Biomedical subjects

M Hirai

Publications and source records attributed to M Hirai.

At least 55 records · Page 3Linked to original sources

PubMed2001

Quantitative expression studies of aldolase A, B and C genes in developing embryos and adult tissues of Xenopus laevis.

We previously cloned cDNAs for all the members (A, B and C) of Xenopus aldolase gene family, and using in vitro transcribed RNAs as references, performed quantitative studies of the expression of three aldolase mRNAs in embryos and adult tissues. A Xenopus egg contains ca. 60 pg aldolase A mRNA and ca. 45 pg aldolase C mRNA, but contains only ca. 1.5 pg aldolase B mRNA. The percent composition of three aldolase mRNAs (A:B:C) changes from 56:1.5:42.5 (fertilized egg) to 54:10:36 (gastrula), to 71:14.5:14.5 (neurula) and to 73:20:7 (tadpole) during development. These results are compatible with the previous results of zymogram analysis that aldolases A and C are the major aldolases in early embryos, whose development proceeds depending on yolk as the only energy source. Aldolase B mRNA is expressed only late in development in tissues such as pronephros, liver rudiment and proctodeum which are necessary for the future dietary fructose metabolism, and the expression pattern is consistent to that in adult tissues. We also show that three aldolase genes are localized on different chromosomes as single copy genes.

Animals↗

PubMed2001

MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects.

PURPOSE: To evaluate the MDR1 genotype frequency in the Japanese population and to study the relationship between the MDR1 genotype and the pharmacokinetics of digoxin after single oral administration in healthy subjects. METHODS: The MDR1 genotype at exon 26 was determined in 114 healthy volunteers by polymerase chain reaction-restriction fragment length polymorphism. The serum concentration-time profile of digoxin was examined after single oral administration at a dose of 0.25 mg. RESULTS: It was found that 35.1 % (40/114) of subjects were homozygous for the wild-type allele (C/C). 52.6% (60/114) were compound heterozygotes with a mutant T-allele (C3435T) (C/T), and 12.3% (14/114) were homozygous for the mutant allele (T/T). There was no effect of gender or age on the distribution. The serum concentration of digoxin after a single oral administration increased rapidly, attaining a steady state in all subjects; however, it was lower in the subjects harboring the T-allele. AUC0-4 h values (+/-SD) were 4.11 +/- 0.57, 3.20 +/- 0.49. and 3.27 +/- 0.58 ng h/ml, respectively, with a significant difference between C/C and C/T or T/T. CONCLUSIONS: The serum concentration of digoxin after single oral administration was lower in the subjects harboring a mutant allele (C3435T) at exon 26 of the MDR1 gene.

Adult↗

PubMed2001

Ex vivo purging by adenoviral p53 gene therapy does not affect NOD-SCID repopulating activity of human CD34+ cells.

Co-incubation of a replication-deficient, recombinant adenovirus carrying the wild-type p53 gene (rAd-p53) and hematopoietic stem cell (HSC) products from patients with breast cancer can significantly reduce tumor cell contamination. Whereas this approach provides a powerful tumor cell purging strategy, potential detrimental effects on the HSC population have not been investigated. The ability of human HSC to reconstitute hematopoiesis in severe combined immunodeficient (SCID) mice and to undergo secondary transplantation provides the only nonclinical measure of self-renewing, stem cell function. The objective of this study was to investigate whether co-incubation with rAd-p53 compromised the SCID repopulating activity (SRA) of HSC. Granulocyte colony-stimulating factor-mobilized human CD34+ cells were co-cultured with rAd-p53 at our targeted clinical dose, and the ability of these cells to establish multilineage hematopoiesis in sublethally irradiated, nonobese diabetic (NOD)-SCID mice was investigated. The persistence of human cells in the mice was investigated by flow cytometry, granulocyte-macrophage colony-forming unit assay, and polymerase chain reaction of human Alu sequences. Further, limiting dilution analysis provided a quantitative comparison between the SRA of CD34+ cells co-incubated with rAd-p53 and control CD34+ cells (no rAd-p53 co-incubation). We conclude that co-incubation with rAd-p53 has little effect on the SRA of HSC.

Adenoviridae↗

PubMed2001

The juvenile hormone binding protein of silkworm haemolymph: gene and functional analysis.

A cDNA fragment of haemolymph juvenile hormone binding protein (hJHBP) from larvae of Bombyx mori was amplified by RT-PCR using degenerate primers based on the N-terminal amino acid sequence of purified hJHBP and a conserved region near the C-terminus of other lepidopteran hJHBPs. 5'- and 3'-ends were amplified by RACE to yield cDNAs, hJHBP1 and hJHBP2, encoding 225 amino acids with three substitutions. hJHBP-mRNA levels in the fat body were constant in the 4th instar, but decreased in the 5th. JHBP protein was constant until wandering, then declined. Recombinant hJHBP1 expressed in E. coli migrated on SDS-PAGE with a Mr of 32 kDa and showed a Kd of 4.5 x 10-7 M with JH III, both similar to those of native hJHBP.

Amino Acid Sequence↗

PubMed2001

Prolongation of activation-recovery interval over a preexcited region before and after catheter ablation in patients with Wolff-Parkinson-White syndrome.

INTRODUCTION: Preexisting changes in repolarization properties play an important role in T wave abnormalities (cardiac memory) after ablation in patients with Wolff-Parkinson-White (WPW) syndrome. However, no report has provided direct evidence for prolongation of action potential duration (APD) over a preexcited region before and after ablation. METHODS AND RESULTS: We studied 10 patients with ventricular preexcitation due to a left-sided accessory pathway (AP) (group M) and 12 patients with concealed left-sided AP (group C) to clarify prolongation of APD using activation-recovery intervals (ARIs) from epicardial and endocardial unipolar electrograms in patients with WPW syndrome. ARI was calculated from unipolar electrograms at the His bundle and the coronary sinus adjacent to the AP during atrial pacing (100 beats/min) before and 30 minutes after ablation. Before ablation, ARIs at the AP site were significantly longer in group M than in group C (255+/-21 msec vs 211+/-24 msec; P < 0.01), whereas ARIs at the His bundle did not differ between the two groups (255+/-20 msec vs 245+/-27 msec; P = NS). After ablation, group M showed no significant changes in ARIs at the AP and His bundle (256+/-19 msec and 253+/-15 msec) compared with before ablation. CONCLUSION: We found by direct analysis of ARIs from the epicardium that APD prolongation over the preexcited region was present before catheter ablation and persisted after catheter ablation. The gradual changes in repolarization properties, including APD prolongation after discontinuation of AP, may be one mechanism of cardiac memory after catheter ablation in patients with WPW syndrome.

Action Potentials↗

PubMed2001

Papillary carcinoma of the thyroid with distant metastases to the cerebrum: a case report.

Cerebral metastases from papillary carcinoma of the thyroid are a very uncommon condition, but such metastases behave more aggressively and show poor prognosis. These metastases almost always involve concomitant lung or bone metastases which may be the first metastatic sites. Here we report a 53-year-old man with diffuse goiter and cervical lymphadenopathy who developed symptoms of elevated intracranial pressure. Computed tomography demonstrated ring-enhanced lesions showing a severe mass effect in the right cerebrum and a nodule in the right thyroid gland accompanied by swollen lymph nodes. Biopsied specimens of the thyroid nodule demonstrated malignant cells of papillary carcinoma. Surgical excision of the metastatic brain lesions was followed by total thyroidectomy with regional lymphadenectomy. Histological examinations confirmed that the patient had cerebral metastases from papillary carcinoma of the thyroid without other distant metastasis. Neurological abnormality disappeared after surgery and treatment with radioactive iodine (131I) and oral thyroxine were initiated thereafter. This case suggests that the thyroid gland is potentially a primary source of metastatic brain carcinoma. Moreover, early detection of cerebral metastases is crucial because these metastatic lesions can be life threatening, in contrast to the relatively less severe clinical course of this malignancy unless it is associated with any distant metastasis.

Brain Neoplasms↗

PubMed2001

Chitosan induces apoptosis via caspase-3 activation in bladder tumor cells.

Recently, because of its low toxicity and biological effects, chitosan has been widely used in the medical and pharmaceutical fields, e.g., for nasal or oral delivery of peptide or polar drug delivery. Here, we report a growth-inhibitory effect of chitosan on tumor cells. The growth inhibition was examined by WST-1 colorimetric assay and cell counting. We also observed DNA fragmentation, which is characteristic of apoptosis, and elevated caspase-3-like activity in chitosan-treated cancer cells. The findings suggest that chitosan may have potential value in cancer therapy.

Antineoplastic Agents↗

PubMed2001

Molecular cloning of a human novel type I cytokine receptor related to delta1/TSLPR.

In a search for a human sequence related to a recently identified type I cytokine receptor delta1, which turned out to be a receptor subunit for a cytokine called TSLP, we have now identified a novel human type I cytokine receptor from a human T lymphocyte cDNA library. The deduced amino acid sequence of 371 residues has a typical signal sequence and a membrane-spanning region. The mature protein is predicted to have a molecular mass of 39,698 Da. The N-terminal extracellular region contains two fibronectin type III-like domains, four conserved cysteine residues, and a WSXWS box-like motif. The C-terminal intracellular region contains box 1 and box 2-like motifs. Thus, it has common characteristics of type I cytokine receptor family members, and we tentatively termed this protein CRLF2, which stands for cytokine receptor-like factor 2. Northern blot analysis revealed CRLF2 mRNA in liver, kidney, heart, and skeletal muscle. The fetal liver also expresses CRLF2 transcripts. The gene for CRLF2 was mapped to the pseudoautosomal region, Xp22.3 and Yp11.3 by FISH analysis, a region where genes encoding the IL-3 receptor alpha and the GM-CSF receptor alpha chains are also located. The biological function of this newly identified receptor is now under investigation.

Amino Acid Motifs↗

PubMed2001

Reversal effects of antifungal drugs on multidrug resistance in MDR1-overexpressing HeLa cells.

In this study, the antiproliferative effects of vinblastine (VLB), paclitaxel (TXL), doxorubicin (DXR), daunorubicin (DNR) and 5-fluorouracil (5-FU) were assessed in the human cervical carcinoma cell line HeLa-Ohio (HeLa) and Hvr100-6 cells, established by growing the parental HeLa cells in the presence of progressively greater concentrations of VLB in the culture medium. Flow cytometric analysis indicated the induction of MDR1 (P-glycoprotein) in Hvr100-6 cells with no alterations in levels of multidrug resistance-associated protein (MRP). Resistance to VLB, TXL, DXR and DNR was found in Hvr100-6 cells with relative resistances of ca. 300, 4000, 50 and 200, respectively, whereas no resistance was found to 5-FU. The reversal effects of antifungal drugs, fluconazole, itraconazole, ketoconazole, miconazole and amphotericin B on multidrug resistance were also assessed using Hvr100-6 cells. Itraconazole was found to have potent reversal effect on the resistance to VLB and TXL, but the others had no such effect. This reversal effect of itraconazole was concentration-dependent, with dose modifying factors of 3.2, 10.1 and 435.7 at 0.1, 0.25 and 0.5 microM of itraconazole, respectively. In addition, this reversal effect of itraconazole was explained by the inhibition of accumulation of the anticancer drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Effect of serum triglyceride concentration on the fluctuation of whole blood concentration of cyclosporin A in patients.

The methodology to distinguish the patients showing considerable fluctuation of the whole blood concentration of cyclosporin A (CYA) was investigated from a viewpoint of laboratory test values. First, we retrospectively examined the CYA trough blood concentrations monitored continuously. The patients were classified into three groups by the fluctuation of CYA trough blood concentrations during the examination period (Cmax/Cmin): Group 1 (Cmax/Cmin=100-200%; n=21), Group 2 (Cmax/Cmin=200-300%; n=25), and Group 3 (Cmax/Cmin=more than 300%; n=32). In the laboratory tests examined, the serum triglyceride concentrations were considerably different among the groups, and it was the highest in Group 3. Next, to elucidate the effect of serum triglyceride concentration on the CYA blood concentration, in vivo pharmacokinetic studies after single intravenous or repetitive oral administration of CYA were conducted in the model rats with pseudo-hypertriglyceridemia, hypocythemia, and acute renal failure. Only in pseudo-hypertriglyceridemia rats, the CYA blood concentration after a single intravenous injection was significantly higher than that in normal rats because of the restriction of CYA distribution to the extravascular tissues. On the other hand, the increase in the serum triglyceride concentration did not affect the fluctuation of CYA trough blood concentration after repetitive oral administration. Taken together, the fluctuation of CYA trough blood concentrations observed in the clinical situation could be due to the fluctuation of serum triglyceride concentration, and the patients with such fluctuation of serum triglyceride concentrations might also be distinguishable by the higher concentration of serum triglyceride in laboratory tests.

Acute Kidney Injury↗

PubMed2001

Activation-recovery intervals of 12-lead electrocardiograms before and after catheter ablation in patients with Wolff-Parkinson-White syndrome.

Preexcitation in Wolff-Parkinson-White syndrome (WPW) has been reported to induce long-lasting changes in ventricular recovery properties. However, there has not been a report concerning changes in the activation-recovery interval (ARI) in 12-lead ECGs before and after catheter ablation (CA) in patients with WPW syndrome. The present study compared changes in ARIs from 12-lead ECGs with those from body surface unipolar leads before and after CA to examine whether ARIs from limb leads of 12-lead ECGs provide useful information on changes in recovery properties in addition to the ARIs from precordial leads. The study population consisted of 27 manifest WPW patients with a left- (n=18, group A) or right-sided accessory pathway (n=9, group B). ARIs in leads I, II, and III were strongly correlated with those in unipolar leads over the left lateral, left lower, and right lower chest, respectively. ARIs in leads aVR, aVL, and aVF showed a significant correlation with those in unipolar leads over the right upper, left upper, and lower anterior chest, respectively. These correlations were maintained before and after CA. Furthermore, in group A, ARIs in lead V1 tended to increase on day 7 post CA compared with before CA and on day 1. In group B, ARIs in lead III significantly decreased on day 7 compared with before CA and on day 1. These findings suggest that ARIs from the limb leads of 12-lead ECGs may represent those from unipolar leads of a particular area over the body surface, and that ARIs from 12-lead ECGs may provide useful quantitative information on changes in recovery properties before and after CA in patients with manifest WPW syndrome.

Adolescent↗

PubMed2001

Histopathologic evaluation of coronary artery thrombi obtained by directional coronary atherectomy in patients with restenosis-induced unstable angina pectoris.

The pathogenesis of unstable angina pectoris (UAP) following percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy (DCA) has not been adequately investigated, so the present study aimed to determine whether thrombi are present in restenotic lesions. The study group comprised 14 patients (16 arterial branches) with angina pectoris in whom either PTCA or DCA was performed and who had developed UAP associated with restenosis, and who then underwent DCA of the restenosed lesion (R-UAP group). The control groups comprised individuals with UAP undergoing DCA with no prior history of PTCA or DCA (P-UAP group; n=29, 29 branches), patients with acute myocardial infarction (AMI group; n=34, 34 branches), and patients with stable angina pectoris (SAP group; n=31, 33 branches). The presence of thrombi was determined by light microscopy of histologic specimens. Thrombus was present in only 1 of the 16 (6.3%) branches in the R-UAP group. 21 of the 29 (72.4%) branches in the P-UAP group, and in 25 of the 34 (73.5%) in the AMI group. In the SAP group, it was detected in only 2 of the 33 (7.1%) branches. The incidence of thrombus was significantly lower in the R-UAP group than in the P-UAP group. In conclusion, the role of thrombus is limited in causing post-interventional UAP at restenosed sites.

Aged↗

PubMed2001

Differential effects of hypoxia and hypercapnia on respiratory sinus arrhythmia in conscious dogs.

To test the hypothesis that hypoxia and hypercapnia have different effects on the genesis of respiratory sinus arrhythmia (RSA), the magnitude of RSA to these stimuli was compared in 3 unanesthetized dogs. Respiration was continuously monitored through a permanent tracheostomy, and the electrocardiogram and blood pressure were also monitored. The magnitude of RSA was assessed as an instantaneous amplitude of the R-R interval oscillation in the high-frequency band of 0.15-0.80Hz by means of complex demodulation. In a total of 47 runs with hypoxia, heart rate, mean arterial pressure, respiratory rate and tidal volume increased, but RSA magnitude decreased even after adjusting for the effects of respiratory rate and tidal volume. In a total of 39 runs with hypercapnia, heart rate and mean arterial pressure did not change, despite the increased respiratory rate and tidal volume. In contrast to hypoxia, RSA magnitude increased even after adjusting for the effects of respiratory rate and tidal volume. The different effects of the two respiratory stimuli on RSA magnitude were noted at any level of ventilation and support the original hypothesis.

Animals↗

PubMed2001

Comparison of the biological H2S removal characteristics among four inorganic packing materials.

Four inorganic packing materials were evaluated in terms of their availability as packing materials of a packed tower deodorization apparatus (biofilter) from the viewpoints of biological H2S removal characteristics and some physical properties. Among porous ceramics (A), calcinated cristobalite (B), calcinated and formed obsidian (C), granulated and calcinated soil (D), the superiority of these packing materials determined based on the values of non-biological removal per unit weight or unit volume of packing material, complete removal capacity of H2S per unit weight of packing material per day or unit volume of packing material per day and pressure drop of the packed bed was in the order of A approximately equal to C > D approximately equal to B, which is correlated with the maximum water content, porosity, and mean pore diameter.

Journal Article↗

PubMed2001

Comparison of the biological NH3 removal characteristics among four inorganic packing materials.

Four inorganic packing materials were evaluated in terms of their availability as a packing material of a packed tower deodorization apparatus (biofilter) from the viewpoints of biological NH3 removal characteristics and some physical properties. Porous ceramics (A), calcinated cristobalite (B), calcinated and formed obsidian (C), granulated and calculated soil (D) were used. The superiority of these packing materials determined based on the values of non-biological removal per unit weight or unit volume of packing material, complete removal capacity of NH3 per unit weight of packing material per day or unit volume of packing material per day and pressure drop of the packed bed was in the order of A approximately = C > B > or = D. Packing materials A and C with high porosity, maximum water content, and suitable mean pore diameter showed excellent removal capacity.

Journal Article↗

PubMed2001

Molecular cloning and characterization of human Frizzled-8 gene on chromosome 10p11.2.

Mouse Frizzled-8, encoding a WNT receptor, is a potent cancer-associated gene to activate the beta-catenin-TCF pathway. However, these is a possibility that mouse Frizzled-8 might be a pseudogene, because structure and expression profile of mouse Frizzled-8 mRNA are still unclear. We have cloned and characterized the human Frizzled-8 (FZD8) gene, a human homologue of mouse Frizzled-8. Comparison between FZD8 genome clones and FZD8 cDNA clones isolated in this study revealed no intron within the FZD8 gene. FZD8 was found to encode a 694 amino-acid polypeptide with the frizzled-like cysteine-rich domain, seven transmembrane domains, and the C-terminal Ser/Thr-X-Val motif. Among human FZD family, FZD8 was most homologous to FZD5 (total amino-acid identity 69.1%). The 4.0-kb FZD8 mRNA was detected in fetal kidney and brain, and also in adult kidney, heart, pancreas, and skeletal muscle. These results indicate that human FZD8 is not a pseudogene. The FZD8 gene was mapped to human chromosome 10p11.2 by fluorescence in situ hybridization. Among human cancer cell lines, FZD8 was relatively highly expressed in HeLa S3 (cervical uterus cancer) and A549 (lung cancer). Up-regulation of FZD8 might play key roles in several types of human cancer through activation of the beta-catenin-TCF pathway.

Amino Acid Sequence↗

PubMed2001

Molecular cloning and characterization of human Frizzled-5 gene on chromosome 2q33.3-q34 region.

Hfz5 is a potent cancer associated gene, encoding WNT receptor with the potential to activate beta-catenin - TCF signaling pathway. Here, human Frizzled-5 (FZD5) gene and cDNAs were cloned and characterized. FZD5 was almost identical to Hfz5, except for six amino-acid substitutions at codon 88, 262, 263, 345, 357, and 402. HF5S1 probe (nucleotide position 2036-2535 of FZD5 cDNA) hybridized to 7.5- and 3.5-kb FZD5 mRNAs, and HF5S2 probe (nucleotide position 5572-6194 of FZD5 cDNA) hybridized only to 7.5-kb FZD5 mRNA. FZD5 cDNA was polyadenylated at the nucleotide position 6534, while several FZD5 ESTs were polyadenylated at the nucleotide position 2561. The 7.5- and 3.5-kb FZD5 mRNAs were transcribed probably due to alternative splicing. FZD5 was highly expressed in fetal liver and adult pancreas, and moderately expressed in fetal lung, kidney and adult liver. Among human cancer cell lines, FZD5 was highly expressed in K-562 cells derived from chronic myelogenous leukemia. FZD5 gene, consisting of two exons, was mapped to human chromosome 2q33.3-q34 region, near the FZD7 gene and the FRA2I fragile site. These results suggest that FZD5 up-regulation might play key roles in chronic myelogenous leukemia through activation of the WNT - beta-catenin - TCF signaling pathway.

Amino Acid Sequence↗

PubMed2001

[Case report of a malignant schwannoma in the neck with rare pathological findings].

In this report, we describe a rare case of a malignant transformation in an ancient schwannoma arising in the right side of the neck of a 51-year-old man. The patient was referred to our hospital because of a mass that had been present for three years. The mass, measuring about 4 x 2 cm, was elastic and hard, relatively well demarcated, and movable upon palpation. Aspiration cytology was performed, but the diagnosis was unclear histologically. The patient was placed under general anesthesia and the tumor was totally excised. The tumor, which was easily excised, was connected to the sympathetic nerve at both poles. The histological diagnosis was a malignant transformation in an ancient schwannoma. The patient showed no clinical manifestations suggesting neurofibromatosis. Three months after the operation, a recurrent tumor, which was not resectable, was discovered extending deep into the skull base. The patient underwent two operations and two courses of radiation therapy, but the tumor metastasized to the lung and liver. He died of pulmonary failure eleven months after the initial treatment.

Head and Neck Neoplasms↗