Research and clinical practice.
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Biomedical subjects
Publications and source records attributed to B Moon.
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The uridine diphosphoglucose pyrophosphorylase (UDPGP1) gene of Dictyostelium discoideum is an excellent marker to study the pathways that control the expression of genes during development. We have previously shown that the UDPGP1 gene is regulated by exogenous cAMP acting on cell-surface cAMP receptors. Various steps in the signal transduction pathway between receptor stimulation and the induction of the gene can now be studied. Induction does not require the synthesis of intracellular cAMP, but does require new protein synthesis. By deletion and transformation with altered genes, two cis-acting sequences that are required for UDPGP1 expression have been identified. A GC-rich palindromic sequence located between -410 and -374 is essential for induction of the gene by extracellular cAMP, but not for its basal expression. A sequence element located between -374 and -337 is required for any basal expression of this gene. When the polarity of the palindromic sequence was reversed such that it resembled the H2K enhancer element, the gene could still be induced by exogenous cAMP. Two DNA binding activities were detected in gel mobility shift assays using a fragment containing both of the regulatory sequence elements of UDPGP1 gene. Transformation with a vector that resulted in the synthesis of anti-sense UDPGP1 RNA led to almost total elimination of the enzyme antigen and no detectable enzyme activity. However, these transformants developed normally, indicating that either UDPGP is not required for development or residual synthesis of UDPGP may be sufficient for normal development.
The sutureless intraluminal prosthesis was used in 22 patients with acute dissection of the ascending aorta (type A) between May, 1982, and September, 1985. The patients ranged from 26 to 77 years old (mean, 58 years). Diagnosis was established by aortogram in 18 patients and by two-dimensional echocardiogram in 4 patients. Additional procedures included resuspension of the aortic valve in 7 patients, single coronary artery bypass in 1 patient, and cesarean delivery of a term pregnancy in 1 patient. Nineteen patients survived operation and were discharged from the hospital (86% early survival). Three patients died, 2 of hemorrhage and myocardial failure in the operating room, and 1 of sepsis following a prolonged hospitalization. Early postoperative complications included one instance of renal failure, one perioperative myocardial infarction, and one cerebrovascular accident (CVA). There were no reoperations for bleeding. Follow-up was obtained on 17 patients (90%) and ranged from 10 to 50 months (mean, 30 months). Thirteen of the survivors are well, 11 have returned to work, 2 have had a CVA, and 1 has a descending thoracic aneurysm. We conclude that the intraluminal graft is a good option for repair of acute type A dissections because it reestablishes central aortic flow, obliterates the false channel entry site, minimizes operative blood loss, and permits expeditious repair with minimal trauma to friable tissues.
The purpose of this study was to examine the effects of prior nonspecific immune stimulation (BCG), cross-reactive immunization (E coli J5 0111 whole cells [J5 WC], and core glycolipid [J5 CGL]), and type-specific immunization (Serratia marcescens core glycolipid [SM CGL]) on the cardiopulmonary variables and white blood cell counts of awake, monitored sheep following IV Serratia marcescens endotoxin. Comparison of cardiac output, pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, alveolar-arterial oxygen gradients, and total white blood cells lead us to conclude that type-specific immunization (SM CGL) most effectively ameliorates the changes of gram-negative endotoxemia contrasted to nonimmunization. Core glycolipid cross-reactive (J5 CGL) immunization was somewhat more effective than whole-cell cross-reactive (J5 WC) immunization in this regard. Nonspecific immune stimulation (BCG) was able only to significantly decrease the changes in pulmonary vascular resistance compared to nonimmunization.
Naloxone (0.80 mg/kg) and morphine (7.5 mg/kg) were given to rats or guinea pigs with increasing doses of amphetamine (0.5-6.0 mg/kg) to determine their respective effects on amphetamine-induced stereotypy. In contrast to the inhibiting and potentiating effect of these agents on apomorphine-induced stereotyped behavior, naloxone enhanced and morphine markedly attenuated amphetamine-induced stereotypy. Since other investigators have reported that drugs inhibiting release of dopamine block amphetamine-induced stereotypy and enhance apomorphine-induced stereotypy, whilst compounds stimulating the release of dopamine potentiate amphetamine-induced stereotypy and inhibit apomorphine-elicited stereotyped behavior, it is likely that naloxone stimulates and morphine inhibits the release of DA following their acute administration.
A determination was made of the roles played by the selective uptake inhibition versus release of dopamine (DA) or norepinephrine (NE) ex vivo in either the striatum or cerebral cortex in mediating d-amphetamine induced locomotor activity (AILA). Desmethylimipramine (DMI) and/or d-amphetamine variously effected the uptake of DA and NE in both regions in terms of the absolute amount of uptake inhibition elicited by each drug separately or by the two drugs administered concomitantly. However, none of the drug treatments produced a selective inhibition of DA or NE uptake in either the striatum or cerebral cortex. On the other hand, a selective inhibition of central DA release by gamma-hydroxybutyrate markedly inhibited AILA. These results suggest that amphetamine induced locomotor activity is not likely mediated by a preferential effect on DA or NE uptake. It is far more probable that AILA is induced by a stimulation of central DA release.