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Biomedical subjects

Ryoji Ito

Publications and source records attributed to Ryoji Ito.

14 recordsLinked to original sources

Development of human-human hybridoma from anti-Her-2 peptide-producing B cells in immunized NOG mouse.

OBJECTIVE: Numerous monoclonal antibodies have been developed for the purpose of medical treatments, including cancer treatment. For clinical application, the most useful are human-derived antibodies. In this study, we tried to prepare designed antigen-specific antibodies of completely human origin using immunodeficient mouse. METHODS: Nonobese diabetic/severe combined immunodeficient/IL-2 receptor gamma null mouse (NOG) mouse was used to reconstitute the human immune system with umbilical cord blood hematopoietic stem cells (CB-NOG mouse) and to prepare human-derived Her-2-epitope-specific antibodies. Hybridoma lines were prepared by fusing the human myeloma cell line Karpas707H. RESULTS: Serum of immunized NOG mouse contained human-derived immunoglobulin M (IgM) antibodies specific for a short peptide sequence of 20 amino acids, including the epitope peptide of apoptotic Her-2 antibody CH401. Hybridoma lines were successfully prepared with spleen B cells obtained from the immunized CB-NOG mouse. One of these cell lines produced human IgM against the epitope peptide that can recognize surface Her-2 molecule. CONCLUSION: We could produce human-derived IgM antibody against Her-2 epitope peptide in CB-NOG mouse, succeeding in generation of human hybridoma-secreting IgM against a given peptide.

Animals↗

Effect of inhaled bronchodilators on air trapping in patients with stable asthma.

Air trapping is frequently observed during high-resolution computed tomography (HRCT) of patients with asthma, but whether the condition is reversible has not been thoroughly investigated. The aim of the present study was to evaluate reversibility of air trapping in response to bronchodilator. Ten never-smokers with stable asthma enrolled in the study. Spirometry and HRCT were performed before and after bronchodilator inhalation. Air trapping remained unchanged, although significant reversibility of FEV(1) was observed. Air trapping scores correlated significantly with airway wall thickness. These observations suggest that air trapping is irreversible and that it represents structural remodeling of small airways in patients with stable asthma.

Administration, Inhalation↗

Metastatic renal cell carcinoma presenting as multiple pleural tumours.

A 66-year-old man was admitted with dyspnoea. Chest X-ray and chest computed tomography (CT) demonstrated a left-sided pleural effusion and multiple tumours, suggesting malignant mesothelioma in the left pleural space, but there were no pulmonary lesions. However, abdominal CT revealed a right renal tumour. An ultrasonography-guided needle biopsy of the pleural mass provided evidence of metastatic renal cell carcinoma (RCC). The pleural lesions dramatically decreased in size following right radical nephrectomy and subsequent interferon-alpha treatment. While the thorax is a frequently affected site of RCC, sole pleural metastases are rare and are often secondary to lung involvement. Batson's plexus, a network of vertebral valve-less veins with multiple connections, is likely responsible for the contralateral pleural metastases of RCC.

Aged↗

Two cases of reversible posterior leukoencephalopathy syndrome, one with and the other without pre-eclampsia.

Two cases of reversible posterior leukoencephalopathy syndrome (RPLS) are reported. One was a 26-year-old woman, who had pre-eclampsia and developed cortical blindness and subsequent eclampsia at 28 weeks' gestation. The other was a 27-year-old woman, who had no pre-eclampsia and developed loss of consciousness and subsequent systemic convulsion at 36 weeks' gestation. On brain magnetic resonance imaging, they both had high signal intensity on T2-weighted and fluid-attenuated inversion recovery images, and normal signal intensity on diffusion-weighted image of the posterior lobe, which almost disappeared with the amelioration of clinical symptoms thereafter. RPLS is considered to be the result of vasogenic brain edema caused by hypertension. Two hypotheses are conceived to explain the emergence of RPLS without hypertension. The first suggests that an immunotolerant condition such as pregnancy can easily cause vasogenic edema without the elevation of blood pressure. The second suggests that hypertension exists but cannot be detected because it is extremely acute and transient.

Adult↗

Hemoperitoneum secondary to spontaneous rupture of hepatic metastasis from lung cancer.

We describe a rare case of hemoperitoneum secondary to spontaneous rupture of hepatic metastasis from lung cancer. A 72-year-old man with non-small cell lung cancer was admitted to our hospital with sudden onset of right upper abdominal pain and hypovolemic shock. Laboratory tests showed severe anemia. Abdominal contrast-enhanced computed tomography revealed massive ascites and multiple liver metastases. Rupture of a metastatic liver tumor was suspected. Only palliative therapy was performed. The patient's general condition gradually worsened, and he died 2 months after admission. Autopsy examination revealed hemoperitoneum due to a ruptured metastatic liver tumor originating from pulmonary squamous cell carcinoma.

Aged↗

[A case of small cell lung cancer with intramedullary spinal cord metastasis].

An 83-year-old man was admitted with paraplegia and loss of all sensation below the level of umbilicus, with bowel and bladder dysfunction. Stage IV small cell lung cancer had been diagnosed two years ago and had received several courses of chemotherapies. A magnetic resonance imaging revealed an enhanced mass in the intramedullary spinal cord at the level of Th10-L1. Metastatic spinal tumor was diagnosed by clinical and radiological examinations. This is a rare case of small cell lung cancer with intramedullary spinal cord metastasis which caused various neurological symptoms.

Aged↗

Clarithromycin-induced eosinophilic pneumonia.

Clarithromycin (CAM) has been widely used for the treatment of respiratory infection. Macrolides are generally well tolerated and their adverse reactions are rare. An 80-year-old woman with nontuberculous mycobacterium infection was treated with combined chemotherapy, including isoniazid, rifampicin, and ethambutol. She developed a fever and peripheral blood eosinophilia, and new subpleural consolidations were observed on chest radiography three days after add-on therapy with CAM. The symptoms and clinical findings improved with the withdrawal of CAM. Histopathologic examinations confirmed the diagnosis of eosinophilic pneumonia. This is the first report of CAM-induced eosinophilic pneumonia.

Aged↗

[A case of interstitial pneumonia caused by gosha-jinki-gan].

A 74-year-old woman was admitted to the hospital of Ehime University School of Medicine because of slight fever, dry cough and dyspnea on exertion. Chest X-ray films on admission showed diffuse infiltrations in both lungs. Drug-induced pneumonia due to the herbal medicine Gosha-jinki-gan was suspected, as Gosha-jinki-gan had been administered for 5 months for the treatment of a right knee pain. Her symptoms and the X-ray abnormality improved after cessation of administration. The lymphocyte stimulation test against Gosha-jinki-gan was positive. To the best of our knowledge, this is the first case of interstitial pneumonia caused by Gosha-jinki-gan.

Aged↗

[A case of primary adenocarcinoma of the trachea].

Primary adenocarcinoma of the trachea is rare. We present a case that was successfully treated with radiotherapy followed by surgical resection. A 66-year-old man was admitted to our hospital because of cough, sputum and dyspnea. A chest CT film showed a tracheal tumor, and transtracheal biopsy specimen showed well-differentiated papillary adenocarcinoma. Other examinations excluded the diagnosis of metastatic adenocarcinoma from other organs. Since stenosis of the trachea was rapidly progressive, a tracheal stent was inserted to alleviate the obstruction. After radiotherapy, the tumor size decreased, after which surgical resection was performed. No recurrence had been observed 26 months after the operation.

Adenocarcinoma↗

Requirement of transcription factor AML1 in proliferation of developing thymocytes.

Although the transcription factor AML1/Runx1 is known to be essential for definitive hematopoiesis, its role in T cell differentiation is not well understood. In this study, we investigated the functions of AML1 in the early stage of thymocyte differentiation. For this, we crossed AML1 dominant interfering form (Runt)-transgenic mice with TCR-transgenic mice, and demonstrated the decrease of CD4+8+ (DP) thymocyte cell number although their proportion was not reduced. Reaggregation culture system for thymocytes of (RuntxTCR) double transgenic mice, in which the rate of de novo transition from DN cells to the DP stage can be estimated, showed that the cell division during the DN-to-DP transition is impaired without significant cell death. These results indicate that AML1 is involved in thymocyte differentiation by controlling cell proliferation.

Animals↗

Functional CD5+ B cells develop predominantly in the spleen of NOD/SCID/gammac(null) (NOG) mice transplanted either with human umbilical cord blood, bone marrow, or mobilized peripheral blood CD34+ cells.

OBJECTIVE: Human CD5+ B cells are the major B cell subset in fetal spleen and umbilical cord blood (CB), and their number gradually diminishes in both spleen and peripheral blood from infancy through childhood while conventional B cells increase. In this study, we investigated whether CD5+ cells differentiate from adult hematopoietic stem cells (HSCs) as well as fetal ones in immunodeficient mice. METHODS: In our system, NOD/SCID/gammac(null) (NOG) mice were transplanted with CD34+ cells from CB (hCB model), adult bone marrow (hBM model), and mobilized peripheral blood (hMPB model). RESULTS: In these model mice, a high proportion of CD19+IgM+CD5+ mature B cells appeared in the spleen, regardless of the CD34+ cell origin, 4 to 8 weeks after transplantation, while the majority were CD19+IgM-CD5- immature B cells in BM. The CD19+CD5- BM cells showed to express CD5 after the coculture with NOG spleen cells. In the sera of immunized hCB model mice with DNP-KLH, antigen-specific IgM but not IgG was enhanced. CONCLUSION: Our results show that adult CD34+ cells develop into functional CD5+ B cells in NOG spleen as much as fetal CD34+ cells do.

Animals↗

[Successful treatment of bronchiolitis obliterans organizing pneumonia with cyclosporin and steroids].

A 71-year-old woman with fever and dry cough was admitted to our hospital. Chest computed tomography, bronchoalveolar lavage and transbronchial lung biopsy were performed, and bronchiolitis obliterans organizing pneumonia (BOOP) was diagnosed. The patient was treated with corticosteroid, and marked improvement was noted. However, when the dosage was tapered, the BOOP recurred. We increased the dosage of corticosteroid and also put the patient on a daily regimen of cyclosporin. The cyclosporin was administered orally, and was effective, so that we could gradually decrease the dosage of corticosteroid. We concluded that cyclosporin may be useful in the treatment of refractory BOOP.

Aged↗

Humidifier lung: possible contribution of endotoxin-induced lung injury.

A 56-year-old man was admitted with cough, fever, myalgia, and arthralgia. Chest computed tomography demonstrated bilateral diffuse ground-glass opacities predominantly in the upper lungs. Subpleural non-segmental consolidation was observed in the late phase. Hypersensitivity pneumonitis was suspected, and an environmental provocation test with the incidental use of a home ultrasonic humidifier was positive. Unlike typical hypersensitivity pneumonitis, serum KL-6 levels were normal. Although several microorganisms were isolated from the humidifier water, there was no evidence for immune sensitization. We detected high amounts of endotoxin in the humidifier water, which may have contributed to the lung injury of this patient.

Alveolitis, Extrinsic Allergic↗

Successful treatment of obstructive sleep apnea syndrome improves autonomic nervous system dysfunction.

Autonomic nervous system (ANS) dysfunction may be implicated in the subsequent development of cardiovascular disease in patients with obstructive sleep apnea syndrome (OSAS). To confirm the relation between OSAS and ANS dysfunction, we prospectively investigated ANS function in 7 patients with moderate or severe OSAS; 7 healthy age-matched volunteers were for control. We also studied ANS function before and after treatment in the patients with OSAS to evaluate the effect of OSAS treatment on ANS dysfunction. The body mass index of patients with OSAS was 32.2 (27.4-45) (median [range]) kg/m2. The patients were treated by nasal continuous positive airway pressure (n = 5) or uvulopalatopharyngoplasty (n = 2). The apnea/hypopnea index decreased markedly from 42.1 (30.6-77.2) events/hr of sleep before treatment to 2.3 (1.4-3.8) after treatment. To evaluate ANS function, the coefficient of variation of the RR interval (CV-RR) and corrected QT (QTc) interval on the electrocardiogram at rest and the heart rate (HR) responses to blood pressure (BP) changes during the Valsalva maneuver were studied. Baseline HR of OSAS patients was significantly higher than that of the control subjects (p < .05). The Valsalva ratio (VR), baroreflex sensitivity (BRS), and CV-RR values in patients with OSAS were significantly lower than those of the control subjects (all, p < .005). However, there were no significant differences in systolic and diastolic BP or QTc intervals. After treatment, VR, BRS, and CV-RR values increased significantly compared with those before treatment in patients with OSAS (all, p < .05). There were no significant differences in systolic and diastolic BP, HR, or QTc intervals measured before and after treatment. These results suggest that impaired ANS function is present in patients with OSAS and can be improved by successful treatment of OSAS.

Adult↗