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Biomedical subjects

M Kaplan

Publications and source records attributed to M Kaplan.

At least 199 records · Page 11Linked to original sources
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↗
PubMed1991

AIDS knowledge and beliefs, and sexual behavior of sexually delinquent and non-delinquent (runaway) adolescents.

This study assessed general knowledge of AIDS, beliefs about preventing AIDS, and sexual behavior among two groups of male adolescents at high risk of HIV/AIDS: 60 sexually delinquent males and 57 non-delinquent runaway males. Significantly fewer sexually delinquent than non-delinquent (runaway) males had experienced sexual intercourse with a consenting female partner (45 vs. 89 per cent). Sexually delinquent youths scored significantly lower than non-delinquent youths in general knowledge of AIDS (65 vs. 73 per cent) and were not able to discriminate safer behaviors from those which were less safe (42 vs. 71 per cent). Both groups reported moderate support for beliefs about preventing AIDS. These results suggest HIV/AIDS prevention programs that attempt to increase knowledge are needed by these youths, particularly for sexually delinquent youths.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Stress-related hormones affect human chorionic gonadotrophin secretion from the early human placenta in vitro.

The effect of a physiological range of concentrations of three stress-related hormones, oxytocin (OT), arginine-vasopressin (AVP) and prolactin (PRL) was tested upon human chorionic gonadotrophin (HCG) secretion by placental explants from early pregnancy in static and superfusion cultures. In static cultures, OT and AVP significantly increased HCG secretion, whereas PRL had no effect. In superfusion, 1-min pulses of OT induced a significant (two- to 10-fold) rise in HCG pulse amplitude compared to the control. This effect of this neuropeptide was blocked by coadministration of a specific receptor antagonist. AVP also increased the glycoprotein pulse amplitude by two- to five-fold, but only with every second pulse administered. PRL pulses caused a progressive inhibition of spontaneous HCG pulsatility. In conclusion, stress-related hormones affect placental HCG secretion in vitro. The involvement of these factors in impairing early pregnancy development is suggested.

Arginine Vasopressin↗
PubMed1991

The effect of progesterone upon first trimester trophoblastic cell differentiation and human chorionic gonadotrophin secretion.

The effect of progesterone (P) upon first trimester placental secretion of human chorionic gonadotrophin (HCG) and cellular differentiation was studied using both static and kinetic methods. At 1 microM, P inhibited spontaneous episodic secretion of HCG when given in short pulses (1-4 min) to placental explants in superfusion. Both HCG pulse frequency and amplitude were reduced. At 0.1-0.01 microM P concentrations, the effect of HCG secretion was milder. P also blocked the maximally effective concentration 100 pM of gonadotrophin releasing hormone (GnRH) analogue, a known HCG stimulant, when given together with it for 1 min. This inhibitory effect lasted for 1 h after P administration. Progesterone at 1 microM, added daily for 1 week blocked HCG secretion by isolated trophoblastic cells in static culture. This inhibitory effect lasted until the fifth day. No effect on differentiation and long-term viability was noticed in P-treated cells. Incubation with 0.1-1.0 microM P did not affect HCG secretion by explants after 24 h. In contrast, the effect of 1 microM cortisol or 1 nM oestradiol was stimulatory. In conclusion, P exerts both a rapid and delayed inhibitory effect upon HCG secretion and production. It may do so by counteracting the stimulatory effect of endogenous GnRH on gonadotrophin secretion by the placenta.

Cell Differentiation↗
PubMed1991

Comparative stimulatory effect of gonadotrophin releasing hormone (GnRH) and GnRH agonist upon pulsatile human chorionic gonadotrophin secretion in superfused placental explants: reversible inhibition by a GnRH antagonist.

The roles of gonadotrophin releasing hormone (GnRH) and a GnRH agonist (GnRHa) (D-Ala6-Met-Leu7-Pro-N-ethyl-amide) in controlling pulsatile human chorionic gonadotrophin (HCG) secretion by superfused placental explants in the first trimester were examined. One minute pulses of both GnRH and GnRHa had a biphasic effect upon pulsatile HCG secretion. GnRHa was maximally effective at 10(-10) M concentration, at 10(-11) M the effect was mild while at 10(-8) M, no effect was noted. GnRH exerted a maximal stimulatory effect at 10(-8) M; at 10(-10) M no effect was seen, while at 10(-7) M the effect was mildly stimulatory. This was evaluated by carrying out both a between and within channel type of analysis. The effect of a GnRH antagonist GnRH(ant) upon GnRH and GnRHa-induced HCG secretion was examined. Explants were incubated overnight with 10(-8) M GnRH(ant), which was also continuously administered during superfusion. The addition of 1-min pulses of GnRH and GnRHa during the exposure to GnRH(ant) failed to stimulate pulsatile HCG secretion. This effect was reversible since the response to GnRH was restored within 10 min after stopping GnRH(ant) administration. In addition, by the third cycle, co-administration of GnRH(ant) for 2 min together with 10(-10) M GnRHa for 1 min completely blocked the GnRHa-induced effect. Continuous administration of 10(-8) M GnRH(ant) decreased spontaneous HCG pulse amplitude and the area under the curve but failed to modify pulse frequency. In conclusion, GnRH appears to exert a receptor-dependent stimulatory effect upon pulsatile HCG secretion in superfusion in the first trimester placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

The effect of ice on intra-articular temperature in the knee of the dog.

The effect of surface cooling on intra-articular temperature was examined in dogs' knees. Four treatment protocols were examined: local ice compress application for 5, 15 and 30 min and local ice bath immersion for 15 min. Intra-articular temperatures were recorded using a needle microprobe inserted into the knee and continuous temperature recordings were made before, during and after the treatment. Rectal temperatures were also simultaneously recorded. Intra-articular temperatures rapidly dropped during icing. Five minutes of ice compress application resulted in a 2.2 +/- 1.2 degrees C intra-articular temperature drop with no change in rectal temperature. After 15 min of ice compress application, the joint temperature fell 4.1 +/- 1.3 degrees C with no change in rectal temperature. Thirty minutes of local ice compress application dropped the knee temperature 6.5 +/- 4.0 degrees C with a slight 0.5 +/- 0.3 degrees C drop in rectal temperature. Fifteen minutes of ice water immersion caused a much greater drop in intra-articular temperatures (20.2 +/- 8.4 degrees C) than could be achieved with ice compress. Rectal temperatures fell slightly during immersion (1.6 +/- 0.3 degrees C). After the removal of any type of cryotherapy, intra-articular temperatures continued to drop for several minutes and then a prolonged rewarming period commenced. The mean time required to return to baseline intra-articular temperature varied from 22-60 min, depending on the type and duration of cryotherapy. We conclude that brief periods of topical cold application to a dog's knee can induce significant and long lasting depression of intra-articular temperatures and that this is a local effect not dependent on core temperature cooling.

Animals↗
PubMed1991

Patterns of spontaneous pulsatile secretion of human chorionic gonadotropin and pregnancy specific beta 1 glycoprotein by superfused placental explants in first and last trimester. Lack of episodic human placental lactogen secretion.

We have recently reported that during superfusion of placental explants, human chorionic gonadotropin secretion is episodic. In the present work we have examined, using the superfusion model, the pattern of secretion of other glycoprotein hormones, pregnancy specific beta 1 glycoprotein and human placental lactogen, in the first trimester and term placenta. This was done by evaluating the pulsatile pattern by two different computerized programmes. By using different sampling intervals (6-0.5 min) of the effluent, two distinct patterns of hCG secretion were detected in the first trimester: a short one, occurring every 8-9 min and the other every 18-25 min. In contrast, at term the only episodic pattern detected was every 40-50 min, with a low amplitude, 20-30% above baseline, and a declining baseline. In two out of seven placentas, no pulsatility was detected. The secretion of pregnancy specific beta 1 glycoprotein was pulsatile, occurring every 14-15 min in the first trimester and every 6-7 min at term. Finally, the secretion of human placental lactogen at term was not pulsatile. The levels of this glycoprotein in the first trimester placenta were below detection limits. In conclusion, the patterns of the three glycoproteins during superfusion are different, suggesting different paracrine/autocrine control mechanisms. The dynamic superfusion model also enables identification of thus far not reported gestational age-dependent differences in the secretion pattern of hCG and pregnancy specific beta 1 glycoprotein.

Chorionic Gonadotropin↗
PubMed1991

Angle-specific torques of thigh muscles: variability analysis in 200 healthy adults.

This study evaluated the variability of the isokinetic angle-specific torques (ASTs) at 15 and 75 degrees of knee flexion and assessed the relationship between them and the isokinetic peak torque (PT) in 200 healthy adults. The results showed that the value of these AST measurements was lower than of the PT measurements. This was due to larger variability of the AST (male and female coefficient of variation [cv] 34 and 43% in the ASTs vs. 19 and 31% in the PTs); unequal variation in the results between men and women (mean cv 27% in men vs. 34% in women); and fairly poor prediction of the ASTs from the PT (PT accounted for only 39 and 62% for the variation seen in the men's and women's AST results). Furthermore, in regression analysis the standard errors of the estimates were unacceptably high, averaging 26%. AST measurements should not be used routinely.

Adolescent↗
PubMed1990

Reduction of myocardial ischemia during percutaneous transluminal coronary angioplasty with oxygenated Fluosol.

The effects of perfusion of an oxygen-carrying perfluorochemical emulsion (Fluosol) in alleviating symptoms of myocardial ischemia during balloon occlusion were examined in a multicenter trial of 245 patients. Severe anginal pain occurred less frequently in patients receiving Fluosol perfusion (21%) than in those receiving routine angioplasty (34%) (p less than 0.05). ST-segment changes at balloon deflation in routine angioplasty patients were significantly greater than in patients who received oxygenated Fluosol perfusion (2.2 +/- 1.2 vs 1.7 +/- 0.9 mm; p less than 0.03). Profound regional wall dysfunction (-561 +/- 224 U) was observed in routine angioplasty patients by 2-dimensional echocardiography. Patients receiving oxygenated Fluosol perfusion, however, maintained near baseline levels of ventricular function (-61 +/- 335 U) during occlusion (p less than 0.0001). Mean global left ventricular ejection fraction was preserved at baseline levels during balloon inflation in patients perfused with oxygenated Fluosol but decreased significantly (p less than 0.001) during occlusion in routine angioplasty patients. A total of 26 complications (19 routine group; 7 perfusion group) was reported. Adverse responses to the perfusate were infrequent, occurring in 1.6 and 2.0% of patients after the test dose and during perfusion, respectively. Thus, transcatheter perfusion with an oxygen-carrying perfluorochemical emulsion is effective in alleviating myocardial ischemia during angioplasty and can be safely administered in this patient population.

Aged↗
PubMed1990

The relative affinity of recombinant dihydrolipoamide transacetylase for autoantibodies in primary biliary cirrhosis.

In normal individuals there is an adaptive immune response to a foreign antigen in which antibodies of increasing affinity are produced with time. This is not always true of an autoimmune response. However, because only a limited number of autoantigens have been cloned or purified, this issue has not been studied well. In primary biliary cirrhosis the predominant manifestation of autoimmunity is antimitochondrial antibodies that react with dihydrolipoamide transacetylase. The availability of recombinant dihydrolipoamide transacetylase and the development of a rapid and reproducible enzyme-linked immunosorbent assay for autoantibodies has allowed us to address the affinity of autoantibodies using thiocyanate inhibition. Thiocyanate is a chaotropic compound known to inhibit antigen-antibody binding in a concentration-dependent manner. We used this property to inhibit the binding by enzyme-linked immunosorbent assay of human recombinant dihydrolipoamide transacetylase with serum autoantibodies from 55 patients with primary biliary cirrhosis. The relative affinity and serum autoantibody titers were then compared with the histological stage of the liver biopsy sample. Interestingly, we found a considerable heterogeneity of relative affinities. These relative affinities did not correlate with the histological stage or the serum titer of antimitochondrial antibodies. However, the ability of serum autoantibodies to inhibit intact primary biliary cirrhosis enzyme activity was found to correlate highly (R2 = 0.751) with the relative affinity. Thus there are profound differences between patients with respect to qualitative expression of autoantibodies. The significance of this data will be unclear until more is determined regarding the nature of the epitope that drives T cells and leads to B-cell responses.

Acetyltransferases↗
PubMed1990

Inhibition of alpha-ketoglutarate dehydrogenase activity by a distinct population of autoantibodies recognizing dihydrolipoamide succinyltransferase in primary biliary cirrhosis.

Sera from patients with primary biliary cirrhosis contain autoantibodies that recognize mitochondrial proteins. Five of the target autoantigens have now been identified as enzymes of three related multienzyme complexes: the pyruvate dehydrogenase complex, the branched chain alpha-ketoacid dehydrogenase complex and the alpha-ketoglutarate dehydrogenase complex. Each complex consists of component enzymes designated E1, E2 and E3. In this report, we confirm that primary biliary cirrhosis sera react with dihydrolipoamide succinyltransferase, the E2 component of alpha-ketoglutarate dehydrogenase complex. Seventy-three of 188 (39%) primary biliary cirrhosis sera reacted with alpha-ketoglutarate dehydrogenase complex-E2 when immunoblotted against purified alpha-ketoglutarate dehydrogenase complex; one of these sera also reacted with the E1 component. In addition, primary biliary cirrhosis sera possessing alpha-ketoglutarate dehydrogenase complex-E2 reactivity specifically inhibited enzyme function of alpha-ketoglutarate dehydrogenase complex. Enzyme activity was not affected by primary biliary cirrhosis sera that contained autoantibodies to pyruvate dehydrogenase complex-E2 and/or branched chain alpha-ketoacid dehydrogenase complex-E2, which lacked alpha-ketoglutarate dehydrogenase complex-E2 reactivity. Furthermore, affinity-purified primary biliary cirrhosis sera against alpha-ketoglutarate dehydrogenase complex-E2 inhibited only alpha-ketoglutarate dehydrogenase complex activity but did not alter enzyme activity of either pyruvate dehydrogenase complex or branched chain alpha-ketoacid dehydrogenase complex. Finally, alpha-ketoglutarate dehydrogenase complex-E2 specific affinity-purified antisera did not react on immunoblot with any component enzymes of pyruvate dehydrogenase complex or branched chain alpha-ketoacid dehydrogenase complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1990

Gender differences in tobacco use in Kenya.

This study has assessed gender differences in smoking and the use of smokeless tobacco for younger adults and their parents in samples from five ethnic groups in Kenya. These samples were from two groups of pastoralists (the Maasai and the Samburu), a group engaged in fishing and farming (the Luo), and two groups of relatively Westernized Kenyans primarily involved in commercial occupations (from the Kisii and the Gikuyu ethnic groups). In four of the five study groups, there was little or no difference in the prevalence of smokeless tobacco use in either the younger or older generation. Similarly, in four of the study groups there was little or no gender difference in the prevalence of smoking for the older generation. In contrast, for the younger generation in every study group except the Luo, men were much more likely than women to smoke cigarettes. The attitudes toward tobacco use reported by the younger generation showed similar patterns. In every study group except the Luo, the younger adults reported that smokeless tobacco use was socially acceptable for both men and women, but smoking was acceptable only for men. Many of the younger women reported that they did not smoke because it would not be socially acceptable. The interview data suggest that the social prohibition against women's smoking was one component of more general restrictions on women's behavior, and the absence of restrictions on men's smoking was related to men's greater social power. The Luo were the only study group in which respondents reported that women should have as much influence as men in decision making. Correspondingly, the Luo were the only study group in which most respondents considered it acceptable for women to smoke and women were as likely as men to smoke cigarettes.

Age Factors↗
PubMed1990

Radioiodinated ligands for the estrogen receptor: tissue distribution of 17 alpha-[125I]iodovinylestradiol derivatives in normal and tumor-bearing adult female rats.

A series of three 125I-labeled 17 alpha-iodovinylestradiol derivatives previously demonstrated to have a selectivity for estrogen receptor tissues in immature female rats were selected for further evaluation in adult female rats. In normal adult female rats, the iodovinyl analogs of moxestrol (IV beta ME2), and moxestrol-3-O methyl ether (IV beta ME2-3-OMe) demonstrated high uterine uptake (0.296-0.437 and 0.135-0.199%ID-kg/g) and selectivity (10-18:1) over the 6 h time period. Subsequent evaluation in two tumor models indicated that [125I]V beta ME2 also possessed the highest tumor uptake and selectivity in the adult female rats bearing the estrogen responsive 9,10-dimethyl-1,2-benzanthracene(DMBA)-induced mammary tumors and that this was receptor mediated. An estrogen independent tumor, the transplanted Walker 256 mammary adenocarcinoma, showed no selectivity of radioligand uptake compared with nontarget tissues. The results suggest the applicability of this agent to the in vivo detection and characterization of estrogen responsive tumors in man.

9,10-Dimethyl-1,2-benzanthracene↗