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Biomedical subjects

H Imamura

Publications and source records attributed to H Imamura.

At least 145 records · Page 8Linked to original sources

Prognostic significance of anatomical resection and des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma.

BACKGROUND: Portal venous tumour extension and intrahepatic metastasis result in a poor prognosis following hepatectomy for hepatocellular carcinoma (HCC). Anatomical resection is, in theory, preferable for eradicating these types of invasion. Des-gamma-carboxy prothrombin (DCP) has been reported to be associated with adverse pathological variables. This study investigated the significance of anatomical resection and DCP as predictive factors for postoperative recurrence of HCC. METHODS: A retrospective cohort study was carried out in 138 consecutive patients who underwent hepatectomy for HCC smaller than 5 cm using the Cox proportional hazards model. RESULTS: Eight factors were univariately related to poor prognosis (in decreasing order of hazard ratio): intrahepatic metastasis, multiple tumours, alpha-fetoprotein 32 ng/ml or more; DCP greater than 0.1 arbitrary units (AU), tumour-exposed surgical margin, vascular invasion, non-anatomical resection and tumour 2.5 cm or more. Three variables (DCP, vascular invasion and tumour-exposed surgical margin) were excluded by a stepwise procedure in multivariate analysis. Although DCP was not an independent prognostic factor, a model replacing intrahepatic metastasis with DCP showed similar predictive accuracy in a receiver-operating characteristic curve. CONCLUSION: Anatomical resection appeared to have a beneficial effect on recurrence-free survival after hepatectomy for HCC. DCP measurement was effective in predicting HCC recurrence and had the advantage that it can be assessed before operation.

Biomarkers↗

Interleukin-1alpha stimulated prostacyclin release by increasing gene transcription of prostaglandin H synthase and phospholipase A2 in human vascular endothelial cells.

This study was conducted to evaluate the effects of interleukin-1alpha (IL-1alpha) on prostacyclin (PGI2) production in cultured human vascular endothelial cells in association with intracellular Ca2+, inositol 1,4,5-trisphosphate (IP3), and with prostaglandin H synthase (PGHS) and phospholipase A2 (PLA2) gene expression by using the competitive polymerase chain reaction (PCR) method. IL-1alpha did not increase PGI2 production for 15 min, but induced an increase of about three-fold relative to that in controls at 60 and 180 min. IL- 1alpha had no effect on intracellular Ca2+ levels throughout the experimental period. In this study, consistent with previous reports, PGHS-1 messenger RNA (mRNA) was constitutively expressed, whereas PLA2 mRNA was not. After stimulation with IL-1alpha, PLA2 mRNA level showed an eightfold increase within 15 min, and PGHS-2 mRNA level increased by 76-fold within 180 min. PGHS-1 mRNA level was increased 1.6-fold at 180 min. These results suggest the existence of regulatory mechanisms of IL-1alpha-induced PGI2 production, which involve PGHS and PLA2 gene transcription.

Base Sequence↗

Oxygen uptake, heart rate, and blood lactate responses during and following karate training.

PURPOSE: The purpose of this study was to examine whether each exercise and an entire karate training session can achieve: 1) accepted training intensity thresholds for effective aerobic capacity training, 2) energy expenditure (EE) thresholds for total body mass and fat weight loss, and 3) elevation in excess postexercise oxygen consumption (EPOC). METHODS: We investigated physiological responses during five types of karate training: basic techniques without (S-Basics) and with (M-Basics) movements, sparring techniques without (TECH I) and with (TECH II) an opponent, and kata. RESULTS: The mean percent of maximal oxygen uptake (%VO2max) and HR (%HRmax) for S-Basics were below the accepted threshold (60% of HRmax or 50% of VO2max) and for M-Basics, TECH I and TECH II were above the threshold for increasing VO2max. For kata and the entire 70 min of karate training, the mean %HRmax were slightly above the threshold, and %VO2max were slightly below the threshold. The mean EPOC measured for 5 min immediately following 70 min of karate training did not differ from the resting VO2. The mean EE resulting from 70 min of karate exercise and EPOC were 2355.4+/-316.3 kJ and 38.8+/-32.7 kJ, respectively. CONCLUSIONS: Although the training intensity of karate exercises studied was moderate and the effects of karate training on EPOC were minimal, the mean value of EE was well above the accepted threshold for total body mass and fat weight loss.

Adult↗

Carbapenem derivatives as potential inhibitors of various beta-lactamases, including class B metallo-beta-lactamases.

A variety of 1beta-methylcarbapenem derivatives were screened to identify inhibitors of IMP-1 metallo-beta-lactamase, a class B beta-lactamase, in an automated microassay system using nitrocefin as a substrate. The structure-inhibitory-activity relationship study revealed that three types of 1beta-methylcarbapenems having benzothienylthio, dithiocarbamate, or pyrrolidinylthio moieties at the C-2 position showed good inhibitory activity. Among the compounds screened, J-110,441, having a benzothienylthio moiety at the C-2 position of 1beta-methylcarbapenem, was the most potent inhibitor of class B metallo-beta-lactamases with K(i) values of 0. 0037, 0.23, 1.00, and 0.83 microM for IMP-1 encoded by the bla(IMP) gene, CcrA from Bacteroides fragilis, L1 from Stenotrophomonas maltophilia, and type II from Bacillus cereus, respectively. In a further characterization study, J-110,441 also showed inhibitory activity against TEM-type class A serine beta-lactamase and chromosomal class C serine beta-lactamase from Enterobacter cloacae with K(i) values of 2.54 and 0.037 microM, respectively. Combining imipenem or ceftazidime with J-110,441 had a synergistic effect on the antimicrobial activity against beta-lactamase-producing bacteria. Against the isolates of IMP-1-producing Serratia marcescens, the MICs of imipenem decreased to levels ranging from 1/64 to 1/4 in the presence of one-fourth of the MIC of J-110,441. Against E. cloacae producing high levels of class C beta-lactamase, the MIC of ceftazidime decreased from 64 to 4 microg/ml in the presence of 4 microg of J-110,441 per ml. This is the first report to describe a new class of inhibitor of class B and class C beta-lactamases including transferable IMP-1 metallo-beta-lactamases.

Bacterial Proteins↗

Pseudoaneurysm of the left ventricle progressing from a subepicardial aneurysm.

A 56-year-old man presented with an inferior myocardial infarction and a huge pseudoaneurysm below the inferior surface of the left ventricle, which had progressed from a small subepicardial aneurysm over a 6-month period. Transthoracic echocardiography, Doppler color flow images, radionuclide angiocardiography, magnetic resonance imaging and contrast ventriculography all revealed an abrupt disruption of the myocardium at the neck of the pseudoaneurysm, where the diameter of the orifice was smaller than the aneurysm itself, and abnormal blood flows from the left ventricle to the cavity through the orifice with an expansion of the cavity in systole and from the cavity to the left ventricle with the deflation of the cavity in diastole. Coronary angiography revealed 99% stenosis at the atrioventricular nodal branch of the right coronary artery. At surgery the pericardium was adherent to the aneurysmal wall and a 1.5-cm orifice between the aneurysm and the left ventricle was seen. Pathological examination revealed no myocardial elements in the aneurysmal wall. The orifice was closed and the postoperative course was uneventful. Over-intense physical activity as a construction worker was considered to be the cause of the large pseudoaneurysm developing from the subepicardial aneurysm. These findings indicate that a subepicardial aneurysm may progress to a larger pseudoaneurysm, which has a propensity to rupture, however, it can be surgically repaired.

Aneurysm, False↗

Pulmonary embolism due to right ventricular thrombus in a case of Behcet's disease.

Right ventricular thrombus is a very rare manifestation of cardiovascular Behcet's disease. A 25-year-old man was admitted to hospital due to cough and fever of unknown origin. He experienced repetitive pulmonary embolism due to a right ventricular thrombus, which was surgically removed. A diagnosis of Behcet's disease was made based on his clinical course and the histological findings of the right ventricular wall and the skin lesion. He was quickly relieved of his symptoms after warfarinization and cyclosporine therapy.

Adult↗

Proximal bile duct stricture disguised as malignant neoplasm.

BACKGROUND: Discrimination of malignant proximal bile duct (PBD) stricture from a benign lesion is difficult with nonsurgical methods; indeed, 8% to 13% of PBD strictures prove to be benign after histologic examination of the surgically resected specimen. METHODS: In a 7-year period 178 patients with PBD stricture were admitted, and 99 of them underwent radical resection for presumably malignant lesions. In 14 of these patients the stenotic lesions were proved to be benign by postoperative histologic assessment. We reviewed these patients retrospectively by collecting data from their charts. RESULTS: Preoperative radiologic findings including cholangiography and angiography were compatible with malignancy in all 14 patients. Preoperative histologic studies suggested malignancy in 2 of 8 examined. Findings at laparotomy could not allow differentiation between malignant and benign lesions in any of the patients and strongly suggested malignancy in 3. Histologic examination of the resected specimens revealed extensive fibrosis with inflammatory cellular infiltration in all patients. There was 1 episode of significant morbidity postoperatively (transient cholangitis) but no mortality. CONCLUSION: Benign PBD strictures, although rare, are usually indistinguishable from malignant PBD strictures by preoperative or perioperative investigation. Given the minimal morbidity, all PBD strictures should be presumed malignant and managed accordingly, even at the risk of overtreating some benign cases.

Aged↗

Selectins induced by interleukin-1beta on the human liver endothelial cells act as ligands for sialyl Lewis X-expressing human colon cancer cell metastasis.

We have previously reported that colon cancer cells metastasized to the liver expressed an increased amount of sialyl Lewis X (SLeX) antigen compared to their corresponding primary lesions. It is now well known that SLeX antigen and sialyl Lewis A (SLeA) antigen are ligands for the selectins expressed on the endothelial cells. Therefore, it is assumed that SLeX-rich colon cancer cells could be easily adhered to the endothelial cells that express selectins. In this report we have tried to induce selectin expression on the human liver sinusoidal endothelial cells and have examined the adhesion of SLeX-high or -low expressing colon cancer cells to the interleukin-1beta (IL-1beta)-treated liver specimens using Stamper-Woodruff assay. These human colon cancer cells are termed KM12HX or KM12LX cells, respectively. A significantly increased number of KM12HX cells adhered to the IL-1beta-treated liver specimens compared to KM12LX cells. The adhesion of KM12HX cells was inhibited by the pretreatment of tumor cells with anti-SLeX antibody or by the pretreatment of liver specimens with anti-selectin antibodies. Selectin expression on the liver sinusoidal endothelial cells and endothelial cells of blood vessels after IL-1beta treatment was confirmed by immunohistochemically using anti-selectin monoclonal antibodies (MAbs). These findings strongly suggest that SLeX-expressing cancer cells could adhere to the sinusoidal endothelial cells via an SLeX-selectin interaction system and this could be a first step for colon cancer cells that metastasize to the liver. The mechanism by which these selectins can be induced in vivo is the next problem to be considered.

Cells, Cultured↗

Interaction of Bnr1p with a novel Src homology 3 domain-containing Hof1p. Implication in cytokinesis in Saccharomyces cerevisiae.

Proteins containing the formin homology (FH) domains FH1 and FH2 are involved in cytokinesis or establishment of cell polarity in a variety of organisms. We have shown that the FH proteins Bni1p and Bnr1p are potential targets of the Rho family small GTP-binding proteins and bind to an actin-binding protein, profilin, at their proline-rich FH1 domains to regulate reorganization of the actin cytoskeleton in the yeast Saccharomyces cerevisiae. We found here that a novel Src homology 3 (SH3) domain-containing protein, encoded by YMR032w, interacted with Bnr1p in a GTP-Rho4p-dependent manner through the FH1 domain of Bnr1p and the SH3 domain of Ymr032wp. Ymr032wp weakly bound to Bni1p. Ymr032wp was homologous to cdc15p, which is involved in cytokinesis in Schizosaccharomyces pombe, and we named this gene HOF1 (homolog of cdc 15). Both Bnr1p and Hof1p were localized at the bud neck, and both the bnr1 and hof1 mutations showed synthetic lethal interactions with the bni1 mutation. The hof1 mutant cells showed phenotypes similar to those of the septin mutants, indicating that HOF1 is involved in cytokinesis. These results indicate that Bnr1p directly interacts with Hof1p as well as with profilin to regulate cytoskeletal functions in S. cerevisiae.

Actins↗

Acinic Cell Adenocarcinoma Arising in the Breast of a Young Male: A Clinicopathological, Immunohistochemical and Ultrastructural Study.

A 23-year-old man with acinic cell adenocarcinoma of the breast is reported. He presented with a 4.8 x 4.2 cm mass in his left breast, and excisional biopsy was performed. Under the light microscope, tumor cells had abundant periodic acid-Schiff-positive secretory granules and eosinophlic cytoplasms. Electron microscopy revealed the granules to have various electron densities, a finding characteristic of acinic cell adenocarcinoma. Immunohistochemically, the tumor cells were stained with salivary-type amylase. Electron microscpic and immunohistochemical investigation greatly facilitated the diagnosis of this acinic cell adenocarcinoma, which was in an unusual location. We believe this is the first case report of acinic cell adenocarcinoma of the mammary gland studied utilizing light microscopic, ultrastructural and immunohistochemical techniques.

Journal Article↗

Interaction of radixin with Rho small G protein GDP/GTP exchange protein Dbl.

The Rho small G protein family, consisting of the Rho, Rac, and Cdc42 subfamilies, regulates various actin cytoskeleton-dependent cell functions. The Rho subfamily members regulate ERM (ezrin, radixin and moesin)-dependent association of the actin cytoskeleton with the plasma membrane. Moreover, the N-terminal regions of ERM interact with Rho GDI, an inhibitory regulator of all the Rho family members, and reduce its inhibitory action, finally initiating the activation of the Rho family members. We show here that the N-terminal region of radixin furthermore interacts with Dbl, a stimulatory GDP/GTP exchange protein of the Rho family members. This interaction does not affect the Dbl activity to stimulate the GDP/GTP exchange reaction of RhoA, a member of the Rho subfamily. Dbl does not interact with radixin which is precomplexed with Rho GDI, and Rho GDI displaces Dbl from radixin. Thus, radixin plays an important role in activation of the Rho family members by recruiting their positive and negative regulators.

Binding Sites↗

A subcloned human esophageal squamous cell carcinoma cell line with low thrombomodulin expression showed increased invasiveness compared with a high thrombomodulin-expressing clone--thrombomodulin as a possible candidate for an adhesion molecule of squamous cell carcinoma.

Thrombomodulin (TM) is an endothelial cell surface glycoprotein which converts thrombin from a procoagulant protease to an anticoagulant. We have previously reported that TM is a useful marker for immunohistochemical diagnosis of angiogenic tumors and also have reported that TM is expressed on squamous cell carcinoma (SCC) of the human esophagus. In addition, the expression of TM is significantly decreased in metastatic foci in lymph nodes compared with that in primary lesions. In order to reveal the biological significance of TM in SCC, we subcloned and established two different cell lines, i.e. TM-high-expressing (TE3HTM) cells and TM-low-expressing (TE3LTM) cells, from a human SCC cell line, TE3, using fluorescence-activated cell sorter (FACS) and examined the biological characteristics of these variant cell lines. These tumor cells revealed very similar morphological figures in ordinary cultured conditions and showed almost equal growth rates under various cultured conditions. By the invasion assay of these tumor cells using matrigel, we found that TE3LTM cells showed significantly increased invasive ability compared with that of TE3HTM cells. Characteristic intercellular localization of TM and a different manner of invasiveness between TE3LTM cells and TE3HTM cells suggest that TM may act as a cell-to-cell interaction molecule.

Carcinoma, Squamous Cell↗

Interaction of Rho1p target Bni1p with F-actin-binding elongation factor 1alpha: implication in Rho1p-regulated reorganization of the actin cytoskeleton in Saccharomyces cerevisiae.

The RHO1 gene encodes a homolog of mammalian RhoA small G protein in the yeast Saccharomyces cerevisiae. We have shown that Bni1p is one of the downstream targets of Rho1p and regulates reorganization of the actin cytoskeleton through the interaction with profilin, an actin monomer-binding protein. A Bni1p-binding protein was affinity purified from the yeast cytosol fraction and was identified to be Tef1p/Tef2p, translation elongation factor 1alpha (EF1alpha). EF1alpha is an essential component of the protein synthetic machinery and also possesses the actin filament (F-actin)-binding and -bundling activities. EF1alpha bound to the 186 amino acids region of Bni1p, located between the FH1 domain, the proline-rich profilin-binding domain, and the FH2 domain, of which function is not known. The binding of Bni1p to EF1alpha inhibited its F-actin-binding and -bundling activities. The BNI1 gene deleted in the EF1alpha-binding region did not suppress the bni1 bnr1 mutation in which the actin organization was impaired. These results suggest that the Rho1p-Bni1p system regulates reorganization of the actin cytoskeleton through the interaction with both EF1alpha and profilin.

Actins↗

Incessant ventricular fibrillation attacks in a patient with Brugada syndrome.

A 42-year-old man was hospitalized for investigation of repeated episodes of ventricular fibrillation (Vf). Electrocardiogram (ECG) showed typical features of Brugada syndrome. Echocardiography, coronary angiography and endomyocardial biopsy specimen were normal. 123I-MIBG scintigraphy showed homogeneous reduction of uptake. The patient demonstrated 17 episodes of Vf in 1 day, but these were terminated by direct cardioversion. Spectral analysis of heart rate variability demonstrated increased sympathetic activity followed by Vf attacks.

Adult↗

Interactions of drebrin and gephyrin with profilin.

Profilin is an actin monomer-binding protein which stimulates actin polymerization. Recent studies have revealed that profilin interacts with VASP, Mena, Bnilp, Bnrlp, and mDia, all of which have the proline-rich domain. Here, we isolated three profilin-binding proteins from rat brain cytosol by glutathione S-transferase-profilin affinity column chromatography and identified them as Mena, drebrin, and gephyrin. These proteins had a proline-rich domain and directly interacted with profilin.

Amino Acid Sequence↗

Isolation and characterization of a novel actin filament-binding protein from Saccharomyces cerevisiae.

We purified a novel actin filament (F-actin)-binding protein from the soluble fraction of Saccharomyces cerevisiae by successive column chromatographies by use of the 125I-labeled F-actin blot overlay method. The purified protein showed a minimum Mr of about 140 kDa on SDS-polyacrylamide gel electrophoresis and we named it ABP140. A search with the partial amino acid sequences of ABP140 against the Saccharomyces Genome Database revealed that the open reading frame of the ABP140 gene (ABP140) corresponded to YOR239W fused with YOR240W by the +1 translational frame shift. The encoded protein consisted of 628 amino acids with a calculated Mr of 71,484. The recombinant protein interacted with F-actin and showed the activity to crosslink F-actin into a bundle. Indirect immunofluorescence study demonstrated that ABP140 was colocalized with both cortical actin patches and cytoplasmic actin cables in intact cells. However, elimination of ABP140 by gene disruption did not show a deleterious effect on cell growth or affect the organization of F-actin. These results indicate that ABP140 is not required for cell growth but may be involved in the reorganization of F-actin in the budding yeast.

Actins↗

[An experimental study of local chemotherapy for metastatic lung tumor--isolated lung perfusion and pulmonary artery infusion].

PURPOSE: We evaluated the efficacy of local chemotherapy using isolated lung perfusion (ILP) and pulmonary artery infusion (PAI) in vivo to improve prognosis for patients with metastatic lung diseases. MATERIAL AND METHODS: Male F344 rats were used. The left lung was isolated and chemotherapeutic agents were administrated to the isolated lung by the ILP or PAI technique. Agents used were cisplatin (CDDP) and fluorouracil (5-FU), and their levels in the perfused lung and serum were measured (renal levels were also measured in CDDP groups). The results were compared with those obtained following intravenous administration (i.v.). In the ILP group, the left pulmonary artery and vein were clamped during perfusion. The agents were infused from the pulmonary artery, and the perfusate was collected from the pulmonary venotomy site following flushing with saline before declamping. In the PAI group, the left pulmonary artery was clamped and perfused with 0.2 ml of the agents, pulmonary arterial flow was occluded for 20 minutes, and perfusate was not collected. Rats were sacrificed 5 minutes after declamping in both groups, and the perfused lung and blood (and also kidneys in the CDDP group) were collected for pharmacokinetic examination. Histological examination of the perfused lung was also performed. RESULTS: In the ILP group treated with 1 mg of CDDP and PAI group treated with 0.1 mg of CDDP administration, the lung CDDP levels were significantly higher and the serum and renal CDDP levels were significantly lower than those in the IV group. In the ILP group treated with 150 mg of 5-FU and PAI group treated with 10 mg of 5-FU, the lung 5-FU levels were significantly higher than those in all IV groups and the serum 5-FU levels were lower than those in the IV group treated with 10 mg and 15 mg of 5-FU. The bronchopulmonary construction was histologically maintained in the perfused lung in each group. CONCLUSION: We concluded that local chemotherapy using ILP or PAI could be a safe and effective choice of therapy, and this method may be clinically applicable.

Animals↗