Biomedical subjects

E A Stone

Publications and source records attributed to E A Stone.

At least 55 records · Page 3Linked to original sources

PubMed1991

Noradrenergic activation of immediate early genes in rat cerebral cortex.

Previous studies have shown that stimulation of adrenergic receptors in the brain increases the expression of the immediate early gene (IEG), c-fos, in vivo (Mol. Brain Res., 6(1989) 39-45). The present study was undertaken to determine whether this also holds for other IEGs which have been shown to be activated in brain cell culture by adrenergic agonists. Both yohimbine injection and stressful stimulation, two treatments causing brain norepinephrine (NE) release, were found to cause a parallel, transient activation of at least 5 IEGs (c-fos, nur77, tis-7, zif-268 and tis-21) in the rat cortex. Genes that are not immediate early (beta-actin, NGF and HSP70) were found not to be affected in the interval used (6 h). The responses were mediated predominantly by beta-adrenoceptors with some contribution from alpha 1 receptors. The parallel activation of multiple genes by noradrenergic receptors may enable the coding of different biochemical responses to the activation of different receptors.

Animals↗

PubMed1990

Glial localization of adenylate-cyclase-coupled beta-adrenoceptors in rat forebrain slices.

Fluorocitrate (FC), a selective inhibitor of glial cell respiration, was used to estimate the extent to which glial cells contain adenylate cyclase-coupled beta-adrenoceptors in rat brain slices. The drug blocked 75-95% of the elevation of cyclic AMP caused by the beta-agonist, isoproterenol, in the 4 forebrain regions sampled (frontal and parietal cortex, caudate nucleus, olfactory tubercle). Intracellular recording of neurons in the treated slices confirmed that they were unaffected by FC. Treatment with the neurotoxin, kainic acid, eliminated all electrophysiological activity but did not affect the cAMP response. The results indicate that glial cells contain the preponderance of adenylate-cyclase-coupled beta-adrenoceptors in slices of the rat forebrain and may constitute an important target of the central noradrenergic system in vivo.

Adenosine Triphosphate↗

PubMed1990

Surgically induced tumor seeding in eight dogs and two cats.

Surgically induced tumor seeding was diagnosed in 8 dogs and 2 cats. All animals had histologic confirmation of neoplasia in an unusual location or pattern, and a history of surgical manipulation of a similar histologic-type tumor at the site of seeding. Highly malignant carcinomas (8/10 animals) were the most common tumor type. Seeding occurred secondary to a variety of surgical procedures and in the face of various adjuvant therapies. Seeded tumors were recognized from 2 to 30 weeks after the causal procedure (median, 6 weeks). Survival times after the causal procedure ranged from 15 to 131 weeks (median, 45 weeks) and 8 of 10 animals died or were euthanatized because of seeded tumors.

Animals↗

PubMed1990

In vivo measurement of extracellular cyclic AMP in the brain: use in studies of beta-adrenoceptor function in nonanesthetized rats.

Microdialysis measurement of extracellular cyclic AMP (cAMP) in the cerebral cortex of conscious rats was evaluated as a method for assessing central beta-adrenoceptor function in vivo. Extracellular levels of the nucleotide were found to average 3 pmol/ml under baseline conditions. Local infusion of the beta-agonists norepinephrine (NE) and isoproterenol produced rapid (3 min) and marked (three- to sevenfold) dose-dependent increases in extracellular cAMP, which were potentiated by the phosphodiesterase inhibitor rolipram, and blocked by the beta-antagonist timolol. Responses to both catecholamines underwent rapid desensitization (6-9 min) and recovered within several hours. Time-course studies revealed that the baseline cAMP level underwent a gradual increase and then a decrease over the course of a single 8-h run, and peaked at 24 h postimplantation. Responses to NE were stable for the first 24 h after implantation, then increased at 48 and 120 h. The causes of the latter changes may include reactions to novelty, local inflammatory responses, and/or reactions of adjacent glial cells to implantation. Overall, the results indicate that the microdialysis-cAMP method can be extended to nonanesthetized animals and may be a useful tool for studying neurotransmission at central adenylate cyclase-coupled membrane receptors during various behavioral states.

Anesthesia↗

PubMed1989

Catecholamine-induced desensitization of brain beta adrenoceptors in vivo and reversal by corticosterone.

The function of beta adrenoceptors in the brain was studied with a new technique involving the microdialysis collection of extracellular cyclic AMP (cAMP). Prolonged infusion of isoproterenol (2 hr) was found to induce a marked desensitization of the beta receptor-cAMP response. Administration of corticosterone (10 mg/kg) 3 hrs prior to the infusion markedly attenuated the desensitization. The results indicate that the catecholamine-induced densensitization of brain beta adrenoceptors can be studied in vivo and that corticosterone is capable of reversing this effect in the brain as has been reported previously for peripheral tissues.

Animals↗

PubMed1988

Use of microdialysis to measure brain noradrenergic receptor function in vivo.

The present studies were undertaken to explore the use of intracerebral microdialysis to measure brain adrenergic receptor activity in vivo using the efflux of cyclic adenosine monophosphate (cAMP) in the extracellular fluid as an index of receptor function. An initial study with brain slices showed that extracellular levels of cAMP were highly correlated with intracellular levels after noradrenergic receptor activation. Detectable levels of extracellular cAMP were obtained from microdialysis probes implanted in the frontal cortex. Stable levels (3.5 +/- 2.7 pmol/ml) were obtained between 1.5 and 7 h after implantation. Perfusion of probes with NE (10(-5) to 10(-3) M) led to dose-dependent increases in cAMP efflux. The response to NE was blocked by infusion of the beta-antagonist, timolol, indicating that it reflected beta-receptor activation. Similar responses were obtained at 2 and 24 h after implantation indicating that the responses were not affected by acute traumatic effects of implantation. The findings show that the microdialysis technique can be successfully applied to the in vivo study of central adrenoceptor function. This suggests that the in vivo measurement of second messengers by microdialysis will provide a valuable new neurochemical and neuropharmacological technique.

Animals↗

PubMed1988

Renal dysfunction in dogs with pyometra.

Renal function and pathologic changes in 27 dogs with pyometra were studied. Evaluation included CBC; serum biochemical evaluation; urinalysis; urine and uterine bacteriologic culture; uterine morphologic features; and light, electron, and immunofluorescent microscopic evaluation of renal tissues. Measurements of 24-hour creatinine clearance, protein excretion, Na excretion, and urine volume were made in 12 dogs without azotemia. Of 27 dogs, 26% were azotemic and 89% had a urine sp gr less than 1.035. Glomerular filtration rate was reduced in 75% of 12 dogs without azotemia. None of these 12 dogs was proteinuric. Examination of renal biopsy specimens revealed a high prevalence of mild tubulointerstitial nephritis, but few specific glomerular lesions. Minimal immunofluorescence was detected within the mesangium in 18% of the dogs. Immunofluorescence was not associated with the interstitium or tubules. Urinary tract infection was detected in 22% of the dogs. Escherichia coli and Klebsiella were recovered from the uterus in 59 and 15% of the dogs, respectively. Low urine specific gravity values were obtained from dogs without azotemia and from dogs with uterine cultures considered negative for E coli and other gram-negative bacteria. The reduction in glomerular filtration rate was a functional abnormality not correlated with structural damage in the glomerulus.

Animals↗

PubMed1988

Architecture and structure of canine veins with special reference to confluences.

The occurrence of cell-infiltrated intimal lesions at the confluence of many small tributaries with canine jugular and femoral veins suggested that these areas (confluences) might 1) differ structurally from the rest of the receiving vein and 2) serve as initiation sites for thrombi. To explore these possibilities, the number of tributaries was determined by careful blunt dissection, and the architecture of confluences was studied by light and scanning and transmission electron microscopy. In addition to confluences formed by a named tributary (omobrachial), canine jugular veins averaged 11 confluences formed with small (0.2 to 2.5 mm diameter) unnamed tributaries that had not been previously described. Femoral veins averaged eight confluences of which four were formed with small unnamed tributaries. Double-leafed valves were found at 90% of jugular and 76% of femoral vein confluences. Previously such valves were described only at the confluence of superficial with deep leg veins. Corrosion casts of iliac, saphenous, azygous, costocervical, and maxillary veins as well as cranial and caudal vena cava demonstrated a similar pattern of tributaries and valves. The three structures (receiving vein, tributary, valves) that formed the confluence differed, necessitating considerable modification as they approached the area of fusion. Jugular and femoral vein walls contained 5 to 10 layers of smooth muscle, abundant collagen, and a small amount of elastin. Tributary walls contained 0 to 2 discontinuous smooth muscle cell layers, limited collagen, and no elastin. As receiving veins approached a confluence, the thickness decreased by 15 to 77% except at valve attachment sites, which were thickened. A cluster of smooth muscle cells formed the junction of valve leaflets with vein. Endothelium was continuous over the luminal surface of all three structures. Calculations showed that these small-valved tributaries make only a small contribution to venous return. On the other hand, there is considerable information to support the concept that local attenuation of the vein wall would lead to localized vessel dilation, resulting in rupture of the endothelium and basement membrane.

Animals↗

PubMed1988

Novel effect of chronic corticosterone treatment on escape behavior in rats.

Chronic administration of corticosterone in rats (4-35 mg/kg/day) produces a marked dose-dependent increase in the frequency of escape behavior observed when animals are held by the tail on a flat surface. The effect is fully developed after 3 days treatment. It is not the result of an increase in spontaneous motor activity since the hormone tends to reduce the latter behavior. Adrenalectomy decreases the escape behavior and tends to do so to a greater degree in rats subjected to chronic stress (restraint) than in nonstressed controls. The results suggest that endogenous corticosterone serves to maintain the above escape behavior during chronic stress.

Administration, Oral↗

PubMed1988

Ureterocolonic anastomosis in clinically normal dogs.

Ureterocolonic anastomosis was evaluated in 13 clinically normal dogs. Urinary continence was maintained after surgery, and the procedure was completed without technique errors in all but 2 dogs. Three dogs died within 5 weeks (2 of undetermined causes and 1 of aspiration pneumonia and neurologic disease), and 1 dog was euthanatized 4 months after surgery because of neurologic signs. Two healthy dogs were euthanatized 3 months after surgery for light microscopic evaluation of their kidneys. Five dogs were euthanatized 6 months after surgery for light microscopic evaluation of their kidneys. Gastrointestinal and neurologic disturbances developed in 4 dogs at various postoperative intervals. Plasma ammonia concentration measured in 2 dogs with neurologic signs was increased. Plasma ammonia concentration measured in 5 dogs without neurologic signs was within normal limits. All 5 dogs, in which metabolic acidosis was diagnosed, had high normal or above normal serum chloride concentration. Serum urea nitrogen values were increased after surgery because of colonic absorption of urea. Serum creatinine concentration was increased in 1 dog 6 months after surgery. Individual kidney glomerular filtration rate was reduced in 38% (3/8) of the kidneys from 4 other dogs at 6 months after surgery. Of 5 dogs euthanatized at 3 to 4 months after surgery, 4 had bilateral pyelitis, and 1 had unilateral pyelonephritis. Six months after surgery, pyelonephritis was diagnosed in 40% (4/10) of the kidneys from 5 dogs. The ureterocolonic anastomosis procedure is a salvage procedure that should allow complete cystectomy. However, variable degrees of metabolic acidosis, hyperammonemia, and neurologic disease may result.

Anastomosis, Surgical↗

PubMed1987

Regulation of alpha and beta components of noradrenergic cyclic AMP response in cortical slices.

The cyclic AMP response to catecholamines in the rat cerebral cortex is mediated by both beta- and alpha-adrenoceptors. The beta-receptors cause a direct activation of adenylate cyclase whereas the alpha alpha-receptors play a modulatory role and act by potentiating the response to beta stimulation. The present study investigated whether the functions of these two types of cyclic AMP-linked receptors are regulated differently by various physiological factors known to affect adrenoceptor function. It was found that treatments that affect central noradrenergic neuronal function including repeated administration of desmethylimipramine or lesion of central noradrenergic pathways produced selective changes in the cAMP response to beta-receptor stimulation whereas treatments that affect adrenocortical function including ACTH of corticosterone administration and hypophysectomy or adrenalectomy produced selective changes in the potentiation response to alpha-receptor stimulation. The change in the alpha potentiation effect caused by corticosterone was found to be abolished in the presence of prazosin indicating that the hormone affects alpha 1-adrenoceptor function. The results support the hypothesis that the beta response in the cortex is under the control of the noradrenergic system while the alpha potentiation response is under the control of the adrenocortical system.

Adrenalectomy↗

PubMed1987

Reduction in 2-deoxy-D-glucose analgesia following acute, but not chronic antidepressant treatment.

Acute, but not chronic, antidepressant treatment potentiates the analgesic responses following cold-water swims. The present study evaluated the effects of acute (10 mg/kg) and chronic (10 mg/kg, twice daily over 7 days) pretreatment with desipramine (DMI) upon the analgesic response following 2-deoxy-D-glucose (2DG) in rats as measured by the jump test. Acute, but not chronic, DMI pretreatment significantly reduced 2DG analgesia. These effects are discussed in terms of the heterogeneity of pain-inhibitory responses.

Analgesics↗

PubMed1987

Central cyclic-AMP-linked noradrenergic receptors: new findings on properties as related to the actions of stress.

Central noradrenergic receptors that control cyclic AMP formation in the brain may be involved in the process of adaptation to stress and in the clinical actions of antidepressant drugs. The present paper reviews recent findings on the properties and susceptibility to stress of these receptors. Two types of adrenergic receptors are known to mediate the central cAMP response, beta and alpha receptors. It has been found that chronic stress causes a selective desensitization of the alpha receptors (alpha-1 subtype) producing a partial reduction of the overall cAMP response to catecholamines. This desensitization occurs in the cerebral cortex, hypothalamus and possibly other areas of the forebrain. The physiological factor responsible for the effect appears to be an elevated corticosterone secretion. The behavioral function of the stress-induced desensitization may be to reduce behavioral inhibition and facilitate the recovery of behavioral function during adaptation to stress.

Brain↗

PubMed1987

Use of ultrasound for noninvasive study of blood vessel responsiveness.

To provide a noninvasive means for studying individual macroscopic blood vessels, an ultrasound scanner was modified to provide a recording of blood vessel diameter. The instrument has A- and B-modes of signal display. The B-mode is used to position the probe and the A-mode to measure vessel diameter. The A-mode has two electronic gates for tracking the echo from each of two structures, i.e., near and far wall of vessel. The front gate was modified to pick up the falling rather than rising edge of a peak generated by the vessel wall. An analog signal proportional to the distance between gates was derived for recording with a strip-chart recorder. Probe holders were constructed to optimize positioning and holding of probe. Stability was excellent (reading varied 0.05 mm over 1 h). Axial resolution was between 0.3 and 0.73 mm. Discrepancy of measurements of plastic tubing made by ocular and ultrasound varied from 1.1 to 4.6%. Discrepancy with lightly fixed vessels was 2.7-8.2%. Ex vivo measurements on vessels with viable smooth muscle were more variable, perhaps because of actual change during measurements. Changes in vessel diameter induced by change in hydrostatic pressure and exposure to histamine were recorded.

Animals↗

PubMed1986

Alpha-adrenergic modulation of cyclic AMP formation in rat CNS: highest level in olfactory bulb.

The cyclic adenosine monophosphate response to catecholamines in the rat brain is mediated by beta-adrenergic receptors which activate adenylate cyclase and by alpha-adrenergic receptors which potentiate the response to beta-stimulation. We have found that the alpha-potentiation effect in the olfactory bulb is 2-3X greater than in other forebrain areas. This correlates with the extremely high density of alpha-receptors in this brain region and makes it a useful model for the study of alpha-receptor function.

Animals↗

PubMed1986

Effect of repeated restraint stress, desmethylimipramine or adrenocorticotropin on the alpha and beta adrenergic components of the cyclic AMP response to norepinephrine in rat brain slices.

The cyclic AMP response to catecholamines in rat cortical slices is mediated by a beta adrenergic receptor which is coupled to adenylate cyclase and an alpha adrenergic receptor which potentiates the response to beta receptor stimulation. The present studies examined the effects of repeated restraint stress, adrenocorticotropin or desmethylimipramine administration on the beta and alpha adrenergic components of this response. Restraint was found to produce a small nonsignificant decrease of the beta receptor response accompanied by a significant reduction of the alpha receptor-induced potentiation of the beta response. Desmethylimipramine was found to lower the cyclic AMP response to beta receptor stimulation but not to alter the alpha-induced potentiation of the beta response. Adrenocorticotropin, like restraint stress, was found to reduce only the alpha-induced potentiation of the beta response. Experiments with adenosine and histamine showed that restraint stress lowered the alpha-induced potentiation of cyclic AMP responses to these neurohormones also. It is concluded that restraint stress acts primarily to reduce the response to stimulation of central alpha adrenergic receptors whereas desmethylimipramine acts primarily to reduce the response to stimulation of beta adrenergic receptors. Adrenocorticotropin has the same effect as restraint stress suggesting that pituitary adrenal hormones mediate the stress effect.

Adenosine↗

PubMed1985

Pylorectomy and gastroduodenostomy in the dog: technique and clinical results in 28 cases.

Pylorectomy and end-to-end gastroduodenostomy are surgical procedures that allow excision of abnormal pyloric tissue and provide improved gastric outflow. These techniques were used for the treatment of benign, malignant, and ulcerative conditions that were judged to be not adequately treatable with pyloromyotomies or pyloroplasties. End-to-end gastroduodenostomy was not much more difficult than a standard intestinal anastomosis; however, a thorough knowledge of the pyloric area anatomy was required to avoid serious surgical errors. In addition, gentle tissue manipulation and precise suture placement reduced the chance of iatrogenic pancreatitis, biliary obstruction, tissue ischemia, and/or suture line leakage. The results of surgery depended on the underlying disease process. Dogs with benign lesions such as chronic hypertrophic pyloric gastropathy responded favorably to treatment. Dogs with malignant disease and perforated ulcers had low long-term survival rate. Pyloric adenocarcinoma was not adequately treated with this method alone.

Animals↗

PubMed1985

Chronic hypertrophic pyloric gastropathy as a cause of pyloric obstruction in the dog.

Six small-breed, middle-age dogs with a history of chronic intermittent vomiting had benign pyloric lesions causing gastric outlet obstruction. Marked similarities were found in clinical signs, pathologic changes, and treatment results. The condition was classified as a syndrome and was named chronic hypertrophic pyloric gastropathy. The appearance of the obstructive lesions at surgery were various forms of mucosal hypertrophy. Microscopically, the syndrome was characterized by mucosal foveolar and glandular hyperplasia, cystic glandular dilatation, superficial mucosal ulcerations, and various cellular infiltrates. The affected dogs were successfully treated by surgical correction of the gastric outlet obstruction.

Animals↗