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Biomedical subjects

A E Brown

Publications and source records attributed to A E Brown.

At least 37 records · Page 2Linked to original sources
PubMed2001

HIV viral load in Thai men and women with subtype E infections.

The assessment of potential "breakthrough infections" in HIV vaccine trials requires knowledge of viral load in unvaccinated persons. Therefore, HIV-1 RNA was quantitated in plasma from Thai adults with subtype E infections. RNA was detectable (> or =500 copies/ml) in 93% of 255 specimens, with a mean (standard deviation) value of 4.09 (0.88) log copies/ml. The concentration of RNA was directly related to the presence of AIDS-defining illnesses, inversely related to CD4 count, and independent of gender after adjustment for CD4 count.

AIDS Vaccines↗
PubMed2001

Detection and quantification of HIV type 1 RNA in nasopharyngeal washes from HIV-infected subjects.

Human immunodeficiency virus type 1 (HIV) RNA load was measured in paired samples of peripheral blood plasma and nasopharyngeal (NP) washes from 97 Thai subjects infected with subtype E or B. HIV RNA was quantifiable in 93% of peripheral blood plasma samples tested and was inversely correlated (rho =-0.524; p < 0.001) with CD4 absolute count. HIV RNA was quantifiable in 29% of NP samples tested, and the median value was less than that of plasma viral load. HIV RNA load in NP samples was correlated (rho = 0.388; p < 0.001) with viral load in peripheral blood. HIV RNA was not detected in NP washes from subjects with undetectable plasma viral load. Virus isolation attempts on two NP samples were negative. The results do not support local HIV production in the nasopharynx, but extend current knowledge of HIV shedding to include the NP compartment.

CD4 Lymphocyte Count↗
PubMed2001

HIV type 1 subtype E-infected patients with broadened, dual (B/E) V3 loop serology have increased cross-neutralizing antibodies.

The two prevalent subtypes of HIV-1 circulating in Thailand are subtypes E and B. While the most prevalent subtype continues to be E using molecular typing assays, immunologically, a subset of subtype E-infected patients (3.4% in 1997) have binding antibodies to both the E and B V3 loops in a peptide ELISA. To assess the potential function of this dual (B/E) V3 reactivity, plasmas from patients with genetically defined HIV-1 subtype E infection and either E or B/E V3 serotypes were compared for magnitude and breadth of neutralization of seven primary and laboratory-adapted subtype B and E viruses. Dually reactive (B/E) plasmas showed significantly increased cross-neutralizing activity against subtype B viruses (p < 0.001), and increased neutralization of the panel of viruses overall (p < 0.02), as compared to monoreactive E serotype plasmas. While the total envelope binding antibody titers to both subtype B and E envelopes did not differ significantly between the E and B/E plasmas, 67% of B/E plasmas neutralized >50% of the viruses in the panel, and only 14% of E plasmas showed this broadened neutralizing activity. These data suggest that dual (B/E) V3 loop reactivity may be a marker of broader immune recognition of HIV envelope epitopes in subtype E-infected patients. V3 loop antibody, perhaps in conjunction with antibodies to additional epitopes, may play a role in neutralization of virus isolates from Thailand.

Amino Acid Sequence↗
PubMed2001

Suprafascial dissection of the radial forearm flap and donor site morbidity.

A cutaneous free radial forearm flap was harvested from 25 patients using a suprafascial dissection technique. The donor site was managed with either a full or split thickness skin graft and a negative pressure wound dressing. The incidence of initial complete graft take was 96% at day 5 and 100% by 1 month. There was 100% early and complete graft take in the full thickness group but one area of partial loss in the split thickness group. This area of graft loss represented less than 0.5% of the total grafted area in this series. The mean time to wound healing was 14 days. There were no cases of tendon exposure or delayed healing. The suprafascial dissection creates a superior graft recipient bed. When combined with the negative pressure wound dressing technique it ensured early and complete graft take.

Adult↗
PubMed2001

Clinical prognosis of patients with early-stage human immunodeficiency virus (HIV) disease: contribution of HIV-1 RNA and T lymphocyte subset quantitation.

Systems for the staging of individuals with human immunodeficiency virus type 1 (HIV-1) infection were developed 15 years ago. Subsequently, assays for quantitating HIV-1 RNA and immunophenotyping of lymphocyte subsets have been developed and validated. The utility of these assays for improved staging in early disease was evaluated in 256 HIV-infected adults (52% minority) with CD4 counts > or = 400 cells/microL followed in U.S. military medical centers before the highly active anti-retroviral therapy era. HIV viral load (RNA) was quantitated; the frequencies of select CD4+ immunophenotypes were determined in 112 subjects. The results were analyzed in relation to three outcome measures: death, first acquired immunodeficiency syndrome-defining opportunistic infection, and CD4 count < or = 200 cells/microL. Serum RNA level and CD4 count were each found to be predictive of all three outcomes. In addition, increases in the T-cell subsets CD28-CD4+ and CD29+CD26-CD4+ were found to be independently predictive of more rapid progression. The classification of early-stage HIV patients is improved by the quantitation of both viral RNA and T-lymphocyte subsets.

Adult↗
PubMed2001

Evaluation of a new fourth-generation microwell enzyme-linked immunosorbent assay for detection of HIV-1 subtype B and E antibodies.

The recent fourth-generation enzyme-immunoassays have been used to increase the sensitivity for detecting HIV-1 antibodies and reduce the window period of HIV infection. The HIV antigens utilized in those assays were prepared from HIV-1 clade B which is different from HIV-1 subtypes circulating in Thailand. We evaluated 323 HIV-1 seropositives either B or E subtype to determine whether they were detected with the new combined anti-HIV and the p24 Ag assay. Under evaluation we found that this enzyme immunoassay manufactured by Organon Teknika showed the high sensitivity and specificity with a greater delta (delta) value with B than E subtypes samples (+15.29 vs +5.73).

Amino Acid Sequence↗
PubMed2000

HIV-1 suppression during acute scrub-typhus infection.

BACKGROUND: In HIV-1-infected individuals, viral load has been reported to rise transiently if an acute infection with another organism occurs. Our study was prompted by the unexpected finding that HIV-1 copy number fell during an acute infection with Orientia tsutsugamushi, the causative agent of scrub typhus. METHODS: Serial HIV-1 viral load determinations were made in ten Thai adults with scrub typhus, who were not receiving antiretroviral therapy, and in five HIV-1-infected patients who had other infections (four malaria, one leptospirosis), during and after acute infections. Sera from HIV-1-infected patients with scrub typhus and from mice immunised with O. tsutsugamushi were examined for HIV-1-suppressive activity. FINDINGS: Median viral load 3 days after admission was significantly lower in the scrub-typhus group than in patients with other infections (193% vs 376% of day 28 values, p=0.03). In four O. tsutsugamushi-infected patients HIV-1 RNA copy number fell by three-fold or more compared with day 28 values, and HIV-1 copy numbers were below the assay threshold in two patients with scrub typhus. Five of seven HIV-1 isolates from non-typhus patients with CD4 lymphocytes less than 200 cells/microL were syncytia-inducing variants, whereas all ten isolates from O. tsutsugamushi-infected individuals matched by CD4-cell count were non-syncytia inducing (p=0.03). Sera from an HIV-1-negative patient with scrub typhus had potent HIV-1-suppressive activity in vitro. Sera from typhus-infected mice inhibited HIV-1 syncytia formation and bound by immunofluorescence to HIV-1-infected lymphocytes. INTERPRETATION: HIV-1-suppressive factors are produced during some scrub-typhus infection and should be investigated further in the search for novel strategies for the treatment and prevention of AIDS.

Acute Disease↗
PubMed2000

A comparative study of the impact of HIV infection on natural killer cell number and function in Thais and North Americans.

Innate immunity may play a role in preventing HIV infection and progression to AIDS. Most studies of natural killer (NK) cell function have been conducted in populations with different HLA allele frequencies and HIV subtypes than those found in Southeast Asia. NK cell number and function, defined as CD3- cells expressing CD16+/CD56+ and the ability to lyse K562 cells, were enumerated in 42 HIV-seronegative Thais and 20 HIV-seronegative North Americans. The number and percentage of NK cells were similar for both groups, but cytotoxicity function expressed as lytic units (LU20) of NK cells was significantly greater in the Thai subjects compared with the North American subjects (p = 0.004). Comparisons were also conducted between the HIV-seronegative groups and HIV-infected subjects from both Thailand and North America. NK cell number and function were not significantly different between the Thai HIV-seronegative and -seropositive groups. However, the comparison between the North American HIV-seronegative and -seropositive subjects demonstrated profound impairment of NK cell number, percentage, and function (p < 0.001). Matching the Thai and North American HIV-infected subjects on CD4+ cell count revealed higher NK number and function in the Thai subjects (p < 0.001). The study indicates that NK function in both HIV-seronegative and -seropositive Thais is elevated relative to similar groups in North America.

Asian People↗
PubMed2000

A flow cytometric method for measuring neutralization of HIV-1 subtype B and E primary isolates.

BACKGROUND: Clinical trials testing candidate human immunodeficiency virus type 1 (HIV-1) vaccines have required the use of HIV neutralization assays to detect responses to specific geographic subtypes of HIV-1. The variability in results seen with current p24 neutralization assay endpoints prompted us to assess the utility of flow cytometry for monitoring the neutralization of HIV-1 primary isolates. METHODS: A modified neutralization assay was performed using CD8-depleted peripheral blood mononuclear cells (PBMC). The cells were fixed, permeabilized, stained with a directly conjugated HIV-1 p24 monoclonal antibody, and analyzed by flow cytometry. HIV-1 subtype B' and E primary isolates were tested using pooled sera or plasma from subtype B' or E infected patients. RESULTS: Primary isolate cultures (without neutralizing antibody) showed from 18% to 42% p24(+) cells, depending on the virus. Less than 0.2% p24(+) cells were detected in uninfected cultures. Subtype-specific neutralization of viruses was observed using plasma or serum pools; neutralization ranged from 0% to 99% reduction of infected cells. CONCLUSIONS: Flow cytometric detection of intracellular HIV-1 p24 can be used as an endpoint assay to assess neutralization of HIV-1 subtypes B' and E primary isolates. This enumerative method has the advantage of identifying intracellular p24 in specific subsets at an early culture timepoint. It also provides an alternative quantitative endpoint for HIV neutralization assays.

AIDS Vaccines↗
PubMed2000

Diversity of envelope glycoprotein from human immunodeficiency virus type 1 of recent seroconverters in Thailand.

The envelope-coding sequence of human immunodeficiency virus type 1 (HIV-1) was determined for 11 Thai seroconverters between 1995 and 1996. On the basis of the env sequences, all subjects were infected with HIV subtype E. Compared with the interpatient protein diversity among HIV-1 Thai reference sequences from 1990 to 1992 (4.4%), the diversity among the 1995-1996 seroconverters was approximately double (9.5%). The tetrapeptide tip of the V3 loop was invariant for 10 of the 11 seroconverters, and identical to that observed in sequences derived from the 1990-1992 group. However, in the V3 region, sequences from 2 of the 11 subjects demonstrated more than 5 amino acid changes relative to the reference strains. This may represent the "aging" of the HIV epidemic seen in other endemic regions. These findings may have substantial implications for vaccine development and evaluation for both HIV antibody and cytotoxic T lymphocyte repertoire recognition.

Adult↗
PubMed2000

A phase I/II trial of HIV SF2 gp120/MF59 vaccine in seronegative thais.AFRIMS-RIHES Vaccine Evaluation Group. Armed Forces Research Institute of Medical Sciences and the Research Institute for Health Sciences.

Fifty-two human immunodeficiency virus type 1, seronegative Thai adults from the community were enrolled in a double-blind, placebo controlled, phase I/II trial of HIV SF2 gp120/MF59 vaccine to determine the safety and immunogenicity of this recombinant, B clade, HIV envelope protein vaccine. Twenty-six subjects were enrolled at each of two sites in Thailand, Bangkok and Chiang Mai. Twelve subjects received placebo and 40 subjects received vaccine (50 microg). Subjects were immunized according to one of two schedules, 0, 1 and 4 or 0, 1 and 6 months. The frequency of adverse reactions was not different between placebo and vaccine subjects, nor between immunization schedules. Of vaccinees, all developed high-titer binding antibody to the immunogen (rgp120), 39 developed neutralizing antibody (NA) responses against homologous virus (HIV-1(SF2)), and 22 developed NA against heterologous virus (HIV-1(MN)). No subject demonstrated intercurrent HIV infection, however screening EIA reactivity occurred in 27% of recipients. Thus, this candidate HIV vaccine was found to be safe and immunogenic in Thai adults, laying the foundation for development of a subtype E construct in this population.

AIDS Vaccines↗
PubMed2000

The Myxococcus xanthus wbgB gene encodes a glycosyltransferase homologue required for lipopolysaccharide O-antigen biosynthesis.

Myxococcus xanthus is a gram-negative soil bacterium that initiates a complex developmental program in response to starvation. A transposon insertion (Tn5-lac omega109) mutant with developmental deficiencies was isolated and characterized in this study. A strain containing this insertion mutation in an otherwise wild-type background showed delayed developmental aggregation for about 12 h and sporulated at 1-2% of the wild-type level. Tn5-lac omega109 was found to have disrupted the M. xanthus wbgB gene, which is located 2.1 kb downstream of the M. xanthus lipopolysacharide (LPS) O-antigen biosynthesis genes wzm wzt wbgA. The deduced polypeptide sequence of WbgB shares significant similarity with bacterial glycosyltransferases including M. xanthus WbgA. The wbgB::Tn5-lac omega109 mutant was found to be defective in LPS O-antigen synthesis by immunochemical analysis. Further mutational analysis indicated that the defects of the wbgB::Tn5-lac omega109 mutant were not the result of polar effects on downstream genes. Various motility assays demonstrated that the Tn5-lac omega109 mutation affected both social (S) and adventurous (A) gliding motility of M. xanthus cells. The pleiotrophic effects of wbgB mutations indicate the importance of LPS O-antigen biosynthesis for various cellular functions in M. xanthus.

Amino Acid Sequence↗
PubMed2000

Mannosidosis: an unusual cause of a deforming arthropathy.

We report on a case of a deforming arthropathy in a young man with a lysosomal storage disorder. A 31-year-old man with a known diagnosis of mannosidosis presented with a painful swollen right elbow. Radiographs of his right elbow showed a disorganised joint with multiple fragments resembling the appearances of a neuropathic joint. This case provides further evidence that a deforming arthropathy may occur as part of the spectrum of skeletal abnormalities seen in mannosidosis.

Adult↗
PubMed2000

Selection for drug-resistant nematodes during and following extended exposure to anthelmintic.

Five groups of ten 7-month-old Romney lambs were challenged twice-weekly (2 x 3,000) with either Ostertagia circumcincta (Groups 1-3) or Trichostrongylus colubrifornzis (Groups 4 and 5) infective-stage larvae (L3) following administration of controlled release capsules (CRC) containing either albendazole (ABZ-CRC) (Groups 2 and 5) or ivermectin (IVM-CRC) (Group 3). Larval challenge comprised a mixture of equal numbers of drug-susceptible and -resistant L3 (OR/TR:OS/TS) during the 14-week period of drug release. Positive faecal egg counts (FEC) were recorded in each group during this period. Eggs recovered from faeces were used in an egg hatch assay (EHA) utilizing different concentrations of ABZ. O. circumcincta eggs from Groups 2 and 3 had significantly higher LC50 values than Group 1; eggs of T. colubriformis from the ABZ-CRC treated Group 5 had a higher LC50 than control Group 4. Following the exhaustion of drug release, larval challenge was changed to consist of only susceptible parasites and EHA performed wveekly to determine whether LC50 declined, which would indicate dilution or replacement of drench survivors. In those animals challenged with O. circumcincta, LC50 values were still significantly higher in Groups 2 and 3 at week 19 than in the previously untreated Group 1. For T. colubriformis, LC50 values declined steadily following exhaustion of drug release and were not significantly different between Groups 4 and 5 by week 20. This decline in LC50, and corresponding rise in FEC, was largely the result of 3 animals which dominated with high FEC. The remaining 6 animals showed little decline in LC50 or rise in FEC. The results demonstrate the ability of persistent drugs to screen for resistant parasites and establish that the period of selective advantage for drug-resistant parasites of both species is significantly longer than the period of drug release from CRCs.

Albendazole↗