Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis

Introduction Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1β, tumor necrosis factor α, and interleukin-6. Methods We studied 32 outpatients (18 females; mean age: 26.2 ± 7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1β and BMD at all sites. Results In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD. Conclusions These findings may have therapeutic implications for enhancing bone density in these patients.     

Folding and function of the myelin proteins from primary sequence data.

To explain how the myelin proteins are involved in the organization and function of the myelin sheath requires knowing their molecular structures. Except for P2 basic protein of PNS myelin, however, their structures are not yet known. As an aid to predicting their molecular folding and possible functions, we have developed a FORTRAN program to analyze the primary sequence data for proteins, and have applied this to the myelin proteins in particular. In this program, propensities for the secondary structure conformations as well as physical-chemical parameters are assigned to the amino acids and the pattern of these parameters is examined by calculating their average values, autocorrelation functions and Fourier transforms. To compare two proteins, their sequences are aligned using a unitary scoring matrix, and homologies are searched by plotting a two-dimensional map of the correlation coefficients. Comparison of the corresponding myelin basic proteins (MBP) and P0 glycoproteins (P0) for rodent and shark showed that the conserved residues included most of the amino acids which were predicted to form the alpha or beta conformations, while the altered residues were mainly in the hydrophilic and turn or coil regions. In both rodent and shark the putative extracellular domain of P0 glycoprotein displayed consecutive peaks of beta propensity similar to that for the immunoglobulins, while the cytoplasmic domain showed alpha-beta-alpha folding. To trace the immunoglobulin fold along the P0 sequence, we compared the beta propensity curve of P0 with that of the immunoglobulin M603, whose three-dimensional structure has been determined. We propose that the flat beta-sheets of P0 are orientated parallel to the membrane surface to facilitate their homotypic interaction in the extracellular space. An extra beta-fold in the extracellular domain of shark P0 compared with rodent P0 was found, and this may result in a greater attraction between the apposed extracellular surfaces and may account for a smaller extracellular space as measured by x-ray diffraction. A computer search of the myelin protein sequences for functional motifs revealed sites for N-glycosylation, phosphorylation, nucleotide binding, and certain enzyme activities. We note especially that there are potential nucleotide binding sites in proteolipid protein (PLP), MBP and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). This is consistent with the experimental observations that PLP acts like an ionophore or proton channel when reconstituted into planar lipid bilayers, MBP binds GTP, and CNP catalyzes in vitro the hydrolysis of 2',3'-nucleotides into corresponding 2'-nucleotides.     

便携式负压吸引装置的设计及材料学特点

对负压吸引装置便携方式的研究一直是急救医学追求的目标之一，因为它能够极大地促进急救成功率。文章基于这种需要，研制了一套便携式负压吸引装置，并根据实际应用效果，选择优化的制造材料。研制的便携式负压吸引装置主要由特殊设计的储液罐及罐盖、负压产生装置、过渡接头等部分组成，关键部件采用特殊材料制作，体积小，质量轻，操作简单，易于携带，完全能满足临床抢救及治疗的需要。作为一种急救中必不可少的器械，便携式负压吸引装置在急救伤病员运输、转运，家庭急救，及无动力源环境等情况下，对于抢救患者及提高救治效果，具有极大的竞争优势和应用前景。     

Bone Mineral Density Determinations by Dual-Energy x-ray Absorptiometry in the Management of Patients with Marfan Syndrome—Some Factors Which Affect the Measurement

Reduced bone mineral density (BMD) was sporadically reported in patients with Marfan syndrome. This may or may not place the Marfan patient at increased risk for bone fracture. In comparing the BMDs of our patients with those reported in the literature, it seemed that agreement between values, and hence the degree of osteoporosis or osteopenia reported, was dependent on the instrumentation used. The objective of this study was to statistically assess this impression. Bone mineral density measurements from our previously published study of 30 adults with Marfan syndrome performed on a Lunar DPXL machine were compared with studies published between 1993–2000 measured using either Lunar or Hologic bone densitometry instruments. The differences of our measurements compared with those made on other Lunar machines were not statistically significant, but did differ significantly with published results from Hologic machines (P < 0.001). Before progress can be made in the assessment of BMD and fracture risk in Marfan patients and in the evidence-based orthopedic management of these patients, standardization of instrumental bone density determinations will be required along with considerations of height, obesity, age, and sex.     

螺旋CT三维重建在修复颌面部复杂骨折中的应用

目的：探讨螺旋CT三维重建在修复颌面部复杂骨折后的应用价值。方法：对50例颌面部复杂骨折患者作螺旋CT三维重建，立体直观地表现骨折的断端、部位、移位情况及骨折端与周围结构的关系等，依此准备长短大小与形态均恰当的微型钛板、钛钉，并选择合适的手术进路与手术切口。结果：通过螺旋CT三维重建，于50例清晰地显示出颌面部复杂骨折的状况，指引骨折的复位与坚强内固定术，42例牙颌功能与颌面外形获得完全恢复，8例获得基本恢复。结论：螺旋CT三维重建能较好地显示颌面部复杂骨折的三维立体解剖形态，有助于手术进路与切口的选择，和准确地实施坚强内固定术，可有效地减少外伤后颌面部的继发畸形。     

指背腱膜的解剖学研究

目的 探讨指背腱膜的构成特点及临床意义。方法 在30只成人尸体手标本上，通过模拟手术，对指背腱膜的构成特点进行了应用解剖学观测。结果 指背腱膜的构成复杂，其中的外侧腱束、外侧束、外侧腱和中央束在手指畸形的发生中有着特殊的临床意义。外侧腱束主要形成伸近节指间关节的功能解剖机制；其与外侧束形成的密切纤维联系而具有协同外侧腱的功能；该腱束与屈肌腱鞘有联系又使其具有平衡屈肌和伸肌肌力的作用。中央束在指背腱膜的整体协调、畸形的发生及矫正过程中起着重要的功能。结论 通过对指背腱膜的解剖研究，可以解释因指屈、伸肌腱平衡被破坏后所形成的畸形。     

心包疾病的CT诊断

对６１例心包疾病的ＣＴ表现进行了分析。少量心包积液主要聚集在前、左象限，中、大量积液则主要向左或左后象限扩展。根据积液厚度及分布象限可作积液量的评估。缩窄性心包炎ＣＴ均显壁层心包增厚，以心包腹侧面增厚为主，部分病人伴有心包钙化、房室扩大及腔静脉扩张。心包肿瘤侵犯或转移表现为心包不规则增厚或呈结节状改变。