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J Rüschoff

Publications and source records attributed to J Rüschoff.

At least 19 recordsLinked to original sources
PubMed1995

Promotion of experimental liver metastasis by tumor necrosis factor.

Models for experimental metastasis were established to investigate the influence of rmTNF on tumor-colony formation in the liver. Highly metastatic lymphoma tumor cells were either injected i.v. or inoculated s.c. to form spontaneous metastases. In both systems, administration of rmTNF to the animals led to significant enhancement of the number of liver metastases in comparison with control groups. The number of metastatic tumor-cell colonies at an early stage of metastasis was increased, as well as the number of surface metastases in a late stage. Consequently, TNF-treated animals revealed a higher mortality. The optimal time for TNF to exert this metastasis-enhancing effect was found to be 7 days after tumor inoculation. In vitro adhesion of the lymphoma tumor cells to a mouse endothelioma cell line was strongly inhibited by monoclonal antibodies interfering with the interaction of VCAM-1 with VLA-4. These results support and extend earlier results with a fibrosarcoma lung colonization model. In addition, they show that stimulation of the immune system in tumor-bearing hosts activates tumor-promoting pathways, in addition to having possible beneficial effects.

Animals↗
PubMed1995

Microsatellite instability: new aspects in the carcinogenesis of colorectal carcinoma.

Very recently a new molecular mechanism in the tumorigenesis of colorectal carcinoma has been described which is closely linked to hereditary non-polyposis colonic cancer (HNPCC). Ubiquitous changes in the length of simple repetitive DNA sequences between constitutional and tumour DNA occur in about 90% of cases of HNPCC and in about 15% of cases of non-familial, sporadic colorectal carcinoma. Such microsatellite instabilities have been shown to be the phenotypical marker of mutations in the human homologues of prokaryotic mismatch repair genes (MutS, MutL, MutH). These data provide crucial new tools in the detection of patients at high risk of developing colon cancer and other HNPCC-related carcinomas. In addition, these developments provide new insights into a new, presumably primary event in oncogenesis, i.e. the occurrence of mutations in genomic stability genes leading to an increased cellular mutation rate ("mutator phenotype") and thus to cancer.

Carcinogens↗
PubMed1995

Detection of microsatellite instability in human colorectal carcinomas using a non-radioactive PCR-based screening technique.

The aim of the present study was to establish a rapid, non-radioactive screening method for the detection of microsatellite instability (MIN). MIN is the primary characteristic of the mutator phenotype in tumours constituting hereditary non-polyposis colon cancers (HNPCC). We investigated 30 patients suffering from colorectal cancer using a non-radioactive PCR-based technique. MIN was present in 7 of 30 (23%) of the cases. There was a statistically significant correlation between MIN and localization of the tumour. Five of 7 (72%) tumours with MIN but only 4 of 23 (17%) tumours without MIN were localized in the proximal colon (P < 0.01). There was a tendency to higher MIN frequency in tumours of patients with familial clustering of cancers. However, this was statistically not significant (P > 0.05). In addition, no correlation between MIN and tumour grade and stage was found. For the investigations in the present study we used a non-radioactive PCR-based method followed by denaturating polyacrylamide gel electrophoresis and silver staining. This method is highly sensitive and reproducible. Thus, PCR-based analysis using a non-radioactive staining technique represents a comprehensive tool for MIN screening in diagnostic pathology.

Adult↗
PubMed1995

Cell proliferation assessment in oncology.

A review of the current knowledge on cell cycle control and the techniques used to assess proliferation of normal and neoplastic cells was the focus of a workshop in Regensburg, Germany, held under the joint auspices of the Graduiertenkolleg: Therapieforschung Onkologie and the Committee on AgNOR Quantification. An overview of the recently discovered group of cyclins and their specific kinases, and of other proliferation-associated antigens, such as Ki67, PCNA and topoiseromase II alpha, was given. The topics continued with a reappraisal of modern imaging and flow-cytometric techniques. An update of the relation of AgNORs to cellular proliferation and differentiation was the link to presentations on clinical data, problems and strategies for standardization, as well as guidelines to establish the prognostic value of marker molecules. These lectures were supported by posters. Bringing together researchers from life sciences, technically oriented workers, pathologists, and clinicians resulted in a lively and constructive discussion, which is briefly summarized in the Concluding remarks.

Cell Cycle↗
PubMed1995

Correlation of nucleolar organizer regions with secretory and regenerative process in experimental cerulein-induced pancreatitis in the rat.

Silver staining of nucleolar organizer regions (AgNORs) demonstrates loops of DNA that transcribe ribosomal RNA. Their number and size have been attributed to rDNA transcription activity involved in protein synthesis and thus associated with proliferation. The exact relationship among proliferation, protein synthesis, and expression of AgNORs is, however, not yet well established. We therefore investigated AgNORs in an experimental model of cerulein-induced rat pancreatitis. During secretory stimulation with maximal doses of cerulein (0.25 micrograms/kg/h) for 12 h, AgNOR number and size per nucleus as well as 3H-thymidine label index did not change, although there was a marked increase in pancreatic volume flow, up to 150%, and of protein synthesis rate, up to 180% of the control levels. In contrast, after infusion of supramaximal doses of cerulein (5.0 micrograms/kg/h), AgNOR and 3H-thymidine label values rose significantly, with a distinct peak at day 3 after induction of pancreatitis. Most interestingly, AgNOR number and size were elevated 12 h before DNA replication started as determined by 3H-thymidine incorporation. At the same time intracellular protein synthesis proved to be decreased approximately 30-50% compared to controls. Our data confirm that AgNOR is a marker of proliferation that reflects regulatory events in the cell cycle earlier than 3H-thymidine incorporation. Here we demonstrate for the first time that this phenomenon is independent of the total intracellular protein synthesis rate.

Acute Disease↗
PubMed1995

In vitro and ex vivo expression of nucleolar proteins B23 and p120 in benign and malignant epithelial lesions of the prostate.

The expression of two specific nucleolar antigens, p120 and B23, has been investigated in the prostatic carcinoma cell line LNCaP as well as in 40 frozen and 40 formalin-fixed tissue samples of benign and malignant prostatic lesions (15 benign hyperplasias, 5 grade 1, 15 grade 2, and 5 grade 3 carcinomas). In vitro, immunoreactivity of p120 was confined to nucleoli of proliferating cells, with virtually no negative staining during S and G2/M phases. Unlike p120, B23 was expressed in the nucleoli of all LNCaP cells independently of growth and cell cycle phases. Hence, B23 was detectable in all stromal as well as in normal and malignant epithelial prostatic cells, both in fresh and in formalin-fixed tissue sections after microwave treatment. In contrast, the immunoreactivity of p120 was almost completely restricted to the nucleoli of prostate carcinoma cells: frozen sections of benign prostatic hyperplasia (n = 15) were either totally negative for p120 (n = 13) or had a low percentage of positively stained cells (labeling index = 3.3% in 3 cases). In the carcinoma group 76% (19/25) of the specimens were p120 positive, and there was a significant rise of labeling index from 18.1% in grade 1 to 82.2% in grade 3 carcinomas (P < 0.001). In contrast to B23, p120 could not be reliably demonstrated in formalin-fixed and paraffin-embedded tissue. We therefore conclude that anti-B23 is a general marker of nucleoli, whereas expression of p120 appears to correlate with "hyperactivity" of the nucleolus and provides a new tool for flow cytometrical and immunohistochemical assessment of nucleolar activity in tumor pathology.

Adenocarcinoma↗
PubMed1995

[Masked course of Whipple disease with uveitis, infection, endocardial involvement and abdominal lymphomas--case report and review of the literature].

Whipple's disease is a systemic disease which may virtually affect any organ system, but in many cases it involves the small intestine causing gastrointestinal symptoms. The differential diagnosis is difficult since symptoms may be nonspecific. We report the case of a 44-year old white male patient with a history of migrating arthralgia and chronic fatigue. The patient newly developed an uveitis and underwent a vitrectomy; the further clinical work-up including gastroscopy with intestinal biopsy revealed no sufficient diagnosis. Subsequently, the patient's condition deteriorated with marked weight loss, fever and progressive weakness. An anaerobic sepsis with a corynebacterium was confirmed and with i.v.-antibiotics the patients's condition improved markedly. The further examinations disclosed enlarged mesenteric lymph nodes and the involvement of other organs (endocard, liver). CT-guided biopsy only showed fatty degeneration, but operative adenectomy confirmed Whipple's disease. The patient remained without relapse on long-term antibiotic treatment with doxycycline until today. Obviously, in our case the intestinal biopsies failed to detect Whipple's disease after the successful initiation of antibiotic treatment. In the absence of gastrointestinal findings and with concomitant secondary diseases the definitive diagnosis can be difficult. In addition, the previous uveitis and the endocardial involvement are most interesting.

Abdominal Neoplasms↗
PubMed1995

Human alveolar macrophages: comparison of cell size, autofluorescence, and HLA-DR antigen expression in smokers and nonsmokers.

To investigate the influence of cigarette smoking on alveolar macrophages (AM) we compared morphologic and immunocytochemic characteristics of bronchoalveolar lavage cells collected from 10 smokers and 8 nonsmokers. AM were studied using single cell fluorescence photometry. AM of smokers were larger in size (p < 0.001), showed stronger autofluorescence (p < 0.001), and expressed fewer HLA-DR antigens (p < 0.001) compared with AM of nonsmokers. AM of smokers were more heterogeneous in respect to cell size, autofluorescence, and HLA-DR antigen expression. HLA-DR antigen density on AM of smokers was independent of cell size and autofluorescence. This suggests that tobacco smoke reduces HLA-DR antigen expression in AM of different maturational states and that this defective expression of HLA class II antigens is not dependent on the amount of phagocytosed autofluorescent tobacco particles.

Aged↗
PubMed1994

[Value of nucleolus organizer regions (AgNORs) in dermatologic oncology].

Nucleolus-organizing regions (Ag-NORs) are silver-stained loops of DNA transcribing to ribosomal RNA. Quantitative analysis helps to differentiate normal tissue from malignant tissue and can be used for diagnosis in several kinds of tumours. The analysis of AgNORs can also be used in dermatopathology for diagnostic and prognostic purposes. Apart from skin tumours such as basal, cell carcinomas and squamous cell carcinomas, this technique is of interest principally for melanocytic lesions. Benign naevi can be distinguished from malignant melanomas by simple counting of the AgNOR dots. For the differentiation of dysplastic naevi, Spitz naevi and malignant melanomas, this parameter alone is not sufficient. By combination of several AgNOR parameters (number, size, pattern of dispersal) only, significant differentiation could be achieved. The prognostic value of AgNORs remains to be examined.

Basal Cell Carcinoma↗
PubMed1994

Diffuse alveolar damage in the rat lung after short and long term exposure to nitrogen dioxide.

In order to quantify parenchymal, vascular and epithelial changes occurring in the exudative and organizing phase of diffuse alveolar damage (DAD) induced by inhaled NO2 groups of 7 rats were continuously exposed to 5, 10 or 20 ppm NO2 for 3 and 25 days alternatively. AgNOR analysis revealed the highest proliferative activity in the epithelium of the respiratory bronchioles. In this region already after 3d exposure to 5 ppm the maximum AgNOR number was reached. In contrast to long-term exposure after 3d exposure to 5 and 10 ppm NO2 the AgNOR number in the respiratory bronchioles was significantly higher than in central airway epithelia. After long-term exposure to 5 and 10 ppm AgNOR number decreased to normal values or showed no further significant increase, long-term exposure to 20 ppm resulted in a further increase of the AgNOR number. A significant increase of the alveolar circumference and decrease of alveolar surface density was found after an exposure to 20 ppm for 3d and long-term exposure to 10 and 20 ppm NO2, whereas the 5 ppm exposure groups disclosed no significant change of these values. Medial hypertrophy was detected after exposure to 10 and 20 ppm NO2 for 25 days, after the exposure to 5 ppm for 3d and 25d medial thickness was significantly decreased due to vasodilation induced by NO, one of the major reaction products of NO2.

Animals↗
PubMed1994

Torsades de pointes arrhythmia in a patient with left ventricular myxoma.

A 38-year-old woman suffered from syncopes due to torsades de pointes arrhythmias. Echocardiography showed a left ventricular mass that was resected. By immunohistochemical investigations, an organized thrombus was excluded and the diagnosis of a rare ventricular myxoma was confirmed. Postoperatively the arrhythmias resolved without recurrence. We conclude that left ventricular myxoma may cause life-threatening arrhythmias, possibly by irritation of cardiac mechanoreceptors. To our knowledge, this is the first case of a left ventricular myxoma associated with a torsades de pointes arrhythmia.

Adult↗
PubMed1994

Silver staining nucleolar organizer region in prostate cytology.

Amongst males, the prevalence of prostate cancer is third in frequency with a rising incidence. As the population grows older, the number of latent cancer of the prostate increases. Therefore, diagnostic tools for an early detection of this malignancy are necessary. Silver staining of nucleolus organizer regions (AgNOR) is a new technique in tumour analysis. It is especially valuable as an addition to classical prostate cytology. A report on 90 cases of transrectal prostate aspiration biopsies is presented. 81 of these had a histological evaluation (biopsy gun) at the same time. The air-dried slides were stained according to Ploton et al. [10]. The AgNORs were counted and measured by means of an interactive image analysis system. Patients without malignancy were reliably classified as negative both by routine cytology as well as by AgNOR analysis. The sensitivity in routine tumor diagnosis was ca. 87%. In contrast, the AgNOR index revealed a sensitivity of 96% and a specificity of 97%. Thus, AgNOR staining improves differential diagnosis in inconclusive cases. Our data suggests that the inexpensive AgNOR analysis improves differentiation between carcinomatous and benign prostatic cells. It is a useful tool, in addition to routine prostatic cytology.

Biopsy↗
PubMed1994

AgNOR quantification with special reference to staining patterns.

Silver staining of nucleolar organizer regions (AgNORs) is now widely used as a marker of malignancy in tumor pathology. Standardization of the AgNOR technique has thereby been shown to be of central importance. Basically, three types of AgNOR evaluation have been used: the counting method, image analysis and pattern recognition. Today, image analytical determination of AgNOR area per nucleus is considered to be the state of art method of AgNOR evaluation. In contrast, counting of every single AgNOR dot is laborious and less reproducible. For routine purposes, however, a rapid evaluation of AgNORs would be desirable. In order to elucidate the value of AgNOR distribution patterns systematic in vitro studies using four different urothelial cell lines (HU609, RT4, J82, MGHU1) were performed. AgNOR number (NORN) and AgNOR area (NORA) were closely related to the population doubling time (PDT) and increased during transition from G0/G1 to S/G2 cell cycle phase. In addition, both parameters were significantly elevated in the polyploid RT4 cell line. In contrast, number and area of AgNOR cluster (aggregates of at least two AgNOR dots) were less significantly correlated to PDT. Formation of large AgNOR clusters (maximum diameter over 6 microns) was, however, restricted to the well differentiated cell lines (HU609, RT4) although PDT was almost identical in all 4 cell lines at exponential growth phase. Thus, NORN and NORA are not only related to cell proliferation but also to cell cycle phases and ploidy.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Cycle↗
PubMed1993

Gastric argyrophil (enterochromaffin-like), gastrin, and somatostatin cells after proximal selective vagotomy in man.

The number, size, and volume density of endocrine cells was determined in biopsies obtained endoscopically in patients after proximal selective vagotomy (PSV; N = 31), antrectomy (N = 9), untreated duodenal ulcer (DU) disease (N = 11), and in controls (N = 15). Serum gastrin was significantly elevated after PSV (mean 60 pg/ml) compared to DU patients (29 pg/ml), controls (26 pg/ml), and after antrectomy (11 pg/ml). Volume density of fundic argyrophil (largely enterochromaffin-like) cells after PSV (0.74%) and in DU disease (0.63%) were significantly (P < 0.001) higher when compared with controls (0.37%) but lower after antrectomy (0.24%; P < 0.02). The density of argyrophil cells was not influenced by the interval following PSV or the magnitude of hypergastrinemia. Antral gastrin cells were increased after vagotomy, whereas the antral and fundic somatostatin cell numbers were reduced after PSV. It is concluded that: (1) a major role of the vagal nerve as a trophic factor for enterochromaffin-like cells could not be demonstrated after PSV, and (2) moderate hypergastrinemia after PSV did not induce proliferation of ECL cells.

Adult↗
PubMed1993

Diagnostic value of AgNOR staining in follicular cell neoplasms of the thyroid: comparison of evaluation methods and nucleolar features.

The diagnostic value of argyrophil staining of nucleolar organizer regions (AgNOR) was studied in 95 nonneoplastic and neoplastic follicular lesions of the thyroid. Different AgNOR parameters such as number, size, and distribution pattern were determined using digital image analysis. In addition, nuclear and nucleolar size as well as the percentage of nucleoli touching the nuclear membrane (nucleolar margination) were assessed. A stepwise increase in nuclear size and AgNOR counts from normal thyroid tissue to follicular adenoma as well as from differentiated follicular to anaplastic carcinoma was found (mean nuclear area [micron2]/mean AgNOR number per cell: 21.5/1.6 vs. 34.4/3.5 and 45.3/5.0 vs. 66.5/10.8, p < 0.01/p < 0.001). There was, however, no clear separation between these diagnostic groups. In contrast, an almost total discrimination between follicular adenoma and carcinoma was achieved by quantification of AgNORs per tumor cell nucleolus (AgNOR distribution score). In benign adenomas, 3.3% (range, 0-8.8%) of the cells showed nucleoli with at least five AgNOR dots within one focal plane, whereas in follicular carcinomas, the corresponding value was 34.1% (range, 12-75%). Two of four cases of so-called atypical adenomas showed values in the range of benign adenomas, and two were in the range of follicular carcinomas. In comparison with other nuclear and nucleolar parameters, the AgNOR distribution score proved the most valuable diagnostic criterion for the cytomorphological differentiation between follicular adenoma and carcinoma of the thyroid.

Adenocarcinoma, Follicular↗