104 results on '"Kugai N"'
Search Results
2. The Parathyroid Hormone Receptor-Adenylate Cyclase System in Chicken Kidney
- Author
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Nissenson, R. A., Kugai, N., Arnaud, C. D., Massry, Shaul G., editor, Ritz, Eberhard, editor, and Jahn, Henri, editor
- Published
- 1980
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3. Parathyroid Hormone Receptors and Stimulation of Renal Cyclic 3′, 5′ Amp in vitro: Physiological Relevance?
- Author
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Kugai, N., primary, Dorantes, L., additional, Nissenson, R., additional, and Arnaud, C. D., additional
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- 1978
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4. A Case of Glycogen Storage Disease Type I Associated with an Incomplete Type of Fanconi Syndrome; The Protective Role of Lysosomal Alpha 1,4-Glucosidase and Insulin Deficiency Against Hypoglycemia
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Itakura, M., primary, Yamashita, N., additional, Fujita, T., additional, Koide, Y., additional, Kugai, N., additional, Yamamura, H., additional, and Yamashita, K., additional
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- 2008
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5. Important role of EP4, a subtype of prostaglandin (PG) E receptor, in osteoclast-like cell formation from mouse bone marrow cells induced by PGE2
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Ono, K, primary, Akatsu, T, additional, Murakami, T, additional, Nishikawa, M, additional, Yamamoto, M, additional, Kugai, N, additional, Motoyoshi, K, additional, and Nagata, N, additional
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- 1998
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6. Mouse Mammary Carcinoma Cell Line (BALB/c-MC) Stimulates Osteoclast Formation From Mouse Bone Marrow Cells Through Cell-to-Cell Contact
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Ono, K, primary, Akatsu, T, additional, Murakami, T, additional, Wada, S, additional, Nishikawa, M, additional, Kugai, N, additional, Yamamoto, M, additional, Matsuura, N, additional, and Nagata, N, additional
- Published
- 1998
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7. Bisphosphonates act on osteoblastic cells and inhibit osteoclast formation in mouse marrow cultures
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Nishikawa, M., primary, Akatsu, T., additional, Katayama, Y., additional, Yasutomo, Y., additional, Kado, S., additional, Kugai, N., additional, Yamamoto, M., additional, and Nagata, N., additional
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- 1996
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8. Relation between breastfeeding and the prevalence of asthma: the Tokorozawa Childhood Asthma and Pollinosis Study.
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Takemura Y, Sakurai Y, Honjo S, Kusakari A, Hara T, Gibo M, Tokimatsu A, and Kugai N
- Abstract
Many risk factors for asthma have been proposed including age, gender (male), smoking, and family history of asthma. The importance of breastfeeding to childhood asthma is a controversial issue. The present study investigated the relation between breastfeeding and the prevalence of asthma among a childhood population. The subjects were 25,767 students, representing all public elementary and junior high schools in Tokorozawa, Japan (age range, 6--15 years). The study population included 2,315 students with asthma and 21,513 controls. Participants' parents completed the Japanese version of the American Thoracic Society and Division of Lung Diseases, National Heart, Lung, and Blood Institute, questionnaire for children adopted by the Japanese Environmental Agency in 1998. The authors added supplementary questions on the parental history of asthma and feeding patterns from the age of 0--3 months. The risk of breastfeeding for asthma was compared with that of artificial feeding. After adjustment for age, gender, parental smoking status, and parental history of asthma, a significantly higher prevalence of asthma was noted among children who had been breastfed (adjusted odds ratio = 1.198; 95% confidence interval: 1.054, 1.363; p for trend < 0.01). The results indicated that breastfeeding in infancy might be related to the higher prevalence of asthma during preadolescence. [ABSTRACT FROM AUTHOR]
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- 2001
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9. Sources of Calcium Mobilized by α-Adrenergic Stimulation in Perfused Rat Liver.
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Kimura, S., Kugai, N., Tada, R., Kojima, I., Abe, K., and Ogata, E.
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- 1982
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10. Important role of EP4, a subtype of prostaglandin (PG) E receptor, in osteoclast-like cell formation from mouse bone marrow cells induced by PGE2.
- Author
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Ono, K., Akatsu, T., Murakami, T., Nishikawa, M., Yamamoto, M., Kugai, N., Motoyoshi, K., and Nagata, N.
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- 1998
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11. Microcomputer-aided insulin dose determination in intensified conventional insulin therapy.
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Shimauchi, T., Kugai, N., Nagata, N., and Takatani, O.
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- 1988
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12. Urinary type IV collagen as a marker for early diabetic nephropathy
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Kado, S., Aoki, A., Wada, S., Katayama, Y., Kugai, N., Yoshizawa, N., and Nagata, N.
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- 1996
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13. Relationship between Serum Free Thyroxine, Total Thyroxine and Thyroxine-Binding Globulin Concentrations in Patients with Graves' Disease.
- Author
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Bannai, C., Yamashita, K., Kugai, N., Koide, Y., and Akisada, M.
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- 1985
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14. A Case of Glycogen Storage Disease Type I Associated with an Incomplete Type of Fanconi Syndrome; The Protective Role of Lysosomal Alpha 1,4-Glucosidase and Insulin Deficiency Against Hypoglycemia.
- Author
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Itakura, M., Yamashita, N., Fujita, T., Koide, Y., Kugai, N., Yamamura, H., and Yamashita, K.
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- 1984
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15. ChemInform Abstract: REACTIONS OF 4-ACETOXY-2H-1,4-BENZTHIAZIN-3(4H)-ONE
- Author
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KUGAI, N., primary, HASHIMOTO, Y., additional, and SHUDO, K., additional
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- 1984
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16. Oxidative response to aldosterone of pyridine nucleotide in rat kidney in situ.
- Author
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Ogata, E, primary, Nishiki, K, additional, Kugai, N, additional, and Kishikawa, T, additional
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- 1977
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17. Comparison of bone SUV obtained from different SPECT/CT systems.
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Yoshimura M, Kugai N, Aida T, Hakamata D, Miyajima N, and Takahashi Y
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- Male, Humans, Retrospective Studies, Bone and Bones diagnostic imaging, Lumbar Vertebrae, Single Photon Emission Computed Tomography Computed Tomography, Prostatic Neoplasms
- Abstract
Objective: In bone scintigraphy, it is difficult to compare quantitative values, such as standardized uptake value (SUV), obtained from 2 different single-photon emission computed tomography combined with computed tomography (SPECT/CT) devices owing to differences of imaging acquisition and analysis methods. Therefore, the purpose of this study was to compare the SUV obtained from different SPECT/CT devices using the ratio to normal bone, and to analyze the correlation between them., Subjects and Methods: A total of 27 prostate cancer patients who underwent bone scintigraphy either using Symbia T16 or Symbia Intevo (Siemens Medical Solutions, Erlangen, Germany) were retrospectively analyzed. In each patient, spherical voxels of interest were placed on the following 5 reference points: humeral head (humerus), femoral neck (femur), lower part of the ilium (ilium), first lumbar vertebra (L1), fifth lumbar vertebra (L5), and the maximum SUV (SUV
max ) and average SUV (SUVave ) of these regions were measured., Results: The mean and variance of SUVave (humerus) was the smallest on both SPECT/CT. To compare the SUV obtained from the 2 devices, the SUVave ratio and SUVmax ratio of each region were calculated as the SUVave and SUVmax of each region divided by the SUVave of the humeral head in each patient. Median values of the SUVmax ratio and SUVave ratio of each region showed similar tendencies in both devices, with correlation coefficients between 0.93 and 1.19., Conclusion: Our results demonstrated that by expressing the quantitative value of SUVave of each region as a ratio to the SUVave of the humeral head, accumulation in the targeted bone can be compared even when the imaging acquisition and analysis methodsare different.- Published
- 2023
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18. Brachiocephalic to left brachial vein thrombotic vasculitis accompanying mediastinal pancreatic fistula: A case report.
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Kokubo R, Yunaiyama D, Tajima Y, Kugai N, Okubo M, Saito K, Tsuchiya T, and Itoi T
- Abstract
Background: Pancreatitis is a severe inflammatory pancreatic disease commonly due to bile duct stones or excessive alcohol usage, with clinical manifestations of abdominal pain, nausea, fever, and fluid collections. Healthy persons with less symptomatic pancreatitis are quite rare. Herein, we report a case of a patient with an undetermined onset of pancreatitis mimicking left arm cellulitis due to thrombotic vasculitis of the brachiocephalic vein., Case Summary: A 50-year-old woman visited our hospital for tenderness in the left arm over several recent days. She was diagnosed with cellulitis on the left arm due to left elbow tenderness. Intravenous antibiotics administration did not improve symptoms and laboratory data worsened; thus, chest and abdominal computed tomography (CT) was performed. CT demonstrated pancreatitis with pseudocyst around the pancreas extending to the mediastinum. Thrombotic vasculitis of the brachiocephalic to left brachial vein was observed, which could be the cause of left elbow pain. A pancreatic fistula was found in the head of the pancreas by endoscopic retrograde cholangiopancreatography, so a pancreatic cyst drainage tube via the duodenum was placed in the pseudocyst. Cyst content culture was positive for Escherichia coli infection. Clinical symptoms, imaging findings, and inflammatory reactions resolved gradually after starting therapeutic intervention. The mediastinal pancreatic pseudocysts shrunk, and the venous thrombi remained but shrunk., Conclusion: The case of a patient with pancreatitis with an undetermined onset that mimics left arm cellulitis is reported. Deep vein thrombosis should be kept in mind when treating patients with severe inflammatory disease., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2022
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19. Involvement of hepatocyte growth factor in the development of bone metastasis of a mouse mammary cancer cell line, BALB/c-MC.
- Author
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Ono K, Kamiya S, Akatsu T, Nakamura C, Li M, Amizuka N, Matsumoto K, Nakamura T, Kugai N, and Wada S
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- Animals, Animals, Newborn, Bone Marrow Cells cytology, Cell Culture Techniques, Cell Line, Tumor, Cell Proliferation drug effects, Cells, Cultured, Coculture Techniques, Culture Media chemistry, Dinoprostone pharmacology, Female, Hepatocyte Growth Factor metabolism, Mammary Neoplasms, Experimental drug therapy, Mice, Mice, Inbred BALB C, Mice, Inbred Strains, Neoplasm Invasiveness diagnostic imaging, Neoplasm Invasiveness pathology, Neoplasm Metastasis pathology, Neoplasm Metastasis prevention & control, Neoplasm Transplantation, Osteoblasts cytology, Pregnancy, Proto-Oncogene Proteins c-met metabolism, Skull cytology, Tibia diagnostic imaging, Tibia pathology, Tomography, X-Ray Computed, Hepatocyte Growth Factor antagonists & inhibitors, Hepatocyte Growth Factor pharmacology, Mammary Neoplasms, Experimental metabolism
- Abstract
Some cancers frequently affect the skeleton, and the bone microenvironment supports growth of certain cancer cells. After tumors metastasize to bone, they stimulate osteoclastogenesis and expand in the bone tissue. Hepatocyte growth factor (HGF), which was originally identified as a potent mitogen for hepatocytes, promotes tumor growth, invasion and metastasis. HGF is mainly produced by cells of mesenchymal origin, and osteoblasts/osteocytes and bone marrow stromal cells originate from mesenchymal cells. However, it is not clear what effect HGF has on tumor progression in bone metastasis. In the present study, we investigated the roles of HGF in bone metastasis using the mouse mammary cancer cell line BALB/c-MC. Cancer cells injected into hearts of mice metastasized to bone in their hind limbs. HGF immunoreactivity was detected in the stroma surrounding the tumor nests, and blood vessels expressing CD31 (a marker of endothelial cells) were observed in the HGF-positive area. To identify the cells producing HGF, we measured concentration of HGF in culture media. HGF concentration was elevated in osteoblast cultures (3.13+/-0.25 ng/ml), whereas HGF was undetectable (<0.4 ng/ml) in BALB/c-MC and bone marrow cell cultures. HGF concentration in osteoblast cultures increased 2.5-fold in response to 10(-6) M PGE(2). Addition of HGF to BALB/c-MC cultures caused doubling of the cell number. Moreover, Western blot analysis revealed expression of c-Met/HGF receptor by BALB/c-MC. In the Matrigel invasion chamber assay, addition of HGF to the bottom well increased the rate at which BALB/c-MC invaded the bottom well through the membrane. Furthermore, when osteoblasts were cultured in the bottom well, the number of BALB/c-MC cells that invaded the bottom well through the membrane increased 3.7-fold, compared to assays without osteoblasts. Addition of NK4, an inhibitor of HGF, completely abolished the enhancement of the invasive potential of the BALB/c-MC cells in the presence of osteoblasts. These findings suggest that HGF produced by osteoblasts induces migration of cancer cells from sinusoidal capillaries to bone marrow space and stimulates growth of cancer cells in the bone microenvironment. Thus, osteoblasts appear to promote bone metastasis of some cancers via HGF-c-Met signaling.
- Published
- 2006
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20. Biphasic effect of prostaglandin E2 on osteoclast formation in spleen cell cultures: role of the EP2 receptor.
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Ono K, Kaneko H, Choudhary S, Pilbeam CC, Lorenzo JA, Akatsu T, Kugai N, and Raisz LG
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- Animals, Bone Resorption, Carrier Proteins pharmacology, Cell Count, Cell Differentiation drug effects, Cells, Cultured, Female, Lymphocyte Depletion, Macrophage Colony-Stimulating Factor pharmacology, Membrane Glycoproteins pharmacology, Mice, Mice, Mutant Strains, Osteoclasts drug effects, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Receptors, Prostaglandin E agonists, Receptors, Prostaglandin E, EP2 Subtype, Receptors, Prostaglandin E, EP3 Subtype, Spleen drug effects, T-Lymphocytes physiology, Dinoprostone pharmacology, Osteoclasts cytology, Receptors, Prostaglandin E physiology, Spleen cytology
- Abstract
Unlabelled: We examined the effect of PGE2 on OC formation from spleen cells treated with M-CSF and RANKL. PGE2 decreased OC number at 5-6 days of culture and increased OC number, size, and resorptive activity at 7-8 days. A selective EP2 receptor agonist mimicked these effects. Deletion of the EP2 receptor or depletion of T-cells abrogated the increase in OC number., Introduction: Prostaglandin E2 (PGE2) has been reported to increase osteoclast (OC) number in spleen cells cultured with RANKL and macrophage-colony-stimulating factor (M-CSF). In this study, we examined the time course of PGE2 effects on spleen cells cultured with RANKL and M-CSF. We then investigated which PGE receptors and cell types were involved in these effects., Materials and Methods: Spleen cells were cultured from wildtype C57BL/6 mice and EP2 or EP4 receptor-deficient (-/-) and wildtype (+/+) mice on a mixed genetic background. Spleen cells were cultured with M-CSF and RANKL for 5-9 days with or without PGE2 or selective agonists for the four PGE2 receptors (EP1A, EP2A, EP3A, or EP4A). Some cultures were performed using T-cell-depleted spleen cells. OC number and size were quantitated. OC apoptosis and pit formation were measured at 7 or 8 days., Results: PGE2 decreased the number of OCs formed in the presence of RANKL and M-CSF at 5-6 days of culture and increased OC number at 8-9 days compared with cultures without PGE2. PGE2 also increased OC size at 7 and 8 days, decreased apoptosis of OC at 7 days, and increased pit formation at 8 days. EP1A or EP4A had no effect on OC. EP3A decreased OC number. EP2A mimicked effect of PGE2. EP2(-/-) spleen cells showed no increase in OC number in response to PGE2, whereas deletion of EP4 had no effect. Depletion of T-cells abrogated the late increase of OC number., Conclusions: We conclude that PGE2 has an initial inhibitory effect on OC formation in spleen cell cultures, possibly mediated by both EP2 and EP3 receptors, and a later stimulatory effect, mediated by the EP2 receptor, possibly acting on T-cells.
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- 2005
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21. The effect of deletion of cyclooxygenase-2, prostaglandin receptor EP2, or EP4 in bone marrow cells on osteoclasts induced by mouse mammary cancer cell lines.
- Author
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Ono K, Akatsu T, Kugai N, Pilbeam CC, and Raisz LG
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- Animals, Cell Line, Tumor, Coculture Techniques methods, Cyclooxygenase 2, Gene Deletion, Isoenzymes genetics, Male, Mammary Neoplasms, Animal genetics, Mammary Neoplasms, Animal metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Prostaglandin-Endoperoxide Synthases genetics, Receptors, Prostaglandin E genetics, Receptors, Prostaglandin E, EP2 Subtype, Receptors, Prostaglandin E, EP4 Subtype, Bone Marrow Cells metabolism, Isoenzymes deficiency, Osteoclasts metabolism, Prostaglandin-Endoperoxide Synthases deficiency, Receptors, Prostaglandin E deficiency
- Abstract
The inducible prostaglandin (PG) synthesis enzyme, cyclooxygenase-2 (COX-2), is involved in osteoclast (OC) formation in cocultures of mouse mammary cancer cell lines (MMT060562 or BALB/c-MC) and bone marrow cells through production of PGE(2). There are four PGE(2) receptors but only the EP2 and EP4 receptors are reported to be important for OC formation. We have investigated the role of COX-2, EP2 receptor, and EP4 receptor in marrow cells for osteoclastogenesis in cocultures of cancer cells and bone marrow cells. We cocultured cancer cell lines with bone marrow cells from COX-2 knockout (-/-), EP2 -/- or EP4 -/- mice compared to wild-type mice. In addition, an EP4 receptor antagonist (EP4 RA) was added in some cocultures. Disruption of COX-2 gene in bone marrow cells had no effect on PGE(2) production and OC formation in cocultures with MMT060562, while it abrogated PGE(2) production and OC formation in cocultures with BALB/c-MC. Disruption of the EP2 gene in bone marrow cells had no effect on OC formation in the cocultures, while disruption of the EP4 gene in bone marrow cells abrogated OC formation in the cocultures. Furthermore, EP4 RA suppressed OC formation and prevented the increase in receptor activator of nuclear factor kappaB ligand (RANKL) mRNA levels in the cocultures. We conclude that COX-2 in cancer cells is responsible for PGE(2) and OC production in cocultures with MMT060562, while COX-2 in bone marrow cells, not cancer cells, is responsible for PGE(2) and OC production in cocultures with BALB/c-MC, and EP4 receptors are essential for OC formation in both cocultures.
- Published
- 2003
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22. Involvement of cyclo-oxygenase-2 in osteoclast formation and bone destruction in bone metastasis of mammary carcinoma cell lines.
- Author
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Ono K, Akatsu T, Murakami T, Kitamura R, Yamamoto M, Shinomiya N, Rokutanda M, Sasaki T, Amizuka N, Ozawa H, Nagata N, and Kugai N
- Subjects
- Animals, Bone Neoplasms genetics, Bone Neoplasms pathology, Coculture Techniques, Cyclooxygenase 2, Dinoprostone biosynthesis, Female, Glycoproteins pharmacology, Isoenzymes genetics, Male, Mammary Neoplasms, Experimental genetics, Mice, Mice, Inbred BALB C, Osteoclasts drug effects, Osteolysis enzymology, Osteolysis etiology, Osteolysis pathology, Osteoprotegerin, Prostaglandin-Endoperoxide Synthases genetics, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Neoplasm genetics, RNA, Neoplasm metabolism, Receptors, Cytoplasmic and Nuclear, Receptors, Tumor Necrosis Factor, Tumor Cells, Cultured, Bone Neoplasms enzymology, Bone Neoplasms secondary, Isoenzymes metabolism, Mammary Neoplasms, Experimental enzymology, Mammary Neoplasms, Experimental pathology, Osteoclasts enzymology, Osteoclasts pathology, Prostaglandin-Endoperoxide Synthases metabolism
- Abstract
We previously reported that mouse mammary carcinoma cell lines (MMT060562 and BALB/c-MC) induced osteoclast formation through production of prostaglandin E2 (PGE2) in cocultures with mouse bone marrow cells, but the mechanism(s) of PG production remained unclear. In the present in vitro and in vivo studies, we tested the involvement of cyclo-oxygenase-2 (COX-2), an inducible rate-limiting enzyme in PG biosynthesis, in the stimulation of osteoclast formation by mouse mammary carcinoma cell lines. Addition of a selective COX-2 inhibitor, JTE-522, to cocultures of mammary carcinoma cell lines and bone marrow cells lowered PGE2 concentration in the culture media and inhibited osteoclast formation in a dose-dependent manner. Northern blotting showed a very high level of COX-2 messenger RNA (mRNA) expression in MMT060562. The mRNA expression was low in BALB/c-MC, but it increased when BALB/c-MC and bone marrow cells were cocultured. The results of immunocytochemistry for COX-2 protein in respective cultures were compatible with the results of COX-2 mRNA. In vivo, BALB/c-MC injected into the heart of Balb/c mice metastasized to bone and formed osteolytic lesions in their hindlimbs. Histological examination revealed that tumor cells had metastasized to the bone marrow cavity and destroyed the bone trabeculae. Immunohistochemistry demonstrated that bone marrow stromal cells adjacent to tumor cells expressed COX-2 protein. These findings suggest that COX-2 plays an important role in the osteolysis of bone metastasis in vivo as well as in osteoclast formation in cocultures used as an in vitro model of metastatic bone disease.
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- 2002
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23. The relationship between fish intake and the prevalence of asthma: the Tokorozawa childhood asthma and pollinosis study.
- Author
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Takemura Y, Sakurai Y, Honjo S, Tokimatsu A, Gibo M, Hara T, Kusakari A, and Kugai N
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- Adolescent, Child, Humans, Incidence, Japan epidemiology, Odds Ratio, Prevalence, Surveys and Questionnaires, Asthma epidemiology, Diet, Fish Products
- Abstract
Objective: The Japanese have a higher intake of fish and a lower incidence of asthma than occupants of western countries. The present epidemiological study investigated the relationship between dietary fish intake and the prevalence of asthma among a childhood population., Methods: Subjects represented all public elementary and junior high schools in Tokorozawa City in Japan (age range: 6-15 years old). The study population included 1,673 currently asthmatic students and 22,109 controls. Participants' parents completed the Japanese version of American Thoracic Society and Division of Lung Diseases, National Heart, Lung, and Blood Institute questionnaire for children, adopted by the Japan Environment Agency. We added supplementary questions (e.g., parental history of asthma and questions about frequency of foods eaten, including frequency of fish intake). Odds ratios for cases of current asthma according to frequency of fish intake were calculated, and a logistic regression analysis was used to adjust for possible confounding variables., Results: After adjustments for age, gender, parental history of asthma, and vegetables and fruits intake, a significantly higher prevalence of asthma was noted among subjects who ate fish one to two times a week than among those who ate fish one to two times a month (adjusted odds ratio: 1.117; 95% confidence interval: 1.005-1.241; P = 0.041). The risk increased gradually with increasing frequency of fish intake, and the positive trend was statistically significant., Conclusions: The results indicated that frequency of fish intake was positively related to the prevalence of asthma. This result might have important implications for health., (Copyright 2002 American Health Foundation and Elsevier Science (USA).)
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- 2002
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24. A cross-sectional study on the relationship between leisure or recreational physical activity and coronary risk factors.
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Takemura Y, Sakurai Y, Inaba Y, and Kugai N
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- Alcohol Drinking, Cross-Sectional Studies, Depression, Humans, Hypertrophy, Left Ventricular, Japan, Male, Middle Aged, Regression Analysis, Risk Factors, Smoking, Surveys and Questionnaires, Triglycerides metabolism, Coronary Disease etiology, Exercise
- Abstract
Several researchers have investigated the relationship between physical activity and coronary risk factors. Little is known about the strength of the relationship between physical activity and each coronary risk factor. The aim of this study is to determined the strength of the relationship between leisure or recreational physical activity and selected coronary risk factors. The subjects were 781 male Japanese office workers who underwent an annual physical examination in 1999, including interview about the type and frequency of their leisure or recreational physical activities, other lifestyle questionnaire, and biological measurement, calculated a physical activity index (PAI) for each subject. To investigate the strength of the relationship between PAI and each coronary risk factor, we carried out multiple regression analysis. Smoking habit, log triglycerides, self-rating depression scale (SDS) score, alcohol habit and left ventricular hypertrophy were significantly related to the physical activity (partial R2: 0.031, 0.018, 0.016, 0.0092, 0.0075, respectively). Smoking habit was the strongest determinant of the physical activity. Furthermore, we found the inverse relationship between SDS score and physical activity independently.
- Published
- 2000
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25. [Hepatitis associated with HIV].
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Nishiyama Y, Miura S, and Kugai N
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- Diagnosis, Differential, Humans, Prognosis, HIV Infections diagnosis, HIV Infections physiopathology, Hepatitis, Viral, Human diagnosis, Hepatitis, Viral, Human physiopathology
- Published
- 1999
26. Chinese hamster ovary cells expressing alpha4beta1 integrin stimulate osteoclast formation in vitro.
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Akatsu T, Ono K, Murakami T, Katayama Y, Nishikawa M, Wada S, Yamamoto M, Kugai N, Matsuura N, Takada Y, and Nagata N
- Subjects
- Acid Phosphatase analysis, Animals, Bone Development drug effects, Bone Marrow Cells drug effects, Bone Neoplasms, Calcitriol pharmacology, Cell Line, Transformed, Coculture Techniques, Cricetinae, Dinoprostone pharmacology, Immunohistochemistry, Integrin alpha4beta1, Interleukin-6 pharmacology, Isoenzymes analysis, Male, Mice, Spleen cytology, Spleen drug effects, Tartrate-Resistant Acid Phosphatase, CHO Cells metabolism, Cell Communication drug effects, Integrins analysis, Osteoclasts drug effects, Receptors, Lymphocyte Homing analysis, Vascular Cell Adhesion Molecule-1 analysis
- Abstract
It is reported that Chinese hamster ovary cells transfected with human alpha4 cDNA (alpha4CHOs) and expressing functional alpha4beta1 integrin developed bone metasasis in nude mice. To clarify the role of alpha4beta1 integrin in bone metastasis, in terms of tumor-mediated bone destruction, we examined whether alpha4CHOs stimulate osteoclast formation in cocultures with mouse bone marrow cells. The number of osteoclast-like cells identified as tartrate-resistant acid phosphatase positive multinucleated cells (TRAP(+) MNCs) formed from bone marrow cells increased with the increasing number of alpha4CHOs cocultured. The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and prostaglandin E2 (PGE2) on TRAP(+) MNC formation were enhanced in cocultures with alpha4CHOs. TRAP(+) MNCs induced by alpha4CHOs possessed calcitonin receptors and resorbed calcified tissues. In cocultures, alpha4CHOs and bone marrow stromal cells were in contact with each other and bone marrow stromal cells expressed vascular cell adhesion molecule-1 (VCAM-1), which is one of the ligands for alpha4beta1 integrin. TRAP(+) MNC formation was not stimulated in cocultures where direct contact between alpha4CHOs and bone marrow cells was inhibited by membrane filters. Alpha4CHOs do not support TRAP(+) MNC formation in cocultures with spleen cells but do support TRAP(+) mononuclear cell and MNC formation from spleen cells in the presence of osteoblastic cells. Cultured media from alpha4CHOs, bone marrow cells, and cocultures of alpha4CHOs and bone marrow cells did not stimulate TRAP(+) MNC formation or enhance the effects of 1,25(OH)2D3 and PGE2 in bone marrow cultures. The concentrations of PGE2 and interleukin-6 (IL-6) in cultured media were not different between the cultures of bone marrow cells and the cocultures of bone marrow cells and alpha4CHOs. Anti-human alpha4 and anti-mouse VCAM-1 antibodies inhibited TRAP(+) MNC formation induced by alpha4CHOs. These results indicate that alpha4CHOs stimulated TRAP(+) MNC formation through direct cell-to-cell interaction between alpha4beta1 and VCAM-1. It is suggested that in addition to various soluble factors regulating osteoclast formation, cell-to-cell interaction between tumor cells and bone marrow cells is important for inducing osteoclasts at the site of bone metastasis and leading to bone destruction.
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- 1998
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27. A third-generation bisphosphonate, YM175, inhibits osteoclast formation in murine cocultures by inhibiting proliferation of precursor cells via supporting cell-dependent mechanisms.
- Author
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Nishikawa M, Yamamoto M, Murakami T, Akatsu T, Kugai N, and Nagata N
- Subjects
- Animals, Bone Marrow Cells drug effects, Cell Division drug effects, Cell Fusion, Coculture Techniques, Culture Media, Dose-Response Relationship, Drug, Giant Cells drug effects, Methylcellulose, Mice, Spleen drug effects, Stromal Cells drug effects, Anti-Inflammatory Agents pharmacology, Dexamethasone pharmacology, Diphosphonates pharmacology, Osteoblasts drug effects, Osteoclasts drug effects
- Abstract
The theory that bisphosphonates inhibit osteoclast formation through their effects on osteoblastic cells remains controversial. To confirm the inhibitory effect of bisphosphonates on osteoclast formation and gain some insights into the underlying mechanisms, we examined the effect of disodium dihydrogen (cycloheptylamino)-methylene-bisphosphonate monohydrate (YM175) on osteoclast-like multinucleated cell (OCL) formation in various mouse coculture systems. When different origins of osteoclast precursors (bone marrow, spleen, or nonspecific esterase-positive cells) were cocultured with the same supporting cells (calvarial osteoblasts), YM175 inhibited OCL formation similarly in all cultures. When the same osteoclast precursors (spleen cells) were cocultured with supporting cells of different origin, the results were variable. YM175 inhibited OCL formation almost completely in cocultures with calvarial osteoblasts or osteoblastic cell line KS4, while it did not, or only slightly, inhibit OCL formation in cocultures with stromal cell lines, ST2 or MC3T3-G2/PA6. Temporal addition of YM175 in cocultures of spleen cells with osteoblastic cells revealed that YM175 was effective when it was present at an early phase of the culture period. Consistent with this observation, YM175 in the presence of osteoblastic cells inhibited proliferation of preosteoclastic cells, but did not inhibit the fusion of mononuclear prefusion osteoclasts. In conclusion, the inhibitory effect of YM175 on OCL formation was confirmed in various murine coculture systems, but the effect was dependent on the types of bone-derived cells supporting osteoclastogenesis. The findings suggest that YM175 inhibits osteoclastogenesis by inhibiting the proliferation of osteoclast precursors through its action on supporting cells of osteoblast lineage rather than acting directly on osteoclast precursors.
- Published
- 1998
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28. The mouse mammary tumor cell line, MMT060562, produces prostaglandin E2 and leukemia inhibitory factor and supports osteoclast formation in vitro via a stromal cell-dependent pathway.
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Akatsu T, Ono K, Katayama Y, Tamura T, Nishikawa M, Kugai N, Yamamoto M, and Nagata N
- Subjects
- Acid Phosphatase analysis, Alkaline Phosphatase analysis, Animals, Biomarkers, Tumor analysis, Calcitonin analysis, Coculture Techniques, Isoenzymes analysis, Leukemia Inhibitory Factor, Male, Mammary Neoplasms, Experimental, Mice, Mice, Inbred BALB C, Stromal Cells cytology, Tartrate-Resistant Acid Phosphatase, Tumor Cells, Cultured, Bone Marrow Cells cytology, Bone Resorption metabolism, Growth Inhibitors biosynthesis, Interleukin-6, Lymphokines biosynthesis, Osteoclasts cytology, Prostaglandins E biosynthesis
- Abstract
Osteoclastic bone resorption increases at the site of bone metastasis, but little is known about how tumor cells induce osteoclast (OC) recruitment in the bone marrow microenvironment. To clarify this point, we examined the effects of various mouse tumor cells on OC recruitment using cocultures of tumor cells and mouse marrow cells. The mouse mammary tumor cell lines, MMT060562 (MMT), BALB/c-MC, Jyg-MC(A), or other nonmammary tumor cell lines, LLC and B16, were cocultured with mouse marrow cells, and OC recruitment from marrow cells was determined by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells (TRAP(+) MNCs) formed. Of the tumor cells examined, MMT and BALB/c-MC stimulated OC formation, but other tumor cells did not. OC formation with MMT was dependent on the number of MMTs inoculated, and only ten cells per well were sufficient to induce OC development. OCs appeared on day 4, and the number reached a maximum on days 5-8 and decreased thereafter. TRAP(+) MNCs induced by MMT satisfied the major criteria of OCs, such as the presence of calcitonin receptors and the ability to resorb calcified tissues. The majority of OCs were formed adjacent to the stromal cells, which were positive for alkaline phosphatase. When spleen cells were cocultured with MMT, no OCs were formed. In contrast, when osteoblastic cells were added to cocultures of spleen cells and MMT, many OCs were formed. The cultured media (CM) of MMT induced OC formation in mouse marrow cultures. Neither parathyroid hormone-like nor interleukin 1-like activity was present in the CM. MMT constitutively produced prostaglandin E2 (PGE2) and OC formation in cocultures was completely inhibited by indomethacin. Fractionation of the CM of MMT by ultrafiltration indicated that the OC-inducing activities were present not only in the fraction with molecular weight below 3 kDa but also in the fraction with molecular weight above 3 kDa. OC-inducing activity with high molecular weight was eluted around 50 kDa by Bio-Gel P-60 column chromatography. The active fractions also possessed leukemia inhibitory factor (LIF) activity, and OC-inducing activity of the peak fraction was inhibited in the presence of anti-LIF neutralizing antibody. The results of this study indicated that MMTs release PGE2 and LIF, which in turn stimulate OC formation via a stromal cell-dependent pathway. These culture systems will help to clarify the mechanisms by which tumor cells induce OC formation in a bone marrow microenvironment.
- Published
- 1998
- Full Text
- View/download PDF
29. Lack of association between the Trp64 Arg mutation in the beta 3-adrenergic receptor gene and obesity in Japanese men: a longitudinal analysis.
- Author
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Nagase T, Aoki A, Yamamoto M, Yasuda H, Kado S, Nishikawa M, Kugai N, Akatsu T, and Nagata N
- Subjects
- Adult, Body Mass Index, Body Weight, Diabetes Mellitus, Type 2 genetics, Gene Frequency, Heterozygote, Homozygote, Humans, Japan, Longitudinal Studies, Male, Middle Aged, Reference Values, Mutation, Obesity genetics, Receptors, Adrenergic, beta genetics
- Abstract
The beta 3-adrenergic receptor (beta 3AR) is implicated in the regulation of thermogenesis and lipolysis, and it is suggested that the Trp64 Arg mutation in this receptor may contribute to the development of obesity. To examine whether the Trp64 Arg mutation had any effect on body weight during adult life, the beta 3AR genotype was determined in 186 unselected Japanese men, most of whom had records of body weight measured yearly from 25-53 yr of age. Of them, 26 subjects were diagnosed as having noninsulin-dependent diabetes mellitus (NIDDM) and 41 as having impaired glucose tolerance. There were 6 subjects (3%) with homozygous mutation, 67 (36%) with heterozygous mutation, and 113 (61%) with normal allele. Among the 3 genotypes, there were no significant differences in body mass index (BMI) at any age between 25-53 yr and the prevalence of NIDDM at the age of 53 yr. When longitudinal changes in body weight were compared between subjects with and without mutation, the former were less prone to gain weight than the latter. The frequency of the mutant allele was 1) not different among obese (BMI, > 26.4), intermediate (BMI, 22-26.4), and nonobese (BMI, < 22.0) subjects (0.21, 0.22, and 0.26, respectively; P = 0.77); 2) lower in subjects with NIDDM than in those without it, but the difference was insignificant (0.12 vs. 0.23; P = 0.07); and 3) similar between 186 unselected men and another group of 100 patients with NIDDM that were randomly selected for comparison (0.21 vs. 0.23). These results suggest that the beta 3AR is not a major contributing factor to obesity or NIDDM in Japanese men.
- Published
- 1997
- Full Text
- View/download PDF
30. Role of nonenzymatic glycosylation of type I collagen in diabetic osteopenia.
- Author
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Katayama Y, Akatsu T, Yamamoto M, Kugai N, and Nagata N
- Subjects
- Animals, Blood Glucose metabolism, Body Weight physiology, Bone Density physiology, Bone Diseases, Metabolic etiology, Cells, Cultured, Diabetes Mellitus, Experimental complications, Extracellular Matrix metabolism, Glycosylation, Male, Rats, Rats, Sprague-Dawley, Bone Diseases, Metabolic metabolism, Bone and Bones metabolism, Collagen metabolism, Diabetes Mellitus, Experimental metabolism, Osteoblasts physiology
- Abstract
Formation of advanced glycation end products (AGEs) in extracellular matrix (ECM) is implicated in the development of chronic diabetic complications. However, the involvement of AGEs in diabetic bone disease has not been well established. We have examined whether AGEs are increased in the bone collagen of streptozotocin-induced diabetic rats in vivo and whether glycation of type I collagen affects the functions of osteoblastic cells in vitro. During 12 weeks of observation, AGEs in collagen extracted from the tibiae of diabetic rats increased in a time-dependent manner and were significantly higher than controls at every time point. In vitro, the incubation of collagen with glucose-6-phosphate resulted in a time-dependent increase of AGEs. When osteoblastic cells isolated from fetal rat calvaria were cultured on AGE-modified type I collagen, it dose-dependently inhibited phenotypic expressions of osteoblasts. Among osteoblastic parameters, nodule formation was the most sensitive, being inhibited by approximately 70% by the glycation of collagen for only 1 week. Alkaline phosphatase activity and osteocalcin secretion were inhibited by 20-30% and 15-70%, respectively, by the glycation of collagen for 1-5 weeks. These results indicate that AGE-modified collagen affects osteoblastic cell differentiation and function in vitro and suggest that similar changes occurring in vivo may contribute to diabetic osteopenia.
- Published
- 1996
- Full Text
- View/download PDF
31. The results of the "essential laboratory tests" applied to new outpatients--re-evaluation of diagnostic efficiencies of the test items.
- Author
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Takemura Y, Kobayashi H, Kugai N, and Sekiguchi S
- Subjects
- Adolescent, Aged, Aged, 80 and over, Child, Humans, Middle Aged, Clinical Laboratory Techniques, Outpatients
- Abstract
We have analyzed diagnostic efficiencies of the individual "Essential laboratory test" items when these tests were applied to 520 new outpatients in the division of comprehensive medicine in a teaching hospital. The integration of these test results with history-taking and physical examination resulted in 544 primary clinical diagnoses which corresponded to the patient's illness complained and in 361 additional diagnoses unrelated to their chief complaints but found by chance by the addition of the test results. Clinical usefulness of these test items were variable depending on the disease category, demonstrating a superior diagnostic efficiency in infectious or inflammatory diseases, liver and biliary tract diseases, hematological disorders or metabolic diseases such as hyperlipidemia and diabetes mellitus, but a lesser degree of usefulness in gastro-intestinal or neurogenic diseases. Urine urobilinogen could not establish its clinical usefulness because of extremely low diagnostic sensitivity even in liver diseases. The leukocyte differential count provided confirmatory information for infectious or inflammatory diseases and was helpful for the estimation of the etiologic nature of infectious diseases. This study failed to terminate a controversy for the adoption of sialic acid instead of erythrocyte sedimentation rate (ESR) in the "Essential laboratory test" items, since the former test showed lower sensitivity, even though higher specificity, in infectious or inflammatory status than ESR. Low albumin globulin ratio (A/G) revealed equivalent diagnostic sensitivity and specificity to the elevated levels in alpha 1 and/or alpha 2 globulin fractions in infectious or inflammatory status, being helpful for the evaluation of patient's general condition at a glance. Incidental analysis for diagnostic values of cholinesterase and random blood glucose for the detection of fatty liver and diabetes mellitus, respectively, suggested that these two tests may be included in the "Essential laboratory tests". Simultaneous measurement of serum creatinine and blood urea nitrogen levels was recommended for the ambulatory screening of renal insufficiency, rather than the measurement either alone. The results in this study provide scientific bases on the usefulness of the individual test items and should be taken into account in the next version of the "Essential laboratory tests".
- Published
- 1996
32. Magnetic resonance imaging of multiple brain abscesses of the bilateral basal ganglia.
- Author
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Nagase T, Wada S, Nakamura R, Morisako T, Kamakura K, Kugai N, Yamamoto M, Tsuchiya K, and Nagata N
- Subjects
- Basal Ganglia, Brain Abscess complications, Female, Humans, Klebsiella Infections complications, Klebsiella pneumoniae, Middle Aged, Sepsis complications, Brain Abscess diagnosis, Magnetic Resonance Imaging
- Abstract
A 64-year-old woman developed multiple brain abscesses of the basal ganglia associated with Klebsiella pneumoniae septicemia. Magnetic resonance (MR) images showed three different stages of the brain abscesses. The images of early cerebritis of this site mimicked lacunar infarctions or dilated Virchow-Robin spaces. The differentiation of the brain abscess from lacunae and dilated Virchow-Robin spaces is discussed, together with the evolution of the brain abscesses on MR images.
- Published
- 1995
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33. Non-cushingoid Cushing's syndrome due to adrenocorticotropic hormone-independent bilateral adrenocortical macronodular hyperplasia.
- Author
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Nemoto Y, Aoki A, Katayama Y, Kado S, Yasutomo Y, Kugai N, Yamamoto M, Terahata S, and Nagata N
- Subjects
- Adrenal Glands metabolism, Aged, Cushing Syndrome diagnosis, Cushing Syndrome metabolism, Cushing Syndrome therapy, Humans, Hyperplasia complications, Male, Adrenal Glands pathology, Adrenocorticotropic Hormone blood, Cushing Syndrome etiology
- Abstract
This case report describes a 68-year-old man with Cushing's syndrome due to adrenocorticotropic hormone (ACTH)-independent bilateral adrenocortical macronodular hyperplasia (AIMAH). He was referred to our hospital for evaluation of bilateral enlargement of the adrenal glands found incidentally by computed tomography (CT). He had a ten-year history of hypertension. Although he was normokalemic and did not show Cushingoid features, the diagnosis of ACTH-independent Cushing's syndrome was established by endocrinological examinations. His plasma cortisol showed no diurnal rhythm and was unsuppressible by high-dose (8 mg/day) dexamethasone. Plasma ACTH was undetectable and did not respond to corticotropin-releasing hormone. Excised adrenal glands were markedly enlarged (right 28 g and left 64 g). Macroscopic appearance of the glands showed multiple yellowish nodules typical for AIMAH; microscopic findings were also compatible with AIMAH. The present case indicates that patients with AIMAH sometimes do not show typical Cushingoid features and therefore AIMAH can be found incidentally from ultrasound or CT examination of the abdomen.
- Published
- 1995
- Full Text
- View/download PDF
34. [Application of inflammation markers in the "essential laboratory tests" to new outpatients and analysis for the efficacious selection of these items].
- Author
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Takemura Y, Matsuta H, Kugai N, and Sekiguchi S
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Blood Sedimentation, C-Reactive Protein analysis, Child, Female, Humans, Male, Middle Aged, N-Acetylneuraminic Acid, Sialic Acids blood, Ambulatory Care, Biomarkers blood, Diagnostic Tests, Routine, Inflammation diagnosis
- Abstract
We have re-evaluated the usefulness of the inflammation markers in the "essential laboratory tests" advocated by Japan Society of Clinical Pathology and analyzed for efficacious selection of these items by applying these tests to 349 new outpatients visited Comprehensive Medicine, National Defense Medical College. Among the patients with "tentative initial diagnoses" of infectious or inflammation-related diseases (133 cases), the diagnoses were confirmed in 102 patients by positive inflammation marker(s), whereas additional 22 cases with the diagnoses other than inflammation-related diseases were found to be in the inflammatory status by these tests. Elevated C-reactive protein (CRP) levels were not correlated with the leukocyte number, however, neutrophilia (neutro. > 70%) and/or left shift of the neutrophils (stab > 15%) were demonstrated in approximately 50% of the patients with elevated serum CRP levels. Increases of serum sialic acid highly accompanied with increases of CRP, alpha 1 or alpha 2 fraction of serum protein and elevation of erythrocyte sedimentation rate (ESR), indicating that serum sialic acid levels reflected more strictly inflammatory status than ESR. There is a relatively good correlation (r = 0.813) between serum sialic acid values and the total amounts of alpha 1 and alpha 2 protein fraction, while poor correlations were shown between CRP and sialic acid values (r = 0.606), or ESR and sialic acid values (r = 0.671). These results indicate that (1) simultaneous measurements of CRP, leukocyte number and leukocyte differential fraction are useful for the confirmation of early stage of inflammation and evaluation of the nature of infectious diseases; (2) measurement of serum sialic acid levels is more desirable for the evaluation of inflammatory status than ESR; and (3) serum protein profile can be substituted by sialic acid for the evaluation of acute inflammatory status alone.
- Published
- 1994
35. A case of 17 alpha-hydroxylase deficiency with retained menstruation.
- Author
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Katayama Y, Kado S, Wada S, Nemoto Y, Kugai N, Furuya K, and Nagata N
- Subjects
- Adult, Chorionic Gonadotropin pharmacology, Estradiol blood, Female, Follicle Stimulating Hormone blood, Gonadotropin-Releasing Hormone pharmacology, Humans, Luteinizing Hormone blood, Menstruation Disturbances blood, Adrenal Hyperplasia, Congenital blood, Adrenal Hyperplasia, Congenital enzymology, Menstruation Disturbances enzymology
- Abstract
A patient with 17 alpha-hydroxylase deficiency (17OHD) who continued to menstruate is reported. A 24-year-old woman who presented with hypertension, hypokalemia and irregular menses had increased plasma ACTH and mineralocorticoids without any increase in glucocorticoids or sex steroids, and a bilateral adrenal enlargement on abdominal X-ray CT. ACTH stimulation test revealed hyperresponse of the metabolites of the mineralocorticoid pathway and blunted or absent response of those of the glucocorticoid and androgen pathway. Almost all of the abnormalities disappeared after dexamethasone administration. While 17OHD is usually known to accompany hypergonadotropic hypogonadism, the patient continued to menstruate, though irregularly. Although human chorionic gonadotropin administration failed to induce response, basal plasma levels of ovarian steroid (estradiol) and gonadotropins as well as response to LHRH stimulation test were all normal. Thus, the clinical and biochemical features of this case is compatible with the partial deficiency of both adrenals and ovaries, being less severe in the latter. A further analysis especially at molecular level is needed to elucidate the basis for the heterogeneity of this disorder.
- Published
- 1994
- Full Text
- View/download PDF
36. Changes of bone metabolic markers in patients with bone metastases: clinical significance in assessing bone response to chemotherapy.
- Author
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Wada S, Katayama Y, Yasutomo Y, Kugai N, and Nagata N
- Subjects
- Adult, Aged, Alkaline Phosphatase blood, Amino Acids urine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Neoplasms drug therapy, Bone Resorption metabolism, Female, Humans, Hydroxyproline urine, Male, Middle Aged, Osteocalcin blood, Osteogenesis physiology, Prognosis, Biomarkers, Tumor metabolism, Bone Neoplasms metabolism, Bone Neoplasms secondary, Bone and Bones metabolism
- Abstract
To determine the changes in bone metabolism in response to combined chemotherapy in patients with bone metastases (BM), we examined osteocalcin (BGP), alkaline-phosphatase (ALP), hydroxyproline (HYP), pyridinoline (PYR), and/or deoxypyridinoline (D-PYR) in 25 cancer patients. In patients without BM, serum BGP was normal and not affected by chemotherapy. In patients with BM, however, BGP was often abnormally high or low, and some patients reacted to chemotherapy with a BGP increase at 4 weeks after initiation of therapy. Such an increase was observed in the group of patients who responded favorably to therapy as judged by a decrease in bone pain and tumor-associated biochemical markers. Urine HYP, PYR, and D-PYR were high in patients with BM before therapy; D-PYR decreased transiently at 2 weeks and increased thereafter. We assume that increased bone-resorption markers along with increased bone formation markers after therapy would indicate recovery of coupled bone metabolism, as the deranged bone remodeling is improved by tumor-regression. This study suggests that BGP and D-PYR can be useful early markers to predict favorable bone response to chemotherapy in patients with BM.
- Published
- 1993
- Full Text
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37. Thyroid dysfunction in isolated adrenocorticotropic hormone (ACTH) deficiency: case report and literature review.
- Author
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Murakami T, Wada S, Katayama Y, Nemoto Y, Kugai N, and Nagata N
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Autoimmune Diseases etiology, Autoimmune Diseases physiopathology, Female, Humans, Hypothyroidism etiology, Hypothyroidism physiopathology, Japan, Male, Middle Aged, Pituitary Gland physiopathology, Thyrotropin metabolism, Adrenocorticotropic Hormone deficiency, Thyroid Gland physiopathology
- Abstract
A case of isolated ACTH deficiency accompanying transient primary hypothyroidism was reported along with a review of literature on isolated ACTH deficiency in Japan with special reference to its association with thyroid function. Our case, a 56-year-old woman, developed somnolence and hypoglycemia due to isolated ACTH deficiency. She also had the features of hypothyroidism, namely mounding phenomenon, muscle rigidity, increased plasma myogenic enzymes and cold intolerance. Both free T3 and free T4 were decreased, and basal as well as TRH-stimulated TSH levels were abnormally high. Plasma thyroglobulin was increased and no anti-thyroid antibodies were detected. All thyroid related physical and biochemical abnormalities disappeared after hydrocortisone replacement. A review of the literature on 103 cases disclosed that more than half the cases with isolated ACTH deficiency had a high plasma level of TSH, basal and/or TRH-induced, while the antithyroid antibodies were reported to be positive in only 13 cases. In more than 70% of such cases, the abnormality in the pituitary-thyroid axis was transient and was reversed by glucocorticoid replacement. Our case and cases in the literature indicate that the interference of thyroid hormone synthesis and/or secretion by glucocorticoid deficiency per se is the major cause of thyroid dysfunction rather than associated autoimmune thyroid disease.
- Published
- 1993
- Full Text
- View/download PDF
38. [Laboratory tests in primary care medicine: pre-clinical, ambulatory screening test system on the basis of the patient's chief complaints in the initial diagnosis making].
- Author
-
Hayashi K, Takemura Y, Hanba Y, Mori S, Kugai N, and Sekiguchi S
- Subjects
- Adolescent, Adult, Aged, Child, Female, Humans, Male, Mass Screening, Medical History Taking, Middle Aged, Clinical Laboratory Techniques, Diagnostic Tests, Routine, Primary Health Care
- Abstract
We have explored the efficacious laboratory test system to be performed before the first medical contact with a physician on the basis of the patient's chief complaints and their abnormalities of the "essential laboratory tests" advocated by the Japan Society of Clinical Pathology by analyzing 2,625 complaints from 2,175 new patients visited the outpatient unit of Comprehensive Medicine, National Defense Medical College. The patients with complaints such as general fatigue, fever of unknown origin or reno-urinary symptoms showed higher abnormalities of these diagnostic tests than those in 750 patients performed these tests irrespective of the patient's chief complaints. However, complaints originated from neurological, gastro-intestinal, cardiovascular or respiratory diseases were not associated with abnormalities of these laboratory tests in the patients as compared to those in 750 patients mentioned above. These results indicate that (1) clinical usefulness of the "essential laboratory tests" are variable depending on the patients chief complaints and these tests are recommended for the patients with complaints such as general fatigue, fever of unknown origin or reno-urinary symptoms as pre-clinical ambulatory screening tests before history taking and physical examination to enable to make accurate initial diagnosis and subsequent efficacious medical approach and (2) test items should be selected depending on the patient's chief complaints.
- Published
- 1993
39. Parathyroid hormone-related protein as a cause of hypercalcemia in a B-cell type malignant lymphoma.
- Author
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Wada S, Kitamura H, Matsuura Y, Katayama Y, Ohkawa H, Kugai N, Motoyoshi K, Fuse Y, and Nagata N
- Subjects
- Aclarubicin therapeutic use, Adult, Alkaline Phosphatase blood, Antineoplastic Combined Chemotherapy Protocols, Calcitriol blood, Cisplatin therapeutic use, Creatinine blood, Cyclic AMP blood, Cytarabine analogs & derivatives, Cytarabine therapeutic use, Etoposide therapeutic use, Glomerular Filtration Rate, Humans, Hydroxycholecalciferols blood, Hydroxyproline blood, Hypercalcemia drug therapy, Ifosfamide therapeutic use, L-Lactate Dehydrogenase blood, Lymphoma, B-Cell drug therapy, Lymphoma, B-Cell metabolism, Male, Osteocalcin blood, Parathyroid Hormone blood, Parathyroid Hormone-Related Protein, Prednisolone therapeutic use, Procarbazine therapeutic use, Hypercalcemia etiology, Lymphoma, B-Cell complications, Proteins physiology
- Abstract
Hypercalcemia occurred in a patient with non-Hodgkin's (B-cell type) lymphoma when generalized lymphadenopathy developed. Despite low normal plasma parathyroid hormone (PTH), nephrogenous cAMP (NcAMP) was not suppressed, and serum and urine PTH-related protein (PTH-rP) levels were elevated. The plasma level of 1,25(OH)2D was within normal range. The combined chemotherapies successfully reduced the tumor size, serum Ca, PTH-rP, and lactic dehydrogenase. Serum osteocalcin was suppressed while the patient was hypercalcemic, and increased after chemotherapy. In the extract of the tumor tissue obtained post mortem, bioactivity stimulating the production of cAMP in osteoblasts was demonstrated along with the immunoreactive PTH-rP. This is the first report of a B-cell lymphoma producing PTH-rP and its association with humoral hypercalcemia of malignancy.
- Published
- 1992
- Full Text
- View/download PDF
40. ["Essential laboratory tests" in primary care medicine--experiences in Comprehensive Medicine, National Defense Medical College].
- Author
-
Takemura Y, Hayashi K, Kugai N, and Sekiguchi S
- Subjects
- Hospitals, University, Humans, Japan, Medical History Taking, Neoplasms diagnosis, Physical Examination, Clinical Laboratory Techniques trends, Primary Health Care
- Abstract
The "essential laboratory tests" were applied to 1,026 new patients visiting the outpatient unit of Comprehensive Medicine, National Defense Medical College, to determine the usefulness of these tests in primary care medicine. The "essential laboratory tests" have contributed to the establishment of the initial diagnosis or confirmation of the "tentative initial diagnosis", and to the estimation of the nature or degree of seriousness of the disease. In addition, other diseases not related to the patient's chief complaint could be screened in 32% of the new patients examined with these tests. The "essential laboratory tests" were also found to be useful for the estimation of the presence of malignant tumors in 12 patients with various kinds of malignancies as well as the estimation or evaluation for such conditions as infection or inflammation, anemia, liver or renal dysfunction, and the ambulatory screening of metabolic diseases including hyperlipidemia, liver or urinary tract diseases. In conclusion, simultaneous performance of the "essential laboratory tests" with the history taking and the physical examination will provide important medical information in primary care medicine.
- Published
- 1992
41. [Laboratory tests in primary care medicine: "essential laboratory tests" (2). Usefulness of hematological, biochemical and serological tests in diagnosis of new outpatients].
- Author
-
Takemura Y, Hayashi K, Miyoshi K, Mori S, Kugai N, and Sekiguchi S
- Subjects
- Blood Chemical Analysis, Clinical Laboratory Techniques, Female, Humans, Male, Predictive Value of Tests, Ambulatory Care, Diagnostic Tests, Routine, Hematologic Tests, Primary Health Care, Serologic Tests
- Abstract
We evaluated diagnostic utility of the hematological, biochemical and serological tests comprised in the "essential laboratory tests" advocated by the Japan Society of Clinical Pathology in 1,026 new patients visiting the outpatient unit of Comprehensive Medicine, National Defense Medical College. Of 750 evaluable patients, 52 showed anemia associated with such conditions as ulcer or cancer of digestive tract, inflammatory disease, or renal failure. Leukocytosis (greater than 9,000/microliters) was found only in 25 of 112 CRP-positive (greater than 0.3 mg/dl) patients, suggesting bacterial infection. Forty-four patients showed hypoproteinemia and/or hypoalbuminemia indicating chronic conditions including liver and inflammatory disease. Elevation of serum creatinine level was found in 4 patients subsequently diagnosed with renal failure, whereas 32 patients demonstrated elevated BUN. After application of the "essential laboratory tests", 97 patients were diagnosed with hyperlipidemia (total cholesterol greater than 230 mg/dl and/or triglyceride greater than 250 mg/dl). Determination of serum enzyme activity was useful not only for the diagnosis of liver dysfunction or biliary tract disease but also for those of hematological malignancies or myogenic disorders; however, in patients with abnormal values of LDH, gamma-GT and ALP, clinical significance was not clarified in 53%, 38% and 59%, respectively. These results indicate that the "essential laboratory tests" are useful in the following aspects of primary care medicine: for (1) estimation of the degree or nature of infection or inflammatory status; (2) classification of anemia and its relation to underlying diseases; (3) evaluation of patient general condition and protein-producible function of liver; (4) evaluation of renal function; (5) ambulatory screening for metabolic diseases such as hyperlipidemia; and (6) diagnosis of liver and biliary tract diseases.
- Published
- 1992
42. Diurnal change in heart rate variability in healthy and diabetic subjects.
- Author
-
Noritake M, Takase B, Kudoh K, Kugai N, Kurita A, and Nagata N
- Subjects
- Adolescent, Adult, Aged, Analysis of Variance, Electrocardiography, Ambulatory, Female, Humans, Male, Middle Aged, Reference Values, Circadian Rhythm physiology, Diabetes Mellitus, Type 2 physiopathology, Heart Rate physiology
- Abstract
We assessed the hourly coefficient of variance of RR intervals (CVRR) in 29 subjects with non-insulin-dependent diabetes mellitus and 19 age-matched healthy subjects using an ambulatory 24-hour ECG monitoring system. We also evaluated CVRR during 100 beats in both groups in the supine posture at 07:00 and 10:00 in the morning. Hourly CVRR showed an overt diurnal variation in both groups especially in the daytime and at midnight, but was significantly lower (p less than 0.05) in diabetic patients. CVRR during resting 100 beats at 07:00 was significantly higher (p less than 0.05) than that at 10:00 in both groups. These findings indicate that HRV shows an obvious diurnal variation in both groups. As a steep and marked change occurs in the morning, careful consideration is necessary to assess the test performed for a short time span at random times throughout the day, particularly in the morning.
- Published
- 1992
- Full Text
- View/download PDF
43. A case of anorexia nervosa with acute renal failure induced by rhabdomyolysis; possible involvement of hypophosphatemia or phosphate depletion.
- Author
-
Wada S, Nagase T, Koike Y, Kugai N, and Nagata N
- Subjects
- Acute Kidney Injury blood, Adolescent, Anorexia Nervosa blood, Female, Humans, Phosphates deficiency, Rhabdomyolysis blood, Acute Kidney Injury etiology, Anorexia Nervosa complications, Phosphates blood, Rhabdomyolysis complications
- Abstract
A 16-year-old girl with anorexia nervosa first presented with malnutrition, liver dysfunction, and rhabdomyolysis. Administration of fluid and nutrition saved her from the initial critical state, but acute renal failure followed. Laboratory examination revealed intrinsic renal failure induced by rhabdomyolysis. Latent phosphate depletion and refeeding-induced hypophosphatemia was implicated as the cause of rhabdomyolysis; however coexisting hypotension, dehydration, and liver dysfunction may have contributed to the renal failure. The patient recovered from azotemia by hemodialysis. This is the first reported case of anorexia nervosa with acute renal failure resulting from rhabdomyolysis induced by hypophosphatemia or phosphate depletion.
- Published
- 1992
- Full Text
- View/download PDF
44. A case of asymptomatic cortisol producing adrenal adenoma.
- Author
-
Noritake M, Morimoto K, Kosano H, Nemoto Y, Kugai N, Takao M, Murai M, Tamai S, Tanaka K, and Nagata N
- Subjects
- Adenoma pathology, Adenoma surgery, Adrenal Gland Neoplasms pathology, Adrenal Gland Neoplasms surgery, Cushing Syndrome etiology, Dexamethasone, Humans, Hypothalamo-Hypophyseal System physiopathology, Male, Metyrapone, Middle Aged, Pituitary-Adrenal System physiopathology, Adenoma metabolism, Adrenal Gland Neoplasms metabolism, Hydrocortisone metabolism
- Abstract
We describe a man without the clinical findings of Cushing's syndrome, but who harbored an incidentally found cortisol-producing adrenal adenoma. On adrenal 131I-adsterol imaging, there was good uptake to the nodule, but no visualization of the contralateral adrenal. No abnormalities were found in the basal plasma cortisol, ACTH, urinary free cortisol and 17OHCS. However, dynamic hormone assessment revealed the existence of abnormal cortisol secretion: no suppression to dexamethasone, incomplete response to human corticotropin-releasing hormone, and lack of diurnal variation in plasma cortisol. Left adrenalectomy was performed with the diagnosis of cortisol-producing adrenal tumor. The pathological finding was an adrenal adenoma, and the perifusion of the excised tissues revealed a negligible response of the tumor tissue to ACTH though the residual normal cortex responded. Postoperative course was uneventful without replacement therapy with cortisol. It is suggested that the tumor autonomously produced a small amount of cortisol not only insufficient to provide clinical Cushing's syndrome, but also to provide typical suppression of hypothalamo-pituitary corticotroph-adrenal system.
- Published
- 1992
- Full Text
- View/download PDF
45. [Usefulness of "essential laboratory tests" for the establishment of the initial diagnosis in new outpatients].
- Author
-
Takemura Y, Hayashi K, Kugai N, and Sekiguchi S
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Ambulatory Care, Comprehensive Health Care, Female, Humans, Male, Medical History Taking, Middle Aged, Physical Examination, Predictive Value of Tests, Diagnostic Tests, Routine
- Abstract
"Essential laboratory tests" advocated by Japan Society of Clinical Pathology were simultaneously performed with the history taking of the present illness and the physical examination in 1,026 new patients visited the outpatient unit of Comprehensive Medicine, National Defense Medical College. We have analyzed the usefulness of the "essential laboratory tests" for the establishment of the initial diagnosis in evaluable 750 patients by comparing the diagnosis made only by the history taking and the physical examination (tentative initial diagnosis) with that included the results of these laboratory tests. The "essential laboratory tests" had contributed to remarkably increased incidences of metabolic and endocrine diseases, liver or biliary tract diseases, renal and urinary tract diseases and anemia after the application of these tests. The initial diagnoses of 61 patients were successfully established by the addition of the "essential laboratory tests" among 157 cases of which tentative initial diagnoses remained undetermined. These tests confirmed the tentative diagnoses in 78 patients, while 78 tentative diagnoses were negated and corrected after evaluation of the results of these tests. Furthermore, the diagnostic tests such as CRP and leukocyte count were useful for the estimation of the nature or degree of seriousness of the disease in 57 patients. In addition, other diseases not related to the patient's chief complaint could be detected in 238 patients (303 total number of diseases) by these tests. These results indicate the usefulness of the "essential laboratory tests" not only for the establishment of more accurate initial diagnosis but also for the screening of the "hidden" diseases such as hyperlipidemia and liver dysfunction.
- Published
- 1992
46. Simultaneous occurrence of SIADH, secondary hypogonadism and alopecia universalis in a woman with IDDM.
- Author
-
Yasutomo Y, Yoshida A, Noritake M, Nemoto Y, Kugai N, and Nagata N
- Subjects
- Adrenocorticotropic Hormone blood, Adult, Alopecia blood, Clomiphene pharmacology, Diabetes Mellitus, Type 1 blood, Female, Follicle Stimulating Hormone blood, Growth Hormone blood, Humans, Hydrocortisone blood, Hypogonadism blood, Inappropriate ADH Syndrome blood, Insulin pharmacology, Luteinizing Hormone blood, Pituitary Gland drug effects, Pituitary Gland metabolism, Prolactin blood, Thyroid Hormones blood, Thyrotropin blood, Vasopressins blood, Alopecia etiology, Diabetes Mellitus, Type 1 complications, Hypogonadism etiology, Inappropriate ADH Syndrome etiology
- Abstract
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH), hypothalamic hypogonadism and alopecia universalis occurred in a 31-year-old female with insulin-dependent diabetes mellitus (IDDM). Despite various clinical investigations and careful observation for 20 months, the cause and pathogenesis of SIADH and hypothalamic hypogonadism were not elucidated. The complex of these disorders had not been described. The presence of IDDM and alopecia universalis, in which an autoimmune process has been assumed to be involved, is interesting in considering the pathogenesis of the SIADH and hypothalamic hypogonadism.
- Published
- 1991
- Full Text
- View/download PDF
47. The effect of PGF2 alpha on parathyroid hormone-stimulated cyclic AMP production in mouse osteoblastic cell, MC3T3E1.
- Author
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Wada S, Yasutomo Y, Kosano H, Kugai N, and Nagata N
- Subjects
- Animals, Calcimycin pharmacology, Cell Line, Cell Membrane enzymology, Kinetics, Mice, Osteoblasts cytology, Osteoblasts drug effects, Protein Kinase C antagonists & inhibitors, Protein Kinase C metabolism, Tetradecanoylphorbol Acetate pharmacology, Cyclic AMP biosynthesis, Dinoprost pharmacology, Osteoblasts metabolism, Parathyroid Hormone pharmacology
- Abstract
The effect of prostaglandin F2 alpha (PGF2 alpha) was investigated in MC3T3E1 cells on the succeeding cAMP response to parathyroid hormone (PTH). PGF2 alpha increased the membrane-associated protein kinase C (PKC) activity, indicating the activation of this enzyme. The effect of PTH to increase cAMP production was enhanced by pretreatment with PGF2 alpha. Phorbol 12-myristate 13-acetate also enhanced cAMP production stimulated by PTH, and PKC inhibitor H7 attenuated the enhancement of PGF2 alpha. A23187 did not reproduce the PGF2 alpha effect, and this effect was not antagonized by the calmodulin antagonist W7. PGF2 alpha did not change the ED50 nor the maximally responsive dose of PTH in stimulating cAMP production. The effect of PGF2 alpha was not affected by pertussis toxin, and PGF2 alpha also enhanced cholera toxin- or forskolin-stimulated cAMP production. In accordance with the response of cAMP to PTH, the resorption of mouse limb bones stimulated submaximally by PTH was enhanced by the concomitant presence of PGF2 alpha. These results indicate that PGF2 alpha modulates cAMP response through the activation of PKC, the target of which might be the catalytic unit of adenylate cyclase. Such interaction between signal transduction systems may have significance in modulating the effect of PTH on bone, i.e., bone resorption.
- Published
- 1991
- Full Text
- View/download PDF
48. Purification and partial sequencing of inhibitory factor on renal membrane adenylate cyclase in pancreatic cancer extract: identity with histones H1b or H1d.
- Author
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Yasutomo Y, Suga T, Wada S, Kosano H, Takishima K, Mamiya G, Kugai N, and Nagata N
- Subjects
- Amino Acid Sequence, Animals, Cell Line, Cell Membrane enzymology, Dogs, Histones genetics, Histones isolation & purification, Humans, Hypercalcemia etiology, Hypercalcemia physiopathology, Molecular Sequence Data, Molecular Weight, Pancreatic Neoplasms chemistry, Sequence Homology, Nucleic Acid, Adenylyl Cyclases isolation & purification, Histones pharmacology, Kidney Cortex enzymology, Pancreatic Neoplasms physiopathology
- Abstract
Inhibitory activity on renal membrane adenylate cyclase (AC) has previously been found in the extract of a pancreatic cancer associated with humoral hypercalcemia of malignancy (HHM). AC inhibitor was purified employing inhibition of AC activity of renal membrane stimulated by forskolin as its index. N-terminal 9 residues and a digested fragment of purified protein (14 residues) were completely consistent with that of histones H1b and H1d. Not only histone H1 but also histones H2A, H2B and H3 from calf thymus inhibited AC activity. These results indicate that the AC inhibitor in the pancreatic cancer extract is histone H1b or H1d and histones H2A, H2B and H3 also have an AC inhibitory activity.
- Published
- 1991
- Full Text
- View/download PDF
49. Hypopituitarism associated with Cogan's syndrome; high-dose glucocorticoid therapy reverses pituitary swelling.
- Author
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Kanatani M, Nakamura R, Kurokawa K, Taoda M, Nemoto Y, Kamakura K, Kugai N, Nagata N, Takatani O, and Tsuchiya K
- Subjects
- Aged, Deamino Arginine Vasopressin therapeutic use, Diabetes Insipidus drug therapy, Diabetes Insipidus etiology, Female, Humans, Hyperprolactinemia etiology, Hypopituitarism drug therapy, Hypopituitarism pathology, Pituitary Gland pathology, Syndrome, Autoimmune Diseases complications, Facial Paralysis etiology, Hypopituitarism etiology, Meningitis, Aseptic etiology, Prednisolone therapeutic use, Vasculitis complications, Vestibular Diseases etiology
- Abstract
A 70-year-old woman with Cogan's syndrome first presented with central diabetes insipidus and then developed secondary hypothyroidism. Magnetic resonance imaging revealed a diffuse pituitary swelling without evidence of tumor. High-dose glucocorticoid therapy administered to treat Cogan's syndrome was very effective in suppressing the inflammatory process, and resulted in the reversal of the pituitary swelling and partial recovery of thyroid stimulating hormone secretion. This is the first case of hypopituitarism associated with Cogan's syndrome, a form of autoimmune vasculitis. The glucocorticoid-responsive pituitary lesion is best explained by autoimmune hypophysitis which shows pituitary swelling and is known to often associate with other autoimmune phenomena.
- Published
- 1991
- Full Text
- View/download PDF
50. [Laboratory tests in primary care medicine: "essential laboratory tests" (1). Urinalysis].
- Author
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Sekiguchi S, Kugai N, Miyoshi K, Hayashi K, Mori S, Takemura Y, and Tamai S
- Subjects
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Female, Glycosuria, Humans, Leukocyte Count, Male, Middle Aged, Occult Blood, Proteinuria, Sex Factors, Urine cytology, Primary Health Care, Urine chemistry
- Abstract
Japan Society of Clinical Pathology has formed a committee dealing with "lab. tests in primary care medicine". As the first step, they made "Essential Lab. Tests" which were composed of simple qualitative bed-side tests such as urinalysis, Complete blood count (CBC: Hb, Ht, WBC, RBC), CRP, or ESR (Erythrocyte sedimental rate), A/G ratio and biochemical tests if necessary (Table 1). We have performed "Essential Lab. Tests" on 1,026 outpatients who visited General Medicine Clinic for the first time. They consisted of 456 male (age 13-81), and 526 female (age 10-85). This report is the result of urinalysis from "Essential Lab. Tests" of 1,026 patients. 1) The result showed that overall positivity of the urinalysis was 21.3% (when more than one item of the qualitative tests was positive). 2) There was distinctive difference in the positivity of the urinalysis between the sex; i.e. protein and glucose were about twice frequently positive in male, where as occult blood and WBC (Esterase reaction) were 2-3 times more positive in female. 3) Urine protein shows positive in the individual 10-20 yrs old and more than 50 yrs old in both sexes. 4) Glucose was positive in over 40 yrs in male, and occult blood, 40-50 yrs or older in male. 5) WBC shows positive in all age groups in female and 50 yrs or older in male. 6) Positive WBC patients did not necessarily reflect urinary infection in female but nitrites roughly corresponded with urinary WBC in male of 50 yrs or older, meaning probable urinary infection associated with prostatic hypertrophy. 7) Abnormality of urinary sediment corresponded to the positive occult blood and WBC Erastase. 8) Urinalysis is an useful method of screening in primary care medicine.
- Published
- 1990
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