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Biomedical subjects

L Levy

Publications and source records attributed to L Levy.

At least 109 records · Page 6Linked to original sources

Acute ethanol ingestion raises plasma gamma amino-butyric acid levels in healthy men.

The effect of acute ethanol ingestion on plasma gamma aminobutyric acid (GABA) levels was investigated in eight volunteers. Subjects were studied on two days: a control during which light activity and non-alcoholic fluid intake was allowed and a study day during which ethanol was ingested to maintain blood alcohol levels at a mean of 130 mg%. Plasma GABA levels were estimated at 1, 4 and 8 hr. GABA levels were raised at 1 and 4 hr on the study day compared to the control day. GABA levels at 8 hr were not significantly different on the two days. Acute alcohol ingestion raised plasma GABA in healthy male volunteers.

Adult↗

Flecainide acetate for conversion of acute supraventricular tachycardia to sinus rhythm.

The efficacy of intravenous flecainide acetate (maximum 2 mg/kg or 150 mg given at a rate of 15 mg/min) was assessed in patients with acute supraventricular tachycardia (SVT) (within 24 hours). Fifty patients were studied, 46 with spontaneous SVT and 4 with induced SVT at electrophysiologic assessment. Conversion to sinus rhythm was achieved within 45 minutes in 76%: in 25 patients with atrial fibrillation (76% conversion), 15 with atrioventricular (AV) nodal or AV reentrant tachycardia (100% conversion) and 10 with atrial flutter or atrial reentrant tachycardia (40% conversion). Adverse effects were noted in 21 patients (42%): paresthesia in 9, drowsiness in 8, nausea in 2, accelerated ventricular rate in 5, ventricular tachycardia in 1, sinus bradycardia in 1 and hypotension in 5. Adverse effects were associated with larger dosage and atrial flutter or atrial reentrant tachycardia. Thus, flecainide acetate is effective in converting to sinus rhythm acute atrial fibrillation and AV nodal and AV reentrant tachycardias, but not atrial flutter or atrial reentrant tachycardia.

Acute Disease↗

Characterization of equine infectious anemia virus long terminal repeat.

The long terminal repeats (LTRs) of equine infectious anemia virus (EIAV) were examined with respect to their ability to function as transcriptional promoters in various cellular environments. Nucleotide sequence analyses of the LTRs derived from two unique proviral clones revealed the requisite consensus transcription and processing signals. One of the proviruses possessed a duplication of a 16-base-pair sequence in the CCAAT box region of the LTR which was absent in the other provirus. To assess its functional activity, each LTR was coupled to the bacterial chloramphenicol acetyltransferase gene and transfected onto various cell lines, including matched cultures of EIAV-infected and uninfected cells. The levels of chloramphenicol acetyltransferase activity directed by the EIAV LTRs were between 250 and 900 times greater in EIAV-infected cells compared with their uninfected counterparts. Thus, EIAV expression appears to be activated by a virus-induced trans-activation phenomenon analogous to that recently shown to amplify expression of certain other lentiviruses.

Base Sequence↗

Elevation in cytosolic free calcium concentration early in myocardial ischemia in perfused rat heart.

Changes in cytosolic free calcium concentration during myocardial ischemia were measured by 19F NMR in 5FBAPTA-loaded perfused rat hearts. The hearts were perfused with Krebs-Henseleit buffer containing 5 microM of the acetoxymethyl ester of 5FBAPTA, which was hydrolyzed by cytosolic esterases to achieve cytosolic concentrations of 5FBAPTA of 0.12 to 0.65 mM. Cytosolic free calcium concentrations were calculated as the product of the ratio of peak areas for bound and free 5FBAPTA in the NMR spectra and the dissociation constant (708 nM). The basal cytosolic calcium concentration, measured in potassium or magnesium arrested hearts, was 252 nM, and the time-average calcium concentration in beating hearts was 630 nM. Following the onset of total ischemia, there was no immediate substantial change in cytosolic calcium despite a rapid decline in creatine phosphate and ATP and a marked increase in inorganic phosphate as monitored by 31P NMR, but by 10 minutes, there was a substantial increase in free calcium concentration. The ratio of peak areas of bound and free 5FBAPTA returned to the preischemic value during reperfusion, and there was no detectable loss of 5FBAPTA from the heart. Creatine phosphate was also restored to its preischemic level during reperfusion. These results indicate that cytosolic free calcium increases during ischemia and is not immediately associated with lethal injury. This increase in cytosolic calcium may activate degradative enzymes that eventually could compromise myocyte viability.

Animals↗

Cytosolic free calcium levels in sickle red blood cells.

In this study, we used a recently developed nuclear magnetic resonance (NMR) technique to measure ionized calcium in sickle erythrocytes. The NMR technique, which involves 19F NMR studies of a fluorinated calcium chelator quinMF, [2-(2-amino-4-methyl-5-fluorophenoxy)methyl-8-aminoquinoline-N,N,N',N'- tetraacetic acid] provides a novel approach to the study of ionized calcium in erythrocytes since the presence of hemoglobin precludes the use of fluorescent calcium indicators. The mean value for ionized calcium in oxygenated sickle erythrocytes was 18 +/- 2 nmol/L (SE). Experiments with normal RBCs gave a mean value of 21 +/- 2 nmol/L (SE). After 1 hour of deoxygenation, mean values for ionized calcium in sickle erythrocytes did not increase as compared with values obtained under oxygen. To investigate whether deoxygenation stimulated endocytosis, sickle erythrocytes were deoxygenated for 1 hour in the presence of impermeant FBAPTA (1,2 bis-(2-amino-5-fluorophenoxy) ethane N,N,N',N'-tetraacetic acid). Cells were then separated from the extracellular medium and assayed for the presence of FBAPTA; they had incorporated significant quantities of the extracellular FBAPTA. This incorporation was not observed with normal erythrocytes. These data are consistent with at least a portion of the elevation in total cell calcium in sickle erythrocytes arising as a consequence of an endocytotic process in which extracellular calcium ions are incorporated into vesicles. Additional experiments show that these intracellular vesicles accumulate Ca2+ on further deoxygenation, consistent with a transient increase in ionized cell calcium. These studies represent the first use of NMR spectroscopy to evaluate endocytotic processes.

Aminoquinolines↗

Biochemically damaged erythroblasts bind natural serum antibodies and activate complement.

Friend leukaemia erythroblasts which had been damaged biochemically by treatment with inhibitors of cellular metabolism (sodium fluoride, sodium azide) or of protein synthesis (cycloheximide, puromycin) were incubated with heat-inactivated or fresh mouse serum and tested for surface-bound IgG and C3c, respectively, by reaction with FITC-immunoconjugates followed by flow-cytofluorometry. Erythroblasts exposed to sodium azide, cycloheximide or puromycin showed specific binding of IgG; the extent of binding was related to the concentration of the drugs and duration of treatment. Moreover, prolonged exposure of the cells to the inhibitors of protein synthesis lead to a dose-dependent activation of complement. The results suggest that the opsonization of biochemically-damaged Friend leukaemia erythroblasts with IgG and C3 may facilitate their interaction with macrophages.

Antibodies, Anti-Idiotypic↗

The capacity of macrophages from different murine tissues to metabolise ethanol and generate an ethanol-dependent non-dialysable cytotoxic activity in vitro.

Tissue macrophages obtained from liver, bone marrow, spleen and thymus of C57 BL/6 mice closely resembled blood-monocyte-derived human macrophages in three characteristics. These were: the rate of metabolism of ethanol to acetate, the biochemical pathways involved in ethanol metabolism and the ability to generate an ethanol-dependent non-dialysable cytotoxic activity in vitro. The metabolism of ethanol by all four types of murine tissue macrophage was only slightly suppressed by pyrazole, 4-iodopyrazole and 3-amino-1,2,4-triazole, which are known to inhibit alcohol dehydrogenase (ADH), pi ADH and catalase respectively. By contrast, ethanol metabolism by these cells was strongly suppressed by three inhibitors of the cytochrome P-450-dependent microsomal ethanol-oxidising system--namely, carbon monoxide, metyrapone and tetrahydrofurane.

Acetates↗

Strokes among black people in Harare, Zimbabwe: results of computed tomography and associated risk factors.

Computed tomography was performed and risk factors evaluated in 100 consecutive adult patients presenting to the two teaching hospitals in Harare with a clinical diagnosis of stroke. The mean age of the patients was 52; only 28 were 65 or older. Non-stroke lesions were found in seven patients and were predicted by a recent history of convulsions (p less than 0.0001). Five lesions (four subdural haematomas and one cerebral cysticercosis) were remediable. Hypertension was present in 27 (93%) of the 29 patients with cerebral haemorrhage and in 49 (53%) of the 93 patients with stroke lesions. In 22 (45%) of these patients the hypertension had not been diagnosed, and another 22 had defaulted from treatment. All 13 patients who died before computed tomography had hypertension, and over half showed evidence of haemorrhagic stroke. There was a cardiac source for all 12 cases of cerebral embolism. In eight of the 100 patients cerebral infarction was attributed to neurosyphilis. None of the patients had clinical evidence of atherosclerosis. Smoking and oral contraceptives did not seem important risk factors for stroke. Detection and control of hypertension remain the most important measures needed to reduce the incidence of and mortality from stroke in Zimbabwe.

Aged↗

In vitro reversibility of cadmium-induced inhibition of phagocytosis.

Cadmium chloride, administered chronically in the drinking water of CBA/H mice, produced a delayed clearance of particles and soluble material bearing Fc fragments (D. W. Knutson, D. L. Vredevoe, K. R. Aoki, and L. Levy, 1980, Immunology, 40, 17-26; D. L. Vredevoe, L. Levy, D. Knutson, G. Cook, and P. Cohen, 1985, Environ. Res. 37, 373-382). The inhibition was reversed upon removal of the cadmium from the water, even though a tissue load of cadmium persisted. An in vitro system was developed to analyze the mechanism of the inhibition. Binding and ingestion of sheep red blood cells (E) treated with IgG (for measurement of Fc receptor activity) or IgM and complement (C) (for measurement of complement receptor activity) were studied in resident and elicited murine peritoneal macrophages in vitro. Elicited macrophages provided the most definitive test system. With this system, there was significant inhibition of ingestion of E-IgG and E-IgMC. Binding of both types of erythrocytes was not inhibited, except at the highest concentration (10(-4) M) of CdCl2 at which binding of only E-IgMC was affected. These effects were reversible upon removal of cadmium. Migration of Fc and C receptors on the macrophage surface was not significantly affected by cadmium. In general, cadmium did not alter the expression or the binding of Fc or C receptors on macrophages. The mechanism for delayed clearance appears to be due to inhibited internalization of the particles. This is consistent with the interpretation that cadmium is a membrane active agent.

Animals↗

Prognostic factors associated with patient survival during nutritional rehabilitation in malnourished children and adolescents with cystic fibrosis.

Nineteen children and adolescents with cystic fibrosis and malnutrition were given intensive nutritional support in an effort to reverse malnutrition. Standard techniques of enteral and parenteral feeding were used. As 10 of 19 patients died shortly after nutritional intervention began, we retrospectively analyzed patient data in order to discover whether or not any patient characteristics were associated with survival. Using a multivariate analysis, a linear discriminant function was derived employing average heart rate, the presence or absence of Pseudomonas cepacia in the sputum culture, PaCO2, and the patient's age at the time of intervention. This function correctly classified these 19 patients. A further 10 nonselected CF patients who also received nutritional support were similarly assessed using the function, and again, survival was accurately predicted. Therefore, this function can be used to predict the likelihood of patient survival during the provision of advanced nutritional support. It may be helpful in deciding whether or not advanced nutritional support is warranted in certain CF patients.

Adolescent↗

Nuclear magnetic resonance measurement of cytosolic free calcium levels in human red blood cells.

Red blood cells were loaded with 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (FBAPTA) by incubation with 50 microM of the acetoxymethyl ester (FBAPTA-AM), and cytosolic free Ca2+ was monitored with 19F-nuclear magnetic resonance (NMR). Loading with 50 microM FBAPTA-AM, which results in a final FBAPTA level of approximately 0.5 mM, caused only a 25-30% fall in cell ATP as measured by 31P-NMR when 5 mM pyruvate was present. Leakage of the NMR active Ca2+ indicator, which results from cell lysis, was corrected for with the addition of extracellular Eu3+ ions, extracellular ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA), or washing. With this method, we have found basal levels of cytosolic free Ca2+ averaging 61 +/- 6 nM (means +/- SE, n = 19). When the intracellular level of FBAPTA was varied from 0.1 to 1.0 mM, there was no correlation between the level of cytosolic free Ca2+ and the level of loading with FBAPTA. Addition of 10 microM of the Ca2+ ionophore A23187 with extracellular Ca2+ set at different levels by Ca2+-EGTA buffers caused an increase in cytosolic free Ca2+ as expected. Furthermore, ATP depletion caused a two- to three-fold increase in cytosolic free Ca2+, consistent with inhibition of Ca2+ efflux via that Ca2+-ATPase.

Adenosine Triphosphate↗