Biomedical subjects

H Takimoto

Publications and source records attributed to H Takimoto.

At least 19 recordsLinked to original sources

PubMed2006

Folate intakes and folate biomarker profiles of pregnant Japanese women in the first trimester.

OBJECTIVE: To assess the status of dietary folate intake, serum and red blood cell (RBC) folate, and related nutritional biomarkers in healthy Japanese women in early pregnancy. DESIGN: A cross-sectional, observational study. SUBJECTS: Pregnant women in the first trimester, at 7-15 weeks gestation (n=70), who were not consuming any folate supplements or folate fortified foods. METHODS: Three-day dietary records were obtained from each subject to assess dietary folate intake. Blood samples were collected for measurement of biomarkers. Biomarkers and nutrient intake were analyzed in two groups defined by their serum folate concentrations: the low folate group (serum folate < 9 ng/ml) and the high folate group (serum folate > or = 9 ng/ml). RESULT: Mean serum and RBC folate concentrations in all subjects were 10.3 and 519 ng/ml, respectively. These levels were remarkably higher than the reported values from many other countries despite our subjects receiving no folic acids supplements. However, mean folate intake by our subjects from natural foods was 289 microg/day, which is thought to be low according to the Japanese dietary recommendation specified for pregnant women. The intake of spinach and fruits was significantly greater in the high folate group than in the low folate group. CONCLUSION: Folate intake was thought to be adequate to maintain a desirable level of serum folate concentration in Japanese pregnant women in the first trimester, although the intake of folate from natural food was not high enough to meet the recommended daily intake.

Adolescent↗

PubMed2006

Maternal weight gain ranges for optimal fetal growth in Japanese women.

OBJECTIVE: To identify adequate weight gain ranges during pregnancy in Japanese women. METHOD: Obstetric records from 2001 to 2002 for 46,659 term, singleton, vaginally delivered live births was used to estimate IUGR and macrosomia risk. Total maternal weight gain was grouped according to gestational age-specific percentile values of weight gain as follows: "very low" (under the 25th), "low" (25th to 49th), "moderate" (50th to 74th), "high" (75th to 89th), and "very high" (90th and over). RESULTS: About 6% of infants were identified as having IUGR and 0.9% as macrosomia. IUGR risk was elevated with low weight gains. Macrosomia risk was related to high weight gains and previous spontaneous abortions. CONCLUSION: Achieving weight gains between the 50th and 75th percentiles for gestational age was considered adequate for optimal fetal growth in Japanese pregnant women.

Adult↗

PubMed2006

Perceived body size and desire for thinness of young Japanese women: a population-based survey.

The present study describes findings in relation to perceived body size and 'desire for thinness' by age and residential areas ('metropolitan areas', 'large cities', 'small cities' and 'towns') among young Japanese women. Data on 1731 non-pregnant, non-lactating women aged 15-39 years from the 1998 National Nutrition Survey of Japan were used. Current body size was evaluated by BMI percentiles (lean, <5th; underweight, 5th or = BMI <25th; normal, 25th< or = BMI< 75th; overweight, 75th < or =BMI <95th; obese, > or =95th), calculated for 5-year age groups. Perceived body size was obtained by self-report. We defined 'overestimation' as non-overweight, non-obese women who perceived themselves as being 'overweight' or 'obese'. Desired body size was evaluated by applying the desired BMI to these cut-off points. Of all the women, 48.4% perceived themselves as being 'overweight' or 'obese', and 43.7% desired a 'lean' or 'underweight' body size. Adjusted for the current BMI, the OR for 'overestimation' calculated by a logistic regression model was significantly elevated in the 15-19-year age group (OR 2.79; 95% CI 1.76, 4.43), compared with the 25-29-year age group. The OR for 'desire for thinness' was significantly high in the 35-39-year age group (OR 2.74; 95% CI 1.93, 3.89) and the 15-19-year age group (OR 2.26; 95% CI 1.57, 3.24). Women living in metropolitan areas had higher OR for 'desire for thinness' (but not for 'overestimation') than did women in towns (OR 1.47; 95% CI 1.05, 2.07). The findings suggest the nature of excessive weight concerns of young women in Japan; thus efforts to control such health-risk behaviours at a national level are urgent.

Adolescent↗

PubMed2006

Interferon-gamma independent formation of pulmonary granuloma in mice by injections with trehalose dimycolate (cord factor), lipoarabinomannan and phosphatidylinositol mannosides isolated from Mycobacterium tuberculosis.

The mechanisms by which pulmonary granuloma formation is caused by administration of mycobacterial glycolipids such as trehalose dimycolate (TDM), lipoarabinomannan (LAM) and phosphatidylinositol mannosides (PIM) were investigated. When peritoneal and alveolar macrophages were stimulated with TDM, LAM and PIM in vitro, TDM exhibited the strongest tumour necrosis factor (TNF)-inducing activity. Responsiveness of macrophages from mice defected Toll-like receptor 4 (TLR4) was much higher than that of the wild-type mice. Although PIM and LAM also had a significant activity, LAM rather than PIM stimulated higher TNF-alpha production by alveolar macrophage. When mycobacterial glycolipids were injected as water-in-oil-in-water emulsion into mice via the tail vein, development of pulmonary granuloma in response to glycolipids were related closely to their TNF-inducing activity and TDM exhibited the strongest activity. Granuloma formation was observed not only in mice lacking interleukin (IL)-12 signalling but also interferon (IFN)-gamma knock-out mice. Granuloma formation caused by glycolipids correlated with TNF-alpha levels in lungs. Administration of anti-TNF-alpha monoclonal antibody into TDM-injected IFN-gamma knock-out mice decreased in granuloma formation, suggesting that development of pulmonary granuloma by mycobacterial glycolipids such as TDM is due to IFN-gamma-independent and TNF-alpha-dependent pathway.

Adjuvants, Immunologic↗

PubMed2003

Carbon dioxide insufflation for chronic subdural haematoma: a simple addition to burr-hole irrigation and closed-system drainage.

Burr-hole irrigation with closed-system drainage is a common surgical method used for chronic subdural haematoma. However, the subdural space with air that entered during surgery sometimes remains for a prolonged period after surgery and may hamper uncomplicated healing of the subdural space. We combined a simple procedure, insufflation of carbon dioxide (CO2) into the subdural space through a drainage catheter, with conventional burr-hole irrigation and closed-system drainage. By this additional procedure, both the subdural space and the gas within the space decreased rapidly, and the subdural drain could be removed within 24 h. By promoting obliteration of the subdural space, this simple combined technique may contribute to early recovery and discharge of patients, and to a reduction in the recurrence rate of the disease.

Aged↗

PubMed2001

Prediction of subsequent relapse in children with steroid-sensitive nephrotic syndrome.

Among nephrotic children with frequent relapses at risk for cumulative steroid toxicity, identification of children who may be at high risk for subsequent relapse is very important in making the decision to introduce cytotoxic drugs. We examined the clinical course of 467 relapses in 121 steroid-sensitive nephrotic children to elucidate the risk factors for subsequent relapse, using the Cox proportional-hazards regression model. Gender, age at onset, duration of illness from onset, prednisolone dosage at the most-recent relapse, and regimens of initial steroid therapy at onset were not associated with risk. Relapse within the 1st year was a powerful independent predictor of subsequent relapse irrespective of the duration of illness. The hazard ratio of patients with more than one relapse within the 1st year increased to 1.72-2.12 compared with those without a relapse within the 1st year. The remission period just before the most-recent relapse was also a significant predictor. The risk for patients with a 1-year or longer remission period decreased to 0.57. Patients treated with cyclophosphamide for 12 weeks had a significantly longer remission than those treated with prednisolone alone. Our results suggest that early relapse after onset and/or a short remission period just before recent relapse are independent risk factors for subsequent relapse. Cytotoxic therapy has serious adverse effects and its effect may be limited. Our results may be helpful in deciding on the suitability of cytotoxic drugs.

Adolescent↗

PubMed2001

Mycobacterial cord factor, but not sulfolipid, causes depletion of NKT cells and upregulation of CD1d1 on murine macrophages.

Trehalose 6,6'-dimycolate (TDM, cord factor) has frequently been used as an adjuvant to stimulate antibody production. Although it also induces cellular immunity, detailed studies about the underlying events do not exist. To determine the kinetics of TDM-specific changes promoting a T helper 1 (Th1) response, we injected mice with TDM or 2,3,6,6'-tetraacyl trehalose 2'-sulfate (SL, sulfolipid), another mycobacterial trehalose-containing glycolipid without mycolic acid. TDM, but not SL, caused a strong increase in serum interferon-gamma (IFN-gamma) levels 2 days later, accompanied by expansion of natural killer (NK) cells. Subsequent TDM effects included depletion of normal-density CD4(+) NK1.1(+) TCRalpha/beta(intermediate) cells from day 7 on, upregulation of MHC class II and CD1d1 on macrophages (peaking on day 21), and an increased proportion of Th1 cells evident after 3 weeks. TDM, but not a similar glycolipid without mycolic acid, can therefore initiate a cascade of events starting with strong release of IFN-gamma and NK cell expansion, resulting in the appearance of macrophages activated for antigen presentation. Our data therefore provide the basis for optimized immunization schedules with TDM as the adjuvant component of a Th1 vaccine.

Adjuvants, Immunologic↗

PubMed2001

Persistent infection with Listeria monocytogenes in the kidney induces anti-inflammatory invariant fetal-type gammadelta T cells.

After intraperitoneal inoculation with Listeria monocytogenes, gammadelta T cells appear in the peritoneal cavity preceding the appearance of alphabeta T cells. Such gammadelta T cells predominantly express T-cell receptor (TCR)Vgamma1/Vdelta6, develop through an extrathymic pathway, and contribute to host defence against the bacteria. We have observed a gradual increase in gammadelta T cells in kidneys of mice after intrarenal inoculation with L. monocytogenes, which resulted in an unusually long-lasting local infection. In this study, we examined the characteristics and the roles of the gammadelta T cells induced in this model. It was found that these gammadelta T cells predominantly expressed TCRVgamma6/Vdelta1 with canonical junctional sequences identical to those expressed on fetal thymocytes. Although depletion of such gammadelta T cells in vivo did not affect the number of bacteria, it resulted in histologically exacerbated inflammation in the kidneys. These results indicate that a persistent infection with L. monocytogenes in kidneys induces a different kind of gammadelta T cell from that induced after intraperitoneal infection. The former expresses invariant fetal-type Vgamma6/Vdelta1+TCR and plays a regulatory role in resolution of inflammation.

Animals↗

PubMed2001

[A case of suspected pulmonary air embolism in endoscopic neurosurgery].

Sudden reduction in end-tidal PCO2 and SpO2 occurred during the endoscopic third ventriculostomy in a patient with hydrocephalus under general anesthesia. We suspect that it was caused by pulmonary air embolism. A 63-year-old female was scheduled for endoscopic third ventriculostomy under general anesthesia. Endoscopic manipulation caused hemorrhage from chorioid plexus 21 minutes after the procedure was begun, and intraventricular irrigation was performed to achieve hemostasis. In the subsequent 3 minutes, end-tidal PCO2 declined from 26 mmHg to 15 mmHg (PaCO2 39.6 mmHg), and SpO2 declined from 98% to 92% (PaO2 69.2 mmHg). Nitrous oxide was discontinued immediately because pulmonary air embolism was suspected and the oxygen concentration was increased to 100%. At the same time the surgical procedure was discontinued. After 15 minutes, end-tidal PCO2 recovered to 25 mmHg, and SpO2 recovered to 98% (PaO2 136.5 mmHg), and surgery was resumed. The patient recovered from anesthesia. The chest X-p at the end of operation, and pulmonary scintigraphy on the following day revealed no abnormal findings, but brain CT demonstrated a large quantity of air in both lateral ventricles.

Embolism, Air↗

PubMed2000

Development of dendritic epidermal T cells with a skewed diversity of gamma delta TCRs in V delta 1-deficient mice.

One of the most intriguing features of gammadelta T cells that reside in murine epithelia is the association of a specific Vgamma/Vdelta usage with each epithelial tissue. Dendritic epidermal T cells (DETCs) in the murine epidermis, are predominantly derived from the "first wave" Vgamma5+ fetal thymocytes and overwhelmingly express the canonical Vgamma5/Vdelta1-TCRs lacking junctional diversity. Targeted disruption of the Vdelta1 gene resulted in a markedly impaired development of Vgamma5+ fetal thymocytes as precursors of DETCs; however, gammadeltaTCR+ DETCs with a typical dendritic morphology were observed in Vdelta1-/- mice and their cell densities in the epidermis were slightly lower than those in Vdelta1+/- epidermis. Moreover, the Vdelta1-deficient DETCs were functionally competent in their ability to up-regulate cytokines and keratinocyte growth factor-expression in response to keratinocytes. Vgamma5+ DETCs were predominant in the Vdelta1-/- epidermis, though Vgamma5- gammadeltaTCR+ DETCs were also detected. The Vgamma5+ DETCs showed a typical dendritic shape, gammadeltaTCR(high), and age-associated expansion in epidermis as observed in conventional DETCs of normal mice, whereas the Vgamma5- gammadeltaTCR+ DETCs showed a less dendritic shape, gammadeltaTCR(low), and no expansion in the epidermis, consistent with their immaturity. These results suggest that optimal DETC development does not require a particular Vgamma/Vdelta-chain usage but requires expression of a limited diversity of gammadeltaTCRs, which allow DETC precursors to mature and expand within the epidermal microenvironment.

Animals↗

PubMed2000

Structure of the human retinoblastoma-related p107 gene and its intragenic deletion in a B-cell lymphoma cell line.

The human p107 protein shares many structural and functional features with the retinoblastoma gene product and retinoblastoma-related p130 protein. In this study, we have cloned and elucidated the complete intron-exon organization of the gene encoding the p107 protein. The gene contains 22 exons spanning over 100kilobase pairs of genomic DNA. The length of individual exons ranges from 50 to 840base pairs. The arrays of exons in the p107 gene are rather similar among members of the gene family, especially to those of the p130 gene, while the length of introns is extensively diverse. This study will provide a molecular basis for implementing comprehensive screening for p107 mutations using genomic DNAs from human malignancies. We also show a detailed structure of an intragenic deletion of the p107 gene found in a human B-cell lymphoma cell line, KAL-1, which was shown to occur by homologous recombination between the two directly repeated Alu family sequences.

Base Sequence↗

PubMed2000

Ineffective control of murine cytomegalovirus by IE1-specific cytotoxic T lymphocytes during protracted infection in the lung.

Interstitial pneumonia caused by cytomegalovirus (CMV) is a fatal disease in immunocompromised patients. In order to examine the defense mechanism against the virus in the lung, we employed an intratracheal infection model in susceptible mice. In mice infected intratracheally with murine CMV, a protracted infection was observed where infectious virus was detected up to 21 days of infection. During this prolonged infection, massive accumulation in the lung of CD8+ T cells with activated phenotypes occurred and these CD8+ T cells showed direct ex vivo cytolytic activity against target cells pulsed with the nonamer peptide derived from IE1 protein of the virus, which has been shown to be the dominant epitope recognized by most of virus-specific CTL. Moreover, adoptive transfer of in vitro induced IE1 peptide-specific CTL line showed no anti-virus effect in the lung, although they were effective in the spleen. Hence, there is reason to assume the IE1-specific CTL induced in vivo or in vitro plays limited roles during the prolonged infection in the lung.

Animals↗

PubMed2000

Characterization of CD4- CD8- CD3+ T-cell receptor-alphabeta+ T cells in murine cytomegalovirus infection.

In this study, we have investigated that after the intraperitoneal infection with murine cytomegalovirus (MCMV), the CD3+ CD4- CD8-(double negative; DN) T-cell receptor (TCR)alphabeta+ T cells increased in peritoneal cavity, liver and spleen in both resistant C57BL/6 and susceptible BALB/c mice. The total cellular population of these cells showed peak levels around day 5 after infection in all the three investigated organs and the following phenotypical and functional characteristics emerged. The peritoneal DN TCRalphabeta+ T cells expressed highly skewed TCRVbeta8 on day 5 after infection compared with the uninfected mice, but those in spleen and liver showed moderate and low skewed TCRVbeta8, respectively. The percentages of NK1.1+ DN TCRalphabeta+ T cells gradually decreased as did modulation of some of their activation markers consistent with an activated cell phenotype. The peritoneal DN TCRalphabeta+ T cells on day 5 after infection expressed the genes of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha, Eta-1 (early T-cell activation-1) and MCP-1 (monocyte chemoattractant protein 1) but lacked expression of interleukin-4 (IL-4). After in vitro stimulation with phorbol 12-myristate 13-acetate and calcium ionophore in the presence of Brefeldin A, higher frequencies of intracellular IFN-gamma+ DN TCRalphabeta+ T cells were detected in all three investigated organs of infected mice compared with those of uninfected mice. Stimulation of peritoneal DN TCRalphabeta+ T cells with plate-bound anti-TCRbeta monoclonal antibodies showed proliferation and also produced IFN-gamma but not IL-4. These results suggest that DN TCRalphabeta+ T cells were activated and may have an antiviral effect through producing IFN-gamma and some macrophage-activating factors during an early phase of MCMV infection.

Animals↗

PubMed2000

Vgamma1+ gammadelta T cells play protective roles at an early phase of murine cytomegalovirus infection through production of interferon-gamma.

Cytomegalovirus (CMV) causes severe opportunistic infection in immunocompromised hosts. The importance of conventional alphabeta T cells in protection against CMV infection has been well documented. However, the role of the second T-cell population (which express the gammadelta T-cell receptor) in CMV infection is not known. In the present study, we analysed the function and protective role of gammadelta T cells in a murine cytomegalovirus (MCMV) infection model. After intraperitoneal infection with MCMV, the number of gammadelta T cells increased in the liver and peritoneal cavity from day 3, and reached a peak on day 5. The gammadelta T cells showed an activated T-cell phenotype and predominantly expressed Vgamma1, which is known to be expressed by heat-shock protein 65 (hsp 65)-specific gammadelta T cells. Analysis of cytokine expression demonstrated that the MCMV-induced gammadelta T cells expressed interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) but not interleukin-4 (IL-4), implying their participation in the cell-mediated immune response against MCMV. Depletion of gammadelta T cells by anti-T-cell receptor (TCR) gammadelta monoclonal antibody (mAb) treatment resulted in significant increase of virus titre and decrease of IFN-gamma in the liver on day 3 after MCMV infection, which further supports the importance of gammadelta T cells in early protection against infection. Finally, the MCMV-induced gammadelta T cells produced IFN-gamma in vitro in response to hsp 65. Our results suggest that gammadelta T cells participate in early protection against MCMV infection through recognition of hsp 65 and production of IFN-gamma.

Animals↗

PubMed1999

Decreases in Ikaros activity correlate with blast crisis in patients with chronic myelogenous leukemia.

Gene targeting studies in mice have shown that the lack of Ikaros activity leads to T-cell hyperproliferation and T-cell neoplasia, establishing the Ikaros gene as a tumor suppressor gene in mice. This prompted us to investigate whether mutations in Ikaros play a role in human hematological malignancies. Reverse transcription-PCR was used to determine the relative expression levels of Ikaros isoforms in a panel of human leukemia/lymphoma cell lines and human bone marrow samples from patients with hematological malignancies. Among the cell lines examined, only BV-173, which was derived from a chronic myelogenous leukemia (CML) patient in lymphoid blast crisis, overexpressed the dominant-negative isoform, Ik-6. In 9 of 17 samples of patients in blast crisis of CML, Ikaros activity had been reduced either by drastically reducing mRNA expression (4 of 17) or by overexpressing the dominant-negative isoform Ik-6 (5 of 17). Significantly, expression of Ikaros isoforms seemed normal in chronic phase CML patients and patients with other hematological malignancies. In some cases, overexpression of the dominant-negative Ik-6 protein was confirmed by Western blot analysis, and Southern blot analysis indicated that decreases in Ikaros activity correlated with a mutation in the Ikaros locus. In summary, these findings suggest that a reduction of Ikaros activity may be an important step in the development of blast crisis in CML and provide further evidence that mutations that alter Ikaros expression may contribute to human hematological malignancies.

Adult↗

PubMed1999

Genetic evidence for functional redundancy of Platelet/Endothelial cell adhesion molecule-1 (PECAM-1): CD31-deficient mice reveal PECAM-1-dependent and PECAM-1-independent functions.

Platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31), a member of the Ig superfamily, is expressed strongly at endothelial cell-cell junctions, on platelets, and on most leukocytes. CD31 has been postulated to play a role in vasculogenesis and angiogenesis, and has been implicated as a key mediator of the transendothelial migration of leukocytes. To further define the physiologic role of CD31, we used targeted gene disruption of the CD31 gene in embryonic stem cells to generate CD31-deficient mice. CD31-deficient mice (CD31KO) are viable and born at the expected Mendelian frequency, remain healthy, and exhibit no obvious vascular developmental defects. In response to inflammatory challenge, polymorphonuclear leukocytes of CD31KO mice are arrested between the vascular endothelium and the basement membrane of inflammatory site mesenteric microvessels, confirming a role for CD31 in the migration of neutrophils through the subendothelial extracellular matrix. Normal numbers of leukocytes are recovered from inflammatory sites in CD31KO mice, however, suggesting that the defect in leukocyte migration across basal lamina observed in the absence of CD31 may be compensated for by the use of other adhesion molecules, or possibly an increased rate of migration. Homing of T lymphocytes in vivo is normal, and CD31KO mice are able to mount a cutaneous hypersensitivity response normally. In addition, CD31-mediated homophilic adhesion does not appear to play a role in platelet aggregation in vitro. This study provides genetic evidence that CD31 is involved in transbasement membrane migration, but does not play an obligatory role in either vascular development or leukocyte migration.

Animals↗

PubMed1999

Protective effects of hochu-ekki-to, a Chinese traditional herbal medicine against murine cytomegalovirus infection.

The innate immunity against murine cytomegalovirus (MCMV) at the early phase of infection is mediated by NK cells and macrophages. We studied the effects of hochu-ekki-to (HET), a traditional Chinese herbal medicine, on the regulation of innate immunity mediated by NK cells and macrophages. We found the oral administration of HET to increase both the number of leukocytes in the spleen and liver and the splenic NK cell cytotoxicity associated with the increased induction of serum IFN-alpha/beta after an MCMV infection but it had no effect on liver NK cells. However, no differences were found in the serum IL-12, IFN-gamma, TNF-alpha and nitric oxide (NO) production in the culture of macrophages between the HET- and PBS-treated mice on day 2 after MCMV infection. In addition, HET-treated splenic and peritoneal macrophages were found to show a higher intrinsic resistance against in vitro MCMV infection than that of PBS-treated mice. Therefore, the HET-induced effects on NK cells and macrophages selectively reduced the viral load in the spleen but not in the liver at an early phase of MCMV infection. HET may thus be useful in the treatment of human cytomegalovirus infection which commonly occurs in HIV-infected AIDS patients.

3T3 Cells↗

PubMed1999

Accelerated recovery from cyclophosphamide-induced leukopenia in mice administered a Japanese ethical herbal drug, Hochu-ekki-to.

The effect of a Japanese ethical herbal drug, Hochu-ekki-to (HOT), on recovery from leukopenia induced by cyclophosphamide (CY) was investigated. Daily oral administration of 1000 mg/kg HOT into CY-treated mice significantly prevented decrease of leukocyte numbers in the peripheral blood and accelerated recovery from leukopenia. Ginsenoside Rgl extracted from Ginseng radix, a major herb of HOT, was one of the active ingredients. HOT increased numbers of neutrophils and monocytes in the peripheral blood compared with CY-treated control. Moreover, HOT augmented the resistance against Pseudomonas aeruginosa infection. The number of colony-forming units in the spleen (CFU-S) also increased in HOT-treated mice. The frequencies of IL-3-, GM-CSF- and IFN-gamma-producing cells increased in the spleen, bone marrow, liver and IEL on HOT treatment, and HOT clearly augmented the expressions of IL-3, GM-CSF and IFN-gamma mRNA in the spleen, bone marrow, liver and IEL except IL-3 and IFN-gamma mRNA in the IEL. These results suggest that HOT enhances the production of hematopoietic lymphokines, stimulates the proliferation of hematopoietic progenitor cells and consequently accelerates recovery from leukopenia in CY-treated mice. Additionally, IFN-gamma which HOT-augmented the production may contribute the protective effect against the bacterial infection by activating of phagocyte cells.

Animals↗