Identification of amino acid residues and protein kinases involved in the regulation of NFATc subcellular localization.

The subcellular localization of the transcription factor NFATc is tightly regulated by the calcium-regulated phosphatase calcineurin, which acts to directly dephosphorylate NFATc, causing its rapid translocation from the cytoplasm to the nucleus. The calcineurin-mediated nuclear localization of NFATc is opposed by poorly defined protein kinases that act either to directly antagonize nuclear import or, alternatively, to promote nuclear export. Here, we provide evidence that the cellular protein kinases JNK, ERK, p38, and CK2 (formerly casein kinase II) are involved in the regulation of NFATc subcellular localization. We show that JNK, ERK, and p38 physically associate with the NFATc N-terminal regulatory domain and can directly phosphorylate functionally important residues involved in regulating NFATc subcellular localization, namely Ser(172) and the conserved NFATc Ser-Pro repeats. Moreover, we found that overexpression of JNK, ERK, or p38 is able to block ionomycin-induced NFATc nuclear translocation, whereas treatment of cells with both PD98059 and SB202190, which inhibit MAPK/SAPK signaling pathways, is sufficient to trigger NFATc nuclear localization. Finally, we show that CK2 also binds the N terminus of NFATc and phosphorylates functionally important amino acid residues, including a conserved amino acid motif located downstream of each of the NFATc Ser-Pro repeats that appears to be important for regulating NFATc nuclear export. Collectively, these studies identify functionally important amino acid residues and protein kinases involved in the regulation of NFATc subcellular localization.

Screening and managing abdominal aortic aneurysms at the Ochsner Clinic: suggested algorithm and method of derivation. Department of Surgery and Ochsner Clinic Quality Assurance Committee.

An algorithm for screening and management of abdominal aortic aneurysms was developed at the Ochsner Medical Institutions to address the considerable variation identified in clinical practice. A consensus panel of physicians whose opinions differed regarding the management of abdominal aortic aneurysms was convened to develop the algorithm. Based on a literature review and clinical experience, the panel established criteria to determine how frequently and by which methodologies patients with abdominal aortic aneurysms should be followed and when a referral to a vascular surgeon is appropriate. The algorithm developed by the consensus panel method was used to establish practice guidelines that are flexible enough to address individual patient needs yet structured enough to eliminate inappropriate care. Data are being collected and analyzed in real time to determine whether elements of the algorithm should be revised.

Influenza B virus reinfection.

Four outbreaks of influenza B infection occurred in Houston, Texas in the years 1976-1984. In the Houston Family Study, age-related infection and illness rates in the recent two epidemics resembled those reported previously. A total of 118 persons, including 35 children followed from birth, were followed longitudinally through this entire period and 331 persons were studied through at least two outbreaks. Fifty-nine (88%) of 67 children studied for four outbreaks were infected and 25% had a second infection; about half of the adults had one infection but only one of 51 was reinfected. Infection rates were proportionally lower for those followed through 2-3 outbreaks. Those with documented infection were protected decreasingly over time against reinfection and associated illness in subsequent epidemics. Such protection decreased in efficacy from 65% after 2-3 years, to 46% after 4-5 years, and to no protection after seven years.