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The presence of HIV-1 in latently infected, resting CD[4.sup.+] T cells has been clearly demonstrated in infected individuals; however, the extent of viral expression and the underlying mechanisms of the persistence of HIV-1 in this viral reservoir have not been fully delineated. Here, we show that resting CD[4.sup.+] T cells from the majority of viremic patients are capable of producing cell-free HIV-1 spontaneously ex vivo. The levels of HIV-1 released by resting CD[4.sup.+] T cells were not significantly reduced in the presence of inhibitors of cellular proliferation and viral replication. However, resting CD[4.sup.+] T cells from the majority of aviremic patients failed to produce virions, despite levels of HIV-1 proviral DNA and cell-associated HIV-1 RNA comparable to viremic patients. The DNA microarray analysis demonstrated that a number of genes involving transcription regulation, RNA processing and modification, and protein trafficking and vesicle transport were significantly upregulated in resting CD[4.sup.+] T cells of viremic patients compared to those of aviremic patients. These results suggest that active viral replication has a significant impact on the physiologic state of resting CD[4.sup.+] T cells in infected viremic patients and, in turn, allows release of HIV-1 without exogenous activation stimuli. In addition, given that no quantifiable virions were produced by the latent viral reservoir in the majority of aviremic patients despite the presence of cell-associated HIV-1 RNA, evidence for transcription of HIV-1 RNA in resting CD[4.sup.+] T cells of aviremic patients should not necessarily be taken as direct evidence for ongoing viral replication during effective therapy. HIV | latency | viremia | DNA microarray

Certain HIV-encoded proteins modify host-cell gene expression in a manner that facilitates viral replication. These activities may contribute to low-level viral replication in nonproliferating cells. Through the use of oligonucleotide microarrays and high-through-put Western blotting we demonstrate that one of these proteins, gp120, induces the expression of cytokines, chemokines, kinases, and transcription factors associated with antigen-specific T cell activation in the absence of cellular proliferation. Examination of transcriptional changes induced by gp120 in freshly isolated peripheral blood mononuclear cells and monocyte-derived-macrophages reveals a broad and complex transcriptional program conducive to productive infection with HIV. Observations include the induction of nuclear factor of activated T cells, components of the RNA polymerase II complex including TFII D, proteins localized to the plasma membrane, including several syntaxins, and members of the Rho protein family, including Cdc 42. These observations provide evidence that envelope-mediated signaling contributes to the productive infection of HIV in suboptimally activated T cells.

Paired Ig-like receptors (PIR) that can reciprocally modulate cellular activation have been described in mammals. In the present study, we searched expressed sequence tag databases for PIR relatives to identify chicken expressed sequence tags predictive of [approximately equals] 25% amino acid identity to mouse PIR. Rapid amplification of cDNA ends (RACE)-PCR extension of expressed sequence-tag sequences using chicken splenic cDNA as a template yielded two distinct cDNAs, the sequence analysis of which predicted protein products with related extracellular Ig-like domains. Chicken Ig-like receptor (CHIR)-A was characterized by its transmembrane segment with a positively charged histidine residue and short cytoplasmic tail, thereby identifying CHIR-A as a candidate-activating receptor. Conversely, CHIR-B was characterized by its nonpolar transmembrane segment and cytoplasmic tail with two immunoreceptor tyrosine-based inhibitory motifs, indicating that it may serve as an inhibitory receptor. The use of CHIR amino acid sequences in a search for other PIR relatives led to the recognition of mammalian Fc receptors as distantly related genes. Comparative analyses based on amino acid sequences and three-dimensional protein structures provided molecular evidence for common ancestry of the PIR and Fc receptor gene families.

Objectives: To quantify the risk of infection and disease in spouses of tuberculosis patients and the extent to which intervention could reduce the risk in this highly exposed group.Methods: We compared HIV prevalence, TB prevalence and incidence and tuberculin skin test (TST) results in spouses of TB patients and community controls. HIV-positive spouses were offered isoniazid preventive therapy (IPT), and TST was repeated at 6, 12 and 24 months.Results: We recruited 148 spouses of smear-positive patients ascertained prospectively and 3% had active TB. We identified 203 spouses of previously diagnosed smear-positive patients, 11 had already had TB, and the rate of TB was 2.4 per 100 person years(py) over 2 years (95% CI 1.15-5.09). 116 were found alive and recruited. HIV prevalence was 37% and 39% in the prospective and retrospective spouse groups and 17% in controls. TST was ≥10 mm in 80% of HIV negative and in 57% of HIV-positive spouses ascertained retrospectively; 74% HIV negative and 62% HIV-positive spouses ascertained prospectively, and 48% HIV negative and 26% HIV-positive community controls. Of 54 HIV-positive spouses, 18 completed 6-month IPT. At 2 year follow-up, 87% of surviving spouses had TST ≥10 mm and the rate of TB was 1.1 per 100 py (95% CI 0.34-3.29).Conclusions: Spouses are a high-risk group who should be screened for HIV and active TB. TST prevalence was already high by the time the spouses were approached but further infections were seen to occur. Uptake and adherence to IPT was disappointing, lessening the impact of short-duration therapy. [ABSTRACT FROM AUTHOR]

We describe the development of the HIV epidemic in Karonga District, Malawi over 22 years using data from population surveys and community samples. These data are used to estimate the trend in HIV prevalence, incidence and need for antiretroviral treatment (ART) using a simple mathematical model. HIV prevalence rose quickly in the late 1980s and early 1990s, stabilizing at around 12% in the mid-1990s. Estimated annual HIV incidence rose quickly, peaking in the early 1990s at 2.2% among males and 3.1% among females, and then levelled off at 1.3% among males and 1.1% among females by the late 1990s. Assuming a 2-year eligibility period, both our model and the UNAIDS models predicted 2.1% of adults were in need of ART in 2005. This prediction was sensitive to the assumed eligibility period, ranging from 1.6% to 2.6% if the eligibility period was instead assumed to be 1.5 or 2.5 years, respectively. [ABSTRACT FROM AUTHOR]

Presents a study which investigated variation of surface charge density in monoclonal bacterial populations. Methodology used to conduct study; Measurement of the removal of microorganisms from suspension due to attachment to the surfaces of the solid phase; Function of colloid filtration theory in study; Implications of the study's findings.

Editor's Note. This article presents the remarks, in 1988, of an expert panel on the negotiation of a joint venture between the General Motors Corporation and Toyota Motor Corporation during 1982-84. The negotiations between these two multinational corporations, one American and one Japanese, shed light on the process of negotiation in the world arena. Stephen E.Weiss, a specialist in negotiation and conflict management and a former member of the faculty of the New York University Stern School of Business, presents the broad outlines of the setting for the joint venture. Mark T. Hogan, who became General Manager of General Affairs and Comptroller for New United Motor Manufacturing, Inc. (NUMMI), the joint company formed by General Motors and Toyota, suggests key factors that serve to sustain the joint venture. Jay W. Chai, a Korean-born American who was the number-two man in General Motors' negotiating team, offers perceptions and insights from his experience. Eugene J. Meigher, a member of the American law firm representing Toyota throughout the planning stages and negotiations, comments on his workings with Toyota to respond to requests for information from the Federal Trade Commission (FTC). Edward F. Glynn, Jr., presents the FTC's interest in reviewing the proposed venture. Last, Dennis Cuneo, vice president for legal and governmental affairs of NUMMI, considers the reasons for success of the venture and the different negotiating styles of the Americans and Japanese involved. The NUMMI plant in Fremont, California, is a meeting place for two cultures. Japanese managers have had to learn to depend on American workers, who differ fundamentally from their Japanese counterparts, but who have learned to work according to the team concept pioneered by the Japanese. Likewise, Japanese managers working at the Fremont plant are learning to relax and take a break once in a while. The negotiations that led to this joint venture were also a meeting of two cultures and tw... [ABSTRACT FROM PUBLISHER]

Focuses on the issuance of the exposure draft to delay the application of Statement 96 of the Financial Accounting Standards Boards which centers on the accounting of income tax in the U.S. Consideration of the aggregate method to reduce the complexity of the statement with the reduction of scheduling and tax-planning strategy; Possibility of the implementation of the incremental method to change the criteria for recording deferred tax assets with consideration of earning future income; Combination of aggregate and incremental methods.

Presents the text of a speech given by Edward F. Glynn Jr., member of the District of Columbia Bar, on August 7, 1990 which deals on the subject of product distribution law in Chicago, Illinois.

Comments on the American enforcement perspective on the merger regulation of the European Union countries. Volatility of the criteria of the legal systems; Revolution of the system around elasticity of supply and demand; Awareness of the government and private counsel on the basic criterion in raising the prices of relevant goods.

Presents the text of the speech given by Edward F. Glynn Jr, official of the U.S. Federal Trade Commission, during the 37th Annual Meeting of the American Bar Association Section of Antitrust Law on August 6–9, 1989 in Honolulu, Hawaii, regarding international joint ventures.

Background: We aimed to assess whether interferon-γ release assays (IGRAs) can predict the development of active tuberculosis and whether the predictive ability of these tests is better than that of the tuberculin skin test (TST).Methods: Longitudinal studies of the predictive value for active tuberculosis of in-house or commercial IGRAs were identified through searches of PubMed, Embase, Biosis, and Web of Science and complementary manual searches up to June 30, 2011. Eligible studies included adults or children, with or without HIV, who were free of active tuberculosis at study baseline. We summarised incidence rates in forest plots and pooled data with random-effects models when appropriate. We calculated incidence rate ratios (IRR) for rates of disease progression in IGRA-positive versus IGRA-negative individuals.Findings: 15 studies had a combined sample size of 26 680 participants. Incidence of tuberculosis during a median follow-up of 4 years (IQR 2-6), even in IGRA-positive individuals, was 4-48 cases per 1000 person-years. Seven studies with no possibility of incorporation bias and reporting baseline stratification on the basis of IGRA results showed a moderate association between positive results and subsequent tuberculosis (pooled unadjusted IRR 2·10, 95% CI 1·42-3·08). Compared with test-negative results, IGRA-positive and TST-positive results were much the same with regard to the risk of tuberculosis (pooled IRR in the five studies that used both was 2·11 [95% CI 1·29-3·46] for IGRA vs 1·60 [0·94-2·72] for TST at the 10 mm cutoff). However, the proportion of IGRA-positive individuals in seven of 11 studies that assessed both IGRAs and TST was generally lower than TST-positive individuals.Interpretation: Neither IGRAs nor the TST have high accuracy for the prediction of active tuberculosis, although use of IGRAs in some populations might reduce the number of people considered for preventive treatment. Until more predictive biomarkers are identified, existing tests for latent tuberculosis infection should be chosen on the basis of relative specificity in different populations, logistics, cost, and patients' preferences rather than on predictive ability alone.Funding: Special Programme for Research and Training in Tropical Diseases (WHO), Wellcome Trust, Canadian Institutes of Health Research, UK Medical Research Council, and the European and Developing Countries Clinical Trials Partnership. [ABSTRACT FROM AUTHOR]

Objective: To estimate the impact of cotrimoxazole prophylaxis on the survival of human immunodeficiency virus (HIV)-positive tuberculosis (TB) patients. Methods A cohort study with a historical comparison group was conducted. End-of-treatment outcomes and 18-month survival were compared between TB patients registered in 1999 and patients registered in 2000 Karonga District, Malawi. Case ascertainment, treatment and outpatient follow-up were identical in the two years except that in 2000 cotrimoxazole prophylaxis was offered to HIV-positive patients in addition to routine care. The prophylaxis was provided from the time a patient was identified as HIV-positive patients in addition to routine care. The prophylaxis was provided from the time a patient was identified as HIV-positive until 12 months after registration. Analyses were carried out on an intention-to-treat basis for all TB patients, and also separately by HIV status, after registration of diagnosis. Findings 355 and 362 TB patients were registered in 1999 and 2000, respectively; 70% were HIV-positive. The overall case fatality rate fell from 37% to 29%, i.e. for every 12.5 TB patients treated, one death was averted. Case fatality rates were unchanged between the two years in HIV-negative patients, but fell in HIV-positive patients from 43% to 24%. The improve survival became apparent after the first 2 months and was maintained beyond the end of treatment. The improvement was most marked in patients with smear-positive TB and others with confirmed TB diagnoses. Conclusion Survival of HIV-positive TB patients improved dramatically with the addition of cotrimoxazole prophylaxis to the treatment regimen. The improvement can be attributed to cotrimoxazole because other factors were unchanged and the survival of HIV-negative patients was not improved. Cotrimoxazole prophylaxis should therefore be added to the routine care of HIV-positive TB patients. [ABSTRACT FROM AUTHOR]