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Biomedical subjects

Hideki Nakano

Publications and source records attributed to Hideki Nakano.

31 records · Page 2Linked to original sources

[A case of adenocarcinoma of the lung presenting symptoms of choroidal metastasis as the initial clinical manifestation].

A 51-year-old woman was referred to our hospital with a complaint of disturbance in vision. Ophthalmologic examination revealed multiple choroidal tumors. High-resolution CT showed a nodular shadow in the left lower lobe. Transbronchial biopsy and right supraclavicular lymph node biopsy specimens showed a poorly-differentiated adenocarcinoma. We concluded that the choroidal tumors had metastasized from the lung. Combined chemotherapy (CDDP + CPT-11) followed by irradiation of both eyes and brain were performed. Nevertheless, she died 6 months after the initial presentation. It is important to notice ophthalmologic symptoms because lung cancer may metastasize to the choroids.

Adenocarcinoma↗

[Cyclosporin treatment of interstitial pneumonia and monitoring of serum concentration].

Recently, cyclosporin has been reported to be a promising drug for the treatment of interstitial pneumonia. Monitoring of the serum cyclosporin concentration is important for the safety and efficacy of treatment. We measured the concentrations of this drug just before (C0) and 2 hours after (C2) administration, and the area under the concentration-time curve from the start of administration for 5 hours (AUC 0-5) in 58 patients. We found that C2 has the strongest correlation with AUC 0-5, which indicates the efficacy of cyclosporin. In 11 cases of interstitial pneumonia, 5 showed deterioration despite cyclosporin treatment. Three of those 5 cases had low C2 and AUC 0-5 levels, indicating that they were low absorbers and slow absorbers, which may be associated with a poor response. Therefore, the monitoring of the cyclosporin concentration is important especially in progressive cases of interstitial pneumonia that deteriorate despite cyclosporin treatment.

Aged↗

Increased regional cerebral blood flow but normal distribution of GABAA receptor in the visual cortex of subjects with early-onset blindness.

Before the completion of visual development, visual deprivation impairs synaptic elimination in the visual cortex. The purpose of this study was to determine whether the distribution of central benzodiazepine receptor (BZR) is also altered in the visual cortex in subjects with early-onset blindness. Positron emission tomography was carried out with [(15)O]water and [(11)C]flumazenil on six blind subjects and seven sighted controls at rest. We found that the CBF was significantly higher in the visual cortex for the early-onset blind subjects than for the sighted control subjects. However, there was no significant difference in the BZR distribution in the visual cortex for the subject with early-onset blindness than for the sighted control subjects. These results demonstrated that early visual deprivation does not affect the distribution of GABA(A) receptors in the visual cortex with the sensitivity of our measurements. Synaptic elimination may be independent of visual experience in the GABAergic system of the human visual cortex during visual development.

Adult↗

Distinct antigen trafficking from skin in the steady and active states.

In antigen trafficking from the skin, it has been postulated that Langerhans cells/dendritic cells are activated after capturing exogenous antigens, up-regulate the expression of the chemokine receptor, CCR7, and migrate into lymphoid organs in response to the signaling of a chemokine, CCL21, which is expressed in lymphatic vessels and T cell zone stromal cells. Here we demonstrate that there is a distinct pathway of antigen trafficking from skin in the steady state that is independent of CCL21-CCR7 signaling. Employing melanin granules as an endogenous traceable antigen, we developed a system for visualizing antigen trafficking using mice with melanocytosis in the skin. We found the abrogation of antigen trafficking into regional lymph nodes (LN) in CCL21-Ser-deficient paucity of lymph node T cells (plt) mice in the active state induced by lipopolysaccharide injection, corresponding with previous reports, but normal accumulation of antigen in regional LN under steady-state conditions. These findings suggest that self-antigen is trafficking constitutively using pathway(s) other than that of the active state and the constitutive trafficking might regulate self-reactivity of the immune system.

Animals↗

Antiviral immune responses in the absence of organized lymphoid T cell zones in plt/plt mice.

The paucity of lymph node (LN) T cells (plt) mutation in mice results in strongly reduced T cell numbers in LNs and homing defects of both dendritic cells (DCs) and naive T cells. In this study, we investigated the functional significance of the plt phenotype for the generation of antiviral immune responses against cytopathic and noncytopathic viruses. We found that DC-CD8(+) T cell contacts and the initial priming of virus-specific T cells in plt/plt mice occurred mainly in the marginal zone of the spleen and in the superficial cortex of LNs. The magnitude of the initial response and the maintenance of protective memory responses in plt/plt mice was only slightly reduced compared with plt/+ controls. Furthermore, plt/plt mice mounted rapid neutralizing antiviral B cell responses and displayed normal Ig class switch. Our data indicate that the defective homing of DCs and naive T cells resulting from the plt/plt mutation results in a small, but not significant, effect on the induction of protective antiviral T and B cell immunity. Overall, we conclude that the spatial organization of secondary lymphoid T cell zones via the CCR7-CC chemokine ligand 19/CC chemokine ligand 21 pathway is not an absolute requirement for the initial priming and the maintenance of protective antiviral T and B cell responses.

Animals↗

Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position.

B lymphocytes re-circulate between B-cell-rich compartments (follicles or B zones) in secondary lymphoid organs, surveying for antigen. After antigen binding, B cells move to the boundary of B and T zones to interact with T-helper cells. Despite the importance of B--T-cell interactions for the induction of antibody responses, the mechanism causing B-cell movement to the T zone has not been defined. Here we show that antigen-engaged B cells have increased expression of CCR7, the receptor for the T-zone chemokines CCL19 and CCL21, and that they exhibit increased responsiveness to both chemoattractants. In mice lacking lymphoid CCL19 and CCL21 chemokines, or with B cells that lack CCR7, antigen engagement fails to cause movement to the T zone. Using retroviral-mediated gene transfer we demonstrate that increased expression of CCR7 is sufficient to direct B cells to the T zone. Reciprocally, overexpression of CXCR5, the receptor for the B-zone chemokine CXCL13, is sufficient to overcome antigen-induced B-cell movement to the T zone. These findings define the mechanism of B-cell relocalization in response to antigen, and establish that cell position in vivo can be determined by the balance of responsiveness to chemoattractants made in separate but adjacent zones.

Animals↗

Irradiation up-regulates CD80 expression through induction of tumour necrosis factor-alpha and CD40 ligand expression on B lymphoma cells.

Previously, we reported that 100 Gy X-ray irradiation followed by 24 hr incubation up-regulates CD80 expression in murine B lymphoma cells, A20-2J. In the present study, we analysed the underlying mechanisms of such up-regulation using A20-HL cells derived from A20-2J cells. Irradiation of A20-HL cells with 100 Gy enhanced CD80 expression. Incubation of untreated A20-HL cells with those 100 Gy irradiated induced up-regulation of CD80 expression. Irradiation of A20-HL cells also up-regulated the expression of tumour necrosis factor-alpha (TNF-alpha) and CD40 ligand (CD40L), and the amount of immunoprecipitable TNF-alpha and CD40L in cell lysates. The addition of anti-TNF-alpha or anti-CD40L monoclonal antibody (mAb) to the incubation of irradiated A20-HL cells partially inhibited up-regulation of CD80 expression, and the addition of both antibodies together almost completely inhibited the up-regulation, suggesting that irradiation up-regulated the CD80 expression through the induction of TNF-alpha and CD40L expression. Irradiation also increased the accumulation of CD80, TNF-alpha and CD40L mRNA. n-tosyl-l-phenylalanine chloromethyl ketone (TPCK), a nuclear factor (NF)-kappaB inhibitor, markedly decreased irradiation-induced accumulation of CD80 mRNA and CD80 expression. FK506, a calcineurin inhibitor, and nifedipine, a calcium channel inhibitor, inhibited not only the expression of TNF-alpha and CD40L, but also the up-regulation of CD80 on irradiated A20-HL cells. These results strongly suggested that irradiation induced TNF-alpha and CD40L expression, which then up-regulated CD80 mRNA and CD80 expression through activation of NF-kappaB transcription factor in A20-HL cells.

Animals↗

[Eosinophilic pleural effusion associated with dantrolene administration].

A 42-year old man was admitted to our hospital for evaluation of pleural effusion in the right hemithorax. He had been treated for spastic paraplegia with dantrolene sodium for 28 months. The pleural fluid consisted of sterile exudates with a very high eosinophil count, and peripheral blood eosinophilia was noted. Thoracoscopy revealed no apparent abnormalities and a pleural biopsy specimen showed only non-specific inflammation. Two weeks after discontinuing dantrolene therapy, the pleural effusion disappeared. The toxicity of dantrolene in patients with pleural effusion must be taken into consideration when long-term dantrolene therapy is given.

Adult↗

[Secondary pulmonary alveolar proteinosis associated with myelodysplastic syndrome].

A 51-year-old man with myelodysplastic syndrome (MDS) was admitted to our hospital because of dyspnea on exertion in December 1999. Chest radiography showed ground-glass shadows in the middle and lower fields of both lungs, and chest computed tomography revealed a typical "crazy paving appearance". The bronchoalveolar lavage fluid was milky in appearance, and so secondary pulmonary alveolar proteinosis associated with MDS was diagnosed. Because there was no need to treat his MDS, we twice performed whole-lung lavage under general anesthesia in January and February 2000. The treatments were effective, and his abnormal chest radiography findings, laboratory data and pulmonary function were normalized. This was a rare case of secondary pulmonary alveolar proteinosis associated with MDS successfully treated with whole-lung lavage.

Bronchoalveolar Lavage↗

[Clinical analysis of chronic hypersensitivity pneumonitis].

Chronic hypersensitivity pneumonitis (CHP) has a poor prognosis because of the difficulties in its diagnosis and treatment. Recently, we have encountered six cases of CHP (4 patients with the home-related type, a patient with bird fancier's lung, and one with flour-induced CHP), and we examined the clinical characteristics of these cases. Environmental provocation testing has been considered useful for diagnosing HP, but all patients gave negative results in short-term environmental exposure tests performed routinely for the diagnosis of HP. However, 5 patients had a positive response in long-term environmental exposure tests. Two patients died of respiratory failure after ten years' observation despite improvement of the causative environment, and were given steroid therapy. Radiographically and pathologically, the process of progressive and irreversible lesions were recognized in our series of CHP patients. The diagnosis of CHP should be carried out on the basis of the comprehensive findings including the detailed history, clinical course, radiography, and histology.

Alveolitis, Extrinsic Allergic↗

[An autopsy case of cor pulmonale due to a pulmonary tumor embolism as the first clinical manifestation of occult gastric cancer].

A 47-year-old man was admitted to our hospital because of progressive dyspnea and cough. Physical examination and chest radiographs showed the signs of cor pulmonale. A lung scan using perfused radionuclide revealed multiple peripheral perfusion defects and catheterization of the right heart showed severe pulmonary hypertension. A diagnosis of severe pulmonary embolism was made. Despite intensive care with anti-coagulation therapy, the patient died on the third-hospital day. Autopsy disclosed gastric cancer in the pylorus with metastases to the regional lymph nodes. There were no macroscopic pulmonary artery emboli or parenchymal lesions, but more than 60% of the small arteries and arterioles were occluded by casts of tumor cells. Cor pulmonale due to a pulmonary tumor embolism is a rare complication of cancer. This case is particularly unusual because the embolus-caused cor pulmonale was the initial manifestation of clinically occult, but pathologically advanced, gastric cancer.

Adenocarcinoma↗