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Biomedical subjects

F Nishikawa

Publications and source records attributed to F Nishikawa.

At least 55 records · Page 3Linked to original sources
PubMed1992

Mononuclear cell response in the liver of mice infected with hepatotoxigenic Campylobacter jejuni.

Intragastric inoculation with hepatotoxigenic strains of Campylobacter jejuni led to the death of mice during the late phase of infection. Histological study disclosed a massive infiltration of mononuclear cells in the liver, mimicking intrahepatic hypersensitivity. Neither enterotoxigenic nor enteroinvasive Escherichia coli induced such a lesion. However, the same histopathological change was induced by injecting the hepatotoxic factor of hepatotoxigenic C. jejuni intravenously on two occasions separated by 14 days. Neither a single injection of an increased dose of the hepatotoxic factor nor two injections, the second of which was heat-inactivated, induced this change. Pre-treatment with rabbit antibody to the hepatotoxic factor inhibited the development of the hepatic lesion. These results suggest that C. jejuni-induced hepatic lesions in mice may be caused, at least in part, by the active moiety of the hepatotoxic factor. The possible mechanisms by which the toxic factor induces hepatitis as a consequence of hypersensitivity are discussed in relation to Guillain-Barré syndrome and Reiter's syndrome associated with C. jejuni enteritis.

Animals↗
PubMed1992

Mechanism of the protective immunity against murine typhoid: persistence of Salmonella L forms in the liver after immunization with live-cell vaccines.

Live-cell vaccines of Salmonella typhimurium, either a sub-lethal dose of a wild-type (strain LT2) or a high dose of its two-heptose Rd1 mutant (strain SL1004), induced acquired resistance to murine typhoid, which remained 180 days after immunization. Growth of S. typhimurium as a bacillary form ceased between days 30 and 60 of immunization, but L forms of this bacterium colonized the liver (the mean number of L forms in the liver: 600 L-forming units) even at 180 days post-immunization. In contrast, a high inoculum of either a Ra mutant (strain TV148) of strain LT2 or S. schottmülleri 8006 sharing the same O antigenic components with those of S. typhimurium induced only a short-lived protection in proportion to the number of L forms in the liver, and the protective immunity was lost before day 180. However, there was no significant difference in the salmonella-specific T-cell responses among groups of immunized mice on day 180 of immunization. A lethal infection with strain LT2 in mice which had been immunized 75 days previously with living cells of strain SL1004 resulted in a rapid clearance of the challenge inoculum, together with a rapid elevation of anti-S. typhimurium antibody responses. Thus, the present data suggest that the long-lived immunity conferred upon live S. typhimurium vaccines is attributable to the colonization of this bacterium in the liver as L forms and the ability to colonize the liver as L forms is independent of the chain length of salmonella O-antigens.

Animals↗
PubMed1992

Substitution of non-catalytic stem and loop regions of hammerhead ribozyme with DNA counterparts only increases KM without sacrificing the catalytic step (kcat): a way to improve substrate-specificity.

In elucidating structure-function relationships and stabilizing ribozymes in vivo, several chimeric RNA/DNA ribozymes and substrates were chemically synthesized. Measurements of kinetic parameters revealed that the maximally deoxyribonucleotide-substituted ribozyme (DRDRD32) gained the highest catalytic activity reaching the kcat value of > 10 min-1, the highest value ever reported for hammerhead-type ribozymes. Since these chimeric ribozymes are more stable than the wild-type all-RNA ribozymes in vivo and they also possess higher substrate-specificity, they are considered to be better candidates for antiviral therapeutic agents.

Base Sequence↗
PubMed1992

Identification of important bases for the self-cleavage activity at two single-stranded regions of genomic HDV ribozyme.

In order to determine important bases at two single-stranded regions [SSrA (726-731 nt) and SSrB (762-766)] derived mainly from secondary structure models in genomic hepatitis delta virus (HDV) ribozyme possessing self-cleavage activity, we have constructed several point mutants at these two regions on the HDV88 molecule (683-770). Among the bases at SSrA and SSrB regions C763 was found to play an essential role during self-cleavage process since substitutions to any other bases viz. A or G or U completely abolished the activity.

Base Sequence↗
PubMed1991

Genetic relationship between the HA genes of type A influenza viruses isolated in off-seasons and later epidemic seasons.

From January 1985 to March 1989, off-season viruses of H1N1 and H3N2 subtypes of influenza A viruses were isolated on five occasions in Japan. The HA gene sequences of the influenza A(H1N1) and A(H3N2) viruses isolated in Japan from 1985-9 were analysed and the phylogenetic tree for each subtype virus was constructed to determine any genetic relationship between viruses isolated in off-seasons and the epidemic viruses of the following influenza seasons. In one instance with H1N1 viruses in 1986 and in two instances with H3N2 viruses in 1985 and 1987, the spring isolates were genetically close to some of the winter isolates and were considered to be the parental viruses of the following influenza seasons. However, even in these cases, influenza viruses of the same subtype with different lineages co-circulated in Japan.

Amino Acid Sequence↗
PubMed1991

Virulence of transparent and opaque colony types of Neisseria gonorrhoeae for the genital tract of mice.

The virulence of transparent (Tr) and opaque (Op) colony types of Neisseria gonorrhoeae in the genital tract of female mice was evaluated at two stages of oestrous. Isogenic pairs of Tr and Op variants were isolated from N. gonorrhoeae strain 57-120. Both variants exhibited a T2 morphology, but only the Op variant possessed protein II (P.II) in outer-membrane fractions. When administered by intravaginal inoculation Op gonococci were highly infective only for mice in late pro-oestrous, whereas Tr gonococci were virulent for mice at both late pro-oestrous and dioestrous. Gonococci recovered from the uterus were of both Tr and Op phenotypes in equal proportions when mice were infected at dioestrous with Tr cells. In contrast, greater than 90% of recovered colonies were of Op phenotype when mice were infected at late pro-oestrous with either Op or Tr cells. These results indicate that the virulence of gonococci for the genital tract of female mice differs from that for the chicken embryo. Furthermore, gonococcal survival in the female genital tract might be attributable to phase variation from Tr to Op phenotypes.

Animals↗
PubMed1991

Biological functions of the water-insoluble fraction of mouse seminal vesicle fluid. I. Suppression of the blastogenic response of lymphocytes.

The effects of the water-insoluble fraction of mouse seminal vesicle fluid (WIF-SVF) on lymphocytes was investigated to clarify its role in reproductive immunity. WIF-SVF inhibited the blastogenic response of T-cells to concanavalin-A (Con-A), but it did not inhibit the blastogenic response of B-cells to lipopolysaccharide (LPS). Pretreatment of splenocytes with WIF-SVF did not suppress the blastogenic response of splenocytes to Con-A when treated cells were washed prior to culture. WIF-SVF did not inhibit the proliferation of Con-A activated splenocytes, the response of listeria-immune splenocytes to listerial antigen, or the proliferation of IL 2-dependent HT-2 cells, or the growth of tumour cells (Yac 1 cells, Ehrlich ascites carcinoma cells, EL-4 cells). A listerial antigen-specific immune response was not induced after mice were immunized with both listerial antigen and WIF-SVF. WIF-SVF is mainly composed of protein and its suppressive activity was enhanced by heating at 100 degrees C. These results suggest that WIF-SVF inhibits the responsiveness of T-cells to antigens or mitogens non-specifically at the initial stage.

Animals↗
PubMed1991

Suppressive effect of a mouse testicular extract on lymphocyte activation.

The effect of mouse testicular extract (TE) on lymphocyte activation was investigated. TE, in the dose range 75-600 micrograms ml-1, suppressed significantly the blastogenic response of splenocytes to concanavalin A (Con-A), pokeweed mitogen (PWM), phytohaemagglutinin (PHA) and lipopolysaccharide (LPS). TE also suppressed the blastogenic response of B-cells to LPS and of T-cells to PHA in a dose-dependent manner as well as suppressing the mixed lymphocyte reaction (MLR). Pretreatment of splenocytes with TE did not however, completely suppress their blastogenic response to Con-A, when the treated cells were washed prior to culturing. Furthermore, TE did not inhibit the on-going blastogenesis of splenocytes that had been activated already with Con-A for 48 h. Splenocytes obtained from TE-treated mice remained capable of responding to Con-A stimulation, whereas they did not respond to listerial antigens when mice were immunized with Listeria monocytogenes together with TE. The effects of TE were enhanced significantly by heating to 100 degrees C, but were resistant to pronase, RNase and DNase. These results suggest that TE affects non-specifically the stage of lymphocyte sensitization to antigens or mitogens.

Animals↗
PubMed1991

Requirement of the conformational stability of a Salmonella ribosomal vaccine for its mouse protection.

The 43-kDa non-O antigenic component isolated from the crude ribosomal fraction of Salmonella typhimurium [9] was further purified by affinity chromatography (43-kDa protein: 43-kDp). Immunization with 43-kDp did not induce complete mouse protection in CF1 mice to 500 LD50 of S. typhimurium, although it elicited a substantial IgG antibody response. The 43-kDp exhibited the mitogenicity to splenocytes (CF1 and C3H/HeJ) and B cell-rich populations (CF1). Complexing 43-kDp with the compact ribosomes of Streptococcus pyogenes by formaldehyde (complex vaccine: CV) elicited both IgM and IgG antibodies to 43-kDp. CV induced a boosting effect to enhance IgG antibody response. Moreover, CV generated delayed-type hypersensitivity to salmonella antigens and also conferred complete protection against 500 LD50 challenge of S. typhimurium to CF1 mice. These abilities of CV were reduced or impaired by RNase digestion. CV was able to induce partial or complete protection in inbred mouse strains (C3H/HeN, C3H/HeJ, DBA/2 and A/J). These data, in addition to other reports, suggest that conformational stability between ribosomes and contaminating substances such as 43-kDp or O-antigens might be required for the overall effects of the ribosomal vaccine.

Animals↗
PubMed1990

Hormonal regulation of soluble immune response suppressor (SIRS): a possible role of SIRS in the maintenance of pregnancy.

This study was conducted to investigate the effects of sex hormones upon the nature of soluble immune response suppressor (SIRS) produced by concanavalin A-stimulated Lyt-2+ T cells. Conventional SIRS affected IgM PFC only. However, SIRS made with progesterone (20-400 ng/ml or Prog-SIRS) suppressed IgM PFC, one-way MLR, and generation CTL; and SIRS made with estrogen (0.2-50 ng/ml or Est-SIRS) enhanced these responses. The factor(s) (MW 40,000-55,000) to stimulate macrophages to produce the second soluble factor (M phi-SF) was isolated from all preparations by gel filtration. Furthermore, Est-SIRS contained a factor(s) (MW 10,000-30,000) to enhance IgM PFC, MLR, and mitogen-induced blastogenesis of both T and B cells; and Prog-SIRS possessed the suppressive factor(s) to IgM PFC, MLR, and mitogen-induced T-cell proliferation. These activities were not impaired by 2-mercaptoethanol. Moreover, the suppressive activity of Prog-SIRS was completely absorbed by T cells only, but the enhancing activity of Est-SIRS was not completely absorbed by a single-cell population. These data suggest that progesterone can contribute to the suppression of allograft rejection through soluble factors, and estrogen can enhance host responses which may be affected by several soluble factors during pregnancy.

Animals↗
PubMed1990

Hepatotoxic activity of Campylobacter jejuni.

Hepatotoxic factor(s) were isolated from whole-cell lysates of Campylobacter jejuni GIFU 8734 and purified by chromatography. A single intravenous injection of 10 micrograms of this factor reproducibly produced hepatitis in mice, as determined by histology and liver function tests. The hepatic lesions were very similar to those evoked by C. jejuni infection. Tissue-culture studies with mouse hepatocytes demonstrated that low concentrations of the factor caused release of hepatic enzymes into the medium without appreciable cytolysis. High concentrations of the factor induced cytolysis. These effects were neutralised by antiserum to the factor, but not by antisera to the lipopolysaccharide of C. jejuni or to the heat-labile enterotoxin of Escherichia coli. Among 20 clinical isolates of C. jejuni, only four evoked hepatitis in mice and produced the hepatotoxic factor.

Albumins↗
PubMed1990

Enhanced interleukin production after long-term administration of erythromycin stearate.

The effects of erythromycin stearate (10 mg/kg/day) were studied on productions of interleukin (IL)-1 and -2 in mice after a long-term treatment. A 28-day treatment resulted in higher levels of IL-1 production by macrophages and of IL-2 production by splenocytes, while a 7-day treatment did not increase them. T-cell growth factor activity of IL-2 preparation prepared on day 28 of treatment as determined by HT-2 cell proliferation was reduced by about 40% in the presence of anti-murine IL-4 monoclonal antibodies, while control IL-2 activity was not reduced. Furthermore, a 28-day treatment with erythromycin stearate increased concanavalin A-induced blastogenesis of splenocytes significantly. These results suggest that long-term treatment with erythromycin stearate can stimulate host defense by increasing interleukin production.

Animals↗
PubMed1990

Biological functions of mouse seminal vesicle fluid. I. Suppression of blastogenic responses of lymphocytes.

The effect of mouse seminal vesicle fluid (SVF) on blastogenic response of splenocytes to mitogens was investigated. SVF significantly suppressed blastogenic response of splenocytes to concanavalin A and phytohemagglutinin in a dose-dependent manner, but blastogenic response to lipopolysaccharide was suppressed only at low, although significant, levels, even at high concentrations of SVF. Extensive dialysis did not reduce the capacity of SVF to inhibit blastogenesis of splenocytes. For elucidation of the mechanisms of suppression of blastogenic response, interleukin-2 (IL-2)-dependent cells were cultured in the presence of IL-2 and various concentrations of SVF. The presence of SVF did not inhibit the proliferative response of IL-2-dependent cells to IL-2. These results suggest that the suppression of blastogenic response of T lymphocytes to mitogens in seminal plasma is caused by an undialyzable component (or components) derived from seminal vesicle and is attributable to the alteration of receptors for mitogens or of IL-2 receptors that are expressed on stimulation by mitogens.

Animals↗
PubMed1990

Biological functions of mouse seminal vesicle fluid. II. Role of water-soluble fraction of seminal vesicle fluid as a nonspecific immunomodulator.

The suppressive mechanisms of T cells induced by water-soluble fraction of mouse seminal vesicle fluid (WSF-SVF) were investigated to clarify its immunological roles in the reproductive immunity. WSF-SVF inhibited the blastogenic responses to concanavalin A (Con A) or phytohemagglutinin (PHA) of T cells. Pretreatment of splenocytes with WSF-SVF did not suppress the blastogenesis of splenocytes to Con A when treated cells were washed before cultures. WSF-SVF did not inhibit the proliferation of Con A-activated splenocytes, that of listeria-immune splenocytes to listeral antigen and growth of tumor cells (Yac 1 cells, Ehrlich ascites carcinoma cells, EL 4 cells). Listerial antigen-specific immune response was not observed when mice were immunized with both listerial antigen and WSF-SVF, whereas it was observed when mice were immunized with only listerial antigen. WSF-SVF also significantly inhibited allogenic MLR. WSF-SVF did not adsorb Con A, and its suppressive activity was rather enhanced by heating at 56 degrees C for 30 min. These results suggest that WSF-SVF inhibits the stage of sensitization of T cells with antigen or stimulant, such as mitogen nonspecifically, without adsorption to antigen or mitogen, and its substance is stable.

Animals↗
PubMed1990

Nonspecific stimulation of host defense by Corynebacterium kutscheri. II. Isolation of the active moiety.

The isolation and determination of biological activities of the active component of Corynebacterium kutscheri were attempted in the present investigation. The antitumor effect was confined to the subcellular particle fraction of this bacterium and was associated with a molecule of glycoprotein nature (40,000-38,000 Daltons) isolated from this fraction by affinity chromatography with concanavalin A-Sepharose 4B. This substance exerted mitogenic activity on C3H/HeJ splenocytes and T cells, stimulatory activity on macrophages, and further exhibited antitumor effect on P388 leukemia in CDF1 mice. The Winn assay disclosed that the antitumor effect induced by this substance was dependent on L3T4+ T cells. Furthermore, both the mitogenic and antitumor activity of this moiety were resistant to heating at 100 degrees C for 30 min or RNase digestion, but sensitive to trypsin digestion, or low or high pH. These results indicate that the antitumor effect of C. kutscheri is attributable to the heat-stable glycoprotein moiety which can directly stimulate T cells and macrophages.

Animals↗
PubMed1989

Alterations of host resistance to mouse typhoid infection by sex hormones.

The effect on mouse typhoid infection of a 3-day treatment of female virgin mice with 1 mg/day of female sex hormones (estrogen or progesterone), maintaining the same hormonal levels observed in pregnant mice for 30 days, was investigated in order to clarify the mechanisms of altered resistance during pregnancy. Estrogen-exposed mice were more susceptible to the intraperitoneal challenge with Salmonella typhimurium as compared with the vehicle control mice, while progesterone treatment increased the survival times of mice. Estrogen exposure increased the number of peritoneal cells after treatment, but the inflammatory cellular response after infection was significantly suppressed. Although the estrogen-treated and vehicle control mice had the same degrees of peritoneal cellular responses after infection, the death rates in the estrogen-treated mice were higher than those in the vehicle control mice against challenge with 1 LD50 of S. typhimurium. On the other hand, progesterone treatment resulted in the marked influx of peritoneal cells after treatment was terminated, and also it induced a significant increase in the number of peritoneal cells after infection. Although survival times in the progesterone group were higher than those in other groups, all progesterone-treated mice died after a challenge with 1,000 LD50 of S. typhimurium. These results suggest that progesterone enhances nonspecific resistance by increasing the influx of peritoneal cells after infection, while estrogen affects the acute inflammatory responses.

Animals↗
PubMed1989

Effects of mouse testicular extract on immunocompetent cells.

We investigated mouse testicular extract (TE) to clarify its biological functions in reproductive immunity. TE, at concentrations of 50-300 micrograms/ml, enhanced macrophage activities of spreading, glucose consumption, and cytostasis against a susceptible tumor cell line. On the other hand, TE inhibited concanavalin A (Con A)-induced T-cell blastogenesis in the dose range of 10-600 micrograms/ml. To elucidate the origin of TE, W/Wv mice, which genetically lack germ cells, were used. TE obtained from W/Wv mice enhanced the spreadability of macrophages and inhibited Con A-induced blastogenesis of T cells. The enhancement of macrophage spreading was only achieved by the interstitial fluid (IF), while the suppression of Con A-induced T-cell responses was detected in seminiferous tubule fluid (STF) as well as in IF. TE did not affect listerial antigen-specific responses of lymphocytes in vitro. These results suggest that TE has the capacity to regulate the biological responses associated with reproduction.

Adjuvants, Immunologic↗