bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Evidence of Placental Hypoxia in Preeclampsia
Authors: Soleymanlou Nima , Jurisica Igor , Nevo Ori , Ietta Francesca , Zhang Xin , Zamudio Stacy , Post Martin , Caniggia Isabella 
Published: July 2005

Abstract
Background: Oxygen plays a central role in human placental pathologies including preeclampsia, a leading cause of fetal and maternal death and morbidity. Insufficient uteroplacental oxygenation in preeclampsia is believed to be responsible for the molecular events leading to the clinical manifestations of this disease.
Design: Using high-throughput functional genomics, we determined the global gene expression profiles of placentae from high altitude pregnancies, a natural in vivo model of chronic hypoxia, as well as that of first-trimester explants under 3 and 20% oxygen, an in vitro organ culture model. We next compared the genomic profile from these two models with that obtained from pregnancies complicated by preeclampsia. Microarray data were analyzed using the binary tree-structured vector quantization algorithm, which generates global gene expression maps.
Results: Our results highlight a striking global gene expression similarity between 3% O2-treated explants, high-altitude placentae, and importantly placentae from preeclamptic pregnancies. We demonstrate herein the utility of explant culture and high-altitude placenta as biologically relevant and powerful models for studying the oxygen-mediated events in preeclampsia.
Conclusion: Our results provide molecular evidence that aberrant global placental gene expression changes in preeclampsia may be due to reduced oxygenation and that these events can successfully be mimicked by in vivo and in vitro models of placental hypoxia.
Severe Growth Hormone Insensitivity Resulting from Total Absence of Signal Transducer and Activator of Transcription 5b
Authors: Hwa Vivian , Little Brian , Adiyaman Pelin , Kofoed Eric M. , Pratt Katherine L. , Ocal Gonul , Berberoglu Merih , Rosenfeld Ron G. 
Published: July 2005

Abstract
Context: The central clinical feature of GH insensitivity (GHI) is severe growth failure associated with elevated serum concentrations of GH and abnormally low serum levels of IGF-I. GHI can be the result of an abnormality in the GH receptor or aberrancies downstream of the GH receptor.
Objective: We investigated the GH-IGF-I axis in a young female GHI subject who presented with a height of 114 cm (−7.8 sd score) at age 16.4 yr.
Patient: The subject, from a consanguineous pedigree, had circulating levels of GH and GH-binding protein that were normal to elevated, whereas IGF-I (7.2 ng/ml; normal, 242–600), IGF-binding protein-3 (543 ng/ml; normal, 2500–4800), and acid-labile subunit (1.22 μg/ml; normal, 5.6–16) levels were abnormally low and failed to increase during an IGF-I generation test.
Design: Dermal fibroblast cultures were established with the consent of the patient and family. Immunoblot analysis of cell lysates and DNA sequencing of her signal transducer and activator of transcription 5b (STAT5b), a critical intermediate of the GH-IGF-I axis, were performed.
Results: Sequencing of the STAT5b gene revealed a novel homozygous insertion of a single nucleotide in exon 10. The insertion resulted in a frame shift, leading to early protein termination and consequent lack of immunodetectable STAT5b protein.
Conclusion: The identification of a second case of severe growth failure associated with STAT5b mutation implicates a unique and critical role for STAT5b in GH stimulation of IGF-I gene expression and statural growth.
Approximative kinetic formats used in metabolic network modeling
Authors: Heijnen Joseph J. 
Published: July 2005

AbstractAn overview is presented of the different approximative enzyme kinetic formats that have been proposed for use in metabolic modeling studies. It is considered that the following four general properties are relevant for approximative kinetics: the rate must be proportional to enzyme level; at high metabolite concentrations, there is downward concave behavior of rate versus concentration; the number of kinetic parameters should be as small as possible; analytical solutions of steady‐state network balances are desirable. Six different approximative kinetic formats are evaluated (linear, logarithmic‐linear, power law GMA, power law S‐systems, thermokinetic, linear‐logarithmic) and it is concluded that only the recently proposed linear‐logarithmic approach combines all desired properties and therefore seems a most appropriate approximate kinetic format. © 2005 Wiley Periodicals, Inc.
Rheology, Sedimentation, and Filtration of TiO2 Suspensions
Authors: Gesenhues U. 
Published: July 2005

AbstractIt is shown that with aqueous suspensions of colloidal oxide and hydroxide particles simple rheometric and sedimentation experiments allow the determination of the optimum pH for filtration and washing. This approach is more practical than zeta potential measurements, as explained by a theoretical review and illustrated by experiments with industrial TiO2 white pigments of varying surface chemistry. Besides, the solids content of the filter cake and its dependence on pH is correctly predicted from the rheology of the suspension, thus giving an idea of the mechanism of filter cake formation. This follows from a comparison to the results of filtration experiments. There, the influences of filter vacuum as well as of pH and solids content of the pigment feed suspension on filtration capacity and washing efficiency have been studied. The experiments also illustrate an inexpensive method of how to find the optimum set of parameters for an economical drum filter operation in the plant.
Simulation of Pipeline Slurry Flow under Conditions of Granular Phase Ablation
Authors: Eskin D. , Leonenko Y. , Vinogradov O. 
Published: July 2005

AbstractA model of granular flow in the regime of a moving bed under conditions of granular phase ablation is developed. The model is based on the well‐known two‐layer representation of stratified slurry flow, which assumes a dynamic equilibrium between the bottom (granular) layer and the upper layer of solids‐liquid suspension. The mass transfer rate from the bottom layer to the upper one is defined on the basis of digestion model for a single spherical lump. The model developed allows estimation of the lengths required for the total digestion of lumps in a moving bed and the axial pressure gradient distribution for different flow regimes.
The Barton Reaction: Can a More Tenable Pathway Be Hypothesized for the Formation of Nitrosoalkyl Derivatives?
Authors: Grossi Loris 
Published: July 2005

AbstractHerein, we report that in the formation of nitrosoalkyl derivatives during the photolysis of alkyl nitrites, the formation of the intermediate alkyl alkoxy nitroxide, due to the trapping of alkyl radicals by the starting nitrite, is the key step of the entire process. In fact, these nitroxides, detectable by EPR spectroscopy, decay to the final nitroso derivatives under thermodynamic control. In light of this, the Barton reaction mechanism has been reviewed. The nitrosoalkyl derivatives, or the hydroxamic acids when steroids are involved, have now to be considered as the ending products of the entire process and not, unless a very high concentration of NO is present in the medium, the result of a direct reaction of NO with the alkyl radical, as is commonly accepted.
A potential role for β‐ and γ‐crystallins in the vascular remodeling of the eye
Authors: Zhang Cheng , Gehlbach Peter , Gongora Celine , Cano Marisol , Fariss Robert , Hose Stacey , Nath Avindra , Green William R. , Goldberg Morton F. , Zigler J. Samuel , Sinha Debasish 
Published: July 2005

AbstractWe demonstrate that expression of β‐ and γ‐crystallins is associated with intraocular vessels during normal vascular development of the eye and also in the Nuc1 rat, a mutant in which the hyaloid vascular system fails to regress normally. Real‐Time RT PCR, Western blot and metabolic labeling studies indicate an increased expression of β‐ and γ‐crystallins in Nuc1 retina. The increased expression of crystallins was localized to the astrocytes surrounding the intraocular vessels. A similar pattern of crystallin expression was also observed in the retinal vessels during normal development. Cultured human astrocytes exposed to 3‐nitropropionic acid, an established model of neuronal hypoxia, increased VEGF expression, as expected, but also increased expression of crystallins. Our data suggest that crystallins may function together with VEGF during vascular remodeling. Interestingly, in human PFV (persistent fetal vasculature) disease, where the hyaloid vasculature abnormally persists after birth, we show that astrocytes express both VEGF and crystallins. Developmental Dynamics 234:36–47, 2005. © 2005 Wiley‐Liss, Inc.
Heterogeneous expression of GAGE, NY‐ESO‐1, MAGE‐A and SSX proteins in esophageal cancer: Implications for immunotherapy
Authors: Akcakanat Argun , Kanda Tatsuo , Tanabe Tadashi , Komukai Shintarou , Yajima Kazuhito , Nakagawa Satoru , Ohashi Manabu , Hatakeyama Katsuyoshi 
Published: July 2005

AbstractCancer/testis antigens (CTAs) elicit immune response in cancer patients and are therefore targets of immunotherapy. Current information on CTA expression is primarily based on mRNA assays and little is known about their expression at the protein level. The objectives of our study are to analyze GAGE, NY‐ESO‐1, MAGE‐A and SSX protein expression in esophageal cancer and to correlate their expression patterns with clinicopathologic parameters and survival. We examined CTA protein expression in 213 patients with esophageal cancer by immunohistochemistry. Antigen‐positive tumors were evaluated once and antigen‐negative tumors were evaluated 3 times by examining different parts of the cancer specimen. GAGE, NY‐ESO‐1 and MAGE‐A were heterogeneously expressed in 42 (20%), 44 (21%) and 111 (52%) tumors, respectively, whereas SSX expression was not detected. Of the 126 (59%) patients expressing CTAs, 70 (33%) expressed 1, 41 (19%) expressed 2 and 15 (7%) expressed 3 antigens. The expression of MAGE‐A was correlated with those of GAGE (p=0.001) and NY‐ESO‐1 (p=0.002), and the expression of GAGE was correlated with that of NY‐ESO‐1 (p=0.002). One hundred fifty‐six (79%) sections were positively stained in the first evaluation, whereas 37 (19%) and 4 (2%) positive sections were identified in the second and third evaluations, respectively. Particularly, MAGE and GAGE expression showed overlaps. GAGE, NY‐ESO‐1 and MAGE‐A protein expression was not correlated with the disease progression, TNM factors or survival. The detection of immunonegative cells in every specimen suggests addition of other drugs such as 5‐aza‐2′‐deoxycytidine to increase the therapeutic effect of CTA‐specific cancer vaccines. © 2005 Wiley‐Liss, Inc.
Efficacy of the MMP inhibitor MMI270 against lung metastasis following removal of orthotopically transplanted human colon cancer in rat
Authors: Ogata Yutaka , Matono Keiko , Nakajima Motowo , Sasatomi Teruo , Mizobe Tomoaki , Nagase Hideaki , Shirouzu Kazuo 
Published: July 2005

AbstractWe have investigated the antitumor effects of synthetic MMP inhibitor MMI270 against postoperative lung metastasis from colon cancer in nude rat. The KM12SM human colon cancer cells were injected into the cecal wall, and at 5 weeks after the injection, the cecum was removed including the tumor. Then, 30 mg/kg of MMI270 was administered perorally twice per day for 2 or 4 weeks, either immediately after removal or after week 2 after the removal. At week 7 after the removal, lung metastasis was significantly inhibited by the early administration of MMI270 immediately after the tumor removal but not by the late administration. The survival rates were significantly higher in the rats treated by early administration of MMI270 compared to the survival rate in untreated rats. Moreover, no lung metastasis was detected in some rats with 24‐weeks' survival treated by early administration. Lower microvessel density, lower PCNA Index and higher Apoptotic Index in the lung metastases of the rats treated with MMI270 were found compared to those in untreated rats. A beneficial effect of by early administration of MMI270 against postoperative lung metastases may be expected through inhibiting neovascularization of metastases in nude rat. © 2005 Wiley‐Liss, Inc.
Enhanced cytotoxicity induced by gefitinib and specific inhibitors of the Ras or phosphatidyl inositol‐3 kinase pathways in non‐small cell lung cancer cells
Authors: Janmaat Maarten L. , Rodriguez José A. , Gallegos‐Ruiz Mariëlle , Kruyt Frank A.E. , Giaccone Giuseppe 
Published: July 2005

AbstractIn this study, we have characterized a panel of NSCLC cell lines with differential sensitivity to gefitinib for activating mutations in egfr, pik3ca, and k‐ras, and basal protein expression levels of PTEN. The egfr mutant NSCLC cell line H1650 as well as the egfr wild type cell lines H292 and A431 were highly sensitive to gefitinib treatment, indicating that other factors determine gefitinib‐sensitivity in egfr wild type cells. Activating k‐ras mutations were specifically detected in gefitinib‐resistant cells, suggesting that the occurrence of k‐ras mutations is correlated with resistance to EGFR antagonists. No pik3ca mutations were detected within the panel of cell lines, and PTEN protein expression levels did not correlate with gefitinib sensitivity. Gefitinib effectively blocked Akt and Erk phosphorylation in two gefitinib‐sensitive NSCLC cell lines, further supporting our previous findings that persistent activity of the PI3K/Akt and/or Ras/Erk pathways is associated with gefitinib‐resistance of NSCLC cell lines. Gefitinib‐resistant NSCLC cell lines, showing EGFR‐independent activity of the PI3K/Akt or Ras/Erk pathways, were treated with gefitinib in combination with specific inhibitors of mTOR, P13K, Ras, and MEK. Additive cytotoxicity was observed in A549 cells co‐treated with gefitinib and the MEK inhibitor U0126 or the farnesyl transferase inhibitor SCH66336 and in H460 cells treated with gefitinib and the PI3K inhibitor LY294002, but not in H460 cells treated with gefitinib and rapamycin. These data suggest that combination treatment of NSCLC cells with gefitinib and specific inhibitors of the PI3K/Akt and Ras/Erk pathways may provide a successful strategy. © 2005 Wiley‐Liss, Inc.
EGFR and erbB2 mutation status in Japanese lung cancer patients
Authors: Sasaki Hidefumi , Shimizu Shigeki , Endo Katsuhiko , Takada Minoru , Kawahara Masaaki , Tanaka Hisaichi , Matsumura Akihide , Iuchi Keiji , Haneda Hiroshi , Suzuki Eriko , Kobayashi Yoshihiro , Yano Motoki , Fujii Yoshitaka 
Published: July 2005

AbstractMuch evidence has accumulated that the epidermal growth factor receptor (EGFR) and its family members are strongly implicated in the development and progression of lung cancers. Somatic mutations of the EGFR gene were found in about 25–40% of Japanese lung cancer patients. More recently, erbB2 mutations are found in about 4% of European‐derived lung cancer patients. We have investigated EGFR and erbB2 mutation status in 95 surgically treated nonsmall cell lung cancer (NSCLC) cases from Nagoya City University Hospital. Seventy‐five adenocarcinoma cases were included. The presence or absence of EGFR and ernB2 mutations of kinase domains were analyzed by reverse transcription polymerase chain reaction (RT‐PCR) amplifications and direct sequences. We have also investigated erbB2 mutation status in 27 surgically treated NSCLC cases followed by treatment with gefitinib from Kinki‐chuo Chest Medical Center. EGFR mutations (CTG→CGG; L858R) were found from 14 of 95 lung cancer patients. We also detected the deletion 1a‐type mutations from 9 patients and deletion 4‐type mutations from 6 patients in exon 19. In exon 20, 4 mutations including 2 novel mutations were found. Total EGFR mutations were present in 35 patients (36.8%). These mutation statuses were significantly correlated with gender (women 73.3% vs. men 20%, p < 0.0001), smoking status (never smoker 69.4% vs. smoker 16.9%, p < 0.0001), pathologic subtypes (adenocarcinoma 45.1% vs. nonadenocarcinoma 12.5%, p = 0.0089) and differentiation status of the lung cancers (well 51% vs. moderately or poorly 18.4%, p = 0.0021). On the other hand, erbB2 mutation was only found from 1 of 95 patients, at exon 20. This patient was female and a never smoker with adenocarcinoma. This 12 nucleotide insertion mutation (2324–2325 ins ATACGTGATGGC) was located in the exon 20 at kinase domain (775–776 ins YVMA). There was no erbB2 mutation in 27 gefitinib‐treated NSCLC patients. In total, we have found only 1 erbB2 mutation from 122 (0.8%) Japanese NSCLC patients. There was a significantly higher erbB2 positive (2+/3+) ratio in EGFR mutant patients (13/25, 52.0%) compared to EGFR wild‐type patients (10/62, 16.1%; p = 0.0247). The NSCLC specimen with erbB2 mutation showed 1+ immunoreactivity. The EGFR mutation status might correlate with the clinicopathologic features related to good response to gefitinib, such as gender, smoking history and pathologic subtypes of lung cancers. However, erbB2 mutation is rare from Japanese lung cancer and is of limited value for molecular target therapy. © 2005 Wiley‐Liss, Inc.
Betulinic acid, a natural cytotoxic agent, fails to trigger apoptosis in human Burkitt's lymphoma‐derived B‐cell lines
Authors: Karpova Maria B. , Sanmun Duangmanee , Henter Jan‐Inge , Smirnov Aleksandr F. , Fadeel Bengt 
Published: July 2005

AbstractBetulinic acid (BA), a pentacyclic triterpene of natural origin, effectively induces apoptosis in neuroectodermal tumors and was recently shown to be a potent trigger of cell death in human leukemia‐derived cell lines. To explore the potential of BA in the treatment of hematologic malignancies, we tested a panel of 10 Burkitt's lymphoma (BL)‐derived B‐cell lines for sensitivity to BA. The human Jurkat T leukemia cell line was included as a positive control. Our studies show that BA exerts cytotoxic effects in some of the BL cell lines tested, including DG75, a chemoresistant BL cell line. However, cell death was caspase‐independent, as evidenced by a lack of protection by zVAD‐fmk, a pancaspase inhibitor, and displayed signs of necrosis. Furthermore, BA‐induced caspase activation was seen to a minor extent in only 1 of the 10 BL cell lines tested (Ramos, a p53‐deficient cell line), but was readily detected in Jurkat cells. Together, these studies indicate that resistance to BA‐induced apoptosis is a common feature of BL‐derived cell lines. © 2005 Wiley‐Liss, Inc.
Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation
Authors: Seliger Barbara , Ritz Ulrike , Soldano Ferrone 
Published: July 2005

AbstractIn humans as in other animal species, CD8+cytotoxic T lymphocytes (CTLs) play an important if not the major role in controlling virus‐infected and malignant cell growth. The interactions between CD8+T cells and target cells are mediated by human leukocyte antigen (HLA) class I antigens loaded with viral and tumor antigen‐derived peptides along with costimulatory receptor/ligand stimuli. Thus, to escape from CD8+T‐cell recognition and destruction, viruses and tumor cells have developed strategies to inhibit the expression and/or function of HLA class I antigens. In contrast, cells with downregulated MHC class I surface expression can be recognized by NK cells, although NK cell‐mediated lysis could be abrogated by the expression of inhibiting NK cell receptors. This review discusses the molecular mechanisms utilized by viruses to inhibit the formation, transport and/or expression of HLA class I antigen/peptide complexes on the cell surface. The knowledge about viral interference with MHC class I antigen presentation is not only crucial to understand the pathogenesis of viral diseases, but contributes also to the design of novel strategies to counteract the escape mechanisms utilized by viruses. These investigations may eventually lead to the development of effective immunotherapies to control viral infections and virus‐associated malignant diseases. © 2005 Wiley‐Liss, Inc.
Bioadhesive Properties of a Polyaminoacidic Hydrogel: Evaluation by ATR FT‐IR Spectroscopy
Authors: Saiano Filippo , Pitarresi Giovanna , Mandracchia Delia , Giammona Gaetano 
Published: July 2005

AbstractSummary: The bioadhesive properties of a novel chemical hydrogel based on a polymer of protein‐like structure, have been investigated by using ATR FT‐IR spectroscopy. In particular, the copolymer PHG obtained by partial derivatization of PHEA with GMA was chemically crosslinked by UV irradiation at 313 nm. Crosslinked PHG was treated with water to obtain a swelled sample, named PHG‐UV gel, that was brought into contact with a phosphate buffer/citric acid solution at pH 7.0 in the absence or in the presence of mucin at various concentrations (0.01, 0.1 and 1 wt.‐%). Preliminary dynamic swelling studies have evidenced the occurrence of an interaction between the PHG‐UV gel and the glycoprotein. This result was confirmed by ATR FT‐IR measurements. A diffusion model using a solution of Ficks' second law was employed to determine the diffusion coefficient of water into PHG‐UV gel as a consequence of adsorption and/or interdiffusion which occur at the PHG‐UV gel/mucin solution interface. Experimental results suggest a potential use of PHG‐UV gel to prepare bioadhesive devices.
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Targeting NAD(P)H:quinone oxidoreductase (NQO1) in pancreatic cancer
Authors: Lewis Anne M. , Ough Matthew , Hinkhouse Marilyn M. , Tsao Ming‐Sound , Oberley Larry W. , Cullen Joseph J. 
Published: July 2005

AbstractNAD(P)H:quinone oxidoreductase (NQO1) functions as an important part of cellular antioxidant defense by detoxifying quinones, thus preventing the formation of reactive oxygen species (ROS). The aim of our study was to determine if NQO1 is elevated in pancreatic cancer specimens and pancreatic cancer cell lines and if so, would compounds previously demonstrated to redox cycle with NQO1 be effective in killing pancreatic cancer cells. Immunohistochemistry of resected pancreatic specimens demonstrated an increased immunoreactivity for NQO1 in pancreatic cancer and pancreatic intraepithelial neoplasia (PanIN) specimens versus normal human pancreas. Immunocytochemistry and Western immunoblots demonstrated increased immunoreactivity in pancreatic cancer cells when compared to a near normal immortalized human pancreatic ductal epithelial cell line and a colonic epithelial cell line. Streptonigrin, a compound known to cause redox cycling in the presence of NQO1, decreased clonogenic survival and decreased anchorage‐independent growth in soft agar. Streptonigrin had little effect on cell lines with absent or reduced levels of NQO1. The effects of streptonigrin were reversed in pancreatic cancer cells pretreated with dicumarol, a known inhibitor of NQO1. NQO1 may be a therapeutic target in pancreatic cancer where survival is measured in months. © 2005 Wiley‐Liss, Inc.
Evidence for motor axon depolarization in Fabry disease
Authors: Tan Stella V. , Lee Philip J. , Walters Richard J. L. , Mehta Atul , Bostock Hugh 
Published: July 2005

AbstractTo investigate the pathophysiology of neuropathy in Fabry disease, multiple nerve excitability properties of median motor axons in 20 patients with this disorder but without hyperkalemia were compared with 35 age‐matched normal controls. In the patients, depolarizing threshold electrotonus was reduced (P < 0.0001) and superexcitability was reduced (P < 0.001), but late subexcitability was normal. These findings indicate that the axons were mildly depolarized, probably due to ischemia, and are consistent with the hypothesis that poor nerve perfusion in Fabry disease contributes to axonal damage. Muscle Nerve, 2005