Biomedical subjects

Lisa Martin

Publications and source records attributed to Lisa Martin.

13 recordsLinked to original sources

PubMed2006

Development of autoimmunity in IL-14alpha-transgenic mice.

Multiple genetic loci contribute to the development of systemic lupus erythematosus (SLE). In murine models for SLE, various genes on chromosome four have been implicated. IL-14 is a cytokine originally identified as a B cell growth factor. The il14 gene is located on chromosome 4. IL-14alpha is a cytokine encoded by the plus strand of the IL-14 gene using exons 3-10. The expression of IL-14alpha is increased in (NZB x NZW)F1 mice. In this study, we produced IL-14alpha-transgenic mice to study the role of IL-14alpha in the development of autoimmunity. At age 3-9 mo, IL-14alpha-transgenic mice demonstrate increased numbers of B1 cells in the peritoneum, increased serum IgM, IgG, and IgG 2a and show enhanced responses to T-dependent and T-independent Ags compared with littermate controls. At age 9-17 mo, IL-14alpha-transgenic mice develop autoantibodies, sialadenitis, as in Sjögren's syndrome, and immune complex-mediated nephritis, as in World Health Organization class II SLE nephritis. Between the ages 14-18 mo, 95% of IL-14alpha-transgenic mice developed CD5+ B cell lymphomas, consistent with the lymphomas seen in elderly patients with Sjögren's syndrome and SLE. These data support a role for IL-14alpha in the development of both autoimmunity and lymphomagenesis. These studies may provide a genetic link between these often related disorders.

Age Factors↗

PubMed2006

Dietary patterns in patients with advanced cancer: implications for anorexia-cachexia therapy.

BACKGROUND: Severe malnutrition and wasting are considered hallmarks of advanced malignant disease, and clinical research into anorexia-cachexia therapy and nutritional support for cancer patients is ongoing. However, information on typical dietary intakes and food choices for this population is notably lacking; proposed therapies for anorexia and wasting are not framed within the context of current intake. OBJECTIVE: The objective of the study was to characterize the food intake patterns of patients with advanced cancer. DESIGN: Patients with advanced cancer (n = 151) recruited from a regional cancer center and palliative-care program completed a 3-d dietary record a mean (+/-SD) 8 +/- 7 mo before death. Food items were categorized according to macronutrient content and dietary use and subsequently entered into cluster analysis. RESULTS: Wide variations in intakes of energy (range: 4-53 kcal . kg body wt(-1) . d(-1); x +/- SD: 25.1 +/- 10.0 kcal . kg body wt(-1) . d(-1)) and protein (range: 0.2-2.7 g . kg body wt(-1) . d(-1); x +/- SD: 1.0 +/- 0.4 g . kg body wt(-1) . d(-1)) were observed. Even the subjects with the highest intakes had a recent history of weight loss, which suggests that the diets of those persons were consistently inadequate for weight maintenance. Cluster analysis found 3 dietary patterns that differed in food choice and caloric intake. Low intakes and a high risk of weight loss were associated with decreased frequency of eating and dietary profiles with little variety and unusually high proportions of liquids. CONCLUSION: These data provide a glimpse into dietary habits toward the end of life. Unique dietary patterns were found in this nutritionally vulnerable patient population.

Aged↗

PubMed2006

Cohesive short-stretch vs four-layer bandages for venous leg ulcers.

Nurses today are employing more and more evidence base within their practice. This must be carefully balanced with their ability to offer patients choice about treatment options for venous leg ulceration. Knowledge of only one particular compression bandage system is inadequate for nurses working within this area. This article aims to examine the evidence base for the use of compression bandaging in the treatment of leg ulceration. It explores results of current randomised controlled trials in this area pertaining to four-later bandage (4LB) and cohesive short-stretch bandage (CSSB) systems. The advantages and disadvantages of the 4LB and CSSB are explored and application method of CSSB is explained. Concordance is and important issue that affects successful leg ulcer management (Moffatt, 2004a): if this can be achieved through offering patients choice of treatment bandages, then more successful treatment will be achieved for patients.

Bandages↗

PubMed2005

Forced expression of alpha-myosin heavy chain in the rabbit ventricle results in cardioprotection under cardiomyopathic conditions.

BACKGROUND: The biochemical differences between the 2 mammalian cardiac myosin heavy chains (MHCs), alpha-MHC and beta-MHC, are well described, but the physiological consequences of basal isoform expression and isoform shifts in response to altered cardiac load are not clearly understood. Mature human ventricle contains primarily the beta-MHC isoform. However, the alpha-MHC isoform can be detected in healthy human ventricle and appears to be significantly downregulated in failing hearts. The unique biochemical properties of the alpha-MHC isoform might offer functional advantages in a failing heart that is expressing only the beta-MHC isoform. This hypothesis cannot be tested in mice or rats because both species express alpha-MHC as the predominant isoform. METHODS AND RESULTS: To test the effects of persistent alpha-MHC expression on the background of beta-MHC, we made transgenic (TG) rabbits that expressed rabbit alpha-MHC cDNA in the ventricle so that the endogenous myosin was partially replaced by the transgenically encoded species. Molecular, histological, and functional analyses showed no significant baseline effects in the TG rabbits compared with nontransgenic (NTG) littermates. To determine whether alpha-MHC expression afforded any advantages to stressed myocardium, a cohort of TG and NTG rabbits was subjected to rapid ventricular pacing. Although both the TG and NTG rabbits developed dilated cardiomyopathy, the TG rabbits had a higher shortening fraction, less septal thinning, and more normal +/-dP/dt than paced NTG rabbits. CONCLUSIONS: Transgenic expression of alpha-MHC does not have any apparent detrimental effects under basal conditions and is cardioprotective in experimental tachycardia-induced cardiomyopathy.

Animals↗

PubMed2005

Transgenic rabbit model for human troponin I-based hypertrophic cardiomyopathy.

BACKGROUND: Transgenic and gene-targeted models have focused on the mouse. Fundamental differences between the mouse and human exist in Ca2+ handling during contraction/relaxation and in alterations in Ca2+ flux during heart failure, with the rabbit more accurately reflecting the human system. METHODS AND RESULTS: Cardiac troponin I (cTnI) mutations can cause familial hypertrophic cardiomyopathy. An inhibitory domain mutation, arginine146-->glycine (cTnI(146Gly)), was modeled with the use of transgenic expression in the rabbit ventricle. cTnI(146Gly) levels >40% of total cTnI were perinatally lethal, whereas replacement levels of 15% to 25% were well tolerated. cTnI(146Gly) expression led to a leftward shift in the force-pCa2+ curves with cardiomyocyte disarray, fibrosis, and altered connexin43 organization. In isolated cTnI(146Gly) myocytes, twitch relaxation amplitudes were smaller than in normal cells, but [Ca]i transients and sarcoplasmic reticulum Ca2+ load were not different. Detrended fluctuation analysis of the QT(max) intervals was used to evaluate the cardiac repolarization phase and showed a significantly higher scaling exponent in the transgenic animals. CONCLUSIONS: Expression of modest amounts of cTnI(146Gly) led to subtle defects without severely affecting cardiac function. Aberrant connexin organization, subtle morphological deficits, and an altered fractal pattern of the repolarization phase of transgenic rabbits, in the absence of entropy or other ECG abnormalities, may indicate an early developing pathology before the onset of more obvious repolarization abnormalities or major alterations in cardiac mechanics.

Animals↗

PubMed2005

High rates of uninsured among HCV-positive individuals.

BACKGROUND AND GOALS: There are no published data on the health insurance status of Hepatitis C virus (HCV)-positive individuals. To address this issue, we analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III). STUDY: Individuals 18 years of age and older who participated in NHANES III were included in the study. We determined the rates of health insurance coverage according to HCV status. We also determined healthcare status and health service utilization according to health insurance status among HCV-positive persons. RESULTS: HCV-positive individuals were more likely to be uninsured compared with those who were HCV-negative (29.6% vs. 12.2%, P = 0.0002). Among those with health insurance, HCV-positive individuals were more likely to have government insurance compared with those who were HCV-negative (42.9% vs. 27.6%, P < 0.005). Among HCV-positive individuals, being uninsured was associated with younger age, being unmarried, living in the South, Mexican-American race/ethnicity, and not graduating from high school. Additionally, the uninsured were less likely than their insured counterparts to identify a healthcare facility for sick or routine care, and less likely to have regular contact with a healthcare professional. CONCLUSIONS: A high proportion of HCV-positive individuals are uninsured, and many HCV-positive individuals with health insurance have publicly funded insurance. This finding may have implications for access to health care and for liver-related disease outcomes in HCV-positive persons.

Adolescent↗

PubMed2005

The association of measured breast tissue characteristics with mammographic density and other risk factors for breast cancer.

BACKGROUND: We have examined the relationships between the measured properties of breast tissue and mammographic density and other risk factors for breast cancer, using breast tissue obtained at forensic autopsy and not selected for the presence of abnormalities. METHODS: We used randomly selected tissue blocks taken from breast tissue slices obtained by s.c. mastectomy at the time of forensic autopsy to measure histologic features using quantitative microscopy. The proportions of the biopsy occupied by cells (estimated by nuclear area), glandular structures, and collagen were determined. These measurements were examined in relation to the percent density in the faxitron image of the tissue slice from which the biopsy was taken and other risk factors for breast cancer. RESULTS: The percent mammographic density was associated with the proportion of the area of the biopsy occupied by nuclei, both epithelial and nonepithelial, and by collagen and the area of glandular structures. Several other risk factors for breast cancer, notably body weight, parity, and number of births, and menopausal status, that are associated with variations in mammographic density, were also associated with differences in one or more of these tissue features. CONCLUSION: All risk factors for breast cancer must ultimately exert their influence by an effect on the breast, and these findings suggest that, for some risk factors, this influence includes an effect on the number of cells and the quantity of collagen.

Adolescent↗

PubMed2004

Cytochrome P450 1A2 (CYP1A2) activity, mammographic density, and oxidative stress: a cross-sectional study.

INTRODUCTION: Mammographically dense breast tissue is a strong predictor of breast cancer risk, and is influenced by both mitogens and mutagens. One enzyme that is able to affect both the mitogenic and mutagenic characteristics of estrogens is cytochrome P450 1A2 (CYP1A2), which is principally responsible for the metabolism of 17beta-estradiol. METHODS: In a cross-sectional study of 146 premenopausal and 149 postmenopausal women, we examined the relationships between CYP1A2 activity, malondialdehyde (MDA) levels, and mammographic density. In vivo CYP1A2 activity was assessed by measuring caffeine metabolites in urine. Levels of serum and urinary MDA, and MDA-deoxyguanosine adducts in DNA were measured. Mammograms were digitized and measured using a computer-assisted method. RESULTS: CYP1A2 activity in postmenopausal women, but not in premenopausal women, was positively associated with mammographic density, suggesting that increased CYP1A2 activity after the menopause is a risk factor for breast cancer. In premenopausal women, but not in postmenopausal women, CYP1A2 activity was positively associated with serum and urinary MDA levels; there was also some evidence that CYP1A2 activity was more positively associated with percentage breast density when MDA levels were high, and more negatively associated with percentage breast density when MDA levels were low. CONCLUSION: These findings provide further evidence that variation in the activity level of enzymes involved in estrogen metabolism is related to levels of mammographic density and potentially to breast cancer risk.

Adult↗

PubMed2004

Risk factors for breast cancer associated with mammographic features in Singaporean chinese women.

BACKGROUND: Mammographic density has been found to be a strong risk factor for breast cancer and to be associated with age, body weight, parity, and menopausal status. Most studies to date have been carried out in Western populations. The purpose of the study described here was to determine in a cross-sectional study in a Singaporean Chinese population the demographic, menstrual, reproductive, and anthropometric factors that are associated with quantitative variations in age-adjusted percentage mammographic densities and to examine the association of these factors with the dense and nondense areas of the mammogram. METHOD: We used mammograms and questionnaire data collected from subjects in the Singapore Breast Screening Project. Women ages 45 to 69 years participated and 84% of those screened were Chinese. Mammograms were digitized and percentage density was measured and analyzed in relation to the questionnaire data. RESULTS: Percentage mammographic density was associated with several risk factors for breast cancer, most of them also associated, in opposite directions, with the dense and nondense components of the image. Percentage density was associated with age and weight (both negatively), height and age at first birth (both positively), and number of births and postmenopausal status (both negatively). Percentage density was weakly associated with a previous breast biopsy but was not associated with age at menarche or menopause, with use of hormones, or with a family history of breast cancer. CONCLUSION: Percentage mammographic density in Singaporean Chinese women has similar associations with risk factors for breast cancer to those seen in Caucasians.

Aged↗

PubMed2003

The baboon as a nonhuman primate model for the study of the genetics of obesity.

OBJECTIVE: At present, rodents represent the most common animal model for research in obesity and its comorbidities (e.g., type 2 diabetes and coronary heart disease), however, there are several physiological and developmental differences between rodents and humans reflective of their relatively ancient evolutionary divergence (approximately 65 to 75 million years ago). Therefore, we are currently developing the baboon as a nonhuman primate model for the study of the genetics of obesity. RESEARCH METHODS AND PROCEDURES: At present, we are collecting extensive phenotypic data in a large pedigreed colony (N > 2000) of baboons housed at the Southwest Foundation for Biomedical Research in San Antonio, Texas. The long-term goal of this project is to identify genes influencing adiposity-related phenotypes and to test hypotheses regarding their pleiotropic effects on other phenotypes related to increased risk for a variety of common diseases (e.g., coronary heart disease and type 2 diabetes). RESULTS: To date we have obtained various adipose-specific endocrine measures, adipose tissue biopsies, and estimates of body composition on a substantial portion of our pedigreed colony. The pattern of adipose tissue accumulation follows closely that seen in humans, and we have detected significant additive genetic heritabilities for these obesity-related phenotypes. DISCUSSION: Given the physiological and developmental similarities between humans and baboons, along with the ability to collect data under well-controlled situations and the extensive pedigree data available in our colony, the baboon offers an extremely valuable nonhuman primate model for the study of obesity and its comorbidities.

Adipose Tissue↗

PubMed2002

Transgenic rabbits expressing mutant essential light chain do not develop hypertrophic cardiomyopathy.

Mutations in multiple sarcomeric proteins can cause familial hypertrophic cardiomyopathy. Although a M149V mutation in the myosin light chain is associated with the human disease, the data from transgenic (TG) mouse models are conflicting. When a human genomic fragment containing the M149V essential myosin light chain was used to generate TG mice, the phenotype was recapitulated. However, when the mouse cDNA containing the mutation was used to generate TG animals, no phenotype could be discerned. TG rabbits can be a valuable complement and extension to mouse-based TG models and we wished to determine whether expression of this mutation in the rabbit heart would result in the disease. The rabbit essential light chain cDNA was isolated, sequenced, the M149V mutation made and the cDNA placed into the beta-myosin heavy chain promoter, which efficiently drives cardiac expression in the rabbit ventricles. Multiple TG rabbit lines showing different levels of protein replacement were obtained. No discernible pattern of disease was apparent at the structural or functional levels at either the neonatal, juvenile or adult stages. We conclude that the M149V mutation is not causative for FHC when expressed in the rabbit within the context of the endogenous protein.

Amino Acid Substitution↗

PubMed2002

Gallstones: genetics versus environment.

OBJECTIVE: The aim of this study was to determine if a significant genetic component contributes to the pathogenesis of symptomatic gallstones. SUMMARY BACKGROUND DATA: Gallstones represent a polygenic disorder that affects more than 30,000,000 Americans and results in more than 750,000 cholecystectomies in the United States annually. Risk factors include age, gender, race, parity, obesity, and diabetes. A family history of gallstones also has been identified as a risk factor suggesting that genetics play a role in gallstone formation. However, the role of genetics in the pathogenesis of gallstone formation has not been determined. METHODS: A gallbladder disease-specific questionnaire was administered to 904 healthy unrelated adult volunteers (association study). The questionnaire ascertained a history of cholecystectomy and gallstone disease in first-degree relatives, as well as medical history, demographic, and anthropometric data. A logistic regression model was used to identify risk factors for symptomatic gallstone disease in a multivariate analysis. A maximum likelihood based variance decomposition approach was then used in 1,038 individuals from 358 families (family study) to estimate the additive genetic heritability of symptomatic gallstone disease. RESULTS: In the association study significant risk factors for symptomatic gallstone disease were female gender (relative risk 8.8, P <.003), obesity (BMI > 30, relative risk 3.7, P <.001), age > 50 (relative risk 2.5, P <.001), and a positive family history of previous cholecystectomy in a first-degree family member (relative risk 2.2, P <.01). In the family study the additive genetic heritability of symptomatic gallstones was 29% (P <.02), age and gender were significant covariates and explained 9.3% of the phenotypic variation in gallbladder disease. CONCLUSIONS: These data suggest that genetic factors are responsible for at least 30% of symptomatic gallstone disease. However, the true role of heredity in gallstone pathogenesis is probably higher because data based on symptomatic gallbladder disease underestimates the true prevalence in the population.

Adolescent↗

PubMed2002

A longitudinal study of the effects of menopause on mammographic features.

Menopause has an important influence on risk of breast cancer. We have examined longitudinally the effect of menopause on mammographic densities, a strong risk factor for the disease, in women in the Canadian National Breast Screening Study. Baseline mammograms from women in the National Breast Screening Study, who were premenopausal at entry and had undergone menopause after entry, were compared with the mammogram that most closely followed menopause, using a computer-assisted method of measurement. The changes seen in the mammograms of these subjects were compared with those in an age-matched group of women who were also premenopausal at entry, had been followed for the same length of time, and had not experienced menopause. The results of this longitudinal study show that menopause has effects on characteristics of the mammogram that, over the same period of time, are greater than the effects of age. These effects are a reduction in the area of radiologically dense tissue, an increase in the area of nondense tissue, and a decrease in the percentage of density. However, these changes do not fully account for the effects of age on mammographic densities seen in cross-sectional data. Menopause is associated with distinct changes in the mammogram that account for some, but not all, of the observed association of increasing age with decreasing percentage of mammographic density. The observed changes in the morphology of the breast may explain some of the effect that menopause has on breast cancer risk.

Adult↗