Cloned cDNA to cholecystokinin mRNA predicts an identical preprocholecystokinin in pig brain and gut.

Molecular cloning has established the structure of preprocholecystokinin in porcine cerebral cortex and duodenal mucosa. This precursor is 114 amino acids long, is identical in brain and gut, contains all the cholecystokinin (CCK) peptides previously isolated, and has the characteristics of a prohormone. It contains a putative amino-terminal signal peptide, basic processing sites, and a carboxyl-terminal amidation signal. The CCK mRNAs from brain and gut are approximately 850 nucleotides long and differ by only a few single base changes. This analysis establishes by a strict criterion that CCK is synthesized in both brain and gut and that the different distributions of molecular forms of CCK in the two tissues are most probably a consequence of tissue-specific posttranslational events.     

Report of the Task Force on Residency Training Information (2004-2005), American Board of Emergency Medicine

The American Board of Emergency Medicine gathers extensive background information on emergency medicine residency training programs and the residents training in those programs. We present the eighth annual report on the status of US emergency medicine residency programs.     

Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.     

On the role of macrophages in anthrax.

Bacillus anthracis, the causative agent of anthrax, produces systemic shock and death in susceptible animals, primarily through the action of its lethal toxin. This toxin, at high concentrations, induces lysis of macrophages in vitro but shows little or no effect on other cells. We found that when mice were specifically depleted of macrophages by silica injections, they became resistant to the toxin. Sensitivity could be restored by coinjection of toxin-sensitive cultured macrophages (RAW 264.7 cells) but not by coinjection of other cell lines tested. These results implied that macrophages mediate the action of lethal toxin in vivo and led us to investigate their role in death of the mammalian host. Sublytic concentrations of lethal toxin, orders of magnitude lower than those required to induce lysis of RAW 264.7 cells, were found to induce these cells to express interleukin 1 (IL-1) and tumor necrosis factor in vitro. Passive immunization against IL-1 or injection of an IL-1 receptor antagonist protected mice from toxin challenge, whereas anti-tumor necrosis factor provided little, if any, protection. These results imply that systemic shock and death from anthrax result primarily from the effects of high levels of cytokines, principally IL-1, produced by macrophages that have been stimulated by the anthrax lethal toxin.     

Structure of exotoxin A of Pseudomonas aeruginosa at 3.0-Angstrom resolution.

Exotoxin A of Pseudomonas aeruginosa is a secreted bacterial toxin capable of translocating a catalytic domain into mammalian cells and inhibiting protein synthesis by the ADP-ribosylation of cellular elongation factor 2. The protein is a single polypeptide chain of 613 amino acids. The x-ray crystallographic structure of exotoxin A, determined to 3.0-A resolution, shows the following: an amino-terminal domain, composed primarily of antiparallel beta-structure and comprising approximately half of the molecule; a middle domain composed of alpha-helices; and a carboxyl-terminal domain comprising approximately one-third of the molecule. The carboxyl-terminal domain is the ADP-ribosyltransferase of the toxin. The other two domains are presumably involved in cell receptor binding and membrane translocation.     

Synthesis of [11C]Bexarotene by Cu-Mediated [11C]Carbon Dioxide Fixation and Preliminary PET Imaging

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Caloric regulation and patterns of food choice in a patchy environment: the value and cost of alternative foods

Rats in a laboratory foraging paradigm had 24-hr-per-day access to a feeder where they could search, by completing a fixed number of bar presses, for an opportunity to eat one of a pair of foods differing in caloric density (2.5, 3, 3.5, or 4 kcal/g) and, in Experiment 2, the price of food pellets (10 to 50 bar presses per pellet). The rats could either accept the opportunity, and eat a meal, or reject it in favor of further search. Daily caloric intake was relatively constant. The rats always included both foods in their diet, but, for any particular food, the degree of inclusion in the diet and of acceptance of meal opportunities, the meal size, and the rate of eating were all functions not only of the price and caloric value of that food but also of the price and value of the alternately-available food. The patterns of intake for one food relative to those for the other available food were strongly correlated with the relative rate of calorie intake during consumption of that food compared to the other. Although the rats appeared to be sensitive to the local rates of calorie flow, they did not maximize daily calories consumed per time spent feeding.     

A framework for enhancing spatial and temporal granularity in report-based health surveillance systems

Background

Current public concern over the spread of infectious diseases has underscored the importance of health surveillance systems for the speedy detection of disease outbreaks. Several international report-based monitoring systems have been developed, including GPHIN, Argus, HealthMap, and BioCaster. A vital feature of these report-based systems is the geo-temporal encoding of outbreak-related textual data. Until now, automated systems have tended to use an ad-hoc strategy for processing geo-temporal information, normally involving the detection of locations that match pre-determined criteria, and the use of document publication dates as a proxy for disease event dates. Although these strategies appear to be effective enough for reporting events at the country and province levels, they may be less effective at discovering geo-temporal information at more detailed levels of granularity. In order to improve the capabilities of current Web-based health surveillance systems, we introduce the design for a novel scheme called spatiotemporal zoning.

Method

The proposed scheme classifies news articles into zones according to the spatiotemporal characteristics of their content. In order to study the reliability of the annotation scheme, we analyzed the inter-annotator agreements on a group of human annotators for over 1000 reported events. Qualitative and quantitative evaluation is made on the results including the kappa and percentage agreement.

Results

The reliability evaluation of our scheme yielded very promising inter-annotator agreement, more than a 0.9 kappa and a 0.9 percentage agreement for event type annotation and temporal attributes annotation, respectively, with a slight degradation for the spatial attribute. However, for events indicating an outbreak situation, the annotators usually had inter-annotator agreements with the lowest granularity location.

Conclusions

We developed and evaluated a novel spatiotemporal zoning annotation scheme. The results of the scheme evaluation indicate that our annotated corpus and the proposed annotation scheme are reliable and could be effectively used for developing an automatic system. Given the current advances in natural language processing techniques, including the availability of language resources and tools, we believe that a reliable automatic spatiotemporal zoning system can be achieved. In the next stage of this work, we plan to develop an automatic zoning system and evaluate its usability within an operational health surveillance system.