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Biomedical subjects

S K Anderson

Publications and source records attributed to S K Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1993

Relationship of pain behavior to disease activity and health status in rheumatoid arthritis.

The purpose of the study was to investigate the contributions of disease activity, health status, and self-efficacy to the pain behavior exhibited by patients with rheumatoid arthritis. Measures included the Arthritis Impact Measurement Scales, the Arthritis Self-Efficacy Scale, a visual analogue scale for pain, and the McGill Pain Questionnaire. Joint counts and ratings of pain behavior also were obtained. All measures were collected at both baseline and 6 months. Hierarchical multiple regression analyses revealed that disease activity, as measured by joint count, was significantly related to a modified pain behavior index at both time intervals. With joint count entered into the regression model, no other variable consistently increased the predictive accuracy of the model. There were no significant correlations between the modified pain behavior index and either the visual analogue scale for pain or the McGill Pain Questionnaire scores. The results suggest that pain behavior in male rheumatoid arthritis patients is more closely related to disease activity than to self-reported pain, health status, or perceived self-efficacy.

Adaptation, Psychological↗
PubMed1993

IL-2 regulates the expression of the NK-TR gene via an alternate RNA splicing mechanism.

We have recently isolated and characterized human and mouse genes of a putative natural killer (NK) cell tumour-recognition protein (NK-TR) that is specifically expressed in NK cells. This gene codes for a 150 kD protein with a cyclophilin-related amino terminus followed by several positively charged domains. We report here the discovery of two sites of alternate splicing in the 5' region of the NK-TR mRNA. One of these events caused a frameshift in the open reading frame by splicing in a 28 bp exon within the cyclophilin coding region, resulting in the premature termination of the NK-TR protein. The second alternate splice stemmed from the use of an internal splice acceptor within an exon, producing a deletion of 25 amino acids in the NK-TR protein. The activation of NK cells by IL-2 produced a change in the splicing pattern that resulted in increased production of mRNAs capable of producing the complete NK-TR protein.

Alternative Splicing↗
PubMed1993

Glycemic control and development of retinopathy in youth-onset insulin-dependent diabetes mellitus. Results of a 12-year longitudinal study.

BACKGROUND: In 1979, the authors began a prospective study of the natural history of retinopathy in youth-onset insulin-dependent diabetes mellitus (IDDM). Their major goal was to determine if there was an association between glycemic control and the development and progression of retinopathy. METHODS: The study consisted of 420 individuals with IDDM (onset younger than 20 years of age) and no retinopathy at baseline. Study subjects were enrolled between 1979 and 1988. Stereo color fundus photographs were obtained annually. Two eye endpoints were recorded: duration when retinopathy was first detected, and when proliferative retinopathy was detected. Glycemic control was assessed by quarterly determinations of glycohemoglobin (GHb). Life-table analyses were performed relating duration of diabetes, sex, GHb, and age of diabetes onset to development of retinopathy. RESULTS: Retinopathy did not develop before 2 years' duration or before puberty. The prevalence of retinopathy was 50% by 9 years' duration and 100% by 20 years' duration. Retinopathy developed in females approximately 2 years sooner than in males, but plotting duration as postpubertal years resulted in nearly identical rates. Retinopathy developed significantly earlier in subjects with prepubertal onset of diabetes than in subjects with postpubertal onset if duration was plotted as postpubertal years. When separated into three groups based on GHb levels (< 7.5%, 7.5%-9%, > 9%), retinopathy developed approximately 2 years later in subjects in the less than 7.5% GHb group than those in the higher GHb groups. Proliferative retinopathy developed in 11 subjects. Their mean GHb level was higher than the mean GHb for those without proliferative retinopathy (10.9 versus 8.6%; P < 0.01). The higher the level of GHb, the sooner proliferative changes were detected. CONCLUSION: Long-term glycemic control is significantly related to both development and progression of retinopathy. Prepubertal duration of diabetes is a significant risk factor for the development of retinopathy.

Adolescent↗
PubMed1993

Cardiovascular responses in black and white males during exercise.

Previous investigations have shown blacks to have a significantly lower resting heart rate (HR) compared with whites. Our purpose was to determine if this difference exists during submaximal exercise and to compare other cardiovascular responses during submaximal exercise in black and white males. Sixteen black and 16 white males matched on age, body surface area, and maximal O2 consumption exercised at 0, 50, and 100 W on a cycle ergometer. HR, O2 consumption, and cardiac output via CO2 rebreathing were measured at rest and at each work rate. Stroke volume was then calculated. O2 consumption was not significantly different between blacks and whites at rest or at work rates of 0, 50, or 100 W. Cardiac output increased from rest with 0, 50, and 100 W work for both blacks and whites (6.1 to 13.0, 14.4, and 16.9 l/min and 5.7 to 12.2, 14.3, and 16.3 l/min, respectively). The differences in cardiac output between blacks and whites at rest and all work rates were not statistically significant. At rest and work rates of 0, 50, and 100 W, HR was significantly lower in blacks compared with whites (71, 99, 108, and 119 beats/min vs. 80, 107, 114, and 127 beats/min, respectively). The lower HR in blacks compared with whites was accompanied by a trend toward a higher stroke volume at rest and work rates of 0, 50, and 100 W (85.2, 130.3, 134.7, and 142.9 ml vs. 72.5, 114.9, 126.4, and 127.4 ml, respectively). No differences in resting blood pressures were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Intracellular catabolism of radiolabeled anti-mu antibodies by malignant B-cells.

The endocytosis and degradation of 125I-labeled anti-mu monoclonal antibody DA4-4 by a Burkitt's lymphoma cell line was investigated using biochemical, chromatographic, electrophoretic, radioautographic, and electron microscopic techniques. 125I-DA4-4 was rapidly internalized by Ramos cells and routed from endosomes to lysosomes. Proteolysis of radiolabeled antibodies began in a late endosomal compartment, but lysosomes were primarily responsible for the terminal degradation of 125I-DA4-4. Catabolism of 125I-DA4-4 could be inhibited by 74-95% by blocking its delivery to late endosomes and lysosomes by incubation at 18 degrees C, by neutralizing the pH in intracellular organelles with monensin or ammonium chloride, or by inhibiting lysosomal enzymes with leupeptin. Radiolabeled antibodies synthesized using the chloramine T or Iodo-Gen techniques were degraded three times faster than conjugates made using a nonmetabolizable 125I-tyramine cellobiose adduct. Five major intermediate metabolites (Mr 48,000, 42,000, 25,000, 15,000, and 10,000) were generated during the intracellular catabolism of 125I-DA4-4, but 125I-tyrosine was responsible for 95% of the small-molecular-weight metabolites released by cells into the culture medium. We anticipate that a full comprehension of the catabolism of radiolabeled antibodies by tumor cells will make possible the development of clinical interventions which will enhance the retention of radioimmunoconjugates by hematologic malignancies and improve the efficacy of radioimmunotherapy.

Animals↗
PubMed1992

Radiolabeled antibody targeting of the HER-2/neu oncoprotein.

The HER-2/neu oncogene encodes a Mr 185,000 transmembrane phosphoglycoprotein which is overexpressed in 25-35% of breast and ovarian neoplasms and portends a poor prognosis. We have studied the feasibility of targeting this oncoprotein, designated p185, with radioiodinated murine monoclonal antibodies (muMABs) 4D5 and 7C2, which recognize distinct epitopes on its extracellular domain. The rates of internalization and catabolism of these antibodies were analyzed by cellular radioimmunoassay and electron microscopy. After binding to NIH3T3 HER-2/neu cells, which show high surface expression of p185, the muMABs were endocytosed via coated pits, routed to lysosomes, and degraded. Approximately 44% of 125I-4D5 and 39% of 125I-7C2 were catabolized by tumor cells after 24 h. The biodistribution of radiolabeled 4D5 and 7C2 were evaluated in beige/nude mice bearing s.c. NIH3T3 HER-2/neu grafts. A high specificity of localization was seen with tumor:organ ratios of activity generally ranging from 5:1 to 30:1. However, the percentage injected dose of radioactivity per gram of tumor declined sharply from 25% at 24 h to 5% at 120 h postinjection. Treating the animals with 400-700 muCi 131I-4D5 caused a marked inhibition of tumor growth, although no mice were cured. Unlabeled 4D5 had no effect on tumor progression in this model, but administering 400-700 muCi of 131I-DA4-4, an isotype-matched irrelevant muMAB, resulted in an intermediate degree of growth retardation. Analysis of kinetic blood data and whole-body time-activity curves indicated that the irrelevant conjugate remained in the body 2-3 times longer than 131I-4D5. Radioiodinated anti-HER-2/neu muMABs are attractive agents for radioimmunodiagnosis and radioimmunotherapy of aggressive HER-2/neu-positive breast and ovarian carcinomas, but effective strategies for retarding intratumoral catabolism may be necessary to optimize their clinical utility.

3T3 Cells↗
PubMed1992

A controlled study of lymphocyte subsets in rheumatoid arthritis.

The purpose of this study was to determine if patients with rheumatoid arthritis (RA) exhibited unique patterns of peripheral blood lymphocyte (PBL) subsets in comparison to patients with osteoarthritis (OA) and, further, if such differences related to disease activity or nondisease factors. Data from 63 RA patients and 47 OA patients revealed that the RA patients had lower absolute numbers of CD2+ and CD4+ lymphocytes. Small differences also were found in selected B-cell subsets and subsets of lymphocytes expressing CD16 and/or CD57 antigens. Further analysis revealed that these differences were due primarily to the effects of cytotoxic medications in the RA group. However, there were also alterations in some subsets independent of medication groups. PBL subsets in RA patients did not relate to chronic low-dose prednisone or measures of disease activity. This study demonstrated the need to control carefully for variables such as age and medication in immunophenotypic investigations of RA.

Aging↗
PubMed1992

Staphylococcus aureus microcapsule expression attenuates bacterial virulence in a rat model of experimental endocarditis.

The virulence of the Staphylococcus aureus strains that differed only in capsule expression was compared in a rat model of catheter-induced experimental endocarditis. The ID50 of all the strains was low (less than 3 x 10(3) cfu of S. aureus), suggesting that this model may be more sensitive than other animal models to differences in bacterial virulence. Compared with the wild-type strains that expressed type 5 or type 8 capsular polysaccharides, mutant strains devoid of capsule had significantly lower ID50 values. In contrast, a mutant that produced scant amounts of the type 5 polysaccharide had an ID50 similar to that of the parental type 5 isolate. As the bacterial inoculum was increased, each of the S. aureus strains reached final concentrations of 10(10)-10(11) cfu/g of vegetation; however, the nonencapsulated mutants colonized the left-sided vegetations at lower inocula than did the wild-type strains. This study indicates that microcapsule expression attenuates bacterial virulence in a rat model of catheter-induced endocarditis.

Animals↗
PubMed1992

Spontaneous coping strategies to manage acute pain and anxiety during electrodiagnostic studies.

Electrodiagnostic studies produce both anxiety and pain, which can prevent adequate examination and limit the usefulness of test results. This study examined the spontaneous coping strategies used to manage the pain and anxiety experienced during electrodiagnostic testing. Fifty patients (26 women and 24 men) evaluated in our electrodiagnostic laboratory were administered visual analogue scale (VAS) pain and anxiety measures and the Spielberger State-Trait Anxiety Inventory (STAI) before the procedure. Immediately after the procedure, subjects reported pain, anxiety, and coping strategies used during electrodiagnostic testing using the VAS, the STAI, and a situation-specific version of the Coping Strategies Questionnaire (CSQ-S). The CSQ-S appears to be a valid and reliable measure of spontaneous coping strategies. Multiple-regression analyses revealed that frequent use of catastrophizing, diverting attention, and coping self-statement strategies was significantly and positively correlated with pain, whereas reinterpreting pain was significantly and negatively associated with pain. Judgments of control over pain were also significantly and negatively associated with anxiety experienced during electrodiagnostic studies. Physicians' ratings of pain and anxiety were highly correlated with patients' self-reports. This study suggests that ineffective coping strategies may enhance the pain and anxiety experienced during electromyography. Alternatively, teaching subjects active self-control skills and increasing patients' self-efficacy beliefs may help manage this situation-specific acute anxiety and, possibly, the associated pain.

Adaptation, Psychological↗
PubMed1991

Intracellular catabolism of radiolabeled anti-CD3 antibodies by leukemic T cells.

The endocytosis and intracellular metabolism of radiolabeled anti-CD3 MoAb 64.1 by the malignant human T cell line HPB-ALL were studied using biochemical, morphological, electrophoretic, and chromatographic techniques. Biosynthetically labeled [3H]64.1 and externally radioiodinated 125I-64.1 were similarly internalized and degraded by tumor cells, with approximately 70% of the initially bound radioactivity being released to the culture supernatant as trichloroacetic acid-soluble radioactivity in the first 24 hr of culture. Radiolabeled 64.1 was routed from the cell membrane to endosomes where initial proteolysis began and finally to lysosomes where terminal catabolism to single amino acids occurred. SDS-PAGE demonstrated four major intracellular metabolite species (46, 25, 15, and less than 10 kDa). Thin-layer chromatography demonstrated that greater than 95% of the trichloroacetic acid-soluble radioactivity in culture supernatants was 125I-monoiodotyrosine, indicating that proteases, not deiodinases, were of primary importance in catabolism of 125I-64.1. In the presence of inhibitors of lysosomal function (leupeptin, monensin, and ammonium chloride), 125I-64.1 degradation was impeded, causing prolonged retention of radioactivity in the lysosomal compartment of cells. However, although the pace of catabolism was markedly diminished by these agents, no major changes in the sizes of intermediate metabolites generated were observed. Our results suggest that judicious administration of lysosomal inhibitors (e.g. chloroquine, verapamil, monensin) may significantly enhance retention of radioimmunoconjugates by lymphoid malignancies, improving radioimmunoscintigraphic and radioimmunotherapeutic efforts.

Ammonium Chloride↗
PubMed1991

Comparison of a computer tutorial with other methods for teaching well-newborn care.

Research using a computer-assisted instructional program developed for teaching well-newborn care is described. Third-year medical students were randomly assigned during their week-long nursery rotation into three groups to study the acceptability and effectiveness of using the computer-assisted instructional lessons. Group A, the control group, was not required to complete any additional educational task. Group B was assigned specific reading material. Group C completed the microcomputer-based tutorial. (The term tutorial is often used interchangeably to describe the computer-assisted instructional program.) Both groups B and C improved dramatically on a posttest in comparison with group A. There was no statistically significant difference between groups B and C on the improvement from pretest to posttest scores. However, significantly less time was spent by group C completing the tutorial compared with the total time spent reading by group B. The results of this study provide further illustration of the feasibility and effectiveness of using a computer-assisted instructional program for medical student education.

Attitude to Computers↗
PubMed1991

Association of immunoglobulin Km and Gm allotypes with specific antinuclear antibodies and disease susceptibility among connective tissue disease patients.

The distribution of the immunoglobulin Km(1) and Gm phenotypes was examined in patients with connective tissue diseases, including systemic lupus erythematosus, mixed connective tissue disease, and scleroderma, whose sera were characterized for antibodies against nuclear antigens and polypeptides of U small nuclear ribonucleoproteins. We found a strong association between Km(1) phenotype and susceptibility to systemic lupus erythematosus (P less than 0.00001, relative risk = 17). We also found a positive association between the Km(1) phenotype and the presence of anti-double-stranded DNA antibodies. The presence of certain immunoglobulin genes or gene families may have a role in susceptibility to the development of autoantibodies and/or of connective tissue disease.

Antibodies, Antinuclear↗
PubMed1991

Biopsychosocial parameters of disease activity in rheumatoid arthritis.

The purpose of this study was to examine the applicability of a biopsychosocial model for estimating disease activity in rheumatoid arthritis (RA). Sixty-three patients with RA were evaluated at baseline, 3 months, and 6 months. Joint counts were collected as the measure of disease activity. Peripheral blood immunophenotypic subsets, demographic characteristics, and psychological measures were obtained and entered into hierarchical regression analyses, with the joint count as the dependent variable. Immunophenotypic subsets (that is, CD57+/CD16-, HLA-DR+) were predictive of disease activity at all three time intervals. At baseline and 3 months, psychological variables (that is, helplessness and depression) were significantly related to joint counts, and the full model was highly significant. The conclusion was that the biopsychosocial perspective is useful for estimating RA disease activity.

Aged↗
PubMed1991

Early angioplasty in patients with acute myocardial infarction complicated by hypotension.

Emergency percutaneous transluminal coronary angioplasty was performed in 62 patients with acute myocardial infarction complicated by hypotension. All patients were treated within 12 hours of the onset of chest pain. Angioplasty was completely successful (residual lesion less than or equal to 50%) in 48 patients, partially successful (patent vessel greater than 50% residual lesion) in four patients, and unsuccessful in 10 patients. Patients in whom angioplasty was successful had a hospital mortality rate of 19%; those in whom angioplasty was unsuccessful or only partially successful had hospital mortality rates of 60% and 50%, respectively, (p = 0.012). Patients with occlusion of the proximal left anterior descending vessel had the highest failure rate (42%) and the highest mortality rate (67%). Other univariate predictors of hospital mortality were older age and elevated end-diastolic pressure. Successful emergency angioplasty improves mortality in patients with acute infarction complicated by hypotension.

Angioplasty, Balloon, Coronary↗
PubMed1991

Antigenic domains on the U1 small nuclear ribonucleoprotein-associated 70K polypeptide: a comparison of regions selectively recognized by human and mouse autoantibodies and by monoclonal antibodies.

Antigenic regions on the U1 small nuclear ribonucleoprotein (snRNP)-associated 70K polypeptide recognized by human and mouse autoantibodies or by monoclonal antibodies were identified and compared. Using a set of 70K fusion proteins as antigen in enzyme-linked immunosorbent assay and immunoblotting revealed that serum autoantibodies of human and of MRL/Mp mouse origin recognized a common region of the 70K polypeptide. Monoclonal anti-70K antibodies derived from a patient with mixed connective tissue disease, from an autoimmune MRL/Mp mouse, and from a BALB/c mouse immunized with purified U1 snRNP were all shown to bind to a part of the 70K polypeptide rich in charged residues and different from the region recognized by most human and MRL/Mp mouse serum autoantibodies.

Animals↗
PubMed1991

Cellular ras gene activity is required for full neoplastic transformation by polyomavirus.

To investigate the role of ras gene activity in cellular transformation by polyomavirus, murine C3H10T1/2 cells were rendered ras deficient by transfection with an antisense ras gene construct. Ras deficiency resulted in a partial suppression of the polyomavirus-induced transformed phenotype. The production of viral middle T antigen and its association with pp60c-src, increased membrane-associated protein kinase C activity, and morphological transformation were unaffected by the downregulation of c-ras gene expression. On the other hand, stimulated proliferation, focus formation on confluent monolayers of normal cells, and colony formation in soft agar were all greatly reduced in cells containing reduced p21ras levels. It is concluded that ras gene activity is needed for full cell transformation by polyomavirus.

Animals↗