High-dose therapy combined with peripheral blood stem cell transplantation for advanced low-grade follicular lymphoma: single-institution experience in Japan.
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Adult↗
Biomedical subjects
T Itoh
Publications and source records attributed to T Itoh.
Analysis of genetic changes in intrahepatic cholangiocarcinoma induced by thorotrast.
Thorotrast, a colloidal suspension of radioactive (232)ThO(2) that emits alpha particles, was used as a radiographic contrast agent in the 1930s-1950s. Several decades after injection, Thorotrast causes liver cancers, among which intrahepatic cholangiocarcinoma (ICC) is prominent. We investigated mutations of the RAS and the TP53 genes in archival sections of ICC induced by Thorotrast. Compared to ICC that was not associated with Thorotrast, the frequency of mutation of the KRAS gene was lower, while that of the TP53 gene was more than two times higher. The most common mutation of the TP53 gene was A-G transitions. Interestingly, TP53 mutations were also found in noncancerous areas of livers in which Thorotrast had been deposited. Furthermore, mutations tended to accumulate in tissues from more advanced tumors. These results suggest that deposited Thorotrast continuously damages DNA in liver cells in some way, resulting in A-G transitions of the TP53 gene. However, we have not been able to rule out the possibility that genetic insults occur indirectly in the proliferating cells adjacent to the necrosis rather than being a direct effect of alpha particles.
Aged↗
[Administration of docetaxel in cases of recurrent breast carcinoma with malignant pleural effusion controlled by intrapleural administration of OK-432].
Docetaxel is an anti-tumor agent which promotes the congregation and stabilization of microtubules, there by preventing cell division. It is reported to have anti-tumor activity against breast or non-small cell lung carcinomas which have been resistant to other anti-tumor agents. On the other hand, it causes peripheral edema and effusion in the pleural or peritoneal cavities. Thus, pleural or peritoneal effusions, which require drainage have been considered to be contraindications for the administration of docetaxel. OK-432 is an agent which causes adhesion by evoking a local inflammatory reaction. We experienced two cases of recurrent breast carcinoma with malignant pleural effusion. We successfully managed their pleural effusion with the intrapleural administration of OK-432. Thereafter, we safely administered docetaxel, and obtained good outcomes. The present paper also discussed the synergistic action between these agents.
Adenocarcinoma↗
Can bone marrow transplantation give the gift of a baby?
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Adolescent↗
[Detection of pyrazinamidase activity for differentiation of Campylobacter, Arcobacter, and Helicobacter spp. by using a high-performance liquid chromatography method].
A high-performance liquid chromatography method was investigated for the detection pyrazinamidase activity by Campylobacter, Arcobacter, and Helicobacter spp. Pyrazine carboxilic acid, one of the end products of pyrazinamide hydrolysis by microorganisms, was detected by using a high-performance liquid chromatography (HPLC). A loopful of organism colonies was emulsified in 0.5 ml of a 0.5% pyrazinamide solution. The suspens on was incubated in a 37 degrees C water bath for 18-20 hr. After centrifugation, the supernatant was analyzed by HPLC. This HPLC method does not require microaerobic incubation and was easy to interpret for strains with weak enzymatic activity. By this method, we tested 111 clinical isolates, type and reference strains of Campylobacter spp., Arcobacter spp., and Helicobacter spp. , C. jejuni, C. jejuni subsp. doylei, C. coli, C. upsaliensis, C. lari, C. lari (urease+), C. helveticus, C. hyolei, C. sputorum subsp. fecalis, C. gracilis, C. concisus, C. curvus were positive for pyrazinamidase. C. fetus subsp. fetus, C. hyointestinalis, C. sputorum subsp. sputorum, C. sputorum subsp. bubulus, C. mucosalis, A. butzleri, A. skirrowii, A. cryaerophilus, H. pylori, H. cinaedi, H. fennelliae, H. mustelae, H. felis, H. muridarum, H. canis, H. nemestrinae, H. pamentensis, H. pullourum were negative.
Amidohydrolases↗
Effect of water, saliva and blood contamination on bonding of metal brackets with a 4-META/MMA/TBB resin to etched enamel.
PURPOSE: To investigate the influence of contamination by water, human saliva, and blood on the bonding of metal brackets with a 4-META/MMA/TBB resin to etched enamel. MATERIALS & METHODS: For compressive shear bond strength measurements, the surfaces of bovine enamel were prepared either by etching with 37% phosphoric acid solution for 10, 30, or 60 s and then dried with oil-free compressed air for 10 s, or by contaminating with water, human saliva, and blood. Brackets were applied with Super Bond under loads of 200, 400, or 600 g. The bonded samples were immersed in water for 1 d or thermo-cycled for 500 cycles, and the mean shear bond strengths were compared using two-way ANOVA and Scheffé's multiple comparisons test at P = 0.05. RESULTS: The bond strengths to enamel etched for 60 s were independent of the variable load, regardless of the type of contamination. A short etching duration provided higher bond strengths than extended etching of samples contaminated with saliva and blood. The bond strengths to enamel etched for 10 s after thermal stress and immersion in water were from 11.4 to 30.4 MPa. The samples contaminated by saliva showed the lowest bond strength, and thermal stress did not reduce the bond strengths.
Acrylic Resins↗
Dipole source localization of ictal epileptiform activity.
Dipole source localization of ictal epileptiform activity recorded by scalp EEG was performed in patients prior to surgical treatment. The dipole tracing method combined with the scalp-skull-brain head model was used to locate epileptogenic foci. A digital EEG system was used for data collection. The accuracy of dipole source localization was evaluated by comparing the focus location with that obtained by chronic subdural electrocorticography. In a case of frontal lobe epilepsy with epileptogenic focus in the frontoparietal convexity, the results of dipole source localization agreed well with those obtained with chronic subdural electrocorticography. In a case of lateral temporal lobe epilepsy, the results of dipole source localization were consistent with those obtained with chronic subdural electrocorticography, but a small localization error was observed. The clinical usefulness of and suggestions for improving this method are discussed.
Adult↗
Activated endothelial cells induce apoptosis in leukemic cells by endothelial interleukin-8.
Tumor cells are eradicated by several systems, including Fas ligand-Fas and tumor necrosis factor (TNF)-tumor necrosis factor receptor (TNFR). In the previous study, we purified an apoptosis-inducing factor (AIF) to homogeneity from a medium conditioned by PDBu-treated HL-60 cells. N-terminal sequence analysis showed that AIF is identical to endothelial interleukin-8 (IL-8). A novel apoptosis system, in which endothelial cells participate via endothelial IL-8 release, is identified here. Human umbilical vein cells (VE cells) produce and secrete IL-8 by stimulation of IL-1alpha and TNF-alpha. Endothelial IL-8, which is secreted from VE cells by stimulation of IL-1alpha and TNF-alpha , induces apoptosis in myelogenous leukemia cell line K562 cells. Monocyte-derived IL-8 could not induce apoptosis in K562 cells. Moreover, interaction between VE cells and K562 cells induces the release of endothelial IL-8 from VE cells, and the attached K562 cells undergo apoptosis. Moreover, interactions between VE cell and other cell lines, such as HL-60, U937, Jurkat, and Daudi, induce the secretion of endothelial IL-8 and the induction of apoptosis in cell lines. Endothelial IL-8 significantly inhibits tumor growth of intraperitoneal and subcutaneous tumor mass of K562 cells and induces apoptosis in their cells in vivo. Endothelial IL-8 plays an important role in apoptosis involving endothelial cells, which may provide us with a new therapy for hematological malignancies.
Animals↗
Combining volume-weighted mean nuclear volume with Gleason score and clinical stage to predict more reliably disease outcome of patients with prostate cancer.
BACKGROUND: Various criteria for patients with prostate cancer have been reported to be of prognostic value, and we have reported that estimates of volume-weighted mean nuclear volume (MNV), developed by Gundersen and Jensen based on a stereological technique, accurately predict the prognosis of prostate cancer. However, all of these studies were conducted on cases in a single institution, and it has remained unclear whether MNV calculations obtained at one institution apply to cases at another institution. In attempting to solve this problem, we made a prognostic index (P.I.) based on data from one hospital, and tested whether these data could be used to predict the prognosis of patients at another hospital. MATERIALS AND METHODS: A retrospective, multivariate prognostic study of 195 patients with prostate cancer, diagnosed at Kyoto University Hospital and treated conservatively, indicated that clinical stage, Gleason score, and MNV were all significantly correlated with the prognosis of patients with prostate cancer. From the relative strengths of these prognostic factors in a multivariate analysis, the following P.I. was constructed: P.I. = Clinical stage x 1.8040 + Gleason score x 1.5245 + MNV x 2.3162 (the constants correspond to the risk ratio estimated by Cox analysis). The P.I. was calculated for 104 patients with prostate cancer diagnosed at Shizuoka City Hospital and treated conservatively for analysis of disease-specific survival. RESULTS: The prognostic index ranged from 3.841-16.142. Using the median value of 12.5 as a cutoff point, a clear separation of cases with poor and favorable prognosis was achieved (P < 0.0001, observation period: 1-167 months). CONCLUSIONS: The results of this study suggest that estimates of MNV can be evaluated at multiple institutions with the use of P.I. calculation. Furthermore, combining estimates of MNV with Gleason score and clinical stage predicts most powerfully disease outcome of patients with prostate cancer.
Aged↗
Phosphorylation of phospholipase Cgamma1 on tyrosine residue 783 by platelet-derived growth factor regulates reorganization of the cytoskeleton.
It is known that platelet-derived growth factor (PDGF) induces the phosphorylation of phospholipase C (PLC) gamma1 and that phosphorylation on tyrosine (Tyr) 783 of PLCgamma1 is essential for phosphatidylinositol 4,5-bisphosphate hydrolyzing activity in vivo, while phosphorylation does not affect the catalytic activity in vitro. To study the roles of Tyr-783 phosphorylation in vivo, we developed a polyclonal antibody that recognizes PLCgamma1 containing phosphotyrosine 783 (alpha-PLCgamma1 PY). Tyr-783-phosphorylated PLCgamma1 was not detected in the absence of PDGF, appeared after stimulation, increased for 30 min, and then decreased to near the prestimulation level. Immunostaining of cells showed that PDGF-produced Tyr-783-phosphorylated PLCgamma1 localized predominantly at membrane ruffles and stress fibers where it colocalized with actin filaments within 30 min. Ninety minutes after PDGF stimulation, the actin filaments were disassembled to short fragments, and the levels of Tyr-783-phosphorylated PLCgamma1 were remarkably decreased in membrane ruffles and cytoskeleton. Furthermore, the depolymerization of actin filaments and membrane ruffling caused by PDGF stimulation were blocked by microinjecting alpha-PLCgamma1 PY, as occurred following the microinjection of the PLCgamma1-2SH2 domain, which is expected to associate with phosphorylated PDGF receptors and to block PLCgamma1 binding. It is worth noting that the microinjection of tyrosine-phosphorylated peptide (consisting of 13 amino acids containing Tyr-783) induced the disassembly of actin filaments and membrane ruffling as observed in PDGF-stimulated cells, while nonphosphorylated peptide did not cause any effect. These data suggest that the phosphorylation of PLCgamma1 on tyrosine 783 by PDGF plays an important role in cytoskeletal reorganization in addition to mitogenesis.
3T3 Cells↗
Lysophosphatidylcholine upregulates CD40 ligand expression in newly activated human CD4+ T cells.
Lysophosphatidylcholine (lyso-PC) accumulates in tissues undergoing inflammation and atherosclerosis, where an infiltration of T cells is also seen. We found that lyso-PC increased IFN-gamma production and CD40L expression in CD4+ T cells stimulated with anti-CD3 Ab and recombinant CD80 molecules, whereas lyso-PC did not affect IL-2 and IL-4 production. These results suggest that lyso-PC, in combination with other stimuli, may regulate CD4+ T cell functions to propagate local inflammatory reactions and also imply a novel role played by a modified lipid in the selection of Th1/Th2 immune response as well as in the T cell mediated pathogenesis in atherosclerosis.
Antibodies↗
A novel phosphatidylinositol-5-phosphate 4-kinase (phosphatidylinositol-phosphate kinase IIgamma) is phosphorylated in the endoplasmic reticulum in response to mitogenic signals.
Here, we identify a novel rat phosphatidylinositol-5-phosphate 4-kinase, phosphatidylinositol-phosphate kinase IIgamma (PIPKIIgamma). PIPKIIgamma comprises 420 amino acids with a molecular mass of 47,048 Da, showing greater homology to the type IIalpha and IIbeta isoforms (61.1 and 63.7% amino acid identities, respectively) of phosphatidylinositol-phosphate kinase than to the type I isoforms. It is predominantly expressed in kidney, with low expression in almost all other tissues. PIPKIIgamma was found to have phosphatidylinositol-5-phosphate 4-kinase activity as demonstrated in other type II kinases such as PIPKIIalpha. The PIPKIIgamma that is present endogenously in rat fibroblasts, PC12 cells, and rat whole brain lysate or that is exogenously overexpressed in COS-7 cells shows a doublet migrating pattern on SDS-polyacrylamide gel electrophoresis. Alkaline phosphatase treatment and metabolic labeling in [32P]orthophosphate experiments revealed that PIPKIIgamma is phosphorylated in vivo, resulting in a shift in its electrophoretic mobility. Phosphorylation is induced by treatment of mitogens such as serum and epidermal growth factor. Immunostaining experiments and subcellular fractionation revealed that PIPKIIgamma localizes dominantly in the endoplasmic reticulum (ER). Phosphorylation also occurs in the ER. Thus, PIPKIIgamma may have an important role in the synthesis of phosphatidylinositol bisphosphate in the ER.
1-Phosphatidylinositol 4-Kinase↗
Vasorelaxant effect of olprinone, an inhibitor of phosphodiesterase 3, on mesenteric small artery and vein of rabbits.
The effects of olprinone, a cardiotonic agent that inhibits cyclic GMP (cGMP)-inhibited phosphodiesterase, was studied on isolated rabbit mesenteric small artery and vein. In the presence of indomethacin and propranolol, olprinone at concentrations of 10 nM to 10 microM and 1 microM to 100 microM relaxed norepinephrine-stimulated mesenteric artery and vein in a concentration-dependent manner, respectively. The relaxation was not endothelium-dependent in the artery. Removal of the endothelium, however, increased marginally the response of the vein to olprinone. Olprinone-induced relaxation was less pronounced in arteries contracted with high KCl solution + norepinephrine than in those contracted with norepinephrine alone. Nicardipine inhibited this attenuating effect of high KCl solution on the olprinone-induced relaxation. Olprinone (1 microM) enhanced the relaxation of artery and vein in response to a cAMP-increasing agent, 6-(3-dimethylaminopropionyl) forskolin (NKH477), but not to a cGMP- increasing agent, glyceryl trinitrate. Norepinephrine (10 microM) and caffeine (5 mM) elicited a transient, phasic contraction of the artery in Ca2+-free solution. Both olprinone and NKH477 attenuated more potently the norepinephrine-induced contraction than the caffeine-induced contraction. When norepinephrine (10 microM) and caffeine (5 mM) were successively applied in Ca2+-free solution, the contractile effect of caffeine was diminished compared to that in artery which had not been pretreated with norepinephrine. When the contraction in response to norepinephrine was partially attenuated by 1 microM olprinone, the following contraction evoked by caffeine was enlarged. It is concluded that olprinone relaxes the small artery more strongly than the vein via its direct action on smooth muscles. It is suggested that olprinone attenuates norepinephrine-induced contraction through inhibition of receptor-operated transmembrane Ca2+ influx and Ca2+ release from intracellular storage sites.
3',5'-Cyclic-AMP Phosphodiesterases↗
A comparison of Listeria monocytogenes serovar 4b isolates of clinical and food origin in Japan by pulsed-field gel electrophoresis.
Pulsed-field gel electrophoresis (PFGE) patterns of 102 L. monocytogenes serovar 4b isolates from patients and foods examined in Japan were compared with 16 isolates from foodborne listeriosis episodes which occurred in North America or Europe. Using a combination of PFGE patterns with the restriction enzymes SmaI, ApaI, AscI and Sse8387I, 82 clinical isolates from Japan were categorized into 45 PFGE types: the largest group of 17 isolates (20.7%) were of the same PFGE type as cultures from the large foodborne outbreaks which occurred in California (1985) and Switzerland (1983-1987). Twenty cultures from foods on retail sale in Japan were classified into 12 PFGE types: four isolates were of three PFGE types also recognized among isolates of clinical origin from Japan, including the predominant clinical type.
DNA Restriction Enzymes↗
Homonojirimycin isomers and N-alkylated homonojirimycins: structural and conformational basis of inhibition of glycosidases.
A series of natural epimers of alpha-homonojirimycin and its N-alkylated derivatives have been prepared to investigate the contribution of the different chiral centers and conformation of the specificity and potency of inhibition of glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin (1), beta-homonojirimycin (2), alpha-homomannojirimycin (3), beta-homomannojirimycin (4), alpha-3,4-di-epi-homonojirimycin (5), beta-4,5-di-epi-homonojirimycin (6), N-methyl-alpha-homonojirimycin (7), and N-butyl-alpha-homonojirimycin (8). Compound 1 was a potent inhibitor of a range of alpha-glucosidases with IC50 values of 1 to 0.01 microM. Compounds 2, 3, and 4 were surprisingly inactive as inhibitors of beta-glucosidase and alpha- and beta-mannosidases but were moderately good as inhibitors of rice and some mammalian alpha-glucosidases. Compound 4 was active in the micromolar range toward all alpha-glucosidases tested. Furthermore, compound 4, which superimposes well on beta-l-fucose, was a 10-fold more effective inhibitor of alpha-l-fucosidase than 1-deoxymannojirimycin (12) and 3, with a Ki value of 0.45 microM. Only compounds 5 and 6 showed inhibitory activity toward alpha- and beta-galactosidases (6with an IC50 value of 6.4 microM against alpha-galactosidase). The high-resolution structure of 1 has been determined by X-ray diffraction and showed a chair conformation with the C1 OH (corresponding to the C6 OH in 1-deoxynojirimycin) predominantly equatorial to the piperidine ring in the crystal structure. This preferred (C1 OH equatorial) conformation was also corroborated by 1H NMR coupling constants. The coupling constants for 7 suggest the axial orientation of the C1 OH, while in 8 the C1 OH axial conformation was not observed. The C1 OH axial conformation appears to be responsible for more potent inhibition toward processing alpha-glucosidase I than alpha-glucosidase II. It has been assumed that the anti-HIV activity of alkaloidal glycosidase inhibitors results from the inhibition of processing alpha-glucosidase I, but 1, 7, and 8 were inactive against HIV-1 replication at 500 microg/mL as measured by inhibition of virus-induced cytopathogenicity in MT-4 cells. In contrast, the EC50 value for N-butyl-1-deoxynojirimycin (11), which also inhibits processing alpha-glucosidase I, was 37 microg/mL. Compound 7 has been shown to be a better inhibitor of alpha-glucosidase I than 1 and 8 both in vitro and in the cell culture system. These data imply that inhibition of HIV by glycosidase inhibitors can be due to factors other than simply inhibition of processing alpha-glucosidase I.
1-Deoxynojirimycin↗
NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol depends on toxicity of each drug and NGF treatment schedule: in vitro study of adult rat sympathetic ganglion explants.
The simultaneous administration of nerve growth factor (NGF) has been found to prevent experimental neuropathies induced by anti-cancer drugs such as cisplatin, vincristine and taxol. However, it is clinically important to know whether NGF is beneficial once the neuropathy is already manifest. We established a bioassay system to examine the preventive effects of NGF in various treatment schedules. NGF significantly prevented the inhibition of neurite outgrowth by vincristine and taxol regardless of treatment schedules. The pre-treatment and co-treatment schedules were effective against cisplatin, but the post-treatment schedule was not. With regard to the neurite and nerve cell population densities, only the cisplatin group treated with NGF showed lower values than the control. These results indicate that NGF-treatment is effective for the toxic sympathetic nerve injury induced by vincristine and taxol regardless of the treatment schedule, but is not protective against cisplatin-induced nerve cell injury.
Analysis of Variance↗
Histone H1 binding does not inhibit transcription of nucleosomal Xenopus laevis somatic 5S rRNA templates.
It has long been proposed that selective binding of histone H1 is, in part, responsible for the differential developmental regulation of the oocyte and somatic 5S rRNA genes in Xenopus laevis. In this study we show that histone H1 binds both oocyte and somatic genes equally after reconstitution into mononucleosomes or oligonucleosome arrays. Furthermore, we show that the binding of histone H1 selectively represses only oocyte gene transcription and that an RNA polymerase III transcription complex is able to initiate transcription of nucleosomal somatic templates regardless of whether histone H1 is present. These results support a model in which the differential regulation of the 5S rRNA genes is not simply due to the prevention of histone H1 binding by transcription complexes on the somatic genes, but rather to a difference in the histone H1 interaction with the somatic and oocyte genes.
Acetylation↗
Phosphate group requirement for mitogenic activation of lymphocytes by an extracellular phosphopolysaccharide from Lactobacillus delbrueckii ssp. bulgaricus.
The mitogenic activity of extracellular polysaccharides produced by Lactobacillus delbrueckii ssp. bulgaricus OLL 1073R-1 and NCFB2483 was examined in murine lymphocytes. The extracellular polysaccharide from Lactobacillus delbrueckii ssp. bulgaricus OLL 1073R-1 was fractionated into neutral and acidic polysaccharides by anion-exchange chromatography, while that of Lactobacillus delbrueckii ssp. bulgaricus NCFB2483 were all fractionated into neutral polysaccharide(s). The acidic polysaccharide stimulated mitogenic responses of murine splenocytes and Peyer's patches but not of thymocytes. The optimal concentration of the acidic polysaccharide at the highest stimulation was 160 microg/ml. A significant increase of mitogenic activity was initiated at 24 h, and the highest response was obtained after stimulation for 48 h. The acidic polysaccharide purified by high performance liquid chromatography also had substantial mitogenic activity, and the molecular weight was estimated to be 1.2 x 10(6). The acidic polysaccharide was a phosphopolysaccharide consisting of glucose, galactose and phosphorus. Dephosphorylation by hydrofluoric acid degradation reduced the mitogenic activity in lymphocytes. The phosphopolysaccharide produced by Lactobacillus delbrueckii ssp. bulgaricus 1073R-1 is a potent B-cell-dependent mitogen in which the phosphate group acts as a trigger of the mitogenic induction.
Animals↗