Effect of estrogen supplementation on exercise thermoregulation in premenopausal women

This study examined the effects of 3 days of estrogen supplementation (ES) on thermoregulation during exercise in premenopausal (20-39 yr) adult women during the follicular phase of the menstrual cycle. Subjects (11 control, 10 experimental) performed upright cycle ergometer exercise at 60% of maximal O2 consumption in a neutral environment (25 degreesC, 30% relative humidity) for 20 min. Subjects were given placebo (P) or beta-estradiol (2 mg/tablet, 3 tablets/day for 3 days). All experiments were conducted between 6:30 and 9:00 AM after ingestion of the last tablet. Heart rate, forearm blood flow (FBF), mean skin temperature, esophageal temperature (Tes), and forearm sweat rate were measured. Blood analysis for estrogen and progesterone reflected the follicular phase of the menstrual cycle. Maximal O2 consumption (37.1 +/- 6.2 in P vs. 38.4 +/- 6.3 ml. kg-1. min-1 in ES) and body weight-to-surface area ratio (35.58 +/- 2.85 in P vs. 37.3 +/- 2.7 in ES) were similar between groups. Synthesis of 70-kDa heat shock protein was not induced by 3 days of ES. Neither the threshold for sweating (36.97 +/- 0.15 in P vs. 36.90 +/- 0.22 degreesC in ES), the threshold for an increase in FBF (37.09 +/- 0. 22 in P vs. 37.17 +/- 0.26 degreesC in ES), the slope of sweat rate-Tes relationship (0.42 +/- 0.16 in P vs. 0.41 +/- 0.17 in ES), nor the FBF-Tes relationship (10.04 +/- 4.4 in P vs. 9.61 +/- 3.46 in ES) was affected (P > 0.05) by 3 days of ES. We conclude that 3 days of ES by young adult women in the follicular phase of their menstrual cycle have no effect on heat transfer to the skin, heat dissipation by evaporative cooling, or leukocyte synthesis of 70-kDa heat shock protein.     

The origin of the alpha-domain intermediate in the folding of hen lysozyme

Stopped-flow fluorescence and circular dichroism spectroscopy have been used in conjunction with quenched-flow hydrogen exchange labelling, monitored by electrospray ionization mass spectrometry, to compare the refolding kinetics of hen egg-white lysozyme at 20 degrees C and 50 degrees C. At 50 degrees C there is clear evidence for distinct fast and slow refolding populations, as observed at 20 degrees C, although folding occurs significantly more rapidly. The folding process is, however, substantially more cooperative at the higher temperature. In particular, the transient intermediate on the major refolding pathway at 20 degrees C, having persistent native-like structure in the alpha-helical domain of the protein, is not detected by hydrogen exchange labelling at 50 degrees C. In addition, the characteristic maximum in negative ellipticity and the minimum in fluorescence intensity observed in far UV CD and intrinsic fluorescence experiments at 20 degrees C, respectively, are not seen at 50 degrees C. Addition of 2 M NaCl to the refolding buffer at 50 degrees C, however, regenerates both the hydrogen exchange and optical properties associated with the alpha-domain intermediate but has no significant effect on the overall refolding kinetics. Together with previous findings, these results indicate that non-native interactions within the alpha-domain intermediate are directly responsible for the unusual optical properties observed during refolding, and that this intermediate accumulates as a consequence of its intrinsic stability in a folding process where the formation of stable structure in the beta-domain constitutes the rate-limiting step for the majority of molecules.     

Novel D-ring analogues of podophyllotoxin as potent anti-cancer agents

Insulin is one of the hormonal regulators of leptin synthesis and participates in adipose tissue maintenance. The present study was undertaken to clarify the association of endogenous insulin secretion and mode of therapy with body fat and serum leptin levels in diabetic subjects. We measured the fasting serum C-peptide level, as an estimate of endogenous insulin secretion, and the serum leptin level in 176 Japanese diabetic subjects (79 men and 97 women; age, 55.9+/-14.3 years; body mass index [BMI], 23.8+/-4.1 kg/m2 [mean+/-SD]). Thirty-one subjects were treated with diet therapy alone, 66 with sulfonylurea (SU), and 79 with insulin (including 29 with type I diabetes mellitus). Body fat was analyzed by the impedance method. Serum leptin levels significantly correlated with the BMI and body fat and were higher in women, mainly because of their greater body fat. Serum C-peptide concentrations positively correlated with body fat and serum leptin in subjects treated with diet and SU. In insulin-treated type II diabetic subjects, both serum C-peptide and the daily insulin dose were weakly associated with body fat and serum leptin. In those subjects, despite a lower percent body fat and body fat mass, serum leptin concentrations (10.3+/-8.4 ng/mL) were comparable to the levels in subjects treated with diet (8.8+/-8.5 ng/mL). When compared within the same BMI and body fat groups (BMI 20 to 25 and > 25 kg/m2) including the control subjects matched for age and sex, serum leptin levels were higher in insulin-treated type II diabetic subjects versus the control subjects and diabetic patients treated with diet or SU. Stepwise regression analysis for all of the diabetic subjects showed that both the serum C-peptide level and exogenous insulin administration, as well as the BMI, gender, and age, were determinants of the serum leptin level. In conclusion, endogenous insulin secretion is closely associated with body fat and serum leptin in diabetic subjects treated with diet therapy and SU. In Japanese insulin-treated type II diabetic subjects, both endogenous and exogenous insulin are associated with body fat and serum leptin, which is maintained at levels comparable to or somewhat higher than the levels in control subjects and diabetic patients treated without insulin.     

Carvedilol: the new role of beta blockers in congestive heart failure

The prognosis remains poor for patients with congestive heart failure (CHF), despite reduced mortality rates resulting from the addition of angiotensin converting enzyme inhibitors to traditional treatment regimens. Because much of the myocardial damage that occurs in patients with CHF may be related to sympathetic activation, interest in the use of beta blockers has grown. Recent studies have shown the benefits of beta blocker therapy in many patients with heart failure. Carvedilol, the first beta blocker labeled in the United States specifically for the treatment of heart failure, has been shown to improve left ventricular ejection fraction and may reduce mortality.     

Sex role psychodynamics in psychotherapy supervision

Supervision of the female psychotherapy neophyte is discussed in relation to sex role-exacerbated ambivalence toward the transition from classroom passive-dependency to self-reliance as a professional clinician. Supervisors are alerted to hostile-dependent strategies, such as seductive flattery, that serve immediate ego-protective needs but ultimately block the attainment of fuller professional functioning.     

On the mechanism of hypocholesterolemic action of amphotericin B in rat

The transient hypocholesterolemia phenomenon observed in rats, injected i.v. with amphotericin B (1.5 mg/kg/day) for three weeks, was investigated by in vitro [14C] acetate incorporation into the liver cholesterol. The incorporation of acetate in liver slices of treated animals increased more than two-fold (p less than 0.02) when compared with controls.When amphotericin B was added in vitro to liver slices of control rats, the incorporation of acetate into cholesterol decreased to about 65% of that observed with the corresponding controls (p less than 0.01). The results are consistent with the hypothesis that initially amphotericin B causes inhibition of de novo cholesterol synthesis resulting in hypocholesterolemia which disappears on continued treatment possibly due to compensatory increased rate of cholesterol biosynthesis.     

Effects of perceiving and imagining scenes on memory for pictures

Boundary extension is the tendency to remember having seen a greater expanse of a scene than was shown. Four experiments tested whether a picture must depict a partial view of a scene for the distortion to occur. The premise was that partial views activate a perceptual schema, a representation of the expected scene structure outside the view. Participants were 473 undergraduates. Experiments 1 and 2 tested recognition memory and recall of 16 outline-objects presented in outline-scenes versus presentation on blank backgrounds. Experiments 3 and 4 compared memory for outline-objects when scene context was or was not imagined. Boundary errors consistent with the perceptual schema hypothesis only occurred for partial views (perceived or imagined). Results suggest that scene perception and imagination activate the same schematic representation.     

A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer

In order to test the effect of a psychological intervention on survival from cancer, 66 women with metastatic breast cancer, all receiving standard medical care, were randomly assigned into two groups; one group (n = 30) attended the psychological intervention, consisting of 35 weekly, 2 h sessions of supportive plus cognitive behavioral therapy; the control group (n = 36) received only a home study cognitive behavioral package. No significant difference was found in survival post-randomization between the groups as assessed by a log rank test 5 years after the commencement of the study. As expected, several prognostic factors were significant predictors of survival: metastatic site, hormonal receptor status, and chemotherapy prior to randomization. While many personal and demographic variables did not influence survival, there was a significant effect of self-reported exercise (possibly due to better health). A small subgroup of intervention subjects who attended outside support groups also survived significantly longer than those who did not. The strengths and limitations of the present study are discussed, and the results contrasted with those of a well known study by Spiegel et al. (Spiegel, D., Bloom, J.R., Kraemer, H.C. and Gottheil, E. (1989) Lancet ii, 888-891). We propose that a different experimental design (correlative) may be needed to show any effect of self-help behaviors and psychological attributes in a small minority of patients.