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Biomedical subjects

J N Weber

Publications and source records attributed to J N Weber.

At least 73 records · Page 4Linked to original sources
PubMed1994

Infection by HIV-1 blocked by binding of dextrin 2-sulphate to the cell surface of activated human peripheral blood mononuclear cells and cultured T-cells.

1. Structural analogues of a sulphated polysaccharide, dextrin sulphate, were synthesized and tested for their ability to block infection by HIV-1. Using the T-cell lines, C8166 and HPB-ALL, and the laboratory adapted strains of HIV-1.MN, HIV-1.IIIb and HIV-1.RF, dextrin 2-sulphate (D2S) combined the best combination of high anti-HIV-1 activity (95% inhibitory concentration (IC95) = 230 nM) and low anticoagulant activity. It also blocked infection of activated peripheral blood mononuclear (PBMN) cells by five primary viral isolates at an IC95 of 230-3700 nM depending upon the primary viral isolate tested. 2. In saturation binding studies, [3H]-D2S bound to a cell surface protein on HPB-ALL cells in a specific and saturable manner with a Kd of 82 +/- 14 nM and a Bmax of 4.8 +/- 0.3 pmol/10(6) cells. It bound to other human T-cell lines in a similar manner. 3. There was very little binding of [3H]-D2S to freshly isolated PBMN cells (Bmax 0.18 +/- 0.03 pmol/10(6) cells) and these cells could not be infected by HIV-1. Culture of PBMN cells in lymphocyte growth medium (LGM) containing IL-2 did not significantly change the Bmax of [3H]-D2S. In contrast, PBMN cells which had been cultured with phytohaemagglutinin (PHA; 5 micrograms ml-1) for 72 h had a Bmax of [3H]-D2S binding of 7.2 +/- 0.1 pmol/10(6) cells and these cells could be infected by HIV-1. Removal of the PHA and further culture of the PBMN cells in LGM containing IL-2 resulted in a fall in the Bmax to 2.0 +/- 0.1 pmol/10(6) cells. The Kd of binding did not change significantly during the course of these experiments.4. [3H]-D2S did not bind to freshly isolated erythrocytes or to erythrocytes which had been cultured in PHA for 72 h.5. These results suggest that there is a relationship between the expression of the [3H]-D2S binding protein on the plasma membrane of PBMN cells and the susceptibility of these cells to infection by HIV- 1.

Anticoagulants↗
PubMed1994

Molecular epidemiology of HIV-1 in the former Soviet Union: analysis of env V3 sequences and their correlation with epidemiologic data.

OBJECTIVE: To investigate the HIV-1 V3 sequence diversity in the former Soviet Union in 30 subjects infected with HIV-1 via different modes of transmission. PATIENTS: A cohort of children infected after exposure to nonsterile needles during the epidemic in 1988-1989 in southern Russia (Elista, n = 12 and Rostov-on-Don, n = 10), and eight HIV-seropositive subjects from Belarus (Minsk), infected via sexual (n = 7) and parenteral (n = 1) infection. METHODS: The HIV-1 V3 encoding region was amplified by nested polymerase chain reaction on DNA of primary peripheral blood mononuclear cells collected from the study subjects and then cloned and sequenced. RESULTS: The alignment of 127 V3 sequences from 22 patients in the cohort group demonstrated common consensus sequences in both the Elista and Rostov samples. The average means of interperson variation were 5.9 and 6.6% in Elista and Rostov subjects, respectively, and comparable to the mean intraperson variation. The average mean interperson variation between nucleotide sequences of HIV patients infected through sexual transmission was considerably higher (14.9%). CONCLUSION: V3 sequence analysis confirms the epidemiologic data which support the transmission of HIV-1 in children from a single source, and suggests the infection of a mother from her parenterally infected child. Furthermore, the genetic variability of HIV-1 V3 in the noncohort group was particularly divergent indicating the heterogeneity of the virus circulating in the former Soviet Union.

Adolescent↗
PubMed1993

Mycoplasma fermentans in individuals seropositive and seronegative for HIV-1.

Mycoplasmas have been suggested as a co-factor to explain various puzzling features of infection by human immunodeficiency virus 1 (HIV-1). We sought Mycoplasma fermentans by means of a semi-nested polymerase chain reaction (PCR) in samples of peripheral-blood mononuclear cells (PBMC), throat swabs, and urine samples from 117 HIV-seropositive patients (of whom 114 were homosexual men). M fermentans was detected in 12 (10%) PBMC samples, 15 (23%) of 65 throat samples, and 4 (8%) of 55 urine samples from the seropositive subjects. The organism was detected in similar proportions among 73 HIV-seronegative patients recruited from a sexually transmitted diseases clinic (9%, 20%, and 6%, respectively); again, most of the men (40 of 50) in this group were homosexual. We found no association between infection by the mycoplasma and stage of disease, CD4 count, or HIV-1 load. These findings do not, however, eliminate the possibility that the mycoplasmal infection could affect the speed of disease progression.

Blotting, Southern↗
PubMed1993

Identification of human immunodeficiency virus type 1 subtypes and their distribution in the Commonwealth of Independent States (Former Soviet Union) by serologic V3 peptide-binding assays and V3 sequence analysis.

Serologic V3 loop peptide-binding assays have been used to predict divergent human immunodeficiency virus type 1 (HIV-1) strains from the Commonwealth of Independent States (former Soviet Union) that have been subsequently confirmed by sequencing of the V3 region. Initial screening was done by MN V3 peptide binding; 12 parenterally infected HIV-1-positive subjects from Elista and Rostov (group 1) with low-titer MN binding and 6 heterosexually infected HIV-1-positive adults from Byelorussia (group 2) with high-titer MN binding were selected. A consensus sequence from the Elista and Rostov areas was generated; a corresponding 14-mer peptide was synthesized and used in an indirect ELISA to screen sera from 392 individuals from diverse geographic areas. Reactivity to the consensus peptide was 82% in subjects from the homologous areas and 11%-38% in other areas. Antibody binding to a panel of synthetic V3 peptides may be used to predict the presence of diverse strains of HIV-1 within virally heterogenous populations.

Amino Acid Sequence↗
PubMed1993

Variable relationship between proviral DNA load and infectious virus titre in the peripheral blood mononuclear cells of HIV-1-infected individuals.

OBJECTIVES: To determine the relationship between infectious virus titre and proviral copy number in peripheral blood mononuclear cells (PBMC) of infected subjects and to ascertain which, if either, is most closely related to CD4+ cell loss and disease progression. DESIGN AND METHODS: Cellular HIV-1 viraemia was quantified in 45 infected subjects who had not received antiretroviral therapy using limiting dilution tissue culture infective dose (PBMC TCID) and quantitative polymerase chain reaction (PCR) techniques. RESULTS: Proviral DNA was detected in 44 (98%) and infectious virus in 38 (82%) of the 45 subjects. Viraemia as measured by both culture and PCR was inversely correlated with patient CD4+ cell count and associated with disease status. Measurement using both techniques correlated with each other (Spearman's rank correlation rho = 0.52; P = 0.0006). The ratio of proviral copies to PBMC TCID ranged from 1:1 1000:1. to > 1000:1. CONCLUSIONS: The ratio of provirus:PBMC TCID was highest when the PBMC TCID was low, and approached unity when PBMC TCID was high. This ratio could be influenced by a variety of factors but did not correlate significantly with patient disease status or CD4+ cell count.

Base Sequence↗
PubMed1993

Outpatient follow-up in women with HIV infection in Parkside Health Authority (UK).

OBJECTIVE: To describe patterns of attendance for follow-up among HIV infected women in Parkside, UK and their correlates. DESIGN: Retrospective cohort study. SUBJECTS: 103 HIV infected women. MAIN OUTCOME MEASURES: Whether patients attended for follow-up between three and 18 months. RESULTS: 31% of women were married and 46% had children. Women born in sub-Saharan Africa were significantly less likely to attend for follow-up after three months (56%) than women born in other areas who had acquired HIV either heterosexually (82%) or through injecting drug use (81%). This pattern persisted on multivariate analysis controlling for whether women were symptomatic, had had a previous positive test, were married or had children. CONCLUSIONS: HIV positive sub-Saharan African women are less likely to reattend for follow-up than women with heterosexually acquired HIV from other areas or those who acquired infection through intravenous drug use. Further studies are needed to identify barriers to follow-up for women and to shape the development of more appropriate and accessible services for HIV infected women, especially those of sub-Saharan African origin.

Adult↗
PubMed1992

Application of screening and confirmatory assays for anti-HTLV-I/II in U.K. populations.

During an epidemiological study of a low risk U.K. population diverse screening and confirmatory assays for the detection of anti-HTLV-I/II were assessed. Sera from 2,900 antenatal patients were tested for anti-HTLV-I/II by gelatin particle agglutination assay (GPA). All reactive sera, and 133 randomly selected unreactive sera, were further tested by Abbott and DuPont ELISAs, "in house" competitive and IgG capture radioimmunoassays (RIAs), and Western blot (WB). Sera which reacted with any HTLV-I proteins by WB were tested by radio immunoprecipitation assays (RIPA). The two ELISAs detected all the GPA reactive specimens that were subsequently confirmed as anti-HTLV-I/II positive. Confirmation of positive screening results required the use of both WB and RIPA. Serological diagnosis of HTLV infection involves access to specialised assays that are not commercially available.

Agglutination Tests↗
PubMed1992

Investigations into the mechanism by which sulfated polysaccharides inhibit HIV infection in vitro.

Sulfated polysaccharides have been shown to inhibit human immunodeficiency virus (HIV) infection in vitro. Dextrin sulfate, fucoidan, and dextran sulfate fail to neutralize virions directly, but interact with target cells to inhibit virus entry. Ionic interactions of sulfated polyanions with oppositely charged cell surface components, including CD4, have been assumed to be the inhibitory mechanism. It is shown that the sulfated polysaccharides inhibit infection of both CD4+ and CD4- cell lines by HIV and also that they inhibit HTLV-1 and, to a lesser extent, the simian retrovirus, MPMV, which use receptors other than CD4. One binding site for radiolabeled fucoidan on the surface of human T cells is an 18 kD protein, but its significance is not yet clear.

Antiviral Agents↗
PubMed1992

Development of HIV-1 group-specific neutralizing antibodies after seroconversion.

OBJECTIVE: To study the induction of group-specific (gs) neutralizing antibodies to HIV-1 after seroconversion. DESIGN AND METHODS: Serum samples taken sequentially from seven Dutch homosexual men and four British haemophiliacs (anonymous sample, therefore sex not known) before and after seroconversion were tested for neutralizing antibodies effective against five diverse HIV-1 strains. Strains of HIV-1 tested included isolates from the United States, Europe and Africa. RESULTS: The gs neutralizing antibody response varied between individuals. Only five of the 11 individuals studied produced detectable neutralizing antibodies to laboratory-adapted HIV-1 strains (for example, IIIB) within 32 weeks of seroconversion. Most individuals initially produced antibodies effective against US/European isolates; the response then generally broadened to include the more diverse strains, i.e., African. CONCLUSIONS: These results suggest that the gs neutralizing target for HIV-1 is poorly immunogenic in vivo and is probably not highly conserved among diverse HIV-1 strains.

HIV Antibodies↗
PubMed1991

Autoimmune disease and HTLV-1 infection.

We describe two patients who presented with mixed connective tissue disease. Both had antinuclear antibodies and antibodies to the extractable nuclear antigen U1RNP, and both were found to be seropositive for HTLV-1 infection. We found no evidence of HTLV-1 infection in 20 other patients known to have antibodies to U1RNP or in 36 British and West German patients with idiopathic adult polymyositis. In addition the serum from 20 anti-HTLV-1 positive patients did not contain antinuclear antibodies or antibodies to U1RNP. We conclude that rheumatological disease is associated with HTLV-1 through geographical rather than aetiological means.

Adult↗
PubMed1991

Pharmacy drug error awareness program.

Medication errors are a major concern in hospital pharmacy practice. The prevention of medication errors involves mainly the departments of pharmacy and nursing. Though there are many safeguards used to prevent medication errors, they still occur, posing potential harm to patients. To decrease the chance for medication errors to occur pharmacists must take the responsibility to expand their knowledge and teach others about frequent errors. In an effort to decrease medication errors during 1990 at Fresno Community Hospital and Medical Center, Fresno, California, the pharmacy department evaluated the errors made during the calendar year 1989. This evaluation provided information concerning the most frequently occurring medication errors. This information was used to initiate a drug error awareness program (DEAP).

California↗