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1.  Imaging and elemental mapping of biological specimens with a dual-EDS dedicated scanning transmission electron microscope 
Ultramicroscopy  2013;128:24-31.
A dedicated analytical scanning transmission electron microscope (STEM) with dual energy dispersive spectroscopy (EDS) detectors has been designed for complementary high performance imaging as well as high sensitivity elemental analysis and mapping of biological structures. The performance of this new design, based on a Hitachi HD-2300A model, was evaluated using a variety of biological specimens. With three imaging detectors, both the surface and internal structure of cells can be examined simultaneously. The whole-cell elemental mapping, especially of heavier metal species that have low cross-section for electron energy loss spectroscopy (EELS), can be faithfully obtained. Optimization of STEM imaging conditions is applied to thick sections as well as thin sections of biological cells under low-dose conditions at room- and cryogenic temperatures. Such multimodal capabilities applied to soft/biological structures usher a new era for analytical studies in biological systems.
PMCID: PMC3658130  PMID: 23500508
2.  A case of pancreatic ductal adenocarcinoma with marked infiltration with IgG4-positive cells 
A 75-year-old man was diagnosed as having pancreatic ductal carcinoma containing remarkable lymphocytic and plasma cell infiltration, as revealed by the cytological examination of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) specimen. The EUS-FNA specimen showed small amounts of atypical epithelium with noticeable lymphocytes and plasma cells. A pancreatic resection was performed, and the histopathological features showed an invasive pancreatic ductal carcinoma with autoimmune pancreatitis (AIP) lymphoplasmacytic sclerosing pancreatitis (LPSP)-like lesions. Most of the plasma cells were immunoreactive to anti-IgG4 antibody. EUS-FNA may be necessary for the differential diagnosis of AIP and pancreatic cancer, and close attention should be given to the presence of marked lymphoplasmacytic cells in EUS-FNA specimens while making the diagnosis.
PMCID: PMC3643362  PMID: 23661941
Adenocarcinoma; autoimmune pancreatitis; endoscopic ultrasound guided fine-needle aspiration; IgG4
4.  Inhibition of the transient receptor potential cation channel TRPM2 by 2-aminoethoxydiphenyl borate (2-APB) 
British Journal of Pharmacology  2008;153(6):1324-1330.
Background and purpose:
Transient receptor potential melastatin 2 (TRPM2) is a non-selective Ca2+-permeable cation channel and is known to be activated by adenosine 5′-diphosphoribose (ADP-ribose) and hydrogen peroxide. TRPM2 current responses are reported to be drastically potentiated by the combination of each of these ligands with heat. Furthermore, the combination of cyclic ADP-ribose with heat also activates TRPM2. Although flufenamic acid, antifungal agents (miconazole and clotrimazole), and a phospholipase A2 inhibitor (N-(p-amylcinnamoyl)anthranilic acid) inhibit TRPM2, their inhibition was either gradual or irreversible.
Experimental approach:
To facilitate future research on TRPM2, we screened several compounds to investigate their potential to activate or inhibit the TRPM2 channels using the patch-clamp technique in HEK293 cells, transfected with human TRPM2.
Key results:
2-aminoethoxydiphenyl borate (2-APB) exhibited a rapid and reversible inhibition of TRPM2 channels that had been activated by its ADP-ribose or cADP-ribose and heat in a dose-dependent manner (IC50 about 1 μM). 2-APB also inhibited heat-evoked insulin release from pancreatic islets, isolated from rats.
Conclusions and implications:
2-APB proved to be a powerful and effective tool for studying the function of TRPM2.
PMCID: PMC2275460  PMID: 18204483
TRPM2; 2-APB; insulin
5.  Proteomic analysis of stage I primary lung adenocarcinoma aimed at individualisation of postoperative therapy 
British Journal of Cancer  2008;98(3):596-603.
Although postoperative adjuvant chemotherapy (PAC) with uracil–tegafur significantly improves the prognosis of patients with stage I lung adenocarcinoma, subset analysis has revealed that only 11.5% of patients with stage IB derive actual benefit from such therapy. Therefore, it is extremely important to identify patients for whom adjuvant chemotherapy will be beneficial. We performed comprehensive protein analysis of 24 surgically resected specimens of stage I adenocarcinoma using liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by bioinformatical investigations to identify protein molecules. Furthermore, we carried out immunohistochemical studies of 90 adenocarcinoma specimens to validate the results of LC-MS/MS. We detected two kinds of protein molecules (myosin IIA and vimentin) by LC-MS/MS. We confirmed their immunohistochemical expression and distribution, and evaluated the relationship between the expression of these proteins and prognosis after adjuvant chemotherapy. Patients with no expression of either myosin IIA or vimentin showed a significantly better outcome regardless of PAC using uracil–tegafur. However, we were unable to select responders to uracil–tegafur using these proteins. Cases of adenocarcinoma lacking expression of either myosin IIA or vimentin show a good outcome without PAC, and therefore do not require such treatment.
PMCID: PMC2243141  PMID: 18212748
myosin IIA; vimentin; postoperative adjuvant chemotherapy; responder to uracil–tegafur; stage I lung adenocarcinoma
6.  Delirium During Intravenous Sedation With Midazolam Alone and With Propofol in Dental Treatment 
Anesthesia Progress  2006;53(3):95-97.
A 62-year-old man visited our clinic for dental implantation under intravenous sedation. He demonstrated increased psychomotor activity and incomprehensible verbal contact during intravenous sedation. Although delirium caused by midazolam or propofol in different patients has been reported, the present case represents a delirium that developed from both drugs in the same patient, possibly because of the patient's smaller tolerance to midazolam and propofol.
PMCID: PMC1693665  PMID: 17175823
Delirium; Midazolam; Propofol; Dental treatment
7.  New diagnostic marker for sepsis: soluble CD14 subtype 
Critical Care  2004;8(Suppl 1):P191.
PMCID: PMC4099778
8.  Modulation of basal nitric oxide-dependent cyclic-GMP production by ambient glucose, myo-inositol, and protein kinase C in SH-SY5Y human neuroblastoma cells. 
Journal of Clinical Investigation  1996;97(3):736-745.
Defective tissue perfusion and nitric oxide production and altered myo-inositol metabolism and protein kinase C activation have been invoked in the pathogenesis of diabetic complications including neuropathy. The precise cellular compartmentalization and mechanistic interrelationships of these abnormalities remain obscure, and nitric oxide possesses both neurotransmitter and vasodilator activity. Therefore the effects of ambient glucose and myo-inositol on nitric oxide-dependent cGMP production and protein kinase C activity were studied in SH-SY5Y human neuroblastoma cells, a cell culture model for peripheral cholinergic neurons. D-Glucose lowered cellular myo-inositol content, phosphatidylinositol synthesis, and phosphorylation of an endogenous protein kinase C substrate, and specifically reduced nitric oxide-dependent cGMP production a time- and dose-dependent manner with an apparent IC50 of approximately 30 mM. The near maximal decrease in cGMP induced by 50 mM D-glucose was corrected by the addition of protein kinase C agonists or 500 microM myo-inositol to the culture medium, and was reproduced by protein kinase C inhibition or downregulation, or by myo-inositol deficient medium. Sodium nitroprusside increased cGMP in a dose-dependent fashion, with low concentrations (1 microM) counteracting the effects of 50 mM D-glucose or protein kinase C inhibition. The demonstration that elevated D-glucose diminishes basal nitric oxide-dependent cGMP production by myo-inositol depletion and protein kinase C inhibition in peripheral cholinergic neurons provides a potential metabolic basis for impaired nitric oxide production, nerve blood flow, and nerve impulse conduction in diabetes.
PMCID: PMC507111  PMID: 8609230
9.  Risk factors to cause tooth formation anomalies in chemotherapy of paediatric cancers 
European Journal of Cancer Care  2013;22(3):353-360.
This study aimed to investigate the risk factors of tooth formation anomalies in anti-cancer chemotherapies. Long-term survivors treated by conventional chemotherapy (n = 26), conventional chemotherapy with high-dose chemotherapy (HDC) (n = 14), and HDC with total body irradiation (TBI) (n = 6) were analysed for the incidence of tooth agenesis, microdonts, and short-rooted teeth. The tooth agenesis and/or microdonts were found in second premolars and second molars, but not in first molars or central incisors. The ratio of subjects with tooth agenesis and/or microdonts was 66.7% and 18.2% in subjects administered conventional chemotherapy at <4 years and ≥4 years of age, respectively, while it was 100% and 25% in subjects administered HDC at <4 years and ≥4 years of age. The incidence of tooth formation anomalies did not related with the duration of conventional chemotherapy but increased by HDC. The incidence of tooth formation anomalies did not show significantly differences between the HDC with and without TBI groups, and was higher in busulfan-administered subjects than in subjects given cyclophosphamide. It may be concluded that the high-risk group of tooth agenesis is the subjects with HDC under 4 years of age. However, protocols of conventional chemotherapy are not an important risk factor to cause the tooth formation anomalies.
PMCID: PMC3655612  PMID: 23336315
growth and development; medical disability; orthodontics; tooth formation anomalies; anti-cancer chemotherapy

Results 1-9 (9)