Search PubMed⌕ Search

Biomedical subjects

S Sakamoto

Publications and source records attributed to S Sakamoto.

At least 469 records · Page 26Linked to original sources

Bone resorption by isolated osteoclasts in living versus devitalized bone: differences in mode and extent and the effects of human recombinant tissue inhibitor of metalloproteinases.

The incubation of isolated osteoclasts with devitalized bone has become a widely used method for the recent study of bone resorption. Although the studies employing this method have definitively demonstrated that isolated osteoclasts have an avid capacity to resorb devitalized bone, the resorption in this model appears to be different from that of living bone as observed in vivo and in organ culture studies. To evaluate how the resorption of living bone is different from that of devitalized bone, we have extended this bone resorption model using isolated osteoclasts by including both devitalized and living bone substrates. Living bone substrates were freshly prepared from calvaria of 8- to 12-month-old mice. Periosteum, cellular components, and osteoid were completely scraped off to leave a rigid, smooth, mineral-exposed surface for the isolated osteoclasts to act upon. Some of the bone pieces were devitalized by repeated freezing and thawing. Living and devitalized bones were cultured with isolated rabbit osteoclasts for 60 h with or without recombinant human tissue inhibitor of metalloproteinases (100 micrograms/ml). The extent of bone resorption was assessed by measuring both the area and the depth of resorption pits. Comparing the areas of the resorption pits showed significantly more resorption in living bone than in devitalized bone (27% of that of living bone). Recombinant human TIMP reduced the resorption of living bone by 73% but did not, however, inhibit the resorption of devitalized bone. Similarly, resorption pits formed on the living bones were significantly deeper (on the average, 12.4 microns) than those formed on the devitalized bones (on the average, 4.3 microns). The average depth of the resorption pits on living bone was significantly reduced by the presence of the inhibitor, whereas there was no difference between the control and inhibitor-treated devitalized bones. These results suggest that the mechanisms underlying the resorption of living bone and that of devitalized bone are not the same and that the resorption of living bone is aided by osteocytes.

Animals↗

Quantitative measurement of regional myocardial blood flow in patients with coronary artery disease by intravenous injection of 13N-ammonia in positron emission tomography.

Measurement of myocardial blood flow with 13N-ammonia, a technique previously employed successfully in animal experiments, was introduced into clinical use to study patients with coronary artery disease. This advance has become possible by the development of a high resolution gated scan positron emission tomographic (PET) scanner equipped with a real time decay correction mechanism, HEADTOME-IV. The information obtainable includes myocardial size and wall motion as well as the absolute quantity of blood flow in various myocardial regions. The technique is simple but requires continuous arterial blood withdrawal for calculation of the arterial input function time integral. The alternative to this technique, i.e. the computation of intra left ventricular blood pool activity by PET is also discussed.

Adult↗

Production of paralytic shellfish toxins by a bacterium Moraxella sp. isolated from Protogonyaulax tamarensis.

A bacterium Moraxella sp. isolated from Protogonyaulax tamarensis was cultured in various conditions. Changes of toxicity and toxin components of the cells during culture were analyzed by bioassay and HPLC-fluorometric analysis. Toxin productivity of Moraxella sp. increased when it was cultured in nutrition-deficient environments. The main toxins produced by Moraxella sp. in these conditions were gonyautoxins (GTXs), mainly GTX 1 and 4 which are major toxins of P. tamarensis.

Animals↗

Effect of adrenergic agonists on human chorionic gonadotropin release by human trophoblast cells obtained from first trimester placenta.

The cultured syncytiotrophoblast cells from human first trimester placenta were used to determine the effect of adrenergic agonists on human chorionic gonadotropin (hCG) production in vitro. Beta-adrenergic agonists isoproterenol, ritodrine and isoxsuprine increased the hCG release during the 2 h incubation period, however, alpha-agonists norepinephrine and phenylephrine and a beta 1-agonist dobutamine had no effect. The effect of isoproterenol was blocked by propranolol and butoxamine, but less efficiently by phentolamine and atenolol. These results indicate that placental hCG production can be modulated by stimulation of beta-, possibly beta 2-adrenoceptors but not by alpha-adrenoceptors.

Adrenergic Agonists↗

Distribution and induction of alkoxyresorufin O-dealkylases and gamma-glutamyl transpeptidase in porcine ciliary epithelium.

Nonpigmented epithelial (NPE) cells and pigmented epithelial (PE) cells were separated from porcine ciliary body by a simple surgical procedure. Using primary cultures of separated cells, basal and induced activities of 7-ethoxy resorufin (ER) O-dealkylase, 7-pentoxy resorufin (PR) O-dealkylase, and gamma-glutamyl transpeptidase (GGTP) were determined. These enzymatic activities were primarily associated with NPE cells; PE cells showed little or no activity. Treatment of NPE cells with phenobarbital for 48 hours resulted in about 5-fold increase in PR O-dealkylase activity but not ER-Odealkylase activity. Conversely, 3-methylcholanthrene treatment increased ER O-dealkylase activity 5-6 times over the basal level but had little or nor effect on PR O-dealkylase activity. The enhancement of enzymatic activities by inducers was completely inhibited by cyclohexamide. NPE cells exhibited higher GGTP activity than PE cells. Both phenobarbital and 3-methylcholanthrene augmented the GGTP activity of NPE cells but not of PE cells. The physiological significance of the regional differences in enzyme distribution was discussed.

Animals↗

Thymidine kinase and alpha-fetoprotein as biochemical markers of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene treatment in rats.

It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by such azo dye carcinogens as 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). Thymidine kinase (TK) catalyzes the formation of deoxythymidine monophosphate (dTMP) by the phosphorylation of thymidine via the salvage pathway. In the present study, we investigated serum alpha-fetoprotein (AFP) and TK levels, and tissue TK and its isozyme activities in the liver of rats treated with 3'-MeDAB. Serum TK activities rose abruptly directly after the onset of 3'-MeDAB treatment, peaking after 1 week and then gradually decreasing. At 3 weeks, though serum TK was decreasing, serum AFP and tissue TK began to increase, and oval cells appeared in the liver. At 5 weeks, though serum TK reached a nadir, serum AFP and tissue TK formed transient peaks, and oval cells occupied a major part of the hepatic lobules with hyperplastic nodules. Thereafter, serum TK continued to increase, and serum AFP and tissue TK, after transiently decreasing, re-increased; at 20 weeks, each value was at high level, and mixed type hepatocarcinoma was observed. The liver TK isozymes were separated into three types by DEAE-cellulose column chromatography. A 3'-MeDAB diet induced a remarkable increase in activity of cytosolic and fetal type isozyme in non-tumorous regions of livers at 5 weeks and tumorous regions at 20 weeks. These results indicate that early biochemical changes in 3'-MeDAB-induced hepatocarcinoma in rats may serve as a useful model and provide a valuable insight in hepatocarcinogensis.

Animals↗

Inhibitory effect of aerosol WP871 on SRS-A mediated bronchoconstriction in the guinea pig in vivo.

Slow-reacting substance of anaphylaxis (SRS-A) is an important factor mediating bronchoconstriction in asthma. We developed a guinea pig model for SRS-A mediated bronchoconstriction induced by antigen inhalation. Using this model, we investigated the effect of inhaled WP871, a new anti-allergic drug, on bronchoconstriction. Aerosol WP871 (0.01 and 0.033%) to some extent inhibited the antigen-induced bronchoconstriction in a dose-dependent fashion, but high-dose WP871 (0.1%) inhalation itself produced a non-specific bronchoconstriction. However, aerosol WP871 (0.033%) showed no inhibitory effect on bronchoconstriction caused by direct inhalation of leukotriene C4, a component of SRS-A. These findings indicate that aerosol WP871 does not antagonize SRS-A, but inhibits synthesis and/or release of SRS-A and has some non-specific bronchoconstrictive effect in high concentration.

Aerosols↗

Ultrasonographic monitoring of the placenta in patients with bleeding during the first and second trimesters.

Thirteen patients with vaginal bleeding in the first and second trimester, in 730 pregnancies confirmed with live fetuses, were diagnosed as having subchorionic hematoma at the perivillous or periplacental region by a real-time B-mode scan device. In 9 of the 13 patients, the hematoma disappeared within 1 to 3 months after detection, while in 2 patients it increased in size. Seven of the 13 pregnancies progressed to full term (53.8%), 3 ended in premature deliveries (23.1%) and 3 in spontaneous abortions (23.1%). In 5 of the 13 patients, PROM occurred. Pathological examinations revealed 5 circumvallate (38.5%) and 2 circummarginate (15.4%) placentas. Since our clinical observation indicates that subchorionic hematoma and marginal separation of the placenta may be important causes of bleeding during pregnancy, monitoring of the placenta and fetus by ultrasound was used to obtain precise information in order to manage patients with bleeding. It might be speculated that extrachorial placenta results from subchorionic hematoma or its absorption.

Adult↗

Plasma levels of insulin-like growth factor-I and its binding protein in polycystic ovary syndrome.

Patients with polycystic ovary syndrome (PCOS) had significantly higher levels of total insulin-like growth factor (IGF-I) than those in age- and weight-matched controls (PCOS, 230 +/- 21 ng/ml; control, 180 +/- 16 ng/ml; mean +/- SE, p less than 0.05) as well as free IGF-I (PCOS, 3.8 +/- 0.2 ng/ml; control, 3.0 +/- 0.2 ng/ml; p less than 0.05). These elevated levels of IGF-I were correlated slightly with levels of LH and LH/FSH ratio (r = 0.171, p less than 0.05 and r = 0.239, p less than 0.01, respectively). Elevated fasting levels of insulin and decreased levels of IGF binding protein (32K-BP) were also observed in PCOS, and the levels of 32K-BP in PCOS were negatively correlated with insulin (r = -0.39, p less than 0.01). These results suggest that elevated IGF-I levels and decreased 32K-BP levels in the circulation are one of the endocrinological features of PCOS and that insulin is responsible for the clinical manifestation of decreased 32K-BP levels in PCOS.

Adult↗

[Studies of cerebral blood flow and metabolism in patients with senile dementia of the Alzheimer's type and diagnostic evaluation of the dementing illnesses by positron emission tomography].

This study was designed to estimate cerebral dysfunction in senile dementia of the Alzheimer's type (SDAT). Regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF) and cerebral oxygen consumption (rCMRO2) were studied in 16 patients with SDAT and 5 age-matched normal elderly people by positron emission tomography (PET), using the 15O labeled CO2 and O2 inhalation technique. This technique was also applied to the evaluation of PET in diagnosing the dementing illnesses. In this study, a total of 19 pairs of bilateral cerebral regions were analyzed and the reductions of rCBF and rCMRO2 in each region were compared with those of the primary sensorimotor cortex to demonstrate any significant localized difference between each clinical stage of the SDAT and normal controls. In the mild SDAT group, CMRO2 of the temporal cortex was significantly reduced, as compared with that of controls. In the moderate SDAT group, CBF of the temporal cortex and CMRO2 of the temporal and parietal cortices were significantly reduced. In the severe SDAT group, CBF and CMRO2 of the frontal cortex were also reduced and those of the occipital cortex were relatively unchanged. This suggested that mildly demented patients showed a metabolic reduction in the temporal cortex and as the dementia progressed, metabolic reductions were extended to the parietal and frontal cortices. Reductions in blood flow were followed by further metabolic reductions. More detailed investigation of the PET images of SDAT revealed that relative oxygen hypometabolism of the posterior temporal and posterior parietal association cortices occurred in the mildly demented patients earlier than that of the other association cortices. These findings are consistent with neuropathological studies of SDAT. The right/left ratio of rCMRO2 was also analyzed in each region. The right/left oxygen metabolic asymmetry in the temporal and parietal cortices was correlated with the difference between speech and visuospatial functions. Namely, the patients with a lower metabolism in the left hemisphere had more disturbances in speech than visuospatial functions. In addition, the PET images of SDAT were compared with those of multi-infarct dementia (MID) and Pick disease. In patients with MID, there were reductions of CBF and CMRO2 unhomogenously all over association cortices, but the reductions were most remarkable in the frontal cortex. Patients with Pick disease showed diffuse lobar reductions of CBF and CMRO2 in the frontal and temporal cortices.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Attenuating effect of a thromboxane synthetase inhibitor (OKY-046) on bronchial responsiveness to methacholine is specific to bronchial asthma.

To determine whether the involvement of thromboxane A2 in bronchial hyperresponsiveness (BHR) is specific to asthma, we examined the effects of a selective inhibitor of thromboxane synthetase (OKY-046) and a cyclooxygenase inhibitor (indomethacin) on bronchial responsiveness to methacholine in normal subjects and patients with chronic bronchitis, diffuse bronchiectasis, and intrinsic bronchial asthma. The provocative concentration of methacholine producing a 20 percent fall in forced expiratory volume in 1 s (PC20-FEV1) was measured before and after oral administration of OKY-046 (2,600 mg over four days) and indomethacin (450 mg over three days) in ten normal, ten bronchitic, nine bronchiectatic, and eight asthmatic subjects, respectively. Baseline values of FEV1 and forced vital capacity (FVC) were not altered by OKY-046 or indomethacin. The geometric mean value of PC20-FEV1 increased significantly (p less than 0.005) from 1.78 to 4.27 mg/ml after OKY-046 in asthmatic subjects, but not in normal, bronchitic, or bronchiectatic subjects. On the other hand, PC20-FEV1 increased significantly (p less than 0.005) from 2.19 to 8.13 mg/ml after indomethacin in bronchiectatic subjects, but not in normal, bronchitic, or asthmatic subjects. We conclude that the involvement of thromboxane A2 in BHR may be specific to asthma, and bronchial responsiveness of bronchiectasis may be potentiated by inflammatory release of bronchoconstrictor prostaglandins except for thromboxane A2. Further studies using thromboxane A2 receptor antagonists are needed to confirm the conclusion.

Acrylates↗

[Clinical study of rhG-CSF (KRN8601) in patients with myelodysplastic syndrome].

A clinical study of rhG-CSF (KRN8601) in patients with myelodysplastic syndrome (MDS) was performed to investigate the hematopoietic effects and the increase of neutrophils. The rhG-CSF was administered daily by intravenous infusion over 30 min. to 21 patients with MDS (PARA = 11, RAEB = 4, RAEB in T = 6). The dose was escalated stepwise from 50 to 400 microgram/m2 every week. Within one week to 26 days after commencement of rhG-CSF administration, the increases of absolute neutrophil counts in peripheral blood were observed in all patients. Treatment with rhG-CSF enhanced normal marrow myeloid cell differentiation and maturation in 3 of 9 PARA patients and in 3 of 4 RAEB patients. None of patients changed to acute leukemia attributable to rhG-CSF, but one of RAEB patient and two of RAEB in T patients progressed to leukemic phase in 21 days or two months after treatment. Minor side effects or abnormal laboratory findings were observed in 3 patients (14.3%). These results suggested that treatment with rhG-CSF was well tolerated and effective for improving the neutropenia between 50 to 400 micrograms/m2 in patients with MDS.

Adult↗

[Cerebral blood flow and cerebral oxygen metabolism in patients with dementia of frontal lobe type].

This study was designed to investigate the differences in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) between patients with dementia of frontal lobe type and patients with Alzheimer's disease. Positron emission tomography (PET) using 15O steady state inhalation technique was carried out in 5 patients with a clinical diagnosis of dementia of frontal lobe type and 7 patients with a clinical diagnosis of Alzheimer's disease. CBF and CMRO2 were significantly decreased in the frontal cortex except for precentral region in patients with dementia of frontal lobe type in comparison to those values in patients with Alzheimer's disease. However, in patients with dementia of frontal lobe type CBF and CMRO2 in the parietal cortex and the occipital cortex were relatively preserved when compared with patients with Alzheimer's disease. In comparison with values for CBF and CMRO2 in the posterior part of brain [frontal or temporal/(parietal + occipital)/2 ratio], both values in the frontal cortex were markedly decreased in all 5 patients with dementia of frontal lobe type, but there was no marked reduction in the frontal cortex in patients with Alzheimer's disease. In addition, in 2 patients with dementia of frontal lobe type whose duration of the disease was more than 7 years, CBF and CMRO2 in the temporal cortex were markedly reduced in comparison with values in the posterior part of brain. These results suggested that PET findings of marked reduction in CBF and CMRO2 in the frontal cortex are useful to distinguish dementia of frontal lobe type from Alzheimer's disease.

Adult↗

[Significance of HDL cholesterol/apolipoprotein A-I ratio].

HDL cholesterol (HDL-Ch)/apolipoprotein A-I (A-I) ratio was studied in fourteen healthy students, fifteen male habitual drinkers, five male patients with chronic hepatitis (CH) and seven controls. HDL-Ch/A-I ratio in male students, female students, male drinkers, CH and control were 0.36 +/- 0.029, 0.39 +/- 0.03, 0.41 +/- 0.065, 0.40 +/- 0.02, and 0.36 +/- 0.039, respectively. Elevation of HDL-Ch/A-I ratio in female students, male drinkers and CH were statistically significant compared with control, while there was no significant change in HDL-Ch or A-I in female students but the elevations of both in male drinkers or the reduction of A-I in CH. Positive correlations were found between HDL-Ch/A-I ratio and HDL2-Ch, and HDL2-Ch/HDL3-Ch ratio in students and CH. The elevation of HDL-Ch/A-I ratio in CH appeared to be related to the reduction of HDL3-Ch. It is suggested that HDL-Ch/A-I ratio could indicate HDL2-Ch/HDL3-Ch ratio and is useful parameter for analysis of HDL metabolism.

Adult↗

[Noninvasive estimation of max (dP/dt) of the left ventricle based on maximum aortic flow acceleration as measured by pulsed Doppler echocardiography].

To obtain an index of left ventricular contractility, cardiac catheterization is necessary. In the present study, we ascertained whether max(dP/dt) could be obtained noninvasively in vivo based on the theoretical equation, max(dP/dt) not equal to rho cmax(du/dt), where rho is the density of blood, c is the pulse wave velocity of the aorta and max(du/dt) is the maximum acceleration of the aortic blood flow. This equation is based on the theory of pulse wave propagation, and was established in animal experiments. We further attempted to clarify the clinical usefulness of rho cmax(du/dt) by examining the effects of afterload and preload on rho cmax(du/dt). Twenty-seven patients without stenosis of their aortic valves and left ventricular outflow tracts were observed. During cardiac catheterization, we measured max(dP/dt) using a catheter-tip micromanometer, max (du/dt) using pulsed Doppler echocardiography and pulse wave velocity by simultaneously recording the femoral pulse wave and the carotid pulse wave. The measurements were performed at rest, before and after an increase in contractility with dobutamine administration, an increase in afterload with methoxamine administration and an increase in preload by leg elevation. There was good linear correlation (Y = 0.95X + 7.51, r = 0.84, p less than 0.0005) between max(dP/dt)[X] and rho cmax(du/dt)[Y] at rest. When the contractility was changed, rho cmax(du/dt) reflected changing of max(dP/dt). Moreover, when the afterload and preload were increased, the changing pattern of rho cmax(du/dt) was similar to that of max(dP/dt). Max(du/dt), index of cardiac performance previously proposed, showed a different changing pattern than max(dP/dt), indicating that max(du/dt) was influenced substantially by loading conditions. These results indicated that we can obtain max(dP/dt) noninvasively and reliably by measuring rho cmax(du/dt).

Aged↗

Liver abscess complicating intratumoral ethanol injection therapy for HCC.

We report a patient who developed multiple liver abscesses and sepsis caused by lactobacilli after the percutaneous intratumoral injection of ethanol for hepatocellular carcinoma. We diagnosed the liver abscess at an early stage because of a the finding of gas on ultrasound and computed tomography. Blood cultures grew Gram-positive rods, which were of the Lactobacillus species. The patient responded to the administration of antibiotics, and his hepatic tumors have not recurred in the 7 months since treatment. This is the first report of liver abscess following percutaneous ethanol injection therapy.

Aged↗

[A new method of preparation of doxorubicin-in-oil suspension using ultrasonificator attached with Cuphorn].

The property of selective deposition of oily contrast medium, Lipiodol (LPD), in tumor tissue was utilized for targetting intraarterial infusion chemotherapy for hepatic cancers. For this therapy anti-cancer agents need to be suspended in LPD. In this report the new suspension device using ultrasonificator attached with Cuphorn was studied. Doxorubicin (Dx) was stable to ultrasonification for 1 hour. Ten mg/ml of Dx was mixed with LPD and this mixture was treated 2 times for 5 minutes with the ultrasonification method. This procedure was simple and sterile, as the commercially used Dx vials into which LPD was injected were set in the Cuphorn and ultrasonificated just as sealed. Microscopic examination of the suspension showed uniform dispersion of Dx particles without formation of aggregates. Dx particles were finely and regularly fragmented. In vitro the suspensions showed a gradual release of Dx from LPD to water phase. In one case with hepatocellular carcinoma received intraarterial infusion of this suspension, the size of the tumor and serum level of alpha-fetoprotein was prominently decreased. This ultrasonification method was simple and convenient to prepare Dx-in-oil suspension.

Carcinoma, Hepatocellular↗