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Biomedical subjects

M Sakumoto

Publications and source records attributed to M Sakumoto.

At least 37 records · Page 2Linked to original sources

Autologous tumor cell killing activity of tumor-associated lymphocytes in patients with head and neck carcinomas.

In order to select the most cytotoxic effector cells for adoptive immunotherapy, lymphokine activated killer (LAK) cells, tumor infiltrating lymphocytes (TILs) and autologous mixed lymphocyte tumor cell culture (MLTC) cells derived from peripheral blood mononuclear cells (PBMC) in the same subject with head and neck carcinomas were prepared. The autologous tumor cell killing activity and cell surface phenotypes of each of the three effector cells were studied. MLTC cells cultured with interleukin-2 (IL-2) showed the strongest cytotoxic activity among these three different effector cells. Although TILs had suppressed killing activity immediately after isolation, after successive cultivations with IL-2, a cytotoxic activity against autologous tumor cells stronger than that of LAK cells appeared. Both IL-2 stimulated MLTC cells and TILs showed an enrichment of CD8 positive and CD11 negative cells in a CD3 positive subpopulation.

Antigens, Surface↗

The synergistic effects of interleukin 2 and interleukin 7 on the proliferation and autologous tumor cell lysis of tumor-associated lymphocytes.

Interleukin-7 (IL-7) has an ability to stimulate the proliferation of pre-B cells. It has been shown that IL-7 can also activate T lymphocytes. We here demonstrate that IL-7 in combination with interleukin-2 (IL-2) can drive cell proliferation and enhance the autologous tumor cell lysis by peripheral blood mononuclear cells (PBMC) and autologous mixed lymphocyte tumor cell culture (MLTC)-derived effector cells (MLTC cells). These synergistic effects of IL-2 and IL-7 on the proliferation and the augmentation of autologous tumor cell lysis were found for both effector cells. These effects were inhibited by neutralizing antibodies to IL-2 or IL-7, and by a combination of both antibodies, significantly. In terms of phenotypical expression, CD3 positive cells comprised the vast majority of MLTC cells after culture in medium containing IL-2 and IL-7 with an increase of IL-2 receptor positive cells.

Cell Division↗

The hazards of alkaline disk batteries as foreign bodies in the nose.

This paper reports a case of intranasal chemical burn and septal perforation caused by an alkaline disk battery accidentally entrapped in the nasal cavity of a 3-year-old girl. The battery in the nasal cavity was removed after about 44 hours, but nasal septal perforation without nasal deformity occurred about 3 weeks after accident.

Burns, Chemical↗

[The expression of ICAM-1 on head and neck squamous cell carcinoma cell lines].

Intercellular adhesion molecule-1 (ICAM-1) is one of the cell adhesion molecules. This molecule is a glycoprotein of about 90 KDa belonging to the immunoglobulin (Ig) superfamily and is widely expressed by hematopoietic and non-hematopoietic cells which play a role in the immune system. ICAM-1 is also a ligand or counter-receptor for the leukocyte integrin lymphocyte-function associated antigen-1 (LFA-1). We investigated the expression of ICAM-1 on the surfaces of cells from fifteen head and neck squamous carcinoma cell lines and the modulation of ICAM-1 expression by IFN-gamma, using an immunohistochemical stain. We categorized four types of stain degree. (-): < 10% of cells positive (+/-): 10-40% of cells positive (+): < 40-70% of cells positive (++): > 70% of cells positive Four cell lines showed (-) type. Three cell lines: (+/-). One cell line: (+). Seven cell lines: (++). The primary site of cell lines and the degree of ICAM-1 expression were not detectable. Connection between pathological differentiation and the degreed expression were not apparent, either. IFN-gamma up-regulated the degree of ICAM-1. All cell lines, when stimulated by IFN-gamma, showed (++) type.

Carcinoma, Squamous Cell↗

Sequential appearance of host-derived T cell subsets during differentiation in nude mice grafted with rat fetal thymus.

To elucidate the abnormality of T cell differentiation in nude mice grafted with rat fetal thymus that develop multiple-organ-localized autoimmune diseases, we examined sequential appearance of T cell subsets and expression of TCR genes in BALB/c nude mice after grafting with fetal F344 rat thymus. We observed progressive expression of TCR gamma/delta-alpha/beta genes in the lymph node (LN) cells from 8 to 12 wk after grafting. An appreciable number of CD4+ T cells but few CD8+ T cells were detected in the LN at 8 wk after grafting. CD8+ T cells increased slowly in number by 12 wk after grafting but remained at a low level in comparison with those in nude mice 12 wk after grafting with BALB/c thymus. In correlation with an increase in the number of T cells expressing TCR alpha/beta genes, alloreactivity as assessed by MLR was increased to a normal level. However, CTL activity against alloantigens remained at a low level in the LN cells at 12 wk. At this stage, organ-specific autoimmune diseases and a high level of anti-DNA autoantibodies were detected. In these mice host-reactive T cells such as V beta 3- or V beta 11-bearing T cells were virtually eliminated in the peripheral mature T cell pool, whereas T cells maturing in the fetal rat thymus significantly proliferated in response to donor-rat stimulator cells. These results suggest that the development of the autoimmune diseases may be ascribed to an impaired maturation of CD8+ T cells but not to failure in clonal elimination of host-reactive T cells in nude mice grafted with rat thymus.

Animals↗

In vivo treatment with anti B-220 monoclonal antibody affects T and B cell differentiation.

The B220 cell marker is expressed on B cells and on T cell precursors. In order to determine the involvement of the B220 antigen on murine lymphoid differentiation, we treated 5-10-week-old mice periodically with a specific anti-B220 antibody, RA3-6B2, a non-cytolytic IgG2b. After the third injection, a significant reduction (P less than 0.02) in the number of thymocytes and less dramatically in the number of splenocytes was observed. This reduction was predominantly due to a decrease of cells carrying the following markers: Thy-1.2+, Lyt-1+, Lyt-2.3+, L3T4+, and asGM1+. Mitogenic response to concanavalin A, phytohaemagglutinin and lipopolysaccharide, mixed lymphocyte reaction, cytotoxic T cell activity, and plaque-forming cell generation were significantly decreased after the treatment (P less than 0.01). These results show that the in vivo treatment with anti-B220 monoclonal antibody reduced the number of T and B cells and modified their functional activity. This suggests that the B220 antigen is involved in the maturation of both T and B cells.

Animals↗

[Evaluation of turnover of olfactory epithelium in mice by using anti-BrdU monoclonal antibody].

Among nerve cells of vertebrates, the olfactory elements are uncommon in their capacity to turnover and to be replaced after injury. An autoradiographical and morphological observation has shown that degenerated olfactory nerve cells are reconstituted by a new population of neurons which originate from basal cells. However, an autoradiographic method requires a special isotope institute and it takes a long time for the final specimen to observe. Recently, a rapid technique without the radioisotope has been alternatively developed in which a thymidine analogue, 5-bromo-2'-deoxyuridine (BrdU), is incorporated into replicating DNA and subsequently localized using a specific monoclonal antibody. In the present study, cell dynamics of olfactory mucosa in mice were investigated by means of immunohistological technique. The results were as follows. 1. The labelled elements were concentrated at the basal layer of the epithelium, which were observed 5 hrs after the first injection of BrdU. 2. At 15 days after administration of BrdU, the labelled elements were located in the mid-layer of the epithelium, where can be recognized as the compartment of nerve cells. 3. After 30 days, the labelled cells disappeared from the epithelium. It indicates that the period of turnover in the olfactory epithelium of mice is within 30 days. 4. Fifteen days after axotomy of the olfactory nerves, two stained patterns which were numerously or sparsely labelled regions were observed. The former is considered that immature neurons predominantly exist, and the latter is the area which mature neurons abundantly locate. It is considered that this immunohistological approach is useful for the observation of the turnover of the olfactory epithelium.

Animals↗

Deletion of Mls-reactive T cells in H-2-compatible but Mls-incompatible bone marrow chimeras.

The cellular basis of tolerance induction to Mls-encoded antigens in radiation bone marrow (BM) chimeras has been investigated in two H-2-compatible strain combinations of AKR/J (H-2k, Thy-1.1, Mls-Ia) and C3H/He (H-2k, Thy-1.2, Mls-IIa). Sequential appearance of host- and donor-derived T cell subsets and T cell receptor gene messages occurred in the peripheral lymphoid organs of both irradiated AKR/J mice reconstituted with C3H/He BM cells (C3H/He-AKR/J chimera) and irradiated C3H/He mice reconstituted with AKR/J BM cells (AKR/J-C3H/He chimera). A large number of cells expressing T cell receptor gamma genes were detected in spleen on day 21 after reconstitution, while the normal level of alloreactivity was first detected in the spleen on day 56 after reconstitution in correlation with the appearance of appreciable levels of Thy-1 high cells and T cell receptor alpha and beta gene transcripts. T cells bearing V beta 6, that is strongly correlated with reactivity to antigens encoded by the Mls-Ia genetic locus, were virtually abolished in spleen on day 56 in both C3H/He-AKR/J chimera and AKR/J-C3H/He chimera. Furthermore, expression of V beta 3 gene transcripts, that are important for recognizing Mls-IIa, was undetected either in the peripheral lymphoid cells of AKR/J-C3H/He chimera or in those of C3H/He-AKR/J chimera. These results suggested that clonal elimination of self-reactive T cells bearing V beta 3 or V beta 6 was induced by both host-derived radioresistant cells and donor-derived repopulating cells in the thymus of radiation BM chimeras.

Animals↗

The effect of T cell depletion from spleen cell allografts on graft-versus-host disease and long-term immune reconstitution in H-2 haplotype-identical murine combinations.

Graft-versus-host disease (GVHD) and states of immune reconstitution in allogeneic chimera mice across minor histocompatibility antigens were analyzed in excess of 9 months after injecting AKR/JSea (AKR) spleen cells into irradiated C3H/HeSlc (C3H) mice. When T cell-depleted AKR spleen cells were used as inoculum cells, neither graft failure nor GVHD was seen for 9 months postgrafting in the C3H mice irradiated with 660 rad or more. In an AKR - C3H (850 rad) model, Thy1.1+ or L3T4+ T cell depletion from donor AKR spleen cells abolished both acute and chronic GVHD in lethally irradiated C3H mice. Lyt2+ T cell depletion, however, resulted in acute and chronic GVHD in more than half of the recipient C3H mice. Moreover, actual existence of donor (AKR)-type T cells with L3T4 phenotype, but not Lyt2 phenotype, was always observed in the spleen of the C3H mice suffering from acute GVHD. In addition, the C3H mice that were irradiated with 850 rad, grafted with AKR spleen cells depleted of Lyt2.1+ T cells, escaped from acute GVHD and survived for more than 10 mo postgrafting, showed impaired activities of immune responses such as delayed footpad reaction to sheep red blood cells, antibody production tested by IgM plaque forming cells and reactivity to an intracellular bacterium. Listeria monocytogenes as compared with the C3H mice reconstituted with syngeneic C3H spleen cells or Thy1.1+ or L3T4+ T cell-depleted AKR spleen cells. These results suggest that L3T4+ T cells, rather than Lyt2+ T cells, contained in the grafted cells not only cause acute GVHD but also a long-term immunodeficient state (chronic GVHD) in recipient mice in the H-2-identical murine combinations examined here.

Animals↗

Three cases of inter-sterno-costo-clavicular ossification associated with tonsillar infection.

Three cases of inter-sterno-costo-clavicular ossification (ISCCO) associated with chronic tonsillitis are reported. Two cases had additional symptoms of pustulosis palmaris et plantaris (PPP). All the patients underwent tonsillectomy. The histological changes of the palatine tonsils of case 1 and case 2 were characterized by so-called focal small lacunar ulcers and periarteriolar fibrosis (onion-skin lesion). Some multinucleated giant cells were observed in case 2. Following tonsillectomy, symptoms in the clavicular region and the PPP improved. It is possible to consider that ISCCO is caused by focal tonsillar infection.

Adult↗

In vivo influence of the anti-B220 monoclonal antibody administration of the T cell differentiation in mice.

B220, a pan-B marker, is known to be also expressed on immature T cells of MRL/1pr or other congenic 1pr mice and minor population of immature thymocytes but not on peripheral T cells. In this study, we investigated in vivo the possibility whether B220 is one kind of premature T or prethymic T precursor cell marker as well as a pan-B cell marker. A monoclonal antibody against B220 glycoprotein was intravenously injected every 2 days into various strains of mice. After the third administration of this antibody, thymocytes decreased remarkably compared with those from the rat IgG-treated group, and spleen cells were also reduced significantly. Further, the number of cells expressing Thy-1, Ly-1, Lyt-2, and asialo GM1 (asGM1) in the spleen were significantly reduced. On the contrary, the number of cells expressing surface IgM (sIgM) or B220 were increased by this treatment, especially after the 8th treatment. Some T-dependent immunological functions including mitogenic responses to lectins and cytotoxic T cell activity were markedly suppressed but mixed lymphocyte reaction (MLR) and natural killer (NK) activity were rather augmented. Thus, B220 may be expressed on some kinds of T cell progenitor. Taken together, in vivo treatment with anti-B220 antibody may influence differentiating stages of some T cells from bone marrow progenitors before or just after their homing into the thymus.

Animals↗

Epstein-Barr virus (EBV) infection by cocultivation of fibroblast-dominant cell line and EBV-transformed lymphocytes.

A long-term cell culture epitheloid cell line (NPC-F/L) was established from the fibroblast-dominant cell line derived from nasopharyngeal carcinoma tissue by cocultivation with an Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line of adenoid origin. The cells were investigated by karyotyping, by immunofluorescent testing for EBV-associated nuclear antigen (EBNA), early antigen (EA), and viral capsid antigen (VCA) and by a light microscopy. The cells were shown to be epithelial not only by morphology but also by immunocytochemical staining with monoclonal antibody to cytokeratins and they expressed EBNA and EA but not VCA. The cells developed histologically undifferentiated squamous cell carcinoma when inoculated subcutaneously into the back of athymic nude BALB/c(nu/nu) mice, which were similar to the human tumors from which the fibroblastoid cell line was established. The presence of EBNA in touch smears prepared both from the biopsy tissue of human and nude mice was demonstrated. Karyotyping analysis indicated an aneuploid chromosome with a model number of 74.

Cell Line↗

[Experimental study on the effect of the topical application of steroids on olfactory disturbance in mice].

Although the topical treatment with steroids is the widespread method for olfactory disorders in human, the reports are limitted to clinical observations. The aim of this report is to evaluate the effect of topically applied of steroids in mice on the repairing course by the experimental olfactory disorders caused by zinc sulfate. The olfaction of mice was estimated by the record of behavioral task, using Cycloheximide, commonly used as repellent in rodents. When mice taste Cycloheximide for the first time, immediately the mice experience a very disagreeable taste leading to the simultaneous memory of the odor of Cycloheximide. Those who once experienced the taste and odor of Cycloheximide, will avoid simply by the odor next time. Two bottles were offered to mice, one containing distilled water and the other 0.01% Cycloheximide. When the mouse drank the distilled water, the response was interpreted as a correct response. When the Cycloheximide solution was chosen, an error. Twenty four mice were tested at ten times during a 10-minute trial, and the rates of correct response were counted. From the next day after the treatment of zinc sulfate, nasal application of 0.1% beta-methasone (group A), or nasal application of distilled water (group B) were applied to each group of twelve mice for five days. The results were as follows. 1. In the first experiment, the correct response was 85% (group A), and 80.8% (group B), however at the second trial, all responses were correct.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

Treatment of autoimmune MRL/lpr mice with anti-B220 monoclonal antibody reduces the level of anti-DNA antibodies and lymphadenopathies.

The predominant accumulating cells in the lymphoid tissue of MRL/lpr mice have been shown to carry the B220 cell marker. This antigen is expressed on B cells and on T-cell precursors. In order to know the pathogenic involvement of cells carrying this marker, we treated MRL/lpr mice periodically with RA3-6B2, a specific anti-B220 monoclonal antibody, or rat IgG2b as a control. After 12 weeks of treatment, a significant reduction (P less than 0.01) in the size of the lymph nodes and spleen was observed only in the group treated with RA3-6B2 monoclonal antibody. This reduction was mainly due to a decrease in the Thy-1.2+ and B220+ subpopulations. Anti-DNA and anti-Sm antibody titres were also reduced significantly (P less than 0.01) after the therapy. Proliferative response to mitogens (Con A, PHA, LPS) and IL-2 production was not improved after the anti-B220 treatment. These results suggest a pathogenic role of lymphocytes carrying the B220 marker in the autoimmune disease of MRL/lpr mice.

Animals↗

Preventive effect of dapsone on renal scarring following mannose-sensitive piliated bacterial infection.

Renal scarring has been thought to occur in the later stages of chronic pyelonephritis. We previously reported that mannose-sensitive (MS) piliated bacteria promoted renal scarring, which was prevented by antioxidants. The preventive effect of diaphenylsulfone (dapsone), which has a scavenging activity on active oxygen species, on renal scarring was examined. Female Sprague-Dawley rats were inoculated with clinical isolates of Serratia marcescens which had both MS and mannose-resistant pili or with recombinant strains which had MS pili on their surface; they were then administered 20 mg/kg of dapsone or not. Dapsone significantly suppressed scarring following infection of the kidney. The bacterial counts in the kidneys were not different in dapsone-treated and nontreated rats. We conclude that dapsone is effective in preventing renal scarring, and it is suggested that the clinical use of this drug may prevent renal scar formation following pyelonephritis.

Animals↗

Enhanced chemiluminescence response of polymorphonuclear leukocytes by new quinolone antimicrobials.

Some of the many antimicrobial agents (beta-lactams, macrolides, aminoglycosides, tetracyclines, new quinolones; NQs) were reported to have a bactericidal or bacteriostatic effect cooperating with host defense mechanisms including polymorphonuclear neutrophils (PMNs). We investigated the effect of new quinolone antimicrobials on chemiluminescence (CL) response of human PMNs. Among many NQs, we chose ofloxacin, lomefloxacin, fleroxacin, sparfloxacin, AM-1155, NM-394, Q-35, Y-26611 and T-3761. Twenty-five or 100 micrograms/ml of fleroxacin and ofloxacin enhanced luminol-dependent CL response of PMNs up to 1.5-2.0 times compared to the drug free condition. Other antimicrobial agents, however, inhibited CL response. This suggested that fleroxacin and ofloxacin were more efficient in the treatment of bacterial infections with respect to the interaction between antimicrobials and PMNs.

Anti-Infective Agents↗