Structural basis for p50RhoGAP BCH domain-mediated regulation of Rho inactivation.

Spatiotemporal regulation of signaling cascades is crucial for various biological pathways, under the control of a range of scaffolding proteins. The BNIP-2 and Cdc42GAP Homology (BCH) domain is a highly conserved module that targets small GTPases and their regulators. Proteins bearing BCH domains are key for driving cell elongation, retraction, membrane protrusion, and other aspects of active morphogenesis during cell migration, myoblast differentiation, and neuritogenesis. We previously showed that the BCH domain of p50RhoGAP (ARHGAP1) sequesters RhoA from inactivation by its adjacent GAP domain; however, the underlying molecular mechanism for RhoA inactivation by p50RhoGAP remains unknown. Here, we report the crystal structure of the BCH domain of p50RhoGAP Schizosaccharomyces pombe and model the human p50RhoGAP BCH domain to understand its regulatory function using in vitro and cell line studies. We show that the BCH domain adopts an intertwined dimeric structure with asymmetric monomers and harbors a unique RhoA-binding loop and a lipid-binding pocket that anchors prenylated RhoA. Interestingly, the ß5-strand of the BCH domain is involved in an intermolecular ß-sheet, which is crucial for inhibition of the adjacent GAP domain. A destabilizing mutation in the ß5-strand triggers the release of the GAP domain from autoinhibition. This renders p50RhoGAP active, thereby leading to RhoA inactivation and increased self-association of p50RhoGAP molecules via their BCH domains. Our results offer key insight into the concerted spatiotemporal regulation of Rho activity by BCH domain-containing proteins.

Clinical value of tumor markers SCCA,TPS,NSE and CYFERA21-1 detection in diagnosis of lung cancer / 国际检验医学杂志

Objective To explore the clinical value of tumor marker squamous cell carcinoma antigen(SCCA) ,tissue polypeptide specific antigen(TPS) ,neuron‐specific enolase(NSE) ,cytokeratin fragment 19(CYFRA21‐1) detections in the patient with lung cancer .Methods 70 patient with newly diagnosed lung cancer(including 26 cases of squamous cell carcinoma ,23 cases of adenocar‐cinoma and 21 cases of small cell carcinoma) ,40 cases of lung benign diseases and contemporaneous 30 individuals undergoing the physical examination were randomly selected as the lung cancer group ,lung benign disease group and healthy control group respec‐tively .Serum tumor markers of SCCA ,TPS ,NSE and CYFERA21‐1 were detected in all cases .Then the detection results were per‐formed the statistical analysis .Results The levels of SCCA ,TPS ,NSE and CYFERA21‐1 in the lung cancer group were significant‐ly higher than those in the lung benign diseases group and healthy control group ,the differences were statistically significant (P0 .05) .The combination detection of SCCA , TPS ,NSE and CYFERA21‐1 greatly increased the sensitivity and accuracy for diagnosing lung cancer .Conclusion The combina‐tion detection of SCCA ,TPS ,NSE and CYFERA21‐1 has very high clinical value for the diagnosis ,pathological typing and assisted clinical therapy of lung cancer .

Study the significance of blood VEGF,PAPP-A,D-D and urinary NAG/Cr ratio in patients with PIH / 国际检验医学杂志

Objective To study the clinical significance of changes of blood contents of vascular endothelial growth factors (VEGF).Pregnancy-associated plasma protein-A(PAPP-A),D-dimers(D-D)and Urinary N-acetyl-β-D-glucosaminidase/Creatinine (NAG/Cr)Ratio in patients with Pregnancy Induced Hypertension syndrome(PIH).Methods Serum VEGF and PAPP-A(with ELISA),plasma D-dimers(with biochemistry)and NAG/Cr(with velocity)contents were measured in 92 pregnant women with PIH and 35 controls.Results The serum VEGF contents in patients with PIH were significantly lower than those in controls(P<0.01)while PAPP-A,D-dimers and NAG/Cr contents were significantly higher(P<0.01).Those changes were especially marked in patients with advanced diseases.Conclusion Changes of blood contents of VEGF,PAPP-A D-dimers and Urinary NAG/Cr Ratio were closely related with the disease process of PIH.Determination of these changes was of clinical diagnostic as well as prognostic value.

Experience of Clinical Pharmacists Participating in Anti-infection Treatment in Intensive Care Unit / 中国药房

OBJECTIVE:To explore clinical pharmacists participating in anti-infection therapy in intensive care unit(ICU).METHODS:The typical cases of clinical pharmacists participating in anti-infection treatment in ICU were analyzed.RESULTS&CONCLUSION:Clinical pharmacists developed pharmaceutical care for anti-infection treatment in ICU and helped physicians to design individualized dosage regimen.It can improve the safety and effectiveness of antimcrobials in ICU patients and reflect the role of clinical pharmacists in rational use of drug.

Drug-resistance of Commonly Encountered Pathogens and Irrational Use of Antibiotics / 中华医院感染学杂志

OBJECTIVE To study the drug-resistance of commonly encountered pathogens and the manifestations of irrational use of antibiotics,in order to provide the gist for clinical therapy.METHODS The retrospective analysis on the drug-resistance of commonly encountered pathogens that isolated from clinical samples and records of(irrational) use of antibiotics from Jan 2004 to Jon 2005 were carried out.RESULTS Among 870 isolates,the first five kinds of pathogens were Pseudomonas aeruginosa(17.47%),Klebsiella pneumoniae(9.66%),Acinetobacter baumannii(8.85%),Escherichia coli(7.36%)and Candida albicans(11.95%).They had resistance to the commonly used(antibiotics) in various degrees.In 4 462 records,there were 659 records of irrational use of (antibiotics),occupied 14.77%.CONCLUSIONS It is important that to strengthen the management of antibiotics(usage) and institutions in hospitals,to inform doctor the drug-resistance trend,based on the result of drug(sensitivity) test,in order to use antibiotics more rationally and reduce the appearance of drug-resistant bacteria.

Compound Danshen Injection-induced Adverse Reactions and the Prevention and Cure Measures / 中国药房

OBJECTIVE:To discuss the adverse reactions induced by compound danshen injection and the preventon and cure measures so as to offer basis for the clinic in the rational use of drugs.METHODS:Compound dansen injection-induced ADR cases reported in the internal pharmaceutical journals retrieved from1997to2005were collected and analyzed statisti-cally.RESULTS:Compound danshen injection could induce multisystem adverse reactions,immune system,cardiovascular system,digestive system,urinary system and nervous system,particularly the allergic reactions.CONCLUSION:Clinicians should know the characteristics of adverse reactions induced by compound danshen injection so as to apply it rationally.