Heritability of body composition measured by DXA in the diabetes heart study

OBJECTIVE: The purpose of this study was to investigate the heritability of body composition measured by DXA in the Diabetes Heart Study (DHS). RESEARCH METHODS AND PROCEDURES: Participants were 292 women and 262 men (age, 38 to 86 years; BMI, 17 to 57 kg/m(2)) from 244 families. There were 492 white and 49 African-American sibling pairs. DXA measurements of percentage fat mass (FM), whole body FM, and lean mass (LM), as well as regional measurements of trunk fat mass (TFM) and appendicular lean mass (ALM), were obtained. Heritability of FM, LM, and BMI were estimated using Sequential Oligogenic Linkage Analysis Routines. RESULTS: After adjusting for age, gender, ethnicity, and height, the heritability estimates of various compositional attributes were %FM = 0.64, whole body FM = 0.71, TFM = 0.63, whole body LM = 0.60, ALM = 0.66, and BMI = 0.64 (all p < 0.0001). Additional adjustment for diabetes status, smoking, dietary intake, and physical activity resulted in only minor changes in the heritability estimates (h(2) = 0.63 to 0.72, all p < 0.0001). Furthermore, heritability of TFM after additional adjustment for whole body FM was significant (h(2) = 0.55, p < 0.0001), and heritability of ALM after additional adjustment for whole body LM was also significant (h(2) = 0.51, p < 0.0001). DISCUSSION: These data suggest that FM and LM measured by DXA are highly heritable and can be effectively used in designing linkage studies to locate genes governing body composition. In addition, regional distribution of FM and LM may be genetically determined.     

Detection of base damage in DNA in human blood exposed to ionizing radiation at biologically relevant doses.

The alkaline elution technique for the detection of DNA damage has been adapted to allow application on unlabelled blood cells. Both the induction and subsequent repair have been studied of two classes of DNA damage, viz, single-strand breaks and base damage recognized by the gamma-endonuclease activity in a cell-free extract of Micrococcus luteus bacteria. The high sensitivity of the assay permitted the measurement of induction and repair of base damage after in vitro exposure of full blood under aerobic conditions to biologically relevant doses of gamma-rays (1.5-4.5 Gy). After a radiation dose of 3 Gy about 50% of the base damage was removed within 1.5 h of repair. Base damage could still be detected at 24 h after exposure to 15 Gy.     

Mixed lymphocyte reactivity and cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes in C57BL/10 congenic and B10.A recombinant mouse strains

Cell-mediated lympholysis (CML) to trinitrophenyl (TNP)-modified autologous splenic lymphocytes has been recently reported in the mouse (1). Both the sensitization and effector phases of this phenomenon were shown to be T-cell mediated. Effector cell specificity studies indicated that modification of the target cells is a necessary but insufficient requirement for cytolysis, and suggested that altered cell surface components controlled by genes mapping in the mouse major histocompatibility H-2 complex (MHC) are important in the specificity of the cytotoxic reaction (1). In allogeneic models the generation of cytotoxic effector cells has been shown to be preceded or accompanied by immunogen- induced proliferation of responding lymphocytes, i.e. a mixed lymphocyte reaction (MLR) (2-5), although the generation of effectors may not necessarily always be the consequence of extensive cell proliferation (5). If the induction of cytotoxic effector lymphocytes by modified syngeneic spleen cells is characteristic of sensitization with cellular alloantigens, one would expect to find that sensitization with TNP-modified autologous cells would also induce thymidine incorporation by the responding cells in the culture. The present report demonstrates that both stimulation of thymidine incorporation and generation of cytotoxic effector cells are part of the in vitro response to TNP-modified autologous lymphocytes. However, the MLR to TNP- modified autologous cells consistently appeared to be less pronounced when compared with an allogeneic MLR, whereas the cytotoxic activity of the effector cells generated by sensitization against TNP-modified autologous cells was frequently as high as that detected against H-2 alloantigens. These two components of reactivity to “modified self” are verified in several C57BL/10 congenic and B10.A recombinant mouse strains.     

青少年和成年人无症状阻生智齿干预措施的疗效评价

目的评价在青少年和成人中拔除与保留无症状阻生智齿的效果.方法计算机检索Cochrane口腔健康组资料库(至2004年8月4日),Cochrane中心临床对照试验资料库(CENTRAL),Ovid-MEDLINE(1966～2004年8月4日),PubMed(1966～2004年8月4日)和EMBASE(1974～2004年8月4日).检索无语种限制.同时对主要相关杂志进行手检,并尽力获取正在进行和未发表的研究.纳入比较预防性拔除与保留阻生智齿效果的全部随机对照或临床对照研究.由3位作者分别独立评价所检出文献的相关性、真实性并提取数据,如有不确定性,联系作者以获取关于随机和失访的更多信息.对所有试验均进行了质量评价.结果共纳入3个研究,其中2个已完成的随机对照试验评价了青少年预防性拔除智齿对切牙拥挤的影响,另1个随机对照试验正在进行,但研究者不能提供任何资料,他们准备近期发表文章,如是,其资料将被纳入本评价的更新中.已完成的2个研究结局判断指标不同,不能进行数据合并.结论没有证据支持或反对常规预防性拔除成年人无症状阻生智齿,有一些可靠的证据表明在青少年预防性拔除阻生智齿既不能减少也不能预防切牙拥挤.     

Efficacy,safety and tolerability of green tea catechins in the treatment of external anogenital warts: a systematic review and meta‐analysis

Background External anogenital warts (EGWs) are non‐malignant skin tumours caused by human papillomavirus. They are one of the fastest growing sexually transmitted diseases. Current treatments are unsatisfactory. Green tea sinecatechin Polyphenon E ointment is a botanical extract from green tea leaves exhibiting anti‐oxidant, anti‐viral and anti‐tumour properties. Objective The aim of this study was to integrate valid information and provide basis for rational decision making regarding efficacy and safety of green tea extracts in the treatment of EGWs. Methods A systematic search in electronic databases was conducted using specific key terms. Main search was performed independently by two reviewers. The accumulated relevant literature was subsequently systematically reviewed and a meta‐analysis was conducted. Results Three randomized, double‐blind, placebo‐controlled studies evaluating efficacy and safety of Polyphenon E 15% and 10% in the treatment of warts were included in the systematic review and meta‐analysis. A total of 660 men and 587 women were enrolled. Regarding primary outcome, both Polyphenon E 15% and 10% demonstrated significantly higher likelihood of complete clearance of baseline and baseline and new warts compared with controls. No significant heterogeneity was detected. Recurrence rates were very low. Commonest local skin sign was erythema and local skin symptom was itching. Conclusions Efficacy of Polyphenon 15% and 10%, at least for the primary endpoint, is clearly indicated. Polyphenon E treatment exhibits very low recurrence rates and appears to have a rather favourable safety and tolerability profile. Recommendations for future studies should include evaluation of the efficacy of green tea catechins in the treatment of internal anogenital warts and direct comparison with its principal comparator, imiquimod.     

Investigation of cytokine levels and their association with SCORAD index in adults with acute atopic dermatitis

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing frequency over the last decades, especially in adults. Cytokines orchestrate atopic skin inflammation. Objectives The aim of this study was to compare serum levels of cytokines in adult patients with acute AD (AD1) with other groups of AD patients and controls and investigate the possible association between such cytokines and disease severity. Methods We measured cytokine levels using flow cytometry in 21 adult patients with acute AD, 12 adults with chronic AD, 10 children with acute AD and 10 healthy adults. Results Flow cytometry analysis of cytokines revealed that interleukin 10 (IL‐10), IL‐6, interferon γ (IFN‐γ) and IL‐4 levels were significantly decreased in AD1 group compared with controls, whereas IL‐2 and tumour necrosis factor (TNF) did not differ. Comparison of AD1 group with adults chronic phase group showed that IgE, eosinophil and IL‐2 levels remained unaltered, whereas IL‐10, IL‐6, IFN‐γ, IL‐4 and TNF were significantly decreased. SCORAD and IgE levels were significantly increased, IL‐10, IL‐6 and IFN‐γ were decreased and TNF, IL‐2, IL‐4 and eosinophil levels remained unchanged in AD1 group compared with children acute phase group. Within AD1 group correlation analysis revealed that IgE and TNF levels were significantly associated with AD severity. Coefficient of determination analysis revealed that TNF and IgE levels could explain 49.14% and 35.28% of the variance of SCORAD. Conclusions These data indicate that serum IgE and TNF levels correlate with AD severity and that serum cytokines are downregulated in AD1 group. Further studies are clearly needed to elucidate cytokines’ role in adults with AD .     

Primary projections and efferent cells of the VIIIth cranial nerve in the monitor lizard, Varanus exanthematicus

In order to describe the central relations of both the afferent and efferent components of the VIIIth cranial nerve in one reptile, the methods of anterograde and retrograde axonal transport and anterograde degeneration were used to study the vestibular and cochlear projections and the efferent system of this nerve in Varanus exanthematicus. On the basis of cresyl violet and Klüver-Barrera staining, five vestibular nuclei, four cochlear nuclei, and two clusters of small cells which could not be designated as strictly auditory or vestibular are distinguished. The vestibular nuclei include the nucleus dorsolateralis, nucleus ventrolateralis, nucleus tangentialis, nucleus ventromedialis, and nucleus descendens. The well-developed cochlear nuclear complex includes the nucleus angularis, nuclei magnocellulares medialis and lateralis, and nucleus laminaris. The two cell clusters are located dorsolaterally in the brainstem just ventrolateral to the acoustic tubercle. The primary afferent vestibular fibers coursing in the anterior VIIIth nerve root distribute to the ventral portions of all vestibular nuclei except nucleus ventromedialis, whereas the fibers coursing in the posterior root project to the dorsal portions of these nuclei. In nucleus ventromedialis fibers of both roots do not segregate into ventral and dorsal portions. Other targets of the vestibular fibers are the two cell clusters, the granular layer of the ipsilateral cerebellum, the reticular formation, and the descending trigeminal tract and its nucleus. The primary cochlear fibers coursing in the posterior root terminate in nucleus angularis, nuclei magnocellulares medialis and lateralis, and the inner cell strand of nucleus laminaris. The efferent system is, ipsi- and contralaterally in the brainstem, composed of ventral and dorsal cell groups that extend from the level of the principal abducens nucleus caudally where they overlap with the facial motor nucleus. The fibers, which originate from the contralaterally located efferent cells, course beneath the IVth ventricle to exit the brainstem on the ipsilateral side.     

Heritability of Spinal Trabecular Volumetric Bone Mineral Density Measured by QCT in the Diabetes Heart Study

The heritability of trabecular volumetric bone mineral density (BMD) determined by quantitative computed tomography (QCT) has not yet been reported. The purpose of this study was to investigate the heritability of BMD as determined by QCT and DXA in 124 women and 120 men (age 39–83 years, BMI 17–75, 84% type 2 diabetics) from 101 families (232 sibling pairs) in the Diabetes Heart Study. Volumetric BMD had a heritability (h²) estimate of 0.73 (SE = 0.15, P < 0.0001) at the lumbar spine and 0.71 (SE = 0.15, P < 0.0001) at the thoracic spine. Areal BMD heritability estimates were 0.56 for PA spine, 0.43 for total hip, 0.43 for femoral neck, 0.45 for distal radius, 0.42 for mid-radius, and 0.52 for whole body (all P < 0.01). After accounting for familial correlation using generalized estimating equations, volumetric BMD was inversely associated with age (r = –0.52, P < 0.0001) and duration of diabetes (r = –0.24, P < 0.01) and positively associated with body weight (r = 0.25, P < 0.01). In multivariate analysis, adjustment for age, sex, and race lowered the h² estimates for volumetric BMD at the lumbar (h² = 0.41, P < 0.01) and thoracic (h² = 0.48, P < 0.001) spine, increased the h² estimate for areal BMD at the mid radius (h² = 0.58, P < 0.0001), and had little effect on the h² estimate for areal BMD at other sites (h² = 0.41–0.55, all P < 0.01). Additional adjustment for BMI, duration of diabetes, and physical activity had little effect on the h² estimates for volumetric BMD or areal BMD except at the hip where they were lowered (h² = 0.31–0.33, all P < 0.05). These data suggest that, like areal BMD, volumetric BMD is highly heritable and may be used in designing linkage studies to locate genes governing bone metabolism.