Interaction of high molecular weight kininogen, factor XII, and fibrinogen in plasma at interfaces

Using ellipsometry, anodized tantalum interference color, and Coomassie blue staining in conjunction with immunologic identification of proteins adsorbed at interfaces, we have previously found that fibrinogen is the main constituent deposited by plasma onto many man- made surfaces. However, the fibrinogen deposited from normal plasma onto glass and similar wettable materials is rapidly modified during contact activation until it can no longer be identified antigenically. In earlier publications, we have called this modification of the fibrinogen layer "conversion," to indicate a process of unknown nature. Conversion of adsorbed fibrinogen by the plasma was not accompanied by marked change in film thickness, so that we presumed that this fibrinogen was not covered but replaced by other protein. Conversion is now showen to be markedly delayed in plasma lacking high molecular weight kininogen, slightly delayed in plasma lacking factor XII, and normal in plasma that lack factor XI or prekallikrein. We conclude that intact plasma will quickly replace the fibrinogen it has deposited on glass-like surfaces by high molecular weight kininogen and, to a smaller extent, by factor XII. Platelets adhere preferentially to fibrinogen-coated surfaces; human platelets adhere to hydrophobic nonactivating surfaces, since on these, adsorbed firbinogen is not exchanged by the plasma. The adsorbed fibrinogen will be replaced on glass-like surfaces during surface activation of clotting, and platelets failing to find fibrinogen will not adhere.     

Efficacy of transarterial chemoembolization prior to liver transplantation for hepatocellular carcinoma as found in pathology

BACKGROUND/AIMS: To analyze the efficacy of chemoembolization prior to liver transplantation in liver explants. METHODOLOGY: We reviewed pathological findings in the explanted livers of 21 patients with histologically proven hepatocellular carcinoma and liver cirrhosis who underwent transarterial chemoembolization (TACE) prior to liver transplantation. Nine patients had solitary nodules with a median diameter of 4 cm (range 1.5-7 cm), 7 patients had 2 or 3 tumors with a median total diameter of 5.9 cm (range 3-9 cm) and 5 patients had a multifocal tumor prior to TACE. Pathological up-staging of the clinical tumor classification was documented as "tumor-progression." Concurrence of clinical and pathological findings was documented as "steady disease". "Tumor regression" described those cases in which the pathological classification downgraded the clinical findings. RESULTS: There was no treatment-related morbidity in these patients' group. Tumor regression was proved in 11/21 patients (52.4%) whereas steady disease was observed in 7/21 patients (33.4%). In 5 patients (23.8%) no vital tumor was found by pathological examination. Tumor regression was observed only in one of the five patients having a multifocal tumor prior to TACE. Tumor progression was observed in 3/21 patients (14.3%). CONCLUSIONS: Our data show that TACE provides acceptable local tumor control as bridging treatment before liver transplantation. Although the majority of our patients (15/21, 71.4%) had 2 or more tumor lesions at the beginning of treatment, tumor progression was observed in only a minority (14.3%) of patients. However, multifocal tumors could not be successfully under-staged through this treatment and, furthermore, vital tumor was always observed in pathology; the usefulness of TACE in multifocal disease has to be re-estimated.     

Absence of alternative splicing in bcr-abl mRNA in chronic myeloid leukemia cell lines

The major consequence of the Philadelphia (Ph) translocation in chronic myeloid leukemia (CML) is the formation of a bcr-abl hybrid oncogene encoding a tumor cell-specific protein P210bcr-abl. In contrast to this, in Ph chromosome-positive acute lymphoblastic leukemia (Ph + ALL), a P190bcr-abl can be observed. This P190bcr-abl has been implicated in acute rather than chronic leukemogenesis. Therefore, it can be hypothesized that the transition from chronic to blast phase in CML is accompanied by an alternative splice in the bcr-abl mRNA, which results in a switch of the production of P210bcr-abl into P190bcr-abl. Initial S1 nuclease protection mapping supported this theory. However, this result appears to be based on an artifact in the S1 analysis. By using the polymerase chain reaction we provide evidence for the absence of alternative splicing in bcr-abl mRNA in two CML blast crisis cell lines.     

Effect of active site-modified thrombin on the hydrolysis of platelet- associated glycoprotein V by native thrombin

To determine the relationship between equilibrium binding of thrombin to sites on the platelet surface and the cleavage of membrane glycoprotein V (GPV) by thrombin, we examined the effect of active site- modified thrombin (1-chloro-3-tosylamido-7-amino-L-2-heptanone thrombin toslysCH2-thrombin) on the binding of native thrombin to platelets and on the hydrolysis of GPV by native thrombin. ToslysCH2-thrombin inhibited binding of native thrombin to high affinity sites on the platelet surface. In contrast, hydrolysis of GPV by native thrombin, even at threshold thrombin concentrations, was not inhibited by pretreatment with toslysCH2-thrombin at concentrations up to 210 nmol/L. ToslysCH2-thrombin also had no appreciable effect on platelet aggregation or release of 14C-serotonin induced by native thrombin. Because toslysCH2-thrombin does not inhibit platelet release, aggregation, or GPV hydrolysis by native thrombin but does inhibit high affinity surface binding by native thrombin, these results indicate that thrombin binding and hydrolysis of GPV are separate and unrelated events.     

猪脑钠素及其类似物的合成

以固相多肽合成方法合成了猪的二十六肽脑钠素(BNP)和它的一个类似物(Mpr⁴,D-Ala^6,13)-BNP(4-24)-NH₂,保护肽用HF裂解除去保护基、在碱性条件下空气氧化形成二硫桥后,粗产物经凝胶过滤和高效液相色谱分离纯化,均有与天然脑钠素相同的活性。合成肽相对于树脂初始取代量的产率分别为9.56%和11.03%。     

交沙霉素在中国汉族、维吾尔族及哈萨克族中的药代动力学比较

交沙霉素在中国汉族、维吾尔族及哈萨克族中的药代动力学比较李国昌陈春雁杨明义（新疆石河子医学院第一附属医院药剂科，石河子８３２００８；石河子农学院医院，石河子８３２００３）为探讨交沙霉素（ｊｏｓａｍｙｃｉｎ）在不同民族正常人体内过程，我们用相同的受...     

Women worried about their familial breast cancer risk--a study on genetic advice in general practice

AIMS: To ascertain whether women who consulted their GP because they perceived themselves as at increased risk of familial breast cancer were indeed at increased risk, and to evaluate potential strategies for assessing genetic risk of breast cancer in general practice. METHODS: Sixty-seven out of 81 women who had consulted their GP for advice about their possible increased risk of developing breast cancer due to breast cancer in the family were interviewed. Familial breast cancer risk was assessed by a clinical geneticist. This assessment was compared with two recent guidelines for referral for genetic counselling. RESULTS: More than half (52%; n = 35) the women had a relative risk of two and over for developing breast cancer, while another half of these 35 (25%; n = 17) had a relative risk of three and over. All the women (n = 17) with a relative risk of three and over were identified by means of the two current guidelines for referral for genetic counselling, while more than half of the women (61%; n = 11) with a relative risk between two and three were identified. CONCLUSIONS: More than half the women concerned about their familial risk of breast cancer are indeed at increased risk of breast cancer. Current guidelines correctly identify women at high risk. However, doubts about the health gain and feasibility of referral warrant caution, and need further investigation.