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Biomedical subjects

K Itoh

Publications and source records attributed to K Itoh.

At least 217 records · Page 12Linked to original sources
PubMed2000

Quenching of a photosensitized dye through single-electron transfer from trivalent phosphorus compounds

Various types of trivalent phosphorus compounds 1 undergo single-electron transfer (SET) to the photoexcited state of rhodamine 6G (Rho+*) in aqueous acetonitrile to quench the fluorescence from Rho+*. The rate constants kp for the overall SET process were determined by the Stern-Volmer method. The rate is nearly constant at a diffusion-controlled limit in the region of E1/2(1) < 1.3 V (vs Ag/Ag+), whereas log kp depends linearly on E1/2(1) in the region of E1/2(1) > 1.3 V, the slope of the correlation line being -alphaF/RT with alpha = 0.2. The potential at which the change in dependence of log kp on E1/2(1) occurs (1.3 V) is in accordance with the value of E1/2(Rho+*) (1.22 V) that has been obtained experimentally. Thus, the SET step is exothermic when E1/2(1) < 1.3 V and endothermic when E1/2(1) > 1.3 V. The alpha-value (0.2) obtained in the endothermic region shows that the SET step from 1 to Rho+* is irreversible in this region. Trivalent phosphorus radical cation 1*+ generated in the SET step undergoes an ionic reaction with water in the solvent rapidly enough to make the SET step irreversible. In contrast, the SET from amines 2 and alkoxybenzenes 3 to Rho+* is reversible when the SET step is endothermic, meaning that the radical cations 2*+ and 3*+ generated in the SET step undergo rapid "back SET" in the ground state to regenerate 2 and 3.

Journal Article↗
PubMed2000

Induction of tryptophan 2,3-dioxygenase in the mouse endometrium during implantation.

Indoleamine 2,3-dioxygenase (IDO) is expressed in trophoblasts and defends the conceptus against rejection by reducing the tryptophan level and suppressing the T cell activity. We isolated a cDNA for tryptophan 2,3-dioxygenase (TDO), another key catabolizing enzyme of tryptophan, from a mouse uterus cDNA library enriched with pregnancy-induced genes. Northern blot and in situ hybridization analyses demonstrated that the TDO mRNA was induced in the decidualized stromal cells around the implanted embryo at the time of implantation. The expression was then upregulated and primarily localized at the mesometrial decidua. TDO mRNA was induced by deciduoma formation as well as embryo transfer but not by ovarian steroid hormones. These findings demonstrated that TDO is induced in the endometrial stromal cells concomitant with decidualization and suggested its involvement in the implantation process by regulating the tryptophan level at the implantation site.

Animals↗
PubMed2000

Identification of a new endoplasmic reticulum-resident protein recognized by HLA-A24-restricted tumor-infiltrating lymphocytes of lung cancer.

To help clarify the molecular basis of tumor immunology in lung cancer, we have investigated antigens recognized by HLA-A24-restricted CTLs established from T cells infiltrating into lung adenocarcinoma and report a new gene encoding tumor epitopes recognized by the CTLs. This gene was located on chromosome 4q31.22 and encoded an unreported endoplasmic reticulum-resident protein with 412 deduced amino acids. This protein had a molecular mass of 46 kDa and was expressed in the majority of malignant cells and tissues tested, with the exception of T-cell leukemia cells, but was not expressed in a panel of normal cells and tissues, except in those of the testis, placenta, and fetal liver. Two peptides at positions 13-20 and 75-84 were recognized by the CTLs and had an ability to induce HLA-A24-restricted and tumor-specific CTLs in peripheral blood mononuclear cells of lung cancer patients. Thus, these peptides might be appropriate molecules for use in the specific immunotherapy of HLA-A24+ patients with lung and other cancers.

Adenocarcinoma↗
PubMed2000

Differential expression of alternatively spliced neural cell adhesion molecule L1 isoforms during oligodendrocyte maturation.

The expression of neural cell adhesion molecules and myelin-specific molecules is precisely regulated according to cell type and developmental age. We investigated whether different isoforms of these molecules change during development of oligodendrocytes. Immature oligodendrocytes cultured from embryonic day 18 rat cerebrum were distinguished into early stage and late stage by morphological and immunocytochemical criteria. mRNA levels of the neural cell adhesion molecule L1 in late-stage immature oligodendrocytes were approximately fivefold higher than in early-stage cells, but early-stage immature oligodendrocytes predominantly expressed an L1 spliced isoform lacking two region (exon 2 and 27). Late-stage cells expressed full-length L1 identical to the neuronal form. mRNA for the neural cell adhesion molecules NCAM and MAG did not show any difference in expression pattern. These results suggest that alternatively spliced isoforms of L1 might be regulated by temporal and spatial factors during oligodendrocyte development.

Age Factors↗
PubMed2000

Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages.

Electrophiles and reactive oxygen species have been implicated in the pathogenesis of many diseases. Transcription factor Nrf2 was recently identified as a general regulator of one defense mechanism against such havoc. Nrf2 regulates the inducible expression of a group of detoxication enzymes, such as glutathione S-transferase and NAD(P)H:quinone oxidoreductase, via antioxidant response elements. Using peritoneal macrophages from Nrf2-deficient mice, we show here that Nrf2 also controls the expression of a group of electrophile- and oxidative stress-inducible proteins and activities, which includes heme oxygenase-1, A170, peroxiredoxin MSP23, and cystine membrane transport (system x(c)(-)) activity. The response to electrophilic and reactive oxygen species-producing agents was profoundly impaired in Nrf2-deficient cells. The lack of induction of system x(c)(-) activity resulted in the minimum level of intracellular glutathione, and Nrf2-deficient cells were more sensitive to toxic electrophiles. Several stress agents induced the DNA binding activity of Nrf2 in the nucleus without increasing its mRNA level. Thus Nrf2 regulates a wide-ranging metabolic response to oxidative stress.

Adaptor Proteins, Signal Transducing↗
PubMed2000

SDH activity and cell size of tibialis anterior motoneurons and muscle fibers in SAMP6.

Succinate dehydrogenase (SDH) activities and cross-sectional areas (CSAs) of tibialis anterior motoneurons and muscle fibers were determined in 20-, 40-, and 60-week-old male senescence-accelerated mice (SAMP6), and compared with those in age-matched accelerated-senescence resistant mice (SAMR1). The mean CSA of motoneurons in SAMP6 decreased at 60 weeks, primarily due to a selective loss of large (>400 microm2) motoneurons. The mean SDH activity of motoneurons with CSAs between 100 and 400 microm2 decreased in SAMP6, but not SAMR1, at 60 weeks. The mean muscle fiber SDH activities and CSAs in SAMP6 decreased at 60 weeks. There were no differences in the mean SDH activity or CSA of motoneurons or muscle fibers among 20-, 40-, and 60-week-old SAMR1. These results demonstrate that mice which have been shown to have a variety of accelerated-senescent features also have an earlier onset of age-related changes in motoneurons and the muscle fibers that they innervate when compared with age-matched accelerated-senescence resistant mice.

Age Factors↗
PubMed2000

Identification of a gene coding for a new squamous cell carcinoma antigen recognized by the CTL.

Peptide-based specific immunotherapy has resulted in tumor regression in some melanoma patients. However, tumor Ags and peptides for specific immunotherapy, except for treatment of melanomas, have not yet been well identified. In this study, we report a gene encoding a new squamous cell carcinoma (SCC) Ag recognized by cells of the HLA-A24-restricted and tumor-specific CTL line. This gene with 3958-bp length was transcribed from the chromosome 6q22 with six exons, and its mRNA was ubiquitously expressed in both SCCs and normal tissues, and partly expressed in adenocarcinomas. The deduced 958-aa sequence encoded by this gene showed no similarity to any known amino acid sequences. This gene product had a characteristic of an endoplasmic reticulum-resident protein. A 100-kDa protein was detected in the vast majority of SCCs from various tissues, in majority of renal cell carcinomas and brain tumors, and in about one-third of melanomas and adenocarcinomas from various organs other than the breast. In contrast, it was not expressed at all in any of the normal cells or tissues tested, including the testis and fetal liver. Three different peptides at positions 93-101, 161-169, and 899-907 of this Ag were recognized by this CTL line, and all of them induced HLA-A24-restricted and tumor-specific CTLs from PBMCs of SCC patients. Therefore, these peptides may be useful for peptide-based specific immunotherapy of HLA-A24+ patients with SCC in various organs, as well as for treatment of other cancer.

Amino Acid Sequence↗
PubMed2000

High-pressure synthesis of the polymorph of layer structured compounds MNX (M = Zr, Hf; X = Cl, Br, I).

Transition metal nitride halides MNX (M = Zr, Hf; X = Cl, Br, I) have two types of layer structured polymorphs, the alpha-form with the FeOCl type and the beta-form with the SmSI type. Both polymorphs consist of corrugated double M-N layers sandwiched between halogen layers, but with different atomic arrangements within the layers. The beta-form had been considered to be a high-temperature polymorph, because some beta-forms were obtained by thermal treatment of the corresponding alpha-forms. Here, the alpha-form was successfully transformed into the beta-form under high-pressure and high-temperature conditions; the new members of the beta-form were prepared for the first time from alpha-HfNBr, alpha-ZrNI, and alpha-HfNI using a high pressure of 3-5 GPa at 900 degrees C. The beta-form should be characterized as the high-pressure form rather than the corresponding high-temperature polymorph. This is the first high-pressure study on the polymorphs of metal nitride systems.

Journal Article↗
PubMed2000

Target cells of apoptosis in the adult murine dentate gyrus and O4 immunoreactivity after ionizing radiation.

The occurrence of radiation-induced apoptosis and the determination of target cells were investigated by using the TdT-mediated dUTP-biotin nick end labeling assay and immunohistochemical analyses. The O4 immunoreactivity, an oligodendrocytes surface antigen, was also evaluated by using western blotting analysis. C57BL/6J adult female mice were subjected to single dose irradiation of 10 Gy. Eight hours after irradiation, the most significant increase of apoptotic cells was detected in the subgranular zone and the hilus of the dentate gyrus. The target cells of radiation-induced apoptosis are the subgranular progenitor cells and the oligodendrocytes in the hilus. The amount of the O4 immunoreactivity, a marker for premature oligodendrocytes, was unchanged until 8 h but enhanced after 12 h of irradiation. These results are the first to show the increase of the O4 immunoreactivity after irradiation and may be associated with the pathogenesis of radiation injury.

Animals↗
PubMed2000

Retroviral vector-mediated gene expression in human CD34+CD38- cells expanded in vitro: cis elements of FMEV are superior to those of Mo-MuLV.

A novel murine stromal cell line, HESS-M28, was established, which supports the expansion of human CD34+CD38- cells more than 300-fold in vitro in the presence of human IL-3 and SCF. These cells were used in an attempt to evaluate cis-acting elements of retroviral vectors in human primitive hematopoietic cells. Cord blood cells were cultured on top of the mixed cell layers of the stromal cell line, HESS-M28, and retroviral vector-producing cells. The FMEV-type vector SF/Lyt contained the spleen focus-forming virus U3 and the MESV primer-binding site (PBS), while MO3/Lyt contained the U3 region and PBS from Mo-MuLV. After transduction by the FMEV-type and Mo-MuLV-based vectors, expression of the marker gene murine CD8 (mCD8) was examined in CD34-, CD34+, and CD34+CD38- cells. In CD34+ and CD34+CD38- cells, expression of mCD8 was higher with the FMEV-type vector, SF/Lyt, compared with the cells transduced by the Mo-MuLV-based vector MO3/Lyt, although the expression was comparable in CD34- cells. Expression of marker genes was also confirmed in long-term culture-initiating cells (LTC-ICs) and SCID-repopulating cells (SRCs).

ADP-ribosyl Cyclase↗
PubMed2000

Serum MAGE-4 protein in ovarian cancer patients.

OBJECTIVE: We measured serum levels of MAGE-4 protein in patients with ovarian cancer to investigate the relationship between serum MAGE-4 positivity and prognosis. METHODS: Serum levels of MAGE-4 protein were measured with an ELISA system. RESULTS: Serum levels of MAGE-4 in patients with ovarian cancer were significantly higher than levels in patients with benign diseases. Serum MAGE-4 protein was considered positive in 22% of primary ovarian cancer patients. The positive rate was the highest in sera of patients with surface epithelial-stromal tumors, particularly serous adenocarcinomas (24%). The survival time after a primary surgical operation in ovarian cancer patients with serum MAGE-4 positivity was significantly shorter than that of MAGE-4-negative cases. CONCLUSION: These results suggest that serum MAGE-4 protein is a potential prognostic factor of reduced survival in ovarian cancer patients.

Adult↗
PubMed2000

Passive and active recognition of one's own face.

Facial identity recognition has been studied mainly with explicit discrimination requirement and faces of social figures in previous human brain imaging studies. We performed a PET activation study with normal volunteers in facial identity recognition tasks using the subject's own face as visual stimulus. Three tasks were designed so that the activation of the visual representation of the face and the effect of sustained attention to the representation could be separately examined: a control-face recognition task (C), a passive own-face recognition task (no explicit discrimination was required) (P), and an active own-face recognition task (explicit discrimination was required) (A). Increased skin conductance responses during recognition of own face were seen in both task P and task A, suggesting the occurrence of psychophysiological changes during recognition of one's own face. The left fusiform gyrus, the right supramarginal gyrus, the left putamen, and the right hypothalamus were activated in tasks P and A compared with task C. The left fusiform gyrus and the right supramarginal gyrus are considered to be involved in the representation of one's own face. The activation in the right supramarginal gyrus may be associated with the representation of one's own face as a part of one's own body. The prefrontal cortices, the right anterior cingulate, the right presupplementary motor area, and the left insula were specifically activated during task A compared with tasks C and P, indicating that these regions may be involved in the sustained attention to the representation of one's own face.

Adult↗
PubMed2000

Expression of the SART1 tumor-rejection antigens in colorectal cancers.

PURPOSE: Colorectal cancer is one of the major causes of cancer death in the world, including in the United States and Japan. We recently identified the tumor-rejection antigen gene SART1, which encodes both the SART1(259) antigen expressed in the cytosol of epithelial cancers and the SART1(800) antigen expressed in the nucleus of the majority of proliferating cells. This study investigated the expression of these tumor antigens to explore a potential molecule for specific immunotherapy of colorectal cancer patients. METHODS: SART1 antigens were investigated by Western blotting in six colorectal cancer cell lines and in 33 colorectal cancer tissues. The cancer cell lines were tested for their ability to stimulate interferon-gamma production by the human-leukocyte-antigen-A24-restricted and SART1-specific cytotoxic T lymphocytes and were also tested for their susceptibility to the lysis by the cytotoxic T lymphocytes. RESULTS: The SART1(259) antigen was detected in the cytosol of four of six cancer cell lines, 13 of 33 (39 percent) cancer tissues, and 0 of 20 nontumorous colorectal tissues. The SART1(800) antigen was expressed in the nucleus of all the colorectal cancer cell lines, 18 of 33 (55 percent) cancer tissues, and 0 of 20 nontumorous tissues. The human-lymphocyte-antigen-A24-restricted and SART1-specific cytotoxic T lymphocytes killed the human-lymphocyte-antigen-A24+ SART1(259+) cancer cells. CONCLUSIONS: The SART1(259) antigen could be an appropriate target molecule for specific immunotherapy of approximately 40 percent of the human-lymphocyte-antigen-A24+ patients with colorectal cancer.

Adenocarcinoma↗
PubMed2000

Readministration of tamoxifen after adjuvant therapy for recurrent breast cancer.

BACKGROUND: Previous series concerning tamoxifen (TAM) rechallenge did not obtain satisfactory results. Using stricter criteria, we now assess the usefulness of readministration of TAM as an initial therapy for patients with recurrent breast cancer. METHOD: The eligibility criteria were postmenopausal, estrogen receptor (ER) positive or unknown, at least 12 months of adjuvant TAM, a 6-month or longer drug-free period and no previous therapy after recurrence. A total of 10 patients were enrolled. TAM was administered in daily doses of 20 or 30 mg. RESULTS: The mean age of the patients at the time of recurrence was 64.8 years. The receptor status was positive in 8 patients and unknown in 2. The median disease-free interval (DFI) after mastectomy was 71.7 months. A complete response was observed in one patient, a partial response in 6, stable disease in 2, and progression in one. The response rate was thus 70%, with an additional two patients showing no progression over 6 months. Although only one patient with a DFI of less than 48 months showed a positive response, all patients with a DFI longer than 48 months showed a clinical response. The duration of response was less than 12 months in 3 patients and longer in 4. CONCLUSION: The post-adjuvant readministration of tamoxifen is a useful first choice therapy for postmenopausal recurrent breast cancer patients with positive ER and longer DFI.

Aged↗
PubMed2000

Reappraisal of single-sample and gamma camera methods for determination of the glomerular filtration rate with 99mTc-DTPA.

The aim of this study was to assess the clinical validity of single-sample methods and gamma camera uptake methods with 99mTc-DTPA for the estimation of the glomerular filtration rate (GFR). The study was performed in 50 patients with various degrees of renal function (29 males and 21 females; age 27-90 yrs; serum creatinine level 0.34-6.49 mg/dl). As a reference the "true" GFR (GFRt) was determined from plasma clearance by means of the two compartment model curve fitting 10 plasma samples. The GFRt of more than 30 ml/min in 46 patients was compared to the GFR which was estimated with 7 single-sample methods, two gamma camera uptake methods and 24-hour endogenous creatinine clearance (24hCcr). Close correlation was observed in all single-sample methods. The highest linear correlation was observed in the Christensen and Groth's method rewritten by Watson for a 180-min plasma sample (r = 0.991, see = 5.84 ml/min). The smallest random error was observed in the Groth and Aasted's method for a 180-min plasma (r = 0.989, see = 4.31 ml/min/1.73 m2). Our method was lowest in % absolute difference analysis (mean = 4.10%). The gamma camera uptake methods correlated significantly with the GFRt (r = 0.746-0.774), but were less reliable than any of the single-sample methods (see = 15.41 ml/min-19.14 ml/min). The lowest correlation was observed in the 24hCcr (r = 0.698, see = 50.76 ml/min/1.73 m2). The single-sample method was more accurate than the gamma camera method, and the gamma camera method was more accurate than 24hCcr. The single-sample method should be recommended for the accurate determination of the GFR with 99mTc-DTPA in a patient with mild to moderate renal dysfunction.

Adult↗
PubMed2000

Oblique plication for repair of the atrialized ventricle and tricuspid incompetence of Ebstein's anomaly.

An 8-year-old girl who weighed 42 kg presented Ebstein's anomaly with severe tricuspid incompetence, and mild systemic cyanosis during exercise. A new reconstructive procedure for this complex anomaly was used. Oblique transference of the displaced posterior leaflet was performed, which resulted in plication of the atrialized ventricle and reduction in the tricuspid annular diameter. This procedure requires neither detachment nor closure of the tricuspid valve.

Child↗