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A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in16 vaccine recipients and two placebo recipients after the 2nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, (51)Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens. 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT) activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+) and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions. The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued development. Both HIV-specific antibody and T cell responses were induced and the magnitude of response correlated with the severity of local and systemic reactions. If potent adjuvants are necessary for subunit vaccines to induce broad and durable immune responses, careful, incremental clinical evaluation is warranted to minimize the risk of adverse events. ClinicalTrials.gov NCT00000886.

Objective To immunophenotype CD4 + and CD8 + T cell sub-populations in HIV-associated immune reconstitution inflammatory syndrome (IRIS). Design Nested case-control immunological study. Methods ART-naïve HIV-infected patients were prospectively observed for IRIS during the first 6 months of ART. Twenty-two IRIS cases and 22 ART-duration matched controls were sampled for T cell immunophenotyping. Results IRIS cases demonstrated significantly lower CD4 cell counts compared to controls (baseline: 79 versus 142, p = 0.02; enrollment: 183 versus 263, p = 0.05, respectively) with no differences in HIV RNA levels. Within CD4 + T cells, cases exhibited more of an effector memory phenotype compared to controls (40.8 versus 27.0%, p = 0.20), while controls trended towards a central memory phenotype (43.8 versus 30.8%, p = 0.07). Within CD8 + T cells, controls exhibited more central memory (13.9 versus 7.81%, p = 0.01, respectively) and effector (13.2 versus 8.8%, p = 0.04, respectively) phenotypes compared to cases, whereas cases demonstrated more terminal effectors than controls (28.8 versus 15.1%, p = 0.05). Cases demonstrated increased activation of CD8 + T cell effector memory, terminal effector, and effector subsets than controls (p = 0.04, 0.02, and 0.02, respectively). Conclusion CD4 + and CD8 + T cell subset maturational phenotypes were heterogeneous among IRIS cases and controls. However, IRIS cases demonstrated significant increases in activation of CD8 + T cell effector subpopulations.

Flow cytometry (FCM) is widely used in cancer research for diagnosis, detection of minimal residual disease, as well as immune monitoring and profiling following immunotherapy. In all these applications, the challenge is to detect extremely rare cell subsets while avoiding spurious positive events. To achieve this objective, it helps to be able to analyze FCM data using multiple markers simultaneously, since the additional information provided often helps to minimize the number of false positive and false negative events, hence increasing both sensitivity and specificity. However, with manual gating, at most two markers can be examined in a single dot plot, and a sequential strategy is often used. As the sequential strategy discards events that fall outside preceding gates at each stage, the effectiveness of the strategy is difficult to evaluate without laborious and painstaking back-gating. Model-based analysis is a promising computational technique that works using information from all marker dimensions simultaneously, and offers an alternative approach to flow analysis that can usefully complement manual gating in the design of optimal gating strategies. Results from model-based analysis will be illustrated with examples from FCM assays commonly used in cancer immunotherapy laboratories.

A dissociation between plasma human immunodeficiency virus (HIV) RNA levels and CD4+ cell counts has been reported in patients experiencing viral relapse while receiving antiretroviral therapy. This study compared patients with stable CD4+ lymphocytes during viral relapse while receiving treatment with patients who had sustained virus suppression. Plasma HIV RNA levels, lymphocyte immunophenotyping, and T cell receptor excision circle (TREC) levels were measured. Naive CD4+ lymphocyte phenotype and TREC levels were not significantly different in patients with virus suppression or in those who had relapsed. However, CD8+ lymphocyte activation, including the number and percentage of activated cells and CD38 antibody-binding capacity, was significantly elevated during viral relapse, compared with that in suppressed patients. By multivariable regression analyses, CD8+ and CD4+ lymphocyte activation were associated significantly with increasing plasma HIV RNA levels

Interleukin-2 (IL-2) can increase numbers of absolute CD4 cells in persons infected with the human immunodeficiency virus who are receiving antiretroviral therapy. Twenty-five subjects with >400/mm3 absolute CD4 cells received zidovudine and low-dose intravenous or subcutaneous IL-2 (⩽106 U/m2). Absolute CD4 cells increased significantly during IL-2 treatment, and 56% of the subjects achieved a maximal increase of ≥500 cells/mm3. A dose-response relationship favored increasing IL-2 doses, and subcutaneous delivery offered greater increases than intravenous administration. Fifteen subjects had persistent increases of ≥100 cells/mm3 6 weeks after IL-2 was discontinued. No changes occurred in delayed-type hypersensitivity or helper T cell responses to recall antigens. Cell-mediated cytotoxicities increased against Daudi cells. IL-2 was well tolerated and only 1 subject required dose reduction. Relatively low-dose IL-2 delivered by subcutaneous or intravenous routes may provide an important complement to antiretroviral therapy to increase absolute CD4 cells with the potential for less toxicity than with higher IL-2 doses.

When I first saw Ulrike Ottinger's film Johanna d'Arc of Mongolia at a film festival in 1990, I was totally captivated by its hilarious plot and sumptuous visual impact. It is an epic tale of East meets West in which a group of European women traveling on the Trans-Siberian Railroad are kidnapped by a band of Mongolian tribeswomen led by an imperious and beautiful Princess. Combining linear with nonlinear narrative structures, Ottinger intermingles erotic with exotic encounters, set against the extraordinary, vast beauty of the Mongolian landscape. As the film's title (which combines several languages) suggests, Ottinger both celebrates and problematizes the complexities of cultural encounter, as each group is repeatedly repositioned in relationship to its Other. In a film that refers to kidnap adventures, Bob Hope/Bing Crosby road movies, and National Geographic-style documentaries, the question of who is exotic, and to whom, becomes deliciously complex. Increasingly obsessed with memories of this film over the intervening years, I finally sought out Ottinger for this interview eleven years later.

In interview, the artist Ulrike Ottinger discusses her film Johanna d'Arc of Mongolia (1988; illus.). Following a summary of the plot, which involves a group of European women kidnapped by Mongolian tribeswomen while travelling on the Trans-Siberian railroad, Ottinger further defines the main characters and sections of the film, sheds light on her sources of inspiration, and outlines her stance on feminism and other theories with which her work has been associated. She also recounts her experiences of Mongolia and Mongolian nomadic people, recalling the challenges of shooting there, and of collaborating with a multilingual crew and with the Chinese authorities, and explains that she has since returned several times to make the 8-hour documentary Taiga (1992) and another film chronicling her own journey from Berlin through Odessa to Istanbul, entitled South-East Passage (2000; illus.), both of which will appear at Documenta XI in Kassel, Germany (2002).

I read with amusement Marjorie Hyer's article August 1 on the rival claims of First Baptist and Calvary Baptist to Jimmy Carter's possible attendance, because I had already sinned in my heart by coveting him as a member of National Baptist at 16th and Columbia NW.