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Biomedical subjects

M Iwata

Publications and source records attributed to M Iwata.

At least 415 records · Page 23Linked to original sources

[Experience of multimodal therapy for advanced neuroblastoma].

The prognosis of advanced neuroblastoma is extremely poor. We treated 5 patients with advanced neuroblastoma, older than 3 years, with multimodal therapy including intraoperative irradiation and autologous bone marrow transplantation. Elevated serum NSE and ferritin level and unfavorable histology according to the Shimadas histological classification, all of which are indicators of poor prognosis, were found in all of them. N-myc oncogene was amplified in 3 cases. After preoperative intensive induction chemotherapy, delayed primary operation and intraoperative irradiation (10-15 Gy) were performed. The postoperative lethal dose chemotherapy and total body irradiation (33 Gy x 3 days) were followed by autologous bone marrow transplantation. Tumor cells were purged using immunomagnetic beads method. Two cases showed recurrence (brain; 1, bone and bone marrow; 1) and a metastatic brain tumor was extirpated completely. All of them are alive during the follow up period from 6mo. to 4y8mo. (mean; 2y5mo.) with no evidence of disease except one. It may be concluded that our multimodal therapy is effective in achieving better results for advanced neuroblastoma.

Bone Marrow Purging↗

[A case of diffuse panbronchiolitis complicated by malignant thymoma and Sjögren's syndrome].

A patient with diffuse panbronchiolitis (DPB) complicated by malignant thymoma and Sjögren's syndrome with pseudolymphoma is reported. A 58-year-old woman developed productive cough, dyspnea and sicca in the mouth. Laboratory findings on admission indicated a high titer of cold hemagglutinin, positive of anti-DNA and negative PPD skin test. Chest-X ray revealed diffuse reticulonodular shadows in the lower lung field and anterior mediastinal mass shadow. Pulmonary function studies showed reduction of the vital capacity, forced expiratory volume in one second, DLco and hypoxia (PaO2; 69.1 Torr). Lung biopsy and resection were performed. Histologically infiltration of mononuclear cells and accumulation of foamy cells around respiratory bronchioles and stenosis of terminal bronchioles by granulation tissue was compatible with the diagnosis of DPB and the mediastinal tumor appeared to be a malignant thymoma invading to pericardium. Focal infiltration of lymphocytes was also recognized around the salivary glands (Sjögren's syndrome) and in the alveolar septa (pseudolymphoma). This case of DPB might have been associated with lymphoproliferative disorders.

Bronchiolitis↗

[Stevens-Johnson syndrome associated with Mycoplasma pneumoniae infection in an adult].

A case of Stevens-Johnson syndrome caused by Mycoplasma pneumoniae in a 34-year-old woman is presented. At first, she was admitted for treatment of pneumonia with cefuzonam. She was discharged in good health twelve days after admission. However, three days after discharge, she was admitted again with fever, erythematous lesions, oral ulcerations and exudative conjunctivitis. Because M. pneumoniae infection was confirmed by the presence of an elevated IHA titer, a clinical diagnosis of Stevens-Johnson syndrome associated with M. pneumoniae infection was made. Also, Mycoplasma CF antigen-lymphocyte stimulation test (LST) gave positive results, while the cefuzonam-LST was negative. Treatment with methylprednisolone and minocycline was initiated. Resolution of lesion was evident only after thirty days and then steroid therapy was discontinued. This association has rarely been reported in adults. M. pneumoniae infection should be considered in cases of Stevens-Johnson syndrome in adults with pneumonia.

Adult↗

Association of glycosylation-inhibiting factor with plasma membranes of T suppressor cell hybridomas.

The glycosylation inhibiting factor (GIF) was detected in EGTA extracts of the OVA-specific Ts cell hybridoma, 231F1 cells and 71B4 cells, which constitutively secrete GIF. The lymphokine in both culture supernatants and EGTA extracts failed to bind to OVA-Sepharose. Association of GIF with the plasma membrane was confirmed by surface labeling of the 231F1 cells with 125I. The major species of GIF in the extract was 14.4-kDa peptide as determined by SDS-PAGE, and was identical to that detected in culture supernatants. Pretreatment of the cells with monoclonal anti-GIF switched the cells from the formation of unglycosylated IgE-BF to the formation of glycosylated IgE-BF, indicating that the membrane-associated GIF is involved in the determination of the nature of IgE-binding factor during their biosynthesis. When the hybridoma was stimulated with OVA-pulsed APC, EGTA extracts of the cells contained GIF having affinity for OVA. The binding of the OVA-binding GIF in the EGTA extracts to OVA-Sepharose was inhibited by a synthetic peptide, which corresponds to amino acid residues 307-317 in the OVA molecule and represents the epitope recognized by TCR on the cells. The OVA-binding GIF in the extracts bound to the monoclonal anti-TCR-alpha chain, H-28-710 and the mAb 14-12, which is specific for the Ag-binding chain of effector type suppressor factor, and suppressed the in vivo antibody response of BDF1 mice to DNP-OVA in a carrier-specific manner. Evidence was obtained that indicated that the Ag-binding chain was associated with nonspecific GIF chain on the cell surface of the Ag-stimulated cells.

Animals↗

The concentration of tissue plasminogen activator and urokinase in plasma and tissues of patients with ovarian and uterine tumors.

The concentrations of tissue plasminogen activator (t-PA) and urokinase (UK) were measured in the plasma of patients with benign or malignant ovarian and uterine tumors. Plasma levels of t-PA were higher in patients with malignant ovarian and uterine tumors than in patients with benign tumors. Plasma UK levels were, however, not different between patients with ovarian and uterine tumors (benign or malignant) and normal persons. The concentrations of t-PA and UK of tissues of uterine myoma were lower than those in normal uterine muscular layer. UK levels of tissues of endometrial and cervical cancers were significantly higher than those in normal endometrium and uterine cervix, whereas t-PA levels were not different between these tumors compared with those in normal uterine tissues.

Female↗

A method to generate antigen-specific suppressor T cells in vitro from peripheral blood T cells of honey bee venom-sensitive, allergic patients.

Peripheral blood mononuclear cells of patients allergic to honey bee venom were stimulated with denatured bee venom phospholipase A2, and the antigen-activated T cells were propagated for 4 days by human IL-2 in the presence or absence of recombinant human lipocortin I. Upon antigenic stimulation with the denatured phospholipase A2 and autologous monocytes or by cross-linking of CD3 by anti-CD3 antibody, the activated T cells, which had propagated by IL-2 alone, formed N-glycosylated IgE-binding factors and glycosylation enhancing factor (GEF), while those propagated in the presence of lipocortin formed unglycosylated IgE-binding factors and glycosylation inhibiting factor (GIF). The GEF and GIF formed by the antigen- or anti-CD3-stimulated T cells had affinity for bee venom phospholipase A2 and could be purified by using anti-lipomodulin Sepharose. In the mouse lymphocyte system, the major cell source of GIF is antigen-specific suppressor T cells, and the antigen-binding GIF from the cells suppressed the in vivo antibody response in an antigen (carrier)-specific manner. In view of the findings in the mouse system, the present results may provide an immunological maneuver to generate allergen-specific suppressor T cells, and to obtain allergen-specific suppressor factor from T cell populations in the peripheral blood of allergic patients.

Annexins↗

Changes in urinary n-hexane metabolites by co-exposure to various concentrations of methyl ethyl ketone and fixed n-hexane levels.

To make clear how the n-hexane metabolism is modified by co-exposure with MEK, rats were exposed to various concentrations of MEK mixed with a fixed concentration of n-hexane. Twenty-four male Wistar rats were divided into four equal groups. Each group was exposed for 8 h to 2000 ppm n-hexane, 2000 ppm n-hexane plus 200 ppm MEK, 2000 ppm n-hexane plus 630 ppm MEK and 2000 ppm n-hexane plus 2000 ppm MEK, respectively. Free metabolites and the sum of free and conjugated metabolites of n-hexane were analyzed by gas chromatography. The main metabolite was 2-hexanol during the exposure and 2,5-hexanedione (2,5-HD) after the exposure in any group. The main metabolites, 2-hexanol and 2,5 HD, decreased in inverse proportion to the co-exposed MEK concentrations. The results suggest that augmentation of n-hexane neurotoxicity by MEK co-exposure could not be explained only by 2,5-HD. In addition, 2,5-HD is recommended as an index for biological monitoring of n-hexane exposure. However, one should be careful to evaluate the exposed n-hexane concentration by urinary 2,5-HD, because n-hexane metabolism could be largely modified by co-exposure with MEK.

Administration, Inhalation↗

Hormonal stimulation of tyrosinase activity in human foreskin organ cultures.

A human foreskin organ culture system has been developed to study the response of human skin to hormonal stimulation. Foreskins are maintained in culture on floating plastic supports which allows the epidermal surface to be exposed to air while the dermis is bathed in nutrient medium. Both black and white human foreskins can be maintained in organ culture for at least 1 wk with no change in the tissue structure or cell viability as determined by histochemical staining and by dopa reaction staining. Tyrosinase activity in both black and white human foreskin cultures decays markedly during the first 2 d of culture to a new steady state level which remains stable throughout the culture period. Both black and white foreskin cultures consistently demonstrate 2- to 10-fold increases in tyrosinase activity when treated with theophylline (1 mM). Approximately 90% of all skin cultures examined showed an increase in enzyme activity when treated with this phosphodiesterase inhibitor. Dibutyryl cAMP (0.1 mM) and [Nle4, D-phe7]-alpha MSH (10(-8) M), were also found to markedly stimulate tyrosinase activity in some skin cultures, whereas alpha-MSH and prostaglandin E1 produced only an inconsistent and small increase in the activity of the enzyme. Histamine (1 microM), vitamin D3 (1 microM), and retinoic acid (1 microM) failed to stimulate tyrosinase activity in either white or black foreskin cultures. This hormone-responsive organ culture system can be utilized to characterize the molecular processes responsible for the regulation of tyrosinase and pigmentation in human skin.

Alprostadil↗

Mitomycin C cross-resistance induced by adriamycin in human ovarian cancer cells in vitro.

We prepared Adriamycin-resistant cancer cells by exposing an ovarian serous cystadenocarcinoma cell line to the drug. The resistant cells also showed cross-resistance to a wide variety of other compounds, including vincristine, vinblastine, actinomycin D, daunorubicin, mitomycin C and carboquone. Against vincristine, the cells showed a greater than 5,000-fold increase in resistance, far surpassing their resistance to the selection drug. The resistant cells displayed a decrease in intracellular Adriamycin content and an increase in the mRNA of the mdr-1 gene coding for P-glycoprotein, with no amplification of the DNA. In revertant cells, resistance to Adriamycin was lost, but that to mitomycin C was maintained. Adriamycin resistance was partially overcome by the addition of verapamil or cyclosporin A, but cross-resistance to mitomycin C was not influenced at all. These results strongly suggest that the resistance to mitomycin C observed in our Adriamycin-resistant cells was due to some other mechanism than that causing multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Changes in plasma hormone levels during loss of hypoosmoregulatory capacity in mature chum salmon (Oncorhynchus keta) kept in seawater.

Returning chum salmon (Oncorhynchus keta) in northern Honshu Island, Japan, complete gonadal maturation while in the bay. Mature fish caught in the bay failed to survive in seawater for more than a week, whereas they adapted to fresh water efficiently. Mortality in seawater seems to be due primarily to an increased plasma osmolality. Maladaptation to seawater was more pronounced in the fish caught deep in the bay than those caught outside the bay, and also greater in females than in males. In close correlation with the increased plasma osmolality and electrolyte concentrations, plasma levels of cortisol and growth hormone increased in the fish kept in seawater. Cortisol and growth hormone may be secreted in response to the increased plasma osmolality and would not be the direct cause of the maladaptation to seawater. Plasma prolactin remained low in the seawater fish, indicating that the increased secretion of prolactin, a freshwater-adapting hormone, is not the cause of maladaptation to seawater either. On the other hand, when the fish caught in the river were kept in fresh water, an increase in plasma prolactin concentrations was seen, particularly in females, whereas no significant change was seen in plasma cortisol and growth hormone. Concentrations of 17 alpha,20 beta-dihydroxy-4-pregnen-3-one in the female and of testosterone in both the male and female were extremely high in the bay fish and decreased slightly but significantly after 7 days in fresh water. The gonadal steroids may have inhibitory effects on osmoregulation in the mature salmon in seawater.

Adaptation, Biological↗

Seasonal variations in the content of catecholamines in carp heart (Cyprinus carpio).

1. Seasonal changes in epinephrine and norepinephrine contents were demonstrated in ventricular muscle tissues of carp heart. 2. Patterns of changes in epinephrine and norepinephrine contents were similar; high during late spring-to-summer and low in winter; however, the fluctuation in epinephrine content was greater than that of norepinephrine. 3. Tyramine caused a positive inotropic effect in isolated electrically-stimulated ventricular muscles of carp heart. The inotropic effect was totally blocked by reserpine, reduced by propranolol, but not altered by atenolol. 4. These results suggest that the catecholamines released from sympathetic nerve terminals may contribute to the regulation of the seasonal change in the function of cardiac muscles in the carp.

Animals↗

Biochemical identification of glycosylation inhibiting factor.

Rat monoclonal antibody against mouse glycosylation inhibiting factors was obtained, and radiolabeled glycosylation inhibiting factors from the mouse T-cell hybridoma, 231F1 cells, were purified by using the monoclonal antibody and antilipomodulin antibody. Analysis of the affinity-purified lymphokine by PAGE demonstrated two proteins of 14.4 kDa and 41 kDa. Both proteins migrated similarly under the reduced and unreduced conditions, indicating that each of the two species consist of a single polypeptide chain. Biologic activity of the lymphokine was recovered by extraction of the proteins from gel slices followed by renaturation. Evidence was obtained that suggested the 14.4-kDa peptide was a degradation product of the 41-kDa molecules. The 14.4-kDa peptide was also recovered by extraction of the surface-labeled 231F1 cells with Ca2+ chelator, indicating that the glycosylation inhibiting factor is associated with the cell surface.

Animals↗

Effect of phospholipase A2 inhibitors on mouse T lymphocytes. II. Phospholipase A2 inhibitors induce T cell hybridomas and a T cell clone for the formation of glycosylation-inhibiting factor.

The mouse T cell hybridoma 12H5 cells constitutively form glycosylation-enhancing factor (GEF) and produce both IgE-potentiating factor and ovalbumin (OVA)-binding GEF upon antigenic stimulation with OVA-pulsed macrophages. Culture of the 12H5 cells either with nonspecific glycosylation inhibiting factor (GIF) or with a phospholipase A2 (PLA2) inhibitor, ONO-RS-082, stopped the formation of GEF and induced the same cells to form GIF. Induction of the GIF formation by a PLA2 inhibitor was observed even when the 12H5 cells had been treated with mitomycin C, indicating that the switching from the GEF formation to the GIF formation was not due to selective proliferation of a GIF-producing subclone. The OVA-binding GIF produced by the PLA2-inhibitor-treated, antigen-stimulated 12H5 cells binds to homologous antigen (ovalbumin), and shares both antigenic determinant recognized by the monoclonal antibody 14-30 and the lipomodulin-determinant with antigen-specific suppressor inducer factor (TsiF). The present experiments also showed that a typical helper T cell clone, D10, G4.1 cells, constitutively formed GEF and that preculture of the T cell clone with IL-2 and the PLA2 inhibitor switched the cells from the formation of GEF to the formation of GIF. Upon stimulation with antigen-pulsed macrophages, the inhibitor-treated D10.G4.1 cells formed GIF having affinity for conalbumin. The results indicated that the same T cells have the capacity to form either GIF or GEF under different conditions, and suggested that the GIF-producing suppressor T cells may be a phenotype of a subset of helper T cells. Switching of the same cells from the GEF formation to the GIF formation by the PLA2 inhibitor and the ability of the inhibitor to enhance GIF formation suggested that PLA2-inhibitory activity or GIF activity of TsiF is involved in the suppressor T cell cascade.

Aminobenzoates↗

Nevus pigmentovascularis.

We describe a rare case of nevus pigmentovascularis, consisting of disseminated nevus spilus, mongolian-spot-like maculae, port-wine stains, bilateral nevus of Ota, and cavernous hemangioma. Although nevus pigmentovascularis is generally recognized as a congenital disease in Japan, we were unable to find a similar presentation of it in English textbooks on dermatology and plastic surgery.

Adult↗

The relationship between tyrosinase activity and skin color in human foreskins.

Tyrosinase activity was assayed in black and white human foreskin samples by measuring both the hydroxylation of tyrosine to dopa (tyrosine hydroxylase activity) and the conversion of [14C]tyrosine to [14C]melanin (melanin synthesis assay). Enzyme activity was found both in the particulate (75%) and soluble (25%) fractions of the cell. Membrane-bound tyrosinase was readily solubilized by either zwitter-ionic or nonionic detergents. The anionic detergent, sodium cholate, inhibited enzyme activity. Tyrosinase activity in black foreskin homogenates averaged almost three times that in white skin samples (33.8 pmols 3H2O/h/mg skin in black and 12.71 pmoles 3H2O/h/mg skin in white skin), although considerable overlap in activities existed among the two groups. Tyrosinase activities measured with two separate assays, tyrosine hydroxylase and [14C]melanin assays, were similar, suggesting that tyrosine hydroxylase activity is tightly coupled to melanin synthesis. Tyrosinase activity determined by either assay method generally correlated with skin melanin content. Kinetic analysis of tyrosinase from black and white foreskin revealed a Km for tyrosine of 2.5 X 10(-4) M in both skin types. Immunotitration experiments suggested that the difference in tyrosinase activities between white and black skin may be due, not only to different amounts of enzyme present in the melanocytes, but also possibly to differences in the catalytic activities of the enzyme found in melanocytes of black and white skin.

Black People↗

[A rat model of chronic bronchiolitis due to Pseudomonas aeruginosa--a histopathological study of bronchus-associated lymphoid tissue (BALT)].

To investigate the role of BALT in chronic respiratory infection, we established a rat model of chronic bronchiolitis caused by Pseudomonas aeruginosa, and the light microscopic findings of the BALT were studied. Experimental pneumonia was produced in SD rats by intratracheal inoculation of 10(6) colony forming units (cfu) of mucoid P. aeruginosa enmeshed in agar beads. The mean cfu recoverable from the lung increased up to 10(8) cfu at day 1. The number of bacteria remained fairly constant at 10(4) cfu until day 28. Histologically, infiltration of neutrophils could be seen around the agar beads containing P. aeruginosa in the lung from day 1 to day 7. From day 14 to day 28. the histological changes in the lungs were characterized by accumulation of foamy cells accompanied with lymphocyte infiltrations and granulation tissues around the respiratory bronchioles, but without involved alveoli. These chronic inflammatory histologic changes were similar to those of diffuse panbronchiolitis (DPB). At the same time, there were massive accumulation of lymphocytes in lymphatics and in high endothelial venules of the BALT at day 7. The development of germinal centers in the follicular area was found from day 7 to day 28. The airway was narrowed as a result of BALT hyperplasia protruding to the bronchial lumen. These results suggest that histological changes represent the model of chronic bronchiolitis and BALT may have a specific role in developing the local immune responses against chronic respiratory infection due to P. aeruginosa.

Animals↗

Suppression of tumor necrosis factor alpha production by a human immunoglobulin preparation for intravenous use.

We investigated the effect of a pH 4-treated human immunoglobulin preparation for intravenous use (pH4-G) on the production of tumor necrosis factor alpha (TNF-alpha) in vivo. The level of TNF-alpha in the sera of rabbits receiving pH4-G before lipopolysaccharide (LPS) injection was lower than that in rabbits receiving only LPS. Similarly, the in vitro production of TNF-alpha was suppressed by pH4-G. Rabbit peritoneal exudate cells stimulated with LPS in the presence of pH4-G produced less TNF-alpha than did those stimulated only with LPS. pH4-G, however, had no effect on various TNF-alpha activities, such as cytotoxicity against tumorigenic murine fibroblasts (L929 cells), induction of interleukin-1 production, or fever induction. These results indicate that pH4-G suppresses TNF-alpha production without affecting TNF-alpha activities. A suppressive effect on the expression of TNF-alpha mRNA was also observed.

Animals↗

Therapeutic efficacy of granulocyte colony-stimulating factor alone and in combination with antibiotics against Pseudomonas aeruginosa infections in mice.

The therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) against an experimental intramuscular infection induced by Pseudomonas aeruginosa in mice was confirmed. Bacterial growth in the infected thigh muscle was suppressed by G-CSF treatment. The change in the number of peripheral blood polymorphonuclear leukocytes (PMN) after bacterial challenge was investigated. The results showed that G-CSF could stimulate stronger defense mechanisms after stimulation by bacterial challenge. In the G-CSF-treated group, more clusters of matured PMN were observed in the infected thigh muscle 6 h after bacterial challenge. Next, the correlation between the number of PMN in the blood at the time of infection and the therapeutic efficacy of antibiotics was investigated. The therapeutic efficacy of ceftazidime, a beta-lactam antibiotic, was affected by the number of blood PMN at the time of infection. In particular, a decrease of peripheral blood PMN at the time of infection resulted in a dramatic decrease in the efficacy of ceftazidime. The reduction in leukopenia by G-CSF remarkably strengthened the therapeutic effect of antibiotics in mice.

Animals↗