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Biomedical subjects

B Wright

Publications and source records attributed to B Wright.

At least 73 records · Page 4Linked to original sources
PubMed1996

CD30 ligand expression in nonmalignant and Hodgkin's disease-involved lymphoid tissues.

The CD30 ligand (CD30L) is a type II transmembrane glycoprotein of the tumor necrosis factor ligand superfamily. Recent cloning of CD30L has enabled studies to explore its function and tissue distribution. For instance, recombinant CD30L has been shown to co-stimulate T cells and to act as mitogen for Hodgkin's disease (HD)-derived cell lines. The counter-receptor for CD30L, ie, CD30, is a type I cytokine receptor that is highly expressed by activated T cells, Hodgkin and Reed-Sternberg (H-RS) cells, and anaplastic large cell lymphoma cells. In the present study, recombinant membrane-bound and soluble human CD30L were instrumental to raise a monoclonal antibody (M80) recognizing membrane-bound CD30L on transfected and native cells. With this reagent, a panel of cultured lymphoma-derived cell lines as well as primary normal, reactive, and HD-involved lymphoid tissues were examined for expression of CD30L by immunostaining and flow cytometry. In reactive lymphnodes and tonsils, CD30L was expressed by a small subset of lymphoid cells, histiocytes, and granulocytes. Higher levels of CD30L expression were noted in HD lesions among bystander cells; ie, T cells and granulocytes that surrounded H-RS cells. Native CD30L displayed at the cell surface was functionally active as shown by the ability of fixed granulocytes to interact with CD30+ cell lines. Moreover, CD30L was detectable, although to a lower staining intensity, in primary H-RS cells of all HD tissues investigated regardless of the histological subtype and the phenotype of H-RS cells (ie, CD30+/CD40+ versus CD30-/CD40+). Co-expression of CD30 and CD30L that was seen on H-RS cells of all, except the CD30- nodular lymphocyte predominant, subtypes of HD may point to the use of this pair of molecules in paracrine and/or autocrine mitogenic cell interactions. Monoclonal antibody M80 may thus represent a useful tool for studying CD30L expression on cultured cell lines and primary cells from normal, reactive, and malignant tissues.

Antibodies, Monoclonal↗
PubMed1996

Dilemmas.

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Conflict, Psychological↗
PubMed1995

Combination therapy with recombinant human soluble CD4-immunoglobulin G and zidovudine in patients with HIV infection: a phase I study.

To determine the effect of zidovudine (ZDV) on the pharmacokinetic disposition of recombinant soluble CD4 immunoglobulin G (rCD4-IgG) and to evaluate the safety and preliminary activity of concurrent administration of ZDV with rCD4-IgG, we undertook an open-label, dose-escalating, 12-week study. The regimens of intravenous rCD4-IgG and oral ZDV we used were (a) 300 micrograms/kg rCD4-IgG twice per week and 300 mg ZDV per day, (b) 300 micrograms/kg rCD4-IgG twice per week and 600 mg ZDV per day, (c) 1,000 micrograms/kg rCD4-IgG twice per week and 300 mg ZDV per day, (d) 1,000 micrograms/kg rCD4-IgG twice per week and 600 mg ZDV per day, and (e) 3,000 micrograms/kg rCD4-IgG twice per week and 300 mg ZDV per day. Subjects were recruited from three AIDS clinical trials units. Forty-one patients with HIV infection who had CD4 cell counts < or = 500 cells/mm3 and < 120 days of previous ZDV therapy participated. Pharmacokinetic interactions were assessed with the second regimen. Mean calculated peak serum rCD4-IgG concentrations were 5.47 micrograms/ml with ZDV and 8.28 micrograms/ml without ZDV, with serum half-lives of 34.2 and 32.0 h, respectively. Antibodies to rCD4-IgG were not detected. Seven episodes of severe adverse events occurred in five patients: one episode each of severe nausea, fever, or abnormal liver function tests and four episodes of severe neutropenia. Mean hemoglobin and neutrophil counts decreased, and mean platelet counts increased in all regimens, but there were no significant differences among regimens, rCD4-IgG dose, or ZDV dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Pharmacokinetics of single- and multiple-dose bupropion in elderly patients with depression.

A study of a dopaminergic antidepressant that may have an advantageous profile for use in elderly patients, bupropion, was conducted to determine the pharmacokinetics of bupropion in the elderly. Pharmacokinetics of single- and multiple-dose bupropion were examined in six elderly patients (five women and one man) diagnosed with depression. Mean (+/- SD) CL app of bupropion was 1.6 +/- 0.4 L/hr/kg, approximately 80% of the corresponding value reported for younger patients. Mean bupropion t1/2 was 34.2 +/- 8.7 hours, and average apparent Vd (Vd app) was 79.3 +/- 29.4 L/kg. Apparent half-lives (t1/2 app) of the metabolites hydroxybupropion, erythrobupropion, and threohydrobupropion were 34.2 +/- 4.6 hours, 61.4 +/- 21.6 hours, and 38.8 +/- 7.6 hours, respectively. After multiple dosing, the mean t1/2 for bupropion and its metabolites did not change significantly, although in some patients the t1/2 app of the metabolites was substantially prolonged. There was also evidence of inordinate accumulation of metabolites. The elderly are at risk for accumulation of bupropion and its metabolites. Specification of therapeutic drug monitoring parameters for bupropion treatment of the elderly is needed.

Administration, Oral↗
PubMed1995

Heroes.

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Emergency Nursing↗
PubMed1995

Measuring the fetal kidney with ultrasonography.

OBJECTIVES: To establish a normal range of measurements for the external and internal dimensions of the fetal kidney and, if possible, to correlate these measurements with gestational age. SUBJECTS AND METHODS: The external and internal dimensions of the fetal kidney were measured in 810 women selected on the grounds of obstetric, fetal or technical risk factors from a consecutive series of 1136 women attending the ante-natal ultrasonography clinic of a district general hospital. Post-natal data were obtained from medical records on 1122 newborns. The maximum of pairs of renal measurements was used for analysis. Measurements were cross-sectional in 347 cases and longitudinal in 463. The total number of measurement episodes was 2294. RESULTS: External renal dimension and gestational age were closely related, enabling accurate growth centile charts to be constructed. The correlation between renal pelvic dimension and gestational age was weak. The maximum dimension of the renal pelvis at any gestational age in 92.7% of fetuses was < 5 mm. Using longitudinal measurements, 6.5% of cases with a renal pelvic dimension of < 5 mm at the first scan measured > or = 5 mm at a subsequent scan, but 53.3% with a dimension of > or = 5 mm at the first scan also measured > or = 5 mm at the subsequent scan. CONCLUSION: It is possible to assess the growth and size of the fetal kidney according to gestational age but this does not apply to the renal pelvis. A renal pelvic dimension of > 5 mm at any gestational age is unusual and dilatation beyond this level should prompt a detailed post-natal urological investigation.

Female↗
PubMed1995

Dual chamber pacing: how many patients remain in DDD mode over the long term?

OBJECTIVE: DDD pacing is better than VVI pacing in complete heart block and sick sinus syndrome but is more expensive and demanding. In addition, some patients have to be programmed out of DDD mode and this may have an important impact on the cost-effectiveness of DDD pacing. The purpose of this study was to determine how many patients remain in DDD mode over the long term (up to 10 years). DESIGN: A retrospective analysis of the outcome over 10 years of consecutive patients who had their pacemakers programmed initially in DDD mode. SETTING: A district general hospital. PATIENTS: 249 patients with DDD pacemakers. Sixty two patients (24.9%) had predominantly sick sinus syndrome and 180 (72.3%) had predominantly atrioventricular conduction disease. Mean (range) complete follow up for this group of patients was 32 months (1-10 years). RESULTS: Cumulative survival of DDD mode was 83.5% at 60 months. Atrial fibrillation was the commonest reason for abandonment of DDD pacing. Atrial fibrillation developed in 30 patients (12%), with atrial flutter in three (1.2%). Loss of atrial sensing or pacing, pacemaker mediated tachycardia, and various other reasons accounted for reprogramming out of DDD mode in eight patients (3.2%). Overall, an atrial pacing mode was maintained in 91% and VVI pacing was needed in only 9%. CONCLUSIONS: With careful use of programming facilities and appropriate secondary intervention, most patients with dual chamber pacemakers can be maintained successfully in DDD or an alternative atrial pacing mode until elective replacement, although atrial arrhythmia remains a significant problem. There are no good reasons, other than cost, for not using dual chamber pacing routinely as suggested by recent guidelines and this policy can be achieved successfully in a district general hospital pacing centre.

Aged↗
PubMed1995

The effect of DHEA given chronically to Zucker rats.

Dehydroepiandrosterone (DHEA) has been reported to exert antiglucocorticoid activity. When administered to obese, hypercorticosteronemic Zucker rats, it causes a diminution of food intake and a reduction in their rate of weight gain. This experiment was conducted to evaluate whether this biologic effect could be ascribed to chronic adrenal insufficiency. Obese and lean Zucker rats were treated with DHEA as a food supplement for 28 days. Upon sacrifice, organ weights and serum chemistries were measured, along with neurotransmitter levels in regions of the hypothalamus. Results showed that although the obese animals gained weight more slowly, had lower insulin levels, and ate less, their serum glucose, corticosterone, and ACTH levels were not different from control. Hypothalamic neurotransmitters in the obese rat were unaffected by chronic DHEA treatment. We concluded that, although DHEA clearly affects Zucker weight gain, it does not induce chronic adrenal insufficiency.

Adrenal Glands↗
PubMed1994

Humoral immune responses in CD40 ligand-deficient mice.

Individuals with X-linked hyper-IgM syndrome fail to express functional CD40 ligand (CD40L) and, as a consequence, are incapable of mounting protective antibody responses to opportunistic bacterial infections. To address the role of CD40L in humoral immunity, we created, through homologous recombination, mice deficient in CD40L expression. These mice exhibited no gross developmental deficiencies or health abnormalities and contained normal percentages of B and T cell subpopulations. CD40L-deficient mice did display selective deficiencies in humoral immunity; basal serum isotype levels were significantly lower than observed in normal mice, and IgE was undetectable. Furthermore, the CD40L-deficient mice failed to mount secondary antigen-specific responses to immunization with a thymus-dependent antigen, trinitrophenol-conjugated keyhole limpet hemocyanin (TNP-KLH). By contrast, the CD40L-deficient mice produced antigen-specific antibody of all isotypes except IgE in response to the thymus-independent antigen, DNP-Ficoll. These results underscore the requirement of CD40L for T cell-dependent antibody responses. Moreover, Ig class switching to isotypes other than IgE can occur in vivo in the absence of CD40L, supporting the notion that alternative B cell signaling pathways regulate responses to thymus-independent antigens.

Animals↗
PubMed1994

Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease.

CD40 was originally described as a B-cell-restricted antigen and was subsequently found to be a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some carcinoma cell lines, and plays a critical role in cell contact-dependent activation. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the presumed malignant cells of Hodgkin's disease (HD); were found to express high levels of cell surface CD40. We found that recombinant CD40 ligand (CD40L) induced interleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin-alpha (LT-alpha/TNF-beta) release from cultured H-RS cells. These cytokines play a significant role in the clinical presentation and pathology of HD, a tumor of cytokine-producing cells. CD40L had no mitogenic activity for HD-derived cell lines. In contrast, CD40L enhanced expression of costimulatory molecules intracellular adhesion molecule-T and B7-1 on cultured H-RS cells, both of which are overexpressed on primary H-RS cells. In addition, CD40L induced a 40% to 60% reduction of the expression of the HD-associated CD30 antigen, another member of the TNF receptor superfamily. Primary and cultured H-RS cells express not only CD30, but also CD40. CD40L has pleiotropic biologic activities on H-RS cells, and the CD40-CD40L interaction might be a critical element in the deregulated cytokine network and cell contact-dependent activation cascade typical for HD.

Adult↗
PubMed1994

Road rage.

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Accidents, Traffic↗