Influence of physical activity on warfarin therapy.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to H Hashimoto.
Explore the source record for details and available documents.
The relation between vascular endothelial growth factor (VEGF) and advanced glycation end product (AGE) is considered a primary factor in the development of diabetic retinopathy. Regarding the relation between VEGF in the vitreous body and pentosidine, an AGE, we compared a diabetic (DM) group (7 eyes) with a nondiabetic (nonDM) group (7 eyes), and investigated the correlation between VEGF and pentosidine by calculating the correlation coefficient. Levels of both VEGF and pentosidine were significantly higher in the DM group (p < 0.01, p < 0.05), and a positive correlation was observed between the levels of VEGF and pentosidine (r = 0.770, p < 0.001). Since it is clear that there is a relation between VEGF and pentosidine in the vitreous body, we speculated that AGE is related to the secretion of cytokine in patients with diabetic retinopathy, and that it affects the development and progression of the disease.
A 35-year-old man with non-Hodgkin's lymphoma (NHL) (follicular small cleaved, B cell, stage IVB) received double myeloablative chemotherapy with syngeneic peripheral blood stem cell transplantation (PBSCT). Although platelet recovery was delayed until day 29 after the second transplantation, thereafter trilineage hematopoietic reconstitution was achieved. The evaluation after PBSCT did not detect any residual tumor. The patient was in good health until day 138, when his platelet count suddenly began falling; on day 150, it had fallen to 1.5 x 10(4)/microliter, and the patient was re-admitted for treatment. The bone marrow was normocellular with a normal count and megakaryocyte structure. Other examinations, including serological tests and computed tomography of the neck, chest, abdomen, and retroperitoneum, did not indicate a recurrence of NHL or reveal the cause of thrombocytopenia. The patient's platelet-associated IgG (PAIgG) level was at 70.9 ng/10(7) platelets (normal range: 9-25 ng/10(7) platelets); a diagnosis of thrombocytopenia due to an autoimmune mechanism such as idiopathic thrombocytopenic purpura (ITP) was made. Prednisolone therapy increased the platelet count and reduced the PAIgG level. Thrombocytopenia with an ITP-like mechanism rarely occurs more than 100 days after autologous or syngeneic stem cell transplantation, and should be taken into consideration as a late complication of PBSCT.
We report the 13th case of accessory spleen in the retroperitoneum in the world literature. A 53-year-old man visited our hospital complaining of lassitude. Laboratory studies revealed significant anemia. Several imaging studies revealed a large retroperitoneal tumor (70 x 63 x 48 mm) in the medial aspect of the lower pole of the left kidney. The tumor was supplied arterially from the first and second lumbar arteries. Since the tumor adhered tightly to the left kidney, the kidney was resected as well as the tumor. The tumor was very hemorrhagic. On histological examination, the tumor exhibited a structure typical of splenic tissue. The retroperitoneal accessory spleen is very rare, and the literature on it is reviewed here.
Three type II membrane proteins Anp1, Van1 and Mnn9 of Saccharomyces cerevisiae share significant sequence homology. Their precise biochemical activity has long been unknown though the mutant phenotype indicates their participation in protein glycosylation in the Golgi apparatus. To shed light on their molecular characteristics, interactions of these proteins were studied by immunoprecipitation after solubilizing the membrane by nonionic detergent. Our results indicated that there are at least two submembrane complexes containing these proteins: one contains Van1 and Mnn9 proteins and the other contains Anp1 and Mnn9 proteins. In addition, Hoc1 protein which has significant homology to Och1 protein colocalized with Anp1 and Mnn9 proteins. These complexes with similar but partially different constituents may represent essential parts of glycosylation machinery in the yeast Golgi compartments.
It has been believed that the Fas expressed on human peripheral blood T cells (PBT) is nonfunctional, because these cells are insensitive to agonistic anti-Fas/Apo-1 mAbs that efficiently kill in vitro-activated T cells and many Fas-expressing cell lines. Here, we demonstrate that membrane-bound Fas ligand (FasL) kills both fresh and in vitro-activated PBT, indicating that the Fas expressed on fresh PBT is functional. In contrast, soluble FasL kills only the latter. Naive T cells in umbilical cord blood do not express Fas, but can be induced to express Fas by IFN-gamma or by a combination of IL-2 and anti-CD28 mAb, after which they acquire sensitivity to membrane but not to soluble FasL. Soluble FasL inhibited the killing of fresh PBT by membrane FasL. These results indicate that the shedding of FasL from the membrane is a mechanism for downregulating at least part of its killing activity.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A genomic DNA fragment that complements a newly identified protein glycosylation-defective mutation, vig9, of Saccharomyces cerevisiae was cloned. Chromosomal integration of this fragment by homologous recombination indicated that it contains the wild type VIG9 gene. The nucleotide sequence was determined. A predicted gene product showed significant amino acid sequence homology with several bacterial enzymes that catalyze the synthesis of (deoxy)ribonucleotide diphosphate sugars from sugar phosphates and (deoxy)ribonucleotide triphosphate. We examined the enzyme activity to synthesize GDP-mannose in the cell extracts of the wild type, vig9-1 mutant, and VIG9 transformant yeasts. Reduction of the activity in the mutant cell and its restoration by VIG9 suggested that the VIG9 gene is the structural gene for GDP-mannose pyrophosphorylase of S. cerevisiae which catalyzes the production of GDP-mannose. We demonstrated the enzyme activity of Vig9 protein using a recombinant fusion protein produced in Escherichia coli.
The incorporation of zwitterionic residues (5-substituted omega-aminoalkyl-2'-deoxypyrimidines) into DNA has been reported to bend DNA as measured by aberrant gel mobility [Strauss et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 9515-9520]. Herein we report that DNA methylation by N-methyl-N-nitrosourea at N7-guanine is regioselectively inhibited by point substitutions of the zwitterionic residues 5-(6-aminohexyl)-2'-deoxycytidine, 5-(6-aminohexyl)-2'-deoxyuridine, or 5-(3-aminopropyl)-2'-deoxyuridine. No inhibition is observed for DNA methylation by dimethyl sulfate. On the basis of inhibition patterns for methylation with the different zwitterionic substitutions and the different length tethers, the omega-aminoalkyl side chains prefer to adopt a conformation that points them toward the 3'-base. Molecular modeling grid searches, coupled with energy minimizations, and simulated annealing molecular dynamics studies indicate that unfavorable steric interactions with the 5'-base and backbone, as well as stabilizing electrostatic interactions with electronegative atoms on the 3'-side, are responsible for the observed conformational preference. No evidence for association of the cationic side chain with the phosphate backbone is observed. The observed bending of DNA induced by the tethered ammonium ions may simply arise from their localization in the major groove.
The distribution of mRNAs for pituitary adenylate cyclase-activating polypeptide (PACAP), PACAP receptor (PACAP-R), vasoactive intestinal polypeptide (VIP) and two subtypes of VIP receptors (VIP1-R and VIP2-R) was examined by in situ hybridization in the superior cervical ganglion (SCG) of the adult rat. PACAP-R mRNA was expressed intensely in virtually all principal neurons. PACAP mRNA was expressed in approximately half of the principal neurons, where the levels of expression vary extensively. Intense expression of VIP mRNA was observed only in a few principal neurons. Neither VIP1-R mRNA nor VIP2-R mRNA was detected in SCG cells. These findings suggest that PACAP, but not VIP, may function as a paracrine or autocrine regulatory factor through PACAP-R in the principal neurons of the SCG.
Explore the source record for details and available documents.
BACKGROUND: Myxoid liposarcoma is one of the major myxoid malignancies of soft tissue and its histologic differentiation from other myxoid tumors is sometimes difficult. Recent cytogenetic analysis revealed that a characteristic reciprocal chromosomal translocation of t(12;16)(q13;p11) occurs in myxoid liposarcomas. In this study, retrospective cytogenetic analysis by means of fluorescence in situ hybridization (FISH) and DNA flow cytometry were performed on free nuclei isolated from paraffin embedded myxoid liposarcoma cells, and they were compared with myxoid malignant fibrous histiocytomas (MFHs), low grade fibromyxoid sarcomas, and intramuscular myxomas. METHODS: Nine myxoid liposarcomas, five myxoid MFHs, two low grade fibromyxoid sarcomas, and four intramuscular myxomas were examined. Chromosomal aberrations in chromosomes 12 and 16 were investigated by FISH, using both centromeric DNA probes and whole chromosome painting probes. Cellular DNA contents were determined by flow cytometry. RESULTS: All nine myxoid liposarcomas were shown to be diploid by DNA flow cytometry and exhibited the translocation t(12; 16), as shown by FISH. Four of the five myxoid MFHs exhibited aneuploidy, as shown by flow cytometry, and remarkable numeric aberrations of chromosomes 12 and 16. No abnormal DNA content or chromosomal aberrations were identified in the two low grade fibromyxoid sarcomas or the four intramuscular myxomas. CONCLUSIONS: FISH analysis performed on paraffin embedded materials can be used to differentiate myxoid liposarcomas from other myxoid soft tissue tumors.
A spontaneous dwarf rat derived from a colony of Sprague-Dawley (SD) strain has no detectable level of growth hormone (GH) in pituitary, although it contained other hormones like prolactin and ACTH. Hepatic profile of cytochrome P450 (P450) differed clearly between dwarf and normal SD rats. A male-specific form of P450, CYP2C11, was detected in dwarf male rat livers, while the level was one-third of the normal SD livers. This P450 was also detected in dwarf females. Other male-specific CYP3A2 and CYP3A18 were also contained in both sexes of dwarf rats, whereas a female-specific form, CYP2C12, was not detectable in dwarf females. Phenobarbital-inducible CYP2B1 and CYP2B2 were constitutively expressed in dwarf rats, although substantially absent in normal SD rats. To assess the role of GH on hepatic P450 expression, GH was given to dwarf rats for 7 to 9 days. The intermittent injection (mimicking the male secretory pattern) resulted in the elevation of CYP2C11 to a level as observed in normal SD males. Continuous infusion of GH (mimicking the female secretory pattern) evoked CYP2C12 in livers of both sexes of dwarf rats, whereas the treatment decreased levels of CYP3A2, CYP3A18, and CYP2B1. These results clearly demonstrate that specific defect of GH, but not pituitary, cause the clear changes in hepatic P450 forms including sex-specific forms. The present study provides evidence further to strengthen the principal role of GH on the regulation of expression of P450 in rat livers.
OBJECTIVE: To establish a system for efficient, direct in vivo gene transfer into joints. METHODS: A hemagglutinating virus of Japan (HVJ; Sendai virus)-liposome suspension containing SV40 large T antigen (SVT) gene was injected intraarticularly into knee joints of 6-week-old female Lewis rats. Rats were killed at various times for immunohistochemical analysis of the expression of SVT gene. RESULTS: The expression of SVT gene was detected immunohistochemically in chondrocytes in the superficial and middle zones of articular cartilage in the knee joints. The average percentage of SVT-positive cells was estimated to be approximately 30% on days 3, 7, 14, and 21 after transfection. Moreover, no pathologic change caused by HVJ-liposome injection was observed in the joints. CONCLUSION: The transfection frequency and stability of expression recognized in this study indicate the possibility of a strategy for treatment of joint disorders, including arthritis, using direct gene transfer.
An adequate supply of peripheral blood monocytes, granulocytes, and platelets is necessary for an optimal inflammatory process. We have previously demonstrated that the generation of CD14(+) monocyte-lineage cells from the bone marrow is accelerated in patients with rheumatoid arthritis (RA). The current studies examined the influences of gold sodium thiomalate (GST) and bucillamine (BUC), two potent disease-modifying antirheumatic drugs (DMARDs), on the capacity of bone marrow progenitor cells to generate CD14(+) cells in patients with RA, in order to delineate their mechanisms of action. CD14(-) cells purified from bone marrow specimens of 13 patients with active RA who were not taking DMARDs were cultured in the presence or absence of pharmacologically attainable concentrations of GST (25 microM) or intramolecular disulfide form of bucillamine (BUC-ID, 3 microM), a major metabolite of BUC. After incubation for 14 days, the cells were analyzed by flow cytometry for expression of CD14, HLA-DR, and CD54. The generation of CD14(+) cells from RA bone marrow CD14(-) progenitor cells was significantly suppressed by GST, but not by BUC-ID. The expression of HLA-DR on the bone marrow-derived CD14(+) cells was also significantly inhibited by GST, but not by BUC-ID. Of note, neither GST nor BUC-ID influenced the expression of CD54 on the bone marrow-derived CD14(+) cells, indicating that the expression of HLA-DR and CD54 on the bone marrow-derived CD14(+) cells is regulated by different mechanisms. The results are consistent with the hypothesis that one of the effects of DMARDs may involve the interference with monocyte differentiation in the bone marrow. Moreover, the data emphasize that in contrast with BUC, GST is a potent inhibitor of monopoiesis in RA patients.
Patients whose colons were resected for carcinoma were studied in order to determine the relationship between clinical findings-which included development of postoperative delirium- and intramitochondrial inclusion bodies (MI) in the neurons in the colon. Twenty-three patients had MI and 24 patients did not. Preoperative dementia was present in 9 (39.1%) of the 23 patients with MI, and in 7 (29.2%) of the 24 without it. Postoperative delirium developed in 13 (56.3%) of the 23 with MI, and in 5 (20.8%) of the 24 without it (p < 0.05). Excluding preoperative dementia, postoperative delirium developed in 5 (35.7%) of the 14 with MI, and in none of the 17 without it. Changes in the neurons in the colon were not related to dementia. The changes may have been related to the functions of the central nervous system, because patients with MI were likely to develop postoperative delirium.
The case of a 49-year-old man with Maffucci's syndrome, who developed multiple spindle cell hemangioendotheliomas, is presented. The case provides support for recent reports suggesting an association between this peculiar vascular lesion and skeletal enchondromatosis.