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Biomedical subjects

B Voss

Publications and source records attributed to B Voss.

At least 37 records · Page 2Linked to original sources
PubMed1998

Hepatocyte growth factor/scatter factor and its receptor c-Met are overexpressed and associated with an increased microvessel density in malignant pleural mesothelioma.

Hepatocyte growth factor/scatter factor (HGF/SF) stimulates cell proliferation, motility and invasiveness via its receptor c-Met during embryogenesis and repair processes. It induces angiogenesis, promoting endothelial cell migration and capillary-tube formation in vivo. Co-expression of HGF/SF and c-Met receptor results in enhanced tumour growth, invasiveness and a mesenchymal-epithelial transition in some experimental tumours. Since mesothelioma cells have been reported to express c-Met receptor and to migrate in response to HGF/SF, we investigated human malignant pleural mesotheliomas for the demonstration of possible co-expression of the growth factor and its receptor. The microvessel density of the tumours was also analysed in order to assess the influence of HGF/SF expression on tumour angiogenesis. Thirty-nine paraffin-embedded specimens of malignant pleural mesotheliomas were immunostained by anti-HGF/SF and anti-c-Met antibodies and semiquantitatively evaluated. c-Met mRNA expression was visualised in ten tumour samples by a fluorescent in situ hybridisation method. Microvessel density was calculated by counting microvessels with a high-power field (200x) on von-Willebrand-factor-stained slides. We found an increased production of HGF/SF in 33/39 tumours and a corresponding overexpression of c-Met receptor in 29/39 specimens. The FISH method detected increased transcription of c-Met mRNA in malignant cells and in neighbouring vascular endothelial cells. HGF/SF-positive mesotheliomas had significantly higher microvessel densities compared to their HGF/SF-negative counterparts. The observed co-expression of HGF/SF and c-Met in malignant pleural mesotheliomas suggests a possible self-stimulation (autocrine loop) of tumour cells. On the basis of the significantly higher microvessel density values of malignant mesotheliomas overexpressing HGF/SF, we postulate, that HGF/SF may be an additional relevant factor in tumour angiogenesis in malignant pleural mesotheliomas.

Hepatocyte Growth Factor↗
PubMed1998

Supernatants from quartz dust treated human macrophages stimulate cell proliferation of different human lung cells as well as collagen-synthesis of human diploid lung fibroblasts in vitro.

Silicosis is a chronic lung disease, which is caused by inhalation of silica-containing dusts, leading to pulmonary fibrosis. Alveolar macrophages play a key-role in defence against these particles entering the lung. As a result of phagocytosis, the macrophages release mediators, which are involved in various processes of inflammation and immunological defence mechanisms. We established an in-vitro test system composed of human macrophages, human pneumocyte type II cells (line A-549), human diploid lung fibroblasts (line Wi38) and human tracheobronchial epithelial cells (line BEAS-2B). With this model, we were able to study the influence of various cytokines, produced by the macrophages, on cell proliferation and collagen synthesis (only fibroblasts) of the cells in our test-system. In this report, we will summarize data obtained from our in-vitro test system on two cytokines, which are thought to be important in pathogenesis of lung fibrosis: insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta (TGF-beta).

Cell Division↗
PubMed1997

Expression of type IV collagenase correlates with the expression of vascular endothelial growth factor in primary non-small cell lung cancer.

Tumor growth and metastasis are angiogenesis-dependent processes initiated and regulated by a number of cytokines. Vascular endothelial growth factor (VEGF) is a potent angiogenic protein with a selective mitogenic effect on vascular endothelial cells, known to be involved in physiological (embryogenesis) and pathophysiological (rheumatoid arthritis, tumor) angiogenesis. An increased expression of matrix metalloproteinase type IV collagenase has been reported in invading endothelial cells in vitro and in malignant cells, degrading structures of the basement membranes in various human malignancies. In the present study we investigated the expression of the genes for type IV collagenase and vascular endothelial growth factor (VEGF) in 40 cases of primary non-small-cell lung cancer (NSCLC). Specimens were immunostained by an antibody directed against VEGF and mRNA transcripts of VEGF and type IV collagenase were localized by non-radioactive in situ hybridization. VEGF mRNA was detected in 33 neoplasms, while in 23 cases transcripts of the type IV collagenase gene were visualized by digoxigenin-labeled cDNA probes. Transcripts of both mRNAs were detected in malignant cells. Furthermore, anti-VEGF immunostaining was present in newly formed microvessels close to the atypical cells, and mRNA of type IV collagenase was present in stromal cells adjacent to the tumor. A statistically significant correlation was found between the expression of type IV collagenase and VEGF (P = 0.0061). These data suggest a double role for type IV collagenase in the metastatic process of NSCLC: (1) facilitating the invasion of tumor cells by the proteolytic cleavage of the basement membrane and (2) similarly supporting the endothelial cell invasion essential for tumor angiogenesis. Furthermore, our findings sustain the hypothesis that metastatic spread and angiogenesis are associated with a clonal expansion of highly angiogenic and invasive tumor cell clones.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

Simultaneous restitution of matrix and cells in gastric ulcer: use of a combined in-situ hybridization and immunohistochemistry technique applicable to paraffin-embedded tissue.

The restoration of gastric tissue after ulceration involves cellular and matrix components. Our aim was to investigate the kinetics of collagen expression and cellular proliferation in an animal model of gastric ulcer. To demonstrate the expression of type I and IV collagen mRNAs by proliferating cells, a method combining in-situ hybridization and immunohistochemistry was devised. In order to avoid the disadvantages of radioisotopes, digoxigenin-labeled RNA-riboprobes were utilized and combined with single-step immunohistochemistry. This method proved sensitive enough to detect type I and IV procollagen mRNA transcripts in the submucosal area beneath the ulcer crater or adjacent to the ulcer rim. In addition, a subset of cells transcribing either procollagen type I or IV RNA was concomitantly positive for proliferating cell nuclear antigen by immunohistochemistry. Focal proliferation of cells simultaneously expressing extracellular matrix components may therefore occur in the gastric submucosa after ulceration, starting as soon as 3 days after the insult and continuing for several weeks. The devised method of combined in-situ hybridization and immunohistochemistry can be used with standard paraffin-embedded tissues, yields results within 2 days, and avoids radioisotopes.

Acetic Acid↗
PubMed1997

A method to improve the latency estimation of the frequency-following potential (FFP).

If the latency of a noisy frequency-following potential (FFP) is estimated by determining the shift of the (periodical) cross-correlation function (CCF) between the stimulus and the FFP, the result may be unambiguous only within +/-1 or +/-2 periods of the CCF, because the absolute maximum and adjacent local maxima may not be significantly different. Here we present a method to amplify this difference by applying amplitude modulated stimuli. Using this method we first illustrate the effect of the method by a simulation and then demonstrate its usefulness by measuring real FFPs and estimating their latencies.

Artifacts↗
PubMed1997

Effect of early treatment with praziquantel on serum connective tissue metabolite markers in children and adolescents with intestinal schistosomiasis mansoni.

This work was designed to assess the reflection of early treatment by praziquantel (CAS 55268-74-1, EMBAY 8440, Biltricide) on serum connective tissue metabolite markers (hyaluronic acid and procollagen III peptide) in patients with active intestinal schistosomiasis. Children and adolescent subjects from primary and secondary schools in an endemic area of schistosomiasis mansoni were included. Age-matched subjects from an urban area served as normal controls. All subjects were examined clinically and parasitologically. Detection of hepatitis B seromarkers was also done. The infected subjects were treated with praziquantel at a dose of 60 mg/kg of body weight which was repeated after 4 weeks. Serum hyaluronic acid and procollagen III peptide were measured by radioimmunoassay. High hyaluronic acid was encountered in infected subjects when compared to their respective age-matched controls. Significant decrease of 4 and 8 weeks post-treatment was noted when compared to ist level before treatment. There was no significant change in serum procollagen III peptide on comparing infected subjects to their controls, whereas a significant increase was observed in its level after 4 and 8 weeks post-treatment compared to that before treatment. This work suggests that early treatment of intestinal schistosomiasis with specific chemotherapy (praziquantel) decreases serum hyaluronic acid and increases procollagen III peptide probably via downregulation of granulomatous inflammatory cell reaction and activation of collagenase enzymes, respectively.

Adolescent↗
PubMed1996

Expression of tumor necrosis factor-alpha and transforming growth factor-beta 1 in cerebrospinal fluid cells in meningitis.

Meningitis is an acute inflammatory disease of the pia and arachnoid and the fluid in the subarachnoid space, in which a participation of cytokines can be expected. While tumor necrosis factor-alpha (TNF alpha) promotes inflammatory reactions, transforming growth factor-beta 1 (TGF beta 1) has antagonistic effects and suppresses the inflammation in the subarachnoid space. We investigated the protein concentration and mRNA expression of TNF alpha and TGF beta 1 in cerebrospinal fluid (CSF) by ELISA and intracellularly by non-radioactive in situ hybridization in 23 patients with bacterial or viral meningitis. A higher amount of both cytokines on protein and mRNA level, especially of TNF alpha, could be detected in bacterial infection. While an imbalance of both cytokines with a preponderance of TNF alpha- compared to TGF beta 1-mRNA was visible in CSF cells of patients with bacterial meningitis, a balance of TNF alpha- and TGF beta 1-mRNA or a higher expression of TGF beta 1-mRNA could be detected in viral meningitis. In the acute phase of the disease neutrophil granulocytes expressed more TNF alpha- and TGF beta 1-mRNA than lymphocytes and monocytes/macrophages, while these cell types were dominating the cytokine synthesis during the healing phase. These data indicate that immunomodulatory mechanisms take place in the CSF compartment itself, regulated by CSF cells in different but specific ways. In addition, TGF beta 1 seems to be involved in the down-regulation of the inflammatory activity and to be one factor in the cytokine network, which could contribute to a lower rate of complications and positive outcomes. Moreover this study favors the possibility to monitor the immunomodulatory mechanisms by non-radioactive in situ hybridization.

Adult↗
PubMed1996

Protein components of a rat brain synaptic junctional protein preparation.

Antisera against a rat brain synaptic protein preparation, the postsynaptic density (PSD) fraction, were used to isolate cDNA clones by expression screening of a rat brain cDNA library. About one fifth of more than 200 analyzed cDNAs encoding potential synapse-associated proteins were previously unknown. Identifiable proteins include, among others, components of the pre- and postsynaptic cytoskeleton, synaptic vesicle proteins and several protein kinases and kinase substrates. This demonstrates that both pre- and postsynaptic elements purify with the PSD fraction.

Animals↗
PubMed1996

Long-term follow-up after high-activity 125I brachytherapy for pediatric brain tumors.

A retrospective review including long-term follow-up (4.6-12.0 years) was performed of all 28 pediatric patients who underwent high-activity 125I brachytherapy at the University of California, San Francisco, for primary or recurrent brain tumors from 1980 until 1991. There were 4 glioblastomas, 11 high-grade nonglioblastoma multiforme (NGM) malignant gliomas, 10 contrast-enhancing low-grade NGM, 2 choroid plexus carcinomas, and 1 rhabdomyosarcoma. The 13 survivors included 7 of 8 patients with primary high-grade NGM, 2 of 3 patients with primary low-grade NGM, and 3 of 7 patients with recurrent low-grade NGM. Necrosis (with or without tumor) was identified in 17 of 22 reoperated patients. The mean Karnofsky performance status was 88 +/- 9 at the time of brachytherapy, 87 +/- 7 at 3 years, and 87 +/- 9 in 11 patients alive at 6-12 years. Brachytherapy is a useful modality for treating selected pediatric brain tumors, and although focal necrosis is a common sequela, it does not tend to have a major impact on the Karnofsky performance status, if the implant site is amenable to reoperation.

Adolescent↗
PubMed1996

[Characterization of structural and cellular components in pulmonary sarcoidosis granuloma].

Granulomas occurring in sarcoidosis with lung involvement are mostly located in the paravasal interstitium, pleura, bronchial mucosa and stroma. The phases and the activity of the disease process are characterised by different patterns from multicellular epitheloidcellular granulomas to marked hyalinisations and scarifications. For the purpose of histochemical characterisation of the composition of the cells and matrix of pulmonary granulomas in open and transbronchial lung biopsies of 15 patients suffering from sarcoidosis in different clinical stages, antibodies were employed against macrophages, neutrophil elastase, collagen types I and III, fibronectin, laminin, PCNA and against the tumour suppressor gene product P53. Identification was subsequently performed either by means of indirect immunofluorescence or the PAP technique. Multicellular granulomas showed, especially centrally, a specific fluorescence for macrophages involving also giant cells, whereas antibodies against neutrophil elastase could be mainly identified peripherally. PCNA and P53 protein were identified in the cytoplasm and partly also in the nuclei of giant cells. Collagen types I and III were mainly expressed pericentrally. Fibronectin was found in numerous multicellular epitheloid cellular granulomas not only in the peripheral collagen network but also centripetally oriented. The scarifying granulomas showed initially increased centripetal deposition of fibronectin followed by an addition of collagen types I and III. Laminin was always present in very small quantities only. The results obtained demonstrate a variable expression of matrix structures in sarcoidosis, dependent on the developmental stages of pulmonary granulomas, this expression being capable of control to some extent with the proportions of epitheloid cells, lymphocytes and macrophages that are present. Tumour suppressor gene p53 positive macrophage giant cells and adhesion molecules such as fibronectin participate in granuloma production to a varying extent.

Biopsy↗
PubMed1996

Piccolo, a novel 420 kDa protein associated with the presynaptic cytomatrix.

In this study, we describe a novel 420 kDa protein, called Piccolo, found at a wide variety of adult rat brain synapses. High protein levels in the cerebellum, the olfactory bulb and the hippocampus were frequently observed to be associated with asymmetric type 1 synapses. Piccolo is selectively enriched in presynaptic terminals, but is not a component of synaptic vesicles (SVs). Immunogold electron microscopy revealed that Piccolo localizes to the amorphous material among SVs at the presynaptic plasma membrane. Biochemical studies showed that it is very tightly bound to this structure. Thus, we speculate that Piccolo is a structural component of the presynaptic cytomatrix which anchors SVs to the presynaptic plasmalemma.

Animals↗
PubMed1995

P53 accumulation and proliferating-cell nuclear antigen expression in human lung cancer.

Mutations in the p53 gene are currently the commonest genetic alterations in human malignant tumors, including non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Alterations of the protein induced by gene mutations enables the mutant protein to become more stable, resulting in the accumulation of P53 in quantities detectable by immunohistochemistry. Although previous studies document the accumulation of P53 in lung cancer, there is little information regarding the usual frequency of accumulation based on a comprehensive number of lung tumors. A total of 328 paraffin-embedded lung carcinoma specimens were analyzed for P53 accumulation and for the expression of the proliferating-cell nuclear antigen (PCNA) by standard immunohistochemistry. Among 49 SCLC, 35% were positive for p53 and 51% were positive for PCNA. Out of 279 NSCLC, 43% showed a positive P53 immunoreaction and 72% displayed detectable amounts of PCNA. In squamous-cell carcinomas a statistically significant increased accumulation of P53 was found compared to adenocarcinomas (P = 0.001). Among the 233 PCNA-positive tumors the relative number of P53-positive specimens was higher compared to the total number of tumors. Since immunohistochemical investigations should contribute to the improvement of the clinical diagnosis and treatment or give information on the prognosis, we conclude from our results that it seems to be legitimate to assess the P53 status exclusively in the specimens positive for PCNA. Immunohistochemical investigations under consideration of the PCNA status yielded good and fast recognition of p53 mutations leading to intracellular P53 protein accumulation.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

Treatment of dilated cardiomyopathy with dynamic cardiomyoplasty: the Heidelberg experience.

BACKGROUND: Data concerning the efficacy of dynamic cardiomyoplasty are still inconsistent, especially in terms of improvement of left ventricular function. METHODS: Between August 1990 and February 1994, eight isolated cardiomyoplasty procedures were performed in patients with cardiomyopathy (ejection fraction, 0.14 to 0.32; New York Heart Association class III) and contraindications to heart transplantation. RESULTS: Follow-up was 41.1 +/- 14.1 months. One patient died 2 months and another 3 years after operation. Considerable symptomatic improvement was found in 6 of 7 patients, 3 of whom went back to work. One patient with severe pulmonary hypertension exhibited no improvement. Mean New York Heart Association-class decreased from 3.0 to 1.9 (p < 0.001). Echocardiography showed an increase in fractional shortening and in peak aortic flow velocity in all patients. Left ventricular ejection fraction increased from 0.21 +/- 0.05 to 0.38 +/- 0.16 (n = 7, p < 0.015) at 1 year, to 0.37 +/- 0.18 (n = 6, p < 0.05) at 2 years, and to 0.36 +/- 0.19 (n = 5, not significant) at 3 years. Pulmonary artery pressure tended to decrease over time. No significant change in exercise level or maximal oxygen consumption during treadmill testing was observed. CONCLUSIONS: Our preliminary results show that patients may exhibit an impressive clinical improvement after cardiomyoplasty, with only moderate changes in objective hemodynamic indices. We do not consider cardiomyoplasty an alternative to heart transplantation, but reserve it for patients with contraindications to heart transplantation.

Cardiomyopathy, Dilated↗
PubMed1995

Dynamic cardiomyoplasty: indication, surgical technique, and results.

The efficacy of dynamic cardiomyoplasty is still controversial. To date more than 400 patients have been operated worldwide. In recent years the indication and the surgical technique have become more uniform, which makes results from different centers eligible for comparison. We performed cardiomyoplasty exclusively in patients with contraindications for heart transplantation, such as chronic and recurrent infections or severe, irreversible sequelae of diabetes. Between August 1990 and October 1994, 8 isolated cardiomyoplasty procedures were performed in patients with cardiomyopathy (EF 14-32%, all in NYHA III). One patient died 2 months after surgery. Reported are the results of 7 patients after a mean follow-up of 41.1 +/- 14.1 months. Considerable symptomatic improvement was found in 6 or 7 patients, 3 of whom went back to work. One patient with severe pulmonary hypertension exhibited no improvement. In the others NYHA class improved by at least one. Echocardiography showed an increase in fractional shortening in all patients. LVEF increased from 21.2 +/- 5.2% to 38.1 +/- 15.9% (n = 7, p < 0.015) at 1 year, to 36.6 +/- 17.6% (n = 6, p < 0.05) at two years, and to 36.4 +/- 18.9% (n = 5, NS) at three years. Pulmonary artery pressure tended to decrease at rest over time. Resting lung function showed no change of vital capacity and FEV1. No significant change in exercise level and maximal O2-consumption during treadmill testing was observed. One patient died 34 months after the operation from sudden death. Our preliminary results show that patients after cardiomyoplasty may exhibit an impressive clinical improvement with less striking changes of objective hemodynamic parameters. This data is in agreement with the results of all other investigators. Some possible mechanisms of action are discussed and a risk profile suggested. According to the current state of experience with cardiomyoplasty, we do not consider this method an alternative to heart transplantation, but reserve it for patients with contraindications for heart transplantation.

Cardiomyopathies↗
PubMed1995

[Induction of rat liver foci by inhaled diisocyanate exposure].

Diisocyanates are increasingly used for manufacturing polyurethane foam, elastomers, adhesives, coatings, insecticides and many other products. The large number of workers being exposed to these chemicals has a concentration-dependent risk of developing chronic airway disorders. The clinical role of genotoxic effects of diisocyanates demonstrable in vivo and in vitro is still unclear just as their possible cancerogenic potential. The possible initiating effect of diisocyanates in liver carcinogenesis was studied using a rat liver foci bioassay (RFLA). The RLFA is based on the histochemical demonstration of foci of hepatocytes with altered enzyme equipment, which are induced by carcinogens. These foci are generally regarded as early preneoplastic lesions. Rats were exposed either to 20 ppb TDI (Toluene diisocyanate) or 20 ppb HDI (Hexamethylene diisocyanate) for two hours a day over a period of four weeks. After a break of one week the rats received 10 mg Clophen A50/kg body weight as promotor for possible isocyanate induced tumorigenic lesions twice a week for eight weeks. For positive control the hepatocarcinogen diethylnitrosamin (DEN) was given as a single dose of 10 mg and 20 mg. All animals were sacrificed aged 16 weeks. Serial cryostat sections were prepared for ATPase and gamma GT staining. The foci number was determined and calculated as foci/animal as a mean value taken from both staining protocols. Preneoplastic liver foci were observed in positive control rats treated with a single dose of 10 mg as well as with 20 mg DEN (4.3 +/- 3.2 and 1.8 +/- 1.4 respectively). In none of the animals exposed to TDI or HDI preneoplastic foci were detectable.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants, Occupational↗