PubMed Health⌕ Search

Biomedical subjects

Andreas Jung

Publications and source records attributed to Andreas Jung.

35 records · Page 2Linked to original sources
PubMed2004

Beta-catenin up-regulates the expression of the urokinase plasminogen activator in human colorectal tumors.

Expression of the urokinase plasminogen activator (uPA) increases during the progression of colorectal tumors from adenomas to carcinomas. The highest amounts of uPA are found at the invasion front of carcinomas, which also displays a strong expression of nuclear beta-catenin and is therefore a region expressing beta-catenin target genes at high levels. Here we show that beta-catenin contributes to the transactivation of uPA. Therefore, beta-catenin might have an impact on the capacity of colorectal tumors for invasion and metastasis, as well as dormancy, which are hallmarks of cancer.

Cell Line, Tumor↗
PubMed2004

Prognostic significance of microsatellite instability in curatively resected adenocarcinoma of the small intestine.

Adenocarcinoma of the small intestine (ACSI) is a rare condition with few studies addressing follow-up and prognosis. Tumors of 35 patients with curative resection of an ACSI were retrospectively analyzed by immunohistochemistry: p53, hMLH1, hMSH2 and hMSH6 and microsatellite instability (MSI): BAT-26, BAX, TGF-beta RII. With a median follow up of 6.1 years, the median cancer-specific survival (CSS) was 36.2 months. Patients who were highly instable (MSI-H) (n=10) had a CSS of 49.6 months in contrast to patients with stable tumors (23.2 months) (P=0.010). Additionally, a low tumor stage according to UICC and MSI-H were shown to be independent factors (P=0.005 and P<0.001) for an increased survival in multivariate analysis. Therefore, it is suggested that analysis of the MSI status might prove useful in discerning prognosis within cancers of the same stage.

Adenocarcinoma↗
PubMed2004

Beta-catenin activates a coordinated expression of the proinvasive factors laminin-5 gamma2 chain and MT1-MMP in colorectal carcinomas.

In colorectal carcinomas, loss-of-function mutations of the adenomatous polyposis coli (APC) tumor suppressor gene lead to a nuclear accumulation of the oncogenic transcriptional activator beta-catenin, predominantly at the invasive front within the tumor host interface. Various identified genes activated by beta-catenin are associated with tumor invasion. One prerequisite for malignant tumor invasion is the ability of tumor cells to migrate. We recently described the gamma2 chain of laminin as another beta-catenin target gene. Fragments of the laminin gamma2 chain, resulting from cleavage by the membrane type 1 matrix metalloproteinase (MT1-MMP), are strong inducers of epithelial cell migration. We here show a coordinated expression of nuclear beta-catenin, its target gene and MT1-MMP substrate laminin gamma2 chain, as well as MT1-MMP in tumor cells at invasive regions of colorectal carcinomas. We further demonstrate that MT1-MMP expression is regulated by beta-catenin/TCF through a TCF binding site in its promoter. These results suggest that nuclear beta-catenin activates the coordinated expression of the interacting proinvasive proteins laminin gamma2 chain and MT1-MMP, thereby leading to a promigratory activity at the invasive front of colorectal cancers. This further supports an important role of beta-catenin for invasion and metastasis of colorectal carcinomas.

Adenocarcinoma↗
PubMed2004

Evidence for acid-induced loss of Cdx2 expression in duodenal gastric metaplasia.

Gastric metaplasia in the duodenum (GMD) is characterized by transdifferentiation of intestinal epithelial cells into gastric foveolar cells within the duodenal mucosa. GMD is often associated with duodenal ulceration. Higher duodenal acidity due to increased gastric acid output into the duodenum has been implicated in the development of GMD. Intestinal development and homeostasis are controlled by the homeobox transcription factor Cdx2, which is considered to be the master regulator of intestinal differentiation. Using immunohistochemistry, the present study shows that GMD is associated with loss of expression of Cdx2 and its target gene product sucrase-isomaltase. Quantitative RT-PCR experiments using the intestinal cell line Caco2 revealed that Cdx2 and sucrase-isomaltase were down-regulated and gastric mucins MUC5AC and MUC6 were up-regulated under acidic culture conditions. Thus, it is suggested that increased acid exposure leads to GMD by impairing the transcription of Cdx2 and subsequently that of its intestine-specific target genes.

Adult↗
PubMed2003

The non-clonal and transitory nature of HIV in vivo.

From a posteriori analyses of genetic variation, recombination can only be identified when the parental genomes are distinct. For viruses like HIV-1, this requires the producer cell to be infected by more than one virus. Using fluorescence in situ hybridisation, the provirus copy numbers in splenocytes from two HIV-1 patients were determined. More than 75% of infected splenocytes harboured two or more proviruses, range 1-8, with a mean of approximately 3-4 per cell. Sequencing of amplified DNA from single laser micro-dissected cells showed an extraordinary degree of diversity while numerous recombinants were evident. Given the dynamics of HIV-1 turnover in vivo and a recombination rate of approximately 3 cross-overs per cycle, some genomes from a fifteen year old infection may have undergone as many cross-overs as bases in the genome. Thus, recombination profoundly influences HIV evolution and gives it a non-clonal and transitory nature in vivo.

HIV Infections↗
PubMed2003

Detection of Chlamydia pneumoniae but not of Helicobacter pylori in symptomatic atherosclerotic carotids associated with enhanced serum antibodies, inflammation and apoptosis rate.

BACKGROUND AND PURPOSE: Numerous seroepidemiological and pathological studies linked Chlamydia pneumoniae and Helicobacter pylori with atherosclerosis. However, analyses of these infectious agents in the pathogenesis of stroke are either lacking or contradictory. Therefore, we evaluated the detection rate of C. pneumoniae and H. pylori in normal carotids vs. atherosclerotic carotids and compared these findings with serology, plaque morphology, inflammatory cell infiltrates and apoptosis rate. METHODS: The study was performed on 40 morphological normal carotids from autopsy and 20 advanced atherosclerotic carotids from endarterectomy after stroke. Serum IgG antibody titre was measured by enzyme immunoassay (H. pylori) and microimmunofluorescence (MIF) technique (C. pneumoniae). Immunohistochemistry (IHC) and Western blotting were performed to identify C. pneumoniae, H. pylori, to characterize plaque morphology (macrophages and smooth muscle cells) and the inflammatory infiltrate (T- and B cells) and to detect apoptosis (TUNEL staining). RESULTS: C. pneumoniae was found significantly more frequently in atherosclerotic than in normal carotids (P=0.001), which correlated with elevated C. pneumoniae IgG-antibody titres (P=0.048). Although H. pylori was not detected in carotids, elevated H. pylori antibody titres were significantly associated with the degree of atherosclerosis (P=0.001). The C. pneumoniae infected carotids displayed a slightly enhanced infiltrate of T cells and apoptosis rate, but no morphological changes. CONCLUSION: C. pneumoniae but not H. pylori, was detected by IHC primarily in symptomatic carotids, without specific morphological differences. Correlation of C. pneumoniae in-situ-detection and IgG antibodies suggested a possible connection between respiratory-tract and endovascular infection. The C. pneumoniae associated T-lymphocytes and apoptosis rate indicate an immune-mediated inflammatory process, involving vascular walls.

Aged↗
PubMed2003

Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia.

We report here that individuals with Noonan syndrome and juvenile myelomonocytic leukemia (JMML) have germline mutations in PTPN11 and that somatic mutations in PTPN11 account for 34% of non-syndromic JMML. Furthermore, we found mutations in PTPN11 in a small percentage of individuals with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML). Functional analyses documented that the two most common mutations in PTPN11 associated with JMML caused a gain of function.

Animals↗
PubMed2003

Orbital rhabdomyosarcoma in Noonan syndrome.

The incidence of various benign and malignant tumors is increased in patients with Noonan syndrome compared with the general population. We present a 9-year-old boy with the typical features of Noonan syndrome and an acute nonaxial proptosis of the right eye. An ultrasound scan, a computed tomography scan, and magnetic resonance imaging raised suspicion of rhabdomyosarcoma. Biopsy confirmed the diagnosis. The tumor was consequently treated with combined chemotherapy and radiotherapy. Rhabdomyosarcoma is a rare but important differential diagnosis of tumor formation in children with Noonan syndrome and may arise in the orbit.

Brachytherapy↗
PubMed2003

Linear geometric ICA: fundamentals and algorithms.

Geometric algorithms for linear independent component analysis (ICA) have recently received some attention due to their pictorial description and their relative ease of implementation. The geometric approach to ICA was proposed first by Puntonet and Prieto (1995). We will reconsider geometric ICA in a theoretic framework showing that fixed points of geometric ICA fulfill a geometric convergence condition (GCC), which the mixed images of the unit vectors satisfy too. This leads to a conjecture claiming that in the nongaussian unimodal symmetric case, there is only one stable fixed point, implying the uniqueness of geometric ICA after convergence. Guided by the principles of ordinary geometric ICA, we then present a new approach to linear geometric ICA based on histograms observing a considerable improvement in separation quality of different distributions and a sizable reduction in computational cost, by a factor of 100, compared to the ordinary geometric approach. Furthermore, we explore the accuracy of the algorithm depending on the number of samples and the choice of the mixing matrix, and compare geometric algorithms with classical ICA algorithms, namely, Extended Infomax and FastICA. Finally, we discuss the problem of high-dimensional data sets within the realm of geometrical ICA algorithms.

Algorithms↗
PubMed2002

Recombination: Multiply infected spleen cells in HIV patients.

The genome of the human immunodeficiency virus is highly prone to recombination, although it is not obvious whether recombinants arise infrequently or whether they are constantly being spawned but escape identification because of the massive and rapid turnover of virus particles. Here we use fluorescence in situ hybridization to estimate the number of proviruses harboured by individual splenocytes from two HIV patients, and determine the extent of recombination by sequencing amplified DNA from these cells. We find an average of three or four proviruses per cell and evidence for huge numbers of recombinants and extensive genetic variation. Although this creates problems for phylogenetic analyses, which ignore recombination effects, the intracellular variation may help to broaden immune recognition.

Amino Acid Sequence↗
PubMed2002

T-cell factor-4 frameshift mutations occur frequently in human microsatellite instability-high colorectal carcinomas but do not contribute to carcinogenesis.

Colorectal carcinomas with microsatellite instability accumulate errors in short repetitive DNA repeats, especially mono and dinucleotide repeats. One such error-prone A(9) monorepeat is found in exon 17 of the TCF-4 gene. TCF-4 and beta-catenin form a transcription complex, which is important for both maintenance of normal epithelium and development of colorectal tumors. To elucidate the relevance of frameshift mutations in the TCF-4 in colorectal carcinogenesis, a variety of investigations in human tumors and cell lines was performed. It was found that mutations in the TCF-4 A(9) repeat do not contribute to tumorigenesis and seem to be passenger mutations.

Colorectal Neoplasms↗
PubMed2002

Beta-catenin and the morphogenesis of colorectal cancer.

Tumor growth and progression are morphogenetic processes that are characterized by ongoing changes in tumor structure and differentiation. These processes show similarities to morphogenesis in embryonic development, as supported by the fact that the main pathways regulating morphogenesis in early embryogenesis and organogenesis are directly or indirectly altered in most neoplasms. In colorectal adenocarcinomas, different morphogenetic areas can be clearly defined. The focus of this review is on combining morphology-based aspects and recent molecular and genetic data on the progression of colorectal carcinomas. The decisive genetic alteration in most colorectal cancers is the loss of function mutation in the adenomatous polyposis coli tumor suppressor gene, leading to an accumulation of the oncoprotein beta-catenin, the main effector of the embryonic Wnt/wingless pathway. The possibility is discussed that, on the basis of this genetic alteration, the tumor microenvironment is an additional driving force of tumor progression.

Colorectal Neoplasms↗
PubMed2002

Expression of the recombination-activating genes in extrafollicular lymphocytes but no apparent reinduction in germinal center reactions in human tonsils.

V(D)J recombination in lymphocytes is mediated by 2 recombination-activating genes, RAG1 and RAG2, which are expressed during lymphocyte development in bone marrow and thymus. Prompted by studies reporting re-expression of the RAGs in germinal center B cells, the expression of RAGs and terminal deoxynucleotidyl transferase (TdT) in human lymphoid tissues was examined using in situ hybridization and immunohistochemistry, respectively. Here it is shown that RAGs and TdT are not reinduced in germinal center reactions. However, RAG(+)/TdT(+) cells are frequently present in extrafollicular areas of tonsils mainly at the boundary between lymphoid tissue and fibrous scaffold. Phenotypic analyses suggest that these cells are B cells. Finally, it is shown that RAG(+)/TdT(+) cells are found more frequently in tonsils than in other peripheral lymphoid tissues. This may reflect an increased influx of RAG(+)/TdT(+) cells as a result of higher antigenic stimulation at this site. Alternatively, this observation may indicate that the tonsils are an additional site of lymphocyte ontogeny.

Adolescent↗
PubMed2002

Generation and characterization of human monoclonal scFv antibodies against Helicobacter pylori antigens.

Infection with Helicobacter pylori is chronic despite a vigorous cellular and humoral immune response and causes severe pathology in some patients. In this study, phage display was used as a new approach in order to investigate the role of the host's humoral immune response in the pathogenesis of H. pylori gastritis. Human monoclonal single-chain Fv (scFv) antibody fragments against H. pylori cell lysate and the H. pylori urease were isolated from an immune phage display library, constructed from peripheral blood lymphocytes of an H. pylori-infected patient. After affinity selection, 23% of the clones tested showed binding activity against a lysate of the H. pylori Sydney strain in enzyme-linked immunosorbent assay (ELISA) and 9% bound the H. pylori urease. Further characterization by PCR-fingerprint analysis and sequencing revealed that two closely related H. pylori binders and one antiurease scFv could be isolated. The selected scFvs were highly specific as analyzed by ELISA and immunoblots using various bacterial lysates and recombinant proteins. Analysis of the humoral immune response following H. pylori infection using human monoclonal antibodies might contribute to a better understanding of the pathogenesis of the disease. Moreover, using immune phage display libraries, it might be possible for relevant epitopes of H. pylori antigens to be determined, which might be of use for vaccine development.

Aged↗
PubMedDate not supplied

Relationship between sleeping posture and fluctuations in nocturnal scrotal temperature.

Elevated testicular temperatures are a potential risk factor for impaired spermatogenesis and reduced semen quality. The development of portable devices for the measurement of scrotal temperatures closely correlating with testicular temperature offered the opportunity to identify periods with high scrotal temperatures during daily life. Notably, sleeping periods covering approximately 1/3 of the day are associated with increased scrotal temperatures to around 36 degrees C. Combining infrared video taping with scrotal temperature profiling, our study clarified that sudden drops of scrotal temperature during sleep are the consequence of changes of posture. Nocturnal scrotal temperatures were significantly higher during sleeping on the side compared with periods lying on the back (+0.65 degrees C, right scrotum, P<0.001; +0.54 degrees C, left scrotum, P<0.001). Median values of nocturnal scrotal temperatures did not significantly differ between 11 volunteers with normozoospermia and 22 men with oligozoospermia. Furthermore, continued scrotal temperature profiling during the following day only showed significantly higher values among men with oligozoospermia than among volunteers for the left scrotal side (+0.70 degrees C, P<0.05), but not for the right scrotal side (+0.39 degrees C, P>0.05). This difference could not be attributed to higher scrotal temperature values during periods with physical inactivity (median in both groups above 36 degrees C) but the duration of physical inactivity in men with oligozoospermia was 50% longer than in volunteers. Thus, in the setting of the present study it was not possible to demonstrate a close correlation between scrotal temperature and semen quality.

Activity Cycles↗
PubMedDate not supplied

Seasonal changes of neutral alpha-glucosidase activity in human semen.

Although there are contradictory reports, the biochemical evaluation of the seminal activity of neutral alpha-glucosidase (NAG) has repeatedly been described as an important parameter to test epididymal patency and is recommended by the WHO. Because, for a number of diagnostic parameters, seasonal variations have been described even in the human, it was the aim of this study to investigate possible circannual changes of NAG. This is an important aspect of andrological diagnosis, as seasonal changes of specific diagnostic parameters might have an impact on the accuracy and predictive power of these parameters, which in turn might have an effect on the therapeutic concept for the patients. In a total of 473 patients, sperm concentration, volume of the ejaculate, total motility, progressive motility, pH value, number of peroxidase-positive cells, concentration of fructose, and NAG as functional markers of the seminal vesicles and the epididymis, respectively, were analyzed according to standard procedures. Seminal activity of NAG was significantly correlated with the sperm concentration (P < .0001), ejaculate volume (P < .0001), and the pH (P = .0025). Moreover, significant (P = .0008) seasonal changes in the activity of seminal NAG with the maximum in spring (76.87 mU/ejaculate) and the minimum in autumn (58.55 mU/ejaculate) were found. The incidence of low-ranged activity of the enzyme was 9.2% in spring, while it was 20.3% in autumn. Thus, our data clearly demonstrate circannual changes of the seminal activity of neutral alpha-glucosidase. This in turn has clinical impact as the predictive power of the test system changes throughout the year.

Adolescent↗