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Biomedical subjects

M Torisu

Publications and source records attributed to M Torisu.

At least 73 records · Page 4Linked to original sources

Potential role of Kupffer cells in initiating liver injury during endotoxemia.

The potential contribution of Kupffer cells (KCs) to endotoxin-induced liver damage was evaluated by measuring the functional changes of KGs [Superoxide (O2-) generation, and chemotaxis (CTx)] isolated from such livers and comparing them with biochemical and histological changes of liver damage. Sublethal doses of endotoxin was daily administered to rats for 4 days. Liver damage was apparent in the rats treated with single administration of endotoxin and the maximal change was observed in the rats treated with endotoxin for 2 days in association with the marked enhancement of O2- release and CTx in vitro by KCs from these animals. However, liver injury decreased in the rats treated with endotoxin for 3 days and the rats treated with endotoxin for 4 days had shown almost no detectable injury. KCs' biological functions also diminished in group treated for 3 and 4 days. In particular, oxidative and chemotactic responses of KCs from rats treated for 4 days significantly decreased, compared with the cells from those treated for only two days. These results indicate that KCs are pivotal in the pathogenesis of liver injury during endotoxemia.

Animals↗

Staining of surface antigen on migrating lymphocytes in the chemotaxis membrane. I: Complement C5 attracts helper/inducer T cell much more than suppressor/cytotoxic T cell and NK cell.

We have measured various chemotactic activities for neutrophils (1-3), lymphocytes (4), macrophages (5) and eosinophils (6-11) by the modified Boyden chamber method. In the conventional method, it is necessary to purify the indicator cells in upper chamber because it is impossible to distinguish inflammatory cells on the chemotactic membrane. For example, when we estimate T lymphocyte chemotaxis, we collected nylon-wool nonadherent peripheral blood lymphocytes (PBL) and confirmed their purity by sheep erythrocytes rosette formation assay. Pohajdak et al (12) evaluated NK cell chemotaxis by using large granular lymphocytes (LGL) for indicator cells. LGL fractionation was confirmed by monoclonal antibodies, HNK-1, OKT11, OKT3, OKT4, OKT8, OKM1, and MO2. When we arranged the study to evaluate chemotaxis of lymphocyte subsets which were divided by surface antigens, the conventional method needed a large quantity of PBL for the indicator cells. Moreover, one or two lymphocyte subsets had to be obtained from an identical PBL donor. This was time consuming. So, we tried to identify migrating lymphocytes in the chemotaxis membrane by their surface antigens. In this communication, we report that the staining of surface antigens on migrating lymphocytes in the chemotaxis membrane is effective and useful for evaluation of lymphocyte subset chemotaxis. It prompted us to report the new findings about modification of lymphocyte subset chemotaxis by C5a.

Antigens, Differentiation, T-Lymphocyte↗

Highly purified murine interleukin 5 (IL-5) stimulates eosinophil function and prolongs in vitro survival. IL-5 as an eosinophil chemotactic factor.

The recent molecular cloning of the complementary DNA encoding T cell--replacing factor (TRF) has demonstrated that a single molecule is responsible for B cell growth factor II (BCGF-II) activity and eosinophil differentiation activity. It has been proposed that this molecule be called interleukin 5 (IL-5). We previously reported that purified rIL-5 supports the terminal differentiation and proliferation of eosinophilic precursors. In this study, we examined the effects of IL-5 on functional activities of mature eosinophils. IL-5 maintained the viability of mature eosinophils obtained from peritoneal exudate cells of mice infected with parasites. It also induced superoxide anion production in a dose-dependent manner. The Boyden's chamber Millipore assay revealed that IL-5 had a marked chemokinetic effect on eosinophils in a dose-dependent manner. Moreover, IL-5 was found to be an eosinophil chemotactic factor by the checkerboard assay. In conclusion, IL-5 is suggested to play an important role in increasing the functional activities of eosinophils as well as their production in allergic and parasitic diseases.

Animals↗

Symptomatic accessory lobe of the liver associated with hyperthyroidism.

A case of symptomatic accessory lobe of the liver occurred in a 15-year-old Japanese girl with hyperthyroidism. The patient presented with acute abdominal distress; at operation, a twisted necrotic mass of the accessory lobe of the liver was found. A review of the literature failed to show a previously reported instance in a child.

Adolescent↗

Ischemic colitis in a 33-year-old woman on danazol treatment for endometriosis.

A 33-yr-old Japanese woman, married, no parity, was treated for endometriosis. Danazol 400 mg a day was initiated on September 25, 1986, for 21 consecutive days. She became severely constipated and had left lower abdominal colic pain. Five days later, she had to be admitted to the hospital, because she had had no bowel movements for 12 days and the abdominal pain was severe. On the day after admission, she had frequent painful bowel movements. The stool was blood-tinged, but pathogenic bacteria were nil. Ischemic colitis of the stricture type was identified. She was treated with hyperalimentation and anticholinergic agents. At 3 months and 5 days after discharge from hospital, danazol 400 mg per day was readministered, and 11 days later, the patient again became constipated and complained of the same pain in the left flank. We consider that danazol-induced constipation played a role in the onset of the ischemic colitis.

Adult↗

[Prevention of immunodeficiency induced by cancer chemotherapy with BCG].

MFC (MMC, 5-FU and cytosine-arabinoside) therapy applied with the liver organism Bacillus Calmette-Guérin (BCG) for the treatment of postoperative patients with cancer of the digestive organs presenting at stage II and III. Immunological parameters included skin reaction by purified protein derivative (PPD), lymphatic blastogenesis test using phytohemagglutinin (PHA) and lymphatic subsets. The frequency of MFC therapy was significantly higher in the MFC plus BCG group than in the MFC group (p less than 0.001). At the completion of MFC therapy, both of PHA blastogenesis rate, OKT4/OKT8 and OKT3 were all within the normal limits. The PPD skin reaction was positive (18.2 +/- 4.0mm) as before the start of MFC therapy. These results suggest that BCG immunotherapy may potentiate the effect of chemotherapy.

Aged↗

A chemotactic factor for rat thymocytes may regulate T-lymphocyte migration toward the thymic microenvironment.

Using a modified Boyden chamber assay, extracts or culture supernatants of rat thymic stromal cells, or thymocytes were examined by chemotactic activity to rat leukocytes. Rat thymocytes responded chemotactically to the aqueous extract as well as to culture supernatants of thymic stromal cells. However, neither the extract and culture medium from concanavalin A-stimulated thymocytes nor any component of rat serum has shown such an activity. The thymic extract was fractionated into three molecular species with chemotactic activity for thymocytes. The thymocyte chemotactic factor(s) (TCFs) in the extract was distinct from known lymphocytic chemotactic factors, such as interleukin-1 (IL-1), IL-2, C5a, and the culture supernatant of stimulated thymocytes. In vitro, TCFs could attract, in addition to thymocytes, bone marrow cells, fetal liver cells, and nylon-wool nonadherent lymphocytes from peripheral blood and spleen. Lymph node cells, neutrophils, macrophages, and B cells from peripheral blood could not respond to TCFs. Thymocytes also responded to the extract of splenic stromal cells. Unlike the thymic extract, however, the splenic extract was chemotactically active for lymphocytes from lymph nodes but not for bone marrow cells. These results indicate that thymic stromal cells secrete a chemotactic factor(s) for a relatively immature type of T-lineage cells, which may by a thymus-homing progenitor T cell, while spleen may contain an attractant for a relatively mature type of T-lineage cells.

Animals↗

Neutrophil-mediated tumor cell destruction in cancer ascites. II. A OK-432 attracts killer neutrophils through activation of complement C5.

When a streptococcal preparation, OK-432, was administered intraperitoneally to patients with malignant ascites, the number of neutrophils with cytotoxic activity against tumor cells was increased in the peritoneal cavity immediately after the OK-432 injection. In order to investigate the underlying mechanisms of such neutrophil accumulation, a possible neutrophil chemotactic activity in ascitic fluid was assayed by a modified Boyden method. The chemotactic activity for neutrophils was found significantly higher 6 hr after the OK-432 injection. OK-432 along had no direct chemotactic activity for neutrophils. The chemotactic activity was generated in vitro when ascitic fluid from patients without OK-432 treatment was incubated with OK-432 for 30 min at 37 degrees C. However, preheating of the fluid at 56 degrees C for 30 min or the addition of EDTA to the fluid resulted in the failure of generation of the chemotactic activity after the incubation with OK-432. The addition of EGTA did not show a significant effect. The chemotactic activity in ascitic fluid was found near cytochrome c marker (MW 12,400 D), when fractionated by Sephadex G-200 gel chromatography. The chemotactic activity was heat stable, nondialyzable, and neutralized completely with anti-human complement C5 antibodies. These results suggest that C5a generated via the alternative pathway activated by OK-432 may be responsible for the infiltration of killer neutrophils in the peritoneal cavity in patients with malignant ascites when they are treated by the intraperitoneal injection of OK-432.

Adult↗

[Management of malignant ascites by intraperitoneal injection of OK-432. Possible mechanism of the reduction of original tumor mass volume].

We studied the effect of intraperitoneal injection of OK-432 on the growth of original tumor mass in patients with malignant ascites and a possible mechanism of reduction of tumor volume. Sixteen patients with valuable original tumor mass and a large amount of ascites caused by gastro-intestinal cancer were studied. Tumor cells were separated from ascitic fluids and cultured in vitro before the study. Lymphocytes were collected from the fluids at varying intervals after intraperitoneal injection of OK-432 and cultured 24 hours in vitro. Effect of the culture supernatant on ascites-derived autologous tumor cell growth was examined in vitro using microplate assay. The results were as follows. 1) Reduction of tumor mass more than four weeks was found in 4 of 16 cases. 2) Before OK-432 injection, the culture supernatant from ascites-derived lymphocytes did not inhibit autotumor cell growth in vitro. But, the supernatant from lymphocytes which were collected from the ascites after OK-432 injection markedly inhibited tumor growth in all of 4 tumor mass reduction cases. In 12 non-reduction cases the supernatant slightly inhibited tumor growth only in 2 cases. 3) A similar growth inhibitory factor was detected in the mixed culture-supernatant of peripheral blood lymphocytes and OK-432 in vitro. 4) Preliminary studies indicated that the tumor growth inhibitory factor might be different from tumor necrosis factor and interferons. These results indicate that ascites-derived lymphocytes-producing factor may play an important role in reduction of tumor mass volume in patients with cancerous ascites.

Adenocarcinoma↗

[The management of malignant ascites with a streptococcal preparation, OK-432: relation between the clinical effect and auto-tumor cell killing activity by OK-432-induced ascites-derived lymphocytes].

Twelve patients with malignant ascites caused by gastro-intestinal cancer were treated by intraperitoneal administration of OK-432. Tumor cells from these patients were separated from ascitic fluid and cultured in vitro before OK-432 therapy. OK-432 was given intraperitoneally one to two times a week at doses ranging from 5 to 20 KE suspended in saline. Mononuclear lymphocytes were collected from the fluid at various intervals throughout the therapy. The effect of ascites-derived lymphocytes on ascites-derived autologous tumor cell growth was studied in vitro using microplate assay. Nine (responders) of 12 patients showed complete disappearance or significant reduction of ascitic fluid. Ascites-derived lymphocytes slightly inhibited autologous tumor cell growth only in one case before OK-432 therapy. Lymphocytes collected from ascites after OK-432 injection significantly inhibited auto-tumor cell growth in all of 9 responders. In 3 non-responders, however, auto-tumor cell growth inhibition was found only in one case. Interestingly, lymphocytes from non-responders significantly inhibited the growth of tumor cells taken from responders. Conversely, lymphocytes from responders did not inhibit non-responder-derived tumor cell growth. These findings imply that auto-tumor killing by OK-432-induced lymphocytes may depend more on the condition of the tumor cells than on the condition of the lymphocytes, and that the measurement of auto-tumor killing activity by ascites-derived lymphocytes may be useful as an indicator in OK-432 therapy.

Abdominal Neoplasms↗

[A suppressive effect of PSK, a protein-bound polysaccharide preparation, on tumor growth: a new effect of PSK on cell motility].

We found that PSK has ambidextrous effects on cell motility. PSK enhances macrophage motility and inhibits tumor cell motility, when the capillary tube method was used in vitro. Macrophage motility was enhanced with increasing concentration of PSK. PSK inhibited tumor cell motility, i.e. Ehrlich tumor cells, EL-4 lymphoma cells and human leukemic cells, in dose dependent fashion. Macrophages and tumor cells were incubated with medium containing PSK for varying times at 37 degrees C and then washed with medium to eliminate PSK thoroughly. The motility of macrophages and tumor cells was enhanced and inhibited, respectively, with increasing pre-incubation time. When PSK-treated tumor cells were injected into the abdominal wall of C57BL/6 mice, PSK-treated tumor cells were less invasive than non-treated ones in mice. These phenomena are concern neither with the change of cellular viability nor that of cell proliferation.

Adjuvants, Immunologic↗

Malignant tumor and eosinophils. I. Prognostic significance in gastric cancer.

A prospective study with 647 gastric cancer was performed. Resected tumor specimens from 647 patients were examined with respect to eosinophil infiltration. Infiltration of the primary tumor by eosinophils was found to have a marked prognostic significance. Five years after the resection of tumor in the patients with gastric cancer, 29 of 51 patients (56.0%) who showed previously the infiltration of more than 100 eosinophils in tumor tissue were alive, while only 38.6% (61/158) of the patients with the infiltration of less than 100 eosinophils survived (P less than 0.05). Eosinophil infiltration in the resected tumor was detected in 157 patients (24%). The intensive degree of infiltration correlates well with a special pathologic type of cancer, poorly differentiated adenocarcinoma, the size of tumor mass and preoperative blood eosinophilia. The extract from tumors with the marked eosinophilic infiltration was highly chemotactic for eosinophils in vitro. The eosinophil chemotactic activity was found to be heat-labile and nondialyzable. It was therefore considered most likely that eosinophil infiltration in the tumor and blood eosinophilia observed in some patients with gastric cancer were caused by an eosinophil chemotactic factor of gastric cancer and the good indication of the prolonged survival of the patients.

Adenocarcinoma↗

Immunological studies on histiocytosis X. I. Special reference to the chemotactic defect and the HLA antigen.

We treated a family with three children with histiocytosis X (H-X). The chemotactic response of the neutrophils in these three patients was depressed and the chemotactic response of the neutrophils of the mother was also depressed compared to that of normal age-matched controls. To elucidate the genetic factors, we examined HLA antigens in five members of this family. All five members had Aw24, B7, Cw7, and DR1. Immunological and genetic studies in an additional 32 patients with H-X were performed. The chemotactic response of 35 patients with H-X (154.9 +/- 58.4/HPF) was significantly depressed in comparison with that of 35 age-matched healthy controls (613.3 +/- 116.7/HPF). In addition, the value of chemiluminescence of 20 of 35 patients (20.5 +/- 6.6 mV) was also significantly depressed in comparison with that of 20 normal controls (45.3 +/- 11.4 mV). The frequencies of Bw61 (54.4%) and Cw7 (45.4%) in 33 patients with H-X were significantly increased in comparison with those of 250 normal healthy controls (20.4 and 18.0%, respectively). Studies of immunoglobulin levels and complement titers of patients with H-X showed no consistent abnormalities. We proposed that defects of polymorphonuclear function may lead to an increased susceptibility to bacterial infections in patients with this disorder.

Adolescent↗

Plasma endotoxin levels and functions of peripheral granulocytes in surgical patients with respiratory distress syndrome.

Plasma endotoxin levels and granulocyte functions (chemiluminescence and chemotaxis) were determined in fifty-two patients with postoperative sepsis. Seventeen had concurrent respiratory distress syndrome (RDS group) and the remaining thirty-five were free of the syndrome (non-RDS group). The plasma endotoxin concentrations were higher in the RDS group than in the non-RDS group (p less than 0.001). All nine patients with particularly high levels (greater than 80 pg) belonged to the RDS group. We noted a positive correlation in chemiluminescence (p less than 0.001, r = 0.67) and a negative correlation in chemotactic activity (p less than 0.001, r = 0.69). To determine whether endotoxin alters normal granulocyte functions in vitro, healthy granulocytes were treated by the endotoxin (E. coli 0111:B4). There was an increase in chemiluminescence and a decrease in chemotactic activity, as observed in vivo. Furthermore, normal granulocytes chemiluminescence was increased by pretreatment of RDS plasma showing high endotoxin levels in vitro (n = 4, p less than 0.05). Thus, endotoxin in the plasma probably plays an important role in marked changes in peripheral granulocyte functions in patients with respiratory distress syndrome.

Adult↗