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The incidence of peripheral pulmonary adenocarcinoma has increased in recent years. Clara cell has been known as target for carcinogens and source of pulmonary tumors. One of the presumed roles of the bronchiolar Clara cell is the secretion of pulmonary surfactant into the bronchiolar lumen. To establish the secretory morphology of Clara cell, a well-defined secretory agonist, isoproterenol (500 mg/kg) and the antagonist, propranolol (20 mg/kg), were administered into five-week old mice. The secretory response was examined at 1 hour and 4 hours after injection. Ultrastructural morphometry was used to quantitate the secretory response by measuring area of apical cap of the Clara cells. Isoproterenol caused a significant increase in area of apical cap of Clara cells 1 and 4 hours after injection (p<0.0001), while pretreatment with propranolol prevented this effect at 4 hours. Propranolol alone significantly decreased the area of Clara cells (p<0.0001). Clara cells secretory granules disappeared 1 hour after propranolol plus isoproterenol administration, and the granules reappeared at 4 hours. The accelerated secretion of Clara cells by isoproterenol provides evidence of their secretory mechanism controlled by beta-adrenergic agonists. The study has confirmed the secretory role of Clara cells. The secretion is both apocrine and merocrine type.departmental bulletin pape
Exposing neonatal rats with the synthetic estrogen, diethylstilbestrol (DES), induces morphological and functional abnormalities in the adult ovary. We examined the events that lead to this condition using female rats that were exposed to DES for the first five days after birth. The expression of steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage cytochrome P450 (P450scc), which are both required for steroidogenesis in the theca/interstitial region was markedly reduced. The expression of Müllerian inhibiting substance (MIS) was transiently increased in small growing follicles in the ovary of DES-treated rats at postnatal day 7 (P7), and the expression profile in the ovary differed between DES- and vehicle oil-treated rats at P14 and P21. The expression of the transcription factor, steroidogenic factor-1 (SF-1), reduced in theca/interstitial cells, but increased in granulosa cells of primary follicles. These results indicate that altered steroidogenesis and MIS production are mechanisms through which DES induces abnormal ovarian development, and support the notion that androgens and MIS are both critical factors in regulating early ovarian differentiation.departmental bulletin pape
The purpose of this study was to investigate the effects of oral care using simple tools and methods on the cleanliness of the oral cavity in the elderly. Enrolled were 84 elderly subjects with a mean (±S.D) age of 85.1±7.0 years in a nursing home. They were given tongue and oral mucosa cleaning (the oral care) after lunch every day or every other day for two consecutive weeks by the authors. The effect of the oral care was studied in terms of Candida scores in tongue coating, concentration of volatile sulfur compounds (VSC) which are the main causative substance of bad breath, and change in tongue coating scores. The above parameters were measured five times; just before the oral care program, weekly during, and at the end of the oral care program. The groups of patients, who were given the oral care, especially the group of patients cared with sponge brushes every day, showed a significant reduction in Candida scores but not in VSC concentration and tongue coating scores. The present method of oral care proved effective in cleaning the tongue and oral mucosa, and the Candida scores appeared to be a reliable indicator for evaluation. It is suggested that this way of oral care is simple, easy and useful not only for the elderly at a nursing home but for the house-bound elder people who will rapidly increase in the near future in Japan.departmental bulletin pape
The aim of this study is to examine the relation between mortality and the existence of incineration plants and dioxin released from the plants in 590 municipalities across Japan. The concentration of dioxins in emissions from incinerators, the amount of dioxins per population, the cumulative amount of dioxins, and the cumulative amount per land area were used as dioxin-related municipal indices. Age-adjusted mortality rates from all causes and five major disease categories by municipality in 1995 were used as health indices. The relation was examined using t-test, analysis of covariance (ANCOVA), correlation coefficients and multiple linear regression analysis, considering the effects of cities' socioeconomic conditions. Although municipalities with plants had significantly higher mortality from female stroke and lower mortality from male cancer at all site and lung than municipalities without plants, these differences were not significant in ANCOVA with socioeconomic indicators. The significant relation between mortality and dioxin indices in correlation coefficient was ruled out when the socioeconomic conditions were adjusted in multiple regression analysis. This study did not show the statistical relation between increased mortality from major causes and the existence of incineration plants and dioxins from the plants at the municipal level.departmental bulletin pape
The pharmacological actions of bisphosphonates are due to the inhibitory effects on bone resorption, but little is known about the bisphosphonate action on bone formation. The purpose of this study is to elucidate the actions of bisphosphonates, clodronate, on bone formation in the experimental in vivo and in vitro rat models. The bone mineral density (BMD) was decreased in the rats fed a low-calcium diet (0.05% Ca) for 6 days compared with the rats fed a normal-calcium diet (0.5% Ca). The decrease in BMD was suppressed in the 2 mgP/day and the 4 mgP/day clodronate administrations. Bone formation rate (BFR) in rats fed a low-calcium diet was significantly increased compared with the rats fed a normal-calcium diet, and the 2 mgP clodronate administration further increased the BFR. In the cultured rat bone marrow cells, the area of mineralized nodules was significantly increased at 10-7 and 10-6 M clodronate, but high concentration of clodronate decreased the area. From these results, it is concluded that clodronate stimulates bone formation when the drug was given to a rat with a relatively lower dose that is sufficient to prevent bone resorption and that this effect may be due to the stimulatory effect on the differentiation process of osteoblasts.departmental bulletin pape
Synovial chondromatosis of the temporomandibular joint is a rare disease, and extra-articular synovial condromatosis of the temporomandibular joint is even rarer. A review of the English literature from 1980 to 2000 has revealed 51 cases of synovial chondromatosis affecting the temporomandibular joint. We report a case of extra-articular synovial condromatosis, for which we carried out a long-term follow-up of the postoperative course using diagnostic images.departmental bulletin pape
Recurrent herpes labialis (RHL) occurs in up to 40% of the population. Although the disease is usually self-limiting, patients seek treatment because of the significant pain and visibility of the lesion. Xanthine oxidase inhibitors (XOI) have been reported to have a potent antiviral effect against influenza-A virus. We examined the effect of the systemic xanthine oxidase inhibitor, allopurinol, on RHL duration of illness, severity of symptoms, number and frequency of recurrence during a 4-year follow up period in Egyptian patients. Duration of illness was shortened by about 25%, early disappearance of pain and other symptoms occurred. Also, aborted episodes were noticed when allopurinol was given just after beginning of common colds, at the prodromal stage of RHL or during severe stress conditions. Patients receiving 3 courses of treatment had markedly decreased recurrences during the follow up period. Ex vivo experiments to examine virus-induced plaque formation on Vero cells in the absence or presence of different concentrations of the drug could not prove any direct anti herpetic effect of the drug. However, allopurinol seems to be safe and effective in reducing duration of RHL and to abort lesion or prevent its appearance in treated patients even when they experience immunosuppressive conditions.departmental bulletin pape
During orthodontic treatment, it is often necessary to move the hypofunctional teeth. In this study, we revealed an influence of orthodontic forces in the hypofunctional periodontal ligament, and focused on the distribution of proteoglycans, major extracellular matrix molecules. Five-week-old rats were divided into normal group and hypofunctional group. To induce occlusal hypofunction, occluding teeth of the mandibular first molar were extracted. At 8-week-old, orthodontic force by 15 or 2 gf titanium-nickel alloy closed coil spring was applied to the mandibular first molar toward the mesial direction. Immunohistochemical analysis was performed using antibodies for chondroitin sulfate (CS) and heparan sulfate (HS). In normal group, CS was observed throughout the extracellular matrix, while HS was observed on the endothelial cells and the osteoclastic cells on compressive side. In hypofunctional group without orthodontic appliance, CS and HS were detected in less amounts. With 15 gf, CS was observed at the compressive area where no cells and fibers were present, and HS was observed at the periphery of this area. With 2 gf, however, the distribution of CS and HS was similar to the normal control. These findings indicate that CS and HS were affected by orthodontic forces, and suggest their distinct functions in tissue remodeling.departmental bulletin pape
MMP-13 appears to be one of the most importantMMPs in cartilage remodeling and mineralization,because it exhibits a substrate preference for thecartilage-specific type II collagen. The condylarprocess is constructed by rapid accumulation ofhypertrophic chondrocytes during development,but its mechanism is still unclear. To investigate therole of MMP-13 in developing condylar cartilage, weimmunohistochemically examined the localizationof MMP-13 in the endochondral ossification of themandibular condyle and tibiae of newborn mice. Inthe tibiae, the MMP-13 expression was detectedonly in the deepest layer of the terminal hypertrophicchondrocytes through every examinedstage (day 1 to day 10 after birth). On the otherhand, in the condylar cartilage at days 1 and 5,MMP-13 was expressed throughout the proliferatingand the hypertrophic chondrocytes, and atday 10, MMP-13 was mainly localized in the deepestedge of the hypertrophic layer. A zymographicalstudy showed that the activity of MMP-13 in thecondyle was observed at day 1, earlier than in thetibia, and increased until day 7. The time-dependentand cell-specific expression of MMP-13 and itsenzymatic property suggest that in the mandibularcondylar cartilage, MMP-13 plays a role in makingthe space for cell enlargement by degradation ofthe cartilage matrix and in onset of mineralizationduring the early stage of development.departmental bulletin pape
Etiology of sarcoidosis remains unknown. A trigger factor from Propionibacterium acnes causes a cellular immune response in some sarcoid patients but not in nonsarcoid subjects. We examined whether experimentally induced hypersensitivity to the trigger factor gives rise to granulomas. Female C57BL/6 mice primed intravenously with P. acnes or not were sensitized with recombinant-protein RP35, a fragment of P. acnes trigger factor, and complete Freund's adjuvant. In controls, RP35 was replaced with P. acnes or one of two control proteins. In primed and unprimed mice, pulmonary granulomas were found in some of the mice sensitized with RP35 or P. acnes but in no control-protein-sensitized mice. Detection of pulmonary granulomas (25-57%) did not differ significantly between mice sensitized with RP35 or P. acnes, primed or not. No difference in popliteal lymph-node-cell reactivity and serum antibodies to these two antigens was found between mice with and without pulmonary granulomas. P. acnes was cultured from the lungs of 8 (33%) of 24 untreated mice. The recombinant trigger-factor protein of P. acnes caused pulmonary granulomas in primed and unprimed mice sensitized with the protein and adjuvant. Sarcoid granulomas may form during hypersensitivity to antigens of P. acnes indigenous to the affected organ.departmental bulletin pape