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Biomedical subjects

M Ochiai

Publications and source records attributed to M Ochiai.

At least 127 records · Page 7Linked to original sources

Detection of guanine-C8-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine adduct as a single spot on thin-layer chromatography by modification of the 32P-postlabeling method.

N-(Deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-PhIP) has been shown to be a major adduct in DNA of rats given [3H]PhIP. However, when DNA from organs of rats fed PhIP was analyzed by the 32P-postlabeling method under standard and adduct-intensification conditions, four adduct spots were observed, and 3',5'-pdGp-C8-PhIP was detected as a minor, not a major, adduct spot. Since the three other major adduct spots were suspected to be those of adducted di- or oligo-nucleotides, the 32P-labeled samples were further treated with nuclease P1 and phosphodiesterase I and found to yield only a single adduct spot. The material in this adduct spot was confirmed to be 5'-pdG-C8-PhIP. Thus, using this newly modified 32P-postlabeling method, dG-C8-PhIP was detected as a major adduct in DNA of rats given PhIP.

Animals↗

Gastric carcinoma, an endoscopically curable disease.

Following refinement of endoscopic diagnosis of gastric cancer, the concept of 'early gastric carcinoma' and its endoscopic features have become established. After the wide acceptance of the techniques of endoscopic mucosal resection (EMR), laser therapy and accurate endoscopic-endosonographic assessment of the depth of invasion, curative endoscopic treatment of intramucosal gastric carcinoma has become established. On the basis of the analysis of lymphatic metastasis, the indications for endoscopic treatment of gastric carcinoma have been defined as (1) well-differentiated, intramucosal adenocarcinoma of a superficial elevated lesion (diameter < 2 cm), and (2) well-differentiated, intramucosal adenocarcinoma of a superficial depressed lesion (diameter < 1 cm) having no ulcer or scar inside. The preferred procedure of endoscopic treatment is EMR with careful histological examination of the resected specimen. It is supplemented by repeat EMR, laser therapy, or surgical gastrectomy in case of incomplete resection. For detection of residual cancer and recurrence, periodic endoscopic follow-up is necessary. Early gastric carcinoma is endoscopically curable.

Adenocarcinoma↗

[Clinical effect of arbekacin on MRSA infections after gastrointestinal surgery].

From January 1991 to July 1993, 58 patients with MRSA infections in our clinic at Wakayama Medical College and six affiliated hospitals were administered with arbekacin (ABK). The clinical results were as follows: 1. The clinical efficacy rates of ABK were 84% in pneumonia, 100% in both wound infections and hepatobiliary tract infections, and 85% in total. The bacteriological efficacy rate was 83%. 2. Regarding the administration route, the clinical efficacy rates were 60-79% by the intravenous treatment and inhalation therapy. Especially by the local administration with ABK, MRSA was eradicated in all cases. 3. The sufficient efficacy was obtained by the treatment of ABK alone (89%) and by the combined treatment with ABK (82%) and another antibiotics. From these results, it is concluded that ABK is useful for the treatment of MRSA infections after gastrointestinal surgery.

Administration, Inhalation↗

[A juvenile onset case of moyamoya disease with intraventricular hemorrhage during pregnancy: case report].

We report a primipara with intracranial bleeding during pregnancy. The patient, a 23-year-old female, had history of cerebral ischemic attack during childhood and was diagnosed as having moyamoya disease at the age of ten. She did not undergo reconstructive vascular surgery but had not suffered from the cerebral ischemic attack in the last ten years. She suddenly lost consciousness in the eighth month of pregnancy and was admitted to our hospital. The brain CT scan revealed right paraventricular hemorrhage with ventricular perforation. After the newborn baby was delivered by cesarean section under spinal anesthesia, an emergency ventricle drainage was performed. The angiography demonstrated the occlusion of the internal carotid arteries at C1 portion with evidence of a moderate basal moyamoya network on both sides. Marked dilatation of the posterior lateral choroidal arteries was also seen on both sides, but no aneurysms were found. We supposed that the source of intracranial hemorrhage was a breakdown of the dilated perforating moyamoya vessels that formed the basal collateral network. We also supposed that the time of onset of intracranial hemorrhage might be related to the hemodynamic and hormonal changes occurring during pregnancy. Appropriate counterplans to pregnancy should be made by females with moyamoya disease, because pregnancy may be risky for them.

Adult↗

[Evaluation of myocardial perfusion and ventricular shape in hypertrophic cardiomyopathy using 99mTc-tetrofosmin scintigraphy: comparison with 201Tl myocardial scintigraphy].

Hypertrophic cardiomyopathy (HCM) is known to have the impairment of myocardial perfusion as well as irregularly hypertrophic myocardium. To evaluate myocardial perfusion and ventricular shape in HCM, 99mTc-Tetrofosmin scintigraphy was performed after exercise (Ex) and at resting state (Re) in 10 patients with HCM and was compared with early image (Ea) and delayed image (De) of 201Tl scintigraphy performed after exercise. SPECT images of both 99mTc-Tetrofosmin and 201Tl scintigraphy were analyzed with five scaled visual scores set in 18 segments. The complete concordance ratio between 99mTc-Tetrofosmin (Ex and Re) and 201Tl (Ea and De) images in segmental analysis was 75%. Image quality of 99mTc-Tetrofosmin was seemed to be superior to that of 201Tl scintigraphy. In 9 patients with HCM, 99mTc-Tetrofosmin scintigraphy was performed under the ECG gating and the thickness of septal and free wall was measured. Good correlation was observed with the data by ultrasound cardiography (r = 0.79, p < 0.002 in wall thickness, r = 0.84, p < 0.01 in the ratio of septal wall thickness to free wall thickness). Left ventricular shape (ventricular long axis) was closely resemble to that of left ventriculography by contrast medium. In conclusion, 99mTc-Tetrofosmin scintigraphy is useful for the evaluation of myocardial morphology as well as perfusion abnormality.

Adult↗

Angiotensin converting enzyme inhibitors or DuP753 prevent neointimal formation following balloon injury with single topical or multiple systemic application.

Angiotensin II plays an important role in neointimal formation after vascular injury. Our objectives were 1) to investigate the difference between angiotensin converting enzyme inhibitors (captopril, delapril) and an angiotensin II subtype 1 (AT1) receptor antagonist (DuP753) in suppressing neointimal proliferation; and 2) to investigate the antiproliferative effects of these drugs given topically to the injured vessels. All these treatments effectively prevented neointimal formation (p < 0.01). Even a single topical application of either type of drug with F127 pluronic gel to be injured vessel after ballooning is found to be significantly effective probably due to the inhibition of smooth muscle cell migration (p < 0.01). Multiple systemic application of angiotensin converting enzyme inhibitors was more effective than that of DuP753 at the same blood pressure level. The effectiveness of topical application of these drugs suggests clinical usefulness after angioplasty or vascular surgery.

Administration, Topical↗

Activation of the zymogen of hepatocyte growth factor activator by thrombin.

Hepatocyte growth factor activator (HGF activator) is a serine protease which converts single-chain HGF to the active two-chain form. HGF activator purified from human serum has a molecular mass of 34 kDa and consists of two chains held together by a disulfide bond. The nucleotide sequence of HGF activator cDNA shows that HGF activator is derived from the COOH-terminal region of a precursor of 655 amino acids by proteolytic cleavage of the bonds between Arg372 and Val373 and between Arg407 and Ile408 and that the precursor consists of multiple domains homologous to those observed in blood coagulation factor XII. In this study, we identified the precursor of HGF activator in human plasma using an enzyme-linked immunosorbent assay system. The precursor was purified from plasma by a five-step procedure. The purified precursor did not activate single-chain HGF. The precursor was efficiently cleaved in vitro by thrombin, at the bond between Arg407 and Ile408, in the presence of negatively charged substances. The cleaved precursor activated single-chain HGF. These findings led us to conclude that HGF activator is present in plasma as an inactive zymogen and that the zymogen is activated by the cleavage of the bond between Arg407 and Ile408 by thrombin. Characteristic structural domains in the NH2-terminal region of the zymogen may be involved in the binding of the zymogen to negatively charged substances, which stimulates the activation of the zymogen by thrombin.

Amino Acid Sequence↗

Rare frequency of activation of the Ki-ras gene in rat colon tumors induced by heterocyclic amines: possible alternative mechanisms of human colon carcinogenesis.

Heterocyclic amines present in cooked foods are known to produce colon tumors in F344 rats at a high incidence, indicating the possibility of involvement of ras gene activation in colon carcinogenesis in rats as in humans. We examined mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes by polymerase chain reaction--direct sequencing in seven colon tumors in F344 rats induced by 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1), 11 induced by 2-amino-3-methylimidazo[4,5-f]quinoline, and nine induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. A Ki-ras gene mutation (G-->T at the second position in codon 12) was found in one Glu-P-1-induced colon adenocarcinoma. None of the other 26 tumors had mutations in any of these three ras family genes. These results indicate that in rats, colon carcinogenesis induced by heterocyclic amines may be induced by alterations of other oncogenes or tumor suppressor genes. We think this experimental system using carcinogens to which humans are exposed is a good model for studying alterations of other genes in human colon tumors in which no Ki-ras alterations are observed.

Adenocarcinoma↗

Morphological changes of small pancreatic cysts in response to secretin stimulation. Observation by endoscopic ultrasonography.

It is difficult to discriminate clinically the etiology of small pancreatic cysts using conventional methods. Endoscopic ultrasonography can delineate small lesions. In order to help differentiate the etiology of cystic lesions of the pancreas by endoscopic ultrasonography, we investigated morphological changes following stimulation of the pancreatic secretion with secretin. After an intravenous injection of secretin (50 CU), the size, shape, and echogenicity of a cyst smaller than 2 cm were recorded for 15 min. Of 17 cases examined, 10 patients showed an alteration of these factors. These cases were thought to be nonneoplastic cysts, which included all six cases where communication to the main pancreatic duct was demonstrated by ERCP. Five cases of neoplastic cyst did not show the change in shape and size. These results indicate that secretin stimulation provides useful information in the diagnosis of the etiology of pancreatic cyst by endoscopic ultrasonography.

Aged↗

Identification of N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethyl-imidazo[4,5- f]quinoxaline 3',5'-diphosphate, a major DNA adduct, detected by nuclease P1 modification of the 32P-postlabeling method, in the liver of rats fed MeIQx.

The carcinogenic heterocyclic amine 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) is widely distributed in cooked foods. The nuclease P1 method increased the sensitivity of the standard 32P-postlabeling analysis about 1000-fold for detection of MeIQx-DNA adducts. The recovery of MeIQx-DNA adducts by the nuclease P1 method was determined to be about 50% using liver DNA of a rat treated with [14C]MeIQx intragastrically. By the nuclease P1 method five adducts were detected in the liver DNA of rats fed MeIQx and two of them, including the most abundant one, were identified as MeIQx-deoxyguanosine adducts by comparison with the adducts formed in in vitro reactions of N-acetoxy-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline with the four 2'-deoxyribonucleotides. The most abundant adduct in vivo was identified as N2-(deoxyguanosin-8-yl)-MeIQx 3',5'-diphosphate (3',5'-pdGp-C8-MeIQx). MeIQx-DNA adduct levels in human tissues could be determined by the nuclease P1 modification of the 32P-postlabeling method in combination with HPLC, and thus provide information on the roles of MeIQx in human carcinogenesis.

Animals↗

Effects of chronic administration of low doses of 2-amino-3,8-dimethylimidazo-[4,5-f]quinoxaline on glutathione S-transferase placental form-positive foci development in the livers of rats fed a choline-deficient diet.

Effects of chronic administration of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) at the very low doses of 0.4 and 4 ppm, respectively 1000- and 100-fold less than the dose shown to be carcinogenic (400 ppm), on the liver of rats fed a choline-deficient (CD) diet were examined in terms of glutathione S-transferase placental form (GST-P)-positive foci. Male F344 rats were given CD diet containing 0, 0.4 or 4 ppm MeIQx for 20 or 40 weeks. As controls, rats received choline-supplemented (CS) diet in the same manner. MeIQx at 4 ppm in the CD diet significantly increased both the number and area of GST-P-positive foci, the values being 2.3- and 2.1-fold at 20 weeks and 2.0- and 3.3-fold at 40 weeks, respectively, compared with those observed for CD diet alone. MeIQx at 0.4 ppm in CD diet did not affect the development of GST-P-positive foci. No influence of the heterocyclic amine was found in the CS groups, where only very small numbers of minute lesions were observed. The level of MeIQx-DNA adducts in rats given the CD diet containing 4 ppm MeIQx was 2- to 3-fold lower than that in rats given the CS diet containing 4 ppm MeIQx at 20 and 40 weeks. This result indicates that DNA adduct formation and cell proliferation are both required for the increase of GST-P-positive foci in rats fed 4 ppm MeIQx in a CD diet. The above findings strongly suggest that MeIQx could be carcinogenic even at 4 ppm under CD conditions, where liver cell regeneration is continuously occurring.

Animals↗

Exposure to heterocyclic amines.

Many mutagenic heterocyclic amines (HAs) have been isolated from cooked foods and pyrolysates of amino acids and proteins, and the carcinogenicity of 10 of these HAs in rodents and of 1 in monkeys has been reported. Quantification of these carcinogenic HAs in various kinds of cooked foods indicated that the level of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was highest (0.56-69.2 ng/g), that of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was second highest (0.64-6.44 ng/g), and those of other HAs were 0.03-2.50 ng/g. Heterocyclic amines were found in urine samples of 10 healthy volunteers consuming a normal diet, but HAs were not detectable in urine samples of three patients receiving parenteral alimentation. These results strongly suggest that humans are continuously exposed to HAs derived from food in the normal diet. Based on quantitative data on the levels of HAs in cooked foods and urine samples, the daily exposures to PhIP and MeIQx were estimated to be 0.1-13.8 micrograms and 0.2-2.6 micrograms per person, respectively. These levels of carcinogenic HAs are in the same range as those of other carcinogens such as N-nitrosodimethylamine and benzo[a]pyrene to which humans are exposed.

Adolescent↗

Ultrasonographic follow-up study of small pancreatic cysts of unknown etiology.

The aim of the present project was to evaluate the prognosis of small and asymptomatic cysts of the pancreas which were diagnosed as being nonneoplastic by endoscopic ultrasonography. Eighty-two patients with such cysts had been subjected to ultrasonographic examination every 6 months. Results of follow-up for 3 or more years were obtained in 31 patients. The cysts disappeared in 4 patients and enlarged in 1 patient. The others did not show any morphological changes. The enlarged cyst turned out to be a retention cyst after surgical resection. Our endoscopic ultrasonographic criteria were effective for small nonneoplastic cysts of the pancreas, and most of these cysts appeared to be nonprogressive.

Adult↗

[Digitalis for the treatment in patients with heart failure].

Digitalis glycosides are the first-choice drugs in the treatment of the patients with congestive heart failure and atrial fibrillation. Recently, it has been shown that digitalis glycosides have potentially beneficial neurohumoral modulating effects by decreasing excessive neurohumoral responses directly or by improving baroreflex mechanisms in congestive heart failure. Accordingly, there are many investigators who believe that digitalis glycosides are neurohormonal modulating agents in heart failure. There may be a dissociation between hemodynamic and neurohormonal effects in response to digitalis glycosides. The activation of the neurohormonal system may be present in patients with asymptomatic left ventricular dysfunction. Digitalis glycosides may therefore be used, not only to improve symptomatic congestive heart failure, but also to protect against the progressive deterioration of asymptomatic cardiac dysfunction.

Atrial Natriuretic Factor↗

[Effects of propafenone on the parameters of body surface electrocardiogram in comparison with those of disopyramide].

The purpose of this study is to investigate the clinical effects of propafenone on the QT(QTc), QRS, PQ and RR interval of body surface electrocardiogram (ECG) in comparison with the effects of disopyramide. In 10 patients (5 with paroxysmal atrial fibrillation and 5 with ventricular premature complex: ages 48-77), after 4 days' observation without any cardioactive drugs, disopyramide (300mg/day) was administered orally for 7 days. After discontinuing the administration of disopyramide, 4 more days were allowed to wash out the drug, and propafenone (450mg/day) was administered orally for 7 days. 12-lead ECG was taken twice before the administration of disopyramide (Pre-1 and -2), on the 1st, 3rd, 5th and 7th days after the administration of disopyramide. Then it was also taken on the day before the beginning of propafenone administration and on the 1st, 3rd, 5th and 7th days after the administration of propafenone. The corrected QT (QTc = QT/square root of RR), QRS, PQ and RR intervals in lead II or V2 of each ECG were measured as the mean value of 5 consecutive sinus beats. The control values of QTc, QRS, PQ and RR intervals were calculated as the mean values of Pre-1 and -2, and the other values were expressed as the % ratio to the control values. Propafenone hardly altered the QTc interval but prolonged QRS interval after the 5th day of administration (110 +/- 12%, p < 0.05), while disopyramide significantly prolonged the QTc interval after the 3rd day of administration (109 +/- 5%, p < 0.001) without affecting the QRS interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Detection of a Ha-ras point mutation by polymerase chain reaction-single strand conformation polymorphism analysis in 2-amino-3,4-dimethylimidazo[4,5-f]quinoline-induced mouse forestomach tumors.

Ha-ras activation in forestomach squamous cell carcinomas of CDF1 mice induced by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), one of the heterocyclic amines isolated from broiled sardine was analyzed. Mutations were detected in two of three primary original carcinomas and two of four cell lines derived from other independent carcinomas by the polymerase chain reaction followed by analysis of single strand conformation polymorphism and direct sequencing. All the mutations detected were G----T transversions at the second letter of codon 13 resulting in an amino acid change from Gly to Val. This finding together with the previous reports on squamous cell carcinomas of the rat Zymbal gland suggest that MeIQ induces a specific type of mutation at a specific site of the Ha-ras gene during squamous cell carcinogenesis, in a species-independent manner.

Animals↗

Immunocytochemical localization of beta-1,3-glucan recognition protein in the silkworm, Bombyx mori.

A monospecific antibody against beta-1,3-glucan recognition protein (a 62 kDa protein) of the larval silkworm prophenoloxidase activating system was used to study the localization of the protein. Among tissues from 5th instar larvae, only hemocytes and plasma were shown to contain a 62 kDa polypeptide immunoreactive with the antibody. Ultra-thin sections of the hemocytes were stained by an indirect immunogold staining method. Labelling occurred in the granules and cytoplasm of granulocytes and in the spherules and cytoplasm of spherulocytes. It was most conspicuous in granules of granulocytes and uniformly labelled spherules of spherulocyte, whereas no labelling was evident in prohemocytes, plasmatocytes and oenocytoids. The results are discussed in relation to the mode of recognition of fungi as non-self in insect hemocoel.

Animals↗