Characterization of the mIF4G Domains in the RNA Surveillance Protein Upf2p.

Thirty percent of all mutations causing human disease generate mRNAs with premature termination codons (PTCs). Recognition and degradation of these PTC-containing mRNAs is carried out by the mechanism known as nonsense-mediated mRNA decay (NMD). Upf2 is a scaffold protein known to be a central component of the NMD surveillance pathway. It harbors three middle domains of eukaryotic initiation factor 4G (mIF4G-1, mIF4G-2, mIF4G-3) in its N-terminal region that are potentially important in regulating the surveillance pathway. In this study, we defined regions within the mIF4G-1 and mIF4G-2 that are required for proper function of Upf2p in NMD and translation termination in Saccharomyces cerevisiae. In addition, we narrowed down the activity of these regions to an aspartic acid (D59) in mIF4G-1 that is important for NMD activity and translation termination accuracy. Taken together, these studies suggest that inherently charged residues within mIF4G-1 of Upf2p play a role in the regulation of the NMD surveillance mechanism in S. cerevisiae.

Interferon-alpha-induced sarcoidosis in a patient being treated for hepatitis C.

PATIENT: Female, 43 FINAL DIAGNOSIS: - SYMPTOMS: Diarrhea • generalized weakness • headache • lightheadedness • nausea • rash • short of breath • vomiting MEDICATION: - Clinical Procedure: - Specialty: Pulmonology. OBJECTIVE: Rare diseae. BACKGROUND: IFN-alpha-2b in combination with ribavirin is now the standard of care for the treatment of hepatitis C. Sarcoidosis is a chronic multisystem granulomatous disorder characterized by noncaseating granulomas in the involved organs. The pathologic hallmark of sarcoidosis is the presence of noncaseating granulomas in the interstitium that typically involve the lymphatics. CASE REPORT: A 43-year-old woman presented to our care with 2-week history of nausea, vomiting, diarrhea, shortness of breath, migraine headache, maculopapular rash, generalized weakness, and lightheadedness. She had been treated for hepatitis C with telaprevir, ribavirin, and interferon-alpha-2b for 6 months. Chest radiograph showed bilateral diffuse prominence of bronchovascular markings. CT of the chest revealed bilateral diffuse centrilobular nodules with associated intralobular septal thickening, thickening of the central peribronchovascular interstitium, nodularity of the major fissures, and mediastinal lymphadenopathy. These findings were suspicious for atypical pulmonary sarcoidosis, possibly interferon-induced. The pathology of the mediastinal lymph node biopsy revealed noncaseating granulomatous inflammation consistent with the diagnosis of pulmonary sarcoidosis. Pathology of the skin punch biopsy showed giant-cell granulomatous inflammation without necrosis. The patient was started on prednisone 40 mg daily with a steroid tapering course for 8 weeks. CONCLUSIONS: The management of IFN-induced sarcoidosis includes the discontinuation of IFN therapy with or without the administration of systemic corticosteroids. With the increasing prevalence of HCV in the United States, it is likely that more IFN-alpha-induced sarcoidosis will be encountered by clinicians.

Prevalence of steroid receptors and HER 2/neu in breast cancer biopsies of women living in Puerto Rico.

OBJECTIVE: The purpose of this study is to determine the prevalence rate of estrogen and progesterone receptors and HER 2/neu in the breast cancer biopsies analyzed in the Laboratory of Immunohistochemistry of the University of Puerto Rico School of Medicine in the year 2000. This data may serve as a reference point for future studies of the epidemiological aspects of breast cancer among women living in Puerto Rico. BACKGROUND: Determination of estrogen receptor (ER) and progesterone receptor (PR) on biopsy specimens of breast carcinoma prior to treatment is standard practice in the management of breast carcinoma. ER and PR are used to identify patients who are likely to respond to endocrine therapy. The prevalence of ER, PR and Her2/neu among USA women is 77%, 55% and 10-34%, respectively. One of the major clinical roles for testing HER 2/neu expression is to determine eligibility for treatment with Trastuzumab. METHODS: Retrospective analysis of 309 breast cancer biopsies was done. Paraffin embedded blocks of breast cancer tissue biopsies were received from different hospitals and Pathology Laboratories located throughout the island specifically for routine analysis of steroid receptor (ER/PR) and/or HER 2/neu expression. Immunostaining was performed in a Ventana Medical Systems automated instrument. RESULTS: Positive nuclear staining for ER and PR were seen in 65.9% (203/308) and 51.8% (159/307), respectively. In the HER2/neu test, 27.8% (46/165) gave a strong and complete membranous staining (score 3+). CONCLUSIONS: There is a lower prevalence of estrogen receptor in the breast cancer biopsies of women living in Puerto Rico than their USA counterparts, but similar prevalence of progesterone receptor status and HER 2/neu protein over expression.