bluuebunny/crossref_metadata_2025 huggingface dataset:
Volatile components of leaves and flowers of periwinkle Catharanthus roseus (L.) G. Don from New Delhi
Authors: Pandey‐Rai Shashi , Mallavarapu Gopal Rao , Naqvi A. A. , Yadav Anju , Rai Sanjay Kumar , Srivastava Suchi , Singh Digvijay , Mishra Raghvendra , Kumar Sushil
Published: February 2006

The hydrodistilled waxy oils of the leaves and flowers of Catharanthus roseus (L.) G. Don cv. Nirmal plants grown at New Delhi were analysed by GC and GC–MS. A total of 52 compounds were identified, accounting for the 91.3% of the leaf oil. Among these the main constituents were as follows: (E,E)‐2,4‐hexadienal (7.7%), citronellol (7.9%), geraniol (7.9%), p‐cresol (4.7%), (Z,E)‐pentadecanal (6.6%), hexadecanoic acid (4.9%), palmitic acid (4.9%) and phytol (6.4%). A total of 41 compounds were identified, accounting for 99.4% of the flower oil, whose main constituents were heneicosane (20.8%), tricosane (37.9%), tetracosane (6.1%) and docosane (4.3%). A total of 24 compounds occurred in both the leaf and flower oils. Copyright © 2006 John Wiley & Sons, Ltd.
Volatile constituents of the leaves and flowers of Salvia przewalskii Maxim. from Tibet
Authors: Liu Jimei , Nan Peng , Tsering Qiong , Tsering Tashi , Bai Zhankui , Wang Li , Zhijun Liu  , Zhong Yang
Published: February 2006

The composition of the volatile oils obtained from the leaves and flowers of Salvia przewalskii Maxim. grown in Tibet was analysed by gas chromatography–mass spectrometry (GC–MS) for the first time. Totals of 43 compounds were identified in the leaf oil and 69 compounds in the flower oil. A comparative study of the oil composition from the leaves and flowers found 22 common constituents of these oils, viz. α‐thujene, β‐phellandrene, linalool, terpinene‐4‐ol, diisopropenyl methyl vinyl cyclohexane, caryophyllene, germacrene D, borneol, caryophyllene oxide, spathulenol, germacrene B, δ‐cadinene, humulene, farnesane, α‐cadinol, β‐caryophyllene, elemene, sabinene hydrate, γ‐terpinene, p‐cymene, camphene and α‐pinene. The percentages of the most components were higher in the leaf oil than in the flower oil, especially those of β‐phellandrene and caryophyllene (26.08% and 11.11%, respectively). Farnesene, chamigrene, n‐hexadecane, epicedrol, cyclotetradecane, n‐octadecane, 9‐octadecen‐1‐ol, 1‐heneicosyl formate, Z‐8‐hexadecen‐1‐ol acetate, n‐heneicosane and n‐pentacosane were the specific constituents found only in the flower oil, while β‐cadinol was the specific constituent found only in the leaf oil. Copyright © 2006 John Wiley & Sons, Ltd.
Studies on essential oils, Part 41. Chemical composition, antifungal, antioxidant and sprout suppressant activities of coriander (Coriandrum sativum) essential oil and its oleoresin
Authors: Singh Gurdip , Maurya Sumitra , de Lampasona M. P. , Catalan Cesar A. N.
Published: February 2006

Gas chromatography–mass spectrometry (GC–MS) analysis of the seed oil of coriander (Coriandrum sativum) showed the presence of 52 components, accounting for 98.45% of the total oil. The major components were linalool (75.30%), geranyl acetate (8.12%) and α‐pinene (4.09%). Its oleoresin showed the presence of 28 components. Oleic acid (36.52%), linoleic acid (33.2%) and palmitic acid (11.05%) were the major components. The antifungal activities of coriander oil and its oleoresin against eight fungi were evaluated using the inverted petriplate and food poison techniques. Using the inverted petriplate method, the essential oil was found to be highly active against Curvularia palliscens, Fusarium oxysporum, Fusarium moniliforme and Aspergillus terreus. In the case of the oleoresin, more than 50% mycelial zone inhibition was obtained for the fungi Fusarium oxysporum, Aspergillus niger and Aspergillus terreus. Using the food poison technique, the essential oil showed 100% inhibition on the growth of A. terreus, A. niger, F. graminearum and F. oxysporum, whereas its oleoresin showed weaker fungitoxic activity, exhibiting 100% inhibition on the growth of F. oxysporum only. The oleoresin had a better antioxidant activity for sunflower oil than essential oil and synthetic antioxidants, BHA and BHT. The oil was also found to exert strong sprout suppressant activity (SSA) for potatoes. Copyright © 2006 John Wiley & Sons, Ltd.
Composition of the essential oil of white sage, Salvia apiana
Authors: Borek Theodore T. , Hochrien James M. , Irwin Adriane N.
Published: February 2006

The essential oil of white sage, Salvia apiana, was obtained by steam distillation and analysed by GC–MS. A total of 13 components were identified, accounting for >99.9% of the oil. The primary component was 1,8‐cineole, accounting for 71.6% of the oil. Published in 2006 by John Wiley & Sons, Ltd.
Dendritic cells take up viral antigens but do not support the early steps of hepatitis B virus infection
Authors: Untergasser Andreas , Zedler Uta , Langenkamp Anja , Hösel Marianna , Quasdorff Maria , Esser Knud , Dienes Hans-Peter , Tappertzhofen Barbara , Kolanus Waldemar , Protzer Ulrike
Published: February 2006

Dendritic cells (DC) of hepatitis B virus (HBV) carriers have been reported to exhibit functional impairment. Possible explanations for this phenomenon are infection of HBV by DC or alteration of DC function by HBV. We therefore analyzed whether DC support the different steps of HBV infection and replication: uptake, deposition of the HBV genome in the nucleus, antigen expression, and progeny virus release. When HBV genomes were artificially introduced into monocyte-derived DC by adenoviral vectors, low-level expression of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) but no HBV replication was detected. When monocyte-derived DC were subjected to wild-type HBV or a recombinant HBV expressing

Renilla

luciferase under a non–liver-specific promoter, intracellular HBV DNA was detected in a low percentage of cells. However, neither nuclear cccDNA was formed nor luciferase activity was detected, indicating that either uncoating or nucleocytoplasmic transport were blocked. To verify our observation in the

in vivo

situation, myeloid and plasmacytoid DC were isolated from blood of high viremic HBV carriers, and analyzed by quantitative polymerase chain reaction (PCR) and electron microscopy. Although circulating DC had

in vivo

been exposed to more than 104 HBV virions per cell, HBV genomic DNA was hardly detected, and no nuclear cccDNA was detected at all. By using electron microscopy, subviral particles were found in endocytic vesicles, but virions were undetectable as were viral capsids in the cytoplasm.

In conclusion

, circulating DC may take up HBV antigens, but neither support nucleocytoplasmic transport nor replication of HBV. (Hepatology 2006;43:539–547.)
Enhanced cell survival of Hep3B cells by the hepatitis B x antigen effector, URG11, is associated with upregulation of β-catenin
Authors: Lian Zhaorui , Liu Jie , Li Li , Li Xianxing , Clayton Marcy , Wu Meng-Chao , Wang Hong-Yang , Arbuthnot Patrick , Kew Michael , Fan Daiming , Feitelson Mark A.
Published: February 2006

Intrahepatic expression of hepatitis B x antigen (HBxAg) is associated with the development of hepatocellular carcinoma (HCC), perhaps through

trans

-activation of selected cellular genes. When this was examined by PowerBlot analysis, upregulated levels of β-catenin and several known β-catenin effectors were observed in HBxAg-positive compared with HBxAg-negative HepG2 cells. When HBxAg was introduced into Hep3B cells, upregulated expression of wild-type β-catenin was observed. This was also observed in Hep3B cells overexpressing the HBxAg upregulated gene, URG11. Upregulated expression of URG11 and β-catenin correlated with HBxAg

trans

-activation function. Transient transfection assays with fragments of the β-catenin promoter showed that it was activated by both HBxAg and URG11 and inhibited by URG11-specific small inhibitory RNA. The latter also inhibited the growth of Hep3BX cells in a serum-free medium, which correlated with depressed levels of β-catenin. Activation of β-catenin effector genes was observed in cells stably expressing HBxAg or overexpressing URG11 compared with control cells transfected with the pTOPFLASH reporter plasmid. Extensive costaining between HBxAg, URG11, and β-catenin was observed in infected liver and HCC nodules, suggesting a close relationship

in vivo

.

In conclusion

, wild-type β-catenin is activated by HBxAg, in part, through the upregulated expression of the HBxAg effector URG11. URG11 stimulates the β-catenin promoter and hepatocellular growth and survival. These observations also suggest that URG11 may be a regulatory element in the β-catenin signaling pathway and may be a target for chemoprevention of HCC. (Hepatology 2006;43:415–424.)
HDAC inhibitor treatment of hepatoma cells induces both TRAIL-independent apoptosis and restoration of sensitivity to TRAIL
Authors: Pathil Anita , Armeanu Sorin , Venturelli Sascha , Mascagni Paolo , Weiss Thomas S. , Gregor Michael , Lauer Ulrich M. , Bitzer Michael
Published: February 2006

Hepatocellular carcinoma (HCC) displays a striking resistance to chemotherapeutic drugs or innovative tumor cell apoptosis–inducing agents such as tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). Recently, we found 2 histone deacetylase inhibitors (HDAC-I), valproic acid and ITF2357, exhibiting inherent therapeutic activity against HCC. In TRAIL-sensitive cancer cells, the mechanism of HDAC-I–induced cell death has been identified to be TRAIL-dependent by inducing apoptosis in an autocrine fashion. In contrast, in HCC-derived cells, a prototype of TRAIL-resistant tumor cells, we found a HDAC-I-mediated apoptosis that works independently of TRAIL and upregulation of death receptors or their cognate ligands. Interestingly, TRAIL resistance could be overcome by a combinatorial application of HDAC-I and TRAIL, increasing the fraction of apoptotic cells two- to threefold compared with HDAC-I treatment alone, whereas any premature HDAC-I withdrawal rapidly restored TRAIL resistance. Furthermore, a tumor cell–specific downregulation of the FLICE inhibitory protein (FLIP) was observed, constituting a new mechanism of TRAIL sensitivity restoration by HDAC-I. In contrast, FLIP levels in primary human hepatocytes (PHH) from different donors were upregulated by HDAC-I. Importantly, combination HDAC-I/TRAIL treatment did not induce any cytotoxicity in nonmalignant PHH.

In conclusion

, HDAC-I compounds, exhibiting a favorable

in vivo

profile and inherent activity against HCC cells, are able to selectively overcome the resistance of HCC cells toward TRAIL. Specific upregulation of intracellular FLIP protein levels in nonmalignant hepatocytes could enhance the therapeutic window for clinical applications of TRAIL, opening up a highly specific new treatment option for advanced HCC. (Hepatology 2006;43:425–434.)
Increased prevalence of primary biliary cirrhosis near superfund toxic waste sites
Authors: Ala Aftab , Stanca Carmen M. , Bu-Ghanim Moueen , Ahmado Imad , Branch Andrea D. , Schiano Thomas D. , Odin Joseph A. , Bach Nancy
Published: February 2006

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are uncommon liver diseases of unknown etiology. Reported clustering of PBC cases may be due to environmental factors. Individuals with PBC have a high prevalence of thyroid disease and thyroid disease is reportedly more prevalent near Superfund toxic waste sites (SFS). The objective of this study was to examine the prevalence and potential clustering of individuals with PBC and PSC near SFS. De-identified clinical and demographic data were used to determine the observed prevalence for each New York City zip code (n = 174) and borough (n = 5) of patients with PBC (PBC-OLT) or PSC (PSC-OLT) who were listed for liver transplantation. The expected prevalence was calculated using Organ Procurement and Transfer Network (OPTN) and U.S. Census data. Both PBC-OLT patients and patients not listed for liver transplantation (PBC-MSSM) were included in the cluster analysis. Prevalence ratios of PBC-OLT and PSC-OLT cases were compared for each zip code and for each borough with regard to the proximity or density of SFS, respectively. SaTScan software was used to identify clusters of PBC-OLT cases and PBC-MSSM cases. Prevalence ratio of PBC-OLT, not PSC-OLT, was significantly higher in zip codes containing or adjacent to SFS (1.225 vs. 0.670, respectively,

P

= .025). The borough of Staten Island had the highest prevalence ratio of PBC-OLT cases and density of SFS. Significant clusters of both PBC-OLT and PBC-MSSM were identified surrounding SFS.

In conclusion

, toxin exposure may be a risk factor influencing the clustering of PBC cases. (Hepatology 2006;43:525–531.)
Ascorbic acid improves the intrahepatic endothelial dysfunction of patients with cirrhosis and portal hypertension
Authors: Hernández-Guerra Manuel , García-Pagán Juan C. , Turnes Juan , Bellot Pablo , Deulofeu Ramón , Abraldes Juan G. , Bosch Jaime
Published: February 2006

Patients with cirrhosis show intrahepatic endothelial dysfunction, characterized by an impaired flow-dependent vasorelaxation. This alteration is responsible for the marked postprandial increase in portal pressure and is attributed to an insufficient release of nitric oxide (NO). Ascorbic acid reverts endothelial dysfunction in other vascular disorders, via the increase of NO bioavailability through the neutralization of superoxide anions, thus preventing the scavenging of NO by superoxide. This study examined whether acute ascorbic acid administration might improve endothelial dysfunction in cirrhosis. Thirty-seven portal hypertensive patients with cirrhosis had measurements of hepatic and systemic hemodynamics, ascorbic acid, and malondialdehyde (MDA). Patients were randomly allocated to receive ascorbic acid (3 g, intravenously, n = 15) or placebo (n = 12) followed by a liquid meal. A third group received ascorbic acid followed by a sham meal (n = 10). Measurements were repeated after 30 minutes (hepatic venous pressure gradient at 15 and 30 minutes). Patients with cirrhosis had significantly lower ascorbic acid levels and higher MDA than healthy controls. Ascorbic acid significantly reduced MDA levels and markedly attenuated the postprandial increase in the hepatic venous pressure gradient (4% ± 7% vs. 18% ± 10% in placebo at 30 minutes,

P

< .001). Ascorbic acid followed by sham meal did not modify hepatic or systemic hemodynamics.

In conclusion

, patients with cirrhosis exhibited intrahepatic endothelial dysfunction, associated with decreased levels of ascorbic acid and increased levels of MDA. Ascorbic acid improved intrahepatic endothelial dysfunction, blunting the postprandial increase in portal pressure. These results encourage the performance of further studies testing antioxidants as adjunctive therapy in the treatment of portal hypertension. (Hepatology 2006;43:485–491.)
Zonal gene expression in murine liver: Lessons from tumors
Authors: Hailfinger Stephan , Jaworski Maike , Braeuning Albert , Buchmann Albrecht , Schwarz Michael
Published: February 2006

Gene expression in hepatocytes within the liver lobule is differentially regulated along the portal to central axis; however, the mechanisms governing the processes of zonation within the lobule are unknown. A model for zonal heterogeneity in normal liver is proposed, based on observations of differential expression of genes in liver tumors from mice that harbor activating mutations in eitherCatnb(which codes for β-catenin) orHa-ras. According to the model, the regulatory control consists of two opposing signals, one delivered by endothelial cells of the central veins activating a β-catenin–dependent pathway (retrograde signal), the other by blood-borne molecules activating Ras-dependent downstream cascades (anterograde signal).In conclusion, gradients of opposing signaling molecules along the portocentral axis determine the pattern of enzymes and other proteins expressed in hepatocytes of the periportal and pericentral domains of the liver lobule. (Hepatology 2006;43:407–414.)
Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis in vivo
Authors: Zhan Shan-Shan , Jiang Joy X. , Wu Jian , Halsted Charles , Friedman Scott L. , Zern Mark A. , Torok Natalie J.
Published: February 2006

Hepatic stellate cell activation is a main feature of liver fibrogenesis. We have previously shown that phagocytosis of apoptotic bodies by stellate cells induces procollagen α1 (I) and transforming growth factor beta (TGF-β) expression

in vitro

. Here we have further investigated the downstream effects of phagocytosis by studying NADPH oxidase activation and its link to procollagen α1 (I) and TGF-β1 expression in an immortalized human stellate cell line and in several models of liver fibrosis. Phagocytosis of apoptotic bodies in LX-1 cells significantly increased superoxide production both in the extracellular and intracellular milieus. By confocal microscopy of LX-1 cells, increased intracellular reactive oxygen species (ROS) were detected in the cells with intracellular apoptotic bodies, and immunohistochemistry documented translocation of the NADPH oxidase p47phox subunit to the membrane. NADPH oxidase activation resulted in upregulation of procollagen α1 (I); in contrast, TGF-β1 expression was independent of NADPH oxidase activation. This was also confirmed by using siRNA to inhibit TGF-β1 production. In addition, with EM studies we showed that phagocytosis of apoptotic bodies by stellate cells occurs

in vivo

.

In conclusion,

these data provide a mechanistic link between phagocytosis of apoptotic bodies, production of oxidative radicals, and the activation of hepatic stellate cells.

Supplementary material for this article can be found on the HEPATOLOGY website (

http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html

).

(Hepatology 2006;43:435–443.)
The use of vasoconstrictors in patients with cirrhosis: Type 1 HRS and beyond
Authors: Moreau Richard , Lebrec Didier
Published: February 2006

In patients with cirrhosis and type 1 hepatorenal syndrome (HRS), systemic vasodilation, which is mainly attributable to splanchnic vasodilation, plays a critical role in the activation of endogenous vasoconstrictor systems, resulting in renal vasoconstriction and functional renal failure. It has been suggested that the use of splanchnic (and systemic) vasoconstrictors such as terlipressin (a vasopressin analog) or alpha-1-adrenoceptor agonists (midodrine or noradrenaline) may improve renal function in patients with type 1 HRS. Six studies (with only one randomized study in a small series of patients) have shown that terlipressin improves renal function in these patients. However, there is evidence that terlipressin alone may be less effective than terlipressin combined with intravenous albumin in improving renal function. Future randomized studies should confirm this difference and evaluate the impact of terlipressin therapy (with or without intravenous albumin) on survival. Interestingly, in nonrandomized studies, the use of alpha-1 agonists combined with other therapies (octreotide and albumin for midodrine; furosemide and albumin for noradrenaline) has been shown to improve renal function in patients with type 1 HRS. The efficacy and safety of combined therapies including alpha-1 agonists should be confirmed in randomized studies. Finally, preliminary evidence suggests that vasoconstrictor administration may be a novel therapeutic approach targeting vasodilation involved in the mechanism of: (1) renal failure in type 2 HRS; (2) paracentesis-induced circulatory dysfunction; and (3) arterial hypotension induced by byproducts of gram-negative bacteria. Further studies are needed in all these fields. (Hepatology 2006;43:385–394.)
Drug-induced liver injury: Summary of a single topic clinical research conference
Authors: Watkins Paul B. , Seeff Leonard B.
Published: February 2006

Idiosyncratic drug induced liver injury (DILI) remains poorly understood. It is assumed that the affected individuals possess a rare combination of genetic and non genetic factors that, if identified, would greatly improve understanding of the underlying mechanisms. This single topic conference brought together basic scientists, translational investigators, and clinicians with an interest in DILI. The goal was to define high priority areas of investigation that will soon be made possible by The Drug-Induced Liver Injury Network (DILIN). Since 2004 DILIN has been collecting clinical data, genomic DNA and some tissues from patients who have experienced bone fide DILI. The presentations spanned many different areas of DILI, and included novel data concerning mechanisms of hepatotoxicity, new “omics” approaches, and the challenges of improving causation assessment. (Hepatology 2006;43:618–631.)
Cardif: A protein central to innate immunity is inactivated by the HCV NS3 serine protease
Authors: Evans Jared D. , Seeger Christoph
Published: February 2006

Antiviral immunity against a pathogen is mounted upon recognition by the host of virally associated structures. One of these viral ‘signatures’, double-stranded (ds) RNA, is a replication product of most viruses within infected cells and is sensed by Toll-like receptor 3 (TLR3) and the recently identified cytosolic RNA helicases RIG-I (retinoic acid inducible gene I, also known as Ddx58) and Mda5 (melanoma differentiation-associated gene 5, also known as Ifih1 or Helicard 1.) Both helicases detect dsRNA, and through their protein-interacting CARD domains, relay an undefined signal resulting in the activation of the transcription factors interferon regulatory factor 3 (IRF3) and NF-κB. Here we describe Cardif, a new CARD-containing adaptor protein that interacts with RIG-I and recruits IKK-α, IKK-β and IKK-ε kinases by means of its C-terminal region, leading to the activation of NF-κB and IRF3. Overexpression of Cardif results in interferon-β and NF-κB promoter activation, and knockdown of Cardif by short interfering RNA inhibits RIG-I-dependent antiviral responses. Cardif is targeted and inactivated by NS3-4A, a serine protease from hepatitis C virus known to block interferon-β production. Cardif thus functions as an adaptor, linking the cytoplasmic dsRNA receptor RIG-I to the initiation of antiviral programmes.
gnuplot 4.0: a portable interactive plotting utility
Authors: Racine Jeff
Published: February 2006

gnuplot, under active development since 1986, is an interactive plotting utility for UNIX, IBM OS/2, MS Windows, DOS, Apple Macintosh, VMS, Atari and many other platforms. It is free and open source, though it is not licensed under the GPL, nor is it GNU software. gnuplot supports a number of ‘terminal’ types including interactive screen terminals, pen plotters, printers, and pseudo‐devices like LATEX, metafont, pdf, svg, and bitmap png. As of version 4.0 it also incorporates nonlinear regression routines (formerly gnufit). This software may be of interest to econometricians, particularly those who use LATEX in their work. Copyright © 2006 John Wiley & Sons, Ltd.
‘Type’ in morphology and phylogeny
Authors: Rieppel Olivier
Published: February 2006

Comparative morphologists, developmental biologists, as well as paleontologists, recognize the existence of ‘types,’ or ‘Baupläne,’ in nature, marked out by a certain ‘sameness’ of structure that prevails through all variation in shape and function. The ‘sameness’ that marks out ‘types’ is one of structural correspondence (topology and connectivity), which is believed to be causally rooted in ontogeny (developmental constraints). In an evolutionary context, the structural relations that mark out ‘types’ are explained as relations of homology. The use of concepts such as ‘type’ or ‘Bauplan’ has been criticized from a ‘populational thinking’ point of view as being incompatible with current evolutionary theory. The present article explores the contrasting viewpoints, and concludes that current evolutionary theory can accommodate the concept of a ‘type’ in the sense of a ‘homeostatic property cluster natural kind.’ The ‘homeostatic property cluster natural kind’ is a nonessentialistic concept that allows the kind to be historically delimited. J. Morphol. © 2006 Wiley‐Liss, Inc.
Myelin protein zero: Mutations in the cytoplasmic domain interfere with its cellular trafficking
Authors: Konde Viren , Eichberg Joseph
Published: February 2006

The cytoplasmic domain of myelin protein zero (MPZ), the principal protein of peripheral myelin, undergoes phosphorylation on several serine residues and a tyrosine group that is maximal during peak nerve myelination. Mutations that could affect MPZ phosphorylation cause the inherited neuropathy, Charcot‐Marie‐Tooth disease Type 1B. To investigate a possible role for phosphorylation in regulation of MPZ trafficking within the cell, we expressed wild‐type and mutated MPZ‐enhanced green fluorescent protein (GFP) fusion proteins in cultured Schwann‐like cells. Whereas wild‐type protein is present almost entirely at the cell surface, mutation of serine 204 to alanine or at a nearby presumed PKC substrate motif (198RSTK201) causes 40–60% of protein to be retained in the cytoplasm. Mutation of S204 to aspartate, which introduces a permanent negative charge, also impairs MPZ movement to the plasma membrane. In contrast, tyrosine 191 mutation has no effect on MPZ cellular distribution. Simultaneous alteration of S204 and Y191 produces much less perturbation of MPZ trafficking than mutation of S204 alone. Colocalization studies showed that mutated MPZ‐EGFP trapped in the cytoplasm associates with all organelles in the secretory pathway. Previous studies have shown that cytoplasmic mutations at serine, but not tyrosine phosphorylation sites, abolish MPZ adhesive properties. Our results suggest that this loss of adhesion may be due, at least in part, to a failure of sufficient MPZ to reach the cell surface and that this impaired trafficking is associated with deficient serine phosphorylation in the cytoplasmic domain. © 2006 Wiley‐Liss, Inc.
NF‐κB mediated glucocorticoid response in the inner ear after acoustic trauma
Authors: Tahera Yeasmin , Meltser Inna , Johansson Peter , Bian Zhao , Stierna Pontus , Hansson Anita C. , Canlon Barbara
Published: February 2006

The inner ear of humans and experimental animals demonstrate an abundance of glucocorticoid receptors (GR). Glucocorticoids (GC) are widely used to treat different hearing disorders; yet the mechanisms of GC action on the inner ear are unknown. We demonstrate how GR can directly modulate hearing sensitivity in response to a moderate acoustic trauma that results in a hearing loss (10–30 dB). The GC agonist (dexamethasone) and the drugs (metyrapone + RU 486) showed opposing effects on hearing threshold shifts. GC agonist (dexamethasone) decreased the hearing threshold whereas pre‐treatment with a GC synthesis inhibitor (metyrapone) in combination with a GR antagonist (RU 486) exacerbated auditory threshold shifts (25–60 dB) after acoustic trauma with statistically significant increase in GR mRNA and GR protein compared with the vehicle and acoustic trauma group. Acoustic trauma caused a significant increase in the nuclear transport of NF‐κB, whereas pre‐treatment with the drugs (metyrapone and RU 486) blocked NF‐κB nuclear transport into spiral ganglion nuclei. An NF‐κB inhibitor, pyrrolidine dithiocarbamate ammonium blocked the trauma‐induced translocation of NF‐κB and resulted in a hearing loss (45–60) dB. These results indicate that several factors define the responsiveness of the inner ear to GC, including the availability of ligand or receptor, and the nuclear translocation of GR and NF‐κB. These findings will further our understanding of individual GC responsiveness to steroid treatment, and will help improve the development of pharmaceuticals to selectively target GR in the inner ear for individuals with increased sensitivity to acoustic trauma. © 2006 Wiley‐Liss, Inc.
Mechanosensitivity of voltage‐gated K+ currents in rat trigeminal ganglion neurons
Authors: Piao Lin , Ying Li Hai , Park Chul‐Kyu , Cho Ik‐Hyun , Piao Zheng Gen , Jung Sung Jun , Choi Se‐Young , Lee Sung Joong , Park Kyungpyo , Kim Joong‐Soo , Oh Seog Bae
Published: February 2006

We investigated the mechanosensitivity of voltage‐gated K+ channel (VGPC) currents by using whole‐cell patch clamp recording in rat trigeminal ganglion (TG) neurons. On the basis of biophysical and pharmacological properties, two types of VGPC currents were isolated. One was transient (IK,A), the other sustained (IK,V). Hypotonic stimulation (200 mOsm) markedly increased both IK,A and IK,V without affecting their activation and inactivation kinetics. Gadolinium, a well‐known blocker of mechanosensitive channels, failed to block the enhancement of IK,A and IK,V induced by hypotonic stimulation. During hypotonic stimulation, cytochalasin D, an actin‐based cytoskeletal disruptor, further increased IK,A and IK,V, whereas phalloidin, an actin‐based cytoskeletal stabilizer, reduced IK,A and IK,V. Confocal imaging with Texas red‐phalloidin showed that actin‐based cytoskeleton was disrupted by hypotonic stimulation, which was similar to the effect of cytochalasin D. Our results suggest that both IK,A and IK,V are mechanosensitive and that actin‐based cytoskeleton is likely to regulate the mechanosensitivity of VGPC currents in TG neurons. © 2006 Wiley‐Liss, Inc.
Recovery at the terminal ileum of some legume non‐nutritional factors in cannulated pigs
Authors: Rubio Luis A , Pedrosa Mercedes M , Cuadrado Carmen , Gelencser Eva , Clemente Alfonso , Burbano Carmen , Muzquiz Mercedes
Published: February 2006

In order to exert an effect, either local or systemic, putative beneficial dietary substances have to survive at least to some extent the digestive process within the gastrointestinal tract. For that purpose, five castrated male pigs (100 ± 2 kg mean live b.w.) fitted with T‐shaped ileal cannulas were used to determine the recovery up to the terminal ileum of various non‐nutritional factors (NNF) from legumes (defatted soybean, raw lupin, raw chickpea and raw or autoclaved kidney beans). Kidney bean lectin (PHA) recovery within the small intestine ranged between 2.5 and 4.8 mg from 5.96 mg ingested. Two different methods were used to determine ileal digestibility of protease inhibitors (PI) in pigs. According to the enzyme‐linked immunosorbent assay (ELISA) method, apparent digestibility of Kunitz trypsin inhibitor and Bowman–Birk inhibitor for pigs fed the defatted soybean‐based diet were 0 and 58%, respectively. On the other hand, the apparent digestibility of PI along the small intestine, expressed in terms of trypsin inhibitory activity, was 96, 98 and 95% of activity in the diet, while data expressed in terms of chymotrypsin inhibitory activity were 95, 99 and 79% of activity in the diet for defatted soybean, raw chickpea and autoclaved kidney bean diets respectively. Differences found in ileal digestibility values of PI using both methodologies, ELISA and enzymatic inhibition, might be explained by the detection of inactive forms by specific antibodies. Intestinal apparent digestibility of phytate was 0% for defatted soybean and autoclaved kidney bean diets, whereas values for raw lupin and chickpea diets were 4.1 and 24.5%, respectively. In conclusion, significant amounts of several NNF survived the passage through the stomach and small intestine of cannulated pigs, which might have biological relevance. Copyright © 2006 Society of Chemical Industry
Rectal cancer surgery in the elderly: A multivariate analysis of outcome risk factors
Authors: Bufalari Andrea , Giustozzi Giammario , Burattini Maria Federica , Servili Stefano , Bussotti Claudia , Lucaroni Elena , Ricci Enrica , Sciannameo Francesco
Published: February 2006

Background and Objectives

Geriatric population life expectancy is rapidly increasing and the impact of major surgical procedures is not well defined. The purpose of this study was to compare short term surgical results assessing mortality and morbidity and long‐term survival and disease‐free interval in elective rectal surgery patients older than 65 years of age. The main independent risk factors of mortality, morbidity, and overall and disease‐free survival were also identified.

Methods

Out of 177 rectal cancer accepted consecutively from 1991 to 2002, we studied the main clinical and pathological parameters comparing patients older and younger than 65 years. Data have been collected in a database and variables considered were studied by univariate analysis; independent predictive factors of 30‐day mortality and morbidity were identified by multiple logistic regression analysis. Overall, cancer specific and disease‐free survival curves were obtained with the Kaplan–Meier method and results compared with the log‐rank test. Independent risk factors of overall and disease‐free survival have been identified by multivariate logistic regression analysis.

Results

In patients younger and older than 65 years postoperative mortality (3.2% vs. 9.6%) and morbidity (30% vs. 29%) were not significantly different. Variables independently associated with 30‐day mortality were the duration of surgical procedures and postoperative complications. The Kaplan–Meier survival curves showed a significantly worst overall survival (P = 0.003), cancer specific survival (P = 0.02), and disease‐free survival (P = 0.03) in patients aged 65 years or more. Multivariate analysis showed that pT, grading, preoperative CEA level, gender, and site of the tumor along the rectum, the number of blood transfusion and the age group of more than 65 years are independent risk factors for both overall survival and disease‐free interval. The presence of residual disease was an adjunctive factor of overall survival, whereas the Astler and Coller staging was a risk factor for the disease‐free survival.

Conclusion

The short‐term prognosis for elective rectal cancer procedure in patients over 65 years of age was comparable to that of younger patients, whereas long term cancer‐related survival was statistically worst in older patients. J. Surg. Oncol. 2006;93: 173–180. © 2006 Wiley‐Liss, Inc.
Role of dynamic sentinel node biopsy in penile cancer: Our experience
Authors: Perdonà S. , Autorino R. , Gallo L. , Di Lorenzo G. , Cascini G.L. , Lastoria F. , Marra L. , De Sio M. , Damiano R. , Gallo A.
Published: February 2006

Background and Objectives

We report our initial experience with a relatively new technique, the so‐called “dynamic sentinel node biopsy”, in patients with penile cancer.

Methods

From January 2001 to February 2003, 17 consecutive patients with bilateral, clinically node negative penile cancer were enrolled. Dynamic sentinel node biopsy was followed by local excision of the primary lesion or penile amputation during the same session. Standard inguinal node dissection was performed 4 weeks after the first operation in all the patients.

Results

Pre‐operative lymphoscintigraphy revealed no sentinel nodes in 1, unilateral sentinel nodes in 5, and bilateral in 11 patients. Metastases were noted in 5 out of 16 patients (31.25%), bilaterally in 3 of them. Among the five patients with sentinel node metastasis, this was the only tumor positive lymph node in one patient. In all cases with negative dynamic sentinel node biopsy, no metastatic nodes were found at the following inguinal node dissection. Therefore, the technique showed a 100% negative predictive value and an 88% sensitivity.

Conclusions

We believe that dynamic sentinel node biopsy is a minimally invasive procedure that can be easily performed. The goal is to offer the possibility of less extensive surgery for selected low risk patients. J. Surg. Oncol. 2006;93: 181–185. © 2006 Wiley‐Liss, Inc.
Liver resections in over‐75‐year‐old patients: Surgical hazard or current practice?
Authors: Aldrighetti Luca , Arru Marcella , Catena Marco , Finazzi Renato , Ferla Gianfranco
Published: February 2006

Objectives

To assess the safety of hepatic resections in the very old patient by comparing the outcome in patients younger and older than 75 years.

Methods

Thirty‐two resections in 31 patients ≥75 years (Over‐75 Group) were compared with 164 resections in 162 patients <75 years (Control Group). Indications for resection, concomitant diseases, previous abdominal surgery, type of resection, associated surgical procedures, use/length of portal clamping, intra‐operative blood losses and transfusions, and length of operation were preliminarily compared. The outcome was evaluated in terms of post‐operative mortality, morbidity, transfusions, and postoperative hospitalization.

Results

Mean age was 76.0 ± 2.3 years (range 75–83) in the Over‐75 Group and 58.4 ± 10.7 years (range 23–74) in the Control Group. The over‐75 group included more hepatomas (43.8% vs. 26.8%, P = 0.09), chronic liver disease (31.3% vs. 28.7%, P = 0.03) and concomitant diseases (62.5% vs. 32.9%, P = 0.002). The two groups were comparable (P = n.s.) when evaluated for all other variables. The 30‐day mortality rate was 3.6% in the Control Group and none in the Over‐75 Group. Postoperative surgical complications occurred in 37 patients (22.6%) in the Control Group and 1 patient (3.1%) in the Over‐75 Group, with statistically significant differences (P = 0.01), and incidence of medical complications was 13.4% in the Control Group and 3.1% in the Over‐75 Group. Median postoperative hospitalization and transfusions were not statistically different.

Conclusions

Hepatic resections in over‐75‐year‐old patients are not a surgical hazard and may be carried out relatively safely as long as an accurate selection of the patient is performed. J. Surg. Oncol. 2006;93: 186–193. © 2006 Wiley‐Liss, Inc.
p27 downregulation and metallothionein overexpression in gastric cancer patients are associated with a poor survival rate
Authors: Galizia Gennaro , Ferraraccio Francesca , Lieto Eva , Orditura Michele , Castellano Paolo , Imperatore Vincenzo , La Manna Giovanni , Pinto Margherita , Ciardiello Fortunato , La Mura Anna , De Vita Ferdinando
Published: February 2006

Background and Objectives

As a significant number of curatively treated gastric cancer patients will ultimately relapse, there is an urgent need to investigate new prognostic markers for identification of high‐risk patients. In this study, we investigated the possible role of molecular markers involved in cell cycle regulation (B1 and D3 cyclins, and p27) and cell protection (metallothionein, MT) in predicting tumor behavior and clinical outcome in gastric cancer patients.

Methods

Analysis of the above indicators was performed by immunohistochemistry on 73 gastric cancer patient samples and 25 normal gastric mucosa specimens.

Results

Normal gastric mucosa cells displayed low expressions of B1 and D3 cyclins and MT, and intense p27 staining. Conversely, gastric tumor cells showed higher cyclin D3 and MT, and lower p27 expressions. B1 cyclin expressions were not different between normal and tumor tissue. p27 and MT expressions were altered in almost all cancer samples, and were strongly correlated with tumor progression. Advanced extent of the primary tumor, nodal metastasis, low p27, and high MT expressions were the best combination of variables for prediction of poor clinical outcome. Each marker predicted outcome better than staging based on tumor‐node (TNM) system. Survival and recurrence rates decreased as molecular alterations increased. Finally, molecular profile determination correctly predicted the prognosis in patients with same TNM stage.

Conclusions

p27 and MT expressions strongly correlated with clinical outcome allowing to identify an unfavorable group of patients that may benefit from tailored treatments. The role of B1 and D3 cyclins in gastric cancer remains to be elucidated. J. Surg. Oncol. 2006;93: 241–252. © 2006 Wiley‐Liss, Inc.
Sentinel lymph node biopsy in thin melanoma patients
Authors: Hershko Dan D. , Robb Bruce W. , Lowy Andrew M. , Ahmad Syed A. , Ramadas Go H. , Soldano Debbie A. , Sussman Jeffrey J.
Published: February 2006

Background

We sought to determine the incidence of positive sentinel lymph nodes in thin melanoma (≤1.0 mm) patients and if subgroups could be identified with a higher risk of occult nodal disease.

Methods

Patients with ≤1.0 mm lesions treated between 1997 and 2003 were reviewed. Sentinel nodes underwent microscopic analysis including step sectioning and immunohistochemical examination. Some nodes underwent reverse transcriptase‐polymerase chain reaction (RT‐PCR) evaluation for melanoma markers.

Results

Sixty‐four of 107 thin melanoma patients underwent sentinel node biopsy (SNB). Mapped patients were more likely to have Clark ≥ III and thicker lesions (mean 0.77 mm vs. 0.47mm), but were not different in regards to age, sex, or lesion location. Eight percent and 58% of sentinel nodes were positive by routine histology and RT‐PCR, respectively. Among mapped patients, younger age was the only significant prognostic factor for node positivity. With a median follow‐up of 18 months among all patients, one regional recurrence (at 2 years) has been identified.

Conclusions

Given the low morbidity of sentinel lymph node biopsy, this procedure should be discussed with selected thin melanoma patients to detect microscopic disease, however PCR positivity by our methods is too commonly seen to be clinically significant in thin melanoma patients and requires additional study. J. Surg. Oncol. 2006;93: 279–285. © 2006 Wiley‐Liss, Inc.
Prognostic factors of myxofibrosarcomas: Implications of margin status, tumor necrosis, and mitotic rate on survival
Authors: Lin Ching‐Nan , Chou Shin‐Cheng , Li Chien‐Feng , Tsai Kun‐Bow , Chen Wen‐Chung , Hsiung Ching‐Yeh , Yen Cheng‐Fang , Huang Hsuan‐Ying
Published: February 2006

Background

Myxofibrosarcomas (MFS) are characterized by tumor progression with increased metastases after local recurrences (LR). Few series had appropriately addressed what parameters independently affect prognosis.

Methods

Seventy primary localized MFS were analyzed for local recurrence‐free survival (LRFS), metastasis‐free survival (MeFS), and disease‐specific survival (DSS). Follow‐up was obtained in 61 cases.

Results

Thirty‐eight males and 32 females had primary tumors ranging from 1.5 to 24 cm. Thirty and 40 tumors were superficial and deep, respectively, with 26 cases (38%) having positive margins. The 5‐year LRFS‐, MeFS‐, and DSS‐rates were 30%, 60%, and 73%. Positive margins (P = 0.0003) were the only inferior LRFS predictor. High grade (FNCLCC 2 and 3) was a negative factor of both MeFS (P = 0.0078) and DSS (P = 0.0174), and high stage (AJCC stage 3) was predictive of MeFS (P = 0.0470). However, both grading and staging were not prognostically independent. In multivariate analyses, mitoses ≥20/10 HPF (P = 0.0009, RR = 9.71) and positive margins (P = 0.0203, RR = 4.27) were independent adverse DSS predictor. However, tumor necrosis ≥10% (P = 0.0092, RR = 3.91) independently correlated with worse MeFS, together with mitoses ≥20/10 HPF (P = 0.0176, RR = 3.80) and positive margins (P = 0.0121, RR = 3.41).

Conclusions

Margin status and histologic property both affect the prognosis of MFS. The former correlates with improved LRFS and translates into final survival benefits. J. Surg. Oncol. 2006;93:294–303. © 2006 Wiley‐Liss, Inc.
Double‐barreled wet colostomy is a safe option for simultaneous urinary and fecal diversion. Analysis of 56 procedures from a single institution
Authors: Guimaraes Gustavo C. , Ferreira Fabio O. , Rossi Benedito M. , Aguiar Samuel , Zequi Stenio C. , Bachega Wilson , Nakagawa Wilson T. , Fonseca Francisco P. , Sarkis Alvaro S. , Lopes Ademar
Published: February 2006

Background and Objectives

Wide pelvic tumors need urinary and fecal diversion. We set out to assess the efficacy of the double‐barreled wet colostomy (DBWC) in patients undergoing simultaneous double diversion.

Material and Methods

We reviewed 56 consecutive patients submitted to surgery, divided into two groups: (1) total pelvic exenteration plus DBWC (n = 26); (2) DBWC without simultaneous pelvic resection (n = 30). Pelvic tumor recurrences accounted for most patients (n = 53), whereas the remaining three patients suffered from actinic pelvic complications.

Results

Surgical morbidity and mortality rates were 53.8% (14/26) and 11.5% (3/26) in Group 1, and 43.5% (13/30) and 3.3% (1/30) in Group 2, respectively. Only 2 patients out of 51 (3.9%) developed late postoperative urinary tract infection. Regression of the hydronephrosis was observed in 28 out of 33 assessable patients. Median survival in Groups 1 and 2 was 8.36 and 4.14 months, respectively. In the subgroup of patients submitted to curative surgery (n = 24), actuarial cancer‐specific survival rate in 2 years was 58.78%.

Conclusion

DBWC is a safe and efficient alternative for simultaneous urinary and fecal diversion, with low morbidity and mortality rates, improvement of renal insufficiency, and low risk of postoperative urinary tract infection. J. Surg. Oncol. 2006;93: 206–211. © 2006 Wiley‐Liss, Inc.
Bladder recurrence of upper urinary tract cancer after laparoscopic surgery
Authors: Kume Haruki , Teramoto Shinji , Tomita Kyoichi , Nishimatsu Hiroaki , Takahashi Satoru , Takeuchi Takumi , Ota Nobutaka , Kitamura Tadaichi
Published: February 2006

Purpose

We reviewed our cases to determine whether laparoscopic nephroureterectomy is a risk factor for the bladder recurrence.

Materials and Methods

From 1996 to 2003, 65 nephroureterectomies were performed: 47 by open and 18 by laparoscopic surgery. In 43 (28 by open, 15 by laparoscopic surgery), bladder cancer was not observed at the time of the operation. Two laparoscopic operations were converted to open surgery because of technical problems. The other 13 with laparoscopic and 28 with open surgery were enrolled into this study.

Results

Significantly higher recurrence rate was observed in laparoscopic cases (69.2%) than that in open cases (35.7%, P = 0.0484) by log rank test. However, the operation time required in laparoscopic surgery (371.5 ± 90.8 min) was significantly longer than that in the open surgery (229.9 ± 46.6 min, P < 0.0001). In multivariate analysis (Cox proportional hazards model), only the longer operation time (>250 min) was a significant variable (P = 0.0305), and laparoscopic surgery in itself was not a significant risk factor (P = 0.5011).

Conclusions

Although frequent bladder recurrence was observed in laparoscopic cases, the most important risk factor was the longer operation time. Technical improvements including shortening of operation time and earlier ureteral ligation may decrease the bladder recurrence. J. Surg. Oncol. 2006;93: 318–322. © 2006 Wiley‐Liss, Inc.
Complications following pulsed dye laser treatment of superficial hemangiomas
Authors: Witman Patricia M. , Wagner Annette M. , Scherer Kathrin , Waner Milton , Frieden Ilona J.
Published: February 2006

Background and Objective

Pulsed dye laser (PDL) has been reported to be safe and effective in the management of superficial hemangiomas of infancy. We report 12 patients with hemangiomas with complications following PDL.

Study Design/Materials and Methods

Records of patients with hemangiomas and a known adverse outcome following PDL were reviewed.

Results

All were treated early (age range: 5 days to 4 months), and all hemangiomas were facial with a superficial component. Eleven were treated with a 585 nm wavelength, fluence range of 4.7–7 J/cm2, without dynamic cooling. One patient received 7–12 J/cm2 utilizing a 595 nm wavelength with dynamic cooling. In eight cases, treatment led to severe ulceration with subsequent pain, scarring, and in one instance, life‐threatening hemorrhage. In four, permanent atrophic scarring was noted without ulceration.

Conclusions

PDL treatment of superficial hemangiomas may rarely lead to significant complications including atrophic scarring and severe ulceration. Lasers Surg. Med. 38:116–123, 2006. © 2006 Wiley‐Liss, Inc.