Glucocorticoids and androgens up-regulate the Zn-α2-glycoprotein messenger RNA in human breast cancer cells

Summary We have studied the hormonal regulation of the gene encoding Zn-₂-glycoprotein (Zn-₂-gp), a human protein with a high degree of amino acid sequence similarity to class I histocompatibility antigens that is produced by a specific subset of breast carcinomas. Northern blot analysis revealed that dexamethasone and 5-dihydrotestosterone strongly induced the accumulation of Zn-₂-gp mRNA in T-47D human breast cancer cells. Furthermore, the effect of these two hormones was shown to be additive, since the combination of both hormones produced a stimulation of Zn-₂-gp mRNA of at least 3-fold over that produced by either hormone alone. By contrast, the addition of 5-dihydrotestosterone, 17-estradiol, or progesterone failed to induce the expression of Zn-₂-gp. The stimulatory effect of glucocorticoids and androgens on Zn-₂-gp expression was produced in a time and dose dependent manner, without significantly affecting the cell proliferation rate. A time-course study demonstrated that the induction of Zn-₂-gp mRNA by androgens and glucocorticoids reached a level of 4 or 3.2-fold over the untreated control after seven days of incubation in the presence of a 10^–7 M concentration of 5-dihydrotestosterone or dexamethasone, respectively. A dose-response study showed that as little as 10^–11 M of 5-dihydrotestosterone or dexamethasone produced an accumulation of Zn-₂-gp mRNA of 2.4 or 2.1-fold over the control, respectively. On the basis of these results, we propose that Zn-₂-gp may be useful as a biochemical marker of breast carcinomas with a specific pattern of hormone responsiveness in whose development glucocorticoids and/or androgens may play a significant role.     

A sudden increase in plasma epinephrine levels transiently enhances platelet deposition on severely damaged arterial wall--studies in a porcine model

Epidemiologic evidence has shown that sympathoadrenal activation plays a triggering role in the onset of acute coronary syndromes. However, its mechanism is not yet clearly understood. The aim of this study was to assess the effect of a sudden increase in epinephrine on platelet deposition on severely damaged vessel wall at shear rate conditions modelling stenotic vessels in the porcine model. The selected epinephrine concentrations (0.5 micromol/l-1 mmol/l) alone or in combination with collagen or ADP did not affect platelet aggregation in vitro either in whole blood or in PRP, although porcine platelets express alpha2-adrenergic receptors as assessed by PCR. In vitro and ex vivo perfusion experiments were performed using the Badimon chamber at high shear rate conditions (1690 s(-1)). In vitro, epinephrine (130 nmol/l) increased platelet deposition on severely damaged vessel wall (exposing tunica media; approximately 1.6-fold, p <0.05) or immobilized collagen (2.2-fold, p <0.01). Ex vivo perfusion experiments were performed from animals that received intravenous epinephrine infusion for one hour at a low (0.3 microg/kg/min; approximately 17 nmol/l in plasma, at 20 min of the infusion) and a high dose (1.0 microg/kg/min; approximately 106 nmol/l in plasma, at 20 min of the infusion). Only the low dose temporarily increased platelet deposition on severely damaged vessel wall during the first 30 min of infusion [2.4-fold (p <0.05) and 4.2-fold (p <0.01) at 10 and 30 min of the infusion respectively] declining afterwards. Thus, in flow conditions typical of atherosclerotic arteries, a sudden physiological release of epinephrine can temporarily enhance platelet deposition on severely damaged vessel wall while an extensive exposure leads to refractoriness.     

Genetic markers in primary open-angle glaucoma

Purpose: To investigate possible associations between genetic markers and Primary Open-Angle Glaucoma (POAG). Methods: A number of genetic markers were typed in 84 unrelated patients with POAG and compared with a random sample of healthy individuals. The markers were Transferrin, Group Specific Component, G1m (1), G1m (2) and G3m (5) Allotypes, Adenylate Kinase, Adenosin Deaminase, Glyoxalase I and Acid Phosphatase and PCR-based markers HLA-DQA1 and D1S80. Results: No significant differences were found except the strong association between the group of POAG patients and Acid Phosphatase ACP^*C allele (² = 32.86; p < 0.0001). Conclusions: Since Acid Phosphatase gene is localized to chromosome 2p23, this result could be a first comprehensive step in the localization of POAG genes.     

Effect of an opiate antagonist (naloxone) on the gastric acid secretory response to sham feeding,pentagastrin, and histamine in man

We studied the effect of the opiate antagonist naloxone on the human gastric acid secretory response to three secretory stimulants: sham feeding, pentagastrin, and histamine. Intravenous naloxone (40 g/kg/hr) significantly inhibited the acid secretory response to sham feeding without affecting the serum gastrin response to sham feeding. Naloxone also significantly reduced pentagastrin- and histamine-stimulated acid secretion. These studies indicate that naloxone reduces acid secretion in response to all stimulants of acid secretion yet tested in humans.This study was supported by grants AM-16816 and AM-17328, from the National Institute of Arthritis, Metabolism and Digestive Diseases.Presented in part at the Plenary Session of the American Gastroenterological Association, Salt Lake City, Utah, May 19, 1980.     

Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.     

Hispanic health status in Orange County, Florida.

PURPOSE: To assess the health status of the Hispanic population of Orange County, Florida. METHODS: The methodology utilized secondary data for 66 ethnically identified indicators in a comparative framework applied for a 5-year period (1997-2001). FINDINGS: Orange County Hispanics are younger with lower per capita income than their Florida peers, less likely to be White, and much more likely to be of Puerto Rican origin. Relative to the Hispanic populations in the selected peer counties and statewide, Orange County Hispanics have higher age-adjusted death rates for a majority of disease categories and conditions, such as breast, lung, and prostate cancers; chronic liver disease and cirrhosis; diabetes mellitus; pneumonia and influenza; stroke; acquired immunodeficiency syndrome; motor vehicle accidents; and infant, neonatal, and child mortality. Orange County Hispanics did better in comparison to Orange non-Hispanics, with lower age-adjusted death rates for major causes of death such as heart disease, cancer, and stroke. However, for many indicators, the 5-year trends for Orange County Hispanics are moving in an unfavorable direction in contrast to the trends for non-Hispanics, which are either stable or improving. CONCLUSION: Comparative assessments of Hispanic populations using secondary data enable the development of a comprehensive health status profile. However, this approach is currently constrained by the limited number of ethnically identified indicators and, especially for Hispanics, problems in the accuracy and consistency of the assignment to racial categories and subsequent reporting.     

An interactive and contextual model of community-university collaborations for research and action.

Community-university partnerships for research and action are at the heart of many fields in the social sciences including public health, urban planning, education, and community psychology. These partnerships involve individuals from different backgrounds and disciplines working together to address social issues of importance to the community. This article proposes an interactive and contextual model for developing and sustaining community-university partnerships. The phases in the model include gaining entry into the community, developing and sustaining a mutual collaboration (developing trust and mutual respect, establishing adequate communication, respecting human diversity, establishing a culture of learning, respecting the culture of the setting and the community, and developing an action agenda), and recognizing the benefits and outcomes of partnership work. The model also includes the potential challenges that might threaten the partnership, such as resource inequality and time commitment.     

Reliability and agreement of adipose tissue fat fraction measurements with water–fat MRI in patients with manifest cardiovascular disease

The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical‐shift water–fat multi‐echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficient_agreement, ICC_agreement) was 0.97 for test–retest, 0.95 for intra‐observer and 0.56 for inter‐observer measurements, which increased to 0.88 when ICC_consistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) ?1.7 to 2.6) for test–retest, ?0.5% (LoA ?2.9 to 2.0) for intra‐observer and 5.6% (LoA 0.4 to 10.8) for inter‐observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6–84.0) and 89.7% (IQR 87.2–91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water–fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue. Copyright © 2015 John Wiley & Sons, Ltd.