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TITLE: Alcohol, ERT and Cognition in Menopausal Women
INSTITUTE: NIAAA
P.I.: Dr. Laura Tivis
INSTITUTION: Oklahoma Center for Alcohol/Drug Studies
GRANT NO.: 1 R29 AA11172 01A1
KEYWORDS: substance abuse, alcohol, estrogen replacement therapy (ERT), exogenous estrogen, cognition, clinical
STUDY POP.: Postmenopausal Women
A large proportion of postmenopausal women are at least moderate consumers of alcohol. Little is known of the independent and potentially interactive effects of alcohol and exogenous estrogen on cognitive functioning and psychosocial characteristics. This study will determine whether drinking or use of estrogen replacement therapy (ERT), either independently or together, affect cognition in postmenopausal women. Potential relationships between estrogen levels, alcohol consumption and cognitive performance will be explored. The effect of progestin replacement therapy on cognition will also be explored. Amount funded: $87,500.
TITLE: Effects of Alcohol on Human Lactation and Infant Behavior
INSTITUTE: NIAAA
P.I.: Dr. Julie Mennella
INSTITUTION: Monnell Chemical Senses Center
GRANT NO.: 2 R01 AA09523 A1
KEYWORDS: alcohol, lactation, lactation abstinence, clinical
STUDY POP.: Women
This project will research the effects of moderate, socially acceptable alcohol consumption on maternal lactation performance. The information accrued will impact on a woman's decision to abstain from alcohol while lactating. Amount funded: $87,500.
TITLE: Alcohol Use During Pregnancy – Public Education Campaign
INSTITUTE: NIAAA
P.I.: N/A
INSTITUTION: N/A
GRANT NO.: N/A
KEYWORDS: alcohol, pregnancy, public education, clinical
STUDY POP.: African-American women
The objective of this project is to develop and implement a public education campaign on the consequences of alcohol use during pregnancy for women in the Washington D.C. area. The campaign will be targeted toward African-American women and will contain messages and information geared specifically toward their needs in making informed decisions about drinking during pregnancy. The campaign will employ a variety of outreach methods. Amount funded: $125,000.
TITLE: Effect of Doxycycline on Osteoarthritis Progression
INSTITUTE: NIAMS
P.I: Dr. Kenneth Brandt
INSTITUTION: Indiana University
GRANT NO.: 1 R01 AR 43348 01
KEYWORDS: osteoarthritis, clinical trial, intervention, aging, clinical
STUDY POP.: Women
A randomized-placebo-controlled clinical trial examines the effect of this drug and its ability to prevent the progression of early knee osteoarthritis in women. The trial lasts 30 months and is co-funded by ORWH, FJIAMS, NIA, and the private sector. Amount funded: $200,000.
TITLE: Tolerance Induction by Monoclonal Antibodies
INSTITUTE: NIAID
P.I.: Dr. Peter Lipsky
INSTITUTION: University. of Texas SW Med. Center
GRANT NO.: 5 R01 AI 39230 02
KEYWORDS: immunotherapy, rheumatoid arthritis, T cells, autoimmune disease, treatment, clinical trials, clinical
STUDY POP.: Women and men
Rheumatoid arthritis is an inflammatory disease characterized by the intense infiltration of the synovium with mononuclear cells including CD4+ T cells. Study of these cells and their secreted products have suggested new forms of treatment using specific monoclonalantibodies or other biologic agents. In this project, experiments will determine whether treatment with a non-depleting anti-CD4 mAb, as well as with anti-lCAM- I, has a clinical benefit. Amount funded: $40,000.
TITLE: The Development of Conduct Disorder in Girls
INSTITUTE: NIMH
P.I.: Dr. Rolf Loeber
INSTITUTION: University of Pittsburgh
GRANT NO.: 1 RO1 MH56630 01A1
KEYWORDS: mental health, conduct disorder, behavior, cognition, emotion, clinical
STUDY POP.: Inner city prepubertal girls, African-American, Caucasian
The goal of this study is to examine the development of Conduct Disorder in a large (N=2,484) community sample of inner city prepubertal girls (ages 6 to 8), who are mostly African-American and Caucasian. There are three main aims. First, models that include behavioral, cognitive, and emotional factors will be tested. Second, factors that influence the development, continuity and severity of Conduct Disorder will be elucidated. Third, conditions that affect the course of Conduct Disorder will be identified. The proposed research will provide information on the etiology, comorbidity and prognosis of Conduct Disorder in girls. Amount funded: $350,000.
TITLE: Effects on Children of Treating Maternal Depression
INSTITUTE: NIMH
P.I.: Dr. Anne Riley
INSTITUTION: Johns Hopkins University
GRANT NO.: 1 RO1 MH58384 01
KEYWORDS: mental health, maternal depression, depression, children, environment, clinical
STUDY POP.: Women and their children, African-American, Caucasian, Hispanic
Maternal depression has devastating effects on the mental and physical health of children. This project will study the influence of treating maternal depression on children ages 5-11. This project will study 150 elementary-school aged children whose mother are depressed (50 Latina, 50 African American and 50 White) and 50 comparable children whose mothers are not depressed. Their mental health and functioning will be assessed by natural raters in their environments over a two-year time period that will link child functioning, symptomatology, and psychiatric disorders to mothers' symptomatology, parenting behavior, and family environment. Amount funded:$41,721.
TITLE: Genes, Environment, and Maternal Adjustments
INSTITUTE: NIMH
P.I.: Dr. David Reiss
INSTITUTION: George Washington University Medical Center
GRANT NO.: R01 MH54610
KEYWORDS: genes, maternal adjustment, mental health, family relationships, twins, personality, clinical
STUDY POP.: Women, men and children, Swedish Twin Registry
This study of 300 twin pairs, identified through the Swedish Twin Registry, their mothers, spouses and adolescent children, tests models of the interaction of direct and indirect and genetic and environmental influences on well-being. Genetic and social data are available for this cohort. Outcomes include personality, family relationships, characteristics of the husband. In cooperation with an international team, the study examines how a combination of family relationships and genetic factors affect positive and negative measures of mental health. Amount funded: $40,000.
TITLE: Study Commitment Inventory
INSTITUTE: NIDDK
P.I.: N/A
INSTITUTION: N/A
GRANT NO.: N/A
KEYWORDS: evaluation in human teens, compliance, assessment
STUDY POP.: Women and Girls
This is a new instrument to evaluate adherence to research protocols. The ancillary study evaluates this instrument and provides information on factors that affect compliance of girls and women with research protocols. Amount funded: $30,000.
TITLE: A Prospective Study of the Mental Health of Black Women
INSTITUTE: NIMH
P.I.: Dr. Margaret Ensminger
INSTITUTION: Johns Hopkins School of Hygiene and Public Health
GRANT NO.: 1 R01 MH 52336 01
KEYWORDS: mental health, African American, behavior, longitudinal, quality of life, retrospective, clinical
STUDY POP.: Women, African American
This project re-interviews a cohort of older African American women who were originally interviewed in 1966-67. At that time, each had a child in the first grade. Now the women range in age from 49-79. The study uses a framework both to model the continuity and change in these women's roles and their psychological and physical health since 1967. Amount funded: $35,000.
TITLE: Hair Dye Use and Risk of Non-Hodgkins Lymphoma
INSTITUTE: NCI
P.I.: Dr. Tongzang Zheng
INSTITUTION: Yale University
GRANT NO.: 3 R01 CA 62006 04
KEYWORDS: cancer, non-Hodgkins lymphoma, hair dye, chemical carcinogenesis, minorities, epidemiology, survey, clinical
STUDY POP.: Women, minorities
Studies from the American Cancer Society and others found a strong association between dark hair dye use and risk of non-Hodgkins Lymphoma (NHL). More rigorous epidemiologic studies are needed in different ethnic populations. This case-control study surveys women with confirmed NHL matched by age and ethnicity. Amount funded: $50,000.
TITLE: The Experience of Lung Cancer Survivorship
INSTITUTE: NCI
P.I.: Dr. Linda Sarna
INSTITUTION: University of California at Los Angeles
GRANT NO.: 1 RO1 CA78997 01
KEYWORDS: cancer, non-small cell lung cancer, quality of life assessment, smoking, tobacco, gender, clinical
STUDY POP.: Women and men who are lung cancer survivors
Little is known about gender differences after lung cancer. The purposes of this pilot study are to develop the most effective methods for recruitment of disease-free, lung cancer survivors, and to begin assessment of quality of life (QOL) outcomes of lung cancer. The physical, psychological, social, and existential dimensions of QOL will be assessed in 50 adults who are at least five years since diagnosis of non-small cell lung cancer. The variables of interest include gender, tobacco use, and pulmonary function. Amount funded: $100,000.
TITLE: Postmenopausal Hormonal Replacement Therapy after CABG
INSTITUTE: NHLBI
P.I.: Dr. Pamela Ouyang
INSTITUTION: Johns Hopkins University
GRANT NO.: 1 U01 HL5084 01A2
KEYWORDS: heart disease, hormone replacement therapy, bypass surgery, aging, atherosclerosis, vein grafts, clinical
STUDY POP.: Postmenopausal women
This randomized, clinical trial tests the hypothesis that postmenopausal hormone replacement therapy will benefit women who have undergone coronary bypass surgery. The subjects, 160 postmenopausal women who have had coronary artery bypass graft (CABG), will be randomized to HRT or placebo within 2 weeks of surgery. Outcomes are occurrence of later graft occlusion and delay of atherosclerosis in the graft. Pathophysiological mechanisms causing acute closure and atherosclerosis of vein grafts will be explored. Amount funded: $130,000.
TITLE: Eating Disorders in Young Women: Prevalence and Risk
INSTITUTE: NCI
P.I.: Dr. Ruth Striegel-Moore
INSTITUTION: Wesleyan University
GRANT NO.: 1 RO1 MH57897 01
KEYWORDS: eating disorders, binge eating disorders, retrospective, assessment, clinical
STUDY POP.: Minority and non-minority women
Current knowledge of binge eating disorders is limited by (a) the virtual exclusion of minority women (b) the paucity of studies of women with a spectrum binge eating disorders; and © retrospective assessment of exposure to risk. The proposed study will assess a cohort of over 2,000 young adult black and white women to determine prevalence and describe the spectrum of binge eating disorders. Amount funded: $100,000
TITLE: Treatment of Bulimia Nervosa in a Primary Care Setting
INSTITUTE: NIDDK
P.I.: Dr. Bernard Walsh
INSTITUTION: New York State Psychiatric Institute
GRANT NO.: 1 RO1 DK56131 01A1
KEYWORDS: eating disorder, bulimia nervosa, fluoxetine, guided self-help, primary care setting, antidepressant, clinical
STUDY POP.: Women
The aim of this proposal is to examine whether the two treatments of an antidepressant medication (fluoxetine) or a form of cognitive behavioral therapy (guided self help) can be usefully transferred to general health care settings. Over four years, 200 women with bulimia nervosa will be treated in a suburban primary care setting and randomized to receive 1) fluoxetine or placebo and 2) guided self-help combined with medical management or medical management alone. Changes in eating behavior and in psychological state will be assessed at the end of active treatment (4 months) and 4 and 8 months after the end of treatment. Amount funded: $100,000.
TITLE: Serum Lipid Measurements as an Outcome Measure
INSTITUTE: NIDDK
P.I.: Steering Committee for DPP
INSTITUTION: N/A
GRANT NO.: N/A
KEYWORDS: diabetes, noninsulin-dependent diabetes mellitus, diabetes prevention, serum lipids, cardiovascular risk, behavior, clinical
STUDY POP.: Women and men
The Diabetes Prevention Program (DPP) is an NIH-sponsored multi-center study with the specific objective of comparing, in high risk individuals, the efficacy of three intervention methods (intensive behavior modification, metformin, and troglitazone) vs control placebo group in preventing or delaying conversion of impaired glucose tolerance (IGT) to non-insulin dependent diabetes mellitus (NIDDM). The Diabetes Prevention Program (DPP) is a major, randomized, multicenter, controlled clinical trial for prevention of noninsulin dependent diabetes mellitus through behavioral change. Serum lipids are expected to be abnormal in 50-60% of DPP enrollees. Repeated lipid determinations are used to assess cardiovascular risk and the effect of DPP interventions on that risk. Award funded: $200,000.
TITLE: Mechanisms of Action of DPP Interventions in Women
INSTITUTE: NIDDK
P.I.: Dr. Abbas Kitabchi
INSTITUTION: University of Tennessee
GRANT NO.: 1 RO1 DK53061 01
KEYWORDS: diabetes, noninsulin dependent diabetes mellitus, impaired glucose tolerance, risk, ethnic variation, interactions, clinical
STUDY POP.: Women, Caucasian, African-American, Hispanic
The Diabetes Prevention Program (DPP) is an NIH-sponsored multi-center study with the specific objective of comparing, in high risk individuals, the efficacy of three intervention methods (intensive behavior modification, metformin, and troglitazone) vs control placebo group in preventing or delaying conversion of impaired glucose tolerance (IGT) to non-insulin dependent diabetes mellitus (NIDDM). This study should provide information on mechanisms of NIDDM and the basis for ethnic variation between Caucasian, African American and Hispanic women in disease risk and outcome. Amount funded: $265,000.
TITLE: Antibodies to Recombinant Autoantigens – Prediction/Immunogenetics
INSTITUTE: NIAID
P.I.: Dr. George Eisenbarth
INSTITUTION: Davis Center for Childhood Diabetes
GRANT NO.: 2 R01 A139213 02
KEYWORDS: immunotherapy, diabetes, IDDM. autoantigen, genetics, insulin, immunology, clinical
STUDY POP.: Participants in the Diabetes Prevention Trial ( DPT- I )
The on-going Diabetes Prevention Trial tests the hypothesis that daily prophylactic injections of insulin therapy, prior to disease onset, can prevent insulin dependent diabetes mellitus (IDDM) in first degree relatives of patients with cytoplasmic islet cell antibody (ICA). This study, involving screening of first degree relatives with IDDM, assigns patients to experimental or control groups based on the level of islet cell autoantibodies. The research tests the ability of such screening to help predict IDDM and to understand the natural history of pre-type I diabetes. Specific experiments examine other related hypotheses about autoantibodies and progression to disease. Amount funded: $40,000.
TITLE: Mechanisms of Immunotherapy in IDD Prevention Trials
INSTITUTE: NIAID
P.I.: Dr. Mark Atkinson
INSTITUTION: University of Florida
GRANT NO.: 5 R01 A139250 02
KEYWORDS: immunotherapy, diabetes, IDDM. autoantigens, insulin, clinical
STUDY POP.: Women and men, Diabetes Prevention Trial
Prior animal and human research has shown that daily prophylactic injections of insulin prior to onset of clinical symptoms may prevent the onset of insulin dependent diabetes mellitus (IDDM). This study is planned to delineate the mechanism of disease prevention by evaluating the effects of tolerization/suppression of the immune responses to islet cell antigens. Findings could aid in understanding the beneficial effects for this form of immunotherapy. Amount funded: $40,000.
TITLE: Cellular Mechanisms of Endocrine Disruptors
INSTITUTE: NIEHS
P.I.: Dr. Stuart Adler
INSTITUTION: Washington University
GRANT NO.: 5 R01 ES07902 02
KEYWORDS: environment, endocrine disruptors, estrogen, insecticides, plasticizers, dioxin gene regulation, basic
STUDY POP.: N/A
Many compounds such as insecticides, plasticizers, and dioxin may be classified as environmental estrogens or endocrine disruptors. Exposure to these may affect women's health. This study examines a panel of chemicals to determine their potential to affect women and their offspring. For example, gene regulation studies in tissue culture systems are used to determine the capacity of these compounds to participate in estrogenic gene regulation. The potential of these compounds in estrogenic and non-estrogenic pathways related to gene regulation is investigated. Awarded under RFA ES-96-003.
TITLE: Fetal PCB Exposure, Thyroid Function and Neurodevelopment
INSTITUTE: NIEHS
P.I.: Dr. Ira Hertz-Picciotto
INSTITUTION: University of North Carolina
GRANT NO.: 5 R01 ES07563 02
KEYWORDS: PCB, environment, thyroid, fetal development, hypothyroidism, pregnancy, maternal, hormones, cognitive development, hearing loss, speech, birth defects, clinical
STUDY POP.: Women and men
Research suggests that at least one pathway by which dioxins and polychlorinated biphenyls (PCBs) exert toxicity is through interference with thyroid function. Hypothyroidism during pregnancy may be associated with serious birth defects. This retrospective cohort study will assess specific PCB congeners measured during pregnancy in an exposed population. Maternal thyroid hormones, cognitive development, hearing loss, and speech problems will be correlated with PCB exposure. Awarded under RFA ES-96-003.
TITLE: PAH Action on Ovarian Steroidogenesis
INSTITUTE: NIEHS
P.I.: Dr. Reinhold Hutz
INSTITUTION: University of Wisconsin
GRANT NO.: 5 R01 ES08342 02
KEYWORDS: endocrine disruptors, ovarian function, cell death, reproductive health, PAM, programmed cell death, steroids, basic
STUDY POP.: N/A
Polycyclic aromatic hydrocarbons (PAM) are endocrine-disrupting chemicals. They may affect female reproduction by impairing ovarian follicular health through cellular degeneration, programmed cellular death, or by altered steroid synthetic capability. This study examines whether these environmental chemicals exert untoward effects on ovarian follicle health related to impaired reproductive function in women. Awarded under RFA ES-96-003.
TITLE: Environmental Estrogen Receptors in ER Minus Mice
INSTITUTE: NIEHS
P.I.: Dr. Dennis Lubahn
INSTITUTION: University of Missouri
GRANT NO.: 5 R01 ES08272 02
KEYWORDS: environment, endocrine disruptors, estrogen, receptors, molecular, NCER, methoxychlor, basic
STUDY POP.: Animal model (Gene-knockout mouse)
The investigators are using the estrogen receptor knock mouse to investigate estrogenic and estrogen response, protein functions, and to identify molecular mechanisms that mediate receptor functions. It is hypothesized that methoxychlor and other biologically important estrogens work, in part, through their own nonclassical estrogen response (NCER) proteins. NCER receptors can be characterized in an animal model. Awarded under RFA ES-96-003.
TITLE: Developmental Effects of Xenoestrogens
INSTITUTE: NIEHS
P.I.: Dr. Ana Soto
INSTITUTION: Tufts University
GRANT NO.: 5 R01 ES08314
KEYWORDS: environment, endocrine disruptors, estrogens, reproductive health, oviduct, uterus, bisphenol A, fertility, basic
STUDY POP.: N/A
This research examines the hypothesis that specific environmental agents will produce irreversible alterations in the development and physiological function of estrogen responsive tissues in the female oviduct and uterus. Such changes result in sub-optimal fertility. The study focuses on the commonly used xenoestrogen, bisphenol A, as it affects female genital tract development and fertility. Awarded under RFA ES-96-003.
TITLE: Phytoestrogens, Organochlorines, and Fibroid Risk
INSTITUTE: NIEHS
P.I.: Dr. Stephen Schwartz
INSTITUTION: Fred Hutchinson Cancer Research Center
GRANT NO.: 5 R01 ES08305 02
KEYWORDS: environment, endocrine disruptors, uterine fibroids, diet, soy grains, hormones, biomarkers, phytoestrogen, organochlorine, clinical
STUDY POP.: Women
Phytoestrogens and organochlorine compounds are two classes of putative endocrine disruptors present in dietary sources, primarily soy foods and grains. The growth of uterine fibroids is highly dependent on ovarian hormones and may be related to these environmental sources. A population-based, case control study is being conducted to determine whether biomarkers of exposure to these compounds is related to a woman's risk of uterine fibroids. Awarded under RFA ES-96-003.
TITLE: Effects of Endocrine Disruptors on Offspring
INSTITUTE: NIEHS
P.I.: Dr. Frederick von Saal
INSTITUTION: University of Missouri
GRANT NO.:5 R01 ES08293 02
KEYWORDS: environment, endocrine disruptors, reproductive health, diet, bisphenol A, maternal, reproductive development, lactation, basic
STUDY POP.: Animal (mice)
Bisphenol A is used in the manufacture of resin coating of food and beverage cans and in polycarbonate food and drink containers and may migrate into the food during the sterilization process. Using male and female (mice) offspring, the investigators examine the consequences on reproductive organ development associated with maternal ingestion of bisphenol A during pregnancy and lactation. Awarded under RFA ES-96-003.
TITLE: Environmental Estrogens and Uterine Leiomyoma
INSTITUTE: NIEHS
P.I.: Dr. Cheryl Walker
INSTITUTION: U.T. M.D. Anderson Cancer Center
GRANT NO.: 5 R01 ES08263 02
KEYWORDS: environment, endocrine disruptors, fibroids, estrogen, neoplasm, hormones, basic
STUDY POP.: Animal (Erker rat)
Uterine leiomyomas (fibroids) are the most frequent gynecologic neoplasm in women. In this research, investigators use female Erker rats (susceptible to fibroids due to a germline tumor suppressor gene mutation) to examine responsiveness of leiomyomas to environmental estrogens. Experiments with these rats in an in vitro/in vivo model system will investigate the hormonal responsiveness of leiomyomas. It is hoped to yield new insights leading to in vitro assays predictive of the activity of exogenous estrogens in vivo. Awarded under RFA ES-96003.
TITLE: Lead, Endocrine Disruption, and Reproductive Outcomes
INSTITUTE: NIEHS
P.I.: Dr. Xiping Xu
INSTITUTION: Harvard University
GRANT NO.: 5 R01 ES08337 02
KEYWORDS: environment, endocrine disruptors, reproductive health, lead, Chinese, prospective, hormones, urinary, menses, pregnancy, fertility, clinical
STUDY POP.: Chinese women
This prospective study of a Chinese cohort assesses the effects of lead exposure on endocrine dysfunction and later adverse outcomes. Dysfunction is monitored by urinary hormone metabolites and the study endpoints will include menstrual disturbance, time to conception, preterm delivery, and low birth weight. Awarded under RFA ES-96-003.
TITLE: Organochlorine Compounds and Menstrual Cycle Function
INSTITUTE: NIEHS
P.I.: Dr. Gayle Windham
INSTITUTION: Californian Public Health Foundation
GRANT NO.: 5 R01 ES0832 02
KEYWORDS: environment, endocrine disruptors, diet, reproductive health, Laotian, pesticide, ovary, menses, clinical
STUDY POP.: Laotian women
This research examines whether women who have been exposed to chlorinated pesticides have alterations in their ovarian function as measured by frequency of menstrual cycle disturbance. Laotian immigrants are frequent consumers of fish from the San Francisco Bay which have contamination levels above health protective advisories. The study proposes a link between this dietary pattern and ovarian function. Awarded under RFA ES-96-003.
TITLE: Mechanisms of Action of Environmental Anti-androgens
INSTITUTE: NIEHS
P.I.: Dr. Elizabeth Wilson
INSTITUTION: University of North Carolina
GRANT NO.: 5 R01 ES08265 03
KEYWORDS: environment, endocrine disruptors, reproductive health, industrial chemicals, fungicides, fetal development, sperm counts, hypospadia, androgens, fertility, survey, basic
STUDY POP.: Tissue/cell culture
Evidence suggests that environmental anti-androgens exist among industrial chemicals, pesticides and fungicides that may invoke detrimental effects on the development of the male fetus. Prior surveys indicate sperm counts have decreased in some parts of the world with high levels of such industrial chemicals and the incidence in reproductive tract abnormalities such as hypospadias deformity has increased. This research examines the mechanistic basis for anti-androgenic activity and its effects on reproductive development in the male. Awarded under RFA ES-96003.
TITLE: PCB and Thyroid Hormone Action in Developing Cochlea
INSTITUTE: NIEHS
P.I.: Dr. Robert Zoeller
INSTITUTION: University of Massachusetts at Amherst
GRANT NO.: 5 RO1 ES08333 02
KEYWORDS: environment, endocrine disruptors, PCB, thyroid, cochlea, organochlorine, development, dioxin, biphenol, gene expression, basic
STUDY POP.: Animal (rat)
This project tests the hypothesis that developmental exposure to organochlorines can disrupt development by interfering with the thyroid hormone function in the fetal brain. Polychlorinated biphenols and dioxin are particularly implicated as having deleterious effects on the developing cochlea. Investigations are to examine PCB and expression of thyroid hormone receptors, the retinoid acid receptors during development of the inner ear. Exposure to a specific PCB mixture is hypothesized to produce morphological abnormalities similar to hypothyroidism and that such exposure disrupts the known sequence of gene expression in the developing cochlea. Awarded under RFA ES-96-003.
TITLE: PC8s, Thyroid Hormones, and CNS development
INSTITUTE: NIEHS
P.I.: Dr. Joseph Jacobson
INSTITUTION: Wayne State University
GRANT NO.: 5 R01 ES07902 OlAI
KEYWORDS: environment, endocrine disruptors, PCBs, thyroid, birth defects, behavior, cognition, diet, clinical
STUDY POP.: Women and children, Native American, Inuit
Longitudinal studies have linked in-utero exposure to polychlorinated biphenyls (PCBs) to cognitive and behavioral deficits in offspring. The Alaska Native Inuit population is highly exposed to PCBs due to atmospheric and oceanic transport of these compounds and to the bioaccumulation in fish and sea mammals, staples of the Inuit diet. Dr. Jacobson and colleagues are conducting a study of pregnant Inuit women and their newborn infants. This native population in Northern Canada has a very high level of exposure to PCBs and other organochlorines because they eat whale blubber and other sea mammal and fish products from the arctic seas. These chemicals bioaccumulate in adipose tissue and these sea mammals and fish have high levels of contamination. Body burden will be measured. The children are being followed up for development endpoints in the motor and cognition domains. There is a special emphasis on measuring thyroid hormones as well as it thought that these chemicals may exert their endocrine disrupting effects on growth and development through the neuroendocrine axis and thyroid function may be effected. Awarded under RFA-ES96-003.
TITLE: Prenatal Exposure to Organochlorine and Fecundability
INSTITUTE: NIEHS
P.I.: Dr. Barbara Cohn
INSTITUTION: Public Health Institute
GRANT NO.: 1 RO1ES08345 01A2
KEYWORDS: organochlorine pesticides, fecundability adverse reproductive health, DDT, DDE, development, pregnancy, fertility, estrogen, clinical
STUDY POP.: Mother-daughter pairs
This project will study the developmental effects of exposure to organochlorine pesticides, such as DDT/DDE and PCBs on adult female reproductive function. The study population consists of 312 mother/daughter pairs assembled between 1960 and 1963 and followed for more than 30 years since the mother's pregnancy. Blood specimens were collected during pregnancy and stored. The adult daughters were asked to provide information on their reproductive history and time to pregnancy during an interview. Estrogen levels were analyzed in blood. Maternal blood will be analyzed for organochlorine compounds which have been purported to disrupt endocrine activity and may result in adverse reproductive effects. Amount funded: $86,137.
TITLE: Genetics of Age-Related Macular Degeneration
INSTITUTE: NEI
P.I.: Dr. Michael Klein
INSTITUTION: Oregon Health Sciences University
GRANT NO.: 1 RO1 EY12203 01
KEYWORDS: blind, age-related macular degeneration, gender differences, genetics, linkage, clinical
STUDY POP.: Women and men, AMD Families.
The incidence of Age-related Macular Degeneration (AMD) continues to rise in the population as the result of the increasing percentage of elderly persons with women at 50% greater risk than men. This application seeks to characterize genes that cause AMD. Dr. Klein has access to a number of AMD families and he will map the genetic loci co-segregating with the disease in these families. To achieve this goal he plans to 1) continue to collect and ascertain families with the disease, 2) perform genome-wide screening of AMD families, 3) fine-map loci suggestive of linkage, and 4) identify specific genetic mutations in these families. Amount funded: $100,000.
TITLE: Molecular Genetics of Macular Degeneration
INSTITUTE: NEI
P.I.: Dr. Edwin Stone
INSTITUTION: University of Iowa
GRANT NO.: 1 RO1 EY09406 05
KEYWORDS: blind, macular degeneration, molecular genetics, Best's disease, clinical
STUDY POP.: Women and men, families with dominant macular dystrophy with flecks
Macular degeneration is the leading cause of legal blindness in patients over the age of 55 in developed countries. The specific aims of this project are to: 1) isolate and characterize the gene that causes Best's disease and refine the chromosomal location of a condition known as Dominant Macular Dystrophy with Flecks; 2) map the disease-causing genes in additional families with early and late-onset (age related) macular diseases; 3) investigate the potential allelic relationship between late-onset macular degeneration and earlier-onset dystrophies; 4) test a panel of high priority candidate genes for evidence of involvement in macular disease; and 5) explore the possibility that triplet repeats play a role in macular degeneration. Amount funded: $100,000.
TITLE: Neural Control of Lacrimal Gland Secretion
INSTITUTE: NEI
P.I.: Dr. Benjamin Alcott
INSTITUTION: State University of New York at Stony Brook
GRANT NO.: 2 RO1 EY09406 05
KEYWORDS: dry eye, lacrimal gland, Sjogren's, basic
STUDY POP.: Animals (Normal, MRL and NZB strains mice)
Dry eye is a debilitating disease particularly in older women and can be associated with inflammatory changes in the lacrimal gland when associated with Sjogren's syndrome. The MRL and NZB strains of mice as well as normal mice will be used to determine what processes in the stimulus-secretion pathway have been affected by the disease. Immunocytochemistry will be used to detail the normal pattern of innervation of the lacrimal glands and to determine the neurotransmitter present. Examination of diseased glands will help elucidate the effects of infiltration on innervation. Amount funded: $168,875.
TITLE: Stromal-Epithelial Interactions in the Bladder
INSTITUTE: NIDDK
P.I.: Dr. Gerald Cunha
INSTITUTION: University of California at San Francisco
GRANT NO.: 5 R01 DK51397 02
KEYWORDS: bladder, cell stroma, smooth muscle, urinary, growth factors, basic
STUDY POP.: Animal model
This project investigates the role of growth factors as mediators of stromal-epithelial interactions in bladder development and dysfunction. Using an experimental model of urethral obstruction in which bladder signaling mechanisms will be studied under hypertrophy. A hypothesis is tested that cell-cell interactions are mediated by the local production and action of growth factors and other paracrine acting mediators. Awarded fund under RFA DK-95-007.
TITLE: Extracellular Modulation of Urothelial Permeability
INSTITUTE: NIDDK
P.I.: Dr. Simon Lewis
INSTITUTION: University of Texas Medical Branch at Galveston
GRANT NO.: 5 R01 DK51382 02
KEYWORDS: interstitial cystitis, bladder, protein structure, basic
STUDY POP.: N/A
This study is concerned with mechanisms by which the urinary bladder epithelium maintains near constant urinary composition (bladder barrier function). Previous studies have shown that cationic proteins can compromise the barrier function of the bladder. Investigators use electrophysiological methods and confocal microscopy to determine the mechanisms by which these proteins cause cell Iysis, investigate other possible sites of protein action, and then develop a method to counter the effects of these proteins on the bladder epithelial cells. Award funded under RFA DK-95-007.
TITLE: Sodium Channels in the Mammalian Urinary Bladder
INSTITUTE: NIDDK
P.I.: Dr. Thomas Kleyman
INSTITUTION: University of Pennsylvania Medical Center
GRANT NO.: 5 R01 DK51391 02
KEYWORDS: bladder, sodium, epithelial, urinary, solute transport, basic
STUDY POP.: Animal models, (mouse/rabbit)
Using both mouse and rabbit models, this set of experimental procedures seeks new information regarding the physiology of solute transport in the urinary bladder and to provide a framework for characterization of altered solute transport in selected disorders of the urinary bladder. Sodium is a major solute reabsorbed across epithelial cells into the kidneys and bladder. Experiments examine the epithelial sodium channel. Award funded under RFA DK-95-007.
TITLE: Biochemistry of Urothelial Differentiation
INSTITUTE: NIDDK
P.I.: Dr. Tung-Tien Sun
INSTITUTION: New York University Medical Center
GRANT NO.: R01 DK 39753
KEYWORDS: urinary tract, membrane, epithelial, bladder barrier, basic
STUDY POP.: Animal tissue
Bladder epithelium functions to expand during bladder distention and as a permeability barrier. This study focuses on the surface plaques, that may contribute to the urothelial permeability barrier and perform other functions. Investigators also include study of the regulation of asymmetric unit membrane assembly and AUM/cytoskeletal interaction. Award funded under RFA DK-95-007.
TITLE: Spinal Pathways Mediating Bladder Pain and Hyperactivity
INSTITUTE: NIDDK
P.I.: Dr. William De Groat
INSTITUTION: University of Pittsburgh
GRANT NO.: 5 R01 DK51402 02
KEYWORDS: urinary, bladder, pain, spinal cord injury, nervous system, voiding, basic
STUDY POP.: Animal model, chronic spinal cord injury
Pathways in the brain and spinal cord function to bring about urine storage or release. In adults, voiding is controlled by voluntary brain mechanisms. Capsaicin-sensitive, C-fiber bladder afferents are shown to activate spinal mechanisms to mediate bladder function. Investigators use a chronic spinal cord injury model of voiding function to test hypotheses related to the role of spinal interneuronal pathways and how disruption results in dysfunction. Award funded under RFA DK-95-007.
TITLE: Bladder Hyperactivity After Obstruction Relief
INSTITUTE: NIDDK
P.I.: Dr. William Steers
INSTITUTION: University of Virginia
GRANT NO.: 5 R01 DK51364 02
KEYWORDS: bladder, urinary incontinence, capsaicin, smooth muscle, voiding, basic
STUDY POP.: Animal model (rat)
Obstruction of the urinary bladder from prostatism or, less commonly an obstruction in the female bladder, can result in urinary incontinence. Investigators, using a rat model, examine the ability of rats to reverse obstruction-induced smooth muscle and neural changes. Results may provide insight into the mechanisms for hyperactive voiding. Use of agents to inhibit nerve growth factor or block its action offer a potential basis for future clinical trials. Award funded under RFA DK-95-007.
TITLE: Heparin Binding Factors in Bladder Inflammation/ Revision
INSTITUTE: NIDDK
P.I.: Dr. Anthony Tala
INSTITUTION: Children's Hospital in Boston
GRANT NO.: 5 R01 DK49484 02
KEYWORDS: bladder, epidermal growth factor, inflammation. smooth muscle, heparin, basic
STUDY POP.: Animal model
The epidermal growth factors amphiregulin and heparin-binding growth factors (HBEGF) are physiologic regulators of inflammatory processes in the bladder. This study has a number of specific aims related to HB-EGF in the bladder that include work with smooth muscle cells, cellular differentiation, and sites for expression of EGF in the bladder under varying conditions. Award funded under RFA DK-95-007.
TITLE: Neurogenic Inflammation in Interstitial Cystitis
INSTITUTE: NIDDK
P.I.: Dr. Leslie Kushner
INSTITUTION: Long Island Jewish Medical Center
GRANT NO.: 5 R29 DK49450 02
KEYWORDS: interstitial cystitis, bladder, neurogenic inflammation, pain, pelvic, immunology, clinical
STUDY POP.: Human and animal model (rat)
The cause of interstitial cystitis is unknown, but the observation of chronic pelvic pain without evidence of infection suggests that neurogenic inflammation may be related to a cause of the disease. This project demonstrates the induction of neurogenic inflammation in chemically induced cystitis in the rat. The bladder is expected to mount a neuronally provoked local immune response. The model can then be used for testing prevention and treatment strategies targeted at blocking neurogenic inflammation. Award funded under RFA DK-95-007.
TITLE: Irritation Induced Plasticity of Micturition Pathways
INSTITUTE: NIDDK
P.I.: Dr. Margaret Vizzard
INSTITUTION: University of Vermont and State Agriculture College
GRANT NO.: 5 R29 DK51369 02
KEYWORDS: interstitial cystitis, bladder. spinal cord, smooth muscle, nervous system, nitric oxide, basic
STUDY POP.: Animal
The working hypothesis for this research is that one component of interstitial cystitis involves an alteration of visceral sensation/bladder sensory physiology. Specific studies focus on the sacral parasympathetic nucleus, spinal neurons, and nitric oxide-induced changes in bladder afferent information from the spinal cord following chronic bladder irritation. Elucidation of the neural control mechanisms and pathways in the lower urinary tract is needed to shed light on a number of clinical bladder disorders resulting from diseases or injuries. Award funded under RFA DK95-007.
TITLE: Pregnancy and Hormone Effects on Kidney and Urinary Tract
INSTITUTE: NIDDK
P.I.: Dr. Linda Shortliffe
INSTITUTION: Stanford University
GRANT NO.: 5 R01 DK51419 02
KEYWORDS: urinary, estrogen, hormones, pregnancy, kidney, urinary incontinence, smooth muscle, renal, blood flow, steroids, parturition basic
STUDY POP.: Animal models (rat and rabbit)
Using rat and rabbit models, this project will examine renal and urinary tract changes in estrogen and progesterone levels associated with pregnancy and the postpartum period. Variables investigated include smooth muscle changes in pregnancy, global and renal blood flow, bladder and other tissue changes under different adrenergic and cholinergic drugs, and changes in collagen architecture and distribution after parturition. Award funded under RFA DK-95-007.
TITLE: Oral Contraceptives and Hormonal Replacement in SLE
INSTITUTE: NIAMS
P.I. Dr. Jill Buyon
INSTITUTION: Hospital for Joint Diseases
GRANT NO.: U01 AR42540
KEYWORDS: SLE, Lupus, autoimmune, hormone replacement, reproductive health, clinical trial, HRT, oral contraceptives, clinical
STUDY POP.: Women, African-American predominately
Oral contraceptives and hormone replacement are not generally prescribed for women with systemic lupus erythematosus (SLE or Lupus). The disease is most common among women of color. This clinical trial, a cooperative agreement, tests the effect of low dose hormones on disease activity in women with SLE. Amount funded: $450,000.
TITLE: Specialized Center of Research in Scleroderma
INSTITUTE: NIAMS
P.I.: Dr. Frank C. Arnett
INSTITUTION: Univ of Texas Medical School, Houston
GRANT NO.: 1 P50 AR4488 01
KEYWORDS: scleroderma, molecular, behavior, collagen, genetics, demography, lupus, ethnicity, clinical
STUDY GROUP: Native American, Oklahoma, Choctaw, Animal model (mice)
The interrelated projects in this specialized center offer a range of basic and clinical studies on scleroderma. Genetic studies will be used to map a unique human model for the disease in the Oklahoma Choctaw. Molecular research using a mouse model is to address fundamental questions about collagen dysregulation. Finally, sociodemographic and behavioral factors on outcome in systemic sclerosis, modeled on a lupus study, will examine the effect of ethnicity on outcome. Amount funded: $300,000.
TITLE: Immunotherapy of Psoriasis – Mechanism of DAB 389 IL2
INSTITUTE: NIAID
P.I.: Dr. James Krueger
INSTITUTION: Rockefeller University
GRANT NO.: 1 RO1 AI39214
KEYWORDS: immunotherapy, autoimmune disease, psoriasis, pharmacokinetics, clinical
STUDY POP.: Human tissue culture
Psoriasis, the most common human autoimmune disorder, is advantageous as a model for research on immunotherapy. This project investigates treatment with DAB389IL-2, a novel fusion toxin which reacts only with cells expressing high affinity to IL-2R which characterizes this disorder. Amount funded: $40,000.
TITLE: Costimulatory Mechanisms of Autoimmunity
INSTITUTE: NIAID
P.I.: Dr. David Hafler
INSTITUTION: Brigham and Women's Hospital
GRANT NO.: 1 PO1 AI39671 01A1
KEYWORDS: autoimmune disease, multiple sclerosis, T cell, immunology, immunotherapy, basic
STUDY POP.: Animal model
The goal of this project is to determine whether B7-1 and B7-2 costimulatory molecules may provide a signal which can induce either the afferent or efferent phases of autoreactive T cell activation leading to pathologic immune disease. Signaling via the B7-CD28/ CTLA4 pathway can provide a potent costimulatory signal for T cell activation. For this reason, methods directed toward blocking this pathway have received attention for the treatment of autoimmune disease. B7-CD28/CTLA4 pathway blockade may enable a distinctive treatment strategy, since it would affect only those antigen-specific T cells undergoing activation and not be globally immunosuppressive. Amount funded: $20,000.
TITLE: Immunologic Mechanism in Lupus Nephritis
INSTITUTE: NIDDK
P.I.: Dr. Michael Madaio
INSTITUTION: University of Pennsylvania
GRANT NO.: 2 RO1 DK33694 15A1
KEYWORDS: autoimmune, SLEs, autoantibodies, glomerular
STUDY POP.: Women and men and animals models (mice)
The aim of this project is to develop a better understanding of the immunologic events leading to the glomerular immune deposit formation in individuals with Systemic Lupus Erythematosus (SLE). A goal of this project is to identify the glomerular cell surface antigens for three nephritogenic lupus autoantibodies. The results should identify disease-relevant glomerular antigens for pathogenic lupus autoantibodies and provide insights into the overall pathogenic relevance of autoantibody-glomerular cell surface antigen interactions in lupus nephritis. Amount funded: $75,000.
TITLE: Prevention of Maternal and Congenital CMV Infection
INSTITUTE: NIAID
P.I.: Dr. Robert Pass
INSTITUTION: University of Alabama at Birmingham
GRANT NO.: 1 PO1 AI43681 01
KEYWORDS: sexually transmitted disease, intrauterine infection, CM, uterine, deafness, mental retardation, pregnancy, vaccines, antivirus, STD's, clinical
STUDY POP.: Pregnant women and their infants
Congenital cytomegalovirus (CMV) is the most common intrauterine infection in the US, occurring in 0.4-2.3 percent of all live births. About 3,000-4,000 infected newborn infants per year have symptomatic CMV disease; of those who survive, most suffer from profound progressive deafness and/or mental retardation. Congenital CMV may be the cause of 20-40 percent of congenital deafness and is as frequent a cause of mental retardation as the fragile X chromosome. An additional 4,500-6,000 children who are asymptomatic at birth also develop serious handicaps. The highest risk for congenital CMV infection is among infants born to mothers who have had primary infection during pregnancy. This proposal will study vaccines and antiviral evaluations to understand how to prevent congenital CMV infections and/or disease. Amount funded: $150,000.
TITLE: Mid-America Adolescent STD Cooperative Research Center
INSTITUTE: NIAID
P.I.: Dr. Donald Orr
INSTITUTION: Riley Hospital, Indianapolis, IN
GRANT NO.: 1 U19 AI43924 01
KEYWORDS: infectious diseases, sexually transmitted diseases, STD, longitudinal, behavior protective factors, genital track, clinical
STUDY POP.: Adolescents
The purpose of this project is to conduct integrated, multi disciplinary research on the important issues related to sexually transmitted infections in adolescents. The goal is to examine longitudinally the behavioral, psychosocial and biological risk and protective factors related to sexually transmitted infections of the lower genital tract among adolescent women. Amount funded: $60,000.
TITLE: Microbicidal Lactobacilli for Prevention of Genital Infection
INSTITUTE: NIAID
P.I.: Dr. Sharon Hillier
INSTITUTION: Magee Womens Hospital
GRANT NO.: 2 U19 AI 38513 03
KEYWORDS: infectious diseases, genital infection, lactobacilli, microbicidal, vagina, bacterial vaginosis, gonorrhea, HIV, clinical
STUDY POP.: Adolescent girls, Inner city
Lactobacilli, endogenous flora of the human vagina, secrete hydrogen peroxide which kills bacteria and inactivates viruses, including HIV. These bacteria prevent bacterial vaginosis, gonorrhea and HIV infection. There is the potential for these endogenous bacteria to be used as vectors to deliver protective molecules such as monoperoxidase, which can enhance the killing activity of the hydrogen peroxidase in the vagina. Other defensive molecules and neutralizing antibodies could also be secreted by genetically engineered lactobacilli. Amount funded: $90,000.
TITLE: PRO 2000, A Novel Topical Microbicide for the Prevention of HIV Transmission
INSTITUTE: NIAID
P.I.: Dr. George Seage
INSTITUTION: ABT Associates, Inc.
GRANT NO: NO1 AI35176 (DMC); NO1 AI35173(IMC); NO1 AI45200(SC)
KEYWORDS: infectious diseases, HIV, microbicide, prevention, herpes, chlamydia, clinical trials, vagina, PRO 2000/5, clinical
STUDY POP.: Women
PRO 2000/5 gel was chosen for study because of its activity in-vitro against HIV-1 strains from developed as well as developing countries and its activity against herpes viruses and Chlamydia trachomatis. Two, Phase I clinical trials conducted in Europe showed that repeated intra vaginal applications of two concentrations of PRO 2000/5 gel(0.5% and 4.0%) were safe and well tolerated. The goal of this multi-center Phase I study is to determine the safety and tolerance of 4.0% PRO 2000/5 gel for use as a vaginal microbicide and to make a preliminary assessment of the product's acceptability. Amount funded: $1,000,000.
TITLE: Regulation of Estrogen-Responsive Genes
INSTITUTE: NICHD
P.I.: Dr. Marilyn Evans
INSTITUTION: West Virginia University School of Medicine
GRANT NO.: 2 RO1 HD2633910
KEYWORDS: estrogen, estrogen-responsive genes, transcription, molecular, apolipoproteins, RNA, basic
STUDY POP.: Animal model (birds)
The long term objective of this research is to understand the molecular basis by which estrogen regulates the transcription of genes. The avian liver provides a model system in which estrogen-responsive genes direct the synthesis of egg yolk precursor proteins. The specific aims of this proposal are to 1) define the estrogen-dependent chromatin alterations and transcription response of the vitellogenin (VT-II) gene, 2) determine the characteristics of the secondary response of apolipoproteins (apo-II) and VT-II to estrogen, and 3) isolate and characterize mRNAs that are altered during the response to estrogen. The techniques that will be relied on are run-on transcription assays, in vivo foot printing and subtractive cloning techniques. Amount funded: $172,673.
TITLE: Peri-Menopausal Mobilization of Lead from Bone
INSTITUTE: NIEHS
P.I.: Dr. Susan Muldoon
INSTITUTION: University of Florida
GRANT NO.: 5 R29 ES07052 03
KEYWORDS: menopause, lead, bone density, life style, behavior, aging, blood chemistry, osteoporosis, prospective, longitudinal, clinical
STUDY POP.: Women, pre-, peri-, and postmenopausal
National data show significantly higher blood lead levels in postmenopausal women than in premenopausal women. The investigator hypothesizes that bone lead may be mobilized via osteoporosis bone loss in older women. A prospective, longitudinal study will collect data as a cohort of women moves through perimenopause. Amount funded FY98: $41,842; FY97- FY96-$55,103.
TITLE: Hormone Replacement Therapy
INSTITUTE: National Center for Health Statistics
P.I.: Dr. Kate Britt
INSTITUTION: N/A
GRANT NO.: N/A
KEYWORDS: menopause, postmenopausal, hormone replacement therapy HRT, osteoporosis, cardiovascular, oral estrogen, demography, vasomotor, urogenital, clinical
STUDY POP.: Women, menopausal, physicians
While the main indication for menopausal and postmenopausal, hormone replacement therapy (HRT) has been vasomotor and urogenital symptoms associated with menopause, use of HRT has also been found to reduce the incidence of osteoporosis and possible cardiovascular disease. These drugs are currently among the most commonly prescribed medications in the U.S., with 31.7 million prescriptions of oral menopausal estrogens dispensed in 1992. The goal of this project is to have information regarding the use of HRT as a nation, by various demographic characteristics (e.g., race, region, education) and characteristics of the providers (e.g., sex, specialty, practice type). Amount funded: $150,000.
TITLE: Preventive Hormone Therapy Decision Making on the World Wide Web
INSTITUTE: NIA
P.I.: Dr. Thomas Taylor
INSTITUTION: University of Washington
GRANT NO.: 2 RO1 AG1238104A1
KEYWORDS: hormone replacement therapy, post menopausal, HRT, behavior, web, clinical
STUDY POP.: Women, physicians
This project will extend prior work relating to physician practice and patient decisions regarding hormone replacement therapy (HRT). There are two major goals as follows: 1) development of a computerized decision support system that can be distributed over the world wide web and designed to assist women in their decisions regarding HRT, and 2) evaluation of the impact of the decision support aid on decisions that women make regarding HRT. Amount funded: $181,375.
TITLE: Study of Women's Health Across Nation: SWAN
INSTITUTE: NIA/NINR
P.I.: Dr. Sonia McKinlay, Coordinating Center P.I., Multiple sites and investigators
INSTITUTION: New England Research Institute
GRANT NO.: 1 UOI AG12553
KEYWORDS: menopause, aging, behavior, hormone replacement therapy, minorities, longitudinal, risk factors, disease, HRT, hysterectomy, oophorectomy, radiation, clinical
STUDY POP.: Women, peri- and menopausal, older African-American, Hispanic
This group of continuing research conducts a prospective, nation-wide, longitudinal study of the natural history of menopause, the effect of the perimenopausal transition on women's aging and subsequent susceptibility to disease, the decline of ovarian function in women. Special attention is given to women on estrogen therapy and other medical procedures such as hysterectomy/oophorectomy or radiation therapy. The study has several clinical sites and participating investigators. Awarded under RFA AG-94-002 (Menopause and Health in Aging Women). Amount funded: $350,000.
TITLE: Women with Schizophrenia and Substance Abuse
INSTITUTE: NIDA
P.I.: Dr. Jean Gearon
INSTITUTION: University of Maryland
GRANT NO.: 1 R29 DA11199 01A1
KEYWORDS: mental health, schizophrenia, substance abuse, co-occurring substance use, HIV, risk factors, violence, depression, behavior, clinical
STUDY POP.: Women
The primary goals of this project are: 1) to determine if women with schizophrenia and co-occurring substance use disorders are more vulnerable to HIV (e.g., engage in more high risk behaviors) and violent victimization than either women with major depression and co-occurring substance use disorders or women with substance use disorders only and no history of serious and persistent mental illness; 2) to determine if women with schizophrenia who abuse substances experience more violent victimization than women with major depression and co-occurring substance use disorders, or women with substance abuse disorders alone and no history of serious and persistent mental illness, and 3) to examine the causal sequencing between cognitive functioning, social competency, negative symptoms and HIV risk and victimization. Amount funded: $95,853.
TITLE: Sex and Structural Brain Abnormalities in Schizophrenia
INSTITUTE: NIMH
P.I.: Dr. Jill Goldstein
INSTITUTION: Harvard Institute for Psychiatry
GRANT NO.: 1 RO1MH56956 02
KEYWORDS: mental health, schizophrenia, brain, sexual dimorphism, gender differences, risk factors, MRI, clinical
STUDY POP.: Women and men, their families with schizophrenia
Although sex differences in the expression of schizophrenia have been reported, no study has attempted to explain these differences as a function of sexual dimorphism of the brain. This study will test the hypothesis that sex is a risk factor for brain abnormalities in schizophrenia by examining families with multiple ill members with MRI. Magnetic resonance images will be analyzed using a system that parses the entire brain into defined areas. Amount funded: $35,093.
TITLE: Estrogen-Induced Hippocampal Seizure Susceptibility
INSTITUTE: NINDS
P.I.: Dr. Catherine Woolley
INSTITUTION: Northwestern University
GRANT NO.: 1 R29 NS37324 01A1
KEYWORDS: neurology, epilepsy, seizure, hippocampus, estrogen, estradiol, menses, central nervous system, hormones, basic
STUDY POP.: Animal of epilepsy, (Female rats)
A significant proportion of women with epilepsy experience increased seizure frequency during phases of the menstrual cycle in which estradiol levels are elevated, termed catemenial epilepsy. Animal models of epilepsy also demonstrate that estradiol increases seizure susceptibility. Previous work in the adult female rat has shown that estradiol induces new dendritic spines and axospinous synapses on CA1 pyramidal cells in the hippocampus, a key brain structure in the generation and propagation of seizure activity. Estradiol-induced dendritic spines and synapses are correlated with increased excitability of hippocampal neurons and decreased hippocampal seizure threshold. This correlation suggests that estradiol-induced seizure susceptibility in women with catamenial epilepsy may be due, at least in part, to hormone-mediated alterations in hippocampal synaptic connectivity. These studies will use adult female rats to test the hypothesis that estradiol facilitates seizure activity through alteration of hippocampal synaptic structure and physiology. Amount funded: $70,000.
TITLE: Thermogenesis and Exercise in Lean and Obese Man
INSTITUTE: NIDDK
P.I.: Dr. Samuel Klein
INSTITUTION: Washington University
GRANT NO.: 2 RO1 DK37948
KEYWORDS: obesity, fat, metabolism, gender differences, insulin, hyperinsulinemia, exercise, fasting, % fat, clinical
STUDY POP.: Women and men
In general, women have more fat and store fat in different sites compared to men. Women also appear to differ with respect to the consequences of the fat, especially with respect to insulin sensitivity. This proposal is aimed at understanding sex differences in fat metabolism and in prevalence of obesity. It is hypothesized that physiological challenges of hyperinsulinemia, exercise and fasting will amplify sex differences. By studying groups of men and women who are matched for percent body fat, the investigators intent is to assess the independent effects of gender and adiposity on: 1) insulin action in different tissues (adipose tissue, liver skeletal muscle); 2) the metabolic responses to short-term fasting; 3) the metabolic response to endurance exercise. Amount funded: $165,000.
TITLE: The Differences in Skeletal Muscle Tissue Function in Differing Ethnic Groups
INSTITUTE: NIDDK
P.I.: Dr. Steve Heymsfield
INSTITUTION: Columbia University
GRANT NO.: P 30 DK 26687
KEYWORDS: obesity, skeletal muscle, muscle mass measurement, aging, chronic disease, MRI, clinical
STUDY POP.: Women, men, African-American, Caucasian, Asian, Hispanic
Loss of skeletal muscle mass is thought to play a central role in the functional limitation and disability that accompanies chronic disease states and aging. Muscle measurement methods are limited and inadequately validated. The current study is investigating conventional and developing new muscle mass measurement methods using state of the art body composition techniques. Magnetic resonance imaging, dual-energy absorptiometry, nuclear magnetic resonance spectroscopy, neuron activation analysis, and bioimpedance analysis are all being used to develop laboratory methods for measuring muscle mass in African American (n=125) and Caucasian (n=125) men and women between the ages of 20 and 90 years. This research will be expanded to include 75 Chinese and 75 Hispanic subjects. Amount funded: $97,995.
TITLE: Clinical and Experimental Study of Human Obesity
INSTITUTE: NIDDK
P.I.: Dr. Albert Stunkard
INSTITUTION: University of Pennsylvania
GRANT NO.: 2 RO1 DK56251 03
KEYWORDS: eating disorders, obesity, longitudinal, body size, fat percentage, risk factors, maternal obesity, clinical
STUDY POP.: Children
This project is a longitudinal study of 78 children, from 3-5 years of age, from either obese or non-obese mothers. The goal is to examine a group of variables related to food intake and energy expenditure along with measures of body size or composition, utilizing not only weight and length but measures of skinfold thickness and percent fat by dual energy x-ray absorptiometry, and body water, and isotope dilution measures. The study has already found that the two independent measures of energy intake at three (3) months of age predict body size and composition at 1 year of age and discounted the belief that a low total energy expenditure and maternal obesity predict body size and composition at 1 year of age. This study will continue to search for risk factors for obesity in the early childhood years. Amount funded: $100,000.
TITLE: The Role of Exercise in the Maintenance of Weight Loss in Obese Women
INSTITUTE: NIDDK
P.I. Jean Harvey Berino
INSTITUTION: University of Vermont
GRANT NO.: 1 R29 DK51517 01A1
KEYWORDS: eating disorders, obesity, weight maintenance, exercise, behavior, diet, clinical
STUDY POP.: Obese women
The aim of this project is to assess the mechanism by which exercise facilitates weight maintenance. A sample of 250-300 women aged 25-45 and 30-50 pounds over ideal body weight will be recruited to participate in a 24 week behavioral weight loss program that includes diet and exercise. Subjects will be followed for 12 months post-treatment and measures related to the hypothesized mechanisms of the effects of exercise will be assessed at 3 or 6 month intervals. Amount funded: $75,000.
TITLE: Uterine Pain - Mechanisms and Modulation
INSTITUTE: NINDS
P.I.: Dr. Ursula Wesselmann
INSTITUTION: Johns Hopkins University
GRANT NO.: 1 RO1 NS6553 01A1
KEYWORDS: pelvic pain, uterine pain, chronic pain, reproductive health, neurobiology, basic
STUDY POP.: Animal model (rat)
These studies will provide fundamental new information about the neuroanatomical and neurophysiological mechanisms of pelvic and uterine pain. An experimental model of uterine pain will be used to obtain information about the spinal pathways that process nociceptive afferent input from the uterus; assess the effects of peripheral opioid application on the spinal processing of nociceptive inputs from the uterus; and to determine the influence of the estrous cycle on spinal cord processing of noxious uterine stimulation. Amount funded: $130,000.
TITLE: Sex-specific genetic mediation of Pain and Analgesia
INSTITUTE: NIDR
P.I.: Dr. Jeffrey Mogil
INSTITUTION: University of Illinois at Urbana-Champaign
GRANT NO.: 1 RO1 DE12735 01
KEYWORDS: pain, analgesia, sex differences, non-opioid, pharmacology, genetics, basic
STUDY POP.: Animal model (mice)
Evidence suggests that quantitative sex differences in pain and analgesia may reflect the activation of qualitatively different pain modulatory systems in each sex. The investigators have provided pharmacological and genetic evidence supporting the contention that female mice possess a sex-specific, non-opioid analgesic mechanism. This project aims to examine three sex-specific gene effects. Testing will be done on additional genetic populations, including transgenic knock-out mice lacking functional expression of the Oprd1 gene. To characterize the female-specific analgesic mechanism, positional cloning of the female-specific chromosome 8 QTL will be done. Amount funded: $60,000.
TITLE: Sex Differences in Regional my-Opioid Receptor Pain Processing
INSTITUTE: NIDR
P.I.: Dr. Joh-Kar Zubieta
INSTITUTION: University of Michigan
GRANT NO. 1 RO1 DE12743 01
KEYWORDS: pain, opioid system, gender-specific, neurobiology, drugs, analgesia, PET, temporomandibular, clinical
STUDY POP.: Women and men
The goal of the proposed research is to describe and understanding of relevant aspects gender-specific neurobiology that occurs as the human undergoes chronic pain. The current proposal focuses on the opioid system, and specifically the µ opioid receptors, since these sites mediate many of the actions of exogenously administered antinociceptive drugs, as well as stress-and nociception-induced analgesia. This project will utilize position-emission tomography (PET) with a validated model of temporomandibular pain in a randomized, double blind, repeated measures, cross over design. Amount funded: $60,000.
TITLE: Pain and Analgesic Response: Sex and Hormone Variations
INSTITUTE: NIDR
P.I.: Dr. Sandra Comer
INSTITUTION: Research Foundation for Mental Hygiene
GRANT NO.: 1 RO1 DE12763 01
KEYWORDS: pain, gender differences, analgesia, menses, hormones, opioids, contraceptives, clinical
STUDY POP.: Women and men
The purpose of the project is to investigate sex differences in response to painful stimuli, specifically focusing on 1) the influence of gonadal hormones on pain responsivity and 2) the analgesic response to mu (morphine) and kappa (butorphanol) opioid agonists. Two pain procedures will be used: the cold pressor test, which combines sensory and emotional aspects of pain, and the mechanical pressure test, which can distinguish between sensory and emotional pain. Each study will compare normally cycling women to women on oral contraceptives and to men. Pain response will be measured at five different phases of the menstrual cycle (menstrual, follicular, evaluator, lutea, and late lutea.) Amount funded: $50,000.
TITLE: Opioid Systems: Sex- and Pregnancy- Linked Differences
INSTITUTE: NIDR
P.I.: Dr. Carrie Drake
INSTITUTION: Cornell University Medical College
GRANT NO.: 1 R29 DE12738 01
KEYWORDS: pain, analgesic, gender differences, pregnancy, opioids, analgesia, central nervous system, basic
STUDY POP.: Animal models (rat and guinea pig)
Two lines of evidence from human and animal studies suggest that drugs activating kappa opioid receptors (KOR) may be uniquely analgesic in women. KOR agonists have been shown to relieve post-surgical pain better in women than in men. Second, the well-documented increase in pain threshold during late pregnancy has been shown to involve KOR and their endogenous opioid ligand, dynorphin. The studies in this application are designed to test the hypotheses that 1) KOR are located on neurons involved in the modulation of pain transmission in the central nervous system; (CNS); 2) the greater responsiveness of females to KOR agonists is correlated with higher levels of KOR in nociception-related regions of the CNS in females; and 3) increases in KOR in spinal cord occur during late pregnancy. Amount funded: $50,000.
TITLE: Gender differences in P450 activities & their implication for in vivo drug interactions
INSTITUTE: FDA
P.I.: Dr. Robert A. Branch
INSTITUTION: University of Pittsburgh
GRANT NO.: N/A
KEYWORDS: gender differences, drugs, pharmacokinetics, cytochrome enzyme, clinical
STUDY POP.: Pre- and post-menopausal women and age-matched males
Pharmacokinetic studies are a requirement of the drug development process due to their potential to contribute to understanding drug metabolism and in leading to rational individualization of therapy. Six individual cytochrome P450 (CYP) enzymes in a single cocktail can be measured using the metabolism of a selective substrate for each enzyme. This study has been expanded to include increased numbers of pre and post-menopausal women to assess gender differences in the expression and regulation of individual CYP enzymes. Amount funded: $51,500.
TITLE: Variations in the drug-induced QT interval prolongation during the menstrual cycle and comparison to males.
INSTITUTE: FDA
P.I.: Dr. Ray Woosley
INSTITUTION: Georgetown University Medical Center
GRANT NO.: N/A
KEYWORDS: gender differences, cardiovascular, ventricular arrhythmia, drugs, hormones, menses, estradiol, clinical
STUDY POP.: Women and males, premenopausal
Women are more prone than men to develop Torsades de pointes ventricular arrhythmias during the administration of drugs that prolong cardiac repolarization. Women have slower cardiac repolarization that is expressed as longer QT intervals on the electrocardiogram (ECG). Animal studies have shown that sex hormones influence cardiac repolarization and potassium channel expression. During the menstrual cycle, there are dramatic changes in hormones (estradiol and progesterone) which may affect the response to drugs. The purpose of this project is to determine if there are differences in QT prolongation during the stages of the menstrual cycle after the administration of the antiarrhythmic drug, ibutilide. Another goal is to compare the QT response to ibutilide of women to men. Amount funded: $48,000.
TITLE: Pregnancy Labeling Testing
INSTITUTE: FDA
P.I.: Dr. Kit Aiken
INSTITUTION: The Center for Drug Evaluation and Research
GRANT NO.: N/A
KEYWORDS: pregnancy, prescription labels, physicians, clinical
STUDY POP.: Women and men, clinicians
This project will conduct focus testing in clinicians who prescribe medications for pregnant women. Primary care clinicians, such as obstetrician/gynecologists and family practice specialists, as well as maternal fetal specialists will be tested to determine if the drug labeling adequately identify risks. Amount funded: $25,000.
TITLE: Lymphangioleiomatosis (LAM):Patient Registry
INSTITUTE: NHLBI
P.I.: Intramural NWN-BI patient registry
INSTITUTION: Clinical Center, National Institutes of Health
GRANT NO.: N/A
KEYWORDS: LAM, rare diseases, pulmonary disease, reproductive health, registry, clinical
STUDY POP.: Women and men with LAM identified through NW Clinical Center
Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease of unknown etiology which occurs in women, primarily in their reproductive years. The goal of this is to establish a registry of individuals with LAM by forming a consortium of clinical centers and referring physicians who treat LAM patients. The cohort of identified individuals with LAM will be used to characterize the clinical features of subjects and provide information on the natural course of the disease. Lung tissue will be assessed to determine the molecular basis of LAM. The LAM registry tissue repository is maintained by the NIH Clinical Center with the assistance of ORWH, NHLBI, and ORRD. It serves as a resource for specimens of this rare condition that affects more women than men. Amount funded: $119,348.
TITLE: Fetal Neuroendocrinology, Parturition and the Myometrium
INSTITUTE: NICHD
P.I.: Dr. Peter W. Nathanielsz
INSTITUTION: Cornell University
GRANT NO.: 1 P01 HD 213S0 01
KEYWORDS: reproductive health, fetal neuroendocrinology, myometrium, parturition, pregnancy, premature labor, central nervous system, estrogen, basic
STUDY POP.: Animal model (primates-baboons), pregnant female
The goal of this project is to understand the mechanisms responsible for the onset of premature labor in humans. Project I will carry out studies in pregnant baboons and their fetuses to examine the regulation of fetal hypothalamo-pituitary-adrenal-placental loops and determine the critical regulatory mechanisms that drive the changes in estrogens. Amount funded: $142,161.
TITLE: Fetal Neuroendocrinology
INSTITUTE: NICHD
P.I.: Dr. Peter W. Nathanielsz
INSTITUTION: Cornell University
GRANT NO.: 3 PO1 HD21350 1052; 3 PO1 HD21350 0003; 3 PO1 HD21350 9003
KEYWORDS: neuroendocrinology, hypothalamic paraventricular nucleus, fetus, central nervous system, parturition, pregnancy, basic
STUDY POP.: Animal model (Sheep)
Studies in sheep have shown that the fetal hypothalamic paraventricular nucleus (PVN) is needed for the prolonged increase in the hypothalamic hypophyseal adrenal axis (HHAA) activity that lead to parturition. This research is examining the maturation and regulation of the fetal PVN and anterior pituitary using a combined molecular, cellular, and in vivo approach. They will by using a model of adolescent pregnant ewes which have been shown to carry growth retarded fetuses and to deliver prematurely. Amount funded: $150,000.
TITLE: HLA and Maternal/Placental Immune Function
INSTITUTE: NICHD
P.I.: Dr. Daniel Geraghty
INSTITUTION: Fred Hutchinson Cancer Research Center
GRANT NO.: 1 RO1 AI 38508 01
KEYWORDS: maternal/placental immune function, pregnancy, immunology, basic
STUDY POP.: Human tissue, female
This study will further investigate the expression of alternative HLA-G proteins and examine the unique roles that these proteins play in maternal-placental immune interaction. HLA-G protein expression in placental and maternal tissues and soluble G protein in maternal blood will be examined, emphasizing potential differences in abnormal pregnancies. The experimental plan will employ a combination of biochemical, molecular, and cellular approaches to examine the role of these molecules. The results of this study will enhance understanding of basic molecular mechanisms associated with the immune response during pregnancy, as it may relate to pregnancy outcomes. Amount funded: $28,122.
TITLE: HLA-G and Equivalent and Feto-Maternal Interaction
INSTITUTE: NICHD
P.I.: Dr. Hidde L. Ploegh
INSTITUTION: Massachusetts Institute of Technology
GRANT NO: 1 R01 AI38577 05
KEYWORDS: feto-maternal immune interaction, trophoblast genes, immunology, herpes, cytomegalovirus, pregnancy, abortion, viral infection, fetus, basic
STUDY POP.: Human cell culture
This study will examine feto-maternal interactions in the immune system mediated by the trophoblast-specific Class I gene products, HLA-G. Expression of HLA-G in cultured human trophoblast will be examined both under normal circumstances and in cells infected with Herpes Simplex Virus (HSV) or Cytomegalovirus (CMV). Each of these viruses down-modulates Class I expression in a unique manner, and has been associated with spontaneous abortion. This study will enhance understanding of the molecular basis of feto-maternal immune interactions and the effects of viral pathogens. Funded under Mechanisms of Maternal/Fetal Tolerance RFA.
TITLE: Fetal Trophoblasts Maintain Maternal Tolerance
INSTITUTE: NICHD
P.I.: Dr. John H. Russell
INSTITUTION: Washington University Medical School
GRANT NO.: 1 R01 AI38494
KEYWORDS: maternal tolerance, trophoblasts, pregnancy, immunology, tolerance, fetus, autoimmune, basic
STUDY POP.: Animal model (mice, Ipr and Gld mutants)
Maternal tolerance is critical during pregnancy, not only to prevent the initiation of an immunological response, but also to minimize the potential damage to the fetus. Maternal acceptance of the fetal allograft appears to be local, as it occurs without either general immunosuppression or specific tolerance to paternal antigens. A number of antigen-specific and antigen-independent models have been suggested to explain the tissue-specific acceptance of the fetus by the maternal immune system. This study will examine the role of the trophoblast in triggering antigen-dependent T cell death, using two mutant strains of mice (lpr and gld) deficient in this pathway. These mice are prone to autoimmune disease and have mutations in TNF proteins and receptors. The study will provide insights into basic mechanisms of maternal immunological tolerance to the fetus. Funded under Mechanisms of Maternal/Fetal Tolerance RFA.
TITLE: Decidual T Lymphocyte Phenotype and Function
INSTITUTE: NICHD
P.I.: Dr. Kent D. Heyborne
INSTITUTION: Swedish Medical Center
GRANT NO.: 1 R29 HD34079
KEYWORDS: maternal-fetal immune, T lymphocytes, infertility, immunology, miscarriage, pregnancy, preeclampsia, preterm birth, basic
STUDY POP.: Animal model (mouse)
Substantial evidence exists supporting a role for maternal-fetal immune interactions in mediating a wide variety of reproductive complications, including infertility, recurrent miscarriage, preeclampsia, intrauterine growth retardation, and preterm birth. This study will address the maternal-fetal immune relationship by examining phenotype and function of decidual T lymphocytes in a murine model. It will employ flow cytometry, immunohistochemistry, quantitative cDNA analysis, and hybridoma production of lymphocytes obtained from reproductive tissues at several points during gestation. The study will provide enhanced understanding of immunological mechanisms during pregnancy. Funded under Mechanisms of Maternal/Fetal Tolerance RFA
TITLE: Regulation of MHC Genes in the Trophoblast
INSTITUTE: NICHD
P.I.: Dr. Douglas F. Antczak
INSTITUTION: Cornell University
GRANT NO.: 1 R01 HD34086
KEYWORDS: pregnancy, trophoblast, immunology, MHC, endocrinology, basic
STUDY POP.: Animal model (horse)
This study will characterize the expression and regulation of MHC class I genes in the trophoblast of equids during early pregnancy. The horse was chosen as experimental model because its trophoblast shows many morphological and endocrinological similarities to that of humans. In addition, the form and time course of placental development in equids allows a clarity of in vivo and in vitro investigations of immunological questions not found in other animal models. The study will examine different aspects of MHC gene expression and regulation using 3 distinct populations of equine trophoblasts. Funded under Mechanisms of Maternal/Fetal Tolerance RFA.
TITLE: A Primate Model of Human Maternal-Fetal Immune Tolerance
INSTITUTE: NICHD
P.I.: Dr. Thaddeus G. Golos
INSTITUTION: University of Wisconsin
GRANT NO.: 1 R01 HD34215 01
KEYWORDS: pregnancy, maternal-fetal tolerance, trophoblasts, placenta, MHC, immunology, basic
STUDY POP.: Animal model (primate-Rhesus monkey), cell culture
Because the structural and functional organization of the placenta, the physiology of pregnancy, and the MHC of primates is unique, the nonhuman primate represents a highly appropriate model to study maternal recognition and immunological tolerance during pregnancy. This study will examine the expression of nonpolymorphic MHC class I molecules on the Rhesus monkey placenta, and the expression of an HLA-G-like mRNA in placental tissue and cultured trophoblasts. This study will yield important information about immunological mechanisms during pregnancy. Funded under Mechanisms of Maternal/Fetal Tolerance RFA.
TITLE: HLA-G Peptides in Immune Tolerance
INSTITUTE: NICHD
P.I.: Dr. Carol Clayberger
INSTITUTION: Stanford University School of Medicine
GRANT NO.: 1 R01 HD34214 01
KEYWORDS: pregnancy, maternal-fetal, immune response, tolerance, trophoblasts, MHC, fetus, immunology, molecular, basic
STUDY POP.: Animal model (rodent)
The unique pattern of class I major histocompatibility complex (MHC) antigen expression at the maternal/fetal interface is believed to play a major role in protecting the fetus from rejection by the mother's immune system. Trophoblasts, the only fetal tissue that comes into direct contact with the mother, do not express polymorphic class I and II MHC antigens. This may, in part, explain the lack of maternal immune response against the fetus. Recently, a non-classical MHC molecule, designated HLA-G, was found to be present on certain subpopulations of trophoblasts, suggesting that the expression of this non-polymorphic MHC molecule may play an active role in maternal/fetal tolerance. This study will examine the molecular mechanisms by which soluble HLA-G peptides induce unresponsiveness and to investigate their role in pregnancy. Funded under Mechanisms of Maternal/Fetal Tolerance RFA.
TITLE: A Prospective Observation Study Evaluating Obstetric Outcomes in Women with the Factor V Leiden Mutation (Multicenter Network of Maternal-Fetal Medicine Units)
INSTITUTE: NICHD
P.I.: Dr. Michael Varner
INSTITUTION: University of Utah
GRANT NO.: 5 U10 HD 34208-03
KEYWORDS: pregnancy, thrombosis, factor V Leiden mutation, embolism, oral contraceptives, fetus, maternal, clinical
STUDY POP.: Women, African-American, Caucasian
Thromboembolism, albeit an uncommon event, remains the number one cause of maternal mortality in both the African-American and Caucasian populations in the U.S. Women who carry the factor V Leiden mutation are at increased risk of developing a deep venous thrombosis during pregnancy, or during oral contraceptive usage. The goals of this project are to 1) evaluate the incidence of the factor V Leiden mutation in an ethnically diverse unselected obstetric population, 2) follow obstetric outcomes in women identified as carriers of the factor V Leiden mutation, and 3) determine if outcome is different if only mother carries the factor V Leiden mutation compared to if both the mother and fetus carry the mutation. Amount funded: $406,170.
TITLE: Mechanisms of Persistent Temporomandibular Pain.
INSTITUTE: NIDR
P.I.: Dr. Ke Ren
INSTITUTION: University of Maryland
GRANT NO.: 1 R01 DE11964 01
KEYWORDS: temporomandibular disorders, pain, inflammation, central nervous system, basic
STUDY POP.: Animal model (rat)
Innovative use of an animal (rat) model will investigate the hypothesis that orofacial deep tissue injury leads to a cascade of events resulting in functional changes in the brain. These changes are associated with temporomandibular joint (TMJ) pain and hyperalgesia. Inflammation of the TMJ or perioral skin will be examined to determine effects of injury on hyperalgesia and neuronal plasticity in the medullary dorsal horn. Funded under RFA DE-95-002.
TITLE: Inflammatory Mediators in Masticatory Muscles.
INSTITUTE: NIDR
P.I.: Dr. Grace K. Pavlath
INSTITUTION: Emory University
GRANT NO: R01 DE11987 01
KEYWORDS: temporomandibular disorders, masseter, sex hormones, cytokines, inflammation, basic
STUDY POP.: Animal model (mouse)
This research proposes to investigate the roles of cytokine protein and inflammatory peptides in the etiology of response to trauma. Using a mouse model, the study hypothesizes that male and female sex hormones differentially affect the response of the masseter muscle to injury and inflammation. Funded under RFA DE-95-002.
TITLE: Modulation of TMJ Degredation by Relaxin and Estrogen.
INSTITUTE: NIDR
P.I.: Dr. Sunil D. Kapila
INSTITUTION: University of California at San Francisco
GRANT NO.: 1 R29 DE11993 01
KEYWORDS: temporomandibular disorders, estrogen, relaxin, hormones, basic
STUDY POP.: Animal model (rabbit), arthritic
Estrogen and relaxin are hypothesized as pathogenic factors in TMJ changes. Studies using an experimental arthritis rabbit model, will test the possible synergistic effects of these hormones on joint disc and/or TMJ associated ligament cells. Funded under RFA DE-95-002.
TITLE: TMJ Function and Mechanics: Experimental Models.
INSTITUTE: NIDR
P.I.: Dr. Susan W. Herring
INSTITUTION: University of Washington
GRANT NO.: 1 R01 DE11962-01
KEYWORDS: temporomandibular disorders, gender differences, aging
STUDY POP.: Animal model (pig)
A series of investigations is proposed to more fully characterize an animal model (the miniature pig) for TMJ biomechanics. A related goal is to link TMJ biology (anatomy, physiology, kinematics, and cell biology) with computer-based modeling of the masticatory system. Age and gender differences in the role of capsular ligaments in condylar stability will be addressed. Funded under RFA DE-95-002.
TITLE: Defining the Function of Engrailed-2.
INSTITUTE: NIDR
P.I.: Dr. David Sassoon
INSTITUTION: Mount Sinai School of Medicine
GRANT NO: 1 R01 DE11953-01
KEYWORDS: temporomandibular disorders, engrailed-2 molecule, molecular, gene expression, basic
STUDY POP.: Animal model (Transgenic mice)
The long-term goals of this research are to understand how positional identity of skeletal muscles is established and how jaw muscles are specified and maintained, with a focus on the roles of the Engrailed-2 molecule. The investigator proposes to molecularly dissect the En-2 enhancer with reporter gene constructs in transgenic mice and to determine the human regulatory elements to aid in identifying sites underlying jaw-specific En-2 expression. Funded under RFA DE-95-002.
TITLE: Brain Stem Mechanisms of TMDS Pain.
INSTITUTE: NHLBI
INSTITUTE: NIDR
P.I.: Dr. James Hu
INSTITUTION: University of Toronto
GRANT NO: 1 R01 DE11995-01
KEYWORDS: temporomandibular disorders, TMJ inflammation, central nervous system, molecular, pain
STUDY POP.: N/A
The investigative team in this proposal will examine the central nervous system adaptive responses to TMJ inflammation at the molecular and physiological level. Prior studies support the utility of measuring EMG responses to mustard oil injection into the TMJ as a measure of nociception. The project has potential to provide new information on trigeminal neural mechanisms that mediate pain originating from the TMJ. Funded under RFA DE-95-002.
TITLE: Sex-Related Opiate and Autonomic Mechanisms in TMD Pain
INSTITUTE: NIDR
P.I.: Dr. David Bereiter
INSTITUTION: Rhode Island Hospital
GRANT NO.: 1 RO1 DE12758 01
KEYWORDS: pain, temporomandibular disorders TMD, efferent nerves, TMJ, basic
STUDY POP.: Animal model (rat)
Temporomandibular disorders (TMD) refer to a family of conditions that cause pain of the temporomandibular joint (TMJ) region and surrounding deep craniofacial muscles. The proposed studies use an animal model to selectively activate small diameter afferent nerves to examine the properties of second-order neurons that receive noxious sensory input from the TMJ region in anesthetized male and female rats. The specific aims will examine the effects of the well-known activators of endogenous pain control systems, morphine and vagal afferent nerve activity, to assess the properties of TMJ-responsive neurons. Amount funded: $50,000.
TITLE: Health Promotion for Women with Physical Disabilities
INSTITUTE: NICHD
P.I.: Dr. Margaret A. Nosek
INSTITUTION: Baylor College of Medicine
GRANT NO: R01 HD35051
KEYWORDS: disabilities, impairment, survey, behavior, clinical
STUDY POP.: Women
Based on results from a recent national survey on women with physical disabilities, the investigators will to develop and test a model wellness action program for a sample of 400 women with a range of disabilities and severity of impairment. The research is based on current scientific approaches to promote behavior change through individualized goal setting, peer support, and enhanced self-efficacy. Amount funded in FY98 is RFA HD-96-002.
TITLE: Health Promotion Intervention for Women with MS.
INSTITUTE: NICHD
P.I.: Dr. Alexa Stuifbergen
INSTITUTION: University of Texas School of Nursing
GRANT NO.: R01 HD35047
KEYWORDS: multiple sclerosis, MS, disabilities, impairment
STUDY POP.: Women
A sample of 150 women with MS will be recruited to participate in a randomized clinical study to determine effects of an eight week health promotion intervention. The study's final objectives are to determine how women with MS can benefit from a program tailored to their limitations and contribute to continued independent living. Amount funded in FY98 is RFA HD-96-002.
TITLE: Wellness for Women with Polio: A Holistic Program Model.
INSTITUTE: NICHD
P.I.: Dr. Denise Tate
INSTITUTION: University of Michigan
GRANT NO.: R01 HD35053
KEYWORDS: disability, neuromuscular mobility impairment, polio, behavior, diet, quality of life, behavior, fatigue, clinical
STUDY POP.: Women
Using a case-control design, this grant will structure a wellness program for women with chronic neuromuscular mobility impairments. The 200 subjects, women between 41 and 65, allow measurement of the program's impact on nutritional intake, fatigue, and quality of life. Amount funded in FY98 is RFA HD-96-002.
Content revised: 7/14/99
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