Hepatic Kupffer cell blockade reduces mortality of acute hemorrhagic pancreatitis in mice

BACKGROUND: Recovery of upper aerodigestive tract function after reconstruction of segmental oromandiblectomy defects is frequently incomplete. The purpose of this study was to quantitate postreconstruction function and define variables that predict functional outcome in this population. METHODS: A prospective study of 21 patients who underwent microvascular free tissue transfer reconstruction of segmental oromandibular defects was performed. Measures of swallowing, speech, bite, and oral intake were performed preoperatively and at 1, 3, 6, and 12 months postoperatively or until plateau. Preoperative versus maximal postoperative measures were compared and correlated with nine potentially predictive variables. Univariate and multivariate analyses were performed to determine the most significant predictive factors. RESULTS: Baseline function in the study population was abnormal. Postoperative bite force improved, but swallowing, speech, and oral intake were worse than preoperative. Significant (univariate) predictors of outcome included diagnosis of cancer, tongue resection, pharynx resection, and flap skin paddle area. Only tongue resection remained significant in multivariate analysis. CONCLUSIONS: Increasing need for oropharyngeal lining replacement, especially after tongue resection, is the most important predictor of functional outcome in reconstruction of segmental mandible defects.     

The relation between morbidity and cognitive performance in a normal aging population

BACKGROUND: Factors related to physical health have been implicated in both normal and pathological aging of cognitive abilities. To substantiate this notion, we studied existing morbidity, as diagnosed by the general practitioner according to well-defined criteria, as a potential predictor of cognitive test performance. METHODS: A sample of 1360 individuals, aged 24-81 years and living in the community, was stratified for age, sex, and general ability. Active and total morbidity in this group were classified according to the International Classification of Primary Care. Neurocognitive tests were used to assess the domains of verbal memory, sensorimotor speed, and cognitive flexibility. RESULTS: Multiple regression analyses with adjustment for age, sex, and educational level showed both insulin-dependent and noninsulin-dependent diabetes to be negatively associated with all cognitive measures. More specific negative associations were found for chronic bronchitis (performance speed) and presbyacusia (memory). Single or aggregated cardiovascular morbidity (including hypertension) was unrelated to test performance. CONCLUSIONS: Existing morbidity as a whole contributes only modestly (up to 3.5%) to total variance in cognitive function. However, some specific, relatively common diseases of the elderly, such as diabetes and chronic bronchitis, may aggravate the age-related decline in cognitive ability.     

Novel developmentally regulated phosphoinositide binding proteins from soybean whose expression bypasses the requirement for an essential phosphatidylinositol transfer protein in yeast

Phosphatidylinositol transfer proteins (PITPs) have been shown to play important roles in regulating a number of signal transduction pathways that couple to vesicle trafficking reactions, phosphoinositide-driven receptor-mediated signaling cascades, and development. While yeast and metazoan PITPs have been analyzed in some detail, plant PITPs remain entirely uncharacterized. We report the identification and characterization of two soybean proteins, Ssh1p and Ssh2p, whose structural genes were recovered on the basis of their abilities to rescue the viability of PITP-deficient Saccharomyces cerevisiae strains. We demonstrate that, while both Ssh1p and Ssh2p share approximately 25% primary sequence identity with yeast PITP, these proteins exhibit biochemical properties that diverge from those of the known PITPs. Ssh1p and Ssh2p represent high-affinity phosphoinositide binding proteins that are distinguished from each other both on the basis of their phospholipid binding specificities and by their substantially non-overlapping patterns of expression in the soybean plant. Finally, we show that Ssh1p is phosphorylated in response to various environmental stress conditions, including hyperosmotic stress. We suggest that Ssh1p may function as one component of a stress response pathway that serves to protect the adult plant from osmotic insult.     

Polymorphic expression of the UDP-glucuronosyltransferase UGT1A gene locus in human gastric epithelium

OBJECTIVES: Adenosine, a potent coronary vasodilator is used as a pharmacologic stress agent for the assessment of coronary artery disease. A paucity of data exists on its effects on filling dynamics. Accordingly, this study was undertaken to evaluate the effects of adenosine on left ventricular filling as assessed by Doppler echocardiography. METHODS AND RESULTS: We studied 69 patients (45 men, 24 women, aged 61+/-11 years) referred for evaluation of coronary artery disease. Two-dimensional echocardiography and pulsed-Doppler recordings at the mitral valve tips and annulus were performed at baseline and at maximal adenosine infusion of 140 microg/kg/min. During adenosine infusion, an increase in heart rate occurred (70+/-14 beats/min to 85+/-16 beats/min), with a mild decrease in blood pressure (130/75+/-26/13 mm Hg vs 119/66+/-25/13 mm Hg); both p < 0.02. Changes in filling dynamics included an increase in peak early inflow velocity, E/A ratio, and normalized peak filling rate. Of the patients investigated, 23 had one-vessel coronary artery disease, 29 had coronary disease in two vessels or more by angiography, and 17 had no significant disease. Patients without coronary artery disease (controls) had mild changes in E/A ratio (mean 7%). Patients with coronary artery disease had a more heterogeneous change in filling dynamics (range 43% to 369%, mean 26%), with a significant overlap with controls. However, changes in E/A ratio during adenosine infusion that exceeded the confidence limits of normal (-20% to +30%) were specific for coronary artery disease, with a positive predictive value of 84%. CONCLUSIONS: Normally, adenosine induces significant increases in early filling as assessed by Doppler. The changes in patients with coronary stenosis are more variable. When these changes fall outside the confidence limits of normal, they are predictive of coronary artery disease.     

Unilateral cricothyroid contraction and glottic configuration

The outpatient population using the emergency department (ED) is increasing and so is the risk of not admitting people who need it. There is, thus, one important question: are the services delivered appropriate to the needs of these ED outpatients? Follow-up of non-admitted patients after a visit to the ED is a prerequisite for the evaluation of these health services. A multicentric follow-up study was thus performed in order to assess the possibility of contacting outpatients after a visit to the ED. Three randomized follow-up methods were compared: (1) telephone call 1 week after the emergency department visit; (2) telephone call 2 weeks after the visit; (3) telephone call 4 weeks after the visit. The follow-up rate did not change depending on whether patients were contacted at 1, 2 or 4 weeks after the visit. The success rate was 78.6%, 85.6% and 74% respectively (NS). In each strategy, 50% of patients were contacted at the first telephone call, 20% at the second telephone call and 10% by mail. Thus, in a group of outpatients who gave their consent to be called, the follow-up was found to be feasible with a high success rate whatever the time between the visit and the phone recall.     

Thrombospondin-1 and its CSVTCG-specific receptor in wound healing and cancer

Accumulation of mutant p53 protein occurs frequently in human malignancies, including 40-60% of non-small cell lung carcinomas. The implications of such p53 over-expression, usually assessed by immunohistochemical techniques, for the prognosis of lung cancer patients remain undetermined. In this study, we used a time-resolved immunofluorometric assay to measure p53 protein concentrations in extracts prepared from 86 primary non-small cell lung tumours and examined the associations between p53 protein levels (corrected for total protein) and other clinico-pathologic variables, including post-surgical disease-free and overall survival. Contingency tables analysed by chi2 tests revealed no significant relationships between p53 status, defined by a median cut-off point, and patient gender, age, disease stage, histologic grade and type, lymph node extension, smoking history and administration of adjuvant chemotherapy or radiation. However, multivariate Cox proportional hazard regression analysis demonstrated a dose-response relationship between p53 concentration, expressed as a 4-level, quartile-divided variable, and increased risk of relapse (p = 0.010) and death (p = 0.016). Patients whose tumours contained p53 concentrations exceeding the median value had over 3-fold higher risk of relapse (p = 0.002) and death (p = 0.007) than those whose tumours had lower p53 concentrations. We also provide evidence suggesting that the impact of p53 on survival is greater in patients with squamous cell carcinoma than in those with adenocarcinoma. Although the latter finding needs confirmation, our results suggest that application of an immunoassay of p53 protein on non-small cell lung tumour extracts may identify patients at increased risk of unfavourable outcome.     

Time-dependent changes of inflammatory mediators in the lungs of humans exposed to 0.4 ppm ozone for 2 hr: a comparison of mediators found in bronchoalveolar lavage fluid 1 and 18 hr after exposure

Acute exposure of humans to ozone results in reversible respiratory function decrements and cellular and biochemical changes leading to the production of substances which can mediate inflammation and acute lung injury. While pulmonary function decrements occur almost immediately after ozone exposure, it is not known how quickly the cellular and biochemical changes indicative of inflammation occur in humans. Increased bronchoalveolar lavage (BAL) fluid levels of neutrophils (PMNs) and prostaglandins (PGE2) have been reported in humans as early as 3 hr and as late as 18 hr after exposure. The purpose of this study was to determine whether a broad range of inflammatory mediators are elevated in BAl fluid within 1 hr of exposure. We exposed eight healthy volunteers twice: once to 0.4 ppm ozone and once to filtered air. Each exposure lasted for 2 hr during which the subjects underwent intermittent heavy exercise (66 liters/min). BAL was performed 1 hr after the exposure. Ozone induced rapid increases in PMNs, total protein, LDH, alpha-1 antitrypsin, fibronectin, PGE2, thromboxane B2, C3a, tissue factor, and clotting factor VII. In addition, there was a decrease in the recovery of total cells and alveolar macrophages, and decreased ability of alveolar macrophages to phagocytize Candida albicans. A comparison of these changes with changes observed in an earlier study in which subjects underwent BAL 18 hr after an identical exposure regimen indicates that IL-6 and PGE2 levels were higher 1 hr after exposure than 18 hr after exposure, fibronectin and tissue-plasminogen activator levels were higher 18 hr after exposure, and that PMNs, protein, and C3a were present at essentially the same levels at both times. These results indicate that (i) several inflammatory mediators are already elevated 1 hr after exposure; (ii) some mediators achieve their maximal levels in BAL fluid at different times following exposure. These data suggest that the inflammatory response is complex, depending on a cascade of timed events, and that depending on the mediator of interest one must choose an appropriate sampling time.     

Solution structure of an oligodeoxynucleotide containing the human N-ras codon 12 sequence refined from 1H NMR using molecular dynamics restrained by nuclear Overhauser effects

A general model is developed for segmenting magnetic resonance images using vector decomposition and probability techniques. Each voxel is assigned fractional volumes of q tissues from p differently weighted images (q < or = p + 1) in the presence of partial-volume mixing, random noise, and other tissues. Compared with the eigenimage method, fewer differently weighted images are needed for segmenting the q tissues, and the contrast-to-noise ratio in the calculated fractional volumes is improved. The model can produce composite tissue-type images similar to that of the probability methods, by comparing the fractional volumes assigned to different tissues on each voxel. A three-tissue (p = 2, q = 3) model is illustrated for segmenting three tissues from dual-echo images. It provides statistical analysis to the algebraic method. A three-compartment phantom is segmented for validation. Two clinical examples are presented.     

Application of wavelet compression to digitized radiographs

Capillary electrophoresis is applied to determine nucleotide pool levels in human Burkitt lymphoma cells. The analysis was performed on a 65 cm x 50 microns I.D. Ucon-coated column with on-column UV detector. The method requires only nanoliters of sample and a simple sample preparation procedure. Over 12 nucleotides were separated and quantitated with high resolution and reproducibility. The whole capillary electrophoretic separation time was only 35 min. These results demonstrate that capillary electrophoresis provides a useful and easy way to analyze nucleotide pools in cells.