Publications

To monitor IL-4 expression at the single-cell level, we generated mice with insertions of different reporter genes into both copies of the Il4 gene that permitted the simultaneous analysis of IL-4 transcripts via GFP and IL-4 protein secretion by use of huCD2. Innate and adaptive cells competent for IL-4 production were marked by GFP, while cells that presently or recently secreted IL-4 additionally displayed huCD2. After challenge with the strictly enteric helminth, Heligmosomoides polygyrus, GFP-positive innate and adaptive cells disseminated widely, but IL-4 secretion was predominantly mediated by CD4+ T cells in the intestines and draining lymphoid organs. IL-4-competent cells persisted in cured animals, and memory responses reflected rapid cytokine production at the site of rechallenge. These data reveal a two-step process for cytokine production: the first generating poised cells that disseminate systemically and the second inducing the rapid production of the cytokine in response to local stimulation.

OBJECTIVES

We studied a sample of homeless and marginally housed adults to examine whether a history of imprisonment was associated with differences in health status, drug use, and sexual behaviors among the homeless.

METHODS

We interviewed 1426 community-based homeless and marginally housed adults. We used multivariate models to analyze factors associated with a history of imprisonment.

RESULTS

Almost one fourth of participants (23.1%) had a history of imprisonment. Models that examined lifetime substance use showed cocaine use (odds ratio [OR]=1.67; 95% confidence interval [CI]=1.04, 2.70), heroin use (OR=1.51; 95% CI=1.07, 2.12), mental illness (OR=1.41; 95% CI=1.01, 1.96), HIV infection (OR=1.69; 95% CI=1.07, 2.64), and having had more than 100 sexual partners were associated with a history of imprisonment. Models that examined recent substance use showed past-year heroin use (OR = 1.65; 95% CI = 1.14, 2.38) and methamphetamine use (OR=1.49; 95% CI=1.00, 2.21) were associated with lifetime imprisonment. Currently selling drugs also was associated with lifetime imprisonment.

CONCLUSIONS

Despite high levels of health risks among all homeless and marginally housed people, the levels among homeless former prisoners were even higher. Efforts to eradicate homelessness also must include the unmet needs of inmates who are released from prison.

OBJECTIVE

To describe tobacco industry consumer research to inform the development of more "socially acceptable" cigarette products since the 1970s.

METHODS

Analysis of previously secret tobacco industry documents.

RESULTS

28 projects to develop more socially acceptable cigarettes were identified from Philip Morris, RJ Reynolds, British American Tobacco, and Lorillard tobacco companies. Consumer research and concept testing consistently demonstrated that many smokers feel strong social pressure not to smoke, and this pressure increased with exposure to smoking restrictions. Tobacco companies attempted to develop more socially acceptable cigarettes with less visible sidestream smoke or less odour. When presented in theory, these product concepts were very attractive to important segments of the smoking population. However, almost every product developed was unacceptable in actual product tests or test markets. Smokers reported the complete elimination of secondhand smoke was necessary to satisfy non-smokers. Smokers have also been generally unwilling to sacrifice their own smoking satisfaction for the benefit of others. Many smokers prefer smoke-free environments to cigarettes that produce less secondhand smoke.

CONCLUSIONS

Concerns about secondhand smoke and clean indoor air policies have a powerful effect on the social acceptability of smoking. Historically, the tobacco industry has been unable to counter these effects by developing more socially acceptable cigarettes. These data suggest that educating smokers about the health dangers of secondhand smoke and promoting clean indoor air policies has been difficult for the tobacco industry to counter with new products, and that every effort should be made to pursue these strategies.

OBJECTIVE

To examine the predictors of transmission risk among HIV-infected men who have sex with men (MSM) in 4 US cities.

METHOD

Individual computer-assisted interviews assessing psychologic measures and sexual behavior with the 5 most recent male and female partners were conducted with a diverse sample of 1910 HIV-infected MSM recruited from community and clinic settings in San Francisco, New York, Los Angeles, and Milwaukee. Transmission-risk events were defined as unprotected vaginal or anal sex with a partner who was HIV negative or of unknown status.

RESULTS

A small but not insignificant proportion of MSM (12.7%) reported at least 1 transmission-risk event in the previous 3 months, with 57% of those events taking place with casual as opposed to steady partners. Multivariate predictors of transmission risk with casual partners were stimulant (eg, crystal methamphetamine) and other drug use, having low coping self-efficacy, and not having disclosed one's HIV serostatus to all partners. Stimulant use and failing to disclosing one's serostatus to all partners were associated with risk in primary relationships.

CONCLUSIONS

Responding to HIV transmission risk in MSM requires different strategies for primary and casual partners.

GspB and Hsa are homologous serine-rich surface glycoproteins of Streptococcus gordonii strains M99 and Challis, respectively, that mediate the binding of these organisms to platelet membrane glycoprotein (GP) Ibalpha. Both GspB and Hsa consist of an N-terminal putative signal peptide, a short serine-rich region, a region (BR) that is rich in basic amino acids, a longer serine-rich region and a C-terminal cell wall anchoring domain. To further assess the mechanisms for GspB and Hsa binding, we investigated the binding of the BRs of GspB and Hsa (expressed as glutathione S-tranferase fusion proteins) to sialylated glycoproteins in vitro. Both fusion proteins showed significant levels of binding to sialylated moieties on fetuin and GPIbalpha. In contrast, the corresponding region of a GspB homologue of Streptococcus agalactiae, which is acidic rather than basic, showed no binding to either fetuin or GPIbalpha. As measured by surface plasmon resonance kinetic analysis, GspB- and Hsa-derived fusion proteins had high affinity for GPIbalpha, but with somewhat different dissociation constants. Dot blot analysis using a panel of synthesized oligosaccharides revealed that the BR of Hsa can bind both alpha(2-3) sialyllactosamine [NeuAcalpha(2-3)Galbeta(1-4)GlcNAc] and sialyl-T antigen [NeuAcalpha(2-3)Galbeta(1-3)GalNAc], whereas the BR of GspB only bound sialyl-T antigen. Moreover, far Western blotting using platelet membrane proteins revealed that GPIbalpha is the principal receptor for GspB and Hsa on human platelets. The combined results indicate that the BRs of GspB and Hsa are the binding domains of these adhesins. However, the subsets of carbohydrate structures on GPIbalpha recognized by the binding domains appear to be different between the two proteins.

Antimicrobial stewardship programs in hospitals seek to optimize antimicrobial prescribing in order to improve individual patient care as well as reduce hospital costs and slow the spread of antimicrobial resistance. With antimicrobial resistance on the rise worldwide and few new agents in development, antimicrobial stewardship programs are more important than ever in ensuring the continued efficacy of available antimicrobials. The design of antimicrobial management programs should be based on the best current understanding of the relationship between antimicrobial use and resistance. Such programs should be administered by multidisciplinary teams composed of infectious diseases physicians, clinical pharmacists, clinical microbiologists, and infection control practitioners and should be actively supported by hospital administrators. Strategies for changing antimicrobial prescribing behavior include education of prescribers regarding proper antimicrobial usage, creation of an antimicrobial formulary with restricted prescribing of targeted agents, and review of antimicrobial prescribing with feedback to prescribers. Clinical computer systems can aid in the implementation of each of these strategies, especially as expert systems able to provide patient-specific data and suggestions at the point of care. Antibiotic rotation strategies control the prescribing process by scheduled changes of antimicrobial classes used for empirical therapy. When instituting an antimicrobial stewardship program, a hospital should tailor its choice of strategies to its needs and available resources.

BACKGROUND

Data on associations of body composition with HIV disease characteristics are limited.

OBJECTIVE

We compared sex-specific associations between HIV disease characteristics and body composition in an racially-ethnically diverse cohort of antiretroviral-naive patients.

DESIGN

The study was a cross-sectional analysis of participants enrolled in a metabolic substudy of a multicenter trial. Regional fat was measured, and total body fat (TBF) was derived by using the Durnin-Womersley formula (DWF) and bioelectrical impedance analysis (BIA). Body cell mass (BCM) was measured by BIA.

RESULTS

Among 422 participants, 22% were women, 60% were African American, and 36% had prior AIDS-defining illnesses. Mean (+/-SD) age was 38.2 +/- 9.6 y, CD4+ count was 215 +/- 184 cells/mm3, and HIV RNA log10 was 5.0 +/- 0.8 copies/mL. On multivariate analysis, women with AIDS-defining illness had significantly (P < 0.005) lower regional body fat and TBF (BIA: -9.5 kg; DWF: -7.3 kg) but nonsignificantly lower BCM (-1.3 kg) than did women without such illnesses, whereas men with AIDS-defining illness had significantly (P < 0.005) lower BCM (-1.7 kg) but nonsignificantly lower TBF (BIA: -1.3 kg; DWF: -1.83 kg) than did men without such illnesses (P < 0.05 for sex differences in TBF). Significant negative associations of HIV RNA with BCM (-0.9 kg/log RNA; P = 0.03), TBF by BIA (-1.4 kg/log RNA; P = 0.05) and by DWF (-1.6 kg/log RNA; P = 0.01), and regional fat were observed in men only.

CONCLUSIONS

The effect of prior AIDS illness on body fat differed significantly between the sexes: women with prior AIDS-defining illness had significantly less fat than did women without such illnesses. An independent effect of HIV viremia on BCM and fat was seen in men. These distinctions may be due to inherent biological differences between the sexes.