Impaired T cell immunity in B cell-deficient mice following viral central nervous system infection.

CD8(+) T cells are required to control acute viral replication in the CNS following infection with neurotropic coronavirus. By contrast, studies in B cell-deficient (muMT) mice revealed Abs as key effectors in suppressing virus recrudescence. The apparent loss of initial T cell-mediated immune control in the absence of B cells was investigated by comparing T cell populations in CNS mononuclear cells from infected muMT and wild-type mice. Following viral recrudescence in muMT mice, total CD8(+) T cell numbers were similar to those of wild-type mice that had cleared infectious virus; however, virus-specific T cells were reduced at least 3-fold by class I tetramer and IFN-gamma ELISPOT analysis. Although overall T cell recruitment into the CNS of muMT mice was not impaired, discrepancies in frequencies of virus-specific CD8(+) T cells were most severe during acute infection. Impaired ex vivo cytolytic activity of muMT CNS mononuclear cells, concomitant with reduced frequencies, implicated IFN-gamma as the primary anti viral factor early in infection. Reduced virus-specific CD8(+) T cell responses in the CNS coincided with poor peripheral expansion and diminished CD4(+) T cell help. Thus, in addition to the lack of Ab, limited CD8(+) and CD4(+) T cell responses in muMT mice contribute to the ultimate loss of control of CNS infection. Using a model of virus infection restricted to the CNS, the results provide novel evidence for a role of B cells in regulating T cell expansion and differentiation into effector cells.

Creating a physician compact that drives group success.

A physician compact is the unwritten understanding of what an organization and its employees owe one another. When expectations clash about job security, salary, hours and the like, the practice--and its patients--suffer. Outdated expectations of the physician compact can hamper an organization from functioning smoothly and delivering optimal care. Rewriting a compact should involve all of a group's physicians, and should be endorsed and promoted by practice leadership. A satisfactory compact develops a shared sense of strategic imperatives and helps a practice reach its potential.

Decision Support Systems (DSS) in fracture treatment.

Systems for analysis and verification of final treatment results (outcomes) play articular role in medical sciences. Data collected by Decision Support Systems (DSS) allows the making of multivariable analysis and optimalized clinical decision. The options of applying the Decision Support Systems (DSS) in orthopaedics traumatology based on fracture treatment with special interest in fracture diagnostics and healing monitoring are described. The paper explains value of operational systems, central database, sort of data collected, analytical tools and data delivery system. Authors also emphasize telemedicine approach to DSS of fracture treatment.

How can IDSs integrate conflicting cultures?

Many integrated delivery systems (IDSs) perform poorly because of cultural differences of their constituents. To reconcile such differences and start to develop one unifying culture, IDSs need to promote a set of cultural values and expectations that support the entire enterprise. Creating a unified, functional culture is a complex process that ranges from identifying the organization's strategic aims and assessing current cultures in light of those aims, to being courageous and consistent in demonstrating the organization's values.

Evidence against the exon theory of genes derived from the triose-phosphate isomerase gene.

The exon theory of genes proposes that the introns of protein-encoding nuclear genes are remnants of the DNA spacers between ancient minigenes. The discovery of an intron at a predicted position in the triose-phosphate isomerase (EC 5.3.1.1) gene of Culex mosquitoes has been hailed as an evidential pillar of the theory. We have found that that intron is also present in Aedes mosquitoes, which are closely related to Culex, but not in the phylogenetically more distant Anopheles, nor in the fly Calliphora vicina, nor in the moth Spodoptera littoralis. The presence of this intron in Culex and Aedes is parsimoniously explained as the result of an insertion in a recent common ancestor of these two species rather than as the remnant of an ancient intron. The absence of the intron in 19 species of very diverse organisms requires at least 10 independent evolutionary losses in order to be consistent with the exon theory.

The HMO physician as team player.

For HMOs to function most effectively, physicians and support staff need to work together as teams. Successful teamwork requires a high degree of communication and coordination, attributes that are often lacking unless the HMO has decentralized authority and nurtures effective teamwork. This article describes barriers that impede teamwork, and focuses on specific steps that can be taken to enhance the team environment in a prepaid group practice.

Function of the LFA-1 and T4 molecules in the direct activation of resting human B lymphocytes by T lymphocytes.

Activated T lymphocytes can provide all of the signals necessary to induce the proliferation of resting B lymphocytes. The activation signal is presumably initiated through direct T-B lymphocyte contact. The role of the leukocyte function antigen-1 (LFA-1) and T4 molecules in the activation of purified, small B lymphocytes by mitomycin C-treated T lymphocytes was examined by using monoclonal antibodies that react with and inhibit the function of these molecules. Anti-LFA-1 antibody binding significantly inhibited T-B lymphocyte interactions that result in B lymphocyte proliferation. In contrast, the presence of anti-T4 antibodies at concentrations as high as 100 micrograms/ml did not inhibit this interaction. These results indicate that the B lymphocyte activation signal may not be mediated through the interaction of T4 molecules with major histocompatibility complex class II antigens of the B lymphocyte but is a cell-cell contact-dependent event that is facilitated by LFA-1 molecules.

Expression of the common acute lymphoblastic leukemia antigen (CALLA) on the surface of individual cells of human lymphoblastoid lines.

Expression of the common acute lymphoblastic leukemia antigen (CALLA) on the surface of individual cells of the human lymphoblastoid lines CW678, Namalwa, and Nalm-6, and the distribution of the antigen epitopes within the cell populations have been determined quantitatively with the murine monoclonal anti-CALLA antibody J5. The distribution of CALLA epitopes in the cell populations was analyzed by indirect immunofluorescence measured by using flow cytometry. The average number of CALLA epitopes per cell were measured by two assays: in a direct assay by binding 125I-labeled antibody J5 to cells, and indirectly by binding 125I-labeled protein A from Staphylococcus aureus to J5-coated cells. On average, CW678, Namalwa, and Nalm-6 cells bore about 1 X 10(4), 6 X 10(4), and 8 X 10(4) CALLA epitopes per cell respectively. Histograms of the absolute number of CALLA epitopes expressed by individual cells in the populations of CW678, Namalwa, and Nalm-6 cultures were generated by a combined analysis of all the binding data. This is the first example of histograms showing quantitative distribution of antigen epitopes. Previously, the expression of antigens by individual cells as obtained by flow cytometry was only presented in terms of relative fluorescence intensity of individual cells in cell populations.

Differential expression of HLA-DR antigens in subsets of human CFU-GM.

Expression of HLA-DR surface antigens by granulocyte/monocyte colony-forming cells (CFU-GM) may be important in the regulation of proliferation of these cells. Using immunological techniques to enrich for progenitor cells, we investigated the expression of HLA-DR in subsets of CFU-GM. "Early" (day 14) CFU-GM express higher levels of HLA-DR than do "late" (day 7) CFU-GM. Among late CFU-GM, cells destined to form monocyte (alpha-naphthyl acetate esterase-positive) colonies express higher levels of HLA-DR than do CFU-GM destined to form granulocyte (chloroacetate esterase-positive) colonies. Because high-level expression of DR antigen was a marker for monocyte differentiation, we examined several lymphokines for their effects on both DR expression and in vitro commitment to monocyte differentiation by myeloid precursor cells. DR antigen density could be increased by more than twofold over 48 hours upon exposure to gamma-interferon (gamma-IFN), whereas colony-stimulating factors had no effect. This was associated with a dose-dependent inhibition of total CFU-GM number, and a relative, but not absolute, increase in the ratio of monocyte colonies to granulocyte colonies. Similarly, in day 7 suspension cultures of purified myeloid precursor cells, gamma-IFN inhibited cell proliferation and increased the ratio of monocytes to granulocytes. Thus, despite the induction of high levels of HLA-DR antigen on precursor cells (a marker of monocyte commitment), the dominant in vitro effect of gamma-IFN was inhibition of granulocyte differentiation.

The isolation and characterization of the human helper inducer T cell subset.

Monoclonal antibody anti-4B4 was produced by fusing NS1 myeloma with spleen cells of a mouse immunized with Saguinus oedipus lymphocyte. This anti-4B4 antibody defines a 135-KD cell surface protein that is widely distributed throughout the hematopoietic system. More importantly, anti-4B4 is reactive with functionally unique human T cell subsets. Anti-4B4 antibody was reactive with approximately 41% of unfractionated T cells, 41% of T4+ inducer cells, and approximately 43% of T8+ cytotoxic/suppressor population. This antibody subdivided peripheral blood T4+ cells into two functionally distinct populations. The T4+4B4+ subset proliferates relatively poorly upon stimulation with Con A and autologous cell antigens (AMLR) but well on exposure to soluble antigens, and it provides a good helper signal for PWM-induced Ig synthesis. The T4+4B4- subset, in contrast, proliferates well to Con A stimulation and autologous cell antigen (AMLR) but relatively poorly to soluble antigen stimulation, and provides little help to B cells for PWM-induced Ig synthesis. The T4+4B4- subset is largely 2H4+ and functions as the inducer of the T8+ suppressor cells. Thus, the present results suggest that one can divide the human T4 population into two major subsets that are phenotypically and functionally distinct, the human helper inducer subset (T4+4B4+/H.I.) and its reciprocal population defined by anti-2H4, the suppressor inducer subset (T4+2H4+/S.I.).

Acceptance of preventive measures by individuals, institutions and communities.

The acceptance by individuals, institutions and communities of preventive measures for controlling the two most prevalent dental diseases, dental caries and periodontal disease, is limited. A wide gap exists between available preventive methods and their appropriate application. Adoption of preventive dental self-care (tooth brushing, flossing diet modification) is organized around five categories of determinants influencing oral health behaviours: psychological factors; face-to-face interactions between people; broad societal influences; information and the immediate surroundings; and reinforcement schemes. While each of these five categories of determinants influences adoption of the desired behaviours, altering any single factor does not usually result in sustained behaviour change. Institutions (e.g. schools and workplaces) and communities are sites where the determinants of individual behaviours can be altered and preventive services can be delivered. Very little research has been conducted to improve our understanding of the variables which explain why dental health prevention programmes are accepted or rejected by institutions or communities. When programmes are adopted, little is known about the accuracy of their administration or about barriers to, and problems in, their implementation and maintenance. To achieve optimal oral health throughout life, a combination of passive measures (e.g. water fluoridation, school-based fluoride programmes) and active personal behaviours (e.g. oral hygiene, diet control) is required. Therefore, it is essential that researchers and practitioners improve their understanding of the acceptance of passive measures by institutions and communities as well as their understanding of the adoption of active measures by individuals.

Planning the educational component of a hypertension control program: a case study.

The failure to plan the health education component of a health service program together with the total planning effort has severely limited the contribution education could make to program goals. This case study illustrates the use of the systematic observation of behavior to identify factors which facilitated or hindered the development of a hypertension control program in ambulatory facilities and boards of health. The relationship of these factors to the planning process is discussed. Although this project deals with hypertension, the factors identified as facilitating or hindering change are applicable to any public health program.