Frequent activating HRAS mutations in trichilemmoma.

BACKGROUND: Trichilemmoma is a benign follicular epithelial tumour exhibiting outer root sheath differentiation. It is associated with Cowden syndrome and naevus sebaceus (NS), but the pathogenesis of sporadic tumours is poorly understood. Recently, NS was found to be caused by postzygotic HRAS or KRAS mutations. OBJECTIVES: We sought to determine whether NS-related and NS-unrelated trichilemmomas harbour RAS mutations. METHODS: Formalin-fixed and paraffin-embedded blocks of 12 NS-related and 15 NS-unrelated trichilemmomas from 26 individuals were retrieved and analysed to determine the presence of mutations in exons 1 and 2 of the HRAS, KRAS and NRAS genes by polymerase chain reaction and direct sequencing. Mutational hotspots of the FGFR3 and PIK3CA genes were also analysed for NS-unrelated cases. RESULTS: Among the 27 cases, mutually exclusive HRAS c.37G>C and c.182A>G mutations were observed in 17 and three tumours, respectively. Of the 12 NS-related tumours, 11 (92%) harboured the HRAS c.37G>C substitution. Of the 15 sporadic tumours, nine (60%) harboured HRAS mutations, including six c.37G>C and three c.182A>G. An HRAS c.182A>G mutation was observed only in sporadic tumours. No mutations were observed in the other genes that were tested. CONCLUSIONS: The high frequency of HRAS activating mutations, including the c.182A>G substitution, which was rather rare in NS, suggests that most trichilemmomas are authentic neoplasms.

Immunostaining of glutamine synthetase is a sensitive and specific marker for diagnosing focal nodular hyperplasia in needle biopsy.

AIMS: Focal nodular hyperplasia (FNH) has characteristic histological features which may not be seen in needle biopsy specimens. We investigate the diagnostic role of glutamine synthetase (GS) in needle biopsy specimens. METHODS: Sixty-one hepatic tumours were categorised into 20 'definite' FNHs, 13 'probable' FNHs, and 28 cases without specific diagnosis. Needle biopsy specimens of 92 non-tumourous lesions, 25 well-differentiated hepatocellular carcinomas (WDHCCs), and 4 high-grade dysplastic nodules (HGDNs) and resection specimens of 10 macroregenerative nodules were also selected for immunohistochemical stain of GS for comparison. RESULTS: All 20 'definite' FNHs, nine 'probable' FNHs, and five cases without specific diagnosis expressed typical map-like staining pattern of GS. The demographic data of these five cases were similar to those of FNH. All cases of chronic hepatitis B and C, cirrhosis, macroregenerative nodule and peritumourous liver tissue showed normal pericentral/periseptal pattern. Fifteen of 25 WDHCCs and one HGDN showed diffuse pattern. Ten WDHCCs and two HGDNs showed negative staining. One HGDN showed mosaic pattern. CONCLUSIONS: Immunohistochemical staining of GS increases the diagnostic sensitivity of FNH in needle biopsy, especially in those without typical morphology. It also helps in differentiating FNH from other tumourous and non-tumourous lesions.

Effects of a Chinese medical herbs complex on cellular immunity and toxicity-related conditions of breast cancer patients.

Rose geranium (Pelargonium graveolens, Geraniaceae) has anti-cancer and anti-inflammatory properties, and promotes wound healing. Similarly, Ganoderma tsugae (Ganodermataceae), Codonopsis pilosula (Campanulaceae) and Angelica sinensis (Apiaceae) are traditional Chinese herbs associated with immunomodulatory functions. In the present study, a randomised, double-blind, placebo-controlled study was conducted to examine whether the Chinese medicinal herb complex, RG-CMH, which represents a mixture of rose geranium and extracts of G. tsugae, C. pilosula and A. sinensis, can improve the immune cell count of cancer patients receiving chemotherapy and/or radiotherapy to prevent leucopenia and immune impairment that usually occurs during cancer therapy. A total of fifty-eight breast cancer patients who received chemotherapy or radiotherapy were enrolled. Immune cell levels in patient serum were determined before, and following, 6 weeks of cancer treatment for patients receiving either an RG-CMH or a placebo. Administration of RG-CMH was associated with a significant reduction in levels of leucocytes from 31·5 % for the placebo group to 13·4 % for the RG-CMH group. Similarly, levels of neutrophils significantly decreased from 35·6 % for the placebo group to 11·0 % for the RG-CMH group. RG-CMH intervention was also associated with a decrease in levels of T cells, helper T cells, cytotoxic T cells and natural killer cells compared with the placebo group. However, these differences between the two groups were not statistically significant. In conclusion, administration of RG-CMH to patients receiving chemotherapy/radiotherapy may have the capacity to delay, or ease, the reduction in levels of leucocytes and neutrophils that are experienced by patients during cancer treatment.

Transvenous embosurgery of a left sigmoid sinus dural arteriovenous fistula via a retrograde approach from the superior ophthalmic vein, cavernous and inferior petrosal sinuses.

The efficacy and safety of transvenous embosurgery for sigmoid sinus dural arteriovenous fistula (DAVF) using the internal jugular vein approach is well known. Embosurgery of cavernous sinus DAVF has also been described utilizing a superior ophthalmic vein approach. The first report of a sigmoid sinus DAVF endosurgical repair via a superior ophthalmic vein approach in a patient without internal jugular vein access is presented.

Space charge effects in field emission nanodevices.

Electron field emission from a single nanoemitter is a barrier tunneling, quantum mechanical process that can, therefore, be described by the well-known Fowler-Nordheim (FN) equation. At high emission current densities, however, the space charge caused by the cathode may affect the current density-voltage (J-V) characteristics predicted by the FN theory. In this study, we theoretically investigated the effect of space charge on FE nanodevices, including diode and triode structures. The J-V characteristics of FE nanodevices were obtained by analytically (diode structures) or numerically (triode structures) solving the coupled FN equation and Poisson's equation. We discuss the behavior of FE nanodiodes and nanotriodes displaying different geometries, dimensions and work functions of their emitter materials. In the high current density region, space charge plays an important role in FE nanodevices; the threshold current density of space-charge limitation is related to the electric field distributions. Besides, our theoretical results are in good agreement with the experimental results reported previously.

Synthesis design of artificial magnetic metamaterials using a genetic algorithm.

In this article, we present a genetic algorithm (GA) as one branch of artificial intelligence (AI) for the optimization-design of the artificial magnetic metamaterial whose structure is automatically generated by computer through the filling element methodology. A representative design example, metamaterials with permeability of negative unity, is investigated and the optimized structures found by the GA are presented. It is also demonstrated that our approach is effective for the synthesis of functional magnetic and electric metamaterials with optimal structures. This GA-based optimization-design technique shows great versatility and applicability in the design of functional metamaterials.

Effects of silymarin on the resolution of liver fibrosis induced by carbon tetrachloride in rats.

Silymarin, a standardized extract of the milk thistle (Silybum marianum), has a long tradition as a herbal remedy, and was introduced as a hepatoprotective agent a few years ago. However, the therapeutic effects of silymarin remain undefined. Carbon tetrachloride (CCl4) is a xenobiotic used extensively to induce oxidative stress and is one of the most widely used hepatic toxins for experimental induction of liver fibrosis in the laboratory. In this study, we investigated the restoration of the CCl4-induced hepatic fibrosis by high dose of silymarin in rats. After treatment with oil (as normal group; n = 6) or CCl4 [as model (n = 7) and therapeutic (n = 7) groups] by intragastric delivery for 8 weeks for the induction of liver fibrosis, the rats in the normal and model group were administered orally normal saline four times a week for 3 weeks whilst the therapeutic group received silymarin (200 mg/kg). The histopathological changes were observed with Masson staining. The results showed that the restoration of the CCl4-induced damage of liver fibrosis in the therapeutic group was significantly increased as compared to that in the model group. Moreover, silymarin significantly decreased the elevation of aspartate aminotransferase (AST), alanine aminotransferase, and alkaline phosphatase in serum, and also reversed the altered expressions of alpha-smooth muscle actin in liver tissue. Therefore, these findings indicated that silymarin may have the potential to increase the resolution of the CCl4-induced liver fibrosis in rats.

A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival.

The role of DNA methylation and of the maintenance DNA methyltransferase Dnmt1 in the epigenetic regulation of developmental stage- and cell lineage-specific gene expression in vivo is uncertain. This is addressed here through the generation of mice in which Dnmt1 was inactivated by Cre/loxP-mediated deletion at sequential stages of T cell development. Deletion of Dnmt1 in early double-negative thymocytes led to impaired survival of TCRalphabeta(+) cells and the generation of atypical CD8(+)TCRgammadelta(+) cells. Deletion of Dnmt1 in double-positive thymocytes impaired activation-induced proliferation but differentially enhanced cytokine mRNA expression by naive peripheral T cells. We conclude that Dnmt1 and DNA methylation are required for the proper expression of certain genes that define fate and determine function in T cells.

Toxic effects of six plant oils alone and in combination with controlled atmosphere on Liposcelis bostrychophila (Psocoptera: Liposcelididae).

Six plant essential oils alone as repellent and fumigant, and in combination with the controlled atmosphere against Liposcelis bostrychophila Badonnel were assessed in the laboratory. These essential oils were extracted from the leaves of six source plants: Citrus tangerina Tanaka, Citrus aurantium L., Citrus bergamia Risso et Poiteau, Pinus sylvestris L., Cupressus funebris End]., and Eucalyptus citriodora Hook. The repellency test indicated that L. bostrychophila adults were repelled by filter paper strips treated with six essential oils. Of these essential oils, the C. funebris oil was most effective followed by that of F. sylvestris, C. tangerina, C. bergamia, and E. citriodora. The average repellency of the C. aurantium oil against L. bostrychophila adults was significantly lower than other five test oils by day 14. These essential oils had a high level of toxicity in the fumigation assay against L. bostrychophila adults at both 10 and 20 ppm. When combined with two controlled atmosphere treatments (12% CO2 + 9% O2, and 10% CO2 + 5% O2, balanced N2), the toxicity of plant oils was enhanced significantly.

A triply templated artificial beta-sheet.

This paper describes the design, synthesis, and structural evaluation of a compound (4) comprising three molecular templates and a peptide strand that mimics a three-stranded protein beta-sheet. Two of the templates mimic the hydrogen-bonding functionality of peptide beta-strands and serve as the top and bottom strands by embracing the peptide strand, which is located in the middle of the sheet. The remaining template holds the three strands next to each other. The synthesis of artificial beta-sheet 4 begins with the bottom template and involves the sequential addition of the middle and top strands. (1)H NMR chemical shift and NOE studies establish that this compound folds to adopt a hydrogen-bonded beta-sheetlike structure in CDCl(3) solution. Chemical shift studies indicate that triply stranded artificial beta-sheet 4 is more tightly folded than its smaller doubly stranded homologue, artificial beta-sheet 1.

Significantly increased cortisol secretion in normal adrenocortical cells transfected with K-ras mutants derived from human functional adrenocortical tumors.

Our previous study showed that the mutation hotspots of the K-ras proto-oncogene in human functional adrenocortical tumors are in codons 15, 16, 18, and 31, thus differing from the sites in other tumors. In addition, analyzing the K-Ras protein by a recombinant DNA technique showed that the activity of endogenic GTPase and the GTPase-activating protein (GAP)-binding ability were significantly decreased in patients with these tumors. The aim of this study was to understand whether those K-ras mutants, which were found only in human adrenocortical tumors, play an important role in these tumors. Thus, the mutant K-ras cDNA was constructed with mammalian expression vectors and transfected into normal adrenocortical cells. The amount of cortisol secreted by the transfected cells was 20 to 30 times that of normal cells. Furthermore, Northern blot analysis revealed that the expression of the three steroidogenesis-related genes P450(scc) (cholesterol side-chain cleavage enzyme), P450(C17) (17alpha-hydroxylase/17, 20-lyase), and P450(C21) (steroid 21-hydroxylase) gene increased in the transfected cells. The K-ras oncogene significantly increases cortisol secretion by normal adrenocortical cells.

Significance of salivary epidermal growth factor in peptic ulcer disease in hemodialysis patients.

BACKGROUND/AIMS: Hemodialysis (HD) patients are prone to developing peptic ulcers. However, of all the risk factors associated with peptic ulcers, none have been shown to be more prevalent in HD patients than in the general population. However, salivary epidermal growth factor (EGF) may play a role in peptic ulcer diseases. METHODS: Salivary EGF levels and bioactivities were assayed in 47 maintenance HD patients and 30 normal controls, and the molecular weights of EGF were assessed using high-performance liquid chromatography (HPLC). RESULTS: Salivary EGF levels were not different between both groups of subjects (4.2 +/- 0.34 vs. 5 +/- 0.54 ng/mg protein, NS), and HPLC revealed that salivary EGF in both groups had similar molecular weights. However, salivary EGF bioactivity was significantly depressed in the HD patients as compared to the normal controls (0.59 +/- 0.08 vs. 1.55 +/- 0.15 ng/mg protein, p < 0.01). Stepwise multiple regression showed that the low salivary EGF levels were associated with female gender (p < 0.05), while low salivary EGF bioactivity was associated with HD per se (p < 0.05). In the 22 HD patients who underwent gastric endoscopy, salivary EGF bioactivity was significantly lower in those with peptic ulcers than in those without (0.38 +/- 0.08 vs. 0.69 +/- 0.08 ng/mg protein, p < 0.05). CONCLUSION: Decreased salivary EGF bioactivity may contribute to peptic ulcer disease among maintenance HD patients.

Insulin and heparin suppress superoxide production in diabetic rat glomeruli stimulated with low-density lipoprotein.

Patients with diabetic nephropathy frequently show increased levels of circulating low-density lipoprotein (LDL) and oxidized LDL, which have been reported to be related to the generation of oxygen-free radicals. In the present study, we evaluated the effects of insulin and heparin on the superoxide production of glomeruli, which were isolated from rats with streptozotocin-induced diabetes for one week, one month, and three months, respectively, and the glomeruli were stimulated with native and oxidized LDL. LDL was isolated from normal subjects with normolipidemia, and the superoxide was measured by using a spectrophotometer. The results demonstrated that the poorly controlled diabetic rat glomeruli showed a significantly higher production of superoxide than normal glomeruli under basal status and after stimulation, and this production increased further with the progression of diabetes. Insulin suppressed both the basal and stimulated production of superoxide in diabetic glomeruli, but not in normal glomeruli. Heparin suppressed superoxide production of diabetic glomeruli stimulated by either native or oxidized LDL, and it also partly suppressed superoxide production of normal glomeruli stimulated by oxidized LDL. Our results suggest that glomerular injury in diabetics with hyperlipidemia may be mediated through enhanced generation of oxygen-free radicals, which can be partially attenuated by insulin and heparin.

Tunnel study of on-road vehicle emissions and the photochemical potential in Taiwan.

Motor vehicle emission factors of carbon monoxide (CO) and non-methane volatile organic compounds (NMVOCs) were calculated inside the Chung-Cheng Tunnel of Kaohsiung in Taiwan. The results were compared with those model predictions from the Mobile Taiwan 2.0 model. Individual concentrations of 21 species of NMVOCs were also determined. Photochemical potential of NMVOCs was evaluated by using the maximum incremental reactivity (MIR). Field data showed that the integrated emission factors of CO and NMVOCs for actual fleet were 6.3 and 1.5 g/veh km, respectively. The error range of these factors may be up to 45%. The predicted values by the Mobile Taiwan 2.0 model closely matched the observed data. Concentrations of isopentane, 2-methylpentane, toluene and m,p-xylene were the dominant species of NMVOCs. The ratio of maximum incremental reactivity to NMVOCs concentration was 3.9, similar to those of the studies in the US Fort McHenry and Tuscarora Tunnel.

Development, survival and reproduction of black citrus aphid, Toxoptera aurantii (Hemiptera: Aphididae), as a function of temperature.

The development, survival, and reproduction of the black citrus aphid Toxoptera aurantii (Boyer de Fonscolombe) were evaluated at ten constant temperatures (4, 7, 10, 15, 20, 25, 28, 30, 32 and 35 degrees C). Development was limited at 4 and 35 degrees C. Between 7 and 32 degrees C, developmental periods of immature stages varied from 44.2 days at 7 degrees C to 5.3 days at 28 degrees C. Overall immature development required 129.9 degree-days above 3.8 degrees C. The upper temperature thresholds of 32.3, 28.6, 29.3, 27.2, and 28.6 degrees C were determined from a non-linear biophysical model for the development of instars 1-4 and overall immature stages, respectively. Immature survivorship varied from 82.1 to 97.7% within the temperature range of 10-30 degrees C. However, immature survivorship was reduced to 26.3% at 7 degrees C and 33.1% at 32 degrees C. Mean adult longevity was the longest (44.2 days) at 15 degrees C and the shortest (6.2 days) at 32 degrees C. The predicted upper temperature limit for adult survivorship was at 32.3 degrees C. Total nymph production increased from 16.3 nymphs per female at 10 degrees C to 58.7 nymphs per female at 20 degrees C, declining to 6.1 nymphs per female at 32 degrees C. The estimation of lower and upper temperature limits for reproduction was at 8.2 and 32.5 degrees C, respectively. The population reared at 28 degrees C had the highest intrinsic rate of increase (0.394), the shortest population doubling time (1.8 days), and shortest mean generation time (9.5 days) compared with the populations reared at six other temperatures. The population reared at 20 degrees C had the highest net reproductive rate (54.6). The theoretical lower and upper temperature limits for population development, survival and reproduction were estimated at 9.4 and 30.4 degrees C, respectively. The biology of T. aurantii was also compared with three other citrus aphid species.

Thyroid metastasis from intraductal papillary-mucinous carcinoma of the pancreas. A case report.

BACKGROUND: Intraductal papillary-mucinous carcinoma (IPMC) of the pancreas is a newly identified clinicopathologic entity of the exocrine pancreas. It has been considered a slowly growing and less-aggressive carcinoma with a favorable prognosis. There have been only a few documents reporting its distant metastasis and cytologic features, with no report of thyroid metastasis until the present. CASE: A case of IPMC occurred in a 45-year-old male, who was admitted with rapid growth and tenderness of the thyroid. Abdominal computed tomography showed the typical cystic dilatation of IPMC with adjacent organ metastasis. Fine needle aspiration of the thyroid yielded papillary fronds of carcinoma cells with nuclear pleomorphism, abundant cytoplasm and prominent nucleoli in a mucinous background. Immunohistochemical findings from the skin and thyroid characterized the papillary-mucinous carcinoma as having originated in the pancreas. CONCLUSION: This case suggests that papillary carcinoma fronds aspirated from the thyroid should be further differentiated from the primary site and that a pleomorphic nucleus in a mucinous background is a useful feature to exclude a thyroid origin. Before this, distant metastasis of IPMC to the skin and thyroid has not been reported. The prognosis of IPMC with wide, distant metastasis at an advanced stage is poor.

Alteration in the expression of protein kinase C isoforms in human hepatocellular carcinoma.

This study was designed to investigate the alterations of individual protein kinase C (PKC) isoforms in human liver cancer. Surgical specimens of hepatocellular carcinoma and adjacent normal tissues were extracted into cytosolic and membranous fractions. The level of membrane-bound PKCalpha in the cancer tissue was significantly lower than that in the adjacent normal tissue and consistent with the change in PKC activity. In addition, there was a significant negative correlation between PKCalpha and tumor size. In both cytosolic and membrane fractions, levels of PKCdelta and PKCzeta was significantly higher in the cancer tissue than those in the adjacent normal liver tissue. The alterations in the PKC isoforms signify their roles in the hyperproliferation in liver cancer.

Sex differences in relation to serum hepatitis B e antigen and alanine aminotransferase levels among asymptomatic hepatitis B surface antigen carriers.

This study aimed to investigate sex differences in relation to hepatitis B e antigen (HBeAg) and serum alanine aminotransferase (ALT) levels in chronic asymptomatic hepatitis B virus (HBV) infection. HBeAg and ALT level were determined in 636 asymptomatic hepatitis B surface antigen carriers. There was no significant sex differences in the age-adjusted prevalence of HBeAg. Abnormal ALT level (>45 IU/l) was more frequent in carriers with HBeAg (17.5% vs 7.6%; P = 0.001). Multivariate analysis indicated that male sex (odds ratio, 2.0; 95% confidence interval, 1.1-3.6) and HBeAg (odds ratio, 2.6; 95% confidence interval, 1.6-4.3) were independent risk factors for abnormal ALT levels. Male sex and HBeAg-positivity are independent risk factors for abnormal ALT activity in chronic HBV infection. This observation may be related to sex differences in chronic HBV infection.

Diffusion of hydrogen sulfide and methyl mercaptan onto microporous alkaline activated carbon.

Activated carbon kinetic studies show that both H2S and CH3SH yielded pore diffusion coefficients from 10(-6) to 10(-8) cm2/s. Results indicated that pore structures could influence effective diffusivity. Under the same adsorbate concentration, CH3SH exhibited a greater effective pore diffusion coefficient than H2S. This may be attributed to the fact that CH3SH has both polar (-SH) and non-polar (-CH3) functional groups and dissolves into water easier, thus providing more attraction for the activated carbon surface. In addition, the saturation vapor pressure of CH3SH is lower than that of H2S. Therefore, CH3SH is easier to adsorb onto activated carbon than H2S.