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Biomedical subjects

M Hayden

Publications and source records attributed to M Hayden.

At least 19 recordsLinked to original sources
PubMed1995

Expression in Escherichia coli and affinity purification of a CKS-troponin I fusion protein.

The human cardiac troponin I gene was subcloned and expressed at high levels in Escherichia coli as a fusion protein to CMP-KDO synthetase (CKS). Expression levels of the CKS-troponin I fusion were 8% of total cellular protein 4 h after induction with IPTG. The fusion was expressed primarily as an insoluble protein as shown by SDS-PAGE analysis. Expressed CKS-troponin I fusion from a crude lysate was antigenic against anti-CKS and anti-troponin I monoclonal antibodies in Western blots. The fusion was affinity-purified over a TnC affinity column using a urea-solubilized extract of a crude cell lysate. Serial dilutions of crude soluble extracts of the troponin I fusion were assayed in several microparticle enzyme immunoassays and found to exhibit similar immunogenic responses relative to cardiac troponin I isolated from human heart tissue.

Biomarkers↗
PubMed1995

Immunization with glycoprotein C of equine herpesvirus-1 is associated with accelerated virus clearance in a murine model.

The glycoprotein C (gC) gene of equine herpesvirus-1 (EHV-1) was expressed in insect cells by a recombinant baculovirus as several products with apparent molecular weights of 66 kDa-80 kDa. The baculovirus EHV-1 gC products were recognised by monoclonal antibody and by EHV-1 convalescent equine sera, indicating conservation of antigenic determinants and confirming this glycoprotein as a target for the equine immune system. Mice immunized with recombinant EHV-1 gC showed accelerated clearance of EHV-1 from respiratory tissues following intranasal challenge. Virus clearance was accompanied by virus specific antibodies and by cell mediated immune responses measured by a delayed type hypersensitivity reaction and lymphocyte stimulation by killed EHV-1 as antigen.

Animals↗
PubMed1994

Geographical distribution of haplotypes in Swedish families with Huntington's disease.

This study was planned to determine the number of origins of the mutation underlying Huntington's disease (HD) in Sweden. Haplotypes were constructed for 23 different HD families, using six different polymorphisms [(CCG)n, GT70, 674, BS1, E2 and 4.2], including two within the gene. In addition, extensive genealogical investigations were performed, and the geographical origin of the haplotypes was studied. Ten different haplotypes were observed suggesting multiple origins for the HD mutation in Sweden. Analysis of the two polymorphic markers within the HD gene (the CCG repeat and GT70) indicates that there are at least three origins for the HD mutation in Sweden. One of these haplotypes (7/A) accounts for 89% of the families, suggesting that the majority of the Swedish HD families are related through a single HD mutation of ancient origin. Furthermore, three of the families that were previously considered to be unrelated could be traced to a common ancestor in the 15th century, a finding that is consistent with this hypothesis.

Alleles↗
PubMed1993

Support for founder effect for two lipoprotein lipase (LPL) gene mutations in French Canadians by analysis of GT microsatellites flanking the LPL gene.

Mutations in the human lipoprotein lipase (LPL) gene are one of the major causes of familial chylomicronemia. We have characterized two polymorphic GT microsatellites flanking this gene. Two LPL mutations that are extremely frequent in French Canadians appear to be in complete linkage disequilibrium with specific LPL microsatellite haplotypes indicating a founder effect within this population.

Adult↗
PubMed1992

Bacteriophage P22 portal protein is part of the gauge that regulates packing density of intravirion DNA.

The complex double-stranded DNA bacteriophages assemble DNA-free protein shells (procapsids) that subsequently package DNA. In the case of several double-stranded DNA bacteriophages, including P22, packaging is associated with cutting of DNA from the concatemeric molecule that results from replication. The mature intravirion P22 DNA has both non-unique (circularly permuted) ends and a length that is determined by the procapsid. In all known cases, procapsids consist of an outer coat protein, an interior scaffolding protein that assists in the assembly of the coat protein shell, and a ring of 12 identical portal protein subunits through which the DNA is presumed to enter the procapsid. To investigate the role of the portal protein in cutting permuted DNA from concatemers, we have characterized P22 portal protein mutants. The effects of several single amino acid changes in the P22 portal protein on the length of the DNA packaged, the density to which DNA is condensed within the virion, and the outer radius of the capsid have been determined. The results obtained with one mutant (NT5/1a) indicate no change (+/- 0.5%) in the radius of the capsid, but mature DNA that is 4.7% longer and a packing density that is commensurately higher than those of wild-type P22. Thus, the portal protein is part of the gauge that regulates the length and packaging density of DNA in bacteriophage P22. We argue that these findings make models for DNA packaging less likely in which the packing density is a property solely of the coat protein shell or of the DNA itself.

Base Sequence↗
PubMed1992

Epilepsy: patient perceptions of their condition.

The objective of this study was to ascertain the perceptions of people with epilepsy about their condition. Nine hundred and eight questionnaires were sent to members of epilepsy associations, with a 45% response rate, and 625 questionnaires were sent to neurologists for their patients to complete, with a response rate of 16.5%. The results reinforce and extend previous observations that there is an ongoing need for educating health care professionals and persons with epilepsy about the condition. Matters pertaining to driving, the unpredictability of seizures, lack of employment and cognitive difficulties were of major concern to the respondents. The present data also highlighted the vexed relationship between stress and seizure control, which needs to be further investigated. These data should be of value to doctors and other health care professionals in their dealings with people with epilepsy. It should also provide epilepsy associations with data upon which they might be able to plan education services.

Activities of Daily Living↗
PubMed1991

Single-dose concentrations of tinidazole in gingival crevicular fluid, serum, and gingival tissue in adults with periodontitis.

Previous studies have shown that metronidazole is effective in the treatment of subgingival microflora associated with destructive periodontitis. The aim of this study was to determine whether tinidazole, a close analogue of metronidazole, would reach sufficient concentrations in serum, gingival crevicular fluid, and gingival tissue, to inhibit putative periodontopathic bacteria. Ten adult patients with moderate to advanced periodontitis took a single 2-g dose of tinidazole orally. Samples were assayed by high-performance liquid chromatography. The concentrations of tinidazole in serum and GCF were in a similar range (3.2-46.5 micrograms/mL). Tinidazole was not detected in the GCF in three of the patients. The drug was found in gingival tissue obtained at two h (0.17 +/- 0.14 micrograms/mg) and six h (0.15 +/- 0.18 micrograms/mg) after oral administration. The mean concentration of tinidazole in serum at 24 h (13 +/- 3.0 micrograms/mL) is greater than the minimum inhibitory concentration for anaerobic bacteria as reported by others. The present data suggest that a single 2-g oral dose of tinidazole may lead to the presence of potentially bactericidal levels of tinidazole for up to 24 h in the periodontal pockets of some patients with periodontitis.

Administration, Oral↗
PubMed1991

Linkage disequilibrium and modification of risk for Huntington disease.

The major limitation in performing predictive testing for Huntington disease (HD) is the unavailability of DNA from crucial family members. In our program approximately 20% (36/183) of persons have been excluded from predictive testing because of this reason. The major aim of this study was to examine whether data derived from linkage disequilibrium could modify risk analysis for persons at risk for HD. As a first step, we assessed whether the previously reported linkage disequilibrium between alleles recognized by probe pBS674E-D at locus D4S95 remained significant in a much larger data set. A total of 1,150 chromosomes from 622 individuals--200 affected and 422 unaffected--from 118 families were assessed. Significant haplotype association was detected with AccI and MboI RFLPs at the locus D4S95, with all the families (P = .00003), as well as for a subset from the United Kingdom (P = .0037). Data derived from linkage disequilibrium studies using D4S95 modifies the risk for HD, especially in persons of U.K. descent. Utilization of this approach for risk modification of HD awaits both validation of these data and additional information concerning ethnic-specific alleles at the D4S95 locus.

Adult↗
PubMed1990

Regional cerebral glucose metabolism in Turner syndrome.

Regional cerebral glucose metabolism was examined in females with Turner syndrome, a sex chromosome abnormality. Previous studies have found a visual/spatial cognitive anomaly in these women but, to date, no abnormalities in brain structure or function have been associated with the condition. In the present study, decreases in regional metabolism were found in the occipital and parietal cortex. The involvement of the occipital cortex, although consistent with the observed cognitive anomalies, has not been suggested previously as an area dysfunction. Because the occipital cortex is a primary sensory cortex, the reduction of glucose metabolism in the parietal cortex may reflect a lack of innervation from the occipital cortex. Besides insight into the functional specialization of the brain, these findings are also consistent with previous reports on animals regarding the effects of estrogen in brain maturation.

Adult↗
PubMed1990

Ethical and legal dilemmas arising during predictive testing for adult-onset disease: the experience of Huntington disease.

The goal of predictive testing is to modify the risk for currently healthy individuals to develop a genetic disease in the future. Such testing using polymorphic DNA markers has had major application in Huntington disease. The Canadian Collaborative Study of Predictive Testing for Huntington Disease has been guided by major principles of medical ethics, including autonomy, beneficence, confidentiality, and justice. Numerous ethical and legal dilemmas have arisen in this program, challenging these principles and occasionally casting them into conflict. The present report describes these dilemmas and offers our approach to resolving them. These issues will have relevance to predictive-testing programs for other adult-onset disorders.

Abortion, Eugenic↗
PubMed1989

A deletion map of the WAGR region on chromosome 11.

The WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) region has been assigned to chromosome 11p13 on the basis of overlapping constitutional deletions found in affected individuals. We have utilized 31 DNA probes which map to the WAGR deletion region, together with six reference loci and 13 WAGR-related deletions, to subdivide this area into 16 intervals. Specific intervals have been correlated with phenotypic features, leading to the identification of individual subregions for the aniridia and Wilms tumor loci. Delineation, by specific probes, of multiple intervals above and below the critical region and of five intervals within the overlap area provides a framework map for molecular characterization of WAGR gene loci and of deletion boundary regions.

Abnormalities, Multiple↗
PubMed1988

Sequence and expression of Tangier apoA-I gene.

We have isolated and characterized the apoA-I gene from a lambda L47.1 genomic library constructed with DNA obtained from the lymphocytes of a Tangier disease patient. The DNA-derived protein sequence of Tangier apoA-I was found to be identical to normal apoA-I. Transfection of mouse C127 cells with a recombinant vector containing the Tangier apoA-I gene (pSV2-gpt apoA-I) allowed selection of stable clones resistant to aminopterin and mycophenolic acid. Analysis of these clones for apoA-I synthesis showed that the protein secreted by cells expressing the Tangier apoA-I gene was indistinguishable from the apoA-I secreted by HepG2 cells. These experiments establish that the Tangier apoA-I gene is structurally normal. It appears that the molecular basis of Tangier disease is not related to apoA-I structure or regulation of expression, but rather to other factors pertinent to apoA-I and high-density lipoprotein metabolism.

Amino Acid Sequence↗
PubMed1988

Analysis in vivo of the bacteriophage P22 headful nuclease.

Bacteriophage P22 packages its double-stranded DNA chromosomes from concatemeric replicating DNA in a processive, sequential fashion. According to this model, during the initial packaging event in such a series the packaging apparatus recognizes a nucleotide sequence, called pac, on the DNA, and then condenses DNA within the coat protein shell unidirectionally (rightward) from that point. DNA ends are generated near the pac site before or during the condensation reaction. The right end of the mature chromosome is created by a cut made in the DNA by the "headful nuclease" after a complete chromosome is condensed within the phage head. Subsequent packaging events on that concatemeric DNA begin at the end generated by the headful cut of the previous event and proceed in the same direction as the previous event. We report here accurate measurements of the P22 chromosome length (43,400( +/- 750) base-pairs, where the uncertainty is the range in observed lengths), genome length (41,830( +/- 315) base-pairs, where the uncertainty represents the accuracy with which the length is known), the terminal redundancy (1600( +/- 750) base-pairs or 3.8( +/- 1.8)%, where the uncertainty is the observed range) and the imprecision in the headful measuring device ( +/- 750 base-pairs or +/- 1.7%). In addition, we present evidence for a weak nucleotide sequence specificity in the headful nuclease. These findings lend further support to, and extend our understanding of, the sequential series model of P22 DNA packaging.

DNA, Viral↗
PubMed1988

Prenatal diagnosis of asplenia/polysplenia syndrome.

Complex congenital heart disease with atrioventricular block was detected prenatally in two fetuses at 34 and 28 weeks' gestation. The spleen was not seen on ultrasonographic examination in either fetus, suggesting polysplenia/asplenia syndrome. Both infants died shortly after delivery and the autopsies confirmed this diagnosis. Recommendations for sonographic screening of the fetal spleen in cases of prenatal detection of complex heart disease or cardiac dysrhythmia are discussed.

Abnormalities, Multiple↗
PubMed1988

Comparison of gemfibrozil and clofibrate on serum lipids in familial combined hyperlipidemia. A randomized placebo-controlled, double-blind, crossover clinical trial.

A randomized double blind, placebo-controlled crossover design was used to determine the efficacy of gemfibrozil and clofibrate in the treatment of familial combined hyperlipidemia and to determine which one of these agents would be more effective. Sixteen patients, 12 men and 4 women, mean age 49.5 years (40-68 yrs), had the entry criteria of increased cholesterol and/or triglyceride with an increase in triglyceride and/or cholesterol in one or more first degree relatives and/or family history of premature cardiovascular disease. Patients received 6 weeks of placebo followed by clofibrate 1000 mg bid or gemfibrozil 600 mg bid for 12 weeks, placebo for 6 weeks and the other drug for 12 weeks. Plasma total cholesterol, triglycerides, HDL-C, LDL-C, apo B and apo A-I were measured every 6 weeks during the study. Gemfibrozil was associated with a significant (P less than 0.05) decrease in plasma triglyceride concentration compared to placebo but it was not significantly different compared to clofibrate. For ease of comparison, the mean value for serum triglycerides during gemfibrozil treatment (average of the 6 and 12 week measurements) was calculated and was 232 +/- 198 mg/dl (mean +/- 1 SD) compared to the average of the placebo treatment values of 381 +/- 410 mg/dl and the average value during the clofibrate treatment period of 217 +/- 178 mg/dl. HDL-C was significantly (P less than 0.05) increased with both drugs and to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Initiation of bacteriophage P22 DNA packaging series. Analysis of a mutant that alters the DNA target specificity of the packaging apparatus.

Bacteriophage P22 is thought to package its double-stranded DNA chromosome from concatemeric replicating DNA in a "processive" sequential fashion. According to this model, during the initial packaging event in such a series the packaging apparatus recognizes a nucleotide sequence, called pac, on the DNA, and then condenses DNA within the coat protein shell unidirectionally from that point. DNA ends are generated near the pac site before or during the condensation reaction. The opposite end of the mature chromosome is created by a cut made in the DNA after a complete chromosome is condensed within the phage head. Subsequent packaging events on that concatemeric DNA begin at the end generated by the headful cut of the previous event and proceed in the same direction as the previous event. We report here the identification of a consensus nucleotide sequence for the pac site, and present evidence that supports the idea that the gene 3 protein is a central participant in this recognition event. In addition, we tentatively locate the portion of the gene 3 protein that contacts the pac site during the initiation of packaging.

Base Sequence↗
PubMed1987

Controlling for cerebral atrophy in positron emission tomography data.

This article outlines a simple method for estimating the degree of cerebral atrophy and subsequent experimental control for the effects of cerebral atrophy on regional metabolic values measured with positron emission tomography. It is suggested that rather than correcting derived values for atrophy, less potential error is introduced by experimentally controlling for regional atrophy when possible. By treating the derived metabolic rates and the measure of atrophy as two separate variables, it is also possible to establish whether there actually is a demonstrable relationship between the two measures.

Adolescent↗