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Saori Tanaka,
Rina Tanaka,
Saeko Harada,
Yuka Kohda,
Hitoshi Matsumura,
Chikao Shimamoto,
Yukinori Sawabe,
Yoshinori Marunaka, Hiroko Kuwabara,
Yuko Takahashi,
Shigenori Ito,
Takashi Nakahari
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ABSTRACT: In antral mucous cells, acetylcholine (ACh, 1µM) activates Ca2+-regulated exocytosis, consisting of an initial peak that declines rapidly (initial transient phase) followed by a second slower decline (late phase) lasting during ACh stimulation. The addition of 8-bromo-cGMP (8BrcGMP) enhanced the initial phase, which was inhibited by a PKG inhibitor, guanosine 3', 5'-cyclic monophosphorothoiate, β-phenyl-1, N2-etheno-8-bromo-, Rp-isomer, sodium salt (Rp8BrPETcGMPS, 100 nM). However, Rp8BrPETcGMPS produced a delayed, but transient, increase in the exocytotic frequency during the late phase, which was abolished by a PKA inhibitor (PKI-amide), suggesting that Rp8BrPETcGMPS accumulates cAMP. The cGMP-dependent phosphodiesterase 2 (PDE2), which degrades cAMP, may exist in antral mucous cells. The PDE2 inhibitor, BAY-60-7550 (250 nM), mimicked the effect of Rp8BrPETcGMPS on ACh-stimulated exocytosis. Measurement of the cGMP and cAMP contents in antral mucosae revealed that ACh stimulates the accumulation of cGMP and that BAY-60-7550 accumulates cAMP similarly to Rp8BrPETcGMPS during ACh stimulation. Analyses of Western blot and immunohistochemistry demonstrated that PDE2A exists in antral mucous cells. In conclusion, Rp8BrPETcGMPS accumulates cAMP by inhibiting PDE2 in ACh-stimulated antral mucous cells, leading to the delayed, but transient, increase in the frequency of Ca2+-regulated exocytosis. PDE2 may prevent antral mucous cells from excessive mucin secretion caused by the cAMP accumulation.
AJP Gastrointestinal and Liver Physiology 02/2013; · 3.43 Impact Factor
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Indian Journal of Pathology and Microbiology 10/2012; 55(4):589-90. · 0.68 Impact Factor
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ABSTRACT: Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related pulmonary complication with rapidly progressing dyspnea, and occasionally induces sudden death. Here, we describe a postmortem-diagnosed PTTM case caused by gastric cancer, with the complaint of progressing dyspnea for 5 days.He did not have any abdominal symptoms or cancer history. PTTM should be considered in patients with rapidly worsening respiratory conditions, even if there is no cancer history.
Annals of thoracic medicine. 07/2012; 7(3):168-9.
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ABSTRACT: Invasive breast cancer is divided into luminal A, luminal B, HER2 overexpression, basal-like (BL) and normal-like subtypes, among which the BL subtype has the worst prognosis. The purpose of this study was to determine the clinicopathological and cytological characteristics of BL breast cancer (BLBC). Fine-needle aspiration cytology samples from 17 patients with consecutive BLBC were investigated, and the findings were compared with those of other subtypes (10 cases each) for the following cytomorphological features: necrosis; lymphocyte infiltration; mitotic index; apoptosis; naked nuclei; nuclear/cytoplasmic ratio; nuclear margin, size and pleomorphism; chromatin granularity and density; and nucleolar appearance. Histologically, the BLBCs were heterogeneous, and included medullary carcinoma and metaplastic carcinoma, in addition to invasive ductal carcinoma. Cytologically, high mitotic index, naked nuclei, and irregular nuclear margin were significantly observed when compared with both the luminal A and B subtypes. Large nuclei with nucleoli and lymphocyte infiltration were frequently seen compared with the luminal A and B subtypes, respectively. Squamous nodules were seen in all metaplastic cases, but not in the HER2 overexpression subtype. Lymphocyte infiltration, squamous metaplasia, and nuclear findings such as a high mitotic index, naked or large nuclei, an irregular nuclear margin and the presence of nucleoli, may be clues indicating BLBC. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.
Diagnostic Cytopathology 10/2011; · 1.16 Impact Factor
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ABSTRACT: Ciliary beat frequency (CBF) was measured in slice preparations of the Fallopian tube fimbria, using videomicroscopy with a high-speed (500 Hz) camera in guinea pigs that were treated with β-oestradiol benzoate (βE2B) and medroxy progesterone (mPRG). In non-ovulating guinea pigs at 4 weeks of age, the CBF of the fimbria was high (17.8 Hz). In sexually mature guinea pigs (12-16 weeks of age) with constant ovulation, the CBF varied from 12 Hz to 16 Hz. The in vivo administration of both ICI-182,780 (a blocker of βE2 receptors) and mifepristone (a blocker of PRG receptors) induced high CBF (17.4 Hz). The administration of βE2B at a low (3.2 mg/kg/day) or high (32 mg/kg/day) dose decreased the CBF to 14.5 Hz or 11 Hz, respectively. ICI-182,780 abolished the βE2B-induced changes in CBF and decreased CBF to 12 Hz. The administration of mPRG (6.4 mg/kg/day) decreased CBF to 12.5 Hz. Mifepristone abolished this mPRG-induced decrease in CBF and maintained the CBF at 15 Hz. However, administering both βE2B and mPRG increased CBF to 17.5 Hz, suggesting that βE2B inhibits mPRG actions and vice versa. To confirm the interactions between βE2B and mPRG, we administered both βE2B and mPRG to guinea pigs that were pretreated for 1.5 days with either mPRG (6.4 mg/kg/day) or βE2B (3.2 mg/kg/day). Prior treatment with βE2B or mPRG prevented the increase in CBF that was otherwise by βE2B plus mPRG, and maintained the CBF at 14.5 Hz or 13 Hz, respectively. The administration of βE2B plus mPRG still induced the expression of PRG receptors, indicating that the highest CBF is not the result of no expression of the receptors. In the beating cilia of the fimbria, the signals that are activated by the βE2 and PRG receptors are proposed to antagonize each other in regulating the frequency.
Biomedical Research 10/2011; 32(5):321-8. · 1.15 Impact Factor
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ABSTRACT: Cancers are supported by a distinct type of stroma, and versican is overexpressed in the stroma of malignant tumors, including breast cancer. Versican interacts with hyaluronan and fibrillin-1 at its amino terminus (G1) and carboxyl terminus (G3), respectively. Fibrillin-1 also associates with latent transforming growth factor-β binding protein (LTBP)-1 and -4. The detailed alteration of these molecules in breast cancer tissues is still unclear.
In 18 patients, alteration of versican, fibrillin-1 and LTBP-1 and 4 was elucidated in comparison with matched normal tissues, using real-time reverse transcriptase polymerase chain reaction, slot blotting and immunohistochemistry. The relationship between the protein expression and clinicopathological features was also investigated.
In breast cancer tissues, mRNAs for versican V1 and V0 were upregulated, and the extracted protein levels of the versican G1 and G3 domains were increased. Meanwhile, LTBP-4 was decreased, and fibrillin-1 and LTBP-1 remained unchanged. The immunohistochemical observations were consistent with the biochemical findings, and the molecules were localized in the stromal tissue rather than in the cancer cells themselves. The expression of versican G3 and G1 domains was positively related to the Ki67 index of carcinoma cells and tumor size, respectively.
The stromal alterations of versican and LTBP-4 might influence the carcinogenesis and progression of breast tumor cells and modulate their biological phenotypes.
Breast Cancer 04/2011; 19(1):46-53. · 1.36 Impact Factor
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Pathology International 04/2011; 61(4):262-3. · 1.62 Impact Factor
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ABSTRACT: Epithelioid hemangioendothelioma is a rare vascular neoplasm of low-grade malignancy. We observed a case of epithelioid hemangioendothelioma arising in a cervical lymph node. Fine needle aspiration cytology showed several characteristic findings of epithelioid hemangioendothelioma, that is, nuclear inclusion bodies, nuclear grooves, and amorphous material, in addition to physaliform chromatin pattern of a new clue. By reviewing the reports, the prevalence of these is clarified. Complex appearance of these findings is useful in the diagnosis.
Diagnostic Cytopathology 02/2011; 39(2):124-7. · 1.16 Impact Factor
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ABSTRACT: Epithelioid hemangioendothelioma is a rare vascular neoplasm of low-grade malignancy. We observed a case of epithelioid hemangioendothelioma arising in a cervical lymph node. Fine needle aspiration cytology showed several characteristic findings of epithelioid hemangioendothelioma, that is, nuclear inclusion bodies, nuclear grooves, and amorphous material, in addition to physaliform chromatin pattern of a new clue. By reviewing the reports, the prevalence of these is clarified. Complex appearance of these findings is useful in the diagnosis. Diagn. Cytopathol. 2011;39:124–127. © 2010 Wiley-Liss, Inc.
Diagnostic Cytopathology 01/2011; 39(2):124 - 127. · 1.16 Impact Factor
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Yukinori Sawabe,
Chikao Shimamoto,
Akiko Sakai, Hiroko Kuwabara,
Adel H Saad,
Takashi Nakano,
Kimitaka Takitani,
Hiroshi Tamai,
Hiroshi Mori,
Yoshinori Marunaka,
Takashi Nakahari
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ABSTRACT: Indomethacin (IDM, 10 microm), not aspirin (ASA; 10 microm), enhanced the Ca(2+)-regulated exocytosis stimulated by 1 microm acetylcholine (ACh) in guinea-pig antral mucous cells. Indomethacin inhibits prostaglandin G/H (PGG/H) and 15R-hydroperoxy-eicosatetraenoic acid (15R-HPETE) production from arachidonic acid (AA), while ASA inhibits PGG/H production but accelerates 15R-HPETE production. This suggests that IDM accumulates AA. Arachidonic acid (2 microm) enhanced Ca(2+)-regulated exocytosis in antral mucous cells to a similar extent to IDM. Moreover, a stable analogue of AA, arachidonyltrifluoromethyl ketone (AACOCF(3)), also enhanced Ca(2+)-regulated exocytosis, indicating that AA, not products from AA, enhances Ca(2+)-regulated exocytosis. We hypothesized that AA activates peroxisome proliferation activation receptor alpha (PPARalpha), because AA is a natural ligand for PPARalpha. A PPARalpha agonist (WY14643; 1 microm) enhanced Ca(2+)-regulated exocytosis, and a PPARalpha blocker (MK886; 50 microm) abolished the enhancement of Ca(2+)-regulated exocytosis induced by AA, IDM, AACOCF(3) and WY14643. Western blotting and immunohistochemical examinations demonstrated that PPARalpha exists in antral mucous cells. Moreover, MK886 decreased the frequency of Ca(2+)-regulated exocytosis activated by 1 microm ACh or 2 microm thapsigargin alone by 25-30%. Thus, ACh stimulates AA accumulation via an [Ca(2+)](i) increase, which activates PPARalpha, leading to enhancement of Ca(2+)-regulated exocytosis in antral mucous cells. A novel autocrine mechanism mediated via PPARalpha enhances Ca(2+)-regulated exocytosis in guinea-pig antral mucous cells.
Experimental physiology 08/2010; 95(8):858-68. · 3.17 Impact Factor
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Ayumi Nishimura,
Ko Sakuma,
Chikao Shimamoto,
Shigenori Ito,
Takashi Nakano,
Eriko Daikoku,
Masahide Ohmichi,
Takahisa Ushiroyama,
Minoru Ueki, Hiroko Kuwabara,
Hiroshi Mori,
Takashi Nakahari
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ABSTRACT: The ciliary beat frequency (CBF) of guinea-pig fimbria during the ovarian cycle was measured by video microscopy using a high-speed camera (500 Hz). In the follicular phase, with increasing concentrations of beta-oestradiol ([betaE(2)]) and a low concentration of progesterone ([PRG]), CBF increased from 13.5 to 16 Hz. In the ovulatory phase, with further increase of [betaE(2)], CBF decreased gradually from 16 to 13.5 Hz. In the early luteal phase, with low [PRG] and [betaE(2)], CBF increased to 17 Hz; however, in the middle luteal phase, with increasing [PRG], CBF decreased (12 Hz), and in the late luteal phase, with decreasing [PRG], CBF increased to 15 Hz. Then, in the resting phase, with low [betaE(2)] and [PRG], CBF decreased immediately to 14 Hz. The CBF of the fimbria was measured in guinea-pigs treated with beta-oestradiol benzoate (betaE(2)B) or medroxyprogesterone (mPRG). A low dose of betaE(2)B increased CBF to 14.5 Hz, whereas a high dose decreased it to 11 Hz. A betaE(2) receptor blocker, ICI-182,780, abolished the betaE(2)B-induced CBF changes and maintained CBF at 12.0 Hz. Medroxyprogesterone decreased CBF to 12.5 Hz, and mifepristone (a PRG receptor blocker) abolished the mPRG-induced CBF decrease and maintained CBF at 15 Hz. The addition of both blockers increased CBF to 18 Hz, suggesting that activation of betaE(2) or PRG receptors decreases the CBF of the fimbria. In conclusion, a moderate [betaE(2)] increase maintains a high CBF (15.5 Hz) in the follicular phase, and then further [betaE(2)] increase decreases CBF to 13.5 Hz in the ovulatory phase. In the early and late luteal phase, low [betaE(2)] and [PRG] increase CBF to 17 and 15 Hz, respectively, and in the middle luteal phase a high [PRG] decreases CBF (to 12 Hz). Thus, the CBF of the fimbria was controlled by signals via betaE(2) and PRG receptors in guinea-pigs.
Experimental physiology 04/2010; 95(7):819-28. · 3.17 Impact Factor
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ABSTRACT: A 73-year-old female, who suffered from rheumatoid arthritis for 10 years, developed precore mutant hepatitis B virus-associated fulminant hepatitis after 1 year of infliximab therapy and subsequent methotrexate withdrawal. We emphasize the importance of preemptive antiviral therapy before starting infliximab administration and withdrawing immunosuppressive drugs.
Clinical Rheumatology 04/2010; · 2.00 Impact Factor
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ABSTRACT: Electron microscopic examination of multicentric reticulohistiocytosis (MR) cells is reported. Most of the cells contained numerous dense bodies which seemed to be lysosomes. Complex interdigitations of the membranes of the adjacent MR cells were distinctive findings. Some of the cells contained myelinated dense bodies in the cytoplasm. Histochemically, the cells were strongly positive for acid phosphatase, alpha-naphthyl butyrate esterase and lysozyme. From these observations, the majority of MR cells appeared to be proliferations of monocyte/macrophage derived cells. In the synovium, these cells resembled type A synovial cells. Other smaller and fewer cells had many rough endoplasmic reticulum (RER), and these resembled type B synovial cells. In the synovium, MR cells might be formed by proliferation and fusion of synovial cells.
Pathology International 12/2008; 42(2):130 - 135. · 1.62 Impact Factor
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ABSTRACT: Dendritic cells within the dermis in the later stages of delayed-type contact hypersensitivity were examined ultra-structurally and immunohistochemically. The immunohis-tochemical observations were done using monoclonal antibody Ml 8, which reacts specifically with murine Langer-hans cells and interdigitating cells. Seventeen hours after challenge, infiltrating cells in the dermis included dendritic cells, possibly so-called indeterminate cells, monocytoid cells and Langerhans cells. Immunohistochemically, the indeterminate cells and some monocytoid cells were Ml 8 positive. These findings suggest that indeterminate cells are intimately related to Langerhans cells, and that they belong to the mononuclear phagocyte system. Ml-8 is a very useful marker for studies on the kinetics of Langerhans cells or indeterminate cells. Acta Pathol Jpn 41: 106 112, 1991.
Pathology International 12/2008; 41(2):106 - 112. · 1.62 Impact Factor
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ABSTRACT: OHK cells, a human lymphoma cell line, are known to produce large amounts of hyaluronan. We investigated the effect of 4-methylumbelliferone, an inhibitor of hyaluronan synthesis, on the activity of matrix metalloproteinases in OHK cells. Matrix metalloproteinase-9 was detected on gelatin zymography as the main metalloproteinase excreted into the medium of cultured OHK cells, and 4-methylumbelliferone added to the medium decreased the activity of the enzyme in a dose-dependent manner. Addition of Streptomyces hyaluronidase to the medium during cultivation did not decrease the enzyme activity. Reverse transcription-polymerase chain reaction revealed that 4-methylumbelliferone markedly decreased the level of mRNA for matrix metalloproteinase-9 in cultured OHK cells. A similar decrease of the activity of matrix metalloproteinase-9 by 4-methylumbelliferone was also observed in cultured human breast and colon carcinoma cells. These results suggest that 4-methylumbelliferone suppresses the expression of matrix metalloproteinase-9 in cultured cancer cells.
Cell Biology International 10/2007; 31(9):1022-6. · 1.48 Impact Factor
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ABSTRACT: Versican interacts with hyaluronan (HA) at its N-terminus and with fibrillin-1 at its C terminus. As versican in the dermis connects microfibrils to the HA-rich matrix for viscoelasticity, dermal diseases may involve destruction of these complexes. A recombinant versican protein, rVN, covering the HA binding region (HABR) of human versican and a polyclonal antibody, 6084, against rVN were prepared and characterized. Blotting analyses of skin extracts with 6084 and biotin-conjugated HA revealed that versican was a major HA-binding component in the dermis. Matrix metalloprotease-12, which is expressed in areas of solar elastosis, degraded versican and abrogated its HA-binding ability. Immunohistochemical analyses revealed that the elastic materials in solar elastosis lesions were negative for 6084, but positive for 2B1, an antibody recognizing the C-terminus of versican, indicating loss of the HABR in the aggregated elastic fibers. This loss of the HA-binding ability of versican followed by HA exclusion may be responsible for the pathological and phenotypical changes observed in solar elastosis.
Journal of Investigative Dermatology 08/2007; 127(7):1657-63. · 6.31 Impact Factor
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ABSTRACT: Gliosarcoma, a rare pathological entity composed of 2-8% malignant gliomas, is characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation. Here we report the preferential recurrence of a sarcomatous component in gliosarcoma after boron neutron capture therapy (BNCT), while a gliomatous component disappeared as a result of the treatment. A 56-year-old woman with a left frontal tumor was introduced to our clinic. After stereotactic biopsy, craniotomy was applied and 90% of the mass was resected. The histological diagnosis was glioblastoma with small amounts of sarcomatous component, that is, gliosarcoma. BNCT was applied 30 days after craniotomy. Two weeks after BNCT, almost all of the contrast-enhanced mass had disappeared on magnetic resonance images; however, a half year later, the mass recurred just below the original site and extended posteriorly. Irrespective of repetitive salvage surgeries, the patient died of the recurrent tumor. At autopsy, tumor cells of the frontal lobe were absent. A well-circumscribed mass of the parietal and occipital lobes was composed of sarcomatous material, with very little glial fibrillary acid protein-positive glial material. We found in this patient the preferential recurrence of the sarcomatous component of a gliosarcoma after potent radiotherapeutics in the form of BNCT.
Journal of Neuro-Oncology 02/2006; 76(2):143-7. · 3.21 Impact Factor
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ABSTRACT: A case of lipomatous pleomorphic adenoma in the ceruminous gland is reported. A 69-year-old Japanese woman presented with a mass in the posterior wall of the cartilaginous external auditory canal. Light microscopic examination revealed a well-circumscribed tumor composed of tubular structures with apocrine secretion and ceroid deposition, extensive mature adipocytes, and spindle-shaped myoepithelial cells in the myxoid and fibrous stroma. This case demonstrates the peculiar location of a lipomatous pleomorphic adenoma in the external auditory canal.
Pathology International 02/2006; 56(1):51-3. · 1.62 Impact Factor
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ABSTRACT: The receptor for hyaluronan mediated motility (RHAMM), which is a hyaluronan-binding protein, is a centrosomal and microtubal protein. Here, we have identified two RHAMM-binding proteins, glucose regulated protein (GRP) 78 and GRP75, using co-immunoprecipitation analysis. These two proteins directly bound to glutathione-S-transferase-RHAMM fusion proteins. By double immunostaining, GRP78 and GRP75 colocalized with RHAMM in interphase microtubules, but were separated in mitotic spindles. Prevention of microtubule polymerization by TN-16 and vincristine sulfate induced RHAMM overexpression without a significant change in GRP78/75. Taken together, GRP78/75 and RHAMM complexes may stabilize microtubules in the interphase, associated with a downregulation of RHAMM. These results reveal a new biochemical activity of RHAMM.
Biochemical and Biophysical Research Communications 02/2006; 339(3):971-6. · 2.48 Impact Factor
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ABSTRACT: The purpose of this study was to investigate whether orexin expression in the rat brain was changed during pregnancy. Brain samples were obtained from 5 nonpregnant rats and 10 pregnant rats (5; day 10 of gestation, and 5; day 20 of gestation). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed to investigate the expression of prepro-orexin mRNA and the housekeeping gene in the rat brain. The signals were quantified by the densitometric analysis. The distribution and expression of orexin-A and orexin-B were determined using immunohistochemistry. The ratio of the prepro-orexin mRNA expressions to the housekeeping gene expression in pregnant rat brain were significantly higher than that in nonpregnant control. There was no significant difference between prepro-orexin mRNA levels of day 10 and day 20 of gestation. Immunohistochemical staining for orexin-A and orexin-B was present in neurons within and around the lateral and posterior hypothalamic areas in both nonpregnant and pregnant rats. These results suggest that increased prepro-orexin mRNA levels at early gestational age in the maternal rat has a role on energy metabolism during pregnancy.
Neuroscience Letters 10/2004; 368(1):73-7. · 2.11 Impact Factor
