Vietnamese type 2 diabetic subjects with normal BMI but high body fat.
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Biomedical subjects
Publications and source records attributed to Kaoru Kusama.
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Telomerase, one of the reverse transcriptases that extend telomere length, has been suggested to facilitate tumorigenesis and tumor immortality. Little is yet known, however, concerning the clinical significance of telomerase expression in brain tumors. We found in the present study that telomerase expression may contribute to malignant progression and can be an important indicator of high grade diffusely infiltrating astrocytomas, and its quantitated activity level reflects their growth potential. Telomerase expression and its quantitated activity level are also a good predictor of clinical course as compared with other biological markers and clinical factors.
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The objective of the present study was to evaluate the feasibility of using a calcium phosphate cement (CPC) in the reconstruction of a defective alveolar ridge in conjunction with implant placement. The CPC consisted of an equimolar amount of tetracalcium phosphate and dicalcium phosphate anhydrous. At the beginning of the experiment, all mandibular premolar teeth of mature beagle dogs were extracted. After 1 month of healing, alveolar bone was reduced to make a space for a CPC block that was prefabricated from a CPC mixed with water at a powder/liquid ratio of 5 g/mL. After an additional month, 8-mm long hydroxyapatite-coated titanium implants were placed in such a way that the apical half was embedded into alveolar bone and the coronal half in the preformed CPC block. The dogs were sacrificed and biopsies were obtained at 1, 3, and 6 months after surgery. Sections that included implants were evaluated for integration of the CPC block to the alveolar bone and of the implant to the alveolar bone. Additional sections without the implants served as controls. The results obtained from this study show that the CPC ridge augmentation gradually is replaced by natural bone. Six months after surgery, histopathologic features of the augmentation area were quite similar to those of natural alveolar bone. The coronal half of the implants, previously surrounded by the CPC block, was firmly fixed by natural bone. Therefore, this method may be useful for increasing the height of the alveolar ridge.
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Two cases are presented of a central odontogenic fibroma (OF) in the mandible of a middle-aged female, which posed considerable difficulty in microscopic diagnosis. These well-demarcated but non-encapsulated intraosseous tumors had hybrid features of both OF and ameloblastoma. Their clinical findings are more in keeping with the putative OF rather than ameloblastoma. The present lesions alert pathologists to this unusual type of central OF in order to avoid misdiagnosis.
We present a previously undescribed, intravenously occurring papillary hemangioma of the lip in a 10-year-old girl. Maze-like anastomosing capillary loops were found within the numerous, dilated veins widely distributed in the submucosa. These peculiar endovascular papillae of bland endothelial cells plugged the lumens and bore a striking resemblance to the renal glomeruli. Thrombi or other associated vascular lesions could not be identified. Because of its histological similarity to endovascular papillary angioendothelioma-like tumor, we designate this tumor as endovascular papillary hemangioma.
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The authors present an interesting and unusual histology of compound odontoma from an 18-year-old female. Part of the subepithelial connective tissue beneath the enamel organ epithelium was replaced by a granular cell nodule, of a probable histiocytic nature. This case represents the first published report of odontoma accompanied by granular cells.
Our previous histopathological study showed that the augmentation block, prepared from a calcium phosphate cement (CPC) mixed with H2O at powder to liquid ratio of 5 g/mL, placed on the alveolar bone ridge, was gradually replaced by natural bone. In the present study, fluorescent labeling analysis (FLA) and electron probe microanalysis (EPMA) were performed on the same surgical site of the above histopathological study. Fluorescent labeling agents, that would be incorporated into newly formed mineralized tissues, were injected into dogs intramuscularly twice a week during the 3 week period that ended 1 week before sacrifice. The specimens obtained from the block were subjected to FLA for assessing the extent of new bone formation and to EPMA for measuring the elemental (Ca, P, Mg) distributions. FLA results showed the presence of newly formed bone at 1 month after surgery. EPMA results showed that the elemental distributions in the augmentation site were similar to those of the residual bone area at 6 months after surgery. FLA and EPMA examinations also indicated that the implants were surrounded and fixed by natural bone chronologically. A CPC augmentation block is clearly useful for alveolar ridge augmentation and osteointegrated implant fixation.
Dendritic cells (DCs) are antigen-presenting cells that initiate and modulate immune responses, including tumor immunity. In this study we examined, immunohistochemically, the distribution of DC subsets in the primary tumor, adjacent tissue and regional lymph nodes (RLNs) of patients with oral squamous cell carcinoma (OSCC). The numbers of S100+ and CD1a+ DCs in tissue adjacent to the primary tumor were greater in patients without metastasis to RLNs (PN- cases), compared with those with metastasis (PN+ cases), while greater numbers of CD83+ DCs in the primary tumors were found in PN+ cases. In the RLNs, the numbers of S100+ and CD1a+ DCs were less in PN+ cases than in PN- cases, while the numbers of CD83+ DCs were greater in PN+ cases compared with those in PN- cases. These results suggest that the distribution of DC subsets in OSCC may reflect the degree of tumor immunity induced in the host bearing OSCC.
BACKGROUND: The role of p53 during the evolutionary steps of experimental salivary gland tumorigenesis has not been fully elucidated. MATERIALS AND METHODS: Each genotype group of p53-deficient mice received a single intrasubmandibular gland injection of 1 mg of 7, 12-dimethylbenz(a)anthracene. In addition to the routine histopathological examination, immunohistochemical detection of p53 protein and molecular biological analysis of wild-type p53 allele status in the p53+/- tumors developed were performed. RESULTS: Fourteen weeks following injection, submandibular gland tumors developed in 100% of p53-/- and 70% of p53+/- mice, whereas only 10% of p53+/+ mice yielded tumors. Salivary gland tumors in p53-deficient mice were predominantly sarcomas (70%). In 64% of p53+/- tumors, overexpression of a mutant version of p53 protein was evident. Loss of the wild-type allele of p53 could not be detected in all p53+/- tumors. CONCLUSION: The earlier tumor development in p53-deficient mice provides the in vivo evidence that reduction of p53 dosage or possibly p53 haploinsufficiency might be sufficient to promote salivary gland tumorigenesis.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/APO2L) is a novel member of the tumor necrosis factor cytokine family and a potent inducer of apoptosis in tumor cells. TRAIL is expressed in most normal human cells and tissues, including peripheral blood leukocytes, spleen, lung and prostate. However, TRAIL expression in human neoplasms is largely unknown. In this study, we investigated whether TRAIL and its receptors are expressed in human oral squamous cell carcinomas (HOSCCs) or HOSCC cell lines (HSC-2, HSC-3, HSC-4, Ca9-22 and KB) and whether these cells are sensitive to TRAIL-induced apoptosis. TRAIL and its receptor transcripts and proteins were detected in all HOSCC cell lines. A cell viability (MTT) assay performed after exposure to recombinant human (rh) TRAIL for 16 h showed that KB cells were the most sensitive. Immunohistochemical examinations for TRAIL expression were also carried out in a total of 50 HOSCC cases with various types of differentiation. In 17 of 27 WHO Grade 1 SCCs, the tumor invasive areas with keratinization showed diffuse and moderate TRAIL expression. In 6 of 20 WHO Grade 2 SCCs, TRAIL expression was slightly to moderately detected. In 1 of 3 WHO Grade 3 SCCs, a slight TRAIL expression was observed. Thus, there is considerable heterogeneity of TRAIL expression and susceptibility to TRAIL-induced apoptosis among human oral tumors.
Possible changes in the intracellular concentrations of polyamines were investigated during the apoptosis of human promyelocytic leukemic HL-60 cells. Treatment of HL-60 cells with gallic acid and epigallocatechin gallate (EGCG) resulted in the rapid decline of the intracellular concentration of putrescine, whereas that of spermidine and spermine was not significantly changed during the first 3 hours after treatments. Irradiation with UVB also selectively reduced the intracellular concentration of putrescine. On the other hand, cytotoxic concentrations of anticancer agents, such as etoposide and doxorubicin, only marginally reduced the intracellular concentration of putrescine during the first 3 hours. A significant decline of putrescine was observed at later stages when DNA fragmentation became more prominent. Three normal human cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and human tumor cell lines (squamous cell carcinoma, submandibular carcinoma, malignant malanoma, hepatoma), which showed higher resistance to apoptosis inducers, had significantly higher putrescine concentrations than HL-60 cells. These data suggest that the intracellular concentration of putrescine may be a useful marker for the apoptosis induction or the sensitivity of the cells to apoptosis inducers.
Seven Chinese medicines were investigated for their ability to modify nitric oxide (NO) production by unstimulated and lipopolysaccharide (LPS)-stimulated mouse macrophage-like Raw 264.7 cells, in comparison with their radical intensity and scavenging activity. LPS significantly stimulated the NO production by Raw 264.7 cells. Three Chinese medicines, Shosaiko-to, Hange-shashin-to and Sairei-to (tentatively classified as Group I), significantly reduced the extracellular concentration of NO in the LPS-stimulated cells, slightly below their cytotoxic concentrations. On the other hand, another four Chinese medicines, Byakko-ka-ninjin-to, Hochu-ekki-to, Juzen-taiho-to and Ninjin-yoei-to (tentatively classified as Group II), showed similar effects, but required higher concentrations due to the co-existence of both the inhibitors and stimulators for NO production by activated macrophages. Western blot analysis demonstrated that LPS stimulated the expression of inducible NO synthase (iNOS) at both protein and mRNA levels, and that Sairei-to reduced the LPS-induced iNOS expression more potently than did Juzen-taiho-to. ESR spectroscopy shows that Group I medicines generally produced higher amounts of radicals under alkaline condition, and scavenged superoxide (produced by hypoxanthine-xanthine oxidase reaction) and NO (produced by NOC-7, NO generator) more potently than Group II medicines. These data support the classification of Chinese medicines into two groups: Group I and Group II. The net inhibition of NO production by Group I medicines may be the summation of the radical scavenging activity and the inhibition of iNOS expression due to higher cytotoxicity. Group II medicines showed lower cytotoxicity, lower radical intensity, lower radical scavenging activity, but higher stimulation activity for NO production by macrophages than Group I, suggesting their possible application for immunopotentiation.
Rikko-san and its ingredients were investigated for their activity to modify nitric oxide (NO) production by unstimulated and lipopolysaccharide (LPS)-stimulated mouse macrophage-like Raw 264.7 cells. LPS significantly stimulated the NO production by Raw 264.7 cells, and Rikko-san effectively inhibited the stimulation effect of LPS even at non-cytotoxic concentrations. Among 5 Rikko-san ingredients, Kanzo showed a similar magnitude of inhibition of NO production. Shoma was also slightly inhibitory. On the other hand, Ryutan, Saishin and Bofu did not show such a clear-cut stimulation effect, due to the co-existence of both inhibitory and stimulatory substance(s) for NO production. Thus NO stimulators were present in Rikko-san and its four ingredients except for Kanzo. Western blot analysis demonstrated that LPS induced the production of inducible NO synthase (iNOS), and that non-cytotoxic concentrations of Rikko-san and Kanzo significantly inhibited the LPS-stimulated iNOS expression. ESR spectroscopy showed that Rikko-san, Kanzo, Shoma and Saishin, but not Ryutan and Bofu, produced radical(s) under alkaline condition. All samples scavenged superoxide (produced by hypoxanthine-xanthine oxidase reaction) and NO (produced by 1-hydroxy-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7)), possibly by their general reducing activity. These data suggest that the inhibition of NO production by Chinese medicines investigated here may be the result of both the inhibition of iNOS expression and their radical scavenging activity.