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Biomedical subjects

S Nemoto

Publications and source records attributed to S Nemoto.

At least 55 records · Page 3Linked to original sources

Opposing effects of Jun kinase and p38 mitogen-activated protein kinases on cardiomyocyte hypertrophy.

c-Jun N-terminal protein kinase (JNK) and p38, two distinct members of the mitogen-activated protein (MAP) kinase family, regulate gene expression in response to various extracellular stimuli, yet their physiological functions are not completely understood. In this report we show that JNK and p38 exerted opposing effects on the development of myocyte hypertrophy, which is an adaptive physiological process characterized by expression of embryonic genes and unique morphological changes. In rat neonatal ventricular myocytes, both JNK and p38 were stimulated by hypertrophic agonists like endothelin-1, phenylephrine, and leukemia inhibitory factor. Expression of MAP kinase kinase 6b (EE), a constitutive activator of p38, stimulated the expression of atrial natriuretic factor (ANF), which is a genetic marker of in vivo cardiac hypertrophy. Activation of p38 was required for ANF expression induced by the hypertrophic agonists. Furthermore, a specific p38 inhibitor, SB202190, significantly changed hypertrophic morphology induced by the agonists. Surprisingly, activation of JNK led to inhibition of ANF expression induced by MEK kinase 1 (MEKK1) and the hypertrophic agonists. MEKK1-induced ANF expression was also negatively regulated by expression of c-Jun. Our results demonstrate that p38 mediates, but JNK suppresses, the development of myocyte hypertrophy.

Animals↗

Cepharanthine inhibits proliferation of cancer cells by inducing apoptosis.

Cepharanthine, a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata was examined for a possible apoptosis-inducing effect in murine P388 doxorubicin-sensitive (P388/S) and -resistant (P388/DOX) cells. A significant increase in LDH release from cells was observed after P388/S and P388/DOX cells had been exposed to cepharanthine for 24 h. Cepharanthine (10 micrograms/ml) markedly induced apoptosis in resistant cells after 6 h and 24 h. By the means of agarose electrophoresis the DNA ladder was detected in cell lines treated with cepharanthine for 24 h. Cepharanthine (1-10 micrograms/ml) also induced the production of reactive oxygen species in P388/DOX cells, while no such cepharanthine-induced increase in reactive oxygen species was observed in P388/S cells. Flow cytometry analysis showed a high level of Fas-antigen expression in P388/DOX cells treated with cepharanthine. Furthermore, we found that the inhibitition of DNA and protein synthesis caused by cepharanthine (10 micrograms/ml) was more significant in resistant cells than in sensitive cells. Cepharanthine had no effect on the GSH content of P388/S and P388/DOX cells. Our experimental results suggest that cepharanthin can induce apoptosis both in P388/S and P388/DOX cells, especially in the latter. Apoptosis induced by cepharanthine may be implicated in the production of reactive oxygen species and Fas-antigen expression in tumor cells.

Alkaloids↗

Arteriovenous malformations in the basal ganglia and thalamus: management and results in 101 cases.

OBJECT: Because arteriovenous malformations (AVMs) in the basal ganglia and thalamus are difficult to treat, the authors conducted a retrospective study to determine the best management strategy for these lesions. METHODS: The authors reviewed the management and outcome in 101 patients with AVMs treated between 1971 and 1995. In 15 conservatively treated patients, hemorrhage occurred in 71.4% (annual rate 11.4%), and the morbidity and mortality rates were 7.1% and 42.9%, respectively, during a mean follow-up period of 6.6 years. Total microsurgical resection was performed in 15 patients with no mortality resulting, but motor function deteriorated permanently in three of them (20%). Postoperative morbidity correlated well with the location of the AVM and with preoperative motor function. In cases of lenticular AVMs without motor weakness, a postoperative decrease in motor function was significantly more common than in the remaining patients. In patients with motor weakness before surgery, AVMs in the thalamus or caudate nucleus were successfully resected. Among 66 patients treated with gamma knife radiosurgery, three had permanent radiation-induced neurological deficits, and three others experienced bleeding (new bleeding in one case and rebleeding in two). The treatment-associated morbidity rate was 6.7%, and the actuarial rate of complete obliteration was 85.7% at 2.5 years. In five patients treated with embolization alone, the morbidity and mortality rates associated with the procedure or bleeding were 40% and 20%, respectively. The morbidity and mortality rates in the pre-gamma knife era were 22.2% and 22.2%, whereas those for the post-gamma knife era are currently 10.4% and 1.5%, respectively. CONCLUSIONS: These results indicate that conservatively treated AVMs are more likely to bleed and thus produce a high incidence of patient mortality. Multimodal treatment including radiosurgery, microsurgery, and embolization improved clinical outcomes by making it possible to treat difficult cases successfully.

Adolescent↗

Cavernous sinus sampling in patients with adrenocorticotrophic hormone-dependent Cushing's syndrome with emphasis on inter- and intracavernous adrenocorticotrophic hormone gradients.

OBJECT: As an alternative method to inferior petrosal sinus sampling with administration of corticotropin-releasing hormone (CRH), the authors have developed a method of selective venous sampling directly from the cavernous sinus, which is performed using a superselective catheterization technique. The goal of this study is to assess this method. METHODS: Catheterization to the cavernous sinus was performed in 44 patients with clinical and biochemical features of Cushing's syndrome. Forty of these patients in whom there was a definite clinical and/or histological diagnosis were evaluated. In 35 patients, a pituitary microadenoma was detected on magnetic resonance imaging and/or during surgery. Ectopic lesions were suspected in five patients, who later developed nonpituitary tumors. The central/peripheral (C/P) ratios of adrenocorticotrophic hormone (ACTH) without CRH administration ranged from 5.2 to 448.1 (mean+/-standard deviation, 66.7+/-91.2) in cavernous sinuses and from 1.1 to 52 (mean+/-standard deviation, 8.5+/-9.9) in the inferior petrosal sinuses. The petrosal sinus sampling contained false negative results in eight patients (23%) based on a cutoff point of 2. On the contrary, patients with ectopic lesions did not show any increase in ACTH levels in either sampling portion. The intercavernous gradients of ACTH, ranging from 1.2 to 506.4, indicated the correct lateralization of microadenoma in the lateral wing in all 30 patients. The interpetrosal gradients, ranging from 1 to 31.4, did not give a sufficient value (> or = 1.4) in four patients (13%) with a lateral lesion. In five cases of midline tumors, the intercavernous and interpetrosal gradients indicated false laterality in three and four cases, respectively. The intracavernous (posterior-anterior) gradients, ranging from 1.04 to 60.7 (mean 14.9), showed a higher concentration of ACTH in the posterior portion of the sinus in all patients. CONCLUSIONS: These results suggest that 1) cavernous sinus sampling without CRH administration can demonstrate hypersecretion of ACTH from the pituitary gland with a high diagnostic accuracy; 2) intercavernous gradients will indicate the correct lateralization in laterally localized microadenomas; and 3) sampling should be performed from the posterior portion of the cavernous sinus.

Adolescent↗

[Combination of transcatheter arterial infusion of SMANCS and embolization (SMANCS-TAE) for hepatocellular carcinoma--second report].

Patients with unresectable hepatocellular carcinoma (hepatoma) with hypervascularity were treated by SMANCS-TAE. A superselective catheterization technique was used to inject gelatin sponge particles after administration of SMANCS. In 30 patients of first hepatoma treated by SMANCS-TAE. Grade 4 was obtained after 1.7(1-3) courses. The 2-year survival rate was 22%. Some of the 24 patients of second hepatoma treated by SMANCS-TAE have survived over 2 years. Sixteen patients with advanced hepatoma (Vp2-3 or T4) were treated only by SMANCS injection, but none survived over 1 year. SMANCS-TAE appears to have the same potential and safety as L-TAE, when used selectively. Moreover, we can reduce the course of treatment and obtain good QOL for hepatoma patients except in advanced cases.

Aged↗

Identification of c-Jun NH2-terminal protein kinase (JNK)-activating kinase 2 as an activator of JNK but not p38.

c-Jun NH2-terminal protein kinase (JNK), a distant member of the mitogen-activated protein (MAP) kinase family, regulates gene expression in response to various extracellular stimuli. JNK is activated by JNK-activating kinase 1 (JNKK1), a dual specificity protein kinase that phosphorylates JNK on threonine 183 and tyrosine 185 residues. Here we show that JNKK2, a novel member of the MAP kinase kinase family, was phosphorylated and activated by MEKK1, a MAP kinase kinase kinase in the JNK signaling cascade. JNKK2 activity was also stimulated by constitutively active forms of Rac and Cdc42Hs, members of the Rho small GTP-binding protein family. Unlike JNKK1 that activates both JNK and p38 MAP kinases, JNKK2 stimulated only JNK. Transient transfection assays demonstrated that JNKK2 potentiated the stimulation of c-Jun transcriptional activity by MEKK1. The existence of multiple JNK-activating kinases may contribute to the specificity of the JNK signaling cascade.

Amino Acid Sequence↗

Sclerosing inflammatory pseudotumor arising from the carotid artery region.

We report a 42-year-old female patient with sclerosing inflammatory pseudotumor. She had found a mass in her left neck after she caught a cold. An elastic hard mass (25 x 15 mm), unaccompanied by any other symptoms, was palpated adjacent to the left carotid bifurcation. The mass extended vertically along the common carotid artery, partially adhering to the pulsating artery. Under ultrasonography, the mass was characterized by a homogenized low echoic shadow surrounding the left common carotid artery. Angiography revealed a slight narrowing of the common carotid artery with a surrounding hypovascular mass. Computerized tomography (CT) and magnetic resonance imaging (MRI) both showed a mass enclosing the carotid artery; a Ga scintigram also showed a highly concentrated mass. Surgical removal of the mass included removing part of the carotid artery, internal and external carotid arteries and sympathetic trunk. The left internal jugular vein was transplanted to connect the common carotid artery to the internal carotid artery. Although the hypoglossal and vagus nerves adhered to the mass, they were preserved by sharp dissection with the scalpel. Although hypoglossal and vagus nerve dysfunction were observed temporarily after the surgery, Horner's syndrome appeared and persisted. Histological examination revealed markedly fibrotic tissues surrounding the carotid artery with extensive lymphocyte and plasmacyte infiltration and a diagnosis of sclerosing inflammatory pseudotumor was made.

Adult↗

Activation at the germinal vesicle stage of starfish oocytes produces parthenogenetic development through the failure of polar body extrusion.

Starfish oocytes can be fertilized after germinal vesicle breakdown (GVBD) and artificial parthenogenesis can be induced by activating the oocytes after GVBD (post-GVBD activation). In the present study, parthenogenotes were obtained by the activation of immature oocytes with caffeine before treatment with 1-methyladenine (1-MeAde) to induce oocyte maturation. Most of the caffeine-treated eggs developed as tetraploids, as parthenogenotes produced by the post-GVBD activation. The parthengenotes were derived only from eggs that failed to extrude polar bodies, mostly from eggs failing to extrude a second polar body. Eggs derived from immature oocytes activated by A23187, treated with 1-MeAde and post-treated with cytochalasin B failed to extrude polar bodies, and eventually developed into parthenogenetic embryos. These results indicate that the present parthenogenesis mechanism shares the same characteristics as that achieved by post-GVBD activation in the suppression of polar body formation as a key means for successful starfish parthenogenesis.

Adenine↗

Effect of high concentration of ascorbate on catalase activity in cultured cells and tissues of guinea pigs.

This study showed that the inhibition of cell growth in 3T6, induced by the supplementation of ascorbate at 0.5 mM in cultured medium, was prevented by the addition of catalase in the range of 25-750 units/mL regardless of the degree of activity. However, cytotoxicity induced by concentrations of more than 2 mM ascorbate could not be prevented even when a high level of catalase (5,000 units/mL) was added to the medium. Catalase activity in medium supplemented with ascorbate decreased with incubation time; the higher the concentration of ascorbate, the greater the decrease in catalase activity. These results indicate that even though catalase is present at a high concentration in the medium, it cannot prevent cytotoxicity by a high concentration of ascorbate because the oxygen radical derived from ascorbate inhibits its activity. We therefore investigated whether the inhibition of catalase activity by ascorbate could be observed in animal tissues. The catalase activity in the tissues of guinea pigs 6h after the administration of ascorbate was lower than that in non-administered animals. When guinea pigs were fed diets containing 5 mg or 100 mg ascorbate/animal over a 90 weeks period, a clear affect on catalase activity in the high-dose ascorbate group as compared to that in the low-dose ascorbate group was not observed.

Animals↗

[Dural arteriovenous fistula involving the superior sagittal and transverse-sigmoid sinuses, treated by thrombolysis: case report].

A rare case of dural arteriovenous fistula (DAVF) in the superior sagittal sinus (SSS), the transverse sinus and the sigmoid sinus is reported. A 64-year-old man, who had had an episode of temporary visual disturbance after moderate fever for a week about 20 years before, was aware of loss of visual acuity and reduced field of view in the right eye. When he was introduced to our outpatient service, increased intracranial pressure (ICP) was detected by lumbar puncture. Cerebral angiograms showed bilateral DAVFs both in the posterior fossa and the SSS concomitant with thrombosis in the transverse sinus, sigmoid sinus and SSS. Afterwards, endovascular transarterial embolization through bilateral occipital, posterior auricular and left middle meningeal, superior temporal arteries was carried out. In addition, transvenous thrombolytic therapy using a catheter inserted into SSS resulted in the improvement of his visual problems. Although he was discharged at once, he was readmitted to our department with Foster Kennedy syndrome and increased ICP. Cerebral angiograms showed recurrence of both DAVF and sinus thrombosis. Transarterial embolization was performed again resulting in a significant reduction of DAVF, and his visual acuity was recovered to a moderate degree. The origin of DAVF is still controversial. Although two theories, "congenital" and "acquired", are put forward, it has been thought that both factors play important roles. In our case, the patient had stenosis in the jugular canal portions of the sigmoid sinus. In addition, sinus thrombosis seemed to have occurred. It is thought that increased intrasinus pressure may have lead to communication with surrounding arteries through existing dural vessels. We applied transvenous thrombolytic therapy in this case. Our result suggests that we should consider this therapy for some cases of DAVF.

Arteriovenous Fistula↗

[Effects of milrinone in patients undergoing cardiac surgery].

We investigated effects of milrinone in twenty consecutive patients (6 adults, 1 child, and 3 early infants) during cardiac surgery requiring cardiopulmonary bypass (CPB). The operations were: CABG 5, CABG+mitral valve repair 2, MVR 2, redo-MVR 4, aortic surgery 3 (total arch replacement 2), VSD+pulmonary hypertension 2 (infants), Tetralogy of Fallot 1, and PDA aneurysm 1 (infant). Ten minutes after release of aortic cross-clamp, all patients received milrinone by loading dose (50 micrograms/kg, bolus), followed by a continuous infusion of 0.5 or 0.75 microgram/kg/min. All of patients weaned from CPB with milrinone and low-dose of dopamine. The 75% of patients did not require any other drugs except for milrinone during post operative ICU stay. At the same time, we evaluated the effect of milrinone on platelet number in the patients before and after CPB. Milrinone administration did not cause significant changes in platelet number after CPB. No adverse effects attributable to this drug were found. Milrinone appears to be effective and safe in patients undergoing cardiac surgery of all kinds.

Adult↗

[Stenosis of Carpentier-Edwards pericardial bioprosthesis in the tricuspid position caused by adhesion of native valve cusps to the bioprosthesis].

We experienced a case of dysfunction of Carpentier-Edwards pericardial bioprosthesis in the tricuspid position. Explanted bioprosthesis showed overgrowth of neointima from ring to cusps and adhesion to remnants of native cusps. This restricted the motion of the pericardial leaflets resulting in orifice stenosis. Care must be taken in such valve replacement by this prosthesis leaving native valve tissue.

Aged↗

[Studies on the stability of 89 pesticides in organic solvent].

The stability of 89 pesticides (17 organochlorine, 33 organophosphorus, 8 pyrethroid, 12 carbamate, and 19 other pesticides) in 6 kinds of organic solvents (methanol, ethanol, 2-propanol, ethyl acetate, n-hexane, and acetone) was investigated using gas chromatography/mass spectrometry (GC/MS). All of the investigated pesticides were stable in all of the tested organic solvents during storage for 6 hours at room temperature in the dark except captafol, captan, phosmet, chinomethionat, and dicofol. However, the decreases of captafol, captan, phosmet, and chinomethionat were observed in methanol. The decreases of captafol, captan, and phosmet were also observed in ethanol. Moreover, the decrease of dicofol was observed in acetone. The decrease of captafol dissolved in methanol at a concentration of 2 micrograms/ml was faster than those of captan, phosmet, and chinomethionat; the residual captafol was 75% after 30 min of storage. Dicofol dissolved in acetone also decreased during storage in a refrigerator. 4,4'-dichlorobenzophenone (DCBP) and chlorobutanol were detected in the acetone solution of dicofol after storage. Furthermore, it was found that dicofol was decomposed by acetone at an injection port, and DCBP and chlorobutanol were formed when it was injected into GC with acetone.

Carbamates↗

[Specific determination of deltamethrin and tralomethrin by preparative HPLC and GC-ECD].

Tralomethrin quickly changes to deltamethrin in gas chromatograph by debromination. Therefore deltamethrin and tralomethrin are not able to be distinguished by gas chromatographic determination. A method for specific determination of deltamethrin and tralomethrin was established. The method consists of fractionation by high performance liquid chromatography and determination by gas chromatography. Recoveries of deltamethrin and tralomethrin spiked to three agricultural products were from 42 to 78% and from 18 to 76%, respectively with relative standard deviations ranging from 0.3 to 15%. From the analysis of samples spiked with tralomethrin, it was found that a part of tralomethrin quickly changed to deltamethrin in homogenate of agricultural products. The addition of phosphoric acid to the homogenate did not prevent the change of tralomethrin.

Chromatography, Gas↗

Myocardial adaptive changes and damage in ischemic heart disease.

Changes in two of the elements of myocardial subcellular organelles relating to cardiac energetics, ventricular myosin isozymes and mitochondrial DNA mutations, were examined using left ventricular tissue samples obtained at autopsy from patients with ischemic heart disease. Myosin isozymes were examined in tissues from nine patients with ischemic heart disease and 12 control patients with cancer but no heart disease. Extracted myosin was separated by pyrophosphate gel electrophoresis. The relative concentration of each component was determined by densitometry. Mitochondrial DNA mutations were evaluated in tissues from ten patients with myocardial infarction and 11 control patients with cancer but no heart disease. DNA was extracted and mitochondrial DNA mutations were detected by the polymerase chain reaction. Two bands were revealed by pyrophosphate gel electrophoresis. These contained VM-A, which exhibited faster electrophoretic mobility and was present in lower concentrations, and VM-B, which had a lower mobility and a higher concentration, respectively. SDS polyacrylamide gel electrophoresis showed that these two components contained the heavy chain and light chains 1 and 2 of myosin. VM-A concentrations tended to be higher in patients with ischemic heart disease than in controls. A 7.4-kb deletion was detected between the D-loop and the ATPase 6 genes of mitochondrial DNA from the myocardium of 6 out of 10 patients with myocardial infarction. The relative amounts of the two myosin isozymes could be altered by ischemic heart disease, although the functional significance of these components is unclear. The changes in the two myosin isozymes might be an adaptive change to disordered energy metabolism, but this change was small. The myocardial mitochondrial DNA deletions in patients with myocardial infarction were thought to result from ischemic damage.

DNA, Mitochondrial↗

Interactions of the F1-ATPase subunits from Escherichia coli detected by the yeast two-hybrid system.

Subunit interactions among the F1-ATPase subunits were studied by the yeast two-hybrid system. Various pairwise combinations of genes encoding alpha, beta, gamma, delta and epsilon subunits of Escherichia coli H+-ATPase fused to the DNA-binding or activation domain of the yeast GAL4 gene were introduced into yeast and expression of a reporter gene encoding beta-galactosidase was detected. Combinations of the alpha and beta subunit genes, and of the epsilon and gamma subunit genes showed high levels of reporter gene expression, while those of alpha and delta, beta and delta, gamma and delta, and delta and epsilon demonstrated weak but significant reporter gene expression. However, combinations of alpha and gamma, beta and gamma, alpha and epsilon, and beta and epsilon did not induce reporter expression. None of the fused genes alone induced reporter gene expression. These results suggested that specific and strong interactions between the alpha and beta, gamma and epsilon, and weak interactions between the alpha and delta, beta and delta, and gamma and delta subunits occurred in yeast cells in the two-hybrid system. Effects of previously identified mutant beta subunits with Leu-40 to Pro. Glu-41 to Lys or Pro-332 to Gln substitutions which caused defects in molecular assembly of F1-ATPase were analyzed with regard to alpha-beta interactions. No interaction of the alpha and beta subunits was observed in this system using the beta subunit with mutation of Pro-332 to Gln. However, for the other two mutations, alpha-beta interactions were observed. This system may be useful for isolating mutants which have defects in interaction of F1-ATPase subunits.

Escherichia coli↗

Combined treatment of a dural arteriovenous malformation of the lateral sinus using transarterial and direct lateral sinus embolisation.

An 80-year-old man presented with a dural arteriovenous malformation (DAVM) involving the left lateral sinus. A carotid angiogram showed the lateral sinus to be occluded proximally and distally, with unusual retrograde venous outflow from the residual sinus to the cortical veins, including a dilated vein of Labbé. Single photon emission computed tomography showed reduced left frontal and temporal cerebral blood flow. We concluded that the risk of bleeding from the DAVM was high and that the patient needed to be treated immediately. However, his age made surgical removal of the DAVM hazardous and we therefore chose to treat him by transarterial and direct lateral sinus embolisation via a burr hole.

Aged↗