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Biomedical subjects

M Nemoto

Publications and source records attributed to M Nemoto.

At least 37 records · Page 2Linked to original sources

[Difference in 201TlCl accumulation mechanism in brain tumors: a comparison of their Na(+)-K+ ATPase activities].

The accumulation levels of 201TlCl and Na(+)-K+ ATPase activity in tumor tissue were compared among glioblastoma, benign glioma and meningioma to study the difference in the mechanism of 201TlCl accumulation. The subjects were 19 cases comprised of 6 glioblastoma, 2 oligodendroglioma, 1 fibrillary astrocytoma, 1 pilocytic astrocytoma and 9 meningioma. Preoperative 201TlCl SPECT was performed in all the cases, and Thallium Index (TL index) was calculated by a ratio of 201TlCl in the tumor area and the contralateral area. In addition, cell membrane was extracted from the tumor tissue collected intraoperatively to determine Na(+)-K+ ATPase activity. No statistically significant difference in TL index was noted between the glioblastoma group (6.97 +/- 2.67) and the meningioma group (5.87 +/- 1.99). This fact showed that there was no difference in the accumulation level of 201TlCl between the two groups. On the other hand, the glioblastoma group indicated a higher value of Na(+)-K+ ATPase activity (49.13 +/- 43.76 mumole/hour/mg protein) than the meningioma group (7.73 +/- 13.84 mumole/hour/mg protein) (p < 0.05, t test). These results suggested the involvement of Na(+)-K+ ATPase activity in 201TlCl accumulation in glioblastoma and the influences of other accumulation mechanism than Na(+)-K+ ATPase activity such as the volume of intratumoral vascular bed in meningioma.

Adult↗

Pharmacological aspects of ipecac syrup (TJN-119)-induced emesis in ferrets.

In order to elucidate the precise mechanism of ipecac syrup (TJN-119) on the occurrence of vomiting, we examined the effects of ipecac syrup on the abdominal afferent nerve activity as well as on the 5-HT levels of the ileum and area postrema in ferrets. Oral administration of TJN-119 (0.5 mg/kg) produced a significant increase in afferent abdominal vagus nerve activity which lasted approximately 1 hour. The maximum response induced by TJN-119 was estimated to be 219 +/- 18% of the pre-injection level. Cephaeline or emetine, the main alkaloids of ipecac syrup, also demonstrated similar effects on afferent vagus nerve activity. TJN-119 increased the 5-HT content in the ileum but not in the area postrema. These observations illustrate possible mechanisms that may act at peripheral sites. It was recently reported that TJN-119 has a high affinity to 5-HT4 receptors (Hasegawa et al., unpublished data). These results suggest that 5-HT4 receptors may be involved in the emetic action of TJN-119.

Afferent Pathways↗

Differentiation-induced insulin secretion from nonendocrine cells with engineered human proinsulin cDNA.

To investigate the effects of differentiation on insulin secretion from engineered nonendocrine cells, modified human proinsulin cDNA (INS/fur) was transfected to THP-1 monocyte and C2C12 myoblast cell lines. When THP-1 was differentiated into macrophages with phorbol ester, the insulin secretion rate was increased by 3.1-fold. This increase in insulin secretion is accompanied by a 17.6-fold increase in the processing efficiency of the modified human proinsulin and by a 3.5-fold increase in the abundance of furin mRNA. In addition, differentiation of C2C12 into myotubes, which can be induced by changing the serum, showed a 9.9-fold increase in insulin secretion and was accompanied by a 1.6-fold increase in the abundance of furin mRNA. The involvement of posttranslational processing and the exocytotic process in differentiation-induced insulin secretion could lead to the possibility of regulation of insulin secretion from genetically engineered cells.

3T3 Cells↗

A comparative study of the anatomy of rat and human livers.

To compare the fundamental structure of the human liver, in relation to that of the rat a comparative study was performed, in which 20 rat livers and 78 human cadaver livers were examined. The rat livers had four lobes (left, middle, right, and caudate). The left and middle lobes formed a single lobe but the middle lobe had a deep notch to which the round ligament attached. The right lobe was split into two sub-lobes and the caudate lobe was divided into the paracaval portion and the Spiegel lobe, which was split into two sub-lobes. The left, right, and caudate lobes had one primary portal branch, whereas the middle lobe had two portal branches. The left and the right sub- and caudate lobes had one large hepatic vein each, whereas three large hepatic veins were observed in the middle lobe. Based on the ramifying patterns of the portal and hepatic veins, the rat middle lobe possessed left and right hepatic components and a main portal fissure. The following rat hepatic lobes were equivalent to the following human liver segments: the left lobe to segment II; the middle lobe to segments III, IV, V, and VIII; and the right lobe to segments VI and VII. The fundamental structures of rat and human livers were similar, and the findings demonstrated a new interpretation of the anatomy of the human liver.

Animals↗

Preferential transmission of maternal allele with DQA1*0301-DQB1*0302 haplotype to affected offspring in families with type 1 diabetes.

To approach the possible involvement of an epigenetic mechanism in the pathogenesis of type 1 diabetes, we investigate here a parent-of-origin effect in transmission of the susceptible alleles at HLA-DQ loci by the transmission disequilibrium test. When we examined alleles of affected offspring of Japanese origin in 28 nuclear families, the maternal alleles were significantly different from the paternal alleles. Furthermore, the maternal alleles with the susceptible DQA1*0301-DQB1*0302 haplotype showed strong transmission disequilibrium with antiglutamic acid decarboxylase antibody-positive type 1 diabetes, while the paternal alleles with the same haplotype did not. This differential transmission disequilibrium of the susceptible allele was confirmed by the contingency table analysis for transmitted or nontransmitted alleles of both parental origin. The unique transmission of the susceptible allele observed supports the hypothesis that an epigenetic mechanism including genomic imprinting at the HLA-DQ region is involved in the pathogenesis and the genetic complexity of type 1 diabetes.

Asian People↗

Evaluation of serum uric acid changes in different forms of hepatic vascular inflow occlusion in human liver surgeries.

Uric acid values in serum have been analyzed as one of the markers to predict cellular damage due to ischemia reperfusion injury in the field of organ transplantation. The present study was conducted to confirm that uric acid values in serum could be an efficient marker of ischemic injury of liver parenchyma following hepatic vascular occlusion in human liver surgery. The changes in serum uric acid values were analyzed at fixed intervals during different liver surgeries. Significant increases in serum uric acid values were observed in patients who received the Pringle's maneuver in which hepatic vascular inflow was manipulated with a repetition of 15 min occlusion and 5 min perfusion, whereas almost no changes in uric acid values were found in both groups of patients who received the hemilobal occlusion of the Glisson's triad in which the right or left vessels were manipulated with a repetition of 30 min occlusion and 5 min perfusion and the "control method" in which the hepatic vessels of the lesion side were previously cut before liver resection. Uric acid values in serum increased in patients of Pringle's maneuver compared to those of the hemilobal occlusion of the Glisson's triad and the control method though these procedures were used in larger hepatectomies rather than Pringle's maneuver. The results indicated that serum uric acid values do not always reflect the severity of ischemia of the liver parenchyma but reflect intestinal congestion because marked intestinal congestion was observed in patients of Pringle's maneuver but not in patients of the hemilobal occlusion of the Glisson's triad and the control method. The evaluation of the severity of the ischemic injury of the liver should be done with caution when uric acid is used as a marker in human liver surgery.

Adolescent↗

Major organ function under mechanical support: comparative studies of pulsatile and nonpulsatile circulation.

We examined a major organ function during 3 h biventricular assisted circulation after acute myocardial infarction model in the pig. In left ventricular circulation, the outflow cannula was placed in the ascending aorta and an inflow cannula through the mitral valve in the left ventricle. A pump (pulsatile group, Zeon Medical, Inc., Tokyo, Japan and nonpulsatile group, Nikkiso HPM-15, Nikkiso, Inc., Tokyo, Japan) was connected to each cannula. In right ventricular circulation, the outflow cannula was placed in the pulmonary artery and an inflow cannula in the right ventricle. The right ventricular circulation was supported by a nonpulsatile pump (Nikkiso HPM-15). The items measured were the regional blood flows of the cortex and medulla in the kidney, white matter and gray mater in brain, and liver; renal arterial flow; carotid arterial flow; portal vein flow; common hepatic arterial flow; arterial ketone body ratio (AKBR); and lactate/pyrubic acid (L/P). In the pulsatile group, the renal cortical blood flow increased, and the medulla blood flow decreased. On the other hand, in the nonpulsatile group, both regional blood flows decreased. That means that in the pulsatile assisted group intrarenal redistribution improved rather than in the nonpulsatile assisted group. In addition the liver regional blood flow, AKBR, and L/P showed significant differences between the pulsatile and nonpulsatile groups. On the other hand, the white matter and gray matter regional blood flows and carotid arterial flow did not show significant differences between the groups. The results of our study indicated that pulsatile circulation produced superior circulation in the kidney and liver, and microcirculation on the cell level was superior as well in early treatment of acute heart failure.

Animals↗

Analysis of optical signals evoked by peripheral nerve stimulation in rat somatosensory cortex: dynamic changes in hemoglobin concentration and oxygenation.

The origins of reflected light changes associated with neuronal activity (optical signals) were investigated in rat somatosensory cortex with optical imaging, microspectrophotometry, and laser-Doppler flowmetry, and dynamic changes in local hemoglobin concentration and oxygenation were focused on. Functional activation was carried out by 2-second, 5-Hz electrical stimulation of the hind limb under chloralose anesthesia. These measurements were performed at the contralateral parietal cortex through a thinned skull. Regional cortical blood flow (rCBF) started to rise 1.5 seconds after the stimulus onset, peaked at 3.5 seconds (26.7% +/- 9.7% increase over baseline), and returned to near baseline by 10 seconds. Optical signal responses at 577, 586, and 805 nm showed a monophasic increase in absorbance coincident with the increase in rCBF; however, the signal responses at 605 and 760 nm were biphasic (an early increase and late decrease in absorbance) and microanatomically heterogeneous. The spectral changes of absorbance indicated that the concentrations of both total hemoglobin and oxyhemoglobin increased together with rCBF; deoxyhemoglobin, increased slightly but distinctly (P = 0.016 at 1.0 seconds, P = 0.00038 at 1.5 seconds) just before rCBF increases, then decreased. The authors conclude that activity-related optical signals are greatly associated with a moment-to-moment adjustment of rCBF and metabolism to neuronal activity.

Animals↗

[Unilateral visual field defect due to optic nerve compression by sclerotic internal carotid artery: a case report].

A case of unilateral visual field defect due to optic nerve compression by a sclerotic internal carotid artery was reported. A 71-year-old woman was admitted to our department because of constricted visual field of the right eye. MRI showed elevation of the right optic nerve compressed by an internal carotid artery. The right carotid angiography revealed elevation and distortion of the C1-2 portion. Frontal craniotomy was carried out and the optic nerve was visualized on this side. The right optic nerve was found to have been compressed by the sclerotic internal carotid artery. The optic canal was then unroofed. The post-operative course was uneventful. The visual field was improved. When last seen 6 months after surgery, her visual field remained in the improved condition. Nasal field abnormalities are most frequently encountered in retinal and anterior optic nerve pathology. Our success in improving the visual field disturbance may be accounted for by the fact that the preoperative period was short and the operation was performed before atrophy of ocular fundi occurred. Nasal field loss caused by intracranial lesions of the optic pathway is rare. It is probably impossible to determine degree of the symptomatology caused by direct-pressure compression as opposed to that caused by ischemia secondary to occlusion of small arterial supply branches. Vascular compressive neuropathy of optic nerve should not be diagnosed simply by the radiological finding of the optic nerve dislocation. However, optic nerve compression by surrounding arteries should be remembered as one of the possible causes of visual field defect which needs to be treated surgically.

Aged↗

[Extraneural metastasis of pineal germinoma through a ventriculoperitoneal shunt, following histological change].

Primary germinoma of the central nervous system carries a good prognosis because of their radiosensitivity. Recurrence is rare and extraneural metastases are even more unusual. We report a unique case of a primary intracranial germinoma exhibiting complete response to radiotherapy, but recurring as an intra-abdominal yolk sac tumor. The presence of a VP shunt is thought to have facilitated metastatic spread of the intracranial neoplasm. An 21-year-old (corrected) male was admitted with headache and consciousness disturbance. Computed tomography (CT) revealed an enhanced tumor of the pineal region and hydrocephalus. A ventriculo-peritoneal shunt was emplaced immediately. No serum tumor markers such as alpha-fetoprotein or human chorionic gonadotropin were detectable. A test dose of radiotherapy (whole brain 20Gy) was given. The tumor size was remarkably decreased. Clinical diagnosis was germinoma. Additional whole brain radiation (total 45Gy) and whole spine radiation (20Gy) were given. The tumor and the hydrocephalus regressed completely and the patient returned to school. Three years later, he experienced a feeling of abdominal fullness. CT and echotomography of the abdomen showed a large peritoneal and intra-hepatic tumor. But MRI revealed no recurrent tumor of the pineal lesion or of the other areas in the central nervous system. Radiological and clinical findings showed no tumors in the testis, the retroperitoneal cavity, or the thymus. Laboratory investigation demonstrated elevated serum AFP (26,550 ng/ml). AFP level regressed after combined chemotherapy. However, the patient died due to pneumonia and multiple organ failure. Only needle necropsy was performed. The microscopic appearance of the peritoneal tumor was confirmed to be an endodermal sinus tumor. It was suspected to be a metastasis of the pineal tumor through the V-P shunt system.

Adult↗

[A case of mitral valve replacement combined with idiopathic thrombocytopenic purpura (ITP)].

We conducted mitral valve replacement (MVR) in a patient with mitral regurgitation (MR) complicated with idiopathic thrombocytopenic purpura (ITP). The patient was a 62-year-old male who was diagnosed to have grade IV MR. However, a decrease in platelet count was noted (5.6 x 10(4)/microliter) when he has admitted to this hospital for operation. After detailed examination, he was diagnosed to have ITP. Though mass intravenous infusion of gamma-globulin (400 mg/kg/day, for 5 days) was done before the operation, the treatment was not successful and splenectomy was consequently conducted. In view of the influence of invasive splenectomy, the change in platelet count was carefully observed thereafter. The count subsequently increased to reach a peak (26.9 x 10(4)/microliter) after 2 weeks from the splenectomy. MVR was conducted when the count started to decrease again after the peak. The operation was safely completed without any complication such as hemorrhage during and after the operation. Since gamma-globulin treatment and splenectomy are sometimes ineffective in ITP, it is advisable to wait an operation until the effects of these treatments are clarified.

Heart Valve Prosthesis Implantation↗

Differential effects of talipexole and bromocriptine on serotonin release from rat intestinal tissues--an in vitro study of the emetic response of antiparkinsonian dopamine agonists.

In order to elucidate the role of emetic action, the effects of talipexole and bromocriptine, two antiparkinsonian dopamine receptor agonists, on serotonin (5-HT) release from enterochromaffin (EC) cells were studied by measuring 5-HT concentrations in the perfusate of the isolated rat ileum. Bromocriptine (10(-8)-10(-6) M), which exerts agonistic effects on D1 and D2 receptors, increased 5-HT release in a concentration-dependent manner. No significant increase in 5-HT release was seen after addition of talipexole, which selectively stimulates D2 receptors and blocks 5-HT3 receptors, even at 10(-6) M. The increase in 5-HT release caused by bromocriptine at 10(-6) M was inhibited by administration of 10(-6) M of D1 receptor antagonist SCH 23390, D2 receptor antagonist spiperone, 5-HT3 receptor antagonist granisetron or tetrodotoxin (TTX). These results showed the involvement of both dopaminergic and serotonergic mechanisms in the 5-HT release from EC cells following the administration of dopamine receptor agonists. Bromocriptine might induce 5-HT release by stimulating D1, D2 and 5-HT3 receptors and depolarizing neurons in the ileum. On the other hand, talipexole might weaken 5-HT release from EC cells elicited by D2 receptor stimulation with its 5-HT3 receptor blocking property. It is suggested that the emetic effect of dopamine receptor agonists involves the peripheral gastrointestinal tract as their site of action.

Administration, Oral↗

Effects of various 5-HT3 receptor antagonists, granisetron, ondansetron, ramosetron and azasetron on serotonin (5-HT) release from the ferret isolated ileum.

The object of this study was to evaluate the involvement of 5-HT3 receptors in the regulation of 5-HT release from the small intestine using ferrets, an animal model of emesis. 2-Methyl-5-HT, a 5-HT3 receptor agonist, produced a concentration-dependent increase of 5-HT from the ferret ileum. This increase in 5-HT release was significantly inhibited by granisetron (10(-7) and 10(-6) M) or azasetron (10(-7) and 10(-6) M) in a concentration-dependent manner. Ondansetron (10(-7) M) and ramosetron (10(-6) M) also significantly inhibited the 2-methyl-5-HT-induced increase in 5-HT release. When the concentration of ondansetron was increased from 10(-7) M to 10(-6) M, inhibition of 5-HT release was reduced. Ramosetron, for which 5-HT3 receptor binding of the rat brain is remarkably stronger than for any other 5-HT3 receptor antagonists, inhibited the 5-HT release at only the highest concentration of 10(-6) M. Based on these observations that the mode of action on the 2-methyl-5-HT induced 5-HT release is different among 5-HT3 receptor antagonists, it is suggested that there is a possibility that the neuronal 5-HT3 receptors and the 5-HT3 receptors on the EC cells may represent two distinct subtypes.

Animals↗

Viscosity of diluent and sensory level of subarachnoid anaesthesia achieved with tetracaine.

PURPOSE: Our objective was to evaluate the effect of viscosity in determining the cephalad spread of tetracaine administered by the subarachnoid route. METHODS: We studied 42 patients that were randomly assigned to receive subarachnoid anaesthesia for arthroscope of the knee. They received 8 mg tetracaine dissolved in either glucose 10%, sodium chloride (NaCl) 5%, glucose 5%, or NaCl 2.5%. The specific gravity and viscosity of each solvent was also measured. Cephalad spread was defined as the level of sensory block achieved. RESULTS: The specific gravity of the glucose 5% and the NaCl 2.5% solutions were similar (1.0197 +/- 0.0001 vs 1.0177 +/- 0.0001 (mean +/- SD)). That was also true for the more concentrated pair of solutions (1.0385 +/- 0.0001 for glucose 10% vs 1.0353 +/- 0.0003 in NaCl 5%). However, the viscosities of the 10% and 5% solutions of glucose (0.01178 +/- 0.0002 and 0.01020 +/- 0.0002 (g.cm-1.sec-1)) were higher (P < 0.05) than that of the other two solutions, being 0.00955 +/- 0.0001 for NaCl 5% and 0.00934 +/- 0.0002 for NaCl 2.5%. The median maximal extent of sensory block achieved was significantly higher (P < 0.05) with a solution of tetracaine in glucose 10% injected into the subarachnoid space at the L3-4 interspace than that observed in the two groups administered tetracaine in NaCl. The level of sensory block 30 min after the injection of anaesthetic was; T3 [T1-6] (median [range]) with glucose 10%, T6 [T4-10] with NaCl 5%, T5 [T2-11] with glucose 5%, and T5.5 [T2-11] with NaCl 2.5%. CONCLUSION: Viscosity was shown to be one of determinants of the clinical extent of spread of a subarachnoid anaesthetic such as tetracaine.

Adolescent↗

[Microcirculation of kidney and skin during left ventricular assisted circulation--comparative studies of pulsatile and nonpulsatile assists].

We examined microcirculation of the kidney and skin over a six-hour period in an acute myocardial infarction model in pigs. The outflow cannula was placed in the ascending aorta, the inflow cannula was placed the in left atrium, and a pump was connected to each (pulsatile group, Zeon Medical pneumatic pump; nonpulsatile group, Nikkiso HPM-15). Items examined included the regional blood flow of the cortex and medulla in the kidney and skin, renal and carotid arterial flow, arterial ketone body ratio (AKBR), lactate/pyruvic acid (L/P), BUN, creatinine, and beta 2-microglobulin. After the experimental study, the major organs were removed and a pathological study was performed. The mean aortic pressure after the assist could be maintained at about 100 mmHg. There were no significant differences between the two groups in mean aortic pressure and total cardiac output. Under assisted circulation, the pulse pressure was maintained at about 15 mmHg in the nonpulsatile group and about 40 mmHg in the pulsatile group. After the assist, there were no significant differences in the carotid arterial blood flow between the two groups. However, there were significant differences between the two groups in the renal arterial, renal cortical, and regional skin blood flows. In the laboratory data, there were significant differences between the two groups in AKBR, L/P, and beta 2-microglobulin. Pathological findings on the kidney in the nonpulsatile group showed expansion of the proximal tubes, retention of red blood cells, and expansion of blood capillaries within the glomerulus. On the other hand, the pulsatile group showed almost normal formation. In the lungs, the nonpulsatile group showed edematous change in the air cells and the pulsatile group showed almost normal formation. The results of the previous and current study indicated that the pulsatile assist produced superior circulation in the kidney and peripheral organs and superior cellular metabolism in the early treatment of acute left cardiac failure. On the other hand, nonpulsatile assisted circulation was found to be ineffective in maintaining the circulation in the body, and to be potentially capable of causing irreversible damage of major organs if continuous for more than three hours. The results also indicated that pulsatility was necessary to maintain normal circulation in the peripheral organs and cellular metabolism in the early treatment of acute left cardiac failure.

Animals↗

A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity.

The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that has a pivotal role in adipocyte differentiation and expression of adipocyte-specific genes. The PPARgamma1 and gamma2 isoforms result from alternative splicing and have ligand-dependent and -independent activation domains. PPARgamma2 has an additional 28 amino acids at its amino terminus that renders its ligand-independent activation domain 5-10-fold more effective than that of PPARgamma1. Insulin stimulates the ligand-independent activation of PPARgamma1 and gamma2 (ref. 5), however, obesity and nutritional factors only influence the expression of PPARgamma2 in human adipocytes. Here, we report that a relatively common Pro12Ala substitution in PPARgamma2 is associated with lower body mass index (BMI; P=0.027; 0.015) and improved insulin sensitivity among middle-aged and elderly Finns. A significant odds ratio (4.35, P=0.028) for the association of the Pro/Pro genotype with type 2 diabetes was observed among Japanese Americans. The PPARgamma2 Ala allele showed decreased binding affinity to the cognate promoter element and reduced ability to transactivate responsive promoters. These findings suggest that the PPARgamma2 Pro12Ala variant may contribute to the observed variability in BMI and insulin sensitivity in the general population.

Adult↗

High predictive value of red cell volume measurement using carboxy-haemoglobin in a rabbit model of haemorrhage.

We have studied the accuracy of blood volume measurements using carbon monoxide (CO)-labelled haemoglobin (COHb) injection and dilution (CO method) by comparing changes in red cell volume (RCV) measured using the CO method and 51Cr-labelled erythrocyte dilution (51Cr method) in a haemorrhage and infusion model in rabbits. RCV was measured repeatedly using the CO method at four different blood volume stages (stages I-IV). At stages I and IV, RCV was measured simultaneously using the 51Cr method. In comparing the sum of the circulating RCV and extracted RCV (SUM RCV) using the CO method, the values were almost equal and there were no significant differences between the values at the four stages. In comparing circulating RCV measured using the CO method and the 51Cr method, mean difference between the two methods was 0.80 (SD 0.76) ml kg-1 or 4.7 (4.6)%, and a positive correlation was observed (r = 0.91). We conclude that the CO method can be used to measure blood volume during perioperative periods in infants because it avoids use of a radioactive tracer, is simple and repeated measurements are possible.

Animals↗