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Biomedical subjects

T Kano

Publications and source records attributed to T Kano.

At least 55 records · Page 3Linked to original sources

Citrus viroid Ia is a derivative of citrus bent leaf viroid (CVd-Ib) by partial sequence duplications in the right terminal region.

Nucleotide sequences of group I citrus viroids Ia (CVd-Ia) and citrus bent leaf viroid (CBLVd, formerly designated CVd-Ib) isolated from citrus plants in Japan, the Philippines and China have been determined. Citrus samples in Japan and the Philippines contained CVd-Ia, which consists of 328 nucleotides(nt). Although 10 nt longer than the type CBLVd-225A in Israel they share 94% identity in overall nucleotide sequence. The Philippines sample also contained a 329-nt long CVd-Ia sequence variant, in which one base insertion and three substitutions were observed. A citrus in China contained CBLVd, which consists of 318 nt and shares 98% identity to CBLVd-225A. CVd-Ia was clearly separated from CBLVd by two 5-nt insertions located in upper (5'-AGCUG-3') and the lower (5'-CUUCU-3') strand of the right terminal region (which is also designated T2 domain) in rod-like secondary structure. Since both of the additional 5-nt sequences are similar to the adjacent sequences (5'-AGUUG-3' and 5'-CUUCU-3'), we hypothesize that CVd-Ia is a derivative of CBLVd caused by partial sequence duplications and substitutions taking place in the right terminal region.

Base Sequence↗

Alterations in K+ evoked profiles of neurotransmitter and neuromodulator amino acids after focal ischemia-reperfusion.

Secondary elevations in extracellular amino acids occur during reperfusion after transient cerebral ischemia. The delayed accumulation of excitatory amino acids may contribute to the progressive development of neuronal injury. In this study, we explored the mechanisms that may be involved in this phenomenon. Microdialysis samples from probes located in rabbit cortex were analysed with a chiral amino acid procedure. Concentrations of neurotransmitters (L-Glu, GABA), N-methyl-D-aspartate receptor modulators (D-Ser, Gly), an inhibitory neuromodulator (Tau), the lipid component phosphoethanolamine, and L-Gln, L-Ser and L-Ala were measured. Depolarization via perfusion with potassium was used to assess the status of release/reuptake systems at 2 and 4 h reperfusion after 2 h transient focal ischemia. Background experiments classified potassium evoked responses as calcium dependent or calcium-independent by inclusion of 30 microM omega-conopeptide MVIIC or by inclusion of 20 mM magnesium and ommision of calcium. During ischemia, large elevations of almost all amino acids occurred. During reperfusion, secondary elevations in transmitter amino acids (L-Glu, GABA) and N-methyl-D-aspartate receptor modulators (D-Ser, Gly) occurred. Tau remained slightly elevated whereas the lipid component phosphoethanolamine remained high and stable during reperfusion. Reperfusion significantly potentiated the potassium response for amino acids with calcium-dependent responses (L-Glu and GABA). In contrast, calcium-independent responses (Tau, phosphoethanolamine, L-Gln) were significantly attenuated. Intermediate behavior was observed with Gly, while no potassium responses were observed for D-Ser, L-Ser or L-Ala. These data demonstrate that perturbations in evoked amino acid profiles after ischemia-reperfusion are selective. Reduction of calcium-independent responses implicate a general decline in efficacy of transporter mechanisms that restore transmembrane gradients of ions and transmitters. Decreased efficacy of transporter systems may reduce transmitter reuptake and account for the amplified release of L-Glu and GABA, thus contributing to progressive neural dysfunction after cerebral ischemia.

Animals↗

Effects of nitric oxide synthase gene knockout on neurotransmitter release in vivo.

Nitric oxide serves as a diffusible messenger within the neuronal networks of the brain. Recent studies have suggested that nitric oxide may amplify neurotransmitter release via its ability to diffuse in a retrograde manner from postsynaptic to presynaptic neurons. Two isoforms of nitric oxide synthase may be present in neurons: Type I nitric oxide synthase (neuronal isoform) and Type III nitric oxide synthase (endothelial isoform). In this study, we examined the role of nitric oxide as an amplifier of neurotransmitter release by using K+ and N-methyl-D-aspartate stimulations via microdialysis probes located in cortex, striatum, and hippocampus. We compared responses obtained in wild-type mice versus knockout mice deficient in either neuronal isoform of nitric oxide synthase or endothelial isoform of nitric oxide synthase gene expression. No significant differences in glutamate and GABA release were observed between knockout mice and wild-type mice after K+ stimulations. In contrast, N-methyl-D-aspartate-stimulated glutamate release in cortex was significantly reduced in the neuronal NOS knockout mice, and N-methyl-D-aspartate-stimulated GABA release was significantly reduced in all brain regions of endothelial NOS knockout mice. These data suggest that the two nitric oxide synthase isoforms, most likely due to their specific neuronal localizations, may serve different roles in the modulation of excitatory versus inhibitory neurotransmission in mammalian brain.

Animals↗

YM872, a highly water-soluble AMPA receptor antagonist, preserves the hemodynamic penumbra and reduces brain injury after permanent focal ischemia in rats.

BACKGROUND AND PURPOSE: We recently described an image analysis technique based on the temporal correlation mapping (TCM) of injected contrast agents that can be used to distinguish the hemodynamic core and hemodynamic penumbra after focal ischemia. In this study we used this technique for the first time to investigate the effects of the water-soluble AMPA receptor antagonist YM872 in permanent focal ischemia. METHODS: Fischer 344 rats were subjected to permanent occlusion of the middle cerebral artery. Approximately 30 minutes after ischemia, functional CT images were collected with the use of a dynamic scanning protocol with bolus injections of nonionic contrast agent iohexol (1 mL/kg). TCM analysis defined the distributions of hemodynamic core and hemodynamic penumbra. Cerebral perfusion indices were calculated on the basis of the area under the first-pass transit curves. One hour after ischemia, animals were randomly treated with YM872 (n=8, 20 mg/kg per hour over 4 hours) or normal saline (n=10). Twenty-four hours later, neurological deficits were evaluated, and conventional CT and triphenyltetrazolium chloride staining were used to define volumes of ischemic damage. RESULTS: At 24 hours after ischemia, hypodense lesions were visible on conventional CT scans that were highly correlated with triphenyltetrazolium chloride lesion volumes. YM872 improved neurological deficits and reduced volumes of ischemic damage in cortex (90+/-14 versus 170+/-16 mm3 in controls) but not striatum (57+/-14 versus 79+/-6 mm3 in controls). Comparison of early TCM images with conventional CT scans of ischemic injury showed that the hemodynamic core was always damaged in all rats. In controls, 54% of the tissue within the hemodynamic penumbra evolved into ischemic damage compared with 24% in YM872-treated rats. Furthermore, the perfusion index corresponding to the ischemic damage threshold was significantly reduced by YM872 (28+/-2% versus 37+/-2% in controls). CONCLUSIONS: These results indicate that YM872 is a neuroprotective compound that ameliorates the deterioration of the hemodynamic penumbra after focal ischemia.

Animals↗

Safety management of a patient undergoing thoracic aortic surgery by spinal evoked potential monitoring.

We have presented a patient (48 year-old male) in whom the evoked spinal potential monitor detected impending spinal ischemia after aortic cross-clamping, which allowed surgical intervention to be modified so as to restore the decaying evoked spinal potential. The patient received replacement of the dissecting aneurysm in the thoracic descending aorta with clamping of the aorta at the sites immediately proximal and distal to the aneurysm and initiation of femoro-femoral venoarterial bypass under normothermia. The evoked spinal potential was recorded via the T12/L1 epidural electrode in response to transdural electric stimulation of the spinal cord at the C7/T1 level. As the evoked spinal potential gradually decreased in amplitude without latency prolongation after aortic cross-clamping, the distal clamp was moved from the T6 vertebral level to the T4. The reduced spinal potential then returned to the baseline amplitude. This episode was repeated twice from surgical necessity. The patient was free from any neurological disorders postoperatively.

Aortic Dissection↗

[Comparison of the vascular effects of propofol and those of thiopental in patients under cardiopulmonary bypass].

The effects of propofol (1 mg.kg-1) and thiopental (2.5 mg.kg-1) on the vascular smooth muscle were investigated in 10 cardiac patients on cardiopulmonary total bypass using a constant perfusion flow. Radial mean arterial blood pressure (mAP) decreased to 85 +/- 5% (P < 0.01, vs preinjection) in the post-injection late phase (2-3 min) after propofol, and to 90 +/- 6% (P < 0.01) after thiopental. MAP after thiopental showed a transient initial increase to 115 +/- 8% (P < 0.01) in the post-injection early phase (-1 min). Skin blood flow (SBF) in the middle finger-tip increased to a peak of 450 +/- 120% (P < 0.01) in the post-injection late phase after propofol, and to 240 +/- 60% (P < 0.05) after thiopental. The increase in SBF after propofol was greater than that after thiopental (P < 0.05). The decrease in mAP and the increase in SBF under the constant perfusion flow are considered mainly due to a direct drug action of dilating peripheral vessels. In conclusion, this in vivo human study suggests that propofol (1 mg.kg-1) causes more potent vasodilatation in the peripheral vessels than thiopental (2.5 mg.kg-1).

Aged↗

[201T1C1 accumulation dynamics in glioma with different grades of malignancy: an investigation using dynamic SPECT].

Dynamic SPECT was performed using 201TICI in a total of 21 gliomas, 14 cases of glioblastoma multiforme (GM) and 7 cases of anaplastic astrocytoma (AA), to investigate the relationship between test results and malignancy. The accumulation of isotope (counts/pixel) in the tumor was measured every 3 minutes with dynamic SPECT. The initial 3-minute value was reduced from subsequent accumulations (counts/minute) to obtain the time-activity curve (TAC). Thallium index (TL index), the ratio of 15-minute accumulation in the tumor to that in the same region of the contralateral normal brain, was also calculated. TL index was significantly higher (p < 0.05, Mann-Whitney test) in GM (6.25 +/- 1.97) than in AA (4.10 +/- 1.66), although no clear differential value could be determined between the two. TAC in the GM group showed that compared with the initial 3-minute value, accumulation increased significantly (p < 0.05) at every measurement point after isotope injection: 6 minutes, 0.660 +/- 0.671; 9 minutes, 1.322 +/- 1.319; 12 minutes, 1.315 +/- 1.632 and 15 minutes, 1.234 +/- 1.552. The increase in isotope accumulation in the tumor after 6 minutes or later was noted in 11 of the 14 cases in the GM group. In the AA group, however, there were no significant differences between the initial 3-minute value and value after 6 minutes (-0.283 +/- 0.462), 9 minutes (-0.574 +/- 0.681), 12 minutes (-0.690 +/- 0.611) and 15 minutes (-0.707 +/- 0.636) after isotope injection. A decrease in isotope accumulation in the tumor after 6 minutes or later was noted in 6 of the 7 cases in the AA group. Compared with static SPECT, dynamic SPECT, which can be performed easily and quickly, is more useful in clinical settings because of its high ability to differentiate the grade of malignancy of gliomas.

Adult↗

Low frequency of autoantibodies against Ki-67 antigen in Japanese patients with systemic autoimmune diseases.

The Ki-67 antigen, which is recognized by the monoclonal antibody Ki-67, is a marker of cell proliferation. During cDNA cloning using sera from a patient with systemic lupus erythematosus, we obtained a positive clone encoding part of Ki-67. We determined the frequency of autoantibodies against Ki-67 in patients with systemic autoimmune diseases. Serum samples from 252 patients with rheumatic diseases were examined by immunoblotting with HeLa nuclear extract and the recombinant N-terminus of the Ki-67 antigen. Autoantibodies against Ki-67 antigen were detected in two out of 76 patients with systemic lupus erythematosus and one out of 90 patients with scleroderma. While, in a previous report, anti-Ki-67 antibodies were frequently targeted by a certain strain of autoimmune mice, our results indicated that Ki-67 was a minor target of autoantibodies among Japanese patients with systemic autoimmune diseases.

Autoantigens↗

Clinicohistological study of oligodendroglioma and oligoastrocytoma.

The clinical and histological characteristics of oligodendroglioma and oligoastrocytoma were investigated in patients, mainly adults with supratentorial tumors, who were treated with surgery and radiotherapy, and with chemotherapy for recurrent, anaplastic tumors, or both. The median survival time was 13.2 years for oligodendroglioma (four patients), 12.7 years for anaplastic oligodendroglioma (five patients), 13.5 years for oligoastrocytoma (seven patients), and 4.8 years for anaplastic oligoastrocytoma (four patients). Two of three recurrent oligodendrogliomas and two of two recurrent oligoastrocytomas showed malignant transformation. Minigemistocytes were sometimes recognized in recurrent tumors and had a sinister prognosis. Oligodendroglioma and oligoastrocytoma may transform into each other at recurrence.

Adolescent↗

[Intravenous anesthetics, acting on the gamma-amino butric acid (GABA)A receptor, potentiate the herbal medicine "saiko-keishi-to"-induced chloride current].

We have reported that the Japanese herbal medicine "Saiko-Keishi-To" (SK) which is often used for treating epileptic patients activates the GABAA receptor-mediated chloride current (Icl). In the present study, we examined whether the SK-induced Icl could be potentiated by several intravenous anesthetics known to interact with the GABAA receptor, and also examined whether SK could potentiate the GABA-induced Icl. Whole-cell patch-clamp recordings were made from cultured rat dorsal root ganglion cells. The peak amplitude of the Icl evoked by SK (2 mg.ml-1) increased after pentobarbital (50 microM) to 184 +/- 26% (n = 5), diazepam (1 microM) to 166 +/- 29% (n = 5), and propofol (5 microM) to 294 +/- 93% (n = 5) from their respective controls, while the anesthetics did not activate the Icl by themselves. The peak amplitude of the Icl evoked by GABA (10 microM) increased after propofol (5 microM) to 617 +/- 189% of the control (n = 4), but decreased to 84 +/- 7% of the control by SK (0.2 mg.ml-1, n = 4). These results indicate that the SK-induced Icl can be potentiated by the intravenous anesthetics, positive allosteric modulators of the GABAA receptor-Cl- channel complex and that SK is not a positive allosteric modulator, but a partial agonist for the GABAA receptor. Our study thus suggests that the combined use of SK and anticonvulsants such as barbiturates and benzodiazepines may be more effective in treating epileptic patients than SK alone.

Anesthetics, Intravenous↗

[Effects of human atrial natriuretic peptide on hemodynamics and pulmonary gas exchanges in cardiac surgery patients].

We investigated the effects of human atrial natriuretic peptide (hANP) on hemodynamics and pulmonary gas exchanges in 22 cardiac surgery patients without pulmonary hypertension. In 10 patients, hANP was infused at a rate of 0.2 microgram.kg-1.min-1 throughout the surgery (hANP group), while in other 12 patients hANP was not infused at all (control group). Before cardiopulmonary bypass (CPB), mean arterial pressure and systemic vascular resistance decreased and cardiac output increased significantly in hANP group as compared with those in control group. After weaning from CPB and at the completion of surgery there was no significant difference in these hemodynamic variables between the two groups. Mean pulmonary arterial pressure, pulmonary vascular resistance, arterial pH, arterial oxygen tension, arterial carbon dioxide tension and shunt ratio did not show any significant difference between the two groups throughout surgery. These findings indicate that hANP infusion causes greater systemic vasodilation with less pulmonary vasodilation, and suggest that this systemic vasodilating effect contributes to the improvement of left ventricular function in patients undergoing open heart surgery.

Aged↗

The Japanese herbal medicine 'saiko-keishi-to' activates GABAA receptors of rat sensory neurons in culture.

The mechanism underlying the anticonvulsant action of 'Saiko-Keishi-To' (SK), the Japanese herbal medicine, was examined using whole-cell patch-clamp recording from cultured rat dorsal root ganglion cells. Neurons were held at -60 mV and perfused with an internal solution containing a high concentration of Cl-. Under these circumstances, SK produced an inward current which reversed at +8 mV, and was identical to the gamma-aminobutyric acid (GABA)-induced chloride current (IC). The SK-induced current was completely blocked by bicuculline. SK depressed a high voltage-activated calcium current (HVA-ICa), but this depression could not be antagonized by either phaclofen or saclofen. Of nine crude herbal drugs constituting SK, only Bupleuri radix, Ginseng radix, Zingiberis rhizoma and Paeoniae radix produced the inward currents blocked by bicuculline. These results suggest that SK, and four of its crude herbal drugs, activate the ICl mediated by the GABAA receptor. In addition, SK depresses a HVA-ICa through some mechanism other than an activation of GABAB receptors.

Animals↗

Non-neurogenic periodic fluctuations in heart rate and vasomotion appearing in familial amyloid polyneuropathy (FAP) Type I (Met30).

In order to evaluate the function of the autonomic nervous system, power spectral analysis of heart rate fluctuation and waveform observation of cutaneous vasomotion were conducted in 3 patients with familial amyloid polyneuropathy Type 1 (FAP) (Met30) with autonomic disorders. In 2 FAP patients in the early stage, both high (HFC: 0.12-0.4 Hz) and low frequency components (LFC: 0.04-0.12 Hz) in the heart rate spectrum, and basic (BW) and reflex waves (RW) in the vasomotion were all markedly suppressed. However, in an FAP patient in the advanced stage, prominent spectral peaks were recognized in both the spectral bands of LFC and HFC. HFCs were neither correspondent with the respiratory frequency nor depressed by atropine, and BW was not affected by acute denervation using a local anesthetic. RW was absent irrespective of the denervation. These results suggest that the denervated heart and vascular smooth muscles might have newly acquired periodic fluctuations, although the physiological mechanism and meanings remain to be investigated.

Adult↗

A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3.

A cDNA encoding a novel member of the mitogen-activated protein kinase kinase (MAPKK) family, MAPKK6, was isolated and found to encode a protein of 334 amino acids, with a calculated molecular mass of 37 kDa that is 79% identical to MKK3. MAPKK6 was shown to phosphorylate and specifically activate the p38/MPK2 subgroup of the mitogen-activated protein kinase superfamily and could be demonstrated to be phosphorylated and activated in vitro by TAK1, a recently identified MAPKK kinase. MKK3 was also shown to be a good substrate for TAK1 in vitro. Furthermore, when co-expressed with TAK1 in cells in culture, both MAPKK6 and MKK3 were strongly activated. In addition, co-expression of TAK1 and p38/MPK2 in cells resulted in activation of p38/MPK2. These results indicate the existence of a novel kinase cascade consisting of TAK1, MAPKK6/MKK3, and p38/MPK2.

Amino Acid Sequence↗

Two-Dimensional NMR Study of a Liquid-Crystal Solution under Magic-Angle Spinning. Conformation of Carboxylic Ionophore Lasalocid A Dissolved in a Lyotropic Liquid Crystal

The conformation of a carboxylic ionophore, lasalocid A, has been determined in a lyotropic liquid crystal by means of magic-angle spinning (MAS) and two-dimensional NMR experiments. The information extracted from ROESY spectra measured under MAS was analyzed according to the distance-geometry algorithm. The liquid crystal used for the solvent is cesium perfluorooctanoate dissolved in D2O, and the resulting structure of lasalocid A is a cyclic one, indicating cation complexation within a hydrophobic region of the liquid crystal. In this way, the two-dimensional MAS NMR experiment is proved to be a useful technique in conformational studies of complex molecules dissolved in lyotropic liquid crystal which may be regarded as offering a membrane-like environment.

Journal Article↗

Decreased cerebrospinal fluid levels of substance P in Machado-Joseph disease.

To clarify the mechanism of brain impairment in Machado-Joseph disease (MJD), we measured the cerebrospinal fluid (CSF) levels of substance P in 7 patients (mean age 45.7 +/- 12.09 years) with this disease. Four patients had type I and three had type II disease. Findings were compared with those obtained in 14 age-matched controls, 8 patients with Parkinson's disease, 7 patients with multiple system atrophy, and 6 patients with myopathy. The CSF level of substance P was significantly (p = 0.0000) lower in the patients with MJD, being 44.5% of the control value. However, the mean CSF levels of substance P in the patients with Parkinson's disease, multiple system atrophy, or myopathy did not differ significantly from that in the control subjects. The alteration in the CSF level of substance P may be related to the neurological impairment observed in MJD.

Adult↗