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Biomedical subjects

K Itoh

Publications and source records attributed to K Itoh.

At least 361 records · Page 20Linked to original sources
PubMed1999

Changes in plasma apolipoprotein AI and AII concentrations in murine reactive amyloidosis.

Based on the recent findings that patients with systemic amyloidosis have reduced plasma apolipoprotein AII (apoAII) concentrations, this study assessed the behaviour of apolipoprotein AI (apoAI) and apoAII in a murine model of reactive amyloidosis. ICR mice were subjected to a single inflammatory stimulus and then sacrificed at the end of week 1 (group I), week 2 (group II) or week 8 (group III). Amyloid deposits were found in approximately one-half of the animals. Plasma apoAI and apoAII concentrations were reduced in all stimulated animals compared with control animals. In groups II and III, apoAII and apoAII/apoAI ratios were lower in the amyloidotic animals than in nonamyloidotic animals, similar to findings in the human amyloidosis patients. Both apoAI and apoAII mRNA in the liver were reduced in group I, but not in group II or III. Both apoAI and apoAII were detected immunohistochemically in the amyloid deposits in groups I and II, but not in group III. Thus, the reduction of plasma apoAs in the amyloid-forming phase may be due, in part, to the involvement of high-density lipoproteins in the deposits. However, that in the chronic phase may be affected by other mechanisms.

Amyloidosis↗
PubMed1999

Analysis of tumor necrosis factor-alpha production and polymorphisms of the tumor necrosis factor-alpha gene in individuals with a history of Kawasaki disease.

BACKGROUND: Tumor necrosis factor (TNF)-alpha plays a central role in the pathogenesis of vasculitis in Kawasaki disease (KD). To address the genetic background of KD, we investigated the level of TNF-alpha production and genetic polymorphisms in the 5' flanking region of the TNF-alpha gene in healthy children with a history of KD. METHODS: For TNF-alpha production, peripheral blood mononuclear cells (PBMC) of children with a history of KD (n = 61) and of non-KD children (n = 35) were stimulated with phorbol 12-myristate 13-acetate, toxic shock syndrome toxin-1 (TSST-1) and the culture supernatant of Staphylococcus aureus derived from a KD patient (S-6), which had several superantigenic activities. The genetic background of KD was addressed by studying polymorphisms in the 5' flanking region of the TNF-alpha gene at positions -1031 (thymine (T) to cytosine (C) change, termed -1031C), -863 (C to adenine (A), -863A), -857 (C to T, -857T), -308 (guanine (G) to A, -308A) and -238 (G to A, -238A) in KD, using dot-blot hybridization with sequence-specific oligonucleotide probes. RESULTS: The PBMC of KD patients with coronary artery lesions produced slightly higher levels of TNF-alpha in response to the bacterial products (such as TSST-1 and S-6). None of the polymorphisms in the 5' flanking region of the TNF-alpha gene were related to KD. CONCLUSIONS: These results suggest that a genetic disposition towards overproduction of TNF-alpha in response to bacterial products may be involved in the pathogenesis of KD.

Adolescent↗
PubMed1999

Expression of protein tyrosine phosphatase PTP-RL10 and its isoform in the mouse testis.

BACKGROUND: The cytoplasmic-type protein tyrosine phosphatase PTP-RL10/PTPD1/PTP2E contains an ezrin-like domain and associates with the c-Src protein tyrosine kinase. Because tyrosine phosphorylation regulated by protein tyrosine kinases and phosphatases is involved in activation, migration, differentiation and proliferation of various cell types, the expression of PTP-RL10 and c-src in the mouse testis was investigated. METHODS: Testes of wild-type mice and W/W(v) mutant mice that lack germ cells were analyzed by northern blotting, in situ hybridization histochemistry and reverse transcriptase-polymerase chain reaction for the expression of PTP-RL10, its isoform PTP-RL10b and c-src. Expression in the Sertoli cell lines, TM4 and TAMA26 was also analyzed. RESULTS: PTP-RL10 transcripts of 5.7kb and 2.9kb in size were detected in the testis. In situ hybridization histochemistry demonstrated that the 5.7kb transcripts were expressed in pachytene spermatocytes and somatic cells including Sertoli cells, in which c-src transcripts were detected. The 2.9kb transcript encoded a novel isoform, PTP-RL10b, that has the catalytic domain but not the domains that associate with c-Src. PTP-RL10b was expressed mainly in the testicular somatic cells. TM4 and TAMA26 cells were found to co-express PTP-RL10, PTP-RL10b and c-src transcripts. CONCLUSION: PTP-RL10 and its isoform are expressed in the Sertoli cells and are suggested to play roles in spermatogenesis by interacting with c-Src and/or other protein(s).

Animals↗
PubMed1999

Infection by an unenveloped DNA virus associated with non-A to -G hepatitis in Japanese blood donors with or without elevated ALT levels.

BACKGROUND: An unenveloped, single-stranded DNA virus named TT virus has been found in association with elevated alanine aminotransferase (ALT) levels in recipients of transfusions and has been detected frequently in patients with acute or chronic hepatitis of non-A to -G etiology in Japan. DNA of the TT virus was searched for in blood donors with or without elevated ALT levels. STUDY DESIGN AND METHODS: A total of 861 blood donors without previous transfusions and who were negative for markers of hepatitis B or C virus infection were tested. DNA of the TT virus was detected by polymerize chain reaction with hemi-nested primers. RESULTS: TT virus DNA was detected in 62 of 280 (22.1% [95% CI: 18.1-26.6]) donors with elevated ALT levels (mean +/- SD, 89.3 +/- 36.4 U/L; range, 61-301 U/L), which is significantly more frequently (p<0.02) than its detection in 91 of 581 (15.7% [95% CI: 13.2-18.4]) donors with normal ALT (< or = 45 U/L). The frequency of TT virus DNA increased with age, in donors with and without elevated ALT. CONCLUSION: The detection of TT virus DNA, at a frequency higher in donors with elevated ALT than in those without, strengthens the association of TT virus with non-A to -G hepatitis.

Adolescent↗
PubMed1999

Regulatory mechanisms of cellular response to oxidative stress.

An antioxidant responsive element (ARE) or electrophile responsive element (EpRE) mediates the transcriptional activation of genes encoding phase II drug metabolizing enzymes. The ARE consensus sequence shows high similarity to an erythroid gene regulatory element, and based on the observation, we have recently found that transcription factor Nrf2 is essential for the coordinate induction of phase II detoxifying enzymes. The expression of anti-oxidative stress enzyme genes is also regulated by Nrf2. Detailed analysis of the regulatory mechanisms of Nrf2 activity has ultimately led us to the identification of a new protein, which we have named Keap1, that suppresses Nrf2 activity by specific binding to its evolutionarily-conserved N-terminal Neh2 regulatory domain.

Animals↗
PubMed1999

Oxidative stress-inducible proteins in macrophages.

Macrophages produce reactive oxygen species such as O2-, H2O2 and *OH that contribute to the pathogenesis of diseases such as inflammation and atherosclerosis. The cells have multiple defense systems against those reactive oxygen species, and we describe here such an oxidative stress-inducible defense system. Upon exposure to reactive oxygen species and electrophilic agents, murine peritoneal macrophages induce stress proteins to protect themselves. Using differential screening, we cloned two novel proteins designated MSP23 and A170 that are induced in the cells by low levels of reactive oxygen species, electrophilic agents and other oxidative stress agents. MSP23 is murine peroxiredoxin I having a thioredoxin peroxidase activity and A170 is known as an ubiquitin- and PKC xi-binding protein. In addition to these two proteins, heme oxygenase-1 (HO-1) and cystine transport activity are also induced in the cells under oxidative stress conditions. Using nrf2-deficient macrophages, we found that transcription factor Nrf2, which is known to interact with antioxidant responsive elements (AREs) in the regulatory sequences of the genes, plays an important role in the oxidative stress-inducible response in the cells.

Animals↗
PubMed1999

Polymorphism of the 5'-flanking region of the tumor necrosis factor (TNF)-alpha gene and susceptibility to human T-cell lymphotropic virus type I (HTLV-I) uveitis.

The genetic background of human T-cell lymphotropic virus type I (HTLV-I) uveitis (HU) was investigated by studying the distribution of 5 polymorphisms of the 5'-flanking promoter/enhancer region of the tumor necrosis factor (TNF)-alpha gene in patients with HU, together with patients with adult T-cell leukemia (ATL), asymptomatic HTLV-I carriers, and healthy controls. The frequencies of the -1,031C allele (T-->C transition at position -1,031) and -863A allele (C-->A transition at position -863) in the HU patients, but neither in the ATL patients nor in the carriers, were significantly higher than those in the controls. The -1,031C and -863A alleles, in the absence of the HLA B61 or the DRB1*0901 allele which is in linkage disequilibrium with these alleles, were associated with increased susceptibility to HU. These results suggest that the -1,031C and -863A alleles might be genetic risk factors for HU.

Adult↗
PubMed1999

Dominant infiltration of T(H)1-type CD4+ T cells at the retrobulbar space of patients with thyroid-associated ophthalmopathy.

Lymphocyte infiltration in the retrobulbar space is a prominent histological feature of thyroid-associated ophthalmopathy (TAO). We have characterized phenotypic and functional features of T cells derived from retrobulbar infiltrates of 3 TAO patients to better understand their roles in the disease. One hundred four T-cell clones (TCC) were directly established from cells of retrobulbar tissues using a highly efficient cloning procedure. Phenotypic analysis of TCC showed approximately 70% to 80% were CD3+ CD4+ CD8- T cells, and approximately 20% to 30% were CD3+ CD8+ CD4- T cells. None of the TCC were CD3+ CD4- CD8- T cells. Analysis of the cytokine profile of TCC, as documented by the ability to express interferon-gamma, interleukin (IL)-2, IL-4, and IL-10 demonstrated that the majority of TCC expressed T helper (T(H))1-like profile in both the mRNA and protein levels. A few TCC showed T(H)0-like profile, but no TCC showed T(H)2-like profile. These results suggest that T(H)1-type CD4+ T cells play important roles in the pathogenesis of TAO.

Adult↗
PubMed1999

Co-expression of integrin-associated protein (IAP/CD47) and its ligand thrombospondin-1 on human granulosa and large luteal cells.

In the present study, we have raised a monoclonal antibody (mAb) designated OG-4 against human granulosa cells (GC). By immunohistochemistry, the expression of OG-4 antigen was observed on human GC and large luteal cells, but not on thecal and small luteal cells. A complementary DNA (cDNA) clone encoding OG-4 antigen was screened and isolated by a panning method using OG-4 mAb from a human corpus luteum (CL) cDNA library that was expressed transiently in COS-7 cells. Nucleotide sequencing revealed that OG-4 antigen was identical to integrin-associated protein (IAP)/CD47 antigen. Subsequent reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that the isoform 2 mRNA of IAP is predominantly expressed in human GC and CL. The expression of thrombospondin-1 (TSP-1), which is a ligand for IAP, was also observed in human GC by immunocytochemistry and RT-PCR. Co-expression of IAP and TSP-1 on human GC may suggest that TSP-1 has a physiological role in GC function possibly via IAP in an autocrine fashion.

Adult↗
PubMed1999

Expression of calcium binding protein D-9k messenger RNA in the mouse uterine endometrium during implantation.

To investigate the molecular mechanisms of implantation, we constructed a cDNA library of mouse uteri enriched with pregnancy-induced genes by subtractive hybridization and polymerase chain reaction (PCR). One of the isolated clones was the cDNA for the calcium binding protein D-9k (Cabp9k), which is considered to regulate intracytoplasmic concentration and transport of free calcium ions. Northern blot and in-situ hybridization analyses demonstrated that the Cabp9k mRNA was expressed in the endometrial epithelia, both luminal and glandular, in the uterus at the time of implantation. On pregnancy day 5 it was detected in the luminal, but not in the glandular, epithelia. In the oophorectomized adult mice, progesterone enhanced Cabp9k mRNA expression in the uterus, whereas oestrogen did not. Consistent with this, a nucleotide change was identified in the first intron of mouse Cabp9k gene corresponding to the oestrogen responsive element in the rat Cabp9k gene. Transfer of embryos into the uterine cavity of pseudopregnant mice reduced the expression of Cabp9k mRNA in the glandular epithelium, suggesting that Cabp9k mRNA expression is also regulated by embryonal signal(s). These findings demonstrated that Cabp9k mRNA is expressed in the endometrial epithelia during the implantation period under the control of progesterone and the presence of embryo, and suggest that CaBP9k plays a role in implantation by regulating the local calcium concentrations.

Amino Acid Sequence↗
PubMed1999

Recombinant human monoclonal Fab fragments against rotavirus from phage display combinatorial libraries.

We prepared and characterized human monoclonal Fab fragments to rotavirus from IgG1 kappa combinatorial libraries (designated as N and O) constructed from peripheral blood lymphocytes (PBLs) from two healthy individuals. Approximately 30-fold enrichment in eluted phage was obtained in these libraries after five rounds of panning against rabbit polyclonal antibody-captured human rotavirus (HRV) Wa strain. Forty-eight clones from each library were tested for reactivity to HRV Wa in an enzyme-linked immunosorbent assay (ELISA), and the identities of positive clones were determined by BstNI fingerprinting. As a result, eight individual clones (five from N library and three from O library) were isolated. In testing the cross-reactivity of Fabs against a panel of self- or non-self antigens, all Fab clones were found to be specific for HRV Wa. Fab clones from the two libraries showed distinct characteristics with respect to their reaction patterns with Wa and crossreactivities with rotavirus strains, and displayed variable heavy (VH) chain gene usage, although they recognized the VP6 protein as determined by immunoblotting. The distinct epitope recognition by Fabs from two libraries suggests different courses of humoral immune response to rotavirus during infection in the two individuals.

Amino Acid Sequence↗
PubMed1999

The available period and kind of exercise for increasing osteo sono assessment index in women.

PURPOSE: The purpose of this study is to determine the optimum period and kind of exercise which are more effective for increasing the calcaneus osteo sono assessment index (OSI) in adolescent women. METHODS: The subjects consisted of 600 female students aged from 19 to 21 studying at the Department of Food and Nutrition at Nakamura Gakuen University. The calcaneus OSI was measured by ultrasonic bone absorptiometry. The factors associated with an increased OSI were determined using piecewise linear regression analyses. RESULTS: Experience in performing impact-loading exercise either in junior high school or high school was found to be a significant predictive factor for increased calcaneus OSI after adjusting for age and weight. Regarding other exercise-related factors such as subjective intensity, frequency, hours at a time, and total duration of exercise, a piecewise liner regression analysis showed that a total duration of over 7 yr and a high subjective intensity of the impact-loading exercise during high school and junior high school periods caused a significant increase in the calcaneus OSI. However, the OSI decreased when the subjective intensity of the impact-loading exercise during the high school period was reported to be "very strenuous." CONCLUSIONS: Impact-loading exercise in junior high school and high school is important for increasing calcaneus OSI; however, impact-loading exercise in high school with a "very strenuous" subjective intensity was also found to possibly decrease the calcaneus OSI.

Adult↗
PubMed1999

Effects of intestinal bacteria on the development of colonic neoplasm: an experimental study.

Effects of intestinal microflora on the development of colonic neoplasm induced by 1,2-dimethylhydrazine (DMH) were observed using conventionalized and gnotobiotic mouse models. The incidence of colonic adenoma in germ-free mice (IQI/jic) (GF), mice conventionalized after DMH injection (Cvz-post-DMH) and conventionalized mice (Cvz, conventionalized before DMH injection) was 74%, 69% and 58%, respectively. The mean number of adenomas per mouse in the three groups was 2.6, 2.0 and 1.4, respectively. However, the adenoma in Cvz was larger than in GF. The incidence of adenoma in mice mono-associated with Mitsuokella multiacida, Clostridium butyricum, Bifidobacterium longum, Clostridium paraputrificum, Escherichia coli and Lactobacillus acidophilus was 68%, 68%, 63%, 50%, 50% and 30%, respectively. However, the adenoma in the Cl. paraputrificum group and the Cl. butyricum group was larger than in GF. Faecal pH in Cvz and the L. acidophilus group was significantly lower than in GF. The deconjugation rate of faecal bile acids in Cvz, the Cl. paraputrificum group and the Cl. butyricum group was significantly higher than in GF. These findings suggested two different effects of microflora on the development of DMH-induced adenoma: either an inhibition of the incidence of adenoma or a promotion of tumour growth. Effects of L. acidophilus may be mediated by faecal pH and effects of Cl. paraputrificum and Cl. butyricum by deconjugated bile acids.

1,2-Dimethylhydrazine↗
PubMed1999

Absence of cecal secondary bile acids in gnotobiotic mice associated with two human intestinal bacteria with the ability to dehydroxylate bile acids in vitro.

Germ-free mice were orally inoculated with human intestinal 7alpha-dehydroxylating bacterial strains to evaluate their ability to transform bile acids in vivo. Three weeks after inoculation of the bacteria, cecal bile acids were examined. Among free-form bile acids, only beta-muricholic acid was detected in the cecal contents of gnotobiotic mice associated with Bacteroides distasonis strain K-5. No secondary bile acid was observed in the cecal contents of any of the gnotobiotic mice associated with 7alpha-dehydroxylating bacteria, Clostridium species strain TO-931 or Eubacterium species strain 36S.

Animals↗
PubMed1999

Cytokines required for induction of histocompatibility leukocyte antigen-class I-restricted and tumor-specific cytotoxic T lymphocytes by a SART1-derived peptide.

Although there have been several reports on peptides of human tumor-rejection antigens capable of inducing histocompatibility leukocyte antigen (HLA)-class I-restricted and tumor-specific cytotoxic T lymphocytes (CTLs), it is not yet clear which cytokines are required for CTL induction. This study has investigated the cytokine combinations required for optimal induction of CTLs by SART1(690-698) peptide, which is capable of inducing HLA-A24-restricted and tumor-specific CTLs in peripheral blood mononuclear cells (PBMCs). Pretreatment of PBMCs as a source of antigen-presenting cells (APCs) with interferon (IFN)-gamma, or to some extent with IFN-alpha, but not with any of the other cytokines tested, augmented the peptide-induced CTL activity in HLA-A24 heterozygotes, but not in HLA-A24 homozygotes. This IFN-gamma-mediated augmentation was inhibited by either interleukin (IL)-4 or IL-10. IL-2 alone in culture, along with weekly stimulation by peptide-pulsed APCs, was sufficient for the differentiation and proliferation of CTLs for the initial several weeks of culture. This IL-2-mediated activation of CTLs was inhibited by the addition of IFN-gamma, IL-4, or IL-10 to the IL-2 culture. For further expansion of the CTLs, dendritic cells (DCs) induced from PBMCs with IL-4 and granulocyte macrophage colony-stimulating factor (GM-CSF) were required as APCs. These results indicate that IFN-gamma and IL-2 are important in the activation of APCs and CTLs, respectively, while GM-CSF and IL-4 are needed for the induction of DCs, which in turn are required for further expansion of mature CTLs. These results are important in allowing for a better understanding of the cellular and molecular basis of tumor-specific immunity, and also for the development of peptide-based specific immunotherapy.

Antigen-Presenting Cells↗
PubMed1999

[Non-Hodgkin's lymphoma complicated by recurrent intractable generalized herpes zoster responsive to long-term acyclovir therapy].

A 34-year-old male with a history of chickenpox developed primary abdominal non-Hodgkin's lymphoma (diagnosed in August 1995). Treatment with cyclophosphamide, doxorubicin, vincristine, and prednisolone achieved a partial remission. In July 1996, the disease recurred, and the patient received chemotherapy with carboplatine, etoposide, mitoxantrone, and prednisolone, but no response was noted. Involvement of the central nervous system and meninges was diagnosed on September 12, 1997. Blast cells were detected in the peripheral blood on September 26. Based on these findings, he was diagnosed as having leukemia. On September 27, painless vesicles developed on the left gluteal region. On October 13, the patient was hospitalized because the vesicles had spread over his entire body. Pathologic examination of the roofs of the blisters showed masses of inclusion bodies. Based on this, a diagnosis of varicella-zoster infection was made. Treatment with acyclovir (750 mg/day) for seven days failed to form crusts. New vesicles developed after the drug was discontinued, but crusts formed after acyclovir therapy was resumed. He died of interstitial pneumonia on December 21. Autopsy could not be performed. Histopathologic examination of pulmonary tissue obtained by necropsy did not reveal the presence of inclusion bodies characteristic of herpes simplex or varicella-zoster infection. Varicella-zoster virus (VZV) antigen was negative by an immunochemical staining method using monoclonal antibodies against VZV. Continuous long-term administration of acyclovir has been reported to be effective for non-Hodgkin's lymphoma complicated by recurrent intractable herpes zoster.

Acyclovir↗