Bipolar cells specific for blue cones in the macaque retina.

A distinct subpopulation of bipolar cells in macaque monkey retina was labeled with antisera that recognize glycine-extended cholecystokinin precursors. The labeled bipolar cells were found throughout the retina and had dendrites contacting a subpopulation of cone pedicles and axons ramifying in the fifth stratum of the inner plexiform layer. Several lines of evidence indicate that the labeled bipolar cells are a single type despite some variations in their morphology. First, the density of perikarya and their diameters varied continuously as a function of eccentricity. Second, the positions of perikarya within the inner nuclear layer and the level at which the axons branched in the inner plexiform layer were constant at all eccentricities. Bipolar cells with similar morphology have been described previously as "blue cone bipolar cells" (Mariani, 1984b), but there was no direct evidence that this was the case. In this study, we show by light microscopy that labeled bipolar cells have dendrites ending exclusively upon presumptive blue cones labeled by Procion black dye. All blue cones were contacted by labeled bipolar cells, and virtually all bipolar cells contacted blue cones, the only exceptions being in regions where blue cones had been lost. Approximately 20% more labeled bipolar cells than blue cones were found at every eccentricity; thus, connections between blue cones and labeled bipolar cells were not strictly one to one. The mean number of cones presynaptic to each bipolar cell was 1.2, and the mean number of bipolar cells postsynaptic to each cone was 1.8. By an electron microscopic study of labeled bipolar cell dendrites, we determined that they became central elements of ribbon synapses in blue cones. Some of their ribbon synapses were unusual: in one type, a single, large labeled dendrite was postsynaptic to two or more ribbons, while in the other type, ribbons had two or more central elements. The presence of these invaginating contacts and the axonal terminals in the proximal inner plexiform layer suggest that the labeled bipolar cells depolarize to short-wavelength stimuli and function to relay information from blue cones to the inner plexiform layer. There were also other, unlabeled bipolar cell dendrites that received inputs from blue cones at basal junctions and triad-associated flat contacts, which suggests that there are additional types of bipolar cells conveying information from short-wavelength cones in the primate retina.     

Abnormalities of diastolic filling of the left ventricle associated with aging are less pronounced in exercise-trained individuals.

To determine whether exercise training has an effect on left ventricular diastolic dysfunction associated with the normal aging process, we studied a group of 20 normal healthy adult distance runners (mean miles currently run per week was 45 for an average of 15 years) and 20 normal healthy sedentary individuals (who currently walk less than 1 mile per day and are not involved in a regular exercise program) matched for age and systolic and diastolic blood pressure with the runners. Doppler echocardiographic indices of left ventricular diastolic filling were significantly different between the two groups. The exercise group when compared with the sedentary group had significantly decreased late diastolic peak filling velocity (0.51 +/- 0.11 m/sec versus 0.66 +/- 0.20 m/sec; p = 0.003), late diastolic velocity-time integral (5.2 +/- 1.5 cm versus 6.6 +/- 2.2 cm; p = 0.02), increased early-to-late peak filling velocity ratio (1.29 +/- 0.38 versus 0.96 +/- 0.24; p = 0.001), and early-to-late velocity-time integral ratio (2.08 +/- 0.51 versus 1.42 +/- 0.47; p less than 0.001). We conclude that the left ventricular diastolic dysfunction associated with "normal" aging is less pronounced in those persons who are exercise-trained.     

Acculturation and Gender: Influence on Healthy Dietary Outcomes for Latino Adolescents in California

ObjectiveExamine acculturation and gender on intention to eat a healthful diet among Latino adolescents using the Theory of Planned Behavior.DesignSecondary analysis of data set and condensed version of the Short Acculturation Scale for Hispanics (SASH).SettingData collected from 34 randomly selected high schools in San Bernardino, CA.Participants265 Latino high school adolescents.Main Outcome MeasuresEffects of acculturation and gender on variables of the Theory of Planned Behavior on intention to eat a healthful diet.AnalysisMultiple regression analysis examined acculturation/gender differences, and modifications on the prediction of intention. General linear modeling determined differences across gender and acculturation groups.ResultsFemales had stronger intention, more positive attitude, and greater subjective normative influence. Females indicated feeling healthy and looking good and males indicated good athletic performance as contributors to eating healthfully. Mother was influential for both genders, and stronger for females. Siblings were influential for less acculturated males, and friends were influential for highly acculturated females. Less acculturated adolescents had stronger intention to eat healthfully, more tolerance to give up liked food items, and more support and encouragement.Conclusions and ImplicationsProfessionals need to take into account gender and acculturation differences when making dietary recommendations for Latino adolescents.     

Use of Acyclovir for Suppression of Human Immunodeficiency Virus Infection Is Not Associated with Genotypic Evidence of Herpes Simplex Virus Type 2 Resistance to Acyclovir: Analysis of Specimens from Three Phase III Trials

Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcer disease and is a cofactor for HIV-1 acquisition and transmission. We analyzed specimens from three separate phase III trials of acyclovir (ACV) for prevention of HIV-1 acquisition and transmission to determine if failure of ACV to interrupt HIV acquisition and transmission was associated with genotypic ACV resistance. Acyclovir (400 mg twice daily) or placebo was provided to HSV-2-infected persons at risk of HIV-1 infection in the Mwanza and HPTN 039 trials and to persons dually infected with HSV-2 and HIV-1 who had an HIV-negative partner in the Partners in Prevention study. We extracted HSV DNA from genital ulcer swabs or cervicovaginal lavage fluids from 68 samples obtained from 64 participants randomized to ACV and sequenced the HSV-2 UL23 gene encoding thymidine kinase. The UL23 sequences were compared with published and unpublished data. Variants were observed in 38/1,128 (3.4%) nucleotide positions in the UL23 open reading frame, with 58% of these encoding amino acid changes. No deletions, insertions, or mutations known to be associated with resistance were detected. Thirty-one of the variants (81.5%) are newly reported, 15 of which code for amino acid changes. Overall, UL23 is highly polymorphic compared to other loci in HSV-2, but no drug resistance mutations were detected that could explain the failure to reduce HIV incidence or to prevent HIV-1 transmission in these studies.Herpes simplex virus type 2 (HSV-2) is one of the most common sexually transmitted infections. The prevalence of infection is higher in many parts of the developing world, especially in some settings in sub-Saharan Africa, where up to 75 to 80% of women may be infected by the age of 35 years (26).The standard treatment for symptomatic primary and recurrent genital herpes and for suppression of genital herpes has primarily been acyclovir (ACV), a guanosine nucleoside analogue that inhibits replication of HSV. The inactive prodrug is phosphorylated to ACV triphosphate by HSV-encoded thymidine kinase. The active ACV triphosphate then inhibits viral DNA polymerase. Thymidine kinase is encoded by the HSV UL23 gene. The frequency of ACV resistance is increased in ACV-treated, immunosuppressed individuals and may reach 5% (25). However, ACV resistance has also occasionally been documented in immunocompetent persons in both the absence and presence of ACV therapy (8, 28a). Up to 95% of clinically significant ACV resistance is caused by mutations in the UL23 gene that limit thymidine kinase enzymatic activity and thus prevent initial phosphorylation of the drug (1a). These are typically insertions or deletions of a single nucleotide in a poly(G) or poly(C) tract, leading to a frameshifted open reading frame with a carboxy-terminal nonsense polypeptide and premature termination (1a). Point mutations that prevent or reduce recognition of ACV as a substrate occur at lower frequencies (1a). Compared to the much greater understanding of human cytomegalovirus (CMV) and ganciclovir resistance, and HIV-1 and resistance to HIV antiretroviral therapy, the total database of resistance-associated HSV UL23 point mutations is small. Therefore, hot spots for ACV resistance-associated point mutations have not yet been identified in UL23 of HSV-2.Until recently, ACV therapy was used predominantly in developed countries. However, with the recognition that an increasing proportion of genital ulcers in developing countries are now caused by HSV (3), the World Health Organization has recommended that treatment for HSV now be included in first-line therapy for genital ulcer disease (32). In addition HSV-2 shares a synergic relationship with HIV, since it enhances HIV acquisition and transmission (1, 30). Suppression of HSV-2 was therefore evaluated to determine if this could be a potential strategy to reduce HIV acquisition or transmission, or both.Three phase III randomized controlled trials (RCTs) of HSV-2-suppressive therapy for the control of HIV have recently been completed in North and South America and Africa. Two of these trials, the Mwanza HSV trial and HPTN 039, examined the hypothesis that ACV (400 mg twice daily) given to HSV-2-seropositive, HIV-seronegative individuals would prevent HIV acquisition. The Mwanza HSV trial also examined the effects of ACV on the HIV and HSV genital viral load in dually HSV-2-infected, HIV-seropositive women. The third trial, the Partners in Prevention HSV/HIV Transmission Study, enrolled HIV-serodiscordant couples and examined the effect of the same regimen of ACV given to HIV/HSV-2 dually infected persons on HIV transmission to their non-HIV-infected partners. The trials found no effect of suppressive treatment with ACV on HIV acquisition or transmission (4, 4a, 31). Given these results, we conducted detailed examination of the UL23 sequence of a representative subset of HSV-2 specimens from subjects in the ACV arm. This is the first study to examine ACV resistance in developing countries in the setting of HSV-suppressive therapy.     

Histamine receptors in mammalian retinas

Mammalian retinas are innervated by histaminergic axons that originate from perikarya in the posterior hypothalamus. To identify the targets of these retinopetal axons, we localized histamine receptors (HR) in monkey and rat retinas by light and electron microscopy. In monkeys, puncta containing HR3 were found at the tips of ON-bipolar cell dendrites in cone pedicles and rod spherules, closer to the photoreceptors than the other neurotransmitter receptors. This is the first ultrastructural localization of any histamine receptor and the first direct evidence that HR3 is present on postsynaptic membranes in the central nervous system. In rat retinas, most HR1 were localized to dopaminergic amacrine cells. The differences in histamine receptor localization may reflect the differences in the activity patterns of the two species.