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Biomedical subjects

B Metcalf

Publications and source records attributed to B Metcalf.

12 recordsLinked to original sources
PubMed2003

Testing the accelerator hypothesis: the relationship between body mass and age at diagnosis of type 1 diabetes.

OBJECTIVE: Previous reports have predicted greater risk of type 1 diabetes among people who were heavier as young children. The Accelerator Hypothesis predicts earlier onset in heavier people, without necessarily a change in risk, and views type 1 and type 2 diabetes as the same disorder of insulin resistance, set against different genetic backgrounds. Insulin resistance is a function of fat mass, and increasing body weight in the industrialized world has been accompanied by earlier presentation (i.e., acceleration) of type 2 diabetes. We wanted to establish whether increasing body weight was also associated with the earlier presentation of type 1 diabetes, as the Accelerator Hypothesis would predict. RESEARCH DESIGN AND METHODS: The relationships between fatness and age at diagnosis were examined in context of birth weight, weight change since birth, weight at diagnosis, BMI at diagnosis, and BMI 12 months later in 94 children aged 1-16 years (49 boys and 45 girls) presenting for management of acute-onset type 1 diabetes. RESULTS: BMI standard deviation score (SDS) at diagnosis, weight SDS change since birth, and BMI SDS 12 months later were all inversely related to age at presentation (r = -0.39 to -0.40, P < 0.001). The boys were significantly fatter than the girls (BMI SDS 0.56 vs. -0.08, respectively; P = 0.006) and presented with diabetes at a significantly younger age (6.74 vs. 8.32 years, respectively; P < 0.05). The sex difference in age at diagnosis, however, disappeared when corrected for BMI (P = 0.31), suggesting that fatness or something related to it was the responsible factor. CONCLUSIONS: The data are consistent with the hypothesis that the age at presentation of type 1 diabetes is associated with fatness. The implications for prevention of type 1 diabetes may be important.

Adolescent↗
PubMed2001

A randomized controlled trial of a community-based consultation service to prevent falls.

BACKGROUND: Multifaceted programs that combine assessment with interventions have been shown to reduce subsequent falls in some clinical trials. We tested this approach to see whether it would be effective if offered as a consultation service using existing health care resources. METHODS: The subjects of this randomized controlled trial had to be aged 65 years or more and had to have fallen within the previous 3 months. They were randomly assigned to receive either usual care or the intervention, which consisted of in-home assessment in conjunction with the development of an individualized treatment plan, including an exercise program for those deemed likely to benefit. The primary outcomes were the proportion of participants who fell and the rate of falling during the following year. Visits to the emergency department and admissions to hospital were secondary outcomes. RESULTS: One hundred and sixty-three subjects were randomly assigned to either the control or the intervention group, and 152 provided data about their falls. There were no significant differences between the control and intervention groups in the cumulative number of falls (311 v. 241, p = 0.34), having one or more falls (79.2% v. 72.0%, p = 0.30) or in the mean number of falls (4.0 v. 3.2, p = 0.43). Analysis of secondary outcomes (health care use) also showed no significant differences between the intervention group and the control group. In the Cox regression analysis, there was no significant difference between the groups in the proportion of subjects having one or more falls (p = 0.55), but there was a significantly (p < 0.001) longer time between falls in the intervention group. In a post hoc subgroup analysis, subjects with more than 2 falls in the 3 months preceding study entry who had been assigned to the intervention group were less likely to fall (p = 0.046) and had a significantly longer time between falls (p < 0.001), when compared with the group who received usual care. INTERPRETATION: The intervention did not decrease significantly the cumulative number of falls, the likelihood of participants having at least one fall over the next year or the mean number of falls. It did increase significantly the time between falls in a survival analysis when age, sex and history of falling were used as covariates.

Accidental Falls↗
PubMed2000

The impact of genomics on drug discovery.

High-throughput gene sequencing has revolutionized the process used to identify novel molecular targets for drug discovery. Thousands of new gene sequences have been generated but only a limited number of these can be converted into validated targets likely to be involved in disease. We describe here some of the approaches used at SmithKline Beecham to select and validate novel targets. These include the identification of selective tissue gene product expression, such as for cathepsin K, a novel osteoclast-specific cysteine protease. We also describe the discovery and functional characterization of novel members of the G-protein coupled receptor superfamily and their pairing with natural ligands. Lastly, we discuss the promises of gene microarrays and proteomics, developing technologies that allow the parallel analyses of tissue expression patterns of thousands of genes or proteins, respectively.

Animals↗
PubMed1999

Tele-talk: a communication device for the persons with hearing disabilities.

Tele-Talk is a device designed to allow a person with hearing disabilities to communicate using the telephone, with a minimum of effort and without requiring a multitude of special equipment. This device provides a previously unavailable link for the hearing disabled to communicate directly over telephone lines. Tele-Talk has the extra capability of operating in live conference situations using microphone input. Today, most devices designed for the hearing-impaired are dependent on both communicants' owning/operating identical set-ups. If an accessory item is missing or misplaced, communication breaks down. Tele-Talk answers the need to permit transparent hearing assistance via the telephone.

Communication↗
PubMed1995

Immunogenicity of genetically engineered glutathione S-transferase fusion proteins containing a T-cell epitope from diphtheria toxin.

Glutathione S-transferase (GST) has been shown to induce a marginal antibody response in experimental animals as well as partial protection against a number of parasitic worms, including Schistosoma and Fasciola species. The objective of our study was to increase the immunogenicity of GST by adding heterologous T-cell epitopes at the carboxy terminus of the protein. We generated recombinant GST proteins by attaching one or three tandem repeats of a T-cell epitope of CRM197, a nontoxic variant of diphtheria toxin. This T-cell epitope encoding the region of amino acids 366 to 383 of CRM197, when contained in a GST fusion protein and/or after purification as a recombinant peptide, retained the ability to induce a CRM197-specific T-cell response. The fusion protein containing a single T-cell epitope induced a strong T-cell proliferative response to GST and also enhanced anti-GST antibody production in mice. The addition of three repeats of the epitope did not augment the responses when compared with the responses of GST itself. The results suggest that the addition of a single T-cell epitope to a larger protein like GST increases the immunogenicity of the protein.

Amino Acid Sequence↗
PubMed1976

Increased phosphorylated components of erythrocyte membrane spectrin band II with reference to Duchenne muscular dystrophy.

Increased erythrocyte band II phosphorylation has been demonstrated in patients with Duchenne muscular dystrophy (DMD). Band II has been purified by preparative sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Isoelectric focusing of purified band II from which SDS has been removed reveals heterogeneity. Band II migrates as multiple bands on isoelectric focusing gels and as a single band on SDS-polyacrylamide gels. The increased phosphorylation in DMD does not occur uniformly in all components of band II. Highly phosphorylated components of band II are present in DMD in which only minimal phosphorylation occurs in controls. These results suggest the presence of an abnormal band II substrate in erythrocyte membranes from DMD patients.

Adult↗
PubMedDate not supplied

Aging and meaning in life: examining the concept.

To make sense of their existence in the face of adversity and chaos or during times of relative calm, human beings seek meaning. Meaning has been identified as a significant factor in health and well-being in later years. Engaging in an intensive literature search about meaning in later life constituted the beginning step for a qualitative research study. By studying how older people experience meaning in their lives, we may learn more about the human experiences of joy and hope and their capacity to respond to opportunities and manage problems in their lives.

Adaptation, Psychological↗