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Biomedical subjects

T Sakuma

Publications and source records attributed to T Sakuma.

At least 163 records · Page 9Linked to original sources

Influence of reduced presynaptic myocardial norepinephrine stores on left ventricular contractility.

Many investigators have reported that myocardial norepinephrine content is decreased in congestive heart failure. However there have been no studies of how decrease in myocardial norepinephrine might influence myocardial contraction. To clarify whether decreased myocardial norepinephrine per se affects myocardial contraction, we observed the change in left ventricular contractility during 30 min of left stellate ganglion stimulation in control and acutely reserpinized dogs. We obtained left ventricular max dp/dt and left ventricular end-systolic pressure-segment length relationships as indicators of left ventricular contractility. Both parameters decreased after left stellate ganglion stimulation in reserpinized dogs (left ventricular max dp/dt: 2064 +/- 200 to 1608 +/- 168 mmHg/s, left ventricular end-systolic pressure-segment length slope 117 +/- 22 to 79 +/- 14 mmHg/mm, n = 8, P less than 0.05), while they did not change in controls. In reserpinized dogs, left ventricular norepinephrine content decreased to one-third that of controls before the stimulation, and further decreased after stimulation. These data indicate that lowered myocardial norepinephrine itself may be responsible for the negative effect on left ventricular contractility in congestive heart failure.

Animals↗

Analysis of acylcarnitines in maternal urine for prenatal diagnosis of glutaric aciduria type 2.

The urinary acylcarnitine profiles of two mothers whose first children were diagnosed to have glutaric aciduria type 2 (multiple acyl-CoA dehydrogenation deficiency, electron transfer flavoprotein (ETF) deficiency) were analysed in the second pregnancy. Large volumes of tigrylcarnitine and isovalerylcarnitine and a little glutarylcarnitine were detected. Each fetus was also diagnosed to be abnormal by enzyme activity and immunoassay of ETF protein. The acylcarnitines in the mothers' urine disappeared in 1 week after labour or artificial abortion. Acylcarnitines were never detected in the urine of controls.

Abortion, Induced↗

Antiviral activity of oxetanocins against varicella-zoster virus.

Several new nucleosides with an oxetanosyl-N-glycoside group, named oxetanocins, were evaluated for their antiviral activities against varicella-zoster virus (VZV) in human embryo lung cells. 9-(2-deoxy-2-hydroxy-methyl-beta-D-erythro-oxetanosyl)guanine (OXT-G) and 9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanosyl)-2- aminoadenine were effective against not only thymidine kinase-positive (TK+) VZV (YS strain) but also thymidine kinase-negative (TK-) VZV (YSR strain), whereas carbocyclic OXT-G was effective against TK+ VZV but not against TK- VZV. [3H]OXT-G was incorporated into TK+ VZV-infected cells and TK- VZV-infected cells more than into mock-infected cells and was converted into the triphosphate form.

Adenine↗

Alteration of urinary carnitine profile induced by benzoate administration.

To study the effect of sodium benzoate on carnitine metabolism, the acylcarnitine profile in the urine of five normal volunteers and two patients with urea cycle disorders was examined with fast atom bombardment-mass spectrometry. The volunteer subjects were given 5 g of sodium benzoate orally and the two patients with urea cycle disorders (carbamyl phosphate synthetase deficiency type I and ornithine transcarbamylase deficiency) were already undergoing treatment with sodium benzoate and L-carnitine. The amount of benzoylcarnitine excretion depended on the dose of both sodium benzoate and L-carnitine in a reciprocal relation. Increased excretions of acetylcarnitine and propionylcarnitine were also noted after sodium benzoate administration. The alteration of the urinary aclycarnitine profile was consistent with the change of mitochondrial CoA profile predicted by in vitro studies of an animal model. It is suggested that urinary acylcarnitine analysis is important to assess the effect of benzoate administration on mitochondrial function in vivo. Supplementation with carnitine may be necessary to minimise the adverse effects of sodium benzoate treatment in hyperammonaemia.

Acetylcarnitine↗

Responses of atrium and ventricle to sustained sympathetic nerve stimulation.

To determine whether chronotropic and atrial inotropic responses to sympathetic nerve stimulation are maintained longer than ventricular inotropic response, the present study was performed with control and acute reserpinized dogs. We stimulated the right stellate ganglion of both groups supramaximally for 60 min and compared right atrial responses (chronotropism and inotropism) with left ventricular (LV) dP/dtmax. In the control group, heart rate (HR) immediately increased and was only slightly attenuated with 60 min of stimulation, and right atrial (RA) inotropic response was less attenuated than was LV response (7% in HR, 33% in RA dP/dtmax, 50% in LV dP/dtmax, P less than 0.01, from the peak value of each response). RA and LV norepinephrine (NE) content was decreased by the stimulation but remained higher than the LV control value. In the reserpinized group, NE content in the RA was low before the stimulation and was further decreased by the stimulation. In this group, HR response was attenuated (27% in HR, P less than 0.01) as was LV dP/dtmax, and the difference in contractile responsiveness between atrium and ventricle disappeared (58% in RA dP/dtmax vs. 61% in LV dP/dtmax, NS). The results indicate that the chronotropic response was only slightly attenuated and that the atrial contractile response was attenuated less than the ventricular response, with sustained sympathetic nerve stimulation in the normal heart. This can be ascribed to the much higher NE content in the RA than that in the LV.

Animals↗

Alveolar and lung liquid clearance in anesthetized rabbits.

Alveolar and lung liquid clearance were studied over 8 h in intact anesthetized ventilated rabbits by instillation of either isosmolar Ringer lactate (2 ml/kg) or autologous plasma (2 or 3 ml/kg) into one lower lobe. The half time for lung liquid clearance of the isosmolar Ringer lactate was 3.3 h and that for plasma clearance was 6 h. In the plasma experiments, the alveolar protein concentration after 1 h was 5.2 +/- 0.8 g/dl, which was significantly greater than the initial instilled protein concentration of 4.3 +/- 0.7 g/dl (P less than 0.05). Thus alveolar protein concentration increased by 21 +/- 12% over 1 h, which matched clearance from the entire lung of 19 +/- 11% of the instilled volume. Overall the rate of alveolar and lung liquid clearance in rabbits was significantly faster than in prior studies in dogs and sheep. The fast alveolar liquid clearance rate in rabbits was not due to higher endogenous catecholamine release, because intravenous and alveolar (5 x 10(-5) M) propranolol did not slow the clearance. Also, beta-adrenergic therapy with alveolar terbutaline (10(-5) or 10(-4) M) did not increase the alveolar or lung liquid clearance rates. Phloridzin (10(-3) M) did not slow alveolar liquid clearance. However, amiloride (10(-4) M) inhibited 75% of the basal alveolar liquid clearance in rabbits, thus providing evidence that alveolar liquid clearance in rabbits depends primarily on sodium-dependent transport. This rabbit study provides further evidence for important species differences in the basal rates of alveolar liquid and solute clearance as well as the response to beta-adrenergic agonists and ion transport inhibitors.

Amiloride↗

[Tissue repair of uterine cervix--cell-biological properties of normal uterine cervical epithelia of transformation zone in vitro].

The objective of this study is to culture the epithelia of the transformation zone of the uterine cervix for long term and evaluate their biological characteristics, such as morphology, growth behavior, alkaline phosphatase activity and heterotransplantability. The epithelia of transformation zone of 15 cases of myoma uteri were cut into 1 x 1 x 1 mm fragments and placed directly on the cover glass. The explants were cultured at 37 degrees C in 5% CO2 and 95% air. In vitro outgrowth of squamous cells (squamous cell outgrowth pattern) was observed in 44, that of columnar cells (columnar cell outgrowth pattern) was observed 49, a mixture of squamous and columnar cell outgrowth patterns was 52 out of 198 explants of transformation zone. The squamous cells were polygonal in shape and showed a pavement-like cell arrangement. The glandular cells grew in whorled fashion. Along the margins of the outgrowth of glandular cells, two types of cells were seen after 2 weeks of culture. One type contained secretory vacuoles of glandular cell, and the other type contained a large number of tonofilaments of squamous metaplastic cells. These phenomena suggested that biological characteristics of the cells in vivo can well be retained in vitro for a relative long term (about 6 weeks).

Adult↗

[Coronary vasospastic activity at sites of percutaneous transluminal coronary angioplasty: evaluation using intracoronary acetylcholine administration].

To investigate coronary vasospastic activity after percutaneous transluminal coronary angioplasty (PTCA), we performed intracoronary injection of acetylcholine in 55 patients, mean 3.3 months after successful PTCA. Coronary spasm was defined as transient total or subtotal occlusion of the PTCA sites. Sixty-nine lesions of the 55 patients were examined to determine whether spasm was provoked by incremental doses of acetylcholine. Restenosis was defined as coronary luminal narrowing of > or = 50% after nitroglycerin or isosorbide dinitrate. Twenty of the 55 patients (36%) and 23 of the 69 lesions (33%) had coronary spasm. There was no correlation between the incidence of coronary spasm and the interval from PTCA to the acetylcholine test. The spasm was provoked in 17 lesions of the 50 non-restenotic lesions (34%) and was also provoked in 6 of the 19 restenotic lesions (32%). On the other hand, restenoses occurred in 6 of the 23 spastic lesions (26%) and in 13 of the 43 non-spastic lesions (28%). There was no correlation between the incidence of coronary spasm and the occurrence of restenoses. Twenty-four patients had undergone acetylcholine provocative test before PTCA. Among these 24 patients, 11 had coronary spasm before PTCA, and 7 had coronary spasticity after PTCA. Four patients who had positive evidence of coronary spasm before PTCA did not show negative spasm after PTCA. On the other hand, 3 patients who did not show evidence of coronary spasm showed positive evidence of coronary spasm after PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

[Time-course of the concentration of cefotiam in human extra-vascular pulmonary tissue].

The concentration of cefotiam in the blood and in blood-free, extra-vascular pulmonary tissue (lung tissue) was determined and its transition into the lung tissue was observed. One gram of cefotiam was injected intravenously into 27 lobectomized cases of bronchogenic carcinoma at 30 (n = 8), 60 (n = 6), 120 (n = 7) and 180 minutes (n = 6) before thoracotomy. Informed consent was obtained from these patients before the study. Lung samples were collected from the resected lobe immediately after thoracotomy, and the blood samples were also collected. Drug concentrations of the lung and blood specimens were determined. The blood volume of the lung sample was determined according to the gravimetric method with hemoglobin as an index. The drug concentration in the lung tissue was determined by the difference of the concentration between blood and lung. The time-courses of lung tissue drug concentration and blood drug concentration were compared. The lung tissue drug concentration reached a peak at 30 minutes after intravenous injection and thereafter decreased gradually, reaching equilibrium at about 50% of the blood concentration. Thirty minutes after intravenous injection, the lung tissue drug concentration was higher than the blood concentration, suggesting a higher rate of transition of the drug from the blood to the lung tissue than vice versa.

Biological Availability↗

[Clinical significance of serum sialyl Tn antigen in patients with gynecological cancer. STN Study Group].

Serum sialyl Tn antigen was assayed in gynecological cancer and benign patients by means of "STN OTSUKA" kits. Fifty-eight of 140 (41.1%) ovarian cancer patients showed a significant elevation of sialyl Tn antigen in serum above the cut-off level of 45 unit/ml (mean +2SD) determined from normal controls. There was no feature of positive frequency in tissue type, including serious carcinoma (47.6%), mucinous carcinoma (45.5%), clear cell carcinoma (30.4%) and endometrioid carcinoma (55.6%), but the positive frequency of mucinous carcinoma (36.8%) was higher than that of serous carcinoma (11.1%) in stage I. Compared with other markers, sialyl Tn antigen showed a very much lower false-positive rate (3.6%) in benign gynecological diseases. In the diagnosis of ovarian cancers, the combination assay of sialyl Tn antigen and CA 125 increased diagnostic efficiency compared with any other combination assays. Therefore, sialyl Tn antigen will be a useful tumor marker for ovarian cancers.

Antigens, Neoplasm↗

Movement of vesicles in cytoplasmic streaming in plasmodium.

The moving velocities of vesicles in the cytoplasmic streaming of a slime mold were measured, in which all of the vesicles passing through a designated window were counted. Vesicles in the streaming are distributed in their moving velocities and the distribution itself varies with time. The mean velocity of vesicles and its standard deviation were found to exhibit a linear relationship, suggesting a possibility that vesicles in the cytoplasm would also be involved in force generation.

Cytoplasmic Streaming↗

Cancer-associated galactosyltransferase as a new tumor marker for ovarian clear cell carcinoma.

Serum cancer-associated galactosyltransferase antigen (caGT) was assayed in gynecological cancer patients by means of a GT-II-reactive monoclonal antibody (MAb 3872)-based immunoassay. Thirty-six of 47 (75%) ovarian cancer patients showed a significant elevation of caGT in serum above the cutoff level of 200 milliunits/ml (mean +/- 2 SD) determined from normal controls. Particularly, serum caGT levels in eight of nine patients with ovarian clear cell carcinoma were above the cutoff value, and six of them gave more than 200 milliunits/ml. Elevation of caGT in serum from pregnant women was also detected, and the level increased during the course of gestation. Immunohistochemical study revealed that not only various ovarian carcinoma cells in vivo and in vitro, but also syncytiotrophoblast of early gestational placenta, fetal tissues such as mucus-producing cells in the lower alimentary tract, and renal tubules at the 11th week of gestation were stained with MAb 3872, thus indicating its oncofetal character. Compared with CA-125, caGT showed a lower false-positive rate (10%) in benign gynecological diseases, and there was no correlation between caGT and CA-125 values. Therefore, caGT will be a useful tumor marker for ovarian cancers, especially for clear cell carcinoma.

Adenocarcinoma↗

Evaluation of the susceptibility effect on the phase images of a simple gradient echo.

The phase shifts of a simple gradient echo (fast low-angle shot) were correlated with the local change in resonance frequency due to the differences in susceptibility among tissues (susceptibility effect). Susceptibility effects were considered theoretically, and the phase shifts for spherical and cylindrical configurations were calculated. A 1.5-T magnetic resonance unit and phantoms filled with solutions of copper chloride in water were used to obtain the phase images. The phase shifts of the simple gradient echo coincided with the values calculated with use of the sum of the macroscopic magnetic field and the cavity field of Lorentz. The authors conclude that the gap of the phase shifts at interfaces of tissues is useful in the evaluation of differences in magnetic susceptibility among tissues.

Cerebral Hemorrhage↗

Effects of prolonged nitrous oxide exposure on hemopoietic stem cells in splenectomized mice.

We have demonstrated in previous papers that prolonged nitrous oxide exposure suppresses murine hemopoiesis more in the spleen than in the bone marrow and that this is caused by the suppression of the hemopoietic supportive activity of the microenvironment. In the present study, we used splenectomized mice as an experimental model to investigate the direct effect on bone marrow function of prolonged nitrous oxide inhalation. All of the experimental mice were splenectomized at the age of 4 wk. Half of the experimental mice were continuously exposed to 50% nitrous oxide, and the remainder were continuously exposed to air as controls, starting 3 wk after splenectomy and lasting 14 days, and the numbers of pluripotent hemopoietic stem cells (CFU-S) and granulocyte-macrophage progenitor cells (GM-CFC) in bone marrow were counted. The numbers of pluripotent hemopoietic stem cells and granulocyte-macrophage progenitor cells in the bone marrow of mice exposed to air showed no significant change. The numbers of these two types of cells found in nitrous oxide-exposed mice were approximately 60% of control levels. These data are almost the same as our previously reported bone marrow data obtained in nonsplenectomized mice exposed to nitrous oxide for 14 days. The present results suggest that the marked decrease in the number of splenic hemopoietic stem cells in our previous data is not a result of migration of the cells to bone marrow, and that nitrous oxide directly affects murine bone marrow hemopoiesis.

Animals↗

[Biological properties of two newly established cell lines (RMUG-S, RMUG-L) from a human ovarian mucinous cystadenocarcinoma].

Two morphological different cell lines (RMUG-S and RMUG-L) have been established from a human ovarian mucinous cystadenocarcinoma. CA-125 and CEA were demonstrated in the patient's serum. PAS, Alcian blue and mucicarmine positive substances were observed in the original tumor and two cultured cells. The modal chromosomal numbers of RMUG-S and RMUG-L were stable in the hypodiploid and hyper-triploid ranges, respectively. Radioimmunoassay and immunocytochemical staining revealed that RMUG-S and RMUG-L mainly produced CA-125 and CEA, respectively. In CBA nude mouse, RMUG-S and RMUG-L cells mainly produced poorly-differentiated adenocarcinoma, but in mucinous cystadenocarcinoma was detected in part of the RMUG-L tumor.

Animals↗

[Denervated myocardium detected by I-123 metaiodobenzylguanidine myocardial imaging following successful percutaneous transluminal coronary thrombolysis].

I-123 metaiodobenzylguanidine (MIBG) is taken up by sympathetic nerve endings. Thirteen patients with acute myocardial infarction, in whom reperfusion was achieved with percutaneous transluminal coronary thrombolysis (PTCR), MIBG and Tl-201 (Tl) images 14 days after PTCR which were simultaneously performed were studied. In the late stage, Tl myocardial stress test was also performed to detect ischemia. The extent of myocardial defect was estimated as percent defect. Wall motion was assessed by echocardiography. Ejection fraction (EF) was assessed in the chronic phase using left ventriculography. In nine of the 13 patients, the denerved myocardial regions having the MIBG defects were noted using a Tl uptake. A percent defect noted in MIBG images was 25 +/- 6% and was greater than those (6 +/- 6%,p less than 0.01) in Tl images. During the convalescent phase, the wall motion of the denerved region was restored (2, normal; 4, mild hypokinesis; 3, moderate hypokinesis) and in the chronic phase, EF was well preserved (61 +/- 14%). Ischemic regions noted in stress images coincided with denerved regions. In four patients without the denerved myocardium, EF was 46 +/- 3% (p less than 0.05) and wall motion of defect areas was akinetic. Both EF and myocardial viability were more preserved in cases with denerved region; i.e., PTCR was successfully performed in these cases. It was suggested that the denerved region was the area of severe ischemia during the acute phase and that it was salvaged by PTCR. The sympathetic nerve was damaged by severe ischemia, and depressed sympathetic function persisted long after the recovery of both myocardial perfusion and the wall motion.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗