Biomedical subjects

Hirohisa Yoshizawa

Publications and source records attributed to Hirohisa Yoshizawa.

13 recordsLinked to original sources

PubMed2006

Eradication of established tumors in mice by a combination antibody-based therapy.

Tumor-cell apoptosis is the basis of many cancer therapies, and tumor-specific T cells are the principal effectors of successful antitumor immunotherapies. Here we show that induction of tumor-cell apoptosis by an agonistic monoclonal antibody to DR5, the apoptosis-inducing receptor for TNF-related apoptosis-inducing ligand (TRAIL), combined with T-cell activation by agonistic monoclonal antibodies to the costimulatory molecules CD40 and CD137, potently and rapidly stimulated tumor-specific effector CD8+ T cells capable of eradicating preestablished tumors. Primary fibrosarcomas initiated with the carcinogen 3-methylcholanthrene (MCA), multiorgan metastases and a primary tumor containing as many as 90% tumor cells resistant to DR5-specific monoclonal antibody were rejected without apparent toxicity or induction of autoimmunity. This combination therapy of three monoclonal antibodies (trimAb) rapidly induced tumor-specific CD8+ T cells producing interferon (IFN)-gamma in the tumor-draining lymph node, consistent with a crucial requirement for CD8+ T cells and IFN-gamma in the tumor rejection process. These results in mice indicate that a rational monoclonal antibody-based therapy that both causes tumor-cell apoptosis through DR5 and activates T cells may be an effective strategy for cancer immunotherapy in humans.

Animals↗

PubMed2006

[A case of squamous cell carcinoma of unknown primary site with involvement of cervico-mediastinal lymph nodes successfully treated by chemoradiotherapy].

A 70-year-old woman was admitted with cervicomediastinal lymph node metastases from squamous cell carcinoma of unknown primary site (Sq-CUPS). The patient was treated with 4 cycles of chemotherapy combining carboplatin and paclitaxel with subsequent radiation therapy. After serial treatment, a partial response was obtained, and the disease has not recurred for over 2 years. Chemotherapy with carboplatin and paclitaxel followed by sequential radiation therapy was suggested to be potentially useful for Sq-CUPS with involvement of cervicomediastinal lymph nodes, although this group of patients is generally regarded to have a poor prognosis.

Aged↗

PubMed2005

Both regulatory T cells and antitumor effector T cells are primed in the same draining lymph nodes during tumor progression.

The peripheral tolerance mechanism prevents effective antitumor immunity, even though tumor cells possess recognizable tumor-associated Ags. Recently, it has been elucidated that regulatory T cells (Treg) play a critical role in maintaining not only self-tolerance, but also tolerance of tumor cells. However, because the Treg that maintain self-tolerance arise naturally in the thymus and are thought to be anergic in peripheral, it is still unclear where and when Treg for tumor cells are generated. In this study we analyze tumor-draining lymph nodes (LNs) and demonstrate that both antitumor effector T cells and Treg capable of abrogating the antitumor reactivity of the effector T cells are primed in the same LNs during tumor progression. The regulatory activity generated in tumor-draining LNs exclusively belonged to the CD4(+) T cell subpopulation that expresses both CD25 and a high level of CD62L. Forkhead/winged helix transcription factor gene expression was detected only in the CD62L(high)CD4(+)CD25(+) T cells. CD62L(high)CD4(+)CD25(+) Treg and CD62L(low)CD4(+)CD25(+) T cells, which possess effector T cell functions, had comparable expression of LFA-1, VLA-4, CTLA-4, lymphocyte activation gene-3, and glucocorticoid-induced TNFR. Thus, only CD62L expression could distinguish regulatory CD4(+)CD25(+) cells from effector CD4(+)CD25(+) cells in draining LNs as a surface marker. The Treg generated in tumor-draining LNs possess the same functional properties as the Treg that arise naturally in the thymus but recognize tumor-associated Ag. CD62L(high)CD4(+)CD25(+) Treg contained a subpopulation that expressed CD86. Blocking experiments revealed that ligation of CTLA-4 on effector T cells by CD86 on Treg plays a pivotal role in regulating CD4(+) effector T cells.

Animals↗

PubMed2005

Contribution of aspirin-intolerant asthma to near fatal asthma based on a questionnaire survey in Niigata Prefecture, Japan.

OBJECTIVE: Prevention of deaths due to asthma is one of the most important issues in asthma management. However, there are few epidemiological studies of asthma deaths in Japan. METHODOLOGY: Over an 8-week period in Niigata Prefecture, Japan, a questionnaire on asthma control and emergency episodes was administered to adult asthmatic patients. A questionnaire was also given to the patients' physicians to obtain further clinical information. Patients who became unconscious during episodes of asthma, or who required intubation and ventilation, were allocated to a near-fatal asthma group (NFA). Patients who did not fulfill these criteria were allocated to the non-NFA group. The NFA group was divided into two subgroups, based on the date of their last NFA episode (old NFA>or= 5 years and recent NFA<4 years). RESULTS: Characteristic features of the NFA group included severe disease (23.1%vs 7.6%) with more aggressive patient management, including inhaled corticosteroid use (84.3%vs 72.0%). Multiple regression analysis confirmed that aspirin-intolerant asthma (AIA) was strongly associated with NFA. There was no difference in the incidence of AIA between the recent and old NFA patients. This suggests the incidence of AIA in NFA did not improve over time. CONCLUSIONS: A history of AIA may be a useful indicator of potential NFA and allow preventative methods to be introduced. It is therefore important to obtain a history of AIA and to be aware of the risk of NSAID administration to these patients.

Adult↗

PubMed2005

Facial axis angle as a risk factor for obstructive sleep apnea.

OBJECTIVE: Many Japanese patients with obstructive sleep apnea (OSA) are less obese than Caucasian OSA patients despite their similar severity of OSA, suggesting that their etiology of OSA may differ. The purpose of this study was to identify bony factors associated with OSA in the Japanese population. METHODS: The clinical records of study subjects were retrospectively reviewed, and cephalometric measurements based on Sella-Nasion references and the Ricketts method were statistically compared. PATIENTS: Two hundred and six consecutive Japanese men complaining of habitual snoring and daytime sleepiness were enrolled in the study. All subsequently underwent an overnight polysomnographic examination. RESULTS: Multiple regression analysis showed that the body mass index (p<0.0001) and facial axis angle (p=0.007) were the dominant overall determinants for the apnea hypopnea index. The sella to nasion to subspinale angle (SNA) and sella to nasion to supramentale angle (SNB) were lower in the non-obese, severe group than for non-obese, mild and moderate patients with OSA (p=0.0047 and 0.0016, respectively). CONCLUSION: The risk factors for OSA in Japanese men may be obesity and the dolico facial pattern seen by the Ricketts method. In addition, a smaller SNA and SNB seem to be associated with the severity of OSA in non-obese patients.

Adult↗

PubMed2004

Short-term use of continuous positive airway pressure ameliorates glomerular hyperfiltration in patients with obstructive sleep apnoea syndrome.

Patients with OSAS (obstructive sleep apnoea syndrome) demonstrate renal signs such as proteinuria, glomerular hypertrophy and focal glomerular sclerosis. We performed a clinical study to investigate the glomerular function in OSAS patients and the short-term effect of CPAP (continuous positive airway pressure) on it. OSAS patients underwent a sodium thiosulphate and p-aminohippurate double clearance test, polysomnography and ambulatory blood pressure monitoring before and a week after the induction of CPAP. Twenty-seven consecutive patients (24 males) with moderate-to-severe OSAS admitted to our hospital for the induction of CPAP, and 32 healthy donors for renal transplantation as controls participated in the study. Before treatment, the glomerular filtration rate, estimated by the sodium thiosulphate clearance test, was within normal range, and the renal plasma flow was significantly lower than normal in the OSAS patients, thus the FF (filtration fraction) value was much higher than normal. FF before CPAP was not significantly correlated with age, body mass index or blood pressure; however, indices of increased hypoxaemia correlated with increased FF values. Polysomnographic variables after CPAP showed significant improvements in all patients, and only the nocturnal blood pressures were slightly lower than before CPAP. In 21 patients who underwent the clearance test after CPAP, FF significantly decreased from 0.26 +/- 0.04 to 0.23 +/- 0.03 (P < 0.001). OSAS patients were generally in a glomerular-hyperfiltrating condition that appeared to cause the renal findings associated with OSAS. CPAP might prevent nephropathy by ameliorating the glomerular hyperfiltration in OSAS patients.

Aged↗

PubMed2004

Tracheo-bronchitis associated with Crohn's disease improved on inhaled corticotherapy.

We report a case of tracheo-bronchitis in Crohn's disease. A 23-year-old Japanese woman who had been diagnosed with Crohn's disease three years previously was hospitalized. She had been suffering from dry cough for one month. Computed tomography of the chest revealed marked thickening of the tracheal wall. Bronchoscopy showed erythematous and edematous mucosa with diffuse whitish granular lesions in the trachea and bronchi. The bronchial biopsy specimens showed non-specific inflammatory infiltrates consisting of lymphocytes and plasma cells, and hyperplasia of bronchial glands. Inhaled corticotherapy, fluticasone propionate 800 microg/day, was effective for both the inflammatory mucosa and thickened tracheal wall.

Administration, Inhalation↗

PubMed2004

[A case of recurrent pulmonary lymphoepithelioma-like carcinoma responding to treatment with CBDCA/paclitaxel combined chemotherapy].

A 57-year-old female underwent left lower lung lobectomy and was histologically diagnosed as having lymphoepithelioma-like carcinoma. One year and 2 months after surgery, pleural thickening was recognized, so she was administered 4 courses of CBDCA/PTX combined chemotherapy. Toxicity associated with the chemotherapy was very mild. Pleural thickening and effusion disappeared after treatment, so this case was judged to be a complete response. She suffered from left chest pain before chemotherapy, which later lessened. She was thus able to stop taking NSAIDs. Because primary pulmonary lymphoepithelioma-like carcinoma is a rare tumor, there is no standard chemotherapy treatment. CBDCA/PTX combined chemotherapy is effective for pulmonary lymphoepithelioma-like carcinoma and shows good tolerability and improves QOL.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

[A case of primary pleural leiomyoma].

The chest radiograph = of a 33-year-old man showed a mass shadow in the right hilum. CT scanning film revealed a 3 x 2 cm tumor lying against the right pulmonary artery. Bronchoscopy and pulmonary arteriography showed almost normal findings. VATS tumor extirpation was performed. Macroscopically, the tumor was located in a major fissure. The resected specimen was compatible with leiomyoma. Because no organ of origin of the leiomyoma, other than the pleura, was detected, this case was diagnosed as a primary pleural leiomyoma. Primary pleural leiomyoma is very rare, and this report presents the first such case reported in Japan.

Adult↗

PubMed2003

The duration of signaling through CD40 directs biological ability of dendritic cells to induce antitumor immunity.

Although it has been demonstrated that the functions of dendritic cells (DCs), including Ag capture, Ag presentation, and migratory activity, change dynamically with their maturation, the most appropriate conditioning of DCs for anticancer immunotherapy is still unclear. The help signal is one of the most potent stimuli for DC maturation and is provided by the interaction of CD40 expressed on DCs with CD40 ligand on CD4(+) T cells. To elucidate the appropriate conditioning of DCs for anticancer immunotherapy, we examined the biological activity of DCs stimulated with immobilized anti-CD40 Ab. DCs stimulated for 3 h (3h-DCs) still showed an immature phenotype, but exhibited augmented migration toward secondary lymphoid tissues. Subcutaneous injection of 3h-DCs facilitated priming of T cells, which could mediate potent antitumor therapeutic efficacy, in draining lymph nodes and successfully induced protective immunity. In contrast, 24h-DCs showed a mature phenotype with good Ag presentation ability to induce cell killing by adoptively transferred CD8(+) T cells when injected at tumor sites; however, they showed no migratory activity and were unable to induce protective immunity when injected s.c. This is the first report that functionally distinct DCs, either for the priming phase or for the effector phase, could be obtained by conditioning with CD40 stimulation and that the duration of stimulation determines the biological outcome. The usage of DCs conditioned for the priming phase might provide significant advantages in anticancer immunotherapy.

Animals↗

PubMed2003

[Two cases of interstitial pneumonia with anti-Jo-1 antibodies in the absence of myositis].

We present two cases of interstitial pneumonia with anti-Jo-1 antibodies in the absence of myositis. The first patient was a 38-year-old woman and the second, a 59-year-old woman. Both patients were admitted to our hospital complaining of dry cough and dyspnea on effort. The diagnosis of interstitial pneumonia was made from chest radiography, computed tomography and surgical lung biopsy. Anti-Jo-1 antibodies, which were highly specific for polymyositis and dermatomyositis (PM/DM), were detected in both patients. However, the serum creatine kinase concentrations and electromyographic findings in both patients were normal, and no clinical signs (including muscle weakness, rash and arthralgia) were found. In the first patient, oral prednisolone (PSL) treatment (20 mg day) improved the interstitial pneumonia, but PSL has now been tapered to 17.5 mg day. In the second patient, oral PSL treatment (40 mg day) improved interstitial pneumonia, and the dose was tapered to 5 mg day. The second patient was followed for more than 10 years after treatment, but she has never shown any signs of clinical myositis. Further investigation will be required, because no pathophysiological relation between anti-Jo-1 antibodies and interstitial pneumonia with PM DM has yet been established.

Adult↗

PubMed2003

[Cyclosporin improved pure red cell aplasia associated with thymoma and tended to decrease thymoma size: a case report].

The case was a 56-year-old man who underwent extended thymothymectomy in 1993 because of an invasive thymoma classified as Masaoka IIa. The tumor was disseminated through the right thoracic cavity in 1994. Although the chemotherapy was repeated, the disseminated thymoma tended to increase in size. The patient was suffering from severe anemia, and pure red cell aplasia was diagnosed in September 2002. The administration of cyclosporin was initiated, and not only brought about improvement of pure red cell aplasia but also tended to shrink the thymoma. Cyclosporin may be an effective drug for the reduction of thymoma as well as for pure red cell aplasia.

Cyclosporins↗

PubMedDate not supplied

Matrix metalloproteinase-1 activation via plasmin generated on alveolar epithelial cell surfaces.

Plasmin is a potent protease related to tissue repair/remodeling not by fibrinolysis alone but also by activation of cytokines such as transforming growth factor and hepatocyte growth factor and by activation of matrix metalloproteases. We examined whether matrix matalloproteinase-1 was activated via plasminogen activation on surfaces of cultured alveolar epithelial cells (A-549). Cells were cultured overnight with plasminogen, pro-matrix metalloproteinase-1, and type I collagen as a substrate. Sodium dodecil sulfate-polyacrylamide gel electrophoresis was used to detect type I collagen degradation in culture supernatant. Collagen degradation corresponded to cell surface plasmin generation. No such finding was seen in the absence of cells or plasminogen. Alveolar epithelial plasminogen activation is important in matrix metalloproteinase-1 activation and thus presumably in tissue remodeling in pulmonary fibrosing pulmonary diseases such as idiopathic pulmonary fibrosis.

Cells, Cultured↗