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Biomedical subjects

N Ishida

Publications and source records attributed to N Ishida.

At least 361 records · Page 20Linked to original sources
PubMed1985

Clinical and pathogenic studies on aged polyuria in the IVCS strain of mouse.

As aged polyuria is often observed in the IVCS strain of mouse, biochemical and histological studies were undertaken in order to clarify its etiology. Polyuria was observed at 7-8 months of age, and significant increases in water intake and urine volume were noted at 10-11 months of age. IVCS strain mice over one year old showed water intakes and urine volumes about five to six times greater than those in DDI strain mice. The osmolarity of urine excreted from polyuric mice was low compared with DDI strain mice, and elevations of sodium and potassium excretion were observed at an early stage of polyuria. At a more advanced stage of the disease, proteins of low molecular weight were excreted in most animals. Furthermore, depression of kidney response to ADH was recognized soon after onset of polyuria compared with normal IVCS strain mice. Thus, polyuria observed in IVCS strain mice may result from a functional defect of the renal tubules. In addition, significant deposition of amorphous substances, especially in the liver, kidney and spleen, occurred almost in parallel with polyuria. From these findings, it is obvious that mice of the IVCS strain exhibit characteristic polyuria and storage disease as they age.

Aging↗
PubMed1985

Inhibition of sterol and DNA syntheses in phytohemagglutinin-stimulated human lymphocytes by 7 alpha-hydroxycholesterol.

Sterol and DNA syntheses were induced in human peripheral blood lymphocytes stimulated with phytohemagglutinin (PHA). DNA synthesis in the PHA-stimulated lymphocytes was suppressed by 7 alpha-hydroxycholesterol (7 alpha-HC). The maximum suppression of DNA synthesis was observed when 7 alpha-HC was added in the culture within 6 hr of PHA stimulation to the lymphocytes. However, as the concentration of fetal bovine serum (FBS) in the culture medium was increased, the inhibitory effect of 7 alpha-HC on the syntheses of sterol and DNA were decreased. Furthermore, low and high density lipoproteins completely reversed the inhibition of DNA synthesis by 7 alpha-HC. These results suggest that cholesterol is an essential requirement of lymphocyte blastogenesis regardless of whether the source of the sterol is exogenous or endogenous.

Cholesterol↗
PubMed1985

Nucleosidediphosphate-kinase induction by human recombinant IL-2 in mouse NK cells.

The ability of human recombinant IL-2 to induce NDP-kinase in mouse NK cells has been studied. A significant increase in the amount of NDP-kinase was observed when the cells were exposed to IL-2 (100 units/ml) for 3 h at 37 degrees C. The enzyme inducting ability of human recombinant IL-2 was similar to that of native mouse IL-2 in the cells. The enzymatic characteristics [chemical requirements for the phosphoenzyme formation and molecular size of two distinct subunits (18,000 and 20,000 daltons)] of NDP-kinase from IL-2 treated cells were similar to those of the enzymes from EAT cells. The enzyme's biological role in the initiation of cell proliferation by IL-2 has been discussed.

Animals↗
PubMed1985

[Antitumor effect of human interferon-alpha A/D in mice (II). Activation of natural killer cells and suppression of metastasis].

Human recombinant interferon-alpha A/D (IFN-alpha A/D) is known to be effective on murine cells. We studied the in vivo effects of pure IFN-alpha A/D on murine splenic natural killer (NK) activity and experimentally induced pulmonary metastasis of B16-F10 melanoma. Intraperitoneal injection of IFN-alpha A/D augmented splenic NK activity, and suppressed melanoma metastasis. This suppression was abrogated by pretreatment of mice with anti-asialo GMl, but not with silica or carrageenan, showing that the effect of IFN-alpha A/D was dependent on NK cells. The suppression was strongest when IFN-alpha A/D treatment was given 12 hrs before or at the same time as tumor injection, showing that NK cells are most effective in the early phase of melanoma metastasis.

Animals↗
PubMed1985

[Antitumor effect of OK-432 (3)--mechanisms of tumor growth inhibition by OK-432 induced activated macrophages].

Spleen cells and peritoneal exudate cells obtained from BALB/c mice which had received an i.p. injection of 0.1 mg of OK-432 4 days previous to sacrifice, were examined by Winn's neutralization assay for their antitumor activity against Meth-A sarcoma cells in BALB/c mice. Both of the cell preparations clearly inhibited the growth of admixed Meth-A cells, but when these same cell populations were treated on a Sephadex G-10 column, the effector activity seen in Winn's assay disappeared. The effector cells responsible for tumor inhibition were therefore considered to be cytotoxic macrophages. However, the inhibitory effect of these cytotoxic macrophages in Winn's assay was not evident in either X ray (300 rad)-irradiated BALB/c mice or in nu/nu BALB/c mice. These results indicate that the antitumor activity of cytotoxic macrophages is associated with a sequential immune mechanism in which T cells may play an important role.

Animals↗
PubMed1985

[Antitumor effect of human recombinant interferon-alpha A/D in mice(I): Comparison between systemic and lesional treatment of meth-A sarcoma in BALB/c mice].

Human recombinant interferon-alpha A/D (IFN-alpha A/D) is known to be as active on murine cells as on human cells. We studied the antitumor effect of pure IFN-alpha A/D on Meth-A sarcoma cells in vivo. When administered systemically (intraperitoneally), IFN-alpha A/D (total dosage: 7 X 10(5) units/mouse) was only marginally but significantly (p less than 0.05) effective in reducing the growth of Meth-A sarcoma cells transplanted subcutaneously into syngeneic BALB/c mice. By lesional (intra-tumor) administration (total dosage: 5 X 10(4) to 5 X 10(5) units/mouse), however, IFN-alpha A/D strongly inhibited the growth of Meth-A sarcoma cells and even led to a complete regression of tumor growth and subsequent immunity to Meth-A sarcoma cells in the host animals when treatment was started early after transplantation and at a high dose. Indomethacin or cyclophosphamide administered intraperitoneally at a dose at which, although not directly effective against tumor growth, both were expected to stimulate the host immune system by inhibiting suppressor macrophage function or suppressor T cells, respectively, showed neither enhancing nor suppressing effect on the above mentioned strong antitumor effect of locally administered IFN-alpha A/D.

Animals↗
PubMed1985

[Antitumor effect in mice of an organic germanium compound (Ge-132) when different administration methods are used].

The antitumor effect of an organic germanium compound, carboxyethylgermanium sesquioxide (Ge-132), was examined in mice using two systems: one, the ascitic form of Ehrlich carcinoma in DDI mice, and the other, the solid form of Meth-A fibrosarcoma in BALB/c mice. In the mice with Ehrlich ascitic tumors, a remarkable prolongation in life span was observed after intraperitoneal (i.p.) or per oral (p.o.) administration of Ge-132 (300 mg/kg), but not after intravenous (i.v.) injection of the same compound. Following i.p. or p.o. administration, cytotoxic macrophages (Mø) were induced in the peritoneal cavity after 48 h. although this was not the case after i.v. injections. When the in vivo effect of these in vitro active Mø was examined after adoptive transfer to mice bearing Ehrlich ascitic tumor cells, a significant antitumor effect was noted. In the mice bearing solid Meth-A tumors, i.v. injections of Ge-132 (100 mg/kg) were found to inhibit tumor growth remarkably, although i.p. and p.o. administrations did not have the same result. This inhibitory effect of Ge-132 by i.v. administration was explained by the continued augmentation of NK activity in peripheral blood, which was followed by the induction of specific killer cells appearing in the spleen. When the mice which had recovered from Meth-A tumor growth, following i.v. injections of Ge-132, were challenged with the same tumor on day 30, all mice were able to tolerate the challenge, but not a challenge of RL male 1 tumor cells. These observations may indicate that the differing antitumor effects of Ge-132 produced when different administration methods are used can be explained by the variation in effector cells induced by such different administration routes.

Administration, Oral↗
PubMed1985

[Establishing guidlines for dealing with mild dysplasia through cytology and colposcopy (follow up study)].

230 cases of mild dysplasia, detected in examinations for cancer of the uterus, were followed up cytologically, and colposcopically for more than 2 and a maximum of 10 years, and the following results were obtained: Mild dysplasia resulted in regression in 169 cases (73.5%), persistence in 46 cases (20.0%), and progression in 15 cases (6.5%). Out of the group with progression, 10 cases (4.3%) developed into carcinoma in situ or microinvasive carcinoma. The average period required for the progression was 54.8 months. The combined use of cytology and colposcopy is useful for diagnosis and follow up of mild dysplasia. In the combined use of cytology and colposcopy, it is appropriate to evaluate the outcome (progression or regression) of mild dysplasia 2 years after detection. The transformation ratio at the time of the initial examination was in many cases higher in the progression group than in the regression group. In the progression group an increase in the transformation ratio was noted in all cases, and it appears that it is also necessary to pay attention to changes in the transformation ratio, in addition to the grading of the findings.

Adult↗
PubMed1984

Establishment of human monoclonal anti-DNA antibody producing cell lines.

We developed a useful method for the establishment of stable cell lines producing human monoclonal anti-DNA antibody by in vitro Epstein-Barr virus infection. The practical limitation for the cloning was overcome by 2 procedures. One was a microculture system using a small number of the culture. Another was enrichment of anti-DNA producing cells at an early stage and prior to the cloning. The combination of these procedures allowed ready derivation of the cell lines secreting monoclonal anti-DNA antibody. Sixteen cell lines were cloned by utilizing colony formation methods in soft agarose. About 14-32 micrograms per ml of IgM with specific antibody activity were obtained in the supernatant of the cells. The antibody reacted with double-stranded and/or single-stranded DNA. These cells have been continuously producing the specific antibody for more than 3 years. We may extend this procedure for obtaining other autoantibodies, such as anti-T cell antibodies.

Animals↗
PubMed1984

Relationships between suppressor macrophages and macrophage precursors in the spleens from tumor-bearing mice.

Suppressor macrophages (M phi) which can inhibit mitogen-induced lymphocyte proliferation appeared in the spleens of mice bearing transplanted MC-A fibrosarcoma cells. An analysis of the ontogeny of such M phi revealed additional suppressor activity directed against macrophage stem cells. Treatment of spleen cell suspensions with carbonyl iron followed by centrifugation removed suppressor M phi but did not deplete M phi-colony forming cells (M-CFC) which could be demonstrated in soft agar culture in L-cell conditioned medium (LCM). Untreated spleen cells had normal numbers of M-CFC; phagocyte-depleted mononuclear cells showed a threefold increase in M-CFC 14 days after subcutaneous inoculation of 10(6) MC-A cells per mouse. Further increases in M-CFC were also evident in similar preparations on Days 21 and 28 when the M-CFC concentration reached a maximum of eight times the normal level. The M phi which developed from the M-CFC grown in the presence of LCM were later shown to have indomethacin-sensitive suppressor activity suggesting the mediation of this phenomenon by prostaglandins. These observations suggest that locally produced phagocytic suppressor M phi from the spleens of tumor-bearing mice play important roles not only as inhibitors of lymphocyte proliferation as reported earlier, but also as regulators of monocyte-M phi production.

Animals↗
PubMed1984

Activated macrophages are responsible for the tumor-inhibitory effect in mice receiving intravenous injection of OK-432.

Mouse spleen cells, either pretreated in vitro with 100 U/ml of OK-432-induced IFN gamma for 18 h or obtained from mice 24 or 48 h after i.v. injection of OK-432(100 micrograms/mouse), were examined for their anti-tumor effect by Winn's neutralization assay against Meth-A tumor cells in BALB/c mice. Spleen cells treated in vitro or obtained in vivo 24 h after i.v. injection clearly neutralized the growth of admixed Meth-A cells. Two booster injections of 200 U of IFN gamma near the tumor site accelerated this neutralizating effect. In order to determine the effector subpopulation, inhibitory spleen cells were treated with either anti-Thy-1 monoclonal antibody plus complement, anti-asialo GM1 serum plus complement or with adherence on plastic plates followed by Sephadex G-10 column treatment. The effector cell activity in Winn assay was lost only after the removal of macrophages through plastic plate adherence and Sephadex G-10 column treatment, but not after anti-Thy-1 or anti-asialo GM1 treatment, with either in vitro- or in vivo-treated spleen-cell populations. The growth of Meth-A cells was inhibited not only by these activated macrophages in Winn's assay, but also by adoptive transfer of OK-432-induced cytotoxic macrophages intralesionally 4 days after the implantation of 1 X 10(6) Meth-A cells. Our evidence suggests that the systemic action of OK-432 can be explained by the effect of induced IFNgamma, through the activation of macrophages.

Animals↗
PubMed1984

Corneal nerve alterations in diabetes mellitus.

The morphologic status of corneal innervation was studied in rats with streptozocin-induced diabetes. Animals were killed at 1, 4, 16, and 36 weeks. Corneal innervation was studied by light and electron microscopy using nonspecific cholinesterase reaction, gold chloride impregnation, and plastic-embedded sections. Increased irregularity in the periodicity of nerve fiber beading was observed in diabetic corneas with gold impregnation. Ultrastructural evidence of irregularities in the basal lamina of Schwann cells was demonstrated in 16- and 36-week-old diabetic animals, along with occasional axonal degeneration. These alterations constitute a constellation of early pathologic manifestations in the innervation of diabetic cornea. To our knowledge, this study represents the first demonstration of neural changes in diabetic corneas as well as nerve fiber changes in an avascular tissue in diabetes.

Animals↗
PubMed1984

Three different serotypes of human rotavirus determined using an interference test with coxsackievirus B 1.

MA104 cells were used to titrate human rotavirus, and its capacity to render the cells resistant to coxsackievirus B 1 infection enabled us to determine easily the infectious titer of three prototype human rotaviruses. When rabbit antisera prepared against these prototype viruses were used for the neutralization test, the viruses could be discriminated from each other by a specific neutralization test.

Enterovirus B, Human↗
PubMed1984

Hemagglutination by human rotavirus strains.

Human rotavirus isolates, KUN , MO, and Wa strains were found to agglutinate erythrocytes of the day-old chicken and adult goose, optimally at pH 6.6. Only those fractions containing double-shelled rotavirus particles isolated by isopycnic centrifugation in cesium chloride had hemagglutinating activity. Trypsin treatment decreased the hemagglutination titer of human rotavirus strains and conversely increased their infectivity. Hemagglutination inhibition tests with antisera against type-specific antigens demonstrable by neutralization showed no type specificity.

Animals↗
PubMed1984

Further observations on the morphogenesis of human rotavirus in MA 104 cells.

Human rotavirus "KUN" strain was cultivated in a fetal rhesus monkey kidney cell line, MA 104 cells. Four types of virus particles in cells infected with KUN strain were clearly identified: nucleoid cores, single-shelled particles, double-shelled particles, and membrane band, "enveloped" particles. "Enveloped" particles were found only in the thin sections of infected cells. When first visible, the virus precursors appeared at the ribosome free membrane of rough endoplasmic reticulum (RER), increasing in size while simultaneously being coated with nucleocapsid, inner shell. Single-shelled particles were also synthesized within bundles of filaments of viroplasm in the cytoplasma. During subsequent virus maturation two types of "budding" processes were observed. Double-shelled particles arising at the RER membrane entered the cisternae of the RER through an exocytosis-like process. In contrast, the "enveloped" particles developed in the cisternae by being completely enclosed with RER membrane, and later during cytolysis released the single-shelled particles. These "enveloped" virus particles appeared to be the result of inefficient virus maturation at the last stage of outer capsid formation.

Animals↗
PubMed1984

Treatment of multiple sclerosis with anti-measles cow colostrum.

Previous virological and immunological studies have suggested that multiple sclerosis (MS) is an auto-immune disease triggered by a virus infection. In order to inhibit the growth of measles virus in the patient's jejunum, we obtained an IgA-rich cow colostrum containing anti-measles lactoglobulin resistant to proteases. This colostrum was orally administered to patients with MS to investigate its effect on the course of the disease. Measles-positive antibody colostrum was orally administered every morning to 15 patients with MS at a daily dosage of 100 ml for 30 days. Similarly, measles-negative antibody (less than 8) control colostrum was orally administered to 5 patients. As a clinical assessment, disability scores developed by the International Federation of Multiple Sclerosis Societies were used. As a result, of 7 high NT titre (512-5120) anti-measles colostrum recipients 5 patients improved and 2 remained unchanged. Among 8 low NT titre (8-32) anti-measles colostrum recipients 5 patients improved and 3 remained unchanged. However, of 5 negative NT titre (less than 8) colostrum recipients 2 patients remained unchanged and 3 worsened. No side-effects were observed in colostrum recipients. These findings suggest the efficacy of orally administered anti-measles colostrum in improving the condition of MS patients (P less than 0.05).

Adolescent↗