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Biomedical subjects

G Alber

Publications and source records attributed to G Alber.

At least 19 recordsLinked to original sources
PubMed1993

Differential signaling through the Ig-alpha and Ig-beta components of the B cell antigen receptor.

The B cell antigen receptor is a complex containing the antigen-binding immunoglobulin molecules and the Ig-alpha/Ig-beta heterodimer which presumably connects the B cell antigen receptor to intracellular signaling components. To analyze the functional properties of the cytoplasmic parts of the B cell antigen receptor, we used the K46 B lymphoma line (IgG2a, kappa) to express chimeric molecules composed of the extracellular and transmembrane part of the CD8 alpha molecule and the cytoplasmic sequence of either the Ig-alpha (CD8 alpha/Ig-alpha), the Ig-beta (CD8 alpha/Ig-beta) protein or the membrane-bound gamma 2a heavy chain (CD8 alpha/gamma 2a). From these three types of chimeric molecules only (CD8 alpha/Ig-alpha and CD8 alpha/Ig-beta, but not CD8 alpha/gamma 2a, could transduce signals, thus providing the first evidence that the cytoplasmic tail of Ig-alpha and Ig-beta have a signaling capacity. After cross-linking with anti-CD8 alpha antibodies, both molecules induced a similar increase in intracellular free calcium ion and in MAP kinase phosphorylation. Protein tyrosine kinases, however, were strongly activated via the CD8 alpha/Ig-alpha and only marginally via the CD8 alpha/Ig-beta molecule. This suggests that the Ig-alpha and Ig-beta proteins have distinct roles during signal transduction through the B cell antigen receptor.

Amino Acid Sequence↗
PubMed1992

Functional comparison of Fc epsilon RI, Fc gamma RII, and Fc gamma RIII in mast cells.

The cellular responses initiated by cross-linking rodent Fc gamma RII-b1, Fc gamma RII-b2, Fc gamma RIII, and Fc epsilon RI in mast cells were compared. Individual murine Fc gamma R isoforms were transfected into rat basophilic leukemia cells and after cross-linking the FcR, changes in the phosphorylation of protein tyrosines, in the level of intracellular Ca2+, in the hydrolysis of phosphoinositides, and in the release of arachidonic acid metabolites and hexosaminidase were monitored. Cross-linking of Fc gamma RIII initiated all of these early and late biochemical functions, and although they were quantitatively somewhat smaller, the responses were qualitatively indistinguishable from those stimulated by the endogenous Fc epsilon RI. However, despite ample expression, neither Fc gamma RII-b1 nor Fc gamma RII-b2 stimulated these functions when cross-linked. The functional differences between Fc gamma RII and Fc gamma RIII were studied further by assessing the responses to cross-linking of the endogenous Fc gamma R (Fc gamma RII-b1, Fc gamma RII-b2, and Fc gamma RIII) on P815 mouse mastocytoma cells that had been transfected with normal or functionally defective Fc epsilon RI. Two types of mutant subunits had previously been observed to impair the activity of Fc epsilon RI: gamma-chains missing the cytoplasmic domain, and beta-chains missing the COOH-terminal cytoplasmic domain. In both types of transfectants the functional inhibition of the endogenous Fc gamma R paralleled that of the transfected Fc epsilon RI. These results are consistent with the gamma subunit being associated with the functions of Fc gamma RIII as well as of Fc epsilon RI. The functional results also complement the recently reported evidence that Fc gamma RIII can interact with Fc epsilon RI beta-subunits (J. Exp. Med. 175:447, 1992).

Animals↗
PubMed1992

Interaction of aggregated native and mutant IgE receptors with the cellular skeleton.

When aggregated, cell surface proteins become resistant to solubilization by detergents, presumably because of aggregation-induced or -stabilized interactions between the membrane protein and the cytoskeleton or plasma membrane skeleton. We genetically engineered variants of the tetrameric high-affinity receptor for IgE (Fc epsilon RI) to identify a site on its alpha, beta, or gamma chains that mediates such putative interactions. Using flow cytofluorometry, we studied rat basophilic leukemia cells, transiently transfected COS cells, and stably transfected P815 cells bearing wild-type and mutated receptors. We observed that (i) solubilization was markedly dependent on the degree of aggregation, the extent varying somewhat with the cell type and, particularly at lower levels of aggregation, with the time after addition of detergent; (ii) truncation of no single cytoplasmic domain of the alpha, beta, or gamma chains ablated the insolubilization effect; and (iii) incomplete receptors were also efficiently insolubilized by aggregation. Thus receptors consisting only of alpha and gamma chains, a "receptor" consisting of only the ectodomain of the alpha chain attached to the plasma membrane by a glycosyl-phosphatidyl inositol anchor, and "receptors" consisting only of minimally modified gamma chains were resistant to solubilization after aggregation. We conclude that no unique subunit or domain of Fc epsilon RI mediates the insolubilization phenomenon. Our results support a model in which the bridging of membrane proteins leads to their becoming nonspecifically enmeshed in a network of membrane skeletal proteins on either the outside and/or the inside of the membrane so that dissolution of the lipid bilayer becomes irrelevant.

Animals↗
PubMed1991

Structure-function relationships in the mast cell high affinity receptor for IgE. Role of the cytoplasmic domains and of the beta subunit.

To define functionally critical regions of the high affinity receptor for IgE (Fc epsilon RI), we stably transfected P815 cells with mutated cDNAs coding for subunits with truncated cytoplasmic domains (CD). In addition, to examine further the role of the beta subunit, stable transfectants expressing chimeric Fc epsilon RI without beta subunits were generated. Transfectants were tested for receptor-mediated changes in intracellular Ca2+, for stimulated hydrolysis of phosphoinositides, and for protein tyrosine phosphorylation. In all cases these biochemical signals were affected coordinately, suggesting that they are coupled, possibly in a single pathway. Truncation of the alpha subunit or of the NH2-terminal CD of the beta subunit had no effect, but Fc epsilon RIs with beta subunits missing the COOH-terminal CD were inactive. Interestingly, receptors in cells transfected only with human Fc epsilon RI(alpha) (which utilize the gamma chains endogenously synthesized by the P815 cells but which contain no beta subunits) responded normally. Therefore, the beta subunit influences the functions studied but is not essential. Although structural analysis excluded a straightforward mechanism, truncation of the CD of the gamma chain led to loss of signaling.

Animals↗
PubMed1990

Transmembrane signaling in P815 mastocytoma cells by transfected IgE receptors.

In order to delineate structural-functional relationships of the mast cell receptor for IgE (Fc epsilon RI) by molecular-genetic analysis, a transfectable cell must be identified which resembles mast cells except for being deficient in receptors. We have found that the well known murine mastocytoma P815 is suitable. These cells express no Fc epsilon RI, lack mRNA for the alpha and beta subunits of the receptor, but contain some mRNA for gamma chains. After transfection with the cDNA for each of the subunits, stable clones could be isolated which expressed several hundred thousand normal Fc epsilon RI and synthesized large amounts of mRNA for alpha, beta, and gamma, the last at 3-fold higher levels than in the untransfected cells. Aggregation of the transfected receptors led to opening of presumptive calcium channels and to activation of phospholipase C, phospholipase A2, and protein kinase C. The kinetics and other characteristics of the signals were similar to those observed after stimulation of the rat tumor mast cells from which the receptor genetic material had been derived but were smaller in magnitude. These weaker signals most likely result from an overall reduced reactivity exhibited by the P815 cells since stimulation by other ligands led to weaker or even no responses. The cells failed to degranulate after either receptor aggregation or reaction with ionophores with or without phorbol ester. Both the transfected and untransfected P815 cells express Fc receptors for IgG (Fc gamma RII) which, interestingly, independently triggered similar responses despite their apparently simpler subunit structure.

Animals↗
PubMed1990

Relationship between enterotoxic- and T lymphocyte-stimulating activity of staphylococcal enterotoxin B.

The enterotoxins produced by Staphylococcus aureus cause a gastrointestinal intoxication probably via their action on intramucosal neuronal cells. Staphylococcal enterotoxins are also the most powerful mitogens known, activating CD3+ T lymphocytes of several species in a clonally variable and MHC class II-dependent fashion. We examined a possible relationship between enterotoxic and mitogenic activity of staphylococcal enterotoxin serotype B (SEB). We used a monoclonal anti-Id directed against the combining site of an anti-SEB mAb. This anti-Id failed to elicit an enteric response by itself but could block the enteric response in monkeys to a 6000-fold excess of SEB. The anti-Id was mitogenic, however, for human and monkey T cells, triggering a fraction of CD4+ and CD8+ T cells. Not all SEB-reactive T cells were activated by the anti-Id. The anti-Id bound to T cells with a similarly low affinity as did SEB. Additional evidence for a separation of enterotoxic and mitogenic activity comes from studies with carboxymethylated SEB. Although this modified SEB had lost its enterotoxic activity, it was as mitogenic as the unmodified molecule. These results support the notion that the enteric reaction to SEB is not mediated via its effect on T lymphocytes. We conclude that SEB and anti-Id might bind to a common structure of different receptors on T cells and target cells in the intestinal mucosa, probably peripheral sensory neurons.

Animals↗
PubMed1989

Role of substance P in immediate-type skin reactions induced by staphylococcal enterotoxin B in unsensitized monkeys.

The staphylococcal enterotoxin B (SEB)-induced immediate-type skin reaction in unsensitized monkeys was used as a nonimmunologic mast cell stimulation to search for possible involvement of local neural mechanisms. Evidence is presented that substance P (SP) plays a predominant role in mediating intradermal SEB challenge in unsensitized monkeys. With a rabbit SP antiserum directed against the C-terminal region of SP, a concentration-dependent inhibition of SEB-induced skin reactivity could be demonstrated. Furthermore, a rabbit antiserum directed against the mast cell activating N-terminal part of SP was capable of impeding SEB-induced skin reactions totally. By use of SP antagonists, significant reduction of skin reactions evoked by SEB was found. Finally, capsaicin pretreatment of the skin caused a substantial inhibition of SEB-induced skin reactivity. These data suggest that SEB exerts its effect on cutaneous mast cells via stimulation of primary sensory neurons that contain SP. Moreover, a new in vivo model is described for studies of nerve-mast cell interactions.

Animals↗
PubMed1989

Rupture of guide wire during percutaneous transluminal coronary angioplasty. Mechanics and management.

Two rare cases of rupture of the guide wire during percutaneous transluminal coronary angioplasty are described. Both patients required emergency surgical retrieval of the retained fragments and myocardial revascularization. The possible mechanics of the event and the options in the management are discussed with a review of the literature on this rare complication of percutaneous transluminal coronary angioplasty.

Angioplasty, Balloon↗
PubMed1983

[Transluminal coronary dilatation].

Percutaneous transluminal coronary angioplasty (PTCA) represents in patients with single-vessel disease the treatment of choice. Under adequate precautions the method can be performed with reasonable risk outside of a hospital with cardiac surgical operating rooms.

Angioplasty, Balloon↗
PubMed1981

[Stress-ECG after myocardial infarct. Does myocardial infarct reduce the significance of stress ECG in the diagnosis of severe stenosis of the anterior interventricular ramus, the diagonal ramus and the marginal ramus of the coronary artery].

41 patients with inferior myocardial infarction underwent both exercise stress testing and coronary arteriography. Coronary arteriography of 15 patients showed high-degree stenosis as well as occlusions of the right coronary artery and/or of the R. circumflexus of the left coronary artery alone. In 14 of these 15 cases exercise stress testing showed a normal result, in one case results were abnormal. However, we detected additional high-degree stenosis of R. interventricularis anterior and/or of R. diagonalis and/or of R. marginalis in the other 26 patients. In 22 of these 26 cases exercise stress testing showed an abnormal result, in 4 cases it was normal. Because of a sensitivy of 84,6% and a specificity of 93,3% we can assume, that abnormal results of exercise stress testing suggest additional high-degree stenosis of the RIVA-vessel system in patient after inferior myocardial infarction. Considering an eventual bypass operation it is possible to narrow the indication for coronary arteriography.

Adult↗
PubMed1981

[Oncocytoma of the thyroid gland].

The Huerthle cell tumor is quite frequent in southern Germany; this is shown by examinations of patients from our field hospital for nuclear medicine. Our findings conclude with data presented by Galvan (Salzburg). The certainly quite short observation period shows that Huerthle cell adenomas occur much more frequent than carcinomas, when a Huerthle cell neoplasm is diagnosed cytologically. Our investigations show, that Huerthle cell tumors of the thyroid gland are a not wellknown and rare disease, which necessitates a clear decision as result of the cytological finding as far as necessary surgical measures are concerned. This is probably the only way to improve the efficiency of measures for early diagnosis and treatment of tumors of the thyroid gland. Considering the want of clearness which still exists referring to the dignity of Huerthle cell tumors in our opinion even cases which had been diagnosed as adenomas histologically should be controlled regularly once a year during an observation period of ten years.

Adenoma↗
PubMed1980

[Therapy of myocardial infarction in elderly (author's transl)].

The therapy of myocardial infarction in elderly is submitted to restrictions and modifications especially regarding the selection and dosage of the used agents. Numerous antiarrhythmic agents are tolerated from patients in advanced age only with a reduced dose. The treatment of cardiogenic shock is the more problematic, the fewer is suffered a breakdown of blood pressure from the "central" organs brain, heart and kidneys. A rational therapy, adapted to the advanced age, which includes the application of anticoagulants, too, is outlined and founded.

Aged↗
PubMed1978

[Follow up and treatment of pacemaker-patients in advanced age (author's transl)].

Most of the pacemaker-patients are in the eight decade of life. The continuous follow ups of the patient with a pacemaker system have to reguard the often advanced age, the cardiac basic disease, other concomitant diseases and futhermore technical details of the device, the date of implantation and the expected longevity of the power source. The risk of the patient by pacemaker failure in the underlying rhythm disturbance can be estimated by short extinguish of the pacing activity. The additional medical treatment is determined by the findings and must be adapted to the mentioned circumstances.

Aftercare↗