T'ai Chi Chih as an intervention for heart failure.

A program of T'ai Chi Chih, a modified T'ai Chi exercise, was piloted in a study comprised of a small sample of individuals with heart failure. A conceptual framework guided the study design, integrating theories of the neurohormonal dynamics of heart failure with mind-body holistic perspectives of health. Comparisons of pre- and post-measures of heart failure symptoms, general health, mental health, functional capacity, and energy perceptions support the potential of T'ai Chi Chih in managing heart failure symptoms and improving quality of life. In this article, quantitative interviews capture the meaning of experiencing a complementary therapy as an intervention for chronic illness. Participation in T'ai Chi Chih by individuals with heart failure is a cost-effective, noninvasive alternative strategy that warrants continued investigation.

The energy costs of a modified form of T'ai Chi exercise.

BACKGROUND: Alternative strategies for exercises that provide both training and relaxation benefits are optimal for persons with very low functional capacities who also are at high risk for complications. T'ai Chi C'hih, a modified form of traditional T'ai Chi, is a series of slow balanced movements and breathing promoted to increase energy levels and induce relaxation. OBJECTIVES: To estimate the energy costs and cardiovascular effects of T'ai Chi C'hih. Measured energy costs of specific activities can assist with safe exercise prescription for individuals with very low energy reserves. METHODS: A convenience sample (n = 26) of healthy adults participated in this study, which involved completion of surveys to estimate functional capacity and exercise participation, training in a select series of nine T'ai Chi C'hih movements, and oxygen consumption testing while movements are performed. Movements involving front to back and lateral moves of the lower extremity, full shoulder range of motion of upper extremity, and deep forced inhalation and stepped exhalations were performed at slow to fast cadences in sitting and standing positions. The Human Activity Profile was used to estimate lifestyle energy consumption. Exercise participation was quantified as Kcal/Kg(1) expended per week. RESULTS: Metabolic equivalents (METs) for sitting T'ai Chi C'hih movements were estimated to be 1.5 +/- 0.17 and 2.3 +/- 0.34 for slow standing, and 2.6 +/- 0.47 for fast standing. Mean maximum heart rates ranged from 43% to 49% of predicted maximum heart rates. Mean increases in both systolic and diastolic blood pressures over resting were 8%. Mean METs of breathing exercises ranged from 3 to 3.6. There were no differences in responses to the movements by gender or experience with T'ai Chi exercise. CONCLUSION: The movements used to perform T'ai Chi C'hih require energy expenditure comparable with that for activities of daily living and for low level exercises currently recommended for persons with low exercise tolerance. Therefore, T'ai Chi C'hih may be an alternative approach to health promotion in many populations with chronic disease.

Neo-adjuvant chemotherapy for operable breast cancer induces apoptosis.

The use of neo-adjuvant chemotherapy (often referred to as pre-operative or primary chemotherapy) represents a major change in the management of breast cancer as a systemic disease. Laboratory studies have shown that many anti-cancer agents with differing modes of action achieve cytotoxic effects by inducing apoptosis. In this study, we investigated the induction of apoptosis by neo-adjuvant chemotherapy in human breast cancer. The aim was to determine whether a correlation existed between post chemotherapy apoptotic index (AI) and clinical response and patients' survival. Our results indicate that apoptosis is induced by neo-adjuvant chemotherapy and that the response is variable. Our data show that post chemotherapy AI correlated with clinical response and increased patient survival, including both relapse (disease) free survival and overall survival. Post-neo-adjuvant chemotherapy AI levels in primary breast cancer may possibly predict an individual patient's overall response.

An exploratory study of developmental growth in adults with heart failure.

Persons with heart failure face a myriad of challenges due to the physical limitations imposed by the chronic illness. Despite these changes, each person must continue to face the developmental challenges of adulthood. This exploratory study was conducted to examine the impact that this chronic illness has on the developmental processes of adults. Methods triangulation was used to examine the content of unprompted, written goals and the results of surveys of life satisfaction and mood states of 138 persons with heart failure. Younger adults had higher anger, depression, and anxiety scores than older or middle-aged adults and had lower scores of life satisfaction. This may reflect the emotional reaction to the realization that their lives may be shortened by this chronic illness. Analysis of their goals reflected the developmental challenges described by Erikson. Despite severe physical limitations, these individuals demonstrated growth and achievement of developmental tasks by transcending usual time lines.

Estradiol regulation of the human retinoic acid receptor alpha gene in human breast carcinoma cells is mediated via an imperfect half-palindromic estrogen response element and Sp1 motifs.

Estrogen receptor (ER)-positive human breast carcinoma (HBC) cell lines express significantly higher levels of retinoic acid receptor alpha (RAR alpha) (isoform 1) mRNA than ER-negative HBCs. Estradiol enhances RAR alpha mRNA expression in different ER-positive HBCs by 2-3-fold, which in turn results in increased sensitivity of ER-positive HBCs to the growth inhibitory effects of retinoic acid. To investigate the regulatory mechanisms of estradiol-mediated enhancement of RAR alpha mRNA expression, the functional promoter for the human RAR alpha isoform 1 was cloned and used to assess estradiol-mediated promoter-dependent enhancement of firefly luciferase reporter gene activity in transiently transfected ER-positive (MCF-7 and T47D) and ER-negative (MDA-MB-231) HBCs. Deletional promoter constructs were obtained to further delineate the promoter region responsible for estradiol-mediated enhancement of promoter activity. Here, we present evidence that approximately 130 bp of the promoter fragment preceding the transcriptional start site are responsible for estradiol-mediated enhancement of hRAR alpha gene expression. The estradiol-mediated enhancement is dependent on ER binding. Further deletional analysis showed that a promoter sequence of 42 base pairs, located approximately 100 bases upstream of the transcriptional start site, contains elements for estradiol-mediated enhancement. Specific deletion of either the Sp1 motif or mutations in the imperfect half-palindromic estrogen response element motif of this fragment abolish its estradiol responsiveness in transient transfections.

Retinoid-resistant estrogen receptor-negative human breast carcinoma cells transfected with retinoic acid receptor-alpha acquire sensitivity to growth inhibition by retinoids.

Retinoids mediate their actions via RARs (retinoic acid receptors) and RXRs (retinoid X receptors). Each class of these nuclear retinoid receptors is further subdivided into three species, namely alpha, beta, and gamma. Recent studies demonstrate that estrogen receptor (ER)-positive human breast carcinoma (HBC) cell lines and tumor samples exhibit significantly higher levels of RAR alpha than their ER-negative counterparts. ER-positive HBC cell lines are sensitive to, and ER-negative cell lines are resistant to, growth inhibitory effects of retinoic acid (RA). We previously demonstrated that the expression of functional ERs in an established ER-negative cell line resulted in higher levels of RAR alpha and sensitivity to growth inhibition by RA. To further investigate the major role of RAR alpha in retinoid-mediated inhibition of growth, we transfected RAR alpha cDNA in two RA-resistant ER-negative HBC cell lines. Analyses of different clonal populations of RAR alpha transfectants from each cell line revealed growth inhibition by retinoids. Utilizing RAR- and RXR-class selective retinoids, we further demonstrated that only the RAR alpha-selective retinoids mediated the growth inhibition in these cells, while the RXR-selective retinoids were biologically inert. We thus provide evidence that the molecular mechanisms of retinoid inhibition of HBC proliferation predominantly involve RAR alpha.

Cell-to-cell communication: a differential response to TGF-beta in normal and transformed (BEAS-2B) human bronchial epithelial cells.

The effects of transforming growth factor beta (TGF-beta) on cell-to-cell communication were investigated in the log phase of growth in normal BE and in adenovirus-12 SV40 hybrid virus transformed BE cells (strain BEAS-2B). Gap junctions in these cells were identified immunocytochemically. Exposure of BE cells to exogenous TGF-beta (0.04-4.0 pM) in serum-free keratinocyte growth medium (KGM) for 1 or 24 h reduced the rate of fluorescent dye transfer (i.e. cell-to-cell communication) by 30-50% in BE cells. Inversely, in BEAS-2B cells, TGF-beta after 1 h induced a 2- to 10-fold increase in the rate of dye transfer. After 24 h of TGF-beta, communication among BEAS-2B cells was not significantly different from controls (no exogenous TGF-beta). The protein kinase C (PKC) inhibitor H-7 induced a dose-dependent enhancement in communication, which was even higher in the presence of TGF-beta (4 pM X 24 h). The calmodulin antagonist W-7 enhanced communication in BEAS-2B cells independently of the presence of TGF-beta. In keratinocyte basal medium (KBM) supplemented with EGF (5 ng/ml) or with TGF-beta (4.0 pM) dye transfer was reduced or enhanced respectively. The combination of EGF and TGF-beta in KBM antagonized the stimulatory effect of the latter on communication in BEAS-2B cells. In BE cells, continuous exposure (4 days) to TGF-beta in KGM induced a dose-dependent inhibition of proliferation and an increased expression of a keratinized, epidermoid phenotype. This correlated with a reduction in the expression of a mucous secretory phenotype. Increased exposure to TGF-beta (0.04-4.0 pM) decreased the labeling index in BEAS-2B cells, but the cells retained a growth advantage over normal BE cells, and did not express a keratinized epidermoid morphology. With respect to dye transfer as an index of cell-to-cell communication, we conclude (i) that an inhibition or enhancement of communication is involved in the response of bronchial epithelial cells to mitogens (e.g. epidermal growth factor) or growth inhibitors (e.g. TGF-beta), (ii) that PKC and Ca(2+)-calmodulin-dependent processes regulate dye transfer, and (iii) the effects of TGF-beta are mediated by PKC.

Chemotherapy for breast cancer decreases plasma protein C and protein S.

An increased incidence of thromboembolic events has been described in women receiving chemotherapy for breast cancer. The etiology of this enhanced thrombotic state has not been defined. We performed serial coagulation studies in 15 women during 1 monthly cycle of cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for breast cancer; seven adjuvant and eight metastatic. Plasma protein C levels were measured by anticoagulant, amidolytic, and antigenic techniques. Antigen levels of both total and free plasma protein S were quantitated by immunoelectrophoresis. Plasma levels of protein C, an important vitamin K-dependent inhibitor of blood coagulation and a profibrinolytic agent, and protein S, a cofactor for protein C, decreased 1 and 2 weeks after initiation of chemotherapy compared with pretreatment values. Plasma levels of factor VII and fibrinogen also decreased. The changes in protein C and protein S may contribute to the enhanced thrombotic tendency described in this setting. Possible mechanisms for the decreases in plasma protein C, protein S, factor VII, and fibrinogen are discussed.