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Biomedical subjects

M Kaplan

Publications and source records attributed to M Kaplan.

At least 19 recordsLinked to original sources
PubMed1992

[Increased propensity to oxidation of LDL of hypertensives].

Increased incidence of atherosclerosis has been noted in hypertension, but prevention of ischemic heart disease has not been achieved. We studied the propensity to oxidation of LDL obtained from 15 nonsmoking hypertensives (mean age 51 +/- 10) before drug therapy, and compared the results with those of LDL obtained from a similar group of normotensive controls. After oxidation with copper ions (10 microM) there was substantially increased oxidation of LDL derived from the hypertensives in comparison to that of the controls. The mean values (nmol/mg protein +/- SD; n = 15) were: malondialdehyde 55 +/- 11, peroxides 224 +/- 52, and conjugated dienes 250 +/- 56, compared to values of 26 +/- 5, 123 +/- 31 and 175 +/- 44, respectively, in the control group (p less than 0.01). It is concluded that the increased propensity of LDL to oxidation in hypertension may be the link to atherosclerosis.

Adult↗
PubMed1992

Effect of one-legged exercise on the strength, power and endurance of the contralateral leg. A randomized, controlled study using isometric and concentric isokinetic training.

The purpose of this investigation was to study the effect of one-legged exercise on the strength, power and endurance of the contralateral leg. The performance of the knee extensor and flexor muscle of 20 healthy young adults (10 men and 10 women) was first tested by Cybex II+ and 340 dynamometers. Then 10 subjects were chosen at random to train using one leg three times a week for 7 weeks whilst the other 10 served as controls. During the 8th week, the tests were repeated. Both quadriceps and hamstring muscles of the trained subjects showed a cross-transfer effect from the trained limb to the untrained side. This concerned the strength and power, as well as endurance characteristics of these muscles. The average change in peak torque of the quadriceps muscle was +19% (P less than 0.001) in the trained limb, +11% (P less than 0.01) in the untrained limb and 0% in the control limbs. In hamstring muscles the changes were +14% (P less than 0.01), +5% and -1%, respectively. Concerning muscle endurance (work performed during the last 5 contractions in the 25-repetition test) the corresponding changes were +15% (P less than 0.01), +7% (P less than 0.01), and -1% in quadriceps muscle, and +17% (P less than 0.05), +7%, and -3% in hamstring muscles. The average strength benefit in the untrained limb was +36% (hamstring muscles) and +58% (quadriceps muscle) of that achieved in the trained limb. Untrained hamstring muscle showed better benefits in the endurance parameters than in strength or power parameters, while in the quadriceps muscle this effect was reversed. A positive relationship was observed between the changes (greater improvement in the trained limb resulted in greater improvement in the untrained limb) (hamstring muscles: r = 0.83, P less than 0.001, quadriceps muscle: r = 0.53, P less than 0.001). In endurance parameters, this relationship was almost linear while in the strength and power parameters the results were more in favour of a curvilinear relationship with limited benefit.

Adult↗
PubMed1992

Apolipoprotein E and lipoprotein lipase reduce macrophage degradation of oxidized very-low-density lipoprotein (VLDL), but increase cellular degradation of native VLDL.

Oxidized low-density lipoprotein (Ox-LDL) has been shown to be taken up by the macrophage-scavenger receptor at an enhanced rate in comparison to native LDL, with consequent cellular cholesterol accumulation. In the present study, we analyzed macrophage interaction with very-low-density lipoprotein (VLDL) from normolipidemic subjects (N-VLDL) that was oxidized in the presence of 10 mumol/L copper ions. Oxidized VLDL (Ox-VLDL) contained increased conjugated dienes and malondialdehyde (MDA) equivalents and showed increased electrophoretic mobility. Gradual fragmentation of VLDL apolipoproteins (apo) was noted, with apo B-100 being the first to be fragmented, followed by apo E and apo C. Degradation of Ox-VLDL by mouse peritoneal macrophages (MPM) was increased almost twofold in comparison to N-VLDL. Upon incubation of VLDL with lipoprotein lipase (LPL), the LPL-treated lipoprotein demonstrated up to 50% increased degradation by macrophages in comparison to control N-VLDL. However, the degradation of LPL-treated Ox-VLDL was decreased by up to 20% in comparison to control Ox-VLDL. Similarly, the addition of apo E to VLDL enhanced its cellular degradation by 56%, whereas a 20% reduction in the degradation of apo E-treated Ox-VLDL was demonstrated in comparison to nontreated Ox-VLDL. These results showed that LPL and apo E, two important regulatory substances in cellular metabolism of plasma lipoproteins, increased macrophage degradation of native VLDL, but reduced the degradation of Ox-VLDL. These inhibitory effects on macrophage uptake of Ox-VLDL suggest that apo E and LPL may possess antiatherogenic potential.

Animals↗
PubMed1992

Management of neonatal Graves disease with iopanoic acid.

An infant with thyrotoxicosis whose mother had Graves disease was treated with sodium iopanoate. Euthyroid status was achieved rapidly and maintained with minimal effort in comparison with the conventional multidrug regimen. There were no toxic effects, and hypothyroidism did not occur.

Graves Disease↗
PubMed1992

Factors controlling spontaneous human chorionic gonadotrophin in superfused first trimester placental explants.

We have recently reported that secretion of human chorionic gonadotrophin (HCG) by placental explants in superfusion is pulsatile. In this study, the factors involved in regulation of spontaneous pulsatility were examined. In superfusion, observed secretion of HCG by isolated cells was continuous, without spontaneous episodic hormonal secretion. However, this was not due to diminished viability of the cells since these cells continued to secrete sex steroids. In addition, the stimulatory response of HCG to a highly effective dose of 10(-9) M gonadotrophin releasing hormone (GnRH) analogue was also maintained. Preincubation of explants with low concentrations of cycloheximide (10(-6)M) markedly reduced baseline HCG levels as well as pulse amplitude, suggesting that episodic hormone secretion is in part dependent on protein synthesis. Moreover, preincubation of explants with labelled leucine has shown that the secretion of placental proteins is also episodic in superfusion. The pattern was similar but not identical to that of HCG. Addition of 1 min pulses of CaCl2 caused a significant release of HCG by superfused explants, suggesting that HCG secretion occurs through the release of storage granules. It was concluded that for the expression of spontaneous pulsatile secretion of HCG cell to cell contact/communication is necessary. HCG secretion is likely to reflect exocytosis of storage granules. HCG pulsatility is partly dependent on protein synthesis and this intermittent type of secretion can be documented by overall protein secretion by the superfused explant.

Cell Communication↗
PubMed1992

Effect of ryanodine on mitochondrial respiration.

Ryanodine is a pharmacological agent that stimulates calcium leakage into the cytoplasm resulting in an increase in tension. In skeletal muscle, ryanodine acts primarily on the sarcoplasmic reticulum whereas in smooth muscle, the sites of action are less clear. Visually, the increase in tension is slow and the time course can be mimicked by mitochondrial poisoning and the resultant leak of mitochondrial calcium into the cytoplasm. Although it has been reported that ryanodine has no effect on calcium flow into or from mitochondria, the effect of ryanodine on mitochondrial oxidative function was not studied. In the current investigation direct measurements of the effect of ryanodine on mitochondrial oxygen utilization were made. The results demonstrate that ryanodine, even at high concentrations, has no effect (stimulatory or inhibitory) on mitochondrial oxidation.

Animals↗
PubMed1992

Visual perceptual dysfunction in patients with schizophrenic and affective disorders versus control subjects.

Visual perception was evaluated with standard tests for 26 hospitalized patients with schizophrenia, 23 hospitalized patients with affective disorders, and 60 control subjects. Both patient groups differed significantly from the control group on low amplitude of accommodation, esophoria or exophoria, vergence duction suppression, and convergence and divergence recovery ductions. Only the affective group showed significantly reduced fusion at near distance, and only the schizophrenic group differed significantly from control subjects on disorganized left apex formation. These findings appear to confirm the presence of visual perceptual disorders that can cause disability in psychiatric patients, with important research and rehabilitation implications.

Adolescent↗
PubMed1992

M4 and M9 antibodies in the overlap syndrome of primary biliary cirrhosis and chronic active hepatitis: epitopes or epiphenomena?

Before the identification of the major mitochondrial antigens of primary biliary cirrhosis as components of the 2-oxo-acid dehydrogenase enzyme family, mitochondrial autoantigens were believed to be extremely heterogeneous and were divided into nine subtypes termed M1 to M9. This classification was based on the data derived from the relatively nonspecific biochemical and immunological techniques that were available. After the cloning and definition of the major autoantigens, more than 95% of the sera of patients with primary biliary cirrhosis were found to react with components of the 2-oxo-dehydrogenase enzymes; these enzymes correspond to the old M2 classification. Two other "M" species, dubbed M4 and M9, have attracted significant attention because they have been postulated to be prognostic indicators and more recently have been tentatively identified respectively as sulfite oxidase (EC 1.8.3.1) and glycogen phosphorylase (EC 2.4.1.1). Indeed, patients with the "overlap syndrome" are reported to have antibodies to M4 and a poor prognosis, whereas patients with antibodies to M9 have a favorable prognosis. To address the significance and definition of M4 and M9, we performed in-depth studies of sera from 11 patients with the overlap syndrome, 75 patients with primary biliary cirrhosis, 19 chronic active hepatitis patients, 13 patients with primary sclerosing cholangitis, 10 patients with cholangiocarcinoma, 20 patients with systemic lupus erythematosus, 20 patients with alcoholic cirrhosis, 17 patients with scleroderma and 30 normal individuals, using techniques of ELISA, complement fixation, immunoblotting and enzyme inhibition. We report herein that we were unable to show any disease-specific reactivity toward the proposed M4 and M9 antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Bile Duct↗
PubMed1992

Neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase deficiency in Sephardic-Jewish neonates: incidence, severity, and the effect of phototherapy.

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is frequently associated with neonatal hyperbilirubinemia, and sometimes kernicterus, often in the absence of any identifiable trigger or hematological evidence of hemolysis. The aim of this study was to compare the incidence and severity of, and the effect of phototherapy on, jaundice in G 6-PD-deficient vs G-6-PD-normal neonates in the Sephardic-Jewish community. Healthy term newborns, born to mothers of families stemming from geographic areas known to be "at risk" for G-6-PD deficiency, were screened for the condition and surveyed for hyperbilirubinemia. Seventy-five G-6-PD-deficient neonates formed the study group, while 266 neonates with normal levels of the enzyme formed the control group. Neonates with any other identifiable cause for jaundice were excluded. Phototherapy was commenced when the serum bilirubin levels reached 16 mg/dL (274 mumol/L) or more, and it was discontinued at 12 mg/dL (205 mumol/L) or less. Hyperbilirubinemia developed in 27 (36%) of the deficient neonates (serum total bilirubin greater than 13.9 mg/dL [238 mumol/L]), compared with 50 (18.8%) of control neonates (P = .002), while 20 (26.7%) of the study group required phototherapy, compared with 31 (11.7%) of control neonates (P = .002). Two neonates in the study group required exchange transfusion (serum bilirubin greater than 20 mg/dL [342 mumol/L]), vs 0 in the control group (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Asia↗
PubMed1991

Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease that includes the presence of lymphoid infiltrates in portal tracts, high titer autoantibodies against pyruvate dehydrogenase-E2 (PDH-E2) and branched chain ketoacid dehydrogenase-E2 (BCKD-E2), and biliary tract destruction. The mechanism by which the autoimmune response is induced, the specificity of damage to the biliary epithelium, and the role of T cells in PBC are still unknown. To address these issues, we have taken advantage of a mouse mAb, coined C355.1, and studied its reactivity against a panel of liver tissue from normal subjects as well as a panel of liver specimens from patients with PBC, progressive sclerosing cholangitis, and chronic active hepatitis (CAH). C355.1, much like human autoantibodies to PDH-E2, reacts exclusively by immunoblotting with PDH-E2, binds to the inner lipoyl domain of the protein, and inhibits PDH-E2 activity in vitro. In addition, we have also attempted to develop cloned T cell lines that react with PDH-E2 and/or BCKD-E2 using liver biopsies from patients with PBC, compared with CAH. Although monoclonal C355.1 produced typical mitochondrial fluorescence on sections of normal liver, pancreas, lung, heart, thyroid, and kidney, it produced a distinct and intense reactivity when used to stain the bile ducts of patients with PBC. Nine of 13 PBC liver biopsies studied herein contained bile ducts on light microscopy, all of which reacted intensely at a 1:100 culture supernatant dilution of monoclonal C355.1. In contrast, although bile ducts of liver specimens from normals, CAH, and progressive sclerosing cholangitis also reacted with C355.1, such reactivity was exclusively mitochondrial and readily detectable only at a dilution of 1:2. More importantly, we generated CD4+, CD8-, alpha beta TCR+ cloned T cell lines from patients with PBC, but not from CAH, that produced IL-2 specifically in response to PDH-E2 or BCKD-E2.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1991

Anti-pyruvate dehydrogenase autoantibodies in primary biliary cirrhosis.

Antimitochondrial antibodies (AMA) may be detected in 95% of patients with primary biliary cirrhosis (PBC). The target autoantigens for the AMA were recently identified as four closely related metabolic enzymes located in the mitochondria. We have purified the pyruvate dehydrogenase (PDH) enzyme from bovine heart, showing that all PBC sera reacted with a 74-kd band. PDH was utilized to establish an ELISA assay for detecting the relevant antibodies. One hundred twelve of 120 sera from patients with PBC (95%) reacted with the PDH but none of the 201 control sera, including normal subjects and a panel of sera from other patients with liver diseases, showed similar reactivity. In 77% of the PBC sera the anti-PDH antibody isotype was identified as a combination of IgG and IgM, while in 18% only IgM was detected. In 5% of the sera the isotype was confined to IgG. PBC sera specifically inhibited the PDH enzyme activity. The enzyme inhibition correlated with the anti-PDH antibody titers. Thus, PDH seems to be one of the major target epitopes for AMA observed in sera of patients with PBC.

Animals↗