Brain regions supporting intentional and incidental memory: a PET study

Regional brain activity associated with intentional and incidental memory retrieval was studied with PET. Previously studied and new words were presented in either an intentional or an incidental memory task. Type of task was crossed with an encoding manipulation ('deep' vs 'shallow') which varied the probability that studied items would be remembered. In both tasks, deeply encoded items were associated with greater activation in the left hippocampus than were items that had received shallow encoding, suggesting that the involvement of the hippocampus in memory retrieval is independent of whether remembering is intentional or incidental. Right prefrontal and bilateral parietal cortex were more activated during the international task than during the incidental task, irrespective of encoding condition. Thus, these regions play a more extensive role in memory retrieval when remembering is intentional.     

The normal anterior commissure of the glottis

OBJECTIVE: We characterized the normal width of the anterior commissure of the glottis by measuring its dimensions on CT scans obtained in patients who had no laryngeal disorders. SUBJECTS AND METHODS: CT scans of patients referred for cervical CT myelography were prospectively reviewed by a single board-certified radiologist. Axial images through the anterior commissure (localized by vocal process of the arytenoid cartilage, the vocal muscle, or both) were magnified on the viewing console of the CT scanner. Window and level were chosen to simulate our routine settings for CT scans of the neck. Anteroposterior width of the anterior commissure was measured using an electronic ruler with 1-mm marks. RESULTS: Sixty-five patients were prospectively evaluated. Nine patients were excluded because of substantial motion artifact, and another 18 were excluded because CT images did not include the entire larynx. Thus, the final study group included 38 patients. The average width of the anterior commissure was 1.02 +/- 0.56 mm. The width was less than or equal to 1.1 mm in 22 (58%) of 38 patients. The width was less than or equal to 1.7 mm in 35 (92%) of 38 patients. Forty-two percent (16 of 38 patients) had anterior commissures wider than 1.0 mm. The maximum width of 2.2 mm was seen in only one patient. CONCLUSION: The mean width of the anterior commissure was approximately 1.0 mm. However, 42% of patients had anterior commissures wider than 1.0 mm. In our series, using an upper limit of 1.6 mm as a normal measurement for the anterior commissure would have included 92% of patients, and an upper limit of 2.1 mm would have encompassed the mean plus two SDs.     

MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein family

BACKGROUND: The fragile histidine triad (FHIT) protein is a member of the large and ubiquitous histidine triad (HIT) family of proteins. It is expressed from a gene located at a fragile site on human chromosome 3, which is commonly disrupted in association with certain cancers. On the basis of the genetic evidence, it has been postulated that the FHIT protein may function as a tumor suppressor, implying a role for the FHIT protein in carcinogenesis. The FHIT protein has dinucleoside polyphosphate hydrolase activity in vitro, thus suggesting that its role in vivo may involve the hydrolysis of a phosphoanhydride bond. The structural analysis of FHIT will identify critical residues involved in substrate binding and catalysis, and will provide insights into the in vivo function of HIT proteins. RESULTS: The three-dimensional crystal structures of free and nucleoside complexed FHIT have been determined from multiwavelength anomalous diffraction (MAD) data, and they represent some of the first successful structures to be measured with undulator radiation at the Advanced Photon Source. The structures of FHIT reveal that this protein exists as an intimate homodimer, which is based on a core structure observed previously in another human HIT homolog, protein kinase C interacting protein (PKCI), but has distinctive elaborations at both the N and C termini. Conserved residues within the HIT family, which are involved in the interactions of the proteins with nucleoside and phosphate groups, appear to be relevant for the catalytic activity of this protein. CONCLUSIONS: The structure of FHIT, a divergent HIT protein family member, in complex with a nucleotide analog suggests a metal-independent catalytic mechanism for the HIT family of proteins. A structural comparison of FHIT with PKCI and galactose-1-phosphate uridylyltransferase (GaIT) reveals additional implications for the structural and functional evolution of the ubiquitous HIT family of proteins.     

Antimicrobial resistance: implications for the clinician

Antimicrobial resistance has become an issue of global proportion, and this dilemma has greatly affected the intensive care unit (ICU) setting. Increased antimicrobial use and other selective pressures have created an environment in the ICU that is a testing ground for survival of microorganisms. By various mechanisms, gram-positive cocci and gram-negative bacilli are becoming more resistant to our current armamentarium of antimicrobials. Strategies to improve the current situation of reduced microbial susceptibility include the following: continued and specific surveillance in ICUs, antimicrobial protocols, continued isolation precautions and appropriate handwashing, increased education at all levels, increased use of immunotherapies, better use of our current antimicrobial agents, and increased research in finding new and innovative antimicrobial agents while curtailing the marketing ploys that promote excessive and inappropriate use of these valuable medications.     

Insulin down-regulates the inducible nitric oxide synthase pathway: nitric oxide as cause and effect of diabetes?

Evidence in this paper indicates that insulin can down-regulate the inducible nitric oxide synthase (iNOS) pathway in vivo. The iNOS pathway is up-regulated in diabetes-prone rats and mice and is associated with an autoimmune process. However, the results presented here indicate that macrophage nitric oxide (NO) production and iNOS mRNA expression are also elevated in rats or mice made diabetic by streptozotocin injection in which there is no primary autoimmune component. Insulin administration reduces NO production in autoimmune-prone and streptozotocin-induced diabetic rodents. Finally, insulin decreases macrophage NO production in normal hosts. These results indicate that the autoimmune paradigm is inadequate to explain increased NO in diabetes. As a potential mechanism to explain insulin-mediated regulation of NO production, TGF-1 may be involved because 1) macrophages from diabetic mice produce less TGF-beta1 than macrophages from normal hosts; 2) the circulating TGF-beta1 level is lower in diabetic mice; and 3) insulin administration increases circulating TGF-beta1 in normal mice. Together, these results provide evidence that increased NO in diabetes is not only a cause but also an effect of beta-cell destruction and results in part from a heretofore unrecognized immunomodulatory activity of insulin.