Search PubMed⌕ Search

Biomedical subjects

K Iwai

Publications and source records attributed to K Iwai.

At least 91 records · Page 5Linked to original sources
PubMed1997

Mitogen-inducible SIPA1 is mapped to the conserved syntenic groups of chromosome 19 in mouse and chromosome 11q13.3 centromeric to BCL1 in human.

Sipa1, previously called Spa1, is transcriptionally induced in the murine lymphoid cells following mitogenic stimulation and encodes a protein with a domain related to Rap1 GTPase activating protein (Rap1GAP) at the N-terminus and to PEST sequences followed by a leucine zipper motif at the C-terminus. Herein mouse genomic Sipa1, which consisted of 16 exons, was cloned. Gene linkage analysis using (BXD) recombinant inbred strains indicated that Sipa1 was mapped to the most centromeric region of chromosome 19 syntenic with the long arm of human chromosome 11. Human SIPA1 cDNA exhibited a striking homology to that of mouse throughout the entire region, with the overall identity being 90% at the amino acid level. Human genomic clones, which hybridized with both mouse and human SIPA1 cDNA but not with RAP1GAP cDNA, were then isolated. Fluorescence in situ hybridization (FISH) analysis using the human genomic clones indicated that SIPA1 was indeed mapped to chromosome 11q13, most likely to the 11q13.3 subregion. It was further indicated by double-color FISH that SIPA1 was located in the centromeric neighborhood of CCND1/ PRAD1, a presumed BCL1 oncogene.

Animals↗
PubMed1997

Lung tumor induced by long-term inhalation or intratracheal instillation of diesel exhaust particles.

A series of long-term inhalation studies of diesel exhaust and intratracheal instillation of diesel particles was conducted on female SPF F344 rats. A particulate but not gaseous component in the inhalation studies provoked inflammatory changes and tumors in the lung, and the intratracheally instilled particles showed similar findings. Adenoma and adenocarcinoma were the main histologic types of the tumors which developed and they showed the phenotype of surfactant apoprotein-producing cells, suggesting that the tumor cell origin was a Type II alveolar cell. The tumor incidence rate correlated with the cumulative concentration of inhaled particles per week and with the amount of particles deposited in the lung. In the instillation studies, the carbon core of diesel particles obtained after exhaustive extraction of tarry matter showed a slightly lower positive rate of lung tumor formation than the rate in untreated diesel particles, indicating an important role of carbon core in the diesel particle-induced tumor. In the intratracheal instillation studies, point mutation of K-ras oncogene was detected in a significant percentage in the tumor cells.

Adenocarcinoma↗
PubMed1997

Prethrombotic state due to hypercoagulability in patients with permanent transvenous pacemakers.

Venous thrombosis is a relatively usual but serious complication of permanent transvenous pacing. However, the pathogenesis has not been defined. To clarify underlying abnormalities in the coagulation-fibrinolysis system in patients with permanent transvenous pacemakers, we measured serum levels of fibrinopeptide A (FPA), thrombin-antithrombin III complexes (TATs), plasmin-alpha 2 plasmin inhibitor complexes (PICs), D-dimer (D-D), beta-thromboglobulin (beta-TG), and platelet factor 4 (PF4) in 53 patients with permanent transvenous pacemakers and 10 control subjects. The patients were divided into two groups, as follows, according to the presence of mural thrombus documented along the pacing lead(s) by digital subtraction angiography and transesophageal echocardiography: Group Th (-), patients without venous route thrombus; and Group Th (+), patients with venous route thrombus. FPA and TAT levels increased significantly even in Group Th (-), and further increased in Group Th (+) compared with control subjects (FPA: 7.5 +/- 4.9, 15.3 +/- 8.8 vs 3.0 +/- 1.4 ng/mL, respectively, P < 0.05; TAT: 2.9 +/- 1.3, 4.8 +/- 2.3 vs 1.7 +/- 0.6 ng/mL, respectively, P < 0.05). There were no differences in levels of D-D, PIG, beta-TG, and PF4 among control subjects, Group Th (-), and Group Th (+). These findings suggest that the hypercoagulable state appears in patients with permanent transvenous pacemakers, even without apparent venous thrombosis. The patients with permanent transvenous pacemakers are thought to be in the prethrombotic state even if they have no venous route thrombosis.

Adult↗
PubMed1997

Talc and amosite/crocidolite preferentially deposited in the lungs of nonoccupational female lung cancer cases in urban areas of Japan.

To analyze the correlation between asbestos lung burden and lung cancer, lungs of 211 female cases with and without lung cancer were examined. Phase-contrast microscopic (PCM) counting of ferruginous (FBs) and uncoated fibers (UFs), which had length longer than 5 microns and aspect ratios greater than 3:1, revealed a significantly higher level of FBs plus UFs in urban lung cancer cases than urban non-lung cancer cases (1380.5 vs. 550.3; p < 0.001). No difference was noted between rural lung cancer and non-lung cancer cases. Analytical electron microscopic studies identified various kinds of mineral fibers with an aspect ratio greater than 3:1 in the lung tissue including chrysotile, actinolite/tremolite, amosite/crocidolite, fibrous talc, mica, silica, iron, wollastonite, chlorite, kaoline, and others. The most frequently detected fibers were thin, short chrysotile fibers, most of which could not be found by PCM, followed by relatively thick, long actinolite/tremolite fibers, fibrous talc, and in a smaller number, amosite/crocidolite of intermediate length and width. Amosite/crocidolite and fibrous talc counts in urban lung cancer cases were greater than those of urban non-lung cancer cases, rural lung cancer, and rural non-lung cancer cases; these findings were consistent with PCM analysis. Therefore, it is suggested that fibers detected in PCM observation may be mainly amosite/crocidolite with some parts fibrous talc and that fibrous talc in urban environments may be another candidate for carcinogenic or cocarcinogenic factors of female lung cancer.

Adult↗
PubMed1996

Identification of a conserved and functional iron-responsive element in the 5'-untranslated region of mammalian mitochondrial aconitase.

Iron-responsive elements (IREs) are RNA stem-loop motifs found in genes of iron metabolism. When cells are iron-depleted, iron regulatory proteins (IRPs) bind to IREs in the transcripts of ferritin, transferrin receptor, and erythroid amino-levulinic acid synthetase. Binding of IRPs to IRE motifs near the 5' end of the transcript results in attenuation of translation while binding to IREs in the 3'-untranslated region of the transferrin receptor results in protection from endonucleolytic cleavage. Iron deprivation results in activation of IRE binding activity, whereas iron replete cells lose IRE binding activation. Here, we report the identification of a conserved IRE in the 5'-untranslated region of the transcript of the citric acid cycle enzyme mitochondrial aconitase from four different mammalian species. The IRE in the transcript of mitochondrial aconitase can mediate in vitro translational repression of mitochondrial aconitase by IRPs. Furthermore, levels of mitochondrial aconitase are decreased in mice maintained on a low iron diet, whereas levels of mRNA remain unchanged. The decrease in levels of mitochondrial aconitase is likely due to activation of IRP binding and consequent attenuation of translation. Thus, expression of the iron-sulfur protein mitochondrial aconitase and function of the citric acid cycle may be regulated by iron levels in cells.

Aconitate Hydratase↗
PubMed1996

Differences in the RNA binding sites of iron regulatory proteins and potential target diversity.

Posttranscriptional regulation of genes of mammalian iron metabolism is mediated by the interaction of iron regulatory proteins (IRPs) with RNA stem-loop sequence elements known as iron-responsive elements (IREs). There are two identified IRPs, IRP1 and IRP2, each of which binds consensus IREs present in eukaryotic transcripts with equal affinity. Site-directed mutagenesis of IRP1 and IRP2 reveals that, although the binding affinities for consensus IREs are indistinguishable, the contributions of arginine residues in the active-site cleft to the binding affinity are different in the two RNA binding sites. Furthermore, although each IRP binds the consensus IRE with high affinity, each IRP also binds a unique alternative ligand, which was identified in an in vitro systematic evolution of ligands by exponential enrichment procedure. Differences in the two binding sites may be important in the function of the IRE-IRP regulatory system.

Alternative Splicing↗
PubMed1996

Mouse embryonic submandibular gland epithelium loses its tissue integrity during early branching morphogenesis.

During the development of the mouse submandibular gland, the epithelium undergoes not only shape changes to produce extensively branched lobules and stalk, but also changes in cell arrangement from a cell mass to a cavitated cell sheet. The present study examined the organization in the developing epithelium of intercellular adhesion systems and of actin-containing microfilaments. E-cadherin and beta-catenin, which are components of cell-to-cell adherens junctions in epithelial cells, were distributed along the cell periphery of almost the entire epithelium of the submandibular gland at all stages examined and were mainly localized at the apical region of the oral epithelium. Actin-containing microfilaments, which are associated with cell-to-cell adherens junctions, showed a distribution similar to that of those molecules. In contrast, although the distributions of desmoplakins I/II, major desmosomal proteins, and ZO-1 (a tight junction protein) were seen in the oral epithelium and proximal stalk of the submandibular gland epithelium, signals representing these molecules were absent from or much reduced in the submandibular gland epithelium of the cell mass at the 12- and 13-day stages. In the 14-day gland, they strongly appeared in the cells facing the appearing lumens, whereas they were weakly scattered within the terminal lobules that were still a part of the cell mass. These findings suggest that cell-to-cell adhesion systems are differentially regulated during the epithelial morphogenesis of the submandibular gland and that the integrity of the submandibular gland epithelium is lost during the early stages of development, indicating the tissue to be a rather plastic structure.

Actins↗
PubMed1996

Recovery of impaired left ventricular function in patients with acute myocardial infarction is predicted by the discordance in defect size on 123I-BMIPP and 201Tl SPET images.

A discrepancy between myocardial perfusion defect and wall motion abnormalities is frequently found early after coronary reperfusion in patients with acute myocardial infarction. The purpose of this study was to assess recovery of impaired left ventricular function by reference to the discordance in defect size between myocardial fatty acid uptake and myocardial perfusion using combined single-photon emission tomographic (SPET) imaging early after coronary perfusion therapy. In 37 patients with acute myocardial infarction, iodine-123 15-(p-iodophenyl)-3(R, S)-methylpentadecanoic acid (BMIPP) and thallium-201 SPET scans were performed early after coronary reperfusion. A severity score was determined from the extent of the imaging defect with each tracer. Left ventricular wall motion score (WMS) and ejection fraction (EF) were obtained at admission and at 4 weeks after the onset of infarction. In 32 of the 37 patients, discordance in defect sizes delineated with the two SPET studies was found during the acute stage. The severity score for BMIPP was larger than that for 201Tl during the acute stage (7. 7+/-2.4 vs 4.4+/-2.5, P <0.001). There was a fair correlation between the severity score for BMIPP and WMS (r=0.82, P <0.0001), but a poor correlation between that for 201Tl and WMS. The extent of discordance in severity scores between BMIPP and 201Tl during the acute stage correlated well with the extent of the improvement in WMS (r=0.86, P <0.0001) and that of EF (r=0.85, P <0.0001). We conclude that the discordance in defect size on BMIPP and 201Tl SPET images during the acute stage of infarction is an early predictor of the viability of the myocardium at risk of infarction.

Fatty Acids↗
PubMed1996

Recovery of apparent diffusion coefficient after ischemia-induced spreading depression relates to cerebral perfusion gradient.

BACKGROUND AND PURPOSE: Transient decreases of the apparent diffusion coefficient (ADC) of water as measured by fast diffusion-weighted imaging (DWI) in the ischemic border zone are thought to reflect cellular swelling associated with spreading depression. DWI and dynamic contrast-enhanced MRI were applied to study the characteristics of spreading depression and the correlation between ADC recovery time and tissue perfusion in focal ischemia. METHODS: Serial DWI was performed during remote middle cerebral artery occlusion in rats (n = 5) with an echo-planar imaging technique. ADC maps were calculated and ADC values displayed as a function of time in user-defined regions of interest with a time resolution of 12 to 16 seconds. Dynamic contrast-enhanced MRI was performed for qualitative correlation of ADC changes with tissue perfusion. RESULTS: Recovery time of transient ADC decreases correlated with the degree of the perfusion deficit (r = .81, P < .001). Slowly recovering ADC declines were found close to the ischemic core and correlated with severe perfusion deficit, while short-lasting ADC declines were typically found in moderately malperfused or normal tissue. Transient ADC decreases originated in the subcortical and cortical ischemic border zones and propagated along the cortex with a velocity of 2.9 +/- 0.9 mm/min. CONCLUSIONS: The variation in the recovery time of transient ADC decreases in the ischemic periphery reflects the gradient of the tissue perfusion. Severely delayed recovery time after spreading depression is thought to represent the ischemic penumbra.

Animals↗
PubMed1996

Superior vena cava syndrome due to a permanent transvenous pacing lead.

Superior vena cava (SVC) syndrome after pacemaker implantation is a very rare complication. We present a 56-year-old man with severe swelling of the face, neck, and upper arms about 6 years after pacemaker implantation. Digital subtraction angiography showed occlusion of the left innominate vein and severe stenosis of the SVC. The patient eventually required surgical treatment, since anticoagulant therapy and balloon venoplasty were not effective. We conclude that surgical repair is the most effective method for treating similar patients.

Humans↗
PubMed1996

Clinical presentation of pulmonary tuberculosis associated with acquired immunodeficiency syndrome in metropolitan Tokyo.

The clinical features of pulmonary tuberculosis associated with acquired immunodeficiency syndrome (AIDS) in Japan were surveyed utilizing questionnaires completed by 48 institutes around the Tokyo metropolitan area. We found 11 Japanese and six foreign patients. The average number of patients per institute was 0.37. The Japanese patients had advanced human immunodeficiency virus (HIV) infection. A middle aged man, with fever and cough, nonspecific chest X-ray infiltrates, decreased lymphocyte counts, and a negative tuberculin skin test was the typical presentation of the Japanese patients. The clinical diagnosis was often difficult. The smear positive rate was high among those from whom smears were obtained, suggesting high communicability. None of the isolates indicated multidrug-resistant tuberculosis at the time of diagnosis. In conclusion, sputum smear and culture remain the keys to diagnosing tuberculosis in patients with AIDS, although the clinical picture may be atypical for pulmonary tuberculosis.

Acquired Immunodeficiency Syndrome↗
PubMed1996

[Chemical evaluation and consideration on the traditional drug "ULUUS" (2)].

Traditional patent medicine named "ULUUS" has been regarded to be the first Dutch precipitation with a western name in Japan. It was found that this drug consists of Rhubarb mainly, and it contained high amounts of effective compounds as for the traditional sample that has been stored for more than 100 years. In fact, a dose of this medicine was supposed to cause a laxative effect.

History, Modern 1601-↗
PubMed1996

[ULUUS, the first Japanese medicine with a western name].

"ULUUS" is a patent medicine which was put on sale when the Japanese started to adopt Western Medicine brought in from Holland. It is regarded as the first medicine to have a Western-style name in Japan. In those days, ULUUS was thought be a useful medicine for patients with diseases called Tan, Ryuin and Shakki, causing the excretion of phlegm and bad accumulations in the body through expectoration, urine of feces. We recently obtained an ULUUS medication which was made in around 1870. It contains 15 tablets pressed neatly onto a sheet and has an inner wrapper, middle wrapper and outer wrapper made from 3 kinds of Japanese paper...

History, 19th Century↗
PubMed1996

[Chemical evaluation and consideration on the traditional drug "ULUUS" (1)].

Traditional medicine named "ULUUS" is regarded to be the first Dutch precipation with a western name in Japan. It was found that this drug consists of Rhubarb (originated from Rheum sp.). Although it is still uncertain whether it was made only of Rhubarb by being kneaded hard into the monotonous square form, we could not find out any other ingredients except Rhubarb, on the bases of our chemical analysis.

History, 20th Century↗
PubMed1995

Requirements for iron-regulated degradation of the RNA binding protein, iron regulatory protein 2.

Iron regulatory proteins (IRPs) regulate the expression of genes involved in iron metabolism whose transcripts contain RNA stem-loop motifs known as iron-responsive elements (IREs). When iron concentrations are low, IRPs bind to IREs in the 5' untranslated region (UTR) of transcripts where they repress translation, or the 3' UTR of transcripts where they inhibit degradation. The RNA binding activities of the homologous proteins IRP1 and IRP2 are both regulated post-translationally. The binding activity of IRP2 is regulated by the degradation of the protein when cells are iron-replete. Here, we demonstrate that a 73 amino acid sequence that corresponds to a unique exon in IRP2 contains a sequence required for rapid degradation in iron-replete cells. The deletion of this sequence eliminates the rapid turnover of IRP2, whereas the transfer of this sequence to the corresponding position in the homologous protein IRP1 confers the capacity for iron-dependent degradation upon IRP1. Site-directed mutagenesis has demonstrated that specific cysteines within the IRP2 exon are required for iron-dependent degradation. The degradation of IRP2 appears to be mediated by the proteasome in iron-replete cells. When degradation is prevented, the RNA binding activity of IRP2 is not regulated by iron concentration. Thus, degradation is required for the regulation of the RNA binding activity of IRP2.

Amino Acid Sequence↗
PubMed1995

Expression of a constitutive mutant of iron regulatory protein 1 abolishes iron homeostasis in mammalian cells.

Iron regulatory proteins (IRPs) are iron-sensing proteins that bind to RNA stem-loop sequences known as iron-responsive elements (IREs) when cells are depleted of iron. Although IRPs have been shown to bind to IREs derived from ferritin and transferrin receptor (TfR) mRNAs in vitro, there has not been a direct demonstration of the impact of a recombinant IRP on the expression of endogenous IRE-containing transcripts. In this study, we evaluate the impact of expression of C437S, a mutant of IRP1 that binds IREs regardless of cellular iron status, on the regulation of biosynthesis of ferritin and TfR. Despite being made iron-replete, cells expressing C437S continue to synthesize and express high amounts of TfR, while the synthesis of ferritin is repressed. Thus, a single mutant IRP can prevent the usual homeostatic changes in ferritin and TfR biosynthesis. Cells expressing the mutant protein would therefore be predicted to be unable to defend against iron overload. Preliminary results show that cells treated with iron have diminished cell survival when C437S is expressed, and we have thus created a tissue culture model system for the study of iron toxicity.

Ferritins↗