PubMed Health⌕ Search

Biomedical subjects

J Rüschoff

Publications and source records attributed to J Rüschoff.

At least 73 records · Page 4Linked to original sources
PubMed1996

Prognostic significance of molecular biological and immunohistological parameters in gastrointestinal carcinomas.

Histological type, malignancy grade, and tumor stage are among the most important parameters predicting outcome in cancer patients. Making use of immunocytochemistry as well as polymerase chain reaction-based techniques the demonstration of micrometastatic tumor spread, for example, into bone marrow, lymph nodes, and peritoneal cavity, is a new staging parameter of prognostic significance. In contrast, the prognostic value of different proliferation markers such as Ki67 (Mib 1), PCNA, and AgNOR has not yet been unequivocally established. A series of genetic change has been described in the development of cancer. In general, these changes seem to be of predictive value within defined tumor stages and it might be helpful to determine several genetic lesions within one tumor. Very recently a new mechanism of carcinogenesis closely related to the hereditary nonpolyposis cancer syndrome (HNPCC) was detected. Due to mutations in mismatch repair genes (hMSH 2, hMLH1, hPMS1,2) instabilities in simple repetitive genomic sequences occur, which are the genetic hallmark of most HNPCC tumors. This opens a new field to cancer prevention.

Animals↗
PubMed1996

[Benign placental trophoblast nodule. Case report with overview of proliferative diseases of the intermediate stage trophoblast].

This report reviews proliferative diseases of intermediate trophoblast cells and summarises clinical findings and pathohistological and immunohistochemical features of a placental site nodule. This recently described entity is an endometrial or endocervical benign proliferation of intermediate trophoblast cells occurring after intrauterine gestation. Patients usually present with a history of abnormal vaginal bleeding and frequently cells that are present in their cervical smears are misinterpreted as squamous dysplasia. In such cases it is important to distinguish the placental site nodule from squamous lesions or decidual polyps; this is possible by means of immunohistochemistry.

Adult↗
PubMed1996

Tumor necrosis factor effects on ascites formation in an experimental tumor model.

In humans, treatment of malignant ascites with bolus TNF leads to resolution of the ascites. In an experimental model NMRI nude mice were inoculated intraperitoneally with human NIH-OVCAR3 adenocarcinoma cells, resulting in production of ascites and intraperitoneal tumor growth. Ascites formation and tumor growth after IP injection of recombinant human TNF was determined. Depending on the treatment schedule, a dual effect of TNF on the development of ascites was seen. Doses of TNF (1-10 micrograms/g) given once per week completely prevented ascites production, whereas the same doses of TNF given on a daily schedule induced enhanced ascites formation in an inverse TNF dose relationship. The area of tumor cell-covered peritoneal lining corresponded to these findings, indicating a correlation of tumor mass with ascites production. In an attempt to prevent renewal of ascites after drainage, neither inhibition nor enhancement in ascites production was seen when TNF was given five times per week. However, doses of 10 micrograms/g of TNF once per week led to almost complete inhibition of ascites reappearance. Histological examination of animals that received repeated TNF treatment demonstrated chronic peritonitis with strong stromal proliferation, angiogenesis, and increased adhesion of tumor cells to the peritoneum.

Animals↗
PubMed1996

Expression of proliferating cell nuclear antigen (PCNA) and Ki-67 in dysplasia in inflammatory bowel disease.

OBJECTIVE: Previous studies have revealed large variations in the interobserver agreement of dysplasia grading in inflammatory bowel disease. Therefore, we investigated the diagnostic value of two novel monoclonal antibodies (MIB 1 against Ki-67 and PC 10 against PCNA) in the detection of dysplasia. METHODS: A total of 62 biopsies were investigated and histologically classified as follows: 13 probably positive for dysplasia; 15 low-grade dysplasia; five high-grade dysplasia; and 15 inflammation without dysplasia and 14 normal controls. The percentage of positive Ki-67- or PCNA-stained nuclei (= labelling index) was determined in relation to the distribution throughout the mucosa. RESULTS: In all biopsies PCNA-labelling index exceeded that of Ki-67-labelling index. In the superficial half of the crypt PCNA- and Ki-67-labelling indices in the biopsies with 'indefinite for dysplasia, probably positive' or low-grade dysplasia exceeded that of normal tissue (P < 0.001). However, an unequivocal discrimination between biopsies with 'indefinite for dysplasia, probably positive' or low-grade dysplasia and inflammation was not possible. PCNA- and Ki-67-labelling indices were significantly higher in high-grade than in low-grade dysplasia (PCNA 81.4% vs. 44.3%, Ki-67 54.8% vs 30.9%, P < 0.001). Most interestingly, labelling indices of both markers were significantly (P < 0.0001) higher in biopsies with high-grade dysplasia than with active inflammation in the superficial half of the crypt. CONCLUSION: PCNA and Ki-67 are useful adjuncts in the diagnosis of high-grade dysplasia, because high-grade dysplasia can easily be distinguished from low-grade dysplasia or active inflammation if the distribution of the positive-stained cells within the mucosa is taken into account. Lower unspecific binding and lower influence on proliferation activity by inflammation prompts us to prefer Ki-67 (MIB 1).

Biopsy↗
PubMed1996

Nonradioactive arbitrarily primed polymerase chain reaction: a novel technique for detecting genetic defects in skin tumors.

Initiation and progression of melanocytic and non-melanocytic skin tumors are accompanied and probably caused by a variety of genetic defects. In contrast to other human tumors, however, limited amounts of available tissue in skin cancer often hamper extensive genetic studies of native material of early lesions. Therefore, we applied a novel DNA fingerprinting technique based on polymerase chain reaction (PCR), the arbitrarily primed PCR (AP-PCR). This technique enabled us to scan large parts of the genome (about 30 kb/PCR reaction) for somatic mutations starting with minute amounts of tissue. In contrast to previous reports on AP-PCR, we were able to visualize PCR products by a rapid nonradioactive silver-staining technique using a simple device for staining of large polyacrylamide gels. In nine benign and malignant melanocytic skin tumors, the method provided a set of reproducible DNA fingerprints. Genetic defects were detected by comparing the fingerprints of tumor cells and constitutive DNA from blood leukocytes. Since nonradioactive AP-PCR fingerprinting also offers the unique capability to isolate and sequence polymorphic DNA fragments from fingerprint gels, we conclude that this technique seems to be important and practically feasible for elucidating the genetic roots of skin tumors.

Base Sequence↗
PubMed1996

[Asymptomatic endocarditis? Are consequent histological studies useful in valve surgery?].

After aortic valve replacement for endocarditis, follow-up treatment with antibiotics is imperative. However, the question of how reliable preoperative and intraoperative diagnosis of endocarditis is in cases involving aortic defects is unclear. Of the 187 patients who underwent aortic valve replacement with or without coronary bypass surgery between June 1992 and June 1994, 150 exhibited no indications of endocarditis during preoperative and intraoperative examinations. In 17 cases (Group A) histological findings indicated acute florid endocarditis in 7 patients and chronic lymphocytic endocarditis in 10. Contrarily, histological examinations of 133 patients (Group B) revealed myxoid and/or sclerotic valve degeneration. WBC and LDH activity, examined one day preoperatively and on the first and second days postoperatively, exhibited no significant differences between the two groups, with the exception of LDH activity on the first postoperative day (Group A: 490 +/- 114, Group B: 403 +/- 132, p = 0.04). Of the clinically asymptomatic patients requiring aortic valve replacement, 11.3% exhibited acute florid endocarditis upon histologic examinations. This subgroup cannot be identified based upon routine preoperative or postoperative laboratory tests or intraoperative observation. Histological examination of the aortic valve is useful for identifying the high percentage of otherwise nonidentifiable endocarditis. Further study will be required to determine therapeutic recommendations based upon such diagnosis.

Adult↗
PubMed1996

[Microsatellite instability--a new aspects in genetics and molecular biology of hereditary nonpolyposis and sporadic colorectal tumors].

Microsatellite instability (or replication error phenotyp) is a new molecular phenotyp of a substantial fraction of human cancers. The microsatellite instability in these cancers arises from alterations in normal regions of the genome consisting short sequences of repeated DNA. Ubiquitous changes in length of microsatellite sequences between constitutional and tumor DNA occur in about 90% of cases of HNPCC and in about 15% of cases of non-familial, sporadic colorectal cancer. Microsatellite instability is also found in a substantial percentage of sporadic endometrial, and gastric cancer, as well as in additional sporadic cancers, such as lung cancer which is usually not associated with HNPCC. Thus far, four different mismatch repair genes (hPMS1, hPMS2, hMLH1 hMSH2), all homologous to bacterial DNA repair genes have been identified as involved in HNPCC kindreds, and consequently they are associated with microsatellite instability. In conclusion, these basic genetic informations provide new insights into a new molecular pathway in oncogenesis, i.e. the occurrence of mutations in genomic stability genes leading to an increased cellular mutation rate (replication error phenotyp) and thus to cancer.

Cell Transformation, Neoplastic↗
PubMed1995

Comparative genomic in situ hybridization of colon carcinomas with replication error.

The aim of the present study was to detect complex genetic alterations in colorectal carcinomas with and without microsatellite instability (MIN) by comparative genomic in situ hybridization. MIN due to replication errors is the hallmark of hereditary nonpolyposis colon cancer. None of 6 MIN-positive tumors showed amplifications, and only 2 tumors displayed deletions of one chromosomal segment each. In contrast, different gains and losses were observed in 11 of 12 MIN-negative carcinomas. The most frequent gains affected chromosomes 7, 13, and 20q, whereas deletions were observed on chromosomes 17, 18, and 9p. These results demonstrate different mechanisms of genetic instability in subgroups of colorectal carcinomas and may, therefore, support the hypothesis of different etiologies in tumors with and without MIN.

Adult↗
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↗