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Biomedical subjects

M Hirai

Publications and source records attributed to M Hirai.

At least 127 records · Page 7Linked to original sources
PubMed1999

Inverse relation of body-surface activation-recovery interval and recovery time to activation time in normal subjects: stronger correlation and more heterogeneous distribution in activation-recovery interval than in recovery time.

The activation-recovery interval (ARI), measured directly from the myocardium, has shown a good correlation with the action potential duration (APD) in experiments. APD has been reported to be inversely related to the activation time (AT). However, no studies have examined the correlation between the body-surface ARI and AT in normal subjects. Fifty normal subjects (25 men and 25 women) were studied to elucidate the relationship between the body-surface ARI and AT. The body-surface AT was defined as the duration between the QRS onset and the minimum dV/dt of the QRS wave, and ARI as the interval between the minimum dV/dt of the QRS wave and the maximum dV/dt of the T wave in each lead of an 87 unipolar lead system. We also measured the recovery time (RT) defined as the duration between the QRS onset and the maximum dV/dt of the T wave. ARI was inversely correlated with AT (r = -0.73). RT was also inversely correlated with AT (r = -0.61), however, RT had a less heterogeneous distribution than ARI (148 ms vs 159 ms). There were no differences between male and female subjects in the relation between ARI and RT or in the body-surface distribution of ARI and RT. These findings suggest that the body-surface ARI may reflect recovery properties over the cardiac surface and that APD may distribute inhomogeneously over the human cardiac surface with a longer RT over an area with a shorter AT. ARI calculated from body-surface ECG may be a useful noninvasive and repeatedly measurable estimate of APD.

Adolescent↗
PubMed1999

The genes degQ, pps, and lpa-8 (sfp) are responsible for conversion of Bacillus subtilis 168 to plipastatin production.

Bacillus subtilis YB8 produces the lipopeptide antibiotic plipastatin. B. subtilis MI113, which is a derivative of strain 168, was converted into a new plipastatin producer, strain 406, by competence transformation with the chromosomal DNA of YB8. Transposon mini-Tn10 insertional mutagenesis was applied to strain 406, which revealed that lpa-8 (sfp) (encoding 4'-phosphopantetheinyl transferase) and the pps operon (located between 167 and 171 degrees ) are essential for plipastatin production. The pps operon was previously suggested to encode putative peptide synthetases (A. Tognoni, E. Franchi, C. Magistrelli, E. Colombo, P. Cosmina, and G. Grandi, Microbiology 141:645-648, 1995) and was thought to be the fengycin operon (V. Tosato, A. M. Albertini, M. Zotti, S. Sonda, and C. V. Bruschi, Microbiology 143:3443-3450, 1997). We claim that the pps operon is the pli operon, encoding plipastatin synthetase. By using a new high-performance liquid chromatography system, we revealed that strain 168 expressing only lpa-8 can also produce plipastatin, although the yield is very low. However, the introduction of the pleiotropic regulator degQ of strain YB8 into strain 168 expressing lpa-8 resulted in a 10-fold increase in the production of plipastatin.

Bacillus subtilis↗
PubMed1999

Genomic structure and chromosome location of RPL27A/Rpl27a, the genes encoding human and mouse ribosomal protein L27A.

The intron-containing genes encoding human and mouse ribosomal protein (r-protein) L27A were cloned and sequenced. The human r-protein L27A gene (RPL27A) shared an identical exon/intron structure with the mouse r-protein 27A gene (Rpl27a). The translational start codon ATG was separated from the main reading frame by the first intron sequence in both genes. An approximately 200-bp sequence upstream of the translational start site of both genes displayed remarkable similarity, and contained the putative promoters lacking canonical TATA, but harbored Sp1 binding sites and a short stretch of pyrimidine cluster, similar to other r-protein genes. Transcriptional regulatory elements, Box-A and GABP, found in the promoters of some other r-protein genes were also conserved in both genes. These structural features were included in the typical CpG island identified in the 5'-end sequences, suggesting that RPL27A/Rpl27a cloned here are authentic and transcriptionally active. Fluorescence in situ hybridization (FISH) analysis localized the mouse intron-containing Rpl27a to chromosome 7E2-F1 syntenic to human chromosome 11p15, where human RPL27A was located.

Animals↗
PubMed1999

Adenovirus p53 purging for human breast cancer stem cell products.

Tumor cell (TC) contamination of stem cell products can contribute to relapse after high dose chemotherapy and stem cell rescue. A new purging technology using replication-deficient recombinant adenovirus (Adv) containing the p53 tumor suppressor gene (Adv-p53) has been suggested to reduce tumor contamination of autologous stem cell product. We demonstrate herein a safe and effective Adv-p53 purging procedure using four human breast cancer TC lines. Multiple parameters need to be achieved to successfully purge stem cell products, including a high cell:virus ratio, a small incubation volume, a long incubation time and 37 degrees C rather than room temperature. These parameters are all interrelated and equally important for the inhibition of TC clonogenic growth. In our studies, we also observed that Adv could nonspecifically inhibit TC clonogenic growth, although Adv-p53 treatment led to a significantly greater inhibition of clonogenic growth by cells expressing mutated p53. The presence of peripheral stem cell (PSC) products was found to decrease the effect of Adv-p53 on TC clonogenic growth, suggesting that PSC products could compete with TC for infection by recombinant Adv. However, X-Gal staining after incubation with Adv containing-galactosidase demonstrated that PSC products were 2, 000-fold more resistant to Adv infection than TC. We conclude that a 4-hour incubation of stem cell products (2 x 10(8)/ml) with 4 x 10(11) Adv-p53 particles is sufficient to completely purge TC with no effect on hematopoietic cell function.

Adenoviridae↗
PubMed1999

Effect of age on urinary excretion of N-acetyl-beta-D-glucosaminidase.

To examine the relationship between the concentrations of urinary NAG and age, we measured ratios of urinary N-acetyl-beta-D-glucosaminidase (NAG) to urinary creatinine (NAG index) in 137 healthy subjects, aged from 19 to 88 years. The study is also designed to evaluate the relationship between urinary NAG and blood pressure. The subjects were divided into 7 subgroups, according to their age (< 30, 30-39, 40-49, 50-59, 60-69, 70-79, 80 or more years). There was a positive correlation between NAG index and age (r = 0.36; P < 0.001). The regression equation relating NAG index (y) to age (x) was y = 0.065x + 0.97. The mean NAG indexes for the 7 subgroups divided by age were significantly different (P < 0.01). There was a positive correlation between NAG index and systolic blood pressure (r = 0.18; P < 0.05), but was not between diastolic blood pressure and NAG index. In multiple regression analysis, age and BUN significantly correlated with NAG index (r = 0.32; P < 0.01, r = 3.3; P = 0.07, respectively), although there was no correlation between systolic blood pressure and NAG index. This cross-sectional study showed a clear elevation in NAG index with age. The rate of elevation was 0.65 per decade. Urinary excretion of NAG may be unrelated to blood pressure.

Acetylglucosaminidase↗
PubMed1999

[A case of esophageal cancer with excellent response to oral UFT treatment].

The patient was an 83-year-old Japanese male with the chief complaint of difficulty in swallowing. On Feb. 24, 1997, he was referred to our hospital under suspicion of esophageal cancer. X-P revealed an image of a protrusion at Im-Iu having a long diameter of 6 cm. Endoscopy revealed that the esophageal lumen was nearly completely obstructed due to the presence of an irregularly-shaped tumor. The pathological finding of biopsized specimen was a squamous cell carcinoma. Thus, this case was diagnosed as esophageal cancer, but surgery was deemed inappropriate due to the patient's advanced age. Accordingly, on March 12, treatment was started with oral administration of UFT-E granules (Tegafur, 450 mg/day). Initially, the patient was unable to ingest even liquids, but beginning around May the blockage of the esophagus disappeared. Endoscopic examination performed in June revealed that the tumor had shrunk to a about 1 cm in diameter. Although tumor tissue remained, the tumor was observed to have undergone further reduction in size at 6 months after the start of chemotherapy. Moreover, the patient gained weight. This is considered to be a very rare case of an excellent response of esophageal cancer to oral administration of only UFT agents.

Administration, Oral↗
PubMed1999

[A case report of concomitant operation of minimally invasive direct coronary artery bypass and left lower lobectomy].

A 72-year-old man was admitted complaining of laryngeal discomfort. A coronary angiogram showed a total occlusion of the LAD, a 90% stenosis of the 1st diagonal branch and well-developed collaterals from the LCX to the LAD. A chest X-ray showed a consolidation with unclear border at the left hilus of the lung. A lung biopsy through the bronchus revealed an adenocarcinoma of the left lower lung. He underwent a concomitant CABG operation without a cardiopulmonary bypass and a left lower lobectomy with lymph node dissection. The CABG was performed by left anterior small thoracotomy in the supine position and the lobectomy was performed by left posterolateral thoracotomy in the right lateral position. An intraoperative postural conversion was useful to obtain a good field in each operation and to prevent hemodynamic deterioration due to heart compression.

Adenocarcinoma↗
PubMed1999

Gains of 1q21-q22 and 13q12-q14 are potential indicators for resistance to cisplatin-based chemotherapy in ovarian cancer patients.

The mechanism of drug resistance in ovarian cancer is multifactorial, and accumulation of multiple genetic changes may lead to the drug-resistant phenotype. In our attempt to find characteristic genetic changes in drug-resistant tumors, we screened the whole genome for gene aberrations in 28 primary ovarian cancers using the comparative genomic hybridization method. These cancers included 14 tumors from patients who did not respond to cisplatin-based combination chemotherapy and 14 tumors from patients who had complete response to the chemotherapy. We found gains in chromosomal regions 1q21-q22 and 13q12-q14 to be related to the drug-resistant phenotype in ovarian cancer patients. Several genes encoding transcription factors, oncogenes, cell cycle regulators, and regulators of the apoptotic pathway are located on these regions of the chromosomes, and these genes are potential modulators for toxic insults in cancer cells. This is the first report that shows the relationship between certain genomic aberrations and clinical resistance to cisplatin-based chemotherapy in ovarian cancer patients based on the comparative genomic hybridization analysis. Present findings suggest that these chromosomal gains may be potential indicators for prediction of resistance in ovarian cancer patients before cisplatin-based chemotherapy.

Antineoplastic Agents↗
PubMed1999

[Clinical outcome of an anticancer agent screening test with primary culture cells].

Cancer cells are tested for sensitivity to anticancer agents before the drugs are used for treatment in clinical settings, but the results of these tests have not always been reported fully. Since 1973, one of the authors (Hirono) has been performing sensitivity tests of anticancer drugs by using primary culture cells derived from human cancer tissue, taking into account in vivo status and taking great care to reduce the number of procedural errors. From 1991, flow cytometry has also been adopted for use in anticancer drug sensitivity tests. In the present study, the outcomes of cancer patients were compared by dividing them into a group treated only with anticancer agents to which cancer cells had responded in sensitivity tests, and a group treated with other drugs. The subjects consisted of 132 patients with endometrial cancer stage III (n = 26) and IV (n = 10), ovarian cancer stage III (n = 26) and IV (n = 7), peritonitis carcinomatosa (n = 18), and suspected advanced ovarian cancer (n = 45). There was a significant prolongation in median survival time and survival time among the non-survivors according to the results of a Kaplan-Meier analysis. These findings suggest that sensitivity testing of cancer cells to anticancer drugs should be performed before the start of cancer chemotherapy in the clinical setting.

Adult↗
PubMed1998

Cloning and mapping of ZNF231, a novel brain-specific gene encoding neuronal double zinc finger protein whose expression is enhanced in a neurodegenerative disorder, multiple system atrophy (MSA).

A novel brain-specific gene, neuronal double zinc finger protein (ZNF231), was cloned and mapped. We used the high-density cDNA filter method to analyze the gene-expression profile in brains with multiple system atrophy (MSA). MSA is a sporadic progressive neurodegenerative disease characterized clinically by cerebellar symptoms, parkinsonism, autonomic dysfunction, or their various combinations, but its pathogenesis has yet to be clarified. In total, 8300 cDNA clones were screened, and a novel gene, ZNF231, was identified, whose expression was elevated in cerebella of patients with MSA. Its transcript is approximately 16 kb long and encodes an open reading frame of 3926 amino acid residues that has several interesting motifs; two glycine-proline dipeptide repeats (aa 22-32 and aa 61-74), a pair of homologous C8 double zinc finger motifs (aa 169-226 and aa 465-521), a leucine zipper motif (aa 561-582), a SH3 domain-binding motif (aa 825-831), two nuclear targeting signals (aa 1011-1028 and aa 1071-1091), two glutamine-rich domains (aa 2428-2473 and aa 3775-3804), and a histidine-rich domain (aa 3597-3682). These features suggest that the new gene encodes a nuclear protein or transcription regulator. Northern blot and RT-PCR analyses showed that its expression is specific to the brain and apparently restricted to the neurons. Elevation of ZNF231 expression may be involved in the pathogenesis of multiple system atrophy. The gene for ZNF231 is located on chromosome 3p21.

Amino Acid Sequence↗
PubMed1998

Molecular cloning, differential expression, and chromosomal localization of human frizzled-1, frizzled-2, and frizzled-7.

cDNAs for three human Wnt receptors, Frizzled-1 (FZD1), Frizzled-2 (FZD2), and Frizzled-7 (FZD7), have now been cloned and characterized. The FZD1, FZD2, and FZD7 genes encode the 647-, 565-, and 574-amino-acid proteins, respectively. FZD1, FZD2, and FZD7 share a common structure consisting of seven transmembrane domains, a cysteine-rich domain in the N-terminal extracellular region, and the C-terminal Ser/Thr-Xxx-Val motif. Relatively large amounts of FZD 1 mRNA, 4.5 kb in size, were detected in adult heart, placenta, lung, kidney, pancreas, prostate, and ovary and in fetal lung and kidney. FZD2 mRNAs 4.0 and 2.4 kb in size were detected in adult heart, fetal brain, lung, and kidney. The level of FZD7 mRNAs 5.0 and 4.0 kb in size was high in adult skeletal muscle and fetal kidney, followed by fetal lung, adult heart, brain, and placenta. The FZD1 and FZD7 genes have been mapped to human chromosome 7q21 and 2q33, respectively.

Adult↗
PubMed1998

Identification of the five hydrophilic residues (Lys-217, Lys-218, Arg-359, His-360, and Arg-513) essential for the structure and activity of vitamin K-dependent carboxylase.

Vitamin K-dependent carboxylase catalyzes the posttranslational conversion of glutamic acid to gamma-carboxyglutamic acid in vitamin K-dependent proteins. The clustered charged-to-alanine scanning mutagenesis of bovine carboxylase has identified five distinct candidate regions (I. Sugiura et al., J. Biol. Chem. 271, 17837-17844, 1996) with significant loss-of-function phenotype. To further specify the residues essential for the structure and function of the enzyme, Lys-217, Lys-218, Arg-359, His-360, Lys-361, Arg-513, and Lys-515 were analyzed by substituting to alanine individually. All the mutants except for K217A were expressed in Chinese hamster ovary cells. The carboxylase activities of R359A, H360A, and R513A decreased in parallel with the vitamin K epoxidase activities. Both carboxylations by R359A and H360A were stimulated saturatively at 1 microM factor IX propeptide (proFIX18) concentration, but that by R513A was not at a concentration up to 128 microM. K218A completely lost the enzyme activities but it cross-linked to the propeptide, suggesting that Lys-218 is critical for enzyme activity without affecting propeptide binding. We conclude that Lys-218, Arg-359, and His-360 are involved in the catalytic event, and Arg-513 participates in propeptide binding.

Alanine↗
PubMed1998

Cloning and chromosomal localization of a paralog and a mouse homolog of the human transaldolase gene.

A sequence homologous to the transaldolase gene (TALDO) was identified in a polymorphic cosmid DNA mapped on human chromosome 11p15 by exon trapping with pSPL3. Analysis of lambda clones contiguous to the cosmid clone showed that the related gene (TALDOR) consists of 8 exons spanning approximately 19kb from the translation start site to the polyadenylation signal. The exon sequence of TALDOR was almost identical with that of TALDO localized on 1p33-34. 1, but its exons corresponding to exons 4 and 5 of TALDO were found to be split by 4 introns in TALDOR. To examine the evolutionary conservation of two genes for transaldolase, we have isolated the cDNA for its mouse homolog and determined the nucleotide sequence covering the complete coding region. Fluorescence in situ hybridization using the cDNA as a probe showed that the mouse transaldolase gene (Taldo) is localized on chromosome 7 F3-F4 as a single copy gene. This chromosomal region is known to be syntenic to human chromosome 11p15 rather than to 1p33-p34.1, suggesting that TALDOR is the ancestral form. The existence of TALDOR implies a duplication of the mammalian transaldolase gene after divergence of rodent and primate.

Amino Acid Sequence↗
PubMed1998

Molecular cloning of human Frizzled-6.

The Frizzled genes encode receptors for WNTs, secreted glycoproteins implicated in development as well as in carcinogenesis. In this paper, we report molecular cloning of Hfz6, the human homologue of Mfz6. Nucleotide sequence analysis showed that the Hfz6 gene encodes the 706 amino-acid protein with seven transmembrane domains, a cystein-rich domain in the N-terminal extracellular region, two N-linked glycosylation sites, and two cystein residues in the second and third extracellular loops. Hfz6 mRNA 4.4-kb in size was detected in various normal adult and fetal tissues, and a larger amount of Hfz6 mRNA was detected in both fetal lung and fetal kidney. The Hfz6 gene has been mapped to human chromosome 8q22.3-q23.1. In conclusion, we have cloned Hfz6, which encodes a seven-transmembrane receptor with the cystein-rich domain in the N-terminal extracellular region, but without the Ser/Thr-X-Val motif in the C-terminus.

Amino Acid Sequence↗
PubMed1998

Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5).

A cDNA encoding the human homolog of the tumor necrosis factor receptor-associated factor 5 (TRAF5) protein has been molecularly cloned from a cDNA library of Human Daudi B cell line. The sequence analysis revealed that the cDNA encoded a protein of 557 aa residues with a calculated molecular weight of 64,236. The encoded protein has typical structural characteristics shown in the TRAF family of proteins and binds to the cytoplasmic region of lymphotoxin-beta receptor more efficiently than to that of CD40 and CD30. The TRAF5 gene was mapped to the human chromosome 1q32.3-q41.1. Overexpression of human TRAF5 activates NF kappa B transcription factor in human 293T kidney cells. These results suggest that the human TRAF5 protein could be involved in the signal triggered by various members of the tumor necrosis factor receptor (TNFR) superfamily including CD40, CD30 and lymphotoxin-beta receptor.

Amino Acid Sequence↗
PubMed1998

Relationship between Joint National Committee-VI classification of hypertension and ambulatory blood pressure in patients with hypertension diagnosed by casual blood pressure.

BACKGROUND: White-coat hypertension has been diagnosed arbitrarily based on different criteria. In 1997, the Joint National Committee-VI (JNC-VI) reported a new classification of hypertension and strongly emphasized the importance of ambulatory blood pressure (ABP) monitoring. The report pronounced normal ABP values for the first time. HYPOTHESIS: The study's aim was to clarify the relationship between casual blood pressure (BP) and ABP of patients with essential hypertension in each stage of JNC-VI classification, and the prevalence of white-coat hypertension diagnosed by using JNC-VI normal ABP criteria. METHODS: Ambulatory blood pressure was monitored non-invasively in 232 patients with essential hypertension whose casual BP was > or = 140/90 mmHg. The patients were classified according to JNC-VI classification, and their casual BP was compared with ABP. The criterion of white-coat hypertension was defined as casual BP > or = 140/90 mmHg with normal ABP according to JNC-VI criteria (< 135/85 during daytime and < 120/75 during nighttime). RESULTS: Mean ABP increased as the stage advanced, and the differences between casual BP and ABP also increased. There were considerable overlaps in the distribution of ABP among stages. The prevalence of white-coat hypertension was 13% overall: 30% of the patients with isolated systolic hypertension, 19% of those in stage 1, 10% in stage 2, and 4% in stage 3. CONCLUSIONS: Classification of hypertension based on casual BP may not always correspond in severity to that based on ABP. Ambulatory blood pressure monitoring recommended by JNC-VI is very useful for the evaluation of hypertension to differentiate white-coat hypertension from true hypertension.

Adult↗