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Biomedical subjects

K Tsuji

Publications and source records attributed to K Tsuji.

At least 271 records · Page 15Linked to original sources
PubMed1996

Xenogeneic iso-skin graft and mixed lymphocyte reaction studies using HLA-DP transgenic mice.

To elucidate the cellular responses against xeno-MHC antigens, in vitro mixed lymphocyte culture (MLC) and in vivo skin grafting (SG) studies were conducted using HLA-DP transgenic mice (B6-DP mice). Xenogenic iso-(B6-DP to B6 mice) MLC showed positive but much lower responses compared to allo-MLC responses. Nevertheless, B6-DP skin grafts were rejected in a similar time course as allo-skin grafts. To examine mechanisms underlining skin graft rejection, both in vitro cytotoxic lymphocyte (CTL) responses and delayed-type hypersensitivity (DTH) reactions were tested. The studies showed that DTH but not CTL reactions were involved for the graft rejection. SG was again conducted after the administration of anti-CD4 and/or CD8 monoclonal antibody (mAb). Mice treated with both CD4 and CD8 mAb accepted B6-DP SG for as long as up to 60 days and those treated with either CD4 or CD8 mAb alone rejected skin grafts on its own most of the time (75% in anti-CD4 mAb treated mice, 88.9% in anti-CD8 mAb treated mice), which suggests that the strict T cell restrictions for xeno-DP antigens do not exist. Even in these finally rejected cases, longer median survival time and final rejection time were observed, and in the other mice (25% in anti-CD4 mAb treated, and 11.1% in anti-CD8 mAb treated mice), graft acceptance was found. Therefore, it was suggested that the immunological reactions leading to the graft rejection occurs most efficiently when both T cell subsets are present. The above results indicate that xenogeneic HLA-DP antigens could act as significant transplantation antigens equivalent to alloantigens despite their lower stimulative activity in vitro, and also support the interpretation that DP antigens act like a minor histocompatibility antigen beyond the difference of species. Monomorphic anti-HLA class II antibodies were detected in recipients' sera as early as 2 weeks and even at 6 months, indicating that xeno-MHC antigens are prone to be memorized to B cells. It was concluded that HLA transgenic mice are useful for the investigation of cellular responses across xeno-MHC barriers.

Animals↗
PubMed1996

Synthesis and structure-activity relationships of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3' or C-7 catechol or related aromatics.

A series of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3' catechol-containing (pyridinium-4-thio)methyl groups and 2-isocephems with C-7 catechol related aromatics have been prepared and evaluated for antimicrobial activity. It turns out that these compounds have highly potent activity against Gram-negative bacteria, especially resistant pathogens such as Pseudomonas aeruginosa. The most active compound of the series was (6S,7S)-7-[2-(2-aminothiazol-4-yl)-2-[(Z)-[(1,5-dihydroxy-4-pyr idon-2-yl) methoxy]imino]acetamido]-3-[[[(4-methyl-5-carboxymethyl)thiazol-2- yl] thio]methyl]-8-oxo-1-aza-4-thiabicyclo [4.2.0] oct-2-ene-2-carboxylic acid which exhibited potent in vitro activity against clinically isolated P, aeruginosa and Acinetobacter baumanii which is also resistant to many anti-infectives, and good in vivo efficacy against clinically isolated P aeruginosa.

Animals↗
PubMed1996

Characterization of peripheral blood progenitor cells (PBPC) mobilized by filgrastim (rHuG-CSF) in normal volunteers: dose-effect relationship for filgrastim with the character of mobilized PBPC.

Filgrastim (rHuG-CSF)-mobilized peripheral blood progenitor cells (PBPC) in healthy Japanese volunteers were characterized in detail using two clonal cell culture systems and double-colour flow cytometry to detect multilineage colony-forming cells and subsets of CD34+ cells. The kinetics of PBPC during the administration of filgrastim was studied, and possible differences in the character of progenitor cells relative to given doses of filgrastim were investigated. Filgrastim was administered subcutaneously to normal volunteers for 7 d at doses of 100, 200 or 400 microgram/m2 (10 per cohort). Treatment with 100 or 200 microgram/m2 filgrastim was well tolerated; however, the 400 microgram/m2 dose level was not completed because of bone pain and myalgia. The treatment strikingly mobilized various types of progenitor cells, including highly proliferative megakaryocytic colony-forming cells. The number of progenitor cells peaked on days 5 and 6. The fold increase of circulating progenitor cells from the baseline value in the volunteers treated with 200 microgram/m2 filgrastim was more pronounced than in those treated with 100 microgram/m2. Treatment with 200 microgram/m2 also released the less mature progenitor cells (i.e. mixed colony-forming cells CD34+/33- cells, and CD34+/HLA-DR-cells) into circulation better than the 100 microgram/m2 dose. These results suggest that daily subcutaneous injection with 200 microgram/m/2 filgrastim for 5 d will effectively mobilize, both qualitatively and quantitatively, PBPC in healthy donors.

Adult↗
PubMed1996

Expression of MAGE genes in human colorectal carcinoma.

OBJECTIVE: The human genes MAGE-1 and -3 encode tumor-specific peptide antigens, which are recognized by autologous cytotoxic T lymphocytes. The antigens coded by those genes may be useful for cancer immunotherapy. There is, however, little information on the expression of these genes in human colorectal carcinomas. METHOD: The expression of MAGE-1, -2, and -3 genes in 54 pairs of tumor and corresponding normal tissue specimens of the colorectum was determined by means of reverse transcription polymerase chain reaction. The induction of MAGE-1, -2, -3, and -4 gene expression in eight colorectal carcinoma cell lines also was examined by use of a demethylating agent, 5-Aza-2'-deoxycytidine (DAC). RESULTS: The expression of MAGE genes was not recognized in normal colorectal tissues at all. In tumor tissue specimens, the expression of MAGE-1, -2, and -3 was recognized in 16 (30%), 15 (28%), and 11 (20%) patients, respectively. The expression was seen frequently in patients with liver metastasis (p < 0.01). Although MAGE-1 or -3 genes were not induced by DAC, MAGE-2 or -4 genes were induced in three of four MAGE-2 negative cell lines or three of seven MAGE-4 negative cell lines, respectively. CONCLUSIONS: The MAGE genes were expressed exclusively in tumor tissues of one third of patients with colorectal carcinoma. The identification of such tumor rejection antigens is considered to uncover a new possibility for the specific immunotherapy of colorectal carcinoma. The demethylating agent may increase the number of patients who might be candidates for MAGE-specific immunotherapy.

Antigens, Neoplasm↗
PubMed1996

Antirheumatic agents. I. Novel methotrexate derivatives bearing an indoline moiety.

Various novel methotrexate (MTX) derivatives bearing an indoline moiety were synthesized and tested for biological activities using human peripheral blood mononuclear cell (hPBMC) and human synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds having potent activity in vitro were further evaluated using an adjuvant arthritis model in vivo. N-[1-(2,4-Diamino-6-pteridinylmethyl)indoline-5-carbonyl]-L-glutam ic acid 2f showed more potent activities than MTX in vitro and in vivo, and N-[1-(2,4-diamino-6-pteridinylmethyl)-indoline-5-carbonyl]-L-2-ami noadipic acid 2d exhibited fairly good activities in vitro and considerable activity in vivo. Compound 2d was, as expected, not sensitive to folyl-polyglutamate synthetase (FPGS) and did not undergo polyglutamation, a process which may be responsible for a side-effect during MTX therapy.

Animals↗
PubMed1996

Antirheumatic agents. II. Novel methotrexate derivatives bearing an alkyl-substituted benzene ring.

Novel methotrexate (MTX) derivatives with either a mono- or dialkyl-substituted benzene ring were synthesized and initially tested for in vitro anti-proliferative activities using human peripheral blood mononuclear cells (hPBMC) derived from healthy volunteers and synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds with potent activities were further evaluated in an in vivo adjuvant arthritis model. In comparison with MTX, a glutamate derivative 3a was more potent as a suppressor of the in vitro cell proliferation and the in vivo experimental arthritis, and a homoglutamate derivative, 3e, exhibited fairly good activities in vitro and considerable activity in vivo in a dose-dependent manner. As expected, 3e did not act as a substrate of folylpolyglutamate synthetase (FPGS), and thus did not undergo polyglutamation, which is thought to be responsible for side-effects that occur during MTX therapy.

Antirheumatic Agents↗
PubMed1996

Isolation of inhibitors of TPA-induced mouse ear edema from Hoelen, Poria cocos.

Triterpene carboxylic acids were isolated from the methanol extract of Hoelen, Poria cocos, and found to inhibit 12-O-tetradecanoylphorbol 13-acetate (TAP)-induced mouse ear edema. Their chemical structures were identified as 3 beta,-16 alpha-dihydroxylanosta-7,9(11),24-trien-21-oic acid, 16 alpha-hydroxydehydropachymic acid, 16 alpha-hydroxytrametenolic acid and dehydrotumulosic acid.

Animals↗
PubMed1996

Changes in body weight and organ weight of Ishibashi (IS) rats with growth.

Changes in body weight (25-175 days old, every 10 days) and weights of various organs (70, 105, 140 and 175 days old), i.e., cerebrum, cerebellum, pituitary gland, thyroid gland, thymus, heart, liver, spleen, adrenal gland, kidney, seminal vesicle, prostate, epididymis, testes, bulbourethral gland and ovary, of Ishibashi (IS) rats with growth, which are model animals for congenital vertebral malformation (spontaneous kyphoscoliosis) were examined as compared with Brown Norway (BN) rats, which are genetically irrelevant to IS rats, and also with hybrid rats (IBF, rats) which are between IS and BN rats. The experimental results showed that body weight and weights of various organs except cerebrum, cerebellum and thymus were greater in IS rats than in BN rats, and body weight and weights of various organs of IBF, rats were intermediate between the two strains of rats.

Animals↗
PubMed1996

Aberrant growth of granulocyte-macrophage progenitors in juvenile chronic myelogenous leukemia in serum-free culture.

We investigated the properties of granulocyte-macrophage (GM) progenitors obtained from patients with juvenile chronic myelogenous leukemia (JCML). CD34+ bone marrow cells from a patient with JCML, unlike normal bone marrow cells, generated a large number of cells in serum-containing liquid culture without additional hematopoietic factors. In serum-deprived culture, only granulocyte colony-stimulating factor (G-CSF) had a modest stimulatory effect on GM colony growth in normal controls. In contrast, stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3), as well as G-CSF, when tested individually, generated significant numbers of GM colonies in some JCML patients. All two-factor combinations generated significantly more GM colonies in JCML compared with normal controls. In particular, GM-CSF plus SCF exerted an interaction equivalent to the all-factor combination in most patients. Significant differences in the size and constituent cells of GM colonies stimulated by GM-CSF plus SCF were also observed. These results suggest that one possible mechanism for the excessive cell production in JCML is the strong proliferation of GM progenitors induced by hematopoietic factors, especially SCF. According to immunofluorescent analysis, however, it is unlikely that this multiplication is due to an increase in the cell surface expression of c-kit receptors on JCML progenitors.

Antigens, CD34↗