Biomedical subjects
Publications and source records attributed to N Yagi.
We demonstrated dynamical observation of an individual nanocrystal in supercooled liquid water with the guidance of x-ray diffracted spots from the nanocrystal itself. This new system, which we call diffracted x-ray tracking, monitored small Brownian motions (D=0.68 mrad(2)/s at 233 K) of a single nanoparticle in real time and real space.
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The effect of fibrin glue on inhibition of pericardial adhesions was tested using 26 beagle dogs. Dacron patches were sutured to the heart and tincture of iodine was applied to promote adhesions. Fibrin glue (3 ml) was sprayed over the patches in 15 dogs (test group), and was not separated in the remaining 11 dogs (control group). All animals in the test group had minimal adhesions between the pericardium and the epicardium or patched region, and an accumulation of gelatinous material was found in the subpericardial space. Marked fibrosis and a poor demarcation of the subpericardial space were found in the control group. The adhesion score and the visibility of coronary anatomy in the test group were significantly better than in the control group. The tension strength in the test group was significantly less than in the control group. We concluded, therefore, that fibrin glue may also be useful as an adhesion inhibitor.
Introduction of liposomes into target cells is important for drug delivery systems. For this purpose, the surface of the liposome is equipped with ligand peptides, which may bind to specific receptors on the cell membrane. An artificial novel lipopeptide (MSH-C4A2) containing the alpha-melanocyte-stimulating hormone (alpha-MSH) sequence and two long alkyl chains was designed and synthesized, and the liposome, composed of egg phosphatidylcholine (EPC) and MSH-C4A2, was prepared. The stability of the liposome was estimated by measuring calcein leakage from the liposome inner phase. The stability of the liposome decreased upon addition of MSH-A4C2, which seemed to be attributable to the amphiphilic property of the peptide moiety (alpha-MSH) of MSH-A2C4. The stability was, however, recovered fairly well upon addition of cholesterol (Ch) or phosphatidylglycerol (PG). It was concluded therefore that the ternary system, MSH-C4A2/Ch/EPC or MSH-C4A2/PG/EPC, is suitable for preparing the functional liposome.
OBJECTIVE: The aim of this study is to compare the pulmonary function after a segmentectomy with that after a lobectomy for small peripheral carcinoma of the lung. PATIENTS AND METHODS: Between 1993 and 1996, segmentectomy and lobectomy were performed on 48 and 133 good-risk patients, respectively. Lymph node metastases were detected after the operation in 6 and 24 patients of the segmentectomy and lobectomy groups, respectively. For bias reduction in comparison with a nonrandomized control group, we paired 40 segmentectomy patients with 40 lobectomy patients using nearest available matching method on the estimated propensity score. RESULTS: Twelve months after the operation, the segmentectomy and lobectomy groups had forced vital capacities of 2.67 +/- 0.73 L (mean +/- standard deviation) and 2.57 +/- 0.59 L, which were calculated to be 94.9% +/- 10.6% and 91.0% +/- 13.2% of the preoperative values (P =.14), respectively. The segmentectomy and lobectomy groups had postoperative 1-second forced expiratory volumes of 1.99 +/- 0.63 L and 1.95 +/- 0.49 L, which were calculated to be 93.3% +/- 10.3% and 87.3% +/- 14.0% of the preoperative values, respectively (P =.03). The multiple linear regression analysis showed that the alternative of segmentectomy or lobectomy was not a determinant for postoperative forced vital capacity but did affect postoperative 1-second forced expiratory volume. CONCLUSION: Pulmonary function after a segmentectomy for a good-risk patient is slightly better than that after a lobectomy. However, segmentectomy should be still the surgical procedure for only poor-risk patients because of the difficulty in excluding patients with metastatic lymph nodes from the candidates for the procedure.
BACKGROUND: Neutrophil infiltration and lipid peroxide accumulation are involved in reperfusion-induced gastric mucosal injury in nitric oxide-depleted rats. AIM: To assess the effect of vitamin E on this injury. METHODS: After ischaemia-reperfusion, the total area of erosions, lipid peroxide contents in gastric mucosa, and gastric neutrophil accumulation were compared between nitric oxide-depleted rats with deficient, normal, and increased vitamin E intake over 8 weeks. Thiobarbituric acid-reactive substances and tissue-associated myeloperoxidase activity were measured in gastric mucosa as indices of lipid peroxidation and neutrophil infiltration. RESULTS: The total area of erosions was significantly increased in the vitamin E-deficient group compared with the sufficient-intake and vitamin-supplemented groups. Both thiobarbituric acid-reactive substances and myeloperoxidase activity also were significantly increased in the vitamin E-deficient group compared with others. The total area of erosions closely paralleled the increases in both thiobarbituric acid-reactive substances and myeloperoxidase activity. CONCLUSION: These results indicate that the inhibition of lipid peroxidation and interference with neutrophil infiltration by vitamin E may be responsible for its cytoprotective effect in ischaemia-reperfusion.
We report a case of complete unilateral anomalous connection of the left pulmonary veins to the coronary sinus with unroofed coronary sinus syndrome. Magnetic resonance imaging (MRI) was a useful diagnostic method in our case. At operation, a cut was made from the orifice of the coronary sinus to the unroofed portion of the coronary sinus, and part of the lower atrial septum was excised. The resulting defect was closed with a Dacron patch, diverting the left pulmonary venous blood into the left atrium.
A 71-year-old woman, who presented tracheobronchial obstruction caused by a thoracic aortic aneurysm, was admitted to our institution. Although she had multiple cerebral infarctions, old myocardial infarction, bilateral iliofemoral atherosclerotic lesions with abdominal aortic aneurysm, and superior vena cava syndrome, aneurysmectomy was undertaken in order to rescue her from respiratory insufficiency. The operation successfully relieved her of exertional dyspnea and dysphagia.
The low divergent x-ray beam from the third-generation synchrotron radiation source such as SPring-8 enables us to observe refraction of x rays that is in the range of microradians. Under an experimental condition for which ray optics is a good approximation, we found that the refraction produces a high-contrast projection image of a mouse when it was recorded at 6.5 m behind the specimen. Especially, the lung is visualized far better than with the conventional imaging which utilizes absorption of x rays. This is a promising new technique for the diagnosis of diseases in the human lung with a low radiation dose.
Retarded capsules containing 1 mg bumetanide (BN) were prepared and their in vivo absorption and diuretic effect after oral administration in human subjects were studied. For comparison, commercially available tablets of BN (rapid effect) were administered orally. The mean value of the area under the plasma concentration time curve (AUC) after administration of retarded capsules was about one half that of the tablets. The mean maximum plasma concentration (Cmax) and the mean maximum urinary excretion rate of BN after administration of retarded capsules were also about one half compared to those of the tablets. Cumulative urinary volumes for 24 h, however, were not significantly different between retarded capsules and tablets. Peak times for the urinary excretion rate of BN, urine flow rate and the Cmax after administration of retarded capsules were significantly delayed compared to those of tablets. Clockwise hysteresis relationships between the urine flow rate and plasma concentration or urinary excretion rate of BN were observed after administration of retarded capsules. From these studies, retarded capsules of BN possessed a mild diuresis and its diuretic effect was maintained for a few hours after administration.
To investigate the relationships between the activity in potential operated Ca2+ channels (POC), blood pressure, and endothelium in hypertension, we tested the contractile responses to a Ca2+ channel agonist Bay K 8644 (BAY K) in aorta from deoxycorticosterone-acetate-saline (DOCA-S) and reduced renal mass-saline (RRM-S) hypertensive rats. The effects of mechanical rubbing, N omega-Nitro-L-Arginine Methyl Ester (l-NAME) and indomethacin were also examined. Sensitivity to BAY K increased in experimental rats before they became hypertensive and contractile responses were enhanced as hypertension developed. Force development to BAY K was correlated with blood pressure levels. Endothelium removal enhanced the contractile response to BAY K. L-NAME, but not indomethacin, potentiated the response to BAY K. Contractile response to BAY K was negatively correlated with relaxation to acetylcholine. An enhanced contractile response to BAY K was observed also in aged rats. Enhanced activation of vascular POC in hypertension results from elevated blood pressure and partly from diminished inhibitory action of endothelium. Senescence also enhances vascular POC activity.
We report two cases of aorto-gastrointestinal fistula. Case 1, a 60-year-old man, suffered from repeat hematemesis. He was preoperatively diagnosed as aortoesophageal fistula with thoracic aortic aneurysm and was successfully treated by graft replacement of the aneurysm. Case 2, a 73-year-old man, presented with massive gastrointestinal bleeding, yet repeat endoscopical examination did not reveal the origin of the bleeding. He died of catastrophic hematochezia. The pathological findings at autopsy revealed an aortoduodenal fistula. These two cases suggested the importance to consider an aorto-gastrointestinal fistula in the differential diagnosis of patients presenting gastrointestinal hemorrhage.
Overexpression of urokinase plasminogen activator (uPA) has been proposed to be one of the mechanisms by which malignant glioma cells cause pericellular proteolysis of stromal structures during brain-tissue invasion. However, knowledge about the mechanisms that regulate uPA in glioma cells is still rather scant. Growth factors, particularly epidermal growth factor and basic fibroblast growth factor (bFGF), regulate uPA synthesis in various nonglial cells. Because these factors have been associated with glioma invasion, we thought that perhaps similar events may occur in glioma cells. In this study, we demonstrate that growth factors regulate uPA gene transcription in glioma cells by induction of Ets-1 transcription factor. Serum and bFGF treatment concomitantly stimulated baseline levels of Ets-1 and uPA mRNA and protein, and this was associated with a marked increase in the migration and invasion potentials of glioma cells in vitro. Treatment of cells with antisense Ets-1 but not the control sense oligonucleotides concurrently inhibited the expression of Ets-1 and uPA, and this blocked glioma cell migration and invasion by more than 50%. In addition, medium conditioned by antisense Ets-1 oligonucleotide-treated cells showed markedly reduced uPA activity, as determined by casein zymography. These results strongly suggest that serum and bFGF control glioma invasion by inducing synthesis of Ets-1 transcription factor, which directly up-regulates expression of uPA in glioma cells. Antisense inhibition of Ets-1 expression may therefore provide a potential and exciting therapeutic target for preventing invasion by glioma cells.
High Energy Accelerator Research Organization (KEK), Tsukuba, Japan.High-resolution X-ray diffraction studies on striated muscle fibres were performed using a hard X-ray undulator installed in the Tristan main ring at KEK, Tsukuba, Japan. The performance of the undulator, along with an example experiment which exploited the unique characteristics of undulator radiation, are reported. The vertical divergence angle of the first harmonic of the undulator was approximately 10 micro rad under 8 GeV multi-bunch operating conditions and the peak photon flux density was estimated to be approximately 3 x 10(16) photons s(-1) mrad(-2) (0.1% bandwidth)(-1) (10 mA)(-1). The well collimated X-ray beam from the undulator made it possible to resolve clearly, with high angular resolution ( approximately 700 nm), the closely spaced diffraction peaks on the meridional axis in the X-ray patterns arising from the thick filaments of a striated muscle under static conditions. By fitting the meridional intensity pattern, a model for the molecular arrangement of the constituent proteins in the thick filaments is proposed. These studies of muscle demonstrate the promise of undulator radiation from third-generation sources for high-resolution diffraction studies.
The role of the magnocellular reticular formation (MGRF) of the brainstem on learning and memory was examined in memory-deficient mice with spontaneous spongy degeneration in the brainstem (senescence-accelerated mouse, SAMP8) and control mice (accelerated-senescence resistant mouse, SAMR 1). SAMP8 showed spontaneous age-related impairment of learning and memory, as determined by passive and active avoidance responses. The deficits of learning and memory function in passive avoidance performances began at two months of age and increased with ageing. In the brains of SAMP8 at one month of age and older, spongy degeneration was mainly observed in the brainstem, while no vacuoles were evident in SAMR1 control (normal ageing mouse) brains in the age range tested (up to 12 months). The vacuolization in SAMP8 was marked in the MGRF, especially in the dorsomedial MGRF. Quantitative analysis of the vacuolization showed that the total area and number of vacuoles in the MGRF increased with age, and they were affected by the degree of deficits in learning and memory. The latency 24 h after footshock in passive avoidance tests decreased with the increase in total area and number of vacuoles in MGRF. The number of shocks in active avoidance tests increased with the increase in total number and area of vacuoles. Thus, learning and memory ability in passive and active avoidance responses deteriorated with enlargement in the vacuolated area in MGRF, and it was assumed that MGRF (especially, the dorsomedial part) possesses functions related to learning and memory. To confirm this notion, behavior and memory tests (passive avoidance and active avoidance tests, open field tests and shock sensitivity measurements) were carried out in SAMR1 mice, whose bilateral dorsomedial MGRF was destroyed electrolytically (MGRF-lesioned mice). The MGRF-lesioned mice showed no difference from sham mice in sensory threshold or open field activity; however, there was severe deterioration in passive avoidance behavior and impairment in the active avoidance performances. From the results in SAMP8 and MGRF-lesioned mice, it was confirmed that MGRF (especially the dorsomedial part) has functions related to learning and memory, and is one part in the learning and memory system of the brain. Thus, SAMP8 can serve as a model of RF-lesioned mice with impaired learning and memory functions.
The Cdk inhibitor p21/WAF1 can be transcriptionally activated by wild-type p53, not by mutant p53, and functions to block cell-cycle progression in many human neoplasms. We examined the immunohistochemical expression of p53 and p21 in 35 human primary glioblastomas in relation to tumor proliferation potential as assessed by the Ki-67 labeling index (LI) and the glioblastoma apoptosis index (AI). The expression of mutant p53 was observed in 74% of glioblastomas, wild-type p53 in 18% of glioblastomas, and p21 in 57% of glioblastomas. p21 expression was seen in 15 of 26 mutant p53-positive and 2 of 4 wild p53-positive tumors. Tumor Ki-67 LI correlated neither with p53 nor with p21 expression in glioblastomas. Apoptosis was identified in all 15 glioblastomas examined, with a mean (+/-SD) Al of 1.69+/-1.54, and correlated neither with p53 (wild or mutant) nor with p21 expression. The results of the present study suggest that p53 mutation and p21 protein expression are frequent in primary glioblastoma but lack correlation with tumor proliferation potential and apoptosis. The lack of correlation between p21 and p53 also suggests that p21 in glioblastomas may be induced by a p53-independent pathway.
Hypothermia is reported to increase intensive care unit (ICU) mortality. The heat loss that occurs during continuous renal replacement therapy (CRRT) favors the development of hypothermia. In an effort to assess the influence of CRRT on body temperature, we reviewed the records of 72 consecutive ICU patients treated with CRRT and further prospectively studied the temperature in the inlet and outlet lines for blood and dialysate of 27 other patients at various flow settings during continuous venovenous hemodialysis (CVVHD). Among the 72 retrospective cases, 36 episodes of hypothermia (core body temperature <35.5 degrees C) occurred and persisted for a mean of 2.6+/-1.8 days. It was more frequent during venovenous than arteriovenous modalities (31 of 67 v5 of 20, respectively); no patients developed hypothermia during arteriovenous slow continuous ultrafiltration (AVSCUS), whereas 48% of the patients undergoing CVVHD became hypothermic, occurring earlier in the therapy course (days 2 to 4). Mean arterial pressure (MAP) tended to increase after CRRT initiation, but absolute changes were not statistically significant. In the prospective arm, the CVVHD circuit temperatures were directly measured. Whereas no attempt was made to change body temperature, stepwise changes in blood (Qb) and dialysate flow rate (Qd) produced venous circuit temperature changes: the higher the Qb, the smaller the arteriovenous temperature differences independent of changes in Qd (P < 0.001). Also, venous circuit temperature varied directly with Qd at fixed Qb (P < 0.001). This relationship also held for temperature conversion to lost energy units per minute. Using room temperature dialysate, CRRT may significantly lower patients' core temperatures. Although the clinical significance of this effect is not clear at this point, energy loss during CVVHD may be important in hemodynamic stability or patient prognosis.
Nitric oxide (NO) modulation of ischemia-reperfusion injury was investigated by measuring lipid peroxide and neutrophil accumulation in rat stomachs treated with NG-nitro-L-arginine (L-NNA), a specific NO synthase inhibitor. Ischemia-reperfusion injury was induced in the rat stomach. Treatment with L-NNA for 3 days at a dose of 3 mg/kg/day significantly enhanced this injury. This enhancement was reversed by the simultaneous administration of L-arginine at a dose of 30 mg/kg/day. Both thiobarbituric acid (TBA)-reactive substances, an index of lipid peroxidation, and myeloperoxidase (MPO) activity, an index of tissue-associated neutrophil accumulation, were increased in the gastric mucosa after ischemia-reperfusion. L-NNA treatment enhanced these increases in TBA-reactive substances and MPO activity. The increase in the area of gastric erosions correlated closely with accumulation of TBA-reactive substances as well as the increase in MPO activity. Enhancement of ischemia-reperfusion injury by L-NNA treatment was inhibited by injection with anti-neutrophil antibody, anti-platelet activating factor (PAF) antagonist, and anti-leukotriene B4 (LTB4) receptor antagonist. In addition, the increase in TBA-reactive substances and MPO activity was decreased by these antibodies or antagonists. Enhancement of reperfusion-induced gastric mucosal injury associated with inhibition of NO synthesis may involve neutrophil infiltration and lipid peroxide accumulation in the gastric mucosa, mediated by PAF and LTB4.