bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and mutational analysis of MET in human solid cancers
Authors: Ma Patrick C. , Tretiakova Maria S. , MacKinnon Alexander C. , Ramnath Nithya , Johnson Candace , Dietrich Sascha , Seiwert Tanguy , Christensen James G. , Jagadeeswaran Ramasamy , Krausz Thomas , Vokes Everett E. , Husain Aliya N. , Salgia Ravi
Published: August 2008

MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) regulate a variety of cellular functions, many of which can be dysregulated in human cancers. Activated MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis. We performed systematic analysis of the expression of the MET receptor and its ligand HGF in tumor tissue microarrays (TMA) from human solid cancers. Standard immunohistochemistry (IHC) and a computerized automated scoring system were used. DNA sequencing for MET mutations in both nonkinase and kinase domains was also performed. MET was differentially overexpressed in human solid cancers. The ligand HGF was widely expressed in both tumors, primarily intratumoral, and nonmalignant tissues. The MET/HGF likely is functional and may be activated in autocrine fashion in vivo. MET and stem cell factor (SCF) were found to be positively stained in the bronchioalevolar junctions of lung tumors. A number of novel mutations of MET were identified, particularly in the extracellular semaphorin domain and the juxtamembrane domain. MET‐HGF pathway can be assayed in TMAs and is often overexpressed in a wide variety of human solid cancers. MET can be activated through overexpression, mutation, or autocrine signaling in malignant cells. Mutations in the nonkinase regions of MET might play an important role in tumorigenesis and tumor progression. MET would be an important therapeutic antitumor target to be inhibited, and in lung cancer, MET may represent a cancer early progenitor cell marker. © 2008 Wiley‐Liss, Inc.
Multiple recurrent chromosomal breakpoints in mantle cell lymphoma revealed by a combination of molecular cytogenetic techniques
Authors: Salaverria Itziar , Espinet Blanca , Carrió Ana , Costa Dolors , Astier Laura , Slotta‐Huspenina Julia , Quintanilla‐Martinez Leticia , Fend Falko , Solé Francesc , Colomer Dolors , Serrano Sergio , Miró Rosa , Beà Sílvia , Campo Elías
Published: August 2008

Mantle cell lymphoma (MCL) is genetically characterized by 11q13 translocations leading to the overexpression of CCND1, and additional secondary genomic alterations that may be important in the progression of this disease. We have analyzed 22 MCL cases and 10 MCL cell lines using multicolor fluorescence in situ hybridization (M‐FISH), FISH, and comparative genomic hybridization (CGH). The 19 cases with abnormal karyotype showed the t(11;14)(q13;q32) translocation and, additionally, 89% of cases showed both numerical (n = 58) and structural (n = 77) aberrations. All but one MCL cell line showed t(11;14) and structural and numerical alterations in highly complex karyotypes. Besides 11 and 14, the most commonly rearranged chromosomes were 1, 8, and 10 in the tumors and 1, 8, and 9 in the cell lines. No recurrent translocations other than the t(11;14) were identified. However, we identified 17 recurrent breakpoints, the most frequent being 1p22 and 8p11, each observed in four cases and two cell lines. Interestingly, five tumors and four cell lines displayed a complex t(11;14), cryptic in one case and two cell lines, preferentially involving chromosome 8. In typical MCL, ATM gene deletions were significantly associated with a high number of structural and numerical alterations. In conclusion, MCL does not have recurrent translocations other than t(11;14), but shows recurrent chromosomal breakpoints. Furthermore, most MCL harbor complex karyotypes with a high number of both structural and numerical alterations affecting several common breakpoints, leading to various balanced and unbalanced translocations. © 2008 Wiley‐Liss, Inc.
Astrocytes are very sensitive to develop innate immune responses to lipid‐carried short interfering RNA
Authors: Gorina Roser , Santalucia Tomàs , Petegnief Valérie , Ejarque‐Ortiz Aroa , Saura Josep , Planas Anna M.
Published: August 2008

Short interfering RNA (siRNA) inhibits the synthesis of specific proteins through RNA interference (RNAi). However, siRNA can induce innate immune responses that are mediated by toll‐like receptors (TLRs) in cells of the immune system. Here, we sought to evaluate whether siRNA can induce such responses in glial cells. We examined the effects of various siRNA sequences prepared with lipids (oligofectamine). Lipid‐siRNA induced variable degrees of silencing‐independent nonspecific effects, e.g. increased Stat1 and Cox‐2 expression and release of IL‐6 and IP‐10 in primary astroglia. This was prevented through chemical modification of siRNA by nucleoside 2′‐O‐methylation, without impairing specific gene silencing. Lipid‐siRNA also induced nonspecific responses in purified astroglia, but not in microglia, or 3T3 cells. The highest TLR7 and TLR3 mRNA expression was found in microglia and purified astroglia, respectively. Accordingly, the TLR3 agonist poly(I:C) (PIC) induced higher release of IFN‐β in primary and purified astroglia than in microglia. As siRNA, PIC induced IP‐10, Stat1, VCAM‐1, and Cox‐2 and increased TLR3 mRNA expression. The effects of lipid‐siRNA in purified astrocytes were attenuated after silencing TLR3 or TLR7 expression, and by the PKR inhibitor 2‐aminopurine. Furthermore, lipid‐siRNA induced the expression of RIG‐I. In contrast, siRNA devoid of lipids did not enter the astrocytes, did not silence gene expression, and did not induce Stat1 or Cox‐2. The results show that, in astroglia, lipid‐siRNA induces innate immune responses that are mediated, at least in part, by intracellular mechanism dependent on TLR7, TLR3, and helicases. © 2008 Wiley‐Liss, Inc.
Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zone
Authors: Danilov Alexandre I. , Gomes‐Leal Walace , Ahlenius Henrik , Kokaia Zaal , Carlemalm Eric , Lindvall Olle
Published: August 2008

Neural stem cells (NSCs) in the subventricular zone (SVZ) continuously generate olfactory bulb interneurons in the adult rodent brain. Based on their ultrastructural and antigenic properties, NSCs, transient amplifying precursor cells, and neuroblasts (B, C, and A cells, respectively) have been distinguished in mouse SVZ. Here, we aimed to identify these cell types in rat SVZ ultrastructurally and at the light microscopy level, and to determine the antigenic properties of each cell type using gold and fluorescence immunolabeling. We found astrocytes with single cilia (NSCs, correspond to B cells) and neuroblasts (A cells). We also observed mitotic cells, ependymal cells, displaced ependymal cells, and mature astrocytes. In contrast, transient amplifying precursor cells (C cells) were not detected. The NSCs and neuroblasts had epidermal growth factor receptor (EGFR) and platelet‐derived growth factor receptor alpha (PDGFRα) expressed on the ciliary apparatus and were the only cell types incorporating the proliferation marker BrdU. Throughout mitosis, EGFR and PDGFRα were associated with the microtubule of the mitotic spindle. Ependymal and displaced ependymal cells also expressed EGFR and PDGFRα on their cilia but did not incorporate BrdU. Our findings indicate that the NSCs in adult rat SVZ give rise directly to neuroblasts. During mitosis, the NSCs disassemble the primary cilium and symmetrically distribute EGFR and PDGFRα among their progeny. © 2008 Wiley‐Liss, Inc.
The localization and non‐genomic function of the membrane‐associated estrogen receptor in oligodendrocytes
Authors: Hirahara Yukie , Matsuda Ken‐Ichi , Gao Wen , Arvanitis Dina N. , Kawata Mitsuhiro , Boggs Joan M.
Published: August 2008

There is general acceptance that the estrogen receptor can act as a transcription factor. However, estrogens can also bind to receptors that are located at the plasma membrane and stimulate rapid intracellular signaling processes. We recently showed that a membrane‐associated estrogen receptor (mER) is present within myelin and at the oligodendrocyte (OL) plasma membrane. To understand the physiological function of mER in OLs, we investigated its cellular localization and involvement in rapid signaling in CG4 cells and OL primary cultures. An ERα was expressed along the lacy network of veins in the membrane sheets and in the perikaryon and nucleus in OLs. ERβ was located in the nucleus, and to a lesser extent along the veins. The expression of ERα and ERβ in OL membranes was confirmed by Western analysis of isolated membranes. OL membranes mainly had truncated forms of ERα, 53 and 50 kDa, in addition to some 65 kDa form, whereas ERβ was a 54 kDa form. CG4 cells and OLs were pulsed with 17α‐ and 17β‐estradiol for various times and the total lysates were analyzed for phosphorylated kinases. Both 17α‐ and 17β‐estradiol elicited rapid phosphorylation of p42/44MAPK, Akt, and GSK‐3β within 8 min. This rapid signaling is consistent with estradiol ligation of a membrane form of ER. Since 17α‐estradiol is produced at higher concentrations than 17β‐estradiol in the brain of both sexes, signaling via 17α‐estradiol‐liganded mER may have an important function in OLs. © 2008 Wiley‐Liss, Inc.
Mitogen‐activated protein kinase‐signaling stimulates Müller glia to proliferate in acutely damaged chicken retina
Authors: Fischer Andy J. , Scott Melissa A. , Tuten William
Published: August 2008

Müller glia in the mature retina have the capacity to become progenitor‐like cells in a many different vertebrate classes. The cell‐signaling pathways that control the ability of mature Müller glia to become progenitor‐like cells remain uncertain. The purpose of this study was to investigate the roles of the Mitogen‐Activated Protein Kinase (MAPK) pathway in regulating the activity of Müller glia in the chicken retina. In response to acute retinal damage, we found that Müller glia accumulated phosphorylated ERK1/2 and phospho‐CyclicAMP Response Element Binding‐protein (pCREB), and transiently expressed immediate early genes, cFos and Egr1, that are known to be downstream of MAPK‐signaling. Egr1 and pCREB were normally expressed by retinal progenitors in the circumferential marginal zone (CMZ), whereas cFos and pERK1/2 were not. In addition, small molecule inhibitors of MEK (UO126) and the FGF‐receptor (SU5402) suppressed the proliferation of Müller glia‐derived progenitor‐like cells. These inhibitors suppressed the accumulation of Egr1 and pCREB, whereas levels of cFos were unaffected in the glial cells. These findings suggest that Egr1 and pCREB are downstream of the signaling cascade activated by FGF‐receptors and ERK1/2. Further, our findings suggest that Egr1 and pCREB may promote glial proliferation. We propose that activation of both the FGF‐receptor and ERK1/2‐pathway is required for the proliferation and transdifferentiation of Müller glia into progenitor‐like cells. © 2008 Wiley‐Liss, Inc.
Night‐time work predisposes to non‐Hodgkin lymphoma
Authors: Lahti Tuuli A. , Partonen Timo , Kyyrönen Pentti , Kauppinen Timo , Pukkala Eero
Published: August 2008

Our aim was to find out whether non‐Hodgkin lymphoma (NHL) was more common than expected among night‐time shift workers. The Finnish job‐exposure matrix (FINJEM) provided estimates of the proportion of exposed persons and the mean level of exposure among the exposed in each occupation. The probability of night‐time work in each occupation was assessed, the observed and expected numbers of cancer cases in a cohort of persons born in 1906–1945 during the years of 1971–1995 were calculated, and the cumulative index of night‐time work was scored. The cohort compromised of 1,669,272 persons of whom 6,307 (3,813 men and 2,494 women) had NHL during the follow‐up. Night‐time work increased significantly (p = 0.01) the risk of NHL in men, the overall relative risk being 1.10 (95% confidence interval of 1.03–1.19). Using the lag period of 10 years, the risk ratio was 1.28 (1.03–1.59) for men who worked in night‐time shifts to a high degree as compared with those who had not been exposed to night‐time work. Night‐time workers are cancer prone and have a greater risk of NHL than population on average. © 2008 Wiley‐Liss, Inc.
Frequent promoter hypermethylation and transcriptional downregulation of the NDRG2 gene at 14q11.2 in primary glioblastoma
Authors: Tepel Martin , Roerig Peter , Wolter Marietta , Gutmann David H. , Perry Arie , Reifenberger Guido , Riemenschneider Markus J.
Published: August 2008

The N‐myc downstream‐regulated gene 2 (NDRG2) at 14q11.2 has been reported to be downregulated in glioblastoma, and NDRG2 overexpression represses glioblastoma cell proliferation in vitro (Deng et al., Int J Cancer 2003;106;342–7). To further address the role of NDRG2 as a candidate tumor suppressor in human gliomas, we analyzed 67 astrocytic tumors (10 diffuse astrocytomas, 11 anaplastic astrocytomas, 34 primary glioblastomas and 12 secondary glioblastomas) for NDRG2 gene mutation, promoter methylation and expression at the mRNA and protein levels. Using real‐time reverse transcription PCR analysis, we found decreased NDRG2 mRNA levels in primary glioblastomas as compared to diffuse and anaplastic astrocytomas. Similarly, immunohistochemistry revealed low or absent NDRG2 protein expression in primary glioblastomas. Mutational analysis of the entire NDRG2 coding sequence did not reveal any tumor‐associated DNA sequence alterations. However, sequencing of sodium bisulfite‐modified DNA identified hypermethylation of the NDRG2 promoter region in 21 of 34 primary glioblastomas (62%). Moreover, NDRG2 promoter hypermethylation was associated with decreased NDRG2 mRNA expression. In contrast to primary glioblastomas, NDRG2 promoter hypermethylation was detected in only 1 of 11 anaplastic astrocytomas (9%) and was absent in 10 diffuse astrocytomas and 12 secondary glioblastomas. Taken together, our data support NDRG2 as a candidate tumor suppressor gene that is epigenetically silenced in the majority of primary glioblastomas, but not in lower grade astrocytomas and secondary glioblastomas. © 2008 Wiley‐Liss, Inc.
Ebselen sensitizes glioblastoma cells to Tumor Necrosis Factor (TNFα)‐induced apoptosis through two distinct pathways involving NF‐κB downregulation and Fas‐mediated formation of death inducing signaling complex
Authors: Sharma Vivek , Tewari Richa , Sk Ugir Hossain , Joseph Christy , Sen Ellora
Published: August 2008

Resistance to tumor necrosis factor (TNFα)‐induced apoptosis in various cancer cells has been attributed to the activation of the transcription factor NF‐κB. Ebselen (2‐phenyl‐1,2‐benzisoselenazol‐3[2H]one)—a selenoorganic compound is known to prevent TNFα‐mediated NF‐κB activity. As glioblastoma are resistant to the cytotoxic effect of TNFα, we investigated the potential of Ebselen in sensitizing glioma cells to TNFα‐induced apoptosis. Although treatment with Ebselen reduced viability of glioma cells, cotreatment with TNFα enhanced apoptosis further through alteration of TNFα‐mediated signaling pathways. Sensitization of TNFα activated glioma cells to apoptosis by Ebselen involved 2 pathways: (i) abrogation of TNFα induced NF‐κB activation and (ii) induction of Fas‐associated death inducing signaling complex (DISC) formation. Ebselen inhibited the prosurvival pathway mediated by NF‐κB by altering the association of TNF receptor associated factor 2 (TRAF2) with TNFα receptor associated death domain (TRADD) in the TNFR1‐TRADD‐TRAF2 complex —an interaction crucial for mediating NF‐κB activity. Ebselen also induced the formation of DISC involving Fas, Fas‐associated death domain (FADD) and active caspase 8 to transduce apoptotic signals in situations where NF‐κB function was inhibited. Cotreatment with Ebselen and TNFα induced G2/M phase arrest in cell cycle and modulated the expression of molecules involved in cell cycle progression. These results raise the possibility of overcoming resistance to TNFα‐induced apoptosis by cotreatment with organoselenium Ebselen as a strategy to kill glioma cells. © 2008 Wiley‐Liss, Inc.
Adiponectin and alcoholic fatty liver disease
Authors: Rogers Christopher Q. , Ajmo Joanne M. , You Min
Published: August 2008

Worldwide, one of the most prevalent forms of chronic disease is alcoholic fatty liver, which may progress to more severe forms of liver injury including steatohepatitis, fibrosis, and cirrhosis. The molecular mechanisms by which ethanol consumption causes accumulation of hepatic lipid are multiple and complex. Chronic ethanol exposure is thought to cause enhanced hepatic lipogenesis and impaired fatty acid oxidation by inhibiting key hepatic transcriptional regulators such as AMP‐activated kinase (AMPK), sirtuin 1 (SIRT1), PPAR‐gamma coactivator alpha (PGC‐1α), peroxisome proliferator‐activated receptor alpha (PPARα), and sterol regulatory element‐binding protein 1 (SREBP‐1). Adiponectin is an adipose‐derived hormone with a variety of beneficial biological functions. Increasing evidence suggests that altered adiponectin production in adipose tissue and impaired expression of hepatic adiponectin receptors (AdipoRs) are associated with the development of alcoholic liver steatosis in several rodent models. More importantly, studies have demonstrated a protective role of adiponectin against alcoholic liver steatosis. The hepato‐protective effect of adiponectin is largely mediated by the coordination of multiple signaling pathways in the liver, leading to enhanced fat oxidation, reduced lipid synthesis and prevention of hepatic steatosis. This review begins with an assessment of the current understanding of the role of adiponectin and its receptors in the regulation of lipid homeostasis in liver, with emphasis on their relationship to the development of alcoholic liver steatosis. Following sections will review hepatic signaling molecules involved in the protective actions of adiponectin against alcoholic fatty liver and summarize the current knowledge of regulatory mechanisms of adiponectin expression and secretion in response to chronic ethanol exposure. We will conclude with a discussion of potential strategies for treating human alcoholic fatty liver disease (AFLD), including nutritional and pharmacological modulation of adiponectin and its receptors. © 2008 IUBMB IUBMB Life, 60(12): 790–797, 2008
Comprehensive ab initio calculation and simulation on the low‐lying electronic states of TlX (X = F, Cl, Br, I, and At)
Authors: Zou Wenli , Liu Wenjian
Published: August 2008

The low‐lying electronic states of TlX (X = F, Cl, Br, I, and At) are investigated using the configuration interaction based complete active space third‐order perturbation theory [CASPT3(CI)] with spin‐orbit coupling accounted for. The potential energy curves and the corresponding spectroscopic constants are reported. The results are grossly in good agreement with the available experimental data. The absorption spectra are simulated as well to reassign the experimental bands. The present results are also useful for guiding future experimental measurements. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Three‐photon microscopy shows that somatic release can be a quantitatively significant component of serotonergic neurotransmission in the mammalian brain
Authors: Kaushalya S.K. , Desai R. , Arumugam S. , Ghosh H. , Balaji J. , Maiti S.
Published: August 2008

Recent experiments on monoaminergic neurons have shown that neurotransmission can originate from somatic release. However, little is known about the quantity of monoamine available to be released through this extrasynaptic pathway or about the intracellular dynamics that mediate such release. Using three‐photon microscopy, we directly imaged serotonin autofluorescence and investigated the total serotonin content, release competence, and release kinetics of somatic serotonergic vesicles in the dorsal raphe neurons of the rat. We found that the somata of primary cultured neurons contain a large number of serotonin‐filled vesicles arranged in a perinuclear fashion. A similar distribution is also observed in fresh tissue slice preparations obtained from the rat dorsal raphe. We estimate that the soma of a cultured neuron on an average contains about 9 fmoles of serotonin in about 450 vesicles (or vesicle clusters) of ≤370 nm average diameter. A substantial fraction (>30%) of this serotonin is released with a time scale of several minutes by K+‐induced depolarization or by para‐chloroamphetamine treatment. The amount of releasable serotonin stored in the somatic vesicles is comparable to the total serotonin content of all the synaptic vesicles in a raphe neuron, indicating that somatic release can potentially play a major role in serotonergic neurotransmission in the mammalian brain. © 2008 Wiley‐Liss, Inc.
Polyhydroxylated fullerene derivative C60(OH)24 prevents mitochondrial dysfunction and oxidative damage in an MPP+‐induced cellular model of Parkinson's disease
Authors: Cai Xiaoqing , Jia Haiqun , Liu Zhongbo , Hou Bei , Luo Cheng , Feng Zhihui , Li Wenxin , Liu Jiankang
Published: August 2008

To find effective agents for Parkinson's disease (PD) prevention and therapy, we examined the protective effects of the polyhydroxylated fullerene derivative C60(OH)24 in a 1‐methyl‐4‐phenylpyridinium (MPP+)‐induced acute cellular PD model in human neuroblastoma cells and the free radical scavenging effects in this model with an electron spin resonance (ESR) spectrometer. Pretreatment with C60(OH)24 at concentrations greater than 20 μM showed significant protective effects on MPP+‐induced loss in cell viability, decreases in mitochondrial function (including mitochondrial membrane potential and activities of complex I and II), and increases in the levels of reactive oxygen species and oxidative damage to DNA and proteins. In addition, C60(OH)24 acts as a phase 2 enzyme inducer to protect cells from MPP+‐induced decreases in expression of nuclear factor‐E2‐related factor 2, expression and activity of γ‐glutamyl cysteine ligase and level of glutathione. The ESR study showed that C60(OH)24 is a powerful radical scavenger for superoxide, hydroxyl, and lipid radicals. These data suggest that C60(OH)24 is a mitochondrial protective antioxidant with direct radical scavenging activity and indirect antioxidant inducing activity. © 2008 Wiley‐Liss, Inc.
The p75 receptor is associated with inflammatory thermal hypersensitivity
Authors: Watanabe Tomoko , Ito Toshinori , Inoue Gen , Ohtori Seiji , Kitajo Keiko , Doya Hideo , Takahashi Kazuhisa , Yamashita Toshihide
Published: August 2008

Inflammatory pain, characterized by a decrease in the nociceptive threshold, arises through the actions of inflammatory mediators, and one of the key molecules is nerve growth factor (NGF). Here we report that the administration of neutralizing antibody to the neurotrophin receptor p75 (p75NTR) blocks hyperalgesia, which develops with complete Freund's adjuvant (CFA)‐induced inflammation or with an intraplantar injection of NGF. Although CFA injection results in the up‐regulation of calcitonin gene‐related peptide (CGRP) levels in the primary sensory neurons, blocking p75NTRabolishes this effect. We further demonstrate that pro‐NGF is the predominant ligand of p75NTRin vivo. Plasmin treatment, which is intended to decompose pro‐NGF, ameliorates CFA‐induced hyperalgesia. In addition, an intraplantar injection of pro‐NGF induces hyperalgesia. These data together suggest that pro‐NGF, as well as mature NGF, binding to p75NTRplays an important role in inflammation‐induced hyperalgesia. Interference in the binding may provide a therapeutic approach for the treatment of inflammatory pain. © 2008 Wiley‐Liss, Inc.
Heterogeneous effects of distinct tocopherol analogues on NO release, cell volume, and cell death in microglial cells
Authors: Sacha Beata , Zierler Susanna , Lehnardt Seija , Weber Joerg R. , Kerschbaum Hubert H.
Published: August 2008

Tocopherols (vitamin E) are potent antioxidants as well as modulators of enzymes involved in signal transduction, like nitric oxide synthase (NOS). In primary murine microglial cells and in the microglial cell line BV‐2, α‐, γ‐, and δ‐tocopherol and α‐tocopherol acid succinate, respectively, promote nitric oxide (NO) release. The NOS inhibitors aminoguanidine and NG‐methyl‐L‐arginine (L‐NMMA) suppressed α‐ and γ‐tocopherol‐induced NO release, but had no significant effect on δ‐tocopherol‐ and α‐tocopherol acid succinate–induced NO release. In BV‐2 cells, but not in primary microglial cells, γ‐ and δ‐tocopherol and α‐tocopherol acid succinate, respectively, led to cell death, characterized by exposition of phosphatidylserine on the cell surface, chromatin condensation, changes in cell volume, and formation of blebs on the cell surface. Aminoguanidine, L‐NMMA, and the NO scavenger 2‐phenyl‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl 3‐oxide (PTIO) enhanced apoptosis in γ‐tocopherol‐exposed cells and suppressed apoptosis in δ‐tocopherol‐treated cells, but had no effect on cells supplemented with α‐tocopherol acid succinate. The NO donors sodium nitroprusside and 2‐(N,N‐diethylamino)‐diazenolate 2‐oxide enhanced apoptosis in γ‐ or δ‐tocopherol‐treated cells, but rescued cells from α‐tocopherol acid succinate–induced cell death. © 2008 Wiley‐Liss, Inc.
Differential effects of the mitochondrial uncoupling agent, 2,4‐dinitrophenol, or the nitroxide antioxidant, Tempol, on synaptic or nonsynaptic mitochondria after spinal cord injury
Authors: Patel Samir P. , Sullivan Patrick G. , Pandya Jignesh D. , Rabchevsky Alexander G.
Published: August 2008

We recently documented the progressive nature of mitochondrial dysfunction over 24 hr after contusion spinal cord injury (SCI), but the underlying mechanism has not been elucidated. We investigated the effects of targeting two distinct possible mechanisms of mitochondrial dysfunction by using the mitochondrial uncoupler 2,4‐dinitrophenol (2,4‐DNP) or the nitroxide antioxidant Tempol after contusion SCI in rats. A novel aspect of this study was that all assessments were made in both synaptosomal (neuronal)‐ and nonsynaptosomal (glial and neuronal soma)‐derived mitochondria 24 hr after injury. Mitochondrial uncouplers target Ca2+ cycling and subsequent reactive oxygen species production in mitochondria after injury. When 2,4‐DNP was injected 15 and 30 min after injury, mitochondrial function was preserved in both populations compared with vehicle‐treated rats, whereas 1 hr postinjury treatment was ineffective. Conversely, targeting peroxynitrite with Tempol failed to maintain normal bioenergetics in synaptic mitochondria, but was effective in nonsynaptic mitochondria when administered 15 min after injury. When administered at 15 and 30 min after injury, increased hydroxynonenal, 3‐NT, and protein carbonyl levels were significantly reduced by 2,4‐DNP, whereas Tempol only reduced 3‐NT and protein carbonyls after SCI. Despite such antioxidant effects, only 2,4‐DNP was effective in preventing mitochondrial dysfunction, indicating that mitochondrial Ca2+ overload may be the key mechanism involved in acute mitochondrial damage after SCI. Collectively, our observations demonstrate the significant role that mitochondrial dysfunction plays in SCI neuropathology. Moreover, they indicate that combinatorial therapeutic approaches targeting different populations of mitochondria holds great potential in fostering neuroprotection after acute SCI. © 2008 Wiley‐Liss, Inc.
Neuroprotective effects of acetyl‐L‐carnitine on neuropathic pain and apoptosis: A role for the nicotinic receptor
Authors: Di Cesare Mannelli Lorenzo , Ghelardini Carla , Calvani Menotti , Nicolai Raffaella , Mosconi Luigi , Toscano Annarita , Pacini Alessandra , Bartolini Alessandro
Published: August 2008

Several pathologies related to nervous tissue alterations are characterized by a chronic pain syndrome defined by persistent or paroxysmal pain independent or dependent on a stimulus. Pathophysiological mechanisms related to neuropathic disease are associated with mitochondrial dysfunctions that lead to an activation of the apoptotic cascade. In a model of peripheral neuropathy obtained by the loose ligation of the rat sciatic nerve, acetyl‐L‐Carnitine (ALCAR; 100 mg/kg intraperitoneally [i.p.] twice daily for 14 days) was able to reduce hyperalgesia and apoptosis. In the present study, different mechanisms for the analgesic and the antineuropathic effect of ALCAR are described. The muscarinic blocker atropine (5 mg/kg i.p.) injected simultaneously with ALCAR did not antagonize the ALCAR antihyperalgesic effect on the paw‐pressure test but significantly reduced the analgesic effect of ALCAR. Conversely, the antineuropathic effect of ALCAR was prevented by cotreatment with the nicotinic antagonist mecamylamine (2 mg/kg i.p. twice daily for 14 days). A pharmacological silencing of the nicotinic receptors significantly reduced the X‐linked inhibitor of apoptosis protein–related protective effect of ALCAR on the apoptosis induced by ligation of the sciatic nerve. Taken together, these data highlight the relevance of nicotinic modulation in neuropathy treatment. © 2008 Wiley‐Liss, Inc.
Pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage: Putative mechanisms and novel approaches
Authors: Kolias Angelos G. , Sen Jon , Belli Antonio
Published: August 2008

Cerebral vasospasm is a potentially incapacitating or lethal complication in patients with aneurysmal subarachnoid hemorrhage (SAH). The development of effective preventative and therapeutic interventions has been largely hindered by the fact that the underlying pathogenic mechanisms of cerebral vasospasm remain poorly understood. However, intensive research during the last 3 decades has identified certain mechanisms that possibly play a role in its development. Experimental data suggest that calcium‐dependent and ‐independent vasoconstriction is taking place during vasospasm. It appears that the breakdown products of blood in the subarachnoid space are involved, through direct and/or indirect pathways, in the development of vasospasm after SAH. Free radicals reactions, an imbalance between vasoconstrictor and vasodilator substances (endothelium derived substances, e.g., nitric oxide, endothelin; arachidonic acid metabolites, e.g., prostaglandins, prostacyclin), inflammatory processes, an upheaval of neuronal mechanisms that regulate vascular tone, endothelial proliferation, and apoptosis have all been put forward as causative and/or pathogenic factors. Translational research in the field of vasospasm has traditionally aimed to identify agents/interventions in order to block the cascades initiated after SAH. The combination of novel approaches such as cerebral microdialysis, magnetic resonance spectroscopy, proteomics, and lipidomics could serve a dual purpose: elucidating the complex pathobiochemistry of vasospasm and providing clinicians with tools for early detection of this feared complication. The purpose of this Mini‐Review is to provide an overview of the pathogenesis of cerebral vasospasm and of novel approaches used in basic and translational research. © 2008 Wiley‐Liss, Inc.
A study of the effect of JB particles on Saccharomyces cerevisiae (yeast) cells by Raman spectroscopy
Authors: Bhowmick T. K. , Pyrgiotakis G. , Finton K. , Suresh A. K. , Kane S. G. , Moudgil B. , Bellare Jayesh R.
Published: August 2008

The mechanism of interaction of particulate matter with living system is not completely understood. Evaluation of the effect of particulate Indian traditional medicine JB(JB) on Saccharomyces cerevisiae (yeast) cells is the major focus of the present study. In India, JB is considered as a rejuvenating medicine and used for the treatment of diseases such as diabetes and age‐related eye diseases, as well as a health promoting tonic by the traditional practitioners. In presence of JB, higher growth has been observed at the late stationary growth phase of yeast. Ultra‐structure analysis using transmission electron microscopy (TEM) has shown that JB‐treated yeast cells have better morphology over control in the late stationary growth phase. In this investigation, cellular response from yeast cells after interaction with JB particles was measured using Raman spectroscopy. Raman spectroscopy—a noninvasive tool to distinguish between particle‐treated and untreated cells—revealed that treatment with JB is able to slow the degradation of cellular components (e.g. DNA, proteins and lipids) with the aging of yeast cells. Copyright © 2008 John Wiley & Sons, Ltd.
In situ nucleation and growth of silver nanoparticles in membrane materials: a controllable roughened SERS substrate with high reproducibility
Authors: Zhou Ji , Xu Shuping , Xu Weiqing , Zhao Bing , Ozaki Yukihiro
Published: August 2008

A controllable roughened silver surface with high surface‐enhanced Raman scattering (SERS) activity and high reproducibility has been developed in this study. This silver surface was prepared by silver nucleation in polyelectrolyte multilayers (PEMs) and silver‐enlarged growth. First, the small Ag nuclei were synthesized by NaBH4 in situ reduction of Ag ions on a surface of PEMs. Then the small Ag nuclei formed were effectively enlarged by using a mixture of commercially available reagents named Li Silver. The optical properties and morphologies of the silver substrates have been investigated by ultraviolet–visible (UV–vis) spectroscopy and atomic force microscopy (AFM). The UV–vis and AFM results revealed that the small Ag nuclei separately appeared on the PEMs after NaBH4 in situ reduction. The size of the enlarged Ag nanoparticles can be easily controlled with the immersing cycle in Li Silver. 4‐Mercaptopyridine (4‐MPY) and Rhodamine 6G (R6G) have been used as Raman probes to evaluate the properties of the new SERS substrates. It has been found that the enhancement factor of R6G reached ∼109 after treatment in Li Silver. Reproducibility has been investigated using the SERS signal intensity at 1094 cm−1 of 4‐MPY. Signals collected over multiple spots within the same substrate resulted in a relative standard deviation (RSD) of 6.38%, while an RSD of 10.33% was measured in signals collected from different substrates. Copyright © 2008 John Wiley & Sons, Ltd.
Raman spectroscopic study of the uranyl tellurite mineral moctezumite PbUO2(TeO3)2
Authors: Frost Ray L. , Čejka Jiří , Dickfos Marilla J.
Published: August 2008

The uranyl tellurite mineral moctezumite, Pb(UO2)(TeO3)2, was studied by Raman spectroscopy and complemented with infrared spectroscopy. The presence of the stretching and bending vibrations of uranyl (UO2)2+ and tellurite (TeO3)2− ions was inferred, and the observed bands were assigned to uranyl and tellurite units vibrations. UO bond lengths calculated from the spectra with two empirical relations are close to those inferred from the X‐ray single‐crystal structure of moctezumite. Copyright © 2008 John Wiley & Sons, Ltd.
Electron–phonon coupling and vibrational modes contributing to linear electro‐optic effect of the efficient NLO chromophore 4‐(N,N‐dimethylamino)‐N‐methyl‐4′‐toluene sulfonate (DAST) from their vibrational spectra
Authors: Vijayakumar T. , Hubert Joe I. , Reghunadhan Nair C. P. , Jazbinsek Mojca , Jayakumar V. S.
Published: August 2008

The optimized geometry and structural features of the most prospective electro‐optic crystal 4‐(N,N‐dimethylamino)‐N‐methyl‐4′‐toluene sulfonate (DAST), and the vibrational spectral investigations have been comprehensively described with the near infrared Fourier transform (NIR FT) Raman and Fourier transform infrared (FT‐IR) spectra supported by the density functional theoretical (DFT) computations to elucidate the contribution of vibrational modes to the linear electro‐optic (LEO) effect. Mulliken population analysis and natural bond orbital (NBO) analysis have also been carried out to analyze the effects of intramolecular charge transfer (ICT), intramolecular hydrogen bonding and hyperconjugative interactions on the geometries. The influence of CT interaction between the phenyl ring and the dimethylamino group of the nonlinear optical (NLO) chromophore on the endocyclic and exocyclic angles, and the electronic effects such as hyperconjugation and back‐donation on the methyl hydrogen atoms have been examined. The concurrent intense activation of Raman and IR activities of the effective conjugation vibrational coordinate, which significantly contributes to the LEO effect resulting from the strong electron–phonon (e/ph) coupling, has been analyzed in detail. The effects of frontier orbitals, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), transition of electron density (ED) transfer and the influence of planarity in the stilbazolium ring on the first hyperpolarizability are also discussed. Copyright © 2008 John Wiley & Sons, Ltd.
Raman spectroscopic study of the uranyl selenite mineral demesmaekerite Pb2Cu5(UO2)2(SeO3)6(OH)6·2H2O
Authors: Frost Ray L. , Čejka Jiří , Dickfos Marilla J.
Published: August 2008

The Raman spectrum of the uranyl selenite mineral demesmaekerite was studied, complemented by the infrared spectrum and tentatively interpreted. The observed bands were attributed to the stretching and bending vibrations of (UO2)2+, (SeO3)2− and OH groupings. UO bond lengths in uranyl and OH···O hydrogen bond lengths were calculated from Raman and/or infrared spectra and compared with published data. Copyright © 2008 John Wiley & Sons, Ltd.
A safe and effective method to implant a totally implantable access port in patients with synchronous bilateral mastectomies: Modified femoral vein approach
Authors: Chen Shih‐Yi , Lin Chien‐Hua , Chang Hao‐Ming , Hsu Huan‐Ming , Yu Jyh‐Cherng
Published: August 2008

Background

The purpose of this study was to develop a modified method to implant a totally implantable access port (TIAP) using the femoral vein approach.

Methods

We designed a modified method using the femoral vein approach to implant a TIAP in patients with synchronous bilateral breast cancer requiring bilateral mastectomy and postoperative chemotherapy. TIAP implantation was performed with parenteral sedation and local anesthesia in the operating room. All patients were followed for at least 12 months and the complications of TIAP were recorded.

Results

In this retrospective study, 86 patients received the TIAP using the modified femoral vein approach. All patients had a history of bilateral breast cancer and underwent bilateral mastectomy. The early complication rate within the first 30 postoperative days was 2.3% and involved groin hematoma caused by missed puncture to the femoral artery during the operation. The late postoperative complication rates were 2.3% caused by local port infection, 1.2% by groin wound infection, and 3.5% by catheter occlusion. There were no complications associated with TIAP disconnection or systemic infection.

Conclusion

Traditional implantation of TIAP through the subclavian vein or cephalic vein is simple and is used worldwide. However, both the percutaneous puncture and cutdown methods have limitations and risks. We describe a safe and effective method using the modified femoral vein approach for specific patients. J. Surg. Oncol. 2008;98:?–?. © 2008 Wiley‐Liss, Inc.
CZE separation of strawberry anthocyanins with acidic buffer and comparison with HPLC
Authors: Comandini Patrizia , Blanda Giampaolo , Cardinali Andrea , Cerretani Lorenzo , Bendini Alessandra , Caboni Maria Fiorenza
Published: August 2008

Anthocyanins, the major colourants of strawberries, are polar pigments that are positively charged at low pH. Herein, we have assessed a new analytical method for the separation of anthocyanins using CZE. Acidic buffer solutions (pH <2) were employed in order to maintain pigments in the cation flavylium form and achieve high molar absorptivity at 510 nm. These spectral properties enabled us to identify strawberry anthocyanins in a preliminary stage by detection in the visible range, although the method was optimised at 280 nm to obtain the best S/N. The effects of buffer composition highlighted the necessity of adding an organic modifier to the running buffer to obtain a suitable separation. The electrophoretic method permitted the separation of the three main anthocyanins of strawberry extracts, namely pelargonidin 3‐glucoside (Pg‐glu), pelargonidin 3‐rutinoside and cyanidin 3‐glucoside. The electrophoretic results, expressed as retention time and separation efficiency of the major anthocyanin (Pg‐glu), were compared to those achieved in HPLC, the analytical technique traditionally used for the investigation of anthocyanins in vegetable matrix. The content of Pg‐glu in strawberries (cv. Camarosa), calculated with HPCE and HPLC methods, resulted respectively in 11.41 mg/L and 11.37 mg/L.
Fast, noninvasive and simultaneous near‐infrared spectroscopic characterisation of physicochemical stationary phases' properties: From silica particles towards monoliths
Authors: Petter Christine H. , Heigl Nico , Bonn Günther K. , Huck Christian W.
Published: August 2008

The design of novel stationary phases is a permanent demanding challenge in chromatographic separation science to enable analysis with enhanced selectivity, specificity and speed. Therefore, the characterisation of chemical and physical properties is next to calculation of chromatographic parameters essential. Conventionally, chemical parameters including surface coverage are determined by burning combustion or frontal analysis, physical parameters including particle size, pore size, pore volume and surface area are determined by SEM, mercury intrusion porosimetry (MIP) and Brunauer–Emmett–Teller (BET). All these methods are time consuming, invasive and require besides special equipment some special trained laboratory staff. Therefore, we introduced near‐infrared spectroscopy (NIRS) as a noninvasive, easy‐to‐handle technology with wavenumber ranging from 4000 to 10 000 cm–1 enabling analysis within only a few seconds at higher precision than the conventional methods. Investigated materials comprise porous and nonporous silica gel, carbon‐based nanomaterials (fullerenes), polymer beads and monoliths. Different carriers themselves and their kind of derivatisations (RP, normal‐phase, ion‐exchanger, IMAC (immobilised metal affinity chromatography), affinity) can be determined by applying principal component analysis (PCA) of recorded spectra. Partial least square regression (PLSR) enables the determination of particle size, pore size, pore volume, porosity, total porosity and surface area with one single measurement. For the optimised design of well‐defined polymer beads and monoliths, real‐time in situ monitoring to control, e. g. particle and pore sizes as well as monomer content during the polymerisation process, can be extremely helpful. In this article, the advantages of this fast, noninvasive high‐throughput NIRS methods are summarised, discussed in detail and different applications of the individual characterised materials are shown.
Coupling of ionic liquid‐based headspace single‐drop microextraction with GC for sensitive detection of phenols
Authors: Zhao Fa‐Qiong , Li Jing , Zeng Bai‐Zhao
Published: August 2008

A headspace single‐drop microextraction (SDME) based on ionic liquid (IL) has been developed for the gas chromatographic determination of phenols. The volume of IL microdrop used was 1 μL. After extraction, the analytes were desorbed from the drop in the injection port and the involatile IL was withdrawn into the microsyringe. To facilitate the withdrawal of IL the upper diameter of the split inlet liner was enlarged to some extent. Some parameters were optimized for the determination of phenols. Under the selected conditions, i.e., desorption for 100 s at 210°C after extraction for 25 min at 50°C in solutions (pH 3) containing 0.36 g/mL sodium chloride, the LODs, RSDs, and the average enrichment factors of phenols were 0.1–0.4 ng/mL, 3.6–9.5% (n = 5), and 35–794, respectively. The proposed procedure was applied to the determination of phenols in lake water and wastewater samples, and the spiked recoveries were in the range of 81–111% at a spiked level of 0.4 μg/mL. This method is a promising alternative for the sensitive determination of phenolic compounds.
Enantioselective determination of chloroquine and its n‐dealkylated metabolites in plasma using liquid‐phase microextraction and LC‐MS
Authors: dos Santos Magalhães Igor Rafael , Sueli Bonato Pierina
Published: August 2008

A selective method using three‐phase liquid‐phase microextraction (LPME) in conjunction with LC‐MS‐MS was devised for the enantioselective determination of chloroquine and its n‐dealkylated metabolites in plasma samples. After alkalinization of the samples, the analytes were extracted into n‐octanol immobilized in the pores of a polypropylene hollow fiber membrane and back extracted into the acidic acceptor phase (0.1 M TFA) filled into the lumen of the hollow fiber. Following LPME, the analytes were resolved on a Chirobiotic V column using methanol/ACN/glacial acetic acid/diethylamine (90:10:0.5:0.5 by volume) as the mobile phase. The MS detection was carried out using multiple reaction monitoring with ESI in the positive ion mode. The optimized LPME method yielded extraction recoveries ranging from 28 to 66%. The method was linear over 5–500 ng/mL and precision (RSD) and accuracy (relative error) values were below 15% for all analytes. The developed method was applied to the determination of the analytes in rat plasma samples after oral administration of the racemic drug.
Allocating the value of an open‐loop optimal control problem between its state variables
Authors: Pierru Axel , Gaumont Damien
Published: August 2008

A new theorem is proposed for allocating the value of an open‐loop optimal control problem over the planning period between its various state variables. Potential applications in economics and management are suggested. Copyright © 2008 John Wiley & Sons, Ltd.
In situ localisation and quantification of surfactins in a Bacillus subtilis swarming community by imaging mass spectrometry
Authors: Debois Delphine , Hamze Kassem , Guérineau Vincent , Le Caër Jean‐Pierre , Holland I. Barry , Lopes Philippe , Ouazzani Jamal , Séror Simone J. , Brunelle Alain , Laprévote Olivier
Published: August 2008

Surfactins are a family of heptacyclopeptides in which the C‐terminal carbonyl is linked with the β‐hydroxy group of a fatty acid acylating the N‐terminal function of a glutamic acid residue. The fatty acyl chain is 12–16 carbon atoms long. These compounds, which are secreted by the Gram‐positive bacterium Bacillus subtilis in stationary phase in liquid cultures, play an important role in swarming communities on the surface of agar media in the formation of dendritic patterns. TOF secondary ion MS (TOF‐SIMS) imaging was used to map surfactins within 16–17 h swarming patterns, with a 2 μm spatial resolution. Surfactins were mainly located in the central mother colony (the site of initial inoculation), in a ‘ring’ surrounding the pattern and along the edges of the dendrites. In the mother colony and the interior of the dendrites, surfactins with shorter chain lengths are present, whereas in the ring surrounding the swarm community and between dendrites, surfactins with longer fatty acyl chain lengths were found. A quantitative analysis by MALDI‐TOF MS showed a concentration gradient of surfactin from the mother colony to the periphery. The concentration of surfactin was ∼400 pmol/mL in the mother colony and ∼10 pmol/mL at the base of the dendrites, decreasing to 2 pmol/mL at their tips.