bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barrier and Mechanical Properties of Starch‐Clay Nanocomposite Films
Authors: Tang Xiaozhi , Alavi Sajid , Herald Thomas J. 
Published: May 2008

ABSTRACTThe poor barrier and mechanical properties of biopolymer‐based food packaging can potentially be enhanced by the use of layered silicates (nanoclay) to produce nanocomposites. In this study, starch‐clay nanocomposites were synthesized by a melt extrusion method. Natural (MMT) and organically modified (I30E) montmorillonite clays were chosen for the nanocomposite preparation. The structures of the hybrids were characterized by X‐ray diffraction (XRD) and transmission electron microscopy (TEM). Films were made through casting using granulate produced by a twin‐screw extruder. Starch/MMT composite films showed higher tensile strength and better water vapor barrier properties than films from starch/I30E composites, as well as pristine starch, due to formation of intercalated nanostructure. To find the best combinations of raw materials, the effects of clay content (0–21 wt% MMT), starch sources (corn, wheat, and potato), and amylose content (≈0, 28, 55, 70, 100%) on barrier and mechanical properties of the nanocomposite films were investigated. With increase in clay content, significantly higher (15–92%) tensile strength (TS), and lower (22–67%) water vapor permeability (WVP) were obtained. The barrier and mechanical properties of nanocomposite films did not vary significantly with different starch sources. Nanocomposite films from regular corn starch had better barrier and mechanical properties than either high amylopectin or high‐amylose‐based nanocomposite films. WVP, TS, and elongation at break (%E) of the films did not change significantly as amylose content increased beyond 50%.
Crystal structures of Melanocarpus albomyces cellobiohydrolase Cel7B in complex with cello‐oligomers show high flexibility in the substrate binding
Authors: Parkkinen Tarja , Koivula Anu , Vehmaanperä Jari , Rouvinen Juha 
Published: May 2008

AbstractCellobiohydrolase from Melanocarpus albomyces (Cel7B) is a thermostable, single‐module, cellulose‐degrading enzyme. It has relatively low catalytic activity under normal temperatures, which allows structural studies of the binding of unmodified substrates to the native enzyme. In this study, we have determined the crystal structure of native Ma Cel7B free and in complex with three different cello‐oligomers: cellobiose (Glc2), cellotriose (Glc3), and cellotetraose (Glc4), at high resolution (1.6–2.1 Å). In each case, four molecules were found in the asymmetric unit, which provided 12 different complex structures. The overall fold of the enzyme is characteristic of a glycoside hydrolase family 7 cellobiohydrolase, where the loops extending from the core β‐sandwich structure form a long tunnel composed of multiple subsites for the binding of the glycosyl units of a cellulose chain. The catalytic residues at the reducing end of the tunnel are conserved, and the mechanism is expected to be retaining similarly to the other family 7 members. The oligosaccharides in different complex structures occupied different subsite sets, which partly overlapped and ranged from −5 to +2. In four cellotriose and one cellotetraose complex structures, the cello‐oligosaccharide also spanned over the cleavage site (−1/+1). There were surprisingly large variations in the amino acid side chain conformations and in the positions of glycosyl units in the different cello‐oligomer complexes, particularly at subsites near the catalytic site. However, in each complex structure, all glycosyl residues were in the chair (4C1) conformation. Implications in relation to the complex structures with respect to the reaction mechanism are discussed.
Sitagliptin, an dipeptidyl peptidase‐4 inhibitor, does not alter the pharmacokinetics of the sulphonylurea, glyburide, in healthy subjects
Authors: Mistry Goutam C. , Bergman Arthur J. , Zheng Wei , Hreniuk David , Zinny Miguel A. , Gottesdiener Keith M. , Wagner John A. , Herman Gary A. , Ruddy Marcella 
Published: May 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • No data are available on the potential drug interaction of sitagliptin and glyburide.• Sitagliptin belongs to a new class of drugs called DPP‐4 inhibitors recently approved for the treatment of Type 2 diabetes. WHAT THIS STUDY ADDS • Glyburide is a commonly used sulphonylurea medication to treat Type 2 diabetes.• Combination therapy is often required to achieve adequate glucose control in Type 2 diabetes.• Sitagliptin does not appear to interfere with glyburide pharmacokinetics and therefore may be potentially co‐administered with glyburide for the treatment of Type 2 diabetes.AIMSSitagliptin, a dipeptidyl peptidase‐4 inhibitor, is an incretin enhancer that is approved for the treatment of Type 2 diabetes. Sitagliptin is mainly renally eliminated and not an inhibitor of CYP450 enzymes in vitro. Glyburide, a sulphonylurea, is an insulin sensitizer and mainly metabolized by CYP2C9. Since both agents may potentially be co‐administered, the purpose of this study was to examine the effects of sitagliptin on glyburide pharmacokinetics.METHODSIn this open‐label, randomized, two‐period crossover study, eight healthy normoglycaemic subjects, 22–44 years old, received single 1.25‐mg doses of glyburide alone in one period and co‐administered with sitagliptin on day 5 following a multiple‐dose regimen for sitagliptin (200‐mg q.d. ×6 days) in the other period.RESULTSThe geometric mean ratios and 90% confidence intervals [(glyburide + sitagliptin)/glyburide] for AUC0–∞ and Cmax were 1.09 (0.96, 1.24) and 1.01 (0.84, 1.23), respectively.CONCLUSIONSitagliptin does not alter the pharmacokinetics of glyburide in healthy subjects.
Analysis of a large multi‐generational family provides insight into the genetics of chronic lymphocytic leukemia
Authors: Fuller Stephen J. , Papaemmanuil Elli , McKinnon Leah , Webb Emily , Sellick Gabrielle S. , Dao‐Ung Lan‐Phuong , Skarratt Kristen K. , Crowther Dalemari , Houlston Richard S. , Wiley James S. 
Published: May 2008

SummaryWe report the genetic analysis of a large multi‐generational family composed of 144 individuals in which 11 members have been diagnosed with chronic lymphocytic leukaemia (CLL). The observation of a significant over‐representation of monoclonal B‐cell lymphocytosis (MBL) in unaffected family members strongly supports MBL being a surrogate marker of carrier status. A genome‐wide linkage scan of the family using high‐density 10K single nucleotide polymorphisms provided no significant evidence for a single gene model of disease susceptibility, inviting speculation that susceptibility to CLL has a more complex basis. The absence of a correlation in IGHV usage between affected family members does however argue strongly against exposure to a single super‐antigen in disease development.
The labile iron pool in human erythroid cells
Authors: Prus Eugenia , Fibach Eitan 
Published: May 2008

SummaryAlthough most cellular iron is firmly bound (e.g. in haemoglobin), some, the labile iron pool (LIP), is bound to low‐affinity ligands. The LIP is regarded as the crossroads of cellular iron traffic. Using multi‐parameter flow‐cytometry of cells treated with the metal‐sensitive sensor calcein and the cell‐permeable chelator deferiprone, we studied LIP in various human erythroid cell populations in peripheral blood, bone marrow and culture. Erythroid maturation was found to be associated with a decrease in the LIP. In the peripheral blood, nucleated erythrocytes (normoblasts) had 5·8‐fold and 8·8‐fold greater LIP than reticulocytes and erythrocytes respectively. Early reticulocytes had 2·5‐fold more LIP than late reticulocytes. In the bone‐marrow and in culture, LIP decreased by c. 30‐fold as early erythroid precursors matured to late precursors. Adding holo‐transferrin to iron‐depleted cultures elevated LIP by 3·9‐fold. We also show that in β‐thalassaemia, a disease associated with iron‐overload, erythrocytes and reticulocytes in the blood and erythroid precursors in culture have a significantly greater LIP than their normal counterparts. In conclusion, the LIP in erythroid cells is altered under physiological (maturation) and pathological (thalassaemia) conditions. The methodology presented might be useful for evaluating the LIP in various diseases and for studying the efficacy of iron‐chelators.
Effects on erythropoiesis of alemtuzumab‐containing reduced intensity and standard conditioning regimens
Authors: Mijovic Aleksandar , Abdallah Atiyeh , Pearce Laurence , Tobal Khalid , Mufti Ghulam J. 
Published: May 2008

SummaryHaemopoietic cell transplantation (HCT) with reduced‐intensity conditioning (RIC) has been associated with delayed disappearance of host anti‐A and anti‐B isohaemaglutinins and hindrance of donor erythropoiesis in major ABO mismatched transplants. Erythroid recovery, disappearance of recipient type and appearance of donor‐type isohaemaglutinins was compared in 84 patients undergoing RIC and 50 patients with standard‐conditioning (SCo) HCT. All patients received alemtuzumab as part of their conditioning. The incidence of immune‐mediated anaemia and red cell transfusion usage were also compared. Immune factors affecting post‐transplant erythroid kinetics showed little variance between different conditioning regimens. Disappearance of recipient isohaemaglutinins and emergence of donor red cells proceeded at similar rates in RIC and SCo transplants; the effects of ABO mismatch were marginal. Pure red cell aplasia, alloimmune haemolysis and autoimmune haemolytic anaemia were not more common in RIC transplants. We believe that alemtuzumab played a critical role in dampening immune reactions of both the host and the donor. Patients in both conditioning groups had similar post‐transplant erythroid burst‐forming unit (BFU‐E) counts; BFU‐E chimaerism analysis showed that 90–100% progenitors were of donor origin. However, transfusion requirements were significantly higher in the SCo group, due at least partly to earlier onset of bone marrow hypoplasia.
Expression of Concern: HSP70 inhibition reverses cell adhesion mediated and acquired drug resistance in multiple myeloma
Authors: Nimmanapalli Ramadevi , Gerbino Elvira , Dalton William S. , Gandhi Varsha , Alsina Melissa 
Published: May 2008

SummaryHeat shock proteins (HSPs) are a super family of highly conserved molecular chaperone proteins, which are induced in response to stress. HSP70 has been demonstrated to inhibit apoptosis induced by a number of chemotherapeutic agents. Previous investigations have suggested the development of drug resistance in multiple myeloma (MM) cells after adhesion to stroma. This study used MM cell lines and primary plasma cells to determine if HSP70 had a role in development of chemo resistance. Adhesion of MM cells to either bone marrow stromal cells or fibronectin (FN) enhanced HSP70 expression. Inhibition of the HSP70 expression decreased 8226 cell adhesion to stroma or FN and induced more apoptosis in FN‐adhered 8226 cells than in suspension cultures at 24 h. Further, HSP70 inhibitors enhanced melphalan‐induced apoptosis and reversed melphalan‐induced cell adhesion‐mediated drug resistance (CAM‐DR) phenotype. In addition, compared to parental cells, KNK‐437, a heat shock factor inhibitor caused more apoptosis in melphalan‐resistant 8226/LR5 cells and sensitized them to melphalan. Primary CD138 positive cells showed high expression of HSPA4 mRNA, and KNK‐437 caused apoptosis in these cells. In conclusion, our data suggest inhibition of HSP70, reduced adhesion and caused apoptosis of both acquired and de novo drug resistant MM cells.
South Asian chronic lymphocytic leukaemia patients have more rapid disease progression in comparison to White patients
Authors: Gunawardana Chaminda , Austen Belinda , Powell Judith E. , Fegan Christopher , Wandroo Farooq , Jacobs Abe , Pratt Guy , Moss Paul 
Published: May 2008

SummaryEthnicity has a major impact on the prevalence of chronic lymphocytic leukaemia (CLL) and may also influence disease phenotype. We compared the clinical features of Southern Asian and White CLL patients managed within one UK region. Asians required treatment almost twice as often as Whites (HR, 1·94) and had a shorter time to first treatment (P = 0·0063). This difference remained significant after adjusting for stage, lymphocyte doubling time and IGHV status (P = 0·026). CLL was diagnosed at younger ages in Asians and racial‐specific variations in IGHV usage were demonstrated. Our findings indicate that Southern Asian race has a negative impact on CLL phenotype.
Retracted: A modified version of galectin‐9 induces cell cycle arrest and apoptosis of Burkitt and Hodgkin lymphoma cells
Authors: Makishi Shoko , Okudaira Taeko , Ishikawa Chie , Sawada Shigeki , Watanabe Toshiki , Hirashima Mitsuomi , Sunakawa Hajime , Mori Naoki 
Published: May 2008

SummaryThe identification of galectin‐9 as a ligand for T‐cell immunoglobulin‐ and mucin‐domain‐containing molecule‐3 (Tim‐3), expressed on T‐helper type‐1 (Th1) cells, has established the Tim‐3‐galectin‐9 pathway as a regulator of Th1 immunity. Whereas there is compelling evidence for the effects of galectin‐9 on T‐cell fate, limited information is available on the impact of galectin‐9 on B lymphocytes. We found that protease‐resistant galectin‐9, hG9NC(null), but not galectin‐1 or ‐8, prevented cell growth of malignant B cells, such as Burkitt lymphoma (BL) and Hodgkin lymphoma (HL). β‐galactoside binding was essential for galectin‐9‐induced cell growth suppression. hG9NC(null) induced cell cycle arrest by reducing the expression of cyclin D1, D2, B1, Cdk4, Cdc25C and c‐Myc, and apoptosis by reducing the expression of XIAP, c‐IAP2 and survivin. Most of the genes that encode these proteins are regulated by nuclear factor‐κB (NF‐κB), and constitutive activation of NF‐κΒ is a common characteristic of both types of malignancies. hG9NC(null) inhibited IκBα phosphorylation, resulting in suppression of NF‐κB. AP‐1 has also been implicated in the control of cell survival. hG9NC(null) inhibited the expression of JunD, resulting in the suppression of AP‐1. Our results suggest that hG9NC(null) is a potentially suitable agent for the management of BL and HL.
Asp–Tyr–Leu–Lys tetrapeptide inhibits airway inflammation in toluene‐2,4‐diisocyanate‐induced asthma mice
Authors: Ahn M‐H. , Park B‐J. , Kwon J‐H. , An S‐H. , Park J‐W. , Jang A. S. , Rhim T. , Park C‐S. 
Published: May 2008

SummaryBackground
Airway inflammation and remodelling contribute to chronic airway obstruction of asthma. Currently, no medication effectively controls airway remodelling and related vascular changes. Therefore, new strategies need to be developed. The kringle 5 domain has anti‐angiogenic activity resulting from the tetrapeptide Lys–Leu–Tyr–Asp (KLYD).Objective
To investigate the therapeutic effect of KLYD and its inverse form Asp‐Tyr‐Leu‐Lys (DYLK) on the inflammation and remodelling of toluene‐2,4‐diisocyanate (TDI)‐sensitization/challenged mice.Methods
Cell numbers were measured in the presence of various concentrations of KLYD and DYLK using in vitro endothelial cell proliferation assay. The changes of cell number and the level of vascular endothelial growth factor (VEGF) in bronchoalveolar lavage (BAL) fluid and response to methacholine (MCh) were measured using the in vivo TDI‐sensitized/challenged mice model. Muc5ac, smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA) protein expression was analysed on trachea and intrapulmonary bronchi using immunohistochemical stain.Results
Compared with KLYD, DYLK had a greater inhibitory effect on endothelial cell proliferation (P<0.05). Pre‐treatment of DYLK showed dose‐dependent reduction in the response to MCh (P<0.05) and numbers of inflammatory cells in BAL fluids of TDI‐sensitized/challenged mice. TDI induced increases in Muc5ac, SMA and PCNA protein expression and VEGF levels, which were also abolished by DYLK treatment.Conclusions
Local administration of DYLK effectively inhibits the airway inflammation and airway remodelling of TDI‐sensitized/challenged mice via down‐regulation of VEGF. These findings suggest that anti‐angiogenic peptide therapies, such as local administration of DYLK, are an effective strategy for the treatment of remodelling in asthma.
Specific allergy to Penaeus monodon (seawater shrimp) or Macrobrachium rosenbergii (freshwater shrimp) in shrimp‐allergic children
Authors: Jirapongsananuruk O. , Sripramong C. , Pacharn P. , Udompunturak S. , Chinratanapisit S. , Piboonpocanun S. , Visitsunthorn N. , Vichyanond P. 
Published: May 2008

SummaryBackground
Allergy to specific shrimp species has not been studied systematically by oral challenges. A comparison of allergy to different shrimp species, especially seawater or freshwater varieties treatment, would be useful in testing shrimp‐allergic subjects.Objective
The aim of the study was to identify cases of specific allergy to seawater shrimp, Penaeus monodon (Pm), or freshwater shrimp, Macrobrachium rosenbergii (Mr), among shrimp‐allergic children. Comparisons of skin tests using commercial and crude shrimp extracts plus the prick‐to‐prick (PTP) method were investigated.Methods
Sixty‐eight children with a history of shrimp allergy and skin tests positive to shrimp were orally challenged to both shrimp species. Reactivity to skin prick tests using extracts of Pm (PmSPT), Mr (MrSPT), commercial shrimp (ComSPT), and PTP tests (PmPTP, MrPTP) was compared.Results
Food challenges identified specific allergy to Pm and Mr in 17.65% and 23.53% of the subjects, respectively. Positive and negative challenges to both shrimp species were found in 47.06% and 11.76% of the subjects, respectively. Correlations between the mean weal diameter (MWD) from ComSPT–PmSPT, ComSPT–PmPTP, ComSPT–MrPTP, PmSPT–PmPTP and MrSPT–MrPTP, but not ComSPT–MrSPT, were observed. The MWD from PmSPT and PmPTP were significantly larger in patients with positive than negative challenges to P. monodon (P<0.05). There was a trend that MWD from MrSPT were larger in patients with positive than negative challenges to M. rosenbergii (P=0.058). In the Pm allergy group, PmSPT with an MWD of 30 mm provided 80% predictive probability for positive challenges. PmPTP and ComSPT with an MWD of 22.5 and 20 mm provided 95% predictive probability, respectively. In the Mr allergy group, MrSPT with an MWD of 30 mm provided 95% predictive probability.Conclusion
Specific allergy to Pm or Mr was confirmed by food challenges. SPT using crude extracts and the PTP test are useful tools for screening shrimp sensitization before a food challenge. The predictive probability of SPT is helpful where a food challenge is not feasible.
Human innate immune responses to hexamethylene diisocyanate (HDI) and HDI–albumin conjugates
Authors: Wisnewski A. V. , Liu Q. , Liu J. , Redlich C. A. 
Published: May 2008

SummaryBackground
Isocyanates, a leading cause of occupational asthma, are known to induce adaptive immune responses; however, innate immune responses, which generally precede and regulate adaptive immunity, remain largely uncharacterized.Objective
The aim of the study was to identify and characterize the cellular, molecular and systemic innate immune responses induced by hexamethylene diisocyanate (HDI).Methods
Human peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with HDI–albumin conjugates or control antigen, and changes in phenotype, gene and protein expression were characterized by flow cytometry, microarray, Western blot and ELISA. Cell uptake of isocyanate was visualized microscopically using HDI–albumin conjugates prepared with fluorescently labelled albumin. In vivo, human HDI exposure was performed via a specific inhalation challenge, and subsequent changes in PBMCs and serum proteins were measured by flow cytometry and ELISA. Genotypes were determined by PCR.Results
Human monocytes take up HDI–albumin conjugates and undergo marked changes in morphology and gene/protein expression in vitro. The most significant (P‐values 0.007–0.05) changes in mircoarray gene expression were noted in lysosomal genes, especially peptidases and proton pumps involved in antigen processing. Chemokines that regulate monocyte/macrophage trafficking (MIF, MCP‐1) and pattern‐recognition receptors that bind chitin (chitinases) and oxidized low‐density lipoprotein (CD68) were also increased following isocyanate–albumin exposure. In vivo, HDI‐exposed subjects exhibited a drastic increase in the percentage of PBMCs with the same HDI–albumin responsive phenotype characterized in vitro (HLA‐DR+/CD11c+ with altered light scatter properties). An exposure‐dependent decrease (46±11%; P<0.015) in serum concentrations of chitinase 3‐like‐1 was also observed in individuals who lack the major (type 1) human chitinase (due to genetic polymorphism), but not in individuals possessing at least one functional chitinase‐1 allele.Conclusions
Previously unrecognized innate immune responses to HDI and HDI–albumin conjugates could influence the clinical spectrum of exposure reactions.
Cow's milk protein sensitivity assessed by the mucosal patch technique is related to irritable bowel syndrome in patients with primary Sjögren's syndrome
Authors: Lidén M. , Kristjánsson G. , Valtysdottir S. , Venge P. , Hällgren R. 
Published: May 2008

SummaryIntroduction
Patients with primary Sjögren's syndrome (pSS) are reported to have a variety of gastrointestinal symptoms partly attributed to an overrepresentation of celiac disease. We have observed that irritable bowel syndrome (IBS)‐like symptoms are frequent complaints in this patient group. Allergic manifestations to various drugs are also common in pSS. A role of food allergy in IBS has been proposed.Objective
This study is aimed at evaluating the mucosal response to rectal challenge with cow's milk protein (CM) in patients with pSS and relates possible CM reactivity to their intestinal symptoms.Methods
A rectal challenge with CM was performed in 21 patients with pSS and 18 healthy controls. Fifteen hours after challenge the mucosal production of nitric oxide (NO) and the release of myeloperoxidase (MPO) as signs of mucosal inflammatory reaction were measured using the mucosal patch technique.Results
Eight out of 21 patients with pSS had a definite increase of mucosal NO synthesis and the luminal release of MPO after rectal CM challenge. This sign of milk sensitivity was not linked to IgG/IgA antibodies to milk proteins. The symptoms for IBS according to Rome III criteria were fulfilled in 13 patients. All patients who were CM sensitive suffered from IBS. In a small open study, patients reactive to CM reported an improvement of intestinal symptoms on a CM‐free diet.Conclusion
A rectal mucosal inflammatory response after CM challenge is seen in 38% of patients with pSS as a sign of CM sensitivity. IBS‐like symptoms were common in pSS, linked to CM sensitivity.