Adenosine to inosine editing by ADAR2 requires formation of a ternary complex on the GluR-B R/G site

RNA editing by members of the ADAR (adenosine deaminase that acts on RNA) enzyme family involves hydrolytic deamination of adenosine to inosine within the context of a double-stranded pre-mRNA substrate. Editing of the human GluR-B transcript is catalyzed by, the enzyme ADAR2 at the Q/R and R/G sites. We have established a minimal RNA substrate for editing based on the RIG site and have characterized the interaction of ADAR2 with this RNA by gel shift, kinetic, and cross-linking analyses. Gel shift analysis revealed that two complexes are formed on the RNA as protein concentration is increased; the ADAR monomers can be crosslinked to one another in an RNA-dependent fashion. We performed a detailed kinetic study of the editing reaction; the data from this study are consistent with a reaction scheme in which formation of an ADAR2.RNA ternary complex is required for efficient RNA editing and in which formation of this complex is rate determining. These observations suggest that RNA adenosine deaminases function as homodimers on their RNA substrates and may partially explain regulation of RNA editing in these systems

Case Series of Mediastinal Masses: A Single Institutional Experience

INTRODUCTION : The mediastinum is an extremely important and complex part of the thorax because it contains a variety of important organs and anatomic structures. Many histologically different neoplasms and cysts that affect people of all ages arise from the multiple anatomic structures present in the mediastinum.Because this area is also the site of numerous lymph nodes, metastases secondary to lesions in other parts of the body are also frequently found. Both benign and malignant lesions are being recognized with increasing frequency, and a differential diagnosis is important whenever possible. The incidence and types of the many primary mediastinal tumors and cysts vary with the age of the patient group under consideration. In infants and children, neurogenic tumors are the most common, followed by lymphomas, foregut cysts, and benign germ cell tumors. In adults, thymic tumors are the most common surgically treated mediastinal tumors. Treatment strategies for mediastinal tumors and cysts are quite broad, depending on the nature of the disease. Major changes have recently occurred in the clinical presentation, diagnosis, and management of primary lesions of the mediastinum. New diagnostic techniques and improved therapy have led to more objective preoperative diagnoses as well as better longterm results. Mediastinal masses are the lesions in the thoracic space bounded superiorly by the thoracic inlet; inferiorly by the diaphragm , anteriorly by the sternum posteriorly by the spine, laterally bounded by the pleural spaces, including the mediastinal pleura. AIMS & OBJECTIVES : Retrospective nonrandomized observational study to review and analyze the experience in diagnosis and surgical management with emphasis on the evolution of surgical techniques at our institution in the treatment of Mediastinal Masses. MATERIALS AND METHODS : 71 consecutive patients diagnosed with mediastinal masses admitted in the Department of Cardiovascular and Thoracic surgery, Madras Medical College, Chennai, between September 2006 to April 2009 comprised the sample for this study. Case sheets of patients were obtained from Medical Record Department for analysis. A detailed clinical examination and findings were recorded over structured proforma for all patients. All patients under this study are classified according to their age, sex, mode of presentation, method of diagnosis, site of the tumour, surgical approach and postoperative morbidity, mortality work up. All patients were assessed and taken up for surgery. Under GA using double lumen ETT, patients were subjected for surgical procedure. Depending on the location and diagnosis, the necessary surgical procedure performed. Surgery was either incision biopsy, excision biopsy or debulking based on the tumor and sent for HPE. Post o perative b iopsy results were analysed compared and confirmed. Necessary patients were either referred to chemotherapy, radiotherapy or discharged home. SUMMARY & CONCLUSION : The mediastinum, an important compartment of the thoracic cavity, is the site for many cystic and tumoral lesions of various tissues. Since it contains various vital organs that could be compromised by such lesions, early diagnosis and appropriate treatment should be performed as soon as possible. However, the evaluation and treatment of mediastinal masses continue to present challenging problems to the surgeons. Recent advances in diagnostic techniques and the availability of multimodality y treatment r egimens subsequent t o surgery have enabled better therapeutic outcomes. Primary mediastinal tumors and cysts are common in young and middle aged patients. Most masses are discovered on routine radiographic examinations in asymptomatic patients, but many lesions produce non-specific clinical manifestations. Approximately two thirds of patients have symptoms at time of presentation. The absence of symptoms is a reasonably good indicator that the tumor may be of benign origin. Advances in imaging technology, radioisotopic improvement in cytology techniques and the introduction of radioimmunoassay, have enhanced the ability to assess more precisely the anatomic extent and the type of mediastinal mass. CT guided needle biopsy may be valuable in the verification of malignancy in about 80 to 90 % of cases. A proper evaluation should be done to determine the location and extension of the lesion. Since compression of the vital organs may be a significant risk, early diagnosis and proper surgical removal are mandatory . Mediastinoscopy may be necessary to make a diagnosis and respectability in this sense. Also novel approaches in anesthesia , surgical techniques, postoperative care, chemotherapy, immunotherapy and radioitherapy have improved mortality and morbidity, increasing survival and quality of life. On overview of this study revealed that out of the 71 cases studied, thymic tumors was diagnosed in18 cases, various cystic lesions in 8 cases, neurogenic lesions in 8 cases, tumors of germ cell origin form 8 cases, lymphomas in 4, esophageal and pleural lesions 2 in each. In this study postoperative morbidity were encountered in 5 cases. 1 case of peroperative mortality. Among the postoperative morbidity, 2 cases were reopened on the day of surgery for bleeding , 4 cases had postoperative wound dehiscence which were treated appropriately. 9 cases were referred for radiotherapy and chemotherapy for further management of the disease. Thymic tumor cases associated with myasthenia gravis (8) were treated preoperatively with 4 cycles of plasmapheresis followed by surgery and postoperatively by 4 cycles of plasmapheresis and tablet pyridostigmine was given. Patients were followed up in the neuro-medicine department. Overall analysis revealed benign mediastinal lesions in 59 and malignant in 8, specimen inconclusive in 8 cases. Among the benign lesions 51 cases had solid tumors while 8 patients had cystic lesions

A rare case of neomercazole induced hepatitis

Neomercazole is one of the most commonly used drugs to treat hyperthyroidism. Common side effects include rash, hair loss and agranulocytosis. Hepatotoxicity is a common side effect of Propylthiouracil, the other major antithyroid drug, but it has been rarely described as a side effect of neomercazole. Here, a patient presents with hepatitis 6 months after starting neomercazole therapy for graves disease. Diagnosis is based on excluding other causes of hepatitis, and treatment involves removing the offending drug. This is followed by normalization of liver function. Rechallenging should not be done as it can lead to recurrence of symptoms

Voltage-dependent behavior of a "ball-and-chain" gramicidin channel

This is the published version. Copyright 1997 by Elsevier.The channel-forming properties of two analogs of gramicidin, gramicidin-ethylenediamine (gram-EDA), and gramicidin-N,N-dimethylethylenediamine (gram-DMEDA) were studied in planar lipid bilayers, using protons as the permeant ion. These peptides have positively charged amino groups tethered to their C-terminal ends via a linker containing a carbamate group. Gram-DMEDA has two extra methyl groups attached to the terminal amino group, making it a bulkier derivative. The carbamate groups undergo thermal cis-trans isomerization on the 10–100-ms time scale. The conductance behavior of gram-EDA is found to be markedly voltage dependent, whereas the behavior of gram-DMEDA is not. In addition, voltage affects the cis-trans ratios of the carbamate groups of gram-EDA, but not those of gram-DMEDA. A model is proposed to account for these observations, in which voltage can promote the binding of the terminal amino group of gram-EDA to the pore in a "ball-and-chain" fashion. The bulkiness of the gram-DMEDA derivative prevents this binding