Prothrombin complex proteins as cofactors in platelet aggregation. I. Inhibition of aggregation by antiserum

Data are presented to support the concept that the vitamin K-dependent coagulation factors are adsorbed onto the platelet membrane and that these make up part of the "plasma atmosphere" necessary for the aggregation of platelets by various agents. Together with evidence that other coagulation factors also are part of the plasma atmosphere, it is suggested that the aggregation reaction is part of the coagulation sequence. The immunologic approach to demonstrating constituents of the platelet membrane promises to be a highly specific technique for studying further the constituents of the platelet membrane and their reactions in hemostasis.     

The polyadenylation site mutation in the alpha-globin gene cluster

In a previous study, we described a form of nondeletion alpha- thalassemia (alpha T Saudi alpha) found in subjects of Saudi Arabian origin. In the current study, using synthetic oligoprobe hybridization and restriction enzyme analysis, we have demonstrated that the molecular basis of alpha T Saudi alpha is due solely to a single base mutation (AATAAA----AATAAG) in the polyadenylation signal of the alpha 2 gene and that the frameshift mutation in codon 14 of the linked alpha 1 gene is the result of a cloning artefact. The alpha 2 polyadenylation signal mutation occurs in other Middle Eastern and the Mediterranean populations and is responsible for the clinical phenotype of Hb H disease in some Saudi Arabian individuals with five alpha genes (alpha T Saudi alpha/(alpha alpha alpha)T Saudi). Evidence suggests that the (alpha alpha alpha)T Saudi haplotype has arisen as a result of a recombination between two misaligned chromosomes bearing the alpha T Saudi alpha defect.     

Modulation of murine granulocyte proliferation in diffusion chamber cultures

Normal mouse marrow cells were cultured in Millipore diffusion chambers for long periods of time and at a variety of cell concentrations. All cultures showed a pattern of granulocyte proliferation characterized by logarithmic growth followed by prolonged stabilization of cell number starting a 7 days thereafter. The height of this "plateau" varied in relationship to the level of cell input and characteristically was far lower than the maximum cell density that can be maintained in this culture system. Additional studies showed that the plateau represented a steady state of granulocyte turnover and was not due to alterations in the diffusion chambers or the host mice. Regulatory mechanisms intrinsic to the cultured cell population appeared to play a primary role in maintaining this stable plateau. Modulation of granulocyte proliferation was partly due to increasing cell density; particularly with high input concentrations. In addition, differential cell counts suggested that critical changes in the relationship between immature and mature granulocytes partially accounted for this apparent autoregulation of cell growth. The plateau period in diffusion chamber cultures in many ways resembles granulocyte proliferation in normal mouse bone marrow and is a useful model for the study of regulatory functions in granulocytopoiesis.     

Antithrombin "Chicago": a functionally abnormal molecule with increased heparin affinity causing familial thrombophilia

A family with a high incidence of spontaneous thromboembolism over four generations has been investigated. The propositus is a 21-yr-old male with a history of thrombophlebitis. Medical histories of 46 family members were obtained. Twelve of these individuals have experienced deep venous thromboses and/or pulmonary emboli. Seven members of the kindred, with a prior history of thrombotic phenomena, were investigated in detail. These subjects were found to have normal plasma concentrations of immunoreactive antithrombin (mean 96%), decreased plasma levels of progressive antithrombin activity (mean 50%), and greatly reduced amounts of plasma heparin cofactor activity (mean 42%). The abnormal antithrombin ("Chicago") was found to elute from heparin- Sepharose at a higher ionic strength than normal inhibitor. The functionally defective antithrombin molecules exhibit a reduced ability to neutralize thrombin in the presence or absence of heparin (approximately 10%-20% of normal). The molecular defect of this protease inhibitor thus appears to be distinct from those of previously described abnormal antithrombins.     

ADA与EASD对2型糖尿病高血糖处理：治疗启动与评定的新共识方案

在不到一年时间由同一批专家代表ADA和EASD先后起草和发布了两次关于“2型糖尿病高血糖处理的共识声明”同时发表在2008年1月和12月的《DiabetesCare》和《Diabetologia》上。第一次共识声明内容主要围绕TZDs药物的安全性,本刊作了摘译转载（参阅《中国糖尿病杂志22008年第7期）。第二次修订的共识声明,关注点为降糖药的新分级,论据及观点比较清晰,故仍摘译供读者参考。     

Autoimmune polyglandular syndrome Type 3 and growth hormone deficiency

Quintos JB, Grover M, Boney CM, Salas M. Autoimmune polyglandular syndrome type 3 and growth hormone deficiency. The simultaneous occurrence of prepubertal Graves' disease, type 1 Diabetes Mellitus (DM), and Growth hormone deficiency (GHD) is uncommon. GHD has been reported in Autoimmune Polyglandular Syndrome (APS) Type 1 and Type 2 but not in APS Type 3. We report a 3‐yr‐old boy who presented simultaneously with type 1 DM and Graves' disease. After he developed urticarial rash to Propylthiouracil and Methimazole with persistent thyrotoxicosis, he received 8 millicuries of ¹³¹I at 5 yr of age. We diagnosed GHD at age 8 yr 8 months because of growth deceleration (from 95 to 25%) and abnormal growth rate (3 cm/yr) despite euthyroidism, fair glycemic control, and normal weight gain. Both insulin‐like growth factor (IGF) 1 (90 ng/mL; normal 113–261 ng/mL) and IGFBP3 (1.3 mcg/mL; normal 2.1–4.2 mcg/mL) levels were low and peak growth hormone level measured by RIA was 5.2 ng/mL after L‐Dopa and insulin tolerance test. The rest of his pituitary functions and magnetic resonance imaging of the pituitary gland were normal. Growth hormone treatment (0.3 mg/kg/wk) was administered at 8 yr 9 months until near final adult height (FAH). Near FAH (172 cm) was close to midparental target height of 180 cm. GHD may be a component of all APS even though it is rare. Growth in treated children with Graves' disease should be followed closely as catch down growth below genetic height potential may be a harbinger of underlying GHD.     

MMP‐13 expression in keratocyst odontogenic tumour associated with NBCCS and sporadic keratocysts

Oral Diseases (2010) 16 , 795–800 Objective: To investigate the matrix metalloproteinase (MMP)‐13 expression in associated and non‐nevoid basal cell carcinoma syndrome (NBCCS) Odontogenic Keratocysts (OCKs) in order to contribute to a better understanding of the differences in the growth pattern between them. Materials and methods: Thirty‐nine paraffin‐embedded blocks of OCKs, 26 sporadic OCKs and 11 NBCCS‐associated KCOTs were studied by immunohistochemistry to evaluate MMP‐13 expression both in epithelial and stromal layers. A semi‐quantitative scale was used to evaluate immunostaining. Obtained data were compared between the two groups, using Fischer’s exact test and the chi‐square test. Results: Only 13 of 26 sporadic OCKs showed a positive immunostaining, whilst 11 KCOTs resulted in positive labelling for MMP‐13 expression. Moreover, syndromic cysts displayed a more intense and diffuse MMP‐13 labelling of the stromal tissue. Instead, in non‐syndromic forms, the staining pattern of MMP‐13 in stromal tissue was completely absent. Fisher's exact test showed a statistically significant greater prevalence of KCOTs‐immunolabelled cysts with respect to sporadic OCKs. Conclusions: Results from this study point out that the biological behaviour of these cysts could be related not only to the epithelial layer but also to stromal tissue in that... MMP‐13 overexpression in stromal tissue of NBCCS‐associated KCOTs could clarify the higher aggressiveness of these cysts.     

The multifaceted roles of nitric oxide in cancer

The roles of nitric oxide (NO) in numerous disease states have generated considerable discussion over the past several years. NO has been labeled as the causative agent in different pathophysiological mechanisms, yet appears to protect against various chemical species such as those generated under oxidative stress. Similarly, NO appears to exert a dichotomy of effects within the multistage model of cancer. Chronic inflammation can lead to the production of chemical intermediates, among them NO, which in turn can mediate damage to DNA. Yet, NO also appears to be critical for the tumoricidal activity of the immune system. Furthermore, NO can also have a multitude of effects on other aspects of tumor biology, including angiogenesis and metastasis. This report will discuss how the chemistry of NO may impact the initiation and progression stages of cancer.      

A computerized method for rapid quantification of gallbladder volume from real-time sonograms

A computerized method that requires only 1-2 minutes to quantify gallbladder volume from real-time sonograms is described. This time is considerably shorter than that required using the hand-calculation method. There was a highly significant correlation between gallbladder volumes calculated by computer and hand (r = 0.97; P less than .001).