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K Inada

Publications and source records attributed to K Inada.

At least 145 records · Page 8Linked to original sources
PubMed1993

Increased expression of membrane-associated phospholipase A2 shows malignant potential of human breast cancer cells.

BACKGROUND: Recently, the authors reported that membrane-associated phospholipase A2 (M-PLA2) was one of the acute phase reactants and increased in serum of patients with various malignant tumors. METHODS: M-PLA2 concentrations in tissue specimens from 78 breast cancers, 16 benign breast tumors, and 10 normal breast tissues were determined by a specific radioimmunoassay recently developed. Immunohistochemical staining was performed on all specimens by the avidin-biotin-peroxidase method. RESULTS: Tissue levels of M-PLA2 concentration were significantly higher in breast cancer than in benign breast tumor or normal breast tissue (P < 0.01). Correlation analyses between the tissue concentration of M-PLA2 and clinicopathologic factors showed that tissue M-PLA2 levels were significantly higher in patients with skin or muscle invasion, vessel involvement, and distant metastasis than in those without. In addition, this enzyme concentration was significantly greater in scirrhous carcinoma than in papillotubular or solid-tubular carcinoma. No association was found between M-PLA2 concentration and steroid hormone receptor status. Immunohistochemically, M-PLA2 was preferentially stained in the invading zone of breast cancer tissues, especially in scirrhous carcinoma. Patients with breast cancer with low levels of M-PLA2 showed significantly longer overall survival and disease-free survival compared with those with high levels of this enzyme at the cutoff point of 50 ng/100 mg protein. The combination of estrogen receptor status with M-PLA2 concentration could be a powerful prognostic factor in predicting such survival rates. CONCLUSIONS: M-PLA2 is closely related to the malignant potential of breast cancers, and the M-PLA2 contents in breast cancer tissues could be a new valuable prognostic factor, other than the hormone receptor, in delineating the status of human breast cancer.

Breast↗
PubMed1993

Interleukin 6 stimulates the production of immunoreactive endothelin 1 in human breast cancer cells.

To investigate the potential regulation of endothelin 1 production in human breast cancer cells, we measured the release of immunoreactive endothelin 1 (ir-ET-1) from the MCF-7 and ZR-75-1 breast cancer cell lines in response to various agents including estrogen and tamoxifen as well as several cytokines. ir-ET-1 was detected in conditioned medium of MCF-7 cells and ZR-75-1 cells by specific radioimmunoassay. Among the agents tested, estrogen, tamoxifen, tumor necrosis factor, gamma-interferon, interleukin (IL) 1, and transforming growth factor beta had no effect on ir-ET-1 secretion by these breast cancer cells. However, IL-6 (20 ng/ml) treatment of MCF-7 cells and ZR-75-1 cells caused maximal increases in the amount of ir-ET-1 secreted into the culture medium to 206 and 314% of basal values after 6 h, respectively. This effect of IL-6 on ir-ET-1 secretion was inhibited by actinomycin D and cycloheximide, indicating that IL-6 stimulates de novo synthesis of ir-ET-1 at a transcriptional level. Reverse-phase high performance liquid chromatography coupled with radioimmunoassay in the conditioned medium from IL-6-treated cells revealed one major ir-ET-1 component corresponding to human standard ET-1. The present study demonstrates the potential for IL-6 to stimulate ir-ET-1 production in human breast cancer cells, which may participate in the process of acute phase reactant-like expression of this peptide and/or in the process of IL-6 enhanced breast cancer cell motility, the latter being recently clarified.

Breast Neoplasms↗
PubMed1993

Both CD45RA+ and CD45RA- subpopulations of CD8+ T cells contain cells with high levels of lymphocyte function-associated antigen-1 expression, a phenotype of primed T cells.

Expression of CD45 isoforms and some adhesion molecules on T cells change during T cell activation. In CD4+ T cells, it has been reported that CD45RA is lost and CD45RO is up-regulated when CD4+ T cells are stimulated. This change seemed to be irreversible and thus CD45RA may serve as a marker for virgin T cells and CD45R0 as a marker for memory T cells in CD4+ T cells. In CD8+ T cells, however, the expression of CD45 isoform has been less well understood. We have previously reported the switching of CD45 isoform expression may be reversible and CD8+CD45RA+ T cells may contain preactivated T cells. We present further evidence to support this notion by investigating the expression of lymphocyte function-associated Ag (LFA-1) in relation to CD45 isoform expression in various T cell populations in the human. In the thymus and umbilical cord blood, more than 97% of both CD4+ and CD8+ single positive T cells expressed LFA-1 at a low level. In CD4+ peripheral blood T cells, a high level of LFA-1 expression was found only in the CD45RA- population: 98% of CD45RA+ cells were LFA-1low. In CD8+ peripheral blood T cells, in contrast, a distinct population of LFA-1high cells was found in CD45RA+ subset, comprising about 45% of this subset in a 32-yr-old donor. In 7 days after stimulation with PHA, all CD4+ and CD8+ T cells, irrespective of their CD45 isoform expression, were LFA-1high. The proportion of CD45RA+ cells decreased in CD4+ but slightly increased in CD8+ T cells after the stimulation. These results support the notion that CD45RA and CD45R0 mark virgin and memory T cells respectively in the CD4+ T cells, and that CD8+CD45RA- T cells are primed. However, the validity of CD45RA as a marker of virgin cells in CD8+ T cells is seriously questioned.

Adult↗
PubMed1993

Age-related accumulation of LFA-1high cells in a CD8+CD45RAhigh T cell population.

The differential expression of CD45 isoforms has been suggested as a marker for stages of post-thymic T cell development, that is, CD45RA+CD45R0-T cells and CD45RA-CD45R0+ T cells are supposed to be virgin and memory cells respectively. Recently, several adhesion molecules have been shown to be up-regulated on the cell surface of memory T cells, and have been suggested to serve as a memory marker. In this study, we investigated the levels of LFA-1 expression on T cells in various subpopulations defined by CD45 isoform expression in donors of various ages. In CD4+ T cells, the proportion of LFA-1high cells among CD45RAhighCD45R0- T cells remained low in all age groups and did not show significant accumulation with age. CD4+CD45RA-CD45R0high T cells expressed LFA-1 at a higher level than CD4+CD45RAhighCD45R0- T cells. Thus, the currently prevailing view that CD45RA and CD45R0 can be markers for virgin and primed cells was consistent with LFA-1 expression in CD4+ T cell population. In CD8+ T cells, however, CD45RAhighCD45R0- T cells consisted of two distinct subpopulations, LFA-1low and LFA-1high cells, whereas CD45RA-CD45R0high T cells were almost exclusively LFA-1high. When CD29 expression was examined in place of LFA-1 expression, similar results were obtained; CD45RAhigh CD45R0- T cells consisted of two distinct subpopulations, CD29-to low and CD29high cells, while CD45RA-CD45R0high T cells were mostly CD29high. The proportion of LFA-1high cells in the CD8+CD45RAhigh T cell subpopulation increased significantly as a function of age (r = 0.9, p < 0.001). It ranged from 8% in a 14-year-old donor to 94% in a 79-year-old donor. Furthermore, the proportion of CD8+CD45RAhighLFA-1high cells in the CD8+ T cell population increased significantly as a function of age (r = 0.85, p < 0.001). On the other hand the proportion of LFA-1high cells in CD8+CD45RA- T cell subpopulation exceeded 90% in most donors irrespective of age. These results indicate that the CD8+CD45RAhighCD45R0- T cell subpopulation contains a considerable number of LFA-1high cells and CD29high cells, phenotypically similar to previously activated cells. Thus, in terms of LFA-1 and CD29 expressions, the simple scheme that CD45RA is a marker of virgin cells is not applicable to the CD8+ T cell population.

Adolescent↗
PubMed1993

Plasma tumour necrosis factor-alpha (TNF-alpha) levels in patients with burns.

Levels of plasma tumour necrosis factor-alpha (TNF-alpha) were determined consecutively in 42 patients with burns > 20 per cent of the total body surface area using an enzyme-linked immunosorbent assay. In the early period after injury (including the period of burn shock), 24 patients had detectable TNF-alpha levels in their plasma. However, the plasma TNF-alpha levels at the time of admission were very low and did not correlate with the extent of the burn or the prognosis. In contrast, the maximum plasma TNF-alpha level over the whole clinical course was significantly correlated with the area of the burn and the prognosis. No correlation was found between the plasma TNF-alpha and plasma endotoxin levels. TNF-alpha may be produced locally in infected burns and monitoring of plasma TNF-alpha levels may be a useful prognostic indicator for burns patients.

Adult↗
PubMed1993

Differential biological significance of tissue-type and urokinase-type plasminogen activator in human breast cancer.

Plasminogen activator (PA) is a serine protease existing in two forms known as tissue-type (t-PA) and urokinase-type (u-PA). To examine whether PA is related to the postoperative clinical course of human breast cancer, total PA activity, t-PA activity, u-PA activity, and immunoreactive t-PA were determined in tissue extracts from 144 breast cancer specimens. The patients were initially divided into four groups according to the postoperative clinical course: Group I (83 patients who are disease-free), Group II (20 patients whose first metastases were found only in bone), Group III (19 patients whose first metastases were found in both bone and lung), and Group IV (22 patients whose first metastases were found only in lung). Total PA activity was significantly lower in Groups, II, III and IV than in Group I. Both t-PA activity and t-PA antigen levels were also significantly lower in Groups II, III and IV than in Group I, while no significant difference was found in u-PA activity among these groups, indicating that low activity of total PA in Groups II, III and IV was due to a decrease in t-PA but not in u-PA. In the multivariate analyses, t-PA activity was found to be an independent prognostic factor for relapse-free survival. When four groups of patients were further analysed in terms of nodal status, both t-PA activity and antigen levels were markedly decreased in the node-negative Group II compared with the node-negative Groups III and IV or with the node-positive Groups II, III and IV. Of additional interest, u-PA activity was significantly higher in node-positive patients than in node-negative patients with any group. The clinico-pathologic analyses of the patients in this series showed that node involvement and lymphatic invasion were more frequently positive in Groups III and IV than in Groups I and II. When 144 breast cancers were categorised in terms of combinations of oestrogen receptor (ER) and progesterone receptor (PgR) status, breast cancers which were positive for both receptors were found to contain the highest t-PA activity and antigen. This study provides provocative evidence suggesting a possible differential significance of t-PA and u-PA expression in human breast cancer.

Bone Neoplasms↗
PubMed1993

Breast cancer prognosis is poor when total plasminogen activator activity is low.

Plasminogen activator (PA) is a serine protease which exists in two forms: tissue-type (t-PA) and urokinase-type (u-PA). The total PA activity was measured in tumour extracts of 235 breast cancer patients who were followed for a median of 8.5 years after surgery. Patients were initially divided into three groups with low (< 60 units mg-1 protein), intermediate (60-300 unit mg-1 protein), or high (> 300 unit mg-1 protein) total PA activity in tumour extracts. The PA activity was not significantly associated with the recognised prognostic factors of age, menstrual status, tumour size, lymph node involvement, histologic type, grade of anaplasia, and/or vessel involvement. A significant association was found between total PA activity and the oestrogen receptor (ER) or progesterone receptor (PgR) status. Among receptor-positive tumours, a significantly greater proportion of patients had high PA activity in their tumour extracts. Breast cancer patients with low total PA activity had a significantly shorter disease-free and overall survival rate when compared to those with intermediate or high PA activity. In univariate and multivariate analyses, total PA activity (< 60 unit mg-1 vs > or = 60 unit mg-1 protein) was found to be a significant prognostic factor for disease-free and overall survival of about the same import as lymph node involvement. Furthermore, the combination of total PA activity and nodal status could be even more precise in predicting survival times and probabilities in individual patients. This retrospective study demonstrates the total PA activity is a valuable prognostic factor in determining prognosis in human breast cancer.

Breast Neoplasms↗
PubMed1993

Usefulness of a new perchloric acid treatment method to measure endotoxin in cerebrospinal fluid by the limulus test.

The modernized limulus lysate assay on cerebrospinal fluid pretreated by the new perchloric acid (PCA) treatment was evaluated in one patient with Escherichia coli meningitis and four non-meningitis patients. The endotoxin (ET) concentration was much higher by the new PCA treatment than by the ordinary dilution method in the exacerbation phase of E. coli meningitis. The recovery rate of added ET also demonstrated the superiority of the new PCA treatment.

Colorimetry↗
PubMed1993

[Inhibitory effect of mouse antiendotoxin monoclonal antibody (E5) on hypotension induced by endotoxin and TNF-alpha].

Mouse anti-endotoxin monoclonal antibody (E5) is now under clinical trial (Phase II) in Japan by assessing clinical findings and plasma endotoxin levels. We attempted to evaluate an inhibitory effect of E5 on hypotension induced by endotoxin and TNF-alpha. Systolic blood pressure was measured with a programmable sphygmomanometer using the tail-cuff method. The mixture of endotoxin (E. coli O111:B4, Sigma, 2 micrograms/mouse) and recombinant mouse TNF-alpha (Genzyme, 8000 units) were injected into mice (ddY, 6-8-weeks-olds), and the change of blood pressure was observed for 3 hrs. The mixture significantly decreased the blood pressure to about 70% of the control. E5 (20 micrograms/mouse), which was injected 10 min before, significantly abrogated the effect of endotoxin and TNF-alpha. The hypotension induced by the mixture was definitely inhibited by the injection of E5 (50, 100 micrograms/mouse), injected 10 min later, or the injection of E5 (100 micrograms/mouse) 30 min later. We previously found that E5 prevents the lethality induced by a concomitant injection of endotoxin, TNF-alpha and IL-2. These results suggest that E5 effective for inhibition of endotoxin activity in vivo.

Animals↗
PubMed1993

Immunohistochemical expression of PIT-1 protein in pituitary glands of human GRF transgenic mice: its relationship with hormonal expressions.

It has been suggested that pit-1 protein may play a role in the differentiation of the anterior pituitary cells. The present immunohistochemical studies were designed to elucidate the relationship between functional differentiation of pituitary adenoma and expression of pit-1 protein in human (h) GRF transgenic mice. Pituitaries from a 10 month old and a 6 month old transgenic mice were fixed in 4% paraformaldehyde and embedded in paraffin. The indirect immunoperoxidase method was performed using antibodies against hGRF, GH, PRL, ACTH, alpha subunit (SU), FSH beta SU, LH beta SU, TSH beta SU, and pit-1 protein. Immunohistochemical double staining was performed at light and electron microscopic levels. The pituitary glands of hGRF transgenic mice (both 10 month and 6 month old) demonstrated diffuse hyperplasia of GH positive cells with coexpression of hGRF within the same cells. There were also scattered cells which were positive for other hormones and hormone subunits in the hyperplastic pituitary. Three discrete nodules were found in the pituitary gland of a 10 month old hGRF transgenic mouse and were identified as adenomas. These adenomas were composed of enlarged round cells which were positive only for GH, hGRF, PRL and TSH beta SU. Pit-1 protein was intensely expressed in the nuclei of the adenoma cells. These results suggest the existence of an autocrine mechanism by hGRF in the formation of somato-lacto-thyrotroph adenoma via constitutive pit-1 expression.

Adenoma↗
PubMed1993

The inhibitory actions of protease inhibitors on the production of polymorphonuclear leukocyte elastase and interleukin 8.

The inhibitory actions of Ulinastatin, which is a protease inhibitor, on the production of polymorphonuclear leukocyte elastase (PMN-elastase) and interleukin 8 (IL-8) in vascular endothelial cells were evaluated. Our findings suggest that IL-8 plays a role in the production of PMN-elastase. Ulinastatin inhibited the lipopolysaccharide (LPS)-stimulated activity of polymorphonuclear leukocytes (PMN) and the production of IL-8 in vascular endothelial cells. Ulinastatin also inhibited the LPS-stimulated production of PMN-elastase in PMN.

Dose-Response Relationship, Drug↗
PubMed1993

[Variation of the diploid pattern in tissues used as normal controls of solid tumors: advantages and disadvantages of flow cytometric analysis of paraffin-embedded tissues].

The aim of the present work was to study the factors that influence the variation of diploid patterns in 75 areas of histologically normal gastric tissue, located in surgically resected stomachs due to early gastric cancer. Each sample was used as a diploid reference of its respective tumoral area. Fifty five samples were embedded in formalin and 20 corresponded to fresh tissue. It was found that in the older tissues, the cellular debris increased, the localization channel of the peaks shifted to the left (lower than channel 60) and the peak shape was deformed, with an increase in the variation coefficient (around 6) and an elevation and lengthening of phase S. When fresh tissue was used, the first peak was localized around channel 60-70, with a significant reduction of cellular debris, a lower variation coefficient amplitude (2-5) and a phase S adhered to the basal line. Aiming to observe the influence of paraffin embedding over time, 21 tissue samples originally assayed as fresh tissues, were reanalyzed one year later. The same alterations initially observed in old tissues were again noticed. According to these results, it is necessary to select adequate controls for flow cytometric analysis to obtain an adequate histogram interpretation, and specially to calculate the ADN index.

Adult↗
PubMed1993

[A case of angiosarcoma presenting as ill-defined opacities on chest roentgenogram and hemothorax].

A 74-year old male was referred to the Tokai University Hospital for evaluation of abnormal opacities on a chest roentgenogram. Laboratory tests demonstrated leukocytosis, elevated ESR and CRP, elevated LDH, and hypoxemia. The chest roentgenogram demonstrated several ill-defined nodular infiltrates on the bilateral upper lung fields. In addition, a CT scan revealed bilateral pleural effusion which was found bloody on diagnostic thoracocentesis. Administration of antibiotics failed to improve lung infiltration or laboratory data. The patient died of respiratory failure on the 23rd hospital day. At autopsy, multiple ill-defined nodules, which were associated with alveolar hemorrhage, were scattered in the lungs bilaterally. Both hematoxylin-eosin and silver staining showed atypical cells of a vasoformative nature. Factor VIII related-antigen in the tumor cells was confirmed by the peroxidase-antiperoxidase method. These findings were consistent with angiosarcoma. The tumor foci were demonstrated in the lungs, pleura, kidneys, bone marrow, adrenal glands, and the gastrointestinal tract. The primary site of angiosarcoma, however, was not identified. Angiosarcoma, either primary or metastatic to the lungs, should be included in the differential diagnosis of multiple ill-defined nodular opacities associated with hemothorax.

Aged↗
PubMed1993

[Human cultured retinal pigment epithelial cells produce interleukin-6].

Production of interleukin 6 (IL-6) from cultured human retinal pigment epithelial cells (RPE) was demonstrated using an enzyme-linked immunosorbent assay. Production of IL-6 occurred without any stimulation and significantly increased approximately 2-5 times by lipopolysaccharide (LPS) or interleukin 1 alpha stimulation. Hydrocortisone reduced the production of the LPS-stimulated IL-6 to a half level. Both gel filtration and western blotting analysis indicated the molecular weight of IL-6 as 30,000-35,000. IL-6 produced in the RPE may play a role in amplifying ocular immune and inflammatory responses.

Cells, Cultured↗
PubMed1993

[A case of lung adenocarcinoma with high CT number, high calcium concentration but no calcification].

A 36-year-old woman with lung adenocarcinoma is reported. Chest X-ray film showed a high CT number, but no calcified lesion was detected. Histologic examination demonstrated no bone formation, calcification, or psammoma bodies. Calcium staining with Kossa method was negative. An elementary analysis with penetrating type electron microscopy and energy dispersion type analyzer showed high calcium concentration in the tumor. It was thought that the tumor showed a high CT number because of masked soluble calcium.

Adenocarcinoma↗
PubMed1992

Abundant expression of immunoreactive endothelin 1 in mammary phyllodes tumor: possible paracrine role of endothelin 1 in the growth of stromal cells in phyllodes tumor.

Immunoreactive endothelin 1 (irET-1) concentrations were measured in extracts prepared from 4 phyllodes tumors and 14 fibroadenomas. irET-1 was detectable in all tissue extracts by specific radioimmunoassay, and the mean concentration of irET-1 was 18-fold and 27-fold higher in tissue extracts from phyllodes tumors than in those from intracanalicular fibroadenomas and pericanalicular fibroadenomas, respectively. Reverse-phase high-performance liquid chromatography coupled with radioimmunoassay in the extracts from phyllodes tumors revealed one major irET-1 component corresponding to human standard ET-1. Furthermore, immunocytochemical staining for ET-1 revealed that numerous ET-1-immunoreactive cells were seen in the epithelial cells but not in the stromal cells, suggesting that ET-1 is synthesized by the epithelial component of phyllodes tumors. A possible paracrine role of ET-1 in the growth of this rare tumor which is characterized by its prominent stromal cellularity is discussed.

Adenofibroma↗
PubMed1992

CD45 isoform expression during T cell development in the thymus.

Various isoforms of leukocyte common antigen, or CD45, are expressed differentially on T cells at different stages of development and activation. We report studies on CD45 isoform expression on various subsets of human T cells using two- and three-color flow cytometry and cell depletion. Bone marrow cells that were depleted of CD3+ and HLA-DR+ cells were CD45RA-RO-. The earliest CD3-CD4-CD8-CD19- thymocytes were CD45RO- with 20%-30% CD45RA+ cells. The most prominent population of CD4+CD8+ double-positive thymocytes were CD45RA-RO+. Even the CD4+CD8+ blasts were greater than 90% CD45RO+. About 80% of single-positive thymocytes (CD4+CD8- or CD4-CD8+) were also CD45RO+. Only 4.3% of CD4+ and 18% of CD8+ single-positive thymocytes were CD45RA+. In contrast, cord blood T cells which represent the stage that immediately follows single-positive thymocytes, contained 90% CD45RA+ cells. Thus, in terms of CD45 isoform expression, single-positive thymocytes are more like double-positive cells than cord blood T cells. These results suggest the following sequence of CD45 isoform switching during T cell development: CD45RA-RO- or RA+RO- (double-negative thymocytes)----RA-RO+ (double-positive and most single-positive thymocytes)----RA+RO- (cord blood T cells), the last switch from CD45RO to CD45RA occurring as a final step of maturation in the thymus.

Antigens, CD↗