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Biomedical subjects

H Fujiwara

Publications and source records attributed to H Fujiwara.

At least 19 recordsLinked to original sources
PubMed1992

Adult coronary artery disease probably due to childhood Kawasaki disease.

We have surveyed adult survivors of childhood Kawasaki disease (KD) who had coronary artery disease that could be ascribed to KD. In response to questionnaires sent to cardiologists throughout Japan, 21 patients (17 men, 4 women, aged 20-63 years) with coronary lesions and a definite (2) or suspected (19) history of KD were reported. 5 patients had presented with acute myocardial infarction, 6 previous myocardial infarction, 9 angina pectoris, and 1 dilated cardiomyopathy. 16 patients had obstructions in two or more coronary arteries. 3 had died and 18 were alive with serious sequelae (mitral regurgitation, arrhythmias, congestive heart failure). Childhood KD should be included in the differential diagnosis of coronary artery disease in young adults.

Adult↗
PubMed1992

Instability of assembled T-cell receptor complex that is associated with rapid degradation of zeta chains in immature CD4+CD8+ thymocytes.

The intracellular fate of newly synthesized T-cell receptor (TCR) chains was compared in CD4+CD8+ (double positive; DP) thymocytes and in CD4+CD8- or CD4-CD8+ (single positive; SP) thymocytes. Purified DP and SP thymocytes from normal adult mice were analyzed by pulse-chase metabolic labeling and immunoprecipitation with specific anti-TCR antibodies. Biosynthesis of invariant chains (CD3 gamma, -delta, -epsilon, and zeta) was comparable between DP and SP thymocytes, whereas DP thymocytes synthesized TCR alpha and TCR beta chains at lower and higher levels than SP thymocytes, respectively. These newly synthesized TCR chains were degraded at different rates in SP thymocytes based on their sensitivities for degradation as previously reported: TCR alpha, TCR beta, CD3 gamma, and CD3 delta chains were rapidly degraded and CD3 epsilon and zeta chains were stable. Although the degradation rates of clonotypic and invariant CD3 chains were similar in DP and SP thymocytes, the zeta subunit was rapidly degraded in DP thymocytes (t1/2, approximately 1.5 hr). Degradation of zeta was inhibited by NH4Cl, implicating lysosomes as the site of degradation. Comparison of TCR subunit assembly in DP and SP thymocytes demonstrated that, despite the same relative rate of formation of TCR complexes in a pulse period (30 min), complete complexes were unstable and degraded during the subsequent 6 hr of chase in DP thymocytes. This contrasted with the stability and a progressive increase in the levels of completely assembled complexes in SP thymocytes. Thus, these results demonstrate that a unique posttranslational regulation operates in the formation of TCR complexes in DP thymocytes and that lack of stability of complete TCR complexes is a crucial mechanism that may account for the limited surface TCR expression on this thymocyte subset.

Ammonium Chloride↗
PubMed1992

Particular types of tumor cells have the capacity to convert transforming growth factor beta from a latent to an active form.

We investigated the capacities of various tumor types to generate an active versus latent form of transforming growth factor beta (TGF-beta) in its culture supernatants (SNs). Tumor cell lines were divided into three types depending on the form and magnitude of TGF-beta detected in their culture SNs: some (2 of 7 lines) generated mostly an active form (Type A); others (4 of 7) generated exclusively a latent form (Type B); and the remaining line (1 of 7) produced only marginal levels of active/latent TGF-beta (Type C). When Type A tumor cells were cultured at lower numbers, cultures failed to generate active TGF-beta. However, the addition of Type B tumor cell culture SNs containing only a latent form of TGF-beta resulted in the generation of the potent activity of active TGF-beta. This capacity was observed for another Type A tumor but not for other types (Type B and Type C). An active form of TGF-beta was detected in culture SNs of Type A tumor cells as early as 3-6 h after the addition of Type B tumor culture SNs. The emergence of an active form of TGF-beta was also observed in cultures of Type A tumor cells, the protein synthesis of which was almost completely inhibited by pretreatment with cycloheximide. Moreover, the Type B tumor SN used for the induction of active TGF-beta activity was found to contain latent TGF-beta with an apparent molecular weight of about 200,000. Type A tumor cells were also capable of generating active TGF-beta by the addition of recombinant TGF-beta of latent form with a small molecular weight (about 60,000), although the generation of active TGF-beta was much weaker after the addition of small latent TGF-beta than after the addition of large latent TGF-beta. Taken collectively, these results indicate that particular types of tumor cells have the capacity to generate an active form of TGF-beta and that such capacity can be attributed to their potential to convert TGF-beta from a latent (mainly large type) to an active form.

Animals↗
PubMed1992

Low concentration endothelin-1 enhanced histamine-mediated bronchial contractions of guinea pigs in vivo.

Endothelin-1 (ET-1) represents one of the most potent constrictors of guinea pig bronchial smooth muscle. In our study, various doses of aerosolized ET-1 increased airway resistance. But a very low concentration of ET-1 (10(-12) M) could not change airway resistance. We examined low doses of ET-1 enhanced the sensitivity of bronchial contractions to histamine. ET-1 may play one of the most important roles in contributing directly or indirectly to the pathogenesis of bronchial asthma.

Aerosols↗
PubMed1992

Energy aspects of oil/water partition leading to the novel hydrophobic parameters for the analysis of quantitative structure-activity relationships.

Partition properties, that is partition coefficients and enthalpies (delta Hp degree) and entropies (delta Sp degree) of partition, have been measured for 50 benzoic acids in the 1-octanol/water system, and their role in QSAR (quantitative structure-activity relationship) analysis examined. The novel hydrophobic parameters have been introduced as a result of the separation of the Gibbs free energy term into the corresponding enthalpy and entropy terms. Application of these novel parameters to some available biological activity data supported the usefulness of these parameters in QSAR analysis. Relative contributions of the enthalpy and entropy terms are also discussed.

Benzoates↗
PubMed1992

Type II collagen-induced murine arthritis: induction of arthritis depends on antigen-presenting cell function as well as susceptibility of host to an anticollagen immune response.

Two sets of ((resistant x susceptible) F1----parent) and (parent----F1) chimeric mice were prepared. In the chimeric combinations involving BALB/c and DBA/1 mice, all (F1----F1) chimeras developed arthritis as well as potent anticollagen responses after immunization with collagen, whereas all (F1----BALB/c) and (BALB/c----F1) chimeras induced neither arthritis nor immune responses. This type of F1 T cells could be activated with APC from DBA/1 but not from BALB/c mice. Thus, the failure of the [F1 in equilibrium with BALB/c] chimeras to mount anticollagen responses was due to a defect at the APC level. Another arthritis-resistant strain, C57BL/6, exhibited adequate APC function, but reduced T cell responsiveness, representing an intermediate responder. In the chimeric combinations involving C57BL/6 and DBA/1 mice, (F1----F1) and (C57BL/6----C57BL/6) chimeras developed very high and very low incidence of arthritis, respectively. (C57BL/6----F1) chimeras developed an appreciable incidence of arthritis under conditions in which this group of chimeras generated intermediate levels of anticollagen responses. In contrast, (F1----C57BL/6) chimeras developed low incidence of disease despite induction of strong responses. Moreover, cells from collagen-immunized (F1----C57BL/6) chimeras, when transferred into T cell-depleted B cell mice of F1 or C57BL/6 strain, produced comparable immune responses in both groups but induced much more severe arthritis in F1 than in C57BL/6 recipients. These results indicate that: i) two types of arthritis-resistant strains can be identified, each of which has anticollagen APC defect as a low responder and reduced T cell responsiveness as an intermediate responder and ii) a discrepancy between the degree of anticollagen responses and clinical arthritis is attributed to the differential susceptibility to anticollagen immune responses.

Animals↗
PubMed1992

Tumor-bearing mice exhibit a progressive increase in tumor antigen-presenting cell function and a reciprocal decrease in tumor antigen-responsive CD4+ T cell activity.

Splenic CD4+ T cells from BALB/c mice bearing a syngeneic tumor (CSA1M) 2 to 3 wk after the inoculation with CSA1M cells produced IL-2 and macrophage-activating factor upon in vitro cultures. This lymphokine production was achieved without stimulation of these T cells with exogenous stimulating tumor Ag. However, elimination of APC from spleen cells resulted in almost complete abrogation of the capacity of CD4+ T cells to produce IL-2/macrophage-activating factor. The lymphokine production was regained when APC from CSA1M-bearing mice were added back to cultures. APC from normal or another syngeneic tumor (Meth A)-bearing mice failed to regain the lymphokine production. These observations demonstrated that the lymphokines were produced by CD4+ T cells from CSA1M-bearing hosts through their collaboration with APC binding CSA1M tumor Ag in the tumor-bearing state. The lymphokine-producing capacity of whole spleen cells from tumor-bearing mice reached the maximal level around 2 to 3 wk after tumor implantation but gradually decreased with the progress of tumor-bearing stages. Importantly, tumor-bearing stage-related changes were observed in a different fashion in the capacities of anti-CSA1M CD4+ T cells vs CSA1M tumor Ag-binding APC. The capacity of APC increased with the progress of tumor-bearing stages as demonstrated by the stimulation of CSA1M-immunized T cells with APC from different CSA1M-bearing stages. In contrast, the reactivity of anti-CSA1M T cells to APC from a given CSA1M-bearing stage decreased with the tumor-bearing stage. These results demonstrate a stage-related increase tumor Ag-binding APC function, as well as a reciprocal reduction in tumor Ag-responsive CD4+ T cell activity.

Animals↗
PubMed1992

Cell-cell interaction in graft rejection responses: induction of anti-allo-class I H-2 tolerance is prevented by immune responses against allo-class II H-2 antigens coexpressed on tolerogen.

The intravenous sensitization of C57BL/6 (B6) mice with class I H-2-disparate B6-C-H-2bm1 (bm1) spleen cells results in almost complete abrogation of anti-bm1 CD8+ helper (proliferative and interleukin 2-producing) T cell (Th) activities. Although an appreciable portion of CD8+ cytotoxic T lymphocyte (CTL) precursors themselves remained after this regimen, such a residual CTL activity was eliminated after the engrafting of bm1 grafts, and these grafts exhibited prolonged survival. In contrast, the intravenous sensitization with (bm1 x B6-C-H-2bm12 [bm12])F1 cells instead of bm1 cells failed to induce the prolongation of bm1 graft survival as well as bm12 and (bm1 x bm12)F1 graft survival. In the (bm1 x bm12)F1-presensitized B6 mice before as well as after the engrafting of bm1 grafts, anti-bm1 CTL responses that were comparable to or slightly stronger than those observed in unpresensitized mice were induced in the absence of anti-bm1 Th activities. bm1 graft survival was also prolonged by intravenous presensitization with a mixture of bm1 and bm12 cells but not with a mixture of bm1 and (bm1 x bm12)F1 cells. The capacity of CD4+ T cells to reject bm12 grafts was eliminated by intravenous presensitization with antigen-presenting cell (APC)-depleted bm12 spleen cells. However, intravenous presensitization with APC-depleted (bm1 x bm12)F1 cells failed to induce the prolongation of bm1 graft survival under conditions in which appreciably prolonged bm12 graft survival was induced. More surprisingly, bm1 graft survival was not prolonged even when the (bm1 x bm12)F1 cell presensitization was performed in CD4+ T cell-depleted B6 mice. This contrasted with the fact that conventional class I-disparate grafts capable of activating self Ia-restricted CD4+ as well as allo-class I-reactive CD8+ Th exhibited prolonged survival in CD4+ T cell-depleted, class I-disparate cell-presensitized mice. These results indicate that: (a) intravenous presensitization with class I- and II-disparate cells fails to reduce anti-allo-class I rejection responses that would otherwise be eliminated using only class I-disparate cells; (b) such failure is generated according to the coexpression of both classes of alloantigens on a single cell as tolerogen; and (c) allo-class II antigens coexpressed on tolerogen function to activate CD4+ as well as non-CD4+ Th leading to the generation of anti-class I effector T cell responses.

Animals↗
PubMed1992

Utility of liquid chromatography/fast atom bombardment mass spectrometry and liquid chromatography/thermospray mass spectrometry for structure identification of metabolites of a fluorinated herbicide.

This study demonstrates a useful application of on-line microbore high-performance liquid chromatography (HPLC) fast atom bombardment (FAB) and thermospray (TSP) mass spectrometry techniques for identification of metabolites from the in vitro metabolism of an experimental Monsanto herbicide: 2-chloro-N-(ethoxymethyl-N-[2-methyl-6- (trifluoromethyl)phenyl]acetamide, 'chloroacetanilide'. The microbore HPLC FAB technique on a high-resolution sector mass spectrometer accelerated identification of polar metabolites from the in vitro metabolism study of the herbicide. It provided good chromatographic resolution and excellent FAB sensitivity with strong protonated molecular ions. Scanning high-resolution LC/FAB mass spectrometry also provided molecular formulae for structural elucidation of unknown metabolites. Sample purification and concentration were minimized. Identification of less polar metabolites was carried out using LC/TSP mass spectrometry with a quadrupole mass spectrometer. LC/TSP mass spectrometry provided useful structural information for both polar and less polar metabolites because their spectra showed more fragmentation than FAB spectra. Glutathione conjugation was the major reaction observed during in vitro incubation of the herbicide. Oxidation of the chloroacetanilide by rat liver enzymes was also a significant metabolic reaction. Seven metabolites were identified, of which four were glutathione conjugates.

Acetamides↗
PubMed1992

The basal interhemispheric approach for acute anterior communicating aneurysms.

We reviewed the surgical outcome in 85 patients with ruptured anterior communicating artery (ACoA) aneurysms, who were operated on within 72 hours of onset via a basal interhemispheric (BIH) approach (Group 1, N = 48), or an anterior interhemispheric (AIH) approach (Group 2, N = 37). The age, sex ratio and pre-operative grade (Gr) were similar for both groups. The outcome at the time of discharge was as follows for group 1: excellent or good 88%; fair, 6%; vegetative state, 2% and death 4%. For group 2, it was: excellent or good 78%; fair, 16%; vegetative state, 3%; and death, 3%. A significant correlation between admission grade and outcome was found in both groups. The outcome in group 1 was better than in group 2 for patients with a Glasgow Outcome Scale (GOS) better than fair (p < 0.07). No patient in group 1 had postoperative anosmia, but nine patients in group 2 became anosmic. The total number of complications was also significantly less in group 1. Our overall mortality rate was 4%. In conclusion, the BIH approach was more beneficial for treating acute ACoA aneurysm.

Adult↗
PubMed1992

Tumor-immunotherapy with the use of tumor-antigen-pulsed antigen-presenting cells.

Our previous study demonstrated that the administration of antigen-presenting cells (APC) pulsed with tumor cell membrane fraction to naive syngeneic mice results in effective induction of tumor-specific protective immunity in vivo. The present study examined whether tumor-antigen-pulsed APC can produce the inhibitory effect on the growth of tumor cells when administered to tumor-bearing hosts. Naive BALB/c mice were inoculated with viable tumor cells. Five days later, these mice started to receive the relevant tumor-antigen-pulsed APC at 3- to 4-day intervals. The administration of tumor-antigen-pulsed APC induced the rejection or growth inhibition of a growing tumor in approximately half of the recipient mice. Moreover, it was demonstrated that tumor-specific immunity was induced in such tumor-regressed mice. These results indicate that tumor-antigen-pulsed APC are effectively applicable to the tumor-specific immunotherapy.

Animals↗
PubMed1992

Protective effect of carteolol, a beta-blocker, on myocardial cellular damage in ischemic and reperfused pig hearts: assessment with gated in vivo 31-phosphorus magnetic resonance spectroscopy and electron microscopy.

To assess the effect of carteolol, a beta-blocker, on ischemia and reperfusion, changes in the ultrastructure of myocytes and energy metabolism were studied by 31P-NMR in 41 pig hearts without collateral circulation. The left anterior descending coronary artery was occluded for 20 min and reperfused for 120 min in three groups: seven pigs (group 1, no treatment with carteolol; group 2, pre-ischemia treatment with carteolol (10 micrograms/kg); group 3, post-ischemia treatment with carteolol before reperfusion). Other groups of five pigs were killed after 120 min of ischemia (group 4, no treatment; group 5, pre-ischemia treatment) or 20 min of ischemia (group 6, no treatment; group 7, pre-ischemia treatment). After 20 min of ischemia, ATP was higher in groups 2 (76 +/- 9% of the baseline value) than in group 1 (59 +/- 5%) and group 3 (60 +/- 10%). However, the difference disappeared after 30 min of ischemia. After 120 min of reperfusion, ATP showed much better recovery in group 2 (92 +/- 9%) than in groups 1 (66 +/- 7%) and 3 (68 +/- 10%). Ischemic injury, as viewed by light and electron microscopy, was milder in group 7 than in group 6 after 20 min occlusion, but the myocytes were almost normal after 120 min reperfusion in groups 1 to 3. The heart rate, blood pressure and rate pressure product showed no significant difference among the groups. These results indicate that pre-ischemia treatment with carteolol provided protection against ischemic cellular injury and accelerated the repletion of ATP during reperfusion, but the post-ischemia treatment did not lead to recovery of ATP. Therefore, the favorable effect during reperfusion of pre-ischemia treatment with carteolol depends on its protective effect during ischemia.

Adenosine Triphosphate↗
PubMed1992

Comparative studies of sulpiride and classical neuroleptics on induction of catalepsy, locomotor activity, and brain dopamine metabolism in mice.

The effects of the peripheral administration of sulpiride on the induction of catalepsy, the vertical (VMA) and horizontal (HMA) locomotor activities, and on the dopamine metabolism in the limbic system, striatum, and nucleus accumbens were examined using mice up to 7.5 h after administration of drugs. These effects were compared to those of pimozide and haloperidol. Sulpiride (1.25-160 mg/kg, IP) clearly induced catalepsy similar to pimozide (0.0625-4 mg/kg, IP) and haloperidol (0.0375-0.3 mg/kg, IP). During the induction of catalepsy, the intensity was the strongest at 4.5 h after administration and the ED50 value showed 11.5 mg/kg at that time. However, a moderate dose of sulpiride at 10-20 mg/kg did not show the induction of a dose- and time-dependent catalepsy. During the locomotor activity, the VMA was significantly inhibited at 1.5 h and 6 h after administration of pimozide (0.25 mg/kg, IP) and haloperidol (0.075 mg/kg, IP) as compared to the control group, while the HMA was significantly inhibited at 1.5 h after administration of sulpiride (40 mg/kg, IP) and pimozide (0.25 mg/kg, IP). Subsequently, in the dopamine metabolism, sulpiride, pimozide, and haloperidol: 1) considerably accelerated the turnover in the dopamine metabolism in three distinct brain areas; 2) increased the levels of the DOPAC, HVA, and 3-MT even 6 h after administration, as well as at 1.5 h after administration; and 3) decreased the levels of dopamine in the nucleus accumbens at 1.5 h after administration. These results indicate that sulpiride displays a mode of action different from pimozide and haloperidol with regard to the induction of catalepsy, but not with regard to the locomotion and brain dopamine metabolism.

Animals↗
PubMed1992

Hypoxia modulates mediator responses and neurotransmission in guinea-pig trachea in vitro.

To discover whether hypoxia affects mediator responses and neurotransmission in tracheal smooth muscle, we studied in vitro tracheal segments from guinea-pigs under isometric conditions. Hypoxia itself did not alter the basal tone. The maximum response to acetylcholine and histamine under hypoxia was less than that under oxygenated conditions. The logarithm of 50% effective concentration (log EC50) of the response to acetylcholine under hypoxia was not altered, but the log EC50 of the response to histamine decreased significantly. In contrast to the response to exogenous acetylcholine, the maximum contractile response to electrical field stimulation (EFS) under hypoxia was not different from that under oxygenated conditions, but the logarithm of 50% effective frequency of contractions caused by EFS under hypoxia decreased significantly. On the other hand, non-adrenergic-non-cholinergic relaxation caused by EFS was unaffected by hypoxia. These observations suggest that hypoxia can modulate the responses of tracheal smooth muscle to acetylcholine, histamine and nerve stimulation.

Acetylcholine↗
PubMed1992

Effects of a sustained thromboxane synthase inhibition on exercise-induced changes in eicosanoid formation, catecholamine concentration, and platelet aggregation in humans.

In an effort to characterize an interaction between the eicosanoids and sympathoadrenal system on platelet aggregation, we tried to determine if a sustained thromboxane A2 (TXA2) synthase inhibition would modulate changes in eicosanoid formation, catecholamine concentration, and platelet aggregation induced by a physical stress. We measured thromboxane B2 (TXB2), 11-dehydro-TXB2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), norepinephrine, and epinephrine in vivo and platelet aggregation ex vivo before and after a treadmill exercise with and without the oral doses (400 mg twice daily for 7 days) of a new selective TXA2 synthase inhibitor (DP-1904) in nine healthy male subjects. The exercise tests performed on the pretreatment day (day 0) and posttreatment day (day 7) gave a similar result. DP-1904 caused a decrease in serum and urinary TXB2 and urinary 11-dehydro-TXB2 (p less than 0.001 to p less than 0.01) and an increase in serum 6-keto-PGF1 alpha (p less than 0.001 to p less than 0.05) throughout the dosing interval on days 4 and 7. Despite the drug effect on eicosanoid formation at rest and after exercise, the exercise-induced plasma norepinephrine and epinephrine concentrations did not differ between days 0 and 7. The 7-day treatment decreased (p less than 0.01) platelet aggregation induced both by adenosine diphosphate and by collagen at rest. However, the exercise increased (p less than 0.01) platelet aggregation by the two aggregators, resulting in the disappearance of the drug-induced antiaggregatory effects observed at rest. The treatment with a TXA2 synthase inhibitor does not appear to attain the antithrombotic action during an exercise despite the occurrence of a sustained endoperoxide shunting.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Pattern of the action of a suppressor factor produced by a human macrophage-like cell line, U937.

A U937 suppressor factor (U937SF) was purified from crude supernatant by sequential chromatography using fast protein liquid chromatography. The molecular weight and isoelectric point of U937SF were 69 kDa and 4.5, respectively. The U937SF preparation inhibited the proliferative response in human PBMC stimulated with an antigen tuberculin purified protein derivative, tetanus toxoid) or a mitogen (phytohaemagglutinin concanavalin-A). U937SF depressed both interleukin-2 (IL-2) production and IL-2 receptor (CD25) expression in peripheral blood mononuclear cells (PBMC) stimulated with an antigen but not with a mitogen. Anti-CD3 monoclonal antibody-induced responses including a proliferative response, IL-2 production and CD25 expression were suppressed by U937SF. In contrast, U937SF did not affect monocyte functions such as antigen processing and IL-1 production. Neither did it modulate the expression of T cell receptor (TCR) or CD3 molecules on the surface of lymphocytes. Moreover it did not inhibit CD25 expression in PBMC stimulated with phorbol myristate acetate plus A23187. These results suggest that U937SF prevents both IL-2 production and CD25 expression in lymphocytes activated through the TCR/CD3, but not through the other receptors or molecules. In addition, U937SF does not block the early activation events following TCR-mediated stimulation, nor affect the pre-TCR activation steps.

CD3 Complex↗
PubMed1992

Modified preservation of all annular-papillary continuity in replacement of the calcified mitral valve.

The technique described here is a modification of the mitral valve replacement with preservation of chordae tendineae for calcified mitral stenosis. After commissurotomy, the middle portion of the anterior leaflet is excised to get two parts with accessible chordal insertion. Each thickened and calcified segment is debrided by means of an ultrasonic tool and then attached to the mural leaflet. Finally mitral valve replacement is carried out. This procedure will extend surgical indication of chordae-sparing methods in mitral valve replacement for mitral stenosis.

Calcinosis↗