Search PubMed⌕ Search

Biomedical subjects

H Abe

Publications and source records attributed to H Abe.

At least 325 records · Page 18Linked to original sources

A multifunctional transcription factor (A1p145) regulates the smooth muscle phenotype in mesangial cells.

A1p145, a novel DNA binding protein for type IV collagen gene (COL4), has multiple functions including DNA replication factor C and DNA binding for several other genes. To elucidate the mechanisms underlying the differentiation process of mesangial cells (MCs), we investigated the effects of A1p145 on rat MCs. Cells in the early passages showed a smooth muscle-like phenotype such as low cell turnover, high levels of expression for COL4, and smooth muscle alpha-actin (SMA). Cells in the late passages lost their phenotype. The amount of binding activity to COL4 promoter was inversely correlated with the level of COL4 mRNA. Introduction of antisense for A1p145 into late passage cells enhanced the levels of mRNA for COL4 and SMA. The levels of proliferating cell nuclear antigen mRNA were also suppressed. These results suggest that A1p145 is a negative transcription factor for COL4 and may be a phenotypic modulator.

Actins↗

Role of basic fibroblast growth factor in the pathogenesis of moyamoya disease.

The pathogenesis of moyamoya disease is still under investigation. In this study, the authors focus on the role of cytokines in the pathogenesis of moyamoya disease by using immunohistochemical analyses. The authors examined two specimens in the circle of Willis obtained at autopsy from two patients with moyamoya disease and two additional specimens obtained from control cadavers with atherosclerotic stenosis of the intracranial carotid arteries. Immunohistochemical examinations of the sections of the major intracranial arteries were performed using antismooth muscle cells (SMCs), monocytes, growth factor, cell nuclear antigen, and fragmented DNA antibodies. Basic fibroblast growth factor (bFGF) staining was present only in the endothelial cells of the moyamoya disease specimens and was not seen in control samples. In addition, the endothelial cells and SMCs in the media were positive for terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick-end labeling of fragmented DNA method but not in the SMCs in the intima in moyamoya disease specimens, which indicates that an apoptotic process is active in only SMCs in the media but not in the intima. In conclusion, it is suggseted that the presence of bFGF in the media specifically seen in moyamoya disease suppresses the apoptotic process of SMCs in the intima.

Journal Article↗

Cerebellar microfolia and other abnormalities of neuronal growth, migration, and lamination in the Pit1dw-J homozygote mutant mouse.

The Snell dwarf mouse (Pit1dw-J homozygote) has a mutation in the Pit1 gene that prevents the normal formation of the anterior pituitary. In neonates and adults there is almost complete absence of growth hormone (GH), prolactin (PRL), thyroxin (T4), and thyroid-stimulating hormone (TSH). Since these hormones have been suggested to play a role in normal development of the central nervous system (CNS), we have investigated the effects of the Pit1dw-J mutation on the cerebellum and hippocampal formation. In the cerebellum, there were abnormalities of both foliation and lamination. The major foliation anomalies were 1) changes in the relative size of specific folia and also the proportional sizes of the anterior vs posterior cerebellum; and 2) the presence of between one and three microfolia per half cerebellum. The microfolia were all in the medial portion of the hemisphere in the caudal part of the cerebellum. Each microfolium was just rostral to a normal fissure and interposed between the fissure and a normal gyrus. Lamination abnormalities included an increase in the number of single ectopic granule cells in the molecular layer in both cerebellar vermis (86%) and hemisphere (40%) in comparison with the wild-type mouse. In the hippocampus of the Pit1dw-J homozygote mouse, the number of pyramidal cells was decreased, although the width of the pyramidal cell layer throughout areas CA1-CA3 appeared to be normal, but less densely populated than in the wild-type mouse. Moreover, the number of granule cells that form the granule cell layer was decreased from the wild-type mouse and some ectopic granule cells (occurring both as single cells and as small clusters) were observed in the innermost portion of the molecular layer. The abnormalities observed in the Pit1dw-J homozygote mouse seem to be caused by both direct and indirect effects of the deficiency of TSH (or T4), PRL, or GH rather than by a direct effect of the deletion of Pit1.

Animals↗

Circadian oscillation of BMAL1, a partner of a mammalian clock gene Clock, in rat suprachiasmatic nucleus.

A superfamily gene which encodes a bHLH (basic helix-loop-helix)/PAS transcription factor, BMAL1, was cloned and sequenced from rat cDNA. A robust circadian rhythm of rat BMAL1 expression was detected by in situ hybridization in the suprachiasmatic nucleus (SCN), the site of the circadian clock, with the highest level at the subjective night. Less prominent and completely reversed circadian rhythms of rBMAL1 mRNA were observed in the piriform and parietal cortices. The hybridization signals of rBMAL1 mRNA were also detected in the olfactory bulb, hippocampus, and cerebellum. Since the product of rBMAL1 was recently demonstrated to dimerize with the protein of a mammalian clock gene, Clock, and the protein complex was shown to bind the E Box in the promoter region of mPer1 (a mouse homologue to Drosophila clock gene, Per), rBMAL1 possibly plays a critical role in the clock mechanism generating the circadian oscillation in rats.

ARNTL Transcription Factors↗

Combined chemotherapy and radiation therapy for central nervous system germ cell tumors: preliminary results of a Phase II study of the Japanese Pediatric Brain Tumor Study Group.

The authors conducted a multiinstitutional phase II study to establish a postsurgical combined chemotherapy and radiation therapy regimen for patients with primary germ cell tumors of the brain. After surgical debulking of the tumor and histological verification, patients were divided into three therapeutic groups: good prognosis, intermediate prognosis, and poor prognosis. Patients received two kinds of chemotherapy (three courses) prior to receiving radiation therapy: carboplatin-etoposide combination ([CARB-VP]: carboplatin 450 mg/m(2) on Day 1, etoposide 150 mg/m(2) on Days 1-3) or ifosphamide-cisplatin-etoposide combination ([ICE]: ifosphamide 900 mg/m(2), cisplatin 20 mg/m(2), and etoposide 60 mg/m(2) on Days 1-5). Patients in the good prognosis group (those with germinomas) were treated with CARB-VP followed by local radiation therapy (24 Gy). Patients in the intermediate prognosis group received CARB-VP followed by local radiation therapy (50 Gy); they received five additional chemotherapy treatments. Patients in the poor prognosis group received ICE followed by whole craniospinal radiation therapy; they also received five additional chemotherapy treatments. Eighty-two patients were evaluated. For the 56 patients with germinomas, a 93% rate of complete remission after treatment was achieved. The remission rate was 76% for 21 patients in the intermediate prognosis group, and no recurrence was detected during a median follow-up period of 2.6 years. In the group of five patients with poor prognosis, the disease in three patients progressed during chemotherapy or radiation therapy and they died within 6 months. There were no serious complications in the surviving patients. The authors found their treatment protocols to be currently effective for patients with germinomas and those with an intermediate prognosis.

Journal Article↗

Occult neurohypophyseal germinomas in patients presenting with central diabetes insipidus.

Although neurohypophyseal germinoma is known be a common initial symptom in cases of diabetes insipidus (DI), its radiological detection may take months or years even by a high-resolution magnetic resonance (MR) imaging. The term "occult neurohypophyseal germinoma" denotes such cases, but its clinical picture remains obscure. Of seven patients with neurohypophyseal germinoma presenting with DI during the last 5 years, three patients showed no evidence of tumor at the onset of DI and were treated as "idiopathic" DI. Neurohypophyseal germinoma was eventually diagnosed in these three patients as the tumor became evident on sequential MR imaging studies and the patients were successfully treated with chemotherapy and radiation therapy. To delineate the clinical features of the occult neurohypophyseal germinoma, the authors analyzed endocrinological aspects and MR images in these patients and compared them with those in two patients with true idiopathic DI and four patients with overt neurohypophyseal germinoma and DI. Nine previously reported cases in the literature were reviewed. During the stage at which the germinoma gave no notable change on MR images, patients often displayed anterior pituitary dysfunction, particularly growth hormone (GH) deficiency, or an elevation of serum or cerebrospinal fluid human chorionic gonadotropin-beta. Preceding the appearance of an obvious tumor mass, a slight swelling of the pituitary stalk with loss of normal hyperintensity of the posterior pituitary lobe was a common finding on MR imaging. Central DI associated either with an enlarged stalk, decreased GH secretion, or an elevated serum human chorionic gonadotropin-beta should prompt the diagnosis of an occult germinoma.

Journal Article↗

Inhibition of hypoxia-inducible factor 1 activity by nitric oxide donors in hypoxia.

Nitric oxide (NO) is known to have various biologic and pathophysiologic effects on organisms. The molecular mechanisms by which NO exerts harmful effects are unknown, although various O2 radicals and ions that result from reactivity of NO are presumed to be involved. Here we report that adaptive cellular response controlled by the transcription factor hypoxia-inducible factor 1 (HIF-1) in hypoxia is suppressed by NO. Induction of erythropoietin and glycolytic aldolase A mRNAs in hypoxically cultured Hep3B cells, a human hepatoma cell line, was completely and partially inhibited, respectively, by the addition of sodium nitroprusside (SNP), which spontaneously releases NO. A reporter plasmid carrying four hypoxia-response element sequences connected to the luciferase structural gene was constructed and transfected into Hep3B cells. Inducibly expressed luciferase activity in hypoxia was inhibited by the addition of SNP and two other structurally different NO donors, S-nitroso-L-glutathione and 3-morpholinosydnonimine, giving IC50 values of 7.8, 211, and 490 microM, respectively. Inhibition by SNP was also observed in Neuro 2A and HeLa cells, indicating that the inhibition was not cell-type-specific. The vascular endothelial growth factor promoter activity that is controlled by HIF-1 was also inhibited by SNP (IC50 = 6.6 microM). Induction generated by the addition of cobalt ion (this treatment mimics hypoxia) was also inhibited by SNP (IC50 = 2.5 microM). Increased luciferase activity expressed by cotransfection of effector plasmids for HIF-1alpha or HIF-1alpha-like factor in hypoxia was also inhibited by the NO donor. We also showed that the inhibition was performed by blocking an activation step of HIF-1alpha to a DNA-binding form.

Cell Hypoxia↗

Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1.

Insulin resistance is often associated with atherosclerotic diseases in subjects with obesity and impaired glucose tolerance. This study examined the effects of insulin resistance on coronary risk factors in IRS-1 deficient mice, a nonobese animal model of insulin resistance. Blood pressure and plasma triglyceride levels were significantly higher in IRS-1 deficient mice than in normal mice. Impaired endothelium-dependent vascular relaxation was also observed in IRS-1 deficient mice. Furthermore, lipoprotein lipase activity was lower than in normal mice, suggesting impaired lipolysis to be involved in the increase in plasma triglyceride levels under insulin-resistant conditions. Thus, insulin resistance plays an important role in the clustering of coronary risk factors which may accelerate the progression of atherosclerosis in subjects with insulin resistance.

Animals↗

Functional characteristics and the complete primary structure of ascidian gelsolin.

The body wall of the ascidian is composed of unusual multi-nucleated smooth muscle cells enriched with thin actin filaments containing troponin-tropomyosin which run along the longitudinal cell axis without being organized into striated structures. We purified an actin-binding protein of 80 kDa, tentatively termed 80K protein, from the body wall muscle of ascidian, Halocynthia roretzi, and characterized the functional properties and molecular structures. In the presence of Ca2+, the 80K protein accelerated the initial phase of actin polymerization, namely the nucleation process, decreased the level of polymerization at the steady state, caused marked reduction in viscosity of an F-actin solution, and fragmented F-actin filaments, while in the absence of Ca2+, it remained associated with F-actin without severing the filaments. The interaction of the 80K protein with actin was inhibited by phosphatidylinositol 4,5-bisphosphate (PIP2). When actin was polymerized in the presence of acrosome actin bundles from horseshoe crab sperm, the 80K protein inhibited the growth of actin filaments at the barbed end but not at the pointed end, indicating that the 80K protein functions as a barbed-end capping protein. In order to characterize the molecular structure of the 80K protein, cDNAs encoding this protein were isolated from the lambda gt11 cDNA library of the ascidian muscle by using a monoclonal antibody (AS23) specific for this protein and the entire sequence was determined. The deduced peptide sequence showed about 44% homology in amino acid residues with the human gelsolin sequence, and in addition, 6 repeating segments were observed in the sequence of the 80K protein as has been described in the gelsolin sequence. These results indicate strongly that the 80K protein belongs to the gelsolin family.

Actins↗

ERD6, a cDNA clone for an early dehydration-induced gene of Arabidopsis, encodes a putative sugar transporter.

Previously, we constructed a cDNA library from Arabidopsis plants that were exposed to dehydration stress for 1 h and obtained the ERD6 clone. Here we report that the ERD6 cDNA consists of 1741 bp and encodes a polypeptide of 496 amino acids having a predicted molecular weight of 54,354. The putative polypeptide of ERD6 is related to those of sugar transporters of bacteria, yeasts, plants and mammals. Hydropathy analysis revealed that ERD6 protein has 12 putative transmembrane domains and a central hydrophilic region. Sequences that are conserved at the ends of the 6th and 12th membrane-spanning domains of sugar transporters are also present in ERD6. These data suggest that ERD6 encodes a sugar transporter. Genomic Southern blots indicate that the ERD6 gene is a member of a multigene family in the Arabidopsis genome. The expression of the ERD6 gene was induced not only by dehydration but also by cold treatment.

Amino Acid Sequence↗

Short alternative splice transcripts of the mdm2 oncogene correlate to malignancy in human astrocytic neoplasms.

The mdm2 oncogene encodes a 90-kDa nuclear phosphoprotein that binds and inhibits the function of the p53 tumor suppressor protein. It was recently reported that the expression of alternatively spliced variants of mdm2 correlated with malignancy in ovarian tumors and bladder carcinomas. We analyzed the presence of alternatively spliced mdm2 variants and studied their correlation to p53 status in a total of 66 human astrocytic tumors, including 32 glioblastomas multiforme, 17 anaplastic astrocytomas, 12 astrocytomas, and 5 pilocytic astrocytomas, using a specific nested reverse transcription-PCR technique. The full-length mdm2 transcript was demonstrated in all of the cases. Multiple-sized PCR products were found in 29 cases. Two of 5 pilocytic astrocytomas (40%), none of 12 astrocytomas, and 5 of 17 anaplastic astrocytomas (29%) showed alternative splice variants. In contrast, 22 of 32 glioblastomas (69%) showed the presence of splice variants, demonstrating a significantly higher frequency than in lower-grade astrocytomas (P < 0.0003). A majority of the splice variants were 707 base-type (mdm2-b), which was confirmed by sequence analysis. There was no apparent correlation of the presence of mdm2 splice variants with p53 gene status. These results suggest a new role for mdm2, independent of p53 gene status, as an oncogene in the development of malignant astrocytic tumors.

Alternative Splicing↗

Circadian release of amino acids in the suprachiasmatic nucleus in vitro.

Temporal patterns of release of aspartate, glutamate and glycine, which are related to excitatory amino acidergic transmission, were examined in organotypic slice cultures of rat suprachiasmatic nucleus over a 60 h period. Vasopressin release in the same culture was measured simultaneously to compare the temporal pattern with that of the amino acids. Amino acids and vasopressin were measured by high performance liquid chromatography and enzyme immunoassay, respectively. Robust circadian rhythms were detected in release of aspartate, glutamate and glycine. Glycine levels were about 10 times higher than those of aspartate and glutamate in the culture. Vasopressin also showed a clear circadian rhythm and the phase angle difference between each amino acid and AVP was not significantly different. The results indicate that cultured SCN cells release these amino acids and the release is under the control of the circadian pacemaker.

Animals↗

Three-dimensional scanning electron microscopic study of keratoconus corneas.

OBJECTIVE: To examine the 3-dimensional collagen fibril organization in the Bowman layer of keratoconus corneas. METHODS: Eight keratoconus corneas, 8 corneas with other diseases, and 5 normal human corneas were studied. A cell maceration method in combination with scanning electron microscopy was used to examine the collagen network in the Bowman layer. RESULTS: In normal corneas, the surface of the Bowman layer was smooth and collagen fibrils were regularly arranged. By contrast, sharply edged defects in the Bowman layer were found in keratoconus corneas. Lattice-like configurations of the ruptured Bowman layer and collagenous scar tissue were observed, to varying degrees, in all keratoconus corneas examined. None of the other diseased corneas exhibited the ruptures. CONCLUSIONS: Scanning electron microscopy demonstrated alterations in the Bowman layer specific to keratoconus. Fragmentation of the Bowman layer may be an early change leading to keratoconus conditions.

Adolescent↗

High-Resolution Terahertz Spectroscopy by a Compact Radiation Source Based on Photomixing with Diode Lasers in a Photoconductive Antenna

We demonstrate generation of continuous-wave terahertz radiation and its application to molecular spectroscopy. The radiation source is based on the photomixing of two diode laser beams in a low-temperature-grown GaAs photoconductive antenna, which offered output power of several tens of nanowatts at frequencies up to 2 THz with its long term frequency stability being about 5 MHz. The pure rotational spectra of CH3CN and isotopomers of CO were measured with this source, and 1% of absorption was clearly detected with a simple amplitude modulation technique. This indicates that the present system has a potential capability for high-resolution and high-sensitivity molecular spectroscopy. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗

Free D- and L-amino acids in ventricular cerebrospinal fluid from Alzheimer and normal subjects.

Free D-Ser, D-Asp and total D-amino acids were significantly higher (p < 0.05) in Alzheimer (AD) ventricular CSF than in normal CSF. There was no significant difference in the total L-amino acids between AD and normal CSF, but L-Gln and L-His were significantly higher (p < 0.05) in AD-CSF. The higher concentrations of these D- and L-amino acids in AD ventricular CSF could reflect the degenerative process that occurs in Alzheimer's brain since ventricular CSF is the repository of amino acids from the brain.

Alzheimer Disease↗

Resting 123I-BMIPP scintigraphy in diagnosis of effort angina pectoris with reference to subsets of the disease.

This study was undertaken to assess the diagnostic value of resting 123I-BMIPP scintigraphy in patients with effort angina pectoris. One hundred and four patients underwent scintigraphic and angiographic examinations. The subsets of the patients were stable effort angina pectoris (stable type) in 27 cases, new onset of effort angina pectoris (new onset type) in 21 cases, and worsening effort angina pectoris (worsening type) in 35 cases. The remaining 21 cases were subjects without evidences of coronary artery disease (non-CAD). 123I-BMIPP was injected under resting and pain free condition, then data for single photon emission tomography (SPECT) were acquired. The positive regional 123I-BMIPP defects in three coronary territories were visually judged on the tomographic images. The overall sensitivity to diagnose the patients was 62.6% (52/83) and the overall specificity to exclude non-CAD subjects was 95.2% (20/21). The detection rate in each subset of the disease was 48.1% (13/27) in stable type, 47.6% (10/21) in new onset type and 77.1% (27/35) in worsening type (p < 0.05 versus two other types). For detection of stenosed vessels, the overall sensitivity was 41.4% (56/148) and the overall specificity was 93.8% (152/164). The rate of detection of stenosed vessels was 31.7% (13/41) in stable type, 31.4% (11/35) in new onset type, and 55.6% (40/72) in worsening type (p < 0.05 versus two other types). Vessels with 75% stenosis were more sensitively detected in the worsening type (33.3%; 4/12) compared to the remaining two types (8.3%; 1/12) even though the difference was not significant. The resting 123I-BMIPP scintigraphy was therefore valuable in diagnosing patients with effort angina pectoris and involved coronary arteries especially in the subset of patients with worsening type.

Aged↗

[A mitral valve reconstruction of infective endocarditis with brain abscess and intracranial mycotic aneurysm].

A case is reported of a brain abscess and an intracranial mycotic aneurysm associated with infective endocarditis caused by streptococcus intermedius. A 60-year-old man with a history of fever presented aphasia and right hemiparesis. A computed tomographic scan of the head revealed a low-density area with ring enhancement in the left parietal lobe consistent with a brain abscess. An angiography demonstrated an aneurysm on the distal branch of the middle cerebral artery compatible with a mycotic aneurysm. Doppler echo cardiography showed severe mitral regurgitation by chordal ruptures. The brain abscess and intracranial mycotic aneurysm were resolved under appropriate antibiotic therapy for eight weeks. Then, the mitral valve was reconstructed by replacement of the chordae tendineae with expanded polytetrafloroethylene suture and annuloplasty. The patient had no neurologic deficit except for paresthesia in the right hand, and had no mitral regurgitation at discharge.

Aneurysm, Infected↗