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Biomedical subjects

S Yokota

Publications and source records attributed to S Yokota.

At least 91 records · Page 5Linked to original sources
PubMed2000

Signal through gp130 activated by soluble interleukin (IL)-6 receptor (R) and IL-6 or IL-6R/IL-6 fusion protein enhances ex vivo expansion of human peripheral blood-derived hematopoietic progenitors.

This study was designed to investigate the effects of a combination of soluble interleukin (sIL)-6 receptor (R) and IL-6 on the ex vivo expansion of human peripheral blood (PB)-derived hematopoietic progenitor cells in a short-term serum-free liquid suspension culture system, using PB-derived CD34(+)IL-6R(+/-) cells as a target. In combination with stem cell factor (SCF), IL-3, and sIL-6R/IL-6, the expansion efficiency (EE) for granulocyte/macrophage colony-forming unit (CFU-GM) reached a peak level on day 10 of incubation. On the other hand, the EE for erythroid burst (BFU-E) and mixed colony-forming unit (CFU-Mix) reached a peak level on day 7 of incubation. Among the cytokine combinations tested, SCF + IL-3 + sIL-6R/IL-6 + flt3 ligand (FL) most effectively expanded CFU-GM and CFU-Mix. The maximum EEs for CFU-GM and CFU-Mix were 208-fold and 42-fold, respectively. While the EE for BFU-E was 70-90-fold in the presence of SCF + IL-3 + sIL-6R/IL-6, FL significantly augmented the EE for CFU-GM and CFU-Mix. In contrast, thrombopoietin (TPO) significantly augmented the EE for CFU-Mix. Interestingly, in combination with IL-3 and SCF, newly generated IL-6R/IL-6 fusion protein (FP) expanded PB-derived BFU-E and CFU-Mix twice more effectively than a combination of sIL-6R and IL-6. These results demonstrated that human PB-derived committed progenitors were effectively expanded in vitro using sIL-6R/IL-6 or FP, in combination with IL-3, SCF and/or FL or TPO, and that FP may transduce a stronger intracellular signal than a combination of sIL-6R and IL-6.

Animals↗
PubMed2000

[Two children with suspected primary vasculitis of mesenteric vessels--a case report].

We reported 2 children with suspected primary vasculitis of mesenteric vessels. Both children were admitted to our hospital with the complaints of abdominal pain, bloody stool or diarrhea. Laboratory examination simultaneously revealed leukocytosis with dominant neutrophils, positive CRP, and hypoalbuminemia. Although prothrombin time and activated partial thromboplastin time were within normal limits, the increased levels of FDP-E, D-dimer, and von Willebrand factor activity were observed, which suggested the endothelial cell activation and the coagulation/fibrinolysis system activation. Abdominal echography and CT scanning demonstrated the edematous thickening of intestinal or colon walls probably due to the vasculitic permeability changes of mesenteric artery. During the disease courses, skin rash, bleeding tendency, arthritis and proteinuria were not observed, and no autoantibodies including anti-nuclear antibody, anti-DNA antibody, and myeloperoxidase-antineutrophil cytoplasmic antibody, were detected. Taken together, we suspected these children as restricted vasculitis of mesenteric vessels. Intravenous prednisolone was administrated, and the clinical and laboratory abnormalities recovered completely within 2 weeks. Thus, we suggested that the leukocyte counts, CRP, and the determination of von Willebrand factor and coagulation/fibrinolysis study accompanied with X-ray, echography, and CT scanning will be useful for the early diagnosis of vasculitis before the pathologic and irreversible vascular damage are demonstrated.

C-Reactive Protein↗
PubMed2000

[Two infants with classical polyarteritis nodosa but not Kawasaki disease].

We experienced two infants with polyarteritis nodosa (PN). The symptoms started with high fever and skin rash, which were similar to those of Kawasaki disease (KD). However, the involvement of central nervous system and lung, such as distension of large fontanel, stridor and mild disturbance of consciousness, occurred and the systemic vasculitis resulted in hypoalbuminemia and severe generalized edema. They flared up twice or three times during the long clinical courses. Finally, both had multiple giant coronary aneurysms and lung fibrosis. The clinical courses of these patients were different from those of KD in that: (1) the severity of vasculitis, (2) the wide-spread nature of the vasculitis, and (3) the chronic and recurrent clinical course. It is very difficult to distinguish PN from severe KD in the early stage of the diseases especially in infancy. But in the cases intractable to high-dose gamma-globulin therapy and plasma exchange, it is needed to suspect PN and to induce more aggressive immunosuppressive therapy, such as methylprednisolone pulses and cyclophosphamide pulse therapy as soon as possible.

Cyclophosphamide↗
PubMed2000

[Molecular analysis of pathogens of upper respiratory tract infections in children--a study of nasopharyngeal S. pneumoniae and PBP genes in acute otitis media].

We have recently been confronted with refractory upper respiratory infections with an increasing prevalence of penicillin (Pc)-resistant S. pneumoniae. There has been a broad consensus that acute otitis media (AOM) is caused by migration of pathogens from nasopharynx and proliferation in the middle ear space, and thus it is, very important to study the bacterial environment in the nasopharynx as the source of middle ear infections. Eighty pneumococcal isolates from the nasopharynx of children with acute otitis media were evaluated by polymerase chain reaction (PCR) for mutation of Pc-binding protein (PBP) genes. The results showed mutation of all three PBP genes, pbp 1a, pbp 2x, and pbp 2b, in 30% of the isolates, while 74% were found to possess various PBP gene mutations, mostly in one-year-old children. Of the 46 isolates whose minimum inhibitory concentration (MIC) of Pc was < or = 0.06 microgram/mL, 43% were found to possess a pbp 2x mutaion, which affects cefem resistance. We genotyped each pneumococcal isolate from the nasopharynx of children with recurrent AOM by pulsed-field gel electrophoresis (PFGE). In 9 of 11 pairs (82%) of consecutive AOM episodes, the nasopharyngeal isolate in the second episode was different. In addition, discrimination of each isolate based upon the mutation profile of its PBP genes in 8 pairs (72%) of consecutive AOM episodes showed that the isolates were different, and there was little difference between the results of PBP gene mutation and PFGE analysis. These findings suggest that most nasopharyngeal isolates from children with AOM possess PBP mutations and that children with increased numbers of drug-resistant bacteria in their nasopharynx during AOM has been colonized or recolonized by different strains during each episode. We therefore emphasize that clinicians should assess the antibiotic susceptibility of nasopharyngeal isolates from children during each episode. PBP gene mutation analysis of S. pneumoniae is useful not only in providing valuable information on the antibiotic susceptibility of each strain but for assessing changes in causative strains in the sequential episodes of pneumococcal infection.

Acute Disease↗
PubMed2000

Slow N-acetyltransferase 2 genotype affects the incidence of isoniazid and rifampicin-induced hepatotoxicity.

SETTING: Japanese in-patients with pulmonary tuberculosis and normal liver function receiving treatment with isoniazid and rifampicin (INH + RMP). OBJECTIVE: To elucidate the relationship between N-acetyltransferase 2 (NAT2) genotype and the incidence of isoniazid + rifampicin-induced hepatotoxicity. DESIGN: Prospective study. After NAT2* genotyping, 77 patients were classified into three groups according to their NAT2* genotypes: rapid-type (a homozygote of NAT2*4), intermediate-type (a heterozygote of NAT2*4 and mutant alleles) and slow-type (a combination of mutant alleles). Their biochemical profiles of liver function test were investigated for 3 months to assess the development of serum aminotransferase elevation. RESULT: Of the 77 patients, 18.2% developed adverse hepatic reaction within the first month of INH + RMP treatment. A significant association was observed between hepatotoxicity and NAT2* genotype: compared with rapid-type, the relative risk was 4.0 (95% CI 1.94-6.06) for intermediate-type and 28.0 (95%CI 26.0-30.0) for slow-type. Especially in slow-type, the incidence of hepatotoxicity and serum aminotransferase elevation was significantly higher than in the other two types. CONCLUSION: Slow NAT2* genotype significantly affected the development of INH + RMP-induced hepatotoxicity. This suggests the possibility that NAT2* genotyping prior to medication may be useful in evaluating patients with high risk for INH + RMP-induced hepatotoxicity.

Adult↗
PubMed2000

[A case of collapsing variant of FSGS].

We report a case of collapsing variant of FSGS. An 82-year-old man without HIV-1 infection or a history of intravenous drug abuse was admitted to our hospital with the chief complaints of acute onset of generalized edema and loss of appetite. Laboratory findings were consistent with nephrotic syndrome. He developed acute renal insufficiency. Initially, we suspected minimal change nephrotic syndrome and started steroid pulse therapy but the nephrotic syndrome was refractory and a renal biopsy was performed. The pathologic findings were judged to be consistent with a collapsing variant of focal segmental glomerulosclerosis (FSGS). This form was described by Weiss et al. in 1986 as a clinically and pathologically distinct variant of FSGS. Valeri et al. further reported that the incidence of this idiopathic collapsing type of FSGS which is devoid of evidence of HIV-1 infection or intravenous drug abuse has progressively increased over the past two decades. They reported that cyclosporin is effective for the treatment of this type of FSGS with a remission rate of about 30%. The present case also had a nearly complete remission after 2 month-cyclosporin treatment. In Japan, no adult case of this type of FSGS has been reported according to our review of the literature.

Aged↗
PubMed2000

[Efficacy of patient-controlled epidural analgesia using a disposable PCA device].

We evaluated efficacy of patient-controlled epidural analgesia (PCEA) using a disposable PCA device (3.0 ml type). Twenty-two patients for elective gynecological surgery were randomized into two groups. Patients of the continuous epidural group received epidural fentanyl (15 micrograms.ml-1) with bupivacaine (1.25 mg.ml-1) from a disposable infusion pump (infusion rate: 2.1 ml.hr-1). Patients of the PCEA group received the same anesthetic solution from the same infusion pump serially connected to the disposable PCA device. There were no significant differences in postoperative visual analogue scale (VAS) scores at rest and with movement between the two groups. However, VAS scores significantly decreased from 6.8 +/- 1.6 to 1.0 +/- 1.3 when the PCA device was used for severe pain. This suggests that segmental analgesic effect might be obtained by diffusion of anesthetic solution in the epidural space after 3.0 ml PCEA bolus administration. The incidences of side effects were similar in both groups. Respiratory depression and sedative effects were not observed in both groups. We conclude that PCEA using a disposable PCA device (3.0 ml type) seems to be effective for postoperative pain relief.

Adult↗
PubMed1999

Two types of aggregate in the cerebral cortex of a seizure-sensitive strain of the Mongolian gerbil.

A 70-kDa protein, P70, found mostly in the pyramidal cells of the cerebral cortex of cobalt-induced epileptogenic rats, has been implicated in epileptogenesis. The presence of a P70-like substance was searched for immunohistochemically in the cerebral cortex of MGS/ldr, a seizure-sensitive strain of the Mongolian gerbil (Meriones unguiculatus) that we previously established. Immunoreactive aggregates were observed in the pyramidal neurons of the motor cortex and the primary somatosensory cortex. Analysis using confocal laser scanning microscopy revealed that the aggregates were often colocalized with a second type of aggregate with red autofluorescence at the marginal zone of the cell somata. Both aggregates appeared and increased before the appearance of generalized tonic-clonic convulsion. These may be involved in some change of physiological function of the cerebral cortex but their presence itself is not enough to determine the occurrence of epileptic seizure because the gerbils that showed no such seizure had both aggregates.

Animals↗
PubMed1999

Cytosolic chaperonin is up-regulated during cell growth. Preferential expression and binding to tubulin at G(1)/S transition through early S phase.

The chaperonin containing t-complex polypeptide 1 (CCT) is a heterooligomeric molecular chaperone assisting in the folding of actin, tubulin, and other cytosolic proteins. The expression levels of CCT subunits varied among seven mouse cell lines tested but showed a close correlation with growth rate. Both the CCT protein and mRNA levels in the human promyelolytic cell HL60 decreased concomitant with growth arrest during differentiation. More rapid decrease in CCT level occurred when the mouse interleukin (IL)-3-dependent myeloid DA3 cells were starved for IL-3. Readdition of IL-3 caused rapid resumption of CCT synthesis during synchronous growth: the maximum CCT protein and mRNA levels were observed at G(1)/S transition through early S phase. The turnover rate of CCT was nearly constant regardless of growth. Gel filtration and immunoprecipitation analyses indicated that CCT in vivo is associated with tubulin at early S phase, but not at G(0)/G(1) phase. These results demonstrated that CCT expression is strongly up-regulated during cell growth especially from G(1)/S transition to early S phase and is primarily controlled at the mRNA level. CCT appears to play important roles for cell growth by assisting in the folding of tubulin and other proteins.

Animals↗
PubMed1999

Development of macroglial cells in the embryonic chick optic nerve.

Macroglia development in the embryonic chick optic nerve was immunohistochemically examined. The astrocytes with glial fibrillary acidic protein immunoreactivity were initially restricted to the retinal end of the optic nerve at stage 40, but had widely dispersed within the optic nerve in an out-side-in manner by stage 44. Oligodendrocytes with myelin basic protein immunoreactivity appeared at stage 38, and were widely distributed at stage 40. Electron microscopic observation confirmed the presence of intermediate filaments in the glial fibers and developing myelin at stages 40-41. The present results suggest that oligodendrocyte precursors undergo terminal differentiation slightly earlier than astrocyte precursors with respect to the expression of marker proteins.

Animals↗
PubMed1999

Transcriptional activation of mouse cytosolic chaperonin CCT subunit genes by heat shock factors HSF1 and HSF2.

The chaperonin containing TCP-1 (CCT) is a eukaryotic molecular chaperone consisting of eight subunit species and assists in the folding of cytosolic proteins. We show here that all eight mouse CCT subunit genes contain sequences called heat shock elements for binding heat shock transcription factors (HSFs) by electrophoretic mobility shift assays and that these genes are transcriptionally activated by HSFs in reporter gene assays using HeLa cells transiently overexpressing HSFs. These results suggest that HSF1 and/or HSF2 play a role in Cct gene expression.

Animals↗
PubMed1999

Lipid-binding and antimicrobial properties of synthetic peptides of bovine apolipoprotein A-II.

We previously showed that bovine apolipoprotein A-II (apoA-II) had antimicrobial activity against Escherichia coli and the yeast Saccharomyces cerevisiae in PBS. We have characterized here the active domain of apoA-II using synthetic peptides. A peptide corresponding to C-terminal residues Leu(49)-Thr(76) exhibited significant antimicrobial activity against E. coli in PBS, but not against S. cerevisiae. Experiments using amino-acid-substituted peptides indicated that the residues Phe(52)-Phe(53)-Lys(54)-Lys(55) are required for the activity. Peptide Leu(49)-Thr(76) induced the release of calcein trapped inside the vesicles whose lipid composition resembles that of E. coli membrane, suggesting that peptide Leu(49)-Thr(76) can destabilize the E. coli membrane. CD measurements showed that the alpha-helicity of peptide Leu(49)-Thr(76) increased from 3.5 to 36% by addition of the vesicles. When E. coli cells were incubated with peptide Leu(49)-Thr(76), some proteins were released to the external medium, probably owing to membrane destabilization caused by the peptide. In electron micrographs of E. coli cells treated with peptide Leu(49)-Thr(76), transparent nucleoids and granulated cytoplasm were observed. Amino acid substitutions, Phe(52)Phe(53)-->AlaAla (Phe(52, 53)-->Ala) in peptide Leu(49)-Thr(76) caused the loss of antimicrobial activity against E. coli, although protein-releasing activity was retained. Electron micrographs of the cells treated with peptide Leu(49)-Thr(76)(Phe(52,53)-->Ala) revealed morphological change only at the nucleoids. Therefore peptide Leu(49)-Thr(76) appears to primarily target the cytoplasm rather than the membrane of E. coli cells.

Amino Acid Sequence↗
PubMed1999

Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia.

Internal tandem duplication of the FLT3 gene and point mutations of the N-RAS gene are the most frequent somatic mutations causing aberrant signal-transduction in acute myeloid leukemia (AML). However, their prognostic importance is unclear. In this study, their prognostic significance was analyzed in 201 newly diagnosed patients with de novo AML except acute promyelocytic leukemia. Three patients had mutations in both genes, 43 had only the FLT3 gene mutation, 25 had only the N-RAS gene mutation, and 130 had neither. These mutations seemed to occur independently. Both mutations were related to high peripheral white blood cell counts, and the FLT3 gene mutation was infrequently observed in the French-American-British (FAB)-M2 type. AML cases with wild FLT3/mutant N-RAS had a lower complete remission (CR) rate than those with wild FLT3/wild N-RAS, whereas the presence of mutant FLT3 did not affect the CR rate. Univariate analysis showed that unfavorable prognostic factors for overall survival were age 60 years or older (P =.0002), cytogenetic data (P =.002), FAB types other than M2 (P =.002), leukocytosis over 100 +/- 10(9)/L (P =.003), and the FLT3 gene mutation (P =.004). However, the N-RAS gene mutation was only a marginal prognostic factor (P =.06). For the subjects under 60 years old, multivariate analysis showed that the FLT3 gene mutation was the strongest prognostic factor (P =.008) for overall survival. The FLT3 gene mutation, whose presence is detectable only by genomic polymerase chain reaction amplification and gel electrophoresis, might serve as an important molecular marker to predict the prognosis of patients with AML.

Acute Disease↗
PubMed1999

Characterization of the 70-kDa peroxisomal membrane protein, an ATP binding cassette transporter.

The 70-kDa peroxisomal membrane protein (PMP70) is one of the major components of rat liver peroxisomal membranes and belongs to a superfamily of proteins known as ATP binding cassette transporters. PMP70 is markedly induced by administration of hypolipidemic agents in parallel with peroxisome proliferation and induction of peroxisomal fatty acid beta-oxidation enzymes. To characterize the role of PMP70 in biogenesis and function of peroxisomes, we transfected the cDNA of rat PMP70 into Chinese hamster ovary cells and established cell lines stably expressing PMP70. The content of PMP70 in the transfectants increased about 5-fold when compared with the control cells. A subcellular fractionation study showed that overexpressed PMP70 was enriched in peroxisomes. This peroxisomal localization was confirmed by immunofluorescence and immunoelectron microscopy. The number of immuno-gold particles corresponding to PMP70 on peroxisomes increased markedly in the transfectants, but the size and the number of peroxisomes were essentially the same in both the transfectants and the control cells. beta-Oxidation of palmitic acid increased about 2-3-fold in the transfectants, whereas the oxidation of lignoceric acid decreased about 30-40%. When intact peroxisomes prepared from both the cell lines were incubated with palmitoyl-CoA, oxidation was stimulated with ATP, but the degree of the stimulation was higher in the transfectants than in the control cells. Furthermore, we established three Chinese hamster ovary cell lines stably expressing mutant PMP70. In these cells, beta-oxidation of palmitic acid decreased markedly. These results suggest that PMP70 is involved in metabolic transport of long chain acyl-CoA across peroxisomal membranes and that increase of PMP70 is not associated with proliferation of peroxisomes.

ATP-Binding Cassette Transporters↗
PubMed1999

In situ determination of proportion of cell types in wood by Fourier transform Raman spectroscopy.

Analysis of the proportion of cell types in native wood is important for understanding the environmental stresses including an increasing atmospheric CO2 concentration on the structure of wood, especially for the management of plantation forests which will reduce our reliance on natural forests. The conventional method for determining the proportion of cell types is a quantitative microscopy, which is one of the image analyzing systems using a light microscope combined with a microcomputer. However, it is a lengthy multistep procedure. We have examined the feasibility of using Fourier transform Raman spectroscopy for rapid determination of proportion of cell types (fiber, ray parenchyma, vessels, and axial parenchyma) in native wood with using wood meals of two Eucalyptus species, including samples of various ages and colors. By the application of second derivative transformation of Raman spectroscopic data and the partial least-squares regression, we have successfully obtained highly significant correlations between microscopically measured and Raman predicted values for all traits except vessels with correlation coefficients of >0.9 and 0.8, respectively, in the calibration and in the prediction. This method is valid for all traits since vessels can be calculated by the rest of three traits, and will help to solve the effect of the environmental issues on trees and the supplement of renewable raw materials.

Cell Lineage↗
PubMed1999

Identification of a genetic risk factor for systemic juvenile rheumatoid arthritis in the 5'-flanking region of the TNFalpha gene and HLA genes.

OBJECTIVE: To study polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor alpha (TNFalpha) gene and in the coding regions of HLA class I and class II genes, in order to better understand the genetic background of juvenile rheumatoid arthritis (JRA). METHODS: One hundred eleven Japanese JRA patients (50 with systemic disease, 29 with pauciarticular disease, and 32 with polyarticular disease) and 575 healthy Japanese subjects were examined for the allele frequencies of the TNFalpha, HLA-A, and HLA class II (DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1) genes, by DNA typing using the polymerase chain reaction-sequence-specific oligonucleotide probe method. RESULTS: The frequencies of the polymorphic allele at positions -1,031 (T to C substitution, termed -1,031C), -863 (C to A, termed -863A), and -857 (C to T, termed -857T) of the TNFalpha gene in patients with systemic JRA, but not in those with polyarticular or pauciarticular JRA, were significantly higher than in the healthy controls. The allele frequencies of DRB1*0405 and DQB1*0401 in systemic JRA, but not in the other JRA types, were significantly higher than in controls. Linkage analysis showed that the presence of both the TNFalpha -857T allele and DRB1*0405 yielded a significantly increased odds ratio (3.84), while the presence of only 1 of them did not yield a high odds ratio (0.87 and 1.58). CONCLUSION: The -1,031C/-863A allele and the -857T allele of the TNFalpha gene, both of which are related to high production of tumor necrosis factor alpha, are associated with systemic JRA. The -857T allele may enhance the effect of the DRB1*0405/DQB1*0401 haplotype in predisposing to development of systemic JRA.

Arthritis, Juvenile↗