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Biomedical subjects

A Bhatt

Publications and source records attributed to A Bhatt.

At least 19 recordsLinked to original sources
PubMed2004

Stem cell research and transplantation: science leading ethics.

One of the most exciting developments in the biological sciences in the past decade has been the discovery and characterization of human embryonic stem cells (ESCs). The interest to transplanters is the potential applications of stem cells in regenerative medicine (RM), which may involve tissue engineering, genetic engineering, and other techniques to repair, replace, or regenerate failing tissues and organs. There is little controversy surrounding human adult stem cells. However, human ESCs are surrounded by a number of ethical controversies, the extent of which is partly dependent on their source. Those derived from currently existing embryonic stem cell lines are less controversial than those derived from "excess" embryos from in vitro fertilization (IVF) clinics, while ESCs derived from IVF embryos specifically created for the purpose are not acceptable to many people arguing from religious and other moral perspectives. Somatic cell nuclear transfer, or therapeutic cloning, must be distinguished from reproductive cloning. It holds the most promise for regenerative medicine. ESCs can also be derived from gonadal ridges of aborted fetuses. The transplant community must strive to uphold societal values in its effort to find remedies for their ailing patients and address the perennial problem of organ shortage. Transplanters also have a responsibility to engage the public in their efforts to gain public understanding and support, and policy makers must take into account public opinion. Only in this way can we realize the great potential of stem cell research for organ transplantation.

Embryo, Mammalian↗
PubMed2001

Alanine scan mutagenesis of the switch I domain of the Caulobacter crescentus CgtA protein reveals critical amino acids required for in vivo function.

The Caulobacter crescentus CgtA protein is a member of the Obg/GTP1 subfamily of monomeric GTP-binding proteins. In vitro, CgtA displays moderate affinity for both GDP and GTP and displays rapid exchange rate constants for either nucleotide, indicating that the guanine nucleotide-binding and exchange properties of CgtA are different from those of the well-characterized Ras-like GTP-binding proteins. The Obg/GTP1 proteins share sequence similarity along the putative effector-binding domain. In this study, we examined the functional consequences of altering amino acid residues within this conserved domain, and identified that T193 was critical for CgtA function. The in vitro binding, exchange and GTP hydrolysis of the T192A, T193A and T192AT193A mutant proteins was examined using fluorescent guanine nucleotide analogues (mant-GDP and mant-GTP). Substitution of either T192 and/or T193 for alanine modestly reduced binding to GDP and significantly reduced the binding affinity for GTP. Furthermore, the T193A mutant protein was more severely impaired for binding GTP than the T192A mutant. The T193A mutation appeared to account solely for the impaired GTP binding of the T192AT193A double mutation. This is the first report that demonstrates that a confirmed defect in guanine nucleotide binding and GTP hydrolysis of an Obg-like protein results in the lack of function in vivo.

Alanine↗
PubMed1998

A mutant of Mycobacterium smegmatis defective in dipeptide transport.

A mutant of Mycobacterium smegmatis unable to use the dipeptide carnosine (beta-alanyl-L-histidine) as a sole carbon or nitrogen source was isolated. Carnosinase activity and the ability to grow on beta-Ala and/or L-His were similar in the mutant and the wild type. However, the mutant showed significant impairment in the uptake of carnosine. This study is the first description of a peptide utilization mutant of a mycobacterium.

Biological Transport↗
PubMed1997

Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway.

A mechanism by which members of the ciliary neurotrophic factor (CNTF)-leukemia inhibitory factor cytokine family regulate gliogenesis in the developing mammalian central nervous system was characterized. Activation of the CNTF receptor promoted differentiation of cerebral cortical precursor cells into astrocytes and inhibited differentiation of cortical precursors along a neuronal lineage. Although CNTF stimulated both the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and Ras-mitogen-activated protein kinase signaling pathways in cortical precursor cells, the JAK-STAT signaling pathway selectively enhanced differentiation of these precursors along a glial lineage. These findings suggest that cytokine activation of the JAK-STAT signaling pathway may be a mechanism by which cell fate is controlled during mammalian development.

Animals↗
PubMed1997

Identification of an essential Caulobacter crescentus gene encoding a member of the Obg family of GTP-binding proteins.

We have identified an essential Caulobacter crescentus gene (cgtA) that encodes a member of a recently identified subfamily of GTPases (the Obg family) conserved from Bacteria to Archaea to humans. This evolutionary conservation between distantly related species suggests that this family of GTP-binding proteins possesses a fundamental, yet unknown, cellular role. In this report, we describe the isolation and sequence of the cgtA gene. The predicted CgtA protein displays striking similarity to the Obg family of small, monomeric GTP-binding proteins, both in the conserved guanine nucleotide-binding domains and throughout the N-terminal glycine-rich domain that is found in many members of the Obg family. Disruption of the cgtA gene was lethal, demonstrating that this gene is essential for cell growth. Immunoblot analysis revealed that CgtA protein levels remained constant throughout the C. crescentus cell cycle.

Alleles↗
PubMed1997

Safety pharmacology of a combination of tinidazole and oxyphenonium bromide.

The effect of a combination of 150 mg tinidazole (CAS 19387-91-8) and 1 mg oxyphenonium bromide (CAS 50-10-2), referred to as the combination, was examined in various animal species to assess its safety. In mice and rats, the combination in the dose range 30-1000 mg/kg p.o. or 250 mg/kg i.p. did not produce behavioural or neurological changes, nor did it influence pentobarbital sleeping time, though, alcohol sleeping time was altered. In anaesthetised dogs, neither blood pressure, ECG, heart rate, respiration or gastrointestinal motility was affected after single intraduodenal administration of the combination 20 and 50 mg/kg or after chronic oral administration of 25 mg/kg daily for 15 days. In isolated organs, viz. perfused rabbit heart, guinea-pig ileum and rat ileum no significant changes were observed following various doses of the combination, compared to tinidazole and oxyphenonium bromide given alone in corresponding concentrations. In conclusion, the pharmacological profile of the aforementioned combination in the dosages employed in mice, rats, guinea-pigs, rabbits and dogs shows that it is safe and well tolerated.

Animals↗
PubMed1995

Identification of a Drosophila G protein alpha subunit (dGq alpha-3) expressed in chemosensory cells and central neurons.

We have identified another Drosophila GTP-binding protein (G protein) alpha subunit, dGq alpha-3. Transcripts encoding dGq alpha-3 are derived from alternative splicing of the dGq alpha locus previously shown to encode two visual-system-specific transcripts [Lee, Y.-J., Dobbs, M.B., Verardi, M.L. & Hyde, D.R. (1990) Neuron 5, 889-898]. Immunolocalization studies using dGq alpha-3 isoform-specific antibodies and LacZ fusion genes show that dGq alpha-3 is expressed in chemosensory cells of the olfactory and taste structures, including a subset of olfactory and gustatory neurons, and in cells of the central nervous system, including neurons in the lamina ganglionaris. These data are consistent with a variety of roles for dGq alpha-3, including mediating a subset of olfactory and gustatory responses in Drosophila, and supports the idea that some chemosensory responses use G protein-coupled receptors and the second messenger inositol 1,4,5-trisphosphate.

Amino Acid Sequence↗
PubMed1994

Image analysis of lateral velopharyngeal closure in repaired cleft palates and normal palates.

We have undertaken the design and testing of a system for making measurements of velopharyngeal function from lateral videofluoroscopic images based upon standard equipment found in any cleft clinic. The uncertainties in the measurements have been found to be acceptably low and, in conjunction with other measurement techniques, the system has made a valuable contribution to the assessment of velopharyngeal function. Additional measurements using this system are presently being developed.

Cleft Lip↗
PubMed1992

Survival of heart failure patients with preserved versus impaired systolic function: the prognostic implication of blood pressure.

The impact of impaired versus preserved systolic function on survival of patients with heart failure was investigated in 78 patients with decompensated heart failure. Patients were classified on the basis of their left ventricular systolic performance, as defined by fractional shortening (FS); group I (n = 56) had impaired systolic function (FS less than 24%) and group II (n = 22) had preserved systolic function (FS greater than or equal to 24%). Mean ejection fraction was 15 +/- 5% and 40 +/- 13% for these groups, respectively. By the end of 48 months, 36 patients in group I had died compared with only 22 patients in group II (p less than 0.05). Both systolic and diastolic blood pressure were significantly lower in the deceased patients compared with the survivors in group I (p less than 0.05). There was a trend for an opposite direction in the relationship of blood pressure to mortality in group II. We conclude that the prognosis of patients with heart failure and preserved systolic function is more favorable than that of those with impaired function, and that blood pressure may have a differential prognostic meaning in the two groups.

Blood Pressure↗
PubMed1989

Transcultural patterns of somatization in primary care: a preliminary report.

The ethnic origins of patients consulting their general practitioners (GP) were determined using criteria of country of birth, religion and preferred language. Three samples with preferred languages of English, Gujarati or Urdu were compared on a standardized interview with regard to symptom complaint, perception and attribution and also completed the General Health Questionnaire and Illness Behaviour Questionnaire. Their GPs provided diagnoses and ratings of physical and mental disorders. Compared with the English group, the Gujaratis had fewer psychosocial complaints, perceived less anxiety and were more likely to attribute their complaints to physical causes. They had higher scores on the Hypochondriasis and Denial scales. Their GPs rated them as less likely to have relevant physical or mental disorders. The Urdu group was intermediate in most respects. Thus somatization was commoner in these two Asian groups with different ethnic origins. However, overall levels of somatization appear to be high even in the English group. No significant differences were found between groups for complaints or ratings of depression, and the differences found in the somatization process appear to be related only to anxiety.

Adolescent↗
PubMed1988

Effect of hexacarbons on selected lipids in developing rat brain and peripheral nerves.

The effects of neurotoxic solvents, i.e. 2,5-hexanedione (2,5-HD), 2,5-hexanediol (2,5-HDiol) and the non-neurotoxic solvent, 2,4-hexanedione (2,4-HD) (500 mg/kg body wt./day, i.p.), have been studied on the lipid composition of brain and sciatic nerves in weanling rats. Five-day-old rats were administered a solvent daily for 21 days. Clinical signs of peripheral neuropathy appeared in 2,5-HD and 2,5-HDiol treated groups. Absolute weights of brain, spleen, thymus significantly decreased with 2,5-HD. Cholesterol content in whole brain homogenates and myelin was significantly reduced with 2,5-HD and 2,5-HDiol treatment. There was also a significant reduction in ubiquinone content of brain with 2,5-HD and 2,5-HDiol treatment. On exposure to neurotoxic chemicals to weanling rats, significant alteration in lipid profile was observed in the brain, which may be one of the key factors in the development of neuropathy.

Animals↗
PubMed1988

Pattern of psychiatric morbidity and alcohol dependence in patients with alcoholic liver disease.

Fifty-six male patients with alcoholic liver disease were evaluated for the presence and severity of alcohol dependence and psychiatric illness using a severity of alcohol dependence questionnaire and research diagnostic criteria, respectively. Forty-three (76.7%) patients were found to be dependent; 26 (46.4%) moderately, and 17 (30.3%) severely. Patients with alcoholic hepatitis were significantly (P less than 0.05) more often found to be dependent than patients with alcoholic cirrhosis. Psychiatric morbidity was observed in 42 (75%) of the patients with alcoholic liver disease and 15 (26.7%) of the nonalcoholic cirrhotics. The difference was highly significant (P less than 0.01). The commonest disorders in patients with alcoholic liver disease were neuroses (33.0%), followed by affective disorders (26.8%). It was, however, not possible to ascertain whether psychiatric disorders antedated alcoholism or were secondary to it. Detection of moderate to severe dependence on alcohol and psychiatric morbidity in about three-fourths of the patients with alcoholic liver disease warrants an increased awareness and a multidisciplinary approach for the management of these patients.

Adult↗
PubMed1988

Ethylenediaminetetra(methylenephosphonic acid): genotoxicity, biodistribution, and subchronic and chronic toxicity in rats.

Ethylenediaminetetra(methylenephosphonic acid), EDITEMPA, was tested for oral toxicity in rats in a 13-wk feeding study (at doses of 0, 5, 50 and 500 mg/kg/day) and in a chronic feeding study (at doses of 0, 4, 20 and 100 mg/kg/day). EDITEMPA was also tested for genotoxicity in the Ames, mouse lymphoma, unscheduled DNA synthesis, and in vivo cytogenetics assays. Additionally, absorption, distribution and excretion (ADE) studies were conducted following administration of [14C]EDITEMPA to rats by gavage and via the feed and drinking-water. The principal finding in the 13-wk study was mild anaemia in male and female rats given 500 mg/kg/day, which was resolved during a 9-wk recovery period. In the chronic study, there was no substantial evidence of any treatment-related toxicity or carcinogenicity. Differences in survival of control and treated females (noted late in the study) were interpreted to represent unusually good survival in controls; however, a compound-related increase in mortality could not be completely ruled out. Tests for genotoxicity were all negative. ADE studies revealed that [14C]EDITEMPA was poorly absorbed from the gastro-intestinal tract and that most of the absorbed dose was rapidly excreted by the kidneys or sequestered in bone. The gavage route of administration led to four- to six-fold increases in bone EDITEMPA levels as compared with administration in the feed and drinking-water, respectively. These results suggest that no significant toxicity or carcinogenicity concerns arise from EDITEMPA when it is administered in the feed at the concentrations tested. Reversible anaemia was seen only at very high doses and was interpreted as being secondary to EDITEMPA's ability to interfere with iron absorption and utilization. Localization of EDITEMPA in bone indicated a high degree of affinity for mineralizing tissues, consistent with its chelating properties. There was, however, no effect on bone resorption or mineralization. A comparison of human drinking-water levels of 3500 ppm EDITEMPA (based on a no-effect level of 100 mg/kg/day in rats) with the estimated worst-case exposure in humans of 0.01 ppm suggested a safety margin greater than 1 x 10(5).

Administration, Oral↗