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Biomedical subjects

S Nemoto

Publications and source records attributed to S Nemoto.

At least 37 records · Page 2Linked to original sources
PubMed2000

Role for mitochondrial oxidants as regulators of cellular metabolism.

Leakage of mitochondrial oxidants contributes to a variety of harmful conditions ranging from neurodegenerative diseases to cellular senescence. We describe here, however, a physiological and heretofore unrecognized role for mitochondrial oxidant release. Mitochondrial metabolism of pyruvate is demonstrated to activate the c-Jun N-terminal kinase (JNK). This metabolite-induced rise in cytosolic JNK1 activity is shown to be triggered by increased release of mitochondrial H(2)O(2). We further demonstrate that in turn, the redox-dependent activation of JNK1 feeds back and inhibits the activity of the metabolic enzymes glycogen synthase kinase 3beta and glycogen synthase. As such, these results demonstrate a novel metabolic regulatory pathway activated by mitochondrial oxidants. In addition, they suggest that although chronic oxidant production may have deleterious effects, mitochondrial oxidants can also function acutely as signaling molecules to provide communication between the mitochondria and the cytosol.

3T3 Cells↗
PubMed2000

Differential effects of pressure or volume overload on myocardial MMP levels and inhibitory control.

Left ventricular (LV) pressure (PO) or volume (VO) overload is accompanied by myocardial remodeling, but mechanisms that contribute to this progressive remodeling process remain unclear. The matrix metalloproteinases (MMPs) contribute to tissue remodeling in a number of disease states. This study tested the hypothesis that increased MMP expression and activity occur after the induction of an LV overload, which is accompanied by a loss of endogenous MMP inhibitory control. LV MMP zymographic activity and species abundance were measured in dogs under the following conditions: acute PO induced by ascending aortic balloon inflation (6 h, n = 9), prolonged PO by aortic banding (10 days, n = 5), acute VO through mitral regurgitation secondary to chordal rupture (6 h, n = 6), prolonged VO due to mitral regurgitation (14 days, n = 7), and sham controls (n = 11). MMP zymographic activity in the 92-kDa region, indicative of MMP-9 activity, increased over threefold in acute PO and VO and fell to control levels in prolonged PO and VO. The MMP-9 activity-to-abundance ratio increased by over fourfold with acute VO and twofold in acute PO, suggesting a loss of inhibitory control. Endogenous MMP inhibitor content was unchanged with either PO or VO. Interstitial collagenase (MMP-1) content decreased by 50% with acute VO but not with acute PO. Stromelysin (MMP-3) levels increased by 40% with acute VO and increased by 80% with prolonged PO. Although changes in LV myocardial MMP activity and inhibitory control occurred in both acute and prolonged PO and VO states, these changes were not identical. These results suggest that the type of overload stimulus may selectively influence myocardial MMP activity and expression, which in turn would affect the overall LV myocardial remodeling process in LV overload.

Animals↗
PubMed2000

Effect of high amniotic fluid pressure on fetal circulation.

The purpose of this study was to investigate the effects of high amniotic fluid pressure (AFP) created by amnioinfusion on fetal circulation. Five pregnant goats whose fetuses had a mean gestational age of 131 +/- 2 days (term 145 days) were used. After a 30 minute control period, 1500 ml of warm saline was infused to the amniotic cavity over a period of 30 minutes. The AFP gradually increased during amnioinfusion and remained 2-3 mmHg above the control level for 3 hours after amnioinfusion. Fetal arterial pH (FpH) tended to decrease, and there was a significant negative correlation between the FpH and AFP (r = -0.723). Fetal arterial pO2 also tended to decrease and negatively correlated to the AFP (r = -0.59). On the other hand, fetal arterial pCO2 tended to increase and positively correlated with the AFP (r = 0.75). Although amnioinfusion is useful for improving the status of a distressed fetus, the fetal condition may be jeopardized at the same time. Therefore, careful monitoring of the AFP and fetal status is recommended during amnioinfusion.

Amniotic Fluid↗
PubMed2000

[Successful treatment using detachable coils for traumatic carotid cavernous fistula as a complication of transsphenoidal surgery for a pituitary adenoma: a case report].

We report a case of a patient with traumatic carotid cavernous fistula (CCF) caused by transnasal-transsphenoidal surgery, who was successfully treated using detachable coils. A 47-year-old man was admitted to our hospital because of severe headache. He was confirmed to have a nonfunctioning pituitary adenoma with presellar-type sphenoid sinus. Cerebral angiography initially disclosed no vascular lesions. A transnasal-transsphenoidal adenomectomy was performed. When the anterior wall of the sphenoid sinus was dissected with a chisel, the chisel deeply stuck into the posterolateral part of the sinus. Profuse arterial bleeding was observed through the sphenoid sinus. The bleeding was stopped easily by compression and packing with bone wax. The operation was continued, the sellar floor was opened widely and the tumor was removed subtotally. The medial wall of the cavernous sinus was intact. Histological examination revealed a pituitary adenoma. Immediately after surgery, the patient noticed a bruit. He developed chemosis and abducent palsy on the right side. Cerebral angiography displayed a high-flow CCF, which was attributed to the carotid artery injury caused by the transnasal-transsphenoidal surgery. The CCF disappeared after two-staged embolization using detachable coils, 1st transvenous and 2nd transarterial. Ten months later, cerebral angiography showed persistent occlusion of the fistula, and the patient experienced no tumor recurrence. It is suggested that drilling is a safer procedure than using a chisel for dissection of a sphenoid sinus with incomplete pneumatization. Endovascular treatment using detachable coils proved useful to manage the CCF, an unusual complication of transsphenoidal surgery.

Adenoma↗
PubMed2000

Phase I trial of oral 2'-deoxy-2'-methylidenecytidine: on a daily x 14-day schedule.

2'-deoxy-2'-methylidenecytidine (DMDC) is a potent deoxycytidine analogue. Preclinical studies of DMDC demonstrated activity against a variety of murine and human tumors in cell cultures and murine models and indicate enhanced antitumor activity of DMDC when it was administered in a manner that provided prolonged systemic exposure. In view of this observation, this study was designed to determine the toxicities, maximum-tolerated dose, and pharmacokinetic profile of DMDC. DMDC was given p.o. under fasting conditions for 14 consecutive days every 4 weeks in patients with advanced solid tumors. The starting dose was 12 mg/m2/day. Pharmacokinetic studies were carried out on days 1 and 14 of the first cycle. Fourteen patients received 22 courses of DMDC. The dose-limiting toxicities were anorexia, leukopenia, thrombocytopenia, and anemia. General fatigue was the common nonhematological toxicity. The maximum-tolerated dose was 18 mg/m2/day, at which two of six patients developed grade 3 toxicities. This dose level could also be considered for Phase II testing with this schedule. At the 18-mg/m2/day dose level, the mean terminal half-life, maximum plasma concentration (Cmax), the area under the plasma drug concentration-time curve (AUC(0-infinity)) on day 1 were 1.7496 h, 112.9 ng/ml, and 399.8 ng x h/ml, respectively. Forty to 50% of the administered dose was recovered in the urine, indicating a good bioavailability and resulting significant systemic exposure to the drug, which may enable chronic oral treatment.

Adenocarcinoma↗
PubMed2000

Effects of aging on EMG variables during fatiguing isometric contractions.

The purpose of this study was to evaluate the neuromuscular adaptation that occurred with aging, by comparing young and aged subjects with respect to changes in surface EMG from the tibialis anterior muscle during fatiguing contractions. EMG variables such as the averaged rectified value (ARV), median frequency (MDF), and muscle fiber conduction velocity (MFCV) were calculated during maximal (MVC, 3 sec) and submaximal (60% MVC, 60 sec) isometric contractions. Muscular force, ARV, MDF, and MFCV during MVC were significantly greater in the young than in the elderly (p < 0.05). EMG amplitude increased and the waveform slowed in all subjects during submaximal contractions, indicating the development of local muscle fatigue. As fatigue progressed, the ARV increased and the MDF and MFCV decreased significantly (p < 0.01). The fatigue-induced changes in the MDF and MFCV were significantly smaller in aged than in young subjects (p < 0.05), a trend also seen in the ARV change, which means that the elderly cannot be fatigued as much as the young with contractions of the same relative intensity. These results as a whole suggest that the aged subjects hold an adaptive motor strategy to cope with age-related neuromuscular deteriorations, due to the decline of motor unit activation and selective atrophy of fast twitch muscle fibers.

Adult↗
PubMed1999

Dorsum sellae meningioma mimicking pituitary macroadenoma: case report.

BACKGROUND: A dorsum sellae meningioma is a rare occurrence. It is difficult to evaluate dorsum sellae meningiomas preoperatively from the viewpoint of neuroimaging. We report a rare case of dorsum sellae meningioma mimicking pituitary macroadenoma in a 73-year-old woman. CASE PRESENTATION: The patient presented with bitemporal hemianopsia and panhypopituitarism. Magnetic resonance imaging demonstrated a bright, homogeneously enhancing intra- and suprasellar mass and a hypointense region in this mass, which was interpreted as a dorsum sellae. Transsphenoidal extirpation was used because of a suspicion of nonsecreting pituitary macroadenoma. Histopathologically, the tumor was diagnosed as a meningioma. Superselective external carotid angiography before the second surgery revealed that the mass was supplied by the left accessory middle meningeal artery and appeared to originate from dorsum sellae. After preoperative embolization, the patient developed hyponatremia. The tumor was subtotally removed via a transcranial route, and the attachment to the dorsum sellae was coagulated extensively. She did well after a second surgical procedure. CONCLUSION: These radiologic findings may be useful in differentiating dorsum sellae meningioma from pituitary macroadenoma.

Adenoma↗
PubMed1999

Translational mechanisms accelerate the rate of protein synthesis during canine pressure-overload hypertrophy.

This study examined how translational mechanisms regulate the rate of cardiac protein synthesis during canine pressure overload in vivo. Acute aortic stenosis (AS) was produced by inflating a balloon catheter in the ascending aorta for 6 h; sustained AS was created by controlled banding of the ascending aorta. AS caused significant hypertrophy as reflected by increased left ventricular (LV) mass after 5 and 10 days. To monitor LV protein synthesis in vivo, myosin heavy chain (MHC) synthesis was measured by continuous infusion of radiolabeled leucine. Acute AS accelerated the rate of myosin synthesis without a corresponding increase in ribosomal RNA, indicating an increase in translational efficiency. Total MHC synthesis (mg MHC/LV per day) was significantly increased at 5 and 10 days of sustained AS. Total MHC degradation was not significantly altered at 5 days of AS but increased at 10 days of AS in concordance with a new steady state with respect to growth. Translational capacity (mg total RNA/LV) was significantly increased after 5 and 10 days of AS and was preceded by an increase in the rate of ribosome formation. MHC mRNA levels remained unchanged during AS. These findings demonstrate that cardiac protein synthesis is accelerated in response to pressure overload by an initial increase in translational efficiency, followed by an adaptive increase in translational capacity during sustained hypertrophic growth.

Animals↗
PubMed1999

[Moyamoya disease with intraventricular hemorrhage due to rupture of lateral posterior choroidal artery aneurysm: case report].

Intracranial aneurysms associated with moyamoya disease are often reviewed. Aneurysms not around the circle of Willis but on the collateral vessels are rare. A 71-year-old woman presented with sudden onset of severe headache and vomiting. CT scan showed an intraventricular hemorrhage from bilateral lateral ventricle to fourth ventricle. Cerebral angiography showed the occlusion of the terminal portion of the bilateral internal carotid artery with moyamoya vessels and three aneurysms at the distal portion of the left lateral posterior choroidal artery. Clinical symptoms improved day by day, but 17 days later, due to rebleeding of the aneurysms the patient fell into coma. The day after rebleeding, endovascular embolization was performed using liquid particle, and the left lateral posterior choroidal artery and the aneurysm were occluded. Brain infarction with massive brain edema of the left cerebral hemisphere resulted in the patient's death. The management of the aneurysms in the basal ganglia and on the collateral vessels associated with moyamoya disease is controversial. We suggest positive intervention during the acute stage for the peripheral artery aneurysms taking endovascular embolization into consideration to prevent rupture or rebleeding.

Aged↗
PubMed1999

Hematological effects of a low-prime neonatal cardiopulmonary bypass circuit utilizing vacuum-assisted venous return in the porcine model.

Limiting hemodilution in neonates is difficult when extracorporeal circuits require priming volumes that are 2 to 3 times the blood volume of the newborn patient. This extreme hemodilution contributes to the development of significant postbypass coagulation disturbances. The purpose of this project was to design a low-prime neonatal bypass circuit and evaluate the coagulation status after reduced hemodilution. The null hypothesis stated there is no significant difference in the measured coagulation parameters between the low-prime circuit and the standard high-prime circuit. Four neonatal piglets (2-4 kg) were divided into two groups and placed on cardiopulmonary bypass using either a low- (200 ml) or high-prime (500 ml) circuit. Both groups were cooled to 20 degrees C, and, following cardioplegic arrest, underwent circulatory arrest for 20 minutes. The low-prime circuit used vacuum-assisted venous drainage, which permitted the circuit to be at the patient level. The high-prime circuit required fresh washed donor red blood cells to maintain the hematocrit in the desired range of 15-20%. The platelet count on bypass decreased by 60 +/- 1.0% in the low-prime group versus 79.6 +/- 0.1% in the high-prime group. Following bypass, the platelet count was reduced by 38.3 +/- 14.3% in the low-prime versus 60.2 +/- 2.6% in the high-prime group. During rewarming, the mean heparinase activated clotting time (ACT) increased 5.1% above baseline in the low-prime group and 53.5% above baseline in the high-prime group. Mean plasma-free hemoglobin levels increased 40.4 mg/dl in the low-prime group versus 62.1 mg/dl in the high-prime group during bypass. This laboratory evaluation of a low-prime neonatal circuit demonstrates that coagulation disturbances often present in neonates can be reduced with the use of a low-prime circuit.

Animals↗
PubMed1999

[Studies on simultaneous determination of 17 organochlorine and 9 pyrethroid pesticides of agricultural products].

A method for simultaneous determination of 17 organochlorine and 9 pyrethroid pesticides in agricultural products by capillary GC with ECD detection was studies. The samples were extracted with acetone under acidic conditions followed by Florisil column clean-up and then injected into a GC-ECD. The organochlorine pesticides used in this study included unstable captan and captafol in the homogenized preparations of fruits and vegetables. Captan and captafol were also found to decompose in rice and wheat samples when the samples were allowed to stand after the addition of water. Addition of phosphoric acid to the samples was effective in preventing the decomposition of captan and captafol. Recovery of the pesticides investigated in this study was not decreased by the addition of phosphoric acid. Addition of phosphoric acid was also effective in removing interfering substances from onion extract. Recovery of organochlorine and pyrethroid pesticides from samples spiked at levels of 0.05-0.25 ppm by the proposed method was 51.4-100.8% for rice and wheat and 60.1-119.0% for vegetables.

Chromatography, Gas↗
PubMed1998

Induction of apoptosis by SB202190 through inhibition of p38beta mitogen-activated protein kinase.

p38, a subfamily of the mitogen-activated protein kinase, regulates gene expression in response to various extracellular stimuli. The pyridinyl imidazoles like SB202190 are specific inhibitors of p38alpha and p38beta and have been widely used in investigation of the biological functions of p38. Here we show that SB202190 by itself was sufficient to induce cell death, with typical apoptotic features such as nucleus condensation and intranucleosomal DNA fragmentation. SB202190 stimulated the activity of CPP32-like caspases, and its apoptotic effect was completely blocked by the protease inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone and expression of bcl-2. In addition, SB202190 was able to potentiate apoptosis induced by Fas(APO-1) ligation or UV irradiation. Expression of p38beta attenuated the apoptotic effect of SB202190 and the cell death induced by Fas ligation and UV irradiation. In contrast, expression of p38alpha induced cell death mildly. These results indicate that SB202190 induces apoptosis through activation of CPP32-like caspases and suggest that distinct members of the p38 subfamily of mitogen-activated protein kinase have different functions in apoptosis.

Apoptosis↗
PubMed1998

DNA replication cycle in parthenogenetically developing eggs of the starfish Asterina pectinifera.

Starfish oocytes artificially activated by a calcium ionophore will develop normally if the formation of polar bodies is suppressed. In the present paper, schedules of the DNA replication period (S phase) of these parthenogenotes were explicitly timed using 5-bromo-2'-deoxyuridine (BrdU) and anti-BrdU monoclonal antibody. Their schedule of S phase was identical to that of fertilized eggs. Consequently, an S phase regulation system is triggered even in parthenogenotes raised by dual treatment of egg activation and polar body suppression. The S phase schedule of parthenogenotes confirms the temporal pattern of chromosome duplication, observed by other researchers, leading to tetraploid parthenogenotes. The S phase determination also provides a basis for argument concerning the number of centrioles participating in parthenogenetic development. If polar body formation of activated eggs was not suppressed, the first S phase was normal, but the second S phase did not recur on time. A rigidly regulated system of DNA replication cycle, which should be an essential prerequisite for parthenogenesis, thus requires the content of polar bodies.

Animals↗
PubMed1998

Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase.

IkappaB kinases (IKKalpha and IKKbeta) are key components of the IKK complex that mediates activation of the transcription factor NF-kappaB in response to extracellular stimuli such as inflammatory cytokines, viral and bacterial infection, and UV irradiation. Although NF-kappaB-inducing kinase (NIK) interacts with and activates the IKKs, the upstream kinases for the IKKs still remain obscure. We identified mitogen-activated protein kinase kinase kinase 1 (MEKK1) as an immediate upstream kinase of the IKK complex. MEKK1 is activated by tumor necrosis factor alpha (TNF-alpha) and interleukin-1 and can potentiate the stimulatory effect of TNF-alpha on IKK and NF-kappaB activation. The dominant negative mutant of MEKK1, on the other hand, partially blocks activation of IKK by TNF-alpha. MEKK1 interacts with and stimulates the activities of both IKKalpha and IKKbeta in transfected HeLa and COS-1 cells and directly phosphorylates the IKKs in vitro. Furthermore, MEKK1 appears to act in parallel to NIK, leading to synergistic activation of the IKK complex. The formation of the MEKK1-IKK complex versus the NIK-IKK complex may provide a molecular basis for regulation of the IKK complex by various extracellular signals.

Animals↗