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J Rüschoff

Publications and source records attributed to J Rüschoff.

At least 55 records · Page 3Linked to original sources
PubMed1998

Macrophage tissue infiltration, clinical symptoms, and signs in patients with lumbar disc herniation. A clinicopathological study on 179 patients.

It is postulated that in addition to nerve-root compression, an inflammatory stimulus of the herniated lumbar disc is responsible for sciatic pain and radiculopathy. The clinical relevance of the histologically described inflammatory infiltrates is, however, not clearly defined [8, 22]. It was the aim of this study to assess the clinical relevance of inflammatory cells in herniated lumbar disc specimens. The presence of inflammatory cells was examined immunohistochemically in routinely processed resection specimens of the lumbar disc. The histological results were compared to prospectively obtained clinical data. Disc specimens of 179 patients who underwent surgery for lumbar disc herniation were studied immunohistologically. Preoperatively each patient received a visual analogue scale for classification of the pain level and general clinical data were recorded prospectively. Varying amounts of inflammatory cells could be demonstrated in the resected disc tissue. In the statistical workup no statistically significant correlation between the histological evidence of macrophage infiltrates and the pain grading scale or the clinical data could be found. In our study there is no statistically significant correlation between macrophage infiltrates in herniated lumbar disc specimen and the obtained clinical data.

Adult↗
PubMed1998

Coexistent thyroiditis is associated with lower tumour stage in thyroid carcinoma.

BACKGROUND: Microsatellite instability (MSI) is a new mechanism described in carcinogenesis of several tumours and seems to predispose for cancer in some chronic inflammatory diseases. As thyroiditis is thought to be both the cause and the consequence of thyroid carcinoma, it was the aim of this retrospective study to investigate the epidemiology and the influence of a coexistent thyroiditis on prognosis and clinicopathological parameters in an iodine-deficient area. METHODS: The grade of lymphocytic infiltration (LI) of 153 thyroid carcinomas was determined in paraffin-embedded tissues: G0 = no LI, G1 = peritumoral LI, G2 = peritumoral LI with follicle, G3 = diffuse LI. A non-radioactive PCR-based screening method was used for detection of MSI. RESULTS: Twenty-seven (17.7%) out of 153 carcinomas were accompanied by thyroiditis (G1, 16; G2, 5; G3, 6). Ten cases fulfilled the criteria necessary for diagnosing Hashimoto's thyroiditis. Nine out of 10 (90%) Hashimoto's cases and 16 out of 17 (94%) other thyroiditis cases were associated with a significantly (chi2 < 0.01) lower pT stage (pT1, pT2) than cases without thyroiditis. No statistical association was found by comparing multifocality or sclerosing variants with the grade of lymphocytic infiltration. MSI was detected neither in patients with severe inflammation nor in the absence of thyroiditis. CONCLUSIONS: MSI does not seem to play a role in the pathogenesis of thyroid carcinoma. Coexistent thyroiditis is associated with a lower pT stage and thus could be an indicator of a better prognosis.

Adult↗
PubMed1998

Detection of dysplastic lesions by fluorescence in a model of colitis in rats after previous photosensitization with 5-aminolaevulinic acid.

BACKGROUND AND STUDY AIMS: Endoscopic diagnosis of dysplastic lesions and early cancers in chronic ulcerative colitis is a major problem. Identification of suspicious lesions is influenced by the macroscopic appearance of the colon, but also by the endoscopist's experience. In this study we evaluated the identification of dysplastic lesions by the naked eye in an animal model of colitis after 5-aminoaevulinic acid-induced photosensitization. METHODS: 80 male Wistar rats were examined. Acute and chronic colitis were induced by oral application of 5% dextrane sulfate sodium (DSS) in 1-7 cycles (1 cycle = seven days DSS and 10 days water). For sensitisation 5-aminolaevulinic acid (5-ALA) at different doses (0, 10, 25, 50, 75, 100, and 200 mg/kg) was used. The colonic fluorescence was examined under a blue light (390-436 nm) for excitation. Histological findings of fluorescent and non-fluorescent biopsy specimens were recorded. RESULTS: Using 100 mg/kg 5-ALA intravenously for photosensitization, all dysplastic lesions (5/5) showed fluorescence (sensitivity 100%). However, at this concentration of 5-ALA, 60 false positive lesions were found out of 76 specimens taken from lesions that were not dysplastic--only 16 specimens of non-dysplastic lesions did not fluoresce (specificity 21%). Using 75 and 50 mg/kg 5-ALA intravenously sensitivity decreased to 92% (36/39) and 42% (5/12), respectively, while specificity increased to 35% (29/82) and 62% (45/73). Using 50 mg/kg 5-ALA intravenously, fluorescence-positive biopsy specimens showed inflammation of the colon in 31% whereas only 12% contained normal mucosa (p < 0.01). The distribution of fluorescence-positive biopsy specimens with histologically confirmed inflammation was similar for different grades of inflammation after sensitisation with 75 and 100 mg/kg 5-ALA, whereas with 50 mg/kg 5-ALA fluorescence-positive biopsy specimens contained significantly (p < 0.05) more moderate, massive, or ulcerative inflammation (79%) than mild inflammation (21%). CONCLUSION: 5-ALA induced photosensitization gave a high sensitivity, but low specificity in identifying dysplastic lesions in DSS-induced colitis in rats. In this animal model inflammation is a major factor in disturbing the fluorescence localisation of dysplasia after sensitisation with 5-ALA.

Acute Disease↗
PubMed1998

Late onset primary oxalosis type I: an uncommon presentation of a rare disease.

A 46-year-old woman developed rapidly worsening renal insufficiency. Extensive calcification of the kidneys was found. The patient also suffered from ischaemic neuropathy, myopathy and arthritis. In a muscle biopsy multiple calcium oxalate crystals could be demonstrated surrounded by inflammatory infiltrates. Levels of oxalate in serum were markedly elevated. Diagnosis of primary hyperoxaluria type I was made by measuring alanine/glyoxylate aminotransferase activity in a liver biopsy. The patient underwent kidney transplantation twice, but each of the transplants failed after a very short time owing to hyperacute rejection and rupture of the organ, respectively. Eventually, combined liver/kidney transplantation was successfully performed. Two years after the transplantation, both organs work with good function. This case of primary hyperoxaluria type I is remarkable for the late onset of symptoms and the extensive involvement of other organ systems in addition to the kidneys. This case presentation confirms previous reports discouraging isolated kidney transplantation for patients with primary hyperoxaluria. Only combined liver/kidney transplantation can correct the metabolic defect and may give these patients superior long-term benefit.

Female↗
PubMed1998

[Molecular diagnosis and clinical consequences in families with HNPCC syndrome].

Thirteen families were included in our HNPCC surveillance program, eight of which met strict and three incomplete Amsterdam criteria. Two index patients were younger than 35 years of age. Tumors of all index persons showed microsatellite instabilities in at least 50% of the ten markers studied. Immunohistochemical analysis of tumor sections was performed using antibodies against hMLH1 and hMSH2 proteins in order to identify the mutated gene, which is not expressed in the tumor. Coding regions of hMLH1 and hMSH2 genes were amplified by PCR from genomic DNA and sequenced. In nine families pathogenetic mutations all resulting in a truncated protein, could be identified. Furthermore, 21 intron and exon polymorphisms were found. Since July 1997 we have offered surgical and genetic counseling to families with hereditary cancer syndromes in a special outpatient clinic. In addition to 13 index patients three asymptomatic gene carriers were included and eight noncarriers were excluded from the HNPCC surveillance program, as recommended by the HNPCC study group of Germany. Molecular diagnosis has considerable clinical implication in hereditary nonpolyposis colorectal cancer (HNPCC) families with respect to family members who actually have the disease as well as gene carriers and noncarriers.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Prognostic value and clinicopathological profile of microsatellite instability in gastric cancer.

In this study, microsatellite instability (MI) was investigated in 126 gastric carcinomas and correlated with clinicopathological features and prognosis; at least 5-10 microsatellite loci were analyzed. MI was identified in 56 (44.5%) of all investigated carcinomas, one locus being affected in 40 (31.7%) carcinomas, two loci being affected in 6 (4.8%) carcinomas, and more than two loci being affected in 10 (8.0%) carcinomas. MI was correlated with neither age and sex of the patients nor with depth of invasion, lymph node metastasis, tumor differentiation, or histological type according to WHO and Laurén classification. The frequency of MI was the same in early gastric carcinomas as it was in advanced gastric carcinomas, suggesting that MI arises early during the tumorigenesis of gastric cancer. No significant differences in survival could be demonstrated between patients with MI-negative and MI-positive gastric carcinomas.

Adult↗
PubMed1997

Microsatellite instability analysis: a multicenter study for reliability and quality control.

The molecular biology section of the Hereditary Non-Polyposis Colorectal Cancer study group-Germany, instituted a multicenter study to test the reliability and quality of microsatellite instability (MSI) analysis. Eight laboratories compared MSI analyses performed on 10 matched pairs of normal and tumor DNA from patients with colorectal carcinomas. A variety of techniques were applied to the detection of microsatellite changes: (a) silver and ethidium bromide staining of polyacrylamide gels; (b) radioactive labeling; and (c) automated fluorescence detection. The identification of highly unstable tumors and tumors without MSI was achieved in high concordance. However, the interpretation of the band patterns resulted in divergent classifications at several microsatellite marker loci for a large fraction of this tumor/normal panel. The data on more than 30 primers per case suggest that the enlargement of the microsatellite panel to more than 10 loci does not influence the results. In this study, cases with MSI in less than 10% of loci were classified as microsatellite stable, whereas MSI was diagnosed in cases with more than 40% of all markers unstable. We propose that a panel of five microsatellite loci consisting of repeats with different lengths should be analyzed in an initial analysis. When less than two marker loci display shifts in the microsatellite bands from tumor DNA, the panel should be enlarged to include an additional set of five marker loci. The number of marker loci analyzed as well as the number of unstable marker loci found should always be identified. These criteria should result in reports of MSI that are more comparable between studies.

Chromosome Deletion↗
PubMed1997

Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression.

Alterations of the length of simple repetitive genomic sequences (microsatellite instability, MSI) characterize a distinct mechanism of colorectal carcinogenesis. Such MSI has been found to be associated with hereditary nonpolyposis colorectal cancer (HNPCC) that involves mutation of the human mismatch repair genes hMSH2 and hMLH1 as well as many sporadic cancers of most tissue types. Although the study of MSI status is a useful tool for HNPCC screening and for the determination of tumor prognosis in sporadic cases of colorectal cancer, the reliability of MSI diagnosis is still a subject of debate. Here we have examined 58 primary colorectal tumors (selected from a cohort of 200) using 31 microsatellite markers that comprised the most frequent simple repeat types. The expression of the hMSH2 and hMLH1 mismatch repair proteins was studied by immunohistochemistry, and most patients were surveyed for at least 2 years. Reproducibility of gel interpretation, as well as diagnostic sensitivity and specificity of the MSI status, were determined. We found that unambiguous determination of band shifts as well as MSI diagnosis were closely related to the type of the marker repeat and that MSI could be subdivided into "high" MSI (>20% unstable loci), "low" MSI (<10% unstable loci), and microsatellite stable (0% unstable loci). One-half of the patients with high MSI tumors (n = 8) fulfilled either the Amsterdam criteria (n = 4), had at least one relative with HNPCC-related carcinoma (n = 2), or were diagnosed with colorectal cancer at an age below 45 years (n = 2). Fourteen of the 15 high MSI tumors had lost either hMSH2 (n = 8) or hMLH1 (n = 6) protein expression. In contrast, all of the low MSI tumors and the MSI-negative tumors displayed normal expression of hMSH2 and hMLH1. These studies provide a clear recommendation for the uniform use of a panel of 10 microsatellites and a definition of at least 40% instability (using these defined marker loci) in the diagnostic analysis of MSI.

Adenocarcinoma↗
PubMed1997

Comparative analysis of AP-2 alpha and AP-2 beta gene expression during murine embryogenesis.

Transcription factor AP-2 has been identified as playing important roles during embryonic development of the neural tube, neural crest derivatives, skin, and urogenital tissues. Recently, we isolated a second AP-2 transcription factor, AP-2 beta, which is 76% homologous to the previously known AP-2 alpha gene, and showed that both genes are coexpressed in murine embryos at day 13.5 and 15.5 post coitum (pc). In the current study, we used specific cRNA probes to study comparatively AP-2 alpha and AP-2 beta expression by in situ hybridization of murine embryonic tissue sections. Our results reveal that expression of both genes starts at day 8 pc in the lateral head mesenchyme and extraembryonic trophoblast. The expression pattern was identical until day 10 pc but diverged significantly during later stages of development. From day 11 forward, specific expression patterns of AP-2 alpha and AP-2 beta mRNA were observed. Specific AP-2 beta signals were detected in the midbrain, sympathetic ganglia, adrenal medulla, and cornea. Specific AP-2 alpha signals were present in the limb buds, dorsal root ganglia, tooth germs, and Moll's and Meibom's glands. In contrast, expression of both genes occurred in skin, facial mesenchyme, spinal cord, cerebellum, and renal tubular epithelia. Our results indicate that both genes are expressed with different temporal and spatial patterns during embryonic development.

Animals↗
PubMed1997

Effect of ursodeoxycholic acid on the inflammatory activity of indomethacin-induced intestinal inflammation in rats.

The beneficial effects of ursodeoxycholic acid (UDCA) in primary biliary cirrhosis are supposed to be mediated in part by immunological mechanisms. In this study, we have tested whether ursodeoxycholic acid also ameliorates intestinal inflammation induced by indomethacin in rats. Intestinal inflammation was induced in rats by two injections of indomethacin (7.5 mg/kg body weight) 24 h apart. To study its effects on acute inflammation, UDCA (10 mg/kg body weight) was given for three days starting with the first administration of indomethacin; for effects on chronic inflammation, UDCA was given 24 h after the first indomethacin injection for eight days. Rats were sacrificed at days 3 and 9, respectively. In acute inflammation a significant decrease of intestinal injury was observed with UDCA treatment (macroscopic score: 3.00 +/- 0.83 vs. 6.55 +/- 0.53 in controls; p < 0.01; microscopic score: 1.66 +/- 0.28 vs. 2.89 +/- 0.35 in controls; p < 0.05). In chronic inflammation the effects of UDCA treatment were less marked due to a general decline in intestinal injury. Nevertheless a significant decrease in the macroscopic injury score (3.67 +/- 0.62 vs. 1.55 +/- 0.29 in UDCA treated rats; p < 0.01) was observed. Also, there was a significant increase in body weight of UDCA treated rats after nine days compared to controls (28.8% vs. 16% increased body weight in controls; p < 0.01). Thus, ursodeoxycholic acid attenuates the severity of acute damage of small bowel and the development of chronic intestinal inflammation induced by indomethacin in rats.

Acute Disease↗
PubMed1997

Poorly differentiated colonic adenocarcinoma, medullary type: clinical, phenotypic, and molecular characteristics.

Clinicopathological evidence has accumulated that colorectal adenocarcinoma with minimal or no glandular differentiation constitutes two entities with different prognosis. In a series of 20 predominantly nonglandular, poorly differentiated adenocarcinomas, histological features, DNA content, p53 protein expression, Ki-ras mutation, and microsatellite instability were analyzed and correlated to the biology of the tumors. In addition, the presence of Epstein-Barr virus (EBV) transcripts was tested by RNA in situ hybridization and EBV DNA was demonstrated by nested polymerase chain reaction. Histologically, 13 tumors showed small uniform cells and 7 tumors showed large pleomorphic cells. Tumors with uniform cells exhibited more commonly an expansive growth pattern (69.2% versus 0%; P < 0.025) and a dense peritumor lymphoid infiltrate (84.6% versus 14.3%; P < 0.01) resembling their gastric counterpart, solid or medullary carcinoma. These tumors showed less frequent lymph node as well as hematogeneous metastases than pleomorphic carcinomas. In addition, they were usually diploid (84.6% versus 28.6%; P < 0.05) and lacked stabilization of the p53 protein (0% versus 42.9%; P < 0.05). No significant difference between the medullary and the pleomorphic tumor type was found with respect to bcl2 expression and the occurrence of Ki-ras mutations at codon 12. In contrast, microsatellite instability was almost totally restricted to poorly differentiated adenocarcinomas of the medullary type (100% versus 14.3%; P < 0.001). Finally, polymerase chain reaction revealed EBV DNA in 5 tumor specimens, which was, however, restricted to the peritumor lymphoid infiltrate as shown by in situ hybridization. Correlation with the biology of the tumors revealed that only one patient with the uniform cell type died due to metastastic disease during the follow-up period (median, 31 months), which was the case in five of the seven patients with the pleomorphic-type carcinoma (P < 0.025). Our results clearly indicate that the poorly differentiated colonic carcinoma with minimal or no glandular structures constitute two different entities, a medullary and a pleomorphic variant, which markedly differ in their phenotype, genotype, and prognosis.

Adult↗
PubMed1997

[Acute hemolytic crisis as the initial manifestation of Wilson disease].

A 25-year-old woman who had delivered a normal child after a normal pregnancy four months ago, was suffering from a common cold. The latter was treated by tetracyclines. A few days later she developed an acute severe hemolysis. Moreover she had signs of hepatic failure which was characterized by a considerably reduced synthetic capacity of the liver but low serum aminotransferase levels and a proximal renal tubular disorder. With a negative Coombs test an autoimmune hemolytic anemia was unlikely. Therefore diagnostic procedures were directed at the cause of the liver injury. An increased urinary excretion of copper, strongly elevated levels of liver tissue copper and the detection of a Kayser-Fleischer ring by slit-lamp examination proved the diagnosis of Wilson's disease-presenting clinically only as severe hemolysis. Ceruloplasmin concentration in serum was in low normal range and not diagnostic.

Acute Disease↗
PubMed1997

Beneficial effect of ursodeoxycholic acid on mucosal damage in trinitrobenzene sulphonic acid-induced colitis.

BACKGROUND: Recently we observed that ursodeoxycholic acid (UDCA) ameliorates an experimental small intestinal inflammation induced by indomethacin in the rat. In this study, we have tested whether ursodeoxycholic acid also reduces mucosal damage in the bile-independent trinitrobenzene sulphonic acid (TNB) model of experimental colitis. METHODS: Intestinal inflammation (colitis) was induced in male Sprague-Dawley rats (250-300 g) by intracolonic administration of TNB (30 mg in 50% ethanol). Rats were treated with UDCA (10 mg/kg) either for 3 days starting with the administration of TNB for an acute inflammation (n = 11) or for 8 days starting one day after induction of colitis related to a more acute/chronic inflammation (n = 11). Rats were sacrificed at day 3 or day 9, respectively. Healing of induced colitis was assessed by macroscopic and blinded microscopic analysis as well as by measurement of bowel wet weight, daily body weight, and myeloperoxidase activity. All examinations were separately performed in three colon segments (S1 3-5 cm, S2 5.5-8 cm and S3 8.5-11 cm from anus). RESULTS: UDCA treatment significantly reduced macroscopically and microscopically detectable injury in acute inflammation in segments 1 and 2. The colitis-rats with acute/chronic inflammation had less marked mucosal damage. Nevertheless, UDCA treatment led to a significant decrease of visible injury parameters which was seen exclusively at the area of maximal ulceration (S2). Furthermore, a significant increase in body weight of UDCA-treated TNB rats compared to controls from day 5 on was found. CONCLUSION: Ursodeoxycholic acid attenuates the severity of acute inflammation and inhibits the development of acute/chronic inflammation predominantly around the area of maximal ulceration in TNB-induced colitis. In addition to our previous studies and results in indomethacin induced enteritis, these data may provide a rationale for studying how UDCA modulates functions of immune cells in the colonic mucosa.

Animals↗
PubMed1996

The helix-loop-helix transcription factor SEF-2 regulates the activity of a novel initiator element in the promoter of the human somatostatin receptor II gene.

The effects of somatostatin hormones are mediated by a family of five different seven-helix transmembrane spanning receptors (SSTR1-5). The expression of the five different SSTR subtypes displays a complex temporal- and tissue-specific pattern. To investigate the molecular mechanisms controlling the different expression patterns of the SSTRs, we cloned the 5'-flanking region of the human SSTR2 gene. Characterization of the SSTR2 promoter resulted in the identification of a novel initiator element (SSTR2inr). Transcriptional activity of the SSTR2inr is dependent on the presence of a binding site (E-box) for basic helix-loop-helix (bHLH) transcription factors. By screening a mouse brain cDNA expression library we isolated a cDNA coding for the bHLH transcription factor SEF-2. SEF-2 binds to the E-box present in the SSTR2inr, both in vitro and in vivo and activates transcription from the SSTR2inr. A single point mutation within the E-box eliminates binding of SEF-2 and results in a complete loss of transcriptional activity of the SSTR2inr. Furthermore, DNA binding studies demonstrate that the basal transcription factor TFIIB can be tethered to the SSTR2inr through physical interaction with SEF-2. In summary, the SSTR2inr represents a novel type of initiator element that confers gene expression in the absence of a TATA-box or binding sites for other known initiator factors, like YY-1 or USF.

Amino Acid Sequence↗
PubMed1996

Genomic instability in colorectal carcinomas: comparison of different evaluation methods and their biological significance.

In order to demonstrate the relationship between microsatellite instability and other types of genomic instability, a series of 56 sporadic colorectal carcinomas was investigated by flow cytometrical ploidy analysis, oligonucleotide fingerprinting, and microsatellite polymerase chain reaction (PCR). Stabilization of the p53 gene product was analysed by immunohistochemistry and proliferative activity was determined flow cytometrically and by silver staining of nucleolar organizer regions (AgNORs). Of the 56 carcinomas, 11 (19 per cent) exhibited microsatellite instability; 33 of the cases were aneuploid (59 per cent) and 29 (52 per cent) showed alterations of the oligonucleotide fingerprints. There was a significant correlation of microsatellite instability with localization of these tumours proximal to the splenic flexure, diploid DNA content, and less frequent p53 stabilization. A solid growth pattern, mucinous differentiation, and a Crohn's-like lymphoid infiltrate were also characteristic for those tumours. The results demonstrate for the first time a significantly lower proliferative activity in tumours with microsatellite instability. Data obtained from DNA flow cytometry or from oligonucleotide fingerprinting did not correlate with such tumour characteristics. It is proposed that the use of microsatellite PCR facilitates specifically the detection of a group of colorectal cancers which may differ in pathogenesis and perhaps prognosis.

Adult↗