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Biomedical subjects

S Adachi

Publications and source records attributed to S Adachi.

At least 217 records · Page 12Linked to original sources

Inductions of oxidative DNA damage and mesothelioma by crocidolite, with special reference to the presence of iron inside and outside of asbestos fiber.

Inductions of oxidative DNA damage (oh8dG) in vitro and peritoneal mesothelioma in rats (F344, female) were compared between crocidolite (CR) and de-ironized crocidolite [DCR, washed by HCl and ethylenediamine tetraacetic acid (EDTA)] to verify the hypothesis that reactive oxygen species contribute to carcinogenesis, focusing on the role of iron present inside or outside of the CR. The yield of oh8dG was 14.6 oh8dG/10(5)dG in CR and 30.2 in DCR under simple incubation with DNA. In the incubation systems added several chemicals and H2O2, DCR induced higher levels of oh8dG than CR. Especially, the addition of Fe2O3 and H2O2 to DCR increased oh8dG in DNA depending on the Fe2O3 concentration, however, this tendency was not observed in the same system of CR. Surprisingly, 7 out of 10 rats died within 2 days after the injection of 10 mg of Fe2O3 following the DCR injection (5 mg/rat), showing necroses of hepatocytes from the surface of each lobe where CR and Fe2O3 particles had been deposited together. There was no death in other groups of rats. One year after the i.p. injection of CR (5 mg/rat, single injection), mesotheliomas were found in all rats administered DCR and Fe2O3 (2 mg/rat, once a week, for 35 weeks), in 4 rats of DCR alone (n = 10), in 5 rats of CR alone (n = 10) and in none of the rats administered Fe2O3 alone (n = 10). Therefore, present results indicate that the induction of oxidative DNA damage changed even when the same type of asbestos was washed by chemical treatment, and Fe2O3 promoted the development of mesothelioma which was induced by DCR.

Animals↗

Complications associated with CDDP intraperitoneal chemotherapy.

As CDDP-ip is known to affect intraperitoneal tumors directly, and reduce CDDP associated adverse reactions, it has been used not only for ovarian cancer but other intraperitoneal tumors. However ip chemotherapy requires catheter placement at the time of laparotomy. We investigated the complications of catheters as an intraperitoneal administration route. The subjects were 84 patients, 39 with temporary catheters and 45 with an implantable port and catheter system. Twenty-seven percent of the temporary catheter patients experienced complications--infection 8%, inflow obstruction 3%, leakage 5%, extrusion 8%, and severe pain 3%. Furthermore, a total of 22% of patients with an implantable port and catheter system experienced complications--inflow obstruction 9%, infection 2%, leakage 4%, and extrusion 7%. Fortunately, no serious complications were observed at our institutions, and the complication incidence seemed lower compared to that of other institutions.

Adolescent↗

In vivo administration of granulocyte colony-stimulating factor promotes neutrophil survival in vitro.

We recently showed that recombinant human granulocyte-colony stimulating factor (rhG-CSF) maintained the viability of human neutrophils in incubation for up to 72 hours. However, it is not known whether rhG-CSF can enhance neutrophil survival in in vivo situations. To clarify this issue, we investigated neutrophil survival in vitro following in vivo injection of rhG-CSF. Neutrophils were obtained from 4 pediatric patients with malignancies and healthy adult volunteers before and after rhG-CSF administration. Neutrophils obtained before rhG-CSF treatment started to undergo apoptosis after 24 h of incubation. In contrast, the survival of neutrophils drawn after rhG-CSF administration increased by approximately 24 h. Concomitantly, the appearance of typical ladder-like DNA fragmentation was delayed. Such an increase in neutrophil survival was inhibited by co-incubation with either H 7 (10 mumol/l) or H 8 (20 mumol/l), which worked as protein kinase C inhibitors. Although our study did not measure neutrophil survival in vivo directly, it provides us with further evidence that rhG-CSF may function to prolong neutrophil life expectancy in vivo.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Induction of apoptosis in childhood acute leukemia by chemotherapeutic agents: failure to detect evidence of apoptosis in vivo.

This study is designed to investigate whether apoptosis occurs in vivo in pediatric patients with acute leukemia during induction therapy. When patients with common acute lymphoblastic leukemia (cALL) and acute myeloblastic leukemia (AML) were treated with prednisolone (60 mg/m2/day, p.o. or i.v.) and etoposide (150 mg/m2/day, i.v.), respectively, the blast cell counts fell to below 30% and 5%, respectively, in 1 week. However, during this cytoreduction phase, neither morphologically apoptotic cells nor fragmentation of DNA derived from peripheral blast cells were detected at any preparations. On the other hand, cALL but not AML cells spontaneously undergo apoptosis following their culture in vitro. The addition of autologous serum instead of fetal calf serum substantially prevented apoptosis from occurring spontaneously in cALL cells. When cALL and AML cells freshly obtained from patients before therapy were treated in vitro with 10 mumol/l prednisolone and 20 micrograms/ml etoposide, respectively, these cells underwent apoptosis within 6 hours, as determined by a morphological and DNA fragmentation assay. These in vivo and in vitro findings suggest that, although anticancer drugs may induce apoptosis in vivo, these apoptotic cells cannot be detected due to their rapid removal from the circulation.

Adolescent↗

Endothelin ETA receptor antagonist blocks cardiac hypertrophy provoked by hemodynamic overload.

BACKGROUND: We have recently shown that angiotensin II-induced hypertrophy of cultured rat cardiomyocytes was partially blocked by an endothelin (ET) receptor antagonist (BQ123) selective for the ETA subtype, suggesting the possible involvement of endogenous ET-1 in the mechanism of cardiac hypertrophy in vitro. In the present study, we studied the in vivo blockade effects of BQ123 on cardiac hypertrophy provoked by left ventricular overload with aortic banding in adult rats. METHODS AND RESULTS: Forty rats were divided into four groups: (1) sham-operated rats without BQ123 administration, (2) rats with aortic banding without BQ123 administration, (3) sham-operated rats with BQ123 administration, and (4) rats with aortic banding with BQ123 administration. BQ123 (250 micrograms/h) was administered continuously by an osmotic pump starting 24 hours before operation. BQ123 blocked increases in the ratio of left ventricular weight to body weight and in the diameter of cardiomyocytes provoked by aortic banding at 1 week, but those blockade actions were no longer observed at 2 weeks. Skeletal alpha-actin and atrial natriuretic peptide (ANP) mRNA in the left ventricle, transcriptional markers for cardiac hypertrophy, significantly increased in the rats with aortic banding at 1 week and 2 weeks. In the rats with BQ123 administration, despite the hemodynamic overload, skeletal alpha-actin and ANP mRNA in the left ventricle remained at the control levels at 1 week; however, those blockade actions were abolished at 2 weeks. Plasma ET-1 levels increased after aortic banding, peaking at 24 hours, then returned to the basal level at 4 days. Prepro-ET-1 mRNA levels in the left ventricle also increased 24 hours after aortic banding, then declined to the basal level at 4 days. CONCLUSIONS: These data suggest that endogenous ET-1 synthesized in the cardiovascular system plays a role in the mechanism of cardiac hypertrophy during the early phase of pressure overload in vivo.

Actins↗

Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes.

We examined whether apoptosis occurs in cardiomyocytes by hypoxia in vitro. Neonatal rat cardiomyocytes and nonmyocytes were cultured in 95% N2-5% CO2 atmosphere to produce hypoxic conditions. DNA fragmentation into integer multiples of the internucleosomal DNA length was observed in cardiomyocytes as early as 12 hours, whereas nonmyocytes did not show fragmentation of DNA up to 72 hours. DNA fragmentation of cardiomyocytes induced by hypoxia was also confirmed by nick-end labeling in situ. Messenger RNA for Fas antigen, a mediator of apoptotic cell death, was expressed in both cardiomyocytes and nonmyocytes as revealed by Northern blotting and in situ hybridization. In hypoxic condition, Fas messenger RNA levels in cardiomyocytes were upregulated by twofold over controls, whereas those of nonmyocytes were downregulated. These results indicate that cardiomyocyte death by hypoxia can occur via apoptosis and that Fas antigen may be associated with the mechanism of this apoptotic process.

Animals↗

ClC family in the kidney.

PCR cloning strategy was used to isolate cDNAs of ClC family members in the kidney. Three new members, named ClC-K1, ClC-K2, ClC-3, have been isolated. Functional expression studies in the Xenopus oocytes confirmed that these are chloride channel proteins. Northern blot and immunohistochemistry showed that ClC-K1 and ClC-K2 are selectively expressed in the kidney, while ClC-3 distributes in a variety of organs such as brain, lung, and kidney. Identification and characterization of new ClC channel proteins will contribute to a better understanding of chloride transport in the kidney.

Animals↗

[The importance of CA125 immunohistochemical staining in patients with ovarian cancer].

UNLABELLED: CA125 has been regarded as a marker for hyperplastic conditions, such as endometriosis or infectious peritonitis. A high serum CA125 level should therefore be carefully evaluated clinically. We measured CA125 levels in sera and ascites as well as the volume of ascites in patients with ovarian cancer, and also performed immunohistochemical staining of their primary tumors for CA125. RESULTS: 1. The tumor positive rate for CA125 was 49% immunohistochemically. 2. In the patients whose tumors were positive for CA125, the serum CA125 level was 3,309 U/ml and the ascitic fluid CA125 level was 23,621 U/ml. In the patients whose tumors were negative for CA125 the serum and ascitic fluid levels of CA125 were 264 U/ml and 1,919 U/ml, respectively. Both serum and ascitic fluid CA125 levels were significantly higher in the CA125-positive tumor group than in the CA125-negative tumor group (t-test: both p < 0.05). 3. In both groups, the serum CA125 level increased with advancing stage. 4. There was a positive correlation between the serum CA125 level and the volume of ascites in both groups. CA125-positive tumor group: Y = 1.02X + 0.38, r = 0.90, r2 = 0.81 (p < 0.0001) CA125-negative tumor group: Y = 0.34X + 1.35, r = 0.51, r2 = 0.26 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Left ventricular-right atrial shunt with bacterial and rheumatic endocarditis of tricuspid valve].

A 14-year-old boy who was operated on for left ventricular-right atrial shunt with bacterial and rheumatic endocarditis of the tricuspid valve (TV) is reported. The patient was pointed out perimembranous ventricular septal defect (VSD) at 4-month old and had complaint of occasional high fever for a half year. The echocardiography showed a vegetation at the TV. The vegetation did not disappear despite of administration of antibiotics for 2 weeks, and pulmonary embolism occurred. Then, the patient underwent resection of the vegetation and direct closure of VSD. The left ventricular-right atrial shunt was formed by the direct communication between VSD below TV annulus and the perforation of septal leaflet of TV adhered to the ventricular septum due to bacterial and rheumatic endocarditis. Earlier operation is needed for this type of case because antibiotics is not effective for the valvular disease.

Adolescent↗

[Clinical results of UFT against ovarian carcinoma].

We carried out a phase II study on single oral administration of UFT in 17 patients with ovarian carcinoma. Two PR cases were observed out of 13 evaluable cases for a response rate was 15.4%. Side-effects, appearing in 10 of the cases (58.8%) were mainly anorexia (17.6%), stomatitis (17.8%), nausea/vomiting (11.8%), leukopenia (11.8%) and thrombocytopenia (11.8%), but they were not serious. UFT proved useful in the treatment of patients with ovarian carcinoma.

Administration, Oral↗

[Surgical treatment of descending thoracic aortic aneurysm with simple aortic cross-clamping versus left heart bypass using centrifugal pump].

Surgical treatment has been employed in 52 patients (pts) with descending thoracic aortic aneurysm (DS-TAA). Based on the adjuncts during aneurysmal repair, the series is divided into 2 groups; simple aortic cross-clamping was utilized to manage the lesion in group SC (n = 42), while left heart bypass using a centrifugal pump was employed during the period of aortic occlusion in LHB group (n = 10). Of these 52 pts, 4 died in hospital (group SC:2, group LHB:2). The most common complication was the respiratory failure following the renal failure. No paraplegia occurred in both groups. Biochemistric measurements of alanine aminotransferase, creatinine (CRN) and amylase (AMY) showed no difference between group SC and group LHB. In pts of SC group with normal renal function, post-operative maximum (post Max) CRN during the first month had a logarithmic correlation with total aortic cross-clamp time (TAXT). The post Max CRN of LHB group with normal renal function remained less than 3.0 mg/dl even in the case with TAXT over 60 minutes. There is also a linear correlation of post Max AMY in pts of SC group. Late survival at 4 years, including hospital death, were 83% in SC group and 63% in LHB group. We conclude that DS-TAA cases with TAXT of less than 30 min with good distal organ function can be managed with simple aortic cross-clamping; otherwise usage of LHB was recommended to support distal circulation.

Adult↗

Aphidicolin potentiates apoptosis induced by arabinosyl nucleosides in human myeloid leukemia cell lines.

We investigated the effect of aphidicolin, an inhibitor of DNA polymerase alpha and delta, on the induction of apoptosis by arabinosyl nucleosides in a human promyelocytic leukemia cell line, HL-60. Pretreatment of HL-60 cells with aphidicolin (2 microM) significantly increased the number of morphologically apoptotic cells induced by 1-beta-D arabinofuranosylcytosine (ara-C) during 4 hr of incubation. This is consistent with the appearance of DNA fragmentation as determined quantitatively by diphenylamine or by agarose gel electrophoresis. The inhibition of cell growth on day 3 after drug exposure was correlated with the degree of apoptosis: Such synergistic interaction between aphidicolin and ara-C has also been observed in other human myeloid leukemia cell lines, U937 and KG-1. In addition, the induction of apoptosis by 9-beta-D arabinofuranosyladenine or 9-beta-D arabinofuranosylguanine is augmented by aphidicolin.

Aphidicolin↗

Oxidative damage of nuclear DNA in liver of rats exposed to psychological stress.

Male Sprague-Dawley rats were exposed to conditioned emotional stimuli in a communication box, which is much more psychologically conditioned stress than the commonly used restraint and water immersion, to investigate the induction of oxidative DNA damage by psychological stress. Significantly higher levels of 8-hydroxy-2'-deoxyguanosine in rat liver nuclear DNA than in the controls [1.46 +/- 0.19 (SD) 8-hydroxy-2'-deoxyguanosine/10(5) deoxyguanosine] were detected immediately after the second (1.90 +/- 0.27, P < 0.01), third (3.10 +/- 0.94, P < 0.01), and fourth exposure (2.95 +/- 1.17, P < 0.01) to conditioned emotional stimuli. This is the first evidence that oxidative damage to nuclear DNA is induced by psychological stress.

Animals↗

[Clinical utility of computed radiography (CR) for the diagnosis of lung cancer].

To clarify the clinical utility of computed radiography (CR) for the diagnosis of lung cancer, several kinds of image-processed CR images were compared with conventional radiographs (CXR). The images in the three patients with peripheral lung cancer were processed by the following six types: 1) processing close to CXR (plain CR), 2) wide latitude and high frequency emphasis (wide CR), 3) advanced high frequency emphasis (HE-CR), 4) lower frequency emphasis (LE-CR), 5) single exposure dual energy subtraction (ES) and 6) ES with lower frequency emphasis (LE-ES). In the two cases of hilar lung cancer, 1) plain CR, 2) wide CR, 3) CR tomographs similar to CXR tomographs (plain CR-TOMO) and 4) high frequency emphasized CR tomographs (HE-CR-TOMO) were processed. Twenty-six radiologists rated the image-processed CR images using a 5 point rating scale method. The following results were found for the evaluation of lung anatomy: almost all image-processed CR images were equal or superior to CXR; especially scores for plain CR were better than those for CXR in all anatomical structures studied; scores for ES were superior to those for plain CR in the bilateral main bronchi, left upper lobe bronchus and right paratracheal stripe; and scores for CR tomographs were better than those for CXR tomographs. In peripheral lung cancer, plain CR and ES were superior to CXR. Especially ES had the best scores. In hilar lung cancer, plain CR and CR tomographs were judged better than CXR and CXR tomographs. These findings indicate the usefulness of CR images for the diagnosis of lung cancer.

Aged↗