Search PubMed⌕ Search

Biomedical subjects

M J Mitchell

Publications and source records attributed to M J Mitchell.

At least 19 recordsLinked to original sources
PubMed2005

Influence of ageing of residues on the availability of herbicides for leaching.

Losses by leaching of chlorotoluron, isoproturon and triasulfuron from small intact columns of a structured clay loam and an unstructured sandy loam soil were measured in five separate field experiments. In general, losses of all three herbicides were greater from the clay loam than from the sandy loam soil and the order between herbicides was always triasulfuron >> isoproturon > chlorotoluron. Differences between experiments were also consistent for every soil/herbicide combination. There was no relationship between total loss and either total rainfall or cumulative leachate volume. When weighting factors were applied to the rainfall data to make early rainfall more important than later rainfall, there were significant positive relationships between cumulative weighted rainfall and total losses. Also, there were significant negative correlations between total losses and the delay to accumulation of 25 mm rainfall (equivalent to one pore volume of available water) in the different experiments. In laboratory incubations, there was a more rapid decline in aqueous (0.01 M calcium chloride) extractable residues than in total solvent extractable residues indicating increasing sorption with residence time. However, the rate of change in water extractable residues could not completely explain the decrease in leachability with ageing of residues in the field. Short-term sorption studies with aggregates of the two soils indicated slower sorption by those of the clay loam than by those of the sandy loam suggesting that diffusion into and out of aggregates may affect availability for leaching in the more structured soil. Small scale leaching studies with aggregates of the soils also demonstrated reductions in availability for leaching as residence time in soil was increased, which could not be explained by degradation. These results therefore indicate that time-dependent sorption processes are important in controlling pesticide movement in soils, although the data do not give a mechanistic explanation of the changes in leaching with ageing of residues.

Adsorption↗
PubMed2004

Sequence family variant loss from the AZFc interval of the human Y chromosome, but not gene copy loss, is strongly associated with male infertility.

BACKGROUND: Complete deletion of the complete AZFc interval of the Y chromosome is the most common known genetic cause of human male infertility. Two partial AZFc deletions (gr/gr and b1/b3) that remove some copies of all AZFc genes have recently been identified in infertile and fertile populations, and an association study indicates that the resulting gene dose reduction represents a risk factor for spermatogenic failure. METHODS: To determine the incidence of various partial AZFc deletions and their effect on fertility, we combined quantitative and qualitative analyses of the AZFc interval at the DAZ and CDY1 loci in 300 infertile men and 399 control men. RESULTS: We detected 34 partial AZFc deletions (32 gr/gr deletions), arising from at least 19 independent deletion events, and found gr/gr deletion in 6% of infertile and 3.5% of control men (p>0.05). Our data provide evidence for two large AZFc inversion polymorphisms, and for relative hot and cold spots of unequal crossing over within the blocks of homology that mediate gr/gr deletion. Using SFVs (sequence family variants), we discriminate DAZ1/2, DAZ3/4, CDY1a (proximal), and CDY1b (distal) and define four types of DAZ-CDY1 gr/gr deletion. CONCLUSIONS: The only deletion type to show an association with infertility was DAZ3/4-CDY1a (p = 0.042), suggesting that most gr/gr deletions are neutral variants. We see a stronger association, however, between loss of the CDY1a SFV and infertility (p = 0.002). Thus, loss of this SFV through deletion or gene conversion could be a major risk factor for male infertility.

Base Sequence↗
PubMed2002

The identification and classification of 41 novel mutations in the factor VIII gene (F8C).

Hemophilia A is a bleeding disorder caused by a quantitative or qualitative deficiency in the coagulation factor VIII. Causative mutations are heterogeneous in nature and are distributed throughout the FVIII gene. With the exception of mutations that result in prematurely truncated protein, it has proved difficult to correlate mutation type/amino acid substitution with severity of disease. We have identified 81 mutations in 96 unrelated patients, all of whom have typed negative for the common IVS-22 inversion mutation. Forty-one of these mutations are not recorded on F8C gene mutation databases. We have analyzed these 41 mutations with regard to location, whether or not each is a cross-species conserved region, and type of substitution and correlated this information with the clinical severity of the disease. Our findings support the view that the phenotypic result of a mutation in the FVIII gene correlates more with the position of the amino acid change within the 3D structure of the protein than with the actual nature of the alteration.

Animals↗
PubMed2001

Expression and conservation of processed copies of the RBMX gene.

RBMX and RBMY are members of an ancient pair of genes located on the sex chromosomes that encode RNA-binding proteins involved in splicing. These genes have differentiated and evolved separately on the X and Y Chromosomes. RBMY has acquired a testis-specific function, whereas, as shown here, RBMX is ubiquitously expressed and is subject to X inactivation. We have also found that multiple processed copies of RBMX are present in the human genome. RBMX-like sequences (RBMXLs) located on human Chrs 1, 4, 6, 9 (9p13 and 9p24), 11, 20, and X lack introns and thus probably result from retroposition events. We found RBMXLs to be conserved in primates and great apes at corresponding chromosomal locations, indicating that they arose prior to the divergence of human. Some of the RBMXLs show insertions, deletions, and stop codons, which would probably result in nonfunctional proteins. The RBMXL on Chr 20 is deleted in some individuals. Two of the largely intact RBMXLs, located on Chrs 1 and 9p13, are expressed in different tissues and may encode novel proteins involved in splicing in a tissue-specific manner. The RBMXL located at 9p13 is specifically expressed in testis, and to a lesser extent in brain, and may therefore play a role in testis function. This autosomal, testis-specific copy of RBMX could potentially compensate for RBMX that is presumably inactivated in male germ cells, in a manner analogous to autosomal retroposed copies of other X-linked genes.

Amino Acid Sequence↗
PubMed2001

A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis.

In mouse and man, deletions of specific regions of the Y chromosome have been linked to early failure of spermatogenesis and consequent sterility; the Y chromosomal gene(s) with this essential early role in spermatogenesis have not been identified. The partial deletion of the mouse Y short arm (the Sxrb deletion) that occurred when Tp(Y)1CtSxr-b (hereafter Sxrb) arose from Tp(Y)1CTSxr-b (hereafter Sxra) defines Spy, a Y chromosomal factor essential for normal spermatogonial proliferation. Molecular analysis has identified six genes that lie within the deletion: Ube1y1 (refs. 4,5), Smcy, Uty, Usp9y (also known as Dffry), Eif2s3y (also known as Eif-2gammay) and Dby10; all have closely similar X-encoded homologs. Of the Y-encoded genes, Ube1y1 and Dby have been considered strong candidates for mouse Spy function, whereas Smcy has been effectively ruled out as a candidate. There is no Ube1y1 homolog in man, and DBY, either alone or in conjunction with USP9Y, is the favored candidate for an early spermatogenic role. Here we show that introduction of Ube1y1 and Dby as transgenes into Sxrb-deletion mice fails to overcome the spermatogenic block. However, the introduction of Eif2s3y restores normal spermatogonial proliferation and progression through meiotic prophase. Therefore, Eif2s3y, which encodes a subunit of the eukaryotic translation initiation factor Eif2, is Spy.

Animals↗
PubMed2001

Multidimensional assessment of pain in pediatric sickle cell disease.

OBJECTIVE: To conduct a multidimensional assessment of pain in children with sickle cell disease (SCD). Variables included parent and child reports of pain location and intensity, qualitative descriptors of pain, perceptions regarding the seriousness and severity of SCD, and environmental and emotional factors associated with pain. METHODS: We replicated previous SCD pain research and applied advanced assessment methodology and research design to a population of pediatric SCD patients and their caregivers. RESULTS: Convergence of data supports the utility of multidimensional pain assessment with parents and children with SCD. SCD pain is experienced as intense and severe in home and hospital environments. CONCLUSIONS: Findings support including children as reporters in clinical assessment of SCD pain. Integration of assessment strategies into home-based pain management may improve health outcomes. Future research should target biobehavioral treatment for pediatric SCD pain.

Anemia, Sickle Cell↗
PubMed2001

Observational assessment of family functioning at mealtime in preschool children with cystic fibrosis.

OBJECTIVE: To examine functioning during a dinner meal in families of a child with a chronic illness that requires dietary treatment recommendations, as compared to families of a child without a chronic illness. METHODS: Ratings of seven dimensions of family functioning on the McMaster Mealtime Family Interaction Coding System (MICS) were obtained on 29 families of children with CF and 29 families of children with no chronic illness, ages 2 to 6 years, during a videotaped dinner meal at home. RESULTS: Ratings of families with a child with CF were significantly lower than those for families of children without a chronic illness on Overall Family Functioning and five of the six MICS dimensions: Communication, Interpersonal Involvement, Affect Management, Behavior Control, and Role Allocation and approached significance on the Task Accomplishment dimension. The ratings of families of a child with CF were in the "clinically significant" range on all subcales, including Task ACCOMPLISHMENT. CONCLUSIONS: This study suggests that family functioning at mealtimes may be different in families of children with CF in which explicit dietary guidelines exist than in families of children with no illness or dietary guidelines. These results are discussed in terms of global family functioning and treatment approaches to dietary treatment recommendations.

Child, Preschool↗
PubMed2001

A rapid and cost-effective method for analysis of three common genetic risk factors for thrombosis.

A simple, rapid and cost-effective method for the analysis of three of the most widely screened genetic risk factors for thrombosis has been established. The protocol developed uses blood spots stored on filter paper (Guthrie spots) as well as DNA extracted from anticoagulated blood. The use of Guthrie spots taken at birth enables the retrospective study of patients who develop thrombotic complications without necessitating resampling. Following isolation of DNA, conventional fluorescence-labelled polymerase chain reaction (PCR) is performed using a thermostable DNA polymerase. Denatured, single-stranded PCR products are analysed on a semi-automated capillary-based genetic analyser, the data being stored electronically. This sensitive protocol obviates the need for endonuclease digestion and the associated gel running and documentation, and leads to a reduction in the recurrent costs of laboratory consumables.

Blood Specimen Collection↗
PubMed2001

Magnetic resonance analysis of postsurgical temporal lobectomy.

BACKGROUND AND PURPOSE: The effect of temporal lobe transection area, volume of postoperative gliosis, and surgical technique on patients' seizure-free outcome is unknown. The authors studied the effects of these variables on patients' seizure-free outcome. METHODS: A retrospective review of magnetic resonance imaging examinations acquired 3 to 18 months after temporal lobe resection was carried out for 18 patients with intractable temporal lobe seizures and known postsurgical outcomes for more than 2 years. The total volume of radiologically probable gliosis evident on axial proton-density-weighted images was calculated for each patient using software on an independent console. The total area of temporal lobe surface transected by the scalpel was calculated as well, using sagittal T1-weighted images. The total volume of gliosis, the total area of transected temporal lobe, and the specific type of surgery (sparing vs no sparing of the superior temporal gyrus) were then correlated with the postsurgical outcome of the patients. An examiner with no prior knowledge of the patients' postsurgical outcomes carried out the above calculations and measurements. The patients' postoperative outcome was defined using Engel classifications, and patients were divided into 2 groups: group A with Engel class 1 (n = 9) and group B with Engel classes 2-4 (n = 9). RESULTS: The mean volumes of postoperative gliosis were not significantly different between group A (3592.3 mm3) and group B (4270 mm3). The mean area of transected temporal lobe was also similar between group A (1865.2 mm2) and group B (1930 mm2). With regard to surgical technique, there were 5 patients who had the superior temporal gyrus resected and 13 who did not. Eighty percent of patients with the superior temporal gyrus resected were Engel class 1 or 2, whereas only 20% were of Engel class 3 or 4. CONCLUSIONS: The authors found no clear association between postoperative outcome and residual temporal lobe gliosis, the surgical technique, or the total area of temporal lobe transected by the scalpel.

Adult↗
PubMed2001

Efficacy of calcium sulfate plus decompression bone in lumbar and lumbosacral spinal fusion: preliminary results in 40 patients.

OBJECTIVE: To compare the efficacy of calcium sulfate pellets plus bone obtained from decompression with fresh autologous iliac crest bone in lumbar and lumbosacral spinal fusion with decompression. DESIGN: A prospective randomized clinical trial. SETTING: Four tertiary care centres in Halifax, NS. PATIENTS: All were consenting, skeletally mature and suffering from degenerative disc disease or spondylolisthesis. The first 40 patients from a single test centre are reported; 32 of these had completed 1-year follow-up. INTERVENTIONS: Posterolateral lumbar or lumbosacral spinal fusion with spinal canal decompression and randomized placement of test material (decompression bone plus an equal volume of calcium sulfate pellets) on one side and control material (autologous posterior iliac crest bone of equal volume to the test material) on the contralateral side, which allowed subjects to act as their own control. OUTCOME MEASURES: Assessment of bone formation by radiographic evaluation at 6 and 12 months after fusion by an independent musculoskeletal radiologist blinded to the placement of test material. RESULTS: At 6 and 12 months after fusion, 78% and 88% of patients, respectively, showed bone formation at the test site that was 75% to 100% of, equal to or more than that at the control site. Increases in bone formation at 6 and 12 months were almost identical at both sites. Smoking status, patient gender or age, instrumentation used and volume of graft used were not predictive of outcome. CONCLUSIONS: Calcium sulfate pellets plus decompression bone provided bone formation equivalent to autologous iliac crest bone in a majority of patients. Calcium sulfate pellets plus decompression bone may provide a viable alternative to autologous iliac crest as a graft material for spinal fusion.

Adult↗
PubMed2000

Bivalency and epitope specificity of a high-affinity IgG3 monoclonal antibody to the Streptococcus group A carbohydrate antigen. Molecular modeling of a Fv fragment.

The binding of Strep 9, a mouse monoclonal antibody (mAb) of the IgG3 subclass directed against the cell-wall polysaccharide of Group A Streptococcus (GAS), has been characterized. The intact antibody and proteolytic fragments of Strep 9 bind differently to GAS: the intact mAb and F(ab)2' have greater affinity for the carbohydrate epitope than the monomeric Fab or F(ab)'. A mode of binding in which Strep 9 binds bivalently to portions of the polysaccharide on adjacent chains on GAS is proposed. A competitive ELISA protocol using a panel of carbohydrate inhibitors shows that the branched trisaccharide, beta-D-GlcpNAc-(1-->3)-[alpha-L-Rhap-(1-->2)]-alpha-L-Rhap, and an extended surface are key components of the epitope recognized by Strep 9. Microcalorimetry measurements with the mAb and two synthetic haptens, a tetrasaccharide and a hexasaccharide, show enthalpy-entropy compensation as seen in other oligosaccharide-protein interactions. Molecular modeling of the antibody variable region by homology modeling techniques indicates a groove-shaped combining site that can readily accommodate extended surfaces. Visual docking of an oligosaccharide corresponding to the cell-wall polysaccharide into the site provides a putative model for the complex, in which a heptasaccharide unit occupies the site and the GlcpNAc residues of two adjacent branched trisaccharide units occupy binding pockets within the groove-shaped binding site.

Amino Acid Sequence↗
PubMed2000

The role of human and mouse Y chromosome genes in male infertility.

It was suggested by Ronald Fisher in 1931 that genes involved in benefit to the male (including spermatogenesis genes) would accumulate on the Y chromosome. The analysis of mouse Y chromosome deletions and the discovery of microdeletions of the human Y chromosome associated with diverse defective spermatogenic phenotypes has revealed the presence of intervals containing one or more genes controlling male germ cell differentiation. These intervals have been mapped, cloned and examined in detail for functional genes. This review discusses the genes mapping to critical spermatogenesis intervals and the evidence indicating which are the most likely candidates underlying Y-linked male infertility.

Animals↗
PubMed2000

High dose angiotensin-converting enzyme inhibition prevents fluid volume expansion in heart transplant recipients.

OBJECTIVES: We sought to test the hypothesis that plasma volume (PV) expansion in heart transplant recipients (HTRs) is caused by failure to reflexively suppress the renin-angiotensin-aldosterone (RAA) axis. BACKGROUND: Extracellular fluid volume expansion occurs in clinically stable HTRs who become hypertensive. We have previously demonstrated that the RAA axis is not reflexively suppressed by a hypervolemic stimulus in HTRs. METHODS: Plasma volume and fluid regulatory hormones were measured in eight HTRs (57+/-6 years old) both before and after treatment with captopril (225 mg/day). Antihypertensive and diuretic agents were discontinued 10 days before. The HTRs were admitted to the Clinical Research Center (CRC), and, after three days of a constant diet containing 87 mEq/day of Na+, PV was measured by using the modified Evans blue dye dilution technique. After approximately four months (16+/-5 weeks), the same HTRs again discontinued all antihypertensive and diuretic agents; they were progressed to a captopril dose of 75 mg three times per day over 14 days, and the CRC protocol was repeated. RESULTS: Captopril pharmacologically suppressed (p<0.05) supine rest levels of angiotensin II (-65%) and aldosterone (-75%). The reductions in vasopressin and atrial natriuretic peptide levels after captopril did not reach statistical significance. The PV, normalized for body weight (ml/kg), was significantly reduced by 12% when the HTRs received captopril. CONCLUSIONS: Extracellular fluid volume is expanded (12%) in clinically stable HTRs who become hypertensive. Pharmacologic suppression of the RAA axis with high-dose captopril (225 mg/day) returned HTRs to a normovolemic state. These findings indicate that fluid retention is partly engendered by a failure to reflexively suppress the RAA axis when HTRs become hypervolemic.

Angiotensin-Converting Enzyme Inhibitors↗