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Biomedical subjects

A Jung

Publications and source records attributed to A Jung.

At least 19 recordsLinked to original sources
PubMed1999

beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer.

Most colorectal cancers have loss of function mutations in the adenomatosis polyposis coli (APC) tumor suppressor gene. This leads to accumulation of beta-catenin, which together with the DNA binding protein TCF-4 functions as a transcriptional activator. Recently defined target genes are c-myc and cyclin D1, linking the APC gene defect to the capacity for autonomous proliferation of colon tumors. Here we report the identification of the matrix metalloproteinase MMP-7 as another target gene of beta-catenin/TCF-4. MMP-7 is overexpressed in 80% of human colorectal cancers and known to be an important factor for early tumor growth, with a potential function also for later progression steps, like invasion and metastasis. Our results explain the high percentage of MMP-7 overexpression in colon tumors. Moreover they indicate that defects in the APC tumor suppressor gene may also have an influence on later steps of colon tumor progression.

Biomarkers, Tumor↗
PubMed1999

Negative regulation of CD4 expression in T cells by the transcriptional repressor ZEB.

ZEB, an E-box binding transcriptional repressor, is an important regulator of T cell and muscle development. Targeted disruption of ZEB in mice resulted in a strong reduction of thymocytes and the few T cells that reached the mature stage were predominantly CD4(+). CD4 expression during the various stages of T cell differentiation is controlled at the transcriptional level by a complex array of regulatory elements in the CD4 gene locus, consisting of at least three enhancers, one promoter and one silencer. Here we present evidence that CD4 gene expression is negatively regulated by ZEB. We show that ZEB binds to the 5'E-box in the CD4-3 element of the proximal CD4 enhancer in competition with the transcriptional activators E12 and HEB, thereby reducing CD4 expression on CD4 single-positive but not CD4/CD8 double-positive T cells. The conversion of the CD4 proximal enhancer into a potential silencer element by the transcriptional repressor ZEB offers an additional concept of CD4 gene regulation in T cells.

Animals↗
PubMed1998

Potentiation of D2-dopamine receptor-mediated suppression of zif 268 by non-competitive NMDA receptor antagonists in reserpinized rats.

Striatopallidal output neurons, which coexpress D2-dopamine receptors and NMDA receptors, are logically a potential site of interaction between corticostriatal glutamatergic input and dopaminergic systems. Recent hypotheses about the etiology of schizophrenia have implicated both excitatory amino acid and dopamine systems. The present study was designed to examine, in vivo, the interaction between D2-dopamine receptors and NMDA receptors in the regulation of the expression of the early immediate genes (IEGs), zif 268 and jun B, in striatopallidal neurons. We tested whether coadministration of NMDA antagonists interacted with the actions of the D2 agonist, quinpirole, on IEG expression following dopamine depletion with reserpine. When rats were pretreated with the non-competitive NMDA receptor antagonists, MK 801 (1 mg/kg) or PCP (20 mg/kg), together with quinpirole, the quinpirole reversal of reserpine induction of zif 268 mRNA was potentiated in all regions examined. MK 801 alone had no significant effect on reserpine induction of zif 268 mRNA. Pretreatment with the competitive NMDA receptor antagonist, CPP (5 mg/kg), did not significantly alter the dose response of zif 268 mRNA expression to quinpirole in any region. There was no significant effect of MK 801 on jun B mRNA expression, either on the response to quinpirole or when administered alone with reserpine. Our findings provide evidence of an interaction between the NMDA receptor channel system and the D2-dopamine system on a molecular level in striatopallidal neurons carrying output from the basal ganglia.

Animals↗
PubMed1998

[Arthritis as first symptom of leukemia in children].

Three children out of 30 (10%) referred for juvenile chronic arthritis had leukaemia. The patients had complained of intermittent musculoskeletal pain and painful joint swelling for three weeks, nine months and eighteen months prior to admission. On admission two of the patients had active arthritis with soft tissue swelling in one and three joints respectively. The third patient had only arthralgias and no joint swelling. All patients had slight anaemia, normal to slightly reduced thrombocyte count, slight neutropenia and absence of blasts in the peripheral blood. The correct diagnosis was made by bone marrow aspiration. Two children had acute lymphoblastic leukaemia and the third acute myeloblastic leukaemia. Leukaemia thus remains an important differential diagnosis in children presenting with musculoskeletal pain and/or arthritis.

Arthritis, Juvenile↗
PubMed1998

Predictive value of nuclear beta-catenin expression for the occurrence of distant metastases in rectal cancer.

PURPOSE: Adenomatous polyposis coli protein, glycogen synthetase kinase-3-beta, T cell transcription factor/lymphoid enhancer-binding factor, and beta-catenin modulate cell differentiation and proliferation via the expression of effector genes. It has recently been postulated that beta-catenin is a potent oncogene of sporadic colorectal carcinogenesis and a prognostic tumor marker. Our aim was to investigate whether the nuclear overexpression of beta-catenin, possibly caused by mutations in exon 3 of beta-catenin (CTNNB1), is correlated with distant metastatic spread or disease-free survival in rectal carcinoma. METHODS: Immunohistochemical analysis was performed with an anti-beta-catenin-monoclonal antibody on paraffin sections of two groups of patients (n = 2 x 77) with rectal carcinoma curatively treated by surgery alone. The patients selected were all free of local disease, to exclude surgical influence. Patient groups were matched for age, gender, International Union Against Cancer stage, and year of operation (1982 to 1991) and differed only in subsequent metachronous distant metastatic spread. Follow-up was prospective (median, 9.6 years). Three staining patterns were defined: membranous (normal), diffuse cytoplasmic (pathologic), and intense nuclear staining (pathologic). When intense nuclear staining was defined, the specimen was microdissected. Then, DNA was isolated, polymerase chain reaction-amplified, and sequenced to detect mutations in exon 3. RESULTS: Nuclear overexpression of beta-catenin correlated neither with distant metastatic spread (chi-squared, 0.37; P = 0.79) nor with disease-free survival (log-rank with trend, P = 0.62). No mutations were found in the area of the serine/threonine-kinase glycogen synthetase kinase-3-beta-phosphorylation site in exon 3 (CTNNB1) of beta-catenin. CONCLUSION: Although beta-catenin seems to play an important role in early colorectal carcinogenesis, its value as a prognostic marker is questionable. It must be assumed that metastatic ability is determined by other factors than the disturbance of the beta-catenin T cell transcription factor/lymphoid enhancer-binding factor cascade and that other mechanisms might cause the observed nuclear translocation of beta-catenin.

Adenocarcinoma↗
PubMed1998

Apoptosis in chronic gastritis and its correlation with antigastric autoantibodies.

In the course of time, chronic gastritis may result in gastric atrophy, as in type A gastritis, where autoimmune reactions against parietal cells result in a loss of corpus glands. Two antigastric autoantibodies have been detected in Helicobacter pylori gastritis and are described as anti-luminal and anti-canalicular autoantibodies. The aim of this study was to determine whether increased apoptosis may be responsible for the loss of gastric epithelium and whether this apoptosis is correlated with antigastric autoimmunity. Gastric biopsies from normal mucosa and Helicobacter pylori gastritis were analysed for the presence of apoptosis using the TUNEL method. Helicobacter pylori gastritis was divided into cases (1) without autoantibodies, (2) with anti-luminal, and (3) with anti-canalicular autoantibodies. Apoptotic cells of the foveolar and of the glandular epithelium in the antrum and corpus were counted. The number of apoptotic cells in the gastric mucosa was significantly increased in all cases of gastritis. The highest number of apoptotic cells was observed in the gastric glands of the corpus mucosa in Helicobacter pylori gastritis with anti-canalicular autoantibodies. Apoptosis contributes to the development of gastric atrophy and there are various types of Helicobacter pylori gastritis. The positive correlation between apoptotic cell loss in the glandular zone of the corpus mucosa and the presence of anti-canalicular autoantibodies indicates a possible link between anti-gastric autoimmunity and atrophy in this type of Helicobacter pylori gastritis--similar to that in classic type A gastritis.

Adult↗
PubMed1998

Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front.

Sixty to eighty percent of all colorectal cancers are characterized by mutations in the APC tumor suppressor gene. Recently, it was shown that these mutations lead to a nuclear overexpression of beta-Catenin by disruption of the wingless/WNT signal pathway. Since nuclear beta-Catenin functions as a transcriptional activator of hitherto unknown tumor genes, this form of beta-Catenin is now considered a major oncoprotein in colorectal cancer. Using immunohistochemistry, we investigated the distribution of overexpressed beta-Catenin within individual colorectal carcinomas. In the majority of the tumors, we found no homogeneous staining, but a strong nuclear expression of beta-Catenin predominantly localized at the invasion front with strongest nuclear staining of isolated, scattered tumor cells. In contrast, cells in the tumor center often showed no nuclear staining, but retained a membranous expression of beta-Catenin, comparable to normal colon epithelium. It is, therefore, likely that in addition to the overexpression of beta-Catenin caused by defects in the APC locus, regulatory events in the tumor itself lead to a different distribution of this oncoprotein. Possibly, surrounding tissue at the invasion front can give signals to the tumor cells, leading to a nuclear translocation of beta-Catenin, where it may play a direct role in tumor invasion processes.

Cell Nucleus↗
PubMed1998

[Resection and replacement of the cervical esophagus and hypopharynx--an interdisciplinary responsibility for visceral, micro- and ENT surgeons].

From 1984 to 1996, 136 carcinomas of the esophagus and 8 of the hypopharynx were resected using 3 different procedures (94 transmediastinal, 36 transthoracic, 14 cervicoabdominal). The hospital mortality rate for cervicoabdominal resection (0%) is unequivocally lower than that of the transmediastinal (17.1%) or transthoracic (14.3%) methods. The 5-year survival rates are not significantly different (24%, 22%, 17%).

Adult↗
PubMed1997

An electrophysiological analysis of altered cognitive functions in Huntington disease.

BACKGROUND: Neuropsychological deficits are a main feature of Huntington disease (HD) with previous data suggesting involvement of memory functions and visual processing. OBJECTIVE: To increase the knowledge about cognitive malfunction in HD in the domains of visual processing and memory by the use of modern electrophysiological techniques (event-related potentials [ERPs]). DESIGN: A case-control design was used. Three ERP paradigms were used; a parallel visual search paradigm allowed for the simultaneous processing of a multi-element visual array in search of a target stimulus, while a serial search paradigm with varied numbers of distractor items necessitated a serial one by one scanning of the arrays. The third experiment was a word-recognition memory task. SETTING: The measurements were obtained in a neurophysiological laboratory of a university hospital. PATIENTS AND CONTROLS: Nine patients with HD and 9 control subjects matched for age, sex, and education were studied. MAIN OUTCOME MEASURES: Components of averaged ERPs were quantified by latency and amplitude measures and subjected to statistical analysis. Behavioral measures (search time, hit rate, and recognition accuracy) were assessed as well. RESULTS: The early visual components showed a significant latency shift (delay of about 50 milliseconds) in HD. In the search paradigms the P3 components differentiating target and standard stimuli were virtually absent in HD as was the ERP effect indexing word recognition. This was accompanied by a marked delay in search times and lower hit rates in the search tasks and a grossly reduced recognition accuracy in the memory task. CONCLUSIONS: The results suggest marked impairments of patients with HD in early visual sensory processing (early components). Deficits in visual search might be attributed to an impairment to deploy attentional resources across the visual field and/or an inability to control eye movements. The ERPs in the memory task differed grossly from similar data obtained by others in patients with Alzheimer disease, suggesting a different neural basis for the amnesia in HD.

Adult↗
PubMed1997

The incidence of port-site metastases might be reduced.

BACKGROUND: Laparoscopic resection for cancer is controversial and port-site metastases are not infrequent. The mechanisms of occurrence of port-site metastases remain unclear. Animal experiments have suggested a role for carbon dioxide (CO2), but port-site metastases also occur after thoracoscopy, where no CO2 is used. The aim of this study was to define the role of CO2 in the seeding of tumor cells in the human patient. METHODS: CO2, instruments, trocars, suction device, and peritoneal washing were examined during 12 staging laparoscopies for pancreatic cancer. The presence, viability, and biological significance of cells were investigated using conventional cytology, polymerase chain reaction (PCR), and restriction fragment length polymorphisms (RFLPs) to detect the presence of a mutant k-ras gene as a genetic marker of cancer cells. RESULTS: Cytology exam of peritoneal washing, instruments, the suction device, and trocars revealed many cells. Tumor cells were detected in 6/12 peritoneal, in 4/12 trocars and 4/11 instruments washings, but not in 12 CO2 samples. The DNA content of CO2 was very low-as assessed by PCR. Mutant DNA was detected by RFLP in four out of 12 aerosols. Six aerosols did not contain any DNA. Two aerosols were borderline. CONCLUSIONS: During staging laparoscopy for pancreatic cancer in humans, CO2 contains only very low levels of free-floating tumor cells, even in the presence of massive peritoneal contamination. These results suggest that the incidence of port-site metastases might be reduced if mechanical contamination of the port sites with instruments or with the specimen can be avoided.

Adenocarcinoma↗
PubMed1997

[Regional cooperation in molecular biology topics].

Research on rare events, such as the occurrence of port-site metastases, can be speeded up by pooling patients from different hospitals. Multidisciplinary approaches, involving surgeons, pathologists and molecular biologists, allow more detailed experimental results to be obtained. Research costs are kept low by using existing infrastructures over a short period of time.

Cost-Benefit Analysis↗
PubMed1996

Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11.

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.

Chromosome Mapping↗
PubMed1996

Ageing and sperm function.

To evaluate the fertilizing capacity of spermatozoa from elderly men, ejaculates from 29 older fathers (mean age 50.3 years) were compared with those from 35 younger fathers (mean age 32.2 years). In addition to conventional semen parameters, sperm functions were studied that have been reported to be positively correlated with the fertilization rate: progressive motility, acrosin activity, inducible acrosome reaction, and chromosome condensation. Sperm concentration and follicle stimulating hormone concentration differed significantly in both groups. With regard to sperm functions there were no differences between older men and younger men, except for decreased sperm motility in the older group which, however, reached nearly normal values according to World Health Organization criteria. Decreased fertility of older couples is obviously more dependent on the age of the female partner. The significance of genetic risks remains to be clarified, especially when methods of assisted reproduction are applied.

Acrosin↗
PubMed1996

Adjunctive controlled topical application of tetracycline HCl in the treatment of localized persistent or recurrent periodontitis. Effects on clinical parameters and elastase-alpha1-proteinase inhibitor in gingival crevicular fluid.

35 patients receiving regular supportive periodontal therapy (SPT) and showing signs of localized persistent or recurrent periodontitis were enrolled in the study. Within 1 week after SPT, each patient had a tetracycline HCl loaded ethylene vinyl acetate co-polymer fiber placed into the periodontal pocket of 1 randomly selected tooth with persistent or recurrent periodontitis (test); the fiber was removed after 9.5+/-2.0 days. A non-adjacent tooth with persistent or recurrent periodontitis in a separate quadrant, which received no further treatment, served as a control. A total of 28 patients completed the 6-month study. Compared to control teeth, in test teeth at 6 months significantly (p<0.01) lower scores were found for gingival index, pocket probing depths, and PMN elastase-alpha1-proteinase inhibitor concentrations in gingival crevicular fluid. With the exception of plaque index scores, test teeth demonstrated significant reductions from baseline to 6 months in all parameters (p<0.05). Conversely, all parameter measurements in control teeth, except bleeding on probing, showed no significant difference between baseline and 6-month values. The results suggest that the use of controlled topical application of tetracycline HCl may improve periodontal health and reduce the risk of disease progression in localized persistent or recurrent periodontitis. Moreover, the effects of this application appear to be sustained for at least 6 months.

Administration, Topical↗
PubMed1996

[Use of thermographic methods for estimation of skin prick test results. II. Evaluation of skin prick test results with histamine solutions of different concentration using liquid crystal mixtures].

The aim of the study was to evaluate the usefulness of liquid crystal thermography in interpretation of skin prick tests with selected allergens and different solutions of histamine. The study group consisted of 35 young adults with indications for skin prick tests, and in whom skin tests with different solutions of histamine were also carried out (10 mg of histamine per 1 ml diluted to a concentration of 1:1, 1:10, 1:100). The skin reaction was assessed visually after 15 minutes, measuring flare and wheal diameter and utilizing the liquid crystal thermographic method--assessing the diameter of each colour green, blue, violet. For statistical purposes the area was also calculated. A correlation of each area was performed with the wheal and flare diameter. The area of the skin reaction was largest for both methods using the undiluted solution of histamine, the smallest using the 1:100 dilution. The liquid crystal thermographic method showed larger areas of skin lesions than those using only the visual method by analyzing the size of the wheal and flare. Due to this fact skin tests should be carried out at lest 9 cm apart from each other. The largest correlation was found between diameter of the flare and area of blue colour of the liquid crystal thermographic method (registering the temperature of 34.3 degrees C-36.3 degrees C). Using the thermographic method a joint temperature analysis of the wheal and flare lesions are performed. The results of this study correspond with the earlier, preliminary studies showing the usefulness of the liquid crystal thermographic method in assessing skin reactions to different allergens and histamine solutions.

Adolescent↗