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952 records · Page 53Linked to original sources
PubMed1993

The impaired transcription factor AP-1 DNA binding activity in lymphocytes derived from subjects with some symptoms of premature aging.

The study of human disorders known as premature aging syndromes may provide insight into the mechanisms of cellular senescence. The main feature of cellular senescence in vitro is cessation of cell proliferation. Down syndrome (DS) and neuronal ceroid-lypofuscinosis (NCL) are clinically characterized by the premature onset of numerous features normally associated with human aging. Phytohemagglutinin stimulated lymphocytes derived from DS subjects showed a statistically significant diminished proliferation capacity in comparison with lymphocytes derived from NCL and healthy individuals. We demonstrated, by applying the electrophoretic mobility shift assay, slightly impaired AP-1 DNA binding activity in NCL lymphocytes and strong in DS ones. Our results showed that the same molecular mechanisms of proliferation cessation could exist in fibroblasts characterized by replicative senescence and in lymphocytes derived from individuals with premature aging syndromes (Down).

Adolescent↗
PubMed1993

Genetic defects in proteoglycan biosynthesis.

An overview on the structure of proteoglycans and on genetic defects in proteoglycan biosynthesis is given. Several patients with progeroid-like symptoms have been shown to have abnormalities in the biosynthesis of chondroitin/dermatan sulfate proteoglycans. A partial inactivity of galactosyltransferase I which catalyzes the second glycosyl transfer reaction in the assembly of glycosaminoglycan chains has been shown to represent the primary defect in one of the patients. A diminished concentration of a collagen-associated proteoglycan is considered to play a pathogenetic role in the development of loose skin.

Carbohydrate Sequence↗
PubMed1993

Deficient expression of decorin in infantile progeroid patients.

Fibroblasts from young patients exhibiting clinical features of progeroidal syndromes showed decreased biosynthesis of the small proteoglycan decorin. Cells in culture were metabolically labeled, and proteoglycans secreted into the medium were analyzed electrophoretically after immunoprecipitation with antibodies raised against decorin and biglycan. Fluorograms showed regularly a reduction to 15-30% of the normal amount of mature decorin and its core protein after chondroitin ABC lyase treatment. The size of the glycosaminoglycan chains was increased, but there was no obvious anomaly in the secretion kinetics of the mature proteoglycan. In addition, the patients' fibroblasts synthesized an increased amount of biglycan compared to control cells from healthy donors. Northern blot analysis clearly demonstrated a reduction by 85-94% in decorin mRNA, but biglycan mRNA was concomitantly increased, indicating that these alterations occur at the transcriptional level of protein expression. Transcription of decorin in fibroblasts from one of the patients was stimulated up to 3-fold by treatment with interleukin-1 beta. No response to interleukin-1 beta and transforming growth factor-beta was observed in the cells from another patient. In situ hybridization of cultured cells with an antisense decorin probe showed that decorin levels were reduced throughout the cell population. Surprisingly, subsequent examination of cells from one of the patients, now in mid-teenage, revealed a return to normal levels of decorin expression compared to age-matched controls. These studies suggest that, as in Marfan's syndrome where the primary defect concerns the fibrillin gene, reduced decorin expression contributes to the formation of an abnormal matrix and the pathogenesis of these disorders. They also indicate that this abnormality is likely to represent a secondary phenomenon which leads to a fault in the regulation of decorin gene transcription.

Base Sequence↗
PubMedDate not supplied

Effects of calcium channel blockers on impairment of brain function in senescence-accelerated mice.

The effects of the L-type calcium channel blockers, nicardipine, nimodipine, nilvadipine and amlodipine, on brain dysfunction were examined in senescence-accelerated-prone mice. A disturbed brain function in passive avoidance response, forced swimming, rota-rod and traction tests was observed in senescence-accelerated-prone mice compared to senescence-accelerated-resistant mice. A single oral administration of the four calcium channel blockers tested had little effect on the brain dysfunction in senescence-accelerated-prone mice. In contrast, the daily oral administration of nicardipine (1 and 3 mg/kg), nimodipine (3 mg/kg) and nilvadipine (3 mg/kg), once a day for three weeks, prolonged the shortened latency of step-through in the passive avoidance response and falling time in rota-rod tests. Brain dysfunction in forced swimming and traction tests was not influenced by repeated administration of these blockers. Repeated administration of amlodipine for three weeks in senescence-accelerated-prone mice showed little pharmacological actions in all four tests. Thus, we found that repeated administration of nicardipine, nimodipine and nilvadipine ameliorated the brain dysfunction in these mice. Furthermore, the present study suggests that senescence-accelerated-prone mice can be used as an appropriate model for evaluating the pharmacological effects of calcium channel blockers on brain dysfunction.

Amlodipine↗
PubMed1997

Premature aging syndrome with osteosarcoma, cataracts, diabetes mellitus, osteoporosis, erythroid macrocytosis, severe growth and developmental deficiency.

We describe a premature aging disorder in a 15-year-old girl with severe growth and developmental deficiency. Her clinical findings included osteosarcoma, nuclear and subcapsular cataracts, insulin-resistant diabetes mellitus, osteoporosis, epilepsy, foot ulcers, erythroid macrocytosis, and unusual facial appearance. Hyaluronic acid levels in serum and urine were normal. Cultured skin fibroblasts had a normal potential for in vitro growth. This finding represents a new and unique premature aging syndrome.

Abnormalities, Multiple↗
PubMed1997

New progeroid disorder.

We report on a 10-year-old Caucasian male with a prematurely aged appearance, delayed bone maturation and dental development, pronounced acro-osteolysis with brachydactyly, and distinctive cutaneous findings including hard, confluent skin lesions with some clinical and histologic resemblance to those of juvenile hyaline fibromatosis (JHF). He also had hyperopia, sensorineural hearing loss, and elevated TSH. Linear growth and intellectual functions were normal. We believe that this patient represents a new progeroid disorder.

Abnormalities, Multiple↗
PubMed1997

Genetics of ageing.

The classical arguments favouring a genetic basis of ageing are reviewed emphasizing the questions that remain unanswered. Genes cannot be the sole genetic determinants of ageing. Mendel's paradigm cannot anymore explain all the results recently obtained. Different aspects of the organization of the genome must also play a role in ageing. The functions of the largest part of the human genome remain unknown. Moreover the different genetic theories of ageing are based on natural selection. However, other paradigms are being proposed that can complement or replace Darwin's paradigm. They are based on the spontaneous organization of complex systems. They must be considered in the reappraisal of the ageing phenomenon.

Aging↗
PubMedDate not supplied

[Werner syndrome. Apropos of a case].

A 26 year-old woman, whose parents were consanguineously married, was admitted to our center because of bilateral juvenile cataract. The patient exhibited short stature, sclerodermalike appearance of the skin with a typical bird-like facies, thinning and graying of hair, high pitched voice and hypogonadism. Werner's syndrome, was diagnosed. History, pathogeny, clinical features, diagnosis and cataract surgery are discussed.

Adult↗