Ping pong gaze (periodic alternating gaze): a case report.
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Accidents, Traffic↗
Biomedical subjects
M Misra
Publications and source records attributed to M Misra.
99Tcm-cystine, a renal function and imaging agent: a comparative study in dog with 131I-hippurate and 99Tcm-glucoheptonate to evaluate its functional and imaging characteristics.
99Tcm-cystine, which has been proposed as a renal radiopharmaceutical for evaluating renal morphology and function in a single experiment, is compared with 131I-orthoiodohippurate (OIH) with respect to its renal clearance and extraction parameters and with 99Tcm-glucoheptonate (GHA) regarding its imaging characteristics. In spite of its comparable renal accumulation with 131I-OIH, its clearance (10.1 +/- 1.0 ml min-1 kg-1) was lower than that of 131I-OIH (21.5 +/- 0.9 ml min-1 kg-1) but was higher than that of 125I-iothalamate (5.4 +/- 0.6 ml min-1 kg-1). Extraction efficiencies of 99Tcm-cystine, 131I-OIH and 125I-iothalamate were 39 +/- 5, 64 +/- 4 and 27 +/- 3, respectively. The glomerular filtration components of 99Tcm-cystine and 131I-OIH were 26 and 16% of their respective clearances. In probenecid-treated animals the clearance of both agents was affected to a similar extent and fell to half of their respective control values, whereas tubular secretory components were found to be 19 and 31% of the controls. The kidney images obtained with 99Tcm-cystine were superior to those obtained with 99Tcm-GHA at different time points. Therefore, considering both renal function and imaging properties of 99Tcm-cystine it appears that this radiopharmaceutical offers some definite advantages over the currently available renal agents and commands further study.
Animals↗
Expression of a cardiac Ca(2+)-release channel isoform in mammalian brain.
Mammalian brain possesses ryanodine-sensitive Ca2+ channels, which in muscle cells mediate rapid Ca2+ release from intracellular stores during excitation-contraction coupling. Analysis of bovine brain ryanodine receptor (RyR) channels suggests specific expression of the cardiac-muscle RyR isoform in mammalian brain. Localization using cardiac-muscle RyR-specific antibodies and antisense RNA revealed that brain RyRs were present in dendrites, cell bodies and terminals of rat forebrain, and highly enriched in the hippocampus. Activity of skeletal-muscle RyR channels is coupled to sarcolemmal voltage sensors, in contrast with cardiac-muscle RyR channels, which are known to be Ca(2+)-induced Ca(2+)-release channels. Thus Ca(2+)-induced Ca2+ release from intracellular stores mediated by brain RyR channels may be a major Ca(2+)-signalling pathway in specific regions of mammalian brain, and hence may play a fundamental role in neuronal Ca2+ homoeostasis.
Animals↗
Enhancement by nickel(II) and L-histidine of 2'-deoxyguanosine oxidation with hydrogen peroxide.
Conversion of the 2'-deoxyguanosine (dG) residues in calf thymus DNA to 8-hydroxy-2'-deoxyguanosine (8-OH-dG) was achieved at physiological pH by treating the DNA with hydrogen peroxide (H2O2) in the presence of nickel(II) chloride (NiCl2). The effectiveness of this reaction was enhanced by L-histidine (His) which forms the Ni(II)-His2 complex. Similar effects of NiCl2 and His were observed on hydroxylation of pure dG with H2O2. The rate of pure dG conversion to 8-OH-dG at 37 degrees C (100 mM phosphate buffer) depended on combination and concentration of the reagents and on pH. Following 24 h incubation at pH 7.4 of 0.75 mM dG with 30 mM H2O2 and 1 mM NiCl2, dG was converted into 8-OH-dG to the extent of 0.05% in the absence of His and 0.45% in the presence of 2 mM His. After 24 h incubation at pH 7.4 of 0.5 mg/ml DNA with 7.5 mM H2O2 and 0.1 mM NiCl2, 0.18% of the dG moiety was converted into 8-OH-dG in the absence of His and 0.42% in the presence of 0.2 mM His. Interestingly, a mixture of H2O2 with His was also capable of oxidizing dG to 8-OH-dG even in the absence of NiCl2, albeit less effectively than in the presence of NiCl2. This effect was not suppressed after treatment of dG, His and the buffer with Chelex to remove divalent metal contaminants, if any. The exact chemistry of the observed phenomena remains to be determined. Since the Ni(II)-His2 complex is the major low mol. wt nickel carrier in mammalian organisms, the observed redox properties of this complex, reported here for the first time, may be crucial for the toxicity and carcinogenicity of nickel.
8-Hydroxy-2'-Deoxyguanosine↗
DNA deaminating ability and genotoxicity of nitric oxide and its progenitors.
Nitric oxide (NO), a multifaceted bioregulatory agent and an environmental pollutant, can also cause genomic alterations. In vitro, NO deaminated deoxynucleosides, deoxynucleotides, and intact DNA at physiological pH. That similar DNA damage can also occur in vivo was tested by treating Salmonella typhimurium strain TA1535 with three NO-releasing compounds, including nitroglycerin. All proved mutagenic. Observed DNA sequence changes were greater than 99% C----T transitions in the hisG46 (CCC) target codon, consistent with a cytosine-deamination mechanism. Because exposure to endogenously and exogenously produced NO is extensive, this mechanism may contribute to the incidence of deamination-related genetic disease and cancer.
Codon↗
HIV-1 Rev expressed in recombinant Escherichia coli: purification, polymerization, and conformational properties.
The high-level expression of HIV-1 Rev in Escherichia coli is described. Protein in crude bacterial extracts was dissociated from bound nucleic acid with urea. A simple purification and renaturation protocol, monitored by circular dichroism, is described which results in high yields of pure protein. The purified protein binds with high affinity to the Rev-responsive element mRNA and has nativelike spectroscopic properties. The protein exhibits concentration-dependent self-association as judged by analytical ultracentrifugation and gel filtration measurements. Purified Rev showed reversible heat-induced aggregation over the temperature range 0-30 degrees C. This hydrophobic-driven and nonspecific protein association was inhibited by low concentrations of sulfate ions. Rev solutions at greater than 80 micrograms/mL, incubated at 0-4 degrees C, slowly polymerized to form long hollow fibers of 20-nm diameter. Filament formation occurs at a lower protein concentration and more rapidly in the presence of Rev-responsive mRNA. The nucleic acid containing filaments are about 8 nm in diameter and up to 0.4 micron in length. On the basis of physical properties of the purified protein, we have suggested that in the nucleus of infected cells, Rev binding to the Rev-responsive region of env mRNA may be followed by helical polymerization of the protein which results in coating of the nucleic acid. Coated nucleic acid could be protected from splicing in the nucleus and exported to the cytoplasm.
Circular Dichroism↗
Effect of organic anions on the crystallization of the Ca2(+)-ATPase of muscle sarcoplasmic reticulum.
The effect of varying the solute species on the crystallization of the Ca2(+)-ATPase from rabbit muscle reticulum (SR) is reported. We have found that substitution of KCl with salts of organic acids in the crystallization protocol reported by Pikula et al. has a profound effect on the size of two-dimensional crystalline arrays. Crystalline arrays of up to 3 microns diameter have been obtained by incubating purified calcium ATPase in standard crystallization medium but with 0.8 M sodium propionate substituted for KCl. These two-dimensional (2-D) arrays display a reduced tendency to stack in addition to having larger planar dimensions. Increasing the KCl concentration does not have the same effect on stacking or crystal growth that sodium propionate has. The production of 2-D sheets has some dependence on the hydrocarbon chain length of the salt because crystals formed in propionate were larger and less stacked than those formed in acetate or formate. There seems to be no dependence on cation. These observations suggest that in addition to reducing the forces that lead to stacking of the sheets, propionate may facilitate incorporation of the detergent-solubilized protein into the 2-D sheet.
Acetates↗
Nickel-induced renal lipid peroxidation in different strains of mice: concurrence with nickel effect on antioxidant defense systems.
Lipid peroxidation (LPO) and active oxygen-detoxifying enzymes, catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), as well as glutathione (GSH) and some related enzymes, glutathione-S-transferase (GST) and glutathione reductase (GSSG-R) were assayed in kidneys of BALB/cAnNCr (BALB/c), C3H/HeNCr-MTV- (C3H), B6C3F1, and C57BL/6NCr (C57BL) mice 3-48 h after a single intraperitoneal injection of 170 mumol nickel (II) acetate (NiAcet)/kg body wt. In control mice that received 340 mumol sodium acetate/kg, the levels of enzymes and GSH did not significantly vary in time but were different in various strains. The basal activities of CAT and SOD in in the controls were highest in BALB/c and lowest in C57BL mice (1.8:1.0 and 1.4:1.0 respectively) in contrast to that of GSH-Px which was highest in B6CF1 and lowest in BALB/c (1.3:1.0; P less than 0.05). The strain ranking of control concentrations of renal GSH was B6C3F1 greater than C3H greater than or equal to C57BL greater than BALB/c (2.8:2.4:2.3:1.0), and that of GSSG-R was C3H greater than or equal to BALB/c greater than B6C3F1 greater than or equal to C57BL [corrected] (1.5:1.4:1.1:1.0). The basal activity of renal GST in control mice was 25% lower in C3H than in any of the other 3 strains. The renal LPO levels in the control mice did not vary among strains. Nickel treatment transiently increased renal LPO levels in the control mice did not vary among strains. Nickel treatment transiently increased renal LPO in the BALB/c mice by 100%, in B6C3F1 by 30%, and in C57BL by 20% (P less than 0.05), with no significant effect in C3H mice. Thus, the magnitude of nickel-induced renal LPO was greatest in the strain that is lowest in GSH and GSH-Px, but not in CAT and SOD. Nickel effects on GSH and the enzymes were time-dependent and included transient inhibition or enhancement of different proportions with no apparent strain- and/or base level-related patterns, or concurrence with LPO. The results emphasize the importance of GSH and GSH-Px for preventing nickel-induced oxidative cell damage.
Animals↗
Nickel-induced lipid peroxidation in the liver of different strains of mice and its relation to nickel effects on antioxidant systems.
After a single intraperitoneal injection of 170 mumol nickel(II)acetate/kg body wt., the activity of hepatic catalase (CAT) decreased by 25-56% in a strain- and time-dependent manner, the most susceptible being C57BL/6NCr greater than C3H/HeNCr-MTV- greater than B6C3F1 greater than or equal to BALB/cAnNCr mice. The glutathione (GSH) levels in all 4 strains were inhibited by nickel with the C57BL/6NCr mice showing the biggest decrease (68%) followed by BALB/cAnNCr (46%) greater than or equal to B6C3F1 (42%) greater than C3H/HeNCr-MTV- (22%). The response of hepatic glutathione peroxidase (GSH-Px) to nickel was variable and included 30% enhancement in C3H/HeNCr-MTV- or lack of biologically significant effect (max. +/- 10% variations in time) in the remaining strains. The activity of glutathione reductase (GSSG-R) increased gradually by up to 30% (48 h post-injection) in B6C3F1 and C3H/HeNCr-MTV- mice or, transiently, by 15-18% (3 h), in C57BL/6NCr and BALB/cAnNCr mice. Also, in some strains, nickel significantly affected superoxide dismutase (SOD) (14-19% loss in C57BL/6NCr and B6C3F1 mice, respectively), and GSH-S-transferase (GST) (26% loss in C3H/HeNCr-MTV- mice). Lipid peroxidation (LPO) in the liver reached its highest value 24 h after nickel treatment in C57BL/6NCr (549% over the control) greater than or equal to BALB/cAnNCr (519%) greater than B6C3F1 (426%) much greater than C3H/HeNCr-MTV- (39%). In conclusion, the magnitude of nickel-induced LPO shows a reverse correlation with the extent and direction of nickel effect on GSH, GSH-Px and GSSG-R, but not on CAT, SOD or GST.
Animals↗
Effects of nickel on catalase activity in vitro and in vivo.
The decomposition of H2O2 by catalase (CAT) was measured in a cell-free in vitro system in the presence of 0-24 mM Ni(II) or Mg(II) as well as in red blood cells (RBCs), and in post-mitochondrial fractions of liver and kidney of rats injected i.p. with 95 mumol/kg of nickel acetate. In vitro, immediately after addition of Ni(II), the inhibition of the catalytic activity of CAT (at 25 degrees C and pH 7.2) was directly proportional to Ni(II) concentration while Mg(II) had no effect. Following in vivo treatment, activity of CAT in the RBCs was decreased by 12% at 16 h, but had returned to control level by 48 h post injection. Hepatic CAT activity remained unchanged during the first 24 h after the injection but subsequently decreased by 25% at 48 h. Renal CAT first increased by 17% above the control levels at 16 h, returned to the control level at 24 h, and finally decreased by 27% at 48 h post injection. These changes neither concurred with the corresponding tissue concentrations of Ni(II) nor resembled the concentration/effect relationships observed in vitro. Thus, the mechanism by which Ni(II) inhibits CAT activity in vivo is more complex than that in vitro and cannot be solely related to direct Ni(II)-CAT interaction.
Animals↗
Nickel induced lipid peroxidation in the rat: correlation with nickel effect on antioxidant defense systems.
Lipid peroxidation (LPO) and alterations in cellular systems protecting against oxidative damage were determined in the liver, kidney and skeletal muscle of male F344/NCr rats, 1 h to 3 days after a single intraperitoneal (i.p.) injection of 107 mumol nickel(II)acetate per kg body weight. At 3 h, when tissue nickel concentrations were highest, the following significant (at least, P less than 0.05) effects were observed: in kidney, increased LPO (by 43%), increased renal iron (by 24%), decreased catalase (CAT) and glutathione peroxidase (GSH-Px) activities (both by 15%), decreased glutathione (GSH) concentration (by 20%), decreased glutathione reductase (GSSG-R) activity (by 10%), and increased glutathione-S-transferase (GST) activity (by 44%); the activity of superoxide dismutase (SOD) and gamma-glutamyl transferase (GGT), as well as copper concentration, were not affected. In the liver, nickel effects included increased LPO (by 30%), decreased CAT and GSH-Px activities (both by 15%), decreased GSH level (by 33%), decreased GSSG-R activity (by 10%) and decreased GST activity (by 35%); SOD, GGT, copper, and iron remained unchanged. In muscle, nickel treatment decreased copper content (by 43%) and the SOD activity (by 30%) with no effects on other parameters. In blood, nickel had no effect on CAT and GSH-Px, but increased the activities of alanine-(ALT) and aspartate-(AST) transaminases to 330% and 240% of the background level, respectively. In conclusion, nickel treatment caused profound cell damage as indicated by increased LPO in liver and kidney and leakage of intracellular enzymes, ALT and AST to the blood. The time pattern of the resulting renal and hepatic LPO indicated a possible contribution to its magnitude from an increased concentration of nickel and concurrent inhibition of CAT, GSH-Px and GSSG-R, but not from increased iron or copper levels. The oxidative damage expressed as LPO was highest in the kidney and lowest in the muscle, which concurs with the corresponding ranking of nickel uptake by these tissues.
Alanine Transaminase↗
Initiation by nickel acetate and promotion by sodium barbital of renal cortical epithelial tumors in male F344 rats.
Soluble nickel(II) ion, given to male F344/NCr rats as a single i.p. injection of nickel(II) acetate tetrahydrate at a dose of 90 mumols/kg body weight at 5 weeks of age, proved an effective initiator of renal cortical epithelial tumors. The tumors were revealed by subsequent dosing with the known renal tumor promoter, sodium barbital (5,5-diethylbarbituric acid, sodium salt) dissolved in drinking water at a concentration of 500 p.p.m. Only one rat given the nickel injection without subsequent promotion developed a single renal cortical adenoma, while multiple tumors were common in nickel(II) initiated/sodium barbital promoted rats. Renal cortical adenocarcinomas, some of them metastatic to lung, liver, and spleen, occurred only in initiated/promoted rats. No excess incidence of nickel-initiated tumors was found in any other tissues in which sodium barbital is known to promote carcinogenesis, such as liver or thyroid. A single i.p. injection of the Ni(II) salt, 95 mumols/kg, appeared to be associated with an increased concentration of 8-hydroxy-2'-deoxyguanosine in DNA extracted from kidneys of rats 16-48 h after injection.
Acetates↗
The ryanodine receptor-Ca2+ release channel complex of skeletal muscle sarcoplasmic reticulum. Evidence for a cooperatively coupled, negatively charged homotetramer.
The subunit structure of the rabbit skeletal muscle ryanodine receptor-Ca2+ release channel complex was examined following solubilization of heavy sarcoplasmic reticulum membranes in two zwitterionic detergents, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (Chaps) and Zwittergent 3-14. High and low affinity [3H]ryanodine binding was retained upon solubilization of the complex in Chaps but was lost in Zwittergent 3-14. The purified complex migrated as a single peak with an apparent sedimentation coefficient of approximately 30 and approximately 9 S upon density gradient centrifugation and with isoelectric points of 3.7 and 3.9 upon two-dimensional gel electrophoresis in Chaps and Zwittergent 3-14, respectively. Electron microscopy of negatively stained samples indicated that the distinct four-leaf clover structure of the ryanodine receptor observed in Chaps disappeared following Zwittergent treatment of the 30 S complex and instead showed smaller, round particles. Ferguson plot analysis following sodium dodecyl sulfate-polyacrylamide gel electrophoresis of partial and fully cross-linked and incompletely denatured complexes suggested a stoichiometry of four Mr approximately 400,000 peptides/30 S ryanodine receptor oligomer. [3H]Ryanodine binding to the membrane-bound receptor in 50 microM--1 mM free Ca2+ revealed the presence of both high affinity (KD = 8 nM, Hill coefficient (nH) = 0.9) and low affinity (nH approximately 0.45) sites with a ratio of 1:3. Reduction in free Ca2+ to less than or equal to 0.1 microM or trypsin digestion of the membranes resulted in loss of high affinity but not low affinity ryanodine binding (Hill KD = 5,000 nM, nH = 0.9). Addition of 20 mM caffeine to the nanomolar Ca2+ medium decreased the Hill KD to 1,000 nM without changing the Hill coefficient. Occupation of the low affinity sites altered the rate of [3H]ryanodine dissociation from the high affinity sites. Single channel recordings of the purified ryanodine receptor channel incorporated into planar lipid bilayers also indicated the existence of high and low affinity sites for ryanodine, occupation of which resulted in formation of a subconducting and completely closed state of the channel, respectively. These results are compatible with a subunit structural model of the 30 S ryanodine receptor-Ca2+ release channel complex which comprises a homotetramer of negatively charged and allosterically coupled polypeptides of Mr approximately 400,000.
Animals↗
Failure of oral atenolol and verapamil to increase the capacity and duration of exercise in patients in sinus rhythm with mitral stenosis.
The efficacy of oral atenolol in increasing the capacity and duration of exercise in 43 patients in sinus rhythm with mitral stenosis was evaluated and compared with that of oral verapamil in an open-label cross-over design. It was observed that although oral atenolol (100 mg per day) caused significant reductions in heart rate while resting and during exercise (P less than 0.001), the increases in capacity and duration of exercise were not significant. Oral verapamil (80 mg three times per day) also caused significant reductions in the heart rates at rest and during exercise (P less than 0.05) but the increases observed, although greater than that with atenolol, failed to reach the level of statistical significance. Occasional side effects occurred with both the drugs. Subjective symptoms of dyspnoea at rest and on exertion were relieved with both the drugs. We conclude that, although both drugs reduce the symptoms of dyspnoea, they cause only minor increases in the objective parameters. They do not, therefore, provide an alternative to surgery and have only a temporary place in the management of patients in sinus rhythm with mitral stenosis who are awaiting surgery.
Administration, Oral↗
Biodistribution of two 99mTc-cardiac glycosides with end glucose unit: effect of lipophilicity on their relative myocardial accumulation.
In biodistribution experiments with tritium labelled cardiac glycoside it was observed that compounds of low lipophilicity showed a considerably higher affinity towards myocardium with respect to other tissues and organs. A similar trend was also observed with 99mTc-cardiac glycosides except for one compound with glucose residue, which in spite of its lower lipophilicity exhibited an unexpectedly low heart to non-target concentration ratio, thereby indicating a possible influence of carbohydrate residue on biodistribution. To confirm this, in this article we radiolabelled two glucose containing cardiac glycosides (K-strophanthin-beta and K-strophanthoside) with 99mTc and, in biodistribution experiments, less lipophilic 99mTc-K-strophanthoside showed a much better heart to non-target ratio over 99mTc-K-strophanthin-beta. It is thus concluded that, in addition to lipophilicity, the affinity of the carbohydrate residue for non-target organs is also an important consideration in determining the structure-distribution relationship of 99mTc-cardiac glycosides.
Animals↗
Acute inflammatory demyelinating polyradiculoneuropathy presenting as complete heart block and Stoke-Adams attacks.
A patient with acute inflammatory demyelinating polyradiculoneuropathy (AIDP, Guillain-Barré syndrome) whose presenting complaints were related to autonomic dysfunction in the form of parasympathetic and sympathetic overactivity is reported. Parasympathetic overactivity was severe enough to cause complete atrioventricular block (atropine-responsive) and Stoke-Adams attacks, for which a demand pacemaker was required. Limb weakness was apparent 48 hours later. To our knowledge no such presentation of AIDP has been previously recorded.
Acute Disease↗
Comparative effects of chelating drugs on trace metal and biochemical alterations in the rat.
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Animals↗
Alleviation of nickel-induced biochemical alterations by chelating agents.
The effect of 1,4,8,11-tetraazacyclotetradecane (Cyclam), triethylenetetramine (TETA), reduced glutathione (GSH), ethylenediamine tetraacetic acid (EDTA), cyclohexanediamine tetraacetic acid (CDTA), diethylene triamine pentaacetic acid (DTPA), and hydroxyethylenediamine triacetic acid (HEDTA) on the alleviation of nickel-induced biochemical and trace-metal alterations in serum, liver, and kidney of nickel-treated rats was studied. The lipophilic chelating agents Cyclam and TETA exhibited a higher order of effectiveness in alleviating nickel-induced alterations compared to EDTA, CDTA, DTPA, and HEDTA, the hydrophilic chelating agents. The higher efficacy of lipophilic agents may be due to their ability to bind to nickel present in extracellular fluid as well as in intracellular fluid, while the hydrophilic agents may bind only to nickel present in extracellular fluid. Our data also suggest that the efficacy of Cyclam to ameliorate nickel-induced alterations is exceptionally high.
Alanine Transaminase↗