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K M Murphy

Publications and source records attributed to K M Murphy.

At least 127 records · Page 7Linked to original sources
PubMed1991

A computational model for the overall pattern of ocular dominance.

In layer IV of the primary visual cortex, in both the macaque monkey and the cat, geniculocortical terminals representing the two eyes are segregated into alternating zones known as ocular dominance bands. Viewed tangentially, in the monkey these bands take the form of a series of branching parallel stripes that run roughly perpendicular to the border of striate cortex. In the cat, the overall ocular dominance pattern consists of irregularly branching, beaded bands that exhibit no predominant orientation. If the striking differences in the appearance of these two patterns reflect important differences in the basic rules governing cortical ocular dominance, then this poses a problem for attempts to formulate general principles of visual cortical organization. However, it has been suggested that the differences in the appearance of the ocular dominance patterns in these two species could result simply from known differences in the boundary conditions of their geniculocortical pathways. This article describes the formulation and testing of a single computational model that accurately predicts the quite dissimilar ocular dominance patterns in cats and monkeys. This model also generalizes to predict the different ocular dominance patterns observed in young and old three-eyed frogs, supporting the notion that the overall pattern of ocular dominance is governed by a common set of rules. The significance of these results is discussed in terms of previous models, which have focused largely on local processes underlying the development of ocular dominance segregation. Although the present model is not a developmental one, it does shed some light on potential mechanisms for establishing retinotopy in striate cortex and on possible developmental relationships between the geniculostriate pathway and intrinsic modularity of the striate cortex.

Animals↗
PubMed1990

Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo.

In order to examine the mechanisms by which clonal deletion of autoreactive T cells occurs, a peptide antigen was used to induce deletion of antigen-reactive thymocytes in vivo. Mice transgenic for a T cell receptor (TCR) that reacts to this peptide contain thymocytes that progress from the immature to the mature phenotype. Intraperitoneal administration of the peptide antigen to transgenic mice results in a rapid deletion of the immature CD4+ CD8+ TCRlo thymocytes. Apoptosis of cortical thymocytes can be seen within 20 hours of treatment. These results provide direct evidence for the in vivo role of apoptosis in the development of antigen-induced tolerance.

Amino Acid Sequence↗
PubMed1990

The neuropharmacology of emesis: the role of receptors in neuromodulation of nausea and vomiting.

The basic pharmacological mechanisms involved in mediating nausea and vomiting are still poorly understood. Several classes of drugs have been identified that alleviate the symptoms of nausea and vomiting, either prophylactically or acutely. None of these is completely effective in all cases. They include antihistamines, dopamine antagonists, steroids, cannabinoids, benzodiazepines, serotonin antagonists, and anticholinergics. This paper examines the evidence that links each of these classes of drugs with the distribution of specific neurotransmitter receptor sites on which they may be acting. Studies on the central nervous system distribution of binding sites for one of these classes of drugs, the anticholinergics, are described. Binding sites for the muscarinic cholinergic radioligand [3H]quinuclidinylbenzilate occur in different concentrations throughout the dorsal vagal complex of the rabbit medulla oblongata. The distribution of such sites in this nonvomiting experimental animal is markedly different from that in the cat, an animal that has been used for many physiological and pharmacological studies of emesis. A previous study has suggested that muscarinic binding sites may occur presynaptically on vagal afferent terminals that synapse in the dorsal vagal complex of the cat; this appears not to be the case in the rabbit. Possible implications of these findings for the identification of the site of action of anticholinergic, antiemetic drugs are discussed.

Animals↗
PubMed1990

Interactional styles of parents following the birth of a high-risk infant.

Using the concept of family management style (FMS) proposed by Knafl & Deatrick (1990), this article illustrates three configurations of defining and managing styles used by dyads in response to the birth of a high-risk infant. The analysis includes a discussion of the applicability of the framework to an acute illness situation.

Adaptation, Psychological↗
PubMed1989

Nodose ganglionectomy selectively reduces muscarinic cholinergic and delta opioid binding sites in the dorsal vagal complex of the cat.

The dorsal vagal complex of the medulla oblongata, comprising the nucleus tractus solitarii, the area postrema and the dorsal motor nucleus of the vagus nerve, is an important brainstem regulatory center for the autonomic nervous system. The major afferent input from abdominal and thoracic viscera to this region is via vagal sensory neurons which have their cell bodies in the nodose ganglion. Autoradiography has been used to study the effects of unilateral nodose ganglionectomy on receptor binding sites in this region of the brain for the neurotransmitters acetylcholine, norepinephrine, and opioids. Nodose ganglionectomy had no discernible effect on alpha 2 noradrenergic ([3H]p-aminoclonidine) or mu opioid [( 3H]Tyr-D-Ala-Gly-(NMePhe)-Gly-ol) binding sites. However, ganglionectomy did produce a 25% decrease in [3H]quinuclidinyl benzilate (muscarinic cholinergic) binding in the subnucleus gelatinosus of the solitary nucleus, and a marked decrease in [3H][D-Pen5]enkephalin (delta opioid) binding in the dorsomedial subnucleus of the nucleus tractus solitarii, ipsilateral to the lesion. These data suggest that muscarinic cholinergic and delta opioid receptors may be present on terminals of vagal afferent neurons that project to these specific brainstem regions. Since these vagal afferent neurons are known to arise, at least in part, from the gastrointestinal tract, it is possible that cholinergic and/or opioid receptors modulate specific autonomic functions associated with gastric sensory information such as satiety or nausea and emesis.

Animals↗
PubMed1989

Peripheral tolerance to allogeneic class II histocompatibility antigens expressed in transgenic mice: evidence against a clonal-deletion mechanism.

To examine the effects of aberrant expression of class II major histocompatibility complex (MHC) proteins on tolerance development, transgenic mice expressing the I-Ad genes under control of the pancreatic elastase promoter were produced. Such transgenic mice express I-Ad exclusively on exocrine pancreas, without expression in thymus or by lymphocytes. No spontaneous development of autoimmune reactivity toward exocrine pancreas was found in transgene-expressing mice of an H-2b background even though such mice could produce in vitro allogeneic responses against I-Ad. When T cells from nontransgenic H-2b mice as well as transgenic H-2b mice were activated in vitro by I-Ad allogeneic stimulator cells and transferred to transgenic mice, an intense, destructive lymphocytic infiltrate specific for exocrine pancreas developed. These findings suggest that aberrant class II MHC expression alone may not trigger autoimmune reactions. Rather, the unresponsiveness to allogenic class II MHC may result from the inability of exocrine pancreas to initiate primary responses by T cells.

Animals↗
PubMed1989

Differential interaction of guanabenz with receptor binding sites in rat brain and kidney.

The alpha 2-adrenoceptor selective agonist, [3H]guanabenz ([ 3H]GBZ), labels a unique population of binding sites in whole kidney which are not labeled by [3H]p-aminoclonidine ([3H]PAC). These binding sites are saturable and of high affinity (Kd = 10-12 nM). [3H]GBZ was not displaced from these sites by other alpha 1- or alpha 2-ligands, suggesting that they are non-adrenergic. This hypothesis is further supported by the insensitivity of renal guanabenz binding to regulation by guanyl nucleotides or to destruction by trypsin. Also, there appears to be no effect of guanabenz on the potency of isoproterenol in competing for beta-adrenoceptors in the kidney, which has been previously reported to be sensitive to clonidine. The absence of any effect of guanabenz on isoproterenol displacement of [3H]dihydroalprenolol in kidney suggests there are subtle differences in activation of alpha-receptors by clonidine and guanabenz in the kidney. In the brain, [3H]GBZ labels two binding sites. Part of the binding of [3H]GBZ in the brain is to sites essentially identical to the alpha 2-adrenoceptors labeled by [3H]PAC. The remainder of the binding resembles the non-adrenergic binding in kidney. The relationship of this unique binding site to the pharmacologic actions of guanabenz is currently not known.

Animals↗
PubMed1987

Reduced visual acuity in both eyes of monocularly deprived kittens following a short or long period of reverse occlusion.

While there can be substantial recovery of vision during reverse occlusion in the deprived eye of kittens that have been monocularly deprived from birth, in many situations this visual improvement does not appear to be retained following the introduction of binocular visual input. This study examines the consequences of periods of reverse occlusion whose onset and duration would be thought to maximize the opportunity for good and permanent recovery of vision in the initially deprived eye. Twenty kittens were monocularly deprived from near birth to either 4, 5, or 6 weeks of age and then reverse occluded for periods that were either very brief (9-18 d) or very long (9-12 weeks). In the former situation, binocular visual experience was introduced when the visual cortex was most susceptible to environmental modification, which would be thought to maximize the opportunity for the eventual development of good vision in both eyes. On the other hand, the long periods of reverse occlusion might be expected to lead to a permanent recovery of vision in only the initially deprived eye, since binocular visual input would have been introduced at a time when the cortex was no longer very plastic. Surprisingly, the end result of both these extreme regimens of reverse occlusion was the same, namely, a severe bilateral amblyopia in which the acuity of both eyes was permanently reduced to levels that were as low as 1/10, but more typically between 1/3 and 1/4 of normal values. Contrast sensitivity functions measured on 2 of the cats that received a brief period of reverse occlusion revealed deficits in contrast sensitivity of about an order of magnitude at all spatial frequencies. These observations have important implications for the nature of the physiological and anatomical changes that occur in the visual cortex during reverse occlusion.

Animals↗
PubMed1985

Autoradiographic localization of calcium channel antagonist receptors in rat brain with [3H]nitrendipine.

In vitro autoradiographic techniques have been used to localize [3H]nitrendipine binding sites in the rat brain. The superficial cerebral cortex, the ventral, lateral and posterior nuclei of the thalamus, the molecular layer of the dentate gyrus, the substantia nigra and the external plexiform layer of the olfactory bulb, all contain high densities of silver grains. The level of binding sites are greatly reduced in areas low in synaptic connections. The corpus callosum, the fimbria, the alveus hippocampi and the dorsal commissure of the fornix all lack specific silver grains, as does the lateral olfactory tract of the olfactory bulb. Specific silver grains are not found in the habenula or the hypothalamus. Grains are not associated with blood vessel profiles. The discrete localizations of [3H]nitrendipine binding sites suggest a specific synaptic role.

Animals↗
PubMed1985

Determination of residual stresses in denture base polymers using the layer removal technique.

In order to study the influence of residual stresses on dimensional accuracy and mechanical properties of denture bases, an experimental model was devised for measurement of residual stresses in acrylic denture base polymers. Rectangular bar coupons were cut from resin plates heat processed by conventional dental methods. They included samples which had been slow and fast cooled after polymerization and had been stored in dry and wet environments. Uniaxial residual stress distributions for each coupon were disclosed by removing layers of known thicknesses and measuring the ensuing deflection of the specimens. Coupons of a commercial acrylic resin were annealed and used as controls. ANOVA and Scheffe's test were used to compare experimental conditions at the 95% confidence level. Dry specimens exhibited residual surface compressive stresses from 0.43-0.83 MPa (62-120 psi). Water-stored specimens showed higher stress levels, 2.86-3.24 MPa (414-470 psi). Slow cooled pigmented acrylic coupons which were dry showed higher residual stresses compared with other dry but nonpigmented specimens. No significant differences were found between pigmented or clear coupons which contained moisture.

Acrylic Resins↗
PubMed1985

Peripheral-type benzodiazepine receptors in endocrine organs: autoradiographic localization in rat pituitary, adrenal, and testis.

We have used [3H]Ro5-4864, a ligand selective for peripheral-type benzodiazepine receptors, to identify and localize peripheral-type benzodiazepine receptors in endocrine organs. Autoradiographic studies reveal an uniform distribution of [3H]Ro5-4864 binding sites within the anterior, intermediate, and posterior lobes of the pituitary gland, with highest concentrations present in the posterior pituitary. In rat adrenal gland, specific binding sites for [3H]Ro5-4864 are found only in the adrenal cortex, with highest density in the zona glomerulosa and significantly lower concentrations in the zona fasciculata and zona reticularis. [3H]Ro5-4864-associated silver grains in the testis are intensely localized over the interstitial tissue; low concentrations of silver grains are present over the epithelium of the seminiferous tubules but are absent from the tubular lumen. These studies demonstrate a differential and discrete localization of peripheral-type benzodiazepine receptors in rat pituitary, adrenal, and testis.

Adrenal Glands↗
PubMed1985

Detection of acute synthetic vascular graft infection with 111In-labeled leukocyte scanning: an animal study.

Synthetic vascular graft infection is characterized by late diagnosis due to indolent and nonspecific symptoms. Indium-111-labeled leukocyte imaging holds promise as a diagnostic tool to identify vascular graft infection, but reported data on its accuracy are somewhat sparse and conflicting. In this study, 13 mongrel dogs received Dacron aortic interposition grafts. Seven grafts were contaminated at the time of surgery by topical ATCC Staphylococcus aureus concentrated at 10(8) organisms/ml. Six control animals received no graft contamination. All infected animals were sacrificed on the second postoperative day after 111In leukocyte scanning. The results showed a sensitivity of 71%, specificity of 100%, and accuracy of 85% for the 111In leukocyte study in detecting early graft infections; false-positive leukocyte scans in the early postoperative period were not a problem as has been reported by others. These data indicate that leukocyte scanning for graft infection detection is likely to be clinically valuable.

Animals↗
PubMed1984

Endotracheal bretylium tosylate in a canine model.

This study was conducted to determine whether bretylium tosylate (BT) is effectively and safely absorbed through the endotracheal route in the canine model. Eleven adult mongrel dogs were anesthetized with pentobarbital, were orally intubated, and had continuous blood pressure and electrocardiographic monitoring. Four dogs received 5 mg/kg BT, three dogs received 10 mg/kg BT, two dogs received 20 mg/kg BT, and two control dogs were given volumes of normal saline equal to those given the 5- and 10-mg/kg groups. Each dog received the same dose of BT both endotracheally and intravenously, but in a random order and on different dates. Following each drug administration arterial blood was drawn at various intervals over two hours and sent for immediate gas analysis; serum samples were frozen for future determination of BT levels. Regardless of the amounts delivered, the peak levels of BT in the arterial blood following administration by the endotracheal route were consistently low (4.13 micrograms/mL to 14.00 micrograms/mL) when compared to those levels following intravenously administered BT (120 micrograms/mL to 268 micrograms/mL) (all P less than .002 for the 5- and 10-mg/kg groups). No depot effect was observed during a two-hour period. The arterial blood gases did not change significantly following the administration of BT by the endotracheal route in the 5- and 10-mg/kg groups, and sections of these autopsied dog lungs showed no apparent pathologic changes.

Animals↗
PubMed1984

Labile nature of the visual recovery promoted by reverse occlusion in monocularly deprived kittens.

Kittens were monocularly deprived by closing one eye at the time of natural eye opening for periods that ranged from 4 to 14 weeks. This eye was then opened, and the other eye was closed for an approximately equal period of time. During this period of reverse occlusion, the vision of the initially deprived eye improved from apparent blindness to a level of good visual acuity. Surprisingly, however, this recovery was largely eliminated in only 2 weeks once the initially nondeprived eye was opened to restore visual input to both eyes. This finding has important implications for the nature of the mechanism(s) responsible for the dramatic physiological effects of monocular occlusion on the visual cortex. It may also help to elucidate recent observations on patching therapy in human amblyopia.

Amblyopia↗
PubMed1984

Calcium channel blockade: possible explanation for thioridazine's peripheral side effects.

The authors show that thioridazine possesses calcium antagonist activity which may relate to its cardiac and sexual side effects. Binding sites associated with voltage-operated calcium channels were labeled by 3H-nitrendipine. Thioridazine influenced this binding of 3H-nitrendipine in a fashion similar to known calcium antagonists such as verapamil. Thioridazine also antagonized potassium-induced, calcium-dependent contractions of rat vas deferens, with similar potency. Thioridazine concentrations that exert calcium channel antagonist effects correspond to blood levels at therapeutic doses.

Animals↗
PubMed1984

Peripheral-type benzodiazepine receptors in the central nervous system: localization to olfactory nerves.

Binding levels of [3H]Ro5-4864, a ligand selective for peripheral-type benzodiazepine receptors, are substantially higher in homogenates of the olfactory bulb than in the rest of the brain. Among peripheral tissues evaluated, high levels of [3H]Ro5-4864 binding are found in the nasal epithelium. Drug displacement studies show that these binding sites are pharmacologically of the peripheral type. Their presence in the nasal epithelium and in the olfactory bulb can be demonstrated in several different mammalian species. Autoradiographic studies of murine nose reveal a bipolar staining pattern around the cell bodies of the olfactory receptor cells, suggesting the presence of peripheral-type benzodiazepine receptors on both processes of these bipolar neurons. In the brain a high density of [3H]Ro5-4864 binding sites occurs in the nerve fiber and glomerular layers of the olfactory bulb. Throughout the rest of the brain [3H]Ro5-4864-associated silver grains are diffusely distributed with intense staining over the choroid plexus and along the ependymal linings of the ventricles. Both the distribution and the ontogenic development of the peripheral-type benzodiazepine receptors differ from the central-type receptors. Intranasal irrigation with 5% ZnSO4 results in a 50% reduction of peripheral-type benzodiazepine receptors in the olfactory bulb without affecting the density of central-type benzodiazepine receptors. Thus, [3H]Ro5-4864 binding sites in the olfactory bulb appear in large part to be localized to olfactory nerves which originate in the nasal epithelium.

Animals↗
PubMed1984

Tissue heterogeneity of calcium channel antagonist binding sites labeled by [3H]nitrendipine.

Calcium channel antagonist binding sites have been labeled in cerebral cortex, heart, ileum, and skeletal muscle with [3H]nitrendipine. While the dissociation constants of the site from cortex, heart, and ileum are similar, KD approximately equal to 0.1-0.2 nM, the value in skeletal muscle is 2 nM. This difference is affinity is also reflected in the Ki values of dihydropyridine calcium channel antagonists, nifedipine, nimodipine, PY108068, SKF24260, and nisoldipine, and the calcium channel agonist CGP 28392, all of which show lower affinity for the skeletal muscle binding site. The diphenylalkylamine calcium channel antagonists, lidoflazine, cinnarizine, flunarizine, and prenylamine, however, show a 3- to 10-fold increase in affinity in skeletal muscle relative to the other three tissues. EDTA treatment of membranes decreases binding in cortex, heart, and ileum but increases binding in skeletal muscle. These changes are reversible upon addition of CaCl2, SrCl2, or BaCl2. The different properties of [3H]nitrendipine binding in various tissues may relate to the varying tissue sensitivity to organic calcium channel antagonists.

Animals↗