The transfer of CMV-specific clones of CD8+ T cells derived from the bone marrow donor is a safe and effective way to reconstitute cellular immunity against CMV after allogeneic marrow transplantation.

The introduction and expression of genes in somatic cells is an innovative therapy for correcting genetic deficiency diseases and augmenting immune function. A potential obstacle to gene therapy is the elimination of such gene-modified cells by an immune response to novel protein products of the introduced genes. We are conducting an immunotherapy trial in which individuals seropositive for human immunodeficiency virus (HIV) receive CD8+ HIV-specific cytotoxic T cells modified by retroviral transduction to express a gene permitting positive and negative selection. However, five of six subjects developed cytotoxic T-lymphocyte responses specific for the novel protein and eliminated the transduced cytotoxic T cells. The rejection of genetically modified cells by these immunocompromised hosts suggests that strategies to render gene-modified cells less susceptible to host immune surveillance will be required for successful gene therapy of immunocompetent hosts.

This study was negative for the primary end point, but findings for the secondary end points suggest that sargramostim therapy decreased disease severity and improved the quality of life in patients with active Crohn's disease.

Recognition of virus-infected cells by CD8+ cytotoxic T lymphocytes requires that the viral proteins be processed into peptides, the derived peptides transported into the endoplasmic reticulum and inserted into the binding groove of a major histocompatibility complex class I molecule, and the antigenic complex exported to the cell surface. However, viral pathogens can disrupt this process and interfere with immune recognition. These mechanisms may be vital to large viruses such as human cytomegalovirus (CMV), which causes persistent infection despite producing over 200 potentially antigenic proteins during the sequential immediate-early, early and late phases of viral gene expression. Products of CMV early-phase gene expression can globally block class I presentation and prevent recognition of infected cells by cytotoxic T lymphocytes, but an essential viral transcription factor, the 72K principal immediate-early protein, is abundantly expressed before this blockade. However, only a few host CD8+ cytotoxic T lymphocytes specific for immediate-early protein are present in seropositive individuals, and these lyse CMV-infected cells poorly. Here we demonstrate selective abrogation of immediate-early peptide presentation by a CMV matrix protein with associated kinase activity and suggest that modification of a viral protein can result in limiting access to the processing machinery and evasion of cytotoxic-T-cell recognition.

While there has been a growing concern with alcohol-related problems among Mexican Americans and an increase in research devoted to learning more about alcohol use in this population, data on these issues are widely scattered. Differences in perspectives on alcohol-related issues and variation in research methodologies have produced a body of information which must be viewed as a whole before distinct patterns can be clearly seen. These circumstances have made it difficult to apply research findings in the design of programs that would be relevant and useful to Mexican Americans suffering problems related to alcohol. Using a framework based on the foci of ethnic alcohol studies in the United States, this review provides information on modal patterns of alcohol use in Mexico, and on the prevalence and level of alcohol use among Mexican Americans. Factors affecting intra-ethnic variation in Mexican American alcohol practices, such as region, gender, age, acculturation and social class are documented. The prevalence and incidence of social and medical problems associated with excessive alcohol use in this population are summarized. Consideration is given to the role of acculturation stress in the etiology of alcohol abuse among Mexican Americans. Conceptual and methodological problems in past research are critically assessed, discontinuities in the literature identified, and areas in particular need of research are delineated.

Using data from a re-analysis of a 1976 survey of alcohol patterns among Latinos in California as a basis of comparison this article summarizes what is known about the drinking practices of immigrant Mexican women. Immigrant Mexican women's alcohol-related practices are compared with those of women in several pertinent groups: Mexicans in Mexico, other U.S. Latinas and, most particularly, later generation Mexican American women. Immigrant women s drinking is also contrasted with that of their male counterparts. Evidence that increased drinking among U.S.-born women of Mexican heritage takes place in a context of culture change and acculturation is reviewed. Finally, changes in the direction of greater permissiveness and rationalization of alcohol use among later generationi Mexican American women are demonstrated.

Protection from cytomegalovirus (CMV) disease in immunocompromised hosts has been shown to correlate with recovery of the host virus- specific CD8+ T-cell response. The administration of ganciclovir to immunosuppressed transplant recipients as antiviral prophylaxis has reduced the early risk of CMV disease, but late disease is observed with increased frequency, suggesting that recovery of the CMV-specific T-cell responses necessary for protective immunity may be delayed in these patients. Therefore, we evaluated reconstitution of CMV-specific T-cell responses in 47 bone marrow transplant (BMT) recipients entered on a randomized placebo-controlled study of ganciclovir. The study drug was initiated at a mean of 24 days after BMT. At day 30 to 40, a minority of patients had recovery of T-cell immunity to CMV and the frequency of reconstitution was equivalent in patients randomized to ganciclovir or placebo. The failure of ganciclovir to effect early reconstitution may reflect the short duration of treatment. Early recovery was associated with the infusion of BM from a CMV seropositive donor (P = .07 for CD8+ cytotoxic T cell (CTL), P = .04 for CD4+ Th). Between day 40 and day 90, recovery of deficient CD8+ and CD4+ CMV- specific T-cell responses occurred in the majority of individuals that received placebo, but in a minority of ganciclovir recipients. Two cases of late-onset CMV disease occurred in ganciclovir recipients. In all patients, the presence of a CTL response to CMV conferred protection from subsequent CMV disease (P = .005), and these protective CTL responses are shown to be specific for structural virion proteins similar to the responses in immunocompetent CMV seropositive individuals. These data confirm the importance of CMV-specific T-cell responses and suggest that a delay in recovery of these responses as a result of ganciclovir prophylaxis may contribute to the occurrence of late CMV disease.

Adverse effects from BZP commonly include confusion, agitation, vomiting, anxiety, and palpitations. There is strong evidence that higher plasma levels of BZP are associated with an increased incidence of seizures. Co-ingestion of ethanol increases the likelihood of common and distressing BZP-induced symptoms but reduces the incidence of BZP seizures.