Biomedical subjects
Publications and source records attributed to G Rao.
Epidermoid cyst in a six and half year old male child is reported. The cyst was quite huge thereby reducing the splenic tissue. Histologically the epithelial lining showed dysplastic changes and unusual calcification of the collagenous connective tissue.
Modification of DNA bases in mammalian chromatin in aqueous suspension by ionizing radiation generated free radicals was investigated. Argon, air, N2O, and N2O/O2 were used for saturation of the aqueous system in order to provide different radical environments. Radiation doses ranging from 20 to 200 Gy (J.kg-1) were used. Thirteen products resulting from radical interactions with pyrimidines and purines in chromatin were identified and quantitated by using the technique of gas chromatography/mass spectrometry with selected-ion monitoring after acidic hydrolysis and trimethylsilylation of chromatin. The methodology used permitted analysis of the modified bases directly in chromatin without the necessity of isolation of DNA from chromatin first. The results indicate that the radical environment provided by the presence of different gases in the system had a substantial effect on the types of products and their quantities. Some products were produced only in the presence of oxygen, whereas other products were detected only in the absence of oxygen. Products produced under all four gaseous conditions were also observed. Generally, the presence of oxygen in the system increased the yields of the products with the exception of formamidopyrimidines. Superoxide radical formed in the presence of air, and to a lesser extent in the presence of N2O/O2, had no effect on product formation. The presence of oxygen dramatically increased the yields of 8-hydroxypurines, whereas the yields of formamidopyrimidines were not affected by oxygen, although these products result from respective oxidation and reduction of the same hydroxyl-adduct radicals of purines. The yields of the products were much lower than those observed previously with DNA.
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Age-related changes in the activities of superoxide dismutase, catalase, and glutathione peroxidase were determined in brain, heart, hepatocytes, intestinal mucosa, and kidney from male Fischer F344 rats. Superoxide dismutase activity decreased significantly with age in all five tissues studied. The activity of catalase decreased with age in brain, hepatocytes, and kidney while glutathione peroxidase activity decreased significantly with age only in intestinal mucosa and kidney. The relative levels of superoxide dismutase, catalase, and glutathione peroxidase mRNA were measured in brain, hepatocytes, and kidney. An age-related decrease in SOD and catalase mRNA was observed for brain, hepatocytes, and kidney. GPX mRNA levels decreased with age in hepatocytes and kidney but did not change with age in brain. In general, the age-related changes in the activities of SOD, catalase, and GPX were paralleled by a similar change in the relative level of the mRNAs coding for these enzymes.
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The effects of aging and dietary restriction on the expression of several enzymes (superoxide dismutase, catalase and glutathione peroxidase) that are involved in free radical detoxification were studied in liver tissue from male Fischer F344 rats. The expression (i.e., activities and mRNA levels) of superoxide dismutase (Cu-Zn) and catalase decreased with age in liver. Dietary restriction (40% restriction of energy intake) increased the activities of superoxide dismutase (24 to 38%) and catalase (64 to 75%) in liver at 21 and 28 mo of age. Glutathione peroxidase activity in liver of diet-restricted rats was significantly higher (37%) at 28 mo of age than that of rats fed ad libitum. The age-related changes in the relative levels of mRNA for superoxide dismutase, catalase and glutathione peroxidase paralleled the changes in the activities of these enzymes in rats fed ad libitum or rats fed the restricted diet. Thus, the changes in the activities of superoxide dismutase, catalase and glutathione peroxidase with age and dietary restriction appear to arise from changes in the levels of mRNAs coding for these enzymes. Free radical damage, as measured by thiobarbituric acid-reactive material and lipofuscin accumulation, was lower in diet-restricted rats than in rats fed ad libitum.
Studies were designed to explore the possibility that sulfated polysaccharides had the potential to prevent human leukocyte elastase (HLE)-induced lung injury. Arteparon (GAGPS), heparin, heparan sulfate, chondroitin sulfate, and dextran sulfate, but not dextran, inhibited HLE-mediated hydrolysis of succinyl-ala2-val-pNA. GAGPS, used as a paradigmatic sulfated polysaccharide, was a potent inhibitor of elastolysis in vitro. GAGPS given intratracheally prevented acute injury and emphysema in hamsters when administered up to 8 h before HLE insufflation. The results suggest that sulfated polysaccharides may be potent inhibitors of HLE-mediated lung injury.
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The activities of superoxide dismutase (Cu/Zn) and catalase were observed to decrease significantly between 6 and 29 months of age in rat liver. The decrease in superoxide dismutase and catalase activity was paralleled by a decrease in the levels of the mRNA species coding for these enzymes and the nuclear transcription of the superoxide dismutase and catalase genes. Life-long dietary restriction was shown to increase the expression (i.e. activities, mRNA levels, and nuclear transcription) of superoxide dismutase and catalase in liver tissue from 18-month-old rats.
One aim of this in vitro investigation was to determine the effect of substituting four phenols and two methacrylates with vinyl functions on the dentin bond strengths of several new experimental dentin bonding agents. Another objective was to determine the effect of postextraction age and dentin level within the tooth on tensile bond strengths of these toluene diisocyanate-derived adhesives. Extracted third molars were divided into postextraction age groups and sectioned into three slices approximately 400 microns thick. The four substituted phenols were: eugenol, o-methoxyphenol, o-chlorophenol, and p-cresol. Substituted methacrylates with vinyl ligands were 2-hydroxyethyl methacrylate (HEMA) and 6-hydroxyhexyl methacrylate (HHMA). Results showed that adhesives made with o-chlorophenol, p-cresol, and methoxyphenol with HEMA were the best, while those made with eugenol and HHMA were the worst. The post extraction age of the tooth and the dentin depth had no consistent effect on most adhesive bond strengths which were generally around 10.3 MPa (1500 psi).
Late transcription of bacteriophage Mu, which results in the expression of phage morphogenetic functions, is dependent on Mu C protein. Earlier experiments indicated that Mu late RNAs originate from four promoters, including the previously characterized mom promoter. S1 nuclease protection experiments were used to map RNA 5' ends in the three new regions. Transcripts were initiated at these points only in the presence of C and were synthesized in a rightward direction on the Mu genome. Amber mutant marker rescue analysis of plasmid clones and limited DNA sequencing demonstrated that these new promoters are located between C and lys, upstream of I, and upstream of P within the N gene. A comparison of the promoter sequences upstream from the four RNA 5' ends yielded two conserved sequences: the first (tA . . cT, where capital and lowercase letters indicate 100 and 75% base conservation, respectively), at approximately -10, shares some similarity with the consensus Escherichia coli sigma 70 -10 region, while the second (ccATAAc CcCPuG/Cac, where Pu indicates a purine), in the -35 region, bears no resemblance to the E. coli -35 consensus. We propose that these conserved Mu late promoter consensus sequences are important for C-dependent promoter activity. Plasmids containing transcription fusions of these late promoters to lacZ exhibited C-dependent beta-galactosidase synthesis in vivo, and C was the only Mu product needed for this transactivation. As expected, the late promoter-lacZ fusions were activated only at late times after induction of a Mu prophage. The C-dependent activation of lacZ fusions containing only a few bases of the 5' end of Mu late RNA and the presence of altered promoter sequences imply that C acts at the level of transcription initiation.
The interaction of angiotensin converting enzyme (ACE) inhibition and atrial natriuretic factor (ANF) was investigated in six supine, sodium-replete, normal volunteers who received captopril (10 mg i.v. bolus followed by 10 mg/hr constant infusion) or vehicle superimposed on background 3-hour, constant, low-dose (1.5 pmol/kg/min) infusions of human ANF (99-126). Plasma converting enzyme activity was significantly inhibited but this had no effect on endogenous plasma ANF concentrations. ANF infusions, with or without captopril, caused similar increases in plasma ANF concentrations, and calculated metabolic clearance rates for ANF were unchanged. Similarly, blood pressure, heart rate, renal blood flow, glomerular filtration rate, and renal electrolyte excretion, including ANF-induced natriuresis, were unaffected by captopril. The combination of ANF plus captopril produced a significant increase in plasma aldosterone (79 +/- 8 vs. 60 +/- 6 pmol/l, p less than 0.05), cortisol (406 +/- 52 vs. 265 +/- 29 nmol/l, p less than 0.01), adrenaline (119 +/- 21 vs. 76 +/- 10 pg/ml, p less than 0.05), and noradrenaline (319 +/- 49 vs. 215 +/- 38 pg/ml, p less than 0.05) compared with time-matched placebo data. Converting enzyme inhibition, in the absence of major changes in blood pressure or renal blood flow, has little effect on ANF metabolism or renal bioactivity. However, ACE inhibition and ANF combined may interact to increase activity of the hypothalamo-pituitary-adrenal axis and sympathetic nervous system by unknown mechanisms.
A 64-year-old woman presented in shock. The computed tomography (CT) scan confirmed rupture of the left diaphragm with strangulation. Three days after surgery, the patient developed herniation of abdominal contents on the right side with cardiorespiratory collapse. Marlex mesh was used to repair on the right side. Postoperatively, she needed partial gastrectomy for massive duodenal ulcer bleeding. A dual chamber pacemaker was used to correct the complete heart block.
Of the total number of pacemakers implanted each year, 6% must eventually be replaced because of infection, lead failure, or other problems. Often however, removal of the pacing leads is precluded by scarring at the tip of the leads. Because abandoned leads can cause serious problems, we initiated the present study to test the feasibility of using a laser to remove such leads. After performing in vitro experiments to establish the laser settings required for severing leads, we implanted 6 leads, from 4 different manufacturers, in 3 dogs. Five weeks later, we passed a laser fiber through each lead to the tip and delivered a 10-watt impulse for 2 seconds, which resulted in the successful removal of all the leads. When the dogs were killed 3 days later, postmortem examination revealed no thromboembolism in the heart or lungs and no myocardial damage. Subsequent experiments in 3 human cadaver hearts-involving leads implanted for 5 years, 2 years, and 2 months-yielded the same satisfactory results as did the canine experiments.
Stimulation of hepatocytes by the tumor promoter phorbol 12-myristate 13-acetate (PMA) caused translocation of cytosolic Ca2+/phospholipid-dependent protein kinase C (PK-C). The major part of PK-C activity (greater than 80%) was associated with the membrane fraction after 30 min. During the following 6 h protein kinase C activity decreased to less than 10%. Minor amounts of Ca2+/phospholipid-independent PK-C activity were found in the cytosol fraction at all times; they temporarily increased 2.5-fold with PMA and decreased after 1 h. Cyclosporin A did not affect the translocation of PK-C from the cytoplasm to the membrane fraction, but the decrease of PK-C activity following translocation was blocked. No marked increase of Ca2+/phospholipid-independent PK-C activity was observed in the cytosol in the presence of cyclosporin A. Leupeptin, which is known to inhibit Ca2+-requiring non-lysosomal proteinases (e.g. calpain), showed an effect similar to cyclosporin A. Both agents reduced proteolytic degradation of cellular proteins observed in isolated hepatocytes after PMA treatment. Ca2+-ionophore A23187 in high doses (greater than 10(5) M) partly reversed cyclosporin A and leupeptin action.
Senile plaques (SPs), especially, and neurofibrillary tangles are important pathologic markers for the diagnosis of Alzheimer's disease (AD), but neither is pathognomonic for AD. We hypothesize that elevations in levels of phosphomonoesters, precursors of membrane phospholipids, occur early in the pathogenesis of AD and precede the appearance of SPs. In contrast, elevations in levels of phosphodiesters, breakdown products of phospholipids, reflect degeneration of neural membranes and will correlate with the appearance of SPs. Correlative phosphorus-31 magnetic resonance spectroscopy and morphologic studies conducted to test this hypothesis disclosed that elevations in levels of phosphomonoesters had a negative correlation with the numbers of SPs, and elevations in levels of phosphodiesters had a positive correlation with the numbers of SPs. No correlations were observed for either membrane parameter and neurofibrillary tangles. These findings support our hypothesis and suggest that aberrations in the synthesis of membrane phospholipids are early metabolic events in the pathogenesis of AD.
Levels of brain creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD) in CSF after cardiac arrest were studied in dog models. Ventricular fibrillation cardiac arrest lasting 10 min or asphyxiation cardiac arrest lasting 0-10 min was followed by cardiopulmonary resuscitation and 96-h intensive care. Outcome was scored as neurologic deficit (0% = normal, 100% = brain death) and overall performance category (1 = normal, 5 = death). Both measures correlated with EEG return time after asphyxiation cardiac arrest, but not after ventricular fibrillation cardiac arrest. Peak activity of enzymes in CSF at 48-72 h post arrest correlated with outcome, and CK was the best predictor. Brain histopathologic damage score at autopsy 96 h post arrest correlated with CK level in CSF (r = 0.79, n = 39) and neurologic deficit (r = 0.70, n = 50). Ischemic neuronal changes occurred after ventricular fibrillation cardiac arrest of 10 min, and neuronal changes plus microinfarcts occurred after asphyxiation cardiac arrest of 1.5-10 min. Brain enzymes were decreased at 6 h post arrest in regions with worst histologic damage (gray matter of neocortex, hippocampus, caudate nucleus, cerebellum). Brain CK decreased further, ASAT remained low, and LD increased at 72 h after arrest. The temporal changes in CK level paralleled the temporal ischemic neuronal changes in the brain, and time to peak activity was unaffected by the severity of the ischemic insult. Peak activity of individual enzymes in CSF was determined predominantly by the brain concentration, but was also influenced by rate of decomposition. This "chemical brain biopsy method" represents a useful adjunctive tool to predict permanent, severe brain damage during comatose states after cardiac arrest and resuscitation.
A case of alcoholic beverage sensitivity is described which presented as acute bronchospasm. Such reactions in asthmatics are not uncommon, though their severity may be underestimated in the presence of intoxication. Indeed, such patients may be dismissed as suffering only from the effects of intoxication with obvious consequences.