Molecular typing shows a high level of HLA class I incompatibility in serologically well matched donor/patient pairs: implications for unrelated bone marrow donor selection

In comparison with HLA-matched sibling bone marrow transplants, unrelated donor transplants are associated with increased graft-versus-host disease and graft failure. This is likely in part due to HLA incompatibilities not identified by current matching strategies. High resolution DNA-based typing methods for HLA class II loci have improved donor selection and treatment outcome in unrelated donor bone marrow transplantation. By using DNA-based typing methods for HLA-A and -B on a cohort of 100 potential bone marrow donor/patient pairs, we find that serological typing for HLA class I is limited in its ability to identify incompatibilities in unrelated pairs. Furthermore, the incompatibilities identified are associated with the presence at high frequency of alloreactive cytotoxic T-lymphocyte precursors. DNA typing also indicates that HLA-C mismatches are common in HLA-A and -B serologically matched pairs. Such mismatches appear to be significantly less immunogenic with respect to cytotoxic T-lymphocyte recognition, but are expected to influence natural killer cell activity. Thus, improved resolution of HLA class I shows many previously undisclosed mismatches that appear to be immunologically functional. Use of high resolution typing methods in routine matching is expected to improve unrelated donor selection and transplant outcome.     

Measurement of cytotoxic T lymphocyte precursor frequencies reveals cryptic HLA class I mismatches in the context of unrelated donor bone marrow transplantation

OBJECTIVE: Type 2 diabetes is a slowly progressive disease, in which the gradual deterioration of glucose tolerance is associated with the progressive decrease in beta-cell function. Hyperglycemia per se has deleterious effects on both beta-cell function and insulin action, which are partially reversible by the short-term control of blood glucose levels. We hypothesized that the induction of euglycemia, using intensive insulin therapy at the time of clinical diagnosis, could lead to a significant improvement in insulin secretion and action and thus alter the clinical course of the disease. RESEARCH DESIGN AND METHODS: Thirteen newly diagnosed diet-unresponsive type 2 diabetic patients were treated with continuous subcutaneous insulin infusion (CSII) for 2 weeks and followed longitudinally while being treated with diet alone. RESULTS: Four patients were considered therapeutic failures since CSII failed to induce euglycemia (n = 1) or glucose control deteriorated within 6 months after CSII (n = 3). The remaining nine patients were maintained on diet alone with adequate control from 9 to > 50 months (median +/- SE, 26 +/- 4.8 months). In five patients, glycemic control deteriorated after 9-36 months, but a repeat 2-week CSII treatment reestablished control in four patients. One of these patients underwent a third CSII treatment 13 months later. At the time this article was written, six patients of the initial group were still controlled without medication 16-59 months (median +/- SE, 45.5 +/- 6.6 months) after the initiation of treatment. Body weight remained unchanged in all patients. CONCLUSIONS: These findings suggest that in a significant proportion of type 2 diabetic patients who fail to respond to dietary measures, short-term intensive insulin treatment can effectively establish responsiveness, allowing long-term glycemic control without medication. Further studies are required to establish whether simpler treatment regimens could be equally effective. If the hypothesis offered here finds support, present approaches to the management of newly diagnosed type 2 diabetes may need to be revised.     

Protein-protein and protein-DNA interactions in the type I restriction endonuclease R.EcoR124I

The type I restriction-modification system EcoR124I recognizes and binds to the split DNA recognition sequence 5'-GAAN(6)RTCG-3'. The methyltransferase, consisting of HsdM and HsdS subunits with the composition M2S, can interact with one or more subunits of the HsdR subunit to form the endonuclease. The interaction of the methyltransferase with HsdR has been investigated by surface plasmon resonance, showing that there are two non-equivalent binding sites for HsdR which differ in binding affinity by at least two orders of magnitude. DNA footprinting experiments using Exonuclease III suggest that the addition of HsdR to the methyltransferase (at a stoichiometry of either 1:1 or 2:1) increases the stability of the resulting DNA-protein complex but does not increase the size of the footprint. More extensive in situ footprinting experiments using copper-phenanthroline on the DNA-protein complexes formed by M2S, R1M2S and R2M2S also show no difference in the detailed cleavage pattern, with approximately 18 nucleotides protected on both strands in each complex. Thus the HsdR subunit(s) of the endonuclease stabilise the interaction of the M2S complex with DNA, but do not directly contribute to DNA binding. In addition, the thymidine nucleotide in the tetranucleotide recognition sequence GTCG is hyper-reactive to cleavage in each case, suggesting that the DNA structure in this region is altered in these complexes.     

The Dynamics of Indonesia's Urbanisation, 1980-2006

This study examines continuity and change in patterns of Indonesia's urbanisation during the boom economy until the decentralisation era, using data mainly from the National Population Census 1980-2000 and from the Village Potential (PODES) 2006. Urbanisation in Indonesia is still characterised by a heavy concentration of the urban population in a few large cities, notably the Jakarta Metropolitan Area (JMA), which might reflect an integration of Jakarta into the global economy. It might also reflect an interurban disparity, between large and smaller cities. The population on the fringes of large cities is growing rapidly, while in the inner cities it is increasing at a very low rate of growth. Urban spatial development in Java is shaping belts, which connect many of the large cities. The intermediate cities and small towns on the outer islands have a relatively higher population growth rate compared with those in Java, which might suggest that those towns and cities are playing a more significant role in regional development.     

Telephone administration of the SF-36 health survey: validation studies and population norms for adults in Queensland

The Rand Corporation medical outcomes short-form 36 health survey (SF-36) is a multidimensional measure of self-perceived general health status, which has been validated in adult populations in the United States and Great Britain, and, more recently, in an Australian population. The SF-36 is increasingly being used in health outcomes research internationally, mainly as a self-administered tool, and clearly has potential for use in Australia. This study aimed to assess the acceptability, reliability and validity of telephone administration of the instrument in the Queensland adult population, and to provide reliable population norms. We report the results of a telephone survey in which we interviewed 12,793 adults. It was the first large-scale, statewide application of the SF-36 in Australia. A response rate of 82 per cent was achieved, and the SF-36 satisfied psychometric criteria for reliability and construct validity. Population norms broken down by age and sex are provided. They will be important for the interpretation of future studies using the SF-36 in particular population or patient groups.     

Performance heuristics for GR(1) synthesis and related algorithms

Acta Informatica - Reactive synthesis for the GR(1) fragment of LTL has been implemented and studied in many works. In this work we present and evaluate a list of heuristics to potentially reduce...     

Harnessing the Excellent Mechanical,Barrier and Antimicrobial Properties of Zinc Oxide (ZnO) to Improve the Performance of Starch-based Bioplastic

ABSTRACT

The inherent properties of starch which are poor mechanical properties and its hydrophilicity that leads to poor long-term water absorption, fostered the incorporation of additives into starch-based bioplastic to enhance its mechanical and barrier properties. Zinc oxide (ZnO) nanoparticle as a lightweight material that is biocompatible, nontoxic, cost-effective and exhibit strong antibacterial activity can be considered as nano reinforcement of starch-based bioplastic. The present work studied the reinforcing effect of ZnO on the physical, mechanical and antibacterial properties of starch-based bioplastic. Bioplastic was prepared by melt-mixing starch and glycerol (3:1, w/w) with ZnO (1%, 2%, 3%, 4% and 5%, w/w). Bioplastic density and water contact angle increased with the increase of ZnO concentration. Bioplastic with the addition of 4% ZnO showed the lowest moisture content of 3.45%. Moreover, the decomposition temperature of bioplastic with ZnO increased slightly which indicated the higher stability. Mechanical properties evaluation showed that bioplastic with addition of ZnO had higher tensile strength than that without ZnO where 4% ZnO exhibited the highest tensile strength of 10.29 MPa with elongation of 5.69%. Cross-section microstructure after tensile test showed that ZnO was fairly dispersed in starch matrix that implied the increase of the mechanical properties of bioplastic. FTIR spectra exhibited that the intermolecular interaction in bioplastics occurred through C–H, C=O, C–O–H and O–H groups. In addition, biodegradability tests of bioplastic showed that the growth of microbes decreased in the presence of ZnO due to the nature of ZnO as an antibacterial compound. The results showed that ZnO played a key role in reinforcing the physical, mechanical and antibacterial properties of starch-based bioplastic.     

Robotic System for Handling Infectious Clinical and Pre-Clinical Serum Samples

The Bioanalytical Laboratory at the Schering-Plough Research Institute is a service laboratory which performs drug level measurements in serum in support of pre-clinical toxicological tests, as well as human clinical trials for anti-viral compounds. A new robot system for the laboratory had two external constraints put on it, besides those typical for a robotic system: since it handled infectious serum samples, it needed to be contained within a biosafety cabinet, and all data handling and labeling were subject to regulatory oversight. The result is a robot cell consisting of a large custom biological safety hood with an integrated track mounted robot, refrigerated storage, mixing, 2-D bar code reading, and automated pipetting. In addition to the material handling hardware, sample labeling software was developed for use at sample collection sites within Schering-Plough, and at external contract laboratories.     

A test of behavioral family therapy to augment exposure for combat-related posttraumatic stress disorder.

This study tested a family-based skills-building intervention in veterans with chronic combat-related posttraumatic stress disorder (PTSD). Veterans and a family member were randomly assigned to 1 of 3 conditions: (a) waiting list, (b) 18 sessions of twice-weekly exposure therapy, or (c) 18 sessions of twice-weekly exposure therapy followed by 16 sessions of behavioral family therapy (BFT). Participation in exposure therapy reduced PTSD positive symptoms (e.g., reexperiencing and hyperarousal) but not PTSD negative symptoms. Positive symptom gains were maintained at 6-month follow-up. However, participation in BFT had no additional impact on PTSD symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)