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Biomedical subjects

S Kumagai

Publications and source records attributed to S Kumagai.

At least 19 recordsLinked to original sources
PubMed2006

Risk factors for dietary variety decline among Japanese elderly in a rural community: a 8-year follow-up study from TMIG-LISA.

OBJECTIVE: To examine the factors related to the decline of dietary variety among the rural community-dwelling Japanese elderly people and the implication on the planning of elderly people's nutritional improvement program in the future. DESIGN: A prospective cohort study during 8-year follow-up from 1992 to 2000. SETTING: This study was conducted in Nangai Village, a rural and mainly agricultural area of Akita Prefecture in the northern part of Honshu, one of four main islands in Japan. SUBJECTS: A total of 417 elderly people (160 men, 257 women) who completed interviews and food intake frequency surveys conducted in 1992, 1994, 1996, 1998, and 2000 were studied. METHODS: Dietary variety and variables potentially associated with dietary variety decline were identified from a face-to-face interview at the baseline and 8-year follow-up surveys. The dietary variety was measured using the dietary variety score (DVS), which covers the 10 main food groups in Japanese meals. RESULTS: During the 8-year follow-up, 36.2% of the subjects showed a decline in dietary variety. Health characteristics also change among the 8-year follow-up and these changes have an effect on the decline of dietary variety. Significant predictors for decline in dietary variety included loss of spouse, deterioration in self-perceived chewing ability, and decrease in intellectual activity score. CONCLUSIONS: Loss of spouse, deterioration in chewing ability, and decline in intellectual activity may increase the risk of decline in dietary variety in community-dwelling Japanese elderly people.

Activities of Daily Living↗
PubMed2006

Troglitazone inhibits cell growth and induces apoptosis of B-cell acute lymphoblastic leukemia cells with t(14;18).

Peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of the nuclear receptor superfamily, has been detected in several human leukemia cells. Recent studies reported that PPARgamma ligands inhibit cell proliferation and induce apoptosis in both normal and malignant B-lineage cells. We investigated the expression of PPARgamma and the effects of PPARgamma ligands on UTree-O2, Bay91 and 380, three B-cell acute lymphoblastic leukemia (B-ALL) cell lines with t(14;18), which show a poor prognosis, accompanying c-myc abnormality. Western blot analysis identified expression of PPARgamma protein and real-time PCR that of PPARgamma mRNA on the three cell lines. Troglitazone (TGZ), a synthetic PPARgamma ligand, inhibited cell growth in these cell lines in a dose-dependent manner, which was associated with G(1) cell cycle arrest and apoptosis. We also found this effect PPARgamma independent since PPARgamma antagonists failed to reverse this effect. We assessed the expression of c-myc, an apoptosis-regulatory gene, since c-myc abnormality was detected in most B-ALL cells with t(14;18). TGZ was found to dose-dependently downregulate the expression of c-myc mRNA and c-myc protein in the three cell lines. These results suggest that TGZ inhibits cell growth via induction of G(1) cell cycle arrest and apoptosis in these cell lines and that TGZ-induced apoptosis, at least in part, may be related to the downregulation of c-myc expression. Moreover, the downregulation of c-myc expression by TGZ may depend on a PPARgamma-independent mechanism. Further studies indicate that PPARgamma ligands may serve as a therapeutic agent in B-ALL with t(14;18).

Adolescent↗
PubMed2006

Thymic granulomatous lesions in pigs.

Rare cases of thymic granulomatous lesions were found in pigs. The lesions consisted of epithelioid cells, multinucleated giant cells, and lymphocytes. Such lesions also were observed in the mesenteric lymph nodes, spleen, kidney, and stomach. The cytoplasm of the majority of giant cells and some epithlioid cells was periodic acid-Schiff (PAS) positive. All cells were positive for vimentin, lysozyme, and desmin. Ultrastructurally, the giant cells were rich in organella and attached to adjacent epithelioid cells by membrane interdigitation. The cells included numerous coated vesicles and granules. No etiologic pathogen, including porcine circovirus type 2, was detected in the lesions. This is the rare case of idiopathic thymic granulomatous lesion in pigs.

Animals↗
PubMed2005

Comparative activities of glutathione-S-transferase and dialdehyde reductase toward aflatoxin B1 in livers of experimental and farm animals.

In order to gain a better understanding of the relative activities of glutathione-S-transferase (GST) and aldehyde reductase toward aflatoxin B1 (AFB1) in relation to the variation of species susceptibilities, we studied the in vitro cytosolic GST and reductase activities in liver tissues from male Fischer rats, ICR mice and golden hamsters, adult male rainbow trouts and female piglets. The GST activity was determined by incubating the liver cytosol with glutathione (GSH) and AFB1 in the presence of the hamster liver microsomes to metabolize AFB1 to AFB1-8, 9-epoxide. The reaction product, AFB1 and GSH conjugate (AFB1-GSH), was quantified with HPLC. The reductase activity was determined by incubating liver cytosol with AFB1-dialdehyde, followed by the quantification of the metabolic product, AFB1-dialcohol, with HPLC. All the animal species possessed the GST activities, and AFB1-GSH formed increasingly with the increase of the AFB1 concentration according to the model of first-order enzyme reaction kinetics. The V(max) and K(m) values of the GST activities in rodent species were higher and lower, respectively, than those in the trout and pig, being consistent with the relative susceptibilities to AFB1 of these animal species. However, no relationship was noted between the reductase activity and species susceptibility. Thus, the result of this study shows that GST toward AFB1, but not aldehyde reductase, is a determinant of the variation of species susceptibilities.

Aflatoxin B1↗
PubMed2005

Differences in heat resistance among pathogenic Yersinia enterocolitica depended on growth temperature and serotype.

To gain a better understanding about the effect of growth temperature on heat resistance of Yersinia enterocolitica, we determined decimal reduction times at 60 degrees C (D60-values) for O:3; O:5,27; O:8; and O:9 strains harboring virulence plasmid coding for Yersinia outer membrane protein and experimentally virulence plasmid-deleted strains after they were grown to stationary phase at 7, 25, or 37 degrees C. Bacteria were inoculated into Trypticase soy broth and were incubated at several temperatures. D60-values of O:3; O:5,27; and O:8 strains were larger when they were grown at 37 degrees C than at 7 or 25 degrees C, despite the presence or absence of virulence plasmids. However, similar D60-values were observed in O:9 strains, despite growth at 7, 25, or 37 degrees C. The results indicate two types of Y. enterocolitica strains, growth temperature-dependent and -independent, and a Yersinia outer membrane protein that is not directly involved in growth temperature-dependent heat resistance.

Bacterial Outer Membrane Proteins↗
PubMed2004

Effect of mutated transporters associated with antigen-processing 2 on characteristic major histocompatibility complex binding peptides: analysis using electrospray ionization tandem mass spectrometry.

A novel allele of transporters associated with the antigen-processing (TAP) 2 gene, TAP2*Bky2 (Val(577)), is significantly increased in Japanese patients with Sjögren's syndrome (SS), and has a strong association with SS-A/Ro autoantibody production in SS and autoantibody including anti-SS-A/Ro and anti-U1 RNP antibody in systemic lupus erythematosus (SLE). To determine the influence of this natural mutated TAP on peptides loaded onto MHC class I, we analyzed the repertoire of peptides loaded onto MHC class I on transfectants with TAP1 and TAP2 or mutated TAP2 by electrospray ionization tandem mass spectrometry (ESI-MS/MS). After comparison of the peptide profiles we identified three peptides from only mutated TAP transfectants. Moreover, one of these peptides is derived from snRNP A, which is a target for anti-U1 RNP antibody. To our knowledge this is the first report to show that the natural mutation of TAP2 changes the peptide profile loaded onto MHC class I molecules.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

The contribution of cardiorespiratory fitness and visceral fat to risk factors in Japanese patients with impaired glucose tolerance and type 2 diabetes mellitus.

It is still unclear as to how cardiorespiratory fitness and visceral fat accumulation contribute to coronary heart disease (CHD) risk factors in patients with diabetes mellitus. The purpose of the present study was to investigate whether cardiorespiratory fitness contributes to such risk factors independently of visceral fat accumulation. Two hundred Japanese patients (137 men and 63 women, aged 22 to 81 years) with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (type 2 DM) without any intervention and pharmacological therapy participated in a cross-sectional study. The levels of fasting insulin, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and resting blood pressure were assessed. Maximal oxygen uptake (V.o(2max)), an index of cardiorespiratory fitness, was predicted by a graded exercise test using a cycle ergometer. Visceral fat area (VFA) was measured by computed tomography scan. The criteria for abnormalities of the risk factors were determined according to the standard values for Japanese. All subjects were divided equally into the following 3 groups according to their fitness level: low-fit (V.o(2max) < 32 mL/kg/min in men, V.o(2max) < 26 mL/kg/min in women), mid-fit (32 < or = V.o(2max) < 36 in men, 26 < or = V.o(2max) < 30 in women), and high-fit (V.o(2max) > or = 36 in men, V.o(2max) > or = 30 in women). The association between fitness level and the prevalence of abnormal values for these parameters was analyzed by a multiple logistic regression model adjusted for age and VFA. The odds ratio (OR) and 95% confidence interval (CI) for the prevalence of hyperinsulinemia were significantly lower in the mid-fit (OR = 0.35, 95% CI, 0.16 to 0.78) and in the high-fit groups (OR = 0.40, 95% CI, 0.16 to 0.98) compared with the low-fit group. In addition, ORs for the prevalence of low HDL-C in the mid-fit and high-fit groups were significantly lower (OR = 0.35, 95% CI, 0.14 to 0.86; and OR = 0.19; 95% CI, 0.08 to 0.60, respectively) than in the low-fit group. These results suggested that cardiorespiratory fitness might be one of the predictors of metabolic abnormalities, especially in patients with hyperinsulinemia and low HDL-C, independent of visceral fat accumulation in Japanese patients with IGT and type 2 DM.

Adipose Tissue↗
PubMed2004

Activation-induced cytidine deaminase expression in follicular lymphoma: association between AID expression and ongoing mutation in FL.

Activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) gene. AID has been reported to be specifically expressed in the germinal center (GC). Follicular lymphoma (FL) cells are known to be exposed to GC reaction, as characterized by a high degree of SHM with some heterogeneity in terms of intraclonal microheterogeneity and antigen selection. The heterogeneity of SHM pattern in FL intrigued us to investigate the AID expression. AID expression was investigated in 19 FL materials consisting of 15 cases of FL fresh cells and four cell lines. In all, 10 fresh cells and three cell lines expressed AID, but the others did not. SHM was investigated in 12 fresh cells and four cell lines. The ongoing mutation was significantly different between AID-positive and AID-negative FL fresh cells (unpaired Student's t-test, P=0.047). Ongoing mutation was not seen in any of the cell lines. AID expression was associated with the ongoing mutation in FL fresh cells (two-tailed Pearson's coefficient correlation, r=0.899, P=0.01). The switch off of AID expression may start in the B-lineage differentiation stage counterpart of FL after optimizing SHM, indicated by the cessation of the ongoing mutation in AID-negative FL fresh cells.

Aged↗
PubMed2004

Occurrence of aflatoxin M1 in domestic milk in Japan during the winter season.

A total of 208 samples of commercial pasteurized milk gathered from retail outlets across Japan during the winter season were analysed for aflatoxin M1 (AFM1). Japan was divided into 11 regions from north to south, and nine to 45 milk samples from each region were randomly purchased between December 2001 and February 2002. Each milk sample was cleaned up by an immunoaffinity column, and AFM1 was quantified by liquid chromatography with fluorescence detection in four independent laboratories. The limit of detection of the method was 0.001 microg kg(-1). The identity of the putative AFM1 in milk sample was confirmed by the formation of AFM1 hemi-acetal with trifluoroacetic acid. Based on the results obtained with spiked samples (0.05 microg AFM1 kg(-1)), the mean recovery was 91.4%, the relative standard deviation for repeatability was 4.6%, and the relative standard deviation for reproducibility was 8.0% among four independent laboratories. AFM1 was detected in 207 (99.5%) of 208 milk samples at 0.001-0.029 microg kg(-1), with a mean of 0.009 microg kg(-1) and a 90th percentile of 0.014 microg kg(-1). No significant difference of the level of AFM1 contamination was observed among the regions.

Aflatoxin M1↗
PubMed2004

Modification of cytokine milieu by A2A adenosine receptor signaling--possible application for inflammatory diseases.

Pro-inflammatory cytokine TNF-alpha (TNF) production from in vitro lipopolysaccharide (LPS)-stimulated human peripheral blood CD14+ cells (PB-CD14) was inhibited by A2A adenosine receptor (AdoR) (A2AR) or beta2 adrenergic receptor (ADR) (beta2R) signaling in a concentration-dependent manner. These inhibitory effects were presumably mediated by the increase in intracellular cAMP. Furthermore A2AR agonist and beta2R agonist synergistically inhibited the TNF production of LPS-stimulated PB-CD14 cells. These results suggest that the anti-inflammatory effect of extracellular adenosine is, at least in part, due to the modification of the cytokine milieu via A2A signaling, and that the targeting of both A2AR and beta2R may have strong therapeutic potential for the inflammatory diseases.

Anti-Inflammatory Agents↗
PubMed2004

Quantitative nested reverse transcriptase PCR vs. real-time PCR for measuring AML1/ETO (MTG8) transcripts.

A quantitative nested reverse transcriptase polymerase chain reaction (QN-RT-PCR) method was developed using a plasmid cDNA containing the AML1/ETO (MTG8) fusion transcript from Kasumi-1 cells, an acute-myelogenous leukemia cell line with the t(8;21) translocation. In this method, the plasmid was detectable at a concentration of 10(-17) m. The fusion transcript in a mixture of 10(7) Rice94 (Burkitt lymphoma cell line) cells containing two Kasumi-1 cells was detectable at 10(-17) m. In a previously published real-time PCR method, the plasmid containing the fusion transcript was detectable at 10(-16) m or higher, and 20 or more Kasumi-1 cells were detectable in 10(7) Rice94 cells. Thus, this QN-RT-PCR method is more sensitive than the real-time PCR. When the same samples were examined by real-time PCR and our QN-RT-PCR method, in one patient in clinical remission after chemotherapy and allogeneic-bone marrow transplantation (BMT), the transcript was detected by QN-RT-PCR 60 days prior to hematological relapse, in contrast to 10 days before hematological relapse by real-time PCR. The transcript level was below 10(-17) m (undetectable) with this QN-RT-PCR in patients in clinical remission after chemotherapy and BMT, while it was 10(-15)-10(-16) m in patients in clinical remission after chemotherapy alone. The quantitative difference of the transcript level in minimal residual disease (MRD) between these two different types of clinical remission was estimated to be at least 10(2)-fold. This QN-RT-PCR method is useful for predicting hematological relapse and for quantitatively estimating MRD in different types of clinical remission.

Cell Line, Tumor↗
PubMed2003

Phase I clinical and pharmacological study of intraperitoneal cis-bis-neodecanoato( trans- R, R-1, 2-diaminocyclohexane)-platinum II entrapped in multilamellar liposome vesicles.

PURPOSE: To perform a phase I study of intraperitoneal cis-bis-neodecanoato ( trans- R, R-1, 2-diaminocyclohexane)-platinum II entrapped in multilamellar vesicles (L-NDDP) for peritoneal carcinomatosis or sarcomatosis. METHODS: Eligible patients had normal renal, hematologic, and liver functions. Laparoscopy was performed on the first two courses for evaluation, adhesiolysis, and chemotherapy administration. Afterwards, chemotherapy was administered through a peritoneal catheter. Up to six courses were allowed. Peritoneal imaging with technetium-labeled sulfur colloid was used to determine adequate distribution prior to each course. Volunteering patients underwent pharmacokinetics studies during the second course. RESULTS: Fifteen of 16 registered patients, seven women and eight men (median age 53 years (range 26-76) and median performance status of 1) were assessable. Diagnoses were: malignant mesothelioma (six patients), signet ring cell (three), colon adenocarcinoma, pseudomyxoma peritonei, gastrointestinal stromal tumor (two each), and ovarian carcinoma (one). Median number of courses was two (range, one to six) Dose-limiting toxicity symptoms were fatigue and abdominal pain. Hematologic toxicities were minimal. Peri-operative complications included one colonic perforation requiring primary closure, a peritoneal catheter malfunction, a port site hematoma, and an ascites leak requiring re-suture. Five patients survived at least 3 years. Pharmacokinetics studies indicated a rapid but low absorption of drug into the systemic circulation, with a prolonged retention of platinum in the plasma compartment. Peritoneal L-NDDP exposure was 17 to 49-times greater than in the plasma compartment. CONCLUSIONS: Peritoneal cavity exposure to L-NDDP is prolonged, and systemic absorption is limited, yielding a high peritoneal/plasmatic ratio. The recommended dose for phase II studies is 400 mg/m2 every 28 days.

Adenocarcinoma↗
PubMed2003

Experimental murine hyalohyphomycosis with soil-derived isolates of Fusarium solani.

Two strains of soil-borne Fusarium solani, both characterized for their ability to produce cyclosporin A and C, were examined for their pathogenicity in severe combined immunodeficiency (SCID) and BALB/c male mice. Intravenous (i.v.) infections with F. solani conidia were performed. No mortality was observed after infection with 0.3-1.6 x 10(7) cfu per mouse in SCID and BALB/c mice. When mice were infected with 0.8-1.5 x 10(6) cfu per mouse and 2 days later with 1.2-1.9 x 10(6) cfu per mouse, 28.6-85.7% survival occurred over a 25-day period, depending on the F. solani strain and the inbred mouse line used. Death was preceded by renal insufficiency affecting both kidneys. Furthermore, i.v. injection with heat-killed conidia followed 2 days later by injecting viable conidia resulted in renal infection in both breeds of mice. F. solani isolated from infected organs was more virulent than the original isolate, and 3/8 (37.5%) of BALB/c and 4/7 (57.1%) of SCID mice died after receiving a single dose. Dissemination to the brain was found only in SCID mice, but torticollis was observed in both mouse breeds. Soil-borne F. solani isolates possess poor pathogenic potential for mice, but either two successive infective doses or a primary injection with heat-killed conidia followed by a single infective dose breaks through host defenses in normal and immunoincompetent mice. Mouse passage increased the pathogenicity of two soil-derived F. solani strains.

Animals↗
PubMed2003

Association of the TAP2*Bky2 allele with presence of SS-A/Ro and other autoantibodies in Japanese patients with systemic lupus erythematosus.

We previously reported that a new allele of transporter associated with antigen processing (TAP) 2 gene, TAP2*Bky2 (Val577), was significantly increased in Japanese patients with Sjögren's syndrome (SS) and had a strong association with SS-A/Ro antibody production. In the present study, it was investigated whether the association of TAP2*Bky2 with SS-A/Ro antibody production was also found in Japanese patients with systemic lupus erythematosus (SLE). Polymorphisms of the TAP1 and TAP2 genes were determined in 114 Japanese SLE patients by the polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) method. The allele frequencies of the TAP1 and TAP2 genes in SLE patients were not significantly different from those in controls, although the allele frequency of TAP2*Bky2 was slightly higher in SLE patients than in healthy control subjects (9.2% vs 5.5%, P = 0.126). The allele frequency of TAP2*Bky2 was significantly higher in SLE patients with oral ulcers than in those without. It was noteworthy that TAP2*Bky2 was significantly associated with the appearance of not only SS-A/Ro antibody but also SS-B/La, nRNP, and Sm antibodies in the patients. The association of TAP2*Bky2 was found with the antibody production to both 60 and 52kDa SS-A/Ro antigens. As TAP2*Bky2 had a strong linkage disequilibrium with DRB1*08032, TAP2*Bky2 or its haplotype with DRB1*08032 may be involved in SS-A/Ro antibody production not only in SS but also SLE patients, indicating that TAP2*Bky2 may be a susceptible gene not only to the disease of SS but also to the SS-A/Ro autoantibody production.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

A model to assess the risk of the introduction into Japan of the bovine spongiform encephalopathy agent through imported animals, meat and meat-and-bone meal.

The authors developed a mathematical model to assess the release risk of the bovine spongiform encephalopathy (BSE) agent into a country through the importation of live cattle, bone-in bovine meat and meat-and-bone meal (MBM) from the United Kingdom and other countries with BSE. Monte Carlo simulation was attempted using this model and input variables. The release risk in Japan, expressed as the weight of infected MBM released in Japan between 1993 and 2000, was estimated to be 23.4 kg to 53.8 kg. The simulation also indicated that imported MBM represented the most important risk factor for releasing the BSE agent into Japan. This paper also provides details of the first five cases of BSE detected in Japan between September 2001 and the end of 2002. In addition, the results of the investigation conducted to determine the source of infection and the measures taken by the Government of Japan to prevent the BSE agent from entering the food and feed chains are also outlined.

Animals↗
PubMed2003

Aflatoxin contamination in shrimp feed and effects of aflatoxin addition to feed on shrimp production.

One hundred fifty samples of shrimp feed were collected from the eastern and southern regions of Thailand, and aflatoxins B1, B2, G1, and G2 (AFB1, AFB2, AFG1, and AFG2) in them were analyzed. AFB1 contamination ranged from a nondetectable level (< 0.003 ppb) to 0.651 ppb. Metabolites of AFB1 were less abundant than AFB1. To study the effects of aflatoxin in feed on shrimp production, black tiger shrimp were divided into four groups of 30 shrimp per group, tested in triplicate, and fed diets containing 0 (control), 5, 10, or 20 ppb of AFB1 for 10 consecutive days. After 7 or 10 days of consumption on each diet, the shrimp were weighed and sacrificed for laboratory examination. AFB1 and its metabolites were not detected in shrimp muscle. The mortality rate was slightly higher in the AFB1-treated groups than in the control group. The body weight of the surviving shrimp was decreased to 46 to 59% of the initial body weight in the AFB1-treated groups but not in the control group. Histopathological findings indicated hepatopancreatic damage by AFB1 with biochemical changes of the hemolymph. These results show that aflatoxin contamination in shrimp feed may cause economic losses by lowering the production of shrimp. Feed contaminated at the level of 20 ppb or lower (i.e., at the observed natural contamination level) may pose a very low risk, if any, to human health.

Aflatoxins↗