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Biomedical subjects

B Patel

Publications and source records attributed to B Patel.

At least 163 records · Page 9Linked to original sources

Effect of a partial trisomy in the mouse upon cellular and nuclear RNA.

In a previous paper (Rake and Edwards, 1987) it was shown that the majority of the chromatin from trisomic mouse cells has nucleosomes with a smaller repeat length of DNA than the nucleosome repeat length of normal cells. Here it is shown that the RNA content of the total cell and of the nuclei is the same in all tissues studied, in both normal and trisomic cells. However, the amount per unit time or rate of RNA synthesis is depressed in the trisomic liver and brain nuclei. The depression of RNA synthesis could not be specified to the small trisomic section of the chromatin but instead must reflect the overall nuclear activity. These results, along with those of Devlin et al. (1988), indicate that the trisomic condition alters a substantial part of nuclear organization and activity, not just the small trisomic part.

Animals↗

Do selenium and glutathione inhibit the toxic effects of mercury in marine lamellibranchs?

The effect of selenium (SeO2) and glutathione (GSH) on the bioaccumulation of mercury (HgCl2) and on the activities of lysosomal enzymes in four species of tropical estuarine lamellibranchs is reported. A definite correlation between mercury levels in the external medium and tissue uptake and physiological behaviour--opening and closing of shell valves, response to mechanical stimulus, mucus secretion, and incidence of bleeding--was evident. In the clams exposed to Hg (range 0.1-5.0 mg l-1), bioaccumulation was dependent on the ambient concentration of Hg. The highest bioaccumulation of Hg occurred during the initial 24 h exposure period. Further exposure of up to 7 days did not increase the body burden of Hg. Of the four bivalve species exposed to 0.1 mg Hg l-1, Perna viridis showed the highest levels of Hg (approximately 47 ppm) followed by Anadara granosa, A. rhombea (approximately 25 ppm) and Meretrix casta (approximately 9 ppm). The uptake of Hg by A. granosa was greatly reduced by GSH, whereas Se enhanced it by 50% when administered in combination with Hg. However, the presence of Hg did not influence the uptake of Se. Exposure to combined GSH and Hg resulted in almost complete inhibition of Hg uptake in all four bivalve species. Prior exposure to GSH, however, did not have the same influence on their uptake of Hg. Nevertheless, exposure of clams to GSH following initial exposure to Hg resulted in complete depuration of accumulated Hg. The activities of lysosomal enzymes--arylsulfatase, acid phosphatase, beta-galactosidase and beta-glucuronidase--varied considerably. Treatment with Hg and GSH, separately and in combination, significantly enhanced the levels of beta-galactosidase (P less than 0.05) and beta-glucuronidase (P less than 0.001) in the digestive gland after 96 h exposure. Although Se increased beta-glucuronidase activity (P less than 0.001), it had no effect on beta-galactosidase. On exposure to Hg + Se the activity of both enzymes decreased, except in P. viridis where it increased by 39%. The results show unequivocally that Se does not offer any protection against the toxic effects of mercury in marine lamellibranchs, whereas in many marine vertebrates it does. GSH, a thiol-rich tripeptide, on the other hand, completely nullifies the toxic effects of Hg, both in vivo and in vitro.

Animals↗

Factors that determine the occurrence of reperfusion arrhythmias.

The determinants of reperfusion arrhythmias were investigated in 63 open-chest dogs undergoing a 25-minute coronary artery occlusion followed by reperfusion. Heart rate correlated positively with the occurrence of reperfusion ventricular tachycardia (VT) and ventricular fibrillation (VF). Collateral flow during ischemia (radioactive microspheres) exhibited a strong negative correlation with the incidence of both VT and VF upon reperfusion. Importantly, a sensitive coupling was present, whereby small differences in flow were associated with large differences in rhythm disorders. The rise in intramyocardial CO2 tension (another index of severity of ischemia) was greater in dogs exhibiting reperfusion VT (p less than 0.001) and VF (p less than 0.08); however, this variable was significantly correlated with collateral flow (r = -0.57, p less than 0.01). The size of the occluded coronary bed, determined by postmortem perfusion, was not consistently related to VT; within a given range of occluded bed sizes, the incidence of VT was inversely related to collateral flow. Thus, reperfusion-induced VT is relatively independent of the size of the occluded bed, and is determined primarily by the degree of myocardial hypoperfusion. In contrast, VF did not develop with occluded beds less than 25% of the left ventricular mass; above this critical occluded bed size, its incidence was inversely related to collateral perfusion. Reperfusion VF is therefore determined by the association of a large occluded bed with a poor collateral flow. This study identifies and systematically analyzes three major determinants of reperfusion arrhythmias: (1) the severity of antecedent ischemia, estimated either from the degree of flow reduction or the rise in intramural CO2 tension; (2) the amount of ischemic/reperfused myocardium; and (3) the heart rate. In addition to conceptual interest and clinical implications, the findings have important implications for the design of future studies aimed at evaluating antiarrhythmic interventions in experimental models.

Animals↗

Neutropenic colitis: evaluation with computed tomography.

The computed tomography findings of 10 patients with neutropenic colitis are described and illustrated. Seven of these patients had leukemia, one had lymphocytic lymphoma, and two had systemic lupus erythematosus. All patients had colon wall thickening which was either isodense with the normal bowel tissue or showed areas of intramural low density. Air in the thickened bowel wall was seen in six patients. These computed tomography findings in neutropenic patients with fever, abdominal pain, and diarrhea should suggest the diagnosis in most instances, resulting in prompt treatment of this usually life-threatening entity.

Adult↗

Preoperative evaluation with radionuclide brain scanning and computerized axial tomography of the brain in patients with breast cancer.

To determine the roles of radionuclide brain scanning and computerized tomography of brain in the pretreatment evaluation of patients with primary and locoregional recurrence of breast cancer, we reviewed the clinical and radiologic findings in 226 patients with breast cancer who underwent one of these scans either preoperatively or within 6 weeks of operation and in 34 patients presenting with locoregional recurrence. Four of 131 radionuclide brain scans in primary breast cancer suggested calvarial metastasis, and the findings were confirmed with bone scans and skull radiographs. One of 95 computerized tomographic scans of the brain showed brain metastasis, and this patient had profound neurologic deficits. With respect to locoregional recurrence, the results of 2 of 23 radionuclide scans and 1 of 11 computerized tomographic scans were positive. All three patients had clinical evidence for brain metastasis. We conclude that in the absence of signs and symptoms, routine evaluation for brain metastasis is not justified in primary and locoregional recurrence of breast cancer.

Brain Neoplasms↗

Quantification of myocardial infarction during coronary occlusion and myocardial salvage after reperfusion using cardiac imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile.

Myocardial imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile was investigated as a means to assess myocardial infarct size during coronary occlusion and to quantify the extent of salvaged myocardium after coronary occlusion followed by reperfusion. Open chest dogs underwent either a permanent coronary artery occlusion (Group 1, n = 16) or a 2 h occlusion followed by reperfusion (Group 2, n = 15). Animals in both groups were killed 48 h after occlusion. During coronary occlusion, 23 of the 25 dogs that survived the coronary occlusions had abnormal myocardial scintigrams. The scintigraphic perfusion defect size correlated well with the pathologic infarct size (r = 0.85 and 0.95 by planar and tomographic imaging, respectively). The planar scintigraphic defect size, but not the tomographic defect size, overestimated the pathologic size. The planar scintigraphic defect size observed during coronary occlusion was markedly reduced 48 h after reperfusion (24.8 +/- 12.8% to 10.6 +/- 9.7% of the left ventricle, p less than 0.003). The uptake of technetium-99m hexakis 2-methoxyisobutyl isonitrile in the ischemic myocardium increased significantly 48 h after reperfusion (p less than 0.003) and correlated with the increase in regional myocardial blood flow, as assessed by radioactive microspheres (r = 0.83, p less than 0.01). Thus, myocardial imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile allows reliable demonstration of the presence of acute infarction, estimation of infarct size and quantification of the extent of salvaged myocardium after coronary reperfusion.

Animals↗

Pancreatic transplantation: scintigraphy, US, and CT.

Twenty-one patients with insulin-dependent diabetes mellitus received simultaneous renal and segmental pancreatic transplants. A retrospective analysis of 112 real-time ultrasound (US) images, 108 technetium-99m glucoheptonate scinti-scans, 55 computed tomography (CT) scans, and 11 cystograms was performed. Complications that were observed included pancreatic transplant rejection, pancreatitis, arteriovenous occlusions, hemorrhage, abscesses, and extravasation at the pancreaticocystostomy site. Scintigraphy is a sensitive indicator of normal transplant function but is non-specific when findings are abnormal. Real-time US aids in the differentiation of acute rejection from pancreatitis and arteriovenous occlusion. CT is helpful for evaluation of postoperative complications. Imaging may play an important role in the noninvasive management of pancreatic transplants.

Adult↗

Increased levels of protein C activity, protein C concentration, total and free protein S in nephrotic syndrome.

Plasma protein C (PC) antigen concentration has been shown to be normal or increased in patients with proteinuria. However, the available data concerning PC anticoagulant activity in nephrotic syndrome (NS) are limited. We measured plasma PC antigen concentration. PC anticoagulant activity, total and free protein (PS) concentrations, and antithrombin III (AT-III) antigen concentration in 21 adult patients with NS. The results were compared with those obtained in a control group of normal volunteers. PC antigen concentration and its anticoagulant activity were significantly increased in the NS group when compared with the normal control group. Likewise, plasma total and free PS values were significantly higher in the NS patients than the corresponding values found in the control group. In contrast, plasma AT-III antigen concentration was significantly reduced in patients with NS. A negative correlation was found between plasma PC and AT-III levels. These observations suggest that increased plasma PC concentration and anticoagulant activity in NS may afford some protection against the thrombotic diathesis associated with antithrombin deficiency and other coagulation abnormalities in this otherwise hypercoagulable state.

Adolescent↗

Dietary marine lipids after the course of autoimmune disease.

Dietary marine lipids reduce both mortality and the severity of glomerulonephritis in inbred murine strains which develop spontaneous autoimmune disease. The protective effects of marine lipids appears to be accounted for by the major n-3 fatty acids in these preparations, 20:5 and 22:6. The n-3 fatty acids in dietary fish oil are extensively incorporated into several lipid classes in the spleen of autoimmune mice, including phosphatidylinositol, phosphatidylethanolamine, plasmalogens and saturated ether-linked phospholipids as well as diacylphosphoglycerides. The effects of dietary marine lipids on autoimmune disease in experimental models are highly specific. Careful controlled trials will be required to establish the role of dietary marine lipids in the therapy of human autoimmune disease.

Animals↗

The effect of alcohol on nocturnal gastroesophageal reflux.

The effect of 120 mL (4 oz) of scotch whiskey (40% alcohol) on nocturnal gastroesophageal reflux was studied by ambulatory esophageal pH monitoring. Seventeen healthy volunteers were studied on two occasions, using a computerized radiotelemetric esophageal pH monitoring system. The subjects were given the alcohol during the second session, three hours after the evening meal, and went to bed at their usual time. Seven of the 17 subjects had prolonged supine reflux episodes on the night of alcohol ingestion. These lasted an average of 47.1 minutes (23.2 to 91.8 minutes) and occurred on an average of 3 1/2 hours after ingestion of whiskey and 1.4 hours after lying down. None of the subjects had these episodes on the control night. There was also a significant acidic shift in the cumulative percentage of data points below a pH of 3 and a pH of 4 in the supine position on the night of alcohol ingestion compared with the control night. This study has shown that there was a significant exposure of the distal esophagus to acid and that the normal acid clearance of the esophagus in the supine position was impaired after only moderate amounts of alcohol.

Adult↗

Isolation and characterization of a vinculin cDNA from chick-embryo fibroblasts.

A chick-embryo fibroblast lambda gt11 cDNA library was screened with affinity-purified antibodies to chick gizzard vinculin. One recombinant was purified to homogeneity and the fusion protein expressed in Escherichia coli strain C600. The fusion protein was unstable, but polypeptides that reacted with vinculin antibodies, but not non-immune immunoglobulin, were detected by Western blotting. The recombinant contained a single EcoRI fragment of 2891 bp with a single open reading frame. The deduced protein sequence could be aligned with that of six CNBr-cleavage peptides and two tryptic peptides derived from chicken gizzard vinculin. AUG-247 has tentatively been identified as the initiation codon, as it is contained within the consensus sequence for initiation sites of higher eukaryotes. The cDNA lacks 3' sequence and encodes 74% of the vinculin sequence, presuming the molecular mass of vinculin to be 130,000 Da. Analysis of the deduced sequence showed no homologies with other protein sequences, but it does display a triple internal repeat of 112 amino acid residues covering residues 259-589. The sequences surrounding the seven tyrosine residues in the available sequence were aligned with the tyrosine autophosphorylation consensus sequence found in protein tyrosine kinases. Tyr-822 showed a good match to this consensus, and may represent one of the two major sites of tyrosine phosphorylation by pp60v-sre. Northern blots showed that the 2.89 kb vinculin cDNA hybridized to one size of mRNA (approx. 7 kb) in chick-embryo fibroblasts, chick smooth muscle and chick skeletal muscle. Southern blots revealed multiple hybridizing bands in genomic DNA.

Amino Acid Sequence↗

Analysis of reported randomized trials of streptokinase therapy for acute myocardial infarction in the 1980s.

Trials of intracoronary (IC) and intravenous (IV) streptokinase (SK) therapy for myocardial infarction have shown variable effects on mortality and left ventricular (LV) function. A pooled analysis of 10 randomized trials involving a total of 14,355 patients was performed to look for overall trends in the change in mortality within 6 weeks (group A) and after 6 weeks (group B) of follow-up, and the change in LV function. All 10 trials, 7 with IC and 3 with IV SK, were randomized after 1980. There was a significant reduction in mortality risk in patients in group A treated with IV SK (pooled odds ratio = 0.81, 95% confidence interval = 0.73 to 0.90, p less than 0.001). In contrast, no significant differences in mortality were detected in patients in group B treated with IV SK or in patients in either group treated with IC SK. Two IV SK trials that prospectively stratified patient population according to duration of symptoms showed a greater reduction in mortality with administration of SK therapy within 3 hours of onset of symptoms. Analysis of LV function was performed before, within 96 hours after and 1 to 4 weeks after SK therapy. Only 2 of 7 IC SK trials showed significantly greater improvement in global LV ejection fraction in SK group compared with a control group, both showing improvement in LV function between early and late after treatment. Thus, IV SK therapy significantly reduces short-term risk of death after acute myocardial infarction; 2 trials show a greater reduction in mortality risk with earlier institution of IV SK therapy.

Clinical Trials as Topic↗

Isolation and characterization of a cDNA encoding a chick alpha-actinin.

We have isolated and sequenced a 2.1-kilobase cDNA encoding 86% of the sequence of alpha-actinin. The cDNA clone was isolated from a chick embryo fibroblast cDNA library constructed in the expression vector lambda gt11. Identification of this sequence as alpha-actinin was confirmed by immunological methods and by comparing the deduced protein sequence with the sequence of several CNBr fragments obtained from adult chicken smooth muscle (gizzard) alpha-actinin. The deduced protein sequence shows two distinct domains, one of which consists of four repeats of approximately 120 amino acids. This region corresponds to a previously identified 50-kDa tryptic peptide involved in formation of the alpha-actinin dimer. The last 19 residues of C-terminal sequence display an homology with the so-called E-F hand of Ca2+-binding proteins. Hybridization analysis reveals only one size of mRNA (approximately 3.5 kilobases) in fibroblasts, but multiple bands in genomic cDNA.

Actinin↗