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Biomedical subjects

J L Sullivan

Publications and source records attributed to J L Sullivan.

At least 109 records · Page 6Linked to original sources
PubMed1994

Quantitation of HIV-1 in whole blood of infected children.

OBJECTIVE: To validate the technique of HIV-1 culture from whole blood for the quantitation of viral load in infected children. PATIENTS: Forty-three HIV-1-infected children were followed in two paediatric centres. METHODS: Quantitative HIV-1 cultures from unfractionated whole blood using an end-point dilution technique were compared with simultaneous quantitative cultures of peripheral blood mononuclear cells (PBMC) and plasma. RESULTS: Good sensitivity (93%) of the methods used was confirmed. A close correlation (r = 0.80) was observed between HIV-1 titres measured directly from whole blood and those expected from PBMC and plasma titres. The mean whole blood viral load was higher in patients with more severe signs of disease, but the difference did not reach statistical significance. The whole blood viral titres measured sequentially at monthly intervals remained within one dilution of each other in 16 of the 22 patients studied. CONCLUSION: In this study, the quantitation of HIV-1 in unfractionated blood allowed for a reliable and sensitive measurement of the whole blood viral load in infected children.

Adolescent↗
PubMed1994

Effect of steam flaking of corn and sorghum grains on performance of lactating cows.

The objective of this study was to compare the relative feeding value of sorghum versus corn grain in rolled or steam-flaked forms in diets for lactating dairy cows. Twenty-four Holstein cows (averaging 110 DIM) were divided into four groups and fed diets of 40% grain as dry-rolled sorghum, steam-rolled corn, steam-flaked sorghum, or steam-flaked corn for 70 d. Compared with rolling, flaking of both grains increased yields of milk, milk protein and fat, and protein percentage of milk, but differences tended to be greater for sorghum than for corn. Efficiency of feed utilization was higher for steam-flaked than for dry-rolled sorghum but was unaffected by corn processing. Flaking of both grains increased total tract digestibilities of DM, OM, CP, starch, ADF, and NDF. Estimates for NEL were 21% higher for flaked than for rolled sorghum and 6% higher for flaked than for rolled corn. No differences in performance of cows existed between corn and sorghum grains. Cows fed 40% of their diet as steam-flaked sorghum or corn yielded more milk and milk protein than those fed the rolled form of the grains, and no differences existed between types of grain fed.

Animal Feed↗
PubMed1993

IL-2 independent growth and cytotoxicity of herpesvirus saimiri-infected human CD8 cells and involvement of two open reading frame sequences of the virus.

Herpesvirus saimiri is a primate tumor virus and induces acute T cell lymphomas and leukemias in New World monkeys and rabbits. We show in this report that infection of human peripheral white blood cells with a group C strain 484-77 results in selective expansion of CD8 lymphocytes with strong cytotoxic activity and these cells do not require interleukin-2 (IL-2) for growth. Infected cell cultures, termed herpesvirus-activated killer (HAK) cells, have been continuously maintained for several months in tissue culture and these HAK cells contain multiple copies of stable circular viral episomes. The growth and cytotoxicity of HAK cells was found independent of IL-2. Analysis of deletion mutant infected cells suggests that at least two open reading frame sequences of a bicistronic mRNA encoded by the viral genome is involved in controlling IL-2 independence. This model could facilitate studies on growth regulation of human cytotoxic T cells that are important effector cells in immune responses against infectious diseases and cancer and should help us to elucidate the mechanism of transformation by H. saimiri oncogenes.

Base Sequence↗
PubMed1993

Early viremia and immune responses in vertical human immunodeficiency virus type 1 infection.

Thirty-three infants born to human immunodeficiency virus type 1 (HIV-1)-seropositive women were evaluated from birth using plasma and peripheral blood mononuclear cell (PBMC) cultures, polymerase chain reaction, and serum p24 antigen assays. Five children were identified as infected. Evidence of infection was found in cord blood and subsequent samples from 2 infected children, suggesting in utero infection. Virologic studies on cord blood and early neonatal specimens from the 3 other infected children were negative but became positive by 8 weeks of age, suggesting either intrapartum transmission or sequestration of virus with subsequent detection. An increase in blood (plasma and PBMC) virus titers consistent with primary viremia was observed in 4 infants between 3 and 16 weeks of age. Blood virus titers subsequently declined in the absence of antiretroviral therapy and in the absence of activated HIV-1-specific cytotoxic T lymphocyte responses or broadly neutralizing antibodies. Confirmation of these results in larger studies may be helpful in the design of clinical trials to interrupt vertical transmission or to modify the course of infection.

Adult↗
PubMed1993

Human peripheral blood xenografts in the SCID mouse: characterization of immunologic reconstitution.

Immune reconstitutions (hu-PBL-SCID mice) resulting from adoptive transfer of human peripheral blood mononuclear cells into 1800 C.B-17 scid-/scid-mice were characterized. Over 90% of reconstitutions were successful as evidenced by human immunoglobulin production. Variability was noted with donor, cell number, and cell type. Human cells (T lymphocytes, few B cells) could be recovered by 5 days after engraftment. High levels of soluble CD8 and interleukin-2 receptors were detected in sera of hu-PBL-SCID mice. Cells recovered from 17 mice proliferated in response to antigens to which the donor had been primed; responses to nonboosted antigen also increased in some animals. After reconstitution, lymphocytes were found in the spleen and lymph nodes without full restoration of normal architecture. The hu-PBL-SCID mouse shows promise as a model system for a variety of immunologic studies. The inherent variation in the system must be minimized for appropriate use of the model.

Age Factors↗
PubMed1993

Nevirapine synergistically inhibits HIV-1 replication in combination with zidovudine, interferon or CD4 immunoadhesin.

OBJECTIVE: To determine whether synergistic inhibition of HIV-1 replication would result from the in vitro use of nevirapine in combination with zidovudine, interferon (IFN)-alpha 2C, and CD4 immunoadhesin. DESIGN AND METHODS: The non-nucleoside reverse transcriptase inhibitor nevirapine (formerly BI-RG-587) was tested in combination with the other antiretrovial agents. Assays were performed on stimulated peripheral blood lymphocytes infected with HIV-1. Virus replication was assessed by the release of viral p24 antigen into culture supernatants. The median-effect principle was used to assess for synergistic interactions of the combined agents. RESULTS: Zidovudine, IFN-alpha 2C and CD4 immunoadhesin, when used in combination with nevirapine, synergistically inhibited HIV-1 replication in human peripheral blood lymphocytes compared with each agent used alone. Some analyses were also consistent with additive effects, but antagonism was not noted. CONCLUSION: These in vitro findings provide a scientific basis for future trials with similar drug combinations.

Antiviral Agents↗
PubMed1993

Pharmacokinetics of nevirapine: initial single-rising-dose study in humans.

Nevirapine, a nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, was administered for the first time to humans in a pilot study designed to investigate the pharmacokinetics and tolerance of the drug following single-dose administration to 21 HIV-1-infected individuals. The study followed a parallel design. Different groups of three subjects each were given one of seven dose levels (2.5 to 400 mg) in sequential order, starting with the lowest dose. Each subject received only one dose. Nevirapine was rapidly absorbed at all doses from a tablet formulation. Peak concentrations in plasma were generally achieved within 90 min of dose administration. Secondary peaks were also noted between 3 and 12 h or between 24 and 28 h, the latter being noted mainly in subjects receiving the higher doses. After 24 h, concentrations in plasma declined in a log-linear fashion. The terminal half-life and mean residence time exceeded 24 h in all but one subject, indicating a prolonged disposition time in this population. Both peak concentrations in plasma and areas under the plasma concentration-time curves increased proportionally with increasing dose from 2.5 to 200 mg; however, the increase in the peak concentration in plasma and the area under the plasma concentration-time curve appeared to be less than proportional at the 400-mg dose level in this small number of subjects. This observation may be due to increased clearance or decreased absorption at the highest dose or population differences in absorption or clearance between doses. Studies with a cross-over design are planned to resolve these issues. The pharmacokinetic characteristics of nevirapine are appropriate for once-daily administration. A daily 12.5-mg dose is predicted to achieve trough concentrations in plasma in the range required to totally inhibit replication of wild-type HIV-1 in human T-cell culture.

Acquired Immunodeficiency Syndrome↗