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Biomedical subjects

Atsushi Kato

Publications and source records attributed to Atsushi Kato.

At least 37 records · Page 2Linked to original sources
PubMed2006

[Successful treatment for intractable ascites with uterine cancer using double Denver peritoneovenous shunt system].

A 59-year-old woman, who underwent uterectomy for uterine cancer in February 2000, was diagnosed having carcinomatous peritonitis with intractable ascites due to recurrent uterine cancer in November 2004. We conducted a peritoneovenous shunting at the right side of the abdominal cavity using the Denver peritoneovenous shunt system. A significant reduction in body weight and abdominal girth was seen during the follow up period. After 2 months, the intractable ascites was aggrayating. Because of the partition of the abdominal cavity by the greater omentum, the intractable ascites was dominant in the left side of the abdominal cavity compared with the right side. So we tried additional moreperitoneovenous shunting at the left side of the abdominal cavity using the Denver peritoneovenous shunt system. Finally, ascites and body weight were decreased. She was discharged from our hospital with a good quality of life. Double peritoneovenous shunt (Denver peritoneovenous shunt system) is a useful palliative treatment for intractable such as this case. Further experience and discussion are necessary to indicate this procedure.

Ascites↗
PubMed2006

[A patient with bile duct cancer who showed rapid obstruction after insertion of a non covered stent, but in this case obtained a stent opening and better QOL after reinsertion of a covered stent].

A 73-year-old man is presented with jaundice. Dynamic CT showed a papillary mass in the common bile duct. Percutaneous transhepatic cholangiography revealed a filling defect in the middle common bile duct. Poorly differentiated adenocarcinoma was demonstrated from a papillary mass in the common bile duct by biopsy specimens obtained under p. ercutaneous transhepatic cholangioscopy. Based on these findings, upper to middle bile duct cancer was diagnosed. An unresectable tumor was defined by involving the main portal vein and common hepatic artery at surgical exploration. A non-covered expandable metallic stent was placed 8 days after the operation. However, since contrast radiography showed tumor protrusion in the stent next day after the insertion, a covered stent was placed. Stent obstruction did not occur, and the patient was discharged from the hospital with a good quality of life. A covered stent can be more potentially and clinically effective than a non-covered stent especially for a papillary tumor in the bile duct.

Adenocarcinoma↗
PubMed2005

Vascular endothelial growth factor and angiopoietins regulate sinusoidal regeneration and remodeling after partial hepatectomy in rats.

AIM: To study the regulatory mechanisms of sinusoidal regeneration after partial hepatectomy. METHODS: We investigated the expression of angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in regenerating liver tissue by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler (Roche Diagnostics) and also immunohistochemical staining after 70% hepatectomy in rats. In the next step, we isolated liver cells (hepatocytes, sinusoidal endothelial cell (SEC), Kupffer cell, and hepatic stellate cells (HSC)) from regenerating liver tissue by in situ collagenase perfusion and counterflow elutriation, to determine potential cellular sources of these angiogenic factors after hepatectomy. Proliferation and apoptosis of SECs were also evaluated by proliferating cell nuclear antigen (PCNA) staining and the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay, respectively. RESULTS: VEGF mRNA expression increased with a peak at 72 h after hepatectomy, decreasing thereafter. The expression of Ang-1 mRNA was present at detectable levels before hepatectomy and increased slowly with a peak at 96 h. Meanwhile, Ang-2 mRNA was hardly detected before hepatectomy, but was remarkably induced at 120 and 144 h. In isolated cells, VEGF mRNA expression was found mainly in the hepatocyte fraction. Meanwhile, mRNA for Ang-1 and Ang-2 was found in the SEC and HSC fractions, but was more prominent in the latter. The PCNA labeling index of SECs increased slowly, reaching a peak at 72 h, whereas apoptotic SECs were detected between 120 h and 144 h. CONCLUSION: Ang-Tie system, together with VEGF, plays a critical role in regulating balance between SEC proliferation and apoptosis during sinusoidal regeneration after hepatectomy. However, the VEGF system plays a more important role in the early phase of sinusoidal regeneration than angiopoietin/Tie system.

Angiopoietin-1↗
PubMed2005

Id1 gene transfer confers angiogenic property on fully differentiated endothelial cells and contributes to therapeutic angiogenesis.

BACKGROUND: Transplantation of endothelial progenitor cells has been proposed as a potential strategy for therapeutic revascularization. However, the limited endogenous cell pool and the related technical difficulties constitute clinically important disadvantages to autologous transplantation. In this study we investigated whether fully differentiated endothelial cells (ECs) modified with gene transfer of Id1, a helix-loop-helix transcription factor involved in angiogenesis, have the potential to contribute to therapeutic angiogenesis. METHODS AND RESULTS: The Id1 gene was transferred into human umbilical vein ECs (HUVECs) via a Sendai virus vector. Id1 stimulated migration, proliferation, and capillary-like tube/cord formation of HUVECs. In addition, Id1 reduced serum deprivation-induced HUVEC apoptosis, as shown by FACS analysis with annexin V and TUNEL staining. Transplantation of Id1-overexpressing HUVECs accelerated recovery of blood flow as evaluated by laser-Doppler perfusion imaging, increased capillary density, and improved the rate of limb salvage compared with the transplantation of control HUVECs. Histochemical analysis revealed that the regenerated vascular networks of limbs transplanted with Id1-overexpressing HUVECs contained numerous HUVECs, some of which were in a proliferative state. Untransfected HUVECs were also incorporated with Id1-transfected HUVECs, suggesting the noncell autonomous effect of Id1. Finally, angiopoietin-1 was upregulated in Id1-overexpressing HUVECs and functionally contributed to the in vitro angiogenic effect of Id1. CONCLUSIONS: Id1 gene transfer conferred HUVECs with an angiogenic property, contributing to neovascularization after transplantation into ischemic lesions. Transplantation of Id1-overexpressing mature ECs may serve as a novel and useful strategy for therapeutic angiogenesis.

3' Untranslated Regions↗
PubMed2005

Renal function is well maintained after use of left renal vein graft for vascular reconstruction in hepatobiliary-pancreatic surgery.

BACKGROUND: Advanced hepatobiliary-pancreatic malignancy occasionally involves major vasculatures, such as the portal vein or the inferior vena cava, and complete removal of the tumor is required for longterm survival. We used a left renal vein graft to reconstruct resected vessels in some patients. In this study, we evaluated early and late renal complications of this procedure. STUDY DESIGN: We identified 14 patients undergoing vascular reconstruction with use of a left renal vein graft in hepatobiliary-pancreatic surgery. Renal function and graft patency were assessed by observing serum creatinine levels and radiologic findings during perioperative and followup periods. RESULTS: Of these 14 patients, 7 were men and 7 were women. Diseases included hilar cholangiocarcinoma in two, gallbladder carcinoma in two, intrahepatic cholangiocarcinoma in one, pancreas carcinoma in five, hepatic metastasis in three, and mass-forming pancreatitis in one. No significant postoperative renal dysfunction was recognized, and the mean value of the maximal serum creatinine was 1.0 mg/dL during the perioperative period. Renal scintigraphy was performed in six patients postoperatively, and there was no significant left renal dysfunction. Mean followup time was 18 months after operation, and no severe renal dysfunction was found. Graft patency, which was assessed with enhanced abdominal CT, was well maintained after operation. CONCLUSIONS: The left renal vein could be safely obtained and used for vascular reconstruction in resection of hepatobiliary-pancreatic malignancy without adverse effects on early and longterm renal function.

Adult↗
PubMed2005

Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity.

The cellular protein retinoic acid-inducible gene I (RIG-I) senses intracellular viral infection and triggers a signal for innate antiviral responses including the production of type I IFN. RIG-I contains a domain that belongs to a DExD/H-box helicase family and exhibits an N-terminal caspase recruitment domain (CARD) homology. There are three genes encoding RIG-I-related proteins in human and mouse genomes. Melanoma differentiation associated gene 5 (MDA5), which consists of CARD and a helicase domain, functions as a positive regulator, similarly to RIG-I. Both proteins sense viral RNA with a helicase domain and transmit a signal downstream by CARD; thus, these proteins share overlapping functions. Another protein, LGP2, lacks the CARD homology and functions as a negative regulator by interfering with the recognition of viral RNA by RIG-I and MDA5. The nonstructural protein 3/4A protein of hepatitis C virus blocks the signaling by RIG-I and MDA5; however, the V protein of the Sendai virus selectively abrogates the MDA5 function. These results highlight ingenious mechanisms for initiating antiviral innate immune responses and the action of virus-encoded inhibitors.

Animals↗
PubMed2005

Biological properties of D- and L-1-deoxyazasugars.

L-Enantiomers of 1-deoxynojirimycin (DNJ), 1-deoxymannojirimycin (manno-DNJ), 1-deoxyallonojirimycin (allo-DNJ), 1-deoxyaltronojirimycin (altro-DNJ), 1-deoxygalactonojirimycin (galacto-DNJ), 1-deoxygulonojirimycin (gulo-DNJ), and 1-deoxyidonojirimycin (ido-DNJ) were prepared according to prior methods for the d-enantiomers. These enantiospecific syntheses established unambiguously the absolute configuration of naturally occurring DNJ, manno-DNJ, allo-DNJ, altro-DNJ, and gulo-DNJ. Although d-DNJ and d-galacto-DNJ are known to be powerful competitive inhibitors of alpha-glucosidase and alpha-galactosidase, respectively, with K(i) values in the nM range, l-DNJ and l-galacto-DNJ were noncompetitive inhibitors of alpha-glucosidase and alpha-galactosidase, respectively, with K(i) values in the muM range. However, the azasugar mimicking the structure of the terminal sugar moiety of the natural substrate is not always an inhibitor of the glycosidase responsible for the hydrolysis. d-manno-DNJ is known as a much better inhibitor of alpha-l-fucosidase than alpha-mannosidase, while l-allo-DNJ was a better inhibitor than d-manno-DNJ of alpha-mannosidase. l-galacto-DNJ can be regarded as the 6-hydroxylated derivative of deoxyfuconojirimycin (DFJ), which is a powerful inhibitor of alpha-l-fucosidase with a K(i) value in the nM range. However, this replacement of the methyl group in DFJ by a hydroxymethyl group reduced its affinity by about 50-fold. This suggests that there is a hydrophobic region in or around the active site of alpha-l-fucosidase. It has been found that inhibitors of human lysosomal glycosidases have therapeutic potential for the corresponding lysosomal storage diseases (Nat. Med. 1999, 5, 112; Proc. Natl. Acad. Sci. USA, 2002, 99, 15428). Inhibition of human lysosomal glycosidases by the 1-deoxyazasugars synthesized was investigated. d-galacto-DNJ is a potent inhibitor of lysosomal alpha-galactosidase (IC(50) = 90 nM) and is now being evaluated preclinically for its potential use in Fabry disease, while d-DNJ inhibiting alpha-glucosidase (IC(50) = 40 nM) potently does not appear to become a potential therapeutic agent because of additional inhibitory activity toward glycoprotein processing alpha-glucosidases. On the other hand, although l-allo-DNJ is a moderate inhibitor of alpha-mannosidase (IC(50) = 64 microM), it may become a key compound for the drug design of potential therapeutic agents for alpha-mannosidosis.

1-Deoxynojirimycin↗
PubMed2005

General synthesis and biological evaluation of alpha-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-alpha-C-glycosides).

A general synthesis of alpha-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-alpha-C-glycosides) by ring-opening reactions of an aziridine with various heteroatomic nucleophiles, including thiol, amine, alcohol, carboxylate and phosphate, is described. The nine-step reaction sequence proceeded in an overall yield of 14-28% from tri-O-benzyl-D-glucal. Biological evaluation of alpha-1-C-substituted derivatives of fagomine, of the 2-deoxy analog of alpha-homonojirimycin 19 and its 1,N-anhydro derivative 22 as glycosidase inhibitors is reported. The glycosyl phosphate mimetic 15k was found to display no inhibitory activity towards glycogen phosphorylase b and phosphoglucomutase.

1-Deoxynojirimycin↗
PubMed2005

Should the inferior vena cava be reconstructed after resection for malignant tumors?

BACKGROUND: Caval replacement after circumferential resection of the inferior vena cava remains controversial. The aim of the current study is to determine whether or not inferior vena cava replacement should be performed. METHODS: We reviewed 36 cases undergoing resection of the inferior vena cava concomitant with resection of malignant neoplasms. Our criteria for circumferential resection of the inferior vena cava were half or more of the circumference of the vessel wall invaded by tumor, a primary tumor of the caval wall, or massive intraluminal tumor thrombus suspected of adhering to the caval wall. We detailed 10 patients undergoing circumferential resection of the inferior vena cava. RESULTS: Most of patients who did not undergo replacement of the inferior vena cava showed no sign of swelling of the lower limbs, but one showed persistent leg edema with oliguria. This patient had poor development of collateral circulation and mild obstruction of the inferior vena cava before surgery. Two patients who underwent replacement of inferior vena cava had no venous sequelae, although they had poor development of collateral circulation before surgery. CONCLUSION: Caval replacement after circumferential resection of the inferior vena cava may be necessary in patients who have preoperative poor development of collateral circulation or who have oliguria or unstable hemodynamics intraoperatively.

Adult↗
PubMed2005

Temperature adaptation in Dictyostelium: role of Delta5 fatty acid desaturase.

Membrane fluidity is critical for proper membrane function and is regulated in part by the proportion of unsaturated fatty acids present in membrane lipids. The proportion of these lipids in turn varies with temperature and may contribute to temperature adaptation in poikilothermic organisms. The fundamental question posed in this study was whether the unsaturation of fatty acids contributes to the ability to adapt to temperature stress in Dictyostelium. First, fatty acid composition was analysed and it was observed that the relative proportions of dienoic acids changed with temperature. To investigate the role of dienoic fatty acids in temperature adaptation, null mutants were created in the two known Delta5 fatty acid desaturases (FadA and FadB) that are responsible for the production of dienoic fatty acids. The fadB null mutant showed no significant alteration in fatty acid composition or in phenotype. However, the disruption of fadA resulted in a large drop in dienoic fatty acid content from 51.2 to 4.1 % and a possibly compensatory increase in monoenoic fatty acids (40.9-92.4 %). No difference was detected in temperature adaptation with that of wild-type cells during the growth phase. However, surprisingly, mutant cells developed more efficiently than the wild-type at elevated temperatures. These results show that the fatty acid composition of Dictyostelium changes with temperature and suggest that the regulation of dienoic fatty acid synthesis is involved in the development of Dictyostelium at elevated temperatures, but not during the growth phase.

Adaptation, Physiological↗
PubMed2005

AIP1/Alix is a binding partner of Sendai virus C protein and facilitates virus budding.

The C protein, an accessory protein of Sendai virus (SeV), has anti-interferon capacity and suppresses viral RNA synthesis. In addition, it is thought that the C protein is involved in virus budding because of the low efficiency of release of progeny virions from C-knockout virus-infected cells and because of the requirement of the C protein for efficient release of virus-like particles. Here, we identified AIP1/Alix, a host protein involved in apoptosis and endosomal membrane trafficking, as an interacting partner of the C protein using a yeast two-hybrid system. The amino terminus of AIP1/Alix and the carboxyl terminus of the C protein are important for the interaction in mammalian cells. Mutant C proteins unable to bind AIP1/Alix failed to accelerate the release of virus-like particles from cells. Furthermore, overexpression of AIP1/Alix enhanced SeV budding from infected cells in a C-protein-dependent manner, while the release of nucleocapsid-free empty virions was also enhanced. Finally, AIP1/Alix depletion by small interfering RNA resulted in suppression of SeV budding. The results of this study suggest that AIP1/Alix plays a role in efficient SeV budding and that the SeV C protein facilitates virus budding through interaction with AIP1/Alix.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2005

Mumps virus V protein antagonizes interferon without the complete degradation of STAT1.

Mumps virus (MuV) has been shown to antagonize the antiviral effects of interferon (IFN) through proteasome-mediated complete degradation of STAT1 by using the viral V protein (T. Kubota et al., Biochem. Biophys. Res. Commun. 283:255-259, 2001). However, we found that MuV could inhibit IFN signaling and the generation of a subsequent antiviral state long before the complete degradation of cellular STAT1 in infected cells. In MuV-infected cells, nuclear translocation and phosphorylation of STAT1 and STAT2 tyrosine residue (Y) at 701 and 689, respectively, by IFN-beta were significantly inhibited but the phosphorylation of Jak1 and Tyk2 was not inhibited. The transiently expressed MuV V protein also inhibited IFN-beta-induced Y701-STAT1 and Y689-STAT2 phosphorylation, suggesting that the V protein could block IFN-beta-induced signal transduction without the aid of other viral components. Finally, a substitution of an alanine residue in place of a cysteine residue in the C-terminal V-unique region known to be required for STAT1 degradation and inhibition of anti-IFN signaling resulted in the loss of V protein function to inhibit the Y701-STAT1 and Y689-STAT2 phosphorylation.

Amino Acid Substitution↗
PubMed2005

Induction of apoptosis in human promyelocytic leukemia cell line HL-60 by C-benzylated dihydrochalcones, uvaretin, isouvaretin and diuvaretin.

Uvaretin, isouvaretin and diuvaretin, cytotoxic C-benzylated dihydrochalcones isolated from Uvaria acuminata, displayed growth inhibitory effects against human promyelocytic leukemia HL-60 cells. We examined the mechanism of the cytotoxicity. From the morphological study by staining with Hoechst 33258, the cells treated with C-benzylated dihydrochalcones exhibited significant chromosomal condensation and nuclear degradation. The cell cycle analysis showed the accumulation of cells in the G1 phase and the appearance of a sub-G1 peak. These results suggest apoptotic cell death. Further, from the detection of DNA fragmentation and the activation of caspase-3, the biological hallmarks of apoptosis, these C-benzylated dihydrochalcones appeared to induce apoptosis against HL-60 cells. The cytotoxicity of uvaretin and diuvaretin was stronger than that of isouvaretin, which suggest that the 5'-substitution of the 2-hydroxybenzyl group increased the cytotoxicity.

Apoptosis↗
PubMed2005

The growth profiles of three types of canine distemper virus on Vero cells expressing canine signaling lymphocyte activation molecule.

To know growth profiles of canine distemper virus (CDV) on Vero cells stably expressing canine signaling lymphocyte activation molecule (Vero-DogSLAMtag; Vero-DST cells), the propagation of three strains of CDV was tested in Vero-DST cells in comparison with parental Vero cells. Strain MD77 could grow well in both cell lines, but demonstrated no syncytium formation or indistinguishable rounding cytopathic effects (CPE) in Vero cells. Strains Onderstepoort and KDK-1 also grew well in Vero-DST cells with apparent syncytium CPE, while they grew less or no efficiently, respectively, in Vero cells. All three CDV strains demonstrated the peak titers, in Vero-DST cells before reaching to an extensive CPE and drastic decrease of titers at/after full CPE. Immunohistochemistry revealed that viral antigens of all CDV strains were found exclusively in the syncytia in Vero-DST cells, while in Vero cells, viral antigen was identified in their single cells for strain MD77 but none for other strains. Thus, every strain of CDV could grow well in Vero-DST cells and behaved differently against Vero cells. These results would be of practical value for workers of CDV because 1) In Vero-DST cells, by observation of distinct syncytium CPE, the highest titer or the best growth of virus could be identified; 2) In Vero cells, various CDV strains could be readily classified after propagation in Vero-DST cells.

Animals↗
PubMed2005

[Hilar cholangiocarcinoma].

Surgical resection has been reported to be only hope for cure for the patients with hilar cholangiocarcinoma. Therefore, first of all, radical surgical resection should be considered to be a therapeutic option for hilar cholangiocarcinoma as much as possible. In preoperative staging for hilar cholangiocarcinoma, various extensive patterns of cancer such as the involvements of bile duct, portal vein, hepatic artery and lymph node etc, should be evaluated in each patient. As most patients are associated with obstructive jaundice at presentation, liver function has to be evaluated by appropriate tests for deciding the suitable surgical procedure. When the future remnant liver volume is less than 40% or severe liver functional damage exists or greater surgical stress is expected, preoperative portal vein embolization might have to be selected. On the other hand, if hilar cholangiocarcinoma involves limited region of the hilar bile duct confluence, parenchyma preserving hepatectomy such as S1 resection and S1 + S4 resection should be selected for avoiding the occurrence of liver failure. Combined portal vein resection should be done for the case of the cancer involvement of the portal vein without hesitation to improve the prognosis. However, hepatic artery resection and reconstruction in the involved case should be carefully performed only in severely selected cases. By using several useful pre-operative and intra-operative therapeutic modalities, hilar cholangiocarcinoma should be surgically resected with curative intent and without increasing surgical morbidity and mortality rates.

Bile Duct Neoplasms↗