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Biomedical subjects

M Rotter

Publications and source records attributed to M Rotter.

At least 37 records · Page 2Linked to original sources

Molecular characterization of a novel mammalian DnaJ-like Sec63p homolog.

We identified a human cDNA sequence encoding a polypeptide of 760 amino acids that shares 53% homology and 25.6% identity with the yeast DnaJ-like endoplasmic reticulum (ER) translocon component Sec63p. Three epitope-specific antisera revealed a protein of an apparent molecular mass of 83 kDa, both in human cell extracts and in dog pancreatic microsomes. Biochemical analyses show that it is an integral membrane protein of the rough ER, which has the DnaJ domain located in the ER lumen. The novel Sec63 protein could thus represent a key component of the mammalian ER protein translocation machinery.

Amino Acid Sequence↗

Type-1 plasminogen activator inhibitor in human renal cell carcinoma.

In experimental models, plasminogen activator-mediated degradation of the extracellular matrix is inhibited by type-1 plasminogen activator inhibitor (PAI-1). PAI-1 has also been shown to protect tumour stromal tissue from autoproteolytic activities and may thus substantially promote tumour growth and metastasis formation. Human renal cell carcinoma (RCC) cells express significant amounts of plasminogen activator activity. In the present study, the expression of its specific inhibitor PAI-1 has been investigated in 32 cases of RCC and compared with adjacent non-tumour renal tissues. RCC tissue exhibited higher levels of PAI-1, determined at both the antigen and the mRNA level by ELISA and Northern blot analysis respectively. Immunohistochemical analysis showed that PAI-1 antigen was primarily confined to tumour cells and vascular endothelium, a distribution similar to that previously reported for plasminogen activator activity in RCC. The close co-localization with endogenous plasminogen activator activity may be important in the regulation of RCC-associated proteolysis. The increased expression of PAI-1 and its predominant localization within the tumour may help to conserve tumour tissue integrity and may thus promote RCC progression and metastasis formation.

Blotting, Northern↗

European multicentre evaluation of a commercial system for identification of methicillin-resistant Staphylococcus aureus.

A commercial system for the rapid detection of methicillin-resistant Staphylococcus aureus, the BBL Crystal MRSA test (C-MRSA ID; Becton Dickinson, USA), was evaluated prospectively and compared with a polymerase chain reaction test for the presence of the mecA gene. Ten European centres tested a total of 676 isolates of Staphylococcus aureus from blood cultures. The system correctly identified 661 (97.8%) isolates within 4 h. All but three mecA gene-negative isolates (99.4% specificity) yielded a negative C-MRSA ID reaction, and 158 of 170 mecA gene-positive isolates were accurately detected (92.9% sensitivity). After repeated testing of discrepant results, sensitivity and specificity increased to 99% and 100%, respectively.

Bacteriological Techniques↗

[Procedures for hand hygiene in German-speaking countries].

According to the field of application, strategies for the prevention of the transfer of microbial skin flora from the hands must consider the various categories of flora: transient, resident or stemming from infected lesions on the hands (infection flora). Depending on the species and virulence of the microorganism and of the susceptibility of the infection target, transient flora may or may not be of pathogenic importance. In contrast, resident skin flora is usually regarded as pathogenic only under certain circumstances such as in surgery, especially with transplantation of foreign bodies and in highly susceptible hosts. Microorganisms stemming from infected lesions are of proven pathogenicity. In the non-surgical field, only the transient and infection flora from the hands play a role. Such lesions are an absolute contraindication for patient-care, preparation of pharmaceuticals or foodstuff. In some procedures, the transmission of transient flora can be prevented by use of the non-touch technique ("instruments instead of fingers") or by the intelligent use of protective gloves. Hands already contaminated may be rendered safe by procedures for the elimination of transients such as handwashing, hygienic handwash and hygienic hand rub (in the order of increasing efficacy). Among all useable chemicals, ethanol, isopropanol and n-propanol (in the order of increasing efficacy) are the strongest and fastest agents. Furthermore, the duration of treatment (between 30 and 60 s) significantly influences the achievable reduction of microbial release. According to the new European standards (CEN) for testing chemical disinfectants and antiseptics, products for hygienic handwash must be significantly more efficacious than unmedicated soap, on artificially contaminated hands. In contrast, products for the hygienic hand rub must not be significantly less efficacious than a reference disinfection including isopropanol 60% vol rubbed onto the hands of the same volunteers during 1 min. By this, the average reduction of microbial release amounts to 4.2 to 4.4 lg, in our hands. The effectiveness of procedures for the hygienic handwash is usually significantly lower than that of alcoholic rubs. Therefore, in hospitals, they can be used only in certain indications such as patient care in reverse isolation, preparation of pharmaceuticals or foodstuff. In the surgical field, where not only transient but also resident flora is a cause of post-operative infection, the microbial release from the hands of the surgical team into the surgical wound must be prevented by using surgical gloves. Because of frequent glove lesions, a surgical hand disinfection is usually performed before donning gloves to keep a possible inoculumn as small as possible. Also in this field of application, alcoholic rubs proved to be significantly more effective than washing hands with antiseptic detergents. There exists a strong positive correlation of the reduction of microbial release and the duration of hand treatment, between 1 and 5 min. The European test standards (CEN) require products for surgical hand disinfection to be at least as efficacious as a reference disinfection of clean hands, which are constantly rubbed and kept wet with n-propanol 60% vol during 3 min. By this, the achievable average reduction of the microbial release ranges between 2.0 and 2.4 lg. In contrast, antiseptic washing procedures with preparations containing povidone-iodine, chlorhexidine gluconate or triclosan reduce the bacterial release within 2-5 min only by 0.5 to 1.2 lg. Some of them exert a bacteriostatic sustaining effect which is not found with alcoholic preparations. This, however, is not necessary with the latter as the initial bacterial reduction is that strong that restitution of the skin flora takes > 3 hours. Alcoholic preparations are at least as tolerable for the skin as antiseptic detergents, if not better, if they contain suitable emollients. Because dilution renders alcohols i

Colony Count, Microbial↗

Lateral ventricular enlargement in schizotypal personality disorder.

Although an increase in the ratio of ventricular space to brain (ventricle-brain ratio), VBR) on computed tomography (CT) has been among the most robust findings in chronic schizophrenia, VBR has not been investigated in a large, well-characterized clinical population of patients with schizotypal personality disorder (SPD), a clinical entity with a phenomenologic, gentle biological, and treatment response relationship to chronic schizophrenia. Accordingly, CT scans were obtained in 36 male SPD patients, 23 males with other personality disorders, 133 male schizophrenic patients, and 42 male normal volunteers. The mean body of the lateral VBR was significantly greater in the SPD patients than in the patients with other personality disorders. The VBR of the SPD patients did not differ significantly from either that of the normal volunteers or the schizophrenic patients but was intermediate between the two groups. There were no correlations with either psychotic-like or deficit-related symptoms of SPD in either the SPD or total personality disorder cohorts. SPD patients, like schizophrenic patients, may have increased VBRs compared wit patients with other personality disorders; their VBRs fall between the means of schizophrenic patients and normal control subjects.

Adult↗

Activity of NK 611, a new epipodophyllotoxin derivative, against colony forming units from freshly explanted human tumours in vitro.

NK 611 is a new semisynthetic analogue of etoposide, which presumably also acts through inhibition of topoisomerase II, and has been found to be more potent against several cancer cell lines in vitro than etoposide. The objectives of our study were to determine the activity of NK 611 against freshly explanted clonogenic cells from human tumours and compare this agent with etoposide and other clinically useful agents. After exposure for 1 h in 45 evaluable tumour specimens, NK 611 showed clear concentration-dependent antitumour activity. At 51 microM, 49% of specimens were markedly inhibited. Using a long-term (21-28 day) exposure at 6.8 microM, 58% of 50 evaluable specimens were profoundly inhibited. At equimolar concentrations, NK 611 was as active as etoposide. Across all tumour types studied, NK 611 was as active as vinblastine, bleomycin, doxorubicin, 5-fluorouracil, mitomycin-C and cisplatin. Our results showed cross resistance to etoposide in the majority of specimens. Activity of NK 611 was greater with long-term exposure than with short-term exposure indicating schedule dependency. We conclude that NK 611 has a wide spectrum of in vitro antitumour activity. Since preliminary clinical information suggests that this drug is well tolerated at high doses, further development of this agent in Phase II trials with multiple dosing schedules is warranted.

Antineoplastic Agents↗

Modulation of urokinase and urokinase receptor gene expression in human renal cell carcinoma.

In vivo and in vitro experimental models have suggested a major role for the urokinase-type plasminogen activator (uPA) in tumor cell invasion and metastasis. The uPA proteolytic activity of tumor cells has been shown to be largely determined by the extent of the expression and saturation of the uPA receptor. We have analyzed the expression and cellular localization of both uPA and uPA receptor at the protein and mRNA levels in 33 paired samples of renal cell carcinoma (RCC) and non-tumorous kidney tissue. In comparison with adjacent normal non-tumorous kidney tissues RCC tumor cells modestly overexpressed uPA-receptor mRNA and showed significantly decreased uPA mRNA expression. However, the immunoreactive uPA content of tumor cells was comparable to that of the surrounding normal non-tumorous kidney tissue. Assuming constancy of the uPA-receptor affinity for uPA this indicates that a proportion of the RCC-associated uPA may be derived from an exogenous source and subsequently concentrated at the tumor cell surface via uPA receptor expression. The modest increase in uPA receptor expression may lead to a normalization of uPA antigen content in RCC; however, it is not sufficient to substantially increase tumor tissue-uPA content over the level of normal non-tumorous kidney tissue.

Blotting, Northern↗

Microsatellite instability in adenocarcinomas of the upper gastrointestinal tract. Relation to clinicopathological data and family history.

We analyzed 66 adenocarcinomas arising in the upper gastrointestinal tract for microsatellite instability at eight microsatellite loci to investigate the role of these genetic alterations in the etiology of these tumors. We identified alterations in at least one locus in 11/46 adenocarcinomas of the stomach, in 2/15 adenocarcinomas arising in Barrett's esophagus, and in 1/5 adenocarcinomas of the duodenum and jejunum. Microsatellite instability in gastric tumors was found in 5/22 of intestinal, 1/3 of mixed, and 5/21 of diffuse type tumors. No relationship to the tumor stage (TNM), age, and survival time of the patients was observed. One patient had two synchronous gastric tumors both exhibiting microsatellite instability at multiple loci. His family history revealed four individuals in the maternal line afflicted with gastric carcinoma in three generations. Our data show that microsatellite instability is a genetic event in 11 to 24% of tumors of the upper gastrointestinal tract. The observation of microsatellite instability and a familial clustering of gastric tumors may suggest a genetic predisposition for a subset of gastric tumors, which may be identified by microsatellite analysis.

Adenocarcinoma↗

Expression of M-cadherin protein in myogenic cells during prenatal mouse development and differentiation of embryonic stem cells in culture.

Molecules regulating morphogenesis by cell-cell interactions are the cadherins, a class of calcium-dependent adhesion molecules. One of its members, M-cadherin, has been isolated from a myoblast cell line (Donalies et al. [1991] Proc. Natl. Acad. Sci. U.S.A. 88:8024-8028). In mouse development, expression of M-cadherin mRNA first appears at day 8.5 of gestation (E8.5) in somites and has been postulated to be down-regulated in developing muscle masses (Moore and Walsh [1993] Development 117:1409-1420). Affinity-purified polyclonal M-cadherin antibodies, detecting a protein of approximately 120 kDa, were used to study the cell expression pattern of M-cadherin protein. It was first visualized in somites at E10 1/3 and could be confined to desmin positive, myotomal cells. At all subsequent prenatal stages, M-cadherin was only found in myogenic cells of somitic origin. The detection of the protein at E10 1/3 suggests a translational delay of M-cadherin mRNA of 1 to 2 days (E8.5 vs. E10 1/3). This was further supported by the finding that during differentiation of ES cell line BLC6 into skeletal muscle cells in culture, expression of M-cadherin mRNA can be detected 2 days prior to M-cadherin protein. During prenatal development, the pattern of M-cadherin expression changes: In E10 1/3 embryos and also in myotomal cells of later stages, M-cadherin is evenly distributed on the cell surface. In developing muscle masses (tested at E16 to E18), however, M-cadherin protein becomes clustered most likely at sites of cell-cell contact as indicated by double-labelling experiments: M-cadherin-staining is the positive image of laminin negative areas excluding the presence of a basal lamina at M-cadherin positive sites. Furthermore, M-cadherin is coexpressed with the neuronal cell adhesion molecule N-CAM which has been shown to mediate cell-cell contact in myogenic cells. In summary, our results are in line with the idea that M-cadherin might play a central role in myogenic morphogenesis.

Amino Acid Sequence↗

[Resistance spectrum of staphylococci at the Vienna general hospital (July to December 1991)].

This study describes the antibiotic resistance of 1961 staphylococcal strains that were isolated at the University Hospital of Vienna from July to December 1991. Staphylococcus aureus (SA) represented 43.2%; coagulase-negative (CNS) staphylococci 56.8%, three quarters of which were Staphylococcus epidermidis. Excepting netilmicin, the proportion of resistant strains to all antibiotics was higher with CNS than SA. Methicillin resistance (M(r)) was found in 11.8% of SA and 30.3% of CNS. Borderline oxacillin resistance (BOR) was noted in 7.4% of SA and 32.5% of CNS. It is important to note that severe or generalized infections due to M(r) staphylococci should be treated with glycopeptide antibiotics such as vancomycin or teicoplanin from the very beginning, whereas chemotherapy of those with BOR strains may also be carried out with beta lactamase-stable beta lactam antibiotics. Comparing the results of this study with those of the first half of 1991, the respective proportion of M(r) staphylococci was significantly lower than 23.6% for SA and 47.6% for CNS recorded then. As compared with the foregoing period, however, these strains demonstrated increased resistance frequencies to gentamicin (from 81.3 to 90%), amikacin (from 35.4 to 69%), netilmicin (35.4 to 55%), and ciprofloxacin (56.2 to 64%). This is taken as an indication for the epidemic spread of a clone of resistant strains.

Anti-Bacterial Agents↗

Detection of somatic changes in human renal cell carcinomas with oligonucleotide probes specific for simple repeat motifs.

The purpose of our study was to detect somatic changes in renal cell carcinoma by multilocus fingerprinting. DNA fingerprints were generated from the DNA of normal and malignant renal tissue samples of 29 patients with nonhereditary kidney carcinoma by using oligonucleotide probes specific for simple repeat motifs such as (GTG)5, (CA)8, (GACA)4, or (TTAGGG)3. Each probe rendered a typical fingerprint pattern, because it is specific with respect to the target regions recognized in the genome. The restriction enzymes used were HinfI and HaeIII. Changed banding patterns were detected by using (GTG)5 in 20% of the tumors, in 20% for (CA)8 after HinfI digestion, and in 10% after HaeIII digestion. Even more informative probes were (GACA)4, showing 70% changes after HaeIII digestion, and (TTAGGG)3, with 80% changes after digestion with either enzyme. Since the simple repeat motifs recognized by (GACA)4 are localized on the short arms of the acrocentric chromosomes (13, 14, 15, 21, and 22), it is possible that sequences important for renal carcinogenesis are present in these regions. The observation of changes in regions to which (TTAGGG)3 hybridizes points to an involvement of DNA elements in telomeric sequence related regions in human kidney tumor formation.

Adult↗

[Bacterial endocarditis: microbiological diagnosis].

The microbiological laboratory can assist in diagnosis and therapy of bacterial endocarditis with the following parameters: cultivation and identification of the causative organism, sensitivity testing including assessment of the minimal bactericidal concentration (MBC) and testing of antibiotic combinations with checkerboard titrations and time-kill curves. Serum bactericidal titers, although controversial with respect to their utility in prognosing the clinical outcome, are regarded useful by some authorities but not by others. Antibiotic assays, mainly for aminoglycosides and vancomycin, serve to monitor antibiotic serum levels.

Anti-Bacterial Agents↗

The relationship between insight and control in obsessive-compulsive disorder: implications for the insanity defense.

In this paper the authors examine the relationship between insight and control in patients with obsessive-compulsive disorder (OCD) in an effort to better understand the concept of volitional control of behavior especially as it relates to changes in the insanity defense that were recommended by the American Psychiatric Association (APA), specifically that the volitional prong be dropped. Yale-Brown Obsessive Compulsive Scale ratings in 56 subjects with OCD were reviewed with specific attention to items measuring the patients' subjective sense of decreased volitional control over their compulsions and their insight into their behavior. No statistically significant correlation was found between the control over compulsions item and the insight item. The authors conclude that the experience of volitional control in patients with OCD is not significantly related to the level of insight they have into the irrationality of their behavior. The authors then review cognitive therapy literature and show that though cognition and volition may appear to be dissociated in some disorders, even in the absence of insight, a relatively gross measure of legally relevant cognitive disturbance, subtle cognitive changes can be identified in patients with seemingly purely volitional disorders such as OCD.

Adult↗

Expression of HER-2/neu in renal-cell carcinoma. Correlation with histologic subtypes and differentiation.

Twenty-four renal-cell carcinomas (RCC) and corresponding non-neoplastic kidney tissue were examined for amplification and expression of the HER-2/neu gene. Gene amplification was examined by slot-blot analysis, mRNA expression by in situ hybridization and Northern blot analysis, and protein expression by immunohistochemistry. Northern-blot analysis revealed lower expression of HER-2/neu mRNA in clear-cell (p less than 0.001) and compact (p less than 0.001) tumor subtypes, while chromophilic, chromophobic and tubulo-papillary subtypes did not show significant differences in HER-2/neu gene expression, as compared with non-neoplastic kidney tissues. HER-2/neu gene expression was not significantly associated with tumor stage. Low differentiation (G3) was associated with lower HER-2/neu gene expression, but the number of G3 cases was too small for statistical analysis. HER-2/neu gene amplification was not found in any of the tumors. The results of in situ hybridization and immunohistochemistry generally agreed with those of Northern-blot analysis. We conclude that HER-2/neu gene expression correlates with Thoenes' classification of RCC and may be inversely related to tumor differentiation; it is probably not involved in progression of RCC, in contrast to carcinomas of other locations (e.g. breast, ovary).

Blotting, Northern↗

Absence of interaction between tenoxicam and warfarin.

The influence of tenoxicam on plasma warfarin concentrations and on its anticoagulant effect has been studied in healthy volunteers. Tenoxicam did not alter the plasma warfarin concentration versus time profile. Treatment with it for 14 days had no effect on the average dose of warfarin required to maintain the prothrombin time within a specified range. The coumarin dose index, an indicator of warfarin sensitivity, remained unchanged during tenoxicam administration. The results demonstrate the lack of a clinically relevant effect of tenoxicam on warfarin-induced anticoagulation.

Adult↗

The human embryonic myosin alkali light chain gene: use of alternative promoters and 3' non-coding regions.

Recently we have found evidence that the human embryonic myosin alkali light chain (MLC1 emb) gene has two functional promoters and that its mRNAs exhibit heterogeneity in their 3'untranslated regions (UTR). To study this more in detail we have isolated and characterized the human MLC1emb gene. We focussed in particular on 2 kilobases of 5'flanking region and the alternative 3'UTRs. RNA primer extension and S1 mapping analyses revealed that the MLC1emb gene can indeed be driven either by a proximal or a distal promoter, both in fetal and adult cardiac tissue. These MLC1emb RNAs can contain either the proximal or distal 3'UTR. In contrast to this, in fetal as well as adult masseter muscle MLC1emb mRNA is predominantly transcribed from the proximal promoter and contains mainly the distal 3'UTR. These results explain the known heterogeneity of MLC1emb mRNAs. Finally, we present evidence that the murine MLC1emb gene also contains a functional distal promoter element which has hitherto been undetected.

Animals↗

An ABA and GA modulated gene expressed in the barley embryo encodes an aldose reductase related protein.

In most higher plants a period of desiccation is the terminal event in embryogenesis. Excised barley embryos acquire desiccation tolerance at a precise developmental stage and cDNA clones have been isolated which are temporally linked with desiccation tolerance. One such clone (pG22-69) with a putative gene product of 34 kd displays high structural homology to mammalian genes encoding an NADPH dependent aldose reductase involved in the synthesis of sorbitol. This first aldose reductase gene of plants is expressed constitutively during embryo maturation and is modulated by the plant hormones abscisic acid (ABA) and gibberellic acid (GA). Immunohistochemistry showed that the protein is preferentially expressed in tissues formed at early stages in embryogenesis. Measurements of enzymatic activity indicate that pG22-69 encodes an active aldose reductase. The finding of this reductase activity and the cloning of the corresponding gene supports the existence of a metabolic pathway in plants playing a role in the synthesis of osmolytes like sorbitol. The significance of this work is that genes of related structure and functions are being used in diverse organisms to fulfil stress related biological requirements.

Abscisic Acid↗

Educational programmes for infection control in Austria.

Educational aims and strategies (simply arousing awareness, sensitivity and understanding; and/or training in practical skills and knowledge; or the ability to teach infection control, and to convince those taught) depend on the target group. Infection control is part of the curriculum for students of medicine and other health care professions, and is included in course examinations. Postgraduate doctors may seek training on courses which are organized by the Hygiene Institute of the University of Vienna in co-operation with the Austrian Society of Hygiene, Microbiology and Preventive Medicine. Registered nurses may enroll in the Austrian Nurses' Association training scheme (6 weeks of theory with professional work for 2 years), leading to approval as Hygieneschwester/-pfleger. Postgraduate in-hospital education for all health-care professions occurs in many Austrian hospitals, with resources from Vienna and Linz. Hospital managements, health authorities and politicians are influenced via their own educational activities and via publications.

Austria↗