Biomedical subjects

R B Pollard

Publications and source records attributed to R B Pollard.

At least 37 records · Page 2Linked to original sources

PubMed1999

Analogy of human immunodeficiency virus to hepatitis C virus: the human immunodeficiency model.

The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) for many years overshadowed hepatitis C, which we now know is in some ways an even bigger problem. Important differences also exist between these two viruses and the diseases they cause, and we must be cautious about drawing too close an analogy. However, there are some striking similarities, and many lessons have been learned from HIV research over the past two decades. Parallels with HIV include persistence of the virus, genetic diversity during replication in the host, and the utility of combination treatment that is just now being appreciated with HCV infection. In the last few years, targeted antiviral drugs, such as protease inhibitors, have had an impressive effect on HIV-related morbidity and mortality. Similarities in the HIV and HCV genomes suggest that such drugs may also be useful in treating hepatitis.

AIDS-Related Opportunistic Infections↗

PubMed1999

Cytokine production by rabbit alveolar macrophages: differences between activated and suppressor cell phenotypes.

The differences between cytokine-producing profiles of activated macrophages (A-M phi) and suppressor macrophages (S-M phi) were examined. A-M phi, which exhibited cytotoxicity against RK-13 cells, were generated from resident rabbit alveolar M phi by treatment with lymphokine solution (culture fluids of rabbit spleen cells stimulated with concanavalin A [Con A]). S-M phi, which were able to inhibit cellular proliferations of rabbit spleen cells stimulated with Con A, were generated from resident alveolar M phi by treatment with 1-methyladenosine (an immunosuppressive molecule in tumourous ascites fluids). When A-M phi were stimulated with lipopolysaccharide (LPS) in vitro, the cells produced significantly more interleukin (IL)-1 (approximately 1.4 times), IL-6 (approximately 2.1 times), IL-12 (approximately 60 times), and tumour necrosis factor-alpha (TNF-alpha) (approximately 37 times) than did resting macrophages (R-M phi) stimulated with LPS as control cells. After the stimulation with LPS, both A-M phi and R-M phi did not produce transforming growth factor-beta (TGF-beta). In contrast, when S-M phi were stimulated with LPS in vitro, the cells produced significantly more TGF-beta (approximately 1.6 times) and significantly less IL-6 (approximately 1.8 times) than did control cells. Also, S-M phi did not produce IL-1, IL-12, and TNF-alpha into their culture fluids after the stimulation with LPS. These results show the differences between cytokine-producing profiles of A-M phi and S-M phi, and characteristics of their cytokine-producing profiles are analogous to T cell subsets. Differences displayed in the cytokine profiles may contribute to the effector (A-M phi) or the suppressor (S-M phi) functions of alveolar M phi.

Animals↗

PubMed1999

Safety and antiretroviral effects of combined didanosine and stavudine therapy in HIV-infected individuals with CD4 counts of 200 to 500 cells/mm3.

The safety and antiretroviral effects of didanosine and stavudine in combination were evaluated in 86 people infected with HIV with CD4 counts between 200 and 500 cells/mm3 who had received <7 days of prior nucleoside analogue antiretroviral treatment. Patients were randomized to receive blinded treatments with one of five weight-adjusted, twice-daily regimens of didanosine and stavudine (100 + 10 mg, 100 + 20 mg, 100 + 40 mg, 200 + 20 mg, and 200 + 40 mg) for up to 1 year. Dosages were adjusted appropriately for patients weighing <60 kg and reduced in response to adverse effects. No clear dose-related differences among treatment groups were detected with regard to suppression of plasma HIV RNA level or reduction in infectious titers in peripheral blood mononuclear cells (PBMCs), improvement in CD4 count, or adverse effects. However, trends toward greater decreases in viral load and increases in CD4 count were detected when treatment groups containing the full recommended dosage of one or both agents (high-dose subgroup; arms 3, 4, and 5) were compared with the groups receiving lower dosages. At 28 weeks the mean log 10 HIV RNA decrease was 1.12 (n = 52) and at 52 weeks it was 0.97 (n = 32). Combination therapy was well tolerated, with no apparent dose-related adverse effects. Peripheral neuropathy occurred in 2 of 86 (2.3%) of patients. Didanosine and stavudine together appear to be a good nucleoside analogue foundation for aggressive triple- or quadruple-drug therapy. Full therapeutic doses of each of these two agents should be used to achieve optimal suppression of HIV replication.

Adult↗

PubMed1999

Virological and immunological responses to once-daily dosing of didanosine in combination with stavudine. AI454-143 Team.

OBJECTIVE: To compare the antiviral activity of once-daily didanosine (ddI) and twice-daily ddI in combination with stavudine (d4T). DESIGN: Randomized, double-blind, multicenter study. SETTING: Twenty-one sites in the United States. PATIENTS: Eighty-seven antiretroviral-naive, HIV-1-infected adults with baseline plasma HIV RNA counts of > or = 10,000 copies/ml and CD4 cell counts of > or = 100 cells/mm3 started study therapy. INTERVENTIONS: Patients received once-daily ddI or twice-daily ddI, each combined with twice-daily d4T. MAIN OUTCOME MEASURES: Plasma HIV-1 RNA levels, CD4 cell counts, and adverse events were regularly monitored. The primary efficacy analysis used was the time-averaged difference (TAD) between treatment regimens in change from baseline plasma HIV-1 RNA levels over the first 12 weeks of therapy. RESULTS: At week 12, median log10 HIV-1 RNA changes were -1.83 log10 copies/ml in the once-daily ddI/d4T group and -1.80 log10 copies/ml in the twice-daily ddI/d4T group, and 18 out of 44 patients (41%) and 17 out of 43 patients (40%), respectively, had HIV-1 RNA levels below 400 copies/ml. Similar results were seen at week 24. The TAD between the two treatment groups (once-daily ddI/d4T minus twice-daily ddI/d4T) in change from baseline plasma HIV RNA levels over the first 12 weeks was 0.14 log10 copies/ml (95% CI: -0.11, 0.40). At week 12, subjects averaged an increase in CD4 cell count of over 140 cells/mm3. The TAD between the two treatment groups in change from baseline CD4 cell counts over the first 12 weeks was 2 cells/mm3 (95% CI: -40, 45). CONCLUSION: Once-daily ddI plus d4T and twice-daily ddI plus d4T were similarly effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts over 12-24 weeks of therapy.

Adult↗

PubMed1999

Therapeutic protective effects of IL-12 combined with soluble IL-4 receptor against established infections of herpes simplex virus type 1 in thermally injured mice.

The effect of combination therapy between IL-12 and soluble IL-4R (sIL-4R) on the established infection of HSV-1 in thermally injured mice (TI mice) was investigated. All of the TI mice infected with lethal amounts of HSV-1 died when IL-12 was given therapeutically at a dose of 500 U/mouse. However, 80% of these mice treated prophylactically with IL-12 survived compared with 0% survival of the same mice treated with saline. The therapeutic administration of IL-12 to TI mice currently infected with HSV-1 caused an 80% survival of these mice when the treatment was combined with sIL-4R. Although IL-12 did not stimulate IFN-gamma production in cultures of splenic T cells from TI mice, IFN-gamma was produced by stimulation with IL-12 when the producer cells were prepared from TI mice that had been treated previously with sIL-4R. After stimulation with anti-CD3 mAb, splenic T cells from TI mice with the established infection of HSV-1 produced IL-4 into their culture fluids. However, IL-4 was not produced by splenic T cells that were prepared from the same infected mice treated with IL-12 and sIL-4R in combination. The results obtained herein indicate that the efficacies of the combination therapy against the established infection of HSV-1 may result from the IFN-gamma production stimulated by IL-12 in TI mice that are treated with sIL-4R for reducing burn-associated type 2 T cell responses.

Animals↗

PubMed1999

Effect of didanosine, stavudine, and hydroxyurea therapy on apoptosis in CD45RA+ and CD45RO+ T lymphocyte subpopulations.

The effect of aggressive antiretroviral therapy on spontaneous apoptosis (AP) in CD4+ and CD8+ lymphocytes expressing CD45RO (memory cells) and CD45RA (naive cells) and their relationship to cellular activation and viral load were examined. Ten patients receiving simultaneous treatment with d4T, ddI, and HU were evaluated. Flow cytometric analysis showed significant levels of AP (measured by TUNEL assay) among memory and naive T cells and an enhanced expression of CD38 and HLA-DR activation markers. The percentage of apoptotic CD4+CD45RO+ and CD4+CD45RA+ cells decreased, respectively, from 34 +/- 3.3 and 29 +/- 3.6 prior to treatment to 20.5 +/- 4 and 22 +/- 3.8 at week 8 into therapy. The percentage of apoptotic CD8+CD45RO+ and CD8+CD45RA+ cells similarly decreased, respectively, from 20 +/- 2.5 and 24 +/- 3 prior to treatment to 14.5 +/- 2.7 and 16 +/- 3 at week 8 into treatment. The percentage of CD4+ cells expressing the activation markers CD38 and HLA-DR decreased from 27 +/- 6 to 13 +/- 2 and from 26 +/- 4 to 13.5 +/- 3, respectively. The percentage of CD8+ cells expressing either CD38 or HLA-DR fell from 22 +/- 3 to 10 +/- 2 for the former and from 39 +/- 5 to 22 +/- 4 for the latter. This was associated with a significant decrease in viral load (mean, 1.4 log10), and a decline in circulating plasma TNF-alpha and sIL-2R levels from 50.5 +/- 10 to 21 +/- 6 and 92.5 +/- 11 to 68 +/- 9, respectively. These data indicate that short-term therapy with ddI, d4T, and HU in combination diminished AP, immune activation, and partially restored naive and memory T cell subpopulations.

Adult↗

PubMed1999

Cadaveric skin allograft-associated cytomegalovirus transmission in a mouse model of thermal injury.

As a routine procedure to provide temporary coverage for burn wounds, cadaveric skin allografts have been used in patients with massive thermal injuries. In this study, CMV infection associated with skin grafting was investigated. Graft-associated CMV transmission was shown in a mouse model of thermal injury. Skins from mice 100 days after a nonlethal dose of murine CMV (MCMV) infection contained MCMV DNA and mRNA, although the virus was not isolated from these murine skins. When these skins were grafted to burned mice, the marked growth of MCMV was demonstrated in salivary glands. No viral growth was shown in the salivary glands of unburned mice or CMV sero(+) mice after grafting with these skins. When severe combined immunodeficient beige (SCID-beige) mice were used as recipients for CMV sero(+) skins, all mice died within 30 days after the grafting. Only 1 PFU/mouse of MCMV was shown to be 1 LD(50) in SCID-beige mice, while a 50% mortality rate was shown in normal unburned mice infected with 5 x 10(5) PFU/mouse of MCMV. This indicates that a very small amount of CMV contained in skins is sufficient to induce CMV infection in immunocompromised hosts. On the other hand, human CMV (HCMV) DNA and mRNA were detected by PCR analysis in 55% (DNA) and 33% (mRNA) of cadaveric skins, although the isolation of HCMV from cadaveric skin homogenates was not achieved in tissue cultures. CMV sero(-) patients with severe burn injuries may have a high risk for CMV infection associated with allografts of cadaveric skins.

Animals↗

PubMed1999

Effects of glycyrrhizin, an active component of licorice roots, on Candida albicans infection in thermally injured mice.

Due to the generation of burn-associated CD8+ CD11b+ TCR gamma/delta+ type 2 T cells (burn-associated type 2 T cells), the susceptibility of thermally injured mice to infection with C. albicans has been shown to be increased by up to 50-fold when compared with normal mice. Glycyrrhizin (GR), an active component of licorice roots, reduced the susceptibility of thermally injured mice to C. albicans infection to levels observed in normal mice. Thermally injured mice inoculated with CD4+ T cells from GR-treated mice were also resistant to C. albicans infection. The following demonstrated that susceptibility to fungal infection was similar in thermally injured mice and normal mice inoculated with T6S cells (a clone of burn-associated type 2 T cells). This susceptibility of T6S mice (normal mice inoculated with T6S cells) was reversible by (i) administration of GR, (ii) inoculation of CD4+ T cells from GR-treated mice, and (iii) injection of a mixture of MoAbs targeted against type 2 cytokines (IL-4 and IL-10). After stimulation with anti-CD3 MoAb, splenic T cells from thermally injured and T6S mice, treated with GR or inoculated with CD4+ T cells from GR-treated mice, did not have type 2 cytokines in culture supernatants. They were present in splenic T cell cultures from thermally injured and T6S mice that were treated with saline or inoculated with naive T cells. These results suggest that GR, by inducing CD4+ T cells which suppress type 2 cytokines produced by burn-associated type 2 T cells, improves the resistance of thermally injured mice to C. albicans. An anti-type 2 T cell action of the CD4+ T cells derived from GR-treated mice was previously described.

Amphotericin B↗

PubMed1999

Antiviral effect of gingyo-san, a traditional Chinese herbal medicine, on influenza A2 virus infection in mice.

Gingyo-san is a crude drug containing extracts from 7 medicinal plants and fermented soybeans in a specific ratio. It has been used clinically in China as a therapeutic agent for the common cold. In the present study, we examined the antiviral effect of this agent on influenza virus infection in mice. Gingyo-san and its components were administered orally to mice 1 day before, then 1 and 4 days after the inhalation of a mouse-adopted strain of influenza A2 (H2N2) virus. After infection with a 10 LD50 of the virus, 100% of mice treated with 10 mg/kg of the agent survived as compared with a 0% survival of control mice treated with saline. Also, the mean survival days were increased and consolidation scores were decreased in treated mice as compared with those of control mice. Two components contained in the agent, extracts from Glycyrrhizae radix and Arctii fructus, expressed antiviral activities in mice infected with influenza virus. However, in vitro growth of influenza virus in MDCK cells or viability of the virus was not affected by these extracts or Gingyo-san. From these results Gingyo-san was shown to be an antiviral agent in mice infected with a lethal amount of a mouse-adopted strain of influenza A2 virus.

Animals↗

PubMed1999

[Biological properties of T6S cells, a clone of burn-associated type 2 T cells].

A clone of type 2 T cells (T 6 S cell) was established from burn-associated CD 8+ CD 11 b+ TCR gamma/delta + type 2 T cells, and their biological properties were examined. After stimulation by anti-CD 3 monoclonal antibody (mAb), T 6 S cells produced IL-4 and IL-10 into their culture fluids. However, IFN-gamma and IL-2 were not demonstrated in the culture fluids of T 6 S cells stimulated with the mAb. The susceptibility of thermally injured mice to infection with herpes simplex virus type 1 (HSV-1) or Candida albicans (C. albicans) has been shown to be approximately 50 (C. albicans) to 100 (HSV-1) times greater than that of normal mice. As compared with the resistance of thermally injured mice to these pathogens, mice inoculated with 1 x 10(6) cells/mouse of T 6 S cells (designated as T 6 S-mice) showed the same susceptibility to the infections. When T 6 S-mice treated with a mixture of monoclonal antibodies (mAbs) directed against IL-4 and IL-10 were infected with a lethal dose of HSV-1 or C. albicans, their resistance to these pathogens was restored to levels found in normal mice. From the experiments using T 6 S-mice, it is suggest that type 2 T cells or their cytokine products (IL-4 and IL-10) may play an important role on the impaired resistance of thermally injured mice to certain opportunistic pathogens. T 6 S cell may be a useful tool to study opportunistic infections in hosts bearing type 2 T cells.

Animals↗

PubMed1998

A pathogenic role of Th2 cells and their cytokine products on the pulmonary metastasis of murine B16 melanoma.

The role of Th2 cells and the cytokines produced by these cells on experimental pulmonary metastasis of B16 melanoma was investigated in a murine model implanted with high metastatic (B16F10) or low metastatic (B16F1) melanoma cells. An average of 250 colonies of metastasis in the lungs was counted in mice (BF10 mice) at 14 days after the inoculation of 2 x 10(5) B16F10 cells/mouse, while <20 colonies were detected in mice (BF1 mice) inoculated with the same number of B16F1 cells. CD4+ CD11b+ TCR-alphabeta+ T cells (BF10-Th2 cells) were produced in the spleens of BF10 mice, while these cells were not detected in BF1 mice. The BF10-Th2 cells produced IL-4 and IL-10 into culture fluids when stimulated in vitro with anti-CD3 mAb. However, IL-2 and IFN-gamma were not produced. The level of a pulmonary metastasis in BF1 mice increased to the level observed in BF10 mice, when BF10-Th2 cells were adoptively transferred to BF1 mice. Also, an increase in the number of pulmonary melanoma was demonstrated in BF1 mice treated with 10 microg/kg murine rIL-4. The level of pulmonary metastasis in BF10 mice or in BF1 mice inoculated with BF10-Th2 cells decreased to the level observed in BF1 mice when mice were treated with an anti-IL-4 mAb at a dose of 250 microg/kg on days 1, 3, and 5 after tumor inoculation. These results suggest that the severity of pulmonary metastasis in mice receiving B16 melanoma cells is strongly influenced by the IL-4 released from tumor-associated Th2 cells.

Adoptive Transfer↗

PubMed1998

Burn-associated Candida albicans infection caused by CD30+ type 2 T cells.

Burn injury is associated with the greatly increased susceptibility of thermally injured patients to infection from a variety of pathogens. In this study we investigated the role of burn-associated type 2 T cells on the increased susceptibility of burned patients to Candida albicans infection using SCID mice and peripheral blood lymphocytes (PBL) from thermally injured patients. When SCID mice that were inoculated with PBL from healthy donors were resistant to C. albicans infection, the SCID mice that were inoculated with PBL from burned patients did not show any resistance to the infection. All SCID mice exposed to the pathogen, however, survived after inoculation with patient PBL that were previously depleted of CD30+ cells. The predominance of type 2 T cell responses was demonstrated in PBLs of thermally injured patients. As burn-associated type 2 T cells, CD3+ CD8+ CD30+ IL-4 and IL-10-producing cells were demonstrated in burned patient PBL. These results suggest that burn-associated CD30+ type 2 T cells may play a role on the increased susceptibility of burned patients to C. albicans infection.

Adolescent↗

PubMed1998

The regulation of burn-associated infections with herpes simplex virus type 1 or Candida albicans by a non-toxic aconitine-hydrolysate, benzoylmesaconine. Part 1: Antiviral and anti-fungal activities in thermally injured mice.

As compared with normal unburned mice, thermally injured mice have been shown to be 50-100 times more susceptible to HSV type 1 (HSV-1) or Candida albicans infection. Benzoylmesaconine (BEN) improved the resistance of thermally injured mice against infection with HSV-1 or C. albicans to the level observed in normal mice. Mortality rates of normal mice exposed to lethal amounts of these pathogens were not affected by the BEN treatment, while significant survival effects were produced in these mice after treatment with acyclovir (against HSV-1) or amphotericin B (against C. albicans). Benzoylmesaconine did not inhibit the growth of these pathogens in vitro and did not directly reduce the viability of the pathogens. However, burned mice inoculated with CD4+ T cells from BEN-treated mice resisted infections from these pathogens. These results suggested that, through the generation of CD4+ T cells, BEN recovered the impaired resistance of thermally injured mice to infection by HSV-1 or C. albicans.

Aconitine↗

PubMed1998

A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group.

Cytomegalovirus (CMV) disease is a common complication of advanced human immunodeficiency virus (HIV) infection. Administration of oral valaciclovir, a valine ester of acyclovir, achieves sufficient plasma acyclovir levels to inhibit many clinical isolates. Acyclovir has been associated with enhanced survival in AIDS but not with CMV disease prevention. CMV-seropositive patients (1227) with CD4 cell counts <100/mm3 were enrolled in a randomized, double-blind trial. Valaciclovir, 8 g/day, was compared with acyclovir, 3.2 or 0.8 g/day, for CMV prevention; all three arms were compared for survival. The confirmed CMV disease rate was 11.7% among valaciclovir recipients and 17.5% in the pooled acyclovir arms, a 33% reduction in risk. Time to confirmed CMV disease was significantly longer for the valaciclovir group (P = .03). A trend toward earlier mortality for valaciclovir recipients was seen (P = .06). Toxicity and earlier medication discontinuation were more common in this group. Valaciclovir significantly reduces the risk of CMV disease. Further exploration of a better-tolerated dose is warranted.

AIDS-Related Opportunistic Infections↗

PubMed1998

HIV decreases glutamate transport in SK-N-MC neuroblastoma cells.

Autopsy studies of patients with AIDS dementia have shown neuronal loss consistent with a neurotoxic component of this disease. In vitro studies suggest that viral products or cytokines from HIV-infected macrophages (Mphi) may modulate or directly mediate excitotoxic cell death of neurons. Mphi differentiated from peripheral mononuclear blood cultures were infected with HIV, and conditioned media (CM) were harvested from these cultures. Exposure of SK-N-MC (neuroblastoma) cells to CM from HIV-infected Mphi for 4, 24 or > or = 48 h resulted in a mean suppression of 12-34% of the glutamate transport Vmax with no appreciable change in transport Km. An astrocytoma tumor cell, U373MG, showed similar CM-mediated glutamate uptake suppression. Changes were evident in total and Na+-dependent glutamate uptake, with significantly more suppression of Na+-dependent uptake. Similar effects were seen with the nonmetabolizable transporter agonist D-aspartate, indicating that the effect was on transport and not metabolism. No suppression was seen with CM from uninfected Mphi or Mphi infected with heat-inactivated HIV. The magnitude of uptake suppression was not correlated with CM p24 values, and removal of CM virions by ultracentrifugation and immunoprecipitation did not alter the uptake-suppressive properties of infected Mphi CM. Uptake suppression was seen when Mphi were infected with Mphi-tropic strains HIV(SF162), HIV(JR-CSF), HIV(NFN-SX) and a Mphi-tropic patient isolate, but not the lymphotropic strain HIV(LAI). HIV-infected Mphi may produce substances which suppress neuronal and glial glutamate neurotransmitter uptake, resulting in higher extracellular glutamate levels and leading possibly to deficits in cell signaling and neurotoxicity.

Biological Transport↗

PubMed1997

Kinetics of tumor necrosis factor alpha and soluble TNFRII in HIV-infected patients treated with a triple combination of stavudine, didanosine, and hydroxyurea.

TNF-alpha is involved in the pathogenesis of HIV, and is known to enhance HIV replication in vitro. In this report the kinetics of plasma TNF-alpha and sTNFRII in patients receiving aggressive antiretroviral therapy and their relationship to HIV plasma RNA and CD4 cell counts were examined. Eleven patients participating in an open label study for assessment of safety, and of virological and immunological effects of simultaneous treatment with d4T, ddI, and HU, were evaluated. The CD4 cell count of the patients before treatment ranged from 65 to 374/mm3 and their HIV plasma RNA ranged from 1.9 x 10(4) to 3.7 x 10(5) copies/ml. The viral load in eight patients decreased significantly (mean, 1.9 log10). TNF-alpha and sTNFRII plasma levels pretreatment and at 8 weeks into therapy directly correlated with HIV plasma RNA. Pretreatment circulating TNF-alpha levels of 25-114 pg/ml (mean, 56 pg/ml) decreased by more than twofold in seven patients. The change in TNF-alpha levels inversely correlated with the change in absolute CD4 cell number. Detailed kinetics of TNF-alpha and sTNFRII measured at weeks 0, 1, 2, 4, 6, 8, and 12 paralleled those of HIV plasma RNA. A rapid decline in these soluble markers was always observed at week 1 together with the HIV plasma RNA response. Three patients maintained a high viral load as well as high TNF-alpha and sTNFRII. These data suggest that (1) combination therapy with d4T, ddI, and HU decreased viral load and circulating levels of TNF-alpha/sTNFRII; (2) an association exists between the TNF-alpha/sTNFRII and HIV viral load; and (3) TNF-alpha/sTNFRII might be a useful surrogate marker for predicting efficacy of antiretroviral therapy.

Adult↗

PubMed1997

A comparative trial of zidovudine administered every four versus every twelve hours for the treatment of advanced HIV disease.

Zidovudine is approved for administration in doses given every 4 hours. Less frequent dosing has been used in many clinical trials, but the toxicity and efficacy of such regimens have not been formally compared with the approved regimen. In this multicenter, randomized, double-blind, controlled trial, the safety, tolerance and efficacy of 600 mg of zidovudine given daily in two or six divided doses were compared. Three hundred and twenty patients with a CD4 lymphocyte count < 250 cells/mm3 (mean, 104 cells/mm3) or a prior AIDS-defining illness were treated with zidovudine 100 mg every 4 hours (regimen A) or 300 mg every 12 hours (regimen B). Eighty-eight patients (56%) and 94 patients (58%), assigned to regimens A and B, respectively, completed the planned 48 weeks of treatment. Serious anemia (hemoglobin < or = 7.5 g/dl) occurred in 13% and 7% of patients treated with regimens A and B, respectively (difference, 6%, 95% confidence interval [CI], 2, 12%; p = .13). The mean duration of treatment and the frequency of neutropenia and symptomatic complaints including nausea and headache were similar in the two treatment groups. The number of patients experiencing a new opportunistic infection (18% versus 20% for regimens A and B, respectively), and the number of deaths (five in each group) did not differ significantly between groups. The effect of treatment on CD4 lymphocyte counts and HIV p24 antigenemia also was similar for both regimens. Zidovudine given at the more convenient dose of 300 mg twice daily has similar safety, and tolerance and appears to have similar efficacy to the currently approved regimen. Use of this regimen should help simplify the treatment of HIV disease.

Adult↗

PubMed1997

A relationship between the generation of burn-associated type 2 T cells and their antagonistic cells in thermally injured mice.

Anti-type 2 T cells, generated in the spleens of thermally injured mice following the appearance of burn-associated CD8+, CD11b+, TCR gamma/delta + type 2 T cells (BA2T cells), have previously been shown to improve the resistance of thermally injured mice to Herpes virus infections. Anti-type 2 T cells, CD4+, CD28+, TCR alpha/beta +, IFN-gamma-producing T cell, are able to counteract the activity of BA2T cells which have been shown to be key cells in the increased susceptibility of thermally injured mice to these infections. In the present study, part of the generation mechanisms of anti-type 2T cells was examined in mice. Anti-type 2 T cells were detected in the spleens of unburned mice 3-7 days after i.v. inoculation (2 x 10(6) cells/mouse) of BA2T cells or a BA2T cell clone, defined as T6S cells. The suppressor cell activity of T6S cells was completely inhibited when they were co-cultured with anti-type 2 T cells from mice inoculated with T6S cells. Similar phenotypic and biological profiles of anti-type 2 T cells acquired from burned mice were expressed by T6S cell-induced anti-type 2 T cells. These results indicated that anti-type 2 cells may be generated in response to the appearance of BA2T cells in thermally injured mice. Immunoregulatory circuits may be involved in the generation of anti-type 2 T cells.

Adoptive Transfer↗