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Biomedical subjects

M Ernst

Publications and source records attributed to M Ernst.

At least 199 records · Page 11Linked to original sources
PubMed1990

Comparison of the reactions of the Rh-related murine monoclonal antibodies BS58 and R6A.

The murine monoclonal antibodies BS58 and R6A are known to recognize epitopes related to the human Rh system: neither antibody reacts with Rhnull cells and the BS58 antigen is not expressed by -D- or .D. cells. It is shown here that the numbers of BS58 and R6A antigen sites vary with Rh phenotype. Both epitopes are well represented on cells of the CDe/CDe, CDe/cDE and CDe/cde phenotypes; BS58 sites are markedly reduced on cde/cde and cDE/cde and are only just detectable on cDE/cDE cells when compared with R6A sites. The number of R6A sites per red cell ranged between 20,000 and 150,000. The evidence indicates that the BS58 epitope is not on the polypeptides carrying D or R6A, nor is it uniquely on one of the polypeptides carrying either C, c, E or e. It is suggested that the BS58 epitope is either common to all the CcED polypeptides or that it is present on a polypeptide which has not yet been identified biochemically.

Animals↗
PubMed1990

Inhibitory and stimulatory effects of Pseudomonas aeruginosa pyocyanine on human T and B lymphocytes and human monocytes.

Pyocyanine, a pigment produced by Pseudomonas aeruginosa, has dual dose-dependent stimulatory as well as inhibitory effects on immune responses in vitro as measured by DNA synthesis of human T and B lymphocytes, interleukin-2 (IL-2) production by human T lymphocytes, immunoglobulin production by human B lymphocytes, and monokine production by human monocytes. In general, stimulatory activity was found at low concentrations of pyocyanine, whereas high concentrations of the pigment resulted in an inhibition of responses. At a pyocyanine concentration of 0.1 micrograms/ml or less the proliferation of T and B lymphocytes was enhanced, but at 0.5 micrograms/ml it was suppressed. IL-2 production by T lymphocytes was enhanced at concentrations up to 0.5 micrograms/ml but totally inhibited at 1.0 micrograms/ml. The differentiation of B lymphocytes to become immunoglobulin-producing cells was also enhanced in the presence of low doses of pyocyanine, whereas secretion of immunoglobulin by B lymphocytes was suppressed at all concentrations of pyocyanine. In contrast to the dual effects of pyocyanine on lymphocyte response, lipopolysaccharide-induced IL-1 and tumor necrosis factor release by monocytes was markedly enhanced by low as well as high concentrations of pyocyanine. From these results we conclude that this property of pyocyanine may lead to suppression of specific defense mechanisms and enhance harmful inflammatory reactions of the host during infection with Pseudomonas aeruginosa.

B-Lymphocytes↗
PubMed1990

Human trk oncogenes activated by point mutation, in-frame deletion, and duplication of the tyrosine kinase domain.

Malignant activation of the human trk proto-oncogene, a member of the tyrosine protein kinase receptor family, has been implicated in the development of certain human cancers, including colon and thyroid papillary carcinomas. trk oncogenes have also been identified in cultured cells transfected with various DNAs. In this study, we report the characterization of three in vitro-generated trk oncogenes, trk2, trk4, and trk5 (R. Oskam, F. Coulier, M. Ernst, D. Martin-Zanca, and M. Barbacid, Proc. Natl. Acad. Sci. USA 85:2964-2968, 1988), in an effort to understand the spectrum of mutational events that can activate the human trk gene. Nucleotide sequence analysis of cDNA clones of trk2 and trk4 revealed that these oncogenes were generated by a head-to-tail arrangement of two trk tyrosine protein kinase domains connected by a purine-rich region. These oncogenes code for cytoplasmic molecules of 67,000 (p67trk2) and 69,000 (p69trk4) daltons. In contrast, the product of the trk5 oncogene, gp95trk5, is a cell surface glycoprotein of 95,000 daltons. This oncogene was generated by a 153-base-pair in-frame deletion within sequences coding for the extracellular domain of the trk receptor. This activating deletion encompasses a triplet coding for one of the nine cysteine residues that the trk receptor shares with the product of the highly related trkB tyrosine protein kinase gene. Introduction of a single point mutation (TGT----AGT) in this codon resulted in a novel trk oncogene whose product, gp140S345, differs from the nontransforming trk proto-oncogene receptor in a single amino acid residue, Ser-345 instead of Cys-345. These results illustrate that multiple molecular mechanisms, including point mutation, internal deletion, and kinase domain duplication, can result in the malignant activation of the human trk proto-oncogene.

Amino Acid Sequence↗
PubMed1990

Increased activity of insulin-like growth factor (IGF) in osteoblastic cells in the presence of growth hormone (GH): positive correlation with the presence of the GH-induced IGF-binding protein BP-3.

Insulin-like growth factors (IGFs) are bound in the circulation to specific binding proteins (BP). The predominant BP is a GH-dependent glycosylated protein of 42-49 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (BP-3), whereas nonglycosylated GH-independent IGFBPs of 32 kDa and less are minor constituents. Primary cultures of rat osteoblastic cells constitutively produce IGFBP species of 32 kDa, while GH induces the accumulation of BP-3. To examine whether BP-3 could regulate the biological activity of IGF-I on osteoblasts, we compared the effects of recombinant native human IGF-I (hIGF-I) on primary cultures of osteoblasts in the presence and absence of GH. hIGF-I stimulated cell replication and alpha 1(I) collagen gene expression in a dose-dependent manner, and these effects were potentiated by the presence of GH, which increased the accumulation of BP-3. To further examine this correlation, we compared the effects of two IGF-I peptides on the osteoblastic cell line PyMS, which constitutively produces BP-3, to those in RCT-3 cells, which do not secrete this IGFBP. Using hIGF-I and [Gln3,Ala4,Tyr15,Leu16]IGF-I ([QAYL]IGF-I), a mutated IGF-I with reduced affinity to IGFBPs, we found that at equimolar concentrations hIGF-I produced higher stimulation than [QAYL]IGF-I on [3H]thymidine incorporation, cell replication, and collagen gene expression in PyMS cells. In contrast, both IGF-I peptides had similar potency in RCT-3 cells. Hence, these data show that the accumulation of BP-3 correlates with enhanced hIGF-I activity on osteoblastic cells, suggesting that BPs may act locally to augment the effects of IGF-I in bone.

Amino Acid Sequence↗
PubMed1990

Monocyte-T-cell interactions in pokeweed mitogen-activated cultures.

Monocyte-T-cell interactions were studied in pokeweed mitogen (PWM)-activated cell cultures. We addressed the question of monocyte changes in PWM-stimulated cultures of T cells and monocytes and found, by flow cytometric analysis, that PWM activation led to a loss of cells with monocyte or macrophage phenotype (CD14, HLA-DR, HLA-DQ) within 48 hr of culture in the presence of T cells (CD4+ T cells), but not in cultures of pure monocytes. Chemiluminescence measurements revealed that phagocytic stimulation of monocytic superoxide release was impaired in PWM-stimulated cultures of monocytes plus T cells, but not in PWM-stimulated cultures of pure monocytes. Furthermore, PWM induced the secretion of interferon-gamma (IFN-gamma) in primary cultures of T cells supplemented with 20% of monocytes, whereas in subsequent secondary cultures of these cells PWM induced IFN-gamma only when monocytes were added. We conclude from these flow cytometric and functional analyses that monocytes are efficiently eliminated from PWM-activated T-cell/monocyte cultures by CD4+ T lymphocytes.

Antigens, Differentiation, Myelomonocytic↗
PubMed1990

[Monoclonal antibodies to antigens of the Rh system].

For the development of monoclonal antibodies, which are useful for typing of Rh-system antigens, human monoclonal antibodies are needed. We have established a method for raising human monoclonal antibodies using EBV-transformation and subsequent stabilisation by fusing with mouse myeloma or heteromyeloma cell-lines. Using this method, we have produced several clones reacting with the D antigen which can be used for typing purposes as well as for research purposes to differentiate epitopes and categories.

Animals↗
PubMed1990

Human monoclonals against erythrocyte antigens.

Mice are not able to respond in making specific antibodies against a variety of human antigens. One of these antigens is the erythrocyte D-antigen of the Rh-system. Until now, it has been possible only to make murine monoclonals against structures of the Rh-proteins. These antibodies were not suitable for routine use in blood grouping. As an alternative, the human immune system is able to produce alloantibodies against Rh-D with high specificity. As a result, with the development of reproducible methods for the generation of human monoclonals, we have started to establish protocols for the production of antibodies against the Rh-D antigen. In addition, we selected a heteromyeloma line, MD33, which is a non-secretor line with high fusion rate giving rise to hybridomas which are high producers. Here, we compare different methods for their efficiency in producing human monoclonals against the Rh-D antigen. We tested the direct fusion of human PBL with either mouse myeloma or human lymphoblastoid cell line, immortalization by EBV-transformation, EBV-transformation followed by fusion with mouse myeloma line, and EBV-transformation followed by fusion with heteromyeloma line. We could demonstrate that most success can be achieved by fusions of EBV-transformed PBL with mouse myeloma line P3X63-Ag8.653 and heteromyeloma line MD33 which resulted in several stable and antigen-specific lines per fusion.

Animals↗
PubMed1990

[Immunologic parameters in lung tuberculosis].

In patients with pulmonary tuberculosis serum immunoglobulin levels are found to be increased, quantitative deviations from the norm are observed on analysis of the mononuclear cells, there is an increase in the number of circulating immune complexes, and, in the event of extensive pulmonary involvement, an attenuation of cell-mediated cutaneous reactions is seen. In accordance with the chronic course of the disease, a return to normalcy of these parameters in the healing phase occurs only gradually.

Antigen-Antibody Complex↗
PubMed1990

[Immunoglobulin G subclass deficiency in patients with asthma and chronic obstructive bronchitis].

In 99 patients with asthma or chronic obstructive bronchitis immunoglobulins and immunoglobulin-G subclasses were measured to characterize the frequency of humoral immune deficiencies. 26 patients had decreased serum levels in one or two IgG subclasses. So IgG-subclass deficiency is a common finding in patients with asthma and obstructive bronchitis. Treatment with corticosteroids seems to promote low IgG-subclass levels, but cannot fully explain alterations of IgG subclasses. Today IgG-subclass deficiencies are regarded as an important factor in the susceptibility to recurrent infections. We think, variation in IgG subclasses may have further effects on the noninfectious inflammatory processes of asthma and obstructive bronchitis.

Asthma↗
PubMed1990

General education in the professional curriculum: faculty perceptions of contributions.

This study investigated general education contributions to the professional development of majors in five selected health professional disciplines from 114 accredited programs. The findings identified that the most important general education contributions to health professional development, as perceived by faculty, included abilities to communicate verbally and in writing, to solve problems, to understand one's own and others' behavior, and to develop a personal value system. Although health professional faculty reported strong satisfaction with the size, content, and contribution of the general education curriculum, there was little collaborative curriculum planning between faculty in professional and general education programs. These latter findings are at odds with national reports lamenting the state of general education. A variety of strategies are described for opening channels of communication between health professional and general education faculty and for integrating general education and professional curricula.

Allied Health Personnel↗
PubMed1990

[Increased serum IgE concentration in lung tuberculosis].

In about one-half of patients with pulmonary tuberculosis, elevations of the IgE serum concentrations are found which, under anti-tuberculous therapy, reveal a tendency to regress. Aetiologically, in addition to an unspecific B-cell activation, a specific reaction of the immune system may be considered.

Adolescent↗
PubMed1989

Distribution of substance P-like, leucine-enkephalin-like, and bombesine-like immunoreactivity and acetylcholinesterase activity in the visual system of salamanders.

In the urodele species Salamandra salamandra and Batrachoseps attenuatus, the distribution of the neuropeptides substance P (SP), leucine-enkephalin (LENK), and bombesine (BOMB) was investigated by means of immunohistochemistry in brain areas containing retinofugal projection sites (tectum mesencephali, praetectum, thalamus) as well as in brain regions postsynaptic to the tectum. The activity of acetylcholinesterase (AChE) was studied histochemically. Despite its simplified, two-layered morphology, the salamander tectum shows a high degree of neurochemical differentiation, characterized by a laminar organization of neuropeptide-like immunoreactivity and AChE-activity comparable to that found in the anuran tectum, which has a multi-layered morphology. SP-like immunoreactivity constituted four tectal laminae, two of them occurring in the stratum opticum. LENK-like immunoreactivity formed three laminae, one in the stratum opticum. BOMB-like immunoreactivity formed one lamina within the stratum opticum and one in the tectal efferent layers. Layers 1 and 2 of the stratum opticum revealed high AChE-activity, whereas low activity was found in deep fiber layers containing tectal efferents. The outer cellular layer also revealed AChE-activity. After enucleation of one eye, the contralateral tectum lacked neuropeptide-like immunoreactivity and AChE-activity in the layers containing retinofugal projection sites. No reduction of immunoreactivity was found in nuclei postsynaptic to the tectum. Our experiments suggest that the secondary simplification that has taken place in salamanders with respect to tectal morphology did not affect the neurochemical differentiation of the tectum.

Acetylcholinesterase↗
PubMed1989

Release of insulin-like growth factor carrier proteins by osteoblasts: stimulation by estradiol and growth hormone.

Osteoblast-like rat calvaria cells release specific insulin-like growth factor (IGF) carrier proteins (CPs). As analyzed by SDS-PAGE under nonreducing conditions, Western blotting and detection by 125I-IGFs, CPs migrating with the IGF-binding subunits of the major CP species of rat serum (42/45/49 kDa) accumulate in cell culture medium. Treatment of the cells with growth hormone and estradiol increases the abundance of this glycosylated CP species. Since the two hormones were previously found to stimulate osteoblast replication via an IGF I-dependent mechanism, the data indicate that hormones may control local IGF action not only by regulating synthesis of IGFs and their receptors but also their presentation by CPs.

Animals↗
PubMed1989

Lipoxygenase inhibitors suppress formation of tumor necrosis factor in vitro and in vivo.

Injection of endotoxin in D-galactosamine sensitized mice resulted in increased serum levels of tumor necrosis factor as determined in a fibroblast cytolysis assay. Concomitant injection of different lipoxygenase inhibitors decreased the titer of TNF. When the lipoxygenase inhibitors were tested in macrophage cultures stimulated with LPS, they prevented the production of TNF. Indomethacin, a blocker of cyclooxygenase was neither in vivo nor in vitro effective in the prevention of the endotoxin-induced synthesis of TNF. The involvement of superoxide anion in this effect was excluded by use of superoxide dismutase which did not influence the formation of TNF in macrophages.

Animals↗
PubMed1989

Monocyte long-term cultivation on microvascular endothelial cell monolayers: morphologic and phenotypic characterization and comparison with monocytes cultured on tissue culture plastic.

Human monocytes were cultured on monolayers of a newly established microvascular endothelial cell strain. As compared to monocytes cultured on plastic, these endothelium-"derived" monocytes (EDM) showed distinct morphology, higher motility, and different antigen-expression pattern for several surface markers, as detected by cytofluorimetry. The MO-1- and the Leu-M1-marker were maintained on EDMs while they were lost on plastic-cultured cells. The MAX 1-26-termed markers failed to increase on EDMs, in contrast to plastic-cultured monocytes. For seven additional markers, expression after two weeks in vitro was higher on EDMs than on plastic-cultured monocytes. Functionally EDMs showed typical monocyte/macrophage behavior and were easily removable from the culture system for further experimentation. Our data suggest that monocytes cultured on microvascular endothelial cells are maintained for several weeks in a more physiologic state than monocytes cultured on plastic.

Animals↗
PubMed1989

Lissencephaly, abnormal lymph nodes, and T-cell deficiency in one patient.

We report on a child with lissencephaly type I, abnormal lymph nodes, and immunodeficiency, associated with recurrent infections, autoimmune disease, spastic tetraplegia, and psychomotor retardation. Diagnostic measures included cranial computer tomography (CT) and magnetic resonance imaging (MRI) scanning, several in vivo and in vitro immunological tests, and histology of skin, lymph nodes, and liver including electron microscopy and immunohistology. Despite medical supervision, the child died at age 4 years. A common pathogenetic mechanism of defective migration of neurons and the dysmaturation of lymph nodes is most probable. The T-cell deficiency may represent a common defect of the development of both neuronal and lymphatic tissue, as the six-layered cerebral cortex and the B-cell areas in lymph nodes develop at about the same gestational age. A common defect could also be assumed involving genetically determined cell surface proteins.

Brain↗
PubMed1989

Evidence for a direct effect of estrogen on bone cells in vitro.

Although the beneficial effects of estrogen in the treatment of postmenopausal osteoporosis are well documented, such effects were difficult to demonstrate in in vitro models. However, recent improvements in bone cell culture models (better defined osteoblastic cell populations, omission of Phenol Red from culture media) enabled several investigators to show albeit small, but reproducible, direct effects of estradiol in various osteoblastic cell types. Such findings were supported by the identification of low numbers of high-affinity estrogen receptors in bone cells derived from different mammalian species. The likely physiological relevance of the in vitro results is indicated by the specificity for 17 beta-estradiol, and the requirement for nanomolar concentrations of the hormone, consistent with a Kd of 0.6 nM for estradiol binding to its receptor [56]. In bone in vitro, estradiol may have anticatabolic effects by decreasing parathyroid hormone responsiveness, and anabolic effects by stimulating matrix synthesis and cell proliferation. Insulin-like growth factor-I is likely to be an autocrine/paracrine mediator for the anabolic effects and may, when associated with its binding proteins, effectively act in the bone compartment.

Animals↗