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Biomedical subjects

M Perry

Publications and source records attributed to M Perry.

At least 37 records · Page 2Linked to original sources

Cytokine and endothelial cell adhesion molecule expression in interleukin-10-deficient mice.

The objectives of this study were to quantify cytokine mRNA levels and endothelial cell adhesion molecule message and protein expression in healthy wild-type and interleukin-10-deficient (IL-10(-/-)) mice that develop spontaneous and chronic colitis. We found that colonic message levels of IL-1, IL-6, tumor necrosis factor-alpha, interferon-gamma, lymphotoxin-beta, and transforming growth factor-beta were elevated in colitic mice 10- to 35-fold compared with their healthy wild-type controls. In addition, colonic message levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) were found to be increased 10-, 5-, and 23-fold, respectively, in colitic IL-10(-/-) mice compared with their wild-type controls. Immunoradiolabeling as well as immunohistochemistry revealed large and significant increases in vascular surface expression of colonic ICAM-1, VCAM-1, and MAdCAM-1 in the mucosa as well as the submucosa of the colons of colitic mice. These data are consistent with the hypothesis that deletion of IL-10 results in the sustained production of proinflammatory cytokines, leading to the upregulation of adhesion molecules and infiltration of mononuclear and polymorphonuclear leukocytes into the cecal and colonic interstitium.

Animals↗

Mutation detection in the breast cancer gene BRCA1 using the protein truncation test.

About 400 distinct mutations have been defined in the BRCA1 gene, and these are spread fairly evenly through the 5592 bp of coding DNA. This circumstance presents a formidable challenge for mutation screening. Apart from total direct sequencing, the preferred screening method has been single-strand conformation polymorphism (SSCP) gels, with a smaller input from constant denaturant gradient electrophoresis (CDGE), heteroduplex (HD) analysis, and mismatch cleavage. The protein truncation test (PTT) was used early in BRCA1 mutation screening but has not been widely adopted, perhaps because a straightforward analysis of the whole BRCA1 gene requires working with RNA and all its perceived problems. The present work was undertaken to assess the practicality of using the PTT under routine conditions for the screening of long genes such as BRCA1 that are not highly expressed in lymphocytes. We conclude that, provided RNA preparation is carried out effectively and consistently, the PTT approach has significant advantages over other methodologies such as SSCP gels.

Base Sequence↗

Identification of risk factors in hypertensive patients: contribution of randomized controlled trials through an individual patient database.

BACKGROUND: Predicting individual risk is needed to target preventive interventions toward people with the highest probability of benefit over a given time period. We assessed which prognostic factors should be used in predicting risk for hypertensive patients and in searching for treatment modifiers. METHODS AND RESULTS: Data from 24 390 hypertensive participants who constituted the control groups from 8 controlled trials (1726 deaths over 5 years) were analyzed in multivariate survival models. Outcomes were coronary heart disease death, stroke death, and cardiovascular death. We explored systematically the heterogeneity of results between trials. Left ventricular hypertrophy was electrocardiographically confirmed to be a powerful risk factor and should be included in risk scoring. Height, glomerular filtration rate, and serum uric acid deserve further exploration. Body mass index and heart rate were not confirmed as independent cardiovascular risk factors in this population. The association between male sex and coronary heart disease death was significantly stronger in British cohorts. The lack of prognostic value of diastolic blood pressure was explained by an interaction with age, with a positive association before 65 years and a negative association thereafter. Previous antihypertensive treatment was a significant risk factor. CONCLUSIONS: Clinical trials provide valuable information for risk prediction. Carefully exploring the heterogeneity among trials is a way to assess the generalizability of findings. This approach, if systematically performed, should increase the ability to identify risk modifiers and to predict individual therapeutic benefit.

Age Factors↗

Verbal imprecision as an index of knowledge in transition.

Children can be verbally imprecise when they are learning, but this phenomenon is not well documented. Verbal imprecision, anecdotally referred to as "hemming and hawing," may be indexed by restatements, comments on one's lack of knowledge, deletions of sentence constituents, and pauses. The authors examined whether they could quantify indexes of verbal imprecision and use them to predict changes in problem-solving performance. Four types of verbal imprecision were found to predict improved performance. Results were used to make inferences about processes of knowledge change. In particular, evidence suggests that adopting a new approach and rejecting an old one may be independent, and ordered, processes. Although others have drawn similar conclusions, using verbal imprecision as the data source is a relatively unique and readily accessible method for lending support to this model of knowledge change.

Child↗

B-cell antigens within normal and activated human T cells.

In this study we compared cell surface staining for human peripheral blood lymphocyte (PBL) CD antigens by flow cytometry, with staining obtained following permeabilization of PBL using the Cytoperm method (Serotec). Six CD antigens (CD20, CD21, CD22, CD32, CD35 and major histocompatibility complex class II antigen) normally found on the surface of B cells, were also found to be expressed within T cells. We also showed, by immunoelectron microscopy, that these inappropriately expressed ('occult') CD antigens are located within cytoplasmic vesicles or within the rough endoplasmic reticulum. Following in vitro activation of T cells a distinct increase in expression of all of these cytoplasmic antigens was observed but staining at the cell surface was, by comparison, weak. We therefore propose that up-regulation of various B-cell CD antigens occurs within the cytoplasm of T cells following activation and that these antigens may be synthesized and released into the fluid-phase as soluble immunoregulatory molecules.

Antigens, CD↗

Gene therapy for prostate cancer.

Prostate cancer is one of the leading causes of cancer deaths in the western hemisphere. A number of different gene therapy strategies are currently being evaluated. The ex vivo and many of the in vivo therapies involve stimulating a specific antitumor immune response. Autologous vaccines involving interleukin-2 (IL-2)- or granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced whole tumor cells showed great promise in animal models. Clinical trials of these and other vaccine strategies are underway. In vivo gene therapies involving the replacement of mutant tumor-suppressor genes, antisense strategies, and the insertion of suicide genes are also being evaluated in prostate cancer.

Antigens, Neoplasm↗

The use of computer-generated three-dimensional models in orbital reconstruction.

In this paper we describe the application of three-dimensional (3D) imaging and computer-generated models in the management of orbital deformity. The technique was found to be particularly useful in posttraumatic deformity and fibrous dysplasia involving the orbit. Further application was found in cases of radiation hypoplasia, high facial cleft, and facial atrophy. Funding restrictions necessitate appropriate selection of cases when using new and expensive 3D imaging rather than traditional and less expensive methods. To remain within a realistic budget only those patients who will clearly benefit from the third dimension compared with traditional methods of assessment and management should be selected. These include patients requiring precise reduction or secondary reconstruction in which there is a matched normal anatomical component for comparison. This application is also only beneficial where the planned reconstruction is dimensionally stable.

Adolescent↗

Use caution with serologic testing for Helicobacter pylori infection in children.

Commercial serologic assays accurately detect adult Helicobacter pylori infection. Their use in children remains controversial. An ELISA to detect H. pylori IgG in children was developed and compared with three commercial assays. ELISA standardization was done with sera from all ages and validation was done with another cohort of sera with known H. pylori status. Three commercial serologic assays were subsequently compared against this pediatric ELISA at independent sites, at which 142 pediatric serum samples from different countries were evaluated. The pediatric ELISA was 91.4% sensitive. Assay 3 demonstrated a sensitivity of 78%. Less sensitivity was observed for assay 1 (70%) and assay 2 (63%). Accuracy of commercial assays was greatly reduced when sera from developing countries and younger ages were evaluated. Results of serologic tests used to diagnose H. pylori should be interpreted with caution when evaluating children with abdominal pain. Accurate serologic assays in children may be more important for epidemiologic research than for clinical decision making.

Adolescent↗

COPD guidelines.

Explore the source record for details and available documents.

Cost-Benefit Analysis↗

ICAM-1 and P-selectin expression in a model of NSAID-induced gastropathy.

A growing body of experimental evidence suggests that neutrophilic polymorphonuclear leukocyte (PMN)-endothelial cell interactions play a critical role in the pathophysiology of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. The objective of this study was to directly determine whether the expression of endothelial cell adhesion molecules is enhanced in a model of NSAID-induced gastropathy. Gastropathy was induced in male Sprague-Dawley rats via oral administration of indomethacin (Indo, 20 mg/kg). Lesion scores, blood-to-lumen clearance of 51Cr-EDTA (mucosal permeability), and histological analysis (epithelial necrosis) were used as indexes of gastric mucosal injury. Gastric mucosal vascular expression of intercellular adhesion molecule 1 (ICAM-1) or P-selectin were determined at 1 and 3 h after Indo administration using the dual radiolabeled monoclonal antibody (MAb) technique. For some experiments, a blocking MAb directed at either ICAM-1 (1A29) or P-selectin (RMP-1) or their isotype-matched controls was injected intravenously 10 min before Indo administration. We found that P-selectin expression was significantly increased at 1 h but not 3 h after Indo administration, whereas ICAM-1 expression was significantly increased at both 1 and 3 h after Indo treatment. The blocking ICAM-1 and P-selectin MAbs both inhibited Indo-induced increases in lesion score, mucosal permeability, and epithelial cell necrosis. However, the Indo-induced gastropathy was not associated with significant PMN infiltration into the gastric mucosal interstitium, nor did Indo reduce gastric mucosal blood flow. We propose that NSAID-induced gastric mucosal injury may be related to the expression of P-selectin and ICAM-1; however, this mucosal injury does not appear to be dependent on the extravasation of inflammatory cells or mucosal ischemia.

Animals↗

The interdisciplinary team's approach to lupus nephritis.

The interdisciplinary team approach in assessment and treatment of patients with chronic disease in general and lupus nephritis in particular provides a global format for identifying the multiple problem areas that retard or prevent optimal patient functioning. These areas include the physical, emotional, economic, psychosocial, and functional. Benefits to the individual patient include a thorough multifaceted assessment by professionals who have the benefit of peer collaboration and validation. This increases the likelihood that the whole patient is considered, not just the problem of nephritis. For example, how does the patient and her or his family cope with the impact of such a disease and how, in turn, do the coping abilities of the patient and family affect the disease. The interdisciplinary team also assesses how the treatment strategies for each problem area influence each other. Finally, the interdisciplinary team serves as a positive role model for effective collaboration among health professionals and for students in their respective disciplines.

Adult↗