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Biomedical subjects

K Hanada

Publications and source records attributed to K Hanada.

At least 73 records · Page 4Linked to original sources
PubMed2000

The relationship between frontal facial morphology and occlusal force in orthodontic patients with temporomandibular disorder.

The aim of this study was to investigate the relation between frontal craniofacial morphology and the distribution of occlusal force in orthodontic patients with and without TMD. Experimental data were obtained from 45 female orthodontic patients (TMD-free group: 22 subjects; TMD group: 23 subjects) using the pressure-sensitive sheet. The following results were obtained: (1) There were significant differences in the gonial angle width and the mandibular deviation of the postero-anterior cephalogram between the two groups. (2) There were significant differences in occlusal force, occlusal contact area and average occlusal pressure between the two groups. (3) On the relation between the frontal craniofacial morphology and the occlusal data, the asymmetry indices of occlusal force and occlusal contact area showed significant positive correlations to the mandibular deviation and the ratios of maxillary and gonial angle widths in the TMD group. The TMD-free group showed the smaller mandibular deviation and the smaller asymmetry indices of occlusal force and occlusal contact area than those in the TMD group. It could be concluded that orthodontic patients with TMD may have not only the morphological disharmony but also the imbalance of occlusal force.

Adolescent↗
PubMed2000

Host cell-derived sphingolipids are required for the intracellular growth of Chlamydia trachomatis.

Chlamydia trachomatis, an important cause of human disease, is an obligate intracellular bacterial pathogen that relies on the eukaryotic host cell for its replication. Recent reports have revealed that the C. trachomatis vacuole receives host-derived sphingolipids by fusing with trans-Golgi network (TGN)derived secretory vesicles. Here, it is shown that these lipids are required for the growth of the bacteria. C. trachomatis was unable to replicate at 39 degrees C in the Chinese hamster ovary (CHO)-derived cell line SPB-1, a cell line incapable of synthesizing sphingolipids at this temperature because of a temperature-sensitive mutation in the serine palmitoyltransferase (SPT) gene. Complementation with the wild-type SPT gene or addition of exogenous cell-permeable sphingolipid precursors to the mutant cells restored their ability to support chlamydial replication. L-cycloserine (L-CS) and fumonisin B1 (FB1), inhibitors of sphingolipid biosynthesis, decreased the proliferation of the bacteria in eukaryotic cells at concentrations that also decreased host cell sphingolipid synthesis. In the case of FB1, the vacuoles appeared aberrant; the addition of sphingolipid precursors was able to reverse the altered morphology of the FB1-treated vacuoles. Collectively, these data strongly suggest that the growth and replication of chlamydiae is dependent on synthesis of sphingolipids by the eukaryotic host cell and may contribute to this organism's obligate intracellular parasitism.

Acyltransferases↗
PubMed2000

Changes in ocular surface caused by antiglaucomatous eyedrops: prospective, randomised study for the comparison of 0.5% timolol v 0. 12% unoprostone.

AIM: To study changes induced in ocular surface epithelia and the tear film by antiglaucomatous eyedrops. A beta blocker (0.5% timolol) and a novel prostaglandin F(2alpha) metabolite related drug (0.12% unoprostone) were examined in a prospective, randomised fashion. METHODS: 40 patients were randomly assigned to use either 0. 5% timolol (timolol group) or 0.12% unoprostone eyedrops (unoprostone group) twice a day for 24 weeks. In addition to routine ocular examinations, corneal epithelial integrity (vital staining tests, tear film break up time (BUT), anterior fluorometry, specular microscopy) and tear function (Schirmer's test, cotton thread test, tear clearance test (TCT)) were examined before and after the treatment. RESULTS: Both eyedrops caused significant reduction in intraocular pressure from the baseline levels. No significant changes were noted in corneal integrity in both groups, except a decrease in BUT at 20 weeks in the timolol group. The timolol group demonstrated significant decreases in Schirmer's test, tear clearance test, and tear function index (Schirmer's test value multiplied by clearance test); however, no such changes were noted in the unoprostone group. CONCLUSION: While unoprostone eyedrops caused no adverse effects on the corneal epithelial integrity and tear function, timolol caused significant impairments in tear production and turnover.

Adrenergic beta-Antagonists↗
PubMed2000

Effect of trimethoprim on the renal clearance of lamivudine in rats.

Lamivudine undergoes minimal metabolism and renal clearance of the unchanged drug is the predominant mechanism of clearance. The effect of trimethoprim on the renal clearance of lamivudine was investigated in rats in-vivo. Total renal clearance of lamivudine was about three times higher than the glomerular filtration rate in rats receiving an infusion of tritium-labelled lamivudine. Concomitant infusion of trimethoprim reduced the renal clearance of lamivudine to about half, but did not affect the level of radioactivity in the renal cortex. When rats received an infusion of lamivudine with probenecid, cimetidine or quinidine, the renal clearance of lamivudine was only significantly reduced by co-administration of cimetidine. These findings suggest that secretion in the renal proximal tubule takes an active part in the total renal clearance of lamivudine, and that cationic drugs such as trimethoprim and cimetidine may inhibit the secretion of lamivudine without greatly affecting the concentration of lamivudine in the renal cortex.

Animals↗
PubMed2000

Effect of lamivudine on uptake of organic cations by rat renal brush-border and basolateral membrane vesicles.

The effect of lamivudine on uptake of a representative organic cation, tetraethylammonium (TEA), by rat renal brush-border membrane vesicles (BBMV) and basolateral membrane vesicles (BLMV) has been investigated. The pH-driven uptake of TEA by BBMV (pHin = 6.0, pHout = 7.5) was inhibited by lamivudine. The IC50 value (concentration resulting in 50% inhibition) for the concentration-dependent effect of lamivudine on TEA uptake by BBMV after 30 s was 2668 microM whereas IC50 values for cimetidine and trimethoprim were < 2.5 microM and < 25 microM, respectively. The early uptake of TEA by BLMV was also reduced significantly by lamivudine. The IC50 value for the concentration-dependent effect of lamivudine on uptake of TEA by BLMV at 30 s was > 25 mM, whereas the IC50 values for cimetidine and trimethoprim were 2116 microM and 445 microM, respectively. These findings suggest that compared with other cationic drugs, such as trimethoprim and cimetidine, lamivudine is a weak inhibitor of organic cation transport into the tubules by the brush-border and basolateral membranes of renal epithelial cells. It is unlikely lamivudine will have any significant effect on the excretion of co-administered cationic drugs by the renal tubules.

Animals↗
PubMed2000

Pharmacokinetics and toxicodynamics of cisplatin and its metabolites in rats: relationship between renal handling and nephrotoxicity of cisplatin.

The renal handling of cisplatin and its metabolites and the relationship between the pharmacokinetics of these platinum species in the kidney and nephrotoxicity in rats were studied by carrying out pharmacokinetic-pharmacodynamic analysis. Rats received cisplatin intravenously as a bolus (2-10 mgkg(-1)) or by constant infusion (55 and 140 microg min(-1) kg(-1)). After intravenous administration of each platinum species, the platinum concentrations of unchanged cisplatin and its mobile and fixed metabolites were determined separately. Nephrotoxicity was estimated by measuring the blood urea nitrogen (BUN) levels and the sigmoid Emax model was used to determine the relationship between pharmacokinetic parameters and BUN levels 5 days after cisplatin administration. Cisplatin and its mobile metabolites in plasma distributed more rapidly and extensively into the kidney (mean apparent kidney-to-plasma concentration ratios were 2.69 and 7.12 mL (g tissue)(-1), respectively) than into the liver (less than 1 mL (g tissue)(-1)). Concomitant administration of mobile metabolites did not significantly alter the disposition of cisplatin. Nephrotoxicity, estimated by measuring BUN levels, appeared to be related to the plasma concentration of intact cisplatin, not total platinum, because mobile metabolites formed from cisplatin showed little nephrotoxicity. The sigmoid Emax model showed the maximum BUN level reached after cisplatin administration was related to the area under the renal cisplatin concentration-time curve (AUCk).

Animals↗
PubMed2000

Effect of buthionine sulphoximine, glutathione and methimazole on the renal disposition of cisplatin and on cisplatin-induced nephrotoxicity in rats: pharmacokinetic-toxicodynamic analysis.

The aim of this study was to classify the protective mechanisms of DL-buthionine-(S,-R)-sulphoximine, glutathione and methimazole on cisplatin-induced nephrotoxicity in rats. An Emax model was used to study the effect of these compounds on the pharmacokinetics of cisplatin, especially renal handling and intra-renal biotransformation. Cisplatin (5 mg kg(-1)) was administered as an intravenous bolus to rats treated with either 0.9% NaCl (control), buthionine sulphoximine, glutathione or methimazole. The blood urea nitrogen level was monitored to estimate cisplatin-induced nephrotoxicity. To estimate renal handling of cisplatin, cisplatin was infused intravenously to rats treated with 0.9% NaCl, buthionine sulphoximine, glutathione or methimazole. The concentrations of unchanged cisplatin in plasma, urine and kidney were determined by a post-column derivatization HPLC method. The relationship between the pharmacokinetics and toxicodynamics of cisplatin was analysed using a sigmoid Emax model. All compounds studied ameliorated significantly the nephrotoxicity of cisplatin. The renal accumulation of cisplatin was reduced significantly by pretreatment with buthionine sulphoximine but not by either glutathione or methimazole. Although glutathione treatment did not affect the renal accumulation of cisplatin, it significantly decreased the binding of cisplatin to the intrarenal organelle and the decreased binding was well correlated to the decrease of the blood urea nitrogen level. In summary, pharmacokinetic-toxicodynamic analysis will be useful for classifying the protective mechanism of cisplatin-induced nephrotoxicity.

Animals↗
PubMed2000

Telomerase activity and p53 expression in pterygia.

PURPOSE: To investigate tolomerase activity and p53 expression in pterygial tissue. METHODS: Pterygia tissue was obtained during excisional surgery fr om 35 eyes of 35 patients, and superior bulbar conjunctival tissue from the same eye was also sampled as control when possible. Fluorescence telomeric repeat amplification protocol was used to measure telomerase activity in whole pterygium samples from 9 cases and in the epithelium and stroma of pterygium from another 10 cases. p53 protein content was measured by enzyme-linked immunosorbent assay (ELISA) in tissues obtained from 7 eyes, as well as in epithelial cell suspensions collected by brush cytology in 8 eyes. Six samples were also analyzed for UV-specific mutations in the p53 gene by the single-strand conformation polymorphism technique and DNA sequencing. A conjunctival epithelial cell line was irradiated with sublethal levels of UV-B to investigate whether telomerase activity can be induced in vitro. RESULTS: In all, 63% of pterygia samples demonstrated telomerase activity, whereas all 10 paired conjunctival control samples were negative (P = 0.05, chi-square test). Of the 10 samples in which telomerase activity was measured separately in the epithelium and stroma of pterygia, 5 samples were positive in the epithelium, only 1 of which had activity in the stroma. Average telomerase activity in positive samples was 18.44 +/- 8.77 U/microg protein, compared with telomerase activity measured in a carcinoma in situ patient (33.73 U/microg), and in an immortalized conjunctival epithelial cell line (50.72 +/- 15.55 U/microg). Telomerase activity was not upregulated in this cell line by UV-B exposure. All 6 pterygia samples tested for p53 mutations did not reveal the UV-specific mutations in exons 5, 6, 7, or 8. No statistical significance was observed in the pterygium or conjunctiva p53 protein levels in epithelial cells collected by brush cytology, while p53 protein level was lower in pterygia when measured in whole tissue samples. CONCLUSIONS: Telomerase activity was detected in some pterygia, mostly in the epithelium. Pterygia was not associated with an increase in epithelial p53 protein content measured by ELISA.

Cell Line↗
PubMed1999

Genetic evidence for ATP-dependent endoplasmic reticulum-to-Golgi apparatus trafficking of ceramide for sphingomyelin synthesis in Chinese hamster ovary cells.

LY-A strain is a Chinese hamster ovary cell mutant resistant to sphingomyelin (SM)-directed cytolysin and has a defect in de novo SM synthesis. Metabolic labeling experiments with radioactive serine, sphingosine, and choline showed that LY-A cells were defective in synthesis of SM from these precursors, but not syntheses of ceramide (Cer), glycosphingolipids, or phosphatidylcholine, indicating a specific defect in the conversion of Cer to SM in LY-A cells. In vitro experiments showed that the specific defect of SM formation in LY-A cells was not due to alterations in enzymatic activities responsible for SM synthesis or degradation. When cells were treated with brefeldin A, which causes fusion of the Golgi apparatus with the endoplasmic reticulum (ER), de novo SM synthesis in LY-A cells was restored to the wild-type level. Pulse-chase experiments with a fluorescent Cer analogue, N-(4,4-difluoro-5,7-dimethyl-4-bora-3a, 4a-diaza-s-indacene-3-pentanoyl)-D-erythro-sphingosine (C5-DMB-Cer), revealed that in wild-type cells C5-DMB-Cer was redistributed from intracellular membranes to the Golgi apparatus in an intracellular ATP-dependent manner, and that LY-A cells were defective in the energy-dependent redistribution of C5-DMB-Cer. Under ATP-depleted conditions, conversion of C5-DMB-Cer to C5-DMB-SM and of [3H]sphingosine to [3H]SM in wild-type cells decreased to the levels in LY-A cells, which were not affected by ATP depletion. ER-to-Golgi apparatus trafficking of glycosylphosphatidylinositol-anchored or membrane-spanning proteins in LY-A cells appeared to be normal. These results indicate that the predominant pathway of ER-to-Golgi apparatus trafficking of Cer for de novo SM synthesis is ATP dependent and that this pathway is almost completely impaired in LY-A cells. In addition, the specific defect of SM synthesis in LY-A cells suggests different pathways of Cer transport for glycosphingolipids versus SM synthesis.

Adenosine Triphosphate↗
PubMed1999

Effects of morphine on the distribution of Fos protein in the trigeminal subnucleus caudalis neurons during experimental tooth movement of the rat molar.

The present study was undertaken to disclose temporal changes in the distribution of Fos-like immunoreactive (-IR) neurons in the trigeminal subnucleus caudalis (SpVc), one of the important relay nuclei for processing the nociceptive information from the oro-facial regions, following induction of experimental tooth movement in rat upper molars. Furthermore, the effect of morphine and naloxone on the levels of Fos-IR neurons in the SpVc was examined. The experimental tooth movement was induced by insertion of an elastic rubber between the first and second upper molars. In normal animals, Fos-IR neurons were rarely observed in the SpVc. Immediately after insertion of the elastic band, the distribution of Fos-IR neurons was comparable to that observed in normal animals. The number of Fos-IR neurons increased significantly from 1 to 4 h following the induction of experimental tooth movement, reaching a maximum at 2 h, and then decreasing gradually. Most of the neurons were localized in the dorsomedial portion of the superficial layers of the ipsilateral SpVc near the obex, but a few were observed at the ventral portion of the SpVc. The neurons at the superficial layers and ventral portion of the contralateral SpVc also showed Fos-like immunoreactivity, but their numbers were significantly smaller than those on the ipsilateral side. Pretreatment with morphine (3 and 10 mg/kg, i.p.) significantly reduced the induction of Fos-IR neurons at the superficial layers of the ipsilateral SpVc in a dose-dependent manner, and its effect was antagonized by the subsequent treatment of naloxone (2 mg/kg, i.p.). Naloxone pretreatment enhanced the expression of Fos-IR neurons on the ipsilateral SpVc. The present results of a reduction of Fos-IR neurons by morphine pretreatment suggest that the induction of Fos-IR neurons may be due to the noxious stimulation caused by induction of experimental tooth movement.

Analgesics, Opioid↗
PubMed1999

Manganese intoxication during total parenteral nutrition: report of two cases and review of the literature.

We report two cases of manganese (Mn) intoxication during total parenteral nutrition including manganese (Mn). Both patients showed parkinsonism with psychiatric symptoms and elevated serum Mn levels. T1-weighted magnetic resonance images (MRI) revealed symmetrical high intensity lesions in the globus pallidus. Discontinuation of Mn supplementation and levodopa treatment improved the symptoms and MRI abnormalities in the both patients. Thus, careful attention should be paid to the long-term intravenous administration of Mn.

Aged↗
PubMed1999

Cellular kinetics and gene mutations in gallbladder mucosa with an anomalous junction of pancreaticobiliary duct.

Anomalous junction of the pancreaticobiliary duct (AJPBD) is thought to be an important risk factor for gallbladder carcinoma in Japan. We have reported the characteristic pathology, cellular kinetics, and gene mutations to clarify the mechanism of carcinogenesis in gallbladder mucosa with AJPBD. A comprehensive review of the literature was undertaken, with referencing of major articles on the subject. A sequence of hyperplastic changes, with a corresponding increase in cellular kinetics with progression through dysplasia to carcinoma is important in carcinogenesis of gallbladder mucosa with AJPBD. p53 mutations may contribute to the transition from premalignancy to malignancy in the early stage of carcinogenesis of the gallbladder mucosa, regardless of the presence of AJPBD. The specific mutation of GGT-to-GAT in codon 12 of K-ras may play an important role in carcinogenesis of gallbladder mucosa with AJPBD.

Adenocarcinoma↗
PubMed1999

Adult onset limb-girdle type mitochondrial myopathy with a mitochondrial DNA np8291 A-to-G substitution.

We analyzed mitochondrial DNA (mtDNA) from 7 patients in four families with adult onset limb-girdle type mitochondrial myopathy to clarify their genetic background. The patients, 2 men and 5 women, showed common clinical features, characterized by isolated skeletal myopathy, high serum creatine kinase level, ragged-red fibers and cytochrome c oxidase-defective fibers. Analysis of muscle biopsy specimens indicated that cytochrome c oxidase activity was decreased relative to that of citrate synthase in 5 of the 7 patients. Southern blotting and direct sequence analyses showed an A-to-G homoplasmic transition at np8291 and intergenic COII/tRNA (Lys) 9bp deletion in all patients. This substitution was detected in only 2 of 600 control individuals including healthy subjects and patients with other neuromuscular disorders; these 2 individuals had diabetes mellitus and myotonic dystrophy, respectively. Consequently, the mtDNA transition at np8291 was a rare polymorphism. However, the 7 patients we studied had identical clinical, pathological, biochemical, and genetic features. Therefore, limb-girdle type mitochondrial myopathy with this rare polymorphism may form a subgroup of adult onset mitochondrial myopathy.

Adult↗
PubMed1999

Effects of disopyramide and verapamil on renal disposition and nephrotoxicity of cisplatin in rats.

PURPOSE: The purpose of this study was to determine the effects of disopyramide and verapamil on the renal handling of cisplatin (CDDP) and nephrotoxicity in rats. The stereoselective effect of verapamil was also studied. METHODS: CDDP was administered to rats by i.v. bolus injection or by infusion at a constant rate with or without concomitant administration of racemic disopyramide, racemic verapamil, or each verapamil enantiomer. The concentrations of CDDP in plasma and in the kidney and liver were determined by HPLC. In separate experiments, CDDP was administered as described above, and blood urea nitrogen (BUN) was monitored for 7 days. RESULTS: The BUN level after administration of CDDP was significantly reduced by coadministration of either disopyramide or verapamil. Renal accumulation of CDDP was significantly reduced by these drugs, whereas accumulation into the liver was not significantly changed. The relationship between the BUN levels and the area under the curve of CDDP concentration in the kidney versus time (AUCk) was analyzed using a sigmoid Emax model; this showed that the reduced BUN levels were explained by the AUCk. Furthermore, verapamil showed stereoselective inhibition of the renal accumulation of CDDP. CONCLUSIONS: The renal accumulation of CDDP was inhibited by disopyramide and verapamil, and this inhibition resulted in the amelioration of nephrotoxicity.

Animals↗
PubMed1999

In vivo gene introduction into keratinocytes using jet injection.

Successful keratinocyte gene therapy requires the development of efficient methods of gene transfer to keratinocytes. Jet injection of a solution containing DNA can be used to transfer genes to several tissues in vivo. In this article, we tried to introduce DNA into rat and human keratinocytes using this method. First, we fired a beta-gal expression vector into rat skin at several distances using a jet injector and examined beta-gal activity in the epidermal keratinocytes. The highest activity in keratinocytes was found when the plasmid was fired at 10 cm from the skin surface; the activity lessened as the firing distance became shorter than 10 cm. Next, we transplanted human skin on to a nude rat, fired the vector into the human skin from a distance of 10 cm and examined the beta-gal activity. We also injected the same amount of plasmid with a needle to compare jet with needle injections. The results showed that jet injection of the naked DNA could introduce and express DNA in human keratinocytes in vivo and that jet injection exhibited much higher activity than needle injection. Jet injection of the naked DNA will provide a method for keratinocyte gene therapy in the future.

Animals↗
PubMed1999

A multiparametric analysis of occlusal and periodontal jaw reflex characteristics in adult skeletal mandibular protrusion before and after orthognathic surgery.

Periodontal jaw reflex, duration of percussion sounds, tooth mobility, and time-moment analysis of occlusal contacts by the T-scan system were recorded in seven pre-orthognathic surgery patients and six post-orthognathic surgery patients over a 2-year period. The results showed that: (i) reflex response to the pressure applied to the upper right central incisor in the lingolabial direction varied, depending on the background jaw-clenching force (BCF) of the same-sided first molar. The BCF level required to elicit excitatory reflexes was only 0 kgf, and inhibitory reflexes were clearly elicited with a BCF of 1 kgf and beyond before orthognathic surgery. After orthognathic surgery BCF levels required to elicit excitatory reflexes were 0-4 kgf, and inhibitory reflexes were elicited with a BCF of 6 kgf and above; (ii) duration of percussion sounds determined via an occlusal sound analyser decreased in both the upper right central incisor and upper right first molar while tooth mobility measured by 'Periotest(R)' increased in the upper right central incisor, but did not change in the same-sided first molar after orthognathic surgery; (iii) the time moments of occlusal contacts were symmetrical toward the midsagittal axis of the occlusal plane after orthognathic surgery. The centre of the anterioposterior occlusal contacts did not differ between pre- and post-orthognathic surgery groups.

Adolescent↗