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Biomedical subjects

M Dietrich

Publications and source records attributed to M Dietrich.

At least 145 records · Page 8Linked to original sources

Thromboxane production by perturbed bovine aortic endothelial cells in culture.

Bovine aortic endothelial cells in culture were incubated with endotoxin. The amount of thromboxane A2 synthesized was then determined by a specific radioimmunoassay for thromboxane B2. After a lag of several hours the cells changed their shape and parallel to the change in cell shape release of thromboxane B2 occurred. At 24 h the amount of thromboxane B2 generated in response to endotoxin was 200-fold above baseline. Thromboxane B2 generation could be blocked by aspirin and the specific thromboxane synthetase inhibitor UK 37248. The endotoxin effect was dependent on protein and RNA synthesis as evidenced by the inhibitory action of cycloheximide (1.5 microM) and actinomycin D (2 micron).

Animals↗

Haemostatic alterations in malaria correlate to parasitaemia.

Fibrin(ogen) degradation products, platelet counts, antithrombin III, and the components of the Factor VIII complex were studied in a total of 80 patients with Plasmodium falciparum, Plasmodium vivax or Plasmodium ovale infections. The haemostatic findings were correlated to the numbers of parasitized erythrocytes and to each other. The results indicate that haemostatic changes in malaria correlate with the degree of parasitaemia. Evidence for moderate hyperfibrinolysis was found in patients with high P. falciparum parasitaemias only. Thrombocytopenia closely corresponded to parasitaemia and to von Willebrand factor levels, but appeared not to be linked to a consumption of coagulation factors. It was concluded that thrombocytopenia in malaria is not indicative of disseminated intravascular coagulation (DIC) but may relate to endothelial damage.

Erythrocytes↗

[NMR studies of the central nervous system in pediatrics].

The central nervous system in 70 infants, children and adolescents has been examined by NMR. Phase I of the continuing investigation dealt with the applicability and scope in this group of patients. A retrospective comparison with CT was used to examine the possibility of enhancing and differentiating various tissues. The results have shown that NMR can extend the diagnostic possibilities beyond those of CT in the paediatric age group.

Adolescent↗

Differences in humoral immunogenicity between herpes simplex virus types 1 and 2.

Infection of NMRI mice with increasing doses of six different strains of herpes simplex virus type 1 (HSV-1) induced increasing levels of neutralizing antibodies. In contrast, three strains of HSV-2, irrespective of the dose, induced only marginal antibody responses. Only strain HG 52 (HSV-2) at high doses of infection stimulated antibody formation. The virus content of some organs in 6- to 8-week-old mice appeared to be lower after HSV-2 than after HSV-1 infection. Application of immune-modulating drugs [silica or poly(I) X poly(C) coupled via L-lysine to CM-cellulose] resulted in little augmentation of antibody formation if compared to HSV-1 infection. Secondary infections with HSV-1 or HSV-2 after a primary dose of HSV-1 were followed by a marked booster response. In contrast, a primary infection with HSV-2 suppressed secondary responses of HSV-1 and HSV-2, thus indicating fundamental differences between the antibody-stimulating potency of HSV-1 and HSV-2 strains.

Animals↗

Modulation of cytotoxicity of menadione sodium bisulfite versus leukemia L1210 by the acid-soluble thiol pool.

We investigated the mechanism of antitumor activity of the water-soluble derivative of menadione, menadione sodium bisulfite (vitamin K3), versus murine leukemia L1210. Vitamin K3, in concentrations greater than 27 microM, caused time- and concentration-dependent depletion of the acid-soluble thiol (GSH) pool. Maximal GSH depletion to 15% of control occurred at 45 microM vitamin K3. Vitamin K3-mediated GSH depletion and vitamin K3-mediated growth inhibition were abrogated by coincubation with 1 mM cysteine or 1 mM reduced glutathione but not by 1 mM ascorbic acid or 180 microM alpha-tocopherol. Low concentrations of vitamin K3 (9-27 microM) elevated both the GSH pool and the total glutathione pool, the latter to a greater degree. Vitamin K3 also caused an increased rate of superoxide anion generation by L1210, maximal at 45 microM vitamin K3 (300% of control), and a concentration-dependent depletion of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) and total nicotinamide adenine dinucleotide phosphate (NADP) pools. Forty-fifty % depletion of the NADPH pool occurred after exposure to 27 microM vitamin K3 and 100% occurred at 36 microM vitamin K3; 27 microM vitamin K3 is a nontoxic concentration of vitamin K3. Loss of NADPH and total NADP was prevented by coincubation with 1 mM cysteine but not by coincubation with ascorbic acid or alpha-tocopherol. We conclude that tumor cell growth inhibition by vitamin K3 is modulated by acid-soluble thiols and may be caused by GSH pool and/or NADPH depletion. Toleration of partial NADPH depletion by L1210 cells may indicate that a threshold level of NADPH loss of greater than 50% is necessary for toxicity. NADPH depletion may be a toxic effect common to quinone drugs. Equitoxic concentrations of vitamin K3, phylloquinone, lapachol, dichlorolapachol, and doxorubicin caused L1210 NADPH pools to deplete to 30 +/- 10 (SD), 60 +/- 10, 60 +/- 11, and 80 +/- 12% of control, respectively. In contrast, GSH depletion may not be a common mechanism of toxicity. Of these quinones, only vitamin K3 caused significant GSH depletion when studied in equitoxic concentrations.

Animals↗

Precipitable immune complexes in healthy homosexual men, acquired immune deficiency syndrome and the related lymphadenopathy syndrome.

Increased levels of 3% PEG precipitable circulating immune complexes (CIC) were found in healthy homosexual men, in homosexual patients with the acquired immune deficiency syndrome (AIDS), and in the AIDS related lymphadenopathy syndrome (LAS). The degree of CIC elevation increases from healthy homosexual men to LAS and AIDS. Patients suffering from AIDS associated with opportunistic infections had a more pronounced increase in CIC than patients with AIDS associated Kaposi's sarcoma. In LAS and AIDS the amount of CIC correlated with the degree of inversion of the T4/T8 lymphocyte ratio, whereas in healthy homosexual men with increased levels of CIC the T4/T8 ratio was not significantly altered. Laser nephelometric partial components analysis revealed that these complexes were of a complement poor subtype with low component levels of C4, C1q and C3c. IgM and IgG were found to be the major components. It is suggested that these CIC might represent a marker of the total antigenic burden of the immune system. Possibly, they are of prognostic and monitoring value for clinical handling of patients at risk for AIDS.

Acquired Immunodeficiency Syndrome↗

[Mebendazole treatment of echinococcosis].

Forty patients with echinococcosis were treated with mebendazole (approximately 50 mg/kg body weight) and under observation for up to 8 years. In 8 patients, E. multilocularis-infection was diagnosed whereas 32 patients had liver (n = 19 lung, n = 7) or other infestations of E. granulosus. 23 patients had been treated with mebendazole alone. 20 further patients received the treatment pre- and post-operatively and in the remaining cases mebendazole was given pre- or post-operatively according to the patients' requirements. Besides the clinical and laboratory findings, morphological parameters of organ infestation due to the parasites were examined repeatedly by x-ray, ultra sound, Ct-scan or scintigram. In the course of treatment we noticed that mebendazole had a certain effect in the case of E. multilocularis-infection and in the case of lung infestation due to E. granulosus. Furthermore, patients who were treated with mebendazole and who were under observation for several years, showed improvement of the liver cyst. The analysis of all morphological data available from patients with liver cysts indicated that marked changes had already been observed in the period of one to thirty months after the beginning of therapy.

Echinococcosis↗

[T and B cell reactions in AIDS and AIDS risk groups].

In addition to T-cell defects AIDS shows a separate B-cell dysfunction. Elevated spontaneous IgG-levels (not IgM) and a lacking proliferative and differentiation response to polyclonal B-cell activators can be demonstrated in vitro.

Acquired Immunodeficiency Syndrome↗

Vitamin K3 inhibition of malignant murine cell growth and human tumor colony formation.

To assess the antineoplastic potential of vitamin K compounds, the effects of vitamin K3 (menadione), vitamin K1 (phylloquinone), and warfarin on L1210 murine leukemia cell growth were studied in a flask culture system. When the cytotoxic potential of vitamin K3 was recognized, the effects of vitamin K3 on human tumor colony formation were studied in 34 tumor explants using a soft agar (clonogenic) assay system. Complete inhibition of L1210 growth in flask culture was achieved at concentrations of 200 micrograms/ml of warfarin, 75 micrograms/ml of vitamin K1, and 4 micrograms/ml of vitamin K3. Combined use of vitamin K and warfarin enhanced cytotoxicity because a concentration of 1 micrograms/ml of vitamin K3 together with 70 micrograms/ml of warfarin resulted in nearly complete inhibition of L1210 growth. Comparable inhibition of growth was seen against malignant murine cell lines in the soft agar assay system, where greater than 70% decrease in colony formation was seen with vitamin K3 at concentrations of 6.4 micrograms/ml for L1210 leukemia and 1 microgram/ml for HII4E hepatoma lines. Vitamin K3 was also cytotoxic in the same dosage range when tested in vitro against the 34 human tumor explants in the soft agar assay system. Tumor types evaluated included adenocarcinoma of the breast (16 patients), ovary (five), colon (two), stomach (two), kidney (two), and unknown primary (two); squamous cell carcinoma of the lung (two); melanoma (one), transitional cell carcinoma of the bladder (one); and hepatocellular carcinoma (one).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antibodies to ATLV/HTLV-1 in Africa.

Almost 4000 sera from seven African states were examined for antibodies to ATLV/HTLV-1. Between 1% and 8% of healthy people from sub-Saharan Africa have such antibodies. The highest frequency was observed in Gabon. There were considerable variations between villages. The percentage of seropositives and the mean titre increased with age. Our findings suggest that the African continent is the largest endemic area for ATLV.

Adolescent↗

Raised serum neopterin levels and imbalances of T-lymphocyte subsets in viral diseases, acquired immune deficiency and related lymphadenopathy syndromes.

D-erythro-neopterin, a biochemical marker of cell-mediated immune response, was found to be significantly (p less than 0.001) elevated in the serum of homosexual patients with acquired immunodeficiency syndrome and related lymphadenopathy syndrome. The most pronounced rise was observed in viral diseases causing a numerically measurable activation of the immune system such as EBV or CMV infections. In the latter patient groups, the increase in T8+, HLA-DR+ and monocytic antigen+ lymphocyte subsets correlated with the raised neopterin level. Thus, neopterin seems to be released under various conditions in viral diseases and may reflect a functional state of T-lymphocytes irrespective of the actual number expressing differentiation antigens on the cell surface.

Acquired Immunodeficiency Syndrome↗

Plasmodium falciparum-malaria: resistance to chloroquine, but sensitivity to mefloquine in the Gabon. A prospective in-vitro study.

A determination of the sensitivity to chloroquine and to mefloquine was carried out in malaria patients of the Albert Schweitzer Hospital, Lambarene, Gabon, by using the schizont maturation test. The chloroquine testing showed in 6 of 31 cases a schizont maturation at 1.14 pmol/microliter of blood and more; this means an in-vitro resistance in 19% of the cases. The evaluation of the effective concentrations (i.e. concentrations producing the appropriate inhibition of schizont maturation) with the probit analysis yielded for chloroquine an EC50 of 0.2537 X 10(-6) mol/l of blood and an EC90 of 0.8317 X 10(-6) mol/l of blood. In the testing of mefloquine, schizont maturation was found in 3 of 31 cases in concentrations of 1.6 pmol/microliter of blood, the probit analysis, however, showed effective doses in the normal range with an EC50 of 0.2192 X 10(-6) mol/l of blood and an EC90 of 0.7863 X 10(-6) mol/l of blood. These results demonstrate the alarming observation of Plasmodium falciparum strains resistant in-vitro to chloroquine in a region where in vivo resistance has not been observed hitherto.

Adolescent↗

[Malaria].

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Antimalarials↗

[Bilharziasis].

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Antiplatyhelmintic Agents↗