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Biomedical subjects

K M Müller

Publications and source records attributed to K M Müller.

At least 199 records · Page 11Linked to original sources
PubMed1994

[Collagens and growth factors in heterotopic ossification].

Heterotopic Ossification (HO) occurs as a consequence of several diseases and of various forms of trauma. HO is particularly frequent in paraplegic patients with spinal cord lesions. It is obvious that extraskeletal cells are able to differentiate into an osteogenic direction. However, the mechanisms of the induction process of HO and the stimulating agents are not precisely known. A novel tool for studying the ossification process at the level of transcription is the technique of non-radioactive in situ hybridisation. Using digoxigenin labeled cDNA probes we investigated the distribution patterns of types I, II and III collagen mRNAs and the mRNA of Transforming Growth Factor beta 1 (TGF-beta 1) in heterotopic ossification of pressure sores of paraplegic patients. The three collagen mRNAs as well as the TGF-beta 1 mRNA exhibited substantially divergent distribution patterns. Type I (alpha 1) collagen mRNA was predominantly detectable in preosteoblasts, chondroblasts and chondrocytes of the ossification zone. Type II (alpha 1) collagen mRNA was nearly exclusively found in cells of the chondrogenic lineage. Type III (alpha 1) collagen mRNA was detectable at low levels in soft tissue, but was strongly expressed by chondroblasts and chondrocytes of heterotopic cartilage. In contrast expression of TGF-beta 1 mRNA was found in a spatial different distribution pattern in areas of proliferation of mesenchymal tissue and in different stages of ectopic bone formation. As in the case of collagen Type I (alpha 1) and III (alpha 1) mRNAs the maximum of localization of TGF-beta 1 was detected in chondroblastic areas of heterotopic ossification. Taken together our in situ hybridization experiments provide evidence that chondrogenic cells play a central role in the process of HO with a phenotypic alteration in collagen type expression and a strong expression of TGF-beta 1 mRNA. These findings support individual in vivo function for TGF-beta 1 in local cellular regulation of ectopic bone formation.

Cartilage↗
PubMed1994

[Oncogenes and tumor suppressor genes in the pathogenesis of lung tumors].

The recent results obtained from investigations based on molecular biological techniques have led to a better understanding of recurrent genetic causes important for the pathogenesis of tumors. Several genes have been identified as being involved in the development of cancer. In many cases, the activation of oncogenes or the inactivation of tumor-suppressor genes is the predominant reason for cancerogenic cell transformation. Functional dysregulation is frequently the consequence of mutations, resulting in an alteration of the primary structure of the DNA. As our understanding of the nature, function, and interaction of these genes evolves, new opportunities for early diagnosis, classification, prevention, and treatment of malignant tumors will arise. The present report summarizes the current molecular biological aspects of several oncogenes (erbB, ras, myc, raf, fos, jun, bcl, mdm2, myb, kit CSF1R, met) and tumor suppressor genes (p53, rb, mts) involved in lung-cancer development with respect to the pathology of lung tumors, including the importance of these genes as far as the clinical course of the disease is concerned.

Cell Transformation, Neoplastic↗
PubMed1994

[Pulmonary lymphangioleiomyomatosis in tuberous sclerosis].

Pulmonary lymphangioleiomyomatosis was diagnosed in a 26-year-old woman with recurrent pneumothorax by histological evaluation of a lung biopsy obtained during video-thoracoscopy. A tumour of the right kidney had been removed 2 years previously; the histological picture was that of an angiomyolipoma. Immunohistochemical staining for anti-smooth muscle actin gave a strongly positive reaction in the tissue of the renal angiomyolipoma and in the pathologic lung tissue. Additional investigations showed an asymptomatic intracerebral tumour 5 cm in diameter in the left frontal lobe (brain scan). This multilocal renal, pulmonary and cerebral manifestation of benign mesenchymal proliferating tumours supports the classification of this case in the tuberous sclerosis complex.

Adult↗
PubMed1994

Lendrum (-MSB) staining for fibrin identification in sealed skin grafts.

The significance and effect of fibrin sealant systems for woundhealing are still unknown, because of the use of insufficient, conventional staining methods for the demonstration of the fibrin components used by sealant systems. From 21 patients with extensive burns of 2nd and 3rd degree biopsies of the skin were obtained during consecutive operations to cover the defect of the skin with split-thickness skin grafting. In the present paper morphological results concerning the demonstration of fibrin components and morphological differences in woundhealing of sealed and unsealed skin grafts are presented using Lendrum (-MSB) staining. With this staining method it is possible to identify exogenous fibrin components of the sealant system and to differentiate between fresh and older fibrin components, due to colour changes depending on time.

Azo Compounds↗
PubMed1994

AgNOR counts in preneoplastic lesions of the bronchus.

Silver staining of argyrophil nucleolar organizer regions (AgNORs) has become a valuable method to assess cell kinetics in paraffin sections and separate benign from malignant lesions. As a putative technique for the distinction between regenerative and preneoplastic alterations of the bronchial mucosa we employed the Ag-staining method, evaluating the number of dots/nucleus and shape of the dots. Dots/nucleus were counted by by standardized methods, and mean and standard deviation were calculated. Comparative investigations were performed in bioptically obtained specimens of normal bronchial epithelium (1.94 +/- 0.1 dots/nucleus, n = 12), basal cell hyperplasia (2.22 +/- 0.13 dots/nucleus, n = 15), goblet cell hyperplasia (2.38 +/- 0.16 dots/nucleus, n = 17), squamous cell metaplasia (2.58 +/- 0.17 dots/nucleus, n = 25), squamous cell metaplasia with mild and moderate dysplasia (2.50 +/- 0.5 dots/nucleus, n = 15), squamous cell metaplasia with severe dysplasia and carcinoma in situ (3.10 +/- 0.47 dots/nucleus, n = 17), micropapillomatosis (2.20 +/- 0.21 dots/nucleus, n = 13) and early squamous cell carcinoma of the bronchus (4.40 +/- 0.74, n = 13). In preneoplastic lesions a variability in form and size of the dots was found. Though showing an increase in the number of dots/nucleus coincidentally with the degree of proliferative activity, the AgNOR method cannot be considered as a statistically significant tool in the evaluation of regenerative and preneoplastic lesions in bioptically obtained specimens.

Bronchi↗
PubMed1994

Localization of collagen types I, II, and III mRNAs in human heterotopic ossification by non-radioactive in situ hybridization.

Heterotopic ossification is a metabolically active process which shares several properties of orthotopic bone formation and, therefore, represents an excellent model for the investigation of matrix components. A novel tool for studying the ossifying process at the level of transcription is the technique of non-radioactive in situ hybridization. Using digoxigenin labeled cDNA probes we investigated the distribution patterns of types I, II and III collagen mRNAs in heterotopic ossification of pressure sores of paraplegic patients. The three collagen mRNAs exhibited substantially divergent distribution patterns. Type I (alpha 1) collagen mRNA was predominantly detectable in preosteoblasts, prechondroblasts and chondrocytes of the ossification zone. Type II (alpha 1) collagen mRNA was nearly exclusively found in cells of the chondrogenic lineage. Type III (alpha 1) collagen mRNA was detectable at low levels in soft tissue, but was strongly expressed by prechondroblasts and chondrocytes of heterotopic cartilage. Our in situ hybridization experiments provide evidence that chondrogenic cells in heterotopic ossification show a phenotypic alteration in collagen type expression. These results indicate that chondrocytes of heterotopic cartilage show a co-expression of types I (alpha 1), II (alpha 1) and III (alpha 1) collagen mRNAs.

Collagen↗
PubMed1994

The perivascular connective matrix.

The functional properties of the perivascular matrix facilitate the movement, protection and the nutrition of the blood vessels. At the same time the matrix deliniates the vessels to the organs. Different vascular diseases of the vascular system implicate the perivascular matrix consisting of a network of structural and cellular connective tissue components. Impairment of its structural integrity predominantly occurs either from primary or secondary affections. Monospecific antibodies directed against different structural proteins enable detailed histomorphological examinations of the inflammatory tissue reaction in the perivascular space. Since myofibroblasts, fibrocytes, endothelial cells, and macrophages participate in tissue repair mechanisms, in vitro studies on the collagen synthesis may contribute to the understanding of the perivascular tissue reaction according to injury. The present report summarizes perivascular diseases and the in vitro synthesis of procollagen, collagen, and fibronectin of endothelial cells, fibroblasts, smooth muscle cells, and macrophages.

Animals↗
PubMed1994

Morphological and clinical aspects of heterotopic ossification in sports. A case study.

Heterotopic ossification (HO) caused through sport injuries is a rare, clearly defined lesion. In a considerable number of cases, however, no adequate trauma can be remembered or otherwise established in the "sporting history". Differential diagnosis of this non-traumatic HO variant often presents many problems which may lead to the wrong diagnosis of sarcoma. We looked at 28 cases, in which in more than 50% a sarcoma was discussed as primary diagnosis. These difficulties arise mainly in cases where clinical features suggest a tumor, radiological changes are unspecific, and the diagnosis is based on a small biopsy sample. We demonstrate and discuss the problems involved in differential diagnosis using the history of a matchgrade sportsman as a sample. Unlike in sarcoma, patients with HO usually suffer severe pain, and well over 50% of all patients develop the disease during the 2nd or 3rd decade. Over 90% of all patients with soft tissue sarcoma, however, are over the age of 30. From the morphological point of view, the different histological pattern of HO has to be taken into account, since early stages may mimick a sarcomatous lesion. If the clinical findings suggest the presence of HO, surgical intervention including the taking of biopsy sample should be postponed, so that instead of early highly mitotic active phases more mature bone structures, which are easier to classify, will be available for evaluation. Only a profound knowledge of the different phases of HO, together with clinical and radiological features, will clarify the differential diagnostic problems of the non-traumatic variant of this lesion in sportsmen.

Adult↗
PubMed1994

cAMP up-regulates IL-4 and IL-5 production from activated CD4+ T cells while decreasing IL-2 release and NF-AT induction.

Seven days after activation with concanavalin A and irradiated spleen cells, murine CD4+ T cells were re-stimulated with ionomycin and phorbol 12-myristate 13-acetate (PMA). IL-2 and IL-4 were determined in the supernatant. When cholera toxin, forskolin together with phosphodiesterase inhibitors or dibutyryl-cAMP were added at the time of re-stimulation, a dose-dependent increase of IL-4 and IL-5 release was noted. IL-2 was down-regulated as reported before. The up-regulation of IL-4 and the down-regulation of IL-2 correlated with an increase of IL-4 mRNA and a decrease of IL-2 mRNA as determined by semi-quantitative reverse transcriptase polymerase chain reaction. Similar results were found with prostaglandin E2 using PMA and ionomycin or plate-bound anti-CD3 antibody as re-stimulants. These results suggest that, in activated CD4+ T cells, cAMP-elevating agents induce a switch of lymphokine production towards a Th2-like phenotype through regulation at the transcriptional level. This is supported by the fact that complex formation between a synthetic nuclear factor of activated T cells (NF-AT) binding site from the IL-2 promoter and nuclear extracts was decreased when cholera toxin was added to re-activated CD4+ T cells, suggesting that cholera toxin and cAMP down-regulate IL-2 expression via decreased NF-AT binding. Finally, since IL-4 has been reported to amplify IL-4 release from activated CD4+ T cells, the autoinduction of IL-4 may very well function via cAMP.

Animals↗
PubMed1994

A rare manifestation of von Recklinghausen neurofibromatosis: advanced neurofibromatous infiltration in lung of a HIV-positive patient.

This is a report of a 28-year-old HIV+ man with extensive involvement of lungs, spinal roots and peripheral nerves by neurofibromatosis von Recklinghausen. Huge masses (neurofibromas) ventral of the spine, which already infiltrated into the foramina intervertebralia, could be located by magnetic resonance imaging and high resolution computer tomography. Strikingly, most biopsies taken by bronchoscopy of the bronchial wall from various parts of the airways revealed extended infiltration by neurofibromas in submucosal areas, but no malignant tissue components. In addition, HIV infection with low CD4/CD8 ratio (0.1) and low CD4+ cells (160/microliters) was found.

Adult↗
PubMed1994

Response element selectivity for heterodimerization of vitamin D receptors with retinoic acid and retinoid X receptors.

The transcription of vitamin D (VD) responsive genes is regulated by three different nuclear signalling pathways mediated by homodimers of VD receptors (VDRs), heterodimers of VDRs and retinoid X receptors (RXRs) and heterodimers of VDRs with retinoic acid receptors (RARs), Here, the in vitro DNA-binding affinity of all three receptor complexes was shown to be enhanced by the presence of VD. However, the specificity of the three pathways was dictated by the differential affinities of the receptor complexes for VD response elements. Potential response elements were distinguished by the sequence, the separation and the relative orientation of the hexameric core binding motifs. It was found that both VDR-RAR and VDR-RXR heterodimers act functionally on all three response element configurations: direct repeats, palindromes and inverted palindromes. With direct repeats, neither heterodimer type showed a preference for any of the three principal core motifs, (A/G)GGTGA, (A/G)GGTCA and (A/G)GTTCA. However, while they did exhibit preferences for core motifs in palindromes, the spacing requirements were identical for both complexes. Inverted palindromes, however, formed the most specific response elements. A simple model explains a steric link between the optimal spacing of direct repeats and that of inverted palindromes. Taken together, the experimental data and the model provide further criteria for the screening of VD responsive genes.

Animals↗
PubMed1994

[Expression and secretion of alpha-2-macroglobulin by dust-stimulated alveolar macrophages].

In dust-induced, fibrosing lung processes macrophages are increased activated by foreign body reactions. The release of monokines and proteolytic enzymes, which depends on phagocytosis, may lead to destruction of the extracellular matrix with the consequence of degradation and restitution. Also the transcellular signaling or cell-matrix-interaction may finally result in development of fibrosis. However the proteolytic effect of elastase and collagenase can be inhibited by alpha-2-macroglobulin. Alpha-2-macroglobulin is a protease-inhibitor, which is synthesized by macrophages and has a wide spectrum of inhibitory abilities. Our interest was focused on observation of the production of alpha-2-macroglobulin by alveolar macrophages after stimulation with inorganic dusts of different chemical and physical properties. Rat alveolar macrophages were isolated by bronchoalveolar lavage and exposed to crocidolite, quarz or welder steam dust in vitro. The expression and secretion of alpha-2-macroglobulin was examined by non radioactive in situ hybridization, indirect immunofluorescence and radial immunodiffusion according to Mancini. The stimulated rat alveolar macrophages showed an increased expression of alpha-2-macroglobulin-mRNA and also an enhanced synthesis of alpha-2-macroglobulin-protein. Besides only small differences between the substances used for stimulation were demonstrated.

Animals↗
PubMed1994

[Surgery for bronchial carcinoma with mediastinal lymph node involvement].

Or the 3000 patients analyzed in the prospective bronchial carcinoma field study, 1086 were operated between 1984 and 1989. Complete systematic mediastinal lymphadenectomy was performed in 661 patients to assess the PTNM stage as exactly as possible, and to improve prognosis. Lymphadenectomy removes all hylarand mediastinal lymph nodes. Although the operation is technically quite easy on the clearly structured right side, it is more difficult on the left side due to the aortic arch and its branches. The lymph nodes of the upper mediastinum of the left and right side can be completely dissected by mobilizing the aortic arch with the left subclavian artery. In contrast to what is frequently assumed, the histological findings indicate that there is no general pattern of metastatic spread in the lymph nodes. The metastases can leave out varying numbers of lymph nodes craniad as well as caudad. For this reason, the lymph nodes have to be completely resected to ensure a real R0-resection.

Female↗
PubMed1994

[An unusual form of silicosis caused by exposure to a priming putty (Asplit ET)].

A case report on a 59-year-old male patient is given who had been exposed for 30 years to silica flour when mixing the primer Asplit ET. To some extent the diagnostic findings were uncommon for silicosis and rather suggested the diagnosis of a usual interstitial pneumonitis. Only transbronchial lung biopsy and histologic examination inclusive energy-dispersing x-ray microanalysis was able to prove a complicated form of silicosis.

Biopsy↗
PubMed1994

[Bronchiolitis obliterans after mycoplasma pneumonia].

Mycoplasmal pneumonias belong to the class of atypical pneumonias. Generally, the histomorphological findings are non-specific; occasionally there are fibrotic pulmonary changes in consequence of partial recovery. In the case under report we present a 27-year old male patient who developed an almost total atelectasis of the right lung subsequent to an unspecific respiratory infection. Serologically his findings were characterised by an extremely elevated mycoplasmal titre so that we had to assume he was suffering from mycoplasmal pneumonia taking an unusual course. Since it was not possible to restitute the lung despite intensive therapeutic efforts, right-sided pneumonectomy had to be performed. Histological examination of the resectate resulted in diagnosing a bronchiolitis obliterans with partially complete obliteration of the bronchi down to subsegmental size. The case presented here must therefore be interpreted as a rare course of mycoplasmal pneumonia associated with the development of a massive atelectasis on an underlying bronchiolitis obliterans.

Adult↗
PubMed1994

[Are video-assisted thoracoscopic resections in oncological surgery defensible?].

Video-assisted thoracoscopic surgery (VATS) is not to be accepted in oncologic patients at present. Up till now, the technical facilities are not as advanced as to compete with the established procedures of conventional surgery. The thoracoscopic, more indirect surgical methods are not able to adequately adjust to the specific growth pattern and paths of metastatic spread of bronchial carcinoma. Surgery for pulmonary metastasis has to be considered under the same aspects. Preoperative staging of lung cancer and the location and number of pulmonary metastases cannot be sufficiently assessed by computed tomography. Consequently, palpation of both the inflated and deflated lung is mandatory. Oncologic surgery includes complete lymph node dissection in all compartments, which cannot be achieved by VATS at present. It is irresponsible to risk the internationally quite homogenous stage-related results obtained in bronchial carcinoma for the sake of some new technical equipment. In surgery for lung metastasis, curative treatment demands to completely remove all lesions and the corresponding lymph nodes. This management alone promises benefit for the patient. VATS is established in 1) removal of coin lesions (change to open surgery in case of malignancy; 2) diagnostic resection in metastasis surgery. Results after VATS have to be assessed for quality control in VATS in the same way as it is done for open surgery.

Carcinoma, Bronchogenic↗
PubMed1994

[The recognition of osteofibrous dysplasia Campanacci. Morphology, radiology, clinical picture and therapy].

Radiologically osteofibrous dysplasia of the tibia is characterized by an eccentrically localized osteolytic lesion in the diaphysis with the appearance of ground glass. However, this is a very rare lesion, making a correct diagnosis difficult, especially since fibrous dysplasia and adamantinoma of the tibia have to be taken into account in the differential diagnosis of the disease. A definitive diagnosis can only be made histologically. The rather aggressive growth pattern of osteofibrous dysplasia as compared to fibrous dysplasia that has been reported in literature should not be generalized and it must be taken into consideration that surgery may be performed too early during the growth phase.

Child↗