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Biomedical subjects

M Jung

Publications and source records attributed to M Jung.

At least 37 records · Page 2Linked to original sources
PubMed2003

Methylation status of p14ARF and p16INK4a as detected in pancreatic secretions.

The clinical management of pancreatic disease is often hampered by a lack of tissue diagnosis. Endoscopic pancreatography offers the opportunity to investigate exfoliated cells. However, the significance of mere cytological investigation is compromised by an insufficient sensitivity. The evaluation of the molecular background of carcinogenesis hopefully is capable of providing more sensitive diagnostic markers. The p16INK4a-/retinoblastoma tumour-suppressive pathway has been shown to be involved in the development of near to all pancreatic neoplasms. p14ARF is another tumour suppressor located in the immediate neighbourhood of p16INK4a. Promoter methylation has been demonstrated to be a major inactivating mechanism of both genes. We sought to further evaluate the role of the gene locus INK4a methylation status in the endoscopic differentiation of chronic inflammatory and neoplastic pancreatic disease. Pancreatic fluid specimens of 61 patients with either pancreatic carcinoma (PCA: 39), chronic pancreatitis (CP: 16) or a normal pancreatogram (NAD: 6) were retrieved. In order to detect methylation of either the p14ARF or the p16INK4a promoter a methylation-specific PCR protocol was applied. While 19 out of 39 patients with PCA showed p16 promoter methylation (49%), none of the 16 patients with CP revealed p16 promoter methylation. p14ARF methylation was found in a lower percentage of PCA specimens and in none of the samples of patients with CP. These results suggest a specific significance of INK4a for the development of malignant pancreatic disease. Our data further indicate a potential role for INK4a methylation as a diagnostic marker in the endoscopic differentiation of benign and malignant pancreatic disease.

Adenocarcinoma↗
PubMed2003

[Ceftriaxone versus Levofloxacin for antibiotic therapy in patients with acute cholangitis].

INTRODUCTION: For the therapy of acute cholangitis complete biliary drainage and antibiotic therapy is needed. The aim of the current study was to compare intravenous therapy of acute cholangitis with Ceftriaxone or Levofloxacin in a prospective and randomized fashion. METHODS: Patients with biliary obstruction and clinical signs of infection received in addition to 1.5 g Metronidazole either 500 mg Levofloxacin/die or 2 g Ceftriaxone/die. Early on during ERCP, bile was aspirated via the cannulation catheter and cultured for bacteria under aerobic and anaerobic conditions. Minimal inhibitory concentrations of the respective antibiotics were determinate for each isolate. The clinical course was followed for at least 6 days with clinical and laboratory data. RESULTS: 60 patients with clinical signs of acute cholangitis were randomised. In 40 patients (66 %) biliary colonization with bacteria could be identified. In all bacterial species Levofloxacin showed significantly lower rates of in-vitro resistance as compared to Ceftriaxone. However, the percentage of patients with a clinical cure or significant improvement was the same in the two groups. CONCLUSIONS: The clinical effect of Levofloxacin and Ceftriaxone in patients with acute cholangitis showed no significant differences. Because of improved in-vitro efficiency, a calculated therapy with Levofloxacin might be advantageous.

Acute Disease↗
PubMed2003

Standardized reprocessing of reusable colonoscopy biopsy forceps is effective: results of a German multicenter study.

BACKGROUND AND STUDY AIMS: National and international guidelines recommend that a standardized protocol consisting of cleaning, ultrasound cleaning, and sterilization should be used for the reprocessing of endoscopic accessories in order to reduce the risk of transmission of microorganisms. This German multicenter study investigated the efficacy of standardized reprocessing of reusable biopsy forceps used during colonoscopy. MATERIALS AND METHODS: Ten endoscopy centers (eight hospitals and two private practices) used 330 biopsy forceps during routine colonoscopy. The forceps were used once, five times, or 20 times for colonoscopy, based on a randomization plan. The reprocessing protocol consisted of manual cleaning with an enzymatic agent, ultrasound cleaning with an enzymatic agent (30 min, 40 degrees C, 47 Hz), neutralization, drying, and sterilization (5 min, 134 degrees C). Aldehydes were not used, and the protocol did not include a disinfection step. The biopsy forceps were sent to three microbiological institutes, based on a randomization plan, to have them tested for the presence of organisms, including identification of bacteria. RESULTS: A total of 318 of the 330 forceps were evaluable; 314 forceps (98.74 %) were sterile after use once, five times, or 20 times. Four forceps were contaminated with Staphylococcus epidermidis (n = 2), Bacillus licheniformis (n = 1) and Corynebacterium aquaticum (n = 2). All of 25 forceps were sterile after being used 20 times. CONCLUSION: Colonoscopy biopsy forceps can be reliably reprocessed following this standardized protocol, even without aldehydes.

Bacteria↗
PubMed2003

Value of chromoendoscopy and magnification endoscopy in the evaluation of duodenal abnormalities: a prospective, randomized comparison.

BACKGROUND AND STUDY AIMS: Endoscopic staining methods are increasingly being used to evaluate lesions in the esophagus and colon. The aim of this prospective study was to investigate chromoendoscopy and magnification endoscopy for the evaluation of mucosal lesions in the duodenum. PATIENTS AND METHODS: Consecutive patients were randomly assigned to undergo conventional endoscopy without staining (group A) or intravital staining of the duodenal mucosa with indigo carmine and evaluation with a conventional video endoscope (group B) or a magnification endoscope (group C). Visible lesions were characterized before and after staining, and biopsies were taken for histological assessment. RESULTS: A total of 118 patients was examined. Chromoendoscopy detected significantly more lesions in the duodenal bulb (98 vs. 28; P = 0.0042) in more patients (29 vs. 15; P = 0.0025) compared with conventional endoscopy (group A). After mucosal staining, there was no difference between video endoscopy and magnification endoscopy with regard to the number or extent of the lesions identified. Significantly more targeted biopsies were possible after intravital staining. The most commonly identified lesions on targeted biopsies included (staining/control groups): gastric metaplasia (14/3), hyperplastic Brunner's glands (6/3), inflammatory changes (7/6), villous atrophy (1/3), adenoma (1/0). CONCLUSIONS: Intravital staining of the duodenum with indigo carmine may be useful for detecting mucosal abnormalities, delineating their extent, and allowing targeted biopsies. Magnification endoscopy, when used in addition to chromoendoscopy, does not appear to further increase the diagnostic yield for detecting duodenal abnormalities.

Adolescent↗
PubMed2002

[Adenomas of Vater's ampulla and of the duodenum. Presentation of diagnosis and therapy by endoscopic interventional and surgical methods].

BACKGROUND: Adenoma of the ampulla of Vater and the duodenum are rare tumors. The leading symptoms are unspecific; sometimes they are due to the disturbances of the passage or erosion of the tumor. Early and correct diagnosis and the appropriate therapy are of decisive importance because these tumors are precancerous. PATIENTS AND METHODS: We report the cases of seven patients with periampullary adenoma of the duodenum, in one case with incorporation of the the distal bile duct. The diagnostic steps and the surgical treatment are reported and discussed. In achieving a definitive diagnosis, endoscopic retrograde cholangiopancreatography is of paramount importance. Three patients subsequently underwent partial pancreatoduodenectomy (Whipple's procedure); in three patients transduodenal local tumor excision was performed. Postoperative course was without complications in each case and no operative mortality occurred. One patient was treated by argon-coagulation. RESULTS: The histopathological examination showed a tubular villous adenoma in six cases and in one case a villous adenoma (ranging from low to high grade dysplasia). Because there is evidence of an adenoma-carcinoma-sequence, radical surgical treatment is recommended, even in adenoma with low grade dysplasia, in spite of the absence of malignancy.

Adenoma↗
PubMed2002

[Reprocessing of flexible endoscopes and endoscopic accessories - an international comparison of guidelines].

Endoscopic examinations and procedures are essential for diagnosis and treatment of gastrointestinal diseases. As a result of poor reprocessing practice microorganisms can be transmitted via endoscope. The majority of infection transmissions is due to insufficient performance of cleaning and disinfection disregarding guidelines of societies of gastrointestinal endoscopy. A review of the literature and a comparison of European and American guidelines for reprocessing flexible endoscopes are given. Differences in the classification of endoscopic devices, on the possibility of prion transmission, recommendations on staff training and protection, quality assurance of reprocessing and evidence-based graduation of guidelines are stressed and discussed. With respect to the procedure of endoscope reprocessing, differences concerning the cleaning solution to choose, necessity of thoroughly manual cleaning and brushing of the accessible endoscope channels (even in the case of subsequent automatic reprocessing endoscopes in washers-disinfectors), disinfection solution, microbiological quality of water for final rinsing and rationale for alcohol flush of endoscope channels for better drying are mentioned. The need for experimental investigations of the cleaning and disinfection process is stressed. In contrast to recent guidelines of European and American societies of gastrointestinal endoscopy, the now updated recommendations of the Robert Koch-Institute for reprocessing flexible endoscopes and endoscopic accessories are evidence-based and graduated.

Cross Infection↗
PubMed2001

The genome of the natural genetic engineer Agrobacterium tumefaciens C58.

The 5.67-megabase genome of the plant pathogen Agrobacterium tumefaciens C58 consists of a circular chromosome, a linear chromosome, and two plasmids. Extensive orthology and nucleotide colinearity between the genomes of A. tumefaciens and the plant symbiont Sinorhizobium meliloti suggest a recent evolutionary divergence. Their similarities include metabolic, transport, and regulatory systems that promote survival in the highly competitive rhizosphere; differences are apparent in their genome structure and virulence gene complement. Availability of the A. tumefaciens sequence will facilitate investigations into the molecular basis of pathogenesis and the evolutionary divergence of pathogenic and symbiotic lifestyles.

Agrobacterium tumefaciens↗
PubMed2001

CoMFA of artemisinin derivatives: effect of location and size of lattice.

A CoMFA study of artemisinin derivatives with changes of the location and the number of lattice points was performed. The location of probe atoms in a large lattice has practically no effect on the cross-validated r(2) value (r(2)(cv)). The selection of only 18 probe atoms around the peroxide bond, considering the action mechanism of artemisinin, provided a less time-demanding and more reliable CoMFA model, which forecasts better than the large lattice model despite the lower r(2)(cv) value. Only 1 A displacement of the small lattice caused a reduction of cross-validated r(2) value of more than 50%, which indicates the lattice location played an important role in this small lattice model.

Antimalarials↗
PubMed2001

Ionizing radiation-induced apoptosis in ataxia-telangiectasia fibroblasts. Roles of caspase-9 and cellular inhibitor of apoptosis protein-1.

Ionizing radiation (IR) has been shown to induce apoptosis to a greater extent in a fibroblast cell line AT5BIVA derived from an individual with ataxia-telangiectasia (AT) than in control fibroblasts. However, the signaling pathway that underlies IR-induced apoptosis in AT cells has remained unknown. The mechanism of apoptosis in response to gamma-irradiation has now been examined in three AT fibroblast lines (AT3BIVA, AT4BIVA, and AT5BIVA) derived from different individuals with AT. The apoptotic indexes of these cell lines at 72 h after irradiation were 12, 31, and 35%, respectively, compared with a value of 2.3% for control fibroblasts. Immunoblot analysis and fluorometric assays revealed that the extents of IR-induced activation of caspase-3 and caspase-9 were markedly greater in AT4BIVA and AT5BIVA cells than in AT3BIVA and control cells. Furthermore, the basal abundance of the apoptotic inhibitor, a cellular inhibitor of apoptosis proteins (c-IAP-1), was markedly reduced in AT4BIVA and AT5BIVA cells compared with that in AT3BIVA and control cells. The overexpression of either caspase-9 mutant forms or recombinant c-IAP-1 in AT5BIVA cells inhibited the IR-induced activation of caspases-3 and 9 and reduced the apoptotic index of the irradiated cells. These results indicate that the extent of IR-induced apoptosis in different AT cell lines is inversely related to the abundance of c-IAP-1 and directly related to the extent of activation of caspases-3 and 9.

Amino Acid Substitution↗
PubMed2001

Role of ATM in oxidative stress-mediated c-Jun phosphorylation in response to ionizing radiation and CdCl2.

Ionizing radiation-induced phosphorylation of the transcription factor c-Jun is impaired in cells derived from individuals with ataxia telangiectasia (AT), in which the ATM gene is mutated. We demonstrate here that ATM modulates c-Jun phosphorylation following exposure to ionizing radiation as well as treatment with CdCl(2), a potent pro-oxidant. Exposure of AT and control fibroblasts to CdCl(2) induced a biphasic increase in c-Jun phosphorylation on serine residues 63 and 73, with the extent of the second phase being markedly greater in AT cells than in control cells. Heme oxygenase-1, a marker of oxidative stress, was also significantly induced in AT fibroblasts. Expression of recombinant ATM in AT fibroblasts, however, reduced the extent of the effects of CdCl(2) on both c-Jun phosphorylation and heme oxygenase-1 induction. Our data suggest that ATM contributes to oxidative stress-mediated signaling that leads to c-Jun phosphorylation by acting as a sensor of ionizing radiation-induced oxidative stress and by modulating intracellular redox homeostasis.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2001

Improvement and validation of the fluorescence-based histone deacetylase assay using an internal standard.

The determination of the activity of histone deacetylase (HDAC) and the potency of its inhibitors has become an important goal in medicinal chemistry. This is due both to the involvement of HDAC in gene regulation and the ability of its inhibitors to modulate transcription and induce differentiation and/or apoptosis in cancer cells. We have previously reported the development of a non-isotopic assay for HDAC using a fluorescent derivative of epsilon-acetyl lysine. It can replace existing methods that rely on radioactively labeled histones or oligopeptides as substrates. Here we report validation and improvement of the procedure using an internal standard for the quantitation of the fluorescent substrate by HPLC.

Animals↗
PubMed2001

BDNF increases the number of axotomized rat retinal ganglion cells expressing GAP-43, L1, and TAG-1 mRNA--a supportive role for nitric oxide?

The death of neurons and the limited ability to activate growth-associated genes prevent the restoration of lesioned fiber tracts in the adult mammalian CNS. Here, we characterized the effects of the survival-promoting neurotrophin brain-derived neurotrophic factor (BDNF) on mRNA expression of GAP-43, L1, TAG-1, and SC-1 in axotomized and regenerating rat retinal ganglion cells (RGCs). BDNF led to de novo upregulation of TAG-1 mRNA in axotomized RGCs and to a threefold increase in the number of GAP-43 and L1 mRNA-expressing RGCs. SC-1 expression remained unchanged. However, BDNF did not improve long-distance axon regeneration into a peripheral nerve graft. Surprisingly, potentiating BDNF-mediated neuroprotection by simultaneous administration of a spin trap or a NOS inhibitor counteracted the BDNF-induced growth-associated gene expression. This led us to hypothesize that the BDNF effects on GAP-43, L1, and TAG-1 mRNA expression are mediated by a NO-dependent mechanism. In summary, our data support the idea that survival and axon regeneration of lesioned CNS neurons can be regulated independently.

Animals↗
PubMed2001

A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer.

Cisplatin-based chemotherapy improves survival in appropriately selected patients with stage IV non-small cell lung cancer (NSCLC). However, cisplatin-based regimens have well-known dose-related toxicities, particularly renal insufficiency and neurotoxicity. On the basis of prior preclinical and phase I studies, we initiated a phase II study of SPI-77 (STEALTH) Liposomal Cisplatin) in patients with stage IIIB and IV NSCLC who failed previous treatment with platinum. Disease in all subjects had progressed during therapy, failed to respond, or progressed within 3 months after discontinuing the platinum-based chemotherapy. Between January and June 1999, 13 patients were enrolled at our institution. Patient characteristics included: seven women, six men; median age, 61 years; median Karnofsky performance status, 80%; median number of prior chemotherapy regimens, two (range, 1-3). All patients had adequate hepatic and renal function. SPI-77 was administered at a dose of 260 mg/m(2) IV every 3 weeks. A median of two cycles (range 1-6) were given; the total number of cycles was 35. Among the 12 patients evaluable for response, two had (17%) stable disease and ten (83%) had progressive disease. The median survival was 24.3 weeks, and the median follow-up was 43.9 weeks. Toxicity could be evaluated in all subjects. Moderate anemia (46% of cycles, or=grade 3) with minimal granulocytopenia and thrombocytopenia (26% of cycles grade 1; 0% of cycles, >or=grade 2) were the most notable manifestations of myelosuppression. Grade 3 nonhematological toxicities included dyspnea (8%), fatigue (8%), and pain (8%). There were no grade 4 toxicities. These data suggest that this liposomal cisplatin formulation does not have appreciable activity in this population of patients with NSCLC who had received prior platinum-based chemotherapy. The lack of encouraging results from SPI-77 use in other phase I and II studies resulted in early closure of this trial by the manufacturer.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Epigenetic targeting in the mouse zygote marks DNA for later methylation: a mechanism for maternal effects in development.

The transgenic sequences in the mouse line TKZ751 are demethylated on a DBA/2 inbred strain background but become highly methylated at postimplantation stages in offspring of a cross with a BALB/c female. In the reciprocal cross the transgene remains demethylated suggesting that imprinted BALB/c methylation modifiers or egg cytoplasmic factors are responsible for this striking maternal effect on de novo methylation. Reciprocal pronuclear transplantation experiments were carried out to distinguish between these mechanisms. The results indicate that a maternally-derived oocyte cytoplasmic factor from BALB/c marks the TKZ751 sequences at fertilization; this mark and postzygotic BALB/c modifiers are both required for de novo methylation of the target sequences at postimplantation stages. Using genetic linkage analyses we mapped the maternal effect to a locus on chromosome 17. Moreover, seven postzygotic modifier loci were identified that increase the postimplantation level of methylation. Analysis of interactions between the maternal and the postzygotic loci shows that both are needed for de novo methylation in the offspring. The combined experiments thus reveal a novel epigenetic marking process at fertilization which targets DNA for later methylation in the foetus. The most significant consequence is that the genotype of the mother can influence the epigenotype of the offspring by this marking process. A number of parental and imprinting effects may be explained by this epigenetic marking.

Alleles↗