SLC25A15基因复合杂合突变致HHH综合征1例报告并文献复习

目的探讨高鸟氨酸血症-高氨血症-高同型瓜氨酸尿症(HHH综合征)的临床及基因突变特点。方法回顾分析1例HHH综合征患儿的临床资料,并复习文献。结果患儿,女,2岁2个月,平素厌食高蛋白食物。生后反应弱,独走后出现共济失调,感染后加重。实验室检查示高氨血症、转氨酶升高及凝血异常。头颅MRI示半卵圆中心白质容积减少。基因检测示患儿携带SLC25A15基因c.190TC(p.Y64H)及c.278GA(p.R93Q)复合杂合突变,分别来自表型正常的父母。结论 HHH综合征临床表现以神经系统及肝脏受累为主要,需与其他尿素循环障碍及肝脏疾病相鉴别。     

COPD患者血清25羟维生素D及CRP浓度与CAT评价的关系

目的探讨COPD患者评估测试与血清25羟维生素D(25-OHD)及C反应蛋白(CRP)浓度的关系。方法 103例COPD患者根据CAT评分分为轻微、中等、严重、非常严重影响4组,测定25-OHD和CRP浓度。对经治疗后CAT评分改善1级以上的65例患者再次检测,分析变化率及与CAT改善的关系。结果各组COPD患者25-OHD值分别为21.53±6.34、13.64±2.42、11.06±4.13和9.12±3.60,严重组与非常严重组之间差异无统计学意义(P>0.05),其余各组之间差异有统计学意义(F=38.19,P<0.05);CRP值组间差异无统计学意义(P>0.05)。治疗后CAT改善的患者25-OHD水平升高,而CRP水平降低。结论 25-OHD及CRP浓度与COPD患者CAT评价有相关性,有望作为临床判断疗效的指标。     

Steroid Hormone Action in Musculoskeletal Cells Involves Membrane Receptor and Nuclear Receptor Mechanisms

Steroid hormones regulate target cells through traditional nuclear mechanisms as well as by membrane mechanisms. 1 &#102 ,25(OH) 2 D 3 and 24R,25(OH) 2 D 3 bind membrane receptors (mVDR) and mediate their effects on the physiological responses of musculoskeletal cells via protein kinase C (PKC). In cultures of costochondral growth plate chondrocytes, 1 &#102 ,25(OH) 2 D 3 binds the 1,25-mVDR in growth zone cells, activating phospholipase C (PLC), leading to diacylglycerol (DAG) production and PKC translocation to the plasma membrane. It also activates PLA 2 , increasing arachidonic acid release and prostaglandin synthesis. 24R,25(OH) 2 D 3 binds its membrane receptor in resting zone chondrocytes, activating phospholipase D (PLD), and increasing DAG and PKC activity, but translocation does not occur. PLA 2 activity is decreased, reducing arachidonic acid and prostaglandin production. 17 &#103 -Estradiol (E 2 ) activates PKC in both cartilage cells, but DAG is not involved. 1 &#102 ,25(OH) 2 D 3 and 24R,25(OH) 2 D 3 also increase PKC in osteoblasts in a cell-specific manner. Antibodies to the 1,25-mVDR block PKC activation. Membrane-mediated events influence gene expression via signaling cascades, including the ERK1/2 MAP kinases. The ability of steroid hormones to initiate events nongenomically is important for regulation of matrix vesicle (MV) function in the extracellular matrix. MVs have mVDRs, but ligand binding inhibits PKC-zeta (PKC &#145 ) via a mechanism that differs from PKC &#102 activation in the plasma membranes. Treatment of MVs from growth zone chondrocyte cultures with 1 &#102 ,25(OH) 2 D 3 releases stromelysin-1 (MMP-3) and increases TGF- &#103 activation. MMP-3 is also involved in proteoglycan degradation, facilitating calcification. 24R,25(OH) 2 D 3 inhibits PKC &#145 in MV from resting zone cell cultures and inhibits MMP-3 release. Chondrocytes and osteoblasts produce 1,25(OH) 2 D 3 , 24,25(OH) 2 D 3 , and E 2 ; thus, locally produced steroids may function as autocrine regulators of matrix events, including matrix vesicle enzyme activity and matrix protein remodelling during longitudinal growth, calcification, and growth factor activation.     

Behavioural phenotype of a patient with a de novo 1.2 Mb chromosome 4q25 microdeletion

A female patient, 20 years of age, is reported with a history characterized by developmental and psychomotor delay, and during grammar-school period increasing learning problems, ritualistic behaviours and social withdrawal. Subsequently, challenging and autistic-like behaviours became prominent. The patient showed mild facial dysmorphisms, long thin fingers with bilateral mild short V metacarpals, and hyperlaxity of the joints. Neuropsychiatric examination disclosed obsessive, ritualistic behaviours and vague ideas of reference. Neuropsychological assessment demonstrated mild intellectual disability, mental inflexibility and incongruent affect. MRI-scanning of the brain showed no relevant abnormalities. Genome wide SNP array analysis revealed a 1.2 Mb de novo interstitial microdeletion in 4q25 comprising 11 genes, that was considered to be causative for the developmental delay, perseverative cognitive phenotype and dysmorphisms.To the authors knowledge, this is the first report of a de novo 4q25 microdeletion that presents with a specific behavioural phenotype.     

Local Leaders' Perspectives on Women Veterans’ Health Care: What Would Ideal Look Like?

Background

The Veterans Health Administration (VHA) faces challenges in providing comprehensive, gender-sensitive care for women. National policies have led to important advancements, but local leadership also plays a vital role in implementing changes and operationalizing national priorities. In this article, we explore the notions of ideal women veterans' health care articulated by women's health leaders at local VHA facilities and regional networks, with the goal of identifying elements that could inform practice and policy.

Expression of CD25 is a specific and relatively sensitive marker for the Philadelphia chromosome (BCR-ABL1) translocation in pediatric B acute lymphoblastic leukemia

Background: Precursor B acute lymphoblastic leukemia (B-ALL) is the most common cancer in children and overall, has an excellent prognosis. However, the Philadelphia chromosome translocation (Ph+), t(9;22)(q34;q11), is present in a small subset of patients and confers poor outcomes. CD25 (IL-2 receptor alpha chain) expression has been associated with Ph+ B-ALL in adults, but no similar study has been performed in pediatric B-ALL. Methods: A retrospective analysis of 221 consecutive pediatric patients with a diagnosis of B-ALL (blood and/or bone marrow) from 2009 to 2012 was performed to determine an association between Ph+ B-ALL and CD25 expression. A threshold of 25% was used to define positive cases for CD25 expression by flow cytometry. Results: There were 221 patients with a diagnosis of B-ALL ranging from 2 to 22 years (median, 6 years). Eight (3.6%) B-ALL patients were positive for the Philadelphia chromosome translocation (Ph+ B-ALL) and 213 were negative (Ph-negative B-ALL). CD25 expression was observed in 6 of 8 (75%) Ph+ B-ALL patients and 6 of 213 (2.8%) Ph-negative B-ALL patients. CD25 expression was significantly higher in Ph+ B-ALL compared to Ph-negative B-ALL, with median CD25 expression of 64% (range 0-93%) and 0.1% (range 0-91%), respectively (P ≤ 0.0002). Therefore, CD25 expression as a predictor of Ph+ B-ALL had 75% sensitivity, 97% specificity, 50% positive predictive value and 99% negative predictive value. Conclusions: CD25 expression is a specific and relatively sensitive marker for the identification of Ph+ B-ALL in the pediatric population.