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G Schuler

Publications and source records attributed to G Schuler.

At least 19 recordsLinked to original sources
PubMed1992

Cytokine gene expression in murine epidermal cell suspensions: interleukin 1 beta and macrophage inflammatory protein 1 alpha are selectively expressed in Langerhans cells but are differentially regulated in culture.

Epidermal Langerhans cells (LC) are considered direct yet immature precursors of dendritic cells (DC) in the draining lymph nodes. Although the development of LC into potent immunostimulatory DC occurs in vitro and has been studied in detail, little is known about their profile of cytokine gene expression. By using reverse transcriptase polymerase chain reaction analysis to screen 16 cytokines followed by Northern blotting for selected analysis, we determined the cytokine gene expression profile of murine LC at different time points in culture when T cell stimulatory activity is increasing profoundly. LC regularly expressed macrophage inflammatory proteins, MIP-1 alpha and MIP-2, and interleukin 1 beta (IL-1 beta). Both MIPs were downregulated upon culture and maturation into DC, whereas IL-1 beta was strongly upregulated in culture. MIP-1 alpha and IL-1 beta mRNA were found only in LC, but not in other epidermal cells. Apart from trace amounts of IL-6 in cultured LC, several macrophage and T cell products were not detected. The cytokine expression profile of LC thus appears distinct from typical macrophages. The exact role of the cytokine genes we found transcribed in LC remains to be determined.

Animals↗
PubMed1992

Identification of proliferating dendritic cell precursors in mouse blood.

While it has been known that dendritic cells arise from proliferating precursors in situ, it has been difficult to identify progenitors in culture. We find that aggregates of growing dendritic cells develop in cultures of mouse blood that are supplemented with granulocyte/macrophage colony-stimulating factor (GM-CSF) but not other CSFs. The dendritic cell precursor derives from the Ia-negative and nonadherent fraction. The aggregates of developing dendritic cells appear at about 1 wk of culture, with 100 or more such clusters being formed per 10(6) blood leukocytes. The aggregates can be dislodged and subcultured as expanding clusters that are covered with cells having the motile sheet-like processes ("veils") of dendritic cells. By about 2 wk, large numbers of single, major histocompatibility complex (MHC) class II-rich dendritic cells begin to be released into the medium. Combined immunoperoxidase and [3H]thymidine autoradiography show that the cells that proliferate within the aggregate lack certain antigenic markers that are found on mature dendritic cells. However, in pulse-chase protocols, the [3H]thymidine-labeled progeny exhibit many typical dendritic cell features, including abundant MHC class II and a cytoplasmic granular antigen identified by monoclonal antibody 2A1. The progeny dendritic cells are potent stimulators of the mixed leukocyte reaction and can home to the T-dependent areas of lymph node after injection into the footpads. We conclude that mouse blood contains GM-CSF-dependent, proliferating progenitors that give rise to large numbers of dendritic cells with characteristic morphology, mobility, phenotype, and strong T cell stimulatory function.

Animals↗
PubMed1992

The immunologic properties of epidermal Langerhans cells as a part of the dendritic cell system.

Dendritic cells form a system of antigen-presenting cells that is widely distributed in the body. They constitute trace populations in lymphoid and non-lymphoid tissues and in the circulation. They are characterized by their typical dendritic and "veiled" morphology, by their constitutive expression of high levels of major histocompatibility complex class II molecules on their surface, and by their outstanding capacity to initiate primary immune responses. Dendritic cells occur in two states of differentiation. In the immature state they are highly specialized for processing foreign protein antigens; in the mature state they efficiently stimulate resting antigen-specific T cells. Dendritic cells can migrate from the non-lymphoid tissues, where they reside in the immature state, via the afferent lymphatics or the blood to the T cell-dependent areas of the lymphoid organs (lymph nodes, spleen). There, they appear as mature dendritic cells. Therefore, dendritic cells are ideally suited to mediate important aspects of immunogenicity: they can acquire antigens in the tissues and process them in an immunogenic form; they can carry the immunogen to the lymphoid organs; and they can find and efficiently activate antigen-specific T cell clones and thus generate an immune response. Studies of epidermal Langerhans cells have greatly helped in establishing this concept. They can be investigated freshly isolated from the epidermis where they represent immature (tissue) dendritic cells. After 2-3 days in culture they develop into mature dendritic cells. The mechanisms of dendritic cell maturation, which can be studied best using epidermal Langerhans cells, and the specific functions of Langerhans cells in immunogenicity are discussed.

Animals↗
PubMed1992

Is the reuse of needles for insulin injection systems associated with a higher risk of cutaneous complications?

Twenty diabetic patients participated in a study to assess if multiple use of needles for insulin injection systems (Pens) is safe under normal daily conditions. The previous mean duration of Pen therapy was 16.3 months. During this time, the 20 patients carried out altogether more than 33,000 injections without any sign of local infection despite needle reuse. Patients were told to use needles if possible for 1, 3, 6, 9, and 12 injections before bacteriological assessment. Bacteriological investigation of these needles showed no contamination, except with one needle used three times, which was colonized with coagulase negative Staphylococcus. In contrast, half of the needles' plastic ground points which touched the skin were contaminated. No signs of infection were observed at the injection sites throughout the study. We conclude that, based on the bacteriostatic effects of commercially formulated insulin and on the siliconisation of needles' surfaces, bacterial growth is sufficiently prevented. Therefore, we can recommend the reuse of pen needles as a simple, safe and cost-beneficial procedure.

Adult↗
PubMed1992

Myocardial perfusion and regression of coronary artery disease in patients on a regimen of intensive physical exercise and low fat diet.

This intervention program tested the applicability and effects of intensive physical exercise and a low fat diet on progression of coronary atherosclerotic lesions and stress-induced myocardial ischemia in patients with stable angina pectoris. Eighteen patients participated in this program for 1 year; they consumed a low fat, low cholesterol diet (less than 20 energy % fat, cholesterol less than 200 mg/day) and exercised for greater than 3 h/week. Change in coronary morphology was assessed by angiography and digital image processing; stress-induced myocardial ischemia was measured by thallium-201 scintigraphy. Results were compared with those in patients receiving "usual care." In the intervention group, significant regression of coronary atherosclerotic lesions was noted in 7 of the 18 patients; no change or progression was present in 11 patients. In patients receiving usual care, regression was detected in only 1, with no change or progression in 11 patients (different from intervention, p less than 0.05). There was a significant reduction in stress-induced myocardial ischemia, which was not limited to patients with regression of coronary atherosclerotic lesions. Thus, regular physical exercise and a low fat diet may retard progression of coronary artery disease; however, improvement of myocardial perfusion may be achieved independently from regression of stenotic lesions.

Angiography, Digital Subtraction↗
PubMed1992

Effective enrichment of murine epidermal Langerhans cells by a modified(mismatched) panning technique.

A method for the enrichment of murine epidermal Langerhans cells (LC) is described in detail. It is based on positive selection of LC from pre-enriched fresh or cultured epidermal cell suspensions derived from ear skin by a modified panning technique. The method uses the interspecies cross-reactivities of anti-immunoglobulin antibodies: when LC in an epidermal cell suspension are labeled with mouse anti-major histocompatibility complex (MHC) class II antibodies they bind to petri dishes coated with anti-rat immunoglobulin antibodies. We therefore call this method "mismatched panning." After rinsing off non-adherent cells, the adherent LC can easily be dislodged by adding excess amounts of rat immunoglobulins, which effectively compete with the LC-bound mouse anti-MHC class II antibodies for binding to the petri dish. Using this modified panning technique, both fresh and cultured LC could be enriched up to more than 90% purity. From one ear, 2.0-3.0 x 10(4) fresh LC and 3.0-4.5 x 10(4) cultured LC could be obtained. Of all LC present in a primary, unenriched epidermal cell suspension, 40-60% were recovered when panned immediately after isolation of the epidermal cells and 50-75% when panned after 3 d of epidermal cell culture. Viability of panned LC was consistently more than 90%. Antigen presenting and T-cell-stimulating capacity of LC and responses to the cytokines granulocyte/macrophage colony-stimulating factor and tumor necrosis factor-alpha were not impaired by this panning procedure. The major advantage of this method compared to pre-existing panning techniques is the ease with which adherent LC can be dislodged from the panning dishes. Because the elution procedure is very gentle, virtually all panned LC are viable. As a consequence, good yields of highly enriched LC can be obtained in a reasonable time.

Animals↗
PubMed1992

Regular physical exercise and low-fat diet. Effects on progression of coronary artery disease.

BACKGROUND: Significant regression of coronary and femoral atherosclerotic lesions has been documented by angiographic studies using aggressive lipid-lowering treatment. This study tested the applicability and effects of intensive physical exercise and low-fat diet on coronary morphology and myocardial perfusion in nonselected patients with stable angina pectoris. METHODS AND RESULTS: Patients were recruited after routine coronary angiography for stable angina pectoris; they were randomized to an intervention group (n = 56) and a control group on "usual care" (n = 57). Treatment comprised intensive physical exercise in group training sessions (minimum, 2 hr/wk), daily home exercise periods (20 min/d), and low-fat, low-cholesterol diet (American Heart Association recommendation, phase 3). No lipid-lowering agents were prescribed. After 12 months of participation, repeat coronary angiography was performed; relative and minimal diameter reductions of coronary lesions were measured by digital image processing. Change in myocardial perfusion was assessed by 201Tl scintigraphy. In patients participating in the intervention group, body weight decreased by 5% (p less than 0.001), total cholesterol by 10% (p less than 0.001), and triglycerides by 24% (p less than 0.001); high density lipoproteins increased by 3% (p = NS). Physical work capacity improved by 23% (p less than 0.0001), and myocardial oxygen consumption, as estimated from maximal rate-pressure product, by 10% (p less than 0.05). Stress-induced myocardial ischemia decreased concurrently, indicating improvement of myocardial perfusion. Based on minimal lesion diameter, progression of coronary lesions was noted in nine patients (23%), no change in 18 patients (45%), and regression in 13 patients (32%). In the control group, metabolic and hemodynamic variables remained essentially unchanged, whereas progression of coronary lesions was noted in 25 patients (48%), no change in 18 patients (35%), and regression in nine patients (17%). These changes were significantly different from the intervention group (p less than 0.05). CONCLUSIONS: In patients participating in regular physical exercise and low-fat diet, coronary artery disease progresses at a slower pace compared with a control group on usual care.

Adult↗
PubMed1992

Prevention of cutaneous melanoma: an epidemiological evaluation of the Swiss campaign.

A national information program, focusing on the main recognized risk factors (primary prevention) and on the potential benefits of early detection (secondary prevention) of cutaneous malignant melanoma, was launched in Switzerland in May 1988. The first campaign, based on a pilot study conducted in 1986 in the canton of Basel, was followed by a recall campaign in July 1989. This report describes the organization of this program and presents an assessment of its initial impact. The number of newly diagnosed cases increased more than twofold (+ 116%) in the two months following the launch of the first campaign (May to June 1988). This trend was accompanied by a statistically significant shift of case distribution towards younger ages (< 60 years; p = 0.003), and a non-significant shift was observed towards less advanced lesions (thickness < or = 1.5 mm). The incidence decreased quickly, though in the twelve month period between the two campaigns it remained 21% higher than before the inception of the program. No appreciable effects were detected from the recall campaign and no difference was seen among regions or between sexes.

Adolescent↗
PubMed1992

[Toxic substances at the work place: do occupational diseases still occur in Switzerland?].

The statistics about work-related diseases influence greatly the setting of prevention priorities. It is consequently of prime importance that these statistics correctly mirror the reality. This paper summarizes the results of studies which show that the real prevalence of work-related diseases is probably two to three times greater than generally admitted; therefore, it seems very important to improve the quality of diagnosis and of data collection.

Humans↗
PubMed1991

Development and optimization of a single-step procedure using protein A affinity chromatography to isolate murine IgG1 monoclonal antibodies from hybridoma supernatants.

Protein A affinity chromatography is a standard method of purifying murine monoclonal antibodies (mabs), primarily because it can be performed easily and achieves high-purity levels. Because of its high concentration capacity, it lends itself particularly well to the isolation of mabs from the supernatants of hybridoma cultures. Unfortunately, murine immunoglobulin (Ig) G1 antibodies, a subclass which occurs frequently in the IgG mabs of mice, binds very poorly to protein A, leading to problems in this isolation procedure. For this reason an attempt was made to increase the effectiveness of protein A affinity chromatography in purifying mabs of this IgG subclass by optimizing the binding conditions. The influence of ionic strength, pH and temperature on the binding capacity of a protein A column was studied. The results show the significance of temperature in the binding of the murine IgG1 mab tested to protein A. Further investigations were carried out to optimize the elution conditions and to study the contamination of mab preparations obtained with non-specific bovine protein A reactive Igs originating from culture medium supplement (10% foetal calf serum). An optimized, automatic single-step procedure to obtain highly purified murine IgG1 mabs from hybridoma culture supernatants was developed.

Animals↗
PubMed1991

[Type III hyperlipoproteinemia in monoclonal IgM gammopathy].

A 42-year-old woman, found to have increased blood-lipid levels, developed hand-line xanthomas 3 months later. She also had an increased erythrocyte-sedimentation rate and a type lambda monoclonal IgM abnormality. In the course of the following 4 years the IgM concentration rose (from 5.8 to 12.3 g/l) steadily and synchronously with those of the triglycerides (from 147 to 391 mg/dl) and cholesterol (from 212 to 380 mg/dl). During the entire period of observation the ratio of VLDL cholesterol and triglyceride concentrations was elevated (greater than 0.4; normal: less than 0.3). Division of the lipoprotein fractions pointed to a type III hyperlipoproteinaemia. She also had an abnormality of lipid metabolism on the basis of a genetic defect (apolipoprotein-E2 homozygotism), which only manifested itself when an additional factor, IgM paraproteinaemia, was present. Paraproteins thus apparently interfered with the breakdown of the lipoproteins. Neither bezafibrate in increasing doses (200-800 mg daily) with low-fat diet nor administration of lovastatin (20 mg twice daily) together with nicotinic acid (500 mg twice daily) were adequate treatment for this form of auto-immune hyperlipidaemia.

Adult↗
PubMed1991

Class II major histocompatibility complex molecules of murine dendritic cells: synthesis, sialylation of invariant chain, and antigen processing capacity are down-regulated upon culture.

Dendritic cells (DCs), such as Langerhans cells (LCs) of the epidermis and the DCs of lymphoid organs such as spleen, are potent antigen presenting cells. DCs express high levels of major histocompatibility complex (MHC) class II molecules, but, partly because of the low numbers of primary DCs in any tissue, there has been no detailed study of the biochemistry of their class II molecules. This information may be needed to help explain recent findings that DCs process native protein antigens when freshly isolated from epidermis and spleen. Processing ceases during culture, yet a strong accessory function for activating resting T cells develops. We studied immunoprecipitates of DC class II and invariant chain (Ii) molecules by two-dimensional gel electrophoresis. We found that (i) freshly isolated LCs synthesize large amounts of class II and Ii polypeptides; (ii) Ii molecules that are known to be involved in antigen processing display an unusually large number of sialic acids in fresh LCs; (iii) with culture, class II and Ii synthesis decreases dramatically and has virtually ceased at 3 days; and (iv) the turnover of class II in pulse/chase experiments is slow, being undetectable over a 12- to 32-hr culture period, whereas the turnover of Ii is rapid. We conclude that MHC class II molecules of DCs do not seem to be qualitatively unique. However, the regulation of class II and Ii expression is distinctive in that biosynthesis proceeds vigorously for a short period of time and the newly synthesized class II remains stably on the cell surface, whereas Ii turns over rapidly. This may enable DCs to process and retain antigens in the peripheral tissues such as skin and migrate to the lymphoid organs to activate T cells there.

Animals↗
PubMed1991

Epidermal Langerhans cells in myelodysplastic syndromes are abnormal.

The myelodysplastic syndromes (MDS) represent clonal disorders of the hematopoietic stem cell that are associated with quantitative and qualitative disturbances of the peripheral blood cells and a high risk for the transition to overt leukemia. As epidermal Langerhans cells (LC) are bone-marrow-derived cells, we were interested to see whether they are altered in patients with MDS. Epidermal sheets were prepared from biopsies taken from the thighs of nine patients with MDS and five control persons and processed for immunoperoxidase staining of CD1a antigens. The density and morphology of CD1a+ cells (i.e., LC) was evaluated by visual assessment as well as automatic image analysis. The density of LC was reduced in seven of nine patients (range, 30-75% of normal), whereas the morphology of LC appeared to be altered in all MDS patients in that the LC displayed large and bizarre cell bodies with only a few and often abnormally long dendrites. The HLA-DR expression by LC was not altered, as shown by double immunofluorescence staining of CD1a and HLA-DR antigens. Ultrastructurally, LC again appeared enlarged and often presented with bizarre nuclei, yet displayed no other abnormalities. Our findings suggest that LC are abnormal in MDS and might even indicate a more wide-spread involvement of the dendritic cell lineage in this syndrome.

Humans↗
PubMed1991

Treatment of coronary heart disease with diet and exercise--problems of compliance.

The effects of low fat diet and intensive physical exercise were examined in a randomized prospective study in patients with angiographically documented coronary heart disease. In addition to supervised regular physical exercise, patients of the intervention group (n = 18) were subjected to intensive dietary counselling with the aim of a low fat, low cholesterol diet to be maintained for at least 12 months. The control group (n = 27) received relevant advise only and usual care by private physicians. In the intervention group there was significant lowering of plasma triglycerides (202 +/- 82/141 +/- 74 mg/dl) and body weight (78.2 +/- 9.5/73.7 +/- 10.4 kg) while total and LDL cholesterol did not change significantly. There was a tendency for a rise of HDL-cholesterol (35.6 +/- 9.0/40.4 +/- 14.8 mg/dl, p = 0.07). According to 24-hour diet protocols there was a significant lowering of energy intake (2.298 +/- 697/1.602 +/- 758 kcal/day), of fat intake (111.7 +/- 44.4/52.0 +/- 23.9 g/day) and of intake of dietary cholesterol (402.8 +/- 186/161.3 +/- 100.3 mg/day) as well as of saturated fatty acids (42.5 +/- 20.4/14.3 +/- 8.1 g/day). Fatty acid composition of adipose tissue was not correlated with the patients' 24-hour dietary protocols. In the control group there were no changes of plasma lipids, body weight or diet composition according to 24-hour protocols after 1 year compared to data at the beginning of the study. There was, however, a marked correlation of adipose tissue composition and dietary information given by the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1991

[Modification of risk factors through physical training and low-fat diet].

This intervention program investigated the applicability and the effects of intensive physical exercise and low-fat diet on the progression of coronary atherosclerotic lesions and stress induced myocardial ischemia in patients with stable angina pectoris. Patients participating in this study were recruited following routine coronary angiography for angina pectoris. Inclusion criteria were male sex, stable symptoms, a willingness to participate in the study for at least twelve months, and coronary artery stenoses well documented by angiography. Exclusion criteria were unstable angina pectoris, left main coronary artery stenosis greater than 25% luminal diameter reduction, severely depressed left ventricular ejection fraction (less than 35%), significant valvular heart disease, insulin-dependent diabetes mellitus, primary hypercholesterolemia (type II hyperlipoproteinemia, low-density lipoprotein greater than 210 mg/dl), and conditions precluding regular physical exercise. 18 patients participated in this program for one year; they consumed a low-fat, low-cholesterol diet (less than 20 energy % fat, cholesterol less than 200 mg/day) and exercised for more than 3 h/week. Myocardial oxygen consumption was estimated from maximum rate-pressure product at peak exercise; it was correlated to stress induced myocardial ischemia, as measured by 201Tl-scintigraphy. Results were compared with those of 18 matched patients on "usual care". In the intervention group, physical work capacity (161 +/- 34 W vs. 194 +/- 42 W) and maximum rate pressure product (25.0 +/- 6.3 x 10(3) vs. 27.2 +/- 5.3 x 10(3)) increased significantly (p less than 0.01). Patients willing to devote time and effort to intensive physical exercise and to comply with a low-fat diet may benefit from this form of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Disease↗
PubMed1991

[Different rates of progression of heart valve defects].

In order to determine the rate of progression in valvular heart disease, the records of patients with simple valve lesions and two cardiac catheterizations performed prior to surgery were examined retrospectively. In 53 patients (mitral regurgitation n = 16, aortic regurgitation n = 13, mitral stenosis n = 13, aortic stenosis n = 11) complete data were available. The time interval between the two studies averaged 47 +/- 24 months. In patients with mitral regurgitation left ventricular ejection fraction deteriorated significantly faster than in the other groups; the rate of left ventricular volume gain and rise in pulmonary pressure also tended to be higher in this group. The transvalvular gradient in aortic stenosis showed a highly significant increase during the observation period (56 +/- 26 mm Hg vs 78 +/- 29 mm Hg; p less than 0.01), however, left ventricular ejection fraction remained within normal limits. These data indicate that patients with mitral regurgitation should be followed closely prior to valve replacement.

Adult↗
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↗