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Biomedical subjects

T Mukai

Publications and source records attributed to T Mukai.

At least 109 records · Page 6Linked to original sources
PubMed1998

A novel gene, ITM, located between p57KIP2 and IPL, is imprinted in mice.

We searched for new imprinted genes using a positional cloning method in a region of human chromosome 11p15.5, which contains several imprinted genes including p57KIP2 and IPL, and found a novel ITM gene located between p57KIP2 and IPL. We also obtained the mouse homologue Itm in its syntenic region of mouse chromosome 7. In humans, its location is 17 kb centromeric to p57KIP2 and 3 kb telomeric to IPL, and in mice, 15 kb and 2.5 kb, respectively. They are expressed in most tissue, but especially in the kidney and liver, and moderately in the heart, lung and testis. Mice exhibit a functional imprinting resulting in higher expression of maternal alleles in fetal, newborn and most adult tissues, but it is biallelically expressed in the adult kidney and liver where expression is the highest. In addition to the discrepancy between the level of expression and the strength of the imprint, Itm has several unusual features for an imprinted gene, including large introns, moderate GC content and the absence of direct repeats. Our results will be helpful in understanding the intricate regulatory mechanism of imprinted genes.

Amino Acid Sequence↗
PubMed1998

Characterization of temperature rise of the brain and the rectum following intracerebroventricular administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and kainate in rats.

Intracerebroventricular administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) or kainate caused a rise of the temperature of the brain and the rectum in urethane-anesthetized rats. An AMPA-kainate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), significantly suppressed the AMPA- and kainate-induced rises of brain and rectal temperatures. An N-methyl-d-aspartate receptor antagonist, MK-801, also suppressed the rises of the brain and rectal temperatures induced by AMPA or kainate, but the profiles of the suppressive effects of MK-801 were different between rats treated with AMPA and kainate. An antipyretic agent, indomethacin, completely suppressed the AMPA-induced rises of brain and rectal temperatures. Although indomethacin completely suppressed the kainate-induced rise of the rectal temperature as well, the brain temperature was still raised. These findings suggest that distinct mechanisms may be involved in the temperature rise of the brain and the rectum mediated through AMPA and kainate receptor stimulation.

Analgesics, Non-Narcotic↗
PubMed1998

Transcriptional map of 170-kb region at chromosome 11p15.5: identification and mutational analysis of the BWR1A gene reveals the presence of mutations in tumor samples.

Chromosome region 11p15.5 harbors unidentified genes involved in neoplasms and in the genetic disease Beckwith-Wiedemann syndrome. The genetic analysis of a 170-kb region at 11p15.5 between loci D11S601 and D11S679 resulted in the identification of six transcriptional units. Three genes, hNAP2, CDKN1C, and KVLQT1, are well characterized, whereas three genes are novel. The three additional genes were designated BWR1A, BWR1B, and BWR1C. Full-length cDNAs for these three genes were cloned and nucleotide sequences were determined. While our work was in progress, BWR1C cDNA was described as IPL [Qian, N., Franck, D., O'Keefe, D., Dao, D. , Zhao, L., Yuan, L., Wang, Q., Keating, M., Walsh, C. & Tycko, B. (1997) Hum. Mol. Genet. 6, 2021-2029]. The cloning and mapping of these genes together with the fine mapping of the three known genes indicates that the transcriptional map of this region is likely to be complete. Because this region frequently is altered in neoplasms and in the genetic disease Beckwith-Wiedemann syndrome, we carried out a mutational analysis in tumor cell lines and Beckwith-Wiedemann syndrome samples that resulted in the identification of genetic alterations in the BWR1A gene: an insertion that introduced a stop codon in the breast cancer cell line BT549 and a point mutation in the rhabdomyosarcoma cell line TE125-T. These results indicate that BWR1A may play a role in tumorigenesis.

Beckwith-Wiedemann Syndrome↗
PubMed1998

Effects of cardiomyoplasty on right ventricular filling during volume loading.

BACKGROUND: Although cardiomyoplasty (CMP) is thought to improve ventricular systolic function, its effects on ventricular diastolic function are not clear. Especially the effects on right ventricular diastolic filling have not been fully investigated. Because pericardial influences are more pronounced in the right ventricle than in the left ventricle, CMP with its external constraint may substantially impair right ventricular diastolic filling. METHODS: Fourteen purebred adult beagles were used in this study. Seven underwent left posterior CMP, and 7 underwent a sham operation with a pericardiotomy and served as controls. Four weeks later, the hemodynamic effects of CMP were evaluated by heart catheterization before and after volume loading (central venous infusion of 10 mg/kg of 4.5% albumin solution for 5 minutes). RESULTS: In the CMP group, mean right atrial pressure and right ventricular end-diastolic pressure increased significantly from 3.1 +/- 1.2 mm Hg to 6.1 +/- 2.0 mm Hg (p < 0.001) and from 4.0 +/- 1.8 mm Hg to 9.6 +/- 2.5 mm Hg (p < 0.001), respectively. Volume loading in the control group did not significantly increase either variable. Right ventricular end-diastolic volume and stroke volume did not change significantly (from 53 +/- 9.3 mL to 60 +/- 9.0 mL and from 20 +/- 2.3 mL to 21 +/- 3.2 mL, respectively) in the CMP group. In the control group, however, right ventricular end-diastolic volume and stroke volume increased significantly from 45 +/- 7.7 mL to 63 +/- 14 mL (p < 0.05) and from 18 +/- 4.3 mL to 22 +/- 4.2 mL (p < 0.05), respectively. CONCLUSIONS: These results suggest that CMP may reduce right ventricular compliance and restrict right ventricular diastolic filling in response to rapid volume loading because of its external constraint.

Albumins↗
PubMed1998

Pharmacokinetic models to evaluate radiolabeling reagents for protein radiopharmaceuticals.

Pharmacokinetic models were constructed to further estimate the hepatic radioactivity levels derived from bifunctional chelating agents used for radiolabeling of proteins. Both galactosyl-neoglycoalbumin (NGA) and mannosyl-neoglycoalbumin (NMA) were labeled with (111)In using two benzyl-EDTA derivatives. Time-activity profiles for the liver with gallbladder, intestine, and blood after administration of (111)In-labeled NGAs in mice were simultaneously fitted to a multi-compartment model, and the first-order rate constants representing the disappearance from parenchymal cells were obtained. Similarly, a model composed of the blood and liver compartment was constructed, and the disappearance rate constants from nonparenchymal cells were calculated from the biodistribution studies following administrations of (111)In-labeled NMAs. Fitting curves showed good agreements with the experimental data. Each rate constant clearly distinguished the elimination rate of the respective radiometabolite from the liver cells. Thus, quantitative estimations of radiolabeling reagents were performed only by animal biodistribution studies, and the present pharmacokinetic analyses would be useful for screening of newly designed reagents for protein radiopharmaceuticals.

Albumins↗
PubMed1998

Isolation and characterization of novel endogenous digitalis-like factors in the ovary of the giant toad, Bufo marinus.

We have previously described the structures of four novel unconjugated bufadienolides in the ovary of the toad, Bufo marinus. In this study, we report the separation and characterization of three novel bufadienolide conjugates. These compounds were purified by HPLC, and their structures were determined to be 11alpha, 19-dihydroxytelocinobufagin-3-(12-hydroxydodecanoic acid) ester, 11alpha,19-dihydroxytelocinobufagin-3-(14-hydroxy-7-tetra decenoic acid) ester, and 11alpha, 19-dihydroxytelocinobufagin-3-(14-hydroxytetradecanoic acid) ester on the basis of NMR and MS data. Numerous dicarboxylic acid esters of bufadienolides have previously been described, but the three bufadienolide conjugates described in this report differ from previously described esters in that they contain hydroxylated monocarboxylic acids. The function of these three conjugates is not known but they are, like bufotoxins, potent inhibitors of Na+, K+-ATPase and may play a developmental role in the differentiation of toad oocytes.

Animals↗
PubMed1998

Haemagglutination and glycolipid-binding activities of Lactobacillus reuteri.

The carbohydrate-binding activity of Lactobacillus reuteri was studied by haemagglutination (HA), HA inhibition and thin layer chromatography (TLC) overlay assays. Three of the six Lact. reuteri strains examined showed HA activity. Two strains (JCM1081 and JCM1112T) agglutinated neuraminidase-treated, but not untreated, erythrocytes. Strain JCM2762 agglutinated both treated and untreated erythrocytes. The HA activity of JCM 1081 was inhibited by galactose, lactose, methyl beta-galactoside and asialoglycophorin A. Among 12 glycosphingolipids, TLC overlay assay showed that JCM1081 strongly bound to asialo-GM1. These results indicated that JCM1081 bound to the beta-galactosyl residues of the non-reducing terminal of sugar chains of glycoconjugates. The carbohydrate-binding ability of JCM1081 may be responsible for the adhesion of this strain to the mucosal surface of the intestine.

ABO Blood-Group System↗
PubMed1998

Spontaneous regression of malignant lymphoma of the stomach.

We report a case of complete and spontaneous regression of malignant lymphoma of the stomach. A submucosal tumor with central ulceration was detected on the greater curvature of the stomach in a 63-year-old woman. The tumor was diagnosed histopathologically as a diffuse large B-cell lymphoma (REAL classification). The tumor disappeared 18 days later without chemotherapy. Examination at that stage showed Helicobacter pylori (H. pylori), which was later treated with antibiotics. There was no evidence of recurrence of the malignant lymphoma at the last follow-up conducted at the time of preparation of this report, 13 months after the initial diagnosis. Spontaneous regression of an intermediate and high-grade non-Hodgkin's lymphoma is uncommon. We discuss the possible role of H. pylori in the regression of gastric malignant lymphomas.

Biopsy↗
PubMed1998

Comparative reverse transcription-polymerase chain reaction and in situ hybridization analyses of human imprinted p57KIP2 and insulin-like growth factor 2 gene transcripts in fetal kidney and Wilms' tumors using archival tissue.

p57KIP2 (KIP2) is a cyclin-dependent kinase inhibitor that arrests cells in G1 and an imprinted gene mapped on chromosome 11p15.5. To investigate the role of KIP2 in Wilms' tumor (WT), DNA and RNA were extracted from archival tissue sections of WT. KIP2 expression was investigated by reverse transcription-polymerase chain reaction and in situ mRNA hybridization. Thirteen of 39 WT were informative for length polymorphism of KIP2 and subjected to reverse transcription-polymerase chain reaction. KIP2 was expressed predominantly from one allele, although a low level of expression was also detected from the other. Three WT with loss of heterozygosity at the KIP2 locus demonstrated that the remaining KIP2 allele was still active, which was also confirmed by in situ hybridization. Furthermore, among 13 KIP2-informative WT, 2 were heterozygous for insulin-like growth factor II (IGF2). Allele-specific analysis demonstrated that one showed monoallelic IGF2 expression, whereas the other showed biallelic expression. In situ hybridization of fetal kidney showed that KIP2 transcripts were detected in a variety of cell types, among which differentiated epithelial structures showed higher expression than undifferentiated mesenchyme, whereas IGF2 was expressed predominantly in undifferentiated mesenchyme and renal vesicles of an early phase. WT demonstrated KIP2 and IGF2 hybridization patterns similar to fetal kidney in that KIP2 transcripts were detected in epithelial structures and blastema, whereas IGF2 transcripts were seen in blastema and immature epithelial structures. Hybridization results indicated that KIP2 expression in WT did not appear to be significantly reduced compared with that in fetal kidney and that WT demonstrated a significant amount of KIP2 transcripts regardless of retention or loss of heterozygosity at the KIP2 locus. These data suggest that although KIP2 may play a role in differentiation of the fetal kidney, it is not likely as a tumor suppressor gene, which is implicated as the cause of the development of a majority of WT.

Alleles↗
PubMed1998

Malignant lymphoma of the gingiva: MR evaluation.

PURPOSE: Our purpose was to document the MR imaging findings of malignant lymphoma of the gingiva. METHODS: Five patients with histologically proved malignant lymphoma of the gingiva were studied by MR imaging. The MR images were analyzed for tumor size, extent, and signal characteristics, bone involvement, and associated cervical lymph node enlargement. RESULTS: Clinical examination tended to underestimate the size of lymphomatous lesions. The signal intensity of the lesions was isointense to hyperintense relative to muscle on noncontrast T1-weighted images and showed variable contrast enhancement patterns. On T2-weighted images, signal intensity was isointense to hypointense relative to the oral mucosa. In one case, the mass extended to the submandibular space; in the remaining cases, the masses were limited to the gingiva and the adjacent bone. MR imaging revealed that gingival lymphomatous masses were broad-based along the mandible or maxilla and eroded through the cortex into the marrow space, but the cortex was still recognizable. No nodal involvement was noted in any of the patients with malignant lymphoma. CONCLUSION: The signal characteristics of gingival lymphoma overlap those of other tumors. The cortex separating marrow involvement from the broad-based gingival mass generally appears to be permeated with small erosions but is still recognizable.

Aged↗
PubMed1998

[Evaluation of blood flows inside hepatic tumors using color Doppler echography with galactose-based intravenous contrast medium "SH/TA 508" administration].

The purpose of this study is to evaluate hemodynamic characteristics of various hepatic tumors using color Doppler echography administered galactose-based intravenous contrast medium "SH/TA 508 (Levovist)". Subject were 9 cases of hepatocellular carcinomas, 5 cases of metastatic liver tumors and a case of hemangioma. We evaluated the characteristics of blood flows inside various hepatic tumors, and also evaluated the first pass through the hepatic tumors during administration of Levovist. The strongly pulsatile branched blood flows inside tumor and the slow-increased and plateau patterns were observed in the all cases of hepatocellular carcinomas, the weakly pulsatile blood flows surrounding tumor and the rapid-increased and slow-decreased patterns were observed in the cases of metastatic liver tumors, and the continuous blood streams in the margin of tumor and the slow-increased and slow-decreased pattern were observed in the case of hemangioma. These findings were characteristic in various hepatic tumors, and color Doppler echography enhanced by Levovist was very useful to distinguish hepatic tumors.

Carcinoma, Hepatocellular↗
PubMed1997

Bone mass loss due to estrogen deficiency is compensated in transgenic mice overexpressing human osteoblast stimulating factor-1.

Osteoblast stimulating factor-1 (OSF-1) stimulates in vitro proliferation and differentiation of osteoblastic cells, and its gene is expressed in the bone and brain tissues in mammals and amphibians. To evaluate the in vivo function of OSF-1 in bone metabolism, transgenic mice overexpressing the human osf-1 gene driven by the osteocalcin promoter were generated. Femoral bone mineral content was increased in transgenic mice relative to wild-type controls as estimated by ash assay, depending on the transgene copy number per cell. In ovariectomized mice, bone mass loss due to estrogen deficiency was observed in both transgenic and control mice but bone mass was still higher in transgenic mice than in controls. Bone mass in ovariectomized transgenic mice was comparable to that in wild-type mice without ovariectomy. These observations indicate that OSF-1 may direct in vivo appositional bone formation by increasing osteoblast activity rather than decreasing osteoclast activity, suggesting a new way to treat osteoporosis with OSF-1.

Animals↗
PubMed1997

Inhibition of NMDA-induced increase in brain temperature by N-omega-nitro-L-arginine and indomethacin in rats.

Intracerebroventricular administration of N-methyl-D-aspartate (NMDA) caused an increase in brain temperature, which appeared rapidly and preceded that in rectal temperature, in urethane-anesthetized rats. The increase in brain temperature was divided into two phases, an early increase and a late increase. Intracerebroventricular indomethacin, a cyclooxygenase inhibitor, completely abolished the NMDA-induced late increase, but not the early increase, in brain temperature. On the other hand, intracerebroventricular N-omega-nitro-L-arginine, a potent inhibitor of nitric oxide synthase, strongly suppressed both the early and the late increases. These findings suggest that both nitric oxide and prostaglandins may be involved in the increase in brain temperature after NMDA receptor activation.

Animals↗
PubMed1997

Aberrant methylation of an imprinted gene U2af1-rs1(SP2) caused by its own transgene.

Genomic imprinting refers to the parental allele-specific expression of genes. The precise mechanism underlying this phenomenon, which may involve DNA methylation, is not yet known. U2af1-rs1(SP2) is an imprinted gene expressed from the paternal allele and is methylated on the maternal allele. Here we report an artificial system in which expression and methylation of the endogenous imprinted gene U2af1-rs1 can be affected by interaction with its own transgene in the testis. We suggest that there is a mechanism in male gametogenesis by which the U2af1-rs1 gene is kept unmethylated to be expressed in the offspring in addition to a mechanism in female gametogenesis by which the U2af1-rs1 gene is methylated and is not expressed in the offspring.

Alleles↗
PubMed1997

Cloning and expression of cDNA encoding heart-type isoform of AMP deaminase.

Mouse cDNA for the heart-type (H) isoform of AMP deaminase (EC 3.5.4.6., AMPD) has been isolated and characterized. The cDNA for the Ampd gene expressed in heart is predicted to encode a peptide of 766 amino acids with a molecular mass of 88 kDa. The coding region of this cDNA was quite homologous to the human AMPD3 gene which encodes the erythrocyte-type (E) isoform of AMPD, although the H-isoform of rodent AMPD was reported to be immunologically distinct from the E-isoform of human AMPD. The non-coding region of the isolated cDNA is not homologous to human AMPD3, while rodent Ampd1 has similarity to human AMPD1 in the non-coding region as well as in the coding region. The transcripts for the cloned cDNA were expressed in heart, slow-twitch skeletal muscle and non-muscle tissues. Prokaryotic expression showed that this cDNA encodes a catalytically active enzyme which reacts to the specific antibody raised to the H-isoform of AMPD.

AMP Deaminase↗
PubMed1997

Hair analysis for drug abuse. XIV. Identification of substances causing acute poisoning using hair root. I. Methamphetamine.

A hair root was evaluated as a specimen for proving acute methamphetamine (MA) poisonings using an animal model and fatal cases of MA intoxicaton. First of all, male pigmented hairy rats (n = 5) were administered with acute poisonous doses (20, 40 and 60 mg/kg) of MA and the hair roots were plucked out with a hair nipper 5 min and 0.5, 1, 2, 6 and 24 h after i.p. injection. The hair root samples were, directly or after washing with detergent, extracted with methanol/5 N HCl (20:1) under vortex mixing at room temperature for 14 h. After evaporation, the residue was derivatized with pentafluoropropionic anhydride and analyzed with GC/MS. From all samples including a 5-min sample, MA was detected at high concentrations (approximately 150 ng/mg) with a small amount of amphetamine (AP). Many animals died within 120 min of administration, but the concentrations in the hair roots increased up to 120 min and then slowly decreased until 24 h. Although MA was definitely detected anytime in the hair roots, almost no MA was found in 24-h plasma. In comparison of the drug levels in hair roots between the washed group and the unwashed group, the levels of the washed group were as a whole 4-5-fold higher than those of the unwashed group. These differences show that most of the drug incorporated into hair root is still not immobilized in the early stage. The ratios of the MA remainder in the washed samples increased with the elapse of time in all cases. However, the slope of the curves definitely dropped after the death of rats, probably due to the stopping of the hair growth and the incorporation of drug into the hair shaft. The ratios of AP/MA after death became a plateau probably due to the stoppage of the activity of metabolism after death, while those before death had increased over time. We analyzed the specimens of hair root of four men who died mainly due to acute poisonings with MA. Consequently, MA in the hair roots was detected at high concentrations, 30.5-134.6 ng/mg, and its metabolic, AP, at the concentrations of 1.2-9.0 ng/mg. Our results suggested that hair root is a good specimen for probing acute MA poisoning.

Acute Disease↗
PubMed1997

Premenstrual mood changes and maternal mental health in pregnancy and the postpartum period.

To investigate the relationship between premenstrual mood changes and maternal mental health in the perinatal period, a prospective questionnaire survey of 1,329 women was carried out. Women with a premenstrual mood changes (irritability) before pregnancy showed significantly higher Zung's Self-rating Depression Scale (SDS) scores than those without it, throughout pregnancy and the postpartum period (6 time points: early, middle, and late pregnancy, 5 days, 1 month, and 6 months after childbirth). In addition, women with premenstrual irritability had greater anxiety about pregnancy and delivery, were more reluctant to accept mother roles, and felt their babies (fetuses or neonates) were more vulnerable. These findings suggest that premenstrual mood change is correlated with unstable mental health throughout the perinatal period.

Adolescent↗