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Biomedical subjects

N Berry

Publications and source records attributed to N Berry.

At least 37 records · Page 2Linked to original sources

Proviral load and immune function in blood and lymph node during HIV-1 and HIV-2 infection.

Proviral load as well as lymphocyte phenotype and function were compared in peripheral blood and lymph node compartments of 17 HIV-1, 12 HIV-2 and three dually infected patients with lymphadenopathy. The mean percentage (95% confidence interval (CI)) of CD4+ cells was higher in lymph node mononuclear cells (LNMC) than in peripheral blood mononuclear cells (PBMC) in both infections, being 26.7% (21. 1%, 32.3%) and 15.3% (10.4%, 20.2%), respectively, for HIV-1-infected patients (P = 0.0001) and 32.3% (22.7%, 41.9%) and 22. 1% (13.6%, 30.6%), respectively, for HIV-2-infected patients (P = 0. 02). In both types of infection, proviral load adjusted for number of CD4+ cells was higher in LNMC than in PBMC: the geometric mean (95% CI) was 8937 (4991; 16 003) and 4384 (2260; 8503), respectively, for HIV-1 patients (P = 0.02) and 1624 (382; 6898) and 551 (147; 2058) DNA copies, respectively, for HIV-2 patients (P = 0.05). Proviral load in both compartments was closely correlated (HIV-1, r = 0.60, P = 0.01; and HIV-2, r = 0.83, P = 0.0003). In both infections, proliferation and interferon-gamma (IFN-gamma) production in response to purified protein derivative (PPD) was lower in LNMC than in PBMC, both of which, in turn, were lower than in healthy controls. These results indicate that in HIV-2 as in HIV-1 infection, infected cells have a tropism for the lymph nodes resulting in higher viral load in this compartment and lower lymphocyte responses to the recall antigen PPD which may increase susceptibility to tuberculosis.

Adult↗

Evaluation of serological status of rubella & mumps in children below five years.

A cross-sectional study was carried out on 321 serum samples to detect rubella and mumps antibodies in children below five years and to assess the optimum age for immunization against rubella and mumps. Seropositivity to rubella was 33.3 per cent in children below nine months, 16.9 per cent at 9-12 months and 25.5 per cent by two years. Mean antibody levels for rubella were low at nine months to one year and remained so till five years of age. Similarly, seropositivity for mumps was 53.3 per cent below nine months, 20.3 per cent at 9-12 months and 40 per cent by two years. Mean antibody levels for mumps were low between nine months to two years with a slight rise by five years. The findings suggest that a large majority of children are at risk by the age of nine months in our population and the measles, mumps and rubella (MMR) vaccination at this age may be most beneficial.

Antibodies, Viral↗

Association of hepatitis C virus & hepatitis B virus in chronic liver disease.

Hepatitis C virus (HCV) as a cause of chronic liver disease (CLD) was assessed by testing anti-HCV antibodies in the serum samples of 55 patients of chronic hepatitis (17), cirrhosis (32) and hepatocellular carcinoma (6). All the samples were also tested for the presence of HCV RNA by reverse transcription polymerase chain reaction (RT-PCR) using primers from the 5' non-coding region (NCR) and the relationship between the serological parameters and presence of HCV RNA was studied. The association of hepatitis B virus (HBV) with HCV in this group was evaluated by testing for the anti HBc antibodies (IgG and IgM separately) and HBsAg. The biochemical parameters and involvement of other risk factors were also studied. Twenty two (40%) patients were found to be HCV positive and 17 (77.3%) of these had evidence of infection or past exposure to HBV. On comparing the sensitivities of ELISA with that of PCR for the detection of HCV, we observed no significant difference between the two methods (P > 0.05, McNemar's test). Eighteen patients had no evidence of HBV or HCV infection. Our results indicate that HCV is next only to HBV in the causation of CLD. It is suggested that RT-PCR be used with antibody detection by ELISA for reliable detection of HCV infection.

Adult↗

A community-based study of human immunodeficiency virus type 2 provirus load in rural village in West Africa.

A community-based study of provirus load in human immunodeficiency virus (HIV) type 2-infected subjects was done in a rural village in Guinea-Bissau. HIV-2 provirus load varied considerably, with a geometric mean of 124.3 (95% confidence interval, 86.0-179.6) copies/10(5) CD4 cells, which is a level similar to that found in HIV-1 infection. Neither malaria parasitemia, active syphilis, or human T cell leukemia virus coinfection significantly influenced provirus load, nor did age. Eleven of 104 HIV-2-infected subjects had died after 3 years of follow-up; 9 of those who died had a high provirus load of > or = 100 copies/10(5) CD4 cells and a relatively low CD4 cell percentage of < 29%.

Adult↗

Age of wife as a major determinant of male-to-female transmission of HIV-2 infection: a community study from rural West Africa.

OBJECTIVE: To examine whether proviral load is important for transmission between spouses, since we have previously found that the proviral load of HIV-2 predicts the severity of infection. DESIGN: Proviral load was examined in 121 HIV-2-infected adults in a rural area of Guinea-Bissau. For the 68 subjects who had a spouse of known HIV status the risk of the spouse being infected was examined. METHODS: Statistical methods for dependent data were used, because several couples were polygamous. RESULTS: Twenty-seven HIV-2-infected men had 52 current wives of whom 17 (33%) were HIV-2-seropositive. Forty-one HIV-2-infected women had 36 current husbands of known HIV serostatus; nine (25%) were HIV-2-positive. In univariate analyses, concordance of female partners of HIV-2-infected men increased with a previous history of prostitution, age of wife, lack of age difference between the spouses, number of previous husbands, number of wives of the man, and the proviral load. The only significant predictor of concordance in multivariate analyses when wives with a history of prostitution were excluded was an age of 45 years or older [odds ratio (OR), 8.68; 95% confidence interval (CI), 2.34-32.22]. This tendency was not explained by the length of current marriage. Although husbands with a high proviral load were more likely to have concordant spouses than those with a low proviral load (< 20 copies/10(5) CD4 cells), this association was not statistically significant (OR, 2.59; 95% CI, 0.90-7.46). Among spouses of HIV-2-infected women, none of the examined factors, including previous prostitution or proviral load in the woman, predicted whether the husband was HIV-2-infected. CONCLUSIONS: Women appear to be more susceptible to HIV-2 infection after 40-45 years of age. The apparent change in susceptibility may be a major reason for the distinctive age pattern of HIV-2 infection observed in West Africa.

Adolescent↗

HIV-2-specific cytotoxic T-lymphocyte activity is inversely related to proviral load.

OBJECTIVES: To characterize HIV-specific cytotoxic T-lymphocyte (CTL) activities in HIV-2-infected individuals and to relate these to HIV-2 proviral load. METHODS: Peripheral blood mononuclear cells were collected from 16 HIV-2-seropositive and four HIV-1/2 dually seropositive subjects. CTL were restimulated with autologous phytohaemagglutinin-stimulated blasts and CTL activities in 'bulk' cultures were evaluated 7 and 14 days later by a standard 51Cr-release assay using autologous B-cell lines infected with recombinant vaccinia expressing HIV-2 Gag, Pol or Nef protein. Proviral load was quantified by polymerase chain reaction (PCR) which used HIV-2 long terminal repeat primers and an external standard control made by an HIV-2CBL-22 chronically infected C8166 cell line. A biotinylated primer was used to capture the 35S dATP-incorporated secondary PCR product in a quantitative radiometric assay. RESULTS: After 14 days of culture CTL responses against Gag or Pol protein were seen in 18 (90.0%) and 14 (70.0%) out of 20 subjects, respectively, whereas a CTL response was noted against Nef protein in five (25.0%) out of 20 subjects. In 14 (70.0%) out of 20 subjects multiple HIV proteins were simultaneously recognized. The sum of specific lysis (%) against HIV-2 Gag, Pol and Nef at 30:1 effector-to-target ratio, or specific lysis of the dominant CTL response, correlated strongly with HIV-2 proviral load expressed as copies per 10(5) CD4+ cells (r = -0.625, P = 0.003 and r = -0.674, P = 0.001, respectively). CONCLUSION: HIV-2-specific CTL to multiple gene products was demonstrated in most HIV-2-infected individuals. An inverse correlation between the level of CTL activity and proviral load was found, which supports the hypothesis that CTL are important in the control of HIV-2 replication.

Acquired Immunodeficiency Syndrome↗

HIV type 2 proviral load measured by quantitative polymerase chain reaction correlates with CD4+ lymphopenia in HIV type 2-infected individuals.

The efficiency of detection of 2 sets of primer pairs from putatively conserved regions of the human immunodeficiency virus type 2 (HIV-2) genome were assessed in 86 seropositive individuals from The Gambia by nested polymerase chain reaction (PCR). HIV-2 long terminal repeat (LTR) target sequences were detected in DNA extracted from peripheral blood mononuclear cells (PBMCs) in 84 of 86 (97%) individuals whereas HIV-2 integrase (pol) gene sequences were detected in 39 of 41 (95%) individuals. The use of LTR target sequences and recombinant Pfu DNA polymerase, rather than Taq polymerase, in a modified secondary amplification reaction mediated the incorporation of 35S-labeled nucleotides in a quantitative radiometric assay. This sensitive assay was used to quantify HIV-2 proviral DNA in clinical samples and compared well with estimations by limiting end-point dilution of target molecules. A linear response between counts and the number of copies amplified from serial dilutions of pROD10 plasmid DNA (3-2000 copies) yielded a standard curve to allow extrapolation to clinical data. Increased levels of HIV-2 proviral DNA, expressed as copies per 10(5) CD4-positive lymphocytes, were associated with declining CD4 count in 63 adult patients (Spearman rank correlation, r = -0.71, n = 63, p < 0.001) and with the occurrence of HIV-related clinical disease. Kruskall-Wallis analysis of variance analysis showed the mean proviral copy number (log10) to be significantly different between groups (p < 0.001) where CD4 counts were grouped as < 200/mm3 (3.4 +/- 1.05 copies), 200-500/mm3 (2.84 +/- 0.93 copies), and > 500/mm3 (1.88 +/- 0.43 copies).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Competitive EIA for anti-HIV-2 detection in The Gambia: use as a screening assay and to identify possible dual infections.

The performance of a competitive EIA for the detection of HIV-2-specific antibody utilising a viral lysate antigen was assessed over a 3 year period in The Gambia, West Africa, and compared with a commercially available assay, ELAVIA-2, using three panels of sera. An immunodominant region of the transmembrane glycoprotein of an HIV-2 isolate (ANT 53) was also cloned and expressed in E. coli as a beta-galactosidase fusion protein and the resulting recombinant protein substituted in place of the existing viral lysate antigen. Competitive EIAs were found to be both a specific and sensitive means of reliably determining the HIV-2 status of an individual with a high predictive value, particularly when a strategy of concordant positive results in the two EIAs was used. When either anti-HIV-2 competitive EIAs were used in conjunction with a competitive EIA for anti-HIV-1 detection it was possible in the vast majority of cases to identify the virus-type infecting an individual and speciate HIV-1 and HIV-2 infections. A few sera which showed similar regression profiles when diluted over a serial tenfold dilution steps were identified as possible dual infections.

Acquired Immunodeficiency Syndrome↗

Clinical and laboratory predictors of survival in Gambian patients with symptomatic HIV-1 or HIV-2 infection.

OBJECTIVES: To determine which clinical and immunological features of patients with symptomatic HIV-1 and HIV-2 infection best predict survival in The Gambia. METHODS: All patients presenting to two hospitals in The Gambia between January 1987 and June 1990 with symptoms or signs suggesting chronic HIV infection were tested for HIV-1 and HIV-2 antibodies. Eighteen HIV-1 and 31 HIV-2-infected patients were recruited to the study, investigated intensively on admission and followed up until the end of 1990. Presenting clinical features, such as Karnofsky score, diagnosis of AIDS according to World Health Organization Bangui or Centers for Disease Control criteria and number of associated infections, together with five immunological measurements, as well as type of HIV infection, were related to length of survival using proportional hazard models fitted to Kaplan-Meier plots of survival times. RESULTS: Karnofsky score and diagnosis of AIDS were the best clinical predictors of survival. Type of HIV infection or number of associated infections did not predict outcome. The most powerful laboratory predictors were log(e) serum neopterin level, CD4 cell count and log(e) serum beta 2-microglobulin (beta 2M) level. The estimated median survival times (90% confidence interval) of the HIV-1 and HIV-2-infected were six (4-11) and 13 (9-20) months, respectively. These survival times do not differ significantly. CONCLUSIONS: The Karnofsky score and measurements of serum neopterin or beta 2M, which are easier and cheaper to perform than CD4 counts, may prove to be useful guides to prognosis for HIV infection in Africa.

Acquired Immunodeficiency Syndrome↗

Endocytosis of immunotoxin-791T/36-RTA by tumor cells in relation to its cytotoxic action.

Ricin A chain immunotoxin constructed with monoclonal antibody 791T/36, which recognizes a tumor associated glycoprotein Mr 72,000 antigen present on sarcomas and colon and ovarian cancer cells, is cytotoxic for cell lines from tumors expressing this antigen. Incubation of sarcoma 791T cells with immunotoxin for only 5 min is sufficient to produce greater than 95% inhibition of tumor cell growth. Papain treatment of these cells to remove immunotoxin from the cell surface indicated that the cell surface acts as a reservoir for continued internalization of immunotoxin over several hours, but even so, 50% inhibition of cell survival was produced over a 2- to 3-h period. Analysis of the rate of endocytosis demonstrated that 30-50% of cell bound immunotoxin was internalized over a 180-min period. This was primarily dictated by the antibody moiety, regardless of the degree of conjugation to ricin A chain. This rate is much slower than that of other cell surface ligands such as transferrin. Cell cytosol acidification experiments were performed to determine whether this immunotoxin was internalized by clathrin coated pits, which is relatively rapid, or by smooth pits, which is slower, and the results indicated the latter mechanism is almost exclusively used. Intracellular trafficking of antibody 791T/36, conjugated to human serum albumin-tetramethylrhodamine was investigated by flow cytometry. The movement of the conjugate into the lysosomal compartment was delayed so that degradation products were only detected after a lag phase of 30-60 min. The lack of potentiator dependence of 791T/36 immunotoxin is in keeping with these findings.

Ammonium Chloride↗

Risk factors for HIV-2 infection in The Gambia.

A serosurvey was carried out to assess the prevalence of HIV infection in The Gambia and the importance of possible risk factors. The overall prevalence of HIV-2 infection among the 4228 adults studied was 1.7% while that of HIV-1 was 0.1%. The prevalence of HIV-2 was similar in both sexes but higher among those greater than 25 years of age and those who lived in two small towns along a main transport route. Among men, multivariate analysis showed prevalence of HIV-2 infection was significantly greater among those in the more affluent occupations, those without a secondary education and those with a history of urethral discharge. Among women, infection was more frequent in divorcees and widows and those who had been married several times. The prevalence was also higher in individuals born in Guinea-Bissau and in an ethnic group which originated there.

Adolescent↗

Return to work during the year following first myocardial infarction.

This study considers the importance of demographic and psychosocial variables in return to work following a first myocardial infarction. Those patients who returned to work within two months of their infarct, compared with those who had not returned, tended to be younger and of higher socio-economic status. They were also more likely to have an internal locus of control and to have attributed their MI to occupational stressors. Conversely, patients who had not resumed employment one year following their infarction, in comparison with those who had, were likely to be of lower socio-economic status and to have been more depressed immediately following their heart attack.

Follow-Up Studies↗

HIV-2 infection among prostitutes working in The Gambia: association with serological evidence of genital ulcer diseases and with generalized lymphadenopathy.

Three hundred and fifty-five prostitutes working in The Gambia were enrolled in a study of retroviral infections. Eight-seven (24.6%) were infected with HIV-2 only, two (0.6%) with HIV-1 only, four (1.1%) had sera showing double HIV-1/HIV-2 reactivity, and 37 (10.4%) were seropositive for HTLV-I. After allowing for socioeconomic and serological variables in a multivariate analysis, HIV-2 infection was associated with serological evidence of a previous episode of syphilis [a rapid plasma reagin (RPR) positive/Treponema pallidum haemagglutination assay (TPHA) positive; odds ratio (OR) = 2.18, 95% confidence interval (CI) = 1.19-3.98], with having antibodies against Haemophilus ducreyi (OR = 2.05, 95% CI = 0.89-4.70) or against HTLV-I (OR = 2.17, 95% CI = 0.91-5.19). HIV-2-seropositive prostitutes were three times more likely [17 out of 78 (22%) versus 15 out of 219 (7%), P less than 0.001] to have generalized lymphadenopathy than those who were seronegative. These data suggest that genital ulcer diseases may facilitate the transmission of HIV-2, and that HIV-2 rapidly induces the appearance of generalized lymphadenopathy in a substantial proportion of infected individuals.

AIDS-Related Complex↗