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Biomedical subjects

S Shimizu

Publications and source records attributed to S Shimizu.

At least 469 records · Page 26Linked to original sources
PubMed1996

Detection of ultraviolet photoproducts in mouse skin exposed to natural sunlight.

In the present study, we for the first time investigated the formation of ultraviolet (UV) photoproducts, cyclobutane pyrimidine dimers (CPDs), pyrimidine-pyrimidone (6-4) photoproducts (64PPs) and Dewar isomers, in vivo in shaved and depilated C3H/HeN mouse skin exposed to natural sunlight (NSL) at noon for 5 min to 1 h in mid-summer, using a highly sensitive immunohistochemical method. This method permits the quantitative analysis of UV-photoproducts in formalin-fixed, paraffinembedded sections with specific antibodies against CPDs, 64PPs and Dewar isomers. We demonstrated that the induction of CPDs in vivo in mouse skin by NSL was exposure time-dependent, but the accumulation of 64PPs or Dewar isomers was comparatively low in the skin sections from mice exposed to NSL in vivo. The results indicate that CPDs are the main photoproducts in vivo induced by sunlight and that their formation and repair may be important in connection with carcinogenesis in sun-exposed areas of human skin.

Animals↗
PubMed1996

Mutational analysis of the p53 and K-ras genes and allelotype study of the Rb-1 gene for investigating the pathogenesis of combined hapatocellular-cholangiocellular carcinomas.

Because combined hepatocellular-cholangiocellular carcinoma is rare and its biological features and pathogenesis have not been well established, we investigated alterations of the p53, K-ras and Rb-1 genes, as well as expression patterns of carcinoembryonic antigen and keratin, in seven combined hepatocellular-cholangiocarcinomas out of 557 hepatocellular carcinomas autopsied at Tokyo University during 30 years. Mutations of the p53 gene were found in two cases, at codon 244 (GGC to TGC) in the cholangiocellular carcinoma component of case 1 (mixed type, showing an intimate intermingling of both elements) and at codon 234 (TAC to AAC) in both components of case 5 (combined type, consisting of contiguous but independent masses of both elements). Mutation of the K-ras gene (codon 12, GGT to GAT) was seen only in the cholangiocellular carcinoma component of clinically apparent double cancer, case 6. Allelic alteration of the Rb-1 gene was observed in two cases, deletion of both alleles in the hepatocellular carcinoma component of case 3 (combined type) and replication error of the same pattern in both components of case 4 (mixed type). Immunohistochemical analysis showed that the hepatocellular carcinoma components of five cases (cases 2, 3, 5, 6, 7) were immunoreactive for keratin, suggesting biliary epithelial transformation. In four of the five cases (cases 3 and 5 combined, case 7 mixed and case 6 double cancer), cholangiocellular carcinoma components were also positive for keratin. These results suggest that both components of combined hepatocellular-cholangiocarcinoma have the same genetic and phenotypic character and might have arisen from the same origin in some cases.

Aged↗
PubMed1996

Establishment and characterization of three androgen-independent, metastatic carcinoma cell lines from 3,2'-dimethyl-4-aminobiphenyl-induced prostatic tumors in F344 rats.

Three stable carcinoma cell lines, designated PLS10, PLS20 and PLS30, have been established from 3,2'-dimethyl-4aminobiphenyl plus testosterone-induced carcinomas in the dorsolateral prostate of male F344 rats. The cells are keratin-positive and grow as typical epithelial monolayers in culture. When injected into intact male nude mice, PLS10 and PLS30 cells form well-differentiated adenocarcinomas with abundant connective tissue stroma, while PLS20 cells give rise to poorly differentiated adenocarcinomas. Growth of all PLS cell lines in nude mice is not affected by castration and the cells are immunohistochemically negative for androgen receptors. Tumor growth rates in nude mice were found to be PLS20 > PLS10 > PLS30, with significant in vitro stimulation by insulin/transferrin, but not epidermal growth factor, dexamethasone or basic fibroblast growth factor. Spontaneous lung metastases were observed in all cases. However, skeletal invasion including bone is essentially observed only with the PLS20 tumors. Gelatin zymography showed predominant secretion of the active form of gelatinase B (Mr 92,000 type IV collagenase) by all the cell lines. Karyotype analysis revealed PLS10, PLS30 and PLS20 to be diploid, hyperdiploid and hypertetraploid, respectively. The results demonstrate that the three PLS cell lines are androgen-independent and metastatic in common, but have different histology, growth potential and invasiveness. They may therefore be useful models for understanding progression and metastasis of human prostatic carcinomas.

Aminobiphenyl Compounds↗
PubMed1996

Development of a potassium-specific adsorbent for direct hemoperfusion.

Direct hemoperfusion (DHP) over an exchange resin for sodium is capable of rapidly lowering an elevated serum potassium level but has not been used clinically because of subsequent electrolyte abnormalities. After the completion of detailed in vitro studies, we developed a sodium/calcium/magnesium exchange resin mixture specifically to remove potassium from the blood. The mixture, which consisted of exchange resins for sodium (48%), calcium (48%), and magnesium (4%), gave the most satisfactory results in vitro. DHP through these resin-mixture columns for 2 h reduced elevated plasma potassium levels (6.7 +/- 1.1 to 3.5 +/- 0.6 mEq/L, p < 0.001) in anephric dogs without including any significant change in the levels of sodium, calcium, magnesium, albumin, total protein, or cholesterol. The platelet losses and changes in the plasma free hemoglobin levels observed were similar to those found with activated charcoal hemoperfusion. These results suggest that this resin hemoperfusion may be useful in patients with acute hyperkalemia.

Animals↗
PubMed1996

In vitro studies on a new method for islet microencapsulation using a thermoreversible gelation polymer, N-isopropylacrylamide-based copolymer.

Various materials for the semipermeable membrane for microencapsulation of islets, such as alginate complex and agarose, have been used. In this study, a thermoreversible gelation polymer, N-isopropylacrylamide based copolymer was used to make microencapsulated islets and was examined in vitro. The polymer has little or no cytotoxicity for human dermal fibroblasts. The characteristics of viscoelasticity below the soluble gel transition temperature (SGTT) and of thermoreversibility, the water soluble polymer below the SGTT (22 degrees C) becoming water insoluble upon heating, contributed to simplifying the encapsulation technique. We obtained viable islets at the center of the membrane with a thickness of approximately 20-50 microns, accounting for a 40% yield of encapsulated islets. Static glucose challenge test with microencapsulated islets revealed the insulin response to the concentration of glucose. The insulin concentrations of the culture medium in the microencapsulated islet group were the same as those in a similar free islet group up to 42 days. These results indicate that the morphological and functional stability of the new method for microencapsulation may be sufficient for it to be used for transplantation in diabetic animals.

Acrylamides↗
PubMed1996

Proposal of a new auditory nerve stimulation method for cochlear prosthesis.

The stimulation electrodes of cochlear implants are covered by a lymph liquid with high electrical conductivity, which causes the transmitted information to be reduced by channel interaction. Even if this problem were solved, the stimulation regions may be discrete; therefore, there may be regions in which the electrode array cannot stimulate selectively. To solve these problems, we proposed a new auditory nerve stimulation method which we call the tripolar electrode stimulation method for cochlear implants. Our method stimulates using 3 adjacent electrodes selected from among the electrodes of the electrode array. The center electrode receives the currents emitted from the electrodes on both sides. We conducted animal experiments using this method. On the basis of the results we obtained, we concluded that our method may succeed in narrowing the stimulation region and continuously moving the stimulation site.

Animals↗
PubMed1996

[Clinical study on bacteremia in patients with liver cirrhosis].

Infections and fever are frequent in patients with liver cirrhosis. Study on bacteremia in cirrhotic patients has not been reported in Japan. In a 16 year period from 1979 to 1994, we collected 39 cases with 40 episodes and 44 microorganisms of bacteremia for this study. The incidence of bacteremia in cirrhotic hospital admissions was 4.8% (39/808). Gram negative bacteria were the predominant microorganisms of bacteremia (66%, 29/44). Among them, Escherichia coli, Klebsiella pneumoniae, Vibrio sp. were the three most commonly detected microorganisms. Pseudomonas aeruginosa bacteremia has not been detected. Laboratory data of cirrhotic patients showed that positive blood culture patients had significantly lower serum albumin, prothrombin time and hepaplastin test than negative patients. Focal infection could be diagnosed in only 45% (20/44). The mortality rate was 28% (11/39), but the bacteremia related death (by septic shock) were only 2 cases. The other causes of death were hepatic failure in 9 cases. In conclusion, bacteremia is a important complication of liver cirrhosis. Blood culture is necessary in cirrhotic patients with fever.

Adult↗
PubMed1996

Novel Metabolic Transformation Pathway for Cyclic Imides in Blastobacter sp. Strain A17p-4.

The metabolic transformation pathway for cyclic imides in microorganisms was studied in Blastobacter sp. strain A17p-4. This novel pathway involves, in turn, hydrolytic ring opening of a cyclic imide to yield a monoamidated dicarboxylate, hydrolytic deamidation of the monoamidated dicarboxylate to yield a dicarboxylate, and dicarboxylate transformation similar to that in the tricarboxylic acid cycle. The initial step is catalyzed by a novel enzyme, imidase. Imidase and subsequent enzymes involved in this metabolic pathway are induced by some cyclic imides, such as succinimide and glutarimide. Induced cells metabolize various cyclic imides.

Journal Article↗
PubMed1996

Cloning of the aldehyde reductase gene from a red yeast, Sporobolomyces salmonicolor, and characterization of the gene and its product.

An NADPH-dependent aldehyde reductase (ALR) isolated from a red yeast, Sporobolomyces salmonicolor, catalyzes the reduction of a variety of carbonyl compounds. To investigate its primary structure, we cloned and sequenced the cDNA coding for ALR. The aldehyde reductase gene (ALR) comprises 969 bp and encodes a polypeptide of 35,232 Da. The deduced amino acid sequence showed a high degree of similarity to other members of the aldo-keto reductase superfamily. Analysis of the genomic DNA sequence indicated that the ALR gene was interrupted by six introns (two in the 5' noncoding region and four in the coding region). Southern hybridization analysis of the genomic DNA from S. salmonicolor indicated that there was one copy of the gene. The ALR gene was expressed in Escherichia coli under the control of the tac promoter. The enzyme expressed in E. coli was purified to homogeneity and showed the same catalytic properties as did the enzyme from S. salmonicolor.

Alcohol Oxidoreductases↗
PubMed1996

Involvement of ICE family proteases in apoptosis induced by reoxygenation of hypoxic hepatocytes.

Cell death due to reoxygenation after hypoxia was characterized in primary cultured hepatocytes. Fluorescence and electron microscopic analyses of reoxygenated hepatocytes revealed morphological characteristics of apoptosis, including chromatin condensation, nuclear fragmentation, and formation of apoptotic bodies. Few necrotic hepatocytes, defined by loss of plasma membrane integrity, mitochondrial swelling, and formation of large vacuoles, were observed. Activation of interleukin-1 beta-converting enzyme (ICE)-like and CPP32/Yama-like proteases, which are known to drive apoptosis, was observed during reoxygenation, and addition of their respective inhibitors inhibited the induction of apoptosis, indicating the involvement of ICE family proteases in apoptosis by reoxygenation. Production of oxygen radicals was enhanced by reoxygenation of hypoxic cells, and reoxygenation-induced apoptosis was inhibited by oxygen radical scavengers, suggesting a role for reactive oxygen species as a triggering factor in cell death. Electrophoretic analysis revealed the presence of 50-kb DNA fragments but not oligonucleosomal DNA fragments in reoxygenation-induced apoptotic hepatocytes.

Animals↗
PubMed1996

Flow-dependent influence of high-O2-affinity erythrocytes on peak VO2 in exercising muscle in situ.

To evaluate the influence of a high-O2 affinity of the erythrocyte and of flow rate on muscle's ability to extract O2 and develop force, we perfused dog gastrocnemius contracting isometrically at 4 Hz with normal-O2-affinity perfusate or high-O2-affinity perfusate at high and moderate flows (200 and 100 ml . min-1 . 100g-1, respectively). High-O2-affinity perfusate was prepared by incubating human citrate-phosphate-dextrose-stored erythrocytes with buffered saline containing cyanate (4 degrees C, 18 h) and normal-affinity perfusate by storing 2,3-diphosphoglycerate-rejuvenated erythrocytes in the same solution without cyanate. PO2 when blood is half oxygenated was 30.6 Torr for normal perfusate and 18.1 Torr for high-affinity perfusate. During 4-Hz stimulation, the tension developed by the muscle increased incrementally (positive staircase) to reach a peak value after 1.2-1.6 min for the normal perfusate and 0.6-0.7 min for the high-affinity perfusate (P < 0.05). The rate of decline during the early fatigue (measured from the onset of tension decline to 3 min) with high-affinity perfusate was significantly faster than it was with normal perfusate (P < 0.05). These findings suggest that both the staircase effect and the early fatigue are related to O2 availability, which is restricted when erythrocytes have a high O2 affinity. The peak O2 uptake values measured at 3 and 5 min were significantly lower (by 14-24%) with high-affinity perfusate than with normal perfusate at a given level of O2 delivery (arterial O2 content x flow) (P < 0.05). PO2 of venous effluent was proportionally related to peak O2 uptake. The present results indicate that neither blood flow nor O2 delivery is the sole determinant of the muscle's ability to extract O2.

Animals↗
PubMed1996

Immunohistochemical study of mixed tumor of the skin with marked ossification.

We observed an unusual case of mixed tumor of the skin associated with marked ossification on the upper lip of a 68-year-old Japanese woman. The tumor was a well-circumscribed mass that measured 3 x 3 x 2 cm and contained exuberant bone formation with a marrow-like structure. Histological examination of the tumor showed that the bones occupied a quarter of the specimen. Except for the large bone formation, the tumor showed typical features of a tubulocystic type of mixed tumor. The bone was formed without intervening cartilage, suggesting the possibility of the direct deposition of osteoid by metaplastic cells. To our knowledge, no similar case of mixed tumor of the skin associated with marked bone formation has been reported.

Adenoma, Pleomorphic↗
PubMed1996

Cefotiam-induced contact urticaria syndrome: an occupational condition in Japanese nurses.

A case of occupational contact urticaria syndrome caused by cefotiam dihydrochloride (CTM) in a Japanese nurse is reported. The patient had become sensitized to CTM through the process of preparing antibiotics 8 months before she developed symptoms. A review of the literature revealed 13 similar cases, all involving Japanese nurses, reported since CTM became available in Japan.

Adult↗
PubMed1996

Acyclothymidine alleviates intestinal toxicity of 5'-deoxy-5-fluorouridine without loss of antitumor activity in mice.

To reduce the intestinal toxicity of orally administered 5'-deoxy-5-fluorouridine (5'-DFUR) in mice, we co-administered 5'-DFUR with acyclothymidine [AcyT, 5-methyl-(2'-hydroxyethoxymethyl) uracil], a potent inhibitor of pyrimidine nucleoside phosphorylase (PyNPase). Orally administered 5'-DFUR alone caused intestinal toxicity and severe damage to the intestinal villi, while 5'-DFUR with AcyT reduced the intestinal toxicity, and prevented damage to the intestinal villi. This toxicity arising from orally administered 5'-DFUR could not be reduced by intravenous administration of AcyT, but was alleviated by oral administration. Orally co-administered AcyT showed little effect on antitumor activity of 5'-DFUR toward subcutaneously implanted Lewis lung carcinoma, though the intestinal toxicity was reduced in the tumor-bearing mice. This finding suggests that orally co-administered AcyT may prevent the undesirable conversion of 5'-DFUR to 5-FU by PyNPase during the process of absorption in the intestinal tract.

Administration, Oral↗
PubMed1996

Modulation of the pharmacokinetics of 5'-deoxy-5-fluorouridine and 5-fluorouracil in rats by oral co-administration of acyclothymidine.

The effect of an inhibitor of pyrimidine nucleoside phosphorylase (PyNPase), acyclothymidine (AcyT), on the pharmacokinetics of 5'-deoxy-5-fluorouridine (5'-DFUR) and 5-fluorouracil (5-FU) was investigated in an oral co-administration of 5'-DFUR and AcyT in rats. AcyT increased the maximal plasma concentration (Cmax) and apparent absorption rate constant (ka) of 5'-DFUR, as expected, but the increase in AUC (area under the curve) was not significant. It was expected that AcyT would only inhibit the phosphorolytic degradation of 5'-DFUR to 5-FU, but the effect was more evident on the pharmacokinetic parameters of 5-FU than on those of 5'-DFUR. AcyT also increased AUC and Cmax of 5-FU when orally co-administered with 5-FU. An inhibitory effect of AcyT on the enzymatic degradation of 5-FU in rat liver and intestinal extract was investigated. AcyT inhibited the degradation in intestinal extract but not in the liver. The result suggests that orally administered AcyT affects the pharmacokinetics of 5-FU partly by inhibiting 5-FU degradation in the process of intestinal absorption as well as by acting as an inhibitor of PyNPase.

Administration, Oral↗
PubMed1996

Inhibition of rat liver microsomal desaturases by curcumin and related compounds.

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) inhibited noncompetitively rat liver microsomal delta 5 desaturase (Ki = 36 microM) and delta 6 desaturase (Ki = 28 microM). Although curcumin has a symmetrical structure with a methylene group as the center, only half the structure is essential for the desaturase inhibition. The structure necessary for the inhibition is similar to that of alkyl gallate (H. Kawashima et al., Biochim. Biophys. Acta, in press), i.e., a 3-hydroxy group of the aromatic ring is essential for the inhibition and a free carboxyl group at the end opposite to the aromatic ring interferes with the inhibitory effect. The following structural features of curcumin are necessary for the desaturase inhibition: (i) the aromatic ring conjugated with the double bond between the 1 and 2 (or 6 and 7) positions; (ii) both 4-hydroxy and 3-methoxy groups (for both desaturase inhibitions); and (iii) only a 4-hydroxy group (for delta 6 desaturase inhibition).

Animals↗
PubMed1996

Nicardipine and nifedipine inhibit fatty acid desaturases in rat liver microsomes.

Nicardipine and nifedipine, Ca channel blockers, inhibited rat liver microsomal desaturases, though verapamil, methoxyverapamil, cinnarizine, flunarizine, and diltiazem did not. However, nicardipine and nefidipine apparently did not inhibit the fungal desaturation in Mortierella alpina 1S-4. Nicardipine inhibited rat liver microsomal delta 5 desaturase specifically (50% inhibitory concentration. 170 microM), and nifedipine inhibited delta 6 desaturase specifically (78 microM). The inhibition by nicardipine and nifedipine is uncompetitive, the Ki values for delta 5 and delta 6 desaturases being 62 and 44 microM, respectively.

Animals↗