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Biomedical subjects

M Uchida

Publications and source records attributed to M Uchida.

At least 217 records · Page 12Linked to original sources

[A case of renal cell carcinoma in a young adult].

Renal cell carcinoma in young adults under the age of forty is rare. A case of renal cell carcinoma in a 22-year-old female is presented. Microhematuria was pointed out in the patient by a health check up system and an ultrasonogram revealed a solid mass 5 cm in diameter in the lower pole of the right kidney. The patient was referred to our clinic in January, 1994. An abdominal CT showed a solid and well bordered mass in the right kidney. Renal tumor biopsy was revealed renal cell carcinoma. Right radical nephrectomy was performed on February 9, 1994. From 1986 to 1994, 4 cases of renal cell carcinoma in young adults, other than this case, have been treated in our clinic. All of them have been healthy for more than 6 years, suggesting a good prognosis.

Adult↗

Exon redefinition by a point mutation within exon 5 of the glucose-6-phosphatase gene is the major cause of glycogen storage disease type 1a in Japan.

Glycogen storage disease (GSD) type 1a (von Gierke disease) is an autosomal recessive disorder caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase). We have identified a novel mutation in the G6Pase gene of a individual with GSD type 1a. The cDNA from the patient's liver revealed a 91-nt deletion in exon 5. The genomic DNA from the patient's white blood cells revealed no deletion or mutation at the splicing junction of intron 4 and exon 5. The 3' splicing occurred 91 bp from the 5' site of exon 5 (at position 732 in the coding region), causing a substitution of a single nucleotide (G to T) at position 727 in the coding region. Further confirmation of the missplicing was obtained by transient expression of allelic minigene constructs into animal cells. Another eight unrelated families of nine Japanese patients were all found to have this mutation. This mutation is a new type of splicing mutation in the G6Pase gene, and 91% of patients and carriers suffering from GSD1a in Japan are detectable with this splicing mutation.

Adult↗

Symbrachydactyly involving both the hand and foot. A report of two cases.

Symbrachydactyly involving both the hand and foot is extremely rare. Two such cases are described. The first patient was a two-month-old female with symbrachydactyly of the left hand and foot. The second patient was a one-year-old female with symbrachydactyly of the right hand and foot. No other abnormalities were identified. The diagnosis of this congenital anomaly is discussed and the literature reviewed.

Female↗

Congenital heart defects in Aarskog syndrome.

We report on 10 Japanese individuals from 3 families affected with Aarskog syndrome. Pulmonary stenosis and ventricular septal defect with spontaneous closure were detected respectively, in 2 of them as an uncommon finding. A review documented 169 non-Japanese cases (2 with congenital heart defects), while of 30 Japanese individuals reported till now, 4 (including ours) had cardiac anomalies. We propose that this combination is not coincidental and that in all cases of Aarskog syndrome a cardiac evaluation is indicated.

Abnormalities, Multiple↗

Identification of a vitamin D-responsive element in the 5'-flanking region of the rat 25-hydroxyvitamin D3 24-hydroxylase gene.

The 5'-flanking region of the rat vitamin D3 24-hydroxylase (P450cc24) gene was examined and a vitamin D-responsive element (VDRE) responsible for the 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) enhancement was identified. Unidirectional deletion analyses of the 5'-flanking region indicated that the region [-167/-102] is involved in vitamin D responsiveness. Further functional analyses showed that the segment [-204/-129] conferred the hormone responsiveness in an orientation-independent manner when it was placed upstream to the heterologous thymidine kinase promoter or the rabbit beta-globin promoter. The segment [-204/-129] contained two direct repeat motifs homologous to other VDREs found in the osteocalcin and osteopontin genes. Synthetic oligonucleotides containing the putative VDRE were used for functional analyses and gel mobility shift assays. The proximal [-151/-137], but not the distal [-169/-155] direct repeat activated the transcription in response to 1,25-(OH)2D3 through the beta-globin promoter. Furthermore, the proximal direct repeat formed a complex with the vitamin D receptor and a nuclear accessory factor(s) from COS cells (or retinoid X receptor) in the presence of 1,25-(OH)2D3. These results indicate that a direct repeat motif, AGGTGAgt-gAGGGCG, located at -151 base pairs upstream in the antisense strand binds to a heterologous dimer consisting of the VDR occupied with 1,25-(OH)2D3 and the nuclear accessory factor and that it plays a critical role in mediating the vitamin D enhancement of the rat P450cc24 gene expression.

Animals↗

Activation of the human osteocalcin gene by 24R,25-dihydroxyvitamin D3 occurs through the vitamin D receptor and the vitamin D-responsive element.

1 alpha-25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], together with vitamin D receptor (VDR), directly activates human osteocalcin (hOC) gene expression through a vitamin D-responsive element (VDRE) located in the promoter of the hOC gene. We investigated the effect of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] on the regulation of the hOC gene promoter and compared it with that of 1 alpha,25(OH)2D3. 24R,25(OH)2D3 did not activate the natural promoter in VDR-negative CV-1 cells. 24R,25(OH)2D3, however, induced the activation of this promoter following cotransfection with an hVDR expression vector. In VDR-positive MC3T3-E1 cells, 24R,25(OH)2D3 activated not only the natural hOC promoter but also a chimeric promoter composed of a synthetic hOC VDRE sequence linked to the thymidine kinase promoter. In combination with 1 alpha-25(OH)2D3, 24R,25(OH)2D3 did not exhibit any antagonist activity on the hOC promoter. These results suggest that under conditions of high 24R,25(OH)2D3 levels in vivo, this metabolite of vitamin D3 may activate hOC gene expression through receptor mechanisms identical to that for 1 alpha,25(OH)2D3.

Animals↗

Quantitative evaluation of tissue-specific cell adhesion at the level of a single cell pair.

Tissue specificity of cell adhesion was directly characterized in a unit cell interaction using a novel laser trapping cell manipulator in combination with a fixed micropipet. We quantified the adhesive specificity of endodermal and ectodermal epithelial cells from Hydra, which are known to sort out within hours after being dissociated and then randomly reaggregate. It was shown that homotypic pairs of cells from the same tissue source could adhere to each other within a certain period, while heterotypic pairs could not form an adhesion. It was also found that the adhesion probability was higher in endodermal epithelial cell pairs than in ectodermal epithelial cell pairs. The former pairs could adhere with a contact period of less than 30 sec, while 60% of the latter remained nonadherent even after a 6-min forced contact. The adhesive strength of the latter was estimated to be as large as 30 pN, while that of the former was much larger than 50 pN. The tissue-specific adhesivity quantitatively measured provides a new insight into the mechanism of cell sorting.

Animals↗

Pediatric spigelian hernia: reports of three cases.

We herein report three pediatric cases of spigelian hernia involving a 6-month-old girl, an 8-month-old girl, and a 3-year-old boy. This is a rare condition with only 20 children (12 boys and 8 girls) younger than 15 years of age previously reported in the literature. Their ages ranged from 6 days to 15 years. The hernia was situated on the right side in six cases, on the left side in nine, and was bilateral in four (with one case unreported). Among these, four cases were caused by trauma and one case by a postoperative complication. Our first and third cases were spontaneous, while the second case was a postoperative lateral ventral hernia. The first and second cases were associated with ipsilateral mediastinal neuroblastoma. No previous report of spigelian hernia has been associated with mediastinal neuroblastoma. We suspected that muscle atrophy caused by the neuropathy of the ninth to twelfth intercostal nerves may have been the cause of the hernia. These two cases are thus believed to be the first such cases to be reported.

Abdominal Injuries↗

Secondary correction of the bilateral cleft lip nose by excision of the columellar forked flap and nasal remodelling with reverse-U flaps: a preliminary report.

Although the forked flap procedure has been widely used as a technique to lengthen the columella in the bilateral cleft lip deformity, often the results are unfavourable. We describe a technique to achieve a more natural shape, in which the unsatisfactory forked flap is excised and the columella is reconstructed by mobilization and rotation of nasal skin, combined with bilateral reverse-U flaps. Five consecutive patients who underwent this secondary correction procedure are presented.

Adolescent↗

Effect of trimebutine maleate on the contractile response of the isolated ileum from diabetic rats.

1. Tension of the isolated ileum from diabetic rats induced by streptozotocin was measured isometrically to study the mode of action of trimebutine maleate (TMB). 2. The hyperreactivity of contractile response to KCl was observed in the isolated ileum from diabetic rats. TMB inhibited the contraction induced by KCl and acetylcholine (ACh) in normal solution. 3. In Ca2+ free solution, the hyperreactivity of contractile response to KCl was attenuated, and TMB did not inhibit the contraction induced by KCl. In contrast, TMB inhibited the contraction induced by ACh even in Ca2+ free solution. 4. These results suggest that the hyperreactivity of contractile response to KCl in the ileum from diabetic rats is due to the enhancement of Ca2+ influx through voltage-dependent Ca2+ channel and that TMB inhibits the hyperreactivity of contractile response through the inhibition of Ca2+ movement by the cell.

Animals↗

Purification and characterization of 3 alpha/beta-hydroxysteroid dehydrogenase from mature porcine testicular cytosol.

NADPH-dependent 3 alpha/beta-hydroxysteroid dehydrogenase (3 alpha/beta-HSD) was purified to apparent homogeneity from testicular cytosol of mature pigs. The purified enzyme catalyzes the conversion of 5 alpha-dihydrotestosterone (5 alpha-DHT) to both 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol. The molecular weight of the enzyme was estimated to be 31 kDa by SDS-polyacrylamide gel electrophoresis and 40 kDa by gel filtration chromatography indicating that the native 3 alpha/beta-HSD is a monomer. The isoelectric point of the purified enzyme was found to be 6.2 by density gradient isoelectric focusing and 6.4 by chromatofocusing. The enzyme reduced both 5 alpha- and 5 beta-DHT, 5 alpha- and 5 beta-dihydroprogesterone, 5 alpha- and 5 beta-dihydrocortisol, prostaglandin E2, 13,14-dihydro-15-keto-prostaglandin E2 and 13,14-dihydro-15-keto-prostaglandin F2 alpha. Moreover, the enzyme caused rapid reduction of other carbonyl compounds including aldehydes, ketones and quinones. The rates of reduction of these compounds are fast relative to the rates of reduction of steroids and prostaglandins. The purified enzyme was inhibited by AgNO3, SH-reagent, quercetin, hexesterol, stilbestrol, disulfiram and divalent cation such as Cu2+, Hg2+ and Cd2+. The two enzymes show certain similarities (e.g. molecular weight, cross-reactivity to a common antibody) and certain striking differences (e.g. pI, effects of various inhibitors and greater enzyme activity towards steroids (neonatal form) or prostaglandins (mature form). Reasons are give for suggesting that these enzymes are closely related to carbonyl reductase.

3-Hydroxysteroid Dehydrogenases↗

Calcium in pig livers following ischemia and reperfusion.

Calcium concentrations in pig livers were serially estimated following ischemia-reperfusion. Ischemia was produced by clamping the hepatic artery and the portal vein for 90 min (Group 1, n = 6) or for 180 min (Group 2, n = 6) during temporary side-to-side portacaval shunt performed before the induction of ischemia. Although there were no significant changes in hepatic calcium concentrations during ischemia, an immediate accumulation of calcium occurred 30 min after reperfusion in both groups. After these increases, the hepatic calcium concentration decreased to near the pre-ischemic level within 20 min in all animals in Group 1. The recovery of calcium was incomplete in Group 2. When the peak was defined as the highest level of calcium and the bottom as the lowest point after peak 60 min after reperfusion, the mean-peak was 11.0 +/- 1.3 (mean +/- SEM) nmol/mg dry weight liver in Group 1 and 12.8 +/- 1.4 nmol/mg dry weight liver in Group 2 (not significant). However, the mean-bottom in Group 1 was lower than that in Group 2 (5.5 +/- 0.3 and 8.1 +/- 0.8 nmol/mg dry weight liver, respectively, p < 0.05). These results indicate that hepatic calcium increases immediately after reperfusion and that recovery from this calcium accumulation seems to be a crucial factor for minimizing cellular injury.

Analysis of Variance↗

Effect of verapamil on hepatic reperfusion injury after prolonged ischemia in pigs.

This study investigated the effect of verapamil on prolonged and severe ischemic injury and elucidated the association of the calcium blocking action with cellular injury, assessing changes in hepatic calcium concentrations during ischemia and reperfusion in pigs. Hepatic ischemia was produced for 180 min by clamping both the hepatic artery and portal vein during temporary portacaval shunt performed before the induction of ischemia. Pigs were divided into two groups: the animals in the verapamil group (Group V, n = 6) received continuous administration of 0.025 mg/kg per min of verapamil intraportally for 20 min before ischemia. The control group (Group C) received nothing. A better survival rate was observed in Group V than in Group C (p < 0.01), but serum aspartate aminotransferase was higher in Group V after reperfusion (p < 0.05). There were no significant changes in hepatic calcium concentrations during ischemia in either group, but it increased immediately after reperfusion in both groups. However, no significant difference was found between the two groups. Recovery of the pyruvate/lactate ratio in Group V tended to be better after reperfusion compared to Group C (p = 0.08). These data suggest that the pre-ischemic administration of verapamil produced better survival in animals after prolonged normothermic ischemia. However, the reperfused liver suffered more severe damage in the first 6 h after reperfusion in the verapamil-treated animals. Moreover, there seemed to be very little blocking action of calcium influx. A reduced oxygen requirement may be involved in the protective action of verapamil on animal survival.

Animals↗

Changes in calcium content of the liver during hepatic ischemia-reperfusion in dogs.

Alteration of calcium metabolism in cells has been thought to be one of the main factors in ischemia-reperfusion injury. Serial changes in the tissue calcium content of the liver and the correlation between calcium level and liver injury were investigated. Experimental dogs were divided into two groups and subjected to hepatic ischemia of different duration: 60 min in Group A and 120 min in Group B, followed by reperfusion. Serum alanine aminotransferase, as an indicator of liver injury, was more elevated in Group B than in Group A. There was no change in hepatic calcium content during ischemia in either group. Immediately after reperfusion, there was no change in hepatic calcium level in Group A, whereas in Group B it was markedly elevated. The peak value occurred 30 min after reperfusion and gradually decreased thereafter, but did not return to pre-ischemic levels during the observation time. Plasma calcium concentrations in hepatic venous blood were markedly decreased in Group B 30 min and 60 min after reperfusion. These results suggest that calcium accumulation in the liver during the early reperfusion period may be one of the mediators of hepatic injury. To elucidate the mechanisms for elevation of calcium in hepatic tissue, serum malondialdehyde, a product of lipid peroxidation, was measured in hepatic venous blood. No elevation of serum malondialdehyde was observed in either group, indicating that the increases in calcium may not be due to oxidative stress. Serum mitochondrial aspartate aminotransferase and electron microscopic findings were used as indicators of mitochondrial injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

[Acidified aspirin-induced gastric lesion in rats with hepatic cirrhosis produced by N-nitrosodiethylamine or carbon tetrachloride. Effect of aldioxa on gastric lesions].

Gastric lesion was induced by the oral administration of acidified aspirin in rats with hepatic cirrhosis produced by N-nitrosodiethylamine (NDA) or carbon tetrachloride (CCl4). Gastric lesion by acidified aspirin was aggravated in NDA-induced cirrhosis, but not in CCl4-cirrhotic rats. To clarify this difference in the susceptibility of the gastric mucosa, gastric mucosal blood flow and gastric emptying were measured by the hydrogen gas clearance method and beads method, respectively. Gastric mucosal blood flow was lower and gastric emptying was significantly delayed in NDA-induced cirrhotic rats as compared with the controls, but not in CCl4-induced cirrhotic rats. Gastric mucosal blood flow in NDA-induced cirrhotic rats was significantly decreased by the oral administration of acidified aspirin as compared with the controls. Aldioxa dose-dependently inhibited the gastric lesion formation by acidified aspirin and inhibited the decrease of gastric mucosal blood flow in NDA-induced cirrhotic rats. These results suggest that aggravation of gastric lesion induced by acidified aspirin in NDA-induced cirrhotic rats would be due to the decrease of gastric mucosal blood flow and delay of gastric emptying. In addition, aldioxa showed a protective effect against gastric lesions induced by acidified aspirin in NDA-induced cirrhotic rats, suggesting that this compound would have an inhibitory effect on gastric lesions that are accompanied by hepatic cirrhosis.

Allantoin↗

[A 10-year field surveillance in Hinohara Village of Tokyo Prefecture from 1981 to 1990].

We conducted a surveillance to clarify the relationship between risk factors for diseases of adulthood and lifestyle in a Japanese rural community, Hinohara Village, a small village outside of Tokyo. The survey, carried out from 1981 to 1990 among residents aged 40 and over, comprised physical examination and blood chemistry with a questionnaire about dietary intake. Mean systolic blood pressure significantly decreased (p < 0.0001) from 140.9 mmHg in 1981 to 132.3 mmHg in 1990, whereas mean serum total cholesterol, mainly of male examinees, increased (p < 0.0001) from 181.4 mg/dl in 1981 to 191.7 mg/dl in 1990. Dietary salt intake significantly decreased (p < 0.0001) from 14.3 g/day in 1981 to 12.1 g/day in 1990. Adjusted mortality rate per 1,000 residents from cerebrovascular disease in this village decreased from 1.80 in 1981 to 0.50 in 1990. In contrast to its decline, the mortality rates from heart disease, bronchitis/pneumonia and neoplasms were 0.40, 0.35 and 0.55 in 1981 and increased to 1.25, 1.10 and 0.64 in 1990. The prevailing practice of maintaining a low-salt diet might cause the decrease of systolic blood pressure, which in turn was thought to decrease the mortality rate from cerebrovascular diseases. Although our previous study before 1981 suggested that total cholesterol was one of the preventive factors against cerebrovascular disease, in the present study a preventive effect of cholesterol was not substantiated. In contrast, cholesterol is a possible risk factor for ischemic heart disease. Thus, a changing pattern of risk factors of diseases of adulthood was observed in this village.

Adult↗

Site-directed mutagenesis of the Asp-197 and Asp-202 residues in chitinase A1 of Bacillus circulans WL-12.

The contribution of the Asp-197 and Asp-202 residues in chitinase A1 of Bacillus circulans WL-12 to the catalytic reaction was studied by site-directed mutagenesis of these residues. A kinetic analysis of the purified mutant chitinases suggests the involvement of both the Asp-197 and Asp-202 residues in the catalytic events of this enzyme, although the effects of mutations of Asp-197 were less severe than those of the other mutations.

Amino Acid Sequence↗

[A case of polyarteritis nodosa who developed rapidly progressive glomerulonephritis and presented with a tumor-like shadow on head CT in the remission stage].

A 70-year-old woman was admitted to our hospital because of weight loss, fever of unknown origin and rapid deterioration of renal function. Polyarteritis nodosa was diagnosed based on the findings of fever, weight loss, thrombocytosis, arthralgia and crescentic glomerulonephritis with vasculitis in the kidney biopsy specimens. Renal function progressively deteriorated and the patient underwent peritoneal dialysis (PD). Methylprednisolone pulse therapy and subsequent oral prednisolone (PSL) therapy combined with cyclophosphamide (CY) was instituted. Renal function gradually recovered and PD was discontinued 2 weeks later. She was discharged after about 2 months of hospitalization and received a monthly follow-up with daily administration of 10mg of PSL and 25mg of CY. Six months after discharge, PN activity was well controlled by PSL and CY, but mental disturbance gradually developed and head CT disclosed a low-density mass shadow that was enhanced with a ring-like appearance by contrast medium similar to a brain tumor. The follow-up CT did not show any enlargement of the mass shadow. One year later, the patient died of uremia and concomitant dementia. Autopsy disclosed cerebral infarct in the relevant site of the mass on CT and the healed stage of angitis in other tissues.

Acute Disease↗