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Biomedical subjects

H Mohr

Publications and source records attributed to H Mohr.

At least 19 recordsLinked to original sources
PubMed1992

No evidence for neoantigens in human plasma after photochemical virus inactivation.

Photodynamic virus inactivation of human fresh plasma mediated by visible light in the presence of the phenothiazine dyes methylene blue or toluidine blue was investigated to determine whether it influences functional, structural, and immunological properties of plasma proteins. The activities of the coagulation factors I, VIII, IX, X, and XI were affected to a certain degree, while those of most other plasma proteins were not. The elution profiles obtained by ion exchange chromatography of untreated and photodynamically treated plasma were almost identical. Using a number of antisera against human plasma and single plasma proteins, different immunochemical techniques revealed identical patterns for untreated and treated plasma. Thus, there was no indication that the photodynamic virus inactivation procedure applied considerably influences the properties of plasma proteins.

Antigens↗
PubMed1992

Virus inactivated single-donor fresh plasma preparations.

Photodynamic virus inactivation of single units of human fresh plasma in their plastic containers can be achieved by illuminating the plasma with visible light in the presence of low concentrations of one of the phenothiazine dyes methylene blue or toluidine blue. This procedure abrogates the infectivity of numerous lipid-enveloped viruses including that of human immune deficiency virus-1. In contrast, the functional activities and immunological properties of plasma proteins are only moderately influenced. Animal studies and the first clinical data suggest that photodynamically virus inactivated fresh plasma is as well tolerated as conventional fresh frozen plasma.

Blood Banks↗
PubMed1991

The development of neutralizing antibodies in a patient receiving subcutaneous recombinant and natural interleukin-2.

Systemic administration of interleukin-2 (IL-2) in humans may induce antibodies specific to IL-2. The case is reported of a patient with metastatic rectal carcinoma who was treated with long-term subcutaneous IL-2 and a combination of subcutaneous IL-2 and interferon-alpha 2b (IFN-alpha 2b). This patient developed nonneutralizing and neutralizing anti-IL-2 antibodies recognizing both the recombinant and natural cytokine. Detectable serum levels of neutralizing antibodies were accompanied by the inhibition of immune responsiveness to systemic IL-2 in vivo.

Antibodies↗
PubMed1991

Modulation of natural and interleukin-2-induced tumour-cytolytic activities by the members of a protein family related to beta-thromboglobulin.

A preparation of three C-terminal fragments of the platelet protein beta-thromboglobulin was previously described to have immunomodulatory properties on phagocytic cells. One of the components is obviously identical to the recently described neutrophil-activating peptide 2 (NAP-2). In further investigations on this protein preparation (called factor C) we are able to show an additional influence on the tumour-cytolytic activities of mononuclear cells. Total neutralization of the factor C effect, by treating a factor C preparation with specific monoclonal antibody C24 prior to application in cell culture, proved that the effect is really restricted to factor C proteins. If factor C is given in combination with natural interleukin-2 (IL-2) a dose-dependent suppression of IL-2-mediated natural killer lymphokine-activated killer activity can be measured, which is first detectable 72 h after addition of factor C. Suppression does not occur if the both factors are added within a time interval of more than 12 h. Depletion of monocytes from mononuclear cells has no effect on factor-C-mediated cytotoxicity, demonstrating that factor C acts directly on lymphoid cells.

Amino Acid Sequence↗
PubMed1991

Photoinactivation of viruses in human fresh plasma by phenothiazine dyes in combination with visible light.

We developed a photodynamic method to inactivate viruses in human fresh plasma. Single plasma bags were illuminated with visible light in the presence of low doses of phenothiazine dyes like methylene blue or toluidine blue. By this treatment the infectivity of different enveloped viruses including the causative agent of AIDS, HIV-1, was completely removable from the plasma. Non enveloped viruses, however, proved to be more stable. The activities of clotting factors and other plasma proteins were only slightly decreased. There was no indication that the procedure led to important structural modifications of plasma proteins. The dyes are photodynamically active at concentrations much lower than those at which they are therapeutically used as antidots in the treatment of methemoglobinemia.

Cytopathogenic Effect, Viral↗
PubMed1991

A histomorphometric analysis of the effects of fluoride on experimental ectopic bone formation in the rat.

Ectopic bone formation was induced in 14 rats receiving 100 ppm fluoride in drinking water and in 14 control animals. Sections from ossicles removed after 14 and 20 days were sampled for stereological analysis. Bone volume density and bone volume were reduced in experimental animals on day 14 (p less than 0.05). This difference was no longer present after 20 days. On day 20, surface density and areas of formative surfaces were increased in the fluoride group (p less than 0.05). Osteoid seam thickness was higher in the fluoride group on both days (p less than 0.01). In conclusion, fluoride induced quantitative alterations in ectopic bone formation, and the presented model may prove a useful addendum to previous methods for investigation of fluoride effects on mineralization processes in vivo.

Animals↗
PubMed1991

Morphostereometry of heterotopic ossicles in the rat.

The objective of this study was to describe induced heterotopic bone formation in the rat using stereologic methods and to optimize the sampling for toxicologic studies. Bone formation was induced by implants of demineralized bone powder in 24 male Wistar rats. The ossicles formed were removed after 14, 16, 17, 18, and 20 days. From each ossicle, six sections were sampled equidistantly, and seven microscopic fields were analyzed in each section. Ossicle volume and weight decreased from Day 16 to Day 20. Bone volume density increased during the experimental period because of the reduction in ossicle volume, whereas the total bone volume did not change. Bone thickness increased from Day 14 to Day 20. No changes were observed in the surface density and total area of formative surfaces. The major part of the total variation was due to true variation between animals. The described histomorphometric methods may prove useful in quantitative toxicologic studies, e.g., of fluoride effects on cartilage and bone formation.

Analysis of Variance↗
PubMed1991

[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↗
PubMed1990

[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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗