Immunological characterization of chromogranins A and B and secretogranin II in the bovine pancreatic islet

Antisera against chromogranin A and B and secretogranin II were used for analysing the bovine pancreas by immunoblotting and immunohistochemistry. All three antigens were found in extracts of fetal pancreas by one dimensional immunoblotting. A comparison with the soluble proteins of chromaffin granules revealed that in adrenal medulla and in pancreas antigens which migrated identically in electrophoresis were present. In immunohistochemistry, chromogranin A was found in all pancreatic endocrine cell types with the exception of most pancreatic polypeptide-(PP-) producing cells. For chromogranin B, only a faint immunostaining was obtained. For secretorgranin II, A-and B-cells were faintly positive, whereas the majority of PP-cells exhibited a strong immunostaining for this antigen. These results establish that chromogranins A and B and secretogranin II are present in the endocrine pancreas, but that they exhibit a distinct cellular localization

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Reappearance of Minority K103N HIV-1 Variants after Interruption of ART Initiated during Primary HIV-1 Infection

BACKGROUND: In the Zurich Primary HIV infection study (ZPHI), minority drug-resistant HIV-1 variants were detected in some acutely HIV-1-infected patients prior to initiation of early antiretroviral therapy (ART). Here, we investigated the reappearance of minority K103N and M184V HIV-1 variants in these patients who interrupted efficient early ART after 8-27 months according to the study protocol. These mutations are key mutations conferring drug resistance to reverse transcriptase inhibitors and they belong to the most commonly transmitted drug resistance mutations. METHODOLOGY/PRINCIPAL FINDINGS: Early ART was offered to acutely HIV-1-infected patients enrolled in the longitudinal prospective ZPHI study. Six patients harboring and eleven patients not harboring drug-resistant viruses at low frequencies prior to ART were included in this substudy. Minority K103N and M184V HIV-1 variants were quantified in longitudinal plasma samples after treatment interruption by allele-specific real-time PCR. All 17 patients were infected with HIV-1 subtype B between 04/2003 and 09/2005 and received LPV/r+AZT+3TC during primary HIV-1 infection (PHI). Minority K103N HIV-1 variants reappeared after cessation of ART in two of four patients harboring this variant during PHI and even persisted in one of those patients at frequencies similar to the frequency observed prior to ART (<1%). The K103N mutation did not appear during treatment interruption in any other patient. Minority M184V HIV-1 variants were detected in two patients after ART interruption, one harboring and one not harboring these variants prior to ART. CONCLUSION: Minority K103N HIV-1 variants, present in acutely HIV-1 infected patients prior to early ART, can reappear and persist after interruption of suppressive ART containing two nucleoside/nucleotide analogue reverse transcriptase inhibitors and a ritonavir-boosted protease inhibitor. TRIAL REGISTRATION: Clinicaltrials.gov NCT00537966

Aortic root dimension changes during systole and diastole: evaluation with ECG-gated multidetector row computed tomography

Cardiac pulsatility and aortic compliance may result in aortic area and diameter changes throughout the cardiac cycle in the entire aorta. Until this moment these dynamic changes could never be established in the aortic root (aortic annulus, sinuses of Valsalva and sinotubular junction). The aim of this study was to visualize and characterize the changes in aortic root dimensions during systole and diastole with ECG-gated multidetector row computed tomography (MDCT). MDCT scans of subjects without aortic root disease were analyzed. Retrospectively, ECG-gated reconstructions at each 10% of the cardiac cycle were made and analyzed during systole (30–40%) and diastole (70–75%). Axial planes were reconstructed at three different levels of the aortic root. At each level the maximal and its perpendicular luminal dimension were measured. The mean dimensions of the total study group (n = 108, mean age 56 ± 13 years) do not show any significant difference between systole and diastole. The individual dimensions vary up to 5 mm. However, the differences range between minus 5 mm (diastolic dimension is greater than systolic dimensions) and 5 mm (vice versa). This variability is independent of gender, age, height and weight. This study demonstrated a significant individual dynamic change in the dimensions of the aortic root. These results are highly unpredictable. Most of the healthy subjects have larger systolic dimensions, however, some do have larger diastolic dimensions

Bright light treatment of depression for older adults [ISRCTN55452501]

BACKGROUND: The incidence of insomnia and depression in the elder population is significant. It is hoped that use of light treatment for this group could provide safe, economic, and effective rapid recovery. METHODS: In this home-based trial we treated depressed elderly subjects with bright white (8,500 Lux) and dim red (<10 Lux) light for one hour a day at three different times (morning, mid-wake and evening). A placebo response washout was used for the first week. Wake treatment was conducted prior to the initiation of treatment, to explore antidepressant response and the interaction with light treatment. Urine and saliva samples were collected during a 24-hour period both before and after treatment and assayed for aMT6s and melatonin respectively to observe any change in circadian timing. Subjects wore a wrist monitor to record light exposure and wrist activity. Daily log sheets and weekly mood (GDS) and physical symptom (SAFTEE) scales were administered. Each subject was given a SCID interview and each completed a mood questionnaire (SIGH-SAD-SR) before and after treatment. Also, Hamilton Depression Rating (SIGH-SAD version) interviews were conducted by a researcher who was blind to the treatment condition. A control group of healthy, age-matched, volunteers was studied for one day to obtain baseline data for comparison of actigraphy and hormone levels. RESULTS: Eighty-one volunteers, between 60 and 79 years old, completed the study. Both treatment and placebo groups experienced mood improvement. Average GDS scores improved 5 points, the Hamilton Depression Rating Scale (HDRS) 17 scores (extracted from the self-rated SIGH-SAD-SR) improved 6 points. There were no significant treatment effects or time-by-treatment interactions. No significant adverse reactions were observed in either treatment group. The assays of urine and saliva showed no significant differences between the treatment and placebo groups. The healthy control group was active earlier and slept earlier but received less light than the depressed group at baseline. CONCLUSION: Antidepressant response to bright light treatment in this age group was not statistically superior to placebo. Both treatment and placebo groups experienced a clinically significant overall improvement of 16%

Behavioural and neuroanatomical correlates of auditory speech analysis in primary progressive aphasias

Background Non-verbal auditory impairment is increasingly recognised in the primary progressive aphasias (PPAs) but its relationship to speech processing and brain substrates has not been defined. Here we addressed these issues in patients representing the non-fluent variant (nfvPPA) and semantic variant (svPPA) syndromes of PPA. Methods We studied 19 patients with PPA in relation to 19 healthy older individuals. We manipulated three key auditory parameters—temporal regularity, phonemic spectral structure and prosodic predictability (an index of fundamental information content, or entropy)—in sequences of spoken syllables. The ability of participants to process these parameters was assessed using two-alternative, forced-choice tasks and neuroanatomical associations of task performance were assessed using voxel-based morphometry of patients’ brain magnetic resonance images. Results Relative to healthy controls, both the nfvPPA and svPPA groups had impaired processing of phonemic spectral structure and signal predictability while the nfvPPA group additionally had impaired processing of temporal regularity in speech signals. Task performance correlated with standard disease severity and neurolinguistic measures. Across the patient cohort, performance on the temporal regularity task was associated with grey matter in the left supplementary motor area and right caudate, performance on the phoneme processing task was associated with grey matter in the left supramarginal gyrus, and performance on the prosodic predictability task was associated with grey matter in the right putamen. Conclusions Our findings suggest that PPA syndromes may be underpinned by more generic deficits of auditory signal analysis, with a distributed cortico-subcortical neuraoanatomical substrate extending beyond the canonical language network. This has implications for syndrome classification and biomarker development

Integration in primary community care networks (PCCNs): examination of governance, clinical, marketing, financial, and information infrastructures in a national demonstration project in Taiwan

Background. Taiwan's primary community care network (PCCN) demonstration project, funded by the Bureau of National Health Insurance on March 2003, was established to discourage hospital shopping behavior of people and drive the traditional fragmented health care providers into cooperate care models. Between 2003 and 2005, 268 PCCNs were established. This study profiled the individual members in the PCCNs to study the nature and extent to which their network infrastructures have been integrated among the members (clinics and hospitals) within individual PCCNs. Methods. The thorough questionnaire items, covering the network working infrastructures - governance, clinical, marketing, financial, and information integration in PCCNs, were developed with validity and reliability confirmed. One thousand five hundred and fifty-seven clinics that had belonged to PCCNs for more than one year, based on the 2003-2005 Taiwan Primary Community Care Network List, were surveyed by mail. Nine hundred and twenty-eight clinic members responded to the surveys giving a 59.6 % response rate. Results. Overall, the PCCNs' members had higher involvement in the governance infrastructure, which was usually viewed as the most important for establishment of core values in PCCNs' organization design and management at the early integration stage. In addition, it found that there existed a higher extent of integration of clinical, marketing, and information infrastructures among the hospital-clinic member relationship than those among clinic members within individual PCCNs. The financial infrastructure was shown the least integrated relative to other functional infrastructures at the early stage of PCCN formation. Conclusion. There was still room for better integrated partnerships, as evidenced by the great variety of relationships and differences in extent of integration in this study. In addition to provide how the network members have done for their initial work at the early stage of network forming in this study, the detailed surveyed items, the concepts proposed by the managerial and theoretical professionals, could be a guide for those health care providers who have willingness to turn their business into multi-organizations. © 2007 Lin; licensee BioMed Central Ltd.published_or_final_versio

Barrier-to-autointegration factor 1 (Banf1) regulates poly [ADP-ribose] polymerase 1 (PARP1) activity following oxidative DNA damage

The DNA repair capacity of human cells declines with age, in a process that is not clearly understood. Mutation of the nuclear envelope protein barrier-to-autointegration factor 1 (Banf1) has previously been shown to cause a human progeroid disorder, Néstor–Guillermo progeria syndrome (NGPS). The underlying links between Banf1, DNA repair and the ageing process are unknown. Here, we report that Banf1 controls the DNA damage response to oxidative stress via regulation of poly [ADP-ribose] polymerase 1 (PARP1). Specifically, oxidative lesions promote direct binding of Banf1 to PARP1, a critical NAD-dependent DNA repair protein, leading to inhibition of PARP1 auto-ADP-ribosylation and defective repair of oxidative lesions, in cells with increased Banf1. Consistent with this, cells from patients with NGPS have defective PARP1 activity and impaired repair of oxidative lesions. These data support a model whereby Banf1 is crucial to reset oxidative-stress-induced PARP1 activity. Together, these data offer insight into Banf1-regulated, PARP1-directed repair of oxidative lesions

Environmentally Realistic Exposure to the Herbicide Atrazine Alters Some Sexually Selected Traits in Male Guppies

Male mating signals, including ornaments and courtship displays, and other sexually selected traits, like male-male aggression, are largely controlled by sex hormones. Environmental pollutants, notably endocrine disrupting compounds, can interfere with the proper functioning of hormones, thereby impacting the expression of hormonally regulated traits. Atrazine, one of the most widely used herbicides, can alter sex hormone levels in exposed animals. I tested the effects of environmentally relevant atrazine exposures on mating signals and behaviors in male guppies, a sexually dimorphic freshwater fish. Prolonged atrazine exposure reduced the expression of two honest signals: the area of orange spots (ornaments) and the number of courtship displays performed. Atrazine exposure also reduced aggression towards competing males in the context of mate competition. In the wild, exposure levels vary among individuals because of differential distribution of the pollutants across habitats; hence, differently impacted males often compete for the same mates. Disrupted mating signals can reduce reproductive success as females avoid mating with perceptibly suboptimal males. Less aggressive males are at a competitive disadvantage and lose access to females. This study highlights the effects of atrazine on ecologically relevant mating signals and behaviors in exposed wildlife. Altered reproductive traits have important implications for population dynamics, evolutionary patterns, and conservation of wildlife species

Personal values and involvement in problem behaviors among Bahamian early adolescents: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Few studies, particularly in developing countries, have explored the relationship between adolescents and parental values with adolescent problem behaviors. The objectives of the study are to (1) describe adolescents' personal values, their problem behaviors, and the relationships thereof according to gender and (2) examine the relationship between parental values, adolescent values, and adolescents' problem behaviors among sixth-grade students and one of their parents.</p> <p>Methods</p> <p>The data used in these analyses were from the baseline assessment of a school-based HIV risk reduction intervention being conducted and evaluated among sixth grade students and one of their parents across 9 elementary schools in The Bahamas. Personal values were measured by the Portrait Values Questionnaire (PVQ). Seven reported problem behaviors were queried from the students, which included physical fight with a friend, drank alcohol, beer, or wine, smoked a cigarette, pushed or carried any drugs, carried a gun, knife, screwdriver or cutlass to use as a weapon, had sex and used marijuana or other illicit drugs over the past 6 months. Multilevel modeling for binary data was performed to estimate the associations between adolescent and parental values and adolescent problem behaviors.</p> <p>Results</p> <p>Among 785 students, 47% of the students reported at least one problem behavior. More boys (54%) reported having one or more problem behaviors than girls (41%, p < 0.01). Boys compared to girls expressed a higher level of self-enhancement (means score: 36.5 vs. 35.1; p = 0.03), while girls expressed a higher level of self-transcendence (42.3 vs. 40.7; p = 0.03). The results of multilevel modeling indicates that boys with a higher level of self-enhancement and girls with a higher level of openness to change and a lower level of conservation were more likely to report engagement in problem behaviors. Only two parental values (self-transcendence and conservation) were low or modestly correlated with youth' values (openness to change and self-enhancement). Parental-reported values documented limited association on adolescents' reported values and behaviors.</p> <p>Conclusion</p> <p>In designing interventions for reducing adolescents' problem behaviors, it may be important to understand the values associated with specific problem behaviors. Further exploration regarding lack of association between adolescent and parental values and problem behaviors is needed.</p