New variant of von Willebrand disease with defective binding to factor VIII

A new variant of von Willebrand disease (vWD) was identified by a new analytic method which characterizes the ability of plasma von Willebrand Factor (vWF) to bind to purified factor VIII (F.VIII). vWF was isolated from small amounts of plasma by immunoadsorption with a selected monoclonal antibody to vWF previously coated onto wells of microtitration plates. Plasma F.VIII was removed from immobilized vWF by washing with 0.4 mol/L CaCl2; purified F.VIII was then added to the well. The amount of bound F.VIII was estimated directly in the wells by a chromogenic assay and immobilized vWF was estimated by an immunologic a pool of normal plasma, ten control individuals, 13 with hemophilia A and five with type I vWD. In all cases, the dose-response curves were linear and the slopes of the regression lines were essentially the same. The method was then applied to investigate the binding of vWF to F.VIII in two vWD patients (sister and brother) who demonstrated significantly lower activity of F.VIII than of vWF. The first patient, with a long history of epistaxis, bruising, and hematomas, showed a slightly prolonged bleeding time (10 minutes); 15% VIII:C and 39% of vWF:Ag and vWFRCo. Her brother, who has a bleeding syndrome but no hematomas, showed similar data (bleeding time 9 minutes, 20% VIII:C, 53% vWF:Ag and vWFRCo). Similar levels of F.VIII were observed in the two propositi by four different methods (one- and two-stage clotting and chromogenic and immunologic assays). Sodium dodecyl sulfate (SDS) 1.4% agarose gel electrophoresis showed that all multimers of vWF were present in both patients. vWF binding to F.VIII was markedly decreased in the two propositi. The abnormal binding of vWF to F.VIII was not corrected during pregnancy or after infusion of 1-deamino (8-D- arginine) vasopressin despite an increase in vWF levels. The qualitative abnormality of vWF in both patients was associated with a subtle alteration of the multimeric structure by SDS 3% agarose gel electrophoresis in which the two central subbands of the quintuplet of individual oligomers were undetectable or poorly visible. SDS- polyacrylamide gel electrophoresis under reducing conditions demonstrated a single band of 275 Kd in the plasma of both patients, and there was no evidence of a second band corresponding to pro-vWF, the precursor of the mature vWF subunit, suggesting that proteolytic processing of vWF was normal.(ABSTRACT TRUNCATED AT 400 WORDS)     

Determination of the N-terminal sequence of human red cell Rh(D) polypeptide and demonstration that the Rh(D), (c), and (E) antigens are carried by distinct polypeptide chains

Human monoclonal antibodies (MoAbs) directed against the blood group Rh(D), (c), and (E) antigens produced by Epstein-Barr virus (EBV)- transformed lymphoblastoid cell lines have been used to characterize the Rh components of human red cell membranes and to determine whether the Rh(D), (c), and (E) epitopes are carried by distinct polypeptides. After immunoprecipitation with the anti-Rh(D) antibody and preparative gel electrophoresis, a homogenous preparation of the Rh(D) protein was obtained from two different erythrocyte samples (Blo and D--/D--), which have an increased density of Rh(D) antigen. Both preparations exhibited the same N-terminal sequence (S)-(S)-K-Y-P-R-S-V-R-R-(L)-L-P- L-X-A, indicating that different Rh(D)-positive red cells are carrying a similar Rh(D) protein. Comparative immunoprecipitation studies with the human monoclonal anti-Rh(D), (c), and (E) antibodies have also shown that Rh components from intact and papain-treated erythrocytes have similar apparent mol wt of 30 to 32 Kd and are buried in the lipid bilayer and are not readily available to the proteolytic enzyme. Further investigations by indirect affinity chromatography and one- dimensional peptide mapping of the Rh(D), (c), and (E) molecules immunopurified from a single red cell sample demonstrate that a common Rh haplotype encodes three distinct polypeptide chains carrying the Rh(D), (c), and (E) epitopes, respectively.     

Direct demonstration of an HLA-DR allotypic determinant on the low molecular weight (beta) subunit using a mouse monoclonal antibody specific for DR3

A murine monoclonal antibody directed against a human B cell surface antigen with the characteristics of HLA-DR is described. The antigen detected is tightly linked to HLA and is correlated with the alloantigen HLA-Dw/DR3. Reactivity with a fraction of Dw/DRw6 cells is also observed. The determinant recognized by this antibody has been shown to be present on the smaller molecular weight β subunit of the HLA-DR antigen.     

人工听骨链重建材料的生物相容性及其应用特点

目的:随着耳显微外科的迅速发展及鼓室成形术的推广,对听骨链重建材料的研究也逐步深入。分析几种听骨链重建材料的材料学特性及其在应用过程中存在的优缺点。方法:应用计算机检索中国期刊全文数据库1998-01/2007-06有关听骨链重建材料方面的相关文献,检索词"人工听骨、听骨链重建、生物相容性",限定文献语言种类为中文。共检索到文献102篇,对资料进行初审,并查找全文。纳入标准:①不同材料在听骨链重建中应用的相关文献。②听骨链重建材料的选择、设计及生物学特性评价的相关文献。排除标准:重复研究。最终纳入21篇符合标准的文献。结果:①自体移植材料具有较好的声导性和生物相容性,在体内无排斥反应。但自体听骨由于常残留微小病灶,易造成术后感染;自体软骨柔软易变形,术后易发生粘连;自体皮质骨取材不易,取材后加工塑形困难。②同种异体材料生物相容性好,可于术前雕刻成不同的形状,但贮存条件要求较高,有传播疾病的可能。③多孔高分子聚乙烯的显著优点是质轻且多孔,适合组织长入,但具有不稳定性、易脱位的缺点。④羟基磷灰石陶瓷人工听骨生物相容性极佳,单纯羟基磷灰石人工听骨不具备骨诱导能力,与骨形态发生蛋白结合后,可使复合材料拥有骨传导和诱导的双重特性。⑤钛质人工听骨生物相容性和组织亲合性佳、耐久性好、重量轻、可塑性强、不易脱位,是一种有推广前景的听骨修复材料。结论:不同听骨链重建材料均存在各自的优缺点,还有待进一步完善,应用结合各种材料优点的复合听骨链重建材料将成为趋势。     

Orexin/hypocretin receptor signalling cascades

Orexin (hypocretin) peptides and their two known G-protein-coupled receptors play essential roles in sleep–wake control and powerfully influence other systems regulating appetite/metabolism, stress and reward. Consequently, drugs that influence signalling by these receptors may provide novel therapeutic opportunities for treating sleep disorders, obesity and addiction. It is therefore critical to understand how these receptors operate, the nature of the signalling cascades they engage and their physiological targets. In this review, we evaluate what is currently known about orexin receptor signalling cascades, while a sister review (Leonard & Kukkonen, this issue) focuses on tissue-specific responses. The evidence suggests that orexin receptor signalling is multifaceted and is substantially more diverse than originally thought. Indeed, orexin receptors are able to couple to members of at least three G-protein families and possibly other proteins, through which they regulate non-selective cation channels, phospholipases, adenylyl cyclase, and protein and lipid kinases. In the central nervous system, orexin receptors produce neuroexcitation by postsynaptic depolarization via activation of non-selective cation channels, inhibition of K⁺ channels and activation of Na⁺/Ca²⁺ exchange, but they also can stimulate the release of neurotransmitters by presynaptic actions and modulate synaptic plasticity. Ca²⁺ signalling is also prominently influenced by these receptors, both via the classical phospholipase C−Ca²⁺ release pathway and via Ca²⁺ influx, mediated by several pathways. Upon longer-lasting stimulation, plastic effects are observed in some cell types, while others, especially cancer cells, are stimulated to die. Thus, orexin receptor signals appear highly tunable, depending on the milieu in which they are operating.Linked ArticlesThis article is part of a themed section on Orexin Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-2     

Post‐implantation events of swan‐neck catheters for PD

The first step in PD is the implantation of a peritoneal catheter, a technique that is subject to different possible incidences. We have studied the non‐infectious events or incidences (pericatheter leakage, blood tinged dialysate, catheter displacement, omental wrapping and extra‐peritoneal placement) registered in our unit during a five‐year period (1992–1996) after the implantation of 144 swan‐neck curled catheters in 100 peritoneal dialysis patients, 49 males and 51 females. 70 catheters (48.61 %) were implanted using the blind puncture method and 74 (51.39 %) with the surgical method. All the incidence rates were compared between the two methods to analyse the possible influence of the implantation technique. 21 pericatheter leaks, 19 episodes of blood tinged dialysate, 10 displacements, 7 cases of omental wrapping and 4 extra‐peritoneal placements (all of them after blind punctures carried out by young assistant doctors) were registered, with a total number of 61 incidences (0.42 per catheter). Statistically significant differences were not found either globally or for each type of event when comparing the incidence rates between the two implantation techniques, although extra‐peritoneal placement was close to significant (p = 0.053). None of the incidences were severe. 25 catheters (17.4%) had to be replaced with the removal rates being similar for both techniques. In conclusion, in our experience neither technique shows a clear advantage over the other. Experienced staff members should implant PD catheters.     

Development and validation of nail psoriasis quality of life scale (NPQ10)

Background The chronic and treatment‐resistant nature of nail psoriasis affects patients’ lives not only physically but also psychologically. Although there are scoring systems available for disease severity, there is as yet no scale to evaluate the impact of this condition upon the patients’ quality of life. Objectives This study aims to develop and validate a quality of life scale specifically for nail psoriasis. Methods A questionnaire was developed during a study conducted in France between 2004 and 2005. With the cooperation of l’Association Pour la Lutte Contre le Psoriasis, the questionnaire was sent to a random sample of 4000 of its 17 000 members. Results The response rate was 33%. Of the 1309 questionnaires returned, 795 showed the presence of nail psoriasis and these were eligible. The scale score is obtained by adding together the responses to the 10 questionnaire items and the result is expressed as a percentage. The value of the score obtained is proportional to the functional difficulty experienced. The determination of Cronbach's α coefficient and a Principal Component Factor Analysis show, respectively, very good internal consistency and the unidimensional nature of the scale. Test–retest results on 15 patients showed good reproducibility. Results were validated with reference to the Dermatology Life Quality Index. In this study, the NPQ10 score is significantly influenced by gender (women have a higher score) and by the duration of psoriasis (recent onset implies greater functional difficulty). Finally, the score is much higher when the nail psoriasis affects both the hands and the feet. Conclusion This study confirms a change in the quality of life of patients who have nail psoriasis. The NPQ10 scale, specific to this condition, is simple to use and has the attributes needed in a quality of life scale. The scale must now be tested in longitudinal studies (such as clinical trials) to confirm its ability to measure a change in status.     

No association between nickel allergy and reporting cosmetic dermatitis from mascara or eye shadow: a cross‐sectional general population study

Background In theory, all pigmented make‐up products may contain metal allergens including nickel. Eyelid dermatitis has previously been observed among nickel allergic dermatitis patients following exposure to nickel containing mascara and eye shadow. However, an association between nickel eyelid dermatitis and nickel in make‐up products remains controversial. Objective This cross‐sectional patch test study investigated whether the frequency of self‐reported cosmetic dermatitis from mascara or eye shadow use was higher among nickel allergic Danish women than women without nickel allergy. Methods In 2006, a total of 1843 18–69 year old women completed a postal questionnaire including questions on cosmetic dermatitis and were patch tested with nickel sulphate. Data were analysed by logistic regression analyses and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Results The prevalence of nickel allergy was similar among women who reported cosmetic dermatitis from eye shadow or mascara and among women who did not report such symptoms. Cosmetic dermatitis was positively associated with self‐reported atopic dermatitis and age. Conclusion Overall, no association between having nickel allergy and reporting cosmetic dermatitis from mascara or eye shadow use was found in the general population. This does not exclude a causal relationship in selected cases.