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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 235 records · Page 13Linked to original sources
PubMed1996

Defective B cell development in Snell dwarf (dw/dw) mice can be corrected by thyroxine treatment.

Snell dwarf (dw/dw) mice are deficient in anterior pituitary hormones due to a mutation in the gene encoding the Pit-1 transcription factor. Bone marrow B cell development is also suppressed in the mice, providing circumstantial evidence that one or more anterior pituitary-derived products, or factors induced by them, are required for normal B lymphopoiesis. However, concluding that this is the case is dependent on showing that hormonal treatment of dwarf mice reverses their B cell defects. dw/dw mice were treated with growth hormone (GH), insulin-like growth factor-I (IGF-I), or thyroxine in an attempt to restore bone marrow B lymphopoiesis. GH and IGF-I increased the number of B lineage cells in the bone marrow and spleen but did not restore the frequency of bone marrow pre-B cells to normal. However, bone marrow cellularity in thyroxine-treated dw/dw mice was comparable to that in control animals, and both the frequency and absolute number of B lineage cells had increased to normal or even above normal. Taken together, these data indicate that endocrine factors, especially those regulated by the hypothalamic-pituitary-thyroid axis, are potent B lymphopoietic factors.

Animals↗
PubMed1996

The carboxyl terminus of GLUT4 contains a serine-leucine-leucine sequence that functions as a potent internalization motif in Chinese hamster ovary cells.

To characterize the trafficking motifs contained in the carboxyl terminus of GLUT4, a chimera (GTCTR) was constructed in which the carboxyl-terminal 30 amino acids of GLUT4 were substituted for the amino-terminal cytoplasmic domain of the transferrin receptor (TR). The endocytic behavior of this chimera was characterized in Chinese hamster ovary cells. The GTCTR chimera had a more predominant intracellular distribution compared to the TR. Only 20% of the GTCTR chimera is on the surface at steady-state compared to 35% of the TR. The GTCTR chimera is internalized 50% more rapidly and recycled 20% more slowly than the TR. Acidification of the cytosol inhibited internalization of the GTCTR chimera, indicating that the chimera is internalized through clathrin-coated pits. Mutations of GTCTR were constructed in which a di-leucine sequence of the carboxyl domain of GLUT4 was mutated to a di-alanine sequence (GTCTR-AA) and serine residue 488, immediately preceding the di-leucine sequence, was mutated to either an alanine or aspartate residue. In each case, albeit to varying degrees, the substitutions shifted the distribution of the mutated GTCTR constructs toward the surface. The shift in the distribution of GTCTR-AA resulted from a 10-fold reduction in internalization, and the shift of serine 488 mutants resulted from a 3-fold reduction in the internalization rate compared to GTCTR. None of these mutations affected the recycling rate. These results demonstrate that the carboxyl terminus of GLUT4 contains a serine-leucine-leucine-based motif that, when expressed in non-insulin responsive cells, functions as a potent internalization motif which promotes more rapid internalization than does the native TR internalization motif.

Amino Acid Sequence↗
PubMed1996

Gun acquisition and use by juvenile offenders.

OBJECTIVES: To learn how, when, where, and why juvenile offenders acquire guns. DESIGN: Following acquisition of informed consent, we conducted semistructured interviews between June and November 1995 with a convenience sample of 63 juvenile offenders aged 13 through 18 years, each of whom was incarcerated at a detention center in metropolitan Atlanta, Ga. SETTING: Five detention centers in metropolitan Atlanta. MAIN OUTCOME MEASURES: Frequency of handgun acquisition and use, age at and method of first handgun acquisition, feelings experienced when carrying guns, development of gun-carrying behavior, drug use, and gang membership. RESULTS: The mean age of respondents was 15.7 years. Forty-one male and 12 female respondents had owned a gun. Eighty-four percent of gun carriers acquired their first gun before the age of 15 years; more than half received their first gun passively, without any specific plan to do so. Adolescents who purposefully obtained their first handgun were more likely to become frequent or constant carriers. Forty percent felt safer and 40% said they felt more energized, excited, or powerful while carrying a gun. However, 34% reported increased anxiety about getting caught. Almost all stated that guns are readily available from a wide range of sources. CONCLUSION: Knowledge of the developmental patterns of gun carrying by delinquent adolescents could be useful in formulating effective strategies to reduce firearm violence.

Adolescent↗
PubMed1996

Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance.

To test the hypothesis that obesity/insulin resistance impairs both endothelium-dependent vasodilation and insulin-mediated augmentation of endothelium-dependent vasodilation, we studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of methacholine chloride (MCh) or sodium nitroprusside (SNP) during saline infusion and euglycemic hyperinsulinemia in lean insulin-sensitive controls (C), in obese insulin-resistant subjects (OB), and in subjects with non-insulin-dependent diabetes mellitus (NIDDM). MCh induced increments in LBF were approximately 40% and 55% lower in OB and NIDDM, respectively, as compared with C (P < 0.05). Euglycemic hyperinsulinemia augmented the LBF response to MCh by - 50% in C (P < 0.05 vs saline) but not in OB and NIDDM. SNP caused comparable increments in LBF in all groups. Regression analysis revealed a significant inverse correlation between the maximal LBF change in response to MCh and body fat content. Thus, obesity/insulin resistance is associated with (a) blunted endothelium-dependent, but normal endothelium-independent vasodilation and (b) failure of euglycemic hyperinsulinemia to augment endothelium-dependent vasodilation. Therefore, obese/insulin-resistant subjects are characterized by endothelial dysfunction and endothelial resistance to insulin's effect on enhancement of endothelium-dependent vasodilation. This endothelial dysfunction could contribute to the increased risk of atherosclerosis in obese insulin-resistant subjects.

Adult↗
PubMed1996

Psychological symptoms and disease-free and overall survival in women with stage II breast cancer. Cancer and Leukemia Group B.

BACKGROUND: The possible link between psychological factors and length of cancer survival has generated a literature of contradictory findings. Associations usually have not been found when general psychological symptoms are assessed. Associations usually have been found for predictors related to expressive versus repressive emotional coping (e.g., depression, "fighting spirit," hostility, and type C personality); however, even these associations have been relatively small, when compared with those for medical factors. Yet few studies have adequately controlled for medical and treatment-related factors. PURPOSE: Within a Cancer and Leukemia Group B (CALGB) national clinical trial of four adjuvant therapy regimens for stage II breast cancer (CALGB 8082), this study prospectively examined the contribution of potential psychological predictors to length of disease-free and overall survival over a 15-year period. METHODS: Subjects were 280 women with stage II breast cancer, out of a total of 899, who were randomly assigned to receive CMFVP (cyclophosphamide-methotrexate-fluorouracil-vincristine-prednisone) for two 6-week cycles or six 4-week cycles, then subsequently randomly assigned to receive or not to receive VATH (vinblastine-doxorubicin-thiotepa-fluoxymesterone). Subjects were recruited during the period between October 1980 and August 1984, inclusive, and followed until January 1996. Prior to chemotherapy, psychological symptoms were assessed using the Symptom Check List-90-Revised (SCL-90-R). SCL-90-R scores were trichotomized into categories representing high, medium, and low distress. Basic base-line sociodemographic data (including age, ethnicity, education, and marital status) and medical data (including lymph node status, estrogen receptor status, menopausal status, and performance status) were collected. Subjects with psychosocial data differed from those without psychosocial data solely in their higher percentage of classification in the mild limitation category of the Zubrod (Eastern Cooperative Oncology Group) performance status rating (subjects with psychosocial data: 14%; subjects without psychosocial data: 8%). RESULTS: In stepwise Cox regression analyses that controlled for sociodemographic and medical variables, there was no significant predictive effect of the level of distress (as measured by the SCL-90-R trichotomized scores) on length of disease-free and overall survival of the study subjects. Risk ratios for low versus high distress were 1.01 (95% confidence interval [CI] = 0.62-1.66) for disease-free survival and 1.03 (95% CI = 0.58-1.82) for overall survival. CONCLUSIONS: This study failed to provide evidence that psychological factors contributed to length of disease-free or overall survival of women who received adjuvant chemotherapy (either CMFVP alone or CMFVP followed by VATH) for treatment of stage II breast cancer. IMPLICATIONS: In the context of far more potent medical factors, the contribution of psychological factors to disease-free and overall survival is likely to be relatively small. Future research should focus on specific theory-driven predictors rather than on general psychological symptoms. Moreover, it should be based on clinical studies using a controlled, prospective design, in which the effects of medical factors may be distinguished and psychological predictors are clear antecedents of survival outcomes.

Adaptation, Psychological↗
PubMed1996

Thymic stromal cells can support B cell differentiation from intrathymic precursors.

T lineage cells are the predominant intrathymic population, but low numbers of thymic B cells are also present in the thymus. Recent studies describing the contribution of thymic B cells to the shaping of the T cell repertoire have raised the question as to whether they are produced intrathymically and the potential role of the thymic stroma in this process. During the course of studies aimed at testing the B cell developmental potential of CD4-CD8-CD3/TCR- triple-negative thymocytes present in a newly developed, stromal cell-dependent, long term culture system, the ability of selected thymic stromal cells to support distinct stages of B cell development was revealed. Some thymic stromal cell lines maintained cells with B cell developmental potential but could not support their differentiation, while other selected lines efficiently supported the development of surface IgM-expressing cells from triple-negative precursors. Thymic surface IgM+ B cells were generated most efficiently from thymocytes harvested from relatively young mice. Taken together, the results of this study demonstrate that the thymic microenvironment exhibits a functional heterogeneity in its ability to support different stages of B cell development.

Aging↗
PubMed1996

Percutaneous transluminal coronary angioplasty: comparison of arterial vs. venous activated clotting time.

When arterial blood samples for activated clotting time (ACT) are difficult to obtain from the arterial sheath during coronary intervention, venous ACT serves as a substitute. Data are lacking on whether arterial and venous ACT are identical and whether one can serve as an effective substitute for the other. Forty-eight patients undergoing percutaneous transluminal coronary angioplasty (PTCA) were prospectively evaluated to answer this question. Simultaneous arterial and venous ACT samples were drawn from femoral artery and vein vascular sheaths before and during each procedure, and ACT values were determined with a Hemochron automated electronic timer. Porcine heparin dosing was guided by arterial ACT in the first 25 patients and by venous ACT in the last 23 patients. The target ACT value used for continued heparin dosing was 400 sec. At baseline and throughout the study up to 60 min, venous ACT was slightly and significantly greater than arterial ACT. Despite this statistical difference in ACT values, there was no difference in complication rate between the two groups, and the amount of heparin used during either guiding regimen was the same. Therefore, although venous ACT values are slightly higher than arterial, the more convenient venous ACT can be safely used to guide heparin dosing during PTCA when using a target ACT value of 400 sec.

Adult↗
PubMed1996

Differentiation of sarcoidosis from tuberculosis by use of electron capture gas-liquid chromatography.

To explore further the possible etiologic role of mycobacteria in the development of sarcoidosis, we measured free, nonbound tuberculostearic acid (TSA, 10-methyloctadecanoic), a component of mycobacteria, in the sera of subjects with sarcoidosis or active untreated pulmonary tuberculosis and in healthy controls by use of frequency-pulsed electron capture gas-liquid chromatography (FPEC-GLC). The selective analytic system is capable of measuring as little as 15-fmol quantities of free, nonbound TSA in serum and cerebral spinal fluid. We found that TSA was present in the sera of all subjects with Mycobacterium tuberculosis (n = 10) but was undetectable in subjects with sarcoidosis (n = 15) and in healthy controls (n = 15), thereby suggesting that if sarcoidosis is caused by a mycobacterial organism, TSA is not produced or does not gain access to the systemic circulation in quantities sufficient for measurement. However, in the course of the studies we found that a peak, designated p11, was elevated in the sera of all subjects with acute sarcoidosis (n = 4). Also, a peak designated p3 was reduced significantly in all subjects with acute and chronic sarcoidosis and absent in subjects with M. tuberculosis compared with healthy controls. Both peaks were later shown by chemical analysis and mass spectral studies to be carboxylic acids not previously associated with specific disease entities. Follow-up detailed studies will be needed to determine if quantitation of these unique carboxylic acids will be useful in differentiating sarcoidosis from other disorders.

Carboxylic Acids↗
PubMed1996

Lipoprotein composition in NIDDM: effects of dietary oleic acid on the composition, oxidisability and function of low and high density lipoproteins.

Oxidation of low density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis and is related to the fatty acid composition which is altered in diabetes mellitus. This study examines the relationship between the fatty acid composition of LDL and high density lipoprotein (HDL) and lipoprotein oxidation. A group of nine non-insulin-dependent diabetic (NIDDM) patients were compared to seven healthy control subjects before and after a high monounsaturated diet. Lipoproteins were isolated and oxidisability was measured by conjugated diene formation and lipid peroxide analysis. Serum HDL cholesterol was significantly lower in the diabetic patients. LDL cholesteryl ester linoleic acid in the diabetic patients was significantly higher at baseline and decreased after diet (p < 0.05) while oleic acid increased in both diabetic and non-diabetic subjects (p < 0.05). HDL cholesteryl ester oleic acid was lower in the diabetic patients compared with control subjects (p < 0.05) before diet and it increased significantly after diet (p < 0.05). LDL lipid peroxides and conjugated diene formation were related to LDL glycation (r = 0.46, p < 0.05 and r = 0.49, p < 0.05, respectively). Both decreased following diet (lipid peroxides for diabetic patients from 476 +/- 30 to 390 +/- 20 nmol/mg protein p < 0.05 and for control subjects from 350 +/- 36 to 198 +/- 30 nmol/mg protein p < 0.05). HDL conjugated diene formation decreased in both groups after diet but only significantly in the control group (55.4 +/- 7.5 to 53.2 +/- 6.7 nmol/mg protein for diabetic patients and 45.8 +/- 6.4 to 31.6 +/- 4.8 nmol/mg protein p < 0.05 for control subjects). There was a positive correlation between LDL lipid peroxide formation and percentage of cholesteryl ester linoleic acid in LDL from diabetic patients (r = 0.61, p < 0.05) and control subjects (r = 0.91, p < 0.01). Fatty acid composition of LDL was reflected in the composition of HDL. In the presence of HDL lipoprotein peroxidation decreased. This decrease in lipoprotein peroxidation was positively related to the percentage of linoleic acid in LDL (r = 0.71, p < 0.05). This study confirms the close relationship between the fatty acid composition of LDL and HDL and demonstrates the importance of the fatty acid composition of the cholesteryl ester fraction in relation to LDL oxidation in diabetes. Linoleic acid in HDL appears to be a protecting factor against oxidation.

Adult↗
PubMed1996

Elevated triglyceride-rich lipoproteins in diabetes. A study of apolipoprotein B-48.

The role of the intestine in cholesterol metabolism in human diabetes is unclear, although abnormalities have been demonstrated in cholesterol synthesis and absorption in diabetic animals. This study examines the relationship between fasting and post-prandial apolipoprotein B-48 in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Eight type 2 diabetic patients and ten healthy non-diabetic control subjects were given a high-fat meal (1300 kcal), and the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (d < 1.006 g/ml) from fasting and post-prandial plasma. Apolipoprotein B-48 and apo B-100 were separated on 4%-15% gradient gels and quantified by densitometric scanning with reference to a purified low-density lipoprotein (LDL) apo B-100 preparation. Diabetic patients had significantly higher concentrations of apo B-48 and apo B-100 in both the fasting (P < 0.05) and post-prandial (P < 0.001) triglyceride-rich lipoprotein samples compared with non-diabetic subjects. The diabetic patients also exhibited a significantly different post-prandial profile for apo B-48 and apo B-100, with a prolonged increase and a later post-prandial peak, than the non-diabetic subjects (P < 0.01). These results suggest that the raised fasting triglyceride-rich lipoproteins, often found in diabetes, are associated with apo B-48 and may be derived from increased intestinal chylomicron production. The post-prandial pattern suggests an abnormality in intestinal production as well as hepatic clearance of apo B-48 in type 2 diabetes.

Apolipoprotein B-100↗
PubMed1996

Flow cytometric analysis of 68 monoclonal anti-D reagents.

68 monoclonal IgG anti-D were assessed for quantitative and qualitative binding to D variant red cells using a flow cytometric indirect immunofluorescence test. One antibody failed to bind to normal RhD pos. cells, but reacted weakly with D cat VI and D Cat VII cells. Quantitatively, binding varied approximately twenty-fold between different MAbs and different D variants. D cat III cells gave the lowest level of binding when compared with the D pos. controls. Qualitatively, R1VIr, R2VIr, R1VIIr and DFR samples failed to react with various MAbs regardless of the levels of binding of these MAbs to the D pos. controls, thus supporting the idea of missing epitopes in such variants.

Antibodies, Monoclonal↗
PubMed1996

A cost-effectiveness analysis of neonatal ECMO using existing evidence.

A cost-effectiveness analysis is part of the U.K. ECMO Trial. In preparation for this analysis, existing evidence on the costs and effectiveness of neonatal ECMO was evaluated. ECMO appears to be more costly but may be more or less effective than conventional treatment. No case can be made for introducing ECMO before trial results are available.

Cost-Benefit Analysis↗
PubMed1996

Total quality management practices in the NSW hospital system--an overview.

A two-phase descriptive study involving a questionnaire survey was undertaken during 1994 and 1995 to evaluate the extent of implementation of total quality management practices in New South Wales hospitals accredited by the Australian Council on Healthcare Standards. A survey response rate of 72 per cent was attained. Results indicated that most hospitals were aware of and consciously implemented aspects of the total quality management philosophy in some way. There is little evidence that whole systems have embraced the total quality management approach as a fully integrated endeavour.

Community-Institutional Relations↗
PubMed1996

Non-insulin-dependent diabetes mellitus: dietary monounsaturated fatty acids and low-density lipoprotein composition and function.

Alterations in low-density lipoprotein (LDL) composition in diabetes affect its function with respect to control of de novo cholesterol synthesis. We examined the effect of 4 weeks of an oleic-acid-rich diet on LDL composition and function in eight Type 2 diabetic and eight non-diabetic control subjects. LDL (density 1.019-1.063 g/l) was isolated by sequential ultracentrifugation. LDL composition was measured and LDL fatty acids were determined by gas liquid chromatography. Cholesterol synthesis was measured by [14C]-acetate incorporation into the freshly isolated mononuclear leucocytes. Fasting blood glucose fell from 9.3 +/- 2.0 to 8.2 +/- 1.2 mmol/l (p < 0.05) and fasting serum insulin increased from 8.3 +/- 2.8 to 10.4 +/- 5.0 mIU/l (p > 0.05) in the diabetic patients. LDL oleic acid increased in the diabetic patients from 18.8 +/- 1.8% to 22.5 +/- 1.9% (p < 0.01) and in the non-diabetic subjects from 19.9 +/- 1.8% to 23.3 +/- 2.8% (p < 0.01). The LDL-esterified to free cholesterol ratios of 3.0 +/- 0.6 and 2.7 +/- 0.2 for the diabetic and non-diabetic patients were similar, and decreased significantly (p < 0.01) to 2.4 +/- 0.5 and 2.2 +/- 0.4, respectively. Baseline [14C]-acetate incorporation was similar in the two groups, and decreased after diet from 437 +/- 239 to 249 +/- 144 ng/g cell protein (p < 0.05) in the diabetic patients. There was a negative correlation between the LDL-esterified to free cholesterol ratio and the ratio of oleic to linoleic acid in the LDL (r = -0.39, p < 0.05) and a negative correlation between fasting blood glucose and LDL oleic acid in the diabetic patients (r = -0.51, p < 0.05). Enrichment of LDL with oleic acid appears to improve its ability to regulate endogenous cholesterol synthesis in both control and diabetic subjects. In the diabetic population, the diet had a favourable effect on glycaemic control.

Acetates↗