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Editorial↗
Biomedical subjects
M Nishimura
Publications and source records attributed to M Nishimura.
Eicosapentaenoic acid stimulates nitric oxide production and decreases cardiac noradrenaline in diabetic rats.
1. The aim of the present study was to investigate whether long-term oral administration of eicosapentaenoic acid increases nitric oxide (NO) production and affects cardiac sympathetic activity in rats with diabetes mellitus. 2. We measured changes in urinary excretion of NO3-, a stable NO metabolite, and cardiac noradrenaline (NA) concentrations in non-diabetic rats and streptozotocin-induced diabetic rats treated with either ethyl icosapentate (EPA-E; 100 mg/kg per day; n = 10), a purified ethyl esterification product of eicosapentaenoic acid, or vehicle (distilled water; n = 10) for 6 weeks. The effects of N(G)-nitro-L-arginine (L-NNA), a NO synthase inhibitor, on urinary NO3- excretion and cardiac NA concentrations were also investigated in diabetic rats treated with EPA-E. 3. Urinary NO3- excretion was higher at weeks 5 and 6 in diabetic rats treated with EPA-E than in diabetic rats treated with vehicle (week 5: 120+/-8 vs 51+/-11 micromol/g per day, respectively (P<0.01); week 6: 279+/-83 vs 73+/-9 micromol/g per day, respectively (P<0.01)). Cardiac NA concentrations were higher in diabetic rats than in non-diabetic rats and were decreased in the left atrium and both ventricles in diabetic rats treated with EPA-E compared with control. Systemic administration of L-NNA abolished the increase in urinary excretion of NO3- and the decrease in cardiac NA concentrations in diabetic rats treated with EPA-E. 4. Long-term oral administration of EPA-E may stimulate NO production and increased NO is likely to play a role in inhibiting enhanced cardiac sympathetic activity in diabetic rats.
Animals↗
A case of idiopathic constrictive bronchiolitis in a middle-aged male smoker.
When one sees a middle-aged male smoker who presents with progressive exertional dyspnoea and irreversible airflow obstruction, the most likely clinical diagnosis is pulmonary emphysema or chronic obstructive pulmonary disease (COPD). We report a 45-year-old male smoker who was initially suspected to have such a disease but was eventually diagnosed as having idiopathic constrictive bronchiolitis by lung biopsy, clinical history, and laboratory findings. A finding on lung computed tomography of diffuse hyperinflation but few low attenuation areas and relatively well-preserved diffusing capacity of carbon monoxide seems to be the key for suspecting this rare clinical entity. The pathological difference between this bronchiolitis and small airway disease observed in COPD will be also discussed.
Biopsy↗
Characterization of depth-related population variation in microbial communities of a coastal marine sediment using 16S rDNA-based approaches and quinone profiling.
Depth-related changes in whole-community structure were evaluated in a coastal marine sediment using a molecular fingerprinting method, terminal restriction fragment length polymorphism (T-RFLP) analysis, and a chemotaxonomic technique (quinone profiling). Dendrograms derived from both T-RFLP analysis and quinone profiling indicated a significant variation in microbial community structure between the 0-2 cm layer and deeper layers. This corresponded to the dramatic change in the redox potential, acid-volatile sulphide-sulphur and bacterial numbers observed at 0-2 cm and 2-4 cm depths. A significant change in the number of terminal restriction fragments (T-RFs) was also detected at this transition depth. However, the change in major T-RFs with depth was not seen in electropherograms. The population changes were primarily variations in minor ribotypes. Most quinone homologues were detected at all depths, although the quinone composition changed with depth. Therefore, quinone profiling also suggested that the depth-related variation was primarily attributable to minor bacterial groups rather than change in the major population structure. 16S rDNA clone library analysis revealed that clones belonging to the genera Vibrio and Serratia predominated as major bacterial groups at all depths. Our data suggested that the sediment community might result from sedimentation effects of sinking particles. Overall, our results demonstrated that the combined methods of T-RFLP analysis and quinone profiling were effective for assessing depth-related microbial populations.
DNA, Ribosomal↗
The role of computed tomographic scanning in diagnosing mediastinal node involvement in non-small cell lung cancer.
OBJECTIVES: The reliability of computed tomographic scanning in evaluating mediastinal node involvement is controversial because of the high false result rate. We attempted to identify significant factors responsible for false-positive and false-negative scans. METHODS: From August 1992 through April 1997, 401 patients with lung cancer who underwent major lung resection and systematic lymph node dissection were enrolled in this study. We retrospectively examined mediastinal node size, tumor location, maximum tumor dimension, the presence or absence of obstructive pneumonia, atelectasis, pulmonary fibrosis, and lymph node calcification on contrast-enhanced computed tomographic scans. We identified clinical and radiologic factors responsible for the false results by using univariate and multivariable analysis. RESULTS: Central tumor location proved to be a significant factor of false-positive scans. Elevated carcinoembryonic antigen level and larger tumor dimension were significant factors of false-negative scans. In patients with a peripheral tumor smaller than 40 mm and normal levels of serum carcinoembryonic antigen, sensitivity, specificity, positive predictive value, and negative predictive value were 6%, 93%, 8%, and 90%, respectively. The reliability of computed tomographic scanning in this low-risk subgroup was high in detecting N0-1 disease but low in diagnosing N2 disease. CONCLUSION: It is not possible to accurately diagnose N2 disease by using lymph node size on computed tomographic scanning alone, especially in patients with a central tumor, an elevated serum carcinoembryonic antigen level, or a tumor of 40 mm or larger. A preoperative invasive staging procedure is indicated in these populations and may not be indicated in the population with normal computed tomographic scan results without any of these risk factors.
Aged↗
P-selectin participates in cardiopulmonary bypass-induced inflammatory response in association with nitric oxide and peroxynitrite production.
OBJECTIVES: P-selectin participates in the development of inflammatory disorders. Cardiopulmonary bypass is thought to induce inflammatory response and increase nitric oxide production. To evaluate the role of P-selectin in bypass-induced inflammatory response and its association with nitric oxide production, we examined the effect of P-selectin monoclonal antibody in a rat model of cardiopulmonary bypass. METHODS: Twenty adult Sprague-Dawley rats undergoing cardiopulmonary bypass for 60 minutes were divided into 2 groups. A 3-mg/kg dose of anti-rat specific P-selectin monoclonal antibody (ARP2-4; Sumitomo Pharmaceuticals, Osaka, Japan) was administered into the priming solution before bypass in group P (n = 10) and a 3-mg/kg dose of PNB1.6 (nonblocking monoclonal antibody) was added in group C for control (n = 10). RESULTS: At the termination of bypass and 3 hours after the termination of bypass, plasma levels of interleukins 6 and 8, nitrate/nitrite, the percentage ratio of nitrotyrosine to tyrosine (an indicator of peroxynitrite formation), and the respiratory index were significantly higher than before bypass in both groups, and they were significantly lower in group P than in group C. Plasma P-selectin level in group C and exhaled nitric oxide concentration in both groups at termination of bypass were significantly lower than those before bypass, and they were significantly higher 3 hours after termination of bypass than before bypass in both groups. Plasma P-selectin level and exhaled nitric oxide concentration in group P were significantly higher than those in group C at the end of bypass, but they were significantly lower 3 hours after the termination of bypass. CONCLUSIONS: These results demonstrate that P-selectin may participate in the augmentation of bypass-induced inflammatory response in association with nitric oxide and peroxynitrite production.
Animals↗
Biotransformation of the xanthine oxidase inhibitor BOF-4272 and its metabolites in the liver and by the intestinal flora in rat.
1. BOF-4272, (+/-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one), is a new drug intended for the treatment of hyperuricaemia. 2. This paper describes the detailed biotransformation of BOF-4272 and its metabolites in the liver and by the intestinal flora in rat. 3. Only the sulphoxide metabolite (M6) was detected in plasma in small amounts after the intravenous administration of M4 (hydroxy-BOF-4272) and in culture medium after the addition of M4. 4. Only M3 (the sulphide metabolite of M4) was detected in faeces, and its amount was approximately 50% of the administered dose within 1 day after the intravenous administration of M4. 5. These findings suggest that M4, which is excreted in the bile, is metabolized mainly to M3 (the corresponding sulphide of M4) by the intestinal flora in rat, whereas little M4 is metabolized to the sulphoxide (M6) in the rat liver. 6. M2, which is the demethylated form of BOF-4269, was detected in faeces after the oral administration of BOF-4272 to rat in which the common bile duct was cannulated, suggesting that BOF-4272 is metabolized to BOF-4269 and then to M2 by the intestinal flora. 7. These findings suggest that in rat the sulphoxide of BOF-4272 and its metabolites are demethylated and reduced by the intestinal flora, with other types of biotransformation occurring in the liver.
Animals↗
Polygenic resistance to mouse pulmonary adenomas.
Susceptibility to urethan-induced pulmonary adenomas (PA) in mice is under polygenic control. To analyze these traits in detail, we generated a set of recombinant inbred (RI) mouse strains, called SMXA, from an intercross between PA-susceptible A/J and resistant SM/J, and established a strain distribution pattern (SDP) table of 158 marker loci for SMXA RI strains. From the SDP table, it was possible to estimate the allele for 4 known PA susceptibility (Pas) loci in all members of SMXA RI strains. We compared combinations of Pas loci alleles with the data of number of PA induced by urethan. One of the RI strains, SMXA24, showed extremely low PA numbers, whereas they had the A/J-derived alleles at all 4 Pas loci. F1 hybrids of SMXA24 and A/J developed as few PA as SMXA24 on exposure to urethan. To confirm the hypothesis that SMXA24 has dominant PA resistance gene(s), we examined a backcross generation to A/J for multiplicity of PA. A preliminary genome scan followed by quantitative trait locus analysis revealed two resistance loci, one on mouse chromosome 11 (MMU11) (logarithm of odds [LOD] score 4.35) and another on MMU12 (LOD score 6.47). They were named Par1 and Par3, respectively. Both loci were epistatic to Pas1, the major susceptibility loci on MMU6. We next asked if such dominant resistance loci play some role in human lung cancer by studying possible loss of heterozygosity (LOH) at syntenic chromosomal segments in 79 human lung cancers, including 30 adenocarcinomas, 25 squamous cell carcinomas (SQ), and 24 small cell carcinomas (SCC). The map positions of Par1 and Par3 correspond to human 17q11-23 and 14q11-24. Of 30 adenocarcinomas, LOH was found in 53% at 17q and in 30% at 14q. For both SQ and SCC, LOH in 17q were about 10%, but LOH in 14q was about 30% to 42%. Therefore, a gene in 17q seemed to be selective for adenocarcinomas, probably at the level of the target cell. In contrast, another gene in 14q affected all 3 types of lung carcinomas, suggesting it is related to the progression of lung tumors in general. A comparative approach may provide useful information for understanding human cancers.
Adenocarcinoma↗
Kasabach-Merritt syndrome in a Jehovah's Witness infant.
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Antineoplastic Agents, Hormonal↗
Secretion of hCG/beta-hCG by squamous cell carcinoma of the lung in a 31-year-old female smoker.
We describe a rare case of pulmonary squamous cell carcinoma secreting human chorionic gonadotropin (hCG) and its beta-subunit (beta-hCG) in a young female smoker. A 31-year-old mother of one child had been suffering from dysfunctional uterine bleeding for about 1 year. Pelvic examinations and abdominal ultrasonography yielded no abnormal findings and no signs of pregnancy. She developed a pain in the right chest and a huge (12x10 cm) squamous cell carcinoma was diagnosed in the right lower lobe. The serum hCG and beta-hCG levels were high: hCG 5611 mlU/ml (normal upper limit 0.7 mIU/ml), beta-hCG 12 238 mIU/ml (normal upper limit 0.5 mIU/ml). The patient underwent right lower lobectomy and systematic lymph node dissection. Microscopic study showed a poorly differentiated squamous cell carcinoma. The pathological stage was T2N0M0, stage IB. Immunohistochemical staining of the tumor was strongly positive for hCG. The serum hCG level returned to normal 1 month after the operation, while an additional 2 months were necessary for the beta-hCG level to normalize. Dysfunctional uterine bleeding disappeared and the patient is doing well, with no signs of recurrence, 9 months after the resection.
Adult↗
Lung cancer implantation in the chest wall following percutaneous fine needle aspiration biopsy.
We describe a 70-year-old man with lung cancer implantation in the chest wall following percutaneous fine needle aspiration biopsy. He underwent lobectomy after percutaneous transthoracic fine needle aspiration biopsy using a 19-gauge needle. Twenty-six months after the biopsy, he noticed a hard subcutaneous tumor at the biopsy site in the chest wall. Ribs and intercostal muscles were resected. The primary lung tumor and the chest wall tumor were histologically identical, but were not contiguous to each other. We concluded that the subcutaneous tumor was due to needle biopsy implantation. This complication is extremely rare, but open biopsy should always be considered as a possible alternative. During the procedure, care must be taken with the least chance of implantation and patients should be observed carefully after needle biopsy.
Adenocarcinoma↗
Histochemistry of food tissue by colour scanning electron microscopy.
A low-vacuum scanning electron microscope (SEM) allows microscopy of insulating specimens without metal coating, and so preserves the intact colour information on the specimen surface. We have attempted a new approach to characterize constituent distribution of food tissues by a histochemical method utilizing a colour SEM with an optical microscope and the low-vacuum SEM through digital image processing. To observe food tissues such as brown rice and adzuki bean, a colour SEM image of the specimen that has been stained by a modified method used in optical microscope histochemistry has proved to provide information of both the microscopic structure and constituent distribution on the specimen surface.
Fabaceae↗
Tissue and intracellular localization of indican and the purification and characterization of indican synthase from indigo plants.
Indican (indoxyl beta-D-glucoside) was found to accumulate only in green leaves of the indigo plant, and not in any other tissues. Comparisons of the indican content of protoplasts and vacuoles showed that indican was stored only in the vacuole of the cell. Indican content appeared and increased with the appearance and growth of leaves. In mature plants, the younger leaves contained larger amounts of indican than the older ones. Cell extracts of young leaves of indigo plant catalyzed the synthesis of indican from UDP-glucose and indoxyl. Indican synthase was extracted and purified from young leaves. The enzyme was separated into two fractions by anion-exchange chromatography. The enzyme in the fraction which was eluted by 0.1 M NaCl had a molecular weight of 53,000 by SDS-PAGE. Optimum pH of the enzyme was at about 10.0, indicating that the enzyme is likely localized in a different intracellular compartment from that of indican storage. The enzyme showed normal Michaelis-Menten kinetics and a K(m) value of 0.13 mM for UDP-glucose.
Glucosyltransferases↗
Characterization of organelles in the vacuolar-sorting pathway by visualization with GFP in tobacco BY-2 cells.
We have shown the localization and mobilization of modified green fluorescent proteins (GFPs) with various signals in different compartments in a vacuolar-sorting system of tobacco BY-2 cells. In contrast to the efficient secretion of GFP from the transformed cells expressing SP-GFP composed of a signal peptide and GFP, accumulation of GFP in the vacuoles was observed in the cells expressing SP-GFP fused with the C-terminal peptide of pumpkin 2S albumin. This indicated that this peptide is sufficient for vacuolar targeting. Interestingly, the fluorescence in the vacuoles disappeared sharply at 7 d after inoculation of the cells, but it appeared again after re-inoculation into a new culture medium. When SP-GFP was fused with the region, termed PV72C, including a transmembrane domain and a cytosolic tail of a vacuolar-sorting receptor PV72, GFP-PV72C was detected in the Golgi-complex-like small particles. Prolonged culture showed that GFP-PV72C that reached the prevacuolar compartments was cleaved off the PV72C region to produce GFP, that arrived at the vacuoles to be diffused. These findings suggested that the vacuolar-sorting receptor might be recycled between the Golgi complex and prevacuolar compartments.
Base Sequence↗
Reduction to below threshold levels of glycolate oxidase activities in transgenic tobacco enhances photoinhibition during irradiation.
The effects of decreased flux in the glycolate pathway on photoinhibition was investigated in transgenic tobacco (Nicotiana tabacum L. cv. SR1) plants. These plants harbored a pumpkin cDNA for glycolate oxidase (GO), an enzyme in the glycolate pathway, under the control of the cauliflower mosaic virus 35S promoter. Some transformants showed both reduced amounts and reduced activities of GO. The decrease of GO was enhanced at a later growth stage of these transformants, whereas no changes were observed in the amounts of other enzymes in the glycolate pathway, such as hydroxypyruvate reductase and serine glyoxylate aminotransferase. The phenotype grown under a low light condition (30 microE s(-1) m(-2)) resembled that of the wild type. Transformants with about 35% lower GO activity than wild type, had a lower Fv/Fm under 500 microE s(-1) m(-2) irradiation for 8 h. After 60 microE s(-1) m(-2) irradiation for 8 h, Fv/Fm was lowered in some transformants with less than 20% of the GO activity of the wild type. These results suggest that photosynthesis was susceptible to photoinhibition with reduction to below threshold levels of GO activities and that higher activities of GO are required under a higher irradiation. The increase in the electron transport rate (ETR) with increased irradiation was suppressed only in transformants that had GO activity one-third less than the wild type, suggesting that the regeneration of the substrate for the Calvin cycle was decreased only when there was an extreme reduction of GO. These results also suggest that the photosystem was disturbed when the concentration of the substrate for the Calvin cycle decreased until it became insufficient to receive the excess photon energy generated in each light environment.
Alcohol Oxidoreductases↗
Insertion of the LINE retrotransposon MGL causes a conidiophore pattern mutation in Magnaporthe grisea.
We obtained three Magnaporthe grisea morphological mutants that had the LINE transposon MGL inserted into the ACR1 locus. Sequence analysis revealed that ACR1 is homologous to medA, a developmental regulator of Aspergillus nidulans conidiation. These results demonstrated that MGL elements could transpose and cause insertional mutagenesis in M. grisea.
Amino Acid Sequence↗
Effect of patient-triggered ventilation on respiratory workload in infants after cardiac surgery.
BACKGROUND: Patient-triggered ventilation (PTV) is commonly used in adults to avoid dyssynchrony between patient and ventilator. However, few investigations have examined the effects of PTV in infants. Our objective was to determine if pressure-control PTV reduces infants' respiratory workloads in proportion to the level of pressure control. We also explored which level of pressure control provided respiratory workloads similar to those after the extubation of the trachea. METHODS: When seven post-cardiac surgery infants, aged 1 to 11 months, were to be weaned with the pressure-control PTV, we randomly applied five levels of pressure control: 0, 4, 8, 12, and 16 cm H2O. All patients were ventilated with assist-control mode, triggering sensitivity of 1 l/min, and positive end-expiratory pressure of 3 cm H2O. After establishing steady state conditions at each level of pressure control, arterial blood gases were analyzed and esophageal pressure (Pes), airway pressure, and airflow were measured. Inspiratory work of breathing (WOB) was calculated using a Campbell diagram. A modified pressure-time product (PTPmod) and the negative deflection of Pes were calculated from the Pes tracing below the baseline. The measurement was repeated after extubation. RESULTS: Pressure-control PTV supported every spontaneous breath. By decreasing the level of pressure control, respiratory rate increased, tidal volume decreased, and as a result, minute ventilation and arterial carbon dioxide partial pressure were maintained stable. The WOB, PTPmod, and negative deflection of Pes increased as pressure control level was decreased. The WOB and PTPmod at 4 cm H2O pressure control and 0 cm H2O pressure control and after extubation were significantly greater than those at the pressure control of 16, 12, and 8 cm H2O (P < 0.05). The WOB and PTPmod were almost equivalent after extubation and at 4 cm H2O pressure control. CONCLUSIONS: Work of breathing and PTPmod were changed according to the pressure control level in post-cardiac surgery infants. PTV may be feasible in infants as well as in adults.
Cardiac Surgical Procedures↗
Autotriggering caused by cardiogenic oscillation during flow-triggered mechanical ventilation.
OBJECTIVES: We noticed that in some patients after cardiac surgery, when flow triggering was used, cardiogenic oscillation might be autotriggering the ventilatory support. In a prospective study, we evaluated the degree of cardiogenic oscillation and the frequency rate of autotriggering. We suspected that autotriggering caused by cardiogenic oscillation was more common than clinically appreciated. DESIGN: Prospective, nonrandomized, clinical study. SETTING: Surgical intensive care unit in a national heart institute. PATIENTS: A total of 104 adult patients were enrolled after cardiac surgery. INTERVENTIONS: During the study period, patients were paralyzed and ventilated with intermittent mandatory ventilation at a rate of 10 breaths/min, pressure support of 10 cm H2O, and flow triggering with a sensitivity of 1 L/min. MEASUREMENTS AND MAIN RESULTS: Because the patients would not be able to breathe spontaneously, we counted pressure-support (PS) breaths as instances of autotriggering. Then, we classified the patients into two groups according to the number of PS breaths: an "AT group" (PS breaths of >5/min) and a "non-AT group" (PS breaths of < or =5/min). If autotriggering occurred, we decreased the sensitivity so autotriggering disappeared (threshold triggering sensitivity). The intensity of cardiogenic oscillation was assessed as the flow and airway pressure at the airway opening. A total of 23 patients (22%) demonstrated more than five autotriggered breaths/min. During mechanical ventilation, the inspiratory flow fluctuation caused by cardiogenic oscillation was significantly greater in the AT group than in the non-AT group (4.67+/-1.26 L/min vs. 2.03+/-0.86 L/min; p<.01). The AT group also showed larger cardiac output, higher ventricular filling pressures, larger heart size, and lower respiratory system resistance than the non-AT group. As the inspiratory flow fluctuation caused by cardiogenic oscillation increased, the level of triggering sensitivity also was increased to avoid autotriggering. In the AT group with 1 L/min of sensitivity, the respiratory rate increased (19.9+/-2.7 vs. 10+/-0 breaths/min, p<.01), Paco2 decreased (30.8+/-4.0 torr [4.11+/-0.36 kPa] vs. 37.6+/-4.3 torr [5.01+/-0.57 kPa]; p < .01), and mean esophageal pressure increased (7.7+/-3.0 vs. 6.9+/-3.0 cm H2O; p<.01) compared with the threshold triggering sensitivity. CONCLUSIONS: Autotriggering caused by cardiogenic oscillation is common in postcardiac surgery patients when flow triggering is used. Autotriggering occurred more often in patients with more dynamic circulation. Autotriggering caused respiratory alkalosis and hyperinflation of the lungs.
Adult↗