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Biomedical subjects

M Miyauchi

Publications and source records attributed to M Miyauchi.

At least 73 records · Page 4Linked to original sources

Promoting effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone on rat glandular stomach carcinogenesis initiated with N-methyl-N'-nitro-N-nitrosoguanidine.

The modifying effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a mutagenic by-product in chlorinated water, on the development of glandular stomach cancers were investigated in Wistar rats. A total of 120 males, 6 weeks of age, were divided into six groups. After initiation with 100 ppm N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) solution and 5% NaCl diet for 8 weeks, 30 rats each in groups 1-3 were given MX in the drinking water at concentrations of 30, 10, or 0 ppm for the following 57 weeks. Ten animals each in groups 4-6 were administered the MX without prior carcinogen exposure. There were no statistical significant differences in final body weights between the groups. The incidences and multiplicities of adenocarcinomas in the glandular stomachs were significantly higher (P < 0.05) in the initiated 30 ppm MX group than those in the MNNG/NaCl group. The incidences of atypical hyperplasias in the glandular stomachs were also significantly increased (P < 0.05 or 0.01) by the MX treatments. With their multiplicity, the effects were clearly dose dependent. Interestingly, the 30 ppm MX alone itself induced atypical hyperplasias in the pylorus, although the incidences and severity were low. Moreover, MX showed a tendency to enhance the development of intrahepatic cholangiocellular tumors and thyroid follicular cell tumors in the MNNG-treated animals. The results of the present study thus indicate that MX exerts promoting effects when given during the postinitiation phase of two-stage glandular stomach carcinogenesis in rats.

Adenocarcinoma↗

Polyhydroxylated pyrrolidine and pyrrolizidine alkaloids from Hyancinthoides non-scripta and Scilla campanulata.

Aqueous ethanol extracts from the immature fruits and stalks of bluebell (Hyacinthoides non-scripta) were subjected to various ion-exchange column chromatographic steps to give 1,4-dideoxy-1,4-imino-D-arabinitol (1),2(R),5(R)-bis(hydroxymethyl)-3(R),4(R)-dihydroxypyrrolidine (DMDP) (2), 6-deoxy-6-C-(2,5-dihydroxyhexyl)-DMDP (3),2,5-dideoxy-2,5-imino-DL-glycero-D-manno-heptitol (homoDMDP)(4),homoDMDP-7-O-apioside (5), homoDMDP-7-O-beta-D-xylopyranoside (6), (1S*,2R*,3R*,5R*,7aR*)-1,2-dihydroxy-3,5- dihydroxymethylpyrrolizidine (7), and (1S*,2R*,3R*,5R*,6R*,7R*,7aR*)-3-hydroxymethyl-5-methyl-1,2,6,7 tetrahydroxypyrrolizidine (8). Bulbs of Scilla campanulata (Hyacinthaceae) yielded (1S*,2R*,3R*,5S*,7aR*)-1,2-dihydroxy-3,5-dihydroxy-methylpyrrol izidine (9) in addition to compounds 1-7. Compounds 3,6,7,8, and 9 are new natural products. Compound 4 is a potent competitive inhibitor with K(i) values of 1.5 microM for Caldocellum saccharolyticum beta-glucosidase and 2.2 microM for bovine liver beta-galactosidase. The 7-O-beta-D xyloside 6 was a stronger competitive inhibitor than 4 of C saccharolyticum beta-glucosidase and rat intestinal lactase, with K(i) values of 0.06 and 0.07 microM, respectively, but a weaker inhibitor of bovine liver beta-galactosidase. Furthermore, compound 4 is also a competitive inhibitor (K(i) = 1.8 microM) of porcine kidney trehalase, but 6 was inactive against this enzyme.

Alkaloids↗

Mismatch negativity and N2b attenuation as an indicator for dysfunction of the preattentive and controlled processing for deviance detection in schizophrenia: a topographic event-related potential study.

The present study compares the amplitudes and topographic patterns of mismatch negativity (MMN) and N2b in schizophrenic patients and normal controls. Twenty-one schizophrenic outpatients and 19 normal volunteers participated in the study. Event-related potentials (ERPs) were recorded in a selective attention task. During the task, subjects were required to focus on one ear, counting deviant stimuli, those deviating in duration from a sequence of standard stimuli. MMN was significantly attenuated in the schizophrenics as compared with the normals in the frontocentral regions. In addition to MMN, the N2b amplitude was also reduced, which showed a significant correlation with the MMN amplitude in the schizophrenics. The late negativity elicited by the deviant stimuli in the unattended condition showed different topographical features between the groups. Whereas the normals showed a lateralized distribution with an ear-related asymmetry, similar to that of the N2b, the schizophrenics showed a frontal dominance, coinciding with the sustained negativity reported by Näätänen et al. (1982), which reflects the automatic preparation for detecting possible subsequent stimulus changes. The amplitude of the sustained negativity was significantly correlated with the performance level in the schizophrenics. The results indicated that although both preattentive and controlled processings are impaired, schizophrenic patients, presumably due to the deficient controlled processing, owe much to automatic processing in the deviant stimulus detection process.

Acoustic Stimulation↗

Immunohistochemical and histochemical characterization of the mucosubstances of odontogenic myxoma: histogenesis and differential diagnosis.

To discuss the dental origin of odontogenic myxoma and to provide further information for the differential diagnosis between this tumor and myxoid malignant fibrous histiocytoma (MFH) which occasionally occurs in jaw bones, the contents of glycosaminoglycans (GAGs) and proteoglycans (PGs) in the mucosubstances of 15 odontogenic myxomas, 5 myxoid MFH and 3 human fetal tooth germs in the bell stage of development were characterized using histochemical and immunohistochemical methods. Histochemical staining of hyaluronic acid (HA) was undertaken using biotinylated HA binding protein (B-HABP), and immunohistochemical detection was done using a panel of antibodies against chondroitin 6-sulfate (CS-6), chondroitin 4-sulfate (CS-4), dermatan sulfate (DS), keratan sulfate (KS), heparan sulfate (HS), aggrecan, PG-M/versican, decorin and biglycan. In odontogenic myxoma, CS-6, HA and PG-M/versican were observed in the myxomatous matrix of all cases, while KS and HS were seen in none. As for CS-4, DS, aggrecan, decorin and biglycan, only irregular and mild stainings were shown. Consistent and strong positive straining for CS-6, HA and PG-M/versican were seen in dental papilla and provided evidence supporting the origin of this tumor from dental papilla. Except for the constant staining for HA, the myxoid matrix was rarely stained for most GAGs and PGs in myxoid MFH. Immunodetection of CS-6 and PG-M/version with the use of monoclonal antibodies 3-B-3 and 2-B-1 is therefore recommended as a useful tool in differentiating odontogenic myoma from myxoid MFH.

Diagnosis, Differential↗

Clinical and histopathological analyses of desmoplastic ameloblastoma.

Desmoplastic ameloblastoma (DA) is an unusual subtype of ameloblastoma characterized by pronounced desmoplastic stroma. There is, however, still argument whether DA is a distinct clinicopathologic entity. To enhance knowledge of DA, 7 cases of DA (7.9%) were retrieved from 89 ameloblastomas field in the Department of Oral Pathology, Hiroshima University School of Dentistry and analyzed clinicopathologically and histopathologically. The mean age of the patients with DA and non-DA at the time of the diagnosis was 40.6 +/- 5.9 years and 33.1 +/- 2.0 years, respectively. The male-to-female ratio was 2.5:1 in DA and 1.8:1 in non-DA. Four (57%) DAs were located in the maxilla where only 6% of the non-DA occurred. Interestingly, all DAs arose in the anterior/premolar area of the jaws and 6 cases were located mainly within the alveolus. None of the DA showed typical radiographic features of ameloblastoma. In 5 DAs, scattered radiopacities were observed in the radiolucent lesion and gave preoperative diagnoses of non-ameloblastomatous lesions or even osteosarcoma. All DAs showed pronounced desmoplastic stroma where there were compressed tumor islands usually lacking a peripheral layer of ameloblastic cells and a central zone of stellate reticulum. There was cystic change within the epithelial nests in 3 DAs and true glandular structures with mucus cells in a case of DA. Tumor islands often infiltrated into marrow spaces of surrounding bone. There was no capsule formation. Recurrence rate was 14% in DA and 20% in non-DA. The present study based on data of DA in the Japanese population supports that DA must be considered as a distinct clinicopathologic entity.

Adolescent↗

In vivo targeted gene transfer into liver cells mediated by a novel galactosyl-D-lysine/D-serine copolymer.

A novel synthetic polypeptide designed as a DNA binding-molecule for liver-specific, receptor-mediated, gene transfer was used to selectively introduce reporter genes into liver cells in the form of plasmid DNA-ligand complexes. The polypeptide was a D-lysine/D-serine copolymer (Lys/Ser = 33/36 or 53/60) modified with a polyethylene glycol 5000 at the carboxyl-terminus (PLSP). In addition, the lysine epsilon-amino groups were covalently bound to galactose (galactosyl-PLSP), a ligand for the asialoglycoprotein receptor on hepatocytes. Solutions of DNA-ligand complex were prepared by adding solutions of DNA and galactosyl-PLSP in a mixing ratio of DNA:galactosyl-PLSP = 1:3 (w/w). Following injection of the DNA-ligand complex into mice via the tail vein, high levels of luciferase and enhanced green fluorescent protein, which were encoded by the reporter genes, were observed in liver. In contrast, luciferase activity in kidney, spleen, lung and heart was negligible. The high levels of gene expression obtained with DNA/galactosyl-PLSP complexes were achieved without partial hepatectomy or administration of lysosomotrophic agents. Thus, the synthetic Lys/Ser copolymer used in the present study appears to be a promising new tool which enhances the efficacy of receptor-mediated gene transfer into hepatocytes and which may provide another step toward the clinical practice of organ-specific gene therapy.

Animals↗

So-called 'hybrid' lesion of desmoplastic and conventional ameloblastoma: report of a case and review of the literature.

So-called 'hybrid' lesion of ameloblastoma, which is composed of desmoplastic ameloblastoma and conventional follicular/plexiform ameloblastoma, is an unusual variant of ameloblastoma and only eight cases of 'hybrid' lesion have been published in the English literature. To enhance knowledge of this interesting tumor, we add a case of 'hybrid' lesion that occurred in the right mandible of a 48-year-old Japanese male. Radiographic examination disclosed a honeycomb appearance at the anterior alveolar region, combined with a unicystic radiolucency in the molar region of the mandibular body. Histologically, the former showed microscopic features of desmoplastic ameloblastoma and the latter those of follicular ameloblastoma with focal granular cell transformation. The lesion was enucleated with curettage of surrounding bone and the lesional cavity was marsupialized. Although tumor tissues reappeared at 3, 5, 7 and 14 months after the surgery, the patient has remained disease free for 11 years after the last vaporization by CO2 laser of the recurred tumor. Many more cases of 'hybrid' lesion are needed to clarify the clinicopathological, histopathological and biological characteristics of this interesting variant of ameloblastoma.

Ameloblastoma↗

Alteration of perceived fragrance of essential oils in relation to type of work: a simple screening test for efficacy of aroma.

The perceptional change of fragrance of essential oils is described in relation to type of work, i.e. mental work, physical work and hearing environmental (natural) sounds. The essential oils examined in this study were ylang ylang, orange, geranium, cypress, bergamot, spearmint and juniper. In evaluating change in perception of a given aroma, a sensory test was employed in which the perception of fragrance was assessed by 13 contrasting pairs of adjectives. Scores were recorded after inhaling a fragrance before and after each type of work, and the statistical significance of the change of score for 13 impression descriptors was examined by Student's t-test for each type of work. It was confirmed that inhalation of essential oil caused a different subjective perception of fragrance depending on the type of work. For example, inhalation of cypress after physical work produced a much more favorable impression than before work, in contrast to orange, which produced an unfavorable impression after physical work when compared with that before work. For mental work, inhalation of juniper seemed to create a favorable impression after work, whereas geranium and orange both produced an unfavorable impression then. From these studies, together with those conducted previously with lavender, rosemary, linalool, peppermint, marjoram, cardamom, sandalwood, basil and lime, we thus concluded that the sensory test described here might serve not only as a screening test for efficacy of aroma but also as a categorized table for aroma samples which can act as a reference to each other.

Adult↗

Frequent expression of midkine gene in esophageal cancer suggests a potential usage of its promoter for suicide gene therapy.

We have examined the expression of midkine (MK), a neurotrophic factor with heparin-binding activity, in human esophageal cancer cells. Seven esophageal cell lines tested expressed the transcript and 8 out of 14 human esophageal tumor specimens were positively stained with anti-MK antibody, while surrounding normal esophageal tissues in these specimens were not stained. The 5'-flanking, 2.3 kb genomic region of the MK gene was shown to drive the transcription of a reporter gene in the esophageal cell lines in a cis acting manner. Forced expression in esophageal cancer cells of herpes simplex virus-thymidine kinase gene mediated by the flanking region of the MK gene conferred sensitivity to a prodrug, ganciclovir. The 5'-upstream region of the MK gene thus possesses putative promoter activity which can be used for suicide gene-based gene therapy for esophageal cancer.

Aged↗

Periodontitis in the house musk shrew (Suncus murinus): a potential animal model for human periodontal disease.

BACKGROUND: Our understanding of periodontal diseases has been facilitated greatly by the use of animal models. However, no animal model has been identified that truly reflects the disease seen in humans. Suncus murinus, a rat-sized laboratory house musk shrew, has received attention as a valuable animal model due to ease of handling. In the studies described here, periodontal conditions in Suncus murinus were evaluated to determine the usefulness of the shrew as an experimental model for understanding various aspects of periodontal diseases. METHODS: Periodontal tissues of 34 Suncus murinus (18 to 430 days old) were examined macroscopically, morphometrically, histologically, and ultrastructurally. RESULTS: Dentition pattern is I3/1, C1/1, P2/1, M3/3. Spontaneous gingival swelling with accumulation of plaque was observed in more than two-thirds of animals older than 200 days. Morphometric analysis of alveolar bone demonstrated a pattern of bone loss that correlated closely with animal age. Histologically, periodontal lesions varying from gingivitis to periodontitis, similar to those observed in humans, were noted. Marked infiltration of lymphocytes and plasma cells in the connective tissue was noted, usually not seen in periodontal lesions of rodents. Although osteoclastic alveolar bone resorption was noted, active bone resorption was not a frequent feature in specimens obtained from chronic inflammatory lesions. Ultrastructurally, degradation of collagen fibers in the inflamed area and ingestion of collagen fibrils by fibroblasts in the deeper connective tissue were often seen. CONCLUSIONS: These results indicate the potential utility of Suncus murinus as a model to study periodontal disease; e.g., chronic nature of the inflammatory periodontal lesions, similar to those in humans, as well as other advantages including size and ease of handling and housing of these animals.

Age Factors↗

Synthesis and biological evaluation of new oral carbapenems with 1-methyl-5-oxopyrrolidin-3-ylthio moiety.

The synthesis and biological properties of 1beta-methylcarbapenems with 1-methyl-5-oxopyrrolidin-3-ylthio group at the C-2 position were studied. The sodium (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[(R)-1-methyl-5-oxopyrro lidin-3-ylthio]-1-carbapen-2-em-3-carboxylate and its (S)-isomer at the 2-position show potent and well-balanced antibacterial activity. The pharmacokinetic parameters of the pivaloyloxymethyl esters of these two carbapenems were compared in mice. The in vivo potency of these carbapenems was compared with that of cefdinir. Good in vivo efficacy of these ester prodrugs reflected the high and prolonged blood levels in parent drugs achieved after oral administration to mice.

Administration, Oral↗

Ontogeny of the rat parietal cell: analysis using anti-parietal cell antibody and transmission electron microscopy.

We studied the ontogeny of the rat parietal cell using human anti-parietal cell antibody and transmission electron microscopy. In the gastric fundus of the rat, we found that the epithelium changed from stratified to columnar at gestational day 18.5. Gastric pits began to form at gestational day 19.5. Primitive fundic glands appeared at gestational day 20.5. Human anti-parietal cell antibody specifically stained the rat parietal cells. By this immunohistochemical staining, rat parietal cells were identified from gestational day 19.5. At first we observed only a few plump parietal cells sparsely located in the fundic glands. In neonatal rats, the parietal cells increased in number and began to distribute themselves over a wider area of the primitive fundic glands especially in the lower half. As the rats grew, the distribution area of the parietal cells expanded to cover the whole of the glands except for the foveolar region. Parietal cells in the isthmus and neck regions were round and plump, while those in the basal region were slender and polygonal. We found that throughout the development of the fundic glands there were several ultrastructural changes of the parietal cells. In the late fetal period, parietal cells containing lysosomes and secretory granules were observed, but no tubulovesicles were identified. Development of the tubulovesicles was remarkable until one week after birth. The ultrastructure of the parietal cells of the neonate and adult varied, depending on their distribution area. We found that parietal cells in the basal region of the fundic glands which are fully matured cells had wider intracellular secretory canaliculi, while cells in the upper region had narrower canaliculi; this indicates the functional difference between hydrochloric acid secretion in parietal cells of the two regions.

Aged↗

[A 13-week subchronic toxicity study of D-xylose in F344 rats].

A 13-week subchronic toxicity study of D-xylose was performed in male and female F344 rats at dose levels of 0%, 0.2%, 0.6%, 1.7%, and 5% D-xylose in the CRF-1 powder diet to determine the maximum tolerable dose (MTD) for subsequent investigation of carcinogenicity. Rats were randomly allocated to 5 groups each consisting of 10 males and 10 females. Rats were randomly allocated to 5 groups each consisting of 10 males and 10 females. No treated groups showed changes in body weight gain or food intake, and all animals survived until the end of the experiment. Hematological examination revealed significant increases in RBC, Hb, and Ht in the male groups treated with 0.6% and 5% concentrations, whereas these values decreased significantly in all of the female groups treated with D-xylose. However, no clear dose-response effect was observed in the hematological data in either males or females given D-xylose. Serum biochemistry studies revealed decreases in AsT in the 0.2% and 5% D-xylose group male and 0.2%, 1.7%, and 5% group female, compared to the control value. However, the changes were not considered specific because of the lack of any clear dose-response effect. In addition, no histopathological changes indicating obvious toxicity of D-xylose were observed in the livers of either sex treated with D-xylose. Based on these data, the MTD of D-xylose in F344 rats of both sexes is judged to be 5% or more in the diet.

Administration, Oral↗

[A 90-day subchronic oral toxicity study of Bacillus subtilis gum in F344 rats].

A 90-day subchronic toxicity study of Bacillus subtilis gum was performed in both sexes of F344 rats by feeding of CRF-1 pellet diet containing 0%, 0.18%, 0.55%, 1.66% and 5%. Rats were randomly allocated to 5 groups, each consisting of 10 males and females. No animals died during the administration period and no differences in body weights and food intakes were found among groups of either sex. Kidney weight was significantly increased in both sexes in the groups given concentrations of 1.66% or more. However, the increases of kidney weight were slight in themselves and other data on serum biochemistry and histopathology did not show any apparent toxicological signs including renal toxicity. These findings indicate that the treatment of Bacillus subtilis gum in the diet for 90 days does not exert serious toxicity in rats even at the highest dose.

Animals↗

[A 13-week subchronic oral toxicity study of orange color in F344 rats].

A 13-week subchronic toxicity study of orange color was performed in both sexes of F344 rats by feeding them a CRF-1 powder diet containing 0%, 0.18%, 0.55%, 1.66%, and 5% concentrations of the substance. No animals died during the administration period, and no changes in body weight or food intake were found in any of the dosage groups. There were significant increases in serum cholesterol in males given 1.66% or higher concentrations of orange color and in females given 0.55% or higher concentrations, and significant increases in alkaline phosphatase in males given 1.66% or higher concentrations, possibly due to the high-fat composition of the orange color diets. In addition, some hematological, serum biochemical, and histopathological changes were observed in the groups given greater than 0.55% concentrations, but they did not suggest obvious toxicity. These findings indicate that under these experimental conditions the no-observed-effect level (NOEL) of orange color in the diet for 13 weeks is 0.18% and the no-observed-adverse-effect level (NOAEL) is 5%.

Administration, Oral↗

Reduced expression of cyclin-dependent kinase inhibitor p27Kip1 is an indicator of malignant behavior in oral squamous cell carcinoma.

BACKGROUND: Reduced expression of the cyclin-dependent kinase inhibitor p27Kip1 has been reported to correlate with poor survival in cohorts of breast and colorectal carcinoma patients. Posttranslational ubiquitin-mediated proteasomal proteolysis is related to p27Kip1 protein levels. However, to the authors' knowledge, no previous study has examined the expression of p27Kip1 in oral squamous cell carcinoma (OSCC). METHODS: To examine the expression of p27Kip1 and its clinicopathologic roles in OSCC, the authors studied the expression of p27Kip1 protein by immunohistochemistry in deparaffinized tissue sections of 20 normal oral mucosa specimens, 22 epithelial dysplasia specimens, and 70 OSCCs, and analyzed its correlation with clinicopathologic parameters. They also studied the expression of p27Kip1 mRNA and protein in six OSCC cell lines by Northern blot and Western blot analysis. To examine the mechanism of reduced expression of p27Kip1, OSCC cell lines were treated with the proteasome inhibitor LLnV. RESULTS: All the normal oral mucosa specimens and 73% (16 of 22) of the oral epithelial dysplasia specimens expressed p27Kip1 at high levels, whereas 87% of the OSCCs (61 of 70) showed reduced expression of p27Kip1. Furthermore, the levels of expression of this protein were significantly lower in carcinomas with metastasis than those without metastasis. Although OSCC cell lines expressed p27Kip1 mRNA at various levels, most of them expressed p27Kip1 protein at lower or undetectable levels. LLnV induced the expression of p27Kip1 protein in HSC2 cells, in which p27Kip1 protein was originally undetectable. CONCLUSIONS: These findings suggest that 1) reduced expression of p27Kip1 may correlate with the development and progression of OSCC and can be an indicator of malignant behavior of this neoplasm, and 2) increased proteasome-mediated degradation may play an important role in the reduction of p27Kip1 protein expression.

Adult↗

Immunocytochemistry and in situ hybridization studies of pepsinogen C-producing cells in developing rat fundic glands.

The ontogeny of pepsinogen C-producing cells in rat fundic glands was studied by means of light and electron microscopy using an antiserum raised against a synthetic peptide based on rat pepsinogen C. To confirm the immunocytochemistry results, the expression of rat pepsinogen C messenger RNA (mRNA) in the fundic gland was also examined by in situ hybridization using a digoxigenin-labeled RNA probe. In adult rats, pepsinogen C was produced by chief cells, mucous neck cells, and intermediate mucopeptic cells. Pepsinogen C-producing cells appeared in embryos as early as 18.5 days' gestation. The development of these cells could be classified into four stages: (1) 18.5 days' gestation to 0.5 days after birth; (2) 0.5 days to 2 weeks after birth; (3) 3-4 weeks after birth; (4) 4-8 weeks after birth. In embryos and young animals, pepsinogen C-producing cells were mucopeptic cells. By 4 weeks after birth, mucous neck cells could be distinguished morphologically. The maturation stages of the chief cells could be traced by electron microscopy along the longitudinal axis of the rat fundic gland by double-staining with anti-pepsinogen C antibody and periodic acid-thiocarbohydrazide-silver proteinate. Positive reactions for pepsinogen C and pepsinogen C mRNA expression were detected in mucous neck cells. Therefore, we conclude that mucous neck cells are precursor cells of chief cells. Mucous neck cells, intermediate cells, and chief cells are in the same differentiating cell lineage.

Animals↗

Mesh plug repair for a small incisional hernia in a cirrhotic patient with ascites: report of a case.

We report herein the case of a patient with severe liver ascites due to cirrhosis in whom a small incisional hernia on a midline incision was successfully treated by a mesh plug repair, a method most commonly employed for groin hernia repair. The hernia sac was dissected and inverted into the abdominal cavity by the mesh plug under epidural anesthesia. The patient's recovery was quick and relatively painless, and there has been no recurrence after 1 year of followup. This case report demonstrates that the method of mesh plug repair may be appropriate for small incisional hernias as well as groin hernias, performed under epidural anesthesia.

Ascites↗