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Biomedical subjects

I Kawamura

Publications and source records attributed to I Kawamura.

At least 55 records · Page 3Linked to original sources
PubMed1995

Correlation between the presence of virulence-associated genes as determined by PCR and actual virulence to mice in various strains of Listeria spp.

Five chromosomal genes, prfA, plcA, hlyA, mpl and plcB, are implicated in the virulence of Listeria monocytogenes and some of these genes have been used for the identification of bacteria by polymerase chain reaction (PCR). Using 6 strains of L. monocytogenes and 3 L. innocua strains, the relationship was examined between the presence of five virulence-associated genes and actual virulence to mice in terms of 50% lethal dose (LD50), bacterial viability in the organ of infected mice and the intracellular growth in cultured macrophages. None of the five genes could be amplified by PCR in all the L. innocua strains and they were actually avirulent to mice. All L. monocytogenes strains were shown to be virulent and to have intact virulence-associated genes except for the strain ATCC15313. This particular strain was revealed to be avirulent and defective in hlyA and plcA in PCR amplification. It was suggested that PCR detection of genes prfA, mpl, or plcB may not be sufficient to detect virulent strains of L. monocytogenes. It appeared that the ability to produce listeriolysin O (LLO), which is encoded by hlyA, was critical for the expression of virulence regardless of the amount of LLO produced.

Animals↗
PubMed1995

A new aromatase inhibitor, FR901537. II. Pharmacological and antitumor effects.

The pharmacological and antitumor effects of FR901537, a new aromatase inhibitor, isolated from Bacillus sp. No. 3072, were studied. Treatment for four consecutive days with FR901537 inhibited the androstenedione-induced increase in the uterus weight in immature rats. FR901537 had no effect on the uterus, adrenal glands, ovary or pituitary weights in mature rats following 14 days of treatment. The antitumor activity of FR901537 on 7,12-dimethylbenz(a)anthracene-induced mammary tumors was studied in ovariectomized, testosterone propionate (TP)-treated rats as a postmenopausal tumor model. Ovariectomy caused the regression of the mammary tumors and the growth of tumors was remarkably stimulated following TP treatment. Further, in the rats treated with FR901537 and TP, the TP-induced tumor growth was significantly inhibited by FR901537. These results suggest that FR901537 is a promising drug in the treatment of estrogen-dependent mammary tumors in postmenopausal women.

Aminoglutethimide↗
PubMed1994

Effect of betaine on S-adenosylmethionine levels in the cerebrospinal fluid in a patient with methylenetetrahydrofolate reductase deficiency and peripheral neuropathy.

A 16-year-old Japanese girl with 5,10-methylenetetrahydrofolate reductase deficiency showed peripheral neuropathy. There were no significant responses to vitamin B6, vitamin B12 or folate, given alone or in combination. With the addition of betaine monohydrate, she has been free from gait disturbance and muscle weakness. The concentration of S-adenosylmethionine in cerebrospinal fluid, which was undetectable before receiving betaine monohydrate, increased to about the normal level 24 months after treatment with betaine monohydrate.

Adolescent↗
PubMed1994

Specific immune response to the 40-kDa outer-membrane protein of Porphyromonas gingivalis in mice.

Whether B-cell activation to Porphyromonas gingivalis in periodontal diseases is the consequence of a specific immune response or is due to non-specific polyclonal activation is still not clear. Here the immune response of mice to a purified 40-kDa recombinant protein antigen, a major outer-membrane protein specific to P. gingivalis, was investigated. Patients' sera strongly reacted to this recombinant antigen. Purified splenic T and B cells from mice immunized with 40-kDa antigen or from normal mice were reconstituted in vitro and cultured in the presence or absence of the P. gingivalis 40-kDa protein antigen and antigen-presenting cells (APCs). In vitro antibody production to this particular antigen was analysed with respect to the requirement of helper T cells and APCs by enzyme-linked immunosorbent assay. The results clearly showed that an effective secondary response required the presence of B cells, T cells and APCs. In the absence of CD4+ helper T cells, an antibody response to the 40-kDa protein was not observed. In addition, the requirement of H-2 restricted, Ia-positive APCs was evident for an adequate response to the 40-kDa protein of P. gingivalis. Thus the antibody response to the 40-kDa protein of P. gingivalis was generated in an immunologically antigen-specific manner and was not simply the result of polyclonal B-cell activation. This in vitro system could be used in the detection of antigen-specific memory B or T cells in patients with periodontal diseases.

Adult↗
PubMed1994

Ultraviolet-B irradiation alters cytokine production by immune lymphocytes in herpes simplex virus-infected mice.

Previous studies from our laboratories have shown that UV-B irradiation at the site of an intradermal infection of herpes simplex virus (HSV) resulted in a higher incidence of zosteriform lesions and suppressed cellular immune responses to HSV in mice. In order to determine whether the production of T-cell-derived cytokine (IFN-gamma, IL-2 and IL-4) by immune cells from irradiated mice is also suppressed, we examined the production of cytokines by lymph node cells and spleen cells taken from UV-B irradiated, HSV type 1 (HSV-1)-infected mice. UV-B irradiation (120 mJ/cm2) prior to HSV-1 infection was found to markedly suppress IFN-gamma production compared to that of the non-irradiated control. IL-4 production was enhanced compared to IL-2 in the UV-B irradiated mice. These results suggest that alteration(s) in the cytokine production profile may therefore be involved in the development of severe skin lesions caused by HSV infection in UV-B irradiated mice.

Animals↗
PubMed1994

Binding sites of droloxifene in the cytosol of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor cells.

The binding sites, other than the estrogen receptor (ER), of the antiestrogens droloxifene (DROL, (E)-a-[p-[2-(dimethylamino)ethoxy]-phenyl]-a'-ethyl-3-stilbenol) and tamoxifen (TAM), and estradiol-17 beta (E2) in the cytosol of 7,12-dimethylbenz[a]anthracene-induced rat mammary ER-positive tumor cells were studied using a high-performance liquid chromatography (HPLC) gel filtration assay. The cytosol was incubated with 3H-labeled drug with or without unlabeled drug, and separated by HPLC gel filtration. 3H-E2 produced two major peaks of radioactivity at fractions No. 40 and No. 70. The peak at fraction No. 70 was identified as the ER in an ER-enzyme-immuno assay. This peak was dose-dependently inhibited by unlabeled DROL or TAM, DROL being a more potent inhibitor than TAM. The peak at fraction No. 40 was also inhibited by co-incubation with unlabeled DROL or TAM. 3H-DROL or 3H-TAM provided only one peak at fraction No. 43. This peak was thought to be an antiestrogen binding site (AEBS), because it was inhibited by unlabeled antiestrogen but not by E2. The results suggest that the antiestrogens DROL and TAM have a higher affinity for the AEBS than for the ER in the absence of E2, while in the presence of E2 both have an affinity for the ER and inhibit E2 binding to the ER.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Antigen provoking gamma interferon production in response to Mycobacterium bovis BCG and functional difference in T-cell responses to this antigen between viable and killed BCG-immunized mice.

It has been shown that gamma interferon (IFN-gamma)-producing CD4+ T cells, which are generated only by immunization with viable bacteria, exert a significant role in protective immunity against mycobacteria in mice. In this study, we have tried to determine the antigen recognized by the T cells in search of a possible protective antigen. T cells from viable Mycobacterium bovis BCG-immunized mice were stimulated with several antigens, and IFN-gamma production was measured. Purified protein derivative and viable and killed BCG lysates caused significant IFN-gamma production, and almost the same level of IFN-gamma activity was detected in both groups stimulated with viable and killed BCG lysates. However, heat shock protein (HSP) 65 and HSP 70 were not a major antigen for IFN-gamma production. The antigen provoking IFN-gamma production is localized mainly in the membrane fraction of BCG cells, and the approximate molecular size was 18 kDa. On the other hand, T cells from killed BCG-immunized mice never responded to this antigen for IFN-gamma production, whereas they could mount a delayed-type hypersensitivity response. These results showed that the antigen provoking IFN-gamma production was present in killed as well as viable BCG. In addition to the antigen presentation by antigen-presenting cells, some kinds of differentiation factor (such as monokines) that are produced only by stimulation with viable cells seemed to be necessary for the development of IFN-gamma-producing T cells.

Animals↗
PubMed1994

Cytokine gene expression in mice at an early stage of infection with various strains of Listeria spp. differing in virulence.

By using reverse transcription-PCR, cytokine gene expression was examined in mice 24 h after infection with various strains of Listeria spp. differing in virulence as determined by in vivo growth and 50% lethal dose values. All the virulent strains of Listeria monocytogenes induced the expression of mRNAs specific for interleukin-1 alpha (IL-1 alpha), gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) in the spleen of mice, while an L. monocytogenes strain incapable of producing listeriolysin O and strains of Listeria innocua induced the expression of TNF-alpha mRNA only. The levels of expression of IL-1 alpha and IFN-gamma mRNAs were proportional to the levels of listeriolysin O produced by each strain. Those strains which induced the expression of IFN-gamma were capable of generating protective immunity in the infected host, suggesting that the virulence-related induction of some cytokine at the initial stage of infection plays a role in the induction of acquired cellular resistance to L. monocytogenes.

Animals↗
PubMed1994

FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice.

The antitumor activities of FR901228, (E)-(1S,4S,10S,21R)-7-[(Z)- ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23- tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,19,22-pentanone, isolated from Chromobacterium violaceum No. 968, were studied in animals. FR901228 (ip) prolonged the life of mice bearing such murine ascitic tumors as P388 and L1210 leukemias and B16 melanoma, and inhibited (iv) the growth of murine solid tumors (Colon 38 carcinoma, M5076 reticulum cell sarcoma and Meth A fibrosarcoma) and human solid tumors (Lu-65 and LC-6 lung carcinomas, and SC-6 stomach adenocarcinoma) implanted in normal and nude mice, respectively. Its antitumor activity was especially potent against murine Meth A fibrosarcoma and human SC-6 stomach adenocarcinoma which were refractory to mitomycin C or cisplatin. FR901228 also was more effective against mitomycin C-, cyclophosphamide-, vincristine- and 5-fluorouracil-resistant P388 leukemias than against non-resistant P388 in mice. These results suggest that FR901228 will be a new type of drug for the treatment of cancer.

Animals↗
PubMed1993

Membrane damage and interleukin-1 production in murine macrophages exposed to listeriolysin O.

To obtain some insight into the interaction between listeriolysin O (LLO) and the macrophage membrane, we examined the effect of purified Listeria monocytogenes hemolysin on the viability and functions of mouse peritoneal exudate macrophages. The study showed that purified LLO impaired a variety of functions of the macrophages. First, it suppressed the luminol-dependent chemiluminescence response of macrophages. Second, it suppressed the phagocytic ingestion of opsonized sheep erythrocytes and latex beads. Third, exposure of macrophages to LLO resulted in an increase in dead cells, as determined by the trypan blue dye exclusion method. An interesting observation of this study is that the LLO-induced production of interleukin-1 from macrophages could not be blocked by preincubation with cholesterol, while the membrane-damaging ability could be blocked by cholesterol. The dissociation of the blocking effects of cholesterol suggests that the interleukin-1-inducing ability of LLO may be distinct from its membrane-damaging ability.

Animals↗
PubMed1993

The estrogenic and antiestrogenic activities of droloxifene in human breast cancers.

The effects of a new antiestrogen, droloxifene (DROL, (E)-alpha-[p-[2-(dimethylamino)ethoxy]-phenyl]-alpha'-ethyl-3- stilbenol), on human breast cancer cells in vitro and in vivo were studied. Since phenol red has a binding affinity to the estrogen receptor (ER), we studied the activities of drugs in medium with or without this indicator. Estradiol-17 beta (E2) stimulated the growth of ER-positive breast cancer cells, MCF-7, ZR-75-1 and T-47D, in medium without phenol red, but not in medium containing this indicator. In medium without phenol red, DROL had no marked effects on the growth of MCF-7 and ZR-75-1, but slightly stimulated the growth of T-47D. Tamoxifen (TAM) stimulated the growth of these 3 cells. DROL dose-dependently inhibited the E2-induced stimulation of growth of these cells in medium without phenol red, but TAM inhibited the growth only at high concentrations. The growth of ER-negative breast cancer cells, MDA-MB-231, was not influenced by E2, DROL or TAM. DROL was more effective than TAM against ER-positive Br-10 breast carcinoma in nude mice, but neither drug had effects on ER-negative MX-1 breast carcinoma. These results suggest that DROL shows an antitumor effect on ER-positive breast cancers, being less estrogenic and more antiestrogenic than TAM.

Animals↗
PubMed1993

Complications of Vertical Banded Gastroplasty and its Modified Operative Mode, K-Gastroplasty: a preliminary report.

Based on the experiences in performing vertical banded gastroplasty (VBG) for 8 years, its results were analyzed and particularly its operative complications were examined. As a result, its weight-reducing effect and safety were favorable, but serious complications, although few, were observed. These major complications were the loss of gastric reduction effect due to staple-line dehiscence, gastric band exposure, reflux esophagitis, channel narrowing, pouch ulcer, etc. As a preventive measure against these complications, to supplement the defects of VBG without losing its characteristics, K-gastroplasty was devised and performed; its operative mode is discussed.

Journal Article↗
PubMed1992

IFN-gamma-producing ability as a possible marker for the protective T cells against Mycobacterium bovis BCG in mice.

We searched for a functional marker with which T cells mediating acquired cellular resistance (ACR) can be discriminated from those mediating delayed-type hypersensitivity (DTH) in mice immunized with Mycobacterium bovis BCG. Four wk after injection of the mice with 10(5) viable BCG (vBCG) cells emulsified in IFA, a passive transfer experiment revealed that T cells mediating DTH as well as ACR, which we designated TACR, were generated in the spleen. In contrast, T cells mediating only DTH (TDTH) were generated by immunization with 10(7) killed BCG cells along with IFA. The transferring ability of both TACR and TDTH was substantially reduced by treatment with anti-Thy-1.2 or anti-CD4 mAb plus complement, whereas anti-CD8 treatment had no effect. To determine the functional differences between TACR and TDTH, we assessed IL-2 and IFN-gamma production from TACR and TDTH after stimulation with PPD in vitro. Similar levels of enhanced IL-2 activity were detected in the culture supernatants of both groups of T cells. However, augmented production of IFN-gamma was observed only in TACR. This finding was confirmed by Northern blot analysis for detection of IFN-gamma-specific mRNA. In addition, a significant increase in the number of IFN-gamma-producing cells was observed only in T cells from mice immunized with vBCG. The production of IFN-gamma was also totally abolished by treatment with anti-Thy-1.2 and anti-CD4 mAb plus complement in vitro, whereas anti-CD8 mAb treatment had no effect. These results suggest that CD4+ protective T cells generated by immunization with vBCG are characterized by the ability to produce IFN-gamma after stimulation with specific Ag.

Animals↗
PubMed1992

Induction of macrophage interleukin-1 production by Listeria monocytogenes hemolysin.

Listeriolysin O produced by a hemolytic strain of Listeria monocytogenes was purified from the ammonium sulfate precipitate of a culture supernatant through the steps of ion-exchange chromatography and gel filtration. The purified hemolysin finally gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular weight of 58,000. When peritoneal exudate macrophages were stimulated with purified hemolysin, we found a high level of IL-1 activity as determined by thymocyte costimulator assay in the culture supernatant. Cell-associated and intracellular IL-1 activity was also detected. The activity in the supernatant or membrane was blocked by polyclonal antibody to murine IL-1 alpha. Moreover, IL-1-specific mRNA expression could be detected in the macrophages stimulated with listeriolysin O by Northern blot analysis. Possible contamination by LPS of the listeriolysin O preparation did not seem to contribute to the induction of macrophage IL-1 production.

Animals↗
PubMed1992

A Clinical Study of Protein Sparing Modified Fast (PSMF) Administered Preoperatively to Morbidly Obese Patients: comparison of PSMF with natural food products to originally prepared PSMF.

Morbidly obese patients are generally in a malnutritional state with an extremely high operative risk. In order to reduce the operative risk, surgeons should make every effort before the operation. A protein sparing modified fast (PSMF) may exhibit its high effectiveness when taken at least for 2 weeks preoperatively. In this study, PSMF prescribed with natural food products was compared with prepared PSMF having an ideal composition from the clinical standpoint. Though it is natural for patients to favor the former, the latter proved to have a superior effect in clinical practice. By performing a PSMF for 2 weeks preoperatively, however, even the PSMF with natural food products seemed to fulfill its purpose sufficiently.

Journal Article↗