Thymidylate synthase is localized to the nuclear periphery in the yeast Saccharomyces cerevisiae

To date, the organization of DNA precursor synthesis within eukaryotic cells remains unresolved. Previous studies have suggested the existence of a multienzyme complex that is responsible for DNA precursor synthesis and is associated with sites of replication within the nucleus. Contrasting this, other studies have proposed that DNA precursor synthesis occurs outside the nucleus. To further these studies, we have addressed the location where thymidylate synthase resides in yeast. Subcellular fractionation experiments indicate thymidylate synthase is associated with purified nuclei. Consistent with this, immunofluorescence analysis suggests that thymidylate synthase is situated at the nuclear periphery.     

Congenital erythrocytosis with elevated erythropoietin level: an incorrectly set "erythrostat"?

It is well documented that IL-6 plays a critical role in B cell terminal differentiation, and in mucosal sites it stimulates proliferation and large-scale secretion of immunoglobulin by B cells, especially those committed to IgA production. The close juxtaposition of IL-6 mRNA+ cells to plasma cells in the intestinal lamina propria supports the proposition that IL-6 production in situ is an important factor determining the outcome of antibody responses at that site. However, it has not been established previously whether exogenous IL-6 could boost antibody responses in the intestine if administered with a challenge antigen. Using a resected gut loop (Thiry-Vella loop) model, we have been able to demonstrate that in mice with double loops, antibody containing cell responses to lumenal administration of ovalbumin were 50% greater in loops given intralumenal recombinant IL-6 with the challenge antigen, than in loops challenged with antigen alone. This demonstrates the efficacy of IL-6 in promoting accumulation of antibody secreting cells in the gut, and suggests a potential therapeutic role for IL-6 to enhance responses to mucosal vaccines.     

Localization of the somatostatin sst2(a) receptor in human cerebral cortex, hippocampus and cerebellum

AIMS: To quantify birth prevalence and spectrum of congenital heart disease in the Island population of Malta, and compare these rates with previous studies. METHODS: All patients diagnosed as having congenital heart disease by echocardiography, cardiac catheterization, surgery or post-mortem by 1 year of age between 1990-1994 were included. There were 231 cases of live born congenital heart disease with a birth prevalence of 8.8/1000 live births. The commonest lesions were ventricular septal defect, pulmonary stenosis and tetralogy of Fallot. The rates of individual lesions were compared with two recent epidemiological studies with similar methodologies. RESULTS: Although the overall birth prevalence of congenital heart disease was similar in three studies, significantly higher rates of pulmonary stenosis, tetralogy of Fallot and double outlet right ventricle were found in Malta, all of which predispose to right ventricular outflow tract obstruction. In contrast, there were lower rates of lesions causing left ventricular outflow tract obstruction. A higher rate of ventricular septal defect was also found. The Maltese gene pool may contain an inherent predisposition towards lesions causing right ventricular outflow tract obstruction.     

Progressive scapulothoracic subluxation after fracture of the clavicle

Fracture of the clavicle is a common injury that usually heals without consequence. Instability of the scapulothoracic articulation does not usually occur. In this case, the scapulothoracic subluxation was not obvious at the time of injury, but progressively worsened over the following 2 weeks. Open reduction and internal fixation of the clavicle fracture restored stability to the shoulder girdle. The patient went on to regain full function of her injured extremity.     

Haemodynamic changes in portal hypertension: new insights in the pathogenesis and clinical implications

In man and experimental animals, portal hypertension with portal-venous collaterals, is associated with a hyperdynamic circulation, caused by peripheral vasodilatation, mainly in the splanchnic bed. This peripheral vasodilatation is clinically important, since it is thought to be responsible for the pathogenesis of complications of portal hypertension such as ascites, the hepatorenal syndrome and portal hypertensive gastropathy and colopathy. Many cirrhotic patients may not die primarily because of their hepatic dysfunction, but rather because of the consequences of the circulatory abnormalities which are secondary to the liver disease. Circulating hormonal vasodilators from intestinal origin such as glucagon, insufficiently cleared by the liver, are only partly responsible for these changes. Recent experimental data point to a role for an increased production of the locally acting potent vasodilator nitric oxide in the vascular wall, in the pathogenesis of the hyperdynamic circulation. Furthermore, nitric oxide seems to play an important role in the development of portal-venous collaterals. Modulation of the nitric oxide production might offer therapeutic options for the treatment of portal hypertension and its complications.     

Papillary carcinoma arising in thyroglossal duct cyst: a case report and review of the literature

While thyroglossal duct cysts are a frequent cause of cervical masses, carcinomas arising in thyroglossal duct remnants are rare. In this paper the Authors report a new case, which occurred in a young woman. The diagnosis of carcinomas in thyroglossal duct cysts almost always comes as a surprise upon pathologic examination. The type of neoplasia most frequently described in Literature is that of the papillary carcinoma (82%). Other types of carcinomas are also reported in Literature: mixed follicular-papillary carcinomas (9 cases), squamous cell carcinomas (10 cases) and follicular carcinomas (3 cases). There are different theories regarding the origin of and therapy for these malignancies. In the sixties some Authors thought that these carcinomas were metastases of thyroid carcinomas. Now, following demonstration of normal thyroid tissue occurrence in the wall of thyroglossal duct cysts, it is almost universally accepted that a carcinoma may arise from thyroglossal remnants. The foci of cancer found in the thyroid reported only infrequently in Literature are a result of the plurifocality of papillary carcinoma. The Authors suggest that the Sistrunk procedure is an adequate, sufficient treatment if the carcinoma is limited to the cyst's walls. They also recommend postoperative administration of substitution therapy of thyroid hormones. Indications for thyroidectomy are then discussed.