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Biomedical subjects

S Ogura

Publications and source records attributed to S Ogura.

At least 19 recordsLinked to original sources
PubMed2006

A phase II trial of gefitinib as first-line therapy for advanced non-small cell lung cancer with epidermal growth factor receptor mutations.

Retrospective analysis has shown that activating mutations in exons 18-21 of the epidermal growth factor receptor (EGFR) gene are a predictor of response to gefitinib. We conducted a phase II trial to evaluate the efficacy and safety of gefitinib as first-line therapy for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. Patients with stage IIIB or IV chemotherapy-naïve NSCLC with EGFR mutation were treated with 250 mg gefitinib daily. For mutational analysis, DNA was extracted from paraffin-embedded tissues and EGFR mutations were analysed by direct sequence of PCR products. Twenty (24%) of the 82 patients analysed had EGFR mutations (deletions in or near E746-A750, n=16; L858R, n=4). Sixteen patients were enrolled and treated with gefitinib. Twelve patients had objective response and response rate was 75% (95% CI, 48-93%). After a median follow-up of 12.7 months (range, 3.1-16.8 months), 10 patients demonstrated disease progression, with median progression-free survival of 8.9 months (95% CI, 6.7-11.1 months). The median overall survival time has not yet been reached. Most of the toxicities were mild. This study showed that gefitinib is very active and well tolerated as first-line therapy for advanced NSCLC with EGFR mutations.

Administration, Oral↗
PubMed2004

Characterization of junctional sarcoplasmic reticulum Ca2+ content and release by short-term mechanical restitution in cardiac muscle.

To study Ca2+ handling by the junctional sarcoplasmic reticulum (JSR), the time course of short-term mechanical restitution after varying magnitudes of twitch contractions was assessed in rat papillary muscle. Mechanical restitution consisted of a pretwitch latency period followed by a rapid and a subsequent much slower restitution of twitch force. The rate of rapid restitution was independent of the magnitude of the preceding twitch, which suggests that the rate of JSR Ca2+ repletion was dependent on the amount of Ca2+ remaining in the JSR after a twitch contraction. Based on this finding, the functions Gt and Ht, representing the time courses of JSR Ca2+ repletion and release, respectively, were derived graphically from a family of the mechanical restitution curves. Gt increased monotonically with time at a decreasing rate, while Ht increased with time in a sigmoid manner. The mechanical alternans were simulated by using experimental values and mathematically predicted values of Gt and Ht. A substitution of extracellular Na+ with Li+ to inhibit Na+/Ca2+ exchange resulted in an augmentation of Gt by approximately 10%, presumably by increasing the tubular SR Ca2+ uptake. The inhibition of tubular SR Ca2+ uptake by thapsigargin (10 microM) reduced mechanical restitution by approximately 13% of the maximal twitch force, independent of the phase of mechanical restitution; the effect was greater at an earlier time point in the mechanical restitution. These results suggest that early JSR Ca2+ replenishment results mainly from the movement of Ca2+ from the tubular SR.

Adaptation, Physiological↗
PubMed2003

Primary amyloidosis with multiple pulmonary nodular lesions and IgA nephropathy-like renal involvement.

A 66-year-old woman demonstrated multiple nodular lesions in the lungs without symptoms, and laboratory tests and transbronchial lung biopsy (TBLB) had been negative for malignancy, tuberculosis and sarcoidosis 15 years ago. She developed proteinuria and hematuria 10 years later. Renal biopsy revealed focal segmental mesangial proliferation with predominant IgA deposition in the paramesangium, suggesting IgA nephropathy. However, electron-microscopic observation revealed 8-12 nm fibril deposits in the interstitium and few in the mesangium that were positively stained with amyloid P protein and negative for amyloid A protein. Re-evaluation of previous TBLB samples showed apple-green birefringence with Congo-red staining that was resistant to potassium permanganate reaction. Electron-microscopic observation with high magnification and immunostaining for amyloid components led to a diagnosis of AL amyloidosis in this patient with predominant mesangial IgA deposition and slowly progressive nodular lesions in the lungs.

Aged↗
PubMed2002

[Clinical study of eight thymic carcinomas].

Eight patients with thymic carcinoma were surgically treated at Sapporo City General Hospital from September 1990 to January 2002. The histological subtypes of thymic carcinoma were squamous cell in 5, undifferentiated in 2, and small cell in one. After median sternotomy, 5 patients had total resection of the tumor, and 3 had incomplete resection due to extensive mediastinal invasion involving the main pulmonary artery in the A-P window. Of 3 cases with intra pericardial malignant effusion, one patient survived 7 years without recurrence of the tumor after the exploratory operation followed by mediastinal irradiation without chemotherapy. In this patient, existence of the malignant cells in the pericardial effusion was not associated with poor outcome.

Adult↗
PubMed2001

Detection of lung tumor movement in real-time tumor-tracking radiotherapy.

PURPOSE: External radiotherapy for lung tumors requires reducing the uncertainty due to setup error and organ motion. We investigated the three-dimensional movement of lung tumors through an inserted internal marker using a real-time tumor-tracking system and evaluated the efficacy of this system at reducing the internal margin. METHODS AND MATERIALS: Four patients with lung cancer were analyzed. A 2.0-mm gold marker was inserted into the tumor. The real-time tumor-tracking system calculates and stores three-dimensional coordinates of the marker 30 times/s. The system can trigger the linear accelerator to irradiate the tumor only when the marker is located within the predetermined "permitted dislocation." The value was set at +/-1 to +/-3 mm according to the patient's characteristics. We analyzed 10,413-14,893 data sets for each of the 4 patients. The range of marker movement during normal breathing (beam-off period) was compared with that during gated irradiation (beam-on period) by Student's t test. RESULTS: The range of marker movement during the beam-off period was 5.5-10.0 mm in the lateral direction (x), 6.8-15.9 mm in the craniocaudal direction (y) and 8.1-14.6 mm in the ventrodorsal direction (z). The range during the beam-on period was reduced to within 5.3 mm in all directions in all 4 patients. A significant difference was found between the mean of the range during the beam-off period and the mean of the range during the beam-on period in the x (p = 0.007), y (p = 0.025), and z (p = 0.002) coordinates, respectively. CONCLUSION: The real-time tumor-tracking radiotherapy system was useful to analyze the movement of an internal marker. Treatment with megavoltage X-rays was properly given when the tumor marker moved into the "permitted dislocation" zone from the planned position.

Aged↗
PubMed2001

A risk-stratification model of non-small cell lung cancers using cyclin E, Ki-67, and ras p21: different roles of G1 cyclins in cell proliferation and prognosis.

A large number of biological factors that seem to have important prognostic significance have been identified in non-small cell lung cancers (NSCLCs). In the present study, we have characterized expression of cyclin D1 and cyclin E in a cohort of 217 resected NSCLCs from a single institution by immunohistochemistry to analyze their expression in relation to the growth fraction determined by Ki-67 and to prognosis, and then we have constructed a risk-stratification model of cancer death by multiple biological factors in p-stage I NSCLCs. The cyclin E labeling index (LI) was significantly associated with the Ki-67 LI (r = 0.45; P < 0.001). Tumors having high-level cyclin E expression (cyclin E LI > or =30%) showed a significantly higher Ki-67 LI than tumors having low-level cyclin E expression (cyclin E LI <30%; P < 0.001), whereas positive or negative cyclin D1 expression was not associated with the Ki-67 LI (P = 0.1). Cyclin E expression was a significant and independent unfavorable prognostic factor (hazards ratio = 2.09; P = 0.03), as reported previously (Clin. Cancer Res., 6: 11-16, 2000), whereas cyclin D1 expression was not. These findings indicate different roles of cyclin D1 and cyclin E in cell proliferation and in the prognosis of NSCLCs. Furthermore, we stratified this cohort of p-stage I NSCLCs into different survival groups by using biological factors, including cyclin E, Ki-67, and ras p21, which previously we have found to be independent prognostic factors among 10 factors studied in p-stage I NSCLCs. Four groups of patients with markedly different survivals were identified with 5-year survival rates that ranged from 96% for patients with no factors altered to 41% for patients with all three factors altered (P < 0.001). This combination of biological factors was a significant and independent prognostic factor (hazards ratio = 7.94; P = 0.001).

Aged↗
PubMed2001

A rare case of bronchial glomus tumor.

A 48-year-old man was admitted because of bloody sputum in whom a chest computed tomography (CT) scan and fiberoptic bronchoscopy demonstrated a polypoid tumor in the left main bronchus. The tumor was surgically resected, and the pathological and immunohistochemical findings led to diagnosis of the tumor as a bronchial glomus tumor.

Biopsy, Needle↗
PubMed2001

A loop-forming duplicate recurrent laryngeal nerve: report of a case and clinical relevance in thyroid surgery.

This is a report of a unilateral loop-forming duplicate recurrent laryngeal nerve and its clinical relevance. A 72-year-old woman with a giant goiter underwent a total thyroidectomy. At operation we identified two recurrent laryngeal nerves on the right side and one on the left side. The nerve on the right was smaller and displaced laterally by the goiter, whereas the other was adjacent to the trachea and behind the goiter, and it was accidentally divided. Both nerves were united before innervating the larynx. The divided nerve was microsurgically reanastomosed but a postoperative assessment revealed hoarseness. This case report of an anomalous loop-forming duplicate recurrent laryngeal nerve indicates that it may not be sufficient to identify a single recurrent laryngeal nerve on one side during thyroid surgery especially when the observed recurrent nerve is relatively smaller than usual.

Aged↗
PubMed2000

Intracellular distribution of macrophage migration inhibitory factor predicts the prognosis of patients with adenocarcinoma of the lung.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is known to be a proinflammatory cytokine and glucocorticoid-induced immunomodulator as well as a regulator of tumor growth. Although positive and negative effects of MIF on tumor cell growth have been reported, to the authors' knowledge the precise role of MIF in tumorigenesis remains unclear. In the current study the authors assessed expression of MIF protein and mRNA in lung adenocarcinomas with regard to patient prognosis. METHODS: Immunohistochemical analysis was performed on tissue specimens surgically obtained from 74 patients with primary lung adenocarcinoma (American Joint Committee on Cancer pathologic Stages I, II, and IIIa). In addition, expression of MIF mRNA in the cancerous tissue was investigated using in situ hybridization. Patient prognosis was evaluated with regard to MIF expression levels and its distribution was analyzed with the Kaplan-Meier method. RESULTS: MIF mRNA and MIF protein were observed in the bronchial epithelium, alveolar epithelium, vascular smooth muscle, and alveolar macrophages in the normal lung tissue. In tumor tissue from lung adenocarcinoma specimens, both MIF mRNA and protein were observed at much higher levels than in the normal alveolar epithelium. MIF protein was observed diffusely in the cytoplasm of tumor cells in all tumor specimens examined. MIF protein also was observed in the nuclei of tumor cells from 59 patients (79.7%), whereas it was not observed in the nuclei of tumor cells from 15 patients (20.3%). The patients without nuclear MIF expression had a worse prognosis compared with those patients with MIF expression in the nuclei (P = 0.04). CONCLUSIONS: The results of the current study suggest that intracellular MIF distribution predicts patient prognosis in individuals with adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed2000

Preparation of a water-soluble fluorinated zinc phthalocyanine and its effect for photodynamic therapy.

An amphiphilic fluorinated phthalocyanine, zinc tetracarboxyoctafluorophthalocyanine (ZnC4F8Pc) was synthesized and characterized. Its photodynamic efficiency for HeLa cells was compared with hydrophilic zinc octacarboxyphthalocyanine (ZnC8Pc) and hydrophobic zinc hexadecafluorophthalocyanine (ZnF16Pc). ZnC4F8Pc had a remarkable photodynamic effect among the phthalocyanines used. The effect is apparently caused by the fact that ZnC4F8Pc is mainly accumulated in the hydrophobic lipid membrane and is in the photoactive monomer form in HeLa cells.

Fluorine↗
PubMed2000

Effects of induced hypothermia on renal sympathetic nerve activity and baroreceptor reflex in urethane-anesthetized rabbits.

OBJECTIVE: To evaluate the role of the autonomic nervous system in hemodynamic changes during induced hypothermia. DESIGN: Prospective, randomized animal study. SETTING: An animal research laboratory in a medical university. SUBJECTS: A total of 29 anesthetized rabbits. INTERVENTIONS: Animals were anesthetized by intraperitoneal urethane. After tracheostomy and administration of gallamine, respiration was maintained by mechanical ventilatory support. The animals were divided into five groups (one control and the four experimental groups); animals were treated with an intact neuraxis and normothermia (control group), animals with an intact neuraxis (intact group), cervical vagotomized animals (vagotomy group), the carotid sinus and aortic nerves denervated animals (SAD group), and animals with SAD plus vagotomy (SADV group). The left renal sympathetic nerves were exposed by a retroperitoneal approach. MEASUREMENTS AND MAIN RESULTS: We examined the effects of surface cooling on HR, mean arterial pressure, central venous pressure, and renal sympathetic nerve activity (RSNA) in the animals. Changes of baroreflex sensitivity and plasma catecholamines were also measured simultaneously. Surface cooling caused progressive and profound decreases in HR in all experimental groups. In all groups, RSNAs increased at the early phase, which were followed by return to the precooling level. CONCLUSIONS: Hemodynamics and RSNA during induced hypothermia are regulated by mechanisms other than the baroreceptor reflex system, possibly the dermal cold receptors. Suppression of the baroreflex occurred on HR but not on RSNA during hypothermia, which may indicate direct effects of hypothermia on the heart. RSNA responses may be activated earlier than systemic catecholamine responses during induced hypothermia.

Adrenergic Fibers↗
PubMed2000

Effects of an antithrombin drug in patients with subacute exacerbations of Binswanger disease.

The blood coagulation system has been shown to be activated in subacute exacerbations of Binswanger disease (BD). In our previous study, the antithrombin drug argatroban t ameliorated the neurological exacerbations in a BD patient with antiphospholipid antibody syndrome. We have further examined the therapeutic efficacy of argatroban in 3 BD patients with subacute exacerbations, but without any immune-mediated prothrombotic complications. In 1 out of these 4 patients, treatment with sodium ozagrel, an antiplatelet drug was applied, but was ineffective. In all patients, argatroban treatment reduced the levels of the hemostatic markers, with a corresponding improvement in cognitive dysfunction and gait disorders. These results suggest that the antithrombin effect is true also for BD patients not compromised by the immune-mediated prothrombotic condition.

Acute Disease↗
PubMed2000

Cyclin E expression, a potential prognostic marker for non-small cell lung cancers.

Cyclin E is a G1 cyclin that has been shown to be one of the key regulators of the G1-S transition and could consequently be a deregulated molecule in tumors. In the present study, we have characterized cyclin E expression by immunohistochemistry in 217 resected non-small cell lung cancers (NSCLCs) and found large variations in cyclin E expression among tumors. High-level cyclin E expression (a cyclin E-labeling index > or =30%), observed in 115 (53%) of 217 NSCLCs, was more frequently found in tumors from smokers than from nonsmokers (P = 0.001), in squamous cell carcinomas than in nonsquamous cell carcinomas (P = 0.0002), and in pT2-4 tumors than in pT1 tumors (P = 0.04) by the chi2 test. Multivariate logistic regression analysis for the correlation between cyclin E expression and various characteristics showed a significant association of high-level cyclin E expression with squamous cell carcinomas (P = 0.005). Patients with tumors having high-level cyclin E expression survived a significantly shorter time than patients with tumors having low-level expression, both among the 151 patients with potentially curatively resected NSCLCs (5-year survival rates, 48 and 63%, respectively; P = 0.03) and the 103 patients with p stage I NSCLCs (5-year survival rates, 57 and 81%, respectively; P = 0.007). High-level cyclin E expression was also a significant and independent unfavorable prognostic factor in both patients with potentially curatively resected NSCLCs (P = 0.01) and in those with p stage I NSCLCs (P = 0.03) by Cox's proportional hazards model analysis. These findings indicate that cyclin E may play a pivotal role for the biological behavior of NSCLCs, and that a high level of cyclin E expression may be a new prognostic marker for NSCLCs.

Aged↗
PubMed2000

[The outline of the general rule for clinical and pathological record of lung cancer].

In 1999, the Japan Lung Cancer Society published the fifth Japanese edition of the General Rule for Clinical and Pathological Record of Lung Cancer. According to the new UICC's TNM classification revised in 1997, the TNM classification of this General Rule was modified. The guide to taking good conventional and high resolution chest computed tomogram was showed. The types of bronchoscopic findings was simplified. In operative procedures, curability of surgical resection was divided into only two groups: complete resection and incomplete resection. Although WHO/IASLC histological classification was revised in 1999, the histological classification hasn't been modified yet in this new edition of General rule. It will be changed in the next version.

Bronchoscopy↗
PubMed2000

Prognostic significance of p27KIP1 protein and ki-67 growth fraction in non-small cell lung cancers.

We immunohistochemically examined specimens of 215 surgically resected non-small cell lung cancers (NSCLCs) for p27KIP1 protein (p27) expression and the growth fraction determined by the Ki-67 labeling index (LI). The NSCLCs analyzed showed considerable heterogeneity in both p27 and Ki-67 LIs; 25 of 207 (13%) lacked p27 expression (p27 LI < 5%), and 116 of 215 (54%) showed a high Ki-67 LI (>30%). The p27 LI was not significantly associated with the Ki-67 LI. A chi2 test showed that loss of p27 expression was inversely correlated with smoking (P = 0.01) and that a high Ki-67 LI was significantly associated with male gender, squamous cell carcinoma histology, and smoking (P < 0.0001 each). Prognostic values of p27 and Ki-67 expression were evaluated in 109 tumors of postsurgical pathological stages I and II. Patients with tumors lacking p27 expression survived for a significantly shorter time than patients with tumors expressing p27 (5-year survival rates, 38% and 68%, respectively; P = 0.02). Patients with tumors having a high Ki-67 LI survived for a significantly shorter time than patients with tumors having a low Ki-67 LI (5-year survival rates, 48% and 78%, respectively; P = 0.005). Multivariate analysis showed that loss of p27 expression tended to be an unfavorable prognostic factor (P = 0.054), whereas a high Ki-67 LI was a significant and independent unfavorable prognostic factor (P = 0.004). When analyzed by cell types, loss of p27 expression was a significant and independent unfavorable prognostic factor in squamous cell carcinomas (P = 0.01), whereas a high Ki-67 LI was a significant and independent unfavorable prognostic factor in nonsquamous cell carcinomas (P = 0.007). We further evaluated the importance of p27 expression in clinical outcome in combination with the Ki-67 LI and ras p21 protein (ras) expression, which we previously reported as an important prognostic factor in NSCLCs. Patients with tumors lacking p27 expression and having a high Ki-67 LI survived for a significantly shorter time than those with tumors expressing p27 and having a high Ki-67 LI (5-year survival rates, 17% and 52%, respectively; P = 0.003). Patients with p27-negative and ras-positive tumors survived for a significantly shorter time than those with both p27- and ras-positive tumors (5-year survival rates, 0% and 38%, respectively; P < 0.0001). These results indicate the pivotal roles of p27 and Ki-67 expression in the clinical outcome of NSCLCs.

Adult↗
PubMed1999

Effect of nitric oxide donors and nitric oxide synthase inhibitors in neonatal rat endotoxic shock.

Previous studies have shown an increased mortality in response to endotoxin in 24-hr-old neonatal rats compared with older neonates and adults. This increased susceptibility may be related to increased nitric oxide (NO) and thromboxane (TxB2) production. Twenty-four-hour-old neonatal rat pups were given either N(G)-nitro-L-arginine methyl ester (L-NAME; a nonspecific NO synthase inhibitor), S-methylthioisourea (SMT; a specific NO synthase inhibitor), or molsidomine (a NO donor) subcutaneously prior to or after an LD50 of intracardiac endotoxin. Mortality was followed for 72 hr. There was no statistically significant difference in mortality between control animals and those pretreated with L-NAME, SMT, or molsidomine. A trend toward increased mortality with nonspecific NO synthase inhibition and decreased mortality with the NO donor was noted. Splenic cells were obtained for in vitro cytokine stimulation studies. In vitro adherent splenic cell stimulation studies confirmed an increase in NO production with NO donor pretreatment and decreased production of NO with NO synthase inhibition pretreatment. There was no difference in TxB2 production with either the NO synthase inhibitor or the NO donor. In conclusion, at the several doses employed, neither nonselective or selective NO synthase inhibitors nor NO donors prevented endotoxin-induced mortality in rat neonatal shock. Although these findings do not preclude possible involvement of NO in neonatal pathophysiology, increased NO production thus does not appear to be the primary determinant of the increased susceptibility of the neonatal rat to endotoxic shock.

Animals↗
PubMed1999

Fine-needle aspiration cytology of malignant hemangiopericytoma of the salivary gland: A case report.

A 79-yr-old woman presented with a 5-yr history of swelling of the left cheek. The fine-needle aspiration (FNA) smear showed a spindle-cell neoplasm with capillaries and benign endothelial cells. The spindle cells possessed pleomorphic, hyperchromatic elongated nuclei and a moderate amount of ill-defined cytoplasm. They also showed papillary arcades surrounded and encased by relatively small ovoid to short spindle cells. Subsequent surgical excision confirmed the presence of malignant hemangiopericytoma (HP). Immunohistochemical studies on the histologic section using vimentin were strongly positive, consistent with HP. To the best of our knowledge, this is the second published report of FNA cellular features of malignant HP of the salivary gland. Besides delineating the FNA cellular features of HP of the salivary gland, the present case illustrates the value of using immunohistochemical approaches. Diagn. Cytopathol. 1999;21:398-401.

Aged↗