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Biomedical subjects

A Okano

Publications and source records attributed to A Okano.

At least 109 records · Page 6Linked to original sources

Long-term effects of ofloxacin on clinical courses in patients with diffuse panbronchiolitis.

To ascertain the long-term effects of ofloxacin (OFX) on clinical parameters in cases of diffuse panbronchiolitis (DPB), we treated 18 patients with this disease with OFX and compared the clinical findings before and after treatment. Pulmonary function tests including percent vital capacity, arterial oxygen tension and arterial-alveolar oxygen tension difference significantly improved with OFX. In addition, the incidence of acute exacerbation and the duration of hospitalization were reduced. These observations indicate that OFX is a useful drug for the management of chronic respiratory infections such as DPB.

Bronchiolitis↗

[Fulminant mycoplasma pneumoniae infection presenting with Stevens-Johnson syndrome & respiratory failure].

An 18-year-old man was admitted to Hamamatsu University Hospital on February 15, 1985, with high fever, vesicular and papular rash involving the skin and mouth, conjunctivitis, productive cough and dyspnea. A diagnosis of Stevens-Johnson syndrome was made by skin biopsy, and chest X-ray showed an infiltrate in the right lower lung filed. Despite treatment with corticosteroids and antibiotics, the mucocutaneous lesions did not heal, and the pneumonia progressed to both lung fields. Because the patient had developed dyspnea, a tracheotomy was performed, mechanical ventilatory support was instituted, and high-dose corticosteroid therapy was started. However, jaundice due to intrahepatic cholestasis, hematuria, hematochezia, sepsis, and subcutaneous and mediastinal emphysema ensued, and the patient died of respiratory failure on March 1. Postmortem examination of the lung demonstrated diffuse alveolar damage. The complement-fixation titer for Mycoplasma was 1:64, compared with a level of less than 1:4 on admission. This case was though to be one of fulminant Mycoplasma pneumoniae infection presenting with Stevens-Johnson syndrome, respiratory failure and other extra-pulmonary complications.

Adolescent↗

[Clinicopathologic study of various lung diseases with bronchiolitis obliterans organizing pneumonia (BOOP) pattern in open lung biopsy].

The histologic findings of BOOP are nonspecific, and the diagnosis of idiopathic BOOP is one of exclusion. We studied the clinicopathologic features of various lung diseases with histopathological appearance of bronchiolitis obliterans organizing pneumonia (BOOP) pattern in open lung biopsy specimens. The 17 patients with BOOP pattern studied included idiopathic BOOP (n = 7), unclassified interstitial pneumonia (n = 1), collagen vascular disease (n = 3, RA 1, PM/DM 2), hypersensitivity pneumonitis (HP, n = 2), eosinophilic pneumonia (EP, n = 1), multiple lung abscesses (n = 1), limited form of Wegener's granulomatosis (n = 1), and pneumocystis carinii pneumonia associated with adult T cell leukemia (n = 1). There were no differences in clinical symptoms, laboratory data, respiratory function, and cytological findings in bronchoalveolar lavage fluid (BALF) between cases of idiopathic BOOP and other lung diseases. The duration of clinical symptoms was less than one year in 16 patients (one case had no symptoms). Chest X-rays showed bilateral patchy, nodular, or reticular shadows in all cases. Multiple patchy migratory shadows were only observed in cases of idiopathic BOOP or EP. Organizing pneumonia was recognized in the transbronchial lung biopsy specimens of all patients with idiopathic BOOP, HP or EP. Regarding prognosis, relapses occurred in idiopathic BOOP (n = 5), polymyositis, EP, limited form of Wegener's granulomatosis, and Pneumocystis carinii pneumonia. Four patients with idiopathic BOOP relapsed when steroid therapy was decreased or stopped. These findings indicate that idiopathic BOOP should be differentiated from other lung diseases, and these patients should be followed for a long period of time.

Adult↗

[Pulmonary interstitial pneumonia in association with Hermansky-Pudlak syndrome].

A 33-year-old albinotic woman whose parents were consanguineous was referred to our hospital with dry cough, dyspnea on exertion, and diffuse reticulonodular shadows on chest X-ray film. She had no apparent bleeding diathesis, although platelet serotonin content and ATP release were reduced. Open lung biopsy revealed pulmonary interstitial fibrosis with deposition of ceroid-like material with alveolar and interstitial macrophages. From these findings, the diagnosis of Hermansky-Pudlak syndrome (HPS) with interstitial pneumonia was mode. The reported characteristics of pulmonary interstitial pneumonia associated with HPS are occurrence of this disease in the thirties to forties, diffuse reticulonodular shadows in all lung fields with sparing of the subpleural zones, and bullous formation in the upper lobes. Progression usually occurs to diffuse interstitial fibrosis, but these is little decrease in lung volume. The prognosis of HPS with interstitial pneumonia is worse than that of uncomplicated HPS, and patients die of respiratory failure within 1 to 6 years after diagnosis. Steroid therapy is not effective.

Adult↗

[Cisplatin, doxorubicin and vindesine in the treatment of advanced non-small cell lung cancer].

Thirty-seven patients with advanced non-small cell lung cancer were enrolled to evaluate a combination chemotherapy of cisplatin (80 mg/m2), doxorubicin (30 mg/m2) and vindesine (2 mg/m2 x 3). The overall response rate was 27% with ten partial remission. The median survival of whole patients was 11.4 months. The calculation of median survival of the patients with partial remission has not been completed: nine of ten patients have been still alive during the follow-up period of 4 to 16 months. The survival of the patients with PR was significantly different from those of the patients with NC or PD. The major toxicity was myelosuppression. These results indicate that a combination chemotherapy with cisplatin, doxorubicin and vindesine is a moderately effective regimen against non-small cell lung cancer compared to others.

Adult↗

[A case of Klinefelter syndrome associated with lung cancer and RA lung].

A 50-year-old man was admitted for evaluation of an abnormal shadow on a chest X-ray. He had experienced pain and swelling in his fingers for three years. He had also noticed that he is impotent. The diagnosis of Klinefelter syndrome and rheumatoid arthritis (RA) was established by clinical findings and chromosomal analysis. Transbronchial biopsy revealed adenocarcinoma and right upper lobectomy was performed. Open lung biopsy showed interstitial pneumonia. In conclusion, we reported a rare case of lung cancer, rheumatoid arthritis and RA lung associated with Klinefelter syndrome.

Adenocarcinoma↗

[Gene-transfer into bone marrow cells].

We have intended to improve gene-transfer technique into hematopoietic stem cells for somatic gene therapy. 1) We have developed a new packaging cell line, ampGPE for retroviral production. LTR-less gag, pol or env genes from Moloney murine leukemia virus were separately inserted into BMGNeo vector. Packaging cell lines containing 20-50 copies of these two kinds of plasmid were obtained. Retrovirus stock for gene-transfer have been produced at a high titer (10(5)-10(6) cfu/ml) and without replication-competent viruses by using ampGPE. 2) Retrovirus-transduced murine CFU-GM have been found to selectively proliferate (5-10 fold/week) in liquid capture with recombinant murine IL-3, human IL-6 and G418 to consequently obtain enough amount of, highly concentrated (70-100%), and gene-transferred murine CFU-GM for gene-delivery system.

Animals↗

[Two cases of hypersensitivity pneumonitis due to contamination of an ultrasonic humidifier].

Two cases of hypersensitivity pneumonitis due to contamination of ultrasonic-humidifier were reported. The first case, a 64-year-old man, developed fever and dyspnea on exertion in January 1986. He was hospitalized for 18 days and received antibiotics for presumptive bacterial pneumonia. Half a day after discharge, those symptoms recurred. On readmission, fine crackles were heard at the left lung base, and chest X-ray film showed ground glass shadows all over the lung fields. Bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) were performed on the next day after readmission. TBLB specimen revealed lymphocyte alveolitis, granulomatous tissue and infiltration of polymorphonuclear neutrophils (PMN) in alveoli. Differential cell count of the BAL fluid showed not only lymphocytosis (38.2%) but also increased PMNs (44.2%). In the second BAL performed 18 days later, the value of PMNs demonstrated a dramatic decrease. Environmental challenge tests revealed that his hypersensitivity pneumonitis was caused by an ultrasonic humidifier in his bed room. Immunological examinations showed positive Arthus type skin reaction and serum precipitin against Aspergillus fumigatus. Inhalation challenge with A. fumigatus produced cough and dyspnea with a decrease of 10 Torr in PaO2. These data suggest that A. fumigatus may be the causative antigen in this case. The second case, a 64-year-old man who had used ultrasonic humidifier in his living room, was admitted for 8 weeks with an illness characterized by cough, low fever and general malaise on 22 January 1987. Examination revealed fine crackles on both lung bases. Chest X-ray film demonstrated diffuse nodular shadows. The TBLB specimen showed lymphocytic alveolitis and bronchiolitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acremonium↗

[A case of diffuse panbronchiolitis complicated by malignant thymoma and Sjögren's syndrome].

A patient with diffuse panbronchiolitis (DPB) complicated by malignant thymoma and Sjögren's syndrome with pseudolymphoma is reported. A 58-year-old woman developed productive cough, dyspnea and sicca in the mouth. Laboratory findings on admission indicated a high titer of cold hemagglutinin, positive of anti-DNA and negative PPD skin test. Chest-X ray revealed diffuse reticulonodular shadows in the lower lung field and anterior mediastinal mass shadow. Pulmonary function studies showed reduction of the vital capacity, forced expiratory volume in one second, DLco and hypoxia (PaO2; 69.1 Torr). Lung biopsy and resection were performed. Histologically infiltration of mononuclear cells and accumulation of foamy cells around respiratory bronchioles and stenosis of terminal bronchioles by granulation tissue was compatible with the diagnosis of DPB and the mediastinal tumor appeared to be a malignant thymoma invading to pericardium. Focal infiltration of lymphocytes was also recognized around the salivary glands (Sjögren's syndrome) and in the alveolar septa (pseudolymphoma). This case of DPB might have been associated with lymphoproliferative disorders.

Bronchiolitis↗

Interleukin-1 beta (IL-1 beta) induces thrombocytosis in mice: possible implication of IL-6.

We administered recombinant human interleukin-1 beta (IL-1 beta), the common mediator of inflammation process, to C57B1/6 male mice (0.5 microgram, every 12 hours over five times) intraperitoneally and consequently induced a remarkable thrombocytosis. Day 1 was designated as the following day of the last injection in the morning. A significant thrombocytosis was observed on days 1 through 5 with a peak on day 2 (162 +/- 9 x 10(4)/mm3) compared with the control mice injected with heated IL-1 beta (101 +/- 11 x 10(4)/mm3). A striking increase in mean size of marrow megakaryocytes was noted on days 1 and 2. The incorporation of 75Se-selenomethionine into circulating platelets as a measure of platelet production was about 2.3 times higher in IL-1 beta-treated mice than in control mice. To determine which factor(s) is responsible for elicited thrombocytosis, the in vitro studies and bioassays for several hematopoietic factors were performed. IL-1 beta by itself did not stimulate megakaryocytopoiesis in vitro, suggesting that the thrombocytosis is attributed to other factor(s) via IL-1 beta stimulation. Serum colony-stimulating factor (CSF) activity after a single IL-1 beta (0.5 microgram) injection, monitored by colony assay with 10% tested serum, peaked at 3 hours. Formed colonies were mostly granulocyte (G) and granulocyte-macrophage (GM)-types, and studies using rabbit anti-mouse GM-CSF serum or using human marrow as target cells showed that the CSF activity of the tested serum consisted of, at least, GM-CSF and G-CSF. Addition of IL-3 concomitantly with the tested serum gave rise to a greater number of megakaryocytic colonies. Serum IL-3, monitored by IL-3-dependent cell line 32D clone 5, and erythropoietin activities were not detected at serum level in IL-1 beta-treated mice. Serum IL-6 assay by IL-6-dependent mouse hybridoma cell line MH-60.BSF2 showed high levels of the tested serum with a peak at 2.5 hours with no detection at 10 hours after the injection. Heated IL-1 beta caused an increase of neither IL-6 nor CSF activities. Our data suggest that the thrombocytosis induced by IL-1 beta is mediated by IL-6 or a combination of IL-6 and other cytokine(s), and that IL-6 may play a regulatory role in platelet production in vivo.

Animals↗

Interleukin-6 enhances murine megakaryocytopoiesis in serum-free culture.

We investigated the effect of interleukin-6 (IL-6) on murine megakaryocytopoiesis in a serum-free culture system. The addition of IL-6 to a culture containing interleukin-3 (IL-3) resulted in a significant increase in the number of megakaryocyte colonies by bone marrow cells of normal mice. The megakaryocytic progenitors that survive exposure to 5-fluorouracil (5-FU) exhibited a more significant response to IL-6 and IL-3. Polyclonal anti-IL-6 antibody neutralized the stimulatory effect of IL-6 on megakaryocyte colony growth supported by IL-3. Delayed addition experiments and replating experiments of blast cell colonies showed that megakaryocytic progenitors are supported by IL-3 in the early stage of the development but require IL-6 for their subsequent proliferation and differentiation. In addition, IL-6 increased the size of megakaryocytes in granulocyte-macrophage-megakaryocyte colonies. The combination of granulocyte colony-stimulating factor or granulocyte-macrophage colony stimulating factor with IL-3 resulted in an increase in the granulocyte-macrophage colony growth of bone marrow cells of 5-FU-treated mice or normal mice, respectively, but had little effect on the enhancement of pure and mixed megakaryocyte colony growth. These results suggest that IL-6 plays an important role in murine megakaryocytopoiesis.

Animals↗

Interleukin 6 perfusion stimulates reconstitution of the immune and hematopoietic systems after 5-fluorouracil treatment.

Effects of interleukin 6 (IL-6) on the functional capacity of the immune and hematopoietic systems in 5-fluorouracil (5-FU)-treated mice were determined. IL-6 (5 x 10(4) units/mouse/day) was administered s.c. for 7 days by implantation of an osmotic pump, since it was demonstrated that a much higher increase in the primary response to sheep RBC was observed by administration of slowly released rather than daily s.c. injection of IL-6. IL-6 perfusion significantly augmented anti-sheep RBC antibody responses depressed by 5-FU (150 mg/kg) treatment. IL-6 also was shown to stimulate hematological recovery in mice treated with 5-FU. Namely, IL-6 perfusion accelerated the recovery of the number of hematopoietic stem cells, granulocyte-macrophage progenitors, and mature neutrophils in the spleen, although IL-6 did not stimulate the recovery of the neutrophil count in blood. Recovery of the platelet count in blood was stimulated by IL-6. Furthermore, it was found that the endogenous IL-6 level in serum increased after 5-FU treatment, which suggests that IL-6 may play some role in the recovery of the immune and hematopoietic systems. Finally, we examined the effect of IL-6 on the survival of mice treated with a higher dosage of 5-FU (300 mg/kg). IL-6 perfusion produced a distinct increase in survival rate at Day 30 (74% versus 28%). It is of note that the number of bacteria (identified as Escherichia coli) cultured from the spleen and the liver decreased in IL-6-perfused mice. This IL-6-induced effect was accompanied by enhancement of an oxidative burst response. Moreover, the anti-E. coli antibody titer in serum was higher in IL-6-perfused mice than in control mice. These results suggest the possible use of IL-6 for stimulating the reconstitution of the immune and hematopoietic systems after chemotherapy treatment.

Animals↗

In vivo effects of recombinant human interleukin-6 in primates: stimulated production of platelets.

In cynomolgus monkeys, twice daily subcutaneous injections of recombinant human interleukin-6 (rhIL-6) at doses of 5 to 80 micrograms/kg/d for 14 consecutive days caused dose-dependent increases in platelet count, usually continuing for more than 1 week after cessation of the injections. The count reached a level approximately twofold or more above the preinjection level even at 5 micrograms/kg/d, and at doses of more than 20 micrograms/kg/d, the increase became biphasic with a higher second peak 3 days after cessation of the injections. Morphologic analysis of the bone marrow after the 7 day-injections with 80 micrograms/kg/d revealed a marked increment in size of megakaryocytes compared with control, indicating the promotion of megakaryocyte maturation. Other changes attributable to the rhIL-6 treatment include dose-dependent loss of body weight, anemia, neutrophilia and monocytosis, elevation of serum C-reactive protein and alpha-1 acid glycoprotein levels, and decrease of serum albumin; all of which returned to normal within 1 week after cessation of the injections and were tolerable at doses of less than 10 micrograms/kg/d. These findings suggest that rhIL-6 may be an effective strategy for the treatment of thrombocytopenia.

Animals↗

Griffonia simplicifolia agglutinin-2-binding glycoprotein as a novel carbohydrate antigen of human colonic carcinoma.

Griffonia simplicifolia agglutinin-2-binding glycoprotein (GBG) in human colonic carcinoma was examined immunochemically and histochemically, GBG was extracted from colonic carcinoma as a serum-type glycoprotein of 160 kilodaltons. GBG was not identical with carcinoembryonic antigen (CEA), since its molecular weight and localization in tissue sections were different from those of CEA. The non-reducing terminals of GBG probably carry N-acetylglucosamine, but not blood group determinants. Furthermore, GBG was released by phosphatidylinositol-specific phospholipase C from cell membrane. GBG was suggested to be anchored to the membrane via linkage to a glycosyl-phosphatidylinositol molecule. Among colonic carcinoma-associated antigens, serum-type glycoproteins having N-acetylglucosamine at non-reducing terminals have not previously been reported. GBG is a novel carbohydrate antigen of human colonic carcinoma.

Adult↗

[Improvement in alveolar macrophage function after therapeutic lung lavage in pulmonary alveolar proteinosis].

Alveolar macrophage (AM) function was investigated in 4 cases of pulmonary alveolar proteinosis (PAP). Therapeutic bronchoalveolar lavage (BAL) with a flexible bronchofiberscope was done 7-13 times during periods of 4-24 weeks. In the initial BAL, the total cell count was only 0.18-0.92 x 10(5)/ml. Also low AM, lymphocytosis and eosinophilia values were noted. The phagocytic activity of AM was only 3-14% and nitroblue tetrazonium (NBT) reduction of AM was under 5% before therapeutic BAL. However, the phagocytic activity was from 25-63% and NBT reduction from 15-35% after therapeutic BAL, AM function with periods of remission of PAP was normal but AM function decreased during relapse and exacerbation of PAP. After therapeutic BAL, two patients have been in remission for three years, one patient with incomplete restoration of AM function relapsed after one year, and one patient without restoration of AM function showed further deterioration after developing pulmonary tuberculosis. These findings indicate that the defect in AM function found in PAP is reversible with therapeutic BAL, and that the severity of PAP is closely associated with AM function.

Adult↗

[Analysis of immunoglobulin G subclasses in chronic respiratory tract infections].

To analyze the immunological aspects of chronic respiratory tract infections, immunoglobulin G (IgG) subclass patterns were investigated in 20 patients with diffuse panbronchiolitis (DPB) and 20 patients with cystic bronchiectasis (CBE). All IgG subclasses were increased in both diseases in comparison to the normal group. Increased levels of IgG1 and IgG2 were recognized more dominantly in DPB, whereas IgG4 level was elevated in CBE. Furthermore, analysis of the ratio of IgG subclass to total IgG showed increase of IgG1 and decrease of IgG2 in both diseases, and increase of IgG4 only in CBE. On the other hand, the increase of IgG1 correlated with infection by P. aeruginosa while increase of IgG4 was recognized in the group of non-P. aeruginosa infections. These results indicate that increased IgG1 and IgG2 levels are common characteristic phenomena in chronic respiratory tract infections such as DPB and CBE, reflecting the pathophysiological aspects based on respiratory tract defense mechanisms against microorganisms, and demonstrated that differences of IgG subclass patterns are observed among DPB and CBE, and also according to causative agents.

Adult↗