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Biomedical subjects

K Isono

Publications and source records attributed to K Isono.

At least 145 records · Page 8Linked to original sources
PubMed1996

A feasibility study on L-[1-carbon-11]tyrosine and L-[methyl-carbon-11]methionine to assess liver protein synthesis by PET.

UNLABELLED: We studied the potential of L-[1-11C]tyrosine ([1-11C]Tyr) and L-[methyl-11C]methionine ([Me-11C]Met) as tracers for measuring protein synthesis rate (PSR) in the liver by PET and proposed their metabolic models. METHODS: In the liver and plasma of control and cycloheximide-treated mice injected with [1-14C]Tyr and [Me-3H]Met, incorporation of the radioactivity into the acid-soluble fraction and chloroform/methanol-extract (CM), RNA and protein fractions were measured. Data were compared with those from rat studies with 11C-labeled analogs and PET. RESULTS: In mice, liver uptake of [Me-3H]Met was over twice as large as that of [1-14C]Tyr. Similar uptake patterns of the 11C-labeled analogs were found in rats by PET. In the mouse liver at 1 to 6 hr after injection, approximately 69%-73% of the 14C was detected in the protein fraction, whereas approximately 65%-70% of the 3H was in the CM fraction, which reflected phospholipid synthesis. In plasma, the percentages of the protein fractions were approximately 73%-76% for 14C and approximately 36%-46% for 3H. Gel-filtration analysis suggested that 80% of the 14C-labeled plasma proteins was albumin originating from the liver, which corresponds to approximately 25% of the total labeled proteins synthesized in the liver at 6 hr. When protein synthesis was inhibited by cycloheximide, the liver uptake of the [1-14C]Tyr and the protein-incorporation of 14C in the liver and in plasma were decreased dose-dependently. On the other hand, uptake of [Me-3H]Met was significantly enhanced in the liver due to increased incorporation into the CM fraction. CONCLUSION: [1-Carbon-11]Tyr can be used for measuring the PSR in the liver by PET. Liver uptake of [Me-11C]Met mainly reflects phospholipid synthesis through the transmethylation process.

Animals↗
PubMed1996

[Indications of rethoracotomy after esophagectomy for esophageal cancer].

Indications of rethoracotomy after esophagectomy for esophageal cancer are reviewed in this paper. Hemothorax, pneumothorax, pyothorax and chylothorax are the main causes of rethoracotomy. Complications indicating rethoracotomy are summarized as follows: 1) Hemothorax; emergency rethoracotomy is indicated in cases of bleeding through the chest drain over 100ml/hr, which is continuing over 5 hours or in cases when normal blood pressure cannot be maintained without blood transfusion. In many cases the bleeding point is the chest wall, from the branches of the intercostal artery. 2) Pneumothorax; reoperation for pneumothorax is rare. But rethoracotomy and bullectomy or closure of fustula is indicated when a large volume of air leakage and lung collapse continues over a week. 3) Pyothorax; old pyothorax with bronchial fistula is treated by closure of fistula and plombage with omentum or muscle flap. 4) Chylothorax; chylothorax is not a frequent complication of esophageal surgery but when it occurs reoperation is not rare. In cases with 1,500ml/day or more of chyle drainage for over 5 days under fasting with intravenous hyperalimentation, rethoracotomy and ligation of thoracic duct is indicated.

Chylothorax↗
PubMed1996

[Growth inhibition of human pancreatic cancer by farnesyl transferase inhibitor].

Ras is one of the key components in the signal transduction for cell growth. For acquisition of biological activity, Ras protein is required to bind to the inside of the plasma membrane after post-translational farnesylation. Manumycin, a competitive farnesyl transferase inhibitor, inhibits the growth of human pancreatic cancer cells (SUIT-2, MIAPaCa-2, AsPC-1, BxPC-3) in a dose dependent manner. The inhibitory concentration (IC50) of cell lines with a mutant K-ras gene (SUIT-2, MIAPaCa-2, AsPC-1) was lower than that of BxPC-3 with a wild-type. A high concentration of manumycin induced apoptosis, which is related to the inhibition of cell growth. Inhibition of Ras activity might be a new anti-cancer therapy in pancreatic cancer in which Ras plays a role.

Alkyl and Aryl Transferases↗
PubMed1996

[Assessment of proliferative cell nuclear antigen expression and clinical prognosis in gastric malignant lymphoma].

Clinicopathological study was performed in 15 resected cases of gastric malignant lymphoma. The clinicopathological features were as follows. 1) In 6 of 15 cases, the tumor was located in the upper part of the stomach. 2) Lymph node metastasis was observed in 5 of 12 cases. 3) In 3 of 15 cases, multiple tumorous lesions were noted. We also studied the relationship between PCNA expression and clinical prognosis in 10 cases, specimens of which were well preserved, out of 15 cases. About 500 nuclei immunohistochemically stained by PCNA monoclonal antibody were counted, and results were expressed by positive cell ratio (PCNA labelling index LI%). In conclusion, 1) the positive cases of lymph node metastasis showed a tendency for PCNA LI to increase compared with the negative cases. 2) The recurrent cases showed a tendency for increased PCNA LI compared with the cases without recurrence. 3) Cases with more than 60% of PCNA LI tended to have a poor prognosis compared with those of less than 60%.

Adult↗
PubMed1996

[Organ Preservation].

Organ procurement is the first step of organ preservation. We have developed "in situ machine wash out technique with CMH solution" for the purpose of rapid cooling and complete elimination of blood. The utility of this technique was confirmed by both experimentally and clinically. Two major techniques have been used for organ preservation. One is a simple cold storage. Using this method, it is easy to transport organs for transplantation. In addition, availability of UW solution is another advantage of this method. The other is a continuous hypothermic perfusion. Despite of complexity and difficulty of organ transportation, this technique has some advantages, such as viability assay and pretreatment of organs before transplantation. In our experimental studies, viability assays of canine liver and pancreas were achieved using a organ perfusion machine. We also succeeded to prolong the survival of canine pancreatic allograft by pretreatment of anti-Ia antibody during perfusion. While, cryopreservation is most suitable for cell preservation like pancreatic islets. Recently, gene technology was applied for organ preservation studies. In the future, this might become a potent tool for studies in this field.

Cryopreservation↗
PubMed1995

Computer survey for likely genes in the one megabase contiguous genomic sequence data of Synechocystis sp. strain PCC6803.

Using the computer program GeneMark, the open reading frames (ORFs) previously assigned within the one megabase sequence data of the genome of the cyanobacterium, Synechocystis sp. strain PCC6803 (Kaneko et al., DNA Res. 2: 153-166, 1995), were re-examined. Matrices required by GeneMark for its statistical calculation were generated and modified by running a script termed GeneMark-Genesis that performed recursive application of GeneMark against the Synechocystis data and evaluated the probability scores for optimization. Based on the matrices thus generated, 752 of the 818 previously assigned ORFs (92%) were supported by GeneMark as likely coding sequences, of which 26 were predicted to start at more internal positions than previously assigned. In addition, 50 ORFs were newly identified as likely coding sequences, most of them being shorter than 300 bp. Thus, the procedure was proven to be very powerful to locate likely coding regions within the genomic sequence data of Synechocystis without having prior information concerning their similarity to the genes of other organisms. However, GeneMark did not predict 66 previously assigned ORFs as likely genes: 14 of them showed significant degrees of similarity to known genes and 10 others were found within IS-like elements. It seems that these genes, many of which appear to be exogenous origin, escaped detection by GeneMark as in the case of "class 3 (horizontally transferred) genes" of E. coli, which in turn suggests that genes of different phylogenetic origins might also be detected as such by modifying the matrices.

Base Sequence↗
PubMed1995

mel-18, a Polycomb group-related mammalian gene, encodes a transcriptional negative regulator with tumor suppressive activity.

The mammalian mel-18/bmi-1 gene products share an amino acid sequence and a secondary structure, including a RING-finger motif, with the Drosophila Polycomb group (PcG) gene products Psc and Su(z)2, implying that they represent a gene family with related functions. As Drosophila PcG gene products are thought to function as transcriptional repressors by modifying chromatin structure, Mel-18/Bmi-1 might be expected to have similar activities. Here we have analyzed the function of mel-18 and found that Mel-18 acts as a transcriptional repressor via its target DNA sequence, 5'-GACTNGACT-3'. Interestingly, this binding sequence is found within regulatory or non-coding regions of various genes, including the c-myc, bcl-2 and Hox genes, suggesting diverse functions of mel-18 as the mammalian homolog of the PcG gene. We also demonstrate that mel-18 has tumor suppressor activity, in contrast to bmi-1, which has been defined as a proto-oncogene.

3T3 Cells↗
PubMed1995

Inhibition of specific binding of okadaic acid to protein phosphatase 2A by microcystin-LR, calyculin-A and tautomycin: method of analysis of interactions of tight-binding ligands with target protein.

Several groups have reported that okadaic acid (OA) and some other tight-binding protein phosphatase inhibitors including microcystin-LR (MCLR), calyculin-A and tautomycin prevent each other from binding to protein phosphatase 2A (PP2A). In this paper, we have introduced an improved procedure for examining to what extent the affinity of an enzyme for a labelled tight-binding ligand is reduced by binding of an unlabelled tight-binding, ligand to the enzyme. Using this procedure, we have analysed the dose-dependent reduction of PP2A binding of [24-3H]OA by addition of OA, MCLR, calyculin-A and tautomycin. The results indicate that the binding of the unlabelled inhibitors to the PP2A molecule causes a dramatic (10(6)-10(8)-fold) increase in the dissociation constant associated with the interaction of [24-3H]OA and PP2A. This suggests that OA and the other inhibitors bind to PP2A in a mutually exclusive manner. The protein phosphatase inhibitors may share the same binding site on the PP2A molecule. We have also measured values of the dissociation constant (Ki) for the interaction of these toxins with protein phosphatase 1 (PP1). For MCLR and calyculin-A, the ratio of the Ki value obtained for PP1 to that for PP2A was in the range 4-9, whereas it was 0.01-0.02 for tautomycin. The value of tautomycin is considerably smaller than that (0.4) calculated from previously reported Ki values.

Antifungal Agents↗
PubMed1995

Cloning and characterization of the hrpA gene in the terC region of Escherichia coli that is highly similar to the DEAH family RNA helicase genes of Saccharomyces cerevisiae.

During the course of systematic nucleotide sequence analysis of the terC region of E.coli K-12 by using the ordered lambda phage clones, we found the presence of a gene, termed hrpA, that showed a high degree of sequence similarity to the PRP2, PRP16 and PRP22 genes of Saccharomyces cerevisiae. The products of these yeast genes are known to play their roles in mRNA splicing, and belong to a group of proteins collectively called the DEAH family. The hrpA gene is the first example of a DEAH family gene in prokaryotes. The N-terminal region of the protein it encodes contains conserved sequence stretches characteristic of an RNA helicase. Its molecular mass is calculated to be 146 kDa. Previously, a 135 kDa protein was identified by Moir et al. [J. Bacteriol. (1992) 174, 2102-2110] in this region which is most likely identical to that encoded by hrpA. The C-terminal region of the hrpA gene product seems to contain an RNA binding motif weakly resembling that of ribosomal protein S1 of E.coli. Disruption of the hrpA gene suggested that it is not essential for the growth of E.coli.

Adenosine Triphosphatases↗
PubMed1995

The effect of high-energy shock wave therapy combined with cisplatin on mouse hepatoma.

It is well documented that high-energy shock waves (HESW) can produce antitumor effects in vivo and in vitro. Furthermore, because HESW can be focused on a limited area, this therapy is considered applicable to the treatment of localized cancer. In this study, we investigated the effects of HESW therapy combined with cisplatin (CDDP) on MH134 hepatoma in a mouse model. Tumor growth was inhibited by 1 mg/kg CDDP treatment in combination with 2,000 HESW administration, but not by 1 mg/kg CDDP treatment only. Moreover, the CDDP concentration in the tumor increased after HESW administration. The active oxygen induced by HESW was then investigated by the electron spin resonance system, and it was found that HESW generated hydroxy-radicals. As oxygen radicals have been reported to change cell membrane potential, it is supposed that active oxygen induced by HESW changes cell membrane permeability, and that CDDP is concentrated in the tumor. Therefore, the combined therapy with HESW and CDDP showed synergistic inhibitory effects on tumor growth.

Animals↗
PubMed1995

Tautomycin: an inhibitor of protein phosphatases 1 and 2A but not a tumor promoter on mouse skin and in rat glandular stomach.

Tautomycin isolated from Streptomyces spiroverticillatus is an inhibitor of protein phosphatases 1 and 2A. Tautomycin induced hyperphosphorylation of cytokeratin peptides in human keratinocytes (PHK 16-I cells) 30 times less strongly than did okadaic acid. Repeated applications of tautomycin (30 micrograms, 40 nmol/application) did not induce tumor promotion in a two-stage carcinogenesis experiment on mouse skin initiated with 7,12-dimethylbenz[a]anthracene, whereas okadaic acid (1 microgram, 1.2 nmol/application) as a control induced tumor promotion strongly. As for mucosa of rat glandular stomach, tautomycin induced ornithine decarboxylase 4 h after intubation into the stomach. The tumor-promoting activity of tautomycin was next studied in the glandular stomach initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Administration of tautomycin in the diet (1 mg rat-1 day-1), from week 9 to week 52 of the experiment, inhibited rather than enhanced tumor development in the glandular stomach initiated with MNNG. The percentages of tumor-bearing rats of the groups treated with MNNG plus tautomycin, MNNG alone, and tautomycin alone were 20.0%, 40.6%, and 0% respectively in week 52. The reason for the absence of tumor-promoting activity of tautomycin was studied in relation to tumor necrosis factor alpha (TNF alpha), an endogenous tumor promoter. We found that tautomycin neither enhanced TNF alpha mRNA expression in mouse skin nor induced TNF alpha release in a human stomach cancer cell line (KATO III cells), whereas okadaic acid did both. These results indicate that not all inhibitors of protein phosphatases are tumor promoters, and suggest that tumor promotion of the okadaic acid class of compounds is mediated by TNF alpha.

Animals↗
PubMed1995

Endoscopic ultrasound-guided pancreatography: a case report.

Endoscopic ultrasound-guided pancreatography was performed on a 48-year-old man with a diagnosis of pancreatic stone. A pylorus-preserving pancreaticoduodenectomy had been performed previously on this patient, approximately two years earlier, following the diagnosis of a tumor-forming pancreatitis. Endoscopic retrograde pancreatography and conventional ultrasound-guided percutaneous pancreatography had failed to yield a diagnosis. However, endoscopic ultrasound-guided pancreatography was performed successfully, delineating the pancreatic duct and a filling defect caused by intraductal calculi. Endoscopic ultrasound-guided pancreatography will be a potential alternative in cases when endoscopic retrograde pancreatography has failed or proved non-diagnostic.

Calculi↗
PubMed1995

Rare association of human papillomavirus DNA with esophageal cancer in Japan.

To examine whether human papillomavirus (HPV) DNA is associated with esophageal cancer, frozen and paraffin-embedded neoplasms of the upper aerodigestive tract, including esophageal cancer, were investigated. DNA obtained from frozen specimens and cell lines were analyzed by both polymerase chain reaction (PCR) and Southern blot hybridization. DNA from paraffin-embedded samples were analyzed strictly by PCR. DNA of HPV types 6 and 11 was detected in papillomas of the upper respiratory tract at > 50%. However, HPV DNA was infrequently detected in specimens from the upper digestive tract (31 esophageal cancers and 2 esophageal carcinoma--derived cell lines), even by PCR at a sensitivity of 0.1 copy number per cell. These results suggest that the etiologic significance of HPV infection in esophageal cancer is negligible.

Base Sequence↗
PubMed1995

Enhancement of the antitumor effect by combined use of high-energy shock waves and ATX-70.

The antitumor effects of high-energy shock waves (HESW) in combination with ATX-70 [a gallium-porphyrin complex, 2,4-bis(1-decyloxyethyl)-Ga(III)-1,3,5,8-tetramethylporphyrin++ +-6, 7-dipropionyl diaspartic acid [sequence: see text] were investigated. In vitro, the cell damage to mouse MH134 hepatoma after HESW treatment was enhanced by adding ATX-70. In vivo, HESW and ATX-70 combination therapy inhibited cell growth. However, neither HESW treatment alone nor ATX-70 treatment alone inhibited cell growth. These results imply that the antitumor effects of HESW and ATX-70 combined therapy are caused by activation of ATX-70 by HESW.

Animals↗