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Biomedical subjects

Kenji Suzuki

Publications and source records attributed to Kenji Suzuki.

At least 55 records · Page 3Linked to original sources

Left pneumonectomy for lung cancer after correction of contralateral partial anomalous pulmonary venous return.

We report the successful treatment of a 48-year-old man with left lung cancer and contralateral partial anomalous pulmonary venous return (PAPVR). He was found to have an abnormal shadow on a regular checkup. Sputum cytology revealed squamous cell carcinoma. Chest computed tomography showed not only a left hilar mass but also showed that his right superior pulmonary vein was draining into the high portion of the superior vena cava. In the presence of the right partial anomalous pulmonary venous return, it was believed that left pneumonectomy would cause serious postoperative heart failure due to an increase in the left-to-right shunt. Therefore his partial anomalous pulmonary venous return was corrected first under cardiopulmonary bypass, and 3 weeks later he underwent successful radical left pneumonectomy.

Carcinoma, Squamous Cell↗

Problems in diagnosis and surgical management of clinical N1 non-small cell lung cancer.

BACKGROUND: Clinical diagnosis of the nodal status is a significant factor in determining the treatment and predicting the prognosis in lung cancer patients. A patient with clinical N1 (cN1) disease is usually considered to be a candidate for surgical intervention in the present staging system in non-small cell lung cancer (NSCLC). However, cN1 disease is a subset for which the method of treatment and surgical results are variable, simply because both upstaging and downstaging can occur. We evaluated the surgical and pathologic results of cN1 NSCLC patients to reveal the problems in diagnosis and surgical management for this subset. METHODS: From January 1998 to March 2003, 1,606 patients underwent thoracotomy for primary lung cancer at the National Cancer Center Hospital. Among them, the subjects for this study were 168 (10.5%) NSCLC patients who were clinically diagnosed as having N1 disease and underwent surgery without induction therapy. RESULTS: The tumor cell types of these 168 cN1 NSCLC patients were adenocarcinoma in 73 (44%) and squamous cell carcinoma in 79 (47%). Pneumonectomy was performed in 26% (n = 43) patients, bilobectomy in 15% (n = 25), and exploratory thoracotomy in 11% (n = 19). Of 19 exploratory thoracotomy cases, 10 cases were due to pleural dissemination. The pathologic nodal status of the 135 patients who underwent pulmonary resection and mediastinal dissection was pN0, 19% (n = 25); pN1, 44% (n = 59); and pN2-3, 37% (n = 51). Of the 55 adenocarcinomas, 60% (n = 33) were revealed to be N2 disease on pathologic examination. There were no significant differences in the serum tumor markers between the pN1 and pN2 groups. Among the 25 patients who were downstaged postoperatively (cN1-pN0), 21 patients (84%) showed obstructive pneumonia in the lung. CONCLUSIONS: In the staging process of cN1 disease, it will be helpful to perform mediastinoscopy and thoracoscopy to avoid unnecessary thoracotomy especially in adenocarcinoma, even though mediastinal nodes and pleural dissemination were negative on computed tomography investigation. Since extensive pulmonary resection (bilobectomy or pneumonectomy) was required in 41% of the patients, preoperative detailed cardiopulmonary function tests should be mandatory to reduce surgical morbidity and mortality. On the other hand, when pneumonia due to airway obstruction by the tumor exists, false-positive hilar nodes can be expected.

Adenocarcinoma↗

Phase II trial of postoperative adjuvant cisplatin and etoposide in patients with completely resected stage I-IIIa small cell lung cancer: the Japan Clinical Oncology Lung Cancer Study Group Trial (JCOG9101).

OBJECTIVE: Indications for surgical intervention for very limited small cell lung cancer have not yet been determined. The objective of this study is to determine whether resection followed by cisplatin and etoposide is feasible. METHODS: From September 1991 through December 1996, 62 patients with completely resected small cell lung cancer who were less than 76 years of age from 17 centers were entered in the trial. Of 62 patients, 61 were eligible, with a median follow-up of 65 months. Chemotherapy consisted of 4 cycles of cisplatin (100 mg/m 2 , day 1) and etoposide (100 mg/m 2 , days 1-3). There were 49 (80%) male patients, 44 with clinical stage I disease, 10 with stage II disease, and 6 with stage IIIa disease. RESULTS: Forty-two (69%) patients received 4 cycles of cisplatin and etoposide. No treatment-associated mortality was noted. Median survival time was not reached in patients with pathologic stage I disease, was 449 days in patients with stage II disease, and was 712 days in patients with stage IIIa disease. Three-year survival was 61% overall, 68% in patients with clinical stage I disease, 56% in patients with stage II disease, and 13% in patients with stage IIIa disease ( P = .02). Recurrence was noted in 26 (43%) patients overall. Local failure was noted in 6 (10%) patients. Locoregional recurrence tends to be found more frequently in patients with stage IIIA disease. Distant failure was found in 21 (34%) patients overall. Brain metastasis was found in 15% of the patients. CONCLUSION: Major lung resection followed by postoperative cisplatin and etoposide is feasible, with a favorable survival profile. Because nodal metastasis appears to be a major prognostic factor, preoperative evaluation of nodal status remains a major concern.

Adult↗

Computer-aided diagnosis in thoracic CT.

Computer-aided diagnosis (CAD) provides a computerized diagnostic result as a "second opinion" to assist radiologists in the diagnosis of various diseases by use of medical images. CAD has become a practical clinical approach in diagnostic radiology, although, at present, primarily in the area of detection of breast cancer in mammograms. Currently, a large research effort has been devoted to the detection and classification of various lung diseases in thoracic computed tomography (CT) images. We describe in this article the current status of the development of CAD schemes in thoracic CT, including nodule detection, distinction between benign and malignant nodules, and detection, characterization, and differential diagnosis of diffuse lung disease. Observer performance studies indicate that these CAD schemes would be useful in clinical practice by providing radiologists with computer output as a "second opinion."

Humans↗

COX-1 and COX-2 conversely promote and suppress ischemia-reperfusion gastric injury in mice.

OBJECTIVE: Neutrophil activation followed by free radical production is a feature that is common to the various forms of gastric injury. However, the roles of cyclooxygenase (COX)-1 and -2 in neutrophil activation have yet to be clarified in the gastric mucosa. We examined the roles of both COX-1 and COX-2 in neutrophil activation and free radical production in ischemia-reperfusion (IR) injury in the gastric mucosa of mice. MATERIAL AND METHODS: Ischemia was induced by clamping the celiac artery for 30 min, then removing the clamp for 90 min. SC-560, a selective COX-1 inhibitor; NS-398, a selective COX-2 inhibitor; or rebamipide, a mucoprotective agent, was administered to mice 60 min before ischemia. Gastric damage was evaluated histologically and by measuring myeloperoxidase (MPO) activity. Expressions of COX protein and intercellular adhesion molecule (ICAM)-1 were evaluated by Western blot analysis and ELISA, respectively. Effects of these drugs on thiobarbituric acid reactive substances (TBARS) and gastric blood flow were also evaluated. RESULTS: COX-2 expression was induced in gastric mucosa 60 min after reperfusion, whereas COX-1 expression remained unaltered. Localization of COX-1 and ICAM-1 in IR-injured mucosa was observed mainly in endothelial cells, while COX-2 expression was detected in mesenchymal cells such as mononuclear cells, spindle-like cells and endothelial cells. SC-560 significantly decreased gastric blood flow at the reperfusion point and reduced gastric mucosal injury in IR mice. Furthermore, SC-560 pretreatment significantly reduced MPO activity, TBARS levels and ICAM-1 expression. In contrast, NS-398 significantly increased ICAM-1 expression, MPO activity and TBARS levels, and aggravated gastric damage in IR mice. Rebamipide pretreatment reduced both COX-2 expression and IR injury. CONCLUSIONS: In IR mice, COX-2 protects the gastric mucosa by down-regulating ICAM-1 expression, whereas COX-1 is involved in up-regulating reperfusion flow, thereby aggravating the mucosa.

Alanine↗

Computer-aided diagnostic scheme for distinction between benign and malignant nodules in thoracic low-dose CT by use of massive training artificial neural network.

Low-dose helical computed tomography (LDCT) is being applied as a modality for lung cancer screening. It may be difficult, however, for radiologists to distinguish malignant from benign nodules in LDCT. Our purpose in this study was to develop a computer-aided diagnostic (CAD) scheme for distinction between benign and malignant nodules in LDCT scans by use of a massive training artificial neural network (MTANN). The MTANN is a trainable, highly nonlinear filter based on an artificial neural network. To distinguish malignant nodules from six different types of benign nodules, we developed multiple MTANNs (multi-MTANN) consisting of six expert MTANNs that are arranged in parallel. Each of the MTANNs was trained by use of input CT images and teaching images containing the estimate of the distribution for the "likelihood of being a malignant nodule," i.e., the teaching image for a malignant nodule contains a two-dimensional Gaussian distribution and that for a benign nodule contains zero. Each MTANN was trained independently with ten typical malignant nodules and ten benign nodules from each of the six types. The outputs of the six MTANNs were combined by use of an integration ANN such that the six types of benign nodules could be distinguished from malignant nodules. After training of the integration ANN, our scheme provided a value related to the "likelihood of malignancy" of a nodule, i.e., a higher value indicates a malignant nodule, and a lower value indicates a benign nodule. Our database consisted of 76 primary lung cancers in 73 patients and 413 benign nodules in 342 patients, which were obtained from a lung cancer screening program on 7847 screenees with LDCT for three years in Nagano, Japan. The performance of our scheme for distinction between benign and malignant nodules was evaluated by use of receiver operating characteristic (ROC) analysis. Our scheme achieved an Az (area under the ROC curve) value of 0.882 in a round-robin test. Our scheme correctly identified 100% (76/76) of malignant nodules as malignant, whereas 48% (200/413) of benign nodules were identified correctly as benign. Therefore, our scheme may be useful in assisting radiologists in the diagnosis of lung nodules in LDCT.

Algorithms↗

Autonomic modulation of sinus and atrioventricular nodes in premature low-birth-weight infants.

Respiratory vagal activity is expressed by heart rate variability (HRV) at approximately 1 month of age in premature low-birth-weight infants (PLBWI). However, the autonomic inputs into the sinus node (SAN) and atrioventricular node (AVN) in PLBWI are unclear. We evaluated the variability in PP and PR intervals at day zero (day 0) and 1 month (1 month) after birth in 16 PLBWI (gestation 32.3 +/- 1.3 weeks, birth weight 1.578 +/- 257 g). The polygraph was recorded during sleep on day 0 and at 1 month. PP and PR intervals and the number of respiratory cycles were measured, and frequency analysis was performed by auto-correlation fast Fourier transforms. Power spectral density (PSD: ms(2)) was calculated for the low frequency domain (LF: 0.036 approximately 0.146 Hz), high frequency domain (HF: 0.146 approximately 0.390 Hz), total frequency (TF: 0.036 approximately 2.000 Hz), and respiratory sinus arrhythmia (RSA: frequency bandwidth of 0.3 Hz with peak respiratory frequency as median), and the PSD ratio in the PP and PR intervals (LF/HF, RSA/TF) were compared. Compared with day 0, a decrease in the LF/HF ratio and an increase in the RSA/TF ratio in PP intervals were observed at 1 month, consistent with expression of respiratory vagal activity. For PR intervals, on the other hand, the LF/HF ratio increased, indicative of accentuated sympathetic activity. However, the respiratory vagal input was weak, and the RSA/TF ratio remained unchanged. These observations suggest that, in PLBWI at 1 month, AVN conduction was not predominatly influenced by respiratory-related vagal activity, but was controlled by autonomic regulation, independent of the SAN.

Atrioventricular Node↗

Investigation of psychophysical measure for evaluation of similar images for mammographic masses: preliminary results.

We investigated a psychophysical similarity measure for selection of images similar to those of unknown masses on mammograms, which may assist radiologists in the distinction between benign and malignant masses. Sixty pairs of masses were selected from 1445 mass images prepared for this study, which were obtained from the Digital Database for Screening Mammography by the University of South Florida. Five radiologists provided subjective similarity ratings for these 60 pairs of masses based on the overall impression for diagnosis. Radiologists' subjective ratings were marked on a continuous rating scale and quantified between 0 and 1, which correspond to pairs not similar at all and pairs almost identical, respectively. By use of the subjective ratings as "gold standard," similarity measures based on the Euclidean distance between pairs in feature space and the psychophysical measure were determined. For determination of the psychophysical similarity measure, an artificial neural network (ANN) was employed to learn the relationship between radiologists' average subjective similarity ratings and computer-extracted image features. To evaluate the usefulness of the similarity measures, the agreement with the radiologists' subjective similarity ratings was assessed in terms of correlation coefficients between the average subjective ratings and the similarity measures. A commonly used similarity measure based on the Euclidean distance was moderately correlated (r=0.644) with the radiologists' average subjective ratings, whereas the psychophysical measure by use of the ANN was highly correlated (r=0.798). The preliminary result indicates that a psychophysical similarity measure would be useful in the selection of images similar to those of unknown masses on mammograms.

Algorithms↗

Computer-aided detection of peripheral lung cancers missed at CT: ROC analyses without and with localization.

PURPOSE: To retrospectively evaluate whether a difference-image computer-aided detection (CAD) scheme can help radiologists detect peripheral lung cancers missed at low-dose computed tomography (CT). MATERIALS AND METHODS: Institutional review board approval and informed patient and observer consent were obtained. Seventeen patients (eight men and nine women; mean age, 60 years) with a missed peripheral lung cancer and 10 control subjects (five men and five women; mean age, 63 years) without cancer at low-dose CT were included in an observer study. Fourteen radiologists were divided into two groups on the basis of different image display formats: Six radiologists (group 1) reviewed CT scans with a multiformat display, and eight radiologists (group 2) reviewed images with a "stacked" cine-mode display. The radiologists, first without and then with the CAD scheme, indicated their confidence level regarding the presence (or absence) of cancer and the most likely position of a lesion on each CT scan. Receiver operating characteristic (ROC) curves were calculated without and with localization to evaluate the observers' performance. RESULTS: With the CAD scheme, the average area under the ROC curve improved from 0.763 to 0.854 for all radiologists (P = .002), from 0.757 to 0.862 for group 1 (P = .04), and from 0.768 to 0.848 for group 2 (P = .01). The average sensitivity in the detection of 17 cancers improved from 52% (124 of 238 observations) to 68% (163 of 238 observations) for all radiologists (P < .001), from 49% (50 of 102 observations) to 71% (72 of 102 observations) for group 1 (P = .02), and from 54% (74 of 136 observations) to 67% (91 of 136 observations) for group 2 (P = .006). The localization ROC curve also improved. CONCLUSION: Lung cancers missed at low-dose CT were very difficult to detect, even in an observer study. The use of CAD, however, can improve radiologists' performance in the detection of these subtle cancers.

Aged↗

Inhibition of poly (ADP-ribose) synthetase improves pulmonary arterial endothelium-dependent relaxation after ischemic-reperfusion injury of splanchnic artery in rats.

The role of poly (adenosine diphosphate-ribose) synthetase (PARS) in the contractile and relaxant responses of pulmonary arteries injured by ischemia and reperfusion (IR) of splanchnic artery has not been evaluated. We examined these responses by using 3-aminobenzamide, a pharmacological inhibitor of PARS. IR models in rats were induced by clamping the superior mesenteric artery for 60 min, followed by release of the clamp for 60 min. In the 2 treated groups, 5 or 10 mg/kg of 3-aminobenzamide was administered as an IV bolus at 10 min before reperfusion, followed by infusion rates of 5 and 10 mg.kg(-1).h(-1), respectively, during the period of reperfusion (IR + PARS inhibitor 5 and 10 groups). In the vehicle-treated group, 3-aminobenzamide was not given, but IV saline was administered (IR group). In the control group, surgery was performed, but the superior mesenteric artery was not occluded (sham group). The pulmonary arteries were isolated, and effects of drugs were evaluated in vitro. The IR group showed no attenuation of the contractile responses of the pulmonary artery to phenylephrine. The relaxant responses to endothelium-dependent vasodilators, acetylcholine, and A23187 in the IR group were significantly inhibited when compared with the sham group. The reduction in the relaxant response to endothelium-dependent vasodilators was improved in the IR + PARS inhibitor 5 and 10 groups when compared with the IR group. We concluded that IR attenuated the relaxant responses of the pulmonary artery to endothelium-dependent vasodilators and that PARS inhibitors ameliorate the reduction in the relaxant response.

Acetylcholine↗

Discovery of a novel and potent human and rat beta3-adrenergic receptor agonist, [3-[(2R)-[[(2R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H-indol-7-yloxy]acetic acid.

In search for potent and selective beta3-adrenergic receptor (beta3-AR) agonists as potential drugs for the treatment of type II diabetes and obesity, a novel series of 1-(3-chlorophenyl)-2-aminoethanol derivatives were prepared and evaluated for their biological activity at human beta1-, beta2-, and beta3-ARs and rat beta3-AR expressed in Chinese hamster ovary (CHO) cells. Replacement of the right-hand side (RHS, benzene ring) in the 'first generation' beta3-AR agonists BRL 37344 and CL 316243 with a 1H-indole ring gave compound 31 with unique pharmacological properties among beta3-AR agonists. Initial in vitro assays showed that 31 possesses modest rat and human beta3-ARs agonistic activity. Introduction of various substituent into the indole nucleus of 31 afforded a number of compounds with good beta3-ARs agonistic activity. In particular, 90 having a carboxylic acid functionality at the 7-position of the indole nucleus showed the most potent human beta3-AR agonistic activity. Finally, optical resolution of 90 led to the identification of the most promising compound, [3-[(2R)-[[(2R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H-indol-7-yloxy]acetic acid (96, AJ-9677). This compound exhibited potent human beta3-AR agonistic activity (EC50=0.062 nM, IA=116%) with 210- and 103-fold selectivity over human beta2-AR and beta1-AR, respectively. Compound 96 also exhibited potent rat beta3-AR agonistic activity (EC50=0.016 nM, IA=110%). Moreover, repeated oral administration of 96 inhibited body weight gain and significantly decreased glucose, insulin, free fatty acid, and triglyceride concentrations in plasma in KK-Ay/Ta mice. On the basis of this pharmacological profile, 96 entered clinical development as a drug for the treatment of type II diabetes and obesity.

Acetates↗

Isolation of a new antibiotic, alaremycin, structurally related to 5-aminolevulinic acid from Streptomyces sp. A012304.

A new antibiotic, which is structurally related to 5-aminolevulinic acid, a precursor of heme biosynthesis, and named alaremycin, was isolated from the culture broth of an actinomycete strain through a random screening with the blue assay to detect the formation of anucleate cells in Escherichia coli. The producing strain was identified as Streptomyces sp. by morphological, physiological, chemical and genetic criteria. Alaremycin was purified from the culture supernatant by HP-20 hydrophobic-interaction chromatography, sequential solvent/water extraction in the acidic or alkaline pH range, and QMA cation-exchange chromatography. The chemical structure of alaremycin was determined as 5-acetamido-4-oxo-5-hexenoic acid by analyses of mass and NMR spectra. The antibacterial activity of alaremycin was enhanced in the presence of 5-aminolevulinic acid.

Aminocaproates↗

Metabolic syndrome and risk of isolated ST-T abnormalities and type 2 diabetes in Japanese male office workers.

Using a modified National Cholesterol Education Program (NCEP) definition of the metabolic syndrome (MS) with body mass index instead of waist circumference, we examined the associations of the MS with the risk of developing ST-T abnormalities in 3405 Japanese men aged 35-59 yr who did not have a history of cardiovascular disease or ST-T abnormalities. Of 3405 participants, 3166 men without type 2 diabetes (as diagnosed with the revised criteria of American Diabetes Association) also constituted a non-diabetic cohort. Examinations including electrocardiogram and fasting plasma glucose were repeated annually for 7 subsequent years. The subjects were classified as having ST-T abnormalities or type 2 diabetes when evidence of either of these disorders was found during at least 2 consecutive annual examinations. After adjustment for potential risk factors, the relative risks of ST-T abnormalities were 1.0 (referent), 2.66, 3.07, 4.27, and 8.40 for the presence of 0, 1, 2, 3, and > or =24 components of the MS, respectively (P for trend <0.001). The corresponding results for the risk of type 2 diabetes were 1.0 (referent), 3.49, 7.45, 15.00, and 24.04 (P for trend <0.001). The estimated incident rates for men in the low-WBC count (<7.3 x 10(9) cells/L)/no MS, high-WBC count (> or =7.3 x 10(9) cells/L)/no MS, low-WBC count/yes MS, and high-WBC count/yes MS were 3.4%, 4.6%, 7.4%, and 13.1% for ST-T abnormalities, respectively and were 3.6%, 7.1%, 18.0%, and 27.2% for type 2 diabetes, respectively. The respective multivariate-adjusted relative risks were 1.0 (referent), 1.26, 2.07, and 3.45 for ST-T abnormalities and were 1.0 (referent), 1.75, 5.14, and 6.90 for type 2 diabetes. A modified NCEP MS definition predicts ST-T abnormalities and type 2 diabetes. WBC count adds clinically important information to new-onset ST-T abnormalities and type 2 diabetes.

Arrhythmias, Cardiac↗

Cigarette smoking and the risk of the metabolic syndrome in middle-aged Japanese male office workers.

To examine the association between cigarette smoking and the risk of the metabolic syndrome (MS), 3649 Japanese male office workers aged 35-59 yr who did not have a history of cardiovascular disease were enrolled in this study. 2994 men without the MS at entry were followed up over a 7-yr period. A modified National Cholesterol Education Program definition with body mass index instead of waist circumference was used for the MS. With adjustment for age, family history of diabetes, alcohol intake, and regular physical activity, the odds ratios of the MS were 1.0 (referent), 1.30 (95% confidence interval (CI), 1.00-1.68), 1.07 (95% CI, 0.82-1.39), 1.17 (95% CI, 0.88-1.56), and 1.66 (95% CI, 1.24-2.20) for never smokers, ex-smokers, and those who smoked 1-20 cigarettes/d, 21-30 cigarettes/d, and > or =31 cigarettes/d, respectively (P for trend for current smokers only =0.006). As for the risk of developing the MS, the respective multivariate-adjusted hazard ratios of developing the MS were 1.0 (referent), 1.43 (95% CI, 1.14-1.79), 1.14 (95% CI, 0.91-1.44), 1.45 (95% CI, 1.14-1.84), and 1.59 (95% CI, 1.24-2.05) (P for trend for current smokers only =0.001). Among men without the MS at entry, body weight gain over 7 yr, compared with never smokers, was significantly higher in smokers who quit smoking. It is important for the prevention of the MS not only to quit smoking but also to prevent weight gain after smoking cessation.

Adult↗

3D-CT arteriography and 3D-CT venography: the separate demonstration of arterial-phase and venous-phase on 3D-CT angiography in a single procedure.

Although 3D-CT angiography provides valuable anatomic information regarding lesion and their surrounding vessels and bony structures, it cannot demonstrate lesions, arteries, and veins, separately. The separate demonstration of arterial-phase 3D-CT angiography (3D-CT arteriography) and venous-phase 3D-CT angiography (3D-CT venography) will facilitate the understanding of the vascular anatomy within lesions, thus, allowing improvement of diagnostic accuracy and potentially a safer surgical approach. We describe 3D-CT arteriography and 3D-CT venography by using a multidetector row helical CT.

Adult↗