Localization and action of Dragon (repulsive guidance molecule b), a novel bone morphogenetic protein coreceptor, throughout the reproductive axis

Bone morphogenetic proteins (BMPs) play important roles in reproduction including primordial germ cell formation, follicular development, spermatogenesis, and FSH secretion. Dragon, a recently identified glycosylphosphatidylinositol-anchored member of the repulsive guidance molecule family, is also a BMP coreceptor. In the present study, we determined the tissue and cellular localization of Dragon in reproductive organs using immunohistochemistry and in situ hybridization. Among reproductive organs, Dragon was expressed in testis, epididymis, ovary, uterus, and pituitary. In the testis of early postnatal mice, Dragon was found in gonocytes and spermatogonia, whereas in immature testes, Dragon was only weakly expressed in spermatogonia. Interestingly, pregnant mare serum gonadotropin treatment of immature mice robustly induced Dragon production in spermatocytes. In adult testis, Dragon was found in spermatocytes and round spermatids. In the ovary, Dragon was detected exclusively within oocytes and primarily those within secondary follicles. In the pituitary, Dragon-expressing cells overlapped FSH-expressing cells. Dragon was also expressed in a number of cell lines originating from reproductive tissues including Ishikawa, Hela, LbetaT2, MCF-7, and JEG3 cells. Immunocytochemistry and gradient sucrose ultracentrifugation studies showed Dragon was localized in lipid rafts within the plasma membrane. In reproductive cell lines, Dragon expression enhanced signaling of exogenous BMP2 or BMP4. The present studies demonstrate that Dragon expression is dynamically regulated throughout the reproductive tract and that Dragon protein modulates BMP signaling in cells from reproductive tissues. The overlap between Dragon expression and the functional BMP signaling system suggests that Dragon may play a role in mammalian reproduction.     

Role of novel markers of inflammation in patients with stable coronary heart disease

The role of novel markers of inflammation in patients with coronary heart disease (CHD) is still unclear. We conducted a case-control study to assess the association between various markers of inflammation and the presence and severity of chronic stable CHD. We included 312 clinically stable patients with angiographically documented CHD, aged 40 to 68 years. Voluntary blood donors (n = 479) matched for age and gender served as controls. High-sensitivity C-reactive protein, serum amyloid A, plasminogen activator inhibitor-1 activity, von Willebrand factor, fibrinogen, plasma viscosity, albumin, and neutrophils were determined. The severity of CHD was evaluated by 3 coronary scoring systems: the clinical 1- to 3-vessel disease score, the American Heart Association extension score (1 to 15 segments), and the Gensini score. All markers of inflammation were highly significantly elevated (all p <0.005) in patients with stable CHD compared with controls. After multivariable adjustment by means of logistic regression analysis, the association between CHD and fibrinogen, plasma viscosity, von Willebrand factor, and plasminogen activator inhibitor-1 activity remained substantial, whereas it decreased in high-sensitivity C-reactive protein, serum amyloid A, and neutrophils. The combination of > or = 2 markers of inflammation was associated with a strongly increased risk of CHD. No association between markers of inflammation and any of the coronary scores applied was found. These results document an independent association between most of the markers of inflammation and chronic CHD, even in clinically stable patients. The combination of several of these biochemical markers, i.e., the determination of an "inflammatory risk profile," may be useful to further stratify cardiovascular risk.     

Use of computed axial tomography to diagnose vascular ring in an infant

Computed axial tomography was performed in an infant with severe respiratory distress. A right aortic arch and paratracheal density was visualized, suggesting a vascular ring. Angiography confirmed a right aortic arch, mirror-image branching, and a left patent ductus arteriosus.     

Resistance to antiplatelet therapy

Cardiovascular mortality continues to be high and events continue to occur in patients taking antiplatelet medications. Aspirin and clopidogrel have become integral parts of management in patients with coronary artery disease and after percutaneous angioplasty. However, the platelet responses to aspirin and clopidogrel are not uniform. Diminished or lack of response to these agents has been termed aspirin resistance and clopidogrel resistance. These phenomena have tremendous clinical significance as together they may occur in more than 50% of all patients on chronic therapy with aspirin or clopidogrel. Postulated mechanisms of aspirin and clopidogrel resistance include alterations in genetic, pharmacokinetic, and platelet properties. There is a dearth of information in regard to their clinical significance, methods to test them, and strategies to treat them. Further research is necessary in these areas to identify these patients and treat them appropriately.     

Hydatid Cyst of the Liver Rupturing into the Biliary Tract—Mimicking Acute Cholecystitis on Hepatobiliary Scanning

Two patients presenting with right upper abdominal colicky pain, jaundice, and fever had a hepatobiliary scan using Tc 99m HIDA. The scan was suggestive of acute cholecystitis and a space occupying lesion in the liver. On operation, liver echinococcosis, located in the right lobe rupturing into the biliary ductal system, was found. Intraoperative cholangiography revealed filling defects in the main biliary ducts. Exploration of the common bile duct disclosed daughter cysts and cystic debris. Acute cholecystitis or stones were not found. We conclude that in patients with a clinical picture and HIDA scanning compatible with acute cholecystitis and a space occupying lesion in the liver, the diagnosis of hydatid cyst of the liver which has ruptured into the biliary tract should be considered.     

Double aortic arch system producing obstruction to left ventricular outflow

The occurrence of a double aortic arch system with intracardiac defects is unusual. Clinical recognition may be difficult in the absence of upper airway obstruction. This report describes the diagnosis and surgical management of an infant with Interruption of the ventral left arch and hypoplasia of the dorsal right arch who presented with evidence of pulmonary and systemic venous congestion caused by obstruction to left ventricular outflow and a large left to right ventricular shunt.