Autologous Unpurged Bone Marrow Transplantation for Acute Non Lymphoblastic Leukemia in First Remission

Forty consecutive adult patients under the age of 50 with acute non-lymphoblastic leukemia (ANLL) in first complete remission, underwent autologous bone marrow transplantation (ABMT) between March 1984 and April 1990. The conditioning regimen employed included cyclophosphamide and total body irradiation, followed by the administration of unpurged ABMT. The median time from diagnosis to transplant was 7 months (3-15 months), and the median time from complete remission to ABMT was 4 months (range 3-9 months). Twenty-two (51%) patients remain in complete remission 6-81 months (median 24 months) after ABMT.

The causes of death were, recurrent leukemia (11 patients), parenchymal toxicities such as acute respiratory distress syndrome and veno-occlusive disease (3 patients), hemorrhage (2 patients) and infection (2 patients). Eleven patients relapsed after 3-12 months (median 5 months). This study has produced survival data comparable to those of other institutions employing TBI for either allo or autotransplants.     

Dopamine D-1 but not D-2 receptor stimulation of the dorsal striatum potentiates apomorphine-induced jaw movements in rats

The effects of bilateral injections of selective D-1 and D-2 agonists and antagonists into the dorsal striata on apomorphine-induced jaw movements were studied in ketamine-anaesthetized rats after C1 spinal transection. A phototransducer attached to the lower mandible automatically detected jaw movements. YM-09151-2 (0.2 and 0.5 micrograms) and cis(Z)-flupentixol (0.5 and 1 microgram) injected into the dorsal striatum increased the frequency of jaw movements after apomorphine (0.2 mg/kg i.v.). The effects were prevented by administration of SCH23390 (1 microgram) with YM-09151-2 (0.5 microgram) or cis(Z)-flupentixol (1 microgram). Injection of SCH23390 (1 microgram) alone into the dorsal striatum failed to alter the apomorphine (0.5 mg/kg i.v.)-induced jaw movements. Local application of the selective D-1 agonists, SKF38393 (5 micrograms) and SKF75670 (10 micrograms), into the dorsal striatum potentiated the apomorphine (0.2 mg/kg i.v.)-induced jaw movements, while a D-2 agonist, quinpirole (10 micrograms), injected into the same site attenuated these movements. These data are suggestive of an oppositional D-1: D-2 receptor interaction in the dorsal striatum.     

Natural history of experimental pulmonary atelectasis in dogs with closed chest

In order to establish an animal model of pulmonary vasoconstriction we followed the time course of intrapulmonary shunt (Qs/Qt) in a canine model of lobar atelectasis with closed chest. Ten mongrel dogs were studied. Bronchial occlusion of the right lower lobe (RLL) was performed by inflating the balloon of a Foley catheter placed through a rigid bronchoscopy. Analysis of variance was used for statistical analysis. (15 minutes) After occlusion Qs/Qt reached its maximum increasing from 8.2 +/- 3.6 to 29.7 +/- 11.7% (p less than 0.05) and PaO2 decreased from 357 +/- 49 to 100 +/- 43 mm Hg (p less than 0.05). Afterwards, there was a progressive decline of Qs/QT accompanied by an also progressive increase in PaO2. At the end of the experiment (3 hrs post atelectasis) Qs/Qt was 11.2 +/- 4.9 and PaO2 251 +/- 124 mm Hg (p less than 0.05). Pulmonary vascular resistance increased post atelectasis from 439 +/- 168 to 598 +/- 256 d.s.cm-5 (p less than 0.05). Complete atelectasis of the RLL was confirmed postmortem. As the changes in Qs/Qt and PaO2 did not parallel the change in cardiac output we conclude that the mechanism of decrease in Qs/Qt was hypoxic vasoconstriction.     

Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute G_i/o-coupled receptor activation inhibits the activity of several AC isozymes, including Ca²⁺/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute μ-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of {ie195-2} subunits ({ie195-3} scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that {ie195-4} is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.     

Mild atopic dermatitis lacks systemic inflammation and shows reduced nonlesional skin abnormalities

1. Download : Download high-res image (227KB)
2. Download : Download full-size image

     

Competing functions encoded in the allergy-associated F(c)epsilonRIbeta gene

Allergic reactions are triggered via crosslinking of the high-affinity receptor for immunoglobulin E, F(c)epsilonRI. In humans, F(c)epsilonRI is expressed as a tetramer (alphabetagamma(2)) and a trimer (alphagamma(2)). The beta subunit is an amplifier of F(c)epsilonRI surface expression and signaling. Here, we show that as a consequence of alternative splicing, the F(c)epsilonRIbeta gene encodes two proteins with opposing and competing functions. One isoform is the full-length classical beta, the other a novel truncated form, beta(T). In contrast to beta, beta(T) prevents F(c)epsilonRI surface expression by inhibiting alpha chain maturation. Moreover, beta(T) competes with beta to control F(c)epsilonRI surface expression in vitro. We propose that the relative abundance of the products of the beta gene may control the level of F(c)epsilonRI surface expression and thereby influence susceptibility to allergic diseases.     

The effect of caffeine ingestion on physical performance after prolonged exercise

Summary The purpose of this study was to determine the effect of caffeine ingestion on physical performance after prolonged endurance exercise. Twenty three trained male volunteers participated in a 40-km march and were divided into two groups, matched for caffeine clearance rate and aerobic capacity. The experimental group ingested, prior to the march, a caffeinated drink at a dose of 5 mg·kg⁻¹ body mass and at the 3rd and 5th h of marching an additional drink at a dose of 2.5 mg·kg⁻¹ body mass. The control group ingested a drink of equal volume at the same times. Upon termination of the march each subject performed a cycle ergometer test at an intensity of 90% maximal oxygen consumption. Time to exhaustion and rate of perceived exertion (RPE) were recorded. Blood samples were drawn predrink, at the 3rd and 5th h of marching and immediately after the cycle ergometer test, and were analysed for caffeine, free fatty acids (FFA), lactate and glucose levels. Plasma FFA levels increased during the march (p<0.05), with no significant difference between groups. Lactate levels increased in the experimental group (p<0.05), with no significant change in the control group. Glucose levels did not change significantly in either group. After the cycle ergometer test, lactate levels were significantly higher in the experimental, as compared to the control group (3.77±0.33 vs 2.52±0.35 mmol·l⁻¹, respectively). There was no significant difference between treatments in the time to exhaustion on the cycle ergometer, but RPE was different (p<0.05). Under the conditions of this study, the results do not indicate caffeine ingestion as an ergogenic aid which will postpone exhaustion following prolonged endurance exercise. This work was presented, in part, at the Canadian Association of Sports Sciences Annual Meeting, October 1987, Lake Louise, Alberta, Canada