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Biomedical subjects

K Becker

Publications and source records attributed to K Becker.

At least 37 records · Page 2Linked to original sources

[Experimental animal studies for the detection of circulating Toxoplasma antigens].

Rabbits and mice were infected by Toxoplasma gondii (RH and HanR) and Hammondia hammondi. An enzyme immunoassay with monoclonal antibodies was used to reveal circulating Toxoplasma antigens. They were found only in mice and rabbits that had been infected by the cyst-forming strain Toxoplasma HanR. In mice infected by Hammondia hammondi low antibodies titres were found that showed a cross-reaction with Toxoplasma. The enzyme immunoassay for evidence of Toxoplasma antigens demonstrated a negative reaction in these animals.

Animals

[Analgesic nephropathy (AN) with special reference to capillary sclerosis. A multicenter study from the former East Germany].

The incidence of capillary sclerosis in the mucosa of the upper urinary tract was beyond expectation, according to a multicenter study conducted at 11 pathological institutes in all regions of the former GDR from which the following more specific findings were obtained: Capillary sclerosis was recorded primarily from women (1.4:1) in 3.6% of 3,929 autopsy cases (minimum age being 40 years). This result has close to the outcome of a study conducted in Basle, Switzerland, though highest severity (0.33%) and the complete morphological picture of analgesic nephropathy (0.54%) were clearly less frequent, as compared to the above Swiss findings. No reliable conclusion can as yet be drawn regarding the infrequent case of renal pelvis carcinoma. Epidemiological and clinical studies are likely to suggest that an increase in findings might be expected in this part of Germany and might be aetiologically attributable to abuse of analgesics.

Adult

Protein-chemical standardization of the erythrocyte glutathione reductase activation test (EGRAC test). Application to hypothyroidism.

The erythrocyte glutathione reductase activation coefficient (EGRAC) is an index of riboflavin deficiency or, more exactly, of FAD deficiency in man. In this report a sensitive version of the EGRAC test is introduced that is based on the molecular properties of glutathione reductase and its FAD-free apoenzyme. The hemoglobin concentration of the blood sample can be estimated simultaneously using the spectrophotometric absorption at 340 nm. - The method was tested for 33 thyroidectomized patients in comparison with a euthyroid control group. From the average EGRAC values (1.40 vs. 1.22) it was deduced that the average free FAD level was approximately 2 times lower for the patients' than for the control group. Discussed is the role of the EGRAC test in hormonal and nutritional disorders.

Adult

Contact sites between inner and outer membranes: structure and role in protein translocation into the mitochondria.

Contact sites between both mitochondrial membranes play a predominant role in the transport of nuclear-coded precursor proteins into mitochondria. The characterization of contact sites was greatly advanced by the reversible accumulation of precursor proteins in transit (translocation intermediates). It was found that the sites are saturable, apparently contain proteinaceous components and mediate extensive unfolding of the polypeptide chain in translocation. Some components of mitochondrial contact sites are currently being identified.

Animals

Flavin analogs with antimalarial activity as glutathione reductase inhibitors.

10-(4'-Chlorophenyl)-3-methylflavin has antimalarial activity in vitro and in vivo (Cowden et al., J Med Chem 31: 799, 1988). This flavin analog and two of its derivatives were found to inhibit the antioxidant flavoenzyme glutathione reductase from human erythrocytes in its isolated form as well as in hemolysates. The mixed-type inhibition was completely reversible, the Ki-values being of the order of 1 microM. Surprisingly, the drugs were not competitive with FAD, but with GSSG, one of the enzyme's substrates. Malaria parasite glutathione reductase, extracted from Plasmodium falciparum, could also be inhibited by the compounds. Studies on the effects of the substances on P. falciparum in vitro, which were demonstrated morphologically and by growth inhibition, confirmed previous observations with 10-(4'-chlorophenyl)-3-methylflavin and showed similar parasiticidal characteristics for the two new derivatives. The activities of five other erythrocytic enzymes tested were not impaired by the drugs, nor was the nucleotide metabolism of erythrocytes and/or parasites significantly changed. Permeation into red blood cells was demonstrated for one compound by 19F-NMR-spectroscopy. Inhibition of glutathione reductase might contribute to, or account for, the antimalarial activity of this group of flavin analogs.

Animals

Iron(III)hydroxamate transport of Escherichia coli K12: single amino acid replacements at potential ATP-binding sites inactivate the FhuC protein.

The mechanism of iron(III)hydroxamate transport appears to be of the periplasmic binding protein dependent transport (PBT) kind which is energized by ATP hydrolysis. The FhuC protein contains two domains typical of ATP-binding proteins. Lysine in domain I was replaced by glutamine and glutamate, and aspartate in domain II by asparagine and glutamate, resulting in FhuC derivatives which no longer transported ferrichrome and albomycin. FhuC inactivation by the aspartate-glutamate substitution is especially noteworthy since the negative charge thought to be involved in Mg2(+)-ATP binding remains the same and the two amino acid side chains differ in only a CH2 group. It is concluded that the two domains that represent consensus sequences among all peripheral cytoplasmic membrane proteins of PBT systems are involved in substrate transport.

ATP-Binding Cassette Transporters

Influence of some prostaglandins and prostaglandin analogues on PAF-induced shock in mice.

Prostaglandins and Prostaglandin-analogues were investigated for their ability to protect mice from platelet-activating factor (PAF) induced shock. 75% mortality in female NMRI mice was induced by i.v. injection of 75 micrograms/kg PAF. Nileprost and PGE1, the most potent substances, produced a dose dependent protection against PAF. Iloprost and PGI2 were less effective. PGE2, nalador, flunoprost and U 46619 were neither protective nor deleterious. The strong difference in the effectiveness between the two prostaglandins of the E-series and the poor effect of PGI2 and the PGI2 analogue is remarkable. Flunoprost and U 46619 that increased the TXB2 synthesis or release in two experimental models did not enhance the PAF mortality; TXA2 seems to be only a secondary mediator of the acute PAF-induced death.

Animals

Antimalarial activity of the ethanol/alcohol oxidase system in vitro.

Among other macrophage secretory products, H2O2 plays an important role in the host's defense against malaria (Wozencraft et al., Infect. Immun., 43, 664, (1984]. In our in vitro studies on the human malaria parasite Plasmodium falciparum, hydrogen peroxide was produced by the alcohol oxidase-catalyzed reaction ethanol + O2----acetaldehyde + H2O2 (EC 1.1.3.13). At concentrations of 8.7 mM (= 0.5%) ethanol and 0.1 U alcohol oxidase per ml culture, more than 95% of the parasites were irreversibly damaged. Acetaldehyde was found to be parasiticidal per se--probably by releasing immature forms of P. falciparum from erythrocytes--but CH3CHO concentrations as high as 90 mM were required for complete elimination of the parasites. Ethanol (less than 20 mM) or alcohol oxidase alone had no significant effect on parasite viability. As discussed, the ethanol/alcohol oxidase system might be of interest as a potential chemotherapeutic principle, especially since metabolism and pharmacology of the substrates and products are well understood.

Acetaldehyde

Influence of iloprost and various prostaglandin derivatives on mouse skin allograft survival, HLA-DR antigen expression and eicosanoid metabolism by human leukocytes.

Treatment of mice bearing allogeneic tail skin grafts with iloprost, a stabilized prostacyclin derivative, as well as dexamethasone prolonged graft survival. Nalador and flunoprost, stabilized prostaglandin E analogues, had similar but weaker effects. The thromboxane agonist U 46619 had no effect on graft rejection. An incubation of human monocytes with iloprost or prostaglandin E2 led to a dose-dependent reduction of HLA-DR antigen expression by these cells. Furthermore, a suppressive effect of these prostaglandin derivatives on the calcium ionophore stimulated release of arachidonic acid metabolites by human polymorphonuclear leukocytes has been shown, which demonstrates an antiinflammatory action of these drugs. Additionally, the eicosanoids were determined in the tail skin after complete allograft rejection. The importance of thromboxane for the rejection of skin grafts has not been confirmed. These data, along with the known antiaggregatory and antiischemic cytoprotective effects of iloprost, suggest that this newly developed drug may be all the more important in clinical organ transplantation.

Animals

Comparison of micronucleus frequencies and proliferation kinetics in three X-irradiated cell lines.

The kinetics of the occurrence of micronuclei was correlated with the survival of three mammalian cell lines of human, monkey, and mouse origin after irradiation with 240 kV X-rays. Particular attention was paid to the evaluation of the individual proliferation kinetics of the cell lines as well as to the characterization of micronuclei subpopulation with respect to size and possible biological importance using DNA and BUdR labelling techniques, fluorescence microscopy, and image analysis. The results demonstrate very characteristic size distributions of micronuclei for the three cell lines independent of radiation dose and time after irradiation. A close correlation between cell death and the occurrence of micronuclei (expressed as a calculated "MN index") after irradiation could be established only when the kinetics of progression of cells through the cell cycle (e.g. the doubling time) and the biological characteristics of micronuclei (e.g. BUdR positivity, the micronucleus frequencies, and the number of micronuclei per main nucleus) were taken into account. Therefore, the micronucleus assay might not be useful as a quantitative predictive assay in vivo but may allow qualitative estimations of radiation damage only because the necessary proliferation parameters of the cells might not be possible to establish in vivo.

Animals

[The acquisition of a certificate of expert knowledge for kitchen chefs from the viewpoint of the district hygiene inspectorate].

The paper demonstrates the experiences and problems of a hygiene inspectorate in the training and in-service training of kitchen staff in the field of hygiene. The efficiency of the training is to be improved by actively involving the students into the training in order to decrease the incidence of alimentation diseases in the GDR.

Communicable Disease Control

Systemic spread of Campylobacter jejuni after intravenous infections.

Mice were infected intravenously with Campylobacter jejuni in order to study systemic translocation of this vibrio, as well as the interactions between bacteria and the host's defense mechanisms. It was found that granulocytes phagocyte C. jejuni in the bloodstream and that phagocytosis could be stimulated with LPS-pretreatment or, less effectively, opsonizing antibodies. It could also be demonstrated that these circulating 'infected' granulocytes are eliminated from the bloodstream mostly by the hepatic Kupffer's cells and that virulent strains of C. jejuni persist in the liver up to thirty days. It has to be concluded that phagocytosis by granulocytes and clearance of C. jejuni from the bloodstream by the liver represent important defense mechanisms in systemic Campylobacter infections.

Animals

Influence of the PG-analogues iloprost, nalador and nileprost on rejection time and TXB2 content of murine tail skin allografts.

Iloprost (2 X 330 micrograms/kg sc./d) better than nalador (2 X 500 micrograms/kg sc./d) prolonged the average time until the complete rejection of murine tail skin allografts in inbred mice. Nileprost (2 X 500 micrograms/kg sc./d) showed a similar trend. The TXB2 content in the ambient skin at the transplantation site was significantly diminished by all three PG-analogues, but by nileprost more than by iloprost or nalador.

Animals

[Incidence of postoperative adhesions following use of various methods of coagulation. An animal experiment study].

In 5 groups of 20 rats each, equal areas of the uterus horns and of the corresponding peritoneum of the anterior abdominal wall were coagulated resp. vaporized. To achieve this endocoagulation, mono- and bipolar high frequency current, and CO2- and Neodym-YAG-lasers were used. After 2 resp. 4 weeks, no intraabdominal adhesions were found in two animals after endocoagulation and in one animal each after coagulation with bipolar high frequency current and with CO2-laser. The lowest adhesion rates were seen after endocoagulation and coagulation with bipolar high frequency current. After application of the YAG-laser, to the uterus horns adhesions were present in 100%, applying the YAG-laser to the anterior abdominal wall for a short time there were produced few adhesions. After coagulation resp. vaporization of equal areas of the anterior abdominal wall, significantly more adhesions were found after CO2-laser-application, compared to all other techniques (p less than 0.01). Adhesions to the abdominal wall were significantly less frequent than adhesions to the tubes (p less than 0.01) with all techniques except with the CO2-laser.

Abdominal Muscles

[The production of hybrid cells producing monoclonal antibodies against Toxoplasma gondii].

Hybridomas that secrete monoclonal antibody to Toxoplasma gondii have been developed. Two groups of 10 female BALB/c mice each were immunized either over a shorter (71 d) or longer (117 d) period at first with Toxoplasma lysate antigen and afterwards with intact tachyzoites of the RH strain. Higher titres of antibody were obtained with the long-period immunization. The fusion experiments have shown that both schemes of immunization approximately result in the same number (16 and 14% respectively) of hybridoma cell lines producing antigen-specific monoclonal antibodies. Hybridoma cultures secreting antitoxoplasma monoclonal antibodies were screened parallel by indirect immunofluorescence antibody test (IFAT) and enzyme immunoassay (EIA). 16 of the hybridoma cell cultures produced positive results only in the IFAT, 112 reacted only in the EIA and 21 were positive in both tests. The monoclonal antibodies 5B10, 5G6 and 1B2, which are positive in the IFAT form a chemical compound with the major antigens on the surface of RH tachyzoites. The patterns of fluorescence produced by these monoclonal antibodies are in conformity with those produced by using polyclonal sera of Toxoplasma gondii infected hosts (mouse, rabbit, man).

Animals