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Biomedical subjects

K Imai

Publications and source records attributed to K Imai.

At least 325 records · Page 18Linked to original sources
PubMed1999

Developmental toxicity of the topoisomerase inhibitor, etoposide, in rabbits after intravenous administration.

The developmental effect of the topoisomerase inhibitor, etoposide, was investigated in pregnant rabbits given intravenous doses during early organogenesis. Does received 0, 0.25, 0.5, 1, or 2 mg/kg/day on days 7 through 9 of gestation. Fetal parameters were evaluated on day 28 of gestation. Live fetuses were examined for gross, visceral, and skeletal malformations and variations. In addition, telencephalon in embryos 8 h following the final treatment was examined histologically. No change in general condition was observed in any does, but a significant decrease in body weight gain during the pregnancy and enlargement of the liver resulting from marked fatty change were observed in does treated with etoposide at 2 mg/kg/day. Etoposide had neither lethal nor growth retarded effects on embryos/fetuses. However, axial skeletal malformation and extra ribs had a low incidence but were significant in the group treated with etoposide at 2 mg/kg/day, whereas no significant increases in external malformations in term fetuses nor in pyknotic cells in the ventricular zone of telencephalon in embryos were noticed in any etoposide-treated groups. It was concluded that anatomical defects (skeletal malformation or variation) in rabbits were induced by intravenous etoposide treatment during early organogenesis and that they occurred in the presence of maternal toxicity.

Abnormalities, Drug-Induced↗
PubMed1999

The pleckstrin homology domain of the Wiskott-Aldrich syndrome protein is involved in the organization of actin cytoskeleton.

In this study, we investigated the role of the pleckstrin homology (PH) domain of the Wiskott-Aldrich syndrome protein (WASP) in the regulation of actin cytoskeleton, which is defective in patients with Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT). Overexpression of the WASP in COS-7 cells cultured in the presence of fetal calf serum (FCS) resulted in large cluster formation of polymerized actin and WASP in the cytoplasm. In contrast, when the WASP transfected cells were cultured in the absence of FCS, activation with PMA or EGF was required to induce cluster formation. Overexpression of WASP with a missense mutation in the N-terminus of the PH domain failed to induce the large cluster formation in COS-7 cells even in the presence of FCS. We also found that phosphatidylinositol 4,5-bisphosphate (PIP(2)), which is known to regulate the actin cytoskeleton, binds to the PH domain of WASP, and the binding was abolished by the introduction of a missense mutation into the N-terminus but not the C-terminus of the PH domain. Together with the observations that most of the missense mutations observed in patients with WAS and XLT are located within the PH domain, these results indicate that the PH domain of WASP plays important roles in the regulation of actin cytoskeleton and suggested that the binding of PIP(2) to the PH domain is necessary for WASP to function properly.

Actins↗
PubMed1999

Alteration in the D-amino acid content of the rat pineal gland under anesthesia.

In a previous report (Hamase, K. et al., Biochim Biophys Acta 1134: 214-222 (1997)), we showed that the rat pineal gland contains D-leucine (D-Leu) as well as D-aspartic acid (D-Asp). In this communication we report alterations in the content of these D-amino acids during anesthesia. The D-Asp content was significantly increased from 2.8 to 5.0, 4.8 and 5.8 nmol/pineal gland by administration of ether, urethane and pentobarbital, respectively. In contrast, the D-Leu content was decreased by administration of urethane or pentobarbital. The D-Leu content decreased from 4.2 to 2.2 pmol/pineal gland 4 hours after administration of urethane, although the content remained unchanged until 1.5 hours after administration. The content of the L-enantiomers of these amino acids were not affected by anesthesia. The urethane-induced decrease in D-leucine content was almost completely suppressed by a beta-agonist, (-)-isoproterenol, whereas the agonist itself had no effect.

Adrenergic beta-Antagonists↗
PubMed1999

Isolation and characterization of the fission yeast gene rpa42+, which encodes a subunit shared by RNA polymerases I and III.

Eukaryotic RNA polymerases I and III share two distinct alpha-related subunits that show limited homology to the alpha subunit of Escherichia coli RNA polymerase, which forms a homodimer to nucleate the assembly of prokaryotic RNA polymerase. To gain insight into the functions of alpha-related subunits in eukaryotes, we have previously identified the alpha-related small subunit RPA17 of RNA polymerase I (and III) in Schizosaccharomyces pombe, and have shown that it is a functional homolog of Saccharomyces cerevisiae AC19. In an extension of that study, we have now isolated and characterized rpa42+, which encodes the alpha-related large subunit RPA42 of S. pombe RNA polymerase I, by virtue of the fact that its product interacts with RPA17 in the yeast two-hybrid system. We have found that rpa42+ encodes a polypeptide with an apparent molecular mass of 42 kDa, which shows 58% identity to the AC40 subunit shared by RNA polymerases I and III in S. cerevisiae. Furthermore, we have shown that rpa42+ complements a temperature-sensitive mutation in RPC40 the gene that encodes AC40 in S. cerevisiae and which is essential for cell growth. Finally, we have shown that neither RPA42 nor RPA17 can self-associate. These results provide evidence that the two distinct alpha-related subunits, RPA42 and RPA17, of RNA polymerases I and III are functionally conserved between S. pombe and S. cerevisiae, and suggest that heterodimer formation between them is essential for the assembly of RNA polymerases I and III in eukaryotes.

Amino Acid Sequence↗
PubMed1999

Blood flow of the gluteus medius muscle. An animal study.

We investigated the effects of subperiosteal dissection on blood flow in the gluteal medius muscle in adult rabbits using the hydrogen washout technique. After the control blood-flow rate was determined, 8 rabbits were separated into 2 groups according to the direction of the dissection. The gluteal medius muscle was dissected from the iliac crest in the proximal-distal direction in 10 hips. In another 6 hips, the greater trochanter was osteomised and the gluteus medius muscle was dissected from the ilium in the distal-proximal direction. Dissection of the middle third of the gluteus medius muscle caused the most significant reduction in blood flow, more than 50% in both groups. This result indicates that minimising damage to the mid-portion of the gluteus medius muscle is important for reducing the incidence of post-operative complications.

Angiography↗
PubMed1999

Nucleotide sequences of the mouse globin beta gene cDNAs in a wild derived new haplotype Hbb(w1).

Haplotypes of the beta-globin gene complex (Hbb) in laboratory mice have been defined as d, p, and s. We previously found a new haplotype w1 in wild mice collected from northwestern China. This study analyzed the nucleotide sequences of b1 and b2-globin gene cDNAs of both the p and w1 haplotypes, in comparison with those of the d haplotype. In Hbb-b1 cDNA, six base substitutions were found between the d and w1 haplotypes and also between p and w1, but none existed between d and p. In Hbb-b2 cDNA, three base substitutions were found between the d and w1 haplotypes and also between d and p, but none between p and w1. This result indicated that the Hbb gene complex of the p haplotype carries b1(d) and b2(w1) genes and is probably a recombinant between d and w1 haplotypes. The hemoglobin containing the W1 phenotype showed oxygen-binding properties identical with those of the hemoglobins containing D and P phenotypes.

Animals↗
PubMed1999

The fission yeast rpa17+ gene encodes a functional homolog of AC19, a subunit of RNA polymerases I and III of Saccharomyces cerevisiae.

Eukaryotic RNA polymerases I and III consist of multiple subunits. Each of these enzymes includes two distinct and evolutionarily conserved subunits called alpha-related subunits which are shared only by polymerases I and III. The alpha-related subunits show limited homology with the alpha-subunit of prokaryotic RNA polymerase. To gain further insight into the structure and function of alpha-related subunits, we cloned and characterized a gene from Schizosaccharomyces pombe that encodes a protein of 17 kDa which can functionally replace AC19 - an alpha-related subunit of RNA polymerases I and III of Saccharomyces cerevisiae - and was thus named rpa17+. RPA17 has 125 amino acids and shows 63% identity to AC19 over a 108-residue stretch, whereas the N-terminal regions of the two proteins are highly divergent. Disruption of rpa17+ shows that the gene is essential for cell growth. Sequence comparison with other alpha-related subunits from different species showed that RPA17 contains an 81-amino acid block that is evolutionarily conserved. Deletion analysis of the N- and C-terminal regions of RPA17 and AC19 confirms that the 81-amino acid block is important for the function of the alpha-related subunits.

Amino Acid Sequence↗
PubMed1999

Association of cyclin D1 expression with factors correlated with tumor progression in human hepatocellular carcinoma.

The amplification and/or rearrangement of the cyclin D1 gene, a positive regulatory element of the G1 to S phase of the cell cycle, has been reported in various human tumors, suggesting an oncogenic role of this gene. In this study, we investigated the expression of cyclin D1 in the formalin-fixed and paraffin-embedded human hepatocellular carcinoma (HCC) tissues of 25 patients, using monoclonal antibody 5D4 raised against cyclin D1. Two distinct patterns of staining were observed in HCC cells, nuclear and cytoplasmic. The nuclear staining pattern of cyclin D1 was detected in the tissues of only 2 of the 25 HCC patients (8%) examined and no particular clinicopathological characteristics were found in these patients. In contrast, the cytoplasmic staining pattern, without nuclear staining, was detected in 8 of the 25 patients with HCC (32%). A significant correlation was found between the expression of cytoplasmic cyclin D1 and patients with tumor thrombus in the portal vein (Vp), as well as those with intrahepatic metastasis (IM). These results indicate that the cytoplasmic cyclin D1 expression appears to be related to the prognosis of HCC. The Ag nucleolar organizer regions (NORs) counts in cyclin D1-positive and -negative patients were not significantly different, suggesting that immunostaining for cyclin D1 has the potential to be a unique prognostic marker in human HCC. Simultaneous immunohistochemical study with p53 antibody in the same series of HCC revealed that 88% of the patients positive for cyclin D1 also expressed p53 and that in 91% of the patients negative for p53, cyclin D1 was not expressed. These results suggest that cyclin D1 is expressed later than the alteration of p53 in the progression of human HCC.

Adult↗
PubMed1999

First detection of bovine group B rotavirus in Japan and sequence of its VP7 gene.

An epizootic outbreak of diarrhea occurred in adult cows on a dairy farm in Hokkaido, Japan. One colostrum-fed calf inoculated with pooled feces of the 5 affected cows, developed mild diarrhea, and shed rotavirus-like particles which reacted with antiserum to group B rotavirus in immune electron microscopy. Cell culture immunofluorescence tests, RNA-polyacrylamide gel electrophoresis and RT-PCR confirmed that this virus was bovine group B rotavirus, which was designated the Nemuro strain. Additional 2 colostrum-deprived calves inoculated with feces of the first calf also developed diarrhea and shed virus, suggesting that this group B rotavirus might be the etiological agent of the outbreak of adult cow diarrhea. The identities of the nucleotide (nt) and deduced amino acid (aa) sequences of the Nemuro VP7 gene were high (93-95% in nt and 96-97% in aa) and low (61-63% in nt and 49-61% in aa) compared to those of the published corresponding genes from 3 bovine and 2 other mammalian (human and rat) strains of group B rotaviruses, respectively. To our knowledge, this is the first report on the presence of bovine group B rotavirus in Japan.

Amino Acid Sequence↗
PubMed1999

Gastric cancers of the microsatellite mutator phenotype display characteristic genetic and clinical features.

BACKGROUND & AIMS: Colon cancer of the microsatellite mutator phenotype (MMP) exhibits significant genotype differences from cancer without the MMP. Twenty-nine MMP-positive gastric cancers were analyzed to clarify if these genotype differences were also associated with distinctive clinicopathologic features. METHODS: Alterations of p53, beta2-microglobulin (beta2M ), hMLH1, and hMSH2 genes were analyzed by using polymerase chain reaction, single-strand conformational polymorphism, sequencing, microallelotyping, hypermethylation assays, and immunostaining. The results were contrasted with mutations in BAX, hMSH3, and hMSH6, genes target for the MMP. RESULTS: Tumors with the MMP had a significantly lower incidence of p53 gene mutations than the other tumors and often contained beta2M gene somatic mutations. Many tumors contained concomitant genetic and epigenetic alterations in DNA mismatch repair genes, hMLH1, hMSH2, hMSH3, and hMSH6. Gastric cancer of the MMP was associated with well/moderate differentiation, distal location, and better survival. CONCLUSIONS: Analysis of somatic alterations in microsatellite sequences and in cancer genes target for the MMP is useful for the classification of groups of gastric cancers with different prognosis. The results further support the concept that (gastric) cancer of the MMP represents a distinctive oncogenic pathway because the mutated cancer genes are usually different from those found in tumors without the MMP.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Preparation of specific antisera to 15alpha-hydroxyestrogens.

The synthesis of haptens of 15alpha-hydroxyestrone, 15alpha-hydroxyestradiol, and 15alpha-hydroxyestriol (estetrol) was undertaken, to obtain specific antisera required for enzyme immunoassay. 3-(1-Carboxypropyl) ethers of these 15alpha-hydroxyestrogens were prepared and conjugated with bovine serum albumin and horseradish peroxidase. The specificity of antisera elicited against bovine serum albumin conjugates was checked by the enzyme immunoassay by using horseradish peroxidase-labeled antigen, and proved to be satisfactory in terms of cross-reactivities to related compounds.

Animals↗
PubMed1999

A comparative study of high-dose and low-dose ACTH therapy for West syndrome.

PURPOSE: A prospective randomized controlled study was conducted for the purpose of identifying the lowest effective ACTH dose, with the fewest adverse effects, for the treatment of West syndrome (WS). SUBJECTS AND METHODS: Twenty-five subjects with cryptogenic (CWS, n = 9) or symptomatic (SWS, n = 16) WS were enrolled in this study. They were randomly assigned to receive either low-dose (0.005 mg/kg per day = 0.2 IU/kg per day) or high-dose (0.025 mg/kg per day = 1 IU/kg per day) synthetic ACTH therapy. ACTH was administered every morning for 2 weeks and tapered to zero over the subsequent 2 weeks. Both effectiveness and adverse effects were compared between the two treatment regimens in each type of WS. RESULT: After completion of the treatment protocol in the CWS group, spasms and hypsarrhythmia were completely suppressed in 3/4 (75%) given the low-dose and 5/5 (100%) given the high-dose treatment. In the SWS group, the spasms and hypsarrhythmia disappeared in 6/8 (75%) in each dose group. There were no significant differences in initial responses between the low-dose and high-dose treatments for either type of WS (P > 0.05). Long-term seizure and developmental outcomes, assessed in the 17 responders who were followed up for longer than 1 year after the completion of ACTH therapy, were also essentially the same. We did not recognize differences in side effect profiles between the two treatment regimens with the exceptions of sleepiness and brain shrinkage estimated by CT scan, both of which were significantly milder in the low-dose than in the high-dose group (P < 0.05). CONCLUSION: Unexpectedly, this prospective randomized controlled study demonstrated the dose of ACTH required for spasm cessation and disappearance of the hypsarrhythmic EEG pattern to be lower than previously believed. A low-dose regimen should thus be considered for CWS, and for SWS associated with significant cerebral atrophy.

Adrenocorticotropic Hormone↗
PubMed1999

Ring chromosome 14 complicated with complex partial seizures and hypoplastic corpus callosum.

A Japanese male with mosaicism of ring chromosome 14 and chromosome 14 monosomy is described. He demonstrated the characteristic morphologic features of ring chromosome 14, in addition to mental retardation and epileptic seizures. Clusters of complex partial seizures, one of which originated in the left frontocentral region on electroencephalographic monitoring, were evident. His seizures responded to phenobarbital, and his mental and motor development was only mildly retarded. Magnetic resonance imaging revealed a hypoplastic corpus callosum, previously unknown in association with this syndrome.

Agenesis of Corpus Callosum↗
PubMed1999

Angiotensin I converting enzyme gene polymorphism and insulin resistance in patients with angina pectoris.

The association between insertion/deletion polymorphism of the angiotensin I converting enzyme (ACE) gene and insulin resistance (IR) was investigated in 64 consecutive patients (F/M: 11/53) with angina pectoris without clinically manifest diabetes mellitus who underwent diagnostic coronary angiography. The observed frequency distribution of ACE genotypes did not deviate from that predicted from the Hardy-Weinberg equilibrium in this group. Patients with the ACE-ID genotype had significantly lower IR, as assessed by an oral glucose tolerance test (OGTT) and by homeostatic model assessment (HOMA), compared to those with the ACE-II genotype, as assessed by a multiple comparison analysis. Patients were divided into two groups with low and high HOMA-IR, and the I allele was seen more frequently in the high HOMA-IR group than in the low HOMA-IR group (0.62 v 0.47, respectively, by chi2 test, P < .05). Logistic regression analysis showed that the odds ratio for insulin resistance in patients with the II genotype, compared to those with the ID and DD-genotypes (assuming that the I allele has a recessive effect), was 4.0 (95% confidence interval, 1.2 to 16.5; P = .037), after adjusting for the presence of significant coronary atherosclerosis. In conclusion, the D allele was not associated with higher insulin resistance in patients with angina pectoris; that is, patients with the ID and DD genotypes were associated with a significantly lower risk of insulin resistance, compared to those with the II genotype.

Aged↗
PubMed1999

Zic1 regulates the patterning of vertebral arches in cooperation with Gli3.

Skeletal abnormalities are described that appeared in Zic1-deficient mice. These mice show multiple abnormalities in the axial skeleton. The deformities are severe in the dorsal parts of the vertebrae, vertebral arches, but less so in the vertebral bodies (spina bifida occulta). The proximal ribs are deformed having ectopic processes. The abnormalities found in the vertebral arches can be traced back to disturbed segmental patterns of dorsal sclerotome. The Zic1/Gli3 double mutants showed severe abnormalities of vertebral arches not found in single mutants. The abnormalities in the vertebral arches were less severe in Zic1/Pax1 mutants than Zic1/Gli3 mutants, but significantly more pronounced than in Zic1 single mutants. The three genes may act synergistically in the development of the vertebral arches.

Animals↗
PubMed1999

Butyrate augments interferon-alpha-induced S phase accumulation and persistent tyrosine phosphorylation of cdc2 in K562 cells.

Interferon-alpha (IFN-alpha) is a clinically useful cytokine for treatment of a variety of cancers, including chronic myelocytic leukaemia (CML). Most CML cells are sensitive to IFN-alpha; however, its biological effects on leukaemic cells are incompletely characterized. Here, we provide evidence that IFN-alpha induces a significant increase in the S phase population in human CML leukaemic cell line, K562, and that the S phase accumulation was augmented by sodium butyrate. In contrast, neither sodium butyrate alone, nor sodium butyrate plus IFN-gamma, affected the cell cycle in K562 cells. These data suggest that the effect of sodium butyrate depended upon IFN-alpha-mediated signalling. The ability of leukaemic cells to exhibit the S phase accumulation after stimulation by IFN-alpha plus sodium butyrate correlated well with persistent tyrosine phosphorylation of cdc2, whereas treatment with IFN-gamma plus sodium butyrate did not affect its phosphorylation levels. Considering that dephosphorylation of cdc2 leads to entry to the M phase, the persistent tyrosine phosphorylation of cdc2 may be associated with the S phase accumulation induced by IFN-alpha and sodium butyrate. In addition, another human CML leukaemic cell line, MEG-01, also showed the S phase accumulation after stimulation with IFN-alpha plus sodium butyrate. Taken together, our studies reveal a novel effect of sodium butyrate on the S phase accumulation and suggest its clinical application for a combination therapy with IFN-alpha, leading to a great improvement of clinical effects of IFN-alpha against CML cells.

Antineoplastic Agents↗