[Release of slow-reacting substance of anaphylaxis from peripheral blood leukocytes challenged with a specific antigen (mite) in patients with atopic bronchial asthma].
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Biomedical subjects
Publications and source records attributed to K Shimokata.
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T-2588 was used on 55 patients with respiratory tract infections and 44 cases were evaluated; 23 patients with pneumonia, 12 patients with acute bronchitis, 2 patients with chronic bronchitis, 1 patient with diffuse panbronchiolitis and 6 patients with bronchiectasis with infection. Clinical effects of T-2588 were as follows; excellent in 6 and good in 28 patients. The efficacy rate was 77.3% (34/44). Bacteriological effects of T-2588 were prominent in 8 patients infected with B. catarrhalis, H. influenzae, K. pneumoniae and E. coli, but not in a patient infected with P. putida. The elimination rate was 90.0% (9/10 strains). As side effects, stomatitis, anorexia, diarrhea X vomiting and pruritus were observed in one patient each. Abnormal laboratory findings were observed in 4 patients with elevated GOT and/or GPT. These side effects and abnormal laboratory findings were not serious. The usefulness of T-2588 was 68.2% (30/44). Therefore, T-2588 is a useful drug and its effects are promising in clinical management of respiratory tract infections.
The afferent arc of the in vivo cytotoxic T-cell immunity assessed by second set rejection of ascitic allogeneic tumors was shown to be depressed by bacterial lipopolysaccharide (LPS) that was administered simultaneously with or 1 day before injection of allogeneic spleen cells as stimulators. Two different LPSs from Escherichia coli O55 and Klebsiella O3 displayed similar activities whereas dextran sulfate, concanavalin A, or poly A:U was not effective. Stimulator activities of allogeneic cells was not directly modified by LPS. Any definite suppressor activity on afferent or efferent arc of the T-cell response was not demonstrable in mice receiving LPS and allogeneic cells. Further, the LPS effect for immune depression was not diminished by whole body X-ray irradiation to the recipient at 300 R, which ablated the B-cell reactivity to LPS for polyclonal activation, or by treatment of the recipient with carrageenan, a known toxic agent to macrophages. It was suggested from these results that LPS suppresses the cytotoxic T-cell immunity by modulating responder T cells to be temporarily refractory to the allogeneic stimulus rather than by activating suppressor cells such as radiation-sensitive lymphocytes and carrageenan-sensitive macrophages.
Two kinds of the third domain, either with or without a carbohydrate chain, were prepared from chicken ovomucoid. The immunoreactivity of the domain preparations to human IgE antibody directed against ovomucoid was examined by using the sera from patients of egg allergy. About 30% of the serum antibody to ovomucoid reacted with the carbohydrate-containing domain, whereas little or no antibody with reactivity to the carbohydrate-free domain was detected, suggesting that the carbohydrate chain attached to the third domain played an important role in antigenic determinants of the carbohydrate-containing third domain against the human IgE antibody.
Current interpretation based on analytical in vitro works that actions of Ia antigens and accessory cells such as macrophages and dendritic cells are crucial for inducing cytotoxic T cell responses to class I major histocompatibility complex (MHC) alloantigens has been challenged by experiments performed in a newly developed system handling in vivo cytotoxic T cell immunity. We first characterized the transplantation immunity for second-set rejection of ascitic tumor allografts as principally induced by allogeneic stimulator cells via direct pathway, and as exclusively mediated by class I MHC alloantigen-specific in vivo cytotoxic T cell activity. By comparison of activities of limiting effective doses (10(4)-10(5) cells per mouse) of various stimulator cells in this defined system, we could demonstrate that genetic disparity at the D region of H-2 to the recipient is just enough for inducing the immunity, and presence of allogeneic or syngeneic Ia antigens in addition to H-2D alloantigens on stimulator cells does not give any premium effect. Further study revealed that allogeneic peritoneal cells rich in macrophages or glass-adherent spleen cells enriched for dendritic cells are not stronger stimulators than allogeneic adherent cell-depleted spleen cells and semi-allogeneic thymocytes. These results fit with the alternative concept that the physiological pathway inducing in vivo cytotoxic T cell immunity for graft rejection entirely depends on class I MHC antigens on live lymphocytes as self-supported stimulators, and does not crucially involve additional stimulator activities of Ia antigens and special accessory cell types, which must be in vivo concerned with induction of other types of transplantation immunity.
As an aid in the differential diagnosis of exudative pleural effusions, tumor markers were investigated. We measured immunosuppressive acidic protein (IAP), carbohydrate antigen 19-9 (CA 19-9), tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), adenosine deaminase (ADA), and alpha 1-acid glycoprotein (AGP) in the pleural fluid of 36 patients with carcinomatous pleural effusions and of 35 patients with tuberculous pleurisy because we have frequently found these diseases to be associated with exudative pleuritis. Tuberculous pleural effusions had significantly higher levels of IAP, ADA, and AGP than carcinomatous effusions (p less than 0.005). On the other hand, CEA, CA 19-9, and TPA were significantly higher in carcinomatous pleural fluids than in tuberculous fluids (p less than 0.05). There was a correlation between IAP and AGP levels, and their specificity was low. Therefore, combined assays of CEA, CA 19-9, and ADA may be useful in distinguishing pleural effusions due to malignancies from those of tuberculous origin.
We studied the role of sputum cytology and factors influencing the rate of positivity of sputum cytology in 103 patients with lung cancer. Sputum cytology was positive in 71.8% of these patients. Of 647 specimens submitted for sputum cytology, 610 were evaluable and the positivity rate was 43.6%. Forty-eight patients had at least six sputum cytology examinations. The rate of positivity for each of these examinations was between 31.3% and 50.0%, and the cumulative rate of positivity in these 48 patients was 77.1% at the sixth examination. Factors influencing the positivity rate were the histology of the tumor, tumor size, the site of the tumor, admixture with blood and the degree of surface necrosis of the tumor. The histology suspected from the sputum cytology coincided well with that determined at the operation or necropsy in adenocarcinoma, squamous cell carcinoma and small cell carcinoma, but not in large cell carcinoma.
A clinical trial of a new semi-synthetic podophyllotoxin, VP-16, was undertaken in patients with primary lung cancer; 56 of the 81 evaluable patients had small cell carcinoma, 9 adenocarcinoma, 8 epidermoid carcinoma, 7 large cell carcinoma, and 1 adenosquamous carcinoma. A dose of 200 mg/body/day orally for 5 consecutive days was administered every 3 to 4 weeks. Partial response (PR) was attained in 19 out of 81 (23%) and PR + MR was 35 out of 81 (43%). PR and minor response (MR) were seen as follows; small cell carcinoma, 17 PR (30%), 13 MR; epidermoid carcinoma, 2 PR (25%), 1 MR; adenocarcinoma, 1 MR; adenosquamous carcinoma, 1 MR. The dose-limiting factor was leukopenia, while thrombocytopenia was experienced in 2 cases. Clinical toxicities noted were anorexia, nausea, vomiting, stomatitis, diarrhea and alopecia, but these were well tolerated in all cases. The result indicated that VP-16 has considerable efficacy in small cell carcinoma and epidermoid carcinoma of the lung and hence its usefulness in combination chemotherapy was suggested.
Ceftizoxime (CZX) was used for 33 patients with respiratory tract infections; 22 patients with pneumonia, 3 patients with pulmonary abscess, 4 patients with diffuse panbronchiolitis and 4 patients with acute exacerbation of bronchiectasia. Clinical effects of CZX were evaluated in 33 patients; excellent in 16 and good in 14 patients. The efficacy rate was 91%. Bacteriological effects of CZX were prominent in 7 patients infected with S. pneumoniae, H. influenzae, K. pneumoniae and Citrobacter, but not in a patient infected with P. aeruginosa. The elimination rate was 92% (12/13). As the side effects, exanthema in 1 patient and gastrointestinal symptoms (nausea and vomiting) in 1 patient were observed. However, they improved without any treatment by cessation of CZX use. Abnormal laboratory findings were observed in 2 patients with elevated GOT and/or GPT. They normalized after cessation of drug. The usefulness of CZX was 82% (27/33). Therefore, CZX is a very useful drug and its effects are promising in clinical management of respiratory tract infections.
Aztreonam (E-0734, AZT) was administered to pneumonia and chronic respiratory tract infections. The results were as follows: AZT was administered to 29 patients. Twenty-six cases were evaluable and 3 cases were excluded from evaluation of efficacy because 1 was Gram-positive infection, 2 were unclear symptom of infection. Pneumonia was 4 cases. Chronic respiratory tract infections were 22 cases. Clinical efficacy was judged as follows; excellent in 7 cases, good in 10 cases, fair in 5 cases and poor in 4 cases, then the efficacy rate was 65.4%. Efficacy rate in pneumonia, acute aggravation of diffuse panbronchiolitis and bronchiectasis with infection was 50%, 67% and 83%, respectively. Bacteriological response was judged on 21 cases with eradication rate was 66.7%. Bacteriological response classified by pathogen was as follows: All 6 isolates of H. influenzae, 2 in 6 isolates of P. aeruginosa, 4 in 5 isolates of H. parainfluenzae and all 3 isolates of K. pneumoniae were cleared. Total eradicated rate was 74.1%. Eruption was observed in 1 case as side effect. Abnormal laboratory findings were observed in 4 cases. Elevation of GOT and GPT was in 3 cases. Increase of eosinophil and basophil was in 1 case. AZT was considered to be a useful antibiotic for the treatment of respiratory tract infections, especially chronic respiratory tract infections, caused by Gram-negative pathogens.
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An antiemetic combination of metoclopramide and methylprednisolone was administered to 16 lung cancer patients receiving cisplatin (80 cmg/m2) alone or in combination with other drugs. Metoclopramide was administered four times intravenously at a dose of 1.5 mg/kg. Methylprednisolone was administered three times intravenously at a dose of 125 mg. Sixteen patients received a total of 34 chemotherapy courses. No vomiting occurred in 70% of 34 chemotherapy courses and mild emesis (one or two vomiting episodes) occurred in 18% of chemotherapy courses. Side effects were minimal and included mild sleepiness (nine patients), diarrhea (three patients), and hiccups (three patients). It is concluded that a combination of metoclopramide and methylprednisolone is very effective in preventing cisplatin-induced vomiting.
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A carrier culture of L cells persistently infected with Sendai virus (steady state) designated as L-Sendaits cells was established with a temperature-sensitive strain of the virus. When interferon was added to culture fluids from the start of the cultures at permissive (35 degrees C) or non-permissive temperature (38 degrees C), cell-associated infectivity was unaffected at 35 degrees C, while it was unexpectedly enhanced at 38 degrees C, although the cell-associated infectivity was titrated after further incubation at 32 degrees C for 2 days. The titer of cell-associated infectivity was increased by subculturing in the continuous presence of interferon at 38 degrees C. The effect of interferon on the paradoxical enhancement of cell-associated infectivity was shown to be dose dependent. When L-Sendaits cells were successively subcultured 6 times at 38 degrees C in the continuous presence or absence of interferon, more than 95 per cent of the cells contained a detectable amount of nucleocapsid (NP) antigen in the presence of interferon, whereas the antigen could be detected in only 30-40 per cent of the cells subcultured in the absence of interferon. Only when the cells subcultured at 38 degrees C in the presence of interferon were transferred to permissive temperature, could the distinct hemadsorbing and cell-associated hemagglutinating activities and the release of virus particles, as measured by hemagglutinating activity in the culture fluids, be detected. Cells subcultured in the presence of interferon accumulated more virus polypeptides than in the absence of interferon. Accumulation of virus specific RNA in the cells subcultured in the presence of interferon was about twice as much as that in the absence of interferon. Larger sized RNA (probably 50S) was the major species and two smaller RNAs could be detected in both the treated and untreated cells. When L-Sendaits cells were cultured at 38 degrees C in the presence of interferon, their multiplication was clearly inhibited. However, the cells which were subcultured twice at 38 degrees C in the continuous presence of interferon acquired resistance to the anti-cell proliferative action of interferon. Interestingly, the conversion of the sensitive state to resistant state of the cells was reversible.
Murine allogeneic red blood cells (RBC) induce primary IgM antibody responses to H-2 alloantigens T-cell-independently (TI). In this study we showed that bacterial lipopolysaccharide (LPS), which should activate B lymphocytes polyclonally, could not trigger an anti-H-2d plaque-forming cell response. We then demonstrated that administration of LPS (on days 0-1) with allogeneic RBC suppressed the response of mice to H-2d, while giving LPS 4-6 days after RBC augmented the response. In contrast, LPS did not enable allogeneic spleen cells to induce an anti-H-2d response. Additional experiments showed that the allogeneic RBC behave as a TI class 2 antigen. It was concluded from these results that allogeneic RBC display a peculiar activity that exclusively triggers a TI type-2 B cell response that cannot be initiated by LPS and is modulated by LPS in an abnormal fashion. The possible significance of this finding in the mechanism of occurrence of natural H-2-specific IgM alloantibodies in aged mice is discussed.
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