Repeated arthralgia associated with granulocyte colony stimulating factor administration.
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Biomedical subjects
Publications and source records attributed to S Takashi.
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We have reported that CD54 on eosinophils is involved in eosinophil degranulation. However, the role of CD54 in eosinophil and neutrophil superoxide production is still uncertain. We assessed the effect of CD54 on eosinophils and neutrophils in recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF)- or phorbol myristate acetate (PMA)-induced superoxide production through CD18. Anti-CD54 monoclonal antibody attenuated leukocyte aggregation and superoxide production of rGM-CSF- or PMA-stimulated neutrophils and PMA-stimulated eosinophils. Anti-CD18 monoclonal antibody or theophylline attenuated superoxide production of eosinophils and neutrophils stimulated by either stimuli. Flow cytometric analysis demonstrated CD54 expression on freshly isolated neutrophils but not on freshly isolated eosinophils. CD54 newly expressed on eosinophils reached its peak expression 30 min after PMA stimulation. The increase in CD18 and CD54 expression on neutrophils caused by rGM-CSF stimulation was partially inhibited by theophylline. These data demonstrated that CD54 and CD18 interaction of eosinophils or neutrophils is involved in superoxide production and that the inhibition of superoxide production by theophylline may be at least partly due to the inhibition of CD54 and CD18.
We reviewed the biological functions of CD4+ eosinophils, which are observed in peripheral blood, sputum and bronchoalveolar lavage fluid of various diseases. We have shown that CD4 molecules on human eosinophils are induced by tumor necrosis factor-alpha (TNF-alpha) stimulation. Interleukin-16 (IL-16) has been reported to bind a natural soluble ligand for the CD4 molecule. We reported that TNF-alpha-stimulated eosinophils migrate in a time- and dose-dependent manner against IL-16. Theophylline and dexamethasone significantly inhibited CD4 expression. Theophylline inhibited CD4+ eosinophil chemotaxis, but dexamethasone did not. Theophylline may prevent airway inflammation by downregulating the expression of CD4 molecule and CD4+ eosinophil migration. However, dexamethasone may inhibit airway inflammation through the downregulation of CD4 expression.
We encountered two cases of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). The first was a case of idiopathic interstitial pneumonia diagnosed in a 73-year-old man since 1998. He was admitted to our hospital because of renal failure and anemia. The serum level of p-ANCA on admission was 264 EU, and specimens obtained by percutaneous renal biopsy showed crescentic glomerulonephritis and vasculitis due to p-ANCA. He was treated with prednisolone pulse therapy and prednisolone (PSL), however interstitial pneumonia occurred during PSL tapering. We treated him for pulmonary fibrosis with plasmapheresis, methylprednisolone (mPSL) and cyclophosphamide (CPA), which suppressed the progress of the interstitial pneumonia. The second case was one of massive pulmonary hemorrhage in a 68-year-old man who was admitted to our hospital. Physical examination revealed anemia: the laboratory data, renal failure; and the serum level of p-ANCA was elevated to 611 EU. The specimens obtained by percutaneous renal biopsy showed crescentic glomerulonephritis and vasculitis. The renal failure was not improved by PSL, but, together with the inflammation, responded to the combination of PSL and CPA. However, both patients died of serious infection. They were regarded as compromised patients because of the therapy mentioned above. No standard therapy has been established against p-ANCA positive pulmonary disease with renal failure. The treatment should control the progression of interstitial pneumonitis and pulmonary hemorrhage. It is important to consider the possibility of serious infection.
A 74-year-old woman was admitted to our hospital because of right chest pain. The chest radiograph showed right hilar pulmonary artery dilatation. A mass exhibiting low intensity in T1-weighted images and high intensity in T2-weighted images was disclosed in the right pulmonary artery. Because of its clinical course and the MRI findings, the mass was thought to be tumorous tissue, and so pneumonectomy was performed. Leiomyosarcoma was diagnosed from the histological findings. Primary artery sarcoma is rare and the prognosis is considered to be extremely poor. The patient was successfully treated and had a good clinical outcome.
A 76-year-old man with postoperative renal cell carcinoma accompanied by multiple lung metastasis was being treated with recombinant interferon-alpha. After administration of 3 MU/day on 3 days/week for 1 month, he complained of headache and tinnitus. During continuous treatment for 3 months, he complained of appetite loss, low-grade fever and dyspnea. He was then referred to our Department of Internal Medicine. Electrocardiography indicated a complete A-V block, and chest radiography (CXR) showed a reticular shadow in both lower lung fields and bilateral pleural effusion. Chest computed tomography (CT) indicated subpleural emphysematous changes, multiple nodules, consolidation shadow with ground glass opacity in both lower lobes, and bilateral pleural effusion. The findings in the bronchoalveolar lavage (BAL) fluid included increases in the numbers of lymphocytes and eosinophils. We reached a diagnosis of interferon-alpha-induced pneumonitis on the basis of the patient's clinical course, and the CXR, chest CT and BAL fluid findings. Treatment with methylprednisolone pulse therapy for 3 days and then administration of prednisolone for 1 month resulted in marked improvement in the complete A-V block and interstitial pneumonitis. At day 7 after discontinuation of prednisolone, the serum level of C-reactive protein increased, and CXR showed bilateral pleural effusion. We therefore believe that the pleural effusion was probably also induced by interferon-alpha. Interferon is an effective drug for chronic hepatitis C and malignant diseases. Many complications have been reported during interferon therapy. However, although these complications, such as interstitial pneumonitis, complete A-V block and pleural effusion, have rarely been reported, careful attention is required during interferon therapy in case any appear.
BACKGROUND: The pathophysiology of eosinophilia and hyper-IgE is not fully elucidated yet. OBJECTIVE: To clarify the pathophysiology of a patient with remarkable eosinophilia and hyper IgE, we examined cytokine levels in serum, surface antigens of peripheral blood eosinophils and IgE production in vitro. RESULTS: Concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), and granulocyte/macrophage-colony stimulating factor (GM-CSF) in the serum were 21 pg/mL, <15 pg/mL, <15 pg/mL, 8 pg/mL, and <5 pg/mL pg/mL, respectively. Newly expressed surface antigens CD4, CD25, CD69, and HLA-DR, but not CD54, were observed on peripheral blood eosinophils. Extremely high levels of IgE secretion was found in the patient's mononuclear cells without stimuli; this was not enhanced by IL-4 or IL-4 plus anti-CD40 monoclonal antibody stimulation. Furthermore, highly purified B cells spontaneously produced large amounts of IgE and the production was not enhanced in addition of his T cells. CONCLUSION: The eosinophils were activated, and the B cells spontaneously produced IgE independently of T cells or cytokines, suggesting that intrinsic abnormality of B cells leading to dysregulated production of IgE in this disease.
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We report a case of schwannoma asymptomatic for 9 years, derived from the left vagus nerve in the middle mediastinum. This spindle-shaped tumor caused paralysis of the left recurrent nerve as an initial clinical manifestation with cough. T2-weighted magnetic resonance imaging (MRI) showed a neurogenic tumor with a characteristic target appearance and with constituents of different intensities: mucinous material in the peripheral zone and solitary tissue in the central zone. But, this different intensity is not directly reflected by the histopathologic features of Antoni types A and B. These findings suggest that MRI is useful for determining the parent nerve of a neurogenic tumor and is helpful for the diagnosis.
A 51-year-old female was admitted to Nagano Matsushiro General Hospital because of fever, cough and dyspnea on exertion. Her laboratory data revealed leukocytosis with hypereosinophilia, a high erythrocyte sedimentation rate and c-reactive protein. Chest radiography revealed an infiltration shadow with a cavity in the right upper lobe. A lung abscess was diagnosed and antibiotics were administered. Laboratory results showed improvement, but chest radiography continued to show cavities. She was admitted to our hospital because of fever, left pleural effusion and progression of cavities on chest radiographs. She showed no abnormalities of the upper airway or kidney, and was negative for c-antineutrophil cytoplasmic antibody (c-ANCA). Because a positive c-ANCA was seen on day 8 of hospitalization, L-type limited Wegener granulomatosis (WG) was diagnosed according to Gross et al. Prednisolone (PSL) was administered, which improved the anemia, eosinophilia and the cavities. On day 7 of PSL administration, of the left pneumothorax occurred as a complication caused by perforation of the left chest cavity, but her clinical course was good after a cavernectomy was performed. Some studies have reported that limited WG shows a negative c-ANCA, and that antibiotic therapy improves inflammation. The L-type of limited WG revealed a low-grade positive ratio and titer of c-ANCA. Moreover, L-type limited WG responds well to therapy. We therefore selected PSL administration only against L-type limited WG. We have reported L-type limited WG with eosinophilia and the negative effects of c-ANCA at an early clinical stage.
BACKGROUND: L-selectin (CD62L) and Mac-1 (CD11b/CD18) play a crucial role in the infiltration of eosinophils. However, changes in CD62L and CD11b expression on eosinophils after stimulation with cytokines were little studied. METHODS: Eosinophils in peripheral blood of healthy volunteers were purified and cultured with interleukin-5 (IL-5), granulocyte/macrophage colony-stimulating factor (GM-CSF) or interferon-gamma (IFN-gamma). After up to 24 h incubation, CD62L and CD11b expression were examined using flow cytometry. The effects of dexamethasone (Dex), cycloheximide (CHX) or theophylline on CD62L expression on IFN-gamma-stimulated eosinophils were also studied. RESULTS: IL-5 or GM-CSF downregulated CD62L and upregulated CD11b expression on eosinophils after 30 min stimulation. Conversely, IFN-gamma upregulated CD62L after 12 h stimulation in a time- and dose-dependent manner, and had no effect on CD11b expression. Dex, CHX or theophylline dose-dependently decreased CD62L expression on IFN-gamma-stimulated eosinophils. CONCLUSIONS: IFN-gamma is a particular cytokine which can increase CD62L expression on circulating or infiltrated human eosinophils. It is suggested that protein synthesis and intracellular cAMP participate in the increase in L-selectin expression on IFN-gamma-stimulated eosinophils.
We reviewed 98 children (133 hips) with developmental dysplasia of the hip who underwent arthrography immediately after closed reduction by overhead traction. We followed the patients to skeletal maturity to investigate whether soft-tissue interposition influences acetabular development and avascular necrosis over the long term. The shape of the limbus and the thickness of the soft-tissue interposition at the acetabular floor, as shown on arthrograms at the time of reduction, were not directly related to the final radiological results or to the incidence of avascular necrosis. Even if marked soft-tissue interposition was found on the initial arthrogram, spontaneous disappearance was noted in 71% up to the age of five years. The final radiological results showed no difference between those in which the interposition disappeared and those with none at the time of closed reduction. However, the requirement for secondary surgery at the age of five years was significantly higher in those with more than 3.5 mm of soft-tissue interposition. In the no-disappearance group (group C) further operation was necessary in 100% and the results were significantly worse at maturity according to Severin's classification. We suggest that the indications for open reduction should not be based solely on the arthrographic findings at the time of closed reduction.
We examined the effect of hyperbaric oxygenation (HBO2) treatment on lengthened callus. The left tibias of 18 immature rabbits were progressively lengthened 14 mm by external fixator. They were divided into three groups of six each. The early HBO2 treatment group was exposed to HBO2 (3 atm abs, 2 h x day(-1)) once a day for the waiting period and the elongation period (17 days), the late HBO2 treatment group was exposed to HBO2 (same condition) for 17 days after the elongation period, and the control group received no HBO2 treatment. The radiographic examinations showed a tendency toward rapid callus formation in the early HBO2 treatment group. The percentage of bone mineral density evaluated using dual-energy x-ray absorptiometry in the early HBO2 group was significantly higher than that in the control group for 4 wk after the elongation period. These results suggest that HBO2 in the waiting and elongation periods enhances lengthened callus formation.
A 42-year-old man was admitted to our hospital because of dyspnea on exertion, skin eruptions on the face and extremities, and interstitial shadows mainly in the lower fields of both lungs. Characteristic skin lesions and skin biopsy findings without muscle symptoms or elevated CPK resulted in a diagnosis of amyopathic dermatomyositis (ADM). Thoracoscopic lung biopsy specimens disclosed BOOP-type interstitial pneumonia. Oral prednisolone (PSL) was initiated at 60 mg/day and gradually tapered. However, because his respiratory symptoms and laboratory findings deteriorated, the patient underwent 5 courses of cyclophosphamide (CPA) pulse therapy. Following improvement of his subjective symptoms, arterial blood gas data, and respiratory functions, the patient was discharged and placed on oral PSL and CPA. CPA was discontinued 18 months later. The patient has continued to receive PSL (5 mg/day) and has been in good condition for 3 years. Though the prognosis for interstitial pneumonia associated with ADM is reported to be poor, our patient represented a rare case of BOOP-type interstitial pneumonia brought into remission by CPA pulse therapy.
Between 1996 and 1998, we treated 6 patients with unresectable and advanced thymic cancer (stages IVa and IVb). All received 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously (i.v.) on day 1,0.6 mg/m2 of vincristine i.v. on day 3, and 700 mg/m2 of cyclophosphamide i.v. on day 4; ADOC regimen, respectively at 3-4 week intervals. Four patients obtained a partial response (PR) after ADOC chemotherapy and the overall clinical response rate was 67%. No life-threatening side effects were noted. In 2 patients, cisplatin plus VP-16 chemotherapy failed to demonstrate any benefits prior to the ADOC regimen. Radiotherapy was initiated after the achievement of PR in the other 2 patients. ADOC chemotherapy appears to be an effective treatment for thymic cancer.
BACKGROUND: Kimura's disease is a rare but distinctive eosinophilic inflammatory disorder of unknown etiology; few reported case studies have focused on the immunopathologic background of this unique disease. OBJECTIVE: To define better the immunopathogenetic features of Kimura's disease, we attempted to quantitatively analyze values of cytokines and soluble interleukin-2 receptor (sIL-2R) in peripheral blood (PB), as well as perform surface immunophenotypic analysis of eosinophils from a Japanese patient with chronic relapsing Kimura's disease. RESULTS: Granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha) and sIL-2R were elevated, and newly expressed antigens on eosinophils CD4, CD25, and HLA-DR were found to be involved in the pathophysiology of this disorder. CONCLUSIONS: Kimura's disease may be a disease in which activated lymphocytes release cytokines, and these released cytokines, such as GM-CSF and TNF-alpha cause eosinophil activation. These processes may be related to the pathogenesis of this disorder.
BACKGROUND: Acute eosinophilic pneumonia (AEP) is a rare disease with unknown etiology. To examine pathophysiology of AEP we measured the cell number of eosinophils and eosinophil active cytokines in the peripheral blood and bronchoalveolar lavage fluid (BALF) of AEP patients and compared the levels with those measured in chronic eosinophilic pneumonia (CEP) patients. METHODS: Cell number of eosinophils in peripheral blood and BALF from patients with AEP (n = 3) and CEP (n = 3) were measured. Eosinophil active cytokines in serum and BALF from the patients were measured using ELISA. RESULTS: Eosinophil cell number in peripheral blood was 274-1,377/mm3 in AEP and 526-2,500/mm3 in CEP. The percentages of BALF eosinophils were high in AEP and CEP. Eosinophilia disappeared after methylprednisolone pulse therapy (1 g for 3 days) in AEP, however the cell number of eosinophils gradually increased after methylprednisolone pulse therapy and then spontaneously decreased to within normal range without any further medication. The concentrations of IL-5 in AEP were very high in serum and in BALF, however the concentrations in CEP were low in serum and BALF. CONCLUSION: AEP is a disease in which eosinophil active cytokine IL-5 is predominantly involved; CEP is not. The factors involving eosinophil infiltration to inflammatory loci differ between AEP and CEP.
A 62-year-old female with diffuse pulmonary amyloidosis developed abnormal radiographic findings while under observation for hyperimmunoglobulinemia over a ten-year period. Serum immunoglobulin G (IgG) was elevated (4,620 mg/dl), and associated with monoclonal gammopathy (M protein) of the kappa type, but no evident abnormalities were apparent in bone marrow. Chest radiograph and computed tomography showed a diffuse reticulonodular shadow in the bilateral lung. Thoracoscopic lung biopsy specimen revealed depositions of amyloid in the bronchus and pulmonary vessel. We emphasize that diffuse pulmonary amyloidosis should be considered a possible diagnosis in the presence of monoclonal immunoglobulin.