Biomedical subjects

Kenji Suzuki

Publications and source records attributed to Kenji Suzuki.

At least 109 records · Page 6Linked to original sources

PubMed2003

Gliclazide protects pancreatic beta-cells from damage by hydrogen peroxide.

Oxidative stress is induced under diabetic conditions and possibly causes various forms of tissue damage in patients with diabetes. Recently, it has become aware that susceptibility of pancreatic beta-cells to oxidative stress contributes to the progressive deterioration of beta-cell function in type 2 diabetes. A hypoglycemic sulfonylurea, gliclazide, is known to be a general free radical scavenger and its beneficial effects on diabetic complications have been documented. In the present study, we investigated whether gliclazide could protect pancreatic beta-cells from oxidative damage. One hundred and fifty microM hydrogen peroxide reduced viability of mouse MIN6 beta-cells to 29.3%. Addition of 2 microM gliclazide protected MIN6 cells from the cell death induced by H(2)O(2) to 55.9%. Glibenclamide, another widely used sulfonylurea, had no significant effects even at 10 microM. Nuclear chromatin staining analysis revealed that the preserved viability by gliclazide was due to inhibition of apoptosis. Hydrogen peroxide-induced expression of an anti-oxidative gene heme oxygenase-1 and stress genes A20 and p21(CIP1/WAF1), whose induction was suppressed by gliclazide. These results suggest that gliclazide reduces oxidative stress of beta-cells by H(2)O(2) probably due to its radical scavenging activity. Gliclazide may be effective in preventing beta-cells from the toxic action of reactive oxygen species in diabetes.

Animals↗

PubMed2003

Synthesis and structure-affinity relationships of novel N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl)pyridine-3-carboxamides with potent serotonin 5-HT3 and dopamine D2 receptor antagonistic activity.

A structurally original series of N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl)pyridine-3-carboxamides derived from the corresponding benzamide 5 were prepared and evaluated for their binding affinity for the dopamine D(2) and serotonin 5-HT(3) receptors using rat striatum and rat cortical membrane, respectively. Many of the synthesized pyridine-3-carboxamides exhibited nanomolar binding affinity for the serotonin 5-HT(3) receptor along with moderate to high binding affinity for the dopamine D(2) receptor. Introduction of the more lipophilic bromine atom and methylamino group at the 5- and 6-positions of the pyridine ring, respectively, enhanced the affinity for the dopamine D(2) receptor while keeping a potent serotonin 5-HT(3) receptor binding affinity. As a result of structure-affinity relationships, the 5-bromo-2-methoxy-6-methylaminopyridine-3-carboxamide 53 was selected as the most promising product showing a high binding affinity for both receptors. Compound 53 affinity for the dopamine D(2) and serotonin 5-HT(3) receptors was much more potent than that of metoclopramide (dopamine D(2) receptor; 23.3 nM vs 444 nM, serotonin 5-HT(3) receptor; 0.97 nM vs 228 nM). Optical resolution of the racemate 53 brought about a dramatic change in the pharmacological profile with (R)-53 exhibiting a strong affinity for both the dopamine D(2) and serotonin 5-HT(3) receptors, while the corresponding (S)-53 had a potent serotonin 5-HT(3) receptor binding affinity and a moderate dopamine D(2) receptor binding affinity. X-ray crystallographic study of (R)-53 revealed the existence of two energically stable conformers just like two mirror images. This may account for (R)-53 high affinity for both the dopamine D(2) and serotonin 5-HT(3) receptors. Pharmacologically, (R)-53 [AS-8112] showed a potent antagonistic activity for both the dopamine D(2) and serotonin 5-HT(3) receptors in vivo tests and dose-dependently inhibited both the incidence and frequency of emetic episodes induced by cisplatin (ferrets) and morphine (dogs) with ID(50) values of 27.1 microg/kg, po and 136 microg/kg, po, respectively. On the basis of this pharmacological profile, (R)-53 is now under further investigation as a potential broad antiemetic agent.

Animals↗

PubMed2003

Current status of bacterial resistance in the otolaryngology field: results from the Second Nationwide Survey in Japan.

The study reported here was a nationwide assessment of otitis media (466 patients with acute suppurative otitis media and 476 with chronic suppurative otitis media), sinusitis (447 with acute sinusitis and 426 with chronic sinusitis), acute tonsillitis (724 patients), and peritonsillar abscess (141 patients) performed between November 1998 and March 1999. Eighty university hospitals, 79 affiliated hospitals, and 103 general practitioners participated. Methicillin-resistant Staphylococcus aureus(MRSA) comprised 15.6% of the 786 isolated strains of S. aureus. MRSA was frequently detected in patients with suppurative otitis media, but was uncommon in those with acute tonsillitis or peritonsillar abscess, and it was more common in those who had already been treated than in those who had not, with a significant difference between the groups. Vancomycin (VCM) showed the highest antimicrobial activity against MRSA and no VCM resistance was detected. Penicillin-sensitive Streptococcus pneumoniae(PSSP), penicillin-intermediate-resistant S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP) accounted for 49.6%, 28.5%, and 21.9% of the 228 isolated strains of S. pneumoniae, respectively. PISP and PRSP were frequently detected in children aged 5 years or younger. beta-Lactamase was produced by 96 of the 100 strains (96%) of Moraxella (Branhamella) catarrhalis. The 281 strains of Haemophilus influenzae isolated consisted of 199 beta-lactamase-negative, ampicillin-sensitive (BLNASe) strains (70.8%), 65 beta-lactamase-negative ampicillin-resistant (BLNAR) strains (23.1%), and 17 beta-lactamase-producing strains (6.0%). BLNAR strains were frequently detected in pretreated patients. Of these 281 strains of H. influenzae, 214 had nontypable capsules. In conclusion, the major bacterial species showed resistance to beta-lactams, indicating that care should be taken when selecting an appropriate antimicrobial agent.

Adolescent↗

PubMed2003

The proportion of consolidation to ground-glass opacity on high resolution CT is a good predictor for distinguishing the population of non-invasive peripheral adenocarcinoma.

OBJECTIVE: If non-invasive lung carcinomas are distinguishable on computed tomography (CT), limited surgery can be indicated before operation as a radical procedure. The purpose of this study is to define high resolution CT (HRCT) findings that indicate pathologic T1N0M0 tumor without vessel invasion. PATIENTS AND METHODS: We reviewed HRCT findings and pathological specimens of 98 consecutive patients underwent lobectomy or pneumonectomy with systematic hilar and mediastinal lymph node dissection from January 1996 to October 1999 for 101 pulmonary peripheral adenocarcinomas smaller than 3cm in diameter on HRCT. A total of 101 consecutive surgically resected peripheral adenocarcinomas of the lung measuring 3.0cm or less in the maximum dimension on HRCT were examined both radiologically and histologically. All CT scans ware reviewed by three chest radiologists or pulmonologists. The following parameters were measured on HRCT: the greatest diameter of tumor on found on all CT cuts (Td), the greatest diameter of consolidation found on all CT cuts (Cdmax), and the greatest diameter of consolidation found on a particular CT cut (Cd). Consolidation to tumor size ratio at respective maximum dimensions was calculated as Cdmax/Td, and consolidation to tumor size ratio on the slice image with the maximum tumor dimension was calculated as Cd/Td. One pathologist reviewed all pathological specimens to determine the size of tumor, evidence of vessel invasion, etc. without any information of HRCT, and we compared CT findings with pathological findings. RESULTS: There was a statistically significant difference between tumors with pathologic T1N0M0 adenocarcinoma without vessel invasion (least invasive disease: LID) and tumors with lymph node involvement or vessel invasion (invasive disease: ID) in each parameter. However, only when tumors with Cdmax/Td smaller than 0.5 were selected as LID tumors, could ID tumors be eliminated from the LID group. Five-year survival rate of this population is 95.7%. CONCLUSION: Consolidation to tumor size ratio at respective maximum dimensions was the best predictor of non-invasive peripheral adenocarcinoma.

Adenocarcinoma↗

PubMed2003

A clinicopathological study of resected subcentimeter lung cancers: a favorable prognosis for ground glass opacity lesions.

BACKGROUND: Owing to the advent of refined chest computed tomography (CT) images with higher resolution and CT screening programs, more faint and smaller lung cancers are being discovered. These include small-sized lung cancers such as those with a subcentimeter diameter, which had never been picked up on the routine chest roentgenogram films. However their clinicopathological characteristics with special reference to the proper surgical mode are not fully described so far. METHODS: During a 10-year period from 1991 through 2000 a total of 1,769 lung tumors were resected at the National Cancer Center Hospital, Tokyo. According to the pathology files of these patients, 51 patients had a primary tumor with the diameter of 1 cm or less. Three tumors arising in the bronchial lumina of hilum with a squamous cell carcinoma histology were excluded and the remaining 48 tumors of peripheral origin were studied. The clinicopathological features were analyzed according to three types of appearance on high-resolution CT: non-solid ground glass opacity (GGO) type (n = 19); part-solid GGO type (n = 9); and solid type (n = 20). Non-solid GGO is made up of homogeneous moderate increased density on CT, which cannot obscure the bronchovascular structure, whereas partly solid GGO contains a mere solid part but did not exceed 50% of the whole area (n = 9). All other lesions were considered solid type. RESULTS: For the three types of lesions, the distribution of age and sex was similar with the average age of 61 years and an almost even distribution of male/female patients. Although 6 patients had symptoms, the symptoms were not associated with the nodule itself. Twenty-six patients (54%) were screen-detected (16 chest roentgenogram films and 10 CT scans) and the others were detected by incidentally taken chest roentgenogram film or CT for other reasons than nodules detected. Two squamous carcinomas were positive for sputum cytology. Preoperative cytologic/histologic diagnosis was given in 14 patients (29%). The histologic type of GGO lesion was bronchioloalveolar carcinoma in all 28 cases. In solid lesions, besides 16 adenocarcinomas 2 cases of squamous cell carcinoma, 1 case each of small cell carcinoma and carcinoid tumor was seen. Lymph node involvement was seen only in 3 patients with solid lesions (N1 in 2 patients, N2 in 1 patient). As for operative mode, the limited resection was performed for 15 GGO lesions (54%) and 4 solid lesions (20%). Tumor recurrence was seen in 2 patients with solid lesions-1 in bone and the other in locoregional lymph node, and the former died of disease. CONCLUSIONS: Among subcentimeter lung cancers, GGO lesions (both non-solid and part-solid) constitute true early lung cancers. Since they have minimal or no invasive growth, limited resection for cure is justified. Conversely the solid lesion had significant invasive features such as lymph node metastasis. Lobectomy should remain as the standard mode of surgery despite such small size.

Adenocarcinoma↗

PubMed2003

Thymoma: a clinicopathologic study based on the new World Health Organization classification.

OBJECTIVE: This study explored the relationship between the histologic subtype of thymoma according to the new World Health Organization histologic classification and the clinical findings, as well as the prognostic significance of the classification. METHODS: A total of 130 patients with thymoma, who underwent resection at the National Cancer Center Hospital, Tokyo, from 1962 to 2000, were studied retrospectively. The histologic subtype of thymoma was determined according to the new World Health Organization histologic classification. The stage was also determined according to a modified Masaoka's classification as stage I, II, III, IVa, or IVb. To determine the factors that may affect the prognosis of thymoma, a multivariate analysis with Cox's proportional hazards regression model was performed. RESULTS: The distribution of histologic subtype was type A (n = 18), type AB (n = 56), type B1 (n = 15), type B2 (n = 29), and type B3 (n = 12). A close correlation was seen between the histologic subtype and stage (P =.000). The overall survivals at 5 and 10 years were 92% and 91%, respectively. The 5- and 10-year survivals according to stage were 100% and 100% (stage I, n = 40; stage II, n = 54), 81% and 76% (stage III, n = 25), and 47% and 47% (stage IV, n = 11), respectively. The difference in survival between stage III and stage IV was significant (P =.000). Patients with type A or AB thymoma demonstrated a 100% survival at both 5 and 10 years. Recurrences were seen in 12 patients with complete resection. According to a multivariate analysis, tumor size (P =.001), completeness of resection (P =.002), histologic subtype (P =.011), and stage (P =.00) were significant prognostic factors. CONCLUSION: The World Health Organization histologic classification significantly correlated with the clinical stage. Tumor size, completeness of resection, histologic subtype, and stage predicted the prognosis of thymoma.

Adult↗

PubMed2003

Kinetic analysis of the development of pancreatic lesions in mice infected with a murine retrovirus.

Sjögren's syndrome (SjS)-like sialoadenitis and exocrine pancreatitis were induced in mice infected with LP-BM5 murine leukemia virus, which induces a severe immunodeficiency termed murine AIDS (MAIDS). All mice with MAIDS showed advancing cellular infiltration around the pancreatic ducts as well as systemic exocrinopathy. The primary target tissue of the pancreas was acinar cells, and the pancreatic islets were well preserved until a late phase of the disease. Immunofluorescence and flow cytometry demonstrated that CD4(+) T cells, Mac-1(+) cells, and B220(+) cells were major inflammatory components, and IFN-gamma and IL-10 were mainly detected on CD4(+) T and Mac-1(+) cells in the pancreas. Both Th1 and Th2 cells were found. TUNEL(+) apoptotic cells were mostly detected among pancreas-infiltrating cells. Fas ligand and TNF-alpha were also detected among pancreas-infiltrating cells, whereas Fas was rarely expressed in the pancreatic acinar cells. Thus, MAIDS mice could be valuable for analyzing the pathogenesis of autoimmune-related pancreatitis associated with SjS.

Animals↗

PubMed2003

Malignant glomus tumor of the lung.

Primary malignant glomus tumors of the lung are extremely rare, and to our knowledge, only three cases have been described to date. We report one such case in a 53-year-old man who presented with a persistent dry cough. Chest computed tomography scans demonstrated an irregularly shaped mass in the right lower lobe of the lung. Many small nodules were distributed from the main tumor to the periphery, along with bronchovascular bundles. Right lower lobectomy was performed under the diagnosis of lung tumor. The tumor was located in the proximal portion of the right lower lobe and extended along the pulmonary arteries. Histological examination revealed a sheet-like proliferation of epithelioid glomus cells and fascicles of spindle cells. The presence of increased mitotic activity, tumor necrosis and prominent intravascular invasion suggested malignancy. The tumor cells were immunoreactive for vimentin, calponin, h-caldesmon, and alpha-smooth muscle actin, which indicated definitive smooth muscle differentiation. We believe that this is the fourth reported case of malignant glomus tumor of the lung.

Actins↗

PubMed2003

Obesity and obstructive sleep apnea syndrome.

We investigated the influence of obesity on upper airway obstruction, especially the relationship between obesity and the type of obstruction. The site of obstruction was identified by means of endoscopic examination and dynamic MRI during sleep. Many obese patients have the circumferential type of obstruction.

Adult↗

PubMed2003

Laser midline glossectomy and lingual tonsillectomy as treatments for sleep apnea syndrome.

Preservation treatments for sleep respiratory disorders, such as the use of a dental device and the technique of nasal continuous positive air pressure, cause discomfort to the patient and are not radical treatments. Therefore, we performed operative therapy instead. Laser midline glossectomy was performed to treat constriction at the root of the tongue in 16 patients diagnosed with sleep apnea syndrome. We also tried lingual tonsil excision using the Harmonic Scalpel in three patients with stenosis at the base of the tongue.

Adult↗

PubMed2003

Comparison of the state of sleep in patients with sleep-disordered breathing before and after surgical treatment.

In 19 surgically treated patients with sleep-disordered breathing for whom electroencephalograms could be recorded before and after surgery, and in 10 patients who suffered from daytime lethargy as assessed using the Epworth Sleepiness Scale (ESS) score, correlations between the stages of sleep before surgery and the ESS score and apnea-hypopnea index (AHI) were evaluated, and changes in AHI and the stages of sleep after surgery were examined. Neither the preoperative severity of AHI nor the ESS score showed an association with the stages of sleep. The improvement in the quality of sleep tended to be greater as the percentage improvement in the ESS score increased.

Adult↗

PubMed2003

Endoscopic examination of obstructive sleep apnea syndrome patients during drug-induced sleep.

Sixty patients diagnosed with obstructive sleep apnea syndrome (OSAS) underwent uvulopalatopharyngoplasty (UPPP). The effects of surgery were studied based on endoscopic findings during drug-induced sleep and determination of the apnea-hypopnea index (AHI) before and after the operation. Changes in the form of the airway during sleep in the recumbent position were observed, and the role of upper airway endoscopy in the diagnosis and surgical treatment of OSAS was determined. The site of airway obstruction during sleep induced by i.v. injection of 10 mg of diazepam was classified into five types, and changes in AHI and the site of airway obstruction were compared before and after surgery. Changes in airway morphology during sleep in the supine and recumbent positions were also compared before surgery. The postoperative improvement rate was 74.4% for the soft palatal type of obstruction, 76.2% for the tonsillar type, 53.3% for the circumferential palatal type and 34.0% for the mixed type. Treatment produced excellent or good effects for the soft palatal and tonsillar types of obstruction. However, many patients with the circumferential palatal and mixed types of obstruction showed only some improvement or no change. Good airway morphology was maintained in the recumbent position by patients with the soft palatal type of obstruction. With the circumferential palatal and mixed types of obstruction, improvement can be expected from operations which include surgical treatment of the posterior pharyngeal wall or lateral funiculus, or with midline laser glossectomy. A good operative outcome can be predicted in patients showing improvement of apnea in the recumbent position preoperatively.

Adult↗

PubMed2003

Influence of sleep respiratory disturbance on nocturnal blood pressure.

We subjected 65 patients to overnight monitoring and continuous nocturnal blood pressure measurement in order to assess the influence of sleep apnea on the circulatory system. Thirty-one patients were compared before and after surgery. The severity of sleep apnea was classified by means of the apnea-hypopnea index (AHI), the duration of exposure to low-level oxygen [calculated as the desaturation time (DT)] and changes in blood pressure (BP). Before surgery, a significant correlation was noted between DT and changes in BP. Therefore, DT was considered useful for assessing the influence of sleep apnea on nocturnal BP. After surgery, an improvement in AHI of > 50% was noted in 19/31 patients (61.3%), a result comparable to that described in the literature. Improvements in DT and change in BP were > 50% in 21/31 (67.7%) and 14/ 31 (45.2%) patients, respectively. With regard to the severity of sleep apnea before surgery, AHI was > or = 50 and DT > or = 40% in 10 and 18 patients, respectively and 19 patients showed changes in BP of > or = 40 mmHg. After surgery, one, five and two patients, respectively, still showed these values. Thus, a beneficial effect of surgery was demonstrated.

Adult↗

PubMed2003

Application of lingual tonsillectomy to sleep apnea syndrome involving lingual tonsils.

In sleep apnea syndrome, surgical treatment is applied in obstructive-type cases and some mixed-type cases. If the obstructive part is in the root of the tongue, forward transfer of the tongue, lingual tonsillectomy and laser midline glossectomy are applied. In this study, we demonstrate the surgical technique of lingual tonsillectomy using an ultrasonic coagulating dissector (SonoSurg) with a blade tip shape developed in our department. We conclude that lingual tonsillectomy using SonoSurg, which we have frequently used, should be the first choice of treatment for snoring and sleep apnea caused by hypertrophy of the lingual tonsils from the viewpoints of effectiveness, prevention of hemorrhage, safety and handling.

Adult↗

PubMed2003

Comparison of surgery and nasal continuous positive airway pressure treatment for obstructive sleep apnea syndrome.

Uvulopalatopharyngoplasty (UPPP) and nasal continuous positive airway pressure (n-CPAP) are used for the treatment of obstructive sleep apnea syndrome (OSAS). Although OSAS results from an abnormality of the pharynx, very little research has been carried out regarding the selection of UPPP or n-CPAP according to the type of abnormality. We performed n-CPAP titration before and after surgery, compared the treatment methods and evaluated the effect of the medical therapy. A sleep polygraph was recorded on the first night of admission and patients diagnosed with OSAS underwent n-CPAP titration on the second night. The blocked region was identified by means of endoscopic examination. A couple of months after surgery, polysomnography was repeated to determine the effect of surgery and the pressure level during n-CPAP forpatients who showed < 50% improvement in the apnea-hypopnea index. The results of surgery were poor in cases revealed by endoscopy to have the circumferential type of obstruction, but good for the soft palate and tonsil types. When endoscopic examinations were performed in conjunction with n-CPAP, the treatment was observed to act on the pharynx and to expand the airway in all cases Combined medical treatments were effective in cases where n-CPAP alone was ineffective due to high pressure.

Adult↗

PubMed2003

Anatomy of oral respiration: morphology of the oral cavity and pharynx.

The anatomical states of the oral cavity and pharynx during mouth breathing in children with adenoid hypertrophy and in adults confirmed the speculation that mouth breathing is disadvantageous compared with nose breathing. In addition, comparison of the anatomical state between wakefulness and sleep in normal adults showed slight depression of the tongue root and slight narrowing of the oropharynx and hypopharynx during sleep. Obstructive sleep-disordered breathing occurs due to a variety of factors, such as paranasal sinus disease, tonsil and adenoid hypertrophy, hypertrophy and morphological abnormalities of the soft palate and palatine uvula, low-set soft palate, micrognathia, macroglossia, obesity and tongue root depression. Narrowing or obstruction of the middle pharynx and hypopharynx is more marked in patients with obstructive sleep-disordered breathing than in normal people and is especially marked during sleep. Therefore, morphological (i.e. anatomical) changes during mouth breathing may provide useful information for evaluating the pathology of snoring and sleep apnea.

Adenoids↗

PubMed2003

Obstructive sleep apnea syndrome in children.

Obstructive sleep apnea syndrome (OSAS) in children is often caused by obstruction of the upper airway due to hypertrophy of the adenoids and palatine tonsils. Between October 1988 and December 1991, 50 children (34 males, 16 females) visited our department due to attacks of sleep apnea and underwent adenotomy or adeno-tonsillectomy. Respiratory monitoring during sleep was performed before and after operation, and the usefulness of the surgery was evaluated. Before operation, 27/ 50 children (54.0%) were diagnosed as having OSAS. Their age distribution showed peaks at the ages of 4 and 5 years and the male:female ratio was 2:1. Concerning the degree of improvement in clinical symptoms after surgery, marked effects were observed in 40/50 patients (80.0%), moderate effects in 7 (14.0%) and slight effects in 3 (6.0%). Concerning the degree of improvement in the apnea index after surgery in the 27 patients with OSAS, marked effects were observed in 22 patients (81.50%), moderate effects in 2 (7.4%), slight effects in 1 (3.7%) and no change in 2 (7.4%).

Adenoidectomy↗

PubMed2003

Effects of nutrient and food intake on calcaneous bone mass among healthy Japanese women in the predelivery and postpartum periods.

OBJECTIVE: To clarify the dietary factors affecting change in calcaneous bone mass during the predelivery and postpartum periods in healthy Japanese women. METHODS: The calcaneous bone mass was measured as the osteo sono-assessment index (OSI) using the quantitative ultrasound method in 76 Japanese women who were pregnant between February and June 2000. These women subsequently experienced normal pregnancy and labor and could be followed until the sixth month after delivery at an obstetrics and gynecology clinic center located in metropolitan Tokyo. After the intraindividual changes in the OSI during the follow-up period were determined, the relationship between the OSI or OSI change from gestation to the postpartum period and the estimates of nutrient and food intake obtained using a 140-item semiquantitative food frequency questionnaire (FFQ) were analyzed using stepwise multiple regression analysis. RESULTS: Iron intake in gestation was a significant positive correlate with the percentage change in the OSI between week 36 of gestation and day 5 after delivery (p < 0.001) and that between week 36 of gestation and month 6 after delivery (p < 0.001) (partial regression coefficient of energy-adjusted iron intake, beta = 0.493 mg/day and 0.342 mg/day, respectively). Intake of vitamin D and fruits and vegetables during gestation and/or postpartum was positively associated with the OSI change from week 36 of gestation to the postdelivery stage, whereas the OSI change was inversely related to the intake of carotene, sodium chloride, and meat in the gestation or postpartum period. CONCLUSIONS: Sufficient intake of iron, vitamin D, or fruits and vegetables may be important for the preservation of bone mass after delivery.

Adult↗