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Biomedical subjects

Y Arima

Publications and source records attributed to Y Arima.

At least 19 recordsLinked to original sources

Serine protease Omi/HtrA2 targets WARTS kinase to control cell proliferation.

The serine protease Omi/HtrA2 was initially regarded as a proapoptotic molecule that proteolyses several proteins to induce cell death. Recent studies, however, indicate that loss of Omi protease activity increases susceptibility to stress-induced cell death. These complicated findings suggest that the protease activity of Omi is involved not only in apoptosis but also in cellular homeostasis. However, the targets which Omi uses to mediate this novel process are unknown. Previously, we showed that WARTS (WTS)/large tumor-suppressor 1 mitotic kinase interacts with the protein/discs-large protein/zonula (PDZ) domain of Omi and promotes its protease activity. We now report that WTS is a substrate for Omi protease activity, thus it is not only a regulator but also a downstream target of this protease. Interaction with Omi PDZ domain is required for WTS to be proteolysed. When caspase-9-deficient mouse embryonic fibroblasts (MEFs) were treated with staurosporine, WTS was proteolysed by activated endogenous Omi without induction of cell death. Therefore, protease activity of Omi and proteolysis of WTS are not necessarily required for cell death. We found that depletion of Omi from HeLa cells results in accelerated cell proliferation despite no significant change in the duration of mitosis. The depletion of WTS showed the same effect on S phase progression. Therefore, WTS proteolytic fragment(s) generated by Omi may act as an inhibitor of G1/S progression. Our data reveal a role for Omi-mediated processing of WTS in negative regulation of cell cycle progression at interphase, suggesting a novel function of Omi other than apoptosis.

Animals↗

Splenic artery embolization before laparoscopic splenectomy in children.

BACKGROUND: This study assessed the safety and utility of preoperative splenic artery embolization before laparoscopic splenectomy in children. METHODS: Five young girls with a mean age of 13.2 years underwent laparoscopic splenectomies at the authors' institution from August 1998 to April 2003. Three of the patients had idiopathic thrombocytopenic purpura, and two had hereditary spherocytosis. Preoperative splenic artery embolization was performed the day before the surgery in all cases. The laparoscopic splenectomy was performed using traditional laparoscopic procedures and standard laparoscopic instruments with the patient in the right semilateral position. RESULTS: The mean spleen weight was 252.6 g, and the mean length was 11.6 cm. All the patients reported postembolic pain, but not to a level unmanageable by intravascular narcotics. There were no severe complications in the splenic artery embolization. The laparoscopic splenectomies were completed in a mean of 211 min, with a mean estimated blood loss of 9 ml. None of the operations required conversion to traditional open laparotomy, and none of the patients died or experienced operative complications. CONCLUSION: The authors concluded that splenic artery embolization is safe and useful as an adjuvant procedure performed before elective laparoscopic splenectomy in children.

Adolescent↗

Impaired removal of 8-hydroxydeoxyguanosine induced by UVB radiation in naevoid basal cell carcinoma syndrome cells.

BACKGROUND: The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by tumorigenesis such as multiple basal cell carcinomas, odontogenic keratocysts and developmental abnormalities such as calcified dural folds and rib-anomalies. Recently, it has been shown that ultraviolet (UV) B exposure produced more BCCs in ptch knockout mice than wild mice. OBJECTIVES: To Investigate the role of UV in development of BCCs in NBCCS, cellular sensitivity to killing by UVB and removal of UVB-induced oxidative DNA damage were examined using fibroblasts derived from patients with NBCCS under physiologically relevant doses of UVB exposure. PATIENTS AND METHODS: Three patients with NBCCS, a 59-year-old male patient, an 18-year-old boy and a 13-year-old boy were examined by photobiological analysis. Cellular sensitivity to killing by UVB and UVC and removal of oxidative DNA damage caused by UVB were tested using fibroblasts derived from these patients. We measured cellular 8-hydroxydeoxyguanosine (8-OHdG) after UVB exposure up to 24 h after UVB exposure using high-performance liquid chromatography. RESULTS: All three cell strains derived from the patients with NBCCS were hypersensitive to killing by UVB (D10: 50-70% of normal) but not by UVC. After UVB exposure, the production of 8-OHdG increased dose dependently up to 3200 J m-2 in both NBCCS cells and normal cells. In normal cells, 8-OHdG after UVB exposure returned to its basal level during 24 h, whereas in NBCCS cells the amount of 8-OHdG after 800 J m-2 of UVB exposure did not return to its basal level even after 24 h. The result indicates the removal of 8-OHdG could be impaired in NBCCS cells. Ability in removal of thymine dimers of NBCCS cells was similar to that of normal cells. CONCLUSIONS: Hypersensitivity to UVB can be one of the diagnostic tools of NBCCS for those whose clinical features have not yet completed. Hypersensitivity to cell killing and the impairment of removal of 8-OHdG after UVB exposure may play some role in developing BCCs and other tumours in NBCCS.

8-Hydroxy-2'-Deoxyguanosine↗

Hand-assisted laparoscopic hepatectomy after partial splenic embolization.

The case of a patient with hepatocellular carcinoma and thrombocytopenia secondary to liver cirrhosis who underwent successful hand-assisted laparoscopic hepatectomy after partial splenic embolization is described. A 67-year-old man with severe liver cirrhosis was admitted for treatment of hepatocellular carcinoma. His early phase of hepatic angiography showed two hypervascular tumors in segment 6. The patients liver function was poor, with the indocyanine green retention at 15 min of 49.5%, a total serum bilirubin concentration of 2.0 mg/dl, an albumin concentration of 2.8 g/dl, and an hyaluronic acid concentration of 649 ng/ml. The platelet count was 3.0 x 10(4)/microl secondary to hypersplenism. Partial splenic embolization decreased the splenic volume by 50% preoperatively. At 2 months later, the platelet count was 6.0 x 10(4)/microl, and hand-assisted laparoscopic partial hepatectomy was performed uneventfully. The patients postoperative course was unremarkable, and he was discharged on postoperative day 12.

Aged↗

A case of adenoid cystic carcinoma (ACC) of the breast and review of the utility of preoperative imaging diagnose.

A case of adenoid cystic carcinoma (ACC) of the breast in a 66-year-old woman is reported herein. ACC accounts for about 0.1% of all breast cancers. Our patient presented with a small, elastic and hard mass, measuring 2.0x2.0 cm, between both outer quadrants of the right breast. Although physical examination, ultrasonography and magnetic resonance (MR) mammography suggested a benign tumor, aspiration biopsy cytology (ABC) was performed twice, and the second ABC specimen was evaluated as suspicious for breast carcinoma. Breast conserving surgery with a level II lymph node dissection was subsequently performed. There was no lymph node metastases and estrogen receptor (ER) status was negative. Light microscopy revealed various growth patterns, with the cells showing biphasic cellularity. According to immunohistochemical analyses, CEA, actin and vimentin were positive, S-100 protein was negative, and the cytokeratin reaction was partially positive. Therefore, ACC of the breast was diagnosed. Although ACC of the breast is a rare neoplasm, it should be considered in the differential diagnosis even if various diagnostic imaging studies suggest a benign tumor of the breast. Awareness of this tumor will help prevent misdiagnosis.

Actins↗

Microsatellite instability and alternative genetic pathway in intrahepatic cholangiocarcinoma.

BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (ICC) arises from intrahepatic bile duct epithelium and is the second most prevalent among primary liver cancers. The aim of this study was to clarify the mechanism of cholangiocarcinogenesis. METHODS: We studied the incidence of microsatellite instability (MSI) involving eight highly polymorphic microsatellite markers and alternations of the K-ras, p53 and mdm-2 genes in human ICC tissues. Overexpression of mdm-2 oncoprotein was also immunohistochemically studied. RESULTS: Of all 65 cases examined, K-ras gene mutation was found in three cases (4.6%) at codon 12. Analysis of p53 alterations was performed in 28 cases including 22 frozen samples and mutations were found in three cases (10.7%). Overexpression of mdm-2 protein was observed in 25 (41.7%) out of 60 cases analyzed. In 22 frozen samples, seven (31.8%) cases showed mdm-2 amplification and four (18.2%) cases revealed MSI-positive phenotype. Among the cases analyzed, all the tumors with mdm-2 amplification/overexpression harbored the wild-type p53 gene and all the microsatellite instability-positive cases were from mass-forming (MF) + periductal-infiltrating (PI) subtype. CONCLUSIONS: These results suggest that mdm-2 plays a role, which might be partially through inhibiting p53 activity, in cholangiocarcinogenesis and that M

Adult↗

Acute cholecystitis caused by a cholesterol polyp.

A 39-year-old man hospitalized with upper abdominal pain had been found to have a 3mm polyp in the body of the gallbladder 3 years previously. Laboratory tests on admission showed mild liver dysfunction. Ultrasonography depicted a dilated gallbladder with increased wall thickness; the polyp could no longer be seen. Computed tomography with drip infusion cholangiography again showed a dilated gallbladder, and also stenosis of the distal cystic duct. The resected specimen obtained by laparoscopic cholecystectomy showed disappearance of the polyp from the body of the gallbladder. A cholesterol stone was incarcerated in the cystic duct, representing an impacted detached cholesterol polyp causing acute cholecystitis. Spontaneous detachment of a cholesterol polyp from the gallbladder mucosa, then, can result in acute cholecystitis.

Acute Disease↗

Spontaneous disappearance of a hepatic cyst.

The spontaneous disappearance of a hepatic cyst is described. A 62-year-old woman presented with symptoms of general fatigue in August 1992. Her past medical history was significant for chronic hepatitis, which was diagnosed in 1990 but not treated. Initial laboratory tests revealed mild liver dysfunction with a positive serologic test for hepatitis C. In August 1992, ultrasonography and computed tomography disclosed a cystic lesion along the middle hepatic vein in the right anterior segment of the liver, which was 40 mm in diameter. Repeat radiologic studies in June 1994 demonstrated that the size of the cyst was unchanged. In May 1995, the cyst was only 25 mm in diameter, and it continued to decrease in size thereafter, to 10 mm in September 1995 and 7 mm in September 1996. No hepatic cyst was visualized in December 1996, though the region in which the cyst existed was hyperechoic. Laboratory data were essentially unchanged from August 1992 to December 1996. Clinically the patient remained asymptomatic.

Cysts↗

New methods of control against postoperative methicillin-resistant Staphylococcus aureus infection.

The incidence of postoperative infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in Japan has been increasing dramatically. In March 1990, we assigned special doctors in infection control (infection control doctor, ICD), and defined comprehensive controls against MRSA infection. A total of 3536 cases of digestive tract surgery performed at our department were studied during the period between September 1987 and August 1997. We changed the use of antibiotics to prevent postoperative infection. Cefazolin (CEZ) was employed for surgery of the upper digestive tract, including esophagus, stomach, duodenum, and gallbladder. Cefotiam (CTM) was employed for surgery of the lower digestive tract, liver, and pancreas. In esophageal resection, the tracheal tube was extracted during the early postoperative period, and for cervical esophagogastroanastomosis, the autosuture was changed to layer-to-layer anastomosis. We have achieved successful control of postoperative MRSA infection, the incidence having decreased to 0.3% (9/2703). In conclusion, our methods of control against postoperative MRSA infection implies that comprehensive measures of prevention, including the reviewed specification and usage of antibiotics and operation management, have been well implemented. This value is the lowest and the first of any domestic hospital or institute in Japan, suggesting a continued and significant decrease.

Cephalosporins↗

Thujaplicin-copper chelates inhibit replication of human influenza viruses.

The effects of alpha-, beta- and gamma-thujaplicins and six of their metal chelates on human influenza virus-induced apoptosis in Madin-Darby canine kidney (MDCK) cells were examined by DNA fragmentation and flow cytometry. Among the compounds tested, thujaplicin copper chelates inhibited apoptosis induced in the infected MDCK cells with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2), A/Aichi/2/68(H3N2) and B/Lee/40 viruses, at concentrations of more than 5 microM. These results indicate that the copper chelates inhibit influenza virus-induced apoptosis and that the inhibitory effects may be independent of influenza virus subtype or types. Furthermore, the copper chelates also inhibited the release of the viruses from the infected MDCK cells during apoptosis. The anti-apoptotic effects of the copper chelates may occur 2 4 h postinfection, suggesting that the copper chelates affect MDCK cells directly in the early stage of influenza virus-induced apoptosis. In this study, we demonstrated that thujaplicin-copper chelates inhibit influenza virus-induced apoptosis of MDCK cells and also inhibit virus replication and release from the infected cells.

Animals↗

Inhibitory effect of beta-thujaplicin on ultraviolet B-induced apoptosis in mouse keratinocytes.

Sunburn cells are thought to represent ultraviolet B-induced apoptotic keratinocytes. It has been demonstrated that enzymatic and nonenzymatic antioxidants effectively suppress sunburn cell formation, indicating that reactive oxygen species may play a role in the progression of ultraviolet B-induced apoptosis. Metallothionein, a cytosol protein, has antioxidant activity, and overexpression of metallothionein has been reported to reduce the number of sunburn cells in mouse skin. We have also demonstrated that overexpression of metallothionein inhibits ultraviolet B-induced DNA ladder formation in mouse keratinocytes. These findings support the hypothesis that cellular metallothionein may play an important role in the inhibition of ultraviolet B-induced apoptosis in keratinocytes through its antioxidant activity. In the present study, we investigated the effects of beta-thujaplicin, an extract from the woods of Thuja plicata D. Don. and Chamaecyparis obtuse, Sieb. et Zucc., on ultraviolet B-induced apoptosis in keratinocytes and on metallothionein induction. Topical application of beta-thujaplicin decreased the number of ultraviolet B-mediated sunburn cells and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling-positive cells in mouse ear skin. Incubation with beta-thujaplicin suppressed ultraviolet B-induced DNA ladder formation in cultured mouse keratinocytes. Histochemical analysis showed that topical application of beta-thujaplicin induced metallothionein protein in mouse skin. Northern analysis and western blotting revealed significant induction of metallothionein mRNA and metallothionein protein, respectively, in beta-thujaplicin-treated cultured mouse keratinocytes. These findings indicate that beta-thujaplicin inhibits ultraviolet B-induced apoptosis in keratinocytes and strongly suggest that the inhibitory mechanism is due to the antioxidant activity of metallothionein induced by the agent.

Animals↗

Beta-thujaplicin zinc chelate induces apoptosis in mouse high metastatic melanoma B16BL6 cells.

The cytotoxic effects of beta-thujaplicin and five kinds of metal chelates were examined on mouse melanoma B16BL6 cells by cell viability and lactate dehydrogenase (LDH) release assay. Beta-thujaplicin-zinc chelate and beta-thujaplicin-copper chelate had higher cytotoxic effects than beta-thujaplicin, and the 50% effective doses (ED50) of these metal chelates were 12.5 and 25 microM, respectively. In addition, the zinc chelate induced DNA ladder formation in B16BL6 cells, as shown by the DNA fragmentation assay, suggesting that cell death induced by the zinc chelate is apoptosis. The zinc chelate also had a cytotoxic effect and induced DNA fragmentation on other tumor cell lines: HeLa, Meth A, and B16F1 cells, but not on normal human diploid fibroblasts FS-4. These results suggest that beta-thujaplicin-zinc chelate induces apoptotic cell death in various tumor cell lines and is a potent antitumor agent for tumor cells including malignant melanomas.

Animals↗