[Desmoplastic infantile ganglioglioma (DIG)].
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Biomedical subjects
Publications and source records attributed to M Mizuno.
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BACKGROUND: Depressed neoplastic lesions of the colorectum have been specified in patients with familial adenomatous polyposis (FAP). The aim of this study was to characterize endoscopic, histologic, and immunohistochemical features of depressed adenoma of the duodenum in patients with FAP. METHODS: Duodenoscopy was performed on 25 patients with FAP, and the neoplastic nonampullary lesions were classified as polypoid or depressed adenomas. The grade of dysplasia, the proliferative activity determined by Ki-67 labeling index (LI), and the grade of p53 expression were compared between polypoid and depressed neoplasia. RESULTS: Ten subjects had depressed nonampullary adenoma, whereas polypoid adenoma was found in the remaining 15 subjects. Moderate dysplasia was more frequent in depressed adenoma than in polypoid adenoma (70% vs. 27%, P = 0.04). Whereas p53 expression was not different between the two adenoma groups, the LI was significantly higher in depressed adenoma than in polypoid adenoma (59.7 +/- 9.5 vs. 47.5 +/- 10.7, P < 0.01). CONCLUSIONS: Depressed adenoma of the duodenum is a distinctive phenotype of duodenal neoplasm in patients with FAP. The high proliferative activity of depressed adenoma suggests that there may be a need to survey FAP patients with such lesions intensively.
Tumor necrosis factor (TNF)-alpha has been shown to exert cytotoxic or cytostatic effects on tumor cells, but susceptibility to TNF-alpha varies among different types of cells. TNF-alpha activates a transcription factor, nuclear factor-kappaB (NF-kappaB), which induces a wide variety of genes and causes pleiotrophic responses. In this study, the relationship between susceptibility to TNF-alpha and activation of NF-kappaB was investigated in six human malignant glioma cell lines. Cell proliferation analysis revealed that only one cell line, SK-MG-1, was sensitive to TNF-alpha and that the other five, including U-251MG, were resistant. Electrophoretic mobility-shift assay showed that TNF-alpha strongly activated a subtype of NF-kappaB, the p50-p65 heterodimer, in all of the resistant cell lines tested. However, this activation was weak in the sensitive cell line, SK-MG-1. Activation of NF-kappaB by TNF-alpha in the resistant cell lines resulted in a significant increase of a reporter gene expression driven by NF-kappaB site, suggesting a possibility that activation of p50-p65 confers resistance to TNF-alpha. To test this hypothesis, we established a stable cell line that expresses an inducible dominant negative NF-kappaB (p65 DN) protein in one of the TNF-alpha-resistant cell lines, U-251MG. In the established clone, induction of p65 DN protein decreased TNF-alpha-dependent increase in the DNA binding of p50-p65 heterodimer and NF-kappaB-dependent reporter gene activity. Although no growth inhibition of this clone was observed by TNF-alpha treatment, induction of p65 DN together with TNF-alpha resulted in a significant decrease in cell number. Cell cycle analysis revealed that this growth inhibition was due to the impairment of cell cycle progression. These results indicate that an active NF-kappaB complex, such as the p50-p65 heterodimer, plays a crucial role in the progression of cell cycle in malignant glioma cells. Refractoriness to TNF-alpha treatment could be prevented by inhibiting NF-kappaB activation.
In the present study, the synergistic effect of mild hyperthermia in combination with gene expression of interferon-beta (IFN-beta) was examined in vitro in the human glioma cell line U87MG. The cells transiently expressed the IFN-beta gene under the control of the mouse mammary tumor virus promoter and were then subjected to temperature elevation (41 degrees C for 1 h). In terms of the cell killing effect, the optimum scheme was obtained by transfection for 4 days before hyperthermia, i.e. rate in the time course of IFN-beta gene expression. The relative specific growth rate decreased to 32% compared with the control while it was only 40% under the hyperthermic conditions. These observations suggest that IFNbeta expression was able to enhance the sensitivity of transfected glioma cells to mild hyperthermia.
Rats pretreated with traces of LPS developed acute fatal shock syndrome after i.v. administration of a mAb that inhibits the function of a membrane complement regulatory molecule. Such a shock was not observed after the administration of large amounts of LPS instead of the mAb following LPS pretreatment. The lethal response did not occur in rats depleted of either leukocytes or complement, and a C5a receptor antagonist was found to inhibit the reaction. Furthermore, LPS-treated rats did not suffer fatal shock following the injection of cobra venom factor, which activates complement in the fluid phase so extensively as to exhaust complement capacity. Therefore, complement activation on cell membranes is a requirement for this type of acute reaction.
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In order to clarify the utility of the vestibular evoked myogenic potential (VEMP) in detecting acoustic tumors, we report two patients who were found to have normal auditory brainstem responses (ABRs) and abnormal VEMPs. To record VEMPs, electromyographic responses to brief loud clicks (0.1 ms at 95 dBnHL) were amplified and averaged on the sternocleidomastoid muscle ipsilateral to the stimulated side. The stimulation rate was 5 Hz and the analysis time 50 ms. The first case was a 54-year-old woman in whom VEMPs were absent on the affected side while caloric tests and ABRs were normal. The second case was a 58-year-old woman whose VEMPs were absent on the affected side while caloric tests revealed a 22% canal paresis and normal ABRs. These results and previous studies suggested that the VEMP could reflect a function different from those evaluated by the ABR or the caloric test. We concluded that the VEMP can provide useful information in diagnosing acoustic tumors.
BACKGROUND & AIMS: Several studies have indicated that host factors are important in Helicobacter pylori-induced gastroduodenal diseases. We examined the pathological role of host immune responses in H. pylori infection by reconstituting components of the human immune system into severe combined immunodeficient (SCID) mice by transplantation of peripheral blood mononuclear cells (PBMCs) from H. pylori-infected patients. METHODS: PBMCs obtained from patients with mucosa-associated lymphoid tissue (MALT) lymphoma were injected intraperitoneally into SCID mice, designated MALToma-hu-SCID mice. One month after transplantation, H. pylori was administered orally to the mice. The mice were killed and examined for pathological changes and immunologic features. RESULTS: Human lymphocytes were detected in hu-SCID mice, and T- and B-cell functions were preserved for 1 month. Administration of H. pylori led to gastric ulcers with bleeding in the MALToma-hu-SCID mice. The gastric mucosa of control mice injected with Escherichia coli or transplanted with PBMCs from patients with peptic ulcers or gastritis or from healthy volunteers showed no pathological changes. CONCLUSIONS: Host immune responses against H. pylori appear to be involved in the development of gastric ulcers in patients who have MALT lymphoma.
BACKGROUND: Serrated adenoma is a recently recognized epithelial neoplasm of the colorectum. The aim of this study is to clarify the colonoscopic features of serrated adenomas. METHODS: The endoscopic findings for 52 serrated adenomas of the colorectum were investigated; these were then divided into three groups according to surface features. The histologic type (tubular, tubulovillous or villous) and the incidence of high-grade dysplasia were compared among the three groups. RESULTS: The surface under chromoscopy showed a hyperplastic pattern in 17 lesions, a cerebriform pattern in 18 lesions and a combined pattern in 17 lesions. The tubular type of serrated adenoma was predominant in the hyperplastic pattern group (94%), whereas the tubulovillous or villous histologic types were frequent in the cerebriform pattern (89%) and combined pattern (82%) groups. High-grade dysplasia was found in 18% of the combined pattern adenomas; the incidence was lower in hyperplastic (6%) or cerebriform pattern (0%) adenomas. CONCLUSIONS: Surface features of serrated adenomas have a close correlation with their histologic type. A combined hyperplastic-cerebriform surface pattern under chromoscopy was seen only in serrated adenomas.
The relationships between skeletal muscle morphology, particularly muscle fiber capillary density, and serum lipid profiles were evaluated in 25 non-obese men aged 18 to 36 years (body mass index [BMI], 22.7 +/- 2.5 kg/m2; body fat, 13.6% +/- 4.0%, maximal oxygen uptake [VO2max], 46.2 < or = 6.3 mL/kg/min). Skeletal muscle samples were taken from the vastus lateralis using the needle-biopsy method. The fiber types (I, IIa, and IIx) and their percent distribution, the indices of capillary density, and the diffusion index expressed as the cross-sectional area occupied by one capillary were determined. Blood samples were drawn from the antecubital vein after a 12-hour fast. Based on Pearson's correlation analysis, the number of capillaries around type IIx fiber correlated inversely with the serum level of low-density lipoprotein cholesterol ([LDL-C] r = -.50, P < .05). The number of capillaries per fiber (cap/fiber ratio), number of capillaries per area (cap/mm2), and capillaries around each fiber type correlated inversely with the serum level of apolipoprotein B ([apo B] r = -.40 to -.54, P < .05 to .01). Further, the diffusion index for each fiber type correlated positively with LDL-C and apo B (r = .42 to .50, P < .05 to .01). Among 14 subjects in whom high-density lipoprotein cholesterol (HDL-C) subfractions were analyzed, a positive correlation was found between cap/mm2 and HDL2-C (r = .64, P < .05). Partial correlation analysis showed that these correlations either remain or improve after adjusting for age, VO2max, and body fatness. These results indicate that skeletal muscle capillary density and diffusion capacity are related to lipid and apolipoprotein concentrations for both type I and type II fibers.
Fluorescence-labeled glycoconjugate polymers carrying carbohydrate segments of a globotriaosyl ceramide (Gb3) were synthesized and subjected to biological assays using Escherichia coli O-157 strains and Shiga-like toxins (Stx-I and Stx-II). For the fluorescence labeling, a new polymerizable fluorescent monomer with a TBMB carbonyl chromophore (Ex. 325 nm, Em. 410 nm) was designed. A glycosyl monomer of the trisaccharide segment of Gb3 was prepared from p-nitrophenyl beta-lactoside and copolymerized with acrylamide and the fluorescent monomer to prepare a fluorescence-labeled glycoconjugate copolymer carrying [alpha-D-galactopyranosyl-(1-->4)-beta-D-galactopyranosyl]-(1-->4)-beta- D-glucopyranoside. The polymer showed potent neutralization activity against Stx-I and also binding activity onto E. coli O-157 strains.
Chemo-enzymatic addition of a high-mannose type oligosaccharide to eel calcitonin (CT), a calcium-regulating hormone, was examined. The endo-beta-N-acetylglucosaminidase from Arthrobacter protophormiae (Endo-A) transglycosylated the Man(6)-GlcNAc moiety from an ovalbumin-derived high-mannose type glycosyl asparagine, Asn(Man(6)-GlcNAc(2))-OH, to a calcitonin derivative, [Asn(GlcNAc)(3)]-CT, in which the N-acetyl-d-glucosamine (GlcNAc) is attached to the third l-asparagine (Asn) residue of the peptide, and a calcitonin derivative containing a high-mannose type oligosaccharide, [Asn(Man(6)-GlcNAc(2))(3)]-CT, was synthesized. The optimal reaction conditions for the synthesis of [Asn(Man(6)-GlcNAc(2))(3)]-CT from Asn(Man(6)-GlcNAc(2))-OH and [Asn(GlcNAc)(3)]-CT catalyzed by Endo-A were examined. The transglycosylation yield relative to the concentration of the [Asn(GlcNAc)(3)]-CT added was 32.7%, and 4.42 mg of [Asn(Man(6)-GlcNAc(2))(3)]-CT was prepared.
The lentinan contents in the Lentinus edodes fruit body during storage were examined by ELISA method using anti-lentinan antibodies. The lentinan content (12.8 mg.g(-)(1) dw) before storage decreased to 3.7 mg.g(-)(1) dw over 7 days at 20 degrees C. However, it only slightly decreased at 1 degrees C and only decreased to 9.3 mg. g(-)(1) dw at 5 degrees C. Glucanase activity, which seems to be associated with lentinan degradation, increased more during storage of L. edodes at 20 degrees C than it did at lower temperatures. In addition, only glucose was detected as a degraded product from lentinan by the glucanase. This suggested that this enzyme would fit the profile of an exo-type glucanase. Also, polyphenol oxidase activity, known as an index of freshness reduction in the mushroom, increased approximately 2.7-fold (to 61.5 units.mg(-)(1)) over 7 days during storage at 20 degrees C. However, its activity changed little during storage at lower temperatures. These results indicate that the reduction during storage of the quality of L. edodes as a functional food is accompanied by the decrease of lentinan, and by browning, and that exo-glucanase plays an important role in the decrease of lentinan content.
Cationic liposomes containing the human interferon-beta (IFN-beta) gene induce marked growth inhibition in human glioma cells. In vivo experiments using an human glioma implanted into the brains of nude mice have demonstrated a definite growth-inhibitory effect, achieving complete tumor regression with multiple intratumoral injections of the gene. However, nude mouse studies are inadequate to evaluate antitumor effects fully, especially those related to activation of the host immune response. This article aimed to investigate antitumor effects and immune response activation by murine IFN-beta gene transfer in syngeneic mice. In vitro experiments demonstrated a stronger growth-inhibitory effect of liposomes containing the murine IFN-beta gene on a GL261 mouse glioma cell line than exogenously added murine IFN-beta. In in vivo experiments, intratumoral administration of liposomes containing the murine IFN-beta gene resulted in a 16-fold reduction in the mean volume of residual gliomas in the brains of C57BL/6 mice and massive infiltration of cytotoxic T lymphocytes (CTL) within the residual tumor, while few CTL were infiltrated in controls including murine IFN-beta, empty liposomes, naked plasmid expressing murine IFN-beta, and liposomes containing beta-galactosidase gene. In addition, 40% of mice treated with liposomes containing the murine IFN-beta gene were completely cured. These findings indicated that activation of cellular immunity participates in antitumor effects in vivo together with direct effects of the IFN-beta gene.
BACKGROUND: Diffuse submucosal cysts of the stomach have been suggested as a predisposing condition for the development of gastric cancer, especially multiple cancers. We report here two cases of diffuse submucosal cysts of the stomach associated with multiple gastric cancers which were detected during endoscopic follow-up. METHODS AND RESULTS: The first patient was a 75-year-old man and the second patient was a 72-year-old man. In the first case, we performed an endoscopic examination every year and detected an advanced cancer and two early cancers on the fifth year of the follow up. Because one of these cancers was advanced, we examined the second patient endoscopically every six months. In this patient, we detected two early cancers after 1.5 years follow up. CONCLUSIONS: We suggest that patients with this disorder should be examined regularly by endoscopy for the detection of gastric cancer, preferably every six months.
A double-blind placebo-controlled cross-over trial was undertaken to evaluate the effect of antioxidant supplementation on maximal oxygen uptake during bicycling, 31-phosphorus nuclear magnetic response spectroscopy (31P-NMRS) detected muscle energy metabolism during plantar flexion and muscle fatigue evaluated by 1-s electrical stimulation at low (10 Hz) and high (50 Hz) frequency. Seven male triathletes received daily oral antioxidant supplementation in capsule form including 100 mg coenzyme Q10 (CoQ10), 600 mg ascorbic acid and 270 mg alpha-tocopherol or placebo over a 6-week interval. Serum concentration of CoQ10 was significantly higher in the antioxidant phase (1.80+/-1 microg x ml(-1), mean +/- SD) than control (0.9+/-0.21 microg ml(-1)) or placebo phase (0.9+/-0.3 microg x ml(-1)) (P<0.01). Maximal oxygen uptake was 63.8+/-3.0 ml x min(-1) x kg(-1) in the control phase, and did not change significantly in the antioxidant (67.6+/-10.8 ml x min(-1) x kg(-1)) or the placebo phase (61.9+/-4.5 ml x min(-1) x kg(-1)). The combined 31P-NMRS/low frequency fatigue test (plantar flexion of the foot) did not show differences in the gastrocnemius muscle pH (6.77+/-0.14), phosphocreatine reduction at the end of exercise (23+/-14% of rest) and half-time for recovery of phosphocreatine (33+/-12 sec) between the placebo and the antioxidant trial. No difference in muscle fatigue at 10 Hz electrical stimulation was found between the three phases. In conclusion, the results demonstrate no effect of antioxidative vitamin supplementation on maximal oxygen uptake, muscle energy metabolism or muscle fatigue in triathletes.
Anti-tumor active polysaccharide against Sarcoma 180 was isolated by DEAE-Sepharose CL-6B and Sepharose 4B column chromatography from the hot-water soluble fraction of the mycelium of liquid-cultured Agaricus blazei mill. This polysaccharide did not react with antibodies of anti-tumor polysaccharides such as lentinan, gliforan, and FIII-2-b which is one of anti-tumor polysaccharides from Agaricus blazei. Moreover, the analyses of 13C-NMR and GC-MS suggested that this polysaccharide was preliminarily glucomannan with a main chain of beta-1,2-linked D-mannopyranosyl residues and beta-D-glucopyranosyl-3-O-beta-D-glucopyranosyl residues as a side chain. This polysaccharide was completely different from the anti-tumor polysaccharide from fruiting body of Agaricus blazei, beta-1,6-glucan.