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Biomedical subjects

A Singh

Publications and source records attributed to A Singh.

At least 451 records · Page 25Linked to original sources
PubMed1993

Familial interruption of the aortic arch.

Interruption of the aortic arch (IAA) is an important congenital cardiac malformation occurring in 1.4% of cases with a congenital cardiac malformation. Only two reports have described IAA in siblings, each with type B and an anomalous right subclavian artery. We report the occurrence of IAA type B with an anomalous right subclavian artery in two siblings and their half-sibling, each of whom had additional conotruncal cardiac malformations. Recent evidence suggests that conotruncal cardiac malformations, including IAA type B, are related to abnormalities of neural crest cell migration. Thus, the family reported herein may manifest a syndrome related to alterations in mesenchymal tissue/neural crest cell migration.

Aorta, Thoracic↗
PubMed1993

Antidepressant-like activity of compounds with varying efficacy at 5-HT1A receptors.

Three novel compounds (WY-48,723, WY-50,324, WY-47,846 [zalospirone]), with high affinity but varying efficacy for the 5-HT1A receptor, were examined for producing the 5-HT behavioral syndrome and for potential antidepressant activity in the forced swimming test (FST). WY-50,324 was more potent than WY-48,723 at producing the 5-HT syndrome, but unlike WY-48,723, it produced only some of the behaviors of the 5-HT syndrome and its profile resembles that of a partial agonist. WY-48,723 appeared to be a full agonist because it produced behavioral effects similar to those of 8-OH-DPAT. The syndrome produced by these compounds was antagonized by pretreatment with pindolol. Zalospirone did not produce the syndrome but it antagonized the syndrome produced by 8-OH-DPAT. WY-48,723 and WY-50,324 reduced immobility time in the FST. These effects were similar to those produced by the tricyclic antidepressant desipramine and the 5-HT1A agonist 8-OH-DPAT. Zalospirone did not reduce immobility time, but increased it, which made it difficult to evaluate in this screen. These results suggest that the full agonist WY-48,723 and the partial agonist WY-50,324 may both possess antidepressant activity. Antidepressant-like activity appears to be a characteristic of compounds with a medium to high efficacy for activating 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Modulatory effect of Areca nut on the action of mace (Myristica fragrans, Houtt) on the hepatic detoxification system in mice.

The present paper reports the modifying potential of areca nut (Areca catechu), an ingredient of the habitual masticatory betel quid, on the induction of the hepatic detoxification system in mice by mace (the aril of nutmeg, Myristica fragrans) a known chemopreventor of chemically induced carcinogenesis. The modulatory effect of areca nut was assessed by determining the levels of enzymes of the hepatic detoxification system, such as glutathione S-transferase (GST), cytochrome b5 and cytochrome P-450, and the content of acid-soluble sulphhydryl (-SH). Mice were fed either control diet or diet containing 0.25, 0.5 or 1% areca nut for 45 days. During the last 10 days the diet was supplemented with 0.5 or 1% mace. At 0.5 and 1% in the diet, areca nut decreased mace-induced increases in hepatic GST and -SH levels and elevated further increases in the levels of cytochrome b5 and cytochrome P-450.

Animals↗
PubMed1993

Hexachlorobenzene toxicity in the monkey primordial germ cell without induced porphyria.

Hexachlorobenzene is a persistent chlorinated organic chemical that has been detected in many tissues from a variety of species including human ovary and human ovarian follicular fluid. When administered in high dosage to nonhuman primates, hexachlorobenzene causes destruction of ovarian primordial germ cells in association with systemic toxicity. The purpose of these experiments was to assess relative ovarian germ cell sensitivity at much lower dosages of hexachlorobenzene that do not produce systemic effects and additionally to evaluate oocyte function by means of the response to superovulation, fertilization, and embryo cleavage during a cycle of in vitro fertilization in the cynomolgus monkey. Hexachlorobenzene in dosages of 0.1, 1.0, and 10.0 mg/kg/day was administered orally by gelatin capsule for 90 days. There was a dose-dependent accumulation of HCB in serum and other tissues without any change in the serum estradiol response to human menopausal gonadotropin, oocyte recovery, oocyte maturation, oocyte fertilization in vitro, and early embryo cleavage rate. There was a dose-related toxic effect observed in primordial germ cells at the lowest dose despite no evidence of systemic or hepatic effects. As there were no changes in the urinary porphyrin excretion, the mechanism of hexachlorobenzene ovotoxicity may be distinct from hexachlorobenzene-induced cytochrome P-450-dependent inhibition of uroporphobilinogen decarboxylase in the liver, although such intraovarian metabolism cannot be excluded.

Animals↗
PubMed1993

The role of free fatty acids in regulating the tissue availability and synthesis of sex steroids.

Sex steroids and dietary fat intake have been implicated in the growth of breast tumours. We have previously shown that the plasma free oestradiol fraction is increased in women with breast cancer and that the addition of free fatty acids (FFA) to plasma can increase the free oestradiol fraction in vitro. In the present study we have examined the distribution of oestradiol and testosterone in serum obtained from European women (EW) and Asian (Gujarati) women (GW) living in north-west London. Fat intake by these women is similar but GW, who are vegetarians, consume a greater proportion of unsaturated fats. In serum from perimenopausal GW, the free testosterone concentration was significantly higher than for EW (11.1 +/- 3.6 pmol/l vs 8.7 +/- 3.4 pmol/l, p < 0.05). Although a significant correlation was found between the free testosterone and FFA concentrations for GW (r = 0.49, p < 0.05), concentrations of sex-hormone binding globulin (SHBG) were significantly lower in GW than EW. The finding of lower SHBG concentration in GW was confirmed in a second study in postmenopausal women (EW, 60.1 +/- 34.1 nmol/l; GW, 37.8 +/- 20.5 nmol/l, p < 0.05). However, no difference in the free oestradiol fraction or concentration was detected for EW and GW and no correlations with total or individual FFA were found. It is concluded from this study that while dietary fats may have an important role in the development of breast tumours, it is unlikely to be mediated by FFA inhibiting the binding of sex steroids to plasma proteins.

Adult↗
PubMed1993

Effect of anterior capsulotomy on decentration of a two-zone multifocal intraocular lens.

A study was undertaken to determine if can-opener (CO) or continuous curvilinear capsulorhexis (CCC) anterior lens capsulotomy influences decentration of a two-zone multifocal intraocular lens (IOL). Fifty IOLs (25 with polypropylene haptics and 25 with poly[methyl methacrylate] haptics) were implanted following CO, 42 with poly(methyl methacrylate) haptics, following CCC. The extent and direction of decentration was estimated using a photogeometric technique. The haptic material may influence decentration. Continuous curvilinear capsulorhexis was associated with less decentration than CO (0.36 mm and 0.43 mm, respectively). The difference, however, was not statistically significant.

Adult↗
PubMed1993

Responses of plasma magnesium and other cations to fluid replacement during exercise.

Changes in plasma magnesium (Mg) and other cations in response to exercise have been previously reported, but whether ingestion of fluids providing carbohydrate and electrolytes modifies the changes has not been determined. We examined patterns of change in plasma Mg, calcium (Ca), sodium (Na), and potassium (K) in 10 men [age 30 +/- 2 years; maximal oxygen uptake (VO2max) 57.4 +/- 3.2 ml.kg-1.min-1] who ran on a treadmill for 2 hours at 60-65% of their VO2max. Subjects drank 200 mL of water (W) or a 7% glucose polymer/fructose/electrolyte solution (GPFE) at 0 time and every 30 minutes while running (30, 60 and 90 minutes). Plasma Mg continued to decline throughout exercise and was lowest when exercise was terminated at 120 minutes (87.9 +/- 1.2 and 88.9 +/- 2.2% of pre-exercise for W and GPFE, respectively). In contrast, a significant increase in serum K was noted (105.2 +/- 3.6 and 112.8 +/- 3.0% of pre-exercise at time 120 for W and GPFE). Serum Na increased slightly, but no changes in plasma Ca were observed. Serum glucose and lactate increased transiently for all running conditions, but no differences across fluid treatments were noted. Serum free fatty acids (FFA) increased during exercise with W ingestion, whereas no rise in serum FFA occurred with GPFE until the end of exercise. That patterns of change in Mg and K during exercise were not altered by providing a fluid replacement beverage containing glucose polymer, fructose, Mg, K, Ca, and Na, as compared to water, suggests that these events may be requisite to maintenance of homeostasis. Mechanisms must be sought to explain the decline in plasma Mg that occurs with exercise.

Adult↗
PubMed1993

Thy-1 antibody-triggered neurite outgrowth requires an influx of calcium into neurons via N- and L-type calcium channels.

We present evidence that the neurite out-growth stimulated by the binding of Thy-1 antibodies to PC12 cells is mediated by calcium influx through both N- and L-type calcium channels. PC12 cells cultured on a noncellular substratum in the presence of NGF, or on a cellular substratum in the absence of NGF, responded to soluble Thy-1 antibody by extending longer neurites. The response required bivalent antibody and could be blocked by removing Thy-1 from the surface of PC12 cells with phosphatidylinositol specific phospholipase C. The response could also be blocked by reducing extracellular calcium to 0.25 mM, or by antagonists of L- and N-type calcium channels. Additionally, the response could be fully inhibited by preloading PC12 cells with BAPTA/AM which buffers changes in intracellular calcium. A heterotrimeric G-protein is also implicated in the pathway as the response could be fully inhibited by pertussis toxin. These data suggest that antibody-induced clustering of Thy-1 stimulates neurite outgrowth by activating a second messenger pathway that has previously been shown to underlie cell adhesion molecule (NCAM, N-cadherin, and L1), but not integrin or NGF-dependent neurite outgrowth.

3T3 Cells↗
PubMed1993

Improvement of structure and function in orthotopic small bowel transplantation in the rat by glutamine.

Significant atrophy and impaired absorption occur in the heterotopically transplanted small intestinal isograft, and these deficits are corrected when the preferred fuel of the enterocyte, glutamine (Gln), is supplemented to total parenteral nutrition (TPN). In the orthotopic small bowel isograft, this study determined whether Gln-enriched TPN enhanced mucosal structure and function, and decreased bacterial translocation to mesenteric lymph nodes (MLN). Seventeen adult Lewis rats received orthotopic jejunal isografts and central venous catheters for TPN. Rats received either TPN with 2% Gln or the same TPN with isonitrogenous balanced nonessential amino acids for 10 days. Eight normal, chow-fed rats served as baseline controls. Mucosal villous height, surface area, crypt depth, weight, protein and DNA contents, brush border enzymes, 14C glucose absorption, and bacterial translocation to MLN were evaluated in both the graft and host jejunum and the control animals. Gln-enriched TPN significantly increased mucosal villous height (P < 0.01), surface area (P < 0.01), and glucose absorption (P < 0.01), and it reduced bacterial translocation (P < 0.05) when compared with the non-Gln TPN group. For most study variables, there were no significant differences between Gln-enriched TPN or baseline and between the graft and host jejunum for Gln- and non-Gln-supplemented animals. There were no significant differences in DNA content and brush border enzymes among groups. These results indicate that Gln-enriched TPN improves mucosal structure and glucose absorption and reduces bacterial translocation to MLN in the orthotopic small bowel isograft.

Animals↗
PubMed1993

Radiofrequency catheter ablation of idiopathic left ventricular tachycardia guided by a Purkinje potential.

BACKGROUND: Verapamil-sensitive, idiopathic left ventricular tachycardia (ILVT) with right bundle branch block configuration and left-axis deviation has been suggested to originate from the left posterior fascicle. The purpose of this study was to determine how frequently potentials generated by the Purkinje fiber network (P potential) can be recorded preceding ventricular activation, and the role of the P potential in guiding radiofrequency catheter ablation. METHODS AND RESULTS: Eight patients (mean age, 26 +/- 10 years) with ILVT (cycle length, 346 +/- 59 milliseconds) were studied. Right and left ventricular endocardial mapping during tachycardia identified earliest ventricular activation at the posteroapical left ventricular septum. In all patients, earliest ventricular activation during tachycardia was preceded by a distinct potential. This potential also preceded ventricular activation during sinus rhythm, consistent with activation of a segment of the left posterior fascicle (P potential). The earliest recorded P potential preceded the QRS during tachycardia by 15 to 42 milliseconds (mean, 27 +/- 9 milliseconds). The application of radiofrequency current at 1 to 4 sites (median, 1) eliminated ILVT in all eight patients. In the seven patients with P potentials recorded at multiple sites within the posteroapical septum, ablation was successful at the site of the earliest P potential and unrelated to the timing of ventricular activation. In the remaining patient, ablation was successful at a site recording a late P potential fusing with earliest ventricular activation. During follow-up (1 to 67 months; median, 10.5) ILVT recurred only in the latter patient. Pace mapping during tachycardia at the successful ablation site in four patients produced a similar QRS with stimulus-QRS interval equal to P-QRS interval during tachycardia. However, a similar QRS was obtained by pacing at nearby sites that recorded a later P potential. CONCLUSIONS: These findings support the hypothesis that ILVT originates from the Purkinje network of the left posterior fascicle. A P potential can be recorded at the posteroapical left ventricular septum during ILVT, and ablation is successful at the site recording the earliest P potential. Pace mapping with similar QRS is not specific due to capture of the Purkinje fiber network at a site remote from the origin of the tachycardia.

Adolescent↗
PubMed1993

Increased plasma viscosity as a reason for inappropriate erythropoietin formation.

The aim of this study was to examine whether altered plasma viscosity could contribute to the inappropriately low production rate of erythropoietin (EPO) observed in patients suffering from hypergammaglobulinemias associated with multiple myeloma or Waldenström's disease. We found that the EPO formation in response to anemia in these patients was inversely related to plasma viscosity. A similar inverse relationship between plasma viscosity and EPO production was seen in rats in which EPO formation had been stimulated by exchange transfusion and the plasma viscosity of which was thereby altered by using exchange solutions of different composition to alter plasma viscosity and thus whole blood viscosity independently from hematocrit. Raising the gammaglobulin concentration to approximately 40 mg/ml plasma in the rats almost totally blunted the rise in serum EPO levels despite a fall of the hematocrit to 20%. Determination of renal EPO mRNA levels by RNase protection revealed that the reductions in serum EPO levels at higher plasma viscosities were paralleled by reductions in renal EPO mRNA levels. Taken together, our findings suggest that plasma viscosity may be a significant inhibitory modulator of anemia-induced EPO formation. The increased plasma viscosity in patients with hypergammaglobulinemias may therefore contribute to the inappropriate EPO production, which is a major reason for the anemia developing in these patients.

Adult↗
PubMed1993

Individual variation in the composition of colostrum and absorption of colostral antibodies by the precolostral buffalo calf.

The total protein and Ig content in the first colostrum was higher in buffalo cows than in dairy crossbred cows. Individual variation in Ig content of first colostrum may be responsible for differences in susceptibility of calves to infections. The decline in Ig content during subsequent milkings was faster in dairy crossbred cows. The major class was IgG in both species. Absorption of colostral proteins and Ig was 14.0 g (68%) and 4.6 g (75.4%), respectively, within 1 h of feeding colostrum to a 7-h-old female buffalo calf. Absorption was decreased to 2.1 and .83 g/h after the first feeding, suggesting that the intestinal absorption of macromolecules declined 1 h after the first feeding. Marginal placental transfer of maternal Ig also was demonstrated in buffalo. An albuminlike protein was predominant in blood plasma of the precolostral buffalo calf. This protein decreased, and IgG in blood plasma increased, after colostrum was fed, indicating that albuminlike protein may be involved in the transfer of maternal nutrients to the fetus.

Absorption↗
PubMed1993

Steroid withdrawal, rejection and the mixed lymphocyte reaction in children after renal transplantation.

With improved long-term graft survival after renal transplantation, cardiovascular mortality is emerging as the leading cause of death in adults and is also being reported in children. Chronic corticosteroid therapy is thought to be an important cause of post-transplant hyperlipidemia and hypertension. This study describes a steroid withdrawal protocol initiated to reduced cardiovascular risk factors in pediatric renal allograft recipients, reports on the rate of rejection observed and the use of an in vitro method to measure immunoresponsiveness and identify those patients who have not experienced a rejection episode. Thirty-six of 67 patients were able to discontinue prednisone and were maintained on cyclosporine alone. Twenty-two of the 36 patients experienced an acute rejection episode a mean of 14 months (range 1.5 to 36 months) after completion of the steroid taper. Ten of the 22 rejections occurred within 12 months after completion of the taper. Fourteen patients remain rejection free to date for a mean of 70.3 months (range 19 to 111 months) after withdrawal. Using the mixed lymphocyte culture reaction, we tested the hypothesis that steroid dependent recipients (SDR) will express donor antigen specific responsiveness and steroid independent recipients (SIR) will exhibit donor antigen-specific tolerance. Four of seven SDR were tolerant to donor specific antigens but responsive to unrelated controls, while five of six SIR were responsive to donor specific antigens. These unanticipated results highlight the complexity of allograft tolerance.

Child, Preschool↗