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Biomedical subjects

K Omori

Publications and source records attributed to K Omori.

At least 73 records · Page 4Linked to original sources

Long-lasting c-fos and NGF mRNA expressions and loss of perikaryal parvalbumin immunoreactivity in the development of epileptogenesis after ethacrynic acid-induced seizure.

A single cerebroventricular injection of ethacrynic acid (EA), a Cl(-)-ATPase inhibitor, induces generalized tonic-clonic convulsions in mice. To clarify whether such convulsive stimulus triggers a long-lasting rearrangement of the neural circuitry culminating in seizure susceptibility, we examined molecular, cellular and behavioral changes following the EA-induced seizure. The expression of immediate early gene c-fos mRNA as an index for cellular activation increased biphasically, with an early transient increase at 60 min and a late prolonged increase on the 10th to 14th day post-EA administration, most remarkably in the hippocampus and pyriform cortex. On the 14th day post-EA seizure, subconvulsive dose of kainic acid (5-17.5 mg/kg) caused severe (stage 5) seizure in 77% of the mice, with 70% mortality. In addition, the expression of nerve growth factor (NGF) also showed biphasic increases with close spatiotemporal correlation with c-fos expression. Moreover, the number of cell somata and the density of axon fibers of parvalbumin (PARV)-positive cells, a subpopulation of GABAergic interneurons, decreased in area dentata, CA1 and CA3 on the 7th and 14th day post-EA seizure. In area dentata and CA1, the density of glutamic acid decarboxylase (GAD)-positive cells also decreased on the 14th day. Thus, the transient EA-induced seizures appear to develop seizure susceptibility by causing damage of a subpopulation of inhibitory interneurons along with increases in the expression of c-fos and NGF in limbic structures.

Animals↗

Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A).

cDNA encoding a novel phosphodiesterase (PDE) was isolated from a human fetal lung cDNA library and designated PDE10A. The deduced amino acid sequence contains 779 amino acids, including a putative cGMP binding sequence in the amino-terminal portion of the molecule and a catalytic domain that is 16-47% identical in amino acid sequence to those of other PDE families. Recombinant PDE10A transfected and expressed in COS-7 cells hydrolyzed cAMP and cGMP with Km values of 0.26 and 7.2 microM, respectively, and Vmax with cGMP was almost twice that with cAMP. Of the PDE inhibitors tested, dipyridamole was most effective, with IC50 values of 1.2 and 0.45 microM for inhibition of cAMP and cGMP hydrolysis, respectively. cGMP inhibited hydrolysis of cAMP, and cAMP inhibited cGMP hydrolysis with IC50 values of 14 and 0.39 microM, respectively. Thus, PDE10A exhibited properties of a cAMP PDE and a cAMP-inhibited cGMP PDE. PDE10A transcripts were particularly abundant in the putamen and caudate nucleus regions of brain and in thyroid and testis, and in much lower amounts in other tissues. The PDE10A gene was located on chromosome 6q26 by fluorescent in situ hybridization analysis. PDE10A represents a new member of the PDE superfamily, exhibiting unique kinetic properties and inhibitor sensitivity.

Amino Acid Sequence↗

Lithium decreases Cl--ATPase activity and increases intracellular Cl- concentration in cultured rat hippocampal neurons.

Under the conditions of stimulated phosphatidylinositol turnover (0. 1 mM carbachol plus 20 mM KCl), LiCl (0.1-10 mM) reduced the activity of Cl--ATPase in cultured rat hippocampal neurons without affecting Na+/K+- or anion-insensitive Mg2+-ATPase. This inhibition of Cl--ATPase was attenuated by the addition of 0.5 mM inositol to culture media. The intracellular Cl- concentrations of the LiCl-treated neurons increased in an inositol-sensitive manner.

Adenosine Triphosphatases↗

Vibratory analysis of the neoglottis after surgical intervention of cricopharyngeal myotomy and implantation of tracheal cartilage.

OBJECTIVE: To examine the effect of a new surgical intervention, consisting of cricopharyngeal myotomy and tracheal cartilaginous implantation on the anterior wall of the esophagus, for tracheoesophageal shunt and esophageal phonation. DESIGN: We examined the vibration of the neoglottis of tracheoesophageal shunt and esophageal speakers after total laryngectomy using a high-speed video camera (frame rate, 1000 per second). PATIENTS: Twenty-one alaryngeal patients were involved: 13 who had undergone the present procedure and 8 who had not. RESULTS: The regularity of neoglottal vibration and the degree of neoglottal closure were significantly (P<.01) better in patients who had undergone the procedure than in those who had not. These effects on neoglottal vibration induced easier phonation. CONCLUSIONS: Cricopharyngeal myotomy was useful for avoiding reconstructed esophageal spasm, and tracheal cartilaginous implantation was effective for maintaining a wide subneoglottal space. This combination of procedures is useful for obtaining optimal vibration of the neoglottis in tracheoesophageal shunt and esophageal speakers.

Aged↗

Analysis of Rotational Transitions in Excited Vibrational States of Propionitrile (C2H5CN).

We have observed rotational transitions of propionitrile (C2H5CN) in the 8-200 GHz region and assigned 208 transitions with J </= 16 and Ka </= 2 in the first excited state of torsional vibration, 244 transitions with J </= 16 and Ka </= 2 in the first excited state of CCN in-plane bending vibration, and 374 transitions with J </= 16 and Ka </= 4 in the first excited state of CCN out-of-plane bending vibration. We simultaneously analyzed these transitions in the three excited vibrational states, combining with the previously reported transitions in the ground vibrational state, on the basis of a Hamiltonian including CCN-bending vibration-torsion-rotation interactions. A total of 1560 transitions were fitted with 0.95-MHz 1varsigma standard deviation, and molecular constants were determined. Copyright 1999 Academic Press.

Journal Article↗

Neoglottic vibration in tracheoesophageal shunt phonation.

The purpose of the present study was to examine vibratory patterns of the neoglottis and to ascertain the neoglottic conditions that could cause failure in tracheoesophageal shunt phonation. We studied 30 tracheoesophageal shunt speakers while using "trap-door" type voice prostheses. Videostroboscopy was undertaken to investigate vibratory patterns of the neoglottis during phonation of the sustained vowel sound /e/ in these patients. The voice qualities of the patients were judged perceptually. A regular neoglottic vibration was observed in 21 patients. Nine patients had irregular neoglottic vibrations. In this latter group, two patients had incomplete neoglottic closures with breathy voices, four patients had multiple contacts of several mucosal walls with rough voices, and three patients had tight neoglottic closures with strained voices. During stroboscopic evaluation of tracheoesophageal shunt phonation, regularity of the neoglottic vibration may be the most significant finding. These findings show that it is as important to evaluate neoglottic vibration in alaryngeal voicing as it is to study glottic vibration in laryngeal voicing. Stroboscopic examination may be a help to elucidate a cause of failure in cases of poor tracheoesophageal shunt speech.

Aged↗

Surgical rescue for life-threatening hypoxemia caused by a mediastinal tumor.

We recently encountered a patient with a large anterior mediastinal tumor who developed severe hypoxemia during general anesthesia. This life-threatening hypoxemia was treated by extracorporeal membrane oxygenation using emergent percutaneous cardiopulmonary support followed by extirpation of the tumor. We found that total arteriovenous shunt resulting from compression by the mediastinal tumor caused this severe hypoxemia (total obstruction of left main bronchus and of the right pulmonary artery).

Adult↗

Clinical spectrum of congenital cystic disease of the lung in children.

OBJECTIVES: Congenital cystic lesions of the lung are uncommon but share similar embryologic and clinical characteristics. The purpose of this study is to review our institutional experience of congenital cystic lung disease, emphasizing the clinical spectrum of the disease related to age, and present some cases with unusual clinical manifestations. PATIENTS: Between 1962 and 1996, 26 patients (9 females and 17 males) under 15 years old underwent evaluation and surgical treatment for congenital cystic lung disease. Seven patients were under 1 year old, and 19 were in over 1 year old. There were 13 bronchogenic pulmonary cysts, 6 pulmonary sequestrations, 4 congenital cystic adenomatoid malformations (CCAM), and 3 congenital lobar emphysemas. RESULTS: All patients under 1 year old showed respiratory distress with mediastinal shift but no episodes of infection. In contrast, 13 of the 19 patients over 1 year old had symptoms of recurrent infection without respiratory distress. Five patients over 1 year old were entirely asymtomatic from birth. There were significant differences (P < 0.05) in the frequencies of respiratory distress and infection between the two groups (chi2-test). Lobectomy was performed in 21 patients, excision in 3 patients, segmentectomy in one patient, and exploration in one patient. There was no incident of postoperative mortality or morbidity except for one patient with CCAM complicated by reexpansion lung edema. Twenty-one patients at long-term follow-up from 2 to 30 years after surgery are doing well with no subsequent limitation of physical activities due to lung resection. CONCLUSIONS: In patients under 1 year old, cystic lesions were discovered by respiratory distress; and in patients over 1 year old signs of infection were the most important clinical features. Early recognition of these relatively rare congenital cystic lung lesions would lead to the immediate, proper surgical intervention.

Adolescent↗

Long-term treatment with antidepressants increases glucocorticoid receptor binding and gene expression in cultured rat hippocampal neurones.

Since the glucocorticoid receptor (GR) and/or mineralocorticoid receptor (MR) in the hippocampus have been implicated in cortisol feedback of the hypothalamus-pituitary-adrenal (HPA) axis, abnormalities in those receptors might underlie the hyperactivity of the HPA axis described in patients with major depression. Animal studies have shown that long-term in-vivo treatment with antidepressants up-regulates hippocampal GR and/or MR, but it is not clear whether this up-regulation is evoked through a direct action of antidepressants on these receptors. We therefore examined the direct effects of long-term antidepressant treatment on GR binding and the levels of GR messenger RNA (mRNA) in primary cultures of rat hippocampal neurones. The time course of the effects of the tricyclic antidepressants desipramine and amitriptyline on GR binding, as assessed by [3H]dexamethasone binding using RU 28362, a specific agonist for GR, showed a biphasic mode of stimulation: desipramine significantly increased the GR binding with 2-day exposure by 36% over that in controls and by 99% and 60% with 10- and 14-day exposures, respectively. Amitriptyline also led to a significant increase in GR binding, with peaks at 2 (by 60%) and 14 days of exposure (by 60%). The effects of 14-day treatment with desipramine required at least the first 4-day exposure, and the first 10-day exposure was required for the full effect. Northern blot analysis demonstrated that the GR mRNA level was significantly increased by 14-day treatment with desipramine (+142% over control), amitriptyline (+108%), mianserin (+124%), paroxetine (+42%) and sulpiride (+92%), but not with haloperidol. Immunocytochemistry for GR revealed that 2- or 14-day treatment with desipramine significantly increased the number of GR-positive cells with dominant immunoreactivity in the nuclei of granule cell-like neurones or in perikarya of pyramidal cell- and granule cell-like neurones. These findings suggest that tricyclic antidepressants directly increase hippocampal GR by short-term (2-day) and long-term (14-day) exposure, and that the increase by long-term exposure is evoked commonly with different classes of antidepressants through transcriptional up-regulation of GR expression.

Amitriptyline↗

Genomic origin and transcriptional regulation of two variants of cGMP-binding cGMP-specific phosphodiesterases.

We have reported alternative splice variants of cGMP-binding cGMP-specific phosphodiesterases (PDE5A), i.e. rat PDE5A2, human PDE5A1, canine PDE5A1 and PDE5A2, which possess distinct N-terminal sequences. In this study, the DNA sequences corresponding to the unique N-terminal portions of PDE5A1 and PDE5A2 were shown to be tandemly located upstream of exons encoding the common region of PDE5A in both human and rat PDE5A genes. The presence of human PDE5A2 and rat PDE5A1 transcripts in lung was confirmed by reverse transcriptase-PCR. These results indicated that two variant forms of PDE5A exist in humans, canines and rats. We examined the tissue distribution of the two variants of human PDE5A in adult and fetal humans. The patterns of expression of the two alternatively spliced transcripts of human PDE5A in human tissues differed. Many putative regulatory elements including cAMP response elements were observed in the 5'-untranslated region and intron of the PDE5A gene. The levels of the PDE5A transcripts, especially the PDE5A2 transcripts, were increased by a cAMP analogue in cultured rat vascular smooth muscle cells, indicating that the PDE5A2 is an inducible variant of PDE5A in rats.

3',5'-Cyclic-GMP Phosphodiesterases↗

Striatum- and testis-specific phosphodiesterase PDE10A isolation and characterization of a rat PDE10A.

PDE10A, a phosphodiesterase (PDE) exhibiting properties of a cAMP PDE and a cAMP-inhibited cGMP PDE, was cloned and investigated in detail in rats. PDE10A transcripts were abundant in the brain and testis. In situ hybridization analysis using a PDE10A riboprobe demonstrated the presence of PDE10A transcripts in the neurons of the striatum and the olfactory tubercle regions of the brain. Rat PDE10A cDNAs were isolated from a brain cDNA library and nucleotide sequence analysis revealed several N-terminal variants. The deduced amino-acid sequence of one of the major variant forms contained 794 amino acids, and it was 96% identical to that of the human PDE10A2. The other major form has a distinct N-terminal sequence that is not found in humans. PDE10A was partially purified from rat striatum and testis, and characterized with respect to Km, inhibitor sensitivity and immunoreactivity to an anti-PDE10A serum. These findings indicate that PDE10A functions in these tissues.

Alternative Splicing↗

Cloning and characterization of the Pseudomonas fluorescens ATP-binding cassette exporter, HasDEF, for the heme acquisition protein HasA.

Two ATP-binding cassette (ABC) exporters are present in Pseudomonas fluorescens no. 33; one is the recently reported AprDEF system and the other is HasDEF, which exports a heme acquisition protein, HasA. The hasDEF genes were cloned by DNA hybridization with a DNA probe coding for the LipB protein, one of the components of the Serratia marcescens ABC exporter Lip system. P. fluorescens HasA showed sequence identity of 40 to 49% with HasA proteins from Pseudomonas aeruginosa and Serratia marcescens. The P. fluorescens Has exporter secreted HasA proteins from P. fluorescens and P. aeruginosa but not S. marcescens HasA in Escherichia coli, whereas the Has exporter from S. marcescens allowed secretion of all three HasA proteins. The P. fluorescens HasDEF system also promoted the secretion of the lipase and alkaline protease of P. fluorescens. Hybrid exporter analysis demonstrated that the HasD proteins, which are ABC proteins, are involved in the discrimination of export substrates. Chimeric HasA proteins containing both P. fluorescens and S. marcescens sequences were produced and tested for secretion through the Has exporters. The C-terminal region of HasA was shown to be involved in the secretion specificity of the P. fluorescens Has exporter.

ATP-Binding Cassette Transporters↗

A 60 kDa plasma membrane protein changes its localization to autophagosome and autolysosome membranes during induction of autophagy in rat hepatoma cell line, H-4-II-E cells.

We previously reported the preparation and characterization of an antibody against membrane fraction of autolysosomes from rat liver (J. Histochem. Cytochem. 38, 1571-1581, 1990). Immunoblot analyses of total membrane fraction of a rat hepatoma cell line, H-4-II-E cells by this antibody suggested that H-4-II-E cells expressed several autolysosomal proteins, including a protein with apparent molecular weight of 60 kDa. It was suggested that this 60 kDa protein was a peripheral membrane protein, because it was eluted from the membrane by sodium carbonate treatment. We prepared an antibody against this 60 kDa protein by affinity purification method, and examined its behavior during induction of autophagy. Autophagy was induced by transferring the cells from Dulbecco's modified Eagle medium (DMEM) containing 12% fetal calf serum into Hanks' balance salt solution. In DMEM, the 60 kDa protein showed diffused immunofluorescence pattern, and immunoelectron microscopy suggested that this protein was located on the extracellular side of the plasma membrane. After inducing autophagy, the immunofluorescence configuration of the 60 kDa protein changed from the diffused pattern to a granulous one. Immunoelectron microscopy showed that the 60 kDa protein was localized on the luminal side of the limiting membrane of autolysosomes and endosomes. In the presence of bafilomycin A1 which prevents fusion between autophagosomes and lysosomes, the 60 kDa protein was localized on the limiting membrane of the autophagosomes and endosomes. These results suggest that the 60 kDa protein is transported from the plasma membrane to the autophagosome membrane through the endosomes.

Animals↗

[Molecular mechanism underlying epileptic seizure: forwards development of novel drugs for untreatable epilepsy].

For the development of new drugs for hitherto untreatable epilepsy, it is necessary to clarify the basic pathophysiology involved in such epileptic seizures and find the target site. This review focused on molecular events related to the expression and expansion of the epileptic focus which are the target of novel antiepileptics. Immediate early genes such as c-fos followed by expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been evidenced as initial important phenomena in the cascade of molecular systems that develop and complement the transient neuronal excitation to long-term neuronal plasticity. Non-receptor type tyrosine kinase Fyn in the Src family has been suggested to promote kindling development via tyrosine phosphorylation of the NMDA-receptor subunit, NR2B. The cause of abnormality in the inhibitory system is induced by lowering of glutamate-dependent GABA release in the epileptic focus within the hippocampus in human temporal epilepsy. This is probably attributed to a decrease in GABA transporters. Regarding abnormality of the excitatory system, there is an increase in glutamate release prior to convulsive seizures, an enhancement of NMDA receptor responsiveness and high levels of AMPA receptors related to convulsion after completion of kindling. In gene analysis of human familiar epilepsy, abnormalities and point mutations have recently been found in the following genes: KCNQ 2 and KCNQ3, coding for K+ channels; CHRNA4 of the nicotinic receptor subunit alpha 4; and the cystatin B gene. In epilepsy model mice, EL mice with several gene mutations known to be involved in the seizures, the El-1 gene contains an abnormality of the ceruloplasmin gene. SER (spontaneously epileptic rat: zi/zi, tm/tm), a double mutant, manifests a deletion of the region containing the aspartoacylase gene related to the tm gene. Since an increase in N-acetyl-L-aspartate (NAA) is observed in the SER brain, NAA may serve to evoke seizures.

Amidohydrolases↗

Natriuretic peptide receptors, NPR-A and NPR-B, in cultured rabbit retinal pigment epithelium cells.

We tried to detect natriuretic peptide (NP) receptor (NPR-A and NPR-B) mRNAs in cultured rabbit retinal pigment epithelium (RPE) cells and examined the regulation of their expression in relation to subretinal fluid absorption or RPE cell proliferation. RPE cells from 2-4 passages were grown to confluence on microporous membranes and analyzed for levels of expression of receptor mRNAs by quantitative RT-PCR and Northern blotting. The expression of NPR-B mRNA was approximately tenfold higher than that of NPR-A mRNA. The expression of NPR-A mRNA was not affected by treatments that may change subretinal fluid transport, while that of NPR-B mRNA was inhibited by transmitters involved in light- and dark-adaptation such as dopamine and melatonin. Expression of NPR-B mRNA was also suppressed by platelet-derived growth factor and transforming growth factor-beta. Furthermore, atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP), ligands for NPR-A and B, respectively, inhibited the proliferation of RPE cells, as analyzed by incorporation of [3H]thymidine. These findings suggest that ANP may be involved in constitutive absorption of subretinal fluid and that NPs form an important regulatory system of proliferation in RPE cells.

Acetazolamide↗

Adrenocorticotropic hormone-independent bilateral adrenocortical macronodular hyperplasia treated with mitotane.

We report a case of adrenocorticotropic hormone (ACTH)-independent bilateral macronodular adrenocortical hyperplasia (AIMAH), which was successfully treated with mitotane. A 71-year-old man visited our hospital because of central obesity and enlarged bilateral adrenal glands. The endocrinological studies showed elevated plasma cortisol and undetectable levels of ACTH, a lack of suppression with high-dose dexamethasone and a hyper-response to exogenous ACTH. These clinical features were compatible with the diagnosis of AIMAH. In this patient, extra-adrenal multiple tumors were also detected. After treatment with mitotane, the plasma level of cortisol was decreased while that of ACTH was increased and the signs of Cushing's syndrome were resolved.

Adrenal Cortex↗

Effects of thermal cycling on dynamic viscoelastic properties of four commercial resins for crown and bridge.

To elucidate the effects of thermal cycling on the viscoelastic properties of four commercial resins for crown and bridge, dynamic shear modulus (G'), mechanical loss tangent (tan delta), Knoop hardness, water sorption and appearance of specimen surfaces before and after thermal cycling test were determined. The changes of G' and tan delta for two materials were insignificant with increased repetitions of thermal cycling. Those of the other two materials were statistically significant: in particular, G' at temperatures above 60 degrees C was inclined to increase slightly and tan delta decreased considerably. While the Knoop hardness of the materials was a little decreased over a number of 75,000 thermal cycles, the water sorption almost attained an equilibrium in uptake after 14,000 thermal cycles. Furthermore, cracks on the specimen surface were observed after 37,500 to 75,000 thermal cycles. From these results, the deterioration of materials was observed as damage to the specimen surface. Moreover, it could be presumed that the materials would be further polymerized during the period of thermal cycling.

Analysis of Variance↗