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Biomedical subjects

M Miyauchi

Publications and source records attributed to M Miyauchi.

At least 91 records · Page 5Linked to original sources

Three-dimensional appearance of Langerhans cells in human gingival epithelium as revealed by confocal laser scanning microscopy.

Detailed three-dimensional morphological information of the cell without distortion due to thin sectioning can be obtained from thick sections using a confocal laser scanning microscope. Here that microscope was used to evaluate human gingival Langerhans cells stained with anti-CD1a antibody. Optical sectioning and reconstruction by laser scanning microscopy revealed not only three-dimensional aspects of Langerhans cells but also spatial information on the distribution of their dendritic processes towards the gingival surface. The orientated configuration of those processes may reflect the reaction of the gingival Langerhans cell to the surrounding moist environment containing antigenic stimuli originating in saliva.

Antibodies↗

Aortic stump closure with a titanium permanent clamp: a useful emergency method.

Successful aortic stump closure in a patient with Behçet's disease was accomplished with a permanent titanium clamp. In May 1990, a saccular infrarenal abdominal aortic aneurysm was detected in this patient, and prosthetic graft replacement was carried out. One year later, this graft was removed because of perigraft fluid collection; the aortic stump was sutured closed, and a right axillobifemoral bypass was done. In November 1994, the patient was admitted to the hospital because of an aortoenteric fistula. An emergency operation was performed, and the aortic stump was managed successfully with a permanent clamp. In patients with Behçet's disease, use of a permanent clamp may offer an alternative to traditional methods for closing blown-out aortic stumps.

Anastomosis, Surgical↗

Nitrogen-containing furanose and pyranose analogues from Hyacinthus orientalis.

Aqueous methanol extracts from the bulbs of Hyacinthusorientalis were subjected to various ion-exchange column chromatographic steps to give 2(R),5(R)-bis(hydroxymethyl)-3(R),4(R)-dihydroxypyrrolidine (DMDP) (1), 2,5-dideoxy-2,5-imino-dl-glycero-d-manno-heptitol (homoDMDP) (2), 2,5-imino-2,5,6-trideoxy-d-manno-heptitol (6-deoxy-homoDMDP) (3), 2,5-imino-2,5,6-trideoxy-d-gulo-heptitol (4), 1-deoxynojirimycin (5), 1-deoxymannojirimycin (6), alpha-homonojirimycin (7), beta-homonojirimycin (8), alpha-homomannojirimycin (9), beta-homomannojirimycin (10), and 7-O-beta-d-glucopyranosyl-alpha-homonojirimycin (MDL 25,637) (11). The structures of the new natural products 3 and 4 were determined by spectroscopic analysis, including extensive 1D and 2D NMR studies. Compound 2 was found to be a potent inhibitor of bacterial beta-glucosidase, mammalian beta-galactosidases, and mammalian trehalases, while 3 was a potent inhibitor of rice alpha-glucosidase and rat intestinal maltase. Compound 4 was observed to be a good inhibitor of alpha-l-fucosidase.

Alkaloids↗

Upregulation of nucleobindin expression in human-activated lymphocytes and non-Hodgkin's lymphoma.

Nucleobindin (Nuc) was originally found to be an enhancement factor of anti-DNA antibody production secreted by a lymphoid cell line derived from a lymphoproliferative MRL/lpr mouse. It has been shown that Nuc has a unique structure containing a DNA- and two calcium-binding domains, and a leucine zipper motif, but its biological roles have not yet been fully elucidated. Expression of Nuc was first studied in human lymphocytes. Expression of Nuc mRNA in normal peripheral blood mononuclear cells was significantly increased upon mitogen stimulation. Anti-human Nuc monoclonal antibody H-1D8 immunoprecipitated Nuc protein in the nuclear extract of Molt-4 cells. Furthermore, in the immunohistochemical staining of tumor specimens from 108 patients with non-Hodgkin's lymphoma (NHL) with H-1D8, H-1D8-positive cells were observed in nearly all cases in varying frequency. According to the Working Formulation, the percentage of cases in which more than 90% of the tumor cells were stained with H-1D8 was 65% in the high grade of the histological malignancy, 54% in the intermediate grade, and 22% in the low grade; however, normal cells surrounding the tumor cells were virtually negative for H-1D8. These results showed that the level of Nuc expression in human lymphocytes reflects the status of activation or proliferation of the cells, thus providing a clue for the further investigation into biological roles of Nuc. In addition, it might be applicable to the clinicopathological estimation of NHL as a novel indicator.

Adolescent↗

Clear cell odontogenic tumour: a case with induction of dentin-like structures?

A case of clear cell odontogenic tumour, which occurred centrally in the mandible of a 56-year-old Japanese woman, is reported with its histochemical, immunohistochemical and ultrastructural findings. Histologically, the tumour nests were composed of large glycogen-rich clear cells and small non-clear polygonal cells and were separated by thin mature fibrous connective tissue septae. Immunohistochemically, both types of tumour cells showed positive expression of various cytokeratins, in particular cytokeratin 19, and of epithelial membrane antigen. Eosinophilic hyaline deposits and possible dentin-like structures were occasionally formed in contact with the epithelial nests and are regarded as indicative of the epithelial-mesenchymal inductive capacity of this tumour. The aggressive nature of the present tumour was assumed through its invasive growth pattern and occasional mitotic figures. Although it was diagnosed as clear cell odontogenic tumour according to the present WHO classification, the patient must be followed carefully because of its probable malignant nature.

Connective Tissue↗

Localization of glycosaminoglycans (GAGs) in pleomorphic adenoma (PA) of salivary glands: an immunohistochemical and histochemical evaluation.

The tumor matrix of salivary pleomorphic adenoma (PA) is characteristically rich in glycosaminoglycans (GAGs), which contribute to its complex histoarchitecture. This study evaluated the microscopic localization of various GAGs in 17 PAs, using a panel of anti-GAG monoclonal antibodies and biotinylated hyaluronic acid (HA)-binding protein. Both epithelial and mesenchymal-like tissues were confirmed to contain GAGs. Luminal epithelial cells mostly lacked GAGs, whereas GAGs were seen both in the cytoplasm and cell membrane of non-luminal epithelial cells. In addition, small intercellular accumulations of GAGs were often present in solid epithelial areas, implying the epithelial origin of GAGs. GAGs did not appear to be a main component of the hyaline matrix. The myxoid region was consistently stained for both chondroitin 6-sulfate (CS-6) and HA but variably for chondroitin 4-sulfate (CS-4), dermatan sulfate (DS) and keratan sulfate (KS); heparan sulfate (HS) was not detected. The chondroid region showed increased staining for CS-6 but reduced staining for HA when compared with the myxoid region. In addition, CS-4, DS and KS were seen both in chondroid cells and the territorial matrix, whereas HS was present only in the cells. It is suggested that GAGs in PA are mainly produced by non-luminal cells and influence the proliferation, differentiation, secretory activity and shape of tumor cells, thus contributing to the morphological diversity of this tumor.

Adenoma, Pleomorphic↗

Distribution of macrophage lineage cells in rat gingival tissue after topical application of lipopolysaccharide: an immunohistochemical study using monoclonal antibodies: OX6, ED1 and ED2.

To discuss the role of macrophage lineage cells on the periodontal tissue destruction, we immunohistochemically examined the phenotype and the dynamics of macrophage lineage cells 1 or 3 h or 1, 2, 3 or 7 d after topical application of LPS (5 mg/ml in physiological saline) from the rat gingival sulcus using 3 monoclonal antibodies: OX6 (antigen-presenting cells), ED1 (monocytes, macrophages and dendritic cells) and ED2 (resident macrophages). We could detect at least 3 different types of macrophage lineage cells, namely OX6+/ED1+/ED2- dendritic cells and exudate macrophages and ED2+ resident macrophages. After LPS application the majority of macrophage lineage cells accumulated in the subjunctional epithelial area were newly extravasated OX6+/ED1+/ED2- dendritic cells or macrophages. The number of these cells increased progressively with time and reached a maximum level at d 2. On the other hand, number and tissue distribution of ED2+ resident macrophages did not change. These results indicate that several types of macrophage lineage cells exist in rat gingival tissue and suggest that dendritic cells and exudate macrophages transiently accumulated after LPS application are responsible for various host immune response and tissue destruction caused by LPS.

Administration, Topical↗

Impaired tumorigenicity of IL-4-producing murine neuroblastoma cells in immunodeficient nude mice.

We have examined antitumor effect of murine neuroblastoma cells (C1300) retrovirally transduced with interleukin-4 (IL-4) gene in syngeneic A/J and nude mice. Although in vitro proliferation of IL-4-secreting C1300 cells (C1300/IL-4) was not different from that of wild-type cells, the in vivo tumor growth of C1300/IL-4 cells subcutaneously inoculated into immunocompetent A/J mice was retarded compared with that of wild-type cells and consequently, the survival of the A/J mice which received C1300/IL-4 cells was prolonged. In immunodeficient nude mice we observed accelerated growth rate of wild-type tumors in comparison with the tumors developed in A/J mice. In contrast, the tumor growth of C1300/IL-4 cells in nude mice was significantly suppressed and the growth was much slower than that of C1300/IL-4 cells inoculated in A/J mice. Thus, the secretion of IL-4 from tumor cells produced antitumor effect more efficiently in mature T cell-defective hosts than in immunocompetent mice. Our results suggest a possible clinical application of IL-4 expression in tumor cells via genetic manipulations especially in immunocompromised cancer patients.

Animals↗

Synthesis and structure-activity relationships of 1beta-methylcarbapenems with quaternary ammonium side chains.

The synthesis and antibacterial activity of 1beta-methylcarbapenems with quaternary ammonium groups at the C-2 position have been studied. Two types of new carbapenem derivatives have been synthesized. These 1beta-methylcarbapenems, one type having a (2S,4S)-2-[1,1-dimethyl-2-(1-piperazinyl)carbonyl]pyrrolidinio-4-+ ++ylthio group and the other type having a (2S,4S)-2-(4-carbamoylmethyl-4-methylhomopiperazinio-1-yl carbonyl)pyrrolidin-4-ylthio group, show potent and well balanced antibacterial activity as well as high stability against dehydropeptidase-I. The in vivo potency of these two carbapenems was compared with that of meropenem. The structure-activity relationships leading to these carbapenems are also described.

Animals↗

Specific alpha-galactosidase inhibitors, N-methylcalystegines--structure/activity relationships of calystegines from Lycium chinense.

An examination of the roots of Lycium chinense (Solanaceae) has resulted in the discovery of 14 calystegines, a cycloheptane bearing an amino group and three hydroxyl groups, and two polyhydroxylated piperidine alkaloids. Calystegines A7 and B5, in addition to the previously known calystegines A3, A5, A6, B1, B2, B3, B4, C1, C2 and N1, were isolated and determined as 1alpha,2beta,4alpha-trihydroxy-nortropane and 1alpha,2alpha,4alpha,7alpha-tetrahydroxy-nort ropane, respectively. L. chinense also had two polyhydroxytropanes bearing a methyl group on the nitrogen atom, unlike the previously reported nortropane alkaloids. They were established as N-methylcalystegines B2 and C1, and their N-methyl groups were found to be axially oriented from NOE experiments. 1Beta-amino-3beta,4beta,5alpha-trihydroxycyclohepta ne was also present in L. chinense and may be a biosynthetic precursor of the calystegines that occur in this plant. Two polyhydroxypiperidine alkaloids, fagomine and 6-deoxyfagomine, were isolated. Calystegine B2 is a potent competitive inhibitor of almond beta-glucosidase (Ki = 1.9 microM) and coffee bean alpha-galactosidase (Ki = 0.86 microM), while N-methylcalystegine B2 was a more potent competitive inhibitor of the latter enzyme (Ki = 0.47 microM) than the parent compound but showed a marked lack of inhibitory activities towards most other glycosidases. Since this compound is a very specific inhibitor of alpha-galactosidase and inhibits rat liver lysosomal alpha-galactosidase with a Ki of 1.8 microM, it may provide a useful experimental model for the lysosomal storage disorder, Fabry's disease. The addition of a hydroxyl group at C6exo, as in calystegines B1 and C1, enhances the inhibitory potential towards beta-glucosidase and beta-galactosidase but markedly lowers or abolishes inhibition towards alpha-galactosidase. Hence, the N-methylation of calystegine C1 did not enhance its inhibition of alpha-galactosidase. The chemical N-methylation of calystegines A3 and B4 markedly enhanced inhibition of coffee bean alpha-galactosidase, with Ki values of 5.2 microM and 36 microM, respectively, but almost eliminated their inhibitory potential towards beta-glucosidase and trehalase, respectively. Thus, methylation of the nitrogen atom significantly altered the specificity of the inhibitors.

Animals↗

Reactive change in proliferative activity of the junctional epithelium after topical application of lipopolysaccharide.

IT IS WELL ESTABLISHED THAT apical migration of junctional epithelium (JE) along a root surface is an important factor in periodontal pocket formation and deepening. However, the exact mechanism and, more specifically, the role of inflammatory products in influencing the activity of cells within the JE is not known. To address this issue lipopolysaccharide (LPS) was applied topically into rat molar gingival sulcus and then tissues evaluated immunohistochemically for expression of proliferating cell nuclear antigen (PCNA). Tissues were prepared for histological analysis at designated times. Histologically, infiltration of neutrophils with associated edema was noted in JE and gingival connective tissues 6 hours after LPS application and was prominent at 12 hours. These inflammatory changes persisted in the 2- and 3-day specimens, and disappeared at 5 days. In normal gingiva, before the LPS application, the JE showed few PCNA positive cells, while almost all cells in the basal and suprabasal cell layers of the oral gingival epithelium and the oral sulcular epithelium were PCNA positive. No increase in the number of PCNA positive cells in the JE beyond zero time was observed at 6 and 12 hours after LPS application. One day after LPS application, PCNA positive cells appeared in the basal cell layer of the JE, with a continued increase number of PCNA positive cells in the JE continued at 2 and 3 days. By day 5 the number of PCNA positive cells were decreasing with return to a normal range by 7 days. These results showed that 1) under normal physiological conditions, cells within the JE have minimal mitotic activity and 2) the JE cells can enter the proliferating cell cycle when exposed to LPS, and suggest that the enhanced proliferating activity in the JE is an important factor for the deepening of the periodontal pocket, if the connective tissue attachment is broken down.

Animals↗

Synthesis and structure-activity relationships of a novel oral carbapenem, CS-834.

We have studied an ester prodrug of a carbapenem to develop a potent orally active beta-lactam antibiotic. A variety of 1 beta-methylcarbapenem derivatives have been synthesized. We have found that some derivatives having an amide group in the C-2 side chain show potent and well balanced antibacterial activities as well as high stability against dehydropeptidase-I. Oral absorption of derivatives has been optimized by modifying the C-3 ester promoiety. Pivaloyloxymethyl (1R, 5S, 6S)-6-[(R)-1-hydroxyethyl]-l-methyl-2-[(R)-5-oxopyrrolidin-3-yl thio]- l-carbapen-2-em-3-carboxylate, CS-834, has been selected as the most promising compound for further evaluation.

Administration, Oral↗

[Ocular complications of atopic dermatitis].

We examined the frequency and types of ocular complications that developed in 560 eyes of 280 patients with atopic dermatitis at the Department of Dermatology, Tokyo Medical College Hospital. Mild ocular involvement included blepharitis in 294 eyes (52.5%), conjunctivitis in 221 eyes (39.5%), and superficial punctate keratopathy in 65 eyes (11.6%). More serious ocular complications leading to decreased visual function occurred in 133 eyes (23.8%) that developed lens opacities, and 34 eyes (6.0%) that developed retinal break or retinal detachment. Because of the presence of abnormalities in the peripheral retina, we believe that a pathogenic factor may have been present in the vitreous of these atopic dermatitis patients. Many of our patients with atopic dermatitis had serious ocular complications in the absence of ocular symptoms. Thus it is important to conduct a thorough ophthalmological examination in the early period of disease in atopic dermatitis patients, both for the management of early but serious ocular complications, as well as for the preservation of visual function.

Adolescent↗

Augmentation with serum thymic factor of suppressive effects on retroviral tumor development in hosts immune to v-onc product.

Inbred adult female rats were immunized against syngeneic ST-FeSV induced sarcoma cells. ST-FeSV was injected subcutaneously into 57 neonates (vaccinated) born from these immunized females and into 60 non-vaccinated syngeneic neonates. Serum thymic factor (FTS) was injected subcutaneously into 10 of vaccinated and 30 of non-vaccinated rats. Sarcomas developed in 40.4% (19/47) of vaccinated (A), 20.0% (2/10) of vaccinated FTS injected (B), 63.3% (19/30) of non-vaccinated FTS injected (C), and 76.7% (23/30) of non-treated (D) rats. By AB immunostaining using antibody to v-fes product (P85), sarcomas developed in 10 of 13 rats of group C tested, and 3 of 6 rats of group D tested were positive, but those in 7 rats of group A and 2 rats of group B tested were all negative. Lung metastasis was observed in rats of all groups except those of B group. All sera of animals that developed sarcomas were positive to P85 in Western blot analysis. These results showed that FTS augmented suppressive effects on sarcoma development in hosts immune to the viral oncogene product.

Animals↗

Immunohistochemical demonstration of prostaglandins in various tissues of the rat.

To demonstrate the tissue localization of prostaglandin (PG) E2, PGF2 alpha and 6-keto-PGF1 alpha (a stable metabolite of PGI2) various tissues, including decalcified periodontal tissue of 7-week-old male Wistar strain rats, were immunohistochemically examined using a streptavidin-biotin complex method. Besides tissue macrophages and endothelial cells in various tissues, hepatocytes, renal tubular cells, and parietal and chief cells in the gastric mucosa showed a positive reaction for the various PGs examined. PGs were demonstrated in the cytoplasm or in association with the cell membrane. We generally observed no difference between the localization patterns of PGE2-, PGF2 alpha-, and 6-keto-PGF1 alpha-positive cells in these tissues. However, in the periodontal ligament and alveolar bone, 6-keto-PGF1 alpha was localized in the cytoplasm of osteocytes, osteoblasts, cementocytes, and cementoblasts, while no reaction for PGE2 or PGF2 alpha was revealed in these cells. We demonstrated the immunohistochemical localization of PGs in various rat tissues including decalcified periodontal tissue and discuss the important roles of PGs in the modulation of their normal functions in these tissues.

Animals↗