ABSTRACT
Objective@#To analyze the phenotype and genotype of a Chinese pedigree with inherited dysfibrinogenaemia and investigate the molecular mechanism of the disease. @*Methods@#Venous blood samples were collected from all family members, and routine coagulation tests were conducted. Functional fibrinogen in venous blood samples was measured by Clauss method, and the antigen level of fibrinogen in plasma was measured by immunoturbidimetry assay. All the exons and exon-intron boundaries of the three fibrinogen genes were analyzed by direct sequencing. Fibrinogen electrophoresis, fibrinogen clottability measurement, fibrin polymerisation measurement and electron microscopy scanning were also used to investigate the molecular characteristics and pathogenesis. @*Results@#The proband had normal activated partial thromboplastin time, prothrombin time and plasma fibrinogen antigen, but prolonged thrombin time, prolonged reptilase time and reduced fibrinogen activity level, which were also found in his father. The sequencing results of the proband revealed heterozygous A1211G in the exon 2 of FGA gene originating from his father, which caused Arg19Gly missense mutation. The western-blot results showed that no abnormal bands of plasma fibrinogen were found in the proband and his father. Both thrombin-induced fibrin polymerisation and reptilase induced fibrin polymerisation were significantly impaired compared to normal control. Fibrinogen clottability measurement showed that only about 20.8% molecules of plasma fibrinogen in the proband were involved in the clot formation. Scanning electron microscopy revealed that the proband′s average fibre diameters were found to be significantly thicker than that of the control(P＜0.001), and the density was smaller than that of normal control. @*Conclusion@#The Arg19Gly mutation should be responsible for the proband′s dysfibrinogenaemia and the relevant clinical symptoms.
ABSTRACT
Aim To investigate the role of locus coeruleus(LC)-norepinephrinergic system and sympathetic nervous system in immunosuppression under cold stress, using 6-hydroxydopamine(6-OHDA) as chemical sympathectomy.Methods Rats were maintained in cold chamber at 4℃ for 4 h.The 51Cr release assay from YAC-1 cells was used to determine the splenic NK cell activity, the double staining of ABC method was employed to observe the immunoreactive expression of Fos, arginine-vasopressin(AVP), oxytocin(OT) and tyrosine hydroxylase(TH), and conventional radioimmunoassay was used to measure plasma corticosterone (CORT) concentrations.Results Central sympathectomy with intracerebroventricular(i.c.v.) injection of 6-OHDA r educed significantly the elevation of plasma corticosterone level, the expressio n of Fos in hypothalamic paraventricular nucleus(PVN) and in locus coeruleus(LC ), as well as the suppression of NK activity induced by cold stress at 4℃ for 4 h. Peripheral sympathectomy with intraperitoneal (i.p.) injection of 6-OHDA al so reversed the cold stress-induced suppression of NK cytotoxicity, but without significant effect on Fos expression in brain. Double staining showed that amon g the Fos-positive neurons in PVN only a few co-expressed Fos and AVP or Fos a nd OT, while in LC the majority of Fos-positive neurons co-expressed Fos and T H.Conclusion The mechanism of suppression of NK activity induce d by cold stress may be mediated through HPA axis activated partially by central LC-norepinephrinergic system and through the peripheral sympathetic nervous system.
ABSTRACT
AIM To investigate the effect of clonidine on intraocular pressure(IOP) and the possible role in which ? adrenergic mechanism plays. METHODS The change on IOP was observed following clonidine administered via three different routes: (1)clonidine topically administered to eyes; (2)clonidine intracerebroventricularly injected (icv)or topically administered after yohimbine or prazosin icv; (3)microinjection of clonidine into locus coeruleus(LC). RESULTS Clonidine decreased IOP significantly, ? 2 adrenoceptor antagonist, but not ? 1 adrenoceptor antagonist, can reverse the decreasing effect on IOP caused by clonidine icv and administered topically. CONCLUSION Clonidine administered both topically or intracranially can decrease IOP;? 2 adrenoceptor in central nervous system is involved in this effect.