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Biomedical subjects

M J Mitchell

Publications and source records attributed to M J Mitchell.

At least 73 records · Page 4Linked to original sources
PubMed1992

A structural analysis of the Sxr region of the mouse Y chromosome.

Three genetic functions have been mapped to the minute Sxr (sex-reversed) region of the mouse Y chromosome. These are Tdy, the primary testis determinant; Hya, the locus (either structural or regulatory) controlling the expression of the male-specific minor histocompatibility antigen H-Y; and Spy, a spermatogenic gene. Hya and Spy map to DNA deleted from the Sxr region in the deletion variant Sxrb (the delta Sxrb DNA). With the object of cloning Hya and Spy, we initiated chromosome walking in the delta Sxrb DNA. From three independent loci--Sx1, Zf2, and T5--we have isolated approximately 270 kb of delta Sxrb DNA lying in three contigs of 145, 60, and 65 kb, respectively. Within 17 kb of the 3' end of the Zfy-2 gene, lowcopy repeat elements were found in a region that extends for approximately 35 kb. Probes isolated from this region detect multiple Sxr loci, some of which map to the delta Sxrb DNA present in the T5 contig DNA. Three of these multicopy probes detect delta Sxrb loci not represented in our three contigs, which means that six distinct delta Sxrb loci have now been identified. Here we present a preliminary model of the molecular structure of the DNA in this unique region.

Animals↗
PubMed1992

Recombination between the X and Y chromosomes and the Sxr region of the mouse.

The Sxr (sex-reversed) region that carries a copy of the mouse Y chromosomal testis-determining gene can be attached to the distal end of either the Y or the X chromosome. During male meiosis, Sxr recombined freely between the X and Y chromosomes, with an estimated recombination frequency not significantly different from 50% in either direction. During female meiosis, Sxr recombined freely between the X chromosome to which it was attached and an X-autosome translocation. A male mouse carrying the original Sxra region on its Y chromosome, and the shorter Sxrb variant on the X, also showed 50% recombination between the sex chromosomes. Evidence of unequal crossing-over between the two Sxr regions was obtained: using five markers deleted from Sxrb, 3 variant Sxr regions were detected in 159 progeny (1.9%). Four other variants (one from the original cross and three from later generations) were presumed to have been derived from illegitimate pairing and crossing-over between Sxrb and the homologous region on the short arm of the Y chromosome. The generation of new variants throws light on the arrangement of gene loci and other markers within the short arm of the mouse Y chromosome.

Animals↗
PubMed1992

Intranuclear inclusions in the pituitary gland of cynomolgus monkeys.

In a 3-month oral toxicity study of a pharmaceutical agent, intranuclear inclusions were seen in the secretory cells of the pars anterior of the pituitary gland of 22 of 40 cynomolgus monkeys, with similar incidences in control and dosed groups. All monkeys were clinically healthy. Electron microscopic examination revealed that the intranuclear inclusions were cytoplasmic invaginations.

Animals↗
PubMed1992

Ultrasonography-directed native renal biopsy: comparison of an automated biopsy device with a needle system.

The authors compared the performance of an automated biopsy device with a large-bore cutting needle system in ultrasonography-guided native renal biopsy. They retrospectively analysed 52 biopsy specimens from 50 adults with diffuse renal parenchymal disease. Twenty-six consecutive biopsy samples had been obtained manually with a 14-gauge needle (Tru-Cut, Travenol Laboratories, Deerfield, Ill.); a second set of 26 samples had been obtained with a biopsy gun (Bard Biopty, Radiplast, Uppsala, Sweden) fitted with a 14-gauge needle of similar design. The systems were compared in terms of the specimens obtained (the adequacy and the quality of tissue, the number of intact glomeruli and the presence of artifacts) and the incidence of biopsy-related complications. Biopsy specimens obtained with the biopsy gun were judged qualitatively as well as quantitatively superior; they contained an average of 17.6 intact glomeruli, whereas only 11.5 intact glomeruli were retrieved with the needle system. Although the incidence of minor complications was lower after biopsy with the automated gun than after use of the needle system (8% and 15% respectively), two major complications were observed after gun biopsy and none after needle biopsy. The results reported here indicate that for native renal biopsy the Biopty gun delivers a higher-quality tissue core with a lower frequency of minor complications, but not of major complications, than the Tru-Cut needle system.

Adult↗
PubMed1992

Magnetic resonance imaging in the detection of sacroiliitis.

The value of magnetic resonance imaging (MRI) in establishing the diagnosis of sacroiliitis was studied in 20 patients with established or suspected disease on conventional radiographs and in 10 healthy subjects. Coronal T1 weighted, axial T2 weighted and proton density MRI images of the sacroiliac joints in addition to plain film radiographs were obtained. All films were graded from 0 to 4 according to the modified New York criteria and independently for changes in joint width, erosions, sclerosis and ankylosis. Using the modified New York criteria, more abnormalities were detected by MRI than by conventional radiography (p = 0.04). This was due to the detection of definite abnormalities (grades 2-4) by MRI in joints that were graded normal or suspicious (grades 0-1) on plain films (p = 0.01). MRI tended to be superior to plain films in visualizing erosions. Only MRI detected abnormalities of articular cartilage (19 patients) and in subchondral bone marrow (7 patients). The latter 2 types represented fatty infiltration and inflammatory change. Intraobserver and interobserver variation were similar for the interpretation of MRI scans and plain film radiographs. These results suggest that MRI detects changes of established sacroilitis. Due to its ability to directly image articular cartilage it may be particularly useful in patients with early disease.

Adult↗
PubMed1991

Homology of a candidate spermatogenic gene from the mouse Y chromosome to the ubiquitin-activating enzyme E1.

The Sxr (sex-reversed) region, a fragment of the Y chromosome short arm, can cause chromosomally female XXSxr or XSxrO mice to develop as sterile males. The original Sxr region, termed Sxra, encodes: Tdy, the primary sex-determining gene; Hya, the controlling or structural locus for the minor transplantation antigen H-Y; gene(s) controlling the expression of the serologically detected male antigen (SDMA); Spy, a gene(s) required for the survival and proliferation of A spermatogonia during spermatogenesis; Zfy-1/Zfy-2, zinc-finger-containing genes of unknown function; and Sry, which is probably identical to Tdy. A deletion variant of Sxra, termed Sxrb, which lacks Hya, SDMA expression, Spy and some Zfy-2 sequences, makes positional cloning of these genes possible. We report here the isolation of a new testis-specific gene, Sby, mapping to the DNA deleted from the Sxrb region (the delta Sxrb interval). Sby has extensive homology to the X-linked human ubiquitin-activating enzyme E1. The critical role of this enzyme in nuclear DNA replication together with the testis-specific expression of Sby suggests Sby as a candidate for the spermatogenic gene Spy.

Amino Acid Sequence↗
PubMed1991

Studies on the phylogenetic conservation of the SRY gene.

A probe from a conserved motif of the SRY gene (sex-determining region Y), a prime candidate for the human testis-determinant, was hybridized to DNA from 23 species representing 5 vertebrate classes. Hybridization occurred in species with male or female heterogamety, in species with and without sex chromosomes and in those with temperature sex determination. Sex-specific signals were observed only in mammals. Conservation of sequences homologous with SRY through 400 million years of vertebrate evolution would indicate persistence of function. However, if SRY is the primary sex determinant in mammals, it is not clear that it has a similar function, or even one that is sex-related, in nonmammals.

Animals↗
PubMed1990

Detection of thoracolumbar vertebral body destruction with lateral spine radiography. Part I: Investigation in cadavers.

Despite few and inconclusive studies, radiography is generally believed to be insensitive for detection of osteolytic lesions of the spine. A more detailed investigation was undertaken to study the detectability of laboratory-produced osteolytic lesions in cadaveric thoracolumbar vertebral bodies using conventional lateral radiographs. The radiographs were presented to four radiologists in two sessions over a two month period. In the first session, the films were arranged in a composite of five vertebral bodies, T11 to L3 all from the same spine, in which one contained a lesion and the other four were normal. In the second session, each vertebral body film was presented individually. Area (Az) under the receiver-operating characteristic (ROC) curve was used to measure the performances of readers. Observer detection was similar in the two formats with Az ranging from 0.67 +/- 0.05 to 0.79 +/- 0.04 for the composite film arrangement and 0.57 +/- 0.08 to 0.85 +/- 0.10 for the films of individual vertebral bodies. Lesions were grouped into three relative size categories: 18% to 25%, 26% to 40%, and 41% to 60% of transverse vertebral body diameter. The mean increase in ROC area between the small and large lesions was 0.29 (P less than 0.04) for the composite films and 0.16 (P less than 0.05) for the individual films. In the composite study, all readers showed significant (P less than 0.05) increases in lesion detection in spines reflecting large increases (P less than 0.01) in bone mineral content.(ABSTRACT TRUNCATED AT 250 WORDS)

Cadaver↗
PubMed1990

Detection of thoracolumbar vertebral body destruction with lateral spine radiography. Part II: Clinical investigation with computed tomography.

Conventional radiography in the lateral projection was used to evaluate 25 osteolytic lesions involving vertebral bodies of the thoracolumbar spine. Destruction was calculated as percentages of the maximum transverse diameter and volume of the vertebral body as measured by computed tomography (CT) and the effect of size of lesion on detection was evaluated. Areas (Az) under the receiver-operating characteristic (ROC) curves and the significance of differences were determined from the observations of four radiologists. The mean difference between areas under the ROC curve for lesions involving 32% to 60% of the transverse diameter and for larger lesions of 61% to 93% was 0.12 and significant (P less than 0.05). The effect of the presence of localized loss of vertebral body density, sclerotic bone tissue surrounding the lesion and cortical destruction was evaluated in a second session, in films with lesions the observers scored 4 (probably abnormal) or 5 (definitely abnormal). Cortical destruction was reported to be helpful for detection in 35% of lesions, sclerotic bone surrounding the lesions was helpful in 30%, and a qualitative local decrease in bone density was noted in all lesions. In comparison with the results obtained for the same four observers with experimentally produced lesions in our previous cadaveric study, the clinical lesions of comparable size were not as readily detected. The ROC area for the largest group of clinical lesions (61% to 93%, Az = 0.83 +/- 0.07) was not significantly different from that for a group of smaller cadaveric lesions (41% to 60%, Az = 0.83 +/- 0.05). The smaller clinical lesions (32% to 60%, Az = 0.71 +/- 0.08) were similar in detectability to the experimental lesions of relative diameter 26% to 40% (Az = 0.74 +/- 0.15). Caution should be exercised in the interpretation of conventional radiographs in the lateral projection if there is suspicion of vertebral body destruction.

Adult↗
PubMed1990

A double-blind comparative study of remoxipride and thioridazine in the acute phase of schizophrenia.

Sixty-one patients with acute schizophrenia received either remoxipride (75-375 mg daily) or thioridazine (150-750 mg daily) for 6 weeks. There was no statistically significant between-drug difference in improvement in mental state, as measured by the Brief Psychiatric Rating Scale, although the trend favoured thioridazine; global assessment of illness severity at the last rating also favoured thioridazine. Sedation, anticholinergic effects, autonomic dysfunction, and weight gain were significantly more common in patients receiving thioridazine. Both drugs produced few extrapyramidal effects, but both were associated with cardiovascular changes in two patients; neither drug produced significant abnormalities in laboratory tests.

Acute Disease↗
PubMed1990

Cauda equina syndrome complicating ankylosing spondylitis.

The cauda equina syndrome is an uncommon and poorly understood complication of ankylosing spondylitis. The clinical and radiologic findings in five patients with this syndrome are described. Typical findings include cutaneous sensory impairment of the lower limbs and perineum with sphincter disturbances. Motor impairment occurs less frequently, and associated pain is an inconstant feature. Enlargement of the caudal sac and dorsal arachnoid diverticula that erode the lamina and spinous processes are characteristic myelographic and computed tomographic findings. The pathogenesis of the cauda equina syndrome in ankylosing spondylitis remains unknown but may be due to demyelination, post-irradiation ischemia, or compression from spinal arachnoiditis.

Adult↗
PubMed1989

Ouabain binding in the human brain. Effects of Alzheimer's disease and aging.

We studied Na+,K+-adenosine triphosphatase by assaying specific tritiated ouabain binding in the frontal cortex, temporal cortex, hippocampus, putamen, cerebellum, and cerebral microvessels in subjects with Alzheimer's disease and control subjects. Ouabain binds specifically, in a saturable manner, and with a high affinity to a single class of binding sites in all the tissues studied. The density of ouabain binding sites was highest in cerebellum and frontal cortex (approximately 40 pmol/mg of protein); intermediate in temporal cortex, hippocampus, and putamen; and lowest in brain microvessels (approximately 8 pmol/mg of protein). The dissociation constant of binding was about 30 nmol/L in all tissues. In control subjects, there were no age-related alterations in ouabain binding, nor was there any correlation between ouabain binding and postmortem delay. However, there was a marked decrease in brain ouabain binding in subjects with Alzheimer's disease when compared with age-matched controls, especially in the cerebral cortex. Ouabain binding was also significantly decreased in the cerebellum and putamen of subjects with Alzheimer's disease even though these brain regions are not particularly affected in this disease. Ouabain binding to brain microvessels, which constitute the blood-brain barrier, was not significantly decreased in subjects with Alzheimer's disease. The decreased specific ouabain binding in the brain of subjects with Alzheimer's disease probably reflects the loss of neuronal membranes.

Adult↗
PubMed1989

Selective potent restriction of P450b- but not P450e-dependent 7,12-dimethylbenz[a]anthracene metabolism by the microsomal environment.

The prototypic members of the rat liver cytochrome P450IIB subfamily, P450b and P450e, differ by only 13 amino acids and yet purified P450b is considerably more active than P450e for all known substrates. A unique regioselectivity difference between cytochromes P450b and P450e for the metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) and a genetic deficiency in P450e expression in the Marshall (M520/N) rat strain have been exploited to determine the microsomal contributions of the respective forms toward the metabolism of DMBA. The total contribution to metabolism by each isozyme has been assessed based on the sensitivity to rabbit anti-P450b/e IgG and comparison with microsomal P450b and P450e content as measured by Western blots. Liver microsomes from untreated M520/N rats do not express detectable levels of P450e but express P450b at a level that is 2-fold higher than that of P450e in liver microsomes from untreated F344 rats (50 pmol/mg). However, only 4% of the constitutive DMBA metabolizing activity of liver microsomes from the M520/N rat strain could be inhibited by anti-P450b/e IgG. A 30-fold induction of hepatic P450b by phenobarbital (PB) was also completely ineffective in increasing P450b-dependent DMBA metabolism. PB treatment had no appreciable effect on either the levels of expression of P450b protein or P450b-dependent DMBA metabolism, in M520/N lung and adrenal microsomes. In contrast, PB treatment of F344 rats considerably increased P450b/e-dependent metabolism by liver, lung, and adrenal microsomes. The regioselectivity of the anti-P450b/e-sensitive metabolism (predominantly 12-methyl hydroxylation), however, indicated a much greater contribution from P450e than P450b in every tissue examined despite a several fold higher expression of P450b than of P450e. P450b was expressed constitutively in lung microsomes from both strains but again failed to exhibit appreciable DMBA metabolizing activity. Based on these activities and microsomal P450b contents, P450b consistently exhibited turnover numbers (0.02-0.15 nmol/nmol P450b/min) that were at least 10-fold lower than those of pure P450b. In contrast, the calculated turnover numbers for microsomal P450e were consistently comparable to those of pure P450e (approximately 1 nmol/nmol P450e/min).

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Diagnostic imaging of lower extremity trauma.

Traumatic injuries to the lower extremity are a common occurrence in today's society and may result in significant morbidity and mortality if not appropriately treated. Adequate radiographic evaluation is crucial to the assessment of these injuries. This article reviews the radiographic features and imaging approaches to the commonly encountered injuries of the lower extremity.

Femoral Fractures↗
PubMed1989

A comparison of felodipine and nifedipine as monotherapies for the treatment of mild to moderate hypertension.

We conducted a randomised double-blind crossover comparison of felodipine, 10 mg once daily, nifedipine 20 mg twice daily, each treatment being given as a monotherapy for four weeks. Active treatment was preceded by a two-week placebo run-in. Both systolic (SBP) and diastolic (DBP) blood pressures (supine and erect) fell significantly (all P less than 0.001) following both drug treatments. Nifedipine produced a greater orthostatic effect, and hence a significantly greater fall in erect SBP than felodipine (P less than 0.05). There was no significant difference between the effects of the drugs on DBP. Achieved DBP was 90 mmHg or less in 18/22 patients on felodipine and 18/22 patients on nifedipine. Both drugs were well-tolerated. Felodipine given once daily was effective as a monotherapy for the control of mild to moderate hypertension and compared favourably with twice daily nifedipine.

Adult↗