Capacity of human serum to depolymerize actin filaments

Human blood depolymerizes filamentous (F-)actin. The interaction of actin filaments and monomers with human serum was studied by following the kinetics and extent of the depolymerization of pyrene-labeled F- actin and by analysis of serum proteins adhering to immobilized actin monomers. In physiologic Ca2+ concentrations, the depolymerization of F- actin proceeds in two stages: a rapid phase, attributed to direct severing of filaments by plasma gelsolin, and a slow phase attributed to the binding of actin monomers to vitamin D-binding protein (DBP). Without Ca2+, only the slow phase is observed. Human serum can completely depolymerize 10 to 18 mumol/L of actin, of which approximately 5 mumol/L occurs rapidly. Depolymerization can be accounted for by the normal serum concentrations of gelsolin and DBP. Fibrin(ogen) and fibronectin, which bind actin in vitro, do not contribute to the kinetics or extent of its depolymerization. Affinity chromatography and functional assays for the presence of gelsolin-actin complexes show that addition of G-actin to serum results in preferential formation of actin-DBP complexes, but that addition of F- actin to serum produces both gelsolin-actin complexes and DBP-actin complexes. The distinctive binding of actin monomers and polymers to these two serum proteins suggests a means by which their coordinated actions are maximized in vivo, from the standpoint of depolymerizing filaments and clearing monomers from the circulation.     

Altered phosphate metabolism in myocardial infarction: P-31 MR spectroscopy

The high-energy myocardial phosphate metabolism of four patients with acute anterior myocardial infarction after coronary angioplasty and drug therapy was evaluated with cardiac-gated phosphorus magnetic resonance (MR) depth-resolved surface coil spectroscopy (DRESS) 5-9 days after the onset of symptoms. Significant reductions (about threefold) in the phosphocreatine (PCr) to inorganic phosphate (Pi) ratio and elevations in the Pi to adenosine triphosphate (ATP) ratio were observed in endocardially or transmurally derived MR spectra when compared with values from epicardially displaced spectra and values from seven healthy volunteers (P less than .05). High-energy phosphate metabolites and Pi ratios did not vary significantly during the cardiac cycle in healthy volunteers. However, contamination of Pi resonances by phosphomonoester components, including blood 2,3-diphosphoglycerate, precluded accurate spectral quantification of Pi and pH. The results indicate that localized P-31 MR spectroscopy may be used to directly assess cellular energy reserve in clinical myocardial infarction and to evaluate metabolic response to interventions.     

Incorporation versus infection of retroperitoneal aortic grafts: MR imaging features

The magnetic resonance (MR) imaging characteristics of normal aortic graft healing were compared with those of perigraft infection in 57 patients after aortic graft implantation. Thirty-three patients without postoperative complications underwent MR imaging in a 0.35-T unit 1 week after graft implantation, and 13 of those patients were reexamined 2-3 months after graft implantation. Twenty-four patients with clinically suspected perigraft infection underwent MR imaging 6 weeks to 18 years after graft implantation. Early normal postoperative changes were characterized by a perigraft collar of low to medium signal intensity on T1-weighted images and of high intensity on T2-weighted images in all 33 cases, consistent with perigraft fluid collection. In 10 of 13 patients reexamined 2-3 months postoperatively, the MR images demonstrated a collar of tissue consistent with perigraft fibrosis. In cases of clinical suspicion of retroperitoneal graft infection, MR imaging showed eccentric fluid collections of low to medium signal intensity on T1-weighted images and high intensity on T2-weighted images at more than 3 months after surgery. The MR findings were diagnostic of retroperitoneal perigraft infection in 17 of 20 patients shown to be infected at surgery. Retroperitoneal infection was correctly excluded on the basis of MR findings in four patients. Thus, MR imaging is an accurate imaging method for the diagnosis of aortic graft infection. In the early postoperative phase, resolving perigraft fluid cannot be differentiated from perigraft infection.     

Abrupt cessation of clonidine administration: A prospective study

In 20 patients with mild to moderate hypertension, the effects of abrupt cessation of clonidine therapy on blood pressure, heart rate and catecholamine excretion were evaluated. In a double blind, crossover study, placebo was substituted for clonidine after 3 days of therapy and again after 30 days. The results demonstrated no instances of clinically significant symptoms or overshoot in blood pressure or heart rate. There was an overshoot in norepinephrine excretion that approached the upper limits of normal. Thus, a clinical withdrawal syndrome associated with abrupt cessation of clonidine was not seen in this study of patients without severe hypertension who were given the drug without a diuretic agent.     

Long-Term Evaluation of Fenoterol by Two Different Modes of Administration (Oral versus Metered Aerosol)

Thirteen asthmatic children were treated double-blind for 6 weeks each with either inhaled or oral fenoterol (a β-2-selective adrenergic bronchodilator) three times a day. The oral dose regimen resulted in superior bronchodilation on the basis of peak expiratory flow rates, although clinical symptom scores did not differ with the route of administration. We conclude that oral fenoterol can be used on a chronic basis for the treatment of moderate asthmatics. Doses of inhaled fenoterol higher than 0.4 mg three times per day used in this study may be required to produce a similar effect to 0.8 mg/kg of oral fenoterol in three divided doses.     

Lasting safe interruption of endarterectomy thrombosis by transiently infused antithrombin peptide D-Phe-Pro-ArgCH2Cl in baboons

To evaluate the relative antithrombotic efficacy and hemostatic safety of antithrombin therapy for vascular thrombus formation at sites of mechanical vascular injury, we administered the potent and specific irreversible synthetic antithrombin D-PHE-PRO-ARG chloromethyl ketone (D-FPRCH2Cl) after performing carotid endarterectomies in baboons. The continuous intravenous infusion of D-FPRCH2Cl, 100 nmol/kg per minute for 1 hour, abolished acute carotid endarterectomy thrombosis for at least 48 hours. The plasma level of D-FPRCH2Cl during the infusion was maintained steady at 7.2 +/- 0.9 mumol/L, but decreased rapidly after discontinuing its infusion (T50 17 minutes). Platelet deposition, measured in real time using autologous 111In-platelet scintillation camera imaging, was 1.51 +/- 0.40 x 10(8) platelet/cm in the 14 treated animals 90 minutes postoperatively, compared with 11.7 +/- 1.16 x 10(8) platelet/cm in 14 heparin-treated controls (P < .002). The antithrombotic benefit was equivalent for treatment begun either 5 minutes before (nine animals) or 15 minutes after (five animals) reestablishing flow in the operated vessel, ie, 1.59 +/- 0.36 x 10(8) platelet/cm versus 1.35 +/- 0.51 x 10(8) platelet/min, respectively; P > .5. Endarterectomy thrombosis remained decreased for at least 48 hours postoperatively, as determined by the ratio between net 111In- platelet radioactivity at the endarterectomized site versus whole blood (ratio 0.82 +/- 0.25 in the treatment group v 3.03 +/- 0.51 in heparin controls at 90 minutes, P < .005; and 0.85 +/- 0.23 v 3.25 +/- 0.48 at 48 hours, P < .002). The marked reduction in endarterectomy thrombosis in treated animals at 48 hours was confirmed by scanning electron microscopy. Thrombin activity formed rapidly and became immediately bound to thrombus on thrombogenic segments in untreated control studies; treatment with D-FPRCH2Cl irreversibly inactivated the thrombus-bound thrombin. Hemostatic function, as measured by bleeding time (BT), activated partial thromboplastin time (APTT), and prothrombin time (PT) was impaired throughout the intravenous administration of D-FPRCH2Cl (BT > 30 minutes, APTT > 150 seconds, PT > 50 seconds); BT, APTT, and PT values were normal 30 minutes after discontinuing the infusions. As expected, blood loss into the surgical wound was substantial in nine animals receiving therapy initiated before restoring flow in the operated vessel (mean 95 mL, range 45 to 130 mL). By contrast, beginning D-FPRCH2Cl therapy in five animals 15 minutes after restoring arterial flow, a time when surgical hemostasis had been achieved, prevented excessive blood loss (mean 15 mL, range 10 to 35 mL; P < .01 compared with earlier treatment) without compromising the antithrombotic effects.(ABSTRACT TRUNCATED AT 400 WORDS)     

Joubert综合征的CT和MRI诊断

目的 探讨Joubert综合征的CT和MRI表现。方法 回顾性分析10例Joubert综合征患儿临床、CT和MRI资料，10例均行CT平扫，其中4例同时行MR平扫。结果 Joubert综合征的典型影像学表现包括小脑半球间“中线裂”、“蝙蝠翼”状和“三角形”第4脑室，以及中脑水平的“磨牙征”。10例行CT检查者，均可见“中线裂”；其中9例显示“蝙蝠翼”状和“三角形”第4脑室，8例显示“磨牙征”。4例行MR检查者均显示上述征象。结论 Joubert综合征的CT和MRI表现具有特征性，结合临床可提供明确诊断。