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Biomedical subjects

J W Sharp

Publications and source records attributed to J W Sharp.

At least 19 recordsLinked to original sources
PubMed1999

The neuron-specific K-Cl cotransporter, KCC2. Antibody development and initial characterization of the protein.

The neuron-specific K-Cl cotransporter (KCC2) is hypothesized to function as an active Cl- extrusion pathway important in postsynaptic inhibition mediated by ligand-gated anion channels, like gamma-aminobutyric acid type A (GABAA) and glycine receptors. To understand better the functional role of KCC2 in the nervous system, we developed polyclonal antibodies to a KCC2 fusion protein and used these antibodies to characterize and localize KCC2 in the rat cerebellum. The antibodies specifically recognized the KCC2 protein which is an approximately 140-kDa glycoprotein detectable only within the central nervous system. The KCC2 protein displayed a robust and punctate distribution in primary cultured retinal amacrine cells known to form exclusively GABAAergic synapses in culture. In immunolocalization studies, KCC2 was absent from axons and glia but was highly expressed at neuronal somata and dendrites, indicating a specific postsynaptic distribution of the protein. In the granule cell layer, KCC2 exhibited a distinct colocalization with the beta2/beta3-subunits of the GABAA receptor at the plasma membrane of granule cell somata and at cerebellar glomeruli. KCC2 lightly labeled the plasma membrane of Purkinje cell somata. Within the molecular layer, KCC2 exhibited a distinctly punctate distribution along dendrites, indicating it may be highly localized at inhibitory synapses along these processes. The distinct postsynaptic localization of KCC2 and its colocalization with GABAA receptor in the cerebellum are consistent with the putative role of KCC2 in neuronal Cl- extrusion and postsynaptic inhibition.

Animals↗
PubMed1997

Phencyclidine (PCP) acts at sigma sites to induce c-fos gene expression.

Phencyclidine (PCP) is a compound that results in abnormal human behavior and has been proposed as a chemical model for schizophrenia. It was hypothesized that PCP induction of the immediate-early gene, c-fos, should be seen in areas associated with emotional behavior, such as the cortex and limbic system. It was also proposed that PCP may induce c-fos via the sigma receptor. PCP and two sigma ligands, 1,3-di(2-tolyl)guanidine (DTG) and pentazocine, were shown to induce c-fos in similar patterns. The three compounds abundantly induced c-fos in the cingulate, parietal, and piriform cortices and the midline structures of the thalamus and hypothalamus. Neither PCP nor the sigma ligands induced c-fos in the hippocampus. This suggests that PCP binding at NMDA receptors does not result in significant c-fos induction. Rimcazole, a putative sigma2 receptor antagonist, and other sigma ligands have been shown to ameliorate PCP stereotypic behavior. Rimcazole inhibited PCP c-fos induction in the cingulate and parietal cortices and DTG c-fos induction in the cingulate cortex. DTG shows both sigma1 and sigma2 binding affinity. Rimcazole failed to inhibit pentazocine c-fos induction. Pentazocine binds only to sigma1 receptors. This suggests that PCP may produce a significant fraction of its c-fos induction via sigma2 receptors.

Animals↗
PubMed1996

PCP and ketamine inhibit non-NMDA glutamate receptor mediated hsp70 induction.

The physiological model for glutamate receptor mediated excitotoxicity entails elevation of intraneuronal calcium levels. Excessive activation of the NMDA receptor leads to excitotoxicity by prolonged calcium influx via its calcium channel. The purpose of this research was to examine the mechanism of non-NMDA glutamate receptor mediated excitotoxicity. Mammalian AMPA receptors do not show significant calcium conductance. However, some kainate receptors show significant calcium conductance. The hypothesis of this research states that non-NMDA glutamate agonists (quisqualate (5 microliters of 2 mg/ml i.c.v.), AMPA (4 microliters of 1 mg/ml i.c.v.), and kainate (15 mg/kg i.p.)) produce significant heat shock gene, hsp70, induction via glutamate release with subsequent opening of the NMDA receptor calcium channel. PCP (phencyclidine) and ketamine are noncompetitive blockers of the NMDA calcium channel. They act to prevent significant NMDA receptor excitotoxicity. PCP (20 mg/kg i.p.) and ketamine (60 mg/kg i.p.) both diminished quisqualate and AMPA hsp70 induction in the CA1, CA2, CA3 areas of the hippocampus, in the polymorph area of the dentate gyrus, and in the parietal neocortex. PCP significantly (P < 0.05) diminished kainate hsp70 induction only in the CA1 area and the neocortex. Ketamine failed to reduce kainate hsp70 induction. AMPA receptors appear to result in excitotoxic damage via glutamate release. Glutamate opens NMDA receptor calcium channels which increases intraneuronal calcium levels. Kainate receptors probably mediate excitotoxicity via direct calcium conductance with glutamate release being important in the CA1 area and neocortex.

Animals↗
PubMed1996

Effects of sigma ligands on the ability of rimcazole to inhibit PCP hsp70 induction.

Phencyclidine (PCP) can result in schizophrenia-like behavior. It binds at the PCP site on the NMDA-receptor calcium channel and at the sigma receptor. PCP also induces the heat shock gene hsp7O in retrosplenial cortex neurons. An antipsychotic drug, rimcazole, inhibits PCP hsp7O induction. Rimcazole binds predominantly to sigma-2 sites. It is hypothesized that sigma ligands without antipsychotic properties and with some sigma-2 affinity should partially reverse the effects of rimcazole. (+)-3-PPP, (+)-cyclazocine, and (+)-pentazocine bind predominantly to sigma-I sites. (+)-3-PPP is also a modest sigma-2 ligand. Female Sprague-Dawley rats (200-260 g) were injected intraperitoneally (IP) with (+)-3-PPP (50 mg/kg), rimcazole (60 mg/kg) and, after 5 min, with PCP (40 mg/kg). Brains were sectioned (100 mu m) and presence of the hsp7O gene protein product, HSP7O, was determined immunocytochemically. (+)-3-PPP significantly (0 <0.05) diminished the ability of rimcazole to inhibit PCP hsp7O induction in the retrosplenial cortex. (+)-Cyclazocine (15mg/kg, IP) and (+)-pentazocine (8Omg/kg, IP) given in an analogous manner did not diminish the ability of rimcazole to inhibit PCP hsp7O induction.

Animals↗
PubMed1995

DNQX inhibits phencyclidine (PCP) and ketamine induction of the hsp70 heat shock gene in the rat cingulate and retrosplenial cortex.

Phencyclidine (PCP) and ketamine are known to block NMDA receptor mediated excitotoxicity by non-competitively blocking the NMDA receptor calcium channel. PCP and ketamine have the paradoxical effect of also inducing the heat shock gene, hsp70, in the cingulate and retrosplenial cortex of the rat. The present study shows that DNQX, a specific AMPA receptor antagonist, given as either a 5 mg/kg or 10 mg/kg intraperitoneal dose or into the lateral cerebral ventricle (5 microliters of 0.5 mg/ml) significantly diminished PCP (40 mg/kg) and ketamine (80, 100, 120 mg/kg) hsp70 induction in the posterior cingulate and retrosplenial cortex. The most dramatic decrease of hsp70 induction was seen with the intraventricular dose of DNQX. Present findings show that the AMPA receptor has a role in PCP/ketamine induction of hsp70 in the cortex. DNQX inhibition of PCP/ketamine hsp70 induction was likely related to AMPA receptor antagonism which prevented excess calcium influx via voltage-gated calcium channels.

Animals↗
PubMed1995

Utilization of high molecular weight cytokeratin on prostate needle biopsies in an independent laboratory.

OBJECTIVES: Immunoperoxidase staining of prostate tissues with antibodies to high molecular weight cytokeratin, which selectively labels basal cells, has recently been shown to be useful in the diagnosis of prostate cancer in academic centers. A growing sector in pathology is large independent laboratories, where little is known regarding practice patterns. The following study evaluated the use of high molecular weight cytokeratin in an independent laboratory specializing in prostate needle biopsies. METHODS: In a 2-month period (July 1, 1994 to August 31, 1994), 4047 prostate needle biopsies were evaluated. RESULTS: Without the use of ancillary studies, 2710 (67%) were diagnosed as benign, 978 (24.1%) were diagnosed as cancer, and 23 (0.6%) were diagnosed as high-grade prostate intraepithelial neoplasia. The remaining 336 atypical cases (8.3%) were further evaluated with antibodies to higher molecular weight keratin. Of the 336 cases, 253 (6.2% of total) were resolved as diagnostic for cancer, 68 (1.7% of total) were diagnosed as benign, and 15 (0.4% of total) remained atypical. The cost of performing high molecular weight cytokeratin was approximately $5.00 per case, which was not passed on to the patient. CONCLUSIONS: The use of high molecular weight cytokeratin decreased the rate of an atypical prostate biopsy from 8.3% to 0.4% at a negligible cost to the pathologist and patient.

Biopsy, Needle↗
PubMed1993

Expanding the definition of quality of life for prostate cancer.

BACKGROUND: Quality of life in prostate cancer is a multidimensional concept. From a social work perspective, three quality-of-life issues require additional consideration. These are: the impact of the disease and its treatment on family caregivers, the possibility of age bias and ethical dilemmas in treatment decisions, and the specific concerns of black men in whom the disease is more common. METHODS: Oncology and social work literature was reviewed. RESULTS: Studies of caregivers of elderly patients contribute to understanding the stress and anxieties of families, one of whose members has prostate cancer as a chronic illness. Current debates on expectant management and advanced directives provoke ethical concerns about when to treat prostate cancer especially in elderly patients. A growing appreciation of black health practices and social supports must be considered along with the socioeconomic factors that may inhibit or promote access to care. CONCLUSIONS: Social workers can assist the treatment team in understanding the importance of these factors for specific patients. Additional research is needed on the effect of these issues on access to care, physician-patient-family communication, long-term treatment plans, and outcome.

Black or African American↗
PubMed1993

Elderly men with cancer: social work interventions in prostate cancer.

Prostate cancer requires the attention of social workers in health care for three reasons: the growing elderly population which will increase the number diagnosed, the recent introduction of new treatments and the lack of social acceptability for this condition. Interventions for prostate cancer are specific to the stage of the disease. These individual, family and group interventions are a model for social work services to elderly men with other forms of cancer. Social workers have opportunity to research quality of life and decision-making issues to enhance medical practise in prostate cancer.

Adaptation, Psychological↗
PubMed1992

Dorsal nerve root origins of the cutaneous nerves of the feline pelvic limb.

The dorsal root origins of cutaneous nerves supplying the feline pelvic limb were determined electrophysiologically in 11 cats. Cutaneous nerves were surgically exposed and the presence or absence of an evoked potential in response to stimulation of individual dorsal roots was noted. The dorsal cutaneous branches of L3-L5 and S3, and the lateral cutaneous branch of L3 each arose solely from their parent spinal nerves. The L7, S1, and S2 dorsal cutaneous branches had multiple dorsal root origins. The lateral cutaneous femoral nerve originated from L3-L6 dorsal roots in 4 patterns of origin, and the saphenous nerve originated from L4-L6 dorsal roots in 2 patterns of origin. The lateral and caudal cutaneous sural nerves originated from L6-S1 roots in 2 and 3 patterns, respectively. The lateral and medial plantar nerves arose from L6-S2 roots in 4 and 2 patterns, respectively. The superficial and deep peroneal nerves originated from L6-S1 roots in 2 and 3 patterns, respectively. The caudal cutaneous femoral nerve or its branches arose from L7-S3 in 8 origin patterns. The dorsal nerve of the penis and the superficial perineal nerve arose from L7-S3 and S1-S3 roots, respectively, each in 4 patterns. A subtle correlation between plexus type and dorsal root origins of the cutaneous nerves was noted.

Animals↗
PubMed1991

Hospital utilization for AIDS: are all hospital days necessary?

This study examined hospital utilization and, specifically, unnecessary hospital days for patients with acquired immunodeficiency syndrome (AIDS) in a Midwest regional referral center as of June 1987. In 1990 a follow-up study was conducted to measure changes in length of stay (LOS) and unnecessary days. Results show a mean LOS consistent with other studies and a pattern of unnecessary days comprising 14% to 18% respectively of the mean LOS. Admissions in which the patient died and those considered outliers (LOS greater than 36 days) had a trend toward a higher percentage of unnecessary days. Hospital utilization and unnecessary days for patients with AIDS should be an ongoing quality indicator for hospitals experiencing a high volume of persons with AIDS admissions.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Spinal root origin of the radial nerve and nerves innervating shoulder muscles of the dog.

The ventral spinal root origin of the radial nerve, its muscle branches, and brachial plexus nerves which supply shoulder and thoracic musculature was determined in the dog. Electrophysiological signal averaging techniques measured evoked potential from specific ventral spinal roots to individual muscle nerves. The entire radial nerve received input from the sixth cervical (C6) through the second thoracic (T2) spinal roots. The most significant (p less than .05) input to triceps brachii came from C8 while the deep ramus of the radial nerve received its largest input from C7. The brachiocephalicus, suprascapular, and subscapular nerves all received their most significant (p less than .05) innervation from C6. Approximately 90% of the evoked potential to the axillary nerve originated from C7. The thoracodorsal nerve received most of its innervation from ventral roots C7 and C8. The lateral thoracic nerve which innervates the cutaneous trunci muscle was supplied by ventral roots C8-T2. Examination of innervation patterns suggests that only modest variation of spinal root input to specific nerves occurred between individual dogs.

Animals↗
PubMed1990

The NMDA receptor mediates cortical induction of fos and fos-related antigens following cortical injury.

Cortical cavity lesions and lateral ventricular injections of quinolinic acid, a NMDA receptor agonist, induce Fos and Fos-related antigens (FRAs) throughout ipsilateral adult rat brain cortex in similar patterns. c-fos mRNA, assessed using in situ hybridization, was induced by 1 h and disappeared between 3 and 8 h following cortical lesions. Fos proteins, detected using a specific monoclonal antibody, were induced by 1 h and disappeared by 4 h after cortical lesions. FRA proteins, detected using polyclonal antibodies, were induced between 1 and 4 h and persisted for at least 72 h following focal cortical injury. Intraventricular injections of CPP, a competitive NMDA receptor antagonist, completely blocked the induction of these nuclear proteins in cortex ipsilateral to the focal cortical lesions--except around the injury site itself. Intraventricular injections of quisqualate, a non-NMDA glutamate analogue, induced Fos in hippocampus but not in cortex. These data show that NMDA receptors mediate the induction of Fos and FRAs following cortical injury. It is proposed that local cortical injury releases excitatory amino acids that act at NMDA receptors to initiate spreading depression and that the resultant depolarization induces Fos in neurons throughout the cortex. Since Fos and FRAs are proteins that regulate the expression of target genes, they could mediate long-term biochemical adaptations in neurons following cortical injury.

Animals↗
PubMed1990

Spinal nerve root origin of the median, ulnar and musculocutaneous nerves and their muscle nerve branches to the canine forelimb.

The contribution individual ventral spinal nerve roots made to the canine median nerve, ulnar nerve, musculocutaneous nerve, and their muscle nerve branches was determined electrophysiologically. Each spinal nerve root was sequentially stimulated. Utilizing quantitative signal averaging techniques, the evoked potential was measured at each tested peripheral nerve. Evoked potential to the median nerve originated from the seventh cervical spinal root (C7) through the second thoracic spinal root (T2) with most input from C8 and T1. The ulnar nerve received evoked potential from C7-T2. Although T1 provided the major input to both the median and ulnar nerves, the relative contribution of T1 was greater in the ulnar nerve. The musculocutaneous nerve received input from ventral spinal roots C6-T1 with C6 and C7 providing most of the evoked potential. The ventral spinal roots which supplied the bulk of the evoked potential to a particular muscle nerve were consistent between individual dogs. Variation of evoked potential input was greatest from spinal roots which supplied less than 10% of the total potential.

Animals↗
PubMed1989

c-fos expression and (14C) 2-deoxyglucose uptake in the caudal cerebellum of the rat during motor/sensory cortex stimulation.

Fos, the protein product of the c-fos gene, is induced in neurons in response to a variety of stimuli. In order to see if Fos could be used to map activity in the brain, the pattern of Fos staining was compared to the pattern of (14C) 2-deoxyglucose (2DG) uptake in the seventh and eighth lobules of the cerebellum during electrical stimulation of the cerebral cortex. Electrical stimulation of hindlimb motor/sensory cortex of awake rats increased 2DG uptake in the contralateral and ipsilateral cerebellum. The largest increases occurred in granule cell patches in the contralateral copula pyramidis (Cop P) and pyramis (P), the hemispheric and vermal portions of the eighth cerebellar lobule, respectively. The granule cell patches formed parasagittal bands that extended short distances mediolaterally, and extended long distances anteroposteriorly over much of the Cop P. Forelimb motor/sensory cortex stimulation increased 2DG uptake bilaterally in the seventh, paramedian (PM) cerebellar lobule. The greatest increases occurred in the granule cell layer contralateral to the stimulation. These and the above results generally agree with classical studies that localize forelimb on the seventh lobule anterior to the hindlimb on the eighth lobule. However, hindlimb cortical stimulation activated parts of the PM, and forelimb cortical stimulation activated portions of the rostral Cop P. In general, nonoverlapping portions of Cop P and PM were activated during the two types of cortical stimulation. These results are consistent with a fractured somatotopy (Welker and Shambes, '85) in which nonadjacent body parts are consistently represented in adjacent granule cell patches on each lobule, with the fractured somatotopy being different for every lobule. No region of cerebellum expressed Fos in unstimulated, electrode implanted, control subjects. However, following 15 minutes of electrical stimulation of hindlimb cortex, Fos was expressed 4 hours later in patches of granule cell nuclei in Cop P and P. These patches of Fos immunostained granule cells occurred in similar locations in Cop P to the patches of highest glucose metabolism observed with the 2DG method. Zones of Purkinje cell nuclei also expressed Fos. These Purkinje cell zones were often directly over similar sized granule cell patches in P. In the hemisphere however, the zones of Purkinje cells in ventrolateral Cop P expressing Fos only partially overlapped underlying granule cell patches that expressed Fos. Moreover, Fos was not unduced in any Purkinje cells adjacent to the Fos- stained granule cell patch in dorsolateral Cop P.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Common fur and mystacial vibrissae parallel sensory pathways: 14 C 2-deoxyglucose and WGA-HRP studies in the rat.

Stimulation of mystacial vibrissae in rows A,B, and C increased (14C) 2-deoxyglucose (2DG) uptake in spinal trigeminal nucleus pars caudalis (Sp5c) mostly in ventral portions of laminae III-IV with less activation of II and V. Stimulation of common fur above the whiskers mainly activated lamina II, with less activation in deeper layers. The patterns of activation were compatible with an inverted head, onion skin Sp5c somatotopy. Wheatgerm Agglutinin-Horseradish Peroxidase (WGA-HRP) injections into common fur between mystacial vibrissae rows A-B and B-C led to anterograde transganglionic labeling only of Sp5c, mainly of lamina II with less label in layer V, and very sparse label in III and IV. WGA-HRP skin injections appear to primarily label small fibers, which along with larger fibers, were metabolically activated during common fur stimulation. Mystacial vibrissae stimulation increased 2DG uptake in ventral ipsilateral spinal trigeminal nuclei pars interpolaris (Sp5i) and oralis (Sp5o) and principal trigeminal sensory nucleus (Pr5). Common fur stimulation above the whiskers slightly increased 2DG uptake in ventral Sp5i, Sp5o, and possibly Pr5. The most dorsal aspect of the ventroposteromedial (VPM) nucleus of thalamus was activated contralateral to whisker stimulation. Stimulation of the common fur dorsal to the whiskers activated a region of dorsal VPM caudal to the VPM region activated during whisker stimulation. This is consistent with previous data showing that ventral whiskers and portions of the face are represented rostrally in VPM, and more dorsal whiskers and dorsal portions of the face are represented progressively more caudally in VPM. Mystacial vibrissae stimulation activated the contralateral primary sensory SI barrelfield cortex and a separate region in the second somatosensory SII cortex. Common fur stimulation above the whiskers activated a cortical region between the SI and SII whisker activated regions of cortex. It is proposed that this region represented the combined SI and SII common fur regions of somatosensory neocortex. Both whisker and common fur stimulation activated all layers of cortex, with layer IV being most activated followed by II-III, V, and VI. These data indicate that sensory input from the mystacial vibrissae in the adult rat is processed in brainstem, thalamic, and cortical pathways which are predominantly parallel to those which process information from the neighboring common fur sensory receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Decreases of cortical and thalamic glucose metabolism produced by parietal cortex stimulation in the rat.

Parietal cortex stimulation elicited focal decreases as well as increases of brain glucose metabolism in ipsilateral cortex, ipsilateral thalamus, and contralateral cortex of rats in a pattern resembling 'surround inhibition'. It is proposed that parietal stimulation activated inhibitory circuits which decreased cortical and thalamic glucose metabolism. This decrease of cerebral glucose metabolism is important for interpreting brain glucose metabolic studies particularly when metabolic changes do not correlate with changes of neuronal activity.

Animals↗