Impaired natural killer activity in lymphohistiocytosis syndrome

In six patients with well-documented lymphohistiocytosis syndrome, natural killer activity was found to be profoundly impaired and could not be increased by incubation in vitro with interferon. This abnormality was not found in parents of the affected children. A clear correlation with the activity of the disease was observed, although a delay of a few weeks (possibly reflecting the life span of NK cells in blood) was seen in the disappearance of NK activity after the onset of the disease and its reappearance after remission. No absolute correlation was observed between NK activity and percentage of leukocytes detected by the Leu-7 monoclonal antibody. Our findings indicate that testing NK activity is useful for the diagnosis of lymphohistiocytosis syndrome and can be used as an index of activity of the disease, among other major clinical and biologic signs of this syndrome. Reversal of the NK activity defect (rather than detection of Leu-7 positive cells) appears to be a good criterion of complete remission.     

Impaired defense against vaccinia in a child with T-lymphocyte deficiency associated with inosine phosphorylase defect.

A case of progressive vaccinia associated with a profound deficiency of cellular immunity and a defect in inosine phosphorylase is described. A striking contrast was observed between humoral immunity, which showed little if any impairment, and a severe cellular defect affecting both markers and functions of T lymphocytes. The child died despite treatment with methosazone, levamisole, transfer factor, irradiated blood transfusions, and a thymus graft. An adequate serum level of antibody to vaccinia virus was obtained by transfer of specific immunoglobulins, but this failed to stop the progression of the disease. This observation suggests that host defense against vaccinia infection is mainly mediated by cellular immunity.     

CDw149 antibodies recognize a clustered subset of CD47 molecules associated with cytoplasmic signaling molecules

One of the recently described antigens broadly expressed on human leukocytes is CDw149, which was defined at the 6th Human Leukocyte Differentiation Antigen (HLDA) Workshop by means of 2 monoclonal antibodies (mAbs). Molecular characterization of this antigen has been lacking. In the present study we demonstrate that these anti-CDw149 mAbs actually recognize a clustered subset of a well-defined membrane protein, CD47, also known as integrin-associated protein (IAP). This clustered subset is present on leukocytes but not erythrocytes. The anti-CDw149 mAbs bind with only low affinity to a monomeric (unclustered) subset of CD47 but with high avidity to the CD47 clusters. A fraction of CD47 is associated with large complexes containing cytoplasmic signaling molecules (Src family kinases and heterotrimeric G-proteins) similar to glycosphingolipid-enriched microdomains (GEMs), which may explain the previously described signaling capacity of CD47. The low-affinity anti-CD47 mAbs may be useful tools targeting specific receptor complexes involved in cell activation. Specific reactivity of low-affinity mAbs with clustered subsets of cell surface antigens may more generally explain the nature of poorly defined "activation forms" or activation neoepitopes described previously for several cell surface molecules.     

QVA149 (indacaterol/glycopyrronium) for the treatment of chronic obstructive pulmonary disease

Introduction: The combination of two bronchodilators with different mechanisms of action to treat patients with chronic obstructive pulmonary disease (COPD) is an established medical practice, but the dissimilarities in the onset and duration of action of long-acting β₂-agonists (LABA) and long-acting muscarinic agents (LAMA) and differences in the devices used for the delivery of these drugs make free combinations uncomfortable and unpredictable, especially if focused on adherence to prescribed treatment. Therefore, there is the need for fixed-dose combinations (FDCs) of bronchodilators in a single inhaler.

Areas covered: The results of the pivotal Phase III IGNITE and EXPEDITION programs show that QVA149 (indacaterol/glycopyrronium FDC) is able to elicit a significant improvement in lung function and patient-reported outcomes, including breathlessness and rescue medication use, reduced rates of COPD exacerbations and health-related quality of life when compared with current standard of care. Moreover, QVA149 is generally well tolerated, with most adverse events being of mild-to-moderate severity.

Expert opinion: Given that the LABA/LAMA coformulation is the most powerful bronchodilator available, QVA149, which has been the first LABA/LAMA FDC to be developed, should be considered central in the maintenance treatment of COPD, and could be a potential option for improving lung function and health status in maintenance-naïve patients.     

miR-149-3p在先天性心脏病胎鼠心脏组织中的表达及其对P19细胞分化的影响

目的 探讨miR-149-3p在先天性心脏病（CHD）胎鼠心脏组织中的表达及其对小鼠畸胎瘤P19细胞分化的影响。方法 建立CHD室间隔缺损胎鼠模型,于妊娠第19天,HE染色观察心脏组织病理学变化,实时荧光定量PCR(qPCR)检测心脏组织中miR-149-3p和热休克蛋白蛋白家族B成员6(HSPB6)mRNA表达水平。二甲基亚砜（DMSO）诱导P19细胞向心肌细胞分化,并收集分化第0、5、10天的细胞,qPCR检测诱导分化过程中心肌分化标志物GATA结合蛋白4(GATA4)、心肌肌钙蛋白T(cTnT)、心房利钠尿多肽（ANP）的mRNA表达水平以及HSPB6 mRNA和miR-149-3p表达水平。miR-149-3p过表达慢病毒和空载慢病毒感染P19细胞,DMSO诱导分化第10天,免疫荧光染色检测细胞中cTnI蛋白表达情况,qPCR检测心肌分化相关标志物mRNA表达水平。双荧光素酶报告基因实验验证miR-149-3p与HSPB6之间的靶向关系。结果 与正常组比较,CHD组胎鼠出现心脏室间隔缺损,心脏组织中miR-149-3p高表达,而HSPB6低表达（P<0.01）。P19细胞...     

Empty sella of normal size in Sheehan's syndrome

This report describes the findings of computed tomography of the sella turcica region in 13 women in whom postpartum hypopltuitarism developed in the absence of a pituitary tumor. Seven patients had the typical history of severe postpartum hemorrhage (Sheehan's syndrome). Computed tomographic scanning in these patients revealed absence (in six patients) or marked reduction (in one patient) of the amount of demonstrable pituitary tissue. The pituitary fossa was occupied by material with the density of cerebrospinal fluid, resulting in the appearance of an “empty sella.” Sella size was within the normal range in six of the seven patients and enlarged in one. The six remaining patients lacked a characteristic history of vascular collapse, although several did have postpartum complications. The radiologic findings in four of these patients were similar to those seen in the patients with typical Sheehan's syndrome: one patient had a partially empty sella and another had normal results of computed tomographic scanning. Thus, 11 of 13 women with postpartum hypopituitarism were noted to have an empty or partially empty sella of normal size. This report represents the first radiologic documentation of Sheehan's syndrome as a cause of the secondary empty sella, with the characteristic finding being an empty sella of normal size.