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J Kawakami

Publications and source records attributed to J Kawakami.

At least 19 recordsLinked to original sources
PubMed2005

Relationship between the pharyngeal airway space and craniofacial morphology, taking into account head posture.

This study assessed the relationship between craniofacial characteristics and the size of the pharyngeal airway space (PAS), taking into account head posture. Sixty dental students 25-30 years of age (30 men and 30 women) were examined by lateral cephalometry. The data were corrected with the use of appropriate regression equations for the PAS. The PAS significantly correlated with hyoid position, maxillary and mandibular size, maxillary and mandibular prognathism, and mandibular inclination. A large, anteriorly positioned mandible was associated with a large PAS-TP (the most proximal distance between the posterior pharyngeal wall and the tongue base). Uvula length and PNS-Ba (the distance between the most posterior point of the hard palate and the most inferior point of the anterior foramen magnum) correlated with PAS-UP (the most proximal distance between the posterior pharyngeal wall and uvula). Our results suggest that the anteroposterior dimension of the PAS is substantially affected by the size of the enclosure surrounding the PAS, including the maxilla, mandible and soft palate.

Adult↗
PubMed2005

Computed tomographic analysis of the position and course of the mandibular canal: relevance to the sagittal split ramus osteotomy.

The aim of this study was to investigate the position and course of the mandibular canal through the mandibular ramus using computed tomographic (CT) imaging and to relate the findings to performing sagittal split ramus osteotomies. The mandibles of 35 patients with skeletal Class III prognathism with symmetry (12 males and 23 females) were observed on transaxial computed tomograms acquired with a slice thickness of 2 mm. The position and course of the mandibular canal from the mandibular foramen to the mandibular body at the level of the second molar were measured at four specific locations in the same plane. Among the 70 rami examined, lack of a bone marrow space on the buccal side, including a fusion type anatomy with no buccal side cortical bone of the mandibular canal, were observed at the CT location between the mandibular foramen and mandibular angle. Our results suggest that special care must be taken when sagittal splitting is performed, and the safest location for the buccal corticotomy is anterior to the mandibular angle.

Adolescent↗
PubMed2001

Thermodynamic stability of base pairs between 2-hydroxyadenine and incoming nucleotides as a determinant of nucleotide incorporation specificity during replication.

We investigated the thermodynamic stability of double-stranded DNAs with an oxidative DNA lesion, 2-hydroxyadenine (2-OH-Ade), in two different sequence contexts (5'-GA*C-3' and 5'-TA*A-3', A* represents 2-OH-Ade). When an A*-N pair (N, any nucleotide base) was located in the center of a duplex, the thermodynamic stabilities of the duplexes were similar for all the natural bases except A (N = T, C and G). On the other hand, for the duplexes with the A*-N pair at the end, which mimic the nucleotide incorporation step, the stabilities of the duplexes were dependent on their sequence. The order of stability is T > G > C >> A in the 5'-GA*C-3' sequences and T > A > C > G in the 5'-TA*A-3' sequences. Because T/G/C and T/A are nucleotides incorporated opposite to 2-OH-Ade in the 5'-GA*C-3' and 5'-TA*A-3' sequences, respectively, these results agree with the tendency of mutagenic misincorporation of the nucleotides opposite to 2-OH-Ade in vitro. Thus, the thermodynamic stability of the A*-N base pair may be an important factor for the mutation spectra of 2-OH-Ade.

Base Pairing↗
PubMed2001

Age difference in simultaneous permeation and metabolism of ethyl nicotinate in rat skin.

The age-dependent characteristics of transdermal permeation of ethyl nicotinate (EN) and its metabolism to nicotinic acid (NA) were examined in rats at the ages of a fetus at 21 d, 3, 10, 50, 270 and 360 d. Skin transport in vitro was investigated using mounted skin in side-by-side diffusion chambers, and flux of EN and NA was determined. With developing and aging in rats, EN flux from EN-saturated solution declined gradually, however, NA flux increased drastically at 10 and 50 d. To elucidate the mechanism of this age-dependent escalation of NA flux, a hydrolysis study was performed using skin homogenate, and the Michaelis-Menten parameters (Vmax and Km) of EN were evaluated. Vmax and Vmax/Km ratio showed the same tendency with NA flux/total (EN+NA) flux ratio, suggesting that skin esterases in rats are developed gradually after birth, then increase markedly and become steady in the adult period. On the other hand, the affinity parameter, Km, was almost the same among all ages. Moreover, metabolic saturation of esterase during the transdermal process occurred in all ages, and maximal NA flux and EN concentration in the donor compartment for the maximal NA flux were also affected by age. These findings indicated that the discrepancy in transdermal profiles of EN among the ages tested was dominantly due to the difference in the development of esterase in the growth process.

Aging↗
PubMed2000

In vitro selection of aptamers that act with Zn2+.

An in vitro selection was carried out with Zn2+ to isolate novel RNA molecules, zinc-dependent aptamers, that bind to HIV-1 Tat protein. RNAs bound to Tat were collected by using a nitrocellulose filter from a library of random RNAs and regenerated to the next generation of the RNA library by subsequent reverse transcription, polymerase chain reaction, and transcription. Sequences of the selected RNAs were determined after 6 and 12 rounds of the selection. The control clones after normal selection procedure with Mg2+ had a consensus UUG that resembled essential sequences of TAR or Arg aptamers. On the other hand, many unique sequences were revealed from a library selected with Zn2+ and the RNA with most abundant sequence (clone 31) bound to Tat tightly only when Zn2+ existed. The secondary structure of clone 31 RNA was predicted by using a computational prediction with our thermodynamic parameters and enzymatic scission of the RNA. Several model RNAs were prepared and the binding property of these RNAs to Tat were investigated. As a result, all the model RNAs did not reproduce the binding property of clone 31. Therefore, the Tat aptamer that acts with Zn2+ should require a relatively longer region of the sequence which is able to offer tertiary cooperation of several motifs for the binding.

Base Sequence↗
PubMed2000

Inhibitory effect of azole antifungal agents on the glucuronidation of lorazepam using rabbit liver microsomes in vitro.

Azole antifungal agents (azoles) have inhibitory effects on the cytochrome P450. However, the effect of azoles on conjugative metabolism has not been given much attention. Lorazepam (LZP), a benzodiazepine sedative agent, is known to be metabolized by uridine 5'-diphosphate (UDP)-glucuronyltransferase. Herein we report investigation of the effect of azoles on the enzyme-kinetics of glucuronidation of lorazepam using rabbit liver microsomes in vitro. The Km and Vmax for LZP glucuronidation were determined to be 0.26+/-0.08 mM and 1.25+/-0.21 nmol/min/mg protein, respectively, when evaluated in the presence of a detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) (0.8 mg/mg protein). Azoles fluconazole, miconazole, and ketoconazole competitively inhibited the glucuronidation of LZP, with Ki values of 7.17+/-4.78 mM, 0.17+/-0.08 mM, and 0.092+/-0.026 mM, respectively. These results are comparable to the previously reported Ki values of azoles with zidovudine (AZT) glucuronidation (1.4, 0.18, and 0.08 mM for fluconazole, miconazole, and ketoconazole, respectively) [Sampol et al., Br. J. Clin. Pharmacol., 40, 83-86, 1995]. Therefore, in order to avoid possible side effects of LZP, the concomitant administration of LZP and azoles should be carefully evaluated.

Animals↗
PubMed1999

In vivo and in vitro toxicodynamic analyses of new quinolone-and nonsteroidal anti-inflammatory drug-induced effects on the central nervous system.

We investigated the correlation between an in vivo isobologram based on the concentrations of new quinolones (NQs) in brain tissue and the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) for the occurrence of convulsions in mice and an in vitro isobologram based on the concentrations of both drugs for changes in the gamma-aminobutyric acid (GABA)-induced current response in Xenopus oocytes injected with mRNA from mouse brains in the presence of NQs and/or NSAIDs. After the administration of enoxacin (ENX) in the presence or absence of felbinac (FLB), ketoprofen (KTP), or flurbiprofen (FRP), a synergistic effect was observed in the isobologram based on the threshold concentration in brain tissue between mice with convulsions and those without convulsions. The three NSAIDs did not affect the pharmacokinetic behavior of ENX in the brain. However, the ENX-induced inhibition of the GABA response in the GABAA receptor expressed in Xenopus oocytes was enhanced in the presence of the three NSAIDs. The inhibition ratio profiles of the GABA responses for both drugs were analyzed with a newly developed toxicodynamic model. The inhibitory profiles for ENX in the presence of NSAIDs followed the order KTP (1.2 microM) > FRP (0. 3 microM) > FLB (0.2 microM). These were 50- to 280-fold smaller than those observed in the absence of NSAIDs. The inhibition ratio (0.01 to 0.02) of the GABAA receptor in the presence of both drugs was well-fitted to the isobologram based on threshold concentrations of both drugs in brain tissue between mice with convulsions and those without convulsions, despite the presence of NSAIDs. In mice with convulsions, the inhibitory profiles of the threshold concentrations of both drugs in brain tissue of mice with convulsions and those without convulsions can be predicted quantitatively by using in vitro GABA response data and toxicodynamic model.

Animals↗
PubMed1998

Development and histologic characteristics of synovitis induced by trauma in the rat temporomandibular joint.

Histopathological changes caused by trauma to the rat temporomandibular joint synovium were examined by light microscopy. The trauma was induced by forced hypermobility of the condyle. Pathological changes of the synovium were found primarily in the anterior pouch of the upper joint compartment. The main findings included surface cell proliferation, increased capillary hyperemia, fibrin deposits on the surfaces of inflamed synovial membranes, and fibrinous adhesion between closely opposed synovial membranes. A gradual change from fibrinous adhesion to fibrous adhesion was also seen.

Animals↗
PubMed1998

Histologic study of synovitis induced by trauma to the rat temporomandibular joint.

OBJECTIVE: The purpose of this study was to establish and histologically examine the time course of synovitis induced by trauma to the rat temporomandibular joint. STUDY DESIGN: Synovitis of the temporomandibular joints of 8-week-old male Wister rats was induced by forced condylar hypermobility, which was administered 10 times successively once a day for 10 days. Pathologic changes were observed microscopically at 2 and 5 days and 2, 4, 6, 8, 10, and 20 weeks after treatment. RESULTS: Histologic findings from the 5th day to the 6th week after treatment were characterized by multiple layers of synovial cells, an increase of dilated vasculature, fibrin deposits, and synovial adhesion. These findings were in good agreement with those reported for the human temporomandibular joint. The pathologic changes decreased with advancing time, and synovitis was not observed at 20 weeks after treatment. CONCLUSION: The present procedure for inducing synovitis of the temporomandibular joint in rats will be useful in understanding the pathogenesis of synovitis in human temporomandibular joints.

Animals↗
PubMed1998

Three-dimensional structure of a glycosphingolipid having a novel carbohydrate linkage, Galbeta1-4(Fucalpha1-3)Glcbeta1-3Galbeta, determined by theoretical calculations.

The novel glycosphingolipid, SEGLx (Galbeta1-4(Fucalpha1-3)Glcbeta1-3GalbetaCer), which was identified by us (Kawakami Y, et al. (1993) J Biochem 114: 677-83), shows a characteristic spectrum on 1H-NMR analysis, in which the anomeric proton resonances of a reducing end galactose and a glucose are split. To elucidate the structural characteristics of SEGLx, we determined its three-dimensional (3D) structure by means of computer simulation, involving such techniques as molecular mechanics (MM2), the semiempirical molecular orbital method (AM1), molecular dynamics (Amber), and computer 3D modelling. With the hypothesis that all OH group(s) of a ceramide participate in intramolecular hydrogen bonds, two kinds of stable conformers, horizontal and right-angled ones, were formed, depending on the ceramide species. The present findings suggest that the chemical species of both the long chain base and fatty acid moieties, mainly the occurrence of OH group(s), affect the chemical shifts of the anomeric proton resonances not only of the reducing terminal galactose but also the penultimate glucose through the formation of intramolecular hydrogen bonds. Computer simulation through theoretical calculation and 3D modelling was shown to be the best means of confirming the results obtained by experimental analysis.

Algorithms↗
PubMed1998

Relationship between disc displacement and morphologic features of skeletal Class III malocclusion.

The present study assessed the relationship between disc displacement and facial morphologic features in 48 patients with skeletal Class III malocclusion. Clinical examination, standardized lateral oblique temporomandibular joint radiographs, and cephalographs were used to investigate this relationship. Disc displacement was evaluated by the presence of joint sounds (clicking and crepitation) or restricted condylar translation at maximal mouth opening. Thirty-two patients with signs of disc displacement were compared with 16 patients without signs of disc displacement. Results showed that patients with signs of disc displacement had a significantly larger gonial angle and/or SN-MP of the mandible. Thus, morphologic features of patients with skeletal Class III malocclusion may represent a risk factor for the development of disc displacement.

Adult↗
PubMed1997

Analysis of the cleavage reaction of a trans-acting human hepatitis delta virus ribozyme.

The cleavage reaction catalyzed by the trans -acting genomic ribozyme of human hepatitis delta virus (HDV) was analyzed with a 13mer substrate (R13) and thio-substituted [SR13(Rp) and SR13(Sp)] substrates under single-turnover conditions. The cleavage of RNA by the trans -acting HDV ribozyme proceeded as a first order reaction. The logarithm of the rate of cleavage (kclv) increased linearly (with a slope of approximately 1) between pH 4.0 and 6.0, an indication that a single deprotonation reaction occurred. This result suggests that kclv reflects the rate of the chemical cleavage step, at least around pH 5. The amount of active complex with the SR13(Sp) substrate was almost as large as with R13 (60-80%), whereas the amount of the corresponding active complex formed with the SR13(Rp) substrate was, at most, 20% of this value (with 0.5-100 mM Mg2+ions) at pH 5.0. Nonetheless, the value of kclv for all substrates was almost the same (0.4-0.5 min-1). Neither a 'thio effect' nor a 'Mn2+rescue effect' were observed. These results suggest that Mg2+ions do not interact with pro-R oxygen directly but are essential to the formation of the active complex of the ribozyme and its substrate.

Base Sequence↗
PubMed1997

Inhibitory effect of new quinolones on GABA(A) receptor-mediated response and its potentiation with felbinac in Xenopus oocytes injected with mouse-brain mRNA: correlation with convulsive potency in vivo.

Convulsions induced by the interaction of new quinolone antimicrobial agents (NQs) and nonsteroidal anti-inflammatory drugs (NSAIDs) were previously reported, and blockade of GABA(A) receptor by NQs and its potentiation with NSAIDs were considered as one of its possible mechanisms. However, useful methodology for prediction of convulsive potencies of NQs with or without NSAIDs in vivo based on in vitro screening was not established. Therefore, we applied the Xenopus oocytes translation system of exogenous messenger RNA (mRNA) to examine the mechanism of convulsion induced by interaction of NQs and NSAIDs, and the relationship between convulsive potencies in vivo and inhibitory effect on GABA-induced current response in vitro was investigated. This system also has alternative possibility for the in vivo toxicological studies sacrificing innumerous animals. Glutamic acid, kainic acid, quisqualic acid, NMDA, and serotonin-induced currents were not modified by ENX of NQs and/or FLB of NSAIDs, while glycine- and ACh-induced currents were slightly inhibited. GABA (10 microM)-induced current was inhibited by norfloxacin (NFLX), ciprofloxacin, ENX, and ofloxacin (OFLX) with IC50 of 17, 33, 58, and 280 microM, respectively. IC50 of NQs decreased to 1/3 (OFLX)-1/165 (NFLX) in the presence of 10 microM FLB, while FLB did not modulate the GABA response in the absence of NQs. CSF concentration of ENX at the time of convulsion in clinical situation approximated the IC50 of ENX for the GABA response. The increase of incidence for NQs-induced convulsion by concomitant NSAIDs in vivo could also be explained by the potentiation of inhibitory effects of NQs with FLB in the normal range of CSF concentration of these drugs. We also examined convulsive potency (threshold dose for convulsion) in CNS by intracerebral infusion of NQs to mice with or without FLB pretreatment, and significant correlations between the convulsive potencies and IC50 of NQs for the GABA response were observed. These findings suggested that the blockade of GABA-ersic neurotransmission in CNS is a dominant mechanism of convulsion induced by NQs and that the convulsant-adverse reaction of NQs in vivo may be predicted from the inhibitory effect on the GABA(A) receptor in vitro using the Xenopus oocytes translation system of exogenous mRNA.

Animals↗
PubMed1997

Neurotoxic study of H2 antagonists using Xenopus oocytes injected with mouse-brain mRNA.

To clarify the dominant mechanism for the convulsant activity of H2 antagonists, the effects of an H2 antagonist, cimetidine, on membrane currents induced by various agonists were investigated. In Xenopus oocytes injected with mouse-brain mRNA, acetylcholine (ACh), serotonin (5-HT), gamma-aminobutyric acid (GABA), glycine (Gly), glutamic acid (Glu), kainic acid (KA), quisqualic acid (QA) and N-methyl-D-aspartic acid (NMDA)-induced current responses were recorded under a voltage-clamp condition. Cimetidine inhibited GABA-induced currents in a concentration-dependent manner; however, the current responses induced by the other agonists were not modified. The IC50 of various H2 antagonists, famotidine, nizatidine, cimetidine and ranitidine, for GABA (10 microM)-induced current response were 66, 260, 450 and 980 microM, respectively. However, these values of cimetidine and ranitidine were 40-400 times higher than the reported brain and cerebrospinal fluid (CSF) concentration of H2 antagonists at the occurrence of a clonic convulsion in vivo. In conclusion, we observed an inhibitory effect of H2 antagonists on the GABA response; however, this inhibition of GABA-mediated neurotransmission may not be the dominant mechanism for H2 antagonist-induced clonic convulsion in vivo.

Animals↗
PubMed1997

Effect of acute renal failure on neurotoxicity of enoxacin in rats.

We investigated the effect of acute renal failure on the neurotoxicity of enoxacin (ENX) in rats. Experimental acute renal failure was produced by bilateral ureteral ligation. ENX was intravenously infused to ureter ligated (UL) and control rats, and its concentration in plasma, brain and cerebrospinal fluid (CSF) was compared. Plasma concentration of ENX increased rapidly in UL rats as compared with control rats. Brain/plasma concentration ratio (Kp)-time profile of ENX was similar in UL and control rats. Brain concentration of ENX at the occurrence of convulsion did not depend on the infusion rate, suggesting that in the brain tissue it equilibrates rapidly with the site of action for clonic convulsion. Brain concentration of ENX in UL rats at the occurrence of clonic convulsion was lower than that in control rats. A similar tendency was also observed with CSF concentration. In conclusion, the potentiation of neurotoxicity of ENX with acute renal failure may be caused by not only decreased capability for renal elimination of ENX but also increased sensitivity to convulsant activity of ENX in the central nervous system.

Acute Kidney Injury↗
PubMed1997

Evolution of a phosphorothioate RNA library during in vitro selection.

We carried out an in vitro selection of aptamers from an RNA library with phosphorothioate linkages instead of normal phosphodiesters. This "thio-RNA" library had smaller dissociation rate constant (kd) to a target protein than a natural RNA library. On the basis of the results, an improved selection procedure to obtain ideal nucleic acid drugs will be discussed.

Base Sequence↗
PubMed1996

Constructing an efficient trans-acting genomic HDV ribozyme.

We have engineered a genomic HDV ribozyme to construct several trans-acting ribozymes for use in trans to cleave target RNAs. Among the 10 different combinations attempted, only HDV88-Trans had cleavage activity on the 13-nucleotide substrate, R13, in vitro. To improve the cleavage efficiency, at least in vitro, of the HDV88-Trans ribozyme (kclv = 0.022 min(-1)), we have constructed several variants that differ in forming stem II (length) in the pseudoknot secondary structure model. When cleavage rate constants were analyzed and compared among variants of HDV88-Trans, HDV88-Trans-4 yielded kclv = 1.7 min(-1). HDV88-Trans-4 thus represents the highest active genomic HDV ribozyme that functions in trans thus far constructed, and has activity under physiological conditions (pH 7.1 at 37 degrees C with 1 mM of MgCl2).

Base Sequence↗