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Biomedical subjects

O Katoh

Publications and source records attributed to O Katoh.

At least 37 records · Page 2Linked to original sources

Gastric tumor induction by 1,2-dimethylhydrazine in Wistar rats with intestinal metaplasia caused by X-irradiation.

Five-week-old male Wistar rats were X-irradiated with a total of 20 Gy in 2 equal fractions at a 3-day interval. 1,2-Dimethylhydrazine (DMH) solution was injected i.m. into the back musculature at a dose of 20 mg/kg body weight weekly for 10 weeks, beginning 20 weeks after the final irradiation. Twelve months after the initial carcinogen treatment, tumors in the fundus of the glandular stomach were observed in 5 of 23 animals receiving both X-irradiation and DMH treatment. No tumors of the glandular stomach were observed in the DMH and X-ray alone or nontreatment groups. It is concluded that the presence of intestinal metaplasia may increase sensitivity to the induction of gastric tumors by carcinogens like DMH.

1,2-Dimethylhydrazine↗

[A case of synchronous bilateral double primary lung cancer successfully treated by Nd-YAG laser therapy and chemotherapy].

A 61-year-old man was admitted to our hospital with the chief complaint of hemosputum. He was a heavy smoker. A chest radiograph revealed a tumor shadow in right S3 which invaded the pulmonary artery. There was also an associated patchy shadow in the periphery as well as ipsilateral pleural effusion. Bronchoscopy revealed a near occlusion with superficial infiltration at the right B3 bronchus and a nodular tumor at the bifurcation between the left upper and lingual division bronchi, which was consistent with endoscopic early lung cancer. Although both tumors were histologically diagnosed as squamous cell carcinoma, this was considered to be a case of synchronous double primary lung cancer due to their mutual isolation. The left tumor was subsequently diagnosed as carcinoma in situ. Following Nd-YAG laser therapy for carcinoma in situ and 4 courses of systemic chemotherapy using TXT and CDDP, bronchoscopy revealed no residual cancerous tissue and no tumor apart from the nodular shadow in right S3 was seen on a radiograph. Subsequent right upper and middle lobectomy and lymph node (R2a) dissection revealed no residual tumors.

Antineoplastic Combined Chemotherapy Protocols↗

Human AIM-1: cDNA cloning and reduced expression during endomitosis in megakaryocyte-lineage cells.

The rat AIM-1 gene encoding an Aurora- and Ipl1-like midbody-associated protein serine/threonine kinase has a mitotic regulator function playing a key role in the onset of cytokinesis during mitosis. This report presents a cDNA sequence and megakaryocytic differentiation-dependent expression profile of the human AIM-1 gene. The nucleotide sequences of the human AIM-1 were identified from cDNAs of three cell lines, including cervical carcinoma HeLa cells, colorectal tumor SW480 cells, and normal human diploid skin fibroblast NHDF cells, and no mutation was found. The expression levels of AIM-1 transcript were markedly reduced during differentiation into megakaryocytic cell lineage in human leukemia cells induced by 12-o-tetradecanoyl-phorbol-13-acetate (TPA), suggesting that the downregulation of AIM-1 contributes to the differentiation by repeated duplication of DNA without cytokinesis (endomitosis).

Amino Acid Sequence↗

Vascular endothelial growth factor inhibits apoptotic death in hematopoietic cells after exposure to chemotherapeutic drugs by inducing MCL1 acting as an antiapoptotic factor.

We reported previously that vascular endothelial growth factor (VEGF) inhibits the apoptotic death of hematopoietic cells that is induced by exposure to ionizing radiation (O. Katoh et al., Cancer Res., 55: 5687-5692, 1995). In this study, we show that VEGF also inhibits apoptotic cell death that is induced by exposure to the chemotherapeutic drugs etoposide and doxorubicin. To elucidate the molecular mechanisms underlying this inhibitory effect of VEGF, we examined expression levels of BCL2 family proteins in CMK86, a human leukemia cell line, after treatment with VEGF. Northern blotting and immunoblotting analyses revealed that the expression level of MCL1, a member of the BCL2 family, was increased by VEGF. Moreover, to examine the effects of MCL1 on apoptotic cell death induced by exposure to etoposide, we generated a clonal U937 myeloid leukemia cell line transfected with vectors that promoted the constitutive expression of MCL1. MCL1 decreased the caspase 3 activity induced by exposure to etoposide and increased the viability of the transfected cells after etoposide exposure. Therefore, MCL1 may be involved in the inhibitory effect of VEGF on apoptotic cell death.

Antineoplastic Agents↗

The Krüppel-type zinc finger family gene, HKR1, is induced in lung cancer by exposure to platinum drugs.

To investigate the molecular mechanism associated with the signaling pathway of platinum drug administration, we focused on the C2H2-type zinc finger (ZNF) transcription factor gene family. Here we show cloning of a Krüppel-type ZNF gene, HKR1, which contains Krüppel-associated box (KRAB) domain and ZNF motifs. We found that mRNA expression of the HKR1 gene was induced in lung-cancer cell lines by exposure to cisplatin using Northern blot analysis. Moreover, we also found that HKR1 mRNA expression levels in lung cancers were higher than those in normal lung tissues, and that high expression levels in lung cancers were associated with antemortem platinum drug administration. These results suggest that HKR1 may be associated with the regulation of a signaling pathway involved in the progression of lung cancer or the acquisition of resistance to platinum drugs.

Adenocarcinoma↗

ZK1, a novel Krüppel-type zinc finger gene, is induced following exposure to ionizing radiation and enhances apoptotic cell death on hematopoietic cells.

To identify and early response factor by exposure to ionizing radiation, we cloned the cDNA of a novel Krüppel-type zinc finger (ZNF) gene, ZK1, from a cDNA library constructed from the human leukemia cell line, CMK86, using degenerate primers. This cDNA encoded a protein of 671 amino acids with an A box of Krüppel-associated box (KRAB) domain at the N-terminus, followed by 15 ZNF motifs. The expression level of the ZK1 mRNA in human leukemia cells lines, CMK86 and U937, was increased after exposure to ionizing radiation. Furthermore, murine myeloid precursor 32D cells that were stably transfected with ZK1 cDNA had higher sensitivity to ionizing radiation than the 32D parent cells. These data suggest that the ZK1 gene is one of early response genes by exposure to ionizing radiation, and may have some functions on radiation-induced apoptotic cell death on hematopoietic cells.

Amino Acid Sequence↗

Comparison of quantitative coronary angiographic results after directional coronary atherectomy and balloon angioplasty of protected left main coronary stenosis.

We compared the angiographic and clinical outcomes after directional coronary atherectomy (DCA, 13 patients) with those after conventional balloon angioplasty (BA, 21 patients) in patients with protected left main coronary artery stenosis. The initial success rate was 100% in the DCA group and 81% (17 of 21) in the BA group. Restenosis was present in 2 of 11 patients in the DCA group and 9 of 16 patients in the BA group (18% vs. 56%, P < 0.05). DCA and BA improved a minimal lumen diameter. The initial gain after DCA was greater than that after BA. At follow-up, the minimal lumen diameter was larger and the percentage diameter stenosis was smaller in the DCA group than in the BA group. The late loss and loss index were equivalent in both groups. Compared with conventional BA, DCA in protected left main coronary artery stenosis is associated with a higher angiographic success rate and provides a wider luminal diameter with reduced incidence of restenosis.

Angioplasty, Balloon↗

Impact of cilostazol on intimal proliferation after directional coronary atherectomy.

Cilostazol, a novel platelet aggregation inhibitor, inhibits intimal proliferation in animal models. We randomly assigned 41 patients with lesions suitable for directional coronary atherectomy to the cilostazol group (200 mg/day) or the aspirin (250 mg/day) group. Medication was started before directional coronary atherectomy and was continued to a 6-month follow-up. Serial quantitative coronary angiography and intravascular ultrasound study were performed. Baseline characteristics were not different between the two groups. However, the minimal lumen diameter at follow-up was larger (2.33 +/- 0.60 mm vs 1.81 +/- 0.68 mm, p = 0.016) and the percent diameter stenosis (24.5% +/- 16.6% vs 40.9% +/- 21.0%, p = 0.010) was smaller in the cilostazol group. The change in vessel area was not different, but the percent plaque area at follow-up was smaller in the cilostazol group (55.7% +/- 11.2% vs 64.5% +/- 14.5%, p = 0.044). The restenosis rate was significantly lower in the cilostazol group (0% vs 26%, p = 0.020). We conclude that cilostazol appears to have an inhibitory effect on intimal proliferation after directional coronary atherectomy and may reduce restenosis.

Aged↗

Expression of gamma-glutamylcysteine synthetase (gamma-GCS) and multidrug resistance-associated protein (MRP), but not human canalicular multispecific organic anion transporter (cMOAT), genes correlates with exposure of human lung cancers to platinum drugs.

We examined the steady-state levels of mRNA for gamma-glutamylcysteine synthetase (gamma-GCS), multidrug resistance-associated protein (MRP) and human canalicular multispecific organic anion transporter (cMOAT) in human lung cancer specimens to elucidate their roles in relation to platinum drug resistance in vivo. Seventy-six autopsy samples (38 primary tumours and their corresponding normal lung tissues) obtained from 38 patients were analysed using the quantitative reverse transcription polymerase chain reaction (RT-PCR) method. Both subunits (heavy and light subunits) of gamma-GCS expression levels of normal lung and tumour tissues exposed to platinum drugs during life were significantly higher than those of non-exposed tissues, whereas only the MRP expression levels of tumours were elevated in association with ante-mortem platinum drug exposure. The gamma-GCS and MRP expression levels correlated significantly. The cMOAT expression levels did not correlate with ante-mortem platinum drug exposure. Next, we monitored gamma-GCS heavy subunit expression levels in peripheral mononuclear cells of eight previously untreated lung cancer patients after platinum drug administration, which revealed that these drugs induced gamma-GCS expression in vivo. These results suggest that gamma-GCS expression is induced by platinum drugs in vivo and/or the physiological stress response to xenobiotics.

ATP-Binding Cassette Transporters↗

Effects of miso and NaCl on the development of colonic aberrant crypt foci induced by azoxymethane in F344 rats.

The present study was designed to investigate the effects of dietary miso and NaCl supplementation on the development of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in male F344 rats. A total of 76 rats, six weeks of age, were divided into seven groups and given weekly subcutaneous injections of AOM (15 mg/kg body wt) for three weeks to induce ACF. The animals were placed on diets one week before the first AOM dosing. Group 1 was fed a normal diet as a control. Groups 2-4 were fed diets containing 5%, 10%, and 20% miso, respectively, and Groups 5 and 6 were fed diets containing 2.2% and 4.4% NaCl, respectively, for five weeks. Group 7 was fed a normal diet without carcinogen exposure. Dietary miso inhibited the development of ACF in a dose-dependent manner (y = -3.9x + 140, r = -0.94). Thus the mean numbers of ACF per colon were significantly lower in Groups 3 and 4 than in Group 1 (p < 0.01), and there were fewer aberrant crypts per colon in Group 4 than in Group 1. NaCl supplementation was associated with fewer ACF, but this was not statistically significant. 5-Bromo-2'-deoxyuridine labeling indexes in the colonic epithelium were significantly lower in Group 3 than in Group 1 (p < 0.05). The present results indicate that dietary miso could act as a chemopreventive agent for colon carcinogenesis.

Animals↗

Developmental malformations and intrauterine deaths in gamma-ray-irradiated scid mouse embryos.

PURPOSE: To examine the induction by radiation of developmental malformations and intrauterine deaths in severe combined immunodeficiency (scid) mice. MATERIALS AND METHODS: The scid embryos, as well as those of C.B-17 control mice, were irradiated with graded doses of 60Co gamma-rays on gestation day 8. RESULTS: Intrauterine deaths in scid mice increased with radiation dose, and their frequency was substantially higher than in C.B-17 mice. The LD50 for intrauterine death in scid mice was 0.58 Gy and 1.25 Gy in C.B-17 mice. In addition, after irradiation scid mice showed several types of developmental malformations, including meningoencephalocele, spina bifida, eye defects, tail defects and oedema. Malformation incidences were higher in scid than in C.B-17 mice: 33.3% in scid mice irradiated with 0.75 Gy and 13.0% in C.B-17 mice irradiated with 1.0 Gy. However, when malformation incidences were plotted against intrauterine deaths, all the data, irrespective of the type of mouse, essentially fell along a single straight line. CONCLUSIONS: These results suggest that some mechanism common to both scid and normal mice induces developmental malformations. This mechanism involves cell killing. Residual DNA damage, such as double-strand breaks, could be associated with radiation-induced teratogenesis.

Abnormalities, Radiation-Induced↗

Percutaneous revascularization of lesions with saphenous vein graft failure: influence of chronic total occlusion on early outcome.

The purpose of this study was to evaluate a therapeutic strategy of percutaneous transluminal coronary angioplasty (PTCA) in patients with recurrent angina following coronary artery bypass grafting. The study looked at 112 branches associated with graft failure, excluding new lesions in the native coronary artery (NCA). Chronic total occlusion (CTO) was observed in 50% of NCA (56/112) and in 68% of the grafts (76/112). Thirty-three branches (29%) showed CTO in both NCA and the graft. The overall success rate was 86% (96/112). The success rate on NCA was 98% (44/45) in non-CTO, while in CTO it was significantly lower at 62% (18/29). As to grafts, the success rate was 94% (32/34) in non-CTO, while it was 50% (2/4) in CTO. These characteristics, with respect to lesion morphology and the prevalence of CTO, exerted an influence on the selection of the access vessels for revascularization. Early outcome depended on the result of treatment of CTO.

Acute Kidney Injury↗

Comparison of tumorigenesis between accelerated heavy ion and X-ray in B6C3F1 mice.

The effects of heavy ion and X-ray irradiation on tumorigenesis in B6C3F1 mice were compared. Six-week-old animals were divided into 6 groups and exposed to 0.426 Gy heavy ion irradiation of 290 MeV/u carbon-ion beam (LET 60-210 KeV/micron) at the dose rate of 0.4 +/- 0.2 Gy/min; 0.5 Gy of X-ray irradiation at 0.1 Gy/min or 5 Gy of X-ray irradiation at 1 Gy/min. The mice were killed and an autopsy performed 13.5 months after the whole body irradiation. Body weights were heaviest for both sexes in the 0.5 Gy group and lightest in the 5 Gy one. Total tumor incidences in the males were 30, 56 and 13% respectively in the heavy ion, 5 Gy and 0.5 Gy X-irradiated groups, stomach tumors, lymphomas and adrenal tumors being the most common outcome of the high dose X-rays. Liver tumor induction did not differ significantly among the groups. In the females tumorigenicity was significantly lower for heavy ion than for 0.5 Gy and 5 Gy X-ray irradiation (P < 0.05), the respective incidences, mainly ovary one, being 73%, 17% and 41%. Non-cancerous lesions, such as graying of the hair, glomerular sclerosis and amyloidosis appeared in the 5 Gy group. These findings indicate that 0.426 Gy of heavy ion irradiation induced lower carcinogenicity than 5 Gy of X-irradiation and higher carcinogenicity than that of 0.5 Gy X-irradiation in male mice.

Animals↗

[Legionella pneumonia caused by aspiration of hot spring water after sarin exposure].

A 72-year-old man was exposed to the sarin gas attack in a Tokyo subway on March 20 th, 1995. After exposure, he noticed eye discomfort, chest tightness, headache and weakness of the lower limbs and oropharyngeal muscles. Despite these symptoms, he visited a hot spring on the same day with his family. On March 25 th, his muscle weakness progressed, and a low grade fever appeared. His muscle weakness disappeared 8 days after exposure to sarin, but respiratory failure rapidly developed, necessitating artificial ventilation within four day after hospitalization on March 28th. Chemotherapy with erythromycin, imipenem/cilastatin, and steroid pulse therapy was begu. PCR and culture of sputum collected by bronchofiberscopy were positive for Legionella pneumophila, serogroup I. His respiratory state improved, but subsequent infection with Pseudomonous aeruginosa. Enterobacter cloacae, and Candida tropicalis/glabrata caused his death 71 days after admission. Oropharyngeal muscle weakness caused by sarin-mediated cholinesterase inhibition was strongly suspected as the cause of hot spring water aspiration. Transbronchial lung biopsy revealed organizing pneumonia with fibrosis. Bronchoscopic findings included redness, edema and fragility of all visible areas of the airway, which was thought to be due to bronchitis caused by Legionellosis.

Aged↗

New double wire technique to stent ostial lesions.

We describe a new fast technique to precisely deploy J&J Stents in ostial lesions using two guide wires. The second guide wire is inserted through the proximal stent strut and simultaneously advanced together with the stent on the balloon serving as a position marker that guides stent placement. This technique has been applied in 10 cases with 100% success and with no major complications.

Angioplasty, Balloon↗

A novel point mutation in the steroid sulfatase gene in X-linked ichthyosis.

We analyzed the steroid sulfatase (STS) gene in nine Japanese patients with X-linked ichthyosis (XLI) by a polymerase chain reaction technique and subsequent DNA sequencing. Eight of nine patients showed complete deletion of the STS gene. In a patient of XLI exhibiting a normal amplifying pattern with predicted sizes of the STS gene, a novel mutation was found resulting in the appearance of a stop codon in exon 7 of the STS gene. This suggests that exon 7 or an area in its downstream region is important for STS activity.

Arylsulfatases↗

The role of glucuronidation in 7-ethyl-10-hydroxycamptothecin resistance in vitro.

Although glucuronidation catalyzed by uridine 5'-diphosphoglucuronosyltransferase (UGT) is a major pathway of drug inactivation in humans, glucuronidation in malignant cells has received little attention as a cause of anti-cancer drug resistance. In this study, we tried to elucidate the role of SN-38 glucuronidation in the CPT-11-resistant human lung cancer cell line PC-7/CPT. PC-7/CPT cells possessed an increased activity to glucuronidate SN-38 compared to the parent cells, PC-7. Furthermore, sensitivity of PC-7/CPT cells to SN-38 was improved by inhibiting UGT activity. Western and northern blot analyses demonstrated that this increased activity was due to increased levels of UGT protein and mRNA. These results not only imply that upregulation of UGT activity in PC-7/CPT cells may contribute in part to SN-38 resistance, but also illustrate the important of drug metabolism within malignant cells themselves, as a cause of drug resistance.

Antineoplastic Agents, Phytogenic↗

A case of arrhythmogenic right ventricular dysplasia with left and right ventricular hypofunction in an elderly subject--long-term follow-up.

A 72-year-old man was admitted with palpitations caused by sustained ventricular tachycardia. He had been followed for 27 years, with admissions on 7 occasions, on account of ventricular tachycardias, atrial fibrillation, and congestive heart failure. Electrophysiologic examination detected 2 points of origin of ventricular tachycardia in the right and left ventricles. During the examination a myocardial infarction led to death. At autopsy, most areas of the right ventricle and the left ventricular apex were found to have been replaced by fatty tissue, pointing to severe fatty infiltration into the myocardium. Thus, this patient represented a unique cause of arrhythmogenic right ventricular dysplasia (ARVD) with severe fatty degeneration causing progression of ARVD. It is important that a diagnosis of ARVD is made carefully and rigorously in elderly subjects.

Aged↗