Is the physical functioning of older adults with diabetes associated with the processes and outcomes of care? Evidence from Translating Research Into Action for Diabetes (TRIAD).

AIMS: To examine the relationship between physical function limitations and diabetes self-management, processes of care and intermediate outcomes in adults ≥ 65 years of age with Type 2 diabetes. METHODS: We studied 1796 participants 65 years of age and older in managed care health plans enrolled in Translating Research into Action for Diabetes (TRIAD). Physical functioning was assessed at baseline with the Physical Component Summary of the Short Form-12 Health Survey. Diabetes self-management was assessed with follow-up surveys, and processes of care (eye examinations, urine microalbumin testing, foot examinations, etc.) and intermediate health outcomes (HbA(1c), blood pressure, LDL cholesterol) were assessed with medical chart reviews. Multivariate regression models were constructed to examine the associations between physical function limitations and outcomes. RESULTS: Frequency of eye examinations (odds ratio 0.69, 95% CI 0.49-0.99) was the only process of care that was worse for participants with physical function limitations (n = 573) compared with those without limitations (n = 618). Neither self-management nor intermediate outcomes differed by whether patients had or did not have physical function limitations. CONCLUSION: Limitations in physical functioning as assessed by the Short Form-12 were not associated with substantial difference in diabetes care in adults ≥ 65 years of age enrolled in managed care health plans.

Sample Tracking in an Automated Cytogenetic Biodosimetry Laboratory for Radiation Mass Casualties.

Chromosome aberration-based dicentric assay is expected to be used after mass casualty life-threatening radiation exposures to assess radiation dose to individuals. This will require processing of a large number of samples for individual dose assessment and clinical triage to aid treatment decisions. We have established an automated, high-throughput, cytogenetic biodosimetry laboratory to process a large number of samples for conducting the dicentric assay using peripheral blood from exposed individuals according to internationally accepted laboratory protocols (i.e., within days following radiation exposures). The components of an automated cytogenetic biodosimetry laboratory include blood collection kits for sample shipment, a cell viability analyzer, a robotic liquid handler, an automated metaphase harvester, a metaphase spreader, high-throughput slide stainer and coverslipper, a high-throughput metaphase finder, multiple satellite chromosome-aberration analysis systems, and a computerized sample tracking system. Laboratory automation using commercially available, off-the-shelf technologies, customized technology integration, and implementation of a laboratory information management system (LIMS) for cytogenetic analysis will significantly increase throughput.This paper focuses on our efforts to eliminate data transcription errors, increase efficiency, and maintain samples' positive chain-of-custody by sample tracking during sample processing and data analysis. This sample tracking system represents a "beta" version, which can be modeled elsewhere in a cytogenetic biodosimetry laboratory, and includes a customized LIMS with a central server, personal computer workstations, barcode printers, fixed station and wireless hand-held devices to scan barcodes at various critical steps, and data transmission over a private intra-laboratory computer network. Our studies will improve diagnostic biodosimetry response, aid confirmation of clinical triage, and medical management of radiation exposed individuals.

The replication inhibition activity of the WT1 tumor suppressor protein resides in its N-terminal 298 amino acid region, and does not require specific binding of the protein to the replication origin sequence.

Using the simian virus 40 replication origin as the model, it was reported previously that the Wilms' tumor suppressor protein WT1 can inhibit DNA replication. In the present study, we found that a hybrid protein (termed GAL4-WT1AE Z) consisting of the DNA-binding domain of the yeast transcription factor GAL4 fused in-frame with the N-terminal 298 amino acid (aa) transcriptional regulatory region of WT1 retained the ability to inhibit replication. The hybrid protein and the full-length WT1 inhibited replication without regard to the presence or absence of their binding sites in the replication origin region, indicating that inhibition of replication by the proteins does not require their specific binding to the origin region. The inhibition efficiency of the hybrid protein was the same as that of WT1, indicating that the replication inhibition activity resides in the N-terminal 298 aa region, and that the C-terminal zinc finger-containing DNA-binding domain of WT1 is functionally dispensable for this effect.

Intestinal toxicity of acrylonitrile: in vitro metabolism by intestinal cytochrome P450 2E1.

Acrylonitrile (VCN) is known to cause extensive gastrointestinal damage and tumors in rats. In this study the metabolism of VCN to cyanide (CN-) was characterized in the small intestinal mucosa. The majority of the metabolic reactivity was localized in the microsomal fraction and required reduced nicotinamide adenine dinucleotide phosphate for maximal activity. The intestinal metabolism of VCN to CN- was characterized with respect to VCN concentration, time, pH, and microsomal protein concentration. VCN metabolism to CN- was enhanced significantly by the addition of sulfhydryl compounds such as glutathione, cysteine, and D-penicillamine (10 mM) to 142, 161, and 189% of control, respectively. The intestinal bioactivation of VCN to CN- was enhanced by microsomes obtained from intestinal mucosa of phenobarbital (455% of control), beta-naphthoflavone (375% of control), 4-methylpyrazole (305% of control), or ethanol (165% of control)-treated rats. Addition of ethanol (80 mM) to incubation mixtures containing control or ethanol-induced microsomes resulted in significant inhibition of microsomal metabolism of VCN to CN- to 20 and 34% of control, respectively. Addition of dimethyl sulfoxide induced a similar inhibitory effect on VCN metabolism by control or ethanol-induced microsomes (8 and 26% of control, respectively). Furthermore, antibody to cytochrome P450 2E1, but not antibody to cyt P450 2B1, significantly inhibited VCN metabolism by ethanol-induced intestinal microsomes to about 25% of control. Mild inhibition (80-85% of control) of VCN metabolism was detected when antibody to cyt P450 2B1 or 2E1 was added to incubation mixtures containing Pb-induced intestinal microsomes. These findings indicate that extrahepatic tissues such as the intestinal mucosa are capable of metabolizing VCN to CN- and establish a major role of intestinal cyt P450, particularly cyt P450 2E1, in the intestinal metabolism of VCN to CN-.

Immunoglobulin gene rearrangements in acute lymphoblastic leukemia with the 9;11 translocation.

The recurring chromosomal 9;11 translocation [t(9;11) (p22;q23)] typically is associated with acute monoblastic leukemia, but a number of patients with acute lymphoblastic leukemia also have been reported to have the t(9;11). To investigate the cell lineage in the latter cases, we analyzed DNA from the leukemic cells of an 8-year-old girl with acute lymphoblastic leukemia and a t(9;11) for rearrangements of the immunoglobulin and T-cell receptor genes. Rearrangements of both immunoglobulin heavy-chain loci and of one lambda light-chain gene were detected, as well as deletions affecting both alleles of the kappa light-chain genes; T-cell receptor genes were in germline configuration. These results provide further evidence that the 9;11 translocation is not limited to myeloid lineage leukemia and may be observed in acute lymphoblastic leukemia.