Functional architecture of mammalian horizontal cells

In the rabbit retina, there are two kinds of horizontal cells (HCs). The A-type HC is a large axonless cell which contacts cones exclusively. The B-type HC is an axon bearing cell. While the somatic dendrites of B-type HCs also contact cones, the axon expands into an elaborately branched structure, the axon terminal (AT), which contacts a large number of rods. It is difficult to label the different HCs selectively by immunochemical methods. Therefore, we developed dye injection methods to label each type of HC. Then it was possible, (1) to describe the detailed structure of the AT (2) to identify the glutamate receptors mediating cone input to A and B-type HCs and rod input to ATs and (3) to test the hypothesis that the B-type HCs are coupled via Cx57 gap junctions. ^ To obtain well filled examples of single HCs, it was necessary to block gap junction coupling to stop the spread of Neurobiotin through the network. We used dye coupling in A-type HCs to screen a series of potential gap junction antagonists. One of these compounds, meclofenamic acid (MFA), was potent, water soluble and easily reversible. This compound may be a useful tool to manipulate gap junction coupling. ^ In the presence of MFA, Neurobiotin passed down the axon of B-type HCs to reveal the detailed structure of the AT. We observed that only one AT ending entered each rod spherule invagination. This observation was confirmed by calculation and two dye injections. ^ Glutamate is the neurotransmitter used by both rods and cones. AMPA receptors were colocalized with the dendrites of A and B-type HCs at each cone pedicle. In addition, AMPA receptors were located on the AT ending at each rod spherule. Thus rod and cone input to HCs is mediated by AMPA receptors. ^ A-type and B-type HCs may express different connexins because they have different dye-coupling properties. Recently, we found that connexin50 (Cx50) is expressed by A-type HCs. B-type HCs and B-type ATs are also independently coupled. Cx57 was expressed in the OPL and double label studies showed that Cx 57 was colocalized with the AT matrix but not with the somatic dendrites of B-type HCs. ^ In summary, we have identified a useful gap junction antagonist, MFA. There is one AT ending at each rod spherule, rods inputs to ATs is mediated by AMPA receptors and coupling in the AT matrix is mediated by Cx57. This confirms that HCs with different properties use distinct connexins. The properties of ATs described in this research are consistent. The connections and properties reported here suggest that ATs functions as rod HCs and provide a negative feedback signal to rods. ^

Factors associated with needle sharing among Black male injection drug users in Harris County, Texas

Background. Injection drug users (IDUs) are at increased risk for HIV transmission due to unique risk behaviors, such as sharing needles. In Houston, IDUs account for 18% of all HIV/AIDS cases among Black males. ^ Objectives. This analysis compared demographic, behavioral, and psychosocial characteristics of needle sharing and non-sharing IDUs in a population of Black males in Harris County, Texas. ^ Methods. Data used for this analysis were from the second IDU cycle of the National HIV Behavioral Surveillance System. This dataset included a sample of 288 Black male IDUs. Univariate and multivariate statistical analysis were performed to determine statistically significant associations of needle sharing in this population and to create a functional model to inform local HIV prevention programs. ^ Results. Half of the participants in this analysis shared needles in the past 12 months. Compared to non-sharers, sharers were more likely to be homeless (OR=3.70, p<0.01) or arrested in the past year (OR=2.31, p<0.01), inject cocaine (OR=2.07, p<0.01), report male-to-male sex in the past year (OR=6.97, p<0.01), and to exchange sex for money or drugs. Sharers were less likely than non-sharers to graduate high school (OR=0.36, p<0.01), earn $5,000 or more a year (OR=1.15, p=0.05), get needles from a medical source (OR=0.59, p=0.03), and ever test for HIV (OR=0.17, p<0.01). Sharers were more likely to report depressive symptoms (OR=3.49, p<0.01), lower scores on the family support scale (mean difference 0.41, p=0.01) and decision-making confidence scale (mean difference 0.38, p<0.01), and greater risk-taking (mean difference -0.49, p<0.01) than non-sharers. In a multivariable logistic regression, sharers were less likely to have graduated high school (OR=0.33, p<0.01) and have been tested for HIV (OR=0.12, p<0.01) and were more likely to have been arrested in the past year (OR=2.3, p<0.01), get needles from a street source (OR=3.87, p<0.01), report male-to-male sex (OR=7.01, p<0.01), and have depressive symptoms (OR=2.36, p=0.02) and increased risk-taking (OR=1.78, p=0.01). ^ Conclusions. IDUs that shared needles are different from those that did not, reporting lower socioeconomic status, increased sexual and risk behaviors, increased depressive symptoms and increased risk-taking. These findings suggest that intervention programs that also address these demographic, behavioral, and psychosocial factors may be more successful in decreasing needle sharing among this population.^

Outcomes of tuberculosis positive non-injection drug users in Harris County from October 1995 through September 2004

Background. The population-based Houston Tuberculosis Initiative (HTI) study has enrolled and gathered demographic, social, behavioral, and disease related data on more than 80% of all reported Mycobacterium Tuberculosis (MTB) cases and 90% of all culture positive patients in Houston/Harris County over a 9 year period (from October 1995-September 2004). During this time period 33% (n=1210) of HTI MTB cases have reported a history of drug use. Of those MTB cases reporting a history of drug use, a majority of them (73.6%), are non-injection drug users (NIDUs). ^ Other than HIV, drug use is the single most important risk factor for progression from latent to infectious tuberculosis (TB). In addition, drug use is associated with increased transmission of active TB, as seen by the increased number of clonally related strains or clusters (see definition on page 30) found in this population. The deregulatory effects of drug use on immune function are well documented. Associations between drug use and increased morbidity have been reported since the late 1970's. However, limited research focused on the immunological consequence of non-injection drug use and its relation to tuberculosis infection among TB patients is available. ^ Methods. TB transmission patterns, symptoms, and prevalence of co-morbidities were a focus of this project. Smoking is known to suppress Nitric Oxide (NO) production and interfere with immune function. In order to limit any possible confounding due to smoking two separate analyses were done. Non-injection drug user smokers (NIDU-S) were compared to non-drug user smokers (NDU-S) and non-injection drug user non-smokers (NIDU-NS) were compared to non-drug user non-smokers (NDU-NS) individually. Specifically proportions, chi-square p-values, and (where appropriate) odds ratios with 95% confidence intervals were calculated to assess characteristics and potential associations of co-morbidities and symptoms of TB among NIDUs HTI TB cases. ^ Results. Significant differences in demographic characteristics and risk factors were found. In addition drug users were found to have a decreased risk for cancer, diabetes mellitus, and chronic pulmonary disease. They were at increased risk of having HIV/AIDS diagnosis, liver disease, and trauma related morbidities. Drug users were more likely to have pulmonary TB disease, and a significantly increased amount of clonally related strains of TB or "clusters" were seen in both smokers and non-smoker drug users when compared to their non-drug user counterparts. Drug users are more likely to belong to print groups (clonally related TB strains with matching spoligotypes) including print one and print three and the Beijing family group, s1. Drug users were found to be no more likely to experience drug resistance to TB therapy and were likely to be cured of disease upon completion of therapy. ^ Conclusion. Drug users demographic and behavioral risk factors put them at an increased risk contracting and spreading TB disease throughout the community. Their increased levels of clustering are evidence of recent transmission and the significance of certain print groups among this population indicate the transmission is from within the social family. For these reasons a focus on this "at risk population" is critical to the success of future public health interventions. Successful completion of directly observed therapy (DOT), the tracking of TB outbreaks and incidence through molecular characterization, and increased diagnostic strategies have led to the stabilization of TB incidence in Houston, Harris County over the past 9 years and proven that the Houston Tuberculosis Initiative has played a critical role in the control and prevention of TB transmission. ^

HIV prevalence and contextual risk-factors among injection drug users in Harris County, Texas

Injection drug use is the third most frequent risk factor for new HIV infections in the United States. A dual mode of exposure: unsafe drug using practices and risky sexual behaviors underlies injection drug users' (IDUs) risk for HIV infection. This research study aims to characterize patterns of drug use and sexual behaviors and to examine the social contexts associated with risk behaviors among a sample of injection drug users. ^ This cross-sectional study includes 523 eligible injection drug users from Houston, Texas, recruited into the 2009 National HIV Behavioral Surveillance project. Three separate set of analyses were carried out. First, using latent class analysis (LCA) and maximum likelihood we identified classes of behavior describing levels of HIV risk, from nine drug and sexual behaviors. Second, eight separate multivariable regression models were built to examine the odds of reporting a given risk behavior. We constructed the most parsimonious multivariable model using a manual backward stepwise process. Third, we examined whether HIV serostatus knowledge (self-reported positive, negative, or unknown serostatus) is associated with drug use and sexual HIV risk behaviors. ^ Participants were mostly male, older, and non-Hispanic Black. Forty-two percent of our sample had behaviors putting them at high risk, 25% at moderate risk, and 33% at low risk for HIV infection. Individuals in the High-risk group had the highest probability of risky behaviors, categorized as almost always sharing needles (0.93), seldom using condoms (0.10), reporting recent exchange sex partners (0.90), and practicing anal sex (0.34). We observed that unsafe injecting practices were associated with high risk sexual behaviors. IDUs who shared needles had higher odds of having anal sex (OR=2.89, 95%CI: 1.69-4.92) and unprotected sex (OR=2.66, 95%CI: 1.38-5.10) at last sex. Additionally, homelessness was associated with needle sharing (OR=2.24, 95% CI: 1.34-3.76) and cocaine use was associated with multiple sex partners (OR=1.82, 95% CI: 1.07-3.11). Furthermore, twenty-one percent of the sample was unaware of their HIV serostatus. The three groups were not different from each other in terms of drug-use behaviors: always using a new sterile needle, or in sharing needles or drug preparation equipment. However, IDUs unaware of their HIV serostatus were 33% more likely to report having more than three sexual partners in the past 12 months; 45% more likely to report to have unprotected sex and 85% more likely to use drug and or alcohol during or before at last sex compared to HIV-positive IDUs. ^ This analysis underscores the merit of LCA approach to empirically categorize injection drug users into distinct classes and identify their risk pattern using multiple indicators and our results show considerable overlap of high risk sexual and drug use behaviors among the high-risk class members. The observed clustering pattern of drug and sexual risk behavior among this population confirms that injection drug users do not represent a homogeneous population in terms of HIV risk. These findings will help develop tailored prevention programs.^