Mexiletine is effective on segmental hyperhidrosis: report of two cases.
Explore the source record for details and available documents.
Administration, Oral↗
Biomedical subjects
T Yokota
Publications and source records attributed to T Yokota.
Age and stage dependency of estrogen receptor expression by lymphocyte precursors.
Sex steroids negatively regulate B lymphopoiesis in adult mice. Paradoxically, lymphocytes arise during fetal life, when estrogen levels are high and maternal lymphopoiesis is suppressed. Here we demonstrate that embryonic B lymphopoiesis was unaffected by estrogen, but sensitive to glucocorticoids. Both fetal and adult precursors contained glucocorticoid receptor transcripts, but only adult precursors expressed estrogen receptor alpha and beta together with the androgen receptor. Fetal hematopoietic cells did not efficiently acquire functional estrogen receptors after transplantation to irradiated adult mice. Sex steroid receptors were also expressed in a stage- and developmental age-dependent fashion in human precursors. A developmental switch in responsiveness of hematopoietic cells to sex steroids may be essential for formation of the immune system.
Age Factors↗
Delayed-onset ataxia in mice lacking alpha -tocopherol transfer protein: model for neuronal degeneration caused by chronic oxidative stress.
alpha-Tocopherol transfer protein (alpha-TTP) maintains the concentration of serum alpha-tocopherol (vitamin E), one of the most potent fat-soluble antioxidants, by facilitating alpha-tocopherol export from the liver. Mutations of the alpha-TTP gene are linked to ataxia with isolated vitamin E deficiency (AVED). We produced a model mouse of AVED by deleting the alpha-TTP gene, which showed ataxia and retinal degeneration after 1 year of age. Because the brain alpha-TTP functions in maintaining alpha-tocopherol levels in the brain, alpha-tocopherol was completely depleted in the alpha-TTP(-/-) mouse brain, and the neurological phenotype of alpha-TTP(-/-) mice is much more severe than that of wild-type mice when maintained on an alpha-tocopherol-deficient diet. Lipid peroxidation in alpha-TTP(-/-) mice brains showed a significant increase, especially in degenerating neurons. alpha-Tocopherol supplementation suppressed lipid peroxidation and almost completely prevented the development of neurological symptoms. This therapy almost completely corrects the abnormalities in a mouse model of human neurodegenerative disease. Moreover, alpha-TTP(-/-) mice may prove to be excellent animal models of delayed onset, slowly progressive neuronal degeneration caused by chronic oxidative stress.
Animals↗
[von Recklinghausen disease associated with intrahepatic cholangiocarcinoma and ampullary carcinoid].
Explore the source record for details and available documents.
Bile Duct Neoplasms↗
Alkane oxidation with air catalyzed by lipophilic N-hydroxyphthalimides without any solvent.
Explore the source record for details and available documents.
Journal Article↗
Cloning of full-length genomic DNA encoding human FcepsilonRI alpha-chain and its transcriptional regulation.
Two novel exons, named exon 1A and exon 2A, were found at 18.4 and 12.6 kb upstream from the exon known as the first exon of human FcepsilonRI alpha-chain gene. Transcription from the promoter present in the upstream of exon 1A was decreased by mutations introduced into the "first intron" between exon 1A and exon 2A, suggesting the presence of an intronic regulatory element in the intron. Consistent with this, electrophoretic mobility shift assay revealed the presence of a nuclear factor which bound the region in FcepsilonRI alpha-chain positive cells.
Base Sequence↗
Endogenous nitric oxide-mediated relaxation and nitrinergic innervation in the rabbit prostate: the changes with aging.
BACKGROUND: Nitric oxide (NO) plays the key role in the non-adrenergic non-cholinergic (NANC) nerve-mediated relaxation of prostate. We tried to determine whether nitrinergic innervation of the prostate is reduced with aging, and whether a reduction of this innervation alters the relaxant properties of prostatic tissue. METHODS: The prostate isolated from young rabbits at the age of 3 months and aged rabbits at the age of 24 months was used. Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of prostate. Nitrinergic nerves were identified histochemically by the presence of NADPH diaphorase reactivity. RESULTS: The prostate weighed 0.34 +/- 0.06 g in the young and 0.78 +/- 0.13 g in the aged (P < 0.01). Electrical stimulation caused frequency-dependent relaxation that was inhibited by N-nitro-L-arginine and increased by L-arginine. Maximum relaxant rates of noradrenaline-induced tone were 41.3 +/- 1.8% and 22.7 +/- 0.6% in the young and the aged (P < 0.01), respectively. Exogenous NO caused concentration-dependent relaxation of the prostate. Both relaxation induced by electrical stimulation and exogenous NO were inhibited by LY83583 (a guanylate cyclase inhibitor). In all specimens, NADPH diaphorase activity was observed in the smooth muscle layer of the prostatic stroma and capsule. However, NADPH diaphorase positive nerves were significantly less in the aged than in the young (P < 0.01). CONCLUSIONS: As a result of these findings, it is suggested that both NO-mediated relaxation and nitrinergic innervation are reduced with aging in this animal model.
Aging↗
Inhibitory effect of oxcarbazepine on high-frequency firing in peripheral nerve fibers.
We assessed the effects of oxcarbazepine, an antiepileptic derivative of carbamazepine, on discharges in single cutaneous afferent fibers produced by repetitive high-frequency stimulation (mimicking the abnormal excitation of peripheral nerves in neuropathic pain and paresthesia). After intravenous administration of oxcarbazepine, the later responses in the train dropped out without the earlier ones being affected and, thus, the total number of spikes decreased. The latency of the responses to an individual pulse was unchanged. These results, which indicate that oxcarbazepine inhibits the generation of high-frequency firing without affecting impulse conduction, suggest that this drug may be useful against neuropathic pain and paresthesia.
Animals↗
A novel chordin-like protein inhibitor for bone morphogenetic proteins expressed preferentially in mesenchymal cell lineages.
Chordin is a bone morphogenetic protein (BMP) inhibitor that has been identified as a factor dorsalizing the Xenopus embryo. A novel secreted protein, CHL (for chordin-like), with significant homology to chordin, was isolated from mouse bone marrow stromal cells. Injection of CHL RNA into Xenopus embryos induced a secondary axis. Recombinant CHL protein inhibited the BMP4-dependent differentiation of embryonic stem cells in vitro and interacted directly with BMPs, similar to chordin. However, CHL also weakly bound to TGFbetas. In situ hybridization revealed that the mouse CHL gene, located on the X chromosome, was expressed predominantly in mesenchyme-derived cell types: (1) the dermatome and limb bud mesenchyme and, later, the subdermal mesenchyme and the chondrocytes of the developing skeleton during embryogenesis and (2) a layer of fibroblasts/connective tissue cells in the gastrointestinal tract, the thick straight segments of kidney tubules, and the marrow stromal cells in adults. An exception was expression in the neural cells of the olfactory bulb and cerebellum. Interestingly, the spatiotemporal expression patterns of CHL were distinct from those of chordin in many areas examined. Thus, CHL may serve as an important BMP regulator for differentiating mesenchymal cells, especially during skeletogenesis, and for developing specific neurons.
Alternative Splicing↗
Identification, tissue expression, and chromosomal position of a novel gene encoding human ubiquitin-conjugating enzyme E2-230k.
Through large-scale human genome mapping and sequencing of a region at chromosome 17q25.1 that is of particular interest because genes associated with breast, ovarian, and esophageal cancer are likely to be located there, we isolated the cDNA of a novel member of the family of ubiquitin-conjugating enzymes. The predicated peptide showed 97% identity in amino-acid sequence to murine ubiquitin-conjugating enzyme E2-230k (Mus UBE2-230k). The human cDNA consisted of 4878 nucleotides with an open reading frame encoding 1138 amino acids; the approximately 5 kb transcript was expressed predominantly in skeletal muscle and heart. The predicted UBE2-230k peptide contained a motif typical of the UBC domain that has been implicated in the ubiquitin-dependent proteolytic system and related pathways.
Amino Acid Sequence↗
Three-dimensional estimation of the distribution and size of putative functional units in rat gustatory cortex as assessed from the inter-neuronal distance between two neurons with correlative activity.
Two neurons recorded simultaneously in rat gustatory cortex often show, when the oral mucosa is stimulated with effective taste solutions, correlative activities (CAs), which can be quantified with a cross-correlation technique. It has been suggested that the CAs are involved in taste quality discrimination and the neuron pairs with CA (CA pairs) may function as a unit (putative functional unit). The present experiment was undertaken (1) to determine the three-dimensional size of putative functional units in rat gustatory cortex on the basis of the interneuronal distance (IND) in individual CA pairs, and (2) to examine to what extent the CA is related to the intrapair similarity in taste responses. The findings were as follows: (1) The CAs occurred in 30 out of 55 pairs with INDs < or =270 microm and often at INDs <100 microm. (2) The numbers of putative functional units were calculated tentatively by using the longest or the mean INDs; at least 200 or over 4,000 units, respectively. (3) In the CA pairs, the "best taste" was identical (homo-type) in many pairs, the "taste profiles" were often similar, and the temporal courses of taste responses resembled each other in more than one half of the pairs. A possible role of hetero-type pairs was discussed. (4) In a small number of cases, troughs were observed in the CCs, suggesting the involvement of local inhibitory neurons. In conclusion we point out that nearby neurons are prone to CA, if (1) their best tastes are identical, (2) their taste profiles are similar, and (3) the temporal patterns of taste response resemble each other.
Action Potentials↗
Molecular cloning, tissue expression, and chromosomal assignment of a novel gene encoding a subunit of the human signal-recognition particle.
Human cancers derived from breast, esophageal, or ovarian tissues frequently show allelic losses on chromosome band 17q25. Moreover, a locus responsible for hereditary focal nonepidermolytic palmoplantar keratoderma, a condition associated with esophageal cancer (TOC; tylosis with oesophageal cancer), has been mapped to the same band. During efforts to sequence, by shotgun methods, a 1-Mb target region that we had defined as the DNA segment harboring the putative tumor suppressor gene(s) involved in these events, we identified a novel cDNA. The full-length cDNA is 2495bp long and is expressed predominantly in skeletal muscle, heart, kidney, and placenta. The predicted product, a 627-amino-acid protein, exhibited significant sequence homology to the canine 68-kd subunit of the signal recognition particle that has been implicated in the transport of secreted and membrane proteins to the endoplasmic reticulum for proper processing. We confirmed the location of this gene at chromosome 17q25.1 by radiation-hybrid mapping and by fluorescence in situ hybridization.
Amino Acid Sequence↗
Accumulation of 6-deoxocathasterone and 6-deoxocastasterone in Arabidopsis, pea and tomato is suggestive of common rate-limiting steps in brassinosteroid biosynthesis.
To gain a better understanding of brassinosteroid biosynthesis, the levels of brassinosteroids and sterols related to brassinolide biosynthesis in Arabidopsis, pea, and tomato plants were quantified by gas chromatography-selected ion monitoring. In these plants, the late C-6 oxidation pathway was found to be the predominant pathway in the synthesis of castasterone. Furthermore, all these plant species had similar BR profiles, suggesting the presence of common biosynthetic control mechanisms. The especially high levels of 6-deoxocathasterone and 6-deoxocastasterone may indicate that their respective conversions to 6-deoxoteasterone and castasterone are regulated in planta and hence are important rate-limiting steps in brassinosteroid biosynthesis. Other possible rate-limiting reactions, including the conversion of campestanol to 6-deoxocathasteonre. are also discussed. Tomato differs from Arabidopsis and pea in that tomato contains 28-norcastasterone as a biologically active brassinosteroid, and that its putative precursors, cholesterol and its relatives are the major sterols.
Arabidopsis↗
Endogenous gibberellins in immature seeds of Prunus persica L.: identification of GA(118), GA(119), GA(120), GA(121), GA(122) and GA(126).
The endogenous gibberellins in immature seeds of Prunus persica were analyzed by gas chromatography-mass spectrometry. Eleven known gibberellins, GA(3), GA(9), GA(17), GA(19), GA(30), GA(44), GA(61), GA(63), GA(87), GA(95) and GA(97) were identified. Additionally, several hitherto unknown gibberellins were detected and their putative structures were verified by synthesis of the authentic gibberellins. These gibberellins were then assigned trivial numbers, e.g. 1alpha-hydroxy GA(20) (GA(118)), 1alpha-hydroxy GA(9) (GA(119)), 1,2-didehydro GA(9) (GA(120)), 1,2-didehydro GA(70) (GA(121)), 1,2-didehydro GA(69) (GA(122)) and 1,2-didehydro GA(77) (GA(126)). GA(118) and GA(119) were the first 1alpha-hydroxy gibberellins identified from higher plants. The above profile of 1,2-didehydro gibberellins suggests that 1,2-dehydrogenation might occur prior to 3beta-hydroxylation in biosynthesis of GA(3), GA(30) and GA(87) in immature seeds of P. persica.
Gas Chromatography-Mass Spectrometry↗
Synthesis and biological activity of 26-norbrassinolide, 26-norcastasterone and 26-nor-6-deoxocastasterone.
26-Norbrassinolide, identified as a metabolite of brassinolide in cultured cells of the liverwort, Marchantia polymorpha, as well as 26-norcastasterone and 26-nor-6-deoxocastasterone were synthesized. Synthesis of these new brassinosteroids was conducted by employing the orthoester Claisen rearrangement and asymmetric dihydroxylation as key reactions. The modified rice lamina inclination test indicated that these three 26-norbrassinosteroids were less active than their corresponding C28 brassinosteroids. Growth-promoting activities were also examined by using the brassinosteroid-deficient, dwarf mutant lkb of garden pea (Pisum sativum L.). In this assay, 26-norbrassinolide was as effective as brassinolide and 26-norcastasterone was more effective than castasterone although 26-nor-6-deoxocastasterone was much less effective than 6-deoxocastasterone. Therefore, removal of C-26 of brassinosteroids does not necessarily reduce the biological activity. The role of C-26 removal in Marchantia cells remains unclear.
Plants↗
Roots and shoots of tomato produce 6-deoxo-28-norcathasterone, 6-deoxo-28-nortyphasterol and 6-deoxo-28-norcastasterone, possible precursors of 28-norcastasterone.
Roots and shoots of tomato (Lycopersicon esculentum) were investigated for the occurrence of biosynthetic precursors of 28-norcastasterone, a C27 brassinosteroid that we have shown to be present in shoots of tomato. A series of putative precursors, including 6-deoxo-28-norcathasterone, 6-deoxo-28-norteasterone, 3-dehydro-6-deoxo-28-norteasterone, 6-deoxo-28-nortyphasterol and 6-deoxo-28-norcastasterone, were synthesized and used as GC-MS standards, resulting in the identification of 6-deoxo-28-norcathasterone, 6-deoxo-28-nortyphasterol and 6-deoxo-28-norcastasterone in both roots and shoots. These findings indicate that the biosynthesis of 28-norcastasterone may parallel that of castasterone. The endogenous levels of brassinosteroids differed between roots and shoots, indicating that the biosynthesis of brassinosteroids is differently regulated between these tissues. Regulation of root growth by brassinosteroids is also discussed.
Gas Chromatography-Mass Spectrometry↗
Antisense therapy of influenza.
The liposomally encapsulated and the free antisense phosphorothioate oligonucleotides (S-ODNs) with four target sites (PB1, PB2, PA, and NP) were tested for their abilities to inhibit virus-induced cytopathogenic effects by a MTT assay using MDCK cells. The liposomally encapsulated S-ODN complementary to the sites of the PB2-AUG initiation codon showed highly inhibitory effects. On the other hand, the inhibitory effect of the liposomally encapsulated S-ODN targeted to PB1 was considerably decreased in comparison with those directed to the PB2 target sites. The liposomally encapsulated antisense phosphorothioate oligonucleotides exhibited higher inhibitory activities than the free oligonucleotides, and showed sequence-specific inhibition, whereas the free antisense phosphorothioate oligonucleotides were observed to inhibit viral absorption to MDCK cells. Therefore, the antiviral effects of S-ODN-PB2-AUG and PA-AUG were examined in a mouse model of influenza virus A infection. Balb/c mice exposed to the influenza virus A (A/PR/8/34) strain at dose of 100 LD(50)s were treated i.v. with various doses (5-40 mg/kg) of liposomally (Tfx-10) encapsulated PB2-AUG or PA-AUG before virus infection and 1 and 3 days postinfection. PB2-AUG oligomer treated i.v. significantly prolonged the mean survival time in days (MDS) and increased the survival rates with a dose-dependent manner. We demonstrate the first successful in vivo antiviral activity of antisense administered i.v. in experimental respiratory tract infections induced with influenza virus A.
Animals↗
Proximal motor conduction evaluated by transcranial magnetic stimulation in acquired inflammatory demyelinating neuropathies.
OBJECTIVES: To evaluate conduction abnormalities in the proximal motor nerve in patients with acquired inflammatory demyelinating neuropathies by transcranial magnetic stimulation (TMS). METHODS: TMS intensity and background voluntary contraction (BVC) to evoke maximal size of motor evoked potential (MEP) in hand muscle were investigated in 24 normal subjects. Effect of experimentally induced conduction block by injecting local anesthetics in the peripheral nerve on MEP size was also studied in two normal subjects. In 22 patients with inflammatory demyelinating neuropathies, maximal MEPs were recorded in the deteriorating and recovery stages of the illness. RESULTS: In normal subjects, the MEP became maximal with 30-50% of maximal BVC and at more than 80% the maximal stimulator output of the 2.0 T circular coil. The change in MEP size well reflected the degree of conduction block induced by local anesthetics. Findings for patients suggested conduction abnormalities proximal to axilla in 9 patients, and that the abnormal reduction of Erb CMAP was the result of submaximal stimulation, not true conduction block, in 3 patients. The increase in MEP/wrist CMAP ratio was better correlated with improvement in muscle strength than with change in the axilla or Erb CMAP/wrist CMAP ratio. CONCLUSIONS: Problems such as conduction abnormalities in the motor tract of the central nervous system could not fully be excluded, but we consider that maximal MEP size can be used to predict proximal motor nerve conduction abnormalities.
Action Potentials↗