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Biomedical subjects

H Kano

Publications and source records attributed to H Kano.

At least 127 records · Page 7Linked to original sources

Effect of an AT1 receptor antagonist (CV-11974) on angiotensin II-induced cardiomyocyte hypertrophy in vitro.

Angiotensin (ANG) II, a potent vasoconstrictor is known to be a hypertrophic factor for cardiomyocytes. Recently, endothelin (ET)-1 has also been shown to be an autocrine/paracrine growth factor for cardiomyocytes. To determine the cellular mechanism by which ANG II induces cardiac hypertrophy, we studied the effects of ANG II on the gene expression of ET-1 and ET receptor subtypes (ETA, ETB), as well as its effects on the expression of immediate early oncogenes (c-fos, c-myc) in cultured rat cardiomyocytes in vitro. ANG II (10(-7) M) increased steady-state mRNA levels of ET-1 in the same manner as c-fos and c-myc during a short incubation period (0.5-1 h), while ANG II induced ETB receptor mRNA, but not ETA receptor mRNA, during a long incubation period (6-12 h). CV-11974, an antagonist of ANG II receptor type-1 (AT1), inhibited the ANG II-induced expression of c-fos, c-myc and ET-1 mRNAs, as well as that of ETB receptor mRNA, whereas PD-123319, an antagonist of the ANG II type-2 (AT2) receptor, failed to block such induction. CV-11974 similarly blocked ANG II-induced immediate-early oncogenes (c-fos, c-myc) in cultured rat vascular smooth muscle cells. Our findings indicate that ANG II immediately upregulates the cardiac ET-1 gene in the same manner as it does the immediate early protooncogenes, while the late induction of the ETB receptor, mainly via the cardiac AT1 receptor, suggests the involvement of endogenous ET-1 in ANG II-induced cardiac hypertrophy.

Angiotensin II↗

Relationship between the regression of left ventricular hypertrophy and the changes in circadian blood pressure after long-term treatment with enalapril in hypertensive patients.

The ambulatory blood pressure (BP) was recorded for 24 hours in 28 untreated hypertensive patients, and mean values of systolic (SBP) and diastolic BP (DBP) were measured over 24 hours, during the day-time (6:00 to 19:30), and during the night-time (20:00 to 5:30). M-mode echocardiography was performed and several parameters of left ventricular size were calculated. In addition, 13 men of 18 patients with left ventricular hypertrophy (LVH) received long-term treatment with enalapril, and ambulatory BP monitoring and echocardiographic measurement were performed in 10 of these patients 6 months after active treatment ended. In all 28 patients, left ventricular mass index (LVMI) was significantly related to 24-hour, day-time and night-time SBP. Other parameters of hypertrophy were correlated with 24-hour and/or night-time BP, but not with day-time BP. In patients with LVH, night-time DBP was significantly higher and the night-time decline in DBP was significantly less than in those without LVH. The 6-month treatment with enalapril clearly decreased casual and ambulatory BP and reduced LVMI. The reduction of LVMI was strongly correlated with the decrease in night-time SBP and DBP compared with the decrease in day-time BP. These observations indicate that LVH is related to 24-hour BP (especially night-time BP) and that the regression of this condition may be related to a decline in night-time BP.

Adult↗

[Relationship between abdominal fat distribution assessed by computed tomography and serum lipids in the elderly].

A nutritional assessment is necessary to evaluate the pathophysiological state of patients, and serum lipids are one of the factors which must be evaluated. Body fat distribution is considered to be associated with cardiac diseases, metabolic diseases and hypertension. In this study, we performed quantitative measurements of fat distribution by X-ray computed tomography (CT) in 31 elderly outpatients. Thirteen males (mean age 74.8 years) and 18 females (mean age 75.4 years) were examined by abdominal CT. All subjects had body mass indices within the normal range and did not have malignant disease, hyperlipidemia, liver dysfunction or diabetes mellitus. CT scans were carried out at the level of the middle abdomen; these scan slices included intraabdominal fat which consisted of omental, retroperitoneal and perirenal adipose tissues. Subcutaneous fat areas and intraabdominal fat areas were measured from six 10-mm-thick slice films using a 2-dimensional computerized calculator. The relationship between serum lipids and fat distribution was also examined. The ratio of intraabdominal adipose tissue area to subcutaneous adipose tissue area (V/S) was higher in males than in females. V/S correlated positively with serum triacylglycerol and correlated negatively with serum HDL-Ch. These results suggest that the measurement of body fat distribution is important to evaluate lipid metabolism and nutritional states in the elderly.

Adipose Tissue↗

Depression of drug-metabolizing activity in the human liver by interferon-beta.

The depressant effect of interferon beta on drug-metabolizing activity in the human liver was investigated. Seven patients with chronic hepatitis C were treated with interferon beta at doses of 3 x 10(6) to 9 x 10(6) IU/day for 8 wk. The activities of 7-methoxycoumarin O-demethylase and 7-ethoxycoumarin O-deethylase in specimens obtained by liver biopsy were examined before and after interferon treatment. Theophylline pharmacokinetics were also examined before and after interferon treatment. Interferon beta treatment reduced the activities of both O-dealkylases from 6.0 (100%) to 3.2 (53%) nmol/gm liver per minute and from 1.9 (100%) to 1.1 (58%) nmol/gm liver per minute, respectively (p < 0.05). The total body clearance of theophylline was also decreased (from 0.76 to 0.56 ml/kg/min; p < 0.05), and its elimination half-life was increased (from 8.4 to 11.7 hr; p < 0.05); however, the volume of distribution was not significantly affected. The magnitude of the decreases in enzyme activities and in theophylline clearance varied widely in individual patients and did not correlate with the dose of interferon administered. This study provides the first direct evidence that interferon beta can depress the activity of drug-metabolizing enzymes in the human liver.

7-Alkoxycoumarin O-Dealkylase↗

Nucleotide sequence of capsid protein gene of rice tungro bacilliform virus.

The sequence of 5,028 nucleotides, including one open reading frame (ORF), of rice tungro bacilliform virus (RTBV) dsDNA was determined. The predicted translational product comprises 1,675 amino acids and has Mr of 194,134 (p194). The amino acid sequences of three tryptic fragments from the 32 k capsid protein of RTBV (p32) were found in the predicted translational product indicating that the ORF codes for the RTBV capsid protein.

Amino Acid Sequence↗

Zinc deficient bovine erythrocyte superoxide dismutase has low specific activity.

Zinc deficient bovine superoxide dismutase (Cu2E2SOD (E = empty)) was prepared and purified by high performance liquid chromatography (HPLC). Each peak was characterized as to protein, copper content and specific activity. The Cu2E2SOD peak fractionated by HPLC has a low specific activity at pH 7.8 (about 10% of the native enzyme (Cu2Zn2SOD)). With the addition of zinc ions, the specific activity of Cu2E2SOD was quantitatively restored to that of the native enzyme. This behavior implies that the zinc ion is very important for the appearance of enzyme activity.

Animals↗

Crystallization and preliminary X-ray study of a double-shelled spherical virus, rice dwarf virus.

Rice dwarf virus (RDV) is a double-shelled spherical plant virus consisting of 46,000 Mr capsid and 114,000 Mr core proteins and minor structural proteins, and containing 12 genome segments of double-stranded RNA. The virus has been crystallized in the cubic space group I23 with a = 789 A. There are two particles per unit cell, each positioned on a point of 23 symmetry. Packing considerations showed that the diameter of the virus particle is 693 A. The crystals diffract to at least 6.5 A resolution.

Capsid↗

[Risk of hepatitis C virus infection by needlestick among medical employees].

We have experienced 99 medical employees who had stuck themselves by the needles used by patients in the past 5 years. Sixteen of the 99 cases (16.2%) were of the patients who had hepatitis C Virus (HCV) antibodies. We followed up these 16 medical employees during 24.8 +/- 12.0 months. We could not find any case among them who had seroconverted HCV antibody positive in their serums. We concluded that the risk of HCV infection by the needlestick accident is not so high.

Adult↗

[An MRI and SPECT study of frozen gait without other manifestations of parkinsonism in the elderly].

The authors have sometimes experienced cases of frozen gait without any other manifestations of parkinsonisms in the elderly, so we examined these cases using MR imaging and SPECT imaging. The group with frozen gait (4 cases, aged 78 to 82 years) which failed to respond to L-dopa therapy, had no limb-kinetic apraxia or frontal signs, but did exhibit "kinésie paradoxale". The clinical symptoms of case 4 were consistent with so-called "pure akinesia". CT findings in this group failed to elucidate the pathogenesis of frozen gait. MR imaging of all of the cases except for the case of pure akinesia (case 4) revealed a high signal intensity areas in subcortical lesions (especially the frontal area). Case 4 had only a few spotty high-signal intensity areas. We then compared 6 cases which have the same lesions (on MRI) as cases 1-3 without frozen gait in cases 1-3 using 123I-IMP SPECT. Relatively low accumulation of radionuclide in the frontal area was observed in these cases. Case 4 had a slightly low perfusion area in the frontal lobe. However in the patient treated with L-threo-DOPS, accumulation of radionuclide in the frontal area increased slightly after L-threo-DOPS therapy. It appears that one of the reasons for frozen gait in the elderly is incomplete infarct of the subcortical white matter with a low perfusion area in the frontal cortex. Furthermore, in some cases of frozen gait it is difficult to distinguish between cases with white matter disorders and cases of pure akinesia on the basis of clinical symptoms and CT alone.

Amphetamines↗

Depression of drug metabolizing activity in the human liver by interferon-alpha.

The depressant effect of interferon-alpha on drug metabolizing activity in the liver has been investigated in 12 patients with chronic active hepatitis B. 7-methoxy-coumarin (7-MC) O-demethylase and 7-ethoxycoumarin (7-EC) O-deethylase, in specimens obtained by liver biopsy, were measured before and after interferon treatment. 7-MC and 7-EC O-dealkylase activity were significantly reduced after interferon treatment, from 13.4 to 9.24 nmol.g-1 liver.min-1, and from 3.22 to 2.16 nmol.g-1 liver.min-1, respectively. The magnitude of the fall varied widely between individual patients. The study provides the first direct evidence that interferon-alpha can impair the activity of drug metabolizing enzymes in the human liver.

7-Alkoxycoumarin O-Dealkylase↗

Occurrence of immunohistochemically detected small Mallory bodies in liver disease.

To determine the diagnostic significance of immunohistochemically detected small Mallory bodies (MBs) which are invisible by conventional stainings, we investigated the occurrence of MBs in liver tissue with alcoholic and nonalcoholic liver disease by immunoperoxidase staining with monoclonal anti-MB antibody, anti-NMB-3. In conventional stainings, MBs were detected in only six of 26 (23%) patients with alcoholic liver disease, and nine of 63 (14%) patients with nonalcoholic liver disease. On the other hand, MBs were detected in 20 of 26 (77%) patients with alcoholic liver disease, and 25 of 63 (40%) patients with nonalcoholic liver disease by immunoperoxidase staining. Immunohistochemically detected MBs were shown to possess the ultrastructural characteristics of MBs by immunoelectronmicroscopy in the four specimens. Our result indicates that the small MBs are not rare in nonalcoholic liver disease, and the presence of immunohistochemically detected small MBs is not a good marker of an alcoholic etiology.

Adolescent↗

Experimental study on significance of QRS area map--comparison with VAT map.

The QRS area map, which is obtained by time integration of the QRS potential, is assumed to correlate with the ventricular activation time (VAT) map. Using 16 mongrel dogs, the QRS area map and VAT map from cardiac and body surface were compared during sinus rhythm and left and right ventricular endocardial pacing. The cardiac surface QRS area map resembled the cardiac surface VAT map, and it was considered useful to estimate the excitation sequence. The body surface QRS area map localized the stimulus site more easily during pacing than the body surface VAT map. Therefore, it was considered useful to determine the site at which a ventricular extrasystole occurs. The QRS area map proved to be more reproducible than the VAT map.

Animals↗

Danazol binds to progesterone receptors and inhibits the growth of human endometrial cancer cells in vitro.

Based on our recent findings that danazol, an isoxazol derivative of ethinyltestosterone, has a profound growth-inhibitory effect on an established human endometrial adenocarcinoma cell line, the effects of danazol on cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were investigated in the present study. Of the 22 uterine adenocarcinomas, estrogen, progesterone, and androgen receptors were found in 12, 14, and 4 tumors, respectively. Competitive binding studies showed that danazol specifically binds to progesterone and androgen receptors but not to estrogen receptors. Of the five cancer cells from five patients succeeded in primary cell culture, a marked inhibition of cell growth was demonstrated by addition of danazol in two cancer cells having progesterone but not androgen receptors. However, danazol did not affect the growth of the remaining three cancer cells lacking progesterone receptors. These results strongly suggest that danazol has a significant growth-inhibitory effect on human endometrial adenocarcinoma cells, possibly through progesterone receptors in the cells.

Adenocarcinoma↗

Long-term investigation of habitual tonsillitis in children.

The authors were in close contact with children who had indications for tonsillectomy and investigated them in both acute tonsillitis and intermittent periods of tonsil inflammation. The results obtained were as follows: Repeated attacks of acute tonsillitis clearly decreased in number. No secondary diseases due to tonsillitis were observed. When repeated attacks of acute tonsillitis occurred, the symptoms were not as serious as previously.

Adolescent↗

[Phase II study of epirubicin on gastric cancer--a cooperative study of the Tokai Cancer Chemotherapy Group].

A phase II study of epirubicin, a new anthracycline derivative, was performed in 23 patients with advanced gastric cancer. Epirubicin was administered intravenously at a dose of 20-30 mg/m2/day for two or three consecutive days every two or three weeks. Sixteen cases were evaluable and there were two partial responses and one minor response. Overall response rate (more than PR) was 12.5% (2/16). Leukopenia (less than 4,000/mm3) and anemia (less than 11.0 g/dl) were observed in 71.4% and 69.2% of patients, respectively. No thrombocytopenia was observed. Other toxicities were alopecia (71.4%), nausea and vomiting (42.9%), anorexia (25.0%), stomatitis (12.5%), fatigue (12.5%), fever (6.3%) and tachycardia (6.3%), but these effects were relatively mild in most cases.

Adenocarcinoma↗