Withdrawal of funding for intercalating BSc students.
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Biomedical subjects
Publications and source records attributed to R Boyd.
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CD4 and CD8 gene-deleted New Zealand black (NZB) mice and, as controls, B6.CD4 -/-, B6.CD8 -/-, NZB, and B6 wild-type (wt) mice were studied for phenotypic and immunologic parameters to determine the contribution of CD4 and CD8 cell lineages in NZB mice. These studies suggest surprisingly that a number of abnormalities are not due to either CD4+ or CD8+ cell lineages but rather are most likely due to non-CD4+ and -CD8+ cell lineages and/or background genes. Such abnormalities include altered thymic architecture, decreased staining of MITS 33+ medullary thymocytes, and an increased frequency of splenic IgM secretory cells. In contrast, deletion of either CD4+ or CD8+ cells appears to differentially influence immunologic function. Deletion of CD8+ cells did not influence titers of spontaneously occurring anti-erythrocyte or anti-DNA autoantibodies. interestingly, 50% of NZB.CD4 -/- mice contained levels of anti-erythrocyte IgG and anti-ssDNA IgM autoantibodies; even without detectable CD4+ cells. Such deletion of CD4+ cells, while leading to marked decreases in the prototype cytokines that characterize Th1 and Th2 subsets in B6 mice, led to a marked increase in IFN-gamma and a moderate increase in IL-4 mRNA levels in NZB.CD4 -/- mice. These data suggest that whereas non-CD4+ and -CD8+ cell lineages and NZB background genes have a marked influence in the development of autoimmune abnormalities, CD4+ cells appear to play a major role in influencing the cytokine environment, whereas CD8+ cells appear to play a minor role.
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BACKGROUND: There is little consensus regarding the most efficient or the safest method by which to place a central venous catheter (CVC). METHODS: A single house officer prospectively evaluated 140 patients for whom he was requested to place CVCs. One hundred and eight patients participated in a randomized study of positioning. Of the 140 patients, 7 had emergency line placement; 105 randomized patients undergoing elective CVC placement form the basis for this report (power > 80% to detect change of one needle pass between groups). Patient positions were termed "bump" (head turned to the contralateral side and a rolled towel placed vertically between the scapulas) and "no bump" (head facing forward and no towel placed in the back.) RESULTS: Ninety-three of 105 patients had successful catheter placement. Catheters were more often successfully introduced in the bump group than no bump group (98% versus 83%, P < 0.04). For patients with difficult CVC placement (those > 160 pounds, those with a weight-to-height ratio > 29, those with previous unsuccessful catheterization), the bump position was superior with respect to increased likelihood of venous blood return, decreased likelihood of arterial blood return, and increased likelihood of successful catheterization, although differences did not reach statistical significance (P < 0.05) in individual analyses. Of patients with successful catheterization, 97% had three or fewer needle passes. Those with more than three needle passes were less likely to have successful catheter placement (P < 0.01), were more likely to have arterial blood return (P < 0.01) and pneumothorax (P = 0.12). CONCLUSIONS: The bump position improves the likelihood of successful central venous catheter placement. No more than three needle passes ought to be attempted.
OBJECTIVE: (1) To determine the accuracy of accident and emergency (A&E) doctors' diagnosis of radio-opaque ureteric calculi on plain abdominal radiographs; (2) to study the predictive value of haematuria with a history suggestive of ureteric colic. DESIGN: A prospective study of all patients seen in a three month period with a provisional diagnosis of ureteric colic. Intravenous urography (IVU) was used as the gold standard for diagnosis of ureteric calculi. SETTING: The accident and emergency department and medical unit of a large teaching hospital. SUBJECTS: 60 patients who were admitted with an initial diagnosis of ureteric colic, 51 subsequently undergoing intravenous urography. RESULTS: A&E doctors achieved a calculated sensitivity of 29% (95% confidence intervals 13% to 49%) and a specificity of 73% (52% to 90%) for identification of renal calculi on plain abdominal radiograph, compared with figures of 68% (48% to 84%) and 96% (78% to 100%) respectively for consultant radiologists. The difference between these results was highly significant (P = 0.0011). No patient with a definitive diagnosis of ureteric colic had a negative result for haematuria on urinary dipstick analysis. CONCLUSIONS: A&E doctors are poor at identifying radio-opaque ureteric calculi on plain abdominal radiographs. If haematuria is absent on urinalysis then ureteric colic is an unlikely diagnosis.
Immunosenescence has been well described in both human and a variety of animal species and has an important influence on changes in immune function. Although several mechanisms may be operating to explain the alterations in immune function with age, one factor that has attracted significant attention has been the progressive age-dependent involution of the thymus. Hitherto, most studies of thymus have focused only on thymocytes. We have now taken advantage of a well-defined panel of monoclonal antibodies (mAbs called MTS) that recognize and characterize the thymic miroenvironment, including epithelial and nonepithelial elements. Recent data using these MTS mAbs have disclosed significant abnormalities in the thymic cortex in models of murine lupus including the unusual appearance of medullary-type epithelial cells in the cortical areas and the presence of epithelial free spaces or 'cortical holes'. In this study, we investigated age-related changes in the thymic microenvironment in 12-month-old C3H/HeJ, C57BL/6 and BALB/c mice. Controls included thymus from young 4-to 6-week-old mice as well as 6-month-old BALB/c mice. As expected, the thymus of all 12-month-old mice manifested normal and distinctive separation of cortical and medullary epithelium. However, unlike younger mice, the 12-month-old mice had severe changes in these regions. For example, in older mice, the cortex and medulla were diffusely irregular and atrophic and had a poorly defined cortico medullary junction; the former having small disrupted epithelial networks, and the latter containing clusters of atrophic cells. Moreover, the extracellular matrix was increased and contained large irregularly shaped clusters. Interestingly, the thymus of 6-month-old mice expressed some changes within the medullary epithelium and the extracellular matrix, but the cortical epithelium remained unchanged. These age-related degenerative changes in the thymic microenvironment differ significantly from the abnormalities identified in autoimmunity and may be a factor in immunosenescence.
Efforts to define the stromal architecture of thymic tissues of normal mice have used a panel of monoclonal antibodies (MTS series) to examine the localization of cell subtypes, including reagents that define thymic epithelial and stromal elements. Recent work with these MTS mAbs disclosed significant abnormalities in the thymic cortex of New Zealand mice including the appearance of medullary type epithelial cells in the cortical areas and the presence of epithelial free spaces or 'cortical holes'. To determine whether such abnormalities are unique to NZB mice or are found in other models of murine lupus, we examined the thymi of MRL/MP-lpr/lpr BXSB/MpJ Yaa, C3H/HeJ-gld/gld and C57BL/6 control mice. Thymi from all models of murine lupus showed dramatic alterations in the thymic microarchitecture. For example, staining with MTS10, a mAb which is specific for subcapsular and medullary epithelia, was decreased in the subcapsular and medullary regions. Moreover, there was increased staining in the thymic cortex, suggesting an abnormality in the localization of MTS10-reactive cells. Moreover, all three murine lupus strains demonstrated 'cortical holes' or cortical epithelial cell-free regions. By using MTS33, MTS35 and flow cytometry, both C3H/gld and BXSB/Yaa, but not MRL/lpr mice, showed decreased cortical thymocyte frequencies. Possible defects in the maturation of double-positive thymocytes to single-positive status in C3H/gld mice is implied by abnormally high levels of double-positive cells and low levels of single-positive cells. Finally, MRL/lpr thymocytes had lowered frequencies of CD3-4+8+ and increased levels of TCR-alpha/beta high cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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1-2% of adult mouse thymocytes express the T cell receptor alpha/beta (TCR-alpha/beta) together with the interleukin (IL) 2R beta (p70), but not the alpha (p 55) chain. We show that the previously described alpha/beta-TCR +CD4-8- and the partially overlapping Ly6C+ thymocytes are contained within this subset. Most IL-2R beta+ alpha/beta-TCR+ cells have a mature and activated (heat stable antigen [HSA]-, thymic shared antigen 1 [TSA-1]-, CD44high, CD69+) phenotype. Overrepresentation of V beta 8.2 in both CD4-8- and CD4 and/or CD8+ IL-2R beta+ thymocytes suggests that IL-2R beta expression is induced by a TCR-mediated activation event. In mice transgenic for an H-2Kb-specific TCR, IL-2R beta+ cells were abundant under conditions of mainstream negative selection, i.e., in the presence of Kb, but absent under conditions of mainstream positive selection or in a nonselecting environment. Together, these results show that in addition to clonal deletion, self-recognition by immature thymocytes leads to phenotypic maturation of a small subset of thymocytes expressing IL-2R beta. IL-2-deficient mice contain normal numbers of IL-2R beta+ alpha/beta-TCR+ thymocytes, indicating that like mainstream T cell development, this minor pathway of positive selection does not depend on IL-2. However, in the absence of IL-2, the CD4/CD8 subset composition of IL-2R beta+ thymocytes is skewed towards CD4-8+, mostly at the expense of CD4-8-. A possible relevance of this finding for the development of the immune pathology of IL-2-deficient mice is discussed.
Deaf history is more complex and ambiguous than previous studies have indicated, and historians' preoccupation with the manual-oral controversy has precluded a full understanding of deaf people's lives. The historical interests and organized efforts of the Pennsylvania Society for the Advancement of the Deaf (PSAD) transcended language issues and focused on balancing the risks and the benefits of deaf self-determination. One hundred years ago, PSAD's leaders concentrated their efforts on philanthropy and lobbying for the general good of deaf Pennsylvanians, while remaining silent on controversies over deaf education. In effect, they accepted oralism and hearing hegemony in education in exchange for deaf autonomy and improvement in other areas of life. If the PSAD's experience is typical of other state organizations, simple historical models that focus on the actions of hearing oppressors obscure the actual creativity, struggles, and sophistication of America's deaf leaders.
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We have taken advantage of an extensive panel of mAb directed to thymic epithelial and nonepithelial stromal cells to examine the expression of these Ag from day 16 of gestation through 6 mo of age in NZB(H-2d), NZB.H-2b, NZB.H-2bm12, C57BL/6(H-2b), and C57BL/6.H-2bm12 mice. In addition, by triple color flow cytometry we have examined the expression of cell surface markers defining distinct stages of intrathymic T cell maturation. New Zealand mice demonstrated three abnormalities. MTS 10 normally stains thymic medullary and subcapsular epithelium. However, New Zealand mice demonstrated striking irregular medullary epithelial cell shape whereas their subcapsular epithelium remained normal. Moreover, New Zealand mice, unlike controls, were found to have MTS 10+ epithelial cells within the cortex. Additionally, MTS 39 and MTS 44, which normally stain reticular cortical epithelium, produced a striking different staining pattern in New Zealand mouse thymus, including the presence of large cortical epithelial cellfree regions, so-called "cortical holes." MTS 33 normally stains cortical thymocytes but in New Zealand mice, there was a severe decrease of MTS 33+ cells. There was also an increase of CD3lowCD4+CD8+ cells in NZB mice, which may include many predeletion thymocytes. Finally, there was a significant increase of CD3highCD4+CD8- cells in NZB.H-2bm12 and C57BL/6.H-2bm12 mice compared with NZB.H-2b and C57BL/6(H-2b) mice. We postulate that these microenvironmental alterations in NZB mice contribute to and reflect altered T cell differentiation, thereby predisposing them to autoimmune disease. Moreover, the increased proportion of CD3highCD4+CD8- cells associated with the H-2bm12 mutation may be involved in the remarkably different profiles of disease between NZB.H-2b and NZB.H-2bm12 mice.
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The sensitivity of radiolabeled bile acid (BA) binding and transport by basal plasma membrane (BPM) vesicles of human trophoblast to cholephilic organic anions (COAs) was studied by a rapid filtration technique. Glycocholate (GC) efflux from preloaded (15 microM GC) vesicles was investigated in the presence of 300 microM COAs at the trans-side of the membrane. Bilirubin (BR) diglucuronide and rose bengal induced a very strong transstimulating effect, whereas phalloidin and phenol red showed a negligible effect. This effect was from strong to moderate for indocyanine green > bromosulfophthalein (BSP) > or = fusidic acid > or = phenolphthalein > or = BR ditaurate > or = rifamycin SV > or = rifampicin. BSP-induced transstimulation was not additive to the "velocity effect" previously reported for bicarbonate. At the cis-side, BSP reduced the saturable component of taurocholate (TC) binding to BPM vesicles. BSP also induced a partial and mixed type of inhibition both in TC uptake [inhibitor constant (Ki) 227 microM] and efflux (Ki 209 microM). Two binding sites with overlapping specificity for BAs and other COAs are proposed in this carrier, the site for non-BA COA presumably corresponding to that for bicarbonate. In summary, the results indicate that several COAs can act as potential substrates for the BA carrier located at the BPM of human trophoblast. This stresses the "biliary-like" role of the placenta and suggests the possibility of developing new functional tests for this organ on the basis of fetal-maternal transfer of nontoxic cholephilic dyes.
An outbreak of foodborne gastroenteritis affected 648 United States Air Force personnel stationed in Jeddah, Saudi Arabia during Operation Desert Storm. The implicated food source was a locally catered meal. Despite the presence of an aggressive Air Force public health program, foodborne illness had a major impact on manpower and medical resources during a critical phase of military operations. It is the recommendation of the authors that the Air Force not rely on local caterers during future deployments.