Biomedical subjects

A Jung

Publications and source records attributed to A Jung.

At least 37 records · Page 2Linked to original sources

PubMed2002

Fundic gland polyps (Elster's cysts) of the gastric mucosa. A marker for colorectal epithelial neoplasia?

The results of several retrospective studies allow us to conclude that the detection of fundic gland polyps (Elster's cysts) is associated with an increased incidence of colorectal tumors. In this survey, we present the results of a prospective study investigating such a possible relationship. A total of 144 patients were investigated, of whom 80 had fundic gland polyps of the gastric corpus mucosa. Sixty-four of these patients underwent a colonoscopy, whereas the other 64 patients belonged to a sex- and age-matched control group with no fundic gland polyps. In the group with known fundic gland polyps, colorectal neoplasias were found in 29 (45.3%) patients. Eight of these patients had (12.5%) adenocarcinomas, 3 (4.7%) had high-grade intraepithelial neoplasia, and 18 (28.1%) had tubular adenomas. In one patient, a synchronous carcinoma of the rectum and the colon was detected. In comparison, 6 patients of the control group (9.3%) developed tubular adenomas and 9 (14.1%) had hyperplastic polyps of the colonic and rectal mucosa. Our results suggest that it is necessary to conduct a careful diagnostic work-up of the colon in patients with gastric fundic gland polyps.

Biomarkers, Tumor↗

PubMed2002

7-Deaza-2'-deoxyguanosine allows PCR and sequencing reactions from CpG islands.

CpG islands are GC rich sequences that are found in the promoters of many genes in higher eukaryotes. They contain a high frequency of CG dinucleotides, which are substrates for DNA methylases. Methylation leads to transcriptional silencing of promoters. Owing to their high GC content CpG islands exhibit strong base-base interactions, which lead to superstructures and consequently to regions with higher melting temperatures. Therefore, Taq polymerases (especially sequenases) fall off their templates, causing premature termination of the polymerase chain reaction (PCR) or sequencing reactions. The results from such reactions are thus insufficient for further analysis. Therefore, we have evaluated the use of 7-deaza-2'-deoxyguanosine for PCR amplification of the human p16(INK4A) promoter and sequencing of HUMARA exon 1 PCR products. Our results show that the addition of 7-deaza-2'-deoxyguanosine significantly improves results, particularly when small amounts of poor quality DNA are available as starting material.

Base Sequence↗

PubMed2002

Sequential genotyping of Pseudomonas aeruginosa from upper and lower airways of cystic fibrosis patients.

A controversy exists concerning the adequate specimen to characterise colonisation of cystic fibrosis (CF) airways by Pseudomonas aeruginosa. Oropharyngeal, sputum and bronchoalveolar lavage samples were evaluated from 38 stable CF patients for the detection of P. aeruginosa, genetically different isolates within the same host and longitudinal variations in the genotype during repeated examinations. Bacterial isolates were typed by pulsed-field gel electrophoresis of deoxyribonucleic acid macrorestriction fragments. Sensitivity, negative and positive predictive values and specificity to detect P. aeruginosa were 35.7, 73.5, 83.3 and 96.2% for oropharyngeal cultures in nonexpectorating patients and 91.7, 94.1, 100 and 100% for sputum cultures from expectorating patients, respectively. Genotypes of Pseudomonas isolates recovered from oropharyngeal swabs and sputum differed to the strains recovered by bronchoscopy in 55% and 40%, respectively. In 62% longitudinal variations in the genotype occurred. One-half of these alterations were detectable by bronchoscopy only. In conclusion, sputum samples were of equal value as specimens from bronchoalveolar lavage to detect Pseudomonas aeruginosa colonisation. Cultures from the oropharynx are not suitable for characterising bacterial conditions in the cystic fibrosis lung. Different genotypes within the same host and longitudinal genetic alterations are common and may be detectable in the bronchoalveolar lavage fluid exclusively.

Adolescent↗

PubMed2001

Expression of the invasion factor laminin gamma2 in colorectal carcinomas is regulated by beta-catenin.

The migration-inducing gamma2 chain of laminin-5, one of the best known invasion markers, is strongly overexpressed in disseminating and infiltrating tumor cells at the invasive front of colorectal carcinomas. The same tumor cells show nuclear accumulation of the oncoprotein beta-catenin, which together with T-cell factor-DNA-binding proteins, functions as transcriptional activator of genes involved in tumor progression. Here we show that beta-catenin activates the human laminin-5 gamma2 gene through two T-cell factor-binding elements in a synergistic manner together with hepatocyte growth factor and conclude that laminin-5 gamma2 is another important target gene of nuclear beta-catenin during tumor progression.

Adenocarcinoma↗

PubMed2001

Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment.

Invasion and dissemination of well-differentiated carcinomas are often associated with loss of epithelial differentiation and gain of mesenchyme-like capabilities of the tumor cells at the invasive front. However, when comparing central areas of primary colorectal carcinomas and corresponding metastases, we again found the same differentiated epithelial growth patterns. These characteristic phenotypic changes were associated with distinct expression patterns of beta-catenin, the main oncogenic protein in colorectal carcinomas, and E-cadherin. Nuclear beta-catenin was found in dedifferentiated mesenchyme-like tumor cells at the invasive front, but strikingly, as in central areas of the primary tumors, was localized to the membrane and cytoplasm in polarized epithelial tumor cells in the metastases. This expression pattern was accompanied by changes in E-cadherin expression and proliferative activity. On the basis of these data, we postulate that an important driving force for progression of well-differentiated colorectal carcinomas is the specific environment, initiating two transient phenotypic transition processes by modulating intracellular beta-catenin distribution in tumor cells.

Base Sequence↗

PubMed2001

Disassembly of microtubules and inhibition of neurite outgrowth, neuroblastoma cell proliferation, and MAP kinase tyrosine dephosphorylation by dibenzyl trisulphide.

Dibenzyl trisulphide (DTS), a main lipophilic compound in Petiveria alliacea L. (Phytolaccaceae), was identified as one of the active immunomodulatory compounds in extracts of the plant. To learn more about its biological activities and molecular mechanisms, we conducted one-dimensional NMR interaction studies with bovine serum albumin (BSA) and tested DTS and related compounds in two well-established neuronal cell-and-tissue culture systems. We found that DTS preferentially binds to an aromatic region of BSA which is rich in tyrosyl residues. In SH-SY5Y neuroblastoma cells, DTS attenuates the dephosphorylation of tyrosyl residues of MAP kinase (erk1/erk2). In the same neuroblastoma cell line and in Wistar 38 human lung fibroblasts, DTS causes a reversible disassembly of microtubules, but it did not affect actin dynamics. Probably due to the disruption of the microtubule dynamics, DTS also inhibits neuroblastoma cell proliferation and neurite outgrowth from spinal cord explants. Related dibenzyl compounds with none, one, or two sulphur atoms were found to be significantly less effective. These data confirmed that the natural compound DTS has a diverse spectrum of biological properties, including cytostatic and neurotoxic actions in addition to immunomodulatory activities.

Animals↗

PubMed2001

Expression of the recombination activating genes (RAG1 and RAG2) is not detectable in Epstein-Barr virus-associated human lymphomas.

The expression of the recombination activating genes (RAG1 and RAG2) is largely restricted to immature lymphoid cells. Previous studies have suggested that Epstein-Barr virus (EBV) infection may lead to a re-induction of RAG expression in mature B lymphocytes. To assess the significance of this mechanism for the pathogenesis of malignant lymphomas, we have examined the expression of RAG genes in 11 cases of EBV-associated endemic Burkitt's lymphoma (BL), 25 cases of Hodgkin's disease (HD, 17 EBV(+), 8 EBV(-)) and 10 cases of follicular non-Hodgkin's lymphoma (NHL). Using in situ hybridization, expression of the RAGs was detected in cortical thymocytes in normal thymus and in the tumor cells of 2 of 3 lymphoblastic NHL. By contrast, there was no detectable RAG expression in the BL, HD and follicular NHL cases. Our results indicate that re-induction of RAG expression does not occur in human lymphomas in vivo. Thus, it is unlikely to play a role in the development of translocations involving immunoglobulin gene loci which are characteristically found in BL and follicular NHL. Moreover, our study shows that in situ hybridization is a suitable method for the analysis of RAG expression in human tissue sections.

Burkitt Lymphoma↗

PubMed2001

[Infantile botulism caused by honey].

We report a case of a 5-week-old infant admitted with respiratory arrest. He had been fed with honey for two weeks. Infant botulism was suspected and confirmed by the finding of Clostridium botulinum toxin in the serum and faeces, and in the honey. The infant needed 7.5 months of ventilatory support.

Botulinum Toxins↗

PubMed2001

[Fever as etiology of temporary infertility in the man].

BACKGROUND AND OBJECTIVE: Fever of > or = 39 degrees C for > or = 3 days can lead to severely impaired semen quality and even azoospermia. Among spermatogenic cells, pachytene spermatocytes and spermatids are particularly sensitive to temperature. Because of the nature of a spermatogenic cycle, impairment of semen quality becomes obvious after a latent period of several weeks. The changes are usually reversible within a few months. Therefore, a careful history with regard to fever episodes during preceding 3 months is mandatory for interpretation of semen analysis. PATIENTS/METHODS: Five patients are reported who desired a child and had experienced high fever of > or = 39 degrees C for > or = 3 days. The results of semen analyses are presented in relation to fever episodes. RESULTS: Sperm concentration declined to 0.4-7% and fast progressive motility to 0-23% 3-6 weeks after the fever episodes and returned to base line levels within 4-6 months. In patients without semen analysis before the fever episode, semen quality remarkably improved thereafter. CONCLUSIONS: Investigating patients for a history of fever during the 3 months preceding fertility work-up avoids unreasonable treatment recommendations based on transient impairment of semen quality.

Fever↗

PubMed2001

Covalent strategy for immobilization of DNA-microspots suitable for microarrays with label-free and time-resolved optical detection of hybridization.

Sequence-specific detection and quantification of nucleic acids are central steps in many molecular biology procedures which have also been transferred to chip-based procedures. Hybridization-based assays can be used to quantify and discriminate between DNA target sequences down to the level of single base mismatches. Arrays of DNA probes immobilized on a support enable simultaneous testing of multiple sequences of a single sample. DNA arrays can be produced either by in-situ synthesis of oligonucleotides or by immobilization of pre-assembled DNA probes. Covalent and directed immobilization improves the reproducibility and stability of DNA arrays. This is especially interesting with repeated use of transducers or chips. Procedures are described for effective covalent immobilization of pre-assembled amino-linked oligonucleotides, by use of ink-jet techniques, on a modified and heated glass surface, with addressable surface areas ranging from 0.01 mm2 to a few mm2. Almost immediate evaporation of the spotted droplets on the heated surfaces leads to very high surface hybridization capacities. The surfaces are suitable for use with a label-free detection method - reflectometric interference spectroscopy (RIfS). It is shown that hybridization capacity and non-specific interaction at these DNA-surfaces can be characterized by use of RIfS. With a consumption of less than 80 ng mm(-2) oligonucleotide and a specific hybridization capacity of more than 300 fmol mm(-2), the activated aminodextran procedure was usually suitable for setting up a DNA array with label-free detection. Non-specific interactions with random oligomers or protein (ovalbumin) were low. Up to 150 repeated regenerations (stripping) of the surfaces by acid treatment and denaturing agents, and 50 days of storage, have been possible without significant loss of hybridization capacity.

DNA Probes↗

PubMed2001

Metaplasia, intraepithelial neoplasia and early cancer of the stomach are related to dedifferentiated epithelial cells defined by cytokeratin-7 expression in gastritis.

Cancer presumably arises from stem cells, preserved in an undifferentiated status since fetal development, or from a dedifferentiation of mature cells that return into a fetal phenotype with the potential for proliferation and renewal. Dedifferentiation in this context could represent a transient phase, passed through by cells, before they switch to redifferentiation, metaplasia or neoplasia. Cytokeratin-7 (CK7) is present in fetal, largely absent in normal adult, and transiently neoexpressed in metaplastic and neoplastic epithelial cells of the stomach according to previous observations. CK7 neoexpression in the stomach could, hence, define a fetal-like, dedifferentiated, cellular phenotype during the development of metaplasia and neoplasia. To test this hypothesis, we investigated CK7 expressions in fetal stomachs, non-neoplastic control stomachs, and neoplastic stomachs exhibiting metaplasia, intraepithelial neoplasia, and early cancer. Proliferation and beta-catenin expression of CK7-positive cells were also evaluated. The chronology of CK7 expression was studied during the experimental gastritis-cancer sequence in Mongolian gerbils. Our results show that metaplastic and neoplastic changes in the gastritis-cancer sequence are related to dedifferentiated epithelial cells which are defined by CK7 expression and can phenotypically be linked to fetal cells at the start of gastric pit development. The dedifferentiated cells exhibit a low proliferation and beta-catenin accumulation, similar to stem cells. Thus, the "stem cell" and "dedifferentiation" hypotheses for cancer origin could complement one another, and dedifferentiation-redifferentiation processes might be decisive for carcinogenesis in the stomach.

Adenocarcinoma↗

PubMed2001

Efficacy of surgical measures in preventing port-site recurrences in a porcine model.

BACKGROUND: Port-site recurrences are serious complications of laparoscopy performed for cancer. Incidences reported in the literature vary between 0% and 21%, suggesting an influence of the surgeon. METHODS: The aim of this experimental, prospective, randomized, single-blind study was to investigate the influence that the quality surgery has on the incidence of port-site recurrences. After a 12-mmHg carbon dioxide (CO2) pneumoperitoneum was created, 10(7) human HeLa cell were injected into the peritoneal cavity of 18 pigs, creating a xenogeneic tumor. Laparoscopic sigmoid resections then were performed using four trocars and a transanal double-stapling technique. The following protective measures were applied in nine animals: trocar fixation, prevention of gas leaks, rinsing of instruments with povidone-iodine, minilaparotomy protection, rinsing of trocars before removal, peritoneal closure, and rinsing of all wounds with povidoneiodine. Surgeons and type of procedures were randomized. After 4 weeks, the animals were killed and all portsites excised. Blinded immunohistologic analysis with antihuman pancytokeratin antibody was performed. RESULTS: Tumor recurrence was present in 23 of 36 port sites (63.8%) in the control group, but only in 5 of 36 port sites (13.8%) in the group that received protective measures (p = 0.002; Fisher's exact test). No peritoneal carcinosis nor anastomotic recurrences were observed. CONCLUSION: These results strongly suggest that the quality of surgical technique has an influence on the incidence of port-site recurrences. From now on, we propose to use these protective measures routinely in cancer laparoscopy.

Animals↗

PubMed2001

The invasion front of human colorectal adenocarcinomas shows co-localization of nuclear beta-catenin, cyclin D1, and p16INK4A and is a region of low proliferation.

At the invasion front of well-differentiated colorectal adenocarcinomas, the oncogene beta-catenin is found in the nuclear compartment of tumor cells. Under these conditions, beta-catenin can function as a transcription factor and thus activate target genes. One of these target genes, cyclin D1, is known to induce proliferation. However, invasion front of well-differentiated colorectal adenocarcinomas are known to be zones of low proliferation and express the cell cycle inhibitor p16INK4A. Therefore, we investigated the expression profiles of nuclear beta-catenin, cyclin D1, p16INK4A, and the Ki-67 antigen, a marker for proliferation, in serial sections of well-differentiated colorectal adenocarcinomas. Invasion fronts with nuclear beta-catenin were compared with areas from central parts of the tumors without nuclear beta-catenin, for the expression of cyclin D1, p16INK4A, and Ki-67. It was observed that expression of nuclear beta-catenin, cyclin D1, and p16INK4A at the invasion front are significantly correlated. Such areas exhibit low Ki-67 expression indicating a low rate of proliferation. Thus, in colorectal carcinogenesis the function of beta-catenin and its target gene cyclin D1 does not appear to be the induction of tumor cell proliferation. In particular, the function of cyclin D1 should be reconsidered in view of these observations.

Adenocarcinoma↗

PubMed2001

Cardiogenic embolism as the main cause of ischemic stroke in a city hospital: an interdisciplinary study.

BACKGROUND: It is essential to understand the pathogenesis of ischemic stroke to ensure rational acute therapy and secondary prevention. We wanted to know the distribution of pathogenesis in patients of a city hospital and the differences in risk factors, neurologic deficits, disability, and delay in clinical admittance. PATIENTS AND METHODS: During a period of one year, 222 patients (mean age 76.6 years; 59% women) with complete acute ischemic stroke were admitted and underwent complete clinical and diagnostic procedures: CCT/MRI; Doppler- and color-coded duplex and transcranial sonography; echocardiography; use of the NINCDS stroke scale and the Oxford disability scale; study of risk factors, and exploration of delay in admittance. RESULTS: The following percentages of etiologies were evident: 31% cardiogenic embolism (60% with atrial fibrillation), 13% microangiopathy, 9% macroangiopathy, 11% cerebellar or brain stem infarction, 18% more than one cause and 18% no cause found. The patients with cardiogenic embolism showed significantly the highest scores on the stroke scale and the disability scale and had the shortest delay in admittance (57% were admitted within 3 hours). CONCLUSIONS: In a city hospital, cardiogenic embolism is the main cause of ischemic stroke. These patients suffer significantly the most severe neurologic deficits, dependence, and requirement of daily nursing care. These patients have the shortest delay in clinical admittance and the best chance of benefitting from acute therapy and early secondary prevention.

Aged↗

PubMed2001

Fatal atypical T-cell proliferation associated with Epstein-Barr virus infection.

We report the case of a young Caucasian man who presented with polyneuropathy and severe, ultimately fatal, congestive heart failure in the context of a chronic active Epstein-Barr virus (EBV) infection. Post-mortem examination revealed both monoclonal and polyclonal proliferation of EBV-positive atypical T lymphocytes within different organs. Predominant infiltration of the nervous system and heart with extensive myocardial scarring accounted for the clinical symptoms. The remarkable features of this case are (i) the occurrence in a Caucasian patient, (ii) the absence of detectable immunodeficiency, and (iii) the myocardial destruction by EBV-infected monoclonal T cells.

Adult↗

PubMed2001

Frequency and spectrum of Malassezia yeasts in the area of the prepuce and glans penis.

OBJECTIVE: To investigate the frequency and spectrum of lipophilic Malassezia yeasts within the area of the glans penis and preputial space in healthy men, most of whom were uncircumcised. SUBJECTS AND METHODS: As the glans penis and the prepuce are abundant in sebaceous glands, 130 clinically healthy men were examined for the presence of Malassezia spp. Two impression preparations each were made on modified Dixon (mDixon) and Leeming-Notman agar. The media were used with no added cycloheximide to allow the identification of the full spectrum of Candida yeasts. After 10 days of incubation at 32 degrees C Malassezia and Candida yeasts were differentiated by micromorphological and biochemical criteria. RESULTS: Malassezia spp. were found as part of the microflora of the glans penis in 49% of the men. The two media yielded comparable results for isolation frequency and spectrum: On mDixon agar, 47.6% of the isolates were identified as M. sympodialis, 42.8% as M. globosa, 4.8% as M. pachydermatis and 2.4% as M. furfur. Candida spp. (especially C. albicans) were found in 20.8%. There were no significant differences in the distribution of different Malassezia spp with age. CONCLUSIONS: Malassezia yeasts may belong to the resident microflora of the male genital region, which is supported by the finding that free sebaceous glands ('Tyson's glands') normally occur at this site. They may also be involved in pathological processes of the glans penis, e.g. balanitis, seborrheic eczema or psoriasis.

Adolescent↗

PubMed2001

Tip60 is a cell-type-specific transcriptional regulator.

Tip60 was originally identified as cellular HIV-Tat interacting protein and has been shown to augment Tat-dependent transcription. It has also been shown to interact with various cellular transcription factors and to belong to the nuclear histone acetyltransferase (HAT) family. To further elucidate the function of Tip60 and its HAT domain in transcription regulation, we compared Tip60 activity in HeLa and Jurkat T lymphoma cells. Here we show that Tip60 augments the HIV-1 Tat activity at the HIV-LTR promoter in HeLa but inhibits it in Jurkat cells. Moreover, we isolated two new variants of the Tip60 protein (Tip60Delta1, Tip60Delta2) from Jurkat cells. The Tip60Delta2 variant lacks the entire HAT domain but modulates HIV-1 Tat activity like full-length Tip60. In addition, Tip60 and the transcriptional repressor ZEB (zinc finger E box binding protein) interact specifically in the yeast two-hybrid system and additively inhibit the CD4 enhancer/promoter activity in Jurkat cells. Thus, Tip60 may function as corepressor of the ZEB protein. In summary, these data show that Tip60 functions as a cell-type-specific transcriptional regulator and that the HAT domain is not required for either transcriptional activation or inhibition. This indicates that Tip60 may function by recruiting additional cell-type-specific cofactors.

Acetyltransferases↗

PubMed2001

ANT1, an aromatic and neutral amino acid transporter in Arabidopsis.

A new amino acid transporter was identified from the Arabidopsis expressed sequence tag cDNAs by expressing the cDNA in a yeast amino acid transport mutant. Transport analysis of the expressed protein in yeast showed that it transports aromatic and neutral amino acids, as well as arginine. This transporter (ANT1, aromatic and neutral transporter) also transports indole-3-acetic acid and 2,4-dichlorophenoxyacetic acid. The cDNA is 1.6 kb in length with an open reading frame that codes for a protein with 432 amino acids and a calculated molecular mass of 50 kD. Hydropathy analysis showed ANT1 is an integral membrane protein with 11 putative membrane-spanning domains. Southern analysis and a BLAST search of the Arabidopsis genome database suggests that ANT1 is part of a small gene family containing at least five members. Phylogenetic comparisons with other known amino acid transporters in plants suggests that ANT1 represents a new class of amino acid transporter. RNA gel-blot analysis showed that this transporter is expressed in all organs with highest abundance in flowers and cauline leaves.

Amino Acid Transport Systems, Neutral↗