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Biomedical subjects

M J Thomson

Publications and source records attributed to M J Thomson.

At least 19 recordsLinked to original sources

Mapping quantitative trait loci for yield, yield components and morphological traits in an advanced backcross population between Oryza rufipogon and the Oryza sativa cultivar Jefferson.

An advanced backcross population between an accession of Oryza rufipogon (IRGC 105491) and the U.S. cultivar Jefferson (Oryza sativa ssp. japonica) was developed to identify quantitative trait loci (QTLs) for yield, yield components and morphological traits. The genetic linkage map generated for this population consisted of 153 SSR and RFLP markers with an average interval size of 10.3 cM. Thirteen traits were examined, nine of which were measured in multiple environments. Seventy-six QTLs above an experiment-wise significance threshold of P<0.01 (corresponding to an interval mapping LOD>3.6 or a composite interval mapping LOD>3.9) were identified. For the traits measured in multiple environments, 47% of the QTLs were detected in at least two environments. The O. rufipogon allele was favorable for 53% of the yield and yield component QTLs, including loci for yield, grains per panicle, panicle length, and grain weight. Morphological traits related to the domestication process and/or weedy characteristics, including plant height, shattering, tiller type and awns, were found clustered on chromosomes 1 and 4. Comparisons to previous studies involving wild x cultivated crosses revealed O. rufipogon alleles with stable effects in multiple genetic backgrounds and environments, several of which have not been detected in studies between Oryza sativa cultivars, indicating potentially novel alleles from O. rufipogon. Some O. rufipogon-derived QTLs, however, were in similar regions as previously reported QTLs from Oryza sativa cultivars, providing evidence for conservation of these QTLs across the Oryza genus. In addition, several QTLs for grain weight, plant height, and flowering time were localized to putative homeologous regions in maize where QTLs for these traits have been previously reported, supporting the hypothesis of functional conservation of QTLs across the grasses.

Chromosome Mapping↗

Genome evolution of tobacco mosaic virus populations during long-term passaging in a diverse range of hosts.

The effects of host changes on plant virus genome evolution was studied by nucleotide sequencing. A single tobacco (Nicotiana tabacum cv. Xanthi) plant was inoculated with in vitro transcripts from a plasmid clone of tobacco mosaic tobamovirus (TMV). This initial viral population was then transferred 11-12 times in parallel populations in 7 plant host species (1-4 replicates each) over a period of 413-515 days. Virion RNA was then isolated, reverse transcribed, amplified, cloned in bacteria, and sequenced. Portions of the coat protein, movement protein, and replicase genes were sequenced. Fourteen unique mutations were detected from a total of 188 clones (35,607 bases) sequenced, indicating a relatively small overall mutation rate of 3.1 x 10(-4) nucleotide substitutions/base-year. A small Ka/Ks value of 0.09 was also found, indicating selection against amino acid changes. Eighty-five percent of the substitutions were transitions. A G'(ST) value of 0.7 for the coat protein gene suggested that host type affected sequence changes in this region of the genome, but chi(2) analysis did not support this conclusion. This is the first study using sequencing to compare representative sample sections of a plant viral genome following a major selective disturbance such as extended passaging in an alternate host.

Genome, Viral↗

Hansen type I disk disease at T1-2 in a dachshund.

A 7-year-old Dachshund was presented with chronic left thoracic limb lameness and acute neurological deficits to the hind limbs following trauma. A lesion was suspected between C7 and T2 on the basis of neurological examinations. Radiography and myelography identified a calcified intervertebral disk at C7-T1 and an extradural unilateral compressive lesion at T1-2. Computed tomography scans of the cranial thoracic spine revealed extrusion of disk material from the T1-2 intervertebral space resulting in marked spinal cord compression. Intervertebral disk disease is rarely reported at this location. The neurological condition deteriorated after a second myelogram, which was done to examine the thoracolumbar spine. A modified dorsal decompression of T1-2 was performed. The dog was euthanased due to further neurological deterioration 8 days after surgery.

Animals↗

Angiotensin-converting enzyme genotypes and risk for myocardial infarction in women.

OBJECTIVES: We tested for an association between the angiotensin-converting enzyme (ACE) DD polymorphic genotype and myocardial infarction (MI) in a sample group composed exclusively of women. BACKGROUND: The human ACE gene occurs with either an insertion (I allele) or a deletion (D allele) of a 287-base pair (bp) Alu element. Part of the variance in serum ACE levels may be accounted for by this polymorphism. Also, the DD genotype has been associated with an increased risk of MI in predominantly male populations. However, the risk in women is poorly defined. METHODS: Genomic DNA was extracted from buffy coat blood using a phenol/chloroform method. Angiotensin-converting enzyme alleles were identified using primers to bracket the insertion region in intron 16. Amplification using polymerase chain reaction allowed identification of a 490-bp (I allele) or a 190-bp (D allele) product, or both. RESULTS: Allelic and genotypic frequencies in control subjects were similar to those reported in mostly male populations, and frequencies of genotypes were in the Hardy-Weinberg equilibrium. In contrast, the distribution of genotypes in patients with MI diverged from the equilibrium. Specifically, DD genotypic frequency was increased in women with (n = 141) versus without (n = 338) a previous MI (39% vs. 29%, odds ratio [OR] 1.54, 95% confidence interval 1.02 to 2.32, p < 0.04). Risk was particularly increased in women <60 years old (OR 2.04, p < 0.05). In contrast, the DD genotype did not predict angiographic coronary artery disease. CONCLUSIONS: Consistent with findings in male-dominated populations, a modest association of the ACE DD genotype with MI was found in women. The basis for this association requires further study.

Aged↗

A mutation in the methylenetetrahydrofolate reductase gene is not associated with increased risk for coronary artery disease or myocardial infarction.

OBJECTIVES: We sought to determine whether the C677T transition in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased risk for coronary artery disease (CAD) or myocardial infarction (MI). BACKGROUND: Elevated plasma homocysteine has been identified as a risk factor for coronary atherosclerosis. Homocysteinemia may result from deficient MTHFR activity. A thermolabile form of MTHFR, associated with a C677T genetic transition, shows reduced activity and may be a risk factor for CAD. METHODS: Blood was withdrawn from patients undergoing coronary angiography, and DNA was extracted by a phenol-chloroform method. Genotyping was done by polymerase chain reaction (PCR) amplification of a 198-base pair segment of the MTHFR gene that brackets nucleotide 677. The amplicon was digested with the HinfI restriction enzyme. Products were visualized after electrophoresis in 1.5% agarose with ethidium bromide. RESULTS: Among 200 patients with a diagnosis of MI, the polymorphic allelic frequency was 33.3%, compared with 32.1% among 554 control subjects (p = 0.68); homozygosity was present in 11.5% of patients and 10.6% of control subjects (p = 0.74, odds ratio [OR] 1.09, 95% confidence interval [CI] 0.63 to 1.82). Among 510 patients with severe CAD (>60% stenosis), allelic frequency was 32.0%, compared with 34.8% for 168 subjects without CAD (<10% stenosis, p = 0.33); 11.2% of patients with CAD compared with 13.1% of control subjects were homozygous (p = 0.50, OR 0.83, 95% CI 0.5 to 1.40). CONCLUSIONS: Patients with angiographic evidence of CAD or clinical MI do not show an increased frequency of the C677T transition in the MTHFR gene. Our findings do not support this polymorphism as a risk factor for CAD or MI in a predominantly white, well nourished population of unrestricted age.

Adult↗

Development of insulin resistance in 3T3-L1 adipocytes.

Insulin resistance is a manifestation of both diabetes mellitus and obesity. However, the mechanism is still not clearly identified. Herein, we describe a procedure that allows us to evaluate the development of insulin resistance in 3T3-L1 adipocytes. Under these conditions, we show that the concentration of insulin required for 50% desensitization of glucose transport activity is 100 pM; maximal desensitization could be achieved with 1 nM. This demonstrates for the first time that 3T3-L1 adipocytes develop insulin resistance in response to physiologically relevant concentrations of insulin. Glucose (or glucosamine), in addition to insulin, was required to establish desensitization. The expression of GLUT4 protein decreased by 50% with exposure to 10 nM insulin. The dose-dependent loss of GLUT4 was similar to the dose dependence for insulin-resistant transport activity. Translocation in the presence of acute insulin was apparent, but the extent of recruitment directly reflected the decrease in GLUT4 protein. GLUT4 mRNA also declined, but the ED50 was approximately 5 nM. Together, these data suggest that the loss of GLUT4 protein likely underlies the cause of desensitization. However, the loss of GLUT4 protein did not correlate with the loss in GLUT4 mRNA suggesting post-translational control of GLUT4 expression.

3T3 Cells↗

Management of a femoral fracture complicated by clostridial myositis.

A clinical case of clostridial myositis secondary to a comminuted femoral fracture is described. This case is unusual because, despite the severe degree of obvious muscle necrosis and gas production, the dog had minimal signs of systemic toxicity. Union of the fracture was achieved but six months postoperatively muscular contracture had resulted in permanent stifle extension.

Animals↗

Increased incidence of Chlamydia species within the coronary arteries of patients with symptomatic atherosclerotic versus other forms of cardiovascular disease.

OBJECTIVES: The objectives of this study were to test prospectively for an association between Chlamydia and atherosclerosis by comparing the incidence of the pathogen found within atherosclerotic plaques in patients undergoing directional coronary atherectomy with a variety of control specimens and comparing the clinical features between the groups. BACKGROUND: Previous work has suggested an association between Chlamydia pneumoniae infection and coronary atherosclerosis, based on the demonstration of increased serologic titers and the detection of bacteria within atherosclerotic tissue, but this association has not yet been regarded as established. METHODS: Coronary specimens from 90 symptomatic patients undergoing coronary atherectomy were tested for the presence of Chlamydia species using direct immunofluorescence. Control specimens from 24 subjects without atherosclerosis (12 normal coronary specimens and 12 coronary specimens from cardiac transplant recipients with subsequent transplant-induced coronary disease) were also examined. RESULTS: Coronary atherectomy specimens were definitely positive in 66 (73%) and equivocally positive in 5 (6%), resulting in 79% of specimens showing evidence for the presence of Chlamydia species within the atherosclerotic tissue. In contrast, only 1 (4%) of 24 nonatherosclerotic coronary specimens showed any evidence of Chlamydia. The statistical significance of this difference is a p value < 0.001. Transmission electron microscopy was used to confirm the presence of appropriate organisms in three of five positive specimens. No clinical factors except the presence of a primary nonrestenotic lesion (odds ratio 3.0, p = 0.057) predicted the presence of Chlamydia. CONCLUSIONS: This high incidence of Chlamydia only in coronary arteries diseased by atherosclerosis suggests an etiologic role for Chlamydia infection in the development of coronary atherosclerosis that should be further studied.

Aged↗

Osteochondrosis of the elbow: a review of the pathogenesis and a new approach to treatment.

To test the hypothesis that joint incongruity contributes to the pathogenesis of elbow osteochondrosis, the left and right radius and ulna of 20 young large breed dogs were measured to determine any variation in length and to observe any incongruity of the elbow joint. Both lame and normal dogs were included in the study. Nine of the 20 dogs had marked disparity in radial and ulnar lengths yet only one had obvious elbow joint incongruity. The use of a sliding osteotomy for the treatment of fragmented coronoid process and a lengthening osteotomy for the treatment of an ununited anconeal process is also discussed. All four dogs treated with a sliding osteotomy showed a marked clinical improvement, and two of the three dogs treated with a lengthening osteotomy showed radiographic fusion of the anconeal process.

Animals↗

Glycolysis compared in intact, permeabilized and sonicated L-929 cells.

The effects of incubation time and cell density on glycolytic rate were examined in suspensions of intact, permeabilized and sonicated L-929 cells. Sonicates exhibited strong dependence on cell density and a distinct lag in glycolytic rate, while intact cells showed no cell density dependence and linear glycolytic rates. Permeabilized cells exhibited linear glycolytic rates, but sometimes showed dependence on cell density. Rates of lactate production (nmol at 30 min/10(6) cells) were highest in sonicates and lowest in intact cells. These results are interpreted as support for the previously proposed hypothesis that enzymes of the glycolytic pathway are highly organized in intact L-929 cells.

Animals↗

Double-blind, randomized comparison of 24 weeks of norfloxacin and 12 weeks of norfloxacin followed by 12 weeks of placebo in the therapy of complicated urinary tract infection.

We evaluated the benefits of prolonging norfloxacin therapy from 12 to 24 weeks for complicated urinary tract infection in a double-blind, randomized, placebo-controlled study. During the second 12 weeks, norfloxacin was superior to placebo (P less than 0.05) in suppressing bacteriuria. Adverse effects were common but mostly confined to the initial 12 weeks.

Bacteriuria↗

Cefoxitin plus tobramycin and clindamycin plus tobramycin. A prospective randomized comparison in the therapy of mixed aerobic/anaerobic infections.

The efficacy of therapy with cefoxitin sodium plus tobramycin sulfate, with the tobramycin therapy discontinued if no cefoxitin-resistant pathogens grew from appropriate cultures, was compared with clindamycin phosphate plus tobramycin therapy in mixed aerobic/anaerobic intra-abdominal and female pelvic infections. Of 96 evaluable patients, 39 (76%) of 51 randomized to cefoxitin and 38 (84%) of 45 randomized to clindamycin were cured and an additional seven (14%) of 51 and three (6.7%) of 45, respectively, were improved. Bacteroides fragilis "group" was isolated from 44 (54%) of 82 patients with appropriate specimens. Duration of aminoglycoside therapy was significantly shorter in patients randomized to cefoxitin and tobramycin (mean, 4.1 +/- 1.8 days vs 7.0 +/- 3.2 days). There was a tendency to greater nephrotoxic reactions in patients randomized to clindamycin and tobramycin. We conclude that cefoxitin plus tobramycin with selective early discontinuation of aminoglycoside therapy is an acceptable regimen for the therapy of mixed aerobic/anaerobic infections.

Adolescent↗

7-Aroyl-2,3-dihydrobenzo[b]furan-3-carboxylic acids and 7-benzoyl-2,3-dihydrobenzo[b]thiophene-3-carboxylic acids as analgesic agents.

The synthesis of a series of 7-aroyl-2,3-dihydrobenzo[b]furan-3-carboxylic acids and 7-benzoyl-2,3-dihydrobenzo[b]thiophene-3-carboxylic acids is described. The isomeric 4-benzoyl-1,3-dihydrobenzo[c]furan-1-carboxylic acid was also prepared. Compounds were evaluated for analgesic activity in the mouse phenyl-p-quinone-induced writhing test. Selected compounds were tested for their ability to produce gastric damage in fasted mice and for inhibition of prostaglandin synthetase activity in vitro. Zomepirac was used as a reference. Structure-activity relationships are discussed. One of the compounds, 7-benzoyl-5-chloro-2,3-dihydrobenzo[b]furan-3-carboxylic acid (2c), combined potent analgesic activity with low gastric irritancy.

Analgesics↗

The effect of adjuvant arthritis on the subsequent local inflammatory response in rats.

An assessment was made of the cellular inflammatory response to the subcutaneous implantation of sterile nitrocellulose discs and polyvinyl sponges in both normal rats and rats with adjuvant-induced arthritis. It was found that from 3 days after adjuvant injection the treated animals exhibited a reduced accumulation of inflammatory cells onto the nitrocellulose discs and that this impairment in response was not apparent until the discs had been retained for longer than 24 h. When discs were implanted after non-arthritogenic doses of adjuvant constituents or injection of brewer's yeast no effect was seen on the subsequent response. When polyvinyl sponges were used in adjuvant-treated animals a similar initial reduction in cellular accumulation was observed, which was later followed by increased cell numbers associated with enhanced granuloma formation. Differential cell counts revealed that both neutrophil and mononuclear cell types were affected. Some of the possible mechanisms involved in these observations are discussed.

Animals↗

BRL 20459, a novel topically active non-steroidal anti-inflammatory drug.

BRL 20459 is a novel compound which displays anti-inflammatory activity when applied topically in the croton oil and cantharadin rat ear inflammation models. The compound does not inhibit uv-induced erythema in the guinea-pig or granuloma formation in the cotton pellet test in the rat. BRL 20459 does not inhibit prostaglandin synthesis nor does it interact with corticosteroid receptors in the thymus. In contrast to hydrocortisone, BRL 20459 did not cause thymus involution or reduce body weight gain in rats. BRL 20459 would seem to have a different mechanism of action to hydrocortisone, but this mechanism is as yet unknown.

Administration, Topical↗

Comparative trial of norfloxacin and trimethoprim-sulfamethoxazole in the treatment of women with localized, acute, symptomatic urinary tract infections and antimicrobial effect on periurethral and fecal microflora.

Forty-three women with acute, symptomatic urinary tract infections were randomized to receive either norfloxacin (400 mg) twice daily or trimethoprim-sulfamethoxazole (160-800 mg) twice daily for 10 days. Of the 43 patients, 7 (16%) had low-count bacteriuria and pyuria and were included in the evaluation. Escherichia coli was isolated in 72% of the infections, whereas coagulase-negative staphylococci were isolated in 14%. All isolates were susceptible to the assigned study drug. The MICs for 90% of the strains susceptible to norfloxacin and trimethoprim-sulfamethoxazole were less than or equal to 2 and less than or equal to 0.8-16 micrograms/ml, respectively. The cure rates for norfloxacin and trimethoprim-sulfamethoxazole were 95 and 90%, respectively. There were 17 patients with presumptive upper tract infections; only 1 of these relapsed after therapy. The effects on the periurethral flora were similar in both groups, but the infecting organism was eradicated from the fecal flora in 93% of the patients treated with norfloxacin and in 57% of the patients treated with trimethoprim-sulfamethoxazole. More early reinfections occurred in the trimethoprim-sulfamethoxazole group, with resistant organisms appearing in urine and in the periurethral and fecal flora in all cases. Three patients in each group experienced adverse clinical effects, but these were more severe in the trimethoprim-sulfamethoxazole group. No adverse hematological or biochemical changes were noted. From these results, we concluded that norfloxacin is at least as effective as trimethoprim-sulfamethoxazole in the therapy of acute, symptomatic urinary tract infections in women.

Acute Disease↗