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T Ohkawa

Publications and source records attributed to T Ohkawa.

At least 37 records · Page 2Linked to original sources
PubMed2000

The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper 1 immune responses.

The liver remains a hematopoietic organ after birth and can produce all leukocyte lineages from resident hematopoietic stem cells. Hepatocytes produce acute phase proteins and complement in bacterial infections. Liver Kupffer cells are activated by various bacterial stimuli, including bacterial lipopolysaccharide (LPS) and bacterial superantigens, and produce interleukin (IL)-12. IL-12 and other monokines (IL- 18 etc.) produced by Kupffer cells activate liver natural killer (NK) cells and NK1.1 Ag+ T cells to produce interferon-gamma and thereby acquire cytotoxicity against tumors and microbe-infected cells. These liver leukocytes and the T helper 1 immune responses induced by them thus play a crucial role in the first line of defense against bacterial infections and hematogenous tumor metastases. However, if this defense system is inadequately activated, shock associated with multiple organ failure takes place. Activated liver NK1.1 Ag+ T cells and NK cells also cause hepatocyte injury. NK1.1 Ag+ T cells and another T-cell subset with an intermediate T-cell receptor, CD 122+CD8+ T cells, can develop independently of thymic epithelial cells. Liver NK cells and NK1.1 Ag+ T cells physiologically develop in situ from their precursors, presumably due to bacterial antigens brought from the intestine via the portal vein. NK cells activated by bacterial superantigens or LPS are also probably involved in the vascular endothelial injury in Kawasaki disease.

Animals↗
PubMed2000

Adenovirus-mediated ribozyme targeting of HER-2/neu inhibits in vivo growth of breast cancer cells.

HER-2/neu is overexpressed in 25-30% of human breast cancers. We prepared an anti-HER-2/neu hammerhead ribozyme expressed by a recombinant adenovirus (rAdHER-Rz). Human breast cancer cell lines were transduced with high efficiency, resulting in decreased HER-2/neu expression. In vivo injections of rAdHER-Rz into BT-474 tumors established in nude mice inhibited tumor growth to 20% of mock-treated controls. Similar in vivo effects were shown in MCF-7 cells, which do not overexpress HER-2/neu. The growth inhibitory effects of rAdHER-Rz were greater than those of an antisense-expressing vector. These results suggest the utility of anti-HER-2/neu ribozymes as a rational strategy for gene therapy of breast cancer. Gene Therapy (2000) 7, 241-248.

Adenoviridae↗
PubMed2000

Changes in the incidence of lower urinary tract stones in japan from 1965 to 1995.

BACKGROUND: The changes over time of the annual incidence of lower urinary tract stones in Japan from 1965 to 1995 were analyzed. METHODS: Data on lower urinary tract calculi were abstracted from the past three nationwide surveys of urolithiasis, which covered nearly all major hospitals and urologists in Japan and enumerated all outpatient visits diagnosed as urolithiasis in the years 1965, 1975, 1985 and 1995. Chronological changes in the sex- and age-related annual incidences of lower urinary tract stones and stone composition were estimated. RESULTS: Lower urinary tract stones were predominant in men 60 years of age or older. Between 1965 and 1995, the annual incidence has significantly decreased in men > or = 60 years of age from 37.2 to 27.0 per 100000 and significantly increased in women > or = 60 years of age from 2.4 to 4.8 per 100000. In men, an increased proportion of uric acid and calcium stones as well as a decreased frequency of infection stones is a phenomenon common to upper urinary tract stones. However, infection and calcium stones have been two major stone types in women. CONCLUSIONS: In contrast to upper urinary tract calculi, the incidence of lower urinary tract stones has decreased over the last 30 years in men > or = 60 years of age predisposed to this disease.

Adolescent↗
PubMed2000

Decrease of CD56(+)T cells and natural killer cells in cirrhotic livers with hepatitis C may be involved in their susceptibility to hepatocellular carcinoma.

CD56(+)T cells and CD56(+)natural killer (NK) cells are abundant in the human liver. The aim of this study was the further characterization of these cells in the liver with or without hepatitis C virus (HCV) infection. Liver mononuclear cells (MNC) were isolated from liver specimens obtained from the patients during abdominal surgery. In addition to a flow cytometric analysis, liver MNC and PBMC were cultured with the immobilized anti-CD3 Ab, IL-2, or a combination of IL-2 and IL-12 and their IFN-gamma production and the antitumor cytotoxicity were assessed. The liver MNC of HCV (-) patients contained 20% CD56(+)T cells whereas the same proportions decreased to 11% in chronic hepatitis livers and to 5% in cirrhotic livers. The proportion of NK cells also decreased in the cirrhotic livers. On the other hand, the populations of these cells in PBMC did not significantly differ among patient groups. The IFN-gamma production and the cytotoxicity against K562 cells, Raji cells, and a hepatocellular carcinoma, HuH-7 cells, greatly decreased in the cirrhotic liver MNC. In contrast, the cytotoxicity in PBMC did not significantly differ among the patient groups and was lower than that in the liver MNC of HCV (-) patients. CD56(+)T cells and NK cells but not regular T cells purified from liver MNC cultured with cytokines showed potent cytotoxicities against HuH-7 cells. These results suggest that a decreased number of CD56(+)T cells and NK cells in cirrhotic livers may be related to their susceptibility to hepatocellular carcinoma.

Aged↗
PubMed2000

[Establishment of the Japanese Radiation Oncology Study Group].

The Japanese Radiation Oncology Study Group (GROSG) which conducts multi-center trials, was organized in July, 1998 in order to establish standards' for radiation therapy. These standards must be based on the results of high quality trials, and the quality of radiotherapy must be assured in each hospital.

Clinical Trials as Topic↗
PubMed1999

Nuclear F-actin is required for AcMNPV nucleocapsid morphogenesis.

During nucleocapsid assembly, filamentous actin (F-actin) colocalizes with the major capsid protein of Autographa californica M nucleopolyhedrovirus (AcMNPV) within nuclei of infected lepidopteran host cells. Cytochalasin D (CD) disrupts actin filaments and prevents assembly of progeny AcMNPV, suggesting that nuclear F-actin is essential for nucleocapsid morphogenesis. Direct proof for this hypothesis was provided by the demonstration that two AcMNPV recombinants engineered to express either wild-type- or CD-resistant actin at equivalent rates were differentially sensitive to CD. The AcMNPV requirement for nuclear F-actin is unique among intracellular pathogens and may constitute a significant host range factor.

Actins↗
PubMed1999

Suppression of allograft rejection with anti-alphabeta T cell receptor antibody in rat corneal transplantation.

BACKGROUND: Anti-alphabeta T cell receptor monoclonal antibody (R73) has been reported to be a potent immunosuppressant. The suppressive effects of this antibody on allograft rejection after corneal transplantation are unknown. METHODS: Orthotopic rat penetrating keratoplasty was performed using Lewis rats as recipients and Brown Norway and Fisher rats as donors. The treated groups received R73 intraperitoneally until day 12 after the transplantation. In grafted rats with or without R73 treatment, cytokine expression of the aqueous humor, corneal-infiltrating cells, draining lymph nodes, and splenocytes was determined. Delayed-type hypersensitivity (DTH) responses were compared. RESULTS: All allografts in the untreated controls of Fisher-to-Lewis or BN-to-Lewis rat combinations were rejected within 14 days. In contrast, indefinite survival rates of the postoperative R73-treated group increased to 86% in the Fisher-to-Lewis and 23% in the Brown Norway-to-Lewis combinations, respectively. Interferon-y, interleukin (IL)-2 (T helper [Th]1), and IL-10 (Th2), but not IL-4 (Th2), expression of the eye and DTH responses in the control group were suppressed in the R73-treated group. Both IL-2 and IL-10 expression after mixed lymphocyte culture in the R73-treated group were significantly lower than those of the naive and untreated control group. CONCLUSIONS: alphabeta T cell receptor-targeted therapy prevents allograft rejection in rat corneal transplantation as evidenced by suppression of DTH responses. The cytokine profile after R73 treatment was characterized by low interferon-gamma, IL-2, and IL-10, and high IL-4 expression.

Animals↗
PubMed1999

A Case of Esophageal Squamous Cell Carcinoma Metastatic to the Breast.

Metastasis to the breast from extramammary malignancies is rare. There are especially few reports of metastasis from esophageal cancer. We report the pathological and autopsy findings of a 44-year-old man with advanced esophageal cancer and a left breast tumor. Squamous cell carcinoma invading the mammary glands wasdemonstrated histologically. Immunostains for ER, PgR, and ErbB-2 were negative. At autopsy, metastatic lesions were found in lung, liver, diaphragm, peritoneum, spine, and mediastinal lymph nodes, with no evidence of metastasis to the skin. While metastatic breast tumors are rarely the initial sign of malignancy, it isimportant to distinguish a metastasis from primary breast cancer to avoid unnecessary conflicting treatments.

Journal Article↗
PubMed1999

Stimulation of hyaluronan synthesis by tumor necrosis factor-alpha is mediated by the p50/p65 NF-kappa B complex in MRC-5 myofibroblasts.

The lesions of fibrocontractive diseases result from an excessive myofibroproliferative response to numerous forms of inflammatory stimuli, which elicit the net deposition of extracellular matrix (ECM) in the interstitium of the affected tissue. Hyaluronan (HA), reported to be a key player supporting cellular migration and adherence, is a major component of ECM that undergoes dynamic regulation during inflammation. The molecular regulation of HA biosynthesis by inflammatory cytokines on myofibroblasts is not yet completely understood. Here we report the biochemical characteristics of the lung myofibroblast cell line MRC-5, and we demonstrate that the production of HA by this cell line is inducible by the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), at the message level of HA synthase (HAS). In TNF-alpha-stimulated MRC-5 cells, DNA-binding and competition experiments indicated that the predominant NF-kappa B binding activity detected with nuclear extract-stimulated cells is mediated by the p50/p65 complex. Using antisense oligonucleotides, we confirmed that the TNF-alpha-stimulation of HA synthesis by MRC-5 cells is dependent on the activation of the p50/p65 NF-kappa B complex. These findings indicate that TNF-alpha production within inflamed tissues may enhance the HA synthesis via the transcriptional induction of HAS on myofibroblasts, thereby providing a provisional matrix for supporting cellular migration and adhesion, and that the p50/p65 NF-kappa B complex that plays an important role in the regulation of HA production by TNF-alpha might be an appropriate target for therapeutic compounds to treat tissue fibrosis accompanied by inflammation.

Actins↗
PubMed1999

Activation of mouse liver natural killer cells and NK1.1(+) T cells by bacterial superantigen-primed Kupffer cells.

Although bacterial superantigens have been well characterized as potent stimulators of T cells, their role in natural killer (NK)-type cells remains largely unknown. In the present study, we examined the effect of bacterial superantigens on mouse liver NK cells and NK1.1 Ag(+) (NK1(+)) T cells. C57BL/6 mice were intravenously injected with staphylococcal enterotoxin B (SEB) or streptococcal pyrogenic exotoxin A (SPE-A), and mononuclear cells (MNC) of various organs were obtained from mice 4 hours after being injected with superantigen. MNC were cultured for 48 hours, and interferon gamma (IFN-gamma) levels of supernatants were measured. The antitumor cytotoxicities of the liver and spleen MNC were also evaluated 24 hours after the mice were injected with superantigen. Liver MNC produced more IFN-gamma than did splenocytes, and peripheral blood and lung MNC did not produce any detectable IFN-gamma. In addition, liver MNC acquired a potent antitumor cytotoxicity by the SEB injection, and both NK cells and NK1(+)T cells but not cluster of differentiation (CD)8(+) T cells were responsible for the cytotoxicity as demonstrated by either in vivo or in vitro cell depletion experiments, and the NK-type cells were partly responsible for the increased serum IFN-gamma. Activation of liver NK-type cells was also supported by the fact that liver NK cells proportionally increased and NK1(+) T cells augmented their CD11a expressions after SEB injection. The pretreatment of mice with anti-IFN-gamma Ab and/or with anti-interleukin-12 (IL-12) Ab diminished the SEB-induced cytotoxicity of liver MNC. Furthermore, the in vivo depletion of Kupffer cells decreased the SEB-induced cytotoxicity of liver MNC. Consistent with these results, liver MNC stimulated with superantigens in the presence of Kupffer cells in vitro produced a greater amount of IFN-gamma than did the liver MNC without Kupffer cells or splenocytes. Our results suggest that bacterial superantigen-primed Kupffer cells produce IL-12 and other monokines, while also nonspecifically activating both NK cells and NK1(+) T cells to produce IFN-gamma.

Animals↗
PubMed1999

Hepatitis B precore mutant in children with chronic hepatitis B virus infection.

BACKGROUND: In adults, hepatitis B virus (HBV) with a G to A point mutation at nucleotide 83 in the precore region (mutant HBV 83), is commonly found in HB e antibody positive HBV carriers. It has been reported that this mutant is not able to produce HB e antigen. The exact prevalence of mutant HBV 83 in patients with chronic HBV infection is not fully understood, especially in children. METHODS: To investigate the role of mutant HBV 83 in children with chronic HBV infection, sera were tested for the presence of mutant HBV 83 using a mutation site-specific assay. RESULTS: Mutant HBV 83 was detected in 15 of 22 children (68%). Seven children were followed longitudinally, of which three were asymptomatic carriers and the other four had chronic hepatitis B on entry. There was no clear relationship between the disease activity and the presence of mutant HBV 83. CONCLUSIONS: It was concluded that mutant HBV 83 is commonly present in children with chronic HBV infection and this mutant is not necessarily associated with activation of hepatitis.

Adolescent↗
PubMed1999

The effects of human urine on the adhesion of calcium oxalate crystal to Madin-Darby canine kidney cells.

OBJECTIVE: To determine the effect of human urine on the adhesion of calcium oxalate monohydrate (COM) crystals to Madin-Darby canine kidney (MDCK) cells in a model system in vitro. MATERIALS AND METHODS: MDCK cells were exposed to COM crystals in the presence of various human urine samples. COM crystals adhering on MDCK cells were quantified by measuring the calcium concentration using atomic absorption analysis. The inhibitory activities were estimated individually for various urine samples from healthy subjects and recurrent stone formers. RESULTS: Human urine inhibited the adhesion of COM crystals to MDCK cells, with some variations between individual samples. The most potent inhibition of crystal adhesion was expressed by the macromolecular fraction of the urine. Pretreatment of crystals with human urine before exposure to the cells significantly reduced crystal adhesion, suggesting that human urine altered the properties of the crystal surface but not the cell surface. CONCLUSION: Coating of the crystals by some component(s) of human urine might be an important physiological event in preventing adhesion or retention of crystals in the renal tubules. Although the mechanisms by which crystal adhesion is prevented are unknown, a low potential for inhibiting adhesion may be a risk factor in stone formation because it permits crystal adhesion and retention in the tubules.

Animals↗
PubMed1999

National trend of the incidence of urolithiasis in Japan from 1965 to 1995.

BACKGROUND: A nationwide survey of urolithiasis in Japan was made in order to evaluate the chronological trend of upper urinary tract stones in the Japanese. It succeeded previous studies done in 1955, 1966, 1979, and 1990. METHODS: All outpatient visits to urologists that resulted in a diagnosis of first-episode upper urinary tract stones in the years 1990 and 1995 were enumerated, irrespective of admission and treatment. The study enrolled all of the Japanese Board of Urology-approved hospitals, thereby covering nearly all urologists practicing in Japan. The annual incidence by sex and age was estimated and compared with the incidences in the previous nationwide surveys. RESULTS: The age-adjusted annual incidence of first-episode upper urinary tract stones in 1995 was estimated as 68.9 per 100,000 (100.1 in men and 55.4 in women), a steady increase from 54.2 in 1965. The annual incidence has increased in all age groups, except in those of the first three decades. The peak age for both sexes has shifted in toward the older population's direction. Estimations of longitudinal changes between 1965 and 1995 showed that the annual incidence has more than doubled for the cohort of the 1965 census population (from 43.7 in 1965 to 110.9 in 1995) and that younger generations have had progressively higher annual incidences. CONCLUSIONS: The annual incidence of upper urinary tract stones in Japan has increased steadily over the past 30 years and will continue to do so in the near future, but it still is lower than in the United States.

Adolescent↗
PubMed1999

Therapeutic efficacy of an adenovirus-mediated anti-H-ras ribozyme in experimental bladder cancer.

Ras oncogenes are thought to play a critical role in cellular proliferation and tumorigenesis. Reversal of the malignant phenotype, inhibition of tumor growth, and decreased tumorgenicity have been demonstrated with the use of anti-H-ras ribozymes. In this study, the therapeutic efficacy of a hammerhead ribozyme targeting the mutated H-ras oncogene was investigated in an experimental bladder cancer model using a recombinant adenovirus as delivery vehicle. Tumors were established in nude mice by subcutaneous injection of EJ human bladder carcinoma cells harboring a point mutation of the H-ras gene. The tumors were treated with intralesional injections of an adenovirus expressing an anti-H-ras ribozyme (rAd-Hras Rz) by different schedules at serial titers, and the tumor inhibition efficacy was analyzed. The viral infection efficacy and kinetics of ribozyme expression were also evaluated. Intralesional injection of rAd-Hras Rz resulted in significant antineoplastic effects in a dose-dependent fashion. Complete regression of the tumor was achieved by rAd-Hras Rz in several cases without recurrence during the 50-day observation period. Although there was moderate vector-associated cytotoxicity in this cell line, complete regressions were not observed in the cases treated with control adenovirus vectors or vectors expressing an inactive anti-H-ras ribozyme or anti-H-ras antisense oligonucleotides. These results suggest the efficacy of a ribozyme-encoding adenovirus in the experimental gene therapy of human bladder cancer.

Adenoviridae↗
PubMed1999

Effect of fleroxacin on mouse bladder carcinogenesis with N-butyl-N- (4-hydroxybutyl) nitrosamine.

We recently reported fleroxacin significantly affected cell proliferation in a dose-dependent manner in transitional cell carcinoma cell lines. In this study, we investigated the effect of fleroxacin on mouse bladder carcinogenesis with N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN). Five-week-old C57BL/6 female mice were divided into three groups. The forced oral administrations of fleroxacin (10 or 50 mg/kg/day) were done for 1 week, then the 0.05% BHBN was given for 8 or 12 weeks. Fleroxacin treatments were continued until sacrifice. The mice were sacrificed at 4 weeks or 8 weeks latent period after BHBN administration, and the histological changes in the bladder were examined. Our study suggested that fleroxacin tended to suppress the development of bladder carcinoma or the malignant changes induced by a shorter period of BHBN administration (8 weeks) in mice. However, in the group of the BHBN administration for 12 weeks, there were no significant effects on the prevention of bladder carcinoma in both of the treatment groups with fleroxacin (10 or 50 mg/kg/day). This study did not make it clear that oral administration of fleroxacin suppressed the development of bladder carcinoma induced by BHBN in mice. However, it is very preliminary data and further experiments need to be done with a much higher dose of the fleroxacin or with other kinds of fluoroquinolone antibiotics.

Animals↗
PubMed1999

Clinical evaluation of repeat apheresis donors in Japan.

BACKGROUND AND OBJECTIVES: To ascertain the safety of repeat apheresis donation, hematological and biochemical tests were performed on 511 donors with a donation rate of over 6 times per year for a period of 12-19 months. MATERIALS AND METHODS: Repeat donors who had apheresis more than 6 times in the previous year were chosen. Data for the repeat donors at the start of the experiments were compared with those at the end of the study. Blood samples were taken prior to donation. Serum protein, albumin, immunoglobulin G, A, and M, serum ferritin levels were determined by biochemical tests. RESULTS: When compared to prospective donors of 400 ml, WBC, lymphocytes, and serum ferritin levels were lower in a roughly frequency-dependent manner in female and male donor groups at the beginning of the study. All the data for the male group remained almost constant with increasing frequency of apheresis donation. However, in the female group, ferritin levels significantly decreased with over 21 donations. CONCLUSIONS: The present data showed that the serum ferritin level of the female donors decreased the most with increasing frequency of apheresis donation. The cumulative RBC left in the collecting chamber and for the laboratory test is discussed in relation to a possible cause of iron deficiency in frequent apheresis donors.

Adult↗