Predictive value of prior Rose angina for myocardial infarction confirmation after emergency admissions.

The Rose Questionnaire, developed to facilitate screening for the presence of coronary artery disease, has shown good utility for white men and more variable utility among Latino, African-American, and female subjects. This study investigated its utility for prediction of outcome in patients with suspected myocardial infarction. A total of 1428 white, Latino, and African-American subjects completed questionnaires after emergency admission, which were correlated with diagnoses at the time of discharge from a public hospital and private hospital. Results indicated that subjects with positive questionnaires were less likely to have infarction confirmed at discharge, except for those with a prior history of myocardial infarction, than those with a negative response. These data are important in evaluating the overall utility of the Rose Questionnaire and the significance of angina.     

Genetic Variation of the Borrelia burgdorferi Gene vlsE Involves Cassette-Specific, Segmental Gene Conversion

The Lyme disease spirochete Borrelia burgdorferi possesses 15 silent vls cassettes and a vls expression site (vlsE) encoding a surface-exposed lipoprotein. Segments of the silent vls cassettes have been shown to recombine with the vlsE cassette region in the mammalian host, resulting in combinatorial antigenic variation. Despite promiscuous recombination within the vlsE cassette region, the 5′ and 3′ coding sequences of vlsE that flank the cassette region are not subject to sequence variation during these recombination events. The segments of the silent vls cassettes recombine in the vlsE cassette region through a unidirectional process such that the sequence and organization of the silent vls loci are not affected. As a result of recombination, the previously expressed segments are replaced by incoming segments and apparently degraded. These results provide evidence for a gene conversion mechanism in VlsE antigenic variation.     

Enhancement of macrophage microbicidal activity: supplemental arginine and citrulline augment nitric oxide production in murine peritoneal macrophages and promote intracellular killing of Trypanosoma cruzi.

The generation of nitric oxide (NO) is largely responsible for the intracellular killing of Trypanosoma cruzi by activated macrophages. The present study was carried out to determine whether the production of NO by activated murine macrophages cultured in physiologic levels of arginine can be augmented by increasing the availability of arginine, the substrate for NO biosynthesis. Increased exogenous arginine or citrulline resulted in a significant increase in NO production and complete clearance of the parasites by activated macrophages. As citrulline fully substituted for arginine in supporting NO production and trypanocidal activity, these results demonstrate the expression of a highly active citrulline-NO cycle in activated macrophages and that levels of arginine in plasma are limiting with respect to both NO production and trypanocidal activity in these cells. The results indicate that increasing plasma substrate levels for both arginine and NO biosynthesis may represent a means of enhancing microbicidal activity in vivo.     

Interleukin-6 production by astrocytes: Induction by the neurotransmitter norepinephrine

Astrocytes contribute to the immunocompetence of the central nervous system (CNS) via their expression of class II major histocompatibility complex (MHC) antigens and the production of inflammatory cytokines such as interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Of these cytokines, IL-6 is of particular interest because one of its many immune and inflammatory actions is the promotion of immunoglobulin synthesis, and it is thought that IL-6 expression within the brain exacerbates autoimmune diseases of the CNS, which are marked by local immunoglobulin production. Several stimuli induce astrocyte IL-6 expression, including such inducible endogenous factors as IL-1β and TNF-α. We have investigated the possibility that a constitutively present endogenous factor, the neurotransmitter norepinephrine (NE), can induce astrocyte IL-6 production. We report that NE induces both IL-6 mRNA and protein in primary neonatal rat astrocytes, with optimal induction at 10 μM. IL-6 protein induction by NE is comparable to that seen with IL-1β or TNF-α, and NE synergizes with these cytokines for a ten-fold enhanced effect. In contrast to astrocytes, microglia are relatively unresponsive to NE, IL-1β and TNF-α for IL-6 production. Experiments with the β-adrenergic receptor agonist isoproterenol, and α and β-adrenergic receptor antagonists (propranolol, phentolamine, atenolol, and yohimbine) indicate that β₂ and α₁-adrenergic receptors are involved in NE induction of astrocyte IL-6 expression. These results help to further the understanding of neuron-glial interactions, and the role of astrocytes and adrenergic activity in immune responses within the CNS.     

Basilar artery blood flow in subclavian steal

Subclavian "steal", when blood siphons from one vertebral artery to the other, has been suggested as a cause of brain stem ischaemia and stroke. We investigated 33 patients using transcranial Doppler to determine the direction and velocity of basilar blood flow. All patients had severe subclavian stenosis with reversed vertebral blood flow in the ipsilateral artery previously demonstrated by extracranial Doppler. Basilar flow was normal in direction in all cases, but its velocity was significantly increased (p less than 0.0008) compared to age- and sex-matched controls. These findings, in conjunction with previous observations using extracranial Doppler techniques, suggest that subclavian steal is little more than a harmless haemodynamic phenomenon.     

Primary Health Care through a community based smoking-cessation program

The International Conference on Primary Health Care, meeting in Alma-Ata, in the Soviet Union, September 12, 1978, expressed the need for urgent action by all governments, all health and development workers and the world community, to protect and promote the health of all people of the world. The world was caught by the phrase which emerged from this conference, Health For All by the Year 2000 and many have examined the articles of the Alma-Ata declaration and tried to implement them in their corner of the world. This paper describes a community-based smoking-cessation program which was implemented in the province of Nova Scotia, Canada, during the years 1980–1984. Primary to this project was the belief that people have the right and the duty to participate individually and collectively in planning and implementing their health care. This paper describes one community's effort in putting this belief into practice.Carol Smillie, B.N. BE.d. M.S.c. is an Assistant Professor at the School of Nursing, Dalhousie University, Halifax, Nova Scotia, Canada B3H 3J5, Katherine Coffin, BA, MEd is the Program Officer, Nova Scotia Office, Health Promotion Directorate Health and Welfare Canada, 5251 Duke Street, Halifax, Nova Scotia. Canada B3J 1P3. Kathryn Porter, B.A. (Gen)., is the Information and Education Coordinator, Nova Scotia Division Canadian Cancer Society. Brenda Ryan, B.A., M.B.A. is Program Evaluation Analysist, Nova Scotia Department of Health, 6088 Hollis Street, Halifax. Nova Scotia, Canada. This Project was funded by Health and Welfare Canada, Nova Scotia Department of Health, Nova Scotia Division Canadian Cancer Society, Requests for reprints should be addressed to: Professor Carol Smillie.     

Decreased infectivity despite unaltered C3 binding by a DeltahbhA mutant of Mycobacterium tuberculosis

HbhA of Mycobacterium tuberculosis is a multifunctional binding protein, binding to both sulfated sugars such as heparin and to human complement component C3. HbhA may therefore interact with host molecules and/or host cells during M. tuberculosis infection and play a role in the pathogenesis of this bacterium. The purpose of this study was to use allelic exchange to create an M. tuberculosis strain deficient in expression of HbhA to determine whether this protein's C3-binding activity plays a role in the pathogenesis of M. tuberculosis. An in-frame, 576-bp unmarked deletion in the hbhA gene was created using sacB as a counterselectable marker. Southern blotting and PCR analyses confirmed deletion of hbhA in the DeltahbhA mutant. The DeltahbhA mutant strain grew at a rate similar to that of the parent in broth culture and in J774.A1 murine macrophage-like cells but was deficient in growth compared to the parent strain in the lungs, liver, and spleen of infected mice. In addition, the DeltahbhA mutation did not reduce binding of M. tuberculosis to human C3 or to J774.A1 cells in the presence or absence of serum, suggesting that in the absence of HbhA, other molecules serve as C3-binding molecules on the M. tuberculosis surface. Taken together, these data indicate that HbhA is important in the infectivity of M. tuberculosis, but its ability to bind C3 is not required for mycobacterial adherence to macrophage-like cells. Using the DeltahbhA mutant strain, a second M. tuberculosis C3-binding protein similar in size to HbhA was identified as HupB, but the role of HupB as a C3-binding protein in intact organisms remains to be determined.