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Biomedical subjects

G Schuler

Publications and source records attributed to G Schuler.

At least 253 records · Page 14Linked to original sources
PubMed1990

Disappearance of certain acidic organelles (endosomes and Langerhans cell granules) accompanies loss of antigen processing capacity upon culture of epidermal Langerhans cells.

Freshly isolated epidermal Langerhans cells (LC) can actively process native protein antigens, but are weak in sensitizing helper T cells. During culture, when LC mature into potent immunostimulatory dendritic cells, T cell sensitizing capacity develops but antigen processing capacity is downregulated. Processing of exogenous antigens for class II-restricted antigen presentation involves acidic organelles. We used the DAMP-technique to monitor acidic organelles at the ultrastructural level in fresh, as well as cultured, mouse and human LC. We observed that the loss of antigen processing capacity with culture of LC was reflected by the disappearance of certain acidic organelles, namely endosomes (particularly early ones), and the hitherto enigmatic LC granules ("Birbeck Granules"). Our findings support the notion that endosomes are critical for antigen processing and suggest that LC granules might be involved as well.

Animals↗
PubMed1990

["Lupus anticoagulant" in immune hyperthyroidism].

A 56-year-old woman with autoimmune hyperthyroidism (Basedow) whose blood coagulation had at first been normal developed prolonged partial thromboplastin time (PTT) of 48 s and a fall in prothrombin time (Quick value) to 52%. At the same time, total activity of factor VIII was reduced to 18% and factor IX to 16%. These values not having changed after the addition of normal plasma, it is assumed that an acquired inhibitor of plasmatic coagulation was responsible. Such inhibitors were first described in lupus erythematodes and therefore called lupus anticoagulant, but later also demonstrated in other autoimmune diseases.

Autoantibodies↗
PubMed1990

Silent myocardial ischemia as a potential link between lack of premonitoring symptoms and increased risk of cardiac arrest during physical stress.

The risk of cardiac arrest is increased during strenuous physical exercise in patients with stable coronary artery disease (CAD). Because premonitoring symptoms are rarely observed, silent myocardial ischemia may represent the pathophysiological basis for the induction of malignant ventricular arrhythmias. Holter monitoring was, therefore, performed in 40 consecutive patients entering a randomized intervention trial on progression of CAD. In 20 of 21 participants (95%) in the intervention program greater than or equal to 1 episode of silent myocardial ischemia was observed during the initial training session. The mean duration of silent myocardial ischemia per patient was 25 +/- 13 min/hr of training session. During normal daily activity only 5 patients (24%) experienced greater than or equal to 1 episode of silent myocardial ischemia (p less than 0.001) yielding a mean duration of 0.6 +/- 1.3 minutes of silent myocardial ischemia/hr of ordinary activity per patient (p less than 0.001 vs training session). During a control period of 24 hours without exercise training the incidence (33%) and mean duration of silent myocardial ischemia (0.8 +/- 2.1 min/hr/patient) were similar to those during normal daily activity on the day of the training session. During the training session the occurrence of frequent or repetitive ventricular arrhythmias was related to 10 silent myocardial ischemia episodes detected in 5 patients. During normal daily activity in 1 patient only was the onset of malignant ventricular arrhythmias associated with silent myocardial ischemia (p less than 0.05). Conditions and results of the Holter studies in the control group patients were comparable to those of the patients in the intervention group on the day without physical exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1990

Tumor necrosis factor alpha maintains the viability of murine epidermal Langerhans cells in culture, but in contrast to granulocyte/macrophage colony-stimulating factor, without inducing their functional maturation.

Freshly isolated murine epidermal Langerhans cells (LC) are weak stimulators of resting T cells but increase their stimulatory capacity 10-30-fold upon 2-3 d of culture together with other epidermal cells. This maturation of LC is mediated by two keratinocyte products. Granulocyte/macrophage colony-stimulating factor (GM-CSF) maintains viability and increases function. IL-1 alone does not keep LC alive, but when combined with GM-CSF further enhances their stimulatory activity. We have now searched for a cytokine that would keep LC in a viable, but functionally immature state. When LC (enriched to greater than 75%) were cultured in the presence of GM-CSF (2 ng/ml) or murine (TNF-alpha) (plateau effect at 62 U/ml), the recovery of viable LC after 72 h was identical. The LC cultured in murine TNF-alpha, however, were 10-30 times less active in stimulating resting T cells. A series of experiments demonstrated that this phenomenon was not due to the induction of insufficient amounts of GM-CSF, the induction of a suppressor factor, or a toxic effect of TNF-alpha. Interestingly, the observed TNF-alpha activity exhibited a species preference, as human TNF-alpha was not active at comparable doses. We have observed an unexpected effect of TNF-alpha on LC in vitro. Though we found that freshly prepared epidermal cells express TNF-alpha mRNA, further studies are needed to establish whether TNF-alpha plays a role in vivo by keeping resident LC in a viable, but functionally immature state.

Animals↗
PubMed1990

"Intravascular lymphomatosis" (angioendotheliomatosis): evidence for a T-cell origin in two cases.

Intravascular lymphomatosis (IL) is a rare and potentially fatal multifocal intravascular proliferative disorder, most often involving the skin and the central nervous system. Originally considered an endothelial disorder, IL has recently been reclassified as an angiotropic lymphoma, most often of B-cell origin. We report immunocytochemical and ultrastructural findings in two patients with IL, both representing angiotropic T-cell lymphomas. In one patient, lesional tissue was examined by Southern blot analysis and monoclonal T-cell receptor rearrangement was found. As an additional feature in one patient, a myelosuppressive serum factor was demonstrated in peripheral blood progenitor cell cultures as the cause of underlying chronic anemia and leukopenia; this factor is thought to be a cytokine product of the lymphoma cells.

Aged↗
PubMed1990

Intravenous carbochromen: a potent and effective drug for estimation of coronary dilatory capacity.

Systemic and coronary haemodynamic effects of carbochromen (0.125 mg kg-1 min-1 for 40 min i.v.) and dipyridamole (0.05 mg kg-1 min-1 for 10 min i.v.) were investigated in 18 patients without detectable heart disease. Both drugs induced a comparable increase in coronary blood flow (carbochromen: from 82 +/- 23 to 337 +/- 68 ml.100 g-1.min-1; dipyridamole: from 78 +/- 9 to 301 +/- 61 ml.100 g-1.min-1). This resulted in a minimal coronary resistance of 0.23 +/- 0.04 mmHg.ml-1.100 g.min for dipyridamole and of 0.24 +/- 0.04 mmHg.ml-1.100 g.min for carbochromen. In response to dipyridamole (n = 12) heart rate increased from 73 to 94 beats min-1 (P less than 0.005) and mean aortic pressure fell from 89 to 78 mmHg (P less than 0.001). After administration of carbochromen (n = 6) no significant systemic effects occurred. Dipyridamole induced a significant increase in myocardial oxygen consumption by 46% (P less than 0.001); after application of carbochromen myocardial oxygen consumption remained unchanged. From these data it can be concluded that for the evaluation of coronary dilatory capacity carbochromen may be more suitable than dipyridamole because (1) maximal coronary vasodilation is induced without changes in myocardial oxygen consumption and (2) no systemic effects occur.

Adult↗
PubMed1990

Use of stroma for the detection of blood-group antibodies by ELISA.

A micro enzyme-linked immunosorbent assay (ELISA), using lyophilized stroma as carrier of red blood cell antigens, which stay stable longer than usual, using intact erythrocytes, was developed for determination of blood-group antibodies in the AB0, Kell and Lewis-systems. Stroma being fixed on microtiter plates was incubated with antisera and peroxidase-conjugated anti-human globulin. The transformation of the substrate added was determined photometrically. A binding of antibodies to the stroma could be demonstrated up to an antibody dilution of 1:1024 for the ABO-system, of 1:512 for the Kell-system and of 1:64 for the Lewis-system. By standardization of this method the quantitative determination of antibodies becomes possible without being restricted by the limited stability of intact erythrocytes.

ABO Blood-Group System↗
PubMed1990

Intravenous thrombolytic therapy with a combination of single-chain urokinase-type plasminogen activator and recombinant tissue-type plasminogen activator in acute myocardial infarction.

The effects of simultaneous intravenous infusions of 12 mg recombinant tissue-type plasminogen activator (rt-PA) over 30 minutes and 48 mg single-chain urokinase-type plasminogen activator (scuPA) over 40 minutes were studied in 38 patients with acute myocardial infarction. Coronary arterial patency was assessed angiographically 60 minutes and 90 minutes after initiation of treatment. Patency was achieved in 19 of 31 patients (61.3%) (95% confidence limits, 42-78%) at 60 minutes and in 27 of 33 patients (81.8%) (95% confidence limits, 65-93%) at 90 minutes. Nonspecific plasminogen activation was monitored by measuring relevant plasma parameters. At 60 minutes and 120 minutes, the fibrinogen concentration decreased slightly to 82.8 +/- 24.3% and 91.2 +/- 17.4% of the preinfusion level, and the plasminogen concentration to 66.3 +/- 15.2% and 65.3 +/- 13.4%, respectively. A greater consumption of alpha 2-antiplasmin was observed, which decreased to 30.7 +/- 22.8% and 32.2 +/- 21.2% of the preinfusion level at 60 and 120 minutes, respectively. No bleeding necessitating transfusion was observed. Two patients (5.3%) died during hospitalization. The findings suggest that the combined intravenous infusion of rt-PA and scuPA at appropriate doses induces highly effective coronary thrombolysis equal to the best results obtained with either rt-PA or scuPA alone. This efficacy is coupled with high specificity. Thus, the data support the potential use of combinations of rt-PA and scuPA in place of monotherapy.

Drug Therapy, Combination↗
PubMed1990

Molecular action of the l(2)gl tumor suppressor gene of Drosophila melanogaster.

Tumor suppressor genes act as recessive determinants of cancer. These genes contribute to the normal phenotype and are required for regulating cell growth and differentiation during development. Inactivation of tumor suppressor genes leads to an unrestricted pattern of growth in specific cell types. In Drosophila, a series of genes have been identified that cause tissue-specific tumors after mutation. Of these, the lethal(2)giant larvae (l(2)gl) gene is the best studied. Homozygous l(2)gl mutations cause the development of malignant tumors in the brain and the imaginal discs. Genomic DNA from the l(2)gl locus has been cloned, introduced back into the genome of l(2)gl-deficient animals, and shown to reinstate normal development. The nucleotide sequence of the l(2)gl gene has been determined, as well as the sequences of two classes of transcripts. Analysis of the spatial distribution of both l(2)gl transcripts and proteins revealed that during early embryogenesis the l(2)gl gene is uniformly expressed in all cells and tissues. In late embryos, the l(2)gl expression becomes gradually restricted to tissues presenting no morphological or neoplastic alteration in the mutant animals. Further mosaic experiments revealed that l(2)gl gene loss can cause three distinct phenotypes: neoplastic transformation, abnormal differentiation, and normal development. These phenotypes depend upon the extent of gene activity in the stem cells prior to the formation of l(2)gl- clones. These analyses indicate that the critical period for the establishment of tumorigenesis occurs during early embryogenesis at a time when the l(2)gl expression is most intense in all cells.

Animals↗
PubMed1990

Dendritic cell production of cytokines and responses to cytokines.

Dendritic cells (DC) are a family of bone marrow-derived MHC class II expressing cells which occur in small numbers in most lymphoid and nonlymphoid tissues. They represent a distinct lineage of leukocytes which can be found in two distinct maturational stages: immature dendritic cells are exemplified by the Langerhans cells in the epidermis, and are considered to be precursors to the mature dendritic cells in the lymphoid organs. These maturational stages can be distinguished by phenotypic and functional characteristics. Immature dendritic cells are weak stimulators of resting T lymphocytes but are excellent in processing soluble protein antigens for presentation to T cell clones. Mature dendritic cells show exactly reciprocal features. In this review the relatively few available data on cytokine production by DC and responses of DC to cytokines are collected. Our goal is to consider the role of cytokines in DC function including the transition from immature to mature stages.

Animals↗
PubMed1989

Insulin abuse in long-standing IDDM.

Two patients with insulin-dependent diabetes mellitus (IDDM) for 42 and 46 years respectively were diagnosed to produce factitious hypoglycemia. They had several properties in common: abnormal personality, refusal to stop incipient hypoglycemia, ideal body weight, good hemoglobin A1c (HbA1c) values, non-specific changes in the EEG, and brain atrophy sparing the periventricular areas. The addiction forced the patients to continue their habit during hospital stay. The dose of surreptitiously injected regular insulin always produced serum insulin concentrations large enough to clarify the diagnosis.

Aged↗
PubMed1989

Gamma irradiation as a substitute for H2O2 in peroxidase-labelled enzyme immunoassays.

The ability of gamma irradiation to substitute for H2O2 in peroxidase-labelled enzyme immunoassays was investigated. Colouring of TMB (3,3',5,5'-tetramethylbenzidine), ABTS [2,2'-azino-di(3-ethylbenzthiazoline-6-sulphonic acid)], and OPD (o-phenylenediamine) was produced with doses of 10 and 20 Gy. Addition of superoxide dismutase enhanced TMB and ABTS, and inhibited OPD. The reaction was terminated when the irradiation was stopped. The use of denaturing compounds to stop the reaction was unnecessary and coated antigens could be re-used for a second immunoassay.

Free Radicals↗
PubMed1989

Murine epidermal Langerhans cells express significant amounts of class I major histocompatibility complex antigens.

Epidermal Langerhans cells (LC) are leukocytes that express major histocompatibility complex (MHC) class II antigens and function as antigen-presenting and accessory cells. Caughman et al. [Caughman, S. W., Sharrow, S. O., Shimada, S., Stephany, D., Mizuochi, T., Rosenberg, A. S., Katz, S. I. & Singer, A. (1986) Proc. Natl. Acad. Sci. USA 83, 7438-7442] reported that LC are deficient in surface expression of MHC class I antigens, implying a specialization of these cells to class II-restricted antigen presentation. To readdress this obviously important issue, we have studied murine epidermal sheets prepared from B6 X BALB/c----B6 bone marrow chimeras 5 months after irradiation and bone marrow reconstitution. This enabled us to distinguish class I of LC from that of surrounding keratinocytes. When sheets were analyzed by immunofluorescence microscopy with monoclonal antibodies specific for donor class I antigens, donor-derived LC but not LC of recipient origin were stained. Appropriate controls for antibody isotype and MHC haplotype were negative. LC in epidermal cell suspensions, prepared from normal BALB/c and BALB/cBy mice (MHC haplotype d), were analyzed by flow cytometry as well as immunofluorescence microscopy. LC were stained by monoclonal antibodies to class I antigens of haplotype d, but not by isotype-matched control antibodies to class I antigens of haplotype k. We also found that LC were virtually depleted from epidermal cell suspensions by treatment with monoclonal antibodies to class I antigens of haplotype d and complement but not by treatment with control monoclonal antibodies and complement. Our data, therefore, show that LC express MHC class I molecules on their surface.

Animals↗
PubMed1989

Cultured human Langerhans cells resemble lymphoid dendritic cells in phenotype and function.

Freshly isolated murine epidermal Langerhans cells (LC) are weak stimulators of resting T cells. Upon culture their phenotype changes, their stimulatory activity increases significantly, and they come to resemble lymphoid dendritic cells. Resident murine LC, therefore, might represent a reservoir of immature dendritic cells. We have now used enzyme cytochemistry, a panel of some 80 monoclonal antibodies, and immunofluorescence microscopy or two-color flow cytometry, as well as transmission electron microscopy, to analyse the phenotype and morphology of human LC before and after 2-4 d of bulk epidermal cell culture. In addition, LC were enriched from bulk epidermal cell cultures, and their stimulatory capacity was tested in the allogeneic mixed leukocyte reaction and the oxidative mitogenesis assay. Cultured human LC resembled human lymphoid dendritic cells in morphology, phenotype, and function. Specifically, LC became non-adherent upon culture and developed sheet-like processes (so-called "veils"), decreased their surface ATP/ADP'ase activity, and lost nonspecific esterase activity. As in the mouse, surface expression of MHC class I and II antigens increased significantly, and FcII receptors were significantly reduced. Markers that are expressed by dendritic cells (like CD40) appeared on LC following culture. Cultured human LC were potent T-cell stimulators. Our findings support the view that resident human LC, like murine LC, represent immature precursors of lymphoid dendritic cells in skin-draining lymph nodes.

Antibodies, Monoclonal↗
PubMed1989

Four-year follow-up study in patients with angina pectoris and normal coronary arteriograms ("syndrome X")

In patients with typical stress-induced anginal pain, normal coronary arteries, and unimpaired left ventricular performance at rest ("syndrome X"), a reduced coronary dilatory capacity, abnormal lactate metabolism during stress, and reduction of left ventricular functional reserve have been described. A group of 40 patients with syndrome X was followed for several years to determine their long-term prognosis. In 27 patients pulmonary artery pressure and in 19 patients left ventricular ejection fraction were reassessed during rest and exercise approximately 4 years after the initial examination. In patients with stress-induced ST-segment depression, these variables did not change during the observation period. In patients with constant or rate-dependent left bundle branch block, however, there was significant deterioration of left ventricular performance during rest (pulmonary artery mean pressure, 16 +/- 3 vs. 17 +/- 4 mm Hg, p = NS; left ventricular ejection fraction, 62 +/- 5% vs. 55 +/- 5%, p less than 0.05) and exercise (pulmonary artery, 30 +/- 6 vs. 39 +/- 10 mm Hg, p less than 0.005; left ventricular ejection fraction, 59 +/- 6% vs. 49 +/- 5%, p less than 0.01). These findings suggest that in syndrome X two subgroups with distinctly different prognoses may be defined: In patients with stress-induced ST-segment depression during exercise, left ventricular performance remains well preserved; however, in patients with either constant or rate-dependent left bundle branch block, there is significant deterioration of left ventricular function within several years.

Angina Pectoris↗
PubMed1989

[Peracute constrictive, idiopathic pericarditis--a case report of an acute life-threatening disease picture].

Generally, idiopathic pericarditis is considered a benign, self-limiting disease. Frequently, the exsudative phase of the disease is followed by a mild form of transitory constriction of the pericardium. The case reported here shows an unusual course of the disease. Shortly after the symptoms of exsudative pericarditis subsided a life-threatening form of pericardial constriction developed within weeks. In case of chronic pericardial constriction perioperative mortality for partial pericardiectomy is not insignificant. This is a result of myocardial damage that is difficult to assess prior to surgery. For that reason a partial pericardiectomy should be attempted as early as possible, even in cases with acute pericardial constriction.

Acute Disease↗