Search PubMed⌕ Search

Biomedical subjects

K Meyer

Publications and source records attributed to K Meyer.

At least 163 records · Page 9Linked to original sources
PubMed1996

Temperature-sensitive phenotype of the human parainfluenza virus type 3 candidate vaccine strain (cp45) correlates with a defect in the L gene.

We have previously demonstrated that the temperature sensitivity of a human parainfluenza virus type 3 (HPIV-3) candidate vaccine strain (cp45), which is currently under evaluation in humans, is associated with poor transcriptional activity of the virus at the nonpermissive temperature (R. Ray, K. Meyer, F. Newman, and R. B. Belshe, J. Virol. 69:1959-1963, 1995). In this study, the temperature sensitivity of cp45 virus was further investigated by the complementation of a specific gene function. CV-1 cells were transfected with cloned genes from wild-type HPIV-3 encoding the large protein (L), phosphoprotein (P), and nucleocapsid protein (NP), alone or together, for the expression of biologically active proteins. Only cells expressing the L gene were able to rescue cp45 replication when incubated at the nonpermissive temperature (39.5 degrees C), whereas cells transiently expressing NP or P were incapable of rescuing the virus. The virus titers obtained following complementation of the L protein were 190 to 2,300 PFU/ml of culture medium, compared with the undetectable growth of the cp45 temperature-sensitive mutant at the nonpermissive temperature. Rescued progeny virus still maintained the temperature-sensitive phenotype. Results from this study suggest that the temperature sensitivity of the cp45 candidate vaccine strain is associated primarily with L-protein function and that the defect can be complemented by transient expression of the wild-type protein. This study underscores the importance of the L protein in RNA polymerase activity and its critical role in virus replication.

Animals↗
PubMed1996

Hepatitis C virus core protein cooperates with ras and transforms primary rat embryo fibroblasts to tumorigenic phenotype.

We have previously demonstrated that hepatitis C virus (HCV) core protein regulates cellular protooncogenes at the transcriptional level; this observation implicates core protein in the alteration of normal hepatocyte growth. In the present study, the transforming potential of the HCV core gene was investigated by using primary rat embryo fibroblast (REF) cells which were transfected with or without cooperative oncogenes. Integration of the HCV core gene resulted in expression of the viral protein in REF stable transformants. REF cells cotransfected with HCV core and H-ras genes became transformed and exhibited rapid proliferation, anchor-independent growth, and tumor formation in athymic nude mice. Results from these studies suggest that the core protein plays an important role in the regulation of HCV-infected cell growth and in the transformation to tumorigenic phenotype. These observations suggest a possible mechanism for this viral protein in the pathogenesis of hepatocellular carcinoma in HCV-infected humans.

Animals↗
PubMed1996

Improved flow cytometric identification of myelopoiesis by the simultaneous labelling with CD13, CD14 and CD66 monoclonal antibodies.

The aim of the present study was to increase our knowledge of myelopoiesis evaluated by flow cytometry. We therefore designed a triple-marker assay employing monoclonal antibodies against the CD13 (immature), the CD14 (monocytic), and the CD66 (mature myeloid) antigens using three-colour immunofluorescence. In normal donor bone marrow the assay enables simultaneous identification of immature (CD13+, CD14-, CD66-), intermediate (CD13+, myelopoietic differentiation stages through the exclusion of CD14+ monocytic cells. In the diagnosis and longitudinal follow-up of AML patients the assay was of value in the fast determination of remission state. In MDS, the immature myeloid component could be distinguished in patients defined according to the FAB classification with the possibility of identifying aberrant phenotypes, the assay should also be of interest in other myeloproliferative disorders. Moreover, because it is easy to perform, time-saving, and yields comparable results to single antibody reactivity controls, it can replace more tedious and less-informative flow cytometric immunophenotyping procedures.

Acute Disease↗
PubMed1996

Characterization of glucuronidated phase II metabolites of the immunosuppressant cyclosporine in urine of transplant patients using time-of-flight secondary-ion mass spectrometry.

The immunosuppressant, cyclosporine, is metabolized in the liver and small intestine to > 30 metabolites. Metabolism and immunosuppressive and toxic potentials of the metabolites are still unclarified. Therefore, search and determination of new metabolites remain an important part of cyclosporine research. In this study, cyclosporine metabolites were determined in 42 urine samples of transplant patients using time-of-flight secondary-ion MS. Besides the known metabolites of phase I and phase II, other groups of new phase II metabolites were detected, and most of them were identified as glucuronidated phase I metabolites. All metabolites were found in the urine of heart, kidney, and bone marrow graft patients, with frequencies in the range of 74% and 12%. The most intensive group of these metabolites was also detected in a HPLC fraction, together with the known glucuronidated AM1c. The concentration of this new metabolic group could be estimated to < or = 5/ml. In conclusion, this work demonstrated that time-of-flight secondary-ion MS is a powerful tool in pharmacological investigations. Furthermore this study showed that phase II metabolism is an important metabolic pathway of cyclosporine in transplant patients.

Animals↗
PubMed1995

Transcriptional regulation of cellular and viral promoters by the hepatitis C virus core protein.

The genomic region encoding the hepatitis C virus (HCV) core protein was cloned into a mammalian expression vector to study its role on the transcriptional regulation of cellular proto-oncogene and viral promoters. Using a transient transfection assay in human hepatocellular carcinoma (HepG2) cells, we demonstrate that the HCV core protein activates the human c-myc, Rous sarcoma virus long terminal repeat (LTR), and simian virus 40 (SV40) early promoters; and suppresses the c-fos promoter and human immunodeficiency virus type 1 (HIV-1) LTR activity. The transcriptional regulation of cellular proto-oncogenes by the HCV core protein suggests possible involvement of the core protein in the deregulation of normal hepatocyte growth and hepatocarcinogenesis.

3T3 Cells↗
PubMed1995

Preserved merosin M-chain (or laminin-alpha 2) expression in skeletal muscle distinguishes Walker-Warburg syndrome from Fukuyama muscular dystrophy and merosin-deficient congenital muscular dystrophy.

The merosin M-chain (or laminin-alpha 2) is one of three subunits of laminin-2 which is highly expressed in striated muscle and peripheral nerve. Complete lack of laminin-alpha 2 expression in skeletal muscle is the hallmark of one form of congenital muscular dystrophy which is characterized by dysmyelination of the central nervous system (CNS), links to chromosome 6q2 and is common among Caucasians. Laminin-alpha 2 expression was also found to be significantly reduced in Fukuyama congenital muscular dystrophy which links to chromosome 9q3. We report consistently preserved laminin-2 expression, including laminin-alpha 2, as detected by immunofluorescence in skeletal muscle from five patients with Walker-Warburg syndrome which is characterized by congenital muscular dystrophy and, in addition, type II lissencephaly or pachygyria, defective CNS myelination, and ocular dysgenesis. These findings show that in spite of partial phenotypic overlap between Fukuyama CMD and Walker-Warburg syndrome the two disorders are nosologically separate disease entities. They also exclude that Walker-Warburg syndrome is allelic to the common form of congenital muscular dystrophy with laminin-alpha 2 deficiency.

Antibodies↗
PubMed1995

Relationship between ventilatory threshold and onset of ischaemia in ECG during stress testing.

UNLABELLED: The study was carried out to determine the relationship between ventilatory threshold and the onset of ischaemia, as shown on the ECG (horizontal and/or descending ST depression of 0.05 mV, on average). Twenty-seven male patients (aged 58 +/- 7 years) with angiographically documented coronary artery disease (CAD) were assessed by cardiopulmonary exercise testing without medication. Oxygen uptake (VO2), heart rate (HR), rate-pressure-product (RPP) and blood lactate were measured and/or calculated every 30 s during exercise. In addition, 10 patients, comparable with the above group, were examined to find out the acute effects of isosorbide dinitrate (ISDN) at ventilatory threshold in relation to ischaemic threshold. The first cardiopulmonary exercise test was carried out without medication, the second 1 h later with 5 mg ISDN, taken sublingually 30 min before the test. RESULTS: (means, SD): (1) The mean ventilatory threshold preceded the ischaemic threshold in relation to exercise capacity (48 +/- 14 vs 55 +/- 20 watts; P < 0.05), VO2.kg-1 (10.0 +/- 2.2 vs 12.0 +/- 2.9 ml.kg-1.min; P < 0.05), HR (93 +/- 15 vs 100 +/- 16.min-1; P < 0.01), RPP (15095 +/- 4424 vs 17166 +/- 5245; P < 0.01) and blood lactate (1.28 +/- 0.53 vs 1.44 +/- 0.60 mmol.l-1; P < 0.05). (2) This relationship was observed more often in the subgroup of patients with angina during cardiopulmonary exercise testing or with myocardial infarction or with three-vessel disease than in patients without angina or infarction or with one- and two-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Characterization of a live, attenuated human parainfluenza type 3 virus candidate vaccine strain.

Characterization of a temperature-sensitive and live, attenuated human parainfluenza type 3 virus strain (cp45) grown at a permissive temperature (32 degrees C) suggested that the virus efficiently multiplies in cell lines and retains antigenic and functional properties of the envelope glycoproteins. When grown at a nonpermissive temperature (39.5 degrees C), the cp45 virus exhibited poor replication; however, shifting to a permissive temperature allowed virus growth. Although at a nonpermissive temperature virus polypeptide synthesis was significantly reduced, the hemagglutinin-neuraminidase and fusion glycoproteins were transported to cell surfaces and retained their characteristic biologic activities. Studies on mRNA synthesis from the P protein gene suggested a poor transcriptional activity of the cp45 virus at a nonpermissive temperature. Results from this study indicate that the temperature sensitivity of cp45 virus is related to altered transcriptional activity and a marked reduction in virus polypeptide synthesis.

Antibodies, Monoclonal↗
PubMed1995

Interaction of eukaryotic initiation factor eIF-4B with a picornavirus internal translation initiation site.

We studied the interaction of cellular proteins with the internal ribosome entry site (IRES) of foot-and-mouth disease virus by UV cross-linking and observed specific binding of a 80-kDa protein contained in cytosolic HeLa cell extract and in rabbit reticulocyte lysate. Binding of the protein was dependent on the presence of ATP. Immunoprecipitation with eIF-4B antiserum revealed that the protein is identical to the initiation factor eIF-4B. Deletions in the 3' part, but not in the 5' part, of the IRES interfered with UV cross-linking, indicating that the binding site of eIF-4B is located close to the end of the element. Attempts to separate ribosome-associated from non-ribosome-associated protein fractions of cytosolic cell extracts led to the loss of cross-linking activity. This finding suggests that additional protein factors contribute to this interaction of eIF-4B with the IRES of foot-and-mouth disease virus.

Adenosine Triphosphate↗
PubMed1995

Immune responses to plasmid DNA encoding the hepatitis C virus core protein.

Hepatitis C virus (HCV) is a major causative agent of parenterally transmitted non-A, non-B hepatitis. The genomic region encoding the virion-associated core protein is relatively conserved among HCV strains. To generate a DNA vaccine capable of expressing the HCV core protein, the genomic region encoding amino acid residues 1 to 191 of the HCV-1 strain was amplified and cloned into an eukaryotic expression vector. Intramuscular inoculation of recombinant plasmid DNA into BALB/c mice (H-2d) generated core-specific antibody responses, lymphoproliferative responses, and cytotoxic T-lymphocyte activity. Our results suggest that the HCV core polynucleotide warrants further investigation as a potential vaccine against HCV infection.

3T3 Cells↗
PubMed1995

A comparison of the dynamic pedobarograph and EMED systems for measuring dynamic foot pressures.

The purpose of this study was to compare the peak pressure and peak force values obtained from two pressure assessment systems, the Dynamic Pedobarograph and the EMED SF. Twenty-one individuals with a mean age of 31.6 years walked barefoot over both systems using a two-step data collection protocol. Peak plantar pressures and peak vertical force values were measured under the heel, central forefoot, hallux, and entire foot for both systems. The results of this study demonstrated that the EMED SF system produced larger peak pressures under the central forefoot and hallux. The Pedobarograph, on the other hand, produced greater pressures under the heel and entire foot. With respect to peak vertical forces, the Pedobarograph showed significantly greater values under the heel and central forefoot compared with the EMED SF, but were significantly lower under the hallux and entire foot.

Adult↗
PubMed1995

Zingiber officinale (ginger) used to prevent 8-Mop associated nausea.

Patients undergoing photopheresis are required to ingest the drug 8-MOP as part of their treatment. This drug causes nausea as a side effect. Ginger taken prior to 8-MOP may substantially reduce this side effect. This study compared patients' nausea when taking 8-MOP with and without ginger.

Adult↗
PubMed1995

Smith-Lemli-Opitz syndrome diagnosed by using time-of-flight secondary-ion mass spectrometry.

We describe a rapid and sensitive method involving time-of-flight secondary-ion mass spectrometry (TOF-SIMS) for specific laboratory diagnosis of the Smith-Lemli-Opitz syndrome, which is characterized by massive (approximately 1000-fold) accumulation of the biosynthetic cholesterol precursor 7-dehydrocholesterol. Minute amounts of blood (1-50 microL) were extracted with n-hexane, and aliquots were analyzed by TOF-SIMS. 7-Dehydrocholesterol and its isomers were detected at 491.3 mass units ([M + 107Ag]+) and cholesterol at 495.3 mass units ([M + 109Ag]+). Quantitation of 7-dehydrocholesterol and cholesterol was achieved after saponification and addition of stigmasterol as internal standard. Whereas 7-dehydrocholesterol and isomeric dehydrocholesterol were not detectable in controls, the patients revealed concentrations ranging between 0.84 and 1.25 mmol/L. Comparison with results obtained by gas chromatography indicated that quantitation by TOF-SIMS yielded the sum of 7-dehydrocholesterol, isomeric dehydrocholesterol II, and sterol III, the latter two also being increased in the patients. Consistent with quantitation by gas chromatography, the cholesterol concentrations in the patients ranged between 1.54 and 2.12 mmol/L (controls: 6.10 +/- 1.37 mmol/L).

Cholesterol↗
PubMed1995

The 'Learnmore' project: information acquisition solutions for the long-term care information system.

Research and development efforts on Long Term Care (LTC) information systems are only beginning to appear in the literature. For the past two years, a small, interdisciplinary team of researchers (the Learnmore Team) have designed information solutions to information acquisition problems in LTC systems. This paper provides an overview of the Learnmore Team's proposed solutions to acquisition problems experienced by end-users (clinicians, students, and patients) and human experts. Solutions addressing information acquisition costs of integrated expert systems are also discussed. Critical issues and experiences gained during the development of these solutions are presented.

Expert Systems↗
PubMed1994

A protein phosphatase 2C involved in ABA signal transduction in Arabidopsis thaliana.

The plant hormone abscisic acid (ABA) mediates various responses such as stomatal closure, the maintenance of seed dormancy, and the inhibition of plant growth. All three responses are affected in the ABA-insensitive mutant abi1 of Arabidopsis thaliana, suggesting that an early step in the signaling of ABA is controlled by the ABI1 locus. The ABI1 gene was cloned by chromosome walking, and a missense mutation was identified in the structural gene of the abi1 mutant. The ABI1 gene encodes a protein with high similarity to protein serine or threonine phosphatases of type 2C with the novel feature of a putative Ca2+ binding site. Thus, the control of the phosphorylation state of cell signaling components by the ABI1 product could mediate pleiotropic hormone responses.

Abscisic Acid↗
PubMed1994

Peptide immunogen mimicry of putative E1 glycoprotein-specific epitopes in hepatitis C virus.

Hepatitis C virus (HCV) accounts for most cases of acute and chronic non-A and non-B hepatitis with serious consequences that may lead to hepatocellular carcinoma. The putative envelope glycoproteins (E1 and E2) of HCV probably play a role in the pathophysiology of the virus. In order to map the immunodominant domains of the E1 glycoprotein, two epitopes from amino acid residues 210 to 223 (P1) and 315 to 327 (P2) were predicted from the HCV sequence. Immunization of mice with the synthetic peptides conjugated to bovine serum albumin induced an antibody response, and the antisera immunoprecipitated the E1 glycoprotein (approximately 33 kDa) of HCV expressed by recombinant vaccinia virus. A panel of HCV-infected human sera was also tested with the synthetic peptides by enzyme-linked immunosorbent assay for epitope-specific responses. Of 38 infected serum samples, 35 (92.1%) demonstrated a spectrum of reactivity to the P2 peptide. On the other hand, only 17 of 38 (44.7%) serum samples were reactive to the P1 peptide. Strains of HCV exhibit a striking genomic diversity. The predicted P1 epitope showed localization in the sequence-variable region, and the P2 epitope localized in a highly conserved domain. Results from this study suggest that the E1 glycoprotein of HCV contains at least two potential antigenic epitopes. Synthetic peptides corresponding to these epitopes and antisera to these peptides may serve as the monospecific immunological reagents to further determine the role of E1 glycoprotein in HCV infection.

Amino Acid Sequence↗
PubMed1994

Relationship between exercise tolerance, hemodynamics at rest and during exercise and ejection fraction, and their prognostic relevance in asymptomatic postinfarction patients.

In 309 postmyocardial infarction patients (age 40 +/- 7.7 years) without persistent ischemia there is only a weak correlation between ejection fraction (EF) and exercise tolerance (r = 0.45, p < 0.01), and between EF and maximum cardiac output (CO; r = 0.41, p < 0.01) and maximum pulmonary capillary wedge pressure (PCWP; r = -0.32, p < 0.001). The same was true for exercise tolerance and maximum PCWP (r = -0.53, p < 0.001). A big scattering of individual values could be observed. Although we found a high positive correlation between maximum CO and exercise tolerance (r = 0.80, p < 0.001), in individual cases a low CO could be related to high exercise tolerance and vice versa. In the multivariate analysis, only the heart volume/kg body weight and maximum PCWP could be shown to be of independent prognostic importance for survival and/or mortality in the following years (chi 2 = 5.9, p < 0.015 and chi 2 = 7.2, p < 0.007, respectively).

Adult↗