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At least 19 recordsLinked to original sources
PubMed1991

Reduced DNA repair in progeria cells and effects of gamma-ray irradiation on UV-induced unscheduled DNA synthesis in normal and progeria cells.

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.

Adolescent↗
PubMed1991

Altered response of progeria fibroblasts to epidermal growth factor.

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.

Cell Division↗
PubMed1990

Altered regulation of platelet-derived growth factor A-chain and c-fos gene expression in senescent progeria fibroblasts.

The study of human genetic disorders known as premature aging syndromes may provide insight into the mechanisms of cellular senescence. These diseases are clinically characterized by the premature onset and accelerated progression of numerous features normally associated with human aging. Previous studies have indicated that fibroblasts derived from premature aging syndrome patients have in vitro growth properties similar to senescent fibroblasts from normal individuals. As an initial approach to determine whether gene expression is altered in premature aging syndrome fibroblasts, RNA was prepared from various cell strains and used for gel blot hybridization experiments. Although normal fibroblasts only express platelet-derived growth factor (PDGF) A-chain mRNA for a brief period following mitogenic stimulation, one strain of Hutchinson-Gilford (progeria) syndrome fibroblasts, AG3513, constitutively expresses PDGF A-chain mRNA and PDGF-AA homodimers. The PDGF A-chain gene does not appear to be amplified or rearranged in these fibroblasts. AG3513 progeria fibroblasts have properties characteristic of senescent cells, including an altered morphology and a diminished mitogenic response to growth promoters. The diminished response of AG3513 progeria fibroblasts to PDGF stimulation was examined in some detail. Studies using 125I-PDGF-BB, which binds with high affinity to both A- and B-type PDGF receptors, indicate that normal and AG3513 progeria fibroblasts have a similar number of PDGF receptors. Although receptor autophosphorylation occurs normally in PDGF-stimulated AG3513 progeria fibroblasts, c-fos mRNA induction does not. The senescent phenotype of AG3513 fibroblasts is probably unrelated to their constitutive PDGF A-chain gene expression; further studies are necessary in order to directly address this issue. Also, additional analysis of this progeria fibroblast strain may provide information on the control of mitogen-inducible gene expression in normal cells.

Adolescent↗
PubMed1986

Urinary hyaluronic acid elevation in Hutchinson-Gilford progeria syndrome.

The basic genetic defect in the Hutchinson-Gilford Progeria Syndrome (progeria), a premature aging syndrome, is unknown. To investigate possible defects in hyaluronic acid (HA) metabolism in this disease, the urinary excretion of HA was studied. Urine specimens from 11 patients with this disorder were examined for HA by a novel high performance liquid chromatography (HPLC) technique. In patients with progeria, HA excretion ranged from 169 micrograms HA/g creatinine to 1440 micrograms HA/g creatinine. In normal age-matched controls, HA excreted ranged from 0 to 77 micrograms HA/g creatinine. In all, a mean 17-fold increase in HA excretion was observed in patients with progeria when compared with age-matched normal controls. Total glycosaminoglycan (GAG) excretion was not elevated. Amongst normal controls, a modest age-related increase in HA excretion was observed. These results suggest that urinary HA levels are abnormally elevated in progeria.

Adolescent↗
PubMed1986

Elevation of urinary hyaluronic acid in Werner's syndrome and progeria.

Werner's syndrome and Hutchinson-Gilford progeria syndrome (progeria) are human genetic diseases which may serve as models for the study of premature aging. The basic defects underlying these diseases are unknown. An abnormally high level of urinary hyaluronic acid (HA) excretion has been previously reported in several Werner's and one progeria subject, all from Japan. To determine if a high HA level is a reliable marker for these diseases, we quantitated the urinary excretion of HA in three progeria subjects, one subject with an atypical progeroid syndrome, and a Werner's syndrome subject. Compared to controls, the total urinary HA was found to be markedly increased in the three progeria samples and in the Werner's syndrome sample. These findings support the previous observations indicating elevated HA may be a specific marker for these diseases.

Adolescent↗
PubMed1988

Elevated c-myc expression in progeria fibroblasts.

Protooncogene expression was determined in cultured human fibroblasts derived from donors diagnosed with Hutchinson-Gilford Syndrome (Progeria). An increased level of c-myc expression was noted in progeria cells compared to normal parental controls and unrelated, unaffected, age-matched controls. In two progeria cultures a 150% increase in c-myc expression was observed, while a third progeria culture, subsequently identified as a non-classic progeria showed a 45% increase in c-myc expression. Southern blot analysis did not indicate an amplification or translocation of the c-myc gene. No significant differences were found in the expression of the c-erbB or c-src protooncogenes.

Cells, Cultured↗
PubMed1992

Progeria: a human-disease model of accelerated aging.

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.

Basal Metabolism↗
PubMed1978

Phenylalanyl synthetase function in cultured fibroblasts from subjects with progeria.

Since progeria cells contain a diversity of altered proteins, some aspects of phenylalanyl synthetase function were examined in semipurified extracts of cultured skin fibroblasts using mixed rabbit tRNA as acceptor. No significant differences were found in the Km and Vmax for phenylalanine or ATP in progeria cells compared with controls. Initial velocities of both progeria and control synthetases were lower at late passage owing to either reduced enzyme content or reduced catalytic efficiency. Reverse phase 5 chromatography of tRNAs acylated by progeria and control synthetases gave a single peak of labeled phenylalanine tRNA in all cases with no secondary peaks evident. Total activity of phenylalanyl synthetase in progeria cells was similar to that of control cells at early passage while late-passage control cells had lower specific activities of these synthetases per unit protein.

Adenosine Triphosphate↗
PubMed1990

Hutchinson-Gilford progeria syndrome in siblings. Report of three new cases.

The Hutchinson-Gilford progeria syndrome is a rare, inherited, pediatric condition with features of premature and accelerated aging. The pattern of inheritance is uncertain though both autosomal dominant and autosomal recessive modes have been proposed. The patients usually present after the 1st year of life with progressive skin and skeletal changes that give rise to a characteristic physical appearance. Three siblings seen at the University of Benin Teaching Hospital are described in this report, the third documenting the occurrence of progeria in African black patients. The two older siblings show the classic physical and radiologic changes described in progeria whereas the third, a 2-year-old boy, manifests only the early physical and radiologic changes of the disease. We compare the radiologic features of progeria with those of other progeroid conditions: acrogeria, Werner's and Cockayne's syndromes.

Child↗
PubMedDate not supplied

Reduced DNA-repair capacity in cells originating from a progeria patient.

A Chinese boy was identified to be suffering from progeria (Hutchinson-Gilford syndrome), the first case of the disease ever reported in China. Cells originating from the patient had a reduced amount of unscheduled DNA synthesis after irradiation with ultraviolet light (UV). The fractions of the progeria cells surviving against UV irradiation measured by colony-forming ability, and the host-cell reactivation capacity of the progeria cells, measured by the plaque formation of UV-irradiated herpes simplex virus were lower than those measured in normal cells. The progeria cells appear to have a reduced capacity to repair UV excision damage.

Cells, Cultured↗
PubMed1976

Progeria: autopsy report of one case, with a review of pathologic findings reported in the literature.

An autopsy case of progeria associated with elastotic degeneration of the skin and preservation of the scalp hair, in a 20-year-old woman, is presented. The pathologic findings were scleroderma-like skin atrophy, elastotic degeneration of the skin, arteriosclerosis, atrophy of the endocrine glands, and acute peritonitis after appendectomy. In the reported cases of progeria, as in Werner's syndrome, no responsible parenchymatous organ has been identified. Rather, connective tissue, widely distributed throughout the entire body, may play an important role. The possible abnormal metabolism of connective tissue in progeria deserves further study.

Adult↗
PubMed1988

The musculoskeletal manifestations of progeria. A literature review.

Although a superficial similarity exists between the musculoskeletal disorders associated with natural aging and those of progeria, an in-depth analysis reveals profound differences in the pathophysiology between the two processes. The protean manifestations of progeria can best be explained on the basis of the vascular changes found at autopsy. A disorder of the vascular endothelium may predispose progeric vessels to atherosclerotic changes. The unique musculoskeletal manifestations of progeria arise from the effects of premature atherosclerosis on the vascularized connective tissues.

Bone and Bones↗
PubMed1990

[A case of progeria syndrome with cerebral infarction].

Cerebrovascular involvement is rare in progeria syndrome (Hutchinson-Gilford syndrome). A patient with progeria syndrome, who developed cerebral infarction, was reported. At 7 years of age, she suffered from right hemiplegia and transient ischemic attacks. X-ray CT showed multiple low density lesions in left frontal and parieto-occipital areas, which were enhanced with a contrast medium. Cerebral angiography demonstrated complete occlusion of left carotid artery and narrowing of vertebral artery. Brain imaging using 123I-N-isopropyl-p-iodoamphetamine (123I-IMP SPECT), which expressed regional cerebral blood flow, showed extensive perfusion defect over the left cerebral hemisphere in early scans, and redistribution phenomena in late scans. The symptoms improved gradually, which correlated well with 123I IMP-SPECT findings. This method will be useful to determine the prognosis as well as to understand changeable hemodynamic pathophysiology. A slowing of back ground on EEG also correlated well with clinical symptoms. It was necessary to examine the possibility of cerebrovascular involvement in progeria.

Amphetamines↗
PubMed1977

Progeria: a cell culture study and clinical report of familial incidence.

This report relates the case histories of two sisters who demonstrated the typical symptoms of progeria at birth. One of these children had died previous to this study. The familial occurrence underlines the thesis that progeria is an autosomal-recessive disorder. The examination of the cultured skin fibroblasts from the younger child showed a clear decrease in cell growth. On the other hand, the immunfluorescent examination of skin biopsies and cultured skin fibroblasts revealed no atypical distribution of collagen types.

Cells, Cultured↗
PubMed1991

Immortalization of Werner syndrome and progeria fibroblasts.

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.

Base Sequence↗
PubMed1992

Report on a case of Hutchinson-Gilford progeria, with special reference to orthopedic problems.

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.

Bone Diseases↗