Comparative study on electrocardiograms and serological examinations of acute pulmonary embolism and acute non‐ST elevation myocardial infarction

BackgroundThe aim of this study was to investigate the value of electrocardiograms (ECGs) and serological examinations in the differential diagnosis of acute pulmonary embolism (APE) and acute non‐ST elevation myocardial infarction (NSTEMI) in order to reduce the rate of clinical misdiagnosis.MethodsThe clinical data of 37 patients with APE and 103 patients with NSTEMI admitted to our hospital were retrospectively analyzed. The differences in the clinical manifestations, ECGs, myocardial zymograms, D‐dimers, and troponin (cTn) of the two groups were compared.ResultsIn the patients with APE, the main symptom—found in 25 cases (67.56%)—was dyspnea, while in the patients with NSTEMI, the main symptom—found in 52 cases (50.49%)—was chest tightness. The incidences of sinus tachycardia and S_IQ_IIIT_III in the group of patients with APE were higher than in the group of patients with NSTEMI, and the difference was statistically significant (p < .05). There was no statistical significance in the difference of aspartate aminotransferase and lactate dehydrogenase (LDH) in the two groups (p > .05), although there was a statistically significant difference of creatine kinase (CK) and the creatine kinase isoenzyme‐MB (CK‐MB) in the two groups (p < .05). The levels of D‐dimers and cTn were increased in both groups, but the level of D‐dimers in the group of patients with APE was higher than that in the group of patients with NSTEMI.ConclusionWith the occurrence of clinical manifestations like dyspnea, chest tightness, chest pain, and palpitation of unknown causes, the possibility of APE and NSTEMI should be considered.     

Three residues at the interface of factor XI (FXI) monomers augment covalent dimerization of FXI

Summary.  Background:  Human plasma factor XI is a homodimer, with each monomer comprising a catalytic domain and four homologous 'apple' domains. The monomers bind to each other through non-covalent bonds and through a disulfide bond between Cys321 residues in apple 4 domains. Objective:  To identify residues essential for dimerization in the FXI monomer interface. Methods:  Specificity-determining residues in apple 4 domains were sought by sequence alignment of FXI and prekallikrein apple domains in different species. Specific residues identified in apple 4 domains were mutagenized and expressed in baby hamster kidney (BHK) cells for evaluation of their effect on FXI dimerization, analyzed by non-reduced sodium dodecylsulfate polyacrylamide gel electrophoresis and size-exclusion chromatography. Results:  Among the 19 residues of the FXI monomer interface, Leu284, Ile290 and Tyr329 were defined as specificity-determining residues. Substitutions of these residues or pairs of residues did not affect FXI synthesis and secretion from transfected BHK cells, but did impair dimerization, despite the presence of cysteine at position 321. The double mutant 284A/290A yielded predominantly a monomer, whereas all other single or double mutants yielded monomers as well as disulfide-bonded dimers. Conclusions:  The data suggest that Leu284, Ile290 and Tyr329 in the interface of FXI monomers are essential for forming non-covalently bonded dimers that facilitate formation of a disulfide-bonded stable FXI dimer.     

疏血通注射液对急性脑梗塞患者治疗前后血浆D-D和血清HCY、IL-6浓度的影响

目的:探讨疏血通注射液对急性脑梗塞患者治疗前后血浆D-D和血清HCY、IL-6浓度的影响。方法:应用化学发光法和酶联法对36例急性脑梗塞患者进行血浆D-D和血清HCY、IL-6水平检测,并与35名正常健康人作比较。结果:急性脑梗塞患者在治疗前血浆D-D和血清HCY、IL-6水平均非常显著高于正常人组(P0.01),经疏血通注射液治疗2周后则与正常人比较无显著性差异(P0.05),血浆D-D水平与HCY、IL-6水平呈显著正相关(r=0.5238、0.6018、P0.01)。结论:检测急性脑梗塞患者治疗前后血浆D-D和血清HCY、IL-6水平的变化,对了解病情、观察疗效和预后判定均具有一定的临床价值。     

Structural and functional features of factor XI

Summary.  Factor XI (FXI) has structural and mechanistic features that distinguish it from other coagulation proteases. A relatively recent addition to vertebrate plasma coagulation, FXI is a homodimer, with each subunit containing four apple domains and a protease domain. The apple domains form a disk structure with binding sites for platelets, high molecular weight kininogen, and the substrate factor IX (FIX). FXI is converted to the active protease FXIa by cleavage of the Arg³⁶⁹−Ile³⁷⁰ bond on each subunit. This converts the catalytic domains to the active forms, and unmasks exosites on the apple domains required for FIX binding. FXI activation by factor XIIa or thrombin proceeds through an intermediate with only one activated submit (1/2-FXIa). 1/2-FXIa activates FIX in a similar manner to FXIa. While the importance of the homodimeric structure of FXI is not certain, it may represent a strategy for binding to FIX and a platelet surface simultaneously.     

血浆D-二聚体水平变化在心脏房颤血栓前状态诊断的意义

目的探讨房颤持续时间与复律前后血浆D-二聚体水平的变化关系。方法将42例心脏房颤病人分成A、B两组,A组房颤持续时间为72h或以上(142.7±103.8h),B组房颤持续时间少于72h(25±16h)。以酶免疫法测定对复律前和复律后36h的血浆D-二聚体水平,并与19例对照组比较。结果与对照组相比,A、B两组病例复律前血浆D-二聚体水平均明显增高(P<0.05),并与房颤持续时间有显著相关。结论房颤持续时间越长,复律后血栓前状态越明显;房颤持续时间和D-二聚体水平可作为房颤复律血栓前状态的新的预测物。     

Diagnosis of deep vein thrombosis by plasma-soluble fibrin or D-dimer

The present study was designed to determine the cutoff values of D-dimer and soluble fibrin (SF) for the diagnosis of deep venous thrombosis (DVT) and pulmonary embolism (PE) in Japanese patients. Plasma levels of these molecules were measured in 243 patients suspected of having DVT and 100 healthy volunteers (controls). Out of 243 patients, 20 patients were diagnosed with DVT. In the control group, plasma levels of D-dimer and SF did not show normal distribution, and the 95% confidence intervals (CI) of D-dimer and SF were 2.45 microg/mL and 6.92 microg/mL, respectively. Plasma levels of D-dimer and SF of patients with DVT were significantly higher than of those without DVT. In patients with DVT, the minimum values of D-dimer and SF were 1.71 and 1.44 microg/mL, respectively. When the cutoff value was set at the average+1 SD of those of the control (D-dimer, about 1.8 microg/mL; SF, about 1.4 microg/mL), 1 and 0 patient with DVT was overlooked, respectively. The sensitivity and specificity of D-dimer and SF for DVT were 95% and 100%, and 61.9% and 53.8%, respectively. When the cutoff value was set at 95% CI of the control (D-dimer, 2.5 microg/mL; SF, 6.9 microg/mL), 2 and 9 patients with DVT were overlooked, respectively. The sensitivity and specificity of D-dimer and SF were 90% and 50%, and 77.6% and 88.3%, respectively. When the cutoff values set at 2.5 microg/mL of D-dimer or 6.9 microg/mL of SF, 1 DVT patient was overlooked, with sensitivity and specificity of 95% and 69.5%. Our data suggest that both D-dimer and SF are useful markers for the diagnosis of DVT and that measurement of both D-dimer and SF increases the sensitivity and specificity for the diagnosis of DVT/PE.     

HLA-Ig-based artificial antigen-presenting cells: setting the terms of engagement

Recent advances in molecular medicine have shown that soluble MHC-multimers can be valuable tools for both the stimulation of as well as the analysis of antigen-specific T cells in vitro. In this review, we describe the use of dimeric major histocompatibility complexes, HLA-Ig, to visualize antigen-specific T cells as well as their potential to stimulate immune responses as part of an artificial antigen-presenting cell (aAPC). The use of HLA-Ig-based aAPC represents an exciting new approach to generate antigen-specific CTL for adoptive immunotherapy that helps to overcome many of the obstacles associated with limitations in current approaches to adoptive immunotherapy.     

Part II: influence of dimerization of a modified GnRH-I peptide sequence on a male antifertility vaccine

PROBLEM: In the previous paper, we described how the tetanus toxoid (TT) conjugated monomer, CHWSYGLRPG-NH2, induced high neutralizing antibody titres, which resulted in decreased levels of testosterone and subsequent antifertility. However, its counterpart HWSYGLRPGC, induced low avidity antibody titres. We wanted to know whether peptide dimerization would improve the efficacy of both peptides. METHOD OF STUDY: Male Sprague-Dawley rats were immunized with modified dimerized GnRH-I peptides (HWSYGLRPGCCGPRLGYSWH and GPRLGYSWHCCHWSYGLRPG-NH2), with or without conjugation to TT. RESULTS: The unconjugated dimers were not effective in causing castration, although the first peptide dimer did induce production of antibodies. When conjugated to TT, both dimers showed the same level of efficacy in causing castration as each other. However, there were differences in antibody binding to native GnRH. CONCLUSIONS: Dimerization and conjugation to a carrier improved the antifertility efficacy of HWSYGLRPGC, whereas the conjugated monomer CHWSYGLRPG-NH2 showed a greater level of consistent castration than its conjugated dimer.     

High levels of 8-hydroxy-2'-deoxyguanosine appear in normal human epidermis after a single dose of ultraviolet radiation

Major photoproducts induced by carcinogenic ultraviolet (UV) radiation are the cylobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (6-4 PPs). 8-Hydroxy-2 -deoxyguanosine (8-OHdG) is also a DNA base-modified product generated by reactive oxygen species in conditions of ultraviolet stress, Although UVB-induced CPDs and 6-4 PPs have been investigated in animal and human skin, little is known about the role of 8-OHdG in UVB-induced human skin damage or carcinogenesis. Normal human skin from three volunteers was exposed to UV radiation, and the time course of induction and removal of 8-OHdG was examined by immunohistochemical analysis with catalysed signal amplification on formalin-fixed paraffin sections. Formation of CPDs and 6-4 PPs was also examined by immunostaining on the same skin specimens. Control epidermis with no exposure to UV radiation showed little nuclear staining of 8-OHdG, but an increased level of 8-OHdG was clearly observed in epidermis biopsied after irradiation. Induced 8-OHdG can rapidly be removed from nucleus during the first 24-48 h, as the staining intensity diminished gradually, almost reaching the control level by 72-96 h after irradiation. Staining for CPDs or 6-4 PPs revealed induction of these photoproducts in human skin, although 6-4 PP-positive cells disappeared more rapidly than those that stained for CPDs or 8-OHdG. Together with protective effect of antioxidants, our results indicate that not only CPDs and 6-4 PPs but also 8-OHdG may play a significant part in UV carcinogenesis.     

D‐dimer levels and stroke progression in patients with acute ischemic stroke and atrial fibrillation

Krarup L‐H, Sandset EC, Sandset PM, Berge E. D‐dimer levels and stroke progression in patients with acute ischemic stroke and atrial fibrillation.
Acta Neurol Scand: 2011: 124: 40–44.
© 2010 John Wiley & Sons A/S. Background – Patients with acute ischemic stroke and atrial fibrillation are at increased risk of stroke progression and recurrence. We sought to assess whether D‐dimer and other markers of hemostatic activation could predict these adverse events in such patients. Method – Blood samples were obtained from patients included in the Heparin in Acute Embolic Stroke Trial. Stroke progression was defined as a ≥3‐point worsening on the Scandinavian Stroke Scale during the first 48 h after randomization. Blood samples were analyzed for D‐dimer, prothrombin fragment 1 + 2, soluble fibrin monomer, and C‐reactive protein. Results – A total of 382 patients were included in the analyses. Levels of D‐dimer and other markers of hemostatic activation were not significantly higher in patients with stroke progression than in other patients (D‐dimer median values: 1025 ng/ml vs 970 ng/ml, P = 0.73). The same was true for recurrent stroke (D‐dimer: 720 ng/ml vs 973 ng/ml, P = 0.96), and the combined endpoint of stroke progression, recurrent stroke, and death (D‐dimer: 991 ng/ml vs 970 ng/ml, P = 0.91). Multivariable analyses did not alter the results. Conclusion – D‐dimer and other markers of hemostatic activation were not associated with stroke progression, recurrent stroke, or death in patients with acute ischemic stroke and atrial fibrillation.