Skeletal muscle sodium channel gating in mice deficient in myotonic dystrophy protein kinase

Myotonic dystrophy, a progressive autosomal dominant disorder, is associated with an expansion of a CTG repeat tract located in the 3'-untranslated region of a serine/threonine protein kinase, DMPK. DMPK modulates skeletal muscle Na channels in vitro, and thus we hypothesized that mice deficient in DMPK would have altered muscle Na channel gating. We measured macroscopic and single channel Na currents from cell-attached patches of skeletal myocytes from mice heterozygous (DMPK(+/-)) and homozygous (DMPK(-/-)) for DMPK loss. In DMPK(-/-) myocytes, Na current amplitude was reduced because of reduced channel number. Single channel recordings revealed Na channel reopenings, similar to the gating abnormality of human myotonic muscular dystrophy (DM), which resulted in a plateau of Na current. The gating abnormality deteriorated with increasing age. In DMPK(+/-) muscle there was reduced Na current amplitude and increased Na channel reopenings identical to those in DMPK(-/-) muscle. Thus, these mouse models of complete and partial DMPK deficiency reproduce the Na channel abnormality of the human disease, providing direct evidence that DMPK deficiency underlies the Na channel abnormality in DM.     

碱性成纤维细胞生长因子与卵巢癌的关系

目的　探讨碱性成纤维细胞生长因子 (basic fibroblast growth factor,b FGF)对卵巢癌细胞增殖、浸润和肿瘤血管生成的影响 ,及 b FGF单克隆抗体 (b FGF monoclonal antibody,b FGF- MAb)的治疗作用。　方法　将人卵巢癌细胞株 SKOV3接种于 2 4孔板 ,加入不同浓度的 b FGF,每日行结晶紫染色后测定光密度 (D4 90 )值 ,绘制细胞生长曲线 ;将 SKOV3细胞团接种于铺设有细胞外基质凝胶的 4孔板 ,每日测定癌细胞在凝胶中的浸润距离 ;建立 SKOV3细胞裸鼠皮下移植瘤模型 ,每周两次分别将 b FGF、b FGF-MAb和生理盐水注射于移植瘤周围 ,8周后测量肿瘤体积 ;对移植瘤组织切片行 因子的免疫组化染色、测定肿瘤内微血管密度 (microvessel density,MVD)。　结果　 b FGF能促进 SKOV3细胞增殖并呈浓度依赖 ,实验第 5天 ,5 ng/ml、10 ng/ml组细胞 D4 90 值是对照组的 1.0 9倍和 1.2 1倍 ;b FGF能促进 SKOV3细胞浸润并呈浓度依赖 (P<0 .0 5 ) ,第 7天 ,5 ng/ml、10 ng/ml组细胞浸润距离分别是对照组的 1.5 3倍和2 .4 5倍 ;b FGF组移植瘤体积和 MVD分别是对照组的 1.80倍和 1.4 6倍 (P<0 .0 5 ) ,b FGF- MAb组移植瘤体积和 MVD分别是对照组的 6 3.7%和 6 2 .8% (P<0 .0 5 )。　结论　b FGF能明显促进卵巢癌细胞的增殖、     

Morphometric evaluation of PGP9.5 and NCAM expressing nerve fibers in colonic muscle of patients with Hirschsprung's disease

A quantitative assessment of the density of the protein gene product 9.5 (PGP9.5), the neural cell adhesion molecule (NCAM), and the low-affinity nerve growth factor receptor (NGFR) expressing nerve fibers in the circular muscle layer in the colon was carried out by morphometric analyses from 13 patients with Hirschsprung's disease (HD). The difference in the nerve fiber density between the ganglionic and aganglionic segments was compared by calculating the ratio of the sum of the areas occupied by positively stained nerve fibers per unit area of the muscle after immunohistochemical staining on paraffin embedded tissue sections using computer software. There was an obvious difference in the density of the PGP9.5 stained nerve fibers between the ganglionic (0.0380 +/- 0.0171) and aganglionic segments (0.0143 +/- 0.01661). The NCAM-positive nerve fibers were fewer in number than those of both the PGP9.5-positive fibers and NCAM-positive fibers, which were also markedly lower in number in the aganglionic segment (0.0066 +/- 0.0076) than in the ganglionic segment (0.0230 +/- 0.0195). Immunostaining for low-affinity NGFR revealed much fainter staining in the ganglionic and aganglionic segment without a statistically significant difference in their density. Considering the fact that PGP9.5 is a very sensitive marker for nerve fibers, the results of this study reaffirm the innervation failure of the proper muscle in HD. The decreased NCAM expression level in the aganglionic segment appears to be caused not by the selective down-regulation of NCAM expression among the nerve fibers but by a markedly reduced number of nerve fibers.     

In Vitro and In Vivo Characterization of MEMS Microneedles

Transdermal drug delivery TDD systems have many advantages but are conventionally limited by the low permeability of skin. The idea of using microneedles to painlessly penetrate the topmost impermeable stratum corneum has previously been put forward. In this paper, the fabrication of solid and hollow silicon microneedles with straight side-walls and with the following dimensions: 20–100 m in diameter and 100–150 m in length is described. In vitro tests demonstrate that with prior solid microneedle application, transdermal drug transport is significantly increased by 10–20 times, with the degree of enhancement being related to needle diameter. In vivo tests in diabetic animals, however, were unable to demonstrate any delivery of insulin through the hollow microneedles. It is proposed that two factors, microneedle length and tip sharpness, have to be improved for systemic drug delivery to be seen in vivo.     

16例染色体异常核型分析

目的与方法本文对189例自然流产、闭经、发育不全患者进行细胞遗传学检查,结果发现异常核型16例,异常核型涉及1、3、4、5、6、7、8、9、10、 15、X、Y染色体.其中平衡易位10例,性染色体异常3例,大Y染色体3例.结论染色体异常是导致流产、闭经、性发育异常的重要遗传因素,应引起临床医师的高度重视.     

SARS病人外周血T淋巴细胞的动态变化及其在发病进程和发病机理中的意义

目的 :通过研究严重急性呼吸综合征 (SevereAcuteRespiratorySyndrome,SARS)患者外周血免疫细胞的动态变化 ,探讨外周血免疫细胞在SARS发病进程中的意义 ,初步探讨SARS的发病机理 ,并为SARS的诊断和治疗提供有力的实验室依据。方法 :回顾性动态观察我院收治的已治愈SARS病例和SARS死亡病例外周血CD4 + 和CD8+ T淋巴细胞 ,评估外周血免疫细胞在SARS发病进程及预后中的作用。实验方法为流式细胞术检测和分析免疫细胞表面特异性荧光抗体标记 ,T细胞表面标志组合为CD3 CD8 CD4 5 CD4。结果 :所有治愈的SARS病人的CD4 + 和CD8+ T淋巴细胞都有不同程度的可逆性下降 ,而所有的死亡病例有不可逆性显著下降 ,直至死亡。T细胞下降程度和维持的时间与病情密切相关。普通型SARS病例最低CD4 + T淋巴细胞数为 30 5± 15 0cells μl(P <0 .0 0 1)、重型为 139± 6 9cells μl(P <0 .0 0 1) ,普通型SARS病例最低CD8+ T淋巴细胞数为 2 2 3± 89cells μl(P <0 .0 0 1)、重型为 171± 92cells μl(P <0 .0 0 1)。所有普通型病例和大部分重型病例T淋巴细胞恢复正常 ,个别重型病例低于正常或接近正常 ,恢复后普通型平均为 991± 2 86cells μl,重型平均为 5 4 5± 2 2 5cells μl。恢复时间有所不同 ,普通型平均为 17± 5天     

A new haplogroup pattern displayed in Fujian Han in China

Human Y-chromosomal binary polymorphisms have been considered to preserve the paternal genetic legacy and provide evidence on human evolution and the genetic relationships among and demographic history of different populations. To reveal the genetic origin and immigration of the Fujian Han, 13 binary markers on the Y chromosome were used to screen Fujian Han by allele-specific polymerase chain reaction. The results indicated that the M₉G marker was highly prevalent (96.20%), suggesting a significant genetic drift. In addition, M₁₂₂C frequency was only 22.78%, and M₄₅A and M₁₀₃T were default. The distinctive haplogroup frequencies (H₁, H₅, and H_6/7/8) imply that the haplogroup pattern is a relatively ancestral and interim type. Received: October 13, 2001 / Accepted: December 3, 2001     

Nutritional Assessment in Adult Patients with Dysphagia: A Scoping Review

Malnutrition negatively affects the quality of life of patients with dysphagia. Despite the need for nutritional status assessment in patients with dysphagia, standard, effective nutritional assessments are not yet available, and the identification of optimal nutritional assessment items for patients with dysphagia is inadequate. We conducted a scoping review of the use of nutritional assessment items in adult patients with oropharyngeal and esophageal dysphagia. The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched to identify articles published in English within the last 30 years. Twenty-two studies met the inclusion criteria. Seven nutritional assessment categories were identified: body mass index (BMI), nutritional screening tool, anthropometric measurements, body composition, dietary assessment, blood biomarkers, and other. BMI and albumin were more commonly assessed in adults. The Global Leadership Initiative on Malnutrition (GLIM), defining new diagnostic criteria for malnutrition, includes the categories of BMI, nutritional screening tool, anthropometric measurements, body composition, and dietary assessment as its required components, but not the blood biomarkers and the “other” categories. We recommend assessing nutritional status, including GLIM criteria, in adult patients with dysphagia. This would standardize nutritional assessments in patients with dysphagia and allow future global comparisons of the prevalence and outcomes of malnutrition, as well as of appropriate interventions.     

Longitudinal Changes in the Concentration of Major Human Milk Proteins in the First Six Months of Lactation and Their Effects on Infant Growth

Our knowledge related to human milk proteins is still limited. The present study determined the changes in multiple human milk proteins during the first six months of lactation, investigated the influencing factors of milk proteins, and explored the impact of milk proteins on infant growth. A total of 105 lactating women and their full-term infants from China were prospectively surveyed in this research. Milk samples were collected at 1–5 days, 8–14 days, 1 month, and 6 months postpartum. Concentrations of total protein and α-lactalbumin were measured in all milk samples, and concentrations of lactoferrin, osteopontin, total casein, β-casein, α_s−1 casein, and κ-casein were measured in milk from 51 individuals using ultra performance liquid chromatography coupled with mass spectrometry. The concentration of measured proteins in the milk decreased during the first six months of postpartum (p-trend < 0.001). Maternal age, mode of delivery, maternal education, and income impacted the longitudinal changes in milk proteins (p-interaction < 0.05). Concentrations of α_s−1 casein in milk were inversely associated with the weight-for-age Z-scores of the infants (1 m: r −0.29, p 0.038; 6 m: r −0.33, p 0.020). In conclusion, the concentration of proteins in milk decreased over the first six months postpartum, potentially influenced by maternal demographic and delivery factors. Milk protein composition may influence infant weights.     

检测血管紧张素转化酶在AFP阴性肝癌诊断中的价值

目的　探讨肝癌患者血清血管紧张素转化酶 (ACE)活性变化对AFP阴性肝癌 (HCC)患者诊断及鉴别诊断的价值。方法　选择经组织学 (肝穿刺 )或影像学确诊的 38例HCC患者 ,2 1例慢性肝炎患者 ,12例肝硬化患者及 2 0例正常健康对照者 ,检测血清AFP含量和ACE活性。结果　与其他良性肝病相比HCC患者血清ACE活性 ( 19.51± 4 .4 6)显著低于慢性肝炎 ( 38.35± 6.34 ,P <0 .0 1)及肝硬化患者 ( 4 7.77± 10 .59,P <0 .0 1) ,并且也低于正常人 ( 30 .0 0± 2 .92 ,P <0 .0 5)。 2 3例AFP阳性 (≥2 0 0mg/L)HCC患者中 ,其ACE活性为 ( 19.15± 4 .2 6) ,与AFP阴性患者比较差异无显著性 (P >0 .0 5)。结论　检测血清ACE活性有助于肝癌 ,尤其是合并肝硬化或AFP阴性的患者的诊断。ACE和AFP联合检测有助于提高肝癌的检出率