Progeria

[CHS Library Remote, medline]

1
UI  - 95166272
AU  - Sugita K
AU  - Suzuki N
AU  - Fujii K
AU  - Niimi H
IN  - Department of Pediatrics, Faculty of Medicine, University of Chiba,
      Japan.
TI  - Reduction of unscheduled DNA synthesis and plasminogen activator
      activity in Hutchinson-Gilford fibroblasts during passaging in
      vitro: partial correction by interferon-beta.
SO  - Mutation Research 1995 Feb;316(3):133-8
AB  - Two fibroblast cell lines (PG3KT and PG1NA) derived from
      Hutchinson-Gilford syndrome (progeria) cases were characterized, at
      various population doubling levels (PDL), with respect to the
      capacity of ultraviolet light (UV, mainly 254 nm wavelength)-induced
      unscheduled DNA synthesis (UDS) and plasminogen activator-like
      protease activity (PA). The UDS levels in PG3KT and PG1NA cells at
      PDL 2-3 were only slightly less than those in normal fibroblasts.
      With increasing PDL, both progeria cell lines exhibited reduction of
      the UDS levels and undetectable ones at PDL 9-11. Prompt and
      transient induction of PA was also detectable at less than PDL 5,
      whereas it was undectable at higher PDL. However, the levels of UDS
      and PA induction were increased about 3-7 times after pretreatment
      with 100 IU/ml human interferon (HuIFN)-beta preparations for more
      than 24 h prior to UV irradiation, although UDS and PA were
      undetectable at more than PDL 10. These results suggest that
      cytokines such as HuIFN-beta transiently compensate for the
      decreases in UDS and PA inducibility in progeria cells with aging.

2
UI  - 95123867
AU  - Rautenstrauch T
AU  - Snigula F
AU  - Wiedemann HR
IN  - Stadt. Krankenhaus Munchen-Harlaching, Klinik fur Kinder- und
      Jugendmedizin, Kiel.
TI  - [Neonatal progeroid syndrome (Wiedemann-Rautenstrauch). A follow-up
      study]. [Review] [German]
SO  - Klinische Padiatrie 1994 Nov-Dec;206(6):440-3
AB  - The diagnostic criteria of the neonatal progeroid syndrome (NPS)
      are: intrauterine and postnatal growth failure, hydrocephalic
      appearance, prominent scalp veins, old-looking face, absence of
      subcutaneous fat and neonatal teeth. Until now altogether nine cases
      have been reported, which were predominant diagnosed in infant age.
      The NPS is in general assigned to the autosomal recessive trait.
      With increasing age the outward appearance stays unchanged. The in
      1977 under diagnose progeria presented patient is now 16 years old.
      With her a considerable atactic movement disturbance developed next
      to a psychomotoric retardation. The change in metabolism of
      proteoglycane that was remarkable in infant age is now no longer
      provable. [References: 16]

3
UI  - 94338463
AU  - Matsuo S
AU  - Takeuchi Y
AU  - Hayashi S
AU  - Kinugasa A
AU  - Sawada T
IN  - Department of Pediatrics, Children's Research Hospital, Kyoto,
      Japan.
TI  - Patient with unusual Hutchinson-Gilford syndrome (progeria).
SO  - Pediatric Neurology 1994 May;10(3):237-40
AB  - A patient with unusual Hutchinson-Gilford syndrome (progeria) is
      reported. This 7-year-old boy had all the characteristics of
      progeria, except for coxa valga and the "horse-riding" stance. A
      previous cerebral infarction was detected in the right putamen on
      cranial magnetic resonance imaging. During treadmill exercise test
      electrocardiography, ST depression suggested the existence of
      arteriosclerotic lesions. Skin fibroblast culture exhibited 76%
      DNA-repair capacity compared to normal. He has not manifested
      endocrinologic abnormalities. From these findings it is concluded
      that this patient has an incomplete case of Hutchinson-Gilford
      syndrome and that a correlation may exist between the clinical
      features and the degree of DNA-repair capacity.

4
UI  - 94250975
AU  - Erdem N
AU  - Gunes AT
AU  - Avci O
AU  - Osma E
IN  - Department of Pediatrics, Faculty of Medicine, Dokuz Eylul
      University, Izmir, Turkey.
TI  - A case of Hutchinson-Gilford progeria syndrome mimicking scleredema
      in early infancy.
SO  - Dermatology 1994;188(4):318-21
AB  - We report a case of Hutchinson-Gilford progeria syndrome (HGPS). The
      patient showed the characteristics of scleredema at the age of 2.5
      months but developed all the manifestations of HGPS gradually until
      10 months old. The possibility of development of HGPS should by
      considered in any case of scleredema at birth or in early infancy.

5
UI  - 94234810
AU  - Carrel T
AU  - Pasic M
AU  - Tkebuchava T
AU  - Turina J
AU  - Jenni R
AU  - Turina MI
IN  - Clinic for Cardiovascular Surgery, University Hospital, Zurich,
      Switzerland.
TI  - Aortic homograft and mitral valve repair in a patient with Werner's
      syndrome.
SO  - Annals of Thoracic Surgery 1994 May;57(5):1319-20
AB  - We report the case of a 66-year-old man suffering from Werner's
      syndrome (adult progeria); he presented with several cardiac
      disorders, including coronary artery disease, aortic stenosis, and
      mitral regurgitation, mainly due to calcific deposits in the mitral
      annulus and the aortic cusps. Treatment consisted of mitral repair,
      homograft replacement of the aortic valve, and coronary artery
      bypass grafting. Avoidance of prosthetic material because of chronic
      infectious skin ulcers constituted the main goal of the operation.

6
UI  - 93357773
AU  - Warnecke P
AU  - Weiss AS
IN  - Department of Biochemistry, University of Sydney, NSW, Australia.
TI  - A ScaI RFLP at the E-selectin (SELE) locus in a progeria family.
SO  - Human Molecular Genetics 1993 Jun;2(6):825

7
UI  - 94174845
AU  - Ha JW
AU  - Shim WH
AU  - Chung NS
IN  - Cardiology Division Yonsei Cardiovascular Center, Yonsei University
      College of Medicine, Seoul Korea.
TI  - Cardiovascular findings of Hutchinson-Gilford syndrome--a Doppler
      and two-dimensional echocardiographic study.
SO  - Yonsei Medical Journal 1993 Dec;34(4):352-5
AB  - Progeria, also known as Hutchinson-Gilford syndrome, is an extremely
      rare condition originally described by Hutchinson in 1886. Death
      results from cardiac complications in the majority of cases and
      usually occurs at an average age of fourteen years. We recently
      experienced a patient with progeria who died suddenly after
      symptomatic improvement with conservative treatment. A Doppler and
      two-dimensional echocardiographic study revealed an enlarged and
      hypertrophied left ventricle with reduced global systolic function
      and senile aortic calcific stenosis (peak systolic pressure
      gradient: 50 mmHg) with a moderate degree of aortic regurgitation.
      Doppler findings of restrictive hemodynamic suggest severe left
      ventricular dysfunction due to multiple influences from the aging
      process, coronary artery and valvular heart disease.

8
UI  - 94066589
AU  - Giro M
AU  - Davidson JM
IN  - Department of Pathology, Vanderbilt University School of Medicine,
      Nashville, TN 37232-2561.
TI  - Familial co-segregation of the elastin phenotype in skin fibroblasts
      from Hutchinson-Gilford progeria.
SO  - Mechanisms of Ageing & Development 1993 Aug 15;70(3):163-36
AB  - Elastin and type IV collagen production are markedly elevated in
      fibroblasts derived from the skin of patients with
      Hutchinson-Gilford progeria (HGP). Fibroblasts from three affected
      children and their parents were compared to normal human skin
      fibroblasts with respect to elastin production as a function of
      different concentrations of calf serum and the cytokines,
      transforming growth factor-beta and basic fibroblast growth factor
      (TGF-beta 1, bFGF). In cultured fibroblasts from the parents of
      probands that were very high elastin producers (> 10(5) molecular
      equivalents/cell per h), at least one parent (mother) presented the
      same phenotype. Overproduction of elastin in culture could have been
      due to increased sensitivity of HGP strains to stimuli present in
      serum; however, relative stimulation of elastin production by calf
      serum in cell strains from HGP elastin over-producers was less than
      half the control strain. In most of the cultures examined, the
      responsiveness of elastin production to TGF-beta 1 was almost absent
      when compared to the response of normal fibroblasts. HGP strains
      with high elastin production modified conditioned medium to enhance
      elastin production in normal cells. These results suggest the
      presence, in HGP skin fibroblasts, of inheritance of high elastin
      production that is associated with accelerated aging.

9
UI  - 93229793
AU  - Hall JW 3d
AU  - Denneny JC 3d
IN  - Division of Hearing and Speech Sciences, School of Medicine,
      Vanderbilt University, Nashville, Tennessee.
TI  - Audiologic and otolaryngologic findings in progeria: case report.
SO  - Journal of the American Academy of Audiology 1993 Mar;4(2):116-21
AB  - Progeria is a rare syndrome, with an estimated incidence of 1 per
      250,000 births. Although children with progeria have the appearance
      of premature aging or senility, the term is misleading because
      reported cases of progeria have not manifested most physical or
      biochemical aspects of old age. Many children with progeria appear
      normal at birth and then progressively, and rather rapidly, develop
      the characteristic features during early childhood. Although first
      described in the 1880s, only approximately 100 cases of progeria are
      reported in the international literature. The single case study of
      hearing in progeria, which appeared in 1965, is limited to pure-tone
      and speech audiometry findings. We report the results of
      otolaryngologic examination and pure-tone, speech, immittance, and
      auditory brainstem response (ABR) audiometry for a 5-year-old female
      with progeria. The patient had a mild-to-moderate, bilateral,
      conductive hearing loss. Immittance measurements were consistent
      with fixation of the ossicular chain and this was confirmed
      surgically. Mildly prolonged ABR wave I-V latencies suggest possible
      auditory central nervous system involvement.

10
UI  - 93211388
AU  - Clark MA
AU  - Weiss AS
IN  - Department of Biochemistry, University of Sydney, N.S.W. Australia.
TI  - Elevated levels of glycoprotein gp200 in progeria fibroblasts.
SO  - Molecular & Cellular Biochemistry 1993 Mar 10;120(1):51-60
AB  - The glycosylation of proteins in fibroblasts from people with the
      premature ageing disease Hutchinson-Gilford Progeria Syndrome
      (progeria) was investigated. Protein was prepared from fibroblast
      cell lines established from skin biopsy taken from progeria patients
      and control donors. Glycoproteins were labelled by the covalent
      attachment of the steroid hapten digoxygenin to the sugar group.
      After separation of total protein by SDS-PAGE and electroblotting
      onto Immobilon-PTM, glycoproteins were detected by enzyme
      immunoassay. We have observed a glycoprotein of M(r) 200 kDa which
      is consistently present in protein preparations from progeria
      fibroblasts and which is absent, or markedly reduced, in
      preparations from control fibroblasts. This suggests that it may be
      useful as a marker for progeria. Similar analysis of progeria
      lymphoblast and control lymphoblast cultures did not show this
      altered pattern of glycosylated proteins, indicating that it may be
      cell-type specific. Glycoproteins were also detected by labelling
      fibroblasts in vitro with D-[6-3H]glucosamine hydrochloride followed
      by SDS-PAGE of isolated protein and subsequent fluorography.
      Profiles of glycoproteins from progeria and control fibroblasts were
      consistent with those obtained from labelling of carbohydrate groups
      with digoxygenin. Protease digestion of cell protein verified that
      the band at M(r) 200 kDa contains a protein core. Characteristic
      features of progeria primarily involve the connective tissue and
      include wrinkled and loose skin, loss of soft tissue, thin limbs and
      stiff joints. Death of progeria patients is usually a result of
      cardiovascular abnormalities. The most consistent manifestations
      thus involve the connective tissue. The glycoprotein of M(r) 200 kDa
      which we have observed in progeria fibroblasts in vitro could
      reflect a perturbation in glycosylation which may underly the
      connective tissue defects seen in progeria.

11
UI  - 93206822
AU  - Smith AS
AU  - Wiznitzer M
AU  - Karaman BA
AU  - Horwitz SJ
AU  - Lanzieri CF
IN  - Department of Radiology, University Hospitals of Cleveland, OH
      44106.
TI  - MRA detection of vascular occlusion in a child with progeria.
SO  - Ajnr: American Journal of Neuroradiology 1993 Mar-Apr;14(2):441-3
AB  - We report a case of progeria and the utility of visualizing the
      cerebrovascular anatomy by using MR angiography. A 4-year-old child
      with Hutchinson-Guilford syndrome developed symptoms of ischemia and
      MR angiography showed bilateral occlusion of internal carotid and
      vertebral artery origins; the anterior spinal artery was prominent.

12
UI  - 92347470
AU  - Millis AJ
AU  - Hoyle M
AU  - McCue HM
AU  - Martini H
IN  - Department of Biological Sciences, State University of New York,
      Albany 12222.
TI  - Differential expression of metalloproteinase and tissue inhibitor of
      metalloproteinase genes in aged human fibroblasts.
SO  - Experimental Cell Research 1992 Aug;201(2):373-9
AB  - The basal levels of mRNAs encoding two metalloproteinases,
      collagenase and stromelysin, were increased as a function of in
      vitro serial subcultivation (cellular aging) of human fibroblasts.
      Procollagenase and prostromelysin synthesis and secretion were also
      greater in the old cultures (late passage). In contrast, the
      steady-state expression of mRNA for an inhibitor of
      metalloproteinases, tissue inhibitor of metalloproteinase-1
      (TIMP-1), in late-passage cultures was lower than that in young cell
      cultures (early passage). Each mRNA was analyzed using total RNA
      preparations isolated from normal fibroblast cultures at different
      phases of the in vitro life span and from cultures derived from
      donors with the premature senescence syndromes characterized as
      Werner syndrome, progeria (Hutchinson-Gilford) syndrome, or Cockayne
      syndrome. In normal cell cultures expression of metalloproteinase
      mRNAs was increased after the culture had completed greater than 90%
      of the in vitro life span, and the reduction in TIMP-1 mRNA
      expression occurred after the culture had completed greater than 74%
      of the in vitro lifespan. In Werner syndrome cultures expression of
      metalloproteinase and TIMP-1 mRNAs was similar to the level of
      expression observed in late-passage cell cultures. Levels of
      metalloproteinase and TIMP-1 mRNA expression in progeria and
      Cockayne syndromes were similar to those of early-passage cell
      cultures. To determine if young and old cells were each responsive
      to mediators of metalloproteinase synthesis, cultures were treated
      with phorbol ester or cytokines.
      12-O-tetradecanoylphorbol-13-acetate treatment increased the
      steady-state levels of all three mRNAs in young, old, and Werner
      syndrome cultures and increased procollagenase levels in all
      cultures. Early- and late-passage cell cultures also responded to
      cytokines. Interleukin-1 alpha treatment increased collagenase and
      stromelysin mRNA levels while transforming growth factor-beta
      reduced the steady-state levels of both transcripts. Neither
      cytokine affected the steady-state level of TIMP-1 mRNA. The results
      indicate that in vitro cellular aging is associated with changes in
      expression of mRNAs encoding proteins that mediate inflammatory
      responses and connective tissue remodeling.

13
UI  - 93194324
AU  - Ghosh S
TI  - Progeria [letter; comment].
SO  - Indian Pediatrics 1992 Nov;29(11):1445

14
UI  - 93141744
AU  - Mateos Romero L
AU  - Porta Aznares MN
IN  - Servicio de Medicina Interna, Hospital General Virgen de la Luz,
      Cuenca.
TI  - [Werner's syndrome. Report of a new case]. [Spanish]
SO  - Revista Clinica Espanola 1992 Nov;191(8):430-2
AB  - Werner syndrome or adult progeria is a very rare disease transmitted
      in a recessive autosomic way. It is characterized by a pathologic
      and premature aging in all organs and systems, which begins
      generally between 1st and 3rd decades of life. We discuss a new case
      with a very visible expression both clinical as well as analytical,
      highlighting the characteristic chromosomic study.

15
UI  - 93120046
AU  - Fernandez-Palazzi F
AU  - McLaren AT
AU  - Slowie DF
IN  - Head Service C of Orthopedics, Hospital San Juan de Dios, Caracas,
      Venezuela.
TI  - Report on a case of Hutchinson-Gilford progeria, with special
      reference to orthopedic problems.
SO  - European Journal of Pediatric Surgery 1992 Dec;2(6):378-82
AB  - Hutchinson-Gilford progeria is a very rare syndrome of premature
      aging and often features many orthopedic abnormalities. This is a
      case report on a young boy suffering from progeria. His orthopedic
      history included bilateral talus deformities of the feet, bilateral
      dislocated hips, pes planus, a fractured femur (which healed without
      complications), aseptic necrosis in the left nuclear head of the
      femur, bilateral fixed hip flexion deformities, bone dysplasia,
      osteoporosis and osteolysis.

16
UI  - 93119406
AU  - Wagle WA
AU  - Haller JS
AU  - Cousins JP
IN  - Department of Radiology, Albany Medical Center, NY 12208.
TI  - Cerebral infarction in progeria.
SO  - Pediatric Neurology 1992 Nov-Dec;8(6):476-7

17
UI  - 93066190
AU  - Allsopp RC
AU  - Vaziri H
AU  - Patterson C
AU  - Goldstein S
AU  - Younglai EV
AU  - Futcher AB
AU  - Greider CW
AU  - Harley CB
IN  - Department of Biochemistry, McMaster University, Hamilton, ON,
      Canada.
TI  - Telomere length predicts replicative capacity of human fibroblasts.
SO  - Proceedings of the National Academy of Sciences of the United States of
      America 1992 Nov 1;89(21):10114-8
AB  - When human fibroblasts from different donors are grown in vitro,
      only a small fraction of the variation in their finite replicative
      capacity is explained by the chronological age of the donor. Because
      we had previously shown that telomeres, the terminal guanine-rich
      sequences of chromosomes, shorten throughout the life-span of
      cultured cells, we wished to determine whether variation in initial
      telomere length would account for the unexplained variation in
      replicative capacity. Analysis of cells from 31 donors (aged 0-93
      yr) indicated relatively weak correlations between proliferative
      ability and donor age (m = -0.2 doubling per yr; r = -0.42; P =
      0.02) and between telomeric DNA and donor age (m = -15 base pairs
      per yr; r = -0.43; P = 0.02). However, there was a striking
      correlation, valid over the entire age range of the donors, between
      replicative capacity and initial telomere length (m = 10 doublings
      per kilobase pair; r = 0.76; P = 0.004), indicating that cell
      strains with shorter telomeres underwent significantly fewer
      doublings than those with longer telomeres. These observations
      suggest that telomere length is a biomarker of somatic cell aging in
      humans and are consistent with a causal role for telomere loss in
      this process. We also found that fibroblasts from Hutchinson-Gilford
      progeria donors had short telomeres, consistent with their reduced
      division potential in vitro. In contrast, telomeres from sperm DNA
      did not decrease with age of the donor, suggesting that a mechanism
      for maintaining telomere length, such as telomerase expression, may
      be active in germ-line tissue.

18
UI  - 92372368
AU  - Wollina U
AU  - Reuter A
AU  - Schaarschmidt H
AU  - Muller E
AU  - Maak B
AU  - Schmidt U
IN  - Klinik und Poliklinik fur Hautkrankheiten,
      Friedrich-Schiller-Universitat, Jena.
TI  - [Hutchinson-Gilford syndrome]. [German]
SO  - Hautarzt 1992 Jul;43(7):453-7
AB  - A case report on a 6-year-old boy suffering from the extremely rare
      Hutchinson-Gilford syndrome (progeria) is presented. The results of
      histopathological and immunohistological examination of the
      scar-like skin lesions are reported. Subcutaneous amorphous nodules
      were eosinophilic, PAS- und elastica-negative und remained unstained
      with antibodies against collagen type IV, vimentin, and collagenase.
      The dense perivascular infiltration consisted of CD4+, CD8-,
      alpha-1-antichymotrypsin-, MAC 387-, and some vimentin-positive
      cells. Perinodular blood vessels were more abundant and had a
      thickened wall. Collagen bundles were swollen. The epidermis
      appeared atrophic with focal basal cell degeneration.

19
UI  - 92324630
AU  - Sweeney KJ
AU  - Weiss AS
IN  - Department of Biochemistry, University of Sydney, NSW, Australia.
TI  - Hyaluronic acid in progeria and the aged phenotype?. [Review]
SO  - Gerontology 1992;38(3):139-52
AB  - Hyaluronic acid (HA) is implicated in functions such as vascularity,
      morphogenesis, repair, and the general integrity of the
      extracellular matrix. Hence, it is considered possible that HA is
      involved in the most conspicuous features of the progeroid
      phenotype. However, it is not known whether the increase in HA
      excretion seen in progeria patients is due to a primary genetic
      defect or is a secondary effect due to some deeper problem. The
      phenomenon of 'normal' aging is suggested to have a more complex
      etiology and phenotype than progeria and the role of HA levels is
      less well-defined. [References: 49]

20
UI  - 92272018
AU  - Brown WT
IN  - Department of Human Genetics, New York State Institute for Basic
      Research, Staten Island 10314.
TI  - Progeria: a human-disease model of accelerated aging. [Review]
SO  - American Journal of Clinical Nutrition 1992 Jun;55(6 Suppl):1222S-1224S
AB  - Progeria is a rare genetic disease with striking features that
      resemble accelerated aging. The inheritance pattern, paternal age
      effect, and lack of consanguinity argue that it is due to a sporadic
      dominant mutation. We have observed elevated levels of hyaluronic
      acid (HA) excretion in progeria patients. In several progeria
      patients we observed normal levels of growth hormone (GH) but very
      low levels of insulin-like growth factor I along with very high
      basal metabolic rates (BMRs). A trial of GH treatment was begun,
      which resulted in a marked increase in linear growth and a
      paradoxical drop in BMRs in these two patients. We hypothesize that
      the failure of patients with progeria to thrive may be due to a
      bioinactive form of GH and a lack of vasculogenesis caused by excess
      HA. An understanding of the progeria genetic mutation may define a
      key gene with a major effect on normal aging. [References: 29]

21
UI  - 91106466
AU  - Saito H
AU  - Moses RE
IN  - Department of Cell Biology, Baylor College of Medicine, Houston,
      Texas 77030.
TI  - Immortalization of Werner syndrome and progeria fibroblasts.
SO  - Experimental Cell Research 1991 Feb;192(2):373-9
AB  - Human fibroblast cells from two different progeroid syndromes,
      Werner syndrome (WS) and progeria, were established as immortalized
      cell lines by transfection with plasmid DNA containing the SV40
      early region. The lineage of each immortalized cell line was
      confirmed by VNTR analysis. Each of the immortalized cell lines
      maintained its original phenotype of slow growth. DNA repair ability
      of these cells was also studied by measuring sensitivity to killing
      by uv or the DNA-damaging drugs methyl methansulfonate, bleomycin,
      and cis-dichlorodiamine platinum. The results showed that both WS
      and progeria cells have normal sensitivity to these agents.

22
UI  - 91267288
AU  - Briata P
AU  - Bellini C
AU  - Vignolo M
AU  - Gherzi R
IN  - Laboratories of Immunobiology, National Cancer Institute, Genoa,
      Italy.
TI  - Insulin receptor gene expression is reduced in cells from a progeric
      patient.
SO  - Molecular & Cellular Endocrinology 1991 Jan;75(1):9-14
AB  - We have studied a 15-year-old girl (P1) suffering from the
      Hutchinson-Gilford syndrome (progeria) associated with a severe
      insulin resistance. Insulin binding activity to P1 erythrocytes was
      85% reduced when compared to that measured in ten normal controls
      matched for sex and age. This finding was confirmed in Epstein-Barr
      virus (EBV)-transformed lymphoblasts and depends on a reduction in
      insulin receptor number. Also the amount of total insulin receptors,
      [35S]methionine labeled and immunoprecipitated, was 90% reduced in
      P1 lymphoblasts when compared to controls. Next, we measured insulin
      receptor mRNA levels and we found undetectable levels of insulin
      receptor transcript in P1 EBV-transformed lymphoblasts, in the
      absence of any rearrangement of insulin receptor gene as evaluated
      by Southern blot analysis. The marked reduction in insulin receptor
      gene expression probably accounts for the severe insulin resistance
      presented by the patient. Despite extensive studies, the molecular
      basis of progeria is still unknown. The near complete absence of a
      molecule crucial in the transduction of cell growth and
      differentiation signals could be involved in the accelerated aging
      of the patient.

23
UI  - 91260017
AU  - Colige A
AU  - Roujeau JC
AU  - De la Rocque F
AU  - Nusgens B
AU  - Lapiere CM
IN  - Laboratory of Experimental Dermatology, Centre Hospitalier
      Universitaire Sart Tilman, University of Liege, Sart Tilman,
      Belgium.
TI  - Abnormal gene expression in skin fibroblasts from a
      Hutchinson-Gilford patient.
SO  - Laboratory Investigation 1991 Jun;64(6):799-806
AB  - We had the opportunity to investigate a new case of
      Hutchinson-Gilford progeria, a rare disease commonly regarded as a
      model in the study of aging. Two strains of fibroblasts (strains 1
      and 2) were derived from two pieces of a skin biopsy. These two
      populations multiplied as normal cells at low population doubling
      level but senesced rapidly and stopped proliferating after 14 or 15
      population doubling levels. Interestingly, an unusual pattern of
      growth in clusters was observed for strain 1. The level of collagen
      and noncollagen protein synthesis of both strains of affected
      fibroblasts was similar to that of normal fibroblasts as determined
      by [3H]proline incorporation measurement and was similarly affected
      by varying serum concentrations. The pattern of the main types of
      newly synthesized collagen polypeptides analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis was similar in normal and
      progeria cells. The steady-state level of mRNAs coding for
      macromolecules of the extracellular matrix did not provide any
      differences between affected and control fibroblasts except for a
      strong increase of elastin and of alpha 1 and alpha 2 type IV
      procollagen mRNA mainly in strain 1 and less marked in strain 2.
      Interestingly, senescent progeria fibroblasts exhibited a reduced
      level of all the tested mRNAs, whereas collagen type IV and elastin
      mRNAs remained elevated. As suggested by immunofluorescence and
      immunoblotting studies, the increased amount of type IV mRNAs was
      paralleled by an enhanced production of type IV collagen by
      fibroblasts in vitro. Histologic examination of the skin revealed a
      superabundant network of abnormal elastic fibers in the reticular
      dermis and a thickening of basement membranes. The relationship
      between these alterations and aging in progeria is discussed.

24
UI  - 92226184
AU  - Colige A
AU  - Nusgens B
AU  - Lapiere CM
IN  - Laboratory of Experimental Dermatology, Tour de Pathologie,
      University of Liege, Belgium.
TI  - Altered response of progeria fibroblasts to epidermal growth factor.
SO  - Journal of Cell Science 1991 Nov;100 ( Pt 3):649-55
AB  - The Hutchinson-Gilford syndrome (progeria) is a rare disorder in
      childhood characterized by premature and accelerated aging. This
      study reports the effect of a potent growth factor, EGF, on the
      proliferative capacities and extracellular matrix macromolecules and
      collagenase expression of two strains of progeria skin-derived
      cells. At low population doubling levels (PDL less than 10),
      confluent cultures of progeria fibroblasts made quiescent by
      lowering the concentration of serum in the medium did not respond to
      EGF while the mitotic activity of normal PDL-matched fibroblasts was
      almost maximally restored upon addition of EGF. No obvious
      difference between normal and low PDL progeria fibroblasts was
      observed in the number and in the affinity of the receptors measured
      by [125I]EGF binding. The synthesis of collagen and non-collagen
      proteins was similar in normal and affected cells at low and high
      serum concentration and both types of cells responded to EGF by a
      specific inhibition of collagen synthesis. Besides a normal level of
      mRNA coding for type I and type III collagens, collagenase and
      laminin, progeria fibroblasts expressed a high level of elastin and
      type IV collagen mRNA. Like normal fibroblasts, progeria cells
      responded to EGF by a decrease in the level of mRNA for fibrillar
      collagens and elastin. In contrast, a complete lack of response to
      EGF was observed for collagenase mRNA whereas the expression of this
      enzyme was strikingly induced by EGF in normal PDL-matched cells.
      The abnormal expression of type IV collagen was not significantly
      modified by EGF. At PDL greater than 10, progeria cells exhibited
      features of senescence. A significant reduction of collagen
      synthesis was observed and no further inhibition by EGF was
      recorded.

25
UI  - 92205957
AU  - Tkach VE
AU  - Chmut VG
AU  - Fishchuk VA
TI  - [A case of progeria]. [RUSSIAN]
SO  - Vrachebnoe Delo 1991 Oct;(10):119-21

26
UI  - 92166601
AU  - Lok C
AU  - Ruto F
AU  - Labeille B
AU  - Pietri J
AU  - Denoeux JP
IN  - Service de Dermatologie et Venereologie, Hopital Sud, C.H.R.U.,
      Amiens.
TI  - [Leg ulcers in Werner's syndrome. Report of one case]. [French]
SO  - Journal des Maladies Vasculaires 1991;16(4):381-2
AB  - Werner's syndrome (adult progeria) is a rare autosomal recessive
      condition characterized mainly by a characteristic habitus (short
      stature, light body weight) scleroderma like changes of the limbs
      and premature aging. Chronic leg ulcers appears in about fifty per
      cent of the patients. These ulcers can be related to the combination
      of mechanical factors on atrophic subcutaneous tissue and skin of
      the feet and leg associated with early arteriosclerosis (20%) and
      diabetes mellitus (60%).

27
UI  - 92100114
AU  - Poot M
IN  - Department of Human Genetics, University of Wurzburg, Germany.
TI  - Oxidants and antioxidants in proliferative senescence. [Review]
SO  - Mutation Research 1991 Mar-Nov;256(2-6):177-89
AB  - In terms of the amount of experimental research it has generated the
      free radical theory of ageing is one of the most popular hypotheses
      to explain this ubiquitous phenomenon. From the theory two
      postulates were derived: either cellular defence mechanisms against
      free radical-dependent oxidants deteriorate during ageing of cells,
      or essential, unrepairable damages are imparted to the cell by
      oxidants regardless of the activity of antioxidant defence systems.
      The many reports dealing with a putative breakdown in antioxidant
      defence systems failed to positively support this postulate.
      However, a minor depletion in cellular glutathione by exposure to a
      model lipophilic peroxide led to a significant decrement in DNA and
      protein synthesis. In other words, the glutathione redox cycle is
      intrinsically fallible with respect to defending the cellular DNA
      replication system against this model lipophilic peroxide.
      Interestingly, after ageing in culture cells a partial uncoupling of
      the NADPH-producing and -consuming systems tends to take place.
      Experiments involving the addition of antioxidants to the culture
      medium have failed to significantly extend the lifespan of cultured
      diploid somatic cells. The level of antioxidants appears to be a
      modulator rather than a primary determinant of cellular ageing in
      culture. Several lines of evidence suggest that DNA damages
      accumulate during ageing of the organism, but no oxidant-related DNA
      damage has been pinpointed in the cultured cell system. Human
      mutants with defects in antioxidant enzymes have not shown
      conclusive signs of accelerated ageing. Cells from patients with
      Werner's syndrome (progeria of the adult), on the other hand, do not
      suffer from a defect in their antioxidant defence system, nor do
      they accumulate more than normal amounts of autofluorescent products
      resulting from lipid peroxidation. The recent finding that Werner's
      syndrome constitutes a mutator phenotype may prompt the comparison
      of oxidant- and ageing-related mutation spectra in order to
      investigate a mutational theory of ageing as a new derivative from
      the free radical hypothesis. [References: 118]

28
UI  - 92082155
AU  - Le Merrer M
AU  - Guillot M
AU  - Briard ML
AU  - Maroteaux P
IN  - U12, Unite de Recherches INSERM sur les Handicaps Genetiques de
      l'Enfant, Hopital des Enfants-Malades, Paris, France.
TI  - Lethal progeroid syndrome with osteolysis. Case report.
SO  - Annales de Genetique 1991;34(2):82-4
AB  - A particular progeroid syndrome with severe acro-osteolysis,
      cutaneous changes, failure to thrive, and early death is described
      in a young boy. Progeria and mandibulo-acral dysplasia are
      discussed, but early death is unusual in these two syndromes. This
      observation raises the question of a large spectrum including all of
      these syndromes.

29
UI  - 92080443
AU  - Gillar PJ
AU  - Kaye CI
AU  - McCourt JW
IN  - University of Texas Health Science Center, Department of Pediatrics,
      San Antonio 78284-7802.
TI  - Progressive early dermatologic changes in Hutchinson-Gilford
      progeria syndrome.
SO  - Pediatric Dermatology 1991 Sep;8(3):199-206
AB  - We describe evolving dermatologic findings in a male with progeria
      from age 1 month to 21.5 months. At 18 months of age, irregular
      pigmentary changes of the abdomen, early occipital alopecia,
      superficial scalp veins, glyphic nasal tip, absent ear lobules,
      coarse hair that stands on end, crowded dentition with delayed tooth
      development, and dystrophic nails permitted the diagnosis of
      progeria. Radiographs showed evidence of resorption of the distal
      ends of the clavicles, attenuation of the terminal phalanges,
      diffuse osteopenia, and fishmouth vertebral bodies, which are
      typical of this syndrome. Appreciation of the evolution of early
      dermatologic findings may permit earlier diagnosis of this condition
      in infants with skin changes.

30
UI  - 92059161
AU  - Cusano F
AU  - Scarano G
TI  - Familial progeria or mandibulo-acral dysplasia? [letter].
SO  - American Journal of Medical Genetics 1991 Oct 1;41(1):139

31
UI  - 92049501
AU  - Wang SM
AU  - Nishigori C
AU  - Yagi T
AU  - Takebe H
IN  - Department of Experimental Radiology, Faculty of Medicine, Kyoto
      University, Japan.
TI  - Reduced DNA repair in progeria cells and effects of gamma-ray
      irradiation on UV-induced unscheduled DNA synthesis in normal and
      progeria cells.
SO  - Mutation Research 1991 Jan;256(1):59-66
AB  - A reduction in the amount of UV-induced unscheduled DNA synthesis
      (UDS), and reduced cell survival and host-cell reactivation against
      UV exposure in Hutchinson-Gilford progeria syndrome cell strains
      were shown. UV-induced UDS in 4 progeria cell strains was 33-50% of
      the normal level. A similar reduction in the UV-induced UDS in
      normal cells was caused by gamma-ray irradiation to the cells before
      UV irradiation. The dose of gamma-rays required to cause a reduction
      in UDS of normal cells to the level of progeria cells was 40 Gy and
      the reduction was reversible after 2 days. In progeria cells,
      gamma-ray irradiation further reduced UDS with a lower gamma-ray
      dose required than in normal cells, and the reduction was also
      reversible but with less relative recovery than in normal cells. The
      presence of a 'built-in' defect in progeria cells responsible for
      the reduced DNA-repair capacity was suggested, and such defect may
      share a common mechanism with the reduction of UV-induced UDS in
      normal cells caused by gamma-ray irradiation.

32
UI  - 91276556
AU  - Gupte S
TI  - Progeria [letter; comment].
SO  - Indian Pediatrics 1991 Feb;28(2):196

33
UI  - 91202424
AU  - Yu QX
AU  - Zeng LH
IN  - Faculty of Stomatology, Sun Yat-Sen University of Medical Sciences,
      Guangzhou, China.
TI  - Progeria: report of a case and review of the literature. [Review]
SO  - Journal of Oral Pathology & Medicine 1991 Feb;20(2):86-8
AB  - A case of progeria is reported. The literatures in this topic is
      reviewed. The oral manifestation of the patients with progeria is
      summarized. [References: 26]

34
UI  - 91190559
AU  - Sood S
AU  - Rao RC
AU  - Ragav B
AU  - Berry M
IN  - Department of Radio-Diagnosis, All India Institute of Medical
      Sciences, New Delhi.
TI  - Progeria syndrome with characteristic deformation of proximal radius
      observed on CT.
SO  - Acta Radiologica 1991 Jan;32(1):67-8
AB  - The progeria syndrome (Hutchinson-Gilford) is an uncommon disease. A
      peculiar shape of the proximal radial metaphyseal region caused by
      an infolding of the cortex was observed on CT in 2 brothers
      suffering from this disorder, a feature not previously reported. A
      brief review of the radiologic literature was undertaken. This new
      observation needs to be further evaluated as it may provide a
      clinching diagnostic feature of this disease.