bluuebunny/crossref_metadata_2025 huggingface dataset:
SOCS3 in T and NKT Cells Negatively Regulates Cytokine Production and Ameliorates ConA-Induced Hepatitis
Authors: Nakaya Mako , Hashimoto Masayuki , Nakagawa Ryusuke , Wakabayashi Yu , Ishizaki Takuma , Takada Ichiro , Komai Kyoko , Yoshida Hiroki , Yoshimura Akihiko
Published: November 2009

Suppressor of cytokine signaling 3 (SOCS3), a negative-feedback molecule for cytokine signaling, has been implicated in protection against liver injury. Previous studies have shown that overexpression of SOCS3 in the liver by adenovirus or membrane permeable recombinant protein protected the liver from various injuries. However it remained uncertain in which type of cells SOCS3 suppresses liver injury. In this study, we demonstrated that forced expression of SOCS3 in T and NKT cells suppressed ConA-induced hepatitis using T and NKT cell-specific SOCS3 transgenic (Lck-SOCS3 Tg) mice. IFN-γ and IL-4 production was reduced in Lck-SOCS3 Tg mice as well as splenocytes treated with ConA. IFN-γ and IL-4 levels were also reduced in Lck-SOCS3 Tg mice administrated with α-galactosylceramide, suggesting that SOCS3 in NKT cells has suppressive function. Sustained expression of SOCS3 in an NKT cell line also resulted in reduced expression of various cytokines and transcription factors. In contrast, T and NKT cell-specific SOCS3 conditional knockout (Lck-SOCS3 cKO) mice were hypersensitive to ConA-mediated hepatitis. Isolated SOCS3-deficient NKT cells produced higher levels of IFN-γ and IL-4. These data indicate that SOCS3 plays a negative regulatory role in NKT cell activation and that forced expression of SOCS3 in NKT cells is effective in preventing hepatitis.
TLR2 Promotes Th2/Th17 Responses via TLR4 and TLR7/8 by Abrogating the Type I IFN Amplification Loop
Authors: Wenink Mark H. , Santegoets Kim C. M. , Broen Jacobus C. A. , van Bon Lenny , Abdollahi-Roodsaz Shahla , Popa Calin , Huijbens Richard , Remijn Thijs , Lubberts Erik , van Riel Piet L. C. M. , van den Berg Wim B. , Radstake Timothy R. D. J.
Published: November 2009

TLR2 plays an important role in the removal of Gram-positive bacteria; contrastingly, it also appears to have important protective effects against unrestrained inflammation and subsequent organ injury during infection and autoimmunity. We hypothesized that TLR2 tunes the phenotype of dendritic cells (DCs) activated through other TLRs, thereby fulfilling a crucial role in the modulation of the immune response. TLR2 potently inhibited TLR4- and TLR7/8-induced cytokine production by human DCs. The inhibitory effect of TLR2 on the release of TNF-α but not of IL-12p70 was mediated by PI3K. TLR2 inhibits the production of IL-12p70 by dampening the type 1 IFN amplification loop. When DCs were triggered with the potent synergistic combination of LPS (TLR4) and R848 (TLR7/8) in conjunction with a TLR2 ligand, a clear shift to more Th2- and Th17-prone responses in the naive and memory T cell subpopulations was observed. This shift in T cell responses was inherent to the inability of TLR2-stimulated DCs to produce IL-12p70 and was dependent on the production of IL-1 and IL-6.
Prostacyclin Inhibits IFN-γ-Stimulated Cytokine Expression by Reduced Recruitment of CBP/p300 to STAT1 in a SOCS-1-Independent Manner
Authors: Strassheim Derek , Riddle Suzzette R. , Burke Danielle L. , Geraci Mark W. , Stenmark Kurt R.
Published: November 2009

Increasing evidence indicates that pulmonary arterial hypertension is a vascular inflammatory disease. Prostacyclin (PGI2) is widely used to treat pulmonary arterial hypertension and is believed to benefit patients largely through vasodilatory effects. PGI2 is also increasingly believed to have anti-inflammatory effects, including decreasing leukocyte cytokine production, yet few mechanistic details exist to explain how these effects are mediated at the transcriptional level. Because activated monocytes are critical sources of MCP-1 and other cytokines in cardiovascular inflammation, we examined the effects of iloprost on IFN-γ- and IL-6-stimulated cytokine production in human monocytes. We found that iloprost inhibited IFN-γ- and IL-6-induced MCP-1, IL-8, RANTES, and TNF-α production in monocytes, indicating wide-ranging anti-inflammatory action. We found that activation of STAT1 was critical for IFN-γ-induced MCP-1 production and demonstrated that iloprost inhibited STAT1 activation by several actions as follows: 1) iloprost inhibited the phosphorylation of STAT1-S727 in the transactivation domain, thereby reducing recruitment of the histone acetylase and coactivator CBP/p300 to STAT1; 2) iloprost selectively inhibited activation of JAK2 but not JAK1, both responsible for activation of STAT1 via phosphorylation of STAT1-Y701, resulting in reduced nuclear recruitment and activation of STAT1; and 3) SOCS-1, which normally terminates IFN-γ-signaling, was not involved in iloprost-mediated inhibition of STAT1, indicating divergence from the classical pathway for terminating IFN-γ-signaling. We conclude that PGI2 exerts anti-inflammatory action by inhibiting STAT1-induced cytokine production, in part by targeting the transactivation domain-induced recruitment of the histone acetylase CBP/p300.
Systemic Increase in the Ratio between Foxp3+ and IL-17-Producing CD4+ T Cells in Healthy Pregnancy but Not in Preeclampsia
Authors: Santner-Nanan Brigitte , Peek Michael John , Khanam Roma , Richarts Luise , Zhu Erhua , Fazekas de St Groth Barbara , Nanan Ralph
Published: November 2009

Preeclampsia is the leading cause of morbidity and mortality in pregnancy. Although the etiology of preeclampsia is still unclear, it is believed to involve rejection of the fetus, possibly due to an imbalance between regulatory (Treg) and effector T cells. To test this, we compared the frequencies of circulating CD4+ T cells expressing Foxp3, IFN-γ, IL-10, or IL-17 at the end of the third trimester of healthy and preeclamptic pregnancies. The size of the Treg cell compartment, defined by the frequency of CD4+CD25high, CD4+CD127lowCD25+, and CD4+Foxp3+ cells was significantly higher in normal compared with preeclamptic pregnancies. CD4+CD25high and CD4+CD127lowCD25+ populations in preeclampsia were not significantly different from those in nonpregnant controls, whereas CD4+Foxp3+ cells numbersre slightly lower in preeclampsia. The suppressive activity of ex vivo-sorted CD4+CD127lowCD25+ Treg cells was not significantly different between the three study groups. The percentage of CD4+IL-17-producing T cells decreased significantly in healthy compared with preeclamptic pregnancies and nonpregnant controls, whereas CD4+IL-10- and CD4+IFN-γ-producing cells remained unchanged. Consequently, the ratio of Foxp3+ Treg to IL-17-expressing CD4+ T cells was significantly increased in healthy but not in preeclamptic pregnancies. Thus, preeclampsia is associated with the absence of normal systemic skewing away from IL-17 production toward Foxp3+ expression. Finally, preeclamptic women had significantly higher levels of soluble endoglin, an inhibitor of TGF-β receptor signaling, which may bias toward IL-17 production. These results suggest that homeostasis between regulatory and proinflammatory CD4+ T cells might be pivotal for the semiallogeneic fetus to be tolerated within the maternal environment.
Ectopic T-bet Expression Licenses Dendritic Cells for IL-12-Independent Priming of Type 1 T Cells In Vitro
Authors: Lipscomb Michael W. , Chen Lu , Taylor Jennifer L. , Goldbach Christina , Watkins Simon C. , Kalinski Pawel , Butterfield Lisa H. , Wesa Amy K. , Storkus Walter J.
Published: November 2009

T-bet (TBX21) is a transcription factor required for the optimal development of type 1 immune responses. Although initially characterized for its intrinsic role in T cell functional polarization, endogenous T-bet may also be critical to the licensing of type 1-biasing APCs. Here, we investigated whether human dendritic cells (DC) genetically engineered to express high levels of T-bet (i.e., DC.Tbet) promote superior type 1 T cell responses in vitro. We observed that DC.Tbet were selective activators of type 1 effector T cells developed from the naive pool of responder cells, whereas DC.Tbet and control DC promoted type 1 responses equitably from the memory pool of responder cells. Naive T cells primed by (staphylococcal enterotoxin B or tumor-associated protein-loaded) DC.Tbet exhibited an enhancement in type 1- and a concomitant reduction in Th2- and regulatory T cell-associated phenotype/function. Surprisingly, DC.Tbets were impaired in their production of IL-12 family member cytokines (IL-12p70, IL-23, and IL-27) when compared with control DC, and the capacity of DC.Tbet to preferentially prime type 1 T cell responses was only minimally inhibited by cytokine (IL-12p70, IL-23, IFN-γ) neutralization or receptor (IL-12Rβ2, IL-27R) blockade during T cell priming. The results of transwell assays suggested the DC.Tbet-mediated effects are predominantly the result of direct DC-T cell contact or their close proximity, thereby implicating a novel, IL-12-independent mechanism by which DC.Tbets promote improved type 1 functional polarization from naive T cell responders. Given their superior type 1 polarizing capacity, DC.Tbet may be suitable for use in vaccines designed to prevent/treat cancer or infectious disease.
Impaired NK Cytolytic Activity and Enhanced Tumor Growth in NK Lytic-Associated Molecule-Deficient Mice
Authors: Hoover Richard G. , Gullickson Gail , Kornbluth Jacki
Published: November 2009

NK lytic-associated molecule (NKLAM) is a protein involved in the cytolytic function of NK cells. It is weakly expressed in resting NK cells but upon target cell stimulation or after incubation with cytokines that enhance NK killing, NKLAM mRNA levels increase and protein is synthesized and is targeted to cytoplasmic granule membranes. We have previously shown that NKLAM plays a role in perforin/granzyme-mediated cytolysis in vitro. To further investigate the function of NKLAM in NK cell-mediated cytotoxicity, we generated, by gene targeting, NKLAM-deficient mice. These mice have normal numbers of NK cells and other lymphoid populations in the spleen. They also have no alterations in NK maturation or NK receptor repertoire. NK cells from NKLAM-deficient and WT mice have comparable amounts of perforin, granzyme B, and lysosomal membrane-associated protein 1 (CD107a) in their cytotoxic granules and comparable levels of granule exocytosis are induced by PMA and calcium ionophore A23187. However, NKLAM-deficient NK cells display significantly less NK cytotoxic activity in vitro than WT NK cells. They also secrete less IFN-γ upon target cell stimulation, In addition, NKLAM-deficient mice exhibit greater numbers of pulmonary metastases after i.v. injection with B16 melanoma cells. These studies indicate that NKLAM-deficient mice have diminished capacity to control tumor metastases and support the role for NKLAM in NK function both in vitro and in vivo.
Chimeric NKG2D Expressing T Cells Eliminate Immunosuppression and Activate Immunity within the Ovarian Tumor Microenvironment
Authors: Barber Amorette , Rynda Agnieszka , Sentman Charles L.
Published: November 2009

Adoptive transfer of T cells expressing chimeric NKG2D (chNKG2D) receptors, a fusion of NKG2D and CD3ζ, can lead to long-term, tumor-free survival in a murine model of ovarian cancer. To determine the mechanisms of chNKG2D T cell antitumor efficacy, we analyzed how chNKG2D T cells altered the tumor microenvironment, including the tumor-infiltrating leukocyte populations. chNKG2D T cell treatment of mice bearing ID8 tumor cells increased the number and activation of NK cells and increased the activation of host CD8+ T cells within the tumor. Foxp3+ regulatory T cells at the tumor site decreased more than 300-fold after chNKG2D T cell treatment. Tumor-associated regulatory T cells expressed cell surface NKG2D ligands and were killed by chNKG2D T cells in a perforin-dependent manner. chNKG2D T cells also altered the function of myeloid cells at the tumor site, changing these cells from being immunosuppressive to enhancing T cell responses. Cells isolated from the tumor produced elevated amounts of IFN-γ, NO, and other proinflammatory cytokines after chNKG2D T cell treatment. ChNKG2D T cells required perforin, IFN-γ, and GM-CSF to induce a full response at the tumor site. In addition, transfer of chNKG2D T cells into mice bearing tumors that were established for 5 weeks led to long-term survival of the mice. Thus, chNKG2D T cells altered the ovarian tumor microenvironment to eliminate immunosuppressive cells and induce infiltration and activation of antitumor immune cells and production of inflammatory cytokines. This induction of an immune response likely contributes to chNKG2D T cells’ ability to eliminate established tumors.
MHC Drives TCR Repertoire Shaping, but not Maturation, in Recent Thymic Emigrants
Authors: Houston Evan G. , Fink Pamela J.
Published: November 2009

After developing in the thymus, recent thymic emigrants (RTEs) enter the lymphoid periphery and undergo a maturation process as they transition into the mature naive (MN) T cell compartment. This maturation presumably shapes RTEs into a pool of T cells best fit to function robustly in the periphery without causing autoimmunity; however, the mechanism and consequences of this maturation process remain unknown. Using a transgenic mouse system that specifically labels RTEs, we tested the influence of MHC molecules, key drivers of intrathymic T cell selection and naive peripheral T cell homeostasis, in shaping the RTE pool in the lymphoid periphery. We found that the TCRs expressed by RTEs are skewed to longer CDR3 regions compared with those of MN T cells, suggesting that MHC does streamline the TCR repertoire of T cells as they transition from the RTE to the MN T cell stage. This conclusion is borne out in studies in which the representation of individual TCRs was followed as a function of time since thymic egress. Surprisingly, we found that MHC is dispensable for the phenotypic and functional maturation of RTEs.
Dynamic Regulation of Notch 1 and Notch 2 Surface Expression during T Cell Development and Activation Revealed by Novel Monoclonal Antibodies
Authors: Fiorini Emma , Merck Estelle , Wilson Anne , Ferrero Isabel , Jiang Wei , Koch Ute , Auderset Floriane , Laurenti Elisa , Tacchini-Cottier Fabienne , Pierres Michel , Radtke Freddy , Luther Sanjiv A. , MacDonald H. Robson
Published: November 2009

It is well established that Notch signaling plays a critical role at multiple stages of T cell development and activation. However, detailed analysis of the cellular and molecular events associated with Notch signaling in T cells is hampered by the lack of reagents that can unambiguously measure cell surface Notch receptor expression. Using novel rat mAbs directed against the extracellular domains of Notch1 and Notch2, we find that Notch1 is already highly expressed on common lymphoid precursors in the bone marrow and remains at high levels during intrathymic maturation of CD4−CD8− thymocytes. Notch1 is progressively down-regulated at the CD4+CD8+ and mature CD4+ or CD8+ thymic stages and is expressed at low levels on peripheral T cells. Immunofluorescence staining of thymus cryosections further revealed a localization of Notch1+CD25− cells adjacent to the thymus capsule. Notch1 was up-regulated on peripheral T cells following activation in vitro with anti-CD3 mAbs or infection in vivo with lymphocytic chorio-meningitis virus or Leishmania major. In contrast to Notch1, Notch2 was expressed at intermediate levels on common lymphoid precursors and CD117+ early intrathymic subsets, but disappeared completely at subsequent stages of T cell development. However, transient up-regulation of Notch2 was also observed on peripheral T cells following anti-CD3 stimulation. Collectively our novel mAbs reveal a dynamic regulation of Notch1 and Notch2 surface expression during T cell development and activation. Furthermore they provide an important resource for future analysis of Notch receptors in various tissues including the hematopoietic system.
SLAT/Def6 Plays a Critical Role in the Development of Th17 Cell-Mediated Experimental Autoimmune Encephalomyelitis
Authors: Canonigo-Balancio Ann J. , Fos Camille , Prod'homme Thomas , Bécart Stéphane , Altman Amnon
Published: November 2009

SWAP-70-like adapter of T cells (SLAT; also known as Def6) is a novel guanine nucleotide exchange factor for Rho GTPases that has been previously shown to play a role in CD4+ T cell activation and Th1/Th2 differentiation. However, the role of SLAT/Def6 in autoimmunity and its associated Th1- and Th17-specific responses has not yet been clearly elucidated. We used a prototypical and pathologically relevant Th1/Th17-mediated autoimmune model, that is, experimental autoimmune encephalomyelitis, to assess the role of SLAT/Def6 in autoantigen-specific T cell response. We found that T cell-expressed SLAT/Def6 was critical for experimental autoimmune encephalomyelitis development and pathogenesis, as evidenced by the resistance of Def6-deficient (Def6−/−) mice to clinical signs of the disease associated with a lack of CNS inflammation and demyelination in myelin oligodendrocyte glycoprotein-immunized Def6−/− mice. Moreover, Def6 deficiency resulted in a severely diminished myelin oligodendrocyte glycoprotein-specific CD4+ T cell proliferation as well as a defect in IFN-γ and IL-17 production in secondary lymphoid organs and the CNS. Lastly, Def6−/− CD4+ T cells were grossly deficient in their ability to differentiate into Th17 cells both in vitro and in vivo in a T cell-intrinsic manner. Therefore, our study establishes T cell-expressed SLAT/Def6 as a pivotal positive regulator of Th17 inflammatory responses and, thus, essential in controlling autoimmune and inflammatory diseases.
Thermal degradation kinetics of poly(O,O‐diethyl‐O‐allylthiophosphate‐co‐acrylonitrile) in nitrogen
Authors: Ren Yuanlin , Cheng Bowen , Jiang Aibing , Lu Youcai , Xu Ling
Published: November 2009

The nonisothermal degradation kinetics of the copolymer poly(O,O‐diethyl‐O‐allylthiophosphate‐co‐acrylonitrile), which was synthesized with O,O‐diethyl‐O‐allylthiophosphate and acrylonitrile, were studied by thermogravimetry/derivative thermogravimetry techniques. The kinetic parameters, including the activation energy and the pre‐exponential factor of the copolymer degradation process, were calculated by the Kissinger and Flynn–Wall–Ozawa methods. The thermal degradation mechanism of the copolymer was also studied with the Satava–Sestak method. The results show that the activation energies were 138.17 kJ/mol with the Kissinger method and 141.63 kJ/mol with the Flynn–Wall–Ozawa method. The degradation of the copolymer followed a kinetic model of a phase boundary reaction and the kinetic equation could be expressed as G(α) = 1 − (1 − α)4 [where G(α) is the integral function of conversion and α is the extent of conversion of the reactant decomposed at time t]. The reaction order was 4. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Polysulfone‐azo composite membrane: New preparative approach, importance in bactericidal and biofilm inhibition activities
Authors: Yogesh  , Haldar S. , Paul P. , Bhattacharya A.
Published: November 2009

The study in particular relates to a process for modifying surface of polymeric membrane and their biocidal activities. The modification process is based on absorption of 1, 3, phenylene diamine on the asymmetric polysulfone membrane and its diazo reaction. The azo compound (Bismarck brown) is characterized by LC‐mass, uv–vis spectra. The incorporation of azo compound into polysulfone asymmetric membrane is proved by ATR‐FTIR, SEM studies. The decrease in contact angle for modified surface proves the development of hydrophilic character. The modified membrane shows higher biocidal activity (for marine bacteria Vibrio sp.) compared to the virgin polysulfone membrane. The biofilm formation is inhibited for the modified membrane compared to virgin Polysulfone membrane. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Prediction of Hildebrand solubility parameters of acrylate and methacrylate monomers and their mixtures by molecular simulation
Authors: Lewin John L. , Maerzke Katie A. , Schultz Nathan E. , Ross Richard B. , Siepmann J. Ilja
Published: November 2009

Hildebrand solubility parameters are predicted from molecular simulations using the transferable potentials for phase equilibrium‐united atom (TraPPE‐UA) and Dreiding force fields for the n‐alkyl acrylate and methacrylate esters (n ≤ 10), as well as the 2‐ethylhexyl acrylate, 2‐hydroxyethyl acrylate, isooctyl esters of acrylic acid, and the 2‐hydroxyethyl ester of methacrylic acid. The TraPPE‐UA force field yields very accurate solubility parameters (with a mean unsigned percent error of 2% or 0.2 Hildebrand units), whereas the Dreiding force field overpredicts the solubility parameter in every case examined. Correlations based on the normal boiling point or the refractive index do not yield satisfactory results for this monomer set with the former overestimating the magnitude and the latter yielding the incorrect sign for the decrease in the solubility parameter with chain length. Simulations with the TraPPE‐UA force field yield solubility parameters for binary mixtures of methyl methacrylate with 2‐ethylhexyl or isooctyl acrylate, which are very well described by a linear interpolation using the pure compound cohesive energies and molar volumes, whereas those for mixtures with 2‐hydroxyethyl acrylate or methacrylate small positive deviations due to structural microheterogeneity. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Digital artifacts as quasi‐objects: Qualification, mediation, and materiality
Authors: Ekbia Hamid R.
Published: November 2009

Digital artifacts have novel properties that largely derive from the processes that mediate their creation, and that can be best understood by a close examination of such processes. This paper introduces the concept of “quasi‐object” to characterize these objects and elucidate the activities that comprise their mediations. A case study of “bugs” is analyzed to illustrate exemplary activities of justification, qualification, and binding in the process of bug fixing in Free/Open Source Software development. The findings of the case study lead to broader reflections on the character of digital artifacts in general. The relationship of “quasi‐object” to other similar concepts are explored.
Indexing and searching strategies for the Russian language
Authors: Dolamic Ljiljana , Savoy Jacques
Published: November 2009

This paper describes and evaluates various stemming and indexing strategies for the Russian language. We design and evaluate two stemming approaches, a light and a more aggressive one, and compare these stemmers to the Snowball stemmer, to no stemming, and also to a language‐independent approach (n‐gram). To evaluate the suggested stemming strategies we apply various probabilistic information retrieval (IR) models, including the Okapi, the Divergence from Randomness (DFR), a statistical language model (LM), as well as two vector‐space approaches, namely, the classical tf idf scheme and the dtu‐dtn model. We find that the vector‐space dtu‐dtn and the DFR models tend to result in better retrieval effectiveness than the Okapi, LM, or tf idf models, while only the latter two IR approaches result in statistically significant performance differences. Ignoring stemming generally reduces the MAP by more than 50%, and these differences are always significant. When applying an n‐gram approach, performance differences are usually lower than an approach involving stemming. Finally, our light stemmer tends to perform best, although performance differences between the light, aggressive, and Snowball stemmers are not statistically significant.
Nationwide study of early outcomes after incisional hernia repair
Authors: Bisgaard T , Kehlet H , Bay-Nielsen M B , Iversen M G , Wara P , Rosenberg J , Friis-Andersen H F , Jorgensen L N
Published: November 2009

Background

There are no nationwide studies on early outcomes after incisional hernia repair.

Methods

This study included all patients aged 18 years or more who had surgery for incisional hernia in Denmark between 1 January 2005 and 31 December 2006, and analysed clinical outcomes within 30 days of surgery. Patients having acute operations and those whose hernia repair was secondary to other procedures were excluded.

Results

Of a total of 2896 incisional hernia repairs (1872 open, 1024 laparoscopic), 2754 (95·1 per cent) were for primary hernia and 142 (4·9 per cent) for recurrence. The median hospital stay was 1 (range 0–88) day (open, 1 day; laparoscopic, 2 days); 10·0 per cent stayed for more than 6 days. Some 11·2 per cent of patients were readmitted (open, 10·1 per cent; laparoscopic, 13·1 per cent). Major complications were observed in 3·5 per cent (open, 2·8 per cent; laparoscopic, 4·8 per cent) with a total morbidity rate of 10·7 per cent (open, 10·1 per cent; laparoscopic, 11·8 per cent). The mortality rate was 0·4 per cent (open, 0·2 per cent; laparoscopic, 0·7 per cent). Morbidity and mortality were not related to surgical volume.

Conclusion

Outcomes after incisional hernia repair seem unsatisfactory.
Endoscopic lumbar sympathectomy for plantar hyperhidrosis
Authors: Rieger R , Pedevilla S , Pöchlauer S
Published: November 2009

Background

The aim of this study was to evaluate the results of endoscopic lumbar sympathectomy for plantar hyperhidrosis.

Methods

A total of 178 endoscopic resections of the lower sympathetic lumbar trunk were carried out in 90 patients (59 men, 31 women) with severe plantar hyperhidrosis. The clinical results, including morbidity and satisfaction rates, were evaluated. Follow-up examination was carried out for all patients after a mean follow-up of 24 (range 3–45) months.

Results

All procedures were carried out endoscopically. There were no deaths and only three patients had a postoperative complication. All patients had evidence of postoperative sympathetic denervation of the feet. In 87 patients (97 per cent) hyperhidrosis was eliminated, but in three (3 per cent) it recurred. Compensatory sweating occurred in 40 patients (44 per cent), postsympathectomy neuralgia in 38 (42 per cent) and one man suffered temporary loss of ejaculation. A total of 86 patients (96 per cent) were very, or partly, satisfied with the result, and 83 (92 per cent) would have the procedure repeated if required.

Conclusion

Endoscopic lumbar sympathectomy was a safe and effective option for patients with severe plantar hyperhidrosis.
PTQ™ anal implants for the treatment of faecal incontinence
Authors: Bartlett L , Ho Y-H
Published: November 2009

Background

In North Queensland demand for conservative faecal incontinence treatments outweighs supply. Injectable bulking agents offer a safe and effective treatment for patients with internal anal sphincter (IAS) dysfunction.

Methods

Information, including age and sex, baseline incontinence score, quality of life, resting and squeeze pressures, was collected for 74 patients (37 men) who received intersphincteric PTQ™ injections. Postimplant satisfaction was assessed at 6-week review. Incontinence scores and satisfaction ratings were determined annually.

Results

At a median follow-up of 28 months, 52 patients (70 per cent) with IAS dysfunction who received PTQ™ anal implants as a treatment for faecal incontinence were continent and extremely satisfied with the result. The incontinence score in participants who remained incontinent was reduced significantly from 12 of 20 before implant to 3·5 of 20 at follow-up (P < 0·001). Migration rates improved with experience. The poorest results occurred in women with pudendal neuropathy, or patients who had previously received biofeedback treatment.

Conclusion

Implanted PTQ™ provides an effective solution to faecal incontinence in the short and mid term for patients with IAS dysfunction.
Angiogenesis, vascular endothelial growth factor and its receptors in human surgical wounds
Authors: Kumar I , Staton C A , Cross S S , Reed M W R , Brown N J
Published: November 2009

Background

Angiogenesis plays an essential role in tissue repair. Vascular endothelial growth factor (VEGF) mediates angiogenesis through receptor kinases VEGF-R1 and VEGF-R2, and co-receptors, neuropilins Np1 and Np2. This study examined the spatial and temporal expression of these factors in relation to angiogenesis in surgical wounds.

Methods

Scar biopsies were obtained from patients between 3 days and 2 years after surgery. Normal skin control biopsies were taken during surgery. Microvessel density (MVD) was quantified using a Chalkley grid. VEGF, VEGF-R1, VEGF-R2, Np1 and Np2 endothelial expression was determined by immunohistochemistry, and correlated with MVD and scar age.

Results

Cumulative MVD was significantly greater in scars than controls (P = 0·011), and was related to scar age (P = 0·007). Expression of VEGF, VEGF-R2, Np1 and Np2 was increased significantly in all scars and correlated with MVD. In contrast, scar VEGF-R1 expression was decreased, and correlated with increased VEGF and VEGF-R2.

Conclusion

Levels of VEGF, VEGF-R2, Np1 and Np2 are increased, whereas VEGF-R1 expression is decreased in angiogenesis, suggesting a role for VEGF–receptor complexes in early wound healing. This altered protein expression and increased presence of vessels is prolonged, suggesting that structural remodelling continues for at least 2 years after surgery.
Phaeochromocytomas and sympathetic paragangliomas
Authors: Petri B-J , van Eijck C H J , de Herder W W , Wagner A , de Krijger R R
Published: November 2009

Background

About 24 per cent of phaeochromocytomas (PCCs) and sympathetic paragangliomas (sPGLs) appear in familial cancer syndromes, including multiple endocrine neoplasia type 2, von Hippel–Lindau disease, neurofibromatosis type 1 and PCC–paraganglioma syndrome. Identification of these syndromes is of prime importance for patients and their relatives. Surgical resection is the treatment of choice for both PCC and sPGL, but controversy exists about the management of patients with bilateral or multiple tumours.

Methods

Relevant medical literature from PubMed, Ovid and Embase websites until 2009 was reviewed for articles on PCC, sPGL, hereditary syndromes and their treatment.

Discussion

Genetic testing for these syndromes should become routine clinical practice for those with PCC or sPGL. Patients should be referred to a clinical geneticist. Patients and family members with proven mutations should be entered into a standardized screening protocol. The preferred treatment of PCC and PGL is surgical resection; to avoid the lifelong consequences of bilateral adrenalectomy, cortex-sparing adrenalectomy is the treatment of choice.
Cell culture monitoring via an auto‐sampler and an integrated multi‐functional off‐line analyzer
Authors: Derfus Gayle E. , Abramzon Daniel , Tung Meg , Chang David , Kiss Robert , Amanullah Ashraf
Published: November 2009

Mammalian cell‐based bioprocesses are used extensively for production of therapeutic proteins. Off‐line monitoring of such cultivations via manual sampling is often labor‐intensive and can introduce operator‐dependent error into the process. An integrated multi‐functional off‐line analyzer, the BioProfile FLEX (NOVA Biomedical, Waltham MA) has been developed, which combines the functionality of three off‐line analyzers (a cell counter, an osmometer, and a gas/electrolyte & nutrient/metabolite bio‐profile analyzer) into one device. In addition, a novel automated sampling system has also been developed that allows the BioProfile FLEX to automatically analyze the culture conditions in as many as ten bioreactors. This is the first report on the development and function of this integrated analyzer and an auto‐sampler prototype for monitoring of mammalian cell cultures. Evaluation of the BioProfile FLEX was conducted in two separate laboratories and involved two BioProfile FLEX analyzers and two sets of reference analyzers (Nova BioProfile 400, Beckman‐Coulter Vi‐Cell AS, and Advanced Instruments Osmometer 3900), 13 CHO cell lines and over 20 operators. In general, BioProfile FLEX measurements were equivalent to those obtained using reference analyzers, and the auto‐sampler did not alter the samples it provided to the BioProfile FLEX. These results suggest that the system has the potential to dramatically reduce the manual labor involved in monitoring mammalian cell bioprocesses without altering the quality of the data obtained, and integration with a bioreactor control system will allow feedback control of parameters previously available only for off‐line monitoring. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Modeling of protein and phenolic compound removal from aqueous solutions by electrocoagulation
Authors: Robić Goran , Miranda Everson Alves
Published: November 2009

Electrocoagulation is a technique basically applied in water and wastewater treatment, but which has a number of potential applications in polymer, protein, drug, and vaccine delivery. In this work, we correlate the current applied between the electrodes to the removal of phenolic compounds or protein from aqueous solutions, but the principle can also be applied to other biological compounds such as plant pigments and sugars. Simple and time‐dependent models were developed based on the complex formation between these biological substances and the aluminium hydroxide gel phase. The models developed represent a good agreement with experimental data (R2 as high as 0.992). Besides construction of the models, the effect of pH on the efficiency of removal of proteins and phenolic compounds was evaluated. It was found that this parameter has significant effect on the efficiency of the electrocoagulation and the maximal removal efficiency for bovine serum albumin and phenolic compound catechin was observed at pH 8.0. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Hybrid promoters directed tBid gene expression to breast cancer cells by transcriptional targeting
Authors: Farokhimanesh Samila , Rahbarizadeh Fatemeh , Rasaee Mohammad J. , Kamali Abbas , Mashkani Baratali
Published: November 2009

Developing cancer gene therapy constructs based on transcriptional targeting of genes to cancer cells is a new and promising modality for treatment of cancer. Introducing truncated Bid (tBid), a recently known member of the Bcl‐2 family, eradicates cancer cells efficiently. For transcriptional targeting of tBid, two dual‐specificity promoters, combining cancer specific core promoters and response modules, were designed. These two core promoter modules contained cancer specific promoters of MUC1 and Survivin genes accompanied by hypoxia‐responsive elements and estrogen responsive elements (microenvironment condition of breast cancer cells) which were employed to achieve a higher and more specific level of tBid expression in breast cancer cells. Correlation of the level of tBid expression in normal and cancer cell lines with promoter activity was measured by RT‐PCR after treatment with hypoxia and estrogen. The level of tBid expression under control of new hybrid promoters was compared with its expression under control of cytomegalovirus (CMV) promoter as a control. Our data revealed that the level of tBid expression in breast cancer cells were nearly 11 times more than normal cells because of the cancer specific promoters, although tBid expression under control of CMV promoter was almost the same in normal and cancer cell lines. Increased apoptosis was detected in the transfected breast cancer cell lines by the Caspase‐3 activity assay. The application of these promoters may prove to have the advantage of tumor selective gene therapy in breast cancer cells and low‐potential toxicity for normal tissues. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Synthesis of Vitamin K1 and K1‐Chromanol by Friedel–Crafts Alkylation in Heterogeneous Catalysis
Authors: Coman Simona M. , Parvulescu Vasile I. , Wuttke Stefan , Kemnitz Erhard
Published: November 2009

The partly hydroxylated MgF2 and AlF3 materials are efficient and selective catalysts for the preparation of two important members of the vitamin K class: vitamin K1 and vitamin K1‐chromanol. The high activity in combination with high selectivity in one of the target products is due to both the acidic strength and the synergistic effect of the presence of both, optimized Brønsted and Lewis sites. Therefore, the best catalyst for a target product can be obtained through a very simple tuning of the acidic properties of the material. Moreover, the results obtained in the present study (Yvitamin K1=57.8 % and Yvitamin K1‐chromanol=71.4 %) are also very encouraging from the environmental standpoint as green elements are introduced by using solid catalysts and a biphasic solvent system.
On Wiener‐type polynomials of thorn graphs
Authors: Zhou Bo , Vukičević Damir
Published: November 2009

We derive the expressions of the ordinary, the vertex‐weighted and the doubly vertex‐weighted Wiener polynomials of a type of thorn graph, for which the number of pendant edges attached to any vertex of the underlying parent graph is a linear function of its degree. We also define variable vertex‐weighted Wiener polynomials and calculate them for the same type of thorn graphs. Copyright © 2009 John Wiley & Sons, Ltd.
Effect of CO on the Oxidative Addition of Arene CH Bonds by Cationic Rhodium Complexes
Authors: Montag Michael , Efremenko Irena , Cohen Revital , Shimon Linda J. W. , Leitus Gregory , Diskin‐Posner Yael , Ben‐David Yehoshoa , Salem Hiyam , Martin Jan M. L. , Milstein David
Published: November 2009

Sequential addition of CO molecules to cationic aryl–hydrido RhIII complexes of phosphine‐based (PCP) pincer ligands was found to lead first to CH reductive elimination and then to CH oxidative addition, thereby demonstrating a dual role of CO. DFT calculations indicate that the oxidative addition reaction is directly promoted by CO, in contrast to the commonly accepted view that CO hinders such reactions. This intriguing effect was traced to repulsive π interactions along the aryl‐Rh‐CO axis, which are augmented by the initially added CO ligand (due to antibonding interactions between occupied Rh dπ orbitals and occupied π orbitals of both CO and the arene moiety), but counteracted by the second CO ligand (due to significant π back‐donation). These repulsive interactions were themselves linked to significant weakening of the π‐acceptor character of CO in the positively charged rhodium complexes, which is concurrent with an enhanced σ‐donating capability. Replacement of the phosphine ligands by an analogous phosphinite‐based (POCOP) pincer ligand led to significant changes in reactivity, whereby addition of CO did not result in CH reductive elimination, but yielded relatively stable mono‐ and dicarbonyl aryl–hydrido POCOP–RhIII complexes. DFT calculations showed that the stability of these complexes arises from the higher electrophilicity of the POCOP ligand, relative to PCP, which leads to partial reduction of the excessive π‐electron density along the aryl‐Rh‐CO axis. Finally, comparison between the effects of CO and acetonitrile on CH oxidative addition revealed that they exhibit similar reactivity, despite their markedly different electronic properties. However, DFT calculations indicate that the two ligands operate by different mechanisms.
Alkane Activation over Acidic Zeolites: The First Step
Authors: Louis Benoit , Pereira M. Maciel , Santos Fabiana M. , Esteves Pierre M. , Sommer Jean
Published: November 2009

The heterogeneous acid‐catalyzed activation step of alkanes leading to the reaction intermediates (carbocationic or alkoxy species) was up to now the matter of a longstanding controversy. Gas chromatography and online mass spectroscopy measurements show that H2 and methane are formed over H‐zeolites, whereas HD and CH3D are formed over D‐zeolites as the primary products in the reaction with isobutane. These results indicate that σ‐bond protolysis by strong acid sites is the first step for hydrocarbon activation on these catalysts at mild temperatures (473 K), in analogy to the activation path occurring in liquid superacid media.
Tuning Hydrogen Sorption Properties of Metal–Organic Frameworks by Postsynthetic Covalent Modification
Authors: Wang Zhenqiang , Tanabe Kristine K. , Cohen Seth M.
Published: November 2009

Postsynthetic modification is presented as a means to tune the hydrogen adsorption properties of a series of metal–organic frameworks (MOFs). IRMOF‐3 (isoreticular metal–organic framework), UMCM‐1‐NH2 (University of Michigan crystalline material), and DMOF‐1‐NH2 (DABCO metal–organic framework) have been covalently modified with a series of anhydrides or isocyanates and the hydrogen sorption properties have been studied. Both the storage capacities and isosteric heats of adsorption clearly show that covalent postsynthetic modification can significantly enhance the sorption affinity of MOFs with hydrogen and in some cases increase both gravimetric and volumetric uptake of the gas as much as 40 %. The significance of the present study is illustrated by: 1) the nature of the substituents introduced by postsynthetic modification result in different effects on the binding of hydrogen; 2) the covalent postsynthetic modification approach allows for systematic modulation of hydrogen sorption properties; and 3) the ease of postsynthetic modification of MOFs allows a direct evaluation of the interplay between MOF structure, hydrogen uptake, and heat of adsorption. The findings presented herein show that postsynthetic modification is a powerful method to manipulate and better understand the gas sorption properties of MOFs.
Placebo and nocebo effects in randomized double‐blind clinical trials of agents for the therapy for fatigue in patients with advanced cancer
Authors: de la Cruz Maxine , Hui David , Parsons Henrique A. , Bruera Eduardo
Published: November 2009

BACKGROUND:

A significant response to placebo in randomized controlled trials of treatments for cancer‐related fatigue (CRF) had been reported. A retrospective study was conducted to determine the frequency and predictors of response to placebo effect and nocebo effects in patients with CRF treated in those trials.

METHODS:

The records of 105 patients who received placebo in 2 previous randomized clinical trials conducted by this group were reviewed. The proportion of patients who demonstrated clinical response to fatigue, defined as an increase in Functional Assessment of Chronic Illness Therapy‐Fatigue score of ≥7 from baseline to Day 8, and the proportion of patients with a nocebo effect, defined as those reporting >2 side effects, were determined. Baseline patient characteristics and symptoms recorded using the Edmonton Symptom Assessment Scale (ESAS) were analyzed to determine their association with placebo and nocebo effects.

RESULTS:

Fifty‐nine (56%) patients had a placebo response. Worse baseline anxiety and well‐being subscale score (univariate) and well‐being (multivariate) were significantly associated with placebo response. Commonly reported side effects were insomnia (79%), anorexia (53%), nausea (38%), and restlessness (34%). Multivariate analysis indicated that worse baseline (ESAS) sleep, appetite, and nausea were associated with increased reporting of the corresponding side effects.

CONCLUSIONS:

Greater than half of advanced cancer patients enrolled in CRF trials had a placebo response. Worse baseline physical well‐being score was associated with placebo response. Patients experiencing specific symptoms at baseline were more likely to report these as side effects of the medication. These findings should be considered in the design of future CRF trials. Cancer 2010. © 2009 American Cancer Society.
WNT5A mutations in patients with autosomal dominant Robinow syndrome
Authors: Person Anthony D. , Beiraghi Soraya , Sieben Christine M. , Hermanson Spencer , Neumann Ann N. , Robu Mara E. , Schleiffarth J. Robert , Billington Charles J. , van Bokhoven Hans , Hoogeboom Jeannette M. , Mazzeu Juliana F. , Petryk Anna , Schimmenti Lisa A. , Brunner Han G. , Ekker Stephen C. , Lohr Jamie L.
Published: November 2009

Robinow syndrome is a skeletal dysplasia with both autosomal dominant and autosomal recessive inheritance patterns. It is characterized by short stature, limb shortening, genital hypoplasia, and craniofacial abnormalities. The etiology of dominant Robinow syndrome is unknown; however, the phenotypically more severe autosomal recessive form of Robinow syndrome has been associated with mutations in the orphan tyrosine kinase receptor, ROR2, which has recently been identified as a putative WNT5A receptor. Here, we show that two different missense mutations in WNT5A, which result in amino acid substitutions of highly conserved cysteines, are associated with autosomal dominant Robinow syndrome. One mutation has been found in all living affected members of the original family described by Meinhard Robinow and another in a second unrelated patient. These missense mutations result in decreased WNT5A activity in functional assays of zebrafish and Xenopus development. This work suggests that a WNT5A/ROR2 signal transduction pathway is important in human craniofacial and skeletal development and that proper formation and growth of these structures is sensitive to variations in WNT5A function. Developmental Dynamics 239:327–337, 2010. © 2009 Wiley‐Liss, Inc.
Prediction and embodiment in dialogue
Authors: Pickering Martin J. , Garrod Simon
Published: November 2009

We argue that embodiment (via use of action‐based representations) plays a crucial role in dialogue. To illustrate the argument we use studies of language comprehension. We first compare two distinct literatures, one concerned with the activation of non‐linguistic action‐based representations of meaning, and the other with representations of linguistic form associated with language production. We then argue that both types of embodiment support emulation and prediction. Hence, such embodiment enables addressees to anticipate both what their partner is likely to say next and what she is likely to do. We conclude by suggesting that such anticipation is essential for fluent and timely social interactions. Copyright © 2009 John Wiley & Sons, Ltd.
Estimating parameters of the channel width–flow discharge relation using rill and gully channel junction data
Authors: Pilar Salvador Sanchis M. , Torri Dino , Borselli Lorenzo , Bryan Rorke , Poesen Jean , Yañez Marta S. , Cremer Cati
Published: November 2009

Eroding channels can usually be characterized by a power relationship between channel width (W) and channel discharge (Q). This paper examines the WQ relation using a recently developed channel junction approach to extend the validity of the WQ relation and to develop a procedure for estimating the WQ exponent and proportionality coefficient. Rill and gully channel data from the literature, and new data collected in different badland areas and in a few forest mountain streams, are analysed. Analysis shows that the WQ relation for channel width collected in badlands and forests agrees with trends observed for cropland. The exponent increases with increasing channel width in a continuous fashion rather than in a step‐like way and tends to a maximum whose value ranges between 0·5 and 0·6.

The proportionality coefficient can be split into two terms, one expressing the case in which an eroding channel can broaden, the other reflecting the difficulties in removing the less erodible clods or rock fragments from the channel bed. Its splitting allows the development of a more correct form of the WQ relation in agreement with modern approaches of channel geometry: one part has the dimension of a discharge and makes the power base dimensionless, while the other brings the dimension of a length, needed for the channel width, into the WQ relation. The interpretation of the two constants is supported by data collected in rainfall‐runoff simulation experiments conducted in the field. Values characterizing the two constants in some environments are also given. Nevertheless the approach is not sufficiently parameterized yet to be of practical use (e.g. in models or for estimating peak discharge in areas where rill channels have formed). Copyright © 2009 John Wiley & Sons, Ltd.