PubMed Health⌕ Search

Biomedical subjects

M Timm

Publications and source records attributed to M Timm.

At least 37 records · Page 2Linked to original sources
PubMed1995

Prevalence of the fimbrial antigens F18 and K88 and of enterotoxins and verotoxins among Escherichia coli isolated from weaned pigs.

Until recently, the fimbrial F18 antigen has been provisionally designated F107, 2134P, or 8813. Using the slide agglutination test, this antigen was shown to be present on 139 of 160 Escherichia coli strains of type O139:K82 and on all of the 146 K88-negative strains of the other pathogenic porcine serotypes. These strains were isolated from weaned pigs which in most cases had died from postweaning colibacillosis. All strains were haemolytic. With only three exceptions, they produced verotoxin and/or enterotoxin. The F18ab variant strongly predominated on the O139:K82 strains and was found on about half of the O138:K81 strains and a few O157 strains, whereas the other strains carried the F18ac variant. In serotypes which can carry either F18 or K88 fimbriae, closer clonal relationships between the strains associated with F18 and those associated with K88 were missing.

Animals↗
PubMed1995

Regional variations in ETA/ETB binding sites in human coronary vasculature.

Endothelin (ET)-1 is an endothelium-derived constrictor peptide that is believed to play a pathophysiologic role in coronary artery disease. Receptors for this peptide have been identified on human coronary tissue by in vitro autoradiography. A number of available compounds are selective for ETA or ETB receptors. Here we have used radiolabeled PD 151242 and BQ 3020 to identify ETA and ETB binding sites on sections of human coronary vasculature. ETA receptors are associated with smooth muscle of the coronary artery. Smooth muscle ETB receptor binding is weak at proximal portions of this vessel but increases toward distal regions. ETB receptors are exclusively associated with myocardial capillaries. Our results indicate that, apart from ETA-induced vasoconstriction, stimulation of ETB receptors at distal regions of the coronary vasculature and myocardial microvessels may play an important role in the pathophysiology of coronary syndromes.

Autoradiography↗
PubMed1995

[3H]bosentan binding to human coronary artery: functional correlates.

The binding characteristics and localization of bosentan, an orally active endothelin-1 (ET-1) antagonist, were studied on sections of human coronary artery by in vitro autoradiography. Competition studies were performed to determine the ability of bosentan to prevent [125I]ET-1 binding to the coronary vasculature. The effects of bosentan on ET-1-induced contraction of the coronary artery were also studied in vitro. [3H]Bosentan bound to the tunica media of the human coronary artery. Unlabeled bosentan prevented [125I]ET-1 binding to this vessel in a concentration-dependent manner, and functional studies indicated that bosentan antagonizes ET-1--induced constriction. These data show that bosentan is able to reduce ET-1 binding to the human coronary artery and ET-1 constrictor effects in vitro. Bosentan is an orally active ET-1 antagonist, and these results suggest that this compound might be used to block the effects of locally released ET-1 in pathologic conditions, such as atherosclerosis, angina, and myocardial ischemia.

Autoradiography↗
PubMed1995

Endothelin-like immunoreactivity in atherosclerotic human coronary arteries.

Endothelin-1 (ET-1) is an endothelium-derived peptide with powerful vasoconstrictor and mitogenic properties. A pathophysiologic role for ET-1 has been suggested, because increased plasma and tissue levels of this peptide have been described in a number of disease states, including atherosclerosis. Immunocytochemistry was carried out on sections of coronary arteries from patients undergoing cardiac transplantation to identify regions exhibiting ET-1-like immunoreactivity (ET-LI). ET-LI was associated with endothelial cells of the lumen and with microvascular endothelial cells of the adventitia, regions of neovascularization, and recanalization within atherosclerotic plaques. ET-LI was observed in the tunica media, and patches of immunostaining were also associated with smooth-muscle cells within the plaque. These results indicate that ET-1 not only is released from the vascular endothelium but, under certain conditions, is also generated by smooth muscle cells. An autocrine action of ET-1 is well established, and our results suggest that this peptide is involved in neovascularization and smooth-muscle cell proliferation associated with atherosclerosis.

Coronary Artery Disease↗
PubMed1994

bcr/abl expression in 32D cl3(G) cells inhibits apoptosis induced by protein tyrosine kinase inhibitors.

Eight protein tyrosine kinase inhibitors with in vitro epidermal growth factor receptor kinase 50% inhibitory concentration values ranging from 0.043 to 22 microM were studied for their ability to inhibit the growth of the murine interleukin-3 (IL-3) dependent myeloid 32D cl3(G) cell line and, a subclone (LG7) transformed to IL-3 independent growth by retroviral transduction and expression of the chronic myelogenous leukemia-associated protein tyrosine kinase p210bcr/abl. Cell proliferation 50% inhibitory concentration values ranged from 4 to 250 microM, and one compound was not inhibitory at 500 microM. The dose-cell proliferation curves were remarkably similar for parental 32D cl3(G) cells + IL-3 and LG7 +/- IL-3, and reversion of LG7 cells to IL-3 dependence was not observed, suggesting that none of the compounds tested could selectively inhibit p210bcr/abl. However, 6 compounds induced the appearance of a 200-base pair nucleosomal DNA ladder characteristic of apoptosis at 24 h in parental 32D cl3(G) cells + IL-3, which mimicked the effects of IL-3 withdrawal alone, but not in similarly growth arrested LG7 cells that eventually developed a necrotic pattern of DNA fragmentation. These studies suggest that the expression of p210bcr/abl can suppress apoptotic signal transduction and that this may contribute to the development of the myeloid hyperplasia that occurs in chronic phase chronic myelogenous leukemia.

Animals↗
PubMed1994

[Content of trans-fatty acids in food].

The fatty acid composition of the fat in 197 food samples has been analyzed by gas liquid chromatography. The use of a 30 m capillary column coated with CPSil88 permitted the separation of the cis and trans isomers. The trans fatty acid content of milk and milk products ranged from 1.9 to 7.9%. Meat samples from ruminants contained 2.0-10.6% trans fatty acids. In pork fat the amounts were less than 0.5%. Sausages and other meat products contained high levels of pork fat. Therefore these samples contained less than 1% trans fatty acids, with the exception of some pure beef products. The amounts of trans fatty acids in foods which may contain hydrogenated oils ranged from 0 to 34.9%. In food samples with high levels of trans fatty acids lower contents of saturated fatty acids were analyzed.

Animals↗
PubMed1992

Clonal evolution in a myeloid cell line transformed to interleukin-3 independent growth by retroviral transduction and expression of p210bcr/abl.

Current evidence suggests that the expression of the tyrosine kinase p210bcr/abl in chronic myelogenous leukemia (CML) may directly induce the initial phase of granulocytic hyperplasia. However, the dysregulation of additional genes appears to be required for transition to the acute leukemic phase, as inferred by the appearance of recurrent secondary cytogenetic abnormalities in the majority of patients. To determine whether the expression of p210bcr/abl alone is responsible for this genetic instability, we introduced and expressed the bcr/abl gene from a retroviral vector in a clone of the interleukin-3 (IL-3) dependent myeloblastic 32D C13(G) cell line. Clonal and polyclonal cells transformed to IL-3 independent growth were observed for a period extending up to 6 months for changes in the expression of p210bcr/abl, cell proliferation, inhibition by prostaglandin E1 (PGE1), forskolin, and cyclic adenosine monophosphate (cAMP) analogues, regulation of the cell cycle, and karyotype. Whereas the properties of control vector infected 32D C13(G)' cells remained stable over time, cells expressing p210bcr/abl were phenotypically unstable. In cells expressing p210bcr/abl, we observed selective modulation of p210bcr/abl mRNA and protein expression, evolution from partial to full abrogation of IL-3 dependence, reduced serum requirements, increased cell proliferation, decreased inhibition by PGE1 and cAMP analogues, and the appearance of new structural and numerical chromosomal abnormalities with successive cell passages. These results indicate that expression of p210bcr/abl can directly predispose 32D C13(G)' cells to genetic instability, promotes the emergence of clones with an increased proliferative advantage, and may represent an in vitro model suitable for the study of mechanisms underlying progression to the acute leukemic phase in CML.

Aneuploidy↗
PubMed1992

Cardiac expression of polysialylated NCAM in the chicken embryo: correlation with the ventricular conduction system.

The neural cell adhesion molecule (NCAM) and its polysialic acid moeity (PSA) affect cellular interactions during the development of the nervous system and skeletal muscle. NCAM has also been identified in the embryonic heart of various species including humans. However, knowledge regarding the role of NCAM and its function-modulating PSA in cardiogenesis is limited. The distribution of NCAM and its PSA in the ventricular myocardium of chicken embryos was determined by indirect immunofluorescence staining. The NCAM polypeptide was found throughout the cardiac myocardium. In contrast PSA was located in discrete regions in stage 20 to 44 embryos (during and after septation). Myocardium at the subendocardial regions of the atrioventricular canal and ventricular trabeculae were PSA positive by stage 20. At later stages, transverse sections of the postseptation heart just below the level of the atrioventricular interface revealed a PSA-positive bundle of myocardium in the septum. This bundle was continuous with two branches at a more apical level which in turn were continuous with the PSA-positive subendocardial myocardium lining the left and right ventricles. This pattern of PSA in the myocardium was similar to that of the ventricular conduction system configuration defined in the adult heart. Electron micrographs of the subendocardium of the ventricular septum revealed PSA positivity on myofibril-containing cells with the ultrastructural location of Purkinje fibers. At later stages (35-44) a subset of cells within PSA-positive regions was stained by an antibody against an isoform of the myosin heavy chain found in adult Purkinje fibers. These cells and surrounding tissue lacked PSA in the adult heart. Thus polysialylated NCAM may be modulating cell-cell interactions during the development of the ventricular conduction system.

Animals↗
PubMed1984

[Detection of induced enzyme secretion from neutrophilic granulocytes in the human--a marker of cell activation].

A simple, effective method with an objective analysis for the detection of induced, i.e. not cytotoxic release of enzymes from human neutrophils (PMN) is described. As marker enzyme for lysosomes we determined lysozyme activity and as indicator of cell damage the lactatdehydrogenase activity. The PMN were isolated from peripheral blood. Latex-, zymosan particles and inactivated mycobacteria for phagocytosis model, and heat aggregated human IgG and surface-bounded immune complexes for the Fc-receptor-mediated activation were used as stimulators of enzyme secretion. With these substances we could show an increase of secretion referring to unaffected control in all tested probands. The spontaneous and also the induced secretion are influenced by strong individual variations. It is accentuated, that also without influence of cytochalasin B this process is representable and that this is the supposition to carry out functional tests with PMN under extensively physiological conditions.

Antigen-Antibody Complex↗
PubMed1984

[The lysozyme liberation test--a method for the demonstration of stimulation of human neutrophil granulocytes and monocytes].

A method for proof of induced secretion of lysozyme as a marker of lysosomal enzymes is described. Secretory cells are neutrophil granulocytes and monocytes. The stimulation of the cells is affected by soluble inductors. We used phytohemagglutinin (PHA), Concanavalin A (Con A), purified protein derivates (PPD) and lipopolysaccharide (LPS). Myelin basic protein has a direct stabilizing action on the membrane of lysosomes and induces an increased secretory reaction of cells after irritation. That is why it is recommended to add this substance as a supplement to the culture medium of the test. The optimal incubation parameters for the lysozyme release assay are ascertained. The method is recommended to apply in the fundamental investigation, for testing of stimulating or antiphlogistic agents and in the clinical functional diagnosis.

Adolescent↗
PubMed1983

Expression of immunoglobulin-cross-reactive molecules by neoplastic human T cells. I. Surface detection and isolation of molecules reactive with chicken anti-F(ab')2, anti-alpha and anti-mu antibodies.

There is evidence that the T-cell antigen receptor is immunoglobulin-related and that normal human T cells express surface determinants which cross-react with chicken anti-F(ab')2, anti-alpha and anti-mu antibodies. Surface marker study of six neoplastic human T cell lines suggested that F(ab')2- and mu-cross-reactive determinants may be expressed independently of alpha-cross-reactive determinants. F(ab')2-cross-reactive materials--F(ab')2-CRMs--were then isolated from several T-cell lines and analysed by reverse passive haemagglutination and in immunoprecipitation experiments by polyacrylamide disc gel electrophoresis in buffers containing sodium dodecyl sulphate (SDS-PAGE) under reducing conditions. It was shown that MOLT-4- and CCRF-CEM-derived F(ab')2-CRMs differ serologically and that alpha- are indeed expressed independently of F(ab')2- and mu-cross-reactive determinants. The F(ab')2-CRMs were shown to be T cell-derived, to express determinants similar to or identical with F(ab')2-cross-reactive determinants expressed in normal T-cell membranes and to correspond closely to T-cell antigen binding molecules. Evidence was also obtained that the two F(ab')2-CRMs differ from one another in molecular weight. SDS-PAGE under non-reducing conditions of MOLT-4- and CCRF-CEM-derived F(ab')2-CRMs identified major components of mol. wt. 135,000 and mol. wt. 330,000 respectively. Immunoprecipitation of 125I-labelled F(ab')2-CRMs by chicken anti-F(ab')2 followed by SDS-PAGE under reducing conditions identified major components of mol. wt. 80,000 and mol. wt. of 51,000 from CCRF-CEM-derived F(ab')2-CRMs and tentatively identified components of mol. wt. 52,000 and mol. wt. 23,000 from MOLT-4-derived F(ab')2-CRMs.

Animals↗
PubMed1983

[Detection of stimulator-induced cytotoxicity of human mononuclear cells in short-term culture].

A new test modification for the detection of stimulant-induced cytotoxicity of human mononuclear blood cells is described. Papain-treated human erythrocytes were used as indicator cells. The effector cells were lymphocytes. The ratio of target cells to effector cells was 10/1. Haemoglobin as a marker of lysis of the erythrocytes, released in the supernatant, was measured quantitatively in form of its pseudoperoxidase-activity. PHA, ConA and tannic acid were ascertained and tested as stimulants of cytotoxicity. The reaction was inhibitable by anti-human-lymphocyte-globulin. The test conditions were optimized in regard to incubation time, -temperature, -vessels, culture medium and target cells. The technique is easy to manipulate, has only slight pretensions to the equipment of the laboratory and appears to be very effective. We recommend to apply this method of stimulant-induced cytotoxicity within the detection of the immune state, especially in the progress of immunopathological diseases and the analysis of efficiency of immunosuppressive therapy.

Cells, Cultured↗
PubMed1982

[Dye exclusion test and LDH release assay (author's transl)].

Trypanblue exclusion test and LDH release assay were compared concerning correlation and sensitivity. Short time cultures (4 h; 37 degrees C) of human blood leucocytes were carried out in the presence of various doses of either different tissue extracts or digitonin and assayed by the described methods. Three different reaction types have been found: 1. synchronic type: In dependence on the used antigen the LDH release and the number of coloured cells both show either an analogous dose-dependent positive tendency or a negative reaction. 2. asynchronic type: In this case the trypanblue exclusion test shows negative results. In contrast an increase of LDH release is determined suggesting a permeability-increasing influence of the used substance. 3. stabilization type: In comparison with the control the release of LDH is clearly suppressed up to a definite concentration of the substance. The trypanblue exclusion test is not able to detect this cell stabilizing effect. The LDH release assay is sensitive, objective and in the case of an automatic measurement very effective. A necessary presumption for the test is the absence of LDH or enzyme activity-influencing factors in the substance itself. Reasons for the three types of reaction were discussed. It is recommended to apply this enzyme release assay to methods basing on cellular in-vitro short-time-cultures of nucleic cells (testing of pharmaca, potential antigens or allergen preparations and bio-materials).

Cell Survival↗
PubMedDate not supplied

Reorganization is the key to economical ambulatory health care.

The ambulatory health care program presented here has been created using personnel previously employed in the system. Through planning, reorganization, and an evaluation system, a health care program has been developed that has demonstrated both improved care for clients and professional growth for personnel. Health care services are offered at no increase in cost to the provider.

Ambulatory Care↗