[Serum immunological diagnosis of Anisakis infection].
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Animals↗
Biomedical subjects
Y Yamaguchi
Publications and source records attributed to Y Yamaguchi.
Peritubular capillary deposition of C4d complement fragment in ABO-incompatible renal transplantation with humoral rejection.
In ABO-incompatible renal transplantation complement activation may be related to antibody-associated humoral rejection. However, immune deposits within the vasculature have been infrequently demonstrated in biopsy specimens. Whether deposition of complement fragment C4d is correlated with graft outcome and pathological findings (as measured by the severity of antibody-associated humoral rejection) is investigated in this study. Nineteen ABO-incompatible and 9 ABO-compatible renal graft biopsy specimens were selected. Four out of 19 ABO-incompatible patients lost their grafts within 1 yr. Ten out of 19 ABO-incompatible and just 1 out of 9 ABO-compatible patients, had prominent C4d deposition in peritubular capillaries. ABO-incompatible patients with predominant C4d deposition showed few tubulitis, accumulation of polymorphonuclear cells and thrombosis in peritubular and glomerular capillaries. The severity of the humoral rejection was correlated to C4d deposition in peritubular capillaries. Three out of four graft losses in ABO-incompatible renal transplantation showed severe humoral rejection and profuse deposition of C4d complement fragments in peritubular capillaries. Immunosuppression therapy was discontinued in the 4th patient, who lost his graft because of his lethal intestinal bleeding. C4d deposition in peritubular capillaries would be helpful for differential diagnosis between humoral rejection and drug-induced nephrotoxicity, and may serve as a sensitive marker of ABO-incompatible humoral rejection for patients with unsatisfactory (no glomeruli) biopsy specimens.
ABO Blood-Group System↗
Clinical and histological analysis of acute tacrolimus (TAC) nephrotoxicity in renal allografts.
UNLABELLED: Tacrolimus (TAC) is an effective primary immunosuppressive agent in kidney transplantation. Acute nephrotoxicity due to TAC in kidney transplant patients is either similar to, or significantly more frequent than that of cyclosporin A (CsA). In this study we describe the clinico-morphologic characteristics of acute TAC nephrotoxicity in kidney transplant recipients. PATIENTS AND METHODS: We studied retrospectively the clinical courses of 67 patients who underwent kidney transplantation under TAC immunosuppression at Tokyo Women's Medical University between July 1990 and January 1997. We compared the recipient's characteristics with and without acute TAC nephrotoxicity. We also studied retrospectively the clinico-morphologic profiles of the acute TAC nephrotoxicity with 16 kidney transplant recipients under TAC immunosuppression, who were diagnosed with acute TAC nephrotoxicity by allograft biopsies between January 1996 and January 1997. RESULTS: There were no significant differences between acute TAC nephrotoxicity and non-nephrotoxicity groups about age, sex, donor source, age of donor, the proportion of ABO incompatible and the number of human leukocyte antigen (HLA) mismatches. Of 27 acute TAC nephrotoxicity recipients, 7 patients (26%) had moderate-to-severe grade arteriosclerosis in their allograft arteries. The onset of TAC nephrotoxicity occurred 8-69 days post-operatively. The baseline creatinine level was 1.92 mg/dL (range 0.4-5.1 mg/dL) and rose by 38.4% (range 0-84.6) during episodes of nephrotoxicity. The mean peak of the whole blood TAC trough level during the toxic episodes was 32.5 ng/mL (range 21.2-58.5 ng/mL). The rise in creatinine level preceded the highest TAC level in 10 cases. A mean reduction in TAC dosage of 18.9% (range 0-50% led to a fall of 17.2% (range 0-43%) in serum creatinine levels. The moderate-to-severe arteriosclerosis in allograft arteries was seen in 5 (31%) patients. CONCLUSION: The high trough level of the whole blood TAC and the existence of moderate-to-severe arteriosclerosis in allograft arteries have the potential of causing TAC nephrotoxicities. A reduction of TAC dosage may be effective in improving allograft functions.
Adult↗
Expression and functional analysis of a hemopoietic progenitor antigen, NJ-1 (114/A10), in the megakaryocytic lineage.
To analyze the functions of molecules expressed in hemopoietic progenitor cells, we obtained several monoclonal antibodies by immunizing Wistar rats with antigens from a murine immature leukemic cell line, DA-1. Here, we characterize one antibody designated NJ-1, which recognizes a 145-kd molecule, and identify the cDNA encoding the NJ-1 antigen by retrovirus-mediated expression cloning. Sequence analysis of the cDNA reveals that it is identical to a previously reported cDNA encoding a surface molecule of 573 amino acids recognized by monoclonal antibody 114/A10. Our studies show that expression of NJ-1 antigen is upregulated in a murine megakaryoblastic cell line, L8057, when it differentiates into a megakaryocytic lineage in response to 12-O-tetradecanoyl phorbol-13-acetate. Overexpression of NJ-1 antigen in L8057 cells inhibits cell adhesion to fibronectin, suggesting that it may act as a negative regulator of cell adhesion in the megakaryocytic lineage.
Animals↗
Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro.
Recently, a positive and a negative elongation factor, implicated in 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) inhibition of transcription elongation, has been identified. P-TEFb is a positive transcription elongation factor and the DRB-sensitive kinase that phosphorylates the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II). PITALRE, a member of the Cdc2 family of protein kinases, is the catalytic subunit of P-TEFb. DSIF is a human homolog of the yeast Spt4-Spt5 complex and renders elongation of transcription sensitive to DRB. DRB sensitivity-inducing factor (DSIF) binds to RNA Pol II and may directly regulate elongation. Here we show a functional interaction between P-TEFb and DSIF. The reduction of P-TEFb activity induced by either DRB, antibody against PITALRE, or immunodepletion resulted in a negative effect of DSIF on transcription. DSIF acts at an early phase of elongation, and the prior action of P-TEFb makes transcription resistant to DSIF. The state of phosphorylation of CTD determines the DSIF-RNA Pol II interaction, and may provide a direct link between P-TEFb and DSIF. Taken together, this study reveals a molecular basis for DRB action and suggests that P-TEFb stimulates elongation by alleviating the negative action of DSIF.
Cyclin-Dependent Kinase 9↗
Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor.
The new neuropeptide Y (NPY) Y5 receptor antagonist CGP 71683A displayed high affinity for the cloned rat NPY Y5 subtype, but > 1, 000-fold lower affinity for the cloned rat NPY Y1, Y2, and Y4 subtypes. In LMTK cells transfected with the human NPY Y5 receptor, CGP 71683A was without intrinsic activity and antagonized NPY-induced Ca2+ transients. CGP 71683A was given intraperitoneally (dose range 1-100 mg/kg) to a series of animal models of high hypothalamic NPY levels. In lean satiated rats CGP 71683A significantly antagonized the increase in food intake induced by intracerebroventricular injection of NPY. In 24-h fasted and streptozotocin diabetic rats CGP 71683A dose-dependently inhibited food intake. During the dark phase, CGP 71683A dose-dependently inhibited food intake in free-feeding lean rats without affecting the normal pattern of food intake or inducing taste aversion. In free-feeding lean rats, intraperitoneal administration of CGP 71683A for 28 d inhibited food intake dose-dependently with a maximum reduction observed on days 3 and 4. Despite the return of food intake to control levels, body weight and the peripheral fat mass remained significantly reduced. The data demonstrate that the NPY Y5 receptor subtype plays a role in NPY-induced food intake, but also suggest that, with chronic blockade, counterregulatory mechanisms are induced to restore appetite.
Animals↗
Mouse K-glypican gene, gpc4, maps to chromosome X.
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Animals↗
Human monocytoid leukemia cells are highly sensitive to apoptosis induced by 2'-deoxycoformycin and 2'-deoxyadenosine: association with dATP-dependent activation of caspase-3.
The adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (dCF) significantly inhibits the proliferation of leukemia and lymphoma cell lines. When cells were incubated in the presence of both dCF and 2'-deoxyadenosine (dAd), the concentration of dCF required to induce apoptosis of monocytoid leukemia cells was much lower than that required for myeloid, erythroid, or lymphoma cell lines. Among the cell lines tested, U937 cells were the most sensitive to this treatment. The concentration of dCF that effectively inhibited the proliferation of U937 cells was 1/1,000 of that required for lymphoma cell lines, on a molar basis. However, the uptake of dCF or dAd in U937 cells was comparable with that in other leukemia and lymphoma cell lines. The intracellular accumulation of dATP in U937 cells was only slightly higher than that in other leukemia cells in dCF-treated culture. Treatment with dCF plus dAd induced apoptosis in U937 cells at low concentrations, and this apoptosis was reduced by treatment with caspase inhibitors. Induction of caspase-3 (CPP32) activity accompanied the apoptosis induced by dCF plus dAd. No activation of CPP32 was observed in cytosol prepared from exponentially growing leukemia and lymphoma cells. However, dATP effectively induced CPP32 activation in cytosol from monocytoid cells, but not in that from nonmonocytoid cells, suggesting that dATP-dependent CPP32 activation is at least partly involved in the preferential induction of apoptosis in monocytoid leukemia cells. The combination of dCF and dAd may be useful for the clinical treatment of acute monocytic leukemia.
Apoptosis↗
Site-directed mutational analysis for the membrane binding of DnaA protein. Identification of amino acids involved in the functional interaction between DnaA protein and acidic phospholipids.
DnaA protein, the initiator of chromosomal DNA replication in Escherichia coli, interacts with acidic phospholipids, such as cardiolipin, and its activity seems to be regulated by membrane binding in cells. In this study we introduced site-directed mutations at the positions of hydrophobic or basic amino acids which are conserved among various bacteria species and which are located in the putative membrane-binding region of DnaA protein (from Asp357 to Val374). All mutant DnaA proteins showed much the same ATP and ADP binding activity as that of the wild-type protein. The release of ATP bound to the mutant DnaA protein, in which three hydrophobic amino acids were mutated to hydrophilic ones, was stimulated by cardiolipin, as in the case of the wild-type protein. On the other hand, the release of ATP bound to another mutant DnaA protein, in which three basic amino acids were mutated to acidic ones, was not stimulated by cardiolipin. These results suggest not only that the region is a membrane-binding domain of DnaA protein but also that these basic amino acids are important for the binding and the ionic interaction between the basic amino acids and acidic residues of cardiolipin and is involved in the interaction between DnaA protein and cardiolipin.
Adenosine Diphosphate↗
Constitutively active Galpha12, Galpha13, and Galphaq induce Rho-dependent neurite retraction through different signaling pathways.
In neuronal cells, activation of a certain heterotrimeric G protein-coupled receptor causes neurite retraction and cell rounding via the small GTPase Rho. However, the specific heterotrimeric G proteins that mediate Rho-dependent neurite retraction and cell rounding have not yet been identified. Here we investigated the effects of expression of constitutively active Galpha subunits on the morphology of differentiated PC12 cells. Expression of GTPase-deficient Galpha12, Galpha13, and Galphaq, but not Galphai2, caused neurite retraction and cell rounding in differentiated PC12 cells. These morphological changes induced by Galpha12, Galpha13, and Galphaq were completely inhibited by C3 exoenzyme, which specifically ADP-ribosylates and inactivates Rho. The tyrosine kinase inhibitor tyrphostin A25 blocked the neurite retraction and cell rounding induced by Galpha13 and Galphaq. However, tyrphostin A25 failed to inhibit the Galpha12-induced neuronal morphological changes. On the other hand, inhibition of protein kinase C or elimination of extracellular Ca2+ blocked the neurite retraction and cell rounding induced by Galphaq, whereas the morphological effects of Galpha12 and Galpha13 did not require activation of protein kinase C and extracellular Ca2+. These results demonstrate that activation of Galpha12, Galpha13, and Galphaq induces Rho-dependent morphological changes in PC12 cells through different signaling pathways.
ADP Ribose Transferases↗
Tumor necrosis factor-beta is associated with thymic apoptosis during acute rejection.
BACKGROUND: Intrathymic events undergoing allograft rejection remain undefined. The present study investigated the role of tumor necrosis factor-beta on acute thymic involution in rat hepatic allograft recipients during rejection. METHODS: Apoptosis and cellular phenotypic changes in the thymus were studied after hepatic transplantation. RESULTS: Thymocytes in both the medulla and cortex were sparse during acute rejection. Phenotypically, CD4+CD8+ T cells decreased significantly, whereas there were relative increases in CD4-CD8-, CD4+CD8-, and CD4-CD8+ T cells in untreated allograft recipients. Additionally, thymic apoptosis was found by in situ DNA end labeling and electron microscopy. Apoptotic cells were predominantly distributed in the cortex. Biologic lymphotoxin (tumor necrosis factor-beta)/tumor necrosis factor-alpha cytotoxic activity in the serum was significantly increased in untreated hepatic allograft recipients. Tumor necrosis factor-beta mRNA was detected in untreated allograft livers, and intraperitoneal administration of recombinant human tumor necrosis factor-beta induced extensive apoptosis of thymocytes in vivo. In contrast, no significant thymic involution was observed in donor-specific blood transfusion-treated allograft and isograft recipients. Intraperitoneal administration of rabbit anti-human tumor necrosis factor-beta polyclonal antibody or recombinant human interleukin-10 inhibited thymic apoptosis in untreated hepatic allograft recipients. CONCLUSIONS: Allograft rejection, but not donor-specific transfusion-induced immunologic unresponsiveness, is associated with thymic involution, a process that may be mediated by tumor necrosis factor-beta.
Acute Disease↗
GATA-3 represses gp91phox gene expression in eosinophil-committed HL-60-C15 cells.
To study the regulatory mechanism of gp91phox gene expression in eosinophils, we transiently transfected eosinophil-committed HL-60-C15 cells with gp91phox promoter constructs, and identified a negative element from bp -267 to -246 of the gp91phox gene, the deletion of which caused an 83% increase in promoter activity. Electrophoresis mobility shift assays demonstrated GATA-3 binds to the GATA consensus site from bp -256 to -250. An 81% increment in promoter activity was obtained when a mutation was introduced in the GATA-3 binding site of the bp -267 to +12 construct, which is comparable to that of the bp -245 to +12 construct. We therefore conclude that GATA-3 specifically binding to the GATA site negatively regulates the expression of the gene in HL-60-C15 cells.
Base Sequence↗
GPC4, the gene for human K-glypican, flanks GPC3 on xq26: deletion of the GPC3-GPC4 gene cluster in one family with Simpson-Golabi-Behmel syndrome.
The glypicans constitute a growing family of cell surface heparan sulfate proteoglycans that may play a role in the control of cell division and growth regulation. Recently, deletions and translocations involving GPC3 (the gene for glypican-3, localized on Xq26) have been identified in patients with Simpson-Golabi-Behmel syndrome (SGBS). This X-linked syndrome is characterized by pre- and postnatal overgrowth, visceral and skeletal abnormalities, and a high risk for the development of embryonal tumors, mostly Wilms tumor and neuroblastoma. In the present report we show that the gene for human K-glypican/glypican-4 (GPC4) also maps to Xq26, centromeric to GPC3. The glypican-4 protein is encoded by nine exons. Establishment of a BAC/PAC contig physically linking GPC4 and GPC3 indicates that these two genes are arranged in a tandem array, the 5' end of GPC4 flanking the 3' end of GPC3. Unlike the glypican-3 message, the glypican-4 message is nearly ubiquitous. Analysis of DNA samples from eight patients with diagnosis of SGBS identified one individual with a deletion that involves the entire GPC4 gene and the last two exons of GPC3. The tight clustering of GPC3 and GPC4, with deletions that occasionally affect both genes, may be relevant for explaining the variability of the SGBS phenotype.
Amino Acid Sequence↗
Differences in the evolutionary pattern of feline panleukopenia virus and canine parvovirus.
Canine parvovirus (CPV) suddenly appeared in the late 1970s after which it showed continuous antigenic changes. Virological and molecular genetic analyses mainly focused on feline panleukopenia virus (FPLV) were conducted in this study because FPLV is the suspected ancestor of CPV; the way in which FPLV evolves may help to explain the emergence of CPV. Analysis of escape mutants against FPLV-specific monoclonal antibody showed that viruses possessing CPV-like properties were not easily detected in FPLV virus stocks. Phylogenetic analysis revealed that the nonstructural protein 1 (NS1) and capsid protein 2 (VP2) genes of FPLV changed with time. A similar tendency, however, was not observed in the FPLV VP2 proteins. In contrast, the topology of the phylogenetic tree of VP2 proteins of CPV basically concurred with that of the VP2 genes. Analysis of the ratio of nonsynonymous and synonymous substitutions revealed that synonymous substitutions exceeded nonsynonymous substitutions in both the NS1 and VP2 genes of FPLV, even when the analysis focused on specific regions in the VP2 gene that are known to be located on the capsid surface. Comparison of the CPV VP2 genes revealed that nonsynonymous substitution was found to dominate over synonymous substitution in one specific region in the VP2 gene. These results suggested that FPLV has changed mainly by random genetic drift. In contrast, after the appearance of CPV, changes in the CPV VP2 gene appear to be partly selected by certain positive selection forces. CPV and FPLV are known to be closely related viruses genetically and biologically, but the evolutionary mechanisms of the two viruses appeared to be different.
Amino Acid Substitution↗
Anion-exchange high-performance liquid chromatographic assay of plasma lipoproteins of rabbits, rats and mice.
A fast, accurate and precise high-performance liquid chromatographic assay method has been developed for plasma lipoproteins of experimental animals, rabbits, rats and mice. The method includes complete separation of high, low and very low density lipoproteins from one another within 20 min by a DEAE-glucomannan gel using stepwise elution, and determination by postcolumn reaction with an enzymatic cholesterol reagent as the total cholesterol level. The relative standard deviation of each lipoprotein assay was highly reproducible, being less than 2.0 and 2.4% for repeatability and intermediate precision, respectively. The method was successfully applied to the assays of plasma lipoproteins in three species of normolipidemic and hyperlipidemic animals.
Animals↗
EBI1/CCR7 is a new member of dendritic cell chemokine receptor that is up-regulated upon maturation.
Dendritic cells (DC) that are stimulated with inflammatory mediators can maturate and migrate from nonlymphoid tissues to lymphoid organs to initiate T cell-mediated immune responses. This migratory step is closely related to the maturation of the DC. In an attempt to identify chemokine receptors that might influence migration and are selectively expressed in mature DC, we have discovered that the chemokine receptor, EBI1/CCR7, is strikingly up-regulated upon maturation in three distinct culture systems: 1) mouse bone marrow-derived DC, 2) mouse epidermal Langerhans cells, and 3) human monocyte-derived DC. The EBI1/CCR7 expressed in mature DC is functional because ELC/MIP-3beta, recently identified as a ligand of EBI1/CCR7, induces a rise in intracellular free calcium concentrations and directional migration of human monocyte-derived mature DC (HLA-DRhigh, CD1a(low), CD14-, CD25+, CD83+, and CD86high) in a dose-dependent manner, but not of immature DC (HLA-DRlow, CD1a(high), CD14-, CD25-, CD83-, and CD86-). In contrast, macrophage inflammatory protein-1alpha (MIP-1alpha), monocyte chemotactic protein-3 (MCP-3), and RANTES are active on immature DC but not on mature DC. Thus, it seems likely that MIP-1alpha, MCP-3, and RANTES can mediate the migration of immature DC located in peripheral sites, whereas ELC/MIP-3beta can direct the migration of Ag-carrying DC from peripheral inflammatory sites, where DC are stimulated to up-regulate the expression of EBI1/CCR7, to lymphoid organs. It is postulated that different chemokines and chemokine receptors are involved in DC migration in vivo, depending on the maturation state of DC.
Animals↗
Casein kinase II interacts with the bZIP domains of several transcription factors.
Casein kinase II (CKII) is thought to regulate a broad range of transcription factors, but its mode of action is not well characterized. We previously showed that CKII is co-purified with the ATF family of transcription factors using DNA-affinity latex beads. Here we report a functional and physical interaction between CKII and transcription factors. We demonstrate that CKII binds through its catalytic alpha and alpha' subunits to the basic leucine zipper (bZIP) DNA-binding domains of many transcription factors, including ATF1. Kinetic analysis using a surface plasmon resonance sensor suggests that CKII loosely associates with ATF1 in vivo . Deletion of the bZIP domain of ATF1 markedly reduces its phosphorylation by CKII, suggesting that the bZIP recruits CKII to the vicinity of the target site. ATF1-CKII complex is also formed on DNA. Using CKIIalpha fusedto a heterologous DNA-binding domain, we also demonstrate that CKII, when bound to DNA, efficiently phosphorylates its substrate, which is bound to the same DNA molecule. Taken together, CKII may regulate transcription (and possibly other events) by phosphorylating proteins on DNA.
Activating Transcription Factor 1↗
Ferrocenes as Anionic Photoinitiators.
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Journal Article↗