Biomedical subjects

Shigeki Sato

Publications and source records attributed to Shigeki Sato.

At least 37 records · Page 2Linked to original sources

PubMed2004

Matrix metalloproteinase-1 polymorphism of promoter region in sarcoidosis and tuberculosis patients.

BACKGROUND AND AIM OF THE WORK: Matrix metalloproteinases (MMPs) are associated with several diseases. MMP-1 is one of the interstitial collagenases and the most highly expressed. Recent studies have found that a single nucleotide polymorphism located in the promoter region of the MMP-1 gene affects transcriptional activity. This polymorphism, 1G/2G, has been reported to associate with several malignant tumors and lung diseases. In this study, we investigated whether this polymorphism is associated with sarcoidosis or tuberculosis. METHODS: Polymerase chain reaction-restriction fragment length polymorphism was used to determine the MMP-1 genotypes of 103 sarcoidosis patients, 105 tuberculosis patients and 106 healthy control subjects. RESULTS: We found no differences in genotype distributions and allele frequency between sarcoidosis or tuberculosis patients and healthy control subjects. In sarcoidosis patients with ocular involvement, a significant increase in 1G/1G or 1G/2G genotype was observed compared with patients without (p = 0.009, odds ratio (OR) = 3.22, 95% confidence interval (CI): 1.34-7.71). In sarcoidosis patients with three or more organs involved, 1G/1G type tended to increase compared with patients without (p = 0.035, OR = 5.17, 95% CI: 1.12-23.9). In tuberculosis patients with cavity formation, an increasing trend of 1G/1G type was observed compared with patients without (p = 0.064, OR = 7.69, 95% CI: 0.89-66.3). CONCLUSIONS: Although MMP-1 polymorphism was not associated with onset risk of sarcoidosis and tuberculosis, the clinical characteristics of both diseases were affected by this polymorphism.

Adult↗

PubMed2004

Determinants of sensitivity and resistance to gemcitabine: the roles of human equilibrative nucleoside transporter 1 and deoxycytidine kinase in non-small cell lung cancer.

Gemcitabine is one of the most commonly used agents for lung cancer chemotherapy, but the determinants of sensitivity and/or resistance to this agent are not yet fully understood. In this study we used quantitative RT-PCR to examine the expression levels of human equilibrative nucleoside transporter 1 (hENT1) and deoxycytidine kinase (dCK) genes in non-small cell lung cancer (NSCLC) cell lines in relation to sensitivity and resistance to gemcitabine. The basal expression levels of hENT1 were significantly correlated with the IC50 values for gemcitabine (r =-0.6769, P = 0.0005), whereas dCK expression levels were not. In a highly gemcitabine-sensitive cell line, NCI-H23, the sensitivity to gemcitabine was inhibited by nitrobenzylmercaptopurine ribonucleoside (NBMPR), an inhibitor of hENT1, without significant modulation of hENT1 expression. These data suggest that hENT1 is associated with gemcitabine sensitivity in lung cancer. We also continuously exposed NCI-H23 cells to gemcitabine and subsequently established the drug-resistant clone H23/GEM-R, which showed a significant decrease of dCK expression; however, hENT1 expression was not altered in the continuously exposed sublines or in the resistant clone. We conclude that increased hENT1 expression is a determinant of gemcitabine sensitivity, while decreased dCK expression is associated with acquired resistance to gemcitabine in NSCLC cells. Thus, hENT1 and dCK might be useful as predictive markers for efficacy of gemcitabine therapy in NSCLC.

Affinity Labels↗

PubMed2004

Microscopic polyangiitis associated with diffuse panbronchiolitis.

There are several case reports of systemic vasculitis associated with chronic suppurative lung diseases. We describe a 46-year-old female, previously diagnosed as having diffuse panbronchiolitis (DPB), presenting with hemosputum and dyspnea. Her serum titer of MPO-ANCA was positive together with a high titer of BPI-ANCA. Chest X-ray and chest CT scan showed pulmonary hemorrhage, and the renal biopsy specimen revealed necrotizing, crescentic glomerulonephritis. She was diagnosed as having ANCA-associated vasculitis, and more specifically, microscopic polyangiitis accompanied by DPB. She was treated with methylprednisolone pulse therapy, followed by intravenous cyclophosphamide. This case suggested a possible association with chronic bacterial infection, which may play a role in the pathogenesis of ANCA-associated vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed2004

[A case of gastric cancer with a synchronous hepatic metastasis responding to postoperative oral administration of UFT and intermittent intrahepatic arterial chemotherapy of 5-FU].

A 65-year-old male was admitted to our hospital because of sudden onset of upper abdominal pain due to the perforation of gastric cancer with synchronous hepatic metastasis. He underwent total gastrectomy with lymphatic dissection of D1 + alpha. Pathological diagnosis of the surgical specimen was moderately differentiated tubular adenocarcinoma. The cancer progression was fStage IV (T1, N0, H1, P0). Since 50 days after surgery, he had received oral administration of UFT (300-600 mg/day) and intermittent intrahepatic arterial infusion of 5-FU (one injection, 500 mg/2 weeks). Seven months after the start of chemotherapy, the size of hepatic lesion was reduced. Thirteen months later, the tumor became necrotic with cystic change. Furthermore, 22 months later, abdominal CT scan showed complete response. He has been well without recurrence for 38 months following the start of chemotherapy.

Adenocarcinoma↗

PubMed2003

Analysis of beta-tubulin gene alteration in human lung cancer cell lines.

We examined lung cancer cell lines for the presence of beta-tubulin gene alteration based on a previous report of a relationship between frequent beta-tubulin gene mutation in non-small-cell lung cancer and clinical response to taxanes as well as the prognosis. The mutation was defined by analyzing genomic DNA from 31 lung cancer cell lines by direct genomic sequencing using specific primers for the beta-tubulin class I gene. We detected only three genetic alterations at nonsplice sites in two introns, and a silent genetic alteration at codon 217 in exon 4. The mutation of the beta-tubulin gene was rare; moreover, these genetic alterations were predicted to evoke no biological alteration of the cancer cells. Our data suggest that the beta-tubulin gene mutation does not play a major role in the genetic mechanism of resistance to taxanes. In addition, the presence of a closely related family of beta-tubulins or pseudogenes was thought to hinder accurate evaluation of the beta-tubulin gene.

Codon↗

PubMed2003

Physical therapy for benign paroxysmal positional vertigo patients with movement disability.

OBJECTIVE: Particle repositioning manoeuvres are broadly recognized effective for benign paroxysmal positional vertigo (BPPV), however, we think that these therapies are not suitable for all BPPV patients. In this study we investigate whether these manoeuvres can be used for BPPV patients with the movement disability. In addition, we introduce our habituation training (HT) and report the results of treatment with it. METHODS: Nine BPPV patients with the movement disability due to orthopedic disease were examined. For each patient we determined their movement disabilities, and assessed the suitability of particle repositioning manoeuvres, Brandt-Daroff (B-D) manoeuvre and HT for them. RESULTS: All of these nine patients had neck or trunk movement disabilities due to orthopedic disease, and we judged that particle repositioning manoeuvres and B-D manoeuvre were impossible or too risky to be employed in them. Although HT was suitable for them and symptoms and signs of them improved within a short period of time. CONCLUSION: Particle repositioning manoeuvres were not suitable for BPPV patients with the movement disability because these manoeuvres required various movements. These patients were able to perform HT depending on their capabilities. We think that HT is caused by the fatigability of BPPV, and it accelerates the natural curing process.

Aged↗

PubMed2003

Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells.

We have shown previously that KIAA0223, a gene encoding a minor histocompatibility antigen, HA-1, whose expression was believed to be restricted to the hematopoietic cells, is aberrantly expressed in some solid tumor cell lines. However, its significance in tumor immunity needs to be determined. Cytotoxic activity of HA-1(H)-specific cytotoxic T lymphocytes (CTLs) was assessed against solid tumor cell lines expressing KIAA0223 using (51)Cr release assays. Five of seven cell lines were lysed when HLA-A*0201 was adequately expressed. One of the two CTL-resistant cell lines became susceptible after treatment with IFN-gamma and TNF-alpha, while the other was lysed only after pulsing with HA-1(H) peptide. In most cell lines tested, HA-1(H) peptide was properly generated and presented for recognition by the CTL. However, impaired antigen processing and presentation observed in this study may result in escape from CTL recognition in vivo, as well as in vitro, as observed in this study.

Gene Expression Regulation, Neoplastic↗

PubMed2003

Myofibroblasts proliferation of idiopathic and collagen vascular disorders associated nonspecific interstitial pneumonia.

Nonspecific interstitial pneumonia (NSIP) has been recognized as a separate histological classification of interstitial lung disease. Similar features are found not only in idiopathic NSIP, but also in NSIP associated with collagen vascular disorder (CVD-NSIP). We examined the clinical symptoms, laboratory findings, and prognosis of 13 cases of idiopathic NSIP and 11 cases of CVD-NSIP. Immunohistochemical staining was performed using the streptavidin/biotin/peroxidase method with anti-alpha-smooth muscle actin antibody. No differences in the distribution of clinical features, laboratory findings, and prognosis were observed between idiopathic NSIP and CVD-NSIP. In immunohistochemical staining of the fibrosing areas, myofibroblasts were observed in 7 of 13 idiopathic NSIP cases, but in 10 of 11 CVD-NSIP cases. With regards to intra-alveolar organization, myofibroblasts were observed in all 10 CVD-NSIP cases, but they were observed in only 2 of 9 idiopathic NSIP cases. We found a significantly higher myofibroblast proliferation in the intra-alveolar organization of CVD-NSIP compared to idiopathic NSIP. Clinically, idiopathic NSIP and CVD-NSIP are similar, but are pathologically different.

Aged↗

PubMed2003

[A case of sarcoidosis with rheumatic features (Löfgren's syndrome)].

Rheumatoid arthritis was diagnosed in a 30-year-old woman with erythema nodosum and arthritic symptoms since 1994, and she was treated with anti-rheumatic agents. Mediastinal and bilateral hilar lymphadenopathy and abnormal pulmonary shadows were detected in 1996, and she was admitted to our hospital in 1997. We also recognized the elevation of ACE and lysozyme, and found granulomas in a transbronchial lung biopsy and an arthrosis synovia biopsy. From these findings, sarcoidosis was diagnosed. Sarcoidosis demonstrating erythema nodosum, arthritis, and bilateral hilar lymphadenopathy is called Löfgren's syndrome. In Caucasians, Löfgren's syndrome is frequently encountered, but it is rare in Japanese. Our case had coexisting arthrosis symptoms, and satisfied the diagnosis criteria of rheumatic arthritis. Therefore, the differential diagnosis was important. We emphasize that it is necessary to consider Löfgren's syndrome when diagnosing patients with rheumatic features, even in Japan.

Adult↗

PubMed2003

Cortical potentials evoked by horizontal rotatory stimulation: the effects of angular acceleration.

OBJECTIVE: To examine the potentials evoked by rotatory stimulation, which we consider the optimal means of invoking angular acceleration and which may lead to clinical applications in patients with vertigo. MATERIAL AND METHODS: Horizontal rotatory stimulation using a trapezoidal waveform was performed with 3 different angular accelerations (20, 15 and 10 degrees/s2) used sequentially, with alternating clockwise and counterclockwise stimulation, to normal subjects and a patient with bilateral loss of vestibular function. RESULTS: It is likely that angular accelerations of < 20 degrees/s2 produce minor somatosensory effects. Clear potentials were evoked in 13/18 ears (72%) of the normal subjects with stimulation at an angular acceleration of 15 degrees/s2. No response was recorded in the patient with stimulation at 15 degrees/s2. CONCLUSION: We suggest that an angular acceleration of 15 degrees/s2 is optimal for clinical examinations.

Acceleration↗

PubMed2002

An anti-GD2 monoclonal antibody enhances apoptotic effects of anti-cancer drugs against small cell lung cancer cells via JNK (c-Jun terminal kinase) activation.

Small cell lung cancer (SCLC) cell lines specifically express ganglioside GD2, and anti-GD2 monoclonal antibodies (mAbs) caused suppression of cell growth and induced apoptosis of SCLC cells with single use. Here, enhancement of the cytotoxic effects of various anti-cancer drugs with an anti-GD2 mAb was demonstrated. The cytotoxicity of all six drugs examined was markedly enhanced, i.e. 2.4 - 7.8-fold increase of cell sensitivity in terms of IC(50). In particular, the combination of cisplatin (CDDP) with an anti-GD2 mAb resulted in prominent enhancement of cytotoxicity even in low - moderate GD2-expressing lines. The anti-GD2 mAb induced weak activation of c-Jun terminal kinase (JNK) in SCLC cells, and all anti-cancer drugs also induced its activation to various degrees. When CDDP and an anti-GD2 mAb were used together, significantly stronger JNK activation was observed corresponding to the cytotoxic effects, suggesting that synergistic phosphorylation of JNK with two reagents induced prominent apoptosis. The essential role of JNK in the induction of SCLC apoptosis with CDDP and anti-GD2 mAb was confirmed by experiments with a JNK inhibitor, curcumin. These results suggest that anti-GD2 mAbs would be very efficient in combination with anti-cancer drugs, both to achieve SCLC-specific cytotoxicity and to enhance its magnitude.

Antibodies, Monoclonal↗

PubMed2002

p185(HER-2/neu) and p21(CIP1/WAF1) expression in primary tumors and lymph node metastases in non-small cell lung cancer.

p185(HER-2/neu), a tyrosine kinase receptor, is one of the target molecules for cancer therapy, and its expression may reduce the sensitivity of tumor cells to anti-cancer drugs. p21(CIP1/WAF1) is a cyclin-dependent kinase inhibitor, and its expression may also be involved in chemoresistance. Non-small cell lung cancer (NSCLC) is a potentially systemic disease, and systemic therapies play an important role in its treatment. However, there have been no studies comparing the expression of these molecules between primary and metastatic tumors. We investigated the expression of p185(HER-2/neu) and p21(CIP1/WAF1) in 57 paired samples of primary NSCLC tumors and corresponding lymph node metastases by immunohistochemistry. Expression of each of p185(HER-2/neu) and p21(CIP1/WAF1) was highly correlated between primary tumors and lymph node metastases, and similar correlations were also obtained when adenocarcinoma and squamous cell carcinoma cases were analyzed individually. However we failed to detect any correlation between p185(HER-2/neu) and p21(CIP1/WAF1) expression. Our results suggested that expression of both p185(HER-2/neu) and p21(CIP1/WAF1) is concordant between primary and metastatic tumors.

Adult↗

PubMed2002

A study on intraalveolar exudates in acute mycoplasma pneumoniae infection.

Pathologic features of Mycoplasma pneumoniae infection (M. pneumonia) are generally non-specific, and the literature regarding the pathologic features of M. pneumonia with intraalveolar exudates is limited. Clinical and histopathological studies were performed in 3 patients with M. pneumonia which did not respond to erythromycin and minocycline, but all rapidly recovered after corticosteroid therapy. In pathologic findings, we observed intraalveolar exudates and focal organization in M. pneumonia, and its intraalveolar lesions were compared between M. pneumonia and bronchiolitis obliterans organizing pneumonia containing fibrin (BOOP). Immunohistochemical studies were performed using the streptavidin biotin peroxidase complex method with anti-alpha-smooth muscle actin antibody and anti-pancytokeratin AE1/AE3 antibody. In pathologic findings, more fibrin deposits in intaalveolar lesions were observed in M. pneumonia than in BOOP. In intaalveolar lesions of M. pneumonia, a larger amount of nuclear debris, more neutrophils, and more erythrocytes were noted. Myofibroblasts were observed in the organization of BOOP, while in the intaalveolar lesions of M. pneumonia, myofibroblasts were not observed. These results suggest that M. pneumonia with intraalveolar exudates responds well to corticosteroid and its intraalveolar lesions apparently differed from those in BOOP.

Acute Disease↗

PubMed2002

A limited association of OGG1 Ser326Cys polymorphism for adenocarcinoma of the lung.

The 8-oxoguanine DNA glycosylase (OGG1) repairs DNA by removing 8-hydroxyguanine, a highly mutagenic oxidative DNA adduct. Recently, the gene for OGG1 was cloned and several polymorphisms have been reported. Because environmental carcinogens produce 8-hydroxyguanine residues that potentially cause oncogenic mutations by mismatching to this modified base, the capacity to repair these lesions can be involved in cancer susceptibility. This study investigated the association between OGG1 Ser326Cys polymorphism and risk of the lung adenocarcinoma for Japanese by a prevalent case-control study in Japan. The subjects comprised 138 cases and 241 non-cancer outpatients as controls. OGG1 gene polymorphism was genotyped by a PCR-CTPP (polymerase chain reaction with confronting two-pair primers) method. The distribution of OGG1 Ser326Cys genotype among controls (Ser/Ser, 28.3%; Ser/Cys, 49.2%; and Cys/Cys, 22.5%) was not different from that among cases (Ser/Ser, 29.0%; Ser/Cys, 51.4%; and Cys/Cys, 24.0%). The sex-age adjusted odds ratio (OR) was 1.06 with 95% confidence interval (CI) 0.64-1.76 for Ser/Cys genotype and 0.81 with 0.44-1.52 for Cys/Cys genotype. The ORs according to the interval between diagnosis and study enrollment were also examined because the polymorphism was a potential prognostic factor of lung cancer. The ORs of Ser/Cys and Cys/Cys genotypes in the cases less than 3 years after diagnosis were higher than overall ORs; 1.86 (95%CI, 0.91-3.77), and 1.46 (0.64-3.35), respectively. The OR for smoking was not statistically different among genotype, though the sample size was too small to detect even a moderate interaction. This study supported the first study by Sugimura et al (Cancer Epidemiol Biomarkers Prev, 1999; 8: 669-674), that the association of OGG1 Ser326Cys polymorphism was limited for the risk of lung adenocarcinoma.

Adenocarcinoma↗

PubMed2002

[Adenocarcinoma of the lung with skeletal muscle metastasis, resulting in death due to myocardial metastasis: a case report].

A 57-year-old man was admitted to the hospital because of multiple subcutaneous masses with pain, mild dyspnea, and bloody sputum. He had been asymptomatic until one month earlier, when he began to have a dry cough and myalgia of the right forearm. A chest radiograph showed cardiomegaly. Whole-body computed tomographic scan, cytologic examination of the sputum, and histological examination of a subcutaneous nodule on the scalp resulted in the diagnosis of lung cancer with multiple organ metastases, including those to skeletal muscle and myocardium. Despite chemotherapy, he died suddenly on the 45th hospital day. Autopsy revealed that about half of the myocardium had been replaced by metastatic tumors, so we speculated that he died from heart failure due to cardiac muscle metastasis.

Adenocarcinoma↗

PubMed2002

[Recurrence of thymoma accompanied with hypogammaglobulinemia 20 years after surgery: a case report].

We reported a case of recurrence of localized thymoma accompanied with hypogammaglobulinemia (Good's syndrome) 20 years after surgery. A 74-year-old man was admitted to this hospital because of mediastinal tumor and chronic pulmonary infection. He had been thymectomised at the age of 55 because of spindle cell thymoma. After that, he had been asymptomatic until January 1997, when he began to have a recurrent productive cough, and low-grade fever. Laboratory findings revealed hypogammaglobulinemia. Percutaneous needle biopsy of the mediastinal tumor revealed spindle cell thymoma. Therefore, hypogammaglobulinemia with thymoma (Good's syndrome) accompanied with a chronic lower respiratory tract infection was diagnosed. Immunologic studies revealed a marked decrease of CD 20 positive cells and decreased lymphocyte activation under the stimuli of phytohemagglutinin and concanavalin A. The thymoma was resected in Dec 1997, but the serum immunoglobulin showed no increase at al.

Agammaglobulinemia↗

PubMed2002

[Monoclonal antibody for cancer treatment].

Antibodies have for many decades been viewed as ideal molecules for cancer therapy. Although promising from the start, it has taken much of more than two decades to reach the level of clinical application. Genetic engineering of antibodies; that is novel technologies for chimeric or humanizing monoclonal antibodies, has greatly advanced their utility in molecular targeting therapies, and in the past four years some therapeutic monoclonal antibodies for hematologic malignancies and solid tumors, such as Rituximab for B-cell lymphoma and Trastuzumab for metastatic breast cancer, have provided sufficient efficacy and safety to support regulatory approval from the U.S. Food and Drug Administration. They were subsequently approved by the Japanese Ministry of Health, Labour and Welfare in 2001. Many molecular biological and immunological studies have revealed the targeting properties of the host immune system and the biological mechanism of cancer cells for a more specific anticancer effect. Many clinical trials of monoclonal antibodies as a single agent, or in combination protocol with current standard chemotherapy or immunoconjugates have shown promise in the treatment of specific diseases. Furthermore, novel antibody designs and improved understanding of the mode of action of current antibodies lend great hope to the future of this therapeutic approach. The accumulating results from many basic, clinical and translational studies may lead to more individualized therapeutic strategies using these agent directed at specific genetic and immunologic targets.

Antibodies, Monoclonal↗

PubMed2002

[Bronchoalveolar lavage in sarcoidosis].

A characteristic feature of BAL in patients with sarcoidosis is an increase of the total cell number, lymphocytes percent, or CD4/CD8 ratio of T lymphocytes. With respect to T lymphocytes, sarcoidosis has been recognized as a granulomatous disease characterized by dominant expression of Th1 cytokines. Recently Th1 cytokine profile in both CD4+ and CD8+ T lymphocytes in BAL fluid were demonstrated at the single-cell level. Furthermore, alveolar macrophages collected from BAL fluid were also investigated. Increased expression of 25-hydroxyvitamin D3 1 alpha-hydroxylase with mRNA level in alveolar macrophage were revealed in active sarcoidosis. Previously we showed that the B allele of the vitamin D receptor gene polymorphism may be regarded as a risk factor in the onset of sarcoidosis. The metabolism of vitamin D may be related to granuloma formation.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗