A biopsy-negative esophageal cancer: diagnosis by combination of bite biopsy and endoscopic mucosal resection using a cap-fitted panendoscope (EMRC).
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Publications and source records attributed to N Nakamura.
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BACKGROUND AND STUDY AIMS: Endoscopic variceal ligation (EVL) is an alternative to sclerotherapy for the treatment of esophageal varices, but is associated with higher rates of recurrence and subsequent bleeding than sclerotherapy. To prevent recurrence of varices after EVL, we have developed a low-dose diode laser therapy combined with the injection of indocyanine green, which allows enhanced tissue absorption of the laser beam selectively around varices. In this study we investigated the efficacy and safety of this technique. PATIENTS AND METHODS: Eight patients with F2 or F3 esophageal varices were enrolled. At 1 week after EVL, indocyanine green solution (1 mg/ml) was injected submucosally around the remaining varices. A diode laser (power 10 watts) was applied to the surface from the esophagogastric junction to 5 cm above it. The spot size was kept to 5 mm in diameter. RESULTS: Laser irradiation was performed safely, without bleeding from the varices, or perforation. There were no major complications. Endoscopy 1 month later showed F0 forms in seven patients, F1 in one patient, and no red color sign in any patient. No recurrence of varices has been observed in any of the patients during the follow-up period of at least 12 months. CONCLUSION: This technique may provide a simple, safe and effective procedure, as an additional treatment to EVL, for the prevention of recurrence of esophageal varices.
Further studies on leaves of Annona montana led to isolation of one iso-acetogenin, montanacin G, three pairs of acetogenins, montanacin H-J and 34-epi-montanacin H-J, together with four known acetogenins, gigantetrocins A and B, annonacin and cis-annonacin. Montanacin G belongs to the iso-acetogenin group with a terminal 2,4-trans-ketolactone unit. Montanacin H-J and 34-epi-montanacin H-J contain the rare gamma-hydroxy-gamma-methyl-gamma-lactone moiety. The cytotoxic activities of these compounds, together with previously reported acetogenins, montanacins B and C, were examined against Meth-A and LLC tumor cell lines in vitro.
OBJECTIVE: Growth characteristics of ameloblastomas involving the inferior alveolar nerve were examined to determine the most appropriate surgical management of the nerve at the time of the surgical procedure. STUDY DESIGN: Clinical and histopathologic examinations were performed on 22 resected mandibles in which the inferior alveolar nerve was lying adjacent to, or contained within, the tumor. RESULTS: Patterns of tumor involvement of the nerve bundle were evaluated with respect to the presence of bone (11 patients) or connective tissue wall (7 patients) between the tumor and the nerve bundle, and tumor infiltration of perineural connective tissue (4 patients). Neither invasion into the nerve sheath nor invasion into the nerve itself by the ameloblastoma was detected. Tumor infiltration of the tissue surrounding the nerve was identified for the multicystic and solid types but not for the unicystic type. Presence of bone or connective tissue wall between the tumor and the nerve bundle was dominant in the unicystic and plexiform ameloblastomas, whereas tumor infiltration of the perineural tissue was frequently observed in ameloblastomas with the follicular pattern. CONCLUSION: The preservation of the inferior alveolar nerve may be possible in the management of the unicystic type of ameloblastoma. However, a more radical approach is necessary for treatment of multicystic or solid tumors, especially those exhibiting a follicular pattern.
A case of thymic carcinosarcoma in an 83-year-old Japanese man is presented. He died of superior vena cava syndrome caused by a rapidly enlarged anterior mediastinum tumor eight months after initial symptoms. Autopsy revealed a 16 x 12 x 25 cm-sized, tan yellow, whitish tumor with a multinodular and microcystic appearance located in the left anterior mediastinum, which involved the residual thymus. The tumor had directly invaded the left pleura, and had metastasized to the right lung and spleen. Histologic examinations of the primary tumor showed a sarcomatous component consisting of racquet- or spindle-shaped cells with cross striations, and small nests of atypical squamous cells scattered throughout the tumor; neither transition between the two components nor intermediate cells with both epithelial and mesenchymal features was seen. Electron microscopic and immunohistochemical examinations confirmed the rhabdomyomatous differentiation of the sarcomatoid component. To our knowledge, there have been only two reported cases showing histologic features similar to the present tumor. For the histogenesis of thymic carcinosarcoma, we propose two hypotheses. The first is that sarcomatous cells are derived from carcinomatous cells by tumoral metaplasia. Secondly, that this type of tumor originates from thymic primitive cells with multidirectional differentiation potential. In accordance with the latter, we consider that the present tumor originated from thymic primitive cells. Thymic carcinosarcoma is a highly malignant tumor, and most patients die within a year. Appropriate therapies must be developed.
PURPOSE: To evaluate the relative abilities of the solid Giemsa staining (conventional) and fluorescence in situ hybridization (FISH) methods in the detection of stable chromosome aberrations in the peripheral blood lymphocytes of A-bomb survivors. MATERIALS AND METHODS: Lymphocytes from a total of 230 A-bomb survivors for whom prior chromosome aberration data had been obtained by the conventional method were recently examined afresh using FISH in which chromosomes 1, 2 and 4 were painted with composite probes. RESULTS: It was found that the early use of the solid Giemsa staining method had allowed the detection of translocations with a mean frequency of 73% of the value for the genome-equivalent translocation frequency (F(G)) that was now obtained using FISH. The disparity may at least in part be due to the reciprocal exchange of seemingly identical amount of chromosome material; such exchanges can escape detection by the conventional method but can be readily identified using FISH. CONCLUSION: It has previously been established that the conventional method can detect about 20% of radiation-induced translocations as abnormal monocentric chromosomes. Present results indicate that an additional 50% can be detected if proper karyotyping is conducted and the remaining 30% are not likely to be detected unless FISH or banding methods are used. Thus, solid Giemsa staining accompanied by karyotyping may not be quite as unsuitable as is generally assumed for retrospective biodosimetry analyses, which deal mainly with stable aberrations.
PURPOSE: To estimate the translocation-induction rate under chronic exposure conditions by measuring chromosome aberration frequencies in lymphocytes from Mayak nuclear workers using fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: Lymphocytes were examined from 27 nuclear workers at the Mayak Production Association and two control individuals using FISH with probes for chromosomes 1, 2 and 4. Official doses derived from worker film-badge records varied from 0 to 8.50 Gy. RESULTS: The mean (+/-SD) genome-equivalent translocation frequency (F(G)) was 2.30 (+/-0.75)% in the zero-dose group (n = 7), and Poisson regression analysis provided the best-fit equation of F(G)(%) = 2.96(+/-0.39) + 0.69(+/-0.14)D + 0.12(+/-0.05)A, where D is the film-badge-derived dose (Gy), and A is age centred at 67 years. The induction rate would increase to nearly 1% Gy(-1) if the radiation dose to bone marrow, one of the major organs for lymphocytes and where their precursor cells reside, is considered. CONCLUSION: The estimated induction rate in vivo appeared substantially smaller than linear coefficients estimated from various in vitro studies.
Oxidative stress may be an important factor in the development of diabetic complications. Advanced glycation end-products have drown attention as potential sources of oxidative stress in diabetes. We investigated the protective effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on oxidative DNA damage from reactive oxygen species or advanced glycation end-products in vitro, as well as effects of main fluvastatin metabolites and other inhibitors of the same enzyme, pravastatin and simvastatin. Protective effects were assessed in terms of the DNA breakage rate in a single-stranded phage DNA system in vitro. DNA was exposed to either reactive oxygen species or advanced glycation end-products. Fluvastatin and its metabolites showed a strong protective effect comparable to those seen with thiourea and mannitol, though pravastatin and simvastatin did not exert clear protective effects. Furthermore, fluvastatin reduced the mutagenesis by reactive oxygen species or advanced glycation end-products in Salmonella typhimurium test strains. Both pravastatin and simvastatin still lacked protective activity. Fluvastatin and its metabolites protect against oxidative DNA damage and may reduce risk of consequent diabetic complications.
We investigated the effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on reactive oxygen species (ROS) and on oxidative DNA damage in vitro, as well as the effects of the main fluvastatin metabolites (M2, M3, and M4) and other inhibitors of the same enzyme, pravastatin and simvastatin. The hydroxyl radical and the superoxide anion scavenging activities of fluvastatin and its metabolites were evaluated using an electron spin resonance spectrometer. Fluvastatin and its metabolites showed superoxide anion scavenging activity in the hypoxanthine-xanthine oxidase system and a strong scavenging effect on the hydroxyl radical produced from Fenton's reaction. Protective effects of fluvastatin on ROS-induced DNA damage of CHL/IU cells were assessed using the single-cell gel electrophoresis assay. CHL/IU cells were exposed to either hydrogen peroxide or t-butylhydroperoxide. Fluvastatin and its metabolites showed protective effects on DNA damage as potent as the reference antioxidants, ascorbic acid, trolox, and probucol, though pravastatin and simvastatin did not exert clear protective effects. These observations suggest that fluvastatin and its metabolites may have radical scavenging activity and the potential to protect cells against oxidative DNA damage. Furthermore, ROS are thought to play a major role in the etiology of a wide variety of diseases such as cellular aging, inflammation, diabetes, and cancer development, so fluvastatin might reduce these risks.
Endometriosis, adenomyosis and leiomyomata develop in women of reproductive age and regress after menopause or ovariectomy, suggesting that they grow in an oestrogen-dependent fashion. We investigated whether polymorphism in the oestrogen receptor-alpha (ERalpha) gene is related to oestrogen-dependent benign uterine disease. A total of 203 women with regular menstrual cycles underwent laparotomy or laparoscopy and were diagnosed histologically with endometriosis, adenomyosis and/or leiomyomata. Patients with cervical carcinoma in situ, tubal occlusion or adhesion but no other gynaecological disease were considered to be disease-free. A total of 179 women undergoing annual health examination were grouped as reference population. The distribution of PVUII genotypes (PP, Pp, and pp) of the ERalpha gene was different between each pair of the four groups of endometriosis, adenomyosis/leiomyomata, disease-free, and reference population (P = 0.022-0.0005), except between the former two groups. The PP genotype was less frequent in the groups of endometriosis (P = 0.0002) and adenomyosis/leiomyomata (P = 0.002) as compared to that in the disease-free group. In the endometriosis group, there was no difference in the distribution of PVUII genotypes due to complicating diseases (adenomyosis and/or leiomyomata) or severity of the clinical stages. These results suggest that the PVUII polymorphism of the ERalpha gene is associated with the risk for endometriosis, adenomyosis, and leiomyomata.
Anti-atherosclerotic effects of human macrophage colony-stimulating factor were investigated using rabbits fed a high cholesterol diet. Rabbits fed a diet containing 2% cholesterol for 59 days developed hyperlipidemia and atheromatous aortic plaques. They were then administered 80 microg/kg/day of either macrophage colony-stimulating factor or human serum albumin, as a control, for the next 12 weeks. Compared with the control group, rabbits treated with macrophage colony-stimulating factor had significantly fewer plaques on the inner surface of the thoracic and abdominal aortae, and half the sectional area of thickened intima in the aortic arch, as well as in the thoracic and abdominal aortae. Macrophage colony-stimulating factor also decreased the cholesterol content of the atherosclerotic lesions. Serobiochemical analyses revealed that macrophage colony-stimulating factor increased the levels of high density lipoprotein-cholesterol significantly, without influencing other lipid parameters such as the level of low density lipoproteins. The effects of macrophage colony-stimulating factor were evident until the fourth week of drug injection, at which time anti-human macrophage colony-stimulating factor antibodies were clearly induced in the serum. These results indicate that exogenously administered macrophage colony-stimulating factor suppresses atherosclerotic lesions induced by a high cholesterol diet by activating lipid metabolism in vivo.
The efficacy of two different cationic liposomes, Lipofectin and hemagglutinating virus of Japan (HVJ)-cationic liposomes, on nuclear uptake of fluorescence-labeled phosphorothioate oligodeoxyribonucleotide (S-ODN) by ligament scar fibroblasts and suppression of decorin mRNA expression when antisense decorin S-ODN was transferred was investigated. There was no significant difference in nuclear uptake of fluorescent ODN between the two methods. However, only HVJ-cationic liposomes had a significant effect on suppression of decorin mRNA expression levels. To address the discrepancy, the molecular integrity of the transferred ODN in the cells was assessed by analysis of fluorescence resonance energy transfer (FRET) within double-fluorescence-labeled S-ODN. More than 70% of the ODN transfected by HVJ-cationic liposomes remained intact within the nucleus at 20 h after transfection, while the majority of the ODN transferred by Lipofectin was degraded at this point. These results suggest a strong relationship between the nuclear integrity of transfected antisense ODN and its suppression of target mRNA expression.
We surveyed proteins capable of binding to the cytoplasmic domain of Na(+)/H(+) exchanger (NHE)1 in a rat brain cDNA library with the yeast two-hybrid system. One clone obtained coded for a protein reported previously as a human calcineurin homologous protein (CHP). Since CHP is homologous to the regulatory subunit B of calcineurin, we expected a possible interacting partner of CHP like the catalytic subunit of calcineurin (calcineurin A), and surveyed this putative partner again with the yeast two-hybrid system. A clone thus obtained coded for a kinase, which is basically the same as that reported for human DRAK2. Overexpression of the rat homologue of DRAK2 caused apoptosis-like cell death of NIH3T3 cells, which was dependent on the kinase activity, confirming the previous result for DRAK2. The purified CHP and rat DRAK2 proteins synthesized in Escherichia coli could bind in vitro. CHP and rat DRAK2 expressed in COS-7 cells were found to be localized in the Golgi apparatus and nucleus, respectively. Some of them was also found in the membrane peripheral region. When they were co-expressed in the same cells, most of CHP moved to the nucleus where rat DRAK2 is located, suggesting in vivo interaction of these proteins. However, minor but significant fractions of both proteins were also found in the membrane peripheral region. Rat DRAK2 is expressed highly in thymus, spleen, and testis, where the apoptosis plays an important role in physiology.
Sorting nexin 1 (SNX1) is a protein that binds to the cytoplasmic domain of plasma membrane receptors. We found that mouse sorting nexin 1 (SNX1) (521 amino acid residues) could partially rescue a yeast vam3 mutant defective in docking/fusion of vacuolar membranes. In mammalian cells, SNX1 is peripherally associated with membrane structures and localized immunochemically with EEA1, a marker protein of early endosomes. These results suggest that SNX1 regulates endocytic trafficking of plasma membrane proteins in early endosomes. Gel filtration of cell lysates and the purified recombinant protein, together with two-hybrid analysis, indicated that SNX1 self-assembles into a complex of approximately 300 kDa.
We investigated the effects of Orengedoku-to (Huanglian-Jie-Du-Tang in Chinese) and Senkanmeimoku-to (Xygan-Ming-Mu-Tang in Chinese), traditional herbal medicines, on experimantal elevation of aqueous flare in pigmented rabbits. To produce the elevation of aqueous flare in rabbits, prostaglandin E2 (PGE2) was applied to the cornea with use of a glass cylinder, or lipopolysaccharides (LPS) were injected into the ear vein. Animals were pretreated by the oral administration of 150 g/day of food containing 0.7%, 0.2% or 0.07% (w/w) Orengedoku-to, or 2%, 0.6% or 0.2% (w/w) Senkanmeimoku-to for 5 days. Aqueous flare was measured with a laser flare-cell meter. Pretreatment with 0.7% or 0.2% Orengedoku-to and 2% Senkanmeimoku-to did suppress significantly (P < 0.05) elevation of aqueous flare induced by PGE2. Pretreatment with 0.7% or 0.2% Orengedoku-to and 2% or 0.6% Senkanmeimoku-to significantly suppressed (P < 0.001) elevation of aqueous flare induced by LPS. It is possible that Orengedoku-to and Senkanmeimoku-to may migrate some forms of uveitis.
The progression of renal damage resulting from reduced nephron mass has been extensively studied in the 5/6 nephrectomized rat. However, reabsorption of small peptides and D-glucose across the renal proximal tubule in this model remains poorly understood. In this study, we examined the alterations of H(+)-peptide cotransporters (PEPT1 and PEPT2) and Na(+)-D-glucose cotransporters (SGLT1 and SGLT2) in chronic renal failure. Two weeks after surgery, H(+)-dependent [(14)C]glycylsarcosine uptake by the renal brush-border membrane vesicles isolated from 5/6 nephrectomized rats was significantly increased compared with that from sham-operated controls. Kinetic analysis revealed that the maximum velocity value for [(14)C]glycylsarcosine uptake by the high-affinity-type of peptide transporter was increased threefold by 5/6 nephrectomy, without significant changes in the apparent Michaelis-Menten constant value. Competitive PCR analyses indicated that the expression of PEPT2 mRNA was markedly increased in the remnant kidney, but PEPT1, SGLT1, and SGLT2 mRNA levels showed no significant changes. These findings indicated that the high-affinity-type H(+)-peptide cotransport activity is upregulated by 5/6 nephrectomy, accompanied by the increased expression of PEPT2. The upregulation of PEPT2 expression would result in an increase in reabsorption of small peptides and peptide-like drugs across the brush-border membranes in chronic renal failure.
A Ni/SiO2 catalyst was prepared by homogeneous precipitation of nickel hydroxide in a sol-gel-derived wet silica gel. The preparation process consists of two successive steps: gelation of silica in the presence of nickel nitrate and urea at 50 degrees C, followed by aging at higher temperature, typically at 80 degrees C, to decompose the urea. The decomposition of urea increases the pH of the solution in the wet gel, leading to the concurrence of structural rearrangement of silica gel and deposition of nickel species. As a result, the structure of the silica changes from a ramified polymeric network into particle aggregates that entrap the nickel cations in the particles. The resulting Ni/SiO2 contains large mesopores that have high thermal stability up to 1000 degrees C and highly dispersed Ni metal particles with typical crystallite size of 4 nm even at high Ni content at 20 wt%.
To examine the intracellular localization of neutral sphingomyelinase 1 (nSMase 1), a rabbit polyclonal antibody was raised against a recombinant form of the enzyme expressed in E. coli. It has been reported that, in rat liver or in ascites hepatoma AH7974, high activity of neutral sphingomyelinase (SMase) is found at the plasma membrane, with a lesser but significant amount in nucleus and cytoplasm. The biochemical properties, dithiothreitol requirement and high salt concentration dependency, of cloned and expressed nSMase 1 resemble those of previously described nuclear neutral SMase of AH7974. The present study was therefore focused on the nuclear localization of this enzyme. Western blotting of subcellular fractions using anti-rat nSMase 1 antibody revealed most nSMase 1 to be associated with the nuclei and some with microsomes, but not with plasma membranes. Consistently, neutral SMase activity in nuclear extract was immunoprecipitated by the antibody, while that of plasma membranes was not. The results indicate that nSMase 1 mainly resides in the nucleus and may thus differ from neutral SMase in plasma membrane. On gel-filtration column chromatography of nuclear extract, the profile of neutral SMase activity corresponded well with immunoreactive protein bands on western blotting, suggesting that a large part of nuclear neutral SMase may be nSMase 1. Removal of the nuclear envelope by treatment with Triton X-100 did not significantly decrease the amount of nuclear nSMase 1, and western blotting of subnuclear fractions (i.e. nuclear envelope, chromatin, and nuclear matrix) revealed nSMase 1 signal exclusively in the nuclear matrix. Immunocytochemistry with AH7974, as well as rat fibroblast cell line 3Y1, demonstrated nSMase 1 to be localized mainly in the nucleus, with some in the cytoplasm. Moreover, immuno-electron microscopy clearly showed the signal of nSMase 1 to be more dense in the nucleus than in the cytoplasm of AH7974.