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Biomedical subjects

M Hirano

Publications and source records attributed to M Hirano.

At least 163 records · Page 9Linked to original sources
PubMed1999

Leber's hereditary optic neuropathy mitochondrial DNA mutations at nucleotides 11778 and 3460 in multiple sclerosis.

OBJECTIVES: Leber's hereditary optic neuropathy (LHON) can be difficult to distinguish from optic neuritis seen in multiple sclerosis (MS). About half of the LHON patients harbor a mutation at nucleotide (nt) 11778 in the mitochondrial (mt) DNA. In addition, mutations at nt-3460 and nt-14484 have been associated with LHON. An association of LHON and MS has been suspected for decades, and, recently, the LHON nt-11778 and nt-3460 mtDNA mutations have been found in several patients with MS or MS-like disease. We attempted to determine which MS patients should be evaluated further for LHON mutations. METHODS: We screened 103 clinically definite MS patients (age range from 18 to 72 years, 27 men and 76 women) for the LHON nt-11778 and nt-3460 mtDNA mutations. RESULTS: Neither mutation was identified in the patients. CONCLUSIONS: Our findings confirm previous reports which found that both LHON mutations are rare in unselected MS patients. The reports to date suggest that MS patients with peripapillary teleangiectasia typical of LHON, with relatives harboring LHON or with early severe bilateral optic neuropathy, particularly if female, should be further evaluated for LHON mutations.

Adolescent↗
PubMed1999

Electron microscopic and immunohistochemical investigation of Reinke's edema.

Examination was made of the vocal fold mucosa of Reinke's edema immunohistochemically and electron microscopically, with special attention to blood vessels in Reinke's space (RS). Ten surgical specimens of Reinke's edema were used, and the results obtained are summarized as follows. There were subepithelial vascularization and many dilated vessels in RS. The vessels had thin endothelium with many fenestrae, many vesicles, and a thickened basement membrane. Plasma exuded from the capillaries into surrounding tissue via fenestrae. These findings demonstrate increased permeability of the vessels. The vascular walls were thin, with few pericytes. The pericytes were situated away from the endothelial cells. Some endothelial cells and pericytes had degenerated, and vessel occlusion was apparent in some cases. These findings indicate the vessels had become fragile. Interstitial cells and/or inflammatory cells in RS showed stained cytoplasm with vascular endothelial growth factor. This growth factor may possibly enhance capillary permeability and form fragile vessels in RS. Fragility and alteration in permeability of the vessels are presumed to cause edema of RS, which may progress to Reinke's edema.

Capillaries↗
PubMed1999

Mutated alpha-synuclein gene in two Greek kindreds with familial PD: incomplete penetrance?

The G209A mutation in the alpha-synuclein gene has been associated with autosomal dominant PD (ADPD) in a family from Contursi, Italy, and three apparently unrelated Greek families. Several groups around the world failed to identify the G209A mutation in a sizable series of familial and sporadic cases of PD. The authors present two additional Greek families with ADPD associated with the G209A mutation. In both families, asymptomatic carriers older than the expected age at onset were found.

Adult↗
PubMed1999

Autobiographical recollection and affects of cues in an amnesic patient.

The individual described herein (Y.K.) is a pure amnesic patient with severe anterograde amnesia and a selective loss of specific personal episodes in his remote memories. In this study, we examined whether more concrete cues could elicit specificity in his autobiographical memory. It was found that the richness of his autobiographical memory under the condition with probes was significantly higher than condition without probes, although Y.K.'s performance on recalling autobiographical memory was inferior to that of control subjects under both conditions. These results and our previous findings indicate that neither the disorder at the level of the framework's thematic retrieval nor the destruction of individual traces will account for the loss of Y.K.'s autobiographical memory. We suspect that Y.K.'s loss of autobiographical memory may be due to problems in the interface between thematic retrieval frameworks and individual traces.

Affect↗
PubMed1999

Activation of Ca(2+)-dependent K(+) current by nordihydroguaiaretic acid in porcine coronary arterial smooth muscle cells.

The effects of nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor and an antioxidant, on membrane currents were examined in single smooth muscle cells isolated from porcine coronary artery. Spontaneous transient outward currents (STOCs) recorded at -30 mV were markedly enhanced by NDGA (>/=10 microM). Pretreatment with caffeine and ryanodine abolished STOCs and reduced NDGA-induced increase in outward current at -30 mV by approximately 60%. NDGA showed dual action on an outward current elicited by step depolarization from -60 to 0 mV: inhibition and enhancement at concentrations of 3 and >/=10 microM, respectively. In the presence of Cd(2+), the inhibition of outward current by NDGA disappeared and the enhancement remained. NDGA inhibited both the voltage-dependent Ca(2+) channel current (IC(50) = 2.5 microM) and the delayed rectifier K(+) current (IC(50) = 9.8 microM). The NDGA-induced enhancement of STOCs and outward currents on depolarization was abolished by 100 nM iberiotoxin but was not affected by glibenclamide or apamin. Under current clamp mode, 30 microM NDGA significantly hyperpolarized myocytes. The application of lipoxygenase inhibitors (caffeic acid and esculetin), a cyclooxygenase inhibitor (indomethacin), antioxidants (ascorbic acid and erythorbic acid), and structural-related compounds of NDGA (catechol and dopamine) did not enhance K(+) currents. These results indicate that the opening of the large conductance Ca(2+)-dependent K(+) channel by NDGA, which is independent of its lipoxygenase inhibition or antioxidant effect, results in membrane hyperpolarization.

Animals↗
PubMed1999

[Evaluation of cytarabine-induced apoptosis in leukemic cell lines; utility of annexin V method].

Apoptosis is a morphologically and biochemically distinct form of cell death that occurs under a variety of physiological and pathological conditions. In the present study, using leukemic cell lines, time course of cytarabine-induced apoptosis was examined morphologically, using annexin V method, TUNEL method and fluorometric assay for caspase-3 activity. Morphological changes characteristic of apoptosis were observed in U937 and HL60 cells after 4-hour incubation with cytarabine and progressively evident until 48-hour incubation, but rarely found in K562 cells. In annexin V method and assay for caspase-3 activity, changes accompanied by apoptosis could also be detected at 4-hour incubation with cytarabine, but in TUNEL method, they were not found until 24-hour incubation. The advantage of annexin V method which detects phosphatidylserine emerging on cell surface during the early course of apoptosis included simplicity and rapidity of the procedure and short time requirement for apoptosis to appear after incubation with cytarabine. Usefulness of annexin V method in a study of clinical samples was discussed.

Annexin A5↗
PubMed1999

[Cauda equina syndrome due to recurrent malignant lymphoma of the spinal cord. A case report].

A 50-year-old man noticed a mass in the right cervical region and presented to our hospital. He underwent biopsy of a cervical lymph node, which revealed non-Hodgkin's lymphoma (diffuse large B cell, lymphoblastic type) histologically. He was treated with chemotherapy (CHOP) and radiation, and achieved complete remission. Two months later, he was admitted because of distal pain and extensive numbness of the lower limb as well as weakness of the left leg. Lumbar MRI showed an area of abnormal intensity in the cauda equina. Cytological examination of cerebrospinal fluid showed class V (lymphoma cells), so he was diagnosed as having recurrent malignant lymphoma of the spinal cord. He was treated with intrathecal chemotherapy and irradiation. After the treatment the mass in the cauda equina disappeared and the neurological symptoms in his legs resolved. It is rare for malignant lymphoma to recur in the spinal cord, particularly the cauda equina. It is well known that cauda equina syndrome can be caused by vertebral lesions and primary spinal cord tumors, but it is also necessary to keep malignant lymphoma of the cauda equina in mind.

Aged↗
PubMed1999

Space flight modulates signal transduction pathway of growth factor receptors in rat osteoblasts.

Bone metabolism is regulated by the balance of bone formation and resorption. Osteoblasts serves primarily for bone formation. Microgravity deteriorates osteoblastic function and inhibit bone formation. Growth factors regulate osteoblast function via receptors. Binding of EGF and PDGF to the receptors activates receptor tyrosine kinase and rapid association of adapter proteins Shc and Grb2, and evokes the Ras/MAP kinase cascade. Signals from various chemical and physical stimuli are transmitted to the nucleus, and induce c-fos and c-jun gene expression. However, effects of microgravity on the molecular events in osteoblasts remain unknown. The purpose of this study is to investigate the mRNA levels for PDGF-beta receptor, EGF receptor, Shc, and c-fos in rat osteoblasts during space flight.

Animals↗
PubMed1998

A novel plasmid recombination mechanism of the marine cyanobacterium Synechococcus sp. PCC7002.

We describe a novel mechanism of site-specific recombination in the unicellular marine cyanobacterium Synechococcus sp. PCC7002. The specific recombination sites on the smallest plasmid pAQ1 were localized by studying the properties of pAQ1-derived shuttle-vectors. We found that a palindromic element, the core sequence of which is G(G/A)CGATCGCC, functions as a resolution site for site-specific plasmid recombination. Furthermore, site-directed mutagenesis analysis of the element show that the site-specific recombination in the cyanobacterium requires sequence specificity, symmetry in the core sequence and, in part, the spacing between the elements. Interestingly, this element is over-represented not only in pAQ1 and in the genome of the cyanobacterium, but also in the accumulated cyanobacterial sequences from Synechococcus sp. PCC6301, PCC7942, vulcanus and Synechocystis sp. PCC6803 within GenBank and EMBL databases. Thus, these findings strongly suggest that the site-specific recombination mechanism based on the palindromic element should be common in these cyanobacteria.

Cyanobacteria↗
PubMed1998

Restricted photorelease of biologically active molecules near the plasma membrane.

An evanescent wave of ultraviolet light was successfully used to release biologically active molecules from caged compounds in living cells. The evanescent wave was generated by the total internal reflection in a limited region near the plasma membrane attached to the illuminated interface. At first, the photolysis efficiency of the evanescent wave of ultraviolet laser light was studied using caged glutamic acid in vitro. Then, caged Ca2+ introduced in the living cultured cell was similarly photolyzed by the evanescent wave and the resulting elevations of the concentration of intracellular Ca2+ in the proximity of the plasma membrane and in the cytosol were observed with a simultaneously introduced fluorescent calcium indicator. Inositol trisphosphate can also be photoreleased near the plasma membrane, which enables study of the temporal and spatial pathways of signal transduction. The method developed here provides a useful tool for studying signal transduction near the plasma membrane in a living cell.

Aniline Compounds↗
PubMed1998

ATP-dependent aggregation of single-stranded DNA by a bacterial SMC homodimer.

SMC (structural maintenance of chromosomes) proteins are putative ATPases that are highly conserved among Bacteria, Archaea and Eucarya. Eukaryotic SMC proteins are implicated in a diverse range of chromosome dynamics including chromosome condensation, dosage compensation and recombinational repair. In eukaryotes, two different SMC proteins form a heterodimer, which in turn acts as the core component of a large protein complex. Despite recent progress, no ATP-dependent activity has been found in individual SMC subunits. We report here the first biochemical characterization of a bacterial SMC protein from Bacillus subtilis. Unlike eukaryotic versions, the B.subtilis SMC protein (BsSMC) is a simple homodimer with no associated subunits. It binds preferentially to single-stranded DNA (ssDNA) and has a ssDNA-stimulated ATPase activity. In the presence of ATP, BsSMC forms large nucleoprotein aggregates in a ssDNA-specific manner. Proteolytic cleavage of BsSMC is changed upon binding to ATP and ssDNA. The energy-dependent aggregation of ssDNA might represent a primitive type of chromosome condensation that occurs during segregation of bacterial chromosomes.

Adenosine Triphosphatases↗
PubMed1998

Phosphorylation and activation of 13S condensin by Cdc2 in vitro.

13S condensin is a multisubunit protein complex essential for mitotic chromosome condensation in Xenopus egg extracts. Purified 13S condensin introduces positive supercoils into DNA in the presence of topoisomerase I and adenosine triphosphate in vitro. The supercoiling activity of 13Scondensin was regulated by mitosis-specific phosphorylation. Immunodepletion, in vitro phosphorylation, and peptide-mapping experiments indicated that Cdc2 is likely to be the kinase that phosphorylates and activates 13S condensin. Multiple Cdc2 phosphorylation sites are clustered in the carboxyl-terminal domain of the XCAP-D2 (Xenopus chromosome-associated polypeptide D2) subunit. These results suggest that phosphorylation of 13Scondensin by Cdc2 may trigger mitotic chromosome condensation in vitro.

Adenosine Triphosphatases↗
PubMed1998

Mitochondria in neuromuscular disorders.

This review considers primary mitochondrial diseases affecting the respiratory chain. As diseases due to mitochondrial DNA defects defy traditional anatomical classifications, we have not limited our discussion to neuromuscular disorders, but have extended it to include mitochondrial encephalomyopathies. Primary mitochondrial diseases can be due to mutations in either the nuclear or the mitochondrial genome. Nuclear mutations can affect (i) genes encoding enzymatic or structural mitochondrial proteins; (ii) translocases; (iii) mitochondrial protein importation; and (iv) intergenomic signaling. We review briefly recent molecular data and outstanding questions regarding these mendelian disorders, with special emphasis on cytochrome c oxidase deficiency and coenzyme Q10 deficiency. Mitochondrial DNA mutations fall into three main categories: (i) sporadic rearrangements (deletions/duplications); (ii) maternally inherited rearrangements (duplications); and (iii) maternally inherited point mutations. We summarize the most common clinical presentations and discuss pathogenic mechanisms, which remain largely elusive. Uncertainties about pathogenesis extend to the process of cell death, although excitotoxicity in neurons and apoptosis in muscle seem to have important roles.

Animals↗
PubMed1998

Two regions of the Mn-stabilizing protein from Synechococcus elongatus that are involved in binding to photosystem II complexes.

Limited proteolysis of the Mn-stabilizing protein (MSP) from the thermophilic cyanobacterium Synechococcus elongatus with chymotrypsin, trypsin or lysylendopeptidase that yielded four major polypeptides of 26 kDa, 22 kDa, 15 kDa and 11 kDa on denaturing gel electrophoresis resulted in total loss of the binding capacity of the protein to PSII complexes. Analyses of electrophoretic patterns and amino-terminal sequences of the proteolytic products revealed that the three proteases specifically cleaved the protein at a site between Phe156 and Gly163 or between Arg184 and Ser191. Site-directed mutagenesis was used to construct two mutant MSPs that had a nick between Phe156 and Leu157, a chymotrypsin-cleavage site, and Met before Leu157 or in place of Leu157. The two mutant proteins failed to bind to PSII complexes, although they largely retained ordered secondary structure and comigrated with the wild-type proteins in non-denaturing gel electrophoresis. The loss of the protein binding can be ascribed to introduction of a nick because a mutant protein that had Met in place of Leu157 but no nick was able to specifically bind to the functional site of PSII complexes and restore the oxygen-evolving activity as effectively as the wild-type protein. In contrast, a mutant MSP with Met inserted between Phe156 and Leu157 bound only weakly and non-specifically to PSII complexes and failed to reactivate oxygen evolution. Thus, the binding of the protein to the functional site of the PSII complex was highly sensitive to a small structural change that was caused by cleavage or insertion of a single amino acid residue between Phe156 and Leu157. The results suggest that the Phe156-Gly163 and Arg184-Ser191 sequences of the cyanobacterial MSP are regions for interaction with PSII complexes.

Amino Acid Sequence↗
PubMed1998

Identification of Xenopus SMC protein complexes required for sister chromatid cohesion.

The structural maintenance of chromosomes (SMC) family is a growing family of chromosomal ATPases. The founding class of SMC protein complexes, condensins, plays a central role in mitotic chromosome condensation. We report here a new class of SMC protein complexes containing XSMC1 and XSMC3, Xenopus homologs of yeast Smc1p and Smc3p, respectively. The protein complexes (termed cohesins) exist as two major forms with sedimentation coefficients of 9S and 14S. 9S cohesin is a heterodimer of XSMC1 and XSMC3, whereas 14S cohesin contains three additional subunits. One of them has been identified as a Xenopus homolog of the Schizosaccharomyces pombe Rad21p implicated in DNA repair and the Saccharomyces cerevisiae Scc1p/Mcd1p implicated in sister chromatid cohesion. 14S cohesin binds to interphase chromatin independently of DNA replication and dissociates from it at the onset of mitosis. Immunodepletion of cohesins during interphase causes defects in sister chromatid cohesion in subsequent mitosis, whereas condensation is unaffected. These results suggest that proper assembly of mitotic chromosomes is regulated by two distinct classes of SMC protein complexes, cohesins and condensins.

Adenosine Triphosphatases↗
PubMed1998

Distribution of functional glutamate receptors in cultured embryonic Drosophila myotubes revealed using focal release of L-glutamate from caged compound by laser.

During the formation of neuromuscular junctions in Drosophila embryos, glutamate receptors undergo a drastic change in distribution. To study the underlying mechanism of this developmental process, it is desirable to map the distribution of functional receptors with accurate spatial resolution. Since glutamate receptors desensitize within several milliseconds, the agonist must be applied rapidly. To fulfil these requirements we used laser stimulation of a caged compound to release L-glutamate at a focal spot. Since the glutamate receptor channel is permeable to Ca2+, we assayed the change in internal Ca2+ concentration using a Ca2+ indicator, fluo-3. Using this approach, we mapped the distribution of functional glutamate receptors in cultured embryonic Drosophila myotubes and myoblasts. Consistent with previous immunofluorescence studies using an antibody against a glutamate receptor subunit, a large increase of internal Ca2+ concentration was observed when laser stimulation was located close to some nuclei in the myotube. No change was detected when the laser stimulus was applied over any regions of the myoblasts. No increase of the internal Ca2+ concentration in myotubes was observed when the external solution contained either glutamate at a desensitizing concentration (1 mM) or a glutamate receptor channel blocker, argiotoxin (1 microg/ml). These results indicate that a rise in intracellular Ca2+ concentration can be used to show the distribution of the functional receptor on the muscle surface membrane.

Animals↗