51 research outputs found

    SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras

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    SHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function. Solving the structure of the SHANK3 N-terminal region revealed that the SPN domain is an unexpected Ras-association domain with high affinity for GTP-bound Ras and Rap G-proteins. The role of Rap1 in integrin activation is well established but the mechanisms to antagonize it remain largely unknown. Here, we show that SHANK1 and SHANK3 act as integrin activation inhibitors by sequestering active Rap1 and R-Ras via the SPN domain and thus limiting their bioavailability at the plasma membrane. Consistently, SHANK3 silencing triggers increased plasma membrane Rap1 activity, cell spreading, migration and invasion. Autism-related mutations within the SHANK3 SPN domain (R12C and L68P) disrupt G-protein interaction and fail to counteract integrin activation along the Rap1-RIAM-talin axis in cancer cells and neurons. Altogether, we establish SHANKs as critical regulators of G-protein signalling and integrin-dependent processes

    Engineered Models of Metastasis with Application to Study Cancer Biomechanics

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    Three-dimensional complex biomechanical interactions occur from the initial steps of tumor formation to the later phases of cancer metastasis. Conventional monolayer cultures cannot recapitulate the complex microenvironment and chemical and mechanical cues that tumor cells experience during their metastatic journey, nor the complexity of their interactions with other, noncancerous cells. As alternative approaches, various engineered models have been developed to recapitulate specific features of each step of metastasis with tunable microenvironments to test a variety of mechanistic hypotheses. Here the main recent advances in the technologies that provide deeper insight into the process of cancer dissemination are discussed, with an emphasis on three-dimensional and mechanical factors as well as interactions between multiple cell types

    Diagnosis and Treatment of Penetrating Cardiac Injury One Year after Thoracic Stab Wound

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    In any patient with a history of penetrating thoracic trauma, cardiac injury must be kept in mind. Here, we describe a 36 years-old female referred to this hospital with severe chest pain and hypotension. After primary evaluation and suggestion of AMI, streptokinase was started for the patient and because of deterioration of vital signs, cardiac surgery consultation was requested. After performing urgent echocardiography, massive pericardial tamponade was detected. Visualization of a knife blade on C.X.R and past medical history of thoracic stab injury led to a diagnosis of delayed cardiac tamponade and urgent sternotomy was performed. The blade that had penetrated the right ventricular chamber was extracted. Six days after operation, patient was discharged without any problem. This case study suggests the importance of high suspicion to cardiac injury in any patient with chest pain and a history of chest trauma

    Effectiveness of Oral N-acetyl-cystein in Reduction of Pulmonary Complications in Smokers Undergoing Coronary Artery Bypass Surgery

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    Introduction: Up to 12% of patients undergoing coronary artery bypass graft have pulmonary complications. Smoking can cause a six-time increase in pulmonary complication after major surgery. The most common pulmonary changes after CABG are decrease in FRC, VC and atelectasis. In this study, the effect of oral N-acetyl-cystein in reduction of severity of hypoxemia and atelectasis in current smokers who smoked more than 10 packs/year and had undergone CABG was evaluated. Methods: In the study, 54 current smoker patients were selected randomly and allocated to two drug and placebo groups. In the study group, 300mg N-acetyl-cystein (ACC long) containing vitamin C was prescribed two times a day from 4 days before operation up to 3 days after surgery and in control group, effervescent vitamin C tablet was prescribed as placebo. Patients with body mass index more than 35, NYHA class IV, those who needed intra aortic balloon pump and those who needed reoperation due to bleeding were excluded from the study. In all patients, spirometry was done in the preoperative visit and FEV1/FVC was determined. Induction and maintenance of anesthesia was similar in all patients. Arterial blood gas samples were obtained immediately after anesthesia induction and 4 to 6 hours after extubation. Chest X ray was taken before, 6 to 10 hours after extubation and 3rd postoperative day. Severity of atelectasis was also measured. Quantitative & qualitative data was analyzed by ANOVA and Chi-square tests, respectively. Pvalue<0.05 was considered as statistically significant. Results: Both groups were similar with respect to demographic data including ejection fraction, NYHA class, FEV1/FVC, cigarette smoking and Lima harvesting. The ratio of arterial oxygen pressure to fraction of inspiratory oxygen Pao2/FIo2 was not significantly different after induction but this difference was strongly significant (Pvalue<0.005) after extubation. Duration of mechanical ventilation was significantly shorter in patients who had N-acetyl-cystein, but duration of ICU stay was similar. Linear and segmental atelectasis was significantly less in the study group. Conclusion: N-acetyl-cystein can improve oxygenation and ventilatory parameters in pathological lungs, but further studies with different doses and different situations are needed

    Risk factors of blood transfusion in patients undergoing off-pump coronary artery bypass

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    Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: One of the most important components of coronary artery bypass graft surgery is need for blood transfusion that increases morbidity and mortality. The aim of this study was to evaluate the factors affecting the need for blood transfusion during off pump coronary artery bypass (OPCAB) surgery.&quot;n&quot;nMethods: In this descriptive case control study 923 patients who had undergone OPCAB at Afshar Hospital in Yazd, Iran, from July 2008 to January 2010 were evaluated. The data was gathered from their records and was analyzed.&quot;n&quot;nResults: 54% of male and 79% of female patient need blood transfusion. Mean age in patients needed transfusion was 61.58&amp;plusmn;11.11 years and in other group was 60.27&amp;plusmn;10.98 years of the patients that needed transfusion (p= 0.08). 563 (61%) of the patients needed transfusion with the average of two units. The need for blood transfusion was higher in female gender (p&amp;lt; 0.0001), low hematocrit (p&amp;lt; 0.0001), diabetes (p&amp;lt; 0.001), hypertension (p&amp;lt; 0.025) and multiple grafts (p&amp;lt; 0.027). There were no significant differences in preoperative hemostasis tests, affection to hyperlipidemia, CVA or renal failure, antiplatelet drug administration and the application of left internal mammary artery between the transfusion and non transfusion groups.&quot;n&quot;nConclusion: In this study preoperative hematocrit was most important risk factor in transfusion in patients that underwent OPCAB. Female gender, preoperative low hematocrit, multiple grafts, diabetes and hypertension increased the rate of blood transfusion. According to the high prevalence of blood transfusion in OPCAB, considering factors that affect the transfusion rate is essential

    Detection and Identification of Toxoplasma gondii Type One Infection in Sheep Aborted Fetuses in Qazvin Province of Iran

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    Background: The aim of this study was to apply the nested-PCR and bioassay methods in detection and genotyping of Toxoplasma gondii infection in provided sheep aborted fetus samples from Qazvin Province of Iran. Methods: Eighteen sheep aborted fetal samples were studied by nested-PCR-RFLP, histopathologi&shy;cal observation and microbiological assay. Bioassay in mice was carried out by inoculating the brain samples intraperitoneally. Results: The results demonstrated the frequency of 66% infected sheep aborted fetal samples with T. gondii type one. Although we could not isolate any parasite from inoculated mice even after three pas&shy;sages, but it was confirmed histopathologically formation of cyst like bodies in prepared mice brain sections. Conclusion: The results of the performed nested-PCR and formation of brain cyst in inoculated mice exhibited that T. gondii type one infection might be considered as one of the major causative agents for abortion in ewes
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