bluuebunny/crossref_metadata_2025_split huggingface dataset:
BIRB 796 enhances cytotoxicity triggered by bortezomib, heat shock protein (Hsp) 90 inhibitor, and dexamethasone via inhibition of p38 mitogen‐activated protein kinase/Hsp27 pathway in multiple myeloma cell lines and inhibits paracrine tumour growth
Authors: Yasui Hiroshi , Hideshima Teru , Ikeda Hiroshi , Jin Janice , Ocio Enrique M. , Kiziltepe Tanyel , Okawa Yutaka , Vallet Sonia , Podar Klaus , Ishitsuka Kenji , Richardson Paul G. , Pargellis Chris , Moss Neil , Raje Noopur , Anderson Kenneth C. 
Published: December 2006

SummaryWe have previously shown that heat shock protein (Hsp) 27 or its upstream activator p38 mitogen‐activated protein kinase (MAPK) confers resistance to bortezomib and dexamethasone (Dex) in multiple myeloma (MM) cells. This study examined anti‐MM activity of a novel p38 MAPK inhibitor, BIRB 796, alone and in combination with conventional and novel therapeutic agents. BIRB 796 blocked baseline and bortezomib‐triggered upregulation of p38 MAPK and Hsp27 phosphorylation, thereby enhancing cytotoxicity and caspase activation. The Hsp90 inhibitor 17‐allylamino‐17‐demethoxy‐geldanamycin (17‐AAG) upregulated protein expression and phosphorylation of Hsp27; conversely, BIRB 796 inhibited this phosphorylation and enhanced 17‐AAG‐induced cytotoxicity. Importantly, BIRB 796 inhibited Hsp27 phosphorylation induced by 17‐AAG plus bortezomib, thereby enhancing cytotoxicity. In bone marrow stromal cells (BMSC), BIRB 796 inhibited phosphorylation of p38 MAPK and secretion of interleukin‐6 (IL‐6) and vascular endothelial growth factor triggered by either tumour necrosis factor‐α or tumour growth factor‐β1. BIRB 796 also inhibited IL‐6 secretion induced in BMSCs by adherence to MM cells, thereby inhibiting tumour cell proliferation. These studies therefore suggest that BIRB 796 overcomes drug‐resistance in the BM microenvironment, providing the framework for clinical trials of a p38 MAPK inhibitor, alone and in combination with bortezomib, Hsp90 inhibitor, or Dex, to improve patient outcome in MM.
Activated platelet‐derived microparticles in thalassaemia
Authors: Pattanapanyasat Kovit , Gonwong Siriphan , Chaichompoo Porntip , Noulsri Egarit , Lerdwana Surada , Sukapirom Kasama , Siritanaratkul Noppadol , Fucharoen Suthat 
Published: December 2006

SummaryThromboembolic complications have been documented in thalassaemia patients. The aggregability of abnormal red blood cells and the high level of membrane‐derived microparticles (MPs) stemming from blood cells are thought to be responsible for the associated thrombotic risk. We investigated the number of MPs, their cellular origin and their procoagulant properties in β‐thalassaemia. Fresh whole blood was simultaneously stained for annexin V, cellular antigens and the known density beads. The procoagulant properties of these phosphatidylserine (PS)‐bearing MPs were also measured by assessing the platelet factor‐3‐like activity in the blood. Flow cytometric results showed that splenectomised β‐thalassaemia/HbE patients had significantly higher levels of PS‐bearing MPs than non‐splenectomised β‐thalassaemia/HbE patients and normal individuals (P < 0·0001). There was a good correlation between PS‐bearing MPs and PS‐bearing platelets, reflecting the existence of chronic platelet activation in β‐thalassaemia/HbE patients (rs = 0·511, P < 0·001). The cellular origin of PS‐bearing MPs showed mostly activated‐platelet origin with adhesion (CD41a/CD62P/CD36). Moreover, the platelet procoagulant activity was higher in splenectomised β‐thalassaemia/HbE patients when compared with non‐splenectomised (P < 0·05) and normal individuals (P < 0·01), and the amount correlated with PS‐bearing MPs (rs = 0·560, P < 0·001). These findings suggest that MPs originate from activated platelets with a potential to aggravate thrombotic events when the numbers are excessive, as is commonly seen in splenectomised β‐thalassaemia/HbE patients.
The C‐terminus of α2‐antiplasmin interacts with endothelial cells
Authors: Thomas L. , Moore N. R. , Miller S. , Booth N. A. 
Published: December 2006

SummaryThe serpin, α2‐antiplasmin (α2AP), has an extended C‐terminus relative to other inhibitors. This 51‐residue region contains an RGD sequence; such sequences constitute a key recognition sequence for cell adhesion, mediated through integrins. In the present study, this sequence was expressed in Escherichia coli and its binding to endothelial cells and whether binding depends on the RGD sequence was investigated. Binding to the surface of human umbilical vein endothelial cells (HUVEC‐C) was observed by flow cytometry and immunohistochemistry. Binding studies on immobilised cells showed specific and RGD‐dependent binding of the peptides to HUVEC‐C. The binding of the wild‐type peptide to the HUVEC‐C was significantly higher than that of a mutant peptide, in which RGD was replaced by SAA (P < 0·05, n = 4). Similarly, ethylenediaminetetraacetic acid decreased the binding of the wild‐type peptide (P < 0·05, n = 4). The binding was competed out by full‐length α2AP, fibronectin and anti‐α5β1. This is the first evidence of binding of the C‐terminus of α2AP to endothelial cells via its RGD sequence, with most but not all of the binding being integrin‐mediated. We speculate that this interaction with α2AP may potentially play a role in the control of cellular fibrinolysis by regulating local plasmin activity on cell surfaces.
Juvenile hormone and colony conditions differentially influence cytochrome P450 gene expression in the termite Reticulitermes flavipes*
Authors: Zhou X. , Song C. , Grzymala T. L. , Oi F. M. , Scharf M. E. 
Published: December 2006

AbstractIn lower termites, the worker caste is a totipotent immature stage that is capable of differentiating into other adult caste phenotypes. We investigated the diversity of family 4 cytochrome P450 (CYP4) genes in Reticulitermes flavipes workers, with the specific goal of identifying P450s potentially involved in regulating caste differentiation. Seven novel CYP4 genes were identified. Quantitative real‐time PCR revealed the tissue distribution of expression for the seven CYP4s, as well as temporal expression changes in workers in association with a release from colony influences and during juvenile hormone (JH)‐induced soldier caste differentiation. Several fat‐body‐related CYP4 genes were differentially expressed after JH treatment. Still other genes changed expression in association with removal from colony influences, suggesting that primer pheromones and/or other colony influences impact their expression. These findings add to a growing database of candidate termite caste‐regulatory genes, and provide explicit evidence that colony factors influence termite gene expression.
Specific interactions among odorant‐binding proteins of the African malaria vector Anopheles gambiae
Authors: Andronopoulou E. , Labropoulou V. , Douris V. , Woods D. F. , Biessmann H. , Iatrou K. 
Published: December 2006

AbstractIn this report we present results from a comprehensive study undertaken toward the identification of proteins interacting with odourant‐binding proteins (OBPs) of the African malaria vector Anopheles gambiae with a focus on the interactions among different OBPs. From an initial screen for proteins that interact with a member of the Plus‐C group of OBPs, OBP48, which is primarily expressed in female antennae and downregulated after a blood meal, a number of interacting proteins were identified, which included five classic OBPs and OBP48 itself. The interacting OBPs as well as a number of other classic and Plus‐C group OBPs that were not identified in the initial screen, were expressed in lepidopteran cells and subsequently examined for in vitro interactions in the absence of exogenously added ligands. Co‐immunoprecipitation and chemical cross‐linking studies suggest that OBP48 is capable of homodimerizing, heterodimerizing and forming higher order complexes with those examined examples of classical OBPs identified in the initial screen but not with other classical or Plus‐C group OBPs that failed to appear in the screen. The latter OBPs are, however, also capable of forming homodimers in vitro and, at least in the case of two examined classic OBPs, heterodimers as well. These results suggest a previously unsuspected potential of nonrandom combinatorial complexity that may be crucial for odour discrimination by the mosquito.
cDNA cloning, heat shock regulation and developmental expression of the hsp83 gene in the Mediterranean fruit fly Ceratitis capitata
Authors: Theodoraki M. A. , Mintzas A. C. 
Published: December 2006

AbstractThis report presents the cDNA cloning, heat shock regulation and developmental expression of the hsp90 gene homologue of the Mediterranean fruit fly Ceratitis capitata (medfly). The isolated cDNA contained the coding region, the 3′UTR and most of the 5′UTR of the medfly hsp90 homologue, which was named Cchsp83. The deduced CcHSP83 polypeptide contained all the highly conserved amino acid segments that characterize the cytosolic members of the HSP90 family. Genomic analysis showed that the Cchsp83 gene is unique and was mapped at the 94C division of the sixth polytene chromosome. The size of the Cchsp83 mRNA was found to be approximately 2.7 kb. The predicted molecular mass of the CcHSP83 protein was 81.4 kDa, while the apparent molecular weight estimated by SDS‐PAGE was approximately 90 kDa. Phylogenetic analysis based on 14 insect HSP90 amino acid sequences was consistent with the known phylogeny at low taxonomic level. The Cchsp83 gene is constitutively expressed in all stages of medfly development and is induced from a low level to several‐fold by heat, depending on the developmental stage. Heat shock induction begins at 30 °C, reaching a maximum between 35 and 41 °C. Cchsp83 RNA expression is highly regulated during embryonic development; however, the temporal fluctuations in RNA levels during embryogenesis were not followed by similar fluctuations in the levels of the protein.
Gliding motility and polarized slime secretion
Authors: Yu Rosa , Kaiser Dale 
Published: December 2006

SummaryMyxococcus leaves a trail of slime on agar as it moves. A filament of slime can be seen attached to the end of a cell, but it is seen only at one end at any particular moment. To identify genes essential for A motility, transposon insertion mutations with defective A motility were studied. Fifteen of the 33 mutants had totally lost A motility. All these mutant cells had filaments of slime emerging from both ends, indicating that bipolar secretion prevents A motility. The remaining 18 A motility mutants, also produced by gene knockout, secreted slime only from one pole, but they swarmed at a lower rate than A+ and are called ‘partial’ gliding mutants, or pgl. For each pgl mutant, the reduction in swarm expansion rate was directly proportional to the reduction in the coefficient of elasticotaxis. The pgl mutants have a normal reversal frequency and normal gliding speed when they move. But their probability of movement per unit time is lower than pgl+ cells. Many of the pgl mutants are produced by transposon insertions in glycosyltransferase genes. It is proposed that these glycosyltransferases carry out the synthesis of a repeat unit polysaccharide that constitutes the slime.
Dual role of the MgtC virulence factor in host and non‐host environments
Authors: Rang Cécile , Alix Eric , Felix Christine , Heitz Annie , Tasse Lena , Blanc‐Potard Anne‐Béatrice 
Published: December 2006

SummaryMgtC is required for intramacrophage replication of intracellular pathogens and growth in low Mg2+ medium. A link between these two phenotypes has been proposed due to putative Mg2+ deprivation inside phagosome. MgtC is part of a family of proteins that share a conserved N‐terminal transmembrane domain and a variable C‐terminal domain. A combination of predictive and experimental approaches indicates that the Salmonella MgtC C‐terminal domain is cytoplasmic, adopts a fold also found in metal transporters and RNA interacting domain, and does not bind Mg2+. MgtC homologues from diverse γ‐proteobacteria, including the extracellular pathogens Yersinia pestis, Photorhabdus luminescens and Pseudomonas aeruginosa, have been expressed in a SalmonellaΔmgtC strain. The Y. pestis MgtC fully replaced the Salmonella MgtC whereas P. luminescens or P. aeruginosa MgtC complemented only in low Mg2+ medium, thus dissociating for the first time the two MgtC‐related phenotypes. In addition, we identified single amino acids changes that prevent or promote MgtC role in macrophages without affecting MgtC role in low Mg2+ culture. A SalmonellaΔmgtC strain showed elongated and autoaggregated bacteria in low Mg2+ medium but not in macrophages. Taken together our results suggest that MgtC has a dual role when bacteria localize in macrophages or low Mg2+ environment.
Complement and C4 Null Alleles in Severe Chronic Adult Periodontitis
Authors: Seppänen M. , Lokki M.‐L. , Notkola I.‐L. , Mattila K. , Valtonen V. , Nieminen A. , Vesanen M. , Asikainen S. , Meri S. 
Published: December 2006

AbstractSevere forms of chronic periodontitis affect up to 10% of adults. Tumour necrosis factor and lymphotoxin‐α genes in the major histocompatibility complex are associated with severe periodontitis. Complement factor C4 is a nearby, polymorphic, functionally relevant gene region. Although associated with chronic mucosal infections, C4 deficiencies have not been assessed in adult periodontitis patients. We tested whether complement levels are systemically altered and C4 deficiencies associated with severe chronic periodontitis. In a case–control study, we analysed levels of plasma C3, and C4, serum classical pathway haemolytic activity, C4 allotypes and C4 gene numbers in 37 patients with severe chronic periodontitis and in 150 voluntary controls. Plasma levels of C3 were higher, and classical pathway haemolytic activity was lower in patients than in controls. Partial C4 gene deficiencies were more frequent in patients than in controls (odds ratio 2.4, 95% confidence interval 1.1–5.5, P = 0.032). Changes in complement levels may reflect chronic, recurring inflammation. C4 gene deficiencies are associated with predisposition to chronic periodontitis.
Kappa immunoglobulin light chain polymorphisms and survival after allogeneic transplantation for B‐cell malignancies: a potential graft‐vs‐leukaemia target
Authors: Etto T. L. , Stewart L. A. , Muirhead J. , Bailey M. , Schwarer A. P. 
Published: December 2006

AbstractIn the human leucocyte antigen (HLA)‐matched haematopoietic stem cell transplantation (HSCT) setting, minor histocompatibility antigen (mHA) disparities between recipient and donor can lead to graft‐vs‐host disease (GVHD) or graft rejection. Graft‐vs‐leukaemia (GVL) effect is a beneficial T‐cell‐mediated immune response that can also occur following HLA‐matched HSCT. mHAs with tissue expression restricted to cells of the haematopoietic system are particularly relevant as immunotherapeutic targets for destroying malignant cells without inducing GVHD. Therefore, it is important to identify further haematopoietic‐restricted polymorphic mHAs, which may have the potential to be used clinically for adoptive immunotherapy. Polymorphic mismatching of minor antigens, such as the B‐cell‐specific protein, the kappa immunoglobulin light chain (kappa) may play a role in the incidence of GVL and therefore the survival of transplant recipients following transplantation for B‐cell malignancies. Polymorphisms in the constant region of the immunoglobulin kappa polypeptide chain have been defined involving single amino acid changes at positions 153 and 191. In this study, 51 HLA‐matched B‐cell malignancy transplant pairs were kappa typed by polymerase chain reaction and restriction enzyme digestion to investigate the association between kappa allotype disparity and outcome after transplantation. Kappa allotype disparity between transplant pairs may be associated with an increased survival compared with pairs not mismatched for kappa, as kappa mismatched recipients had a higher percentage of complete remissions and a decreased level of relapse in comparison with the nonmismatched recipients. HLA peptide prediction software was used to determine which HLA types were the best binders for kappa peptides. It was observed that patients with tissue types predicted to bind the kappa Km(1,2) peptides had better survival outcomes and no relapse compared with those with tissue types not predicted to bind the kappa Km(1,2) peptides. This study may contribute to the assessment of the clinical role of kappa with regard to the outcome of allogeneic transplantation for B‐cell malignancies.
Trauma patients in the intensive care unit: short‐ and long‐term survival and predictors of 30‐day mortality
Authors: Ulvik A. , Wentzel‐Larsen T. , Flaatten H. 
Published: December 2006

Background:  The aims of this cohort study were to assess the survival of trauma patients treated in a general intensive care unit (ICU) and to evaluate the simplified acute physiology score (SAPS) II, maximum sequential organ failure assessment (SOFA) score, injury severity score (ISS), age, sex and severe head injury as predictors of 30‐day mortality.Methods:  Three hundred and twenty‐five adult patients admitted during 1998–2003 were evaluated retrospectively with update of survival data in January 2005. Kaplan–Meier statistics and Cox proportional hazards regression were used to study survival and to assess predictors of mortality, respectively.Results:  The 30‐day mortality was 16.9%, ICU mortality 13.8% and hospital mortality 17.8%. Long‐term survival (observation time, 1–7 years) was 77.8%. After 3.5 years, mortality was the same as for the background population. Severe head injury was the main cause of death and increased the risk of 30‐day mortality 2.4‐fold. In addition, SAPS II and an age above 50 years proved to be significant predictors of mortality in a multivariate analysis. Sex was not associated with mortality, and ISS and the maximum SOFA score were significant predictors in univariate analyses only.Conclusion:  Reduced long‐term survival was observed up to 3.5 years after acute injury. The 30‐day mortality was strongly related to severe head injury, SAPS II and an age above 50 years. These variables may be useful as predictors of mortality, and may contribute to risk adjustment of this subset of trauma patients when treatment results from different centres are compared.
Influence for testicular development and histological peculiarity in the testes of flutamide‐induced cryptorchid rat model
Authors: Mizuno Kentaro , Hayashi Yutaro , Kojima Yoshiyuki , Kurokawa Satoshi , Sasaki Shoichi , Kohri Kenjiro 
Published: December 2006

Objectives:  To investigate influence for the testicular development and to assess the usefulness as an animal model, cryptorchid rats were induced by exposure to flutamide during the fetal period and their testes examined histologically.Methods:  Flutamide was injected into the abdomen of pregnant rats for 7 days from the 14th to 20th day of gestation. The male offspring in which cryptorchidism was observed at 28 days after birth were defined as the model rats. They were divided into four groups by dosage of flutamide (2.5 mg, 5 mg, 7.5 mg, 15 mg per day), and their testicular weight, spermatogenesis (modified Johnsen score), and germ cell apoptosis were examined histochemically at 10 weeks after birth.Results:  The incidence of cryptorchidism including both unilateral and bilateral in the 2.5, 5, 7.5 and 15‐mg flutamide groups was 58.3%, 81.9%, 93.6% and 91.0%, respectively. In the model rats, the undescended testes were located at the caudal end of the abdominal cavity, and these testes weighed less than the contra‐descended testes in each group. Histologically, apoptotic cells were markedly increased, the seminiferous tubules were degenerated and disturbance of spermatid differentiation was observed in the undescended testes compared with the normal or contra‐lateral descended testes.Conclusions:  We found out that the incidence of undescended testes increased in a flutamide dose‐dependent manner. The findings of histological examination were independent of the administrated dose of flutamide and it is suggested that exposure of the testes to abdominal temperature causes spermatogenic arrest with germ cell apoptosis. The present animal model indicates high incidence of above 90%, has no surgical stress and dose not require special techniques. We believe that the present model is a useful tool for the understanding of pathogenesis and treatment of cryptorchidism and further biological research into spermatogenesis.
Long‐term results of first‐line sequential high‐dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor
Authors: Miki Tsuneharu , Mizutani Yoichi , Akaza Hideyuki , Ozono Seiichiro , Tsukamoto Taiji , Terachi Toshiro , Naito Katsusuke , Nonomura Norio , Hara Isao , Yoshida Osamu ,   The Japan Blood Cell Transplantation Study Group for Testicular Germ Cell Tumor
Published: December 2006

Objective:  Standard chemotherapy shows relatively low long‐term survival in patients with poor‐risk testicular germ cell tumor (GCT). First‐line high‐dose chemotherapy (HD‐CT) may improve the result. High‐dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first‐line chemotherapy in patients with advanced testicular GCT.Methods:  Fifty‐five previously untreated testicular GCT patients with Indiana ‘advanced disease’ criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD‐CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen.Results:  Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty‐five patients received BEP and HD‐CT. One patient died of rhabdomyolysis due to HD‐CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD‐CT achieved marker‐negative and marker‐positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow‐up time of 54 months. Severe toxicity included treatment‐related death (4%).Conclusions:  HD‐CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD‐CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first‐line chemotherapy for patients with poor‐risk testicular GCT.
System for simultaneous detection of 16 pathogens related to urethritis to diagnose mixed infection
Authors: Masue Naruyasu , Deguchi Takashi , Yokoi Shigeaki , Yamada Tohru , Ohkusu Kiyofumi , Ezaki Takayuki 
Published: December 2006

Objective:  Urethritis is not always caused by a single pathogen, and isolation of more than two pathogens from one patient is not uncommon. We developed a method to simultaneously detect 16 pathogens related to urethritis.Methods:  We designed specific primers used for amplification of urethritis pathogens in our 16‐well microplate assay. Sixteen microliters of each reaction mixture containing template DNA was added to each well to amplify 16 pathogens simultaneously.Results:  After we evaluated the specificity and sensitivity of this microplate polymerase chain reaction method, we used it to detect pathogens in clinical samples. Of 163 clinical samples, 49.7% (81/163) were positive for specific pathogens, and 6.7% (11/163) showed mixed infection. A specific pathogen was not identified in 43.6% (71/163) of cases.Conclusions:  We developed a 16‐well microplate assay with 16 specific primers to identify pathogens associated with urethritis.