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Biomedical subjects

Shingo Ishiguro

Publications and source records attributed to Shingo Ishiguro.

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

Mitral valve repair for mitral insufficiency due to infective endocarditis in a patient with idiopathic thrombocytopenic purpura.

A 63-year-old woman with an 18-year history of idiopathic thrombocytopenic purpura (ITP) was admitted with a persistent fever of unknown cause. Blood culture was positive for alpha-Streptococcus and echocardiography revealed severe mitral regurgitation and vegetation on the mitral valve. After antimicrobial therapy for six weeks, she underwent mitral valve repair using a Cosgrove ring. The platelet count increased and remained stable by perioperative treatment with intravenous high-dose gamma-globulin and platelet transfusion without steroids therapy or splenectomy. The hospital course was uneventful. Perioperative high-dose gamma-globulin therapy and platelet transfusion for the cardiac operation were useful to increase and maintain the platelet count for an ITP patient complicated with infective endocarditis.

Endocarditis, Bacterial↗
PubMed2004

Attenuation by cyclic phosphatidic acid of peritoneal metastasis of azoxymethane-induced intestinal cancers in Wistar rats.

The effect of cyclic phosphatidic acid, a unique analogue of lysophosphatidic acid, on the induction of bombesin-enhanced peritoneal metastases from intestinal adenocarcinomas induced by azoxymethane was investigated in male Wistar rats. Rats were given 10 weekly injections of azoxymethane (7.4 mg/kg body weight, s.c.) and of bombesin (40 microg/kg body weight, s.c.) every other day from the start of the experiment, and from week 16, they received injections of cyclic phosphatidic acid (3 or 6 mg/kg body weight, s.c.) every other day until the end of the experiment in week 45. Cyclic phosphatidic acid at both dosages significantly decreased the incidence of bombesin-enhanced cancer metastases to the peritoneum but had little or no effect on the location, histologic type, depth of involvement or infiltrating growth patterns of the tumors. Cyclic phosphatidic acid at either dose decreased significantly the incidence of lymphatic vessel invasion of adenocarcinomas and the activity of RhoA protein in the tumors, both of which were enhanced by bombesin. Our findings indicate that cyclic phosphatidic acid inhibits cancer metastasis through inhibition of RhoA protein activation.

Adenocarcinoma↗
PubMed2004

Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study.

BACKGROUND: Depth of submucosal invasion (SM depth) in submucosal invasive colorectal carcinoma (SICC) is considered an important predictive factor for lymph node metastasis. However, no nationwide reports have clarified the relationship between SM depth and rate of lymph node metastasis. Our aim was to investigate the correlations between lymph node metastasis and SM depth in SICC. METHODS: SM depth was measured for 865 SICCs that were surgically resected at six institutions throughout Japan. For pedunculated SICC, the level 2 line according to Haggitt's classification was used as baseline and the SM depth was measured from this baseline to the deepest portion in the submucosa. When the deepest portion of invasion was limited to above the baseline, the case was defined as a head invasion. For nonpedunculated SICC, when the muscularis mucosae could be identified, the muscularis mucosae was used as baseline and the vertical distance from this line to the deepest portion of invasion represented SM depth. When the muscularis mucosae could not be identified due to carcinomatous invasion, the superficial aspect of the SICC was used as baseline, and the vertical distance from this line to the deepest portion was determined. RESULTS: For pedunculated SICC, rate of lymph node metastasis was 0% in head invasion cases and stalk invasion cases with SM depth <3000 micro m if lymphatic invasion was negative. For nonpedunculated SICC, rate of lymph node metastasis was also 0% if SM depth was <1000 micro m. CONCLUSIONS: These results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC.

Adult↗
PubMed2004

Unusual atrophic change after repeated arterial therapy for hepatocellular carcinoma: report of a case.

We report the case of a 45-year-old man with advanced hepatocellular carcinoma (HCC) who was able to undergo radical surgery after repeated transarterial therapy. Transarterial chemoembolization was repeated three times, and thereafter, transarterial infusion chemotherapy using Lipiodol was performed on the right hepatic artery. Because notable atrophy of the right lobe and compensated hypertrophy of the left lobe were detected after this therapy, an extended right lobectomy could be performed. Histologically, the HCC showed complete necrosis. The remarkable atrophic change of the right lobe was thought to be due to an obstruction of the right portal veins by the spread of inflammation around the bile duct necrosis, in addition to the narrowing of the hepatic artery. A thorough understanding of this phenomenon and the development of methods to clinically apply it in the treatment of cancer patients may thus lead to an increase in the percentage of resectable cases of advanced HCC.

Atrophy↗
PubMed2004

Mucin phenotypic expression and background mucosa of esophagogastric junctional adenocarcinoma.

BACKGROUND: In the West, the incidence of adenocarcinoma of the cardia or esophagogastric junction (EGJ) is increasing. This carcinoma is variously defined, however, and it contains heterogeneous tumors. In Japan, the frequency of this carcinoma is low, and little is known about it. We studied small esophagogastric junctional adenocarcinoma to determine its characteristics in Japanese patients. METHODS: Fifty-four patients with Siewert type II junctional adenocarcinoma (with tumors <<4 cm in maximum diameter) were studied. The carcinomas were classified into two types: tumors straddling the EGJ (EGJ-type) and tumors occurring entirely below the EGJ (bEGJ-type). Characteristics of the tumors and surrounding mucosae were evaluated. Phenotypic expression of mucin, p53 overexpression, and Helicobacter pylori infection were investigated histologically and immunohistochemically. RESULTS: Twenty-three (43%) patients had EGJ-type and 31 (57%) had bEGJ-type carcinomas. The ratio of advanced cancers was significantly higher in EGJ-type. Some between-group similarities and differences existed in histological type, mucin phenotype, and p53 protein overexpression, but they were not statistically significant. In the mucosa surrounding EGJ-type tumors vs bEGJ-type tumors, oxyntic glands were significantly better preserved, gastric intestinal metaplasia occurred significantly less frequently, and the H. pylori infection rate was lower. Barrett's metaplasia was seen in only 2 patients, with the EGJ-type. CONCLUSION: EGJ-type and bEGJ-type adenocarcinomas have different background mucosa of the stomach. EGJ-type has less atrophy of the oxyntic glands and less intestinal metaplasia in the stomach. This type appears to be the Western-type junctional adenocarcinoma that is still rare in Japan. Many cases of advanced junctional adenocarcinoma in Japan are of subjunctional origin.

Adenocarcinoma↗
PubMed2004

Interleukin-6/soluble interleukin-6 receptor signaling attenuates proliferation and invasion, and induces morphological changes of a newly established pleomorphic malignant fibrous histiocytoma cell line.

Pleomorphic malignant fibrous histiocytoma (MFH) is occasionally associated with inflammatory paraneoplastic syndrome (PNS). Recently, we reported that interleukin (IL)-6, one of the candidate cytokines, which induces such systemic inflammatory reaction, may be a tumor-associated factor involved in the pathogenesis and its clinical manifestations of MFH. In the local microenvironment, tumor-induced inflammatory reaction may play a role favoring tumor progression. To clarify the biological relevance of IL-6 in MFH, we established a human MFH cell line, named MIPS-2, derived from a resected specimen of a patient presenting with PNS. In this patient, the serum IL-6 level ran parallel to the disease course: elevated serum IL-6 concentration normalized immediately after radical surgery, and re-elevation occurred on tumor recurrence. MIPS-2 presented pleomorphic appearance, severe nuclear abnormalities with prominent nucleoli, and tumorigenesis in nude mice. MIPS-2 expressed IL-6, IL-6 receptor (IL-6R), and glycoprotein 130 (gp130) but lacked the soluble form of IL-6R (sIL-6R), as determined by flow cytometry and reverse transcriptase-polymerase chain reaction analyses. Stimulation of MIPS-2 with IL-6 combined with exogenous sIL-6R induced phosphorylation of both signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK), decreased cell proliferation, attenuated invasion, and induced morphological changes. Collectively, these data suggested that the IL-6/sIL-6R signaling pathway plays a pivotal role for proliferation, invasion, and morphology of MFH via STAT3 and MAPK pathway as autocrine and/or paracrine manner, and proposed the therapeutic potential for the use of both anti-growth factor and proinflammatory cytokine-targeting strategies to combat devastating MFH.

Adult↗
PubMed2004

Congenital pericardial defect associated with ruptured type A aortic dissection.

Congenital pericardial defect is a rare and little-known anomaly. Here we describe the unique clinical presentation of a 64-year-old man with partial defect of the left pericardium associated with ruptured acute type A aortic dissection manifesting massive left hemothorax. In this patient, the pericardial defect played the role of a pericardial draining window, which incidentally prevented the heart from cardiac tamponade. Emergent surgery was successfully performed with a prosthetic graft replacement.

Aortic Dissection↗
PubMed2004

Myxoid liposarcoma with adipocytic maturation: detection of TLS/CHOP fusion gene transcript.

This report describes a 49-year-old woman with a well-circumscribed nodule of liposarcoma. The patient noticed a soft, slowly growing mass at the right sural region. Both axial computed tomography and magnetic resonance imaging revealed a soft tissue tumor consisting of nonfatty lesion measuring 5 x 3 x 3 cm circumscribed by a 1-cm thickened fatty area. Histologically, the tumor was made of 2 distinct components: the inner component of the tumor was a classic myxoid liposarcoma with numerous lipoblasts; the outer component was a lipoma-like lesion consisting of mature adipocytes without atypical nuclei. Immunohistochemically, MDM2 overexpression was observed and p53 immunophenotype was negative in both components. Molecular analysis revealed that type 1 TLS/ CHOP fusion gene transcript, characteristic of myxoid/round cell liposarcoma, was detected in both areas.

Adipocytes↗
PubMed2004

New indication for endoscopic treatment of colorectal carcinoma with submucosal invasion.

BACKGROUND AND AIMS: Although an increasing number of early colorectal cancers (CRC) have been curatively treated by endoscopy, there have been no definitive criteria to decide the effectiveness of such therapy. We retrospectively analyzed clinicopathological factors to establish criteria for curative endoscopic treatment of early CRC. METHODS: First, risk factors of lymph node metastasis were analyzed in 171 patients who received surgery with postoperative histology of CRC submucosal invasion. The resultant new criteria were evaluated in another 60 patients who experienced endoscopic resection of CRC and surgery according to the current criteria most often used in Japan. RESULTS: In the first substudy, lymph node metastasis was present in 18 of 171 patients (10.5%). Lymphatic permeation, sprouting and infiltrative growth of cancer cells were identified as histological factors significantly related to lymph node metastasis, and observed in much higher rates when the depth of submucosal invasion was beyond 1,500 micron. The minimum depth with positive lymph nodes was 1,075 micron. In the second group of 60 patients, lymph node metastasis was recorded in none of nine patients who met our new criteria of complete endoscopic treatment: submucosal invasion below 1,500 micron in depth, and no lymphatic permeation, sprouting or infiltrative growth pattern on tumor histology. Lymph node metastasis was positive in three of the other cases who did not meet our new criteria. CONCLUSIONS: The present study showed that endoscopic treatment of early CRC may be considered complete when submucosal invasion beyond 1,500 micron, lymphatic permeation, sprouting, and infiltrating growth are all denied.

Adult↗
PubMed2003

Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and gamma-glutamyl carboxylase) gene variants with warfarin sensitivity.

We analyzed mutations of 7 vitamin K-dependent protein and cytochrome P450 2C9 genes in 45 patients and investigated whether any contribute to the large interpatient variability in the warfarin dose-effect relationship. Total clearance and daily dose, INR and INR/Cp, were used as pharmacokinetic and pharmacodynamic indexes, respectively. Patients were grouped by genotype based on a single polymorphism and combinations of polymorphisms. Among the 30 sequence variants identified, CYP2C9*3, 165Thr-->Met of the factor II gene, -402G-->A, (37-bp repeat)n, and -746T-->C of the factor VII gene, and (CAA repeat)n of the gamma-glutamyl carboxylase gene were selected as candidate polymorphisms. As the analysis of single polymorphisms implied, the highest INR/Cp mean values and the lowest warfarin maintenance doses were observed in patients homozygous for the 165Met, -402G, (37-bp repeat)6 and -746T alleles. Multiple regression analysis revealed that warfarin sensitivity was independently associated with -402G-->A, (CAA repeat)n, CYP2C9*3, and 165Thr-->Met, which accounted for 50% of variance. These results suggest that part of the considerable interpatient variation is attributable to genetic variation, and the combined genotyping of CYP2C9 and certain vitamin K-dependent protein genes is useful for predicting anticoagulant responses.

Anticoagulants↗
PubMed2003

Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation.

OBJECTIVE: To characterize the radiological and clinicopathologic features of cystic synovial sarcoma. DESIGN AND PATIENTS: Seven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed. RESULTS: CT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma. CONCLUSION: All cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging.

Adolescent↗
PubMed2003

Enhancement by interleukin-1 beta of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats: a possible mechanism for Helicobacter pylori-associated gastric carcinogenesis.

The effect of prolonged administration of the cytokine interleukin (IL)-1beta on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was examined in Wistar rats. In addition, we examined the effects on the proliferating cell nuclear antigen (PCNA) labeling index and the hepatocyte growth factor (HGF) immunoreactivity of the gastric mucosa. The rats received intraperitoneal injections of 0.1 or 0.3 microg/kg body weight of IL-1beta every other day after oral treatment with MNNG for 25 weeks. Long-term administration of IL-1beta at high dose, but not at low dose, significantly increased the incidence of gastric cancer in week 52. Administration of IL-1beta at high dose also significantly increased the labeling index and the HGF immunoreactivity of the gastric antral mucosa, and induced inflammatory cell infiltration and glandular atrophy of the gastric mucosa. Because IL-1beta production in the gastric mucosa is increased in patients with Helicobacter pylori-associated gastritis and eradiation of the organism significantly decreases the IL-1beta production, these findings suggest that Helicobacter pylori-associated gastric carcinogenesis may be in part mediated through IL-1beta.

Adenocarcinoma↗
PubMed2003

Auxiliary partial orthotopic liver transplantation for fulminant hepatitis: regeneration of the diseased native liver in a pig model.

BACKGROUND: This study was performed to develop a clinically relevant porcine model of auxiliary partial orthotopic liver transplantation (APOLT) for fulminant hepatic failure. METHODS: FHF was induced by intraportal administration of alpha-amanitin and lipopolysaccharide. Thereafter, pigs were divided into four groups. Group 1 was an untreated, control group. In group 2, pigs underwent only a left hemihepatectomy. Pigs in groups 3 and 4 received APOLT after hemihepatectomy. Tacrolimus was administered to pigs in group 4, but not to those in group 3. RESULTS: Two-week survival rates were 0%, 20%, 40%, and 100% for groups 1, 2, 3, and 4, respectively. In group 4, after abolishing the graft function at 1 week, pigs survived for more than 2 weeks, and regeneration of the native liver was confirmed histologically. CONCLUSIONS: Pigs suffering from fulminant hepatic failure could achieve long survival and liver regeneration with a temporary support of the auxiliary graft.

Animals↗
PubMed2003

Coordinate induction of AMP deaminase in human atrium with mitochondrial DNA deletion.

Despite the heteroplasmic lower population of mitochondrial (mt) DNA deletion, mtDNA deletion is significantly related to the loss of atrial adenine nucleotides. To elucidate its mechanism, we examined the frequency of a 7.4-kb mtDNA deletion, the concentration of adenine nucleotides, and the activity of AMP catabolic enzymes in 10 human right atria obtained from cardiac surgery, using quantitative PCR, HPLC, and immunoprecipitations. The atrial concentrations of ATP, ADP, AMP, and the total adenine nucleotides were significantly lower in patients with deletion than those in patients without deletion, despite the lower frequency of their deletion. The activities of total AMP deaminase (AMPD), liver-type (AMPD 2), and heart-type isoform (AMPD 3) were significantly higher in patients with deletion than in patients without deletion, although there was no significant difference in the cytosolic 5(')-nucleotidase among them. In conclusion, mtDNA deletion coordinately induces AMP deaminase to contribute to the loss of atrial adenine nucleotides through degrading AMP excessively.

AMP Deaminase↗
PubMed2003

Prognostic significance of the size of cancer nests in metastatic lymph nodes in human esophageal cancers.

BACKGROUND: Postoperative survival of patients with esophageal cancers after curative surgery is strongly affected by the presence of lymph node metastasis. The number and location of lymph node metastases have been evaluated and graded, but the clinical significance of their size has not been well investigated. METHODS: Of 322 esophageal cancer patients who underwent curative operations with radical lymph node dissection, 170 (53%) had lymph node metastasis. A total of 784 metastatic lymph nodes were obtained, and the area of the cancer nests was measured microscopically in the cross section. The data from each patient included the area of the largest cancer nest in the positive nodes (Nmax), classified as Na (<4 mm2), Nb (4-25 mm2), Nc (25-100 mm2), or Nd (>100 mm2). RESULTS: The 170 patients were classified according to the Nmax value: Na, 31 (18.2%); Nb, 35 (20.5%); Nc, 49 (28.8%); and Nd, 55 (32.4%). The 5-year survival rate was 77.7% in patients without lymph node metastasis and 35.4% in those with lymph node metastasis. When classified by Nmax, the 5-year survival rate was 77.8% for Na, 63.9% for Nb, 18.8% for Nc, and 12.8% for Nd. There was no significant difference in the survival rate between Na patients and those without lymph node metastasis. Nmax showed significant correlation with the primary tumor size, depth of tumor invasion, and number and location of metastatic lymph nodes, but not with histologic type or primary tumor location. In multivariate analysis, the Nmax value, the number of lymph node metastases and depth of tumor invasion were independent prognostic factors, while the location of the lymph node metastases was not statistically significant. CONCLUSIONS: The area of the largest cancer nest in the lymph nodes was one of the most significant prognostic factors for esophageal cancers. This estimation is objective and reproducible and may be of great importance when deciding the therapeutic modality for patients with esophageal cancers.

Esophageal Neoplasms↗
PubMed2003

Large-animal models of fulminant hepatic failure.

For the development of an artificial liver support system, a clinically relevant large-animal model of fulminant hepatic failure (FHF) is indispensable. Although several large-animal models have been reported so far, they have not been entirely satisfactory. Recently, we have developed a new porcine model of FHF by means of intraportal administration of 0.1 mg/kg of alpha-amanitin and 1 microg/kg of lipopolysaccharide (LPS). This model has the following superior features: 100% mortality within 5 days along with a marked elevation of aspartate transaminase (AST) levels to around 10,000 IU/l, and severe metabolic disorders such as serum lactate accumulation, hypoglycemia, coagulopathy, plasma amino acid imbalance, and hyperammonemia; an onset of hepatic encephalopathy and a significant increase in intracranial pressure immediately before death; a reversal of FHF by orthotopic liver transplantation, proving that the toxicity is liver-specific and that the graft liver is unaffected; and the capability of the damaged liver to recover and achieve both morphological and functional regeneration in 1 week if supported by an efficient auxiliary graft. Because this porcine model satisfies many of the required criteria of an optimal FHF model, it is expected to provide a useful tool for the study of FHF and the development of new therapies.

Amanitins↗