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Biomedical subjects

K Sakurai

Publications and source records attributed to K Sakurai.

At least 19 recordsLinked to original sources

A novel non-peptide endothelin antagonist isolated from bayberry, Myrica cerifera.

A potent non-peptide ET receptor antagonist, myriceron caffeoyl ester (50-235), was isolated from the bayberry, Myrica cerifera. This compound selectively antagonized specific binding of [125I]ET-1, but not of [125I]ET-3, to rat cardiac membranes, ET-1-induced increase in the intracellular free calcium concentration in Swiss 3T3 fibroblasts, and ET-1-induced contraction of rat aortic strips. Thus, 50-235 is the first non-peptide ET(A) receptor antagonist. This compound can be useful for studying the physiological role of endothelin and exploring its role in various diseases.

3T3 Cells

Separation of diffusion and slow flow effects by use of flow rephasing and dephasing.

Spin-echo signal intensity alterations due to diffusion and slow flow are investigated in connection with modified Stejskal-Tanner pulse sequences for 2D Fourier MR imaging, one for flow rephasing and the other for flow dephasing gradient waveforms. The theoretical considerations and experimental results concerning the diffusion coefficient measurements of slowly flowing material by these sequences are summarized as follows: (a) By using the flow dephasing sequence with different diffusion and flow-sensitive gradients, slow flow effects can be distinguished from diffusion effects based on the quantitative difference between the diffusion- and flow-sensitive gradient amplitude dependences of these processes. (b) By using the combination of the flow rephasing and dephasing sequences with the same diffusion sensitivity, slow flow effects can be distinguished from diffusion effects directly based on their qualitative difference. By use of the latter approach, several in vivo images are also presented, which mainly represent macroscopic motions of spins, including slow flow such as tissue perfusion.

Acetone

Biodistribution of radiolabeled monoclonal antibody after intraperitoneal administration in nude mice with hepatic metastasis from human colon cancer.

The utility of the intraperitoneal (IP) administration of radiolabeled monoclonal antibody (mAb) for hepatic metastasis from human colon cancer was evaluated in congenital athymic mice. The intrasplenic injection of HT-29 LMM metastatic human colon cancer cell line reproducibly results in hepatic metastasis formation in nude mice. HT-29-15, a murine mAb of IgG1 class reactive with the HT-29 LMM cell line was labeled with iodine 125. One microgram/2 microCi of labeled HT-29-15 was injected intraperitoneally into mice with hepatic metastases, and additionally IP administration of the same dose of I-125 labeled HT-29-15 with increased volume and intravenous (IV) administration of dose quantity of HT-29-15 were performed. Blood samples were obtained at 1, 3, 5 hours, and the animals were sacrificed on days 1, 3, and 5. The percent of injected dose per gram (%ID/g) of blood after IP administration of I-125 labeled HT-29-15 reached the same level of %ID/g after IV administration by 5 hours. The transfer from the peritoneal cavity to blood was delayed by increasing the volume injected. From day 1 to day 3, there was a progressive increase for hepatic metastasis/blood ratios of I-125 labeled HT-29-15 in each group. There was no difference in the hepatic metastasis/blood ratios among the three groups. IP administration of specific mAb, therefore, provides the same level of tumor uptake in hepatic metastasis from colorectal cancer, and would be advantageous in patients with both hepatic metastasis and peritoneal implants in which radioimmunodetection and radioimmunotherapy are appropriate.

Animals

Sequence analysis of p-hydroxyphenyl-O-beta-D-xyloside initiated and radio-iodinated dermatan sulfate from skin fibroblasts.

To generate xyloside-primed dermatan sulfate suitable for sequence analysis, skin fibroblasts were incubated with p-hydroxyphenyl-beta-D-xylopyranoside and [3H]galactose, and free [3H]glycosaminoglycan chains were isolated from the culture medium by ion exchange and gel chromatography. After 125I labelling of their reducing-terminal hydroxyphenyl groups, chains were subjected to various chemical and enzymatic degradations, both partial and complete, followed by gradient polyacrylamide gel electrophoresis and autoradiographic identification of fragments extending from the labelled reducing-end to the point of cleavage. Results of periodate oxidation-alkaline scission indicated that the xylose moiety remained unsubstituted at C-2/C-3; exhaustive treatment with chondroitin AC-I lyase afforded the fragment delta HexA-Gal-Gal-Xyl-R (R = radio-iodinated hydroxyphenyl group), and complete degradations with chondroitin ABC lyase as well as testicular hyaluronidase yielded the fragments delta HexA/HexA-GalNAc-GlcA-Gal-Gal-Xyl-R with or without sulfate on the N-acetylgalactosamine. Partial digestions with testicular hyaluronidase or chondroitin B lyase indicated that glucuronic acid was common in the first three repeats after the linkage region and that iduronic acid could occupy any position thereafter. Hence, there were no indications of a repeated, periodic appearance of the clustered GlcA-GalNAc repeats which was previously observed in proteoglycan derived dermatan sulfate [Fransson L-A, Havsmark B, Silverberg I (1990) Biochem J 269:381-8], suggesting a role for the protein part in controlling the formation of particular copolymeric features during glycosaminoglycan assembly.

Carbohydrate Conformation

Development and characterization of Porphyromonas gingivalis-specific rat T-cell clones.

Porphyromonas gingivalis has been implicated as a major pathogen in periodontitis. To determine the role of T cells in the regulation of this disease, a method was developed for the generation and characterization of rat T-cell clones with antigen specificity to P. gingivalis whole cells. The clones studied so far demonstrated a T-helper (Th) phenotype W3/13+, W3/25+, OX8- and OX22-. These T-cell clones proliferated in vitro in response to P. gingivalis, but not to other bacteria (Prevotella intermedia, Actinobacillus actinomycetemcomitans, Wolinella recta, Fusobacterium nucleatum, Streptococcus sanguis). Limiting dilution analysis showed W3/25+, OX8- T cells preferentially respond to P. gingivalis, rather than W3/25-, OX8+ T cells. P. gingivalis-reactive W3/25+ T cells belonged to the OX22- population, suggesting that the OX22- T cells may represent memory cells. All clones tested produced interferon gamma, but not interleukin 2. The cloned T-cell F1 significantly enhanced P. gingivalis-specific antibody production (p < 0.03). The availability of these cloned T cells should bring new insight into the mechanism by which T cells regulate oral health and periodontal disease.

Animals

Effect of glutathione on lambda deoxyribonucleic acid strand breaks in the reaction system of glutathione-alloxan in the presence of Fe(3+)-ethylenediaminetetraacetic acid.

Alkaline sucrose density gradient and agarose gel electrophoresis methods were used to observe lambda deoxyribonucleic acid (DNA) strand breaks by the reaction system of reduced glutathione (GSH) with alloxan in the presence of Fe(3+)-ethylenediaminetetraacetic acid (EDTA). When DNA was incubated in the reaction system for 10 min, DNA strand breaks were easily induced. The increasing concentrations of GSH up to 1.0 mM in the reaction system in the presence of 1.0 mM alloxan caused DNA strand breaks in a concentration-dependent fashion and GSH beyond 2.0 mM caused in the strand breaks of DNA by which the fragments with multiple ranges of molecular weight were produced. The strand breaks of DNA in the reaction system containing low concentrations of GSH were protected by catalase and hydroxyl radical (HO.) scavengers but superoxide dismutase (SOD) did not, indicating that such breaks were induced by HO.generated from the Fenton reaction. On the other hand, the strand breaks of DNA at high concentrations of GSH were protected by ethanol and desferrioxamine, but not effectively by SOD and HO.scavengers, suggesting the possible participation of some oxidizing species of iron rather than HO.. These results indicate that HO.or oxidizing species of iron generated in the GSH-alloxan system depending on the concentration of GSH attacks DNA to produce strand breaks.

Alloxan

Enzymatic generation of alloxan radicals in rat liver microsomes: possible participation of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P-450 reductase.

Electron spin resonance studies showed that addition of rat liver microsomes to the reaction system of alloxan with reduced nicotinamide adenine dinucleotide phosphate (NADPH) resulted in a marked increase in the generation of alloxan radicals (AH.), whereas heat-denatured microsomes were without such effect. Oxidation of NADPH by alloxan was also stimulated by microsomes. The microsomes from rats treated with phenobarbital, an inducer of cytochrome P-450 reductase, greatly stimulated both the AH.generation and the NADPH oxidation. However, the microsomes from rats treated with 3-methylcholanthrene, an inducer of DT-diaphorase, did not have stimulative effect greater than the control microsomes. These results suggest the possibility that NADPH-linked AH.generations in microsomal membranes is catalyzed by NADPH-cytochrome P-450 reductase.

Alloxan

Use of two miniplates for intermaxillary skeletal fixation in the treatment of jaw deformity and fracture.

Special techniques of skeletal intermaxillary fixation are described, which may be used in edentulous patients or those with many missing teeth or multiple fractures of the jaw. Two such cases are described in which the usual fixation techniques could not provide sufficient stabilization because of linguoversion and mesioversion or lack of teeth, resulting in inability to maintain a vertical interocclusal relationship. Two long eight-hole Champy miniplates were therefore used distally to the canines on both sides. In the first case, they provided fixation following a sagittal ramus osteotomy to advance the mandible, and in the second case they were used in the treatment of a mandibular fracture.

Adult

Therapeutic effects of oral rebamipide and in combination with cimetidine on experimental gastritis in rats.

The present study evaluated the therapeutic effects of rebamipide alone and in combination with cimetidine on experimental gastritis established by the administration of 5 mM sodium taurocholate (TCA) for 6 months in rats. Morphological and biochemical analyses were performed to determine the effects of rebamipide, administered alone or in combination with cimetidine, on chronic, atrophic and erosive gastritis. Rebamipide and cimetidine were administered to rats as a dietary admixture for 4 weeks after withdrawal of TCA. Rebamipide dose-dependently reduced the total length of the erosion, normalized the mucosal thickness and increased the number of parietal and total cells, and tended to reduce interstitial infiltration of inflammatory cells and proliferation of collagenous fibers. Moreover, histochemical and biochemical studies also showed rebamipide to be effective. Rebamipide increased the PAS-positive mucus and normalized the reduced gastric mucosal SOD activity. The therapeutic effect of rebamipide on the experimental gastritis was enhanced by the combined use of cimetidine. These results suggest that rebamipide has a therapeutic effect on chronic atrophic erosive gastritis induced by TCA, and that the mechanism of the therapeutic effect is partially due to the increase in PAS-positive mucus and gastric mucosal SOD activity. Furthermore, the enhanced effect of the combination therapy of rebamipide with cimetidine was considered to be due to the actions of both cimetidine and rebamipide.

Administration, Oral

[IgM HCV antibody in chronic hepatitis and liver cirrhosis].

To evaluate the role of IgM specific antibody in the diagnosis and monitoring of the patients with chronic hepatitis C, sera from 114 cases with chronic hepatitis C and liver cirrhosis were tested. IgM antibody to hepatitis C virus was detected in 40.0% of CAH, as compared with 21.4% of CIH, 17.4% of LC, 20.0% of LC with HCC. IgM antibody was also detectable in cases with high level of s-ALT. Patients with positive this antibody have high titer of IgG antibody to hepatitis C virus. In summary, testing for this antibody may be useful to evaluate the recurrence or disease activity and may also be helpful in IFN therapy.

Adult

[Extraction efficacy on uptake of intraportally injected monoclonal antibody by human colorectal metastases in nude mice].

Route of administration is an important determinant in tumor uptake of monoclonal antibody (mAb). We studied the extraction efficacy of intraportal injection (IP) on tumor uptake over time in hepatic metastases of human colon carcinoma (HT-29LMM) in nude mice. H-15, a murine IgG1 mAb reactive with HT-29LMM was labeled with I-125, and injected at dose of 0.1 microgram and 1.0 microgram intraportally (IP) or intravenously (IV). More than 3 animals per group were sacrificed immediately, 1 h, 24 h, 72 h, and 120 h following injection. Hepatic metastases, normal liver tissue, and blood were weighted and counted for radioactivity. Compared to IV, IP injection resulted in higher (P less than 0.01) percent injection dose per gram (%ID/g) in metastases at all time points for both doses. Metastases: blood and metastases: liver uptake ratios were higher (P less than 0.05) on day 3 and 5 for both IP doses compared to IV doses. Significant improvement in tumor uptake was seen following IP injection of specific mAb; this has important implications on the design of clinical trials using mAb.

Animals

[Elimination of Japanese cedar (Cryptomeria japonica) aeropollen by rainfall].

The concentration of aeropollens of Japanese cedar decreases on rainy days, due to the rainfall removing pollens from the atmosphere. An analysis was performed of the concentration of pollen grains in rain water samples from Yokohama during the period February 10 to April 30, 1991. Sampling of rain water was performed using an automatic rain water collector, and an analysis performed on each mm of rainfall, from 1 mm to 5 mm. In this collector, 1 mm of rainfall corresponds to 100 ml of accumulated rain water. The pollens in rain water were concentrated by centrifugation to 1/200 volume, and pollen grain count was performed on a Fuchs. Rosenthal hemocytometer. Pollens of Japanese cedar were detected in the rain water during the period, 22 February to 19 April, and peaked on 22 March. The number of pollens at peak was 264,000 grains per 100 ml. The pollen count contained in the 2nd to 5th mm of rainfall compared to that in the first mm of rainwater was 19.4% in the 2nd mm of rainfall, 6.7% in the 3rd, 4.4% in the 4th and 2.3% in the 5th. From a log-log graph plot of this data, a regression line was obtained for a regression equation, y = 100.x-2.29. These data indicate that rainfall quickly clears pollens of Japanese cedar from the atmosphere. Examination of pollen obtained from the rain water, showed a few % of the pollen grains had ruptured, and on the surface of the cytoplasmic membrane of the ruptured pollen were attached suspended particulate matters from atmosphere.

Air Pollution

A cylinder-shaped balloon catheter for the management of dissecting aneurysms in acute stage.

We developed a new procedure to close the entry of dissecting aneurysm in acute stage with a specially designed cylinder-shaped balloon catheter. The balloon catheter consists of 7F double lumen catheter and a silicone rubber balloon at the tip. The balloon has a central tube 14 mm caliber made of rigid silicone and it inflates into the shape of a cylinder with an injected solution. The central tube serves as a route for maintaining the aortic blood flow to the distal site. The catheter with a deflated balloon is inserted into the thoracic aorta ascendingly through a 14 or 16 mm caliber Dacron vascular graft sutured at the side of the distal aorta in a similar manner to intra-aortic balloon pumping. The tip of the catheter is carried to the entry tear of the pseudo-lumen. Then the cylinder-shaped balloon is inflated with solution. The entry is, therefore, closed with the side wall of the balloon and the blood stream into the dissected lumen is occluded while maintaining an aortic blood flow to the distal site. To prevent any possible occlusion due to thrombosis, some type of anticoagulant is administered via the catheter connected to a continuous injector. The healing process of the dissected lumen can be enhanced by injecting some type of coagulant directly into the lumen. The treatment is completed when the blood in the false lumen coagulates and stabilizes. The cylinder-shaped balloon is then deflated and the catheter withdrawn. The graft is removed and the stump is sutured.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

[A case of congenital cystic adenomatoid malformation of the lung in 18-year-old male].

A case of congenital cystic adenomatoid malformation (CCAM) of the lung is reported. The patient had recurrent pneumonia after the second day of delivery, and was admitted to our hospital, at the age of 18. He received right pneumonectomy under the diagnosis of CCAM. The resected lung was composed of multiple cysts with thin wall measuring 20-30 mm in diameter. Microscopic examination showed that the cyst wall was lined by ciliated columnar epithelium, and infiltration of chronic inflammatory cells was found in the submucosal layer. Bronchial cartilage was absent through the specimen. These microscopic findings are identical with those of CCAM, which is very rare in this age.

Adolescent

Carcinoid tumor of the lung: clinicopathological study of 32 cases.

A retrospective study was conducted on 32 patients who had had bronchial carcinoid tumors between 1965 and 1989. The average age of the patients was 48.5 years, with a male to female ratio of 3.6:1. Of the 32 patients, 28 were diagnosed pathologically to have typical bronchial carcinoid tumors and the other four, atypical bronchial carcinoid tumors. Twenty-two of the 28 typical bronchial carcinoid tumors were classified as stage I, but only one of the four atypical bronchial carcinoid tumors was at stage I. Two typical carcinoid tumor patients and two atypical carcinoid tumor patients were found, pathologically, to have lymph node metastasis. The typical carcinoid tumors showed a more significant endobronchial polypoid growth than the atypical carcinoid tumors (P = 0.0138). The five-year-survival rate was 100% in patients with typical carcinoid tumors and 25% in those with atypical carcinoid tumors. The difference between the five-year-survival rate for the typical carcinoid and atypical carcinoid patients was statistically significant (P = 0.001).

Adult