bluuebunny/crossref_metadata_2025 huggingface dataset:
A possible role of autogenous IFN‐β for cytokine productions in human fibroblasts
Authors: Sano Emiko , Ohashi Kensaku , Sato Yuichiro , Kashiwagi Masamitsu , Joguchi Atsuhiro , Naruse Norio
Published: November 2006

It has been already known that human diploid fibroblasts are able to produce not only high levels of IFN‐β but also various kinds of cytokines by poly rI: poly rC, and some inflammatory cytokines are induced by IFN‐β gene activation. We also obtained similar results. However, in our system, cytokine productions were extremely enhanced by treating the cells with a low dose of type 1 IFN and the priming effects on cytokine productions were blocked by cycloheximide similar to those on IFN‐β productions. Most of cytokines were produced later than IFN‐β and synthesis patterns of their mRNA showed the same phenomena. We made clear that cytokine productions by poly rI: poly rC are mediated by secreted IFN‐β at a protein level using a monoclonal antibody against human IFN‐β. Further, it was shown that intra‐cellular IFN‐β which is not secreted might also participate in cytokine productions. Meanwhile, IL‐1β induced various kinds of cytokines in human fibroblasts and production time courses of these cytokines were similar to those of poly rI: poly rC induced cytokines. Although secreted IFN‐β was not detected in IL‐1β stimulated culture, expression of IFN‐β mRNA was augmented. These results showed that priming effects of type 1 IFN on cytokine productions by poly rI: poly rC might not be the direct action, but successive IFN‐β production might be essential in the production processes of other cytokines. Further, it was suggested that inducible IFN‐β might also take part in IL‐1β‐induced cytokine productions. J. Cell. Biochem. 100: 1459–1476, 2007. © 2006 Wiley‐Liss, Inc.
Expression of RBM5‐related factors in primary breast tissue
Authors: Rintala‐Maki Nina D. , Goard Carolyn A. , Langdon Colleen E. , Wall Vanessa E. , Traulsen Kathryn E.A. , Morin Cory D. , Bonin Michel , Sutherland Leslie C.
Published: November 2006

The aim of this study was to examine the expression of the RBM5 tumor suppressor, in relation to RBM6 and RBM10, to obtain a better understanding of the potential role played by these RBM5‐related factors in the regulation of RBM5 tumor‐suppressor activity. Paired non‐tumor and tumor samples were obtained from 73 breast cancer patients. RNA and protein expression were examined by semi‐quantitative reverse transcription‐polymerase chain reaction and immunoblot, respectively. Data were analyzed using various statistical methods to test for correlations amongst the RBM5‐related factors, and between the factors and various pathological parameters. Most notably, RBM5, RBM10v1, and HER2 protein expression levels were elevated in tumor tissue (P < 0.0001). RBM5 and RBM10v1 protein expression were significantly positively correlated (P < 0.001), as were RBM5 and HER2 protein expression (P < 0.01), in both non‐tumor and tumor tissue, whereas RBM10v1 and HER2 protein expression were only marginally correlated, in non‐tumor tissue (P < 0.05). Interestingly, RBM5 and RBM10v1 protein expression were both deregulated in relation to RNA expression in tumor tissue. RBM10v2 and RBM6 RNA were highly significantly positively correlated in relation to various factors relating to poor prognosis (P < 0.0001). To our knowledge, this study is the first to examine RBM5 expression at both the RNA and protein level in primary breast tumor tissue, and the first to examine expression of all RBM5‐related factors in a comprehensive manner. The results provide a graphic illustration that RBM5‐related factors are significantly differentially expressed in breast cancer, and suggest complex inter‐related regulatory networks involving alternative splicing, oncogenic expression, and tissue‐specific function. J. Cell. Biochem. 100: 1440–1458, 2007. © 2006 Wiley‐Liss, Inc.
Impact of silencing HO‐2 on EC‐SOD and the mitochondrial signaling pathway
Authors: Turkseven S. , Drummond G. , Rezzani R. , Rodella L. , Quan S. , Ikehara S. , Abraham N.G.
Published: November 2006

The contribution of heme oxygenase HO‐2, the primary source of bilirubin and carbon monoxide (CO) under physiological conditions, to the regulation of vascular function has remained largely unexplored. Using siRNA HO‐2, we examined the effect of suppressed levels of HO‐2 on vascular antioxidant and survival proteins. In vivo HO‐2 siRNA treatment decreased the basal levels of EC‐SOD, pAKT proteins (serine‐473 and threonine‐308), without changing Akt protein expression. HO‐2 siRNA treatment increased 3‐nitrotyrosine (3‐NT) and apoptotic signaling kinase‐1 (ASK‐1) (P < 0.01). HO activity was decreased by the use of siRNA HO‐2. We extended these studies to the mitochondria, examining for the presence of HO‐1 and its role in the regulation of pro‐ and anti‐apoptotic proteins. HO activity was increased by the administration of CoPP resulting in the translocation of HO‐1 into the mitochondria, mainly to the inner face of the mitochondrial inner membrane. These findings suggest that HO‐2 is critical in the maintenance of heme homeostasis and also the regulation of apoptosis by controlling levels of EC‐SOD, Akt, 3‐NT, and ASK‐1. In addition, localization of HO‐1 in the mitochondrial compartment plays a critical role in mitochondria‐mediated apoptosis. J. Cell. Biochem. 100: 815–823, 2007. © 2006 Wiley‐Liss, Inc.
Differential signal transduction of alternatively spliced FGFR2 variants expressed in human mammary epithelial cells
Authors: Moffa Allison B. , Ethier Stephen P.
Published: November 2006

Gene amplification and protein overexpression of fibroblast growth factor receptor 2 (FGFR2) characterize the SUM‐52 breast cancer cell line developed in our laboratory. SUM‐52 cells express nine distinct alternatively spliced isoforms of FGFR2. Among these isoforms are two otherwise identical FGFR2 variants that express either the C1 or C3 carboxyl terminus. FGFR2‐C3 variants are not normally expressed by human mammary epithelial (HME) cells, and we have shown that overexpression of FGFR2‐C3 in HME cells results in potent transformation. In particular, FGFR2‐C3 expression leads to robust levels of constitutively tyrosine phosphorylated FRS2 in the absence of ligand stimulation. In contrast, overexpressed FGFR2‐C1 requires constant stimulation with exogenous keratinocyte growth factor (KGF) to mimic the signaling capability of FGFR2‐C3. However, activation of FRS2 that results from KGF‐stimulated FGFR2‐C1 signaling is transient and is associated with a mobility shift of FRS2 not observed when this signaling molecule is activated by the C3 isoform of FGFR2. Mutation of the only tyrosine phosphorylated site present in the C1 terminus and absent from C3, Tyr769, did not yield a receptor that rivaled the potent signaling of FGFR2‐C3. We therefore conclude that aberrant expression of alternatively spliced isoforms of FGFR2 with the C3 carboxyl terminus in the SUM‐52 breast cancer cells results in sustained activation of signal transduction leading to transformation. J. Cell. Physiol. 210: 720–731, 2007. © 2006 Wiley‐Liss, Inc.
ERK1/2‐driven and MKP‐mediated inhibition of EGF‐induced ERK5 signaling in human proximal tubular cells
Authors: Sarközi Rita , Miller Bradley , Pollack Verena , Feifel Elisabeth , Mayer Gert , Sorokin Andrey , Schramek Herbert
Published: November 2006

The MEK1‐ERK1/2 signaling pathway has been implicated in the regulation of renal epithelial cell proliferation, epithelial‐to‐mesenchymal transition and the induction of an invasive cell phenotype. Much less information is available about the MEK5‐ERK5 module and its role in renal epithelial cell proliferation and differentiation. In the present study we have investigated the regulation of these two families of extracellular signal‐regulated kinases in epidermal growth factor (EGF)‐stimulated human kidney‐2 (HK‐2) cells and a possible interaction between ERK1/2 and ERK5. Here we report that 5 ng/ml EGF led to a strong stimulation of HK‐2 cell proliferation, which was largely U0126‐sensitive. Both synthetic MEK1/2 inhibitors U0126 and Cl‐1040, when used at 10 and 1 µM, respectively, inhibited basal and EGF‐induced ERK1/2 phosphorylation but not ERK5 phosphorylation. Long‐term inhibition of MEK1/2‐ERK1/2 signaling and/or vanadate‐sensitive protein phosphatases enhanced and prolonged EGF‐induced ERK5 phosphorylation, while transient expression of an adenoviral constitutively active MEK1 (Ad‐caMEK1) construct completely blocked EGF‐induced ERK5 phosphorylation. Expression of Ad‐caMEK1 in HK‐2 cells resulted in the upregulation of the dual‐specificity phosphatases MKP‐3/DUSP6, MKP‐1/DUSP1, and DUSP5. The EGF‐mediated time‐dependent induction of MKP‐3, MKP‐1 and DUSP5 mRNA levels was U0126‐sensitive at a concentration, which blocked EGF‐mediated ERK1/2 phosphorylation but not ERK5 phosphorylation. Furthermore, U0126 inhibited EGF‐induced MKP‐3 and MKP‐1 protein expression. Both MKP‐3 and MKP‐1 co‐immunoprecipitated with ERK5 in unstimulated as well as in EGF‐stimulated HK‐2 cells. These results suggest the existence of an ERK1/2‐driven negative feed‐back regulation of ERK5 signaling in EGF‐stimulated HK‐2 cells, which is mediated by MKP‐3, DUSP5 and/or MKP‐1. J. Cell. Physiol. 211: 88–100, 2007. © 2006 Wiley‐Liss, Inc.
Granulocyte colony‐stimulating factor promotes the translocation of protein kinase Cι in neutrophilic differentiation cells
Authors: Kanayasu‐Toyoda Toshie , Suzuki Takayoshi , Oshizawa Tadashi , Uchida Eriko , Hayakawa Takao , Yamaguchi Teruhide
Published: November 2006

Previously, we suggested that the phosphatidylinositol 3‐kinase (PI3K)‐p70 S6 kinase (p70 S6K) pathway plays an important role in granulocyte colony‐stimulating factor (G‐CSF)‐dependent enhancement of the neutrophilic differentiation and proliferation of HL‐60 cells. While atypical protein kinase C (PKC) has been reported to be a regulator of p70 S6K, abundant expression of PKCι was observed in myeloid and lymphoid cells. Therefore, we analyzed the participation of PKCι in G‐CSF‐dependent proliferation. The maximum stimulation of PKCι was observed from 15 to 30 min after the addition of G‐CSF. From 5 to 15 min into this lag time, PKCι was found to translocate from the nucleus to the membrane. At 30 min it re‐translocated to the cytosol. This dynamic translocation of PKCι was also observed in G‐CSF‐stimulated myeloperoxidase‐positive cells differentiated from cord blood cells. Small interfering RNA for PKCι inhibited G‐CSF‐induced proliferation and the promotion of neutrophilic differentiation of HL‐60 cells. These data indicate that the G‐CSF‐induced dynamic translocation and activation processes of PKCι are important to neutrophilic proliferation. J. Cell. Physiol. 211: 189–196, 2007. © 2006 Wiley‐Liss, Inc.
X‐ray microanalysis of biological material in the frozen‐hydrated state by PIXE
Authors: Tylko Grzegorz , Mesjasz‐Przybyłowicz Jolanta , Przybyłowicz Wojciech J.
Published: November 2006

Elemental microanalysis of biological material in the frozen‐hydrated state using in‐vacuum proton induced X‐ray emission is described for the first time. For this purpose, a commercially available cryotransfer system was modified and coupled to the experimental chamber of the nuclear microprobe (NMP). The analyzed material was frozen in propane cooled by liquid nitrogen, fractured, carbon coated, and transferred onto the cold stage (100 K) of the nuclear microprobe chamber. Micro‐PIXE and simultaneous proton backscattering was performed using a 3 MeV proton beam. Quantitative results were obtained by the standardless method, and tested using 20% gelatin standards. Monitoring of the gas composition inside the system by means of mass spectrometry performed before, during, and after proton bombardment showed good stability of the analyzed material for proton currents not exceeding 150 pA. Average concentrations of light elements (C, N, O, and indirectly H) were also obtained by the proton backscattering technique. No losses of elements measurable by particle‐induced X‐ray emission (PIXE) during proton irradiation were found during repetitive, short analyses of the same micro areas of gelatin standards. Measurements of thick sections of selected plant and animal material in the frozen‐hydrated state–leaf sections of the plant Senecio anomalochrous Hilliard (Asteraceae) and larvae of Chysolina pardalina Fabricius (Chrysomelidae)–showed very good preservation of morphology and elemental distribution. Limits of detection of the order of a few μg g−1 were obtained for most elements. Microsc. Res. Tech., 2007. © 2006 Wiley‐Liss, Inc.
Heterogeneity in informal sector mitigation of micro‐enterprise credit rationing
Authors: Mushinski David W. , Pickering Kathleen A.
Published: November 2006

Economists have observed that informal credit markets may mitigate micro‐entrepreneurial rationing in formal credit markets. While informal credit markets may have that effect, the uniformity and magnitude of the mitigation is not apparent. We analyse micro‐enterprise credit rationing on the Pine Ridge Indian Reservation in the United States. We find that micro‐entrepreneurs have virtually no access to formal credit markets and that informal credit markets have differential impacts on micro‐entrepreneurs' rationing in formal credit markets. Informal markets appear to ease credit rationing the most for the mid‐size micro‐enterprises in our sample, with the smallest and largest micro‐enterprises still facing severe rationing constraints. We also find that micro‐enterprises of all sizes face a positive probability of credit rationing. Copyright © 2006 John Wiley & Sons, Ltd.
Progression towards AIDS leads to increased torque teno virus and torque teno minivirus titers in tissues of HIV infected individuals
Authors: Thom K. , Petrik J.
Published: November 2006

Torque teno virus (TTV) and Torque teno minivirus (TTMV) are highly prevalent in the general population and although no disease has been associated with these viruses yet, co‐infections with other pathological viruses are frequent. Both viruses are extremely heterogeneous, especially for DNA viruses, and the role of the immune system in controlling the infections has yet to be established. In this study the TTV/TTMV viral loads in HIV positive tissues have been investigated for the first time. The titers of both TTV and TTMV were compared in the bone marrow and spleen tissues from three groups: HIV negative individuals, HIV positive individuals and HIV positive individuals who had progressed to AIDS, leading to immunosuppression. Limiting dilution PCR using primers situated in the UTR region of the genome were used to semi‐quantitate the virus, and TTV and TTMV were differentiated using melting curve analysis of the PCR product. The AIDS group had significantly higher titers compared with both the HIV positive and negative groups for both bone marrow (AIDS vs. HIV positive P = 0.006, AIDS vs. HIV negative P < 0.001) and spleen (AIDS vs. HIV positive P = 0.022, AIDS vs. HIV negative P < 0.001). Analysis of TTV/TTMV titer with CD4 T lymphocyte count showed a significant inverse correlation however neither HCV co‐infection or type of Anellovirus infection (single TTV or TTMV, or mixed TTV/TTMV) showed any significant correlation with virus titer. The results show a link between deterioration of the immune system and increased the viral loads in studied tissues. J. Med. Virol. 79:1–7, 2007. © 2006 Wiley‐Liss, Inc.
Comparison of hepatitis A and E virus infections among healthy children in Mongolia: Evidence for infection with a subgenotype IA HAV in children
Authors: Tsatsralt‐Od Bira , Takahashi Masaharu , Endo Kazunori , Agiimaa Dondog , Buyankhuu Osorjin , Okamoto Hiroaki
Published: November 2006

To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in children in Mongolia, the prevalence of HAV and HEV infections was investigated serologically and molecularly among 717 apparently healthy individuals of 0–20 years of age (mean ± standard deviation, 8.6 ± 4.9 years) using serum samples obtained between October 2005 and January 2006. Total antibody against HAV (anti‐HAV [total]) was detected in 494 (68.9%) of the 717 subjects, while IgG antibody against HEV (anti‐HEV IgG) was detected in only five subjects (0.7%) (P < 0.0001). All five subjects who had anti‐HEV IgG, were negative for anti‐HEV IgM and HEV RNA. Anti‐HAV was detectable in 24 (75.0%) of the 32 infants aged 7 days to 6 months, but not in any of the 8 infants aged 7 to <12 months. The prevalence of anti‐HAV was 19.5% (17/87) in the age group of 1–3 years, and it increased to 50.0% (69/138) in the age group of 4–6 years, and further to 81.4% (105/129) in the age group of 7–9 years. Of note, 97.2% of the subjects in the age group of 16–20 years had anti‐HAV. The presence of HAV RNA was tested in all 717 subjects, and three children of 1, 4, or 8 years of age were found to have detectable HAV RNA (subgenotype IA). No subject had a history of hepatitis or jaundice. In conclusion, HEV infection was uncommon, but HAV infection lacking overt clinical features was prevalent among children in Mongolia. J. Med. Virol. 79:18–25, 2007. © 2006 Wiley‐Liss, Inc.
Genetic diversity of HCV genotype 2 strains in South Western France
Authors: Thomas Fabienne , Nicot Florence , Sandres‐Sauné Karine , Dubois Martine , Legrand‐Abravanel Florence , Alric Laurent , Peron Jean‐Marie , Pasquier Christophe , Izopet Jacques
Published: November 2006

Hepatitis C virus (HCV) is a major cause of chronic hepatitis and liver disease worldwide. The genetic heterogeneity of HCV and its spread among infected patients can be examined accurately by nucleotide sequencing. The diversity of HCV genotype 2 strains (HCV‐2) was studied in a large cohort of patients in the Midi Pyrénées area of southern France. Phylogenetic analysis was performed on 344 NS5B sequences from patients infected with HCV‐2. These included 145 strains whose E2 region was also analyzed, and epidemiological data were collected for the corresponding patients. HCV‐2 accounts for 11.3% of HCV infections in this area. Phylogenetic analysis of NS5B sequences revealed eight subtypes, while that of the E2 region provided congruent results for 100% of strains. The most frequent subtypes were 2i (24.7%), 2k (22.4%) 2c (17.4%), and 2a (10.8%). The mean age of HCV‐2‐infected patients was 55.5 years. Epidemiological data showed that blood transfusion is the major route of infection, but it was not associated with any particular subtype. By contrast, intravenous drug users were infected predominantly with genotype 2a. HCV‐2a‐infected patients were younger than patients infected with other subtypes (48 vs. 56.5 years, P < 0.01). This study shows substantial genetic diversity of HCV‐2 subtypes in the south of France and the spread of 2a strains via intravenous drug users. J. Med. Virol. 79:26–34, 2007. © 2006 Wiley‐Liss, Inc.
A mutation in the interferon sensitivity‐determining region is associated with responsiveness to interferon‐ribavirin combination therapy in chronic hepatitis patients infected with a Japan‐specific subtype of hepatitis C virus genotype 1b
Authors: Murayama Mutsumi , Katano Yoshiaki , Nakano Isao , Ishigami Masatoshi , Hayashi Kazuhiko , Honda Takashi , Hirooka Yoshiki , Itoh Akihiro , Goto Hidemi
Published: November 2006

The interferon sensitivity‐determining region (ISDR) is useful as a predictive marker of the response to interferon (IFN) therapy for chronic hepatitis patients with a Japan‐specific subtype (J‐type) of hepatitis C virus (HCV) genotype 1b. This marker is not useful for predicting responsiveness of a worldwide subtype (W‐type) of HCV 1b, which could explain the restricted usefulness of this system only to Japan. In the present study, we examined the predictive value of the ISDR for ribavirin combination therapy. A total of 79 patients with HCV 1b comprising 35 patients with J‐type and 44 patients with W‐type were treated with IFN in combination with ribavirin for more than 48 weeks. Mutations in the ISDR were detected more frequently often seen in J‐type HCV 1b than in W‐type; however, the sustained virological response (SVR) rate for the combination therapy was similar between the two subtypes. Multivariate analysis revealed that factors associated with SVR were IFN dose and the number of amino acid substitutions in ISDR but not with subtypes J and W. The correlation between the number of substitutions in ISDR and responses to IFN‐ribavirin combination therapy was restricted to patients with J‐type HCV 1b. The ISDR is a useful predictive marker for response to IFN‐ribavirin combination therapy in J‐type HCV. J. Med. Virol. 79:35–40, 2007. © 2006 Wiley‐Liss, Inc.
Injury‐induced Janus kinase/protein kinase C‐dependent phosphorylation of growth‐associated protein 43 and signal transducer and activator of transcription 3 for neurite growth in dorsal root ganglion
Authors: Tsai Shih‐Ying , Yang Liang‐Yo , Wu Chin‐Hsiang , Chang Shwu‐Fen , Hsu Chung Y. , Wei Chi‐Peng , Leu Sy‐Jye , Liaw Jiahorng , Lee Yi‐Hsuan , Tsai Ming‐Dar
Published: November 2006

Elevation of corticosteroids and excessive glutamate release are the two major stress responses that occur sequentially during traumatic CNS injury. We have previously reported that sequential application of corticosterone and kainic acid (CORT + KA) mimicking the nerve injury condition results in synergistic enhancement of neurite outgrowth and expression of growth‐associated protein 43 (GAP‐43) in cultured dorsal root ganglion (DRG). GAP‐43 is known to promote neurite extension when phosphorylated by protein kinase C (PKC). In addition, PKC can phosphorylate the signal transducer and activator of transcription 3 (STAT3) at Ser727, which is phosphorylated primarily by Janus kinase (JAK) at Tyr705. In this study, we further examine the role of PKC in this stress‐induced growth‐promoting effect. In the cultured DRG neurons, the JAK inhibitor AG‐490 and the PKC inhibitor Ro‐318220 reduced the CORT + KA‐enhanced neurite growth effect when applied prior to CORT and KA treatment, respectively. Both AG‐490 and Ro‐318220 diminished the CORT + KA‐enhanced GAP‐43 expression, phosphorylation, and axonal localization. Furthermore, CORT + KA treatment synergistically phosphorylated STAT3 at Ser727 but not at Tyr705. Similar phenomena were observed in an animal model of acute spinal cord injury (SCI), in which phosphorylation of GAP‐43 and phospho‐Ser727‐STAT3 was elevated in the injured DRG 4 hr after the impact injury. Further treatment with the therapeutic glucocorticoid methylprednisolone enhanced the phosphorylation of GAP‐43 in both the DRG and the spinal cord of SCI rats. These results suggest that elevated glucocorticoids and overexcitation following CNS injury contribute to nerve regeneration via induction of JAK/PKC‐mediated GAP‐43 and STAT3 activities. © 2006 Wiley‐Liss, Inc.
RNA interference‐mediated knockdown of α‐synuclein protects human dopaminergic neuroblastoma cells from MPP+ toxicity and reduces dopamine transport
Authors: Fountaine Timothy M. , Wade‐Martins Richard
Published: November 2006

The critical observation in the pathology of Parkinson's disease (PD) is that neurodegeneration is largely restricted to dopaminergic neurons that develop cytoplasmic inclusions called Lewy bodies. These aggregations contain the protein α‐synuclein. Furthermore, it is becoming apparent that α‐synuclein expression levels are a major factor in PD pathogenesis. Patients with additional copies of the α‐synuclein gene develop PD with a severity proportional to levels of α‐synuclein overexpression. Similarly, overexpression of α‐synuclein in in vitro and in vivo models has been shown to be toxic. However, little is known about the effects of reducing α‐synuclein expression in human neurons. To investigate this, we have developed a system in which levels of α‐synuclein can be acutely suppressed by using RNA interference (RNAi) in a physiologically relevant human dopaminergic cellular model. By using small interfering RNA (siRNA) molecules targeted to endogenous α‐synuclein, we achieved 80% protein knockdown. We show that α‐synuclein knockdown has no effect on cellular survival either under normal growth conditions over 5 days or in the presence of the mitochondrial inhibitor rotenone. Knockdown does, however, confer resistance to the dopamine transporter (DAT)‐dependent neurotoxin N‐methyl‐4‐phenylpyridinium (MPP+). We then demonstrate for the first time that α‐synuclein suppression decreases dopamine transport in human cells, reducing the maximal uptake velocity (Vmax) of dopamine and the surface density of its transporter by up to 50%. These results show that RNAi‐mediated α‐synuclein knockdown alters cellular dopamine homeostasis in human cells and may suggest a mechanism for the increased survival in the presence of MPP+, a toxin used extensively to model Parkinson's disease. © 2006 Wiley‐Liss, Inc.
Diverging mechanisms for TNF‐α receptors in normal mouse brains and in functional recovery after injury: From gene to behavior
Authors: Quintana Albert , Molinero Amalia , Florit Sergi , Manso Yasmina , Comes Gemma , Carrasco Javier , Giralt Mercedes , Borup Rehannah , Nielsen Finn Cilius , Campbell Iain L. , Penkowa Milena , Hidalgo Juan
Published: November 2006

Cytokines, such as tumour necrosis factor (TNF)‐α and lymphotoxin‐α, have been described widely to play important roles in the brain in physiologic conditions and after traumatic injury. However, the exact mechanisms involved in their function have not been fully elucidated. We give some insight on their role by using animals lacking either Type 1 receptor (TNFR1KO) or Type 2 (TNFR2KO) and their controls (C57Bl/6). Both TNFR1KO and to a greater extent TNFR2KO mice showed increased exploration/activity neurobehavioral traits in the hole board test, such as rearings, head dippings, and ambulations, compared with wild‐type mice, suggesting an inhibitory role of TNFR1/TNFR2 signaling. In contrast, no significant differences were observed in the elevated plus maze test, ruling out a major role of these receptors in the control of anxiety. We next evaluated the response to a freeze injury to the somatosensorial cortex. The effect of the cryolesion on motor function was evaluated with the horizontal ladder beam test, and the results showed that both TNFR1KO and TNFR2KO mice made fewer errors, suggesting a detrimental role for TNFR1/TNFR2 signaling for coping with brain damage. Expression of ∼22600 genes was analyzed using an Affymetrix chip (MOE430A) at 0 (unlesioned), 1, or 4 days post‐lesion in the three strains. The results show a unique and major role of both TNF receptors on the pattern of gene expression elicited by the injury but also in normal conditions, and suggest that blocking of TNFR1/TNFR2 receptors may be beneficial after a traumatic brain injury. © 2006 Wiley‐Liss, Inc.
Purification and spectroscopic characterization of the recombinant BG21 isoform of murine golli myelin basic protein
Authors: Bamm Vladimir V. , Ahmed Mumdooh A.M. , Ladizhansky Vladimir , Harauz George
Published: November 2006

A recombinant form of the murine Golli‐myelin basic protein (MBP) isoform BG21 (rmBG21) has been expressed in E. coli, and isolated to 96% purity via metal chelation chromatography. Characteristic yields were 6–8 mg protein per liter of culture in either minimal M9 or standard Luria‐Bertani media. Circular dichroism spectroscopy showed that rmBG21 had a large proportion of random coil in aqueous solution, but gained α‐helix in the presence of monosialoganglioside GM1 and PI(4)P, as well as in the membrane‐mimetic solvent trifluoroethanol. Bioinformatics analyses of the amino acid sequence of rmBG21 predicted an N‐terminal calmodulin (CaM)‐binding site. It was determined by fluorescence spectroscopy and dynamic light scattering that rmBG21 and CaM interacted weakly in a 1:1 ratio in a Ca2+‐dependent manner. Solution NMR spectra of uniformly [13C15N]‐labeled protein in aqueous buffer were consistent with it being an extended protein; spectral quality was independent of temperature. Thus, like “classic” MBP and the Golli‐MBP isoform J37, rmBG21 is intrinsically disordered, implying multi functionality, and that its conformation depends on its environment and bound ligands. © 2006 Wiley‐Liss, Inc.
Manipulation of proliferation and differentiation of human bone marrow‐derived neural stem cells in vitro and in vivo
Authors: Zeng Zhaohui , Yuan Xiangpeng , Liu Gentao , Zeng Xianhao , Zeng Xiaorong , Ng Hiushan , Chen Haiming , Jiang Tingxin , Akasaki Yasuharu , Kessey Kofi , Black Keith L. , Yu John S.
Published: November 2006

Recent evidence has demonstrated that neural stem cells (NSC) can be expanded from a variety of sources, including embryos, fetuses, and adult bone marrow and brain tissue. We have previously reported the generation of adult rat bone marrow‐derived cellular spheres that are morphologically and phenotypically similar to neurospheres derived from brain NSC. Here we show that adult human bone marrow‐derived neural stem cells (HBM‐NSC) are capable of generating spheres that are similar to brain neural‐derived neurospheres. Additionally, we sought to promote proliferation and differentiation of HBM‐NSC through transduction with nonreplicative recombinant adenovirus encoding the cDNA sequence for Gli, rADV‐Gli‐1; sonic hedgehog, rADV‐Shh; or Nurr1, rADV‐Nurr1. Immunocytochemistry and RT‐PCR analysis showed that HBM‐NSC could be efficiently expanded and differentiated in vitro and that HBM‐NSC transduced with rADV‐Gli‐1 or rADV‐Shh dramatically increased NSC time‐related proliferation; however, Nurr1 had no effect on proliferation. We also transplanted HBM‐NSC into chicken embryos to examine their potential function in vivo. We found that transduction of HBM‐NSC with rADV‐Gli‐1 or rADV‐Shh and subsequent transplantation into chicken embryos increased HBM‐NSC proliferation, whereas rADV‐Nurr1 promoted migration and differentiation in vivo. Our findings suggest that HBM‐NSC can be efficiently expanded and differentiated in vitro and in vivo by overexpressing Gli‐1, Shh or Nurr1. © 2006 Wiley‐Liss, Inc.
Recovery of the depolarization ratio of single lines from overlapping isotropic and anisotropic Raman profiles and assignment of molecular vibrations, with special reference to toluene and toluene‐d8
Authors: Kirillov S. A. , Morresi A. , Paolantoni M.
Published: November 2006

If a Raman line consists of several overlapping components, any attempt to perform a quantitative analysis of the wavenumber‐dependent depolarization ratio ρ(ν) fails, since ρ(ν) of a composite line is not an additive function of ρ(ν) of its constituents, and for a composite line representing an envelope of i single lines, ρcomp(ν) ≠ ∑ρi(ν). This situation causes significant difficulties in the analysis of Raman spectra, especially in the case of weak lines (overtones, combination bands, etc.) situated in the close vicinity of strong fundamentals. In this paper, a specific algorithm is employed to recover isotropic and anisotropic Raman profiles. Using toluene and toluene‐d8 as examples, it is shown that the ρ(ν) spectra of all components of a composite spectrum can be easily restored, facilitating the assignment of overtones, hot bands, and combination bands. Copyright © 2006 John Wiley & Sons, Ltd.
Re‐operative neck surgery for well‐differentiated thyroid cancer of follicular origin
Authors: Monchik Jack M. , DeLellis Ronald A.
Published: November 2006

This review focuses on the pathologic criteria for completion thyroidectomy in well differentiated thyroid cancer as well the diagnosis and treatment of recurrent disease. The roles of ultrasound in the diagnosis of a cervical recurrence, its value in determining the extent of lymph node dissection in the lateral compartment, and the importance of intra‐operative ultrasound in re‐operative thyroid surgery are discussed. J. Surg. Oncol. 2006;94:714–718. © 2006 Wiley‐Liss, Inc.
Total thyroidectomy for differentiated thyroid cancer
Authors: Sosa Julie Ann , Udelsman Robert
Published: November 2006

There has been a long debate about the optimal surgical management of differentiated thyroid cancer. It has focused on the extent of thyroidectomy, with recommendations ranging from thyroid lobectomy to total thyroidectomy. There is no randomized prospective trial addressing this issue; such a trial would be prohibitive, since differentiated thyroid cancer has a good prognosis and a long natural history. Instead, there is heavy reliance on retrospective analyses, as well as consensus expert opinion and experience. We review this evidence, along with recent recommendations from several professional associations. We believe that total or near‐total thyroidectomy followed by 131I ablation and thyroid hormone suppression are most appropriate for the majority of patients with differentiated thyroid cancer, as retrospective analyses have shown that they reduce the risk of cancer recurrence, address the chance of multifocal intrathyroidal cancer, and facilitate use of surveillance scans and thyroglobulin monitoring for post‐operative recurrence. This recommendation comes with the caveat that total thyroidectomy must be performed safely, since there is evidence that surgeon volume is associated with patient outcomes. J. Surg. Oncol. 2006;94:701–707. © 2006 Wiley‐Liss, Inc.
Effect of Na+‐MMT Platelets on Monomer Casting Polyamide 6/Polyphenylene Oxide Blends
Authors: Liu Andong , Xie Tingxiu , Yang Guisheng
Published: November 2006

Summary: Blend composites (95:5) of monomer casting polyamide 6 and polyphenylene oxide (MCPA6/PPO) with and without 0.5 wt.‐% Na+‐montmorillonite (Na+‐MMT) platelets were prepared by in situ AROP of CL using water as a pre‐dispersant of Na+‐MMT. The effect of Na+‐MMT on morphologies of MCPA6/PPO has been studied by scanning and transmission electron micrographs and rotational rheometer, respectively. The domain size of PPO dispersed phase in the MCPA6 matrix decreased significantly from some dozens of micrometers to about 1 µm and all Na+‐MMT was dispersed only in the MCPA6 phase. It is considered that the high aspect ratio of the Na+‐MMT prevented the coalescence of PPO domains during in situ polymerization. The results of DSC indicated that the size of PPO dispersed phase affected the crystalline behavior. Synergistic action of PPO and Na+‐MMT improved the strength and the toughness of nanocomposites compared with that of the pure MCPA6.

SEM micrographs of the cryo‐fractured surfaces of (A) MCPA6/PPO (95:5) and (B) MCPA6/PPO/Na+‐MMT (95:5:0.5).

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SEM micrographs of the cryo‐fractured surfaces of (A) MCPA6/PPO (95:5) and (B) MCPA6/PPO/Na+‐MMT (95:5:0.5).
Functionalization of Carbon Nanotubes with Well‐Defined Functional Polymers via Thiol‐Coupling Reaction
Authors: You Ye‐Zi , Hong Chun‐Yan , Pan Cai‐Yuan
Published: November 2006

Summary: Thiol‐reactive‐functionality decorated multi‐walled carbon nanotubes (MWNTs) have been obtained. Trithiocarbonate‐ended poly(N‐(2‐hydroxypropyl)methacrylamide) (PHPMA) is prepared by reversible addition‐fragmentation chain transfer (RAFT) polymerization of N‐(2‐hydroxypropyl)methacrylamide (HPMA) using S‐1‐dodecyl‐S′‐(α,α′‐dimethyl‐α″‐acetic acid)trithiocarbonate as chain transfer agent, subsequently, thiol‐terminated PHPMA (PHPMA‐SH) is obtained by treating trithiocarbonate‐ended PHPMA with hexylamine. The PHPMA‐S‐S‐MWNT conjugate is formed by simply stirring the mixture of thiol‐reactive‐functionality decorated MWNTs with PHPMA‐SH in phosphate buffered saline by a thiol‐coupling reaction. FT‐IR, HRTEM, 1H NMR, and TGA results show that this thiol‐coupling reaction is effective to produce aqueous soluble polymer–MWNT conjugates under mild conditions.

Thiol‐reactive‐functionality decorated multi‐walled carbon nanotubes are modified with thiol end‐capped polymers by a thiol‐coupling reaction.

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Thiol‐reactive‐functionality decorated multi‐walled carbon nanotubes are modified with thiol end‐capped polymers by a thiol‐coupling reaction.
Assessing the role of DRD5 and DYT1 in two different case–control series with primary blepharospasm
Authors: Clarimon Jordi , Brancati Francesco , Peckham Elizabeth , Valente Enza Maria , Dallapiccola Bruno , Abruzzese Giovanni , Girlanda Paolo , Defazio Giovanni , Berardelli Alfredo , Hallett Mark , Singleton Andrew B.
Published: November 2006

Primary blepharospasm is a common adult‐onset focal dystonia. Polymorphisms of the genes encoding TorsinA (DYT1) and the D5 dopamine receptor (DRD5) have previously been associated with lifetime risk for focal dystonia. We describe here experiments testing common variability within these two genes in two independent cohorts of Italian and North American patients with primary blepharospasm. We have failed to identify a consistent association with disease in the two patient groups examined here; however, analysis of the Italian group reveals an association with the same risk genotype in DYT1 as previously described in an Icelandic population. We have also found global significant DYT1 haplotype differences between patients and controls in the Italian series. These data suggest that further examination is warranted of the role genetic variability at this locus plays in the risk for primary dystonia. © 2006 Movement Disorder Society
Regional metabolic changes in Parkinsonian patients with normal dopaminergic imaging
Authors: Eckert Thomas , Feigin Andrew , Lewis Daniel E. , Dhawan Vijay , Frucht Steven , Eidelberg David
Published: November 2006

Dopaminergic imaging has been found to be normal in approximately 15% of parkinsonian patients enrolled in neuroprotective trials. We used 18F‐fluorodeoxyglucose positron emission tomography (FDG PET) to determine the metabolic basis for this finding. We reviewed scans from 185 patients with clinical signs of Parkinson's disease (PD) who underwent 18F‐fluorodopa PET imaging for diagnostic confirmation. Of this group, 27 patients (14.6%) had quantitatively normal scans; 8 of these patients were additionally scanned with FDG PET. Pattern analysis was performed on an individual scan basis to determine whether the metabolic changes were consistent with classic PD. Computer‐assisted single‐case assessments of the FDG PET scans of these 8 patients did not disclose patterns of regional metabolic change compatible with classical PD or an atypical parkinsonian variant. Similarly, network quantification revealed that PD‐related pattern expression was not elevated in these patients as it was in an age‐ and duration‐matched cohort with classical PD (P < 0.0001). None of these patients developed clinical signs of classical PD or of an atypical parkinsonian syndrome at a follow‐up visit conducted 3 years after imaging. The results suggest that parkinsonian subjects with normal dopaminergic imaging do not have evidence of classical PD or an atypical parkinsonian syndrome. © 2006 Movement Disorder Society
Brainstem respiratory control: Substrates of respiratory failure of multiple system atrophy
Authors: Benarroch Eduardo E.
Published: November 2006

Multiple system atrophy may manifest with severe respiratory disorders, including sleep apnea and laryngeal stridor, which reflect a failure of automatic control of respiration. This function depends on a pontomedullary network of interconnected neurons located in the parabrachial/Kölliker Fuse nucleus in the pons, nucleus of the solitary tract, and ventrolateral medulla. Neurons in the preBötzinger complex expressing neurokinin‐1 receptors are critically involved in respiratory rhythmogenesis, whereas serotonergic neurons in the medullary raphe and glutamatergic neurons located close to the ventral medullary surface are involved in central chemosensitivity to hypercapnia, hypoxia, or both. Pathological studies using selective neurochemical markers indicate that these neuronal groups are affected in multiple system atrophy. This finding may provide potential anatomical substrates for the respiratory manifestations of the disease. © 2006 Movement Disorder Society
The nature and influence of motivation within the MOA framework: implications for social marketing
Authors: Binney Wayne , Hall John , Oppenheim Peter
Published: November 2006

Social marketers acknowledge that to achieve optimum programme outcomes, identification and targeting of the non‐conforming cohort is paramount. This article discusses the application of the social marketing framework, motivation, opportunity and ability (MOA) with a particular focus on the motivation aspect of the model. Motivation is considered from the perspectives of intrinsic and extrinsic motivation.

Previously, the degree or level of motivation has been used in the operationalisation of the motivation construct, while in this paper the type of motivation is used as the basis for the construct. The construct is then applied to an environmental land management study, namely a rabbit control programme.

Specifically, the aims of this paper were to further develop the MOA constructs, with a particular focus on motivation, including intrinsic and extrinsic motivation, to develop an understanding of the factors that are associated with ineffective behaviour and to develop a model to predict effective/ineffective control behaviour.

Scales were developed to enable a study of the relationship between the MOA constructs, including intrinsic and extrinsic motivation, and the respondents control behaviour. Data were collected from a random sample of 566 respondents who were involved in the control programme. Using ANOVA and MANOVA techniques, significant differences were found between those landholders that exhibited effective control and ineffective control with regard to all MOA constructs.

A multinomial logit (MNL) regression model was then developed to predict behaviour. This model showed that ability and intrinsic motivation were significant predictors of behaviour. The estimated model was able to predict recalcitrant landholders with 98% accuracy. The results of this study therefore provide a significant contribution to social marketing as it is the recalcitrant cohort that social marketers wish to understand and whose behaviour they frequently attempt to rectify in order to achieve stated social and/or environmental objectives. The implications for related social market theory, policy development and environmental management programmes are discussed.

Copyright © 2006 John Wiley & Sons, Ltd.
Ethnocentric tendencies amongst arts audiences
Authors: Kottasz Rita , Bennett Roger
Published: November 2006

According to empirical research, the most regular consumers of art are well‐to‐do, well‐educated members of the social elite who, as a socio‐demographic group, would not be expected to exhibit ethnocentric tendencies. Yet, curators of arts institutions and art critics have long been concerned that ethnocentrism does exist amongst visitors to museums and art galleries. This paper reports the findings of a study that investigated the ethnocentric tendencies of arts audiences in Hungary (where, allegedly, individuals are more inclined to exhibit ethnocentric bias) and England (where the opposite is said to be true). The research examined whether ethnocentrism significantly impacted upon perceptions of artworks from (i) a visitor's own country, (ii) a culturally similar and (iii) a culturally dissimilar country. Intentions to attend art exhibitions featuring artists from these countries were then explored. The empirical analysis confirmed that individuals who exhibited ethnocentric tendencies did in fact overvalue the quality of artworks from their home country. Moreover, ethnocentrism within the Hungarian (but not the English) sample had a significant impact on intentions to visit particular types of exhibition.

Copyright © 2006 John Wiley & Sons, Ltd.
Inflation lung mechanics deteriorates markedly after saline instillation and open endotracheal suctioning in mechanically ventilated healthy piglets
Authors: Cunha‐Goncalves Doris , Perez‐de‐Sá Valéria , Ingimarsson Jónas , Werner Olof , Larsson Anders
Published: November 2006

Introduction Non‐bronchoscopic bronchoalveolar lavage is an alternative to diagnostic bronchoscopy in pediatric patients, as fiberoptic bronchoscopes with aspiration channels are too large for small infants. There are many variations of the method in clinical practice, and saline instillation followed by open endotracheal suctioning is still commonly used. Lung function can deteriorate with these procedures, and we have investigated the effects on lung mechanics and oxygenation in healthy piglets. Methods The lungs of anesthetized and mechanically ventilated piglets were recruited with CPAP 35 cmH2O. Thereafter we instilled 5 ml of saline into the endotracheal tube, followed by three breaths from the ventilator. Saline was retrieved through a suction catheter wedged far distally in the airway. The procedure was followed by a new recruitment maneuver. Complete inspiratory/expiratory pressure–volume loops (PV‐loops) were obtained just before and 5 min after saline instillation. Arterial blood gases were collected at equivalent times in 14 similar piglets submitted to exactly the same procedure. Results The inspiratory limb of the PV‐loops changed markedly, as the lower inflection point was displaced towards higher pressures (P = 0.004), and hysteresis measured at 15 and 30 cmH2O increased (P = 0.004 and P = 0.012, respectively). Although PaO2 decreased significantly (P = 0.001), values after saline instillation/suctioning were still in the high normal range, that is, 22.2 ± 2.6 kPa. Conclusions Opening pressures of the lungs increase markedly after saline instillation/suctioning in healthy piglets. In this situation, adequate recruitment maneuvers and PEEP might prevent lung collapse and deteriorations in arterial oxygenation. Pediatr Pulmonol. 2007; 42:10–14. © 2006 Wiley‐Liss, Inc.
Airway pressure release ventilation: A pediatric case series
Authors: Krishnan Jambunathan , Morrison Wynne
Published: November 2006

Airway pressure release ventilation (APRV) is a relatively new mode of mechanical ventilation (MV) first described in animal studies in 1987 and in humans in 1988. It is a time‐triggered, time‐cycled, pressure‐limited mode where a high level of continuous positive airway pressure (CPAP) is maintained with brief regular releases in pressure, and spontaneous breathing is allowed throughout the cycle. In theory, it is consistent with a lung protective approach while having some hypothetical advantages over HFOV. The use of this mode of ventilation in pediatrics has been limited. The authors describe their experience with this mode of ventilation in a series of pediatric patients. Pediatr Pulmonol. 2007; 42:83–88. © 2006 Wiley‐Liss, Inc.
Molecular design of fullerene‐based ultralow‐k dielectrics
Authors: Wang Yuekui , Seifert Gotthard , Hermann Helmut
Published: November 2006

The article [1] presents results of a quantum‐theoretical study of hypothetical interlayer dielectrics for semiconducting circuits. The configuration shown in the cover picture consists of two C60 fullerenes connected by a silicon‐containing C(COO)2Si0.5 molecule. This fullerene dimer acts as basic structural unit of a fullerene polymer proposed as a new insulating material with extremely low dielectric constant of k = 1.5 for application in future devices.

The work is a joint collaboration of IFW (H. Hermann), Technical University Dresden (G. Seifert), and AMD Saxony while Y. Wang was a guest scientist working on this project together with his co‐authors. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)