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1.
J Laryngol Otol ; 129 Suppl 2: S33-7, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25706158

ABSTRACT

OBJECTIVE: We investigated the ossicular movement in the near-intact middle ear in response to acoustic stimulation using a high-speed video camera and video analysis software program. DESIGN: We have designed a good visual access to the middle ear of the guinea pig by opening the ventral wall of the otic capsule, without injuring the sound-conducting structures, from the external auditory canal to the oval window. The high-speed video camera could record analysable ossicular motion up to 4000 frames per second. RESULTS: The stapes showed reciprocal movement in the same frequency as the stimulating tone, and with an amplitude proportional to the stimulating sound intensity. Injury to the tympanic membrane attenuated the stapedial motion, which was recovered to that of the control level by patch repair of the perforation. CONCLUSION: Our experimental set-up was capable of evaluating the conductive hearing, regardless of the status of the animal's sensorineural hearing or even life. Such a video analysis may provide a powerful tool to investigate the physiology of the middle ear.


Subject(s)
Acoustic Stimulation , Diagnostic Imaging/methods , Microscopy, Video/methods , Oscillometry/methods , Stapes/physiology , Animals , Female , Guinea Pigs , Hearing/physiology , Male , Myringoplasty , Software , Tympanic Membrane/injuries
2.
Exp Clin Endocrinol Diabetes ; 118(7): 405-9, 2010 Jul.
Article in English | MEDLINE | ID: mdl-19856252

ABSTRACT

OBJECTIVE: LHX4, a LIM-homeodomain transcription factor, is required for development of the pituitary and nervous system. Several mutations of the LHX4 gene have been identified in patients with combined pituitary hormone deficiency (CPHD). The objective of the study was to clarify the molecular basis of a Japanese patient of CPHD with a small anterior pituitary and an ectopic posterior pituitary. METHODS: Genomic DNA was extracted from blood samples of the patient. Exons and exon-intron junctions of the LHX4 gene were amplified and sequenced. An expression vector of the mutant LHX4 protein was constructed and its function was analyzed in vitro. RESULTS: A novel missense mutation (V101A) was identified. IN VITRO transfection studies demonstrated that V101A mutant LHX4 was unable to activate the POU1F1 and FSHbeta subunit gene promoter, indicating a loss of function mutation. CONCLUSION: Our results identify a novel loss of function mutation of the LHX4 gene in a Japanese patient with CPHD.


Subject(s)
Homeodomain Proteins/genetics , Hypopituitarism/genetics , Mutation, Missense , Pituitary Hormones, Anterior/deficiency , Pituitary Hormones, Posterior/deficiency , Transcription Factors/genetics , Adolescent , Amino Acid Sequence , Follicle Stimulating Hormone, beta Subunit/genetics , Growth Hormone/therapeutic use , Humans , Hydrocortisone/therapeutic use , Hypopituitarism/drug therapy , LIM-Homeodomain Proteins , Male , Molecular Sequence Data , Testosterone/therapeutic use , Thyroxine/therapeutic use , Transcription Factor Pit-1/genetics , Transcriptional Activation
3.
Neurology ; 68(13): 1062-8, 2007 Mar 27.
Article in English | MEDLINE | ID: mdl-17389313

ABSTRACT

OBJECTIVE: To investigate whether cognitive slowing in Parkinson disease (PD) reflects disruption of the basal ganglia or dysfunction of the frontal lobe by excluding an influence of abnormal brain activity due to motor deficits. METHODS: We measured neuronal activity during a verbal mental-operation task with H(2)(15)O PET. This task enabled us to evaluate brain activity change associated with an increase in the cognitive speed without an influence on motor deficits. RESULTS: As the speed of the verbal mental-operation task increased, healthy controls exhibited proportional increase in activities in the anterior striatum and medial premotor cortex, suggesting the involvement of the corticobasal ganglia circuit in normal performance of the task. By contrast, patients with PD lacked an increase in the striatal activity, whereas the medial premotor cortex showed a proportional increase. CONCLUSIONS: Although the present study chose a liberal threshold and needs subsequent confirmation, the findings suggest that striatal disruption resulting in abnormal processing in the corticobasal ganglia circuit may contribute to cognitive slowing in Parkinson disease, as is the case in motor slowing.


Subject(s)
Cognition Disorders/etiology , Cognition Disorders/physiopathology , Corpus Striatum/physiopathology , Parkinson Disease/complications , Parkinson Disease/psychology , Brain Mapping , Cerebrovascular Circulation/physiology , Cognition Disorders/diagnostic imaging , Corpus Striatum/diagnostic imaging , Female , Humans , Male , Middle Aged , Motor Cortex/physiopathology , Neural Pathways/physiopathology , Neuropsychological Tests , Parkinson Disease/physiopathology , Positron-Emission Tomography , Predictive Value of Tests , Reaction Time/physiology , Reference Values
4.
J Neural Transm (Vienna) ; 114(5): 577-84, 2007.
Article in English | MEDLINE | ID: mdl-17225931

ABSTRACT

The purpose of this study is to identify the underlying differences between patients with white matter lesions (WMLs) who manifested gait disturbance suggestive of vascular parkinsonism (VaP) and those who did not, using the PET scan. Fourteen patients with extensive WMLs, as determined by MRI, were divided into two groups - 7 with gait disturbance and 7 without it. Neuronal integrity was evaluated with a PET scan using [(11)C]flumazenil (FMZ) by calculating the distribution volume of FMZ (FMZ-V(d)) in various regions of interest by non-linear curve fitting. Additionally, tracer kinetic analysis was applied for voxel-by-voxel quantification of FMZ-V(d) and data analysis was performed using statistical parametric mapping. The striatal FMZ-V(d) values were inversely correlated with the motor UPDRS scores (r = 0.70, p < 0.005), and their reductions were associated with the presence of gait disturbance. Therefore, differences in neuronal integrity in the striatum may determine whether patients with WMLs develop VaP or not.


Subject(s)
Basal Ganglia Cerebrovascular Disease/diagnostic imaging , Basal Ganglia/diagnostic imaging , Nerve Degeneration/diagnostic imaging , Parkinsonian Disorders/diagnostic imaging , Aged , Aged, 80 and over , Basal Ganglia/blood supply , Basal Ganglia/pathology , Basal Ganglia Cerebrovascular Disease/pathology , Basal Ganglia Cerebrovascular Disease/physiopathology , Carbon Radioisotopes , Female , Flumazenil , GABA Modulators , Gait Disorders, Neurologic/diagnostic imaging , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Humans , Leg/innervation , Leg/physiopathology , Magnetic Resonance Imaging , Male , Middle Cerebral Artery/pathology , Middle Cerebral Artery/physiopathology , Nerve Degeneration/pathology , Nerve Degeneration/physiopathology , Nerve Fibers, Myelinated/metabolism , Nerve Fibers, Myelinated/pathology , Parkinsonian Disorders/pathology , Parkinsonian Disorders/physiopathology , Positron-Emission Tomography , Predictive Value of Tests
5.
Neurology ; 67(9): 1674-6, 2006 Nov 14.
Article in English | MEDLINE | ID: mdl-17101904

ABSTRACT

We compared the cognitive functions and interictal cerebral glucose metabolism of 11 patients with mesial temporal lobe epilepsy (MTLE) with frequent seizures to those of 10 patients with MTLE with rare seizures; the groups were matched for age, sex, education, IQ, and focus side. The frequent-seizure group had more set-shifting impairment that correlated with glucose hypometabolism in the prefrontal cortices. Our results suggest that frequent seizures in MTLE are associated with hypofunction of the prefrontal cortex.


Subject(s)
Cognition Disorders/etiology , Cognition Disorders/physiopathology , Epilepsy, Temporal Lobe/complications , Epilepsy, Temporal Lobe/physiopathology , Prefrontal Cortex/physiopathology , Adult , Brain Mapping , Cognition Disorders/diagnostic imaging , Energy Metabolism/physiology , Epilepsy/complications , Epilepsy/diagnostic imaging , Epilepsy/physiopathology , Epilepsy, Temporal Lobe/diagnostic imaging , Female , Fluorodeoxyglucose F18 , Functional Laterality/physiology , Glucose/metabolism , Humans , Male , Middle Aged , Neuropsychological Tests , Positron-Emission Tomography , Predictive Value of Tests , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/metabolism , Set, Psychology
6.
Stroke ; 35(4): 942-7, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15001785

ABSTRACT

BACKGROUND AND PURPOSE: [11C]flumazenil (FMZ), a ligand that selectively binds to the central benzodiazepine receptor in the neuronal membrane, is useful for evaluating neuronal viability in a positron emission tomography (PET) scan. Using this ligand, we investigated whether there was a correlation between neuronal integrity in various brain structures and dementia in patients with leukoaraiosis. METHODS: Twelve patients with extensive leukoaraiosis on magnetic resonance imaging were divided into groups of patients with or without dementia. Based on a 2-compartment, 2-parameter model that included metabolite-corrected arterial input and PET-measured cerebral radioactivity, the distribution volume of FMZ (FMZ-V(d)) was calculated in various regions of interest by nonlinear curve fitting. Additionally, tracer kinetic analysis was applied for voxel-by-voxel quantification of FMZ-V(d), and data analysis was performed by statistical parametric mapping. RESULTS: The presence of dementia was associated with a reduced FMZ-V(d) in widespread areas of the cerebral cortex, including the bilateral frontopolar and frontal/insular areas, the left temporo-occipital border areas, and the left marginal cortical areas. CONCLUSIONS: Differences in neuronal integrity in the cerebral cortex might determine whether patients with leukoaraiosis become symptomatic or not.


Subject(s)
Cerebral Cortex/metabolism , Dementia, Vascular/metabolism , Receptors, GABA-A/metabolism , Aged , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Cerebrovascular Circulation , Dementia, Vascular/diagnosis , Dementia, Vascular/diagnostic imaging , Female , Flumazenil/metabolism , Humans , Ligands , Magnetic Resonance Imaging , Male , Oxygen Consumption , Radioactive Tracers , Tomography, Emission-Computed
7.
Nucl Med Biol ; 28(6): 633-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11518644

ABSTRACT

As part of our program of developing PET tracers for neuroimaging of psychotropic compounds, venlafaxine, an antidepressant drug, was evaluated. First, we measured in vitro rates of serotonin uptake in synaptosomes prepared from selected regions of porcine brain. Then, we determined the pharmacokinetics of venlafaxine, [O-methyl-11C]-labeled for PET. Synaptosomal studies showed that the active uptake of [14C]5-HT differed markedly between brain regions, with highest rates in hypothalamus, raphé region, and thalamus, and lowest rates in cortex and cerebellum. PET studies showed that the unidirectional rate of uptake of [O-methyl-11C]venlafaxine from blood to brain was highest in the hypothalamus, raphé region, thalamus and basal ganglia and lowest in the cortex and cerebellum. Under normal physiological conditions, the capillary permeability-surface area (PS) product for [O-methyl-11C]venlafaxine could not be estimated, because of complete flow-limitation of the cerebral uptake. Nevertheless, a correlation occurred between the apparent partition volume of the radiotracer and the rate of active uptake of 5-HT in selected regions of the porcine brain. During hypercapnia, limitations of blood-brain transfer were observed, giving PS-products for water that were only ca. 50% higher than those of venlafaxine. Thus, under normal physiological conditions, the rate of uptake of venlafaxine from blood into brain is completely flow-limited.


Subject(s)
Antidepressive Agents, Second-Generation/pharmacokinetics , Brain/diagnostic imaging , Cyclohexanols/pharmacokinetics , Serotonin/pharmacokinetics , Animals , Brain/metabolism , Carbon Radioisotopes/pharmacokinetics , Cerebrovascular Circulation , Female , Metabolic Clearance Rate , Radiochemistry , Swine , Synaptosomes/metabolism , Tissue Distribution , Tomography, Emission-Computed , Venlafaxine Hydrochloride
8.
Hinyokika Kiyo ; 47(7): 497-9, 2001 Jul.
Article in Japanese | MEDLINE | ID: mdl-11523136

ABSTRACT

A 42-year-old man complained of lower abdominal pain. Computed tomographic scan and magnetic resonance imaging revealed an infected urachal cyst. A drainage catheter, which had multiple holes over a 10 cm length from the catheter tip, was placed in the urachal cyst. The catheter was inserted from the subumbilicus region and the catheter tip was intended to be situated at the caudal end of the urachal cyst. However, the catheter tip accidentally perforated the bladder and urine flowed out of the bladder through the catheter. Because the urine diluted and washed out the pus in the urachal cyst, the infected urachal cyst was successfully drained. Percutaneous drainage and antibiotics allowed resolution of the inflammatory process. On the twenty-third day after catheter placement, excision of the urachal cyst and partial cystectomy were performed with relative ease and without any complications.


Subject(s)
Drainage/methods , Infections/complications , Urachal Cyst/therapy , Urinary Catheterization/methods , Adult , Humans , Male , Urinary Bladder
9.
J Virol ; 75(1): 61-72, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11119574

ABSTRACT

The simian virus 40 capsid is composed of 72 pentamers of VP1 protein. Although the capsid is known to dissociate to pentamers in vitro following simultaneous treatment with reducing and chelating agents, the functional roles of disulfide linkage and calcium ion-mediated interactions are not clear. To elucidate the roles of these interactions, we introduced amino acid substitutions in VP1 at cysteine residues and at residues involved in calcium binding. We expressed the mutant proteins in a baculovirus system and analyzed both their assembly into virus-like particles (VLPs) in insect cells and the disassembly of those VLPs in vitro. We found that disulfide linkages at both Cys-9 and Cys-104 conferred resistance to proteinase K digestion on VLPs, although neither linkage was essential for the formation of VLPs in insect cells. In particular, reduction of the disulfide linkage at Cys-9 was found to be critical for VLP dissociation to VP1 pentamers in the absence of calcium ions, indicating that disulfide linkage at Cys-9 prevents VLP dissociation, probably by increasing the stability of calcium ion binding. We found that amino acid substitutions at carboxy-terminal calcium ion binding sites (Glu-329, Glu-330, and Asp-345) resulted in the frequent formation of unusual tubular particles as well as VLPs in insect cells, indicating that these residues affect the accuracy of capsid assembly. In addition, unexpectedly, amino acid substitutions at any of the calcium ion binding sites tested, especially at Glu-157, resulted in increased stability of VLPs in the absence of calcium ions in vitro. These results suggest that appropriate affinities of calcium ion binding are responsible for both assembly and disassembly of the capsid.


Subject(s)
Calcium/metabolism , Capsid/chemistry , Disulfides/chemistry , Simian virus 40/physiology , Virion/physiology , Virus Assembly , Animals , Binding Sites , Capsid Proteins , Cysteine , Spodoptera , Structure-Activity Relationship
11.
Oncology (Williston Park) ; 14(10 Suppl 9): 87-90, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11098503

ABSTRACT

In a step toward a clinical trial, the tumor response and survival of a weekday-on/weekend-off schedule of UFT was compared with its conventional daily schedule in a cancer-bearing rat model. The dose-intensive schedule--600 mg of UFT for 5 days followed by 2 drug-free days--amounts to a weekly dose similar to the conventional schedule of 400 mg/day. The weekday-on/weekend-off schedule provided increased survival and significantly greater antitumor activity than the conventional daily schedule, with no difference in adverse reactions. A study was also conducted in human subjects to measure fluorouracil (5-FU) concentrations that identified the pharmacokinetic activity during the 2 drug-free days of the weekday-on/weekend-off schedule. The plasma 5-FU concentration declined markedly after 24 hours, but the concentration in the tumor remained at a relatively high level after 2 days off the drug. A one-year clinical study evaluated the compliance and toxicity of the weekday-on/weekend-off UFT schedule as adjuvant chemotherapy for colorectal cancer. Based on the findings of all these studies, the weekday-on/weekend-off schedule for UFT as adjuvant chemotherapy for colorectal cancer can be recommended for a clinical trial.


Subject(s)
Antimetabolites, Antineoplastic/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Fluorouracil/pharmacokinetics , Sarcoma/drug therapy , Administration, Oral , Animals , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Administration Schedule , Humans , Male , Rats , Sarcoma/veterinary , Survival Analysis , Tegafur/administration & dosage , Uracil/administration & dosage
12.
Pathophysiology ; 7(2): 83-89, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10927185

ABSTRACT

Sedimentary calcium carbonate was grown at a physiological pH6.8 from a mixture of equivolume of 70 mM Ca(NO(3))(2) and 70 mM NaHCO(3) aqueous solution. The kinetics of the crystal growth was monitored by means of turbidity measurement. The apparent absorption is gradually increased with the elapsed time after the mixing and reaches its maximum at t(max). The average t(max) is significantly decreased from =467 s (for n=13 runs) to 408 s (n=13) by application of the static magnetic field (SMF) of H=400 mT to the precipitating solution. The application of SMF at 120 s later the mixing shows the same =396 s (n=9) as that of 408 s. It has been thus detected that the application of SMF is ineffective in the stage of the nucleation or the earlier stage of the crystal growth but effective in the Ostwald ripening stage of the growth nucleus or the later stage of the crystal growth where large numbers of the growing crystalline particles seem greater than a few hundred nanometers. A possible mechanism for the SMF effect is as follows. An ion escaping from the growing crystal surface with a certain 'migration velocity' due to a random walk process has significant probability to drift onto the identical surface or at least the identical crystal by means of Lorentz force, because the translational displacement of the crystal during a cycle of the cyclotron motion of the ion is smaller than the size of the growing crystal. This type of drift results in the suppression of re-dissolution of the ions on the growing surface and in the acceleration of the growth in the later stage of the crystal growth. The undetected SMF effect in the earlier stage of the crystal growth can be partly attributed to the re-dissolution due to the thermodynamic instability of the small nuclei which predominates over the presumable SMF effect. This can be partly ascribed to the large translational displacement of the small particle. The application of this mechanism to an oscillating magnetic field will predict the presence of a window for the frequency of the oscillating magnetic field.

13.
Pathophysiology ; 7(2): 91-92, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10927186

ABSTRACT

An idea for a relation between the frequency and intensity of the optimal oscillating magnetic field for the magnetic effects has been presented. An estimated optimal frequency is about 150 Hz for a system containing ions of effective molecular weight of M approximately 100 under a square pulsing magnetic field of intensity H=1 mT.

14.
Pathophysiology ; 7(2): 101-105, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10927188

ABSTRACT

The chickens were raised under fixation of the permanent magnet (80 mT) and the effect of extra magnetic field, which affects on the content of the several inorganic chemical elements of egg shell, was investigated by X-ray fluorescence spectroscopy. From 3 days after fixing the magnet, the relative concentration of Ca begun to increase. After 10 days, the relative contents of Ca were decreased, while conversely the contents of K were increased. Though there was a linear relationship between Ca content and P content in inner layer of chicken egg shell, the relationship was greatly hindered by applying the static magnetic field. The experimental result suggests that both Ca and K ion transport can be perturbed by addition of extra magnetic field in the incubation processes of chicken egg, and that Ca, P and K ions play the important role in egg shell formation.

15.
J Colloid Interface Sci ; 229(1): 165-167, 2000 Sep 01.
Article in English | MEDLINE | ID: mdl-10942554

ABSTRACT

Functionalized polystyrene stars were prepared by copolymerization of polystyryl lithium with divinylbenzene in a mixture of benzene/tetrahydropyran, where the polystyrene arms were prepared by anionic polymerization using [2-[(N,N-dimethylamino)-methyl]phenyl]lithium as the initiator. These functional stars were converted by quaternization with methyl iodide into polystyrene stars having peripheral positive charges. We studied the charge effects on the solution properties of such stars. The hydrodynamic dimension of peripheral charged polystyrene (PS) stars depended strongly on the solubility parameter between PS segments and solvent. Copyright 2000 Academic Press.

16.
Synapse ; 38(1): 87-101, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10941144

ABSTRACT

The ligands N-methylspiperone and haloperidol both bind to D(2)-like dopamine receptors. The competitive nature of the binding over a wide range of haloperidol concentrations and the effect on dopamine release have never been tested in vivo. We determined the competitive interaction between 3-N-[(11)C]methylspiperone ([(11)C]NMSP) and haloperidol binding to striatal dopamine D(2)-like receptors with positron emission tomography (PET) of pig brain. [(11)C]NMSP tomography was performed with haloperidol at five different plasma concentrations maintained constant by programmed infusion. Kinetic parameters of ligand competition for binding in the striatum were determined by deconvolving time-activity curves of the striatum and cerebellum from metabolite-corrected arterial plasma [(11)C]NMSP and haloperidol concentrations. Two types of [(11)C]NMSP-binding sites were evident in the striatum, both saturable by haloperidol administration. The preponderant or primary sites bound [(11)C]NMSP irreversibly, as dopamine D2-like receptors, while the secondary sites bound [(11)C]NMSP reversibly, as do serotonin S2 receptors. Woolf-Hanes plots revealed the predicted approximately linear relationships between the binding indices and the haloperidol plasma concentration. For the irreversible binding sites, this relationship indicated a 50% inhibitory concentration of haloperidol of 2 nM in plasma and a maximum binding capacity of 64 pmol cm(-3) in striatum. For the reversible binding sites, the relationship indicated a 50% inhibitory plasma concentration of haloperidol of 1 nM and a maximum binding capacity of 4.5 pmol cm(-3). Second-order polynomial Eadie-Hofstee-Scatchard plots were consistent with increased competition from an endogenous ligand of the irreversibly binding sites only with increasing doses of haloperidol. At the highest haloperidol dose, this hypothetical endogenous ligand had risen 6-7-fold. We contend that this reveals the release of dopamine by high concentrations of haloperidol.


Subject(s)
Binding, Competitive/drug effects , Haloperidol/pharmacokinetics , Neostriatum/drug effects , Receptors, Dopamine D2/drug effects , Spiperone/analogs & derivatives , Animals , Binding, Competitive/physiology , Carbon Radioisotopes , Female , Neostriatum/diagnostic imaging , Radioligand Assay , Receptors, Dopamine D2/metabolism , Spiperone/pharmacokinetics , Swine , Tomography, Emission-Computed
17.
Acta Otolaryngol Suppl ; 543: 241-3, 2000.
Article in English | MEDLINE | ID: mdl-10909031

ABSTRACT

Subjective tinnitus is an auditory phantom perception that may arise from any aberrant signal within the auditory system. Further processing of this signal and the conscious perception of tinnitus takes place in the cerebral cortex. A few functional brain-imaging studies have been performed to elucidate the underlying cerebral mechanisms of this perception. These studies mostly concern rare types of tinnitus (e.g. tinnitus changeable by oral-facial movements), or compared tinnitus patients with healthy volunteers. These studies attributed variable activation of the primary auditory cortices, associative auditory cortices and the left hippocampus to the perception of tinnitus. Based on these heterogeneous results, no consensus on the underlying mechanisms has been reached. The aim of the present study was to obtain further details of the central perception and processing of the tinnitus signal. Positron emission tomography (PET) was used to map the tinnitus-specific central activity. By contrasting PET-images of suppressed tinnitus with PET-images of the habitual tinnitus sensation, we were able to identify a right prefrontal-temporal network associated with the perception of tinnitus. Besides the evidence of activation of associative auditory sensory regions, the results indicated that activation of cortical centres subserving attention and emotion may underlie the continuous irritability associated with severe tinnitus.


Subject(s)
Attitude to Health , Nerve Net/diagnostic imaging , Nerve Net/metabolism , Perception/physiology , Tinnitus , Tomography, Emission-Computed , Adult , Affect/physiology , Auditory Pathways/metabolism , Brain/diagnostic imaging , Brain/metabolism , Female , Functional Laterality/physiology , Hippocampus/diagnostic imaging , Hippocampus/metabolism , Humans , Male , Middle Aged , Tinnitus/psychology
18.
Audiology ; 39(1): 30-7, 2000.
Article in English | MEDLINE | ID: mdl-10749069

ABSTRACT

We have used positron emission tomography (PET) to test a specific hypothesis of a neural system subserving auditory temporal processing (acoustical stimulus duration discrimination). Maps of the cerebral blood flow distribution during specific stimulations were obtained from five normally-hearing and otherwise healthy subjects. The auditory stimuli consisted of sounds of varying duration and of auditorily presented words in which the duration of the initial phoneme was manipulated. All stimuli alternated with conditions of silence in a subtraction paradigm. The blood flow distribution was mapped with O-15-labelled water. The results demonstrated that stimuli requiring recognizing, memorizing, or attending to specific target sounds during temporal processing generally resulted in significant activation of both frontal lobes and the parietal lobe in the right hemisphere. Based on these results, we hypothesise that a network consisting of anterior and posterior auditory attention and short-term memory sites subserves acoustical stimulus duration perception and analysis (auditory temporal processing).


Subject(s)
Temporal Lobe/blood supply , Tomography, Emission-Computed , Adult , Attention/physiology , Audiometry, Pure-Tone/methods , Auditory Threshold/physiology , Female , Humans , Male , Memory/physiology , Parietal Lobe/blood supply , Parietal Lobe/diagnostic imaging , Prefrontal Cortex/blood supply , Prefrontal Cortex/diagnostic imaging , Reflex/physiology , Stapedius/physiology , Temporal Lobe/diagnostic imaging
19.
Hear Res ; 143(1-2): 139-46, 2000 May.
Article in English | MEDLINE | ID: mdl-10771191

ABSTRACT

To investigate the cortical activities while listening to noise and speech in cochlear implant (CI) users, we compared cerebral blood flow in postlingually deafened CI users with that in normal hearing subjects using positron emission tomography. While noise activation in CI users did not significantly differ from that in normal subjects, hearing speech activated more cortical areas in CI users than in normal subjects. A comparison of speech activation in these two groups revealed higher activation in CI users not only in the temporal cortices but also in Broca's area and its right hemisphere homologue, the supplementary motor area and the anterior cingulate gyrus. In postlingually deafened subjects, the hearing of speech coded by CI may be accompanied by increased activation of both the temporal and frontal cortices.


Subject(s)
Cerebral Cortex/physiology , Cochlear Implants , Speech Perception/physiology , Adult , Brain Mapping , Cerebral Cortex/physiopathology , Deafness/physiopathology , Deafness/therapy , Humans , Male , Noise , Reference Values
20.
Biochem Biophys Res Commun ; 266(2): 371-6, 1999 Dec 20.
Article in English | MEDLINE | ID: mdl-10600510

ABSTRACT

Adeno-associated virus (AAV) capsids are composed of three proteins, VP1, VP2, and VP3. These capsid proteins have a common amino acid sequence, being expressed from different initiation codons on the same open reading frame. Although VP1 is necessary for viral infection, it is not essential for capsid formation. The other capsid proteins, VP2 and VP3, are sufficient for capsid formation, but their functions are poorly understood. To investigate the role(s) of the capsid proteins in capsid formation, we used a baculovirus protein expression system to produce virus-like particles (VLPs). We found that varying the ratios of VP2 and VP3 did not affect VLP formation. Further, their physical properties were equivalent to those of empty wild-type particles. The function of VP3 was studied further by fusing a peptide tag, FLAG, to its N-terminus. This chimeric viral protein, in combination with VP2, could assemble into VLPs, indicating that the chimerism of VP3 did not affect VLP formation. Although the monomeric native form of the FLAG-VP3 chimera could react with anti-FLAG antibody, VLP containing the chimeric VP3 could not, suggesting that the N-terminal region of VP3 is located inside the VLP. These observations indicate that it may be possible to utilize AAV VLP as vectors of a broad range of drugs since fusion of the VP3 N-terminus with defined molecules could impose distinct physical properties onto the internal environment of the VLP.


Subject(s)
Capsid/chemistry , Dependovirus/chemistry , Animals , Baculoviridae , Capsid/genetics , Capsid Proteins , Microscopy, Electron , Oligopeptides , Peptides , Recombinant Fusion Proteins , Spodoptera , Ultracentrifugation
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