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Biomedical subjects

M Senda

Publications and source records attributed to M Senda.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of single and repeated administration of 1,2,3,4-tetrahydroisoquinoline analogs on the binding of [11C]raclopride to dopamine D2 receptors in the mouse brain.

We investigated the effects of intraperitoneal injection of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogs and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the binding of [11C]raclopride to striatal dopamine D2 receptors in mice. The binding of [11C]raclopride, but not of [11C]N-methylspiperone or [11C]nemonapride with higher affinity, to the receptors was significantly decreased immediately after TIQ injection. Neither a dopamine transporter blocker induced such effect nor TIQ affected the dopamine transporter-radioligand binding. Among the compounds investigated, including parkinsonism-inducing TIQ and (R/S)-1-benzyl-TIQ, parkinsonism-preventing (R)- and (S)-1-methyl-TIQ, and probable N-methylated metabolites of TIQ and 1-methyl-TIQ, TIQ and (S)-1-methyl-TIQ had the strongest effect on the binding of [11C]raclopride, and N-methylated derivatives showed less of an effect than the respective parent compounds. The decrease in the binding of [11C]raclopride continued for 7 hours and was followed by an increase until 10 days after the single and subchronic administration of TIQ. These findings suggest that TIQ analogs profoundly stimulated dopamine release which resulted in the competitive inhibition of the binding of [11C]raclopride to dopamine D2 receptors, but did not induce degeneration of the receptors.

Animals↗
PubMed2001

Selective measurement of digital nerve conduction velocity.

We developed a new method to measure the nerve conduction velocity of a single digital nerve. In 27 volunteers (27 hands), we separately stimulated each digital nerve on the radial and ulnar sides of the middle and ring fingers. A double-peaked potential was recorded above the median nerve at the wrist joint when either the radial-side nerve or the ulnar-side nerve of the middle finger was stimulated. The first peak of this potential had disappeared after the digital nerve was blocked under the stimulating electrodes, and the peak appeared again coinciding with the decrease of anesthesia. Shifting the stimulating electrodes on the digital nerve resulted in no significant difference in the peak conduction velocity. It is possible that each peak of the potential was attributable to conduction of an action potential along one of the two digital nerves. This new method allows the assessment of a single digital nerve, and may be clinically useful for assessing the rupture of a digital nerve and the sensory nerve action potentials in carpal tunnel syndrome.

Action Potentials↗
PubMed2001

Synthesis and preliminary evaluation of a carbon-11-labeled adenosine transporter blocker [(11)C]KF21562 .

We prepared an (11)C-labeled adenosine transporter blocker, [1-methyl-(11)C]-3-[1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H, 3H)-quinazolinedione ([(11)C]KF21652) and examined its potential as a positron emission tomography (PET) ligand for mapping adenosine transporters in the brain and peripheral organs. The log P(7.4) value of KF21652 was 3.14, and the K(i) value was 13 nM for adenosine transporters using [(3)H]nitrobenzylthioinosine as a radioligand. In mice, the highest initial uptake was found in the liver, followed by the kidney and small intestine. The brain uptake was very low. The radioactivity level slightly increased with time in the liver and small intestine, but decreased in the other organs. Coinjection of carrier KF21652 slightly decreased the uptake of [(11)C]KF21562 only in the liver, but not in any other organs. Ex vivo autoradiography of the rat brain showed that [(11)C]KF21652 was scarcely incorporated into the brain. On the other hand, in vitro autoradiography showed the binding of [(11)C]KF21562 to adenosine transporters with high nonspecific binding. These results show that the compound is not a suitable PET ligand for mapping adenosine transporters.

Adenosine↗
PubMed2001

Age-related changes of glutathione content, glucose transport and metabolism, and mitochondrial electron transfer function in mouse brain.

To evaluate the oxidative stress-related parameters and to determine their order of appearance in the brain aging process, radionuclide experiments were carried out on male DBF1 mice at 3, 12, 24 and 30 months of age. The content of nonprotein sulfhydryl compounds, mainly glutathione, was estimated with technetium-99m meso-hexamethyl propyleneamine oxime ([99mTc]meso-HMPAO) tissue sampling. Glucose transport and metabolism was examined with [1-14C]2-deoxy-D-glucose (2-DG) tissue sampling. Mitochondrial electron transport function was estimated with [15O]O2 gas-tissue ARG. [99mTc]Meso-HMPAO uptake in brain expressed as standardized uptake value (SUV), (radioactivity in brain tissue/tissue weight)/(total administered radioactivity/body weight), reached maximum at 12 months of age and decreased at 24 and 30 months of age in every region examined. The pattern of 2-DG, expressed as SUV, showed a tendency to increase rather than decrease with aging. [15O]O2 fixation in brain slices remained constant until 24 months, while it decreased significantly at 30 months of age. The results suggested the possibility of using imaging techniques in vivo for longitudinal evaluation of the aging process and indicated reduction of nonprotein sulfhydryl compounds including GSH at the early stages of aging may also accelerate the dysfunction of mitochondrial electron transport and neurodegeneration.

Aging↗
PubMed2001

[11C]Raclopride binding was reduced in vivo by sigma(1) receptor ligand SA4503 in the mouse brain, while [11C]SA4503 binding was not by raclopride.

[11C]Raclopride is widely used as a representative dopamine D(2)-like receptor ligand in positron emission tomography (PET) studies, and [11C]1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride ([11C]SA4503) is a recently developed selective ligand for mapping sigma(1) receptors in the brain. The striatal uptake of [11C]raclopride in mice was reduced by co-injection of an excess amount of SA4503, in spite of the fact that raclopride had no effect on the brain uptake of [11C]SA4503 as shown in a previous study. The blocking effect of SA4503 on the striatal uptake of [11C]raclopride was dose-dependent, but disappeared by 1 h or 6 h after intraperitoneal injection of SA4503. The brain uptake of [11C]SA4503 was not affected by a dopamine transporter inhibitor GBR 12909, nor was [11C]beta-CIT-FP inhibited by SA4503. The IC(50) values of raclopride for sigma(1) and sigma(2) receptor subtypes measured in vitro were 11800 nM and 4950 nM, respectively, suggesting that the affinity was too low for [11C]raclopride to bind in vivo to sigma receptors. On the other hand, the IC(50) value of SA4503 for dopamine D(2) receptors was 470 nM, that is approximate 1/25 of the affinity of raclopride for the dopamine D(2) receptors. Therefore, possible explanations for the partial blocking effects of SA4503 on the striatal uptake of [11C]raclopride are: (1) an excess amount of SA4503 may reduce the [11C]raclopride uptake due to its low affinity for dopamine D(2) receptors, or (2) SA4503 may enhance endogenous dopamine release, which results in the competitive inhibition of the [11C]raclopride uptake. These findings support that both [11C]raclopride and [11C]SA4503 are selective in vivo ligands for dopamine D(2)-like receptors and sigma(1) receptors, respectively, in spite of the partial blocking effect of SA4503 on the striatal uptake of [11C]raclopride.

Animals↗
PubMed2001

Evaluation of neurotoxicity of TIQ and MPTP and of parkinsonism-preventing effect of 1-MeTIQ by in vivo measurement of pre-synaptic dopamine transporters and post-synaptic dopamine D(2) receptors in the mouse striatum.

Parkinsonism-inducing neurotoxicity of 1,2,3,4-tetrahydroisoquinoline (TIQ), as contrasted to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and parkinsonism-preventing effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ) have been investigated in mice by measuring their effects on the in vivo binding of radioligand to pre-synaptic dopamine transporters (DATs) or to dopamine D(2) receptors (D2R) in the striatum. A significant reduction of the ligand-DATs binding was found in the mice treated with MPTP, but not with TIQ, under the dosage inducing behavioral abnormality and loss of tyrosine hydroxylase-positive cells in the substantia nigra. A slight decrease in the ligand-DATs binding was observed in the mice given a larger dose of TIQ. Compensatory up-regulation in the post-synaptic D2Rs was found in the MPTP-treated mice. Pre-treatment with (S)-enantiomer, but not (R)-enantiomer, of 1-MeTIQ prevented the degeneration of DATs to some extent. We concluded that the TIQ-induced parkinsonism model is different from the MPTP-induced model as evaluated by the radioligand-DATs binding and that (S)-1-MeTIQ has a preventing effect for the degeneration of the DATs to a certain extent.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Discordance between cerebral oxygen and glucose metabolism, and hemodynamics in a mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode patient.

A patient with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode (MELAS) syndrome underwent serial measurement of cerebral blood flow with xenon computed tomography (Xe-CBF) while presenting with strokelike episodes accompanied by a cerebral lesion. He underwent positron emission tomography (PET) measurement of the regional cerebral blood flow (PET-CBF), metabolic rate of oxygen (CMRO2), and glucose (CMRGlu) after his symptoms and lesion disappeared. During the symptomatic period, Xe-CBF and the Xe-CBF response to acetazolamide loading were well preserved both in and outside the low-density lesion. In the PET study, decreased CMRO2 and increased PET-CBF and CMRGlu were noted in the entire brain. The strokelike episodes of patients with MELAS are more likely attributed to the failure of oxygen metabolism than to a vascular accident.

Acetazolamide↗
PubMed2001

[Clinical study of 33 children with systemic pneumococcal infections].

We retrospectively analyzed 33 cases of children with systemic pneumococcal infections, 22 bacteremia and 11 meningitis, diagnosed and treated in Asahi General Hospital between 1985 and 1999. The median age at diagnosis was 15 months old and the incidence peaked in infants between 7 and 24 months of age (57.6%). Two cases showed low serum IgG2 levels. Fever was a common symptom in all cases and 13 (39.4%) presented convulsions. Meningitis [median age: 10 months] tended to occur, if not significant, in younger children than bacteremia [16 months]. All cases of meningitis were diagnosed 12 hours or later after the onset of fever, though 54.5% of the cases of bacteremia were diagnosed within 12 hours. The cases of meningitis showed statistically lower white blood cell counts [median: 9,700/mm3] and higher CRP levels [median: 25.6 mg/dl] than those of bacteremia [23,900/mm3 and 4.2 mg/dl, respectively] at diagnosis. Although all cases of bacteremia were cured without any sequelae by antibiotic treatment, 3 cases (27.3%) of meningitis died and 4 (36.4%) developed severe neurological sequelae. Our findings suggest that the putative pathogenesis by which pneumococcal meningitis results from bacteremia and, taking in the account of the poor outcome of meningitis, may justify the early antibiotic intervention against pneumococcal bacteremia.

Bacteremia↗
PubMed2001

Ion-transfer voltammetry of local anesthetics at an organic solvent/water interface and pharmacological activity vs. ion partition coefficient relationship.

The ion-transfer reaction of local anesthetics at an organic solvent/water interface has been studied using cyclic voltammetry (CV) with a stationary nitrobenzene (NB)/water (W) interface. Procaine and seven other local anesthetics gave reversible or quasi-reversible voltammograms at the NB/W interface in the pH range between 0.9 and 9.6. These drugs are present in aqueous solution in either neutral or ionic form, or both forms. The half-wave potential, as determined by the midpoint potential in CV, vs. pH curves, were determined and analyzed to determine the partition coefficients of both neutral and ionic forms of the drugs between NB and W. The partition coefficients of the ionic forms were derived from their formal potential of transfer at an NB/W interface. The dissociation constants of ionic forms of the drugs in NB were also deduced. A high correlation between the pharmacological activity and the partition coefficient of the ionic form of amide-linked local anesthetics has been shown.

Algorithms↗
PubMed2001

[A case of septic shock and disseminated intravascular coagulation following transrectal prostatic biopsy].

A 60-year-old man underwent transrectal six sextant ultrasound-guided prostatic biopsy because of gradual elevation of PSA. Despite postoperative use of amikacin, spiking fever developed the next day and after emergency admission (39 hours after the biopsy), his blood pressure decreased to 56/40 mmHg with WBC 800/mm3, platelets 6.9 x 10(4)/mm3 (decreased further to 0.4 x 10(4)/mm3 on the following day) and FDP 51 micrograms/dl. Intensive care including chemotherapy with broad-spectrum antibiotics and endotoxin removal therapy using a polymyxin B immobilized fiber column (PMX), was useful to recover the patient from septic shock and disseminated intravascular coagulation. As the number of systematic prostatic biopsy is increasing rapidly in Japan, more attention must be paid to potential hazards of this procedure.

Biopsy↗
PubMed2001

Time course changes of nerve conduction velocity in idiopathic carpal tunnel syndrome after endoscopic surgery.

A total of 49 patients (71 hands) underwent endoscopic carpal tunnel release according to the method of Okutsu accompanied by electrophysiological studies performed for idiopathic carpal tunnel syndrome at our department between August 1993 and May 1998. Among them, 41 patients (55 hands) who were followed-up for 12 months or more postoperatively were studied. The clinical outcome was favorable in 50 out of 55 hands (90.9%). In the 5 hands showing poor surgical results, distal motor latency or sensory nerve conduction velocity was not recordable before surgery and had not improved at 1 month postoperatively. In the present study, it is highly likely that the long-term prognosis will be poor when distal motor latency or sensory nerve conduction velocity is not recordable at 1 month after surgery as well as preoperatively. It is possible to identify patients with a poor outcome by performing electrophysiological studies at 1 month after surgery.

Adult↗
PubMed2001

[Quantitative estimation of brain atrophy and function with PET and MRI two-dimensional projection images].

PURPOSE: The purpose of this paper is to estimate the extent of atrophy and the decline in brain function objectively and quantitatively. METHODS: Two-dimensional (2D) projection images of three-dimensional (3D) transaxial images of positron emission tomography (PET) and magnetic resonance imaging (MRI) were made by means of the Mollweide method which keeps the area of the brain surface. A correlation image was generated between 2D projection images of MRI and cerebral blood flow (CBF) or 18F-fluorodeoxyglucose (FDG) PET images and the sulcus was extracted from the correlation image clustered by K-means method. Furthermore, the extent of atrophy was evaluated from the extracted sulcus on 2D-projection MRI and the cerebral cortical function such as blood flow or glucose metabolic rate was assessed in the cortex excluding sulcus on 2D-projection PET image, and then the relationship between the cerebral atrophy and function was evaluated. This method was applied to the two groups, the young and the aged normal subjects, and the relationship between the age and the rate of atrophy or the cerebral blood flow was investigated. This method was also applied to FDG-PET and MRI studies in the normal controls and in patients with corticobasal degeneration. RESULTS: The mean rate of atrophy in the aged group was found to be higher than that in the young. The mean value and the variance of the cerebral blood flow for the young are greater than those of the aged. The sulci were similarly extracted using either CBF or FDG PET images. CONCLUSIONS: The purposed method using 2-D projection images of MRI and PET is clinically useful for quantitative assessment of atrophic change and functional disorder of cerebral cortex.

Adult↗
PubMed2000

Enhanced motor cortical excitability in the unaffected hemisphere after hemispherectomy.

We evaluated motor cortical excitability of the unaffected hemisphere in three patients with intractable epilepsy who underwent hemispherectomy, using transcranial magnetic stimulation (TMS) and PET. TMS of the unaffected hemisphere evoked motor responses not only in the contralateral muscles but also in the ipsilateral ones in all the patients. A PET study in one patient showed activation of the unaffected motor cortex by movement of either arm. All of these responses were enhanced after the hemispherectomy, probably due to motor cortical disinhibition by transection of the corpus callosum. The PET study also showed postoperative activation of the premotor area of the unaffected hemisphere. These phenomena indicate posthemispherectomy neuroplastic reorganization leading to preservation of the motor function after the operation.

Adult↗
PubMed2000

Application of PET-MRI registration techniques to cat brain imaging.

UNLABELLED: In positron emission tomography (PET) studies of diseased animals, it is very useful to have accurate anatomical information as a reference. In human studies, anatomical information is usually obtained from magnetic resonance imaging (MRI) of the subject with retrospective registration of the subject's PET image to the MRI. A number of PET-MRI registration techniques are used for this purpose. However, the utility of these methods has not been tested for animals image registration. This paper studies the feasibility of applying two currently used human brain PET-MRI registration techniques to cat brain images. METHODS: Three cats were anesthetized with isoflurane gas, and PET images were acquired with H(2)(15)O, benzodiazepine receptor ligand 11C-flumazemil (FMZ), dopamine receptor ligand 11C-nemonapride (NEM) and fluorodeoxy glucose (18F-FDG). The four PET scans were acquired consecutively within the same day while the cat remained fixed in the scanner. We also obtained T1-weighted and T2-weighted MRI of the cats in a 4.7 T unit. The PET images were registered to MRI using two human brain registration techniques: a semi-automatic method (SAM), which is a two-step method based on the extraction of the midsagittal plane, and an automatic method (AMIR) method that minimizes PET pixel variance within spatially connected segments determined by MRI. RESULTS: T2-weighted MRI provided better structural information than T1 MRI. FMZ did, while FDG or H(2)O PET images did not, provide a structural outline of the brain. The FMZ PET image was registered to MRI satisfactorily using SAM. The striatum visualized in nemonapride PET image re-sliced with the same parameters matched the striatum identified in T2-weighted MRI. Registration by AMIR was successful by inspection for FMZ, FDG or H(2)O PET images in only one of the three cats. The registration error of SAM was estimated to be less than 2 mm or 2 degrees. CONCLUSION: A satisfactory registration of FMZ-PET to T2-weighted MRI of the cat brain was obtained by a two-step manual registration technique. This will enhance the usefulness of PET in the field of cerebral pathophysiology.

Animals↗
PubMed2000

In vivo imaging of adenovirus-mediated over-expression of dopamine D2 receptors in rat striatum by positron emission tomography.

PET was used to provide in vivo imaging of the over-expression of dopamine D2 receptor (D2R) induced by adenovirus vector-mediated gene transfer in rat striatum. The uptake of three kinds of D2R-specific ligands, [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone, measured by PET was higher in the striatum injected with the vectors for D2R than the contralateral striatum injected with a control vector 2-3 days after injection. However, the uptake of [11C]SCH 23390, a dopamine D1 receptor specific ligand, or [11C]beta-CIT-FP, a dopamine transporter specific tracer, was not different between bilateral striata. Co-injection of excess unlabeled raclopride inhibited the uptake of [11C]raclopride. At day 16 the increased uptake of [11C]raclopride declined to basal level, consistent with past in vitro assessment of this vector. In vivo imaging of D2R will permit longitudinal assessment of the efficiency of this and similar vectors in rat brain that can be related to functional changes being observed.

Adenoviridae↗
PubMed2000

Optical rotation per refractive index unit, or enantiomeric (e) factor, for screening enantioselective catalysts through asymmetric activation or carbohydrates.

A super high-throughput screening (SHTS) system can be constructed by combining high-performance liquid chromatography (HPLC), optical rotation (OR), and refractive index unit (RIU) to determine not only the enantioselectivity of the addition of diethylzinc to an aliphatic aldehyde catalyzed by a binaphthol-zinc complex through asymmetric activation with chiral Schiff bases, but also the enantiopurity of a carbohydrate. The enantiomeric (e) factor, which we define here as optical rotation per refractive index unit, is linearly related to the percent enantiomeric excess (%ee) and is independent of concentration.

Acetonitriles↗
PubMed2000

Intrasubject correlation between static scan and distribution volume images for [11C]flumazenil PET.

Accumulation of [11C]flumazenil (FMZ) reflects central nervous system benzodiazepine receptor (BZR). We searched for the optimal time for a static PET scan with FMZ as semi-quantitative imaging of BZR distribution. In 10 normal subjects, a dynamic series of decay-corrected PET scans was performed for 60 minutes, and the arterial blood was sampled during the scan to measure radioactivity and labeled metabolites. We generated 13 kinds of "static scan" images from the dynamic scan in each subject, and analyzed the pixel correlation for these images versus distribution volume (DV) images. We also analyzed the time for the [11C]FMZ in plasma and tissue to reach the equilibrium. The intra-subject pixel correlation demonstrated that the "static scan" images for the period centering around 30 minutes post-injection had the strongest linear correlation with the DV image. The ratio of radioactivity in the cortex to that in the plasma reached a peak at 40 minutes after injection. Considering the physical decay and patient burden, we conclude that the decay corrected static scan for [11C]FMZ PET as semi-quantitative imaging of BZR distribution is to be optimally acquired from 20 to 40 minutes after injection.

Adult↗