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Biomedical subjects

R A Jackson

Publications and source records attributed to R A Jackson.

At least 91 records · Page 5Linked to original sources

Ia+ T cells in new onset Graves' disease.

The Ia (immune-associated, DR) antigen is a cell surface glycoprotein which is absent on normal circulating T lymphocytes but present on activated T lymphocytes. We studied the expression of this antigen on circulating T lymphocytes from patients with untreated hyperthyroid Graves' disease. All patients (n = 33) with recent onset hyperthyroid Graves' disease studied had an increased percentage and number of circulating Ia+ T cells. Patients with non-Graves's hyperthyroidism or Graves' disease patients more than 1 yr after thyroid ablation had normal values for Ia+ T cells. Other cell surface activation antigens, recognized by monoclonal antibodies 4F2 and 5E9, were not present on circulating T cells in patients with Graves' disease. The 100% positivity for increased numbers of Ia antigen-bearing T cells in hyperthyroid Graves' disease contrasts with our finding of 70% positivity in another HLA-DR-associated disease, recent onset type I diabetes mellitus. The pathogenic significance of these cells is not known, but they seem to represent selective activation of the immune system in patients with untreated hyperthyroid Graves' disease.

Adolescent↗

Relationship among peripheral glucose uptake, oxygen consumption, and glucose turnover in postabsorptive man.

To assess the importance of glucose uptake by muscle in determining total glucose utilization in the basal state, forearm glucose uptake (FGU), reflecting mainly skeletal muscle metabolism, and glucose turnover using [3-3H]glucose were studied simultaneously in 17 postabsorptive normal men. Mean +/- SE glucose disappearance was 2.36 +/- 0.14 mg/kg X min, amounting to 170 +/- 9 mg/min, while FGU was 0.049 +/- 0.009 mg/100 ml forearm X min. When the latter was calculated in terms of skeletal muscle in the body as a whole, muscle glucose utilization was found to be 24.7 +/- 4.5 mg/min, comprising only 13.5 +/- 1.9% of the total glucose disappearance. Forearm oxygen consumption was 6.6 +/- 0.5 mumol/100 ml forearm X min, of which only 26 +/- 5% could be accounted for by concurrent glucose uptake. These results suggest that in the basal state, glucose uptake by skeletal muscle accounts for 1) only a small percentage of total glucose disappearance and 2) only a minor proportion of peripheral oxygen consumption, which may be more dependent on lipid oxidation.

Adult↗

Specific class II histocompatibility gene polymorphism in BB rats.

The BB rat spontaneously develops insulin-dependent diabetes mellitus of autoimmune etiology. From breeding studies, one of the genes necessary for the development of diabetes in these animals is linked to RT1, the rat major histocompatibility complex. To better define the BB rat's RT1-linked diabetogenic gene (RT1-DM), we have used restriction endonucleases BamH1 and EcoR1 in conjunction with an I-A alpha (class II mouse major histocompatibility complex) gene probe to study RT1 class II gene polymorphisms among diabetes-prone BB rats and the related non-diabetes-prone BBN rats. Both BB and BBN rats are indistinguishable RT1u by serologic methods. Four polymorphic chromosome types (la, lb, lla, and llb) were recognized among the control BBN rats. In contrast, all BB rats were homozygous (lla/lla). From the multiple breeding programs involved, we hypothesize that the BB rat's RT1-linked diabetogenic gene is linked to an l-A alpha-defined gene of the type lla chromosome. The ability to split the RT1u of BB rats will provide a powerful tool to localize and characterize RT1-DM.

Animals↗

Pre-type I diabetes. Linear loss of beta cell response to intravenous glucose.

Twenty-one intravenous (i.v.) glucose tolerance tests were performed on nine subjects before the onset of overt type I diabetes mellitus. Islet cell antibodies (6 of 9 subjects) and elevated levels of Ia-positive T-lymphocytes (3 of 3 subjects studied) were detected during the prediabetic period. Elevations of fasting blood glucose and peak glucose during oral glucose tolerance tests were not observed until the year before onset of clinically overt diabetes. During the prediabetic period, there was a progressive loss of early-phase insulin release to i.v. glucose (rate of decline, 20-40 microU/ml insulin release/yr; correlation coefficient, 0.9).

Administration, Oral↗

Multiagent chemotherapy in relapsing ovarian cancer.

A multiagent regimen (vinblastine, bleomycin, hexamethylmelamine, and cis-platinum) partly designed on the basis of data from a human tumor stem cell assay was used to treat 36 patients with relapsing epithelial ovarian cancer. All patients included in this study had previously received alkylating agent therapy, and 78% (28/36) had also received Adriamycin. Thirty-five patients were clinically evaluable for response; eight achieved complete clinical remission, and nine achieved partial remission, for an overall response rate of 49%. The median duration of response was 10 months, and three of the complete responders are in remission at 10+, 17+, and 22+ months. Mild to moderate peripheral neuropathy was the major side effect, occurring in 11% (4/35) of patients. Myelotoxicity was well tolerated. We conclude that this four-drug regimen is effective in the treatment of relapsing ovarian cancer patients and should be considered for study as a front-line combination chemotherapy for previously untreated patients.

Altretamine↗

Comparison of peripheral glucose uptake after oral glucose loading and a mixed meal.

Forearm glucose uptake (FGU) and other metabolic responses were studied in six normal men for three hours after a 75-g oral glucose load and a mixed meal containing 75 g carbohydrate. After the meal the rise in arterial glucose levels was considerably less than that following the oral glucose load but the overall insulin responses from 0 to 180 minutes were not statistically different. Although the initial rise in FGU was more gradual after the meal, the subsequent elevation was more sustained and, at the termination of the study, exceeded significantly that seen after the oral glucose load. The rise in GIP levels during the first hour was similar after the meal and the oral glucose load, but thereafter concentrations following the oral glucose load fell while those after the meal continued to rise. When the incremental area (delta) is used as the index of response, the results show that while the glucose response (delta G) after the meal (19.1 +/- 5.3 units) was only 26% of that after oral glucose loading (72.7 +/- 7.0 units), the corresponding increase in FGU (delta FGU) reached 62% (55.0 +/- 12.8 units after the meal, 89.2 +/- 20.0 units after the oral glucose load). Thus, the increase in peripheral glucose uptake relative to the glycemic response (delta FGU/delta G) was significantly greater after the meal than following the oral glucose load alone (P less than 0.05). In conclusion, relative to the rise in arterial glucose levels, peripheral glucose uptake is greater after a meal than after glucose loading with an equivalent carbohydrate challenge. Furthermore, the present data support previous studies emphasizing the failure of GIP alone to explain the entero insular axis.

Administration, Oral↗

Peripheral glucose uptake in young men with myocardial infarction.

Forearm glucose uptake (FGU) was studied during 100 g oral glucose tolerance tests (GTT) in nonobese, nondiabetic men who had suffered a myocardial infarction (MI) at or before the age of 40, and the results compared with the response in age-matched normal men. In the MI group the rise in both glucose and insulin concentrations after glucose loading was similar to that in normal subjects, although in the former, peak levels tended to be slightly higher. Concomitant FGU, however, was significantly greater in the MI group than in control subjects in the period 0-90 min and in the test as a whole (0-180 min). The results show that at least in some nondiabetics suffering MI at an early age hyperinsulinism is not a feature and peripheral tissue sensitivity is increased.

Adult↗

Enhancement of natural resistance to influenza virus in lipopolysaccharide-responsive and -nonresponsive mice by Propionibacterium acnes.

Lipopolysaccharide-responsive C3H/HeN mice were rendered resistant to a mouse-adapted strain of influenza (Aichi, H(3)N(2)) virus when Propionibacterium acnes was given either intranasally or intraperitoneally several days before virus infection. The time of P. acnes treatment was important since no protection was demonstrated when this agent was given either on the same day as or several days after virus challenge. In contrast, lipopolysaccharide-nonresponsive C3H/HeJ mice were not protected when P. acnes was administered intranasally at any time before infection; however, protection was demonstrated when P. acnes was given by the intraperitoneal route. Depending on the route of inoculation, P. acnes induced several distinctive immunological responses in the lungs of both C3H/HeN and C3H/HeJ mice. Intranasal inoculation was more effective in activating pulmonary macrophages in C3H/HeN than in C3H/HeJ mice. In contrast, intraperitoneal inoculation activated pulmonary natural killer cells in both mouse lines but did not activate pulmonary macrophages.

Adjuvants, Immunologic↗

Type I diabetes mellitus in monozygotic twins: chronic progressive beta cell dysfunction.

In a prospective 21-year study, islet cell antibodies and beta cell function were serially assessed in 24 monozygotic twins initially discordant for type I diabetes mellitus. Eighteen of 21 twins typed had HLA-DR3 or HLA-DR4 antigens. During the follow-up, 4 twins developed type I diabetes mellitus, and in 3 of these 4 twins islet cell antibodies preceded the diagnosis of clinical diabetes mellitus by greater than 8, 5 and 7 years respectively. During the "prediabetic phase," the presence of islet cell antibodies was temporally associated with a progressive decline in first phase insulin response to intravenous glucose. Elevations in fasting blood glucose and abnormalities on oral glucose tolerance tests appeared only later during the course of the disease. Of the remaining 20 twins who continue to be discordant for type I diabetes mellitus, two have had islet cell antibodies for greater than 1.5 and 1 year respectively. One of these islet cell antibody-positive non-diabetic twins was restudied; despite a fasting blood glucose level of 64 mg/dL, she had a total absence of first phase insulin response to intravenous glucose. There was no evidence of transient islet cell antibody positivity in any of the twins studied. Type I diabetes mellitus in monozygotic twins has a prolonged prediabetic phase of progressive beta cell dysfunction with associated immunologic abnormalities.

Antibodies↗

Type I diabetes of man and the BB rat: monoclonal antibody-defined T-cell abnormalities.

Both patients and BB rats with type I diabetes mellitus have demonstrated major T-cell abnormalities, the appearance of which precede the development of overt hyperglycemia. The BB rat experiences a profound T lymphocytopenia which appears to be a necessary antecedent but is not totally sufficient in itself for the development of diabetes. Meanwhile, patients exhibit an elevated percentage of circulating T cells bearing the Ia or Dr antigen. Daily prednisone administration selectively decreases Ia+ T cells, and antithymocyte globulin (ATGAM) plus prednisone has a long-lasting effect in suppressing OKT4+ T cells in patients with recent-onset type I diabetes.

Animals↗

Continuing changes in the contour of the maxillary residual alveolar ridge.

Using a cast measuring technique, the change in contour of the residual maxillary alveolar ridge of patients who have worn dentures for a number of years and are then fitted with new dentures, has been investigated. The study confirmed that even after 30 years of denture wearing, further bone resorption may occur beneath new dentures.

Aged↗

Interpretation of research data: selected statistical procedures.

Selected statistical procedures used in the analysis of research data are presented. The relationship of significance testing to research hypotheses is explained in terms of tests of differences and correlation. Also, the differences, assumptions, and advantages and disadvantages of parametric and nonparametric statistics are discussed. With regard to each statistic presented, emphasis is placed on the hypotheses that would be tested, the kinds of data for which the statistic is appropriate, the method of calculation, and how to test for "significance." The selected statistical procedures include the Student's t-test and chi square. An explanation of the concept of correlation is provided, and several correlation coefficients are discussed, including the Pearson r, Spearman rho, Kendall's tau, the point biserial, biserial, phi coefficient, and contingency coefficient. Pharmacists must know basic statistical procedures in order to be able to effectively interpret the results of published research or to appropriately analyze data that have been collected in their own research endeavors.

Methods↗

The effect of yttrium-90 implantation on endocrine function and visual fields in patients with "functionless" pituitary tumors, with biopsy and radiological findings.

Thirty patients with symptoms from "functionless" pituitary tumours were treated by yttrium-90 implants, and we report here the effects on symptoms, pituitary function and visual fields. On biopsy, about a third of the tumours showed some hormone granules. In the sixteen fully assessed at 1 year, pituitary function was improved in 25%, unchanged in 62-5%, and reduced in 12-5%. Improvement was confined to those in whom gonadotrophin secretion was the only function impaired pre-implant. Visual field defects were present pre-implant in ten patients (twenty eyes); at 1 year post-implant these defects had lessened in 80% and deteriorated in only 5% of eyes. Subsequently, within 5 years of the implant the field defects had worsened or recurred in four patients, all with initially extensive suprasellar projection; further treatment was then given. Remineralization of the sella was seen after implantation in seven cases, with reduction in fossa size in five. Thus pituitary implantation appears to be a practicable and reasonably simple procedure suitable for the treatment of most cases of "functionless" pituitary tumour. The "supressive" doses of irradiation used are adequate to shrink most tumours without loss of pituitary function.

Adenoma↗