bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simple and rapid dispersive liquid–liquid microextraction method followed by GC‐FID for determination ofN‐methylpyrrolidine in cefepime
Authors: Farajzadeh Mir Ali , Goushjuii Leila , Bashour Yousef 
Published: October 2010

AbstractA simple, rapid and efficient sample preparation technique, dispersive liquid–liquid microextraction, coupled with gas chromatography‐flame ionization detection has been developed to determineN‐methylpyrrolidine in cefepime. The effect of various experimental factors on the preparation procedure, such as the nature and volume of extraction and disperser solvents, extraction time, the nature of buffer and its pH, and salt effect, was investigated, optimized and the following results were obtained: extraction solvent, chloroform; dispersive solvent and solvent for dissolving cefepime, a mixture of methanol/water (88:12, v/v); salting out agent, NaCl; and buffer, carbonate/bicarbonate (C=0.5 M, pH=12). The optimized conditions were applied to the real sample (cefepime) for the extraction and determination ofN‐methylpyrrolidine. The calibration graph is linear from 0.02 to 850 mg/L with the square of correlation coefficient 0.999. LOD and LOQ are 6.4 and 21.2 μg/L in solution, respectively, and 0.2 (2×10−5) and 0.6 (6×10−5) μg/g (%, w/w) in cefepime powder, respectively, using sample size 50 mg. Repeatability of the method is good and RSD% for six repeated experiments (C=170 mg/L) is 6.35%.
Single‐wall carbon nanotubes assisted photothermal cancer therapy: Animal study with a murine model of squamous cell carcinoma
Authors: Huang Naiyan , Wang Hequn , Zhao Jianhua , Lui Harvey , Korbelik Mladen , Zeng Haishan 
Published: October 2010

AbstractBackground and ObjectivesThere has been a dramatic increase in photothermal therapy as a minimally invasive treatment modality for cancer treatment due to the development of novel nanomaterials as the light absorption agents. Single‐wall carbon nanotubes (SWNTs) with strong optical absorption in the broad visible and near IR offer unique advantages for photothermal cancer therapy. A broad range of wavelengths can be used for the treatment with SWNTs, whereas conventional photothermal therapeutic agent is designed to absorb light only near one selected wavelength. The objective of this study is to validate the hypothesis that intratumoral injected SWNTs can absorb 785 nm near IR laser light and generate significant local hyperthermia to destroy tumors.Study Design/Materials and MethodsSCCVII tumor in C3H/HeN mice was exposed to 785‐nm laser after intratumoral injection of SWNTs with different light and SWNTs dose combinations. The temperatures of the tumor with laser irradiation were monitored. In vivo and ex vivo Raman spectra in different organs were obtained with a rapid Raman system. Tumor responses (tumor volume and mouse survival) were documented daily after treatment up to day 45 to assess the effectiveness of the treatment.ResultsThe temperature within the tumors increased in a light‐ and SWNTs‐dose dependent manner. Squamous cell carcinomas can be eradicated at a moderate light irradiance and fluence (200 mW/cm2 and 120 J/cm2). This light dose is also comparable to those used with photodynamic therapy. Tissue Raman spectroscopy measurements revealed that SWNTs remained localized in the tumor even 3 months after injection but was not found in other organs.ConclusionsThis animal study represents a significant step forward towards the goal of advancing SWNTs based photothermal cancer therapy into clinical applications. Lasers Surg. Med. 42:798–808, 2010 © 2010 Wiley‐Liss, Inc.
A Personalized Approach to Metabolic Aspects of Obesity
Authors: Brietzke Stephen A. 
Published: October 2010

AbstractMetabolic syndrome, which is entwined in semantic controversy as to its actual existence as a distinct entity, links several important health conditions with obesity, and more specifically, excessive visceral adiposity. The most common linked disease states include type 2 diabetes mellitus, hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular and coronary heart disease. Much of the controversy surrounding the metabolic syndrome case definition is the purported centrality of insulin resistance as root cause, there being no universally agreed‐upon standard for measurement of insulin resistance. Over the past decade, the visceral adipocyte itself has emerged as a key contributor rather than passive bystander in the genesis of the metabolic syndrome. Rather than being a simple storage bin for excess triglyceride, the visceral adipocyte is an active endocrine cell secreting a variety of signal hormones known in the aggregate as adipokines. In optimal health, the predominant recognized adipokine is adiponectin, with downstream insulin‐sensitizing, anti‐inflammatory, antithrombotic, provasodilatory effects systemically. By contrast, metabolic syndrome is characterized by reduced adiponectin and increased inflammatory adipokine secretion, with downstream effects of insulin resistance, heightened inflammation, prothrombosis, and vasoconstriction. These alternative metabolic states of the adipocyte are characterized in this review as metabolic “yin” and “yang.” Lifestyle modifications and drug therapies that promote weight loss, increased physical exercise activity, and increased adiponectin production tend to modulate the system favorably toward metabolic “yin.” Mt Sinai J Med 77:499–510, 510, 2010. © 2010 Mount Sinai School of Medicine
Medical Therapy for Obesity
Authors: Bray George A. 
Published: October 2010

AbstractObesity results from a prolonged small positive energy imbalance, and treatment needs to reverse this imbalance. Many different diets have been tried to treat obesity, and weight loss occurs with all of them. There is currently no evidence that supports the superiority of one macronutrient composition for diets over any other. The principal effect seems to be the degree of adherence to the prescribed calorie reduction. Obesity drugs have been developed that tap brain mechanisms for controlling feeding and the gastrointestinal tract and its peptides. Orlistat blocks intestinal lipase and produces modest weight loss. Sibutramine is a serotonin‐norepinephrine reuptake inhibitor that has a warning on its label from the US Food and Drug Administration because of cardiovascular risk. Its marketing has been suspended in Europe. Several drug combinations are on the horizon for treatment of obesity.Mt Sinai J Med 77:407–417, 2010.. © 2010 Mount Sinai School of Medicine
Weight Management in Type 2 Diabetes Mellitus
Authors: Siram Amulya T. , Yanagisawa Robert , Skamagas Maria 
Published: October 2010

AbstractObesity is a well known risk factor for type 2 diabetes mellitus. Individuals with type 2 diabetes mellitus are at risk for weight gain as a result of multiple influences, including sedentary lifestyle, high‐calorie diet, diabetes medications, sociocultural factors, chronic medical and psychiatric illnesses, and a dysregulated enteroendocrine axis. Because both diabetes mellitus and obesity predispose patients to abnormal cardiometabolic profiles and increased cardiovascular disease, management of diabetes mellitus should focus on weight management and optimizing cardiometabolic parameters, concomitant with glycemic control. Lifestyle modification incorporating healthy, calorie‐appropriate diets and increased physical activity, in addition to metformin, are central components to diabetes management and weight management. These interventions have been shown to improve body weight, glycemic control, and overall cardiometabolic profile. The weight‐neutral and weight‐losing diabetes medications include metformin, alpha‐glucosidase inhibitors, glucagon‐like peptide‐1 analogs, dipeptidyl peptidase‐4 inhibitors, and amylin analogs. It is essential that providers understand the metabolic and weight effects of diabetes medications in order to develop strategies for managing diabetes mellitus while helping patients maintain or lose weight in order to improve their overall health outcomes. Mt Sinai J Med 77:533–548,2010. © 2010 Mount Sinai School of Medicine
miRNAs in human cancer
Authors: Farazi Thalia A , Spitzer Jessica I , Morozov Pavel , Tuschl Thomas 
Published: October 2010

AbstractMature microRNAs (miRNAs) are single‐stranded RNA molecules of 20–23 nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis and invasion. miRNA targeting is mostly achieved through specific base‐pairing interactions between the 5′ end (‘seed’ region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3′ UTR lead to more effective mRNA destabilization. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. To provide a critical overview of miRNA dysregulation in cancer, we first discuss the methods currently available for studying the role of miRNAs in cancer and then review miRNA genomic organization, biogenesis and mechanism of target recognition, examining how these processes are altered in tumorigenesis. Given the critical role miRNAs play in tumorigenesis processes and their disease‐specific expression, they hold potential as therapeutic targets and novel biomarkers. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Metabolomic pattern of childhood neuroblastoma obtained by 1H‐high‐resolution magic angle spinning (HRMAS) NMR spectroscopy
Authors: Imperiale Alessio , Elbayed Karim , Moussallieh François‐Marie , Neuville Agnès , Piotto Martial , Bellocq Jean‐Pierre , Lutz Patrick , Namer Izzie‐Jacques 
Published: October 2010

AbstractBackgroundThe aim of this preliminary study is to characterize by 1H high‐resolution magic angle spinning NMR spectroscopy (HRMAS) the metabolic content of intact biopsy samples obtained from 12 patients suffering from neuroblastoma (NB).ProcedureThe biochemical NB profile was first compared to normal adrenal medulla. In a second step, the relationship between the tumor metabolic profile and the patients' clinical data was investigated.ResultsA higher level of creatine, glutamine/glutamate, acetate and glycine characterized NB biopsies while healthy adrenal medulla tissue contained adrenaline and a larger amount of ascorbic acid. Adrenaline, which was undetectable in NB spectra, represented the metabolic signature of normal adrenal medulla. NB from patients younger than 12 months contained a higher level of acetate and lysine. Conversely, higher amounts of glutathione, glutamate, myo‐inositol, glycine, serine and ascorbic acid were detected in NB samples belonging to younger children. Glutamine/glutamate, aspartate, creatine, glycine were characteristic of stage I–II NB. Acetate and creatine were characteristic of stage IV NB. Finally, a relatively higher amount of aspartate, succinate, and glutathione was detected in patients alive without active disease after a mean follow‐up of 7 years whereas a higher concentration of acetate and taurine was characteristic of patients with worse prognosis.ConclusionsOur preliminary results suggest the existence of a complex metabolic reality in NB, probably representative of tumor behavior. However, the real impact of these promising results should be assessed by long‐term prospective studies on a larger cohort of patients. Pediatr Blood Cancer. 2010;56:24–34. © 2010 Wiley‐Liss, Inc.
Pyuria is absent during urinary tract infections in neutropenic patients
Authors: Klaassen I.L.M. , de Haas V. , van Wijk J.A.E. , Kaspers G.J.L. , Bijlsma M. , Bökenkamp A. 
Published: October 2010

AbstractTo investigate the diagnostic significance of a normal urine sediment in the work‐up for fever of unknown origin in neutropenia. Urinary tract infection was defined as ≥105 urinary pathogens in the absence of another focus. Pyuria was found in only 1/23 neutropenic episodes compared to 21/31 in controls (P < 0.0001). Pediatr Blood Cancer 2011;56:868–870. © 2010 Wiley‐Liss, Inc.
Proteome and radioimmunoassay analyses of pituitary hormones and proteins in response to feed restriction of dairy cows
Authors: Kuhla Björn , Albrecht Dirk , Bruckmaier Rupert , Viergutz Torsten , Nürnberg Gerd , Metges Cornelia C. 
Published: October 2010

AbstractThe hypothalamic‐pituitary system controls homeostasis during feed energy reduction. In order to examine which pituitary proteins and hormone variants are potentially associated with metabolic adaptation, pituitary glands from ad libitum and energy restrictively fed dairy cows were characterized using RIA and 2‐DE followed by MALDI‐TOF‐MS. We found 64 different spots of regulatory hormones: growth hormone (44), preprolactin (16), luteinizing hormone (LH) (1), thyrotropin (1), proopiomelanocortin (1) and its cleavage product lipotropin (1), but none of these did significantly differ between feeding groups. Quantification of total pituitary LH and prolactin concentrations by RIA confirmed the results obtained by proteome analysis. Also, feed energy restriction provoked increasing non‐esterified fatty acid, decreasing prolactin, but unaltered glucose, LH and growth hormone plasma concentrations. Energy restriction decreased the expression of glial fibrillary acidic protein, triosephosphate isomerase, purine‐rich element‐binding protein A and elongation factor Tu, whereas it increased expression of proline synthetase co‐transcribed homolog, peroxiredoxin III, β‐tubulin and annexin A5 which is involved in the hormone secretion process. Our results indicate that in response to feed energy restriction the pituitary reservoir of all posttranslationally modified hormone forms remains constant. Changing plasma hormone concentrations are likely attributed to a regulated releasing process from the gland into the blood.
Impact of oxidation on protein therapeutics: Conformational dynamics of intact and oxidized acid‐β‐glucocerebrosidase at near‐physiological pH
Authors: Bobst Cedric E. , Thomas John J. , Salinas Paul A. , Savickas Philip , Kaltashov Igor A. 
Published: October 2010

AbstractThe solution dynamics of an enzyme acid‐β‐glucocerebrosidase (GCase) probed at a physiologically relevant (lysosomal) pH by hydrogen/deuterium exchange mass spectrometry (HDX‐MS) reveals very uneven distribution of backbone amide protection across the polypeptide chain. Highly mobile segments are observed even within the catalytic cavity alongside highly protective segments, highlighting the importance of the balance between conformational stability and flexibility for enzymatic activity. Forced oxidation of GCase that resulted in a 40–60% reduction in in vitro biological activity affects the stability of some key structural elements within the catalytic site. These changes in dynamics occur on a longer time scale that is irrelevant for catalysis, effectively ruling out loss of structure in the catalytic site as a major factor contributing to the reduction of the catalytic activity. Oxidation also leads to noticeable destabilization of conformation in remote protein segments on a much larger scale, which is likely to increase the aggregation propensity of GCase and affect its bioavailability. Therefore, it appears that oxidation exerts its negative impact on the biological activity of GCase indirectly, primarily through accelerated aggregation and impaired trafficking.
TEV protease‐facilitated stoichiometric delivery of multiple genes using a single expression vector
Authors: Chen Xi , Pham Elizabeth , Truong Kevin 
Published: October 2010

AbstractDelivery and expression of multiple genes is an important requirement in a range of applications such as the engineering of synthetic signaling pathways and the induction of pluripotent stem cells. However, conventional approaches are often inefficient, nonstoichiometric and may limit the maximum number of genes that can be simultaneously expressed. We here describe a versatile approach for multiple gene delivery using a single expression vector by mimicking the protein expression strategy of RNA viruses. This was accomplished by first expressing the genes together with TEV protease as a single fusion protein, then proteolytically self‐cleaving the fusion protein into functional components. To demonstrate this method in E. coli cells, we analyzed the translation products using SDS‐PAGE and showed that the fusion protein was efficiently cleaved into its components, which can then be purified individually or as a binding complex. To demonstrate this method in mammalian cells, we designed a differential localization scheme and used live cell imaging to observe the distinctive subcellular targeting of the processed products. We also showed that the stoichiometry of the processed products was consistent and corresponded with the frequency of appearance of their genes on the expression vector. In summary, the efficient expression and separation of up to three genes was achieved in both E. coli and mammalian cells using a single TEV protease self‐processing vector.
Preparation of a highly translocation‐competent proOmpA/SecB complex
Authors: Nishiyama Ken‐Ichi , Tokuda Hajime 
Published: October 2010

AbstractMethods for reproducibly preparing highly translocation‐competent proOmpA were developed. Only a competent form of proOmpA was sorted out from incompetent one using SecB, a translocation‐dedicated chaperone, as a probe. Trypsin digestion revealed that the incompetent form of proOmpA was partially folded at its N‐terminus, consistent with the jamming of proOmpA within translocon. Although the incompetent form of proOmpA was not active as to topology inversion of SecG, the isolated proOmpA/SecB complex had recovered the ability of SecG inversion. These results let us prepare a proOmpA/SecB complex both in vivo and in vitro that is highly translocation‐competent. E. coli cells harboring a plasmid, in which ompA and secB were encoded as a synthetic operon, accumulated the proOmpA/SecB complex in the cytosol. The complex, purified by means of a His tag attached to SecB, was found to be translocation‐competent as revealed by the occurrence of SecG inversion, although the signal peptide of proOmpA was sensitive to proteolytic digestion. ProOmpA, in vitro synthesized by means of a continuous exchange cell free system in the presence of SecB‐His, was purified as a complex with SecB, which was active as to SecG inversion as well.
Evidence of epithelial to mesenchymal transition associated with increased tumorigenic potential in an immortalized normal prostate epithelial cell line
Authors: Marian Calin O. , Yang Lin , Zou Ying S. , Gore Crystal , Pong Rey‐Chen , Shay Jerry W. , Kabbani Wareef , Hsieh Jer‐Tsong , Raj Ganesh V. 
Published: October 2010

AbstractBACKGROUNDThe majority of established human prostate cancer cell lines are derived from metastatic lesions and are already tumorigenic in vivo, therefore immortalized normal prostate cell lines may provide a more relevant model to unveil the mechanisms associated with cancer progression and metastasis.METHODSPZ‐HPV‐7, an immortalized human prostate epithelial cell line was used to generate xenograft tumors in mice. A subline designated HPV‐PZ‐7T was subsequently derived from the subrenal capsule xenograft of a nude mouse. These cells were further characterized using karyotyping, immunofluorescence, qRT‐PCR, Western blotting, and three‐dimensional cultures in Matrigel.RESULTSThe PZ‐HPV‐7 cell line possesses a typical epithelial morphology, expresses basal cell markers, and is capable of forming web‐like structures with evidence of budding on Matrigel. PZ‐HPV‐7 is non‐tumorigenic in immunocompromised mice by either subcutaneous injection or subrenal grafting. In contrast, the PZ‐HPV‐7T cells, derived from a xenograft tumor induced by co‐inoculation with matrigel using subrenal grafting, possess a mesenchymal phenotype as well as luminal cell markers and are highly tumorigenic and metastatic in nude mice. Functionally and biochemically, the PZ‐HPV‐7T subline appears to have undergone an epithelial‐to‐mesenchymal transition (EMT) from the parental PZ‐HPV‐7 line.CONCLUSIONWe have developed a novel EMT model using an immortalized normal prostate epithelial cell line and generated a new prostate cancer cell line, PZ‐HPV‐7T, which may represent an excellent system to study mechanisms associated with prostate cancer progression and metastasis. Prostate 71:626–636, 2011. © 2010 Wiley‐Liss, Inc.
Gastrin‐releasing peptide: Predictor of castration‐resistant prostate cancer?
Authors: Heinrich Elmar , Probst Kai , Michel Maurice Stephan , Trojan Lutz 
Published: October 2010

AbstractBACKGROUNDNeuroendocrine (NE) cells of the prostate are known to be androgen‐independent and NE peptides like gastrin‐releasing peptide (GRP) or neuron‐specific enolase (NSE) can stimulate growth in a paracrine manner, and this is thought to be one of the escape mechanisms in castration‐resistant prostate cancer (CRPCa). In a longitudinal study, we investigated the development of the NE serum factors GRP, NSE, and chromogranin A and their correlation with prostate‐specific androgen (PSA) during hormonal treatment.MATERIALS AND METHODSThirty two patients, with histology‐proven, localized or metastatic prostatic carcinoma (PCa), who were undergoing therapy with LHRH analogue or a combination of LHRH analog and peripheral androgen blockade, took part in the study. In addition, eight healthy volunteers were each tested twice for serum GRP to elicit a “physiological” standard value. Blood samples were taken periodically from each patient within an 18‐month time frame.RESULTSWe defined the standard value for GRP in the healthy participants as 0.852 ng/ml (mean + 2 SD) and observed that the GRP values for patients with PCa were significantly higher (P = 0.034). There was a positive correlation between PSA and GRP in patients with biochemical failure. CgA correlated with PSA development in the CRPCa patients. NSE values rose steadily over the study period, but with no correlation to PSA.CONCLUSIONOur data confirm that NE factors are elevated during hormonal treatment of prostate cancer. GRP is higher in PCa patients undergoing androgen deprivation therapy and is possibly involved in the initiation of hormonal escape in PCa. Prostate 71:642–648, 2011. © 2010 Wiley‐Liss, Inc.