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Biomedical subjects

H Fukui

Publications and source records attributed to H Fukui.

At least 145 records · Page 8Linked to original sources
PubMed1999

Development of primary hypothyroidism with the appearance of blocking-type antibody to thyrotropin receptor in Graves' disease in late pregnancy.

Spontaneous remission of Graves' disease with a decrease of thyroid stimulating antibody (TSAb) activity is commonly observed in pregnancy. In this article, however, a Graves' patient who developed primary hypothyroidism with an appearance of thyroid stimulation-blocking antibody (TSBAb) activity in late pregnancy is reported. A 25-year-old woman presented with clinical and biochemical hyperthyroidism with an elevation of 99mTcO4- thyroid uptake (4.7%; normal range, 0.7%-3.0%) and mildly elevated activity of thyrotropin-binding inhibitory immunoglobulin (TBII; 30.4%). She was euthyroid with normal TBII (8.0%) and TSAb (126%) before pregnancy, when the patient was taking a 5-mg daily dose of methimazole (MMI). MMI was stopped by the patient when she became pregnant. Subsequently, the patient progressed into primary hypothyroidism with a marked elevation of TBII activity (78.4%) in the third trimester of the pregnancy (at that time, TSAb activity was not detected). TSBAb measured 2 weeks later was detected at the activity of 85.0%. Replacement therapy was initiated with levothyroxine (LT4) (0.05-0.1 mg/day), which was discontinued on the 55th day postpartum because of the onset of mild thyrotoxicosis followed by short-term euthyroid state despite high TSBAb activity. Subsequently, because the patient developed primary hypothyroidism 5 months after delivery, replacement therapy with LT4 (0.1-0.125 mg/day) was readministered. Thus, it is suggested that the development of hypothyroidism with the appearance of TSBAb in Graves' patients can occur even in late pregnancy.

Adult↗
PubMed1999

Prognostic factors in severe alcoholic liver injury. Nara Liver Study Group.

Severe alcoholic liver injury has been relatively rare, but is gradually increasing in Japan. The clinical features and prognostic factors in severe alcoholic liver injury were retrospectively investigated in 105 patients, consisting of 3 with severe alcoholic hepatitis (SAH), 43 with cirrhosis with superimposed alcoholic hepatitis [liver cirrhosis (LC)+alcoholic hepatitis (AH)], 38 with AH, and 21 with alcoholic cirrhosis. Seven of the 105 patients (6.7%, 2 with SAH and 5 with LC+AH) died of hepatic failure. Patients with SAH showed severe hyperbilirubinemia, reduced hepatic biosynthetic capacity, and marked acute inflammatory reactions, and developed multiple organ failure, such as disseminated intravascular coagulation (DIC), renal failure, acute pancreatitis, or pneumonia. Two SAH patients died within 1 month, whereas five with LC+AH died within 77 days during the second episode of AH. In these nonsurvivors, the serum total bilirubin (T.Bil) level was not normalized, and the hepaplastin test (HPT), serum albumin, cholesterol, and platelet count were not markedly improved after the first episode of AH. In the survivors, elevation of AST lasted longer, and the improvement of T.Bil, hepatic biosynthetic capacity, and the platelet count were much less in patients with LC+AH than in those with AH. Multivariate analysis using the Cox proportional hazards model showed serum C-reactive protein (CRP) and DIC as significant independent prognostic factors among SAH, LC+AH, and AH groups. When factors related to multiple organ failure, such as DIC and renal failure, were excluded, T.Bil and CRP were selected as independent prognostic factors. In patients with LC+AH and AH, CRP, and HPT were shown to be significant independent prognostic factors. These results suggest that SAH with multiple organ failure, and another episode of AH in advanced LC with hyperbilirubinemia and reduced hepatic biosynthetic capacity, are indicative of an extremely poor prognosis in chronic alcoholics.

Adult↗
PubMed1999

Suppression of bacterial blight by a bacterial community isolated from the guttation fluids of anthuriums

Growth and survival of Xanthomonas campestris pv. dieffenbachiae in guttation fluids (xylem sap exuded from leaf margins) of anthuriums were suppressed by several bacterial strains indigenous to leaves of various anthurium cultivars. Inhibition of growth was not observed in filter-sterilized guttation fluids and was restored to original levels only by reintroducing specific mixtures of bacteria into filter-sterilized guttation fluids. The inhibitory effect was related to the species in the bacterial community rather than to the total numbers of bacteria in the guttation fluids. One very effective bacterial community consisted of five species isolated from inhibitory guttation fluids of two susceptible anthurium cultivars. The individual strains in this community had no effect on the pathogen, but the mixture was inhibitory to X. campestris pv. dieffenbachiae in guttation fluids. The populations of the individual strains remained near the initial inoculum levels for at least 14 days. The effect of the five inhibitory strains on reducing disease in susceptible anthurium plants was tested by using a bioluminescent strain of X. campestris pv. dieffenbachiae to monitor the progression of disease in leaves nondestructively. Invasion of the pathogen through hydathodes at leaf margins was reduced by applying the strain mixture to the leaves. When the strain mixture was applied directly to wounds created on the leaf margins, the pathogen failed to invade through the wounds. This bacterial community has potential for biological control of anthurium blight.

Journal Article↗
PubMed1999

Cell surface galactosylation is essential for nonsexual flocculation in Schizosaccharomyces pombe.

We have isolated fission yeast mutants that constitutively flocculate upon growth in liquid media. One of these mutants, the gsf1 mutant, was found to cause dominant, nonsexual, and calcium-dependent aggregation of cells into flocs. Its flocculation was inhibited by the addition of galactose but was not affected by the addition of mannose or glucose, unlike Saccharomyces cerevisiae FLO mutants. The gsf1 mutant coflocculated with Schizosaccharomyces pombe wild-type cells, while no coflocculation was found with galactose-deficient (gms1Delta) cells. Moreover, flocculation of the gsf1 mutant was also inhibited by addition of cell wall galactomannan from wild-type cells but not from gms1Delta cells. These results suggested that galactose residues in the cell wall glycoproteins may be receptors of gsf1-mediated flocculation, and therefore cell surface galactosylation is required for nonsexual flocculation in S. pombe.

Carbohydrates↗
PubMed1999

Suppression and enhancement of the Freund's incomplete adjuvant-induced writhing reaction by sodium ascorbate in mice.

We noticed that an intraperitoneal injection of Freund's incomplete adjuvant (FIA) into mice could stimulate the induction of a writhing reaction. The FIA emulsion-induced writhing reaction was found to be remarkably inhibited by preadministration of oral indomethacin, a non-steroidal anti-inflammatory and analgesic drug. The induction of the writhing reaction was also inhibited by intravenous preadministration of sodium ascorbate (SAs) in saline. In the experiments where SAs was added to FIA, it was demonstrated that SAs had dual activity of suppression and enhancement. At lower concentrations SAs functioned as a suppressor of the writhing reaction, while at concentrations higher than about 1 mg/50 microl/mouse it acted as an enhancer of the reaction. Furthermore, this writhing reaction induced by FIA+SAs emulsion was also inhibited by preadministraion of SAs itself as well as indomethacin. These results suggested that the mechanism of the writhing reaction induced by FIA was concerned with the production of prostaglandins (PGs), and SAs might be involved in regulation of the writhing reaction. In this paper, we propose a mouse writhing model induced by FIA or FIA+SAs emulsion as a novel pain model useful for assessment of analgesic and anti-inflammatory agents.

Analgesics↗
PubMed1999

Detection of anaphylactic reaction in the percutaneously sensitized mouse using the AW method.

Anaphylactic reactions of mice sensitized percutaneously with 2,4-dinitrofluorobenzene (DNFB) were investigated by the AW method assay, which is a mouse anaphylactic model using the abdominal wall as the site for induction with either 2,4-dinitrophenyl (DNP)-human serum albumin or anti-mouse IgE antibody and then estimation of the response. DNP-specific and IgE-dependent anaphylactic reaction after contact sensitization with DNFB could be induced and detected by the abdominal wall (AW) method assay in both groups with and without previous ear challenge with DNFB. Thus, the anaphylactic reaction in the group of twice-contact with 0.5% DNFB was observed on the 9th day from the sensitization (5th day from the ear challenge), and the reaction in the group of a single contact with 0.5% DNFB was observed 10 d after sensitization. The DNP-specific anaphylactic reaction was observed earlier than the 10th day with higher doses of DNFB. As for the mice of the former twice-contact group, the first and second characteristic ear swelling responses appeared within 1-6 h and 2 d of the ear challenge, respectively, and small swelling was observed 7 d after the challenge. It is suggested that Th1 and Th2 cells are activated at the almost same time, in other words, the preparation for both cell-mediated and humoral immunity could be accomplished to function, in vivo by a single percutaneous sensitization with DNFB.

Abdominal Muscles↗
PubMed1999

Glycyrrhizin inhibits TNF-induced, but not Fas-mediated, apoptosis in the human hepatoblastoma line HepG2.

To determine the transaminase-lowering action of glycyrrhizin (GL) immunologically, the effect of GL on tumor necrosis factor (TNF)-alpha- and Fas-mediated apoptosis was assessed using a human hepatoblastoma line, HepG2 cells. The HepG2 cells were resistant to TNF-alpha and anti-Fas antibody, but were rendered susceptible to TNF-alpha and anti-Fas antibody in the presence of actinomycin D (Act D), an inhibitor of RNA synthesis. The cytotoxicity induced by TNF-alpha/Act D or anti-Fas/Act D was accompanied by DNA fragmentation, indicating apoptotic death of HepG2 cells. GL partially prevented the apoptosis of HepG2 cells induced by TNF-alpha/Act D in a GL-dose dependent fashion. However, this protective effect of GL was not observed in the cytotoxicity of HepG2 caused by anti-Fas/Act D. Although the protection mechanism of GL, observed in a limited fashion against TNF-alpha-mediated apoptosis, is unclear, the present results provide an immunological explanation for the transaminase-lowering action of GL in the GL treatment of chronic liver diseases involving apoptotic hepatocyte death in their pathogenesis.

Anti-Infective Agents↗
PubMed1999

[Ligand recognition and activation mechanism of histamine H1 receptor].

Five amino acid residues of the human histamine H1 receptor that participate in histamine binding were identified using mutant H1 receptors by site-directed mutagenesis and 3D computer modeling of the receptor. The computer modeling provided two conformations of the receptor, non-active and active forms, and it was hypothesized that the binding of histamine to the receptor leads to the active state through the rewinding of the alpha-helix of TM-V. The binding sites of histamine were divided into two groups, one determined the ligand affinity and the other directly participated in the conformational change of the receptor, and the H1 antagonists bound only to the former. The mode of binding of histamine to the H1 receptor was different from those of catecholamine to the beta-receptor and of histamine to the H2 receptor.

Binding Sites↗
PubMed1999

[Identification of PKC isozymes and effect of knockdown of PKC alpha by antisense oligodeoxynucleotide on iNOS expression via interleukin-1 receptor in vascular smooth muscle cells].

Protein kinase C (PKC) family, is now classified into three groups; conventional (cPKC), novel (nPKC) and atypical (aPKC), and to date, 10 members of isozymes have been identified. We have suggested that PKC is essential to interleukin-1 (IL-1)-triggered expression of inducible NO synthase (iNOS), and that by pharmacological analysis, cPKC is not involved in iNOS induction in rat vascular smooth muscle cells (VSMC). In the present study, we identified some PKC isozymes and investigated the effect of PKC alpha knockdown by antisense oligodeoxynucleotide (AS-ODN) strategy on iNOS expression and nuclear translocation of NF-kappa B in RASMC. Western blot analysis revealed the presence of cPKC (alpha), nPKCs (delta and epsilon) and aPKCs (tau and lambda). Short-time (10-20 min) treatment with phorbol 12-myristate 13-acetate (PMA) induced translocation of PKC alpha from cytosolic to particulate fraction. PKC alpha was completely downregulated by treatment with 100 nM PMA for 24 hours. Treatment with AS-ODN against PKC alpha mRNA depleted PKC alpha specifically, and had no detectable effect on the other PKCs. The production of iNOS mRNA, but not nuclear translocation of NF-kappa B, stimulated by IL-1 beta was decreased by PKC alpha knockdown. These results suggest that there are 5 PKC isozymes in RASMC, and that PKC alpha is involved in iNOS expression triggered by IL-1 beta, supporting our previous pharmacological conclusion.

Animals↗
PubMed1999

Nystatin effects on vacuolar function in Saccharomyces cerevisiae.

The effects of nystatin, a polyene antibiotic, was studied in Saccharomyces cerevisiae by isolating and characterizing nystatin-sensitive mutants. We isolated a number of nystatin-sensitive mutants by ethylmethane sulfonate mutagenesis. One of these mutants, the nss1 mutant, was characterized in detail. The mutant was sensitive to stresses such as high temperature or high concentrations of monovalent and divalent cations. The nss1 mutants showed severe vacuolar protein sorting and vacuolar morphology defects. The nss1 mutant was demonstrated to have a mutational lesion in the known VPS16 gene, which is essential for vacuolar protein sorting in S. cerevisiae. All of the vacuolar deficient mutants (vps11, vps16, vps18, and vps33) were sensitive to nystatin. Nystatin was found to cause extensive enlargement of the vacuole in wild-type S. cerevisiae cells. These results are discussed with special reference to the vacuolar function of S. cerevisiae.

Alleles↗
PubMed1999

A novel mutation of the KAL1 gene in Kallmann syndrome.

Kallmann syndrome is defined by the association of hypogonadotropic hypogonadism and anosmia, for which three modes of transmission have been described: X-linked, autosomal recessive and autosomal dominant. The KAL1 gene, responsible for the X-linked form of the disease, has been isolated and its intron-exon organization determined. We report sequence analysis using PCR-direct sequencing method of the entire coding region and splice site junctions of the KAL1 gene in three males with Kallmann syndrome. We found a novel mutation in one case and no mutation in the other two cases. The mutation consisted of a C to T substitution in exon 1 converting codon 66 (CAG) encoding glutamine into a termination codon (TAG)/(Q66X). As a consequence of this mutation, the function of the KAL1 protein consisting of 680 amino acids was severely truncated so as to be consistent with Kallmann syndrome. As only this patient had unilateral renal hypoplasia among the three cases, this would suggest the existence of KAL1 gene mutation in this abnormality.

Adolescent↗
PubMed1999

In vivo gene transfer of a suicide gene under the transcriptional control of the carcinoembryonic antigen promoter results in bone marrow transduction but can avoid bone marrow suppression.

We constructed the CEA419/CD retrovirus vector carrying the cytosine deaminase (CD) gene directed by the carcinoembryonic antigen (CEA) promoter. pCD2 retrovirus vector carrying the CD gene directed by the retrovirus long terminal repeat promoter was also used. When mice bearing intraperitoneally disseminated colorectal carcinomas (CRCs) were infused intraperitoneally with pCD2 or CEA419/CD retrovirus-producing cells, a CD fragment was detected in CRCs and bone marrow cells. It was shown that the CD gene was expressed both in CRCs and in the bone marrow of animals infused with pCD2 retrovirus-producing cells, while the CD gene was expressed solely in CRCs of animals infused with CEA419/CD retrovirus-producing cells. These results indicate that the use of a tumor-selective promoter may warrant the safety of in vivo gene therapy using suicide genes.

Adenocarcinoma↗
PubMed1999

Electrochemotherapy against colorectal carcinoma: comparison of in vitro cytotoxicity of 5-fluorouracil, cisplatin and bleomycin.

Effectiveness of electrochemotherapy against colorectal carcinoma (CRC) was investigated in vitro using murine CRC cell lines. Electropermeabilization did not increase the sensitivity of CRC cells to 5-fluorouracil or cisplatin. Conversely, electropermeabilization markedly increased the sensitivity of CRC cells to bleomycin (BLM), resulting in 1,000-fold higher susceptibility. Subsequent analyses revealed that electropermeabilization significantly increased intracellular BLM levels of CRC cells. These results suggest that electrochemotherapy with BLM is a promising modality for the treatment of CRC, and that electrochemotherapy can be translated from the treatment of superficial tumors to the treatment of internal tumors including CRC.

Adenocarcinoma↗
PubMed1999

Identification of protein kinase C phosphorylation sites involved in phorbol ester-induced desensitization of the histamine H1 receptor.

The histamine H1 receptor (H1R)-mediated signaling cascade is inhibited by phorbol ester-induced protein kinase C (PKC) activation. Cloning studies of the H1Rs have shown that several potential PKC phosphorylation sites are located in the third intracellular loop of H1R. To elucidate the molecular mechanism of PKC-mediated desensitization, we identified amino acid residues that are involved in the desensitization of the H1R. Two amino acid residues (Ser396, Ser398) were determined to be PKC phosphorylation sites by in vitro phosphorylation studies using a series of synthetic peptides. Treatment with phorbol ester decreased histamine-induced accumulation of inositol phosphates in Chinese hamster ovary cells expressing the H1R with a rightward shift in the EC50 value, which implies the uncoupling of the receptor from the G protein. Site-directed mutagenesis studies showed that substitution of alanine for Ser398 but not for Ser396 markedly attenuated the effect of phorbol ester, which suggests that the Ser398 residue was primarily involved in PKC-mediated desensitization.

Amino Acid Sequence↗
PubMed1999

Semi-quantitative procedure for telomeric repeat amplification protocol (TRAP) assay in colorectal carcinomas.

Telomerase activity is intensively studied as a prognostic marker in malignancies, and generally detected by telomeric repeat amplification protocol (TRAP) assay. Recently, Ohyashiki et al. demonstrated a semi-quantitative procedure for TRAP assay, which is more useful than the qualitative one to analyze the correlation between telomerase activity and clinicopathological features in carcinomas. Therefore, we used semi-quantitative TRAP assay to analyze the correlation between telomerase activity and clinicopathological factors in colorectal carcinomas. Twenty-nine cases of advanced colorectal carcinoma, obtained by surgery, were studied. A telomerase detection kit, TRAP-eze, was used for the PCR based TRAP assay, and a DNA sequencer for a semi-quantitative analysis was used for a analysis. Telomerase activity was positively detected in all samples, and its mean value was 2.076+/-1.634 units (range; 0.536-8.932 units). Based on Dukes' classification, the activity tended to be higher in Dukes' A (2.722 units; P = 0.0525) and C (2.430 units) than in Dukes' B (1.552 units). The activity was higher in the right colon than at other locations. (right vs. left, rectum = 3.167 vs. 1.216 units; P<0.05, 1.604 units; P<0.01). The activity was higher in poorly differentiated adenocarcinoma than in well differentiated adenocarcinoma (3.743 vs. 1.491 units; P<0.05). Semi-quantitative TRAP assay is useful to analyze the correlation between telomerase activity and clinicopathological factors in colorectal carcinomas.

Aged↗
PubMed1999

[Anti-tumor effects of carmofur on human 5-FU resistant cells].

As a part of studies to clarify the efficacy mechanism of carmofur (HCFU), a 5-FU analog, the degree of cross-resistance to HCFU of cell lines of cultured human colon cancer DLD-1 and a stomach cancer NUGC-3, both of which had acquired resistance to 5-FU, was studied in vitro and in vivo. In vitro, both resistant cell lines showed no or little cross-resistance to HCFU under a short-term drug exposure, and very low cross-resistance to HCFU, as compared to resistance to 5-FU, under a long-term drug exposure. In therapeutic experiments using nude mice bearing parent or subcutaneously transplanted 5-FU-resistant DLD-1 cells, HCFU exerted almost the same growth-inhibitory effects on both tumors. These results suggest that HCFU itself may have its own anti-tumor mechanism, different from that of 5-FU.

Animals↗
PubMed1999

Antitumor effect of electrochemotherapy on colorectal carcinoma in an orthotopic mouse model.

Electropermeabilization was shown to markedly increase the sensitivity of murine colorectal carcinoma (CRC) cells to bleomycin (BLM), resulting in more than 2,500-fold higher susceptibility to BLM. Subsequent in vivo electrochemotherapy with BLM revealed profound antitumor effects on subcutaneous CRC tumors. Furthermore, when electrochemotherapy with BLM was employed for the treatment of orthotopic CRC tumors in mice, significantly prolonged survival priods were observed. These results indicate the feasibility of electrochemotherapy with BLM for the treatment of CRC and demonstrate that electrochemotherapy can be translated from the treatment of cutaneous and subcutaneous tumors to the treatment of internal cancers including CRC.

Animals↗