Search PubMed⌕ Search

Biomedical subjects

M Uchida

Publications and source records attributed to M Uchida.

At least 163 records · Page 9Linked to original sources

The inhibitory effect of vitamin E on arachidonic acid metabolism during the process of urethane-induced lung tumorigenesis in mice.

It is known that change in the arachidonic acid metabolism plays an important role in the development of tumors. This study was undertaken to understand the relationship of changes in lipoxygenase, cyclooxygenase and ornithine decarboxylase (ODC) to the inhibitory effect of vitamin E on urethane-induced lung tumorigenesis in mice. We analyzed the inhibitory effect of vitamin E on ornithine decarboxylase, cyclooxygenase and lipoxygenase activities at a promotion phase of lung tumorigenesis in mice. An increase in the ODC of urethane treated-mice and no significant change in the ODC of VE-treated mice were observed. An increase in the production of PGE2 and all HETES tested in the lungs of the urethane-treated mice was observed at week 8 after injection (promotion phase), showing a significant difference compared to the control group. Excessive vitamin E feeding during the initiation or promotion phases inhibited the increase in PGE2 and HETES produced by urethane treatment. These results suggest that the suppression of prostagrandin metabolism and ODC may be associated with the inhibitory effect of vitamin E against urethane-induced lung tumorigenesis.

Animals↗

[Social support of chronically-ill children and healthy children].

The purpose of this study was to describe characteristics of social support of chronically-ill children and to compare social support of chronically-ill children with those of healthy children. Subjects consisted of 204 chronically-ill children aged between 9 and 18 years old and 544 healthy children aged between 10 and 17 years old. Results of this study were as follows: 1. In both chronically-ill children and healthy children, parents' support score and teachers' support score were significantly higher in elementary school children than high school students. In both groups, friends' support score was significantly higher in girls than boys. 2. Chronically-ill children reported significantly higher scores of parents' support, friends' support and teachers' support than those of healthy children. 3. Parents' support score was significantly lower in children with diabetes than those with asthma and cancer. 4. The total score of social support and teachers' support score were significantly lower in children with employed mothers than those with unemployed mothers. 5. The total social support score of children who participated in non-sports extracurricular activities was significantly higher than those of children who did not participate in non-sports activities.

Adolescent↗

Resection of the caudate lobe of the liver for primary and recurrent hepatocellular carcinomas.

BACKGROUND: Resection of the caudate lobe of the liver to treat malignancies has recently received attention, but long-term results after such resection for hepatocellular carcinoma have not been reported for an acceptable number of patients. This study analyzed the short- and long-term results after resection of the caudate lobe for primary and recurrent hepatocellular carcinoma in 19 patients. STUDY DESIGN: Complete or partial resection of the caudate lobe was performed for the treatment of primary (n = 13) and recurrent (n = 6) hepatocellular carcinoma. Eleven patients had a solitary tumor only in the caudate lobe, but eight patients had tumors in other segments of the liver as well. There were 16 men and 3 women. Age ranged from 35 to 79 years, averaging 63 years. Clinicopathologic features of these cases were evaluated from various viewpoints. RESULTS: The duration of the operation ranged from 80 to 250 minutes (mean plus or minus standard deviation; 149 +/- 47) and blood loss from 200 to 2,400 g (836 +/- 651). Four patients (21.8 percent) had postoperative complications and one (5.3 percent) died of postoperative variceal bleeding. Tumor size ranged from 1.0 to 6.0 cm, averaging 3.7 +/- 1.4. A capsule was seen around the tumor in 68.4 percent, daughter nodules in 5.3 percent, and vascular invasion in 31.2 percent. Hepatic cirrhosis was present in 15 patients and chronic hepatitis in four. The 5-year survival rate in all patients was 31.3 percent. The survival rate was significantly better in patients with primary hepatocellular carcinoma than in those with recurrent tumors (49.2 percent compared with none) because of frequent recurrence in the latter group. CONCLUSIONS: Resection of the caudate lobe of the liver for hepatocellular carcinoma associated with chronic hepatic disease can be performed safely with a satisfactory long-term result, particularly in patients with primary tumors in this lobe.

Aged↗

Arterial vascular abnormality accompanying cerebral cortical dysplasia.

We report a case of dysplastic arterial vascular abnormality in a 32-year-old man with overlying neuronal cell migration disorder. MR images showed a thickened left insular cortex adjacent to the abnormal vascular network. These findings suggest the possibility of leptomeningeal damage during neuronal cell migration as the cause of the overlying vasculopathy. The true pathogenesis of these seemingly associated abnormalities is unknown.

Adult↗

[Vesical malacoplakia accompanied with bilateral hydronephrosis: a case report].

A 63-year-old female with a complaint of pollakisuria was referred to our clinic for the treatment of bilateral hydronephrosis. Ultrasonography, computerized tomography (CT) scan and magnetic resonance imaging (MRI) revealed bilateral hydronephrosis due to stenosis of the vesicoureteral junction, which was caused by a nodular mass on the posterior wall of the bladder. Cystoscopy revealed a yellowish-white mass on the trigone. Bilateral percutaneous nephrostomy for the treatment of chronic renal failure due to bilateral hydronephrosis and transurethral resection of bladder tumor were performed. Histological findings indicated a chronic granuloma with Michaelis-Gutmann body and the tumor was diagnosed as vesical malacoplakia. Oral administration of trimethoprim sulfamethoxazole, bethanecol chloride and vitamin C was done for the conservative therapy of malacoplakia. However, stenosis of the vesicoureteral junction remained. Then, bilateral vesicoureteroneostomy was performed and there was no obvious recurrence of malacoplakia 20 months postoperatively.

Female↗

[Involvement of enhanced glutamate release in halogenated volatile anesthetic-induced excitation in mouse brain].

The present experiments aimed to elucidate the mechanisms of excitatory effects of volatile anesthetics. In ddN mice, enflurane (2% in air), sevoflurane (2%) or isoflurane (1.2%) induced opisthotonus. In ddY mice, a halogenated ethane, tetrachlorodifluoroethane (CCl2FCCl2F:DF-112, 2%) induced tonic-clonic convulsion. These CNS excitatory effects were suppressed by pretreatment with an N-methyl-D-aspartate antagonist, MK-801 (0.5mg.kg-1). Halogenated volatile anesthetics (enflurane, sevoflurane, isoflurane and halothane) increased glutamate release from synaptosomes of the mouse cerebral cortex at concentrations corresponding to those used clinically. The convulsive gas, DF-112, released glutamate more potently than the anesthetics. These data suggest the involvement of enhanced glutamate release in the mechanisms of excitatory effects of halogenated volatile anesthetics.

Anesthetics, Inhalation↗

Adjuvant chemotherapy with epirubicin and carmofur after radical resection of hepatocellular carcinoma: a prospective randomized study.

The intrahepatic recurrence rate is extremely high, even after radical resection of hepatocellular carcinoma (HCC). One report showed intra-arterial administration of epirubicin to be effective in the treatment of nonresectable HCC. We evaluated the effect of postoperative adjuvant chemotherapy including this drug. Fifty-seven patients who had undergone radical resection of HCC were entered in this study. Using the sealed-envelope method, 27 patients were assigned to a group undergoing resection only and 29 patients to a group also receiving adjuvant chemotherapy after resection. The protocol of the chemotherapy was intra-arterial administration of epirubicin (40 mg/m2) at 1 month after resection followed by intravenous administration of epirubicin (40 mg/m2) every 3 months for 2 years. In addition, 1-hexylcarbamoyl-5-fluorouracil (HCFU; carmofur), 300 mg/d, was administered orally every day, beginning from 1 month after the resection and continuing (in principle) for 24 months. The clinicopathologic backgrounds were well randomized between the two groups. The chemotherapy protocol was performed completely in only five patients (7.2%). Twenty-four (82.8%) patients had to cease the protocol due to various reasons: change to a new therapy after recurrence of HCC in 19 cases (79.2%), severe side effects of the chemotherapy in three cases (12.5%), liver failure in one case (4.2%), and a postoperative complication in one case (4.2%). The mean total doses were 128 +/- 114 mg for epirubicin and 144 +/- 84 g for HCFU. The cumulative overall and disease-free survival rates for 5 years were not significantly different between the two groups. The results of this prospective randomized study suggest that this adjuvant chemotherapy protocol with epirubicin and HCFU after radical resection of HCC was not effective.

Antibiotics, Antineoplastic↗

Biotransformation of the novel inotropic agent toborinone (OPC-18790) in rats and dogs. Evidence for the formation of novel glutathione and two cysteine conjugates.

The metabolism of toborinone, (+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quin - olinone, a novel inotropic agent, was studied in rats and dogs after intravenous administration. Chemical structures of the 13 metabolites were characterized by direct-probe FAB/MS and field desorption/MS, LC/FAB/MS, and various NMR measurements. After intravenous dosing of 10 mg/kg [14C]toborinone, fecal and urinary recoveries of the 14C dose were approximately 70% and 26-30%, respectively, in both rats and dogs. The predominant component of radioactivity was the unchanged toborinone in every biological specimen in rats and dogs. Although unchanged toborinone was predominantly observed, toborinone underwent extensive conjugations with glucuronic acid, sulfate, and glutathione, either directly or following phase I reaction. Metabolites resulting from oxidative N-C cleavage were minor both in number and in quantity in every biological specimen in rats and dogs. In rats, toborinone underwent O-demethylation to form M-7 and successive phase it reaction to yield the glucuronide M-1 and the sulfoconjugate M-2, and deconjugation to yield M-7, which was a primary metabolite accounted for 35.67% of the radioactivity excreted in the feces by 48 hr. Conjugates M-1 and M-2 were the major metabolites in rat plasma. In dogs, toborinone was metabolized via mercapturic acid pathway to yield the primary metabolites, cysteine conjugates M-10 and M-11 that accounted for 19.10% and 6.70% of the radioactivity excreted in the feces by 48 hr and that were detected species specifically in dogs. The glutathione conjugate M-13, which was isolated from in vitro incubations using dog liver, led us to consider a possible mercapturic acid pathway from the parent compound to M-10. Metabolites in dog plasma and those in urine in both rats and dogs were minor in quantity. The metabolic pathways of toborinone in rats and dogs are proposed herein.

Animals↗

[Automatic movements of extremities induced in primary massive brain lesion with apneic coma].

In three cases of primary massive brain lesion with apneic coma, various automatic movements of the extremities were elicited by physical or sensory stimulation. In each case, these movements appeared after a period of cessation of spontaneous respiration followed by flaccid tetraplegia. Brainstem reflexes were absent throughout in all cases. The movements were induced mainly by ventroflexion of the neck, and each case showed movements as described below: in the first case, the patient flexed her elbows and raised both arms slowly, a typical Lazarus sign; in the second case, the patient raised both arms and showed myoclonic movements; and the third case showed abduction of both legs and extension in the upper extremities. Pathology in the first case showed ischemic changes in the entire brain and brainstem. Although ischemic change was also found in the anterior horn cells and white matter of the spinal cord of C1-C4 and of T4 and below, the spinal cord of C5-T3 was relatively well-preserved. These movements appear to have essentially originated in spinal neurons; however, it is assumed that they must have recovered from spinal shock which occurred due to upper level transection. These movements were induced by ventroflexion of the neck, so mechanical extension of the spinal roots, mechanical compression of the spinal cord, and various modalities of the sensation afferent might have some relation to these movements. As tonic neck reflex might also be a cause of these, movements, association with the lower medulla could not be ruled out completely. These movements appeared nearing or after brain death. Although in each case of brain death the spinal cord may have been affected by specific conditions, such as impaired circulation of whole central nervous sysytem, it might have been transversed at upper level, which then causes spinal automatism. These movements might appear even in the state of brainstem death. In each case, the distribution and severity of hypoxic changes in the spinal cord may have resulted in variations in the type and characteristics of these movements.

Aged↗

Thyroxine-binding globulin and thyroid hormones after resection of hepatocellular carcinoma.

OBJECTIVES: Some human hepatocellular carcinomas (HCCs) produce thyroxine-binding globulin (TBG). High serum TBG levels in such patients may be associated with increased thyroxine (T4) levels. This study aimed to elucidate the serum TBG and thyroid hormone profile in Japanese patients with HCC, to compare the difference between TBG-producing and -nonproducing HCCs, and to investigate the changes in serum TBG level and the thyroid hormone profile after removal of the tumor. METHODS: The 40 subjects included 20 patients with HCC, 10 healthy controls, and 10 operative controls. Serum TBG, 3,5,3'-triiodothyronine (T3), T4, and free T4 were measured serially for 4 wk after resection of HCC in 16 patients and after control operations in 10 patients. Assay methods were a radioimmunoassay for TBG and enzyme immunoassays for T3, T4, and free T4. RESULTS: Values higher than the mean +/- 2 SD of controls were considered abnormally high. Of patients with HCC, 60% had abnormally high TBG values, 65% had abnormally high T3 values, 39% had abnormally high T4 values, and 6% had abnormally high free T4 values. The mean levels of TBG and T3 were significantly higher than those in healthy controls, but no difference was found for T4 and free T4 levels. There were no significant differences in various clinicopathological factors between patients with high TBG levels and those with normal TBG levels. After resection of HCC, serum TBG decreased significantly in patients with high TBG levels but not in those with normal TBG levels. CONCLUSIONS: This study shows that >50% of HCCs in Japanese patients produce TBG; removal of the tumor reduces serum TBG in such cases.

Adult↗

Functional assessment of two vitamin D-responsive elements in the rat 25-hydroxyvitamin D3 24-hydroxylase gene.

Two vitamin D-responsive elements (VDRE-1 and VDRE-2) were recently identified in the 5'-upstream region of the rat 25-hydroxyvitamin D3 24-hydroxylase gene at -151/-137 and -259/-245, respectively. We studied the transcriptional regulation of this gene by vitamin D by means of mutational analysis. Introducing mutations into VDRE-1 and VDRE-2 in the native promoter -291/+9 reduced vitamin D-dependent chloramphenicol acetyltransferase activity by 86 and 41%, respectively. Mutation of the direct repeat -169/-155 located at 3 base pairs upstream of VDRE-1 also caused 50% decrease of chloramphenicol acetyltransferase activity. Connection of the element -169/-155 to VDRE-1 enhanced the vitamin D responsiveness of VDRE-1 5-fold through the heterologous beta-globin promoter. The fragment -291/-102 containing the two VDREs showed two shifted bands in the presence of the vitamin D receptor and retinoid X receptor in gel retardation analysis, and the appearance of the slower migrating band indicates that two sets of receptor complexes bind to this fragment simultaneously. These results demonstrate that VDRE-1 is a stronger mediator of vitamin D function than VDRE-2 due to the presence of the accessory element -169/-155 located adjacent to VDRE-1, although VDRE-2 exhibits a smaller dissociation constant for the vitamin D receptor-retinoid X receptor complex than VDRE-1.

Animals↗

The activation of K-ras gene at an early stage of lung tumorigenesis in mice.

To clarify the exact timing of K-ras gene mutational activation in lung tumorigenesis of mice, we applied a sensitive mutant allele specific amplification (MASA) method to pulmonary DNA from urethane-treated mice. The activation of K-ras gene with 61st codon AT mutation was detected in the lungs of mice at day 14 but not day 7 after urethane treatment by MASA. The mutation of MASA products was also checked by XbaI restriction fragment length polymorphism analysis and DNA sequencing. These data suggest that the mutation of K-ras gene in the lungs of mice treated with urethane occurred at the early stage of lung tumorigenesis.

Animals↗

Repeat hepatectomy for recurrent hepatocellular carcinoma.

This study evaluated the results of repeat hepatectomy for recurrent hepatocellular carcinoma (HCC) and delineated the limitations of such a treatment strategy. Of 290 patients who had radical hepatic resection, 167 had intrahepatic tumour recurrence. Fifty patients underwent a second hepatectomy. Third and fourth hepatectomies were carried out on six and two patients respectively. There were 36 men and 14 women. Age ranged from 32 to 77 years (mean 59.1 years). Liver cirrhosis was present in 38 and chronic hepatitis in 12 patients. Operative death occurred in four patients (8 per cent) after a second and in one of six after a third hepatectomy, compared with 4.5 per cent after first hepatectomy. The five postoperative deaths were attributed to either Child grade B or C liver disease, or severe intraoperative bleeding. The 5-year survival rate was better in these 50 patients (41 per cent) than in 117 patients who were treated otherwise (7 per cent). The present study indicates that repeat hepatectomy may be useful for recurrent HCC. It is indicated principally for patients with a solitary tumour and Child grade A liver disease.

Adult↗

FK506 maintains cellular calcium homeostasis in ischemia-reperfusion injury of the canine liver.

Increased morbidity and mortality following transplantation surgery due to the primary nonfunction and dysfunction of the liver poses a great challenge and has increased the crescendo of research work in this field. In this study, we have tried to address the issue concerning the changes in Ca2+ homeostasis and hepatic microcirculation in 90 min of ischemia followed by reperfusion of the liver after FK506 pretreatment. Twenty dogs divided into two groups; group I (0.15 mg/kg/day FK506 for 3 days, im) and group II (control) were used for the measurement of mitochondrial (mit) and total cellular Ca2+ by atomic absorption spectrophotometer and hepatic microcirculation with laser Doppler flowmeter. Serum AST leakage was significantly (P < 0.05) suppressed in group I at 6 hr after reperfusion. The percentage gain in mit Ca2+ in group I was significantly (P < 0.05) inhibited compared to that in group II at 15 min after reperfusion and also when compared with the preischemic value it was significantly (P < 0.05) elevated at 30 min after reperfusion in group II only. FK pretreatment significantly (P < 0.05) inhibited the overload in total cellular Ca2+ at 15 and 30 min after reperfusion. Moreover, hepatic microcirculation was significantly (P < 0.001) better in group I between 2 and 6 hr after reperfusion. In conclusion, the ameliorating property of FK in ischemia-reperfusion may be explained by prevention of the cellular Ca2+ overload during the perireperfusion period.

Animals↗

Changes in the cerebral arteriovenous oxygen content difference by surgical incision are similar during sevoflurane and isoflurane anaesthesia.

PURPOSE: To investigate changes of cerebral arteriovenous oxygen content difference (AVDO2) induced by surgical incision and to determine carbon dioxide (CO2) reactivity of the cerebral circulation during sevoflurane and isoflurane anaesthesia. METHODS: Twenty-one ASA 1-2 patients undergoing elective surgery for supratentorial tumours were randomly allocated to receive either 1.3 MAC sevoflurane/N2O anaesthesia (n = 10) or equi-MAC isoflurane/N2O anaesthesia (n = 11). Before and after incision, haemodynamic measurements and AVDO2 determinations were performed. After opening the dura, AVDO2 was determined before and after the respiration rate was increased by 50%. RESULTS: Incision produced an increase in mean arterial pressure from 69 +/- 11 to 97 +/- 22 mmHg (mean +/- SD) (P < 0.0005) and from 71 +/- 6 to 89 +/- 12 mmHg (P < 0.0001) in the sevoflurane and isoflurane groups, respectively, whereas the heart rate increased from 60 +/- 9 to 72 +/- 8 bpm (P < 0.001) and from 65 +/- 6 to 70 +/- 7 bpm (P < 0.001), respectively. Arterial carbon dioxide tension (PaCO2) was increased from 33.6 +/- 2.3 to 34.6 +/- 1.8 mmHg (P < 0.05) with incision in the sevoflurane group. The AVDO2 was decreased from 6.5 +/- 1.6 to 5.3 +/- 1.6 vol% (P < 0.0005) in the sevoflurane group and from 6.7 +/- 1.1 to 6.0 +/- 1.1 vol% (P < 0.01) in the isoflurane group. The % change of AVDO2 was larger in the sevoflurane group than in the isoflurane group (-18.3 +/- 8.4% vs -9.1 +/- 9.0%; P < 0.05) but no difference remained after the post-incisional AVDO2 value of the sevoflurane group was corrected for pre-incisional PaCO2. Carbon dioxide reactivity, calculated as the percent change in AVDO2 per mmHg change in PaCO2, was 6.1 +/- 3.0%.mmHg-1 in the sevoflurane group and 5.9 +/- 2.4%.mmHg-1 in the isoflurane group (P = NS). CONCLUSIONS: Sevoflurane and isoflurane are associated with similar impairment of cerebral flow-metabolism coupling at incision, while CO2 reactivity is maintained during both anaesthetics.

Adult↗

Erdheim-Chester disease: a case report with immunohistochemical and biochemical examination.

This report describes a 47-year-old man with Erdheim-Chester disease (EC), the second case reported in Japan. The patient complained of knee pain, and the roentgenogram of the bilateral legs revealed symmetric osteolytic lesions with sclerosis of the metaphyseal regions of the long bones. Histological examination of the biopsy specimen showed a xanthogranulomatous lesion consisting of aggregations of foamy macrophages and Touton-type giant cells. Immunohistochemical study of the foamy cells in the lesion showed positive reaction to anti-Kp-1, anti-S-100 alpha, beta, anti-neuron-specific enolase (NSE), anti-alpha-1-antichymotrypsin, anti-alpha-1-antitrypsin, and anti-lysozyme antibodies. Electron microscopy showed many lipid droplets in the cytoplasm, but no Langerhans granules. These results suggested that the disease was part of the spectrum of histiocytosis but was different from Langerhans cell histiocytosis. Biochemical analysis of material extracted from a lesion showed the predominance of cholesterol ester. The disease progressed to central diabetes insipidus, and the involvement of multiple organs was indicated by a magnetic resonance image.

Bone Diseases↗

Effect of pituitary adenylate cyclase-activating polypeptide on exocrine and endocrine secretion in the ovine pancreas.

The role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of exocrine and endocrine pancreas was investigated in conscious sheep. Intravenous infusions of PACAP-27 and PACAP-38 (1, 3, and 10 pmol/kg/min) for 10 min during phase II of the duodenal migrating myoelectric complex accelerated pancreatic protein and amylase outputs dose-dependently. The responses in enzyme secretion to both PACAPs at the highest doses were inhibited significantly by atropine infusion (14.4 nmol/kg/min). Vasoactive intestinal polypeptide (VIP) at 3 pmol/kg/min significantly accelerated protein but not amylase outputs, although the response to the highest dose was not significantly influenced by atropine. PACAP-27 and VIP increased pancreatic juice flow and bicarbonate output dose-dependently; however, the responses to the highest dose were not altered significantly by atropine. On the other hand, intravenous injection of PACAP-38 (100 pmol/kg) did not influence basal plasma concentration of insulin, glucagon, and glucose. Moreover, PACAP-38 (1-100 pmol/kg) altered neither pancreatic endocrine response to intravenous infusion of glucose (20 mumol/kg/min) not that to n-butyric acid (33 mumol/kg/min). These results suggest that PACAP contributes to the regulation of exocrine secretion of the ovine pancreas but not to endocrine secretion. PACAP appears to accelerate pancreatic enzyme secretion mostly via the cholinergic nerves.

Animals↗

Dose-response curve for anaesthetics based on the Monod-Wyman-Changeux model.

We have analysed the dose-response curve for halothane and isoflurane according to the Monod-Wyman-Changeux (MWC) model. This model describes the nature of the physiological data reported by Wakamori, Ikemoto and Akaike for inhibitory Cl currents induced by GABA or glycine in dissociated rat brain neurones and by Herrington and colleagues for Ca2+ currents in clonal pituitary cells. With some assumptions on the difference in response to anaesthetics between patients, the model is applicable in vivo, and it also describes well the human dose-response curve for isoflurane reported by Mather, Raftery and Prys-Roberts. However, the steeply sigmoidal dose-response curve in humans for halothane presented by deJong and Eger is difficult to understand with the same model, because it gives rise to unrealistic MWC variables.

Anesthetics, Inhalation↗