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Biomedical subjects

A Tandon

Publications and source records attributed to A Tandon.

At least 37 records · Page 2Linked to original sources

Cognitive abilities of asphyxiated survivors beyond 5 years of age.

OBJECTIVE: To evaluate the intellectual, psychoeducational and social maturity of a cohort of unimpaired asphyxiated survivors beyond 5 years of age. DESIGN: Case control study on hospital based cohorts on a longitudinal follow up at High Risk and Well Baby Clinics of a teaching hospital. METHODS: The demographic data of these children was recorded. A detailed physical examination was performed. The tests of cognition included the Stanford Binet and the Raven's Progressive matrices. Academic achievement was evaluated by the Wide range achievement test-Revised (WRAT-R). Assessment of visuo-motor integration was done by the Bender Gestalt Test. The proportion of children having soft neurological signs was determined. Vineland Social Maturity Scale was performed on all children. RESULTS: Fifty-four asphyxiated and 57 matched control children participated in the study. Of the 54 asphyxiated children, 27 were tested at a mean age of 7.2 +/- 1.6 years (Group 1) and 27 were tested at a mean age of 10.9 +/- 1.52 years (Group 2). The asphyxiated children as a group performed in the normal range on tests of cognition and academic achievement but were significantly disadvantaged (p < 0.005) as compared to controls. A higher percentage of asphyxiated children had low scores on the Bender Gestalt Test as compared to controls but the difference was not significant. A significantly higher proportion of asphyxiated children of both the groups showed the presence of soft neurological signs as compared to controls. Approximately 11% of the asphyxiated children performed in the abnormal range in the Vineland Social Maturity Scale. CONCLUSION: Cognitive abilities of asphyxiated children beyond the age of 5 years are impaired in comparison to controls, emphasizing the need for early detection and referral for special education.

Adolescent↗

Effect of lithium on hepatic drug-metabolizing enzymes of protein-deficient rats.

Protein deficiency was produced by feeding synthetic 8%-protein diet. Lithium carbonate at the dose level of 1.1g/kg diet was administered to normal and protein-deficient rats for a period of one mo. A significant inhibition in the levels of cytochrome (cyt) P450, cyt b5, glutathione (GSH), glutathione S-transferase (GST) and glutathione peroxidase (GPx), but an increase in gamma-glutamyl transpeptidase (gamma-GT), was observed in low-protein LP-fed rats. Lithium treatment to normal rats caused no significant change in the activities of cyt P450, cyt b5, GST, and GSH levels, whereas there was elevation in the activities of gamma-GT and GPx and suppression in glutathione reductase (GRd) activity. Lithium administration to LP-fed rats resulted in significant increases in the hepatic gamma-GT and GPx activities.

Animals↗

Structure and mutational analysis of Rab GDP-dissociation inhibitor.

The crystal structure of the bovine alpha-isoform of Rab GDP-dissociation inhibitor (GDI), which functions in vesicle-membrane transport to recycle and regulate Rab GTPases, has been determined to a resolution of 1.81 A. GDI is constructed of two main structural units, a large complex multisheet domain I and a smaller alpha-helical domain II. The structural organization of domain I is surprisingly closely related to FAD-containing monooxygenases and oxidases. Sequence-conserved regions common to GDI and the choroideraemia gene product, which delivers Rab to catalytic subunits of Rab geranylgeranyltransferase II, are clustered on one face of the molecule. The two most sequence-conserved regions, which form a compact structure at the apex of GDI, are shown by site-directed mutagenesis to play a critical role in the binding of Rab proteins.

Adaptor Proteins, Signal Transducing↗

Fulminant hepatitis in a tropical population: clinical course, cause, and early predictors of outcome.

The profiles of patients with fulminant hepatic failure (FHF) from developing countries have not been reported earlier. The current study was conducted prospectively, at a single tertiary care center in India, to document the demographic and clinical characteristics, natural course, and causative profile of patients with FHF as well as to define simple prognostic markers in these patients. Four hundred twenty-three consecutive patients with FHF admitted from January 1987 to June 1993 were included in the study. Each patient's serum was tested for various hepatotropic viruses. Univariate Cox's regression for 28 variables, multivariate Cox's proportional hazard regression, stepwise logistic regression, and Kaplan-Meier survival analysis were done to identify independent predictors of outcome at admission. All patients presented with encephalopathy within 4 weeks of onset of symptoms. Hepatotropic viruses were the likely cause in most of these patients. Hepatitis A (HAV), hepatitis B (HBV), hepatitis D (HDV) viruses, and antitubercular drugs could be implicated as the cause of FHF in 1.7% (n= 7), 28% (n= 117), 3.8% (n= 16), and 4.5% (n= 19) patients, respectively. In the remaining 62% (n= 264) of patients the serological evidence of HAV, HBV, or HDV infection was lacking, and none of them had ingested hepatotoxins. FHF was presumed to be caused by non-A, non-B virus(es) infection. Sera of 50 patients from the latter group were tested for hepatitis E virus (HEV) RNA and HCV RNA. In 31 (62%), HEV could be implicated as the causative agent, and isolated HCV RNA could be detected in 7 (19%). Two hundred eighty eight (66%) patients died. Approximately 75% of those who died did so within 72 hours of hospitalisation. One quarter of the female patients with FHF were pregnant. Mortality among pregnant females, nonpregnant females, and male patients with FHF was similar (P > .1). Univariate analysis showed that age, size of the liver assessed by percussion, grade of coma, presence of clinical features of cerebral edema, presence of infection, serum bilirubin, and prothrombin time prolongation over controls at admission were related to survival (P < .01). The rapidity of onset of encephalopathy and cause of FHF did not influence the outcome. Cox's proportional hazard regression showed age > or = 40 years, presence of cerebral edema, serum bilirubin > or = 15 mg/dL, and prothrombin time prolongation of 25 seconds or more over controls were independent predictors of outcome. Ninety-three percent of the patients with three or more of the above prognostic markers died. The sensitivity, specificity, positive predictive value, and the negative predictive value of the presence of three or more of these prognostic factors for mortality was 93%, 80%, 86%, and 89.5%, respectively, with a diagnostic accuracy of 87.3%. We conclude that most of our patients with FHF might have been caused by hepatotropic viral infection, and non-A, non-B virus(es) seems to be the dominant hepatotropic viral infection among these patients. They presented with encephalopathy within 4 weeks of the onset of symptoms. Pregnancy, cause, and rapidity of onset of encephalopathy did not influence survival. The prognostic model developed in the current study is simple and can be performed at admission.

Adolescent↗

Effects of colchicine application to preganglionic axons on choline acetyltransferase activity and acetylcholine content and release in the superior cervical ganglion.

These experiments investigate the effect of block, by colchicine, of fast axonal transport in the cat's cervical sympathetic trunk (CST) on the superior cervical ganglion's choline acetyltransferase (ChAT) enzyme activity, acetylcholine (ACh) content, and ACh release. Electron microscopy on the segment of the CST exposed to colchicine 1 or 4 days earlier showed disappearance of microtubules and accumulation of vesicles and smooth membrane tubules but no disruption of the axonal cytomatrix. At 4 days following colchicine treatment, the number and size of synaptic boutons per grid square in the ganglion ipsilateral to the colchicine-treated CST were similar to those in the control ganglion. At 2 and 4 days following exposure of the CST to colchicine, ChAT activity in the ipsilateral ganglion was reduced to 78 +/- 8 and 54 +/- 8% of control values, respectively. ACh stores in the ganglia were also reduced (to 81 +/- 6% of control values at 2 days and to 51 +/- 5% of control values at 4 days). Ganglionic transmission and its sensitivity to blockade by hexamethonium during 2-Hz CST stimulation were not impaired at day 4 postcolchicine. ACh release evoked by 2-Hz stimulation of colchicine-treated axons was similar to release from untreated axons, despite the decrease in the ganglionic ACh content. In contrast, ACh release evoked by 20-Hz stimulation was depressed. The amount of ACh released during 5-Hz stimulation in the presence of vesamicol by the terminals of colchicine-treated axons was similar to that released by the terminals of untreated axons. These results suggest the following conclusions: (a) Colchicine-sensitive fast axonal transport contributes significantly to maintaining ChAT stores in preganglionic axon terminals. (b) The half-life of ChAT in sympathetic preganglionic terminals is approximately 4 days. (c) One consequence of colchicine-induced block of axonal transport is a reduced ACh content of preganglionic nerve terminals. (d) This decrease in ACh content appears to be the result of a loss in a reserve transmitter pool, whereas the size of the readily releasable compartment is maintained.

Acetylcholine↗

Epidemiology of hepatitis B virus infection in India.

The average estimated carrier rate of hepatitis B virus (HBV) in India is 4%, with a total pool of approximately 36 million carriers. Wide variations in social, economic, and health factors in different regions may explain variations in carrier rates from one part of the country to another. Professional blood donors constitute the major high risk group for HBV infection in India, with a hepatitis B surface antigen positivity rate of 14%. Blood transfusions represent the most important route of HBV transmission among adults. However, most of India's carrier pool is established in early childhood, predominantly by horizontal spread due to crowded living conditions and poor hygiene. Acute and subacute liver failure are common complications of viral hepatitis in India and HBV is reckoned to be the aetiological agent in 42% and 45% of adult cases, respectively. HBV is reported to be responsible for 70% of cases of chronic hepatitis and 80% of cases of cirrhosis of the liver. About 60% of patients with hepatocellular carcinoma are HBV marker positive. Small numbers of patients have been reported to be infected with the pre-core mutant virus but none with the S mutant. Coinfection with hepatitis C virus or hepatitis delta virus is comparatively uncommon. In conclusion, hepatitis B is a major public health problem in India and will continue to be until appropriate nationwide vaccination programmes and other control measures are established.

Hepatitis B↗

Increased acetylcholine content induced by antidromic stimulation of a sympathetic ganglion: a possible retrograde action of adenosine.

Prolonged high-frequency orthodromic stimulation of superior cervical ganglia is known to result in increased acetylcholine (ACh) synthesis and ACh content after the period of stimulation. In a previous study, we provided evidence to suggest that adenosine acts as an extracellular signal to activate this increased ACh synthesis and we proposed that the source of that adenosine might be postsynaptic. Thus, the purpose of the present study was to test whether direct stimulation of the post-ganglionic nerves could affect ganglionic ACh content. Antidromic conditioning of ganglia (15 Hz, 45 min) did not affect significantly their ACh content. However, if ganglia were allowed a 15-min rest period after this antidromic conditioning, their ACh stores were increased by 20%; a similar increase was induced by 4-Hz stimulation before the rest period. During the 15-Hz antidromic stimulation, ACh release was not clearly increased above the basal level, suggesting that preganglionic nerve endings were not stimulated to an extent that could explain the increased ACh content. Orthodromic stimulation (5 Hz) of ganglia 15 min after they had been subjected to antidromic conditioning (15 Hz, 45 min) showed increased ACh release in comparison with that from control unconditioned ganglia. Moreover, the extra ACh released by the conditioned ganglia was quantitatively similar to the increase in the ACh stores, as if most, or all, of the additional ACh was released by preganglionic stimulation. If the antidromic conditioning and the rest period were done during perfusion with Ca(2+)-free medium, the ganglia did not accumulate extra ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

p53 and human papilloma virus type 16 in cervical intraepithelial neoplasia and carcinoma.

A series of cervical biopsies and excision specimens representing normal cervical epithelium, metaplastic epithelium, cervical intraepithelial neoplasia and cervical carcinoma were examined for the presence of p53 in relation to the human papillomavirus type 16 (HPV 16). The results show that p53 accumulation in premalignant cervical lesions is almost identical to the low levels detected in normal endo- and ectocervical epithelia, reserve cells, immature and mature squamous metaplastic epithelium. p53 levels were low and seem to be independent of the grade in cervical intraepithelial neoplasia (CIN). However, carcinomas of the cervix contained high levels of immunohistochemically detectable p53. Apparently, a p53 mutation is not an early factor in cervical carcinogenesis. Furthermore, our studies demonstrate that alterations in p53 levels and the presence of HPV 16 are not mutually exclusive markers of cervical tumorigenesis. This contrasts with several reports in the literature and underlines the observation that p53 expression is probably an inadequate prognosticator for estimating progression or regression of CIN lesions.

DNA, Viral↗

An X-ray crystallographic study of the nonsteroidal contraceptive agent centchroman.

We have determined an X-ray crystal structure for the N-methyl iodide derivative of the nonsteroidal contraceptive centchroman. The pendant aromatic substituents on C-3 and C-4 of the chroman system are nearly perpendicular to the plane of the chroman system, an orientation expected in such a chroman, but perturbed to some degree by the gem dimethyl substituents at C-2. Structural superposition with other nonsteroidal antiestrogens, tamoxifen and nafoxidine, shows a similar disposition of the tertiary amine side chains responsible for antagonist activity. The aryl rings also show good superposition, but in contrast to tamoxifen and nafoxidine, which have the potential for ring double bond conjugation, the centchroman aryl rings show a larger dihedral twist. While different superpositions between the enantiomers of centchroman and the bioactive enantiomer of estradiol (d-estradiol, 8 beta,9 alpha,13 beta,14 alpha,17 beta) are possible, when the chroman ring system is positioned over the AB rings of estradiol, then (3R,4R)-centchroman makes the best fit. The aryl substituents in both enantiomers make comparable overlays with the steroidal skeleton, but the axial methyl group at C-2 in (3R,4R)-centchroman is directed downward along the C-7 alpha axis of estradiol, a site where many substituents are known to be well tolerated by the estrogen receptor, while in the 3S,4S-enantiomer, this methyl group is projected upward. Thus, we suggest that the bioactive l-enantiomer of centchroman will have the 3R,4R absolute configuration.

Centchroman↗

The role of endogenous adenosine in a poststimulation increase in the acetylcholine content of a sympathetic ganglion.

Previous experiments showed that exposure of sympathetic ganglia to exogenous adenosine increased acetylcholine (ACh) content and its subsequent release. This effect was not mediated through extracellular adenosine receptors, but at an intracellular site following its uptake through nitrobenzylthioinosine (NBTI)-resistant nucleoside transporters. We postulated that endogenous adenosine may play a role in modulating synaptic transmission in the superior cervical ganglion. The present study tested whether adenosine is involved in the activation of ACh synthesis that occurs during a rest period following prolonged presynaptic tetanic activity. Conditioning of ganglia with high-frequency stimulation (15 Hz) for 45 min followed by a 15 min rest increased their ACh content by 45%. The appearance of this "rebound ACh" showed sensitivity to nucleoside transport inhibitors; it was prevented by dipyridamole, but not by NBTI or meclonazepam, and it was reduced in the presence of RO 11-3624, suggesting an involvement of NBTI-resistant transporters. The effect of dipyridamole was specific for the synthesis of rebound ACh in that it did not inhibit ACh release or ACh synthesis during stimulation. The inhibitory action of dipyridamole on the synthesis of rebound ACh was not evident if it was present only during the tetanic stimulation but it was if dipyridamole was present during the rest period following it, suggesting that adenosine's presence after tetanic stimulation is of importance. This conclusion was strengthened by experiments showing that the presence of cyclopentyltheophylline, an antagonist at inhibitory adenosine receptors, increased ACh output evoked by test stimulation immediately following tetanic activity, as if endogenous adenosine was available at that time to activate the adenosine receptors that inhibit transmitter release. ACh release from conditioned ganglia was 44% greater than that from the controls. However, the rebound ACh was not mobilized in the presence of 2-(4-phenylpiperidino)cyclohexanol (vesamicol), a vesicular ACh transporter inhibitor. These results suggest that endogenous adenosine released after tetanic stimulation activates ACh synthesis, which results in an increase of ganglionic ACh that is available for subsequent mobilization and release.

Acetylcholine↗

Increased acetylcholine content induced by adenosine in a sympathetic ganglion and its subsequent mobilization by electrical stimulation.

The present study was initiated to examine the effects of ATP on acetylcholine (ACh) synthesis. The exposure of superior cervical ganglia to ATP increased ACh stores by 25%, but this effect was also evident with ADP, AMP, and adenosine, but not with beta gamma-methylene ATP, a nonhdydrolyzable analogue of ATP, or with inosine, the deaminated product of adenosine. Thus, we attribute the enhanced ACh content caused by ATP to the presence of adenosine derived from its hydrolysis by 5'-nucleotidase. The adenosine-induced increase of tissue ACh was not the consequence of an adenosine-induced decrease of ACh release. The extra ACh remained in the tissue for more than 15 min after the removal of adenosine, but it was not apparent when ganglia were exposed to adenosine in a Ca(2+)-free medium. Incorporation of radiolabelled choline into [3H]ACh was also enhanced in the presence of adenosine, suggesting an extracellular source of precursor. Moreover, the synthesis of radiolabelled forms of phosphorylcholine and phospholipid was not reduced in adenosine's presence, suggesting that the extra ACh was not likely derived from choline destined for phospholipid synthesis. Aminophylline did not prevent the adenosine effect to increase ACh content; this effect was blocked by dipyridamole, but not by nitrobenzylthioinosine (NBTI). In addition, two benzodiazepine stereoisomers known to inhibit stereoselectively the NBTI-resistant nucleoside transporter displayed a similar stereoselective ability to block the effect of adenosine. Together, these results argue that adenosine is transported through an NBTI-resistant nucleoside transporter to exert an effect on ACh synthesis. The extra ACh accumulated as a result of adenosine's action was releasable during subsequent preganglionic nerve stimulation, but not in the presence of vesamicol, a vesicular ACh transporter inhibitor. We conclude that the mobilization of ACh is enhanced as a result of adenosine pretreatment.

Acetylcholine↗

A preliminary open trial on interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the treatment of subacute hepatic failure.

The efficacy of the interferon stimulator named Stronger Neo Minophagen-C (SNMC) derived form the plant G. glabra was studied at a dose of 40 or 100 ml daily for 30 days followed by thrice weekly intravenously for 8 wk in 18 patients of subacute hepatic failure due to viral hepatitis. The survival rate amongst these patients was 72.2 per cent, as compared to the earlier reported rate of 31.1 per cent in 98 patients who received supportive therapy (P < 0.01). Death in four of the five patients was due to associated infections leading to hepatorenal failure and terminal coma. Further studies are necessary to standardize the dose and duration of therapy with SNMC in subacute hepatic failure.

Adolescent↗