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K Ohta

Publications and source records attributed to K Ohta.

At least 199 records · Page 11Linked to original sources
PubMed1999

Synthesis and SAR of 1-alkyl-2-phenylethylamine derivatives designed from N,N-dipropyl-4-methoxy-3-(2-phenylethoxy)phenylethylamine to discover sigma(1) ligands.

The synthesis and structure-activity relationships (SAR) of 1-alkyl-2-phenylethylamine derivatives 5-8 designed from N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine hydrochloride (1, NE-100) are presented. The SAR between compound 1 and 1-alkyl-2-phenylethylamine derivatives suggested that the alkyl group on the 1-position carbon of 2-[4-methoxy-3-(2-phenylethyl)phenyl]ethylamine derivatives played the role of one of the propyl groups on the aminic nitrogen of compound 1. (-)-N-Propyl-1-butyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylam ine hydrochloride ((-)-6d, NE-537) and (-)-N-propyl-1-(3-methybutyl)-2-[4-methoxy-3-(2-phenylethoxy )phenyl]e thylamine hydrochloride ((-)-6i, NE-535), typical compounds in this series, have potent and selective sigma(1) affinity.

Alkylation↗
PubMed1999

Simultaneous determination of anions and cations by ion-exclusion chromatography-cation-exchange chromatography with tartaric acid/18-crown-6 as eluent.

Ion-exclusion chromatography-cation-exchange chromatography was developed for the simultaneous separation of common inorganic anions and cations (Cl-, NO3- and SO4(2-); Na+, NH4+, K+, Mg2+ and Ca2+) on a weakly acidic cation-exchange column by elution with weak acid. Generally, the resolution among these monovalent cations was only moderate, thereby hindering the determination of these analytes in natural-water samples. Therefore, 18-crown-6 was added to the eluent to improve the resolution. A good separation of these anions and cations on a weakly acidic cation-exchange column was achieved in 30 min by elution with 5 mM tartaric acid/6 mM 18-crown-6/methanol-water (7.5:92.5). The ion-exclusion chromatography-cation-exchange chromatography method developed here was successfully applied to the separation of major anions and cations in an environmental water sample.

Anions↗
PubMed1999

Ion-exclusion chromatography of carboxylic acids on silica gel modified with aluminium.

The modification of silica gel with aluminium by a coating method was effective for the preparation of a silica-based stationary phase, which acted as a cation exchanger under strongly acidic conditions. In order to expand the utility of the laboratory-made aluminium-adsorbing silica gel it was applied as a stationary phase to the ion-exclusion chromatography of various carboxylic acids. Good separations for both aliphatic carboxylic acids and benzenecarboxylic acids with a hydrophobic nature under acidic eluent conditions were achieved in 25 min.

Aluminum↗
PubMed1999

Acid-rain monitoring in east Asia with a portable-type ion-exclusion-cation-exchange chromatographic analyzer.

A monitoring system consisting of a portable-type conductimetric ion-exclusion-cation-exchange chromatographic (CEC) analyzer and a meteorological satellite data analyzer has been investigated for the evaluation of the effects of acid precipitation on natural and urban environments in East Asia. The portable ion-exclusion-CEC analyzer uses a polymethacrylate-based weakly acidic cation-exchange resin column in the H(+)-form and a weak-acid eluent (tartaric acid-methanol-water) and is applied for the simultaneous determination of anions (SO4(2)-, NO3-, and Cl-) and cations (Na+, NH4+, K+, Mg2+, and Ca2+) in precipitation transported from mainland China to central Japan, as mapped by the meteorological satellite data analyzer. Linear calibration graphs of peak area versus concentration for anions and cations were observed in the concentration range 0-1.0 mM for the anions and 0-0.5 mM for the cations. Detection limits at a signal-to-noise ratio of 3 were in the range 5.18-12.1 ppb for the anions and 6.58-16.5 ppb for the cations. The practical utility of this monitoring system is presented.

Acid Rain↗
PubMed1999

Simultaneous separation of common mono- and divalent cations on silica gel modified with aluminium by non-suppressed ion chromatography with conductimetric detection and nitric acid-15-crown-5 as eluent.

The modification of silica gel with aluminium by a coating method was very effective for the preparation of silica-based stationary phases which acted as a cation exchanger under strongly acidic conditions. However, the separation of common mono- and divalent cations (Li+, Na+, NH4+, K+, Mg2+ and Ca2+) on an aluminium-adsorbing silica (Al-Silica) column was moderate by a conductimetric detection ion chromatography (IC) with strongly acidic eluents. Then, the addition of various crown ethers (12-crown-4, 15-crown-5 and 18-crown-6) in acidic eluent was carried out. As a result, it was found that 15-crown-5 was most effective for the improvement of peak resolution. Excellent separation of these cations was achieved in 20 min by elution with 2 mM nitric acid-2 mM 15-crown-5. The proposed IC was successfully applied to the determination of major cations in various natural waters.

Aluminum↗
PubMed1999

Embryonic lens repels retinal ganglion cell axons.

During development of the vertebrate visual system, retinal ganglion cell (RGC) axons follow a precise path toward their midbrain targets. Although much is known about the cues that direct RGC axons once they have left the optic disc, less is known about the guidance of axons at earlier stages, when RGCs first send out their axons to navigate within the developing retina. Using collagen gel coculture experiments, we find that the embryonic lens produces a powerful diffusible repulsive activity for RGC axons. We also find that this activity is localized to the lens epithelium and not the lens fiber layer, while the pigmented epithelium and vitreous humour are devoid of activity. The further observation that the lens also chemorepels primary sensory axons, but does not repel olfactory bulb axons, shows that this activity is specific for subsets of axons. Our experiments have excluded two candidate repellents for RGC axons (collapsin-1/sema III and chondroitin sulfate proteoglycans). These results implicate the lens in the earliest stages of RGC axon guidance. One function of the lens repellent may be to prevent aberrant targeting toward the lens, and it may also be involved in the directional guidance of RGC axons toward the optic disc.

Animals↗
PubMed1999

Isolation and characterization of low density detergent-insoluble membrane (LD-DIM) fraction from sea urchin sperm.

The low density detergent-insoluble membrane (LD-DIM) fraction was obtained by a sucrose-density gradient centrifugation from sperm of three sea urchin species, Hemicentrotus pulcherrimus, Strongylocentrotus purpuratus, and Anthocidaris crassispina. These LD-DIM preparations were characterized by enriched glycosphingolipids (GSL) including gangliosides and sulfatide (SLF), having more than 50% of the total amount of GSL present in these sperm. Interestingly, a minor component of H. pulcherrimus sperm (HO3S-->8Neu5Acalpha2-->8Neu5Acalpha2-->6Glcbeta1++ +-->Cer) was shown to be even more enriched in the LD-DIM as revealed by using monoclonal antibody (mAb.3G9) speific to this ganglioside. In addition to the GSL, phosphatidyl-serine (PS) and diacylglcerol (DG) were enriched in the LD-DIM. On the other hand, cholesterol (CL) and sphingomyelin (SM) were not so enriched, which contrasted with the LD-DIM from Madin-Darby canine kidney (MDCK) cells, where CL and SM were reported to be abundant. Because mammalian somatic cell-derived DIMs have been proposed to be associated with functional signal transduction, it seems possible that the ganglioside-enriched LD-DIM in sea urchin sperm can participate in binding to eggs and the subsequent egg activation process. To our knowledge this is the chemical characterization of the LD-DIM fraction of a gametic cell.

Animals↗
PubMed1999

Competitive inactivation of a double-strand DNA break site involves parallel suppression of meiosis-induced changes in chromatin configuration.

In Saccharomyces cerevisiae, DNA double-strand breaks (DSBs) initiate meiotic recombination at open sites in chromatin, which display a meiosis-specific increase in micrococcal nuclease (MNase) sensitivity. The arg4 promoter contains such a DSB site. When arg4 sequences are placed in a pBR322-derived insert at HIS4 (his4 :: arg4 ), the presence of strong DSB sites in pBR322 sequences leads to an almost complete loss of breaks from the insert-borne arg4 promoter region. Most of the MNase-sensitive sites occurred at similar positions in insert-borne and in normal ARG4 sequences, indicating that hotspot inactivation is not a consequence of changes in nucleosome positioning. However, a meiosis-specific increase in MNase hypersensitivity was no longer detected at the inactive insert-borne arg4 DSB site. Elimination of pBR322 sequences restored DSBs to the insert-borne arg4 promoter region and also restored the meiotic induction of MNase hypersensitivity. Thus, the meiotic induction of MNase hypersensitivity at the DSB sites is suppressed and activated in parallel to DSBs themselves, without changes in the underlying DNA sequence or nucleosome positioning. We suggest that meiosis-specific changes in chromatin at a DSB site are a signal reflecting a pivotal step in DSB formation.

Argininosuccinate Lyase↗
PubMed1999

A DNA unwinding factor involved in DNA replication in cell-free extracts of Xenopus eggs.

BACKGROUND: Alteration of chromatin structure is a key step in various aspects of DNA metabolism. DNA unwinding factors such as the high mobility group (HMG) proteins are thought to play a general role in controlling chromatin structure and a specific role in controlling DNA replication. For instance, in the in vitro simian virus 40 replication system, minichromosomes containing HMG-17 replicate more efficiently than those without it, suggesting that HMG-17 enhances the rate of replication of a chromatin template by unfolding the higher-order chromatin structure. At present, however, only limited data suggest an involvement of DNA unwinding factors in DNA replication. RESULTS: We purified from Xenopus eggs a novel heterodimeric factor, termed DNA unwinding factor (DUF), that consists of 87 kDa and 140 kDa polypeptides. DUF unwinds closed-circular duplex DNA in the presence of topoisomerase I, but it does not possess a DNA gyrase activity: it does not introduce negative supercoils into DNA at the expense of ATP hydrolysis. Cloning and sequencing of the cDNAs encoding the two polypeptides revealed that the 87 kDa polypeptide is homologous to a mammalian HMG protein, T160/structure-specific recognition protein. The 140 kDa polypeptide is homologous to yeast Cdc68, a protein that controls the expression of several genes during the G1 phase of the cell cycle by modulating chromatin structure. Immunodepletion of DUF from Xenopus egg extracts drastically reduced the ability of the extract to replicate exogenously added sperm chromatin or plasmid DNA. CONCLUSIONS: We propose that DUF plays a role in DNA replication in Xenopus egg extracts.

Amino Acid Sequence↗
PubMed1999

Design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine sigma ligands as potential antipsychotic drugs.

sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2 receptor. This compound was designed to eliminate two bonds of apomorphine 1 to produce structural flexibility for the nitrogen atom and to bridge two benzene rings with a -CH2O- bond to maintain the planar structure. In light of the evidence, N, N-dipropyl-2-(4-methoxy-3-benzyloxylphenyl)ethylamine hydrochloride 10b was designed. Since compound 10b had eliminated a biphenyl bond of 6H-dibenzo[b,d]pyran derivative 2a, it might be more released from the rigid structure of apomorphine 1 than compound 2a. The chemical modification of compound 10b led to the discovery that N, N-dipropyl-2- [4-methoxy-3-(2-phenylethoxyl)phenyl]ethylamine hydrochloride 10g (NE- 100), the best compound among arylalkoxyphenylalkylamine derivatives 3, had a high and selective affinity for sigma receptor and had a potent activity in an animal model when the drug was given orally. We report here the design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine derivatives 3.

Animals↗
PubMed1999

Bone-peg grafting for osteochondritis dissecans of the elbow.

In the treatment of osteochondritis dissecans involving the elbow, we have used a bone-peg graft taken from the proximal part of the ulna and inserted into the defect. Thirty-two patients were followed from 2 to 10.5 years. The graft was utilised in 20 elbows, and 6 of these also had concomitant removal of a loose body. Another 6 elbows had removal of a loose body only. Ten elbows were treated conservatively in 5 of these the outcome was unsatisfactory, including 4 in which a bone-peg graft was later necessary. The bone-peg graft gave the best short-term results. Bony union of the dissecans site and reconstitution of subchondral bone required an average of 6.5 months. In 15 patients followed for a minimum of 5 years, the bone-peg graft was effective in limiting the development of osteoarthritis. Bone-peg grafting is a reliable method for treating osteochondritis dissecans of the elbow.

Adolescent↗
PubMed1999

Malignant rhabdoid tumor of the colon: report of a case.

A malignant rhabdoid tumor of the colon is very rare and only three cases have been previously described. A 76-year-old man was admitted to the hospital complaining of epigastralgia. An elastic mass was palpable in the right upper abdomen. A barium enema and endoscopic examination showed a giant gyrate tumor arising from the cecum. Abdominal ultrasonography and a computed tomography scan revealed the tumor to be located in the colon associated with multiple liver metastases and gallbladder stones. A right colectomy and cholecystectomy were thus performed. The tumor was histologically composed of sheets of large round and polygonal nuclei with vesicular chromatin, and abundant acidophilic cytoplasm, often containing hyalin-like inclusion. The cytoplasm was positive for vimentin and neuron-specific enolase, and hyaline globules of the rhabdoid tumor cells stained positive for cytokeratin in some cells. Transmission electron microscopy showed characteristic rhabdoid cells with an aggregation of intermediate filaments. A histologic diagnosis of malignant rhabdoid tumor of the colon was made. The tumor demonstrated several unusual findings for malignant rhabdoid tumors including diploidy by a flow cytometric analysis, and positive nuclear immunohistochemical staining for p53 protein and Ki-67 antigen. We report herein the third known case of a pure colonic rhabdoid tumor.

Aged↗
PubMed1999

Diesel exhaust particulate induces airway hyperresponsiveness in a murine model: essential role of GM-CSF.

BACKGROUND: Inhaled pollutants were recently shown to be responsible for an increased incidence of airway allergic diseases, including asthma. A common feature of all forms of asthma is airway hyperresponsiveness. OBJECTIVE: Our purpose was to elucidate the effects of diesel exhaust particulate (DEP), one of the most prevalent inhaled pollutants, on airway responsiveness. METHODS: A/J and C57Bl/6 mice were used; the former are genetically predisposed to be hyperresponsive to acetylcholine, whereas the latter are not. DEP was administered intranasally for 2 weeks, after which pulmonary function was analyzed by whole-body plethysmography. RESULTS: Intranasal administration of DEP increased airway responsiveness to acetylcholine in both A/J and C57Bl/6 mice and induced displacement of ciliated epithelial cells by mucus-secreting Clara cells. The effect was mediated by M(3) muscarinic receptors. Acetylcholine-evoked bronchial constriction was reversed by administration of terbutaline, a beta(2)-adrenergic antagonist, which is also characteristic of human asthma. Intranasal administration of antibody raised against GM-CSF abolished DEP-evoked increases in airway responsiveness and Clara cell hyperplasia. The antibody raised against IL-4 also inhibited DEP-evoked increases in airway responsiveness. However, it was to a lesser extent compared with antibody against GM-CSF. In addition, DEP stimulated GM-CSF messenger RNA expression in the lung. CONCLUSION: DEP induces airway hyperresponsiveness by stimulating GM-CSF synthesis.

Acetylcholine↗
PubMed1999

Apoptosis of eosinophils and lymphocytes in allergic inflammation.

A characteristic feature of apoptosis is that the cellular contents that are biologically active are always surrounded by the cell membrane throughout the entire process. Thus the apoptotic cells are eliminated calmly and quickly without evoking inflammation. In allergic inflammation activated eosinophils and lymphocytes have been known to accumulate at the site of inflammation at least in part because of their prolonged survival. Corticosteroids are the most potent anti-inflammatory agent used for treating asthma. They inhibit the prolonged survival of eosinophils and lymphocytes directly by inducing apoptosis and indirectly by suppressing the release of cytokines supporting their survival. Theophylline, a classical bronchodilator, has been reported to have anti-inflammatory effects. Surprisingly, theophylline inhibited the prolonged survival of eosinophils in the presence of IL-5 in vitro by means of induction of apoptosis. Lymphocytes also undergo apoptosis in the presence of theophylline. One of the mechanisms for theophylline to induce apoptosis in eosinophils and lymphocytes is to elevate intracellular cyclic adenosine monophosphate because phosphodiesterase inhibitors and adenylate cyclase activators, which increase intracellular cyclic adenosine monophosphate, can cause apoptosis in those cells. Induction of apoptosis is beneficial in allergic inflammation, and the use of corticosteroids and theophylline in combination may be appropriate to induce apoptosis in eosinophils and lymphocytes.

Adrenal Cortex Hormones↗
PubMed1999

Chemical modification of apomorphine to discover sigma ligands: 6H-dibenzo[b,d]pyran and carbazole analogues.

It seems that many sigma ligands have been designed from known sigma ligands. We focused on a difference in structural flexibility between haloperidol and apomorphine, and studied chemical modification of apomorphine, a compound with high affinity for dopamine D2 receptors but not for sigma receptors, for discovery of sigma ligands. The first modification yielded good results with 6H-dibenzo[b,d]pyran analogues with weak affinity for sigma receptors but not D2 receptors. Furthermore, carbazole analogues, compounds designed from 6H-dibenzo[b,d]pyran analogues, potentially acted at sigma receptors with high selectivity. This paper describes the design, synthesis and sigma/D2 selectivity of 6H-dibenzo[b,d]pyran and carbazole analogues.

Animals↗
PubMed1999

Transcriptional analysis of two endoinulinase genes inuA and inuB in Aspergillus niger and nucleotide sequences of their promoter regions.

Aspergillus niger 12 contained two copies of endoinulinase genes (inuA and inuB) in the genome (K. Ohta et al., Biosci. Biotechnol. Biochem., 62, 1731-1738, 1998). The inuA- and inuB-specific DNA probes were constructed according to the respective 3'-noncoding sequences that diverged from each other. Poly(A)+ RNA was prepared from mycelia grown on inulin, fructose, or glucose in submerged culture. Three endoinulinase cDNA sequences that corresponded to the coding regions and their 5'- and 3'-flanking regions were obtained by reverse transcription and subsequent polymerase chain reaction. Southern blot analysis revealed that the amplified cDNA 3'-noncoding sequences hybridized to the inuB probe but not to the inuA probe, regardless of the carbon source. The data suggest that only the inuB gene was transcribed constitutively. Four distinct 5' ends of the transcripts were observed at positions -80(A), -72(G), -69(A), and -65(A) from the start codon. The inuB mRNAs were polyadenylated at various sites between 94 and 297 bp downstream of the stop codon. We have determined the nucleotide sequences of the 1201- and 1017-bp 5'-noncoding regions of the inuA and inuB genes, respectively. The inuB promoter region included a putative TATA box at -116 (TATATA).

Journal Article↗