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Biomedical subjects

E A Stone

Publications and source records attributed to E A Stone.

At least 37 records · Page 2Linked to original sources

Placement of a permanent cystostomy catheter to relieve urine outflow obstruction in dogs with transitional cell carcinoma.

Permanent cystostomy catheters were placed in 7 dogs to relieve urine outflow obstruction from presumed transitional cell carcinoma of the bladder trigone and urethra. The catheters were easily managed at home by the owners. Complications were minimal. The most frequent complication was urinary tract infection. Two owners complained of difficulty in draining the bladder 1 week before euthanasia of their dogs. The primary reason for euthanasia of all dogs was progression of the tumor. Survival times of these dogs were similar to those previously reported for dogs with transitional cell carcinoma involving the bladder and urethra, irrespective of treatment. Placement of a permanent cystostomy catheter should be considered in dogs with transitional cell carcinoma associated with urine outflow obstruction when, owing to the dog's condition or the owner's preference, radical surgery or other treatment is not an option.

Animals↗

Massive activation of c-fos in forebrain after mechanical stimulation of the locus coeruleus.

Brief implantation of a 33-ga cannula in the locus coeruleus (LC) of the rat caused widespread and intense ipsilateral activation of c-fos throughout the forebrain. Areas showing heavy staining included the cingulate, piriform, parietal, frontal cortex, and the olfactory tubercle. Prior lesion of the LC with 6-hydroxydopamine (6-OHDA) abolished the response. It is concluded that the mechanical stimulation and/or trauma involved in the implantation of a cannula in the LC is sufficient to cause widespread activation of noradrenergic neurotransmission throughout the forebrain. The use of this procedure for drug delivery should therefore be reevaluated.

Animals↗

Biopsy: principles, technical considerations, and pitfalls.

Biopsy is an essential part of the diagnostic workup for cancer patients. Percutaneous, endoscopic, catheter, incisional, and excisional biopsies have different indications, accuracy, and efficacy. Careful attention to biopsy technique will minimize complications and increase the accuracy and efficacy of the biopsy procedure. Intraoperative biopsy and microscopy can be used in selected instances to modify the surgical plan.

Animals↗

Beta adrenoceptor blockade mimics effects of stress on motor activity in mice.

Reduced central noradrenergic function has been implicated as a factor in reduced behavioral activity after stress. The present studies examined the role of reduced beta adrenergic neurotransmission in mediating this effect. This was done by testing the ability of beta receptor antagonists to mimic the behavioral actions of stress. Mice were subjected to stress or given various beta antagonists and tested for swimming behavior, locomotor activity, or grooming behavior. As previously reported, stress reduced swimming and locomotor activity and increased grooming. Both the nonselective antagonist, l-propranolol, and the beta-1 selective antagonist, betaxolol, produced the same effects as stress on all three measures. A beta-2 selective antagonist, ICI 118,551, was effective only on swimming, whereas a membrane stabilizing agent, d-propranolol, was effective only on grooming behavior. The peripherally active beta-1 antagonist, atenolol, was not effective on any measure. The nonspecific dopaminergic receptor blocker, fluphenazine, reduced locomotion but tended also to reduce grooming. The results indicate that blockade of beta-1 receptors in the CNS selectively mimics the action of stress on gross motor activity in mice and, along with previous data, suggest that stress leads to a relative deficiency in central beta-1 noradrenergic neurotransmission in these animals.

Adrenergic beta-Antagonists↗

Locus coeruleus lesions potentiate neurotoxic effects of MPTP in dopaminergic neurons of the substantia nigra.

The observation that Parkinson's disease (PD) is associated with locus coeruleus (LC) noradrenergic neuronal degeneration suggests that the LC noradrenergic system may be involved in the pathogenesis and natural progression of the destruction of the substantia nigra (SN) dopaminergic neurons in Parkinson's disease. The relationship of these two systems was examined by injection of subtoxic doses of MPTP into unilateral LC 6-hydroxydopamine (6-OHDA) lesioned mice. A significant loss of dopaminergic cells was only found in the SN on the side of the LC lesions. These results suggest that the LC may have protective effects on SN dopaminergic neurons.

Animals↗

Effect of yohimbine on nerve growth factor mRNA and protein levels in rat hippocampus.

Activation of noradrenergic receptors has been shown to increase expression of nerve growth factor (NGF) gene in brain cells in vitro. The present studies were undertaken to determine if this stimulation was effective in vivo as well. Rats were administered the norepinephrine-releasing drug, yohimbine (YOH), and had their hippocampi assayed for NGF mRNA and protein at various times after the injection. It was found that yohimbine caused a 3-fold increase of NGF mRNA levels at 24 h. Protein levels, however, were unaltered at this time. Thus norepinephrine release in vivo appears to be sufficient for increasing mRNA level but not for translation to protein.

Animals↗

Immunohistochemical localization of mu-opioid receptors in rat brain using antibodies generated against a peptide sequence present in a purified mu-opioid binding protein.

Light-microscope visualization in rat brain of a pattern of distribution of immunoreactivity, which included immunolabeled perikarya and beaded processes, was achieved using an immunoaffinity purified polyclonal antibody, Ab165, which recognizes the amino acid sequence, IRNLRQDRSKYY, found in the mu-opioid binding protein purified in our laboratory. Immunohistochemical staining with Ab165 was carried out by the avidin-biotin procedure. Antibody, preabsorbed with antigen, served as control. Extensive immunoreactivity was seen in the hippocampal formation, the amygdaloid complex, the striatal complex, cortical regions, select areas of the thalamus and hypothalamus and in laminae I and II of the dorsal horn in spinal cord. The distribution of immunoreactivity in the rat brain of antibody 165, which recognizes a purified mu-opioid binding protein, is concordant with the distribution of mu-opioid binding sites as determined by other laboratories in autoradiographic, electrophysiological and immunocytochemical studies. These findings have enabled us to distinguish areas possessing large fields of mu-opioid receptor containing cell bodies from areas possessing dense networks of immunolabeled neuronal processes or mixtures of both.

Amino Acid Sequence↗

Characterization of the non-linear loading curve of rat skin.

A phenomenological model was developed to characterize the non-linear portion of stress-strain curves for skin tissue removed from laboratory rats and tangent modulus calculations were used to characterize the linear portion of the curves. Modified coefficient of determination calculations obtained from non-linear regression analysis showed that the model was able to fit the actual data above the 90% level. The model coefficients and tangent modulus values were used to statistical comparisons. Combination treatments of radiation, hyperthermia and surgical incision were used to analyze changes in the loading response of rat skin. Least significant difference statistical analysis (P < 0.10) of the model coefficients showed that radiation treatment affected skin stiffness only in tissue when surgical wounding was applied and that radiation-hyperthermia treatment affected skin stiffness only in tissue when surgical wounding was not applied. Hyperthermia applied with no radiation treatment did not affect skin stiffness. Surgical wounding resulted in decreasing skin stiffness.

Animals↗

Effect of locus coeruleus lesion on c-fos expression in the cerebral cortex caused by yohimbine injection or stress.

The injection of the alpha-2 adrenoceptor antagonist, yohimbine, has been shown to increase c-fos immunoreactivity in the rat cerebral cortex. To determine the extent to which this response is mediated by the central noradrenergic system, the present studies examined it in rats previously given unilateral 6-OHDA lesions of the locus coeruleus. The lesions were found to produce a significant attenuation of the response. A similar effect on the c-fos immunoreactive response to restraint stress was found. It is concluded that the noradrenergic system plays a necessary role in the above c-fos responses in the cortex to yohimbine and to stress. The c-fos protein therefore appears to be involved in the effects of noradrenergic neurotransmission in the CNS.

Animals↗

Stress-induced increase of extracellular levels of cyclic AMP in rat cortex.

Previous studies have suggested that stress may increase levels of cyclic AMP (cAMP) in the brain but these findings have been controversial due to the use of stressful procedures to inactivate brain enzymes. The present experiment therefore used a non-stressful technique, microdialysis, to assay extracellular levels of cAMP in the rat cortex after stress. Experiments were conducted 2 days after implantation of probes in the frontal cortex. Significant increases were found after the mild stressors of restraint or intraperitoneal injection of saline suggesting that increased tissue levels of cAMP had occurred. These responses were potentiated by local infusion of the phosphodiesterase (PDE) inhibitor, rolipram. It is concluded that one or more adenylate cyclase-coupled receptors in the cortex is activated by mild stress and that this activation can be detected in vivo by microdialysis.

Adenylyl Cyclases↗

Immunohistochemical studies of noradrenergic-induced expression of c-fos in the rat CNS.

Previous studies have shown that stimulation of adrenergic receptors in the rat brain causes increased levels of mRNA of the immediate early gene, c-fos. The present studies were undertaken to determine if this stimulation also induces increased levels of c-fos immunoreactivity in the central nervous system (CNS). Rats were treated with the alpha-2 adrenoceptor blockers, yohimbine or atipamezole, or with restraint stress to activate central noradrenergic activity and were perfused 2 h later for immunohistochemical analysis of the cerebral cortex. Yohimbine, atipamezole and restraint stress each was found to cause increases in c-fos-like immunoreactivity (c-fos-li). Western blot analysis revealed increased c-fos protein in the cortex after yohimbine treatment. The c-fos-li response to yohimbine was blocked by prior administration of the beta receptor antagonist, dl-propranolol, and to a lesser degree by the alpha-1 antagonist, prazosin. It is concluded that adrenergic receptor stimulation in the cortex causes increased production of c-fos or fos related antigens and that this (these) immediate early gene product(s) may play a role in noradrenergic function in the CNS.

Adrenergic alpha-Antagonists↗

Noradrenergic-induced expression of c-fos in rat cortex: neuronal localization.

beta Adrenoceptors in the rat forebrain have been shown to exist predominantly on astrocytes. Studies were undertaken to determine whether the cellular localization of c-fos expression caused by the activation of brain beta receptors would have a similar cellular localization. Double label light and electron microscopic immunohistochemical experiments with a glial (glial fibrillary acidic protein, GFAP) and neuronal marker (neurofilament protein, NFP) were undertaken in rats treated with the adrenergic drug, yohimbine. These studies revealed a predominantly neuronal localization of Fos protein in the cerebral cortex. The latter results indicate that neurons are the postsynaptic noradrenergic target cells in which this immediate early gene is expressed in response to the stimulation of beta adrenoceptors. The possible relation of these findings to the glial localization of these receptors is discussed.

Animals↗

Effects of freezing on mechanical properties of rat skin.

Two test specimens of skin were cut from the lateral aspect of each hind limb of 9 rats. Specimens were contiguous, thereby providing matched pairs. One specimen was immediately placed in liquid nitrogen for 5 minutes, then stored at -70 C and tested within 3 to 4 weeks. Within 5 minutes of harvest, the second specimen was used for immediate material testing. Basic engineering material tests were used to measure strength, loading response, and elastic and viscous properties. Each matched pair of tissues was used for the same procedure. Quasistatic uniaxial tensile tests were used to apply deformations to the test specimens, and resulting loads were recorded. Stress and strain were calculated from the recorded data, providing information on yield strength, ultimate strength, fracture strength, and loading response. Each matched pair of specimens represented 1 repetition; 6 repetitions were made of each observation. Statistical analysis indicated that tissue freezing significantly (P less than 0.05) increased fracture strength, but did not affect strength, ultimate strength, or loading response. Dynamic vibration response tests were used to find mechanical mobility of the specimens, thereby providing information on elastic and viscous behaviors, which were quantified by calculation of spring and damping coefficients, respectively. As before, 6 repetitions were used. Statistical analysis indicated that tissue freezing did not affect these coefficients.

Animals↗

c-Fos response to administration of catecholamines into brain by microdialysis.

The present studies investigated the use of microdialysis for the infusion of catecholamines into the brain in studies of immediate early gene (IEG) activation. c-Fos like immunoreactivity was examined histochemically in cortical tissue surrounding a dialysis probe implanted in the medial prefrontal cortex. No c-fos reactivity was observed at 48 h post implantation in control animals not probe-infused or infused 2 h earlier with Ringer's buffer. Marked reactivity was found in animals infused with a solution of norepinephrine (NE). The latter was blocked by coinfusion of the beta adrenoceptor antagonist, timolol. It is concluded that direct infusion of NE by dialysis can induce c-fos expression in cells of the cerebral cortex and that this effect is primarily via beta-adrenoceptors. Microdialysis therefore represents a useful technique in studies of IEG responses to brain catecholamines.

Animals↗

Sinus mucocele secondary to craniofacial trauma in a dog.

A sinsus mucocele formed in the frontal sinus of a dog secondary to obstruction of the nasofrontal opening. The dog was successfully treated by surgical enlargement of the nasofrontal opening, curettage of the sinus epithelium, and placement of a fat graft and drain in the sinus. Although mucocele formation is uncommon in animals, it should be considered as a differential diagnosis for masses of the sinonasal area. Characteristic radiographic and cytologic findings should alert the clinician to this diagnosis, and along with aggressive treatment, should shorten the diagnostic and treatment delay experienced by the dog in this report.

Animals↗

Further evidence for a glial localization of rat cortical beta-adrenoceptors: studies of in vivo cyclic AMP responses to catecholamines.

The present experiments were designed to clarify the cellular localization of postsynaptic beta-receptors in the rat cortex by studying the cellular source and pharmacological characteristics of in vivo cAMP responses to catecholamines. The method used to study in vivo cAMP responses in the brain involved microdialysis both to deliver catecholamines to cerebral tissue and to sample cAMP released in response to local beta-receptor activation. It was found that selective blockade of the metabolism of glial cells by fluorocitrate infusion produced a virtually complete (90%) inhibition of the cortical cAMP response to norepinephrine (NE). Selective damage of neurons by kainic acid infusion had little effect on the response. Pharmacological experiments showed that the response was selectively antagonized by a beta 1-receptor blocker which also selectively antagonized the cAMP response to NE in brain slices known to be localized in glial cells. These results support the hypothesis that beta-adrenoceptors of the rat cortex are predominantly localized on glial cells and therefore strongly suggest that these cells are an important target of the locus coeruleus noradrenergic system.

Analysis of Variance↗