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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 199 records · Page 11Linked to original sources
PubMed1998

Analysis of lobectomy for small peripheral lung cancer supports extended segmentectomy.

We reviewed the records of 53 patients who underwent lobectomy for peripheral non-small cell lung cancer under 2 cm in diameter and established a rationale for segmentectomy with intraoperative lymph nodes dissection (extended segmentectomy). Five patients (9.4%) had intrapulmonary metastases. Nodal status was N0 in 34 patients (64.2%), N1 in 7 (13.2%), and N2 in 12 (22.6%). Based on examination of intraoperative frozen sections, 31 patients lacking lymph node metastases and visceral pleural involvement could have been candidates for extended segmentectomy. Twenty-seven had stage I disease on postoperative examination of paraffin-embedded sections. Of the remaining 4 patients, 1 had involvement of intrapulmonary lymph nodes in the segment where the primary lesion originated. Another patient had involvement only at the first mediastinal lymph node level, representing a "skipping metastasis". The remaining 2 patients had no lymph node involvement, but had intrapulmonary metastases in the same segments as the primary lesion. We conclude that an extended segmentectomy may be as effective as lobectomy for treatment of peripheral non-small cell lung cancer under 2 cm in diameter without evident lymph node involvement.

Adult↗
PubMed1998

A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese.

Coronary spasm plays an important role in the pathogenesis of not only variant angina but also ischemic heart disease in general. However, the precise mechanism(s) by which coronary spasm occurs remains to be elucidated. Coronary spasm may arise from interactions between environmental and genetic factors. Endothelial-derived nitric oxide (NO) has been implicated in the control of vascular tone. We have recently shown that both basal and acetylcholine (ACh)-induced NO activities are impaired in the coronary arteries of patients with coronary spasm. The purpose of this study has been to elucidate the possible variants that occur in the coding region of the endothelial nitric oxide synthase (eNOS) gene and that may be associated with coronary spasm. After initial screening in the entire 26 coding regions of the eNOS gene, we found a missense Glu298Asp variant in exon 7 in patients with coronary spasm. We subsequently performed a larger scale study involving 113 patients with coronary spasm and 100 control subjects, who were all diagnosed by intracoronary injection of ACh. The analysis revealed a significant difference in the distribution of the variant between the coronary spasm group (21.2%) and control group (9.0%; P=0.014 for dominant effect). Thus, we have found the missense Glu298Asp variant in the eNOS gene by the analysis of its entire 26 coding regions. The variant is significantly associated with coronary spasm.

Adult↗
PubMed1998

Primary anastomosis of the trachea: management and pitfalls.

Twenty-four patients with tracheal lesions were managed by various procedures, including primary anastomosis in 16, tracheoplasty in 2, and a terminal tracheostomy in 6. The patients undergoing anastomosis included 4 with primary tumors, 7 with secondary tumors, and 5 with benign stricture. Except for 2 patients, there was no leakage or stenosis after a resection of from two to nine tracheal rings. There were 4 patients in whom the laryngeal nerve was paralyzed on one side prior to resection and then was sacrificed on the other side because of tumor involvement. Because of difficulty in swallowing, the outcome was not satisfactory in the 3 patients despite a good anastomosis. Cricotracheal anastomosis was performed in 3 patients, and thyrotracheal anastomosis in 1. Two patients in whom the trachea and esophagus communicated were treated using pedicled intercostal muscle grafts. Tracheal stenosis can be observed in various pathological conditions. Consequently, the optimal treatment varies from patient to patient according to the type of a disease, the location and extent of a disease, and the condition of the laryngeal nerve, while it is also important to carefully select the most appropriate anesthetic method, approach, and type of reconstruction.

Adolescent↗
PubMed1998

Proposal for reasonable mediastinal lymphadenectomy in bronchogenic carcinomas: role of subcarinal nodes in selective dissection.

OBJECTIVE: The aims of this study were to reveal the characteristics of skipping N2 lung cancer and to develop a more reasonable approach for dissecting mediastinal lymph nodes. METHODS: Of consecutive 956 patients who were operated on for primary lung cancer from 1986 through 1996, 760 (79.5%) had a diagnosis of non-small cell carcinoma and were subjected to complete resection of the tumor together with hilar and mediastinal lymphadenectomy. RESULTS: Of 141 patients with N2 disease, 53 (37.6%) had skipping metastases. Among 78 patients with N2 cancer of the upper lobe, 37 (47.4%) had skipping metastases affecting upper or aortic mediastinal nodes whereas none of them had skipping metastases affecting lower mediastinal nodes. Among 47 patients with N2 cancer of the lower lobe, 13 (27.7%) had skipping metastases affecting mediastinal nodes. Of these 13 patients, 11 (84.6%) had skipping metastases affecting the subcarinal node. The remaining 2 patients had a huge primary tumor. CONCLUSIONS: Dissection of the upper part of the mediastinum including the aortic regions should be performed regardless of the operative appearance when cancer is located in the upper lobe, but it is not required for lower lobe tumors with negative hilar and subcarinal nodes. Dissection of the subcarinal node in patients with an upper lobe tumor is not routinely needed when the nodes in both the hilum and upper mediastinum are intact. We consider that the subcarinal node is of significance and skipping metastases should be defined as metastases that skip the subcarinal node in addition to N1 nodes.

Adenocarcinoma↗
PubMed1998

Operative approach for multiple primary lung carcinomas.

Of 908 patients who underwent operation for primary lung cancer between January 1985 and June 1996, we considered 57 (6.3%) to have a second primary lung cancer, which was synchronous in 28 cases (3.1%) and metachronous in 29 cases (3.2%). Five-year survival for patients with synchronous and metachronous disease from initial treatment of cancer was 70.3% and 66.0%, respectively. Survival after the development of a metachronous lesion was 32.9% at 5 years. Sixteen of the synchronous second tumors (57%) were detected on preoperative radiography or bronchoscopy and 11 (39%) at the time of operation. Survival of patients at stage I or II from treatment of a synchronous lesion (p = 0.002) and of a metachronous second lesion (p = 0.028) was significantly better compared with those at stage III or IV. Therefore it is important to carefully examine a synchronous lesion before and during the operation of a primary lung cancer and to perform close follow-up surveillance for early detection of a metachronous lesion. In treating multiple lung carcinomas consideration should always be given to performing precise staging, aggressive operative approach for early stage, and oncologically sound parenchymal sparing procedures.

Actuarial Analysis↗
PubMed1998

Enhanced production of nitric oxide may be involved in acute hypotension during maintenance hemodialysis.

To investigate the possible involvement of endogenous nitric oxide (NO) in acute hypotension during maintenance hemodialysis, we measured the plasma concentration of the nitrate anion NO3-, a stable metabolite of NO, in 19 patients undergoing hemodialysis. We analyzed heart rate variability to estimate the relationship between autonomic nervous activity and NO production, low-frequency/high-frequency components (L/H) as a parameter of cardiac sympathetic activity, and high-frequency power as a parameter of cardiac vagal activity. Six patients developed severe hypotension (a change in mean blood pressure during dialysis > or = 20 mm Hg), four patients developed mild hypotension (a change in mean blood pressure < or = 19 mm Hg and > or = 1 mm Hg), and nine patients did not develop hypotension. The plasma levels of NO3- before dialysis were markedly elevated in the severely hypotensive group compared with the patients who showed no hypotension (566+/-122 micromol/L v 133+/-38 micromol/L; P < 0.01), and this difference disappeared midhemodialysis and after hemodialysis. The plasma concentration of NO3- before dialysis was significantly associated with both the change in mean blood pressure during dialysis (r= -0.735; P = 0.003) and the mean blood pressure after dialysis (r = -0.675; P = 0.0015). The L/H ratio was inhibited before or after dialysis in the severely hypotensive group compared with the nonhypotensive group, and hypotension during dialysis was correlated with the inhibited L/H ratio before (r = 0.784; P = 0.001) or after (r = 0.822; P = 0.001) dialysis. Plasma NO3- concentrations were correlated with the L/H ratio before (r = -0.553; P = .014) or after (r = -0.546; P = 0.015) dialysis. These results suggest that inhibited sympathetic activity is one of the causes of acute hypotension during dialysis, and the enhanced production of NO is involved in this inhibition of the sympathetic activity in patients having a hypotensive episode during dialysis. The plasma concentration of NO3- before dialysis may be a predictor of the risk of hypotension during dialysis in patients with end-stage renal disease.

Acute Disease↗
PubMed1998

Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction.

OBJECTIVES: We examined the possible association between the missense Glu298Asp variant of the endothelial nitric oxide synthase (eNOS) gene and myocardial infarction (MI). BACKGROUND: Endothelium-derived nitric oxide (NO) plays a key role in the regulation of vascular tone. Recently, we reported that a missense Glu298Asp variant in exon 7 of the eNOS gene is a possible genetic factor involved in the pathogenesis of coronary spasm. Endothelium-derived NO also has vasoprotective effects by suppressing platelet aggregation, leukocyte adhesion and smooth muscle cell proliferation. METHODS: We screened 285 patients with an MI and 607 control subjects in Kumamoto Prefecture, Japan. Genotypes were determined by polymerase chain reaction-restriction fragment-length polymorphism analysis. RESULTS: The frequency of the missense Glu298Asp variant was significantly higher in the MI group than in the control group (21.1% vs. 13.3%, p = 0.003, odds ratio 1.73 for the dominant effect of the eNOS T allele). Multiple logistic regression analysis showed that the missense Glu298Asp variant was an independent risk factor for MI, as was diabetes mellitus, hypertension, cigarette smoking, hypercholesterolemia and body mass index. CONCLUSIONS: There was a significant association of the missense Glu298Asp variant of the eNOS gene with MI. This marker-disease association may be due to the impaired effects of NO on the cardiovascular system: dysregulation of vascular tone, platelet aggregation and leukocyte adhesion and smooth muscle cell proliferation, all of which promote coronary atherosclerosis and thrombosis.

Adolescent↗
PubMed1998

Vitamin C attenuates abnormal vasomotor reactivity in spasm coronary arteries in patients with coronary spastic angina.

OBJECTIVES: This study sought to examine effect of vitamin C, an antioxidant, on the abnormal vasomotor reactivity in spasm coronary arteries. BACKGROUND: Oxygen free radicals generated in the arterial walls have been shown to cause endothelial vasomotor dysfunction. METHODS: Responses of the epicardial arterial diameters of the left coronary arteries to the intracoronary infusion of acetylcholine (ACh) (10 and 50 microg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of vitamin C (10 mg/min) or saline as a placebo in 32 patients with coronary spastic angina and in 34 control subjects. RESULTS: Vitamin C infusion suppressed the constrictor response of the epicardial diameter to ACh in spasm coronary arteries but had no significant effect in the control coronary arteries (percent change in distal diameter in response to 10 microg/min of ACh [constriction (-), dilation (+), mean +/- SEM] before vitamin C: -8.2 +/- 2.9% in spasm arteries, +8.4 +/- 2.9%* in control arteries; during vitamin C: +0.2 +/- 3.8%* in spasm arteries, +7.2 +/- 1.3%* in control arteries [*p < 0.01 vs. spasm arteries before vitamin CI). The coronary sinus-arterial difference in plasma thiobarbituric acid reactive substances during ACh infusion, an indicator of lipid peroxidation in coronary circulation, was higher in patients with coronary spastic angina than in control subjects (p < 0.01) but was suppressed in patients with coronary spastic angina to comparable levels in control subjects by combined infusion of vitamin C. Saline infusion had no effect. CONCLUSIONS: The results indicate that vitamin C attenuates vasomotor dysfunction in epicardial coronary arteries in patients with coronary spastic angina. Oxygen free radicals may at least in part play a role in the abnormal coronary vasomotor reactivity in response to ACh in spasm coronary arteries.

Acetylcholine↗
PubMed1998

Flow cytometric analysis of Thy-1 expression in myelodysplastic syndrome.

We analyzed the expression of Thy-1 (CD90) antigen on CD34+ bone marrow mononuclear cells (BMMNC) obtained from 25 patients with myelodysplastic syndrome (MDS) by two-color flow cytometry. Five of nine patients (55.6%) with refractory anemia with excess of blasts (RAEB) and two of 16 (12.5%) with RAEB in transformation (RAEB-t) showed more than 20% of Thy-1 expression of their CD34+ BMMNC. Regarding chromosomal abnormalities, -5/5q- or -18 might be correlated with the expression of Thy-1 on CD34+ BMMNC in MDS. Nine patients were analyzed twice, once before and once after leukemic transformation and showed no significant change in Thy-1 expression. These results show that Thy-1 was expressed on CD34+ BMMNC in certain patients with MDS before leukemic transformation and that it was maintained during the disease progression. In contrast, expression of Thy-1 did not seem essential to the leukemic transformation in MDS though the patients with high Thy-1 expression might have poorer prognosis compared with those with low Thy-1 expression.

Adolescent↗
PubMed1998

Growth stimulation of non-small cell lung cancer xenografts by granulocyte-macrophage colony-stimulating factor (GM-CSF).

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been suggested to be involved in the carcinogenesis of some types of tumours by autocrine or paracrine mechanisms. We examined GM-CSF/GM-CSF receptor (GM-CSFR) gene expression in 20 human non-small cell lung cancer (NSCLC) xenografts. The stimulatory effects of GM-CSF were examined using GM-CSF transgenic severe combined immunodeficient (SCID) mice (GM-Tg-SCID), which produce abundant human GM-CSF. A NSCLC xenograft (LC11-JCK), expressed GM-CSFR but not GM-CSF, and showed more rapid growth in GM-Tg-SCID than non-GM-CSF transgenic SCID mice (non-Tg-SCID). GM-CSF gene expression was detected in 48 of 90 (53%) primary NSCLC human specimens and GM-CSFR gene expression was detected in 42 specimens (47%). GM-CSF expression was detected in 13 of 30 squamous cell carcinoma specimens (43%) and GM-CSFR expression was detected in 10 specimens (33%). Patients with squamous cell carcinoma coexpressing GM-CSF and GM-CSFR showed significantly poorer prognosis than those expressing neither GM-CSF nor GM-CSFR (P < 0.05, Cox-Mantel test). These results suggest that GM-CSF can have a stimulatory effect on some NSCLC.

Animals↗
PubMed1998

Simultaneous determination of urinary catecholamines and 5-hydroxyindoleamines by high-performance liquid chromatography with fluorescence detection.

A simple, selective and sensitive high-performance liquid chromatographic method with fluorescence detection is described for the simultaneous determination of catecholamines and 5-hydroxyindoleamines. The method is based on the derivatization of the amines with benzylamine in the presence of potassium hexacyanoferrate(III) under mild conditions. The resulting fluorescent derivatives are separated on a reversed-phase column, Cosmosil 5C18, using a mixture of acetonitrile and 10 mmol l-1 acetate buffer (pH 6.0) (35 + 65 v/v) as mobile phase, and are detected spectrofluorimetrically at 480 nm with excitation at 345 nm. The detection limits (signal-to-noise ratio = 3) for the amines are 2.8-236.0 fmol for an injection volume of 50 microliters. The method was successfully applied to the determination of 5-hydroxyindol-3-ylacetic acid, serotonin, norepinephrine and epinephrine in human urine. The method is simple and does not require clean-up of urine samples.

Benzylamines↗
PubMed1998

Effect of the interaction between fibronectin and VLA-4 on the proliferation of human B cells, especially a novel human B-cell line, OPM-3.

Very late antigen (VLA)-4 integrin has been suggested to play an important role in haemopoiesis. However, little is known concerning the roles of the fibronectin (FN)/VLA-4 interaction in the proliferation of human B cells. In this study we investigated the effect of immobilized FN on the proliferation of various B-cell lines, including a newly-established B-cell line, OPM-3, and human tonsillar B cells, that primarily express VLA-4 but not VLA-5. Immobilized FN significantly promoted the proliferation of OPM-3 cells and normal B cells via VLA-4. The cross-linking of beta1 integrins of OPM-3 cells resulted in the phosphorylation of the focal adhesion kinase (FAK) associated 90 kD protein, an increase in FAK-associated kinase activity, and the phosphorylation of Raf-1. Furthermore, the MEK1 inhibitor, PD98059, inhibited the FN-promoted proliferation of OPM-3 cells. These results demonstrate that the FN/VLA-4 interaction transmits the growth signal(s) which may be mediated by Ras pathway in OPM-3 cells, and suggest that OPM-3 cells may be of great value in studying the roles of the FN/VLA-4 interaction in human B-cell growth.

B-Lymphocytes↗
PubMed1998

Decreased nitric oxide-mediated natural killer cell activation in chronic fatigue syndrome.

BACKGROUND: L-Arginine (L-Arg), one of the essential amino acids, has been reported to have an immunomodulatory effect. The precise mechanism of the L-Arg-induced natural killer (NK) cell activation remains unresolved,and the effect of L-Arg on NK cells in chronic fatigue syndrome (CFS) patients has not been estimated. METHODS: NK cell function was evaluated in 20 subjects with CFS and compared with that in 21 healthy individuals. RESULTS: In healthy control subjects, NK activity was significantly increased after treatment with L-Arg, an NK function enhancer, for 24 h, whereas the same treatment failed to enhance NK activity in the CFS patients. We thus focused on L-Arg metabolism, which involves nitric oxide (NO) production through NO synthase (NOS). The expression of inducible NO synthase (iNOS) transcripts in peripheral blood mononuclear cells was not significantly different between healthy control subjects and CFS patients. The L-Arg-mediated NK cell activation was abolished by addition of NG-monomethyl-L-arginine, an inhibitor for iNOS. Furthermore, incubation with S-nitroso-N-acetyl-penicillamine, an NO donor, stimulated NK activity in healthy control subjects but not in CFS patients. CONCLUSION: These results demonstrate that the L-Arg-induced activation of NK activity is mediated by NO and that a possible dysfunction exists in the NO-mediated NK cell activation in CFS patients.

Adjuvants, Immunologic↗
PubMed1998

Maternal thyroid function in multiple pregnancy: the variable thyrotropic activity of human chorionic gonadotropin.

The present study was undertaken to evaluate thyroid function and thyrotropic action of hCG in multiple pregnancy. We examined serum samples from 9 multiple pregnant women (3 triplets and 6 twins) and 27 singleton pregnant women as control subjects. Serum hCG levels in multiple pregnancy were higher than those in singleton pregnancy in the second and third trimesters (P < 0.01). The mean free T3 and T4 concentrations in multiple pregnancy did not differ from those in singleton pregnancy in each trimester. Serum hCG levels showed a statistically significant positive correlation with free T3 and T4 levels in singleton pregnancy (P < 0.001). However, these correlations were not observed in multiple pregnancy. Thyroid stimulation activity (TSA) determined by cAMP accumulation in FRTL-5 cells in multiple pregnancy sera was significantly higher than that in singleton pregnancy in the first trimester (P < 0.05), but did not differ in the second and third trimesters. Moreover, TSA did not show any correlation with serum hCG levels in multiple pregnancy in contrast with the results in normal pregnancy. A bioactivity/immunoreactivity ratio of hCG in multiple pregnancy was lower than in singleton pregnancy in the second and third trimesters. The discrepancy between immunoreactivity and thyrotropic activity of hCG may be caused by the variable thyrotropic potency of heterogeneous hCG molecules in multiple pregnancy.

Adult↗
PubMed1998

Lower than normal expression of brain nitric oxide synthase gene in the hypothalamus of deoxycorticosterone acetate-salt hypertensive rats.

OBJECTIVE: To elucidate the role of brain nitric oxide produced by neuronal constitutive nitric oxide synthase in sodium-induced hypertension. DESIGN AND METHODS: Diets containing a high (8% NaCl), a medium (2% NaCl), and a low (0.2% NaCl) sodium content were administered to Wistar rats aged 12 weeks for 10 days or 8 weeks until they were killed. Male Wistar rats administered either deoxycorticosterone acetate, 1% NaCl or both and the respective controls were killed 2 weeks (during prehypertensive stage) or 6 weeks (during hypertensive stage) after the start of treatment. The hypothalamus and lower brainstem were excised for extraction of total RNA. Reverse transcription polymerase chain reactions of constitutive nitric oxide synthase messenger RNA and glyceraldehyde-3-phosphate dehydrogenase messenger RNA were performed, and constitutive nitric oxide synthase messenger RNA levels were expressed relative to glyceraldehyde-3-phosphate dehydrogenase messenger RNA levels. RESULTS: A high sodium intake for 10 days tended to decrease constitutive nitric oxide synthase messenger RNA levels in the hypothalamus, compared with effect of a low sodium intake. Constitutive nitric oxide synthase messenger RNA levels in the hypothalamus of deoxycorticosterone acetate-salt hypertensive rats were lower than those in the control sham-operated rats. Neither alteration of sodium intake nor administration of deoxycorticosterone with and without sodium affected constitutive nitric oxide synthase gene expression in the lower brainstem. CONCLUSIONS: Expression of neuronal constitutive nitric oxide synthase gene is downregulated in the hypothalamus of deoxycorticosterone acetate-salt hypertensive rats. This lower than normal expression of neuronal constitutive nitric oxide synthase gene in the hypothalamus could be an adaptive response to sodium-induced hypertension, and suggests that nitric oxide produced by hypothalamic constitutive nitric oxide synthase plays a role in maintenance of blood pressure in relation to sodium balance in rats.

Animals↗
PubMed1998

Amyloid beta-protein (A beta) accumulation in the putamen and mammillary body during aging and in Alzheimer disease.

Immunocytochemical studies clearly showed that amyloid beta-protein (A beta) deposits are widely distributed in the subcortical regions as well as the cortices of normal aged and Alzheimer disease (AD) brains. To investigate the temporal profile of A beta accumulation in the subcortical region, we quantitated A beta40 and A beta42 levels, using sensitive enzyme immunoassays, in the putamen and mammillary bodies of normal individuals aged 24 to 87 years and of AD patients. In these two regions, A beta42 was the predominant species; in particular, A beta42 was the only A beta species detected in the putamen. In several cases the mammillary body contained only A beta40, but not A beta42. Although the extent of A beta accumulation in the 2 subcortical regions was much less than that in the cortex of the same subject, A beta42 appears to accumulate in both subcortical regions at the same time as in the cortex and leptomeninges. In addition, the A beta42 levels in the putamen or in the mammillary body correlated with those in the occipitotemporal cortex. This strongly suggests that the extent of A beta42 accumulation in the brain is determined not only by the duration of A beta accumulation but also by other unknown regional factors. Western blotting showed that the initial A beta species to accumulate in the putamen or mammillary body varied among individuals. In some cases, an A beta42 stable dimer was the most predominant species, while in other cases a 3 or 4 kD A beta42 monomer was more abundant, suggesting that the clearance rates of the A beta42 stable dimer and monomer are different in vivo.

Adult↗
PubMed1998

Endothelin-1 inhibits pacemaker currents in rabbit SA node cells.

Our recent study demonstrated that endothelin-1 (ET-1) inhibits the pacemaker activity of sinoatrial (SA) node cells via changes in the L-type Ca2+, delayed K+, and background K+ currents. Using the whole-cell patch-clamp technique in the same preparation, we found that ET-1 reduces other pacemaker currents, the T-type Ca2+ current (ICa,T) and the hyperpolarization-activated inward current (I(f)). The inhibitory actions of ET-1 on these currents were concentration-dependent, i.e., EC50 of 0.9 nM for ICa,T and 2.3 nM for I(f), with little reversal after washout of the peptide. In the presence of BQ485, both currents were not affected by ET-1. These results indicate additional mechanisms underlying negative chronotropic actions of ET-1 on the rabbit SA node.

Animals↗