The relevance of eicosanoids including PAF for the biochemical regulation of cardiac rhythm.
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Biomedical subjects
Publications and source records attributed to E Meyer.
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The structure of native porcine pancreatic elastase in 70% methanol has been refined using film data to 1.65 A resolution, R = 0.169. A total of 134 molecules of water (but no methanol) has been refined. This structure, because of its native state and modestly high resolution, serves as the basis for comparison with other elastase structures complexed with natural or synthetic ligands. Internal structured water occupies distinct regions. Two regions (IW1 and IW7) suggest a mechanism for equalizing 'hydrostatic pressure' related to ligand binding and release. A third region (IW4) forms part of a hydrogen-bonding network linking the catalytic Ser 195 O gamma with a remote (13.4 A) surface of the enzyme. A comparison with the structures of all known serine proteases reveals that a linkage of Ser O gamma to remote surface is conserved in all cases, suggesting that the accepted catalytic mechanism of serine proteases needs to be re-evaluated. One possible mechanism for base catalysis of Ser O gamma H proton extraction is presented.
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Acute or persistent elevations in serum C-reactive protein (CRP) concentration have been shown to be of value in diagnosing acute rejection episodes in azathioprine (AZA)-treated renal transplant recipients. To assess whether changes in serum CRP level might assist in differentiating nephrotoxicity from acute rejection in cyclosporine (CsA)-treated renal transplant recipients, we measured changes occurring in serum CRP concentrations in 74 CsA patients in response to transplant operation, acute rejection, cyclosporine nephrotoxicity, and serious infection, and compared these values with changes in AZA patients. Serum CRP concentration rose in response to operation in virtually all patients, regardless of immunosuppressive regimen, from mean baselines of 5.9 +/- 2.7 mcg/ml (AZA) and 6.8 +/- 6.5 mcg/ml (CsA) to mean peak levels of 43.8 +/- 33.4 mcg/ml and 65.1 +/- 39.5 mcg/ml, respectively. CRP rose during 76% of acute rejection episodes in AZA patients by a mean of 29.7 +/- 37.4 mcg/ml. In contrast, in 80% of acute rejection episodes of CsA patients, CRP remained undetectable or failed to rise above a stable, minimally elevated baseline. Similarly, there was no elevation in CRP in 9 of 10 episodes of nephrotoxicity. In 14 CSA patients with serious infections (8 pulmonary, 3 intraabdominal, 3 genitourinary), CRP rose by a mean of 67.7 +/- 50.7 mcg/ml. Thus, although CRP rises significantly with operation or serious infection in CsA patients, CRP fails to rise with nephrotoxicity or acute rejection.
An example of an unusual cold autoagglutinin is reported. The antibody was monoclonal IgMKappa able to fix complement, and, in the presence of albumin, had both a high titer (greater than 4,096 at 4 degrees C) and a wide thermal range (4-37 degrees C). The patient was closely followed over a 3-year period with no evidence of hemolysis ever documented, despite a persistently positive direct antiglobulin test and the presence of the cold autoagglutinin. In contrast to previous reports regarding cold-agglutinin disease, this case demonstrates that in vivo hemolysis is not always associated with cold autoagglutinins that in vitro show a high thermal range in the presence of albumin.
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The human blanching assay was used to assess the potency of two new proprietary corticosteroid creams. The blanching abilities of 0.1% desonide cream and 0.05% halometasone cream were evaluated relative to the blanching elicited by 0.05% clobetasol 17-propionate cream, 0.1% betamethasone 17-valerate cream and 0.05% clobetasone 17-butyrate cream. The results of the trial indicated that the 0.1% desonide cream falls into the potent group of topical corticosteroid preparations and the 0.05% halometasone cream falls into the moderately potent group.
Platelet-activating factor (PAF) induced arrhythmogenic effects in ouabain-induced arrhythmias and in untreated guinea pigs. The ischemic induced arrhythmias are aggravated by PAF in open-chest dogs. TX receptor antagonizing substances such as BM 13177 and specific PAF antagonists for example BN 52021 and WEB 2086, completely inhibited the PAF induced cardiac arrhythmias. An inhibitor of lipoxygenase such as esculetin inhibited the PAF effect to a small extent, too. Non-specific PAF antagonists such as diltiazem, diazepam, buphenin and trapidil have no or only a slight influence on PAF induced arrhythmias, although the antiarrhythmic effect of diltiazem and trapidil was shown on ouabain induced arrhythmias without PAF. The present study supports the hypothesis that PAF aggravates cardiac arrhythmias under pathophysiological conditions in which PAF is involved. Specific PAF antagonists and TX receptor antagonists induce antiarrhythmic effects under these conditions.
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26 homosexual men with antibodies to HIV and generalized lymphadenopathy were examined between 1982 and 1984. Lymphadenopathy was accompanied by clinical symptoms such as fever, diarrhoea and weight loss (50%), moderate leukopenia (15%), lymphocytosis (50%), hypoergy to intraepidermal skin test with recall-antigens (12%), elevated serum levels of IgG (62%), IgA (23%), IgM (19%), beta-2-microglobulin (76%) and neopterin (69%), diminished absolute numbers of CD4-helper cells in the peripheral blood (24%) and an inversion of the ratio CD4-helper cells/CD8-suppressor cells both in blood (64%) and in lymph nodes (36%). Mitogen induced lymphocyte proliferation was significantly lower and the serum levels of gamma-interferon were significantly higher than in healthy controls. Lymph node biopsy revealed only nonspecific reactive hyperplasia with follicular hyperplasia in 54%, a mixed pattern of both follicular hyperplasia and follicular involution with paracortical expansion in 25% and follicular involution with paracortical expansion in 21%. 22 patients were followed longitudinally for a median time of 37 months (33-51 months). 10 patients (46%) developed full-blown AIDS within a median period of 35 months (24-46 months) after first examination and 43 months (36-77 months) after the anamnestic onset of the lymphadenopathy syndrome. The parameters distinguishing these patients from those without progression of disease were higher serum levels of gamma-interferon, higher relative and absolute numbers of CD8-suppressor cells in the peripheral blood, a reduced number of CD4-helper cells in the lymph nodes, and a lower CD4/CD8 ratio as well in the peripheral blood as in the lymph nodes.(ABSTRACT TRUNCATED AT 250 WORDS)
In 50 patients with acute infarction who were admitted within 6 hours after the beginning of the complaints randomizedly an intravenous streptokinase short-term lysis or a conventional heparin phenprocoumon treatment was performed and 4 weeks later the results were objectified by coronarography and ventriculography. The patients were subdivided into 3 groups: 1. control group (without fibrinolysis), 2. early lysis (within 4 hours) and 3. late lysis (4-6 hours). Four weeks after the infarction the proportions of the open infarction vessels are approximately of the same size in all three groups, the functional results are best (end-diastolic pressure and kinetics of the cardiac wall) in the group of patients who underwent an early lysis. Successfully lysed patients with remaining residual stenosis must be regarded as particularly threatened by infarction and remain under special control (residual angina, ergometrically objectified exercise tolerance, perhaps coronarography) in the phase of rehabilitation.
Twelve patients were studied within 48 hours of stroke using positron emission tomography to determine cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction, cerebral blood volume, cerebral pH (CpH), and cerebral metabolic rate for glucose (CMRGlc), the last calculated using published normal rate constants (CMRGlc[N]) and those for severe ischemia. In these studies, a cortical region of severe ischemia (I) was outlined, its metabolic and perfusion properties evaluated, and its length measured. The contralateral uninvolved cortical rim (C) in these patients and the cortical rim in 5 older normal patients were used for comparison. The length of region I correlated with the neurological deficit measured independently by a clinical scoring method. The 12 patients fell into two groups: Group I (8 patients), whose CBF in I was 9.3 +/- 2.5 ml/100 gm/min (mean +/- SEM) and was in every patient lower than that in C (33.1 +/- 2.2), and Group 2 (4 patients), whose CBF in I was 42.1 +/- 8.5 ml/100 gm/min and was in every case higher than that in C (28.2 +/- 1.5). In Group I, region I showed a CMRGlc(N)/CMRO2 ratio of 0.22 +/- 0.06 and a CpH of 6.83 +/- 0.06. In Group 2, the same ratio in the region I was 0.58 +/- 0.09 and the CpH was 7.12 +/- 0.05. The CMRGlc (N)/CMRO2 ratio for the contralateral hemisphere was comparable in the two groups. Our data suggest that, within 48 hours of the clinical onset of stroke, the ischemic cortex is already reperfused in one third of patients. Those ischemic regions with persistent hypoperfusion appear acidotic, whereas in the reperfused regions, despite evidence of an increased CMRGlc/CMRO2 ratio, acidosis is not evident. The implications of these findings for therapies proposed in acute human cerebral ischemia are discussed.
Positron emission tomography was used to study the cerebral metabolic rate for glucose (CMRGlc) in 7 adult patients with generalized spike-and-wave activity in the electroencephalogram. No consistent changes were seen in the CMRGlc. There was a slight trend toward an increased CMRGlc in 2 patients with primary generalized epilepsy, while in the 5 other patients with minor deviations from this condition or with secondary generalized epilepsy, the CMRGlc was unaffected by spike-and-wave activity or was below the normal range. Neither the amount of spike-and-wave activity in the EEG nor the presence of clinically evident absence seizures appeared to influence the CMRGlc. Therefore, we conclude that neuronal activity underlying spike-and-wave discharge does not seem to require increased glucose utilization.
The operational equation for the double-label deoxyglucose method described in the following paper requires the knowledge of the rate constants for transfer of fluorodeoxyglucose across the blood-brain barrier (K1* and K2*), and those for phosphorylation of fluorodeoxyglucose (K3*) and dephosphorylation of fluorodeoxyglucose-6-phosphate (k4*). These rate constants were determined in anesthetized rats by external coincidence counting. Radioactivity in parietal brain was measured for a 110 min experimental period after a bolus injection of 18F-labeled fluorodeoxyglucose. Apparent rate constants were obtained by fitting the resulting tissue radioactivity curves to the tissue radioactivity function of the deoxyglucose model modified to take into account the dephosphorylation of fluorodeoxyglucose-6-phosphate. The apparent fluorodeoxyglucose rate constants in rat brain are K1* = 0.195 ml g-1 min-1, k2* = 0.379 min-1, k3* = 0.088 min-1, and k4* = 0.009 min-1.