Biomedical subjects
Publications and source records attributed to Michael Kidd.
The original recognition of the paired helical filaments is discussed and amplified. The original description of what are now the neuropil threads is mentioned. The ensuing importance of both these structures is emphasised and a morphology-based hypothesis of the development of the disease from the original stimuli is offered.
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The absolute and relative abundance of major histocompatibility complex class I-presented viral epitopes is important in the induction and maintenance of antiviral cytotoxic-T-lymphocyte (CTL) responses. We demonstrate that the supra-abundant HLA-A*0201-restricted peptide KLWESPQEI of the measles virus nonstructural C protein induces strong gamma interferon CD8(+)-T-cell responses in children with acute measles. However, longitudinal analysis indicates that these responses are only short-lived. Thus, some viral epitopes that can be immunodominant during primary infection may fail to establish memory CTL responses.
Immunization of newborns against viral infections may be hampered by ineffective CD8(+) T cell responses. To characterize the function of CD8(+) T lymphocytes in early life, we studied newborns with congenital human cytomegalovirus (HCMV) infection. We demonstrate that HCMV infection in utero leads to the expansion and the differentiation of mature HCMV-specific CD8(+) T cells, which have similar characteristics to those detected in adults. High frequencies of HCMV-specific CD8(+) T cells were detected by ex vivo tetramer staining as early as after 28 weeks of gestation. During the acute phase of infection, these cells had an early differentiation phenotype (CD28(-)CD27(+)CD45RO(+), perforin(low)), and they acquired a late differentiation phenotype (CD28(-)CD27(-)CD45RA(+), perforin(high)) during the course of the infection. The differentiated cells showed potent perforin-dependent cytolytic activity and produced antiviral cytokines. The finding of a mature and functional CD8(+) T cell response to HCMV suggests that the machinery required to prime such responses is in place during fetal life and could be used to immunize newborns against viral pathogens.
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We have previously reported that vitamin A supplementation with measles vaccine at age 9 months increases measles-specific antibody concentrations in children at age 18 months compared with placebo. We examined these children when they reached age 6-8 years. Fewer vitamin A-supplemented children had non-protective antibody concentrations (p=0.0095); among children with protective antibody levels, vitamin A-supplemented children tended to have higher geometric mean antibody titres (p=0.09). Thus, simultaneous administration of vitamin A and measles vaccine at age 9 months had a long-term effect on measles-specific antibody levels and may contribute to improved measles control in less-developed countries.
The immaturity of the immune system increases the susceptibility of young infants to infectious diseases and prevents the induction of protective immune responses by vaccines. We previously reported that Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination induces a potent Th1 response to mycobacterial Ags in newborns. In this study, we evaluated the influence of BCG on the response to unrelated vaccines given in early life. Newborns were randomly allocated to one of three study groups receiving BCG at birth, when infants received their first dose of hepatitis B and oral polio vaccines; at 2 mo of age, when infants received their first dose of diphtheria and tetanus vaccines; or at 4.5 mo of age, when immune responses to vaccines were measured. Administration of BCG at the time of priming markedly increased the cellular and Ab responses to the hepatitis B vaccine, but had only a limited influence on the cytokine response to tetanus toxoid and no effect on the Ab responses to tetanus and diphtheria toxoids. Although BCG induced a potent Th1-type response to mycobacterial Ags, it promoted the production of both Th1- and Th2-type cytokines in response to unrelated vaccines. The effect of BCG was apparent at the systemic level, as it increased the Ab response to oral polio vaccine. These results demonstrate that BCG influences the immune response to unrelated Ags in early life, likely through its influence on the maturation of dendritic cells.
BACKGROUND: While still in its infancy, Internet-based diabetes management shows great promise for growth. However, the following aspects must be considered: what are the key metrics for the evaluation of a diabetes-management site? how should these sites grow in the future and what services should they offer? OBJECTIVES: The purpose of this paper is to examine the needs of the patient and the health care professional in an Internet-based diabetes-management solution and how these needs are translated into services offered. METHODS: An evaluation framework was constructed based on a literature review that identified the requirements for an Internet-based-diabetes-management solution. The requirements were grouped into 5 categories: Monitoring, Information, Personalization, Communication, and Technology. Two of the market leaders (myDiabetes and LifeMasters) were selected and were evaluated with the framework. The Web sites were evaluated independently by 5 raters using the evaluation framework. All evaluations were performed from November 1, 2001 through December 15, 2001. RESULTS: The agreement level between raters ranged from 60% to 100%. The multi-rater reliability (kappa) was 0.75 for myDiabetes and 0.65 for LifeMasters, indicating substantial agreement. The results of the evaluations indicate that LifeMasters is a more-complete solution than myDiabetes in all dimensions except Information, where both sites were equivalent. LifeMasters satisfied 32 evaluation criteria while myDiabetes satisfied 24 evaluation criteria, out of a possible 40 in the framework. CONCLUSIONS: The framework is based on the recognition that the management of diabetes via the Internet is based on several integrated dimensions: Monitoring, Information, Personalization, Communication, and Technology. A successful diabetes-management system should efficiently integrate all dimensions. The evaluation found that LifeMasters is successful in integrating the health care professional in the management of diabetes and that MyDiabetes is quite effective in providing a communication channel for community creation (however, communication with the health care professional is lacking).