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Y Ogata

Publications and source records attributed to Y Ogata.

At least 19 recordsLinked to original sources
PubMed2003

Large-scale production and properties of human plasma-derived activated Factor VII concentrate.

BACKGROUND AND OBJECTIVES: An activated Factor VII (FVIIa) concentrate, prepared from human plasma on a large scale, has to date not been available for clinical use for haemophiliacs with antibodies against FVIII and FIX. In the present study, we attempted to establish a large-scale manufacturing process to obtain plasma-derived FVIIa concentrate with high recovery and safety, and to characterize its biochemical and biological properties. MATERIALS AND METHODS: FVII was purified from human cryoprecipitate-poor plasma, by a combination of anion exchange and immunoaffinity chromatography, using Ca2+-dependent anti-FVII monoclonal antibody. To activate FVII, a FVII preparation that was nanofiltered using a Bemberg Microporous Membrane-15 nm was partially converted to FVIIa by autoactivation on an anion-exchange resin. The residual FVII in the FVII and FVIIa mixture was completely activated by further incubating the mixture in the presence of Ca2+ for 18 h at 10 degrees C, without any additional activators. For preparation of the FVIIa concentrate, after dialysis of FVIIa against 20 mm citrate, pH 6.9, containing 13 mm glycine and 240 mm NaCl, the FVIIa preparation was supplemented with 2.5% human albumin (which was first pasteurized at 60 degrees C for 10 h) and lyophilized in vials. To inactivate viruses contaminating the FVIIa concentrate, the lyophilized product was further heated at 65 degrees C for 96 h in a water bath. RESULTS: Total recovery of FVII from 15 000 l of plasma was approximately 40%, and the FVII preparation was fully converted to FVIIa with trace amounts of degraded products (FVIIabeta and FVIIagamma). The specific activity of the FVIIa was approximately 40 U/ micro g. Furthermore, virus-spiking tests demonstrated that immunoaffinity chromatography, nanofiltration and dry-heating effectively removed and inactivated the spiked viruses in the FVIIa. These results indicated that the FVIIa concentrate had both high specific activity and safety. CONCLUSIONS: We established a large-scale manufacturing process of human plasma-derived FVIIa concentrate with a high yield, making it possible to provide sufficient FVIIa concentrate for use in haemophiliacs with inhibitory antibodies.

Blood Component Transfusion↗
PubMed2002

Successful bone marrow transplantation from an unrelated donor in a patient with adult T cell leukemia.

We report a 51-year-old male with adult T cell leukemia (ATL) who received a BMT from an HLA-identical unrelated donor. The ATL proved refractory to chemotherapy, and he underwent BMT conditioned with CY/TBI. Complications of encephalitis of unknown origin were successfully treated with steroid therapy and the patient has been in CR for 16 months after BMT. Human T cell leukemia virus type 1 proviral DNA loads were reduced to undetectable levels in PBMC sampled 12 months after BMT. This encouraging result suggests that BMT from an unrelated donor should be considered for ATL even if the disease is refractory to chemotherapy.

Bone Marrow Transplantation↗
PubMed2001

Phagocytosis in vitro of polyethylene glycol-modified liposome-encapsulated hemoglobin by human peripheral blood monocytes plus macrophages through scavenger receptors.

Liposome-encapsulated hemoglobin (LEH), a candidate for red blood cell substitute, is cleared from circulation primarily by the phagocytic system, most likely after opsonization of the vesicles by immunoproteins, particularly complement components. Although modification of LEH by polyethylene glycol (PEG) derivatives prolongs its half-life by blocking the opsonization, the half-life is still short as compared with that of red blood cell components. Therefore, this study was performed to elucidate the opsonin-independent mechanisms that regulate phagocytosis of Neo Red Cell (NRC), a PEG-modified LEH, in culture. PKH67 was used as a fluorescence marker, allowing the quantitation of the phagocytosis of NRC by peripheral blood monocytes plus macrophages. The phagocytosis of PKH67-labeled NRC was inhibited by the addition of an excess of unlabeled NRC, indicating that the phagocytosis of PKH67-labeled NRC is specific to NRC, but not to PKH67. The phagocytosis of NRC was blocked about 70% by anti-CD14, 60% by anti-CD36 and 30% by anti-CD51/61 (vitronectin receptor, alpha(v)beta3). These results provided evidence of an opsonin-independent pathway for the phagocytosis of PEG-modified LEH.

Antigens, CD↗
PubMed2001

Liposome-encapsulated superoxide dismutase suppresses liposome-mediated augmentation of TNF-alpha production from peripheral blood leucocytes.

Liposome-encapsulated hemoglobin (LEH), a candidate for a red cell substitute, has been reported to be cleared from circulation primarily by the phagocytic system and modulate the production of inflammatory cytokines, such as TNF-alpha and IL-6, both in vivo and in vitro. In this study, we investigated the effects of liposome vesicles on the LPS-induced TNF-alpha production using a whole blood culture system. We also studied the effects of superoxide dismutase (SOD) encapsulated in liposome on the cytokine production. The pre-treatment of whole blood with liposome vesicles potentiated the LPS-induced TNF-alpha production. The encapsulation of SOD in the liposome vesicles suppressed the liposome-mediated augmentation of TNF-alpha production in a dose-dependent manner. These results suggest that encapsulation of SOD in LEH decreases the production of inflammatory cytokines from the phagocytic system which may be caused or augmented by LEH infusion in vivo.

Drug Carriers↗
PubMed2001

Mechanism of the SDS-resistant synaptotagmin clustering mediated by the cysteine cluster at the interface between the transmembrane and spacer domains.

Synaptotagmin I (Syt I), a proposed major Ca(2+) sensor in the central nervous system, has been hypothesized as functioning in an oligomerized state during neurotransmitter release. We previously showed that Syts I, II, VII, and VIII form a stable SDS-resistant, beta-mercaptoethanol-insensitive, and Ca(2+)-independent oligomer surrounding the transmembrane domain (Fukuda, M., and Mikoshiba, K. (2000) J. Biol. Chem. 275, 28180-28185), but little is known about the molecular mechanism of the Ca(2+)-independent oligomerization by the synaptotagmin family. In this study, we analyzed the Ca(2+)-independent oligomerization properties of Syt I and found that it shows two distinct forms of self-oligomerization activity: stable SDS-resistant self-oligomerization activity and relatively unstable SDS-sensitive self-oligomerization activity. The former was found to be mediated by a post-translationally modified (i.e. fatty-acylated) cysteine (Cys) cluster (Cys-74, Cys-75, Cys-77, Cys-79, and Cys-82) at the interface between the transmembrane and spacer domains of Syt I. We also show that the number of Cys residues at the interface between the transmembrane and spacer domains determines the SDS- resistant oligomerizing capacity of each synaptotagmin isoform: Syt II, which contains seven Cys residues, showed the strongest SDS-resistant oligomerizing activity in the synaptotagmin family, whereas Syt XII, which has no Cys residues, did not form any SDS-resistant oligomers. The latter SDS-sensitive self-oligomerization of Syt I is mediated by the spacer domain, because deletion of the whole spacer domain, including the Cys cluster, abolished it, whereas a Syt I(CA) mutant carrying Cys to Ala substitutions still exhibited self-oligomerization. Based on these results, we propose that the oligomerization of the synaptotagmin family is regulated by two distinct mechanisms: the stable SDS-resistant oligomerization is mediated by the modified Cys cluster, whereas the relatively unstable (SDS-sensitive) oligomerization is mediated by the environment of the spacer domain.

Amino Acid Sequence↗
PubMed2001

Expression of vascular endothelial growth factor and its receptor KDR (kinase domain-containing receptor)/Flk-1 (fetal liver kinase-1) as prognostic factors in human colorectal cancer.

BACKGROUND: To clarify the clinical significance of the expression of vascular endothelial growth factor (VEGF) and its receptor, kinase domain-containing receptor (KDR) in colorectal cancer, we evaluated the relationship between the expression of VEGF and KDR, and the microvessel counts and clinicopathological factors in colorectal cancer. METHODS: A total of 259 specimens from sequential colorectal cancer patients who had undergone surgery were examined by the avidin-biotin peroxidase complex method, using anti-human VEGF, anti-human KDR, and anti-human von Willebrand factor antibodies. RESULTS: The incidence of VEGF expression in the tumor cells of the patients with liver metastasis was significantly higher than that in the tumor cells of the patients without liver metastasis (67% vs 44%). The microvessel count at the tumor invasive edge in the patients whose tumor cells were positive for VEGF was significantly higher than that in the patients whose tumor cells were negative for VEGF (33.0 +/- 7.8 vs 28.0 +/- 7.9); the significant difference in microvessel counts was greater when there was a combination of VEGF and KDR expression. The overall survival rate of patients positive for VEGF was significantly (P = 0.0276) lower than that of those who were negative for VEGF. Although there was no significant difference (P = 0.0743) in the survival rates after potentially curative resection according to VEGF expression, the survival rate of the patients positive for both VEGF in tumor cells and KDR in endothelial cells was significantly (P = 0.0026) lower than that in the patients who were negative for VEGF and/or KDR. In addition, multivariate analysis revealed that the expression of both VEGF and KDR was an independent prognostic factor even after potentially curative resection. CONCLUSION: VEGF may be implicated in the definition of the malignant phenotype of colorectal cancer via tumor angiogenesis. VEGF and its receptor KDR expression in tumorous tissues could be useful prognostic factors in colorectal cancer.

Adenocarcinoma↗
PubMed2001

Inhibition of liver metastasis from orthotopically implanted colon cancer in nude mice by transfection of the TIMP-1 gene into KM12SM cells.

To determine whether the tissue inhibitor of metalloproteinases 1 (TIMP-1) can modulate in vivo tumor growth and metastasis, we transfected TIMP-1 cDNA into KM12SM human colon carcinoma cells and determined the implanted tumor volume and incidence of liver metastasis in orthotopically implanted colon cancer in nude mice. We also treated the implanted tumors with repeated intraperitoneal injections of recombinant human TIMP-1 (rTIMP-1), and compared the inhibitory efficacy on liver metastasis with that achieved by the TIMP-1 transfectants. The TIMP-1 transfectants had a significantly greater inhibitory effect, in association with TIMP-1 expression, on the growth of the primary tumor and on liver metastasis as compared with the controls. However, the intraperitoneal administration of rTIMP-1 did not decrease the rate of liver metastasis. In situ hybridization demonstrated that TIMP-1 mRNA in the cecal tumors implanted with the highly produced KM12SMT-2 cells with TIMP-1 was mainly expressed by the tumor cells. These results suggest that the increased expression of TIMP-1 in KM12SM cells was responsible for their decreased metastatic potential, and that the endogenous increase in TIMP-1 production by the tumor cells might be more effective for counteracting the matrix metalloproteinases (MMPs) in tumor tissue and for inhibiting liver metastasis from colon cancer than the exogenous administration of TIMPs.

Animals↗
PubMed2001

Cronkhite-Canada syndrome associated with advanced rectal cancer treated by a subtotal colectomy: report of a case.

A 41-year-old man with Cronkhite-Canada syndrome presented with multiple juvenile polyps with hyperplastic and adenomatous changes throughout his stomach and entire colorectum. Dysgeusia was recognized and the degree of hypoproteinemia was remarkable. A barium enema study and colonofiberscopy also revealed an advanced cancer in the rectum. Chronic hepatitis B and membranous glomerulonephritis were also present. It was difficult to design a conservative protocol using steroids for the treatment of protein-loosing enteropathy because the patient was a hepatitis B virus carrier. As a result, a subtotal colectomy while preserving the cecum with cecorectal anastomosis was performed. Pathologically, the ulcerated rectal tumor was a moderately differentiated adenocarcinoma with invasion into the muscularis propria. Most polyps showed cystically dilated glands without dysplasia or edematous stroma with inflammatory cell infiltration. A few polyps were juvenile-type polyps with adenoma components. Although no remarkable improvement was observed in the hypoproteinemia postoperatively, an alpha1-antitrypsin clearance test showed a significant decrease in protein loss from the gastrointestinal tract, which was only about one third of the loss seen preoperatively. These findings lead us to conclude that when improvement using conservative treatment can be neither obtained nor is expected, then the use of surgery should be considered when treating patients with Cronkhite-Canada syndrome.

Adenocarcinoma↗
PubMed2001

Physiological function of bromoperoxidase in the red marine alga, Corallina pilulifera: production of bromoform as an allelochemical and the simultaneous elimination of hydrogen peroxide.

The physiological function of vanadium-bromoperoxidase (BPO) in the marine red alga, Corallina pilulifera, has been characterized from the viewpoint of allelochemical formation. The algae emit bromoform (CHBr3) depending on the enzyme activity level in vivo (Itoh, N., Shinya, M., 1994. Seasonal evolution of bromomethanes from coralline algae and its effect on atmospheric ozone. Marine Chemistry 45, 95-103). We demonstrated that bromoform produced by C. pilulifera played an important role in eliminating epiphytic organisms, especially microalgae on the surface. Such data suggest a strong relationship between the coralline algae and the coralline flat (deforested area in the marine environment: called isoyake in Japanese). Lithophyllum yessoense, the main inhabitant of coralline flats in Japan, produced a lower level of CHBr3 than C. pilulifera, and showed BPO activity. On the other hand, the seasonal change of BPO activity in C. pilulifera in vivo was in proportion to superoxide dismutase (SOD) activity and in inverse proportion to catalase activity. The phenomenon implies that BPO could be a potential substitute for catalase, because the enzyme catalyzes an efficient Br(-)-dependent catalase reaction.

Benzopyrans↗
PubMed2001

Feasibility of in vivo thyroid 131I monitoring with an imaging plate.

A new in vivo thyroid 131I monitoring method was devised by using an imaging plate (IP). A thyroid image obtained with a realistic neck-thyroid phantom showed a unique shape characteristic of the thyroid gland. A 131I thyroid imaging allows visual confirmation of thyroid accumulation of 131I. The detection limit of the IP system of 290 Bq was about 1/100 of the screening level of 30 kBq in cases of public emergencies. The IP system is applicable for thyroid 131I monitoring.

Humans↗
PubMed2001

Tumor necrosis factor-alpha cooperates with receptor activator of nuclear factor kappaB ligand in generation of osteoclasts in stromal cell-depleted rat bone marrow cell culture.

A member of the tumor necrosis factor (TNF) family, receptor activator of nuclear factor kappaB ligand (RANKL; also known as ODF, OPGL, and TRANCE), plays critical roles in osteoclast differentiation and activation in the presence of macrophage colony-stimulating factor (M-CSF). Recently, TNF-alpha has also been shown to induce the formation of multinucleated osteoclast-like cells (MNCs) in the presence of M-CSF from mouse macrophages. We demonstrated that mononuclear preosteoclast-like cells (POCs) were formed in the presence of conditioned medium of osteoblastic cells in a rat bone marrow culture depleted of stromal cells. Using this culture system, in this study we examined whether TNF-alpha affects differentiation into POCs from hematopoietic progenitor cells. Human TNF-alpha (hTNF-alpha) markedly stimulated the formation of POCs. Moreover, a concentration as low as 0.005 ng/mL of hTNF-alpha increased the level of mRNA for calcitonin receptor (CTR) and cathepsin-K of POCs. The POCs induced by hTNF-alpha formed MNCs, which showed dentine-resorbing activity after coculture with primary osteoblasts. Stimulation was observed after 24 h of treatment with hTNF-alpha only on day 1 or day 2 of the culture. After 24 h of hTNF-alpha treatment, expression of the receptor activator of nuclear factor kappaB (RANK) mRNA was markedly increased. The addition of soluble RANKL (sRANKL) to the preformed POCs efficiently induced MNCs. Interestingly, treatment of bone marrow cells with hTNF-alpha and sRANKL synergistically augmented the formation of MNCs. This formation was abolished by the addition of human osteoprotegerin (hOPG). These results suggest that cooperation of TNF-alpha and RANKL is important for osteoclastogenesis.

Animals↗
PubMed2001

Bradykinin induces a rapid cyclooxygenase-2 mRNA expression via Ca2+ mobilization in human gingival fibroblasts primed with interleukin-1 beta.

We have previously demonstrated that bradykinin potentiates prostaglandin E(2)release in human gingival fibroblasts pretreated with interleukin-1 beta (priming). In this study, we demonstrate a potentiating effect of bradykinin on cyclooxygenase-2 mRNA expression in the interleukin-1 beta-primed fibroblasts. Interleukin-1 beta (200 pg/ml) induced cyclooxygenase-2 mRNA expression, but not bradykinin (1 microM). However, bradykinin rapidly and markedly increased the cyclooxygenase-2 mRNA expression in the fibroblasts primed with interleukin-1 beta. In the primed fibroblasts, ionomycin and thapsigargin mimicked the potentiating effect of bradykinin on the cyclooxygenase-2 mRNA expression. Dexamethasone and actinomycin D completely suppressed not only the interleukin-1 beta-induced cyclooxygenase-2 mRNA expression, but also the bradykinin-induced cyclooxygenase-2 mRNA expression in the interleukin-1 beta-primed fibroblasts, although cycloheximide did not inhibit the effects of interleukin-1 beta and bradykinin. These results suggest that bradykinin-induced prostaglandin E2 synthesis is regulated at the level of the transcription of cyclooxygenase-2 mRNA via Ca2+ mobilization in the interleukin-1 beta-primed human gingival fibroblasts.

Bradykinin↗
PubMed2001

Circular stapling procedure for mucosal prolapse of the rectum associated with outlet obstruction.

The aim of this study was designed to investigate the outcome from using the new circular stapling device in the surgical treatment for mucosal prolapse of the rectum associated with outlet obstruction. The treatment consisted of resection of the mucosal prolapse through a transverse incision and resecting a suitable part of the mucosa between the rectum and the anal canal, using an HCS33 circular stapler. Eleven patients successfully underwent this operation without morbidity or mortality, and were assessed clinically and by rectoanal manometry and defecography pre- and post-operation. The mean operating time was 39 (range 22-49) min. The postoperative proctalgia and complications were mild, and the patients were discharged at 4 days after the operation. The pre-operative constipation was improved, and the patient's satisfaction was increased at one month after operation in comparison with the preoperative level. Rectoanal function test at 6 months after the operation demonstrated normalization of the maximum resting and squeezing pressures of the anal canal and rectal compliance to the normal levels. No patient has had recurrence of symptoms during the follow-up period. Our data suggest that this procedure may be a useful surgical treatment, as it causes little postoperative complication and enables early discharge of the patients. However, long-term outcomes of recurrence, continence, and constipation need to be evaluated in a more extended follow-up.

Female↗
PubMed2001

Imbalance between matrix metalloproteinase 9 and tissue inhibitor of metalloproteinases 1 expression by tumor cells implicated in liver metastasis from colorectal carcinoma.

We have evaluated the degree of MMP-9 and TIMP-1 messenger RNA (mRNA) expressions according to cell types in tumor tissues, and evaluated the implication of balance between the MMP-9 mRNA and the TIMP-1 mRNA expression in liver metastasis using orthotopic-implanted colon cancer in nude mouse, and also in 47 patients with colorectal cancer. The grade of MMP-9 or TIMP-1 mRNA expression was classified into 4 categories according to positive cell ratio. A higher grade of MMP-9 mRNA expression in tumor cells was correlated with liver metastasis in the experimental colon cancer, but was not statistically correlated in the clinical colorectal cancer. In contrast, the expression of TIMP-1 mRNA in the stromal cells of human colorectal cancer was correlated with liver metastasis. In both experimental and clinical colorectal cancer, a balance between the expression of MMP-9 mRNA and that of TIMP-1 mRNA was correlated with the occurrence of liver metastasis. The imbalance of MMP-9 dominance in tumor cells was implicated in liver metastasis. However, there was no significant relationship between the incidence of liver metastasis and the expression patterns of MMP-9 and TIMP-1 mRNA in the stromal cells. These results suggest that the balance between the expressions of MMP-9 and TIMP-1 in the tumor cells is more closely related to tumor biological behavior rather than the balance in the stromal cells.

Adult↗
PubMed2001

The effect of angiogenesis inhibitor TNP-470 against postoperative lung metastasis following removal of orthotopic transplanted human colon cancer: an experimental study.

We have investigated the antimetastatic effect of TNP-470 against postoperative lung metastasis following the removal of human colon cancer xenotransplanted into nude rat. The KM12SM human colon cells were injected into the cecal wall. At 5 weeks after the injection, the cecum was removed including the tumor. Then, TNP-470 was administered continuously by subcutaneous injection pump at a dosage of 30 mg/kg/week. The Control Group received no administration of TNP-470. Group A and Group B received administration of TNP-470 just after the cecal removal for 4 and 2 weeks, respectively. Group C received 2 weeks' administration of TNP-470 from week 3 after the removal. The survival rate of each group was calculated, and any lung metastasis was evaluated macro and microscopically. At 7 weeks after the removal, lung metastasis was detected in all rats of the Control Group, and in 4 of 8 rats in Group C. In Groups A and Group B, only one rat developed lung metastasis. The 30 week-survival rate in Group A and that in Group B was significantly higher than that in the Control Group or Group C. Moreover, the incidence of lung metastasis at the time of death or 30 weeks after the removal in Group A, and in Group B, was lower than that in Control Group or Group C. The angiogenesis inhibitor, TNP-470 showed an excellent antimetastatic effect against postoperative lung metastasis from transplanted human colon cancer.

Angiogenesis Inhibitors↗
PubMed2001

Total mesorectal excision, lateral lymphadenectomy and autonomic nerve preservation for lower rectal cancer: significance in the long-term follow-up study.

We clarify the significance of total mesorectal excision (TME), lateral lymphadenectomy (LLA), and of autonomic nerve preservation (ANP) compared to conventional surgery (CVS), for lower rectal cancer. All 458 patients curatively resected between 1962 and 1997 were retrospectively investigated. In Period I from 1962-1974, when CVS only was performed, in Period II from 1975-1984, TME or TME + LLA was performed, and in Period III from 1985-1997, TME + ANP, TME + ANP + LLA, or TME + LLA was performed. In Dukes A + B disease, there was no significant difference among the three periods, regardless of operation methods. In Dukes C disease, in Period I, CVS (42 patients: pts) had a local recurrence (LR) rate of 45.2% and 5-year disease-free survival (5YDFS) rate of 33.3%. In Period II, TME + LLA (82 pts) had a lower LR rate of 26.8% (p = 0.0628) and higher 5YDFS 51.0% (p < 0.05) vs CVS. In Period III, TME + ANP (12 pts) had LR 25.0% and 5YDFS 55.6%, TME + ANP + LLA (45 pts) had LR 13.3% (p < 0.005, vs CVS) and 5YDFS 56.1% (p < 0.01, vs CVS), and TME + LLA (18 pts) had LR 16.7% (p < 0.05, vs CVS) and 5YDFS 20.8%. Also, CVS had the lowest curability rate 64.8% and the highest mortality rate 7.2%. TME and/or LLA was significant for reducing LR and improving survival in patients with Dukes C lower rectal cancer, compared to CVS. ANP was beneficial with LLA. TME + ANP was suitable for Dukes A or B disease.

Autonomic Nervous System↗
PubMed2001

The usefulness of restorative laparoscopic-assisted total colectomy for ulcerative colitis.

The aim of this study was to evaluate the effectiveness of laparoscopic-assisted total colectomy with ileal J-pouch anal anastomosis in comparison with that of conventional open total colectomy in patients with ulcerative colitis. From 1990 until 1999, 11 patients underwent open total colectomy, while 21 patients had laparoscopic-assisted total colectomy. Patients characteristics, perioperative course, and recovery were compared. Differences between the groups were tested using Student's t-test for independent groups and chi-square tests when appropriate. Nasogastric tube could be removed after POD 1.1 vs. 4.8 (p < 0.05), the mean time to passage of stool was 1.7 (range, 1 to 3) vs. 5.4 (range, 3 to 7) days (p < 0.05), and in the laparoscopic group watery stool was soon made solid after POD 24.3 vs. 87.3 (p < 0.01). There were no significant differences in the mean operating time and mean estimated operating blood loss between two groups. Postoperative morbidity did not differ significantly between the patients treated conventionally (45.5%) and laparoscopically (33.3%). The findings of this study indicate that laparoscopic-assisted total colectomy improved cosmetic results and to be a safe and effective treatment for the elective surgery of ulcerative colitis.

Adult↗