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Biomedical subjects

B Mitchell

Publications and source records attributed to B Mitchell.

At least 19 recordsLinked to original sources
PubMed1992

Failed self-tolerance and autoimmunity in IgG anti-DNA transgenic mice.

Transgenic mice were generated that express both the H and L chain genes derived from a hybridoma secreting an IgG2a mAb specific for ds- and ssDNA. This hybridoma is derived from a lupus mouse and can accelerate nephritis in young NZB x NZW F1 female mice and induce clinical nephritis in BALB/c mice. Some transgenic B cells did not exhibit allelic exclusion; they expressed both transgene-derived IgG and endogenous IgM intracellularly. Most of the B cells in transgenic mice expressed endogenous IgM, some of them expressed low levels of IgG on cell membranes. The transgenic mice, created in a strain not prone to SLE, expressed elevated serum IgG anti-DNA, and some developed clinical nephritis. The affinity of the spontaneously secreted IgG antibodies for dsDNA were similar in nephritic NZB x NZW F1 and transgenic mice. In contrast to the nontransgenic littermates, immunization of transgenic mice with murine DNA further enhanced serum levels of IgG anti-DNA in transgenic mice. Therefore, expression of transgene-encoded IgG anti-DNA mainly in the secreted form does not provide the signals necessary for allelic exclusion or self-tolerance. Expression of this Ig is sufficient to induce a mild form of autoimmune disease.

Animals↗
PubMed1992

Prostate adenocarcinoma using Gleason scores correlates with prostate-specific antigen and prostate acid phosphatase measurements.

To evaluate a relationship between Gleason scores of histopathology of prostate carcinoma and concurrent serum prostate-specific antigen (PSA) and prostate acid phosphatase (PAP) values, 65 men with prostate carcinoma were studied. These patients' cumulative Gleason scores were obtained by totaling the primary and secondary patterns, resulting in two groups: 42 patients received high (6-10) and 23 received low (2-5) Gleason scores. Serum PSA and PAP values were measured by radioimmunometric assay 1 to 7 days before surgical procedures or biopsy for prostate carcinoma. Mean serum PSA for patients in the high Gleason score group was 134.39 ng/mL (normal range: 0 to 4), and the mean serum PSA for patients in the low Gleason score group was 23.62 ng/mL. Mean serum PAP for patients with high scores was 28.08 ng/mL (normal range: 0 to 5), and the mean serum PAP for patients with low scores was 18.19 ng/mL. Patients with high Gleason scores showed significantly greater elevation of serum PSA than those with low Gleason scores (P = .047), using two samples to test for groups having unequal variants. Prostate acid phosphatase levels of patients with high scores were not significantly higher than the levels in patients with low scores (P = .60). These results indicate that PSA levels but not PAP levels correlate with Gleason scores.

Acid Phosphatase↗
PubMed1991

Prediction of radionuclide bone imaging findings by Gleason histologic grading of prostate carcinoma.

To evaluate a relationship between Gleason scores and Tc-99m HMDP bone imaging findings, data from 48 men (aged 45 to 77; mean, 67) with prostate carcinoma who had a bone imaging study at the time of presentation were reviewed. Cumulative Gleason scores were divided into two groups: high scores (6-10), 32 men; low scores (2-5), 16 men. Of the 32 men with high Gleason scores, 15 tested positive for multiple metastases and 17 tested negative. Tumors of the 16 men with low Gleason scores were negative for metastasis. A chi-square association between Gleason scores and the presence of metastases, either of a superscan pattern or multiple metastases, was 10.9 (1 df, P less than 0.001). The results indicate that a superscan pattern or multiple metastases were found exclusively in the bone images of patients with high histologic grades; bone images negative for metastases were associated with low-grade tumors. We conclude that positive bone imaging for metastases at the initial scan occurs only in patients who have high Gleason scores, that patients with high Gleason scores might or might not have skeletal metastasis, and that skeletal metastasis is not predictable in patients with low Gleason scores.

Adenocarcinoma↗
PubMed1990

Lesions of nonvisual inputs affect plasticity, norepinephrine content, and acetylcholine content of visual cortex.

1. The depletion of both norepinephrine (NE) and acetylcholine (ACh) in the visual cortex can decrease plasticity. This decrease in plasticity, although dramatic under some circumstances, fails to occur under others. 2. We depleted cortical NE and ACh in 35- to 42-day-old kittens by making a lesion of the white matter behind the cingulate gyrus. One eye was sutured on the day of the lesion. We recorded from the visual cortex 7 days or 2-3 mo later and used the influence of the deprived eye on the cortical cells as a measure of plasticity. 3. We measured NE content by high-pressure liquid chromatography (HPLC) and inferred ACh depletion from depletion of choline acetyltransferase (ChAT) activity. NE depletion averaged 60% in the successfully depleted animals. Depletion of ChAT activity was consistent with NE depletion. 4. When recording occurred 7 days after the lesion and the sutured eye was contralateral to the lesion, plasticity was decreased on the side with the lesion; 70% of the cells were driven by the deprived eye. On the control, uninjured side only 15% of the cells were driven by the deprived eye. 5. In two circumstances the lesion did not cause a decrease in plasticity. In animals with suture ipsilateral to the lesion, the cortex remained plastic. In these animals only 26% of the cells in the hemisphere with the lesion were driven by the deprived eye. The cortex also retained its plasticity if the contralateral eye remained sutured for several months after the lesion, even though there was no recovery from NE and ACh depletion. 6. We conclude that depletion of NE and ACh does decrease plasticity; that is, it protects the deprived eye from losing its ability to drive cortical cells, at least for a short period of time. Depletion protects only the normally dominant contralateral pathway; the ipsilateral visual pathway remains plastic. 7. Perhaps the importance of the side of the deprived eye can be explained by assuming that depletion of NE and ACh removes facilitatory input. This would decrease the ability of cortical cells on the side with lesion to potentiate the input from the nondeprived eye relative to the deprived eye; that is, it would decrease the molecular deprivation (MD) effect. A removal of facilitation would also increase the visual input required to drive cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1989

Effect of cisapride on postprandial gastro-oesophageal reflux.

We studied the effect of cisapride on oesophageal motor function and postprandial gastro-oesophageal reflux in a randomised, double blind, placebo controlled crossover study. In 16 patients with symptomatic gastro-oesophageal reflux, cisapride 10 mg orally and placebo were studied on separate days according to identical protocols. Cisapride and placebo were given 30 minutes before a standard meal. Each study day was preceded by corresponding three day oral loading of cisapride (10 mg tds) or placebo. Lower oesophageal sphincter pressure, oesophageal body motility and oesophageal pH were monitored for 30 minutes before and three hours after the meal. Plasma cisapride concentrations were measured before and after dosing on both study days. With cisapride treatment, the plasma cisapride levels ranged from 48.1 (5.0) to 75.9 (6.9) ng/ml. Plasma levels were undetectable during placebo treatment. Cisapride enhanced acid clearance but had no significant effect on the duration of acid exposure, the rate of reflux episodes, the pattern of lower oesophageal sphincter pressure associated with the reflux episodes, basal lower oesophageal sphincter pressure or oesophageal peristalsis. These findings do not suggest a major role for cisapride, at the dosage tested, for the control of troublesome postprandial gastro-oesophageal reflux.

Adult↗
PubMed1988

Clinical aspects of diabetic neuropathies.

Diabetic neuropathy is a common complication of diabetes that may be associated both with considerable morbidity (painful polyneuropathy, neuropathic ulceration) and mortality (autonomic neuropathy). The epidemiology and natural history of diabetic neuropathy is clouded with uncertainty, largely due to confusion in the definition and measurement of this disorder. We have reviewed a variety of the clinical manifestations associated with somatic and autonomic neuropathy and discussed current views related to the management of the different abnormalities. Although unproven, the best evidence suggests that near normal control of blood glucose in the early years following onset of diabetes may help delay the development of clinically significant nerve impairment. Intensive therapy to achieve normalization of blood glucose may also lead to reversibility of early diabetic neuropathy, but again this is unproven. Our ability to manage successfully the many different manifestations of diabetic neuropathy depends ultimately on our success in uncovering the pathogenic processes underlying this disorder. The recent resurgence of interest in the vascular hypothesis, for example, has opened up new avenues of investigation for therapeutic intervention. Paralleling our increased understanding of the pathogenesis of diabetic neuropathy, there must be refinements in our ability to measure quantitatively the different types of defects that occur in this disorder. These tests must be validated and standardized to allow comparability between studies and more meaningful interpretation of study results.

Diabetes Mellitus, Type 1↗
PubMed1988

Healing and relapse of severe peptic esophagitis after treatment with omeprazole.

We have studied the response of erosive or ulcerative esophagitis to treatment with omeprazole and its subsequent relapse on cessation of therapy in 196 patients. In the first phase of the study omeprazole (20 or 40 mg daily) was compared with placebo in 64 patients. After 4 wk there was endoscopic healing in 81% (25 of 31) of omeprazole-treated patients and in only 6% (2 of 32) of placebo-treated patients. Endoscopic healing of esophagitis was accompanied by symptom relief and histologic healing of ulceration. In the second (dose finding) phase a further 132 patients were randomized to omeprazole (20 or 40 mg daily) and endoscopic healing was assessed. In patients with the mildest grade of ulcerative esophagitis (grade 2), healing occurred at 4 wk in 87% receiving 20 mg and in 97% receiving 40 mg. In patients with grade 3 esophagitis, 67% (20 mg) and 88% (40 mg) were healed. Less than half the patients with grade 4 esophagitis (Barrett's ulcers or confluent ulceration) healed with either 20 mg (48%) or 40 mg (44%). Regression analysis in the 164 omeprazole-treated patients showed no evidence that healing was influenced by factors other than severity of esophagitis at entry and omeprazole dose. In phase 3 of the study the rate of endoscopic relapse was determined in 107 endoscopically healed patients after stopping omeprazole. Erosive or ulcerative esophagitis recurred in 88 of 107 (82%) by 6 mo. Neither initial dose, grade of esophagitis, nor smoking was shown to influence relapse rate. Omeprazole is a highly effective treatment for peptic esophagitis. The 40-mg/day dosage produces endoscopic healing slightly more quickly than the 20-mg/day dosage, and the initial endoscopic gradings are of prognostic value. Relapse occurs rapidly when treatment is stopped.

Adult↗
PubMed1986

Idiopathic crescentic membranous glomerulonephritis.

A case of idiopathic crescentic membranous glomerulonephritis is reported. In addition to the present case, eight cases of this type of glomerulonephritis reported in the literature are reviewed. This is an uncommon form of glomerulonephritis, seen in middle age and in both sexes. Clinical presentation is similar to idiopathic membranous nephropathy. Lupus and antiglomerular-basement membrane nephritis should be excluded by serological tests. Prognosis is grave, resulting in end-stage renal failure (ESRD) within a year in most patients. There is no specific therapy known to alter the course of the disease. In this patient, short courses of high-dose corticosteroids, administered during flares of glomerulonephritis, seemed to improve renal function.

Adolescent↗
PubMed1986

Renal function in the obese Zucker rat.

The hyperphagic, genetically obese Zucker rat (fa/fa) exhibits both a greater kidney size and a progressive, premature glomerular sclerosis. In the present study, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and renal tubular function were evaluated during study 1 in lean Zucker (FA/-), fa/fa, and lean Sprague-Dawley (S-D) rats. The GFR as measured by renal inulin clearance (ClIN) was not significantly different (P greater than 0.05) between S-D (1.36 +/- 0.18 ml/min) vs FA/- (1.36 +/- 0.33 ml/min) and FA/- vs fa/fa (1.25 +/- 0.42 ml/min). The ERPF as measured by renal p-aminohippurate (PAH) clearance (ClPAH) also was not significantly different between S-D (3.98 +/- 0.80 ml/min) vs Fa/- (3.71 +/- 0.81 ml/min) and Fa/- vs fa/fa (3.34 +/- 1.60 ml/min). There was a significant difference (P less than 0.05) in the renal tubular transport maximum (Tm) of PAH between S-D (2.23 +/- 0.40 mg/min) and Fa/- (1.64 +/- 0.63 mg/min) groups but not between Fa/- and fa/fa (1.29 +/- 0.61 mg/min) groups, indicating a strain effect in organic anionic renal transport. The Fa/- vs fa/fa comparisons were significant when GFR, ERPF and Tm were corrected for total body or kidney weight. In a second group of animals (study 2), GFR (as reflected by creatinine clearance [Clcr]) and histologic studies were performed in Fa/- and fa/fa rats. Clcr values were significantly higher in the fa/fa (2.10 +/- 0.44 ml/min) vs Fa/- (1.68 +/- 0.17 ml/min). Histologic studies in group 2 demonstrated no remarkable differences between Fa/- and fa/fa rats. These results suggest wide interanimal variation in obesity associated changes in renal function and possibly pathology in the fa/fa rat.

Animals↗
PubMed1985

Ultrasound measures of vitreous chamber depth during ocular accommodation.

The vitreous chamber decreased in depth about 0.12 mm as accommodative demand increased from 0.2 to 7 D in nine accommodative steps. The depth decreases matched movement of the posterior lens surface toward the retina. Accommodation caused no significant increases in axial length compared to cyclopleged controls. These results do not favor the active role for the vitreous in accommodation proposed by Coleman in 1970. Computer analysis of A-scan interval counts demonstrated that multiple retinal complex peaks might erroneously point to vitreous or axial lengthening. About 30% of total lens thickening during accommodation was accounted for by posterior lens surface displacement.

Accommodation, Ocular↗
PubMed1983

Joint complaints and food allergic disorders.

An important problem in investigating food allergic diseases is to adduce evidence that specific diseases of unknown cause may be attributable to food allergy. Polyarthritis is a good example of the difficulties involved in such studies because it is a very heterogeneous disorder and generalizations about aetiology are unlikely to prove correct. We have observed transient synovitis in both children and adults which is caused by food allergy. On the other hand we have not been able to show that food allergy demonstrably contributes to juvenile chronic arthritis or to rheumatoid arthritis in adults. The arthritis associated with inflammatory bowel disease undoubtedly responds to elemental diets and the mechanism of this remission warrants further investigation.

Arthritis, Rheumatoid↗