Biomedical subjects

T Tsuji

Publications and source records attributed to T Tsuji.

At least 415 records · Page 23Linked to original sources

PubMed1997

The antithrombotic effect of synthetic low molecular weight human factor Xa inhibitor, DX-9065a, on He-Ne laser-induced thrombosis in rat mesenteric microvessels.

The effect of a synthetic low molecular weight factor Xa (FXa) inhibitor, DX9065a, on thrombosis in vivo were examined in a rat animal model using a Helium-Neon (He-Ne) laser method. DX-9065a administered either intravenously or orally promoted anti factor Xa activity in a dose dependent manner. Anti Xa activity was maximal immediately after intravenous injection and persisted for approximately 30 minutes. Inhibitory activity was maximal 15-30 minutes after oral administration and persisted for approximately 90 minutes. Similarly DX-9065a inhibited platelet-rich thrombosis formation in mesenteric arterioles and venules. In these instances inhibition was relatively transient after intravenous injection (10-20 minutes), but persisted for more than 3 hours after oral administration. The minimum effective doses of DX-9065a given intravenously and orally were 3.89 mg/kg and 25.9 mg/kg, respectively. The results confirmed that DX-9065a selectively modulates thrombotic mechanisms, and suggest that development of this synthetic FXa antagonist could constitute an effective intravenous and oral antithrombotic agent.

Animals↗

PubMed1997

Relation of iodine-123 metaiodobenzylguanidine myocardial scintigraphy to endomyocardial biopsy findings in patients with dilated cardiomyopathy.

BACKGROUND: Iodine-123 metaiodobenzylguanidine (123I-MIBG) concentrates in adrenergic neurons and has been developed for evaluation of the sympathetic nervous system. Recent studies have demonstrated that the normal heart is clearly visualized by 123I-MIBG cardiac scintigraphy, whereas abnormal 123I-MIBG myocardial uptake and washout have been demonstrated in patients after myocardial infarction and in patients with congestive cardiomyopathy, long QT syndrome, and ventricular tachycardia. HYPOTHESIS: Based on evidence from recent studies, it can be hypothesized that 123I-MIBG uptake is related to histopathologic changes in the myocardium. METHODS: The relation of 123I-MIBG uptake to the histologic findings for the heart was studied in 24 patients with dilated cardiomyopathy (DCM). The study group did not include patients with complicating disorders that primarily affect the adrenergic nervous system. The 123I-MIBG uptake was visually assigned one of four grades using the two criteria of the mean score for six regional uptake grades (mean score) and the global score obtained by visual evaluation of the entire image (global score). The 123I-MIBG uptake score was also determined for the region at which the biopsy specimen was obtained (biopsy region score). The histologic findings were evaluated by assigning one of four grades for each of the following five factors: myocyte hypertrophy, myocardial fibrotic change, myocyte degeneration and necrosis, mononuclear cell infiltration, and myocyte disarray. The sum for all grades was defined as the total score, and the global score was also assigned to the overall histologic findings. RESULTS: All of the global, mean, and biopsy region scores for 123I-MIBG uptake correlated significantly with the global and total scores for the histologic findings. Among the histologic factors, myocyte degeneration showed score correlated with all global, mean, and biopsy region scores for the uptake. Myocyte hypertrophy was associated weakly with the 123I-MIBG uptake scores. CONCLUSION: These results indicate that 123I-MIBG uptake imaging is associated with histopathologic abnormalities in patients with DCM.

3-Iodobenzylguanidine↗

PubMed1997

Immunomodulatory effects of a plasmid expressing B7-2 on human immunodeficiency virus-1-specific cell-mediated immunity induced by a plasmid encoding the viral antigen.

B7 co-stimulation is essential for activating resting T cells following antigen recognition by the T cell receptor. To determine whether B7 has adjuvant activities on human immunodeficiency virus type-1 (HIV-1)-specific immunity induced by inoculation of a plasmid encoding HIV-1 env and rev (DNA vaccine), B7-1 and B7-2 expression plasmids were co-inoculated with the DNA vaccine. The delayed-type hypersensitivity response and cytotoxic T lymphocyte (CTL) activity were significantly enhanced when B7-2 expression plasmid was co-inoculated with the DNA vaccine, but were unaffected when the B7-1 expression plasmid was used with the vaccine instead. The immunological response enhanced by B7-2 decreased below the level of mice immunized with the DNA vaccine in combination with CTLA4Ig, an inhibitor of the B7/CD28 co-stimulatory signal, suggesting that this signal is critical for the enhanced response induced by co-inoculation of the DNA vaccine and B7-2 expression plasmid. This enhancement appeared to occur via an interferon-gamma (IFN-gamma)-dependent mechanism, as combined administration of the B7-2 plasmid and neutralizing anti-IFN-gamma antibody abrogated the virus-specific cell-mediated immunity. These results suggest that this gene-based co-inoculation strategy using HIV-1 viral antigen and B7-2 co-stimulatory molecule could be a powerful means of combating HIV-1 infection.

AIDS Vaccines↗

PubMed1997

Strong augment effect of IL-12 expression plasmid on the induction of HIV-specific cytotoxic T lymphocyte activity by a peptide vaccine candidate.

We previously reported that repeated inoculation of VC1, a macromolecular multicomponent peptide vaccine emulsified with Freund's adjuvant (VC1-F), induced high cytotoxic T lymphocyte (CTL) levels and a substantial level of multivalent antibodies which neutralized various human immunodeficiency virus type 1 (HIV-1) isolates. In the present study, we report that inoculation of VC1-F plus interleukin (IL)-12 expression plasmid can induce a higher antigen-specific CTL response compared to that with VC1-F alone. VC1-F plus IL-12 expression plasmid or VC1-F alone were inoculated to BALB/c mice twice at interval of 2 weeks. Two weeks after the second inoculation, spleen effector cells from these mice were examined. Stronger CTL responses against target cells were observed from the inoculation of VC1-F plus IL-12 plasmid than from that with VC-1F alone, but there was no difference in antibody induction. The inoculation of VC1 plus IL-12 plasmid also produced higher CTL activity than the inoculation of VC1 alone. These augmented CTL activities were not observed using target cells pulsed with non-HIV-specific peptides and different class I haplotype cells. These data demonstrate that co-inoculation of cell-mediated immune potent antigen and IL-12 plasmids can enhance the antigen-specific CTL response. This may be a potential approach for the induction of cellular immunization against HIV-1 and other diseases.

AIDS Vaccines↗

PubMed1997

Immunohistochemical analysis of intercellular adhesion molecule-1 expression in human gastric adenoma and adenocarcinoma.

In this study, we examined the distribution of intercellular adhesion molecule-1 (ICAM-1) in gastric adenomas and carcinomas immunohistochemically at the light and electron microscopic levels. ICAM-1 was expressed on tumour cells in 12 of 28 gastric carcinomas and in 3 of 11 adenomas but not on most normal gastric epithelial cells. ICAM-1 was localized on luminal sites of neoplastic glands in adenomas and in intestinal-type carcinomas, and rarely on the surface of tumour cells of diffuse carcinomas. Expression of ICAM-1 on the tumour cells was more frequent in intestinal-type than diffuse carcinomas (P < 0.005). At the ultrastructural level, ICAM-1 was present prominently on the apical membrane and weakly on the lateral surface of the tumour cells of the intestinal-type carcinoma and also localized on the perinuclear membrane and the membrane of the endoplasmic reticulum of cancer cells. There was no significant association between ICAM-1 expression and HLA antigen expression or the number of infiltrating lymphocyte subsets. These results may implicate the synthesis of ICAM-1 by gastric cancer cells, but the expression is infrequent and may not be sufficient for host immune surveillance of the tumour cell.

Adenocarcinoma↗

PubMed1997

Mixed connective tissue disease associated with idiopathic portal hypertension and chronic thyroiditis.

We report a patient with mixed connective tissue disease (MCTD) associated with idiopathic portal hypertension (IPH) and chronic thyroiditis. The patient was a 68-year-old Japanese woman who was admitted to our hospital for treatment of bleeding esophageal varices. She had previously exhibited Raynaud's phenomenon and had had arthritis for about 30 years. She also had had high titers anti-U1 of ribonucleoprotein (RNP) anti-single strand-DNA autoantibodies for 2 years, and had been diagnosed with MCTD 1 year previously. The bleeding from esophageal varices was successfully stopped by endoscopic injection sclerotherapy. Results of laboratory examinations, imaging examinations, and laparoscopy, including liver biopsy, indicated that the esophageal varices were caused by portal hypertension due to IPH. The patient also had a diffusely firm and enlarged goiter and hypothyroidism, and she exhibited anti-thyroid microsomal antibodies and anti-thyroglobulin antibodies, she was diagnosed as having a complication of chronic thyroiditis. This association of MCTD, IPH, and chronic thyroiditis is quite rare and provides a unique opportunity to observe immunological involvement in the pathogenesis of IPH.

Aged↗

PubMed1997

Flow cytometry analysis of the Fas ligand expression of activated lymph node T-cells.

There is increasing evidence for the role of the Fas/Fas ligand interaction in the immunoregulation of T-cells. We studied the expression of the Fas ligand (FasL) in activated peripheral T-cell in vitro, and its relation to autonomous cell death by flow cytometry. Following the stimulation of lymph node T-cells with anti-CD3 and rIL2, the mRNA level of FasL increased more than four times during the first 2 days over the level before stimulation. The surface expression of FasL was observed on 27% of the population at day 2 after stimulation and increased to approximately 50% at day 3. Kinetic analysis by flow cytometry, however, indicated that all T-blasts transformed during activation did not express FasL. FasL expression became evident simultaneously with the termination of cell expansion. Since cells remained viable (> 90%) at day 3 as judged by trypan blue-exclusion, cell membranes expressing FasL were supposed to be still intact. Concomitantly with FasL-expression, spontaneous DNA fragmentation was observed. These observations support the idea that autonomous Fas/FasL interaction mediates apoptosis in activated peripheral T-cells as demonstrated in T-cell hybridoma or established T-cells.

Animals↗

PubMed1997

Present status of autoimmune hepatitis in Japan--correlating the characteristics with international criteria in an area with a high rate of HCV infection. Japanese National Study Group of Autoimmune Hepatitis.

BACKGROUND/AIMS: A nationwide survey of autoimmune hepatitis (AIH) was carried out in Japan. METHODS: Four hundred and ninety-six patients were enrolled by questionnaires sent to 101 hospitals with hepatology specialists. RESULTS: The clinical features of Japanese AIH were as follows: most patients were middle-aged women; serum autoantibodies, especially antinuclear antibody, were frequently positive, serum IgG level was high, and HLA-DR4 was the major HLA allotype. Liver-kidney microsomal type 1 antibody was positive in nine of 79 patients tested. Eight of these antibody positive patients were also positive for antinuclear antibody and five for anti-smooth muscle antibody. Ninety-two percent of the patients showed piecemeal necrosis and 60% bridging necrosis; plasma cell infiltration in the portal areas was observed in 50% of the patients. Only 12.3% were diagnosed as having liver cirrhosis. A favorable effect of corticosteroid, normalization of serum transaminases, was observed in 89% of 317 patients, who were treated with an initial dose of over 30 mg/day. Sixty-two patients were positive for hepatitis C virus (HCV) markers. In these patients, however, only one patient was liver-kidney microsomal type 1 antibody positive. Corticosteroid was effective in 30 (81%) of 37 HCV-marker-positive patients treated with this agent. Thus the efficacy of corticosteroid did not differ from that in AIH patients without HCV infection (90%). Similarly, interferon treatment was used in 20 patients, all of whom were positive for HCV-RNA, and resulted in 50% efficacy as determined by normalization of the serum transaminase level 6 months after treatment. The International Diagnostic Scoring System for the diagnosis of AIH worked well in these patients, except for HCV-infected individuals, that is, approximately 10% of the total of AIH patients.

Adolescent↗

PubMed1997

DNA vaccination followed by macromolecular multicomponent peptide vaccination against HIV-1 induces strong antigen-specific immunity.

The induction of a strong and long-lasting immunity characterized by both a humoral and cell-mediated immune (CMI) response is one of the most important considerations in developing an effective HIV vaccine. In previous studies, we have independently developed both DNA vaccine and macromolecular multicomponent peptide vaccine (VC1) candidates. In the present study, we attempted to optimize the vaccination protocol using mice, guinea pigs, rabbits and Macaca fuscata monkeys. Repeated vaccination with VC1 induced a substantial level of multivalent antibodies which neutralized various HIV-1 strains, as determined using a p24 inhibition assay. On the other hand, repeated immunization with DNA vaccine induced and sustained high levels of cytotoxic T lymphocytes (CTLs). In addition, when DNA vaccination was followed by multicomponent peptide vaccination, levels of both humoral immunity and CMI increased, and this effect continued for at least 10 months. These data clearly demonstrate that for inducing HIV-1 specific immunity, immunization with DNA vaccine followed by VC1 boosting produces better results than immunizing with either vaccine alone.

AIDS Vaccines↗

PubMed1997

HIV-1-specific cell-mediated immunity is enhanced by co-inoculation of TCA3 expression plasmid with DNA vaccine.

We developed a candidate DNA vaccine designated pCMV160IIIB with pcREV (pCMV160IIIB/REV) that encodes gp160 of human immunodeficiency virus (HIV)-1IIIB and Rev driven by the cytomegalovirus (CMV) promotor. This vaccine induced both HIV-1-specific antibodies and cytotoxic T lymphocyte (CTL) activity. In the present study, we inoculated the TCA3 expression plasmid into mouse skeletal muscle with pCMV160IIIB/REV to determine whether this cytokine expression plasmid was able to modify the immune response. Results of a delayed-type hypersensitivity (DTH) assay using footpad swelling as well as those of a CTL assay clearly demonstrated that cell-mediated immunity (CMI) elicited by co-inoculation of pCMV160IIIB/REV with the TCA3 expression plasmid was markedly enhanced compared with that obtained using pCMV160IIIB/REV alone. When TCA3 expression plasmid was inoculated with anti-TCA3 antibody, enhancement of the DTH response was suppressed below the level of that obtained with pCMV160IIIB/REV alone. The titre of HIV-1-specific IgG2a was slightly high when pCMV160IIIB/REV was co-inoculated with this plasmid, suggesting that T-helper 1 (Th1) response was predominant in TCA3-inoculated mice. Infiltration of mononuclear cells was seen in the muscles at sites where TCA3 expression plasmid had been inoculated. Our present data suggest that TCA3 expression plasmid has potent adjuvant activity that results in an augmented CMI response.

AIDS Vaccines↗

PubMed1997

Relationship between a low toxicity of the mutant A subunit of enterotoxigenic Escherichia coli enterotoxin and its strong adjuvant action.

In the work described here it was determined if and how unnicking in the A subunit of Escherichia coli enterotoxin at Arg192 or nearby residues affected biological activities of the toxin. The mutant toxin was constructed to lack the nick site in the A subunit by deleting the tripeptide Arg192-Thr193-Ile194, which is essential for toxicity. The mutant toxin did not exhibit agmatine ADP-ribosyltransferase activity in the presence or absence of the ADP-ribosylation factor and had less diarrhoeal activity and lower induction of cyclic AMP than did LT. The mutant toxin exhibited a much stronger adjuvant action on antibody responses to measles virus, keyhole limpt haemocyanin, bovine immunoglobulin and ovalbumin compared with LT. The altered toxicity of the mutant toxin might be closely related to the potent adjuvant action on antibody responses to antigens. The relationship between two activities is discussed.

ADP Ribose Transferases↗

PubMed1997

Accumulation of multiple T-cell clonotypes in the liver of primary biliary cirrhosis.

The histological hallmark of primary biliary cirrhosis (PBC) is the destruction of the interlobular and septal bile ducts accompanied by a dense accumulation of lymphocytes; this constellation of features is termed chronic nonsuppurative destructive cholangitis. To analyze the T cells responsible for bile duct destruction, the T-cell receptor (TCR) Vbeta repertoire was studied in liver biopsy specimens, and also in peripheral blood lymphocytes (PBL) obtained from seven patients with PBC in the early stage (Scheuer's stage I or II). The complementary DNA (cDNA) of each TCR Vbeta1-20 chain was amplified by reverse-transcription polymerase chain reaction (RT-PCR), and the PCR products were examined by single-strand conformation polymorphism (SSCP) analysis. On the RT-PCR/SSCP analysis, a leukemic cell line, HPB-ALL, showed bands in TCR Vbeta 5.2 and Vbeta 6, indicating clonal expansion with distinct TCR. In the PBL from healthy subjects, the PCR products were amplified from many TCR Vbeta and were shown as smears on SSCP, suggesting that PBL consist of diverse T-cell clones. In PBC, many TCR Vbeta products were amplified by RT-PCR in both liver tissues and PBL, and no biased expression of a particular Vbeta was observed. SSCP analysis revealed multiple bands in most Vbeta chains, suggesting the presence of selected but multiple T-cell clones. Both the number and types of Vbeta showing clonal expansion were heterogeneous in the PBC patients. A comparative RT-PCR SSCP analysis of each TCR Vbeta between tissue lymphocytes and PBL revealed the presence of some identical T-cell clones in both the PBC liver and the PBL. These results suggest that T cells infiltrating the liver in PBC consist of multiple clonotypes and that T-cell clones accumulated in the liver are also present in PBL.

Adult↗

PubMed1997

Fibrosarcoma versus cellular fibroma of the ovary: a comparative study of their proliferative activity and chromosome aberrations using MIB-1 immunostaining, DNA flow cytometry, and fluorescence in situ hybridization.

We retrospectively analyzed the proliferative activity and the centromeric copy number of chromosomes 8, 12, and 17 in three cases of fibrosarcoma and eight cases of cellular fibroma of the ovary using MIB-1 immunostaining, DNA flow cytometry, and fluorescence in situ hybridization (FISH) on paraffin-embedded tissue specimens. In our study, both the MIB-1 labeling index (LI) and the proliferative index (% of cells in S + G2 + M phase) in fibrosarcomas were higher than those in cellular fibromas. The FISH analysis demonstrated the sole abnormality of a gain of trisomy 12 cells in all eight cases of cellular fibroma. Both a gain of trisomy 12 cells and a gain of tetrasomy 12 cells were observed in one case of fibrosarcoma. A gain of trisomy 8 cells was observed in all two fibrosarcomas in which signals were detected. By contrast, neither a gain of trisomy 8 cells nor a gain of tetrasomy 12 cells was observed in any of the eight cases of cellular fibroma. Chromosome 17 showed disomy in all eleven cases. On the basis of these findings, a gain of trisomy 8 cells is therefore considered to be an adequately effective marker to distinguish between cellular fibroma and fibrosarcoma of the ovary, and it may also be related to the proliferative activity of fibrosarcoma of the ovary.

Adolescent↗

PubMed1997

Fixed drug eruption caused by iopamidol, a contrast medium.

We report a patient who developed a fixed drug eruption caused by the contrast medium, Iopamidol. We diagnosed it by her episode pattern and the results of patch tests. This substance has not been previously implicated as a cause of fixed drug eruption. Immunohistochemical studies showed Fas expression in keratinocytes of the lesion, but not in the uninvolved skin. This finding may explain the preferential localization of fixed drug eruption.

Adult↗

PubMed1997

Ulcerative lichen planus: a rare variant of lichen planus.

A 54-year-old Japanese man with ulcerative lichen planus is reported. He had a painful erythema with ulcers on his soles and nail dystrophy. Mucous involvement was present on his lip. His hairs were intact. Histopathological findings confirmed the diagnosis of lichen planus.

Erythema↗

PubMed1997

Perianal Paget's disease years after rectal adenocarcinoma removal.

BACKGROUND: Perianal Paget's disease often coincides with anorectal carcinoma, which extends into the epidermis from a contiguous organ. OBJECTIVE: Our purpose was to present a patient with perianal Paget's disease who had a rectal adenocarcinoma excised 14 years previously in another hospital and to determine whether there is a relationship between the perianal Paget's disease and the rectal adenocarcinoma. METHODS: We examined the resected specimens of the rectal adenocarcinoma and the perianal Paget's disease histologically. RESULTS: In the resected specimen of the rectal adenocarcinoma, Paget cells were present within the anal epidermis adjacent to the rectal adenocarcinoma. The Paget cells showed the same histochemical and immunohistological findings as the adenocarcinoma cells. CONCLUSION: There was a close relationship between the perianal Paget's disease and the rectal adenocarcinoma. It is probable that the Paget cells were derived from direct spread from the rectal adenocarcinoma.

Adenocarcinoma↗

PubMed1997

Keratoacanthoma and squamous cell carcinoma: study of PCNA and Le(Y) expression.

To determine whether keratoacanthoma (KA) is unique or a variant of squamous cell carcinoma (SCC), the expressions of proliferating cell nuclear antigen (PCNA) and Le(Y) in 16 KA cases (11 fully developed and 5 involutional types; two of the involutional types transformed from the fully developed types) and 11 cases of well-differentiated SCC were investigated by immunohistochemistry. The monoclonal antibodies used were PC-10 for PCNA and BM-1/JIMRO for Le(Y). Le(Y) is one of the Lewis-type antigens, and is thought to be related to apoptosis. In most of the cases of fully developed KA, the PCNA expression was linear or band-like and was limited to the basal and suprabasal layers, while the Le(Y) expression was seen in a diffuse pattern throughout the epidermis, except for the basal layer. However, in 5 of these cases, there were some areas in the basal and suprabasal layer where PCNA-positive cells were few, while Le(Y) expression was very strong. In the involutional Ka cases, the PCNA expression was very weak in the basal and suprabasal layers, and the Le(Y) expression was strong throughout the epidermis. In the SCC cases, the PCNA and Le(Y) expressions were very strong and diffuse throughout the tumor masses except for the lack of PCNA in the horny layer and the lack of Le(Y) in the basal layer. These findings indicate that there are some differences between KA and SCC in the expression pattern of PCNA and Le(Y), and that apoptosis may occur in the Le(Y)-positive areas in the basal and suprabasal layers and thus cause the involution of KA.

Aged↗

PubMed1997

Monophosphoryl lipid A enhances both humoral and cell-mediated immune responses to DNA vaccination against human immunodeficiency virus type 1.

To enhance immunity induced by DNA vaccination against human immunodeficiency virus type 1 (HIV-1), we evaluated the efficacy of monophosphoryl lipid A (MPL), an adjuvant of bacterial origin. BALB/c mice were intramuscularly injected with immunogenic DNA, encoding the env and rev genes of the HIV-1(IIIB) strain, formulated with MPL dissolved in different vehicles (MPL in stable emulsion and MPL in aqueous formulation). The sera from mice immunized with the two preparations of MPL revealed 2(6) to 2(9) times higher HIV-1-specific immunoglobulin G (IgG) titers than the sera from mice immunized without MPL. In virus neutralization tests for HIV-1(IIIB), by p24 assay and antifusion assay of infected MOLT-4 cells, MPL tends to elicit antibody more protective than antibody elicited without adjuvant. MPL also elicited stronger delayed-type hypersensitivity and cytotoxic-T-lymphocyte activity against HIV-1(IIIB) compared to DNA alone. HIV-1-specific IgG subclass analysis showed that MPL tends to facilitate IgG2a production, suggesting enhancement of a predominant T-helper-type-1 response, and this enhancement may help to facilitate protective-antibody induction. Furthermore, a chloramphenicol acetyltransferase (CAT) assay was employed to determine whether MPL affected the gene expression process. Interestingly, both MPL preparations reduced CAT activity in the muscle injected with CAT expression vector but increased anti-CAT antibody production. These results indicate that MPL acts as an effective adjuvant for immunogenic DNA injection despite reduced expression of encoding protein in muscle. We conclude that MPL has a strong adjuvant effect on DNA vaccination against HIV-1.

AIDS Vaccines↗