Interaction of [D-Pen2,D-Pen5]enkephalin and [D-Ala2,Glu4]deltorphin with delta-opioid receptor subtypes in vivo

A total of 78 patients with superficial bladder carcinoma were prospectively randomized to two groups following complete transurethral resection (TUR). Each received 12 intravesical instillations of 10(7) units interferon A or 120 mg BCG Connaught for 1 year starting 6 weeks post-TUR. After a mean observation period of 24 (13-31) months in the BCG and 25 (6-32) months in the IFN group 5/32 (15.6%) recurrences in the BCG versus 21/35 (60%) in the IFN group were observed (P = 0.0003). In the IFN group 18.4% of the patients had dysuria and 2.6% fever; in the BCG group 35% had fever, 60% cystitis, 1 patient granulomatous epididimoorchitis and 1 patient pneumonitis with granulomatous prostatitis. With our instillation regimen interferon A had few side effects but also no prophylactic effect, whereas BCG had tolerable-seldom severe--side effects and was very effective in preventing recurrences. Perhaps IFN should be given earlier after TUR and in a higher dosage.     

Judgments of learning and the allocation of study time

OBJECTIVE: The aim was to determine whether cocaine has a direct effect on the myocardium which is independent of coronary vasospasm. METHODS: Cocaine was introduced into the perfusate of the isolated rabbit ventricular septal preparation in the concentration range 10(-5) to 10(-3)M while holding coronary flow of oxygenated Krebs solution constant at 3.0 ml.min-1 by a perfusion pump. The septa were obtained from white male New Zealand rabbits and were paced at 48 beats.min-1. Mechanical and enzymatic measurements were performed. RESULTS: Developed tension (T), maximum contraction velocity (+dT/dt), and maximum relaxation velocity (-dT/dt) were all depressed to approximately the same degree at each different cocaine concentration and averaged 4, 48, and 95% at 10(-5), 10(-4), and 10(-3)M cocaine respectively, with an ED50 = 9 x 10(-5)M. Relaxation time (tR/T) was prolonged, but the ED50 was greater (by 1.5 times) than for the other mechanical parameters. Simultaneously, an increase in excitation threshold dysrhythmia developed which resulted in 17, 50, and 90 beats missed per 100 stimulations at 10(-5), 10(-4), and 10(-3)M cocaine respectively. Resting tension (RT) was not altered. Coronary flow rate was not reduced in presence of cocaine because of the constant delivery pump. T, +dT/dt, -dT/dt and modulation of the excitation threshold completely recovered after washout of cocaine. CONCLUSIONS: Cocaine has acute direct, though reversible, depressant effects on the myocardium, including depression of function and modulation of excitation threshold, which are independent of its effect on coronary flow.     

Apoptosis as a possible cause of gradual development of complete heart block and fatal arrhythmias associated with absence of the AV node, sinus node, and internodal pathways

BACKGROUND: Gradually progressive development of complete heart block in young people often is associated with cardiac arrhythmia and sudden death, but the pathogenesis remains unexplained. METHODS AND RESULTS: A young woman with complete heart block died suddenly. Her mother had serological but no clinical evidence of antiphospholipid syndrome. Five brothers of another family had arrhythmia and heart block. Three died suddenly; the other two have automatic defibrillators and are alive. The hearts from the young woman and two of the three brothers who died were available for our histological examination of their cardiac conduction systems. In two of the three hearts, the AV node was absent; in the third heart, only fragments of the AV node remained. In all three hearts, the sinus node was nearly destroyed by a noninflammatory degeneration with no abnormal fibrosis or infiltrate. In each heart, the interatrial and internodal pathways were similarly involved, and in the young woman, there were no myocardial cells in which these pathways normally exist. CONCLUSIONS: In these three subjects with progressive development of complete heart block and various arrhythmias, all of whom died suddenly, the histological abnormalities of their cardiac conduction systems are best interpreted as resulting from apoptosis. Programmed cell death is a logical explanation for the pathogenesis of this puzzling clinical picture.     

Depressive symptoms in patients with systemic lupus erythematosus: association with central nervous system lupus and Sj?gren's syndrome

OBJECTIVE: To determine if patients with systemic lupus erythematosus (SLE) with depressive symptoms differ in regard to organ involvement and serological activity from other patients with SLE. METHODS: Disease manifestations were compared between 71 patients with SLE with a history of depressive symptoms and 278 patients without a history of depressive symptoms by univariate analysis and multiple logistic regression. RESULTS: Both univariate and logistic regression analysis revealed an association of depressive symptoms with neuropsychiatric lupus and secondary Sj?gren's syndrome (SS). Patients with neuropsychiatric lupus had an adjusted odds ratio of 3.43 (95% CI 2.55, 4.63; p = 0.00005), and patients with secondary SS had an adjusted odds ratio of 2.97 (95% CI 2.08, 4.25; p = 0.0006) for depressive symptoms. No other organ involvement or serological abnormality was associated with depressed mood. CONCLUSION: These discrete associations of depressive symptoms with neuropsychiatric lupus and secondary SS suggest that depression does not occur purely as a response to social stresses, and may be a manifestation of autoimmune disease in some patients.     

The 1.5-A resolution crystal structure of bacterial luciferase in low salt conditions

Bacterial luciferase is a flavin monooxygenase that catalyzes the oxidation of a long-chain aldehyde and releases energy in the form of visible light. A new crystal form of luciferase cloned from Vibrio harveyi has been grown under low-salt concentrations, which diffract x-rays beyond 1.5-A resolution. The x-ray structure of bacterial luciferase has been refined to a conventional R-factor of 18.2% for all recorded synchrotron data between 30.0 and 1.50-A resolution. Bacterial luciferase is an alpha-beta heterodimer, and the individual subunits fold into a single domain (beta/alpha)8 barrel. The high resolution structure reveals a non-prolyl cis peptide bond that forms between Ala74 and Ala75 in the alpha subunit near the putative active site. This cis peptide bond may have functional significance for creating a cavity at the active site. Bacterial luciferase employs reduced flavin as a substrate rather than a cofactor. The structure presented was determined in the absence of substrates. A comparison of the structural similarities between luciferase and a nonfluorescent flavoprotein, which is expressed in the lux operon of one genus of bioluminescent bacteria, suggests that the two proteins originated from a common ancestor. However, the flavin binding sites of the nonfluorescent protein are likely not representative of the flavin binding site on luciferase. The structure presented here will furnish a detailed molecular model for all bacterial luciferases.     

Effects of suramin on neuroendocrine and behavioural responses to conditioned fear stimuli

Conditioned fear stimuli suppress motor activity. The fear stimuli suppress vasopressin and facilitate oxytocin and prolactin release. These fear responses are impaired by selective destruction of noradrenergic neurones. Adenosine 5'-triphosphate is co-released from noradrenergic nerve terminals with noradrenaline. Thus the possibility arises that the behavioural and neuroendocrine responses may be mediated by purinergic rather than noradrenergic synapses. We examined whether suramin, an inhibitor of P2 and NMDA receptors, blocks conditioned fear responses. Suramin injected i.c.v. 30 min before testing stimuli impaired conditioned fear responses. The role of purinergic P2 receptors in expression of the behavioural and neuroendocrine responses to conditioned fear stimuli is discussed.     

Bulimic adolescents benefit from massage therapy

Twenty-four female adolescent bulimic inpatients were randomly assigned to a massage therapy or a standard treatment (control) group. Results indicated that the massaged patients showed immediate reductions (both self-report and behavior observation) in anxiety and depression. In addition, by the last day of the therapy, they had lower depression scores, lower cortisol (stress) levels, higher dopamine levels, and showed improvement on several other psychological and behavioral measures. These findings suggest that massage therapy is effective as an adjunct treatment for bulimia.     

Analysis of pulsatile secretion of thyrotropin and growth hormone in the hypothyroid rat

To characterize the role of TRH in the generation of TSH pulsatility as well as the effect of hypothyroidism on episodic GH secretion, blood was constantly withdrawn (30-60 microliters/min) from rats treated with 0.02% methimazole in the drinking water for 8-10 days. This treatment significantly reduced circulating levels of both T3 and T4 and elevated plasma TSH; however, since thyroid hormone titers were still detectable (T3, 39.6 +/- 5.3 vs. 89.8 +/- 5.3 ng/dl in euthyroid animals), methimazole-treated rats were referred to as being mildly hypothyroid. TSH was found to be secreted in secretory bursts, consisting of one to several peaks in these rats. Pulsar analysis of TSH secretory profiles revealed a mean pulse frequency of 2.8 pulses/h, a mean pulse amplitude of 10 ng/pulse, and a mean pulse duration of 0.2 h. Euthyroid rats exhibited similar fluctuations of circulating TSH levels; however, due to the variability of the TSH RIA in the range of euthyroid TSH titers, no significant pulsatility was detected by Pulsar. Mean plasma TSH levels in eu- and hypothyroid rats were 2.3 +/- 0.3 and 14.6 +/- 1.8 ng/ml, respectively. To confirm that the TRH antiserum (TRH-AS) used in the present study for passive immunization had sufficient binding capacity to absorb endogenous TRH release, euthyroid rats were pretreated with either normal rabbit serum or TRH-AS, followed by the injection of clonidine (100 micrograms/kg BW, iv). This alpha 2-adrenergic agonist caused a significant (P < 0.01) 12.7-fold rise in plasma TSH levels in normal rabbit serum-treated animals, which was completely abolished by TRH-AS pretreatment, indicating that clonidine stimulates TSH secretion via activation of hypothalamic TRH release. When TRH-AS was slowly infused into hypothyroid rats that were sampled frequently for the detection of TSH pulsatility, it caused a significant (60.3%; P < 0.01) decrease in mean TSH levels, with TSH titers approaching euthyroid concentrations 1 h after the infusion of TRH-AS. The antiserum treatment also caused the disappearance of statistically significant (Pulsar) TSH secretory pulses. Mild hypothyroidism shifted the GH secretory profiles from a low frequency, high amplitude in euthyroid animals to a high frequency, low amplitude pattern in hypothyroid rats. Mean GH levels in hypothyroid rats were 76% lower than those in euthyroid controls. These findings show that TSH is secreted in a pulsatile fashion in the hypothyroid rat and that TRH is predominantly responsible for the generation of TSH pulsatility.(ABSTRACT TRUNCATED AT 400 WORDS)