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Biomedical subjects

H Lemke

Publications and source records attributed to H Lemke.

At least 55 records · Page 3Linked to original sources
PubMed1983

Long term toxicological studies on the progestin STS 557.

The toxicity of 17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one (STS 557) was studied by its oral administration of 0.1, 1.0 or 10.0 mg/kg/day to Wistar rats for six months, and of 0.01, 0.1 or 1.0 mg/kg/day to beagle dogs for six months, respectively. Levonorgestrel at a dose of 1.0 mg/kg/day was used as the standard in the dog study. With respect to the progestational activity of the compound the main target organs were the hypophysis, the reproductive organs and the adrenals. Mammary hyperplasia was observed in dogs treated with STS 557 or levonorgestrel at the dose of 1.0 mg/kg/day, but in no case mammary nodules could be detected. At the dose of 1.0 mg/kg/day STS 557 and levonorgestrel were found to increase the plasma insulin response to i.v. glucose in bitches, but neither the mean blood glucose levels nor the glucose utilization were affected. Moreover, during administration of both steroids to dogs temporary changes in serum concentrations of triglycerides and total cholesterol were noted. The results obtained in rats and dogs from functional and morphological investigations did not reveal any toxic side effects of STS 557 on the liver, the kidneys, the bone marrow or on blood coagulation. The effects on the reproductive organs observed following STS 557 especially in dogs are related to both the hormonal effects of the compound and the specific response of the dog to potent progestagens.

Animals↗
PubMed1982

Identification of Hodgkin and Sternberg-reed cells as a unique cell type derived from a newly-detected small-cell population.

In this study the antigenic profile of Hodgkin (H) and Sternberg-Reed (SR) cells from cases of Hodgkin's disease was analysed using a large panel of monoclonal and polyclonal antibodies reactive with cells of lymphoid and haemotopoietic origin. The aim of this investigation was, firstly, to throw light on the origin of H and SR cells and, secondly, to determine whether there is any evidence to support recent suggestions that H and SR cells differ antigenically between different histological categories of Hodgkin's disease. Frozen sections (from 24 cases) and paraffin sections (83 cases) were stained by immunoenzymatic methods and the results compared with those obtained from staining a wide variety of reactive and neoplastic tissue samples (including examples of tuberculosis, sarcoidosis, malignant histiocytosis, histiocytosis X, osteomyelosclerosis and non-Hodgkin's lymphoma). The results revealed that H and SR cells of all types of Hodgkin's disease consistently lack markers found on null cells, B cells, T cells, cells of monocyte/macrophage series, interdigitating reticulum cells, dendritic reticulum cells and erythropoietic and thrombopoietic cells. However, H and SR cells constantly expressed an antigen detectable with the recently produced monoclonal antibody Ki-I. The vast majority of typical and lacunar type H and SR cells contained the granulocyte-related antigens detected by monoclonal antibodies TU5, TU6, TU9 and 3C4, whereas other more or less specific granulopoietic cell markers (such as peroxidase, chloroacetate esterade, lysozyme, cationic leukocyte antigen and OKMI) were consistently absent. H and SR cells in cases of nodular paragranuloma (nodular type of Hodgkin's disease with lymphocyte predominance) were not monotypic in light chain type (as has been previously reported), but rather contained chi and lambda chains within the same cells, as do typical and lacunar type H and SR cells. Immunostaining of normal and hyperplastic lymphoid tissue with the Ki-I antibody led to the detection of a new, as yet unidentified, small-cell population of unknown origin and function, which is present between, around, and within cortical follicles. It is concluded from these findings that H and SR cells constitute a unique cell type that differs in many properties from all other known cell types. Furthermore, H and SR cells of the various histological types of Hodgkin's disease are more closely related than previously believed. It is suggested that the hitherto unknown cell population detected with the monoclonal antibody Ki-I in normal lymphoid tissue is the normal equivalent of H and SR cells.

Antibodies, Monoclonal↗
PubMed1982

Clustering of antigenic determinants on H-2 molecules.

The spatial relationship of individual antigenic determinants on H-2Kk and H-2Db molecules was investigated with seven different monoclonal anti-H-2Kk and seven anti-H-2Db antibodies. In these studies the binding of radiolabeled monoclonal anti-H-2 to target cells was competed by addition of various cold anti-H-2 antibodies. The results indicate that on both H-2Kk and H-2Db molecules the antigenic determinants are arranged in two spatially separated clusters. Thus, antibodies to determinants within a cluster show mutual inhibition of binding but do not block the binding of antibodies to the other cluster, and vice versa. Furthermore, in the case of H-2Db antigens it was observed that binding of antibodies to one cluster would considerably enhance the binding of antibodies to the other cluster. A preliminary Scatchard analysis indicated that the enhancing antibody did not alter the affinity of the radiolabeled antibody, but led to an increase of available binding sites on the cell membrane. In addition, binding inhibition studies revealed that the conventional private specificity H-2.2 of H-2Db consists of at least two independent sites on the molecule.

Animals↗
PubMed1981

Isolation of a cloned cell line expressing variant H-2Kk using fluorescence-activated cell sorting.

We describe here a method for the isolation of somatic cell variants that express a structurally altered gene product on their cell surface. The method makes it possible to select positively for cells of the variant phenotype which is defined by loss of a given antigenic determinant. As an example, we present the isolation of a cloned cell line expressing a structurally altered H-2Kk molecule, designated H-2KkS1. Cells of this phenotype were found to be present in the wild-type population at a frequency of 10(-5)-10(-6) and were isolated in three rounds of selection in the fluorescence-activated cell sorter (FACS) and subsequent growth in vitro.

Animals↗
PubMed1979

Studies on the quantification of local tissue injury following intramuscular injection of aqueous solutions. VIII. The local lesion after application of turimycin in different preparations.

The increase in drug concentration in aqueous solutions is not responded to by a comparable enlargement of volume of necrosis after intramuscular injection. After application of TURIMYCIN the lesion is more voluminous than those caused by penicillin, lower than those following OTESOLUT and nearly equal to those caused by 5% WOFAPYRIN (phenylbutazone + aminophenazone 1:1).

Animals↗
PubMed1977

The role of fetal calf serum in the primary immune response in vitro.

The mode of action of 2-mercaptoethanol (2-ME) on the primary immune response in vitro was investigated. Fetal calf serum (FCS) was preincubated with 2-ME and lyophilized to remove free 2-ME. This 2-ME-treated FCS was able to substitute the function of adherent cells in the primary immune response against sheep red blood cells (SRBC) in vitro; Fractionation of 2-tme-treated FCS on a Sephadex G-100 column showed that 2-ME acted on a high molecular serum component which after activation, could substitute for macrophages. In order to obtain a humoral immune response against SRBC in vitro, spleen cells require selected FCS. These "good" sera could be distinguished from "deficient" sera by their higher content of this 2-ME-activated factor. The height of the in vitro immune response to SRBC was dependent on the amount of activated factor added to the culture medium. FCS normally required in the culture medium could be completely replaced by the factor-containing fraction without deleterious effect on the culture medium. The factor should be added to the spleen cells during the first 24 h of culture and remain there for 72 h in order to obtain an optimal immune response. The factor could be partially absorbed by spleen cells but not by SRBC. The relationship between macrophage, 2-ME, and FCS in eliciting an in vitro primary immune response is discussed.

Antibody Formation↗
PubMed1977

Growth regulation of a murine lymphoma cell line by a 2-mercaptoethanol or macrophage-activated serum factor.

A mouse lymphoma cell line has been established that is dependent for growth on the presence of an activated serum component. This growth factor is found in an inactive form in fetal bovine serum (FBS) and can be activated by 2-mercaptoethanol and by macrophages. A factor-containing fraction can be separated from FBS by Sephadex G-100 chromatography and once activated, can be used as a substitute for whole serum in the culture medium without adverse effect on the cell growth. The significance of these findings with respect to the study of the immune response and cancer research is discussed.

Animals↗
PubMed1977

Humoral primary immune response in vitro in a homologous mouse system: replacement of fetal calf serum by a 2-mercaptoethanol or macrophage-activated fraction of mouse serum.

The primary immune response in mouse spleen cell cultures against heterologous red cell antigens is dependent on the medium being supplemented with selected batches of fetal calf serum. Mouse serum itself is not able to support this response. The active immune response-supporting component in fetal calf serum seems to be a distinct factor (s), which has been partially purified by Sephadex G-100 filtration and termed MaSF-2-mercaptoethanol-activated serum factor. In this report it is demonstrated that MaSF is also present in mouse serum. For functional detection, mouse MaSF has to be separated from higher m.w. inhibitors, and has to be activated by 2-ME. After separation and activation mouse MaSF can support the primary immune response in a completely homologous in vitro culture system. Evidence is presented that MaSF can also be activated by macrophages. It is concluded that macrophages and 2-ME have the same mode of action in the primary immune response in vitro, i.e., induction of lymphocyte competence by activation of a serum factor.

Animals↗
PubMed1976

Polyclonal stimulation of lymphocytes by macrophages.

To analyze the interaction between macrophages and splenic lymphocytes with reference to time and concentration, the Mishell-Dutton system was divided into two experimental steps. Step 1 consisted of the cocultivation of spleen cells with various doses of macrophages for different periods of time, while in step 2 macrophages were removed, spleen cells transferred to fresh petri dishes and cultivated until plaque assay. Cocultivation of spleen cells with high doses of macrophages for 4--8 h markedly enhanced the DNA synthesis and plaque-forming cell (PFC) response of sheep red blood cell-stimulated and unstimulated cultures. A cocultivation longer than 24 h resulted in an inhibition of both DNA synthesis and PFC response of spleen cells. These studies suggest a nonspecific function of macrophages on proliferation and differentiation processes in antibody formation.

Animals↗
PubMed1976

The role of adherent cells in the immune response. Fibroblasts and products released by fibroblasts and peritoneal cells can substitute for adherent cells.

The primary immune response to sheep erythrocytes in adherent cell-depleted cultures was restored by adding a critical number of peritoneal cells. Complete substitution was achieved also with supernatants from allogeneic and syngeneic peritoneal cells. Both living fibroblasts and supernatants from fibroblast cultures were found to be highly efficient substitutes for adherent cells in both syngeneic and allogeneic systems. Supernatants from non-antigen-reated peritoneal cells and fibroblasts caused increased DNA synthesis and induction of polyclonal antibody synthesis in normal spleen cells. Thus, adherent cells need not function in the immune response by presenting antigen to the B cells via 'IgT' or by releasing signal-2 activity, which acts on lymphocytes that have already received signal 1.

Animals↗
PubMed1976

Function of 2-mercaptoethanol as a macrophage substitute in the primary immune response in vitro.

The mechanism by which 2-ME acts as a macrophage-substitute for the induction of a primary PFC response to SRC in vitro was studied in macrophage-depleted mouse spleen cell cultures. 2-ME could replace macrophages only in FCS-supplemented cultures. Evidence is presented that the function of 2-ME is independent of residual macrophages. Neither normal nor macrophage-depleted spleen cell cultures from congenitally athymic nude mice supplemented with 2-ME, with or without FCS, could give rise to a primary in vitro anti-SRC immune response. 2-ME, at an optimal concentration of 10(-5) M, induced DNA synthesis in normal and macrophage-depleted spleen cells in both FCS-containing and serum-free cultures. The peak response occurred on day 3. The stimulation was accompanied by a polyclonal B cell activation to antibody secretion which was much more pronounced in FCS-containing than in serum-free cultures. Spleen cells from nude mice showed a weaker DNA stimulation than did cells from normal mice in FCS-containing cultures, and nearly no response under serum-free conditions. T cells obtained by a nylon column adherence method from normal mouse spleen cells showed good DNA synthetic responses in FCS-containing, but no response in serum-free cultures. These results show that 2-ME has weak mitogenic activity for B cells, and in combination with FCS, strong mitogenic activity for T cells. Since the macrophage provides stimulation to the T cell in the primary anti-SRC PFC response in vitro, these results suggest that the direct mitogenic activity of 2-ME with FCS on T cells provides the functional substitution for macrophages.

Animals↗