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Biomedical subjects

J L Rabinowitz

Publications and source records attributed to J L Rabinowitz.

At least 55 records · Page 3Linked to original sources

[Labelled CO2 breath-tests in gastroenterology (author's transl)].

The use of a few microcuries of 14C labelled molecules with very short biological half-life for breath-tests gives no more body irradiation than 10 minutes' exposure to the sun. Yet it provides the gastroenterologist with accurate information. Detection and identification of fat malabsorption are easy when 3 labelled lipids are used. Glycine 1 14C cholate administered orally offers a simple, rapid and effective screening technique for the detection of increased bile salt deconjugation and may provide a valuable diagnostic supplement in the study of steatorrhea after ileal resection, bypass or bacterial overgrowth. The clearance of labelled aminopyrine can be decreased in hepatocellular dysfunction or increased in some alcoholic patients or in patients receiving phenobarbitone. Tracer doses of labelled ethanol were used to study the metabolism of ethanol by the liver in alcoholic patients. Chronic ingestion of alcohol stimulates the activity of microsomal drug-metabolising enzymes in both non-cirrhotic and cirrhotic patients; this response is lost in acute liver damage and in chronic alcoholic disease with severe hepatic dysfunction. The CO2-labelled breath-tests are non-invasive, effective and inexpensive. The forthcoming replacement of 14C by non-radioactive 13C or briefly radioactive 11C will render these tests even more attractive.

Adult↗

14CO2 in breath.

The diagnosis of metabolic disorders can be made by detecting 14CO2 in the breath. This is possible because 14CO2 can label any organic compound without any deteriorations in the nature of the compound. This type of analysis is dependable, noninvasive and simple to perform with a scintillation counter.

Aminopyrine↗

Fatty acid metabolism in human fetal placental vasculature.

The utilization of exogenous acetate and palmitate for the synthesis of vascular wall lipids was studied in isolated blood vessels of the human placenta under high- and low-oxygen conditions. Arteries and veins were obtained from fresh placental material and incubated in Krebs-Henseleit buffer (pH 7.4 at 37 degrees C) containing (in mM) either [2-14C]acetate, 0.11; [1-14C]palmitate, 0.43; or [16-14C]palmitate, 0.43. At the end of the 180-min incubation, neutral lipids accounted for 40%, and phospholipids 60%, of the 14C recovered. Following incubation with either precursor, 14C label was recovered mainly in 16-carbon fatty acids (FA) (35%) and 18-carbon FA (45%); less than 10% was recovered in less than or equal to 14-carbon FA and greater than or equal to 20-carbon FA. Estimates of synthesis rate however indicated that the 18- and 20-carbon FA had the highest turnover rates. Schmidt degradation analysis demonstrated considerable labeling of alkyl carbons after incubation with either carboxyl- or alkyl-labeled precursors, indicating that FA degradation products were used for de novo FA synthesis. Collectively, these findings suggest the presence of both de novo and chain elongation pathways. No differences were observed between arteries and veins, and anoxia had little influence on FA metabolism. Analysis of ATP levels demonstrated elevated concentrations of ATP present, accounting for the apparent lack of anoxic inhibition of FA metabolism.

Acetates↗

Reutilization of fatty acid carbons for lung lipid synthesis.

The utilization of glucose, palmitate, and oleate for the synthesis of lung lipids was studied in isolated rat lungs. Lungs were ventilated with 5% CO2 in air and perfused for 100 min with a Krebs-Ringer bicarbonate buffer (pH 7.4), containing 3% fatty acid-free albumin and either 5.6 mM [U-14C]glucose or 0.25 mM [1-14C]palmitate, or 0.25 mM [1-14C]-oleate. At the end of 100 min of perfusion with these precursors, between 73 and 85% of total lipid 14C was recovered as phospholipid. Glucose carbon was mainly incorporated into triglyceride fatty acids (TG-FA) and phosphatidylcholine fatty acids (PC-FA) of 16- and 18-carbon chain length. After perfusion with [14C]palmitate and [14C]oleate, only 65 and 20% of 14C was recovered as PC 16-carbon and 18-carbon FA, respectively. The remaining 14C was mainly recovered as FA shorter than the 14C precursors. Schmidt degradation analysis of lipid FA demonstrated considerable labeling of alkyl carbons on perfusion with the carboxyl-labeled precursors, indicating that FA degradation products were used for synthesis of lipid FA. This process was enhanced on addition of glucose to the perfusate.

Animals↗

Pathways of palmitate metabolism in the isolated rat lung.

Plasma fatty acids represent major precursors of lung lipids. In this study, the pathways of palmitate metabolism were measured in an isolated perfused rat lung. Lungs were ventilated with 5% CO2 in air and perfused with Krebs-Ringer bicarbonate containing 3% serum albumin and 0.25 mM [U-14C] and [9, 10(-3)H] palmitate. Fatty acid utilization was estimated by recovery of radiolabel in products of metabolism. Fourteen percent of a total 14C-fatty-acid utilization of 4.5 mumol fatty acid/100 min/g dry wt. was recovered as 14CO2. Degradation of fatty acid to acetyl CoA was indicated by a 3H2O production that was twice fatty acid oxidation to CO2. The majority of palmitate was recovered in lung phosphatidylcholines with a 14C to 3H ratio of 1.4 accounting for differences between 14C and 3H2O productions. Addition of glucose to the perfusate decreased fatty acid oxidation to CO2 by 32% but had no effect on 14C recovery in phospholipids. Perfusion with the uncoupler of oxidative phosphorylation 2,4-dinitrophenol stimulated fatty acid oxidation twofold but decreased 14C incorporation into lipids. These data together with estimates of fatty acid synthesis based on 3H2O incorporation into lipids, suggested that exogenous fatty acids and glucose both represent sources of carbon for de novo fatty acid synthesis and energy production.

Animals↗

A bitewing radiographic study of a population of diabetic and nondiabetic rhesus monkeys.

A population of 7 diabetic and 13 nondiabetic rhesus monkeys (Macacca mulatta) were examined radiographically using bitewing imaging techniques. Each subject was scored radiographically for bone levels, periodontal ligament (PDL) widening, radiographic calculus, and carious lesions. Prior to examinations blood samples were obtained for fasting blood glucose levels. Results indicated that all clinical variables were generally greater for the diabetic group, with bone loss being the only statistically significant parameter. Calculus levels, however, were found to be greater radiographically in the nondiabetic group. In viewing the study population as a single group of 20 monkeys, decreased bone levels were found to be positively correlated with PDL widening and blood glucose levels suggesting an association of hyperglycemic states with possible decreased resistance to infection. It was concluded that carbohydrate intolerance with hyperglycemia in diabetes mellitus may be associated with the radiographic variable of increased bone resorption using an objective system of measurement for evaluation and scoring. Without a quantitative system of measurement such as devised in this study, other radiographic variables such as PDL widening, calculus deposits, and carious lesions may not be accurately tested against one another or correlated with other experimental clinical parameters.

Alveolar Process↗

[Hyperoctanoatemia and the hepatic encephalopathy of cirrhosis. 150 dosages in 61 patients (author's transl)].

A new and sensitive method for determination of octanoate in serum by gas-liquid chromatography is described. It was validated by mass spectrometry. Octanoate concentrations were determined in the serum of 61 fasting cirrhotic patients of which 47 also had hepatic encephalopathy. Concentrations in arterial and venous blood were higher in cirrhotic patients with encephalopathy than in those without and higher in the latter than in controls. Arterial concentrations were higher than venous concentrations and octanoate and ammonia varied independently. A predominant endogenous origin is likely. Data obtained from studies using palmitic acid labeled at different loci suggest that recovered serum octanoate was formed mostly by incomplete oxidation of long chain fatty acids. Sodium octanoate infusion to rhesus monkeys studied polygraphically induces a temporary coma.

Adult↗

Isolation and characterization of the erythrocyte surface membrane of the smooth dogfish, Mustelus canis.

1. The plasma membrane of the dogfish erythrocyte is characterized. 2. Surface membranes were isolated from dogfish red cells. 3. Cells suspended in a hypotonic zinc chloride buffer (0.5 mM ZnCl2, 5 mM Tris-HCl, pH 8.0) tended to enucleate spontaneously. 4. By gentle homogenization relatively high yields of red cell "ghosts" were formed; these were purified using discontinuous gradients of sucrose and of glycerol solutions. Analyses of protein, carbohydrates and lipids were carried out. 5. There did not appear to be marked overall differences in the composition of the surface membrane of the nucleated dogfish erythrocyte compared to those of other species.

Amino Acids↗

Lipid composition of the tissues of human knee joints. I. Observations in normal joints (articular cartilage, meniscus, ligaments, synovial fluid, synovium, intra-articular fat pad and bone marrow).

The composition and lipid profiles of the following tissues of the human knee joint were determined: articular cartilage, meniscus, ligaments, synovial fluid, synovium, intra-articular fat pad and bone marrow. The tissues were obtained from fresh cadavers and from surgical specimens. The lipid profiles of articular cartilage, meniscus and ligaments were similar to reported analyses of other tissues that are also rich in collagen. The lipid profiles for the remaining tissues were more like the profiles found in the fat depots and fatty tissues of the human body. Both the phospholipid and fatty acid patterns of these tissues were similar within statistical deviation. These results suggest that the per cent compositions of fatty acids and the phospholipid family profile ratios have limited range variability in the "normal" tissues of the human knee. On the other hand, the per cent neutral lipid compositions and their individual profiles showed great variations among the different tissue tissues of the knee.

Adipose Tissue↗

Preliminary characterization of the delta-9 desaturase of Tetrahymena pyriformis W.

1. In vitro assay conditions have been defined for measurement of delta 9 desaturase activity in Tetrahymena pyriformis W. 2. The reaction depends on the presence of oxygen and a reduced pyridine nucleotide cofactor. FAD supports a low level of enzymatic activity. 3. Both stearyl-CoA and palmityl-CoA are acceptable substrates. Oleate formation is maximal at 30 degrees C. 4. Delta-9 desaturase activity appears to be localized in the microsomal fraction. Delta-6 and/or delta 12 desaturase activities have also been observed. 5. When the specificity of the delta 9 desaturase towards stearyl-CoA and palmityl-CoA was observed at 30 and 16 degrees C it was found that lowering the assay temperature did not affect specificity. Stearyl-CoA was more readily desaturated at both temperatures. 6. Exogenous oleyl-CoA and diisopropylfluorophosphate had little effect on delta 9 desaturase activity. However, cyanide strongly inhibited desaturation and a sensitivity to sulfhydryl-binding reagents has also been demonstrated.

Animals↗

Sources of serum [14C]-octanoate in cirrhosis of the liver and hepatic encephalopathy.

Serum octanoate levels of patients with liver cirrhosis and hepatic encephalopathy have been shown to be three to 15 times higher than those of controls. Assays for octanoate have been modified to permit isolation of pure octanoate after GLC. Patients with these conditions were given intravenously differently labeled [14C]-palmitates; serum [14C]-octanoate was isolated in each case and shown by mass spectrometry to be authentic octanoate. [1-14C]-oleate and [1-14C]-stereate were also shown to serve as precursors of serum [14C]-octanoate. When differently labeled palmitates (1-[14C]; omega [14C]; and [14C]-uniformly labeled) were used, different yields of serum [14C]-octanoate were recovered. Octanoate samples were chemically degraded to yield individual carbons or groups of carbons. In this manner it was possible to determine the percentage distribution of the [14C] label within the octanoate carbon chain. The data obtained from these studies suggest that 60% to 80% of the serum octanoate was obtained from the incomplete beta-oxidation of long-chain fatty acids and that 20% to 40% of the octanoate may have been formed de novo.

Caprylates↗