Extension of a typology of alcohol dependence based on relative genetic and environmental loading

Mild, severe, and dyssocial subtypes of alcohol dependence, previously identified among Caucasian men from the Epidemiologic Catchment Area study, were also identified among Caucasian men and women with DSM-IV alcohol dependence from the National Longitudinal Alcohol Epidemiologic Survey (n = 2,703; 1,746 respectively). These subtypes were not identified among African American and Hispanic American men or women with DSM-IV alcohol dependence. Among Caucasians with alcohol dependence, the subtypes were characterized by differential loading on three dimensions: genetic, general environmental, and dyssocial environmental symptom scales developed in a prior twin study. The mild subtype (60% of men and 66% of women) was distinguished by low mean scores on all three scales; the dyssocial subtype (24% of men and 20% of women) by low mean genetic and general environmental scores but high mean dyssocial environmental scores; and the severe subtype (16% of men and 14% of women) by high scores on the genetic and general environmental scales. These subtypes also showed the expected distinctions in clinical characteristics. The severe subtype showed greater comorbid drug dependence and major depression, more treatment seeking, and a higher prevalence of parental alcoholism. The severe subtype also showed significantly greater genetic influence adjusted for overall severity of alcohol dependence (genetic ratio). Only the severe subtype showed a pattern of scale scores and clinical characteristics suggestive of substantial genetic influence. The present study indicates a robustness of the typology originally developed among DSM-III alcohol-dependent Caucasian men by empirical extension of the subtypes to a different sample of Caucasian men and, separately, Caucasian women. The use of this typology may aid in distinguishing between Caucasian alcohol-dependent individuals on the basis of relative genetic influence, enabling genetic, behavioral, and epidemiological investigations to reduce genetic or environmental "noise" and better focus on specific aspects of alcohol dependence.     

Effect of muscle,ageing time and modified atmosphere packaging conditions on the colour,oxidative and microbiological stability of packed beef

The objective of this study was to evaluate the influence of two different vacuum ageing times (7 and 14 days) and the impact of the modified atmosphere packaging (MAP) configuration (gas/product ratios: 0.5 and 1 and gas composition: 70% O₂ + 30% CO₂ and 40% O₂ + 30% CO₂ + 30% N₂) on the quality of fresh beef during subsequent storage at 4 °C. For this purpose, three separate experiments were performed. For each experiment, two different muscles (Longissimus dorsi and Biceps femoris) were sampled from four double‐muscled Belgian Blue beef carcasses. Next to colour, also the evolution in microbial load, pH, O₂ and CO₂ in the headspace and lipid oxidation at the meat surface were evaluated. A vacuum ageing for 14 days compared with 7 days resulted in a higher initial microbial load on the day of MAP packaging, which resulted finally in a significantly shorter shelf life. This ageing effect was less pronounced on the colour stability and lipid oxidation of the meat samples. No significant influence of the packaging configuration on any of the analysed parameters (colour, microbial load, pH and lipid oxidation at the meat surface) was observed.     

When online meets offline: A field investigation of modality switching

In order to explore the differing theoretical predictions of the cues-filtered-out perspective, SIDE model, and hyperpersonal model for online-to-offline relationships outside of the laboratory, a longitudinal survey study was conducted. Participants from a large online message board community who met up with an online acquaintance face-to-face completed surveys regarding their relationship with that individual before and after meeting their acquaintance face to face. Results indicated that the amount of communication with the online acquaintance was related to greater relation development whereas connection to the group was only related to greater individual closeness not satisfaction or predicted outcome value. In general the face-to-face meeting resulted in improved closeness, satisfaction, and predicted outcome value. An exploration for curvilinear effects as predicted by the hyperpersonal model revealed that predicted outcome value at time 1 had a curvilinear effect on closeness at time 2.     

Tuberculosis of the larynx

Laryngeal tuberculosis was diagnosed in two men, a 73-year-old man Dutch by birth and a 40-year-old one Turkish by birth. In the former patient it was probably primary tuberculosis, in the latter secondary (he had lung tuberculosis as well). The clinical picture was highly suggestive of laryngeal carcinoma in both patients. They both recovered with chemotherapy. Laryngeal tuberculosis may mimic laryngeal carcinoma. The diagnosis is based on Ziehl-Neelsen staining, culture and polymerase chain reaction (PCR) on Mycobacterium tuberculosis. Because laryngeal tuberculosis is highly infectious, the patient has to be nursed in isolation and people in his or her environment have to be screened. The response of laryngeal tuberculosis to chemotherapy is good.     

Sparse sampling for assessment of drug exposure in toxicological studies

A dose of 200 cGy of total-body irradiation (TBI) is nonlethal in dogs: Following a granulocyte nadir in the third week post-TBI, peripheral blood cell counts recover to normal values by about 5 weeks. In the context of studies on a potential role of major histocompatibility (MHC) class II antigens in the regulation of stress hematopoiesis, we tested the effect of anti-MHC class II monoclonal antibodies (mAbs) on hematologic recovery after TBI. Thirteen dogs were given 200 cGy of TBI not followed by marrow infusion. Five received no additional treatment (concurrent controls) and eight were given daily intravenous (IV) injections of anti-class II mAbs H81.9 (anti-HLA-DR; n = 6) or B1F6 (anti-HLA-DR and -DP; n = 2) at 0.6 (n = 4) or 1.2 mg/kg/d (n = 4) on days 0-4 (n = 7) or days 0-9 (n = 1). One control dog died early from an intercurrent infection and four recovered uneventfully. Dogs given mAbs after TBI showed significantly different granulocyte and platelet kinetics. The granulocyte nadir was lower (p = 0.09) and was reached later (p = 0.005), the duration of neutropenia was longer (p = 0.08), and recovery occurred later (p = 0.02) than among controls. Similarly the platelet nadir was lower (p = 0.05), thrombocytopenia lasted longer (p = 0.02), and recovery occurred later (p = 0.02) than among controls. Four of eight mAb-treated dogs died with marrow aplasia. We propose that following irradiation, HLA-DR mediated signals result in terminal differentiation in more mature hematopoietic precursors but interfere with replication or differentiation in early hematopoietic precursors. These observations suggest a role for MHC class II molecules in the regulation of stress hematopoiesis.     

Automated localization of the prostate at the time of treatment using implanted radiopaque markers: technical feasibility

PURPOSE: Prostate movement is a major consideration in the formation of target volumes for conformal radiation therapy of prostate cancer. The goal of this study was to determine the technical feasibility of using implanted radiopaque markers and digital imaging to localize the prostate at the time of treatment, thus allowing for reduction of the margin required for uncertainty in target position. METHODS AND MATERIALS: Radiopaque markers implanted around the prostate prior to treatment are visible on electronic radiographs generated with a portal imager or diagnostic imaging device. The locations of the images of these markers on the digital radiographs were automatically determined by a template-matching algorithm. The coordinates of the markers were found by projecting rays through the marker locations on orthogonal radiographs using a three-dimensional (3D) point-matching algorithm. Prostate and/or patient movement was inferred from the marker displacements. Images generated from known movements of a phantom with implanted markers were tested with this algorithm. Locations of markers from daily images of patients with implanted markers were determined by both manual and automatic techniques to determine the efficacy of automated localization on typical clinical images. RESULTS: Prostate movements can be automatically detected in a phantom using low-energy photons within 30 s after image acquisition and with a precision of better than 1 mm in translation and 1 degree in rotation (indistinguishable from the uncertainty in measuring precision). CONCLUSION: The studies show that on-line repositioning of the patient based on localization of the markers at the time of treatment is feasible, and may reduce the uncertainty in prostate location when combined with practical on-line repositioning techniques.     

Biodistribution of radiolabeled monoclonal antibody E48 IgG and F(ab'')2 in patients with head and neck cancer

The amphibian pronephros is fated to die during early development. Pronephric cells undergo apoptosis and their function is replaced by the mesonephros, which becomes the functional kidney of the adult frog. Tadpoles of the northern leopard frog, Rana pipiens, were inoculated with a Lucké tumour herpesvirus (LTV) preparation. Most of the animals developed typical Lucké renal carcinomas at metamorphosis. Fewer developed carcinomas of the pronephric cell type. A pronephric carcinoma, rescued from apoptosis by the herpesvirus, was harvested from a post-metamorphic frog. The tumour was judged to be pronephric by its anatomical location (in the anterior part of the body) and because both mesonephric kidneys were intact and tumour-free upon removal of the tumour mass. A tumour fragment was fixed for histological examination, which confirmed that the tissue was a renal carcinoma. A further fragment was subjected to short-term culture in order to produce metaphase cells for cytogenetical analysis. Based upon silverstained nucleolar organizing region numbers, 14 of 15 metaphase cells were estimated to have the diploid number (2N = 26) of chromosomes and a karyotype was constructed which did not appear to differ from that of normal cells. A single cell was estimated to be tetraploid (4N = 52). This is the first report of chromosomes of a pronephric Lucké carcinoma. LTV replicates only in tumour tissue maintained in the cold. Because the frog in this study had been maintained in the laboratory at 22 degrees C for about 10 months, no viruses would have been detectable with electron microscopy. However, the presence of Lucké herpesvirus DNA was detected in tumour homogenates by polymerase chain reaction amplification of a 1.2 kbp Hind III restriction fragment of the LTV DNA. The presence of LTV DNA provided assurance that the rescued pronephric tumour was indeed a Lucké carcinoma.     

Genetic influences in antisocial personality and drug use disorders

Small stress proteins protect against the cytotoxicity mediated by oxidative stress. The relationship between Hsp25 expression and the integrity of the actin network was studied in H2O2-treated murine L929 fibrosarcoma cells overexpressing endogenous wild-type (wt-) or non-phosphorylatable mutant (mt-) Hsp25. We show here that both proteins prevented actin network disruption induced by a 1 h treatment with 400 microM H2O2. In contrast, SB203580, a p38 MAPkinase inhibitor which suppresses Hsp25 phosphorylation, abolished the protective activity conferred by both wt- and mt-Hsp25. Hence, phosphorylation does not appear essential for Hsp25 protective activity against H2O2-induced actin disruption, and SB203580-sensitive events other than Hsp25 phosphorylation may be important for actin network regulation. Since, in L929 cells, wt- or mt-Hsp25 expression modulates intracellular glutathione levels, analyses were performed which revealed a direct correlation between glutathione and the integrity of the actin network. Moreover, laser scanning confocal immunofluorescences revealed that only a small fraction of wt- or mt-Hsp25 colocalized with actin microfilaments. Taken together, our results suggest that, in L929 cells, the protection against actin network disruption is probably a consequence of the redox change mediated by Hsp25 rather than a direct effect of this stress protein towards actin.