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Biomedical subjects

K Fisher

Publications and source records attributed to K Fisher.

At least 55 records · Page 3Linked to original sources
PubMed1998

In vivo antinociceptive activity of anti-rat mGluR1 and mGluR5 antibodies in rats.

To examine the specific roles of group I metabotropic glutamate receptors (mGluRs) in nociceptive processing, we examined the effects of intrathecal (i.t.) treatment with antibodies raised against the C-terminals of mGluR1 and mGluR5 in various rat pain models. The effects of anti-mGluR1 IgG and anti-mGluR5 IgG were assessed in a model of persistent pain induced by intrathecal administration of the mGluR1/5 agonist DHPG, as well as in models of heat pain (plantar test), chemical pain (formalin test) and neuropathic pain. DHPG-induced spontaneous nociceptive behaviours (SNB) were significantly attenuated by i.t. treatment with either anti-mGluR1 IgG (30 microg) or anti-mGluR5 IgG (10 and 30 microg). Neither anti-mGluR1 IgG (30 microg) nor anti-mGluR5 IgG (30 microg) significantly increased response latencies to noxious heat in the plantar test, compared with anti-rat IgG (control IgG). Moreover, neither antibody (30 microg) significantly reduced formalin pain scores as compared to control IgG. However, i.t. treatment with anti-mGluR1 IgG (30 microg) or anti-mGluR5 IgG (30 microg) significantly reduced cold hypersensitivity exhibited 8 days after constriction injury of the sciatic nerve, supporting the contention that group I mGluRs play a role in the development of neuropathic pain. Because these antibodies were effective against neuropathic pain, and not acute heat or chemical noxious stimuli, these results suggest that mGluRs are involved in nociceptive processing in chronic pain states rather than signaling acute noxious stimuli, and that DHPG-induced pain may be mediated by similar mechanisms as neuropathic pain.

Analgesics↗
PubMed1998

Body image and patients with amputations: does the prosthesis maintain the balance?

This paper attempts to establish whether dissatisfaction with the artificial limb and/or body image relate to achieved mobility following lower limb amputation in established limb wearers. Patients attending limb fitting clinics (n = 107, 62% male, mean time from amputation 13.9 years; range 1-54) participated. The measures were a specially designed Attitude to Artificial Limbs Questionnaire, a Body Image Questionnaire adapted from an eating disorders instrument including reference to body shape, the Hospital Anxiety and Depression Scale and the Harold Wood Stanmore Mobility Scale. The rehabilitation physician rated prosthetic suitability on a Numerical Rating Scale. The results showed patients were moderately satisfied with their artificial limb, had little experience of body image disruption or distress and there was no overall relationship between these variables and mobility. However, those with a more negative body image were more anxious and in younger patients who sustained more traumatic than vascular amputations, the correlation between body image and mobility was significant, anxiety was higher and physician satisfaction with the prosthesis was lower. It is concluded that body image disruption, anxiety and depression are not common in established limb wearers except in young people with traumatic amputations.

Adult↗
PubMed1998

Engineering quality through organization change: a study of patient care initiatives by teams.

This report presents a summary and analysis of the continuous quality improvement and organizational change and redesign initiatives undertaken by the unit and service boards organized under the auspices of the HORIZONS Project. Board initiatives were identified and summarized by staff through interviews with the chairpersons and representatives of the boards and review of records. Forty-nine projects from the three pilot units were identified. Each project was classified according to outcome--positive, negative, mixed, and unknown. Sixty percent of initiatives had positive outcomes, and only three initiatives (6%) were negative. Case characteristics were summarized according to board identification, problem, outcome indicators, data baseline, proposed and selected solutions, implementation strategy, monitoring plan, results, change issues, and lessons learned. The study concludes that the board initiatives embody the HORIZONS Projects approach to improving patient care and improving quality of working life for staff and doing so in a budget-neutral manner. The HORIZONS boards process has moved the organization toward more open, collaborative forms of decision making than hitherto practiced.

Cooperative Behavior↗
PubMed1998

Bronchiolitis obliterans after lung transplantation: detection using expiratory HRCT.

OBJECTIVE: The objective of this study was to determine if air trapping, as detected on expiratory high-resolution CT (HRCT), is useful as an indicator of bronchiolitis obliterans (BO) in lung transplant recipients. MATERIALS AND METHODS: Corresponding inspiratory and expiratory HRCT images at five different levels and spirometry were obtained in 21 lung transplant recipients. Eleven patients had BO proved by transbronchial biopsy specimens; the remaining 10 patients had no pathologic or functional evidence of airways disease. Two "blinded" observers assessed the inspiratory images for the presence of bronchiectasis and mosaic pattern of lung attenuation, and the expiratory images for presence and extent of air trapping. Statistical comparison of the frequency of HRCT findings between patients with and without BO was performed using Fisher's Exact Test. RESULTS: On inspiratory images, bronchiectasis and mosaic pattern of lung attenuation were present in 4 (36%) and 7 (64%) of 11 patients with BO, and 2 (20%) and 1 (10%) of 10 patients without BO (p>0.05 and p<0.05), respectively. The sensitivity, specificity, and accuracy of bronchiectasis and mosaic pattern for BO were 36%, 80%, and 57%, and 64%, 90%, and 70%, respectively. On expiratory images, air trapping was found in 10 of 11 (91%) patients with BO compared to 2 of 10 (20%) patients without BO (p<0.002). Air trapping was found to have a sensitivity of 91%, specificity of 80%, and accuracy of 86% for BO. Air trapping was identified in one patient with BO who had normal results of baseline spirometric function tests. CONCLUSION: Air trapping, as detected on expiratory HRCT, was the most sensitive and accurate radiologic indicator of BO in the lung transplant population.

Adult↗
PubMed1997

Evidence for electron transfer-dependent formation of a nitrogenase iron protein-molybdenum-iron protein tight complex. The role of aspartate 39.

Nitrogenase-catalyzed substrate reduction reactions require the association of the iron (Fe) protein and the molybdenum-iron (MoFe) protein, electron transfer from the Fe protein to the MoFe protein coupled to the hydrolysis of MgATP, followed by protein-protein complex dissociation. This work examines the role of MgATP hydrolysis and electron transfer in the dissociation of the Fe protein-MoFe protein complex. Alteration of aspartate 39 to asparagine (D39N) in the nucleotide binding site of Azotobacter vinelandii Fe protein by site-directed mutagenesis resulted in an Fe protein-MoFe protein complex that did not dissociate after electron transfer. While the D39N Fe protein-MoFe protein complex was inactive in all substrate reduction reactions, the complex catalyzed both reductant-dependent and reductant-independent MgATP hydrolysis. Once docked to the MoFe protein, the D39N Fe protein was found to transfer one electron to the MoFe protein requiring MgATP hydrolysis, with an apparent first order rate constant of 0.02 s-1 compared with 140 s-1 for the wild-type Fe protein. Only following electron transfer to the MoFe protein did the D39N Fe protein form a tight complex with the MoFe protein, with no detectable dissociation rate. This was in contrast with the dissociation rate constant of the wild-type Fe protein from the MoFe protein following electron transfer of 5 s-1. Chemically oxidized D39N Fe protein with MgADP-bound did not form a tight complex with the MoFe protein, showing a dissociation rate similar to chemically oxidized wild-type Fe protein (3 s-1 for D39N Fe protein and 6 s-1 for wild-type Fe protein). These results suggest that electron transfer from the Fe protein to the MoFe protein within the protein-protein complex normally induces conformational changes which increase the affinity of the Fe protein for the MoFe protein. A model is presented in which Asp-39 participates in a nucleotide signal transduction pathway involved in component protein-protein dissociation.

Adenosine Triphosphate↗
PubMed1997

Engineering tissue-specific expression of a recombinant adenovirus: selective transgene transcription in the pancreas using the amylase promoter.

Recombinant adenovirus accomplishes highly efficient gene transfer in vivo. Adenoviral vectors would be more attractive vehicles for gene therapy if transgene expression was inducible and restricted to the target tissue. In these studies, we hypothesized that selective transgene expression of a recombinant adenovirus could be accomplished by using a tissue-specific promoter of transcription. A replication-defective adenoviral vector was engineered to express the lacZ marker gene under control of the murine pancreatic amylase promoter. Expression of this vector occurred exclusively in the pancreas in neonatal and adult mice, while a similar vector with a constitutive promoter accomplished transgene expression in several organs. Within the adenoviral construct, the amylase promoter retained its ability to be induced by dexamethasone and insulin. This model will serve as a paradigm for selective and inducible adenoviral transgene expression.

Adenoviridae↗
PubMed1997

Ocular siderosis. Diagnosis and management.

PURPOSE: To assist clinicians in the diagnosis and management of ocular siderosis. METHODS: The diagnosis and management of three cases of ocular siderosis secondary to a retained iron-containing intraocular foreign body are described. RESULTS: Noteworthy features included: 1) the characteristic features of a tonic or Adies pupil (one case) and 2) the failure of high-resolution computed tomography scanning and plain film radiography to detect the intraocular foreign body (two of three cases). In contrast, ultrasonography demonstrated the intraocular foreign bodies in all cases and accurately localized them to the inferior retinal quadrants. A third noteworthy finding was that a preoperative electroretinogram reduction in amplitudes of as much as 40% compared with that of the uninvolved eye was compatible with excellent vision, and that the electroretinogram returned to normal after the intraocular foreign body was removed. CONCLUSIONS: Ocular siderosis should be considered in the differential diagnosis of a tonic or Adies pupil. To detect an occult intraocular foreign body, clinicians should not rely exclusively on computed tomography scanning or plain film radiography, but should also use B-mode echography with careful study of the inferior quadrants. In ocular siderosis a preoperative electroretinogram reduction in amplitudes of as much as 40% may be reversible after intraocular foreign body removal.

Adie Syndrome↗
PubMed1997

Childhood hypophosphatasia. A case report.

Hypophosphatasia is a hereditary disease that can present as premature exfoliation of deciduous dentition in young children. We present a case of a 32-month-old female with a history of skeletal problems who spontaneously exfoliated three mandibular primary teeth. It was the premature exfoliation of her mandibular teeth that led to the diagnosis of childhood hypophosphatasia.

Child, Preschool↗
PubMed1997

The effect of accommodative hysteresis on apparent stationarity.

The potential contribution of accommodation to the ability to perceive whether an object is moving in space during lateral movement of the head was examined in 16 visually-normal young adults. The target, which provided a highly effective accommodation stimulus, was viewed monocularly in an otherwise completely darkened room. Self-generated head movements of controlled amplitude and frequency were used to produce lateral target motion of continuously variable amplitude either in-phase or counter-phase to the lateral translation of the head. Tonic accommodation and the target/head displacement ratio needed for apparent target stationarity were measured before and after sustained focus at either the nearpoint or farpoint. Tonic accommodation shifted inward under the nearpoint condition and outward under the farpoint condition. The tonic aftereffects induced under the nearpoint and farpoint conditions were accompanied by increases and decreases, respectively, in the degree of positive (same direction as the head) concomitant motion required for apparent target stationarity. These results suggest that the altered accommodative effort required to compensate for the tonic aftereffects influenced the magnitude of the absolute visual parallax ascribed to self-motion. The accommodative system therefore appears to contribute to position constancy, at least in a relatively impoverished visual environment.

Accommodation, Ocular↗
PubMed1996

Comparison of nociceptive effects produced by intrathecal administration of mGluR agonists.

The present study examined the mGluR subtypes involved in (1S, 3R)-ACPD-induced spontaneous nociceptive behaviours (SNB) by administering the following selective agonists by the intrathecal (i.t.) route: (RS)-DHPG, trans-ADA (Group I; mGluR1/5 and mGluR5, respectively), (1S, 3S)-ACPD, (2R, 4R)-APDC (Group II), and L-AP4 (Group III). (RS)-DHPG administration induced SNB that were of significantly greater intensity and longer duration than those induced by an equal dose of (1S, 3R)-ACPD. No other agonists produced SNB, except (1S, 3S)-ACPD, which may be attributable to a nonselective action at mGluR1. Intrathecal treatment with the mGluR antagonist (+)-MCPG or the NMDA antagonist D-AP5 prior to (RS)-DHPG administration dose-dependently reduced SNB. It is suggested that a possible interaction between NMDA and mGluR1 is a critical event in the maintenance of persistent nociception.

Animals↗
PubMed1996

Evidence for electron transfer from the nitrogenase iron protein to the molybdenum-iron protein without MgATP hydrolysis: characterization of a tight protein-protein complex.

MgA TP hydrolysis has been proposed to be absolutely required for electron transfer from the nitrogenase iron (Fe) protein to the molybdenum-iron (MoFe) protein. This work presents evidence for primary electron transfer from the Azotobacter vinelandii nitrogenase Fe protein to the MoFe protein in the absence of MgATP hydrolysis. Deletion of an amino acid (Leu 127) in a signal transduction pathway in the Fe protein resulted in an Fe protein conformation resembling the MgATP-bound state. This altered Fe protein (L127delta) was found to bind to the MoFe protein in the absence of MgATP, forming a tight protein complex. Both steady state and stopped-flow transient kinetic measurements suggest that two L127delta Fe proteins bind to one MoFe protein with an extremely high affinity. From pre-steady state kinetic determinations of the rate of complex dissociation, the affinity was found to be at least 350 times tighter than that of the wild-type A. vinelandii nitrogenase complex and at least 20 times tighter than that of the heterologous Clostridium pasteurianum Fe protein-A. vinelandii MoFe protein complex. The L127delta Fe protein-MoFe protein complex was isolated by gel filtration liquid chromatography. Scanning densitometry of an SDS gel of the complex isolated from the gel filtration column revealed a stoichiometry of 1.7 L 127 delta Fe proteins bound per MoFe protein. The L 127 delta Fe protein was found to transfer a single electron from its [4Fe-4S] cluster to the MoFe protein at a rate of 0.2s-1. This compares with the MgATP dependent electron transfer rate of 140 s-1 observed for transfer of an electron from the wild-type Fe protein to the MoFe protein. No substrate reduction (H+ or C2H2) was detected when wild-type MoFe protein was complemented with L 127 delta Fe protein. The MgATP-independent electron transfer from the L 127 delta Fe protein to the MoFe protein required active MoFe protein and was not inhibited by MgADP. EPR spectroscopy of the complex was employed to confirm the electron transfer reaction. These results show that Fe protein in a conformation resembling the MgATP-bound state can transfer at least one electron to the MoFe protein without the need for MgATP hydrolysis.

Acetylene↗
PubMed1996

The contribution of metabotropic glutamate receptors (mGluRs) to formalin-induced nociception.

The present study examined the role of mGluRs in nociceptive responses of male Long-Evans rats following a subcutaneous (s.c.) injection of 1% (30 microliters) or 2.5% (50 microliters) formalin to the plantar surface of the hindpaw. Intrathecal (i.t.) administration of the mGluR4/mGluR6-mGluR8 agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4), the mGluR1/mGluR5 antagonists. (S)-4-carboxyphenylglycine ((S)-4CPG) or (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG), but not the non-selective antagonist, (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG), to the lumbar spinal cord slightly reduced second phase nociceptive responses. An i.t. injection of the mGluR1/mGluR5 agonist, (RS)-3,5-dihydroxyphenylglycine ((RS)-DHPG) or the mGluR2/mGluR3 agonist, (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3S)-ACPD), but not (2S,1'R,2'R,3'R)-2-(2'3-dicarboxy-cyclopropyl)-glycine (DCG-IV), dose-dependently enhanced formalin-induced nociception in the second phase. In addition, the facilitation of nociceptive responses induced by (1S,3S)-ACPD or (RS)-DHPG was reduced by prior i.t. administration of the mGluR antagonists, (+)-MCPG or (S)-4C3HPG, respectively, as well as by the N-Methyl-D-aspartate (NMDA) receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid (D-AP5). These results indicate that although mGluRs may play a minor role in formalin-induced nociception, mGluR agonist-related facilitation of formalin scores may reflect an interaction with the NMDA receptor.

Aminobutyrates↗
PubMed1995

Involvement of the P cluster in intramolecular electron transfer within the nitrogenase MoFe protein.

Nitrogenase is the catalytic component of biological nitrogen fixation, and it is comprised of two component proteins called the Fe protein and MoFe protein. The Fe protein contains a single Fe4S4 cluster, and the MoFe protein contains two metallocluster types called the P cluster (Fe8S8) and FeMo-cofactor (Fe7S9Mo-homocitrate). During turnover, electrons are delivered one at a time from the Fe protein to the MoFe protein in a reaction coupled to component-protein association-dissociation and MgATP hydrolysis. Under conditions of optimum activity, the rate of component-protein dissociation is rate-limiting. The Fe protein's Fe4S4 cluster is the redox entity responsible for intermolecular electron delivery to the MoFe protein, and FeMo-cofactor provides the substrate reduction site. In contrast, the role of the P cluster in catalysis is not well understood although it is believed to be involved in accumulating electrons delivered from the Fe protein and brokering their intramolecular delivery to the substrate reduction site. A nitrogenase component-protein docking model, which is based on the crystallographic structures of the component proteins and which pairs the 2-fold symmetric surface of the Fe protein with the exposed surface of the MoFe protein's pseudosymmetric alpha beta interface, is now available. During component-protein interaction, this model places the P cluster between the Fe protein's Fe4S4 cluster and FeMo-cofactor, which implies that the P cluster is involved in mediating intramolecular electron transfer between the clusters. In the present study, evidence supporting this idea was obtained by demonstrating that it is possible to alter the rate of substrate reduction by perturbing the polypeptide environment between the P cluster and FeMo-cofactor without necessarily disrupting the metallocluster polypeptide environments or altering component-protein interaction.

Amino Acid Sequence↗