Genetic differentiation of a measles virus isolated from a case occurring 15 days after measles vaccination.
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Amino Acid Substitution↗
Biomedical subjects
M Noda
Publications and source records attributed to M Noda.
[Pneumatosis intestinalis after allogeneic bone marrow transplantation for acute lymphocytic leukemia].
A 45-year-old man was diagnosed as having acute lymphocytic leukemia (ALL) in February 1997. Complete remission was achieved by chemotherapy, and allogeneic BMT from his HLA-identical sister was performed on November 13, 1997. He developed acute GVHD (grade II), but quickly recovered after methyl-PSL pulse therapy. On June 5, 1998--day 202 after BMT--abdominal pain developed. X-ray and CT examinations showed pneumatosis intestinalis, pneumoperitoneum, pneumomediastinum and abdominal free air. We performed oxygen administration and methyl-PSL pulse therapy, and this quickly improved the symptoms. Corticosteroid and chronic GVHD were thought to be the causative factors of pneumatosis intestinalis in this case. Although pneumatosis intestinalis is relatively rare, it is one of the important potential complications that can occur after allogeneic BMT.
Bone Marrow Transplantation↗
[Successful non-invasive positive pressure ventilation therapy to acute respiratory failure after volume reduction surgery for patient with severe emphysema: report of a case].
A 55-year-old man consulted our hospital because of short of breath. Chest CT showed low attenuation areas and we diagnosed his illness as a chronic respiratory failure by chronic lung empysema. He was perfomed bilateral lung volume reduction surgery (VRS), after a few days who was in serious acute respiratory failure. He was treated by non-invasive positive pressure ventilation (NIPPV) for those. After that general condition and arterial blood gas data was improved. NIPPV may be one of the effective tools for acute respiratory failure after VRS.
Acute Disease↗
[Cancer of the intestine].
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Age Factors↗
[Bone metabolism and angiogenesis].
Bone metabolism is regulated not only by the nutrition supplied by vessel but also by the signals from the cells in vascular tissues. Identification of such signaling molecules has been the major issue in the field of research on the relationship between bone and vasculatures. This review touches on the recent findings on the expression and functions of such signaling molecules including VEGF, MMP and non-collagenous bone matrix proteins.
English Abstract↗
[The meaning of phosphate in bone formation].
Bone formation requires phosphate to calcify the osteoid produced by osteoblasts, Pit-1, a natrium-phosphate cotransporter, is expressed in osteoblasts and its expression levels are regulated developmentally and also by hormones and cytokines. Another type of phosphate transporter is expressed in osteoclasts and its function is required for bone resumption. These observations suggest that phosphate transport into the bone cells may play a role in regulation of bone formation and resorption in vivo and in the pathological situation in patients with bone diseases.
English Abstract↗
Negative regulation of BMP/Smad signaling by Tob in osteoblasts.
Bone morphogenetic protein (BMP) controls osteoblast proliferation and differentiation through Smad proteins. Here we show that Tob, a member of the emerging family of antiproliferative proteins, is a negative regulator of BMP/Smad signaling in osteoblasts. Mice carrying a targeted deletion of the tob gene have a greater bone mass resulting from increased numbers of osteoblasts. Orthotopic bone formation in response to BMP2 is elevated in tob-deficient mice. Overproduction of Tob represses BMP2-induced, Smad-mediated transcriptional activation. Finally, Tob associates with receptor-regulated Smads (Smad1, 5, and 8) and colocalizes with these Smads in the nuclear bodies upon BMP2 stimulation. The results indicate that Tob negatively regulates osteoblast proliferation and differentiation by suppressing the activity of the receptor-regulated Smad proteins.
Alleles↗
Overexpression of Cas-interacting zinc finger protein (CIZ) suppresses proliferation and enhances expression of type I collagen gene in osteoblast-like MC3T3E1 cells.
Osteoblasts are the cells which form bone under the regulation not only by hormones and cytokines but also by ECM molecules via their attachment. To obtain insights into the role of intracellular signaling molecules operating to mediate the attachment-related regulation of osteoblastic functions, we investigated in osteoblast-like MC3T3E1 cells the effects of the overexpression of CIZ, a novel signaling protein which interacts with p130Cas. In MC3T3E1 cells, CIZ mRNA is expressed constitutively. Endogenous CIZ was localized in the MC3T3E1 cells with relatively high levels of accumulation at the attachment sites when the cells were cultured on fibronectin, collagen, or BSA. CIZ overexpression increased the number of adhesion plaques and reduced proliferation of the cells compared to that of control cells transfected with an empty vector. Furthermore, CIZ overexpression enhanced type I collagen mRNA expression, the most abundant constituent of bone matrix and a major product of osteoblasts. Analysis of the promoter region of type I collagen gene identified the presence of a consensus CIZ-binding sequence, which indeed conferred responsiveness to CIZ overexpression to a heterologous promoter. These data indicate that CIZ acts as a novel regulatory molecule in controlling osteoblastic function.
Animals↗
Differential localization of septins in the mouse brain.
We have carried out a comparative immunohistochemical study on four members of the septin family, CDCrel-1, Septin6, CDC10, and H5, which are abundantly expressed in the adult mouse brain. We found that each septin showed overlapping but distinct distribution at the levels of light and electron microscopy. CDCrel-1 was abundant in inhibitory presynaptic terminals and associated with GABAergic vesicles in the thalamus, globus pallidus, and cerebellar nuclei. Septin6 was associated with synaptic vesicles in various brain regions, including glomeruli of the olfactory bulb. CDC10 was diffusely expressed in the brain and was localized beneath presynaptic membrane and astroglial processes. H5 was localized in the astroglial processes in some specific brain regions. The differential expression and subcellular localization of these septins indicates that a given neuron or glial cell expresses a specific set of septin monomers and that the resulting septin complexes with distinct compositions may play distinct roles in the brain.
Animals↗
Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact.
T cell differentiation in the thymus is driven by positive selection through the interaction of alphabeta T cell receptors (TCRs) with self-peptides bound to self-major histocompatibility complex molecules, yet the influence of the peptide sequence on this process remains unknown. To address this issue, we have compared CD4(+) T cell differentiation between two sets of mouse lines in which MHC class II I-A(b) molecules are occupied with either Ealpha chain-derived peptide ((p)Ealpha) or its variant, (p)60K, with one amino acid substitution from leucine to lysine at P5 residue of TCR contacts. Here, we show that despite the comparable expression of I-A(b)-peptide complex in the thymus, this substitution from leucine to lysine affects efficiency of positive selection, resulting in extremely small numbers of CD4(+) T cells to be selected to mature on I-A(b)-(p)60K complex. Furthermore, we show that, although I-A(b)-(p)Ealpha complex selects diverse T cells, T cell repertoire shaped by I-A(b)-(p)60K complex is markedly constrained. Our findings thus suggest that positive selection is both specific and degenerate, depending on the amino acid residues at TCR contacts of the selecting self-peptides.
Amino Acid Sequence↗
Molecular characterization of CRMP5, a novel member of the collapsin response mediator protein family.
The CRMP (collapsin response mediator protein) family is thought to play key roles in growth cone guidance during neural development. The four members (CRMP1-4) identified to date have been demonstrated to form hetero-multimeric structures through mutual associations. In this study, we cloned a novel member of this family, which we call CRMP5, by the yeast two-hybrid method. This protein shares relatively low amino acid identity with the other CRMP members (49-50%) and also with dihydropyrimidinase (51%), whereas CRMP1-4 exhibit higher identity with each other (68-75%), suggesting that CRMP5 might be categorized into a third subfamily. The mouse CRMP5 gene was located at chromosome 5 B1. Northern blot and in situ hybridization analyses indicated that CRMP5 is expressed throughout the nervous system similarly to the other members (especially CRMP1 and CRMP4) with the expression peak in the first postnatal week. Association experiments using the yeast two-hybrid method and co-immunoprecipitation showed that CRMP5 interacts with dihydropyrimidinase and all the CRMPs including itself, except for CRMP1, although the expression profile almost overlaps with that of CRMP1 during development. These results suggest that CRMP complexes in the developing nervous system are classifiable into two populations that contain either CRMP1 or CRMP5. This indicates that different complexes may have distinct functions in shaping the neural networks.
Amino Acid Sequence↗
Hexamminecobalt(III) chloride inhibits glucose-induced insulin secretion at the exocytotic process.
Hexamminecobalt(III) (HAC) chloride was found to have a potent inhibitory effect on glucose-induced insulin secretion from pancreatic islets. HAC at 2 mm inhibited the secretion in response to 22.2 mm glucose by 90% in mouse islets. Perifusion experiments revealed that the first phase of insulin secretion was severely suppressed and that the second phase of secretion was completely abrogated. Removal of HAC from the perifusate immediately restored insulin secretion with a transient overshooting above the normal level. However, HAC failed to affect glucose-induced changes in d-[6-(14)C]glucose oxidation, levels of reduced forms of NAD and NADP, mitochondrial membrane potential, ATP content, cytosolic calcium concentration, or calcium influx into mitochondria. Furthermore, HAC inhibited 50 mm potassium-stimulated insulin secretion by 77% and 10 microm mastoparan-stimulated insulin secretion in the absence of extracellular Ca(2+) by 80%. The results of a co-immunoprecipitation study of lysates from insulin-secreting betaHC9 cells using anti-syntaxin and anti-vesicle-associated membrane protein antibodies for immunoprecipitation or Western blotting suggested that HAC inhibited disruption of the SNARE complex, which is normally observed upon glucose challenge. These results suggest that the inhibitory effect of HAC on glucose-induced insulin secretion is exerted at a site(s) distal to the elevation of cytosolic [Ca(2+)], possibly in the exocytotic machinery per se; and thus, HAC may serve as a useful tool for dissecting the molecular mechanism of insulin exocytotic processes.
Adenosine Triphosphate↗
Mitf is expressed in osteoclast progenitors in vitro.
Microphthalmia mutant (mi/mi) mice reveal defects in osteoclastogenesis and exhibit osteopetrosis. However, there have been no studies to test the importance of Mitf in in vitro osteoclastogenesis using the cells derived from mi/mi mice. Therefore, we investigated in vitro osteoclastogenesis using the cells derived from mi/mi mice. We cocultured spleen cells prepared from either wild-type or mi/mi mice with ST2 or TM8 stromal cells and found that formation of TRAP-positive cells was significantly reduced in the cocultures of mi/mi spleen cells compared to wild-type spleen cells in the presence of 1,25(OH)(2) vitamin D(3) (vitamin D). We further investigated Mitf expression by Northern blot analysis in relation to the differentiation of osteoclasts using the cocultures of bone marrow cells with stromal/osteoblastic cells and found positive correlation in expression levels of c-fms and Mitf. Moreover, osteoclast-progenitor-like C7 cells expressed c-fms as well as Mitf mRNAs when cultured alone. C7 cells also expressed Mitf protein in their nuclei. Similar results were obtained when we used primary spleen cells, which differentiate into osteoclasts cultured in the presence of M-CSF and RANKL/ODF. Mitf expression levels in the cocultures of C7 cells and ST2 cells were not changed by treatment with vitamin D in the presence or absence of dexthamethasone. These results suggest that Mitf is expressed in osteoclast progenitors and its presence facilitates osteoclastogenesis.
Animals↗
Nav2/NaG channel is involved in control of salt-intake behavior in the CNS.
Na(v)2/NaG is a putative sodium channel, whose physiological role has long been an enigma. We generated Na(v)2 gene-deficient mice by inserting the lacZ gene. Analysis of the targeted mice allowed us to identify Na(v)2-producing cells by examining the lacZ expression. Besides in the lung, heart, dorsal root ganglia, and Schwann cells in the peripheral nervous system, Na(v)2 was expressed in neurons and ependymal cells in restricted areas of the CNS, particularly in the circumventricular organs, which are involved in body-fluid homeostasis. Under water-depleted conditions, c-fos expression was markedly elevated in neurons in the subfornical organ and organum vasculosum laminae terminalis compared with wild-type animals, suggesting a hyperactive state in the Na(v)2-null mice. Moreover, the null mutants showed abnormal intakes of hypertonic saline under both water- and salt-depleted conditions. These findings suggest that the Na(v)2 channel plays an important role in the central sensing of body-fluid sodium level and regulation of salt intake behavior.
Administration, Oral↗
Results of pharmacokinetic modulating chemotherapy in combination with hepatic arterial 5-fluorouracil infusion and oral UFT after resection of hepatic colorectal metastases.
BACKGROUND: Pharmacokinetic modulating chemotherapy (PMC) is a new therapeutic concept in combination with continuous 5-fluorouracil (5-FU) infusion and UFT. UFT enhanced plasma 5-FU concentration and antitumor effects during 5-FU infusion. The authors report on their experiences with arterial 5-FU infusion and UFT after resection of hepatic colorectal secondaries. METHODS: Fifty-eight patients were divided into two groups after hepatectomy. Group A, 30 patients, underwent hepatic arterial infusion (HAI) via implantable port system with perfusion 5-FU for 2 consecutive days per week at 600 mg/m(2)/day, and oral administration of UFT at 400 mg/day for 5-7 days per week, repeated 10 times, and Group B, 28 patients, underwent oral administration of UFT at 400 mg/day for 6 months. All the patients were managed at the outpatient clinic at Hyogo College of Medicine, and recurrence, survival, and toxicity were documented. Plasma 5-FU concentrations during chemotherapy were detected using high performance liquid chromatography. RESULTS: Maximum plasma concentrations of 5-FU in Group A reached 144.0 ng/mL and in Group B 58.7 ng/mL. Cumulative 5-year survival rate after hepatectomy in Group A was 59% and in Group B was 27%. (P = 0.00001) HAI-PMC drastically decreased hepatic recurrence (median hepatic recurrence free times were 34.2 months in Group A vs. 18.4 months in Group B; P = 0.00002). Grade 3 toxicity in Group A was found in 3 patients CONCLUSIONS: Pharmacokinetic modulating chemotherapy was designed as a uracil-related biochemical modulation. HAI-PMC significantly decreased hepatic recurrence after curative resection. This new chemotherapy concept significantly improved prognosis in patients with hepatic colorectal metastases.
Administration, Oral↗
Tissue factor pathway inhibitor-2 suppresses the production of active matrix metalloproteinase-2 and is down-regulated in cells harboring activated ras oncogenes.
A human placenta cDNA expression library was screened for genes inducing flat reversion when transfected into a v-K-ras-transformed NIH3T3 cell line, DT. One such gene was found to encode a Kunitz-type serine protease inhibitor, tissue factor pathway inhibitor-2 (TFPI-2). While the TFPI-2 mRNA can be detected in normal human fibroblasts (MRC-5), it is down-regulated in MRC-5 cells expressing an activated H-ras oncogene and in the human fibrosarcoma cell line, HT1080. Restored expression of the TFPI-2 gene in HT1080 cells resulted in the suppression of matrix invasion activity in vitro with concomitant decrease in the relative amount of active matrix metalloproteinase-2 secreted from the cells. When DT cells were cultured in the presence of conditioned medium and extracellular matrix prepared from TFPI-2-transfected HT1080 cells, increased attachment and flat reversion were observed. These results suggest that TFPI-2 may be required for the maintenance of the integrity of extracellular matrix in normal tissues and its down-regulation as a result of oncogene activation may contribute to the malignant phenotypes of tumor cells.
Animals↗
Novel proteinaceous toxins from the box jellyfish (sea wasp) Carybdea rastoni.
During summer and autumn, the box jellyfish (sea wasp) Carybdea rastoni is one of the most bothersome stinging pests to swimmers and bathers on the Japanese coast. Two labile but potent hemolytic toxins from the tentacles of Carybdea rastoni were isolated in their active forms using newly developed purification methods. The molecular masses of the isolated C. rastoni toxin-A and toxin-B (CrTX-A and CrTX-B) are 43 and 46 kDa, respectively, as calculated from SDS-PAGE. In the present study, we sequenced the full-length cDNA (1600 bp), which encodes both CrTX-A and CrTX-B. The deduced 450 amino acid sequence of the CrTXs, showed no significant homology with any known protein. This report presents the first complete sequence of a proteinaceous jellyfish toxin. Furthermore, it was revealed that CrTX-A was primarily localized in the nematocyst, whereas CrTX-B was detected only in the tentacle. Because the nematocyst is the organ responsible for the cnidarian sting, the remainder of the study focused on the toxicity of CrTX-A. We found that CrTX-A was fatally toxic to mice at 20 microg/kg (i.v.) and crayfish at 5 microg/kg (i.p.). Subcutaneously injected CrTX-A (0.1 microg) caused inflammation of mouse skin. These results showed that CrTX-A is responsible for the cutaneous inflammation observed in humans stung by C. rastoni.
Animals↗
Identification and expression of a novel 3'-exon of mouse Runx1/Pebp2alphaB/Cbfa2/AML1 gene.
Cbfa1 (recently renamed as Runx2) is prerequisite for the differentiation of osteoblasts that play a central role in regulation of bone metabolism. Runx transcription factors belong to Drosophila pair rule gene "runt" family that also play critical roles during the development of hematopoietic tissues or insect bodies. To identify novel sequences related to Runx (Cbfa) genes, we screened a 11 d.p.c (days postcoitum) mouse embryonic cDNA library using a probe corresponding to Runx2 (Cbfa1) runt domain and identified a novel cDNA fragment. This cDNA (521-41) is about 2.4 kb in length and contains a sequence identical to the N-terminal half of mouse Runx1 (Pebp2alphaB/Cbfa2/AML1b) and a novel protein coding sequence in the C-terminal region. High expression levels of 521-41 mRNA were observed during the early mouse embryogenesis. In adult mice, 521-41 mRNA was expressed ubiquitously in lumbar vertebrae, brain, kidney, heart, muscle, and ovary. We also found that 521-41 mRNA was constitutively expressed in an osteoblast-like cell line, MC3T3E1. These data indicate that 521-41 gene is a novel splicing variant of mouse Runx1 which is expressed in skeletal tissues and osteoblast-like cells.
Alternative Splicing↗