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Biomedical subjects

H M Müller

Publications and source records attributed to H M Müller.

At least 91 records · Page 5Linked to original sources

The T cell reactivity against the major merozoite protein of Plasmodium falciparum.

We have undertaken a systematic search for T cell epitopes within the sequence of the major merozoite surface antigen (GP190) of Plasmodium falciparum. Recombinant polypeptides expressed in E. coli were used to evaluate the reactivity of peripheral blood mononuclear cells (PBMC) from both inhabitants of a rural community of West Africa exposed to P. falciparum transmission and from German patients with diagnosis of acute malaria. Although the proliferative response of the PBMC was in most cases very low, several T cell clones could be established. Deletion analysis of each gp190-derived polypeptide allowed the identification of six different T cell epitopes. Epitopes could be mapped within the dimorphic region of gp190, which also contains the sequences most frequently recognized by sera from adult individuals living in endemic areas.

Adult↗

[Effect of temperature on the growth of Penicillium from moldy feed].

178 Penicillium strains were isolated from moulded feedstuffs (mainly corn and wheat after ambient air drying, wheat after refrigeration, corn after treatment with propionic acid), and investigated for the effect of temperature on growth rate. Temperatures between 4 and 27 degrees C were used. 159 strains proved psychrotrophic, they were able to grow at 4 degrees C on malt extract agar (MA) as well as in wheat; the growth in wheat was indicated by the production of ergosterol. On MA all psychrotrophic strains were able to grow also at 10-27 degrees C. The maximum rate of growth was reached at 10-15 degrees C, 15-20 degrees C, 20-27 degrees C, or must be assumed for temperatures greater than or equal to 27 degrees C. At 4 and 10 degrees C the mean growth rate on MA was 24 and 51%, respectively, related to the mean rate at 20 degrees C; the lower temperature limit of growth was found at - 1 degree C by graphic extrapolation. The Q10 value of growth on MA is about 2, if temperatures between 20 and 10 degrees C are compared; with decreasing temperature higher Q10 values up to 3.7 are obtained. The growth rate of a strain of Penicillium aurantiogriseum on wheat was affected by temperature nearly in the same manner as on malt extract agar. The results are discussed with respect to the risk of moulding during refrigerated storage of feedstuffs.

Animal Feed↗

[Ergosterol as a measure for fungal growth in feed. 2. Ergosterol content of mixed feed components and mixed feed].

Ergosterol was determined as a chemical indicator of fungal biomass in commodities which were used for the production of mixed feeds. It was found in all samples of each of the following components (content in mg/kg DM): Wheat (2.6 +/- 1.0), low grade wheat flour (fibre less than or equal to 3.5%) (17.3 +/- 9.1), wheat semolina bran (fibre less than or equal to 10%) (29.4 +/- 16.8), wheat bran (35.2 +/- 9.4), grain corn (1.0 +/- 0.6), corn gluten feed (7.8 +/- 3.0), corn gluten (10.3 +/- 5.0), maize germ meal (8.0 +/- 2.0), barley (3.1 +/- 1.1), malt sprouts (40.6 +/- 15.9), broad beans (0.6 +/- 0.3), peas (summer varieties, white flowering) (2.2 +/- 1.0), soya flakes (2.2 +/- 0.9), soya meal (1.1 +/- 0.7), sunflower meal (5.0 +/- 2.4), copra meal/expeller (9.1 +/- 1.6), palm kernel meal (12.6 +/- 11.0), rapeseed meal (2.6 +/- 0.8), linseed meal (3.2 +/- 1.6), manioc meal (8.3 +/- 2.7), beet pulp, dried (1.6 +/- 0.3), beet pulp with molasses (2.2 +/- 0.9), alfalfa meal (37.8 +/- 10.4), grass meal (62.4 +/- 37.0). Ergosterol was not found in molasses, citrus pulp, carcass meal, meat-and-bone-meal, skim milk powder, whey powder, fish meal (2 of 3 samples), mineral components, vitamin mixtures and other additives. Differences in ergosterol contents are discussed. With four mixed feeds it was demonstrated that the ergosterol content determined chemically in the mixture is in good accordance with the value calculated from the ergosterol content of the components and their percentage in the mixture.

Animal Feed↗

A new tool for the serodiagnosis of acute Plasmodium falciparum malaria in individuals with primary infection.

We have developed an ELISA which detects, with high specificity, antibodies against a major surface protein of P. falciparum merozoites which is a processing product of the precursor glycoprotein gp190. This assay can be used in the diagnosis of acute malaria in individuals with primary infection. Two partial sequences of gp190 were expressed in E. coli as beta-galactosidase (beta-Gal) fusion proteins. The same sequences fused to chloramphenicol acetyltransferase (CAT) or mouse dihydrofolate reductase (DHFR) react with high frequency when sera of acute malaria patients are analyzed in immunoblots. Antibodies from such sera crosslink, via their antigen binding sites, the beta-Gal fusions to the corresponding CAT or DHFR fusions adsorbed to a solid phase as demonstrated by the captured beta-Gal activity. The assay is highly specific, shows extremely low cut off values and should therefore be widely applicable.

Animals↗

[Captopril versus digoxin in the treatment of mild to moderately severe heart failure].

In a randomized and double-blind study of 116 patients with chronic heart failure (NYHA classes II or III) the effectiveness of captopril + hydrochlorothiazide (HCT) (group 1) and of digoxin + HCT (group 2) were compared. Treatment was effected for a 12-month period with a combination of 50 mg captopril (twice 25 mg daily, oral) and HCT, or 0.2 mg digoxin (twice 0.1 mg daily, oral) and HCT. In a pretreatment phase over 3-4 weeks the patients of group 1 were given an average HCT dose of 37.7 mg daily, whereas those of group 2 received 34.9 mg per day. At the end of the 12-month treatment period the patients in the captopril/HCT group had improved significantly more--by the criteria of echocardiographic intracardiac diameters, exercise tolerance and NYHA class--than those in the digoxin/HCT group. Change by a mean of one NYHA class had occurred in 61 patients (51.8%) of group 1 and in 47 (40.7%) of group 2 (P les than 0.01). These findings suggest that treatment of patients with mild to moderately severe chronic heart failure in sinus rhythm best be initiated with an angiotensin-converting enzyme inhibitor together with a diuretic rather than a digitalis-diuretic combination.

Blood Pressure↗

Development of the human immune response against the major surface protein (gp190) of Plasmodium falciparum.

The 190-kilodalton glycoprotein (gp190) of Plasmodium falciparum, the precursor of the major surface proteins of merozoites, is considered a promising candidate for a blood stage malaria vaccine. DNA sequences specific for the gp190 of the two isolates K1 and MAD20 were subcloned and expressed in Escherichia coli. The panel of fusion proteins obtained represents about 80% of the polymorphic sequences observed so far within various isolates of P. falciparum. Sera from individuals living in a malaria-endemic area of West Africa were tested in immunoblots against the gp190 fusion proteins, and antibody reactivity was mapped to defined regions of the gp190. Depending on the age of the individual and on the presence of parasites in the blood, distinct regions of gp190 were differentially recognized by the respective antibodies. Similarly, the analysis of sera from German patients with acute malaria revealed a distinct pattern. When grouped according to age and to parasitemia, the reactivity of the sera of people living in malaria-endemic areas may indicate a correlation between certain gp190 regions and protective immune response.

Animals↗

Epitopes recognized by human T cells map within the conserved part of the GP190 of P. falciparum.

In a study aimed at developing a vaccine against the asexual blood stages of Plasmodium falciparum, two T cell epitopes were identified within a nonpolymorphic region of gp190 of Plasmodium falciparum merozoites. The two epitopes, which were revealed by deletion analysis, stimulated human T cell clones. Peptides containing sequences of the epitopes stimulated the cloned T cells and peripheral blood mononuclear cells (PBMC) from malaria-infected individuals. Moreover, the T cell clones responded to 11 different Plasmodium falciparum isolates in culture, showing that the epitopes are recognized in native parasites.

Amino Acid Sequence↗

[Ergosterol as a measure of fungus growth in fodder. I. Ergosterol content of grain].

Ergosterol was determined as a chemical indicator of fungal biomass in wheat (w), barley (b), oats (o), and grain corn (c). In samples selected by microscopy and odour as an indicator of good mycological quality the following contents (mg/kg dry matter) were found: 1.96 +/- 0.72 (w), 2.43 +/- 0.82 (b), 2.42 +/- 1.4 (o), 0.61 +/- 0.37 (c). In cereals from farms in Baden-Württemberg (FRG) which were not selected by microscopy and odour 5.8 +/- 3.8 (w), 5.8 +/- 2.0 (b), 15.8 +/- 9.0 (o) mg/kg (year of harvest: 1984); and 3.5 +/- 1.9 (w), 3.9 +/- 1.4 (b), 9.9 +/- 3.6 (o) mg/kg (year of harvest: 1985) were found. Differences between years of harvest, between samples without and with selection, and between oats and the two other types of cereal are significant. Elevated ergosterol contents (as compared to those of selected samples) were found in 66 and 22% (w), 70 and 15% (b), 95 and 86% (o) of farm samples from 1984 and 1985, respectively. The more prolific mold growth in 1984 was mainly due to readier development of field fungi and can be explained by heavier rainfall. Almost all of the ergosterol contents described in literature for wheat and grain corn are in the range found in the present study.

Edible Grain↗

Influence of magnesium on blood pressure and the effect of nifedipine in rats.

The influence of long-term alterations in dietary magnesium intake on blood pressure and on the antihypertensive effect of the calcium antagonist nifedipine was investigated in normotensive Wistar-Kyoto (WKY) and in spontaneously hypertensive rats (SHR). The rats were fed a diet either high (1%), normal (0.1%), or low (0.01%) in magnesium for 12 weeks (WKY) and 20 weeks (SHR), respectively. Nifedipine was added to the diet for 4 weeks in concentrations of 300 and 1000 ppm. Each dose was given for 2 weeks. Plasma and intraerythrocytic concentrations of sodium, potassium, and magnesium were measured before and at the end of nifedipine treatment. Blood was obtained by cardiac puncture. In the WKY and SHR, blood pressure was not influenced by magnesium intake. The blood pressure-lowering effect of nifedipine was most pronounced on normal dietary magnesium and was significantly suppressed in the magnesium-deficient rats. Plasma and intracellular total magnesium concentrations were consistently increased during high and reduced during low dietary intake of the ion. Intracellular sodium concentration increased during magnesium deficiency and was normalized by nifedipine. The marked and long-term alterations in plasma and intracellular concentrations of magnesium did not influence arterial blood pressure levels in either the normotensive WKY or the SHR. Therefore, dietary magnesium intake does not appear to play an important role in long-term regulation of blood pressure in rats. However, magnesium depletion attenuates the blood pressure-lowering effect of nifedipine.

Animals↗

Gluconate accumulation and enzyme activities with extremely nitrogen-limited surface cultures of Aspergillus niger.

Batch cultures of Aspergillus niger grown from conidia on a medium with high C/N ratio accumulated gluconate from glucose with a yield of 57%. During almost the whole time of accumulation there was no net synthesis of total protein in the mycelium but the activity per flask and the specific activity of glucose oxidase (EC 1.1.3.4) in mycelial extracts increased whereas both values decreased for glucose dehydrogenase (EC 1.1.99.10) 'gluconate 6-phosphatase' (cf. EC 3.1.3.1, 3.1.3.2), gluconokinase (EC 2.7.1.12), glucose 6-phosphate and phosphogluconate dehydrogenases (EC 1.1.1.49, EC 1.1.1.44), phosphoglucomutase (EC 2.7.5.1), and most enzymes of the Embden-Meyerhof pathway and the tricarboxylic acid cycle. Gluconate dehydratase (EC 4.2.1.39), gluconate dehydrogenase (EC 1.1.99.3) and enzymes of the Entner-Doudoroff pathway could not be detected. By cycloheximide the increase of glucose oxidase activity was inhibited. It is concluded that the high yield of gluconate was due mainly to the net (de novo) synthesis of glucose oxidase which occurred during protein turnover after the exhaustion of the nitrogen source, and which was not accompanied by a net synthesis of the other enzymes investigated. Some gluconate may also have been formed by hydrolytic cleavage of gluconate 6-phosphate.

Aspergillus niger↗

Mineralocorticoid escape during kallikrein inhibition.

Kinins have been considered to be involved in the escape from the sodium retaining effects of mineralocorticoids. In a metabolic study in rats, the importance of the kallikrein-kinin system for sodium and potassium excretion was evaluated by aprotinin-induced kallikrein inhibition under basal conditions and during DOCA administration. Kallikrein inhibition was accompanied by a transient sodium retention. The escape from the sodium retaining effect of DOCA was not affected. However, the DOCA-induced potassium loss was enhanced. Kallikrein inhibition decreased urinary prostaglandin (PG) E2 and prevented the DOCA-induced rise in PGE2. Plasma renin activity was stimulated after 10 days of aprotinin administration. The kallikrein-kinin system is not an important mediator of the escape phenomenon but it may play a role in the regulation of sodium and potassium excretion.

Animals↗

Utilization of gluconate by Aspergillus niger. II. Enzymes of degradation pathways and main end products.

Aspergillus niger was grown from conidia on a medium with glucose as the source of carbon and potassium nitrate in non-limiting concentration as the source of nitrogen. After the exhaustion of glucose gluconate was added, this compound representing the almost only carbon source in the culture fluid at this time. Gluconate was used rapidly by the preformed mycelium, the main end-products of its metabolization being mycelial substance (including protein), CO2, and oxalate. In cell-free extracts from gluconate utilizing mycelia 8 enzymes of the Embden-Meyerhof (EM) pathway, 5 enzymes of the tricarboxylic acid (TCA) cycle, and an oxalate forming enzyme, oxaloacetate hydrolase (EC 3.7.1.1) were identified. The addition of fluoroacetate together with gluconate resulted in the accumulation of citrate, and in the inhibition of mycelial growth and of accumulation of oxalate. It is concluded that the EM pathway and the TCA cycle are involved in the formation of mycelial substance, CO2 and oxalate from gluconate. There is good correspondence between the rates of gluconate utilization and of oxalate accumulation which were observed immediately after the addition of gluconate and the in vitro activities of gluconokinase and oxaloacetate hydrolase, respectively, at this time.

Aspergillus niger↗

Hemodynamic, renal, and hormonal responses to changes in dietary potassium in normotensive and hypertensive man: long-term antihypertensive effect of potassium supplementation in essential hypertension.

The hemodynamic, hormonal, and renal responses to alterations in dietary potassium were studied in normotensive and hypertensive subjects. In a short-term study, nine normotensive and nine hypertensive young men received a normal diet and low potassium, high potassium, and high potassium/low sodium diets for 1 week, each. The long-term effect of potassium supplementation (normal diet plus 96 mmol KC1/d for 8 weeks) was evaluated in 17 patients with essential hypertension. Blood pressure did not change significantly during short-term alterations of potassium intake but decreased during long-term supplementation (from 152.2 +/- 3.5/99.6 +/- 1.9 mm Hg to 137.4 +/- 2.9/89.1 +/- 1.4 mm Hg). High dietary potassium induced a significant but transient natriuresis. Plasma potassium concentration was increased during long- but not during short-term high potassium intake. In contrast to plasma renin activity (PRA) and aldosterone, urinary kallikrein was consistently stimulated during long-term potassium supplementation. The plasma concentrations of adrenaline and noradrenaline were significantly higher in hypertensive than in normotensive subjects and were not markedly altered by the dietary changes. It is concluded that long- but not short-term potassium supplementation lowers blood pressure in patients with essential hypertension. The antihypertensive effect may be mediated by potassium-induced natriuresis, by a stimulation of Na-K-ATPase secondary to increased plasma potassium levels, and/or by a modulation of the renin-angiotensin-aldosterone, kallikrein-kinin, and sympathetic nervous systems.

Adult↗

Dissociation between kallikrein and aldosterone in Cushing's disease with periodic hormonogenesis.

It has been suggested that the renal kallikrein-kinin system is dependent on mineralocorticoid activity. This hypothesis was studied in a patient with cyclic Cushing's syndrome combined with cortisol suppressible, dexamethasone non-suppressible ACTH secretion. The 24-h urinary excretions of sodium, potassium, cortisol, active and inactive kallikrein, aldosterone, and prostaglandin E2 (PGE2) were studied during normal and excessive cortisol secretion and after bilateral adrenalectomy. Kallikrein, PGE2 and potassium rose during cortisol overproduction while aldosterone and sodium decreased. Kallikrein, PGE2 and potassium were positively related to cortisol excretion, whereas urinary aldosterone and sodium showed a negative relationship to cortisol. Kallikrein was inversely related to aldosterone. Excretion of inactive kallikrein followed closely the changes of active kallikrein. During cortisol excess, as in our patient, the mineralocorticoid activity of cortisol will exceed that of aldosterone. This suggests that the alterations in kallikrein, aldosterone and PGE2 during cortisol excess in the present study were due to the mineralocorticoid potency of the steroid.

Adrenalectomy↗

The influence of food intake on pharmacodynamics and plasma concentration of captopril.

The influence of food intake on the acute haemodynamic and humoral effects of captopril has been investigated. Eighteen patients with mild-to-moderate essential hypertension (diastolic blood pressure 95-115 mmHg) were treated in a randomized crossover study with a single oral dose of 25 mg captopril after 2 weeks of placebo. They were randomized to receive captopril either 1 h before or together with a standardized breakfast. Blood pressure, heart rate and plasma concentrations of angiotensin converting enzyme (ACE), angiotensin II (ANG II) and captopril were measured before and every 30 min up to 4 h after drug administration. Angiotensin converting enzyme was significantly more suppressed and plasma concentrations of captopril were significantly higher when the drug was given in the fasting patients. However, there was no significant difference in blood pressure reduction whether captopril was administered in the fasting patients or together with food. The results indicate that the antihypertensive efficacy of captopril is not markedly affected when the drug is administered with food.

Adult↗

Utilization of gluconate by Aspergillus niger. I. Enzymes of phosphorylating and nonphosphorylating pathways.

Gluconate which was produced in cultures of Aspergillus niger with glucose as the sole source of carbon, or which was added after exhaustion of glucose, was utilized by this mold. In cell-free extracts from gluconate degrading mycelia gluconokinase and five enzymes of the pentose phosphate pathway were identified. Enzymes of the Entner-Doudoroff pathway and of a modified (non-phosphorylating) Entner-Doudoroff system, as well as a gluconate dehydrogenase could not be detected. It is concluded that gluconate after its phosphorylation to 6-phosphogluconate is metabolized via the pentose phosphate pathway by the strain used.

Aspergillus niger↗

[Use of cytochemical methods for diagnosis in fungicide research].

Cytochemical localization of acid and alkaline phosphatases, cytochrom c-oxidase, peroxidases and catalase was carried out on Phytophthora infestans (Mont.) de By. and Mucor mucedo (L.) Fres. First results are obtained about the influence of sublethal dosages of fungicidal compounds on the demonstration of these enzymes in the electron-microscope.

Acid Phosphatase↗