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Biomedical subjects

S Sakamoto

Publications and source records attributed to S Sakamoto.

At least 559 records · Page 31Linked to original sources

Effect of continuous intravesical infusion of low-concentrated mitomycin-C on bladder carcinogenesis in rats treated with N-butyl-N-4-hydroxybutyl-nitrosamine.

In the first experiment, histological changes of urinary bladder after long-term transvesical catheterization were evaluated in normal rats. No malignant changes of the bladder epithelium were detected in the two and four-week catheterization groups. However incidences of papilloma and papillary carcinoma developed in three of the five rats (60%) in the eight-week group. In a second experiment the therapeutic effect of continuous or intermittent administration of MMC on bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. MMC at a total dose of four mg. was administered for two weeks in both therapeutic groups. Continuous infusion was performed transvesically using an osmotic pump and a silicone catheter, on the basis that preliminary examination revealed the urinary delivery rate of MMC was constant for two weeks. In the intermittent group, MMC solution was instilled transurethrally with a venural catheter twice a week. The continuous infusion of low concentrated MMC reduced significantly (p less than 0.02) the incidence of tumor development in spite of extended catheterization (for eight weeks) into the bladder. However, the intermittent instillation of high concentrated MMC hardly inhibited the development of bladder tumors. We should consider the optimal concentration and time of a drug in intravesical chemotherapy based on the above findings.

Administration, Intravesical↗

Dynamic determination of kinetic parameters for the interaction between polypeptide hormones and cell-surface receptors in the perfused rat liver by the multiple-indicator dilution method.

Hepatic elimination of epidermal growth factor (EGF) via receptor-mediated endocytosis was studied by a multiple-indicator dilution method in the isolated perfused rat liver, in which cell polarity and spatial organization are maintained. In this method EGF was given with inulin, an extracellular reference, as a bolus into the portal vein, and dilution curves of both compounds in the hepatic vein effluent were analyzed. Analysis of the dilution curve for EGF, compared with that for somatostatin, which showed no specific binding to isolated liver plasma membranes, resulted as follows: (i) both extraction ratio and distribution volume of 125I-labeled EGF decreased as the injected amount of unlabeled EGF increased; (ii) the ratio plot [ln (inulin/EGF) versus time] of the dilution curve for EGF exhibited an upward straight line initially for a short period of time (approximately equal to 10 sec), whereas the ratio plot [ln (inulin/somatostatin) versus time] of somatostatin gradually decreased. The multiple-indicator dilution method was used for other peptides also. Insulin and glucagon, known to have hepatocyte receptors, behaved similarly to EGF in shape of their ratio plots. Thus, analysis of dilution curves can reveal whether or not the cell surface has receptors for certain peptides. In addition, the dilution curves for EGF at various doses (tracer approximately equal to 30 micrograms) were analyzed simultaneously based on a kinetic model incorporating the perfusion rate, the association rate constant of EGF to surface receptors (kappa on), the dissociation rate constant of EGF from the EGF-receptor complex (kappa off), and the sequestration rate constant of the complex. The kinetic parameters [the dissociation constant (Kd = kappa off/kappa on) and the number of surface receptors] calculated by this analysis were comparable with reported values obtained by in vitro direct binding measurements at equilibrium using liver homogenates. We conclude that the multiple-indicator dilution method is a good tool for analyzing the dynamics of peptide hormones--cell-surface receptor interaction under a condition in which spatial architecture of the liver is maintained.

Algorithms↗

Dynamic behaviour of coronary stenosis in response to increasing heart rate in the dog.

In order to assess the responses of coronary stenosis to an elevation of myocardial metabolic demand, the effects of pacing induced tachycardia on systemic and coronary haemodynamics were examined during four grades of compliant coronary stenosis which preserved stenosis vasomotility in eight open chest dogs. Grades of the coronary stenosis were defined as trifling, mild, moderate, and severe by pressure gradients of 12(0.5), 19(1.0), 28(1.4) and 37(1.6) mm Hg (mean [SEM]), respectively. Stepwise increases in heart rate (+30, +60 and +90 beats.min-1) decreased the resistance caused by trifling and mild coronary stenosis by 47(11.9) and 26(8.8)%, respectively, with an increase in coronary blood flow and a decrease in pressure gradient across the stenosis. By contrast, the resistance caused by moderate and severe stenosis increased by 96(24.2) and 148(63.2)%, respectively, with a decrease in coronary blood flow and an increase in pressure gradient. During lower grades of coronary stenosis, flow-dependent dilatation of large epicardial coronary arteries reduced the stenosis severity, whereas during higher grades of stenosis, passive narrowing of the stenosed arterial segment due to arteriolar vasodilatation outstripped the flow-dependent stenosis dilator effects and resulted in an intensification of the stenosis.

Animals↗

Effect of ba-wei-di-huang-wan (hachimi-jio-gan) on thymidine kinase and its isozyme activities in the prostate glands in rats.

Ba-wei-di-huang-wan (Hachimi-jio-gan, TJ-7) has been frequently used for the treatment of sterilitas virilis, prostatic disorders, etc. The hormonal effects of TJ-7 were studied using thymidine kinase (TK), an enzyme that catalyzes the phosphorylation of thymidine via the pyrimidine salvage pathway. TK isozyme activity increases in rapidly proliferating tissues. TJ-7 may act as a weak androgen and enhance prostatic TK and in particular, a specific TK isozyme activity, and also as an anti-androgen and reduce prostatic TK activity in the presence of androgen in immature rats.

Animals↗

Cytomegalovirus gastritis as an initial manifestation of a patient with adult T-cell leukemia.

A 39-year-old woman was admitted to the hospital because of epigastric pain and diagnosed as having gastritis. After 3 months, she developed generalized lymphadenopathy, and a biopsy revealed diffuse proliferation of CD4 positive lymphoid cells. She was positive for human T-cell leukemia virus type-I antibody and the diagnosis of lymphoma-type adult T-cell leukemia (ATL) was made. Gastritis was proved to be caused by cytomegalovirus (CMV), since histologic examination of the gastric biopsy specimen disclosed typical cytomegalic inclusions. CMV infection in ATL patients is usually generalized and complicated at the terminal phase of the disease. This patient had an unusual form of CMV infection which showed isolated stomach involvement; it preceded the full appearance of ATL and thus was the initial manifestation of the disease.

Adult↗

Comparative effects of nitroprusside and pinacidil on myocardial blood flow and infarct size in awake dogs with acute myocardial infarction.

The effect of nitroprusside in limiting myocardial infarct was compared with that of pinacidil, a new antihypertensive agent with potent coronary vasodilator properties, in instrumented awake dogs subjected to 4 hr of left anterior descending coronary artery occlusion and 20 hr of reperfusion. Dogs were randomly assigned to receive intravenous normal saline, nitroprusside, or pinacidil beginning 40 min after the onset of coronary artery occlusion and continuing throughout the occlusion and the first hour of reperfusion. Nitroprusside and pinacidil were titrated to decrease mean aortic pressure by 25 mm Hg; normal saline had no effect on mean aortic pressure. Other systemic hemodynamic variables were not significantly altered by normal saline or nitroprusside, and myocardial blood flow did not change during normal saline infusion in normal and ischemic myocardium. In contrast, nitroprusside increased the blood flow and the endocardial/epicardial flow ratio in ischemic myocardium. This increase in ischemic myocardial blood flow was accompanied by a significant reduction in infarct size (40 +/- 3% of region at risk vs 58 +/- 4% in the normal saline group; p less than .05). Pinacidil increased heart rate, cardiac output, and the peak rate of rise of left ventricular pressure. Furthermore, despite causing a threefold to fourfold increase in normal myocardial blood flow, pinacidil had no effect on either blood flow to ischemic myocardium or infarct size (57 +/- 5%). The data indicate that the marked coronary vasodilator effect of pinacidil does not cause an increase in ischemic blood flow or a reduction in infarct size.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Short-term hemodynamic effects of vasopressin V1-receptor inhibition in chronic right-sided congestive heart failure.

Arginine vasopressin is elevated in congestive heart failure. To determine the effect of arginine vasopressin upon systemic hemodynamics and regional blood flows, we administered the specific inhibitor of the vascular action of vasopressin [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-methyl)-tyrosine]-arginine vasopressin [d(CH2)5Tyr(Me)AVP] to 15 dogs with chronic right-heart failure produced by tricuspid avulsion and progressive pulmonary artery constriction. The animals exhibited increased plasma arginine vasopressin and norepinephrine levels. Vasopressin inhibition increased cardiac output and left ventricular dP/dt and dP/dt/P, and it decreased total peripheral vascular resistance, whereas mean aortic pressure did not change significantly. Simultaneously, blood flow increased to skeletal muscle, kidneys, skin, and right and left ventricular myocardium. Plasma catecholamines also increased. Pretreatment with propranolol and prazosin abolished the increases in cardiac output and left ventricular function produced by vasopressin inhibition. Pretreatment also led to a decrease in mean aortic pressure after vasopressor inhibition. In contrast, administration of d(CH)2)5Tyr(Me)AVP to 11 sham-operated animals or administration of normal saline to nine sham-operated and eight heart-failure dogs was without effect either in the absence or in the presence of adrenergic receptor blockade. Thus, arginine vasopressin participates in the control of the circulation in right-sided congestive heart failure, with both a direct constrictor action on blood vessels and an indirect action by inhibition of the sympathetic nervous system.

Animals↗

Radioimmunoassay of human epidermal growth factor--hEGF levels in human body fluids.

By immunizing rabbits with purified human epidermal growth factor (hEGF), which was synthesized by Escherichia coli constructed by a genetic engineering technique, high titer antiserum for hEGF was obtained. The antiserum has an excellent specificity to hEGFs (hEGF, hEGF [1-51], hEGF [1-47] and [Leu21] hEGF) and has almost no cross-reactivity with other biological peptides, such as mouse EGF and human platelet derived growth factor. Using radioiodinated hEGF, a radioimmunoassay (RIA) for hEGF was established by a double antibody-polyethylene glycol method. As little as 10 pg/tube of hEGF was successfully determined by the present RIA methods. The intra- and inter-assay coefficients of variation for hEGF in human plasma or serum were 2.4-4.9% and 3.7-6.2%, respectively. The hEGF levels in human body fluids determined by the present method were as follows: urine (11-100 ng/ml), serum (1.0-1.8 ng/ml), plasma (0.2-0.8 ng/ml), sperm (17-47 ng/ml), saliva (0.9-3.0 ng/ml) and tears (9.5-27 ng/ml).

Adult↗

Mitral valve and its ring in hypertrophic cardiomyopathy--a mechanism creating surplus mitral leaflet involved in systolic anterior motion.

A large surplus portion of the mitral leaflets appears to be involved in the systolic anterior motion (SAM) of the mitral valve in hypertrophic cardiomyopathy (HCM). To understand the exact features and the mechanism of the surplus leaflet, we studies the mitral valve and its ring quantitatively with two-dimensional echocardiography in 17 patients with HCM (5 with large SAM, 6 with small SAM and 6 without SAM) and 10 normal subjects. In the large SAM group, the surplus length of the anterior mitral leaflet (AML) increased but that of the posterior mitral leaflet (PML) did not increase when compared to the other 3 groups. In the large SAM group, the length of AML was greater than in the normal group and the length of PML was greater than in the other 3 groups. The mid-systolic anteroposterior diameter of the mitral ring did not differ among the 4 groups. The mid-systolic position of the coaptation was more anterior in the large SAM group than in the other 3 groups. In conclusion, the surplus size of AML is actually increased in the patients with HCM and large SAM, which is caused by the elongation of both AML and PML with anteriorly displaced coaptation and with no dilation of the mitral ring.

Adolescent↗

[Estimation of absorbed dose in 131I therapy of metastasis of thyroid cancer].

The radiation absorbed dose was estimated for 131I therapy of metastatic lesions of thyroid cancer, by the quantitative gamma-camera imaging. Uptake for eleven lesions in five cases (out of four patients) was measured for two times after 131I administration. Activities were calculated from opposed images with corrections for distance and depth using empirical formulae. An activity time curve was assumed as a reminder of two exponentials and fitted to measured values. The sizes of lesions were evaluated using the multi-slice CT images. An increase of frequency of activity measurement, particularly within a few days after 131I administration is desirable, for the purpose of an improvement of accuracy of dosimetry.

Bone Neoplasms↗

Collagenase synthesis in clonal monkey kidney epithelial cells (JTC-12 cells).

Cells of clone JTC-12 derived from monkey kidney epithelial cells were found to produce latent collagenase in serum-containing cultures. Collagenase production by JTC-12 cells was stimulated more than ten-fold with the addition of 12-0-tetradecanoyl-phorbol-13-acetate. The JTC-12 cell collagenase was purified 2,370-fold over the conditioned medium to a specific activity of 5,940 units/mg with a yield of 79% by heparin-Sepharose, ion-exchange and immunoadsorption chromatography. Thus the JTC-12 cell culture appears to be a useful model for studying the initial degradation of surrounding connective tissues by epithelial tissue in carcinogenesis.

Animals↗

[Benign osteoblastoma of the parietal bones].

Benign osteoblastoma accounts for less than 1% of the primary bone tumors and the calvarial lesion is extremely rare. There are only 12 reported cases in the literature as far as we could collect. We have presented a case of benign osteoblastoma originated from the parietal bone. This 9-year-old boy struck his head on the parietal region and noticed the bulging at the same site. A month later he visited to Fukuoka University Hospital because of persistent bulging of the same site. Neurological examinations were normal. Plain skull roentgenogram on Towne view showed radiolucent area in the midline of parietal bones with irregular margins and in tangential view the outer table revealed thinning and expanding. Coronal CT scan demonstrated same abnormality and intact inner table. The tumor was located within the dipole in the bilateral parietal bones and was removed by a simple curettage. The microscopic feature showed numerous osteoblasts, osteoblastic rimming and many multinucleated giant cells. These indicated a typical benign osteoblastoma. He has been doing well one year after the operation without any evidence of recurrence.

Child↗