From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 From: "Stewart " Subject: Req for help in effect of Caffeine on Developing Nuclei Organization: Medicine Message-ID: <01bc2651$b6b5b760$0100007f@default> X-Newsreader: Microsoft Internet News 4.70.1155 Newsgroups: bionet.neuroscience Date: Sat, 01 Mar 1997 11:55:22 -0800 Path: biosci!agate!howland.erols.net!cam-news-hub1.bbnplanet.com!cpk-news-hub1.bbnplanet.com!news.bbnplanet.com!news.sprintlink.net!news-peer.sprintlink.net!news-pull.sprintlink.net!news.sprintlink.net!news-chi-13.sprintlink.net!news.msn.com!ubtgmsna03!ubtgmsnb02 Lines: 9 I am attempting to find good source information on the effects caused by caffeine on nuclei (especially respiratory) during foetal development, with most interest in any damage/changes caused in the last trimester. If anyone can offer any information, or even assistance in finding the information, I would be most grateful. From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!rutgers.rutgers.edu!uwm.edu!newsfeeds.sol.net!news.maxwell.syr.edu!dispatch.news.demon.net!demon!fido.news.demon.net!demon!sun4nl!news.iaf.nl!news From: J.Nauta@uni4nn.iaf.nl (Jan Nauta) Newsgroups: bionet.neuroscience Subject: Re: "Brain freeze"? Date: Sun, 02 Mar 1997 10:53:05 GMT Organization: Internet Access Foundation Message-ID: <3318505f.15709002@news.gn.iaf.nl> References: <331700A0.1A00@worldnet.att.net> <0n5pst200YUg01h2c0@andrew.cmu.edu> <5f849t$4c8@vixen.cso.uiuc.edu> NNTP-Posting-Host: line17.gn.iaf.nl X-Newsreader: Forte Free Agent 1.1/32.230 Lines: 25 hharris@cs.uiuc.edu (Harlan Harris) wrote: >In article <0n5pst200YUg01h2c0@andrew.cmu.edu>, >Alexander R Terrill wrote: >>>Can anyone tell me what mechanism causes the rapid, brief headache pain >>>when a cold substance is ingested quickly? >> >>It is not the brain that is sensing the pain... >>It has something to do with paranasal air sinuses. > >Hm. What I remember hearing is that the cold chills the carotid arteries, >and that the cold blood shocks the lining of the brain, which is what >hurts. Similar location as migraines, but different type of pain, and of >course much shorter. > >So far we've got, what, 5 responses and 5 theories? > > -Harlan > The last one is the correct one. The ice-cream headache occurs aftter swallowing the cold substance. The blood, ascending to the brain through the carotids close to the pharyngeal wall, is suddenly cooled. This temperature change elicits vascular reactions. Jan Nauta Groningen, the Netherlands From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!daresbury!not-for-mail From: Richard Heath Newsgroups: bionet.neuroscience Subject: Fourth Australasian Cognitive Science Conference Date: 2 Mar 1997 21:05:44 -0000 Lines: 250 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <5fcq38$s2d@mserv1.dl.ac.uk> Original-To: John Shawe-Taylor First Call for Papers Fourth Conference of the Australasian Cognitive Science Society September 26-28, 1997 University of Newcastle NSW AUSTRALIA You are cordially invited to attend the Fourth Biennial Conference of the Australasian Cognitive Science Society which will be held at the University of Newcastle, New South Wales, Australia from 26th - 28th September 1997. This conference involves multidisciplinary participation from a broad spectrum of researchers interested in cognitive processes and artificial intelligence from a variety of cognate disciplines, such as Psychology, Philosophy, Computer Science, Neuroscience, Engineering and Human Factors. The Conference emphasises the common interest among these disciplines towards advancing our knowledge of brain/mind function. The Conference will be held in the David Maddison Building of the Faculty of Medicine situated in downtown Newcastle, within five minutes walking distance from shops, restaurants and of course the lovely harbour and surfing beaches, for which Newcastle is famous. Newcastle is situated some 165 km (100 miles) north of Sydney, to which it is connected by freeway (about 2 hours drive), frequent train service and commuter air services. Several modern hotels/motels are located within easy walking distance from the Conference venue and delegates should consider extending their stay by visiting the nearby Hunter Valley vineyards and the picturesque tourist areas at Lake Macquarie and Port Stephens. The conference will consist of Invited speakers, including Professor Michael Arbib from the University of Southern California and Professor William Bechtel from Washington University in St Louis, applied symposia, oral presentations and poster sessions. Delegates can submit either a poster Abstract, or a longer submission for oral presentation. The latter should consist of a completed paper ready for publication in the Conference Proceedings. This paper must not exceed six pages in length, including references and figures and must be submitted in electronic form using any one of the popular word processing packages. The submission should be single spaced and contain just one column per page. Latex/Tex files should be converted to postscript and submitted in that form. Submitted papers should contain: (i) Title (ii) Author(s) and affiliation/address (iii) email address (iv) a short abstract containing no more than 150 words (v) no more than six pages of single-spaced single-column text (vi) tables and figures embedded within the text, not submitted separately. Each paper will be peer reviewed by two reviewers from different fields of Cognitive Science, in order to ensure high quality and originality as well as multidisciplinary relevance. Authors should avoid unnecessary jargon that will reduce the paper's value to researchers from other fields of Cognitive Science. All accepted papers and poster abstracts will be published on a CD-ROM which will be included in the package of information provided upon arrival. Authors can also include software, demonstrations and other hypermedia materials to support their paper. These material will be stored on the CD-ROM if sufficient space is available. Authors can select the font and page size that suits their writing style. The preferred font is Times-Roman 12pt. It is important that papers requiring revision be received by the Conference Technical Committee before the deadline for production of the CD-ROM. Hypermedia supplementary files should also be submitted by this deadline. Papers not resubmitted in time will only have their abstract published and will revert to poster presentations. Authors should submit their papers and/or poster abstracts in electronic form by email to: Associate Professor Richard Heath rheath@HIPLAB.NEWCASTLE.EDU.AU no later than 16th May 1997. Following review, all resubmitted papers will be due no later than 15th August, 1997. Further inquiries about the conference, including suggestions for Symposia and other aspects of the Conference organisation, should be directed to Professor Heath. Registration Fees (in Australian dollars, A$ = 0.77US$), which include morning and afternoon teas and the Conference CDROM, are: $155 (before 31st July 1997) $70 Students (before 31st July 1997) $175 (after 31st July 1997) $80 students (after 31st July 1997) The Conference Dinner will be held at the newly renovated and historic Customs House restaurant and will be held on Friday 26th September, 1997. The cost is $60 per person for Entree, Main course, Dessert and drinks. If you have any special dietary requests please indicate these on the Registration Form. Cheques/Money Orders payable to Cognitive Science Conference 1997 in Australian dollars should be sent to: Dr Andrew Heathcote Treasurer, Fourth Conference of the Australasian Cognitive Science Society Department of Psychology University of Newcastle University Drive CALLAGHAN NSW 2308 AUSTRALIA The Conference will be preceded by a full day Symposium on Dynamical Models of Mind, Their Nature, Relations to Computational and Other Models, and Future, to be held on 25th September 1997. This issue is currently 'hot' and with widespread ramifications. Whether the Symposium proceeds separately, or is simply incorporated into the conference meetings proper, will depend on the interest expressed. It is intended that the Symposium consist of invited speakers combined with general discussion of the issues. Expressions of interest can take the form of offers of papers (accepted papers, necessarily very limited, will appear in the Conference Proceedings, as above), offers of posters for a poster session, and offers to attend (simplicitur). Further information can be obtained from Professor Hooker on PLCAH@cc.newcastle.edu.au The Conference Organising Committee are: Associate Professor Richard Heath (Psychology) Professor Cliff Hooker (Philosophy) Dr Andrew Heathcote (Psychology) Dr Brett Hayes (Psychology) Associate Professor Graham Wrightson (Computer Science) Dr Bruce Penfold (Electrical Engineering) Dr Peter Pfister (Aviation/Psychology) REGISTRATION FORM Fourth Conference of the Australasian Cognitive Science Society Name: ..................................................................... Title(Dr etc): ........................................... Preferred Name for Badge: ................................................ Mailing Address: Telephone Number: Fax Number: Email address: Please note that all correspondence, wherever possible, will be via email. Cognitive Science Conference Registration (including Society Membership valid until 1999 and a mcopy of the Conference Proceedings on CD-ROM) $155 (before 31st July 1997) ............................ $70 Students (before 31st July 1997) ............................ $175 (after 31st July 1997) ............................ $80 students (after 31st July 1997) ............................ (Students should be include a note on their University's letterhead indicating their status, in order to obtain the special Student rate) Dinner ......... persons @ $60 = .................... Dynamical Models of Mind Workshop I would be interested in attending the above Workshop on 25th September 1997 with Registration costs as follows: YES NO $50 (before 31st July 1997) ....................... $30 Students (before 31st July 1997) ....................... $60 (after 31st July 1997) ....................... $35 students (after 31st July 1997) ....................... If YES, indicate whether you would wish to present a Paper or Poster and send an abstract of 150 words for the Poster or a paper using the same format as for the Cognitive Science Conference. Paper ........... Poster .............. TOTAL .................... Please send a cheque for the above TOTAL amount payable to: Dr Andrew Heathcote Treasurer, Fourth Conference of the Australasian Cognitive Science Society Department of Psychology University of Newcastle, University Drive CALLAGHAN NSW 2308 AUSTRALIA If you are an overseas delegate, please send a bank cheque drawn on an Australian Bank for the above TOTAL amount in Australian dollars. Do you have any special dietary requirementsfor the Conference Dinner? Yes No If YES, please indicate what these are: Accommodation Requirements (Please rank in order of preference): Noahs on the Beach Standard $94.50 Single/Double $10 extra person .............. Ocean View $112.50 Single/Double .............. Radisson Hotel $119 with breakfast Single .............. $129 " " Twin/Double .............. Novocastrian $95 up to $145 for a suite .............. Other hotels and motels are available away from the beach area at reduced rates, approx $50 - $80 We will also endeavour to cater for students and others on limited budgets, if you can let us know your requirements in the space below. Please return this form by email to rheath@hiplab.newcastle.edu.au A World-Wide-Web page is under construction and a more detailed description of the Conference and Workshop will be presented there. From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!agate!howland.erols.net!worldnet.att.net!cpk-news-hub1.bbnplanet.com!news.bbnplanet.com!rill.news.pipex.net!pipex!usenet.eel.ufl.edu!news-feed-1.peachnet.edu!news.service.emory.edu!noel.pd.org!betty From: Betty Martini Newsgroups: bionet.neuroscience Subject: Letter to NutraSweet, Mr. Nelson (fwd) Date: Sun, 2 Mar 1997 16:00:22 -0500 Organization: Emory University Lines: 278 Message-ID: NNTP-Posting-Host: noel.pd.org Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII To: Dave Rietz Thought neurology would like to read what NutraSweet calls tests in safety on aspartame Especially, since the majority of all symptoms and diseases triggered by NutraSweet are neurological - as it destroys the central nervous system.. Regards, Betty ***************************************************************************** To get more information on aspartame, email betty@pd.org as follows: Subject: sendme help The subject line must be typed exactly like the above line. Betty Martini 1. Take the 60-day No-Aspartame test Mission Possible and send us your case history. 5950-H State Bridge Rd 2. Tell your doctor and your friends. Suite 215 3. Return Aspar-Poisoned foods to the store. Duluth GA 30155 USA (Nutrasweet(tm), Equal(tm), Spoonful(tm), etc) Visit http://www.dorway.com with links to more than 25 other Web Sites We are dedicated to the proposition that we will not be satisfied until death and disability are no longer considered an acceptable cost of business. ---------- Forwarded message ---------- Date: Fri, 28 Feb 1997 15:23:00 -0500 (EST) From: Betty Martini Subject: Letter to NutraSweet, Mr. Nelson Dear Mr. Nelson: Mr. R. B. Jones forwarded me your email to him. I'm amused. Don't you realize yet that the propaganda of the NutraSweet Co. has been exposed all over the world. You say I ignore the numerous controlled, peer-reviewed and published scientific studies that have shown safety. I would say this is a very misleading sentence. Let me put it to you as expressed on 60 Minutes by Dr. Walton. "Only the studies funded by the manufacturer (orig Searle)showed safety, yet out of 90 independent studies on aspartame 83 of them showed problems." According to a letter from the FDA to Barbara Mullarkey, all studies that approved NutraSweet were funded by Searle. Should we take any of these manufacturer funded studies seriously? On Dec 8, l975 stockholders filed a class action lawsuit alleging that G. D. Searle had concealed information from the public regarding the nature and quality of animal research at G.D. Searle in violation of the Securities and Exchange Act (Farber l989). A few conclusions of the FDA Task Force: "At the heart of FDA's regulatory process is its ability to rely upon the integrity of the basic safety data submitted by sponsors of regulated products. Our investigation clearly demonstrates that, in the (case of the ) G. D. Searle Co., we have no basis for such reliance now." "We have noted that Searle has not submitted all the facts of experiments to FDA, retaining unto itself the unpermitted option of filtering, interpreting, and not submitting information which we would consider material to the safety evaluation of the product...Finally, we hae found instances of irrelevant or unproductive animal research where experiments have been poorly conceived, carelessly executed or inaccurately analyzed or reported." A few of the relevant findings summarized from various documents describing the FDA Task Force Report: a. "Excising masses (tumors) from live animals, in some cases without histologic examination of the masses, in others without reporting them to the FDA." (US Senate 1976b, page 4) Searle's representatives, when caught and questioned on these irregularities, stated that "these masses were in the head and neck areas and prevented the animals from feeding." "Failure to report to the FDA all internal tumors present in the experimental rats, e.g., polyps in the uterus, ovary neoplasm's as well as other lesions." US Senate 1987, page 437). b. G. D. Searle "stored animal tissues in formaldehyde for so long that they deteriorated." (Gordon l987) c. "Instead of performing autopsies on rhesus monkeys that suffered seizures after being fed aspartame, the company had financed a new monkey seizure study with a different methodology that showed no problems." (Gordon l987) d. "Reporting animals as unavailable for necropsy when, in fact, records indicate that the animals were available but SEarle choose not to purchase them." (US Senate 1976b, page 5) e. Animals which had died were sometimes recorded as being alive and vice versa. "These include approximately 20 instances of animals reported as dead and then reported as having vital signs normal again at subsequent observation periods." (Congressional Record l985b, page S10836) (Really, Mr. Nelson, do you really think the public is going to take seriously studies where rats were resurrected on paper. Try that trick on some of the people who died from NutraSweet like Joyce Wilson, Patricia Craine and William Randolph, etc., etc. For shame!) f. "Selecting statistical procedures which used a total number of animals as the denominator when only a portion of the animals were examined, thus reducing the significance of adverse effects." (US Senate l976b, page 4) j. "In each study investigated, poor practices, inaccuracies, and discrepancies were noted in the antemortem phases which could compromise the study." (Congressional Record l985b, page S10836) k. "Presenting information to FDA in a manner likely to obscure problems, such as editing the report of a consulting pathologist... Reporting one pathology report while failing to submit, or make reference to another usually more adverse pathology report on the same slide." (US Senate l976b, page 4-5) FDA Toxicologist and Task Force member, Dr. Adrian Gross as quoted in the Congressional Record (l985b, page S10826): "They (G. D. Searle) lied and they didn't submit hte real nature of their observations because had they done that it is more than likely that a great number of these studies would have been rejected simply for adquacy. What SEarle did, they took great pains to camouflage these shortcomings of the study. As I say filter and just present to the FDA what they wished the FDA to know and they did other terrible things for instance, animals would develop tumors while they were under study. Well they would remove these tumors from the animals." FDA Lead Investigator and Task Force Team Leader, Phillip Brodsky described the l975 FDA Task Force members as some of the most experienced drug investigators. He went on to state that he had never seen anything as bad as G. D. Searle's studies (Graves l984). The FDA Commissioner at the time, Alexander Schmidt stated (Graves l984): "(Searle's studies were) incredibly sloppy science. What we discovered was reprehensible." Dr. Marvin Legator, professor and director of environmental toxicology at the University of Texas and the pioneer of mutagenicity testing at the FDA from l962 to l972 was asked by Common Cause Magazine to review the FDA investigation results of G. D. SEarle's tests (Graves l984): "(All tests were) scientifically irresponsible and disgraceful. I'm just shocked that that kind of sloppy work would even be sent to FDA, and that the FDA administrators accepted it. There is no reason why these tests couldn't have been carried out correctly. Its not that we are talking about some great scientific break through in methodology." Shall I go on about these studies that showed the safety of aspartame, Mr. Nelson? Shall we discuss that U.S. Attorney Sam Skinner was even asked to indict Searle for fraud but instead switched sides and went to work for the manufacturer's law firm defending the case???? You tell Mr. Jones: "let me reassure you that more than 200 scientific studies have established the safety of aspartame." In testimony before the U.S. Senate, Dr. Jacqueline Verrett, senior scientist on the FDA review team explained these studies were built on a foundation of sand, were worthless and should be thrown out. And you dare to try and make the world believe these studies established safety. I love this sentence: "FDA's approval has been supported by the American Medical Association and many other regulatory agencies around the world." My, my, Mr. Nelson, you forgot to mention the Board of Inquiry of the FDA said not to approve NutraSweet, and the only reason it was approved is that Dr. Arthur Hull Hayes OVERRULED THE BOARD OF INQUIRY, as FDA Commissioner and then went to work for the manufacturer's PR firm! I remind you of 60 Minutes mention of the REVOLVING DOOR! And do tell the public how many millions the NutraSweet Company (Monsanto) have given to the AMA!!! And this discussion of "counter-placebo effect" because people get well when they get off NutraSweet. In other words, get off poison, get well and your brain did it. A burglar could think of a better alibi!!!!! Below is another recent result of the "take the 60 day no aspartame test". Would you believe, another "counter-placebo effect"??? Let's see now she says on abstaining from NutraSweet she has "no more migraine headaches, no leg cramps, joint pain at least 95% gone, skin lesions going way, and she lost 6 1/2 lbs without changing eating habits." Isn't it interesting that no one gets their symptoms back again unless they accidently get more NutraSweet. And they just keep flooding in. Counter-placebo effect, indeed. A brochure on NutraSweet was put out over a year ago in this city warning people of the dangers. It was given out free by the thousands and the thousands. The owner called and said: "You won't believe what is happening?!" I already knew before she told me, people were getting off aspartame and waking up well, big time. Those who were losing their vision could see again, those suffering with the horrible joint pain that aspartame causes found their pain was gone, those who could not walk, now could, and on and on. Why Mr. Nelson, you just couldn't count the "counter-placebo effects" there were so many. And you talk about because the people get on anti-oxidants, etc. When they realize their medical problems have disappeared they want to detoxify and try and get rid of some of the built up formaldehyde and other toxic breakdown products. What you call anecdotal used to be considered clinical observation. Aspartame is a neurotoxin, and you know it. No amount of propaganda will change that, and if this note wasn't already too long, I'd go into some of the other horrors. There are so many problems triggered by aspartame it would take a volume of books to discuss them all. Maybe thats why the FDA listed "92" documented symptoms on aspartame from coma and blindness to four different types of seizures and death! Betty Martini ***************************************************************************** To get more information on aspartame, email betty@pd.org as follows: Subject: sendme help The subject line must be typed exactly like the above line. Betty Martini 1. Take the 60-day No-Aspartame test Mission Possible and send us your case history. 5950-H State Bridge Rd 2. Tell your doctor and your friends. Suite 215 3. Return Aspar-Poisoned foods to the store. Duluth GA 30155 USA (Nutrasweet(tm), Equal(tm), Spoonful(tm), etc) Visit http://www.dorway.com with links to more than 25 other Web Sites We are dedicated to the proposition that we will not be satisfied until death and disability are no longer considered an acceptable cost of business. ---------- Forwarded message ---------- Date: Sun, 23 Feb 1997 To: betty@pd.org Subject: Update from Becky Dear Betty, You requested that I give you an update after 60 days without Aspartame. I have made some progress. I have no more migraine headaches, no leg cramps, the joint pain is at least 95% gone, the skin lesions are going away, and I have lost 6 1/2 pounds without changing my eating habits any more. Something else has happened that I can't explain. For years I have not been able to drink tea because it hurt my lower back (which I thought was my kidneys). When I bought the cali tea for detoxification, I didn't think about that not bothering me. After I had been drinking it for at least 2 weeks, it occurred to me that I wasn't having any pain from drinking tea. Could it be because I'm not consuming aspartame anymore? Anyway, I've been drinking tea now at fast food places instead of diet coke and getting by with it. I could not even sneak in one glass of it before without it causing me pain right away. I have a long way to go but I didn't get this way in two months and I won't get rid of it in two months. It took me 14 years to get this bad and I will keep trying. I have reached a lot of people and hope they will listen. I want to get enough better that when I tell someone about this, they will listen and take notice of my getting better. As of the first of April, we will be going to N. Ft. Myers to live for a couple of months. You can continue to reach me through my daughter's internet address I think you asked in one of your letters if my daughter's name was Frosty...it's Jan. You have my permission to use this information as you see fit. I would like to use the money that it cost over the years for tests and medication for this cause like Dave Reitz has, but my husband is retired and we're on a fixed income. I have a real big family and a lot of friends and will do my best in spreading the word and hope it doesn't fall on deaf ears. If you have time, I'd LOVE to hear from you again. A friend, Becky A Note from her daughter, Jan: Betty, mom didn't mention these other improvements: Her balance seems better at times. Several have noticed that her handwriting is better - isn't as shaky. Her last eye exam, only 1 of her eyes had changed. I don't know if it got better or worse and she didn't ask. She did say that with her double vision that she saw 2 distinct items where now the two overlap again. We keep praying for a miracle. Have you ever heard of anyone slowly regaining what they have lost through the use of aspartame? I want her to get better so much but am also thankful for her not to keep getting worse (which she was before she got off of aspartame). I hope you have time to send a small word of encouragement. She needs it. Thanks for all you've done and continue to do spreading the word. Jan. From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!rutgers.rutgers.edu!uwm.edu!cs.utexas.edu!howland.erols.net!cam-news-hub1.bbnplanet.com!cpk-news-hub1.bbnplanet.com!news.bbnplanet.com!mindspring!cssun.mathcs.emory.edu!news.service.emory.edu!noel.pd.org!betty From: Betty Martini Newsgroups: bionet.neuroscience Subject: FDA "PIVOTAL" SAFETY STUDY: ASPARTAME CAUSED BRAIN SEIZURES, published in THE MILKWEED, Nov. l996 PERMISSION TO REPRINT GIVEN BY , EDITOR, PETE HARDIN, THE MILKWEED, P. O. BOX 10, BROOKLYN, WISCONSIN , 53521 Date: Sun, 2 Mar 1997 14:04:30 -0500 Organization: Emory University Lines: 163 Message-ID: NNTP-Posting-Host: noel.pd.org Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII This information is of particular interest to those concerned with the bovine growth hormone. The only point it doesn't go into is that the phenylalanine in aspartame is genetically engineered. You can get this from the web page on aspartame (MIWON) http://www.ktnet.co.kr/edl/catalog/food/intro-miwon.html Look for the manufacturing process and note how its done, and notice the E. coli under fermentation. The phenylalanine is genetically engineered in E. coli bacteria. Here is the article and Pete Hardin, owner of the Milkweed asks that it be reprinted as a warning to the world. FDA PIVOTAL SAFETY STUDY: ASPARTAME CAUSED BRAIN SEIZURES by Pete Hardin "Despite approval by the federal Food and Drug Administration as a sweetener, Aspartame remains the focus of serious human health questions poised by a core of skeptics. Aspartame is the generic name for "NutraSweet", which is owned by Monsanto Corp. FDA okayed Aspartame for limited food use in the early l980s. In June 1996, FDA sanctioned use of Aspartame in thousands of food products. Aspartame consists of three components: 50% phenylalanine (a chemical which transmits impulses in the human brain), 40% aspartic acid and 10% methanol (wood alcohol-a poison). FDA's human "safety" determination for Aspartame is based upon some 112 studies submitted to FDA by the original manufacturer, Searle Pharmaceuticals. (Monsanto acquired Searle Pharmaceuticals in the mid-1980s.) Of those 112 studies, FDA designated 15 studies "pivotal". Critics have been relooking those "pivotal" studies and come away puzzled how FDA can deduce human "safety". Take, for example, one of the 15 "pivotal" studies: "52 Week Oral Toxicity Infant Monkey Study (SC-18862)." This study orally dosed Aspartame to seven infant Rhesus monkeys for 52 weeks, in work conducted at the University of Wisconsin Medical Center at Madison, Wisconsin. The work was reported in l972. The monkeys were divided in three groups: a low dose group (1.0 g/kg), a medium dose group (3.0 g/kg.) and a high dose group (4-6 g/kg). Aspartame was incorporated into milk formula and administered orally. The high dose group did not consume intended levels of aspartame during the study, perhaps due to the overt sweetness (200 times greater than sugar). Thus, researchers concluded, the high-dose group actually ingested approximately as much Aspartame as the medium-dose group. (Editor's note: The UW-Madison researcher, H. A. Waisman, deceased in mid-study. For that reason, the low-dose group monkeys was pulled from this study at about 200 days-prior to when brain seizures commenced for the medium and high-dose groups.) There was no control group. That ostensible inadequacy in the research protocol was dismissed by the lack of available monkeys and "..limitations in adequately skilled laboratory personnel..." All medium and high dose monkeys showed increased phenylalanine levels in their blood. All medium and high dose monkeys exhibited brain seizures, starting about seven months into the experiment. The study reported "All animals in the medium and high dosage groups exhibited seizure activity. Seizures were observed for the first time following 218 days of treatment... The seizures were of the grand mal type... One monkey, m38, of the high dose group, died after 300 days of treatment. The cause of death was not determined..." Data for the deceased monkey were lost. The study correlates brain seizures with high amounts of phenylalanine ingested by the monkeys. The study determined: "following the end of the experiment, medium and high dose monkeys were kept under observation for three months. No further convulsions were detected during this period." In other words, once the Aspartame was withdrawn from the monkeys' diets, the brain seizures ceased. How could FDA claim a "pivotal" study, in which all of the medium and high dose monkeys suffer brain seizures, confirms Aspartame's safety for humans? Robert Cohen, a private citizen from Oradell, New Jersey (who has a degree in pharmakinesology - brain chemistry), recently un earthed this "pivotal" study. Cohen's personal theory: the milk-based formula in which the monkeys were served their Aspartame in this study is a key link why the brain seizures were suffered. Cohen contends that ingesting dairy products elevates the pH of the stomach. He asserts that drinking a 12 oz. glass of milk buffers the pH of the human stomach from 2 to 6. At a pH of 6, Cohen contends, simple proteins such as Aspartame pass through undigested. Thus, they move to the blood stream intact. (Editor's note: Cohen claims the same phenomenon explains why IGF-1 (insulin-like Growth Factor- -- a potent mitogen, i.e., cancer causing agent) from rbGH-derived milk survives digestion and enters the human bloodstream). Recently, a long term Aspartame critic rolled out a new data analysis, suggesting that Aspartame was a factor in increased incidents of human brain lesions. Monsanto spokesperson Dr. Robert Moser countered that claim, saying that Aspartame was not ingested and did not enter the blood stream. The data revealed by this "pivotal" study submitted to FDA renders false Moser's assertion that Aspartame does not enter the bloodstream. Elevated levels of phenylalanine in the blood of monkeys fed medium and high levels of Aspartame prove that the compound is absorbed into the blood stream. The brain seizures followed. What is the significance of this issue for dairy? NutraSweet is increasingly used in dairy products. At worst, presence of dairy products increases the odds that Aspartame can be channeled through the stomach into the bloodstream, by buffering the stomach's acidity. Word is that CBS' television's hard-hitting news program, "60 Minutes" is preparing a segment on the Aspartame controversy, tentatively due for broadcast on December 29. (was shown) (Editor's Note: We were told recently that an adhesives applications firm in Texas is working on a project to include Aspartame on the back of U.S. Postal Service stamps, to make the stamps which consumers lick "taste better") SWEET NIGHTMARES!" Page continues: ANTI-ASPARTAME CONSUMER GROUP OFFERS INFORMATION TO PUBLIC "A consumer group, Mission Possible, has requested that FDA withdraw Aspartame from public use, in light of the obvious negative health effects depicted in the "pivotal" study described above. The blood data shows the chemical entered the Rhesus monkeys' blood streams. All monkeys receiving medium and high doses of Aspartame suffered severe brain seizures after about seven months' treatments. Persons wishing to receive more information about Aspartame should write Mission Possible at the following address and include 5 32 cent postage stamps to cover return postage. The address is: Mission Possible, 5950 H State Bridge Road, Suite 215, Duluth, Georgia 30155" END OF MILKWEED ARTICLE Betty Martini, Founder Mission Possible Worldwide We ask that this be distributed as a press release, reprinted and put on web to counteract misinformation put out by the NutraSweet Company. On Dave Reitz web page of 117 pages on aspartame he has the brochure put out with the misinformation, answered by Mark Gold. Mark Gold has the largest web page on aspartame which is http://www.tiac.net/users/mgold.health.html Dave Rietz site now links to 29 other web sites on the dangers of aspartame including Dr. H. J. Roberts web page on publications, or you can call 1 800 -814-9800. Doctors writing request a "doctor's packet" with $3.00 priority postage and studies, FDA report, etc. will be sent free of charge. It will include Dr. Roberts position papers which can be distributed to patients on aspartame effects on the central nervous system (mimicking MS), the eyes, diabetes, the heart, etc. Please also put this information in other newsgroups. ***************************************************************************** To get more information on aspartame, email betty@pd.org as follows: Subject: sendme help The subject line must be typed exactly like the above line. Betty Martini 1. Take the 60-day No-Aspartame test Mission Possible and send us your case history. 5950-H State Bridge Rd 2. Tell your doctor and your friends. Suite 215 3. Return Aspar-Poisoned foods to the store. Duluth GA 30155 USA (Nutrasweet(tm), Equal(tm), Spoonful(tm), etc) Visit http://www.dorway.com with links to more than 25 other Web Sites We are dedicated to the proposition that we will not be satisfied until death and disability are no longer considered an acceptable cost of business. From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!agate!howland.erols.net!torn!kone!news.ccs.queensu.ca!not-for-mail From: 3btc@qlink.queensu.ca (Chung Bryan T) Newsgroups: bionet.neuroscience Subject: LEarning from neuro Date: 2 Mar 1997 18:15:14 GMT Organization: Queen's University, Kingston Lines: 5 Message-ID: <5fcg3i$jje@knot.queensu.ca> NNTP-Posting-Host: qlink.queensu.ca X-Newsreader: TIN [UNIX 1.3 950824BETA PL0] Funny, as a biology student hoping to get into the neurosciences, I have just as hard a time breaking into the engineering field. =) Bryan From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!rutgers.rutgers.edu!uwm.edu!newsfeeds.sol.net!europa.clark.net!cpk-news-hub1.bbnplanet.com!cam-news-hub1.bbnplanet.com!news.bbnplanet.com!howland.erols.net!newsxfer.itd.umich.edu!uunet!in2.uu.net!151.112.2.1!mail.llu.edu!not-for-mail From: "Hua \"Howard\" Liu" Newsgroups: bionet.neuroscience Subject: Help wanted: HPLC for CSF analysis Date: 2 Mar 1997 07:58:53 GMT Organization: A poorly-installed InterNetNews site Lines: 16 Message-ID: <01bc26df$9394db60$20027097@SARA.sc.llu.edu> NNTP-Posting-Host: 151.112.2.32 X-Newsreader: Microsoft Internet News 4.70.1155 Hello there! I'm trying to quantify monoamine metabolites (5-HT, 5-HTP, 5-HIAA and 3-OMD, DA) in human ventricular CSF. But there're huge peaks of unknow substances in CSF that make the HPLC system inundated. The system I'm using is ESA Coulochem II HPLC system interfaced with ESA 1090A EC coulometric redox detectors. The columns are 15 cm, 5 micron ESA C-18 reverse phase columns. The mobile phase is a potassium phosphate buffer made by ESA (MD-TM mobile phase). Could anybody help me figure out how to get rid those inundating peaks? It could be proteins, but after tried different concentrations of PCA the peaks are still there. Please, please help me! Thanks in advance. Howard From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!rutgers.rutgers.edu!uwm.edu!cs.utexas.edu!howland.erols.net!ix.netcom.com!news From: flefever@ix.netcom.com(F. Frank LeFever) Newsgroups: bionet.neuroscience Subject: Re: "Brain freeze"? Date: 2 Mar 1997 04:02:12 GMT Organization: Netcom Lines: 60 Message-ID: <5fau44$qrd@sjx-ixn8.ix.netcom.com> References: <331700A0.1A00@worldnet.att.net> <5f7j08$6co@life.ai.mit.edu> <5fa2mc$6f@nntp3.u.washington.edu> NNTP-Posting-Host: nyc-ny8-22.ix.netcom.com X-NETCOM-Date: Sat Mar 01 8:02:12 PM PST 1997 In <5fa2mc$6f@nntp3.u.washington.edu> jtho@neuron.neurosurgery.washington.edu (Joseph T. Ho) writes: > >The last brain surgery I assisted on a few weeks ago, I don't remember any >local anestheic being applied to the meninges. The patient is given a general >anesthetic before the surgery begins and then is given a local along the line >of incision for the scalp. I'm not sure why a local isn't necessary for the >meninges. I think I'll ask next week... > >Oh yeah, I'm not a doctor yet either. :) There's more than one kind of doctor, and I'm not THAT kind, but I'm ONE kind. A guess re (if you say so) lack of pain from cutting meninges: maybe responsive only to stretching, not cutting? I seem to recall reading MANY years ago that the same was true re cutting vs. stretching intestines. F. Frank LeFever, Ph.D. New York Neuropsychology Group > >---------------------------------------------------------------------- ----- >Joseph T. Ho, MS I jtho@u.washington.edu >School of Medicine University of Washington >---------------------------------------------------------------------- ----- > >Daniel Pouzzner (douzzer@mit.edu-antispam) wrote: > >: I'll take a swing at this. > >: Intracranial pain is a regular part of life. The pain signals >: originate in the meninges, which are several protective layers >: sandwiched between the brain and the cranium. In brain surgery, local >: anasthetic is injected into the meninges before an incision is made, >: or perhaps general ansthetic is used at first and local anasthetic is >: injected after the incisions are made, but before the patient returns >: to consciousness (I am Not A Doctor). > >: -Daniel Pouzzner > > > From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!rutgers.rutgers.edu!uwm.edu!news-peer.gsl.net!news.gsl.net!ix.netcom.com!news From: flefever@ix.netcom.com(F. Frank LeFever) Newsgroups: bionet.neuroscience Subject: Re: How can an engineer learn from neuroscientists Date: 2 Mar 1997 03:53:32 GMT Organization: Netcom Lines: 68 Message-ID: <5fatjs$hk8@dfw-ixnews12.ix.netcom.com> References: <5f835o$24ba$1@news-s01.ny.us.ibm.net> NNTP-Posting-Host: nyc-ny8-22.ix.netcom.com X-NETCOM-Date: Sat Mar 01 9:53:32 PM CST 1997 In mitchm@netzone.com (Mitchell Gil Maltenfort) writes: > >I joined the New York Academy od Sciences, because membership permits me I posted a reply suggesting a look at Academy's webpage re advice on organizing a conference, but now want to heartily endorse the reply below, re Society for Neuroscience. Amng the thousands of posters at the SFN meeting in November, I spotted more than a few which you might find of interest; more importantly, they would lead you to people doing the kind of work you want to encourage and to follow. Possibly you can get a copy of program (one volume) and abstracts (three volumes). Try: http://www.jneurosci.org This is for the Society's journal, online, but it probably has a link to the main page, email address, etc. (might be http://www.sfn.org, but not sure of my memory...) Frank LeFever New York Neuropsychology Group >>to get books (annals-this word makes me very unconfortable ) written >>by neuroscientists. Are there more groups of computational neuroscientists There is a huge void between the engineering disciplines and the neurosciences >>and we all lose. >> > > >I can't think of any specific societies dedicated to this work, but you >may want to look at the Society for Neuroscience in which >neurobiological modeling is part of the whole goulash (anything from >channel mechanics to cognitive psychology). > >Texts that I like that took an engineer's approach to neurobiology, and do >a good job of balancing: > >Uwe Windhorst's "How Brain-Like is the Spinal Cord" which is c. 1979, >1980. Springer-Verlag > >R.J. MacGregor's "Neural and Brain Modeling," Academic Press. late 1970's. > >I find that a lot of the 'computational neuroscience' work out there is >very elegant, very ambitious mathematical and computational work which is >clearly inspired by neurobiological fact but has too many simplifications >or assumptions to be considered a definitive explanation for the >neurobiology. > >Good luck, Bernie! From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!rutgers.rutgers.edu!uwm.edu!cs.utexas.edu!howland.erols.net!newsfeed.internetmci.com!metro.atlanta.com!uunet!in3.uu.net!151.99.250.2!server-b.cs.interbusiness.it!usenet From: "Dott. Ivan Tortorici" Newsgroups: bionet.neuroscience Subject: metergolina Date: Sun, 02 Mar 1997 15:51:01 +0100 Organization: Centro Servizi Interbusiness Lines: 1 Message-ID: <331993D5.1F41@telegest.it> NNTP-Posting-Host: 194.243.241.13 Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 2.02Gold (Win95; I) cerco un protocollo di sperimentazione sulla metargolina From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 From: tomw-ingan@msn.com (Thomas Woodworth) Subject: NCV/EMG testing-upper ext. Date: 2 Mar 97 04:13:36 -0800 Message-ID: <00003387+0000157d@msn.com> Path: biosci!ihnp4.ucsd.edu!swrinde!howland.erols.net!worldnet.att.net!cpk-news-hub1.bbnplanet.com!news.bbnplanet.com!news.sprintlink.net!news-peer.sprintlink.net!news-pull.sprintlink.net!news.sprintlink.net!news-dc-9.sprintlink.net!news.msn.com!msn.com Newsgroups: bionet.neuroscience Organization: The Microsoft Network (msn.com) Lines: 6 Occupational Med. clinician beginning screening NCV/EMG testing in industrial setting, interested in good introductory reference material to facilitate learning. Any good, short,, readable journal articles/reviews or textbook chapters out there? Thanks, I needed that. - S.D. From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!agate!howland.erols.net!ix.netcom.com!news From: flefever@ix.netcom.com(F. Frank LeFever) Newsgroups: bionet.neuroscience Subject: Re: "Brain freeze"? Date: 2 Mar 1997 03:12:57 GMT Organization: Netcom Lines: 39 Message-ID: <5far7p$ppa@dfw-ixnews11.ix.netcom.com> References: <331700A0.1A00@worldnet.att.net> NNTP-Posting-Host: nyc-ny8-22.ix.netcom.com X-NETCOM-Date: Sat Mar 01 9:12:57 PM CST 1997 In <331700A0.1A00@worldnet.att.net> CASSIDY-FELTGEN@worldnet.att.net writes: > >Can anyone tell me what mechanism causes the rapid, brief headache pain >when a cold substance is ingested quickly? Related to this is my >question regarding the brain not sensing pain during brain surgery, but >a person's perception of headaches as localized pain within the brain? >Is this a paradox or are headaches not actually occuring within the >brain? Where one "perceives" a pain to be localized is often incorrect, even when dealing with more accessible parts of the body--e.g. an arm or a leg. Pain from ischemic heart muscle (heart attack) might be "perceived" in the arm, etc., etc. You correctly localize headache pain within the HEAD, but there is more in your head than the "brain", if by brain you mean that complex mass of (mostly) nerve cells. I believe the consensus is that the pain is from blood vessels passing through or nearby (perhaps overdistended). The mechanisms of headache DEVELOPMENT, however are complex and poorly understood, and in most cases may involve much brain/blood vessel interaction. The peripheral nervous system and the brain's connections to the periphery may be involved: for example, stimulation of the trigeminal nerve can cause a rapid proliferation of mast cells in the dura (tough tissue covering the brain), and there are complex relationships between mast cells, nitric oxide, dilation of blood vessels, pain, etc. Increased blood flow (in vessels penetrating the brain) in response to mental activity appears mediated mainly by nitric oxide (NO), and I have speculated on the possibility of an "overshoot" of this natural process having pathological effects (e.g. at Society for Neuroscience, Nov. 1996). Frank LeFever New York Neuropsychology Group From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!rutgers.rutgers.edu!uwm.edu!newsfeeds.sol.net!hammer.uoregon.edu!zephyr.texoma.net!uunet!in2.uu.net!204.238.120.21!jump.net!grunt.dejanews.com!not-for-mail Date: Sat, 01 Mar 1997 20:32:11 -0600 From: pavnor97@teleinfo.com.mx Subject: pituitary tumors (chromophobe adneomas) Newsgroups: bionet.neuroscience Message-ID: <857268951.8079@dejanews.com> Reply-To: pavnor97@teleinfo.com.mx Organization: Deja News Usenet Posting Service X-Article-Creation-Date: Sun Mar 02 02:15:51 1997 GMT X-Originating-IP-Addr: 167.114.23.74 () X-Http-User-Agent: Mozilla/1.2b2 (Windows; I; 16bit) X-Authenticated-Sender: pavnor97@teleinfo.com.mx Lines: 11 Looking for information about pituitary tumors, pituitary gland tumors, (hipofisis, craneofaringemas in spanish), solutions, alternatives, neurosurgery, treatment. Tanks, Ricardo. -------------------==== Posted via Deja News ====----------------------- http://www.dejanews.com/ Search, Read, Post to Usenet From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!daresbury!not-for-mail From: Asim Roy Newsgroups: bionet.neuroscience Subject: Does plasticity imply local learning? And other questions Date: 2 Mar 1997 18:12:24 -0000 Lines: 539 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <5fcfu8$i22@mserv1.dl.ac.uk> X-Authentication: none Original-To: neur-sci@dl.ac.uk There is a continuing discussion on the above topic over several mailing lists. I thought neur-sci members might also want to participate in this discussion. So please post. I will compile all responses and post it to the participating mailing lists. ================================================================ I thought it might be productive to the discussion if I compiled and posted the responses I have received so far. I am posting them without any comments. I hope this will promote further discussion on this topic. The original posting is attached below for reference. ============================================================ Response # 1: Re: your note on plasticity and learning Asim, As you mention, neuroscience tends to equate network plasticity with learning. Connectionists tend to do the same. However this raises a problem with biological systems because this conflates the processes of development and learning. Even the smartest organism starts from an egg, and develops for its entire lifespan - how do we distinguish which changes are learnt, and which are due to development. No one would argue that we *learn* to have a cortex, for instance, even though it is due to massive emryological changes in the central nervous system of the animal. This isn't a problem with artificial nets, because they do not usually have a true developmental process and so there can be no confusion between the two; but it has been a long-standing problem in the ethology literature, where learnt changes are contrasted with "innate" developmental ones. A very interesting recent contribution to this debate is Andre Ariew's "Innateness and Canalization", in Philosophy of Science 63 (Proceedings), in which he identifies non-learnt changes as being due to canalised processes. Canalization was a concept developed by the biologist Waddington in the 40's to describe how many changes seem to have fixed end-goals that are robust against changes in the environment. The relationship between development and learning was also thoroughly explored by Vygotsky (see collected works vol 1, pages 194-210). I'd like to see what other sorts of responses you get, Joe Faith Evolutionary and Adaptive Systems Group, School of Cognitive and Computing Sciences, University of Sussex, UK. ================================================================= Response # 2: I fully agree with you, that local learning is not the one and only ultimate approach - even though it results in very good learning for some domains. I am currently writing a paper on the competitive learning paradigm. I am proposing, that this competition that occurs e.g. within neurons should be called local competition. The network as a whole gives a global common goal to these local competitors and thus their competition must be regarded as cooperation from a more global point of view. There is a nice paper by Kenton Lynne that integrates the ideas of reinforcement and competition. When external evaluations are present, they can serve as teaching values, if nor the neurons compete locally. @InProceedings{Lynne88, author = {K.J.\ Lynne}, title = {Competitive Reinforcement Learning}, booktitle = {Proceedings of the 5th International Conference on Machine Learning}, year = {1988}, publisher = {Morgan Kaufmann}, pages = {188--199} } Best regards, Christoph Herrmann ---------------------------------------------------------- Christoph Herrmann Visiting researcher Hokkaido University Meme Media Laboratory Kita 13 Nishi 8, Kita- Tel: +81 - 11 - 706 - 7253 Sapporo 060 Fax: +81 - 11 - 706 - 7808 Japan Email: chris@meme.hokudai.ac.jp http://aida.intellektik.informatik.th-darmstadt.de/~chris/ ---------------------------------------------------------- ============================================================= Response #3: I've just read your list of questions on local vs. global learning mechanisms. I think I'm sympathatic to the implications or presuppositions of your questions but need to read them more carefully later. Meanwhile, you might find very interesting a two-part article on such a mechanism by Peter G. Burton in the 1990 volume of _Psychobiology_ 18(2).119-161 & 162-194. Steve Chandler =============================================================== Response #4: A few years back, I wrote a review article on issues of local versus global learning w.r.t. synaptic plasticity. (Unfortunately, it has been "in press" for nearly 4 years). Below is an abstract. I can email the paper to you in TeX or postscript format, or mail you a copy, if you're interested. Russell Anderson ------------------------------------------------ "Biased Random-Walk Learning: A Neurobiological Correlate to Trial-and-Error" (In press: Progress in Neural Networks) Russell W. Anderson Smith-Kettlewell Eye Research Institute 2232 Webster Street San Francisco, CA 94115 Office: (415) 561-1715 FAX: (415) 561-1610 anderson@skivs.ski.org Abstract: Neural network models offer a theoretical testbed for the study of learning at the cellular level. The only experimentally verified learning rule, Hebb's rule, is extremely limited in its ability to train networks to perform complex tasks. An identified cellular mechanism responsible for Hebbian-type long-term potentiation, the NMDA receptor, is highly versatile. Its function and efficacy are modulated by a wide variety of compounds and conditions and are likely to be directed by non-local phenomena. Furthermore, it has been demonstrated that NMDA receptors are not essential for some types of learning. We have shown that another neural network learning rule, the chemotaxis algorithm, is theoretically much more powerful than Hebb's rule and is consistent with experimental data. A biased random-walk in synaptic weight space is a learning rule immanent in nervous activity and may account for some types of learning -- notably the acquisition of skilled movement. ------------------------------------------ E-mail: send request to rwa@milo.berkeley.edu Slow mail: Russell Anderson 2415 College Ave. #33 Berkeley, CA 94704 ========================================================== Response #5: Asim Roy typed ... > > B) "Pure" local learning does not explain a number of other > activities that are part of the process of learning!! .... > > So, in the whole, there are a "number of activities" that need to > be > performed before any kind of "local learning" can take place. These > aforementioned learning activities "cannot" be performed by a > collection of "local learning" cells! There is more to the process > of learning than simple local learning by individual cells. Many > learning "decisions/tasks" must precede actual training by "local > learners." A group of independent "local learners" simply cannot > start learning and be able to reproduce the learning > characteristics and processes of an "autonomous system" like the > brain. I cannot see how you can prove the above statement (particularly the last sentence). Do you have any proof. By analogy, consider many insect colonies (bees, ants etc). No-one could claim that one of the insects has a global view of what should happen in the colony. Each insect has its own purpose and goes about that purpose without knowing the global purpose of the colony. Yet an ants nest does get built, and the colony does survive. Similarly, it is difficult to claim that evolution has a master plan, order just seems to develop out of chaos. I am not claiming that one type of learning (local or global) is better than another, but I would like to see some evidence for your somewhat outrageous claims. > Note that the global learning mechanism may actually be implemented > with a collection of local learners!! You seem to contradict yourself here. You first say that local learning cannot cope with many problems of learning, yet global learning can. You then say that global learning can be implemented using local learners. This is like saying that you can implement things in C, that cannot be implemented in assembly!! It may be more convenient to implement it in C (or using global learning), but that doesn't make it impossible for assembly. Cheers, Brendan. ------------------------------------------------------------------- Brendan McCane, PhD. Email: mccane@cs.otago.ac.nz Comp.Sci. Dept., Otago University, Phone: +64 3 479 8588. Box 56, Dunedin, New Zealand. There's only one catch - Catch 22. =============================================================== Response #6: In regards to arguments against global learning: I think no one seriously questions this possibility, but think that global learning theories are currently non-verifiable/ non-falsifyable. Part of the point of my paper was that there ARE ways to investigate non-local learning, but it requires changes in current experimental protocols. Anyway, good luck. I look forward to seeing your compilation. Russell ------------------------------------------ E-mail: send request to rwa@milo.berkeley.edu Slow mail: Russell Anderson 2415 College Ave. #33 Berkeley, CA 94704 ============================================================== Response #7: I am sorry that it has taken so long for me to reply to your inquiry about plasticity and local/global learning. As I mentioned in my first note to you, I am sympathetic to the view that learning involves some sort of overarching, global mechanism even though the actual information storage may consist of distributed patterns of local information. Because I am sympathetic to such a view, it makes it very difficult for me to try to imagine and anticipate the problems for such views. That's why I am glad to see that you are explicitly trying to find people to point out possible problems; we need the reality check. The Peter Burton articles that I have sent you describes exactly the kind of mechanism implied by your first question: Does plasticity imply local learning? Burton describes a neurological mechanism by which local learning could emerge from a global signal. Essentially he posits that whenever the new perceptual input being attended to at any given moment differs sufficiently from the record of previously recorded experiences to which that new input is being compared, the difference triggers a global "proceed-to-store" signal. This signal creates a neural "snapshot" (my term, not Burton's) of the cortical activations at that moment, a global episodic memory (subject to stimulus sampling effects, etc.). Burton goes on to describe how discrete episodic memories could become associated with one another so as to give rise to schematic representations of percepts (personally I don't think that positing this abstraction step is necessary, but Burton does it). As neuroscientists sometimes note, while it is widely assumed that LTP/LTD are local learning mechanisms, the direct evidence for such a hypothesis is pretty slim at best. Of course of of the most serious problems with that view is that the changes don't last very long and thus are not really good candidates for long term (i.e., life long) memory. Now, to my mind, one of the most important possibilities overlooked in LTP studies (inherently so in all in vitro preparations and so far as I know--which is not very far because this is not my field--in the in vivo preparations that I have read about) is that LTP/D is either an artifact of the experiment or some sort of short term change which requires a global signal to become consolidated into a long term record. Burton describes one such possible mechanism. Another motivation for some sort of global mechanism comes from the so-called 'binding problem' addressed especially by the Damasio's, but others too. Somehow somewhere all the distributed pieces of information about what an orange is, for example, have to be tied together. A number of studies of different sorts have demonstarted repeatedly that such information is distributed throughout cortical areas. Burton distinguishes between "perceptual learning" requiring no external teacher (either locally or globally) and "conceptual learning", which may require the assistance of a 'teacher'. In his model though, both types of learning are activated by global "proceed-to-learn" signals triggered in turn by the global summation of local disparities between remembered episodes and current input. I'll just mention in closing that I am particularly interested in the empirical adequacy of neuropsychological accounts such as Burton's because I am very interested in "instance-based" or "exemplar-based" models of learning. In particular, Royal Skousen's _Analogical Modeling of Language_ (Kluwer, 1989) describes an explicit, mathematical model for predicting new behavior on analogy to instances stored in long term memory. Burton's model suggests a possible neurological basis for such behavior. ============================================================== Response #8: ******************************************************************* Fred Wolf E-Mail: fred@chaos.uni-frankfurt.de Institut fuer Theor. Physik Robert-Mayer-Str. 8 Tel: 069/798-23674 D-60 054 Frankfurt/Main 11 Fax: (49) 69/798-28354 Germany ******************************************************************* Dear Asim Roy, could you please point me to a few neuroBIOLOGICAL references that justify your claim that > > A predominant belief in neuroscience is that synaptic plasticity > and LTP/LTD imply local learning (in your sens). > I think many people appreciate that real learning implies the concerted interplay of a lot of different brain systems and should not even be attempted to be explained by "isolated local learners". See e.g. the series of review-papers on memory in a recent volume of PNAS 93 (1996) (http://www.pnas.org/). Good luck with your general theory of global/local learning. best wishes Fred Wolf ============================================================== Response #9: Comp-Neuro Mailing List wrote: > > =================================================================== > Date: Sun, 16 Feb 1997 22:57:11 -0500 (EST) > From: Asim Roy > Subject: Does plasticity imply local learning? And other questions > > Any comments on these ideas and possibilities are welcome. > > Asim Roy > Arizona State University I am into neurocomputing for several years. I read your arguments with interest. They certainly deserve further attention. Perhaps some combination of global-local learning agents would be the right choice. - Vassilis G. Kaburlasos Aristotle University of Thessaloniki, Greece ============================================================== =============================================================== Original Memo: A predominant belief in neuroscience is that synaptic plasticity and LTP/LTD imply local learning. It is a possibility, but it is not the only possibility. Here are some thoughts on some of the other possibilities (e.g. global learning mechanisms or a combination of global/local mechanisms) and some discussion on the problems associated with "pure" local learning. The local learning idea is a very core idea that drives research in a number of different fields. I welcome comments on the questions and issues raised here. This note is being sent to many listserves. I will collect all of the responses from different sources and redistribute them to all of the participating listserves. The last such discussion was very productive. It has led to the realization by some key researchers in the connectionist area that "memoryless" learning perhaps is not a very "valid" idea. That recognition by itself will lead to more robust and reliable learning algorithms in the future. Perhaps a more active debate on the local learning issue will help us resolve this issue too. A) Does plasticity imply local learning? The physical changes that are observed in synapses/cells in experimental neuroscience when some kind of external stimuli is applied to the cells may not result at all from any specific "learning" at the cells. The cells might simply be responding to a "signal to change" - that is, to change by a specific amount in a specific direction. In animal brains, it is possible that the "actual" learning occurs in some other part(s) of the brain, say perhaps by a global learning mechanism. This global mechanism can then send "change signals" to the various cells it is using to learn a specific task. So it is possible that in these neuroscience experiments, the external stimuli generates signals for change similar to those of a global learning agent in the brain and that the changes are not due to "learning" at the cells themselves. Please note that scientific facts and phenomenon like LTP/LTD or synaptic plasticity can probably be explained equally well by many theories of learning (e.g. local learning vs. global learning, etc.). However, the correctness of an explanation would have to be judged from its consistency with other behavioral and biological facts, not just "one single" biological phenomemon or fact. B) "Pure" local learning does not explain a number of other "activities" that are part of the process of learning!! When learning is to take place by means of "local learning" in a network of cells, the network has to be designed prior to its training. Setting up the net before "local" learning can proceed implies that an external mechanism is involved in this part of the learning process. This "design" part of learning precedes actual training or learning by a collection of "local learners" whose only knowledge about anything is limited to the local learning law to use! In addition, these "local learners" may have to be told what type of local learning law to use, given that a variety of different types can be used under different circumstances. Imagine who is to "instruct and set up" such local learners which type of learning law to use? In addition to these, the "passing" of appropriate information to the appropriate set of cells also has to be "coordinated" by some external or global learning mechanism. This coordination cannot just happen by itself, like magic. It has to be directed from some place by some agent or mechanism. In order to learn properly and quickly, humans generally collect and store relevant information in their brains and then "think" about it (e.g. what problem features are relevant, complexity of the problem, etc.). So prior to any "local learning," there must be processes in the brain that "examine" this "body of information/facts" about a problem in order to design the appropriate network that would fit the problem complexity, select the problem features that are meaningful, etc. It would be very difficult to answer the questions "What size net?" and "What features to use?" without looking at the problem (body of information)in great detail. A bunch of "pure" local learners, armed with their local learning laws, would have no clue to these issues of net design, generalization and feature selection. So, in the whole, there are a "number of activities" that need to be performed before any kind of "local learning" can take place. These aforementioned learning activities "cannot" be performed by a collection of "local learning" cells! There is more to the process of learning than simple local learning by individual cells. Many learning "decisions/tasks" must precede actual training by "local learners." A group of independent "local learners" simply cannot start learning and be able to reproduce the learning characteristics and processes of an "autonomous system" like the brain. Local learning or local computation, however, is still a feasible idea, but only within a general global learning context. A global learning mechanism would be the one that "guides" and "exploits" these local learners or computational elements. However, it is also possible that the global mechanism actually does all of the computations (learning) and "simply sends signals" to the network of cells for appropriate synaptic adjustment. Both of these possibilities seem logical: (a) a "pure" global mechanism that learns by itself and then sends signals to the cells to adjust, or (b) a global/local combination where the global mechanism performs certain tasks and then uses the local mechanism for training/learning. Thus note that the global learning mechanism may actually be implemented with a collection of local learners or computational elements!! However, certain "learning decisions" are made in the global sense and not by "pure" local learners. The basic argument being made here is that there are many tasks in a "learning process" and that a set of "local learners" armed with their local learning laws is incapable of performing all of those tasks. So local learning can only exist in the context of global learning and thus is only "a part" of the total learning process. It will be much easier to develop a consistent learning theory using the global/local idea. The global/local idea perhaps will also give us a better handle on the processes that we call "developmental" and "evolutionary." And it will, perhaps, allow us to better explain many of the puzzles and inconsistencies in our current body of discoveries about the brain. And, not the least, it will help us construct far better algorithms by removing the "unwarranted restrictions" imposed on us by the current ideas. Any comments on these ideas and possibilities are welcome. Asim Roy Arizona State University From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!agate!howland.erols.net!newsxfer.itd.umich.edu!uunet!in3.uu.net!204.191.213.61!ott.istar!istar.net!tor.istar!east.istar!news1.istar.ca!news From: "PLEASE HELP" Newsgroups: alt.med.phys-assts,bionet.neuroscience,sci.med.immunology,sci.med.pathology,sci.med.pharmacy Subject: Aspergillus Nidulans in the CNS Date: 2 Mar 1997 17:41:07 GMT Organization: Dominion Regalia Lines: 38 Message-ID: <5fce3j$kjt@news.istar.ca> NNTP-Posting-Host: ts14-12.tor.istar.ca X-Newsreader: Microsoft Internet News 4.70.1157 Xref: biosci bionet.neuroscience:18301 sci.med.immunology:9084 sci.med.pathology:4785 sci.med.pharmacy:42590 PLEASE HELP We are the parents of a nineteen month old Baby Boy with a life threatening disease. To our knowledge this is the first case of a fungal infection of this type known anywhere in the world. If you can provide any suggestions for helping our little Boy we would be most grateful. Infection: Aspergillus Nidulans in the Central Nervous System. The fungus surrounds the base of the brain and is present in other locations on the covering of the meninges. This was diagnosed following a biopsy taken from his lumbar region. Biopsy was taken September 13, 1996. Cause of Infection: Unknown Patient's Present condition: Beginning to show signs of Hydrocephalus. Vomiting is becoming more frequent. Febers and pain becoming more frequent and severe. He is developing a little trouble walking. Course of Treatment: Begain treatment in September on Amphotericin B and 4 FC given by IV. Treatment was determined to be unsuccessful. After one month MRI showed disease had progressed. The next treatment was Amphotericin Liposomal given by IV and Oral Itraconazole. An MRI taken one month after this treatment was started, appeared to show a slight reduction in the size of the fungal growths, however a followup MRI taken thirty days later showed the fungus was once again growing. At this point the decision was made to put in a resevoir to administer Ampho B directly into his DSF. On January 9, 1997 a second biopsy was taken from His spine. The biopsy confirmed the fungus was Aspergillus, but the cultures would not grow so it could not be confirmed the fungus was Nidulans. An MRI taken February 3, 1997 has shown that the fungus increased in size considerably even with this treatment and there are new lesions. The therapy is now going to be couble the dose of Oral Itraconazole (10mg/kg) and the Itrathecal Amphotericin therapy has been discontinued. He is going to given Gamma Interferon sub-cutaneiously to boost immune function though no immune deficiency has ever been detected. He had a negative result when tested for CGD. From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!ihnp4.ucsd.edu!swrinde!howland.erols.net!ix.netcom.com!news From: flefever@ix.netcom.com(F. Frank LeFever) Newsgroups: bionet.neuroscience Subject: Re: How can an engineer learn from neuroscientists Date: 2 Mar 1997 03:40:44 GMT Organization: Netcom Lines: 50 Message-ID: <5fasrs$756@sjx-ixn2.ix.netcom.com> References: <5f835o$24ba$1@news-s01.ny.us.ibm.net> NNTP-Posting-Host: nyc-ny8-22.ix.netcom.com X-NETCOM-Date: Sat Mar 01 7:40:44 PM PST 1997 In <5f835o$24ba$1@news-s01.ny.us.ibm.net> junior1@ibm.net [Bernie Arruza] writes: > >Hi, > >I joined the New York Academy od Sciences, because membership permits me >to get books (annals-this word makes me very unconfortable ) written >by neuroscientists. Are there more groups of computational neuroscientists >(like Carver Mead's - California Institute of Technology) OR are there >neuroscientists working with electrical engineers? What do they publish? >Any other societies that could be interesting to me? > >There is a huge void between the engineering disciplines and the neurosciences >and we all lose. > > >___________________________________ >Bernie Arruza. >IBM >Boca Raton, Fl USA >__________________________________ >__The_way_of_the_warrior_is_the___ >__resolute_acceptance_of_death.___ >__________________________________ >___________Miyamoto_Musashi_______ >___________The_Book_of_Five_Rings_ >__________________________________ Have you checked out the Academy's website? Among other things, it gives instructions on how to propose Academy-sponsored conferences, which will eventually be reported in Annals. Do you KNOW of engineers who could collaborate with neuroscientists in organizing such a conference? Put bugs in their ears... http://www.nyas.org Frank LeFever Vice-chair, Linguistics Section, NYAS (past-Chair & current member of Advisory Committee, Psychology Section) From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!agate!howland.erols.net!ix.netcom.com!news From: flefever@ix.netcom.com(F. Frank LeFever) Newsgroups: bionet.neuroscience Subject: Re: neurophtalmo Date: 2 Mar 1997 03:29:01 GMT Organization: Netcom Lines: 34 Message-ID: <5fas5t$2fv@sjx-ixn7.ix.netcom.com> References: <3316CC16.6834@smtp.wanadoo.fr> NNTP-Posting-Host: nyc-ny8-22.ix.netcom.com X-NETCOM-Date: Sat Mar 01 7:29:01 PM PST 1997 In <3316CC16.6834@smtp.wanadoo.fr> Yann Tessier writes: > >Hi, > >I am a vet researcher, but my question is personal. > >I have chronic visual symptoms with no physical evidence neither in neurology, nor in >ophtalmology. > >Could someone of you discuss with me about it or does anyone know a newsgroup of >neurophtalmologists ? > >Thanks for your help. > >Yann Tessier, DVM, France I'm a neuropsychologist who has encountered various unusual visual symptoms in patients, and have studied some more-or-less "visual" neurological phenomena. As a very indirect route, I could perhaps contact colleagues at Hopital Salpetriere (Paris) who might know of a neuroophthalmologist to refer you to IF this is the right level of analysis; maybe behavioral neurologist or neuropsychologist (depending on level of analysis). (Please excuse lack of ^, ^, and accent grave!) Meanwhile, would like to get a hint: what KIND of problems? Examples? Frank LeFever New York Neuropsychology Group From owner-neuroscience@net.bio.net Sat Mar 01 22:00:00 1997 Path: biosci!agate!howland.erols.net!worldnet.att.net!cbgw2.lucent.com!news.bu.edu!usenet From: monikat@bu.edu (Monika Trzcinska) Newsgroups: bionet.neuroscience Subject: Re: Looking for digitized brain slices Date: Mon, 03 Mar 1997 00:20:30 GMT Organization: Boston University Lines: 24 Message-ID: <331a129d.9344552@nntp.bu.edu> References: NNTP-Posting-Host: ppp-93-24.bu.edu X-Newsreader: Forte Free Agent 1.1/32.230 On Tue, 23 May 1995 02:15:23 GMT, dforster@ccs.carleton.ca (David Forster) wrote: >In article >elenam@uxcomp2.iimas.unam.mx (Elena Martinez) writes: >> Does anybody know if there are ftp deposits with images >> containing complete brain slices? Prefereably from rats... >=============================== >David Forster >Department of Psychology >Carleton University Just down the Canal from you, at U.Ottawa, Claude Kateb,PhD, former grad student of Zul Merali, recently produced this information in a markatable format. He took brain slices and scanned them in and saved them on disks using Corel file formats. These import well into Corel Draw, of course, and were more refined in terms of distance from Bregma in all the planes (sagital, coronal, and horizontal), compared to the Paxinos and Watson atlas. Unfortuantely, the latest that we have heard is that the company is no longer solvent. Perhaps, Dr.Merali has information. Monika Trzcinska, Ph.D. & Matthew Simpson From owner-neuroscience@net.bio.net Sun Mar 02 22:00:00 1997 Path: biosci!ihnp4.ucsd.edu!swrinde!cs.utexas.edu!feeder.chicago.cic.net!news.enteract.com!news.maxwell.syr.edu!europa.clark.net!arclight.uoregon.edu!news-m01.ny.us.ibm.net!news-s01.ny.us.ibm.net!not-for-mail From: junior1@ibm.net [Bernie Arruza] Newsgroups: bionet.neuroscience Subject: Re: How can an engineer learn from neuroscientists Date: 3 Mar 1997 02:06:22 GMT Organization: IBM Corp. MTC Boca Raton, Fl U.S.A. Lines: 36 Message-ID: <5fdbmu$189m$1@news-s01.ny.us.ibm.net> References: <5f835o$24ba$1@news-s01.ny.us.ibm.net> Reply-To: junior1@ibm.net [Bernie Arruza] NNTP-Posting-Host: slip129-37-229-82.fl.us.ibm.net X-Newsreader: IBM NewsReader/2 v1.03 In , mitchm@netzone.com (Mitchell Gil Maltenfort) writes: >I find that a lot of the 'computational neuroscience' work out there is >very elegant, very ambitious mathematical and computational work which is >clearly inspired by neurobiological fact but has too many simplifications >or assumptions to be considered a definitive explanation for the >neurobiology. Yes...and that is the problem. Most (?) of the assumptions have not been "blessed" by neuroscientists. As a result, brain scientist don't trust the results obtained and more often than not the results obtained are ignored instead of being challenged and discussed (good old feedback). Universities have very little incentive to merge their departments to study the mysteries of the brain. Corporation are too concerned about the next quarter to take a chance on unproven technologies (those of us in the corporate world have the resources but we lack the incentives and the time). An the true patron of the sciences the military is being cut back to the bone. Unless things change, this train is going to slow down!. We are all waiting for a scientific breakthrough. Wouldn't a technical breakthrough help to improve the odds of success for all of us interested in how the brain functions? ___________________________________ Bernie Arruza. IBM Boca Raton, Fl USA __________________________________ __The_way_of_the_warrior_is_the___ __resolute_acceptance_of_death.___ __________________________________ ___________Miyamoto_Musashi_______ ___________The_Book_of_Five_Rings_ __________________________________ From owner-neuroscience@net.bio.net Sun Mar 02 22:00:00 1997 Path: biosci!rutgers.rutgers.edu!news.sgi.com!news.maxwell.syr.edu!news.cis.ohio-state.edu!magnus.acs.ohio-state.edu!usenet.ins.cwru.edu!slider.bme.ri.ccf.org!kira.cc.uakron.edu!brain!nutty From: nutty@brain (Madhusudan Natarajan) Newsgroups: bionet.neuroscience Subject: Re: "Brain freeze"? Date: 1 Mar 1997 04:02:42 GMT Organization: University of Akron Lines: 25 Message-ID: <5f89p2$lsl@kira.cc.uakron.edu> References: <331700A0.1A00@worldnet.att.net> NNTP-Posting-Host: brain.biomed.uakron.edu X-Newsreader: TIN [version 1.2 PL2] CASSIDY-FELTGEN@worldnet.att.net wrote: : Can anyone tell me what mechanism causes the rapid, brief headache pain : when a cold substance is ingested quickly? Related to this is my : question regarding the brain not sensing pain during brain surgery, but : a person's perception of headaches as localized pain within the brain? : Is this a paradox or are headaches not actually occuring within the : brain? OK, didnt the same question pop up a while ago.. except that it was called brain cramps then? There were a whole host of theories proposed, and then the thread died a natural death. Wonder if there are any archives of all articles posted in the past from where we can dig up all the relevant posts? -- Madhusudan Natarajan ..and still partly at.. Ward 5-223 : Ph (312) 503 0202 Dept. of Physiology Dept. of Biomedical Engineering Northwestern University University of Akron -- "I have no data yet. It is a capital mistake to theorize before one has data. Insensibly one begins to twist facts to suit theories, instead of theories to suit facts." - Sherlock Holmes From owner-neuroscience@net.bio.net Sun Mar 02 22:00:00 1997 Path: biosci!rutgers.rutgers.edu!uwm.edu!news-peer.gsl.net!news.gsl.net!howland.erols.net!vixen.cso.uiuc.edu!s.psych.uiuc.edu!kspencer From: kspencer@s.psych.uiuc.edu (Kevin Spencer) Newsgroups: bionet.neuroscience Subject: Re: How can an engineer learn from neuroscientists Date: 3 Mar 1997 07:58:57 GMT Organization: UIUC Department of Psychology Lines: 40 Message-ID: <5fe0c1$1p2@vixen.cso.uiuc.edu> References: <5f835o$24ba$1@news-s01.ny.us.ibm.net> <5fdbmu$189m$1@news-s01.ny.us.ibm.net> NNTP-Posting-Host: s.psych.uiuc.edu X-Newsreader: NN version 6.5.0 #6 junior1@ibm.net [Bernie Arruza] writes: [snip] >Universities have very little incentive to merge their departments to study the >mysteries of the brain. Excuse me, but you are quite wrong. I guess you don't know that many universities in the past 10 years have been establishing cognitive science and cognitive neuroscience departments and programs. Whole conferences and journals devoted to these new integrative disciplines have sprung up. The 1990s have been proclaimed the "Decade of the Brain" and the fed govt and private foundations have made funding cognitive neuroscience a priority. [snip] >Unless things change, this train is going to slow down!. We are all waiting for >a scientific breakthrough. Wouldn't a technical breakthrough help to improve the >odds of success for all of us interested in how the brain functions? The train is going to slow down? Are you kidding? The train has been speeding up since -- well, IMHO I'd say the 40s (when McCulloch & Pitts introduced a neural network model), and our understanding of the relationships between brain and mind are constantly evolving. This is truly an exciting time to be working in this area. If you want technical breakthroughs, since about 1980 we've had: magnetoencephalography (MEG), EEG/MEG source localization, positron emission tomography, magnetic resonance imaging (MRI) and functional MRI. If you want to talk about modeling -- did you hear about the connectionist "revolution" that started in the mid-80s? That's just a short and skewed very list of the exciting developments that have driven the field recently. (No offense to people working with animal models, I'm not very familiar with those techniques.) Kevin ----------------------------------------------------------- Kevin Spencer Cognitive Psychophysiology Laboratory and Beckman Institute University of Illinois at Urbana-Champaign kspencer@p300.cpl.uiuc.edu ----------------------------------------------------------- From owner-neuroscience@net.bio.net Sun Mar 02 22:00:00 1997 Path: biosci!agate!howland.erols.net!ais.net!news.megsinet.net!not-for-mail From: "Michael J. Roth" Newsgroups: bionet.neuroscience Subject: Betty Martini Lies (was Re: PT for Parkinson's?) Date: 3 Mar 1997 05:20:35 GMT Organization: WebSpun, Ltd. Lines: 14 Message-ID: <01bc2792$c1026780$e54b85d0@ns1.megsinet.net> NNTP-Posting-Host: 225ohiomax2-101.megsinet.net X-Newsreader: Microsoft Internet News 4.70.1160 Betty Martini wrote: > Notice in Senator Metzenbaum's bill the mention that aspartame changes the > dopamine level of the brain, and that it is a drug that interacts with > other drugs. Betty knows you won't bother to check the text of the Metzenbaum bill, but I did. It does not contain the word "dopamine." It does not say that aspartame is a drug. Judge for yourself whether to believe anything she says. Mike From owner-neuroscience@net.bio.net Sun Mar 02 22:00:00 1997 Path: biosci!daresbury!bioftp.unibas.ch!news.vub.ac.be!news.belnet.be!news.rediris.es!news.uoregon.edu!newsfeed.orst.edu!news.nero.net!rutgers.rutgers.edu!news.sgi.com!news.maxwell.syr.edu!newsfeeds.sol.net!newspump.sol.net!ddsw1!news.mcs.net!not-for-mail From: Don Scott Newsgroups: alt.med.phys-assts,bionet.neuroscience,sci.med.immunology,sci.med.pathology,sci.med.pharmacy Subject: Re: Aspergillus Nidulans in the CNS Date: Mon, 03 Mar 1997 13:45:12 -0600 Organization: MCSNet Services Lines: 1099 Message-ID: <331B2A48.36D3@mcs.net> References: <5fce3j$kjt@news.istar.ca> Reply-To: dscott@mcs.net NNTP-Posting-Host: dscott.pr.mcs.net Mime-Version: 1.0 Content-Type: multipart/mixed; boundary="------------342B670CC3D" X-Mailer: Mozilla 3.0Gold (Win95; U) To: PLEASE HELP Xref: biosci bionet.neuroscience:18318 sci.med.immunology:9096 sci.med.pathology:4797 sci.med.pharmacy:42617 This is a multi-part message in MIME format. --------------342B670CC3D Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Having chilkdren, grandchildren and greatgrandchildren, I empathize with you. I did a Medline search that turned up 16 possibly relevant citations with abstracts, which I attach hereto. I do not fully understand it, but there seems to be some genetic similarity betqween key genes in A. nidulans and brain tubulins. Please look at some of the first abstracts but pay particular attentio to record 8 reporting a brain infection, and to record 13. Antimitotic substances may work, but the question is what they will do to the brain. Furthermore they may have to be directly introduced into the spinal fluid, and the hazards of such action may not be known. You may be, in part, a "victim" of the litigious nature of our society, restricting the treating physicians from trying novel procedures. Good luck. Don PLEASE HELP wrote: > > PLEASE HELP > > We are the parents of a nineteen month old Baby Boy with a life threatening > disease. To our knowledge this is the first case of a fungal infection of > this type known anywhere in the world. If you can provide any suggestions > for helping our little Boy we would be most grateful. > > Infection: Aspergillus Nidulans in the Central Nervous System. The > fungus surrounds the base of the brain and is present in other locations on > the covering of the meninges. This was diagnosed following a biopsy taken > from his lumbar region. Biopsy was taken September 13, 1996. > > Cause of Infection: Unknown > > Patient's Present condition: Beginning to show signs of Hydrocephalus. > Vomiting is becoming more frequent. Febers and pain becoming more frequent > and severe. He is developing a little trouble walking. > > Course of Treatment: Begain treatment in September on Amphotericin B and > 4 FC given by IV. Treatment was determined to be unsuccessful. After one > month MRI showed disease had progressed. > The next treatment was Amphotericin Liposomal given by IV and Oral > Itraconazole. An MRI taken one month after this treatment was started, > appeared to show a slight reduction in the size of the fungal growths, > however a followup MRI taken thirty days later showed the fungus was once > again growing. At this point the decision was made to put in a resevoir > to administer Ampho B directly into his DSF. On January 9, 1997 a second > biopsy was taken from His spine. The biopsy confirmed the fungus was > Aspergillus, but the cultures would not grow so it could not be confirmed > the fungus was Nidulans. > An MRI taken February 3, 1997 has shown that the fungus increased in size > considerably even with this treatment and there are new lesions. > The therapy is now going to be couble the dose of Oral Itraconazole > (10mg/kg) and the Itrathecal Amphotericin therapy has been discontinued. > He is going to given Gamma Interferon sub-cutaneiously to boost immune > function though no immune deficiency has ever been detected. He had a > negative result when tested for CGD. -- "Nothing else matters much - not wealth, nor learning, nor even health - without this gift: the spiritual capacity to keep zest in living." Harry Emerson Fosdick --------------342B670CC3D Content-Type: text/plain; charset=us-ascii; name="glaxo5.bat" Content-Transfer-Encoding: 7bit Content-Disposition: inline; filename="glaxo5.bat" Terms of About Physicians' Home Register for Back to Use Page PHP Preview PHP Helix [Helix] [sp.nex[sp.nex[sp.nex[sp.ne[sp.nextform=help/c_srch.htm i] Show records Copyright Information ---------------------------------------------------------------------------- Record 1 of 16 in MEDLINE EXPRESS (R) 1991-1995 TITLE NudF, a nuclear migration gene in Aspergillus nidulans, is similar to the human LIS-1 gene required for neuronal migration. AUTHOR(S) Xiang-X; Osmani-AH; Osmani-SA; Xin-M; Morris-NR ADDRESS OF AUTHOR Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635, USA. SOURCE (BIBLIOGRAPHIC CITATION) Mol-Biol-Cell. 1995 Mar; 6(3): 297-310 Library Holdings Message Press to receive the full text via fax. Call Number Price: $11.50 plus fax surcharge INTERNATIONAL STANDARD SERIAL NUMBER 1059-1524 PUBLICATION YEAR 1995 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION UNITED-STATES ABSTRACT During a study of the genetics of nuclear migration in the filamentous fungus Aspergillus nidulans, we cloned a gene, nudF, which is required for nuclear migration during vegetative growth as well as development. The NUDF protein level is controlled by another protein NUDC, and extra copies of the nudF gene can suppress the nudC3 mutation. nudF encodes a protein with 42% sequence identity to the human LIS-1 (Miller-Dieker lissencephaly-1) gene, which is required for proper neuronal migration during brain development. This strong similarity suggests that the LIS-1 gene product may have a function similar to that of NUDF and supports previous findings to suggest that nuclear migration may play a role in neuronal migration. MINOR MESH HEADINGS Amino-Acid-Sequence; Aspergillus-nidulans-growth-and-development; Aspergillus-nidulans-ultrastructure; Cell-Movement; Cell-Nucleus-physiology; Cell-Polarity; Fungal-Proteins-biosynthesis; Fungal-Proteins-physiology; Gene-Expression-Regulation,-Fungal; Molecular-Sequence-Data; Movement-; Proteins-chemistry; Sequence-Alignment; Sequence-Homology,-Amino-Acid MAJOR MeSH HEADINGS *Aspergillus-nidulans-genetics; *Fungal-Proteins-genetics; *Genes,-Structural,-Fungal CHECKTAGS Comparative-Study; Support,-U.S.-Gov't,-P.H.S. GENE SYMBOL nudF; nudC; LIS-1; nud6; nud7; nudA PUBLICATION TYPE JOURNAL-ARTICLE CAS REGISTRY NUMBER OR EC NUMBER 0; 0; 0; 0; 0 NAME OF SUBSTANCE Fungal-Proteins; LIS1-protein; NUDC-protein; NUDF-protein; Proteins MEDLINE ACCESSION NUMBER 95337460 UPDATE CODE 9510 SECONDARY SOURCE IDENTIFIER GENBANK/U22009 ---------------------------------------------------------------------------- Record 2 of 16 in MEDLINE EXPRESS (R) 1991-1995 TITLE Purification and characterization of assembly-competent tubulin from Aspergillus nidulans. AUTHOR(S) Yoon-Y; Oakley-BR ADDRESS OF AUTHOR Department of Molecular Genetics, Ohio State University, Columbus 43210, USA. SOURCE (BIBLIOGRAPHIC CITATION) Biochemistry. 1995 May 16; 34(19): 6373-81 Library Holdings Message Press to receive the full text via fax. Call Number Price: $17.75 plus fax surcharge INTERNATIONAL STANDARD SERIAL NUMBER 0006-2960 PUBLICATION YEAR 1995 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION UNITED-STATES ABSTRACT We have developed a procedure for purifying assembly-competent tubulin from Aspergillus nidulans. To our knowledge, this is the first report of the purification of assembly-competent tubulin from a filamentous fungus, and the procedure should be of great value in analyzing the large number of alpha- and beta-tubulin mutations that have been isolated and characterized in A. nidulans. Our procedure consists of overproduction of alpha- and beta-tubulin, partial purification by ion-exchange chromatography, and final purification by rounds of assembly and disassembly. We have found that taxol promotes the assembly of A. nidulans tubulin into microtubules, but a higher concentration of taxol is required for maximal assembly of A. nidulans tubulin than is required for brain tubulin. The critical concentration for assembly in the presence of taxol is also significantly higher for A. nidulans tubulin than for brain tubulin. In addition, A. nidulans microtubules that were assembled and maintained in the presence of taxol depolymerized in conditions in which taxol-stabilized mammalian microtubules remain intact. These results suggest that A. nidulans tubulin has a lower affinity for taxol than mammalian tubulin. MINOR MESH HEADINGS Amino-Acid-Sequence; Cattle-; Fungal-Proteins-isolation-and-purification; Microscopy,-Electron; Molecular-Sequence-Data; Paclitaxel-pharmacology; Protein-Binding-drug-effects; Recombinant-Proteins; Sequence-Alignment; Sequence-Homology,-Amino-Acid; Tubulin-metabolism MAJOR MeSH HEADINGS *Aspergillus-nidulans-chemistry; *Microtubules-chemistry; *Tubulin-isolation-and-purification CHECKTAGS Animal; Comparative-Study; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S. GENE SYMBOL tubA; benA PUBLICATION TYPE JOURNAL-ARTICLE CONTRACT OR GRANT NUMBERS GM31837GMNIGMS CAS REGISTRY NUMBER OR EC NUMBER 0; 0; 0; 33069-62-4 NAME OF SUBSTANCE Fungal-Proteins; Recombinant-Proteins; Tubulin; Paclitaxel MEDLINE ACCESSION NUMBER 95275830 UPDATE CODE 9509 ---------------------------------------------------------------------------- Record 3 of 16 in MEDLINE EXPRESS (R) 1991-1995 TITLE Cytoplasmic dynein is involved in nuclear migration in Aspergillus nidulans. AUTHOR(S) Xiang-X; Beckwith-SM; Morris-NR ADDRESS OF AUTHOR University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Department of Pharmacology, Piscataway 08854-5635. SOURCE (BIBLIOGRAPHIC CITATION) Proc-Natl-Acad-Sci-U-S-A. 1994 Mar 15; 91(6): 2100-4 INTERNATIONAL STANDARD SERIAL NUMBER 0027-8424 PUBLICATION YEAR 1994 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION UNITED-STATES ABSTRACT Nuclear migration plays an important role in the growth and development of many organisms including the multinuclear fungus Aspergillus nidulans. We have identified four genes, nudA, nudC, nudF, and nudG, in which temperature-sensitive mutations affect nuclear distribution. In this report, we describe the cloning of the nudA gene by complementation of the mutant phenotype by using a chromosome VIII-specific cosmid library. A genomic fragment of nudA hybridized to an mRNA of approximately 14 kb. Sequencing analysis of nudA revealed four ATP-binding sites that are characteristic of the cytoplasmic dynein heavy chain. The amino acid sequence of the nudA gene product shows 52% overall identity with the rat brain cytoplasmic dynein heavy chain. Our study provides in vivo evidence that dynein, a microtubule motor molecule, plays a role in the nuclear migration process. MINOR MESH HEADINGS Adenosine-Triphosphate-metabolism; Amino-Acid-Sequence; Aspergillus-nidulans-genetics; Cloning,-Molecular; Dynein-ATPase-metabolism; Genes,-Fungal; Genetic-Complementation-Test; Molecular-Sequence-Data; Mutation-; Phenotype-; Restriction-Mapping; Sequence-Homology,-Amino-Acid; Temperature- MAJOR MeSH HEADINGS *Aspergillus-nidulans-growth-and-development; *Cell-Nucleus-metabolism; *Cytoplasm-metabolism; *Dynein-ATPase-genetics CHECKTAGS Animal; Support,-U.S.-Gov't,-P.H.S. GENE SYMBOL nudA; nudC; nudF; nudG PUBLICATION TYPE JOURNAL-ARTICLE CAS REGISTRY NUMBER OR EC NUMBER EC 3.6.1.33; 56-65-5 NAME OF SUBSTANCE Dynein-ATPase; Adenosine-Triphosphate MEDLINE ACCESSION NUMBER 94181539 UPDATE CODE 9406 SECONDARY SOURCE IDENTIFIER GENBANK/U03904 ---------------------------------------------------------------------------- Record 4 of 16 in MEDLINE EXPRESS (R) 1991-1995 TITLE Binding selectivity of rhizoxin, phomopsin A, vinblastine, and ansamitocin P-3 to fungal tubulins: differential interactions of these antimitotic agents with brain and fungal tubulins [published erratum appears in Biochem Biophys Res Commun 1993 Feb 15;190(3):1180] AUTHOR(S) Li-Y; Kobayashi-H; Hashimoto-Y; Iwasaki-S ADDRESS OF AUTHOR Institute of Applied Microbiology, University of Tokyo, Japan. SOURCE (BIBLIOGRAPHIC CITATION) Biochem-Biophys-Res-Commun. 1992 Sep 16; 187(2): 722-9 Library Holdings Message Press to receive the full text via fax. Call Number Price: $26.75 plus fax surcharge INTERNATIONAL STANDARD SERIAL NUMBER 0006-291X PUBLICATION YEAR 1992 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION UNITED-STATES ABSTRACT The binding of four potent antimitotic agents, rhizoxin (RZX), phomopsin A (PMS-A), ansamitocin P-3 (ASMP-3), and vinblastine (VLB), to tubulins from RZX-sensitive and -resistant strains of Aspergillus nidulans, Schizosaccharomyces pombe, and Saccharomyces cerevisiae was investigated. Mycelial extracts to which RZX could bind contained beta-tubulin with Asn as the 100th amino acid residue (Asn-100) in all cases, and those without affinity for RZX contained beta-tubulins with either Ile-100 or Val-100. Though PMS-A shares the same binding site as RZX and ASMP-3 on porcine brain tubulin (Asn-100), only ASMP-3 bound Asn-100 fungal tubulins in a competitive manner with respect to RZX. PMS-A and VLB, which strongly bind to porcine brain tubulin, did not bind to any of the fungal mycelial extracts examined. The results indicate differential interactions of these antimitotic agents with brain and fungal tubulins. MINOR MESH HEADINGS Aspergillus-nidulans-metabolism; Binding-Sites; Binding,-Competitive; Brain-metabolism; Brain-Chemistry; Fungi-chemistry; Lactones-metabolism; Maytansine-analogs-and-derivatives; Maytansine-metabolism; Mycotoxins-metabolism; Saccharomyces-cerevisiae-metabolism; Schizosaccharomyces-metabolism; Swine-; Vinblastine-metabolism MAJOR MeSH HEADINGS *Antineoplastic-Agents-metabolism; *Fungi-metabolism; *Tubulin-metabolism CHECKTAGS Animal; Comparative-Study PUBLICATION TYPE JOURNAL-ARTICLE CAS REGISTRY NUMBER OR EC NUMBER 0; 0; 0; 0; 35846-53-8; 64925-80-0; 69279-90-9; 865-21-4; 90996-54-6 NAME OF SUBSTANCE Antineoplastic-Agents; Lactones; Mycotoxins; Tubulin; Maytansine; phomopsin; ansamitocins; Vinblastine; rhizoxin MEDLINE ACCESSION NUMBER 92412113 UPDATE CODE 9212 ---------------------------------------------------------------------------- Record 5 of 16 in MEDLINE EXPRESS (R) 1991-1995 TITLE Protein structure of pig liver 4-aminobutyrate aminotransferase and comparison with a cDNA-deduced sequence. AUTHOR(S) De-Biase-D; Maras-B; Bossa-F; Barra-D; John-RA ADDRESS OF AUTHOR Dipartimento di Scienze Biochimiche A. Rossi Fanelli, Universita La Sapienza, Roma, Italy. SOURCE (BIBLIOGRAPHIC CITATION) Eur-J-Biochem. 1992 Sep 1; 208(2): 351-7 Library Holdings Message Press to receive the full text via fax. Call Number Price: $16.75 plus fax surcharge INTERNATIONAL STANDARD SERIAL NUMBER 0014-2956 PUBLICATION YEAR 1992 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION GERMANY ABSTRACT The amino acid sequence of pig liver 4-aminobutyrate aminotransferase has been determined by gas-phase sequencing of proteolytically derived peptide fragments. The sequence differs substantially from that predicted for the same enzyme on the basis of the sequence of cDNA derived from pig brain in recently published work [Kwon, O., Park, J. & Churchich, J. E. (1992) J. Biol. Chem. 267, 7215-7216]. Apart from a few minor differences, the two sequences are completely different in the segment of protein comprising the 36 residues at positions 107-142. Insertion of a cytosine between bases 402 and 403 in the cDNA sequence, together with deletion of the guanine at position 510, results in a DNA sequence which predicts exactly the amino acid sequence determined by peptide analysis in the present work. The mammalian enzyme has approximately 44% sequence identity with the same enzyme from two unicellular eukaryotes (Saccharomyces cerevisiae, Aspergillus nidulans) and 22% identity with that from Escherichia coli. MINOR MESH HEADINGS Amino-Acid-Sequence; Aminobutyrate-Aminotransferase-genetics; Base-Sequence; Chromatography,-High-Pressure-Liquid; Molecular-Sequence-Data; Peptide-Fragments-chemistry; Sequence-Homology,-Nucleic-Acid; Spectrometry,-Mass,-Fast-Atom-Bombardment; Swine-; Trypsin-metabolism MAJOR MeSH HEADINGS *Aminobutyrate-Aminotransferase-chemistry; *DNA-chemistry; *Liver-enzymology CHECKTAGS Animal; Comparative-Study; Support,-Non-U.S.-Gov't PUBLICATION TYPE JOURNAL-ARTICLE CAS REGISTRY NUMBER OR EC NUMBER EC 2.6.1.19; EC 3.4.21.4; 0; 9007-49-2 NAME OF SUBSTANCE Aminobutyrate-Aminotransferase; Trypsin; Peptide-Fragments; DNA MEDLINE ACCESSION NUMBER 92394130 UPDATE CODE 9212 SECONDARY SOURCE IDENTIFIER GENBANK/P80147 ---------------------------------------------------------------------------- Record 6 of 16 in MEDLINE EXPRESS (R) 1991-1995 TITLE Mutational analysis of calmodulin in Saccharomyces cerevisiae. AUTHOR(S) Davis-TN ADDRESS OF AUTHOR Department of Biochemistry, University of Washington, Seattle. SOURCE (BIBLIOGRAPHIC CITATION) Cell-Calcium. 1992 Jun-Jul; 13(6-7): 435-44 Library Holdings Message Press to receive the full text via fax. Call Number Price: $16.00 plus fax surcharge INTERNATIONAL STANDARD SERIAL NUMBER 0143-4160 PUBLICATION YEAR 1992 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION SCOTLAND ABSTRACT Calmodulin is well characterized as an intracellular Ca2+ receptor in nonproliferating tissues such as muscle and brain. Several observations indicate that calmodulin is also required for cellular growth and division. Deletion of the calmodulin gene is a lethal mutation in Saccharomyces cerevisiae, Schizosaccharomyces pombe and Aspergillus nidulans. Expression of calmodulin antisense RNA in mouse C127 cells causes a transient arrest at G1 and metaphase. Although these results indicate calmodulin plays a critical function during proliferation, they do not reveal the function. S. cerevisiae offers an excellent system for identifying calmodulin functions. Because calmodulin mutants can be readily constructed by gene replacement the consequences of mutations in calmodulin can be directly examined in vivo without interference from wild-type calmodulin. The available wealth of information concerning all aspects of the yeast life cycle provides a large framework for interpretation of new results. The recent dissection of cell cycle regulation is just the latest example of the important insights provided by analyzing basic cellular processes in yeast. Whether studies of calmodulin in yeast will reveal a universal function is unknown. One encouraging result is that yeast cells relying on vertebrate calmodulin as their only source of calmodulin survive and grow well, even if the amount of vertebrate calmodulin is equivalent to the normal steady state levels of yeast calmodulin. This review discusses the varied techniques we are using to identify the functions of calmodulin in yeast. As part of the analysis, we are defining the essential elements of calmodulin structure. MINOR MESH HEADINGS Calmodulin-genetics; Mutation- MAJOR MeSH HEADINGS *Calmodulin-physiology; *Fungal-Proteins-genetics; *Saccharomyces-cerevisiae-physiology PUBLICATION TYPE JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL CAS REGISTRY NUMBER OR EC NUMBER 0; 0 NAME OF SUBSTANCE Calmodulin; Fungal-Proteins MEDLINE ACCESSION NUMBER 92370658 UPDATE CODE 9211 ---------------------------------------------------------------------------- Record 7 of 16 in MEDLINE EXPRESS (R) 1991-1995 TITLE Cloning and sequence determination of a cDNA encoding Aspergillus nidulans calmodulin-dependent multifunctional protein kinase. AUTHOR(S) Kornstein-LB; Gaiso-ML; Hammell-RL; Bartelt-DC ADDRESS OF AUTHOR Department of Biological Sciences, St. John's University Jamaica, NY 11439. SOURCE (BIBLIOGRAPHIC CITATION) Gene. 1992 Apr 1; 113(1): 75-82 Library Holdings Message Press to receive the full text via fax. Call Number Price: $23.50 plus fax surcharge INTERNATIONAL STANDARD SERIAL NUMBER 0378-1119 PUBLICATION YEAR 1992 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION NETHERLANDS ABSTRACT A partial cDNA encoding Aspergillus nidulans calmodulin-dependent multifunctional protein kinase (ACMPK) was isolated from a lambda ZAP expression library by immunoselection using monospecific polyclonal antibodies to the enzyme. The sequence of both strands of the cDNA (CMKa) was determined. The deduced amino acid (aa) sequence contained all eleven consensus domains found in serine/threonine protein kinases [Hanks et al., Science 241 (1988) 42-52], as well as a putative calmodulin-binding domain. The cDNA contained an intron, lacked an in-frame start codon, and was not polyadenylated. A full-length copy of CMKa was subsequently isolated from a lambda gt10 library of A. nidulans cDNA using a restriction fragment of the first clone as a probe. It contained an in-frame start codon, an open reading frame (ORF) of 1242 bp and was polyadenylated. The ORF encoded a protein of 414 aa residues with an M(r) of 46,895 and an isoelectric point pI = 6.4. These values are in good agreement with that observed for the native enzyme [Bartelt et al., Proc. Natl. Acad. Sci. USA 85 (1988) 3279-3283]. When aligned to optimize homology, 29% of the predicted aa sequence of ACMPK is identical to that of the alpha-subunit of rat brain calmodulin-dependent protein kinase II. ACMPK shares 40 and 44% identity in aa sequence with YCMK1 and YCMK2, respectively, two Ca2+/calmodulin-dependent protein kinases recently cloned from Saccharomyces cerevisiae [Pausch et al., EMBO J. 10 (1991) 1511-1522]. Results of Southern analysis of restriction digests of genomic DNA indicate that ACMPK is encoded by a single-copy gene. MINOR MESH HEADINGS Amino-Acid-Sequence; Aspergillus-nidulans-enzymology; Base-Sequence; Cloning,-Molecular-methods; DNA,-Fungal-isolation-and-purification; Gene-Library; Immunoassay-; Introns-; Molecular-Sequence-Data; Oligodeoxyribonucleotides-; Phosphorylation-; Protein-Kinases-analysis; Restriction-Mapping; Sequence-Homology,-Nucleic-Acid MAJOR MeSH HEADINGS *Aspergillus-nidulans-genetics; *DNA,-Fungal-genetics; *Protein-Kinases-genetics CHECKTAGS Comparative-Study; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S. PUBLICATION TYPE JOURNAL-ARTICLE CONTRACT OR GRANT NUMBERS GM37288GMNIGMS CAS REGISTRY NUMBER OR EC NUMBER EC 2.7.1.-; EC 2.7.1.37; 0; 0 NAME OF SUBSTANCE calmodulin-dependent-multiprotein-kinase; Protein-Kinases; DNA,-Fungal; Oligodeoxyribonucleotides MEDLINE ACCESSION NUMBER 92225350 UPDATE CODE 9207 SECONDARY SOURCE IDENTIFIER GENBANK/M74120; GENBANK/X58742; GENBANK/X58743; GENBANK/M76682; GENBANK/X60732; GENBANK/X60733; GENBANK/M79307; GENBANK/M79308; GENBANK/M79309; GENBANK/M79310 ---------------------------------------------------------------------------- Record 8 of 16 in MEDLINE EXPRESS (R) 1990 TITLE A case of cerebral aspergillosis caused by Aspergillus nidulans. Clinical, pathologic and mycologic identifications. AUTHOR(S) Tong-QJ; Chai-WX; Wang-ZF; Kou-JF; Qi-ZT; Wang-DL ADDRESS OF AUTHOR Department of Neurology, Beijing Friendship Hospital. SOURCE (BIBLIOGRAPHIC CITATION) Chin-Med-J-Engl. 1990 Jun; 103(6): 518-22 Library Holdings Message Press to receive the full text via fax. Call Number Price: $23.50 plus fax surcharge INTERNATIONAL STANDARD SERIAL NUMBER 0366-6999 PUBLICATION YEAR 1990 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION CHINA ABSTRACT A case of cerebral aspergillosis is reported, the presenting symptom was numbness of right face, which worsened after one year. CT-scan showed two enhanced low-density patches in the anterior and basal parts of right temporal lobe. During operation, an abscess in the deep part of right temporal lobe was revealed. The patient gradually felt amaurosis and oculomotor palsy of right eye. About six months later, she died from intracranial hypertension. Biopsy, as well as autopsy findings suggested fungal infection, and was identified as Aspergillus nidulans, which has probably never been reported in the literature. MINOR MESH HEADINGS Aspergillus-nidulans-isolation-and-purification; Brain-Abscess-etiology; Brain-Abscess-microbiology; Middle-Age MAJOR MeSH HEADINGS *Aspergillosis-; *Aspergillus-nidulans; *Brain-Abscess-pathology CHECKTAGS Case-Report; Female; Human PUBLICATION TYPE JOURNAL-ARTICLE; REVIEW; REVIEW-OF-REPORTED-CASES MEDLINE ACCESSION NUMBER 91005486 UPDATE CODE 9101 ---------------------------------------------------------------------------- Record 9 of 16 in MEDLINE EXPRESS (R) 1990 TITLE Chloroacetaldehyde is a powerful inducer of mitotic aneuploidy in Aspergillus nidulans. AUTHOR(S) Crebelli-R; Conti-G; Conti-L; Carere-A ADDRESS OF AUTHOR Istituto Superiore di Sanita, Rome, Italy. SOURCE (BIBLIOGRAPHIC CITATION) Mutagenesis. 1990 Mar; 5(2): 165-8 Library Holdings Message Press to receive the full text via fax. Call Number Price: $13.50 plus fax surcharge INTERNATIONAL STANDARD SERIAL NUMBER 0267-8357 PUBLICATION YEAR 1990 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION ENGLAND ABSTRACT The vinyl chloride metabolite chloroacetaldehyde (CAA) was tested for the induction of mitotic chromosome malsegregation in Aspergillus nidulans. Exposure of germinating conidia to CAA (16-64 microM) produced high rates of abnormal colonies with segregation of the whole first chromosome in the diploid strain P1, and abnormal, putative hyperploids in the haploid strain 35, indicating that CAA primarily induces abnormal chromosome segregation. Comparative assays with the known spindle poison chloral hydrate (CH), active in the dose range 6-10 mM, highlighted the unusual effectiveness of CAA in aneuploidy induction (the lowest effective concentration was 16 microM). Experiments on brain tubulin polymerization revealed an inhibitory effect by CAA only at concentrations 100-fold higher than those active in the induction of chromosome misdistribution in A. nidulans, possibly suggesting the involvement of alternative targets in its mechanism of action. MINOR MESH HEADINGS Acetaldehyde-toxicity; Aspergillus-nidulans-genetics; Cattle-; Crossing-Over-Genetics-drug-effects; Microtubules-drug-effects MAJOR MeSH HEADINGS *Acetaldehyde-analogs-and-derivatives; *Aneuploidy-; *Aspergillus-nidulans-drug-effects; *Chromosomes,-Fungal-drug-effects; *Mutagens- CHECKTAGS Animal; In-Vitro; Support,-Non-U.S.-Gov't PUBLICATION TYPE JOURNAL-ARTICLE CAS REGISTRY NUMBER OR EC NUMBER 0; 107-20-0; 75-07-0 NAME OF SUBSTANCE Mutagens; chloroacetaldehyde; Acetaldehyde MEDLINE ACCESSION NUMBER 90258753 UPDATE CODE 9008 ---------------------------------------------------------------------------- Record 10 of 16 in MEDLINE EXPRESS (R) 1983-1989 TITLE Rhizoxin resistant mutants with an altered beta-tubulin gene in Aspergillus nidulans. AUTHOR(S) Takahashi-M; Kobayashi-H; Iwasaki-S ADDRESS OF AUTHOR Institute of Applied Microbiology, University of Tokyo, Japan. SOURCE (BIBLIOGRAPHIC CITATION) Mol-Gen-Genet. 1989 Dec; 220(1): 53-9 Library Holdings Message Press to receive the full text via fax. Call Number Price: $16.50 plus fax surcharge INTERNATIONAL STANDARD SERIAL NUMBER 0026-8925 PUBLICATION YEAR 1989 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION GERMANY,-WEST ABSTRACT Rhizoxin and ansamitocin P-3 (a maytansinoid compound), potent inhibitors of mammalian brain tubulin assembly, inhibit growth of a variety of fungi including Aspergillus nidulans. Mutants of A. nidulans, benA10 which is a benomyl resistant beta-tubulin gene mutant and tubA1 which is a benomyl supersensitive alpha-tubulin gene mutant, were both sensitive to rhizoxin and ansamitocin P-3 to the same extent as wild-type strains. We isolated 18 rhizoxin resistant mutants of A. nidulans. All of these mutants were cross-resistant to ansamitocin P-3, but not to benzimidazole antimitotic drugs. These mutants mapped to two loci, rhiA and rhiB, and all of those with high resistance mapped to rhiA. The fact that the protein extracts of rhiA mutants lost rhizoxin binding affinity and that rhiA was closely linked to benA, the major beta-tubulin gene in A. nidulans, indicated that rhiA must be a structural gene for beta-tubulin and that rhiA mutants are a new class of beta-tubulin gene mutants. All of this suggested that, in A. nidulans, these antimitotic drugs bind to beta-tubulin, and that rhizoxin and ansamitocin P-3 share the same binding site but the site does not overlap with the benzimidazole binding site. Protein extracts from a rhiB mutant retained rhizoxin binding affinity, therefore this rhizoxin resistance mechanism should not be a tubulin mediated process. MINOR MESH HEADINGS Aspergillus-nidulans-drug-effects; Aspergillus-nidulans-growth-and-development; Benomyl-administration-and-dosage; Benomyl-pharmacology; Benzimidazoles-administration-and-dosage; Benzimidazoles-pharmacology; Cell-Division-drug-effects; Dose-Response-Relationship,-Drug; Drug-Resistance,-Microbial-genetics; Lactones-administration-and-dosage; Lactones-pharmacology; Lactones-pharmacokinetics MAJOR MeSH HEADINGS *Antibiotics,-Antifungal-pharmacology; *Aspergillus-nidulans-genetics; *Genes,-Fungal; *Mutation-; *Tubulin-genetics CHECKTAGS Support,-Non-U.S.-Gov't PUBLICATION TYPE JOURNAL-ARTICLE CAS REGISTRY NUMBER OR EC NUMBER 0; 0; 0; 0; 17804-35-2; 51-17-2; 90996-54-6 NAME OF SUBSTANCE Antibiotics,-Antifungal; Benzimidazoles; Lactones; Tubulin; Benomyl; benzimidazole; rhizoxin MEDLINE ACCESSION NUMBER 90114108 UPDATE CODE 9004 ---------------------------------------------------------------------------- ---------------------------------------------------------------------------- ---------------------------------------------------------------------------- Return to [Helix] [Image] ---------------------------------------------------------------------------- Register for PHP | Free Preview of PHP | What is Physicians' Home Page? | Membership Information and Rates | Special Offer for Residents | Special Offer for Physicians' SilverPlatter CD-ROM Customers Copyright 1996, SilverPlatter Education, Inc. WebSPIRS Version 3.0.24 --------------342B670CC3D Content-Type: text/plain; charset=us-ascii; name="glaxo6.bat" Content-Transfer-Encoding: 7bit Content-Disposition: inline; filename="glaxo6.bat" Terms of About Physicians' Home Register for Back to Use Page PHP Preview PHP Helix [Helix] [sp.nex[sp.nex[sp.nex[sp.ne[sp.nextform=help/c_srch.htm i] Show records Copyright Information ---------------------------------------------------------------------------- Record 11 of 16 in MEDLINE EXPRESS (R) 1983-1989 TITLE Calmodulin-dependent multifunctional protein kinase in Aspergillus nidulans. AUTHOR(S) Bartelt-DC; Fidel-S; Farber-LH; Wolff-DJ; Hammell-RL ADDRESS OF AUTHOR Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854. SOURCE (BIBLIOGRAPHIC CITATION) Proc-Natl-Acad-Sci-U-S-A. 1988 May; 85(10): 3279-83 INTERNATIONAL STANDARD SERIAL NUMBER 0027-8424 PUBLICATION YEAR 1988 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION UNITED-STATES ABSTRACT A Ca2+/calmodulin (CaM)-dependent multifunctional protein kinase has been isolated from Aspergillus nidulans and purified to homogeneity. Unlike any CaM-dependent multifunctional protein kinase described previously, the native enzyme from Aspergillus behaves as a monomer. The calculated molecular weight is 41,200. NaDodSO4/PAGE reveals a single protein band with an apparent Mr of 51,000. Two-dimensional isoelectric focusing/NaDodSO4/PAGE of the purified enzyme showed one major and one minor more acidic Coomassie blue-stained spot, both of which bind 125I-labeled calmodulin in a calcium-dependent manner. The kinase is autophosphorylated in a calcium- and CaM-dependent manner, yielding an increase in the amount and number of more acidic forms of the enzyme. The Aspergillus kinase catalyzes the Ca2+/CaM-dependent phosphorylation of known substrates of type II Ca2+/CaM-dependent protein kinases, including glycogen synthase, microtubule-associated protein 2, synapsin, tubulin, gizzard myosin light chain, and casein. Cross-reactivity between antiserum raised against native rat brain protein kinase II and 125I-labeled Aspergillus kinase has been detected. Two forms of CaM have been isolated from Aspergillus nidulans, both of which activate the Aspergillus kinase at lower concentrations than that required for activation by bovine brain CaM. MINOR MESH HEADINGS Brain-enzymology; Kinetics-; Molecular-Weight; Protein-Kinases-isolation-and-purification; Rats-; Substrate-Specificity MAJOR MeSH HEADINGS *Aspergillus-niger-enzymology; *Protein-Kinases-metabolism CHECKTAGS Animal; Comparative-Study; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S. PUBLICATION TYPE JOURNAL-ARTICLE CONTRACT OR GRANT NUMBERS GM37288; NS11252; GM34711 CAS REGISTRY NUMBER OR EC NUMBER EC 2.7.1.37; EC 2.7.10.- NAME OF SUBSTANCE Protein-Kinases; Calmodulin-Dependent-Protein-Kinases MEDLINE ACCESSION NUMBER 88217884 UPDATE CODE 8808 ---------------------------------------------------------------------------- Record 12 of 16 in MEDLINE EXPRESS (R) 1983-1989 TITLE An evaluation of the mutagenic, carcinogenic and teratogenic potential of microwaves. AUTHOR(S) Leonard-A; Berteaud-AJ; Bruyere-A SOURCE (BIBLIOGRAPHIC CITATION) Mutat-Res. 1983 Sep; 123(1): 31-46 Library Holdings Message Press to receive the full text via fax. Call Number Price: $23.50 plus fax surcharge INTERNATIONAL STANDARD SERIAL NUMBER 0027-5107 PUBLICATION YEAR 1983 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION NETHERLANDS ABSTRACT A notable proportion of the population is exposed to an increasing number of devices emitting microwaves, a form of non-ionizing electromagnetic radiation in the range 300-30000 mHz. The activation energy of microwave radiations is too small to directly modify any chemical bonds in the irradiated matter. At microwave frequencies the macroscopic dielectric properties of tissues are strongly determined by their water content. Tissues like muscle, brain, skin, with a high water content, have higher permittivity and conductivity values than bone or fat with low water contents. Owing to the energy transfer, to living tissues, by a dipolar relaxation mechanism of water molecules, the penetration of microwaves is limited and one observes a fast and very efficient heat-loss production. A review of the available literature shows that most results on the mutagenicity of microwaves are negative or can often be explained by a temperature enhancement. If microwaves are apparently unable to damage DNA at sub-thermal exposure levels, some results indicate, however, that they might easily potentiate the damaging action of other DNA antagonist agents such as UV or chemicals. MINOR MESH HEADINGS Aspergillus-nidulans-genetics; Cells,-Cultured; Chromosome-Aberrations; Drosophila-melanogaster-genetics; Lymphocytes-physiology; Lymphocytes-radiation-effects; Plants-genetics; Saccharomyces-cerevisiae-genetics; Species-Specificity MAJOR MeSH HEADINGS *Abnormalities-etiology; *Microwaves-adverse-effects; *Mutation-; *Neoplasms-etiology CHECKTAGS Animal; Human; Support,-Non-U.S.-Gov't PUBLICATION TYPE JOURNAL-ARTICLE MEDLINE ACCESSION NUMBER 83297468 UPDATE CODE 8312 ---------------------------------------------------------------------------- Record 13 of 16 in MEDLINE EXPRESS (R) 1966-1982 TITLE Enhancement of tissue invasion in murine aspergillosis by systemic administration of suspensions of killed Corynebacterium parvum. AUTHOR(S) Purnell-DM SOURCE (BIBLIOGRAPHIC CITATION) Am-J-Pathol. 1976 Jun; 83(3): 547-55 Library Holdings Message 0002-9440 11 The American Journal of Pathology web site: http://www.at-home.com/PATHOLOGY/ INTERNATIONAL STANDARD SERIAL NUMBER 0002-9440 PUBLICATION YEAR 1976 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION UNITED-STATES ABSTRACT The effect of killed Corynebacterium parvum vaccine on the course of murine aspergillosis is described. A grid-counting technique was employed to quantitate tissue invasion by Aspergillus nidulans in the brain, heart, and kidneys (the target organs) of normal mice and of mice treated systemically with killed C. parvum vaccine. Simultaneous treatment of mice with C. parvum and A. nidulans significantly increased the mortality rate, in contrast to treatment of mice with C. parvum prior to or following A. nidulans, which had no significant effect on mortality. Fungal invasion of the tissues of the brain and kidneys was significantly increased in mice pretreated or posttreated with C. parvum, but fungal invasion of the heart was not effected by these treatements. Simultaneous treatment of mice with C. parvum and A. nidulans significantly increased fungal invasion of the heart but did not effect tissue invasion of the brain and kidneys. It was concluded that killed C. parvum vaccine reduces host resistance to Aspergillus infection and facilitates the curse of fatal murine aspergillosis. These results suggest further caution in applying systemic C. parvum in the therapy of human neoplasia. MINOR MESH HEADINGS Aspergillosis-microbiology; Aspergillosis-therapy; Aspergillus-nidulans; Bacterial-Vaccines-therapeutic-use; Mice-; Mice,-Inbred-DBA MAJOR MeSH HEADINGS *Aspergillosis-pathology; *Disease-Models,-Animal; *Propionibacterium-acnes CHECKTAGS Animal; Male PUBLICATION TYPE JOURNAL-ARTICLE MEDLINE ACCESSION NUMBER 76229156 UPDATE CODE 7610 SUBSET AIM ---------------------------------------------------------------------------- Record 14 of 16 in MEDLINE EXPRESS (R) 1966-1982 TITLE Tubulin-like protein from Aspergillus nidulans. AUTHOR(S) Sheir-Neiss-G; Nardi-RV; Gealt-MA; Morris-NR SOURCE (BIBLIOGRAPHIC CITATION) Biochem-Biophys-Res-Commun. 1976 Mar 22; 69(2): 285-90 Library Holdings Message Press to receive the full text via fax. Call Number Price: $26.75 plus fax surcharge INTERNATIONAL STANDARD SERIAL NUMBER 0006-291X PUBLICATION YEAR 1976 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION UNITED-STATES MINOR MESH HEADINGS Brain-Chemistry; Chickens-; Electrophoresis,-Polyacrylamide-Gel; Species-Specificity; Swine- MAJOR MeSH HEADINGS *Aspergillus-nidulans-metabolism; *Glycoproteins-isolation-and-purification; *Tubulin-isolation-and-purification CHECKTAGS Animal; Comparative-Study; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S. PUBLICATION TYPE JOURNAL-ARTICLE MEDLINE ACCESSION NUMBER 76184115 UPDATE CODE 7608 ---------------------------------------------------------------------------- Record 15 of 16 in MEDLINE EXPRESS (R) 1966-1982 TITLE Quantitative tissue invasion of the murine brain as a phenotypic marker of strain virulence in Aspergillus nidulans. AUTHOR(S) Purnell-DM SOURCE (BIBLIOGRAPHIC CITATION) Sabouraudia. 1975 Jul; 13(2): 209-16 INTERNATIONAL STANDARD SERIAL NUMBER 0036-2174 PUBLICATION YEAR 1975 LANGUAGE OF ARTICLE ENGLISH COUNTRY OF PUBLICATION SCOTLAND ABSTRACT In this study the extent of fungal invasion in tissues of the target organs (brain, heart and kidney) has been quantitated histologically in DBA/2J mice inoculated intravenously with 3 strains of Aspergillus nidulans of different virulence. This was done to determine the relation between tissue invasion and strain virulence as determined by time-mortality bioassay. It was found that quantitatively tissue invasion by A. nidulans was target organ specific. Relative tissue invasion within each of the tissues examined was dependent on the strain of A. nidulans injected. In the brain a direct relationship between strain virulence and the extent of tissue invasion was found. This relationship was not observed in the other 2 target organs. The observations suggest that an important phenotypic marker of murine virulence in A. nidulans is the relative ability to invade the tissues of the murine brain. MINOR MESH HEADINGS Aspergillosis-mortality; Heart-microbiology; Kidney-microbiology; Mice-; Mice,-Inbred-Strains; Phenotype-; Virulence- MAJOR MeSH HEADINGS *Aspergillosis-microbiology; *Aspergillus-nidulans-pathogenicity; *Brain-microbiology CHECKTAGS Animal; Male PUBLICATION TYPE JOURNAL-ARTICLE MEDLINE ACCESSION NUMBER 76013697 UPDATE CODE 7601 ---------------------------------------------------------------------------- Record 16 of 16 in MEDLINE EXPRESS (R) 1966-1982 TITLE The histopath