Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 289 records · Page 16Linked to original sources

PubMed1994

Limited Stage Small Cell Lung Cancer: Current Treatment and Clinical Trials.

Progress in the treatment of patients with small cell lung cancer (SCLC), which seemed so rapid a decade ago, appears to have slowed. This has led to frustration and discouragement. Some of this pessimism is based on premature optimism in the past, but much stems from the realization that over 90% of patients with limited stage SCLC still die of the disease. Such aggregate judgments obscure the facts that major advances have been made in understanding the biologic basis of this disease and that modest but clinically valuable progress has been made in therapy. In view of the large number of patients diagnosed with SCLC each year, relatively small improvement in long-term outcomes can result in the survival of many patients each year. This article reviews the current status of care for patients with limited stage SCLC and discusses directions for clinical research in the 1990s.

Journal Article↗

PubMed1994

[Local immunomodulation in atopic and nonatopic children with nonspecific respiratory tract diseases].

The authors report their own results of local immunomodulation with IRS 19 in 57 atopic and nonatopic children having nonspecific chronical diseases of the respiratory tract. The results were obtained on the basis of complex diagnostical procedures before and after local immunomodulation. These results are demonstrated by tables, figures and graphs. By comparing the results obtained with local immunomodulation, it was found that prophylactic and therapeutic efficiency of IRS 19 is better in nonatopic children than in atopic ones. The detailed analyses showed that the local immunomodulation caused not only an increased concentration of the immunoglobulins IgG, IgM, IgA but also of the IgE.

Adjuvants, Immunologic↗

PubMed1994

Forms of physiological aliasing within the heart rate fluctuations by higher frequent respiratory movements.

In adult conscious rabbits, the respiratory frequency (RF) is almost always higher than half the heart rate (HR) Thus, no "classical" respiratory sinus arrhythmia occurred. But now, slow HR fluctuations, which were not synchronous to the respiratory rhythm but effected by it, occurred systematically. By cholinergic blockade, these slow HR fluctuations could be essentially reduced but not completely abolished. Up to now, this phenomenon was not be taken into account in the analysis of HR fluctuations. Thus misinterpretations are inevitable. During general anaesthesia, the RF decrease up to 2 RF < HR, and now classical respiratory sinus arrhythmia occurred which also could be essentially reduced but not completely abolished by vagal blockade. The possibilities of calculation of such slow HR fluctuations were shown, as those during 1/2 HR < RF < 3/2 HR and RF > 3/2 HR.

Acid-Base Equilibrium↗

PubMed1994

Superantigen-induced anergy of V beta 8+ CD4+ T cells induces functional but non-proliferative T cells in vivo.

The response profile of staphylococcal enterotoxin B (SEB)-primed murine V beta 8+ CD4+ and V beta 8+ CD8+ T cells was analysed upon rechallenge in vitro. While in vitro responses to secondary stimulation with SEB were reduced to background levels, the in vivo reactivity after rechallenge with SEB was retained, in that SEB-primed mice succumbed to lethal T-cell shock, lymphokines [interleukin-1 (IL-1), IL-2, Il-4, IL-6, IL-10, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha)], and lymphokine-specific mRNA accumulation could be detected in V beta 8+ CD4+ and V beta 8+ CD8+ T cells. However, V beta 8+ CD4+ T cells failed to enter the cell cycle. While the phenotype of V beta 8+ CD8+ T cells was indistinguishable from that of their counterparts from naive mice, V beta 8+ CD4+ T cells exhibited in vivo an unusual phenotype as non-proliferative but functional T cells. We conclude that in vitro-defined anergy does not disclose the functional abilities of ligand-reactive V beta 8+ T cells in vivo, and that priming with superantigen (SAg) induces in vivo a differentiation of SEB-reactive V beta 8+ CD4+ T cells into a non-proliferative but functional phenotype.

Animals↗

PubMed1994

Jaffe-Campanacci syndrome: case report and review of literature.

We report a 27-year-old Caucasian woman with Jaffe-Campanacci syndrome. She presented with multiple café-au-lait spots and multiple non-ossifying fibromata of the bones, noted on radiographs and proven by tissue biopsies. Only the left side was involved. She also suffered from moderate scoliosis, stenosis of the aortic isthmus, chylothorax, and a chylopericardium. The etiology is discussed.

Adult↗

PubMed1994

Randomized phase 2 evaluation of preoperative radiation therapy and preoperative chemotherapy with mitomycin, vinblastine, and cisplatin in patients with technically unresectable stage IIIA and IIIB non-small cell cancer of the lung. LCSG 881.

Between June 1988 and January 1980, 67 patients with pathologic stage III non-small cell lung cancer were randomized to receive either preoperative mitomycin, vinblastine, and cisplatin (MVP) chemotherapy (cisplatin 120 mg/m2, and mitomycin, 8 mg/m2 day 1 + 29, and vinblastine, 4.5 mg/m2 on day 1, 15, 22, and 29 and 2.0 mg/m2 day 8), or preoperative radiotherapy (44 Gy in 22 fractions to the primary tumor and mediastinum). The purpose of this study was to identify a treatment approach that showed sufficient effectiveness and acceptable toxicity to warrant testing by prospective randomized trial against "standard" nonsurgical treatment. All patients had surgical staging of the mediastinum and had either unresectable N2 disease or T4 disease with proximal extension of disease along the pulmonary artery. Response to preoperative therapy was evaluated 8 weeks after beginning treatment and patients with complete or partial radiographic response were to undergo surgical exploration and resection if possible. Fifty-seven patients were eligible and evaluable for response. Of the 67 total patients, 3 were unavailable for follow-up, 4 were ineligible, 1 was canceled, and 2 refused all treatment after having been randomized. Of the eligible and evaluable patients, 49 had stage IIIA and 8 had stage IIIB disease. Randomization was to MVP in 26 cases and to radiotherapy (XRT) in 31. Radiographic response to treatment was virtually identical for the two approaches, with 29 of the 57 evaluable patients achieving objective responses. In patients achieving radiographic response, 24 underwent surgical exploration and 20 underwent resection, of which 18 were complete. The mediastinum was free of tumor in seven patients but only two pathologic complete responses were seen (one each to XRT and MVP). In addition, ten nonresponders underwent surgery; seven underwent resection. Median survival for the entire group is 12 months, with a 27% actuarial survival at 4 years. Two patients died of treatment toxicity during preoperative therapy. Overall toxicity included 2 preoperative toxic deaths and 6 postoperative deaths in 34 patients who underwent surgical exploration (3 each with XRT and MVP) due to adult respiratory distress syndrome (3), myocardial infarction (1), pulmonary edema (1), and esophageal fistula (1), for an overall death rate 8 of 57 (14%) and a perioperative death rate in surgically explored patients of 6/34 (18%). These preoperative regimens, in the population studied herein, were of modest efficacy and substantial toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Proliferative and cytolytic responses of human gamma delta T cells display a distinct specificity pattern.

The function and physiological role of gamma delta T cells are still unknown. Concerning the specificity of these cells, a proliferative response towards microbial ligands has been noted, whereas in terms of effector functions in humans a cytolytic activity against a variety of tumour targets is most prominent. Here we show data demonstrating that the cytolytic activity of activated human gamma delta T cells does not reflect the specificity of these cells in primary in vitro stimulation; moreover, we provide evidence that the recognition of target cells by gamma delta T cells can have different qualities. gamma delta T cells proliferate vigorously in primary in vitro reaction upon stimulation with various B-cell tumour lines but not with the T-cell lines Jurkat or Molt-4. However, gamma delta T cells stimulated primarily with phytohaemagglutinin or with cells from B-cell lines gain unrestricted cytolytic activity against a broad set of tumour targets, including Jurkat and Molt-4; the same set of targets is capable of inducing release of serine esterases (SE) from gamma delta T-effector cells. Whereas the cytolytic activity in the 51Cr-assay against the B-cell lines and against Molt-4 depends on the presence of Ca2+ ions in the assay, the lysis of Jurkat cells is only slightly reduced upon removal of Ca2+ from the medium; the SE release, however, is Ca2+ dependent in all cases. Taken together, these data suggest several different ways of target cell recognition by gamma delta T cells leading to either proliferation or triggering of cytolytic activity, and argue against an involvement of the gamma delta T-cell receptor in the cytotoxic activity of gamma delta T cells.

Calcium↗

PubMed1994

Constituents of euphorbiaceae 12. Comm. (1). Isolation and structure elucidation of four new cerebrosides from Euphorbia biglandulosa Desf.

Four new cerebrosides 4-6 were isolated from the latex of Euphorbia biglandulosa Desf. and their structures determined. Normal and reverse-phase flash chromatography was effective for the isolation of the cerebrosides, and FAB-MS spectrometry, 1H-NMR, 13C-NMR, DQF-COSY and HMQC experiments and chemical reactions were useful in elucidating their structure. EI-MS of the dimethyl disulfide derivatives of the long chain bases and glucosphingoside-heptaacetates was decisive for the determination of the double bond position on the long chain parts.

Cerebrosides↗

PubMed1994

Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation.

Interleukin-8 (IL-8) is a potent cytokine for recruitment and activation of neutrophils. To visualize its distribution in the intestinal mucosa and to understand better its possible role in the induction and promotion of inflammatory bowel disease, expression of the IL-8 gene was analyzed in resected bowel segments of 14 patients with active Crohn's disease or ulcerative colitis. In situ hybridization with IL-8 anti-sense RNA probes revealed strong and specific signals in the histologically affected mucosa. The number of cells expressing IL-8 gene correlated with the histological grade of active inflammation. In accordance with the characteristic histological signs of active disease, IL-8-expressing cells were diffusely distributed over the entire affected mucosa in patients with ulcerative colitis, whereas in patients with Crohn's disease, IL-8-expressing cells showed a focal distribution pattern. Cells expressing IL-8 were mainly located at the base of ulcers, in inflammatory exudates on mucosal surfaces, in crypt abscesses, and at the border of fistulae. Analysis of semi-serial sections pointed to macrophages, neutrophils, and epithelial cells as possible sources of this cytokine in active inflammatory bowel disease. We consistently failed to detect IL-8 messenger RNA in the mucosa of uninvolved bowel segments and in normal-appearing control mucosa of patients with colon cancer. In contrast, tissue specimens from two patients with acute appendicitis displayed IL-8-expressing cells in the mucosa. These results support the notion that IL-8 plays and important but nonspecific role in the pathogenesis of inflammatory bowel disease and that the production of IL-8 messenger RNA is restricted to areas with histological signs of inflammatory activity and mucosal destruction.

Adult↗

PubMed1994

[Problems in auditory perception and verbal and nonverbal intelligence].

The connection between auditory perception and verbal/nonverbal cognitive achievements were studied in a sample of 300 clients of the school counselling service in the district of Neuss. Nearly 46% of the pupils do have problems with the auditory perception; these pupils do have lower test-results in overall intelligence, especially in verbal cognitive achievements. It is concluded that tests concerning the auditory perception should be used more often.

Adolescent↗

PubMed1993

Bacterial superantigens induce rapid and T cell receptor V beta-selective down-regulation of L-selectin (gp90Mel-14) in vivo.

Upon challenge of mice with bacterial superantigens such as staphylococcal enterotoxin B, several facets of TCR V beta-selective acute T-cell alterations can be observed, which include acute T cell priming, and systemic lymphokine release followed by ligand-specific unresponsiveness. Prompted by experiments showing that stimulation of T cells by phorbol esters in vitro results in rapid shedding of the L-selectin homing receptor, we investigated the expression of adhesion molecules on superantigen-responsive T cells in vivo. Here we show that bacterial superantigens cause TCR V beta-specific loss of L-selectin. Down-regulation of L-selectin was selective, since the expression of other lymphocyte surface receptors was not changed. L-Selectin down-regulation represents a superantigen-induced immediate cell surface alteration and was not observed on T cells stimulated by TCR-specific antibodies. Loss of expression was almost complete within 30 min, and recovered 50 h after challenge. The results suggest that acute loss of L-selectin is a hallmark of T cell activation by bacterial superantigens that may result in profound changes of T lymphocyte recirculation pathways.

Animals↗

PubMed1993

Disparity-sensitive cells in the owl have a characteristic disparity.

We experience the visual world as being three-dimensional. A major source of depth information derives from the slightly different views of each eye, leading to small variations in the retinal images ('disparities'). Neurons sensitive to visual disparities are thought to form the neural basis of stereo vision. Barn owls as well as several mammalian species have neurons that are sensitive to visual disparities. But how visual disparities are represented in the brain has been a matter of discussion ever since the first disparity-sensitive neurons were found some 25 years ago. Here we adopt a new approach to this problem and study the neural computation of visual disparities with a paradigm borrowed from auditory research. The measurement of interaural time difference (ITD) has many similarities with the measurement of visual disparity on the formal, algorithmic level. We speculate that the similarities might extend to the level of neural computation. The neural representation of ITD is well understood, and we have studied the representation of disparities with visual stimuli analogous to those successfully used in acoustic experiments. For example, ITD is converted in the brain to a pathlength on an axon that, owing to the finite conduction velocity in neurons, exactly matches the external ITD. This pathlength is called 'characteristic delay'. Our results suggest that there is an analogue of the characteristic delay in stereo vision which we propose to call 'characteristic disparity'.

Animals↗

PubMed1993

Endogenous superantigen expression controlled by a novel promoter in the MMTV long terminal repeat.

Endogenous superantigens are encoded by the open reading frame contained within the mouse mammary tumour virus long terminal repeat (MMTV LTR). Superantigen expression results in T-cell proliferation and, during early ontogeny, T-cell deletion. Here we identify a novel promoter located upstream of the previously described MMTV promoter. Transcripts from this promoter initiate within the U3 region of the MMTV LTR and splice to the acceptor for endogenous superantigen coding region. The novel U3 promoter is active in B lymphocytes, which are cognate antigen-presenting cells for endogenous superantigen, and is able to direct expression of superantigen in the absence of the previously described MMTV promoter.

Animals↗

PubMed1993

Acquired resistance to superantigen-induced T cell shock. V beta selective T cell unresponsiveness unfolds directly from a transient state of hyperreactivity.

TCR V beta selective T cell activation and systemic release of T cell-derived lymphokines causing lethal shock in D-galactosamine (D-Gal)-sensitized mice depicts only one facet of in vivo challenge with the superantigen staphylococcal enterotoxin B (SEB). An immediate second major aspect represents the induction of peripheral unresponsiveness in SEB-reactive V beta 8+ T cells. SEB causes in vivo within 4 h resistance to an otherwise lethal challenge with SEB plus D-Gal, as well as to a challenge with the heterologous ligand toxic shock syndrome toxin 1 plus D-Gal. Contrary to the first challenge, no serum-borne IL-2 and TNF are discernible during the second challenge. On the other hand, kinetic analyses in vitro of LN cells draining the site of the first in vivo challenge indicate that SEB-reactive T cells develop via a transient state of hyperreactivity into a profound state of ligand-specific unresponsiveness. Yet unresponsive V beta 8+ T cells express IL-2R and are responsive to the growth-promoting effect of IL-2. Cyclosporin A does not impair sequential induction of hyperreactivity and unresponsiveness with concomitant IL-2R expression, but effectively blocks systemic IL-2 and TNF release during the initial hyperreactive phase. Taken together, the in vitro data imply that ligand-specific hyperreactivity followed immediately by ligand-specific unresponsiveness represents a hallmark of in vivo challenge with the superantigen SEB. The in vivo data suggest the existence of additional suppressive elements masking the ligand specificity of the state of unresponsiveness induced by SEB.

Animals↗

PubMed1993

Primary in vivo responses to ovalbumin. Probing the predictive value of the Kb binding motif.

CD8+ cytolytic T cells recognize Ag presented by MHC class I molecules on the surface of target cells. It is known that presenting cells process nascent protein into peptides of approximately eight to nine amino acids which bind to the peptide groove of MHC class I and are transported to the cell surface. Recently, several laboratories have postulated that each MHC class I haplotype has a binding motif of at least two amino acids nested within the peptide. One such motif is XXXXF/YXXL which binds to the mouse MHC class I molecule, H2-Kb, and can be found in the known antigenic peptide from OVA at amino acids 257-264. By using the motif to scan OVA five peptides were found that fit this pattern, OVA 11-18, OVA 55-62, OVA 107-114, OVA 176-183, and OVA 257-264. Binding studies revealed that three out of the five peptides (OVA 55-62, OVA 176-183, and OVA 257-264) bind to MHC class I. To test the natural antigenicity of the predicted peptides, C57BL/6 mice were immunized with OVA containing immunostimulating complexes to elicit a MHC class I-driven response to naturally processed OVA. The cytolytic potential of the responding T cell population was tested in vitro by using EL-4 cells preincubated with the predicted synthetic peptides as targets. The known antigenic peptide OVA 257-264 elicited a strong response; however, OVA 176-183 was also recognized while the remaining three were not recognized. The CTL response did not strictly correlate with the ability of the selected peptides to bind Kb, for example, OVA 55-62 was able to bind Kb efficiently, yet elicited no cytolytic response. In addition, the plasticity of the peptide-binding motif was probed by making amino acid substitutions, and as a result the motif proved to be more flexible than previously suspected. This represents the first report of a Kb-associated CTL epitope within OVA other than OVA 257-264. It also demonstrates the predictive quality of the Kb-binding motif; however, not all predicted peptides were recognized by primary OVA-induced CTL, implying more rules of processing and binding are needed.

Amino Acid Sequence↗

PubMed1993

Quantitative analysis of lymphokine mRNA expression by a nonradioactive method using PCR and anion exchange chromatography.

Amplification of DNA by the polymerase chain reaction (PCR) has become an efficient tool in the study of gene expression. We describe the use of HPLC anion exchange chromatography to quantitate PCR products amplified from cDNA. The technique circumvents the use of both radioactivity and gel electrophoresis. We show that the method permits accurate quantitation of the gene product of interest and provides a clear separation of specific and non-specific products. The technique was applied to quantitate TNF-beta mRNA levels in unstimulated and stimulated mouse T cells.

Animals↗

PubMed1993

Clonal deletion as direct consequence of an in vivo T cell response to bacterial superantigen.

To date clonal deletion of peripheral mature T cells is restricted to in vivo model systems characterized by prolonged exposure of mice to antigens and clonal T cell expansion preceding clonal deletion. Here we describe that upon challenge of mice with the superantigen staphylococcal enterotoxin B two immediate events become imposed on ligand-reactive V beta 8+ T cells in lymph node cells draining the local site of injection. First, and within hours V beta selective clonal deletion is initiated via an apoptotic process. Second, the remaining V beta 8+ T cells first develop a profound state of ligand-specific unresponsiveness and subsequently initiate clonal in vivo growth. It is suggested that the dichotomy of events observed reflects a direct consequence of T cell receptor occupancy in the context of inappropriate signalling.

Animals↗

PubMed1993

Pathogenesis of the toxic shock syndrome: T cell mediated lethal shock caused by the superantigen TSST-1.

The pathogenesis of the toxic shock syndrome (TSS) is only incompletely understood. We now present evidence that TSS toxin-1 (TSST-1), one of the superantigens produced by Staphylococcus aureus, induces lethal shock in D-galactosamine sensitized mice. In this model TSS is dependent on T cells, since cyclosporin A (CsA) completely blocked development of shock, and since T cell-deficient SCID mice did not show signs of disease upon injection with TSST-1. However, SCID mice repopulated with T cells succumbed to lethal shock. The disease is characterized by a burst of lymphokines like interleukin-2 (IL-2) and tumor necrosis factor (TNF) released into the sera of TSST-1-treated animals. Already 1-2 h after TSST-1 application TNF serum levels peaked and IL-2 levels peaked around 4 h after treatment. TNF appears as key mediator of TSS, because anti-TNF monoclonal antibodies protected TSST-1-challenged mice. Interestingly, the burst of TNF in serum was noted well in advance of detectable markers of T cell activation. Thus, about 5% of all peripheral T cells started to express the IL-2 receptors as late as 4 h after treatment. Comparing TSST-1- and endotoxin-induced shock we conclude that TNF effects shock in both diseases. However, the type of cells involved appears distinct in that T cells cause TSS triggered by the exotosin TSST-1 while macrophages mediate the shock induced by endotoxins.

Animals↗