Biomedical subjects

M Kawabata

Publications and source records attributed to M Kawabata.

At least 73 records · Page 4Linked to original sources

PubMed2000

[An autopsy case of neurogenic pulmonary edema due to suicide by hanging].

A 43-year-old man died of pulmonary edema after hanging himself. His cardiac function and renal function were normal. No aspiration, trauma, or overhydration was present, and high doses of catecholamine had not been administered. Autopsy findings revealed hypoxic brain damage, cerebral edema and pyknosis of nerve cells in the medulla oblongata. These findings resulted in a diagnosis of neurogenic pulmonary edema. To our knowledge, there have been no previous reports of neurogenic pulmonary edema due to airway obstruction.

Adult↗

PubMed2000

Prevalence of antibodies to Toxoplasma gondii among urban and rural residents in the Philippines.

A survey of antibodies to Toxoplasma gondii was carried out among residents in urban (Metro Manila) and rural (Mindoro and Leyte) areas in the Philippines. A total of 1,173 serum samples were examined for Toxoplasma antibody by an ELISA method. The overall seropositivity was 11.1% (n=904, 12.4% in males, 10.0% in females) in Metro Manila, 61.2% (n=152, 63.3% in males, 53.1% in females) in Mindoro, and 30.1% (n=113, 34.3% in males, 22.5% in females) in Leyte, indicating significantly higher (p<0.001) seropositivities in rural than urban settings. No significant differences in seropositivities were observed between males and females. In each group, seropositivity tended to increase with age of the subjects.

Adolescent↗

PubMed2000

Effect of intestinal helminthiasis on nutritional status of schoolchildren.

This study was conducted in a rural agricultural area in Siniloan, Republic of the Philippines. The subjects were the school children. The nutritional status of 58 children infected with helminthiasis (Ascaris lumbricoides and Trichuris trichiura) was compared with that of 19 uninfected controls. Prevalence of Ascaris and Trichuris was 40.3% and 71.4% respectively, and 36.4% of infected children had both Ascaris and Trichuris infections. Statistically significant evidence of an adverse effect of helminthiasis on serum albumin levels was found, but no child had inadequate levels of other nutrients. Although helminthic infections increase the level of immunoglobulin E (IgE) in children endemically exposed to these parasites, there was no significant difference in the serum IgE among Ascaris or Trichuris infected groups in this study.

Adolescent↗

PubMed2000

Analysis of relationship between Anopheles subpictus larval densities and environmental parameters using Remote Sensing (RS), a Global Positioning System (GPS) and a Geographic Information System (GIS).

Remote Sensing (RS), a Global Positioning System (GPS) and a Geographic Information System (GIS) were used to analyze relationship between Anopheles subpictus larval densities and environmental parameters in the Sekotong district on Lombok Island, Indonesia. Distance from the coast to larval habitats, season and surface water were considered as environmental parameters for determining An. subpictus larval densities. Japanese Earth Resources Satellite (JERS) Visible and Near Infrared Radiometer (VNIR) satellite imagery for the area acquired by National Space Development Agency of Japan (NASDA) were used to detect water, which could be used to characterize larval habitats. Data on larval sampling sites obtained from a GPS were entered into a GIS for mapping larval habitats to measure distance between the coast and the larval habitats. A GIS was used for overlaying of data coverages (i.e., water distribution from RS data and larval habitats coupled with data on larval densities) to identify factors that may explain the spatial distribution patterns of larval densities. An. subpictus larval densities were significantly associated with season and distance from the coast to larval habitats. The rainy season and the distance from the coast to larval habitats were critical environmental determinants for presence of An. subpictus larvae in the study. In this paper, we investigated relationship between An. subpictus larval densities and the environmental parameters using RS/GPS/GIS to determine if these tools could be used to predict larval densities.

Animals↗

PubMed1999

c-Ski acts as a transcriptional co-repressor in transforming growth factor-beta signaling through interaction with smads.

Smads are intracellular signaling mediators of the transforming growth factor-beta (TGF-beta) superfamily that regulates a wide variety of biological processes. Among them, Smads 2 and 3 are activated specifically by TGF-beta. We identified c-Ski as a Smad2 interacting protein. c-Ski is the cellular homologue of the v-ski oncogene product and has been shown to repress transcription by recruiting histone deacetylase (HDAC). Smad2/3 interacts with c-Ski through its C-terminal MH2 domain in a TGF-beta-dependent manner. c-Ski contains two distinct Smad-binding sites with different binding properties. c-Ski strongly inhibits transactivation of various reporter genes by TGF-beta. c-Ski is incorporated in the Smad DNA binding complex, interferes with the interaction of Smad3 with a transcriptional co-activator, p300, and in turn recruits HDAC. c-Ski is thus a transcriptional co-repressor that links Smads to HDAC in TGF-beta signaling.

Acetyltransferases↗

PubMed1999

Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter.

Smads are signal transducers for members of the transforming growth factor-beta (TGF-beta) superfamily. Upon ligand stimulation, receptor-regulated Smads (R-Smads) are phosphorylated by serine/threonine kinase receptors, form complexes with common-partner Smad, and translocate into the nucleus, where they regulate the transcription of target genes together with other transcription factors. Polyomavirus enhancer binding protein 2/core binding factor (PEBP2/CBF) is a transcription factor complex composed of alpha and beta subunits. The alpha subunits of PEBP2/CBF, which contain the highly conserved Runt domain, play essential roles in hematopoiesis and osteogenesis. Here we show that three mammalian alpha subunits of PEBP2/CBF form complexes with R-Smads that act in TGF-beta/activin pathways as well as those acting in bone morphogenetic protein (BMP) pathways. Among them, PEBP2alphaC/CBFA3/AML2 forms a complex with Smad3 and stimulates transcription of the germline Ig Calpha promoter in a cooperative manner, for which binding of both factors to their specific binding sites is essential. PEBP2 may thus be a nuclear target of TGF-beta/BMP signaling.

Activin Receptors, Type I↗

PubMed1999

Presenilin 1 suppresses the function of c-Jun homodimers via interaction with QM/Jif-1.

Presenilin 1 (PS1) is the causative gene for an autosomal dominant familial Alzheimer's disease (AD) mapped to chromosome 14. Here we show that QM/Jun-interacting factor (Jif)-1, a negative regulator of c-Jun, is a candidate to mediate the function of PS1 in the cell. We screened for proteins that bind to PS1 from a human embryonic brain cDNA library using the two-hybrid method and isolated one clone encoding the QM/Jif-1 gene. The binding of QM/Jif-1 to full-length PS1 was confirmed in vitro by pull-down assay, and in vivo by immunoprecipitation assays with human samples, including AD brains. Immunoelectronmicroscopic analysis showed that QM/Jif-1 and PS1 are colocalized at the endoplasmic reticulum, and the nuclear matrix in human brain neurons. Chloramphenicol acetyltransferase assays in F9 cells showed that PS1 suppresses transactivation by c-Jun/c-Jun but not by c-Jun/c-Fos heterodimers, consistent with the reported function of QM/Jif-1. By monitoring fluorescent recombinant protein and by gel mobility shift assays, PS1 was shown to accelerate the translocation of QM from the cytoplasm to the nucleus and to thereby suppress the binding of c-Jun homodimer to 12-O-tetradecanoylphorbol-13- acetate (TPA)-responsive element (TRE). PS1 suppressed c-jun-associated apoptosis by retinoic acid in F9 embryonic carcinoma cells, whereas this suppression of apoptosis is attenuated by mutation in PS1. Collectively, the novel function of PS1 via QM/Jif-1 influences c-jun-mediated transcription and apoptosis.

Adult↗

PubMed1999

E1A inhibits transforming growth factor-beta signaling through binding to Smad proteins.

Smads form a recently identified family of proteins that mediate intracellular signaling of the transforming growth factor (TGF)-beta superfamily. Smads bind to DNA and act as transcriptional regulators. Smads interact with a variety of transcription factors, and the interaction is likely to determine the target specificity of gene induction. Smads also associate with transcriptional coactivators such as p300 and CBP. E1A, an adenoviral oncoprotein, inhibits TGF-beta-induced transactivation, and the ability of E1A to bind p300/CBP is required for the inhibition. Here we determined the Smad interaction domain (SID) in p300 and found that two adjacent regions are required for the interaction. One of the regions is the C/H3 domain conserved between p300 and CBP, and the other is a nonconserved region. p300 mutants containing SID inhibit transactivation by TGF-beta in a dose-dependent manner. E1A inhibits the interaction of Smad3 with a p300 mutant that contains SID but lacks the E1A binding domain. We found that E1A interacts specifically with receptor-regulated Smads, suggesting a novel mechanism whereby E1A antagonizes TGF-beta signaling.

Adenovirus E1A Proteins↗

PubMed1999

Two divergent signaling pathways for TGF-beta separated by a mutation of its type II receptor gene.

Transforming growth factor beta (TGF-beta) can inhibit epithelial cell growth and induce extracellular matrix formation through signal transduction via its two receptors and its downstream intracellular Smad proteins. We recently reported a germline mutation, i.e., substitution of methionine for threonine at codon 315 in the kinase subdomain IV, of the TGF-beta type II receptor gene in a kindred of hereditary nonpolyposis colorectal cancer without microsatellite instability and found that the mutant receptor abolished the signal transduction for growth inhibition by TGF-beta. In this study, we performed further functional analysis of this mutant receptor. The results showed that, in contrast to its failure to mediate growth inhibition by TGF-beta, the mutant receptor still retained the ability to induce one of the extracellular matrix proteins, plasminogen activator inhibitor type 1, upon TGF-beta treatment. However, coincident with its failure to mediate growth inhibition by TGF-beta, the mutant receptor failed to transcriptionally upregulate one of the cyclin-dependent kinase inhibitors, p15(INK4B), in response to TGF-beta. These data suggest that threonine 315 of the TGF-beta type II receptor is dispensable for extracellular matrix protein production, but is essential for the growth inhibition by TGF-beta, and that the lack of growth inhibition due to the mutant receptor is possibly mediated through its failure to upregulate p15(INK4B).

Amino Acid Sequence↗

PubMed1999

Positive and negative modulation of vitamin D receptor function by transforming growth factor-beta signaling through smad proteins.

Several lines of experiments demonstrated the interplay between the transforming growth factor-beta (TGF-beta) and vitamin D signaling pathways. Recently, we found that Smad3, a downstream component of the TGF-beta signaling pathway, potentiates ligand-induced transactivation of vitamin D receptor (VDR) as a coactivator of VDR (Yanagisawa, J., Yanagi, Y., Masuhiro, Y., Suzawa, M., Watanabe, M., Kashiwagi, K., Toriyabe, T., Kawabata, M., Miyazono, K., and Kato, S. (1999) Science 283, 1317-1321). Here, we investigated the roles of inhibitory Smads, Smad6 and Smad7, which are negative regulators of the TGF-beta/bone morphogenetic protein signaling pathway, on the Smad3-mediated potentiation of VDR function. We found that Smad7, but not Smad6, abrogates the Smad3-mediated VDR potentiation. Interaction studies in vivo and in vitro showed that Smad7 inhibited the formation of the VDR-Smad3 complex, whereas Smad6 had no effect. Taken together, our results strongly suggest that the interplay between the TGF-beta and vitamin D signaling pathways is, at least in part, mediated by the two classes of Smad proteins, which modulate VDR transactivation function both positively and negatively.

Animals↗

PubMed1999

Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300.

The cytokines LIF (leukemia inhibitory factor) and BMP2 (bone morphogenetic protein-2) signal through different receptors and transcription factors, namely STATs (signal transducers and activators of transcription) and Smads. LIF and BMP2 were found to act in synergy on primary fetal neural progenitor cells to induce astrocytes. The transcriptional coactivator p300 interacts physically with STAT3 at its amino terminus in a cytokine stimulation-independent manner, and with Smad1 at its carboxyl terminus in a cytokine stimulation-dependent manner. The formation of a complex between STAT3 and Smad1, bridged by p300, is involved in the cooperative signaling of LIF and BMP2 and the subsequent induction of astrocytes from neural progenitors.

Animals↗

PubMed1999

Multiple alternative transcripts of the human homologue of the mouse TRAD/R51H3/RAD51D gene, a member of the rec A/RAD51 gene family.

Yeast RAD51, a homologue of Escherichia coli recA, plays a crucial role in mitotic and/or meiotic recombination and in the repair of double-strand DNA breaks. We have identified unique multiple alternative transcripts of a human TRAD/R51H3/RAD51D gene, a member of the recA/RAD51 gene family. One of the transcripts encoded a 328-amino-acid protein with 83.0% overall amino acid identity and 98. 2% similarity with the mouse TRAD gene and had two nucleotide binding consensus sequences, motif A and motif B, conserved among members of this family. Other transcripts encoded truncated proteins with a partial N-terminal region of the orthologue or short proteins lacking internal sequences which contain nucleotide binding motifs. Northern blot analysis revealed that multiple transcripts of the human TRAD gene were expressed in various tissues and their distribution was not ubiquitous.

Alternative Splicing↗

PubMed1999

Convergence of transforming growth factor-beta and vitamin D signaling pathways on SMAD transcriptional coactivators.

Cell proliferation and differentiation are regulated by growth regulatory factors such as transforming growth factor-beta (TGF-beta) and the liphophilic hormone vitamin D. TGF-beta causes activation of SMAD proteins acting as coactivators or transcription factors in the nucleus. Vitamin D controls transcription of target genes through the vitamin D receptor (VDR). Smad3, one of the SMAD proteins downstream in the TGF-beta signaling pathway, was found in mammalian cells to act as a coactivator specific for ligand-induced transactivation of VDR by forming a complex with a member of the steroid receptor coactivator-1 protein family in the nucleus. Thus, Smad3 may mediate cross-talk between vitamin D and TGF-beta signaling pathways.

Animals↗

PubMed1999

Evaluation of contrast agents for delineation of vessel wall boundary by intracoronary ultrasound after coronary angioplasty in human.

We evaluated the potential for improving visualization at intervention sites using contrast-enhanced intracoronary ultrasound (ICUS) and the suitable contrast agents for this procedure in humans. In 37 patients, ICUS (30 MHz) was performed with intracoronary bolus injection (3 mL) of seven different contrast preparations and without the contrast agents (control) after coronary intervention. The contrast agents used were as follows: saline solution, standard iomeprol, standard ioxaglate, sonicated iomeprol, sonicated ioxaglate, 50% Albunex, and 100% Albunex. Homogeneous and complete opacification of the vessel lumen and false lumen was observed with sonicated ioxaglate, 50% and 100% Albunex. Shadowing was not observed at all with sonicated ioxaglate and was uncommon with 50% Albunex, whereas 100% Albunex caused shadowing in all cases. The coronary delineation rate with the other contrast agents was only 60%-70%, and the homogeneity and peak intensity were relatively low. Thus, sonicated ioxaglate and 50% Albunex both achieved good visualization, but the latter is more expensive, more difficult to handle, and takes longer to prepare. Of the agents we studied, sonicated ioxaglate appears to be best suited for contrast-enhanced ICUS. ICUS using suitable contrast agents could only visualize the large dissections and the strategy was changed according to the contrast-enhanced ICUS results in five cases. Thus, suitable contrast agents, e.g., sonicated ioxaglate, should be used during ICUS after intracoronary intervention.

Aged↗

PubMed1999

Intermittent bundle branch blocks in a patient with uncommon-type atrioventricular nodal reentrant tachycardia and enhanced atrioventricular nodal conduction.

We report on a patient with uncommon-type atrioventricular (AV) nodal reentrant tachycardia with a short tachycardia cycle length (235-270 ms), in whom transient wide QRS tachycardia with both left bundle branch block and right bundle branch block aberrancy were followed by narrow QRS complexes. In addition, His-ventricular (H-V) block and a sudden prolongation of the H-V interval occurred during the tachycardia. As the determinant of these unusual findings, the possibility that the anterograde limb of the reentry circuit has an enhanced AV nodal conduction property is discussed, as is the clinical significance of this type of tachycardia.

Adult↗

PubMed1999

BMP-4 and retinoic acid synergistically induce activation of caspase-9 and cause apoptosis of P19 embryonal carcinoma cells cultured as a monolayer.

In monolayer cultures of P19 EC cells treated with both all-trans retinoic acid (RA) and bone morphogenetic protein (BMP)-4 (RA/BMP-4 treatment), many non-adherent apoptotic cells and activated caspase-3-positive cells were observed, but they were not observed in cells treated with RA or BMP-4 alone. Consistent with the appearance of activated caspase-3-positive cells, BMP-4 and RA together induced processing of caspase-9, Ac-DEVD-MCA cleavage activity and DNA fragmentation. These three activities were observed infrequently or not at all when cells were treated with RA or BMP-4 alone. In the RA/BMP-4 treatment-induced apoptosis, caspase-9 was upstream of caspase-3 in the enzyme cascade, and the caspase-9 to -3 step was key in the apoptotic pathway. Bcl-xL inhibited processing of caspase-9, Ac-DEVD-MCA cleavage activity and DNA fragmentation induced by RA/BMP-4 treatment. However, unlike staurosporine-induced apoptosis, cytochrome c, which activates caspase-9, was not detected in the cytosol of RA/BMP-4-treated cells. RA and BMP-4 may activate caspase-9 through an apoptotic pathway other than the Apaf-1/cytochrome c pathway. The prominent decrease of X-chromosome-linked inhibitory apoptosis protein (XIAP) in the cytosol may explain the activation of caspase-9 induced by RA and BMP-4 treatment.

Animals↗

PubMed1999

Drosophila dSmad2 and Atr-I transmit activin/TGFbeta signals.

BACKGROUND: Much is known about the three subfamilies of the TGFbeta superfamily in vertebrates-the TGFbetas, dpp/BMPs, and activins. Signalling in each subfamily is dependent on both shared and unique cell surface receptors and Smads. In invertebrates, mutants for BMP pathway components have been extensively characterized, but thus far, evidence for an activin- or TGFbeta-like pathway has been lacking, preventing the use of the extensive genetic tools available for studying several key issues of TGFbeta signalling. RESULTS: Here we report the identification of dSmad2, a new Drosophila Smad which is most related to the activin/TGFbeta-pathway Smads, Smad2 and Smad3. We show that dSmad2 induces activin responsive genes in Xenopus animal cap assays. dSMAD2 is phosphorylated by ATR-I and PUNT, but not by activated THICK VEINS, and translocates to the nucleus upon activation. Furthermore, we show that dSMAD2 complexes with MEDEA only in the presence of ATR-I and PUNT. dSmad2 is expressed in the imaginal disks and in the outer proliferation centre of the larval brain, suggesting that it may have important proliferative and patterning roles during Drosophila development. CONCLUSION: Our data provide evidence for the existence of an activin/TGFbeta pathway in Drosophila. We show that dSmad2 participates in this pathway, and that it functions with Atr-I and punt. We show that Medea also participates in this pathway, indicating the conservation of roles for Co-Smads in diverse phyla. Expression patterns of dSmad2 suggest that it functions in imaginal disks and in the brain, in tissues that undergo extensive patterning and proliferation.

Activin Receptors↗

PubMed1999

Region between alpha-helices 3 and 4 of the mad homology 2 domain of Smad4: functional roles in oligomer formation and transcriptional activation.

BACKGROUND: Smad4 has a unique region of 35 amino acids between alpha-helices 3 and 4 (termed H3/4 loop) of the Mad homology (MH) 2 domain. In order to elucidate the functional importance of the H3/4 loop, we prepared chimeric constructs of Smad4 containing the region corresponding to the alpha-helix 3, H3/4 loop and alpha-helix 4 of different Smads, including a chimera containing that of Smad2 (Smad4-HL2). RESULTS: Smad4-HL2 constitutively induced the transcriptional activation of p3TP-Lux, a TGF-beta-responsive reporter construct. However, co-transfection of Smad2 with Smad4-HL2 did not induce a further increase in the activation of p3TP-Lux. Smad4-HL2 did not induce the activation of pAR3-Lux, which contains FAST1-binding sites and is activated by a complex composed of FAST1, Smad2 and Smad4. Smad4-HL2 formed a homo-oligomer more efficiently than wild-type Smad4 in mammalian cells. Moreover, Smad4-HL2 bound to DNA containing the Smad-binding sites with a gretaer affinity than the wild-type Smad4. CONCLUSION: Smad4-HL2 spontaneously forms a homo-oligomer, which may bind to DNA with relatively high affinity and induce transcriptional activation of p3TP-Lux. The H3/4 loop of Smad4 may thus play a role in precluding the spontaneous oligomer formation of Smad4.

Animals↗