Biomedical subjects

T Inaba

Publications and source records attributed to T Inaba.

At least 109 records · Page 6Linked to original sources

PubMed1999

Identification of a cis-regulatory element involved in phytochrome down-regulated expression of the pea small GTPase gene pra2.

The pra2 gene encodes a pea (Pisum sativum) small GTPase belonging to the YPT/rab family, and its expression is down-regulated by light, mediated by phytochrome. We have isolated and characterized a genomic clone of this gene and constructed a fusion DNA of its 5'-upstream region in front of the gene for firefly luciferase. Using this construct in a transient assay, we determined a pra2 cis-regulatory region sufficient to direct the light down-regulation of the luciferase reporter gene. Both 5'- and internal deletion analyses revealed that the 93-bp sequence between -734 and -642 from the transcriptional start site was important for phytochrome down-regulation. Gain-of-function analysis showed that this 93-bp region could confer light down-regulation when fused to the cauliflower mosaic virus 35S promoter. Furthermore, linker-scanning analysis showed that a 12-bp sequence within the 93-bp region mediated phytochrome down-regulation. Gel-retardation analysis showed the presence of a nuclear factor that was specifically bound to the 12-bp sequence in vitro. These results indicate that this element is a cis-regulatory element involved in phytochrome down-regulated expression.

Amino Acid Sequence↗

PubMed1999

B-cell lymphoma associated with haemophagocytic syndrome: a clinical, immunological and cytogenetic study.

B-cell lymphoma associated with haemophagocytic syndrome (HPS) is extremely rare in Western countries but has recently been increasingly reported in Asian countries. We describe seven patients with B-cell lymphoma associated with HPS, six males and one female, age range 41-82 years (median 63 years). All patients had fever and splenomegaly, and six of the seven patients had hepatomegaly with no associated lymphadenopathy. The bone marrow showed haemophagocytosis and an infiltration of lymphoma cells. All patients showed increased levels of lactate dehydrogenase, C-reactive protein, ferritin and soluble interleukin-2 receptor. Lymphoma cells were positive for CD19. CD20 and surface immunoglobulin in all patients examined, and positive for CD5 in four of seven patients. Cytogenetic analyses of bone marrow cells showed a complex structural abnormality including chromosome 14q32 in two patients, 19q13 in three patients and deletion of the terminal part of 8p21 in six patients. The prognosis was poor; only two of the seven patients have survived in complete remission with a median survival of 11 months. These data suggested that B-cell lymphoma associated with HPS might constitute a distinct biological and clinical disease entity. Abnormality of chromosome 19q13 and loss of 8p21 might be involved in the pathogenesis of this disease.

Adult↗

PubMed1999

Two distinct interleukin-3-mediated signal pathways, Ras-NFIL3 (E4BP4) and Bcl-xL, regulate the survival of murine pro-B lymphocytes.

Hematopoietic cells require cytokine-initiated signals for survival as well as proliferation. The pathways that transduce these signals, ensuring timely regulation of cell fate genes, remain largely undefined. The NFIL3 (E4BP4) transcription factor, Bcl-xL, and constitutively active mutants of components in Ras signal transduction pathways have been identified as key regulation proteins affecting murine interleukin-3 (IL-3)-dependent cell survival. Here we show that expression of NFIL3 is regulated by oncogenic Ras mutants through both the Raf-mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways. NFIL3 inhibits apoptosis without affecting Bcl-xL expression. By contrast, Bcl-xL levels are regulated through the membrane proximal portion in the cytoplasmic domain of the receptor (betac chain), which is shared by IL-3 and granulocyte-macrophage colony-stimulating factor. Activation of either pathway alone is insufficient to ensure cell survival, indicating that multiple independent signal transduction pathways mediate the survival of developing B-lymphoid cells.

Animals↗

PubMed1999

Parasitological survey on wild carnivora in north-western Tohoku, Japan.

In the winter of 1997-1998, we collected parasitological data from 60 wild carnivora in the north-western part of Tohoku region, Japan. These included 7 foxes (Vulpes vulpes japonica), 20 raccoon dogs (Nyctereutes procyonoides viverrinus), 29 martens (Martes melampus melampus), 3 weasels (two Mustela sibirica itatsi and one M. nivalis namiyei), and one Japanese badger (Meles meles anakuma). Roundworms (Toxocara canis in foxes and Toxocara tanuki in raccoon dogs), hookworms (Ancylostoma kusimaense and Arthrostoma miyazakiense) and Molineus sp. in the small intestine were the most prevalent in foxes and raccoon dogs. In martens, Aonchotheca putorii in the stomach, Concinnum ten in the pancreatic duct, Molineus sp. and Euryhelmis costaricensis in the small intestine were the most prevalent. Collected parasites include some new helminth species for this region or Japan; the strobilar stage of Taenia polyacantha from foxes, Pygidliopsis summa from a raccoon dog, Eucoleus aerophilus, A. putorii, and Soholiphyme baturini from martens.

Animals↗

PubMed1999

Helminth fauna of carnivores distributed in north-western Tohoku, Japan, with special reference to Mesocestoides paucitesticulus and Brachylaima tokudai.

In the winter of 1998-1999, we collected parasitological data from 54 wild carnivores in the north-western part of Tohoku region, Japan. These consisted of 38 martens (Martes melampus melampus), 14 raccoon dogs (Nyctereutes procyonoides viverrinus) and 2 foxes (Vulpes vulpes japonica). Collected helminth parasites were 11 nematode, 10 trematode, 3 cestode, and a single acanthocephalan species, including 5 hitherto unknown species for this research area or the mainland of Japan (Honshu). Mesocestoides paucitesticulus was for the first time recorded from martens as well as from carnivores distributed in Honshu. Brachylaima tokudai originally recorded from Urotrichus talpoides in the central part of Honshu was for the first time found from a raccoon dog.

Acanthocephala↗

PubMed1999

Clinical characteristics of amiodarone-induced thyrotoxicosis and hypothyroidism in Japan.

Since amiodarone was introduced in Japan in 1992, the incidence of the drug-induced thyroid dysfunction has been increasing. We studied the thyroid function of 13 patients with amiodarone-induced thyrotoxicosis (AIT) and 11 patients with amiodarone-associated hypothyroidism (AAH) who had been referred to our Institute in the last 6 years. AIT and AAH developed after 39+/-21 and 20+/-16 months of amiodarone treatment, respectively. One patient developed AAH followed by AIT. The AIT ranged from subclinical to overt thyrotoxicosis. Four patients with moderate to marked AIT were treated with methimazole. Their thyrotoxicosis persisted for 3 to 9 months, despite administration of antithyroid agents. One patient with mild thyrotoxicosis was treated with prednisolone, resulting in a euthyroid state in a few months. Eight patients with asymptomatic to moderate thyrotoxicosis resolved spontaneously without any treatment. In four asymptomatic patients with AIT, serum levels of T3 and T4 were in the upper normal range or slightly high (< 12 microg/dl), accompanied by suppressed TSH (<0.1 microU/ml) and high thyroglobulin levels, suggesting destruction-induced thyrotoxicosis. Such a subclinical thyrotoxicosis developed repeatedly in one patient. Ultrasonographic studies revealed no nodular lesion in the thyroid, and color flow Doppler sonography demonstrated no hypervascularity in the thyroid gland in any AIT patient. Although it is postulated in Europe that there are two types of AIT, namely type I, which develops in patients with latent Graves' disease or toxic multinodular goiter, and type II, which develops in an apparently normal thyroid as destructive thyroiditis, all AIT patients we have seen so far had developed destructive type AIT. Sufficient intake of iodide and a very low incidence of toxic multinodular goiter may account for the rare incidence of type I AIT in our country. Mild to moderate AIT resolved spontaneously without discontinuing amiodarone, but it was discontinued in two of 13 AIT patients because of extrathyroidal adverse reactions.

Adult↗

PubMed1999

[Discrimination of leukoencephalopathy from leukemic cell invasion by MR spectroscopy in a patient with acute lymphoblastic leukemia].

A 58-year-old man was admitted to our hospital in November 1992 because of fever and arthralgia. He was given a diagnosis of acute lymphoblastic leukemia and treated with an Ad-VP regimen, which resulted in complete remission. After two courses of consolidation therapy and intrathecal (IT) injections of methotrexate, Ara-C, and prednisolone the patient received high-dose Ara-C plus VP-16 followed by recombinant human G-CSF for the collection of peripheral blood stem cells. However, he relapsed with the appearance of leukemic cells in cerebrospinal fluid (CSF), and was accordingly given IT injections 8 more times. After the disappearance of leukemic cells from CSF, the patient received a peripheral blood stem cell transplant (PBSCT) and achieved rapid hematopoietic recovery. However, he suffered mental aberrations and loss of consciousness 9 days after PBSCT. Proton magnetic resonance spectroscopy (1H-MRS) disclosed severe necrosis due to leukoencephalopathy in the frontal lobe and invasion of leukemic cells around the lateral ventricles. The patient did not receive any therapy for neurological symptoms because of severe necrosis in the frontal lobe, and died of bone marrow relapse in April 1995. MRS is useful for the discrimination of leukoencephalopathy from leukemic cell invasion.

Antineoplastic Agents↗

PubMed1999

Comparative evolutionary pharmacogenetics of CYP2D6 in Ngawbe and Embera Amerindians of Panama and Colombia: role of selection versus drift in world populations.

The development of CYP2D6 has been attributed to the need of earth-dwelling animals to detoxify toxic xenobiotics (phytoalexins) present in plants. This hypothesis has been extrapolated to humans, but is yet unconfirmed. Therefore, we studied two Amerindian populations as the best available model to test the effect of selection through diet on human CYP2D6 evolution. The frequency of sparteine poor metabolizers in Ngawbe was 4.4% (n = 344), while the frequency in Embera was 2.2% (n = 153). Among Ngawbe and Embera, CYP2D6*4 (allelic frequencies for each tribe, respectively: 0.171; 0.14), CYP2D6*6 (0.005; 0.011) and CYP2D6*10 (0.175; 0.069) were detected, while CYP2D6*3, CYP2D6*5, CYP2D6*9 and CYP2D6*16 were absent. All poor metabolizers possessed either CYP2D6*4 or CYP2D6*6 and there were no disagreements between genotypic and phenotypic data. The total frequency of mutant alleles showed no difference among Amerindians or when compared to Caucasians. It was higher than in Chinese, since the frequency of CYP2D6*4 was higher in Amerindians. XbaI restriction fragment length polymorphisms haplotypes were very homogeneous in Amerindians, because the only fragment that hybridized with the CYP2D6 cDNA probe was the 29 kb (not 42/44 kb or 11.5/13 kb). This indicated no gene cluster recombinations that generate insertions or deletions. We propose that in earlier hominids and humans, CYP2D6 had increasingly become a vestigial characteristic unconstrained by dietary stressors, as a result of cultural survival strategies. Human CYP2D6 evolution was preferentially affected by random genetic drift, and not by adaptive or purifying selection.

Colombia↗

PubMed1999

[Therapeutic efficacy of intra-peritoneal infusion of cisplatin and continuous intravenous infusion of 5-fluorouracil in gastric cancer patients with peritoneal metastasis].

A combination chemotherapy with intra-peritoneal infusion of CDDP and continuous intravenous infusion of 5-FU was used with a total of 16 gastric cancer patients with peritoneal metastasis (P 2 or P 3). Infuse A-port was inserted at the time of operation, CDDP 70 mg/m2 was administered intra-peritoneally at day 1, and 5-FU 700 mg/m2 was continuously administered intravenously at day 1-5. This treatment was repeated twice. Toxicity was evaluated according to the criteria from JCOG. Major toxicities of this regimen were anemia, leukocytopenia and nausea/vomiting. Except for one patient with Grade 3 venous thrombosis, all toxicities were less than Grade 2 and well tolerable. Median survival time was 343 days, but, one patient has survived more than 6 years. According to the multivariate analyses, depth of invasion was selected as an independent prognostic factor for this treatment. This therapy is considered to be a safe and effective treatment modality for gastric cancer patients with peritoneal metastasis.

Adult↗

PubMed1999

Occurrence of myocarditis in rodents infected with Schistosoma mansoni.

Myocarditis is a complication of Schistosoma mansoni infection, although the literature does not provide much information regarding the frequency of myocarditis. In order to analyze the relationship between myocarditis and S. mansoni infection, different laboratory animals were infected with different dose of cercariae. At different weeks of post infection the hearts of infected animals were collected and processed for histopathological examination. Myocarditis was characterized by interstitial inflammatory cell infiltration with or without granuloma. ddY and ICR infected mice showed eosinophilic egg-granuloma in the heart where as neither eosinophil nor egg-granuloma were observed in the heart of infected gerbils. Higher number of eosinophils and greater size of the granuloma were found in the ddY mice than ICR mice. The number of eosinophils was significantly higher in severe myocarditis. Incidence of myocarditis was higher in ddY mice (69% with 100) than ICR mice (35%) and gerbils (23%). The results indicate that ddY mice were more susceptible to S. mansoni infection in the development of myocarditis and myocardial severity was associated with greater eosinophil infiltration. These findings suggest that eosinophils might be involved in the development of myocarditis, although the involvement of immunological reaction can not be ruled out.

Animals↗

PubMed1998

Successful transfer of ADA gene in vitro into human peripheral blood CD34+ cells by transfecting EBV-based episomal vectors.

We report a novel non-viral system for transfecting human immature hematopoietic cells in vitro. Epstein-Barr virus (EBV)-based episomal vectors carrying human adenosine deaminase (ADA) gene cDNA were transfected by electroporation into human peripheral blood (PB) CD34+ cells. The transgene-specific mRNA were detected from 37 to 100% of CFU-c (colony forming unit in culture) colonies derived from the transfected cells. A two-fold increase in enzyme activity was also found. These results indicate the successful transfer and expression of genes in human immature hematopoietic cells using the EBV-based episomal vector system.

Adenosine Deaminase↗

PubMed1998

Transcription factor NF-E2 is essential for the polyploidization of a human megakaryoblastic cell line, Meg-J.

Transcription factors regulating the process of megakaryocyte development remain largely unclarified. To clarify them further, we used a human megakaryoblastic cell line, Meg-J, which showed prominant polyploidization and augmented platelet glycoprotein (GP) Ib expression after incubation with thrombopoietin (TPO, c-mpl ligand) and K252a (an indolocarbasole derivative). Under these conditions, we analyzed the expression of the transcription factors and observed that the expression of NF-E2 p45, but not those of GATA-1, GATA-2, Tal-1/SCL, Evi-1, and MafK, was increased after TPO and K252a stimulation. Gel-shift assay confirmed the enhanced binding activity to the NF-E2 site. The abolishment of NF-E2 p45 with NF-E2 antisense oligomers inhibited TPO plus K252a-induced polyploidization. These findings suggest that NF-E2 p45 is essential for the polyploidization of megakaryocytic cells.

Basic Helix-Loop-Helix Proteins↗

PubMed1998

Induction of fertile estrus in bitches using a sustained-release formulation of a GnRH agonist (leuprolide acetate).

A single subcutaneous injection of a sustained-release formulation of a potent GnRH agonist, leuprolide acetate (LA; [D-Leu6, Pro9NEt]-GnRH), was evaluated as a method of inducing fertile estrus in 12 mature anestrous and 6 prepubertal beagle bitches. The bitches were treated with microencapsulated LA (100 micrograms/kg, s.c.) at 120 or 150 d post partum, or at 1 yr of age, followed by a GnRH-analogue (fertirelin; [Pro9NEt]-GnRH, 3 micrograms/kg, i.m.) on the first day of induced estrus. Signs of estrus were seen within 10.3 +/- 0.9 d after LA administration in all bitches. The interestrous interval in 120- and 150-d post-partum bitches was shortened (P < 0.05) to 191 +/- 3 and 222 +/- 3 d, respectively, compared with 264 +/- 11 d in control bitches. All LA treated dogs demonstrated behavioral estrus and mated. Three of 6 (50%) at 120 d post partum, 6 of 6 (100%) at 150 d post partum and 5 of 6 (83%) of prepubertal (1-yr old) bitches then became pregnant and produced a mean litter size of 4.1 +/- 0.8 pups. A normal circulating estrogen and progesterone response pattern was observed in mature anestrous bitches. A prepubertal bitch that failed to become pregnant had a similar estrogen response pattern but an insufficient progesterone profile. The results suggest that microencapsulated LA can be useful in inducing fertile estrus in the domestic dogs.

Anestrus↗

PubMed1998

Flow cytometric analysis of Thy-1 expression in myelodysplastic syndrome.

We analyzed the expression of Thy-1 (CD90) antigen on CD34+ bone marrow mononuclear cells (BMMNC) obtained from 25 patients with myelodysplastic syndrome (MDS) by two-color flow cytometry. Five of nine patients (55.6%) with refractory anemia with excess of blasts (RAEB) and two of 16 (12.5%) with RAEB in transformation (RAEB-t) showed more than 20% of Thy-1 expression of their CD34+ BMMNC. Regarding chromosomal abnormalities, -5/5q- or -18 might be correlated with the expression of Thy-1 on CD34+ BMMNC in MDS. Nine patients were analyzed twice, once before and once after leukemic transformation and showed no significant change in Thy-1 expression. These results show that Thy-1 was expressed on CD34+ BMMNC in certain patients with MDS before leukemic transformation and that it was maintained during the disease progression. In contrast, expression of Thy-1 did not seem essential to the leukemic transformation in MDS though the patients with high Thy-1 expression might have poorer prognosis compared with those with low Thy-1 expression.

Adolescent↗

PubMed1998

Derivatives of WAY 100635 as potential imaging agents for 5-HT1A receptors: syntheses, radiosyntheses, and in vitro and in vivo evaluation.

Analogues of the potent and selective 5-HT1A ligand, WAY 100635, were synthesized and examined as potential candidates for imaging 5-HT1A receptors by positron emission tomography (PET). Several of the analogues displayed nanomolar affinity for the 5-HT1A receptor, comparable to WAY 100635. Three of these were examined in a model of human liver metabolism vis-à-vis WAY 100635. All showed a markedly lower propensity for amide hydrolysis than WAY 100635. Radiolabelling of these three potential PET radiotracers with carbon-11 was readily achieved from [11C]-iodomethane, and the newly synthesized radioligands were tested in vivo in rats for binding to 5-HT1A receptors. Whereas two of the ligands failed to bind to 5-HT1A receptors in vivo, one was successful. The latter, [11C]-7 [4-(2'-methoxyphenyl)-1-[2'-[N-(2'-pyridinyl)-2-bicyclo[2.2.2]octanec arboxamido]ethyl]-piperazine], showed good brain penetration, hippocampal:cerebellar ratios of 10:1 at 45 min postinjection. Blocking studies with a variety of drugs demonstrated that the binding of [11C]-7 in vivo was selective for 5-HT1A receptors. [11C]-7 is a promising candidate as a ligand for imaging 5-HT1A receptors by PET.

Animals↗

PubMed1998

Dietary cystine and liver triacylglycerols in rats: effects of dietary lysine and threonine.

Addition of excess cystine to a wheat gluten diet did not alter rat liver triacylglycerols or serum cholesterol. However, if the cystine-enriched diet was supplemented with lysine and threonine, rats accumulate triacylglycerols and show increased serum cholesterol. Increases in hepatic triacylglycerols can be prevented by the further addition of methionine. This diet further increases serum cholesterol. We conclude that accumulation of triacylglycerols in the liver might be due to an increased methionine requirement, induced by the addition of excess cystine, and therefore to choline deficiency.

Amino Acids↗

PubMed1998

CD34+/CD41a+ cells best predict platelet recovery after autologous peripheral blood stem cell transplantation.

Reliable markers for megakaryocytic reconstitution after peripheral blood stem cell transplantation (PBSCT) have not been established. To determine a convenient and reliable predictor, we measured the number of megakaryocyte progenitor cells in PBSC grafts by clonogenic and flow cytometric assays. Seventeen patients with hematological and solid malignancies were included in this study. For the clonogenic assay, we used thrombopoietin (TPO) as a growth factor to evaluate the maximum number of megakaryocyte progenitor cells. Using a flow cytometric assay, we examined the expression of platelet glycoproteins on CD34+ cells to count the number of megakaryocyte progenitor cells. We used buffer containing EDTA to prevent platelet adhesion to CD34+ cells and selected CD34+ cells by immunomagnetic beads. The best correlation was observed between the number of CD34+/CD41a+ cells and the time to platelet recovery (P = 0.0205), rather than the total number of CD34+ cells. In addition, a close correlation was observed between the number of CD34+/CD41a+ cells and colony-forming unit megakaryocyte (CFU-MK) (P = 0.0018). These observations suggest that the number of CD34+/CD41a+ cells is the best predictor for platelet reconstitution after PBSCT.

Adolescent↗

PubMed1998

Decay-accelerating factor (DAF) in stool specimens as a marker of disease activity in patients with ulcerative colitis (UC).

Colonic epithelial cells of patients with UC express DAF in relation to the severity of mucosal inflammation. The aim of this study was to determine whether this factor in stool could be used as a marker of disease activity in UC patients. Stool DAF was measured by use of an immunoassay in 181 stool specimens obtained from 55 patients with UC of various levels of disease activity. Stool DAF concentrations in patients whose UC was active (0.0-785.6 ng/g stool; median 47.1 ng/g; n = 115) were significantly higher than concentrations in patients whose disease was inactive (0.0-48.6 ng/g; median 0.0 ng/g; n = 66) (P < 0.0001). Values in active UC patients also were higher than those in control patients with diarrhoea (0.0-30.0 ng/g; median 0.0 ng/g; n = 26) (P < 0.0001) and in control subjects without apparent colorectal disease (0-20.4 ng/g; median 0.0 ng/g; n = 44) (P < 0.0001). The elevated levels of stool DAF obtained from UC patients in relapse declined markedly in specimens collected after the disease went into remission following medical therapy. Stool DAF levels correlated with the severity of endoscopic and histological findings and the degree of DAF expression on the colonic epithelia. Our results suggest that the measurement of stool DAF is useful as a non-invasive means of monitoring intestinal disease activity in patients with UC.

Adolescent↗