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Biomedical subjects

G Mayer

Publications and source records attributed to G Mayer.

At least 19 recordsLinked to original sources

Streptomycin biosynthesis and its regulation in Streptomycetes.

New insights into the gene orders, structures, evolution, and functions of streptomycin (Sm) biosynthetic genes (str) were gained via hybridization studies, determination of nucleotide sequences, and measurement of expression in the str gene clusters of Streptomyces griseus and S. glaucescens. Both str clusters showed considerable divergence in macro and micro structure. Genes putatively involved in pathways leading to the (dihydro-)streptose and N-methyl-L-glucosamine moieties of Sm were identified. Additional regulatory elements, such as gene strS and conserved TTA codons in the N-terminal sections of reading frames, are reported. Evidences for the involvement of physiological state, signal transduction, and activators in the control of Sm production are presented.

Bacterial Proteins

[Clinical and immune hematologic problems in prenatal prevention of Rhesus sensitization].

Various studies have provided impressive evidence of the efficacy of antenatally administered anti-D in the prevention of rhesus (D) alloimmunisation in rhesus-negative women. However, possible clinical and immunohaematological problems associated with this prophylactic therapy have received little attention. We describe perinatal and immunohaematological problems, which occurred in four cases after antenatal rhesus prophylaxis. Classical immunohaematological techniques were employed, to detect and specify irregular red cell antibodies. It was found, that the antenatal administration of anti-D could mask sensitization to other red cell antigens or the production of maternal immune anti-D antibodies later in pregnancy. A further problem encountered was that of neonates with a positive direct Coombs' test (the uncertainty in the individual case being, whether this is a result of the antenatal administration of anti-D) and marked hyperbilirubinaemia. Antenatal immunoprophylaxis for rhesus disease can give rise to immunohaematological and clinical findings, of which the interpretation is extremely difficult and requires intensive cooperation between the obstetrician, neonatologist, and haematologist/clinical biochemist.

Adult

Isoagglutinins following ABO-incompatible bone marrow transplantation.

Isoagglutinins were investigated following ABO-incompatible bone marrow transplantation. In major incompatibility anti-A tends to require more time to disappear than anti-B. Correspondingly, A erythrocytes require more time to become demonstrable. There is no such difference in major plus minor incompatibility. In minor incompatibility, isoagglutinins against the recipient blood group may be produced early after bone marrow transplantation, which then give way to a possibly lifelong tolerance for the recipient's old blood group.

ABO Blood-Group System

Angiotensin II receptor blockade limits glomerular injury in rats with reduced renal mass.

The effects of angiotensin II (AII) blockade were compared with the effects of angiotensin converting enzyme inhibition in rats with reduced nephron number. Rats were subjected to five-sixths renal ablation and divided into four groups with similar values for blood pressure and serum creatinine after 2 wk. Group 1 then served as untreated controls, while group 2 received the AII receptor antagonist MK954 (which has previously been designated DuP753), group 3 received the converting enzyme inhibitor enalapril, and group 4 received a combination of reserpine, hydralazine, and hydrochlorothiazide. Micropuncture and morphologic studies were performed 10 wk later. Converting enzyme inhibition, AII receptor blockade, and the combination regimen were equally effective in reversing systemic hypertension (time-averaged systolic blood pressure: group 1, 185 +/- 5 mmHg; group 2, 125 +/- 2 mmHg; group 3, 127 +/- 2 mmHg; group 4, 117 +/- 4 mmHg). Micropuncture studies showed that glomerular transcapillary pressure was reduced significantly by converting enzyme inhibition and by AII blockade but not by the combination regimen (delta P: group 1, 49 +/- 1 mmHg; group 2, 42 +/- 1 mmHg; group 3, 40 +/- 2 mmHg, group 4, 47 +/- 1 mmHg). Reduction of systemic blood pressure was associated with the development of markedly less proteinuria and segmental glomerular sclerosis in rats receiving enalapril and MK954 but not in rats receiving the combination regimen (prevalence of glomerular sclerotic lesions: group 1, 41 +/- 4%; group 2, 9 +/- 1%; group 3, 9 +/- 1%; group 4, 33 +/- 6%). These results indicate that the effects of converting enzyme inhibition on remnant glomerular function and structure depend on reduction in AII activity and are not attributable simply to normalization of systemic blood pressure.

Angiotensin II

Voltage-dependent calcium current in human decidual cells and its relation to prolactin secretion.

Human decidual cells synthesize and release decidual PRL (dPRL) immunologically and biochemically identical to human pituitary PRL. However, stimulators and inhibitors of PRL secretion such as TRH, bromocriptine or dopamine have no effect on dPRL release. The evidence for the involvement of Ca2+ in dPRL release is based on contradictory or unclear data. Since little is known about Ca2+ movement in human decidual cells we studied the membrane Ca2+ conductance of cultured decidual cells using the patch-clamp technique in the whole-cell configuration. We report the existence of Ca(2+)-dependent action potentials triggered by hyperpolarizing or depolarizing pulses and blocked by cobalt (Co2+; 5 mM). Spontaneous action potentials were observed in the cell-attached mode and found also to be Co(2+)-sensitive. A tetrodotoxin-insensitive and Ca(2+)-dependent rapidly inactivating inward current was investigated in voltage clamp. Its activation threshold was between -60 and -45 mV. Indo-1 measurements of free intracellular Ca2+ concentrations ([Ca2+]i, 169 +/- 14 nM and 141 +/- 8 nM in short-term culture vs. 149 +/- 5 nM in cells cultured for 3-6 days) showed that decidual cells have spontaneous transient fluctuations of [Ca2+]i and that [Ca2+]i was decreased by Ca2+ channel blockers. The existence of Ca2+ movements in decidual cells in culture is thus demonstrated. The occurrence of action potentials in decidual cells derived from fibroblasts, reputed to be inexitable cells, is an interesting biological observation. However, Ca2+ is not involved in the short-term release of PRL by decidual cells, and its effects on long-term secretion still requires further investigation.

Action Potentials

[Isoagglutinins after bone marrow transplantation with minor ABO incompatibility].

Sera of 22 patients after BMT with blood group change from A to 0 were investigated. Early after BMT 59% of the patients developed a temporary anti-A whereas late after BMT none of the patients tested showed isoagglutinins against A even though the red blood cells were of type 0 and anti-B was present. The onset of these anti-A isoagglutinins correlated with production of leukocytes by the donor BM and is regarded as a sign of GvHR. Late after BMT a permanent immunological tolerance to the A antigen of the recipients' old blood group seems to exist.

ABO Blood-Group System

Biocompatibility of high-flux membranes.

Standard dialysis with cuprophane membranes is known to stimulate the immune system. As a result of activation of macrophages various interleukins and tumor necrosis factor (TNF) are secreted, presenting further evidence of the poor biocompatibility of cuprophane. We investigated the immunogenic properties of three modern high-flux membranes. Seven patients were studied during hemodiafiltration sessions using either a polysulfone (F60, Fresenius), a polymethylmetacrylate (BK 2.1, Toray) or a cellulose triacetate (FB-210 U, Nipro) dialyzer in a hemodiafiltration procedure. Serial measurements were made during each treatment of interleukin-1 beta (II-1 beta), TNF, soluble IL-2 receptor (sII-2r), soluble CD4 (sCD4), soluble CD8 (sCD8), interferon gamma (IFNg) and neopterin. In contrast to the known increase of IL-1 beta, IL-2r and TNF with cuprophane membranes, none of the modern high-flux dialyzers stimulated the production of these factors. Significant decreases of neopterin and sCD4 were observed. IFNg and sCD8 did not change significantly. Our results suggest that the modern high-flux dialyzers are non-immunogenic, and thus provide further evidence of the superior biocompatibility of synthetic or semisynthetic membranes over the conventional cuprophane.

Aged

Synthesis of different pectinases by filamentous growing A. niger mutants.

Mutants of A. niger K 69/26, prepared by multistep mutagenesis (UV, MNNG, heating) have been screened for pectinase activities. Mutants with altered levels of certain pectinases, such as endo- and exopolygalacturonase (PG vis, red), pectinesterase (PE) and pectinlyase (PL), were isolated. The enzyme activities of the best mutants M 1348/126 were increased 2-3-fold compared to the parent strain after a 6-d cultivation of filamentous mycelium on a shaker. Further mutagenesis of mutants with decreased pectinase activities (e.g. Se3) produced revertants. PG (vis) synthesis of revertant Se5 was increased 1.7 times compared to the control strain K 69/26. Independent of these increased rates, the general level of pectinase activities synthesized by the filamentous mycelium of A. niger mutants amounts to about 10-20% compared with those produced by aggregated mycelium. It appears that the enzyme synthesis related to mycelium structure is independent of the mechanism which regulates the level of pectinase synthesis within a specific morphological structure.

Aspergillus niger

Hemodynamic effects of partial correction of chronic anemia by recombinant human erythropoietin in patients on dialysis.

Eighteen patients on chronic hemodialysis with renal anemia were treated with recombinant human erythropoietin (r-HuEPO). Hemodynamic parameters in the resting state were determined before and after successful treatment. Posttreatment cardiac index was decreased (3.3 v 2.8 L/min/m2), whereas diastolic blood pressure (72 v 79 mm Hg) and calculated peripheral resistance (2,230 v 2,860 dyne.cm.s-5) were increased significantly when compared with the pretreatment period. We conclude from our study that the increase of blood pressure as seen in patients on dialysis, who are effectively treated with r-HuEPO, is due to an increase in peripheral resistance. This increase overrules the decrease of cardiac index and might well be a result of peripheral vasoconstriction due to improved oxygen availability.

Adult

[Active immunotherapy of habitual abortion: is the danger greater than the therapeutic gain?].

Active immunotherapy is widely employed in the treatment of patients with habitual abortion, but it is comparable to the transfusion of blood or blood components with respect to possible complications such as undesirable immune responses and the possibility of transmitting infectious diseases. In fact, immunization with lymphocytes carries a greater risk of infection with cytomegalovirus than does transfusion of erythrocytes or platelets, a fact of particular relevance, since it represents a potential risk to the child. In addition, irregular antibodies to erythrocytes or platelets may be induced, which may have a harmful effect on both the mother and the child. The subsequent formation of autoantibodies and antibodies against cardiolipin in patients subjected to active immunotherapy has only recently been described. The significance of these and other possible immune responses is by no means clear, so that further investigation of the immunological side effects is urgently required. Active immunotherapy for habitual abortion demands strict medical indication, since the mechanism by which it protects the pregnancy has not been elucidated, and controlled studies have yielded differing results concerning therapeutic success. These factors must be taken into account when affected couples are counselled. The possible complications should be carefully weighed against the anticipated effects, since no vital indication exists in the case of habitual abortion, unlike most situations where the transfusion of blood products is contemplated.

Abortion, Habitual

Determination of cyclosporine by a competitive binding assay with cyclophilin.

A competitive protein-binding assay for cyclosporine based on use of the intracellular cyclosporine-binding protein cyclophilin (CYP) was used to measure cyclosporin A (CsA) and its bioactive metabolites in whole blood. CYP from cytoplasmic extracts or erythrocyte lysates was applied in the binding assay with use of [3H]CsA as tracer and charcoal adsorption for separating bound from free tracer. Binding affinities of various CsA analogs and metabolites correlated well with their reported in vitro immunosuppressive activities. The assay detected as little CsA as 50 micrograms/L (1 g = 0.832 mmol of CsA), analytical recovery was greater than 80%, and CVs were less than 8% for intra-assay and less than 11% for interassay precision in the range of 150-1000 micrograms/L. We used this assay to measure CsA concentrations in blood and compared the results with those measured by HPLC or by CsA-specific (monoclonal) and CsA-nonspecific (polyclonal) radioimmunoassays. Binding assay results were, in nearly all cases, less than those measured by the nonspecific RIA and frequently greater than 20% above the values determined by the CsA-specific assays. Individual patients had pronounced differences in the relative proportions of CsA, CYP-binding (bioactive) metabolites, and cross-reacting CsA metabolites. Because the presence of bioactive metabolites may considerably contribute to the immunosuppressive activity of CsA, we consider the binding assay clinically useful for measuring CsA in biological fluids.

Administration, Oral

Digital vascular reactivity in patients on haemodialysis treated with human recombinant erythropoietin.

Digital vascular reactivity was determined in 12 normotensive patients on chronic hemodialysis without a history of Raynaud's phenomenon before and after partial correction of anaemia with human recombinant erythropoietin (rHuEPO): apparent finger systolic pressures and finger skin temperatures were recorded at rest, after local cooling, and following 5 minutes rewarming time. Finger systolic pressures remained constant during the whole test, pre and post rHuEPO therapy. The decrease in finger skin temperatures after cold provocation as well as the rewarming behaviour after cooling were normal in both examinations. The present data indicate that treatment with EPO does not interfere with digital arterial reactivity in normotensive patients on haemodialysis.

Adult

Effects of changes in peripheral and cerebral glucose metabolism on locomotor activity, learning and memory in adult male rats.

Interactions of glucose and cognitive function have been reported both in the presence of elevated arterial blood glucose levels and with decreased cerebral glucose metabolism. In order to test the peripheral vs. central effects of this phenomenon, we induced irreversible hyperglycemia and depression of cerebral glucose metabolism in separate designs by means of either intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of streptozotocin (STZ), which is known to damage insulin-producing cells. Behavioral functions, such as locomotor activity, learning, and memory, were investigated under these different conditions. IP treatment with STZ decreased locomotor activity and increased initial step-through latencies on the passive avoidance test. No effects of elevated arterial blood glucose levels on retention of passive avoidance learning checked at 24 h and 144 h after training were observed. I.c.v. treatment of STZ increased the rate of locomotor activity and impaired retention in the passive avoidance test at 24 h, without further forgetfulness at 144 h. This finding may indicate disturbed acquisition and/or consolidation of memory, which may remain impaired but at a constant level, without further deterioration. Enhanced motor activity and impaired acquisition of passive avoidance learning without further impairment have also been reported as a characteristical behavioral pattern after disruption of the cholinergic system. It is therefore postulated that the observed behavioral abnormalities consequent on an impairment of cerebral glucose metabolism may be suggestive of cholinergic dysfunction.

Animals

[The significance of erythropoietin for nephrology].

The analysis of the structure of erythropoietin and the subsequent production of recombinant human erythropoietin opened a new era in the understanding of the pathogenesis and therapy of renal anaemia. From the diagnostic point of view sufficiently accurate radioimmunoassays are currently available to throw new light on the pathogenesis of renal anaemia, and enable pharmacokinetic studies of the recombinant hormone to be carried on. For the first time a causal therapy is available for renal anaemia. The following review summarizes the consequences of these innovations on the different aspects of nephrology.

Anemia

[Determination and occurrence of zearalenone in cereals and mixed feeds].

An HPLC method with fluorescence detection is described for the determination of zearalenone in cereals and mixed feeds. Samples are extracted with chloroform at low pH and cleaned up using an acid-base treatment or gel-permeation chromatography (GPC). Mixed feeds must additionally be cleaned up with extraction columns, because of their different compositions. With the extraction procedure described and GPC clean-up, ochratoxin A can be determined simultaneously. The limit of determination for zearalenone is 2.5 micrograms/kg. The average recovery rate, tested in the range 3.5 to 85 micrograms/kg was found to be 97%. Using this method, 91 samples of cereals and mixed feeds, harvested in 1989, were examined. The contamination rate was 42%. The results are discussed.

Animal Feed

[ABO-major incompatible bone marrow transplantation. Experiences with a simple method for the preparation of erythrocyte-poor bone marrow].

The special preparative technique presented here, used in ABO-major-incompatible BMTs, enables an excellent stem cell yield (mean: 94%), reducing the number of incompatible RBCs to a minimum (mean: 3.5 ml packed RBCs). This easy procedure is performed by simple mechanical means, using a pair of opposed, specially formed yaws and a modification of a common blood-collecting bag.

ABO Blood-Group System