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Biomedical subjects

M Werner

Publications and source records attributed to M Werner.

At least 253 records · Page 14Linked to original sources
PubMed1994

Effect of analytic uncertainty of conventional and point-of-care assays of activated partial thromboplastin time on clinical decisions in heparin therapy.

The authors assessed the capability of assays of activated partial thromboplastin time (aPTT) for supporting clinical decision algorithms for heparin therapies of varying complexity. Blood samples were collected prospectively in three explicit management strategies from 100 sequential patients for whom heparin dosage was adjusted for therapeutic monitoring, femoral venous sheath removal after cardiac catheterization, or heparinization after thrombolytic therapy. In two- and three-way decision algorithms, conventional and point-of-care aPTT assays agreed with heparin assays in approximately two thirds of cases, and the two aPTT assays agreed in 80% or more of all cases. In six-way decision algorithms, the two aPTT assays agreed in only about half of all cases. The authors conclude that the reliability of point-of-care aPTT assays is similar to that of conventional assays. Both techniques can support two- and three-way decision algorithms but not some more complex patient classifications.

Algorithms↗
PubMed1994

Anaerobic pericarditis: case report and review.

Purulent pericarditis is uncommon and is rarely caused by anaerobic bacteria. We describe a 58-year-old man with purulent pericarditis secondary to infection with Bacteroides fragilis; the most likely source for the B. fragilis infection was subsequently found to be a ruptured appendix. His pericarditis eventually resolved after drainage of purulent fluid and treatment with antibiotics directed against B. fragilis. We also review 29 cases of anaerobic pericarditis previously reported in the English-language literature (we excluded those cases due to actinomyces). In 17 cases only anaerobic bacteria were isolated, while in 13 anaerobes were isolated with a mixture of facultative and/or aerobic bacteria. The cases were secondary to a contiguous focus of infection or occurred via hematogenous seeding. Treatment of both anaerobic pericarditis and purulent pericarditis due to aerobic bacteria entails adequate drainage and appropriate antibiotic therapy, and in all cases there should be a search for the source of the organism infecting the pericardium.

Appendicitis↗
PubMed1994

Influence of formalin fixation on the detection of cytomegalovirus by polymerase chain reaction in immunocompromised patients and correlation to in situ hybridization, immunohistochemistry, and serological data.

The possibility of detecting cytomegalovirus (CMV) in formalin-fixed tissues by polymerase chain reaction (PCR) was evaluated in necroposies from lung tissues in a total of 24 patients who either had received organ transplants or were immunocompromised. PCR using two different pairs of primers for amplification of the major immediate early antigen of CMV was performed on fresh tissues and tissues fixed for 24, 48, and 72 h in neutral buffered formalin and compared to immunohistochemistry (IHC) and in situ hybridization (ISH). The fresh tissues of nine patients with serological evidence for acute CMV infection were all positive for CMV by PCR. After formalin fixation, the majority of the patients failed to show distinct signals with one or both pairs of primers as measured by densitometry. In contrast to this, fresh tissues of 15 patients without signs of an acute CMV infection were found either negative or weakly positive by PCR. Using IHC or ISH, positive results were observed only in five of nine and four of nine patients with acute CMV infection, respectively. These data demonstrate that, if only formalin-fixed tissue is available, PCR for CMV detection should be performed using two pairs of primers and should be supported by IHC.

Adolescent↗
PubMed1994

A segment of mRNA encoding the leader peptide of the CPA1 gene confers repression by arginine on a heterologous yeast gene transcript.

The expression of the yeast gene CPA1, which encodes the small subunit of the arginine pathway carbamoylphosphate synthetase, is repressed by arginine at a translational level. CPA1 mRNA contains a 250-nucleotide-long leader which includes a 25-codon upstream open reading frame (uORF). Oligonucleotide site-directed mutagenesis of this uORF as well as sequencing of constitutive cis-dominant mutations has suggested that the leader peptide product of the CPA1 uORF is an essential negative element for repression of the CPA1 gene by arginine. In this work, a series of deletions affecting the regions 5' and 3' to the uORF in the leader sequence was constructed. The arginine-dependent repression of CPA1 was little affected in these constructions, indicating that these regions are not essential for the regulatory response. This conclusion was further supported by the finding that inserting the mRNA segment encoding the leader peptide sequence of CPA1 in the leader sequence of another gene, namely, GCN4, places this gene under arginine repression. Similarly, the behavior of fusions of the leader sequence of CPA1 with those of ARG4 or GAL10 confirmed that the regions of this leader located upstream and downstream from the uORF are dispensable for the regulation by arginine. Finally, a set of substitution mutations which modify the uORF nucleotide sequence while leaving unchanged the corresponding amino acid sequence was constructed. The mutations did not affect the repression of CPA1 by arginine. The data presented in this paper consequently agree with the conclusion that the leader peptide itself is the main element required for the translational repression of CPA1.

Amino Acid Sequence↗
PubMed1994

Suppression of yeast RNA polymerase III mutations by FHL1, a gene coding for a fork head protein involved in rRNA processing.

The FHL1 gene was isolated by screening for high-copy-number suppressors of conditional RNA polymerase III mutations. This gene is unique on the yeast genome and was located close to RPC40 and PRE2 on the right arm of chromosome XVI. It codes for a 936-amino-acid protein containing a domain similar to the fork head DNA-binding domain, initially found in the developmental fork head protein of Drosophila melanogaster and in the HNF-3 family of hepatocyte mammalian transcription factors. Null mutations caused a severe reduction in growth rate and a lower rRNA content that resulted from defective rRNA processing. There was no detectable effect on mRNA splicing. Thus, the Fhl1p protein plays a key role in the control of rRNA processing, presumably by acting as a transcriptional regulator of genes specifically involved in that process. Moreover, mutants carrying the RNA polymerase III mutations were slightly defective in rRNA processing. This accounts for the isolation of FHL1 as a dosage-dependent suppressor and suggests that rRNA processing depends on a still-unidentified RNA polymerase III transcript.

Amino Acid Sequence↗
PubMed1994

[Hodgkin lymphomas ar negative with regard to bcl-2/JH gene rearrangement, but partly express BCL-2 protein: analysis of 83 cases from the German Hodgkin Trial].

Conflicting data on the presence of bcl-2/JH gene rearrangement and BCL-2 protein expression in Hodgkin's disease (HD) have been reported. To find out the reason for these differences, well characterized cases from the German National Trial were examined by PCR for the bcl-2 gene rearrangement and immunohistochemically for BCL-2 protein expression. No bcl-2/JH rearrangement could be detected among the HD analyzed from paraffin sections, as well as another 24 cases of HD investigated in fresh tissue. Contrasted with this, immunohistochemistry demonstrated BCL-2 protein expression in all types of HD. In conclusion, our results suggest that the bcl-2/JH gene rearrangement does not play a role in HD, but BCL-2 protein is frequently expressed by RS/H cells of non-lymphocyte predominance subtypes.

Antigens, CD↗
PubMed1994

Increased levels of a 21-kDa protein in the circulation of tumor-bearing patients.

A novel non-ras 21-kDa protein (p21) was detected in sera of cancer patients by enzyme-linked immunosorbent assay (ELISA), using polyclonal anti-p21 antibodies. While only 4.6% of the healthy donors (n = 43) showed p21 serum levels higher than the mean +/- 2 SD of the normal group, 33 to 80% of the cancer patients (n = 94) with various tumors were positive in the ELISA test. In particular, patients with malignant lymphoma, urogenital, and gastrointestinal tumors had a 2.8- to ninefold increase in p21 serum levels. Elevated serum levels were also found in patients with benign prostatic hyperplasia (3.2-fold increase). In 17 out of 22 patients with urogenital tumors, changes in serum p21 levels correlated with the clinical course of the disease. In 15 patients, a favorable response to therapy was correlated with a decline in serum p21 level. Two patients with renal cell carcinoma showed increased or persistently high levels of p21 after surgery and were subsequently found to have distant metastases. Expression of p21 in ten renal cell carcinoma tissues was determined by Western blotting. There was a trend toward a higher content of p21 in the less-differentiated tumor tissues. In conclusion, p21 may be a useful indicator in monitoring the outcome of treatment in patients with various malignant tumors. In patients with renal cell carcinoma, p21 serum levels may be of particular importance because no other tumor marker is available.

Adult↗
PubMed1993

[Acute cytomegalovirus gastritis after kidney transplantation. Its diagnosis by the polymerase chain reaction, antigenemia assay and immunohistochemistry].

To diagnose possible cytomegalovirus (CMV) infection in a 64-year-old man after renal transplantation, polymerase chain reaction (PCR), pp65 antigenaemia assay (pAA) and virus isolation in cell culture were routinely performed on a weekly basis. The PCR obtained virus DNA in peripheral blood lymphocytes for the first time in the fifth week. Two weeks later the patient complained of feeling unwell with abdominal pain and vomiting on eating. Two days later he developed a fever up to 38 degrees C and nocturnal sweats. Gastroscopy revealed marked antral gastritis which histologically showed typical cytomegalic "owl-eye" cells. The pAA was clearly positive and the cell culture started in the fifth week now showed a cytopathogenic effect. CMV gastritic having been diagnosed treatment consisted of 175 mg ganciclovir intravenously twice daily for 10 days. He became symptom-free after two days. The only side effects were thrombocytopenia down to 67,000/microliters and a rise in transaminase activities, changes which regressed later. To ensure early diagnosis and treatment of any CMV infection, specific virus diagnostic tests should be routinely undertaken after transplantation of organs from CMV-positive persons into CMV-negative patients.

Acute Disease↗
PubMed1993

Interaction between a complex of RNA polymerase III subunits and the 70-kDa component of transcription factor IIIB.

A system that detects the formation of complexes between different proteins by linking them to separate domains of the GAL4 transcription activator protein has been used to study protein-protein interactions between four essential and unique subunits of yeast RNA polymerase III (C82, C53, C34 and C31), the 70-kDa component of the initiation transcription factor IIIB (TFIIIB70) and the TATA-binding protein. We found that C82, C34, and C31 are able to combine with each other in vivo and that C34 interacts with TFIIIB70. These results suggest that C34 and TFIIIB70 are specificity determinants of the RNA polymerase III-TFIIIB interaction.

DNA-Binding Proteins↗
PubMed1993

Comparative clinical evaluation of biochemical and genomic tumor markers.

The clinical utilities of established biochemical tumor markers and of emerging genomic markers are compared by six formal criteria: [1] tests negative in health or benign disease, [2] produced exclusively by specific tumor cells, [3] present frequently in the targeted malignancy, [4] detectable in occult disease, [5] degree of expression reflects tumor burden and prognosis, and [6] degree of expression correlates with therapeutic result. Evaluation of eight widely accepted marker systems combining a biochemical indicator with a specific cancer, on the one hand, and five representative genomic marker-target combinations involving chromosomal translocation, gene amplification and mutation, on the other hand, produces three main conclusions: First, specified applications are sufficiently well documented for the best biochemical markers to now tailor analytical performance goals to these uses. Second, further clinical trials of genomic markers are needed to document the useful linkage of specific indicators with specific clinical problems. Third, the different profiles of marker characteristics defining the two classes of indicators suggest some mutually complementary uses.

Animals↗
PubMed1993

[Integrated health promotion in business: starting problems and proposed solutions].

Integrated worksite health promotion takes into account as well the demands of employees as those of the enterprises and at the same time applies to both, health behaviour and operational conditions of the companies. It is not restricted to a singular action but makes a continuous effort to promote the health of employees as an integrated part of employers' planning and politics. Apprehension between employers and employees seems to be one of the key obstacles of worksite health promotion. Therefore both sides have to keep negotiating to what extent health promotion has to improve efficiency of employees in respect to enterprises or how far operational conditions have to be adjusted to suit the well-being of personnel. A possible solution to solve this dilemma would be a widening of the conception of efficiency and incorporating of long-term thinking.

Health Behavior↗
PubMed1993

Hypoplastic myelodysplastic syndrome: incidence, morphology, cytogenetics, and prognosis.

The present study, based upon the retrospective evaluation of 352 patients with primary myelodysplastic syndrome (pMDS), revealed hypoplastic MDS in 42 patients (11.9%). Median age is similar in hypo- and normo-/hypercellular MDS (72.6 versus 70.7 versus 72.4 years). Hypoplastic MDS occurred significantly more often in women compared with normo- and hypercellular MDS. Sequential biopsies were performed in 14 patients, showing a persistence of hypoplasia over a period of up to 43 months. The proportion of patients showing mesenchymal reaction, especially an increase of mast cells, was significantly higher in hypoplastic MDS, whereas dysplastic features of hematopoiesis occurred less frequently and were of lower grade in comparison to normo-/hyperplastic MDS. Among the subgroup with hypoplastic bone marrow, the classification according to FAB criteria revealed 28 patients with RA (66.7%), three with RARS (7.1%), and eight with RAEB (19.0%), as well as one patient each with RAEB-T and CMMol (2.4% each), and one case which had to be reckoned among the category of unclassifiable MDS (2.4%). Median survival was 21.8 months for hypoplastic MDS, 26.9 months for normoplastic MDS, and 14.2 months for hyperplastic MDS. During follow-up, 14 patients (33%) with hypoplastic MDS developed acute nonlymphatic leukemia. Although not a constant finding, karyotype abnormalities involving particularly chromosome 7 seem to be associated with hypoplastic MDS. The results confirm the existence of a hypoplastic variant of MDS which seems to more frequently affect female patients, and which requires bone marrow biopsy for its accurate diagnosis.

Adult↗
PubMed1993

Evidence from molecular genetic and cytogenetic analyses that bone marrow histopathology is reliable in the diagnosis of chronic myeloproliferative disorders.

The reliability of histopathological diagnosis in bone marrow specimens from patients with chronic myeloproliferative disorders (CMPD) was evaluated by correlating the histological findings with molecular genetic and cytogenetic analyses of the Ph1-translocation. A rearrangement of m-bcr was detected only in patients (28/30) diagnosed histologically as chronic myeloid leukemia (CML). This finding was supported by the presence of a Ph1-chromosome in 24/26 patients with CML examined. All the patients with other types of CMPD, including polycythemia vera (PV), primary thrombocythemia (PTH) and chronic megakaryocytic-granulocytic myelosis (CMGM), as well as those with unclassifiable CMPD (CMPD.UC) were Ph1-negative (n = 38). The histopathological discrimination of CML from Ph1-negative varieties of CMPD was also reliable for patients with myelofibrosis complicating CML, CMGM and CMPD.UC. The results demonstrate that bone marrow histopathology allows a reliable diagnosis of CML. This is in contrast with hematological data such as high platelet counts which show considerable overlapping in the various forms of CMPD.

Adult↗
PubMed1993

Different cytogenetic findings in two clinically similar leukaemic dogs.

A 4-month-old German Shepherd puppy and a 7-year-old Boxer dog, in which a clinical diagnosis of acute lymphoblastic leukaemia had been made, were investigated cytogenetically. In the puppy a diploid karyotype was found, but the malignant clone in the Boxer was characterized by an extra metacentric chromosome, apparently formed as the result of a Robertsonian translocation of two chromosomes 1. These findings are discussed against the background of similar cases reported in the literature. Possibly, different types of acute canine leukaemic disease, occurring at different ages, can be distinguished by cytogenetic evaluation.

Age Factors↗