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Biomedical subjects

M Sasaki

Publications and source records attributed to M Sasaki.

At least 235 records · Page 13Linked to original sources

Biodistribution and breast tumor uptake of 16alpha-[18F]-fluoro-17beta-estradiol in rat.

To evaluate the usefulness of 16alpha-[18F]-fluoro-17beta-estradiol (FES) for the assessment of estrogen receptor (ER), we examined the tissue distribution and kinetics of FES in immature female Sprague-Dawley rats and then examined FES uptake in rat breast tumors induced by 7,12-dimethylbenz(a) anthracene (DMBA). The FES uptake by the uterus, an ER-rich tissue, was highly selective and it was 3.34 +/- 0.79%ID/g at 60 minutes and 1.57 +/- 0.57%ID/g at 120 minutes after injection. The FES uptakes in ER-negative tissues were 0.12 +/- 0.05%ID/g or less and 0.05 +/- 0.03%ID/g or less, respectively. Coadministration of unlabeled beta-estradiol showed marked depression of uterine FES uptake. The FES uptake by rat breast tumors was 0.14 +/- 0.06%ID/g at 60 min and 0.12 +/- 0.09%ID/g at 120 min. The FES uptake by rat breast tumors correlated with the ER concentration (r = 0.45, p < 0.05). In conclusion, these results suggest that the FES uptake by tissue is mainly ER mediated and FES is thus useful for detecting ER positive breast tumors.

9,10-Dimethyl-1,2-benzanthracene↗

Pneumocephalus associated with aqueductal stenosis: three-dimensional computed tomographic demonstration of skull-base defects.

Ventriculoperitoneal (VP) shunt placement in patients with aqueductal stenosis has recently been reported as a cause of pneumocephalus. We report on a patient with pneumocephalus associated with aqueductal stenosis treated by VP shunting. A 29-year-old woman who had undergone a shunt operation for aqueductal stenosis 7 years previously sustained a whiplash injury in a minor traffic accident. Computed tomography (CT) revealed massive subdural pneumocephalus, and three-dimensional reconstructions of CT images clearly demonstrated defects in the skull base overlying the ethmoid sinuses. Both endoscopic III ventriculostomy and placement of external ventricular drainage were came free of symptoms and rhinorrhea ceased. Three-dimensionally reconstructed CT images were useful in detecting the extent of the patient's skull base defect. III Ventriculostomy was not effective in this case. Direct closure of the skull base by craniotomy was not necessary, and a programmable valve system was effective in preventing recurrence of either pneumocephalus or rhinorrhea.

Adult↗

A diagnostic method for suspected Alzheimer's disease using H(2)15O positron emission tomography perfusion Z score.

We developed cerebral perfusion Z score map (Z map) images using H(2)15O and positron emission tomography (PET), and examined their use in diagnosing Alzheimer's disease (AD). Cerebral blood flow (CBF) images were obtained using the PET and H(2)15O autoradiographic method. The best region for normalising the CBF value to remove individual variantion was determined. Then CBF images were transformed to Talairach's standard space, and each pixel value of an individual's image set was normalized to the mean value of the sensorimotor area. Based on the CBF images of 20 normal volunteers, normative mean and standard deviation (SD) CBF images were constructed. Then, each pixel value of the axial CBF images in 28 patients with probable AD and 10 further normal volunteers was converted to a Z score (Z = [normal mean--individual value]/normal SD). A Z map, showing pixels exceeding a threshold of Z score > 2 on MRI of standardised anatomical space was demonstrated. These 38 Z maps were interpreted by four radiologists. When regions in the temporoparietal area were found with Z scores > 2, the subject was diagnosed as having AD. A receiver operating characteristic (ROC) analysis was performed to compare the conventional CBF images and Z maps. The diagnostic performance of the Z map was superior to that of visual inspection of conventional CBF images (mean areas under the ROC curve of the four radiologists were 0.946 and 0.584, respectively). These results indicate that a Z map obtained in this way is superior to conventional PET for diagnosing AD.

Aged↗

Molecular cloning and linkage analysis of complement C3 and C4 genes of the Japanese medaka fish.

The thioester-containing complement components, C3 and C4, are believed to have arisen by gene duplication from a common ancestor, and the mammalian C4 gene resides in the vicinity of the C2 and B genes within the major histocompatibility complex (MHC) class III region. To analyze the evolution of both the complement system and the MHC, we determined the complete primary structures of two C3 genes, termed Orla C3-1 and Orla C3-2, and one C4 gene, termed Orla C4, of a teleost, Japanese medaka fish (Oryzias latipes), by analyzing cDNA clones isolated from a liver library constructed using the inbred AA2 strain. The deduced basic structures of Orla C3-1, C3-2, and C4, such as the subunit chain structure, the thioester site, and the proteolytic activation site, are similar to their mammalian counterparts. However, the catalytic His residue which greatly increases the rate of thioester reaction, is replaced by Ala in Orla C3-2, implying functional differentiation between two C3 molecules. Mapping analysis revealed a close linkage between the C3-1 and C3-2 genes, indicating that they arose by a local duplication rather than by a genome-wide tetraploidization. The C4 gene belongs to a different linkage group, and no linkage was observed among the C3, C4, Bf/C2, MHC class I, and MHC class II loci. These results suggest that the MHC class III complement region was established in the tetrapod lineage, or lost in the teleost lineage.

Amino Acid Sequence↗

Altered bile composition in the gallbladder and common bile duct of patients with anomalous pancreaticobiliary ductal junction.

The high incidence of biliary tract carcinoma in patients with anomalous pancreaticobiliary ductal junction (APBDJ) has been well documented. Elevation of the secondary and free bile acid (FBA) concentrations is considered a risk factor for biliary carcinogenesis in these patients. Bile from the gallbladder and common bile duct in 12 patients with APBDJ was analyzed and compared with gallbladder bile from 19 patients with gastric cancer and a normal hepatobiliary tract. The concentrations of secondary bile acids were significantly lower in the APBDJ group than in the control group, and FBA concentrations were not detected in the gallbladder in either group. The lysolecithin (LL) in the phospholipid, which is produced from lecithin by activated phospholipase A(2) in refluxing pancreatic juice, was significantly elevated in the APBDJ group. Elevation of the LL concentration in the bile is one of the factors for the development of biliary tract carcinoma in patients with APBDJ.

Adolescent↗

Ultraviolet B radiation downregulates inducible nitric oxide synthase expression induced by interferon-gamma or tumor necrosis factor-alpha in murine keratinocyte Pam 212 cells.

Ultraviolet radiation causes inflammation characterized by erythema and swelling, but also exhibits antiinflammatory effects which have led to the use of ultraviolet B radiation (UVBR) and psoralen plus ultraviolet A (PUVA) in the treatment of psoriasis, chronic severe atopic dermatitis and uremic pruritus. In inflammatory dermatoses, a pathogenic role of nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) has been suggested. To elucidate how UVBR regulates iNOS expression in skin under inflammatory conditions, we investigated the effect of UVBR on NO production and iNOS expression in cultured murine keratinocyte Pam 212 cells stimulated with interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha). Low doses of UVBR significantly suppressed IFN-gamma- or TNF-alpha-induced NO production. UVBR also downregulated IFN-gamma- or TNF-alpha-induced iNOS expression at both the mRNA level and the protein level. These findings suggest the possibility that the down-regulatory effect of UVBR on IFN-gamma- or TNF-alpha-induced iNOS expression may, in part, explain the antiinflammatory and therapeutic properties of UVBR in inflammatory dermatoses.

Animals↗

The polymorphisms of various short tandem repeats on the Y chromosome in Japanese and German populations.

In the present study we have analyzed the genotypes at the DYS389-I, DYS389-II, DYS390, DYS391, DYS393 and DYS19 loci on the Y chromosome in Japanese and German populations. The genotypes were determined in the white blood cell DNA of 200 Japanese and 111 German males. The 8-locus haplotype combination of these six loci with our previous data on DYS388 and DYS392 revealed much lower maximum matching probability (0.0053 in Japanese and 0.0092 in Germans), much higher minimum diversity (dw(min)) (0.9947 in Japanese and 0.9908 in Germans) and more haplotypes (194 in Japanese and 110 in Germans). These very high abilities for discrimination could provide ideal tools for forensic analysis and population studies.

Discriminant Analysis↗

Differential expression of dihydropyrimidinase-related protein genes in developing and adult enteric nervous system.

Dihydropyrimidinase-related proteins (DRPs) are involved in axonal outgrowth and pathfinding. However, little is known about their significance in the enteric nervous system (ENS), the largest and most complex division of the peripheral nervous system. Using in situ hybridization (ISH) and northern blotting, we examined mRNA expression of DRP-1-4 transcripts in the developing and adult mouse digestive tract and in the adult human colon. ISH detected the mouse DRP-3 transcript in the developing ENS on embryonic day (E)12 and at the later stages as well as in the adult intestine. Mouse DRP-1 and -2 transcripts appeared at E14. DRP-2 transcript was also detected in the adult intestine although DRP-1 expression was lower in the adult. DRP-4 gene was not expressed in the ENS during development or adulthood whereas the signal was apparent in the developing and adult central nervous system (CNS). The DRP expression pattern in the human colon was similar to that of the mouse large intestine. Northern blot analysis showed that DRPs were differentially expressed in the mouse and human intestines, supporting the results of ISH. These data suggest that DRPs play a role not only in the CNS but also in the ENS.

Adult↗

Precancerous lesions of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC), also known as cholangiocellular carcinoma or peripheral bile duct carcinoma, is an intrahepatic malignant tumor that consists of cells resembling the biliary epithelium. The proportion of ICC among primary hepatic malignancies is approximately 10% worldwide. Although the etiology and pathogenesis remain unclear in a great majority of cases, preceding pathologic conditions or etiologies in the development of ICC are known or suspected in a proportion of these patients. Some forms of ICC, such as those associated with hepatolithiasis or liver fluke infestation, are endemic in parts of the world, particularly in East Asia. ICC is reportedly a late complication of primary sclerosing cholangitis. Most of these preceding pathologic conditions are forms of chronic cholangitis, and longstanding inflammation, chronic injury, and regenerative hyperplasia of the biliary epithelium may be causally related to malignant transformation. Biliary epithelial dysplasia is encountered in the intrahepatic bile ducts both near and remote from ICC foci in the liver and near and remote from the chronically inflamed biliary tree. This lesion could be a precancerous lesion, and it shows telomerase activity and increased proliferative activities. Furthermore, congenital and developmental disorders of the biliary system, such as Caroli's disease, congenital hepatic fibrosis, and pancreatico-biliary malformation are occasionally associated with ICC. Benign biliary tumors, such as biliary papillomatosis, may eventually undergo malignant transformation. These lesions could be regarded as precancerous or borderline lesions. Some ICCs may also develop in nonbiliary viral cirrhosis. In the majority of cases of ICC, however, the etiology, pathogenesis, and developmental processes and precancerous lesions of the ICC remain unclear.

Bile Duct Neoplasms↗

Clinical importance of n-3 fatty acid-rich diet and nutritional education for the maintenance of remission in Crohn's disease.

Elemental diet (ED) therapy has been established as primary therapy for Crohn's disease, and home enteral nutrition (HEN) has been reported to control relapse at a dose of more than 30kcal/kg of ideal body weight. However, a decrease in ED compliance with long-term use is becoming problem. We developed an n-3 fatty acid-rich diet and carried out nutritional education specifically for Crohn's disease patients using HEN to facilitate compliance and to improve their nutritional status. After the introduction of this n-3 rich diet, disease activity was not altered, and nutritional status, especially serum n-3 fatty acid levels, improved. The remission periods in patients with poor compliance seemed to be prolonged by the nutritional education. Thus, a n-3 rich diet in combination with nutritional education specific for Crohn's disease patients is very important for the in maintenance of high compliance and for maintaining nutritional balance.

Adolescent↗

Efficacy of oral adsorbent for treatment of peristomal fistula associated with Crohn's disease.

Perianal fistulae are frequently seen complications in Crohn's disease. Although surgical procedures such as Seton's method have been devised, many patients still suffer from fistulae that are resistant to conventional therapy. We administered oral adsorbent to a patient with disease Crohn's who had a complicated peristomal fistula that did not improve with conventional therapy. Six grams of oral adsorbent (AST-120) were added daily to a regimen of elemental diet therapy and prednisolone. The fistula gradually decreased in size after the administration of the oral adsorbent, and had healed completely after 40 days' treatment. There were no side effects from the oral adsorbent. This case report suggests that oral adsorbent is an effective treatment for peristomal fistula associated with Crohn's disease.

Administration, Oral↗

Preventive efficacy of butyrate enemas and oral administration of Clostridium butyricum M588 in dextran sodium sulfate-induced colitis in rats.

Butyrate enemas have been reported to be effective in ulcerative colitis. However, long-term use is difficult because of the troublesome procedure and the unpleasant smell. We therefore investigated the effects of the oral administration of Clostridium butyricum M588 (CBM588), an enterobacterium producing butyrate, in dextran sodium sulfate (DSS)-induced colitis in rats. First, we confirmed the effects of pre-treatment with a butyrate enema on DSS colitis. We then studied the efficacy of oral administration of CBM588 which was started 1 week prior to the induction of DSS colitis. In the CBM588 group, the ulcer index and myeloperoxidase (MPO) activity in the distal colon were significantly lower than in the control group. Proliferating cell nuclear antigen (PCNA) immuno-positive cells were increased around the ulcer in the CBM588 group. In regard to the contents of the cecum and colon, the proportions of Lactobacillus and Eubacterium were increased in the cecum in the CBM588 group. Further, there were significant increases of n-butyrate, propionate, and acetate concentrations in the cecum in the CBM588 group. These results indicated that the oral administration of CBM588 alleviated DSS-induced colitis, and may be useful instead of butyrate enema.

Acetates↗

Bone mineral density and osteo sono assessment index in adolescents.

The standard value for bone mineral density in the distal radius (R-BMD) and the osteo sono assessment index (OSI) in the os calcaneus for each sex and age in teenagers have not yet been fully reported. The R-BMD and OSI of junior and senior high school students were measured by dual energy X-ray absorptiometry (DEXA) or by a quantitative ultrasound technique. Subjects measured by DEXA included 635 junior and senior high school students (274 males and 361 females, aged 12-17 years). Ultrasound measurements were made for 2878 subjects (1733 males, 1145 females, aged 12-18 years). All subjects filled out questionnaires about their past history, family history, past and present eating habits, sports activities, and for females, the presence of menses, regularity of menses, and so on. The R-BMD in 15- to 17-year-old males was significantly higher than that in females. The R-BMD rate of increase in males was almost linear; the rate of increase in females was significantly highest from ages 12 to 13, after which R-BMD increased gradually. The OSI in 15- to 18-year-old males was significantly higher than that in females. The OSI rate of increase in males was almost linear from ages 12 to 17. The OSI in females, except in 14-year-olds, was roughly equal at each age. The OSI was significantly higher in those who regularly participated in sports, either currently or in the past. It was significantly higher in those who previously or currently consumed milk on a daily basis compared with those who had consumed little or no milk. To prevent osteoporosis, increasing peak bone mass is very important. Adequate calcium intake from dairy products which are rich in calcium and absorbed easily, and exercise in adolescence, are expected to result in increased bone formation and increased OSI.

Absorptiometry, Photon↗

Limitations of urinary telomerase activity measurement in urothelial cancer.

The reported frequency of detectable telomerase activity in spontaneously voided urine samples from patients with urothelial cancer varied from 0 to 85%. We examined stasis in the bladder and specimen storage as interfering conditions in this assay. Telomerase activity in exfoliated cells was measured by a polymerase-chain-reaction-based assay in spontaneously voided urine from urothelial cancer patients. Effects of retention in the bladder and specimen storage from voiding to measurement of telomerase activity were modeled by suspending 10(6) cells from the cancer-derived T24 line in normal urine (pH 6.5) at 37 degrees C and 25 degrees C, respectively. Hematuria was modeled by adding hemoglobin. In T24 cells suspended in urine at 37 degrees C, telomerase activity had decreased to approximately 20% of preincubation activity after 1 h, and had disappeared after 3 h. In urine at 25 degrees C, telomerase activity in T24 cells had decreased to approximately 40% of preincubation activity at 1 h and to <10% at 6 h. When we examined telomerase activity in exfoliated cells in spontaneously voided urine from urothelial cancer patients (excluding first-voided morning specimens), telomerase activity was detected in only 21% of samples (four of 19) despite measurement with 1 h of voiding and steps to avoid hemoglobin interference. Measurement of telomerase activity in spontaneously voided urine is insufficiently sensitive and reliable for the diagnosis of urothelial cancer.

Carcinoma, Transitional Cell↗

Local mechanical properties measured by atomic force microscopy for cultured bovine endothelial cells exposed to shear stress.

Morphology and mechanical properties of cultured endothelial cells were measured, using a novel atomic force microscope (AFM) system, developed in our laboratory, in conjunction with an inverted confocal laser scanning microscope. We used this system to examine endothelial cell both in static cultures and exposed to a shear stress of 2 Pa. Initially, the three-dimensional topography of a cell was measured by the AFM and a location was selected for the subsequent measurement of the mechanical response of the cell. The surface of statically cultured cell was smooth. The cell height was not altered by the exposed duration of shear stress. A relationship between external force, F, and the indentation depth, delta, was obtained for several different locations on a cell. This force-indentation response was modelled using a quadratic equation, F = adelta2 + bdelta, indicating that two parameters, a and b, will be constants which are representative of the mechanical response. Endothelial cells cultured at static conditions demonstrated a polygonal shape and less stiff mechanical characteristics around the nucleus compared to those at peripheral regions. The stiffness of the endothelial cells exposed to shear stress increased with the duration time of exposure. At 6-h exposures, the stiffness was higher at upstream side of the cell than the downstream side. However, after 24-h exposure, the stiffness was similar on both sides of the cell. These changes in the stiffness of endothelial cells when exposed to shear stress were suggested to correspond with the distribution of stress fibers in the cell.

Animals↗

Disturbances of spatial vision and object vision correlate differently with regional cerebral glucose metabolism in Alzheimer's disease.

There is evidence of two neuronal systems for visual cognition which are referred to as spatial vision and object vision. We subjected 49 patients with mild-to-moderate probable Alzheimer's disease (AD) to tasks associated with these two types of visual cognition. Visual counting was employed as a task to assess visuospatial recognition. Identification of overlapping figures and discrimination of visual forms were used as visuoperceptual tasks that require an ability to recognize objects. Regional cerebral glucose metabolism (rCMRglc) of the subjects was also determined by positron emission tomography. Multivariate statistics controlling for the confounding factors assessed the correlation between the task performances and the rCMRglc. The visual counting score significantly correlated with the metabolic rate of the bilateral inferior parietal lobules. On the other hand, the scores of the visuoperceptual tasks significantly correlated with the metabolic rate of the right middle temporal gyrus and the right inferior parietal lobule. The present study showed that visuospatial disturbance was related to bilateral parietal metabolism, and that visuoperceptual disturbance was related to right temporo-parietal metabolism in patients with mild-to-moderate AD.

Aged↗

Characterization of mice antisera elicited with a ciguatoxin tetracyclic synthetic ring fragment (JKLM) conjugated to carrier proteins.

As a good alternative to the lack of pure ciguatoxin (CTX), conjugates of JKLM ring fragment, a carboxylic derivative of the right-hand tetracyclic terminus portion of CTX-1B (the most potent CTX) with two carrier proteins have been synthesized. Two procedures using different amount of hapten were evaluated: (i) a bulk technique (3-5 mg) via the N-hydroxysuccinimide ester of the carboxylic fragment in the presence of a water-soluble carbodiimide according to the standard method in aqueous buffer, or (ii) a micro-scale technique (300 microg) via the mixed anhydride method performed in a reversed micellar medium. In both cases, bovine serum albumin and ovalbumin were respectively used for immunization of BALB/c mice and antibody screening by a solid phase enzyme-linked immunosorbent assay (ELISA). Using the conjugates obtained through the micro-scale procedure, a long-term immunization schedule appeared to be more efficient to specifically trigger the mice immune system. These antisera titers determined in an end-point titration standard ELISA format were found around 1/128,000 as compared to 1/16,000 obtained in the short-term protocol (immunogen prepared via the bulk procedure). In competitive inhibition ELISA experiments, both types of antisera did not significantly cross-react with a brevetoxin congener (PbTx-3), okadaic acid (OA), monensin or other polyether compounds, but only sera from the short-term protocol did show high cross-reactivity to CTX-1B (133%). With sera from the long-term protocol, a lower detection limit for JKLM (1.23 x 10(-9) M) was achieved by implementation of a biotin-avidin amplification system rather than by miniaturization of the assay in Terasaki plates. This study confirms the feasibility of the immunological approach for CTXs assay in fish tissues, but also emphasizes the importance of (i) the choice of the hapten to construct a relevant well-defined immunogen, (ii) the immunization schedule to obtain hapten-specific Abs still exhibiting high cross-reactivity to CTXs.

Animals↗