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Biomedical subjects

H Sheppard

Publications and source records attributed to H Sheppard.

At least 19 recordsLinked to original sources
PubMed2001

Safety and immunogenicity of a canarypox-vectored human immunodeficiency virus Type 1 vaccine with or without gp120: a phase 2 study in higher- and lower-risk volunteers.

Live attenuated viral vectors that express human immunodeficiency virus (HIV) antigens are being developed as potential vaccines to prevent HIV infection. The first phase 2 trial with a canarypox vector (vCP205, which expresses gp120, p55, and protease) was conducted in 435 volunteers with and without gp120 boosting, to expand the safety database and to compare the immunogenicity of the vector in volunteers who were at higher risk with that in volunteers at lower risk for HIV infection. Neutralizing antibodies to the MN strain were stimulated in 94% of volunteers given vCP205 plus gp120 and in 56% of volunteers given vCP205 alone. CD8(+) cytotoxic T lymphocyte cells developed at some time point in 33% of volunteers given vCP205, with or without gp120. Phase 3 field trials with these or similar vaccines are needed, to determine whether efficacy in preventing HIV infection or in slowing disease progression among vaccinees who become infected is associated with the level and types of immune responses that were induced by the vaccines in this study.

AIDS Vaccines↗
PubMed2001

Comparison of techniques for HIV-1 RNA detection and quantitation in cervicovaginal secretions.

PRINCIPLES: HIV-1 in female genital secretions has been measured using swabs, Sno Strips (Akorn, Inc., Buffalo Grove, IL), and cervicovaginal lavage (CVL), but little is known regarding the comparability of these collection techniques. METHODS: We compared HIV-1 RNA detection and quantity in specimens obtained from HIV-1-seropositive women in Kenya using three sample collection techniques and three storage techniques and evaluated reproducibility in samples collected 5 days apart. Specimens were stored in no medium, freezing medium, or TRI Reagent (Molecular Research Center, Cincinnati, OH) for 2 to 15 months. RESULTS: HIV-1 RNA assays were conducted on 640 specimens from 20 antiretroviral naive women. Storage in TRI Reagent significantly enhanced detection of genital HIV-1 and yielded significantly higher mean log10 RNA levels than specimens collected in either no or freezing medium. The prevalence of HIV-1 RNA detection in TRI Reagent ranged from 50% to 80% depending on collection method and was highest in cervical swabs. Mean log10 HIV-1 RNA levels were 3.1 log10 copies/cervical swab, 2.6 log10 copies/cervical Sno Strip, 2.5 log10 copies/vaginal swab, 2.4 log10 copies/vaginal Sno Strip, 2.9 log10 copies/ml for cervicovaginal lavage (CVL) cell pellet, and 2.1 log10 copies/ml in CVL supernatant. Comparing specimens from days 1 and 6, there was significant concordance of HIV-1 RNA detection and correlation of HIV-1 RNA levels for cervical swabs, vaginal swabs, vaginal Sno Strips, and CVL cell pellets (kappa, 0.5-0.9; r, 0.5-0.9), but not for cervical Sno Strips or CVL supernatants. CONCLUSIONS: Cervical or vaginal swab, vaginal Sno Strip, and CVL collection led to reproducible measurement of genital HIV-1 RNA, despite storage for several months and international transport. Collection using swabs was simpler than Sno Strips or cervicovaginal lavage, and yielded the highest prevalence of HIV-1 RNA detection and reproducibility.

Cervix Uteri↗
PubMed2000

Core LXXLL motif sequences in CREB-binding protein, SRC1, and RIP140 define affinity and selectivity for steroid and retinoid receptors.

An alpha-helical motif containing the sequence LXXLL is required for the ligand-dependent binding of transcriptional co-activators to nuclear receptors. By using a peptide inhibition assay, we have defined the minimal "core" LXXLL motif as an 8-amino acid sequence spanning positions -2 to +6 relative to the primary conserved leucine residue. In yeast two-hybrid assays, core LXXLL motif sequences derived from steroid receptor co-activator (SRC1), the 140-kDa receptor interacting protein (RIP140), and CREB-binding protein (CBP) displayed differences in selectivity and affinity for nuclear receptor ligand binding domains. Although core LXXLL motifs from SRC1 and RIP140 mediated strong interactions with steroid and retinoid receptors, three LXXLL motifs present in the global co-activator CBP were found to have very weak affinity for these proteins. Core motifs with high affinity for steroid and retinoid receptors were generally found to contain a hydrophobic residue at position -1 relative to the first conserved leucine and a nonhydrophobic residue at position +2. Our results indicate that variant residues in LXXLL core motifs influence the affinity and selectivity of co-activators for nuclear receptors.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Home collection for frequent HIV testing: acceptability of oral fluids, dried blood spots and telephone results. HIV Early Detection Study Group.

OBJECTIVE: To assess the feasibility and acceptability of bimonthly home oral fluid (OF) and dried blood spot (DBS) collection for HIV testing among high-risk individuals. DESIGN: A total of 241 participants [including men who have sex with men (MSM), injecting drug users (IDU), and women at heterosexual risk] were recruited from a randomly selected subset of study participants enrolled at four sites in the HIV Network for Prevention Trials (HIVNET) cohort, and assigned at random to bimonthly home collection of OF or DBS specimens over a 6 month interval. Participants could select telephone calls or clinic visits to receive HIV test results. METHODS: Bimonthly specimens were tracked for adherence to the schedule, were evaluated for adequacy for testing, and tested using antibody assays and polymerase chain reaction (PCR) for DBS. The acceptability of bimonthly home OF and DBS collection and telephone counseling was assessed in an end-of-study questionnaire. RESULTS: The laboratory received 96 and 90% of expected OF and DBS specimens, respectively; 99% of each specimen type was adequate for testing. Almost all (95%) participants chose results disclosure by telephone. The majority of participants (85%) reported that bimonthly testing did not make them worry more about HIV, and almost all (98%) judged that with bimonthly testing their risk behavior remained the same (77%) or became less risky (21%). CONCLUSION: Bimonthly home specimen collection of both OF and DBS with telephone counseling is acceptable and feasible among study participants at high risk. These methods will be useful for the early detection of HIV infection and remote follow-up of research cohort participants in HIV vaccine and prevention trials.

AIDS Serodiagnosis↗
PubMed2000

PCR-Based assay to quantify human immunodeficiency virus type 1 DNA in peripheral blood mononuclear cells.

An assay that quantifies the amount of human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells has been developed. PCR amplification of the HIV-1 DNA is performed in the presence of an internal quantitation standard, and colorimetric detection of the amplified product is performed with microwell plates. The copies of HIV-1 DNA are normalized to total genomic DNA input. The assay has an analytical sensitivity of 10 input copies per amplification reaction and a three-log detection range. In an analysis of sequential samples from patients on combination therapy, HIV-1 DNA was quantifiable for all individuals tested, including those with undetectable plasma HIV-1 RNA. In a separate study, a comparison of HIV-1 DNA levels was made with a group of long-term survivors and progressors. The mean HIV-1 DNA levels were lower in the long-term survivors than in the progressors (P, 0.04). The mean HIV-1 RNA levels were also lower, but the difference was not statistically significant (P, 0.164). A quantitative DNA assay will provide an additional tool to gain insight into the natural history of infection and the continued efficacy of potent antiretroviral therapies.

Anti-HIV Agents↗
PubMed1999

Human immunodeficiency virus type 1-specific cytotoxic T lymphocyte activity is inversely correlated with HIV type 1 viral load in HIV type 1-infected long-term survivors.

HIV-1-specific cytotoxic T cell (CTL) activity has been suggested to correlate with protection from progression to AIDS. We have examined the relationship between HIV-specific CTL activity and maintenance of peripheral blood CD4+ T lymphocyte counts and control of viral load in 17 long-term survivors (LTSs) of HIV-1 infection. Longitudinal analysis indicated that the LTS cohort demonstrated a decreased rate of CD4+ T cell loss (18 cells/mm3/year) compared with typical normal progressors (approximately 60 cells/mm3/year). The majority of the LTSs had detectable, variable, and in some individuals, quite high (>10(4) RNA copies/ml) plasma viral load during the study period. In a cross-sectional analysis, HIV-specific CTL activity to HIV Gag, Pol, and Env proteins was detectable in all 17 LTSs. Simultaneous analysis of HIV-1 Gag-Pol, and Env-specific CTLs and virus load in protease inhibitor-naive individuals showed a significant inverse correlation between Pol-specific CTL activity and plasma HIV-1 RNA levels (p = 0.001). Furthermore, using a mixed linear effects model the combined effects of HIV-1 Pol- and Env-specific CTL activity on the viral load were significantly stronger than the effects of HIV-1 Pol-specific CTL activity alone on predicted virus load. These data suggest that the presence of HIV-1-specific CTL activity in HIV-1-infected long-term survivors is an important component in the effective control of HIV-1 replication.

CD4 Lymphocyte Count↗
PubMed1997

Cross-clade human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte responses in HIV-infected Zambians.

We have examined cross-clade HIV-specific cytotoxic T-lymphocyte (CTL) activity in peripheral blood of eight Zambian individuals infected with non-B-clade human immunodeficiency virus type 1 (HIV-1). Heteroduplex mobility assay and partial sequence analysis of env and gag genes strongly suggests that all the HIV-infected subjects were infected with clade C HIV-1. Six of eight C-clade HIV-infected individuals elicited CTL activity specific for recombinant vaccinia virus-infected autologous targets expressing HIV gag-pol-env derived from B-clade HIV-1 (IIIB). Recognition of individual recombinant HIV-1 B-clade vaccinia virus-infected targets expressing gag, pol, or env was variable among the patients tested, indicating that cross-clade CTL activity is not limited to a single HIV protein. These data demonstrate that HIV clade C-infected individuals can mount vigorous HIV clade B-reactive CTL responses.

Cross Reactions↗
PubMed1990

Noise-induced threshold elevation as a function of peak sound pressure level.

Thirty-three groups of guinea pigs, consisting of five animals in each group, were exposed to a simulated impact noise with peak levels ranging between 119.5 and 134.5 dB SPL. By varying the repetition rate, different equivalent levels could be set at each peak level. The equivalent levels ranged from 96 to 117 dB SPL, and the exposure duration was 1.5 to 24 hours. The compound action potential thresholds were measured in 1/3-octave steps between 1 and 20 kHz, one month after the exposure. Higher peak levels resulted in a peak-shaped threshold elevation with a maximum around 8 kHz. For constant peak levels, the equal energy theory was supported. For exposures of equal energy but different peak levels, significantly higher threshold elevations resulted after exposure to higher peak levels.

Animals↗
PubMed1988

Action potential threshold elevation in the guinea-pig as a function of impact noise exposure energy.

Eighteen groups of guinea pigs were exposed to a simulated impact noise for periods of 1.5-24 h. The peak level was kept constant at 131.5 dB and the repetition rate was varied to give seven different equivalent levels (Leq) between 96 and 117 dB. The auditory thresholds were assessed by electrocochleography after 1 month and compared with those of a control group. Significant damage occurred even at the lowest exposure energy used. When the total exposure energy was expressed on a decibel scale, the threshold elevation (1-10 kHz) increased 1.07 dB for each decibel increase in the exposure energy, regardless of the combination of Leq and exposure time. The results of the study thus support the equal-energy hypothesis under these conditions.

Animals↗
PubMed1985

The effect of tri-iodothyronine (T3) on protein turnover and metabolic rate.

Obese patients who had an unusually slow weight loss on a restricted energy intake (2 MJ/d) were treated for approximately two weeks with small doses of T3 (20 micrograms three times daily). At the beginning and end of treatment whole body protein turnover was measured with a single dose of 15N-glycine and both ammonia and urea as end-products. T3 increased the rate of weight loss, with a significant increase in urinary nitrogen excretion. There were small increases in basal metabolic rate and protein turnover, which were not significant. It is concluded that the extra weight loss produced by T3 was at the expense of lean body mass and not of fat.

Adult↗
PubMed1983

Gallium 67 scanning in rheumatoid arthritis.

Gallium 67 scans were performed on both knees of 38 patients with rheumatoid arthritis. There was a significantly higher level of 67Ga accumulation in those knees with clinically active synovitis (p less than 0.001). Synovial white cell concentration was also elevated in the group with active synovitis. The white cell concentration correlated with the 67Ga knee/femoral ratio at the p less than 0.001 level. 67Ga activity in the synovial fluid was predominantly in the supinate and activity was also present in the synovium. The findings indicate that 67Ga uptake occurs in rheumatoid joints and reflects the degree of synovial inflammation.

Arthritis, Rheumatoid↗
PubMed1983

Hearing deterioration in shipyard workers. Serial audiometry over a four-year period.

The hearing thresholds of a total of 58 workers aged 20 to 65 years were measured annually over a period of 4 years using Békésy sweep-frequency audiometry. Using these data, accurate values of the yearly rate of change of hearing threshold level were calculated. The rate of change of hearing threshold level due to presbyacusis was obtained from several data sets, and the rate of change of hearing threshold level due to noise was calculated. When the average hearing threshold level over the frequency range 2-8 kHz was considered, it was found to be possible to establish a significant rate of threshold shift caused by exposure to noise for yearly changes as small as approximately 2 dB. In the cases investigated about 30% of the ears showed a significant deterioration in hearing ability due to noise. When comparing the permanent threshold shift caused by noise in groups of younger and older workers, it was found that the younger workers exhibited less threshold shift than expected, whereas the older workers showed a greater threshold shift than expected.

Adult↗
PubMed1982

The lack of correlation between inhibition of aggregation and cAMP levels with canine platelets.

Arachidonic acid (AA) induced aggregation of canine platelets can be inhibited by various phosphodiesterase inhibitors (PDIs) with the order of potency IBMX greater than or equal to papaverine greater than Ro 20-1724 greater than theophylline. With aggregation induced by AA plus epinephrine (EPI), only IBMX and papaverine inhibited at 100 microM. None of these PDIs affected the basal cAMP levels but all potentiated the PGE1-stimulated cAMP production, with the order of potency being Ro 20-1724 greater than papaverine greater than IBMX greater than theophylline. PGE1 at 1 microM caused a sharp increase in cAMP and complete inhibition of platelet aggregation induced by AA plus EPI. However, when EPI was added before PGE1, there was no elevation of cAMP yet inhibition of aggregation still occurred. Our results indicated that inhibition of platelet aggregation does not require a measurable increase in cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1981

The elevation of mouse thymus cell cyclic adenosine monophosphate (cAMP) by lipopolysaccharide.

The ability of certain lipopolysaccharide (LPS) preparations to elevate cyclic adenosine monophosphate (cAMP) in mouse thymus cells in the presence of Ro 20-1724, 4-(3-butoxyl 4-methoxybenzyl)-2-imidazolidinone, was not related to the source of supply, bacterial strain, or method of extraction. Under the same conditions adenosine is a potent stimulator of thymus cell cAMP and is, of course, blocked by the further addition of theophylline. When theophylline was added to the LPS preparations with Ro 20-1724, the cAMP production was also blocked. These studies suggested that the observed stimulation of cAMP by LPS preparations was due to adenosine and/or its nucleotides present as contaminants.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗