Biomedical subjects
Publications and source records attributed to Kenji Matsumoto.
We present a two-well Hamiltonian system in which isotropic random perturbation induces non-ergodic behavior where orbits tend to spend more time in one of two wells. It is numerically shown that this behavior is due to the difference in its orbital separation rates near the exits of wells.
Arsenic trioxide, As(2)O(3) (ATO), has been established to be an effective agent for treating acute promyelocytic leukemia, but its effect on solid tumors has not been fully explored. In the present study in a murine xenograft system, we found that ATO significantly inhibited tumor growth of the inoculated human hepatocellular carcinoma cell line HuH7 when administered either intravenously or intratumorally. Pathological examination revealed that ATO induced extensive cell death in the tumor. Some of the dead cells in intratumorally ATO-treated mice showed characteristic features of apoptosis, such as nuclear condensation and fragmentation, and were TUNEL-positive. The measurement of arsenic by using particle induced X-ray emission revealed that arsenic was accumulated more in the tumor than in brain, kidney or liver after the intravenous injection of ATO, which is consistent with the hemorrhagic cell death observed in ATO-treated tumor tissues. Thus, ATO appears to have potential for the treatment of solid tumors, as well as hematopoietic malignancies.
To identify the genes related to atopic dermatitis (AD), we compared gene expression in eosinophils from AD patients and healthy volunteers. RNA was prepared from peripheral blood eosinophils. Gene expression was monitored by fluorescent differential display (DD) and real-time RT-PCR. Eighteen new sequences, including expressed sequence tags (ESTs), were expressed at higher levels in eosinophils from AD patients than in those from healthy volunteers. The functions of most of these genes are unknown. We found no correlation between the expression of a particular gene and clinical markers such as the number of eosinophils and the amount of IgE. Multivariate analysis of the gene expression data in each sample showed a very high coefficient of correlation among the copy numbers of each gene. The genes under investigation were also expressed in cultured blood eosinophils after IL-4, IL-5 and IFN-gamma stimulation. We were able to predict the function of some of the sequences by scanning for homologies within either the human or mouse genome databases. The mouse counterpart of one of these genes, intersectin 2, was expressed dramatically, as measured by ear edema, in 1-fluoro-2,4-dinitrobenzene-induced mouse contact dermatitis and in NC/Nga mouse dermatitis.
BACKGROUND: The physiological roles of eosinophils that accumulate in the uterus during pregnancy and of uterus-dwelling mast cells remain unknown. In the present study, we investigated the degranulation of eosinophils and mast cells within the normal course of pregnancy and after delivery by measuring the urinary concentrations of eosinophil-derived neurotoxin (EDN) and N-methylhistamine. METHODS: Spot urine samples from 65 pregnant women and 15 nonpregnant, age-matched women were examined. Urinary EDN and N-methylhistamine concentrations were measured by radioimmunoassay and standardized with urinary creatinine concentration. RESULTS: A significant increase in the urinary EDN concentration was observed until the second trimester in the normal pregnancies. The elevated urinary EDN levels decreased after the onset of labor in the third trimester and normalized within 1 month after normal vaginal delivery. In women who underwent a cesarean section, the urinary EDN concentration was significantly higher for up to 1 month after delivery, compared to that in women who underwent a vaginal delivery. In contrast, the urinary N-methylhistamine concentration did not change until the second trimester and was significantly decreased during the third trimester. No significant correlation between the peripheral blood eosinophil count and the urinary EDN concentration was observed in these subjects. CONCLUSIONS: Eosinophils appear to play a role in the progression of pregnancy and recovery after a cesarean section through the degranulation of eosinophils. In addition, mast cell degranulation does not appear to be related to the contraction of uterine smooth muscle during labor.
A cell growth inhibitory effect of drupanin and baccharin, ingredients of propolis, was found in human cancer cell lines. These compounds induced apoptosis in the cells characterized by morphological and nucleosomal DNA fragmentation analysis. Their effects were less potent compared with that of artepillin C, which is a known anticancer compound from propolis. Importantly, HL60 cells were more sensitive to drupanin than were Con A-stimulated peripheral blood lymphocytes, whereas the potency of artepillin C was the opposite of that of drupanin.
We examined the in vitro effects of the benzophenone derivatives garcinol, isogarcinol, and xanthochymol on cell growth in four human leukemia cell lines. All of the compounds exhibited significant growth suppression due to apoptosis mediated by the activation of caspase-3. A loss of mitochondrial membrane potential was found in garcinol- and isogarcinol-induced apoptosis, but not in xanthochymol-induced apoptosis. The growth inhibitory effects of isogarcinol and xanthochymol were more potent than that of garcinol, which is a well- known cytotoxic benzophenone derivative.
Aliphatic alpha,alpha-dibromo esters, precursors of ynolates, were synthesized via bromination of lithium alpha-bromo ester enolates with 1,2-dibromotetrafluoroethane in good yields. alpha-Trimethylsilyl-alpha,alpha-dibromo esters were synthesized via radical bromination.
Stilbene derivatives, which are resveratrol (3,4',5-trihydroxy-trans-stilbene) oligomers ranging from monomer to tetramer, isolated from Dipterocarpaceae plants were tested for their inhibitory effects against murine tyrosinase activity. The structure-activity relationships obtained in this study suggest that the double bond in the stilbene skeleton is critical for the inhibition, and also that molecular size is important for inhibitory potency.
Gnetol (2,3',5',6-tetrahydroxy-trans-stilbene), a naturally occurring compound particularly found in the genus Gnetum, had a strong inhibitory effect on murine tyrosinase activity. Gnetol (IC50, 4.5 microM) was stronger than kojic acid (IC50, 139 microM) as a standard inhibitor for murine tyrosinase activity. Moreover, gnetol significantly suppressed, melanin biosynthesis in murine B16 melanoma cells.
Explore the source record for details and available documents.
BACKGROUND: The anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) is known to reduce hepatic ischemia-reperfusion injury. Therefore, we wished to examine the effect of IL-1Ra gene delivery into the rat liver on hepatic ischemia-reperfusion injury. METHODS: IL-1Ra cDNA was delivered into the rat liver by a single injection of the transgene vector into the portal vein using either the plasmid-cationic liposome or the recombinant adenoviral vector. At 24 hours after the gene delivery, rats were subjected to partial liver ischemia for 90 minutes followed by reperfusion. Liver tissue and serum samples were taken at 180 minutes of reperfusion, and the degree of the liver injury as well as the expression level of pro-inflammatory cytokines in the serum and tissue were investigated. In addition, we assessed the effect of IL-1Ra gene delivery on the 7-day survival rate when the nonischemic liver lobe was partially excised immediately following reperfusion. RESULTS: In both cases of delivery methods, gene transfer of IL-1Ra resulted in significant elevation of serum IL-1Ra concentration, which reached maximal levels at 24 hours following the delivery. However, the highest serum concentration with the adenoviral vector was 1,000-fold of that in the liposome-treated animals. In the IL-1Ra delivered rats, liver damage, as well as production of pro-inflammatory cytokines, at 180 minutes of reperfusion was significantly reduced in a concentration-dependent manner of the circulating IL-1Ra protein. Rats subjected to the adenoviral vector gene delivery had higher 7-day survival rates compared with control animals. CONCLUSIONS: IL-1Ra gene delivery into the liver may be of therapeutic use for abrogating hepatic ischemia-reperfusion injury after transplantation.
Analysis of patients with atopic dermatitis (AD) for differential expression of genes, as compared to normal individuals, will be useful for understanding the molecular pathogenesis of AD. We found that the expression of the gene ETEA in human peripheral blood CD3-positive cells from patients with atopic dermatitis was significantly higher than in normal individuals. Eosinophils from AD patients expressed ETEA at a significantly higher level than the healthy controls. The overall sequence of the 445 aa deduced polypeptide from the cloned ETEA cDNA showed homology to human Fas-associated factor 1 (FAF1), which is involved in Fas-mediated apoptosis. However, the interaction of ETEA with the Fas death domain was weaker than that of FAF1, as studied in yeast two-hybrid experiments. The ETEA-EGFP fusion protein was expressed in cytoplasm. During the course of activation-induced cell death of primary T cells, transcription levels of ETEA and FAF1 were upregulated with similar kinetics. The enhanced expression of ETEA may play a role in the regulating the resistance to apoptosis that is observed in T cells and eosinophils of AD patients.
BACKGROUND: The mechanism of hyporesponsiveness induced by intratracheal (IT) delivery of alloantigen was examined and its effect on cardiac graft survival was assessed in studies in mice. METHODS: In CBA (H2 ) mice, donor splenocytes were given by IT delivery 7 days before transplantation of a C57BL/10 (H2 ) heart. To determine whether regulatory cells were involved in hyporesponsiveness, splenocytes from mice given IT delivery of alloantigen and antibodies for B7-1, B7-2, or CTLA4 were adoptively transferred to naïve secondary recipients 7 days after delivery; those recipients underwent heart transplantation the same day. Effects on cell proliferation and cytokine production of splenocytes from mice given IT delivery of alloantigen were examined in mixed leukocyte cultures (MLC). RESULTS: Cardiac graft survival was significantly prolonged in mice given IT delivery of alloantigen (median survival time [MST], 81 days); those given syngeneic splenocytes rejected grafts acutely (MST, 7 days; P<0.05). Adoptive transfer of splenocytes also significantly prolonged survival of cardiac grafts in secondary recipients (MST, 62 days). When B7-1, B7-2, or CTLA4 antibody was combined with IT delivery of alloantigen in the first recipient, all grafts were rejected within 14 days in second recipients after adoptive transfer. In mixed leukocyte cultures, splenocytes from these mice did not respond to alloantigen and production of interleukin-4 and interleukin-10 was increased. CONCLUSIONS: Donor splenocytes delivered IT induced hyporesponsiveness and regulatory cells in our animal model, and such induction was dependent on B7-1, B7-2, and CTLA4 signals.
Rodent mast cells (MCs) are common experimental tools but are somewhat different from their human counterparts in their responses to certain cytokines and drugs. We examined the expression of more than 10 000 distinct genes in human and mouse cultured MCs using high-density oligonucleotide probe arrays to find molecules similarly regulated and expressed by the 2 MC types. After stimulation via high-affinity Fcepsilon receptor I (FcepsilonRI), the transcriptional levels of several CC chemokines were markedly increased, and I-309 (CCL1), macrophage inflammatory protein-1alpha (MIP-1alpha) (CCL3) and MIP-1beta (CCL4) were found among the 10 most increased human and mouse transcripts from approximately 12 000 genes (including some expressed sequence tags). In addition, a costimulatory molecule that was originally found on the membrane of activated T cells, 4-1BB (CD137), was found among the 10 most increased transcripts. The FcepsilonRI-induced expression of CC chemokines and 4-1BB was also detected at the protein level in both MC types. The conservation of these responses suggests that MCs play a crucial role in recruitment of various CCR-expressing cells into the tissue in a manner dependent on immunoglobin E, and that FcepsilonRI-mediated induction of several CC chemokines and 4-1BB is highly conserved between human and mouse. Interspecies comparison studies at the whole genome expression level should be useful for the interpretation of experimental data obtained in animal models of human pathobiology.
We have developed the first general method for a stereoselective olefination of acylsilanes via ynolate anions to produce (Z)-beta-silyl-alpha,beta-unsaturated ester, which leads to tri- and tetrasubstituted alkenes.
One-stage surgical management of concomitant abdominal aortic aneurysm (AAA) and gastric or colorectal cancer should provide certain benefits. We reviewed the records of 21 patients with both AAA and gastric or colorectal cancer who underwent one-stage surgical management. Four had distal gastrectomy, 2 had total gastrectomy, and 5 had abdominoperineal rectal resection transperitoneally; 3 had total gastrectomy transperitoneally and AAA repair extraperitoneally. Two underwent right hemicolectomy and thromboexclusion of the AAA. Two had creation of a temporary ileostomy and implantation of an interposition graft. Two underwent left hemicolectomy, creation of a temporary transversostomy, and implantation of an interposition graft. One had a Hartmann's procedure and implantation of a bifurcated prosthetic interposition graft for AAA. There were no operative deaths or serious postoperative complications. One patient had colorectal ischemia that resolved with conservative treatment. Eighteen of the 21 patients (85.7%) were alive 10 months to 14 years postoperatively. In conclusion, one-stage surgical treatment of concomitant AAA and gastric or colorectal cancer is well tolerated and can avoid the time, financial costs, and patient anxiety involved in a second operation.
Tenascin-C (TNC) knockout (TNKO) mice showed reduced proliferation of mesangial cells and abnormal restoration after habu-snake venom (HSV)-induced glomerulonephritis. In this study, we examined the relationship of TNC and platelet-derived growth factor receptor (PDGFR) in glomerular mesangial cells. TNC and PDGFR-alpha and -beta transcriptions were up-regulated in wild type (WT) mice after HSV injection, but in TNKO mice PDGFR-alpha transcription was not up-regulated. Immunohistochemistry showed that PDGFR-alpha was found in mesangial areas of colocalized alpha-smooth muscle actin, but in TNKO mice it was not detectable. In vitro studies showed that the expressions of PDGFR-alpha and -beta mRNA and protein in cultured glomerular mesangial cells (GMC) of TNKO mice were lower than those in WT GMC. These results suggest that failures of both TNC and PDGFR-alpha are a candidate for abnormal restoration of TNKO mice.
Extracellular matrix glycoprotein tenascin-C (TNC) expression is up-regulated in tissue remodeling processes such as tumorigenesis and wound healing. Mouse tenascin-C contains six alternatively spliced domains (A1, A2, A4, B, C, and D) between the fifth and the sixth type III fibronectin domains, which generate large numbers of TNC isoforms. To study TNC isoform variability of wound healing in mice, we induced glomerulonephritis by using Habu snake venom (HSV) and examined alternatively spliced regions by the reverse transcription polymerase chain reaction (RT-PCR) technique. RT-PCR products were separated into seven bands in both healthy and diseased kidneys. Among the seven bands, those containing one or five alternatively spliced domains were mainly up-regulated from 2 days to 1 week after HSV injection. Southern blotting revealed that only domain-D detected all six bands in both healthy and diseased kidneys. Furthermore, only the domain-C transcriptional level did not show an obvious change in progress following HSV injection. These results suggested that (a) the isoforms containing one or five alternatively spliced domains play important roles in the healing process of glomerulonephritis, (b) domain-D is particularly significant in kidney, and (c) domain-C may not play an important role in the healing process of HSV-induced glomerulonephritis.