Bivariate genome-wide association analyses of femoral neck bone geometry and appendicular lean mass

Objective

Femoral neck geometric parameters (FNGPs), such as periosteal diameter (W), cross-sectional area (CSA), cortical thickness (CT), buckling ratio (BR), and section modulus (Z), are highly genetically correlated with body lean mass. However, the specific SNPs/genes shared by these phenotypes are largely unknown.

Methods

To identify the specific SNPs/genes shared between FNGPs and appendicular lean mass (ALM), we performed an initial bivariate genome-wide association study (GWAS) by scanning ∼690,000 SNPs in 1,627 unrelated Han Chinese adults (802 males and 825 females) and a follow-up replicate study in 2,286 unrelated US Caucasians.

Results

We identified 13 interesting SNPs that may be important for both FNGPs and ALM. Two SNPs, rs681900 located in the HK2 (hexokinase 2) gene and rs11859916 in the UMOD (uromodulin) gene, were bivariately associated with FNGPs and ALM (p = 7.58×10⁻⁶ for ALM-BR and p = 2.93×10⁻⁶ for ALM-W, respectively). The associations were then replicated in Caucasians, with corresponding p values of 0.024 for rs681900 and 0.047 for rs11859916. Meta-analyses yielded combined p values of 3.05×10⁻⁶ and 2.31×10⁻⁶ for rs681900 and rs11859916, respectively. Our findings are consistent with previous biological studies that implicated HK2 and UMOD in both FNGPs and ALM. Our study also identified a group of 11 contiguous SNPs, which spanned a region of ∼130 kb, were bivariately associated with FNGPs and ALM, with p values ranging from 3.06×10⁻⁷ to 4.60×10⁻⁶ for ALM-BR. The region contained two neighboring miRNA coding genes, MIR873 (MicroRNA873) and MIR876 (MicroRNA876).

Conclusion

Our study implicated HK2, UMOD, MIR873 and MIR876, as pleiotropic genes underlying variation of both FNGPs and ALM, thus suggesting their important functional roles in co-regulating both FNGPs and ALM.     

Sampling avian adipose tissue: assessing a nondestructive biopsy technique

ABSTRACT.   Adipose tissue samples can provide valuable information about the physiology, foraging ecology, and toxicology of birds. However, despite these varied applications, to date, no procedure for taking adipose samples from live birds has been described in detail, nor assessed for potential adverse effects. We describe a nonlethal method for collecting adipose tissue from adults and chicks of Black-legged Kittiwakes ( Rissa tridactyla ), Common Murres ( Uria aalge ), and Northern Fulmars ( Fulmarus glacialis ), and assess the short- and longer term effects of the procedure. Biopsies were carried out in the field using topical anesthetic and samples were taken from the synsacral region. Only two of 283 birds sampled (0.7%) had too little adipose tissue to be sampled successfully. Thirty-two kittiwakes were recaptured at varying intervals after the procedure (3–50 d) and the biopsy site inspected carefully. No signs of infection were observed and wounds healed completely within 6 d. Compared to birds captured for routine banding, biopsied kittiwakes showed neither greater weight loss nor reduced breeding success in the year of sampling. Similarly, recapture rates of biopsied birds in subsequent years were similar to those of individuals that had been blood sampled or banded. Our results suggest that collecting samples of adipose tissue by nondestructive biopsy has no more effect on birds than taking blood samples via syringe. Thus, we recommend nondestructive adipose tissue sampling via biopsy as an effective alternative to lethal methods in studies of wild birds.     

Secondary ion mass spectrometry (SIMS) of standards for analysis of soft biological tissue.

Gelatin films containing water-soluble salts of lithium, rubidium, strontium, or copper were analyzed by secondary ion mass spectrometry. Calcium and vanadium organometallic compounds in an epoxy resin were similarly analyzed. A linear relationship between positive secondary ion intensity and ion concentration was observed over several decades of ion concentration and at absolute concentrations as low as 1 wt ppm. These standards can be used for quantitative analysis of tissue or other biological material in epoxy resins, providing a highly sensitive method for simultaneous quantitation and localization of elements.     

Immunological analysis of acetyl-CoA carboxylase mass, tissue distribution and subunit composition.

Changes in the mass and subunit structure of liver acetyl-CoA carboxylase (ACC) accompany altered nutrition in vivo. Enzyme activity in different tissues and cell lines is also, in part, determined by variations in both total mass and ACC isoenzyme composition. ACC isoenzyme mass and hetero/homo-isoenzyme association were quantified by three sandwich e.l.i.s.a. assays, i.e. an avidin-based assay that measured total isoenzyme mass and two antibody-sandwich assays which measure polypeptide association. Results from the avidin-based assay reveal that the two major isoenzymes, of molecular mass 265 kDa (ACC 265) and 280 kDa (ACC 280), are present in markedly variable concentration in several rat and mouse tissues and in cell lines of rat and mouse origin. Hepatic ACC mass has been reported to be distributed between mitochondrial and cytosolic fractions and to undergo only a change in subcellular distribution without alteration in total mass on induction/repression of activity in vivo [Roman-Lopez, Shriver, Joseph & Alfred (1989) Biochem. J. 260, 927-930]. However, in the present study, immunoblotting and e.l.i.s.a. analysis reveals that, in rat liver, the mass of both isoenzymes is predominantly cytosolic in distribution, is markedly diminished on fasting and rises 6-8-fold on refeeding of a high-carbohydrate diet. These data support the results of several other investigations of hepatic ACC mass, and are consistent with known nutritionally altered changes in ACC mRNA content. By the two antibody-sandwich e.l.i.s.a. assays, isoenzyme complexes either composed of both ACC 280 and 265 or with multiple copies of ACC 265 are detectable in rat liver enzyme; their concentration varies independently of total ACC mass with the nutritional state of the rat, being lowest in fasting and highest on fasting/refeeding. E.l.i.s.a. analysis, applicable to crude tissue/cell extracts, provides a simple, sensitive and quantitative measurement of ACC mass and subunit composition. Its use may permit needed quantitative insight into the role of variable total ACC and isoenzyme mass and of alterations in ACC subunit composition that occur in vivo or in isolated cells in response to a variety of hormonal and nutritional influences.     

The influence of physical activity on lean mass accrual during adolescence: a longitudinal analysis.

During childhood, physical activity is likely the most important modifiable factor for the development of lean mass. However, the effects of normal growth and maturation must be controlled. To distinguish effects of physical activity from normal growth, longitudinal data are required. One hundred nine boys and one hundred thirteen girls, participating in the Saskatchewan Pediatric Bone Mineral Accrual Study, were repeatedly assessed for 6 yr. Age at entry was 8-15 yr. Stature, body mass, and physical activity were assessed biannually. Body composition was assessed annually by dual-energy X-ray absorptiometry. Physical activity was determined using the physical activity questionnaires for children and adolescence. Biological age was defined as years from age of peak height velocity. Data were analyzed using multilevel random-effects models. In boys, it was found that physical activity had a significant time-dependent effect on lean mass accrual of the total body (484.7+/-157.1 g), arms (69.6+/-27.2 g), legs (197.7+/-60.5 g), and trunk (249.1+/-91.4 g) (P<0.05). Although the physical activity effects were similar in the girls (total body: 306.9+/-96.6 g, arms: 31.4+/-15.5 g, legs: 162.9+/-40.0 g, and trunk: 119.6+/-58.2 g; P<0.05), boys for the same level of activity accrued, depending on the site, between 21 and 120% more absolute lean mass (g). In conclusion, habitual physical activity had a significant independent influence on the growth of lean body mass during adolescence, once biological maturity and stature were controlled.     

Target training: a technique for assessing self-regulation of skin temperature.

The determination of the achievement of self-regulation of hand temperature can be difficult, even with adequate baseline and control procedures. Although bidirectional training is often mentioned as a technique for thorough learning and for a convincing demonstration of temperature control, patients are sometimes unwilling or unable to lower hand temperature volitionally. This case report describes a patient who, due to failure at lowering her hand temperature, developed the target training method to convince herself of her self-regulation skill. The method may be useful in both clinical and research settings.     

Dual-energy X-ray absorptiometry lean soft tissue hydration: independent contributions of intra- and extracellular water

Dual-energy X-ray absorptiometry (DEXA) provides a measure of lean soft tissue (LST). LST hydration, often assumed to be constant, is relevant to several aspects of DEXA body composition estimates. The aims of this study were to develop a theoretical model of LST total body water (TBW) content and to examine hydration effects with empirically derived model coefficients and then to experimentally test the model's prediction that, in healthy adults, LST hydration is not constant but varies as a function of extra- and intracellular water distribution (E/I). The initial phase involved TBW/LST model development and application with empirically derived model coefficients. Model predictions were then tested in a cross-sectional study of 215 healthy adults. LST was measured by DEXA, extracellular water (ECW) by NaBr dilution, intracellular water (ICW) by whole body (40)K counting, and TBW by (2)H(2)O dilution. TBW estimates, calculated as ECW + ICW, were highly correlated with (r = 0.97, SEE = 2.1 kg, P < 0.001) and showed no significant bias compared with TBW measured by (2)H(2)O. Model-predicted TBW/LST was almost identical to experimentally derived values (means +/- SD) in the total group (0.767 vs. 0.764 +/- 0.028). LST hydration was significantly correlated with E/I (total group, r = 0.30, SEE = 0.027, P < 0.001). Although E/I increased with age (men, r = 0.48; women, r = 0.37; both P < 0.001), the association between TBW/LST and age was nonsignificant. Hydration of the DEXA-derived LST compartment is thus not constant but varies predictably with ECW and ICW distribution. This observation has implications for the accuracy of body fat measurements by DEXA and the use of TBW as a means of checking DEXA system calibration.     

Three dimensional socket preservation: a technique for soft tissue augmentation along with socket grafting

Background

A cursory review of the current socket preservation literatures well depicts the necessity of further esthetic considerations through the corrective procedures of the alveolar ridge upon and post extraction. A new technique has been described here is a rotational pedicle combined epithelialized and connective tissue graft (RPC graft) adjunct with immediate guided tissue regeneration (GBR) procedure.

Results

We reviewed this technique through a case report and discuss it??s benefit in compare to other socket preservation procedures.

Conclusion

The main advantages of RPC graft would be summarized as follows: stable primary closure during bone remodeling, saving or crating sufficient vestibular depth, making adequate keratinized gingiva on the buccal surface, and being esthetically pleasant.     

Carcinoembryonic antigen in breast-cancer tissue: a useful prognostic indicator.

Sections of breast carcinomas removed from 69 patients six to 13 years previously were examined using an immunoperoxidase technique to determine whether carcinoembryonic antigen (CEA) was present. Patients who had CEA-negative tumours had significantly higher five- and 10-year survival rates. The difference was not related to the stage of the disease, postoperative treatment, or histological type of tumour. These results suggest that immunohistological assessment of CEA in breast-cancer tissue may provide more precise prognostic information.     

计算机辅助软组织预测技术在正颌外科手术中的应用

目的:探讨计算机辅助软组织预测技术在正颌外科手术计划中的应用,构建虚拟手术仿真平台.方法:随机选择1例下颌骨前突伴颏部后缩畸形的患者,术前行头部螺旋CT扫描,获得的容积数据信息以DICOM格式导入Mimics软件进行三维重建,获到颅骨及软组织的三维数字化模型.在此虚拟模型的基础上,模拟骨组织的切割、旋转和平移等手术操作,并预测相应手术的术后软组织变化.结果:应用该颅颌面三维数字化模型,模拟LeFort Ⅰ型截骨术、双侧下颌升支矢状劈开截骨术(BSSRO)和水平截骨颏成型术.通过上颌骨前移、下颌骨后缩获得理想咬合关系,应用前移与后退的不同数据模拟手术过程,预测术后颌面软组织的改变效果,设计最佳手术方案.结论:计算机辅助软组织预测技术能够快速整合多种医学影像数据信息,直观模拟手术设计与术后效果,为正颌外科矫治牙颌面畸形制定个体化最佳手术方案提供了实用有效的技术和依据.     

Bolus technique for assessing distribution of inspired gas during tidal breathing

The washout of an insoluble tracer from the lung may be represented by a model with two ventilatory compartments representing poorly and better-ventilated regions. Using boli of a second insoluble gas delivered at a given point during inspirations of a multibreath washout test, the proportions of labeled inspired ventilation reaching the poorly and well-ventilated regions may be determined by analyzing the kinetics of the exhaled tracer. We studied eight normal subjects breathing through large-bore solenoid valves controlled to maintain tidal volume at 600 or 900 ml. Boli consisting of 15 ml of 80% He-20% O2 were delivered over 75 ms; this labeled approximately 125 ml of inspired gas. Boli were delivered after 50 ml had been inspired to mark early inspiration and after 300 ml had been inspired to mark midinspiration. Using 900-ml tidal breaths, late inspiration was marked by boli delivered at 600 ml. Subjects were studied in the seated and the supine positions. In both positions, significantly more of the early breath went to the poorly ventilated compartment. Several possible physiological mechanisms, singly or in combination, could account for these observations, but differences in dead space path length are most likely involved.     

Glass capillary columns applied to prostaglandins measurement: a useful tool for gas-chromatography mass spectrometry analysis

The difficulties to analyse prostaglandins (PG) by gas-liquid chromatography are mainly due to the lack of sensitivity of the gas-chromatograph itself (higher than 200 ng) and to the poor resolution of the packed columns. Therefore the use of glass capillary columns which has been applied with success for other biological compounds was tempting. We describe a comparison of the preparation of the columns and their use for PG analysis of standards and of human semen. A complete resolution of PG-1 from PG-2 series was achieved. The sensitivity was multiplied 100 fold with a flame ionisation detector when compared to packed columns and was equal to the one obtained with electron capture detectors without the inconveniences of this technique. The successful coupling of glass capillary columns to a mass spectrometer leads to promising results and allows profile studies of primary PG and their metabolites as seen with human semen.     

MALDI mass spectrometry for direct tissue analysis: a new tool for biomarker discovery

The direct analysis of tissue sections by MALDI mass spectrometry holds tremendous potential for biomarker discovery. This technology routinely allows many hundreds of proteins to be detected over a mass range of approximately 2000-70 000 Da while maintaining the spatial localization of the proteins detected. This technology has been applied to a wide range of tissue samples, including human glioma tissue and human lung tumor tissue. In many cases, biostatistical analyses of the resulting protein profiles revealed patterns that correlated with disease state and/or clinical endpoints. This work serves as a review of recent applications and summarizes the current state of technology.     

The impact of thickness heterogeneity on soft tissue biomechanics: a novel measurement technique and a demonstration on heart valve tissue

Biomechanics and Modeling in Mechanobiology - The mechanical properties of soft tissues are driven by their complex, heterogeneous composition and structure. Interestingly, studies of soft tissue...     

Validation of a dual energy X-ray absorptiometer: measurement of bone mass and soft tissue composition

We investigated the reproducibility of total and regional body composition measurements performed on a dual energy X-ray absorptiometer (DXA). A group of 38 women aged 21–81 (mean 52. 4) years was scanned twice with repositioning to determine intra-observer reproducibility of measurements of bone mineral density (BMD, g · cm⁻²), bone mineral content (BMC, g), lean mass (LM, kg) and fat mass (FM, kg) of the total body and of the major subregions of the body. In addition, the ability of the DXA machine to detect changes in LM and FM (simulated by placing 11.1 and 22.3 kg porcine lard on the body of 11 subjects) was examined. Coefficients of variations calculated from the root mean square averages of individual standard deviations were as follows (BMD, BMC, FM, LM): 1.4%, 1.1%, 1.4%, 1.7% (total body), 2.2%, 2.1%,-,- (head), 2.8%, 2.8%, 2.0%, 2.2% (trunk), 3.6%, 3.9%, 4.0%, 4.9% (arms), 2.7%, 1.3%, 2.6%, 2.8% (legs). Percentage fat (%fat) of exogenous lard was 81.3 (SD 3.5)% as assessed by the absorptiometer which corresponded well with the result of chemical analysis (82.8%). Estimated %fat of exogenous lard was not influenced by initial body mass or percentage body fat. Percentages of expected mean values with 11.1 kg lard placed on the body were 99.9 (SD 0.3) for body mass, 100.5 (SD 2.1) for LM, and 99.5 (SD 3.5) for FM. BMD was overestimated by 3.2% (P < 0.005) with 11.1 kg lard on the body. BMD as well as BMC increased significantly with 22.3␣kg lard on the body (P < 0.005). The results showed that BMD, BMC, LM, and FM of the total body were precisely estimated by the DXA machine used. Regional measurements were less precise. Changes in total body soft tissue composition were precisely and accurately estimated. The lard placed on the body falsely affected BMD and BMC measurements. Changes in body mass could have a similar effect. Accepted: 6 January 1997