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Biomedical subjects

K Isono

Publications and source records attributed to K Isono.

At least 55 records · Page 3Linked to original sources

Enhanced effects of monoclonal antibody carboplatin immunoconjugates uptake and anti-tumor effects with angiotensin II and tumor necrosis factor.

The most important factor influencing the use of monoclonal antibody immunoconjugates for cancer treatment is effectiveness of enhancement for tumor targeting. We call attention to the vasoactive agents angiotensin II (ATII) for selective increase in tumor blood flow and cytokine tumor necrosis factor (TNF) to improve the vascular permeability of the tumor. Tumor localization and biodistribution were investigated by nude mice transplanted human colon adenocarcinoma (LS-180) with radiolabeled carboplatin immunoconjugates. Tumor activity 48 h after administration of ATII and TNF was significantly higher than in the control group. However, nonspecific accumulation in normal organs was not observed. In vivo anti-tumor effects in animals with ATII and TNF was significantly stronger than in those given the same dose drug alone or immunoconjugates alone. These results indicate that ATII and TNF could be useful tools for induction of stronger inhibition of tumor growth without systemic toxicity.

Adenocarcinoma↗

Chromosome breakage and cell lethality in human hepatoma cells irradiated with X rays and carbon-ion beams.

Prediction of radiosensitivity would be valuable for heavy-ion radiotherapy. Premature chromosome condensation (PCC) technique has been a potential predictive assay in photon radiotherapy, but has not been investigated for hepatomas receiving heavy ions. Two human hepatoma cell lines, i.e., HLE and HLF, were irradiated with either 290 MeV/u carbon ions or 200 kVp X rays. Cell lethality was assayed by colony formation and compared with the unrejoined fraction of chromatin breaks as measured by PCC technique. Carbon ions at linear energy transfer (LET) of 76 keV/micron produced cell death more effectively than those of 13 keV/micron and X rays. For the cell killing, the relative biological effectiveness (RBE) of 13 and 76 keV/micron carbon ions compared with X rays was 1.10-1.24 and 2.57-2.59, respectively. Mean number of chromosomes in HLE and HLF cells was similar to each other, i.e., 60.48 and 60.28. RBEs for chromatin breaks of 13 and 76 keV/micron carbon ions were 1.30-1.31 and 2.64-2.79, respectively. A strong correlation between unrejoined chromatin breaks and cell killing for human hepatoma cells was observed irrespective of radiation quality. We conclude that PCC provides a potential predictor for the radiosensitivity of individual hepatoma that are treated with photon as well as heavy ion irradiation.

Carbon↗

A putative blue-light receptor from Drosophila melanogaster.

A gene encoding a 62.5 kDa homolog of Drosophila melanogaster photolyase was isolated. Purified recombinant protein contained a flavin adenine dinucleotide chromophore. The recombinant protein did not show photolyase activity for either cyclobutane pyrimidine dimers or 6-4 photoproducts in vitro as well as in vivo in Escherichia coli host cells, suggesting that the protein is not a DNA repair enzyme but a blue-light photoreceptor. Reverse transcription polymerase chain reaction analysis showed that the gene is more expressed in head than in body and that it is more expressed in antennae than in legs, wings and mouth appendages. In a phylogenetic tree of the photolyase family, the Drosophila photolyase homolog is located in a cluster containing 6-4 photolyases and mammalian photolyase homologs, which is only distantly related to the clade of higher plant blue-light photoreceptors. The mammalian photolyase homologs are more closely related to Drosophila 6-4 photolyase than to the Drosophila photolyase homolog, suggesting different roles of the photolyase homologs.

Animals↗

Rotational cine cholangiography: evaluation for use in diagnosing bile duct carcinoma.

OBJECTIVE: We evaluated the usefulness of rotational cine cholangiography in the preoperative diagnosis of bile duct carcinoma. SUBJECTS AND METHODS: Rotational cine cholangiography was performed in both the transverse and cephalad anterior oblique planes in 60 patients with obstructive jaundice. Using strict diagnostic criteria, the capability of this technique to detect the confluence of the right hepatic duct and the left hepatic duct, the right anterior segmental duct and the right posterior segmental duct, and the left medial segmental duct was investigated. The angle at which the confluence was revealed was also investigated. In 26 patients with resected bile duct carcinomas, the preoperative diagnosis of cancer spread obtained using this procedure was compared with the histopathologic findings. RESULTS: Overall detectabilities of the confluences of the right hepatic ducts and left hepatic ducts, the right anterior segmental ducts and right posterior segmental ducts, and the left medial segmental ducts were 97.6%, 87.0%, and 93.1%, respectively. The angles of the confluences of the right hepatic ducts and left hepatic ducts and of the right anterior segmental ducts and right posterior segmental ducts were widely distributed: on the other hand, those of the left medial segmental ducts were distributed mainly from 0 degrees to 20 degrees . The accuracies of diagnosis of cancer invasion were 91.7% in the common hepatic ducts, 100% in the right hepatic ducts, 91.7% in the left hepatic ducts, 100% in the right anterior segmental ducts, 83.3% in the right posterior segmental ducts, and 100% in the left medial segmental ducts. CONCLUSION: Rotational cine cholangiography is reliable not only in detecting the confluence of the bile ducts but also in diagnosing the longitudinal extent of cancer spread along the bile duct wall.

Aged↗

Tissue expression of the S100 protein family-related MRP8 gene in human chorionic villi by in situ hybridization techniques.

The present study examined the tissue-expression of MRP8 in human placenta using a biotinylated DNA-probe for in situ hybridization. During the first and second trimesters high level and synchronous expression of MRP8 was detected in cytotrophoblasts (Langhans' cells), placental-tissue macrophages (Hofbauer cells), fibroblast-like cells, endothelial cells and monocytic lineages in the foetal capillaries. The highest expression was seen in large and oval-shaped cytotrophoblasts and stromal-cell populations at around 8-11 weeks. At term placentas had low level MRP8 expression chiefly in the myelomonocytic lineages in foetal blood vessels. The peripheral monocytes in the maternal space also expressed MRP8 at high levels during the first and second trimesters, which subsequently decreased at term. We suggest three hypotheses based on these results; (1) The initial expression of MRP8 may occur in two cell lineages of extra-embryonic and intra-embryonic origin in the first two trimesters; (2) the cytotrophoblasts, placental-tissue macrophages and fibroblasts may play important roles in the production of placental hormones and the immuno-regulation of foetal acceptance; and (3) MRP8-expression may be synchronously inhibited once the trophoblasts and stromal cell-constituents have differentiated in the chorionic villi.

Antigens, Differentiation↗

Expression of wild-type p53 gene confers increased sensitivity to radiation and chemotherapeutic agents in human esophageal carcinoma cells.

The status of the p53 gene of tumor cells can modify the sensitivity of the tumors to radiation and anti-cancer agents. Human esophageal cancer cells (T.Tn) bearing mutated p53 gene were retrovirally transduced with wild-type p53 gene. The transduced cells (T.Tn/p53) which stably expressed wild-type p53 proliferated at the same rate as parental cells. However, the sensitivity to radiation was significantly improved by the transduction and T.Tn/p53 cells became markedly susceptible to cisplatin and etoposide compared with parental cells. Administration of cisplatin noticeably suppressed the growth of T.Tn/p53 tumors but not T.Tn tumors inoculated in nude mice. Forced expression of wild-type p53 gene thereby can increase the sensitivity to DNA damage in esophageal cells.

Animals↗

[Barrett's esophageal cancer].

Barrett's esophageal cancer is generally considered to be generated through the metaplasia-dysplasia-carcinoma sequence from Barrett's epithelium. We have examined 9 cases of Barrett's esophageal cancer resected in our department, and determined that: 1) The cancer is mainly located in the lower esophagus. 2) Metastases are commonly found in the abdomen and mediastinum in advanced-stage disease. 3) Long-term survival can be expected in patients who undergo radical surgery.

Adult↗

[Detection of serum p53 antibodies in colorectal cancer patients and the clinical significance of postoperative monitoring].

p53 protein overexpression was found to induce the production of antibodies in patient serum and, recently, the easy detection of serum antibodies has been made possible. The aim of this study is to determine the significance of serum p53 antibodies in patients with primary colorectal adenocarcinoma in comparison with their clinicopathological features, and the tumor marker sensitivities of carcinoembryonic antigen (CEA), carcinoma antigen 19-9 (CA19-9) and alpha-fetoprotein (AFP). Thirty-nine of 86 patients (45.3%) were positive for serum p53 antibodies. However, there was no relation with the cancer progression or clinicopathological findings. The sensitivities of CEA, CA19-9 and AFP were 36.0%, 38.4%, and 8.1% respectively, but there was no relation between serum p53 antibodies and these three markers. When the sensitivity of serum p53 antibodies and CEA was evaluated according to clinical stage, the presence of serum p53 antibodies was more significantly associated with stage 0, I and II colorectal cancer than was CEA. Thirty-three patients who showed preoperative positivity for serum p53 antibodies were followed by serial evaluation of circulating antibodies after resection. Negative conversions after resection were significantly higher in the "Cur A" group than in the "Cur B" or "Cur C" groups. Serum p53 antibodies appear to be a useful tumor marker independent of the other markers, especially in the early stage, and are expected to be useful in the development of a method of early diagnosis for mass screening, and as a postoperative monitoring marker for colorectal cancer.

Adult↗

The metabolic pathway of visual pigment chromophore formation in Drosophila melanogaster--all-trans (3S)-3-hydroxyretinal is formed from all-trans retinal via (3R)-3-hydroxyretinal in the dark.

Carotenoid-depleted fruit flies, Drosophila melanogaster, were reared on yeast/glucose medium containing lipid-depleted white corn grits and cholesterol. After rearing for more than a year, the yield of flies remained constant and the content of 3-hydroxyretinal in a head was three logarithmic units less than that of normal flies reared on medium containing yellow corn grits. When all-trans retinal was supplied as the sole source of retinoids, the flies formed and accumulated all-trans 3-hydroxyretinal in the dark. To examine the metabolic pathway to produce (3S)-3-hydroxyretinal in Drosophila, all-trans retinal was supplemented for two hours to carotenoid-depleted flies in the dark, and the subsequent changes in the composition of 3-hydroxyretinal enantiomers were analyzed using a chiral column on HPLC. The results indicated initial formation of (3R)-3-hydroxyretinal followed by isomerization into the 3S enantiomer. In another set of experiments, the membrane fraction was obtained from the head homogenate of retinoid-depleted flies and an in vitro assay of 3-hydroxyretinal formation from retinal was performed. The 3-hydroxyretinal produced was the 3R enantiomer, supporting the result obtained from the in vivo experiment whereby (3S)-3-hydroxyretinal is produced from retinal via (3R)-3-hydroxyretinal. Addition of NADPH enhanced 3-hydroxyretinal formation and the presence of carbon monoxide inhibited it, suggesting that hydroxylation at the C3 position of retinal occurred via the monooxygenase activity of cytochrome P-450.

Animals↗

Atypical adrenoceptor-mediated relaxation of canine pulmonary artery through a cAMP-dependent pathway.

We studied the existence of beta 3-adrenoceptors in canine pulmonary artery smooth muscle under isometric conditions in vitro. A rank order potency of vascular relaxation was isoproterenol > salbutamol > selective beta 3-adrenoceptor agonists, CL 316243 and BRL 37344. A marked desensitization to salbutamol occurred by pretreatment with salbutamol but not with CL 316243. When beta 1-adrenoceptors were blocked, the relaxant responses to salbutamol were competitively antagonized by the beta 2-adrenoceptor antagonist ICI 118551, whereas the response to CL 316243 was not. Cyanopindolol, a non-selective beta-adrenoceptor antagonist, antagonized CL 316243-induced relaxation in a competitive manner with a pA2 of 6.10, and this value was lower than that when salbutamol was used as an agonist (6.69). Intracellular cAMP levels were increased by CL 316243, an effect that was not altered by ICI 118551. Therefore, beta 3-adrenoceptors may be present and functioning in canine pulmonary artery.

Adrenergic beta-Agonists↗

Biological Effects of Heavy Ion Beam on Human Breast Cancers.

BACKGROUND: Radioresistance of the extensive intraductal component (EIC) is amajor limiting factor in breast conserving therapy (BCT). The purpose of the present experiment was to elucidate the biological effects of a carbon beam on human breast cancer cell lines in order to evaluate its clinical benefits in BCT. METHODS: Human breast cancer cell lines, both grown in culture and inoculated into nude mice were subjected to X-ray (200 kV) and heavy ion beam (290 MeV/u carbon beam) irradiation. The relative biological effectiveness (RBE) of the carbon beam and X-ray irradiation was determined at the level of D10 (10% survival dose) on the dose-survival curve. By using a colony forming assay the survival curves of the three cultured cell lines (YMB-I, OUUB-M, CRL-1500) at a linear energy transfer (LET) of 80 keV/µ m were obtained. Cancer established in nude mice was exposed to single-dose and triple-fractionated irradiation at a LET of 50 keV/µm. The growth of tumorsat various doses was observed and the survival curves were determined using thetumor regrowth assay. RESULTS: The RBE of the carbon beam on each cell line ranged from 2.17 to 2.89 (2.59+/-0.37). That of the tumor in nude mice was 1.53 and 2.00 on exposure to single-dose and fractionated irradiation, respectively. CONCLUSION: Human breast cancer cell lines showed high intrinsic sensitivity to a carbon beam and its effects on the tumor were enhanced by fractionated irradiation. It is worthy using carbon beam is applied to use for clinical trials inBCT.

Journal Article↗

A human bronchial epithelial cell line releases arginine vasopressin: involvement of Ca2+ -activated K+ channels.

To determine whether airway epithelium releases arginine vasopressin (AVP) and, if so, what the mechanism of the release is, we studied cultured human bronchial epithelial cell line, 16-HBE cells, in vitro. The cells spontaneously released small but significant amounts of AVP, and this release was dose dependently increased by platelet-activating factor (PAF) or bradykinin (BK). The PAF- and BK-induced AVP release was inhibited by 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate, a phospholipase C inhibitor, and thapsigargin but not by Ca2+ -free solution. Pretreatment with the big conductance Ca2+-activated K+ channel blocker iberiotoxin attenuated the stimulated release of AVP, whereas apamin and glibenclamide were without effect. These results suggest that human bronchial epithelial cells release AVP and that the release may be stimulated by phospholipase C activation, mobilization of Ca2+ from internal stores and the concomitant activation of big conductance Ca2+-activated K+ channels.

Arginine Vasopressin↗

Airway hyperresponsiveness to histamine in mycoplasmal infection: role of histamine N-methyltransferase.

To elucidate the modulatory role of histamine-degrading enzymes in airway constrictor responses in mycoplasmal infection, we studied hamster tracheal segments under isometric conditions in vitro. Nasal inoculation with Mycoplasma pneumoniae potentiated the contractile responses to histamine but not to methacholine. Pretreatment of tissues with the histamine N-methyltransferase inhibitor SKF 91488 abolished the infection-induced potentiation, whereas, the diamine oxidase inhibitor aminoguanidine had no effect. The histamine N-methyltransferase but not diamine oxidase activity in tracheal tissues was decreased in infected animals. These results suggest that M. pneumoniae causes airway hyperresponsiveness to histamine probably through a reduction of endogenous histamine N-methyltransferase activity.

Amine Oxidase (Copper-Containing)↗

Evaluation of a new staging system by the Japanese Research Society for Gastric Cancer.

The feasibility of the new classification of stage grouping by the Japanese Research Society for Gastric Cancer was evaluated. During the 22-year period between January 1975 and December 1996, a total of 1294 patients with primary gastric cancer underwent laparotomy at the Department of Surgery, Chiba University; 1222 had their lesions removed during the gastrectomy and 72 remained nonresected. Cases of direct operative death totaled 17 (1.3%). Five hundred patients (38.6%) died of a relapse of the original cancer and 42 (3.2%) died of other diseases within the followup period. Six patients (0.5%) were lost during the followup. The 5-year cumulative patient survival rates of the seven stages of the new stage grouping were distinctly proportional, and the differences were also statistically significant except between stages IIIb and IVa. The two major revised points in the new stage grouping, new classification of the depth of cancer invasion, and new stage grouping by a mosaic combination of the degree of invasion and lymph node metastasis were thus found to be reasonable based on the actuarial 5-year survival rates of the subgroups in the same stage. The present study also showed that the classification of stage IV still requires further discussion.

Evaluation Studies as Topic↗

The effects of prostaglandin E1 and tyrosine kinase inhibitors on energy status and protein synthetic ability in hepatic ischemia-reperfusion injury.

The effects of prostaglandin E1 (PGE1) and tyrosine kinase inhibitors on hepatic energy status and protein synthesis in ischemic livers were studied using 31P-magnetic resonance spectroscopy in a rat model. The continuous administration of PGE1 significantly increased the beta-adenosine triphosphate/inorganic phosphate (beta-ATP/Pi) ratio and hepatic protein synthesis rate (HPS) after ischemia-reperfusion injury. Microscopic examination showed that the continuous administration of PGE1 inhibited the development of sinusoidal hemorrhage and edema. Thus, it was concluded that PGE1 has a beneficial effect on ischemia-reperfusion injury in the liver. Pretreatment with tyrosine kinase inhibitor also increased the beta-ATP/Pi ratio; however, when tyrosine kinase inhibitor was injected before ischemia, the HPS became significantly reduced. Based on these data, the protective effect of tyrosine kinase inhibitor is unconvincing.

Alprostadil↗

Benign esophageal stricture caused by diffuse severe esophagitis presenting as ascending fibrosis: report of a case.

A 46-year-old Japanese man was referred to our hospital for treatment of an esophageal stricture. Esophageal cancer was suspected after detailed investigations, and a right transthoracic esophagectomy was performed. The resected specimen showed only nonspecific esophagitis with severe fibrous thickening in the submucosa, but no evidence of malignancy. Between 1906 and 1993, only 19 similar cases of benign esophageal strictures with fibrous thickening, excluding congenital and iatrogenic strictures, have been reported in Japan. These lesions occurred in the middle to lower third of the esophagus in 15 of 19 cases (78.9%), and 8 of the 19 patients (42.1%) were aged between 30 and 50 years. The interval between onset and hospital admission was short, being less than 1 year in 8 of the 12 patients for whom this information was available. Our patient demonstrated a disorder resembling the diffuse severe esophagitis described by Roth in 1974.

Biopsy↗

Beneficial effects of renal transplantation on cardiovascular disorders in dialysis patients.

The present study was conducted to evaluate the impact of successful renal transplantation against the cardiovascular risk factors of patients on maintenance dialysis in whom cardiovascular accidents are the most common cause of death. A total of 74 renal transplant patients with grafts that had been functioning well for longer than 6 months after transplantation were examined before and 6-250 months after transplantation. The mean age was 34 years and the duration after transplantation was 104 +/- 66 months. An improvement in anemia from hemoglobin level of 9.0 to 13.6 g/dl and a decrease in mean systolic blood pressure from 157 +/- 24 to 135 +/- 14 mm Hg (P < 0.001) were observed after transplantation. An elevation in RV5 + SV1 levels by 0.6 mV on electrocardiogram (P = 0.042) was seen without any change in the cardiothorathic ratio on chest X-ray. Echocardiographic measurements of six recipients revealed great improvements in the left ventricular systolic dimension and thickness of the posterior wall of the left ventricle. Moreover, the ejection fraction and fractional shortening rose significantly from 59.4% +/- 16.3% to 75% +/- 8.1%, and from 30.6% +/- 9.2% to 44.8% +/- 7.9% (P = 0.017), respectively. These findings clearly show that successful renal transplantation can significantly improve the cardiovascular function of renal patients on maintenance dialysis.

Adolescent↗