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Biomedical subjects

K M Müller

Publications and source records attributed to K M Müller.

At least 217 records · Page 12Linked to original sources

[The content of asbestos bodies in the bronchoalveolar fluid as a parameter of an increased pulmonary asbestos load].

Pulmonary asbestos burdens are usually determined by quantitative pulmonary dust analysis. The aim of this study was to investigate the value of bronchoalveolar lavage (BAL) for this purpose. First, the upper limit of normal for asbestos bodies (AB) in BAL fluid was established using a reference group of 371 patients with no evidence of increased exposure to asbestos. 99% of these patients had less than 0.5 AB/ml. In order to see whether BAL fluid AB concentration reflected pulmonary tissue content, BAL fluid and lung tissue from a further 64 patients with diverse histories of asbestos exposure were investigated. There was a positive association between AB concentration in BAL fluid and lung tissue only for the overall group of 64 patients (r = 0.86; P < 0.001). Twelve of 13 patients with more than 1 AB/ml and ten patients with more than 5 AB/ml had more than 1000 AB/cm3 lung tissue, a value that is usually exceeded in asbestosis. When the upper concentration limit was set at 0.5 AB/ml for BAL fluid and 50 AB/cm3 for lung tissue, only two out of 64 patients had a false positive value (specificity 95%), but eleven patients had false negative results (sensitivity 58%). These investigations establish that concentrations of > or = 0.5 AB/ml are a reliable indicator of increased asbestos exposure and concentrations > 1 AB/ml are associated with a higher probability of having more than 1000 AB/cm3 lung tissue. However, exclusion of increased asbestos exposure is not possible on the basis of negative BAL findings, since the sensitivity of the method is too low.

Adult↗

Th2 cells mediate IL-4-dependent local tissue inflammation.

We investigated whether polyclonal murine Th1 and Th2 cells obtained after short term culture in vitro were capable of mediating tissue inflammation in vivo. Th cells were pulsed with mAb to the TCR/CD3 complex and injected into the footpads or ears of naive syngeneic recipient mice. Th1 induced delayed swelling that peaked at 24 to 48 h and lasted > or = 5 days. Th2-induced swelling peaked at 6 h and lasted < or = 48 h. Similar responses were also observed in athymic nude mice. Lesions with both Th1 and Th2 cells contained a predominant neutrophilic infiltrate at 6 h, and mainly mononuclear cells at 48 h. The inflammatory response with Th2 was blocked by cyclosporin A, by mAb to IL-4 or by soluble rIL-4R. The requirement for IL-4 was early and transient. Four alloreactive short term Th2 clones induced swelling in allogeneic recipients. mAb- and IL-4-dependent swelling responses were also observed with two long term Th2 clones. Our results demonstrate that Th2 cells mediate IL-4-dependent tissue inflammation, and strengthen the concept that Th2 cells play an important role in some T cell-dependent immune reactions and, possibly, in allergic disorders such as atopic dermatitis and allergic asthma.

Animals↗

Lymphokine profiles in contact sensitivity induced by dinitrofluorobenzene and tolerance induced by dinitrothiocyanobenzene.

We determined the lymphokines involved in the immune response to epicutaneously applied dinitrofluorobenzene (DNFB), a sensitizer, and dinitrothiocyanobenzene (DNTB), a tolerogen. Hapten-dependent T-cell proliferation and production of interleukin-2, interleukin-3 and interleukin-4 by lymph node cells (LNC) in mice painted with these cross-reactive haptens were measured by specific lymphokine assays. Proliferation of LNC in tolerized animals was lower than in sensitized mice. LNC from DNTB-treated mice produced lower amounts of interleukin-2, interleukin-3 and interleukin-4 than cells from DNFB-painted mice. These results may explain hapten-specific tolerance induced by DNTB which results in deficient production of both type 1 T-helper cell (Th1) and type 2 T-helper cell (Th2) lymphokines in response to hapten re-exposure. Deficient interleukin-4 production by cells from tolerized mice was corrected by the addition of exogenous interleukin-2. The suppressor function of adoptively transferred T cells from animals tolerized with dinitrothiocyanobenzene may be related to a shift in the balance of Th1 and Th2 lymphokines in favour of the latter, since recipient T cells might provide the source of interleukin-2 that induces interleukin-4 production by donor T cells.

Animals↗

Role of calcitonin gene-related peptide and nitric oxide in the gastroprotective effect of capsaicin in the rat.

BACKGROUND: Capsaicin-sensitive neurons contain various peptides including calcitonin gene-related peptide. This study examines (1) whether calcitonin gene-related peptide is involved in capsaicin-induced gastroprotection and (2) whether nitric oxide and prostaglandin are required for calcitonin gene-related peptide to prevent mucosal injury. METHODS: Gastroprotection by capsaicin or calcitonin gene-related peptide against ethanol-induced gross and histological damage was studied after pretreatment with the calcitonin gene-related peptide receptor antagonist, human calcitonin gene-related peptide8-37, anti-calcitonin gene-related peptide antibodies, and NG-nitro-L-arginine. RESULTS: Protection by capsaicin was dose-dependently (50% inhibitory dose, 305 pmol.kg-1.min-1) antagonized by human calcitonin gene-related peptide8-37 and significantly attenuated by anti-calcitonin gene-related peptide antibodies. NG-nitro-L-arginine dose-dependently inhibited the protective effect of calcitonin gene-related peptide (50% inhibitory dose, 0.9 mg/kg), 3 mg/kg completely blocking protection. L-Arginine reversed the effects of NG-nitro-L-arginine. Protection by calcitonin gene-related peptide was neither associated with increased prostaglandin formation nor inhibited by indomethacin. CONCLUSIONS: The results suggest that calcitonin gene-related peptide is an essential mediator of the protection elicited by stimulation of capsaicin-sensitive neurons and that the protective effect of calcitonin gene-related peptide is lost after blockade of the nitric oxide system but not the prostaglandin system.

Animals↗

Cytoimmunological abnormalities in cerebrospinal fluid in early stages of HIV-1 infection often precede changes in blood.

We determined the proportions of CD2+, CD4+ and CD8+ lymphocytes in the cerebrospinal fluid (CSF) and paired blood samples of 19 neurologically examined subjects with CDC II/III stage HIV-1 infection and 21 controls. Using a three-layer indirect immunoperoxidase technique, we found that 16 HIV-1-infected subjects had an abnormally low CD4+/CD8+ ratio of the CSF due to a decrease in the proportion of CD4+ T cells and/or an increase in that of CD8+ lymphocytes. Compared to controls, in the HIV-1-infected group this ratio appeared to be lower in both CSF and blood (P < 0.001). The changes of lymphocyte subpopulations were more marked in the CSF than in blood, and no clear associations were found between the findings of paired CSF and blood samples. Cytological examination of the CSF revealed that 12 of 14 patients had an elevated total cell count and an abnormal differential count with a predominance of mononuclear phagocytes. An elevated number and/or proportion of enlarged lymphoid cells was found in most cases. The total cell counts, and total numbers of mononuclear phagocytes and lymphocytes of the patients were higher than in controls (P < 0.001). Our study shows that the changes in CSF lymphocyte subsets often precede those in blood and that immunological events in the central nervous system (CNS) are not directly reflected in peripheral blood. Cytoimmunological abnormalities in the CSF of individuals with early stages of HIV-1 infection indicate subclinical CNS involvement, and may be of importance for therapeutic considerations.

Acquired Immunodeficiency Syndrome↗

[Crigler-Najjar syndrome type II in a 17-year-old girl].

The Crigler-Najjar-Syndrome type II is characterised by the decreased activity of the bilirubin-UDP-glucuronyltransferase. This fact leads to an increase of the indirect bilirubin to 6-10 mg/dl. The mode of hereditary transmission is autosomal dominant with variable penetrance. The age of manifestation varies from the first year to the second decade of life. The Crigler-Najjar-Syndrome type II of a 17-year-old girl is reported. The diagnosis was made on the basis of the pattern of laboratory parameters in combination with an uneventful morphology of the liver. Under treatment with Chlofibrat the decrease of the serum total bilirubin from 10.4 mg/dl to 2 mg/dl was achieved.

Adolescent↗

[Anti-human collagenase type IV expression in preneoplastic lesions and early squamous cell lung carcinoma].

Proteolytic enzymes like collagenase type IV are relevant to the destruction of matrix-components within the scope of invasive tumor growth. Preneoplastic lesions of the bronchial mucosa and early squamous cell carcinomas were investigated immunohistochemically using anti-human-collagenase type IV monoclonal antibodies due to the question of enzymatic proteolysis of basement membrane structures. With increasing malignant epithelial transformation an increase of collagenase type IV expression was observed in single atypical cells of severe dysplasia, carcinoma in situ and early cancer of the bronchus. Collagenase type IV expression can be evaluated as enhanced proteolytic potency for degradation of matrix structures of the basement membrane as one factor for early infiltration in preneoplastic lesions up to early squamous cell carcinomas of the lung.

Antibodies, Monoclonal↗

[Pulmonary and pleural reaction patterns to artificial mineral fibers --rockwool].

Epidemiological and animal studies about the fibrogenic and carcinogenic properties of natural mineral fibers required the development of man made vitreous fibers as substitutes for asbestos containing material. The question about the possible fibrogenic and carcinogenic properties of man-made vitreous fibers is not yet answered. By means of different experimental animal studies we tried to investigate the man made vitreous fibers-related pulmonary and pleural diseases. The experimental administration of rockwool induce lesions in the lung of the rats. The lung showed an extensive granulomatous inflammation. In the observation time of 10 months we did not find any malignant tumor of the lung and the pleura.

Animals↗

[Thoracic bilateral myelolipoma].

Diagnostics, histogenetic derivatives and determination of the mediastinal neoplasms can still be problematic today despite the use of CT and MRT. Although the exact location and determination of neoplasmic density help to reduce the differential diagnostic spectrum in some cases, in the case of a 50-year old patient it was only via thoracoscopy and the taking of specimens that the diagnosis of a bilateral paravertebral crescent-shaped tumour of the posterior mediastinum as a rare myelolipoma could be obtained. Formal and causal pathogenesis of myelopomas are referred to in this paper with special reference to the clinical and pathologico-anatomical findings.

Biopsy↗

[Clinical aspects, morphology and therapy of an unusual case of bilateral macrodactyly].

Macrodactyly, originally described by von Klein in 1824, is one of the rarest congenital anomalies of the hand. It displays a wide variety of manifestations, and its association with other congenital defects and syndromes has been discussed by many authors. A rare case involving an adult with bilateral, hyperostotic macrodactyly of the hands is presented. The hands were not treated in childhood. Clinical findings, pathology, and treatment are discussed.

Adult↗

New aspects in the staging of lung cancer. Prospective validation of the International Union Against Cancer TNM classification.

BACKGROUND AND METHODS: To validate the new TNM definitions for lung cancer (International Union Against Cancer [UICC] TNM classification, 4th edition, 1987), the data of 3823 patients were analyzed prospectively in terms of concordance between clinical (TNM) and pathologically confirmed classification (pTNM), the value of the various diagnostic techniques in estimating the pathologically confirmed classification, and the prognostic relevance of the new TNM definitions. RESULTS: With regard to the primary tumor (T), clinical and pathologic classifications were identical in 63%; with regard to lymph node involvement (N), the agreement was 47%; for distant metastasis agreement occurred in 91% of cases and for the stages it occurred in 56%. As to the primary tumor (T), the accuracy of radiography (59%) was nearly identical to that of computed tomography (CT) (58%). Both techniques were less precise in determining the extent of lymph node involvement (CT, correct assessments in 50%; radiography, correct assessments in 43%). The statistically significant differences in the prognosis for the T, N, and M categories and for the stages and the categories of the new R classification could be confirmed. Allowance should be made for the different prognosis between T1N0M0 and T2N0M0 by the new Substages IA and Ib of Stage I. CONCLUSIONS: By the new TNM definitions for bronchus carcinoma, international conformity became feasible and practical, and the improvement of its prognostic relevance provided a more reliable basis for establishing guidelines for individual oncologic concepts.

Bronchial Neoplasms↗

Central role for TCR/CD3 ligation in the differentiation of CD4+ T cells toward A Th1 or Th2 functional phenotype.

Activated CD4+ T cells can be classified into distinct subsets; the most divergent among them may be considered to be the IL-2 and IFN-gamma-producing Th1 clones and the IL-4 and IL-5-producing Th2 clones. Because Th1 and Th2 clones can usually be detected only after several months of culture, we used conditions that modulate the IL-2 and IL-4 production in short term culture. Here we show that freshly isolated and subsequently in vitro-activated CD4+ T cells that were cultured for 11 days with rIL-2 and restimulated showed a IFN-gamma+ IL-2+ IL-3+ IL-4- IL-5- pattern. Because these cells were not capable of providing B cell help for IgG1, IgG2a, or IgE in an APC- and TCR-dependent T-B cell assay, they expressed a phenotype typical for most Th1 clones. In contrast, activated T cells that were cultured for 11 days with IL-2 plus a mAb to CD3 and then restimulated produced a IFN-gamma- IL-2- IL-3+ IL-4+ IL-5+ pattern. These cells were capable of providing B cell help for IgG1, IgG2a, and IgE synthesis and thus presented a phenotype typical for Th2 clones. Similar results were observed when mitogenic mAb to Thy-1.2 or to framework determinants of the alpha beta TCR were used. The induction of Th1- and Th2-like cells did not depend on the relative expression of CD44 or CD45 by the T cells before activation in vitro. Because the incubation of activated T cells with anti-CD3/TCR mAb induced high unrestricted lymphokine production, the latter might be responsible for the Th2-like lymphokine pattern observed after restimulation. To address this point, TCR V beta 8+ and V beta 8- T cell blasts were co-cultured in the presence of mAb to V beta 8. After restimulation, V beta 8+ cells had a IL-4high IL-2low phenotype and V beta 8- cells had a IL-4low IL-2high phenotype. This demonstrates that TCR ligation but not lymphokines alone are capable of inducing Th2-like cells, and this points out a central role for the TCR in the generation of T cell subsets.

Animals↗

Arthroscopy and chondrocalcinosis.

Different pathogenetic factors have been associated with the development of chondrocalcinosis. Under normal conditions, previous degenerative meniscus changes with proliferation of "pseudochondrocytes" and chondrocalcinosis have been found coincidentally. Small fragments can be excised during arthroscopy for histological assessment of the developmental stages and localization of chondrocalcinosis. We investigated 3,350 specimens histologically and correlated the results with clinical data and data on previous trauma to establish the role of surgery or trauma in the induction or promotion of chondrocalcinosis. The findings allow us to draw the conclusion that contrary to previous study findings, chondrocalcinosis is a highly significant factor in posttraumatic and/or degenerative meniscal changes.

Adult↗

Electrosurgery in arthroscopy.

Electrosurgery using high-frequency (HF) technique in arthroscopic operations has been used routinely in our hospital for 8 years. Main indications are meniscal resections, lateral release, plica cutting, and arthrolysis. The main instrument is a hook, which is insulated up to the tip and also cuts meniscal tissue. The cutting effect depends on the strength of the electrical current, the configuration of the hook-knife, and the cutting speed. The advantages of the electric knife over mechanical instruments are the ability to cut in all directions without resistance and easy manipulation within narrow joint spaces. Also, the necrotic depth of the meniscal cartilage is not excessive. Follow-up studies in 940 cases greater than 1 year after arthroscopic meniscal surgery did not show any significant difference in the results with or without use of the electric knife.

Arthroscopy↗