Biomedical subjects
Publications and source records attributed to K Patel.
Influenza virus causes susceptible cells to undergo haemagglutination, haemolysis and oxygen radical formation. Each activity is the result of an interaction between the haemagglutinin (HA) glycoprotein and the cell plasma membrane, and appears to involve three discrete functions of the HA glycoprotein.
Permeability changes elicited in Lettre cells by influenza virus at pH 5.3 were maintained when the pH was shifted to 7.4. Permeability changes elicited by Sendai virus at pH 7.4 were maintained when the pH was shifted to 5.3. In each case permeability changes at the new pH were sensitive to inhibition by extracellular Ca2+. The time at which the pH was shifted was critical: if the shift was made prior to the onset of permeability changes, no subsequent changes occurred. It is concluded that the pH-sensitive event, namely virus-cell fusion, is related to the induction of permeability changes through attainment of some type of 'threshold' level of membrane damage.
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Haemolytic paramyxoviruses interact with cells in the following way: a potentially leaky viral envelope fuses with the plasma membrane, creating a hydrophilic pore of approximately 1 nm in diameter; this allows ions and low molecular weight compounds, but not proteins, to leak into and out of cells. Other viruses act similarly if the pH is reduced to 5. Leakage (measured by collapse of membrane potential, by movement of monovalent cations and by loss of phosphorylated intermediates from cells) is prevented by extracellular Ca2+. Ca2+ does not affect binding or fusion of virus to cells. It inhibits leakage as well as preventing it, and it aids in the recovery (i.e. the restoration of non-leakiness) of cells. Certain 'anti-Ca2+' drugs have an opposite effect. Experiments with the bee venom protein melittin, with the alpha-toxin of Staphylococcus aureus and with activated complement, show that the lesions produced by these agents, too, are sensitive to extracellular Ca2+ and to 'anti-Ca2+' drugs. The mechanisms of these effects are discussed.
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The effect of infrarenal cross-clamping of the aorta on regional splanchnic and renal circulations was studied in seven dogs. Regional blood flow was determined with differentially labeled microspheres (9 and 15 micron in diameter) that were injected simultaneously into the left atrium. Blood flow was measured 30 minutes after surgical preparation was completed (stage I), 20 minutes after infrarenal aortic cross-clamping (stage II), and 20 minutes after supplemented sodium nitroprusside infusion (stage III). Infrarenal aortic cross-clamping was accompanied by a slight increase in the cardiac output (CO) without significant changes in mean arterial pressure (MAP). Blood flow through the gut, hepatic artery, and cortical layer of the kidneys, as determined with 15-micron spheres, was not changed. Nonentrapment of 9-micron spheres in the gut and renal cortex was increased substantially. Blood flow through the juxtamedullary layer of the kidneys was increased. Sodium nitroprusside supplementation decreased MAP by 30%; CO values returned to baseline level. Hepatic artery blood flow, compared with both baseline values and values during aortic cross-clamping, increased significantly. Blood flow, determined with 15-micron spheres, through the gut and renal cortex did not change, and nonentrapment of 9-micron spheres decreased to baseline values. The data suggest a certain shift of blood flow to the juxtamedullary layer of the kidneys during aortic cross-clamping and normalization of intrarenal blood flow distribution during supplemented sodium nitroprusside infusion. Controlled vasoplegia with sodium nitroprusside may help modify peripheral circulatory disturbances in the kidneys and splanchnic system during infrarenal aortic cross-clamping.
Haemolysis by Sendai virus, alpha-toxin, and activated complement is inhibited by high concentrations of divalent cations. In Daudi cells, sublytic amounts of these agents induce the following changes: collapse of surface membrane potential, uptake of Na+ and loss of K+ from cells, and leakage of phosphorylated metabolites from cells. The changes induced by Sendai virus and complement are sensitive to physiological concentrations of extracellular Ca2+. It is concluded that fluctuations in plasma Ca2+ concentration may affect the damaging action of certain pore-forming agents on susceptible cells.
CCl4 exerts its toxicity through its metabolites, including the free radicals CCl3. and CCl(3)00.. Oxygen strongly inhibits the hepatic cytochrome P-450-mediated formation of CCl3. from CCl4 and promotes the conversion of CCl3. to CCl(3)00.. Both these free radicals injure the hepatocyte by causing lipid peroxidation and binding covalently to cell structures. A reduced glutathione (GSH)-dependent mechanism can protect the liver microsomal membrane against CCl4-induced damage under aerobic conditions but not under anaerobic conditions (Burk, R.F., K. Patel, and J.M. Lane, 1983, Biochem. J., 215:441-445). Experiments were carried out using rat liver microsomes to examine the effect of O2 tensions found in the liver and of GSH on CCl4-induced covalent binding and lipid peroxidation. An NADPH-supplemented microsomal system was used. CCl4 or 14CCl4 was added to the sealed flask that contained the system, and after 20 min CHCl3 production, thiobarbituric acid-reactive substances (an index of lipid peroxidation), and covalent binding of 14C were measured. O2 tensions of 0, 1, 3, 5, and 21% were studied. Increases in O2 tension caused a fall in CHCl3 production, which indicated that it decreased CCl3.. GSH had no significant effect on CHCl3 production at any O2 tension. Lipid peroxidation and covalent binding of 14C fell progressively as O2 tension was increased from 1 to 21%. The addition of GSH decreased both lipid peroxidation and covalent binding, but did so better at the higher O2 tensions than at the lower ones. These results indicate that low O2 tensions such as are found in the centrilobular areas of the liver favor conversion of CCl4 to free radical products which cannot be detoxified by the GSH-dependent mechanism. They suggest that hyperbaric O2 might decrease free radical formation in the liver in vivo and promote formation of CCl(3)00. from CCl3.. This should result in diminished CCl4-induced lipid peroxidation and liver damage. Rats given CCl4 (2.5 ml/kg) were studied in metabolic chambers. Production of CHCl3 and ethane, the latter an index of lipid peroxidation, were measured. Rats in two atmospheres of 100% O2 produced much less CHCl3 and ethane than rats in air. This strongly suggests that hyperbaric O2 is decreasing free radical formation from CCl4 and/or promoting the formation of CCl(3)00. from CCl3.. These results provide the rationale for the use of hyperbaric O2 in the treatment of CCl4 ingestion.
Rat liver microsomal membranes contain a reduced-glutathione-dependent protein(s) that inhibits lipid peroxidation in the ascorbate/iron microsomal lipid peroxidation system. It appears to exert its protective effect by scavenging free radicals. The present work was carried out to assess the effect of this reduced-glutathione-dependent mechanism on carbon tetrachloride-induced microsomal injury and on carbon tetrachloride metabolism because they are known to involve free radicals. Rat liver microsomes were incubated at 37 degrees C with NADPH, EDTA and carbon tetrachloride. The addition of 1 mM-reduced glutathione (GSH) markedly inhibited lipid peroxidation and glucose 6-phosphatase inactivation and, to a lesser extent, inhibited cytochrome P-450 destruction. GSH also inhibited covalent binding of [14C]carbon tetrachloride-derived 14C to microsomal protein. These results indicate that a GSH-dependent mechanism functions to protect the microsomal membrane against free-radical injury in the carbon tetrachloride system as well as in the iron-based systems. Under anaerobic conditions, GSH had no effect on chloroform formation, carbon tetrachloride-induced destruction of cytochrome P-450 or covalent binding of [14C]carbon tetrachloride-derived 14C to microsomal protein. Thus, the GSH protective mechanism appears to be O2-dependent. This suggests that it may be specific for O2-based free radicals. This O2-dependent GSH protective mechanism may partly underlie the observed protection of hyperbaric O2 against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity.
Influenza virus added to Lettré cells at pH 5.3 induces a permeability change similar to that elicited by Sendai virus at pH 7.4: K+ and Na+ equilibrate across the plasma membrane and low-molecular-weight phosphorylated compounds leak out of cells, which remain impermeable to trypan blue.
In rat isolated lung perfused via the pulmonary circulation, 3H-TxB2 was metabolized to another radioactive species. About 60% of effluent 3H was metabolite and the same proportion of metabolite was found in lung at 5 min after the injection of 3H-TxB2. Metabolism of TxB2 was prevented by bromcresol green, dipyridamole and frusemide apparently by decreasing uptake of TxB2 by the lung. Our results support the possibility of TxB2 competing with PGE2 for metabolism in lung, although TxB2 is not a substrate for PGDH in vitro.
A patient with Stage III paratesticular neuroblastoma diagnosed in infancy was treated with radiotherapy and chemotherapy. Typical depigmented "ash leaf" skin lesions of tuberous sclerosis appeared during early childhood. At 7 years of age he underwent craniotomy for a subependymal giant cell astrocytoma. The occurrence of neuroblastoma, tuberous sclerosis, and astrocytoma is unique, and supports the suggested relationship between neural crest tumors and hamartoma syndromes.
This study seeks to explain states' adoptions of programs in health planning and in physician education. It also seeks to further understanding of the impact of federal health planning and education programs on the states. Several theories and models are employed in analyzing the actions of state decision-makers. These include incremental theory, models of the diffusion of innovations, economic resources theory, and a theory of competitive partisanship. The data utilized in this research were principally derived from intensive interviews with "key" state actors and from historical, documentary materials. Only minimal federal impact appears on states' goals in physician education and health planning. Rather, there is evidence of considerable innovativeness among the states prior to Federal program initiatives. A problem-generated search for solutions seems to be a major source of this innovation. Finally, federal program implementation requirements appear to be a major source of federal--state conflict and opposition.
The cloned HindIII fragments of human cytomegalovirus (HCMV) strain AD169 DNA were mapped with respect to the BamHI, EcoRI and PstI restriction endonuclease cleavage sites. Composite restriction endonuclease cleavage maps for the entire virus genome were constructed using the previously established linkages between the HindIII fragments.
The diffusing capacity of the lung, or transfer factor, for carbon monoxide (TLCO) was measured in 12 patients with polycythaemia rubra vera. This was significantly raised (mean 152% predicted, SEM +/- 14%) and remained so even after correction to a standard haemoglobin concentration of 14 . 6 g/dl (mean 139% predicted, SEM +/- 13%). Serial measurements of TLCO on two patients after treatment of polycythaemia rubra vera showed a greater fall in relation to haemoglobin concentration than would have been predicted on theoretical grounds if the increases in TLCO had been due entirely to the increased haemoglobin concentration. The pulmonary capillary blood volume (estimated from TLCO) also fell in these two patients after treatment. There was a strong correlation between TLCO and the technetium-99m-labelled red cell volume for the seven men (r = 0 . 92; p less than 0 . 01) and five women (r = 0 . 99; p less than 0 . 001) when studies were performed on the same day. In patients with polycythaemia rubra vera who have no evidence of coexistent pulmonary disease the pulmonary capillary bed appears to share in the expansion of the body blood volume. The single-breath TLCO test may act as a convenient and simple monitor for the response of the disease to treatment.
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During anesthetic preparation of a patient who had received routine radiation therapy for sarcoma of the leg, cardiac collapse occurred following succinylcholine (SCh) administration. Experiments were designed to test the hypothesis that radiation injury to muscle might cause increased sensitivity to SCh similar to that reported in patients with muscle trauma, severe burns, and lesions causing muscle denervation. Venous plasma potassium levels and arterial blood gas tensions were measured in rats after they were given SCh (3 mg/kg) at various times following 60Co irradiation of the hind legs. Nonirradiated rats responded to SCh with a slight but statistically significant increase in plasma K+. Rats subjected to high levels of radiation (10,000 to 20,000 R) and given SCh 4 to 7 days later responded in the same way as the control rats. Plasma K+ levels in rats exposed to a fractionated irradiated dosage (2500 R given twice with a 1-week interval) followed by SCh 1 week later were similar to those in the control group, but when SCh was given 2 weeks later (3 weeks after initial irradiation) there was a marked elevation of plasma K+, from 3.6 to 7.7 meq/L, a statistically significant increase.
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