PubMed Health⌕ Search

Biomedical subjects

Jeanne Y Wei

Publications and source records attributed to Jeanne Y Wei.

10 recordsLinked to original sources
PubMed2006

Maintaining serum response factor activity in the older heart equal to that of the young adult is associated with better cardiac response to isoproterenol stress.

To understand the effect of transcription regulation in modulating cardiac aging, we sought to study the role of serum response factor (SRF), a key transcription factor in the heart that is normally increased with senescence and also in congestive heart failure. A Tet-Off gene expression system was used for cardiac-specific over-expression of a mutant SRF protein. In these binary transgenic mice, there is no age-related increase in SRF protein expression; in fact, there appeared to be a mild reduction of SRF protein (Mild-R SRF Tg). The older, middle-aged (15 mo) Mild-R SRF Tg mice appeared healthier and were better able to maintain their left ventricular systolic pressure (LVSP) in response to moderate â-adrenergic stimulation compared with age-matched Non-Tg mice, which demonstrated a negative ionotropic response. The Mild-R SRF Tg hearts had lower mRNA expression of BNP (p < 0.05), and the sodium calcium exchanger (p < 0.05), compared to Non-Tg. Mild-R SRF Tg had higher mRNA levels of SERCA2 (p < 0.05) and ryanodine receptor 2 (p < 0.05) compared to Non-Tg hearts. These findings suggest that preventing the age-associated increase in SRF is associated with better preserved intracellular calcium handling and functional response to stress; it might be advantageous for the older adult heart. This mouse model could be helpful in elucidating the molecular mechanisms underlying certain age-related changes in cardiac reserve capacity and response to stress.

Age Factors↗
PubMed2006

Zipzap/p200 is a novel zinc finger protein contributing to cardiac gene regulation.

Serum response factor (SRF) plays an important role in the regulation of immediate-early genes and muscle-specific genes, while SRF cofactors may contribute significantly to assist in tissue-specific, development-stage related regulation of SRF-target genes. We recently cloned a novel SRF cofactor, termed zipzap/p200, which is a zinc finger protein yet to be characterized. We determined that zipzap/p200 is a 200-kDa protein with two classic C2H2 zinc fingers at the carboxyl terminus where the nucleotide sequence was highly conserved among human, mouse, and rat. The zipzap gene was expressed in multiple tissues and at multiple ages, including the fetal and adult heart. The zipzap protein interacted with SRF in vivo and was found in protein complexes containing SRF and other SRF cofactors, including p49/strap and Nkx2.5. Zipzap/p200 activated the promoter of cardiac genes and potentiated the effect of myocardin on ANF promoter activity. Therefore, zipzap may serve as a transcription co-activator for the regulation of cardiac gene expression. Our data support the notion that a number of SRF cofactors may participate in gene regulation and thereby contribute to the delicate control of gene expression in complex biological processes.

Adult↗
PubMed2006

Assessment of medication management by community-living elderly persons with two standardized assessment tools: a cross-sectional study.

BACKGROUND: The ability of patients to adhere to a medication regimen is imperative for achieving optimal outcomes. Elderly patients, especially those with memory loss, should be evaluated for their ability to manage medications to prevent significant drug-related problems. Assessment tools to determine the ability to manage medication therapy have not been tested in elderly patients with cognitive impairment. OBJECTIVES: This study compared the Medication Management Ability Assessment (M1V1AA) and the Drug Regimen Unassisted Grading Scale (DRUGS) as standardized tools to assess medication management skills in elderly patients with a range of cognitive function and evaluated the association between the results obtained from these scales and self-reported drug-related problems. METHODS: This was a cross-sectional study of older individuals living in the community. At a scheduled study visit, the research assistant (RA) questioned participants with a structured interview to document demographic information, medical history, prescription use, over-the-counter drug and dietary supplement use, health care resource use, medication management practices, and adverse drug events. Cognitive status was assessed with the Mini-Mental State Examination (MMSE) and functional status with the instrumental activities of daily living rating scale. The MMAA, which uses a fictitious medication regimen with labeled prescription bottles, and the DRUGS, which uses the patient's own prescription bottles, were administered. Three months after the visit, the RA telephoned participants to determine recent changes in living situation and drug-related problems. RESULTS: The study group comprised 52 people with a mean (SD) MMSE score of 28.3 (2.5). The participants had a mean (SD) age of 75.8 (6.2) years; 69% (36/52) were women, and 96% (50/52) were white. Participants reported an average of 4.1 medical conditions, and 88% (46/52) reported good to excellent health. Skipping doses or cutting them in half was reported by 25% (13/52) of participants who adjusted doses themselves. Almost half (44%) reported medication problems and/or medication ineffectiveness during the past 3 months at both the study visit and the 3-month follow-up (23/52 for both). The 49 participants who took the MMAA had a mean (SD) score of 19.4 (6.1), with a range of 0 to 25. Of the 49 participants with scores, 34 took less than the correct number of tablets and 13 took more. The 46 participants who took the DRUGS had a mean (SD) score of 91.6 (24.7), with a range of 0 to 100. Forty of 46 participants attempting the test attained the maximum score. Higher scores for both tests indicate better accuracy. Analysis revealed that the MMAA and the DRUGS correlated with one another (P = 0.000). We found no significant associations between these medication management assessment tools and selfreported adherence or drug-related events. CONCLUSIONS: The MMAA and DRUGS tools correlated positively with cognitive function in this population of community-living elderly persons but need further evaluation of their ability to predict who is at greatest risk for drug related problems due to nonadherence to medication regimens.

Aged↗
PubMed2006

Nutrition and cardiac cachexia.

PURPOSE OF REVIEW: Congestive heart failure is a leading cause of morbidity and mortality, especially in older persons. In advanced stages of the disease, congestive heart failure can be associated with serious complications such as cardiac cachexia (defined here as weight loss of more than 6% in 6 months). This review will discuss recent insights into the pathophysiology, anthropometric predictors and potential management of cardiac cachexia. RECENT FINDINGS: Cardiac cachexia and the associated progressive weight loss are sometimes overlooked by care providers. A delay in diagnosis often results in further loss of vital tissues, progressive weakness, fall-related injuries and potentially long-term care institutionalization and/or death. Emerging data suggest that congestive heart failure is a dynamic disorder of many organ systems, including the myocardial, neurohormonal, immune, vascular, gastrointestinal, renal and musculoskeletal systems. It is becoming more widely appreciated that it is the deterioration of this interactive multisystem complex that results in the systemic inflammation and progressive wasting and atrophy of muscle and other organ tissues, which is the hallmark of cardiac cachexia. SUMMARY: Cardiac cachexia in congestive heart failure patients may be associated with a low level of physical activity. A high systemic inflammatory state is another marker of cardiac cachexia. Prudent anti-inflammatory nutrition, dietary supplements and exercise can serve to ameliorate and/or potentially prevent progressive wasting. A better understanding of factors contributing to the development of cardiac cachexia will enable us to design preventive strategies and provide improved care for individuals with this debilitating condition.

Aged↗
PubMed2004

Identification of a novel serum response factor cofactor in cardiac gene regulation.

The transcription factor serum response factor (SRF) plays an important role in the regulation of a variety of cardiac genes during development and during adult aging. A novel SRF cofactor, herein called p49/STRAP, for SRF-dependent transcription regulation-associated protein, was recently identified in our laboratory. This protein interacted mainly with the transcriptional activation domain of the SRF protein and was found to bind to SRF or to the complex of SRF and another cofactor, such as myocardin or Nkx2.5. The expression of p49/STRAP affected the promoter activity of SRF target genes in a non-uniform manner. For example, p49 activated MLC2v and cardiac actin promoters when it was co-transfected with SRF, but it repressed atrial natriuretic factor promoter activity, which was strongly induced by myocardin. The p49/STRAP mRNA was observed to be highly expressed in fetal, adult, and senescent human hearts, and also in hearts of young adult and old mice, suggesting that p49/STRAP may be an important SRF cofactor in the transcriptional regulation of mammalian cardiac muscle genes throughout the life span.

Actins↗
PubMed2003

Expression of bcl-2 protein is associated with shorter survival in nonsmall cell lung carcinoma.

BACKGROUND: The aim of this study was to assess the relationship between the expression of the 27-kilodalton (kD) bcl-2 protein and survival among nonsmall cell lung carcinoma (NSCLC) patients. METHODS: Paired tissue samples of histologically confirmed tumor and uninvolved lung of 91 randomly selected NSCLC patients were used in this study. The expression of 27-kD bcl-2 proteins in uninvolved lung and tumor tissue specimens was analyzed using Western blot analysis. Overall survival was estimated using the Kaplan-Meier method. The relation between patient survival and expression of the 27-kD bcl-2 protein in uninvolved lung, tumor, and in uninvolved lung and/or tumor tissue specimens was assessed using log-rank tests and Cox proportional hazards multiple regression. RESULTS: The 27-kD bcl-2 protein was expressed in 54% of the uninvolved lung tissue specimens, in 53% of the tumor tissue specimens, and in 70% of the uninvolved lung and/or tumor tissue specimens. When NSCLC patient survival was considered with respect to the expression of the 27-kD bcl-2 protein, a statistically significant shorter survival was observed for patients whose tissue samples expressed the 27-kD bcl-2 protein in the uninvolved lung and in the uninvolved lung and/or tumor (log-rank test, P = 0.008 and P = 0.001, respectively). Cox proportional hazards multiple regression models also showed statistically significant associations between shorter survival and positive 27-kD protein expression in the uninvolved lung (hazard ratio of 2.27; P = 0.05) and in the uninvolved lung and/or tumor (hazard ratio of 5.58, P = 0.008) after controlling for tumor size, stage, the type of surgery received, smoking status, age, and cell type. CONCLUSIONS: In the current study, patients with nonsmall cell lung carcinoma with positive expression of the 27-kD protein bcl-2, either in the uninvolved lung or in uninvolved lung and/or tumor, were found to have significantly poorer postresection survival.

Aged↗
PubMed2003

Model of functional cardiac aging: young adult mice with mild overexpression of serum response factor.

Serum response factor (SRF) is an important transcription factor that may have a role in the maintenance of cardiac structure and function. The level of SRF mRNA expression increases approximately 16% in the hearts of mice during adult aging. To model the effect of mild SRF elevation in the aging heart, transgenic mice with low levels of SRF overexpression were generated. By 6 mo of age, the transgenic mice had a 19% increase of heart-to-body weight ratio compared with nontransgenic mice. In addition, they had a 12% increase in myocyte size, a 6.7% increase in collagen deposition, and altered gene expression of a number of muscle-specific and cardiac genes. Doppler echocardiography revealed that these transgenic mice had increased left ventricular wall thickness and decreased left ventricular (LV) volumes, increased LV stiffness with 20% reduction in early diastolic LV filling (peak E), and 35% decline in peak E-to-peak A (late diastolic filling) ratio. The observed changes, especially those in the E/A ratio, are similar to those seen clinically in late life as a part of human adult myocardial aging.

Aging↗
PubMed2002

Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues.

Using single-cell sequence analysis, we discovered that a high proportion of cells in tissues as diverse as buccal epithelium and heart muscle contain high proportions of clonal mutant mtDNA expanded from single initial mutant mtDNA molecules. We demonstrate that intracellular clonal expansion of somatic point mutations is a common event in normal human tissues. This finding implies efficient homogenization of mitochondrial genomes within individual cells. Significant qualitative differences observed between the spectra of clonally expanded mutations in proliferating epithelial cells and postmitotic cardiomyocytes suggest, however, that either the processes generating these mutations or mechanisms driving them to homoplasmy are likely to be fundamentally different between the two tissues. Furthermore, the ability of somatic mtDNA mutations to expand (required for their phenotypic expression), as well as their apparently high incidence, reinforces the possibility that these mutations may be involved actively in various physiological processes such as aging and degenerative disease. The abundance of clonally expanded point mutations in individual cells of normal tissues also suggests that the recently discovered accumulation of mtDNA mutations in tumors may be explained by processes that are similar or identical to those operating in the normal tissue.

Adult↗
PubMed2002

Estrogen therapy and noncognitive psychiatric signs and symptoms in elderly patients with dementia.

OBJECTIVE: This study investigated the efficacy and safety of short-term estrogen therapy in decreasing noncognitive signs and symptoms of dementia in demented elderly patients. METHOD: Sixteen moderately to severely demented elderly patients with aggressive behavioral disturbances were randomly assigned to receive conjugated equine estrogens or placebo in a 4-week clinical trial. Frequency and severity of noncognitive signs and symptoms of dementia, as assessed with the Dementia Signs and Symptoms Scale, were compared between estrogen and placebo groups. Data were analyzed with intent-to-treat and regression modeling methods. RESULTS: Estrogen therapy was associated with a significantly greater improvement on the Dementia Signs and Symptoms Scale total score than placebo. All five Dementia Signs and Symptoms Scale subscale comparisons favored estrogen therapy. No adverse effects were observed. CONCLUSIONS: These preliminary data suggest that short-term estrogen therapy may safely decrease the frequency and severity of noncognitive signs and symptoms of dementia in elderly patients.

Age Factors↗