[A clinical case of 13 years old boy of aspirin-induced asthma with food allergy].
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
K Harada
Publications and source records attributed to K Harada.
[Diagnosis of brain tumor with proton MR spectroscopy--the quantification of gliomas compared with normal brain].
We conducted quantification of proton MR spectroscopy (MRS) using water signal as an internal standard, in order to quantify the concentrations of metabolites in normal adult brains and in gliomas in vivo. Single-voxel spectra were acquired using a point-resolved spectroscopic (PRESS) pulse sequence as part of the Probe. P spectroscopy package on a GE Signa Horizon Hispeed LX1.5T scanner (TR/TE/Ave = 3000 msec/30 msec/64). The volume of interest (VOI) varied from 15.0 x 15.0 x 15.0 mm3 to 20.0 x 20.0 x 20.0 mm3 for the brain. The present study included 26 healthy volunteers and 12 patients with gliomas, whose diagnoses were verified by histologic examination. The calculated concentrations of N-acetyl-aspartate (NAA), creatine (Cre) and choline (Cho) in normal hemispheric white matter were 23.66 +/- 1.94 mM (mean +/- SD), 12.97 +/- 1.44 mM, and 4.38 +/- 0.60 mM, respectively. We found they were not necessarily uniform in different parts of the brain, for example, in the pons and basal ganglia. The concentrations of NAA and Cre decreased in all gliomas (p < 0.001). Cho concentration also decreased in the glioma (p < 0.005). The NAA/Cre, NAA/Cho, and Cre/Cho ratios can distinguish normal brain from gliomas, and NAA/Cho ratio can distinguish low-grade astrocytoma from the high-grade group. The results indicate that this noninvasive method offers reasonable estimation of metabolite concentrations in the brain in vivo and therefore is useful in diagnoses of gliomas.
Adult↗
Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes.
To elucidate the physiological role of sterol regulatory element-binding protein-1 (SREBP-1), the hepatic mRNA levels of genes encoding various lipogenic enzymes were estimated in SREBP-1 gene knockout mice after a fasting-refeeding treatment, which is an established dietary manipulation for the induction of lipogenic enzymes. In the fasted state, the mRNA levels of all lipogenic enzymes were consistently low in both wild-type and SREBP-1(-/-) mice. However, the absence of SREBP-1 severely impaired the marked induction of hepatic mRNAs of fatty acid synthetic genes, such as acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase, that was observed upon refeeding in the wild-type mice. Furthermore, the refeeding responses of other lipogenic enzymes, glycerol-3-phosphate acyltransferase, ATP citrate lyase, malic enzyme, glucose-6-phosphate dehydrogenase, and S14 mRNAs, were completely abolished in SREBP-1(-/-) mice. In contrast, mRNA levels for cholesterol biosynthetic genes were elevated in the refed SREBP-1(-/-) livers accompanied by an increase in nuclear SREBP-2 protein. When fed a high carbohydrate diet for 14 days, the mRNA levels for these lipogenic enzymes were also strikingly lower in SREBP-1(-/-) mice than those in wild-type mice. These data demonstrate that SREBP-1 plays a crucial role in the induction of lipogenesis but not cholesterol biosynthesis in liver when excess energy by carbohydrates is consumed.
Acetyl-CoA Carboxylase↗
A crucial role of sterol regulatory element-binding protein-1 in the regulation of lipogenic gene expression by polyunsaturated fatty acids.
Dietary polyunsaturated fatty acids (PUFA) are negative regulators of hepatic lipogenesis that exert their effects primarily at the level of transcription. Sterol regulatory element-binding proteins (SREBPs) are transcription factors responsible for the regulation of cholesterol, fatty acid, and triglyceride synthesis. In particular, SREBP-1 is known to play a crucial role in the regulation of lipogenic gene expression in the liver. To explore the possible involvement of SREBP-1 in the suppression of hepatic lipogenesis by PUFA, we challenged wild-type mice and transgenic mice overexpressing a mature form of SREBP-1 in the liver with dietary PUFA. In the liver of wild-type mice, dietary PUFA drastically decreased the mature, cleaved form of SREBP-1 protein in the nucleus, whereas the precursor, uncleaved form in the membranes was not suppressed. The decreases in mature SREBP-1 paralleled those in mRNAs for lipogenic enzymes such as fatty acid synthase and acetyl-CoA carboxylase. In the transgenic mice, dietary PUFA did not reduce the amount of transgenic SREBP-1 protein, excluding the possibility that PUFA accelerated the degradation of mature SREBP-1. The resulting sustained expression of mature SREBP-1 almost completely canceled the suppression of lipogenic gene expression by PUFA in the SREBP-1 transgenic mice. These results demonstrate that the suppressive effect of PUFA on lipogenic enzyme genes in the liver is caused by a decrease in the mature form of SREBP-1 protein, which is presumably due to the reduced cleavage of SREBP-1 precursor protein.
Animal Feed↗
Tissue Doppler imaging in the normal fetus.
Tissue Doppler imaging is a new non-invasive method that derives measurements of relaxation velocities directly from the myocardium. This approach to studying myocardial velocities offers the potential for quantitative assessment of diastolic ventricular function. Data on myocardial tissue velocities in normal fetuses have not been established. We measured motion velocities of the left ventricular posterior wall, right ventricular anterior wall, interventricular septum along the long axis in 30 normal fetuses aged 19-38 weeks gestation (mean, 26.3+/-6.0 weeks). In all fetuses, peak myocardial velocities during early diastole (EW) and atrial contraction (AW) waves were recorded. The mean values for EW, AW, and E/AW of left ventricle were 5.4+/-1.7, 7.0+/-1.4 cm/s, and 0.77+/-0.19, respectively, and those of right ventricle were 5.5+/-1.5, 7.8+/-1.5 cm/s, and 0.70+/-0.14, respectively. The EW(4.1+/-1.0 cm/s) and the AW (5.3+/-0.8 cm/s) of the interventricular septum were significantly lower than those of the left and right ventricular walls (P<0.01). The EW and E/AW of the left ventricular wall increased significantly with increasing gestational age (r=0.81 and 0.85, respectively, P<0.01). Similar changes were observed in the myocardial velocities of the right ventricular wall. The EW and E/AW of the interventricular septum also increased significantly with age (r=0.63 and 0.78, respectively, P<0.01). However, AW of the interventricular septum showed little changes. In both ventricles, there were significant correlations between tissue Doppler E/AW and pulsed Doppler E/A (LV, r=0.56; and RV, r=0.60, P<0.01). Assessment of myocardial tissue velocities in fetuses is feasible with tissue Doppler imaging. Age-related alterations in tissue Doppler velocities may suggest age-related maturational changes in diastolic function.
Blood Flow Velocity↗
Angiotensin II type 1A receptor knockout mice display less left ventricular remodeling and improved survival after myocardial infarction.
BACKGROUND: Angiotensin II (Ang II) has been implicated in ventricular remodeling after myocardial infarction (MI), which is an important determinant for prognosis after MI. The aim of this study was to determine whether Ang II type 1A receptor (AT(1A))-mediated Ang II signals are critically involved in the mortality and LV remodeling after MI. METHODS AND RESULTS: We examined survival, cardiac geometry and function, cardiac fibrosis, and gene expression of AT(1A) knockout (KO) mice and wild-type (WT) mice at 1 and 4 weeks after large MI. The survival rate was higher in KO mice than in WT mice at 4 weeks after MI. All WT survivors showed severe heart failure, detected by marked increases in both RV weight and lung weight. LV remodeling, such as the development of LV dilatation, LV dysfunction, and cardiac fibrosis at the noninfarcted area, were comparable in both kinds of mice at 1 week after MI. At 4 weeks after MI, however, WT mice showed more marked remodeling than KO mice. mRNA levels of AT(1) at the noninfarcted area were increased from 1 to 4 weeks after MI only in WT mice, whereas levels of AT(2) were not changed by MI in either kind of mouse. Accompanied by the development of geometric and structural remodeling, expression of fetal-type genes, collagen, and transforming growth factor-beta(1) genes were upregulated and sustained in the noninfarcted area of WT hearts. In contrast, they were rapidly downregulated to basal levels at 4 weeks after MI in that of KO hearts. CONCLUSIONS: These results indicate that AT(1A) signals play a pivotal role in the progression of LV remodeling after MI, resulting in overt heart failure.
Animals↗
MAPK superfamily plays an important role in daunomycin-induced apoptosis of cardiac myocytes.
BACKGROUND: Although anthracyclines, such as daunomycin (DM) and adriamycin, are potent chemotherapeutic agents, they have serious adverse effects, including cardiac toxicity. In the present study, we investigated the molecular mechanisms of DM-induced cardiomyocyte impairment. METHODS AND RESULTS: When cultured cardiac myocytes of neonatal rats were exposed to 1 micromol/L DM for 24 hours, many cells became positive for TUNEL staining, with morphological changes characteristic of apoptosis. Fragmentation of DNA into oligonucleosome-size fragments was recognized by agarose gel electrophoresis in DM-treated myocytes. DM activated 3 members of the mitogen-activated protein kinase (MAPK) family dose-dependently, such as extracellular signal-regulated protein kinases (ERKs), c-Jun NH(2)-terminal kinases, and p38 MAPK in cardiac myocytes. Oxyradical scavengers or Ca(2+) chelators inhibited DM-induced activation of ERKs and p38 MAPK. DM-induced activation of ERKs was also inhibited by overexpression of dominant negative mutants of Ras (D.N.Ras), and the p38 MAPK activation was attenuated by D.N.Rho. The number of DM-induced apoptotic cells was markedly increased when the ERK signaling pathway was selectively blocked by a specific MAPK/ERK kinase inhibitor, PD98059, whereas pretreatment with a specific inhibitor of p38 MAPK, SB203580, significantly reduced the amount of apoptosis. CONCLUSIONS: These results suggest that DM activates MAPKs through reactive oxygen species and Ca(2+) and that the MAPK family plays important roles in DM-induced apoptosis in cardiac myocytes. ERKs protect cardiomyocytes from apoptosis, whereas p38 MAPK is involved in the induction of cardiomyocyte apoptosis.
Animals↗
Embryonic lethality and defective neural tube closure in mice lacking squalene synthase.
Squalene synthase (SS) catalyzes the reductive head-to-head condensation of two molecules of farnesyl diphosphate to form squalene, the first specific intermediate in the cholesterol biosynthetic pathway. We used gene targeting to knock out the mouse SS gene. The mice heterozygous for the mutation (SS+/-) were apparently normal. SS+/- mice showed 60% reduction in the hepatic mRNA levels of SS compared with SS+/+ mice. Consistently, the SS enzymatic activities were reduced by 50% in the liver and testis. Nevertheless, the hepatic cholesterol synthesis was not different between SS+/- and SS+/+ mice, and plasma lipoprotein profiles were not different irrespective of the presence of the low density lipoprotein receptor, indicating that SS is not a rate-limiting enzyme in the cholesterol biosynthetic pathway. The mice homozygous for the disrupted SS gene (SS-/-) were embryonic lethal around midgestation. E9.5-10.5 SS-/- embryos exhibited severe growth retardation and defective neural tube closure. The lethal phenotype was not rescued by supplementing the dams either with dietary squalene or cholesterol. We speculate that cholesterol is required for the development, particularly of the nervous system, and that the chorioallantoic circulatory system is not mature enough to supply the rapidly growing embryos with maternal cholesterol at this developmental stage.
Animals↗
Karyotypic analyses of hepatoblastoma. Report of two cases and review of the literature suggesting chromosomal loci responsible for the pathogenesis of this disease.
Two cases of fetal hepatoblastoma with unique karyotypic changes are described. One was a 17-month-old boy with multiple unbalanced chromosomal translocations, resulting in four types of derivative chromosomes involving chromosomal loci at 1q21, 1q32, 2q23, 6q27, 7p22, and 21p12, partial tetrasomy of 1q, partial trisomy of 2q, and partial monosomy of 21p. The clonal karyotype of this tumor was 46,XY,der(2)t(1;2)(q32;q37), der(6)t(1;6)(q12;q27), der(7)t(2;7)(q23;p22), der(21)t(2;21) (q23;p12). In the other case, a 4-year-old girl, karyotypic analyses revealed trisomy 2 and 8, and the clonal karyotype of this case was 48,XX,+2,+8. Review of these cases together with previous reports suggested the significance of chromosomal changes including numerical abnormalities of 1q, 2(or 2q), 20, and 8 (or 8q), and breakage of 1q and 2q in the development of hepatoblastoma. The results presented herein underscore the significance of numerical abnormalities of chromosomal regions 1q and 2q and of chromosome 8 in the development of hepatoblastoma, in addition to abnormalities of 6q27, 7p22, and 21p12-13 as other chromosomal loci that may be responsible for the pathogenesis of this embryonal type of tumor.
Child, Preschool↗
D-amino acid formation induced by a chiral field within a human lens protein during aging.
We have previously shown that Asp-151 in alphaA-crystallin from aged human lens are converted to the biologically uncommon D-isomer to a high degree, showing that the formation of D-isomer was not simple racemization, but stereoinvertion. This suggests that alphaA-crystallin has a chiral reaction field which promotes the inversion of L-Asp to D-Asp residues in the native higher order structure of alphaA-crystallin itself. Here, we show that when the aged human alphaA-crystallin, enriched at Asp-151 with the D-isomer (D/L ratio of 5.7), was unfolded by heating at 70 degrees C or 6 M urea, the D-Asp-151 in the unfolded alphaA-crystallin was rapidly racemized (D/L ratio of 2.17 to 1.21). This presumably reflects a relaxation of the chiral field that was initially inducing the stereoinversion from the natural L-isomer to the D-isomer.
Aged↗
Telomerase activity in central nervous system malignant lymphoma.
BACKGROUND: Primary central nervous system malignant lymphoma (PCNSL) has been regarded as a rare neoplasm. Recently, however, its incidence has been rapidly increasing. Despite active clinical trials, its clinical and biologic features remain unknown and there has been no effective treatment or prognostic factor. The current study attempted to elucidate telomerase activity and expression of the telomere-related RNA of PCNSL as novel prognostic factors. METHODS: The subjects were 12 patients with histologically diagnosed PCNSL. All patients were treated with chemoradiotherapy consisting of whole-brain radiation, vincristine, etoposide, and prednisolone. Telomerase activity in the resected tumor was analyzed both qualitatively and quantitatively using the TRAP (telomeric amplification assay protocol)/TRAP-HPA (hybridization protection assay) method. The expression of telomere-related RNA (hTERT, hTERC, and TEP1) was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: Telomerase activity was detected in 10 of 12 patients with PCNSL, with an average activity of 148.9 relative light units. The average telomere length was 5.55 kb. The expression of hTERT correlated with telomerase activity, and there was a statistically significant correlation between telomerase activity and both the duration of survival and the interval to tumor progression. CONCLUSIONS: Telomerase activity and the expression of hTERT may be novel prognostic factors in patients with PCNSL.
Adult↗
A single nuclear transcript encoding mitochondrial RPS14 and SDHB of rice is processed by alternative splicing: common use of the same mitochondrial targeting signal for different proteins.
The rice mitochondrial genome has a sequence homologous to the gene for ribosomal protein S14 (rps14), but the coding sequence is interrupted by internal stop codons. A functional rps14 gene was isolated from the rice nuclear genome, suggesting a gene-transfer event from the mitochondrion to the nucleus. The nuclear rps14 gene encodes a long N-terminal extension showing significant similarity to a part of mitochondrial succinate dehydrogenase subunit B (SDHB) protein from human and a malarial parasite (Plasmodium falciparum). Isolation of a functional rice sdhB cDNA and subsequent sequence comparison to the nuclear rps14 indicate that the 5' portions of the two cDNAs are identical. The sdhB genomic sequence shows that the SDHB-coding region is divided into two exons. Surprisingly, the RPS14-coding region is located between the two exons. DNA gel blot analysis indicates that both sdhB and rps14 are present at a single locus in the rice nucleus. These findings strongly suggest that the two gene transcripts result from a single mRNA precursor by alternative splicing. Protein blot analysis shows that the size of the mature RPS14 is 16.5 kDa, suggesting removal of the N-terminal 22.6-kDa peptide region. Considering that the rice mitochondrial genome lacks the sdhB gene but contains the rps14-related sequence, transfer of the sdhB gene seems to have occurred before the transfer of the rps14 gene. The migration of the mitochondrial rps14 sequence into the already existing sdhB gene could bestow the capacity for nuclear expression and mitochondrial targeting.
Alternative Splicing↗
Cytogenetic alterations in pituitary adenomas detected by comparative genomic hybridization.
Pituitary adenomas are benign monoclonal tumors that are either hormonally functional or nonfunctional. Although their histologic and immunocytologic characteristics have been studied extensively, cytogenetic studies are scarce. We have investigated the cytogenetic alterations and DNA ploidy patterns of 12 sporadic pituitary adenomas, including 2 growth-hormone-secreting tumors, 1 prolactinoma, and 9 nonfunctional adenomas, by comparative genomic hybridization (CGH) and laser scanning cytometry (LSC). CGH revealed that the mean number of sites of copy gain was significantly higher in functioning adenomas than in nonfunctioning tumors (P < 0.01). The most frequent change detected was loss of 13q (5 cases), with a minimal common overlapping region at 13q14. These findings suggest that a putative tumor suppressor gene on 13q14 may play an important role in the development of pituitary adenomas. DNA aneuploidy was detected by LSC in 3 of the 12 cases. The DNA aneuploid adenomas showed cytogenetic changes more frequently than did the DNA diploid tumors (P < 0.02).
Adenoma↗
Heart-specific activation of LTK results in cardiac hypertrophy, cardiomyocyte degeneration and gene reprogramming in transgenic mice.
Leukocyte tyrosine kinase (LTK) is a receptor-type protein tyrosine kinase belonging to the insulin receptor superfamily. To elucidate its biological role, we generated transgenic mice expressing LTK under the control of cytomegarovirus enhancer and beta-actin promoter. The transgenic mice exhibited growth retardation and most of the transgenic mice died within several months after birth. Interestingly, although LTK was expressed in several major organs, the activation (tyrosine-phosphorylation, kinase activity, and multimerization) of LTK was observed selectively in the heart, where LTK was localized on intracellular membrane, presumably on endoplasmic reticulum. Echocardiography showed that the transgenic heart underwent severe concentric hypertrophy, which resulted in reduced cardiac output, low blood pressure, and increased heart rate. Histological examination of the heart exhibited focal degeneration of cardiomyocytes. These histological changes were considered to be due to apoptosis, based on the finding that the sarcolemmas of the degenerative cardiomyocytes were well preserved. In addition, expression of fetal genes, such as atrial natriuretic peptide and skeletal alpha-actin, was markedly induced in the transgenic heart. These results indicate that a certain tissue-specific mechanism of activating LTK exists in the heart and that the activated LTK resulted in cardiac hypertrophy, cardiomyocyte degeneration and gene reprogramming. These findings will provide novel insights into the activating mechanism and biological role of LTK in vivo.
Animals↗
Coronary blood flow velocity in normal infants and young adults assessed by transthoracic echocardiography.
The present study has demonstrated that it is possible to measure blood flow of the coronary artery in children using transthoracic 2-dimensional Doppler echocardiography. This is the first study on the relations between coronary flow velocity and age and heart rate in normal subjects.
Adolescent↗
Relation of atrial size and function to Doppler indexes of diastolic function in normal human fetuses.
Fetal atrial function is compared with diastolic ventricular function indexes. The falloff of hyperfunction in fetal atrial contraction patterns matches sequentially the lessening of A wave dominance in the Doppler filling patterns for both ventricles.
Age Factors↗
Effects of ginseng saponins on responses induced by various receptor stimuli.
We investigated the effects of four ginseng saponins, ginsenoside-Rb1, -Rg2, -Rg3 and -Ro, on the responses induced by receptor stimulation of various stimuli. Ginsenoside-Rg2 (1-100 microM) reduced the secretions of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine and gamma-aminobutyric acid but not by angiotensin II, bradykinin, histamine and neurotensin. In guinea-pig, the ginsenoside also diminished the nicotine-induced secretion of catecholamines from the adrenal chromaffin cells, but it did not affect the muscarine- and the histamine-induced ileum contractions. On the other hand, ginsenoside-Rg3 (1-100 microM) reduced not only the acetylcholine-, the gamma-aminobutyric acid- and the neurotensin-induced secretions but also, at a higher concentration (100 microM), the angiotensin II-, the bradykinin- and the histamine-induced secretions from the bovine chromaffin cells. Furthermore, the saponin (3-100 microM) significantly inhibited the muscarine- and the histamine-induced ileum contractions of the guinea-pig. Ginsenoside-Rb1 and -Ro had no marked effect on their responses. These results strongly suggest that ginsenoside-Rg2 is a potent selective blocker of nicotinic acetylcholine and gamma-aminobutyric acid receptors (ionotropic receptors) and ginsenoside-Rg3 is not only a blocker of ionotropic receptors but also an antagonist of muscarinic or histamine receptors.
Adrenal Glands↗
Vascular injury causes neointimal formation in angiotensin II type 1a receptor knockout mice.
Many studies using small-animal models suggest that angiotensin II (Ang II) plays an important role in neointimal formation after vascular injury. In the present study, we examined whether Ang II type 1 receptor (AT1)-mediated Ang II signaling is indispensable for the development of injury-induced neointimal formation using AT1a knockout (KO) mice. Reverse transcriptase-polymerase chain reaction analysis revealed that AT1 mRNA was not detectable in both uninjured and injured carotid arteries of KO mice, whereas the AT1 gene was expressed in uninjured carotid arteries of wild-type (WT) mice. At 14 days after injury, AT1 mRNA levels were increased by 1.5-fold in injured arteries of WT mice. Although AT2 mRNA was not detectable in uninjured arteries, expression of AT2 gene was induced in both animal groups at 2 weeks after injury. Vascular injury induced neointimal formation in KO mice as well as in WT mice. There were no significant differences between WT and KO mice in the extent of histological findings such as increased cross-sectional areas of the neointima and the media, the number of proliferating smooth muscle cells, and the amount of collagen and fibronectin. Treatment with subpressor doses of Ang II after injury enhanced the growth of neointima in WT mice but not in KO mice. Moreover, treatment with the selective AT1 antagonist CV-11974 before injury significantly decreased the formation of neointima in only WT mice, whereas treatment with the selective AT2 antagonist PD-123319 before injury had no effects in both animal groups. These results suggest that AT1-mediated Ang II signaling is not essential for the development of neointimal formation, although it may modify it.
Analysis of Variance↗