The C-terminal sequences of the gamma 57.5 chain of human fibrinogen constitute a plasmin sensitive epitope that is exposed in crosslinked fibrin

The gamma chain of human plasma fibrinogen is heterogeneous with three forms differing in length at the C-terminus. Alternative RNA splicing produces two gamma chain mRNAs encoding gamma 50 and gamma 57.5 polypeptides, while fibrinogen gamma 55 is produced by post- translational modification of the gamma 57.5 chain. The composition of purified variant gamma chain fibrinogens, which comprise 10% to 13% total plasma fibrinogen, is predominantly heterodimeric (A alpha, B beta, gamma 50/gamma 55 or A alpha, B beta, gamma 50/gamma 57.5), whereas the composition of purified fibrinogen with the major form of the gamma chain is homodimeric (A alpha, B beta, gamma 50/gamma 50). These gamma chain variations interrupt sequences that mediate platelet- fibrinogen interactions. Therefore, the structure and function of gamma 57.5 C-terminal sequences were investigated using synthetic peptides and a specific monoclonal antibody (MoAb), L2B. The L2B epitope was localized and included gamma 57.5 chain residues 409-412 (Arg-Pro-Glu- His), as determined by differential enzyme-linked immunosorbent assay (ELISA) reactivity with a His-412 deleted synthetic peptide and by Western blot analysis of plasmin cleaved fibrinogen gamma 57.5. L2B had no effect on adenosine diphosphate (ADP)-induced platelet aggregation supported by either fibrinogen gamma 50 or gamma 57.5. High concentrations (0.5 to 1 mmol/L) of synthetic peptide gamma 57.5 405- 416 only weakly inhibited ADP-induced platelet aggregation supported by either fibrinogen gamma 50 or gamma 57.5. Binding of fibrinogen gamma 50 (IC50 = 780 mumol/L) or gamma 57.5 (IC50 = 650 mumol/L) to ADP- stimulated platelets was weakly inhibited, and MoAb L2B failed to inhibit fibrinogen gamma 57.5 binding. Peptide gamma 57.5 408-416 failed to dissociate platelet-bound fibrinogens. These data indicate that the gamma 408-416 sequence of fibrinogen gamma 55 or gamma 57.5 alone is unlikely to bind to the platelet fibrinogen receptor, glycoprotein llb-llla (GPllb-llla), in support of platelet aggregation under physiologic conditions. The sequence recognized by L2B does not resemble known GPllb-llla binding site peptide sequences [Arg-Gly-Asp- Ser (RGDS) or gamma 50 400-411] as determined by competitive inhibition ELISA comparing these binding site synthetic peptides with gamma 57.5 408-416. This epitope is available for binding MoAb L2B in gamma 55 or gamma 57.5 chain dimers and binds to all gamma 57.5 408-416 epitopes equally in non-crosslinked and factor Xllla crosslinked fibrin clots.(ABSTRACT TRUNCATED AT 400 WORDS)     

Twenty four hour variation in plasma atrial natriuretic factor during VVI and DDD pacing.

OBJECTIVE: To investigate whether plasma atrial natriuretic factor (ANF) follows a pattern of circadian variation similar to that of other hormones in patients paced under VVI and DDD pacing modes and to determine if the known effect of pacing mode on ANF secretion is maintained throughout the 24 hour period. PATIENTS AND DESIGN: 20 patients were studied. They had complete atrioventricular block and had been paced for 17 (SD 3.5) months with a dual chamber multiprogrammable pacemaker. They were divided into two groups according to the duration of pacing in either VVI or DDD mode before the measurements: group A, n = 11 (8 men, 3 women, aged 65 (7) years), each paced for 24 h under each of VVI and DDD modes in random order; group B, n = 9 (7 men, 2 women, aged 63 (8) years), each paced for 60 d under each pacing mode before the measurements. Blood samples were taken and ANF concentrations measured every 4 h over a 24 h period, starting at 09.00. Measurements were also made of plasma cortisol, which has a known circadian pattern, so that the 24 h curve could be compared with that of ANF. RESULTS: In contrast to cortisol, ANF values indicated a pulsatile pattern of secretion throughout the 24 h period, with no clear circadian variation. In group B, ANF concentrations were significantly higher during VVI than during DDD pacing throughout the 24 h period, whereas in group A this difference was statistically significant only at certain times of day. CONCLUSIONS: ANF does not show the circadian pattern of variation shown by cortisol and other hormones. Dual chamber pacing contributes to an improvement not only in cardiac haemodynamics but also in the neuroendocrine system, especially in the long term.     

Linkage of polymorphic congenital cataract to the gamma-crystallin gene locus on human chromosome 2q33-35

Cataract is one of the major causes of blindness in humans. We describe here an autosomal dominant polymorphic congenital cataract (PCC) which is characterised by wide variations in phenotype of non-nuclear lens opacities, even among affected members of the same family. PCC families included a large, unique pedigree (254 members, 103 affected individuals), and genetic linkage was conducted using a variety of polymorphic markers. Evidence for linkage was found for chromosome 2q33- 35 with PCC mapping near D2S72 and TNP1. A tri-nucleotide microsatellite marker for gamma-crystallin B gene (CRYG1) was found to co-segregate with PCC and yielded a maximum lod score of 10.62 at (theta = 0). A multipoint analysis demonstrated that the most probable location of the PCC gene was within an 8 cM genetic interval containing the gamma-crystallin gene cluster. These data provide strong evidence of the existence of an autosomal dominant mutation for PCC in or near the gamma-crystallin gene cluster. This defect is characterised by complete penetrance but variable expression of the cataract phenotype. Our study also suggests that non-nuclear human cataracts might be caused by some abnormality in gamma-crystallin genes.      

Gestational trophoblastic neoplasia: diagnosis with Doppler US

The sonographic appearance of gestational trophoblastic neoplasia is nonspecific and also seen in complete or partial hydatidiform mole, hydropic degeneration, degenerating fibroids, or ovarian dysgerminomas. Correlation with the serum human chorionic gonadotropin (hCG) level may be helpful since levels exceeding 100,000 IU/L are strongly suggestive of gestational trophoblastic neoplasia. However, low hCG levels may also be found in the presence of this disease. The authors studied six patients who were suspected of having gestational trophoblastic neoplasia. Three of the six proved to have incomplete abortions or molar degeneration. Doppler ultrasound (US) was used to record the signal in the uterine arteries of these patients. The signals were compared with those of three nongravid volunteers and three patients in the first trimester of pregnancy. Analysis of the signals in the uterine artery showed higher systolic and diastolic Doppler shifts in gestational trophoblastic neoplasia when compared with postabortal, gravid, and nongravid signals. These preliminary results indicate that Doppler US has the potential to be clinically useful in the diagnosis of gestational trophoblastic neoplasia.     

健康信念模式在早期宫颈癌患者健康教育中应用观察

目的探讨健康信念模式在早期宫颈癌患者健康教育中应用价值。方法选取该院2013年1月—2014年6月收治的90例早期宫颈癌患者,随机分为两组,对照组和观察组各45例,对照组患者应用标准健康计划指导,观察组患者实施健康信念模式,比较两组患者采用不同的健康教育方式后患者对宫颈癌基本知识、自我保健知识的掌握情况。结果观察组患者对疾病知晓和掌握程度明显优于对照组,观察组掌握率高达93.3%（42/45）,与对照组的75.6%（34/45）差异有统计学意义（P〈0.05）;观察组自我保健知识掌握率为95.6%（43/45）,对照组掌握率为82.2%（37/45）,差异有统计学意义（P〈0.05）;观察组对护理工作满意度显著高于对照组（P〈0.05）。结论对早期宫颈癌患者健康教育中采用健康信念模式具有明显的临床价值,有助于提升患者对疾病的认识,增强健康信念,养成良好的生活习惯,积极主动的做好预防措施,有效降低并发症发生率,值得在临床上进一步推广。     

THE PHYSICIAN IN COURT: A VIEW FROM THE BENCH

Only lawyers and judges-and not even all of them-look forward to being in court. For the physician it is usually not an experience sought or savoured. Yet some physicians are in court more frequently than some lawyers because they are expert witnesses or because they have treated a person who is before the court in a civil or criminal case. There is also the physician who is sued and is thus a defendant. I believe it important that physicians know the basic ingredients of a civil action. I will be drawing on my experience as a trial judge for eight years and an Alberta Court of Appeal judge for five, and as a former professor in the faculties of law and medicine at the University of Alberta, to present the perspective from the bench on civil non-jury actions.     

氨溴特罗口服液治疗支气管炎患儿的效果

目的：观察氨溴特罗口服液治疗支气管炎患儿的效果。方法选取承德市中医院2013年7月~2014年7月收治的支气管炎患儿100例,将其随机分为A、B两组。两组患儿均在常规治疗基础上分别给予氨溴特罗口服液及盐酸氨溴索糖浆进行治疗。比较两组患儿不同药物治疗后症状控制情况及治疗总有效率等指标。结果 A组患儿咳嗽、咳痰、喘息、肺部啰音、憋闷缓解时间及住院时间分别为(7.4±1.2)、(6.1±1.1)、(6.0±1.2)、(4.7±1.5)、(3.7±1.1)、(9.1±1.4)d,均显著短于B组[(10.3±2.1)、(8.4±1.2)、(7.5±1.4)、(5.2±1.3)、(4.3±1.4)、(13.7±1.5)d],差异有统计学意义(P约0.05)。A组患儿治疗后显效29例(58.0%),有效21例(42.0%),总有效率(100.0%)显著优于B组患儿[显效17例(34.0%),有效20例(40.0%),总有效率(74.0%)],两组总有效率比较,差异有统计学意义(P约0.05)。治疗后A组患儿咳嗽症状、咳痰量、痰液黏稠程度评分均较治疗前及B组患儿明显改善,差异有统计学意义(P约0.05)。结论临床应用氨溴特罗口服液可在短时间内缓解患儿咳嗽、发热等不适症状并缓解支气管痉挛。服药后起效速度快,且药效发挥时间长,有助于痰液排出并有效抑制炎性物质释放。服药后患儿不良反应较少,治疗安全性高,对加快疾病治疗速度、改善患儿预后情况并提高其生活质量具有重要意义。