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Biomedical subjects

K Shimokata

Publications and source records attributed to K Shimokata.

At least 181 records · Page 10Linked to original sources

Human alveolar macrophages of anergic patients with lung cancer lack the responsiveness to recombinant interferon gamma.

We studied the effect of recombinant interferon gamma (rIFN-gamma) on the phagocytic and bactericidal actions in human alveolar macrophages (AM) of patients with pulmonary tuberculosis and lung cancer. Treatment with 100 or 1,000 U/ml of rIFN-gamma for 24 hours resulted in an increased percentage of AM ingesting bacillus Calmette-Guérin (BCG) and an increased number of ingested BCG in individual AM in tuberculin-positive patients with lung cancer and pulmonary tuberculosis. The rIFN-gamma treatment also showed increased killing activity of AM in tuberculin-positive patients. However, rIFN-gamma treatment of AM in tuberculin-negative anergic patients with lung cancer did not induce the increase of phagocytic and killing activities against BCG. These results suggest that responsiveness and activation of AM to rIFN-gamma are inhibited in the anergic environment.

Aged↗

Cytokine content in pleural effusion. Comparison between tuberculous and carcinomatous pleurisy.

Tuberculous pleurisy is a good model for resolution of local cellular immunity. It would be expected that tuberculous pleural fluid contains a variety of immunologically important cytokines because of the accumulation of immunocompetent cells in the pleural cavity. We studied interleukin 1 (IL-1), interleukin 2 (IL-2), and interferon gamma (IFN-gamma) levels in pleural fluid of 20 patients with tuberculous pleurisy and compared them with those in pleural fluid of 20 patients with malignant pleurisy. We also evaluated adenosine deaminase (ADA) levels in both effusions. Tuberculous pleural fluid had higher levels of IL-1, IL-2, IFN-gamma, and ADA than malignant pleural fluid. Although the difference of IL-1 level between tuberculous and malignant pleural fluid was modest, that of IL-2, IFN-gamma, and ADA was dominant. These findings suggest that activated T lymphocytes in tuberculous pleural fluid concern the production of lymphokines at the morbid site and they effectively exert local cellular immunity through the action of such lymphokines.

Adenosine Deaminase↗

Chest CT combined with artificial pneumothorax: value in determining origin and extent of tumor.

To determine the presence of chest wall and mediastinal invasion by lung cancer and to establish the origin of chest tumors, we studied 12 patients with intrathoracic tumors by using chest CT combined with artificial pneumothorax. Six patients had primary lung cancer, two had metastases, and one each had neurofibroma, pericardial cyst, chondroma of the rib, and malignant mesothelioma. All 12 tumors abutted the chest wall or mediastinum and could not be separated by conventional CT. Between 400 and 800 ml of air was injected into the pleural space before a second CT scan was obtained. No invasion was found at surgery in cancers that were separated from chest wall or mediastinum on CT scans. Surgery revealed chest wall invasion in three patients in whom the CT scans showed that the tumor was not separated from the chest wall. Only one patient with a tumor that was not separated from the mediastinum on CT did not have mediastinal invasion: in this case, only adhesions were found at surgery. Thus, in the eight patients with primary lung cancer and metastasis, sensitivity, specificity, and accuracy were 100%, 80%, and 88%, respectively. In four patients with mediastinal or pleural tumor, CT combined with pneumothorax was useful for establishing the origin of tumors. In all, 11 of the 12 patients were correctly evaluated by using this method. No complications occurred, except for mild chest discomfort in one patient. This study suggests that chest CT combined with artificial pneumothorax is useful for the evaluation of the extension of lung cancer into the chest wall and mediastinum and for the diagnosis of the site of origin of intrathoracic tumors.

Adult↗

Pharmacokinetics of an etoposide infused over three days: concomitant infusion with cisplatin.

The pharmacokinetics of a 72-hour infusion of 240 mg/m2 etoposide administered concurrently with 90 mg/m2 cisplatin was studied in 12 lung cancer patients. The area under the curve (AUC), elimination half-life, steady state concentration, systemic clearance, renal clearance of etoposide and distribution volume at steady state were 225.4 +/- 39.2 micrograms x h/ml, 8.1 +/- 3.4 h, 3.1 +/- 0.6 micrograms/ml, 18.8 +/- 3.1 ml/min/m2, 3.1 +/- 1.4 ml/min/m2, 9.6 +/- 3.8 l/m2, respectively, which were in accordance with those reported previously in patients treated with etoposide alone. Although concentration at 24 hours, total bilirubin level and total protein level were correlated with the AUC which in turn correlated with hematologic toxicity, the variables were not predictive of hematologic toxicity. We conclude that the concomitant administration of cisplatin at a dose level of 30 mg/m2/day might not affect the pharmacokinetics of prolonged etoposide infusion.

Aged↗

Growth restriction of negative-strand-RNA viruses in a rat 3Y1 cell line.

A rat fibroblast cell line, 3Y1 is nonpermissive for infection by several negative-strand-RNA viruses including influenza virus A, Sendai virus, Newcastle disease virus and vesicular stomatitis virus (VSV), but not refractory to that of a positive-strand-RNA virus, Sindbis virus. To elucidate the mechanism of the restricted viral growth, we compared the replication pattern of VSV in 3Y1 cells and in baby hamster kidney cells, which are fully permissive for those viruses. The results indicated that the restriction was imposed predominantly on the transcription of the viral RNA. The subsequent steps such as protein synthesis and nucleocapsid assembly appeared to occur normally, although these levels remained low due to the restricted transcription. Virus attachment onto, and penetration into, 3Y1 cells were also not restricted.

Animals↗

Ifosfamide, cisplatin, vinblastine combination chemotherapy in the treatment of advanced non-small-cell lung cancer.

A total of 42 evaluable patients with previously untreated advanced non-small-cell lung cancer were treated with a combination of cisplatin (80 mg/m2, day 1), vinblastine (5 mg/m2, days 1 and 15), and ifosfamide (1.2 g/m2, days 1-3). In all, 1 complete response and 15 partial responses were obtained, for an overall response rate of 38% (95% confidence limits, 23.6%-54.4%). The median duration of response was 15 weeks, and the median overall survival was 56 weeks. Toxicity mainly consisted of moderate to severe alopecia in 28 patients (67%), moderate to severe nausea and vomiting in 27 subjects (64%), and leukopenia comprising less than 1,000 leukocytes/mm3 in 6 cases (14%). In all, 16 patients (38%) had microscopic hematuria (WHO grade 1), but no hemorrhagic cystitis was documented. Although this three-drug combination appears to have moderate antitumor activity against non-small-cell lung cancer, the addition of ifosfamide to the combination of cisplatin and vinblastine did not seem to improve the response rate.

Adult↗

Interleukin 2 and interferon-gamma activities of mononuclear cells from regional lymph nodes in patients with gastric cancer.

The interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) activities of regional lymph node mononuclear cells (LNMC) were studied in 22 patients with gastric cancer. Regional LNMC could produce high levels of IL-2 and IFN-gamma independent of the disease extension or the location of the lymph nodes. The activities of peripheral blood mononuclear cells (PBMC) from cancer patients were decreased especially in advanced disease compared to controls. The lymph node CD4+ cells were responsible for the bulk of IL-2 activity, whereas both CD4+ and CD8+ cells were equally capable of producing IFN-gamma. The proportion of T cells in LNMC was similar to that seen in PBMC, however, CD4+ cells predominated over CD8+ cells in the lymph nodes, contributing to higher activities of IL-2 and IFN-gamma in LNMC. Furthermore, significant cytotoxic activity could be induced from PBMC using the culture supernatant derived from autologous LNMC in cancer patients. This study suggests that regional lymph nodes are strategically located near the tumor and the local cells are capable of producing high levels of IL-2 and IFN-gamma.

CD4-Positive T-Lymphocytes↗

Bronchoscopic and cytopathological findings of tracheobronchial involvement in esophageal carcinoma.

To evaluate the usefulness of bronchoscopic and cytopathologic examinations for tracheobronchial involvement of esophageal carcinoma, we reviewed 14 cases of esophageal carcinoma suspected of tracheobronchial invasion. Two cases underwent bronchoscopy for postoperative respiratory symptoms, and both revealed endotracheal tumor growth and proved positive at brush cytology and biopsy. Among nine cases submitted to preoperative examination, bronchoscopy showed only protrusion in four cases, and redness with mucosal protrusion in five cases. Two of the latter evidenced cancer cells on brushing specimen, and their prognosis was poor. The remaining three cases underwent bronchoscopy for preoperative severe respiratory symptoms. Tumor growth was noted in two of them, and cytology or biopsy was positive. We conclude that bronchoscopy for tracheobronchial involvement of esophageal carcinoma plays a major role in the diagnosis of extra-esophageal extension. Because of the anatomical situation, biopsy is sometimes difficult. Brush cytology is important in the case of mucosal protrusion and redness.

Aged↗

Antipurified-protein-derivative antibody in tuberculous pleural effusions.

Using ELISA, we studied anti-PPD antibody values in 31 tuberculous and 39 carcinomatous pleural effusions. Mean ODI values of anti-PPD IgG, IgA and IgM antibodies in tuberculous pleural effusions were higher than those in carcinomatous pleural effusions (p less than 0.01 in IgG and IgA, p less than 0.05 in IgM antibodies). We also analyzed the detected antigens in PPD and BCG whole cell fraction recognized by IgG antibody in tuberculous pleural effusions. Among heteromolecular components, the antigen band from 25 to 40 Kd region was most frequently stained. This antigen was heat-stable, contained sugar components, and included no disulfide bonds.

Adolescent↗

High dose chemotherapy with autologous bone marrow transplantation for limited small cell lung cancer.

UNLABELLED: In 1980 we initiated a pilot study of high dose chemotherapy intensified with autologous bone marrow transplantation (ABMT) for seven patients with limited small cell lung cancer. Six patients were given the ABMT initially while one male patient received the ABMT late to intensify three courses of induction therapy. He further received radiotherapy and underwent a left pneumonectomy and adoptive immunotherapy, because the presence of residual tumor cells, and has maintained disease-free survival for over 117 weeks. Among the first six patients there were two with complete responses, two with partial responses and one who experienced no change, a total response rate of 80%. One patient died of cardiac tamponade at day 7 and could not be evaluated. The median survival time of 41 (range 34-108) weeks was not encouraging. IN CONCLUSION: an increased drug dose with ABMT to intensify the chemotherapy provided disappointing results both when the ABMT was used initially and when it was given late, after induction chemotherapy.

Adult↗

[The alpha subunits of the GTP-binding proteins, Go and Gi2 in lung cancer].

The alpha subunits of the GTP-binding proteins, Go and Gi2, in sera, tissues, and pleural effusions have been studied, using an enzyme immunoassays system. The Gi alpha concentrations were found increased in the pleural effusions of patients with a small cell lung cancer, as compared to patients with a nonsmall cell lung cancer. Both GTP-binding proteins, however, were not elevated in the sera of patients with a lung cancer. Thus, an evaluation of the amount of Go alpha in the pleural effusion is thought to be a useful tumor marker of small cell lung cancers, elevating the specificity of a combination assay with other markers, NSE or CKBB.

Adenocarcinoma↗

[A combined anti-emesis therapy of oral prednisolone and alprazolam for cisplatin-induced delayed emesis].

To evaluate the efficacy of a combined therapy of prednisolone and alprazolam for controlling cisplatin-induced delayed emesis, a study involving 14 non-small cell lung cancer patients receiving cisplatin (80 mg/m2) was conducted. Seven of these patients were given oral prednisolone at a dose of 30 mg/day for 5 days, then, 15 mg/day for 2 days, and with alprazolam at a dose 1.2 mg/day for 7 days. The other 7 patients were given an oral metoclopramide at a dose of 1 mg/kg/day for 5 days, and at 0.5 mg/kg/day for 2 days. All patients received 2 courses of chemotherapy and the same assigned regimen. Five of the 7 patients who had received prednisolone and alprazolam experienced no emesis, in contrast to only 1 patient who experienced no emesis from taking oral metoclopramide (p less than 0.05). Further, the duration of anorexia was shorter in those who received oral prednisolone with alprazolam. Thus, a combined therapy of oral prednisolone and alprazolam appears to be effective for controlling cisplatin-induced delayed emesis. Further evaluation and study, however, are necessary.

Administration, Oral↗

Immunoblot analysis of Dermatophagoides farinae antigen.

We isolated the allergenic components of Dermatophagoides farinae (D. farinae) body extracts and determined the frequencies and specificities of IgE, IgG, and IgG4 antibodies binding to components of D. farinae extracts by use of immunoblot technique. A total of 29 IgE-binding components of D. farinae extracts were identified and distributed over the molecular weight range of 13 to 140 kilodaltons (kD). Each component had 3% to 73% frequencies of recognition by individual patient serum, and the major antigenicity of D. farinae was considered to exist in components of 13 to 16 kD, 25 to 30 kD, and 43 to 60 kD. These observations suggested that antigenicity of D. farinae is not restricted to one major allergen, but several components account for the total allergenic activity of D. farinae. We could also demonstrate 27 IgG-binding components of D. farinae antigen. Their frequencies and strength of binding were similar to IgE. IgG4 antibodies in patients with bronchial asthma bound to components with molecular weights 13, 25, 43, and 50 kD had relatively low frequencies of binding to IgE antibodies.

Allergens↗

[Evaluation of imipenem/cilastatin sodium in the treatment of respiratory tract infections].

Imipenem/cilastatin sodium (IPM/CS) was administered to 55 patients with respiratory tract infections (RTI). A clinical evaluation of IPM/CS was carried out in 51 patients, 28 with pneumonia, 4 with pulmonary abscess, 1 with pyothorax, 6 with bronchitis, 9 with bronchiectasis, 1 with diffuse panbronchiolitis and 2 with RTI with chronic obstructive pulmonary disease, and the clinical efficacy rate was 78.4%. Causative organisms were isolated in 23 strains out of 20 patients, such as Staphylococcus aureus 4 strains, Staphylococcus epidermidis 1 strain, Streptococcus pneumoniae 1 strain, Branhamella catarrhalis 1 strain, Haemophilus influenzae 2 strains, Klebsiella pneumoniae 4 strains, Pseudomonas aeruginosa 6 strains, Pseudomonas sp. 1 strain, Acinetobacter calcoaceticus 1 strain, Acinetobacter sp. 1 strain and glucose non-fermentative Gram-negative rod 1 strain. An eradication rate of 70.6% was obtained. An overall eradication rate of main causative organisms in RTI including S. aureus, S. pneumoniae, H. influenzae and K. pneumoniae was 75.0%. Clinical adverse effects were observed in 5 patients, and these were eruption in 2, itching in 1, vomiting in 1 and drug fever in 1. Abnormalities in laboratory test results were observed in 8 patients. These disappeared or returned to normal values after completion or discontinuation of IPM/CS administration. IPM/CS appears to be a useful antibiotic for the treatment of RTI, especially severe infections.

Adult↗

Phenotypic characterization of alveolar capillary endothelial cells, alveolar epithelial cells and alveolar macrophages in patients with pulmonary fibrosis, with special reference to MHC class II antigens.

Major histocompatibility complex (MHC) class II antigens are essential in the presentation of antigens to T lymphocytes, and cells expressing MHC class II antigens are known to play a role as antigen presenting cells (APC). We investigated the distribution of MHC class II antigens and the reactivity of monoclonal antibodies OKM1 and OKM5 in normal and fibrotic lungs immunohistochemically. The results showed that alveolar capillary endothelial cells (ACEnd) expressed MHC class II antigens and were reactive with OKM5 in both normal lungs and the non-thickened parts of alveolar septa of pulmonary fibrosis. However, ACEnd did not express MHC class II antigens and were not reactive with OKM5 in thickened alveolar septa of pulmonary fibrosis. Type II alveolar epithelial cells (AEp) proliferating and replacing type I AEp in pulmonary fibrosis expressed MHC class II antigens strongly. Alveolar macrophages expressed MHC class II antigens strongly and reacted with OKM1 in pulmonary fibrosis, especially in alveolar spaces. These findings suggest that the phenotypic changes of ACEnd may be involved in the process of pulmonary fibrosis, and type II AEp and alveolar macrophages in the parts of thickened alveolar septa may play a role as APC.

Antibodies, Monoclonal↗

Mode of alloantibody-mediated blockade of allo-sensitization for tumor allograft rejection.

The mode of alloantibody-mediated inhibition of allo-sensitization for tumor allograft rejection was studied. Relatively small amounts of anti-H-2d alloantiserum administered shortly before or after injection of allogeneic spleen cells blocked the allo-sensitization for second-set tumor allograft rejection. In contrast, the alloantiserum injected shortly before inoculation of tumor barely enhanced the tumor growth. The passively administered alloantiserum inhibited the sensitization for allospecific cytotoxic T lymphocyte responses in vitro. Further study revealed that the allo-sensitization could be blocked with antiserum specific against only one of the expressed H-2 antigens on stimulator cells. Correspondingly, H-2Dd-monospecific monoclonal antibody (IgG2a) was effective in inhibiting the sensitization with cells expressing multiple H-2 alloantigens. These results suggest that antibody-mediated inactivation of stimulator cells as a whole is an important mechanism of the allograft enhancement.

Animals↗

Carotenoid pigments of genus Rhodococcus.

A study of carotenoid pigments of the genus Rhodococcus was carried out. According to carotenes contained, Rhodococcus species were divided into three groups: the first group of Rhodococcus luteus, R. coprophilus, R. lentifragmentus, and R. maris, which formed beta-carotene; the second group of R. equi, R. rubropertinctus, R. aichiensis, R. sputi, R. chubuensis, R. obuensis, R. bronchialis, R. roseus, R. rhodochrous, R. rhodnii, and R. terrae, which formed gamma-carotene-like substance; and the third group of R. aurantiacus, which formed neither carotene. Other carotenoid pigments were different according to the species.

Carotenoids↗