Biomedical subjects

A Talal

Publications and source records attributed to A Talal.

9 recordsLinked to original sources

PubMed2004

Neutralizing antibody response during acute and chronic hepatitis C virus infection.

Little is known about the role of Abs in determining the outcome of hepatitis C virus (HCV) infection. By using infectious retroviral pseudotypes bearing HCV glycoproteins, we measured neutralizing Ab (nAb) responses during acute and chronic HCV infection. In seven acutely infected health care workers, only two developed a nAb response that failed to associate with viral clearance. In contrast, the majority of chronically infected patients had nAbs. To determine the kinetics of strain-specific and crossreactive nAb emergence, we studied patient H, the source of the prototype genotype 1a H77 HCV strain. An early weak nAb response, specific for the autologous virus, was detected at seroconversion. However, neutralization of heterologous viruses was detected only between 33 and 111 weeks of infection. We also examined the development of nAbs in 10 chimpanzees infected with H77 clonal virus. No nAb responses were detected in three animals that cleared virus, whereas strain-specific nAbs were detected in six of the seven chronically infected animals after approximately 50 weeks of infection. The delayed appearance of high titer crossreactive nAbs in chronically infected patients suggests that selective mechanism(s) may operate to prevent the appearance of these Abs during acute infection. The long-term persistence of these nAbs in chronically infected patients may regulate viral replication.

Acute Disease↗

PubMed2001

Open-label phase II trial of amprenavir, abacavir, and fixed-dose zidovudine/lamivudine in newly and chronically HIV-1--infected patients.

A Phase II clinical trial was designed to evaluate the efficacy and tolerability of twice-daily abacavir, amprenavir, and zidovudine (ZDV)/lamivudine (3TC) in HIV-1-infected study subjects naive to protease inhibitors and 3TC. Plasma and cerebrospinal fluid (CSF) HIV-1 RNA levels and T-cell subsets were measured. In all, 27 newly diagnosed and 12 chronically HIV-1-infected study subjects are included in the analysis. Week 48 plasma HIV-1 RNA levels were <500 copies/ml in 100% of study subjects, and <50 copies/ml in 80% of chronically infected and 100% of newly infected study subjects. The mean change in CD4 was (+)150 cells/microl (newly infected, p <.001), and (+)155 cells/microl (chronically infected, p <.001). At Week 48, evidence of cellular activation persisted in both cohorts. A twice-daily regimen of amprenavir, abacavir, and ZDV/3TC affords potent viral suppression and significant increases in total CD4(+) cells in HIV-1--infected study subjects. Patient intolerance may limit the efficacy of this combination.

AIDS Dementia Complex↗

PubMed1999

Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy.

BACKGROUND: In patients infected with human immunodeficiency virus type 1 (HIV-1), combination antiretroviral therapy can result in sustained suppression of plasma levels of the virus. However, replication-competent virus can still be recovered from latently infected resting memory CD4 lymphocytes; this finding raises serious doubts about whether antiviral treatment can eradicate HIV-1. METHODS: We looked for evidence of residual HIV-1 replication in eight patients who began treatment soon after infection and in whom plasma levels of HIV-1 RNA were undetectable after two to three years of antiretroviral therapy. We examined whether there had been changes over time in HIV-1 proviral sequences in peripheral-blood mononuclear cells, which would indicate residual viral replication. We also performed in situ hybridization studies on tissues from one patient to identify cells actively expressing HIV-1 RNA. We estimated the rate of decrease of latent, replication-competent HIV-1 in resting CD4 lymphocytes on the basis of the decrease in the numbers of proviral sequences identified during primary infection and direct sequential measurements of the size of the latent reservoir. RESULTS: Six of the eight patients had no significant variations in proviral sequences during treatment. However, in two patients there was sequence evolution but no evidence of drug-resistant viral genotypes. In one patient, extensive in situ studies provided additional evidence of persistent viral replication in lymphoid tissues. Using two independent approaches, we estimated that the half-life of the latent, replication-competent virus in resting CD4 lymphocytes was approximately six months. CONCLUSIONS: These findings suggest that combination antiretroviral regimens suppress HIV-1 replication in some but not all patients. Given the half-life of latently infected CD4 lymphocytes of about six months, it may require many years of effective antiretroviral treatment to eliminate this reservoir of HIV-1.

Adult↗

PubMed1999

Genomic diversity of "Norwalk like viruses" (NLVs): pediatric infections in a Brazilian shantytown.

"Norwalk-like viruses" (NLVs) are a common cause of epidemic gastroenteritis in adults and children in developed countries. However, little is known about the role of NLVs in endemic pediatric gastroenteritis in developing countries. We sequenced Genogroup I and II NLV reverse transcription-polymerase chain reaction (RT-PCR) products from an 81-nucleotide region of the viral RNA polymerase gene to examine the molecular epidemiology of NLV infection in children younger than 5 years of age in Forteleza, Ceará, Brazil. NLV-positive PCR products were obtained from stool specimens collected over a 16-month period (1990-1991) from diarrhea cases and controls in a cohort of 120 children in an urban shantytown and from a study in the same city of hospitalized children with persistent diarrhea. Eight unique strains were detected in 15 specimens from 10 cohort children and in two hospital specimens. Nucleotide identity between the strains (5 Genogroup I, 3 Genogroup II) ranged from 63% to 88%. We designated these strains BraV1-8, for Brazil virus 1-8. The degree of genomic diversity of NLV strains we identified in this cohort during a short time period suggests multiple foci of infection within the community. Furthermore, sequence analysis of strains from two children with multiple symptomatic NLV infections indicates that infection with one strain was not protective against subsequent infection with a different strain in the same genogroup. These findings have implications for vaccine development and the prevention of pediatric gastroenteritis in developing countries.

Brazil↗

PubMed1999

The effect of commencing combination antiretroviral therapy soon after human immunodeficiency virus type 1 infection on viral replication and antiviral immune responses.

Twelve subjects were treated with zidovudine, lamivudine, and ritonavir within 90 days of onset of symptoms of acute infection to determine whether human immunodeficiency virus type 1 (HIV-1) infection could be eradicated from an infected host. In adherent subjects, with or without modifications due to intolerance, viral replication was suppressed during the 24-month treatment period. Durable suppression reduced levels of HIV-1-specific antibodies and cytotoxic T lymphocyte responses in selected subjects. Proviral DNA in mononuclear cells uniformly persisted. The persistence of HIV-1 RNA expression in lymphoid tissues and peripheral blood mononuclear cells suggests that elimination of this residual pool of virus should be achieved before considering adjustments in antiretroviral therapeutic regimens. In addition, given the reduction in levels of virus-specific immune responses, it would seem prudent to consider enhancing these responses using vaccine strategies prior to the withdrawal of antiviral therapy.

Acquired Immunodeficiency Syndrome↗

PubMed1998

In vivo distribution of the human immunodeficiency virus/simian immunodeficiency virus coreceptors: CXCR4, CCR3, and CCR5.

We have evaluated the in vivo distribution of the major human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) coreceptors, CXCR4, CCR3, and CCR5, in both rhesus macaques and humans. T lymphocytes and macrophages in both lymphoid and nonlymphoid tissues are the major cell populations expressing HIV/SIV coreceptors, reaffirming that these cells are the major targets of HIV/SIV infection in vivo. In lymphoid tissues such as the lymph node and the thymus, approximately 1 to 10% of the T lymphocytes and macrophages are coreceptor positive. However, coreceptor expression was not detected on follicular dendritic cells (FDC) in lymph nodes, suggesting that the ability of FDC to trap extracellular virions is unlikely to be mediated by a coreceptor-specific mechanism. In the thymus, a large number of immature and mature T lymphocytes express CXCR4, which may render these cells susceptible to infection by syncytium-inducing viral variants that use this coreceptor for entry. In addition, various degrees of coreceptor expression are found among different tissues and also among different cells within the same tissues. Coreceptor-positive cells are more frequently identified in the colon than in the rectum and more frequently identified in the cervix than in the vagina, suggesting that the expression levels of coreceptors are differentially regulated at different anatomic sites. Furthermore, extremely high levels of CXCR4 and CCR3 expression are found on the neurons from both the central and peripheral nervous systems. These findings may be helpful in understanding certain aspects of HIV and SIV pathogenesis and transmission.

Animals↗

PubMed1995

Rational approach to small polyps found on sigmoidoscopy.

Most colorectal cancers are thought to develop from benign adenomas. Because adenomas are found in a large proportion of asymptomatic individuals, most adenomas must remain benign. Current guidelines suggest that colonoscopy is not necessary when hyperplastic polyps are found at screening sigmoidoscopy. Existing data suggest that small adenomatous polyps may also not be associated with substantial risk of current or future malignancy. We suggest that small polyps seen on flexible sigmoidoscopy require neither biopsy nor subsequent colonoscopy. Such an approach requires further study, but could result in substantial cost savings, with modest risk to patients.

Adenomatous Polyps↗

PubMed1995

Evaluating risk: a primer for gastroenterologists.

OBJECTIVE: To review the various types of risk measures and to illustrate how interpretations may vary depending on how risk is presented. METHODS: We define different types of risk estimates and provide examples of their use from the recent gastroenterological literature. RESULTS: Calculations of absolute risk and the number of patients who must receive treatment to prevent one patient from experiencing a disease state (number needed to treat) provide useful information in assessing the utility of fecal occult blood testing for prevention of colorectal cancer and in estimating small bowel cancer rates for individuals with familial adenomatous polyposis. CONCLUSIONS: Measures such as relative risk and the odds ratio are best used in analyzing causality but may not be helpful in guiding clinical decisions. Absolute risk and attributable risk reveal the actual number of cases that can be explained by a given exposure and can thereby measure the impact of a clinical intervention for both the population and the patient. These measures should be the criteria for decision-making.

Adenomatous Polyposis Coli↗

PubMed1990

Raynaud's phenomenon in primary Sjögren's syndrome.

Our study describes the prevalence, clinical picture, course and sequelae of Raynaud's phenomenon in patients with primary Sjögren's syndrome. Furthermore, our study compares the clinical, serologic and immunogenetic profile of patients with Raynaud's phenomenon versus those without Raynaud's phenomenon. It seems that Raynaud's phenomenon is a common manifestation (33%) in patients with primary Sjögren's syndrome, precedes sicca manifestations in 42% of patients and follows a pleomorphic course; in some patients (14%) it disappears during the course of Sjögren's syndrome, in others (30%) the frequency of attacks decreases while in a 3rd group (56%) it remains the same. The local clinical sequelae of Raynaud's phenomenon in patients with primary Sjögren's syndrome are swollen hands and evidence of small, soft tissue calcifications on radiographs. Digital pulp ulcers, sclerodactyly or periungal telengiectases are not seen. It seems however, that patients with primary Sjögren's syndrome and Raynaud's phenomenon develop glomerulonephritis, myositis and peripheral neuropathy more often than patients without Raynaud's phenomenon. These differences however, had no statistical significance. Finally, the autoantibody profile is similar in patients with and without Raynaud's phenomenon, while patients without Raynaud's phenomenon and primary Sjögren's syndrome showed a negative but not statistically significant association with the HLA-DR4 alloantigen.

HLA-DR4 Antigen↗