Cardiac Integrins: The Ties That Bind Simpson, David G.; Reaves, Titus A.; Shih, Daw-tsun ...
Cardiovascular pathology,
05/1998, Letnik:
7, Številka:
3
Journal Article
Recenzirano
An elaborate series of morphogenetic events must be precisely coordinated during development to promote the formation of the elaborate three-dimensional structure of the normal heart. In this study ...we focus on discussing how interconnections between the cardiac myocyte and its surrounding environment regulate cardiac form and function. In vitro experiments from our laboratories provide direct evidence that cardiac cell shape is regulated by a dynamic interaction between constituents of the extracellular matrix (ECM) and by specific members of the integrin family of matrix receptors. Our data indicates that phenotypic information is stored in the tertiary structure and chemical identity of the ECM. This information appears to be actively communicated and transduced by the α1β1 integrin molecule into an intracellular signal that regulates cardiac cell shape and myofibrillar organization. In this study we have assessed the phenotypic consequences of suppressing the expression and accumulation of the α1 integrin molecule in aligned cultures of cardiac myocytes. In related experiments we have examined how the overexpression of α2 and α5 integrin, integrins normally not present or present at very low copy number on the cell surface of neonatal cardiac myocytes, affect cardiac protein metabolism. We also consider how biochemical signals and the mechanical signals mediated by the integrins may converge on common intracellular signaling pathways in the heart. Experiments with the whole embryo culture system indicate that angiotensin II, a peptide that carries information concerning cardiac load, plays a role in controling cardiac looping and the proliferation of myofibrils during development.
Endovascular treatment options for vascular injury in pediatric patients are quite limited owing to concerns regarding long-term durability and the lack of devices suitable for the pediatric anatomy. ...However, in rare circumstances, open surgical therapy will not be an option, and patients will require unconventional endovascular solutions for lifesaving or limb-saving therapies. In the present report, we describe an endovascular treatment of a pediatric patient for whom initial surgical management of a blunt abdominal aortic injury had failed, with subsequent development of an aortic pseudoaneurysm. A 10-year-old girl had presented after a high-speed motor vehicle accident with a seatbelt sign. Multiple abdominal injuries were identified, including blunt aortic injury, significant devitalization of the small bowel, colonic perforation with fecal contamination, multiple lumbar spine fractures, and pulmonary contusions. The patient developed bilateral lower extremity ischemia from the aortic injury and had initially undergone open repair. One month later, the patient had developed a pseudoaneurysm of the aorta near the aortic bifurcation. Because of the hostile abdomen and ensuing short gut syndrome, the pseudoaneurysm was managed using endovascular techniques. The limb of an Excluder internal iliac branch endoprosthesis (W.L. Gore & Associates, Flagstaff, AZ) was used as the endograft. The aortic bifurcation was raised and reconstructed using four Viabahn self-expanding stents (W.L. Gore & Associates). The completion angiogram showed complete resolution of the pseudoaneurysm. The follow-up computed tomography angiogram showed widely patent stent grafts with complete resolution of the pseudoaneurysm. Endovascular management of traumatic vascular injuries in pediatric patients is feasible. The likelihood of reintervention in the future is high with patient growth. However, it is a viable option in lifesaving or limb-saving situations in which open repair is high risk.
Background Autonomous secretion of aldosterone in patients with primary aldosteronism increases glomerular filtration rate and causes kidney damage. The influence of a mild decrease in kidney ...function on residual hypertension after adrenalectomy is unexplored. Study Design Nonconcurrent prospective study. Setting & Participants The study was based on the Taiwan Primary Aldosteronism Investigation (TAIPAI) database. 150 patients (61 men; overall mean age, 47.2 ± 11.6 years) with a diagnosis of aldosterone-producing adenoma had undergone unilateral adrenalectomy at National Taiwan University Hospital from July 1999 to January 2007. Predictor Presurgery estimated glomerular filtration rate (eGFR). Outcomes & Measurements Residual hypertension after adrenalectomy, defined either as less than 75% of recorded blood pressure measurements with systolic blood pressure less than 140 mm Hg and diastolic blood pressure less than 90 mm Hg or requiring antihypertensive medications during the first year after surgery. Results Before surgery, 27 (18%), 72 (48%), and 51 (34%) patients had moderately to severely decreased (<60 mL/min/1.73 m2 ), mildly decreased (60 ≤ eGFR < 90 mL/min/1.73 m2 ), or nondecreased eGFR (≥90 mL/min/1.73 m2 ), respectively. After surgery, 16 (59.3%), 29 (40.3%), and 10 (19.3%) patients in each category had postsurgery residual hypertension. Compared with patients without decreased eGFR before surgery, adjusted odds ratios for postsurgery residual hypertension were 2.7 (95% confidence interval, 1.03 to 7.0; P = 0.04) and 2.8 (95% confidence interval, 1.05 to 9.3) for mildly and moderately to severely decreased eGFR, respectively. Limitations Arbitrary definition for residual hypertension. Conclusions Two-thirds of patients with aldosterone-producing adenoma were cured of hypertension by means of unilateral adrenalectomy. Kidney function impairment, even mild, appears to be associated with a high incidence of postsurgery residual hypertension.
The goal of ovarian cancer screening is to detect disease when confined to the ovary (stage I) and thereby prolong survival. We believe this is an elusive goal because most ovarian cancer, at its ...earliest recognizable stage, is probably not confined to the ovary. We propose a new model of ovarian carcinogenesis based on clinical, pathological, and molecular genetic studies that may enable more targeted screening and therapeutic intervention to be developed. The model divides ovarian cancer into 2 groups designated type I and type II. Type I tumors are slow growing, generally confined to the ovary at diagnosis and develop from well-established precursor lesions so-called borderline tumors. Type I tumors include low-grade micropapillary serous carcinoma, mucinous, endometrioid, and clear cell carcinomas. They are genetically stable and are characterized by mutations in a number of different genes including KRAS, BRAF, PTEN , and beta-catenin . Type II tumors are rapidly growing, highly aggressive neoplasms that lack well-defined precursor lesions; most are advanced stage at, or soon after, their inception. These include high-grade serous carcinoma, malignant mixed mesodermal tumors (carcinosarcomas), and undifferentiated carcinomas. The type II tumors are characterized by mutation of TP53 and a high level of genetic instability. Screening tests that focus on stage I disease may detect low-grade type I neoplasms but miss the more aggressive type II tumors, which account for most ovarian cancers. A more rational approach to early detection of ovarian cancer should focus on low volume rather than low stage of disease.
We report the case of a 23-year-old female pedestrian who had been struck by a car and had presented with axillary artery transection in the setting of scapulothoracic dissociation. The initial ...endovascular repair was compromised by her shoulder instability and had required the addition of bridging stent placement. Caution is advised with endovascular repair in this clinical scenario because of possible stent separation.
Background The reconstruction of outflow is a crucial step in living donor liver transplantation. This study describes a suitable technique that uses synthetic vascular conduits in presence of ...multiple draining veins of right lobe of liver and the outcome of the recipients to evaluate safety of using multiple synthetic grafts. Methods From March 2011 to September 2014, 325 patients underwent right lobe living donor liver transplantation. Expanded polytetra-fluoroethylene (ePTFE) grafts were used in total 155 of the liver allografts. Among these, 16 liver grafts required dual ePTFE grafts to reconstruct the outflow due to presence of multiple hepatic veins. Results The mean diameters for venous branches of segment 5 (V5) and 8 (V8) were 5 mm (range, 4–8 mm) and 7 mm (range, 5–9 mm). The mean diameter of inferior right hepatic veins was 8 mm (7–10 mm). All the recipients who received the right liver with dual ePTFE grafts showed satisfactory inflow and outflow immediately after reconstruction as measured by Doppler flowmetry. Postoperative ultrasonographic studies showed no disturbances in outflow. Protocol dynamic computed tomography performed in the second postoperative month showed 100% patency rates of the artificial grafts. At median follow-up of 24 months graft survival was achieved in 88%, whereas the patency rates of the ePTFE grafts were 100%. Conclusion The use of “V-Plasty” technique using dual artificial vascular grafts is a safe and feasible technique in the presence of various allograft venous anomalies & ensures a single venous channel for outflow reconstruction. Our study also suggests that ePTFE graft may be a useful interposition material without serious complications.
This study evaluated the efficacy and toxicity of proton therapy for functional pituitary adenomas (FPAs).
We analyzed 165 patients with FPAs who were treated at a single institution with proton ...therapy between 1992 and 2012 and had at least 6 months of follow-up. All but 3 patients underwent prior resection, and 14 received prior photon irradiation. Proton stereotactic radiosurgery was used for 92% of patients, with a median dose of 20 Gy(RBE). The remainder received fractionated stereotactic proton therapy. Time to biochemical complete response (CR, defined as ≥ 3 months of normal laboratory values with no medical treatment), local control, and adverse effects are reported.
With a median follow-up time of 4.3 years (range, 0.5-20.6 years) for 144 evaluable patients, the actuarial 3-year CR rate and the median time to CR were 54% and 32 months among 74 patients with Cushing disease (CD), 63% and 27 months among 8 patients with Nelson syndrome (NS), 26% and 62 months among 50 patients with acromegaly, and 22% and 60 months among 9 patients with prolactinomas, respectively. One of 3 patients with thyroid stimulating hormone-secreting tumors achieved CR. Actuarial time to CR was significantly shorter for corticotroph FPAs (CD/NS) compared with other subtypes (P=.001). At a median imaging follow-up time of 43 months, tumor control was 98% among 140 patients. The actuarial 3-year and 5-year rates of development of new hypopituitarism were 45% and 62%, and the median time to deficiency was 40 months. Larger radiosurgery target volume as a continuous variable was a significant predictor of hypopituitarism (adjusted hazard ratio 1.3, P=.004). Four patients had new-onset postradiosurgery seizures suspected to be related to generously defined target volumes. There were no radiation-induced tumors.
Proton irradiation is an effective treatment for FPAs, and hypopituitarism remains the primary adverse effect.
With the introduction of version 2.73, several new patient risk factors are now captured in The Society of Thoracic Surgeons' (STS) Adult Cardiac Surgery Database. We sought to evaluate the potential ...association of these risk factors with mortality.
We reviewed all patients with an STS predicted risk of mortality in our statewide quality collaborative database from July 2011 to September 2013 (N = 19,743). Univariate analyses were used to determine significant associations between mortality and the new risk factors in version 2.73. We then performed multivariable analysis, incorporating the STS predicted risk of mortality into our regression.
In the univariate model, patients with illicit drug use, syncope, unresponsive neurologic state, cancer within the last 5 years, current smoking history, other tobacco use, or sleep apnea had no significant difference in mortality (p > 0.05). Patients with liver disease, elevated Model for End-Stage Liver Disease score, mediastinal radiation, prolonged 5-meter walk test, home oxygen use, inhaled medications or bronchodilator therapy, decreased forced expiratory volume, and history of recent pneumonia had significant increases in operative mortality (p < 0.05). In multivariable analysis incorporating the STS predicted risk models, liver disease, elevated Model for End-Stage Liver Disease score, prolonged 5-meter walk test, home oxygen use, bronchodilator therapy, and abnormal pulmonary function tests were independently predictive of mortality.
Several of the new STS data variables were significantly associated with operative mortality after cardiac surgery. The addition of these patient factors improves our understanding of evolving patient demographics and comorbid conditions and their impact on perioperative risk. This will improve both shared decision making and assessments of provider performance.
Mice with deletion of insulin receptor substrate (IRS)-1 (IRS-1 knockout KO mice) show mild insulin resistance and defective glucose-stimulated insulin secretion and reduced insulin synthesis. To ...further define the role of IRS-1 in islet function, we examined the insulin secretory defect in the knockouts using freshly isolated islets and primary beta-cells. IRS-1 KO beta-cells exhibited a significantly shorter increase in intracellular free Ca(2+) concentration (Ca(2+)(i)) than controls when briefly stimulated with glucose or glyceraldehyde and when l-arginine was used to potentiate the stimulatory effect of glucose. These changes were paralleled by a lower number of exocytotic events in the KO beta-cells in response to the same secretagogues, indicating reduced insulin secretion. Furthermore, the normal oscillations in intracellular Ca(2+) and O(2) consumption after glucose stimulation were dampened in freshly isolated KO islets. Semiquantitative RT-PCR showed a dramatically reduced islet expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)-2b and -3 in the mutants. These data provide evidence that IRS-1 modulation of insulin secretion is associated with Ca(2+) signaling and expression of SERCA-2b and -3 genes in pancreatic islets and provides a direct link between insulin resistance and defective insulin secretion.
PDF
