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Biomedical subjects

N Ishida

Publications and source records attributed to N Ishida.

At least 343 records · Page 19Linked to original sources
PubMed1986

Antitumor effect of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha,alpha-trehalose (SS554), in mice.

The antitumor effect on Meth-A fibrosarcoma in BALB/c mice of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha,alpha-trehalose (designated as SS554), was examined. Only intratumoral injection had a curative effect; subcutaneous, per oral, or intravenous routes had no such effect. The co-presence of an oily vehicle has been shown to be necessary for antitumor activity of a natural cord factor. When SS554 was examined in suspensions of sesame oil, squalane, squalene or sesame oil and water emulsion, a 60% cure rate was achieved. However, no such effect was obtained with a suspension in Tween-PBS or a solution. It should also be noted that sequential but independent administrations of SS554 and oil were found to be as effective as the simultaneous administration of oil and SS554 in emulsion form. In the case of the emulsion, the amount of sesame oil necessary was over 10%, or 0.01 ml in absolute terms. Cures were obtained in a dose-dependent manner by injection of SS554 in amounts in excess of 1 mg. The effect of the time of administration was also examined; the best result was obtained when intratumoral injection was done on day 3 after tumor implantation. Mice cured by SS554 exhibited growth inhibition and rejection of rechallenged Meth-A cells. However, this immunity was specific; it did not extend to a rechallenge with RLmale-1 leukemia cells.

Animals↗
PubMed1986

Antimetastatic effect of biological response modifiers in the "double grafted tumor system".

The antimetastatic effect of biological response modifiers (BRM) in a new experimental mouse model was studied. Intratumoral administration of BRMs (PSK, OK-432, interferon alpha A/D) strongly inhibited the growth of Meth-A solid tumors in male BALB/c mice and led to a complete regression of tumors and resistance to reinoculated tumors. Subsequently, the antimetastatic effect of BRMs was examined in the "double grafted tumor system," in which mice first received simultaneous intradermal inoculations of Meth-A in the right (10(6) cells) and left (2 X 10(5) cells) flanks and were then injected with BRMs in the right tumor on day 3. PSK and interferon (IFN) significantly inhibited the growth of the left (non-treated) tumor. This finding suggests that intratumoral BRM immunotherapy in one region has an effect on tumor growth in another region. Immunized spleen cells were taken from mice which had been cured by the intratumoral administration of BRMs and had rejected reinoculated tumors. One hour after intravenous injection of cyclophosphamide (2 mg/mouse), immunized spleen cells (2 X 10(7) cells/mouse) were injected into the Meth-A tumor on day 3. Adoptive transfers of PSK and IFN immunized spleen cells caused the complete regression of Meth-A tumors. These results suggest that the intratumoral administration of BRMs might induce cytotoxic cells in the left non-treated tumor of the "double grafted tumor system" and bring about the regression of metastatic tumors.

Adjuvants, Immunologic↗
PubMed1986

[Antitumor effect of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha, alpha-trehalose (SS 554) in mice].

The antitumor effect of a synthetic cord factor (6, 6'-Di-O-decanoyl-alpha, alpha-trehalose) (SS 554) on the growth of Meth-A fibrosarcoma in BALB/c mice was examined. With regard to administration routes, only intratumoral (i.t.) injection showed a curative effect; subcutaneous (s.c.), per oral (p.o.) or intravenous (i.v.) routes has no such effect. To show the antitumor effect of known natural and synthetic cord factors, the co-presence of oily vehicles has been shown to be necessary. Accordingly, compound SS 554 examined in suspensions of sesame oil, squalane (SQA), squalene (SQE) or sesame oil and water emulsion had a curative effect with a 60% survival rate. However, no such effect was obtained with a suspension in PBS or in HCO-60 solution. In this regard, it should be noted that sequential but independent administration of SS 554 and oil was found to be equally as effective as simultaneous administration of oil with SS 554. Thus the effect of the oil should be reconsidered through an examination of the sequential appearance of effector cells. In the case of sesame oil, the amount of oil necessary was over 10%, or 0.01 mg absolutely. When the dose effect of SS 554 was examined in the presence of 10% sesame oil, doses over 1 mg exhibited a dose dependent curative effect. In tumor-bearing mice, the effect of the time of administration was also examined; the best result was obtained when intratumor injection was performed on day 3 after tumor implantation. Mice that recovered after SS 554 treatment exhibited growth inhibition and rejection of rechallenged Meth-A cells. However, this immunity was specific as it did not extend to a rechallenge with RL male-1 leukemia cells.

Animals↗
PubMed1986

Role of natural killer cells in intraocular melanoma metastasis.

The authors studied the role of natural killer (NK) cells in spontaneous metastasis of murine intraocular melanoma by transplanting murine B16 melanoma cells into the anterior chamber of the eye in syngeneic C57BL/6 mice and determining the number of metastatic lung tumor colonies after 40 days. Depletion of NK activity by anti-asialo GM1 serum dramatically enhanced metastasis and augmentation of NK activity by interferon inhibited it. The strong correlation between host NK activity and intraocular melanoma metastasis indicated that NK cells have an important role in spontaneous metastasis of intraocular melanoma.

Animals↗
PubMed1985

Molecular cloning and structure of the human interleukin 2 receptor gene.

We have cloned the IL-2 receptor gene from human genomic DNA libraries using IL-2 receptor cDNA as probe. The genomic DNA segments that hybridized with cDNA were subcloned in M13 phages and their sequences were determined. The nucleotide sequences showed that the IL-2 receptor gene was encoded by eight exons and that the coding region sequences agreed completely with that of the IL-2 receptor cDNA cloned from a cell line derived from adult T cell leukemia (ATL), in which IL-2 receptors are expressed abnormally. The nucleotide sequence of the 5'-flanking region had a putative promotor region, which had some homology with the human IL-2 gene. Transcription initiation sites were clustered about 25 bp 3' to the TATA box as assessed by primer extension analysis. These sites for normal and ATL T cells were the same. Exons 2 and 4 encoding the extracytoplasmic portion had significant homology, suggesting that the two exons are derived by duplication of an ancestral exon. Exon 2 contained six cysteine residues, four of which are conserved at the corresponding positions in exon 4.

Amino Acid Sequence↗
PubMed1985

Rat lymphoid cell lines producing human T cell leukemia virus. II. Constitutive expression of rat interleukin 2 receptor.

Three rat lymphoid cell lines (TARS-1, TARL-2, and TART-1) (12) transformed by human T cell leukemia/lymphoma virus I (HTLV-I) had rearrangement of the beta chain gene of the T cell antigen receptor, and had integrated proviral DNA from HTLV-I in their genomes. As is the case with adult T cell leukemia (ATL)-derived human T cell lines transformed by HTLV-I, these rat cell lines unequivocally expressed interleukin 2 (IL-2) receptor, as determined by radiolabeled IL-2 binding. By Scatchard plot analysis, one of the cell lines, TART-1, proved to have high affinity receptors (Ka = 1.3 X 10(11)/M and 8.8 X 10(9)/M). Rat IL-2 receptor, not human IL-2 receptor, was expressed on HTLV+ rat cell lines, as demonstrated by the fact that they expressed antigens reactive with monoclonal antibodies (ART-18) against rat IL-2 receptor, but not with anti-Tac antibodies. The collective evidence indicates that the endogenous IL-2 receptor gene is activated in human and rat lymphoid cell lines with HTLV-I production. The mechanism of abnormal IL-2 receptor expression in HTLV infection is discussed.

Animals↗
PubMed1985

Nucleotide sequence of mouse IL-2 receptor cDNA and its comparison with the human IL-2 receptor sequence.

We have cloned cDNA encoding the mouse interleukin-2 (IL-2) receptor from a murine T cell line, CTLL using human IL-2 receptor cDNA as probe. COS 7 cells transfected with the cDNA expressed the antigen recognized by the monoclonal antibody against the murine IL-2 receptor. The cDNA identified 4 species of mRNA (4.5, 3.5, 2.2 and 1.5 kb) of the mouse IL-2 receptor in CTLL cells. Difference in the length of mRNA seems to be ascribed to the variable length of the 3' untranslated sequence. Total nucleotide sequence (approximately 1400 bp) of this cDNA was determined and compared with the human receptor. The nucleotide and amino acid sequences of the IL-2 receptor are 70% and 60%, respectively, homologous in average between the two species. The comparison has revealed several conserved regions localized to particular exons such as transmembrane and cytoplasmic portions, suggesting that these regions are important for receptor function and its regulation.

Amino Acid Sequence↗
PubMed1985

Two modes of human rotavirus entry into MA 104 cells.

Entry of the KUN strain of human rotavirus into MA 104 cells was studied by electron microscopy. Virus particles attached to the cell membrane appeared to be almost exclusively double-shelled virions. These attached virions followed two distinct pathways into the cytoplasm depending on pretreatment with trypsin. Using infectious rotavirus which had been pretreated with trypsin, the viral nucleoids passed directly into the cytoplasm within 5 minutes after inoculation, through dissolution of the viral capsid and cell membrane. Using non-infectious rotavirus that had not been pretreated with trypsin, phagocytosis or pinocytosis occurred in which virions were sequestered into lysosomes 20 minutes after virus attachment to the cell membrane. After being sequestered, uncoating of the rotavirus virions within lysosomes was seen, but it did not result in release of the genome. On the basis of these observations it was concluded that when virions were pretreated with trypsin, virus replication occurred following the direct passage of viral nucleoids into the cell cytoplasm. However, mere phagocytosis of virus particles into cell lysosomes, which occurred when trypsin-untreated virus was used, does not appear to be related to rotavirus replication.

Adhesiveness↗
PubMed1985

Prevention of rotavirus infection by oral administration of cow colostrum containing antihumanrotavirus antibody.

After immunizing 8-month pregnant Holstein cows with human rotavirus, Wa strain, cow colostrum containing neutralizing antibody to human rotavirus, designated as Rota colostrum, was obtained. After randomly grouping 13 infants from a single orphanage, 6 infants received 20 ml of Rota colostrum every morning and 7 control infants received 20 ml of market milk. One month later, rotavirus associated diarrhea was observed in 6 of the 7 infants given milk and 1 out of the 6 infants given Rota colostrum. Orally administered Rota colostrum significantly protected infants from diarrhea caused by rotavirus (P less than 0.05). Two out of 5 Rota colostrum recipients who were free from diarrhea showed rises in complement fixation (CF) antibody titer after the rotavirus infection epidemic. Thus, Rota colostrum prevented the outbreak of diarrhea but did not prevent immunological responses to natural rotavirus infection. In the therapeutic trial Rota colostrum had no effect on duration of diarrhea, bowel movements or virus shedding in stool. However, there were no side-effects of Rota colostrum.

Administration, Oral↗
PubMed1985

Effect of hypertonic conditions on protein synthesis in MA104 cells infected with human rotavirus.

When a high NaCl concentration was used to decrease selectively the synthesis of cell proteins, the synthesis of most cellular polypeptides was greatly diminished relative to human rotavirus proteins. Thus, in the presence of 150 mM excess NaCl, 11 viral polypeptides were clearly identified. However, hypertonic conditions also reduced viral protein synthesis to a different extent with individual proteins. No significant changes in viral protein synthesis occurred during incubation under the hypertonic condition for up to 6 h, and infectious virus yields of MA104 cells incubated in the hypertonic medium did not differ from the yields of untreated MA104 cells. These results indicate that hypertonic conditions provide a useful tool for qualitative studies of viral protein synthesis in human rotavirus infected cells.

Cells, Cultured↗
PubMed1985

Interleukin 2 induces synthesis of polypeptides in an interleukin 2-dependent cell line by transcription and translation.

Interleukin 2 (IL 2) is a lymphocyte growth factor capable of inducing the rapid growth of antigen- or mitogen-stimulated T cells. To understand the molecular mechanisms of IL 2 action, we studied the synthesis of cellular polypeptides induced by IL 2. For a homogeneous cell population responsive to IL 2, we used a murine clone of natural killer-like cells, NK 7, which is strictly dependent on exogenous IL 2 for cell viability and growth. NK 7 cells were first kept in culture without IL 2 for 6 h and then labeled for 3 h with [14C]leucine in the presence or absence of 100 U/ml recombinant human IL 2. Analysis of the cellular polypeptides by two dimensional gel electrophoresis and autoradiography revealed that the addition of IL 2 to IL 2-starved NK 7 cells specifically increased the levels of at least ten polypeptides (designated from molecular weight as p94a, p94b, p52, p51a, p51b, p48.5, p36, p34.5, p25.5, and p23). The increases of p52, p25.5, and p23 were inhibited by 5 micrograms/ml actinomycin D, whereas the other seven were virtually unaffected by the drug.

Animals↗
PubMed1985

Augmentation of interleukin 1 and interleukin 2 production by OK-432.

Intraperitoneal (i.p.) administration of OK-432 augmented both interleukin 1 (IL-1) and interleukin 2 (IL-2) production to the rechallenge of OK-432 in vitro. Peritoneal exudate cells (PEC) of mice 8 days after i.p. injection with OK-432 (1 KE/mouse) showed maximum IL-1 production to the restimulation with OK-432 in vitro. OK-432-induced IL-1 was consisted of three molecular weight species (two major peaks: 85 K and 15 K daltons and one minor peak: 67 K daltons) on Sephadex G-100 chromatography. Splenocytes of mice 4 days after i.p. injection with OK-432 (1 KE/mouse) demonstrated maximum IL-2 production to the in vitro rechallenge of OK-432, however, in vivo OK-432 administration failed to enhance ConA-induced IL-2 production in vitro. From gel filtration analysis, OK-432 induced IL-2 had an unique molecular weight (approximately 70 K daltons). From these results, OK-432-induced augmentation of cellular immunity against tumor cells might be due to the activation of so-called lymphokine cascade reaction mediated by IL-1 and IL-2.

Animals↗
PubMed1985

Recovery of corneal sensitivity in grafts following penetrating keratoplasty.

Corneal sensitivity was tested in 145 cases of clear corneal transplants using Cochet-Bonnet aesthesiometer. The central area of corneal transplants was found to be either completely anesthetic or markedly hypesthetic even 32 years following corneal transplantation, as exemplified in a patient who had surgery for keratoconus. Age, preoperative diagnosis, contact lens wear, diabetes, or length of postoperative period had no correlation with sensitivity in corneal grafts. In cases with a preoperative diagnosis of failed graft, even the peripheral recipient cornea was found to be relatively hypesthetic. The observations from this study that the central area of corneal graft never recovers normal sensitivity may have significant implications on the epithelial cell integrity of corneal grafts.

Adult↗
PubMed1985

Differential effects of recombinant human interferon-alpha A/D on expression of three types of Fc receptors on murine macrophages in vivo and in vitro.

Recombinant human interferon-alpha A/D (IFN-alpha A/D) is known to act on murine cells. We studied the in vivo and in vitro effects of pure IFN-alpha A/D on the surface expressions of the three types of murine macrophage Fc receptors (FcRI, II, III). Peritoneal macrophages obtained from BALB/c mice injected 24 h previously with IFN-alpha A/D showed increased expressions of FcRI and FcRII, because an enhanced capacity to bind monoclonal IgG2a- or IgG2b-coated sheep red blood cells was revealed. However, an optimal IFN-alpha A/D dose of a distinct narrow range was required to induce the maximum increase in each type of FcR. Furthermore, the antibody-dependent cellular cytotoxicity mediated by either FcRI or FcRII was also increased with the same optimal dose of IFN-alpha A/D. On the other hand, IFN-alpha A/D did not induce any change in the surface expression of FcRIII, which was demonstrated by the binding of monoclonal IgG3-coated sheep red blood cells. The in vitro treatment of peritoneal macrophages with IFN-alpha A/D also increased the FcRI expression. In contrast with in vivo treatment, however, IFN-alpha A/D treatment in vitro did not bring about any change in the FcRII expression. The FcRIII expression also remained unchanged with IFN-alpha A/D in vitro. Lymphokine-rich mouse spleen cell supernatants which contained natural IFN-gamma again enhanced the FcRI expression, but did not modulate the expressions of FcRII or FcRIII in vitro.

Animals↗
PubMed1985

Induction of interferon and activation of NK cells and macrophages in mice by oral administration of Ge-132, an organic germanium compound.

After oral administration of an organic germanium compound, Ge-132 (300 mg/kg), a significant level of interferon (IFN) activity was detected in the sera of mice at 20 hr and it reached a maximum of 320 U/ml at 24 hr. This IFN activity was lost after heat- or acid-treatment, suggesting that the induced IFN is of gamma-nature. The molecular weight of this IFN was estimated to be 50,000 daltons by gel filtration. The NK activity of spleen cells was increased 24 hr after the oral administration of Ge-132, and cytotoxic macrophages were induced in the peritoneal cavity by 48 hr. In the mice receiving an intraperitoneal (ip) injection of trypan blue or carrageenan 2 days before oral administration of Ge-132, neither induction of IFN nor augmentation of NK activity occurred, and X-ray irradiation of mice also rendered the mice incapable of producing IFN, all indicating that both macrophages and lymphocytes are required for this IFN induction. Both NK and cytotoxic macrophages appeared 18 hr after ip administration of the induced IFN with a titer as low as 20 U/ml. These facts suggest that both the augmentation of NK activity and activation of macrophages in mice after oral administration of Ge-132 are mediated by the induced IFN.

Administration, Oral↗
PubMed1985

Colloidal carbon as a combined ophthalmoscopic and microscopic probe of retinal and choroidal vascular integrity.

While studying an experimental retinal immunopathy, we searched for a vascular tracer that would permit us to test the anatomical and functional status of retinal and choroidal vessels by ophthalmoscopy, light microscopy, and electron microscopy in the same eye. We found that colloidal carbon, administered intravenously, can be seen ophthalmoscopically in the choroidal and retinal circulations, and abnormal deposits of it can be visualized in vivo. The ophthalmoscopic findings can be corroborated and extended by stereomicroscopy, and later the same specimens can be used for light and transmission electron microscopical studies. This tracer, thus, would allow the correlation of the ophthalmoscopic appearance of a clinical lesion with its histological and ultrastructural substrata.

Animals↗