PubMed Health⌕ Search

Biomedical subjects

J G Wong

Publications and source records attributed to J G Wong.

At least 19 recordsLinked to original sources
PubMed1997

TCR-independent CD28-mediated gene expression in peripheral blood lymphocytes from donors chronically infected with HIV-1.

Complete activation of peripheral blood T cells requires both T-cell receptor (TCR) stimulation and CD28 costimulation. Signalling pathways associated specifically with CD28 are not well understood, however, because ligation of CD28 in the absence of TCR stimulation does not give rise to cellular responses in normal cells. In peripheral blood lymphocytes (PBL) from donors chronically infected with human immunodeficiency virus-1 (HIV-1), CD28 can induce viral replication through an alternative pathway that does not require TCR ligation. We have exploited this observation to study CD28-mediated signal transduction using reverse transcriptase-mediated polymerase chain reaction (RT-PCR) to amplify viral RNA. Independent ligation of CD28 on donor PBL induced expression of the HIV-1 tat gene but not the interleukin-2 (IL-2) gene. Viral induction did not occur following pretreatment of cells with actinomycin D, suggesting it was mediated through transcriptional activation of the viral long terminal repeat (LTR). tat was induced in the presence of the protein kinase C inhibitor H-7, but was inhibited by cyclosporin A. Our results demonstrate that CD28 is linked directly to specific signalling pathways leading to de novo induction of genes in PBL.

CD28 Antigens↗
PubMed1997

To screen or not to screen for HIV in pregnant women. Pros and cons of routine screening and use of home test kits.

Emotions run high when it comes to who should and who should not be tested for HIV. Now, as the debate heats up over screening of all pregnant women and their babies, primary care physicians may find themselves caught in the fray. Recent approval of home HIV test kits allows patients to test themselves, but can the results be trusted? Dr. Wong summarizes the contentious issues, looks at the debate from both sides, provides supportive documentation when available, and points out the "knowledge gaps."

Diagnostic Tests, Routine↗
PubMed1996

IL-7 up-regulates HIV-1 replication in naturally infected peripheral blood mononuclear cells.

We have investigated the effect of exogenous IL-7 on replication of HIV-1 in PBMCs isolated from asymptomatic, chronically infected donors. We show that IL-7 induced virus replication and increased proviral DNA levels in CD8- PBMC cultures. IL-7 also increased the levels of doubly spliced HIV-1 tat RNA in these cultures. In comparison, IL-2 induced lower levels of virus production than IL-7, but had a more pronounced effect on cell proliferation. The IL-7-mediated increase in virus replication was not inhibited by neutralizing mAbs to IL-1 beta, IL-2, IL-6, or TNF-alpha, and was only partially dependent on ligation of the T cell accessory molecule CD28. CD8+ cells inhibited the increase in viral replication following IL-7 stimulation, but did not prevent virus replication following ligation of CD3 in the presence of IL-7. The data shows that IL-7 regulates HIV-1 replication in naturally infected PBMCs.

Antiviral Agents↗
PubMed1996

Kainic acid-induced focal cortical seizure is associated with an increase of synaptophysin immunoreactivity in the cortex.

Aberrant neural sprouting of mossy fiber terminals in the supragranular layer of dentate gyrus is consistently observed following seizures in an animal model of epilepsy. It is also observed in hippocampi taken from epileptic patients with hippocampal sclerosis. The aberrant neural sprouting with synaptic reorganization is one of the proposed cellular mechanisms underlying epileptogenesis. It is not known whether aberrant synaptogenesis can be induced in the cortex, as in hippocampus, by seizure activity. In this study, synaptic terminals in the cortex were measured after focal cortical seizures by a semiquantitative image analysis of synaptophysin immunoreactivity. Brief intracortical perfusion of kainic acid induced focal status epilepticus and destructive cortical lesions. Synaptophysin immunoreactivity was significantly increased in the area where kainic acid was perfused. The increase of synaptophysin immunoreactivity, indicating an increase of synaptogenesis, was observed at 2 and 4 weeks after focal cortical seizures. This result suggests that kainic acid-induced seizure activity is associated with long-lasting synaptogenesis in the cortex. Studies centering on the physiological consequences of aberrant synaptogenesis may lead to additional understanding of the mechanisms underlying cortical epileptogenesis.

Animals↗
PubMed1996

Efficiency and effectiveness in the urgent care clinic.

Events at an urgent care clinic are unpredictable. On a given day, a practitioner may be challenged, bored, frustrated, and excited by patients and the problems they bring for evaluation. The setting offers a concentrated learning environment to sharpen clinical skills because of the many patients with various medical problems seen in a relatively short period. Keys to success in urgent care are organized evaluation of every patient and vigilance to the opportunity to intervene and make a significant difference in patient outcome.

Clinical Competence↗
PubMed1995

Human immunodeficiency virus type 1 infection of CD4+ T cells down-regulates the expression of CD28: effect on T cell activation and cytokine production.

Infection with human immunodeficiency virus type 1 (HIV-1) results in dysregulation of normal T cell function. To study the effects of HIV-1 at the cellular level, primary T cell lines were generated by alloantigen stimulation of CD4+ T cells collected from peripheral blood of HIV-1-infected donors. Using Epstein-Barr virus-infected B lymphocytes (EBV-LCL) as a source of alloantigen, the T cell lines were expanded in vitro for 7 weeks. Uninfected T cell lines were cultured in parallel. Virus was inducible from the infected lines with stimulation, and complete infection was achieved after 4-7 weeks depending on the line. The down-modulation of CD28 expression correlated with virus replication and spread. Furthermore, CD28 mRNA was not inducible in the infected lines after stimulation with alloantigen. Loss of CD28 correlated with reduced responsiveness to costimulation with a monoclonal antibody to CD28 following similar engagement of the CD3 protein. In contrast, activation with alloantigen was not affected. HIV-1 infection and down-modulation of CD28 did not alter the relative levels of IL-2, IFN-gamma, and IL-4 mRNA. Production of the various cytokine mRNAs following alloantigen stimulation was inhibited by CTLA4Ig and thus remained under the regulation of CD80 and CD86 expressed on the EBV-LCL. Taken together, our data suggest that dysregulation of normal T cell function associated with HIV-1 infection may result in part form the loss of CD28 expression.

CD28 Antigens↗
PubMed1995

Costimulation of CD4+ T cells via CD28 modulates human immunodeficiency virus type 1 infection and replication in vitro.

Stimulation of human immunodeficiency virus type 1 (HIV-1)-infected donor peripheral blood mononuclear cells (PBMCs) via the TCR-CD3 complex induces HIV-1 production in vitro (Zarling JM, et al.: Nature [London] 1990;347:92; Haffar OK, et al.: J Virol 1992;66:4279; Moran PM, et al.: AIDS Res Hum Retroviruses 1993;9:455). However, in addition to the primary stimulatory signal delivered through the TCR-CD3 complex, optimal T cell activation requires secondary or costimulatory signals delivered via various T cell accessory proteins (Alton A, et al.: Adv Immunol 1990;48:227). In this article we explore the role of costimulation of T cells via CD28 in HIV-1 replication. Ligation of CD28 with either a CD28-specific MAb or by coculture of PBMCs with Chinese hamster ovary (CHO) cell lines stably expressing either of the CD28 counterreceptors, B7-1 (CD80) or B7-2 (CD86), concomitant with stimulation via CD3, results in increased virus replication compared to stimulation via CD3 alone. CD28 ligation also augments de novo infection of CD3-stimulated seronegative donor PBMCs with cell-free virus. Increased virus replication following CD28 ligation is not solely attributed to increased levels of endogenous IL-2, because addition of an anti-IL-2-neutralizing antibody only partially inhibits the response. In contrast, interfering with the interaction between CD28 and its counterreceptors on antigen-presenting cells (APCs) using CTLA4Ig effectively inhibits virus replication. At high concentrations CTLA4Ig also reduces cell proliferation. These in vitro results suggest that CD28 plays a central role in HIV-1 replication and that interfering with the CD28 costimulatory pathway may modify the course of HIV-1 infection.

Animals↗
PubMed1994

Drug-induced meningitis. A case involving trimethoprim-sulfamethoxazole.

Drug-induced meningitis should be considered in differential diagnosis of meningeal irritation in patients receiving therapy with anti-infective, nonsteroidal anti-inflammatory, immunosuppressive, or other selected agents. This report describes a case of aseptic meningitis associated with use of trimethoprim-sulfamethoxazole in a patient without apparent underlying autoimmune disease. The patient recovered promptly after the offending agent was withdrawn. No specific treatment other than symptomatic and supportive care need be given. In all instances, however, infection must be excluded.

Adult↗
PubMed1994

A triggered mechanism retrieves membrane in seconds after Ca(2+)-stimulated exocytosis in single pituitary cells.

In neuroendocrine cells, cytosolic Ca2+ triggers exocytosis in tens of milliseconds, yet known pathways of endocytic membrane retrieval take minutes. To test for faster retrieval mechanisms, we have triggered short bursts of exocytosis by flash photolysis of caged Ca2+, and have tracked subsequent retrieval by measuring the plasma membrane capacitance. We find that a limited amount of membrane can be retrieved with a time constant of 4 s at 21-26 degrees C, and that this occurs partially via structures larger than coated vesicles. This novel mechanism may be arrested at a late step. Incomplete retrieval structures then remain on the cell surface for minutes until the consequences of a renewed increase in cytosolic [Ca2+] disconnect them from the cell surface in < 1 s. Our results provide evidence for a rapid, triggered membrane retrieval pathway in excitable cells.

Animals↗
PubMed1994

Impact of intensive lipid modulation on angiographically defined coronary disease: clinical implications.

We reviewed all randomized, controlled angiographic trials to assess the impact of intensive lipid modulation on the progression or regression of angiographically defined coronary disease. Five of seven trials satisfied selection criteria: Cholesterol-Lowering Atherosclerosis Study, Program on the Surgical Control of the Hyperlipidemias, Familial Atherosclerosis Treatment Study, Regression of Coronary Atherosclerosis During Treatment of Familial Hypercholesterolemia, and St. Thomas' Atherosclerosis Regression Study. We compared patient selection, baseline and on-trial lipid values, changes in angiographic disease scores, and clinical outcomes. In all five trials, treatment reduced levels of low-density lipoprotein (LDL) cholesterol substantially (range -32% to -46%). Treatment reduced risk of angiographic progression by almost 50% compared to controls. Furthermore, nearly one third of drug-treated patients showed angiographic regression of disease. Regression correlated well with reduction in LDL cholesterol. Although overall improvement in stenosis was modest, reduction in clinical events was impressive. Intensive lipid modulation may "stabilize" existing lesions, making them less "active" (ie, less prone to rupture or thrombosis), thereby reducing risk of acute coronary syndromes. These studies clearly support intensive lipid modulation in patients with established coronary disease.

Angiography↗