Three-dimensional characterization of ODS ferritic steel using by FIB-SEM serial sectioning method.

Considerable attention has been paid to the research of the electron tomography due to determine the three-dimensional (3D) structure of materials [1]. One of the electron tomography techniques, focused ion beam/scanning electron microscopy (FIB-SEM) imaging has advantages of high resolutions (10 nm), large area observation (µm order) and simultaneous energy dispersive x- ray microanalysis (EDS)/ electron backscatter diffraction (EBSD) analysis. The purpose of this study, three-dimensional EBSD analysis of ODS ferritic steel which carried out cold work using FIB-SEM equipment was conducted, and it aimed at analyzing the microstructure obtained there. The zone annealing tests were conducted for ferritic steel [2,3], which were produced through mechanical alloying and hot-extrusion. After zone annealing, specimens were mechanically polished with #400∼4000 emery paper, 1 µm diamond paste and alumina colloidal silica. The serial sectioning and the 3D-electron backscattering diffraction (3D-EBSD) analysis were carried out. We made the micro pillar (30 x 30 x 15 µm). The EBSD measurements were carried out in each layer after serial sectioning at a step size and milling depth was 80 nm with 30 slices. After EBSD analysis, the series of cross-sectional images were aligned according to arbitrarily specified areas and then stacked up to form a volume. Consequently, we obtained the 3D-IPF maps for ODS ferritic steel. In this specimen, the {111} and {001} grains are layered by turns. In addition, the volume fraction value of both plane are similar. The aspect ratio increases with specimen depth. The 3D-EBSD mapping is useful to analysis of the bulk material since this method obtain many microstructure information, such a shape, volume and orientation of the crystal, grain boundary.

Effects of green tea extract and (-)-epigallocatechin-3-gallate on pharmacokinetics of nadolol in rats.

Green tea catechins have been shown to affect the activities of drug transporters in vitro, including P-glycoprotein and organic anion transporting polypeptides. However, it remains unclear whether catechins influence the in vivo disposition of substrate drugs for these transporters. In the present study, we investigated effects of green tea extract (GTE) and (-)-epigallocatechin-3-gallate (EGCG) on pharmacokinetics of a non-selective hydrophilic ß-blocker nadolol, which is reported to be a substrate for several drug transporters and is not metabolized by cytochrome P450 enzymes. Male Sprague-Dawley rats received GTE (400 mg/kg), EGCG (150 mg/kg) or saline (control) by oral gavage, 30 min before a single intragastric administration of 10 mg/kg nadolol. Plasma and urinary concentrations of nadolol were determined using high performance liquid chromatography. Pharmacokinetic parameters were estimated by a noncompartmental analysis. Pretreatment with GTE resulted in marked reductions in the maximum concentration (Cmax) and area under the time-plasma concentration curve (AUC) of nadolol by 85% and 74%, respectively, as compared with control. In addition, EGCG alone significantly reduced Cmax and AUC of nadolol. Amounts of nadolol excreted into the urine were decreased by pretreatments with GTE and EGCG, while the terminal half-life of nadolol was not different among groups. These results suggest that the coadministration with green tea catechins, particularly EGCG, causes a significant alteration in the pharmacokinetics of nadolol, possibly through the inhibition of its intestinal absorption mediated by uptake transporters.

Activation of p38 mitogen-activated protein kinase is required for in vivo brain-derived neurotrophic factor production in the rat hippocampus.

Several lines of evidence strongly suggest that brain-derived neurotrophic factor (BDNF) is associated with the formation, storage and recall of memory in the hippocampus and that it is important to maintain a considerable level of hippocampal BDNF in order to keep normal functions. BDNF can be synthesized in an activity-dependent manner. In fact, kainic acid or AMPA enhances BDNF levels in hippocampal granule neurons. However, the mechanisms of BDNF production are largely unclear. Recently, we have found that riluzole, which blocks voltage-gated sodium channels and thereby reduces glutamate release, actually strengthens immunoreactivity of BDNF in hippocampal granule neurons of rats. Therefore, we examined the riluzole-activated signaling pathways for BDNF production. Riluzole increased levels of phospho-p38 mitogen-activated protein kinase (p38 MAPK), as well as BDNF levels. Inhibition of p38 MAPK by SB203580 reduced riluzole effects, while activation of p38 MAPK by anisomycin increased levels of BDNF, suggesting that p38 MAPK can mediate BDNF production. Riluzole-induced elevation of phospho-activating transcription factor-2, a transcription factor downstream of p38 MAPK, was also observed. A blocker of N-type voltage-gated calcium channels reduced the effects of riluzole on BDNF production and p38 MAPK activation. We also examined a possible involvement of the adenosine A1 receptor in BDNF production because riluzole can influence ecto-nucleotide levels. An A1 receptor agonist inhibited riluzole-induced elevation of BDNF levels, whereas an antagonist not only increased levels of BDNF and active p38 MAPK but also augmented riluzole effects. These results indicate that, in the rat hippocampus, there is an in vivo signaling pathway for BDNF synthesis mediated by p38 MAPK, and that N-type voltage-gated calcium channels and/or adenosine A1 receptors contribute to p38 MAPK activation.

Pathological examination with two-millimetre serial sectioning for sentinel lymph node biopsies in breast cancer.

AIMS: To compare enhanced pathology with serial sectioning and the transcription-reverse transcription concerted reaction (TRC) for detecting sentinel node (SN) metastasis in breast cancer cases. METHODS: In total, 115 SN samples from 32 breast cancer cases were investigated by pathological examination with 2.0-mm serial sectioning and by quantitative analysis of carcinoembryonic antigen messenger RNA with the TRC. RESULTS: The results were concordant in 98.3% of these cases. Two histologically metastatic nodes tested negative by TRC, whereas none tested positive by TRC alone. CONCLUSION: Pathological examination with 2-mm sectioning showed superior performance to TRC under the study conditions.

Detoxification mechanism of heavy metals in marine mammals and seabirds: interaction of selenium with mercury, silver, copper, zinc, and cadmium in liver.

Subcellular distribution of mercury, selenium, silver, copper, zinc, and cadmium was determined in the liver of northern fur seals (Callorhinus ursinus), black-footed albatrosses (Diomedea nigripes), and Dall's porpoises (Phocoenoides dalli). Mercury, selenium, and silver were preferentially accumulated in nuclear, lysosomal, and mitochondrial fraction with an increase in their hepatic concentrations, whereas copper, zinc, and cadmium were accumulated mainly in cytosol with an increase in the hepatic concentrations for all three species. To gain insight into the existing state of the metals, they were extracted with four extractants--sodium dodecylsulfate (SDS); 2-mercaptoethanol; 2-mercaptoethanol + guanidinium thiocyanate; and copper sulfate (CuSO4)--at several concentrations from nuclear, lysosomal, and mitochondrial fraction in liver from a specimen of northern fur seal. Extraction efficiencies of the metals for 2-mercaptoethanol + guanidinium thiocyanate and CuSO4 were much higher than those for SDS and 2-mercaptoethanol. Also, for all individuals of the three species, metals were extracted by the three extractants--2% SDS; 0.25 mol/L 2-mercaptoethanol + 5 mol/L guanidinium thiocyanate; and 0.1 mol/L CuSO4--from nuclear, lysosomal, and mitochondrial fraction of liver. In the northern fur seals with higher concentration of mercury, the molar ratio of selenium to mercury approached unity in the nonextractable fraction of 0.25 mol/L 2-mercaptoethanol + 5 mol/L guanidinium thiocyanate, suggesting the possible formation of mercuric selenide (HgSe) with increasing hepatic concentration. Because the nonextractable content of mercury and its distribution were larger for black-footed albatross than those for the other two species, it was suggested that the black-footed albatross has a stronger ability to form a stable compound(s) of mercury in the liver. It is notable that the existing state of silver was similar to that of mercury as judged by their subcellular distribution and the extraction tests, suggesting that silver also interacted with selenium in the liver of marine animals used in this study.

Role of ATP in the sensitivity to heat and the induction of apoptosis in mammalian cells.

Heat-induced cell death and apoptosis were studied with respect to intracellular ATP. Studies on the relationship between hyperthermic cell-killing at 44 degrees C and cellular ATP levels in four cell lines grown as monolayers and six cell lines grown in suspension showed good correlations between cellular ATP levels and the sensitivity to heat. D(0) values (the dose required to reduce survival in the linear portion of the response by 63%) linearly increased with an increase in cellular ATP levels. No such changes in sensitivity to heat were observed between the cells cultured at different cell densities, regardless of the change in the cellular ATP level. These results suggest that cellular intrinsic ability to supply ATP rather than the level of pooled ATP per se is responsible for the thermal response. Heat-induced apoptosis in L5178Y cells was observed following treatment at 42 degrees C for 70 min, 44 degrees C for 20 min or 47 degrees C for 3 min, which corresponded to surviving fractions of 25, 0.6 and 0.8%, respectively, but not at 47 degrees C for 20 min, indicating that mild heat shock induced apoptosis. 2-deoxyglucose (2DG) and 2,4-dinitrophenol (DNP) increased the sensitivity to heat and affected the mode of cell death. Cells treated with 2DG and DNP (2DG/DNP) were heated at 42 degrees C for 20 min, and then incubated at 37 degrees C for up to 2h in the presence or absence of 2DG/DNP. In the absence of 2DG/DNP, the cellular ATP level recovered to 76% of the control level and DNA ladder formation was observed, whereas in the presence of 2DG/DNP, the cellular ATP level was further decreased (3-7% of the control) and no DNA fragmentation was detected. These results suggest that the inhibition of ATP synthesis is closely associated with the enhancement of sensitivity to heat and that ATP is required for the induction of apoptosis.

[Postoperative chemotherapy with a novel oral anticancer drug composed of tegafur, gimeracil and oteracil potassium to curability C scirrhus type gastric cancer].

We report the a case of 60-year-old male whose final finding was curability C and stage IV scirrhus type gastric cancer because of N3, CY1 and DM (+) treated with a novel oral anticancer drug composed of tegafur (FT), Gimeracil (CDHP) and Oteracil Potassium (Oxo) in a molar ratio of 1:04:1 after operation. This drug was administered orally twice daily after meals at a dose of 80 mg/body/day. One cycle consisted of consecutive administration for 28 days and 14 days rest, and this treatment cycle was repeated twice. Postoperative abdominal CT showed swollen paraaortic lymph nodes regarded as metastasis. However, they were reduced after 1 cycle and remained so. The serum carcinoembryonic antigen (CEA) level had decreased after 1 cycle. The patient's performance status (PS) had also recovered without severe side effects. It was considered that this anticancer drug composed of FT, CDHP and Oxo was effective to scirrhus type gastric cancer and useful as an adjuvant chemotherapy in view of the patient's living quality.

Histamine-induced increase in isometric tension of smooth muscle is mediated by local vagus nerve in human bronchus.

BACKGROUND: The vagus nerve is reported to play an important role in the regulation of airway responsiveness. OBJECTIVE: In the present study, we investigated the role of the local vagus nerve in the changes in isometric tension of smooth muscle induced by histamine in the human airway. METHODS: Eight human lung tissue specimens were obtained at thoracic surgery, and 24 bronchial smooth muscle strips were used for isometric tension recording. The changes in isometric tension were induced by histamine in the presence or absence of physostigmine (10(-6) M), atropine (10(-6) M), and/or tetrodotoxin (10(-6) M). RESULTS: We found that: (1) histamine induced a dose-dependent increase in the isometric tension in human bronchial smooth muscle; (2) physostigmine (10(-6) M) significantly potentiated the amplitude of the histamine-induced increase in isometric tension; (3) atropine (10(-6) M) significantly suppressed the histamine-induced increase in isometric tension; (4) tetrodotoxin (10(-6) M), did not affect the histamine-induced increase in isometric tension of smooth muscle, and (5) in the presence of tetrodotoxin, atropine significantly suppressed the histamine-induced increase in isometric tension. CONCLUSION: These findings suggest that the histamine-induced increase in isometric tension is mediated partly by acetylcholine, presumably released by the direct action of histamine on the vagus efferent nerve terminals without the central reflex via vagus nerve.

[Percutaneous endoscopic gastrostomy (PEG) for the management of dysphagia: experiences in the neurosurgical care unit].

This report concerns percutaneous endoscopic gastrostomy (PEG) administered in the neurosurgical care unit to a patient with dysphasia. This reliable nutrition route has the major advantage of minimal surgical invasion and can be expected to become a standard nutritional method. Since patients with neurological disorders account for the majority of those who need PEG, neurosurgeons need to be aware of the importance of PEG.

Sensitizing effects of gallium citrate on hyperthermic cell killing in vitro.

The lethal effects of gallium citrate in combination with heat were studied using four cell lines, L5178Y, FM3A, P388 and HeLa. Cells were incubated with different concentrations (0.2 2 mM) of gallium citrate at 37 degrees C for 24 h and heated at a range of temperatures from 40-44 degrees C for various time periods up to 6 h in the absence of gallium citrate. Survival and cell viability were determined by clonogenic assay and the dye-exclusion test, respectively. All of the cell lines tested were insensitive to heat below 41 degrees C, but were very sensitive to heat above 43 degrees C. Gallium citrate was cytotoxic to these cell lines at different levels: P388 and HeLa were far more sensitive than L5178Y and FM3A. The killing effects of heat at 41 degrees C were greatly enhanced by gallium citrate in L5178Y and P388 cells. The Arrhenius analysis for the lethal effect of heat, determined by clonogenic assay, in L5178Y cells showed that the transition temperature was remarkably decreased for the gallium-treated cells from approximately 43 degrees C to 41 degrees C. The mechanism for this decrease in the transition temperature may be attributable to the additional effects of gallium citrate on energy metabolism. Preincubation with 0.05 mM gallium citrate at 37 degrees C for 7 days also enhanced heat sensitization at 41 degrees C in L5178Y. This preincubation condition may correspond to the condition for the continuous infusion of gallium that is clinically used for cancer treatment. In contrast, treatment with gallium did not greatly enhance the sensitivity of FM3A or HeLa cells to heat at 41 degrees C, but the effects of gallium were significant.

The biological and clinicopathological characteristics of right-sided colon cancer.

The biological characteristics of right-sided colon cancer were examined in 74 colon cancers with regard to clinicopathological parameters, proliferative activity and p53 expression. Significant differences between right-sided and left-sided colon cancer were found in age, tumor size, histological type and lymphatic vessel invasion. The proliferating cell nuclear antigen labeling index did not significantly differ between the two cancers. The frequency of p53 overexpression was lower in the former than in the latter. The results suggested that right-sided colon cancer did not differ from left-sided colon cancer in proliferative activity except for its tendency to be locally advanced and to differ in carcinogenesis.

Making of a facial perforator map by thermography.

It has been confirmed that thermography is an effective method by which to locate perforators to be used for local flaps. One disadvantage of thermography is its complicated procedure. If it was possible to identify perforators quickly and easily, many operations would be dramatically simplified. The authors' objective was to develop a method of mapping surface perforators using thermography. They pressed a vinyl bag filled with ice water against a test area for 25 seconds and began photographing the area directly after icing. Almost all of the enhanced hot spots appeared for 65 seconds after icing. The number and locations of enhanced perforating vessels varied widely, which they anticipated as a result of differences among individuals, and fluctuations in the measuring environment and the performance of measuring instruments. However, the presence of many perforators is common, and these images are considered to be reliable. Based on their findings, the authors consider the facial perforator map to be accurate and useful. Application of the facial perforator map may simplify many operations and may contribute to making surgery safer and more effective.

Neurally mediated syncope induced by lung cancer--a case report.

The authors present hemodynamic and autonomic features of recurrent and episodic neurally mediated syncope in a man with lung cancer involving afferent vagus. He revealed extreme hypotension with bradycardia occurring during sitting or standing. A head-up tilt test also induced syncope. However, syncope attacks no longer occurred 2 weeks after admission. Alternatively, the paralyses of the left recurrent laryngeal nerve and the left phrenic nerve developed. It is suggested that the lung cancer involved upper rootlets of the left vagus and caused transient hypersensitivity of baroreceptor function that resulted in neurally mediated syncope.

[Chronic dissecting aneurysm of the sinus of valsalva: report of a case].

The subject was a forty five year old female who was admitted to our hospital with chief complaints of cough and thoracic distress. After detailed examination, she was diagnosed as having aneurysm of the noncoronary sinus of Valsalva and aortic regurgitation. The finding during operation showed chronic aortic dissection localized to the noncoronary sinus of Valsalva. The entry of aortic dissection was just above the noncoronary annulus, which was found to be detached and leaned to the left ventricule. An operation for aortic root replacement was performed with Carrel patch method and had a good postoperative course. Only a few reports have been made on cases of aneurysm of the noncoronary sinus of Valsalva caused by chronic regional aortic dissection.

Mouse semaphorin H induces PC12 cell neurite outgrowth activating Ras-mitogen-activated protein kinase signaling pathway via Ca(2+) influx.

We recently showed that mouse semaphorin H (MSH), a secreted semaphorin molecule, acts as a chemorepulsive factor on sensory neurites. In this study, we found for the first time that MSH induces neurite outgrowth in PC12 cells in a dose-dependent manner. Comparison of Ras-mitogen-activated protein kinase (MAPK) signaling pathways between MSH and nerve growth factor (NGF) revealed that these pathways are crucial for MSH action as well as NGF. K-252a, an inhibitor of tyrosine autophosphorylation of tyrosine kinase receptors (Trks), did not inhibit the action of MSH, suggesting that MSH action occurs via a different receptor than NGF. L- and N-types of voltage-dependent Ca(2+) channel blockers, diltiazem and omega-conotoxin, inhibited MSH-induced neurite outgrowth and MAPK phosphorylation in a Ca(2+)-dependent manner. A transient elevation in intracellular Ca(2+) level was observed upon MSH stimulation. These findings suggest that extracellular Ca(2+) influx, followed by activation of the Ras-MAPK signaling pathway, is required for MSH induced PC12 cell neurite outgrowth.

[A case of left atrial thrombus complicated with coarctation of the aorta].

The case was a sixty one year old female who was diagnosed as having acute arterial embolism of right upper arm and underwent embectomy. The detailed examination which followed revealed left atrial myxoma and coarctation of the aorta. Due to the risk of embolism, an emergency operation was performed to install a right axillofemoral bypass with an 8 mm artificial graft. Left atrial myxoma was then excised in an operation using an artificial heart-lung apparatus. Pathological examinations of excised tumor offered no trace of tumor but only of left atrial thrombus. Postoperative results were satisfactory. The pressure difference between upper and lower arms was improved to 0.8 in pressure index from preoperative 0.5 and it became possible to control the blood pressure of upper arm within the level of 130 to 150 mmHg. Axillofemoral bypass is an effective method for a case like the above where a site of coarctation of the aorta cannot be directly repaired.

Pulmonary artery sarcoma diagnosed using intravascular ultrasound images.

Primary and secondary malignant intravascular tumours of the pulmonary artery occur infrequently and the diagnosis is usually delayed as symptoms and findings from conventional examinations are non-specific. The case is presented of a patient with a pulmonary artery sarcoma, probably arising from ribs resected some years previously, in which intravascular ultrasound (IVUS) provided important diagnostic findings.

[Changes in SpO2 during total intravenous anesthesia combined with propofol and SpO2 during one-lung anesthesia ventilation].

We retrospectively examined SpO2 during one-lung anesthesia (OLA). One hundred and fifty patients of ASA 1 or 2 for thoracoscopic surgery were anesthetized with propofol and fentanyl (n = 93) or pentazocine (n = 57) and mechanically ventilated with FIO2 = 0.6 in the lateral decubitus position. Twelve patients (8%) developed SpO2 < or = 95% in the first 20 minutes of OLA. It has been reported that hypoxemia during OLA occurs in 13-40% of patients under inhalation anesthesia with FIO2 = 1.0. Our results show the total intravenous anesthesia using propofol is useful to maintain SpO2 during OLA. SpO2 during OLA tended to fall in the patients for right side operation, with lower SpO2 during two-lung ventilation and higher body mass index (BMI). However BMI has never been reported as a predictor of hypoxemia during OLA. A gravity-dependent mechanism is considered to be more responsible for the dependent regional volume reduction during OLA in patients in the lateral decubitus position.

Dual-isotope SPECT diagnosis of a skull-base metastasis causing isolated unilateral hypoglossal nerve palsy.

We describe a 48-year-old female with an isolated unilateral hypoglossal nerve palsy caused by a skull base metastasis from breast cancer. The patient had a medical history of conservative breast therapy for breast cancer. Although the cause of such a neurological deficit includes various pathologies, the reports focusing on metastatic tumor have been limited in number. Radiologic investigation showed a mass involving both the right hypoglossal canal and the clival edge. Swelling of the hypoglossal nerve was observed in views including its canal. Three-dimensional CT images demonstrated the tumor protruding from the enlarged external orifice of the hypoglossal canal. In the present report we mentioned a nuclear medicine procedure to visualize and characterize the small, abnormal tissue in the skull base. Dual-isotope SPECT confirmed an abnormal uptake of 99mTc-HMDP around the hypoglossal canal and a 201Tl-positive elongated lesion running along the hypoglossal nerve.

Gastroenterological surgery for patients with chronic respiratory insufficiency.

BACKGROUND/AIMS: The aim of this study was to clarify the surgical indications for patients with chronic respiratory insufficiency. METHODOLOGY: Fourteen patients with chronic respiratory insufficiency who underwent abdominal surgical procedures, were retrospectively studied. The surgical indications were carefully determined based primarily on the performance status (PS) of each patient and cardiopulmonary function tests. A PS of equal to or less than 3, which meant the patient's status required bed rest > 50% of the time, and the need for assistance in performing normal activities were all factors considered for surgical indications. RESULTS: During the period studied, two patients were excluded from the surgical indications due to the fact that one was at a terminal stage of pulmonary disease and was completely bedridden (PS = 4), while the other demonstrated active pneumonia with a considerable amount of purulent sputa. Regarding the pulmonary function tests for patients who underwent surgery, the lowest limits of those examinations were as follows: 810 ml of vital capacity (VC), 23.8% of predicted VC, 610 ml of forced expiratory volume in one second (FEV1.0), 38.6% of predicted FEV1.0, 50.5 mmHg of PaO2 while inhaling 4 liters of oxygen and 73.8 mmHg of PaCO2. No surgery related mortality or hospital death within 30 days after operation was observed. Only two patients had cardiopulmonary complications (consisting of pulmonary edema with atrial fibrillation in one patient, and acute myocardial infarction in another patient). However, neither pneumonia, prolonged ventilatory support for more than 2 days, nor the need for a tracheostomy after surgery was observed. CONCLUSIONS: Gastroenterological surgery is thus considered to be indicated even for patients with chronic respiratory insufficiency, as long as the PS can be maintained (PS of equal to or less than 3) and no active pneumonia with a considerable amount of purulent sputa is present.