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M Kasai

Publications and source records attributed to M Kasai.

At least 37 records · Page 2Linked to original sources
PubMed2003

Essential microenvironment for thymopoiesis is preserved in human adult and aged thymus.

Normal human thymuses at various ages were immunohistologically examined in order to determine whether adult or aged thymus maintained the microenvironment for the T cell development and thymopoiesis was really ongoing. To analyze the thymic microenvironment, two monoclonal antibodies (MoAb) were employed. One is MoAb to IL-1 receptor (IL-1R) recognizing medullary and subcapsular cortical epithelial cells of normal infant human thymus. The other is UH-1 MoAb recognizing thymic epithelial cells within the cortex, which are negative with IL-1R-MoAb. Thymus of subjects over 20 years of age was split into many fragments and dispersed in the fatty tissue. However, the microenvironment of each fragment was composed of both IL-1R positive and UH-1 positive epithelial cells, and the UH-1 positive portion was populated with lymphocytes showing a follicle-like appearance. Lymphocytes in these follicle-like portions were mostly CD4+CD8+ double positive cells and contained many proliferating cells as well as apoptotic cells. Thus these follicle-like portions in adult and aged thymus were considered to be functioning as cortex as in infant thymus. Proliferative activity of thymocytes in the thymic cortex and the follicle-like portions definitely declined with advance of age, while incidence of apoptotic thymocytes increased with aging.

Adolescent↗
PubMed2003

Vitrification of human blastocysts using cryoloops: clinical outcome of 223 cycles.

BACKGROUND: The need to cryopreserve human blastocysts is increasing. The successful birth has been reported of a baby from a blastocyst vitrified using the cryoloop technique. The present study expands on this earlier report to confirm the effectiveness of this vitrification procedure. METHODS: In patients undergoing IVF at one of three clinics, supernumerary blastocysts on day 5 or 6 at various stages of development were vitrified using cryoloops. RESULTS: Of 725 vitrified blastocysts, 583 (80.4%) survived. After the transfer of 493 blastocysts in 207 cycles, 76 women (37%) became clinically pregnant. Among these women, 21 pregnancies ended in miscarriage, 23 healthy babies were born in 18 deliveries, and 37 pregnancies are ongoing. The survival rate of day 5 blastocysts (87%) was higher than that of day 6 blastocysts (55%), but implantation rates and pregnancy rates were not statistically significantly different. CONCLUSIONS: Clinical outcomes with 725 blastocysts and 207 transfers showed that vitrification using cryoloops is effective and practical for the cryopreservation of human blastocysts. Early blastocysts on day 5 seem to be the most suitable in terms of stage and age for cryopreservation, but developed and day 6 blastocysts can also be cryopreserved.

Adult↗
PubMed2002

Influence of dietary conjugated linoleic acid isomers on early inflammatory responses in male broiler chickens.

1. The influence of dietary conjugated linoleic acid isomer (CLA, 0 and 10 g/kg) on the metabolic and physiological responses to immune stimulation induced by a single injection of Salmonella enteritidis lipopolysaccharide (LPS) or repeated injections of LPS and Sephadex G-50 was determined in male broiler chicks. 2. In experiment 1, 10-d-old chicks were fed on experimental diets for 14 d and half of the birds fed on each diet were injected intraperitoneally with LPS (1.5 mg/kg body weight). In experiment 2,7-d-old chicks were fed on experimental diets for 18 d. Immune stimulation was started at 19 d old and continued for 5 d. Half of the birds fed on each diet were injected intraperitoneally with 0.25 mg/kg body weight of LPS at 19, 21 and 23 d of age, and with 250 mg/kg body weight of Sephadex at 20 and 22 d of age to stimulate the immune system. 3. In experiment 1, giving CLA prevented an increase in blood heterophil to lymphocyte ratio 7 h after a single injection of LPS, and increases in plasma ceruloplasmin and alpha 1 acid glycoprotein (AGP) 24 h after the injection, but not 7 h after the injection. CLA also prevented a decrease in food intake for 24 h after LPS injection. 4. In experiment 2, the CLA diet partially prevented reductions in body weight gain and weight gain to feed intake ratio caused by repeated injections of LPS and Sephadex. Feeding CLA prevented increases in plasma ceruloplasmin and AGP at 24 d of age caused by repeated injections of LPS and Sephadex, but not at 20 d of age. 5. These results suggest that feeding CLA alleviates some undesirable metabolic and physiological changes induced by immunological stimulation in male broiler chicks.

Animals↗
PubMed2002

Factors affecting toxicity, response and progression-free survival in relapsed patients with indolent B-cell lymphoma and mantle cell lymphoma treated with rituximab: a Japanese phase II study.

BACKGROUND: The aim of the study was to determine factors affecting the toxicity and efficacy of rituximab monotherapy in relapsed patients with indolent B-cell lymphoma and mantle cell lymphoma (MCL). PATIENTS AND METHODS: A total of 90 patients were enrolled and treated with rituximab infusions at 375 mg/m2 once weekly for 4 weeks. Central pathology review revealed that histologically, 81 patients had indolent B-cell lymphoma or MCL: 59 with follicular lymphoma, 17 with MCL, four with marginal zone lymphoma and one with lymphoplasmacytoid lymphoma. Of these, four were ineligible due to violation of other eligibility criteria. Pre-treatment variables affecting toxicities were analyzed for all 90 patients, and those affecting response and progression-free survival (PFS) were analyzed for 77 eligible patients with confirmed indolent B-cell lymphoma or MCL. The relationship between serum rituximab levels and efficacy was also analyzed for 66 eligible patients. RESULTS: Hematological toxicities (grade > or =3) occurred more frequently in females (P <0.05), and thrombocytopenia and leukopenia were more frequent in patients with high lactate dehydrogenase (LDH) levels (P <0.05). Non-hematological toxicities (grade > or =2) were more frequent in patients with extranodal disease or bone marrow involvement. The overall response rate (ORR) in patients receiving one prior chemotherapy regimen was higher than those receiving two or more regimens (P <0.05). The median PFS was shorter in MCL patients, in those with extranodal disease, or in those receiving two or more prior chemotherapy regimens (P <0.01). The PFS intervals of patients with higher serum rituximab levels (> or =70 microg/ml) immediately before the third infusion were longer than in other patients (P <0.01). CONCLUSIONS: Several prognostic factors and serum rituximab levels are useful for predicting the toxicity and efficacy of rituximab monotherapy.

Adult↗
PubMed2002

Analysis of mixed chimerism in patients after allogeneic stem cell transplantation using a capillary electrophoresis system.

We analyzed mixed chimerism (MC) after allogeneic stem cell transplantation (SCT) using a capillary electrophoresis system with four kinds of fluorescence-labeled primers for microsatellites (D3S1359, D6S89, ACTBP2, HGH). The sensitivities of all microsatellites were at least 3%. The present method is sufficiently rapid: only 3-4 h are needed to perform all the procedures. For analysis of MC in 30 patients who had undergone allogeneic SCT, heterozygosity of all microsatellites was over 88% and informativeness of ACTBP2 and HGH was over 73%. We analyzed MC using this technique to determine whether it was useful for prediction of the prognosis of 22 patients who had undergone allogeneic SCT. MC was more frequently observed in patients who were treated without total body irradiation (TBI) than in patients who were treated with TBI (p = 0.009). MC was also seen in a larger percentage of patients without acute graft-versus-host disease (p = 0.027). Six patients developed graft failure or relapse among 12 patients with MC. The graft failure or relapse was higher in patients with MC than in patients with complete chimerism (CC) (p = 0.009) especially if they were over 30 years of age (p = 0.0005). In contrast, graft failure or relapse was not higher in patients with MC compared with patients with CC under 30 years of age (p = 0.78). These results show that MC is an important predictive factor, especially in patients over 30 years of age.

Adolescent↗
PubMed2001

Fusariosis associated with pathogenic fusarium species colonization of a hospital water system: a new paradigm for the epidemiology of opportunistic mold infections.

We sought the reservoir of Fusarium species in a hospital with cases of known fusarial infections. Cultures of samples from patients and the environment were performed and evaluated for relatedness by use of molecular methods. Fusarium species was recovered from 162 (57%) of 283 water system samples. Of 92 sink drains tested, 72 (88%) yielded Fusarium solani; 12 (16%) of 71 sink faucet aerators and 2 (8%) of 26 shower heads yielded Fusarium oxysporum. Fusarium solani was isolated from the hospital water tank. Aerosolization of Fusarium species was documented after running the showers. Molecular biotyping revealed multiple distinct genotypes among the isolates from the environment and patients. Eight of 20 patients with F. solani infections had isolates with a molecular match with either an environmental isolate (n=2) or another patient isolate (n=6). The time interval between the 2 matched patient-environment isolates pairs was 5 and 11 months, and 2, 4, and 5.5 years for the 3 patient-patient isolate pairs. The water distribution system of a hospital was identified as a reservoir of Fusarium species.

Air Microbiology↗
PubMed2001

Site-dependent modulating effects of conjugated fatty acids from safflower oil in a rat two-stage carcinogenesis model in female Sprague-Dawley rats.

Modifying effects of dietary administration of conjugated fatty acids from safflower oil (CFA-S), rich in conjugated linoleic acid, on major organs were examined in the post-initiation stage of a two-stage carcinogenesis model in female rats. Groups of 21 or 22 F344 female rats were treated sequentially with 2,2'-dihydroxy-di-n-propylnitosamine (intragastrically, i.g.), 7,12-dimethylbenz[a]anthracene (i.g.), 1,2-dimethylhydrazine (subcutaneously) and N-butyl-N-(4-hydroxybutyl)nitrosamine (in drinking water) during the first 3 weeks for initiation, and then administered diet containing 1 or 0.1% CFA-S for 33 weeks. Further groups of animals were treated with carcinogens or 1% CFA-S alone, or maintained as non-treated controls. All surviving animals were killed at week 36, and major organs were examined histopathologically for development of pre-neoplastic and neoplastic lesions. The 1 and 0.1% CFA-S treatment significantly decreased the incidence and multiplicity of mammary carcinomas, though a clear dose response was not observed. In the urinary bladder, the incidence of papillary or nodular hyperplasia but not tumors was significantly increased in the 1% CFA-S-treated group. The results indicate that low dose CFA-S may find application as a potent chemopreventor of mammary carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed2001

Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription.

The Dnmt3a DNA methyltransferase is essential for mammalian development and is responsible for the generation of genomic methylation patterns, which lead to transcriptional silencing. Here, we show that Dnmt3a associates with RP58, a DNA-binding transcriptional repressor protein found at transcriptionally silent heterochromatin. Dnmt3a acts as a co-repressor for RP58 in a manner that does not require its de novo methyltransferase activity. Like other characterized co-repressors, Dnmt3a associates with the histone deacetylase HDAC1 using its ATRX-homology domain. This domain of Dnmt3a represents an independent transcriptional repressor domain whose silencing functions require HDAC activity. These results identify Dnmt3a as a co-repressor protein carrying deacetylase activity and show that Dnmt3a can be targeted to specific regulatory foci via its association with DNA-binding transcription factors.

Binding Sites↗
PubMed2001

Electron microscopic studies of the translin octameric ring.

Translin is thought to participate in a variety of cellular activities including chromosomal translocations, translational regulation of mRNA expression, and mRNA transport. It forms an octameric ring structure capable of sequence-specific binding of both DNA and RNA substrates. We have used electron microscopy and single-particle image analysis to generate a three-dimensional reconstruction of the Translin ring. The subunits appear to have two distinct domains that assemble to form an open channel with diameter of approximately 30 A at one end and approximately 50 A at the opposite end. In the presence of either DNA or RNA containing consensus binding sequences, the largest opening into the central cavity is filled with density. Strikingly, although Translin shows significant sequence homology to only one other protein, Translin-associated factor X, the quaternary organization and the dimerization of subunits in the ring are very similar to those observed for hexameric ring helicases. This suggests that many of the structures in DNA and RNA metabolism may have similar quaternary organization.

Algorithms↗
PubMed2001

Re-treatment of relapsed indolent B-cell lymphoma with rituximab.

The purpose of this study was to investigate the toxicity and the efficacy of re-treatment with rituximab, a chimeric mouse human anti-CD20 monoclonal antibody, in relapsed patients with indolent B-cell non-Hodgkin's lymphoma (NHL) who responded to rituximab in the previous phase I or phase II study. Thirteen patients with relapsed B-cell NHL, each of whom was confirmed to have Revised European-American Lymphoma Classification type II, 1-6 histology (indolent B-NHL), enrolled in this re-treatment study. All were re-treated with rituximab at 375 mg/m2 weekly for 4 consecutive weeks. Rituximab re-treatment was well tolerated with no grade 3/4 nonhematological toxicities, similar to that of the initial treatment. No patients developed detectable human anti-chimeric antibody. Partial responses were observed in 5 of 13 patients (38%; 95% confidence interval [CI], 14% to 68%); 6 patients showed stable disease and 2 showed progressive disease. Overall survival rate was 93% at 19 months of median follow-up after rituximab re-treatment. Median progression-free survival (PFS) after the re-treatment was 5.1 months (95% CI, 4.1 to 5.6 months), and the median PFS after the initial treatment was 8.2 months (95%CI, 5.9 to 11.3 months). Although rituximab re-treatment induced prolonged depletion of normal peripheral blood B cells in all patients, no significant decrease in serum immunoglobulin or complement level was observed. In conclusion, rituximab re-treatment was well tolerated, and it may produce a prolonged PFS in some patients with indolent B-cell NHL who showed initial response to rituximab.

Adult↗
PubMed2001

Cu2+ reveals amiloride-induced activation and blocking of non-selective cation channel in larval bullfrog skin.

The non-selective cation channel (NSCC) in the larval bullfrog skin contributes to the short-circuit current (SCC) across the skin. The effects of amiloride and acetylcholine on the SCC were examined in the presence or absence of Cu2+ to determine whether the amiloride binding site mediating activation or that mediating inhibition of the channel is blocked by Cu2+ and whether amiloride and acetylcholine share a common binding site on the NSCC. The skin of tadpoles raised in aldosterone was examined with K-Ringer present on the apical side to potentiate the SCC. Amiloride (10(-4) M) transiently increased SCC in the absence of Cu2+. Apical application of 500 microM Cu2+ increased the SCC. In the presence of Cu2+, amiloride decreased the SCC. In contrast, acetylcholine (1 mM) transiently increased SCC whether Cu2+ was present or not. These results suggest that there are two binding sites for amiloride on the NSCC, whereby the site that activates the channel is blocked by Cu2+ while the site that inhibits it is not, and that the binding sites for acetylcholine and amiloride may be different.

Acetylcholine↗
PubMed2001

Successful birth after transfer of vitrified human blastocysts with use of a cryoloop containerless technique.

OBJECTIVE: Clinical application of vitrification for the cryopreservation of human blastocysts. DESIGN: Clinical trial of vitrification of human blastocysts. SETTING: Private assisted reproductive technology clinic. PATIENT(S): Supernumerary blastocysts after fresh blastocyst transfer were vitrified for subsequent transfer. INTERVENTION(S): Culture of pronuclear embryos to the blastocyst stage in sequential media and subsequent vitrification of supernumerary blastocysts using a cryoloop technique. MAIN OUTCOME MEASURE(S): Clinical outcome after transfer of vitrified blastocysts. RESULT(S): A total of 60 vitrified blastocysts from 21 patients were warmed, and the survival rate at 2 hours after warming was 63%. Six clinical pregnancies were achieved after 19 transfers. One healthy baby was born, four pregnancies are ongoing, and one ended in miscarriage. CONCLUSION(S): Human blastocysts can be successfully vitrified by suspension on a small nylon loop and a direct plunge into liquid nitrogen. A delivery and ongoing pregnancies prove the safety of this method. This report documents the first successful pregnancy and delivery achieved by blastocyst vitrification using the cryoloop containerless technique.

Abortion, Spontaneous↗
PubMed2001

Increase in spontaneous action potentials and sensitivity in response to norepinephrine in dorsal root ganglion neurons of adjuvant inflamed rats.

To gain an understanding of the cellular mechanisms of hyperalgesia and spontaneous pain in adjuvant-induced chronic inflammation, we investigated the effects of nerve growth factor (NGF), which is known to increase in inflamed tissues and to cause hyperalgesia, on the spontaneous activities and norepinephrine-induced excitation of dorsal root ganglion (DRG) neurons. Intracellular recordings were obtained from freshly dissociated and cultured DRG neurons (<30 microm) from intact and adjuvant inflamed (AI) rats. Of more than 100 freshly dissociated DRG neurons from the intact rats, none produced spontaneous action potentials, whereas 23% of the neurons from the AI rats did. Spontaneous activities were induced in 34% neurons from intact rats when cultivated for one day with NGF. No neurons from the intact rats responded to norepinephrine (NE), irrespective of whether they were freshly dissociated or cultured with NGF. In contrast, 11% of neurons from the AI rats, both freshly dissociated and cultured without NGF, had a small depolarization in response to NE. The present results suggest that, in AI rats NGF plays an important role in inducing spontaneous activities in DRG neurons, but not in inducing sensitivity to NE.

Action Potentials↗
PubMed2001

Effects of PGE(2) on neurons from rat dorsal root ganglia in intact and adjuvant-inflamed rats: role of NGF on PGE(2)-induced depolarization.

The effects of prostaglandin E(2) (PGE(2)) on primary afferent neurons were studied by intracellular recording from small (<30 microm) dorsal root ganglion (DRG) neurons cultured for up to 3 days. PGE(2) (10(-9)-10(-5) M) depolarized 4-10% of neurons cultured with nerve growth factor (NGF) in intact rats. The percentage of neurons depolarized increased in a concentration dependent manner, while the average amplitude of the depolarization did not change with concentration. The threshold to evoke an action potential was decreased by PGE(2) (10(-9)-10(-5) M) with the maximum percentage at 10(-9) M, and this effect was also observed in neurons not depolarized by PGE(2). Whether a neuron was depolarized by PGE(2) was not related with its capsaicin (CAP) sensitivity. In addition, we examined whether NGF influences the PGE(2) response of neurons in adjuvant-inflamed young adult animals. Removal of NGF from culture medium did not change the percentage of neurons depolarized by PGE(2) in intact rats (20 and 18% for neurons cultured without or with NGF for 2-3 days, respectively). Adjuvant induced inflammation increased the percentage of neurons depolarized by PGE(2) to 38%, but this was not reversed by an addition of anti-NGF antibody to the culture medium, suggesting that NGF does not play a substantial role in the increase in sensitivity to be depolarized by PGE(2).

Action Potentials↗
PubMed2001

AS-924, a novel, orally active, bifunctional prodrug of ceftizoxime: physicochemical properties, oral absorption in animals, and antibacterial activity.

AS-924 is an oral prodrug of the antibiotic ceftizoxime (CTIZ), a parenteral use cephalosporin. This novel prodrug, produced by esterifying CTIZ with a lipophilic pivaloyloxymethyl (POM) group and introducing a water soluble L-alanyl group, is expected to increase the bioavailability and thereby, augment the antibacterial activity of CTIZ in vivo compared with existing prodrugs. To study the effect of the L-alanyl group in AS-924 on its bioavailability, the plasma concentration profiles of CTIZ in dogs were examined following the dosing of AS-924 and CTIZ-POM, in powder form, after pretreatment with the antacid ranitidine, and following the dosing of AS-924 after pretreatment with a gastrointestinal motility stimulant metoclopramide or suppressant scopolamine butylbromide. The absorption rate of AS-924 was constant under these different conditions due to its unique balance of lipophilicity and water solubility. CTIZ is as antibacterially active as pre-existing oral cephalosporins against Gram-positive clinical isolates, while being more active against all Gram-negative isolates-particularly Enterobacteriaceae and Haemophilus influenzae. A simulation model for the eradication profile of bacteria in computer programmed pharmacokinetic (PK) system was carried out to study the antibacterial action of CTIZ in human. CTIZ was proven to eradicate Streptococcus pneumoniae and H. influenzae effectively, while cefpodoxime (CPOD), the active moiety of CPOD proxetil, eradicated S. pneumoniae, but not H. influenzae. These results confirm that, AS-924 is a potent oral antibiotic and would be expected to be clinically effective and efficient.

Administration, Oral↗
PubMed2001

Synthetic study on novel immunosuppressant KF20444.

The two new synthetic routes to 6,7-dihydro-10-fluoro-3-(2-fluorophenyl)-5H- benzo[6,7]cyclohepta[1,2-b]-quinoline-8-carboxylic acid (1), a novel immunosuppressant KF20444, are described. The seven-membered ring construction from 2-[4-(2-fluorophenyl)phenyl]-3-(2-carboxyethyl)-4-chloromethyl-6-fluoroquinoline (17c) was achieved by intramolecular Friedel-Crafts reaction under acidic conditions as the key step. Subsequently, the oxidation of 4-chloromethyl group followed by reduction of carbonyl group on the seven-membered ring afforded 1. This route provides a new method for the synthesis of 1.

Biochemistry↗
PubMed2001

Effects of a liquid diet supplement containing structured medium- and long-chain triacylglycerols on bodyfat accumulation in healthy young subjects.

The effects of a liquid-formula diet supplement containing structured medium- and long-chain triacylglycerols (SMLCT) composed of medium- (10%) and long-chain (90%) fatty acids were compared with those of long-chain triacylglycerols (LCT) on bodyfat accumulation in 13 healthy male volunteers aged 18-20 years. The subjects were randomly assigned the SMLCT or LCT group. The subjects in each group received a liquid-formula diet supplement of the SMLCT or LCT, which provided 1040 kJ plus daily energy intake for 12 weeks. Mean energy intake containing liquid diet throughout the 12-week period did not differ between the SMLCT and LCT groups. Bodyweight of subjects in both groups increased slightly from the baseline throughout the 12-week period, but the differences were not significant. Rates of variation of bodyfat percentage were significantly lower in the SMLCT group than in the LCT group throughout the 12-week period. Comparisons between the SMLCT and LCT groups at baseline and 12 weeks showed no significant differences in any of the biochemical blood parameters. These results suggest that replacing LCT with SMLCT over long periods of time could produce bodyfat loss in the absence of reduced energy intake.

Adipose Tissue↗