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Biomedical subjects

T N Brown

Publications and source records attributed to T N Brown.

7 recordsLinked to original sources
PubMed2001

Are risk and protective factors for substance use consistent across historical time?: national data from the high school classes of 1976 through 1997.

Researchers have seldom examined whether risk and protective factors are consistently linked to substance use across historical time. Using nationally representative data collected from 22 consecutive cohorts of high school seniors (approximate N = 188,000) from the Monitoring the Future (MTF) project, we investigated whether correlates of substance use changed across historical time. We found a high degree of consistency across historical time in predictors of past month cigarette use, past month alcohol use, past year marijuana use, and past year cocaine use. Some predictors such as religiosity, political beliefs, truancy, and frequent evenings out were consistently linked to substance use. The consistency of other predictors such as region, parental education, and college plans was contingent in part upon historical time period, the particular substance, and its level of use.

Adolescent↗
PubMed2000

A c-fos/Estrogen receptor fusion protein promotes cell cycle progression and proliferation of human cancer cell lines.

c-fos is the prototypic member of a family of transcription factors that regulate many cellular processes, including proliferation. c-fos heterodimerizes with jun family members to form the AP-1 transcription factor complex which binds specific DNA recognition elements in the promoters of many genes. Following rapid induction in response to serum or growth factors, c-fos regulates expression of downstream target genes involved in cellular proliferation. Although much work has focused on activation of cell cycle regulatory genes by c-fos, less is known about negative regulation of gene expression by this transcription factor. The cyclin-dependent kinase (cdk) inhibitor p21(Cip1/WAF1) is a negative regulator of cdk activity, thereby impeding cell cycle progression. By sequence analysis, we identified a putative AP-1 element in the p21(Cip1/WAF1) promoter. To investigate how this site regulated p21(Cip1/WAF1) expression and mitigate external effects on c-fos expression, we used a c-fos/estrogen receptor (c-fosER) fusion construct in which this transcription factor is conditionally activated by estradiol. In the presence of estradiol, c-fosER downregulated p21(Cip1/WAF1) promoter activity. This inhibition was dependent on the putative AP-1 site. Activation of c-fosER induced cell cycle progression and proliferation in a manner similar to serum stimulation. We concluded that activation of c-fosER mediated transcriptional inhibition of p21(Cip1/WAF1) through a previously uncharacterized AP-1 site, revealing an important role for c-fos in negative control of cell cycle regulatory genes.

Cell Cycle↗
PubMed1999

Transcriptional inhibition of matrix metalloproteinase 9 (MMP-9) activity by a c-fos/estrogen receptor fusion protein is mediated by the proximal AP-1 site of the MMP-9 promoter and correlates with reduced tumor cell invasion.

Tumor cell invasion of basement membranes is one of the hallmarks of malignant transformation. Tumor cells secrete proteolytic enzymes known as matrix metalloproteinases (MMPs) which degrade extracellular matrix molecules. Increased expression of MMP-9 has been associated with acquisition of invasive phenotype in many tumors. However, multiple mechanisms for regulation of MMP-9 gene expression by tumor cell lines have been proposed. A number of transcription factor binding sites have been characterized in the upstream regulatory region of the MMP-9 gene, including those for AP-1. To determine how a specific AP-1 family member, c-fos, regulates MMP-9 promoter activity through these sites, we used an expression vector containing the c-fos coding region fused to the estrogen receptor (ER) ligand binding domain. This construct is activated upon binding estradiol. Stable expression of this construct in ER negative squamous cell carcinoma (SCC) lines produced an estradiol dependent decrease in the number of cells that migrated through a reconstituted basement membrane. This decreased invasiveness was accompanied by estradiol dependent downregulation of MMP-9 activity as determined by gelatin zymography. Estradiol also produced transcriptional downregulation of an MMP-9 promoter construct in cells transiently transfected with the c-fosER expression vector. This downregulation was mediated by the AP-1 site at -79 bp in the MMP-9 promoter. We concluded that the proximal AP-1 site mediated the transcriptional downregulation of the MMP-9 promoter by a conditionally activated c-fos fusion protein.

Binding Sites↗
PubMed1985

Documenting workload to better integrate clinical and distributive services.

Use of workload and work-flow documentation in two pharmacy satellites to evaluate pharmacists' productivity is described. Workload was evaluated during 14 consecutive days in May 1983 and 7 consecutive days in May 1984. All pharmacists and technicians working in the satellites recorded times for their activities on a form that listed every possible activity; interruptions such as answering the telephone, responding to walking requests, replacing stock, and lunches and break times were also recorded. Concurrently, the clinical coordinator observed and evaluated work performed for four-hour time blocks at least once each day. Analysis of workload and work-flow information identified problems with scheduling, priorities, interruptions, and pharmacists' knowledge of clinical pharmacy practice. Based on these observations, the following changes were implemented: pharmacists were scheduled to work either inside or outside the satellites for two-week or one-month time periods, priorities were assigned to certain tasks performed inside or outside the satellites, job assignments were made based on the pharmacist's capabilities and the needs of the patient-care areas, a form for documenting potential problem orders was created, and pharmacists were evaluated monthly and given one-on-one instruction by the clinical coordinator. Documentation of time use identified problems and led to changes in assignments that better integrated clinical, educational, and distributive responsibilities for the purpose of providing more efficient and effective services.

Appointments and Schedules↗
PubMed1983

Stress urinary incontinence: a simple and practical approach to diagnosis and treatment.

A study to evaluate the efficacy of a simple and inexpensive diagnostic and therapeutic approach to stress incontinence in 46 elderly women is described. The treatment had two aspects: estrogens, both orally and topically, and a pelvic floor exercise program. The study shows that stress incontinence and stress incontinence with urgency incontinence in non-institutionalized, ambulant elderly women can be diagnosed and successfully treated in the great majority of cases without the need for expensive and potentially hazardous diagnostic and therapeutic modalities.

Adult↗
PubMedDate not supplied

Racism and the physical and mental health status of African Americans: a thirteen year national panel study.

This paper examined the relationships between the experiences and perceptions of racism and the physical and mental health status of African Americans. The study was based upon thirteen year (1979 to 1992), four wave, national panel data (n = 623) from the National Survey of Black Americans. Personal experiences of racism were found to have both adverse and salubrious immediate and cumulative effects on the physical and mental well-being of African Americans. In 1979-80, reports of poor treatment due to race were inversely related to subjective well-being and positively associated with the number of reported physical health problems. Reports of negative racial encounters over the 13-year period were weakly predictive of poor subjective well-being in 1992. A more general measure of racial beliefs, perceiving that whites want to keep blacks down, was found to be related to poorer physical health in 1979-80, better physical health in 1992, and predicted increased psychological distress, as well as, lower levels of subjective well-being in 1992. In conclusion, the authors suggested future research on possible factors contributing to the relationship between racism and health status among African Americans.

Adaptation, Psychological↗