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Biomedical subjects

M J Mitchell

Publications and source records attributed to M J Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed2000

Different neuromuscular recruitment patterns during eccentric, concentric and isometric contractions.

Aim. The purpose of this study was to determine the neuromuscular fatigue profiles during 100 s isometric (ISO), concentric (CON), and eccentric (ECC) activity.Methods. Twelve subjects (age 25.1+/-3.7 years, mass 70.1+/-8.2 kg, mean+/-SD) performed ISO, CON and ECC maximal voluntary contractions and 100 s endurance trials on an isokinetic dynamometer. Raw EMG data were recorded throughout each trial from the rectus femoris of the right limb. Corresponding data for integrated electromyography (IEMG), percentile frequency shifts (MPFS) and peak torque output were divided into five 5 s epochs and subsequently normalised with the first epoch being the reference point, in order to assess changes over time.Results. There were no significant differences between ECC, CON and ISO peak torque output (211+/-63 vs 169+/-41 vs 177+/-61 Nm; ECC, CON, ISO) and IEMG activity (280+/-143 vs 305+/-146 vs 287+/-143 mV; ECC, CON, ISO) during maximal contractions. Serial reductions in torque output were greatest in ISO in which torque output during the final epoch was 31+/-13% of initial values, similar to the final torque values in CON (58+/-15%), but significantly less than ECC (108.6+/-38.6%; P<0. 001) values. In CON and ECC, IEMG was maintained (95+/-27% and 93+/-21%; CON and ECC), whereas IEMG for ISO decreased to 38+/-13% of initial values. The greatest reduction in MPFS occurred in CON (69+/-10%) compared to ISO (78+/-9%; P<0.05) and ECC (93+/-6%; P<0.001).Conclusion. These data demonstrate distinct neuromuscular fatigue profiles for the different types of muscle contraction. Whereas eccentric activity was largely fatigue resistant, isometric and concentric contractions displayed different neuromuscular fatigue profiles.

Adult↗
PubMed2000

Dendritic cells permit identification of genes encoding MHC class II-restricted epitopes of transplantation antigens.

Minor or histocompatibility (H) antigens are recognized by CD4+ and CD8+ T lymphocytes as short polymorphic peptides associated with MHC molecules. They are the targets of graft versus host and graft versus leukemia responses following bone marrow transplantation between HLA-identical siblings. Several genes encoding class I-restricted minor H epitopes have been identified, but approaches used for these have proved difficult to adapt for cloning class II-restricted minor H genes. We have combined the unique antigen-presenting properties of dendritic cells and high levels of episomal expression following transfection of COS cells to identify a Y chromosome gene encoding two HY peptide epitopes, HYAb and HYEk.

Amino Acid Sequence↗
PubMed2000

Use of the site percutaneous breast biopsy device.

A new technique is described for image guided percutaneous diagnostic excision biopsy of non-palpable mammographically detected breast lesions. This method involves insertion of a localizing guide wire under stereotactic guidance followed by insertion of the 15 mm diameter biopsy device which is positioned within the breast immediately proximal to the target lesion. A cylindrical cannula is advanced over the lesion which is then separated from the surrounding breast tissue by deploying a garrote wire at the distal end of the cannula. The biopsy device is then removed with the target lesion contained within the cannula. The mammographic lesion is excised without removing any excess adjacent breast tissue, and in one piece, so allowing histological examination of the whole lesion. The experience of the first three cases is described with imaging and histological correlation.

Journal Article↗
PubMed2000

The human Y chromosome genes BPY2, CDY1 and DAZ are not essential for sustained fertility.

Deletions of the AZFc interval of the human Y chromosome are found in >5% of male patients with idiopathic infertility and are associated with a severely reduced sperm count. The most common deletion type is large (>1 Mb) and removes members of the Y-borne testis-specific gene families of BPY2, CDY1, DAZ, PRY, RBMY2 and TTY2, which are candidate AZF genes. Four exceptional individuals who have transmitted a large AZFc deletion naturally to their infertile sons have, however, been described. In three cases, transmission was to an only son, but in the fourth case a Y chromosome, shown to be deleted for all copies of DAZ, was transmitted from a father to his four infertile sons. Here we present a second family of this latter type and demonstrate that an AZFc-deleted Y chromosome lacking not only DAZ, but also BPY2 and CDY1, has been transmitted from a father to his three infertile sons. Polymerase chain reaction (PCR) and Southern blot analyses revealed no difference in the size of the AZFc deletion in the father and his sons. We propose that the father carries rare alleles of autosomal or X-linked loci which suppress the infertility that is frequently associated with the absence of AZFc.

Adult↗
PubMed1999

Automated detection of the factor V Leiden mutation using the LCx microparticle enzyme immunoassay.

The factor V Leiden mutation, a G-->A transition at position 1691 in exon 10 of the gene that codes for factor V, produces an Arg506Gln substitution and is the most common genetic risk factor for venous thrombosis. We have developed a rapid, sensitive, and specific method to detect the factor V Leiden mutation in genomic DNA from whole blood by PCR amplification and microparticle enzyme immunoassay detection using the Abbott LCx instrument. We compared this automated method with the standard procedure using restriction endonuclease digestion of PCR products followed by gel electrophoresis in blinded experiments. In 130 patients (from Veterans Affairs medical centers) with deep venous thromboses, including 24 heterozygotes with the factor V Leiden mutation, there was complete agreement between the two methods. The assay was also able to distinguish heterozygotes from homozygotes. This method, which carries a low potential for cross-contamination of samples, should be a useful routine test for the factor V Leiden mutation in clinical laboratories with sufficient demand for molecular diagnostic assays using the LCx instrument.

Autoanalysis↗
PubMed1999

Immune tolerance therapy for haemophilia A patients with acquired factor VIII alloantibodies: comprehensive analysis of experience at a single institution.

Immune Tolerance Therapy for Haemophilia A Patients with Acquired Factor VIII Alloantibodies: Comprehensive Analysis of Experience at a Single Institution Eleven children with severe haemophilia A associated with the IVS 22 inversion and acquired high titre neutralising antibodies to factor VIII underwent immune tolerance induction. HLA class I and high resolution class II type is detailed for each patient. A three phase approach to immune tolerance induction was used. During phase 1, which lasted a median of six weeks, patients received factor VIII 100 IU/kg twice daily. Phase 2 comprised a factor VIII dose reduction to 100 IU/kg once daily, and continued for a median duration of 14 weeks. Subsequently 10 of the 11 patients satisfied the criteria of absent factor VIII neutralising activity by the Bethesda method, and a factor VIII elimination half life of greater than 5 h, allowing progression to phase 3, a further factor VIII dose reduction to 50 IU/kg three times weekly. A model for dose reduction as factor VIII tolerance evolves, based on pharmacokinetic analysis, is described.

Child, Preschool↗
PubMed1998

The mouse Y chromosome interval necessary for spermatogonial proliferation is gene dense with syntenic homology to the human AZFa region.

The Delta Sxrb deletion interval of the mouse Y chromosome contains Spy, a spermatogenesis factor gene(s) whose expression is essential for the postnatal development of the mitotic germ cells, spermatogonia. The boundaries of Delta Sxrb are defined by the duplicated genes Zfy1 and Zfy2 and four further genes have previously been mapped within the interval: Ube1y and Smcy, linked with Zfy1 on a contig of 250 kb, and Dffry and Uty, which were unanchored. The interval was estimated to be >450 kb. In order to identify any further gene(s) that may underlie Spy, systematic exon trapping was performed on an extended contig, anchored on Zfy1, which covers 750 kb of the Delta Sxrb interval. Exons from two novel genes were isolated and placed together with Dffry and Uty on the contig in the order Dffry-Dby-Uty-Tspy-Eif2gammay-Smcy- Ube1y-Zfy1. All the genes, with the double exception of Tspy, are X-Y homologous and produce putatively functional, spliced transcripts. The tight linkage and order of Dffry, Dby and Uty was shown to be conserved in deletion intervals 5C/5D of the human Y chromosome by the construction of a contig of human PAC and YAC clones; this represents the first example of syntenic homology between Y chromosomes from two distinct mammalian orders. Interval 5C/5D contains the distal boundary of the AZFa interval, which, like Delta Sxrb, is believed to be necessary for spermatogonial development in the prepubertal testis. Our results therefore show that AZFa and Spy may be encoded by homologous genes.

Animals↗
PubMed1998

Characterization of genes encoding translation initiation factor eIF-2gamma in mouse and human: sex chromosome localization, escape from X-inactivation and evolution.

The Delta Sxrb interval of the mouse Y chromosome is critical for spermatogenesis and expression of the male-specific minor transplantation antigen H-Y. Several genes have been mapped to this interval and each has a homologue on the X chromosome. Four, Zfy1 , Zfy2 , Ube1y and Dffry , are expressed specifically in the testis and their X homologues are not transcribed from the inactive X chromosome. A further two, Smcy and Uty , are ubiquitously expressed and their X homologues escape X-inactivation. Here we report the identification of another gene from this region of the mouse Y chromosome. It encodes the highly conserved eukaryotic translation initiation factor eIF-2gamma. In the mouse this gene is ubiquitously expressed, has an X chromosome homologue which maps close to Dmd and escapes X-inactivation. The coding regions of the X and Y genes show 86% nucleotide identity and encode putative products with 98% amino acid identity. In humans, the eIF-2gamma structural gene is located on the X chromosome at Xp21 and this also escapes X-inactivation. However, there is no evidence of a Y copy of this gene in humans. We have identified autosomal retroposons of eIF-2gamma in both humans and mice and an additional retroposon on the X chromosome in some mouse strains. Ark blot analysis of eutherian and metatherian genomic DNA indicates that X-Y homologues are present in all species tested except simian primates and kangaroo and that retroposons are common to a wide range of mammals. These results shed light on the evolution of X-Y homologous genes.

Amino Acid Sequence↗
PubMed1998

The origin and loss of the ubiquitin activating enzyme gene on the mammalian Y chromosome.

Mammalian sex chromosomes are thought to be descended from a homologous pair of autosomes: a testis-determining allele which defined the Y chromosome arose, recombination between the nascent X and Y chromosomes became restricted and the Y chromosome gradually lost its non-essential genetic functions. This model was originally inferred from the occurrence of few Y-linked genetic traits, pairing of the X and Y chromosomes during male meiosis and, more recently, the existence of X-Y homologous genes. The comparative analysis of such genes is a means by which the validity of this model can be evaluated. One well-studied example of an X-Y homologous gene is the ubiquitin activating enzyme gene ( UBE1 ), which is X-linked with a distinct Y-linked gene in many eutherian ('placental') and metatherian (marsupial) mammals. Nonetheless, no UBE1 homologue has yet been detected on the human Y chromosome. Here we describe a more extensive study of UBE1 homologues in primates and a prototherian mammal, the platypus. Our findings indicate that UBE1 lies within the X-Y pairing segment of the platypus but is absent from the human Y chromosome, having been lost from the Y chromosome during evolution of the primate lineage. Thus UBE1 illustrates the key steps of 'autosomal to X-specific' evolution of genes on the sex chromosomes.

Animals↗
PubMed1998

Rodent Y chromosome TSPY gene is functional in rat and non-functional in mouse.

Recombination is believed to prevent genetic deterioration in sexual populations because it allows conservation of functional genotypes by removing deleterious mutations. Moreover, evidence that non-recombining segments of a genome deteriorate is provided by genetic experiments in Drosophila and yeast. Y chromosomes generally do not recombine along most of their length, and thus Y chromosome genes, despite having been selectively maintained for their function, could be lost from the genome. Here we present definitive evidence that functional Y genes can be lost from the mammalian genome. TSPY genes must have been selectively maintained on the mammalian Y chromosome since before the radiation of eutheria, 80 million years ago, as they are found conserved on the Y chromosome in two mammalian orders: primate and artiodactyl. We have now identified TSPY on the rodent Y chromosome, in mouse and rat. The gene structure and expression of rat TSPY suggest that it is a functional, testis-specific gene, but the closely related mouse gene, Tspy, has clearly become non-functional, producing only low levels of aberrantly spliced transcripts. Thus TSPY lost its function in the mouse lineage after its divergence from the rat lineage. So, in the case of Tspy at least, the absence of recombination does appear to have led to the loss of a functional gene.

Animals↗
PubMed1997

Effects of the neem tree compounds azadirachtin, salannin, nimbin, and 6-desacetylnimbin on ecdysone 20-monooxygenase activity.

The effects of azadirachtin, salannin, nimbin, and 6-desacetylnimbin on ecdysone 20-monooxygenase (E-20-M) activity were examined in three insect species. Homogenates of wandering stage third instar larvae of Drosophila melanogaster, or abdomens from adult female Aedes aegypti, or fat body or midgut from fifth instar larvae of Manduca sexta were incubated with radiolabeled ecdysone and increasing concentrations (from 1 x 10(-8) to 1 x 10(-3) M) of the four compounds isolated from seed kernels of the neem tree, Azadirachta indica. All four neem tree compounds were found to inhibit, in a dose-dependent fashion, the E-20-M activity in three insect species. The concentration of these compounds required to elicit a 50% inhibition of this steroid hydroxylase activity in the three insect species examined ranged from approximately 2 x 10(-5) to 1 x 10(-3).

Aedes↗
PubMed1997

Hip fracture surgery in Nova Scotia: a comparison of treatment provided by "generalist" general surgeons and orthopedic surgeons.

OBJECTIVE: To determine quality of hip fracture services provided by "generalist" general surgeons (generalists) in Nova Scotia. DESIGN: Chart review and postoperative, blinded, random-ordered radiologic analysis. SETTING: Three community hospitals and 1 tertiary care hospital in Nova Scotia. PARTICIPANTS: Seven generalists who performed 120 hip fracture repairs and 7 orthopedic surgeons (specialists) who performed 135 hip fracture repairs. OUTCOME MEASURES: Patient demographics, preoperative, perioperative, postoperative and discharge information, technical quality of reduction as determined through postoperative radiologic assessment. RESULTS: There were no differences between patients treated by generalists and those treated by specialists with respect to age, sex, American Society of Anesthesiologists' class, level of function and fracture type. Intraoperatively, the patient groups were similar with respect to type of anesthesia, use of antibiotics, number of transfusions and surgical complications. Significant differences were noted in length of operation (54.4 v. 41.1 minutes), use of C-arm imaging (6.7% v. 85.9%) and management of Garden classes 1 and 2 subcapital fractures. Postoperatively, the 2 groups had similar numbers of medical complications, wound complications, reoperations, readmissions and deaths, and a similar level of function on discharge. Significant differences included the number of intensive care unit admissions (5.8% v. 15.6%) and length of stay there (5.7 v. 2.8 days) and of postoperative stay (14.5 v. 10.7 days). The assessment of radiographs did not demonstrate any significant difference in the quality of reduction. CONCLUSION: In Nova Scotia the outcomes of hip fracture surgery performed by generalists are comparable to those performed by specialists.

Activities of Daily Living↗