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Biomedical subjects

H Moriyama

Publications and source records attributed to H Moriyama.

At least 127 records · Page 7Linked to original sources

IL-4 and IL-6 production of bone marrow-derived mast cells is enhanced by treatment with environmental pollutants.

To examine the potential effects of environmental pollutants on the production of cytokines in mast cells, mouse bone marrow-derived mast cells (BMMC) were cultured at various concentrations of diesel exhaust particulates (DEP) or formaldeyhde. Proliferation of BMMC at 0.8, 2 and 4 microg/ml of DEP and 0.5 and 1 microg/ml of formaldehyde did not differ significantly from that of the controls (0 microg/ml) after 72 h culture, with the exception of a significant decrease in proliferation at 5 microg/ml of formaldehyde. Treatment with DEP or formaldehyde alone did not induce interleukin-4 (IL-4) or IL-6 production by BMMC. IL-4 and IL-6 production in BMMC stimulated with A23187 was higher in BMMC treated with low concentrations of DEP than in controls, but no increase was seen in BMMC treated with high DEP. IL-4 and IL-6 production in A23187-stimulated BMMC was significantly increased at 0.5 and 1 microg/ml formaldehyde but decreased at 5 microg/ml formaldehyde. After pretreatment with low DEP or formaldehyde alone for 24h, IL-4 production of BMMC stimulated with A23187 was lower in BMMC treated with low DEP or formaldehyde than in controls. Antigen-induced IL-4 production significantly increased in BMMC treated with 0.4 or 0.8 microg/ml DEP or 0.5 microg/ml formaldehyde, but antigen-induced IL-6 production in BMMC did not increase at low DEP or formaldehyde. Although the enhancement of IL-4 production of BMMC stimulated with A23187 plus DEP was not completely inhibited by 5x10(-4) M 2-mercaptoethanol (2-ME), treatment with 10(-7) M dexamethasone inhibited further IL-4 production. Cytokine production of mast cells is thus shown here for the first time to be modulated by treatment with DEP or formaldehyde. Environmental pollutants such as DEP and formaldehyde may thus affect the immune response via the modulation of cytokine production in mast cells.

Animals↗

Efficient and beta-stereoselective synthesis of 4(5)-methyl-5(4)-(5-amino-5-deoxy-beta-D-ribofuranosyl)imidazole and related compounds exhibiting antiulcer activity.

The reaction of 2,3,5-tri-O-benzyl-D-ribose with the lithium salt of an imidazole derivative gave an adduct 17RS. Treatment of 17RS with 1.5N HCl in refluxing tetrahydrofuran gave the beta-4(5)-ribofuranosylimidazole 19 (35%) and the ribosylimidazole 18 (51%). The latter was converted into beta-19 in 86% yield by the Mitsunobu cyclization. This synthetic method produced only the desired beta-anomer. Protection of the imidazole nitrogen of 19 with an ethoxycarbonyl group followed by debenzylation gave 21, which was successively derived to the 5'-amino derivative 1 via the 5'-substituted phthalimide 23, followed by hydrazine degradation in excellent yield. Compound 1 was then converted into the 5'-cyanoguanidine 2 in 79% yield. The 5'-amino derivatives 3-9 lacking a methyl group were efficiently synthesized. Among them, the cyanoguanidine 5 and phenylthiourea 8 exhibited antiulcer activities with half the efficacy of cimetidine. The molecular conformation of 5 was determined by X-ray structure analysis.

Animals↗

Morphometric analyses of axons in the lateral corticospinal tract with ageing process.

Morphometric analyses were carried out to reveal a relation between age and axonal changes in the lateral corticospinal tract (LCST) at the L1 level of the human spinal cord. Histological preparations of the spinal cord were made after embedding in celloidin to stain with Luxol fast blue-periodic acid-Schiff-hematoxylin or Klüver-Barrera methods. The number, average transverse area, total area and diameter of axons of the LCST were counted and measured using an image-analyser combined with a computer. The morphometric analyses revealed that (1) there was a significant decrease in the axonal number of the LCST with age (p < 0.001); (2) the axons were not partially nor completely accompanied by surrounding myelin sheaths, and increased in number with age; (3) the diameter and average area of axons in the LCST became significantly reduced with age (p < 0.01); (4) the total area decreased significantly with age in a unit area of 2,700 microns2; and (5) the circularity ratio showed no significant change with age.

Adult↗

Immunohistochemical study of extracellular matrices and elastic fibers in a human sternoclavicular joint.

In this study, we clarified the distribution of elastic and oxytalan fibers in a human sternoclavicular joint (SCJ) using a color image system and in extracellular matrices using immunoperoxidase staining. Fine elastic fibers (EFs) were scattered in the fibrous layer of the sternoclavicular disk. This articular disk was composed of a collagenous bundle on the sternum side of the articular disk in the SCJ and cellular components including connective tissue on the clavicular side of the articular disk. The thickness of the disk gradually increased from the inferior to superior portion. Collagen fibers type I, III and V and other extracellular matrices (ECMs) were detected in the hypertrophic zone in the clavicular and sternum side of the SCJ and in the connective tissue of the articulatio condylar. On the cervical surface of the articular disk, cellular activity was higher than on the sternum surface.

Adult↗

Expression of macrophage colony-stimulating factor and its receptor in hepatic granulomas of Kupffer-cell-depleted mice.

In mice administered with liposome-entrapped dichloromethylene diphosphonate, which depletes Kupffer cells, the size and the number of zymosan-induced granulomas in the liver were smaller than in untreated mice. The number of macrophage precursors, as detected by the monoclonal antibodies for macrophage precursors, increased after zymosan injection in both groups of mice, proliferated, and differentiated into macrophages. Expression of macrophage colony-stimulating factor (M-CSF), interleukin-1, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and interferon-gamma mRNA was enhanced in the stage of granuloma formation in the control mouse liver, whereas it was suppressed in Kupffer-cell-depleted mice. However, M-CSF mRNA expression was increased in the Kupffer-cell-depleted mice to form granulomas in the late stages. In situ hybridization demonstrated the expression of M-CSF mRNA and c-fms mRNA in Kupffer cells and monocyte-derived macrophages in the sinusoid and granulomas. The concentration of M-CSF in serum of zymosan-injected control mice was within normal range, but that of zymosan-treated or untreated Kupffer-cell-depleted mice was markedly elevated at day 1. These findings imply that Kupffer cells are indispensable for granuloma formation and produce various cytokines including M-CSF. The local production and consumption of M-CSF in the liver may play a crucial role in granulomatous inflammation.

Animals↗

[A study on low grade malignant tumors arisen in the trachea and the bronchus].

Twelve patients who suffered from low grade malignant tumors arisen in the trachea and the bronchus (6 of carcinoid, 4 of mucoepidermoid carcinoma, and 2 of adenoid cystic carcinoma) underwent surgical treatment from 1977 to 1996 in our department. Operations included 1 sleeve resection of the trachea, 1 patch plasty of the trachea, 3 sleeve lobectomies, and 7 lobectomies. Lymph node dissection was performed in 9 of 12 cases. Metastases in lymph nodes were not found in all 12 cases. Five year survival rate of low grade malignant tumors arisen in the trachea and the bronchus was 78.8% and better than that of stage I lung cancers.

Adolescent↗

[Relationship between the morphological changes of Japanese cedar (Cryptomeria japonica) pollen grains and the release of major allergens from the pollen].

Release of major allergens (Cry j 1, Cry j 2) from Japanese cedar (C. japonica) pollen grains treated with high pressure was investigated. C. japonica pollen grains crushed by high pressure treatment using FRENCH Pressure Cell Press released greater amounts of major allergens, particularly Cry j 2, compared to those without crush. This suggests that the cytoplasm of C. japonica pollen grains contains more Cry j 2 than previously reported. The effect of nasal fluid on the release of major allergens from C. japonica pollen grains was analyzed in vitro. Nasal fluid from patients with nasal allergy remarkably increased the release of major allergens from pollen grains, compared to controls, and the amount of Cry j 1 was greater than Cry j 2. Further studies revealed that nasal fluid affects the outer wall of pollen grains, where Cry j 1 is located, to a greater extent than its effect on the cytoplasm, where Cry j 2 is located.

Allergens↗

Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway.

The present study demonstrated that a short-term administration of mAbs against leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) at critical periods resulted in complete protection of autoimmune diabetes in non-obese diabetic (NOD) mice. When these mAbs were administered for only 6 days at 2 wk of age, neither diabetes nor insulitis was observed at 30 wk of age. It appears that the tolerance against beta cell Ag(s) was induced by this transient blockade of the LFA-1/ICAM-1 pathway. Protective suppressor activity was not enough to prevent diabetes because co-transfer of splenocytes from female NOD mice, which had received these mAbs at 2 wk of age, resulted in only a short delay of the diabetic onset caused by adoptive transfer of splenocytes from acutely diabetic NOD mice. Transfer of these splenocytes to young NOD mice could not also abrogate the spontaneous diabetes and insulitis. Furthermore, cyclophosphamide treatment could not abrogate the protection. When splenocytes from the treated NOD mice were transferred to NOD-SCID mice, none of the recipient mice developed significant insulitis and subsequent overt diabetes, suggesting the absence or the inactivation of diabetogenic effector T cells. However, splenic T cells from the insulitis-free NOD mice that had received the mAb treatment preserved proliferative responses to both islet cells and 65-kDa glutamic acid decarboxylase (GAD65) in vitro. These results suggest that a unique peripheral tolerance was induced by the transient blockade of the LFA-1/ICAM-1 pathway in an early age of NOD mice.

Adoptive Transfer↗

Cryocrystallography of 3-Isopropylmalate dehydrogenase from Thermus thermophilus and its chimeric enzyme.

The crystal structures of thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus (10T) and a chimeric enzyme between T. thermophilus and Bacillus subtilus with one point mutation (cS82R), were determined at both 100 and 150 K. At the cryogenic condition, the volume of the unit cell decreased by 5% as a result of a contraction in the solvent region. Although the overall structures of both enzymes at low temperature were the same as that of 10T at room temperature, interactions between two domains and between two subunits in a functional dimer of cS82R were significantly altered. The decrease in the average temperature factor of 10T at low temperature and no significant decrease for cS82R suggested that the structure of the engineered enzyme (cS82R) may have many conformational substates even at low temperature, while the native enzyme (10T) at low temperature has a more definite conformation than that at room temperature. The location of water molecules around the enzyme molecule and the calculation of the radii of gyration suggested that cS82R had a weaker hydration than 10T.

Journal Article↗

Structure of a loop-deleted variant of 3-isopropylmalate dehydrogenase from Thermus thermophilus: an internal reprieve tolerance mechanism.

A loop-deleted mutant form of 3-isopropylmalate dehydrogenase from Thermus thermophilus was constructed to investigate the relationship between the flexibility of the structure and the thermostability of the enzyme. The structure of the mutant enzyme was determined by X-ray crystallography and was found to be almost the same as that of the native enzyme with a reduced temperature factor. Although the mutant protein had lost the flexible loop, its function and thermostability had remained unchanged. This phenomenon can be explained by an internal reprieve tolerance mechanism.

Journal Article↗

Expression of messenger RNA for keratinocyte growth factor in human cholesteatoma.

OBJECTIVE: To understand the interaction between cholesteatoma epithelium and subepithelial connective tissue as a paracrine regulation by keratinocyte growth factor. DESIGN: Preparation of a specific DNA probe from human fetal fibroblast and detection of localization of keratinocyte growth factor messenger RNA in subepithelial granulation tissue of middle-ear cholesteatoma by a nonradioactive in situ hybridization method. PARTICIPANTS: The cholesteatoma specimens were excised from 12 patients during surgery. Normal skin specimens collected from the external ear canal of six patients were used as controls. RESULTS: Signals specific for keratinocyte growth factor messenger RNA were not expressed in the normal skin of the external ear canal, but were observed in fibroblasts of subepithelial connective tissue of cholesteatoma specimens. Signals were observed only in specimens collected from patients whose subepithelial connective tissue was thick and proliferated and whose inflammation was strong. CONCLUSIONS: A paracrine regulation mechanism involving keratinocyte growth factor may exist for proliferation of epithelium of cholesteatoma. The subepithelial connective tissue of cholesteatoma may play an important role in the proliferation and development of the cholesteatoma, especially under inflammatory conditions.

Base Sequence↗

Development, differentiation, and phenotypic heterogeneity of murine tissue macrophages.

In murine ontogeny, macrophage precursor cells develop in the yolk sac and fetal liver. Primitive macrophages also appear in the yolk sac, migrate to various tissues, and differentiate into several fetal macrophage populations. Because the development of the monocytic cell lineage is incomplete in the early stage of fetal hematopoiesis, primitive/fetal macrophages are considered to originate from granulocyte-macrophage colony forming cells or earlier macrophage precursors, bypassing the early monocytic cell series. In adult mice rendered severely monocytopenic by administration of strontium-89, resident macrophages are maintained by self-renewal. In contrast, administration of liposome-encapsulated dichloromethylene diphosphonate (clodronate) results in the elimination of various tissue macrophage populations. The repopulation of affected macrophages is dependent on the increase of precursors in the liver and spleen during the period of macrophage depletion. Such precursors reconstitute heterogeneous macrophage subpopulations. In mice homozygous for the osteopetrosis (op) mutation, the absence of macrophage colony-stimulating factor (M-CSF) activity results in a deficiency of monocytes and monocyte-derived macrophages. However, immature macrophages are present in various tissues. Administration of M-CSF to op/op mice induces the increased proliferative capacity and the morphological maturation of macrophages. However, the responses of individual tissue macrophage subpopulations to M-CSF are different. These results indicate that macrophage development, differentiation, and proliferation are regulated by the tissue microenvironment including the in situ production of macrophage growth factors in both fetal and adult life.

Animals↗

Liposome-encapsulated dichloromethylene diphosphonate induces macrophage apoptosis in vivo and in vitro.

Dichloromethylene diphosphonate (MDPCl2) encapsulated in multilamellar liposomes was selectively incorporated by macrophages, immediately transferred to lysosomes, then released from liposomes into lysosomes by enzymatic digestion of the liposomal lipid layers. From 4 h after ingesting liposome-encapsulated MDPCL2 murine macrophages in vivo and in vitro acquired the ultrastructural features of apoptosis, such as condensed nuclear chromatic, nuclear fragmentation, cell shrinkage, and blebbing of the plasma membrane. Murine peritoneal macrophages and isolated rat Kupffer cells incubated in the medium containing liposome-encapsulated MDPCl2 increased DNA fragmentation in a dose-dependent manner. Electrophoretic analysis of extracted DNA from the isolated Kupffer cells showed DNA fragmentation. Another diphosphonate, Alendronate (4-amino-1-hydroxy-butylidene-1,1-diphosphonate) had less potent macrophage cytotoxicity. However, MDPCl2, Alendronate, and gadolinium chloride in solution were not cytotoxic to macrophages. These results implied that the intralysosomal accumulation of MDPCl2 generates signals to induce macrophage apoptosis.

Alendronate↗

Stringently and developmentally regulated levels of a cytoplasmic double-stranded RNA and its high-efficiency transmission via egg and pollen in rice.

A very restricted amount of high-molecular-weight double-stranded RNA (dsRNA) has been found in healthy japonica rice plants. We discriminated dsRNA-carrying rice plants from noncarriers. The endogenous dsRNA was localized in the cytoplasm (about 100 copies per cell) and was transmissible to progeny plants by mating. In crosses between carriers and noncarriers, the RNA was transmitted efficiently to F1 plants via both egg and pollen. The rice dsRNA was maintained at an almost constant level by host plant cells from generation to generation. The high-efficiency transmission of the endogenous dsRNA to progeny plants appears to depend on the autonomously controlled replication of the dsRNA localized in cytoplasmic vesicles. However, an increase in copy number (about 10-fold) of the dsRNA was observed during the suspension culture of host cells. The number of copies of dsRNA returned to the original low value in regenerated plants, suggesting that the copy number is stringently and developmentally regulated in rice cells.

Crosses, Genetic↗

Crystal structure of H2-proteinase from the venom of Trimeresurus flavoviridis.

The crystal structure of the zinc-protease, H2-proteinase, isolated from the venom of Trimeresurus flavoviridis has been determined. The crystallographic R factor is 0.176 for 10,635 reflections with Fobs > 2sigma(Fobs) in the 8.0 to 2.2 Angstrom resolution range. The enzyme has two domains with a cleft in which a catalytic zinc atom is located. The N-terminal domain is composed of four helices around a central five-stranded beta-sheet. The irregularly folded C-terminal domain contains one helix and two disulfide bridges. These two domains are linked by a disulfide bridge. In the zinc environment, the catalytic zinc atom forms a distorted tetrahedral coordination with three histidines and one catalytic water molecule, and the methionine-containing turn is structurally conserved. These are distinctive features of the metzincins, one of the zinc metalloprotease superfamilies. The entire structure shows good agreement with that of two Crotalus snake venom proteases, adamalysin II and atrolysin C. The H2-proteinase, however, contains no structural calcium ions, and differences of disulfide configurations and the coordination of the catalytic water molecule exist as compared with the other two proteases.

Amino Acid Sequence↗

[A case of empyema caused by Salmonella enteritidis in a patient with sequela of pulmonary tuberculosis].

A 69-year-old male was admitted to our hospital on Jan. 10, 1995 complaining of bloody sputum, left back pain and fever of 39 degrees C. He had a history of pulmonary tuberculosis 45 years ago. His chest X-ray and CT showed the presence of air-fluid level in the left pleural cavity with thickening and calcification of the pleura. Salmonella Enteritidis was isolated from the sputum, bronchoalveolar lavage fluid and stool. He was diagnosed as suffering from Salmonella-empyema with an internal fistula. Based on the in vitro sensitivity test, sulfamethoxazole/trimethoprim was started. However, the efficacy of the antimicrobia was not sufficient. He then underwent left pleuropneumonectomy. Salmonella was cultured also from the specimen obtained at the operation. His course after operation was uneventful. Thus, although Salmonella Enteritidis is known as a common pathogen of food poisoning, it can cause empyema, especially in a case with an impaired host defence system.

Aged↗

Demonstration of the nasal septal branches of the sphenopalatine artery by use of a new intravascular injection method.

We injected a new injection material into the external carotid artery using a new method, which led to the successful demonstration of the nasal septal branches of the sphenopalatine artery in human cadavers. The result shows the trunk of the artery divided into three main branches, the upper two of which run toward Little's area. We believe that the knowledge of septal branches, shown in a photograph, is very useful, not only for nasal treatment, but also for anatomic demonstration to students.

Aged↗