Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 37 records · Page 2Linked to original sources

PubMed2001

Completely resected stage IIIA non-small cell lung cancer: the significance of primary tumor location and N2 station.

BACKGROUND: The number of N2 stations (single vs multiple N2 stations) is an important prognostic factor in patients with completely resected stage IIIA-N2 non-small cell lung cancer. However, the significance of both the N2 station(s) actually involved and the primary tumor location remains unclear. METHODS: The database was built with the use of a questionnaire survey on the survival of patients with pathologic stage IIIA-N2 non-small cell lung cancer completely resected between January 1992 and December 1993. The survey was performed by the Japan Clinical Oncology Group as of July 1999. The data include information on the survival and N2 stations of 402 patients. RESULTS: A frequently metastasized single N2 station was the lower pretracheal station in primary tumors in the right upper lobe, the subaortic station in the left upper lobe, and the subcarinal station in the right middle or lower lobe and the left lower lobe. In multiple N2 stations, the frequency of metastasis of the N2 station observed in a single N2 station was as high as 72% to 89%, and one or two other frequently metastasized stations were added to each group. Regarding the survival of patients with a primary tumor in each lobe except for the left lower lobe, a single N2 station resulted in a significantly better survival than did multiple N2 stations. Furthermore, the overall survivals classified according to each primary site showed a significant difference among the four primary sites (P =.04). CONCLUSIONS: The primary tumors in each lobe showed a prevalence of N2 station(s). The number of N2 stations is a good prognosticator except in patients with a primary tumor in the left lower lobe. In addition, the site of a primary tumor itself is also considered to influence the survival of the patients.

Adult↗

PubMed2001

Docosahexaenoic acid supplementation-increased oxidative damage in bone marrow DNA in aged rats and its relation to antioxidant vitamins.

We compared the influence of docosahexaenoic acid (DHA) supplementation on oxidative DNA damage in bone marrow between young and aged rats. As a marker of oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG) in DNA was analyzed. Young (5-week-old) and aged (100-week-old) female Wistar rats were given DHA (300mg/kg body weight/day) or vehicle (control) orally for 12 weeks. The 8-OHdG in the bone marrow in the aged DHA group was significantly higher than that in the other groups. Vitamin E concentrations, however, did not differ among the groups regardless of the DHA supplementation. Vitamin C (ascorbic acid) concentrations in the aged control group were approximately 1/2 those in the young control group. The concentrations of vitamin C tended to be higher in the young DHA group and lower in the aged DHA group when compared to their respective control groups. Changes in the concentrations of vitamin C and vitamin E in plasma were similar to those in the bone marrow. The activity of hepatic l-gulono- gamma -lactone oxidase, an enzyme responsible for vitamin C synthesis, corresponded well to the concentrations of vitamin C in the bone marrow and the plasma. These results suggest that in aged rats, but not young rats, excess supplementation of DHA induces oxidative DNA damage in bone marrow and that the decrease in vitamin C synthesis in aged rats is involved in the mechanisms of DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2001

cAmp signaling cascade: a promising role in ethanol tolerance and dependence.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Subhash C. Pandey and Toshikazu Saito. The presentations were (1) Action of ethanol on cAMP signaling pathways, by M. Yoshimura; (2) Alterations in the G protein adenylyl cyclase system and their mRNA levels in alcoholics, by H. Sohma; (3) The role of the CREB gene transcription factor in ethanol dependence and preference, by Subhash C. Pandey; and (4) The efficacy of adenylyl cyclase signal transduction to the nucleus in primary alcoholics, by M. E. Götz.

Alcoholism↗

PubMed2001

Recent research on alcohol tolerance and dependence.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hiroshi Suwaki and Harold Kalant. The presentations were (1) Influence of ADH genotypes on acute alcohol withdrawal syndrome in Japanese, by Susumu Higuchi; (2) Use of genetic analyses to refine phenotypes related to alcohol tolerance and dependence, by John C. Crabbe; (3) Neurochemical basis for alcohol dependence, by Seitaro Ohkuma and Masashi Katsura; (4) Adenylyl cyclase and development of tolerance to addictive drugs, by Masami Yoshimura; (5) Tolerance in rat lines selectively bred for alcohol preference, by Robert C. Stewart and Ting-Kai Li; and (6) Ethanol reinforcement, dependence, and vulnerability to relapse: Interactions between neuroadaptive and conditioning factors, by Friedbert Weiss.

Alcohol Dehydrogenase↗

PubMed2001

Glutathione attenuates coronary constriction to acetylcholine in patients with coronary spastic angina.

This study examined the effect of reduced glutathione (GSH), an important antioxidant that restores intracellular redox imbalance and prevents inactivation of endothelial-derived nitric oxide, on the abnormal vasomotor reactivity in spastic coronary arteries. The responses of epicardial diameter of the left coronary arteries to intracoronary infusion of acetylcholine (ACh; 50 microg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of GSH (50 mg/min for 6 min) or saline as a placebo in 24 patients with coronary spastic angina and in 28 control patients. All of the spastic coronary arteries showed constrictor response to ACh, whereas the control coronary arteries as a whole showed only minimal diameter changes to ACh. GSH infusion suppressed constrictor response of epicardial diameter to ACh in patients with coronary spastic angina, whereas it had no significant effect in control subjects. Saline infusion did not have any effects. The results indicate that GSH attenuated the constrictor response to ACh in epicardial coronary arteries of patients with coronary spastic angina. GSH may have an important role in the regulation of coronary vasomotor function in patients with coronary spastic angina.

Acetylcholine↗

PubMed2001

Inhibition of lung natural killer cell activity by smoking: the role of alveolar macrophages.

BACKGROUND: It is known that natural killer (NK) cell activity in the lung of smokers (SM) is lower than in non-smokers (NS). However, little is known about the underlying mechanisms. OBJECTIVE: The purpose of this work was to investigate the mechanisms of the inhibition of NK cell activity by alveolar macrophages (AM) in SM. METHODS: Lung effector cells and AM were obtained using bronchoalveolar lavage. The NK cell activity was assayed by 51Cr release method after incubation of 4 and 24 h, using K562 as target cell. AM were added at a concentration of 25% to effector cells. RESULTS: Following 24-hour culture, NK cell activity significantly increased in the NS but not in the SM. Lung NK cell activity was significantly augmented by interleukin-2 in the NS but not in the SM. Addition of AM to the NK cell preparation from SM exerted a significantly greater suppressive effect on autologous blood NK cell activity than in the NS. Indomethacin, catalase or thiourea did not prevent AM-mediated suppression of NK cell activity, in contrast to superoxide dismutase. CONCLUSIONS: These results suggest that the suppression of NK cell activity by AM in SM may be caused by O2- release rather than by prostaglandins, H2O2 or OH release from AM.

Adult↗

PubMed2001

Increased autoantibodies against oxidized low-density lipoprotein in coronary circulation in patients with coronary spastic angina.

Oxidized low-density lipoproteins are important in the progression of atherosclerosis. Autoantibodies against malondialdehyde-modified low-density lipoproteins have been reported to be predictive of the progression of atherosclerosis. This study sought to examine whether plasma levels of autoantibodies against oxidized low-density lipoprotein increase in the coronary circulation in patients with coronary spastic angina. The authors examined plasma antioxidized low-density lipoprotein antibody levels (activity unit values (AcU)/mL) simultaneously in the coronary sinus and the aortic root in 20 patients with coronary spastic angina, 23 patients with stable exertional angina, and 15 control subjects by measuring plasma levels of immunoglobulin G (IgG) autoantibodies against malondialdehyde-modified low-density lipoproteins by enzyme-linked immunosorbent assay. The plasma antioxidized low-density lipoprotein antibody levels (AcU/mL) in the coronary sinus increased in coronary spastic angina (38 +/- 16) compared with stable exertional angina (23 +/- 7) and control subjects (20 +/- 6) (p < or = 0.0001). The levels (AcU/mL) in the aortic root also increased in coronary spastic angina (33 +/- 12) compared with stable exertional angina (23 +/- 7) and control subjects (20 +/- 6) (p < 0.005). Furthermore, the coronary sinus-arterial differences of the levels (AcU/mL) were also higher in coronary spastic angina (5 +/- 9) than in stable exertional angina (0 +/- 6) and healthy subjects (-1 +/- 5) (p < 0.05). The generation of malondialdehyde-modified low-density lipoproteins is reported to be associated with atherothrombosis. These findings suggest that elevated levels of autoantibodies against malondialdehyde-modified oxidized low-density lipoproteins in coronary circulation are associated with the development of atherothrombosis from the progression of atherosclerosis rather than with the extent of coronary atherosclerosis in patients with coronary spastic angina.

Acetylcholine↗

PubMed2001

Nitric oxide-mediated vasodilatation is decreased in forearm resistance vessels in patients with coronary spastic angina.

It has been reported that coronary endothelial dysfunction is associated with the pathogenesis of coronary spasm, and that endothelial nitric oxide (NO) mediated vasodilatation was decreased in coronary epicardial arteries in patients with coronary spastic angina (CSA). However, there are few reports about the endothelial function in peripheral resistance vessels of patients with CSA, so the present study investigated the role of NO in forearm resistance vessels in such patients. The responses of forearm blood flow to acetylcholine (ACh; 8-24 microg/min) and sodium nitroprusside (SNP; 0.4-1.2 microg/ml) infusions was examined using plethysmography, and subsequently the responses to ACh after an infusion of N(G)-monomethyl-L-arginine (L-NMMA; 4 micromol/min, for 5 min) in 17 patients with CSA and 17 age- and sex- matched controls. The vasodilator responses to ACh and SNP were comparable between the 2 groups (p=NS). L-NMMA significantly suppressed the vasodilator responses to ACh in controls (p<0.05), but there was no significant difference in the responses to ACh before and after infusion of L-NMMA in patients with CSA (p=NS). These results indicate that endothelial NO-mediated vasodilatation is decreased in the forearm resistance vessels of patients with CSA.

Acetylcholine↗

PubMed2001

Pulmonary resection for metastases from colorectal cancer.

BACKGROUND: We reviewed our experience in the surgical treatment of 47 patients with colorectal pulmonary metastases and investigated factors affecting their survival. METHOD: From September 1986 to December 1999, 47 patients underwent 59 thoracotomies for pulmonary metastases from colorectal cancer. RESULTS: The median interval between colorectal resection and lung resection (disease-free interval [DFI]) was 33 months. Overall, 5-year survival was 48%. Five-year survival was 51% for patients with solitary metastasis (n = 30), 47% for patients with ipsilateral multiple metastases (n = 11), and 50% for patients with bilateral metastases (n = 6), and there were no significant differences. Five-year survival was 80.8% for 14 patients with DFI of < 2 years and 39.7% for 30 patients with a DFI of > 2 years (p = 0.22). Five-year survival for 11 patients with normal prethoracotomy carcinoembryonic antigen (CEA) levels was 70%, and that for 26 patients with elevated prethoracotomy CEA levels (> 5 ng/mL) was 36% (p < 0.05). Eight patients had extrathoracic disease. The median survival time after pulmonary resection was 18.5 months, and the 5-year survival was 60%. A second resection for recurrent metastases was performed in five patients, and a third resection was done in one patient. All six patients are alive. The median survival of five patients who underwent a second thoracotomy was 22 months (range, 2 to 68 months), and one patient is alive 39 months after the third resection. CONCLUSION: Pulmonary resection for metastases from colorectal cancer may help prolong survival in selected patients, even with bilateral lesions, recurrent metastasectomy, or extrathoracic disease. Prethoracotomy CEA level was found to be a significant prognostic factor.

Adult↗

PubMed2001

Lung cancer treated surgically in patients <50 years of age.

STUDY OBJECTIVES: Some investigators have suggested that lung cancer in young patients has a more aggressive course and a poorer prognosis than lung cancer in older patients. The aim of this study was to determine if the basal characteristics and survival in younger patients with lung cancer undergoing surgical resection differ from those of older patients. DESIGN: Retrospective clinical study. PATIENTS: Of 1,208 consecutive patients who underwent surgery for primary lung cancer between June 1984 and March 2000, we reviewed the medical records of 110 younger patients who were < 50 years of age at the time of surgery and compared them with 1,098 older patients (> or = 50 years of age). All deaths were included. RESULTS: In the younger patient group, asymptomatic disease and adenocarcinoma was significantly more frequent, the rate of smoking was significantly higher, and the amount of smoking (Brinkman index) was significantly larger. For the 94 younger patients with complete resection, the 5-year survival rate was 61.0%, which was not significantly higher than that for the 923 older patients (57.7%). However, the 53 younger patients with stage I disease (5-year survival of 84.3%) had significantly better survival than older patients with the same condition (71.6%). Survival of patients in stage II or stage III disease was not significantly different. CONCLUSION: The younger patients had significantly better prognoses, and a statistical difference was shown especially in the early stage, while in the advanced stage the malignancy of the lung cancer itself surpassed the difference in survival.

Adenocarcinoma↗

PubMed2001

Association of p53 gene mutation and telomerase activity in resectable non-small cell lung cancer.

PURPOSE: Mutation of the p53 gene and deregulation of telomerase may be essential for canceration in some malignant diseases. However, relationships between these occurrences have not yet been clarified. We examined the roles of p53 gene mutation and telomerase activity relative to the clinical and pathologic features of non-small cell lung carcinoma (NSCLC). METHODS: Frozen sections of 40 surgically resected NSCLC specimens were used. DNA extracted from fresh tumor specimens was analyzed with polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) method, to screen alterations in the p53 gene. Exons showing aberrant band shifts on SSCP were reamplified, and the PCR products were directly sequenced. In addition, the telomerase activity of the same specimens was analyzed quantitatively with the fluorescence-based telomeric repeat amplification protocol assay, and the total product generated (TPG) method. Clinical and pathologic parameters were evaluated using a statistical analysis system. RESULTS: Mutations of the p53 gene relevant to an altered protein were confirmed in 19 of 40 specimens (47.5%). The TPG of 40 specimens was 75.24 +/- 15.55 (mean +/- SE). The TPG of the 19 specimens positive for p53 gene mutation was significantly higher than that of the 21 specimens negative for p53 gene mutation. Furthermore, the degree of cell differentiation was significantly correlated with both p53 gene mutation and high telomerase activity. CONCLUSIONS: p53 gene mutation and high telomerase activity cooperate to induce tumorigenesis and low-grade differentiation in NSCLC. Simultaneous occurrence of p53 gene mutation and high telomerase activity may be relevant to the grade of malignancy in NSCLC.

Aged↗

PubMed2001

Increased plasminogen activator inhibitor activity and diabetes predict subsequent coronary events in patients with angina pectoris.

BACKGROUND: Plasminogen activator inhibitor (PAI) is a marker of recurrence of myocardial infarction. Diabetes mellitus is also an important risk factor of coronary artery disease, including myocardial infarction and angina pectoris. AIM: We examined baseline plasma PAI activity levels, clinical variables, and angiographic findings and assessed them as prospective values for subsequent coronary events, such as sudden death, nonfatal myocardial infarction and coronary revascularization by percutaneous transluminal coronary angioplasty or coronary artery bypass surgery during the follow-up period. METHODS: We conducted a prospective study for 4 years of 249 consecutive patients admitted with angina pectoris. Blood samples for PAI were drawn at discharge. RESULTS: In the multivariate Cox proportional hazard model, PAI activity and diabetes mellitus were significant and independent risk factors (the risk increased by 10% in those with a higher PAI concentration and by 70% in diabetic patients). Event-free survival was reduced by higher PAI activity (> or = 8.4 IU/mL) and the presence of diabetes. The patients with higher PAI activity and diabetes had a 4.2-fold risk in comparison with the patients with lower PAI activity and no diabetes. However, patients with lower PAI activity were less likely to have coronary events even when they had diabetes. CONCLUSIONS: Higher PAI activity and diabetes predict subsequent coronary events in patients with angina pectoris. Diabetes has less prognostic value for subsequent coronary events in patients with lower PAI activity.

Angina Pectoris↗

PubMed2001

Neuroprotective effect and intraocular penetration of nipradilol, a beta-blocker with nitric oxide donative action.

PURPOSE: To investigate the effect of nipradilol, an alpha(1),beta-blocker with a nitric oxide donative action, on N:-methyl-D-aspartate (NMDA)-induced retinal damage in rats and to determine whether topically instilled nipradilol penetrates the ipsilateral posterior retina-choroid at pharmacologically active concentrations in rabbits. METHODS: To determine effects on NMDA-induced damage, drugs were injected alone or with NMDA into the vitreous of one eye, and cell loss in the ganglion cell layer (GCL) and thinning of the retinal neural cell layers were histologically evaluated. To evaluate posterior penetration, first, [(14)C]-nipradilol was instilled, and its tissue concentration was measured. Second, nipradilol or timolol was instilled, and their effects on intravitreal injection of endothelin-1-induced retinal artery contraction were compared, to evaluate whether a pharmacologically active level of nipradilol penetrates the inner limiting layer by topical application. RESULTS: Intravitreous injection of NMDA reduced cell numbers in the GCL and the thickness of the inner plexiform layer (IPL) to 50.4% +/- 2.6% and 47.8% +/- 4.9% (n = 8) of control, respectively. Nipradilol alone had no effect. Coadministration of nipradilol with NMDA reduced cell numbers in the GCL and IPL thickness to 67.8% +/- 2.2% and 74.4% +/- 5.2% of control, respectively (P: < 0.05-0.01). Sodium nitroprusside, but not timolol or bunazosin, also significantly prevented the NMDA-induced reduction of cell numbers in the GCL and IPL thickness. Radioactivity of nipradilol was found in the ipsilateral posterior retina-choroid at 318.6 +/- 42.9 ng/g (n = 4), which was significantly higher than in the contralateral control (107.4 +/- 21.8 ng/g). Topical application of nipradilol, but not timolol, significantly suppressed the endothelin-1-induced contraction of the retinal artery (83.95% +/- 8.15% and 35.24% +/- 5.62% of baseline vessel diameter for nipradilol and timolol, respectively). CONCLUSIONS: Nipradilol suppressed the NMDA-induced retinal damage in rats for which nitric oxide released from nipradilol may be responsible. Posterior penetration studies suggested that an effective concentration of nipradilol reached the posterior retina after topical application.

Adrenergic alpha-Antagonists↗

PubMed2001

[Wedge resection for lung cancer].

The role of wedge resection in lung cancer is reviewed. In the past century, many reports appeared dealing with limited resection for lung cancer, and it is clear that wedge resection should be performed in patients who are considered at high risk for not tolerating lobectomy; still there is no prospective or even retrospective study on wedge resection carried out in candidates for lobectomy. In recent years, progress in imaging diagnostic technology using high-resolution computed tomography has increased the opportunity to diagnose early adenocarcinoma presenting as small ground-glass opacity (GGO) which could not be detected on chest radiographs. Some patients with GGO may become candidates for wedge resection in this century, if additional favorable data result from prospective studies relevant to imaging diagnosis, pathology, and prognosis.

Adenocarcinoma↗

PubMed2001

[Efficacy and toxicity of lenograstim (glycosylated recombinant human granulocyte-colony stimulating factor) on peripheral blood stem cell harvest in healthy donors].

Peripheral blood stem cell harvest with lenograstim (glycosylated rhG-CSF) was performed 12 times from 10 normal donors. Five micrograms/kg of lenograstim was administered subcutaneously twice a day (10 micrograms/kg/day) for 4 to 6 days, and apheresis was performed on day 5 to 7 depending on the collected CD 34+ cell counts. We collected a sufficient number of CD 34+ cells in 9 mobilizations from 7 donors less than 50 years of age, with a total number of collected CD 34+ cells in each mobilization of 22.1 +/- 6.5 x 10(7). In contrast, we could not obtain a sufficient number of CD 34+ cells in 2 mobilizations from 3 donors above 50 years of age, with a total number of collected CD 34+ cells of 9.8 +/- 3.3 x 10(7). Although all donors had adverse events in response to lenograstim administration, all of them were grade 2 or less toxicity. These results indicate that peripheral blood stem cell mobilization and apheresis by lenograstim is safe and well tolerated, but the risk of poor mobilization may become higher in donors more than 50 years of age.

Adjuvants, Immunologic↗

PubMed2001

[Experience of gamma-detecting probe for the survey of sentinel node in gastroesophageal malignancies].

Gamma-detecting probe NAVIGATOR GPS (Autosuture Japan) was evaluated by using of 99mTc. Linearlity of counting in radioactivity was fairly good, but the sensitivity of the prove is so low, that sentinel node (SN) should contain the 3.7 x 10(-3) MBq (0.1 microCi) of 99mTc or more for the most effective use of it. And the count rate of the gamma-detecting probe was influenced by the distance and angle from the 99mTc source variously. It is important for the operator to know such characteristics of the gamma-detecting probe in order to obtain the correct SN judging.

Esophageal Neoplasms↗

PubMed2001

Pathophysiological significance and clinical application of ANP and BNP in patients with heart failure.

Plasma levels of ANP and BNP increase in accordance with the severity of the heart failure. In severe cases, the amount of BNP secreted surpasses that of ANP. The main secretion site of BNP is the ventricles, and that of ANP is the atria. However, ANP is also secreted from the ventricles as heart failure advances, and thus the ventricles are important sites for both BNP and ANP. It is well known that myocardial stretch is a key factor in the stimulation of the secretion of ANP and BNP, although neurohumoral factors also play a role in the secretion mechanism. The major physiological effects of ANP and BNP are vasodilation, natriuresis, and inhibition of the renin-angiotensin-aldosterone (RAA) and the sympathetic nervous systems; all of which are supposed to suppress the progression of heart failure. The inhibitory action of ANP and BNP on the RAA system has been considered to be an extra-cardiac effect. We recently reported the activation of an angiotensin-converting enzyme and aldosterone production in failing human hearts. ANP and BNP, however, would inhibit aldosterone production, not only in the adrenal cortex but also in cardiac tissue. ANP, and especially BNP, are useful markers of the heart's status during treatment for heart failure. The infusion of synthetic ANP (hANP) or BNP (Nesiritide) is effective in the treatment of acute heart failure. In Japan, BNP occupies an important position in the diagnosis of chronic heart failure, as ANP does in the treatment of acute heart failure.

Animals↗

PubMed2000

The heart is a source of circulating cardiotrophin-1 in humans.

Cardiotrophin-1 (CT-1) is a new member of the interleukin (IL)-6 family of cytokines and one of the endogenous ligands for gp130 signaling pathways in the heart, which has potent hypertrophic and survival effects on cardiac myocytes. However, the clinical significance of CT-1 is poorly understood, mainly because there is no widely applicable specific and sensitive assay system for measuring plasma levels of circulating CT-1. We therefore developed a competitive radioimmunoassay (RIA) for human CT-1 with rabbit antiserum recognizing the N-terminus region of human CT-1 and using recombinant human CT-1 as a calibrator. The assay displays no cross-reactivities with any of the IL-6 family of cytokines including IL-11, leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. The lower detection limit in buffer was found to be 43 fmol/ml, and the working range was 120-8300 fmol/ml (CV < 15%). This RIA directly recognizes CT-1-like immunoreactivity in human plasma with a mean value of 571 +/- 75 fmol/ml (mean +/- SD) in healthy volunteers. The RIA coupled with gel filtration chromatographic analyses showed that the major molecular form of circulating CT-1 corresponds to recombinant full-length human CT-1. Moreover, there is a significant increase in the plasma CT-1 concentration from the aorta and coronary sinus, which clearly indicates that the heart secretes CT-1 via the coronary sinus into the peripheral circulation. This RIA should serve as a powerful tool for investigating the clinical significance of CT-1.

Adult↗