Biomedical subjects
Publications and source records attributed to K Tanabe.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We have made a rat cDNA library using nerve-transected hypoglossal nuclei. Using this library, we performed expressed-sequence tag analysis coupled with in situ hybridization to identify genes whose expression is altered in response to nerve injury. In this gene screening, a member of Rho family GTPases, TC10, which had not yet been characterized in neuronal cells, was identified. TC10 mRNA expression was very low in normal motor neurons; however, axotomy induced its expression dramatically. Other family members such as RhoA, Rac1, and Cdc42 were moderately expressed in normal motor neurons and showed slight upregulation after axotomy. The expression level of TC10 mRNA was low in the embryonic brain and gradually increased with development. However, the expression of TC10 mRNA in the adult brain was lower and more restricted than that of RhoA, Rac1, and Cdc42. Cultured dorsal root ganglia exhibited dramatic neurite extension secondary to adenovirus-mediated expression of TC10. It can be concluded that although TC10 expression is lower in developing and mature motor neurons compared with other Rho family members, TC10 expression is induced by nerve injury to play a crucial role in nerve regeneration, particularly neurite elongation, in cooperation with other family members.
BACKGROUND: Sialyl Lewis(x) (CD15s), which is known to serve as a ligand for the cell adhesion molecules E-selectin and P-selectin, is expressed on peripheral lymphocytes in renal transplant patients with rejection. In this study, we examined whether CD15s monitoring could differentiate the patients with rejection in whom steroids were effective from those in whom steroids were not effective. METHODS: To investigate CD15s expression on peripheral lymphocytes, flow cytometry was performed before and after steroid pulse therapy in 20 recipients with rejection after renal transplantation, including 5 recipients resistant to steroid therapy. We also compared CD15s expression with pathological findings before and after steroid pulse therapy. RESULTS: CD15s expression was stronger before steroid pulse therapy in the 5 patients resistant to steroids than in the 15 patients responsive to steroid treatment. In addition, CD15s expression remained high without any pathological improvement in the 5 patients resistant to steroids after steroid treatment, although CD15s recovered to normal levels with remarkable improvement of pathological findings in the other 15 patients. Five patients in whom steroids were not effective, had full recovery of serum creatinine levels as well as CD15s expression after muromonab (OKT3) therapy. CONCLUSIONS: CD15s monitoring might help clinicians to select antirejection therapy.
Mitochondria of malaria parasites generate a membrane potential through an electron transport system that is a possible target of primaquine and a new anti-malarial drug, atovaquone. However, little information is available for conclusive understanding of the respiratory chain in Plasmodium mitochondria. In the present study, we cloned and characterized from Plasmodium falciparum the genes for the catalytic subunits, SDHA for the flavoprotein (Fp) and SDHB for iron-sulfur protein (Ip), of succinate-ubiquinone oxidoreductase (complex II), which is a marker enzyme for mitochondria and links the TCA cycle and respiratory chain directly. Each of the two genes contains a single open reading frame (ORF), which are located on different chromosomes, 1860 nucleotides on chromosome 10 for SDHA and 963 nucleotides on chromosome 12 for SDHB. The expression of these genes in asynchronous erythrocytic stage cells was confirmed by observation of 3.3 and 2.4 kb transcripts from the SDHA and SDHB genes, respectively. The SDHA and SDHB genes encode proteins of 620 (Fp) and 321 (Ip) amino acids with molecular masses of 69.2 and 37.8 kDa, respectively. A mitochondrial presequence essential for the import of mitochondrial proteins encoded by nuclear DNA, as well as almost all the conserved amino acids indispensable for substrate binding and the catalytic reaction were found in these peptides, indicating the functional importance of this enzyme in the parasite. Interestingly, a P. falciparum-specific insertion and a unicellular organism-specific deletion were found in the amino acid sequence of Fp. This is the first report of the primary structure of the protozoan succinate dehydrogenase.
Explore the source record for details and available documents.
BACKGROUND: In organ transplantation, the grafts must be carefully monitored, but it is often difficult to make a quick and accurate diagnosis of unusual changes. Extensive research has failed to identify a useful marker for rejection. We investigated the clinical utility of sialyl Lewis(X) (CD15s) monitoring in 17 renal transplant patients with acute rejection. METHODS: The expression of CD15s on peripheral lymphocytes was examined using flow cytometry in renal transplant recipients with rejection (n=17), without rejection (n=23), recipients infected with cytomegalovirus (n=7), recipients with other diseases (n=7), and healthy volunteers (n=18). CD15s expression was compared with histological findings, and was also examined before and after steroid pulse therapy to investigate the effects of steroids on CD15s antigen expression on the surface of the peripheral lymphocytes. RESULTS: CD15s was strongly expressed in all patients with rejection, but was not expressed in any of the patients without rejection or in any healthy volunteers. Histologically, cell infiltration into the rejected graft was moderate or severe in all patients with strong expression of CD15s. In contrast, no or only mild infiltration was observed in patients with weak expression of CD15s. In addition, 14 of 17 patients (14/17, 82%) with strong CD15s expression improved upon administration of steroid pulse therapy, although there was no benefit from steroids in any of the patients with weak expression of CD15s. CONCLUSIONS: The CD15s antigen is expressed strongly on the peripheral lymphocytes at the time of rejection. It is interesting that the efficacy of steroid therapy in the patients with elevated creatinine could be predicted by CD15s expression on the peripheral lymphocytes before graft biopsy. There have been only few reports showing the relationship between CD markers and the efficacy of the treatment in patients with elevated creatinine. We report that the detection of CD15s on the peripheral lymphocytes by flow cytometry was an easy, helpful, and noninvasive means for the diagnosis and treatment of patients with elevated creatinine after renal transplantation.
Intragenic recombination in the merozoite surface protein-1 gene (Msp-1) of Plasmodium falciparum is a major mechanism for allelic variation among natural parasite populations. The frequency of recombination depends on the intensity of transmission in the vector mosquito. In the present study, linkage disequilibrium between polymorphic 'loci' in the 5'- and 3'-regions of Msp-1 was examined in parasite populations from Brazilian Amazon and southern Vietnam and compared with that in a Thai population previously reported. The R2 test identified clusters of linkage disequilibria between the 5'- and 3'-regions, which are different among the three populations. However, the overall strength of linkage disequilibria was stronger in Brazil, a hypoendemic area, than in Vietnam and Thailand, mesoendemic areas, suggesting that linkage disequilibrium in Msp-1 inversely correlates with the intensity of transmission. To investigate possible mechanisms for linkage disequilibrium in Msp-1, we applied the Fst index, which measures the inter-population variance in allele frequency, to 'loci' in Msp-1 among the three populations. The Fst test identified two distinct regions with respect to inter-population allele frequency in Msp-1: one for highly divergent 'loci' in the 5'-region and the other for non-divergent 'loci' in the 3'-region. These results suggest that genetic drift is not the sole mechanism for linkage disequilibrium, but selection operates on 'loci' in the 3'-region in hypo- and mesoendemic areas of malaria.
Explore the source record for details and available documents.
We analyzed the relationships between levels of antibody specific for merozoite surface glycoprotein-1 (MSP1) of Plasmodium falciparum and clinical manifestations in humans. We prepared recombinant MSP1 proteins representing block 3 (M3), block 6 (M6), blocks 1-6 (M1/6), and block 17. When we divided the slide-positive individuals in Guadalcanal into symptomatic and asymptomatic groups, the former group showed lower IgG levels against M6 and block 17, but not against M3, than did the asymptomatic group (P < 0.01). The possibility of nonspecific suppression was unlikely, given that the levels of antibody against poliomyelitis virus observed in the two groups were almost the same. Among the IgG subclasses tested, production of cytophilic IgG3 seemed to be dominant. When we analyzed epitopes recognized by antibodies against block 17, a peptide (SSSNFLGIS) was preferentially recognized by sera from asymptomatic individuals. These results suggest that clinical symptoms occurring during falciparum malaria seem to be associated with the development of levels of antibody against particular epitopes on MSP1, which is under the control of an immunoregulatory mechanism.
We have performed ten pediatric kidney transplantations from living-related ABO-incompatible donors. All patients underwent preoperative plasmapheresis with or without immunoadsorption to reduce isoagglutinin. Primary immunosuppression consisted of methyl-prednisolone, cyclosporin or tacrolimus, azathioprine, anti-lymphocyte globulin, and/or deoxyspergualin. At transplantation splenectomy was simultaneously performed in all patients. Median follow-up is 65 months (range 4-95 months). The patient and graft survival rates are 100% to date. Post-transplantation isoagglutinin titers did not increase more than 1:32, except for 1 patient, without uncontrollable vascular rejection episodes. Despite the heavy immunosuppressive regimen, cytomegalovirus infection occurred in only three patients, who were successfully treated with ganciclovir and cytomegalovirus high-titer gamma globulin. Our small series clearly shows that the preoperative reduction of isoagglutinin, splenectomy, and strict immunosuppressive therapy lead to successful long-term results in children.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.