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Tadao Manabe

Publications and source records attributed to Tadao Manabe.

At least 37 records · Page 2Linked to original sources
PubMed2005

Anaplastic carcinoma of the pancreas with squamous features: report of a case and immunohistochemical study.

BACKGROUND: Anaplastic carcinomas of the pancreas are rare aggressive tumors with survival measurable in weeks. Many terms have been applied used to describe these tumors, and anaplastic foci are identified in ductal adenocarcinomas and in ectopic pancreata, but are not the dominant pattern of growth. We herein present our experience with a case of anaplastic carcinoma of the pancreas with squamous features in order that allowed us to delineate the clinicopathologic and immunohistochemical features of this rare entity. CASE REPORT: According to imaging findings, the 77-year-old Japanese man was diagnosed as the malignant pancreatic tumor, and underwent a surgical resection. Histopathologically, anaplastic tumor cells showed focal ductal and squamous features infiltrated into pancreatic parenchyma, extrapancreatic fatty tissue, and stomach. The tumor cells showed strong reactivity for cytokeratin, alpha-SMA, vimentin, NSE, and S-100 protein. Although immunoreactivity against p53 was negative, strong positive immunostaining for proliferating cell nuclear antigen and interleukin-1 receptor type I (IL-1RI) was observed in a the majority of tumor cells, while the alpha6 integrin subunit was predominantly strong expressed in the adenocarcinomatous lesion. The patient's postoperative course was uneventful and he was treated with a chemotherapy consisting of gemcitabine. After discharging from the hospital, he had subsequently been observed as an outpatient and same chemotherapy was followed by weekly. However, the patient suffered from peritonitis carcinomatosa and re-increases of multiple liver metastases, and he died in the fourteenth month after surgery. CONCLUSIONS: Our immunohistochemical studies suggested that the prognosis of the case with anaplastic carcinoma presented here would be poor, due to the strong expression of integrins and IL-1RI.

Aged↗
PubMed2004

Nitric oxide formation and plasma L-arginine levels in pulmonary hypertensive rats.

The elevation of plasma L-arginine levels stimulates nitric oxide (NO) synthesis, but the underlying mechanisms are not yet understood. We examined the role of physiological changes in pulmonary arteries on endogenous NO production. Male Wistar rats were divided into following groups: (1) control rats receiving normal water orally, (2) ARG rats receiving L-arginine water orally, (3) MCT rats injected with monocrotaline (MCT) on day 0 and receiving normal water orally, and (4) MCT+ARG rats injected with MCT on day 0 and receiving L-arginine water orally. The rats were studied after 23 days of dietary intervention. In MCT+ARG rats, supplemental L-arginine exhibited a significant pulmonary vasodilatory effect, as shown by a decreased pulmonary arterial pressure (PAP) (P<0.001), decreased right ventricular hypertrophy (P<0.01), and improved endothelium-dependent relaxation (P<0.01). Also L-arginine inhibited the elevation of plasma endothelin-1 (P<0.01). Oral L-arginine administration increased plasma L-arginine levels about twofold, but in only MCT+ARG rats (i.e., not in ARG rats) did the urinary nitrate excretion significantly increase (P<0.05), which is an indicator of endogenous NO formation. Oral administration of L-arginine is effective against pulmonary vascular remodeling. The data also suggest that the initial elevation of PAP is important for the induction of endogenous NO synthesis.

Animals↗
PubMed2004

Expression of integrins in intraductal papillary-mucinous tumors of the pancreas as an indicator of malignancy.

INTRODUCTION AND AIMS: Intraductal papillary-mucinous tumors (IPMTs) of the pancreas are intraductal tumors with diffuse or segmental dilation of the pancreatic ducts and intraductal papillary growth with abundant mucous secretion. We examined clinicopathological features and immunohistochemical findings to investigate the malignancy of IPMTs. METHODOLOGY: Between April 1994 and December 2002, 23 patients with IPMT underwent pancreatic resections at Nagoya City University Hospital, Japan. We immunohistochemically analyzed the expression of p53 protein, proliferating cell nuclear antigen, alpha6-integrin subunit, alpha5beta1 integrin, and interleukin-1 receptor type I in tumor specimens from the 23 patients with IPMT. RESULTS: The tumors were classified as intraductal papillary adenoma (n = 16), intraductal papillary adenocarcinoma and moderate dysplasia (n = 7). At a median follow-up of 42.9 months, 2 patients had died of this disease. The actuarial 5-year disease-free survival rate was 80.7%. Expression of the alpha6-integrin subunit was significantly strong in adenocarcinoma and moderate dysplasia tissues of IPMTs (P = 0.038). CONCLUSIONS: Our current results indicate that alpha6-containing integrin expression can be a significant marker of malignancy in IPMTs. We emphasize that immunohistochemical investigation of resected specimens is indispensable in cases of IPMT, so that appropriate postoperative treatments for malignant IPMTs are initiated to improve prognosis.

Adenocarcinoma, Mucinous↗
PubMed2004

Enhanced angiogenesis due to inflammatory cytokines from pancreatic cancer cell lines and relation to metastatic potential.

OBJECTIVES: To investigate the mechanisms of metastasis formation in human pancreatic carcinoma, we examined the angiogenic capabilities of human pancreatic cancer cell lines with different metastatic potentials and the roles of inflammatory cytokines. METHODS: Interleukin (IL)-8 secretion by human pancreatic cancer cells stimulated with IL-1alpha or IL-1 receptor antagonist (IL-1ra) was measured by enzyme-linked immunosorbent assay (ELISA). We then examined how cancer cells with different metastatic potentials influenced the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction method (MTT assay) and an angiogenesis assay, respectively. We also examined the role of inflammatory cytokines in relation to tumor metastatic potential and angiogenesis. RESULTS: IL-8 secretion levels by pancreatic cancer cells were regulated by IL-1alpha and correlated with metastatic potential. Both HUVEC proliferation and tube formation were strongly enhanced by coculture with metastatic pancreatic cancer cells and were enhanced to a similar extent by culture in the presence of IL-1alpha and IL-8. In contrast, blockade of IL-1alpha or IL-8 inhibited HUVEC proliferation and angiogenesis. CONCLUSIONS: The inflammatory cytokines IL-1alpha and IL-8 may have an important role in metastasis via vascular endothelial cell proliferation and angiogenesis.

Cell Division↗
PubMed2004

Glial cell line-derived neurotrophic factor enhances nuclear factor-kappaB activity and invasive potential in human pancreatic cancer cells.

OBJECTIVES: The invasive potential is increased by glial cell line-derived neurotrophic factor (GDNF) in human pancreatic cancer cell lines. We researched whether the signaling pathway activated by GDNF correlates with the nuclear factor-kappaB (NF-kappaB) in human pancreatic cancer cell lines and whether the inhibition of NF-kappaB activity is associated with suppression of invasive potential. METHODS: Proliferation of human pancreatic cancer cell lines (BxPC-3 and MIA PaCa-2) was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays (MTT assay). NF-kappaB activity was examined by dual luciferase assay and electrophoretic mobility shift assay. In addition, to investigate the invasive potential, an in vitro invasion assay was performed. RESULTS: Proliferation of both cell lines was decreased by a proteasome inhibitor, MG132, in a dose-dependent manner, but proliferation of control and IkappaBalphaM vector-transfected BxPC-3 cells was similar. The invasion cell number and the NF-kappaB activity were increased by GDNF stimulation. However, in the presence of MG132 or IkappaBalphaM, which blocks the nuclear localization of NF-kappaB, both were significantly suppressed. Furthermore, reduced activity of both remained unchanged by GDNF stimulation. CONCLUSION: These results indicate that GDNF promotes NF-kappaB activation and that the latter is involved in the invasive potential of human pancreatic cancer cells.

Cell Division↗
PubMed2004

Expression of integrins in tumour tissue of a patient with cancer of the Vater's ampulla complicated by pancreas divisum.

We present herein a rare case where cancer of the Vater's ampulla was complicated with pancreas divisum. Endoscopic retrograde cholangiopancreatography demonstrated the pancreas divisum and stenosis of the common channel due to the tumorous lesion of the Vater's ampulla. Magnetic resonance cholangiopancreatography demonstrated that the Wirsung duct and Santorini duct were unconnected. The biopsy specimen at the upper gastrointestinal endoscopy revealed moderately differentiated tubular adenocarcinoma. The patient was diagnosed with cancer of the Vater's ampulla complicated with pancreas divisum, and underwent a pylorus-preserving pancreaticoduodenectomy. Immunohistochemical examination showed that the p53 protein and the alpha5beta1-integrin were expressed in tumour cells, and the proliferating cell nuclear antigen test was positive. Furthermore, the alpha5beta1-integrin was expressed in chronic pancreatitis tissue. We demonstrate that there is a risk that pancreas divisum will co-exist with malignant disease in the pancreaticobiliary area, causing a potential risk of complicating malignant diseases in the pancreas.

Adenocarcinoma↗
PubMed2004

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between April 2002 and March 2003].

Tendency of isolated bacteria from infections in general surgery during the period from April 2002 to March 2003 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 334 strains were isolated from 131 (75.3%) of 174 patients with surgical infections. One hundred and seventy-one strains were isolated from primary infections, and 163 strains were isolated from post-operative infections. From primary infections, anaerobic Gram-positive bacteria were predominant, while aerobic Gram-positive bacteria were predominant from postoperative infections. Among aerobic Gram-positive bacteria, although the isolation rate of Staphylococcus aureus was the highest, followed by that of Enterococcus faecalis from primary infections, the isolation rate of E. faecalis was the highest from postoperative infections. Among anaerobic Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the highest from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order, and from postoperative infections, E. coli was the most predominantly isolated, followed by P. aeruginosa, Enterobacter cloacae, and Citobacter freundii. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. The isolation rate of aerobic Gram-negative bacteria from primary infections and that of aerobic Gram-positive bacteria from postoperative infections were high in the last several years. We noticed no vancomycin-resistant Gram-positive cocci nor P. aeruginosa producing metallo-beta-lactamase. But we noticed cefazolin-resistant E. coli probably producing extended spectrum beta-lactamase.

Anti-Bacterial Agents↗
PubMed2004

[The QOL of the patient with advanced pancreatic carcinoma was changed for the better with combination therapy consisting of arterial chemotherapy and injection of interferon].

The prognosis of advanced pancreatic carcinoma with multiple liver metastases is extremely poor. The current methods of treating pancreatic carcinoma are far from satisfactory. The results of systemic and regional chemotherapies for pancreatic carcinoma are disappointing. The patient was a 68-year-old male with advanced pancreatic carcinoma. After an operation, he received a combination therapy consisting of arterial infusion (gemcitabine hydrochloride, GEM, 600 mg) and muscle injection of interferon (IFN, 300x10(4) U). A decrease in metastatic tumor of the liver was observed. In this report, we describe the case of a patient whose effective results were achieved by using a new combination of GEM and IFN.

Aged↗
PubMed2004

[Management of intravascular catheters for prevention of perioperative cross infections].

Bloodstream infection derived from an intravascular catheter occupies an important position among the various types of nosocomial infection. It is therefore necessary to establish a system for preventing catheter infection not only as measures for each separate infection, but also for the entire hospital. Catheter infections are mainly caused by contamination of the connecting part of a transfusion line during the infusion of drug solution as well as by contamination of the part of the catheter inserted. Consequently, the greatest possible care should be taken in the preparation of aseptic transfusion and the prevention of contamination when connecting a transfusion line. In particular, there are problems with three-way stopcocks, management of hubs, frequency of transfusion line exchange, fat emulsion injection method, and blood preparation. It is most important to consider effective nutritional management methods that do not require the insertion of a central venous catheter.

Catheterization, Central Venous↗
PubMed2003

Calpain is involved in the HIV replication from the latently infected OM10.1 cells.

Treatment of OM10.1 cells latently infected with human immunodeficiency virus type 1 (HIV-1) with phorbol ester and calcium ionophore (A23187) induced virus replication which was blocked by N-Ac-Leu-Leu-norleucinal (ALLnL), a calpain inhibitor I, and not by lactacystin, a specific proteasome inhibitor. When the purified NF-kappa B/I kappa B complex was treated with mu-calpain, the specific DNA-binding activity was demonstrated by using electrophoretic mobility shift assay in vitro. This effect of mu-calpain was inhibited by ALLnL and calpastatin and not by lactacystin. In fact, we found that mu-calpain efficiently degraded I kappa B alpha. Furthermore, our Western blotting analysis has revealed that mu-calpain cleaves I kappa B alpha at its N-terminal and C-terminal regions that were previously reported to be involved in the interaction with NF-kappa B p65. These observations indicate that in monocyte/macrophage cells calcium signaling is involved in NF-kappa B activation through activation of calpain and thus calpain inhibitors may be effective in inhibiting the activation of latently infected HIV.

Acetylcysteine↗
PubMed2003

Enhancement of integrins by interleukin-1alpha, and their relationship with metastatic and invasive behavior of human pancreatic ductal adenocarcinoma cells.

BACKGROUND AND OBJECTIVES: Adhesion and invasion of tumor cells to extracellular matrix (ECM) proteins play an important role in tumor metastasis formation. We investigated the enhancement of adhesive and invasive behavior to ECM proteins of human pancreatic cancer cells by interleukin-1alpha (IL-1alpha) to examine the mechanism of adhesion and invasion of metastatic human pancreatic cancer cells to ECM proteins. METHODS: The enhancement of integrin subunits by IL-1alpha was examined by cellular enzyme-linked immunosorbent assay (CELISA) in two metastatic human pancreatic cancer cell lines (BxPC-3 and SW1990) and two nonmetastatic pancreatic cancer cell lines (PaCa-2 and PANC-1). In addition, assays of cancer cell adhesion and invasion to ECM proteins were performed to investigate whether increased integrin expression affected the invasive interaction between cancer cells and the putative integrin ECM ligands. RESULTS: Expression of the alpha6 subunit by metastatic cancer cells was enhanced by IL-1alpha. Metastatic cancer cells also exhibited preferential adherence and invasion to laminin compared with nonmetastatic cancer cells, and this was enhanced by IL-1alpha. CONCLUSIONS: The enhancement of alpha6beta1-integrin by Il-1alpha acting through IL-1RI, as well as the expression of alpha6beta1-integrin, plays an important role in metastasis formation in pancreatic cancer

Carcinoma, Ductal, Breast↗
PubMed2003

Cardiotrophin-1 is a prophylactic against the development of chronic hypoxic pulmonary hypertension in rats.

BACKGROUND: Cardiotrophin-1 (CT-1) reduces arterial blood pressure by activating nitric oxide synthesis. This study attempted to elucidate the effect of CT-1 on pulmonary arteries of pulmonary hypertensive rats. METHODS: Pulmonary hypertension was induced in rats in a hypoxic chamber containing 10% to 11% oxygen. Rats kept in the hypoxic environment received either recombinant mouse CT-1 at a concentration of 50 micro g/kg (CT-1+hypoxia group, n = 21) or phosphate-buffered saline (hypoxia group, n = 30) once per day. Control rats housed in room air also received either the equivalent concentration of CT-1 (CT-1+normoxia group, n = 18) or phosphate-buffered saline (normoxia group, n = 39). Pulmonary arterial pressure, pulmonary vasorelaxation, and ventricular hypertrophy were measured. RESULTS: The mean pulmonary arterial pressures were as follows (from lowest to highest; p values are relative to the hypoxia group): normoxia group (20.3 +/- 4.0 mm Hg, p < 0.0001), CT-1+normoxia group (21.1 +/- 2.4 mm Hg, p < 0.0001), CT-1+hypoxia group (27.9 +/- 4.1 mm Hg, p = 0.0019), and hypoxia group (33.9 +/- 6.6 mm Hg). The endothelium-dependent vasorelaxation value was largest in the normoxia group (59.5% +/- 17.4%, p < 0.0001), with it decreasing in the other groups in the following order (p values are relative to the hypoxia group): CT-1+normoxia group (52.8% +/- 15.5%, p = 0.0005), CT-1+hypoxia group (42.3% +/- 14.8%, p = 0.0061), and hypoxia group (17.4% +/- 4.8%). Right ventricular hypertrophy was significant only in the hypoxia group. CONCLUSIONS: Our results demonstrate that treatment with CT-1 in a chronic hypoxic pulmonary hypertension model protects the endothelial function of the pulmonary artery; decreases pulmonary arterial pressure; and attenuates right ventricular hypertrophy.

Analysis of Variance↗
PubMed2003

Expression and prognostic roles of integrins and interleukin-1 receptor type I in patients with ductal adenocarcinoma of the pancreas.

To investigate the prognostic indicator, we examined the expression of alpha6- and alpha5-integrin and interleukin-1 receptor type I (IL-1RI) immunohistochemically, and analyzed the correlation between immunohistochemical findings and clinicopathological factors in pancreatic cancer. In patients with a strongly expressing alpha6-integrin subunit or weakly expressing alpha5beta1-integrin in pancreatic cancer tissues there was a significant association with advanced TNM stage (P = 0.027 and 0.014, respectively), presence of liver metastases (P = 0.032 and 0.002, respectively), and poor prognosis (P = 0.0155 and 0.0056, respectively). In patients with a weakly expressing alpha6 integrin subunit or weakly expressing alpha5beta1-integrin in noncancerous pancreatic tissues there was a significant association with poor prognosis (P = 0.0324 and 0.0396, respectively). Multivariate analysis demonstrated that strong expression of alpha6- and weak expression of alpha5beta1-integrin were found to be independent prognosticators in pancreatic cancer patients. Our present results indicate that alpha6beta1- and alpha5beta1-integrin expression can be a significant prognostic indicator in pancreatic cancer.

Aged↗
PubMed2003

Keyhole procedure: a new technique for intestinal anastomosis with a large opening and less tissue trauma, using both circular and linear staplers.

BACKGROUND: We designed a new technique, termed the keyhole procedure, that uses a linear stapler to enlarge the anastomotic opening made with a circular stapler. The present study was performed to evaluate this technique in terms of maximum bursting pressure and area of anastomotic opening and compare it with conventional anastomosis using a circular stapler in an animal model. METHODS: Anastomoses were created by the new technique or by the conventional method in swine small intestine. Anastomosis integrity was assessed by the air leakage test. Anastomotic openings were photographed and measured with an image analyzer. RESULTS: It was found that the area of the anastomotic opening obtained with the new technique was more than 3 times that of the control (P <.001). There was no significant difference between the methods in maximum bursting pressure. CONCLUSIONS: The keyhole procedure provides a larger anastomotic opening than conventional anastomosis with a circular stapler, without impairing the integrity of anastomosis.

Anastomosis, Surgical↗