Successful xeno long-term cryopreserved fetal liver fragment transplantation from pig to rat or beagle omentum using immunocapsule.
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Animals↗
Biomedical subjects
K Tsuji
Publications and source records attributed to K Tsuji.
Studies of xeno tissue typing: xeno MLR and Southern blotting using HLA, C4A, Bf, and SLA cDNA probes and TCRV-beta clonotyping.
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Animals↗
Can fetal xeno whole-organ (heart, lung, kidney, and liver) grafts escape from hyperacute rejection in experimental discordant combinations as compared with adult xenografts?
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Acute Disease↗
Protection by diphenyliodonium against glutamate neurotoxicity due to blocking of N-methyl-D-aspartate receptors.
The protective effect of diphenyliodonium, known as an inhibitor of flavin enzymes including nitric oxide synthases, was examined against the neurotoxicity of excitatory amino acids on cultured spinal neurons of the rat. Diphenyliodonium reduced the neuronal damage induced by 15-min exposure to glutamate or N-methyl-D-aspartate in a dose-dependent manner; half effective concentrations (EC50) were about 3 microM for both. Protection was only observed when diphenyliodonium was added into the exposure medium. Diphenyliodonium showed no effect on the toxicity induced by 24 h exposure to non-N-methyl-D-aspartate receptor agonists. Using a microfluorometry technique with Fura 2, we observed that diphenyliodonium reversibly inhibited the N-methyl-D-aspartate-evoked intracellular Ca2+ elevation. The amount of 45Ca2+ influx induced by N-methyl-D-aspartate was also inhibited by diphenyliodonium in a dose-dependent manner; EC50 was about 3 microM. Furthermore, we examined the effect of diphenyliodonium on an opening activity of the N-methyl-D-aspartate receptors estimated by binding of dizocilpine maleate to membrane fractions from whole brain of adult rat and from cultured spinal neurons. Diphenyliodonium inhibited the binding of dizocilpine maleate dose-dependently; EC50 was 5-8 microM. These results suggest that diphenyliodonium is a new antagonist to the N-methyl-D-aspartate receptors and that diphenyliodonium protects neurons against glutamate toxicity due to a direct blocking of the Ca2+ influx. This conclusion is supported by the similarity of the stereochemical structures predicted by computer between diphenyliodonium and dizocilpine maleate.
Animals↗
Serum soluble human leucocyte antigen class I in paediatric liver transplantation with live, related donors.
Serum soluble human leucocyte antigen (HLA) class-I is a useful marker for predicting immunological events in organ transplantation. In cadaver liver transplant cases it is especially the case that high amounts of soluble HLA-I are excreted from the grafts. In Japan, almost all liver transplants have been performed from living parent donors to their children. Therefore, it is interesting to know how soluble HLA-I changes in relation to clinical course. As part of this study we first examined serum concentrations of soluble HLA-I in 33 paediatric patients using enzyme-linked immunosorbent assay. Soluble HLA-I is composed of three different sized molecules (45, 39 and 34-36 kDa); then the change of distribution of these three molecules was demonstrated by Western blot analysis. When donor and recipient have different soluble HLA-I band patterns, the origin of the antigen can be assumed by this method. We found that in a comparison between pre- and post-transplants, the six out of eight (75%) patients that suffered episodes of acute rejection showed a significant elevation of soluble HLA-I, and all patients with infectious episodes had an elevated soluble HLA-I. Meanwhile, 10 out of 22 (45%) patients without any clinical complications still showed increased soluble HLA-I. The Western blot analysis showed that the soluble HLA-I molecules were considerably derived from the grafted liver, from one week to 24 months after grafting. In acute rejection, the band signals of donor origin were significantly increased. These signals were attenuated after immunosuppressive therapy. The grafted liver appears to contribute to the increase of soluble HLA-I following liver transplantation, and this increase is greater with the effects of the host immune system.
Adolescent↗
The role of mel-18, a mammalian Polycomb group gene, during IL-7-dependent proliferation of lymphocyte precursors.
mel-18 is a mammalian homolog of Drosophila melanogaster Polycomb group genes. Mice lacking the mel-18 gene show a posterior transformation of the axial skeleton, severe combined immunodeficiency, and a food-passing disturbance in the lower intestine due to hypertrophy of the smooth muscle layer. In this study, the severe combined immunodeficiency observed in mel-18 mutant mice is correlated with the impaired mitotic response of lymphocyte precursors upon interleukin-7 stimulation. Strikingly, the axial skeleton and lymphoid phenotypes are identical in both mel-18 and bmi-1 mutants, indicating that the Mel-18 and Bmi-1 gene products might act in the same genetic cascade. These results suggest that mammalian Polycomb group gene products are involved in cell cycle progression in the immune system.
Animals↗
Isolation and chemical-structural determination of a novel aromatic amine mutagen in water from the Nishitakase River in Kyoto.
Water samples from the Nishitakase River in Kyoto, Japan, especially taken at sites below sewage plants, show significantly high mutagenicity in the Ames test. In the present study, mutagens in the river water were adsorbed to 24 g of blue rayon, extracted, and separated by HPLC on ODS columns. Five mutagenic compounds (I-V) were isolated, and they accounted for 21%, 17%, 11%, 12%, and 6%, respectively, of the total mutagenicity of the blue rayon-adsorbed materials. With compound I obtained from adsorbate to 24 g of blue rayon as a marker, a large quantity (1.1 mg) of mutagenic compound I was isolated by Sephadex LH-20 column chromatography and HPLC on ODS columns from material adsorbed to 27 kg of blue cotton. X-ray crystal analysis was carried out with the debrominated derivative of compound I. Based on this X-ray crystallography data and the UV, mass, and 1H-NMR spectra of both the derivative and compound I, the structure of compound I was determined to be 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]-5-amino - 7-bromo-4-chloro-2H-benzotriazole (PBTA-1). PBTA-1 is a newly identified potent mutagen, inducing 1,200,000 revertants of Salmonella typhimurium YG1024 per microgram in the presence of S9 mix.
Amines↗
Thrombopoietin alone stimulates the early proliferation and survival of human erythroid, myeloid and multipotential progenitors in serum-free culture.
We examined the effects of recombinant human thrombopoietin (TPO, c-Mpl ligand) on the proliferation and differentiation of human haemopoietic progenitors other than megakaryocytic progenitors using serum-free cultures. TPO alone supported the generation of not only megakaryocytic (MK) but also blast cell (blast) colonies from cord blood CD34+ cells. Delayed addition of a cytokine cocktail (cytokines; interleukin (IL)-3, IL-6, stem cell factor, erythropoietin, granulocyte-macrophage colony-stimulating factor, and TPO) to cultures with TPO alone on day 7 induced various colonies including granulocyte-macrophage (GM) colonies, erythroid bursts (E), granulocyte-erythrocyte-macrophage-megakaryocyte (GEMM) colonies. Replating experiments of blast colonies supported by TPO alone for culture with cytokines revealed that approximately 60% of the blast colonies contained various haemopoietic progenitors. Single cell cultures of clone-sorted CD34+ cells indicated that TPO supported the early proliferation and/or survival of both primitive and committed haemopoietic progenitors. In serum-free suspension cultures, TPO alone significantly stimulated the production of progenitors for MK, GM, E and GEMM colonies as well as long-term culture-initiating cells. These effects were completely abrogated by anti-TPO antibody. These results suggest that TPO is an important cytokine in the early proliferation of human primitive as well as committed haemopoietic progenitors, and in the ex vivo manipulation of human haemopoietic progenitors.
Antigens, CD34↗
Thrombopoietin-independent effect of interferon-gamma on the proliferation of human megakaryocyte progenitors.
Flow cytometric study revealed that almost all CD34+ cells in human umbilical cord blood expressed interferon-gamma receptor (IFN-gammaR). To clarify the precise functional roles of IFN-gammaR in human CD34+ cells, we examined the effect of IFN-gamma alone and in combination with various cytokines on the growth of haemopoietic progenitor cells in CD34+ cells using a serum-free clonal culture. Surprisingly, IFN-gamma alone supported only megakaryocyte (MK) colonies in a dose-dependent manner with a plateau level at 1000 U/ml of IFN-gamma. IFN-gamma at 1000 U/ml induced 10 +/- 1.2 MK colonies from 1 x 10(3) CD34+ cells, whereas thrombopoietin (TPO), interleukin (IL)-3, stem cell factor (SCF) or IL-6 alone induced 22 +/- 4.0, 22 +/- 4.2, 4 +/- 0.6 and 0 MK colonies, respectively. The addition of anti-IFN-gamma monoclonal antibody (mAb) to the IFN-gamma culture completely abrogated MK colony formation, whereas the mAb had no effect on TPO-dependent production of MK colonies. In contrast, although anti-TPO polyclonal Ab almost completely blocked TPO-dependent MK colony formation, it failed to inhibit the generation of MK colonies induced by IFN-gamma, suggesting that the observed effect of IFN-gamma on the proliferation of human MK progenitor cells is independent of TPO. The addition of IFN-gamma to culture with TPO or SCF significantly augmented the development of MK colonies, whereas it did not affect IL-3-dependent MK colony formation. Additionally, IFN-gamma induced the increase of DNA content of cultured glycoprotein IIb/IIIa-positive megakaryocytes. These results suggest that IFN-gamma may have regulatory roles in human megakaryocytopoiesis.
Antibodies, Monoclonal↗
Defective response to thrombopoietin and impaired expression of c-mpl mRNA of bone marrow cells in congenital amegakaryocytic thrombocytopenia.
Congenital amegakaryocytic thrombocytopenia (CAMT) is an uncommon disorder in newborns and infants, characterized by isolated thrombocytopenia and megakaryocytopenia in the first year without physical anomalies. The defect of thrombopoiesis is not well understood. Recently, thrombopoietin (TPO), the ligand for the c-mpl receptor, was cloned. Accumulating evidence from in vitro and in vivo studies indicate that TPO plays a key role in the regulation of megakaryocytopoiesis. In this study we examined the effect of TPO on megakaryocyte colony formation from a patient with CAMT using a plasma-containing methylcellulose clonal culture. The in vitro results demonstrated a defective response to TPO in megakaryocyte colony formation from bone marrow mononuclear cells (MNC) of the patient. although interleukin-3 (IL-3) but not stem cell factor (SCF) induced only a small number of megakaryocyte colonies. These findings indicated that thrombocytopenia in CAMT could not be corrected by administration of TPO in vitro. Additionally, clonal cultures containing SCF, IL-3, IL-6 and erythropoietin showed decreased numbers of erythroid and myelocytic progenitors in the bone marrow of the patient. The serum TPO level measured by enzyme-linked immunosorbent assay was significantly higher than that in healthy controls. By PCR, marrow MNC from healthy children and from a patient with essential thrombocytosis expressed c-mpl mRNA, whereas no c-mpl mRNA was detected in marrow MNC from the patient with CAMT. There was no difference in the CD34 expression and c-kit mRNA between the CAMT patient and healthy children. The results of this study suggest that the pathophysiology in CAMT may be a defective response to TPO in haemopoietic cells through impaired expression of c-mpl mRNA.
Bone Marrow↗
Translocation breakpoint maps 5 kb 3' from TWIST in a patient affected with Saethre-Chotzen syndrome.
Saethre-Chotzen syndrome, a common autosomal dominant craniosynostosis in humans, is characterized by brachydactyly, soft tissue syndactyly and facial dysmorphism including ptosis, facial asymmetry, and prominent ear crura. Previously, we identified a yeast artificial chromosome that encompassed the breakpoint of an apparently balanced t(6;7) (q16.2;p15.3) translocation associated with a mild form of Saethre-Chotzen syndrome. We now describe, at the DNA sequence level, the region on chromosome 7 affected by this translocation event. The rearrangement occurred approximately 5 kb 3' of the human TWIST locus and deleted 518 bp of chromosome 7. The TWIST gene codes for a transcription factor containing a basic helix-loop-helix (b-HLH) motif and has recently been described as a candidate gene for Saethre-Chotzen syndrome, based on the detection of mutations within the coding region. Potential exon sequences flanking the chromosome 7 translocation breakpoint did not hit known genes in database searches. The chromosome rearrangement downstream of TWIST is compatible with the notion that this is a Saethre-Chotzen syndrome gene and implies loss of function of one allele by a positional effect as a possible mechanism of mutation to evoke the syndrome.
Acrocephalosyndactylia↗
Molecular analysis of HLA polymorphism in Khoton-Mongolians.
We have investigated polymorphism of the HLA class I and class II genes in Mongolians for the first time using PCR-based techniques. A minor population of Khoton-Mongolians was studied and compared to the major Khalkh-Mongolian population. Eighty-five Khoton- and 41 Khalkh-Mongolian samples were analyzed for polymorphism in HLA-A, -B, -DRB1, -DRB3, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1 loci using PCR-SSOP and PCR-RFLP methods. Allele and haplotype frequencies were calculated. The results were then compared to those obtained from other human populations. In Khoton-Mongolians, the frequency of HLA-B38, DRB1*0301, DQA1*0502, DQB1*0201 and DPB1*0401 were significantly higher than those in other Mongoloid populations including Khalkh-Mongolians, Buryat, Chinese, Northern Han, Southern Han, Koreans and Japanese. In contrast, the frequency of HLA-A2, DQA1*0102, DPB1*0201 and DPB1*0501 were significantly lower in Khoton-Mongolians. Haplotype frequency analysis revealed that Khoton-Mongolians shared the same haplotypes specific to Mongoloids as well as to Caucasoids. On the other hand, several haplotypes were found to be specific for the Khoton. The phylogenetic tree analysis constructed by the NJ method based on allele frequencies of HLA-A, -B, -DRB1, -DQA1, and -DQB1 genes revealed that the Khoton belong to the Northeast Asian cluster and are most closely related to the Khalkh, Inner Mongolian, Uygur and Buryat populations. These data suggest a unique genetic background for Khoton-Mongolians. Furthermore, they are closely related genetically to both Mongoloids and Caucasoids.
Alleles↗
Studies on anti-inflammatory agents. V. Synthesis and pharmacological properties of 3-(difluoromethyl)-1-(4-methoxyphenyl)-5- [4-(methylsulfinyl)phenyl]pyrazole and related compounds.
A series of novel 1,5-diphenylpyrazole derivatives bearing hydrophilic substituents was prepared. The anti-inflammatory and analgesic activities of these compounds were evaluated by using the adjuvant arthritis and Randall-Selitto assays in rats, and the structure-activity relationships were studied. The optimal compound was 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyraz ole (10) with oral ED50 values of 0.31 and 2.6 mg/kg on adjuvant-induced arthritis and carrageenin-induced foot edema, respectively. Compound 10 showed analgesic activities not only toward inflamed paw but also toward normal paw (ED30 = 0.55 and 1.8 mg/kg, respectively) in the Randall-Selitto assay, and moreover, 10 was effective in the tail-pinch assay (ED50 = 21 mg/kg) similarly to morphine. The asymmetric synthesis and pharmacological properties of the enantiomers of 10 are also reported.
Animals↗
Studies on anti-inflammatory agents. IV. Synthesis and pharmacological properties of 1,5-diarylpyrazoles and related derivatives.
A series of novel 1,5-diarylpyrazole derivatives was synthesized and tested for anti-inflammatory and analgesic activities to develop anti-inflammatory agents with fewer side effects than existing nonsteroidal anti-inflammatory drugs. The structure-activity relationships in this series were extensively studied. Electron-withdrawing substituents such as CN and CF3 were optimal at the 3-position of the pyrazole ring. Replacement of these substituents with bulky ones gave less active compounds. The 4-(methylsulfonyl)phenyl group seemed to be the optimal group at the 5-position of the pyrazole ring. The most potent compound was 1-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-pyrazole-3-carbonitrile (19a), with oral ED50 value of 0.030 and 0.47 mg/kg on adjuvant-induced arthritis and collagen-induced arthritis, respectively, and an ED30 value of 7.4 mg/kg in the yeast-induced hyperalgesia (Randall-Selitto) assay. Compound 19a also showed potent inducible cyclooxygenase (COX-2)-inhibitory activity (IC50 = 0.24 microM) with no COX-1 inhibition even at 100 microM.
Anilides↗
Adenoid cystic carcinoma of the external auditory canal: correlation between histological features and MRI appearances.
A rare case of adenoid cystic carcinoma of the external auditory canal with magnetic resonance imaging appearances is reported. Both T1 weighted and T2 weighted MR images showed the tumour as a hypointense mass, although there was marked contrast enhancement. Microscopic examination of the resected tumour showed a preponderance of solid tumour cell nests. According to previous reports, these pathological and radiological findings indicate a poor prognosis.
Aged↗
[Coronary artery bypass grafting using arterial grafts in a patient with rheumatoid arthritis requiring steroid therapy].
We report a 58-year-old man with rheumatoid arthritis (RA) who underwent successful coronary artery bypass grafting (CABG) for stable angina after myocardial infarction. He had been receiving prednisolone for 9 years. Selective coronary angiography revealed 99% stenosis in the left anterior descending branch (LAD; seg. 6). Before going on cardiopulmonary bypass, the inferior epigastric artery (IEA) was anastomosed to the left internal thoracic artery (LITA) in end-to-side fashion. The LITA was anastomosed to LAD (seg. 7) and the IEA was anastomosed to the first diagonal branch (seg. 9). The postoperative course was uneventful and postoperative angiography showed both grafts were well patent. He is now doing well with no angina attack. The stumps of the LITA and IEA were examined pathologically with the atherosclerotic changes of both grafts relatively mild. We consider the arterial grafts are useful for CABG even in the patient with RA requiring steroid therapy.
Angina Pectoris↗
Clinical importance of interleukin-2 receptor alpha-chain expression in acute leukemia. The Japan Cooperative Group of Leukemia/Lymphoma.
To clarify the clinical importance of interleukin-2 (IL-2) receptor (IL-2R) expression in acute leukemia, we examined 517 adult patients with acute leukemia and CML blast crisis (CML-BC). IL-2R alpha was expressed in 42/311 AML, 5/11 acute unclassified leukemia, 24/116 pre-B ALL, 2/32 T-ALL, and 27/47 CML-BC, while IL-2R beta was expressed only in 2 T-ALL. Expression of IL-2R alpha was closely associated with that of different lineage markers, CD11b, CD34, and Ph1+ abnormality. IL-2R alpha(+) non-T leukemic cells did not respond to IL-2. Clinical outcome of IL-2R alpha (+) leukemia showed lower response to conventional chemotherapy and poorer prognosis than IL-2R alpha (-) cases. Serum IL-2R alpha level in IL-2R alpha (+) cases increased at the onset. Our findings indicate the diagnostic importance of IL-2R alpha expression in acute leukemia as a prognostic risk factor with a close relation to the particular cellular characteristics.
Acute Disease↗
[Successful 5'-DFUR, CDDP and MMC combination therapy and 5'-DFUR and carboplatin combination therapy for a patient with inoperable advanced gastric cancer with peritonitis carcinomatosa].
A 71-year-old man with Borrmann type 3 gastric cancer and peritonitis carcinomatosa was treated with 5'-DFUR 600 mg/body p.o. daily, CDDP 50-80 mg/m2 i.v. on day 1 and MMC 6 mg/m2 i.v. on day 2 after intraperitoneal injection of CDDP and OK-432. The cycle of CDDP and MMC was repeated every 4 or 5 weeks. After 15 cycles of treatment, the primary gastric lesion disappeared and regional lymph node metastasis was reduced. Because of relapsing of the original lesion and concomitant renal dysfunction, a changed regimen of CDDP and Carboplatin was tried. Then the gastric lesion was reduced and lymph node metastasis disappeared. The patient has lived for about 3 years after diagnosis, but his gastric lesion is gradually worsening with duodenal invasion. This case indicates that these combination chemotherapies are quite promising as an effective treatment for advanced gastric cancer and good quality of patient's life.
Aged↗