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Biomedical subjects

R Patel

Publications and source records attributed to R Patel.

At least 325 records · Page 18Linked to original sources
PubMed1990

Senile cataract and glucose-6-phosphate dehydrogenase deficiency in Indians.

Erythrocytic glucose-6-phosphate dehydrogenase (G-6-PD) was tested in 163 cases of senile cataract and 79 age- and sex-matched controls. There was no statistically significant difference between the overall incidence of G-6-PD deficiency in cataract in comparison to controls. However, amongst the cataract patients the frequency of G-6-PD deficiency was significantly higher in the age group 40 to 50 years (12.1%) as compared to those aged 51 years or more.

Adult↗
PubMed1990

Gastric emptying and the pharmacokinetics of the cephalosporin antibiotic, cefpodoxime proxetil.

The effects of gastric motility on the pharmacokinetics of cefpodoxime proxetil, an oral, broad spectrum, third-generation cephalosporin antibiotic were evaluated in 12 healthy subjects. In this open-label, crossover trial, each subject took a 200 mg dose (two 100 mg film-coated tablets) in each study period. There was an initial fasting period followed by a control period and then either a propantheline or metoclopramide period. Gastric motility was measured using [99mTc]-labeled sulfur colloid in oatmeal in the control, propantheline and metoclopramide periods. Treatment with propantheline or metoclopramide was given 30 min before dosing with the antibiotic and the radioisotope. Serial images with a gamma counter were made every 15 min for 2 h. Gastric emptying time was faster than control with metoclopramide, but generally slower with propantheline than control. The mean peak plasma concentration, mean area under plasma concentration time curve and mean half-life of cefpodoxime proxetil were similar in all groups as compared to control. The mean time to peak plasma concentration was delayed in the propantheline period and peak plasma concentrations were greater at all sampling times at six hours after dosing. This study utilized the gastric nuclear scan with modification of gastric motility by metoclopramide and propantheline and with simultaneous determination of the disposition of cefpodoxime proxetil to understand the absorption of the drug.

Adolescent↗
PubMed1989

Mutation of the high cysteine region of the human insulin receptor alpha-subunit increases insulin receptor binding affinity and transmembrane signaling.

Our previous studies indicated that amino acid residues 240-250 in the cysteine-rich region of the human insulin receptor alpha-subunit constitute a site in which insulin binds (Yip, C. C., Hsu, H., Patel, R. G., Hawley, D. M., Maddux, B. A., and Goldfine, I. D. (1988) Biochem. Biophys. Res. Commun. 157, 321-329). We have now constructed a human insulin receptor mutant in which 3 residues in this sequence were altered (Thr-Cys-Pro-Pro-Pro-Tyr-Tyr-His-Phe-Gln-Asp to Thr-Cys-Pro-Arg-Arg-Tyr-Tyr-Asp-Phe-Gln-Asp) and have expressed this mutant in rat hepatoma (HTC) cells. When compared with cells transfected with normal insulin receptors, cells transfected with mutant receptors had an increase in insulin-binding affinity and a decrease in the dissociation of bound 125I-insulin. Studies using solubilized receptors also demonstrated that mutant receptors had a higher binding affinity than normal receptors. In contrast, cells transfected with either mutant or normal receptors bound monoclonal antibodies against the receptor alpha-subunit with equal affinity. When receptor tyrosine kinase activity and alpha-aminoisobutyric acid uptake were measured, cells transfected with mutant insulin receptors were more sensitive to insulin than cells transfected with normal receptors. These findings lend further support therefore to the hypothesis that amino acid sequence 240-250 of the human insulin receptor alpha-subunit constitutes one site that interacts with insulin, and they indicate that mutations in this site can influence insulin receptor binding and transmembrane signaling.

Amino Acid Sequence↗
PubMed1989

Contour maps of auscultatory percussion in healthy subjects and patients with large intrapulmonary lesions.

Auscultatory percussion of the chest is a clinical examination method that has been purported to detect intrapulmonary masses by their effect on transmission of the percussion note to the posterior chest. Recent findings from this laboratory suggested that the sound of sternal percussion may actually travel through the chest cage and not the lung parenchyma. To investigate this possibility further, we recorded the sound produced by sternal percussion at 63 evenly spaced points over the posterior chest wall of 3 healthy subjects and 4 patients with large, discrete intrathoracic lesions in the right upper lobe (2 patients), left lower lobe, and left upper lobe (1 patient each). We constructed 3-dimensional contour maps of the indices of sound amplitude and frequency to view graphically the pattern of distribution of the sound. Examination of the maps revealed areas of increased amplitude in the zones of projection of some osseous structures, especially the scapulae, both in the healthy subjects and patients. No disturbances in the pattern reflecting the presence of mediastinal structures or intrathoracic lesions were found despite the existence of deeply situated lung masses as large as 10 cm in diameter. These findings support the argument that the sound of sternal percussion travels to the posterior chest predominantly through chest wall structures.

Auscultation↗
PubMed1989

Calcium-induced chromatin condensation and cyclin phosphorylation during chromatin condensation cycles in ammonia-activated sea urchin eggs.

Ammonia-activated sea urchin eggs undergo repeated cycles of DNA synthesis, nuclear envelope breakdown (NEB) and chromatin condensation. No mitotic spindle forms, nor do the eggs undergo cytokinesis. Ammonia-activated eggs exhibit a form of the cell cycle in which the nuclear cycle proceeds without segregation of the chromatin into daughter cells. We discuss here experiments that demonstrate that intracellular free calcium concentration controls the S phase-M phase transition in ammonia-activated eggs, as it does in fertilized embryos. Cyclins are proteins that are synthesized throughout the cell cycle and destroyed abruptly during each round of chromatin condensation. We find that cycles of cyclin phosphorylation and destruction occur coincident with chromatin condensation in ammonia-activated eggs. Cyclin phosphorylation also occurs in eggs treated with the tumour promoter, phorbol myristate acetate (PMA). There is no accompanying NEB or chromatin condensation, however, and the nucleus is insensitive to exogenously-generated calcium transients. These latter data indicate that cyclin synthesis and phosphorylation is not a sufficient condition for calcium-induced NEB in sea urchin embryos. PMA must fail to induce one of the necessary cell cycle initiation signals. We suggest that the missing signal is the activation of the cell cycle control protein p34cdc2, which we have shown to be phosphorylated at fertilization and which is phosphorylated in ammonia-activated eggs.

Ammonia↗
PubMed1989

Sleep quality and pulmonary function in the healthy elderly.

Loss of sleep causes deterioration of pulmonary function and ventilatory responsiveness in normal humans and in patients with chronic obstructive pulmonary disease. To evaluate the effects of variations in sleep quality on breathing, we studied 48 healthy elderly volunteers (mean age, 70 years). Electroencephalographically derived indices of sleep quality were correlated with spirometric performance, MIP, MEP, and waking SaO2. We found significant correlations between several indices of sleep quality and the spirometric measurements in the group as a whole, and striking correlations between sleep quality and PFTs in those with sleep efficiency less than or equal to 70 percent. We conclude that sleep disturbance may be related to poor performance on PFTs. These results suggest that spirometry should be performed on well-rested patients. The results also point to sleep quality as a potentially important variable in the management of patients with pulmonary disease.

Aged↗
PubMed1989

Delayed side effects of droperidol after ambulatory general anesthesia.

The incidence of postoperative effects of droperidol, in the hospital and at home the following night, after general anesthesia for minor outpatient procedures was evaluated in two groups of 50 patients each. Anesthetic techniques were identical except for the presence or absence of 1.25 mg of IV droperidol. There were no differences between the groups with regard to postoperative nausea, vomiting, pain, or time to discharge. In 23% of patients given droperidol, anxiety or restlessness developed after discharge from the ambulatory care unit. No patient not receiving droperidol had these reactions. It is suggested that the routine use of droperidol in all outpatients receiving general anesthesia may not be appropriate.

Adult↗
PubMed1988

Translational control of InsP3-induced chromatin condensation during the early cell cycles of sea urchin embryos.

The cycles of DNA synthesis and chromatin condensation in dividing cells are controlled by signals from the cytoplasm. Changes in the concentration of free calcium (Cai) in the cytoplasm control a variety of cellular functions and it has thus been suggested that observed variations in Cai during the cell cycle may be the cytoplasmic signal that co-ordinates nuclear and cytoplasmic division. We show here that increases in Cai induced by the calcium-releasing second messenger inositol 1,4,5-triphosphate (Ins(1,4,5)P3), or by calcium buffers, cause premature chromatin condensation and breakdown of the nuclear envelope in sea urchin (Lytechinus pictus) early embryos. Both natural and induced chromatin condensation are prevented by calcium chelators. The nucleus becomes sensitive to the Cai signal 45 min after fertilization, but remains insensitive if protein synthesis is prevented. Our experiments demonstrate that Cai regulates the behaviour of the nucleus during the cell cycle, suggest that Ins(1,4,5)P3 is a cell cycle messenger and indicate that there is an interaction between the protein and ionic signals that control the state of chromatin during the cell cycle.

Animals↗
PubMed1988

Evidence for chronic platelet hyperaggregability and in vivo activation in cyclosporin-treated renal allograft recipients.

Evidence for chronic in vivo platelet activation and hyperaggregability has been assessed in 21 renal allograft recipients. All patients received long term immunosuppression with cyclosporin (CS) and low dose prednisolone and were studied serially for 1 year post-transplantation. Spontaneous platelet aggregation in PRP was observed on 10 occasions in 5 patients. Platelet aggregation responses in PRP to low doses of ADP (0.5 and 1.0 microM) were significantly increased up to 1 year post-transplantation (p less than 0.02-less than 0.002). Total platelet nucleotide (ATP and ADP) content and release to 20 micrograms/ml of collagen were significantly decreased for 2 months post-transplantation, indicative of in vivo platelet activation (p less than 0.05-less than 0.002), and plasma PF4 levels were increased up to 1 year post-transplantation suggesting continued platelet activation of a lesser degree. Platelet sensitivity to the prostacyclin analogue Iloprost decreased after 1 month (p less than 0.05) and this persisted up to 1 year (p less than 0.01) compared with sensitivity at 1 week post-transplantation. These prothrombotic changes persisted when trough whole blood CS levels were within the therapeutic range and plasma creatinine levels were approaching or were in the normal range. These data indicate that CS-treated renal allograft recipients exhibit chronic platelet hyperactivity.

Adenine Nucleotides↗
PubMed1988

Tumor cell responses to inhibition of thymidylate synthase.

Whether inhibition of thymidylate synthase is lethal to a population of tumor cells depends upon three factors: 1) the dependence of the cells upon de novo synthesis of thymidine nucleotides; 2) the length of time enzyme is inhibited and the requirement for thymidine nucleotides during this period; and 3) the biochemical responses of the cells to the initial inhibition of enzyme, many of which interfere with maintenance of thymidylate synthase in an inhibited state. Following inhibition of thymidylate synthase, deoxyuridylate accumulates, as does the cellular content of thymidylate synthase. In addition, the initially formed enzyme-inhibitor complexes dissociate. These biochemical sequelae alter the effectiveness of the blockade of thymidylate synthase in a time-dependent, continuously-changing manner. Whether cell kill occurs depends on whether the dynamic balance of these factors allows a sufficiently low enzymatic activity to be maintained for a long enough period of time. An analysis of this interaction of factors leads us to the conclusions that efficient tumor cell kill with fluoropyrimidines is best attained by combination with reduced folate cofactors and inhibitors of deoxypyrimidine biosynthesis. Each of these agents modifies the response of tumor cells with the result that the fluorodeoxyuridylate-induced inhibition of thymidylate synthase is maintained. This analysis also suggests that folate analogs inhibitory to thymidylate synthase are more compatible than pyrimidine analogs with inhibition of thymidylate synthase as an approach to cancer chemotherapy.

Animals↗
PubMed1988

Sex differences in high density lipoprotein cholesterol in urban blacks.

Descriptive data on high density lipoprotein (HDL) cholesterol in the black urban population of the United States are limited. We examined 119 men and 130 women aged 21-70 years who were attending a screening clinic at Cook County Hospital in Chicago, Illinois, in 1985-1986 for minor complaints; all participants were black. For men, lipid values were: total cholesterol, 209.5 +/- 50.6, HDL cholesterol, 55.2 +/- 16.5; for women, values were: total cholesterol, 215.6 +/- 47.4, HDL cholesterol, 59.2 +/- 17.2. Correlates of HDL cholesterol were different in men and women. Alcohol consumption and body mass index were significantly related to HDL cholesterol in men; however, education was the only significant factor among women. It was anticipated that the increased obesity among the women in this sample (mean body mass index, 31 kg/m2; range, 18.4-50.0 kg/m2) compared with men (mean body mass index, 27 kg/m2; range, 19.4-45.0 kg/m2) would explain part of the narrowing of the gap between the sexes in HDL cholesterol values. The association between HDL cholesterol and body mass index among women, however, was weak and nonsignificant. The increased susceptibility of black women to coronary artery disease has not been adequately explained and undoubtedly reflects a complicated interaction of epidemiologic factors.

Adult↗
PubMed1987

Pediatric phase I trial and pharmacokinetic study of trimetrexate.

Trimetrexate, a new nonclassical antifolate, was evaluated in a phase I trial in children with refractory cancer including nine with acute leukemia and 21 with solid tumors. The drug was administered as an i.v. bolus injection weekly for three doses, and courses were repeated every 28 days. The dose ranged from 35 to 145 mg/m2. Thirty patients who received a total of 33 courses were evaluable for toxicity, including 19 who were evaluable for hematological toxicity. The maximally tolerated dose for patients with a solid tumor and leukemia was 110 mg/m2. The dose-limiting toxicities were myelosuppression, mucositis and a pruritic, diffuse maculopapular rash. Other side effects observed included transient, mild elevations of serum transaminases, mild nausea and vomiting, and a local phlebitis at the site of injection at higher dose levels. A single patient with delayed drug clearance had evidence of renal toxicity with a transient increase in serum creatinine. The pharmacokinetics of trimetrexate were studied in 25 patients over the entire dose range. There was considerable interpatient variability in total drug clearance (range 9.2 to 215 ml/min/m2) and half-life (2.1 to 20 h). There was a suggestion of a correlation between plasma concentration at 24 h and the development of hematological toxicity at the highest dose level. Trimetrexate was cleared primarily by biotransformation with renal clearance accounting for only 10% of total clearance. Two metabolites of trimetrexate which inhibit the enzyme dihydrofolate reductase were identified in the urine. One of these appears to be a glucuronide conjugate.

Adolescent↗
PubMed1987

Immobilization and assay of low-molecular-weight phosphomannosyl receptor in multiwell plates.

A novel sensitive binding assay for quantitation of a low-molecular-weight phosphomannosyl receptor (41-46 K) was devised. The receptor was immobilized by immunochemical means in the wells of polystyrene multiwell plates. The lysosomal enzyme ligand, testicular beta-galactosidase, was added and receptor-bound beta-galactosidase was measured by conventional colorimetric analysis using p-nitrophenyl beta-galactoside as substrate. Inhibitors of the binding of beta-galactosidase to the receptor were removed prior to addition of beta-galactosidase and did not interfere with the assay. Low-molecular-weight phosphomannosyl receptor was readily quantitated in the range of 4 to 100 ng of receptor protein. Binding of beta-galactosidase to the receptor was specifically inhibited by 5 mM mannose 6-phosphate. The receptor exhibited optimum binding of beta-galactosidase at pH 5.7 and was saturated with beta-galactosidase at 320 munits/ml in the presence of 20 mM MnCl2. The requirement for MnCl2 was greatly diminished at higher concentrations of beta-galactosidase. Application of the assay procedure to the quantitation of the low-molecular-weight phosphomannosyl receptor in mammalian tissues is discussed.

Animals↗