Biomedical subjects

R A Jackson

Publications and source records attributed to R A Jackson.

At least 73 records · Page 4Linked to original sources

PubMed1987

An ultrastructural examination of murine alveolar macrophages following intranasal administration of propionibacterium acnes.

Light and electron microscopic analysis of murine lungs or isolated pulmonary cells was performed three days after intranasal administration of the bacterial immunostimulant, Propionibacterium acnes (P. acnes). Our observations indicated that pulmonary alveolar and airway macrophages (PAMs) were the only cells with P. acnes bacilli in their cytoplasm. Bacilli were not observed in pulmonary interstitial macrophages, granulocytes, lymphocytes or pulmonary parenchymal cells such as type I and type II pneumocytes. Because of the morphological heterogeneity of PAMs observed in control and experimental animals, it was not possible from these studies to be certain about the relative abundance or complexity of lysosomes, endoplasmic reticulum, Golgi and other organelles in the two groups. However, we noted that it was not uncommon to observe in the same PAM, profiles of P. acnes and a well developed Golgi complex and endoplasmic reticulum. These P. acnes--associated morphological alterations occurred at a time when functional activities (e.g., phagocytosis, cytostasis) of PAMs were enhanced.

Animals↗

PubMed1986

The NOD mouse: recessive diabetogenic gene in the major histocompatibility complex.

Examination of the histocompatibility region of the nonobese diabetic (NOD) mouse with antibodies against class II glycoproteins (products of immune response genes of the major histocompatibility complex I-A and I-E), hybrid T-cell clones, and mixed-lymphocyte cultures and analysis of restriction fragment length polymorphisms indicate that the NOD mouse has a unique class II major histocompatibility complex with no expression of surface I-E, no messenger RNA for I-E alpha, and an I-A not recognized by any monoclonal antibodies or hybrid T-cell clones studied. In crosses of NOD mice with control C3H mice, the development of diabetes was dependent on homozygosity for the NOD mouse's unique major histocompatibility region.

Animals↗

PubMed1986

Role of pulmonary macrophages in resistance to experimental metastasis.

Intranasal inoculation of C3H/HeN mice with Propionibacterium acnes activates pulmonary macrophages but not splenic or peritoneal macrophages. When mice so treated were injected IV with tumor cells, no protection against the challenge was seen. Conversely, inoculation of C3H/HeN mice with P. acnes by the IP route activated splenic and peritoneal macrophages but not pulmonary macrophages. When mice with activated splenic and peritoneal macrophages were challenged with an IV injection of tumor cells, the mice demonstrated an increased resistance to the formation of pulmonary tumors. Thus, activation of splenic and peritoneal macrophages correlated better with protection against IV tumor challenge than activation of pulmonary macrophages. Experiments were done that demonstrated that the effect was not due to the augmentation of NK cell activity. The data are consistent with the conclusion that activated pulmonary macrophages alone are not effective in conferring resistance to pulmonary tumor nodule formation in this tumor model.

Animals↗

PubMed1986

Amiodarone therapy and autoimmune thyroid disease. Increase in a new monoclonal antibody-defined T cell subset.

T cell subsets in 10 patients receiving amiodarone were evaluated, and their thyroid function and antithyroid antibodies were assessed. A generalized increase in a recently discovered subset of T cells expressing a complex ganglioside antigen reacting with monoclonal antibody 3G5 was found. Two patients, one with hyperthyroidism and the other with euthyroid Graves' ophthalmopathy, had an additional T cell abnormality--marked increase in Ia-positive T cells (an abnormality typical of patients with spontaneous Graves' disease). In the hyperthyroid patient, the Ia-positive T cells disappeared within three weeks after amiodarone was discontinued. The other patients receiving amiodarone had normal numbers of Ia-positive T cells. These studies indicate that amiodarone alters a major resting T cell subset for almost all patients and is associated with T cells expressing the Ia antigen in selected patients. These T cell abnormalities suggest that amiodarone precipitates organ-specific autoimmunity in susceptible persons.

Adult↗

PubMed1986

The availability of ovine infective trichostrongyle larvae on forested paddocks.

A study was made to compare the numbers of infective ovine nematode parasite larvae on an open pastured block and an adjacent block forested with Pinus radiata at 200 stems per hectare. Each block consisted of two paddocks which had similar nematode parasite egg contamination. Infective larvae of six genera were recovered over a 12 month period viz., Trichostrongylus spp., Ostertagia spp., Cooperia spp., Nematodirus spp., Chabertia/Oesophagostomum spp. and Haemonchus sp. A significantly higher recovery of Trichostrongylus spp. (p<0.01) and Ostertagia spp. (p<0.05) from the pine forested block was probably due to the more favourable climatic environment under the pines. The lower mean body weights of sheep grazing the pine block was considered to be due to the greater exposure to infective larvae and marginal under-nutrition.

Journal Article↗

PubMed1986

Impact of glucose ingestion on hepatic and peripheral glucose metabolism in man: an analysis based on simultaneous use of the forearm and double isotope techniques.

The metabolic response to glucose ingestion was studied in 10 normal men (aged 21-23 yr) by the simultaneous application of the forearm and double isotope techniques. The latter consisted of a primed constant infusion of [3-3H]glucose, followed by the administration of an oral glucose load (mean +/- SE, 90.7 +/- 0.7 g) containing [1-14C]glucose. Most (80.6 +/- 8.1%) of the ingested glucose appeared systemically within 270 min, suggesting that initial splanchnic glucose extraction accounted for 19.4 +/- 3.1% (17.7 +/- 2.8 g) of the oral load. Basal hepatic glucose output (2.22 +/- 0.12 mg/kg X min) was reduced (P less than 0.005) within 30 min after glucose loading and remained suppressed throughout the study; its mean reduction from 0-270 min was 54.9 +/- 9.9%, thereby accounting for the conservation of 26.5 +/- 4.9 g glucose. Suprabasal glucose appearance from 0-270 min was 46.6 +/- 4.3 g. Forearm glucose uptake rose 8.5-fold to 0.664 +/- 0.083 mg/100 ml forearm X min at 45 min, but basal forearm oxygen uptake (6.1 +/- 0.4 mumol/100 ml forearm X min) did not change. The increment in glucose disappearance from 0-270 min was 46.4 +/- 3.8 g, of which increased glucose uptake by muscle, determined from the forearm glucose uptake data, accounted for 37.7 +/- 5.1 g (81%). If uptake of the remaining 8.7 g was shared equally by the liver and peripheral tissues, the splanchnic bed and periphery would account, respectively, for 47.1 g (52%) and 43.5 g (48%) of the ingested load. We conclude that splanchnic and peripheral tissues contribute almost equally to the total homeostatic response; in kinetic terms, decreased hepatic glucose output and increased glucose uptake (splanchnic plus peripheral) constitute 29% and 71% of the total response, respectively; restoration of basal glucose kinetics after glucose ingestion requires more than 270 min; and increased peripheral oxygen uptake is not the mechanism of glucose-induced thermogenesis which, instead, may reflect increased splanchnic oxygen consumption.

Administration, Oral↗

PubMed1986

The influence of graded hyperglycemia with and without physiological hyperinsulinemia on forearm glucose uptake and other metabolic responses in man.

We studied the influence of hyperglycemia on glucose homeostasis in man by determining the effect of graded hyperglycemia on peripheral glucose uptake and systemic metabolism in the presence of basal and increased serum insulin concentrations in 10 normal men. This was achieved by the simultaneous application of forearm and clamp techniques (euglycemic and hyperglycemic) during the combined iv infusion of somatostatin, glucagon, and insulin. While mean (+/- SE) basal serum insulin levels (14 +/- 2 microU/ml) were maintained, the elevation of fasting arterial glucose concentrations (90 +/- 1 mg/dl) to 146 +/- 1 and 202 +/- 1 mg/dl (each for 120 min) increased forearm glucose uptake (FGU) only modestly from 0.06 +/- 0.01 to 0.15 +/- 0.02 and then to 0.24 +/- 0.03 mg/100 ml forearm X min, respectively. During physiological hyperinsulinemia (47 +/- 3 microU/ml), the influence of similar graded hyperglycemia on FGU was considerably enhanced. At plasma glucose concentrations of 90 +/- 1, 139 +/- 1, and 206 +/- 1 mg/dl, FGU rose to 0.33 +/- 0.05, 0.59 +/- 0.07, and 0.83 +/- 0.12 mg/100 ml forearm X min, respectively. The glucose infusion rate required to maintain the glucose clamp with basal insulin levels was 1.08 +/- 0.20 and 2.67 +/- 0.39 mg/kg X min at glucose concentrations of 146 +/- 1 and 202 +/- 1 mg/dl, respectively. During physiological hyperinsulinemia, however, the glucose infusion rate required was 4.15 +/- 0.39, 9.45 +/- 1.05, and 12.70 +/- 0.81 mg/kg X min at glucose levels of 90 +/- 1, 139 +/- 1, and 206 +/- 1 mg/dl, respectively. Lactate concentrations rose significantly during hyperglycemia, but the rise in the presence of increased insulin concentrations (from 0.72 +/- 0.06 to 1.31 +/- 0.11 mmol/liter; P less than 0.001) considerably exceeded the increment (from 0.74 +/- 0.05 to 0.92 +/- 0.03 mmol/liter) with basal insulin levels. While both FFA and glycerol concentrations were immediately reduced by euglycemic hyperinsulinemia, the fall in FFA during hyperglycemia in the presence of basal insulin levels preceded the decrease in glycerol concentrations by 45 min. Forearm oxygen consumption did not change throughout the study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1986

Adjuvant chemotherapy of axillary node-negative carcinoma of the breast using doxorubicin and cyclophosphamide.

One hundred fifty-six women with axillary node-negative breast cancer and primary tumors less than or equal to 5 cm in diameter (T1N0 or T2N0) were treated with a brief course of postoperative adjuvant chemotherapy consisting of doxorubicin and cyclophosphamide. Treatment was well tolerated and toxicity was minimal. With a median follow-up time of 58 months, there has been 1 relapse among 58 patients with T1 primary lesions and 15 relapses among 98 patients with T2 primary tumors. When compared with a matched historical control group receiving surgery alone, significant improvement was apparent in disease-free survival among the patients who received adjuvant chemotherapy. Prospective controlled trials are needed if we are to confirm this favorable experience with adjuvant chemotherapy in the treatment of women with node-negative breast cancer.

Adult↗

PubMed1986

Burnout experienced by recent pharmacy graduates of Mercer University.

The degree of burnout experienced by graduates of the Mercer University Southern School of Pharmacy from 1973 to 1983 was studied. Questionnaires were mailed to 1000 alumni, representing 850 Bachelor of Science (B.S.) and 150 Doctor of Pharmacy (Pharm.D.) graduates. Three components of burnout--emotional exhaustion, depersonalization, and personal achievement--were measured using the Maslach Burnout Inventory to determine relationships between burnout and primary work setting, primary work activity, and type of degree (Pharm.D. or B.S.). The response rate was 41%. The respondents experienced a moderate degree of burnout. Those pharmacists working primarily in community chain store settings reported greater levels of burnout than those working in hospital or institutional pharmacies, independent community pharmacies, academia, and home health care. Respondents who performed primarily nondistributive duties (direct patient care, drug information, teaching or research, and management or administration) experienced lower levels of burnout than those involved primarily in drug distribution. Pharmacists holding the Pharm.D. degree were involved to a greater extent in nondistributive positions and experienced a lower degree of burnout than the pharmacists holding a B.S. degree only. Pharmacists in nondistributive roles appear to be less affected by burnout than pharmacists performing traditional distributive activities.

Burnout, Professional↗

PubMed1985

Major histocompatibility complex restriction fragment length polymorphisms define three diabetogenic haplotypes in BB and BBN rats.

Class I and II major histocompatibility complex (MHC) probes can be used to subdivide diabetes-prone BB rats and their BBN control strain, coderived from the same outbred colony by selection against diabetes. Class II probes (A-alpha in particular) distinguish four restriction fragment length polymorphisms (RFLP), termed 1a, 1b, 2a, and 2b, in the BBN population, only one of which (2a) is found in BB rats. The degree of class II RFLP in the population studied is RT1.B-alpha greater than or equal to RT1.B-beta greater than RT1.D-alpha greater than or equal to RT1.D-beta, suggesting that intra-class II region dynamics may be different in rats compared with mice. A class I probe (S16) absolutely distinguished BB from BBN rats, since all BB rats exhibit an RFLP pattern termed 2a0, while 2a BBN rats can be subdivided into 2a1 and 2a2 forms. Serologic evaluation has shown that 2a0, 2a1, and 2a2 rats express RT1.AuBu, 1a rats express RT1.AaDa, and 1b rats express neither RT1a nor RT1u at the loci tested. A breeding study was carried out to determine the diabetogenicity of the MHC-defined RFLP's. As expected, the BB-derived 2a0 is diabetogenic. The BBN-derived 2a1 and 2a2 RFLPs are also diabetogenic, while 1a and 1b rats do not carry MHC-linked diabetogenic genes. The MHC-linked diabetes gene acts in a functionally recessive manner, since there is a 10-fold higher incidence in homozygotes than in heterozygotes. Analysis of the RFLP patterns leads us to hypothesize that the 2a1 RFLP results from a crossover between 1a and 2a0 MHCs and that the diabetogenic MHC-linked gene is on the class II side of Qa and T1. The availability of three diabetogenic MHC haplotypes should help localize the MHC-linked diabetogenic gene of rats.

Animals↗

PubMed1985

Noise exposure--sample size and confidence limit calculation.

In a previous paper a method for assessing noise exposure levels of workers from the same trade was presented. There was also discussed how to apply the NIOSH sample size method to noise exposed populations. In this paper both subjects are further discussed by including the calculation of confidence limits for the mean noise exposure as well as for the percentage of workers with noise exposure levels beyond a certain level. The calculation of the sample size of a population where standard deviation is known is also discussed.

Environmental Exposure↗

PubMed1985

Low expression of human histocompatibility leukocyte antigen-DR is associated with hypermethylation of human histocompatibility leukocyte antigen-DR alpha gene regions in B cells from patients with systemic lupus erythematosus.

The relationship between the expression of HLA-DR antigens and the HLA-DR alpha gene methylation was examined in systemic lupus erythematosus (SLE). Using permanent B cell lines, we found reduced DR expression in SLE. The low DR expression was correlated with high anti-DNA antibody titers in patients' sera. The amounts of DR alpha message were lower in SLE cells than in normal controls, suggesting that the low expression of DR antigens is associated with gene functions. The extent of DNA methylation was examined at five CCGG sites in the HLA-DR alpha locus. DNA from both SLE and normal cells showed variable methylation patterns. Since the DR alpha gene is a single-copy gene, such a variability is the result of assaying a mixture of transformed clones containing methylated DR alpha gene, with other clones containing unmethylated DR alpha gene. A distinctive feature of normal cells was a consistent methylation pattern: 12 normal cell lines showed exactly the same pattern. In contrast, 28 SLE cell lines showed a cell-line-specific methylation, and hypermethylation at the DR alpha locus. The hypermethylation is often associated with transcriptionally inactive genes. Thus, our results suggest that (a) B cells with hypermethylated DR genes might express no or few DR antigens; (b) the ratio of cells with differently methylated DR genes is consistent in normal individuals, while, in SLE patients, cells with hypermethylated DR genes predominate, resulting in apparently reduced DR antigen expression; and (c) the aberrant DR expression could be associated directly with immunoregulatory dysfunctions in SLE disease.

Antibodies, Antinuclear↗

PubMed1985

A comparison of a multi-media instructional module with a traditional lecture format for geriatric pharmacy training.

The purpose of this study was to develop, produce, and test the effectiveness of a multi-media instructional module versus a traditional lecture format. The subject selected was geriatric care in relation to pharmacy practice. A pretest/posttest control group design was used, differing only in the method of presentation of the material. The control group received four fifty-minute traditional lectures, and the treatment group utilized the module for the acquisition of the information. An evaluation of the pretest scores showed that the groups were equal in knowledge (no significant difference at P = 0.05) before exposure to the information. A comparison of the posttest scores of the two groups showed that the module was as effective a learning strategy as the traditional lectures (no significant difference at P = 0.05). The comparison of the pretest and posttest scores within each group showed that significant improvement occurred following the utilization of both methods of instruction at P less than 0.05. The results of this project indicated that the module is an effective learning strategy when compared to a traditional lecture format. It was also evident that the multi-media module can be used as an instructional alternative in the education of pharmacy students.

Analysis of Variance↗

PubMed1984

Two genes required for diabetes in BB rats. Evidence from cyclical intercrosses and backcrosses.

The BB rat develops a syndrome of autoimmune diabetes similar to Type I diabetes of man. It also has a severe T cell lymphopenia. As part of an ongoing breeding program to transfer the diabetogenic genes of the BB rat onto inbred rat strain backgrounds, diabetic animals were used in a backcross (BC)- intercross (IC)-backcross breeding scheme with Brown Norway (BN), Lewis (L), and Wistar-Furth (WF) inbred rats. We have used monoclonal antibodies to analyze both lymphopenia and major histocompatibility (MHC) antigens (the RT1 locus in the rat) in relation to the development of diabetes. To examine T cell subsets we used a panel of monoclonal antibodies, in particular W3/25 and OX19 , which discriminate the abnormal phenotype better than W3/13. In our breeding program, at least two independent genes or gene complexes are required for the expression of diabetes. One gene determines the lymphopenia, is inherited by simple autosomal recessive genetics and is not linked to the MHC. The second gene is linked to the MHC. Both genes are necessary, but neither gene is sufficient by itself for the development of diabetes.

Animals↗

PubMed1984

Class I, II and III major histocompatibility complex gene polymorphisms in BB rats.

The BB rat spontaneously develops insulin-dependent diabetes mellitus of autoimmune aetiology. From breeding studies, one of the genes necessary for the development of diabetes in these animals is linked to RT1, the rat's major histocompatibility complex. To study further the RT1 linked diabetogenic gene of the BB rat, we have studied restriction fragment length polymorphism using 32P-labelled DNA probes of the major histocompatibility complex genes. As we have previously reported, an I-A alpha probe (mouse class II gene) defines four chromosome types in the control BBN population, only one of which is found among diabetes prone BB rats. All BB rats we have studied are homozygous for the type IIa chromosome. Here we examine restriction fragment length polymorphisms using three other DNA probes. Using a DC beta-probe (human class II), the same pattern of polymorphisms (though different molecular weights) is found as with the I-A alpha probe. An H-2d C4 (fourth component of complement, mouse class III) defines no polymorphisms among or between BB and BBN rats. Using H-2 LdC-2 domain probe (mouse class I) many polymorphisms are apparent and in a limited series distinguishes I-A alpha defined IIa/IIa BBN rats from IIa/IIa BB rats. These studies provide the basis to subtype the RT1u identical BB and BBN animals and should aid in the localization and characterization of the RT1 linked diabetogenic gene of the BB rat.

Animals↗

PubMed1984

Pre-type 1 (insulin-dependent) diabetes: common endocrinological course despite immunological and immunogenetic heterogeneity.

In an ongoing prospective study 32 individuals have been evaluated for insulin secretory dynamics, islet cell antibodies and HLA antigens, during the preclinical phase of Type 1 diabetes mellitus. Twenty-four out of the 32 subjects were islet cell antibody-positive. To date, 14 subjects (10 islet cell antibody-positive, four islet cell antibody-negative) have progressed to develop overt diabetes. Several patterns of HLA-DR expression were noted (DR3/DR4, DR3/DR3, DR3/x, DR3/DR1, DR4/x, DR4/DR7, DR5/DR7, DR1/DR7 and DR1/DR2). Irrespective of differences in islet cell antibody status or HLA-DR alleles, pre-diabetic individuals exhibited a similar slow course of progressive beta-cell dysfunction.

Adolescent↗

PubMed1984

Ia-positive T lymphocytes in recently diagnosed idiopathic Addison's disease.

The Ia (DR, immune-associated) antigen is absent on normal circulating T lymphocytes, but present on activated T lymphocytes. Utilizing monoclonal antibody L243, the expression of this glycoprotein on circulating T lymphocytes was studied in five patients with recent-onset idiopathic Addison's disease, one patient with recent-onset adrenal hemorrhage, and nine patients with long-standing adrenal insufficiency (five with idiopathic Addison's disease and four after bilateral adrenalectomy for Cushing's disease). The patient with adrenal hemorrhage and the nine patients with long-standing adrenal insufficiency had percentages of circulating Ia-positive T cells within the normal range. All five patients with recent-onset idiopathic Addison's disease had an elevated percentage of circulating Ia-positive T cells (7 to 29 percent). The expression of Ia antigen on T cells in recent-onset idiopathic Addison's disease probably reflects immunologic activation, which may be of pathophysiologic importance.

Addison Disease↗

PubMed1984

Analysis of the insulin receptor by anti-receptor antibodies and flow cytometry.

We characterized insulin receptors on a human lymphoblastoid cell line (IM-9) and studied their regulation using anti-receptor antibodies and fluorescence flow cytometry. The fluorescence intensity distribution of insulin receptors on cells was determined by incubating the cells with one of three different anti-receptor antisera (human serum B-9 containing polyclonal autoantibodies, serum from a rabbit with polyclonal antibodies, and a monoclonal antibody to the receptor produced in mouse hybridomas), followed by incubation with an appropriate fluorescein isothiocyanate-labeled second antibody and analysis on an Epics-V flow cytometer. All three anti-receptor antibodies specifically labeled the insulin receptors. The monoclonal antibody showed the highest level of labeling. Treatment of cells with proteolytic enzymes, such as trypsin or chymotrypsin, produced a dose-dependent loss of 125I-labeled insulin (125I-insulin) binding but a relatively small decrease in the binding of anti-receptor antibodies, suggesting that most antibody binding occurred in domains other than the insulin binding site. Treatment with glycosidic enzymes, such as neuraminidase and beta-galactosidase did not affect the binding of 125I-insulin, and fluorescence was actually enhanced by about 20% in the beta-galactosidase-treated cells. Exposure of IM-9 cells to insulin resulted in a reduction in the number of insulin receptors. Analysis of the down-regulated cells by immunofluorescence revealed a complete correlation between the percent binding of 125I-insulin and percent peak fluorescence. In all cases, receptors were lost proportionally from all cells, yielding a single symmetrical peak by fluorescence analysis. Exposure of IM-9 cells to anti-receptor antibodies at 37 degrees C for 16 hr also produced a down-regulation in the number of insulin receptors. Incubation with human antiserum B-9 caused a 95% loss of both 125I-insulin binding and peak fluorescence, while the monoclonal antibody resulted in a 50% loss of receptors. Incubation of cells with anti-receptor antibodies for 2 hr at 4 degrees C did not produce any receptor loss; however, the human anti-receptor antisera B-2 and B-9 inhibited the binding of the monoclonal anti-receptor antibody by about 50%, suggesting that these antisera contained autoantibodies directed at the monoclonal antibody binding site. These data indicate that insulin receptors can be regulated by both insulin and anti-receptor antibody and demonstrate the utility of immunofluorescence and flow cytometry as a tool for the study of the insulin receptor.

Antibodies, Monoclonal↗