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Biomedical subjects

T Okuda

Publications and source records attributed to T Okuda.

At least 55 records · Page 3Linked to original sources
PubMed2001

Effect of long-term, low-dose acyclovir suppressive therapy on susceptibility to acyclovir and frequency of acyclovir resistance of herpes simplex virus type 2.

We have examined the susceptibility to acyclovir and frequency of acyclovir-resistant viruses in herpes simplex virus type (HSV) 2 clones isolated directly from genital lesions of 11 patients who had taken suppressive therapy (200 mg/day) for 1-9 years and 15 patients naive to acyclovir. Suppressive therapy significantly reduced the incidence of recurrence and the severity of the skin lesions. HSV samples from genital lesions were directly inoculated into Vero cells, and viral clones were isolated in the absence and presence of 10 microg/ml acyclovir. Five-hundred-and-ninety-two clones, isolated in the absence of acyclovir, were subjected to the acyclovir susceptibility test, and 155 clones isolated in the presence of acyclovir were analysed for the mechanisms of resistance to acyclovir. There were no significant differences in the susceptibility to acyclovir, the frequency of acyclovir-resistant virus and the ratio of thymidine kinase-deficient viruses in acyclovir-resistant viruses between the two groups. The frequency of acyclovir-resistant clones was about three per 10000 plaque forming units (PFU), and genital lesions contained up to 3x10(6) PFU of replicating virus in the specimens from the patients with genital herpes with or without acyclovir-suppressive therapy. Thus, the low dose of acyclovir suppressive therapy did not affect the susceptibility to acyclovir or increase the frequency of acyclovir-resistant viruses in the genital lesions.

Acyclovir↗
PubMed2001

Involvement of potassium channels in spinal antinociceptions induced by fentanyl, clonidine and bethanechol in rats.

In the central nervous systems, intracellular and extracellular movement of potassium ions plays an important role in regulating neuronal excitability and the release of neurotransmitters. The purpose of our study was to determine whether nicorandil (adenosine triphosphate-sensitive K+ channel opener) exerts antinociceptive effects by itself or in combination with fentanyl, clonidine and bethanechol and whether glibenclamide (adenosine triphosphate-sensitive K+ channel blocker) and charybdotoxin (Ca2+-activated K+ channel blocker) may antagonize the antinociceptive action of fentanyl, clonidine and bethanechol. Antinociceptive effects were assessed using the tail-flick test in rats. Nicorandil (100 microg) and antinociceptively ineffective doses of fentanyl (1 microg), clonidine (2.5 microg) or bethanechol (10,ug) were coadministered intrathecally (i.t.). Glibenclamide (100 microg) or charybdotoxin (2.5 ng) were administered i.t. at 5 min before each effective dose of fentanyl (2.5 microg), clonidine (10 microg) or bethanechol (40 microg). The present findings demonstrated that i.t. administration of nicorandil alone exerted no influence on the tail-flick latency. However, concomitant administrations of antinociceptively inactive doses of fentanyl, clonidine or bethanechol with nicorandil elicited significant suppression of the thermonociceptive response. Also, each antinociception induced by fentanyl, clonidine or bethanechol was partially antagonized by both glibenclamide and charybdotoxin. These findings showed that activation of the K+ channel might enhance the antinociceptive effects of fentanyl, clonidine and bethanechol.

Adenosine Triphosphatases↗
PubMed2001

Aurantiamide acetate, a selective cathepsin inhibitor, produced by Aspergillus penicilloides.

Aurantiamide acetate was isolated from the fermentation broth of Aspergillus penicilloides for the first time. Aurantiamide acetate inhibited cysteine proteinases, in particular, cathepsin L (3.4.22.15) and B (3.4.22.1) with IC50 of 12 microM and 49 microM, respectively. In the adjuvant-arthritic rat model, subcutaneously administered 10 mg/kg body weight of this compound suppressed hind paw swelling.

Aspergillus↗
PubMed2001

Regulation of corpora allata in females of Pyrrhocoris apterus (Heteroptera) (a mini-review).

Mechanisms for the transduction of photoperiodic and food signals to the corpus allatum (CA) are described. The focus of this paper is on the control of the CA by the brain in adult females of the firebug, Pyrrhocoris apterus. By using surgical interventions to the neuroendocrine complex of brain-subesophageal ganglion-corpora cardiaca-CA (BR-SG-CC-CA) in vivo and in vitro we were able to identify two regulatory pathways. (1) Slow regulation of the CA activity (stimulation or inhibition) needs a relatively long period of time to be accomplished (several d) in vivo and is associated with changes of the gland cell volume and ultrastructure. The stimulated or inhibited activity of the CA is maintained during short-term incubation of the isolated CA in vitro. (2) Fast inhibition of the CA activity is reversible during short-term incubation in vitro; the CA can be switched from lower to higher activity and vice versa, depending on the presence or absence of the BR-SG in the medium. Both slow and fast regulatory factors originate in the pars intercerebralis of the brain and in intact neuroendocrine complex they reach the CA via nerves. A slow inhibitor, induced by short d, causes reproductive diapause. A fast inhibitor prevents ovarian maturation in starved nondiapausing females. A slow stimulator, induced by feeding under long d, overcomes the fast inhibition of the CA, thereby stimulating vitellogenesis. Food signals are transmitted to the brain via humoral pathways.

Animals↗
PubMed2001

TMC-69, a new antitumor antibiotic with Cdc25A inhibitory activity, produced by Chrysosporium sp. TC1068. Taxonomy, fermentation and biological activities.

A new antibiotic designated TMC-69 has been isolated from the fermentation broth of a fungal strain Chrysosporium sp. TC 1068. TMC-69 exhibited moderate in vitro cytotoxic activity. TMC-69-6H, a derivative of TMC-69 prepared by hydrogenation, possessed more potent in vitro cytotoxicity than TMC-69, and exhibited in vivo antitumor activity against murine P388 leukemia and B16 melanoma. TMC-69-6H was found to specifically inhibit Cdc25A and B phosphatases.

Animals↗
PubMed2001

TMC-205 a new transcriptional up-regulator of SV40 promoter produced by an unidentified fungus. Fermentation, isolation, physico-chemical properties, structural determination and biological activities.

A new transcriptional up-regulator designated TMC-205 was discovered from the fermentation broth of an unidentified fungal strain TC 1630 by using an SV40 promoter-luciferase reporter assay. Based on spectroscopic analyses, its structure was determined to be (E)-6-(3-methyl-1,3-butadienyl)- H-indole-3-carboxylic acid. Expression of the luciferase activity was activated ca. 2-, 4-, and 6-fold by 1, 10, and 100 microM TMC-205, respectively. TMC-205 activated the transcriptional activity in a manner dependent on the presence of the enhancer element of SV40 in its promoter region.

Chemical Phenomena↗
PubMed2001

Susceptibility to acyclovir of herpes simplex virus isolates obtained between 1977 and 1996 in Japan.

The susceptibility of genital herpes to acyclovir (ACV) in immunocompetent women was examined, as was the frequency of ACV-resistant viruses by analyzing 56 clinical isolates in Japan between 1977 and 1996. The mean susceptibilities of herpes simplex virus (HSV) type 1 and type 2 were 0.13+/-0.74 and 0.42+/-0.14 microg/ml, respectively, assessed by the 50% inhibitory concentration of plaque formation. The susceptibility to ACV of clinical isolates did not changed since 1977, and also that of nine pairs of HSV-1 and HSV-2 isolates was not affected by ACV treatment. In order to characterize the change in the virus population, the quantitation of the ACV-resistant virus in 10(4) plaque forming units (PFU) of clinical isolates was adopted. The mean frequencies of ACV-resistant viruses per 10(4) PFU for all strains of HSV-1 and HSV-2 were 0.31+/-0.41 and 9.74+/-14.83, respectively, and were not influenced by ACV treatment. Additionally, the phenotypes of ACV-resistance were not influenced by ACV treatment, and more than 90% of ACV-resistant viruses were found to be thymidine kinase-deficient. This study characterized clinical isolates with respect to ACV susceptibility as a population and the quantitative and qualitative characterization of ACV-resistant virus in the virus population of clinical isolates was also studied. The susceptibility of isolates from genital lesions, the frequency of ACV-resistant viruses, and also the phenotypic characterization of ACV-resistant viruses was maintained between 1977 and 1996, even after the introduction of ACV treatment for genital herpes in Japan.

Acyclovir↗
PubMed2001

[Anesthetic management of a patient with blood coagulation factor XII deficiency].

A 36-yr-old pregnant woman with blood coagulation factor XII deficiency was scheduled to undergo cesarean section. Preoperative blood coagulation scan revealed prolonged activated partial thrombin time of 105.6 s (control, 30.3 s), and a decrease in factor XII level of 3% (normal; 70-120%). Other examinations such as prothrombin time, platelet count and bleeding time were within normal limits. But she reported no history of bleeding. Before the operation, we discussed with obstetricians whether fresh frozen plasma (FFP) should be administered, or not. According to a report, a patient with factor XII deficiency can undergo major surgery without plasma replacement therapy. But another study showed that 15-30% of the factor XII activity was needed for hemostasis. We, therefore, administered 4 units of fresh frozen plasma before the operation. The operation was performed with general anesthesia uneventfully. Generally, a patient with factor XII deficiency has no clinical bleeding problems and unnecessary FFP administration may cause infection. Therefore it is not necessary to administer FFP to this patient.

Adult↗
PubMed2001

Selective isolation and study on the global distribution of the genus Planobispora in soils.

Planobispora strains, including the type strain, produced abundant sporangia on humic acid-vitamin gellan gum medium when more than 50 colonies grew on a plate. However, these strains did not produce sporangia on the aerial mycelium, a diagnostic characteristic of this genus, when fewer than 20 colonies grew on a plate. Trace salts, such as FeSO4 x 7H2O, MnCl2 x 4H2O, ZnSO4 x 7H2O, and NiSO4 x 6H2O, stimulated sporangium formation of Planobispora strains. Better sporangium formation of Planobispora strains was observed on the humic acid-trace salts gellan gum medium at pH 9.0 than at neutral pH. Moreover, an alkaline medium repressed the growth of three out of six Streptomyces strains so that this condition was effective for selective isolation of Planobispora strains. An alkaline flooding solution of skim milk, five antimicrobial agents, and dry heat treatment at 90 degrees C for 60 min were effective for selective isolation. Using these techniques, we examined the distribution of Planobispora strains by using 1467 soil samples collected from Japan and other parts of the world. One hundred and nineteen Planobispora strains were isolated from 51 soil samples (3.5% of the samples tested) that were collected in Ecuador, Egypt, French Guiana, India, and Madagascar. Planobispora strains were recovered only in tropical and subtropical soils. To our knowledge, this is the first record that Planobispora strains have been isolated from locations other than Venezuela, Namibia, or South Africa.

Actinomycetales↗
PubMed2001

[Characterization of cryoglobulin, M protein, low molecular weight IgM in a patient with chronic hepatitis C and type II mixed cryoglobulinemia].

The common extrahepatic manifestation of hepatitis C virus(HCV) infection is mixed cryoglobulinemia. We have analyzed serum cryoglobulin, IgM and various antibody activities from a patient with chronic hepatitis C and type II cryoglobulinemia. Cryoprecipitates were consisted of polyclonal IgG and monoclonal IgM-kappa with rheumatoid factor activity. About 20% of total IgM was found to be low molecular weight IgM by gel-filtration and SDS-PAGE. The anti-streptolysin O(ASO) activity measured by Latex agglutination method was found to be markedly elevated despite normal activity by Rantz-Randell method. The patient's serum has revealed to react against bovine gamma globulin, which crosslinked streptolysin O to Latex particles, in a nonspecific manner. Phenotypic analysis of the surface markers on abnormal lymphoid cells from peripheral blood and bone marrow showed monoclonal expansion of B-cell lineage by flow cytometry. The patient was treated with interferon-alpha, which resulted in an improvement of liver dysfunction, decreased amounts of cryoglobulin and IgM. It was concluded that the patient has suffered from lymphoproliferative disorder, namely HCV infection-associated primary macroglobulinemia.

Aged↗
PubMed2000

Molecular cloning and characterization of GalNAc 4-sulfotransferase expressed in human pituitary gland.

We have previously cloned chondroitin-4-sulfotransferase (C4ST) cDNA from mouse brain. In this paper, we report cloning and characterization of GalNAc 4-sulfotransferase (GalNAc4ST), which transfers sulfate to position 4 of the nonreducing terminal GalNAc residue. The obtained cDNA contains a single open reading frame that predicts a type II transmembrane protein composed of 424 amino acid residues. Identity of the amino acid sequence between GalNAc4ST and human C4ST was 30%. When the cDNA was transfected in COS-7 cells, sulfotransferase activity toward carbonic anhydrase VI was overexpressed but no sulfotransferase activity toward chondroitin or desulfated dermatan sulfate was increased over the control. Sulfation of carbonic anhydrase VI by the recombinant GalNAc4ST occurred at position 4 of the GalNAc residue of N-linked oligosaccharides. The recombinant GalNAc4ST transferred sulfate to position 4 of GalNAc residue of p-nitrophenyl GalNAc, indicating that this sulfotransferase transfers sulfate to position 4 at the nonreducing terminal GalNAc residue. Dot blot analysis showed that the message of GalNAc4ST was expressed strongly in the human pituitary, suggesting that the cloned GalNAc4ST may be involved in the synthesis of the nonreducing terminal GalNAc 4-sulfate residues found in the N-linked oligosaccharides of pituitary glycoprotein hormones.

Amino Acid Sequence↗
PubMed2000

Critical behavior of metal-insulator transition in La1-(x)Sr(x)VO3.

Critical behavior of the metal-insulator transition (MIT) coupled with spin/orbital correlations has been investigated for single crystals of La1-(x)Sr(x)VO3. In the paramagnetic (PM) metal phase (x > 0.260), the precursor to the MIT manifests itself as an enhancement of carrier effective mass. In the antiferromagnetic (AF) metal phase (0.178 < or = x < or = 0.260), the carrier density decreases and the correlation of the orbital seems to evolve towards the MIT (x = 0.178). In the AF insulating phase (x < 0.178), the distinct first-order structural phase transition occurs with the decrease of temperature, perhaps concomitantly with the orbital ordering.

Journal Article↗
PubMed2000

Immunomodulation for intestinal transplantation by allograft irradiation, adjunct donor bone marrow infusion, or both.

BACKGROUND: The passenger leukocytes in the intestine have a lineage profile that predisposes to graft-versus-host disease (GVHD) in some animal models and have inferior tolerogenic qualities compared with the leukocytes in the liver, other solid organs, and bone marrow. Elimination by ex vivo irradiation of mature lymphoid elements from the bowel allografts is known to eliminate the GVHD risk. We hypothesized that infusion of donor bone marrow cells (BMC) in recipients of irradiated intestine would improve tolerogenesis without increasing the risk of GVHD. METHODS: Orthotopic small intestine transplantation was performed with the GVHD-prone Lewis (LEW)-to-Brown Norway (BN) combination and the reverse GVHD-resistant BN-to-LEW model under a short course of tacrolimus treatment (1 mg/kg/day, days 0-13, 20, 27). Grafts were irradiated ex vivo, using a 137Cs source. In selected experimental groups, donor BMC (2.5 x 10(8)) were infused on the day of small intestine transplantation. RESULTS: The unmodified LEW intestine remained intact, whether transplanted alone or with adjunct donor BMC infusion, but all of the BN recipients died of GVHD after approximately 2 months. Intestinal graft irradiation (10 Gy) effectively prevented the GVHD and prolonged survival to 92.5 days, but all of the BN recipients died with chronic rejection of the LEW grafts, which was prevented by infusion of adjunct donor BMC without causing GVHD. In the GVHD-resistant reverse strain direction (BN-->LEW), all intestinal recipients treated for 27 days with tacrolimus survived > or =150 days without regard for graft irradiation or adjunct BMC, but chronic rejection was severe in the irradiated intestine, moderate in the unaltered graft, and least in the irradiated intestine transplanted with adjunct BMC. Mild arteritis in the 150 day allografts of both strain combinations (i.e., LEW--> BN and BN-->LEW) may have been irradiation associated, but this was prevented when weekly doses of tacrolimus were continued for the duration of the experiment rather than being stopped at 27 days. CONCLUSIONS: Recipients are protected from GVHD by irradiating intestinal allografts, but the resulting leukocyte depletion leads to chronic rejection of the transplanted bowel. The chronic rejection is prevented with adjunct donor BMC without causing GVHD. Although application of the strategy may be limited by the possibility of radiation injury, the results are consistent with the paradigm that we have proposed to explain organ-induced graft acceptance, tolerance, and chronic rejection.

Animals↗
PubMed2000

Functional characterization of the human high-affinity choline transporter.

Na(+)-dependent, high-affinity choline uptake in cholinergic neurons is the rate-limiting step in acetylcholine synthesis. Here we report the molecular cloning and functional characterization of the human high-affinity choline transporter (hCHT1). The hCHT1 exhibits significant homology with known members of the Na(+)-dependent glucose transporter family, but not with members of the neurotransmitter transporter family. The human CHT1 gene is 25 kb in length with 9 exons and was assigned to chromosome II at position IIq11-12. Northern blot analysis showed that a 5.4 kb hCHT1 transcript was expressed exclusively in tissues containing cholinergic neurons. When expressed in Xenopus oocytes, the human clone induced Na(+)- and Cl(-)-dependent, high-affinity choline uptake, which was sensitive to the specific inhibitor hemicholinium-3, with a K(i) of 1.3 nM. The hCHT1-mediated choline uptake increased with increasing concentrations of choline, Na(+) and Cl(-), with EC(50) values of 2.0 microM, 76 mM, and 48 mM, and with apparent Hill coefficients of 1, 2.5 and 2.3, respectively.

Acetylcholine↗
PubMed2000

v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells.

We investigated the effect of cell transformation by v-src on the expression and tyrosine phosphorylation of SHPS-1, a putative docking protein for SHP-1 and SHP-2. We found that transformation by v-src virtually inhibited the SHPS-1 expression at mRNA level. While nontransforming Src kinases including c-Src, nonmyristoylated forms of v-Src had no inhibitory effect on SHPS-1 expression, transforming Src kinases including wild-type v-Src and chimeric mutant of c-Src bearing v-Src SH3 substantially suppressed the SHPS-1 expression. In cells expressing temperature sensitive mutant of v-Src, suppression of the SHPS-1 expression was temperature-dependent. In contrast, tyrosine phosphorylation of SHPS-1 was rather activated in cells expressing c-Src or nonmyristoylated forms of v-Src. SHPS-1 expression in SR3Y1 was restored by treatment with herbimycin A, a potent inhibitor of tyrosine kinase, or by the expression of dominant negative form of Ras. Contrary, active form of Mekl markedly suppressed SHPS-1 expression. Finally, overexpression of SHPS-1 in SR3Y1 led to the drastic reduction of anchorage independent growth of the cells. Taken together, our results suggest that the suppression of SHPS-1 expression is a pivotal event for cell transformation by v-src, and the Ras-MAP kinase cascade plays a critical role in the suppression.

3T3 Cells↗
PubMed2000

Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase.

A full-length cDNA encoding a novel protein was isolated and sequenced from a human hepatocellular cDNA library. This cDNA consists of 7037 base pairs and has a predicted open reading frame encoding 1924 amino acids. It possesses an RNA-helicase motif containing a DEXH-box in its amino-terminus and an RNase motif in the carboxy-terminus. From a striking homology to Caenorhabditis elegans K12H4.8, it might be a human homolog of the K12H4.8. PCR-based mapping with both a monochromosomal hybrid panel and radiation hybrid cell panels placed the gene to human chromosome 14q31 near the marker D14S605.

Amino Acid Sequence↗