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Notes: We fabricated submicron-sized intrinsic Josephson junctions by the focused-ion-beam (FIB) etching method. The principal result was a reduction of the in-plane junction area to 0.3 μm2 by direct FIB etching with no degradation in the critical transition temperature (Tc). In the current (I)–voltage (V) characteristics of these stacks, the gap structure and the normal state resistance are clearly observed together with a reduction of the Joule heating and disappearance of the branch structure. The Coulomb staircase structure was found in the I–V curves of submicron junctions as a result of their small effective capacitance of fF order. © 1999 American Institute of Physics.

Notes: An episode of fever, cough, shortness of breath and leucocytosis developed in a 31-year-old atopic housewife from mould exposure in her home environment is evaluated. A chest radiograph revealed diffuse tiny nodular infiltrations in both whole lung fields. Spirometry revealed a severe restrictive type of ventilation impairment. Bronchoalveolar lavage (BAL) showed an increased lymphocyte count with reversed CD4 +/CD8 + ratio and transbronchial lung biopsy showed markedly increased lymphocytic infiltration in alveolar septa. Fungal cultures in the air of her home were positive for Penicillium expansum and other fungi. Double immunodiffusion test with the patient's serum showed two precipitin bands to P. expansum antigens. Her symptoms, abnormal findings of radiograph, and spirometric abnormalities disappeared after 2 months' avoidance. The serum precipitin disappeared after 1 month's avoidance. This study indicates that the patient had hypersensitivity pneumonitis (HP) on exposure to P. expansum in her home environment.

Notes: Capsaicin has been shown the different biologic and toxic effects on the non-neuronal celIs and serveral transformed cells. The present study aimed at evaluating the cytotoxic mechanism of capsacin on the cultured human skin fibroblast. Normal neonatal human fibroblasts were used for MTT assay to measure the changes of celI survival, while growth factors, receptor antagonist, antioxidants and calcium modulators were pretreated or co-treated with capsaicin. Fibroblast survival was significantly stimulated with EGF (10 ng/ml), bFGF (10 ng/ml) and capsazepine (10 µm) but inhibited by cycloheximide (1 µg/ml). When 200 µm capsaicin is given to fibroblasts, chromatin condensations were observed at 12 h, and cell survival rate was reduced to 25–50% at 24 h. Vanilloid receptor antagonists, capsazepine and ruthenium red did not prevent the toxic effect of capsaicin, and 10 µm capsazepine rather paradoxically enhanced the cytotoxicity. In contrast to bFGF (10 ng/ml), EGF (10, 100 ng/ml) enhanced the cytotoxicity of capsaicin. Neuropeptides, substance P (1, 10 nm) and CGRP (1, 10 nm), and a structural analogue to capsaicin, tyrosine (0.3–1.2 mm) did not affect the cytotoxicity. However, antioxidants trolox (100 µm) and ascorbic acid (0.1, 0.3 mm) reduced the capsaicin cytotoxicity. Of calcium-modulating agents, nifedifine, a Ca2+ channel blocker (10, 20 µm) and cyclopiazonic acid, a Ca2+-ATPase inhibitor in ER (10 µm) did not influence the cytotoxicity, but BAPTA/AM as a chelater for cytoplasmic free calcium ion (10 µm) significantly decreased capsaicin cytotoxicity. Unlike cycloheximide, a protein synthesis inhibitor, z-VAD-FMK, a non-specific caspase inhibitor, prevented the capsaicin cytotoxicity. The DNA ladder and TUNEL-positive cells were observed from the capsaicin-treated fibroblasts and Western blot revealed caspase-3 activity. Thus, capsaicin-induced cytotoxicity on human skin fibroblasts is more likely to suggest the mechanism of apoptotic pathway where antioxidants may play a role to prevent it.

Notes: : Whey protein isolate (5% w/v) films were plasticized with sorbitol or glycerol, and candelilla wax (0.8% w/ v) was added to produce whey protein isolate and candelilla wax emulsion edible films. The films were cut into 7.62 cm × 2.54 cm strips and evaluated by a 15-member trained sensory panel for milk odor, transparency/opaqueness, sweetness, and adhesiveness using a structured 9-point intensity scale. The films had no distinctive milk odor; however, they were perceived to be slightly sweet and adhesive by the trained sensory panel. Whey protein isolate films without candelilla wax were clear and transparent, whereas candelilla wax containing films were opaque.

Notes: Background: We report a case of hypersensitivity pneumonitis (HP) in a 17-year-old male student caused by Fusarium napiforme found in his home environment. Methods: The patient was diagnosed according to history, chest radiograph, spirometry, high-resolution chest CT, and transbronchial lung biopsy. To identify the causative agent, cultured aeromolds were collected by the open-plate method. From the main fungi cultured, fungal antigens were prepared, and immunoblot analysis with the patient's serum and each fungal antigen was performed. Results: Five fungal species were isolated from the patient's home. Immunoblotting analysis with the patient's serum demonstrated more than 10 IgG-binding fractions to F. napiforme extract only, while little binding was noted with the other fungal antigens. Conclusions: We should be aware that HP may be caused by F. napiforme in the home environment.

Notes: Aims:  PTEN is a recently identified tumour suppressor inactivated in a wide variety of human cancers, including endometrial cancers. Mutation of the PTEN tumour suppressor gene has been reported in approximately 50–83% of endometrial adenocarcinoma. Despite this fact, study of the expression of PTEN protein in human tumours is limited. PTEN protein functions as a tumour suppressor by regulating the cell cycle and survival through signal transduction pathway. PTEN protein was considered to have a dual-specificity phosphatase activity, but it is now known that its principal physiological activity is mainly derived from its lipid phosphatase activity. The cyclin-dependent kinase inhibitor, p27, has been suggested as a downstream target of cell cycle arrest of PTEN in various in vitro studies. In this study, we evaluated the alteration of PTEN protein expression in endometrial carcinoma and assessed its relationship to the expression of p27, the presumed downstream target of PTEN.Methods and results:  Immunohistochemical staining was performed on 66 cases of endometrial carcinoma including 61 endometrioid type and five serous type, using antibodies to PTEN and p27. Loss or decrease of PTEN expression was observed in 66% (40/61 cases) of uterine endometrioid carcinoma, whereas most uterine serous carcinoma (4/5 cases) showed intense PTEN expression. Four (30%) of 13 endometrial hyperplasia synchronous with endometrioid carcinoma demonstrated complete loss of PTEN expression. All endometrioid carcinoma synchronous with PTEN-negative endometrial hyperplasia showed loss of PTEN expression. Alteration of PTEN expression was not correlated with histological grade or stage. Decreased immunoreactivity of p27 was found in 48 cases (79%) of 61 endometrioid carcinoma, and 76% (36 cases) of them also showed loss or decrease of PTEN expression. Four of five uterine serous carcinoma revealed strong p27 immunoreactivity, all of which showed intense PTEN expression. A positive correlation between PTEN and p27 expression was statistically significant (Mantel–Haenszel χ2 test, P=0.001). Immunoreactivity of p27 was not related to histological grade and clinical stage.Conclusion:  These results show that PTEN and p27 are differentially expressed in endometrioid type carcinoma compared with those of the serous type, and suggest that the cyclin-dependent kinase inhibitor, p27, is a downstream target of PTEN-dependent cell cycle arrest in endometrial carcinoma.

Notes: Downregulation of TGF-β receptors is implicated in colon cancer development. Inactivation of either of the two transmembrane serine/threonine kinases, TGF-β1 types I/II receptors, is now implicated in carcinogenesis, especially gastrointestinal carcinogenesis.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:We generated transgenic mice, called pS2–dnRII or ITF–dnRII, of which the dominant negative mutant of the TGF-β type II receptor was expressed under the control of tissue-specific promoters, the pS2 promoter for stomach and ITF for intestine. They were either infected with H.pylori (ATCC 43504 strain, CagA+ and VacA+) or administered with azoxymethane to determine the significance of loss of TGF-β signalling in gastrointestinal carcinogenesis.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Gastric adenocarcinoma developed in pS2–dnRII mice, whereas only chronic active gastritis was noted in wild-type littermates after 36 weeks of H.pylori infection. Mice lacking in TGF-β signalling specifically in the stomach showed a significantly higher proliferation cell nuclear antigen-labelling index when infected with H.pylori than wild-type littermates (P 〈 0.01). Development of colonic aberrant crypt foci was provoked in mice by intraperitoneal injections of azoxymethane, and ITF–dnRII mice showed significantly higher incidences of ACF and colon cancers than wild-type littermates.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:Maintaining normal TGF-β signalling in the gastrointestinal tract seems to be important either for preventing abnormal mucosal proliferation, or for suppressing or retarding carcinogenesis.