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Biomedical subjects

K Taniguchi

Publications and source records attributed to K Taniguchi.

At least 523 records · Page 29Linked to original sources

Relation between myocardial beta-adrenergic receptor and left ventricular function in patients with left ventricular volume overload due to chronic mitral regurgitation with or without aortic regurgitation.

The relation between myocardial beta-adrenergic receptor and left ventricular (LV) function was studied in 10 patients, aged 41 to 61 years (average 51), with LV volume overload mainly due to chronic mitral regurgitation. Beta-adrenergic receptors were examined using crude membrane in LV papillary muscle obtained at mitral valve replacement. Cardiac function was evaluated at preoperative cardiac catheterization with the interval to surgery of 1 to 33 months (average 7). Beta-adrenergic receptor density in 7 patients with New York Heart Association class II or III congestive heart failure was higher than that in 3 patients with class IV heart failure (59 +/- 19 vs 37 +/- 3 fmol/mg protein, p less than 0.05). Beta-adrenergic receptor density showed a positive correlation with end-systolic stress/end-systolic volume index ratio, the index for contractile function (p less than 0.005). Other parameters such as cardiac index, pulmonary artery wedge pressure and LV ejection fraction had no significant correlation to beta-adrenergic receptor. The results demonstrated that increases in symptom and LV dysfunction, particularly of the contractile state, was associated with decreased myocardial beta-adrenergic receptor density from possible down-regulation in patients with chronic mitral regurgitation with or without aortic regurgitation.

Adult↗

Operational overlapping of cross-reactive and serotype-specific neutralization epitopes on VP7 of human rotavirus serotype 3.

VP7-specific neutralizing monoclonal antibodies (N-MAbs) to serotype 3 human rotavirus were produced to analyze serotype 3-specific and cross-reactive neutralization epitopes on VP7. On the basis of the reactivity patterns in neutralization tests with various human and animal strains, a total of 10 N-MAbs could be classified into four groups; five antibodies specific to serotype 3 were divided into two groups, and five antibodies consisted of two groups which are cross-reactive with strain 69 M (serotype 8) or strain WI61 (serotype 9). Seven N-MAbs showed the same reactivity patterns to the virus strains in both neutralization tests and enzyme-linked immunosorbent assay (ELISA), while three N-MAbs specific to serotype 3 in neutralization showed a cross-reactivity with the serotype 8 strain in ELISA. Neutralization-resistant mutants of serotype 3 strains P and YO were selected by the N-MAbs. Cross-neutralization tests between the mutants and the MAbs indicated the presence of two serotype-specific (S1 and S2) and three cross-reactive (C1, C2, and C3) epitope groups. S1, S2, and C3 epitope groups overlapped operationally each other, and the S1 epitope group had an overlapping with the C1 epitope group. However, C2 epitope group identified by the MAbs which neutralized serotypes 3 and 9, had no operational overlapping with any other epitope groups.

Animals↗

Preparation and characterization of a neutralizing monoclonal antibody directed to VP4 of rotavirus strain K8 which has unique VP4 neutralization epitopes.

For selecting the neutralizing monoclonal antibodies (N-MAbs) directed to VP4 of rotavirus strain K8, which has unique VP4 neutralization epitopes, we prepared several reassortant viruses by mixed infection of two different strains K8 (serotype 1) and P (serotype 3) in vitro: three reassortant clones having VP4 of K8 and VP7 of P and four clones having VP4 of P and VP7 of K8. By using these reassortants in screening hybridomas, a N-MAb (K8-2C12) directed to strain K8-specific VP4 was obtained. The MAb K8-2C12 neutralized only K8 when tested against numerous strains of different serotypes, while in enzyme-linked immunosorbent assay this MAb reacted also with simian rotavirus SA11 (serotype 3), bovine rotavirus NCDV (serotype 6), and human rotavirus (HRV) strain 69M (serotype 8). Neutralization-resistant mutants of K8 were selected by the K8-2C12 antibody and VP4 amino acid sequences of the mutants were determined. Single amino acid substitution was detected in the three mutant clones at position 394, which is included in the major cross-reactive neutralization region identified in other rotaviruses.

Amino Acid Sequence↗

Membrane transport of 1-beta-D-arabinofuranosylcytosine and accumulation of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate in P388 murine leukemic cells resistant to vincristine.

The membrane transport of ara-C and intracellular ara-CTP accumulation were investigated in P388 murine leukemic cells resistant to vincristine (P388/VCR) and its parent cell line. The transport of ara-C in P388/VCR cell line was a 1.4-fold increase at 30 sec compared to that in P388 parent cell line (P less than 0.01). The increase of the transport of ara-C in P388/VCR cell line, however, was not completely abolished by the nucleoside transport inhibitor, nitrobenzylthioinosine (NBTI) to the level in parent cell line. Scatchard analyses revealed that the resistant cells had significantly less NBTI binding sites than the parent cells had. These results suggested that the changes in ara-C transport in P388/VCR cells were due, in part, to increase of NBTI-insensitive transport sites in the membrane. The measurement of the intracellular ara-CTP concentration by high-performance liquid chromatography revealed that the intracellular ara-CTP level in P388/VCR cells was also significantly higher than that in parent cells (1.4-fold, P less than 0.01). As the transport of ara-C is rate limiting at a concentration of 1 microM in the both cell lines, we concluded that the accumulation of ara-CTP in P388/VCR cells might have partially resulted from the enhancement of the ara-C transport.

Animals↗

Alteration in natural defense activity against NK-susceptible B16 melanoma cells after treatment with Corynebacterium parvum.

We have investigated the effects of administration of C. parvum on host anti-metastatic activity against B16 melanoma H-2L, a natural killer (NK) sensitive clone with a low expression of H-2b. The anti-metastatic activity was estimated by monitoring the following two points. One was the survival ratio at an early stage after an intravenous (iv) inoculation of radiolabeled B16 H-2L cells, the other was the formation of pulmonary metastases after iv injection with the tumor cells. Administration of C. parvum showed a biphasic change in the NK activity of the spleen cells and the peritoneal exudate cells (PEC) in mice. At an early phase (2-3 days) after administration of C. parvum, the NK activity of the spleen cells and PEC was significantly augmented. On the other hand, at a later phase (14 days) after C. parvum administration, the NK activity was deeply depressed. In correlation with NK activity of the mice treated with C. parvum, the anti-metastatic activity of the hosts was augmented in the early phase, whereas a depressed level of anti-metastatic activity was observed in the late phase after administration of C. parvum. These results suggest that the modification of NK activity is a possible basis for modulation of anti-metastatic activity by C. parvum.

Animals↗

Differential growth inhibition of isoquinolinesulfonamides H-8 and H-7 towards multidrug-resistant P388 murine leukaemia cells.

The effects of N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8) and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) on the growth of P388 and its multidrug-resistant (MDR) variants were examined with the objective of assessing the possible changes in cyclic nucleotide-dependent protein kinases and protein kinase C-mediated pathways associated with MDR. H-8, an inhibitor of cyclic nucleotide-dependent protein kinases, inhibited the growth of the parental P388 murine leukaemic cells, but not that of MDR variants up to 200 microM. However the growth of both drug-sensitive and resistant cell lines were uniformly inhibited by H-7. Both the cytotoxic and cytokinetic results revealed that the growth-inhibition by H-8 of P388 cells is mainly due to a blockade of cell-cycle progression rather than due to a killing of cells. The degree of resistance to H-8 was directly proportional to their extent of resistance to vincristine, adriamycin, and 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene)-beta-D-gluco pyr anoside (VP-16) and to that of the expression of P-glycoprotein. These findings raised the possibility that P-glycoprotein might play a role in the cross-resistance to H-8. To test the hypothesis, we examined the effect of H-8 on the binding of 3H-vincristine to membrane fraction isolated from P388/VCR-600 cells and on the enhancement of cytotoxicity to anticancer drugs in MDR cells. H-8 did not have any influences on these reactions. Thus, the cross-resistance to H-8 may be mediated through a mechanism different from an overexpression of P-glycoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Analysis of the newly identified neutralization epitopes on VP7 of human rotavirus serotype 1.

Neutralizing monoclonal antibodies (MAbs) directed to the VP7 protein and neutralization-resistant mutants were used to analyse the antigenic structure of VP7 of human rotavirus serotype 1. Cross-neutralization tests using the MAbs and the resistant mutants indicated the existence of two functionally independent neutralization epitope regions (S1 and S2) on VP7. Region S1 corresponds to a single epitope domain of VP7 which has been detected previously. Two MAbs prepared in this study recognized the S1 region, and the resistant mutants they selected had amino acid substitutions at positions 94 or 213. On the other hand, region S2 is considered to be a novel epitope. Single or double amino acid substitutions were detected in the variable regions (amino acid positions 145, 217 and 221) and in the constant regions (positions 104, 201 and 291) of the VP7 protein of mutants selected by MAbs directed to the S2 region. It was suggested that the variable region E (amino acids 208 to 221) includes two independent neutralization sites, and that amino acid substitutions in the constant region of VP7 also affect serotype-specific neutralization epitopes. Neutralization epitopes on VP7 are considered to be highly dependent on the conformation of VP7.

Animals↗

Molecular and antigenic analyses of serotypes 8 and 10 of bovine rotaviruses in Thailand.

Antigenic and genomic properties of non-serotype 6 bovine rotaviruses isolated in Thailand and Japan were studied by cross-neutralization tests, nucleotide sequence determination of the VP7 gene, and RNA-RNA hybridization. Two Thai strains (61A and A44) were serologically related to a Japanese isolate KK3 which has been assigned to serotype 10. In contrast, strain A5 was found to be antigenically similar to human strain 69M with serotype 8 specificity, although strain A5 showed a one-way cross-reaction with serotype 6 strain NCDV. VP7 sequence analysis confirmed these results. High degrees of similarity in nucleotide and amino acid sequences (92.5 to 98.2% and 96.3 to 97.9%, respectively) were found among the VP7 genes of the four serotype 10 bovine strains (61A, A44, KK3 and B223). The VP7 amino acid sequence of strain A5 was similar to those of serotype 8 human strains (91.7% and 94.8% for strains B37 and 69M, respectively). In RNA-RNA hybridization experiments, a high level of overall relatedness was found among the three serotype 10 bovine strains (61A, A44 and KK3), and strains A5 and NCDV were also moderately related to the three serotype 10 viruses. All the bovine rotaviruses tested in this study, regardless of their serotype specificity, exhibited a moderate genetic-relatedness to strain 69M of serotype 8, and, to a lesser extent, to serotype 2 human rotavirus strains.

Amino Acid Sequence↗

Analysis of the neutralization epitopes on human rotavirus VP7 recognized by monotype-specific monoclonal antibodies.

Three anti-VP7 monoclonal antibodies (MAbs) which neutralized only two strains (K8 and S12) of five serotype 1 human rotaviruses (HRVs) were obtained, and neutralization epitopes recognized by these 'monotype-specific' MAbs were analysed by epitope mapping and sequencing of the VP7 genes. Neutralization-resistant mutants of K8 and S12 were selected by the monotype-specific MAbs and serotype 1-specific MAbs prepared previously. Cross-neutralization tests between MAbs and neutralization-resistant mutants of K8 and S12 indicated that epitopes of monotype-specific MAbs operationally overlap with those of serotype 1-specific and cross-reactive MAbs recognizing the S1 region. Sequence analyses of the VP7 genes indicated that VP7s of strains K8 and S12, which belong to a monotype of serotype 1 viruses, possessed amino acids at positions 42 and 87 different from other serotype 1 HRVs. Furthermore, amino acid substitution sites of representative mutants of K8, selected by the monotype-specific MAbs, were identified at positions 96, 97 and 100. These results imply that amino acids in variable region B (amino acids 87 to 101) are involved in the monotype-specific neutralization epitope as well as serotype-specific neutralization epitopes.

Amino Acid Sequence↗

Analysis of human rotavirus strains prevailing in Bangladesh in relation to nationwide floods brought by the 1988 monsoon.

The virologic character of human rotavirus strains prevailing in Bangladesh was investigated in relation to the devastating nationwide floods brought by the 1988 monsoon. Human rotaviruses contained in stool specimens that were collected from inpatients with infantile and adult diarrhea in two hospitals in Mymensingh over a 13-month period (January 1988 to January 1989) and in one hospital in Dhaka over a 3-month period (February to April 1988) were examined for their subgroup, VP7 serotype, and RNA electropherotype. In concurrence with the spread of the flood (from the middle of August 1988), the number of infantile and adult diarrhea patients increased greatly. At the same time, the proportion of rotavirus-positive specimens in all diarrhea cases also increased remarkably, reaching 54 and 45% in September and October, respectively. An electrophoretic analysis of viral RNA revealed 17 distinct patterns of viral RNA (14 long and 3 short electropherotypes) and a considerable number of mixed electropherotypes, suggesting the simultaneous infection of some patients with more than two rotavirus strains. It was noteworthy that electropherotypes of rotavirus strains prevailing in the community changed considerably after the spreading of the flood and that the frequency of virus specimens showing mixed electropherotypes increased significantly during the flood period. These results suggest that sudden environmental change caused by the devastating floods seriously affected the epidemiology of rotavirus infections by increasing the opportunity of transmission of the virus and by reducing the resistance of the host to infection. In both pediatric and adult patient groups, serotypes 1 and 2 were the most frequent ones detected, followed by serotype 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Antibody response to serotype-specific and cross-reactive neutralization epitopes on VP4 and VP7 after rotavirus infection or vaccination.

By using a competitive solid-phase immunoassay with serotype-specific and cross-reactive neutralizing monoclonal antibodies directed at VP4 and VP7, we tested the antibody responses to some neutralization epitopes on VP4 and VP7 in individuals infected or vaccinated with rotavirus. Antibody responses to VP7 epitopes of the infecting serotype of virus were found at a high frequency in both infants and children. In contrast, antibody responses to VP4 and heterotypic VP7 were observed only when the individuals possessed antibodies to any serotype of rotavirus in their acute-phase or prevaccination sera.

Antibodies, Viral↗

Development of bacillus Calmette-Guérin-induced antitumor activity in peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMNCs) after bladder instillation of bacillus Calmette-Guérin (BCG) to patients with superficial bladder carcinoma showed lytic activity against natural killer (NK)-sensitive and NK-resistant target tumor cells. PBMNCs in normal volunteers were isolated and cultured with BCG (5 micrograms/ml) in vitro. Maximum cytotoxicity was obtained within 24 h. Cytosine arabinoside as a DNA synthesis inhibitor did not inhibit this killer cell activation. Monoclonal antibody treatment revealed that both precursor and effector cells were NK cell type. However, effector cells had a wider spectrum of target cells than usual NK cells. The recognition specificity from cold target competition experiments was selective.

Administration, Intravesical↗

Endothelin-1 induces hypertrophy with enhanced expression of muscle-specific genes in cultured neonatal rat cardiomyocytes.

To determine whether endothelin-1 (ET-1) induces hypertrophy of cardiomyocytes, the effects of ET-1 on the expression of muscle-specific genes and a proto-oncogene, c-fos, in cultured neonatal rat cardiomyocytes were examined by Northern blot analysis. ET-1 (10(-7) M) induced about twofold to fourfold increases in the gene expression of myosin light chain 2, alpha-actin, and troponin I after 6 hours, which continued up to 24 hours. The ET-1-induced increases in mRNA levels for these muscle-specific genes were dose dependent (10(-9) to 10(-7) M). Run-on transcriptional assay showed that the changes in mRNA level for three muscle-specific genes were regulated, at least in part, at the transcriptional level. 12-O-Tetradecanoylphorbol 13-acetate (TPA), a potent protein kinase C activator, and the Ca2+ ionophore ionomycin also increased mRNA levels of three muscle-specific genes. ET-1, TPA, and ionomycin similarly induced the expression of c-fos after 30 minutes, which returned to an undetectable level after 6 hours. ET-1 remarkably and dose-dependently stimulated accumulation of total inositol phosphates in cardiomyocytes. Morphometrical evaluation showed that ET-1 significantly increased surface area of cardiomyocytes without cell proliferation. ET-1 also dose-dependently stimulated the synthesis of protein and DNA, which was unaffected by the L-type calcium channel blocker nicardipine. These data suggest that ET-1 induces hypertrophy of cardiomyocytes associated with the induction of muscle-specific gene transcripts through the possible involvement of protein kinase C activation or intracellular Ca2+ mobilization.

Animals↗

Effects of beta-adrenergic agonists on metabolic activations of human neutrophils.

Although effects of adrenergic agonists on metabolic activation of neutrophils have been studied for over a decade, amounts of released arachidonic acid and its metabolites from the cells activated by chemotactic peptide (FMLP) are so small that the results have been in conflict. In this study, we developed a method to obtain enough amount of arachidonic acid released to examine the action sites of adrenergic agonists with respects to the metabolic bursts of human neutrophils. First, superoxide generation from the cells was estimated and the results indicated that the adrenergic agonists, such as isoproterenol, salbutamol, procaterol and epinephrine, inhibited over 70% and 40% of the superoxide generation stimulated by FMLP and serum treated zymosan (STZ), respectively. Another metabolic activation, the release of arachidonic acid, was achieved by FMLP if the cells were incubated with merthiolate (20-80 microM), but the merthiolate-treatment was ineffective on the cells activated by calcium ionophore (A23187). Isoproterenol and epinephrine decreased the arachidonic acid release only when the cells were activated by FMLP in the presence of merthiolate. In spite of the fact that isoproterenol (1 and 10 microM) hardly inhibited the arachidonic acid release activated by A23187, formations of leukotrienes were decreased up to approximately 70% of control level. Intracellular calcium concentration elevated by FMLP was hardly diminished by isoproterenol and salbutamol. From these observations, it appears likely that adrenergic agonists attenuate the signal transmission process of FMLP at a post-receptor site of action at a step before the activation of protein kinase C or phospholipase A2.

Adrenergic beta-Agonists↗

Inhibitory effects of histamine H1 receptor blocking drugs on metabolic activations of neutrophils.

Inhibitory effects of various histamine receptor-blocking agents including antiallergic agents on metabolic activations of neutrophils were examined by measuring leukotrienes (C4, D4 and E4) formation, arachidonic acid release and superoxide generation. The stimulation of neutrophils by calcium ionophore (A23187) causes the production of leukotrienes concomitantly with the release of arachidonic acid from the cells and these were effectively diminished with a variety of antihistaminic agents. Almost all the histamine H1 receptor-blocking drugs studied here showed as inhibitors of the metabolic activations of neutrophils, although the degree was dependent on the drug concentrations. The order of potency of the inhibitory effects on the arachidonic acid release were: homochlorcyclizine, clemastine, and azelastine (IC50 less than 20 microM) greater than oxatomide (IC50 less than 60 microM) and diphenylpyraline greater than triprolidine, meclizine, diphenhydramine (IC50 greater than 100 microM). The superoxide generation from neutrophils activated by phorbol 12-myristate 13-acetate was also effectively inhibited by these agents, but generally lower concentrations were required to obtain the same degrees of effects. These results indicated that some of the histamine H1 receptor-blocking drugs, such as clemastine and homochlorcyclizine, may act as inhibitors of formation of leukotrienes at the locus of inflammation.

Arachidonic Acid↗

[Imaging analysis of antiulcer action and the active constituent of Atractylodis rhizoma].

Examination of the sizes of gastric mucosal injury has been conducted by visual means. However, the human visual-eye examination may sometimes involve personal biases and errors. In order to reduce these errors, automated analytical apparatuses have been developed. The equipment is generally expensive. In the present study, a low-cost imaging analytical method to examine the antiulcer action of drugs is reported. By using our imaging analytical method, an antiulcer effect of herbal medicine was examined on hydrochloric acid-ethanol induced gastric mucosal injury. Acetone extract of Atractylodis Rhizoma was found to have antiulcer action. In addition, the examination of fractions of the acetone extract, obtained through column chromatography, indicated that atractylon, at 17.5 mg/kg, p.o. significantly inhibits gastric mucosal injury.

Animals↗

Reduced high harmonic power spectra in patients with old myocardial infarction.

Acceleration of blood flow ejected from the ventricle into the aorta and the hydraulic power state of blood flow in the aorta may be affected by asynchronous or locally depressed contraction of the left ventricle as well as by arterial impedance. In order to evaluate the effect of an infarcted heart on the hydraulic power state of blood flow, the aortic input impedance spectrum and the hydraulic power spectrum were calculated from simultaneous recordings of pulsatile aortic pressure and flow velocity at the aortic root in 6 normal controls (group 1), 6 patients with old myocardial infarction (OMI) without aneurysm (group 2), and 6 patients of OMI with aneurysm (group 3). The ratios (Rh) of power in high harmonics to that of fundamental harmonics, that is, Rh = (E2 + E3 + ...E10)/E1, where E represents hydraulic power and the numbers represent harmonic numbers, were 0.64 +/- 0.17, 0.23 +/- 0.09, and 0.22 +/- 0.10 in groups 1, 2, and respectively (p less than 0.001 between groups 1 and 2; p less than 0.001, between groups 1 and 3). As the acceleration of ejecting flow of blood by the left ventricle is inversely related with arterial impedance, Rh will be also inversely related with arterial impedance. Then, the product of Rh and the characteristic impedance (Zc) would be an indicator of the left ventricular contractility. In fact, the products were 64 +/- 15, 32 +/- 14, and 31 +/- 13 dyne.sec.cm-5 in groups 1, 2, and 3 respectively (p less than 0.005, between groups 1 and 2; p less than 0.005, between groups 1 and 3). These results suggest that asynchronous or locally depressed contractions of the left ventricular wall are closely related to depressed Rh and further to depressed values of the products of Rh and Zc. It is concluded that analysis of the power spectrum of blood flow in the root of the aorta provides information of the left ventricular contractility in connection with arterial impedance.

Blood Flow Velocity↗