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Biomedical subjects

M A Brown

Publications and source records attributed to M A Brown.

At least 91 records · Page 5Linked to original sources
PubMed2000

Breath-hold 3D gradient-echo MR imaging of the lung parenchyma: evaluation of reproducibility of image quality in normals and preliminary observations in patients with disease.

This study evaluates the reproducibility and image quality of a three-dimensional (3D) gradient-echo sequence for imaging the lung parenchyma, with and without gadolinium administration, using a 2D spoiled gradient-echo sequence for comparison. Twenty patients without lung disease (normals) and five patients with lung disease (lung disease) underwent paired 2D and 3D gradient-echo sequences, without contrast (24 patients) and with contrast (18 patients). Images were retrospectively reviewed independently in a blinded fashion by two investigators. Artifacts and demonstration of central lung, peripheral lung, heart, pulmonary arteries, and esophagus were evaluated. Image quality of the central lung was rated as fair or good in 5 and 4 (reader one and two) patients with non-contrast 2D gradient-echo, 24 and 25 patients with non-contrast 3D gradient-echo, 3 and 1 patient(s) with contrast-enhanced 2D gradient-echo, and 19 and 19 patients with contrast-enhanced 3D gradient-echo imaging. Differences in image quality between 2D and 3D sequences were significant (P < 0.001). Heart-related phase artifacts were negligible in 2 and 0 patients with non-contrast 2D gradient-echo, 23 and 25 patients with non-contrast 3D gradient-echo, 0 and 0 patients with contrast-enhanced 2D gradient-echo, and 17 and 19 patients with contrast-enhanced 3D gradient-echo imaging. Differences in heart-related phase artifact in the central lung between 2D and 3D sequences were significant (P = 0.001). Infiltrates, lung cancer, and pulmonary metastasis were better shown on the gadolinium-enhanced 3D gradient-echo sequences than on the other sequences. Breath-hold 3D gradient-echo imaging results in good image quality and negligible image artifacts and is superior to 2D spoiled gradient-echo imaging. Preliminary results in patients with disease appear promising.

Artifacts↗
PubMed2000

The X-chromosome and susceptibility to ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) affects 0.25-1.0% of the population, and its etiology is incompletely understood. Susceptibility to this highly familial disease (lambda(s) = 58) is primarily genetically determined. There is a significant sex bias in AS, and there are differences in recurrence risk to the offspring of affected mothers and fathers, suggesting that there may be an X-linked recessive effect. We undertook an X-chromosome linkage study to determine any contribution of the X-chromosome to AS susceptibility. METHODS: A linkage study of the X-chromosome using 234 affected sibling pairs was performed to investigate this hypothesis. RESULTS: No linkage of the X-chromosome with susceptibility to AS was found. Model-free multipoint linkage analysis strongly excluded any significant genetic contribution (lambda > or = 1.5) to AS susceptibility encoded on the X-chromosome (logarithm of odds [LOD] <-2.0). Smaller genetic effects (lambda > or = 1.3) were also found to be unlikely (LOD <-1.0). CONCLUSION: The sex bias in AS is not explained by X-chromosome-encoded genetic effects. The disease model best explaining the sex bias in occurrence and transmission of AS is a polygenic model with a higher susceptibility threshold in females.

Genetic Linkage↗
PubMed2000

Diet composition and insulin action in animal models.

Critical insights into the etiology of insulin resistance have been gained by the use of animal models where insulin action has been modulated by strictly controlled dietary interventions not possible in human studies. Overall, the literature has moved from a focus on macronutrient proportions to understanding the unique effects of individual subtypes of fats, carbohydrates and proteins. Substantial evidence has now accumulated for a major role of dietary fat subtypes in insulin action. Intake of saturated fats is strongly linked to development of obesity and insulin resistance, while that of polyunsaturated fats (PUFAs) is not. This is consistent with observations that saturated fats are poorly oxidized for energy and thus readily stored, are poorly mobilized by lipolytic stimuli, impair membrane function, and increase the expression of genes associated with adipocyte profileration (making their own home). PUFAs have contrasting effects in each instance. It is therefore not surprising that increased PUFA intake in animal models is associated with improved insulin action and reduced adiposity. Less information is available for carbohydrate subtypes. Early work clearly demonstrated that diets high in simple sugars (in particular fructose) led to insulin resistance. However, again attention has rightly shifted to the very interesting issue of subtypes of complex carbohydrates. While no differences in insulin action have yet been shown, differences in substrate flux suggest there could be long-term beneficial effects on the fat balance of diets enhanced in slowly digested/resistant starches. A new area of major interest is in protein subtypes. Recent results have shown that rats fed high-fat diets where the protein component was from casein or soy were insulin-resistant, but when the protein source was from cod they were not. These are exciting times in our growing understanding of dietary factors and insulin action. While it has been clear for some time that 'oils ain't oils', the same is now proving true for carbohydrates and proteins.

Animals↗
PubMed2000

Interethnic studies of TNF polymorphisms confirm the likely presence of a second MHC susceptibility locus in ankylosing spondylitis.

The objective of this study was to investigate TNF promoter region polymorphisms for association with susceptibility to ankylosing spondylitis (AS). The TNF -238 and -308 polymorphisms were genotyped in 306 English AS cases and 204 ethnically matched healthy B27-positive controls, and 96 southern German AS cases, 58 B27-positive and 251 B27-negative ethnically matched controls. Additionally, the TNF -376 polymorphism was genotyped in the southern German cases and controls. In the southern German AS patients a significant reduction in TNF -308.2 alleles was seen, compared with B27 positive controls (odds ratio 0.4, P = 0.03, 95% confidence interval 0.2-0.9), but no difference in allele frequencies was observed at TNF -238. Significant association between AS and both TNF -238 and TNF -308 was excluded in the English cases. These results confirm previous observations in the southern German population of association between TNF promoter region polymorphisms and AS, but the lack of association in the English population suggests that these polymorphisms themselves are unlikely to be directly involved. More likely, a second, non-HLA-B, MHC locus is involved in susceptibility to AS in these two populations.

Alleles↗
PubMed2000

Relationships between perception of engagement with health care provider and demographic characteristics, health status, and adherence to therapeutic regimen in persons with HIV/AIDS.

The purpose of this descriptive, correlational study was to examine the relationships between perception of engagement with health care provider and demographic characteristics, health status, and adherence to therapeutic regimen in persons with HIV/AIDS. The convenience sample of 707 non-hospitalized persons receiving health care for HIV/AIDS was recruited from seven U.S. sites. All measures were self-report. Perception of engagement with health care provider was measured by the newly developed Engagement with Health Care Provider scale. Adherence to therapeutic regimen included adherence to medications, provider advice, and appointments. Health status was measured by the Medical Outcomes Study Short Form 36 (MOS SF-36), Living with HIV scale, CD4 count, and length of time known to be HIV-positive. There were no significant relationships between engagement with health care provider and age, gender, ethnicity, and type of health care provider. Subscales of the MOS SF-36 and Living with HIV explained a significant, but modest amount of the variance in engagement. Clients who were more engaged with their health care provider reported greater adherence to medication regimen and provider advice. Clients who missed at least one appointment in the last month or who reported current or past injection drug use were significantly less engaged.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Surviving the proving ground: lessons in change from NP pioneers.

Increasing competition, health care complexity, threats to quality, and rapidly changing environments confront nurse practitioners (NPs) as they enter the new millennium. If NPs are to strengthen their positions as health care providers and continue to make a lasting contribution, they must exhibit proficiency in creating and managing change. Lessons gleaned from those who pioneered the NP role can provide the wisdom needed to address contemporary role challenges. The purpose of this study was to identify the strategies employed by NP pioneers who contributed to role survival and growth. This article provides a discussion of the change strategies utilized by NP pioneers and highlights their relevance to current practice issues.

Adaptation, Psychological↗
PubMed2000

Recurrence risk modelling of the genetic susceptibility to ankylosing spondylitis.

OBJECTIVES: It has long been suspected that susceptibility to ankylosing spondylitis (AS) is influenced by genes lying distant to the major histocompatibility complex. This study compares genetic models of AS to assess the most likely mode of inheritance, using recurrence risk ratios in relatives of affected subjects. METHODS: Recurrence risk ratios in different degrees of relatives were determined using published data from studies specifically designed to address the question. The methods of Risch were used to determine the expected recurrence risk ratios in different degrees of relatives, assuming equal first degree relative recurrence risk between models. Goodness of fit was determined by chi(2) comparison of the expected number of affected subjects with the observed number, given equal numbers of each type of relative studied. RESULTS: The recurrence risks in different degrees of relatives were: monozygotic (MZ) twins 63% (17/27), first degree relatives 8.2% (441/5390), second degree relatives 1.0% (8/834), and third degree relatives 0. 7% (7/997). Parent-child recurrence risk (7.9%, 37/466) was not significantly different from the sibling recurrence risk (8.2%, 404/4924), excluding a significant dominance genetic component to susceptibility. Poor fitting models included single gene, genetic heterogeneity, additive, two locus multiplicative, and one locus and residual polygenes (chi(2) >32 (two degrees of freedom), p<10(-6) for all models). The best fitting model studied was a five locus model with multiplicative interaction between loci (chi(2)=1.4 (two degrees of freedom), p=0.5). Oligogenic multiplicative models were the best fitting over a range of population prevalences and first degree recurrence risk rates. CONCLUSIONS: This study suggests that of the genetic models tested, the most likely model operating in AS is an oligogenic model with predominantly multiplicative interaction between loci.

Female↗
PubMed2000

Attitudes about antidepressants: influence of information about weight-related side effects.

Antidepressant drugs are frequently prescribed for women and have various side effects, including potential effects on body weight. This experiment examined the effects of information about the weight-related side effects of antidepressants on women's attitudes toward the drugs. 60 college women were randomly assigned to read about one of two drugs, fluoxetine (Prozac) or imipramine (Tofranil). Participants were either told or not told about veridical weight-related side effects, namely, weight loss for Prozac and weight gain for Tofranil. As hypothesized, weight-gain information lowered the personal acceptability of Tofranil, and weight-loss information enhanced the acceptability of Prozac. Although research with clinical populations is required, undergraduate women's decisions about the use of antidepressant medications may be influenced by societal body-image ideals.

Adolescent↗
PubMed2000

Genotype x environment interactions in Angus, Brahman, and reciprocal-cross cows and their calves grazing common bermudagrass, endophyte-infected tall fescue pastures, or both forages.

Reproductive and preweaning data on 190 Angus (A x A), Brahman (B x B), and reciprocal-cross cows (A x B and B x A) and 434 two- and three-breed-cross calves managed on common bermudagrass (BG), endophyte-infected tall fescue (E+), or a combination of both forages (ROT) were used to evaluate the interaction of forage type with individual and maternal heterosis and maternal and grandmaternal breed effects. Cows were born from 1988 to 1991, and calves sired by 13 Polled Hereford bulls were born from 1995 to 1997. Heterosis for calving rate was larger on E+ than on BG or ROT (P < .05), whereas maternal effects were larger on BG than on ROT (P < .10). Maternal heterosis for birth weight was negative on BG (P < .11) but positive on E+ and ROT (P < .10). Grandmaternal effects were evident on BG (P < .10) and E+ (P < .01) but not on ROT. Forage effects were generally substantial for 205-d weight, calf weaning hip height, and calf weaning weight:height ratio; BG was highest, ROT was intermediate, and E+ was lowest. Maternal heterosis for these traits was generally greater on E+ than on BG (P < .10). Grandmaternal effects for 205-d weight, hip height, and weight:height ratio were not important on any forage. Heterosis for weaning weight per cow exposed was substantial on all forages (P < .01) and was significantly greater on E+ (P < .01) than on BG or ROT, but maternal effects were not significant. Thus, we observed more advantage to Brahman-cross cows over purebreds on E+ than on BG. We also observed that moving cows and calves from E+ to BG in the summer will alleviate some, but not all, of the deleterious effects of E+ on calf growth, although it may be more beneficial for reproductive traits in purebred cows.

Animal Feed↗
PubMed2000

The genetics of osteoporosis. Future diagnostic possibilities.

The risk of developing osteoporosis is determined by the interaction of several mostly unknown genes and environmental factors. Genetic studies in osteoporosis have largely focussed on association studies of a small number of candidate genes, with few linkage studies performed, and large areas of the genome remaining unexplored. Identifying the genes involved in osteoporosis would be a major advance in our understanding of the causation of the disease, and lead to advances in diagnosis, risk prediction, and potentially preventive and therapeutic measures.

Chromosome Mapping↗
PubMed1999

Genetic studies of osteoporosis.

Osteoporosis is a common condition of men and women, which is characterised by an increase in bone fragility due to a reduction in the amount of bone tissue. Predisposition to osteoporosis is largely genetically determined, and it is likely that several genes, each having a small effect, are involved. Bone density is determined by the peak bone mass achieved, and the rate and timing of subsequent bone loss. Twin and family studies suggest that the genetic determinants of bone density in later life influence predominantly, but not exclusively, peak bone mass. Although many genes influence bone density in both males and females, at different skeletal sites and in different age groups, it is likely that the magnitude of individual genetic effects differs in different population subsets and in different environmental settings. Thus, weak to moderate genetic effects might be identified only in specific subsets of the population. Rapid advances in the field of human genetics during the past decade have greatly improved our chances of successfully identifying genes that are involved in complex genetic conditions such as osteoporosis, and ultimately might lead to the development of new diagnostic and predictive tests as well as novel treatments for this condition. In this review, we have outlined the methods that are currently being employed to identify osteoporosis genes and also the progress that has been made to date in this field.

Journal Article↗
PubMed1999

Cutting edge: IL-4 production by mast cells does not require c-maf.

The c-maf transcription factor is selectively expressed in IL-4-producing Th2 cells. It has been implicated in IL-4 gene transcription based on its ability to directly activate the IL-4 gene in nonexpressing B cells and to promote IL-4-induced Th2 differentiation. However, it has not been definitively shown that IL-4 production by other cells is dependent on the presence of c-maf. Here, we show that IL-4-producing mast cells do not express the c-maf factor. Furthermore, mutation of a defined c-maf binding site within the proximal IL-4 promoter, which profoundly affects transcription in T cells, has no effect on expression of a reporter gene driven by the IL-4 promoter in mast cells. These results demonstrate that c-maf and its target binding site are not required for IL-4 production in all cell types and delineate additional cis- and trans-acting elements that contribute to the cell-type specific transcriptional regulation of IL-4.

Animals↗
PubMed1999

IL-4 preferentially activates a novel STAT6 isoform in mast cells.

IL-4 is a pleiotropic cytokine that signals through STAT6 to direct the transactivation of multiple gene targets. In this study, we demonstrate that mast cells express a distinct STAT6 isoform. This "mast cell STAT" is a product of the STAT6 gene, but is only 65 kDa in size and appears to lack the defined C-terminal transactivation domain. Despite the presence of the conventional 94-kDa STAT6 molecule, it is the smaller isoform that associates with a consensus STAT6 binding site in extracts from IL-4-treated mast cells. This is the first evidence that STAT6 isoforms can be preferentially activated and bind to DNA in a cell-specific manner. These results imply that an additional level of specificity in the IL-4R signaling mechanism exists and may partially explain the diverse effects that IL-4 exerts on different cell types.

Animals↗
PubMed1999

NF-ATc isoforms are differentially expressed and regulated in murine T and mast cells.

NF of activated T cells (NF-AT) denotes a family of transcription factors that regulate the activation-dependent expression of many immunologically important proteins. At least four distinct genes encode the various family members, and several isoforms of these have been identified as well. The overlapping expression patterns and similar in vitro binding and trans-activation activities on various promoter elements of NF-AT-regulated genes suggest some redundancy in the function of these proteins. However, the phenotypic analysis of NF-AT-deficient mice supports the idea that there are tissue- and gene-specific functions as well. In this study we have characterized the expression of NF-AT cDNAs in murine mast cells. The majority of clones identified correspond to two NF-ATc isoforms that differ only in their amino-terminal sequence. Despite minimal discrepancies in the coding region, there are striking tissue- and cell type-specific differences in isoform expression patterns. Detection of NF-ATc.alpha mRNA is strictly dependent on cell activation signals in both T and mast cell lines. In contrast, the beta isoform is expressed at very low constitutive levels in both cell types but is only up-regulated in response to mast cell activation signals delivered through the FcepsilonRI or via calcium ionophores. These results demonstrate another level of regulation within the NF-AT family that can contribute to cell type-specific gene expression.

Amino Acid Sequence↗
PubMed1999

STAT6-independent production of IL-4 by mast cells.

The acquisition of an IL-4-producing phenotype in Th2 cells requires IL-4 signaling through the STAT6 pathway during T cell differentiation. In this study we demonstrate that, unlike in naive T cells, IL-4 is not necessary for the development of an IL-4-producing phenotype in mast cells. Bone marrow-derived mast cell precursors from STAT6-/- mice can differentiate into mature cells that express IL-4 levels comparable to those of wild-type mast cells. In differentiated mast cells, activation in the presence of neutralizing anti-IL-4 antibodies or mutation of the consensus STAT6 sites does not diminish IL-4 promoter activity, indicating that IL-4 is not required for active transcription. Taken together, these data suggest that mast cell IL-4 production is not STAT6 dependent, providing evidence that these cells could generate IL-4 needed for the initiation and amplification of an effective Th2 immune response.

Animals↗