34 results on '"Naomi Funaki"'
Search Results
2. Continuous hepatocyte growth factor supply prevents lipopolysaccharide-induced liver injury in rats
- Author
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Toshikazu Nakamura, Shin Ichi Seto, Toshimi Kaido, Masayuki Imamura, Takayuki Kasamatsu, Junji Tanaka, Shoji Yamaoka, and Naomi Funaki
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Lipopolysaccharides ,Male ,CCl4 ,medicine.medical_specialty ,Lipopolysaccharide ,Cell Transplantation ,Biophysics ,Spleen ,CCL4 ,Liver injury ,Biology ,Biochemistry ,Transaminase ,chemistry.chemical_compound ,Endotoxin ,Structural Biology ,Internal medicine ,Genetics ,medicine ,Animals ,Humans ,Aspartate Aminotransferases ,Carbon Tetrachloride ,Molecular Biology ,Hepatocyte growth factor ,Protection ,Hepatotoxin ,Alanine Transaminase ,Cell Biology ,Fibroblasts ,medicine.disease ,Endotoxemia ,Rats, Inbred F344 ,Recombinant Proteins ,Rats ,Endotoxins ,medicine.anatomical_structure ,Endocrinology ,Liver ,chemistry ,Immunology ,Carbon tetrachloride ,medicine.drug - Abstract
We present a rat model in which continuous supply of hepatocyte growth factor (HGF) prevents liver injury induced by carbon tetrachloride (CCl4) and E. coli 011:B4 lipopolysaccharide (LPS). Rat fibroblasts genetically modified to secrete rat HGF were implanted in syngenic rat spleen 7 days before administration of the hepatotoxins. Rats with HGF-secreting fibroblasts in the spleen showed a dramatic resistance to CCl4- and LPS-induced liver injury. In the LPS-induced liver injury model, blood chemical analysis revealed that the increase in serum glutamic oxalacetic transaminase level and the decrease in blood sugar level were remarkably suppressed in rats with HGF-secreting cells in the spleen. Most importantly, their survival rate was greatly improved compared to other control groups of rats. Thus our results indicate a new role of HGF in liver protection during endotoxemia and convey important clinical implications for developing new therapeutic modalities in the treatment of liver failure caused by endotoxemia.
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- 1997
3. Detection of colorectal carcinoma cells in circulating peripheral blood by reverse transcription-polymerase chain reaction targeting cytokeratin-20 mRNA
- Author
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Junji Tanaka, Naomi Funaki, Takashi Okino, Hisashi Onodera, Atsushi Itami, Kazunobu Monden, Gakuji Ohshio, Takayuki Kasamatsu, and Masayuki Imamura
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Adult ,Male ,DNA, Complementary ,Colorectal cancer ,Keratin-20 ,Biology ,Polymerase Chain Reaction ,Sensitivity and Specificity ,General Biochemistry, Genetics and Molecular Biology ,Cytokeratin ,Intermediate Filament Proteins ,Biomarkers, Tumor ,Tumor Cells, Cultured ,medicine ,Humans ,RNA, Messenger ,RNA, Neoplasm ,General Pharmacology, Toxicology and Pharmaceutics ,Aged ,DNA Primers ,Messenger RNA ,Base Sequence ,Keratin 20 ,DNA, Neoplasm ,General Medicine ,Middle Aged ,Neoplastic Cells, Circulating ,medicine.disease ,Molecular biology ,Reverse transcriptase ,Reverse transcription polymerase chain reaction ,Real-time polymerase chain reaction ,Female ,Colorectal Neoplasms ,Nested polymerase chain reaction - Abstract
For the detection of circulating colorectal carcinoma cells, we investigated the presence of cytokeratin 20 (CK 20) mRNA in the peripheral blood of colorectal carcinoma patients. Application of our published technique resulted in analysis by reverse transcription followed by three-step nested polymerase chain reaction. This analysis could detect a single Colo 205 colon cancer cell mixed with 1 ml of blood. Our system also successfully detected the presence of CK 20 mRNA in actual patients' peripheral blood samples. Our highly sensitive and specific system for the detection of CK-20 mRNA from patients' peripheral blood thus seems to be useful for screening for circulating colorectal carcinoma cells.
- Published
- 1997
4. Identification of carcinoembryonic antigen mRNA in circulating peripheral blood of pancreatic carcinoma and gastric carcinoma patients
- Author
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Naomi Funaki, Junji Tanaka, Gakuji Ohshio, Masayuki Imamura, Ryo Hosotani, Takayuki Kasamatsu, and Takashi Okino
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Male ,Pathology ,medicine.medical_specialty ,Polymerase Chain Reaction ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,Carcinoembryonic antigen ,Stomach Neoplasms ,medicine ,Carcinoma ,Humans ,RNA, Messenger ,General Pharmacology, Toxicology and Pharmaceutics ,Aged ,Aged, 80 and over ,biology ,business.industry ,Gastric lymphoma ,General Medicine ,Middle Aged ,medicine.disease ,digestive system diseases ,Carcinoembryonic Antigen ,Pancreatic Neoplasms ,Real-time polymerase chain reaction ,biology.protein ,Pancreatitis ,Adenocarcinoma ,Female ,Gastritis ,medicine.symptom ,business - Abstract
To detect adenocarcinoma cells in the circulating peripheral blood, we analyzed the presence of carcinoembryonic antigen (CEA) mRNA in the peripheral blood obtained from patients with pancreatic carcinoma (PC) or with gastric carcinoma (GC) and also, as controls, from pancreatitis or gastritis patients without carcinomas, a gastric lymphoma patient and four healthy volunteers. Because of the small number of carcinoma cells expected in the peripheral blood, the analysis was performed by the reverse transcription followed by an original two-step polymerase chain reaction. By this sensitive method, 3 of 9 PC patients and 2 of 9 GC patients were positive for CEA mRNA. Except for 1 highly advanced PC patient, 3 of 4 CEA mRNA-positive patients developed recurrence after curative resection or liver metastasis after palliative operation within 9 months after the analysis. None of the control patients was positive for CEA mRNA in the peripheral blood. The results suggest that our sensitive RT-PCR method for detecting CEA mRNA in the peripheral blood is practically useful to find the hematogenous spreading of adenocarcinoma cells.
- Published
- 1996
5. Chemical mediators released by primary-cultured human hepatic macrophages in patients with and without cirrhosis: A study in tumor-bearing patients
- Author
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Masahiro Mise, Kazunobu Monden, Naomi Funaki, Masayuki Imamura, Junji Tanaka, Masaharu Furutani, Hisako Higashitsuji, and Shigeki Arii
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Pathology ,Cirrhosis ,Dinoprostone ,chemistry.chemical_compound ,Adjuvants, Immunologic ,Superoxides ,Internal medicine ,medicine ,Humans ,Macrophage ,Secretion ,Prostaglandin E2 ,Cells, Cultured ,Hepatology ,business.industry ,Macrophages ,Liver Neoplasms ,Zymosan ,Interleukin ,medicine.disease ,Liver ,chemistry ,Cell culture ,business ,Interleukin-1 ,medicine.drug - Abstract
To elucidate the possible role of chemical mediators in modulating the host-defense activity of patients with cirrhosis, primary-cultured human hepatic macrophages (HHMphi) were obtained from cirrhotic and noncirrhotic patients who received liver resections because of the presence of malignant liver tumors. The cirrhotic and noncirrhotic groups consisted of patients with similar malignancies: noncirrhotic patients had normal liver function and normal liver histology for nontumorous portions. The cultured HHMphi were analyzed for their ability to release chemical mediators with specific activities in the host defense system. Dose-dependent increases in superoxide release, interleukin-1 (IL-1) release, and, within a relatively narrow range, prostaglandin-E2 (PGE2) release were observed in opsonized zymosan (oz)-stimulated HHMphi derived from both cirrhotic and noncirrhotic patients. The release of O2- and PGE2 from HHMphi derived from cirrhotic patients was significantly less than HHMphi derived from noncirrhotic patients, whereas the release of IL-1 was significantly greater. Although, because of the limited sample availability, only tumor-bearing patients were studied, the mediator-releasing ability of HHMphi derived from cirrhotic patients was significantly different from the ability of HHMphi derived from noncirrhotic patients with similar malignancies. This phenomenon may be related to altered host defenses in patients with cirrhosis. (Hepatology 1996 Jun;23(6):1353-8)
- Published
- 1996
6. Highly-sensitive identification of α-fetoprotein mRNA in circulating peripheral blood of hepatocellular carcinoma patients
- Author
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Takayuki Kasamatsu, Masayuki Imamura, Naomi Funaki, Junji Tanaka, Shin-ichi Seto, and Toshimi Kaido
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,DNA, Complementary ,Transcription, Genetic ,Polymerase Chain Reaction ,General Biochemistry, Genetics and Molecular Biology ,law.invention ,Text mining ,law ,Carcinoma ,medicine ,Humans ,RNA, Messenger ,General Pharmacology, Toxicology and Pharmaceutics ,neoplasms ,Polymerase chain reaction ,Aged ,Messenger RNA ,business.industry ,General Medicine ,Middle Aged ,Neoplastic Cells, Circulating ,medicine.disease ,digestive system diseases ,Reverse transcriptase ,Peripheral blood ,Hepatocellular carcinoma ,Female ,alpha-Fetoproteins ,business ,Alpha-fetoprotein ,Follow-Up Studies - Abstract
In order to capture hepatocellular carcinoma (HCC) cells in circulating peripheral blood, we made analysis to see if alpha-fetoprotein (AFP) mRNA exists in the peripheral blood obtained from patients with HCC and also, as a control, from hepatitis-viral-marker-positive patients without HCC and a healthy volunteer. As the number of HCC cells in peripheral blood and the quantity of AFP mRNA are expected to be very small, the analysis was performed by the reverse transcription followed by an original three-step polymerase chain reaction. By this highly-sensitive method, 5 of 7 HCC patients were positive for AFP mRNA. These 5 positive patients consisted of three with clinically apparent recurrence, one preoperative patient with tumor thrombus in the portal vein and one recurrence-free patient who developed clinically detectable recurrence three months after this analysis. Neither 4 patients with positive viral markers nor a healthy volunteer was positive. The results suggest that detection of AFP mRNA from HCC patients' peripheral blood by our highly-sensitive RT-PCR may be a practical and powerful tool to diagnose the preoperative spreading of HCC and to monitor its recurrence.
- Published
- 1995
7. Identification of the thromboxane A2 receptor in hepatic sinusoidal endothelial cells and its role in Endotoxin-induced liver injury in rats
- Author
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Satoshi Ishiguro, Fumitaka Ushikubi, Tousei Ohmura, Shuh Narumiya, Ken‐Ichi ‐I Nakamura, Shigeki Arii, Naomi Funaki, Masayuki Imamura, Shin‐Ichi ‐I Fujita, Katsuhiko Enomoto, Michio Mori, Tadahiro Kitao, Masahiro Mise, Hiroaki Higashitsuji, Kazunobu Monden, Masaharu Furutani, Toshio Nakamura, and Yukito Adachi
- Subjects
Liver injury ,medicine.medical_specialty ,Hepatology ,biology ,Thromboxane ,Chemistry ,Ligand binding assay ,Kupffer cell ,medicine.disease ,Thromboxane receptor ,Thromboxane A2 ,chemistry.chemical_compound ,medicine.anatomical_structure ,Endocrinology ,Internal medicine ,medicine ,biology.protein ,Cyclooxygenase ,Receptor - Abstract
The presence of the thromboxane A2 receptor in sinusoidal endothelial cells was investigated and its pathogenic role in endotoxin-induced liver injury examined. The receptor was measured with a binding assay using a specific thromboxane A2 receptor antagonist, [3H]S-145. Scatchard analysis of the binding indicated the presence of a single class of high-affinity binding sites with a dissociation constant of 5.00 ± 0.96 nmol/L, a maximal binding of 22.85 ± 2.71 fmol/106 cells and 13.80 ± 1.60 × 103 binding sites per cell. The addition of a cyclooxygenase inhibitor, indomethacin, during the cell preparation increased the maximal binding value and the number of binding sites of 37.34 ± 3.01 and 22.50 ± 1.80 × 103 sites/cell, respectively. The binding was displaced by various thromboxane A2 analogs such as ONO-3708 and STA2 but was not effectively competed for by other prostaglandins. Endotoxin injection reduced dissociation constant, maximal binding and the number of binding sites in sinusoidal endothelial cells to 3.49 ± 0.87 nmol/L, 6.03 ± 0.64 fmol/106 cells and 3.65 ± 0.39 × 103 sites/cell, respectively. A cyclooxygenase inhibitor and a Kupffer cell inhibitor added before endotoxin treatment significantly prevented the reduction in the number of thromboxane A2 receptors. It is possible that these effects were due to a reduction in the agonist-induced internalization of the thromboxane A2 receptor brought about by the prevention of thromboxane A2 production. Preadministration of both a cyclooxygenase inhibitor and a thromboxane A2 receptor antagonist attenuated the degree of endotoxininduced liver injury. These findings indicated that the thromboxane A2—thromboxane A2 receptor system in the hepatic sinusoids plays a significant role in the pathogenesis of endotoxin-dependent liver damage. (Hepatology 1994;20:1281–1286).
- Published
- 1994
8. Augmented local immunity in the liver by a streptococcal preparation, OK432, related to antitumor activity of hepatic macrophages
- Author
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Toshio Nakamura, Jun Fujita, Naomi Funaki, Satoshi Ishiguro, Hiroki Nakayama, Tadahiro Kitao, Yukito Adachi, Shinichi Fujita, Kazunobu Monden, Shigeki Arii, Masaharu Furutani, Masayuki Imamura, Masahiro Mise, and Hiroaki Higashitsuji
- Subjects
Cytotoxicity, Immunologic ,Male ,Interleukin 2 ,medicine.drug_class ,medicine.medical_treatment ,In Vitro Techniques ,Pharmacology ,Biology ,Immunostimulant ,Picibanil ,Immune system ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Cytotoxic T cell ,RNA, Messenger ,IL-2 receptor ,Tumor Necrosis Factor-alpha ,Liver Neoplasms ,Interleukin ,Receptors, Interleukin-2 ,Macrophage Activation ,Rats ,Cytokine ,Liver ,Immunology ,Tumor necrosis factor alpha ,Interleukin-1 ,medicine.drug - Abstract
The aim of this study was to investigate the augmentative effect of a streptococcal preparation, OK432, on the immunological competence of hepatic macrophages. We found that OK432 was distributed predominantly to hepatic macrophages after intravenous injection, and Northern blot analysis revealed that OK432 induced the gene expression of IL-1 alpha, beta, and TNF alpha in the liver. The induction of mRNAs was evident 1 h after the intravenous injection of OK432 and their accumulation reached a maximal level at 3 h. TNF production of hepatic macrophages was also increased by the intravenous injection of OK432. Furthermore, OK432 significantly increased the proportion of IL-2 receptor-positive hepatic macrophages. As for antitumor activity in the liver being augmented by OK432, the cytotoxic and cytostatic activity of hepatic macrophages from OK432-treated rats against tumor cells was significantly increased and OK432 markedly reduced the number of tumor nodules in the liver after the inoculation of tumor cells via the portal vein. These findings, which indicate that OK432 has various immuno-stimulating actions on hepatic macrophages, leading to the augmentation of antitumor activity in the liver, suggest that OK432 may be of some benefit in helping to prevent hepatic metastasis, at least in part, via its activation of hepatic macrophages.
- Published
- 1994
9. The Role of Kupffer Cells in the Surveillance of Tumor Growth in the Liver
- Author
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Naomi Funaki, Wenhai Zhang, Tetsu Sasaoki, Shinichi Fujita, Satoshi Ishiguro, Hiroaki Higashitsuji, Masahiro Mise, Yukito Adachi, Shigeki Arii, Makoto Naito, Masaharu Furutani, Tadahiro Kitao, and Takayoshi Tobe
- Subjects
Cytotoxicity, Immunologic ,Male ,Pathology ,medicine.medical_specialty ,Kupffer Cells ,medicine.drug_class ,Mast-Cell Sarcoma ,Biology ,Monoclonal antibody ,Mice ,Liver Neoplasms, Experimental ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Macrophage ,Rats, Wistar ,Cytotoxicity ,Leukemia ,Macrophages ,Kupffer cell ,Antibodies, Monoclonal ,medicine.disease ,Molecular biology ,Chromium Radioisotopes ,Rats ,medicine.anatomical_structure ,Splenectomy ,biology.protein ,Mast cell sarcoma ,Autoradiography ,Surgery ,Antibody ,Cell Division ,K562 cells - Abstract
The present study was designed to investigate the role of Kupffer cells (Kc) in the surveillance of liver tumors. We examined the antitumor activity of Kc by 51Cr releasing assay and inhibition of [3H]thymidine ([3H]TdR) incorporation into tumor cells. We also studied the change in the growth of liver tumors following the activation and the blockade of Kc. The cytotoxicity of Kc against K562 increased as the effector:target (E:T) ratio rose and reached its maximum level of about 18% at an E:T ratio of 20:1. [3H]TdR incorporation into target cells (P815 and AH130) was also inhibited by Kc. Such antitumor activity of Kc was augmented by OK432 (K562, from 13.8 +/- 5.6 to 21.9 +/- 2.5%; AH130, from 19.2 +/- 14.5 to 37.1 +/- 12.6%). In the experiment of the inoculation of AH130 via the portal vein, OK432 decreased the number of hepatic foci, whereas macrophage inhibitors carrageenan and gadolinium increased the number of tumor nodules. In addition, gadolinium injection reduced the number of Kupffer cells reactive with monoclonal antibodies directed against macrophages ED2 and Ki-M2R. Tumor growth in the liver was maximum in rats with both gadolinium treatment and splenectomy. In conclusion, Kc have antitumor activity, and augmentation of Kc may be a possible strategy to prevent hematogenous hepatic metastasis.
- Published
- 1993
10. Prostaglandin E2 production by hepatic macrophages and peripheral monocytes in liver cirrhosis patients
- Author
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Masayuki Imamura, Naomi Funaki, Hiroaki Higashituji, Shigeki Arii, Junji Tanaka, and Yukito Adachi
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,medicine.medical_treatment ,Monocytes ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Choline ,General Pharmacology, Toxicology and Pharmaceutics ,Prostaglandin E2 ,Cells, Cultured ,Cholinesterase ,biology ,Liver Diseases ,Macrophages ,Prostaglandins E ,Monocyte ,General Medicine ,medicine.disease ,Pathophysiology ,Endocrinology ,medicine.anatomical_structure ,Liver ,chemistry ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Liver function ,Prostaglandin E ,medicine.drug - Abstract
We analyzed PGE2 production in primary-cultured human hepatic macrophages (HHM phi) and peripheral monocytes (MO) from patients with and without liver cirrhosis, and correlated PGE2 production with the patients' liver function. Serum choline esterase (ChE) levels were used as an indicator of liver function. PGE2 production in both HHM phi and MO from cirrhotic patients was significantly lower than in HHM phi and MO from non-cirrhotic patients. PGE2 production in cirrhotic HHM phi was inversely correlated with ChE levels, whereas PGE2 production in cirrhotic MO showed no obvious correlation. In conclusion, both HHM phi and MO might contribute to the pathophysiology of liver cirrhosis via attenuated PGE2 production. Furthermore, HHM phi activity appears to be more strongly affected by the chronic pathological changes observed in the cirrhotic liver.
- Published
- 1993
11. Superoxide release by primary-cultured human hepatic macrophages and peripheral monocytes from patients with normal and cirrhotic livers
- Author
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Naomi Funaki, Junji Tanaka, Shigeki Arii, Yukito Adachi, Hiroaki Higashitsuji, and Takayoshi Tobe
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Pathology ,Cirrhosis ,Clinical Biochemistry ,Biology ,Monocytes ,chemistry.chemical_compound ,Superoxides ,Internal medicine ,medicine ,Humans ,Macrophage ,Cells, Cultured ,Aged ,Superoxide ,Macrophages ,Monocyte ,Superoxide release ,Alanine Transaminase ,General Medicine ,Middle Aged ,medicine.disease ,Peripheral ,Endocrinology ,medicine.anatomical_structure ,Liver ,chemistry ,Cell culture ,Tetradecanoylphorbol Acetate ,Liberation - Abstract
We analysed superoxide anion (O2-) release from primary-cultured human hepatic macrophages (HHM phi) and peripheral blood monocytes (MO) derived from patients with normal and cirrhotic livers. Primary cultured human hepatic macrophages and MO from cirrhotic patients released less O2- than cells from normal patients. Superoxide anion release by HHM phi showed a significant, positive correlation with the serum glutamate pyruvate transaminase (GPT) level, whereas O2- release by MO showed only a weak correlation with the GPT level. In conclusion, a significant reduction in O2- release was observed in HHM phi and MO cultured from cirrhotic patients. Primary-cultured human hepatic macrophages are probably more susceptible to environmental changes within the cirrhotic liver than MO, since they are found locally within the liver and correlate with serum GPT levels.
- Published
- 1993
12. Enhancement of rat hepatic macrophages by treatment with interleukin-2 and streptococcal preparation OK432, with reference to antitumor activity, soluble factor production and Ia expression
- Author
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Tetsu Sasaoki, Naomi Funaki, Shigeyuki Itai, Kazunobu Monden, Hiroaki Higashituji, Shigeki Arii, Takayoshi Tobe, and Yukito Adachi
- Subjects
Cytotoxicity, Immunologic ,Male ,Interleukin 2 ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Pharmacology ,Biology ,Picibanil ,Superoxides ,In vivo ,Internal medicine ,Cell Adhesion ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Immunologic Factors ,Immunology and Allergy ,Macrophage ,Carbon Radioisotopes ,Cytotoxicity ,Tumor Necrosis Factor-alpha ,Macrophages ,Histocompatibility Antigens Class II ,Rats, Inbred Strains ,Neoplasms, Experimental ,Cytostasis ,In vitro ,Rats ,Cytokine ,Endocrinology ,Liver ,Oncology ,Autoradiography ,Interleukin-2 ,Tumor necrosis factor alpha ,medicine.drug - Abstract
The effect of biological response modifiers, such as interleukin-2 (IL-2) and streptococcal preparation OK432, on the functions of hepatic macrophages was investigated. The macrophages, even with no exogenous stimulation, produced superoxide anion (O2-) and tumor necrosis factor (TNF), displayed cytotoxicity against K562 cells and cytostasis against P815 cells and expressed immune-region-associated antigen (Ia). IL-2 administered in vitro or in vivo enhanced O2- production by hepatic macrophages and the intravenous injection of OK432 also enhanced O2- production. Furthermore, IL-2 added to the culture medium of hepatic macrophages isolated from OK432-injected rats augmented O2- production even more. The TNF production and Ia expression of the macrophages were also increased by the intravenous injection of OK432. As with O2- production, the cytotoxicity of the cells was enhanced by OK432 injection or by IL-2 added to the culture medium and the combination of OK432 and IL-2 augmented their cytotoxicity even more. Thus, the present study suggested that IL-2 and OK432 induce the augmentation of the antitumor activity of hepatic macrophages, partly as a result of the increase in production of O2- and TNF and Ia expression.
- Published
- 1992
13. Effect of PGE2 on interleukin-1 and superoxide release from primary-cultured human hepatic macrophages
- Author
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Hiroaki Higashituji, Satoshi Ishiguro, Yukito Adachi, Shigeki Arii, Junji Tanaka, Takayoshi Tobe, Masaharu Furutani, Shinichi Fujita, Naomi Funaki, Tadahiro Kitao, and Masahiro Mise
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Indomethacin ,Endogeny ,Biology ,Dinoprostone ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Superoxides ,In vivo ,Internal medicine ,medicine ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Prostaglandin E2 ,Cells, Cultured ,Dose-Response Relationship, Drug ,Superoxide ,Macrophages ,Kupffer cell ,Interleukin ,General Medicine ,Mononuclear phagocyte system ,Cytokine ,medicine.anatomical_structure ,Endocrinology ,Liver ,chemistry ,lipids (amino acids, peptides, and proteins) ,Interleukin-1 ,medicine.drug - Abstract
In order to learn more about how human hepatic macrophages function, we analyzed the effect of exogeneous PGE2 on the amounts of interleukin-1 (IL-1) and superoxide (O2−) released from primary-cultured human hepatic macrophages (HHMΦ). When endogenous PGE2 production was blocked by indomethacin, exogenous PGE2 reduced IL-1 release from HHMΦ in a dose-dependent manner, whereas it tended to increase O2- release from HHM Φ. These results may suggest the probable contribution of PGE2 in regulating HHMΦ mediator release in vivo.
- Published
- 1992
14. Tumoricidal activity of Kupffer cells augmented by anticancer drugs
- Author
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Takayoshi Tobe, Hiroaki Higashitsuji, Masahiro Mise, Yukito Adachi, Naomi Funaki, Wenhai Zhang, Shinichi Fujita, Masaharu Furutani, and Shigeki Arii
- Subjects
Male ,Kupffer Cells ,medicine.drug_class ,Mitomycin ,Antibiotics ,Fluorescent Antibody Technique ,Mast-Cell Sarcoma ,Biology ,Pharmacology ,digestive system ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Liver Neoplasms, Experimental ,Antigen ,Superoxides ,Tumor Cells, Cultured ,medicine ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,Receptor ,Superoxide ,Kupffer cell ,Rats, Inbred Strains ,Receptors, Interleukin-2 ,Mastocytoma ,General Medicine ,medicine.disease ,Rats ,medicine.anatomical_structure ,chemistry ,Mechanism of action ,Doxorubicin ,Antigens, Surface ,Growth inhibition ,medicine.symptom - Abstract
The effect of Mitomycin-C (MMC) and Adriamycin (ADM) on the antitumor-associatted function of Kupffer cells was examined. MMC and ADM enhanced the production of superoxide by Kupffer cells in cultures at low concentrations likely to occur in clinical use. The expression of interleukin-2 receptor, Ia antigen and asialoGM1 antigen, measured by flowcytometry, was increased by contact with MMC. Growth inhibition of AH130, rat ascites hepatoma, and P815, murine mastocytoma, by Kupffer cells treated with anticancer drugs was greater than that by Kupffer cells alone or anticancer agent alone. These results show that MMC and ADM activate Kupffer cells, leading to synergistic antitumor activity. The results suggest that some anticancer agents act through immunological mechanisms as well as through direct antineoplastic activity.
- Published
- 1992
15. Hepatic macrophage malfunction in rats with obstructive jaundice and its biological significance
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Takayoshi Tobe, Naomi Funaki, Wenhai Zhang, Tetsu Sasaoki, Yukito Adachi, Masaharu Furutani, Shigeki Arii, Hiroaki Higashitsuji, Masahiro Mise, and Shinichi Fujita
- Subjects
Male ,medicine.medical_specialty ,Liver cytology ,medicine.medical_treatment ,Fluorescent Antibody Technique ,Dinoprostone ,Superoxide dismutase ,chemistry.chemical_compound ,Phagocytosis ,Superoxides ,Internal medicine ,Animals ,Medicine ,Macrophage ,Rats, Wistar ,Prostaglandin E2 ,Cholestasis ,Hepatology ,biology ,business.industry ,Superoxide ,Macrophages ,Jaundice ,Flow Cytometry ,Pathophysiology ,Rats ,Cytokine ,Endocrinology ,Liver ,chemistry ,biology.protein ,medicine.symptom ,business ,Interleukin-1 ,medicine.drug - Abstract
The present study was designed to investigate the pathophysiology of obstructive jaundice by analyzing the function of hepatic macrophages and their role in immune responses and homeostasis in rats. The phagocytic index, determined by the rate of disappearance of 51Cr-endotoxin from the peripheral blood after intravenous injection, was increased in obstructive jaundice 2 weeks after bile duct ligation. The superoxide production of isolated hepatic macrophages and peripheral blood monocytes, measured by the superoxide dismutase inhibitable ferricytochrome c reduction method, was increased. Prostaglandin E2 release, measured by RIA, was markedly increased in rats with obstructive jaundice, but there was no significant difference in interleukin-1 release between jaundiced and control rats. The flow-cytometric analysis of surface molecules of hepatic macrophages showed decreased expression of interleukin-2 receptor in rats with obstructive jaundice. Thus, the functions of hepatic macrophages in rats with obstructive jaundice were impaired. This malfunction may disturb the immunoregulatory network and metabolism, although the exact implications of the altered function of hepatic macrophages have not yet been clarified.
- Published
- 1992
16. Enhancement and hepatocyte-modulating effect of chemical mediators and monokines produced by hepatic macrophages in rats with induced sepsis
- Author
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Naomi Funaki, Shigeki Arii, Hiroaki Higashitsuji, Kazunobu Monden, Tetsu Sasaoki, Shigeyuki Itai, Yukito Adachi, and Takayoshi Tobe
- Subjects
Male ,medicine.medical_specialty ,Biology ,Dinoprostone ,Sepsis ,chemistry.chemical_compound ,Superoxides ,Internal medicine ,medicine ,Protein biosynthesis ,Animals ,Macrophage ,Tumor Necrosis Factor-alpha ,Superoxide ,Macrophages ,Monokines ,Rats, Inbred Strains ,General Medicine ,Metabolism ,Macrophage Activation ,medicine.disease ,Rats ,medicine.anatomical_structure ,Endocrinology ,Liver ,chemistry ,Protein Biosynthesis ,Hepatocyte ,Tumor necrosis factor alpha ,Hepatic dysfunction ,Interleukin-1 - Abstract
We investigated the production of chemical mediators by hepatic macrophages from rats with sepsis and the modulation of hepatocyte function by these hepatic macrophages. The chemical mediators we measured were superoxide (O 2 − ), TNF, IL-1, and PGE2. Production of these mediators by hepatic macrophages from rats with sepsis was significantly increased. Furthermore, protein synthesis by cultured hepatocytes was inhibited in a co-culture system of hepatocytes and hepatic macrophages from rats with sepsis, and it was even inhibited by the supernatant of cultured hepatic macrophages from septic rats. These results demonstrate that hepatic macrophages are activated in sepsis and may play a role in inducing hepatic dysfunction in sepsis.
- Published
- 1991
17. Enhancement of hepatic macrophages in septic rats and their inhibitory effect on hepatocyte function
- Author
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Shigeyuki Itai, Yukito Adachi, Naomi Funaki, Tetsu Sasaoki, Shigeki Arii, Kazunobu Monden, and Takayoshi Tobe
- Subjects
Lipopolysaccharides ,Male ,medicine.medical_specialty ,Hepatocyte function ,Biology ,Sepsis ,chemistry.chemical_compound ,Superoxides ,Internal medicine ,medicine ,Protein biosynthesis ,Animals ,Macrophage ,Inhibitory effect ,Cells, Cultured ,Superoxide ,Macrophages ,Zymosan ,Rats, Inbred Strains ,Opsonin Proteins ,medicine.disease ,In vitro ,Rats ,Endocrinology ,medicine.anatomical_structure ,Liver ,chemistry ,Protein Biosynthesis ,Hepatocyte ,Tetradecanoylphorbol Acetate ,Surgery - Abstract
In the present study, the function of hepatic macrophages and the modulation of hepatocytes by sepsis-elicited hepatic macrophages were investigated in rats with induced sepsis. The functional state of hepatic macrophages was determined by the following indicators: phagocytic index, protein-synthesizing capacity, and superoxide (O2-) producing capacity. These indices of changes in hepatic macrophages were much higher in rats with sepsis than in healthy controls. Moreover, the activated hepatic macrophages had some biological properties which were different from those of the resident Kupffer cells. It was found that protein synthesis by cultured hepatocytes was inhibited in the co-culture system of hepatocytes and sepsis-elicited hepatic macrophages, and that the supernatant of hepatic macrophages from rats with sepsis also reduced the protein-synthesizing capacity of cultured hepatocytes. Thus, activated hepatic macrophages may play a role in inducing hepatic dysfunction in sepsis.
- Published
- 1991
18. Depressed function of Kupffer cells in rats with CCl4-induced liver cirrhosis
- Author
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Naomi Funaki, Yukito Adachi, Takayoshi Tobe, Shigeyuki Itai, Tetsu Sasaoki, Shigeki Arii, Hiroaki Higashitsuji, and Kazunobu Monden
- Subjects
Male ,medicine.medical_specialty ,Pathology ,Cirrhosis ,Kupffer Cells ,Endocytic cycle ,CCL4 ,Biology ,Liver Cirrhosis, Experimental ,Superoxide dismutase ,chemistry.chemical_compound ,Superoxides ,Internal medicine ,medicine ,Animals ,Distribution (pharmacology) ,Carbon Tetrachloride ,Superoxide Dismutase ,Superoxide ,Kupffer cell ,Rats, Inbred Strains ,General Medicine ,Opsonin Proteins ,medicine.disease ,Endocytosis ,Rats ,Endotoxins ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Carbon tetrachloride ,biology.protein - Abstract
In the present study, the Kupffer cell function of rats with CCl4-induced liver cirrhosis was tested by analyzing the changes in the host defense system. In rats without liver cirrhosis injected with CCl4 for 3 weeks concomitant with the high opsonic activity the endocytic index was significantly increased. Rats treated for 9 and 13 weeks developed cirrhosis, and their endocytic indices were not increased despite the rise in their opsonic activity. Particularly, the endocytic index of 13-week-treated rats with advanced liver cirrhosis was significantly lower than that of the other groups. The organic distribution of 51Cr-endotoxin injected intravenously exhibited characteristic changes in 9-week- and 13-week-treated rats: decreased hepatic uptake and increased splenic uptake. In contrast, pulmonary uptake was increased in all CCl4-treated rats. The superoxide production by Kupffer cells from 13-week-treated rats was greatly reduced, accompanied by the decreased superoxide dismutase activity of liver homogenate. Thus, results of this study suggest that Kupffer cell dysfunction is one of the main factors affecting host defenses in liver cirrhosis.
- Published
- 1990
19. Etiology and clinical study of community-acquired pneumonia in 157 hospitalized children
- Author
-
Yasuo Kondo, Yukishige Yanagawa, Naomi Funaki, Eiichi Nakayama, Hiroaki Ito, Yuri Kodaka, Mei Momomura, Hirokazu Kutsuma, Fumie Hirai, Taketoshi Iitsuka, Tajima T, and Kimiko Ubukata
- Subjects
Microbiology (medical) ,Male ,medicine.medical_specialty ,Bacteremia ,medicine.disease_cause ,Patient Admission ,Community-acquired pneumonia ,Japan ,Internal medicine ,Streptococcus pneumoniae ,medicine ,Humans ,Pharmacology (medical) ,Mycoplasma Infections ,Serologic Tests ,Practice Patterns, Physicians' ,Child ,Retrospective Studies ,business.industry ,Bacterial pneumonia ,Clindamycin ,Infant ,Pneumonia ,Chlamydia Infections ,medicine.disease ,Anti-Bacterial Agents ,Community-Acquired Infections ,Infectious Diseases ,C-Reactive Protein ,Concomitant ,Child, Preschool ,Immunology ,Etiology ,Female ,business ,Parainfluenza-3 ,medicine.drug - Abstract
We tried to verify whether the currently employed diagnosis and treatment of community-acquired pneumonia in children were appropriate. For this purpose, we created tentative criteria for the classification of pediatric community-acquired pneumonia. We classified the community-acquired pneumonia into ten categories: (1) bacterial, (2) concomitant viral-bacterial, (3) viral, (4) mycoplasmal, (5) concomitant mycoplasmal-bacterial, (6) concomitant mycoplasmal-viral, (7) chlamydial, (8) concomitant chlamydial-bacterial, (9) concomitant chlamydial-viral, and (10) unknown. Children aged 1 month to 13 years with radiographic and clinical evidence of pneumonia were enrolled. Between October 2001 and September 2002, we enrolled 165 patients. The etiologic agents were determined in 126 of the 157 (80.3%) patients who were finally diagnosed with pneumonia. Two blood cultures were positive for Haemophilus influenzae type b and Streptococcus pneumoniae. A viral infection alone was found in 28 of the 157 patients (17.8%), a bacterial (without mycoplasmal) alone infection in 42 (26.8%), a concomitant viral-bacterial infection in 28 (17.8%), and a mycoplasmal infection in 27 (17.2%) patients. RS virus was identified in 28 patients (17.8%), influenza A in 12 (7.6%), parainfluenza 3 in 8 (5.1%), adenovirus in 8 (5.1%), and influenza B and measles virus in 1 patient each. Streptococcus pneumoniae was the most common cause of bacterial pneumonia. We chose the initial treatment according to clinical and laboratory findings on admission (i.e., patients' age, clinical course, chest X-ray, and laboratory findings). In 68 of the 71 patients with bacterial (without mycoplasmal) pneumonia, an appropriate antibacterial-agent was prescribed. In 25 of the 27 patients with mycoplasmal pneumonia, clindamycin and minocycline were prescribed.
- Published
- 2006
20. Primary pancreatic plasmacytoma
- Author
-
Yasunori Deguchi, Kazuhiko Mizuta, Atsushi Nonaka, Yukihiro Kono, Naomi Funaki, and Eiji Takeuchi
- Subjects
Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Plasma cell ,CD38 ,Immunoglobulin light chain ,Granuloma, Plasma Cell ,Diagnosis, Differential ,Pancreatectomy ,immune system diseases ,Pancreatic mass ,Medicine ,Humans ,Lymph node ,business.industry ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Staining ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Oncology ,Lymphatic Metastasis ,Splenectomy ,Plasmacytoma ,Lymph ,business ,Tomography, X-Ray Computed ,Tomography, Emission-Computed - Abstract
We report an extremely rare case of primary pancreatic plasmacytoma. A 56-year-old man had a 4-cm mass in the pancreatic tail and received distal pancreatectomy. This mass mainly consisted of plasma cells, but we failed to demonstrate their monoclonality in spite of the immunohistological staining. One and a half years later, this patient's right inguinal node swelled, and this node also showed a dense plasma cell infiltration. A very precise immunohistological staining was performed for this lymph node and the previous pancreatic mass, and both were diffusely positive for kappa light chain, IgG, and CD38. In the absence of myeloma elsewhere, we thus reached the correct diagnosis of primary pancreatic plasmacytoma, which later metastasized to lymph nodes. In the presence of the plasma cell proliferation in a pancreatic mass, plasmacytoma should be taken into consideration, and a more careful immunohistological staining is definitely necessary.
- Published
- 2004
21. Combination of α-fetoprotein mRNA-based detection of hematogenously disseminating hepatocellular carcinoma cells and analysis of cancer cell membrane fluidity is more accurate in screening patients at risk of postoperative recurrence
- Author
-
Atsushi Nonaka, Jeon-Uk Lee, Junji Tanaka, Naomi Funaki, Yukihiro Kono, Masayuki Imamura, and Fumiaki Yotsumoto
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,business.industry ,Cell ,Cancer ,General Medicine ,Cell cycle ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Hepatocellular carcinoma ,Cancer cell ,Carcinoma ,medicine ,Membrane fluidity ,business ,Oncofetal antigen - Abstract
We developed an mRNA-based, highly specific and sensitive method to detect hepatocellular carcinoma cells present in blood. However, the reason for some patients being positive for blood analysis and negative for recurrence has yet to be found. We recently established a method to measure membrane fluidity of hepatocellular carcinoma cells, and used it to analyze the actual membrane fluidity of human hepatocellular carcinoma cells. We found that patients with carcinoma cells with lower membrane fluidity less frequently developed recurrence. The analysis of both membrane fluidity and alpha-fetoprotein mRNA thus greatly increased the accuracy of the prediction of postoperative recurrence.
- Published
- 2004
22. Combination of alpha-fetoprotein mRNA-based detection of hematogenously disseminating hepatocellular carcinoma cells and analysis of cancer cell membrane fluidity is more accurate in screening patients at risk of postoperative recurrence
- Author
-
Naomi, Funaki, Junji, Tanaka, Yukihiro, Kono, Atsushi, Nonaka, Fumiaki, Yotsumoto, Jeon-Uk, Lee, and Masayuki, Imamura
- Subjects
Carcinoma, Hepatocellular ,DNA, Complementary ,Cell Membrane ,Liver Neoplasms ,Prognosis ,Polymerase Chain Reaction ,Treatment Outcome ,Liver ,Microscopy, Fluorescence ,Recurrence ,Cell Line, Tumor ,Humans ,RNA ,RNA, Messenger ,alpha-Fetoproteins - Abstract
We developed an mRNA-based, highly specific and sensitive method to detect hepatocellular carcinoma cells present in blood. However, the reason for some patients being positive for blood analysis and negative for recurrence has yet to be found. We recently established a method to measure membrane fluidity of hepatocellular carcinoma cells, and used it to analyze the actual membrane fluidity of human hepatocellular carcinoma cells. We found that patients with carcinoma cells with lower membrane fluidity less frequently developed recurrence. The analysis of both membrane fluidity and alpha-fetoprotein mRNA thus greatly increased the accuracy of the prediction of postoperative recurrence.
- Published
- 2004
23. Successive cultures of mature hepatocytes for hepatocyte autotransplantation to assist liver function after liver resection for cancer
- Author
-
Naomi Funaki, Junji Tanaka, Atsushi Nonaka, Gakuji Ohshio, Taketoshi Sugiyama, Fumiaki Yotsumoto, Masayuki Imamura, and Tomoharu Sugie
- Subjects
Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Cell Transplantation ,medicine.medical_treatment ,Cell Culture Techniques ,Mitosis ,Spleen ,Cell Separation ,Biology ,Transplantation, Autologous ,Albumins ,medicine ,Animals ,Humans ,Microscopy, Phase-Contrast ,Rats, Wistar ,Cells, Cultured ,Oncogene ,Liver Neoplasms ,Cancer ,General Medicine ,medicine.disease ,Autotransplantation ,Rats ,Transplantation ,medicine.anatomical_structure ,Oncology ,Liver ,Cell culture ,Hepatocyte ,Hepatocytes ,Liver function ,Glycogen ,Immunosuppressive Agents - Abstract
We developed a method for the rapid successive cultures of adult rat mature hepatocytes on plastic dishes while avoiding viral transformation or co-culture with other cell lines. This method also allows for culturing adult human mature hepatocytes up to the secondary culture. These can be expected to provide a good source for hepatocyte autotransplantation, and, combined with the previously reported methods for the transplantation of hepatocytes into the spleen, a promising option for the support of liver function after liver resection for cancer without the need for immunosuppressive agents.
- Published
- 2002
24. Membrane fluidity correlates with liver cancer cell proliferation and infiltration potential
- Author
-
Yoshihisa Takeda, Naomi Funaki, Gakuji Ohshio, Junji Tanaka, Taketoshi Sugiyama, Atsushi Nonaka, Fumiaki Yotsumoto, Mitsuaki Kohmoto, and Masayuki Imamura
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Membrane Fluidity ,Cell ,Fluorescence Polarization ,Biology ,Models, Biological ,medicine ,Membrane fluidity ,Tumor Cells, Cultured ,Humans ,Microscopy, Phase-Contrast ,Oncogene ,Cell growth ,Cell Membrane ,Liver Neoplasms ,Cancer ,General Medicine ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Bromodeoxyuridine ,Cancer cell ,Cancer research ,Liver cancer ,Infiltration (medical) ,Cell Division - Abstract
We developed a method to measure membrane fluidity of living cancer cells in two- and three-dimensional cultures, and found that there was a close relationship between the membrane fluidity of cancer cells and their proliferative and infiltrative ability. Membrane fluidity is thus a promising indicator of the probability of cancer recurrence.
- Published
- 2001
25. Perioperative quantitative analysis of cytokeratin 20 mRNA in peripheral venous blood of patients with colorectal adenocarcinoma
- Author
-
Naomi Funaki, Gakuji Ohshio, Junji Tanaka, Fumiaki Yotsumoto, Masayuki Imamura, M Furutani, Atsushi Nonaka, and Taketoshi Sugiyama
- Subjects
Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Colorectal cancer ,Keratin-20 ,Adenocarcinoma ,Metastasis ,Cytokeratin ,Intermediate Filament Proteins ,Predictive Value of Tests ,Recurrence ,medicine ,Biomarkers, Tumor ,Humans ,RNA, Messenger ,Neoplasm Metastasis ,Vein ,Aged ,Aged, 80 and over ,business.industry ,Keratin 20 ,General Medicine ,Venous blood ,Perioperative ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Female ,business ,Colorectal Neoplasms - Abstract
Hematogenous dissemination is a significant short-coming of colorectal carcinoma treatment. To screen patients with high risk for such blood-borne metastasis, we previously developed a highly sensitive system for the detection of cytokeratin 20 (CK-20) mRNA in blood. For a more practical application, we improved this system by making it quantitative and capable of analyzing peripheral venous blood for the detection of perioperative changes in CK-20 mRNA. CK-20 mRNA was not always detected in the preoperative blood, even in patients in an advanced stage, but it was identified without fail in intra- and post-operative blood. In addition, more copies of CK-20 mRNA were observed in the intra-operative blood than in pre- and post-operative blood. This study suggests that analysis of perioperative changes may provide important information for the precise evaluation of hematogenous dissemination and of the effect of surgical maneuvers on recurrence.
- Published
- 2000
26. Quantitative analysis of alpha-fetoprotein mRNA in circulating peripheral blood of patients with hepatocellular and alpha-fetoprotein-producing gastric carcinomas
- Author
-
Naomi Funaki, Junji Tanaka, and Masayuki Imamura
- Subjects
Pathology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,medicine.medical_treatment ,Biology ,Polymerase Chain Reaction ,General Biochemistry, Genetics and Molecular Biology ,Stomach Neoplasms ,medicine ,Humans ,RNA, Messenger ,General Pharmacology, Toxicology and Pharmaceutics ,Chemotherapy ,Micrometastasis ,Liver Neoplasms ,Cancer ,General Medicine ,Venous blood ,Perioperative ,medicine.disease ,digestive system diseases ,Reverse transcriptase ,Hepatocellular carcinoma ,alpha-Fetoproteins ,Neoplasm Recurrence, Local ,Alpha-fetoprotein - Abstract
In conjunction with strategies introduced in recent years to identify cancer micrometastasis through amplification of cancer-associated mRNA, we developed a highly sensitive system to detect alpha-fetoprotein mRNA in circulating peripheral blood of hepatocellular carcinoma patients. The aim of the present study was to make our original system quantitative. Peripheral venous blood from patients with hepatocellular carcinoma and alpha-fetoprotein-producing gastric carcinoma was subjected to reverse transcription followed by our original three-step polymerase chain reaction co-amplifying both the original sequence and our synthetic competitor. We succeeded in modifying our system for quantitative analysis, and investigated the perioperative change, the postoperative change and the change after chemotherapy in order to illustrate the possible application of this method. The quantitative analysis of alpha-fetoprotein mRNA present in the peripheral blood represents a useful tool for analyzing the relationship of surgery to recurrence, the effect of chemotherapy, and to predict impending recurrence in patients with hepatocellular and alpha-fetoprotein-producing gastric carcinomas.
- Published
- 1998
27. Hematogenous spreading of hepatocellular carcinoma cells: possible participation in recurrence in the liver
- Author
-
Naomi Funaki, Masayuki Imamura, Junji Tanaka, Shin-ichi Seto, Toshimi Kaido, and Takayuki Kasamatsu
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cell ,Premises ,law.invention ,law ,medicine ,Humans ,RNA, Messenger ,neoplasms ,Polymerase chain reaction ,Aged ,Messenger RNA ,Lung ,Hepatology ,business.industry ,Liver Neoplasms ,Middle Aged ,medicine.disease ,digestive system diseases ,Peripheral blood ,Neoplasm Proteins ,medicine.anatomical_structure ,Hepatocellular carcinoma ,Female ,alpha-Fetoproteins ,Neoplasm Recurrence, Local ,business ,Immunostaining - Abstract
To detect hepatocellular carcinoma (HCC) cells in the circulating peripheral blood, we previously designed a highly sensitive reverse-transcription polymerase chain reaction (RT-PCR) method targeting alpha-fetoprotein (AFP) messenger RNA (mRNA). Using this method, we analyzed peripheral blood of in- and out-patients bearing HCC for 2 months consecutively and examined the outcome thereafter. All 11 patients with recurrence either in the liver alone or in both the liver and the lung were positive for AFP mRNA. Among 10 recurrence-free patients, 2 patients were AFP mRNA-negative and remained recurrence-free during a period of 22 months observed. Four of 8 AFP mRNA-positive, recurrence-free patients developed a clinically evident recurrence in the liver after 2 to 16 months. Seven of 8 preoperative patients were already positive for AFP mRNA and the remaining negative patient became positive during surgery. Four of 6 preoperatively positive and still-alive patients had recurrence in the liver after 2 to 9 months. None of the HCC-negative patients were positive for AFP mRNA. We actually found an AFP protein-positive cell in peripheral blood obtained from one of the AFP mRNA-positive patients by immunostaining. The present results suggest that circulating HCC cells may have some relationship with the recurrence of HCC in the liver.
- Published
- 1997
28. Effects of cholecystokinin and carbachol on membrane fluidity in pancreatic acini
- Author
-
Noriyuki Okada, Masayuki Imamura, Toshiro Tanaka, Junji Tanaka, Masanori Yoshida, Naomi Funaki, Gakuji Ohshio, Tetsu Sasaoki, Takashi Imamura, Shigeki Arii, Zhao-hui Wang, and Mitsuaki Kohmoto
- Subjects
Male ,medicine.medical_specialty ,Carbachol ,Physiology ,Membrane Fluidity ,Biology ,digestive system ,Cholecystokinin receptor ,Sincalide ,Secretin ,chemistry.chemical_compound ,Hormone Antagonists ,Internal medicine ,medicine ,Membrane fluidity ,Animals ,Rats, Wistar ,Pancreas ,Cholecystokinin ,Dose-Response Relationship, Drug ,L-Lactate Dehydrogenase ,Gastroenterology ,Bombesin ,medicine.disease ,Rats ,medicine.anatomical_structure ,Endocrinology ,Proglumide ,chemistry ,Pancreatitis ,Phosphatidylcholines ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
The effects of pancreatic secretagogues on the membrane fluidity of pancreatic acini were investigated using 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene iodide as a probe. Two kinds of pancreatic secretagogues, one category of which induces acute pancreatitis (cholecystokinin and carbachol) and another which does not induce acute pancreatitis (bombesin, CCK-JMV-180, and secretin), as well as lecithin were used to investigate the effect of changes in membrane fluidity of acini. Our study revealed that the membrane fluidity of the pancreatic acini was unaffected by a physiological dose (10(-11) M) of cholecystokinin. However, stimulation with a supramaximal dose of cholecystokinin (10(-8) M) increased membrane fluidity markedly within 20 min. Membrane fluidity increased dose-dependently with increasing CCK stimulation. A supramaximal dose of cholecystokinin also induced bleb formation and increased LDH release. These phenomena were blocked by simultaneous incubation with CR1505 (Loxiglumide), a potent antagonist of peripheral cholecystokinin receptors. A supramaximal dose of carbachol (10(-3) M) also induced increases in the membrane fluidity. Pancreatic secretagogues that do not induce acute pancreatitis did not induce alterations in membrane fluidity. Lecithin increased both membrane fluidity and LDH release. These observations suggest that this increase in membrane fluidity of the pancreatic acini may be related to membrane alteration and to functional damage of the acini. These observations [correction of observation] can serve as a window to detect the development of acute pancreatitis at an early stage.
- Published
- 1996
29. HLA-DR antigen and interleukin-2 receptor expression on primary-cultured human hepatic macrophages in relation to liver cirrhosis and hepatitis virus infection
- Author
-
Kazunobu Monden, Junji Tanaka, Naomi Funaki, Shigeki Arii, and Masayuki Imamura
- Subjects
Interleukin 2 ,Liver Cirrhosis ,Male ,Cirrhosis ,Hepatitis, Viral, Human ,Receptor expression ,General Biochemistry, Genetics and Molecular Biology ,Antigen ,medicine ,Humans ,IL-2 receptor ,General Pharmacology, Toxicology and Pharmaceutics ,Receptor ,Cells, Cultured ,Aged ,Hepatitis ,Aged, 80 and over ,business.industry ,Macrophages ,Cell Membrane ,Receptors, Interleukin-2 ,General Medicine ,HLA-DR Antigens ,Middle Aged ,medicine.disease ,Liver ,Immunology ,Female ,business ,Viral hepatitis ,medicine.drug - Abstract
We analyzed primary-cultured human hepatic macrophages (HHMphi) from 12 patients with non-cirrhotic and cirrhotic livers for cell surface expression of HLA-DR antigen and interleukin-2 receptor (IL-2R). Compared to the relatively abundant HLA-DR antigen, IL-2R expression was generally low. No significant difference was observed between HLA-DR antigen expression nor IL-2 receptor expression. HHMphi from patients with serum hepatitis viral markers, however, expressed significantly more HLA-DR antigen than did HHMphi of patients without viral markers, which suggest a possible role of HHMphi as antigen-presenting cells (APC) in viral hepatitis. This direct, quantitative measurement of cell surface molecule expression on hepatic macrophages of human may provide an important clue to the pathophysiology of human liver disorders.
- Published
- 1996
30. Participation of hepatic macrophages and plasma factors in endotoxin-induced liver injury
- Author
-
Masayuki Imamura, Masahiro Mise, Masaharu Furutani, Satoshi Ishiguro, Toshio Nakamura, Shigeki Arii, Shinichi Fujita, Naomi Funaki, Kazunobu Monden, Yukito Adachi, Tadahiro Kitao, and Hiroaki Higashitsuji
- Subjects
Lipopolysaccharides ,Male ,medicine.medical_specialty ,Gadolinium ,Biology ,Lesion ,Internal medicine ,medicine ,Animals ,Aspartate Aminotransferases ,RNA, Messenger ,Rats, Wistar ,Lactate ringer ,Liver injury ,L-Lactate Dehydrogenase ,Tumor Necrosis Factor-alpha ,Liver Diseases ,Macrophages ,Heparin ,Lactate dehydrogenase.serum ,medicine.disease ,Rats ,Endotoxins ,Endocrinology ,Liver ,Toxicity ,Immunology ,Surgery ,Tumor necrosis factor alpha ,medicine.symptom ,Chemical and Drug Induced Liver Injury ,Perfusion ,medicine.drug - Abstract
The present study was designed to investigate the mechanism responsible for endotoxin-induced liver injury, based on the working hypothesis that hepatic macrophages activated by endotoxin play a key role in the development of this injury. At both the protein and the transcription levels, the intravenous administration of endotoxin was shown to have increased the capacity of hepatic macrophages to produce chemical mediators. To inhibit the function of hepatic macrophages, gadolinium chloride (GdCl3), a specific inhibitor of resident hepatic macrophages, was preadministered to rats before endotoxin injection. GdCl3 reduced the elevated glutamic oxaloacetic transamiase and lactate dehydrogenase serum levels produced by endotoxin treatment, suppressed the increased mRNA expression of tumor necrosis factor (TNF-α) produced in liver nonparenchymal cells by endotoxin, and then improved the survival rate of lipopolysaccharide-injected rats. These results indicated that hepatic macrophages played a crucial role in liver injury and that TNF-α was the most likely factor implicated in the development of endotoxin-induced liver injury. Furthermore, we found that liver injury did not progress during perfusion of endotoxin-pretreated extirpated liver with lactate Ringer's solution, whereas liver perfused with plasma developed remarkable hepatic impairment, which was inhibited almost completely by GdCl3-pretreatment; moreover, addition of heparin to the perfusate also prevented this deterioration. Thus, the present study showed that the activation of hepatic macrophages and factors in the plasma were two essential elements in the occurrence and development of endotoxin-induced liver injury.
- Published
- 1995
31. Alteration in the fluorescence polarization of rat plasma and liver cell membranes following bile duct ligation in rats
- Author
-
Ken-Ichi Fujita, Junji Tanaka, Toshimi Kaido, Masayuki Imamura, Takayuki Kasamatsu, Wang Ben Zhong, Masanori Yoshida, Naomi Funaki, and Mitsuaki Komoto
- Subjects
medicine.medical_specialty ,Bilirubin ,Membrane Fluidity ,medicine.medical_treatment ,Fluorescence Polarization ,digestive system ,chemistry.chemical_compound ,Internal medicine ,medicine ,Membrane fluidity ,Animals ,Hepatectomy ,Rats, Wistar ,business.industry ,Liver cell ,Bile duct ligation ,Cell Membrane ,General Medicine ,Jaundice ,Cholestasis, Extrahepatic ,digestive system diseases ,Liver Regeneration ,Rats ,Membrane ,Endocrinology ,chemistry ,Liver ,Surgery ,medicine.symptom ,business ,Fluorescence anisotropy - Abstract
The fluorescence polarization levels of liver cell membranes and plasma were analyzed to determine membrane fluidity following bile duct ligation (BDL) in rats. Fluorescence polarization was measured with a spectrofluorophotometer equipped with polarizers, using 1,6-diphenyl-1,3,5-hexatrien (DPH) as a probe. After bile duct ligation, liver cell membrane fluidity decreased significantly for up to 14 days after surgery (P0.001 on 3rd and 7th days). The polarization of the plasma in rats with BDL slightly but significantly increased compared to the levels in the control animals over the 14-day period following BDL. In addition, a small but significant correlation in the polarization levels between plasma and liver cell membranes (r = 0.362, P0.02) was observed. The co-incubation of BDL plasma with normal liver cell membranes resulted in a decrease in membrane fluidity, which suggested that BDL rat plasma had a direct effect on membrane fluidity. After a 70% hepatectomy, the polarization of the membranes from remnant livers in the BDL rats remained elevated relative to the sham-operated controls. It is thus concluded that the membrane fluidity of the livers in BDL rats decreases following bile duct ligation and does not increase after a 70% hepatectomy, presumably due to the increased plasma level of bilirubin.
- Published
- 1995
32. Chemical mediator release and surface marker expression of hepatic macrophages in rats with CCl4-induced liver cirrhosis
- Author
-
Shigeki Arii, Hiroaki Higashitsuji, Tetsu Sasaoki, Junji Tanaka, Masayuki Imamura, Kazunobu Monden, Naomi Funaki, and Yukito Adachi
- Subjects
Male ,medicine.medical_specialty ,Cirrhosis ,Cell Survival ,medicine.medical_treatment ,CCL4 ,Cell Separation ,G(M1) Ganglioside ,Biology ,Liver Cirrhosis, Experimental ,General Biochemistry, Genetics and Molecular Biology ,Dinoprostone ,chemistry.chemical_compound ,Antigen ,Phagocytosis ,Internal medicine ,medicine ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,Rats, Wistar ,Receptor ,Cells, Cultured ,Carbon Tetrachloride Poisoning ,Tumor Necrosis Factor-alpha ,Macrophages ,Histocompatibility Antigens Class II ,Interleukin ,Receptors, Interleukin-2 ,General Medicine ,medicine.disease ,Rats ,Endocrinology ,chemistry ,Liver ,Antigens, Surface ,Carbon tetrachloride ,Tumor necrosis factor alpha ,Prostaglandin E ,Interleukin-1 - Abstract
The present study was performed to analyze possible functional alterations of hepatic macrophages (HMΦ) in rats with carbon tetrachloride (CCl 4 )-induced liver cirrhosis. HMΦ from rats injected with CCl 4 for 13 weeks and cultured for 24 hours released less than normal amounts of prostaglandin E 2 (PGE 2 ) and tumor necrosis factor (TNF) and very large amounts of interleukin-1 (IL-1). In rats injected with CCl 4 for 9 weeks, only PGE 2 production was reduced. Interleukin-2 receptor (IL-2R), Ia antigen and asialo GM 1 antigen expressions of HMΦ from both the 9- and 13-week groups were significantly decreased. IL-2R and Ia antigen expressions showed larger decreases in the 13-week group. Thus, it is concluded that HMΦ derived from CCl 4 -induced cirrhotic livers show a functional alteration in the release of cytokines (except for IL-1) and a decrease in surface marker expression, as cirrhosis advances. These results should provide a basis for further investigation into the host-compromised status in the presence of liver cirrhosis.
- Published
- 1994
33. Chemical mediators released from hepatic macrophages in primary culture--basic characteristics of human hepatic macrophages and changes in liver cirrhosis
- Author
-
Takayoshi Tobe, Naomi Funaki, Tetsu Sasaoki, Junji Tanaka, Kazunobu Monden, Yukito Adachi, Hiroaki Higashitsuji, Shigeki Arh, and Shigeyuki Itai
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,Carcinoma, Hepatocellular ,Liver cytology ,Cell Survival ,Cell Separation ,Dinoprostone ,chemistry.chemical_compound ,Reference Values ,Stomach Neoplasms ,Superoxides ,Internal medicine ,Medicine ,Macrophage ,Humans ,Cells, Cultured ,business.industry ,Superoxide ,Macrophages ,Zymosan ,Liver Neoplasms ,Metabolism ,medicine.disease ,Pathophysiology ,Kinetics ,Endocrinology ,chemistry ,Liver ,Cell culture ,Immunology ,Colonic Neoplasms ,Surgery ,business ,Interleukin-1 - Abstract
Chemical mediators released from human hepatic macrophages (HHM phi) in primary cultures were analyzed for their secretory function and probable contribution to the modulation of the host defense system and metabolism in liver cirrhosis. In our basic studies, HHM phi increased dose dependently the release of superoxide (O2-) and interleukin-1 (IL-1) when stimulated by opsonized zymosan, up to 1000 micrograms/dish. PGE2 production showed a relatively narrow range of dose dependency, and larger doses led to a reduction of PGE2 yield in some samples. Next, we compared the mediator release from the HHM phi of patients with liver cirrhosis with that from HHM phi in normal liver. O2- released from HHM phi of 8 patients with liver cirrhosis was significantly decreased (controls, n = 20) (P < 0.01). IL-1 released from the HHM phi of 6 cirrhotic patients tended to be higher than that from the HHM phi of 10 control patients, but the difference was not statistically significant (P < 0.10). PGE2 production, however, was about the same in the two groups. These results suggest that cultured HHM phi have certain basic characteristics in releasing mediators with highly potent specific activities and also that these secretory abilities may change in liver cirrhosis. In conclusion, the analysis of cultured HHM phi may be a very practical way to clarify their inherent abilities and participation in the complicated clinical features of liver cirrhosis.
- Published
- 1993
34. A case report of the cloacogenic cyst of the retrorectal space
- Author
-
Keizo Kimura, Osamu Kitamura, Motokazu Asano, Akikazu Yoshida, Hideki Noda, Naomi Funaki, and Masao Matsumoto
- Subjects
business.industry ,Gastroenterology ,Medicine ,Surgery ,Cyst ,Anatomy ,Space (mathematics) ,business ,medicine.disease - Published
- 1987
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