Effect of aspirin on prostaglandin E2 and leukotriene B4 production in human colonic mucosa from cancer patients

Elderly persons typically show diminished immune responsiveness to influenza vaccination. Chiron Vaccines has developed a novel oil-in-water adjuvant emulsion, MF59, to enhance vaccine immunogenicity without compromising safety and tolerability. MF59 was shown to augment influenza vaccine immunogenicity in senescent mice. Subsequently, eight similarly designed, randomized, controlled clinical trials of a subunit influenza vaccine combined with MF59 were conducted between 1992 and 1995 in 1807 elderly volunteers (> or = 65 years old). Mild, transient, injection-site reactions were increased with MF59, but systemic reactions generally were not. For two of the three vaccine antigens (B and A/H3N2), postimmunization haemagglutinin inhibition geometric mean titres were statistically significantly higher with MF59. During influenza season, fewer deaths occurred among MF59 recipients. This development programme demonstrates how an adjuvant that stimulates effectors associated with immunosenescence can improve the performance of an existing vaccine in elderly persons.     

Alcohol intake of P rats is regulated by muscarinic receptors in the pedunculopontine nucleus and VTA

The CtpA protein in the cyanobacterium Synechocystis 6803 is a C-terminal processing protease that is essential for the assembly of the manganese cluster of the photosystem II complex. When fused to different chloroplast-targeting transit peptides, CtpA can be imported into isolated spinach chloroplasts and is subsequently translocated into the thylakoid lumen. Thylakoid transport is mediated by the cyanobacterial signal peptide which demonstrates that the protein transport machinery in thylakoid membranes is functionally conserved between chloroplasts and cyanobacteria. Transport of CtpA across spinach thylakoid membranes is affected by both nigericin and sodium azide indicating that the SecA protein and a transthylakoidal proton gradient are involved in this process. Saturation of the Sec-dependent thylakoid transport route by high concentrations of the precursor of the 33-kDa subunit of the oxygen-evolving system leads to a strongly reduced rate of thylakoid translocation of CtpA which demonstrates transport by the Sec pathway. However, thylakoid transport of CtpA is affected also by excess amounts of the 23-kDa subunit of the oxygen-evolving system, though to a lesser extent. This suggests that the cyanobacterial protein is capable of also interacing with components of the deltapH-dependent route and that transport of a protein across the thylakoid membrane may not always be restricted to a single pathway.     

Effect on production traits of bovine somatotropin for up to three consecutive lactations.

Thirteen (control) cows were injected daily with saline and 22 with bST (12 at 10.3 mg/d and 10 at 20.6 mg/d) through wk 5 to 42 of lactation. Nine of the treated cows had received bST in the previous lactation, and 7 cows received bST in the previous two lactations. All control cows and 6 treated cows had not previously received bST. Treatment with bST caused substantial increases in milk production, feed intake, and efficiency of feed conversion in the current lactation, which is consistent with previous trials. Increases in feed intake were established fully within 9 wk of starting bST administration, somewhat earlier than usually reported. Treatment with bST in one or two previous lactations caused a statistically significant 14% reduction in production and 8% reduction in efficiency of feed conversion during the first 9 wk of bST treatment in the current lactation; reductions observed later in lactation were not statistically significant. Differences for other traits were not statistically significant. In combination with earlier trials, these results suggest that, although bST has beneficial effects on production and efficiency traits, these benefits may be considerably lower in the second and subsequent lactations of bST use. However, carry-over effects on cows not receiving bST in the current lactation were not explored in this trial.     

Application of a mechanistic model of bovine milk protein synthesis to examine the use of isotope labeling methods

Two types of models of bovine milk protein synthesis were used to simulate collection and analysis of data from infusion experiments involving isotope-labeled amino acids (AA). Analytical solutions to a system of ordinary differential equations that describe isotope enrichment curves of each AA pool within the mammary gland were derived and are presented. Numerical solutions from a dynamic mechanistic model suggest that normal experimental procedures can affect the shape of enrichment curves and, therefore, results derived from them. Simulation results suggest that standard methods utilizing in vivo isotope kinetics may be of limited value to characterize the metabolism of the bovine mammary gland, especially AA metabolism and milk protein synthesis and secretion. The results clearly demonstrate the flexibility of such models for the testing of many hypotheses and possible experimental protocols.     

Effects of clozapine on use of seclusion and restraint at a state hospital

We report on an 8-year-old boy with a pattern of multiple congenital anomalies that strongly suggest DK-phocomelia syndrome. Birth findings included bilateral upper limb amelia, occipital encephalocele, agenesis of the corpus callosum, right auricular tag, scoliosis, small penis, and cryptorchidism. Dental malocclusion was observed in the follow-up. This is the first case with on 8-year follow-up report of DK-phocomelia syndrome.     

Hyperhomocysteinemia and atherosclerotic vascular disease: pathophysiology, screening, and treatment. off

Hyperhomocysteinemia has recently been identified as an important risk factor for atherosclerotic vascular disease. This article reviews homocysteine metabolism, causes of hyperhomocysteinemia, the pathophysiological findings of this disorder, and epidemiological studies of homocysteine and vascular disease. Screening for hyperhomocysteinemia should be considered for patients at high risk for vascular disease or abnormalities of homocysteine metabolism. For primary prevention of vascular disease, treatment of patients with homocysteine levels of 14 micromol/L or higher should be considered. For secondary prevention, treatment of patients with homocysteine levels of 11 micromol/L or higher should be considered. Treatment is most conveniently administered as a folic acid supplement (400-1000 microg) and a high-potency multivitamin that contains at least 400 microg of folate. Higher doses of folic acid and cyanocobalamin supplements may be required in some patients. Until prospective clinical trial data become available, these conservative recommendations provide a safe, effective, and evidence-based approach to the diagnosis, evaluation, and management of patients with hyperhomocysteinemia.     

Prophylactic antibiotics in surgery for chronic ear disease

OBJECTIVES/HYPOTHESIS: The role of prophylactic antibiotics in otologic surgery continues to be debated and perhaps misused. Prior studies have provided conflicting evidence with regard to the benefit obtained from the use of prophylactic antibiotics in surgery for chronic otitis media. The current study was designed to evaluate the role of prophylactic antibiotics in the outcomes of surgery for chronic ear disease. It was the authors' impression that there was no indication for prophylactic antibiotics in such surgery. STUDY DESIGN: Randomized prospective study performed in a tertiary care facility. METHODS: Patients who met inclusion criteria (n = 146) were randomly assigned to an antibiotic treatment group or a control group receiving no prophylactic antibiotics. Patients in the antibiotic treatment group were given preoperative intravenous antibiotics followed by oral antibiotics for 5 days after surgery. Patients were followed postoperatively and observed for clinical evidence of infection and graft failure. RESULTS: There was no statistically significant difference between the two groups with regard to the incidence of postoperative infection or graft survival. CONCLUSIONS: The use of prophylactic antibiotics in surgery for chronic ear disease cannot be recommended based on the findings of this study.     

Fine mapping of the locus for nevoid basal cell carcinoma syndrome on chromosome 9q

The nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized primarily by multiple basal cell carcinomas, odontogenic keratocysts, and pits of the palms and soles. Tumor deletion studies and linkage analysis in Caucasians have revealed that the gene is on chromosome 9q. To further refine the location of the nevoid basal cell carcinoma syndrome locus, we tested linkage to this region in three families. Evaluation of recombinants suggested that the nevoid basal cell carcinoma syndrome locus lies in the interval defined distally by D9S127. Our data, together with existing published data defining D9S12 as a proximal flanking marker, refine the location of nevoid basal cell carcinoma syndrome to an 8.3-cM interval. Two of the families studied were African-American and show a notable variation in phenotypic expression in which affected individuals developed few skin cancers. However, despite clinical heterogeneity, our data are consistent with the hypothesis that the same locus is involved in these African-American families.     

Inositol 1,4,5-trisphosphate [correction of tris-phosphate] activation of inositol trisphosphate [correction of tris-phosphate] receptor Ca2+ channel by ligand tuning of Ca2+ inhibition

Inositol 1,4,5-trisphosphate (IP3) [corrected] binding to its receptors (IP3R) in the endoplasmic reticulum (ER) activates Ca2+ release from the ER lumen to the cytoplasm, generating complex cytoplasmic Ca2+ concentration signals including temporal oscillations and propagating waves. IP3-mediated Ca2+ release is also controlled by cytoplasmic Ca2+ concentration with both positive and negative feedback. Single-channel properties of the IP3R in its native ER membrane were investigated by patch clamp electrophysiology of isolated Xenopus oocyte nuclei to determine the dependencies of IP3R on cytoplasmic Ca2+ and IP3 concentrations under rigorously defined conditions. Instead of the expected narrow bell-shaped cytoplasmic free Ca2+ concentration ([Ca2+]i) response centered at approximately 300 nM-1 microM, the open probability remained elevated (approximately 0.8) in the presence of saturating levels (10 microM) of IP3, even as [Ca2+]i was raised to high concentrations, displaying two distinct types of functional Ca2+ binding sites: activating sites with half-maximal activating [Ca2+]i (Kact) of 210 nM and Hill coefficient (Hact) approximately 2; and inhibitory sites with half-maximal inhibitory [Ca2+]i (Kinh) of 54 microM and Hill coefficient (Hinh) approximately 4. Lowering IP3 concentration was without effect on Ca2+ activation parameters or Hinh, but decreased Kinh with a functional half-maximal activating IP3 concentration (KIP3) of 50 nM and Hill coefficient (HIP3) of 4 for IP3. These results demonstrate that Ca2+ is a true receptor agonist, whereas the sole function of IP3 is to relieve Ca2+ inhibition of IP3R. Allosteric tuning of Ca2+ inhibition by IP3 enables the individual IP3R Ca2+ channel to respond in a graded fashion, which has implications for localized and global cytoplasmic Ca2+ concentration signaling and quantal Ca2+ release.