Biomedical subjects

Y Sasaki

Publications and source records attributed to Y Sasaki.

At least 37 records · Page 2Linked to original sources

PubMed2005

Phase I and pharmacokinetic study of oral fludarabine phosphate in relapsed indolent B-cell non-Hodgkin's lymphoma.

BACKGROUND: The primary objective of this study was to investigate the tolerability, efficacy and pharmacokinetic profile of oral fludarabine phosphate in relapsed patients with indolent B-cell non-Hodgkin's lymphoma (B-NHL). PATIENTS AND METHODS: Patients received fludarabine phosphate orally for 5 days, for a total of one to three cycles. Tolerability was assessed using the National Cancer Institute Common Toxicity Criteria. Efficacy was assessed using the International Workshop Criteria for NHL. Pharmacokinetic samples were taken on day 1 and day 5 of the first treatment cycle. RESULTS: Twelve patients were enrolled. One patient at 40 mg/m2/day developed grade 4 hyperuricemia. At 50 mg/m2/day, one patient developed grade 3 febrile neutropenia and grade 4 leukopenia, and another patient showed lasting grade 4 neutropenia. Most common toxicities included grade 3 or 4 lymphopenia (83%), leukopenia (50%) and neutropenia (50%). All the toxicities were reversible. The overall response rate was 67%. The AUC0-24h values on day 5 indicated a dose-dependent increase in systemically available 2-fluoro-arabinofuranosyl-adenine (2F-ara-A). CONCLUSIONS: Oral fludarabine phosphate is safe and effective for relapsed patients with indolent B-NHL. The dose of 40 mg/m2/day is recommended for a following pivotal phase II study.

Administration, Oral↗

PubMed2005

A ninety-day oral toxicity study of a new type of processed gum arabic, from Acacia tree (Acacia senegal) exudates, in F344 rats.

This study was designed to evaluate and characterize any subchronic toxicity of a new type of gum arabic (SUPER GUM [Acacia(sen)SUPER GUM]), a naturally processed polysaccharide exudate from gum acacia trees (Acacia senegal), when administered to both sexes of F344 rats at dietary levels of 0 (control), 1.25%, 2.5%, and 5.0% (10 rats/sex/group). During the study, the treatment had no effects on clinical signs, survival, body weights, and food and water consumption, or on findings of urinalysis, ophthalmology, hematology, or blood biochemistry. Gross pathology and histopathology exhibited no differences of toxicological significance between control and treated rats. Increased relative cecum (filled) weights, evident in both sexes of 5.0% group and females of 1.25% and 2.5% groups, were considered to be a physiological adaptation. Thus, the results indicated the toxic level of SUPER GUM to be more than 5.0%, and the no observed adverse effect level (NOAEL) was concluded to be 5.0% (3,117 mg/kg body weights/day for males, and 3,296 mg/kg body weights/day for males) from the present study.

Administration, Oral↗

PubMed2005

Effects of ketamine and propofol on inflammatory responses of primary glial cell cultures stimulated with lipopolysaccharide.

BACKGROUND: Ketamine has been reported to exert anti-inflammatory effects on macrophages stimulated with lipopolysaccharide (LPS) in vitro and in vivo. Several studies have reported conflicting results regarding the effects of propofol on cytokine production from immune cells. However, there have been no reports of the effects of these agents on inflammatory responses in glial cells. We investigated the effects of ketamine and propofol on LPS-induced production of nitric oxide, tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) from primary cultures of rat glial cells in vitro. METHODS: Glial cells were stimulated with LPS in the absence and presence of various concentrations of ketamine (30-1000 microM) or propofol (30 and 300 microM). Nitric oxide released into the culture media was determined by measuring nitrite using the Griess reaction, and concentrations of TNF-alpha and PGE(2) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Ketamine reduced LPS-induced TNF-alpha production without significant inhibition of nitrite release in mixed glial cells, astrocyte cultures and microglial cultures. Ketamine also inhibited LPS-induced production of PGE(2) in astrocyte cultures. In contrast, propofol had no effect on LPS-induced nitrite or TNF-alpha production in mixed glial cells. CONCLUSIONS: The data demonstrate that ketamine inhibited some of the inflammatory responses of both astrocytes and microglial cells treated with LPS without causing major change in nitric oxide release. Propofol had no effect on the production of nitric oxide or TNF-alpha from LPS-stimulated glial cells.

Anesthetics, Dissociative↗

PubMed2005

Suppressing actions of butyrate on growth hormone (GH) secretion induced by GH-releasing hormone in rat anterior pituitary cells.

We assessed the inhibitory effects of butyrate on the growth hormone (GH) secretion in order to investigate the cellular mechanisms in rat somatotrophs. Isolated anterior pituitary cells were cultured in DMEM for several hours, either in the presence (1, 3, or 10mM) or absence of butyrate, and then stimulated with 10(-7)M GHRH for 30 min, in the presence of butyrate at the concentrations used for the previous culture. The increase in GHRH-induced GH release was significantly reduced in a time-dependent and concentration-dependent manner in the cells previously cultured with butyrate. GH content (the sum of GH released into the medium induced by GHRH stimulation and the GH remaining in the cells after stimulation) was reduced by the culture of cells in the presence of butyrate, which was also inversely dependent on the concentrations used for the culture. Simultaneous addition of an L-type Ca(2+) channel blocker, nifedipine (10 pM), to the medium during 10(-9)M GHRH stimulation significantly reduced the stimulated GH release, which was further significantly decreased by a simultaneous addition of 10 mM butyrate. Butyrate blunted the GHRH (10(-9)M)-induced increase in cellular cyclic AMP and calcium ion concentrations, the activity of protein kinases (A and C), and GHmRNA expression. The expression of mRNA for GPR 41 and 43, known as receptors for short-chain fatty acids, was confirmed in the anterior pituitary cells. These findings suggest that butyrate inhibits GHRH-induced GH release as well as GH production, and the cellular inhibitory actions of butyrate occur in diverse cellular signaling pathways of rat somatotrophs.

Animals↗

PubMed2005

Effect of calcium trisodium DTPA in rats with puncture wound contaminated by 90Y-chloride.

The efficacy of diethylenetriaminepentaacetate calcium trisodium (CaNa(3)DTPA) in a dose of 34.7 micromol kg(-1) as a function of its route of administration was investigated in rats with a puncture wound contaminated by (90)Y-chloride at a concentration of 2.55 MBq kg(-1). Approximately 60% of (90)Y-chloride at a puncture wound was absorbed into the body of rats over 72 h post-puncture and radioactivity in femoral bone increased during the timed-release of (90)Y. Intravenous administration of CaNa(3)DTPA (systemic treatment) at 15 min post-puncture reduced (90)Y at a puncture wound and in bone up to 75.6 and 84.3% of controls, respectively. Direct infiltration of CaNa(3)DTPA into a puncture wound site (local treatment) at 15 min post-puncture diminished radioactivity at the puncture wound and in bone up to 34.9 and 52.5% of controls, respectively. Thus, prompt local treatment may be effective for removing (90)Y from a puncture wound and minimising (90)Y-distribution to bone compared with systemic treatment.

Animals↗

PubMed2005

Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours.

Hypoxia is a key factor contributing to the progression of human neoplasias and to the development of resistance to chemotherapy. BNIP3 is a proapoptotic member of the Bcl-2 protein family involved in hypoxia-induced cell death. We evaluated the expression and methylation status of BNIP3 gene to better understand the role of epigenetic alteration of its expression in haematopoietic tumours. Methylation of the region around the BNIP3 transcription start site was detected in four acute lymphocytic leukaemia, one multiple myeloma and one Burkitt lymphoma cell lines, and was closely associated with silencing the gene. That expression of BNIP3 was restored by treatment with 5-aza2'-deoxycytidine (5-aza-dC), a methyltransferase inhibitor, which confirmed the gene to be epigenetically inactivated by methylation. Notably, re-expression of BNIP3 using 5-aza2-dC also restored hypoxia-mediated cell death in methylated cell lines. Acetylation of histone H3 in the 5' region of the gene, which was assessed using chromatin immunoprecipitation assays, correlated directly with gene expression and inversely with DNA methylation. Among primary tumours, methylation of BNIP3 was detected in five of 34 (15%) acute lymphocytic leukaemias, six of 35 (17%) acute myelogenous leukaemias and three of 14 (21%) multiple myelomas. These results suggest that aberrant DNA methylation of the 5' CpG island and histone deacetylation play key roles in silencing BNIP3 expression in haematopoietic tumours.

Base Sequence↗

PubMed2005

Pinning of texture and vortices of the rotating B-like phase of superfluid 3He confined in a 98% aerogel.

We have investigated pinning effects on texture and vortices of the B-like phase of superfluid (3)He in a rotating aerogel up to +/-2pi rad/s by cw-NMR. We observed deformation of the NMR spectra in rotation, due to counterflow between the superflow and the normal flow. The average intensity of the counterflow was calculated from the change of NMR spectra. The rotation dependence of the counterflow intensity is similar to the magnetization curve of hard type II superconductors or the counterflow response of (4)He-II in packed powders. This counterflow behavior is in qualitative agreement with a model that vortices are pinned unless the counterflow exceeds a critical velocity v(c). The temperature independence of v(c) suggests that v(c) is associated with the expansion of primordial vortices.

Journal Article↗

PubMed2005

A 90-day oral toxicity study of beta-carotene derived from Blakeslea trispora, a natural food colorant, in F344 rats.

A subchronic oral toxicity study of beta-carotene derived from Blakeslea trispora, a natural food colorant, was performed with groups of 10 male and 10 female F344 rats fed the agent at dietary levels of 0%, 0.2%, 1.0% and 5.0% for 90 days. There were no treatment-related adverse effects with regard to body weight, food and water consumption, urinalysis, ophthalmology, hematology, serum biochemistry, and organ weight data. On clinical observation, red coloring of fur was noted in both sexes of the 1.0% and 5.0% group rats, with red feces observed in all treated group animals, and necropsy revealed all rats of the treated groups to have reddish coloration of the contents of the gastro-intestinal tract, due to the pigmentation and thus lacking toxicological significance. On histopathological examination, sporadic spontaneous lesions known to occur in this strain of rats were the only findings, with no specific relation to the test substance. Thus, the no-observed-adverse-effect-level (NOAEL) was judged to be a dietary level of at least 5.0% (3127 mg/kg body weight/day for males, 3362 mg/kg body weight/day for females) for beta-carotene derived from B. trispora under the present experimental conditions.

Animals↗

PubMed2005

Involvement of Rho-kinase in inflammatory and neuropathic pain through phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS).

Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major in vivo substrate for protein kinase C in the brain and has been implicated in cellular processes associated with cytoskeletal restructuring such as synaptic trafficking and neurotransmitter release. A phosphorylation-site specific antibody against Ser159-phospho-MARCKS (pS159-Mar-Ab) revealed that MARCKS is phosphorylated at Ser159 by Rho-kinase and that its phosphorylation is inhibited by the Rho-kinase specific inhibitor H-1152. Since the function of MARCKS is regulated by phosphorylation at multiple sites, here we examined the involvement of Rho-kinase in relation to phosphorylation of MARCKS at Ser159 in inflammatory and neuropathic pain by H-1152. When intrathecally administered 10 min before s.c. injection of formalin, H-1152 at 10 and 100 ng attenuated the second-phase, but not the first-phase, pain-like behaviors in the formalin test. Neuropathic pain induced by selective L5 spinal nerve transection was also relieved by intrathecal injection of H-1152. Nitric oxide synthase activity visualized by NADPH diaphorase histochemistry increased in the superficial layer of the spinal cord 30 min after formalin injection and 7 days after nerve transection, which were blocked by H-1152. Phosphorylation of MARCKS at Ser159 was detected in the spinal cord by pS159-Mar-Ab and the level of phosphorylation increased in the superficial layer after nerve transection. In contrast, immunoreactivities of neuronal nitric oxide synthase and MARCKS did not change significantly in the spinal cord before and after nerve transection. Taken together, the present study demonstrates that Rho-kinase is involved in inflammatory pain and the maintenance of neuropathic pain through phosphorylation of MARCKS at Ser159.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2005

Comparative studies on susceptibilities of two different Japanese isolates of Oncomelania nosophora to three strains of Schistosoma japonicum originating from Japan, China, and the Philippines.

Oncomelania nosophora (Gastropoda: Pomatiopsidae) is the intermediate host of Schistosoma japonicum in Japan. Although most of the snails were eliminated during the 20th century, they are still found in two areas in Japan. One area is in the Kofu Basin, including Nirasaki City, in Yamanashi Prefecture. The other is the Obitsu River Basin in Kisarazu City, Chiba Prefecture. Snails collected in Nirasaki and Kisarazu were exposed to 3 geographical strains of S. japonicum originating from Japan, China, and the Philippines. Both isolates of O. nosophora showed high susceptibility to the Japanese strain of S. japonicum (74.0% - 82.2%, for the Nirasaki isolate and 58.0% - 56.0% for the Kisarazu isolate) and low susceptibility to the Chinese strain (0.0% - 1.3% and 1.4% - 7.9% respectively). In contrast, the susceptibility of the snails to the Philippine strain was significantly different (P < 0.01) between the isolates (3.3% - 6.6% for the Nirasaki isolate and 31.9% - 75.9% for the Kisarazu isolate). To examine the differences in infectivity in detail, we conducted histological observations of snails exposed to the Philippine strain at 3 h, 1, 3, and 15 days after miracidial exposure. We found differences in the development of the parasite between the isolates of snails from early after exposure.

Animals↗

PubMed2005

The use of endoscopic ultrasound-guided fine-needle aspiration for investigation of submucosal and extrinsic masses of the colon and rectum.

BACKGROUND AND STUDY AIM: Ensdoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been reported as a useful technique for histological diagnosis of submucosal or extrinsic gastrointestinal and pancreatic lesions. The aim of this study was to evaluate the use of EUS-FNA for the diagnosis of lesions either within or adjacent to the wall of the colon and rectum. PATIENTS AND METHODS: A total of 22 patients with a lesion within the wall of, or adjacent to, the colon or rectum underwent EUS-FNA. They were divided into two groups: patients who had previously had a malignancy (the "previous +ve" group, n = 11), and patients who had not previously had a malignancy (the "previous -ve" group, n = 11). In the four patients who had lesions located proximal to the sigmoid colon, EUS-FNA was performed using a guide wire and overtube. The success rates for adequate tissue sampling and for detecting malignant and benign masses by EUS-FNA were evaluated and the success rate for detection was compared with the success rate of EUS and computed tomography. RESULTS: Sufficient tissue for evaluation was obtained from 21 of the 22 patients (95.5 %). The overall rate of detection of malignant and benign masses was 95.5 % (21/22) for EUS-FNA and 81.8 % (18/22) for pre-EUS-FNA imaging investigations. Of the 11 patients in the previous +ve group, ten were diagnosed with recurrences of primary malignancies; of the 11 patients in the previous -ve group, four were diagnosed with primary malignancies and seven were diagnosed with benign lesions. There were no complications related to the EUS-FNA procedure. CONCLUSIONS: EUS-FNA is a safe technique which is useful in the planning of treatment for patients who have a mass within the wall or adjacent to the wall of the entire length of the colon or rectum.

Adult↗

PubMed2005

Interferon sensitivity-determining region of nonstructural region 5A of hepatitis C virus genotype 1b correlates with serum alanine aminotransferase levels in chronic infection.

The mutations in the interferon (IFN) sensitivity-determining region (ISDR) of nonstructural region 5A (NS5A) of hepatitis C virus (HCV) have been correlated with response to IFN therapy. NS5A appears to disrupt a host antiviral pathway that plays a role in suppressing virus replication and protects hepatocytes from apoptosis. We assessed whether ISDR correlates with viral load and serum alanine aminotransferase (ALT) levels. Serum viral load and ALT levels were prospectively measured bimonthly by HCV core protein assay and monthly, respectively, for 22 months in 87 patients chronically infected with HCV genotype 1b. ISDR of HCV was directly sequenced from the products of reverse transcription and polymerase chain reaction of HCV RNA. Five patients had four or more substitutions (mutant type), 33 had 1-3 (intermediate type), and 49 had no substitutions (wild type) in ISDR. The numbers of substitutions in ISDR were inversely correlated with mean viral load over a 22-month period (r = 0.292, P = 0.0060) and directly with mean serum ALT levels (r = 0.360, P = 0.0006). The numbers of substitutions in ISDR was significantly larger in the patients with changes of viral load more than fivefold during the 22 months (1.4 +/- 2.4) than in those without changes (0.6 +/- 0.8) (P = 0.0188). The present study demonstrates that the patients with more substitutions in ISDR had significantly higher serum ALT levels and smaller viral load. These results suggest that NS5A with more substitutions in ISDR may lose the ability to block host antiviral pathways and to protect hepatocytes from apoptosis.

Adult↗

PubMed2005

Estimation of heritability for Tying-up syndrome in the Thoroughbred racehorse by Gibbs sampling.

Tying-up is a condition that primarily affects the muscles of horses. In this study, the heritability of the Tying-up syndrome in the Thoroughbred racehorse was estimated by Bayesian analysis with Gibbs sampling based on the threshold model for binary traits. The data used were the clinical data in racehorses diagnosed by veterinarians of the Racehorse Clinics of Japan Racing Association from 2000 to 2003. The health status of the Tying-up was treated as a binary trait. In the genetic analysis, the effect of changing the amount of the pedigree or inbreeding information on the estimation of heritability was investigated, too. The heritability estimates with non-zero probability in the posterior densities were approximately 0.16-0.18 in minimum, suggesting that the heritability of the Tying-up is not zero at least. The posterior density distributions of the heritability estimates were generally more pointed and sharp with using inbreeding coefficients than without using it, suggesting that more stable estimations were obtained when inbreeding coefficients were used. Among the different amounts of pedigree and inbreeding information, the heritabilities obtained with three or four generations of pedigree using inbreeding coefficients seems to be preferable, i.e. heritability of 0.42 or 0.43 for Tying-up.

Animals↗

PubMed2005

Genotype x environment interaction effects on carcass traits in Japanese Black cattle.

The importance of genotype x environment (region or management system) interactions for carcass traits in Japanese Black cattle was investigated using both univariate and multivariate animal models. The univariate approach was used mainly to test the significance of interaction effects. The multivariate approach was used to estimate genetic correlations, which indicated the magnitude of genotype x environment (GE) interactions. The more a genetic correlation deviates from 1, the larger the interaction. From the univariate approach, the addition of genotype x environment (region or management system) interaction (co)variance components resulted in an improved fit of the model for all traits in both cases (P < 0.001). However, estimates of genetic correlation between regions obtained from the multivariate approach for hot carcass weight, LM area, rib thickness, s.c. fat thickness, and marbling score were 0.97, 0.95, 0.93, 0.97, and 0.93, respectively. The corresponding estimates between management systems were 0.84, 0.92, 0.84, 0.90, and 0.97, respectively. These results indicate that GE interaction effects on carcass traits of Japanese Black cattle may be biologically unimportant. Therefore, breeding values obtained using the multivariate method would rank sires similarly in all environments. Consequently, carcass traits measured in these two different regions or management systems can be treated as the same traits.

Animal Husbandry↗

PubMed2005

Electron microscopic studies on the occurrence of activated neutrophils in peripheral blood of children with acute leukemias.

Peripheral blood (PB) cells are examined to assess cellular maturity and the degree of bone marrow abnormality in children with acute leukemias. During the ultrastructural assessments of PB cells in these children, we noted a frequent occurrence of activated neutrophils. This phenomenon had not been reported previously. We here report for the first time the identification of activated neutrophils in PB of children with acute leukemias. To examine the impact of activated neutrophils, we compared two groups of children including 18 with acute lymphoblastic leukemia (ALL) and 7 with acute myelogenous leukemia (AML) by an ultrastructural leukocyte count method. Many cases (50%) showed more than 30% activated neutrophils per total neutrophil count in PB. Activated neutrophils were elongated or amoeboid-shaped cells ranging from 13-18 microns in greater diameter with a decreased number of granules in the cytoplasm. A significantly higher rate of activated neutrophils was observed in ALL as compared with AML (median: 42.97% vs. 10.64%). Non-leukemic hospitalized (n =3) and healthy (n = 3) control cases showed a median rate of 3.32% activated neutrophils in PB. These findings reveal that a significantly high rate of activated neutrophils occurs in PB of children with ALL which may be exploited in the diagnostic assessment of children with acute leukemias.

Child↗

PubMed2005

Reduplicated basal lamina of the peritubular capillaries in renal biopsy specimens.

Reduplicated basal lamina of the peritubular capillaries (PTC) is usually found in kidney allografts in association with chronic transplant nephropathy and sometimes in native renal biopsies. In order to assess the incidence of this phenomenon in native renal biopsy specimens, we have carried out a retrospective review of the diagnostic ultrastructural pathology records of 80 consecutive renal biopsies excluding renal allografts and children with clinical signs of heavy proteinuria. Reduplicated basal lamina of the PTC was found in 19 out of the 80 cases (23.8%) with renal diseases. It was frequently seen in lupus nephritis, IgA nephropathy, and membranoproliferative glomerulonephropathy, being the subtypes of mesangial proliferative lesions. In a few cases it was also found in anti-neutrophil cytoplasmic autoantibody (ANCA) associated glomerulonephritis and benign nephrosclerosis renal biopsies. Reduplicated basal lamina of the PTC was strongly associated with glomerular and peritubular inflammation, and tubular necrosis. Peritubular interstitial edema, slight to moderately increased collagen fibrils, many spiraled collagen fibrils (indicative of degeneration), and collagen fibrils drawing from basal lamina were found around the reduplicated basal lamina of the PTC but not in normal basal lamina. These results indicate that in native renal biopsy specimens, reduplication of the basal lamina of the PTC is associated with endothelial cell injury and capillary permeability abnormality.

Adult↗

PubMed2004

Thymidylate synthase predictive power is overcome by irinotecan combination therapy with S-1 for gastric cancer.

The predictive values of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene expressions were retrospectively evaluated in patients with gastric cancer treated by a regimen containing S-1. The study population consisted of 53 patients registered into different two phase II studies for metastatic gastric cancer; 27 patients treated by S-1-alone study: 26 patients treated with S-1 combined with irinotecan (CPT-11). TS and DPD gene expressions in primary tumours were measured by the real-time reverse transcription PCR method. There was no statistical difference in DPD gene expression in terms of response in cases treated with S-1 alone and those treated with S-1 plus CPT-11. TS mRNA of responding tumours was lower than that of nonresponding ones when treated with S-1 (P<0.005). In the S-1-alone group, taking TS cutoff as the median values, the response rate in the low TS group was 50%, but only 8% in the high TS group (P<0.05). Patients with low TS gene expression survived longer than those with high TS gene expression (P<0.0001). However, there was no statistically significant difference in response rate and survival between patients with low TS tumours and those with high TS tumours, when the cutoff was taken as the median value of TS gene expression in the group treated with S-1 plus CPT-11. In conclusion, treatment effects of S-1 monotherapy for gastric cancer were determined by the status of TS gene expression, regardless of DPD gene expression. TS predictive power was overcome by CPT-11 combination therapy with S-1.

Adult↗

PubMed2004

Vortex formation and annihilation in three textures of rotating superfluid 3He-A.

Textures, textural transformation, and formation and annihilation of a single vortex were investigated in narrow cylinders with 100 microm radius in A-phase under rotation up to 6.28 rad/sec. Three textures were found, depending on the cooling conditions of the sample through the superfluid transition temperature T(c). We found the gyromagnetic effect of textures; that is, two textures (A or B) could be selected either by applying a magnetic field in parallel or anti-parallel to the rotation axis. The critical angular speed of a single vortex formation Omega(f) and that of annihilation Omega(a) for each texture were measured. The textural transformation in type A texture was induced by rotation. Both type A and B textures held macroscopic angular momentum along the rotation axis. We identified the texture for type A, B, and C as Mermin-Ho, radial disgyration, and a soliton type of defect along the axis, respectively.

Journal Article↗