Deletions in one domain of the Friend virus-encoded membrane glycoprotein overcome host range restrictions for erythroleukemia

Although the Friend virus-encoded membrane glycoprotein (gp55) activates erythropoietin receptors (EpoR) to cause erythroblastosis only in certain inbred strains of mice but not in other species, mutant viruses can overcome aspects of mouse resistance. Thus, mice homozygous for the resistance allele of the Fv-2 gene are unaffected by gp55 but are susceptible to mutant glycoproteins that have partial deletions in their ecotropic domains. These and other results have suggested that proteins coded for by polymorphic Fv-2 alleles might directly or indirectly interact with EpoR and that changes in gp55 can overcome this defense. A new viral mutant with an exceptionally large deletion in its ecotropic domain is now also shown to overcome Fv-2rr resistance. In all cases, the glycoproteins that activate EpoR are processed to cell surfaces as disulfide-bonded dimers. To initiate analysis of nonmurine resistances, we expressed human EpoR and mouse EpoR in the interleukin 3-dependent mouse cell line BaF3 and compared the abilities of Friend virus-encoded glycoproteins to convert these cells to growth factor independence. Human EpoR was activated in these cells by erythropoietin but was resistant to gp55. However, human EpoR was efficiently activated in these cells by the same viral mutants that overcome Fv-2rr resistance in mice. By construction and analysis of human-mouse EpoR chimeras, we obtained evidence that the cytosolic domain of human EpoR contributes to its resistance to gp55 and that this resistance is mediated by accessory cellular factors. Aspects of host resistance in both murine and nonmurine species are targeted specifically against the ecotropic domain of gp55.     

Nutrition support affects the distribution and organ uptake of cachectin/tumor necrosis factor in rats

BACKGROUND: We have previously observed a potentiation of the metabolic response to cachectin/tumor necrosis factor (TNF) by total parenteral nutrition (TPN) but not in anorexic orally fed animals. We hypothesized that nutritional status might affect TNF clearance kinetics. METHODS: We compared the clearance of a bolus of labeled TNF in TPN-fed animals given sufficient nutrients to grow called weight-gaining rats (WGR) with those given 50% of the WGR called weight-losing rats (WLR) and with orally fed rats (OFR). Data were analyzed using a two-compartment open system model and by linear systems analysis. RESULTS: The data from both types of analysis indicator that although metabolic clearance was similar, WGR had a slower fractional TNF clearance rate (FCR) as well as a larger volume of distribution than WLR or OFR. Further analysis showed that an increased proportion of the total mass of TNF resided in a plasma-associated compartment in WGR compared with WLR and OFR. In addition, WGR had reduced uptake of labeled TNF by the kidney. CONCLUSION: The data suggest that nutrition support influences either the distribution of TNF or the FCR, resulting in a greater retention in the plasma-associated compartment with intact absolute removal rates. This study has important implications concerning the type of nutrition support provided to the critically ill patient because our data suggest that clinical states with increased circulating TNF levels may be adversely affected by currently available nutritional practices.     

Preoperative pulmonary evaluation of the thoracic surgical patient

A test designed to separate those undergoing thoracic surgery without complications and those with complications must be both highly specific and sensitive. Clearly, the difference between patients at opposite ends of the population curves is easy to identify. Spirometry can be helpful for screening, although it is not a very discriminating test. If patients fall in the overlap region between the populations, however, it is impossible to discern the risks with any certainty using low-yield tests. A test with higher sensitivity, specificity, and predictive values is necessary to ascertain such marginal differences. With this kind of analysis at hand, preoperative testing can be divided into three predictive value groups. Calculating the predictive value of each preoperative test can provide a comparative measure of usefulness of discriminative power (Table 1). In this way, spirometry, blood gas analysis, and stair climbing tolerance are shown to be poor predictors of outcome. An intermediate predictive value can be achieved using diffusion capacity, exercise-induced decreases in O2 saturation, and exercise PVR. High predictive value can be accomplished with combination indexes (PPP, possibly PRQ), measurement of VO2 at 40 watts of exercise, or VO2max. Logic dictates a step-wise preoperative evaluation using prediction value analysis (Fig.4). A flow decision chart for the preoperative evaluation of patients for pulmonary resection begins with exercise oximetry, spirometry, and blood gas analysis as general screening tests to separate those patients at minimal or no risks for complications from those patients that require further evaluation. Functional indexes (PPP, PRQ) or exercise testing can aid further in the selection of those patients in whom a nonsurgical option should be considered. Flow decision chart for the preoperative evaluation of patients for pulmonary resection should continue to evolve as new information about outcome studies is gathered. Examination of outcome data will provide us with reduction of the size of the nonoperable population, so that we can deny only those patients who truly pose a prohibitive risk.     

Interpreting the chi-square statistics reported in the many-faceted Rasch model

The different chi-square statistics reported in the many-faceted Rasch model analysis are presented and interpreted. In addition, other chi-square summary values are computed and presented for interpretation of facets. The chi-square values are useful for determining: (1) the significance of a facet in the Rasch model; (2) the significant contribution of facet main and interaction effects; (3) differences among facet elements; and (4) identifying the specific facet interaction adjustments to the subjects' calibrated logit ability measure.     

Sociodemographic factors and the variation in syphilis rates among US counties, 1984 through 1993: an ecological analysis

OBJECTIVES: Syphilis in the United States is focally distributed, with high incidence rates in the South and in metropolitan areas nationwide. In this study an ecological analysis, using the county as the unit of analysis, was performed to generate hypotheses about community-level determinants of syphilis rates. METHODS: Bivariate rank correlations and multivariate, backward stepwise elimination linear regressions were performed. Mean annual incidence of primary- and secondary-stage syphilis in a county was the dependent variable, and county sociodemographic characteristics (from census data) were the independent variables. RESULTS: In the multivariate regression model, sociodemographic characteristics accounted for 71% of the variation in syphilis rates among counties. With other factors accounted for, the most highly correlated characteristics were percentage non-Hispanic Black population, county location in the South, percentage of the population that was urban, percentage Hispanic population, and percentage of births to women younger than 20 years. CONCLUSIONS: Most of the variation in syphilis rates among counties is accounted for by sociodemographic characteristics. Identification and remediation of modifiable health determinants for which these factors are markers are needed to improve the health status of these populations.     

Rheumatoid nodules: MR/pathological correlation

A 62-year-old female who had a complaint of palpitation was diagnosed as bicuspid aortic stenosis and left single coronary artery by the echocardiographic examination, cardiac catheterization study and coronary artery angiography. Aortic valve replacement was performed and the patient was discharged 22 days after surgery with good post-operative course. Preoperative coronary artery angiography was important in the case of aortic valvular disease.     

Forgetting in rats following medial septum or mammillary body damage.

Examined the effects of medial septal (MS) and mammillary body (MB) radio-frequency lesions in an automated delayed-matching-to-sample (DMTS) procedure using lever-position stimuli and rats. Memory performance pre- and postsurgery was assessed with a negative exponential decay function fitted to bias-free measures of recognition. Part 1 showed that MS, but not MB or sham-control surgery, impaired DMTS performance. This impairment in the MS group was best characterized as an increase in the rate of forgetting. Part 2 examined the interaction between MS and MB lesion effects and proactive interference arising from responses made on the previous DMTS trial. The results indicated that proactive interference effects were similar for all groups. These results provide further support for the critical role of the MS region in memory function but indicate that damage to this brain region does not disrupt memory function through a heightened sensitivity to proactive interference. (PsycINFO Database Record (c) 2010 APA, all rights reserved)