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Biomedical subjects

W Schulte

Publications and source records attributed to W Schulte.

At least 55 records · Page 3Linked to original sources

Purification and partial characterization of the major cysteine protease from Entamoeba invadens.

The purification and partial characterization of a major protease from the parasitic protozoon of reptiles, Entamoeba invadens, is described. The enzyme has a molecular mass of 28 kDa, and three distinct isoelectric points at pH 4.7, 5.7 and 6.3, respectively. As an endopeptidase the enzyme digests denatured protein substrates, such as azocasein with an optimal turnover rate at pH 4.8 with a temperature optimum of 48 degrees C. The protease exhibits exopeptidase activity towards arginine containing dipeptide derivatives. Thus, it splits the chromogenic substrates N-benzyloxycarbonyl-arginine-arginine-4-methoxy-beta-naphthylamide and arginine-arginine-4-methoxy-beta-naphthylamide in the ratio of velocities of 3:1. The kinetic constants for the hydrolysis of N-benzyloxycarbonyl-arginine-arginine-4-methoxy-beta-naphthylamide are: Km 22 microM and kcat 172 s-1. The enzyme is activated by the thiol reagents cysteine and dithiothreitol and is inhibited by typical cysteine protease inhibitors, such as cystatin, E-64, iodoacetamide and p-chloromercuribenzoate. Although in many of its characteristics it resembles the cathepsin B-like cysteine protease from Entamoeba histolytica, the two enzymes were found to be immunologically different.

Animals↗

Efficacy of four antihypertensive drugs (clonidine, enalapril, nitrendipine, oxprenolol) on stress blood pressure.

The impact of 4 antihypertensive drug regimens on blood pressure (BP) during everyday life stress and on BP during experimental stress in the laboratory was examined in an open clinical study. Sixty middle-aged men with mild-to-moderate essential hypertension never previously treated were treated either with low-dose clonidine (n = 10), oxprenolol (n = 20), nitrendipine (n = 20) or enalapril (n = 10). Before therapy, all 4 groups did not differ in age, weight, degree of obesity, BP at work site and casual BP measured in the outpatient clinic. After 6 months of effective therapy (casual BP within the normotensive range), casual diastolic BP was identical among the 4 groups, whereas systolic BP was lower in patients treated with clonidine or oxprenolol than in those who received enalapril. A disparate pattern of antihypertensive efficacy among the 4 groups emerged when stress BP was compared, with average ambulatory BP higher in patients receiving clonidine or enalapril than in those who had oxprenolol or nitrendipine. During ambulatory BP monitoring, patients treated with oxprenolol had the lowest level at each level of physical activity and self-reported emotional arousal. During bicycle exercise, patients receiving clonidine had the highest increase in systolic BP and those administered oxprenolol the lowest, whereas the BP response during mental stress was similar among all 4 therapeutic groups. The analysis of the hemodynamic response pattern during mental stress unmasked further disparities. Oxprenolol provoked an abnormal hemodynamic response during mental stress tests (increase in total peripheral resistance), whereas nitrendipine and enalapril preserved the physiological hemodynamic profile (decrease of total peripheral resistance).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Continuous systemic 5-fluorouracil infusion in advanced colorectal cancer: results in 91 patients.

Ninety-one patients with metastatic colorectal cancer were treated with continuous ambulatory 5-fluorouracil (5FU) infusion 250-300 mg/m2/day through a chronic indwelling central venous catheter. Twenty-six of the 91 patients (29%) had received previous bolus 5FU. Fifty-eight of the 91 patients (64%) had two or more sites of disease, and 74 of 91 patients (81%) had liver metastases. Results were complete remission in 5 of 91 (6%), partial remission in 25 of 91 (27%), stable disease in 33 of 91 (36%), and progressive disease in 28 of 91 (31%), for an overall response rate of 30 of 91 (33%); median duration of response was 7 months. Twenty-six of 65 previously untreated patients (40%) experienced objective response. Median survival from initiation of treatment for all patients was 11 months. Forty-one percent of patients experienced no significant toxicity and were able to continue therapy without treatment interruption. Toxicities necessitating treatment interruption included stomatitis in 35 patients (39%), hand-foot syndrome in 33 patients (36%), and diarrhea in 10 patients (11%). No significant myelosuppression or serious catheter-related complications were encountered. We conclude that continuous systemic venous infusion of 5FU produces a higher response rate than traditional bolus 5FU schedules, with apparent enhancement of survival and easily managed toxicity.

Adult↗

History of dementia and Parkinson's disease in 1st-degree relatives of patients with Alzheimer's disease.

We assessed the family history of dementia and Parkinson's disease in 198 Dutch patients with Alzheimer's disease diagnosed before the age of 70 years, and in 198 age- and sex-matched healthy population controls. Of the Alzheimer patients, 48% had at least 1 1st-degree relative with dementia, compared with 19% of the controls. There were 24 patients and 1 control with 2 or more 1st-degree relatives with dementia, yielding a relative risk of 40.0. More Alzheimer patients than controls had a 1st-degree relative with Parkinson's disease, with a relative risk of 2.9. This study strongly confirms earlier findings of familial aggregation of Alzheimer's disease and provides evidence for familial aggregation of Alzheimer's disease with Parkinson's disease. The latter may point at a joint etiology of these diseases.

Age Factors↗

Disparities in blood pressure control under various antihypertensive regimens.

Ambulatory blood pressure recordings and stress blood pressures during exercise were compared among hypertensive patients effectively treated with oxprenolol, nitrendipine, enalapril or low-dose clonidine. After 6 months of therapy, the means of blood pressure at rest and casual diastolic pressure were nearly identical among the four therapeutic groups. Although all pressures fell to within the normotensive range, casual systolic pressures were lower in patients treated with sympatholytic agents than in those taking enalapril. In contrast, average ambulatory blood pressure was less controlled in patients given clonidine or enalapril than in those given oxprenolol or nitrendipine. During physical stress patients taking clonidine showed the highest stress blood pressures and those taking oxprenolol the lowest pressures. The study demonstrated that although blood pressure was reduced to within the normotensive range in all four therapeutic groups, analysis of values of ambulatory blood pressure and stress blood pressure during physical activity showed a disparate pattern of antihypertensive efficacy.

Antihypertensive Agents↗

A comparative study of results with various endosseous implant systems.

The results of regular follow-up of various endosseous titanium implant systems are presented together with an overview of the results with Tübingen Frialit aluminum oxide ceramic implants. Using ITI implants, pathological findings for sulcus depth and peri-implant bone degradation were found significantly more frequently than with the other titanium implants. Clinical mobility was present significantly more frequently with TPS implants than with the IMZ system, whereas an increase in the depth of the peri-implant sulcus alone occurred significantly more frequently with the IMZ and ITI than with the TPS implant system. The observation period for Brånemark implants is too short to permit final evaluation. However, pathological findings have not occurred to date.

Dental Implantation, Endosseous↗

Hemodynamic response patterns to mental stress: diagnostic and therapeutic implications.

Stress has been identified as contributing to the development of cardiovascular disease. The pathophysiologic link between stress and disease still remains unclear. Because experimental stress testing in the laboratory permits the examination of the underlying mechanism for stress-induced blood pressure, analyses of cardiovascular reactivity during emotional stress could be of particular clinical importance. The analyses of pooled data during the past 6 years (n = 298, age from 20 to 60 years, normotensive subjects as well as patients with borderline and mild essential hypertension) reveal that stress-induced changes in stroke volume and especially in total peripheral resistance are crucial parameters to analyze the hemodynamic stress response. However, neither those simple nor complex response patterns such as "hot reactor" describe clinically distinct subgroups of persons. When physiologic testing was repeated in hypertensive patients after effective long-term antihypertensive therapy with clonidine, oxprenolol, nitrendipine, or enalapril, no attenuation of the stress-induced increase in blood pressure was found in any of these groups. However, heart rate reactivity and stress-induced changes in total peripheral resistance were altered significantly by oxprenolol and nitrendipine. The beta-adrenoceptor blocker decreased heart rate reactivity and increased reactivity of peripheral resistance; the calcium antagonist decreased stress-induced changes in peripheral resistance and increased the heart rate response. The centrally acting sympatholytic regimen and the angiotensin-converting enzyme inhibitor had no impact on the hemodynamic response pattern during emotional challenge.

Adult↗

Sodium intake modulates left ventricular hypertrophy in essential hypertension.

In order to assess the impact of dietary sodium intake on the degree of left ventricular hypertrophy, we determined posterior wall thickness, relative wall thickness and left ventricular mass by two-dimensionally guided M-mode echocardiography, and related these parameters to sodium excretion over 24 h. There was no restriction on sodium intake. The first cohort comprised 43 subjects (residents of New Orleans) with mild to moderate essential hypertension who had not been treated for at least 4 weeks; in this cohort sodium excretion correlated with posterior wall thickness (r = 0.64, P less than 0.001), relative wall thickness (r = 0.67, P less than 0.001) and left ventricular mass (r = 0.37, P less than 0.02). A stepwise multiple regression analysis confirmed that sodium excretion was a determinant of posterior wall thickness (P less than 0.02) and relative wall thickness (P less than 0.05) independently of age, arterial pressure and body weight. The second cohort comprised 60 white male patients (residents of Bonn) with mild essential hypertension who had never been treated in the past; in this cohort sodium excretion correlated with diastolic diameter (r = 0.36, P less than 0.001) and with left ventricular mass (r = 0.35, P less than 0.001). Sodium excretion and systolic pressure emerged as independent variables (P less than 0.02) for left ventricular mass as evaluated by multiple regression analysis. These results identify dietary sodium intake as an independent powerful determinant of left ventricular hypertrophy in two disparate patient cohorts. Thus, for a similar haemodynamic load, sodium intake might accelerate, and conversely salt restriction mitigate, cardiac structural adaptation in patients with essential hypertension.

Cardiomegaly↗

On the specificity of a cysteine proteinase from Entamoeba histolytica.

A cysteine proteinase has been isolated from the virulent strain HM1:IMSS of Entamoeba histolytica by two gel chromatography steps, ion exchange chromatography on DEAE-cellulose and affinity chromatography on organomercurial-Sepharose. The purified proteinase was homogeneous, as judged by polyacrylamide gel electrophoresis in the presence and in the absence of sodium dodecyl sulphate, and was a monomeric protein with a relative molecular mass of Mr 27000 +/- 2000 possessing an N-terminal alanine. The enzyme was inhibited by natural and synthetic inhibitors against cysteine proteinases. Split experiments employing blocked and unblocked peptide analogues with -2-naphthylamide moieties indicate that the cleavability was enhanced by the presence of basic residues, such as arginine or lysine, near the acyl end of the substrate. With unblocked tetrapeptides as substrates, exopeptidase activity of the amebic enzyme required an arginine at the P2-position, lysine could not substitute for arginine. The protease was able to digest native collagen type I, with an initial attack at the alpha 2-chain of the molecule.

Animals↗

Conservative treatment of occlusal dysfunctions.

The paper discusses 20 years of experience with a physiotherapeutic programme that can be used in the initial therapy of myoarthropathies of the temporomandibular joint of both psychosomatic and artificial occlusal origin. The principle is to re-train the masticatory musculature, which has become incoordinated as a result of occlusal parafunctions. The therapy aims to treat symptomatic problems. It can be used with a high success rate in functional disturbances of the stomatognathic system of psychosomatic, artificial occlusal and external traumatic origin.

Exercise Therapy↗

Impact of antihypertensive therapy on blood pressure reactivity during mental stress.

The effects of baseline antihypertensive drugs or sympatholytic agents on the characteristic hemodynamic response pattern (i.e. increase in blood pressure and heart rate, decrease in total peripheral resistance) during emotional stress were examined. Middle aged male caucasian patients with hitherto untreated mild essential hypertension were given nitrendipine 10-20 mg per day, oxprenolol 160 mg per day or clonidine 75-300 micrograms per day until casual blood pressure was below 140/90 mmHg for at least three months. Blood pressure, heart rate and stroke volume was assessed, at rest and during emotional stress, before and during effective antihypertensive therapy. The increase in systolic pressure during stress was not attenuated by any of the drugs. Heart rate reactivity was lowest when patients received oxprenolol, but peripheral resistance during emotional stress was significantly increased. Clonidine had no unfavorable effects on the hemodynamic pattern during emotional stress but nitrendipine decreased peripheral resistance even more than the decrease in resistance observed during stress before initiation of therapy. If one accepts that antihypertensive therapy should not alter a physiological hemodynamic pattern to an unphysiological response, psychophysiological examinations seem to be valid in selecting suitable patients for the different alternatives in antihypertensive therapy.

Adult↗

Specificity of a cysteine proteinase of Entamoeba histolytica towards the alpha 1-CB2 peptide of bovine collagen type I.

The cysteine proteinase of Entamoeba histolytica was shown to hydrolyze the cyanogen bromide peptide alpha 1-CB2 of calf skin collagen type I yielding two split products. Amino acid analyses of the formed peptides and estimation of the amino-terminal residues revealed that the alpha 1-CB2 peptide was exclusively cleaved between Gly10 and Leu11 within the sequence -Arg9-Gly10-Leu11-yielding two peptides with 7 and 29 amino acids, respectively. Under identical conditions the ratio of hydrolysis of the Gly10-Leu11 bond in the alpha 1-CB2 peptide to the Gly23-Phe24 bond within the internal sequence -Arg22-Gly23-Phe24- of bovine insulin B-chain was 100:65. The enzyme was found to split both benzyloxycarbonyl-Arg-Arg-methoxy-2-naphthylamide and benzyloxycarbonyl-Arg-Gly-2-naphthylamide. The ratio of hydrolysis of these substances was 100:11.6. Benzyloxycarbonyl-Gly-Arg-2-naphthylamide was a very poor substrate for the enzyme.

Amino Acids↗

Hemodynamic and neurohumoral effects of low-dose clonidine in mild to moderate hypertension.

To evaluate the role of the sympathetic nervous system in essential hypertension and the influence of clonidine, 28 male subjects with mild to moderate hypertension were either treated with low-dose clonidine (n = 14, mean age: 42.4 +/- 2.1 years) or were randomized to a nontreated control group (n = 14, mean age: 40.2 +/- 2.4 years). Clinical blood pressure and heart rate were assessed, and after 4 weeks of treatment plasma catecholamines and the hemodynamic response to mental arithmetic, cold stimulation, and ergometric exercise were compared between both groups. Under therapy with 0.075 mg of clonidine per day casual blood pressure dropped and diastolic BP was significantly lower than in the control group. Heart rate did not change. After 4 weeks the plasma levels of epinephrine and norepinephrine were the same in both groups. During mental arithmetic total peripheral resistance decreased in the treated group while it did not change in the control group, but both groups did not differ in their percentage changes in the hemodynamic parameters in response to the three stress tests. It has been concluded that clonidine reduces sympathoadrenergic activity, but in a low dosage this effect is obviously restricted to a reduction of arteriolar tone.

Adult↗