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Biomedical subjects

F Kato

Publications and source records attributed to F Kato.

At least 19 recordsLinked to original sources
PubMed2001

Reduction by sevoflurane of adenosine 5'-triphosphate-activated inward current of locus coeruleus neurons in pontine slices of rats.

Increasing evidence indicates that volatile general anesthetics exert their effects by affecting various types of membrane conductance expressed in the central nervous system (CNS), such as ligand-gated receptor-channels. The most recently identified family of the receptor-channels in the CNS are the extracellular ATP-gated channels (P2X purinoceptors). In the present study, we tested whether volatile anesthetics can affect P2X receptor function in the CNS network. We recorded whole-cell currents of locus coeruleus (LC) neurons in pontine slices from young rats. Adenosine 5'-triphosphate (ATP) sodium (0.03-3 mM) evoked a rapidly rising and moderately desensitizing inward current (50-200 pA) in a dose-dependent manner in LC neurons at a holding potential of -80 mV. Perfusion with clinically relevant concentration of sevoflurane (0.1-0.5 mM) reduced the ATP-induced inward current in a dose-dependent manner (to 56.8+/-5.9% of control with 0.5 mM sevoflurane; mean+/-S.E.M., n=13). Estimated IC(50) of sevoflurane was 0.59 mM. We conclude that the attenuation of extracellular ATP-mediated signaling in the central nervous system might be one of the multiple actions of volatile anesthetics.

Adenosine Triphosphate↗
PubMed2001

Distinct modulation of evoked and spontaneous EPSCs by purinoceptors in the nucleus tractus solitarii of the rat.

Whole-cell transmembrane currents of second-order neurones in the caudal part of the nucleus tractus solitarii (cNTS) of brainstem slices of the rat were recorded to analyse the effects of adenosine 5'-triphosphate (ATP) on: (1) EPSCs evoked by the solitary tract stimulation (eEPSCs) and (2) spontaneous EPSCs (sEPSCs). ATP (10-6 to 10-4 m) significantly reduced the amplitude of eEPSCs to 46.6 +/- 7.4 % and increased the frequency of sEPSCs to 268.0 +/- 71.5 % of the control without significant changes in sEPSC amplitude. These opposite effects of ATP on eEPSCs and sEPSCs were concurrently observed in about 80 % of cNTS neurones recorded. The reduction of eEPSC amplitude by ATP was similarly observed with the addition of an equimolar solution of adenosine but not with alpha,beta-methylene ATP and was suppressed by 8-cyclopentyltheophylline (CPT) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Addition of pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) did not affect the reduction of eEPSC amplitude by ATP. The increase in sEPSC frequency by ATP remained under tetrodotoxin addition but was abolished in the presence of PPADS. It is suggested that ATP activates: (1) presynaptic adenosine A1 receptors, after being hydrolysed to adenosine, reducing evoked release of glutamate from the primary afferent terminals and (2) presynaptic P2X receptors on the axon terminals of intrinsic excitatory cNTS neurones facilitating spontaneous release of glutamate. This is the first evidence that ATP modulates excitatory synaptic inputs arising from distinct origins and converging on a single postsynaptic neurone in diametrically opposite directions through activation of distinct presynaptic purinoceptors.

Adenosine Triphosphate↗
PubMed2001

Specific inhibitor of puromycin-sensitive aminopeptidase with a homophthalimide skeleton: identification of the target molecule and a structure-activity relationship study.

2-(2,6-Diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (2: PIQ-22) was found to be a potent and specific inhibitor of puromycin-sensitive aminopeptidase (PSA). Lineweaver-Burk plot analysis showed that PSA is inhibited by PIQ-22 in a non-competitive manner. Structure -activity relationship studies indicated that tautomerism of the imidobenzoylketone group in the cyclic imide moiety of the PIQ-22 skeleton is important for the inhibitory activity.

Aminopeptidases↗
PubMed2001

Determination of indomethacin polymorphic contents by chemometric near-infrared spectroscopy and conventional powder X-ray diffractometry.

A chemoinfometric method for the quantitative determination of the crystal content of indomethacin (IMC) polymorphs, based on Fourier-transform near-infrared (FT-NIR) spectroscopy, was established. A direct comparison of the data with those collected using the conventional powder X-ray diffraction method was performed. Pure alpha and gamma forms of IMC were prepared using published methods. Powder X-ray diffraction profiles and NIR spectra were recorded for six kinds of standard material with various contents of the gamma form of IMC. Principal component regression (PCR) analyses were performed on the basis of the normalized NIR spectral sets of standard samples with known contents of the gamma form of IMC. A calibration equation was determined to minimize the root mean square error of the prediction. The predicted gamma form contents were reproducible and had a relatively small standard deviation. The values of the gamma form contents predicted by the two methods were in close agreement. The results indicated that NIR spectroscopy provides an accurate quantitative analysis of crystallinity in polymorphs compared with the results obtained by conventional powder X-ray diffractometry.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Threshold effect for teratogenic risk of radiation depends on dose-rate and p53-dependent apoptosis.

PURPOSE: To obtain evidence that the p53 gene is indispensable for reduction of high teratogenic risk of radiation at a high dose-rate to zero risk by lowering the dose-rate. MATERIALS AND METHODS: Wild-type p53(+/+), heterozygous p53(+/-) and null p53(-/-) mice were exposed to gamma-rays at high or low dose-rates during days 9.5-10.5 of gestation. The incidence of malformations and prenatal deaths was studied. Frequencies of cells dying by apoptosis were measured during or after protracted irradiation. RESULTS: After irradiation with 2 Gy, the frequency of apoptotic cells increased to 20% for p53(+/+) mice and did not increase at all for p53(-/-) mice. For p53(+/+) mice, 2 Gy y-rays induced 70% malformations when given at 1.06 Gy/min, but no malformations above the control when given at 1.2 mGy/min. In contrast, after irradiation of p53(-/-) foetuses with 2 Gy at 1.2mGy/min, the incidence of malformations increased 12% above control levels. CONCLUSION: Foetal irradiation with 2 Gy at 1.2 mGy/min was not teratogenic for p53(+/+) mice but teratogenic for p53(-/-) mice. This indicates that the p53 gene is indispensable for a threshold effect in the risk of radiation at low doses or dose-rates.

Animals↗
PubMed2000

Synergistic bactericidal effects of acrinol and tetracycline against Pseudomonas aeruginosa.

Combined treatment of acrinol (Ac) and tetracycline hydrochloride (Tc) against Pseudomonas aeruginosa strains isolated from clinical specimens synergistically increased the bactericidal effect. The minimum bactericidal concentration (MBC) of Ac against P. aeruginosa strain no. 985 was 200 microg/ml, while the MBC of Ac against strains no. 47 and no. 783 was above 800 microg/ml for each. The MBC of Tc was above 400 microg/ml against each of the tested strains. However, simultaneous treatment with 25 microg/ml Ac and 200 microg/ml Tc against P. aeruginosa strain no. 985 decreased the viable cell number from 107 cfu/ml to <10 cfu/ml within 24 h, while a higher concentration of Tc (400 microg/ml) with Ac (25 microg/ml) reduced the viable cell number to <10 cfu/ml within 8 h. A similar synergistic bactericidal effect of Ac and Tc was observed in strains no. 47 and no. 783 by treatment with 200 microg/ml Ac and 200 microg/ml or 400 microg/ml Tc. The degree of bactericidal effect against P. aeruginosa was proportional to the concentration of Tc under the condition of a constant concentration of Ac. Furthermore, Ac-treated cells of strain no. 47 were killed by a following Tc treatment, but cells pretreated with Tc did not show such a sensitivity to Ac. To induce the synergistic effect of Ac and Tc, Ac must be applied to P. aeruginosa before or at the same time as Tc.

Anti-Bacterial Agents↗
PubMed2000

Soybean-milk-coagulating activity of Bacillus pumilus derives from a serine proteinase.

A proteolytic enzyme from Bacillus pumilus strain TYO-67, which was able to coagulate the protein in soybean milk, was characterized enzymologically. The optimum pH and temperature for its activities were 9.0 and 50 degrees C, respectively. The enzyme was strongly believed to be a serine proteinase because it was completely inhibited by the addition of diisopropyl fluorophosphate or phenylmethanesulfonyl fluoride. Hammerstein milk casein, cytochrome c and soybean protein were good substrates for the enzyme. Seven cleavages were detected using the oxidized insulin B-chain as peptide substrate for the proteolytic specificity test of the serine proteinase from B. pumilus. The bonds most susceptible to the action of the serine proteinase from B. pumilus were Leu-15-Tyr-16. The mode of action on soybean milk protein by the enzyme from B. pumilus was also investigated. The acidic subunit in glycinin and the alpha-, alpha- and beta-subunits in beta-conglycinin were degraded during the enzyme reaction. However, the basic subunit in glycinin could not be degraded by the enzyme. The formation of coagula in soybean milk caused by the serine proteinase from B. pumilus was mainly due to the hydrophobic interaction.

Bacillus↗
PubMed2000

Assembly, target-signaling and intracellular transport of tyrosinase gene family proteins in the initial stage of melanosome biogenesis.

Assembly, target-signaling and transport of tyrosinase gene family proteins at the initial stage of melanosome biogenesis are reviewed based on our own discoveries. Melanosome biogenesis involves four stages of maturation with distinct morphological and biochemical characteristics that reflect distinct processes of the biosynthesis of structural and enzymatic proteins, subsequent structural organization and melanin deposition occurring in these particular cellular compartments. The melanosomes share many common biological properties with the lysosomes. The stage I melanosomes appear to be linked to the late endosomes. Most of melanosomal proteins are glycoproteins that should be folded or assembled correctly in the ER through interaction with calnexin, a chaperone associated with melanogenesis. These melanosomal glycoproteins are then accumulated in the trans Golgi network (TGN) and transported to the melanosomal compartment. During the formation of transport vesicles, coat proteins assemble on the cytoplasmic face of TGN to select their cargos by interacting directly or indirectly with melanosomal glycoproteins to be transported. Adapter protein-3 (AP-3) is important for intracellular transport of tyrosinase gene family proteins from TGN to melanosomes. Tyrosinase gene family proteins possess a di-leucine motif in their cytoplasmic tail, to which AP-3 appears to bind. Thus, the initial cascade of melanosome biogenesis is regulated by several factors including: 1) glycosylation of tyrosinase gene family proteins and their correct folding and assembly within ER and Golgi, and 2) supply of specific signals necessary for intracellular transport of these glycoproteins by vesicles from Golgi to melanosomes.

Amino Acid Sequence↗
PubMed2000

Comparative evaluation of the degree of indomethacin crystallinity by chemoinfometrical Fourier-transformed [corrected] near-infrared spectroscopy and conventional powder X-ray diffractometry.

A chemoinfometrical method for evaluating the degree of crystallinity based on Fourier-transformed [corrected] near-infrared (FT-NIR) spectroscopy was established and compared with the conventional powder X-ray diffraction method. Powder X-ray diffraction profiles and FT-NIR spectra were recorded for 11 kinds of standard materials with various degrees of crystallinity obtained by physically mixing crystalline and amorphous indomethacin (IMC). Chemoinfometric analysis was performed on the FT-NIR spectral data sets by multiple linear regression (MLR) (MLR-Set-Up Search program). The crystalline and amorphous forms showed significant NIR spectral peaks. MLR analysis was performed based on normalized NIR spectra sets for standard samples of known crystallinity. A calibration equation was determined to minimize the root mean square error of prediction. The predicted crystallinity values were reproducible and had a smaller standard deviation. The values of crystallinity predicted by X-ray powder diffractometry and FT-NIR spectrometry suggested a satisfactory correlation between the 2 techniques. The results indicated that FT-NIR spectroscopy provides for an accurate quantitative analysis of crystallinity compared with conventional X-ray diffractometry.

Calorimetry, Differential Scanning↗
PubMed2000

Acute inferior myocardial infarction and coronary spasm in a patient with an anomalous origin of the right coronary artery from the left sinus of valsalva.

A 56-year-old Japanese woman with an acute inferior myocardial infarction was admitted to hospital. Emergency coronary angiography revealed an anomalous origin of the right coronary artery from the left sinus of Valsalva, but there was no stenosis or thrombus in either the right or left coronary artery. Coronary spasm was provoked at the site of the proximal portion of the anomalous coronary artery, which was located between the aorta and pulmonary trunk. This was thought to be the cause of the myocardial infarction.

Acetylcholine↗
PubMed1999

Inspiration-promoting vagal reflex under NMDA receptor blockade in anaesthetized rabbits.

1. This study describes a novel vagal respiratory reflex in anaesthetized rabbits. In contrast to the well-known inspiratory (I) off-switching by vagal afferent excitation, this vagal reflex initiates and maintains the central I activity of phrenic nerve discharges in rabbits pre-treated with antagonists of N-methyl-D-aspartate-type excitatory amino acid receptors (NMDA-Rs). 2. Under NMDA-R blockade with either dizocilpine (0.025-0.3 mg kg-1), D-2-amino-5-phosphonopentanoic acid (AP5, 0.5-1 mg, i.c.v.) or ketamine (10 mg kg-1), vagal stimulation at low frequencies (5-40 Hz) during the I phase prevented or markedly delayed the spontaneous I termination. In contrast, stimulation of the same vagal afferent at the same intensity but at a higher frequency (100-160 Hz) during the I phase immediately terminated the I phase. 3. In non-vagotomized rabbits, maintaining the tidal volume at end-expiratory levels during the I phase prevented spontaneous I termination and maintained apneusis after NMDA-R blockade with dizocilpine. 4. Brief stimulation of vagal afferents at low frequency (5-40 Hz) during the expiratory (E) phase constantly initiated phrenic I discharge after NMDA-R block. 5. We conclude that low-frequency discharge of vagal pulmonary stretch receptor afferents, as when lung volume is near functional residual capacity, promotes central I activity under NMDA-R blockade.

Anesthesia↗
PubMed1999

Nonpeptide small-molecular inhibitors of dipeptidyl peptidase IV: N-phenylphthalimide analogs.

A novel series of nonpeptide small-molecular dipeptidyl peptidase IV (DPP-IV) inhibitors with an N-phenylphthalimide skeleton has been developed. Some of the compounds, including 4-amino-(2,6-dimethylphenyl)phthalimides (7), 4- and 5-hydroxy-(2,6-diethylphenyl)phthalimide (11 and 14), 4-hydroxy-(2,6-diisopropylphenyl)phthalimide (12), and thiocarbonyl analogs of (2,6-diisopropylphenyl)phthalimide and their 4,5,6,7-tetrafluorinated derivative (18, 19 and 20), were more potent than the well-known DPP-IV-specific inhibitor, Pro-boroPro (PBP). Among them, 18 was revealed to be a DPP-IV-specific inhibitor, while the others also showed inhibitory activity toward another peptidase, aminopeptidase N (APN).

Cell Line↗
PubMed1999

Preparation and properties of novel gramicidin S analogs possessing a tri-, tetra- or pentamethylene bridge between ornithine side chains.

Gramicidin S (GS) analogs in which the Ndelta atoms of the two Orn side chains are linked by an oligomethylene bridge [-(CH2)n-; n=3-5] were prepared via the bis(p-nitrobenzenesulfonyl) derivative [Orn(NBS)2,2']GS. For comparison the nonbridged secondary amino group-containing analog [Orn(Me)2,2']GS was also prepared. 1H NMR and CD spectral analysis indicated that these analogs adopt the same beta-sheet conformation as GS. The antimicrobial activities of these analogs were very similar, but were slightly dependent on the bridge chain length, the trimethylene-bridged analog being the most potent.

Anti-Bacterial Agents↗
PubMed1999

Pilocarpine-induced cholinergic sweat secretion compared with emotional sweat secretion in atopic dermatitis.

We studied pilocarpine-induced cholinergic sweating, emotional sweating and sympathetic reflex sweating in atopic dermatitis (AD) patients. Secreted sweat was measured both with equipment that continuously records sweat rate and with a filter paper method that measures sweat weight absorbed. Comparison of the two methods revealed that the filter paper method underestimated the sweat secretion in AD patients. While AD patients showed no significant abnormalities in emotional sweating and sympathetic reflex sweating, the duration of pilocarpine-induced sweating was prolonged. The time from the maximal sweat rate until the sweat rate fell to half of the maximal rate was significantly longer in AD patients than in control subjects. In contrast, the time from the beginning of sweat secretion until the maximal sweat rate was not significantly different between AD patients and control subjects. There was no significant difference between AD patients and control subjects in sweat volume secreted in 20 min after pilocarpine iontophoresis. In AD patients, the total sweat volume secreted after pilocarpine iontophoresis was greater than in control subjects, although not significantly. These results suggest that the system of deactivation of pilocarpine-induced sweat secretion is impaired in AD patients whereas the activation system is not altered.

Adult↗
PubMed1999

Structure-function relationship of model Aib-containing peptides as ion transfer intermembrane templates.

Peptaibols comprise a family of peptide antibiotics with high contents of 2-aminoisobutyric acid (Aib) residues and C-terminal amino alcohols. These peptides form alpha-helical structures leading to voltage-gated ion channels in lipid membranes. In the present study, amphiphilic helical Aib-containing peptides of various chain-lengths, Ac-(Aib-Lys-Aib-Ala)n-NH2 (n = 1-5), were designed to investigate the mechanisms of the aggregation and transmembrane orientation of helical motifs in lipid bilayer membranes. Peptide synthesis was performed by the conventional stepwise Fmoc solid-phase method. The crude peptides were obtained in high yields (66-85%) with high purities (69-95%). Conformational analysis of the synthetic peptides was performed by CD spectroscopy. It was found that these peptides take on highly helical structures, and the helicity of the peptides increases with an increase in chain-length. The longest peptide, Ac-(Aib-Lys-Aib-Ala)5-NH2, self-aggregates and adopts a barrel-stave conformation in liposomes. Ac-(Aib-Lys-Aib-Ala)5-NH2 exhibited potent antimicrobial activity against Gram-positive bacteria. Patch-clamp measurements revealed that this peptide can form well-defined ion channels with a long lifetime at relatively low transbilayer potentials and peptide concentrations. For this peptide, the single-channel conductance of the most frequent event is 227 pS, which could be related to a single-state tetrameric pore.

Amino Acid Sequence↗
PubMed1999

Potent homophthalimide-type inhibitors of B16F10/L5 mouse melanoma cell invasion.

Recently, we developed a series of novel and potent aminopeptidase inhibitors with a homophthalimide skeleton. Among them, N-(2,6-diethylphenyl)homophthalimide (PIQ-22) possesses a specific aminopeptidase-inhibiting activity more potent than that of bestatin or actinonin, as assayed in terms of hydrolysis of L-alanine 4-methylcoumaryl-7-amide (Ala-AMC) by human acute lymphoblastic leukemia MOLT-4 cells. We show here that PIQ-22 and its 2,6-dimethylphenyl derivative (PIQ-11) are more potent inhibitors of tumor cell invasion than bestatin and actinonin in a Matrigel assay using mouse melanoma B16F10/L5 cells.

Aminopeptidases↗