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Biomedical subjects

A Roy

Publications and source records attributed to A Roy.

At least 145 records · Page 8Linked to original sources

Human Prop-1: cloning, mapping, genomic structure. Mutations in familial combined pituitary hormone deficiency.

Prop-1 is a newly isolated pituitary-specific paired-like homeodomain transcription factor whose cDNA sequence is well known in mouse. To study its involvement in human combined pituitary hormone deficiency (CPHD), we have isolated the human cDNA ortholog and determined the exon/intron organization and chromosomal localization of the human gene. A Prop-1 defect was characterized in three CPHD families. One missense mutation (R73C) involves a residue conserved in 95% of the more than 400 homeodomain proteins so far identified; in vitro splicing assays demonstrated the functional importance of the second defect, whereas the remaining mutation is a frameshift. Given the disease phenotype documented in the patients, these data, which will facilitate molecular investigations in other patients, demonstrate the crucial role of Prop-1 in the proper development of somatotrophs, lactotrophs, thyreotrophs and gonadotrophs.

Amino Acid Sequence↗

Placebo-controlled study of sertraline in depressed recently abstinent alcoholics.

BACKGROUND: Depression is common among recently abstinent alcoholics; however, its treatment has been little studied. METHODS: Thirty-six depressed recently abstinent alcoholics were randomized in a 6-week double-blind placebo-controlled trial of sertraline 100 mg daily. RESULTS: There was a significant group x time interaction for both the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI). For the HDRS there were significant differences between the sertraline and placebo groups at weeks 3 and 6 and for the BDI at week 3. Also, patients receiving sertraline had significantly lower mean posttreatment HDRS and BDI scores than patients receiving placebo. Furthermore, significantly more of the patients receiving sertraline obtained a Clinical Global Impression rating of "very much improved." CONCLUSIONS: Depressed recently abstinent alcoholics benefit from antidepressant medication.

Adult↗

Lactate, lactate/pyruvate ratio and catecholamine interrelations in cord blood at delivery in complicated pregnancies.

The interrelationships between lactate, lactate/pyruvate (L/P) ratio and catecholamines (CA) in cord artery and vein blood were studied in 56 pregnancies who had complications in the antenatal period or during labour. This group of babies had higher CA levels and were more acidaemic than fetuses after normal pregnancies and labour. There were stronger correlations between lactate and noradrenaline (NA) (R = 0.56, P < 0.001), adrenaline (A) (R = 0.41, P = 0.002) and dopamine (DA) (R = 0.42, P = 0.001) in cord artery blood, than previously reported for normal deliveries. Correlations between L/P ratio and CAs were also significant, although weaker. Multiple regression analysis, using cord artery lactate as the dependent variable, revealed significant correlations for pH (P = 0.01) and pyruvate (P < 0.001) but not for the CAs. The subgroups with high lactate (> 75th centile) had significantly higher NA (P = 0.007) and DA (P < 0.001) in cord artery and NA (P < 0.001) and A (P < 0.001) in cord vein blood, as compared with the subgroup who had lower lactate concentrations. We conclude that fetal hypoxia induces fetal CA production as well as anaerobic metabolism with lactate production. However, the adrenergic stimulation seems not to contribute significantly to the fetal lactate production.

Asphyxia Neonatorum↗

High PCO does not alter pHi, but raises [Ca2+]i in cultured rat carotid body glomus cells in the absence and presence of CdC12.

We measured the effect of high PCO (500-550 Torr) on the pHi and [Ca2+]i in cultured glomus cells of adult rat carotid body (CB) as a test of the two models currently proposed for the mechanism of CB chemoreception. The metabolic model postulates that the rise in glomus cell [Ca2+]i, the initiating reaction in the signalling pathway leading to chemosensory neural discharge, is due to [Ca2+] release from intracellular Ca2+ stores. The membrane potential model postulates that the rise in [Ca2+]i comes from influx of extracellular Ca2+ through voltage-dependent Ca2+ channels (VDCC) of the L-type. High PCO did not change pHi at PO2 of 120-135 Torr, showing that CO-induced changes in [Ca2+]i are not due to changes in pHi. High PCO caused a highly significant rise in [Ca2+]i from 90+/-12 nM to 675+/-65 nM, both in the absence and in the presence of 200 microM CdCl2, a potent blocker of L-type VDCCs. This result is fully consistent with release of Ca2+ from glomus cell intracellular stores according to metabolic model, but inconsistent with influx of extracellular Ca2+ through VDCCs according to the membrane potential model.

Animals↗

K+-current modulated by PO2 in type I cells in rat carotid body is not a chemosensor.

According to the membrane channel hypothesis of carotid body O2 chemoreception, hypoxia suppresses K+ currents leading to cell depolarization, [Ca2+]i rise, neurosecretion, increased neural discharge from the carotid body. We show here that tetraethylammonium (TEA) plus 4-aminopyridine (4-AP) which suppressed the Ca2+ sensitive and other K+ currents in rat carotid body type I cells, with and without low [Ca2+]o plus high [Mg2+]o, did not essentially influence low PO2 effects on [Ca2+]i and chemosensory discharge. Thus, hypoxia may suppress the K+ currents in glomus cells but K+ current suppression of itself does not lead to chemosensory excitation. Therefore, the hypothesis that K+-O2 current is linked to events in chemoreception is not substantiated. K+-O2 current is an epiphemenon which is not directly linked with O2 chemoreception.

4-Aminopyridine↗

Correlation between stationary phase survival and acid trehalase activity in yeast.

The levels of two trehalose hydrolysing enzymes, acid trehalase (AT) and neutral trehalase (NT), have been investigated in Candida utilis at different stages of growth; in complete contrast to Saccharomyces cerevisiae, significant AT activity appears to be absent at all stages of growth studied in C. utilis. In addition, presence of only very low amounts of iso-aspartyl methyl transferase (IMT) activity at the onset of stationary phase and lower survival ability in early stationary phase in contrast to that of S. cerevisiae lend support to the ideas that (a) lower degree of survival of C. utilis in the stationary phase may be a direct consequence of inability to mobilise stored trehalose due to absence of intracellular AT and reduced levels of IMT activities and (b) trehalose may have a dual role vis-à-vis stress resistance in yeasts.

Candida↗

Suppression of glomus cell K+ conductance by 4-aminopyridine is not related to [Ca2+]i, dopamine release and chemosensory discharge from carotid body.

The hypothesis that suppression of O2-sensitive K+ current is the initial event in hypoxic chemotransduction in the carotid body glomus cells was tested by using 4-aminopyridine (4-AP), a known suppressant of K+ current, on intracellular [Ca2+]i, dopamine secretion and chemosensory discharge in cat carotid body (CB). In vitro experiments were performed with superfused-perfused cat CBs, measuring chemosensory discharge, monitoring dopamine release by microsensors without and with 4-AP (0.2, 1.0 and 2.0 mM in CO2-HCO3- buffer) and recording [Ca2+]i by ratio fluorometry in isolated cat and rat glomus cells. 4-AP decreased the chemosensory activities in normoxia but remained the same in hypoxia and in flow interruption. It decreased the tissue dopamine release in normoxia, and showed an additional inhibition with hypoxia. Also, 4-AP did not evoke any rise in [Ca2+]i in glomus cells either during normoxia and hypoxia, although hypoxia stimulated it. Thus, the lack of stimulatory effect on chemosensory discharge, inhibition of dopamine release and unaltered [Ca2+]i by 4-AP are not consistent with the implied meaning of the suppressant effect on K+ current of glomus cells.

4-Aminopyridine↗

Novel implications of the potential role of selenium on antioxidant status in streptozotocin-induced diabetic mice.

Levels of blood glucose, lipid peroxidation, glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase (GST) activities and blood selenium levels were determined in streptozotocin (STZ)-induced diabetic mice. The effect of oral administration of sodium selenite was studied on the above parameters. Diabetes caused hyperglycemia (2.8-fold increase) with a significant increase in the malondialdehyde levels (89% in liver and 83% in blood) and GST activity (55%) and marked decreases in GSH levels (approximately 73% in blood and 79% in liver) in the 5th week after STZ treatment as compared to normal control animals. Treatment of STZ-induced diabetic mice with sodium selenite changed these parameters to near control values in almost all cases. These results suggest that selenium plays a role in reducing the oxidative stress associated with diabetes.

Animals↗

Is introversion a risk factor for suicidal behaviour in depression?

BACKGROUND: Personality is an important determinant of suicidal behaviour. However, it has been studied little in relation to suicidal behaviour in depression. METHODS: Depressed patients who had attempted suicide (N = 41) were compared with depressed patients who had never attempted suicide (N = 56) and normal controls (N = 56) for their scores on three personality questionnaires. RESULTS: Introversion was the only personality dimension where the post hoc test showed a different pattern between the two groups of depressed patients in their relation to controls. In particular, only depressed patients who had attempted suicide had significantly lower introversion scores than controls. CONCLUSION: The personality dimension of introversion may be a risk factor for suicidal behaviour in depression.

Adult↗

Stochastic response surface methods (SRSMs) for uncertainty propagation: application to environmental and biological systems.

Comprehensive uncertainty analyses of complex models of environmental and biological systems are essential but often not feasible due to the computational resources they require. "Traditional" methods, such as standard Monte Carlo and Latin Hypercube Sampling, for propagating uncertainty and developing probability densities of model outputs, may in fact require performing a prohibitive number of model simulations. An alternative is offered, for a wide range of problems, by the computationally efficient "Stochastic Response Surface Methods (SRSMs)" for uncertainty propagation. These methods extend the classical response surface methodology to systems with stochastic inputs and outputs. This is accomplished by approximating both inputs and outputs of the uncertain system through stochastic series of "well behaved" standard random variables; the series expansions of the outputs contain unknown coefficients which are calculated by a method that uses the results of a limited number of model simulations. Two case studies are presented here involving (a) a physiologically-based pharmacokinetic (PBPK) model for perchloroethylene (PERC) for humans, and (b) an atmospheric photochemical model, the Reactive Plume Model (RPM-IV). The results obtained agree closely with those of traditional Monte Carlo and Latin Hypercube Sampling methods, while significantly reducing the required number of model simulations.

Air Pollutants↗

Reversible neuropathy in chronic renal failure.

Chronic renal failure is associated with distal symmetrical axonal neuropathy. We report a 50-year-old man who suffered from chronic renal failure due to benign enlargement of the prostate. He presented with fever and rapidly developing pure motor neuropathy. The nerve conduction velocity was slow and the F response delayed, suggestive of demyelinating neuropathy. A sural nerve biopsy specimen was also consistent with demyelination and axonal changes. This patient improved significantly following intermittent catheterization and a short course of norfloxacin. Renal failure may be associated with reversible motor neuropathy.

Axons↗

Electroretinogram in withdrawn cocaine-dependent subjects. Relationship to cue-elicited craving.

BACKGROUND: We have previously reported that people who are cocaine-dependent have reduced blue cone b-wave electroretinogram (ERG) responses. In this preliminary study, we examined the relationship between blue cone ERG amplitudes and craving response to cocaine cues. METHOD: A new series of 14 recently withdrawn subjects who were cocaine-dependent completed a cocaine craving questionnaire at baseline, and again following exposure to laboratory cues; an ERG was also performed. RESULTS: Cocaine-dependent subjects with a blunted ERG blue cone response (< 0.5 microV) showed significantly greater increases in craving following cue-exposure than subjects without the blunted ERG blue cone response. CONCLUSIONS: Subjects with a blunted ERG response may represent a subgroup more vulnerable to cocaine craving and relapse.

Adult↗

Accumulation of chlorpyrifos on residential surfaces and toys accessible to children.

Quantitative examination of major pathways and routes of exposure to pesticides is essential for determining human risk. The current study was conducted in two apartments and examines the accumulation of the pesticide chlorpyrifos in childrens' toys after the time suggested for reentry after application. It has been established for the first time that a semivolatile pesticide will accumulate on and in toys and other sorbant surfaces in a home via a two-phase physical process that continues for at least 2 weeks postapplication. A summation of the above for a 3-6-year-old child yielded an estimated nondietary total dose of 208 microg/kg/day. Potential exposure from the inhalation pathway was negligible, while dermal and nondietary oral doses from playing with toys contributed to 39 and 61% of the total dose, respectively. If children with high frequency mouthing behavior are considered as candidates for acute exposure to chlorpyrifos residues, the estimated acute dose could be as high as 356 microg/kg/day. Routine reapplication of pesticides could lead to continued accumulation in toys and other sorbant surfaces, e.g., pillows, with large sorbant reservoirs, which can become a long-term source of exposure to a child. Estimates of a child's nondietary exposure to chlorpyrifos associated with toys and other sorbant surfaces for a period of 1 week following application appear to be of public health concern, and studies of actual childhood exposure from this pathway are warranted in the home environment. The above information should be used to determine if current procedures for postapplication reentry are sufficient and to evaluate the need for procedures to store frequently used household toys, pillows, and other sorbant objects during insecticidal application.

Air Pollution, Indoor↗

Quality assessment of two lactate test strip methods suitable for obstetric use.

Accuracy of lactate determinations in cord blood was tested for one reflectometric (Accusport) and one amperometric (Lactate Pro) microvolume test strip lactate meter. Both meters, using a whole blood sample, measure lower levels of lactate than a reflectometric device considered as a reference method, which analyses lactate in plasma. Readings were unaffected irrespective of lactate concentrations for the Lactate Pro, whilst the Accusport overestimated low lactate concentrations and underestimated high values. Both lactate meters underestimated lactate concentrations at high hematocrits, as compared with the reference method. The Lactate Pro has a fixed sample volume of 5 microliters while the Accusport uses random blood drop as sample volume. However, in analyses with less than 20 microliters sample volume considerable underestimation was found with the Accusport. Coefficient of variation was 3.8-8.9% for the Accusport and 3.1-4.0% for the Lactate Pro within lactate concentrations between 2.1 and 5.3 mmol/l. The amperometric device, the Lactate Pro, performed best in these tests dealing with fetal blood lactate concentrations. The new technique can be a useful tool in perinatal research as well as in obstetric practice.

False Negative Reactions↗

A longitudinal study of sero-reactivity to Plasmodium falciparum antigen in children and adult living in an endemic area of U.P.

Antibody levels of Pf RESA derived peptide R1 (EENVEHDA-C) from individuals living in malaria endemic areas correlated well with levels of endemicity. Serological and parasitological investigations were done in 32 adults (> 20 yrs) and 35 children (2-5 yrs) for three years; i.e. from 1992-95 periodically in village Piyawoli, U.P. Antibody levels against R1 peptide was estimated by ELISA, and blood smear for P. falciparum and P. vivax were screened using Jaswant Singh-Bhattacharya (JSB) staining. It appeared from our investigations that anti-R1 antibodies had a short span of life, i.e. 6-9 months. The longevity of these antibodies do not differ much in adults and children. The studies do not indicate any protective role for these antibodies. However, the levels of anti-R1 antibodies in a population living under malariogenic condition are related to Pf malaria endemicity.

Adult↗