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Biomedical subjects

H Mohr

Publications and source records attributed to H Mohr.

At least 55 records · Page 3Linked to original sources

[Virus inactivation of plasma].

A procedure for the virus inactivation of single donor plasma is described. Virus inactivation is achieved by the combination of 1 mumol of phenothiazin dye, e.g. methylene blue and toluidine blue, and visible light. Using this method VSV, HSV and HIV, as well as other viruses, were inactivated. It could be shown that virus inactivation caused only a minimal reduction in the biological activities of coagulation factors and inhibitors. Furthermore, there was no indication for either neo-antigens or IgE-antibodies. In tolerance studies on dogs it was demonstrated that virus-inactivated autologous plasma caused no toxic effects.

Animals↗

[Fluoride effect on bone formation--an overview].

The purpose of this review is to evaluate our present knowledge of fluoride effect on bone formation on basis of the literature. It is likely that fluoride affects the remodelling processes of the skeleton as well as growth related bone formation. During bone remodelling the amount of bone and osteoid tissue is increased by alteration of the balance between resorption and formation. This finding may be accompagnied by impaired mineralization. In studies of fluoride effect on growth related bone formation a number of quantitative histologic alterations have been observed. These include reduction in epiphyseal plate thickness and changes in cellular morphology as well as a retardation of mineralization. The pathogenetic mechanisms behind the observed effects and the variation in tissue response are still unexplained. Fluoride may have a direct cellular effect causing disturbances in cell morphology and metabolism, but the effects may also involve local supracellular mechanisms as well as the general homeostasis of the individual.

Bone Development↗

Low-dose subcutaneous recombinant interleukin-2 in advanced human malignancy: a phase II outpatient study.

Recombinant interleukin-2 (rIL-2; EuroCetus, Amsterdam, Netherlands) was studied in an outpatient phase II trial in 14 patients with progressive metastatic renal carcinoma, malignant melanoma, and colorectal cancer. Escalating doses of rIL-2 were administered as subcutaneous bolus every 12 hours, starting at 0.3 million U/m2/d. A 100% dose increase occurred at weekly intervals, up to a maximum of 2.4 million U/m2/d. Responding patients or patients with stable disease after 4 weeks of rIL-2 (n = 9) were continued on maintenance therapy at 1.8 million U/m2 of rIL-2 administered once weekly. After 12 weeks of therapy, one renal cell cancer patient had a partial regression in lung metastases. Bolus injection of rIL-2 (1.2 million U/m2) resulted in peak serum levels of 25 to 30 U/ml. Toxicity of this regimen was moderate, with local inflammation at the injection sites, grade I-II (World Health Organization) malaise, nausea and/or vomiting, and fevers in 70% to 100% of patients treated. Thyroid dysfunction was observed in 10 patients receiving subcutaneous rIL-2; four of these patients had laboratory evidence of hyperthyroidism, and one had hypothyroidism. rIL-2-induced toxicity reversed spontaneously after cessation of treatment. In all patients receiving rIL-2, a dose-dependent increase in peripheral blood lymphocyte and eosinophil counts was noted, with a mean of 2.6 and 3.8 x 1,000/microliters after 4 weeks of therapy; mean lymphocyte and eosinophil counts were measured at 2.0 and 2.4 x 1,000/microliters in patients who received prior high-dose chemotherapy, compared with 3.2 and 5.1 x 1,000/microliters in those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Anorexia↗

A fluorescence-based assay for quantitation of lymphokine-activated killer cell activity.

A fluorescence assay for the quantitation of tumor cell lysis by activated and non-activated killer (LAK) cells is described. The target cells are labelled with a europium chelate (Eu-diethylenetriaminopentaacetate) and after cytolysis caused by the LAK cells the Eu3+ complex is released into the culture supernatant. The addition of beta-naphthoyltrifluoroacetone to culture supernatant aliquots leads to the formation of a highly fluorescent chelate which can be measured with a time-resolved fluorometer. The influence of various assay parameters has been evaluated including incubation time, effector-to-target cell ratio, the target cell line and different concentrations of interleukin-2 during cell culture. The optimized time-resolved fluorometric assay was found to be as simple and sensitive as the commonly used cytotoxicity assay in which the release of 51Cr from the labelled target cells is measured. In addition the assay is much faster and safer since the label is not radioactive.

Cell Communication↗

HIV-2 antibody testing of blood donors with doubtful immunoblot results for HIV-1.

Antibodies against human immunodeficiency virus type-1 (HIV-1) in samples from blood donors are commonly detected by various enzyme-linked immunosorbent assays (ELISA) and by confirmatory tests, e.g., "Western blot" or immunofluorescence tests. Immunoblot reactivity, which is directed only towards the HIV-1 core proteins p 18, p 24 and p 55, may represent false-positive reactions. Out of 125,000 blood donations, 140 were repeatably HIV-1 antibody reactive by ELISA; of these, 20 were doubtful positive sera with isolated p 18 and/or p 24 bands in the HIV-1 confirmatory assay. Antibodies to HIV-2 are known to cross-react with these HIV-1 core proteins. We therefore assayed the 20 sera by immunofluorescence and immunoblotting for the presence of antibodies to HIV-2. None of these doubtful HIV-1 antibody positive blood donor sera was found to have antibodies to HIV-2.

Blood Donors↗

Cytokines and pancreatic cancer. The effect of rIFN-gamma, HuLeIFN, rTNF-alpha, and LAK-cells on pancreatic and other gastrointestinal tumors in vitro.

A panel of 10 digestive tract carcinoma cell lines (6 pancreatic carcinomas) was assayed for their sensitivity to HuLeIFN, human rIFN-gamma, rTNF-alpha and allogeneic human LAK-cells in vitro. In addition, a combination of rIFN-gamma + rTNF-alpha was tested on 3 pancreatic carcinoma cell lines. Whereas 6/7 cell lines were completely resistant to HuLeIFN, rIFN-gamma and rTNF-alpha did inhibit growth of some carcinomas tested. The individual sensitivity was heterogenous as is already known from cytostatics. Response to rIFN-gamma tended to increase with increment of cell doubling time. Only high concentrations (greater than 1000 U/ml) of rIFN-gamma displayed cytotoxicity on sensitive tumors. The antitumoral effect of rIFN-gamma was stimulated by rTNF-alpha. As revealed by isobole analysis this interaction was synergistic in all pancreatic carcinomas tested. In comparison to rIFN-gamma or rTNF-alpha the response to LAK-cells was slightly superior at high effector target ratios, even though heterogenous.

Biological Factors↗

Posttranslational modification of interleukin-2 is a late event during activation of human T lymphocytes by ionophore A23187 and phorbol ester.

Human peripheral blood lymphocytes secrete high titers of interleukin-2 (IL-2) after stimulation by Ca2+-ionophore A23187/phorbol 12-myristate-13-acetate. During the first 30 hours of incubation cells secrete only the nonglycosylated IL-2 M form of the lymphokine, the glycosylated forms IL-2 N1,2 being detected only after prolonged culture times (30-48 h). After recultivation of cells for a second 48 h period (without additional mitogen), the glycosylated and nonglycosylated IL-2 forms are secreted at a constant ratio of 7:3 throughout. The detection of glycosylated IL-2 is parallelled by an increase in cellular glycosyltransferase activities involved in formation of sialylated oligosaccharides O-linked to proteins.

Calcimycin↗

Treatment with natural human interferon alpha of a CML-patient with antibodies to recombinant interferon alpha-2b.

A patient with Philadelphia-chromosome positive chronic myelogenous leukemia developed interferon antibodies on treatment with recombinant interferon alpha-2b. Clinically this event corresponded with progressive disease. No cross-reactivity of antibodies with human leukocyte interferon was found by Western blot. Treatment was switched to human leukocyte interferon with an obvious clinical effect: WBC was reduced and platelet count stabilized, but the effect was transient and no hematologic remission was achieved. Human leukocyte interferon may be an alternative in CML-patients with neutralizing antibodies to recombinant interferon alpha.

Antibody Formation↗

Co-induction of lymphokine synthesis by the antineoplastic bryostatins.

The macrocyclic lactone bryostatins, isolated from marine bryozoans, have been found to be strong inhibitors of e.g., the P 388 murine lymphocyte leukemia cell line and in vivo systems. Presently, bryostatin 1 is under preclinical development as a potential anticancer drug, although the bryostatins exhibit some of the same biological effects as the tumor promoting phorbol-12-myristate-13-acetate (PMA), especially activation of protein kinase C in certain cell types. In our experiments, we investigated the influence of bryostatin 1 on the synthesis of interleukin 2 (IL2) and interferon-gamma (IFN-gamma) by ionophore A23187 or mitogen-induced human blood lymphocytes. These results were then compared with those achieved using the two tumor promotors PMA and teleocidin. Our data indicate that bryostatin 1 is comparable to these two other drugs in increasing production of the two lymphokines 10-100-fold. The IL2 and IFN-gamma production kinetics of cultures induced with either A23187/bryostatin 1 or A23187/PMA were practically identical. The general pattern of peptides, however, released from bryostatin 1 coinduced cultures differed from that obtained when PMA was used.

Antineoplastic Agents↗

[Effect of new imaging procedures on conventional roentgen diagnostic methods].

The diagnostic radiology workload of a general hospital served as basis to assess the statistical distribution of various diagnostic radiology methods and the inroads made by new imaging methods on the conventional ones: CT, DAS, sonography and endoscopy. In particular, the statistical breakdown shows how these methods have been applied in examining the gastrointestinal tract, the kidneys, the gallbladder and biliary tract, and how they have influenced the frequency rate of special examination methods such as angiography and myelography. Statistic assessment of the results obtained during the past ten years shows an increasing predominance of less invasive examination methods and increasing use of endoscopic methods for examining the gastrointestinal tract, the sum total of examinations remaining approximately the same throughout.

Angiography↗