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Biomedical subjects

G Becker

Publications and source records attributed to G Becker.

At least 253 records · Page 14Linked to original sources
PubMed1988

Potentiation of leukotriene production following sequestration of neutrophils in isolated lungs: indirect evidence for intercellular leukotriene A4 transfer.

Granulocyte (polymorphonuclear leukocyte, PMN) sequestration in the microvascular bed with release of different mediators has been implicated in the pathogenesis of inflammatory and allergic disorders in many organs including the lung. In the present study, we investigated the profile and quantity of leukotriene (LT) generation in isolated blood-free perfused rabbit lungs, in isolated PMNs in vitro and in rabbit lungs, following administration of PMNs, mimicking pulmonary leukostasis. Following stimulation with increasing concentrations of the calcium ionophore A 23137 (0.1 to 2 mumol/L), LTs were detected in the buffer fluid by their chromatographic mobility in different high-performance liquid chromatography (HPLC) systems, by on-line peak spectrum analysis, and by post-HPLC radioimmunoassay (RIA). In isolated lungs, a dose-dependent generation of cysteinyl LTs greater than LTB4, in the complete absence of omega-oxidation products of LTB4 as well as nonenzymatic hydrolysis products of LTA4, was evoked. PMNs in vitro showed a typical profile of LT liberation (LTB4, 20-OH-, and COOH-LTB4, nonenzymatic LTA4 metabolites). In the model of pulmonary leukostasis, the presence of omega-oxidation products of LTB4 indicated metabolic integrity of the trapped PMNs. Nonenzymatic hydrolysis products of LTA4 were, however, not detected in the combined system, whereas the cysteinyl LTs increased markedly. This profile suggests intercellular transfer of PMN-derived LTA4 to lung cells in the microenvironment. In addition, at 2 mumol/L A23187, the sum of all LTA4-derived products surpassed the arithmetic sum of the isolated preparations more than threefold. This potentiation of an LT generation under conditions of pulmonary leukostasis may be of biologic significance for amplification of inflammatory events.

Animals↗
PubMed1988

Plasma exchange in dermatomyositis/polymyositis: beneficial effects in three cases.

We describe ameliorative effects of plasmapheresis in three patients with dermatomyositis-polymyositis resistant to other therapy, particularly prednisolone. Serologically, the cases were marked, respectively, by a weakly-reactive speckled-type ANA; a strongly reactive speckled-type ANA and an unidentifiable precipitin line by CIEP; and an antibody to cytoplasm and to Jo1. The remission induced by plasmapheresis was temporary in one case and lasting, with low doses of prednisolone, in two. The nuclear autoantibody in case two became undemonstrable after plasmapheresis but recurred during a subsequent relapse. This experience with plasmapheresis in myositis supplements a substantial reported experience of benefit from this therapy.

Adult↗
PubMed1987

Arachidonic acid lipoxygenase pathways and increased vascular permeability in isolated rabbit lungs.

Products of arachidonic acid (AA) pathways have repeatedly been implicated in acute lung vascular injury with respiratory distress. In blood-free perfused isolated rabbit lungs, AA endogenously released or exogenously applied causes an acute pressor response, mediated by metabolites of the cyclooxygenase pathway including thromboxane A2. Moreover, bolus application of AA (final concentration, 100 microM in the recirculating buffer) during an acute hydrostatic challenge was recently noted to cause a rapid, severalfold increase in the capillary filtration coefficient (Kf,c), though any significant rise in pulmonary vascular pressure was inhibited by indomethacin. In the present study, we showed that during this mode of AA bolus application in cell-free perfused rabbit lungs, microgram amounts of peptidoleukotrienes (LTE4 greater than LTC4 greater than LTD4) and LTB4 were released into the recirculating buffer within 5 min and continued to be released even after 2 exchanges of the perfusion fluid. In the presence of 2 structurally unrelated lipoxygenase inhibitors (nordihydroguaiaretic acid and AA-861), the leukotriene release was nearly completely inhibited and the AA-induced severe increase in vascular permeability was significantly reduced (2.5- to 3-fold rise in Kf,c, compared to a greater than 10-fold increase in Kf,c in the absence of lipoxygenase inhibition). Exogenous LTC4 caused a dose-dependent, sustained pressure rise in protein-free perfused lungs, apparently mediated via the pulmonary generation of AA cyclooxygenase products. Bolus application of 10 micrograms LTC4 or LTD4 or 7.5 micrograms LTB4 in protein-free perfused lungs during an acute hydrostatic challenge did not, however, mimic the AA bolus-induced severalfold increase in vascular permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The hemodynamics of beta-blockade in patients undergoing abdominal aortic aneurysm repair.

To assess the intraoperative and postoperative hemodynamic effects of beta-blockade and its benefits in limiting myocardial ischemia and infarction, a group of 32 patients scheduled for abdominal aortic aneurysm (AAA) surgery (group 1) was treated with oral metoprolol immediately before surgery and with intravenous metoprolol during the postoperative period. Mean age was 71 years, and mean ejection fraction was 56% (range 36% to 83%). Eight patients had a preoperative history of angina, 13 had a history of myocardial infarction, and five had electrocardiographic evidence of prior myocardial infarction. A group of 51 closely matched patients with AAA who did not receive metoprolol served as controls (group 2). In group 1, overall hemodynamic tolerance of metoprolol intraoperatively and postoperatively was good, and there was no incidence of congestive heart failure, hypotension, or asthma. Furthermore, in group 1 significant reduction of systolic blood pressure and heart rate was consistently noted at frequent intraoperative intervals and for 48 hr after surgery, with only a transient reduction of cardiac index. In group 1, only one patient (3%) suffered an acute myocardial infarction. In contrast, nine group 2 patients (18%; p less than .05) suffered perioperative myocardial infarction. Furthermore, only four (12.5%) group 1 patients developed significant cardiac arrhythmias as opposed to 29 group 2 patients (56.9%; p less than .001). These data demonstrate that beta-blockade with metoprolol is effective in controlling systolic blood pressure and heart rate both intraoperatively and postoperatively in patients undergoing repair of AAA and can significantly reduce the incidence of perioperative myocardial infarction and arrhythmias.

Aged↗
PubMed1986

Stroke: health care on the periphery.

A study of decision-making among health providers who work with stroke patients provided information concerning stroke rehabilitation ideology and practice. Data collected from 32 professionals on the meaning of rehabilitation in relation to stroke revealed that stroke rehabilitation is considered to be on the periphery of American health care. Three factors contribute to the peripheral status of stroke rehabilitation: the health care system devalues rehabilitation; stroke rehabilitation differs from acute care medicine; and stroke is viewed as a geriatric problem.

Attitude of Health Personnel↗
PubMed1986

Leukemic macrocheilitis associated with hairy-cell leukemia and the Melkersson-Rosenthal syndrome.

Specific cutaneous infiltrates in hairy-cell leukemia have distinctive histopathologic and histochemical findings. The true incidence of leukemia cutis in hairy-cell leukemia is uncertain, however, because reports often fail to document these distinctive features. A case of leukemic macrocheilitis associated with hairy-cell leukemia and the Melkersson-Rosenthal syndrome is presented. The Melkersson-Rosenthal syndrome is a clinically defined entity composed of Bell's palsy, macrocheilitis, and lingua plicata. Granulomatous cheilitis is often seen on histopathologic examination of the swollen lip tissue; in some cases, however, the findings may be nonspecific. Neoplastic macrocheilitis has not been reported in Melkersson-Rosenthal syndrome. Furthermore, leukemic macrocheilitis has not been reported in hairy-cell leukemia. A possible relationship between these entities is proposed.

Aged↗
PubMed1985

Specific antibodies elicited by antigen covalently linked to a synthetic adjuvant.

S-(2,3-Bis(palmitoyloxy)-(2RS)-propyl)-N-palmitoyl-(R)-cysteinyl-( S)-serine (Tripam-Cys-Ser), a synthetic analogue of the N-terminal part of bacterial lipoprotein, constitutes a potent B-lymphocyte activator, inducing mitosis and immunoglobulin production, and is an adjuvant of the humoral immune response. The product was covalently coupled to a nonimmunogenic oligopeptide, representing an extracytoplasmic sequence of the receptor for the epidermal growth factor (EGF-R amino acids 516-529: Asn-Leu-Leu-Glu-Gly-Glu-Pro-Arg-Glu-Phe-Val-Glu-Asn-Ser). The resulting conjugate was able to induce a specific antibody response 2 wk after a single i.p. administration in mice, as measured by ELISA assays. Controls performed by injecting either adjuvant or oligopeptide alone, or a mixture of both compounds, elicited only a marginal stimulation of the specific antibody response. The conjugate was also immunogenic in vitro. Synthetically derived lipopeptides, thus, constitute powerful agents for turning substances of low immunogenicity into potent immunogens, after conjugating them covalently to the adjuvants. This technique should have a wide application in the preparation of conventional and monoclonal antibodies, as well as for the design of synthetic vaccines.

Adjuvants, Immunologic↗
PubMed1985

The cellular infiltrate in the liver in auto-immune chronic active hepatitis: analysis with monoclonal antibodies.

The mononuclear cell infiltrate in the liver was analyzed, using a panel of monoclonal antibodies (MAbs) of known specificity, in 10 patients with auto-immune chronic active hepatitis and, for contrast, in 14 with other types of chronic parenchymal liver diseases. In all cases, the mononuclear cell (MNC) infiltrate in the liver consisted mostly of T lymphocytes. Helper (Th) cells were more frequent than suppressor/cytotoxic T cells (Tsc) in the portal tracts and cirrhotic scar tissue, while Tsc were more common in the hepatic parenchyma. The number of Tsc cells in the parenchyma was greatest in patients with histologically active CAH and least in patients with quiescent cirrhosis. "Plasmacytoid" cells with the morphology of plasma cells, a hallmark of the MNC infiltrate in auto-immune CAH, were more frequent in histologically active CAH than in quiescent cirrhosis. These plasmacytoid cells were T200 + ve, and hence of bone marrow origin, but the majority expressed neither membrane nor cytoplasmic immunoglobulin nor any lineage-specific marker antigens, and hence did not fulfil criteria for B lymphocytes; however, these cells were positive for OKT10 and HLA DR. No difference was evident between the MNC infiltrate in the liver in auto-immune CAH and that in the other acute or chronic liver diseases studied, including HBV-associated CAH; hence immunohistological studies do not point to any pathological processes uniquely responsible for the pattern of hepatocyte damage seen in auto-immune CAH.

Antibodies, Monoclonal↗
PubMed1985

Relation between antral motility and gastric emptying of solids and liquids in humans.

Our aim was to test the hypothesis that there is a relation between antral phasic pressure activity and the emptying of solids and liquids from the intact human stomach after a mixed meal. This hypothesis was evaluated in 14 healthy individuals in whom we performed simultaneous antral manometry and radioscintigraphy after ingestion of a meal labeled with [99mTc]sulfur colloid in cooked egg (solid component) and [111In]DTPA (liquid component). Analysis of the data included an in-depth evaluation of different models for expressing both gastric emptying rates and antral pressure activity. We found that gastric emptying was adequately represented by a two-phase model consisting of lag and emptying periods and by a power exponential model for the liquid phase. Distal antral motility was accurately represented by the slope of the cumulative antral motility index. During the lag period for solids, the antral motility was inversely related to the duration of the lag. During the solid-emptying period, there was a positive correlation between emptying of solids and antral motility. No significant relation was found between antral motility and overall emptying of the liquid phase of the meal. However, a relationship was found when antral motility was related to liquid emptying after an initial lag period for solids. These human data are consistent with a role of antral pressure activity in trituration of solid food and a role of the antrum in the subsequent propulsion of solids and liquids from the stomach.

Adult↗
PubMed1984

[Prevention of motion sickness with a transdermal therapeutic system containing scopolamine. A randomized, comparative double-blind study in the German Federal Navy].

To test the prophylactic value of anti-motion sickness drugs, a randomized double-blind trial was undertaken on 46 young, healthy, male volunteer marines. Comparison was made between a transdermal therapeutic system (TTS) containing as the effective agent scopolamine (TTS-scopolamine) and proprietary meclozine tablets. An artificial "sea voyage" served to produce motion sickness, each subject sitting by himself on an artificially tilting "island", on two days for 30 minutes. Without treatment, 19 of the 46 subjects developed symptoms of motion sickness requiring treatment. After administration of TTS-scopolamine or meclozine tablets (double-dummy technique) the motion sickness score was reduced by 89% and 59%, respectively. There was a reduction on the visual analog scale of 98% and 59%, respectively. Probability of error (Fisher's exact probability test) for assuming therapeutic advantage of TTS-scopolamine over meclozine tablets was 13.5%. A pre-set significance level of 5% was thus not reached. This trial shows that TTS-scopolamine, even in a brief exposure, has at least the same effectiveness as meclozine, in addition to avoiding the gastrointestinal tract and maintaining with certainty a constant blood level over three days.

Administration, Topical↗