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Biomedical subjects

K Abe

Publications and source records attributed to K Abe.

At least 649 records · Page 36Linked to original sources
PubMed1999

[Combined chemotherapy with low-dose cisplatin, tegafur and uracil for head and neck squamous cell carcinomas].

The mechanism for the effect of cisplatin (CDDP) as a modulator for 5-fluorouracil (5-FU) has already been described. The effective AUC of serum 5-FU concentration with oral administration of tegafur and uracil (UFT) has been revealed. We administered a dose of 200-600 mg/body of UFT orally every day, and 3.5-10 mg/m2 of CDDP by drip infusion 5 days a week. Hospitalized patients were administered these agents for 2-5 weeks. Eleven patients were enrolled, including 4 with untreated pharyngeal squamous cell carcinoma (SCC), 5 with locoregional recurrent SCC, and 2 with pulmonary multiple metastases. The mean age of the patients was 71 years, and all patients had a PS 3. Of the 4 patients with untreated pharyngeal SCC, PR was noted in 3 and NC in one, for a response rate of 75%. Of the 11 patients with locoregional recurrent and pulmonary metastatic SCC, PR was noted in only one patient for a response rate of 14%. Although on average these patients died of the primary disease 150 days after chemotherapy, 4 patients later showed an improved PS stage, and could were able to leave the hospital. These 4 patients could stay home with a PS 0 or PS 1 for an average of 133 days, and survived with the disease for an average of 240 days after chemotherapy. No side effects were observed in any patients. In side of the low response rate for locoregional recurrent and pulmonary metastatic SCC, the present therapy was thought to be useful from the viewpoint of the quality of life.

Administration, Oral↗
PubMed1999

[Tetraprotomeric hypothesis of Na/K-ATPase].

Since the discovery of Na/K-ATPase by Skou, the mechanism of Na/K-dependent ATP hydrolysis and Na and K transport has been extensively studied. The hydrolysis appears to occur sequentially via the Na-Enzyme-ATP complex (NaE1ATP), ADP-sensitive phosphoenzyme (NaE1P), the K-sensitive phosphoenzyme (E2P) and the K-occluded enzyme (KE2), known the Post-Albers mechanism, in a protomer or diprotomer that consists of alpha- and beta-chains. The tetrameric nature of the enzyme such as a quarter, half, third to fourth and full site reactivity and the visualization by electron microscopy show direct biochemical evidence for the presence of a tetraprotomer structure of Na/K-ATPase during ATP hydrolysis. ATP binding is followed by two parallel paths, which occur at each of the two half sites for phosphorylation-dephosphorylation, and direct ATP hydrolysis via (NaE1P : E.ATP)2, (E2P : E.ATP : E2P : E.ADP/Pi) and (KE2 : E.ADP/Pi)2, respectively. The sequential formation of E2P from NaE1P and KE2 from E2P is accompanied by, respectively, hydrolysis of half of the TCA-labile bound ATP to ADP/Pi and of another half of the bound ATP to ADP/Pi. All reaction intermediates detectable in the Post-Albers scheme bind ATP and/or ADP/Pi.

Adenosine Diphosphate↗
PubMed1999

[Therapeutic efficacy of intra-peritoneal infusion of cisplatin and continuous intravenous infusion of 5-fluorouracil in gastric cancer patients with peritoneal metastasis].

A combination chemotherapy with intra-peritoneal infusion of CDDP and continuous intravenous infusion of 5-FU was used with a total of 16 gastric cancer patients with peritoneal metastasis (P 2 or P 3). Infuse A-port was inserted at the time of operation, CDDP 70 mg/m2 was administered intra-peritoneally at day 1, and 5-FU 700 mg/m2 was continuously administered intravenously at day 1-5. This treatment was repeated twice. Toxicity was evaluated according to the criteria from JCOG. Major toxicities of this regimen were anemia, leukocytopenia and nausea/vomiting. Except for one patient with Grade 3 venous thrombosis, all toxicities were less than Grade 2 and well tolerable. Median survival time was 343 days, but, one patient has survived more than 6 years. According to the multivariate analyses, depth of invasion was selected as an independent prognostic factor for this treatment. This therapy is considered to be a safe and effective treatment modality for gastric cancer patients with peritoneal metastasis.

Adult↗
PubMed1999

[Application of measuring 99mTc-MAG3 plasma clearance based on one-compartment model (MPC method) to renal transplantation].

Measurement of 99mTc-MAG3 plasma clearance (CLmag) based on one-compartment model (MPC method) was applied to renal transplantation and evaluated for the factors which might affect the calculated results, especially concerning renal depth. Correlation coefficient of CLmag between MPC method using real renal depth and Russell or Bubeck single sampling method was good (r = 0.852 or 0.876, respectively). Regression equation between MPC method and Russell method was y = 1.044x - 3.0 and was more closer to y = x than that between MPC method and Bubeck method. CLmag of MPC method calculated by estimated renal depth from the abdominal thickness was also similar to that by real renal depth. Even if the fixed renal depth, 4 cm, was applied, the coefficient and regression equation between MPC method and Russell method were r = 0.884 and y = 1.004x - 10.2. In conclusion, MPC method is applicable to the evaluation of renal transplants. Though measuring renal depth is best, calculation with fixed renal depth of 4 cm might be practically acceptable.

Adult↗
PubMed1999

[Eosinophilic pneumonia without eosinophilia in BALF or peripheral blood and diagnosed by open lung biopsy].

A 47-year-old woman was referred to our hospital because of cough and an abnormal shadow in the left lung field. The infiltrate reduced without therapy and another infiltrate appeared in the right lung field. Bronchiolitis obliterans organizing pneumonia was clinically suspected due to the absence of signs of eosinophilia in peripheral blood and bronchoalveolar lavage fluid (BALF). Open lung biopsy specimens disclosed alveolitis with mononuclear cell infiltration and organization within the air spaces of bronchioli and alveolar ducts. The observation of pronounced eosinophil infiltration in the alveolar spaces of some specimens yielded a diagnosis of eosinophilic pneumonia. After steroid therapy, the abnormal shadows disappeared. BALF lymphocyte surface marker analysis detected no decrease in the CD4/CD8 ratio; activated CD4 and CD8 lymphocytes were notably higher than the corresponding levels in peripheral blood. IL-5, IL-3, and GM-CSF values in BALF were not significantly elevated. This was a case of borderline eosinophilic pneumonia that was difficult to diagnose on the basis of clinical parameters alone.

Anti-Inflammatory Agents↗
PubMed1999

[Missense mutations of the butyrylcholinesterase gene in six Japanese patients with low cholinesterasemia: genetic analysis using sera stored in a freezer].

Six serum samples with no detectable butyrylcholinesterase (BCHE) activity had been stored at -70 degrees C for more than 10 years. These sera were used for amplification of BCHE gene using polymerase chain reaction (PCR) and for nucleotide sequence analysis. Five of them demonstrated a C-->T transition at codon 100 (CCA-->TCA), resulting in a Pro-->Ser substitution. The other one was a compound heterozygote as revealed a T-->C transition mutation at codon 203 from TCA (Ser) to CCA (Pro) and G-->C transversion at codon 365 from GGA (Gly) to CGA (Arg). These results showed sera stored in a freezer could be used as a starting material for amplification of genomic DNA when it is not possible to obtain fresh blood samples.

Asian People↗
PubMed1999

Phylogenic analysis of echovirus type 30 isolated from a large epidemic of aseptic meningitis in Japan during 1997-1998.

During 1997 to 1998, a nationwide epidemic of aseptic meningitis occurred in Japan. More than 4,500 isolates from patients with aseptic meningitis were identified as echovirus type 30. To investigate the character of these isolates, we examined the nucleotide sequences of thirty-seven geographical representatives and compared them with 50 strains isolated during the past 20 years. The phylogenic analysis used partial sequences from either the VP1 or VP4-VP2 region of the viral capsid. This analysis revealed that the isolates were divided into six genomic groups. All isolates identified during 1997-1998 belonged to only two genomic groups; these two groups are thought to be the causative viral agents involved in the recent epidemic.

Enterovirus B, Human↗
PubMed1999

[Successful treatment with splenic irradiation for idiopathic thrombocytopenic purpura associated with primary immunodeficiency syndrome].

A 50-year-old man was admitted to our hospital because of intracranial hemorrhage and thrombocytopenia (platelet count: 3,000/microliter). Low levels of IgG (76 mg/dl) and IgA (30 mg/dl) and a normal pattern of peripheral blood T and B cell subsets yielded a diagnosis of common variable immunodeficiency (CVID). The number of megakaryocytes in bone marrow was within normal limits (64/microliter), and a diagnosis of idiopathic thrombocytopenic purpura was made. Both high-dose intravenous gamma-globulin and prednisolone were ineffective. Because of the coexistence of CVID, splenic irradiation (total 15 Gy) was performed instead of splenectomy. The platelet number began to increase 5 days after the initiation of irradiation, had increased to 8.7 x 10(4)/microliter at the end of irradiation, and was 22.9 x 10(4)/microliter 2 weeks later.

Common Variable Immunodeficiency↗
PubMed1998

Molecular cloning and taste bud-specific expression of a novel cyclic nucleotide-gated channel.

Cyclic nucleotide-gated (CNG) channels serve as downstream targets of signaling pathways in vertebrate photoreceptor cells and olfactory sensory neurons. For taste signaling as well, a great deal of information is available predicting the presence of a CNG channel, but no report has been presented on its molecular entity. Here we report on molecular cloning and functional expression of a taste bud-specific CNG channel tentatively named CNGgust. Reverse transcriptase polymerase chain reaction (RT-PCR) primers were synthesized according to some amino acid sequences generally conserved in many CNG channels. RT-PCR was conducted using rat circumvallate papillary mRNA-derived cDNA as a template to obtain positive clones. A corresponding genomic DNA clone was then obtained by screening from a genomic DNA library. Dissecting the entire structure of this gene, we found that the encoding protein had an amino acid sequence similarity of 80% to each of retina and olfactory CNG channels. It was also found by immunostaining with a specific antibody that this gustatory CNG channel (CNGgust) is localized in the tongue and also expressed specifically on the pore side of each taste bud in the circumvallate papillae. Electrophysiological experiments demonstrated that CNGgust resided in a functional state. All these data suggest that CNGgust may be involved in taste signal transduction in sensory cells.

Amino Acid Sequence↗
PubMed1998

Apolipoprotein E regulatory region genotype in schizophrenia.

Clinical observations indicate that a proportion of patients with schizophrenia experience cognitive impairment, which suggests that a neurodegenerative basis might be involved in the etiology of schizophrenia. Apolipoprotein E (ApoE), which has been confirmed to be genetically associated with Alzheimer's disease, is thus highlighted as a candidate gene for schizophrenia. Recently, novel functional polymorphisms in the ApoE transcriptional regulatory region have been found. To investigate whether these polymorphisms are associated with the risk of schizophrenia, we genotyped 144 patients with schizophrenia and 134 controls for two polymorphisms (-491A/T and -219G/T). No significant positive associations between both polymorphisms and schizophrenia were observed. Our findings exclude the regulatory region of the ApoE gene as a locus that might confer increased susceptibility to schizophrenia.

Apolipoproteins E↗
PubMed1998

Overexpression of AML1 renders a T hybridoma resistant to T cell receptor-mediated apoptosis.

The AML1 gene, which encodes the DNA binding subunit of the heterodimeric transcription factor, PEBP2/CBF, is involved in several types of chromosomal translocations associated with human acute myeloid leukemia, and has been shown by gene targeting to be essential for the development of definitive hematopoiesis in the murine fetal liver. In addition, the gene is expressed abundantly in T lymphocytes and has been implicated in T cell specific gene expression. In the present study we examined the function of AML1 in T cell receptor (TCR)-mediated, Fas/Fas-ligand dependent apoptosis of a T hybridoma line, DO11.10. Several independent cell clones overexpressing the AML1 protein were isolated by transfecting AML1 cDNA into these cells. These clones possessed an increased level of PEBP2/CBF DNA binding activity and were found to be resistant to apoptosis induced by anti-CD3 antibody treatment. Northern blot analysis revealed that induction of the Fas-ligand transcript was markedly suppressed in the anti-CD3 treated clones. Instead, expression of IL-2 receptor alpha subunit (IL-2R alpha), which is a manifestation of proliferative TCR signaling, was induced. This was in contrast to the parental, anti-CD3 treated DO11.10 cells where induction of Fas-ligand but not of IL-2R alpha was observed. Resistance of the AML1 overexpressing cell clones to TCR-mediated apoptosis is most likely attributable to the lack of Fas-ligand induction, since simultaneous treatment with anti-CD3 and anti-Fas antibodies caused apoptosis of the clones. The overall results suggest that the AML1 protein may play a pivotal role in switching TCR signaling between apoptosis and cell proliferation in T lymphocytes.

Animals↗
PubMed1998

Induction of DNA fragmentation and HSP72 immunoreactivity by adenovirus-mediated gene transfer in normal gerbil hippocampus and ventricle.

Foreign genes have been successfully transferred and expressed in experimental animal brains using adenoviral vectors. However, it is not fully understood whether adenovirus-mediated gene transfer causes stressful or cytotoxic injury in brain. A replication-defective adenoviral vector containing the Escherichia coli lacZ gene (AdCMVnLacZ) was directly injected into right hippocampus and lateral ventricle of normal gerbil brains. Temporal and spatial profiles of the expression of lacZ gene products, DNA fragmentation detected by terminal deoxynucleotidyl d-UTP nick end labeling (TUNEL) staining, and heat shock protein 72 (HSP72) immunoreactivity were examined until 21 days after the injection. In the ventricle, lacZ gene was immediately and strongly expressed at 8 hr after the injection of AdCMVnLacZ, with a peak at 1-3 days, and disappeared by 21 days. Although a small number of choroid plexus cells were TUNEL positive at 3 and 7 days, no HSP72 immunostaining was observed in the ventricle. Small-to-moderate expression of lacZ gene was found in the needle route from 8 hr to 3 days after the injection, and a small number of TUNEL-positive cells were detected at the needle track at 1-3 days. In the hippocampus, lacZ gene was markedly expressed around the dentate gyrus (DG) at 8 hr to 3 days with a peak at 1 day. Large number of TUNEL or moderate-to-dense HSP70 staining cells were also detected in the same area. CA1 neuronal cells just adjacent to the needle route showed TUNEL positivity at 1 to 3 days. However, the TUNEL staining was not associated with lacZ gene expression. The majority of lacZ-expressing cells were discriminated from the TUNEL-positive cells, whereas some were double-positive with HSP72 staining in DG. Cellular loss was observed in the CA1 layer around the needle route. An apoptotic change was morphologically observed in the marginal region of the DG at 1-3 days and in the ventricle at 3-7 days. In the sham control group, TUNEL-positive or HSP72-staining cells were only detected around the needle track including CA1 cells adjacent to the needle route. These data suggest that adenoviral gene transfer may induce direct traumatic injury in the CA1 sector near the needle route, indirect apoptotic cell loss in the DG and ventricle, and stressful effect on the dentate granule cells in association with adenovirus infection in normal gerbil brain.

Adenoviridae↗
PubMed1998

Cyclic GMP-dependent but G-kinase-independent inhibition of Ca2+-dependent Cl- currents by NO donors in cat tracheal smooth muscle.

1. The effects of NO donors on Ca2+-dependent Cl- currents (ICl(Ca)) were investigated in freshly isolated cat tracheal myocytes using the whole-cell patch clamp technique. 2. With nystatin-perforated whole-cell recording, carbachol (CCh, >/= 1 microM) induced a transient inward current (ICCh) with a reversal potential of about -20 mV. Activation of ICCh probably occurred through the M3 muscarinic receptor, since nanomolar concentrations of 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) greatly inhibited this current, while 11-(2-(diethylamino)methyl)-1-piperidinylacetyl)-5, 11-dihydro-6H-pyrido (2,3beta) (1,4)benzodiazepine-6-one (AF-DX 116) or pirenzepine at concentrations of up to 1 microM were almost ineffective. 3. Chloride channel/transporter blockers such as DIDS (100 microM), anthracene-9-carboxylic acid (9-AC, 100 microM) and niflumic acid (100 microM) greatly inhibited ICCh, but cation channel blockers, such as nifedipine (10 microM), Zn2+ (500 microM) or Gd3+ (500 microM), were without effect. 4. Activation of ICCh was strongly attenuated by pretreatment with ryanodine (4 microM) plus caffeine (10 mM). Addition of neomycin (1 mM) into the bath or inclusion of heparin (3 mg ml-1) in the pipette abolished a substantial part of ICCh. These results suggest that ICCh is ICl(Ca), which is activated by inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release. 5. The nitric oxide donor S-nitroso-N-acetyl penicillamine (SNAP) reduced the amplitude of ICCh dose dependently (IC50, approximately 10 microM). Similar inhibition was also exerted by other types of NO donor such as glyceryl trinitrate (GTN) and (+/-)-E-methyl-2-(E-hydroxyimitol)-5-nitro-6-methoxy-3- hexeneamide (NO-R). 6. SNAP-induced ICCh inhibition was effectively antagonized by Methylene Blue (1-100 nM), and mimicked by dibutyryl cGMP (db-cGMP) (0.5-1 mM), whereas two structurally distinct types of cGMP-dependent (G)-kinase inhibitor, N-(2-aminoethyl)-5-isoquinilinesulphonamide (H-8, 2.5 microM) and KT5823 (1 microM), failed to counteract the inhibitory effects of SNAP or db-cGMP. Another G-kinase-specific inhibitor Rp-8-(para-chlorophenylthio)guanosine-3',5'-cyclic monophosphorothioate (Rp-8-pCPT-cGMPS; 1 microM) itself caused a marked reduction in ICCh. 7. SNAP (100 microM) or db-cGMP (100 microM) exhibited no inhibitory actions, when caffeine (10 mM) or photolytically released IP3 were used instead of CCh to activate the inward current. 8. These results suggest that inhibition of ICCh by NO donors involves a cGMP-dependent but G-kinase-independent mechanism, which may operate at a site(s) between the muscarinic (M3) and IP3 receptors.

Animals↗
PubMed1998

Biologically active oligodeoxyribonucleotides. 5. 5'-End-substituted d(TGGGAG) possesses anti-human immunodeficiency virus type 1 activity by forming a G-quadruplex structure.

A series of hexadeoxyribonucleotides (6-mers), d(TGGGAG), substituted with a variety of aromatic groups at the 5'-end were synthesized and tested for anti-human immunodeficiency virus type 1 (HIV-1) activity. While unmodified d(TGGGAG) (31) had no anti-HIV-1 activity, compound 23 with a 3,4-di(benzyloxy)benzyl (DBB) group at the 5'-end potently inhibited the HIV-1IIIB-induced cytopathicity of MT-4 cells in vitro (IC50 = 0.37 microM) without cytotoxicity up to 40 microM. A thermal denaturation study on the 5'-end-substituted 6-mers by means of the circular dichroism (CD) spectra demonstrated that the aromatic substituent attached at the 5'-end of the 6-mer strongly enhanced the formation of a parallel helical structure consisting of four strands (quadruplex). On the contrary, compound 36, in which one of the guanosines of 23 was replaced by a thymidine, did not form a quadruplex, thus exhibiting no anti-HIV-1 activity. Moreover, both compound 15, with a tert-butyldiphenylsilyl group solely at its 3'-end, and compound 21, with a relatively small substituent, a benzyl group, at the 5'-end, formed quadruplexes but had no anti-HIV-1 activity. These findings led us to the conclusion that both the quadruplex structure and the aromatic substituent with adequate size at the 5'-end are crucial for the interaction of the 5'-end-substituted 6-mers with the V3 loop as well as the CD4 binding site on viral gp120, resulting in anti-HIV-1 activity.

Anti-HIV Agents↗