18F]fluoroethoxy-benzovesamicol, a PET radiotracer for the vesicular acetylcholine transporter and cholinergic synapses

CACO-2 BBE was used to determine the response of a gastrointestinal epithelium to tumor necrosis factor-alpha (TNF). Incubation of CACO-2 BBE with TNF did not produce any effect on transepithelial resistance (TER) within the first 6 hr but resulted in a 40-50% reduction in TER and a 30% decrease in 1SC (short circuit current) relative to time-matched control at 24 hr. The decrease in TER was sustained up to 1 week following treatment with TNF and was not associated with a significant increase in the transepithelial flux of [14C]-D-mannitol or the penetration of ruthenium red into the lateral intercellular space. Dilution potential and transepithelial 22Na+ flux studies demonstrated that TNF-treatment of CACO-2 BBE cell sheets increased the paracellular permeability of the epithelium to Na+ and Cl-. The increased transepithelial permeability did not associate with an increase in the incidence of apoptosis. However, there was a TNF-dependent increase in [3H]-thymidine labeling that was not accompanied by a change in DNA content of the cell sheet. The increase in transepithelial permeability was concluded to be across the tight junction because: (i) 1 mM apical amiloride reduced the basolateral to apical flux of 22Na+, and (ii) dilution potential studies revealed a bidirectionally increased permeability to both Na+ and Cl-. These data suggest that the increase in transepithelial permeability across TNF-treated CACO-2 BBE cell sheets arises from an alteration in the charge selectivity of the paracellular conductive pathway that is not accompanied by a change in its size selectivity.     

The herpesvirus protease: mechanistic studies and discovery of inhibitors of the human cytomegalovirus protease

This paper is a review of the literature on the possible association between osteoporosis and oral bone loss, with an emphasis on radiological studies. Such an association was first suggested in 1960. Subsequent histomorphometric and microradiographic studies showed that after the age of 50 there was a marked increase in the cortical porosity of the mandible, with this increase being greater in the alveolar bone than the mandibular body; and that with this increase in porosity, there was a concomitant decrease in bone mass, which appeared to be more pronounced in females than in males, with the loss in bone mineral content estimated to be 1.5% per year in females and 0.9% in males. These studies also demonstrated a considerable amount of variation in the amounts of cortical and trabecular bone within and among individuals. Subsequent clinical studies reported associations between the bone densities of jaws and (1) metacarpals, (2) forearm bones, (3) vertebrae and (4) femurs. These studies indicated that women had lower mandibular bone mineral content (BMC) than men and that age-related loss of bone was more pronounced in women after the age of 50 years than in men of the same age, as was the case for the rest of the body. It was suggested that systemic factors responsible for osteoporotic bone loss may combine with local factors (periodontal diseases) to increase rates of periodontal alveolar bone loss. Although not all studies found associations between osteoporosis and oral bone loss, the conclusion of this review is that such an association exists; yet additional longitudinal investigations are needed to confirm this, and before the implications of this association could be fully utilized in clinical dentistry, inexpensive methods must be developed for sensitive and specific measures of oral bone loss.     

Psychological states in terminal cancer patients as measured over time.

Examined the level of and the change over time in denial, death anxiety, anxiety, depression, hostility, love, being, and self-esteem in terminal cancer patients. Ss were 30 cancer patients (aged 51–74 yrs), 27 arthritic patients (aged 52–75 yrs) who constituted a chronically ill, but not terminal, control group, and 30 healthy control Ss (aged 51–76 yrs). Psychometric instruments to assess the psychological states (the Multiple Affect Adjective Check List, the Rosenberg Self-Esteem Scale, the Death Anxiety Scale, and the Being and Love scales of the Personal Orientation Inventory) were administered 3 times at 6-wk intervals. The cancer patients had significantly lower death anxiety than the control Ss, and a relative increase in the Being variable over time. There was little evidence of appreciable denial of serious illness in the cancer patients and an inverse relation between death anxiety and denial, which lends some support to clinical opinions that denial protects against death anxiety. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alpha-helical, but not beta-sheet, propensity of proline is determined by peptide environment

Proline is established as a potent breaker of both alpha-helical and beta-sheet structures in soluble (globular) proteins. Thus, the frequent occurrence of the Pro residue in the putative transmembrane helices of integral membrane proteins, particularly transport proteins, presents a structural dilemma. We propose that this phenomenon results from the fact that the structural propensity of a given amino acid may be altered to conform to changes imposed by molecular environment. To test this hypothesis on proline, we synthesized model peptides of generic sequence H2N-(Ser-LyS)2-Ala- Leu-Z-Ala-Leu-Z-Trp-Ala-Leu-Z-(Lys-Ser)3-OH (Z = Ala and/or Pro). Peptide conformations were analyzed by circular dichroism spectroscopy in aqueous buffer, SDS, lysophosphatidylglycerol micelles, and organic solvents (methanol, trifluoroethanol, and 2-propanol). The helical propensity of Pro was found to be greatly enhanced in the membrane-mimetic environments of both lipid micelles and organic solvents. Proline was found to stabilize the alpha-helical conformation relative to Ala at elevated temperatures in 2-propanol, an observation that argues against the doctrine that Pro is the most potent alpha-helix breaker as established in aqueous media. Parallel studies in deoxycholate micelles of the temperature-induced conformational transitions of the single-spanning membrane bacteriophage IKe major coat protein, in which the Pro-containing wild type was compared with Pro30 --> Ala mutant, Pro was found to protect the helix, but disrupt the beta-sheet structure as effectively as it does to model peptides in water. The intrinsic capacity of Pro to disrupt beta-sheets was further reflected in a survey of porins where Pro was found to be selectively excluded from the core of membrane-spanning beta-sheet barrels. The overall data provide a rationale for predicting and understanding the structural consequences when Pro occurs in the context of a membrane.     

Epidermal growth factor receptor and its inhibition in radiotherapy: in vivo findings

Increasing evidence shows that dysregulated epidermal growth factor receptor (EGFR) signalling plays an important part in neoplasia. When over expressed or mutated, EGFR is frequently associated with more aggressive tumour growth, poor patient prognosis and resistance of tumours to cytotoxic agents, including radiation. The present studies with murine carcinomas showed that there is an inverse correlation between the level of EGFR and tumour radiocurability. Likewise, the present clinical study in patients with head and neck cancer shows that EGFR over expression correlates with poorer tumour response to radiotherapy. Adding EGFR to tumour cells in vitro protected cells against the cytotoxic action of radiation, whereas blocking EGFR with anti-EGFR antibodies enhanced cell radiosensitivity. A casual relationship between EGFR and increased cellular resistance to radiation was established by transferring the EGFR gene into low EGFR-expressing radiosensitive tumour cells, which then become radioresistant. Radiation activated EGFR and its downstream signalling pathways in radioresistant but not in radiosensitive tumours, and this effect was associated with increased resistance to radiation, and enhanced repopulation in irradiated tumours. Increasing evidence shows that blockage of EGFR or interference with any of the steps in its signal transduction cascade can counteract negative outcomes of EGFR signalling, which has recently been explored as a therapeutic strategy in cancer treatment. The present findings demonstrate that treatment of human tumour xenografts with C225, an anti-EGFR monoclonal antibody, dramatically enhanced tumour response to radiation. Overall, the findings show that over expression of EGFR may serve as a predictor of tumour treatment outcome by radiotherapy and as a therapeutic target to enhance the efficacy of radiotherapy.     

The yeast SEN1 gene is required for the processing of diverse RNA classes

A single base change in the helicase superfamily 1 domain of the yeast Saccharomyces cerevisiae SEN1 gene results in a heat-sensitive mutation that alters the cellular abundance of many RNA species. We compared the relative amounts of RNAs between cells that are wild-type and mutant after temperature-shift. In the mutant several RNAs were found to either decrease or increase in abundance. The affected RNAs include tRNAs, rRNAs and small nuclear and nucleolar RNAs. Many of the affected RNAs have been positively identified and include end-matured precursor tRNAs and the small nuclear and nucleolar RNAs U5 and snR40 and snR45. Several small nucleolar RNAs co-immunoprecipitate with Sen1 but differentially associate with the wild-type and mutant protein. Its inactivation also impairs precursor rRNA maturation, resulting in increased accumulation of 35S and 6S precursor rRNAs and reduced levels of 20S, 23S and 27S rRNA processing intermediates. Thus, Sen1 is required for the biosynthesis of various functionally distinct classes of nuclear RNAs. We propose that Sen1 is an RNA helicase acting on a wide range of RNA classes. Its effects on the targeted RNAs in turn enable ribonuclease activity.     

Contrast of survey results between state and a cohort of nonstate mycobacteriology laboratories: changes in laboratory practices

Based on the recommendations of a 1992 conference on tuberculosis, the Centers for Disease Control and Prevention (CDC) established programs for upgrading mycobacteriology laboratories by providing them with monies and focused training. In 1991, state public health laboratories were surveyed to determine the methods they were using for primary Mycobacterium tuberculosis testing and their turnaround times for reporting testing results. A similar survey of nonstate laboratories participating in the National Laboratory Training Network-sponsored, M. tuberculosis-focused training programs was conducted from May 1992 to June 1993. In 1994, follow-up surveys of both the state- and nonstate-laboratory cohorts were conducted with the questionnaire from the initial survey plus additional questions that asked about interventions and changes occurring in the laboratory since the original survey. Although both cohorts showed increases in the percentages of laboratories meeting the recommended turnaround times for reporting M. tuberculosis testing results and using the recommended rapid methods for testing, generally, the increases made by the state laboratories were greater. By June 1994, all state laboratories were using a rapid method for M. tuberculosis isolate identification compared with 88% of the nonstate laboratories. The percentage of laboratories identifying isolates within the recommended 21 days also increased more in the group of state laboratories than in the group of nonstate laboratories (state laboratories, 22 to 73%; nonstate laboratories, 55 to 59%). Responses from the follow-up survey showed large differences in the percentages of laboratories that received CDC funding (state laboratories, 100%; nonstate laboratories, 6%) and participated in M. tuberculosis training (state laboratories, 98%; nonstate laboratories, 45%). These results indicate that adequate funding and focused training are critical in maintaining state-of-the-art mycobacteriology laboratories.     

EAST长时间数据采集及远程实时显示系统

为了适应EAST长脉冲放电的需要,有必要进行长时间数据采集,并将实验诊断信号进行远程实时显示,使实验人员在实验中及时了解装置的运行状态,从而做出判断和决策。文章用PCI-9112数据采集卡设计并实现了EAST实验诊断信号数据采集并实现了数据的远程实时显示,详细介绍了系统的硬件结构、软件设计和实现。     

Rats with area postrema lesions have lengthy eating and drinking bouts when fed ad libitum: implications for feedback inhibition of ingestive behavior

Ad libitum ingestive behavior of rats with area postrema lesions (APX) was monitored electronically every 6 s for 23 hr. Whereas control rats ate on average 32.2 g of food each day in 16.3 distinct bouts, rats with APX ate comparable amounts of food (28.6 g) in much fewer daily bouts (5.8) that were very large. Controls drank 38.4 ml of water daily in 17.8 bouts, whereas rats with APX consumed more than twice as much water (101.5 ml) in a similar number of bouts (18.5). Controls drank 5.3 ml of 0.5 M NaCl daily in 7.0 bouts, whereas rats with APX consumed 9 times as much saline (45.5 ml) in more bouts (18.2) that were relatively large. These and other results suggest that the area postrema plays an important role in detecting inhibitory signals generated by food or fluid intake and that feeding and drinking bouts may increase in size after APX, because the feedback inhibition provided by those signals is diminished.     

A comparative study of coherent bremsstrahlung and channeling radiation

Employing many-beam codes for transversely bound electrons moving through crystal lattices, we calculate channeling radiation (CR) and coherent bremsstrahlung (CB) intensities in the few and few-tens-of MeV region. CB is found to be of an intensity comparable to that of CR, and dominating the spectrum beyond the Lindhard angle in the form of well defined peaks.