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S Vyas

Publications and source records attributed to S Vyas.

At least 19 recordsLinked to original sources
PubMed1992

Decreased choline acetyltransferase mRNA expression in the nucleus basalis of Meynert in Alzheimer disease: an in situ hybridization study.

The subnormal choline acetyltransferase (ChoAcTase) activity in the cerebral cortex of patients with Alzheimer disease (AD) is thought to originate from the loss of cholinergic neurons in the nucleus basalis of Meynert (nbM). To examine possible changes in the functional activity of the remaining cholinergic neurons in the nbM of patients with AD, the level of expression of ChoAcTase mRNA was evaluated. A procedure for double-labeling cholinergic neurons to detect ChoAcTase mRNA and the corresponding protein in the same cell was developed, taking advantage of an anti-ChoAcTase antibody and the recently isolated cDNA complementary to a sequence of the human ChoAcTase mRNA. In the study of three controls and four patients with AD, the presence of both ChoAcTase mRNA and protein was observed in the same large neurons in both nbM and putamen. Specificity of in situ hybridization was further supported by the absence of neuronal staining with a sense probe. In AD patients a subnormal level of expression of ChoAcTase mRNA per cholinergic cell was detected in the nbM but not in the putamen. Our data support the hypothesis that expression of ChoAcTase mRNA might be down-regulated in the surviving cholinergic neurons in the nbM of patients with AD, raising the possibility of functional restoration by stimulating ChoAcTase synthesis.

Alzheimer Disease↗
PubMed1992

AP-1 complex and c-fos transcription are involved in TPA provoked and trans-synaptic inductions of the tyrosine hydroxylase gene: insights into long-term regulatory mechanisms.

We have previously shown that the phorbol ester, TPA, which activates protein kinase C, causes, in PC12 cells, a transcriptional activation of tyrosine hydroxylase (TH), the key enzyme in catecholamine synthesis. The study has now been extended to examine the processes that underlie this transcriptional stimulation and, in addition, to seek whether similar mechanisms are involved in long-term trans-synaptic induction of the TH gene in adrenal medullae of rats that have been given a single injection of reserpine. In both systems, it was found that the induction of c-fos gene transcription was associated with that of the TH gene but with different kinetics. The promoter of the TH gene contains (at position -207/-200) a sequence (TGATTCA) which differs from the consensus TRE or AP-1 site (TGACTCA) by one nucleotide. Experiments were carried out to investigate whether the AP-1 protein complex which is known to contain Fos and Jun binds to the putative TRE region of the TH promoter. In the gel shift assays, the nuclear protein extracts derived from TPA-treated PC12 cells and from AM of reserpine injected rats displayed a higher magnitude of binding to a 25-mer TRE-TH oligonucleotide as compared to controls. The results showed that the behaviour of TRE-TH was atypical in that two retarded complexes (A and B) were observed, which were displaced by specific competitors. Trans-activation experiments with plasmids TRE-TH/TK/CAT and -754/-19 TH/pUC18-CAT in PC12 cells showed an increase in CAT activity in response to TPA that correlates with the previously observed increase in TH transcriptional activity by TPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Toxic effects of iron for cultured mesencephalic dopaminergic neurons derived from rat embryonic brains.

Iron, a transition metal possibly involved in the pathogenesis of Parkinson's disease, was tested for its toxic effects toward cultures of dissociated rat mesencephalic cells. When cultures were switched for 24 h to serum-free conditions, the effective concentrations of ferrous iron (Fe2+) producing a loss of 50% of dopaminergic neurons, as quantified by tyrosine hydroxylase (TH) immunocytochemistry, TH mRNA in situ hybridization, and measurement of TH activity, were on the order of 200 microM. High-affinity dopamine (DA) uptake, which reflects integrity and function of dopaminergic nerve terminals, was impaired at significantly lower concentrations (EC50 = 67 microM). Toxic effects were not restricted to dopaminergic neurons inasmuch as trypan blue dye exclusion index and gamma-aminobutyric acid uptake, two parameters used to assess survival of other types of cells present in these cultures, were also affected. Protection against iron cytotoxicity was afforded by desferrioxamine and apotransferrin, two ferric iron-chelating agents. Normal supplementation of the culture medium by serum proteins during treatment was also effective, presumably via nonspecific sequestration. Potential interactions with DA were also investigated. Fe2+ at subtoxic concentrations and desferrioxamine in the absence of exogenous iron added to the cultures failed to potentiate or reduce DA cytotoxicity for mesencephalic cells, respectively. Transferrin, the glycoprotein responsible for intracellular delivery of iron, was ineffective in initiating selective cytotoxic effects toward dopaminergic neurons preloaded with DA. Altogether, these results suggest (a) that ferrous iron is a potent neurotoxin for dopaminergic neurons as well as for other cell types in dissociated mesencephalic cultures, acting likely via autoxidation into its ferric form, and (b) that the presence of intra- and extracellular DA is not required for the observed toxic effects.

Animals↗
PubMed1991

Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause.

The protection afforded by postmenopausal oestrogen replacement against cardiovascular disease is not fully explained by changes in plasma lipoproteins. To investigate the effect of oestrogen on arterial tone, Doppler ultrasound was used to assess blood flow characteristics in the internal carotid arteries of 12 postmenopausal women. Patients were studied pretreatment and at weeks 4, 6, 9, and 22 of therapy with transdermal oestradiol 50 micrograms/day. The pulsatility index (PI), which is thought to represent impedance to blood flow distal to the point of sampling, was measured from the flow velocity waveform. 11 of the 12 patients were within 5 years of menopause; 1 was 8 years postmenopausal but had experienced bleeding 4 years after menopause. In the 11 women there was a highly significant correlation (r = 0.77) between time since menopause and baseline PI. A similar correlation (r = 0.74) was observed when the episode of postmenopausal bleeding was redefined as time of menopause in the twelfth patient. For all 12 patients, there was a significant negative correlation (r = -0.70) between change in PI during transdermal oestradiol therapy and mean of baseline plus week 22 PI value. For all correlations between changes in PI and time since menopause, the longer the time the greater the fall in PI. These results, and previous observations of a reduction in uterine artery PI with oestradiol treatment, suggest that oestrogen has a generalised effect on the arterial system.

Administration, Cutaneous↗
PubMed1991

Relations between the fetal circulation and pituitary-thyroid function.

OBJECTIVE: To study the relation between changes in the fetal thyroid hormone and thyroid stimulating hormone (TSH) concentrations and alterations in the fetal circulation as assessed by Doppler ultrasound. DESIGN: A cross-sectional study of small for gestational age (SGA) and red-cell isoimmunized fetuses undergoing cordocentesis and Doppler studies for the assessment and determination of fetal karyotype, acid-base balance and haemoglobin concentration. SETTING: Harris Birthright Research Centre for Fetal Medicine, King's College, London. SUBJECTS: 38 growth retarded and 38 red-cell isoimmunised fetuses. INTERVENTIONS: Cordocentesis. MAIN OUTCOME MEASURES: Serum TSH total and free thyroxine (T4, FT4) and total and free triiodothyronine (T3, FT3) concentrations; middle cerebral artery (MCAVm) and descending thoracic aorta (AoVm) mean blood velocities; fetal Po2 and haemoglobin concentration (Hb). RESULTS: Delta values (delta) calculated as the number of SDs from the respective normal mean for gestation were used to compare the results with those from a previous study of normal fetuses. Mean AoVm was increased in the isoimmunized fetuses (P less than 0.001) but decreased in the SGA fetuses (P less than 0.001). Mean MCAVm was increased in both groups (P less than 0.01; P less than 0.001). There were significant associations between the gestational age adjusted values for TSH and MCAVm (r = 0.23, P less than 0.05) and between T4, FT4 or FT3 and AoVm (r = 0.41, P less than 0.01; r = 0.50, P less than 0.01; r = 0.36, P less than 0.01 respectively). In addition, T4 and FT4 were associated with delta Po2 and delta Hb. CONCLUSION: In the hypoxaemic hypoxia of growth retardation and the anaemic hypoxia of rhesus disease there are significant associations between changes in fetal thyroid hormone concentrations and changes in fetal blood flow as assessed by Doppler. Irrespective of whether altered blood flow is the cause or effect of changes in thyroid hormone concentrations, the observed changes could have beneficial effects for fetal survival, in the presence of a hostile intrauterine environment.

Blood Circulation↗
PubMed1991

Effects of intrauterine growth retardation on postnatal visceral and cerebral blood flow velocity.

Blood flow velocity and pulsatility index were measured with Doppler ultrasound in the superior mesenteric artery, coeliac axis, and anterior cerebral artery in 18 very low birth weight, small for gestational age infants, and compared with findings from 18 weight matched, and 18 gestation matched, appropriate for gestational age controls. Mean velocity in the superior mesenteric artery was lower in the small for gestational age infants (15 cm/s) than in the gestation matched control group (20.4 cm/s). In those small for gestational age infants who had evidence of fetal hypoxia the mean velocity in the superior mesenteric artery was even lower (11.5 cm/s). There were no differences in velocity in the cerebral artery among the groups. Infants who were small for gestational age still had significantly lower superior mesenteric artery velocity than gestation matched controls at 1 week of age. The results suggest a specific reduction in visceral perfusion in infants who are small for gestational age and who have experienced fetal hypoxia, and this could predispose these infants to necrotising enterocolitis.

Aging↗
PubMed1991

Doppler investigation of the fetal circulation.

Doppler ultrasound provides a non-invasive method for the study of fetal haemodynamics. Animal studies on effects of hypoxia have provided evidence of a redistribution of cardiac output to favour perfusion of the fetal heart, adrenals and brain, at the expense of the carcass, gut and kidneys. This paper summarises the changes in fetal Doppler parameters with advancing gestation. Furthermore, it examines the alterations in fetal haemodynamics in relation to fetal blood oxygen tension in samples obtained by cordocentesis from small for gestational age (SGA) fetuses. In SGA fetuses increased downstream impedence to flow in the umbilical artery, as demonstrated by the absence of end-diastolic frequencies in the flow velocity waveforms (FVW), is associated with fetal hypoxia. This presumably reflects the underlying derangement of placental structure and function. The impedence to flow and mean blood velocity were also measured in FVWs from the descending thoracic aorta and common carotid artery, obtained by pulsed Doppler ultrasound, and from the middle cerebral and renal arteries obtained by colour flow imaging. There were significant correlations between the degree of fetal hypoxia and alterations in Doppler parameters, which were compatible with the brain sparing effect. Thus, in fetal hypoxia impedence to flow in the common carotid and middle cerebral arteries was decreased, whereas impedence in the aorta and renal artery was increased. There were simultaneous alterations in the mean blood velocity in the opposite direction to those in impedence.

Aorta, Thoracic↗
PubMed1991

In vitro and in vivo regulation of the expression of the tyrosine hydroxylase gene.

Preganglionic nerve stimulation has been shown to induce delayed or long term changes in the neuron. Different models were used to study the trans-synaptic regulation of the tyrosine hydroxylase (TH): the rat adrenal medulla (AM) and the superior cervical ganglia (SCG). Northern blot analysis, western blot and enzymatic assays demonstrated that the TH mRNA paralleled both an increase in the protein amount and its enzymatic activity. Results of in vitro transcription on nuclei isolated from AM or from SCG after treatment with reserpine suggest that this increase in TH expression is due to an effect on the transcriptional activity of the TH gene. Other gene, cfos, is also induced by reserpine indicating that the TH transcription in these neurons may be mediated by "third messengers". Several putative regulatory elements, in particular an octamer sequence AP1 has been localized in the promoter of TH gene. Gel shift assays with nuclear extracts from untreated and phorbol ester treated cells strongly suggest that a protein complex binds to this AP1 like sequence. Comparative analysis of gel shift assays with AM nuclear extracts exhibit a similar pattern suggesting that this AP1 site could be involved in the trans-synaptic regulation of TH.

Animals↗
PubMed1990

Transcriptional and post-transcriptional regulation of tyrosine hydroxylase gene by protein kinase C.

The role played by protein kinase C (PKC) in TH gene regulation was investigated at transcriptional and post-transcriptional levels using PC12 cells. The cells were treated with the phorbol ester TPA, which not only activates PKC but also causes down-regulation. PKC levels were monitored by [3H]PDBU binding assay and by using an anti-PKC antibody that detected intact PKC (79 kd) as well as its catalytic and regulatory domains. The [3H]PDBU binding to the membrane-associated PKC increased within 15-30 min of TPA treatment; thereafter total cellular [3H]PDBU binding decreased to a minimum of 20% of the control at 8 h. The rate of decrease in binding was greater than the decrease in the intensity of the staining of PKC holo enzyme visualized by anti-PKC antibody. TH mRNA levels, measured over the same time period, rose within 15 min of TPA treatment to peak at 4 h and subsequently declined below control level, paralleling the depletion of PKC. If cells depleted of PKC were reincubated in the normal medium, a recovery in PKC level was seen and, in parallel, TH mRNA levels increased to above control level. Furthermore, if down-regulation of PKC was prevented by incubating the cells with the protease inhibitor leupeptin, a decrease beyond control level in TH mRNA was not observed. TPA rapidly induced TH gene transcription; a maximal increase of two-fold was observed at 15 min, but the transcriptional rate then declined although it did not decrease beyond control values after 8 and 24 h of TPA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1990

Early sonographic diagnosis of body stalk anomaly.

Ultrasonographic features of a fetus at 18 weeks of gestation suggesting a body stalk anomaly are presented. These included a large abdominal anterior wall defect in apparent continuity with the placenta, severe kyphoscoliosis of the lower spine, the absence of one kidney, and a very short umbilical cord with only one umbilical artery. The amniotic fluid was reduced and the fetus was almost immobile at short-interval ultrasound examinations. The pregnancy was terminated and autopsy of the fetus showed abnormalities compatible with maldevelopment of both cephalic and caudal embryonic folds.

Abdominal Muscles↗
PubMed1990

Relation of rate of urine production to oxygen tension in small-for-gestational-age fetuses.

Hourly fetal urine production rate was determined by real-time ultrasonography immediately before cordocentesis for blood gas analysis in 27 small-for-gestational-age fetuses at 20 to 37 weeks' gestation; in 14 cases there was associated oligohydramnios. The values were compared with those of 101 appropriate-for-gestational-age fetuses. The hourly fetal urine production rate was significantly lower in the small-for-gestational-age fetuses than in the appropriate-for-gestational-age fetuses. Furthermore, there was a significant correlation between the degree of decrease in urine production and both the degree of fetal hypoxemia and the degree of fetal smallness. There was no significant difference between the oligohydramnios and nonoligohydramnios groups in either the degree of decrease in urine production or the degree of fetal hypoxemia.

Amniotic Fluid↗
PubMed1990

Doppler examination of the middle cerebral artery in anemic fetuses.

In 24 red cell isoimmunized pregnancies the fetal middle cerebral artery mean blood velocity increased with anemia. The blood velocity was not related to fetal blood PO2 and the relation of increased velocity to anemia was not affected by the pulsatility index. These findings suggest that the hyperdynamic circulation is a consequence of decreased blood viscosity.

Anemia↗
PubMed1990

Middle cerebral artery flow velocity waveforms in fetal hypoxaemia.

In 81 small-for-gestational age fetuses (SGA) colour flow imaging was used to identify the fetal middle cerebral artery for subsequent pulsed Doppler studies. Impedence to flow (pulsatility index; PI) was significantly lower, and mean blood velocity was significantly higher, than the respective reference ranges with gestation. Fetal blood sampling by cordocentesis was performed in all SGA fetuses and a significant quadratic relation was found between fetal hypoxaemia and the degree of reduction in the PI of FVWs from the fetal middle cerebral artery. Thus, maximum reduction in PI is reached when the fetal PO2 is 2-4 SD below the normal mean for gestation. When the oxygen deficit is greater there is a tendency for the PI to rise, and this presumably reflects the development of brain oedema.

Blood Flow Velocity↗
PubMed1990

Effects of protein kinase C down-regulation on secretory events and proopiomelanocortin gene expression in anterior pituitary tumor (AtT-20) cells.

To elucidate the role of the diacylglycerol-protein kinase C (PKC) pathway in beta-endorphin synthesis and secretion in anterior pituitary corticotrope tumor cells (AtT-20), a procedure for down-regulating PKC activity in the cells was developed. Treatment of AtT-20 cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) led to an increase in [3H]phorbol 12,13-dibutyrate binding to PKC in the membrane fraction of these cells 30 s after its addition to the culture medium. Thereafter, a decrease in both [3H]phorbol 12,13-dibutyrate binding and PKC-specific phosphotransferase activity occurred in a time- and dose-dependent manner in both the cytosolic and membrane fractions. For example, treatment of the cells with 100 nM TPA for 24 h resulted in an almost complete depletion of PKC activity. Immunoreactive beta-endorphin secretion was found to be stimulated two- to fourfold in the control cells after incubation with corticotropin-releasing factor (10(-7) M), forskolin (10(-6) M), or TPA (10(-7) M) for 4 h. In cells rendered PKC deficient, TPA-stimulated immunoreactive beta-endorphin release was abolished, forskolin-stimulated release was unaffected, and corticotropin-releasing factor-stimulated release was depressed. Treatment of control cells with any one of the three stimulatory agents led to an increase in proopiomelanocortin mRNA levels, and these responses were also depressed after TPA pretreatment. The results suggest that physiological processes thought to be entirely cyclic AMP dependent, such as corticotropin-releasing factor-elicited secretion, may be partially dependent on PKC-mediated biochemical events.

Animals↗
PubMed1989

Renal artery flow-velocity waveforms in normal and hypoxemic fetuses.

Color flow mapping was used to identify the fetal renal artery and to obtain flow-velocity waveforms. A reference range of the fetal renal artery pulsatility index with gestation was constructed from a cross-sectional study of 114 appropriate for gestational age fetuses of 17 to 43 weeks' gestation. The pulsatility index decreased linearly with gestation, indicating a fall in impedance to flow, and presumably an increase in renal perfusion. The renal artery pulsatility index was also determined in 18 small-for-gestational-age fetuses and was higher than the appropriate-for-gestational-age group. The small-for-gestational-age fetuses also had fetal blood sampling performed by cordocentesis. A significant, direct correlation was found between blood oxygen deficit and increased renal artery pulsatility index.

Blood Flow Velocity↗
PubMed1989

The use of color Doppler imaging for prenatal diagnosis of umbilical cord anomalies: report of three cases.

Color Doppler imaging could easily and rapidly detect the absence of an umbilical artery, despite the presence of oligohydramnios in one case and multiple cord loops involving a normal cord in the other case. In the third case, which on gray-scale imaging appeared as an indeterminate cystic structure of the cord, color Doppler imaging demonstrated a complex abnormal vascular pattern suggestive of an angiomyxoma.

Amniotic Fluid↗