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Biomedical subjects

S Vyas

Publications and source records attributed to S Vyas.

At least 37 records · Page 2Linked to original sources
PubMed1997

Expression of Bcl-2 in adult human brain regions with special reference to neurodegenerative disorders.

The expression of the protooncogene bcl-2, an inhibitor of apoptosis in various cells, was examined in the adult human brain. Several experimental criteria were used to verify its presence; mRNA was analyzed by northern blot with parallel experiments in mouse tissues, by RNase protection, and by in situ hybridization histochemistry. Bcl-2 protein was detected by western blot analysis and immunohistochemistry. Two bcl-2 mRNA species were identified in the human brain. The pattern of distribution of bcl-2 mRNA at the cellular level showed labeling in neurons but not glia. The in situ hybridization signal was stronger in the pyramidal neurons of the cerebral cortex and in the cholinergic neurons of the nucleus basalis of Meynert than in the Purkinje neurons of the cerebellum. Both melanized and nonmelanized neurons were labeled in the substantia nigra. In the striatum, bcl-2 mRNA was detected in some but not all neurons. In the regions examined for Bcl-2 protein, the expression pattern correlated with the mRNA results. In patients with Alzheimer's and Parkinson's diseases, quantification of bcl-2 mRNA in the nucleus basalis of Meynert and substantia nigra, respectively, showed that the expression was unaltered compared with controls, raising the possibility that the expression of other components of apoptosis is modulated.

Aged↗
PubMed1997

Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive cell loss confined mostly to dopaminergic neurons of the substantia nigra. Several factors, including oxidative stress, and decreased activity of complex I mitochondrial respiratory chain, are involved in the degenerative process. Yet, the underlying mechanisms leading to dopaminergic cell loss remain elusive. Morphological assessment for different modes of cell death: apoptosis, necrosis or autophagic degeneration, can contribute significantly to the understanding of this neuronal loss. Ultrastructural examination revealed characteristics of apoptosis and autophagic degeneration in melanized neurons of the substantia nigra in PD patients. The results suggest that even at the final stage of the disease, the dopaminergic neurons are undergoing active process of cell death.

Aged↗
PubMed1997

Apoptosis in dopaminergic neurons of the human substantia nigra during normal aging.

Morphological and biochemical alterations have been described in neurons of the aged human brain. However, the cell death process associated with neuronal senescence remains to be elucidated. Apoptosis and autophagic degeneration, two modes of programmed cell death described in embryogenesis and tissue renewal in adult, have been observed in nigral dopaminergic neurons in patients with Parkinson's disease. In the present study, we made the hypothesis that programmed cell death may be also involved in the death of nigral dopaminergic neurons occurring during aging. Cell death types were defined by morphological criteria identified at subcellular level. We thus performed an ultrastructural analysis in order to search for apoptotic and autophagic features in melanized neurons of the substantia nigra in four normal aged subjects. Morphological characteristics of apoptosis, such as contact loss with surrounding tissues, cell shrinkage and chromatin condensation, were found in 2% of the total number of melanized neurons analyzed. Although endoplasmic reticulum appeared normal, mitochrondria were markedly shrunken. Fragments of melanized neurons were found in glial cells. Autophagic degeneration or necrosis were not detected in melanized neurons. Signs of oxidative stress, such as vacuolation of mitochondria, were observed in melanized neurons devoid of apoptotic features. These findings demonstrate that apoptosis is involved in cell death of nigral dopaminergic neurons during normal aging. Since morphological abnormalities found in this study, such as marked mitochondrial shrinkage in apoptotic neurons, were not observed in patients with Parkinson's disease, the mechanisms underlying apoptosis may be different in aging and pathology.

Aged↗
PubMed1996

Cerebral and renal artery blood flow velocity before and after birth.

OBJECTIVE: To document perinatal changes in cerebral and renal artery haemodynamics in premature growth-retarded and normal term infants. DESIGN: Longitudinal study of individual infants. Doppler ultrasound measurements of blood flow velocity (BFV) in the middle cerebral and renal arteries were obtained before delivery, soon after delivery and during the first week of postnatal life. SETTING: Teaching hospital obstetric and neonatal units. SUBJECTS: 13 severely growth retarded infants born at 28-36 weeks gestation, and eight normally grown infants born at term. RESULTS: In both groups, BFV in the cerebral artery was significantly lower in the first few hours after birth than in fetal life, but subsequently increased to reach pre-delivery values by the end of the first week. In contrast, BFV in the renal artery during the first postnatal day was not significantly different from fetal values, but it also increased during the subsequent week. In six of the preterm growth-retarded infants, fetal blood gases were measured in samples obtained by cordocentesis, and in these cases an increase in blood oxygen content at birth was documented. CONCLUSIONS: Cerebral artery BFV falls at birth and is relatively low during the time that premature infants are at the greatest risk of developing periventricular haemorrhage.

Blood Flow Velocity↗
PubMed1996

Effect of gonadotrophin on cell and matrix retention and expression of metalloproteinases and their inhibitor in cultured human granulosa cells modelling corpus luteum function.

Granulosa cells were prepared from follicular aspirates obtained at oocyte collection for in-vitro fertilization (IVF) and maintained in culture. Substantial loss of cells from the culture surface occurred in the absence of gonadotrophin when cells were maintained on a thin layer of extracellular matrix (ECM) using a defined, serum-free medium. This cell loss was clearly and significantly reduced in the presence of human chorionic gonadotrophin (HCG) by days 4-6 of culture, and occurred in conjunction with loss of ECM. Analysis of culture medium by zymography using gelatin as substrate demonstrated the presence of metalloproteinases (MMP), MMP-9 (gelatinase B) appearing as the predominant band. Measurement of overall gelatinase activity in culture media revealed a progressive fall in gelatinase expressed on a per cell basis in media from HCG-treated cultures and this was less marked in controls. This suppression of gelatinase activity was consistent with an observed increase in production of tissue inhibitor of metalloproteinase-1 (TIMP-1) by HCG-treated cells, which was significant by days 6-8 of culture. We speculate that stabilization of the ECM may be an important aspect of HCG action in the corpus luteum.

Cells, Cultured↗
PubMed1995

Synergistic differentiation by chronic exposure to cyclic AMP and nerve growth factor renders rat phaeochromocytoma PC12 cells totally dependent upon trophic support for survival.

Chronic dibutyryl cAMP (dbcAMP) treatment was observed not only to potentiate the differentiating actions of nerve growth factor (NGF) in PC12 cells, but to render them completely dependent on trophic support for survival even in the presence of serum proteins. When both NGF and dbcAMP were withdrawn from doubly differentiated PC12 cultures, degenerative events occurred after a lag period of 12-18 h, and by 48 h < 5-10% of the cells remained viable. Reduction in [3H]dopamine uptake, an index of cell function and neurite integrity, paralleled cell demise. At the cellular level, approximately 20-30% of the nuclei exhibited clear signs of chromatin fragmentation, as characterized by propidium iodide staining, suggesting that degeneration occurred by apoptosis. The cells could be rescued completely from degeneration by dbcAMP or by other cAMP analogues, whereas NGF and depolarization were also effective, but only partially. Phorbol 12-myristate-13-acetate failed to afford protection. If deprivation was interrupted, cell demise could be stopped by restoration of initial culture conditions. Degenerative changes produced by deprivation and recovery processes were not inhibited by macromolecular synthesis inhibitors, e.g. cycloheximide and actinomycin-D. However, chronic addition of cycloheximide prior to deprivation greatly impaired the differentiation of NGF/dbcAMP cells, allowing these cells to withstand trophic support withdrawal. Altogether our results indicate that the cAMP transduction pathway plays a crucial role not only in the differentiation but also in the survival of NGF/dbcAMP PC12 cells.

Animals↗
PubMed1995

Effects of the picosecond neodymium:YLF laser on poly(methyl methacrylate) intraocular lenses during experimental posterior capsulotomy.

We evaluated the effect of the neodymium:YLF picosecond laser on intraocular lenses (IOLs) during experimental posterior capsulotomy and established the minimum damage threshold for lathe-cut poly(methyl methacrylate) (PMMA) IOLs. Single-piece, biconvex, lathe-cut PMMA lenses were placed in a model eye chamber against a latex membrane with a central area of lens-capsule touch. Energy levels from 40 micro J to 360 microJ pulse (0.4 mJ to 3.6 mJ) with a 0.5 mm line and a spot pattern were tested using different focal offsets. Threshold damage level was determined under the scanning electron microscope after observing the minimal energy level that did not cause damage to or pits in the IOLs. Lenses were then analyzed for size and type of damage. The 0.5 mm line pattern at 160 microJ using 350 microns offset was safe and effective for posterior capsulotomy in vitro. spot pattern caused IOL damage in the form of small pits at much lower energy levels of 80 microJ using 400 microns offset than the line pattern.

Lasers↗
PubMed1995

Trisomy 18: first-trimester nuchal translucency with pathological correlation.

Diagnosis of trisomy 18 was made following prenatal screening at 11 weeks' gestation for ultrasonographically detected nuchal translucency and subsequent chorionic villus sampling. An intact fetus was therapeutically aborted and pathological examination was undertaken. We conclude that, although the etiology of nuchal translucency remains unclear, it does not appear to be lymphatic or cardiac in origin.

Adult↗
PubMed1995

A Ewing's sarcoma cell line showing some, but not all, of the traits of a cholinergic neuron.

The Ewing's sarcoma cell line ICB 112 was examined in detail for a cholinergic phenotype. Choline acetyltransferase activity (12.3 +/- 2.9 nmol/h/mg of protein) was associated with the presence of multiple mRNA species labeled with a human choline acetyltransferase riboprobe. Choline was taken up by the cells by a high-affinity, hemicholinium-3-sensitive transporter that was partially inhibited when lithium replaced sodium in the incubation medium; the choline taken up was quickly incorporated into both acetylcholine and phosphorylcholine. High-affinity binding sites for vesamicol, an inhibitor of vesicular acetylcholine transport, were also present. The mRNAs for synaptotagmin (p65) and the 15-kDa proteolipid were readily detected and were identical in size to those observed in cholinergic regions of the human brain. Cumulative acetylcholine efflux was increased by raising the extracellular potassium level or the addition of a calcium ionophore, but the time course of stimulated efflux was slow and persistent. These results show that this morphologically undifferentiated cell line is capable of acetylcholine synthesis and expresses markers for synaptic vesicles as well as proteins implicated in calcium-dependent release but lacks an organized release mechanism.

Acetylcholine↗
PubMed1995

Long-term induction of tyrosine hydroxylase expression: compensatory response to partial degeneration of the dopaminergic nigrostriatal system in the rat brain.

The present study was undertaken to examine the adaptive changes occurring 1 and 6 months after moderate or severe unilateral 6-hydroxydopamine-induced lesions confined to the lateral part of the rat substantia nigra pars compacta (SNC). The expression of tyrosine hydroxylase (TH) enzyme was analyzed in the remaining dopaminergic nigral cell bodies and in the corresponding striatal nerve endings. In the cell bodies of the lesioned SNC, TH mRNA content was increased (+20 to +30%) 6 months after the lesion without changes in cellular TH protein amounts. The depletion of TH protein in the nerve terminal area was less severe than the percentage of cell loss observed in the SNC at 1- and 6-month postlesion intervals. Moreover, the decrease in TH protein in the ipsilateral striatum was less pronounced 6 months after lesion than 1 month after. That no corresponding change in TH protein content was observed in the cell bodies at a time when TH increased in nerve terminals suggests that the newly synthesized protein is probably rapidly transported to the striatal fibers. These results suggest the existence of a sequence of changes in TH expression between cell bodies and fibers, occurring spontaneously after partial denervation of the nigrostriatal pathway.

Adaptation, Physiological↗
PubMed1995

Postmenopausal oestrogens and arteries.

Postmenopausal oestrogen use is associated with a significant reduction in cardiovascular morbidity and mortality. The fact that a large scale controlled trial has not been conducted is a valid criticism, but the epidemiological data are compelling and there is evidence of biologically plausible mechanisms which may mediate this effect. Postmenopausal HRT also abolishes climacteric symptoms and conserves bone. For the postmenopausal woman who has had a hysterectomy, unless there are compelling reasons to the contrary, we believe that unopposed oestrogen therapy should be offered routinely. Women who still have a uterus (and these form the majority of potential HRT users) require oestrogens with cyclical progestogens. Whether such opposed therapy results in any reduction in cardiovascular protection needs to be addressed urgently. Meanwhile, it could be argued that these women should also be offered HRT routinely. Indeed, a recent consensus conference (Lobo & Speroff 1994) concluded that because of the magnitude of cardiovascular disease as a cause of morbidity and mortality, the beneficial role of estrogen in the primary prevention of cardiovascular disease in most women outweighs its potential risk. At the present time, there are insufficient data to indicate whether there are any groups of women for whom the risks may be too great to prescribe some form of estrogen therapy. As life expectancy increases in developed countries, such reductions in the leading cause of mortality are likely to benefit not only the individual woman, but the society in which she lives.

Cardiovascular Diseases↗
PubMed1994

Use of transvaginal ultrasonography with color Doppler imaging to determine an appropriate treatment regimen for uterine fibroids with a GnRH agonist before surgery: a preliminary study.

The aim was to obtain data that could be used to determine the most appropriate treatment regimen for uterine fibroids with a gonadotropin releasing hormone analog (goserelin) before surgery. Fifteen premenopausal women (aged 27-53 years; mean 40 years) were referred from a gynecological outpatients' clinic. They all had uterine fibroids and were awaiting hysterectomy or myomectomy. All women were scheduled to receive an implant of goserelin (3.6 mg), undergo transvaginal ultrasonography and have a sample of peripheral blood taken at monthly intervals for 6 months. The main outcome measures were fibroid size and indices of blood flow (the pulsatility index and peak systolic velocity) in both uterine arteries and the principal artery supplying the largest fibroid. The concentrations of follicle stimulating hormone, estradiol, luteinizing hormone and progesterone were measured in peripheral plasma. Twelve women (80%) completed 2 months of treatment, but only three (20%) completed the study (due to side-effects of the drug). After 2 months of treatment, the plasma hormone levels were all in the low-normal range; the mean fibroid volume had decreased by 53% and the mean peak systolic blood velocity in the fibroid artery had decreased by 45%. Mean changes in all indices were < 10% over the next 4 months of treatment. Six women (40%) had fibroids with an initial volume of > 100 ml; these tumors showed the largest reduction in size. We conclude that women with a uterine fibroid of > 100 ml are the best candidates for treatment with goserelin (3.6 mg/month) before surgery. Two months' treatment effects a marked reduction in fibroid volume and blood flow and is associated with good compliance.

Journal Article↗
PubMed1994

Induction of calbindin-D 28K gene and protein expression by physiological stimuli but not in calcium-mediated degeneration in rat PC12 pheochromocytoma cells.

To understand the role of calbindin-D 28K in neuronal degeneration, we examined its expression in differentiated PC12 cells in response to calcium intoxication, using the ionophore A23187 treatment, that results in cell degeneration and death. We first established that calbindin-D 28K is expressed in PC12 cells. The amounts of calbindin-D 28K mRNA and protein were increased by the differentiation factors, NGF and retinoic acid, but not by vitamin D3. Calbindin-D 28K expression was also significantly up-regulated by stimuli (depolarization, low concentrations of Ca2+ ionophore A23187) which increase intracellular calcium levels within the physiological range. In contrast, the calbindin-D 28K mRNA and protein concentrations were not modulated by high concentrations of A23187, which resulted in cell degeneration and death. Experiments with the antisense oligonucleotides showed that, although the calbindin-D 28K protein levels were decreased significantly, the progression of degenerative changes induced by calcium via A23187, was not altered.

Animals↗
PubMed1994

Morphological and molecular characterization of the response of differentiated PC12 cells to calcium stress.

The mechanisms that lead ultimately to neuronal death in pathological ageing of the brain remain mostly unknown as in the case of Parkinson's disease where there is a progressive and selective loss of dopaminergic neurons within the substantia nigra. Dopamine-expressing PC12 cells that were neuronally differentiated by nerve growth factor treatment were chosen as a culture model in which to study some of the changes that may occur during the course of the degenerative process. They were exposed to the calcium ionophore A23187 in order to produce a sustained rise in cytoplasmic calcium, a phenomenon related to various pathological conditions. The degenerative effects of the ionophore were dose- and time-dependent. They were characterized by early fragmentation of the neurites followed ultimately by a loss in cell viability. Biochemical changes, such as a decrease in [3H]dopamine uptake and modulations of the tyrosine hydroxylase gene, were detected before macroscopic evidence of cell suffering (e.g. neurite fragmentation) could be observed. Although an ongoing degenerative process was occurring in cell somata, PC12 cells were able to recover upon ionophore withdrawal. Characteristics of apoptosis such as chromatin condensation and DNA fragmentation were detectable in a small population of dying cells. DNA fragmentation could be prevented by the endonuclease inhibitor aurintricarboxylic acid. New protein synthesis was not required, as cycloheximide failed to prevent degeneration. Taken together, these results suggest that differentiated PC12 cells react to calcium stress through a sequence of regulatory processes which appears to be independent of the apoptotic pathway.

Animals↗
PubMed1994

Are hip fractures caused by falling and breaking or breaking and falling? Photoelastic stress analysis.

The distribution of stress in the heads of femurs has been assessed using an engineering technique known as photoelastic stress analysis. The aim of the investigation was to locate and evaluate the probable sites of structure failure in femurs with various axes of loading. The analysis shows that the maximum stress in the upper femur occurs in the cervical region during vertical loading. Lateral loading does not produce significant stress patterns at the sites of extracapsular hip fracture. It is concluded that cervical hip fractures in individuals suffering from osteoporosis result from a combination of fatigue damage and axial muscular compression, rather than forces generated by a fall. This has significance for the medico-legal interpretation of the cause of death following femoral neck fracture.

Accidental Falls↗