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Biomedical subjects

L Wood

Publications and source records attributed to L Wood.

At least 253 records · Page 14Linked to original sources
PubMedDate not supplied

Revitalizing the General Practice Research Database: plans, challenges, and opportunities.

The General Practice Research Database (GPRD) is the world's largest computerized database of anonymized longitudinal patient records from general practice and is a unique public health research tool. Several issues have threatened the viability of the database in recent years; in April 1999 responsibility for its management and financial control was transferred to the UK Medicines Control Agency (MCA). This presentation outlines the MCA's plans and future vision for the GPRD.

Data Collection↗
PubMedDate not supplied

Regulation of IL-5 and IL-5 receptor expression in the bone marrow of allergic asthmatics.

BACKGROUND: Following consistent demonstrations of the clinical relevance of fluctuations in eosinophil-basophil (Eo-B) progenitors in the blood of patients with a variety of allergic airway disorders, we have turned our attention recently to hemopoietic events occurring in the bone marrow of allergic asthmatic subjects, utilizing a model of airway allergen challenge. METHODS: Flow-cytometric analyses of CD34/45+ progenitors for coexpression of surface alpha-receptor subunits for IL-3, IL-5 and GM-CSF, as well as in situ hybridization and in situ PCR methodologies to detect mRNA for IL-5 and GM-CSF in developing Eo-B in colony and liquid culture assays were employed before and after in vivo allergen challenge. RESULTS: An early, specific upregulation of IL-5R alpha expression on CD34/45 progenitors was observed after allergen challenge, concomitant with the development of the late-phase asthmatic response. Protein and mRNA for both GM-CSF and IL-5 were expressed in a time-dependent manner ex vivo, in developing (beta 7-integrin-positive), colony-derived Eo-B after allergen challenge in vivo. Both retinoic acid and corticosteroids were able to downregulate IL-3- and IL-5-induced expression of IL-5R on cord-blood-derived as well as HL-60 cloned Eo-B progenitors. CONCLUSION: These studies indicate the critical involvement of IL-5 and IL-5R in the induction of Eo-B differentiation and eosinophilic airway inflammation in allergic asthmatics, and point to these events as potential targets for long-term therapy of atopic disease.

Asthma↗
PubMedDate not supplied

The use of multivariate methods in the identification of subtypes of Alzheimer's disease: a comparison of principal components and cluster analysis.

Two contrasting multivariate statistical methods, viz., principal components analysis (PCA) and cluster analysis were applied to the study of neuropathological variations between cases of Alzheimer's disease (AD). To compare the two methods, 78 cases of AD were analyzed, each characterised by measurements of 47 neuropathological variables. Both methods of analysis revealed significant variations between AD cases. These variations were related primarily to differences in the distribution and abundance of senile plaques (SP) and neurofibrillary tangles (NFT) in the brain. Cluster analysis classified the majority of AD cases into five groups which could represent subtypes of AD. However, PCA suggested that variation between cases was more continuous with no distinct subtypes. Hence, PCA may be a more appropriate method than cluster analysis in the study of neuropathological variations between AD cases.

Aged↗
PubMedDate not supplied

Bone marrow progenitors in allergic airways diseases: studies in canine and human models.

In a canine model of Ascaris suum-inducible bronchial hyperresponsiveness, we previously demonstrated that bone marrow-derived myeloid progenitors rise within 24 h of allergen inhalation; this effect is abolished by pretreatment with inhaled budesonide. We now report that this allergen-induced bone marrow response is observable in human asthmatics, and involves increases in both neutrophil-macrophage and eosinophil-basophil progenitors, within 6 h of allergen inhalation, as measured either by hematopoietic colony assays or by flow cytometric analyses of CD34+, IL-3R alpha+, and/or IL-5-responsive cell populations. In dogs, but not in humans, a transferrable serum hematopoietic activity accounts for the marrow response to inhaled allergen. These findings suggest that allergen-induced increases in bone marrow progenitor formation depend either on a serum hematopoietic factor(s) released after allergen challenge, or upon constitutive marrow upregulation of specific progenitors in allergic airway disease. Further studies to characterize the serum hematopoietic factor(s) and to determine the nature of any atopy-related progenitor profile are in progress.

Animals↗
PubMedDate not supplied

Serum antibody response induced in mice after oral administration of three different antigens of enterotoxigenic Escherichia coli in enteric coated microparticles.

BACKGROUND: Gastric digestion of these antigens plays an important role, decreasing the ability to deliver antigens to the gut-associated lymphoid tissue. To overcome this obstacle, microencapsulated antigens from enterotoxigenic Escherichia coli (ETEC) were evaluated for oral immunization of mice. METHODS: Four groups of 10 each received 3 series of 3 doses each of (1) B subunit of cholera toxin (CTB), similar to heat-labile toxin of ETEC, (2) formalin-killed whole cell ETEC H10407 (FK-ETEC), (3) crude preparation of colonization factor antigen I (CFA/I), or (4) placebo. Serum antibody was measured on day 0 and 60 by ELISA. RESULTS: In group 1 a CTB antibody response was induced in all mice, 3 with 1:105 titer and 7 with 1:106. These antibodies neutralized cholera toxin-induced steriodogenesis of Y-1 adrenal cells. In group 2, 8 mice developed a whole H10407 bacteria antibody titer of 1:100, one 1:200 and one showed no immune response. In the same group, an anti-CFA/I response was observed in 6 mice and anti-LPS in 4 mice as determined by Western blot. All mice in group 3 showed > 1:104 anti-CFA/I antibody titer. Group 4 mice did not develop an immune response to any ETEC antigens. CONCLUSIONS: Microencapsulation appears to be a suitable approach for oral vaccination against ETEC and Vibrio cholerae.

Animals↗