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H Okada

Publications and source records attributed to H Okada.

At least 145 records · Page 8Linked to original sources
PubMed2000

Alternative exon usage in the 3' region of a single gene generates glycosylphosphatidylinositol-anchored and transmembrane forms of rat decay-accelerating factor.

Several cDNA clones encoding genetic homologues of human decay-accelerating factor (DAF) were isolated from rat testis cDNA libraries and reverse transcription-polymerase chain reaction products. Sequence analysis revealed that rat DAF exists as two membrane forms, a glycosylphosphatidylinositol (GPI)-anchored and a transmembrane (TM) form. Southern blotting analysis showed that GPI- and TM-form mRNAs of rat DAF are derived from a single gene, as is the case for guinea pig, though both forms of mouse DAF mRNA are derived from two genes. Gene analysis of the C-terminal region of rat DAF indicated that both forms of mRNA are presumably generated by alternative splicing of exons which encode a GPI/3'-untranslated (3'UT) region and a TM/3'UT region in the 3' end of the Ser/Thr-rich region. Northern blot analysis indicated that rat GPI-DAF mRNA was present in all tissues examined except for liver, while rat TM-DAF mRNA was preferentially expressed in testis. Infant rat testis barely expressed TM-DAF and membrane cofactor protein (MCP) but highly expressed 5I2 antigen (5I2Ag, rat Crry). However, adult rat testis showed increased expression of the 1.6-kb transcript of rat GPI-DAF, TM-DAF, MCP, and the 0.7-kb transcript of CD59, with a decreased level of 5I2Ag expression. These results suggest that rat 5I2Ag/Crry may play an important role in regulating complement activation during the early stages of testis development, and that DAF, MCP, and CD59 expressed in testis may enable sperm to survive complement attack in the mucus of the female genital organ, and/or to interact with an ovum.

3' Untranslated Regions↗
PubMed2000

Regulation of xyn3 gene expression in Trichoderma reesei PC-3-7.

The characteristics of regulation of the gene encoding the third xylanase (Xyn III) of a filamentous fungus, Trichoderma reesei PC-3-7, were studied by Northern blot analysis. A partial DNA sequence (185 bp) of the xyn3 gene was obtained by PCR amplification of genomic DNA of T. reesei PC-3-7 and sequenced. This xyn3 gene fragment was used as a probe for Southern and Northern blot analysis. The expression of the xyn3 gene was regulated at the transcriptional level. The xyn3 mRNA was expressed in mycelia of T. reesei PC-3-7 induced by Avicel, L-sorbose and sophorose, but not by xylose, xylooligosaccharides and birchwood xylan. Furthermore, it was observed that xyn3 was synchronously expressed with egll but not with xyn1 and xyn2 by L-sorbose, indicating that the xyn3 gene may be coordinately expressed with cellulase genes. By Southern blot analysis, the xyn3 gene was confirmed to exist as a single copy in both strains of T. reesei PC-3-7 and QM9414. However, no xyn3 mRNA appeared in the mycelia induced by any kind of inducers in T. reesei QM9414 even when total RNA was used in large excess, suggesting that the xyn3 gene in T. reesei QM9414 is in the dormant state and cannot be expressed. Therefore, T. reesei PC-3-7 may be a very useful strain for elucidating the induction mechanism of xylanase biosynthesis by cellulosic and xylanosic substrates, and also the regulatory correlation between cellulase and xylanase induction.

Amino Acid Sequence↗
PubMed2000

Short dynamic FDG-PET imaging protocol for patients with lung cancer.

This positron emission tomography (PET) study was designed to compare 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) kinetic parameters of tumours derived from imaging frames of 0-60 min post FDG injection with those derived from shorter imaging frames of 0-30 min. Dynamic FDG-PET scans were performed on 20 patients with primary lung cancers for 1 h after intravenous injection of FDG. Images were reconstructed with attenuation correction using transmission images obtained with a germanium-68 ring source immediately before FDG injection. A region of interest (ROI) was placed on the plane of the maximal tumour FDG uptake. Arterial input function was estimated from an ROI defined in the left atrium. Based on the standard three-compartment metabolic model, we calculated the rate constants (K1-k3) and influx constant Ki = K1k3/(k2+k3) using the imaging frames for 60 min and 30 min post FDG injection. The standardized uptake value (SUV) of tumour was measured using the imaging frame of 50-60 min post injection. High correlations were observed between kinetic parameters (K1, k2, k3 and Ki) derived from imaging frames of 0-60 min and 0-30 min [0.231+/-0.114 vs 0.260+/-0.174 (r=0.958), 1.149+/-1.038 vs 1.565+/-2.027 (r=0.968), 0.259+/-0.154 vs 0.311+/-0.194 (r=0.886) and 0.044+/-0.022 vs 0.048+/-0.023 (r=0.961), respectively, P<0.001]. Ki showed an excellent agreement between the two methods (y=-0.0041+0.9831x). Mean SUV of the lung cancers was 6.58+/-2.85. It is concluded that the briefer 30-min acquisition may yield essentially the same results as the standard 60-min imaging protocol, thus offering a time saving in dynamic PET studies in which the model parameters are desired.

Adenocarcinoma↗
PubMed2000

Extensive lymphopenia due to apoptosis of uninfected lymphocytes in acute measles patients.

Infection with measles virus induces a transient immunosuppression, which occasionally results in fatal opportunistic infections. To obtain fundamental information about the mechanism, we examined peripheral blood mononuclear cells (PBMC) from acute measles patients aged from infants to 35 years old, obtained at various times from incubation periods to 103 days after onset of rash, for the number of lymphocyte subsets by flowcytometry. The data were analyzed for relationships between aging of the patients and the severity of immunosuppression. In classical measles cases, infected lymphocytes detected as a minor population during the incubation period disappeared soon after onset of rash, whereas in the cases of serious illness, the infected cells persisted longer after the rash. At the onset of rash, remarkable lymphopenia had already occurred in all measles cases with reduction in cell numbers of CD4+ T cells, CD8+ T cells, B cells, neutrophils, and monocytes. In contrast, natural killer (NK) cells were increased in number and activated, which might be a response compensatory for the lymphopenia. Apoptosis-associated molecules such as CD95(Fas) and TNF-related apoptosis-inducing ligand-receptor (TRAIL-R) were highly expressed on the cell surface of most surviving non-infected lymphocytes, and DNA fragmentation was also observed upon incubation in vitro. These results suggested that the profound lymphopenia was primarily due to extended death of non-infected blood cells caused by apoptosis. The severity and duration of the lumphopenia were age-dependent; less severe in young children whereas much severer in infants under one year of age as well as adolescents and adults. From these results, it was suggested that remarkable lymphopenia due to apoptosis of uninfected cells is one of the principal causes for immunosuppression induced by measles virus infection, and is correlated with the age-dependent severity of the disease.

Acute Disease↗
PubMed2000

Health-related quality of life with orthotopic neobladder versus ileal conduit according to the SF-36 survey.

OBJECTIVES: To compare health-related quality of life (HRQOL) in patients with a neobladder and in patients with an ileal conduit. METHODS: HRQOL was assessed using the SF-36 survey, supplemented with a questionnaire concerning micturition status. RESULTS: Patients (n = 36) with a neobladder were significantly younger at time of surgery and time of survey than patients with an ileal conduit (n = 20). Mean (+/- SD) follow-up periods for patients with a neobladder and with an ileal conduit were 31.3 +/- 33.1 and 44.8 +/- 30.7 months, respectively. No significant difference was apparent in any scale score between neobladder and ileal conduit groups. Role-physical functioning (RP) and role-emotional functioning (RE) scale scores in both neobladder and ileal conduit patients appeared to be below the general U.S. population norm. Patients with neobladder 65 years old or older (n = 17) showed significantly lower RP and RE scores than those younger than 65 years (n = 19; P <0.05). Duration of follow-up was not related to scale scores. Continence status did not measurably affect HRQOL. CONCLUSIONS: All scales concerning HRQOL except RP and RE were favorable with both neobladder and ileal conduit, and no significant differences were observed between these two types of urinary tract reconstruction. Generally, patients with a neobladder or an ileal conduit were satisfied with their overall quality of life and health.

Aged↗
PubMed2000

Adenosine regulates the production of interleukin-6 by human gingival fibroblasts via cyclic AMP/protein kinase A pathway.

Adenosine has been reported to alter a variety functions of the cells that participate in inflammatory responses. However, the effect(s) of adenosine on human gingival fibroblasts (HGF), one of the immunomodulator cells in inflamed periodontal lesions, remains to be established. In this study, we examined the influence of adenosine on the production of interleukin (IL)-6 by HGF. Ligation of adenosine receptors with adenosine or its related analogue, 2-chloroadenosine (2-CADO), increased IL-6 production by HGF without any other stimuli. In addition, adenosine and 2-CADO enhanced the cyclic AMP (cAMP) level in HGF as did prostaglandin E1 (PGE1) and forskolin. Interestingly, these cAMP-arising reagents and the permeable cAMP analogue, dibutyryl cAMP (dbtcAMP), also increased IL-6 production by HGF. These results suggest that cAMP is involved in adenosine-induced IL-6 production by HGF. Adenosine-induced IL-6 production was suppressed by protein kinase A (PKA) inhibitor, H89, indicating that cAMP/PKA pathway is involved in the induction. Moreover, the experiments using antagonists specific for adenosine receptor subtypes revealed that the adenosine-induced IL-6 production by HGF was, at least in part, mediated by the adenosine A2b receptor. These results provide new evidence for the possible effects of adenosine or its related analogue as an immunomodulator in inflammatory periodontal lesions.

2-Chloroadenosine↗
PubMed2000

Characterization and transduction of a retroviral vector encoding human interleukin-4 and herpes simplex virus-thymidine kinase for glioma tumor vaccine therapy.

Vaccination with cytokine-transduced tumor cells represents a potentially important approach to the treatment of central nervous system tumors. We have recently demonstrated the therapeutic efficacy of tumor cell vaccines expressing the murine interleukin 4 (IL-4) and the herpes simplex virus-thymidine kinase in a rat brain tumor model in which nonirradiated vaccine cells can be eliminated by the subsequent administration of ganciclovir. In this report, we demonstrate the construction and characterization of a retroviral vector that encodes human IL-4, neomycin phosphotransferase, and herpes simplex virus-thymidine kinase genes for use in human clinical trials. An MFG-based retroviral vector was used to generate the recombinant retrovirus, TFG-hIL4-Neo-Tk, in which a long terminal repeat-driven polycistronic transcript encodes three cDNAs that are linked and coexpressed using two intervening internal ribosome entry site fragments from the encephalomyocarditis virus. The amphotropic retroviral vector TFG-hIL4-Neo-Tk was then used to infect human primary glioma cultures and skin-derived fibroblasts. After infection and G418 selection, cells produced 89-131 ng/10(6) cells/48 hours of human IL-4, which was determined to be biologically active. Transduced glioma cells were highly sensitive to the cytotoxic effect of ganciclovir. These data demonstrate the suitability of the TFG-hIL4-Neo-Tk vector for therapeutic studies of cytokine-transduced autologous tumor vaccination in patients with malignant gliomas.

Animals↗
PubMed2000

Decay accelerating factor in guinea-pig reproductive organs.

Decay accelerating factor (DAF, CD55) expressed in human reproductive organs and gametes is thought to play a pivotal role in protection against autologous complement activation in the genital tract. To further investigate the role of DAF in reproduction, we analysed DAF distribution in reproductive organs using guinea-pigs that express multiple DAF isoforms. In males, significant staining was observed in testis on the elongated spermatids and spermatozoa. Levels of DAF mRNA with a shorter 3' untranslated region were significantly enhanced in testis from 9 weeks of age, indicating the presence of DAF mRNA and protein synthesis of spermatozoa DAF in late haploid germ cells. Epididymal spermatozoa appeared to express DAF on the inner acrosomal membrane as well as over their entire surface. Significant DAF expression was also observed on the epithelium of seminal vesicles from 4 weeks of age, with no increase thereafter in the mRNA. C3 mRNA was not detected in this tissue. In females, DAF was detected on the plasma membranes of oocytes through follicle development and on the apical region of uterine epithelium, although the levels of DAF mRNA in these tissues were low. In addition, DAF was selectively expressed on the apical region of ciliated oviductal epithelial cells. The apical region of the ciliated cells comprising the efferent ductule epithelium was also stained significantly, even at 12 days of age, while other epididymal epithelial cells were hardly stained at any age, suggesting that DAF is constitutively expressed on cilia.

Animals↗
PubMed2000

A comparative study of terazosin and tamsulosin for symptomatic benign prostatic hyperplasia in Japanese patients.

OBJECTIVE: To compare the efficacy and safety of an incremental-dose regimen of terazosin (1-2 mg daily) and a fixed-dose regimen of tamsulosin (0.2 mg daily), on Japanese patients with symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: This multicentre, single-blind, randomized trial compared terazosin and tamsulosin over 4 weeks, in 61 patients with symptomatic BPH randomly assigned to terazosin (n = 31) or tamsulosin (n = 30). Terazosin 0.5 mg twice daily was administered for 2 weeks, followed by 1 mg twice daily for 2 weeks. Tamsulosin (0.2 mg) was administered once daily for 4 weeks. Symptoms were evaluated using the International Prostate Symptom Score (IPSS), and quality of life (QOL) was assessed subjectively before treatment, and again after 2 and 4 weeks of treatment. Objective measurements taken before and after the treatment period were the maximum (Qmax) and average (Qave) urinary flow rates, and the percentage residual urine volume. Improvement was defined as a 25% decrease from baseline in IPSS, > 1 point increase in QOL score, and > 2.5 mL/s increase in Qmax. Adverse reactions potentially related to the study drugs were recorded throughout the treatment period. RESULTS: Both terazosin and tamsulosin produced statistically significant improvements in subjective and objective variables. Neither treatment affected systolic or diastolic blood pressure or pulse rate. Adverse reactions were noted in four patients (three in the terazosin group and one in the tamsulosin group). However, there was no statistically significant difference in the incidence of adverse effects between the groups. CONCLUSIONS: Despite the limitations of small sample size and relatively short treatment periods, terazosin and tamsulosin were equally effective in the treatment of symptomatic BPH in Japanese patients, using relatively lower doses than those used in Western countries.

Adrenergic alpha-Antagonists↗
PubMed2000

Progressive renal fibrosis in murine polycystic kidney disease: an immunohistochemical observation.

BACKGROUND: The appearance of interstitial fibrosis in polycystic kidneys is emblematic of progressive disease. Matrix forming this scar tissue is derived from local renal cells in response to cystogenesis. We investigated the phenotype of collagen-producing cells in the cystic kidneys of DBA/2-pcy mice to better characterize the spectrum of interstitial cells associated with renal fibrogenesis. METHODS: The extent of interstitial fibrosis and the number of fibroblasts in cystic kidneys were first quantitated over time using computer-assisted image analysis. Subsequently, antisera to four cell protein markers were studied by coexpression immunohistochemistry during progression of fibrosis using confocal microscopy. The antisera included fibroblast-specific protein 1 (FSP1) for fibroblast phenotype, alpha-smooth muscle actin (alpha-SMA) for contractile phenotype, vimentin (VIM) for mesenchymal phenotype, and heat shock protein 47 (HSP47) for interstitial collagen-producing phenotype. RESULTS: Interstitial fibrosis in cystic kidneys gradually increased throughout the 30-week observation period of our study. With progression of cystogenesis, most of the tubules in pcy mice either dilated or disappeared with time. FSP1+ fibroblasts were distributed sparsely throughout the renal interstitium of young pcy and wild-type mice. Their number increased in the widening fibrotic septa by 18 weeks of age and persisted through 30 weeks of the study interval. Some epithelia among remnant tubules trapped within fibrotic septa around adjacent cysts also acquired the phenotype of FSP1+, HSP47+ collagen-producing fibroblasts, suggesting a possible role for epithelial-mesenchymal transformation (EMT) in this process. Most FSP1+ fibroblasts were alpha-SMA-, but HSP47+, suggesting they were producing collagen proteins for the extracellular matrix. alpha-SMA+, FSP1-, HSP47+ or HSP47- cells were also observed, and the latter tended to distribute independently in a linear pattern, reminiscent of vasculature adjacent to forming cysts. VIM+ expression was not observed in alpha-SMA+ cells. CONCLUSIONS: Many nonoverlapping as well as fewer overlapping populations of FSP1+ and alpha-SMA+ cells shared in the collagen expression associated with progressive fibrogenesis in pcy mice undergoing cystogenesis. Some FSP1+ fibroblasts are likely derived from tubular epithelium undergoing EMT, while alphaSMA+, VIM- cells probably represent vascular smooth muscle cells or pericytes surviving vessel attenuation during the chaos of fibrogenesis. Importantly, not all interstitial cells producing collagens are alpha-SMA+.

Actins↗
PubMed2000

CD59 protects rat kidney from complement mediated injury in collaboration with crry.

BACKGROUND: As previously reported, the membrane-bound complement regulator at the C3 level (Crry/p65) is important in maintaining normal integrity of the kidney in rats. However, the role of a complement regulator at the C8/9 level (CD59) is not clear, especially when activation of complement occurs at the C3 level. The aim of this work was to elucidate the in vivo role of CD59 under C3 activating conditions. METHODS: Two monoclonal antibodies, 5I2 and 6D1, were used to suppress the function of Crry and CD59, respectively. In order to activate alternative the pathway of complement, the left kidney was perfused with 5I2 and/or 6D1 and was recirculated. RESULTS: In the kidneys perfused with 5I2 alone, deposition of C3 and membrane attack complex (MAC) was observed in the peritubular capillaries, vasa recta, and tubular basement membranes. Cast formation, tubular dilation and degeneration, and cellular infiltration were observed at days 1 and 4, and they recovered by day 7. Further suppression of CD59 by 6D1 significantly enhanced the deposition of MAC and worsened the already exacerbated tubulointerstitial injury. These effects of 6D1 were dose dependent. Perfusion with 6D1 alone did not induce histologic damage or MAC deposition in the tubulointerstitium. CONCLUSIONS: In rats, CD59 maintains normal integrity of the kidney in collaboration with Crry in rats against complement-mediated damage in vivo.

Animals↗
PubMed2000

Inhibition of monocyte chemoattractant protein-1 expression in tubular epithelium attenuates tubulointerstitial alteration in rat Goodpasture syndrome.

BACKGROUND: To examine the role of monocyte chemoattractant protein-1 (MCP-1) expressed by tubular epithelium in tubulointerstitial alterations in situ, the level of MCP-1 mRNA in tubular epithelium was lowered selectively in the rat model of Goodpasture syndrome (GPS). METHODS: Intravenously administered antisense oligodeoxynucleotide (ODN) is taken up by renal tubular epithelium and has been found to block expression of target genes in rats. MCP-1 antisense ODN was injected into GPS rats every second day from days 27 to 35 after immunization (this represents the time when renal MCP-1 mRNA level was increased and interstitial mononuclear cell infiltration was aggravated). RESULTS: In addition to a reduction in the level of tubular MCP-1 mRNA, antisense ODN treatment attenuated monocyte infiltration significantly and preserved renal function in GPS rats. However, ODN injection did not affect glomerular MCP-1 expression and glomerular histopathology, and there were no significant changes in the urinary protein excretion rate. CONCLUSION: Our findings provide direct evidence that MCP-1, expressed by tubular epithelium, plays a pivotal role in mediating secondary tubulointerstitial alterations in the GPS model.

Animals↗
PubMed2000

Tubular osteopontin expression in human glomerulonephritis and renal vasculitis.

Tubulointerstitial change is a common histopathologic feature of acute and chronic glomerular diseases and is more closely correlated than glomerular damage with renal function and subsequent outcome. Monocyte infiltration is presumed to be initiated by chemoattractants and has a pivotal role in tubulointerstitial changes. Osteopontin (OPN) is a candidate as such a chemoattractant and has been shown to recruit monocytes into the interstitium of animal models of renal diseases. In this study, we investigated OPN expression by immunostaining and its correlation with clinical and histopathologic parameters in patients with immunoglobulin A (IgA) nephropathy, diffuse proliferative lupus nephritis (DPLN), and myeloperoxidase-antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis (MMP). Twenty patients with IgA nephropathy, 12 patients with DPLN, and 14 patients with MMP were studied. OPN expression, which was constitutively observed on the apical membrane of distal tubules, was upregulated in the cytoplasm of proximal and distal tubular epithelium parallel to the degree of interstitial mononuclear cell infiltration in patients with IgA nephropathy, as well as those with DPLN. CD68(+) monocyte infiltration significantly correlated with the degree of OPN expression in the tubular epithelium. Conversely, there was no apparent induction of OPN in the proximal and distal tubular epithelium of patients with MMP despite remarkable monocyte infiltration. In conclusion, these data suggest that inducible expression of OPN in the tubular epithelium seems to be associated with interstitial monocyte infiltration and subsequent tubulointerstitial changes in some forms of human renal diseases.

Biopsy↗
PubMed2000

Exploitation of immune mechanisms in the treatment of central nervous system cancer.

Malignant gliomas are among the most common intrinsic brain tumors of both children and adults, and, because of unique aspects of their biology and anatomic site, they are the most refractory to conventional therapeutic strategies involving surgery, radiotherapy, or chemotherapy. Given the failure of standard therapies to improve the outlook of affected patients, significant attention has been focused on development of alternative treatments, particularly immunotherapy. Attempts have been made to treat gliomas using a variety of immunologically based strategies, including passive immunization, adoptive cellular immunotherapy, local and systemic delivery of biological response modifiers, and vaccination with tumor cells. Although preclinical modeling of these therapies provided an impetus for translation of their results into clinical protocols, these therapies have failed to yield consistently promising results in initial trials. However, significant insights into the immunobiology of the central nervous system (CNS) and gliomas have been gained from these studies, and have established that a number of immunobiological features of the brain and of gliomas themselves may be critical determinants in regulating efficacious treatment of these tumors. These include the following: (1) the presence of a blood-brain barrier that, although partially disrupted by the tumor, functions to exclude elements of the immune system from the tumor or brain parenchyma; (2) a lack of organized secondary lymphatic tissues supporting efficient immune responses locally in the CNS; (3) low levels of expression of major histocompatibility complex proteins in the CNS; (4) an apparent paucity of the most efficient antigen-presenting cells; and (5) glioma-derived immunosuppressive factors, such as transforming growth factor-beta, that interfere with the induction of local as well as systemic immune responses to the tumor. Recognition of these factors, and an appreciation of the underlying need for and validity of developing immunologically based therapies for gliomas, supports continued development of novel immunotherapeutic approaches, particularly those attempting to enhance the immunogenicity of glioma cells. This review addresses the current state of knowledge regarding the immunobiology of gliomas, recent developments in immunotherapy of gliomas, and promising future directions for development and implementation of cellular immunotherapy of gliomas.

Adult↗