Trends in mortality of childhood-onset insulin-dependent diabetes mellitus in Leicestershire: 1940-1991

The relative risk of death by calendar date of diagnosis was investigated in a population-based incident cohort of 845 (463 males:382 females) IDDM diagnosed in Leicestershire before the age of 17 years between 1940 and 1989. The mortality status of 844 (99.9%) patients was determined as of the 31 December 1991, representing 14,346 person-years of risk. Trends in relative risk of death were investigated using Cox proportional hazards modelling for within cohort comparisons and age/sex and calendar time adjusted standardized mortality ratios (SMR) using generalized linear modelling for external comparisons. Median age at diagnosis was 10 years (range 3 months to 16 years); median duration of diabetes 15 years (range 1-51 years). Forty-four patients had died (5.2%; median age at death 31 years, range 11-51 years). A further four patients died at presentation (within 24 h) from ketoacidosis and are excluded from all analyses. Calendar date of diagnosis was found to be an important predictor of mortality. Adjusting for attained age there was evidence of a decline in relative risk of death with calendar date of diagnosis of 3.4% (95% CI, 0.005-6.9%) per annum, equivalent to a 32% fall per decade (95% CI, 5-51%), or 84% (95% CI, 21-97) from 1940 to 1989. The data are consistent with a large fall in mortality between the 1940s and 1950s representing over 50% of the total reduction in mortality between 1940 and 1991. Neither sex nor age at diagnosis were significant predictors of mortality. Over the study period 1940-89 the SMR (male and female combined) fell from 981 (541-1556) to 238 (60-953) relative to the general population. This population-based study shows that the prognosis for Type 1 (insulin-dependent) diabetes mellitus has improved markedly over the period 1940-1991.     

Effects of acid leaching treatment of soda-lime silicate glass on crack initiation and fracture

Water or acid soaking surface treatments have been shown to increase the mechanical strength of soda-lime silicate (SLS) glasses. This increase in strength has traditionally been attributed to effects related to residual stress or changes in fracture resistance. In this work, we report experimental data that cannot be explained based on the existing knowledge of glass surface mechanics. In dry environments, annealed and acid-leached SLS surfaces have comparable crack initiation stress and fracture stress as measured by Hertzian indentation and biaxial bending tests, respectively. Yet, in the presence of humidity, acid-leached surfaces have higher failure stress than the annealed surfaces. This apparent enhancement in the crack resistance of the acid-leached surface of SLS glass in humid environments supports the hypothesis that acid-leached surface chemistry can lower the transport kinetics of molecular water to critical flaws.     

Purification, characterization, and high performance liquid chromatography assay of Salmonella glucose-1-phosphate cytidylyltransferase from the cloned rfbF gene

We report the purification and characterization of glucose-1-phosphate cytidylyltransferase, the first of five enzymes committed to biosynthesis of CDP-D-abequose from Salmonella enterica strain LT2. The purification was greatly facilitated by using a cloned rfbF gene encoding this enzyme. Pure enzyme was obtained by 64-fold enrichment in three chromatography steps. The NH2-terminal sequence of the purified enzyme was in agreement with the sequence predicted from the nucleotide sequence of the rfbF gene. The SDS-polyacrylamide gel electrophoresis estimated subunit M(r) of 31,000 agrees well with the M(r) of 29,035 calculated from the amino acid composition deduced from the nucleotide sequence of the rfbF gene. The glucose-1-phosphate cytidylyltransferase catalyzes a reversible bimolecular group transfer reaction and steady-state kinetic measurements, including product inhibition patterns, indicate that this reaction proceeds by a "ping-pong" type of mechanism. The Km values for CTP, alpha-D-glucose 1-phosphate, CDP-D-glucose, and pyrophosphate are 0.28, 0.64, 0.11, and 1.89 mM, respectively.     

Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-specific cytolytic T lymphocytes

Characterization of cytolytic T lymphocyte (CTL) responses to tumor antigens has been impeded by a lack of direct assays of CTL activity. We have synthesized reagents ("tetramers") that specifically stain CTLs recognizing melanoma antigens. Tetramer staining of tumor-infiltrated lymph nodes ex vivo revealed high frequencies of tumor-specific CTLs which were antigen-experienced by surface phenotype. In vitro culture of lymph node cells with cytokines resulted in very large expansions of tumor-specific CTLs that were dependent on the presence of tumor cells in the lymph nodes. Tetramer-guided sorting by flow cytometer allowed isolation of melanoma-specific CTLs and confirmation of their specificity and their ability to lyse autologous tumor cells. Our results demonstrate the value of these novel reagents for monitoring tumor-specific CTL responses and for generating CTLs for adoptive immunotherapy. These data also indicate that strong CTL responses to melanoma often occur in vivo, and that the reactive CTLs have substantial proliferative and tumoricidal potential.     

OBSERVER: An Approach for Query Processing in Global Information Systems Based on Interoperation Across Pre-Existing Ontologies

There has been an explosion in the types, availability and volume of data accessible in an information system, thanks to the World Wide Web (the Web) and related inter-networking technologies. In this environment, there is a critical need to replace or complement earlier database integration approaches and current browsing and keyword-based techniques with concept-based approaches. Ontologies are increasingly becoming accepted as an important part of any concept or semantics based solution, and there is increasing realization that any viable solution will need to support multiple ontologies that may be independently developed and managed. In particular, we consider the use of concepts from pre-existing real world domain ontologies for describing the content of the underlying data repositories. The most challenging issue in this approach is that of vocabulary sharing, which involves dealing with the use of different terms or concepts to describe similar information. In this paper, we describe the architecture, design and implementation of the OBSERVER system. Brokering across the domain ontologies is enabled by representing and utilizing interontology relationships such as (but not limited to) synonyms, hyponyms and hypernyms across terms in different ontologies. User queries are rewritten by using these relationships to obtain translations across ontologies. Well established metrics like precision and recall based on the extensions underlying the concepts are used to estimate the loss of information, if any.     

Traveling the Semantic Web through Space, Time, and Theme

In this installment of Semantics and Services, we further develop the idea of spatial, temporal, and thematic (STT) processing of semantic Web data and describe the Web infrastructure needed to support it. Starting from Ramesh Jain's vision of the EventWeb as a view of what's possible with a Web that better accommodates all three dimensions of event-related information (thematic, spatial, and temporal), we outline the architecture needed to support it and current research that aims to realize it.     

The use of angiostatic steroids to inhibit cartilage destruction in an in vivo model of granuloma-mediated cartilage degradation

Angiogenesis is an important component of the development of chronic inflammatory diseases such as rheumatoid arthritis. It is known that clinically used anti-rheumatic drugs exert, in part, effects on the angiogenic response. Little work, however, has investigated the potential of experimental angiostatic therapies in chronic inflammatory disease models. The effect of one such angiostatic treatment, cortisone combined with heparin, was tested in an in vivo model of granuloma-mediated cartilage degradation. Angiostatic treatment significantly retarded the growth of granulomatous tissue, mononuclear cell influx into the granuloma, and the degradation of juxtaposed cartilage. This correlated with a decrease in the vascularity of the granulomatous tissue. Modulation of this component of pathogenesis of "angiogenesis-dependent disease" may be useful as a new therapeutic approach.     

Grafting of enzymes on collagen films using Woodward''s reagent "K" and a water-soluble carbodiimide derivative

Two new methods of activation were developed to graft enzymes on collegen films. They involved chemical modifications of surface groups of collagen either by Woodward's reagent "K" or by EDC, a water-soluble derivative of carbodiimide. EDC was a better coupling agent and a detailed study was conducted with this agent. It could be used either in a global method of activation and coupling, or in a two-step procedure of activation of collagen, followed by spontaneous coupling of enzyme. All enzymes tested were successfully bound: malate dehydrogenase, lactate dehydrogenase, aspartate aminotransferase, urease, creatine kinase, hexokinase. The influence on the yield of grafted enzyme, of pretreatment of films, time and temperature of EDC activation, concentration of EDC and enzyme, protecting agents was studied. Stability of enzyme activity on storage was greatly increased after grafting. A co-grafted dual system creatine kinase/heoxkinase, was achieved which exhibited a good efficiency. A striking renaturing process at 0-4degreesC after thermal denaturation, was observed with hexokinase.