Search PubMed⌕ Search

Biomedical subjects

K Becker

Publications and source records attributed to K Becker.

At least 271 records · Page 15Linked to original sources
PubMed1996

Rifabutin-associated anterior uveitis in patients infected with human immunodeficiency virus.

Iridocyclitis, arthralgia, and pseudojaundice have been identified as dose-dependent adverse effects in patients with acquired immunodeficiency syndrome (AIDS) who are treated orally with rifabutin for Mycobacterium avium intracellulare complex (MAC) infections. Nine episodes of acute anterior uveitis of varying severity ranging from mild iridocyclitis to anterior uveitis with fibrin or hypopyon, mimicking endogenous metastatic endophthalmitis, occurred in seven patients. At the time of presentation, all seven patients were receiving rifabutin at a dose ranging from 300 to 600 mg daily. Iridocyclitis was bilateral in four of seven patients, in two cases simultaneously and in two cases successively. Inflammation resolved rapidly on treatment with systemic and topical antibiotics, on corticosteroid therapy, and on discontinuation of rifabutin. In two cases of mild iridocyclitis, cessation of rifabutin alone led to resolution of the uveitis. The combination of rifabutin, clarithromycin, and fluconazole may increase the risk for anterior uveitis in patients with AIDS. All of our patients were treated with fluconazole, with clarithromycin, or with a combination of both substances in addition to rifabutin. Identification of rifabutin-induced uveitis is important because hypopyon uveitis in the immunocompromised patient generally evokes intensive and, sometimes, invasive ophthalmic and systemic workup and therapy. We suggest it to be sufficient for resolution of the inflammatory signs to discontinue rifabutin medication.

AIDS-Related Opportunistic Infections↗
PubMed1995

Inhibition of human glutathione reductase by S-nitrosoglutathione.

S-Nitrosoglutathione (GSNO) represents a major transport form in nitric oxide (NO) in biological systems. Since NO and GSNO have been shown to modulate the function of various proteins, we studied the influence of GSNO and other NO donors on human glutathione reductase (GR). Catalyzing the reaction NADPH+GSSG+H(+)-->NADP(+) + 2 GSH, the dimeric flavoprotein GR is the central enzyme of the glutathione redox metabolism. GSNO was found to inhibit crystalline erythrocyte GR in two ways: (a) as a reversible inhibitor GSNO is competitive with glutathione disulfide (GSSG), the Ki being appr. 0.5 mM; (b) as an irreversible inhibitor; after 1 h (3 h) incubation with 1 mM GSNO, GR (2.5 U/ml, representing intraerythrocytic concentrations) was inhibited by 70% (90%). This inhibition depended on the presence of NADPH and could not be reversed by dilution nor by reducing agents. Absorption spectra indicate that the charge-transfer interaction between Cys63 and the flavin is abolished by this modification. In a GR sample inhibited by 90% with GSNO, the Km values for the substrates GSSG and NADPH were not significantly changed nor did the modification induce oxidase activity of the enzyme. GSNO was found not to be a substrate in the forward reaction of GR. This implies that GSNO is not accounted for by methods which employ GR for determining total glutathione. Incubating isolated GR for 60 min with other NO donors, namely 1 mM sodium nitroprusside or 1 mM S-nitroso-N-acetyl-DL-penicillamine (SNAP), resulted in only 25% and 10% inhibition, respectively. This attests to a specific affinity of GSNO to the enzyme. GSNO inhibition patterns comparable to purified authentic GR were obtained for purified recombinant GR, a GR mutant lacking the 15 N-terminal amino acids including Cys2, and for the enzyme present in diluted fresh haemolysates (0.02 U/ml); in concentrated haemolysates the inhibition was less pronounced. GR of intact erythrocytes was not affected when exposed to GSNO in the medium. Our results suggest that the irreversible inhibition of GR by GSNO involves nitrosylation of Cys63 and/or Cys58 at the catalytic site of the enzyme. To further investigate the mechanism of inactivation we have crystallized GSNO-modified GR for X-ray diffraction analysis.

Binding Sites↗
PubMed1995

Interaction of peptides derived from the Fas ligand with the Fyn-SH3 domain.

Interaction of the widely expressed Fas with its membrane-bound ligand (FasL) leads to rapid cell death via apoptosis. To avoid pathological tissue damage, the activity of FasL requires tight regulation. Here, we report that the Src homology 3 (SH3) domain of Fyn binds to the proline-rich cytoplasmic region of FasL. Binding of the SH3 domain occurs between amino acid residues 44-71 which contains several potential SH3 interaction sites. This binding is specific, as SH3 domains of Lck, Grb2 and ras-GAP bind only weakly or not at all. We suggest that FasL activity may be modulated by SH3 domains of the src-like Fyn kinase.

Amino Acid Sequence↗
PubMed1995

[Autonomic failure as the cause of vertigo and syncope].

BACKGROUND: Vertigo and syncope often occur during orthostatic conditions. A possible cause is asympathicotonic dysregulation with a fall of blood pressure and no increase in heart rate. After the exclusion of secondary disturbances of autonomic innervation. g. in diabetes mellitus, and pharmacological side effects, e.g. tricyclic antidepressants, primary reasons must be considered. We present 2 cases of primary autonomic failure. PATIENTS: Patient 1 had Parkinson-syndrome, impaired bladder function and orthostatic dysregulation with a maximal drop of blood pressure to 60/40 mm Hg. Patient 2 showed orthostatic dysregulation with a minimal blood pressure of 70/30 mm Hg without further symptoms, in a tilt table examination catecholamines were measured during orthostatic conditions. Patient 1 had normal, and patient 2 very low resting catecholamine plasma levels. Neither patient reacted with a rise of plasma catecholamines when tilted to an upright position. These findings are diagnostic of multiple system atrophy (MSA) in patient 1 and pure autonomic failure (PAF) in patient 2. DISCUSSION: In PAP only dysautonomic symptoms are found. It has a favourable prognosis. MSA consists of an autonomic dysregulation in combination with parkinsonism, cerebellary and bulbar symptoms, prognosis quo ad vitam is poor. Diagnosis is often established by a tilt table examination and radiology findings, and is often late. Treatment of both diseases consists of pharmacological, e.g. fludrocortisone, vasopressin analogues and ergotamine tartrate as well as non-pharmacological blood pressure stabilizing measures.

Adult↗
PubMed1995

Comparative sperm chromatin structure assay measurements on epiillumination and orthogonal axes flow cytometers.

The sperm chromatin structure assay (SCSA) measures the susceptibility of sperm nuclear DNA to acid-induced denaturation in situ, and was developed on two Ortho flow cytometers, an FC200 [Becton Dickinson Immunocytometry Systems (BDIS), Westwood, MA] and a Cytofluorograf 30 (BDIS), both having orthogonal axes of fluorochrome excitation, emission, and sample flow. Sperm cells are first treated with a pH 1.4 buffer to denature DNA in situ and then stained with the metachromatic dye acridine orange (AO). The metachromatic fluorescence measured reflects relative amounts of denatured (red fluorescence) and native (green fluorescence) DNA present per cell. The extent of DNA denaturation is quantified by the calculated parameter alpha t [alpha t = red/(red+green) fluorescence]. Alpha t variables important for correlations with fertility and toxicant-induced chromatin damage include mean (X alpha t), standard deviation (SD alpha t), and cells outside the main population (COMP alpha t). Mean green fluorescence intensity is an important measure for DNA content and/or degree of sperm chromatin condensation. This study showed that the SCSA can be successfully run on two epiillumination-type instruments, an Ortho ICP22A (BDIS, San Jose, CA) and Skatron Argus (Tranby, Norway), and two additional orthogonal axes instruments, a Becton Dickinson FACScan (BDIS) and a Coulter Elite (Coulter Corporation, Hialeah, FL). Epiillumination instruments produced a different fluorescence distribution than orthogonal instruments, but the resulting alpha t values showed strong conformity and interpretation of results was the same. SCSA values obtained on the Coulter Elite were most similar to the Cytofluorograf 30; the FACScan green fluorescence distribution was narrower and allowed resolution of cell doublets.(ABSTRACT TRUNCATED AT 250 WORDS)

Acridine Orange↗
PubMed1995

C1840-T mutation in the human skeletal muscle ryanodine receptor gene: frequency in northern German families susceptible to malignant hyperthermia and the relationship to in vitro contracture response.

In swine, a point mutation in the ryanodine receptor gene can account for all cases of malignant hyperthermia (MH). The frequency of a corresponding mutation in humans (C1840-T) and its relationship to the in vitro contracture profile is unknown. We screened 192 patients from 28 unrelated northern German families for the C1840-T mutation in the human ryanodine receptor gene and tested for MH susceptibility using the in vitro contracture test (IVCT) according to the European MH Protocol. In our patients 106 revealed MH susceptible (MHS), 56 MH nonsusceptible and 30 MH equivocal status following IVCT. In each family one or two individuals had developed clinical signs of MH or a MH crisis. All of these patients were classified MHS. The C1840-T mutation was found in 2 of 28 families (7.1%). All eight individuals of the two families characterized by this mutation revealed MHS status following IVCT. The thresholds for halothane- and caffeine-induced contractures as well as the contracture profiles following cumulative (0.4-10.0 mumol/l every 3 min) and bolus (10 mumol/l) administration of ryanodine were found to be similar in MHS patients with and without the C1840-T mutation. In conclusion, the C1840-T mutation in the human ryanodine receptor gene is a rare abnormality in MHS families. Similar contracture profiles in the presence and absence of this mutation might imply no major functional role with respect to the contracture response. At present, molecular genetic analysis cannot replace IVCT to discover MH susceptibility in humans.

Adolescent↗
PubMed1995

Plasmodium falciparum glutathione reductase exhibits sequence similarities with the human host enzyme in the core structure but differs at the ligand-binding sites.

The homodimeric flavoenzyme glutathione reductase (GR) which catalyzes the reduction of glutathione disulfide is a cornerstone of the malaria parasite antioxidant defense and repair mechanisms. Here we report on the identification of the GR gene from Plasmodium falciparum. A 1.4-kb fragment of the gene was amplified by polymerase chain reaction (PCR). Using this PCR fragment as a probe a full length cDNA clone (2085 bp) was isolated from a P. falciparum gametocyte library. The deduced amino acid sequence of 541 residues shows an overall identity of 35% when compared to the human enzyme. Most amino acids of known function are identical. However, notable differences between human and parasite protein occur in the glutathione-binding pocket (for instance, Glu374 instead of the expected basic residue) and at the intersubunit contact area. These regions are of particular interest since they represent binding sites of known GR inhibitors. Consequently, parasite GR can serve as a target structure for the design of antimalarial drugs.

Amino Acid Sequence↗
PubMed1995

Influence of ambient temperature on content and composition of brain gangliosides in vertebrates.

The concentration and composition of brain gangliosides have been comparatively investigated by means of one- and two-dimensional high performance thin layer chromatography in several European fish species exhibiting a pronounced capacity for thermal adaptation. The values were compared with those of tropical and Antarctic fish as well as with homeo- and heterothermic mammals. The relative proportion of higher sialylated (more polar) ganglioside fractions was elevated in brains of fish (a) whose habitat was naturally cold or (b) that had been experimentally or seasonally adapted to a cold versus a warm habitat. Furthermore, in adaptation to the cold, more alkali-labile brain ganglioside fractions were found with the following sequence: Antarctic fish (53-67%), cold acclimated fish (45-51%), warm acclimated fish (38-44%), tropical species (< 35%), hamsters in torpor (9%), active hamsters (4%) and pig (3%). These results indicate a possible mechanism at a molecular level to keep the neuronal membrane functional, even under changing temperature conditions.

Adaptation, Physiological↗
PubMed1995

Glutathione and association antioxidant systems in protein energy malnutrition: results of a study in Nigeria.

Marasmus and kwashiorkor are manifestations of protein energy malnutrition. The pathophysiology of these disorders is poorly understood. We studied a number of blood antioxidants [glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR) and its cofactor flavin adenine dinucleotide (FAD), the tripeptide glutathione as the major nonprotein thiol], serum albumin, and retinol-binding protein in 12 children suffering from kwashiorkor with all classical symptoms, in 13 patients with clinically severe marasmus, in 19 marasmic but active children, and in 23 controls. Significant changes were observed for erythrocyte glutathione and correspondingly for nonprotein thiols in whole blood (0.72 +/- 0.29 mM thiols in controls, 0.50 +/- 0.22 mM in marasmus, 0.35 +/- 0.23 mM in severe marasmus, and 0.22 +/- 0.13 mM in kwashiorkor). These differences were paralleled by a decrease in serum albumin concentration so that the molar ratio of nonprotein thiols/albumin had an average value of approximately 1.5 in all groups. The erythrocyte glutathione-reducing system, represented by G6PDH and glutathione reductase, showed only slight differences among the four groups of children; the supposition that kwashiorkor occurs predominantly in children with aberrant G6PDH could not be substantiated. Unexpectedly, erythrocyte FAD, an index of riboflavin status, was normal in most malnourished patients. Discussed is the prospect of administering glutathione in kwashiorkor patients.

Blood Proteins↗
PubMed1995

PAF effects on eicosanoid release in neonatal rat cardiomyocytes.

The aim of this study was to find out whether, in neonatal rat cardiomyocytes, platelet-activating factor (PAF) can stimulate eicosanoid formation. For this purpose neonatal cardiomyocytes were incubated for 60 min at 37 degrees C in HANKS buffer with PAF (10-1000 nM), and the eicosanoids thromboxane A2 (TXA2) and prostacyclin (PGI2) were assessed in the supernatant as TXB2 and 6-keto-PGF1 alpha, respectively, by an enzyme immunoassay. PAF caused concentration-dependent release of PGI2; TXA2, however, was significantly released only at the highest concentration of PAF (1000 nM). Acetylsalicylic acid (556 microM) and the PAF antagonist WEB 2086 (10 microM) significantly attenuated PAF-induced eicosanoid formation. We conclude that in neonatal rat cardiomyocytes PAF can induce eicosanoid formation and this effect is brought about by activation of a specific PAF receptor.

Animals↗
PubMed1995

Formation of complexes between polyvinyl pyrrolidones or polyethylene glycols and tannins, and their implication in gas production and true digestibility in in vitro techniques.

Various tannin-complexing agents have been used to study the potential adverse effects of tannins on rumen metabolism. Using a method based on turbidity formation, the binding of various tannin-complexing agents (polyvinyl polypyrrolidone (PVPP), polyethylene glycol (PEG) of molecular weights 2000 to 35,000, and polyvinyl pyrrolidone (PVP) of molecular weight 10,000, 40,000 and 360,000) to tannins (tannic acid, purified tannins from quebracho (Aspidosperma quebracho) and leaves of trees and shrubs (Acioa barteri, Dichostachys cinerea, Guiera senegalensis, Piliostigma reticulatum)) was investigated at different pH values. The binding of all the tannins with PVPP was highest at pH 3-4 and lowest at pH 7. For all the pH range (3-7) studied, the binding of PEG was higher than that of PVP. For all the tannins except tannic acid, the binding to PVP was the same from pH 4.7 to 7. Similar results were observed for the PEG of molecular weight 6000 or higher for all the tannins except quebracho tannins for which the binding increased as the pH increased from 3 to 7. The binding with PEG 2000 decreased to a greater extent as the pH reached near neutral and for PEG 4000 this decrease was slightly lower. Addition of these tannin-complexing agents to the in vitro gas system resulted in higher gas production from tannin-rich feeds (increase varied from 0 to 135%). The PEG were the most effective followed by PVP and PVPP. The PEG 35,000 was least effective. The efficiency of other PEG was similar. The PEG 6000 was preferred to PEG 2000 or 4000 as its binding to tannins was higher at near neutral pH values. The gas production increased with an increase in the amount of PEG 6000 up to 0.6 g/40 ml rumen-fluid-containing medium containing 0.5 g tannin-rich feed, beyond which no increase was observed. The percentage increase in gas value at 24 h fermentation correlated significantly with tannin values, the highest correlation (r 0.95) being with protein precipitation capacity of tannins. The increase in gas production was associated with higher production of short-chain fatty acids with little change in their molar proportions, suggesting an increase in organic matter digestibility by inclusion of the PEG in tannin-rich feeds. However, apparent and true digestibilities were lower on addition of the PEG, due to the presence of PEG-tannin complexes in the residues. The use of this bioassay (percentage increase in gas production in the presence of PEG 6000) along with other tannin assays would provide a better insight into the nutritional significance of tannins.

Animals↗
PubMed1995

Fuzzy logic and control: principal approach and potential applications in medicine.

During the last few years intelligent machines appeared in nearly all technical areas, such as consumer electronics, robotics, and industrial control systems. There are for example washing machines that work very effectively, need comparably less power than in the past, and have short execution times because they adjust their washing cycles to each set of clothes and change their washing strategies as the clothes become clean. These intelligent systems are based on fuzzy control strategies, i.e., common sense rules are used to describe a system's behavior instead of complex mathematical models. We have applied this new technology to control problems as well as to reasoning problems in biomedical engineering where appropriate mathematical models could not be built due to the complexity of the problem. After a short introduction to the concepts of fuzzy logic two approaches in the field are described: a fuzzy control strategy for the pump rate adjustment of a novel total artificial heart and an intelligent alarm system based on fuzzy inference which supports the anesthetist in monitoring and evaluating the hemodynamic state of a patient undergoing cardiac surgery. These examples indicate the inherent reliability and stability of this technique in the field of complex dynamic systems. Such properties are highly significant especially in medical applications.

Anesthesia↗
PubMed1995

Fuzzy control concept for a total artificial heart.

The development of an electromechanically driven total artificial heart (Helmholtz-TAH) was initiated in 1990. Anatomical fitting, biocompatibility, and automatic physiologic adaptation of pump output are the basic requirements that characterize the overall TAH concept. For evaluation of these features, a TAH labtype was developed. It provides most features of the conceptual artificial heart and supports in vitro testing of energy conversion, pump behavior, structural parts, sensors, and control concepts. A fuzzy controller has been implemented for adaptation of the pump rate to body perfusion demand by left pump chamber filling detection. This controller will be an important element of a future extensive TAH control system. The implementation is supported by a professional fuzzy control development tool that allows on-line and real time optimization of control strategies for dynamic processes. The first experiments proved the feasibility and the advantages of this fuzzy control concept. The first in vitro test results are presented.

Fuzzy Logic↗
PubMed1995

Polyunsaturated fatty acids in erythrocyte and plasma lipids of children with severe protein-energy malnutrition.

The fatty acid composition of plasma cholesterol esters, plasma phospholipids, erythrocyte phosphatidylcholine and erythrocyte phosphatidylethanolamine was investigated in severely malnourished Nigerian children with kwashiorkor (n = 12) and marasmus (n = 32). Normally nourished children from the same area (n = 23) served as controls. The malnourished children showed a significant reduction of highly polyunsaturated fatty acids in cholesterol esters, phospholipids and phosphatidylcholine. No differences between the groups were found in erythrocyte phosphatidylethanolamine. Children with kwashiorkor had lower levels of linoleic acid metabolites and docosahexaenoic acid than marasmic children. The results suggest that the kwashiorkor syndrome is associated with impaired desaturation and elongation of PUFA and/or increased lipid peroxidation.

Arachidonic Acid↗