Biomedical subjects

K Okimoto

Publications and source records attributed to K Okimoto.

At least 19 recordsLinked to original sources

PubMed2006

Transgenic rescue from embryonic lethality and renal carcinogenesis in the Nihon rat model by introduction of a wild-type Bhd gene.

We recently reported that a germline insertion of a single nucleotide in the rat homologue of the human Birt-Hogg-Dubé gene (BHD) gives rise to dominantly inherited cancer in the Nihon rat model. In this study, we constructed transgenic Nihon rats with introduction of a wild-type Bhd gene to ascertain whether suppression of the Nihon phenotype is possible. Rescue from embryonic lethality of mutant homozygotes (Nihon/Nihon) and suppression of renal carcinogenesis in heterozygotes (Nihon/+) were both observed, defining the germline Bhd mutation in the Nihon rat as an embryonal lethal and tumor predisposing mutation. This transgenic rescue system will be useful to analyse Bhd gene function, its relation to tumorigenesis in vivo, and genetic-environmental interactions in carcinogenesis.

Animals↗

PubMed2004

Nodular thyroid hyperplasia in a cynomolgus monkey.

Nodular thyroid hyperplasia was found in a 4-year-old male cynomolgus monkey (Macaca fascicularis). The monkey was clinically normal; however, necropsy revealed multiple variably sized nodules in both lobes of the thyroid gland. In contrast to the fairly uniform diameter of the lumen of follicles in the surrounding gland, the diameter of the follicular lumen within the hyperplastic nodules was highly variable and ranged from nonexistent to cystlike. Occasionally, in the larger follicles there were papillary infoldings of epithelium. The hyperplastic nodules were partially encapsulated by a fibrous capsule and showed little compression of the surrounding tissue. The follicular cells and colloid comprising the hyperplastic nodule were immunohistochemically positively stained with the antibody for thyroglobulin. Ultrastructurally, the cells forming follicles had numerous microvilli along the luminal surface, and lysosomal bodies and dilated rough endoplasmic reticulum in the cytoplasm. All these morphologic findings are consistent with nodular thyroid hyperplasia, which is rare in nonhuman primates.

Animals↗

PubMed2001

A novel renal carcinoma predisposing gene of the Nihon rat maps on chromosome 10.

A novel rat model of hereditary renal cell carcinoma (RC) was found in a rat colony of the Sprague-Dawley (SD) strain in Japan, and named the "Nihon" rat in 2000. This study was designed to map the RC susceptibility gene in the Nihon rat using 113 backcross animals. Our present data clearly show that the Nihon gene is genetically linked to interleukin-3 (IL3) gene (chi(2) = 93.6, Lod score = 25.16), lethal (2) giant larvae (LLGL1) locus (chi(2) = 109.0, Lod score = 31.56) and myosin heavy chain, embryonic skeletal muscle (MYHSE) gene (chi(2) = 90.6, Lod score = 23.87), which are located on the distal part of rat chromosome 10. The order of the genes is the Eker (Tsc2) gene (located on the proximal part of rat chromosome 10; human chromosome 16p 13.3)--21.3 cM--IL3 gene (human 5q23-31)--4.4 cM--Nihon gene--0.9 cM--LLGL1 locus (human 17p11.2)--4.4 cM--MYHSE gene (human 17p13.1). We also detected loss of the wild-type allele at the MYHSE locus, fitting Knudson's "two hit" model. Thus, the Nihon rat should have a mutation of a novel tumor suppressor gene related to renal carcinogenesis.

Animals↗

PubMed2000

X-ray crystallographic characterization of nilvadipine monohydrate and its phase transition behavior.

Crystals of nilvadipine monohydrate were obtained from aqueous acetonitrile solution and characterized by powder and single crystal X-ray crystallography and thermal analysis. Water molecules of crystallization exist in nilvadipine monohydrate crystals in a molar ratio of 1:1 (drug-to-water) and were fixed by three hydrogen bonds with two carbonyl groups of the methyl and isopropyl esters, respectively, and one imino group of neighboring nilvadipine molecules. The conformation of the methyl and isopropyl esters in the monohydrate crystal was the reversal of that in the anhydrate crystal due to the presence of hydrogen bonds with water in the former crystal. The monohydrate crystal was slowly converted to the dehydrate at low humidity, and the latter rapidly converted to the former at high humidity. Powder X-ray diffraction studies indicated that the dehydrate retains the original structure of the monohydrate, i.e., a layer structure stacked on the ac plane perpendicular to the b-axis The solubility of the monohydrate in water was lower than that of the dehydrate and anhydrate forms, although the initial dissolution rate of the monohydrate was faster than that of the anhydrate. The present results indicated that the conformation of 1, 4-dihydropyridine-type calcium channel antagonists such as nilvadipine is easily changed by hydrogen bonds with water molecules of crystallization, and the water molecules are mobile through the void spaces formed between the layers in crystals.

Calcium Channel Blockers↗

PubMed2000

Study on masticatory movement and its ability: efficacy of a test capsule in the evaluation of masticatory movement.

It has been shown that a test capsule originally designed as a simple and reliable aid to evaluate masticatory ability could help to identify the characteristics of chewing loops between individuals in evaluation of masticatory movement, and detect even a slight disorder in the stomatognathic system. In this study, the Sirognathograph(R) Analysing System was used to record and analyse mandibular movement with the test capsule and seven foods. In terms of total examination of the chewing rhythm, the test capsule showed a higher SX/SY ratio of chewing cycle duration (SX: variance between individuals, SY: variance between chewing loops of each person) than those of the comparative foods, excluding chewing gum. The coefficient of variation of the test capsule in the dimensions of the chewing path was lower than those of the comparative foods. Reverse and crossover patterns in chewing gum have been frequently observed in subjects with craniomandibular disorders. Subjects with a low frequency of such patterns in chewing gum tended to have a low frequency with the test capsule as well. Those with a high frequency in chewing gum tended to show such patterns with the test capsule more frequently.

Adult↗

PubMed2000

A novel "Nihon" rat model of a Mendelian dominantly inherited renal cell carcinoma.

A novel rat model of hereditary renal cell carcinoma (RC) was found in a rat colony of the Sprague-Dawley strain in Japan, and named the rising "Nihon" rat. In this strain, RCs develop from early preneoplastic lesions, which begin to appear at 4 weeks of age, forming adenomas by the age of 16 weeks. The RCs are predominantly of clear cell type. Southern blot, northern blot and SSCP analyses revealed no change in the Tsc1, Tsc2, VHL, and c-Met genes. Thus, the Nihon rat should be a valuable experimental model for understanding renal carcinogenesis, especially clear cell type, which is common among human RCs.

Animals↗

PubMed2000

Choriocarcinoma and teratoma in the ovary of a cynomolgus monkey.

An ovarian choriocarcinoma was found in a 13-year-old cynomolgus monkey (Macaca fascicularis). The tumor was accompanied by a mature teratoma in the contralateral ovary. Histologically, the choriocarcinoma was characterized by nests of cells where cytotrophoblasts occupied the periphery with syncytiotrophoblasts at the center. Immunohistochemical staining for anti-human chorionic gonadotropin was positive in the syncytiotrophoblasts. The teratoma consisted of well-differentiated epidermal cells, sebaceous glands, hair follicles, cartilage, bone, and teeth. Choriocarcinoma metastases were in multiple organs. The concomitant development of choriocarcinoma and teratoma in the ovary is a consistent finding with the human counterparts of these lesions.

Anemia↗

PubMed2000

Influence of different elastic moduli of dowel and core on stress distribution in root.

This study was carried out to investigate the influences of elastic moduli of the dowel-core combination on the stress distribution in the root by the use of 2-dimensional finite element analysis. The peak stress at the dowel-cement interface was influenced strongly by a change of elastic modulus of the post (from 20,000 kg/mm2 as a hard prefabricated post to 8,000 kg/mm2 as a custom cast post) for both vertical and 45 degree oblique loading (rho > 90%). Peak dentinal stress adjacent to the luting cement layer depended only on the post material for vertical loading (rho [symbol: see text] 99%). In contrast, the post and core materials (from 8,000 kg/mm2 as cast core to 300 kg/mm2 as composite resin core) acted in cooperation on the stress magnitude for oblique loading, but the influence of the core material was stronger than that of the post (rho of core [symbol: see text] 41% and rho of post [symbol: see text] 26%). On the other hand, at the marginal region the effect of the core material contributed more than 86% to the peak stress value for both loadings, and the post material affected at most about 11% of the bending resistance.

Algorithms↗

PubMed1999

Factors affecting membrane-controlled drug release for an osmotic pump tablet (OPT) utilizing (SBE)(7m)-beta-CD as both a solubilizer and osmotic agent.

PURPOSE: The purpose of this study was to define membrane controlling factors responsible for drug release from a controlled-porosity osmotic pump tablet (OPT) that utilizes a sulfobutyl ether-beta-cyclodextrin, (SBE)(7m)-beta-CD, as both a solubilizing and osmotic agent. METHOD: The OPT was spray coated with cellulose acetate solutions varying the amount and size of micronized lactose, the amount of triethyl citrate (TEC) and the composition ratio of dichlormethane to ethanol. Chlorpromazine (CLP) was used as a model drug. The release of CLP from the OPTs was studied using the Japanese Pharmacopoeia dissolution method. The membrane surface area of the OPTs were measured with multi-point analysis by the gas absorption method. RESULTS: The release rate of CLP from OPTs containing (SBE)(7m)-beta-CD increased with increasing amounts of micronized lactose and decreasing amounts of TEC and lactose particle size in the membrane. Also, the CLP release rates from the spray-coated OPTs using mixtures of varying ratios of dichlormethane to ethanol were almost identical. The membrane surface area of the OPTs following release of membrane components had a linear relationship to CLP release rates from the OPTs. CONCLUSION: The present results confirmed that the membrane controlling factors responsible for the drug release were the amount and size of micronized lactose and the amount of TEC in the membrane.

Antipsychotic Agents↗

PubMed1999

Release of testosterone from an osmotic pump tablet utilizing (SBE)7m-beta-cyclodextrin as both a solubilizing and an osmotic pump agent.

A controlled porosity osmotic pump system for poorly water soluble drugs has been developed using sulfobutyl ether-beta-cyclodextrin sodium salt, (SBE)7m-beta-CD, which can act as both a solubilizing and an osmotic agent. The release of testosterone, a poorly water soluble drug (0.039 mg/ml at 37 degrees C), was evaluated using a new model device. The effect of (SBE)7m-beta-CD as the solubilizing and osmotic pump agent was compared with hydroxypropyl-beta-cyclodextrin (HP-beta-CD), a neutral cyclodextrin, and a sugar mixture (osmotic agent only). Testosterone release from the device was significantly faster with (SBE)7m-beta-CD than with HP-beta-CD or the sugar mixture. The solubility of testosterone in the device increased to 76.7 mg/ml through complexation with (SBE)7m-beta-CD in the imbibed water. It appears that testosterone release from the device in the presence of (SBE)7m-beta-CD was mainly due to osmotic pumping while for HP-beta-CD the major contribution appears to be due to diffusion. In the case of the sugar mixture, testosterone was poorly released, presumably due to the absence of a solubilizer. Therefore, it was concluded that (SBE)7m-beta-CD provides novel properties for the development of controlled- porosity osmotic pump tablets for poor solubility drugs.

Algorithms↗

PubMed1999

Design and evaluation of an osmotic pump tablet (OPT) for chlorpromazine using (SBE)7m-beta-CD.

PURPOSE: The purpose of this study was to develop a controlled-porosity osmotic pump tablet (OPT) which exhibits pH-independent release profiles for a basic drug using a sulfobutyl ether-beta-cyclodextrin, (SBE)7m-beta-CD, which acts as both a solubilizer and as an osmotic agent. METHODS: Chlorpromazine free base (CLP) was chosen as a model drug for this study. The release of CLP from osmotic pump tablets was studied in vitro. In vivo absorption of CLP from the OPT was evaluated in male beagle dogs. RESULTS: The CLP release profile from an OPT prepared from a core tablet composed of a 1:10 molar ratio of CLP to (SBE)7m-beta-CD was pH-independent, and was controlled by modulating the membrane thickness of the OPT. Another cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and a sugar mixture of lactose and fructose resulted in pH-dependent release at the same molar ratio. An in vivo absorption study in dogs with an OPT containing (SBE)7m-beta-CD correlated very well with the in vitro release profiles using the Japanese Pharmacopoeia dissolution method. CONCLUSIONS: In addition to serving as a solubilizer and osmotic agent, (SBE)7m-beta-CD can also serve as the controlling agent for pH independent release of CLP from OPTs. This system successfully modified the in vivo input rate of CLP without compromising oral bioavailability.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1999

The effect of an oral prosthesis on the quality of life for head and neck cancer patients.

The quality of life (QOL) in patients with cancer in the head and neck regions has become an increasingly important factor in medical treatment. We examined the effect of a prosthesis on the QOL based on the patients' own subjective evaluations. Sixty-eight head and neck cancer patients who had been treated in the Department of Prosthetic Dentistry of the Faculty of Dentistry, Kyushu University, were compared with 35 denture wearers as a control. General denture satisfaction in the control group showed a statistical correlation with eating (P<0.01, t-test; rho = 0.72, Spearman rank correlation), aesthetic satisfaction (P<0.01, rho = 0.57) and pain (P<0.01, rho = 0.51). On the other hand, for cancer patients, general denture satisfaction showed a statistical correlation with not only eating (P<0.01, rho = 0.34), aesthetic satisfaction (P<0.01, rho = 0.33) and pain (P<0.01, rho = 0.41) but also health (P<0.01, rho = 0.33) and mental well-being (P<0.01, rho = 0.41). A statistical correlation between the Denture score and the QOL score was thus observed in cancer patients (P<0.0001, rho = 0.56), while the correlation for the control group was not statistically significant. This study showed that oral prostheses for head and neck cancer patients are important factors not only for eating but also for the overall patient QOL.

Adaptation, Psychological↗

PubMed1998

Design and evaluation of an osmotic pump tablet (OPT) for prednisolone, a poorly water soluble drug, using (SBE)7m-beta-CD.

PURPOSE: The purpose of this study was to develop a controlled-porosity osmotic pump tablet (OPT) for poorly water soluble drugs using a sulfobutyl ether-beta-cyclodextrin, (SBE)7m-beta-CD or Captisol, which acted as both a solubilizer and as an osmotic agent. METHODS: Prednisolone (PDL) was chosen as a model drug for this study. The release of PDL from osmotic pump devices and tablets was studied. In vivo absorption of PDL from OPT was evaluated in male beagle dogs. RESULTS: PDL release from the osmotic pump tablet with (SBE)7m-beta-CD was complete. Another cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and a sugar mixture of lactose and fructose resulted in incomplete release. Although PDL release from the OPT with (SBE)7m-beta-CD and the sugar formulation displayed mainly zero-order release characteristics, the tablet utilizing HP-beta-CD showed apparent first-order release characteristics. An in vivo absorption study in dogs correlated very well with the in vitro release profiles using the Japanese Pharmacopoeia dissolution method. CONCLUSIONS: The present results confirm that (SBE)7m-gamma-CD can serve as both the solubilizer and the osmotic agent for OPT of PDL, and modify the input rate of PDL without compromising oral bioavailability.

Absorption↗

PubMed1996

The interaction of charged and uncharged drugs with neutral (HP-beta-CD) and anionically charged (SBE7-beta-CD) beta-cyclodextrins.

PURPOSE: The objective of this work was to determine the role that charge might play in the interaction of charged and uncharged drugs with neutral (2-hydroxypropyl-beta-cyclodextrin, HP-beta-CD) and anionically charged (SBE7-beta-CD) modified beta-cyclodextrins. SBE7-beta-CD is a sulfobutyl ether, sodium salt, derivative variably substituted on the 2-, 3- and the 6-positions of beta-cyclodextrin. The number seven refers to the average degree of substitution. METHODS: The binding of the acidic drugs, indomethacin, naproxen and warfarin and the basic drugs, papaverine, thiabendazole, miconazole and cinnarizine with the two cyclodextrins was determined at 25 degrees C as a function of pH and cyclodextrin concentration by the phase-solubility method. RESULTS: Except for miconazole and cinnarizine (Ap-type diagrams), all other materials studied displayed AL-type diagrams. By comparing the binding constants of both the charged and uncharged forms of the same drugs to both HP-beta-CD and SBE7-beta-CD, the following conclusions could be drawn. The binding constants for the neutral forms of the drugs were always greater with SBE7-beta-CD than with HP-beta-CD. For the anionic agents, the binding constants between SBE7-beta-CD and HP-beta-CD were similar while the binding constants for the cationic agents with SBE7-beta-CD were superior to those of HP-beta-CD, especially when compared with the neutral form of the same drug. CONCLUSIONS: A clear charge effect on complexation, attraction in the case of cationic drugs and perhaps inhibition in the case of anionic drugs, was seen with the SBE7-beta-CD.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1988