Biomedical subjects

M Torisu

Publications and source records attributed to M Torisu.

At least 19 recordsLinked to original sources

PubMed1995

A possible role of TGF-beta in the formation of malignant effusions.

The detailed mechanisms underlying the formation of malignant effusions are incompletely defined. In order to determine whether transforming growth factor-beta (TGF-beta) would contribute to the formation of malignant effusions, we investigated the effect of TGF-beta on the morphology, growth, and permeability of human mesothelial cells, which are thought to serve as a permeability barrier in the pleuroperitoneal cavities. Treatment of the mesothelial cells with a TGF-beta dose ranging from 0.1 to 10 ng/ml for 96 hr induced distinct morphologic changes in the cells. Each cell increased in size as did the volume of the intercellular spaces. TGF-beta also significantly inhibited the growth of mesothelial cells at a concentration ranging from 0.1 to 10 ng/ml. This growth inhibition was blocked completely by the addition of anti-TGF-beta antibody. Treatment of the mesothelial cells with 2.0 ng/ml TGF-beta significantly increased the permeability of a mesothelial cell monolayer as assessed by a FITC-albumin permeability assay. In our clinical analysis using 10 effusion samples obtained from patients with various types of carcinoma cells, considerable level of TGF-beta could be detected by ELISA, ranged from 0.90 to 8.75 ng/ml. Our data suggest that TGF-beta plays an important role in the formation of malignant effusions through structural and functional damage to the mesothelial cells. Malignant effusions may accumulate in the pleuroperitoneal cavity as a result of the mesothelial cell damage caused by this cytokine which is released from disseminated cancer cells.

Adult↗

PubMed1992

Characteristics of alveolar macrophages in experimental septic lung.

We investigated the pathogenesis of lung injury in sepsis (septic adult respiratory distress syndrome) by focusing on the functional changes of alveolar macrophages (AMs). Sepsis was induced in male WK rats by cecal ligation and puncture. Histological examination of the lungs from this experimental model revealed edematous change at 24 h after the surgery. The protein and endotoxin concentrations in the bronchoalveolar lavage fluid (BALF) increased with time after the surgery. The time course studies of AM function after surgery indicated that AMs from septic rats were activated by endotoxins. Specifically, this was suggested by the finding that AM adherence to and spreading on a plastic dish had increased. On stimulation, these AMs enhanced generation of superoxide anions and increased release of lysosomal enzymes, such as beta-glucuronidase. On the other hand, AMs in sepsis generated much smaller amounts of arachidonate lipoxygenase metabolites, such as leukotriene B4 (LTB4) and 12- and 5-hydroxyeicosatetraenoic acids (HETEs), on stimulation than did AMs from sham rats or untreated rats. However, the concentrations of immunoreactive LTC4 in the BALF of septic rats seemed to be higher than in untreated rats. It is suggested that the AMs of septic rats released lipoxygenase metabolites in alveoli and that these AMs could not be stimulated in vitro. These functional changes in the AMs of septic rats progressed along with the sepsis. These results implicate AMs in the development and progression of septic lung injury by releasing superoxide anions, beta-glucuronidase, and arachidonate metabolites. Furthermore, we speculate that reduced production of LTB4 by septic AMs may increase host susceptibility to severe pulmonary infection during septic ARDS.

Animals↗

PubMed1992

Suppression by interferon-gamma of tumor cell-induced increase in mesothelial permeability.

The effect of interferon-gamma (IFN-gamma) on the interaction between tumor cells and mesothelial cell layers was studied from the aspect of changes in mesothelial permeability. Mesothelial permeability was assessed as the percentage diffusion of radiolabeled albumin across the mesothelial cell sheets on Matrigel-coated filter cup assemblies. When lined gastric carcinoma cells (KATO-III) were seeded on the confluent mesothelial cell layers, the fine cobblestone appearance of the cell sheet was disrupted and mesothelial permeability significantly increased. The increase in permeability was suppressed by the addition of as little as 1 U/ml of IFN-gamma. The effect of IFN-gamma was observed when either the conditioned medium of tumor cells alone or the IFN-gamma-resistant tumor cells, K-562, was placed onto the mesothelium. The cobblestone appearance of the cell sheet was relatively well preserved in the presence of IFN-gamma. In contrast, IFN-alpha did not suppress tumor-induced mesothelial permeability. These results suggest that IFN-gamma has the potential to protect the human mesothelial cell layers against tumor cells.

Cell Communication↗

PubMed1992

The increase of low density subpopulations and CD10 (CALLA) negative neutrophils in severely infected patients.

We investigated the changes in polymorphonuclear leukocyte (PMN) subpopulations that accompany severe bacterial infection and examined their usefulness as a parameter for assessing the severity of infection. The Percoll density gradient was used to fractionate neutrophils into subpopulations of high density (1.09-1.10), intermediate density (1.08-1.09), and low density (1.07-1.08) with the majority of neutrophils from normal volunteers being of high density. By contrast, neutrophils from infected patients were of intermediate or low density, while those from severely infected patients showed a high percentage of the low density fraction with functional changes in lower chemotactic and beta-gulcuronidase activity. When each density subpopulation in the normal blood neutrophils was tested, low density PMNs had the lowest chemotaxis and minimal beta-glucuronidase activity. These results indicate that the increase in low density PMNs in patients with severe infection clearly reflects the functional impairment of PMNs. Flow cytometric analysis demonstrated that the neutrophils from severely infected patients had an decrease in CD10 expression. The percentage of CD10 positive PMNs correlated well with the severity of infection and with the clinical course of the patients. Thus, we conclude that PMN-density and CD10 expression change during severe bacterial infection, and that the measurement of PMN-subpopulations may be used to complement the clinical assessment of the severity of infections.

Bacterial Infections↗

PubMed1992

Pilonidal sinus on the neck.

A recurrent nuchal abscess was treated in a 21-year-old obese young man with a total excision of the lesion. In the histopathological findings, many similarities were found between this lesion and pilonidal sinus. We discuss the pathogenesis of this lesion, as well as our belief that this case was a rare example of pilonidal sinus on the neck.

Adult↗

PubMed1992

A case of linitis plastica of the rectum treated by pelvic exenteration after aggressive immunochemotherapy.

Multidisciplinary treatment was administered to a 32 year-old man with primary linitis plastica of the rectum, which was considered inoperable due to an extensive local spread at the first operation. Thirty KE of OK-432 was injected into the tumor per week (total 90-KE) and 5 KE of OK-432 was inoculated into the intracutaneous space per week (total 125 KE). Also methotrexete (MTX 50 mg) and 5-FU (500 mg) combined were given each week by intra-arterial infusion (total 20 courses). After this immuno-chemotherapy the CEA decreased from the pretreatment value of 12.7 ng/ml to 3.6 ng/ml and the tumor size was reduced. A total pelvic exenteration could then be performed almost curatively. As a result, this patient was able to return to the society with a better quality of life and has survived for 20 months since presentation.

Adult↗

PubMed1992

Evaluation of complement in patients with eosinophilic pneumonia.

Complement evaluation was performed in two patients with active eosinophilic pneumonia and in one in remission, to determine the role of complement activation in the pathogenesis of this disorder. All three had cough, dyspnea, malaise, and blood eosinophilia; two patients also had pyrexia. In all 3 cases the pulmonary eosinophilic infiltrates (radiographic findings) and symptoms responded rapidly to steroid administration. The two patients with active eosinophilic pneumonia showed elevated CR3 but reduced FcrR on the PMN before and during steroid administration. In contrast PMN from four patients with bronchial asthma exhibited slightly elevated expression of both CR3 and FcrR during their asthma attack. It is suggested that clinical symptoms disappear soon after the beginning of steroid but changes of complement receptors on PMN may last for longer periods. On the basis of the combined results, this study indicates that estimation of complement activation may provide a useful indicator for disease activity in patients with eosinophilic pneumonia of unknown etiology.

Adult↗

PubMed1991

Enhanced adherence activity of OK-432-induced peritoneal neutrophils to tumor cells correlates to their increased expression of CD11b/CD18.

We previously found that activated peritoneal neutrophils adhered to tumor cells and destroyed them in the cancer ascites of patients who had received intraperitoneal (ip) OK-432 injection therapy. Since tight adhesion to the tumor cell is essential for effective neutrophil-mediated tumor cell destruction, we investigated the mechanism of peritoneal neutrophil adhesion to tumor cells, using a microplate adhesion assay. An in vitro study demonstrated that the adherence activity of the peritoneal neutrophils of patients who received OK-432 injection therapy to tumor cells increased greatly compared to that of blood neutrophils. The expression of the adhesion molecules (CD11a,b,c/CD18) of peritoneal neutrophils, which was determined by an immunofluorescence study, was about four times as much in CD11b and twice as much in CD11c and CD18 compared to that in blood neutrophils. In vitro OK-432 stimulation of normal blood neutrophils increased neither the adhesion to PLC nor the CD11b expression. The enhanced adherence activity of peritoneal neutrophils to tumor cells was significantly inhibited by pretreatment of the neutrophils with anti-CD11b and anti-CD18 monoclonal antibodies (mAb), but not by pretreatment with anti CD11a or anti-CD11c mAb. These results indicated that the increased adhesiveness of OK-432-induced peritoneal neutrophils to tumor cells was due to the enhanced expression of CD11b/CD18. We concluded that CD11b/CD18 molecules on OK-432-induced peritoneal neutrophils play a crucial role in the neutrophil adherence activity against tumor cells, and these results are the first demonstration in the field of human neutrophil function.

Antigens, CD↗

PubMed1991

The anti Mac-1 monoclonal antibody inhibits neutrophil sequestration in lung and liver in a septic murine model.

We investigated the mechanism by which leukocytes adhere to the pulmonary and liver microvascular endothelium in a septic murine model. After C57BL/6 mice were intraperitoneally (ip) injected with lipopolysaccharide (LPS), a striking peripheral leukocytopenia occurred as neutrophils accumulated rapidly in the lung and liver. When the anti-Mac-1 monoclonal antibody (mAb) was administered intravenously (iv) 2 hr before the ip administrated LPS, leukocytopenia and neutrophil accumulation in the lung and liver were inhibited significantly at 3 hr after the LPS injection. An immunofluorescence study revealed that Mac-1 expression on leukocytes from LPS-injected mice were greatly increased when compared to that of controls. Additionally, an in vitro assay demonstrated that LPS-activated serum increased neutrophil Mac-1 expression and neutrophil adhesion to the endothelial monolayer and that these phenomena are inhibited by pretreatment of neutrophils with anti-Mac-1 mAb. These results indicate that a marked increase in Mac-1 antigen expression by leukocytes plays a crucial role in striking neutrophil attachment to the vascular endothelium and is likely to be the cause of neutrophil accumulation in the lung and liver during endotoxemia.

Animals↗

PubMed1991

Evidence that induction and regulation of lymphokine-activated killer (LAK) activity are mediated by changes in tumour-binding potential of lymphocytes after activation by interleukin-2 (IL-2).

The changes in the tumour-binding potential of human peripheral blood lymphocytes (PBL) after activation by interleukin-2 (IL-2) was investigated by directly counting the number of lymphocytes bound to lined hepatoma cell monolayers. A significant increase in the tumour-binding potential of PBL was found after activation by more than 100 U/ml of IL-2. Maximal tumour-binding potential was achieved at 1000 U/ml of activation, and an overdose of IL-2 activation slightly decreased this potential. These changes were almost exactly the same as the changes in anti-tumour cytotoxicity as measured by a 4-hr 51Cr-release assay. In addition, the kinetics of tumour binding by lymphokine-activated killer (LAK) cells was shown to be almost identical to that of tumour cell lysis. These results thus provide evidence that induction and regulation of LAK activity are mediated by changes in tumour-binding potential of lymphocytes after activation by IL-2.

Animals↗

PubMed1991

[Eighteen-year experience of cancer immunotherapies--evaluation of their therapeutic benefits and future].

The purpose of this study is to evaluate the therapeutic benefits of cancer immunotherapies and to predict the future of these therapies. The results of our clinical trials are as follows; (1) A group of gastric and colonic cancer patients at stages III-IV treated with BCG immunotherapy showed a significant prolongation of survival period (2) A significant prolongation of the disease-free period and the survival time were observed in the PSK-treated group in a randomized clinical trial on patients with curative surgical operation for stages III-IV colonic cancer. (3) We established clinically that intracavital administration of OK-432 is a useful therapy for patients with malignant pleuro-peritoneal effusions. We found that the reduction and disappearance of effusions were observed in more than 60% of patients with this therapy and they survived significantly longer. These results indicate that the immunotherapies may be effective to prolong survival period of advanced cancer patients with improvement of their quality of life. Furthermore, a series of our studies on the intracavital OK-432 injections for malignant ascites are useful to understand the reaction of host immune system against tumor cells.

Humans↗

PubMed1991

[Immunological assessment of the pathogenesis of septic-MOF: relationship between complement activation and changes in neutrophil functions].

We investigated the pathogenesis of septic-MOF through the relationship between changes in neutrophil functions and degree of complement activation. The patients' neutrophils exhibited enhanced adherence to HUVEC, suppressed chemotaxis toward C5a, enhanced production of oxygen radicals and lysosomal enzymes. These changes in neutrophil functions related to complement activation elicited via classical pathway. Moreover, the activated complement participated in tissue injuries due to the cytolytic action of the terminal complement complexes such as membrane attack complex (MAC). In conclusion, the combination of neutrophil and complement was strongly associated with the pathogenesis of the septic-MOF.

Bacterial Infections↗

PubMed1990

Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer.

To examine the clinical efficacy and the mechanism of action of polysaccharide K (PSK), a protein-bound polysaccharide extracted from a Basidiomycetes fungus, a randomized double-blind trial was performed by administering PSK to 56 patients and a placebo to another group of 55 patients after surgical operations on their colorectal cancers. The rate of patients in remission (or disease-free) was significantly higher in the PSK group than in the placebo group; the difference between both groups was statistically significant at P less than 0.05 by the log-rank test. The survival rate of patients was also significantly (P less than 0.05) higher in the PSK group than in the control group. The most significant laboratory finding was that polymorphonuclear leukocytes from PSK-treated patients showed remarkable enhancement in their activities, such as random and/or chemotactic locomotion, and phagocytic activity, when compared with those in the control group. In conclusion, PSK was useful as a maintenance therapy for patients after their curative surgical operations for colorectal cancer. The beneficial effects were probably due to the activation of leukocyte functions as one of the many biological-response-modifying (activities induced by PSK).

Administration, Oral↗

PubMed1990

Goitrous hypothyroidism with blocking or stimulating thyrotropin binding inhibitor immunoglobulins.

The significance of thyrotropin-binding inhibitor immunoglobulin (TBII) was evaluated in goitrous hypothyroidism associated with chronic thyroiditis (serum TSH greater than 10 mU/L, n = 148). TBII was measured by a RRA, and thyroid-stimulating antibody (TSab) and thyroid-stimulation-blocking antibody (TSBab) were determined using porcine thyroid cells. The prevalence of patients having TBII was 11% or 7.4% of 148 patients, which was not significantly different from that of 5% or 9.6% of 52 patients with atrophic thyroiditis. Although TBII was shown to be TSBab in 6, TSab was found in the other 5 patients despite hypothyroidism. There was little correlation between severity of hypothyroidism and TBII or TSBab activity. One patient continued to be latently hypothyroid despite apparently positive TSBab. Five other patients with TSBab and 2 patients with TSab suffered from overt, irreversible hypothyroidism, and 2 of the patients with TSBab continued to be hypothyroid even after the disappearance of TSBab. Biopsy of the thyroid gland performed in 4 patients revealed severely damaged thyroid follicles with mononuclear cell infiltration with or without fibrosis. Three of the patients with TSab had been taking excess iodine, and recovery of thyroid function was observed after iodine restriction. A perchlorate discharge test performed in two of these patients was positive, suggesting an iodide organification defect. These results indicate that, although TBII is not infrequently found in goitrous hypothyroidism, cellular or chemical damage of the thyroid gland plays an important role in the pathogenesis of thyroid hypofunction and TSBab may only have a precipitating role.

Adult↗

PubMed1990

New approach to management of malignant ascites with streptococcal preparation OK-432. III. OK-432 attracts natural killer cells through a chemotactic factor released from activated neutrophils.

When a streptococcal preparation, OK-432, was administered intraperitoneally to patients with malignant ascites, lymphocytes with cytotoxic activity against tumor cells increased in number in the peritoneal cavity after 5 to 7 days. To investigate the underlying mechanisms of such lymphocyte accumulation, lymphocyte chemotactic activity (LCA) in ascitic fluid was measured by a modification of the Boyden method. High LCA was found on the third and fourth days after the OK-432 injection. This LCA was generated in the cell-free supernatant of the patients' abdominal neutrophils that accumulated in the peritoneal cavity 24 hours after the injection of OK-432. A similar LCA was also found when normal peripheral neutrophils were incubated with OK-432. Incubation of normal neutrophils without OK-432 failed to generate LCA, however, and OK-432 alone had no LCA. We tentatively named this factor "neutrophil-derived lymphocyte chemotactic factor" (NDLCF). The NDLCF was heat stable and nondializable, and its molecular weight was approximately 45,000 daltons. It attracted mainly natural killer cells by immunoperoxidase assay of migrated lymphocytes in the chemotactic membrane. These characteristics were distinct from C5a, interleukin-1, and interleukin-2. The results suggest that the newly found NDLCF may be responsible for the infiltration of cytotoxic lymphocytes, especially natural killer cells in the peritoneal cavity in patients with malignant ascites when treated by intraperitoneal injections of OK-432.

Animals↗

PubMed1989

Gas-containing pyogenic liver abscess--a case report and review of the literature.

The incidence of gas-containing pyogenic liver abscess is exceedingly rare. We report herein, a case of a 36-year-old Japanese woman with a gas-containing pyogenic liver abscess associated with diabetes mellitus and cholelithiasis. An abdominal plain X-ray film, which showed a fine air-fluid level in the liver at an up-right position, enabled us to easily diagnosed a gas-containing liver abscess. Echo-guide percutaneous drainage revealed the organism to be Escherichia coli, however, although this treatment has recently been employed often in the treatment of pyogenic liver abscesses, especially single abscesses, it did not prove effective in this case. We finally cured the gas-containing pyogenic liver abscess by operative drainage.

Adult↗

PubMed1989

A new surgical approach for treating infected epidermoid cysts using delayed primary closure.

A new surgical approach for treating infected epidermoid cysts was designed. This technique involves the lesion being incised and drained on the first day, 5-7 days after which it is removed together with the cyst wall excised parallel to Langer's tension lines. The wound is then closed by delayed primary closure. We employed this method in the treatment of 12 patients and observed the average time required for recovery (n = 12) was 18.6 +/- 2.5 days (mean +/- SD) and the number of days spent at the outpatient clinic, 10.2 +/- 2.6. There has been no recurrence or secondary infections in any of the patients to date.

Abscess↗

PubMed1989

Migration of putative progenitor T cells in response to thymus-derived chemotactic factors.

Progenitor T cells reach the thymus through the circulation from hematopoietic organs and then migrate toward the site of differentiation in the thymus. The mechanism that regulates such intrathymic migration is not well understood. In order to clarify this mechanism, in vitro chemotactic activity for murine thymocytes was assayed in the extracts and culture supernatants of thymic tissue elements. A potent thymocyte chemotactic activity was found in the extract and culture supernatant from Ig-, Ia- thymic stromal cells. Peanut agglutinin-positive (PNA+1), Thy 1+, TL-, Lyt 1+2-, L3T4- thymocytes, Ig-, Thy 1- bone marrow cells, and mononuclear cells of spleen and peripheral blood, but neither B cells nor lymph node cells, were chemotactically attracted by the factor(s). The chemotactic activity was found in none of the following materials tested: the extract and culture supernatant of thymocytes, culture supernatant of lymph node stromal cells, normal mouse serum, and zymosan-activated serum. The chemotactic activity was found in three molecular fractions by gel chromatography. The activity in all three fractions was destroyed by trypsin digestion or by heating at 56 degrees C for 30 min. These results suggest that Ig-, Ia- thymic stromal cells but not thymocytes secrete a chemotactic factor(s) for progenitor T cells with three molecular species. The factor is considered to play an important role in the migration of intrathymic progenitor T cells into the site of differentiation.

Animals↗