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Biomedical subjects

M Hirota

Publications and source records attributed to M Hirota.

At least 55 records · Page 3Linked to original sources

Enhanced cytotoxicity in a Z-photoisomer of a benzopyran derivative of propolis.

(Z)-2,2-Dimethyl-8-(3-methyl-2-butenyl)-benzopyran-6-propenoic acid (1) was isolated from Brazilian propolis, together with the known benzopyran derivative, (E)-2, 2-dimethyl-8-(3-methyl-2-butenyl)-benzopyran-6-propenoic acid (2). The structure was determined by spectroscopic analyses, which included 1D and 2D (1)H and (13)C NMR experiments, as well as MS, IR, and UV spectroscopy. Compound 2 rapidly changed to 1 under UV irradiation conditions (365 nm), and the reverse reaction was also observed. The ratio of 1 to 2 reached 2.3 when the reaction began from either 1 or 2, indicating a photostationary state. Compound 1 displayed an approximate 7-fold stronger cytotoxicity against human lung carcinoma cells (HLC-2) compared with 2.

Antineoplastic Agents, Phytogenic↗

Novel BCR-ABL transcript containing an intronic sequence insert in a patient with Philadelphia-positive acute lymphoblastic leukaemia.

In a patient with Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL), a novel variant of the chimaeric BCR-ABL mRNA transcript was detected by reverse transcription polymerase chain reaction (RT-PCR). Sequencing revealed the novel transcript to be a chimaeric mRNA produced by fusion of the BCR exon 14 (b3) to the ABL exon a2 with a 49-base pair (bp) insertion of an ABL intron 1b sequence between them. The insertion of the 49 bp introduced a stop codon. These data show that this variant of the chimaeric mRNA would not be translated into the p210 BCR-ABL protein. This could be one of the explanations as to why clinically the patient has responded well to therapy and continues to follow a mild clinical course.

Aged↗

Intraductal papillary tumors of the pancreas. Histopathologic correlation of MR cholangiopancreatography findings.

PURPOSE: To evaluate MR cholangiopancreatography (MRCP) findings of intraductal papillary tumors of the pancreas and correlate them with histopathology. MATERIAL AND METHODS: Seventeen patients with intraductal papillary tumor of the pancreas underwent MRCP before surgery. MRCP findings were correlated to histopathology with regard to the presence of septa and excrescent nodules in the cystic lesion, communication between the cystic lesion and the main pancreatic duct (MPD), degree of dilatation of MPD, and dilatation of the common bile duct (CBD). RESULTS: MRCP demonstrated septa in 17 cases (100%), excrescent nodules in 8 cases (47.1%), communication between the intraductal papillary tumor and the MPD in 14 cases (82.3%), dilatation of MPD over 50% in 6 cases (35.3%), and dilatation of CBD in 3 cases (17.6%). These findings showed excellent correlation with histopathology. The septum on MRCP corresponded with a layer of connective tissue with pancreatic duct epithelium. Excrescent nodules in the carcinomas consisted not only of malignant cells, but also of dysplasia and adenoma. Excrescent nodules in adenomas were consistent not only with minimal papillary growth of adenoma, but also with proliferation of fibrosis, and hematoma and organized fibrin with minimal fibrosis. Pancreatic tissue was affected by chronic pancreatitis in all cases. Cases with dilatation of CBD on MRCP were due to microscopic invasion by the carcinoma. CONCLUSION: MRCP appearances of intraductal papillary tumors are well correlated with the findings at histopathology.

Adenocarcinoma, Papillary↗

Relationship between plasma cytokine concentration and multiple organ failure in patients with acute pancreatitis.

The dynamic aspects of circulating cytokines and cytokine modulators and their relationship with development of multiple organ failure (MOF) in patients with acute pancreatitis were analyzed. All cytokine and C-reactive protein levels in the circulation were higher than those in the MOF group. In particular, plasma concentrations of soluble tumor necrosis factor receptors (sTNF-RI and sTNF-RII) were significantly higher in patients with MOF than in those without even at admission. Furthermore, plasma concentrations of sTNF-Rs and interleukin-1 (IL-1) receptor antagonist (IL-1ra) were much higher than those of their counterparts, TNFalpha and IL-beta, respectively. These results suggest that the plasma concentrations of sTNF-Rs are useful predictors for the development of MOF, and actions of TNF-alpha and IL-1beta could be regulated by their modulators (soluble receptor and receptor antagonist, respectively) in the pathologic condition of severe acute pancreatitis.

Acute Disease↗

The pattern of CPP32/caspase-3 expression reflects the biological behavior of the human pancreatic duct cell tumors.

Caspase-3/CPP32, a member of the Ced-3-family of cysteine proteases, is an important mediator of programmed cell death (apoptosis). Intraductal papillary-mucinous tumor of the pancreas (IPMT) is a unique tumor that grows intraductally with rare stromal invasion. However, it is not possible to distinguish noninvasive from invasive IPMT preoperatively. To examine whether caspase-3 expression reflects the biological behavior of pancreatic tumors, we investigated this enzyme expression by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in 22 pancreatic duct cell carcinomas (PDC) and 13 IPMT cases. Caspase-3 mRNA was overexpressed in PDC and IPMT with carcinoma when compared with normal pancreatic tissue or IPMT with adenoma. The immunoreactivity of this enzyme was predominantly found in the cytoplasm of invasive tumors (PDC and invasive IPMT). There was a significant correlation between the cytoplasmic staining and malignant grade of the tumors. In contrast, the nuclear expression of this enzyme was significantly higher in noninvasive than in invasive tumors (p = 0.0015). Cytoplasmic expression of caspase-3 may be related to the invasiveness of pancreatic tumors. In contrast, nuclear expression of this enzyme may reflect the benign biological behavior of IPMT.

Apoptosis↗

Tumor necrosis factor alpha acts on cultured human vascular endothelial cells to increase the adhesion of pancreatic cancer cells.

We studied the effect of tumor necrosis factor alpha (TNFalpha), one of the major inflammatory cytokines, on the adhesive reaction of pancreatic cancer cells to human umbilical vein endothelial cells (HUVECs) and on the hepatic metastasis of cancer cells in vivo. After TNFalpha stimulation, the expression of E-selectin, an adhesion molecule to neutrophils on HUVECs, increased. In addition, the adhesion of pancreatic cancer cells to HUVECs increased after TNFalpha stimulation, as was observed with neutrophils. The TNFalpha-induced adhesive response depended on the extent of sialyl Lewis(a) expression on cancer cells. The hepatic metastasis in vivo was often observed when cancer cells expressing a high amount of sialyl Lewis(a) were inoculated intrasplenically after increase in plasma TNFalpha concentration by lipopolysaccharide administration. Because sialyl Lewis(a) on cancer cells is a ligand for E-selectin on HUVECs, as sialyl Lewis(x) on neutrophils, TNFalpha upregulated the adhesive interaction between sialyl Lewis(a) on cancer cells and E-selectin on HUVECs. These results suggest that production of TNFalpha after surgical trauma may stimulate the hematogenic metastasis of cancer cells with a high sialyl Lewis(a) expression.

Animals↗

Influence of extracellular K+ concentrations on quinidine-induced K+ current inhibition in rat ventricular myocytes.

Hypokalaemia is one of the important risk factors for development of torsades de pointes. We recently reported that hypokalaemia increased the electrocardiographic QT interval in rats treated with quinidine, but did not alter the arrhythmogenic potency of quinidine. In this study, we have investigated the influence of extracellular potassium concentration ([K+]o) on the inhibition of several types of cardiac potassium currents by quinidine. Such types of currents include the delayed rectifier potassium current (I(K)), the transient outward current (Ito), and the inward rectifier potassium current (I(K1)), as measured in isolated rat ventricular cells using patch-clamp techniques. Concentration-dependent effects of quinidine on I(K), Ito, and I(K1) were evaluated under both normal ([K+]o = 5.4 mM) and hypokalaemic ([K+]o = 3.5 mM) conditions. In contrast to both I(K) and Ito, which were barely influenced by changes in [K+]o, I(K1) was significantly inhibited by hypokalaemia. Furthermore, while quinidine suppressed both I(K) and Ito in a concentration-dependent manner, the inhibitory potency of quinidine on these currents was not influenced by changes in [K+]o. The respective normal and hypokalaemic IC50 values for quinidine were 11.4 and 10.0 microM (I(K)), and 17.6 and 17.3 microM (Ito). Although higher concentrations of quinidine were required to inhibit I(K1), the inhibitory potency of quinidine was also found to be insensitive to changes in [K+]o. Thus, in rats, the inhibitory potency of quinidine for the K+ current-types I(K), Ito and I(K1) is barely influenced by changes in [K+]o. These findings are consistent with our previous report showing that the QT-prolonging potency of quinidine was not altered under hypokalaemic conditions. However, whilst hypokalaemia does not affect I(K) or Ito, it can inhibit I(K1) and can result in QT prolongation in-vivo.

Adrenergic alpha-Antagonists↗

(10E,12Z,15Z)-9-hydroxy-10,12,15-octadecatrienoic acid methyl ester as an anti-inflammatory compound from Ehretia dicksonii.

The methanol extract of Ehretia dicksonii provided (10E, 12Z, 15Z)-9-hydroxy-10,12,15-octadecatrienoic acid methyl ester (1) which was isolated as an anti-inflammatory compound. Compound 1 suppressed 12-Otetradecanoyl-phorbol-13-acetate (TPA)-induced inflammation on mouse ears at a dose of 500 microg (the inhibitory effect (IE) was 43%). Linolenic acid methyl ester did not inhibit this inflammation at the same dose. However, the related compounds of 1, (9Z,11E)-13hydroxy-9,11-octadecadienoic acid (5) and (9Z,llE)13-oxo-9,11-octadecadienoic acid (6), showed potent activity (IE500 microg of 63% and 79%, respectively). Compounds 1, 4 ((9Z, 12Z, 14E)-16-hydroxy-9,12,14-octadecatrienoic acid), 5 and 6 also showed inhibitory activity toward soybean lipoxygenase at a concentration of 10 microg/ml.

Animals↗

Quenching of bacteriochlorophyll fluorescence in chlorosomes from Chloroflexus aurantiacus by exogenous quinones.

The quenching of bacteriochlorophyll (BChl) c fluorescence in chlorosomes isolated from Chloroflexus aurantiacus was examined by the addition of various benzoquinones, naphthoquinones (NQ), and anthraquinones (AQ). Many quinones showed strong quenching in the micromolar or submicromolar range. The number of quinone molecules bound to the chlorosomes was estimated to be as small as one quinone molecule per 50 BChl c molecules. Quinones which exhibit a high quenching effect have sufficient hydrophobicity and one or more hydroxyl groups in the alpha positions of NQ and AQ. Chlorobiumquinone has been suggested to be essential for the endogenous quenching of chlorosome fluorescence in Chlorobium tepidum under oxic conditions. We suggest that the quenching effect of chlorobiumquinone in chlorosomes from Chl. tepidum is related to the 1'-oxo group neighboring the dicarbonyl group.

Bacteriochlorophylls↗

[The comparison of sensitivity between immunostaining and a simplified PCR-cold SSCP method in p53 genomic mutations].

The PCR-SSCP (single strand conformational polymorphism) method has been widely employed to screen mutations in a variety of genes because of its rapidity and simplicity in the operation. Using this method, we have examined mutations of some tumor-related genes including p53 and Ki-ras. In this study, we have evaluated the PCR-Cold (non radioactive) SSCP method for detection of p53 point mutations in comparison with immunohistological detection of p53 and PCR-direct sequencing. The results indicated that the PCR-Cold SSCP method had the same sensitivity with that of PCR-direct sequencing method, and had higher sensitivity than that of immunohistochemical method (IHC).

Genes, p53↗

[SIRS and CARS: discussion based on the pathologic condition of acute pancreatitis].

Relationship between SIRS and CARS in the pathologic condition of acute pancreatitis was discussed. SIRS promotes excessive inflammatory reaction and CARS induces the susceptibility to infection. Both conditions can develop into organ failure in acute pancreatitis. Hence, countermeasures for both conditions are mandatory in the care of patients with acute pancreatitis.

Acute Disease↗

Augmentation of UDP-GalNAc: Fucalpha1-2Gal alpha1-3 N-acetylgalactosaminyl transferase activity in nitrosamine-induced hamster pancreatic cancers.

Pancreatic cancers induced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters produce blood group-A antigen (BG-A Ag), which is not present in the normal pancreas. To understand the neo-expression mechanism of BG-A Ag, we examined uridine diphosphate (UDP)-N-acetylgalactosamine (GalNAc): fucose (Fuc) alpha1-2 galactose (Gal) alpha1-3 GalNAc transferase (alpha1-3 GalNAc Tf) activity, the enzyme responsible for BG-A production. The specific activity of alpha1-3 GalNAc Tf in pancreatic cancers was approximately 8,000 nmole/g protein/h, whereas it was absent from the normal pancreas. Although the antrum and colon express A-Tf and BG-A Ag, the divalent cation requirements of alpha1-3 GalNAc Tf in these tissues were different from those of cancers. These results suggest that alpha1-3 GalNAc Tf is activated during BOP-induced pancreatic carcinogenesis, and that there are multiple alpha1-3 GalNAc Tf isozymes present in hamster tissues.

Animals↗

Inhibitory effect of iron-oxidizing bacteria on ferrous-promoted chalcopyrite leaching

It is generally accepted that iron-oxidizing bacteria, Thiobacillus ferrooxidans, enhance chalcopyrite leaching. However, this article details a case of the bacteria suppressing chalcopyrite leaching. Bacterial leaching experiments were performed with sulfuric acid solutions containing 0 or 0.04 mol/dm3 ferrous sulfate. Without ferrous sulfate, the bacteria enhance copper extraction and oxidation of ferrous ions released from chalcopyrite. However, the bacteria suppressed chalcopyrite leaching when ferrous sulfate was added. This is mainly due to the bacterial consumption of ferrous ions which act as a promoter for chalcopyrite oxidation with dissolved oxygen. Coprecipitation of copper ions with jarosite formed by the bacterial ferrous oxidation also causes the bacterial suppression of copper extraction. Copyright 1999 John Wiley & Sons, Inc.

Journal Article↗

Phosphorylation of nonstructural 5A protein of hepatitis C virus: HCV group-specific hyperphosphorylation.

We previously showed that two proteins with molecular weights of 56 and 58 kDa are produced from nonstructural protein 5A (NS5A) derived from hepatitis C virus (HCV)-1b genotype. The 56-kDa protein is phosphorylated at serine residues in NS5A, including those located in the C-terminal region of NS5A, while the 58-kDa protein, the hyperphosphorylated form of the 56-kDa protein, is phosphorylated at serine residues in the central region. This hyperphosphorylation is dependent on the presence of HCV NS4A protein. To clarify whether NS4A-dependent phosphorylation also occurs in other HCV genotypes, phosphorylation of NS5A was analyzed by two-dimensional gel electrophoresis. Here, we report that NS5A from the HCV-2a genotype was phosphorylated. However, hyperphosphorylation of NS5A occurs in the HCV-1b genotype but not in the -2a genotype. This result suggests that modification of NS5A phosphorylation reflects the virological features of HCV and that there are physiological differences in the roles of differently phosphorylated NS5A between HCV genotypes.

Alkaline Phosphatase↗

Clinical evaluation of transhiatal bilateral splanchnicotomy for patients with intractable supramesenteric pain.

Although a transhiatal bilateral splanchnicotomy (TBS) has many advantages, it has not been widely employed as an effective minimal invasive therapy for intractable supramesenteric pain. Furthermore, the effects of TBS have not yet been clearly evaluated. Between 1995 and 1997, TBS was performed on 11 patients with intractable epigastric and/or flank pain due to unresectable pancreatic cancer, chronic pancreatitis, or an unknown cause. The effect of TBS on the pain was evaluated using a novel simple pain score and pain reduction percentage scaled on the basis of the medication and the judgments by patients themselves, respectively. The detection and cutting of the bilateral great splanchnic nerves were easily performed in all of the patients using common flexible chondrocostal retractors. The evaluation of the TBS effect using the pain score clearly demonstrated the early and late mean postoperative pain score (1.1 +/- 0.9 and 1.4 +/- 1.2: mean +/- SD) to be significantly (P = 0.0002 and P = 0.002, respectively) lower than the preoperative pain score (3.5 +/- 0.7). Furthermore, the mean postoperative pain reduction percentage (85% +/- 13%) evaluated by those patients was also significantly different (P < 0.0001). The present study showed no significant complications for TBS, except for minor complications such as the transient fall of blood pressure and reparable pleural damage. Interestingly, a long-term follow-up revealed that no complications related to the splanchnicotomy were observed. These results indicate that TBS is a useful treatment for patients with intractable supramesenteric pain caused by cancer as well as benign diseases.

Abdominal Pain↗

Pheophytinization of bacteriochlorophyll c and energy transfer in cells of Chlorobium tepidum.

Bacteriochlorophyll (BChl) c in whole cells of Chlorobium tepidum grown at 46 degrees C changed into bacteriopheophytin (BPhe) c within 10 days after reaching full growth. When a small amount of C. tepidum cells in which BChl c had been completely pheophytinized were transferred to a new culture medium, normal growth was observed after a short lag phase, and the absorption spectrum of the growing cells showed the presence of a normal amount of BChl c. During the growth of C. tepidum in the new culture, the BChl c concentration was nearly proportional to the cell density measured by turbidity (OD640). These results indicate that C. tepidum can survive even when BChl c has been completely pheophytinized and that BChl c is newly synthesized in such cells when transferred to a new culture medium. In partly pheophytinized cells, upon excitation of BPhe c at 550 nm the fluorescence emission spectrum showed maxima at 775 and 810 nm, which correspond to emissions from BChl c and BChl a, respectively. This indicates energy transfer from BPhe c to BChl c and BChl a. In cells in which BChl c was completely pheophytinized, fluorescence measurements were indicative of direct energy transfer from BPhe c to baseplate BChl a. These findings suggest that when BChl c in C. tepidum cells is pheophytinized, the product (BPhe c) remains in the chlorosomes and continues to work as a light-harvesting pigment.

Bacteriochlorophylls↗