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Biomedical subjects

N Shijubo

Publications and source records attributed to N Shijubo.

At least 73 records · Page 4Linked to original sources

Lung adenocarcinoma with type II pneumocyte characteristics.

We report a case of primary lung adenocarcinoma with type II pneumocyte characteristics. Electron microscopic examination demonstrated that the tumour cells had well-developed microvilli and cytoplasmic lamellar inclusion bodies. These ultrastructural features are similar to those seen in type II pneumocytes of normal lung tissue. Western blot analysis, using monoclonal antibody against human surfactant protein A (SP-A), clearly demonstrated that the tumour cells expressed human SP-A, which is a major pulmonary surfactant protein produced by type II pneumocytes. These observations suggest that the tumour was derived from a type II pneumocyte.

Adenocarcinoma↗

Pulmonary surfactant protein A in pleural effusions.

Pulmonary surfactant protein A (SP-A) is known to be a major phospholipid-associated glycoprotein in pulmonary surfactant, which is specific to the lung. Immunohistochemically, expression of SP-A in tumor tissues is found in approximately 50% of patients with lung adenocarcinoma but not in the other histologic types of lung cancer of metastatic lung tumors. In this study, the SP-A content of pleural effusions was determined using an enzyme-linked immunosorbent assay. These results showed that approximately 40% of patients with lung adenocarcinomas (27 of 67) had high levels of SP-A (greater than 500 ng/ml) in their pleural effusions. By contrast, patients with other histologic types of lung cancers, adenocarcinomas of different primary sites, and tuberculosis had low levels of SP-A in their pleural effusions. The determination of SP-A in malignant effusions will contribute to distinguishing primary lung adenocarcinoma from adenocarcinomas of miscellaneous origin.

Adenocarcinoma↗

Circulating intercellular adhesion molecule-1 (ICAM-1) antigen in sera of patients with idiopathic pulmonary fibrosis.

Intercellular adhesion molecule-1 (ICAM-1), a member of immunoglobulin supergene family with a five-domain structure, is known to play an important role in inflammatory diseases. An ELISA was developed using two MoAbs against human ICAM-1 in order to detect the soluble shedding ICAM-1 antigen in sera. We measured levels of circulating ICAM-1 antigen in sera of patients with idiopathic pulmonary fibrosis (IPF), pulmonary sarcoidosis, hypersensitive pneumonitis, bacterial and mycoplasmal pneumonia, and inflammatory diseases of other organs. The results clearly demonstrated that IPF had significantly high levels of circulating ICAM-1 in sera as compared with other disorders or normal controls. Moreover, immunohistochemical analysis with MoAb against human ICAM-1 disclosed that in IPF, the expression of ICAM-1 was intensively enhanced on alveolar epithelial cells. These results suggest that ICAM-1 may contribute to the pathogenesis of IPF.

Adult↗

Squamous cell carcinoma of unknown origin in middle mediastinum.

We report a rare case of squamous cell carcinoma located in the middle mediastinum as a solitary mass. Histologically, lymphatic tissues remained together with nests of squamous cell carcinoma which were occupying the greater part of the mass. Examinations of the whole body failed to detect a primary site of the squamous cell carcinoma. It is considered that the carcinoma cells reflect metastasis from a primary-unknown carcinoma (most likely TO lung squamous cell carcinoma) or that they originated from benign epithelial inclusions in a mediastinal lymph node.

Carcinoma, Squamous Cell↗

Granulocyte colony-stimulating factor-producing large cell undifferentiated carcinoma of the lung.

We report a case of granulocyte colony-stimulating factor (G-CSF) producing lung cancer. A 38-year-old Japanese woman had a large cell undifferentiated carcinoma of the left lung with severe granulocytosis without any evidence of infection. A specimen was taken from a metastatic cervical lymph node and a tumor cell line was established. The culture supernatant of the line as well as patient's serum exhibited a high level of G-CSF by sandwich enzyme immunoassay. Immunohistochemical analysis demonstrated that tumor cells from transplanted nude mice were stained granularly in the cytoplasma by anti-human G-CSF monoclonal antibody, 4A6.

Adult↗

[Granulocyte colony-stimulating factor producing lung large cell carcinoma with sarcomatous transformation].

We report a case of granulocyte colony-stimulating factor (G-CSF) producing lung large cell carcinoma with sarcomatous transformation. A 57-year-old man was admitted for evaluation of an abnormal shadow near the right pulmonary hilus on chest X-ray film. Brush cytology specimen from right B6 disclosed large cell carcinoma. His clinical stage was already IIIB (T3N3M0) on admission, so we immediately administered chemotherapy and radiation therapy. However, the patient's condition gradually deteriorated and he died of respiratory failure. Although there was no evidence of infection throughout his clinical course, his peripheral white blood cell count gradually increased and reached 47,000/mm3 (neutrophils 96%) before death. Histological study of the autopsy specimen revealed that the primary tumor was composed of two different elements (large cell carcinoma and spindle cell sarcomatoid element). The spindle cell sarcomatoid element appeared to have arisen from sarcomatous transformation of carcinoma cells, because the transition margin of the carcinoma to the sarcomatoid element was smooth, and special and immunohistochemical staining of both elements showed the same properties. Moreover, immunohistochemical study with monoclonal antibody to human G-CSF, 4A6 clearly demonstrated granular staining of G-CSF in the cytoplasm of tumor cells.

Carcinoma↗

[A case of systemic arterial supply to normal lung without sequestrated lung].

A 19-year-old man was admitted to our hospital because of bloody sputum. His chest radiograph showed funicular shadows adjacent to the descending aorta in the left lower lobe and absence of vascular structures in the lower portion of the left hilum. His chest CT showed increased vascularity and slightly increased parenchymal density in the left basal segments. No cystic lesions were observed on CT. Angiographic examinations revealed that the left basal segments were supplied by an aberrant artery arising from the thoracic aorta, instead of the pulmonary artery. Left lower lobectomy was performed. Gross findings at surgery and histological examination confirmed the diagnosis of systemic arterial supply to normal lung without sequestrated lung. The main histological findings of the specimen were hemorrhage in alveolar spaces and dilatation of vessels. These findings seemed to correspond to the CT findings. We consider that CT is useful for the diagnosis of this disease.

Adult↗

[A case of chronic interstitial pneumonia with benign monoclonal gammopathy (IgM-k) and thrombocytopenia].

A 53-year-old woman was admitted on 13th October 1988 with symptoms of dry cough and shortness of breath persisting for 1 year. On physical examination, fine crackles were audible over her back. Chest X-ray showed bilateral reticulonodular shadows and collapse of the bilateral lower lobes. Chest CT showed patchy areas of increased density distributed predominantly in the subpleural zone. Laboratory data on admission showed thrombocytopenia, hypergammopathy (IgG, 2044 mg/dl; IgA, 286 mg/dl; IgM, 1645 mg/dl), and positive ANF. Further examinations demonstrated that anti-platelet and anti-centromere antibodies were positive in the serum, and the titer of PA-IgG was high (56 ng/10(7) platelets). Histopathological examination of the open lung biopsy demonstrated honeycombing and thickening of the alveolar walls, with slight infiltration of chronic inflammatory cells. These histopathological findings were comparable with usual interstitial pneumonia. We report a very rare case of chronic interstitial pneumonia complicated by benign monoclonal gammopathy and thrombocytopenia. Although it remains unclear, these abnormalities may have been caused by immunological mechanisms.

Autoantibodies↗

[A case of pulmonary sarcoidosis with B lymphocytosis in peripheral blood].

A 24-year-old man was admitted on October 14, 1988, with bilateral cotton-like shadows on chest X-ray film. Chest CT demonstrated multiple nodular shadows in bilateral lung fields. Laboratory data on admission showed peripheral blood lymphocytosis and slight decrease of serum IgG and IgA. ACE was within normal limits, and BALF findings showed no increase of lymphocytes. Surface marker analysis of peripheral blood lymphocytes showed an increase of B lymphocytes of antibody independent stage (B1, B4, J5, OKB7, sIgM, and sIgD positive cells were increased). Southern blot analysis of peripheral blood showed no rearrangement of immunoglobulin chains (H chain and L chain). In order to differentiate sarcoidosis from lymphoproliferative disorder, open lung biopsy was performed. Pathologic study revealed multiple epithelial granulomas without caseation. Immunohistochemical study demonstrated no accumulation of B cells of the lung. This patient was pathologically diagnosed as having pulmonary sarcoidosis. The abnormal chest shadows gradually improved without therapy; however, B cell lymphocytosis and slight decrease of serum IgG and IgA persisted. In general, lymphocytopenia of peripheral blood is usual in sarcoidosis. We report a rare case of pulmonary sarcoidosis with polyclonal B lymphocytosis of antibody independent stage in peripheral blood.

Adult↗

[Phenotypic analysis in peripheral blood lymphocytes of patients with pulmonary tuberculosis].

In order to clarify the immunological aspects of tuberculosis, phenotype of peripheral blood lymphocytes was analyzed in 96 patients with pulmonary tuberculosis and 43 normal controls. In tuberculosis, CD8 positive T cells were significantly decreased in comparison with normal controls and regarding expression of CD3, CD4, CD19, CD16 and gamma delta T cell receptor (TCR), there was no significant difference between tuberculosis and normal controls, though in tuberculosis CD4 positive T cells tended to be high as compared to normal controls. With respect to previous therapeutic condition, the group with previous chemotherapy had significantly high CD4 positive cells, low CD8 positive cells and low gamma delta TCR positive cells as compared to the group without previous chemotherapy. Between groups divided by Type or Expansion of pulmonary tuberculosis without previous chemotherapy, there was no significant difference regarding any surface markers. Regarding pulmonary tuberculosis with previous chemotherapy, the group of Type II had significantly high CD4 positive cells and low CD8 positive cells as compared to Type III, and in the group of Expansion 3, CD19 positive cells were significantly high as compared to Expansion 2. Characteristic of phenotype in peripheral blood lymphocytes of patients with pulmonary tuberculosis is predominant CD4 positive cells in a corresponding decrease in the proportion of CD8 positive cells and is no elevation of gamma delta TCR positive T cells.

Adolescent↗

[A case of plasma cell granuloma with good response to steroid therapy].

A 46-year-old man was admitted with complaints of fever, cough and anterior chest pain. Chest X-ray examination disclosed an infiltrative shadow in the right upper lung field and chest CT scan strongly suggested invasion of mediastinum and anterior chest wall. Therefore, steroid therapy was selected because biopsy specimen showed proliferation of fibroblasts and mononuclear cells mainly containing plasma cells with no evidence of malignancy. After steroid therapy, chest X-ray examination showed that the infiltrative shadow was greatly reduced. However, since infiltrative shadow was increased again at 3 years after the initiation of steroid therapy, right upper lobectomy was performed. Histopathological analysis of resected tumor demonstrated proliferation of mature plasma cells and fibroblasts in conjunction with minor infiltration of neutrophils and lymphocytes. At 18 months after operation, new shadows appeared in right S8 and S10 which were shown to have almost the same histological findings as the resected tumor. Steroid therapy was restarted, and then the size of shadows decreased. It is conceivable that steroid therapy is an effective therapy for pulmonary plasma cell granuloma, especially multifocal and relapsing cases.

Granuloma, Plasma Cell↗

Functional analysis of mononuclear cells infiltrating into tumors: establishment of a new system to obtain functionally active tumor-infiltrating cells.

We have demonstrated that tumor-infiltrating T cells play a crucial role in tumor growth. In order to investigate the precise function of tumor-infiltrating cells, we avoided the use of any enzyme for separation of tumor-infiltrating cells from the solid tumor mass and established a new system in which we could easily obtain functionally active tumor-infiltrating cells in large amounts from the peritoneal cavity of T-9 gliosarcoma-sensitized rats. In this system, viable T-9 cells were intraperitoneally administered and peritoneal exudate cells were recovered. Importantly, cells obtained from the intraperitoneal cavity are phenotypically and functionally indistinguishable from those obtained from subcutaneous tumor masses. Furthermore, injection of purified lymphocyte migration factor-b resulted in the accumulation of CD8 (+) cytotoxic T cells in the peritoneal cavity. Therefore, this system also provides a means by which the in vivo function of chemotactic factor can be tested.

Animals↗

Induction of killer cells from lymphocytes in pleural effusion of advanced lung cancer patients.

We analyzed the phenotype and cytotoxic ability of pleural exudative lymphocytes (PLEL) which were obtained from 18 advanced lung cancer patients. Freshly isolated PLEL were mainly CD4(+) T cells and had weak natural killer, autologous tumor killing and lymphokine-activated killer activities. After cultivation of PLEL with interleukin-2, cytotoxicity of PLEL against autologous tumor cells was increased at 2 weeks, but it was remarkably reduced at 4 weeks. When PLEL were stimulated by mitomycin C-treated autologous tumor cells during culture, autologous tumor killing activity of PLEL was significantly enhanced even after 4 weeks of cultivation. Cold target inhibition analysis and binding inhibition assays using monoclonal antibodies indicated that autologous tumor stimulation could induce major histocompatibility complex class I restricted cytotoxic T lymphocytes specific for autologous tumor cells in some cases.

Adenocarcinoma↗

Functional analysis of mononuclear cells infiltrating into tumors. V. A. soluble factor involved in the regulation of cytotoxic/suppressor T cell infiltration into tumors.

We have analyzed the mechanisms controlling the accumulation of cytotoxic/suppressor T lymphocytes in tumor tissues. We found that tumor-infiltrating helper/inducer T cells isolated from T-9 gliosarcoma-sensitized rats between 4 and 6 days after T-9 gliosarcoma inoculation produced a lymphocyte migration factor (LMF) during in vitro culture. Four peaks of LMF activity (A through D) were detected upon fractionation of LMF by using a Mono Q anion exchange column chromatography. Peak C exhibited the strongest activity among the four peaks of LMF. The action of peak C was chemotactic, but not chemokinetic. Peak C had an isoelectric point of 8.0 and a Mr of 26,000 Da. Only cytotoxic/suppressor T cells were found to be sensitive to peak C in vitro as well as in vivo. It is thus likely that peak C is responsible for the infiltration of cytotoxic/suppressor T cells into tumor tissues. The infiltration of lymphocytes into tumor tissues might also be regulated by the expression of lymphocyte sensitivity for LMF. The target molecule for LMF at 4 days may involve an asparagine-linked oligosaccharide.

Animals↗

Functional analysis of mononuclear cells infiltrating into tumors. IV. Purification and functional characterization of cytotoxic cell-generating factor.

Rat cytotoxic cell-generating factor (CGF) was purified from cell-free supernatants of a T cell hybridoma (6B2-B8) that constitutively produces CGF. CGF activity was assessed by its ability to generate cytotoxic cells against 51Cr-labeled T-9 cells from spleen cells of T-9-immunized rats. The purification scheme consisted of ammonium sulfate precipitation, AcA 54 gel permeation, Mono Q anion exchange chromatography, Superose 12HR 10/30 gel permeation, SDS-PAGE with subsequent electroelution, and ProRPC HR5/10 reverse phase column chromatography. Overall, CGF was purified approximately 13,000-fold, with a maximum 2.5% recovery of activity, and the sp. act. of the purified CGF was approximately 19,000 U/mg. The purified CGF is distinct from the other lymphokines such as IL-1, IL-2, IL-3, IL-4, T cell-replacing factor/IL-5, IL-6, and IFN-gamma. It is capable of promoting the generation of cytotoxic T cells from R1-10B5 (+) spleen cells of T-9-immunized rats and also stimulates a W3/25 (+) T cell hybridoma to express the IL-2R. The CGF has an apparent m.w. of 28,000 under non-reducing and 14,000 and 16,000 under reducing conditions. 125I-labeled CGF binds to normal thymocytes as well as splenic T cells. The highest level of binding of CGF was detected on splenic T cells derived from T-9-immunized rats that were previously shown to contain CTL precursors. The binding analysis with 125I-labeled CGF demonstrated that CGF binds to a specific cell surface molecule with an approximate m.w. of 60,000 to 70,000.

Animals↗

New monoclonal antibody, 1C5, reactive with human cervical adenocarcinoma of the uterus, with immunodiagnostic potential.

A murine monoclonal antibody, 1C5, was produced by fusion of spleen cells obtained from mice immunized with CAC-1, a human cell line of adenocarcinoma derived from uterine cervix, and NS/1 myeloma cells. 1C5 can be used for the staining of routine formalin-fixed and paraffin-embedded tissue sections. 1C5-defined antigen was found to have a molecular weight of 26,000. The 1C5-defined antigen was resistant to neuraminidase and trypsin treatment, but sensitive to periodate treatment, indicating that an epitope of the 1C5-defined antigen is a carbohydrate moiety. Immunohistochemical study using immunoperoxidase staining demonstrated that 1C5 reacted with 87% of adenocarcinomas of the uterine cervix, 39% of endometrial carcinomas of the uterus, 100% of ovarian mucinous cystadenocarcinomas, 43% of ovarian serous cystadenocarcinomas, 45% of adenocarcinomas of the colon, and 40% of gastric adenocarcinomas, thus showing the broad reactivity to adenocarcinoma cells of various origins. However, 1C5 did not show any reactivity to ectocervix epithelium, cervical intraepithelial neoplasia, or squamous cell carcinoma of the uterine cervix. In addition, adenocarcinoma of the uterine cervix exhibited strong cytoplasmic reactivity with 1C5, whereas endometrial carcinoma of the uterus showed the luminal reactivity. 1C5 also reacts with 95% ethanol-fixed malignant cells in cervical smears.

Adenocarcinoma↗

Functional analysis of mononuclear cells infiltrating into tumors. III. Soluble factors involved in the regulation of T lymphocyte infiltration into tumors.

We have analyzed the mechanisms controlling the accumulation of T lymphocytes in tumor tissues. Spleen cells, left or right popliteal lymph node cells, and tumor-infiltrating cells were obtained from tumor-inoculated rats and were cultured for 24 h. Culture supernatants were obtained and assessed for lymphocyte migration factor (LMF) activity with the use of a modified Boyden chamber. We found that tumor-infiltrating cells derived from T-9-sensitized rats produced LMF. Two waves of LMF production were observed. The first wave of LMF production was detected between 6 and 12 h (LMF-a) and the second wave of LMF production was detected between 4 and 6 days (LMF-4d and -6d) after tumor inoculation. The tumor-infiltrating cells consisted of heterogenous cell populations. We found that only tumor-infiltrating neutrophils of T-9-sensitized rats produced LMF-a. Five peaks of LMF (A through E) were detected upon fractionation of LMF-a using Mono Q anion exchange column chromatography. Peak D exhibited the strongest activity. The action of peak D was chemotactic, but not chemokinetic. The m.w. of peak D was 33,000 and 70,000. Only W3/25 (+) (helper/inducer) T cells were found to be sensitive to peak D. The production of LMF-a by purified tumor-infiltrating neutrophils in vitro is in agreement with the histologic observation that the infiltration of neutrophils precedes the appearance of W3/25 (+) T cells in tumor tissues of T-9-sensitized rats. It is thus likely that peak D of LMF-a is responsible for the infiltration of T lymphocytes into tumor tissues.

Animals↗

Immunotherapy of solid tumor by intratumoral infusion of lymphokine-activated killer cells.

Fifty million lymphokine-activated killer (LAK) cells were infused into rat T9 gliosarcoma tumors for 1 hr at an infusion rate of 0.1 ml/hr. Cultured normal spleen cells were infused into similar tumors as a control. The LAK cell-treated tumors began to regress at approximately 3 weeks after infusion and disappeared by 6 weeks, while the cultured normal spleen cell-treated tumors grew progressively. Immunohistochemical analysis demonstrated prominent infiltration of cytotoxic/suppressor T cells in the LAK cell-treated tumors, while few lymphocytes were recognized in the control tumors. These data suggested that LAK cells infused intratumorally might be capable of mediating tumor regression by inducing host immunity against the tumor.

Animals↗