The Complete Set of Predicted Genes from Saccharomyces cerevisiae in a Readily Usable Form

Nearly all of the open reading frames (ORFs) of the yeast Saccharomyces cerevisiae have been synthesized by PCR using a set of ~6000 primer pairs. Each of the forward primers has a common 22-base sequence at its 5′ end, and each of the back primers has a common 20-base sequence at its 5′ end. These common termini allow reamplification of the entire set of original PCR products using a single pair of longer primers—in our case, 70 bases. The resulting 70-base elements that flank each ORF can be used for rapid and efficient cloning into a linearized yeast vector that contains these same elements at its termini. This cloning by genetic recombination obviates the need for ligations or bacterial manipulations and should permit convenient global approaches to gene function that require the assay of each putative yeast gene.     

Altered feeding responses in mice with targeted disruption of the dopamine-3 receptor gene

Dopamine signaling has been implicated in the control of food intake and body weight. In particular, dopamine is important in the control of meal size and number and is thought to mediate the response to metabolic deprivation states. In the present experiments, the authors assessed the role of the dopamine-3 receptor (D3R) in the feeding responses to 2-deoxy-D-glucose, mercaptoacetate, and peripheral insulin. All 3 compounds increased food intake in wild-type mice, but the hyperphagic responses were blunted in D3R-/- mice. In other experiments, D3R-/- mice were hyperresponsive to the administration of amylin and leptin relative to wild-type mice. These results support the hypothesis that D3Rs chronically inhibit the effects of adiposity hormones, thereby contributing to a net anabolic state.     

Hospital of the futureSM—Not just technology “talk”

Technology is gaining increasing attention and competitive importance in the healthcare industry, but healthcare administrators need more than just talk to make effective technology investments. Andersen Consulting and the American College of Healthcare Executives have created Hospital of the Future^SM, in Dallas, Texas, as a dynamic, evolving research and demonstration forum that allows healthcare administrators and providers to see potential technology solutions in action—in healthcare settings specifically designed to look and feel like the real thing. This article discusses the functionality and technical structure of Hospital of the Future, as well as the integration issues among disparate healthcare systems addressed in developing the display.     

Reform demands strategic action at the regional level

Those who understand the primary forces driving reform are in a better position to survive the transformation underway. To succeed, organizations must use this knowledge and act strategically at the regional level.     

Validity and reproducibility of a food frequency interview in a Multi-Cultural Epidemiology Study

PURPOSE: There is limited support for the validity and reproducibility of dietary assessment in culturally diverse populations. The goal of this study was to evaluate the comparative validity and reproducibility of a Food Frequency Questionnaire (FFQ) used in the observational, multi-cultural Insulin Resistance Atherosclerosis Study (IRAS). METHODS: Women (n = 186) were approximately equally distributed by ethnicity from one urban center (African Americans and non-Hispanic whites) and one rural center (Hispanics and non-Hispanic whites). The IRAS FFQ was modified from the National Cancer Institute Health Habits and History Questionnaire to include ethnic and regional foods. Validity was assessed by comparing dietary values, including supplements, obtained from the FFQ to the average intake estimated from a series of 8 24-hour dietary recalls collected by telephone over the same 1-year period. Reproducibility was assessed among women who reported no change in their usual diet (n = 133) by comparing data from the original IRAS FFQ (in-person) with the FFQ administered for the validity study (two to four years later, by telephone). RESULTS: Correlation coefficients for validity were statistically significant for most nutrients (mean r = 0.62 urban non-Hispanic white, 0.61 rural non-Hispanic whites, 0.50 African American, 0.41 Hispanic) and did not differ among subgroups of obesity or diabetes status. The median correlation coefficient for the total sample was 0.49. Correlations were lower for women with less than 12 years of education (mean r = 0.30; median r = 0.25). The lower correlations among Hispanics was largely explained by the lower educational attainment in that sample. For reproducibility, the mean correlation for nutrients evaluated was r = 0.62 (median r = 0.63) and did not differ for subgroups. CONCLUSIONS: Although educational attainment must be considered, the IRAS FFQ appears to be reasonably valid and reliable in a diverse cohort.     

Proliferative activity in craniopharyngiomas: clinicopathological correlations in adults and children

BACKGROUND: Craniopharyngiomas are slow-growing, locally invasive intracranial tumors that can generate considerable morbidity, and recurrences are often difficult to manage. Because reliable morphologic criteria for accurately predicting the clinical outcome of these tumors are lacking, we evaluated the growth potential of craniopharyngiomas by measuring their proliferative activity based on MIB-1 immunostaining for the Ki-67 antigen, which is expressed during all phases of the cell cycle except G(0.) METHODS: Paraffin sections from 37 cases of craniopharyngiomas were immunostained with the monoclonal antibody MIB-1, and a labeling index was derived in each case from an the with the highest labeling. RESULTS: MIB-1 immunoreactivity was mainly confined to the peripheral palisaded epithelium of craniopharyngiomas. In adult craniopharyngiomas, MIB-1 labeling indices (MIB-LI) varied from 0.1% to 34.6% (mean 8.9%; SD 9. 8), and in pediatric tumors the indices ranged from 1.8% to 15.0% (mean 6.3%; SD 3.7). MIB-LI was not found to be an independent predictor of recurrence, although in all the pediatric cases that recurred, MIB-LI in the second specimen was greater. CONCLUSIONS: The actively proliferating compartment in craniopharyngiomas seems to be the peripheral palisaded epithelium. Low MIB-LI observed in the majority of tumors is in concordance with the slow growth and low-grade invasiveness associated with craniopharyngiomas. However, unlike other intracranial neoplasms, where Ki-67 labeling indices have been useful in predicting tumor behavior, a clear relationship could not be demonstrated between MIB-1 immunoreactivity, morphological features and clinical outcomes in adults or children with craniopharyngiomas.     

Precipitins to an aflatoxin-producing strain of aspergillus flavus in patients with malignancy

Summary Serum samples from 121 patients in whom malignant disease had been diagnosed, were assayed for precipitins to fungal isolates from leukemia-associated environments. Control sera were from age-, sex-, and race-matched patients with no history of malignant disease. Sera from 36 (30%) malignancy patients and seven (6%) controls yielded a precipitin band to an aflatoxin-producing Aspergillus flavus isolate from a leukemia-associated house ², p<0.05%). No significant numbers of precipitins were obtained to either of the other fungal isolates from that and another such house.Although A. fumigatus has frequently been incriminated as a source of infection in patients with malignancy, only 9% of malignancy patients had a precipitin response to it, as did 1.6% of controls. Also, the presence of the precipitins to A. flavus was not connected with past radiation or imunosuppressive therapy. However, among patients with precipitins to A. fumigatus there was a higher death rate in the year following the study. Precipitins to A. flavus may be related to heavy environmental exposure possibly leading to aflatoxin exposure which may contribute to development of malignancy through immunosuppressive effects.     

Chronic myopathy due to immunoglobulin light chain amyloidosis

Amyloid myopathy associated with a plasma cell dyscrasia is a rare cause of muscle hypertrophy. It can be a challenging diagnosis, since pathological findings are often elusive. In addition, the mechanism by which immunoglobulin light-chain deposition stimulates muscle overgrowth remains poorly understood. We present a 53-year old female with a 10-year history of progressive generalized muscle overgrowth. Congo-red staining and immunohistochemistry revealed perivascular lambda light chain amyloid deposits, apparent only in a second muscle biopsy. The numbers of central nuclei and satellite cells were increased, suggesting enhanced muscle progenitor cell formation. Despite the chronicity of the light chain disease, the patient showed complete resolution of hematologic findings and significant improvement of her muscle symptoms following autologous bone marrow transplantation. This case highlights the importance of early diagnosis and therapy for this treatable cause of a chronic myopathy with muscle hypertrophy.