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Biomedical subjects

Akira Ishiguro

Publications and source records attributed to Akira Ishiguro.

9 recordsLinked to original sources
PubMed2005

Neutrophil-mediated inflammation in respiratory syncytial viral bronchiolitis.

BACKGROUND: The involvement of neutrophil-mediated inflammation may play an important role in the pathogenesis of acute respiratory syncytial virus bronchiolitis. However, no measurable marker is sensitive enough to assess neutrophil-mediated inflammation in the airways. Released neutrophil elastase (NE) in intraluminal airways has been reported to induce pulmonary inflammation. The aim of this study was to determine whether the amount of urinary trypsin inhibitor (UTI) in serum, a degenerate induced by NE, reflects the degree of airway inflammation in children with respiratory syncytial viral (RSV) bronchiolitis and whether the severity of inflammation is evaluated. The pre-alpha-/inter-alpha-trypsin inhibitor is assumed to be precursors of the UTI. When NE degrades these inhibitors, UTI is liberated. METHODS: Serum UTI concentrations in infants admitted with RSV bronchiolitis, other viral infections, bacterial pneumonia and control subjects were measured by means of one-step sandwich-type enzyme immunoassay. RESULTS: Serum UTI concentrations in 25 patients on admission were significantly higher than the 15 infantile control values (mean +/- SEM, 22.126 +/- 2.317 and 6.701 +/- 0.719 U/mL, respectively; P < 0.0001). The elevated levels returned to baseline values with improvement in the respiratory symptoms. Higher levels of serum UTI with RSV infection were consistently associated with clinical symptoms and artificial ventilation. Serum NE concentrations of patients were elevated in some patients but not significantly different from controls in the patients who showed only upper respiratory symptoms with RSV infections. CONCLUSION: The findings strongly suggested that neutrophil-mediated events are involved in the pathogenesis of RSV bronchiolitis, and the monitoring of UTI concentrations might be useful for evaluating the neutrophil-mediated airway inflammation.

Bronchiolitis↗
PubMed2004

Molecular properties of Zic4 and Zic5 proteins: functional diversity within Zic family.

The Zic-family proteins control various developmental processes. Previous studies have shown that Zic1, Zic2, and Zic3 can act as transcriptional regulators, and that their functions are repressed by I-mfa, which has been identified as a repressor for basic helix-loop-helix-type transcriptional factors. Here, we investigated the molecular properties of the Zic4 and Zic5 proteins. Zic4/Zic5 showed DNA-binding activity to the Gli-binding sequence, similar to Zic1/Zic2/Zic3 proteins. However, Zic4/Zic5 did not exhibit any significant transcriptional activation ability nor they bind to I-mfa differently from Zic1/Zic2/Zic3. The nuclear localization of Zic4/Zic5 was not affected by the presence of the I-mfa protein, whereas the Zic1/Zic2/Zic3 proteins were translocated to the cytoplasmic compartment in the presence of I-mfa. The difference may be attributable to the dissimilarity of the N-terminal region between the Zic1/Zic2/Zic3 and Zic4/Zic5 proteins, since the binding of the Zic1/Zic2/Zic3 proteins to I-mfa occurs through their N-terminal regions.

Amino Acid Sequence↗
PubMed2003

Dorz1, a novel gene expressed in differentiating cerebellar granule neurons, is down-regulated in Zic1-deficient mouse.

The Zic1 gene encodes a zinc finger protein that controls vertebrate neural development. A previous study showed that Zic1 is expressed in developing and mature cerebellar granule neurons, and that Zic1-deficient cerebellum is hypoplastic and lacks a lobule of the anterior lobe. In the present study, we searched for genes de-regulated in the cerebellum to understand the molecular basis of cerebellar development. A novel gene, Dorz1, was identified and characterized as one of the most significantly down-regulated genes in Zic1-deficient cerebellum by the DNA microarray analysis. The expression of Dorz1 in the developing cerebellum peaked at embryonic day 17.5, and at that stage Dorz1 transcripts were detected in cerebellar granule neuron precursors where Zic1 expression is enhanced. In addition, Dorz1 expression was up-regulated in cultured cells overexpressing Zic1. These results suggest that Dorz1 expression is positively regulated by Zic1 during cerebellar development.

Aging↗
PubMed2003

A gene-specific effect of an internal deletion in the Bdp1 subunit of the RNA polymerase III transcription initiation factor TFIIIB.

The Saccharomyces cerevisiae RPR1 gene encodes the RNA subunit of its RNase P, which processes RNA polymerase (pol) III primary transcripts. RPR1, which is transcribed by pol III, has been isolated as a multicopy suppressor of a specific small internal deletion (amino acids 253-269) in the Bdp1 subunit of transcription factor TFIIIB, the core pol III transcription factor. The selective effect of this Bdp1 deletion on RPR1 transcription has been analyzed in vitro. It is shown that TFIIIC-dependent assembly of TFIIIB on the RPR1 promoter is specifically sensitive to this Bdp1 deletion, leading to gene-specifically defective single-round and multiple-round transcription.

Base Sequence↗
PubMed2003

The fission yeast RPA51 is a functional homolog of the budding yeast A49 subunit of RNA polymerase I and required for maximizing transcription of ribosomal DNA.

Saccharomyces cerevisiae A49 and mouse PAF53 are subunits specific to RNA polymerase I (Pol I) in eukaryotes. It has been known that Pol I without A49 or PAF53 maintains non-specific transcription activities but a molecular role(s) of A49 (and PAF53) remains totally unknown. We studied the fission yeast gene encoding a protein of 415 amino acids exhibiting 30% and 19% identities to A49 and PAF53, respectively. We designate the corresponding protein RPA51 and gene encoding it rpa51+ since the gene encodes a Pol I subunit and an apparent molecular mass of the protein is 51 kDa. rpa51+ is required for cell growth at lower but not at higher temperatures and is able to complement S. cerevisiae rpa49Delta mutation, indicating that RPA51 is a functionally-conserved subunit of Pol I between the budding yeast and the fission yeast. Deletion analysis of rpa51+ shows that only two-thirds of the C-terminal region are required for the function. Transcripts analysis in vivo and in vitro shows that RPA51 plays a general role for maximizing transcription of rDNA whereas it is dispensable for non-specific transcription. We also found that RPA51 associates significantly with Pol I in the stationary phase, suggesting that Pol I inactivation in the stationary phase of yeast does not result from the RPA51 dissociation.

Amino Acid Sequence↗
PubMed2002

Elevation of serum thrombopoietin precedes thrombocytosis in acute infections.

To clarify the mechanisms underlying thrombocytosis secondary to infections, we longitudinally studied serum levels of thrombopoietin (TPO) and interleukin (IL)-6 in 15 infants and young children with prominent thrombocytosis (platelets >700 x 10(9)/l) following acute infections and 116 age-matched controls using an enzyme-linked immunosorbent assay. The subjects included nine patients with bacterial infections, three with viral infections and three with non-determined pathogens. TPO values in the controls were 2.24 +/- 0.87 fmol/ml (mean +/- SD) with a 95% reference interval of 0.85-4.47 fmol/ml. In the first week of infection, platelet counts were normal, but TPO values increased (approximately 10.73 fmol/ml). TPO levels peaked on day 4 +/- 2 at 6.44 +/- 2.37 fmol/ml and then fell gradually. When platelet counts peaked in the second and third weeks, TPO levels were similar to the controls. IL-6 levels in the first week rose and dropped more rapidly than TPO. Serum TPO values were significantly correlated with C-reactive protein levels (r = 0.688, P < 0.001) and IL-6 levels (r = 0.481, P = 0.027). These results suggest that TPO contributes to thrombocytosis following infections in conjunction with IL-6, arguing for additional regulatory mechanisms of blood TPO levels.

Acute Disease↗
PubMed2002

Essential roles of Bdp1, a subunit of RNA polymerase III initiation factor TFIIIB, in transcription and tRNA processing.

The essential Saccharomyces cerevisiae gene BDP1 encodes a subunit of RNA polymerase III (Pol III) transcription factor (TFIIIB); TATA box binding protein (TBP) and Brf1 are the other subunits of this three-protein complex. Deletion analysis defined three segments of Bdp1 that are essential for viability. A central segment, comprising amino acids 327 to 353, was found to be dispensable, and cells making Bdp1 that was split within this segment, at amino acid 352, are viable. Suppression of bdp1 conditional viability by overexpressing SPT15 and BRF1 identified functional interactions of specific Bdp1 segments with TBP and Brf1, respectively. A Bdp1 deletion near essential segment I was synthetically lethal with overexpression of PCF1-1, a dominant gain-of-function mutation in the second tetracopeptide repeat motif (out of 11) of the Tfc4 (tau(131)) subunit of TFIIIC. The analysis also identifies a connection between Bdp1 and posttranscriptional processing of Pol III transcripts. Yeast genomic library screening identified RPR1 as the specific overexpression suppressor of very slow growth at 37 degrees C due to deletion of Bdp1 amino acids 253 to 269. RPR1 RNA, a Pol III transcript, is the RNA subunit of RNase P, which trims pre-tRNA transcript 5' ends. Maturation of tRNA was found to be aberrant in bdp1-Delta 253-269 cells, and RPR1 transcription with the highly resolved Pol III transcription system in vitro was also diminished when recombinant Bdp1 Delta 253-269 replaced wild-type Bdp1. Physical interaction of RNase P with Bdp1 was demonstrated by coimmunoprecipitation and pull-down assays.

Amino Acid Sequence↗
PubMedDate not supplied

Age dependence of diffusion-weighted magnetic resonance imaging findings in maple syrup urine disease encephalopathy.

A patient with maple syrup urine disease (MSUD) who developed encephalopathy twice and underwent magnetic resonance examinations, including diffusion-weighted (DW) imaging, is presented. Areas of abnormal intensity on DW images dramatically differed between the initial and second attacks, apparently attributable to the difference in myelination. Our observation demonstrates the age dependence of DW imaging findings in MSUD encephalopathy attributable to progression of myelination and would help in the proper diagnosis of MSUD encephalopathy at any age.

Age Factors↗