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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 145 records · Page 8Linked to original sources

[MR imaging of bone and soft tissue tumors].

One hundred sixty-one patients with tumors of bone or soft tissues underwent MRI. We believe to be able to differentiate benign from malignant lesions on the basis of imagings at internal, marginal, and peripheral properties. MR imagings demonstrated specific morphologic features that suggest the correct tissue diagnosis. MR imagings with STIR method or Gd-DTPA were more valuable. Because of the high contrast between the tumors and normal tissue, especially by STIR method, MRI provides improved detection and delineation of bone soft tissue tumors when compared to other diagnostic modalities.

Bone Neoplasms

[Dynamic CT under angiotensin II-induced hypertension--application for the differential diagnosis between benign and malignant solid ovarian tumors].

Dynamic CT was applied to 9 patients with solid ovarian tumors of an unknown nature after ultrasonography and tumor marker tests with CA125, TPA and IAP. Dynamic CT was performed under the condition of normotension and angiotensin II (AT II)-induced hypertension. The results obtained were as follows. 1. Intratumoral blood flow increased 25 percent in patients with malignant tumors, decreased 7 percent in tumors of low potential malignancy, and increased 6 percent in patients with benign tumors due to the pressor effect of AT II. 2. Changes in intratumoral blood flow were not uniform in various parts of a malignant tumor. 3. Differential diagnosis of malignant and benign tumors and tumors of low potential malignancy was possible by this method. 4. The results indicated that chemotherapy under AT II-induced hypertension would have a better effect on the treatment of malignant ovarian tumors.

Adult

[Blood flow measurement with impedance plethysmography--experimental and clinical application in orthopaedic surgery].

Impedance plethysmography has been used clinically to measure the cardiac output. We have improved the apparatus of impedance plethysmography and applied it in the orthopaedic field. It is now possible to measure the blood flow in human fingers and in the extremities of rabbits. Experimentally, we measured the blood flow through the rabbit extremities with the measured values reflecting the ischemic condition. Clinically, we measured the blood flow through the fingers with arteriosclerosis obliterans with the measured values consistent with the angiographic findings. The measurement of blood flow in vascular injuries and attachment of fingers reflected the ischemic condition. By using the impedance plethysmography, we cannot obtain an absolute value because the measured value is affected by the type of electrode and the position of the electrode. We can nevertheless seek a relative value by comparing with the values at normal site. We can also identify any differences before and at the after change in blood flow. When the advantages and disadvantages of this method are better understood, this method will be of wide clinical use.

Animals

Identification of a disaccharide (Xyl-Glc) and a trisaccharide (Xyl2-Glc) O-glycosidically linked to a serine residue in the first epidermal growth factor-like domain of human factors VII and IX and protein Z and bovine protein Z.

We have recently described a unique trisaccharide linked to a serine residue in the first epidermal growth factor-like domains of bovine blood coagulation factors VII (Ser-52) and IX (Ser-53) (Hase, S., Kawabata, S., Nishimura, H., Takeya, H., Sueyoshi, T., Miyata, T., Iwanaga, S., Takao, T., Shimonishi, Y., and Ikenaka, T. (1988) J. Biochem. (Tokyo) 104, 867-868). The sugar chain identified in these clotting factors consists of 1 mol of hexose (glucose (Glc] and 2 mol of pentose (xylose (Xyl]. We report here that human factors VII and IX and protein Z and bovine protein Z also contain such carbohydrate moieties linked to a serine residue at the same position found in bovine factors VII and IX. A glycopeptide derived from each of these proteins was subjected to amino acid sequence and component sugar analyses and fast atom bombardment mass spectrometric analysis. The results indicate that the glycopeptide derived from human factor IX contains 1 mol each of Glc and Xyl. The reducing end of this disaccharide was identified as Glc by analyzing the disaccharide generated by hydrazinolysis. In contrast, human factor VII and protein Z yielded two different glycopeptides which contained Glc and Xyl at molar ratios of 1:1 and 1:2, respectively, suggesting microheterogeneity of these O-linked sugar chains. Bovine protein Z glycopeptide contained 1 mol of Glc and 2 mol of Xyl. These sugar compositions were confirmed by analyses of the intact proteins. In relation to the trisaccharide sugar chain previously discovered in bovine factors VII and IX, these findings indicate the existence of a Xyl2-Glc-Ser and a Xyl-Glc-Ser structure in the first epidermal growth factor-like domains of human factors VII and IX and protein Z in addition to that of bovine protein Z. Whether these carbohydrate moieties contribute to the biological activities of these proteins is unknown.

Amino Acid Sequence

Photoaffinity labeling of thiamin-binding component in yeast plasma membrane with [3H]4-azido-2-nitrobenzoylthiamin.

When prepared from Saccharomyces cerevisiae through an acid precipitation at pH 5.0 for a crude particulate fraction obtained by mechanical agitation of yeast protoplasts with glass beads, the plasma membranes have more remarkable binding quantities of [14C]thiamin (Kd, 51 nM; Bmax, 263 pmol per mg of protein) compared with our previously prepared membranes [(1986) Experientia 42, 607-608]. Photoaffinity labeling of these yeast plasma membranes with [3H]4-azido-2-nitrobenzoylthiamin resulted in the covalent modification of a membrane component with an apparent molecular mass of 6-8 kDa. The extent of its labeling was markedly decreased by previous addition of thiamin. This result suggests that the small membrane component (6-8 kDa) takes part in the thiamin binding of thiamin carrier protein(s) in yeast plasma membranes.

Acid Phosphatase

Cytotoxicity of interleukin 2-toxin toward lymphocytes from patients with adult T-cell leukemia.

The inhibitory effect of a diphtheria toxin-related interleukin 2 fusion protein, IL-2-toxin, on protein synthesis in adult T-cell leukemia/lymphoma (ATL) cells was examined in vitro. Peripheral blood ATL cells from 12 patients (six acute type, four chronic type, and two smoldering type ATL) and the lymph node cells from three ATL patients (two acute type and one lymphoma type ATL) were examined. At a concentration of 10(-8) M, IL-2-toxin inhibited protein synthesis by 60 to 98% in lymph node ATL cells, whereas protein synthesis in peripheral blood ATL cells was inhibited from 20 to 57% in acute type, and from 3 to 13% in chronic type. In contrast, IL-2-toxin had no measurable effect on T-cells from either patients with smoldering type ATL or normal controls. The cytopathic effects of IL-2-toxin were blocked by the addition of anti-CD25 monoclonal antibody, suggesting that the inhibition of protein synthesis in target cells was mediated by the IL-2 receptor (IL-2R). The degree of inhibition of protein synthesis, however, was not closely correlated with expression of CD25 antigen (low-affinity Mr 55,000 glycoprotein, IL-2R, Tac antigen) on ATL cells. There was an apparent correlation between the degree of inhibition and the rate of protein synthesis in ATL cells. We demonstrate that ATL cells from patients with acute or lymphoma type disease were more sensitive to IL-2-toxin than cells from chronic or smoldering disease. These findings suggest that the high affinity IL-2R present on acute and lymphoma type ATL cells may serve as a target for therapy with this recombinant chimeric toxin.

Adult

A possible role for acid phosphatase with thiamin-binding activity encoded by PHO3 in yeast.

Periplasmic soluble thiamin-binding protein in Saccharomyces cerevisiae (Iwashima, A. et al. (1979) Biochim. Biophys. Acta 577, 217-220) was demonstrated to be encoded by PHO3 gene that codes for thiamin repressible acid phosphatase (Schweingruber, M.E. et al. (1986) J. Biol. Chem. 261, 15877-15882) by genetic analysis. The pho3 mutant cells of S. cerevisiae in contrast to the parent cells have markedly reduced activity of the uptake of [14C]thiamin phosphates, suggesting that thiamin repressible acid phosphatase plays a role in the hydrolysis of thiamin phosphates in the periplasmic space prior to the uptake of their thiamin moieties by S. cerevisiae.

Acid Phosphatase

Profiles of expression of activated cell antigens on peripheral blood and lymph node cells from different clinical stages of adult T-cell leukemia.

The expression of activated cell antigens (Ags) on adult T cell leukemia (ATL) cells at different clinical stages (acute, chronic, and smoldering), and ATL cells from enlarged lymph nodes were studied using monoclonal antibodies (MoAbs). The expressions of CD25 (Tac), CD28, T9 (transferrin receptor), and Ki-67 (proliferating cell nuclear antigen) Ags were high, and that of CD7 Ag was low in both acute and chronic ATL cells compared with that in normal T cells. The expressions of T9 and Ki-67 Ags were higher in acute ATL cells than in chronic ATL cells. The expression of CD38 Ag was higher in acute ATL cells but not in chronic ATL cells compared with normal T cells. On the contrary, the expression of HLA-DR Ag on the cell surface and the transcript of the HLA-DR Ag gene were high in chronic ATL cells, but not in acute ATL cells. A high percentage of lymph node ATL cells expressed T9, CD38, and Ki-67 Ags, although the peripheral blood ATL cells of the same patients showed significantly lower levels of expression of the same Ags. Interestingly, CD7 and HLA-DR Ags were detected on the majority of lymph node ATL cells. Moderately high percentage of smoldering ATL cells expressed CD25, CD28, and HLA-DR Ags, though a few numbers of leukemic cells were present in the samples. These findings confirm that the modes of activation of ATL cells in different clinical stages differ, and suggest that the differences might be reflected in the clinical features. The low expression of HLA-DR Ag in acute ATL cells, despite high expression of the Ag in chronic ATL cells, suggests that successive events that suppress HLA-DR Ag expression are necessary for the transformation of chronic ATL cells into acute ATL cells. Moreover, the high expressions of T9, CD38, Ki-67, CD7, and HLA-DR Ags on lymph node ATL cells indicate that ATL cells preferentially proliferate in lymph nodes.

Antibodies, Monoclonal

Quantitative immunohistochemistry of metallothionein in rat placenta.

The presence of metallothionein (MT) was demonstrated in placentae from cadmium-exposed and control rats by an immunohistochemical technique, using peroxidase as label and the diaminobenzidine procedure for the staining reaction. The protein was found in different regions of the placenta, i.e. in trophoblastic labyrinth, in spongiotrophoblast and in visceral yolk sac. Cytophotometric analysis of the final reaction product revealed that the amount of MT was increased in the placental labyrinth of cadmium-exposed rats. Increases were found in both nuclei and cytoplasm of trophoblast cells in the labyrinth region. Possible roles of MT in the transport of zinc and in the carbohydrate metabolism are discussed.

Animals

Peripheral hemodynamic effects of captopril in patients with congestive heart failure.

In 14 patients with severe congestive heart failure, the effects of captopril on the forearm circulation were evaluated with strain gauge plethysmography. Changes in plasma renin activity, angiotensin II, norepinephrine, epinephrine, bradykinin, prostaglandin E2, and 6-keto-prostaglandin F1 alpha concentrations were also measured. To determine whether the prostaglandins contribute to the peripheral hemodynamic response to captopril, the hemodynamic and hormonal measurements were repeated after pretreatment with indomethacin, an inhibitor of prostaglandin synthesis. Ninety minutes after administering a single dose of captopril (25 mg), mean blood pressure and venous pressure decreased (p less than 0.01 and p less than 0.05, respectively), forearm blood flow and maximum venous volume increased (p less than 0.05 for both), and forearm vascular resistance and forearm venous tone decreased (p less than 0.05 for both). Captopril also improved forearm venous distensibility (p less than 0.05). Pretreatment with oral indomethacin (50 mg) significantly blunted all of these captopril-induced hemodynamic changes. The blockage of the renin-angiotensin system by captopril was unaltered by indomethacin pretreatment. Captopril significantly increased plasma bradykinin, prostaglandin E2, and 6-keto-prostaglandin F1 alpha (p less than 0.05 for each). Indomethacin pretreatment did not affect the captopril-induced increase in bradykinin, but it did completely eliminate the increase in the prostaglandins. Plasma catecholamines did not change with captopril. These data suggest that the vasodilator prostaglandins play a significant role in captopril's peripheral vasodilative effects in congestive heart failure.

6-Ketoprostaglandin F1 alpha

Antigenic and genetic characterization of three influenza C strains isolated in the Kinki district of Japan in 1982-1983.

Three strains of influenza C virus (C/Kyoto/41/82, C/Nara/82, C/Hyogo/1/83) have been isolated from humans in the Kinki district of Japan between February 1982 and December 1983. Oligonucleotide mapping of total vRNA and antigenic analysis with anti-HE monoclonal antibodies have shown previously that they are closely similar to one another but dissimilar to any of the strains isolated in Japan before 1982. In the present study, the nucleotide sequences of the hemagglutinin-esterase (HE) genes of these three strains were determined and compared with those of the previously published strains. The results revealed that the Kinki isolates had a high nucleotide sequence homology (98.4-98.5%) with the virus isolated in 1980 in the United States (C/Mississippi/1/80). Similarity of the Kinki strains to C/Mississippi/1/80 was also confirmed by oligonucleotide mapping of total vRNA and antigenic comparison using a panel of 11 anti-HE monoclonal antibodies. The isolates from Kinki and Mississippi could be distinguished from the previously isolated strains in serological tests with heterogeneous sera, suggesting that they may have possessed epidemiological advantage in Japan around 1982-1983. These observations raise the possibility that the rapid spread of influenza C variant closely related to C/Mississippi/1/80 has occurred in Kinki in 1982-1983 presumably because this imported virus was largely different in antigenicity from the previously prevalent ones.

Antibodies, Monoclonal

Two distinct monoclonal natural thymocytotoxic autoantibodies from New Zealand black mouse.

Autoimmune-prone NZB and NZB x NZW F1 mice have a large amount of autoantibodies cytotoxic for thymocytes (natural thymocytotoxic autoantibodies, NTA). We established two distinct monoclonal NTAs (NTA260 and NTA204) from a NZB mouse that react with the majority, but not all of these thymocytes. Flow cytometry analysis showed that NTA260 is positive on subpopulations of peripheral T cells from young mice, in which approximately 65% of CD4+ and 85% of CD8+ T cells were NTA260+. NTA260 also reacted with brain tissues of mice and rats, including Purkinje cells in the cerebellum. Western blot analysis showed that the molecular weight of NTA260 antigen was 55 kDa. In contrast to NTA260, NTA204 reacted with peripheral B cells but not with peripheral T cells in mice. NTA204 also reacted with peripheral blood granulocytes and bone marrow myeloid cells from both mice and rats. An immunofluorescence inhibition assay revealed the presence of autoantibodies with specificities of each NTA260 and NTA204 in the sera from NZB mice. As a selective decline in the subset of NTA260+ T cells but not NTA204+ B cells was observed with aging of NZB and NZB x NZW F1 hybrid mice, NTA260 is at least partly related to the observed immunological abnormalities of T cells in these autoimmune-prone New Zealand mice.

Age Factors

Opposite effects of diazepam and beta-CCE on immobility and straw-climbing behavior of rats in a modified forced-swim test.

The present study was undertaken to examine how two ligands of the benzodiazepine receptor, which possess anxiolytic or anxiogenic actions, affect both the duration of immobility and the incidence of straw-climbing behavior in rats in a modified forced-swim test. Rats were injected IP with either vehicle, diazepam (0.5, 1, 5 mg/kg), or beta-carboline-3-carboxylic acid ethyl ester (beta-CCE; 0.5, 1, 2, 5 mg/kg), or a combination of diazepam at 1 mg/kg and beta-CCE at 2 mg/kg. In addition, Ro 15-1788 (1 mg/kg), a specific benzodiazepine antagonist, was injected IP 20 min after diazepam injection and immediately after beta-CCE injection, respectively. In the first 5-min period of the forced-swim test, diazepam at 5 mg/kg prolonged the duration of immobility, whereas beta-CCE at 1, 2 and 5 mg/kg reduced its duration. Immediately after the first 5-min test period, 4 straws were suspended above the surface of the water, and the number of straw-climbing attempts and the duration of immobility were measured for a subsequent 5-min test period. Straw-suspension elicited straw-climbing behavior in forced swimming rats, resulting in a shortening of the duration of immobility in this period. All doses of diazepam inhibited straw-climbing attempts and prolonged the duration of immobility in a dose-dependent manner. beta-CCE at 1 or 2 mg/kg enhanced straw-climbing attempts, but did not significantly affect the duration of immobility. Furthermore, the combined administration of diazepam and beta-CCE antagonized the respective drug effects on the duration of immobility and the number of straw-climbing attempts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Josamycin concentrations in human dental granuloma after a single oral administration of josamycin.

1. Josamycin concentrations in human serum and dental granuloma after a single oral administration of josamycin (600 mg) were assayed by an agar diffusion (paper disc) method. 2. The mean peak josamycin concentrations in serum and dental granuloma occurred at an identical time, approximately 90 min, and were 0.88 micrograms/ml and 1.61 micrograms/g, respectively. 3. The mean concentration ratio of dental granuloma to serum at the peak time was 2.24. 4. Josamycin concentration in dental granuloma at the peak time exceeded MIC80 for clinically isolated strains of Streptococcus group A, Peptostreptococcus spp., and Bacteroides spp.

Administration, Oral

The existence of aldose reductase inhibitors in some kampo medicines (Oriental herb prescriptions).

Traditionally in Japan, some kampo medicines which contain Glycyrrhizae radix (GR) and Paeoniae radix (PR) have long been used for the treatment of diabetic neuropathy. Since we have previously shown that GR und PR have potent aldose reductase inhibitory activities, we further investigated the constituents of these two. The boiled water extract of GR was applied to Sephadex LH-20 column chromatography and 6 fractions (Frs. A, B, Cs, Cp, D, and E) were obtained. Frs. Cp and D were retreated in the same manner and 7 pure compounds (GUs 1-7) were obtained. The boiled water extract of PR was fractionated with ethyl acetate followed by n-butanol and 3 fractions (Frs. 1-3) were collected. Fr. 1 was retreated in the same manner and 2 pure compounds (PRs 1 and 2) were obtained. Among the GU compounds, GU-2 was the most potent inhibitor of rat lens aldose reductase (RLAR) by inhibiting 86% at the concentration of 1.0 microgram/ml. The IC50 of GU-2 was 7.2 x 10(-7) M. Furthermore, GU-2 markedly inhibited sorbitol accumulation in human red blood cells, having an IC50 of 2.9 x 10(-5) M. GU-5 and PR-1 also inhibited RLAR (IC50: 5.6 x 10(-7) M and 6.3 x 10(-7) M, respectively). The structures of GU-2, GU-5, and PR-1 were identified as isoliquiritin, licuraside, and 1, 2, 3, 6-tetra-O-galloyl-beta-D-glucose, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase

The novel murine B cell differentiation antigen Lp-3.

The unique murine lymphocyte differentiation antigen, Lp-3, with a mol. wt of approximately 125 kd, was found using a rat monoclonal antibody. The Lp-3 antigen was distributed on a wide variety of myeloid, T cell, and B cell lineages in mice. However, the expression was only found in B cells at certain stages of differentiation. The pre-B and virgin B cells in the bone marrow from 2-month-old BALB/c mice were weakly positive for Lp-3, while the resting B cells in the spleen and lymph node were Lp-3 negative. In contrast, the majority of B cells in the peritoneal cavity, mostly Ly-1 (CD5) B cells, had a brighter fluorescence for Lp-3 than did bone marrow B cells. The Lp-3 antigen could be induced in a high density in approximately one-half of lipopolysaccharide-stimulated, large, blastic spleen B cells. Cell cycle analysis showed that Lp-3 is an early B cell activation antigen which is first expressed at the G1A phase of the cell cycle. Therefore this novel B cell differentiation antigen will be useful for differentiating pre-B and virgin B cells in the bone marrow, resting B cells, and a population of activated B cells in the periphery. In contrast to findings in BALB/c mice, there was an elevated population of B cells with a bright Lp-3 expression in the spleen of autoimmune-prone NZB x NZW F1 mice.

Animals

Cardiorenal effects of an orally active dopamine prodrug (TA-870) in patients with congestive heart failure.

The effects of TA-870, a newly synthesized orally active dopamine prodrug, on the cardiorenal functions were investigated in 12 patients with severe chronic congestive heart failure. A single oral dose of TA-870 (1,200 mg) improved left ventricular fractional shortening and mean circumferential velocity on M-mode echocardiography (p less than 0.01 for both). Renal plasma flow and glomerular filtration rate improved with TA-870 (p less than 0.01 and p less than 0.05, respectively); urine volume and sodium excretion increased (p less than 0.01 for both). Blood pressure and heart rate did not change during the 4-h experimental period. Mean plasma free dopamine levels peaked 1 h after dosing. These data suggest that the cardiorenal effects of oral TA-870 are comparable with those of continuous intravenous injections of dopamine. Thus, TA-870 appears to be a useful alternative drug to intravenous dopamine.

Adult

Effect of anti-haemagglutinin-esterase glycoprotein monoclonal antibodies on the receptor-destroying activity of influenza C virus.

Five monoclonal antibodies (J14, J9, Q5, K16, S16), directed to three distinct antigenic sites (A-1, A-2, B-1) on the haemagglutinin-esterase glycoprotein of influenza C virus, were analysed for their ability to inhibit the receptor-destroying enzyme (RDE) activity of the virus, utilizing various assay systems. The ability of influenza C virus to destroy the receptors on chicken erythrocytes was inhibited efficiently by the antibodies to site A-1 (J14, J9, Q5) but not by those to site A-2 (K16) and sit B-1 (S16). Of the three antibodies to site A-1, J14 showed the highest inhibitory activity. Antibodies to sites A-1 and A-2 inhibited the ability of RDE to inactivate the haemagglutination inhibition activity of rat serum inhibitors, but the highest activity was observed again with J14. Thus the RDE site of influenza C virus may be located closest to the epitope recognized by J14. The removal of O-acetyl groups from either 9-O-acetyl-N-acetylneuraminic acid or p-nitrophenylacetate, caused by the viral RDE, was not prevented at all by any of the monoclonal antibodies tested. Furthermore, none of several polyclonal antiviral sera prepared in different animal species was able to block the hydrolysis of these small substrates, raising the possibility that the catalytic site of influenza C viral RDE is antigenically silent.

Acetylesterase