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Biomedical subjects

K Meyer

Publications and source records attributed to K Meyer.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

Cardiopulmonary exercise capacity in healthy normals of different age.

Sixty-nine healthy normals from the 3rd to the 6th decade were stressed to exhaustion by means of a cardiopulmonary exercise test on a bicycle ergometer. Peak VO2, VCO2 and ventilation differed significantly between the four decades: peak VO2 (mean +/- SD) was 3,393 +/- 516; 3,061 +/- 444; 2,817 +/- 801 and 2,589 +/- 687 ml/min (p < 0.001). The mean value for respiratory gas exchange ratio (R) at ventilatory threshold (VT) was 0.86 and for ventilatory equivalent O2 (EqO2) 0.24. Mean VO2 at VT was 1,662 +/- 521; 1,462 +/- 308; 1,474 +/- 559 and 1,268 +/- 232 ml/min (p < 0.05). The VO2 of the four age groups at VT was between 47 and 49% of peak VO2 (n.s.), and both parameters correlated significantly (r = 0.67, p < 0.001). The average increase of VO2 in relation to work rate (ml/W/min) was 11.5 +/- 1.2 for the total exercise and was below VT lower (9.4 +/- 1.9) than above VT (12.9 +/- 1.2) (p < 0.001).

Adult

Genetic parameters for milk production of Australian beef cows and weaning weight of their calves.

Estimates of covariance components were obtained for milk production of beef cows, measured by the weigh-suckle-weigh method, and weaning weight and preweaning growth of their calves for a herd of Polled Herefords and a herd of a multibreed synthetics, so-called Wokalups. Analyses were carried out by restricted maximum likelihood fitting an animal model incorporating both direct and maternal genetic and permanent environmental effects and allowing for the direct-maternal covariances. Average 14-h milk yield was 3.6 kg for Herefords and 4.9 kg for Wokalups and heritabilities were .12 and .08, respectively. Treating preweaning gain of the calf as a trait of the cow, estimates of the additive genetic and permanent environmental correlations between preweaning gain and milk yield were higher for Herefords (.73 and 1.00, respectively) than for Wokalups (.53 and .77). Bivariate analyses of milk production (treated as a trait of the cow) and weaning weight (treated as a trait of the calf) showed virtually no direct additive genetic, direct permanent environmental, or phenotypic association between the two traits but identified strong correlations between direct effects for milk yield and maternal effects for weaning weight. The estimate of the direct-maternal genetic correlation between milk yield and weaning weight was .80 for both breeds, and the estimated correlation between direct, permanent environmental effects for milk yield and maternal, permanent environmental effects on weaning weight was unity for Herefords and .89 for Wokalups. Results indicate that milk production is the main determinant of maternal effects on the growth of beef calves with breed differences in the importance of maternal effects largely attributable to differences in milk production.

Analysis of Variance

Antisense inhibition of myeloperoxidase increases the sensitivity of the HL-60 cell line to vincristine.

Myeloperoxidase (MPO), a heme-peroxidase found in the HL-60 myeloblastic cell line, is involved in vincristine (VCR) metabolism and the inactivation of this drug. We have examined whether decreased MPO activity correlated with increased sensitivity to VCR toxicity in myeloid leukemia cells. We have used MPO antisense RNA to reduce 60% of the MPO activity in the HL-60 cells. The MPO-deficient HL-60 cell line, C15, was significantly more sensitive to VCR than the parental MPO-positive cell line. Both cell lines were negative for P170-glycoprotein expression. Conversely, an MPO-positive C15 subclone was more resistant to VCR than the MPO-deficient C15 cell line. No significant differences in cytotoxic effects were observed between MPO-positive and MPO-deficient cells, following treatment with either daunorubicin or actinomycin D, two multidrug resistance-related drugs. These results strongly support an important role for MPO in VCR resistance in HL-60 cells. Antisense manipulation of the MPO content of myeloid cells could be of potential interest in leukemia treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem

Outpatient protocol for biofeedback therapy of pelvic floor outlet obstruction.

Pelvic floor outlet obstruction is a rare cause of severe constipation. Anal myectomy, subtotal colectomy, and medical therapy have limited success. The purpose of this study was to develop a short outpatient treatment using biofeedback techniques. Nine patients with severe constipation and straining resulting from pelvic floor outlet obstruction underwent complete investigation of the pelvic floor musculature and anal sphincter mechanism. Patients were unable to expel a 60-cc rectal balloon and had nonrelaxing puborectalis on defecography. The treatment protocol utilized anal surface electromyography to document improper straining and retrain pelvic floor muscles to relax during defecation. Sensory retraining with a rectal balloon, behavioral relaxation techniques, and defecation of simulated stool using a 120-cc Metamucil (Procter & Gamble, Cincinnati, OH) slurry in the rectum allowed re-establishment of normal defecation in all nine patients. Repeat training was required in three patients during follow-up. Treatment of pelvic floor outlet obstruction with outpatient retraining techniques is possible.

Adult

Mouse erythrocyte rosette formation with malignant human B-lymphocytes re-evaluated: still a useful marker for differentiating mature B-cell malignancies.

We have re-evaluated mouse rosette formation (MRF) as a marker for B-CLL by estimating the fraction of mouse rosette forming B-lymphocytes (identified by CD20 monoclonal antibodies) in normal donors and malignant CD20+ cell proliferations (ALL, AML, B-NHL, B-HCL and B-CLL). Whereas this ratio was increased in B-CLL, all other CD20 positive malignancies showed mean ratios of less than 0.1. As part of a Danish multi-centre study, we furthermore prospectively analysed 86 patients and found that the mouse/CD20 ratio divided the 78 patients with monoclonal B-cell populations suspected of B-CLL in two distinct groups. In the low ratio group, three patients were categorized as leukaemized B-NHL and one as PLL. The remaining three patients with low ratio were clinically and immunologically (by SmIg density and CD5 expression) B-CLL patients suggesting a frequency of MR-negative B-CLLs of approximately 5%. In the high ratio group two of 70 patients were diagnosed as B-NHLs. Thirdly, MRF was a valuable parameter in patients, where transformation of disease is suspected, since it preceded clinical changes by several months. Thus, MRF is still a useful marker in the age of monoclonal antibodies.

Adult

Sire x herd interactions for weaning weight in beef cattle.

Weaning weight records of 44,357 Australian Angus calves produced by 1,020 sires in 90 herds were used to evaluate the importance of sire x herd interactions. Models fitted fixed effects of contemporary group (herd-year-date of weighing subclass), sex, calf age, and dam age and random effects of sire or of sire and sire x herd interaction using REML. Effects of standardizing the data, including sire relationships and including dam maternal breeding values (MBV) as a covariate were also investigated. Sire x herd interactions were found (P less than .05) in all cases and, in the most complete model, accounted for 3.3% of phenotypic variance. Across-herd heritabilities ranged from .19 to .28. Differential nonrandom mating among herds seemed to occur in the data. Significant sire x herd effects were observed for dam MBV, and adjustment for dam MBV yielded the smallest estimates of interaction variance and across-herd heritability. If sire x herd interactions were due only to genotype x environment interaction, within-herd heritabilities would range from .33 to .49. These estimates are larger than previously reported estimates. Thus, unreported environmental effects common to progeny of individual sires may also be involved in the observed interaction but could not be disentangled from true genotype x environment interaction effects using these data. Results of these analyses suggest that some accommodation of sire x herd interaction effects on weaning weight may be needed in beef cattle genetic evaluations, but a compelling case for development of herd-specific breeding value prediction cannot be made.

Animals