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Biomedical subjects

M Kohler

Publications and source records attributed to M Kohler.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Scanning electron microscopy and microcrystals in articular diseases].

The value of scanning electron microscopy (SEM) in the study of crystals in articular diseases is underlined in several cases of examination of joint fluid, or crystal deposits in articular or periarticular tissues obtained by percutaneous or surgical treatment with chemical and crystallographic correlations. Apatite crystals. Two deposits of hydroxyapatite of the rotator cuff were studied by SEM, crystallographic techniques and chemical analysis. SEM study showed spherical aggregates of various size. Urate crystals. Three tophi were observed by SEM, with crystallographic techniques and chemical analysis. Their needle-shape and their great size (20 m) were characteristic. Calcium pyrophosphate crystals. In a case of typical clinical and radiological features, examination of joint fluid, with chemical correlation showed shorter and thicker crystals than those or urate. The precise identification of crystals is based on sophisticated crystallographic techniques such as X-ray diffraction, although SEM allows an accurate and quite simple morphologic study, most often sufficient.

Apatites↗
PubMed1992

Metastasizing lung carcinomas in Hann: Wistar rats.

In Hann:Wistar rats, 25 weekly subcutaneous injections of dipentylnitrosamine (DPNA) at doses of 0, 62.5, 125 and 250 mg/kg body weight induced lung carcinomas which metastasized partly. The incidence of the primaries was 2.5, 20.0, 77.5 and 100% in the males and 0, 0, 12.5 and 57.5% in the females, respectively. The frequency of metastases was 0, 12.5, 38.7 and 72.5% in the males and 0, 0, 40.0 and 52.2% in the females, respectively. The most common metastatic sites in males and females together were: lung-associated lymph nodes (82.1%), adrenal gland (53.6%), kidney (39.3%), pancreas (32.1%), bones (16.1%), heart (12.5%), mesentery (12.5%) and CNS (8.9%). In the females, metastases were also detected in the uterus (21.4%) and ovary (42.9%). The results indicate that: (1) through subcutaneous injections of DPNA metastasizing lung carcinomas can be induced with high incidence, and (2) the metastatic pattern is very similar to human cases. Thus, this model could be useful for the study of metastasizing lung carcinomas in experimental animals.

Adenocarcinoma↗
PubMed1992

Epidermal growth factor receptor and transforming growth factor alpha expression in human ovarian carcinomas.

The varying tumorbiological behaviour of ovarian carcinomas probably influences operability, response to chemotherapy, being one of the most relevant prognostic factors. Because it is believed that an activation of the epidermal growth factor/transforming growth factor alpha (EGF/TGF alpha) signal pathway could be involved, we analysed the expression of epidermal growth factor receptor (EGFR) and TGF alpha with molecular-chemical, biochemical and immunohistochemical methods in 42 ovarian carcinomas, 4 ovarian metastasis, 2 other malignant ovarian tumours, and in 25 nonmalignant tissues (ovary, myometrium). No major rearrangements or amplification of the EGFR or TGF alpha genes were found. In non-malignant tissues no strong EGFR or TGF alpha signals were detected. TGF alpha is mainly produced by the tumour cells as shown by immunohistochemistry. Four different high molecular weight forms (20-48 kD) were detected in malignant tissues by western blot analysis.

Blotting, Northern↗
PubMed1992

Mutations of the Ki-ras oncogene in endometrial carcinoma.

OBJECTIVE: The purpose of this study was to assess the extent of involvement of the ras oncogene in endometrial carcinoma. STUDY DESIGN: Genomic deoxyribonucleic acid from 30 samples of endometrial carcinoma was examined for point mutations in codons 12, 13, and 61 from the Ha-ras, Ki-ras, and N-ras genes by means of the polymerase chain reaction, slot-blotting, and deoxyribonucleic acid sequencing procedures. RESULTS: An apparent somatic mutation of Ki-ras codon 12 in one of 10 paraffin-embedded tumors was confirmed by deoxyribonucleic acid sequence analysis. Two of 20 frozen endometrial carcinoma specimens were also shown to contain a point mutation in Ki-ras codon 12. No correlation between ras mutation and a number of histologic or clinical parameters was observed. CONCLUSIONS: These data suggest a potential role for Ki-ras codon 12 mutations in the development of some (10%) endometrial cancers.

Cloning, Molecular↗
PubMed1992

Cytokeratin filaments of the liver of BALB/c mice as a sensitive marker of liver damage. Computer-aided characterization with the image analysing system "IBAS".

The cytoskeleton forms a complex structural network which is of major importance for both structural integrity and physiologic functions of the cell. The aim of the present investigation was to investigate whether hepatotoxic effects of nitrosamine and colchicine can be detected through changes in the cytokeratin filament system which is an important component of the cytoskeleton. Groups of 10 male and 10 female newborn BALB/c mice were treated with either 25 micrograms dimethylnitrosamine (DMN) injected intraperitoneally on the day of birth; or with a daily subcutaneous injection of 0.12 micrograms/kg b.w. colchicine starting at ten weeks of age. A third group of mice served as untreated controls. All animals were held under standard laboratory conditions until necropsy at 16 weeks of age. The group injected with DMN received 0.05% phenobarbital with their drinking water after weaning. The histologic changes in the liver tissue were characterized by light microscopy. Changes of the cytokeratin filaments were visualized by the indirect immunofluorescent technique and quantified by using the image analysing system "IBAS". The cytokeratin filaments in the DMN group were markedly increased in amount and had a variety of morphological alterations. These effects could be measured quantitatively and did not indicate any sex-dependent behavior. The colchicine group did not display any structural changes in the cytokeratin filaments but sex-dependent changes in the amount of keratin material was revealed by image analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗
PubMed1992

Oncogene and growth factor expression in ovarian cancer.

The varying tumor-biological behavior of ovarian carcinomas probably influences both their operability and response to chemotherapy, which are the most relevant prognostic factors. The phenotype of different ovarian carcinomas is obviously associated with an activation of the EGF/TGF-alpha signal pathway, including c-myc and c-jun expression. Analysis of EGF-R, TGF-alpha, c-myc and c-jun expression in 33 stage III/IV, and 2 stage I/II ovarian carcinomas with biochemical, molecular-chemical and immunohistochemical methods showed a correlation between the mRNA and protein levels of EGF-R and TGF-alpha for tumors with low or high expressing rates. However, the concentration of measurable free EGF-Rs seems to depend on the amount of TGF-alpha expression by the tumors. The EGF-R binding ligand TGF-alpha is produced by epithelial tumor cells; stromal cells are usually TGF-alpha-negative, as shown by immunohistochemistry. High expression rates of EGF-R. TGF-alpha and c-myc were detected in 6, 7, and 10 out of 35 ovarian carcinomas, respectively. C-jun mRNA was detected in 18/19 cases studied. Non-malignant tissues originating from myometrium or ovary expressed no (or only small amounts of) EGF-R or TGF-alpha mRNA, whereas a high c-myc expression was found in 1/7 normal myometria, and in 2/5 normal ovaries. There was no strong correlation between EGF-R/TGF-alpha and c-myc/c-jun expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗
PubMed1992

Urination frequency and cystic pressure resistance after fractionated whole or partial irradiation of the rabbit urinary bladder.

Urination frequency and cystic pressure resistance have been used as end-points to assess x-ray-induced changes of bladder function. Whole or half bladders of adult male rabbits were irradiated, caudally or cranially. The absorbed dose was 33 Gy, 36 Gy or 39 Gy, given in 5 daily fractions. Animals which received a whole bladder dose of 39 Gy or 36 Gy showed increased urination frequency and enhanced bladder pressure resistance during the whole follow-up time of 100 weeks, compared with the sham-irradiated controls. At half bladder irradiation, only the highest doses (39 Gy to the cranial part of the bladder and 39 Gy or 36 Gy to the caudal part) gave rise to a slight increase in frequency at about 20 weeks after exposure.

Animals↗
PubMed1991

Influence of gastrin, gastrin receptor blockers, epidermal growth factor, and difluoromethylornithine on the growth and the activity of ornithine decarboxylase of colonic carcinoma cells.

Polyamines are essential factors of cell growth and differentiation. Modulation of the cellular polyamine content by 2-difluoromethylornithine (DFMO) inhibiting ornithine decarboxylase (ODC), or by hormones inducing ODC, influences cell growth. Gastrin acts trophically on some colonic carcinomas and their growth is inhibited by gastrin receptor blockers. The mechanism of the trophic action of gastrin on colonic carcinomas is not known. In this study the effect of gastrin, gastrin receptor blockers, epidermal growth factor (EGF) and DFMO on growth and ODC activity of four human colon carcinoma cell lines (SW 403, SW 1116, LS 174 T and Lovo) was investigated. Growth and ODC activity of all cell lines were inhibited by DFMO. Growth of the SW 403 cell line was increased by gastrin and inhibited by the gastrin receptor blocker benzotrypte. The other cell lines did not respond to gastrin and the gastrin receptor blocker. In SW 403 cells ODC activity was increased by gastrin, and was also elevated after treatment with the gastrin receptor blocker. These in vitro results were confirmed by studies on tumours that developed from SW 403 cells in nude mice. Combination of benzotrypte and DFMO did not enhance the antiproliferative effect. EGF increased growth of SW 403 cells, but no induction of ODC activity was measured. LS 174 T cells were not stimulated by EGF. Medium replacement was the strongest stimulus of ODC activity in SW 403 cells already inducing ODC after 3 h. During cell culture ODC activity was high after seeding and decreased continuously with increasing cell density. These data suggest that gastrin induces ODC in gastrin-sensitive colonic carcinoma cells. DFMO appears to be a valuable antiproliferative agent in colonic carcinoma cells.

Animals↗
PubMed1991

Colon adenocarcinomas in European hamsters after application of N-nitroso-bis 2-oxypropyl-amine.

In the European hamster (EH) weekly subcutaneous (s.c.) injections of N-nitrosobis-(2-oxypropyl)-amine (BOP) (LD50, males: 174 mg/kg, body weight (b.w.), females: 118 mg/kg b.w.) induced adenocarcinomas of the colon in 77% (1/10 LD50), 70% (1/20 LD50) and 87% (1/40 LD50) of the treated animals (combined incidence for both sexes (c.i.)). Cholangiocellular carcinomas, the second most common type of tumor were produced in a dose-dependent manner. Furthermore tumors were found in the respiratory tract, urinary tract the integumentum system and the exocrine pancreas. The presented data show a difference between the BOP-induced tumor spectrum in European hamsters and that of Syrian hamsters [5,8,11]. The high incidence of colon adenocarcinomas may provide a further model of colon carcinogenesis.

Adenocarcinoma↗
PubMed1990

In situ distribution of transforming growth factor alpha in normal human tissues and in malignant tumours of the ovary.

The distribution of transforming growth factor alpha (TGF-alpha) in human normal tissues from the uterus, Fallopian tube, ovary, small and large intestine, lung, spleen, kidney, and skin was studied by immunohistochemistry. TGF-alpha was found in epidermis, bronchial epithelium, intestinal mucosa, renal tubules, endo- as well as in exocervical and endometrial epithelium, and in the serous epithelium of the Fallopian tube. No TGF-alpha was detected in the stromal components of any of the tissues nor in any of the pre- and post-menopausal ovaries studied. Twenty-nine ovarian tumours including 23 ovarian carcinomas, one malignant mixed Mullerian tumour, two ovarian metastases of gastrointestinal carcinomas, one dysgerminoma, one sarcoma, and one fibroma were studied for TGF-alpha by the same immunohistochemical method. In 25 cases, specific cytoplasmic staining for TGF-alpha of epithelial tumour cells could be demonstrated. The pattern and intensity of the TGF-alpha immunostain varied among the TGF-alpha-positive tumours. No TGF-alpha was found by immunohistochemistry in the remaining four cases nor in the stromal tumour components of any of the lesions studied. Northern blot analysis for TGF-alpha mRNA was performed on 12 of the tumours. While the immunohistochemistry and blotting results correlated well in ten cases, discordant results were obtained in two lesions.

Blotting, Northern↗
PubMed1990

Enhanced tumor susceptibility of immunocompetent mice infected with lymphocytic choriomeningitis virus.

Mice infected i.v. with high doses of lymphocytic choriomeningitis virus (LCMV; 10(5)-10(6) plaque-forming units) 8-10 days prior to challenge with the methylcholanthrene-induced fibrosarcoma tumor cell line MC57G or the melanoma cell line B16 tumor cells showed an enhanced tumor susceptibility with respect to both growth kinetics of the tumor and the minimal dose necessary for tumor take. After transient initial growth, MC57G tumor cells were all rejected by uninfected C57BL/6 mice by day 14. Mice preinfected i.v. with LCMV 3 weeks before or at the time of tumor challenge, but not those infected 2 months before or 7 days after, showed increasing tumor growth, the tumor take being 100% for 10(6), 50% for 10(5) and 37% for 10(4) MC57G tumor cells injected into the footpad compared with resistance to 10(6) cells in normal mice. B16 melanoma cells also grew more rapidly in LCMV-preinfected mice and by day 40 tumors were established with about 100 times fewer cells, i.e. about 10(3) compared with 3 x 10(4)-3 x 10(5) for uninfected mice. Analysis of the growth of tumor cells in normal and in LCMV-carrier mice revealed that the latter mice were not more susceptible to LCMV-infected than to uninfected MC57G. Since LCMV-carrier mice fail to mount LCMV-specific T cell responses, these results suggest that anti-LCMV-specific T cells may be responsible for acquired immunodeficiency hampering immune surveillance against the tumors studied.

Animals↗
PubMed1990

The relation of amyloidosis to social stress induced by crowding in the Syrian hamster (Mesocricetus auratus).

The aim of the presented study was the investigation of a probable influence of social stress on spontaneous amyloidosis. As stress-inducing parameter crowding of the animals was used. 220 Syrian hamsters were kept individually (controls) or with 3, 5, 7 animals per cage. The crowded animals showed a significant decrease in mean survival time. This was linked to a histopathological examined significant increase in the extent and incidence of amyloidosis in several organs of both male and female hamsters. The kidneys and adrenals were most affected. Chronic inflammation as one probable amyloidosis-inducing factor, was not related to the observed morphological alterations. Furthermore the increase of amyloidosis was statistically not connected with an age-dependent development of amyloidosis. Amyloidosis in Syrian hamsters may be not a mere phenomenon of aging and age-related decline of the immune system but rather the results of a complex set of variables, including factors of social environment and social interactions that continuously put stress on the hamsters.

Amyloidosis↗
PubMed1990

Regulation of the level of the oncoprotein p53 in non-transformed and transformed cells.

In order to contribute to the understanding of the activation of the oncoprotein p53 we determined the metabolic stability of p53 in a variety of non-transformed, immortalized and SV40- and non-SV40-transformed cell lines. In addition, we analyzed the metabolic stability of the SV40 large T antigen in SV40 transformed cell lines. Pulse-chase experiments revealed a low stability (t1/2 = 20 min) of p53 in non-transformed cells and in cells immortalized by the p53 construct pLTRp53cG9. In cells transformed by an activated ras oncogene and pLTRp53cG9 and in methylcholanthrene induced mouse sarcoma cells p53 proved to be progressively more stable with half-lives ranging from 5.5 h to 7 h. Sequential immunoprecipitation with p53- or T antigen specific monoclonal antibodies allowed us to separate T-p53 complexes, uncomplexed p53 and free T antigen in cell extracts from cells transformed by SV40 and pLTRp53cG9. In these transformed cells uncomplexed p53 showed an increased stability (t1/2 = 2.8 h) when compared to p53 from non-transformed cells. Complex formation with T antigen resulted in an additional stabilization of p53 (t1/2 = 13.3 h). Furthermore, T-p53 complex formation also seems to increase the stability of T antigen nearly sixfold. In transformed cells two immunological variants of p53, a PAb246 precipitable and a non-precipitable form showed distinctly different stabilities, indicating a correlation between the ability of p53 subclasses to bind hsc70 protein and their metabolic stability. Moreover, binding to hsc70 correlated with the stabilization of T antigen in CTM cells also where the mutant T antigen is localized exclusively in the cytoplasm. In abortively infected cells p53, even in complex with T antigen, exhibited a relatively low stability (t1/2 = 87 min) indicating that complex formation per se is not sufficient for fully stabilizing p53.

Animals↗
PubMed1989

[Incidence of oro-gastrointestinal mycoses--results of an Ampho-Moronal study].

This report is a survey of epidemiological facts about oro-gastro-intestinal tract mycoses. It is documented that children and older people suffer more often from oro-gastro-intestinal tract mycoses than the rest of the average population. In addition older patients with oro-gastro-intestinal tract mycoses show predisposing factors more frequently than younger people.

Adolescent↗
PubMed1989

Effects of treatment with IL-2 receptor specific monoclonal antibody in mice. Inhibition of cytotoxic T cell responses but not of T help.

Contribution of IL-2R-bearing activated lymphocytes to antiviral host defense was investigated in C57BL/6 mice by treatment in vivo with IL-2R-specific mAb PC61. When treated on days 0 and 1 with respect to infection with either vaccinia virus, lymphocytic choriomeningitis (LCM) virus (LCMV) or vesicular stomatitis virus, 6-day immune mice had low numbers of CD8+ T cells that were reduced to about 10% of the values found for infected but otherwise untreated controls. In contrast, the number of CD4+ T cells was within normal ranges. Correspondingly, induction of strictly T help-dependent antiviral neutralizing IgG antibody titers remained unaffected by the mAb treatment, whereas generation of antiviral cytotoxic T cell activity was abrogated. Anti-IL-2R treatment of thymectomized mice 14 and 15 days after infection prevented generation of secondary antiviral cytotoxic T cells in restimulation cultures in vitro initiated 24 days later. Treatment with IL-2R-specific mAb was comparable to treatment with CD8-specific mAb in preventing mice to eliminate virus. Because of the involvement of antiviral cytotoxic T cells in disease manifestations, treatment with IL-2R-specific mAb protected mice from lethal LCM after intracerebral infection with LCMV and inhibited the footpad swelling reaction caused by local infection with the same virus.

Animals↗
PubMed1989

The occurrence of epidermal growth factor receptors and the characterization of EGF-like factors in human ovarian, endometrial, cervical and breast cancer. EGF receptors and factors in gynecological carcinomas.

In this study we investigated the presence of epidermal growth factor receptors (EGF-R) and the tissue levels of EGF-like factors (EGF-F) in ovarian, endometrial, cervical and breast carcinomas. EGF-R were found in 33/40 (83%) cervical, 15/26 (58%) endometrial, 64/141 (45%) ovarian, and 19/59 (33%) breast carcinomas. The highest number of EGF-R binding sites was detected in cervical carcinomas followed by endometrial, breast and ovarian carcinomas. The tissue concentrations of EGF-like factors, were investigated in extracts of 63 ovarian, 25 breast, 12 cervical, 14 endometrial carcinomas and in 21 biopsies of nonmalignant tissue such as myometrium and ovaries. The extracts of nonmalignant tissues had a mean EGF-F level of 1.5 +/- 0.7 ng/mg with a concentration range from 0 to 4 ng/mg. The mean EGF-F levels of malignant tissues were: ovarian carcinomas 4.2 +/- 1.5 ng/mg (range 0-15 ng), endometrial carcinomas 4.5 +/- 1.7 ng/mg (range 0-12 ng), cervical carcinomas 4.15 +/- 1.1 ng/mg (range 0-8) and breast carcinomas 3.16 +/- 1.1 ng/mg (range 0-10 ng). About 30% ovarian, endometrial and cervical carcinomas and 16% breast carcinomas, respectively, had enhanced EGF levels from 5 ng/mg to 15 ng/mg compared to nonmalignant tissues. The EGF-F of tissue extracts consists of EGF and transforming growth factor TGF alpha) as shown by the results of EGF and TGF alpha radioimmunoassays. It is assumed that in some tumors the EGF-F tissue levels influence the number of biochemically detectable EGF binding sites.

Binding Sites↗
PubMed1989

Human ovarian carcinomas: correlation of malignancy and survival with the expression of epidermal growth factor receptors (EGF-R) and EGF-like factors (EGF-F).

We have studied the concentration of epidermal growth factor receptors (EGF-R) in 115 different malignant ovarian tumors (101 ovarian carcinomas) and EGF-like factors (EGF-F) in tissue extracts of 63 different ovarian carcinomas and 20 non-malignant tissues. 36% of ovarian carcinomas are EGF-R positive. The calculated mean EGF-F level of 4.2 +/- 1.5 ng mg-1 (range: 0-15 ng mg-1) in ovarian carcinomas is significantly enhanced compared to 1.5 +/- 0.7 ng mg-1 (range: 0-4 ng mg-1) of non-malignant tissue extracts. The correlation between EGF-R positive as well as negative ovarian carcinomas and the results of a primary chemotherapy of advanced ovarian carcinomas (n = 92) revealed a significantly higher remission rate of EGF-R positive tumors (66%) compared to EGF-R negative cases (23%). 84% of tumors with progressive disease were EGF-R negative. The mean EGF-F levels were calculated for prognostic subgroups of ovarian carcinomas. Increased EGF-F levels are significantly associated with progressive disease compared to all patients or the remission group. 15/16 cases with EGF-F levels greater than 5 ng mg-1 showed progressive disease. The overall survival time of patients with tumor tissue EGF-F levels greater than 3.5 ng mg-1 was worse than that of patients with low EGF-F levels. Multivariate analysis showed that the EGF-F level was, after grading, the second most important factor for predicting overall survival.

Epidermal Growth Factor↗