bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Status of Genetic and Endocrine Factors in the Sex Change of Protandrous Black Porgy, Acanthopagrus schlegeli (Teleostean)
Authors: WU GUAN‐CHUNG , DU JIN‐LIEN , LEE YAN‐HORN , LEE MONG‐FONG , CHANG CHING‐FONG
Published: May 2005

Abstract: Black porgy, Acanthopagrus schlegeli Bleeker, a marine protandrous hermaphrodite fish, is functionally male for the first 2 years of life, but begins to sexually change to female after the third year. Testicular tissue and ovarian tissue are separated by connective tissue in the bisexual gonad. This sex pattern provides a unique model to study the mechanism of sex change in fish. The annual profiles of plasma estradiol, vitellogenin, and 11‐ketotestosterone concentrations in males were significantly different from those in the 3‐year‐old females. Oral administration of estradiol stimulated high levels of gonadal aromatase activity, plasma luteinizing hormone (LH) levels, and sex change in the 2‐year‐old fish. Oral administration with aromatase inhibitors for 1 year further blocked the natural sex change in 3‐year‐old black porgy and all fish became functional males. Transcripts of estrogen receptor (ER), androgen receptor, and gonadotropin receptors in the ovarian tissue of bisexual gonad were significantly less expressed than those in the bisexual testicular tissue. ER and aromatase transcripts were much higher in the vitellogenic ovary than those in the bisexual ovarian tissue. Plasma LH levels were higher in male fish than sex‐changing fish during postspawning and nonspawning season in 2+‐year‐old black porgy. We are also conducting investigations on the role of the genetic factors (Dmrt 1, Sox 9, Sf‐1, and Dax‐1) in sex development and sex change. An endocrine mechanism of sex change in black porgy is proposed.
Characterization of a Molt‐Inhibiting Hormone (MIH) Receptor in the Y‐Organ of the Kuruma Prawn, Marsupenaeus japonicus
Authors: ASAZUMA HIDEAKI , NAGATA SHINJI , KATAYAMA HIDEKAZU , OHIRA TSUYOSHI , NAGASAWA HIROMICHI
Published: May 2005

Abstract: To characterize a receptor for molt‐inhibiting hormone (MIH) in the kuruma prawn, Marsupenaeus japonicus, we performed a binding assay and chemical cross‐linking experiments using radiolabeled recombinant MIH ([125I]rMIH). The specific binding of [125I]rMIH was found in the membrane fraction of the Y‐organ (Kd= 4.76 × 10−10 M and Bmax= 5.51 × 10−12 M). Chemical cross‐linking between [125I]rMIH and the membrane fraction of the Y‐organ revealed that the MIH receptor protein has a molecular size of approximately 70 kDa.
Interaction of PCBs with Thyroid Hormone Levels and Time of Hatching in Chicken Embryos
Authors: BECK V. , ROELENS S A , MAERVOET J , SCHEPENS P , DARRAS V.M
Published: May 2005

Abstract: The effects of polychlorinated biphenyls (PCB 77, PCB 153, and the mixture Aroclor 1242) on circulating and intracellular thyroid hormone (TH) levels were studied during chicken embryonic development. We observed no influences of PCB 153 on TH availability. Aroclor 1242 caused a transient increase in the T3 level in the cerebellum at day 16. Clear effects were only seen with PCB 77 around the period of hatching: a severely reduced TH peak, which normally coincides with the stage of internal pipping, and a considerable delay in the moment of hatching.
Comparative Study of Family 2 GPCRs in Fugu rubripes
Authors: CARDOSO JOÃO , POWER DEBORAH , CLARK MELODY
Published: May 2005

Abstract: In this study, members of family 2 GPCRs, one of the largest families of receptors in vertebrates, were isolated and characterized in the genome of the Japanese pufferfish, Fugu rubripes, and compared with the orthologous genes in other vertebrates. Phylogenetic analysis carried out with all vertebrate family 2 GPCR members indicated that CALR/CGRPR and CRF are the most divergent receptor group within this family and that the remaining members appear to originate from a common ancestral gene precursor.
Are the Cannabinoids Involved in Bony Fish Reproduction?
Authors: COTTONE ERIKA , CAMPANTICO EZIO , GUASTALLA ALDA , ARAMU STEFANIA , POLZONETTI‐MAGNI ALBERTA M. , FRANZONI MARIAFOSCA
Published: May 2005

Abstract: Following the discovery of two CB1 genes in the fish Fugu rubripes, investigations on the phylogeny of endocannabinoids have indicated that this system is highly conserved. Our study demonstrated that CB1 receptors are expressed in the CNS and gonads of two teleosts, Carassius auratus and Pelvicachromis pulcher, and they show a high percentage of sequence identity with Fugu rubripes CB1A and Danio rerio CB1. By means of immunohistochemistry for CB1, sGnRH, and TH, we found a codistribution of these signaling molecules in the basal telencephalon/preoptic area, which are key centers for gonadotropic regulation. We therefore suggest that endocannabinoids are possibly involved in modulating fish reproduction at both the central and peripheral levels.
Upregulation of the Somatotropic Axis Is Correlated with Increased G6PDH Expression in Black Sea Bream Adapted to Iso‐osmotic Salinity
Authors: DEANE EDDIE E. , WOO NORMAN Y. S.
Published: May 2005

Abstract: Black sea bream (Mylio macrocephalus) were adapted to salinities of 0 ppt (freshwater), 6 ppt (hypo‐osmotic), 12 ppt (iso‐osmotic), 33 ppt (seawater), and 50 ppt (hypersaline) for 1 month. Using RT‐PCR assays, the expression of pituitary growth hormone (GH) and hepatic insulin‐like growth factor 1 (IGF‐1) genes were studied. It was found that the transcripts for both of these genes were highest in fish maintained at iso‐osmotic salinity. To correlate the expression of GH and IGF‐1 with an index of growth, we also measured the transcript levels of glucose‐6‐phosphate dehydrogenase (G6PDH) in liver. It was found that this transcript was also elevated in iso‐osmotically adapted black sea bream.
Seasonal Changes in the Activity of 11β‐Hydroxysteroid Dehydrogenase in Toad Testes
Authors: DENARI DANIELA , CEBALLOS NORA R.
Published: May 2005

Abstract: In mammals, glucocorticoids (GC) are inactivated by the oxidative activity of 11β‐hydroxysteroid dehydrogenase (11β‐HSD). To study that mechanism in the testes of Bufo arenarum, 11β‐HSD activity and plasma corticosterone (B) were determined in toads from pre‐ (PR), post‐ (P), and reproductive (R) periods. Toad 11β‐HSD is NAD+‐dependent and strongly inhibited by glycyrrhetinic acid. Vmax is higher in the P period (1.37 vs. R: 0.13 and PR: 0.26 pmol/min‐mg protein), whereas Km values (around 200 nM) remain constant. Plasma B concentrations (R: 178; PR: 61; P: 114 nM) are close to Km values, suggesting that, under baseline conditions, 11β‐HSD could protect testes against GC action.
Development of the Circadian Melatonin Rhythm and Its Responsiveness to PACAP in the Embryonic Chicken Pineal Gland
Authors: FALUHELYI N , REGLODI D , CSERNUS V
Published: May 2005

Abstract: The embryonic development of the circadian melatonin (MT) rhythm and the responsiveness of embryonic MT secretion to pituitary adenylate cyclase‐activating polypeptide (PACAP) were investigated. Using dynamic in vitro bioassays, we showed the following: (1) The circadian clock and/or the intracellular signal transduction pathways connecting the clock to the MT synthesizing apparatus appear between days 16 and 18 (E16‐18) of embryonic development. Lack of periodical environmental stimuli can lead to a delay in this maturation. (2) Exposure of the embryonic chicken pineal gland to PACAP induces a transitory increase in MT secretion and (3) a transitory increase in cyclic AMP efflux at or before day E13 in vitro.
Further Studies of Lipid Droplets in the Bombykol‐Producing Pheromone Gland of Bombyx mori
Authors: FÓNAGY ADRIEN , OHNISHI ATSUSHI , ESUMI YASUAKI , SUZUKI YOSHIKATSU , MATSUMOTO SHOGO
Published: May 2005

Abstract: Lipid droplets are abundant in the pheromone‐producing cells of B. mori at adult eclosion, followed by daily fluctuations in both their size and number. Their dynamics are related to PBAN‐stimulated de novo bombykol production. To elucidate associated events, we performed the following: (1) extraction, purification, and partial characterization of lipid droplet‐associated proteins found on their surface since their function could possibly be to transport and/or dock putative lipases that are responsible for the lipolysis of triglycerides in them; (2) separation, purification, and initial analysis of lipids carried by lipophorins and lipid transfer particles originating from pupal and adult hemolymph because of their role in the formation and accumulation of lipid droplets.
Pharmacological Characterization of Melanocortin Receptors in Fish Suggests an Important Role for ACTH
Authors: HAITINA TATJANA , KLOVINS JANIS , SCHIÖTH HELGI B.
Published: May 2005

Abstract: The melanocortin (MC) receptor subtypes have distinctive characteristic binding profiles. We found that the trout and Fugu MC4 receptors have similar affinity for α‐MSH and β‐MSH and a much higher affinity for ACTH than does the human MC4 receptor. The Fugu MC1 and the trout and Fugu MC5 receptors also have higher affinity for ACTH‐derived peptides than α‐, β‐, or γ‐MSH. It is tempting to speculate that ACTH‐derived peptides may have played an important role as “original” ligands at the MC receptors, while the specificity of the different subtypes for the α‐, β‐, and γ‐MSH peptides may have appeared at later stages during vertebrate evolution.
Measurement of PTHrP, PTHR1, and CaSR Expression Levels in Tissues of Sea Bream (Sparus aurata) Using Quantitative PCR
Authors: HANG X M , POWER D , FLIK G , BALMENT R J
Published: May 2005

Abstract: A quantitative PCR (Q‐PCR) method has been established to measure the mRNA expression levels of parathyroid hormone‐related protein (PTHrP), parathyroid hormone receptor type 1 (PTHR1), and calcium‐sensing receptor (CaSR) in sea bream (Sparus aurata), using the housekeeping gene, β‐actin, as endogenous control. TaqMan primers and probes were designed using the Primer Express program, according to the published/unpublished sequences of the three target genes and β‐actin of sea bream. Different tissues including gill, kidney, duodenum, hindgut, rectum, liver, heart, brain, pituitary, skin, muscle, and gonad were removed and immediately snap‐frozen from three juvenile sea bream (100‐150 g) cultured in sea water. The mRNAs were extracted and reverse‐transcribed into cDNAs, which were subsequently examined by the ABI 5700 system using an optimized Q‐PCR method. Triplicate measures of each sample indicated consistency of the technique. However, the mRNA expression levels for each transcript in these tissues were variable between fish and also relatively low. Nevertheless, this methodology can be used in the future studies of factors that may alter gene expression in these tissues.
Expression Analysis of Growth and Energy Regulation‐Associated Genes in Two Divergent Chicken Strains
Authors: KA SOJEONG , FITZSIMMONS CAROLYN , JACOBSSON LINA , SAVOLAINEN PETER , LUNDEBERG JOAKIM , SIEGEL PAUL B. , ANDERSSON LEIF , HALLBÖÖK F.NN
Published: May 2005

Abstract: We have studied differential expression of genes using cDNA arrays in the hypothalamic region of two divergent chicken lines, which differ in body weight and feeding behavior. Several transcripts from genes in metabolic networks as well as from retroviruses were differentially expressed.
Agouti‐Related Proteins (AGRPs) and Agouti‐Signaling Peptide (ASIP) in Fish and Chicken
Authors: KLOVINS JANIS , SCHIÖTH HELGI B.
Published: May 2005

Abstract: We performed an intensive search on sequence databases to identify orthologues of ASIP and AGRP peptides in a number of different species, revealing a number of genomic fragments coding for the C‐terminal part of agouti‐related motifs, different from annotated peptide sequences, including one fragment from chicken, two from zebrafish, two from Fugu (Takifugu rubripes), and three from Tetraodon (Tetraodon nigroviridis). We have thus shown for the first time that both AGRP and ASIP genes exist in many species in “lower vertebrates” and were most probably present in early stages of vertebrate evolution.
The Ancestry of the Prolactin‐Releasing Hormone Precursor
Authors: LAGERSTRÖM M C. , FREDRIKSSON R , BJARNADOTTIR T K. , SCHIÖTH H B.
Published: May 2005

Abstract: The prolactin‐releasing hormone (PRLH) is implicated in food intake and is expressed in several parts of the mammalian brain. The origin of the peptide precursor (PRH) has been unclear, and the only feature resembling other known human neuropeptide sequences is the C‐terminal RF‐motif, also present in the neuropeptide FF and the neuropeptide RF amide‐related peptide families (RFRP). We have recently found sequences of PRH and the closely related precursor C‐RF amide in chicken, shedding light on the PRH ancestry.
Pufferfish and Zebrafish Have Five Distinct NPY Receptor Subtypes, but Have Lost Appetite Receptors Y1 and Y5
Authors: LARSSON TOMAS A. , OLSSON FRIDA , SUNDSTRÖM GÖREL , BRENNER SYDNEY , VENKATESH BYRAPPA , LARHAMMAR DAN
Published: May 2005

Abstract: The two neuropeptide Y (NPY) receptors Y1 and Y5 stimulate feeding in mammals, but are missing in the euteleosts, zebrafish and pufferfish (Takifugu rubripes). Both species have five other subtypes called Y2, Y7, Ya, Yb, and Yc. RT‐PCR studies in pufferfish show that all five are expressed in the brain and may mediate NPY effects on feeding. Y2, Ya, and Yb are also broadly expressed in peripheral organs. These results reveal interesting differences in the NPY system of teleosts and mammals that may have arisen in the genetic turmoil involving the basal ray‐fin fish tetraploidization.
Effect of Cortisol on Aquaporin Expression in the Esophagus of the European Eel, Anguilla anguilla
Authors: MARTINEZ ANNE‐SOPHIE , WILSON GILLIAN , PHILLIPS CLAIRE , CUTLER CHRISTOPHER , HAZON NEIL , CRAMB GORDON
Published: May 2005

Abstract: Long‐term cortisol infusion into freshwater (FW)‐adapted eels induced a significant increase in aquaporin‐1 (AQP1) mRNA expression within the esophageal epithelium of migratory “silver” eels, but not in nonmigratory, immature “yellow” eels. Cortisol treatment had no significant effect on the mRNA abundance of a second aquaporin‐1 isoform, termed AQP1dup, which exhibited a highly variable expression profile among individual members of all fish groups. These results suggest that cortisol, at plasma concentrations similar to that found during FW/seawater (SW) acclimation, induces upregulation in AQP1 expression and thus increases esophageal water permeability during the migration of eels to the SW environment.
Successfully Determining the Sex of Adult Varanus mertensi (Reptilia: Varanidae) Using a Combination of Both Hemipenile Eversion and the Ratio of Androgens:Estradiol in Plasma
Authors: MAYES P.J , BRADSHAW S D , BRADSHAW F J
Published: May 2005

Abstract: In remote field localities, given limited access to specialized equipment, determining the sex of captured adult varanid lizards before release can be problematic. Determining the sex of the tropical semiaquatic Varanus mertensi, a species with significant tail musculature, is difficult using traditional hand‐pressure‐induced hemipenile eversion. As an alternative, we propose an extended technique for identifying the sex of adult V. mertensi. We recommend using a combination of the traditional field‐based hemipenile eversion technique and a measurement of the ratio of androgens to estradiol in plasma samples taken from field‐captured animals.
Genome Duplication‐Driven Evolution of Gene Families: Insights from the Formation of the Insulin Family
Authors: OLINSKI ROBERT PIOTR , LUNDIN LARS‐GUSTAV , HALLBÖÖK FINN
Published: May 2005

Abstract: The aim of this study was to outline the sequence of events that gave rise to the members of the insulin gene family in chordates. As part of our research, we looked for the chromosomal localization of insulin family members in the human genome.
Effects of a Teleost Tetraploidization on Neuropeptide Y Receptor Gene Repertoire in Ray‐Finned Fishes
Authors: SALANECK ERIK , LARSON EARL T. , LARSSON TOMAS A. , LARHAMMAR DAN
Published: May 2005

Abstract: The ancestral vertebrate repertoire for neuropeptide Y receptor genes of the Y1 subfamily probably included four subtypes: Y1, Y4, Y6, and Y8. There was probably a single gene in the Y5 category. Both Y1 and Y5 stimulate food intake in mammals. As the genome seems to have duplicated during the evolution of ray‐finned fishes, we have investigated the gene repertoire in species that diverged prior to the appearance of teleosts, as well as a basal teleost and a shark. Our results show that the genes Y1, Y5, and Y6, which are missing in many teleosts, are present in basal actinopterygians. These dramatic alterations of the teleost receptor repertoire may be related to the tetraploidization in a teleost ancestor.
Unusual Genomic Structure: Melanocortin Receptors in Fugu
Authors: SCHIÖTH HELGI B. , HAITINA TATJANA , FRIDMANIS DAVIDS , KLOVINS JANIS
Published: May 2005

Abstract: The melanocortin (MC) receptors are found in five subtypes in mammals and chicken, while recent studies have shown that the Fugu (Takifugu rubripes) genome has only four MC receptors and the zebrafish genome has six subtypes. The MC3 receptor seems to be missing from the two closely related pufferfishes, Fugu and Tetraodon (Tetraodon nigroviridis). The MC2 and MC5 receptors in the pufferfish have introns. Moreover, these two receptors are found in a tandem that is remarkably conserved in several vertebrate species. Here, we speculate about the genomic origin of the MC receptors.
Ray‐Fin Fish Tetraploidization Gave Rise to Pufferfish Duplicates of NPY and PYY, but Zebrafish NPY Duplicate Was Lost
Authors: SUNDSTRÖM GÖREL , LARSSON TOMAS A. , BRENNER SYDNEY , VENKATESH BYRAPPA , LARHAMMAR DAN
Published: May 2005

Abstract: We have used sequence information and gene location to identify NPY family genes in the pufferfish, Takifugu rubripes (fugu), and zebrafish. Fugu has two copies of NPY, presumably resulting from the ray‐fin fish tetraploidization. Zebrafish has probably lost one of the copies. Both species have two copies of PYY, the second of which was previously named PY. The two fugu NPY genes are predominantly expressed in brain. The two PYY genes are expressed in a broad range of tissues including brain and gonads. Thus, the NPY system appears to be more complex in teleosts than in tetrapods.
Linkage Mapping of the [Pro2]Somatostatin‐14 Gene in Zebrafish: Evolutionary Perspectives
Authors: TOSTIVINT HERVÉ , JOLY LUCILLE , LIHRMANN ISABELLE , CONLON J MICHAEL , EKKER MARC , VAUDRY HUBERT
Published: May 2005

Abstract: Radiation hybrid mapping assigned the zebrafish [Pro2]somatostatin‐14 (also termed somatostatin 2; SS2) gene to linkage group 23 of the zebrafish genome, close to the marker nadl1.2. Comparative genomic analysis revealed conserved syntenies of the SS2 gene locus with part of the human 1p36 region, where the cortistatin gene is located. This observation strongly suggests that the SS2 gene in nonmammalian species and the cortistatin gene in mammals are orthologous.
Differential Proteomics for Studying Drosophila Immunity
Authors: VIERSTRAETE EVY , VERLEYEN PETER , DE LOOF ARNOLD , SCHOOFS LILIANE
Published: May 2005

Abstract: Here, we report the identification of proteins associated with the immune response of Drosophila by analyzing the hemolymph profiles after infection. Two‐dimensional difference gel electrophoresis was used to study the secretome in the hemolymph of Drosophila larvae. Shortly after induction with lipopolysaccharides, we identified 10 proteins, which we designated ”Drosophila instantly released immune proteins”. Infection with Micrococcus luteus or Saccharomyces cerevisiae induced 20 and 19 differential protein spots, respectively. Next to known immune proteins, new candidates that require further investigation were identified.
Renal Morphology of the Euryhaline Flounder (Platichthys flesus): Distribution of Arginine Vasotocin Receptor
Authors: WEYBOURNE E , WARNE J M , HENTSCHEL H , ELGER M , BALMENT R J
Published: May 2005

Abstract: The current study characterized tubular segmentation of the European flounder nephron and localized the vasotocin receptor expression by immunohistochemistry. Flounder nephron was shown to comprise a prominent renal corpuscle, short neck segment, proximal tubule I, proximal tubule II, collecting tubule, and collecting duct. Using specific antibodies raised against flounder vasotocin receptor, specific V1 receptor staining was detected within the glomeruli, the endothelial surface of the afferent and efferent arterioles, and the capillaries surrounding the collecting duct system. Immunostaining for the receptor was exclusively vascular and there did not appear to be a tubular component.
Epidermal Growth Factor Receptor Inhibitors in the Treatment of Non–Small-Cell Lung Cancer
Authors: Giaccone Giuseppe
Published: May 2005

Remarkable developments in the systemic treatment of advanced non–small-cell lung cancer have taken place in the past few years. Targeted therapies have been largely employed in patients with far advanced disease, and some of them have demonstrated consistent activity in this setting. Epidermal growth factor receptor (EGFR) inhibitors cause dramatic response in approximately 10% of white patients who had received prior chemotherapy. Responses are higher in Asians. These findings are at least partly caused by the substantially higher incidence of EGFR mutations in Asians compared with whites. Studies of EGFR inhibitors in combination chemotherapy in front-line therapy of advanced non–small-cell lung cancer have, however, failed to improve survival, and better understanding of interactions between chemotherapeutic agents and EGFR inhibitors will be essential in the development of more effective strategies.
Epidermal Growth Factor Receptor Mutations in Non–Small-Cell Lung Cancer: Implications for Treatment and Tumor Biology
Authors: Jänne Pasi A. , Engelman Jeffrey A. , Johnson Bruce E.
Published: May 2005

The epidermal growth factor receptor (EGFR) has emerged as an attractive therapeutic target for patients with non–small-cell lung cancer (NSCLC). However, despite its almost universal presence in NSCLC tumors, therapeutic inhibition of EGFR has resulted in significant tumor regressions in only 10% to 20% of patients. Several investigations over the last 12 months have uncovered somatic mutations in EGFR that underlie the sensitivity to EGFR inhibitors. NSCLC tumors and cell lines with EGFR mutations are exquisitely sensitive to the EGFR tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib, and are biologically distinct from other forms of NSCLC. Somatic mutations in EGFR are found more frequently in patients with adenocarcinomas, nonsmokers, patients of Asian ethnicity, and in females. EGFR mutation detection is now becoming clinically available and is being incorporated into clinical treatment decisions and into the design of future clinical trials. Mutations in K-ras, a mediator of EGFR signaling, are mutually exclusive with EGFR mutations, and are associated with resistance to EGFR TKIs. In addition, secondary mutations, conferring resistance to EGFR TKIs, in patients with primary EGFR mutations once sensitive to EGFR TKIs, are beginning to be identified. The frequency of EGFR mutations, their impact on NSCLC biology, clinical treatment, and clinical trial design, as well as methods and limitations for mutation detection, will be reviewed.
AIDS-Related Burkitt's Lymphoma Versus Diffuse Large-Cell Lymphoma in the Pre–Highly Active Antiretroviral Therapy (HAART) and HAART Eras: Significant Differences in Survival With Standard Chemotherapy
Authors: Lim Soon Thye , Karim Roksana , Nathwani Bharat N. , Tulpule Anil , Espina Byron , Levine Alexandra M.
Published: May 2005

Purpose

To compare outcomes of patients with HIV-Burkitt's lymphoma (HIV-BL) and HIV-diffuse large-cell lymphoma (HIV-DLCL) after treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or M-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide) in pre–highly active antiretroviral therapy (HAART) versus HAART eras.

Patients and Methods

Three hundred sixty-three patients with AIDS-related lymphoma diagnosed from 1982 to 2003 were reviewed retrospectively, including 262 in the pre-HAART (HIV-BL, 117; HIV-DLCL, 145) and 101 in the HAART era (HIV-BL, 18; HIV-DLCL, 83). Pre-HAART included those who did not receive HAART, and HAART era included those diagnosed after January 1997 who received HAART.

Results

There were no significant differences between groups in terms of age, sex, history of injection drug use, prior AIDS, lactate dehydrogenase level, and disease stage at diagnosis. Compared with HIV-BL, HIV-DLCL was associated with significantly lower CD4 counts in the pre-HAART but not the HAART era. Although the overall median survival was similar for both groups in the pre-HAART era (HIV-BL, 6.4 months v HIV-DLCL, 8.3 months; P = .43), survival was significantly worse in patients with HIV-BL in the HAART era (HIV-BL, 5.7 months v HIV-DLCL, 43.2 months; P = .0003). Failure to attain complete remission and CD4 count less than 100 cells/mm3 independently predicted for poor survival in the pre-HAART era. In comparison, histology of HIV-BL and no attainment of complete remission were independent poor prognostic factors in the HAART era.

Conclusion

Survival of patients with HIV-DLCL has improved in the HAART era, along with CD4 count, whereas survival of similarly treated patients with HIV-BL remained poor. The current practice of using the same regimen for both groups of patients should be re-evaluated.
Phase II Study of Low-Dose Decitabine in Patients With Chronic Myelogenous Leukemia Resistant to Imatinib Mesylate
Authors: Issa Jean-Pierre J. , Gharibyan Vazganush , Cortes Jorge , Jelinek Jaroslav , Morris Gail , Verstovsek Srdan , Talpaz Moshe , Garcia-Manero Guillermo , Kantarjian Hagop M.
Published: May 2005

Purpose

To determine the activity of decitabine, a DNA methylation inhibitor, in imatinib-refractory or intolerant chronic myelogenous leukemia.

Materials and Methods

Thirty-five patients were enrolled in this phase II study (12 in chronic phase, 17 in accelerated phase, and six in blastic phase). Decitabine was administered at 15 mg/m2 intravenously over 1 hour daily, 5 days a week for 2 weeks. DNA methylation was measured using a LINE1 bisulfite/pyrosequencing assay.

Results

Complete hematologic responses were seen in 12 patients (34%) and partial hematologic responses in seven patients (20%), for an overall hematologic response rate of 54% (83% in chronic phase, 41% in accelerated phase, and 34% in blastic phase). Major cytogenetic responses were observed in six patients (17%), and minor cytogenetic responses were seen in 10 patients (29%) for an overall cytogenetic response rate of 46%. Median response duration was 3.5 months (range, 2 to 13+ months). Myelosuppression was the major adverse effect, with neutropenic fever in 28 (23%) of 124 courses of therapy. LINE1 methylation decreased from 71.3% ± 1.4% (mean ± standard error of the mean) to 60.7% ± 1.4% after 1 week, 50.9% ± 2.4% after 2 weeks, and returned to 66.5% ± 2.7% at recovery of counts (median, 46 days). LINE1 methylation at the end of week 1 did not correlate with subsequent responses. However, at day 12, the absolute decrease in methylation was 14.5% ± 3.0% versus 26.8% ± 2.7% in responders versus nonresponders (P = .007).

Conclusion

Decitabine induces hypomethylation and has clinical activity in imatinib refractory chronic myelogenous leukemia. We hypothesize that the inverse correlation between hypomethylation 2 weeks after therapy and response is due to a cell death mechanism of response, whereby resistant cells can withstand more hypomethylation.
Genomic and Proteomic Profiling of Lung Cancers: Lung Cancer Classification in the Age of Targeted Therapy
Authors: Meyerson Matthew , Carbone David
Published: May 2005

Both proteomic and genomic methods offer promise for the classification of human lung carcinomas. This review summarizes the range of proteomic methods in development for lung cancer classification, and describes a number of recent analyses of messenger RNA expression in lung cancer. Multiple independent studies of mRNA expression profiles in lung adenocarcinoma have proven highly reproducible. Analyses of the relationship between expression profiles and tumor development and differentiation, the presence or absence of specific pathogenic mutations, patient prognosis and survival after surgical treatment, and specific histopathology all appear to be promising.
Inositol-lipid binding motifs: signal integrators through protein-lipid and protein-protein interactions
Authors: Balla Tamas
Published: May 2005

Inositol lipids have emerged as universal lipid regulators of protein signaling complexes in defined membrane compartments. The number of protein modules that are known to recognise these membrane lipids is rapidly increasing. Pleckstrin homology domains, FYVE domains, PX domains, ENTH domains, CALM domains, PDZ domains, PTB domains and FERM domains are all inositide-recognition modules. The latest additions to this list are members of the clathrin adaptor protein and arrestin families. Initially, inositol lipids were believed to recruit signaling molecules to specific membrane compartments, but many of the domains clearly do not possess high enough affinity to act alone as localisation signals. Another important notion is that some (and probably most) of these protein modules also have protein binding partners, and their protein- and lipid-binding activities might influence one another through allosteric mechanisms. Comparison of the structural features of these domains not only reveals a high degree of conservation of their lipid interaction sites but also highlights their evolutionary link to protein modules known for protein-protein interactions. Protein-protein interactions involving lipid-binding domains could serve as the basis for phosphoinositide-induced conformational regulation of target proteins at biological membranes. Therefore, these modules function as crucially important signal integrators, which explains their involvement in a broad range of regulatory functions in eukaryotic cells.
Boundary-conformed machining of turbine blades
Authors: Ding S , Yang D C H , Han Z
Published: May 2005

Boundary-conformed machining is a new method to mill free-form surfaces with tool paths that reflect the natural shapes of the surfaces. It is suitable for the machining of turbine blades taking into account the direction of tool marks left on the vanes. To facilitate this type of machining, this paper introduces an application of the ‘boundary-conformed algorithm’ to generate continuous boundary-conformed flow line tool paths for the milling of blade surfaces. With this approach, the initial segment of the flow line tool paths is along the top edges of the blade while the final segment follows the intersection curves between the blade and the hub surface. The intermediate segments cover the surface by changing smoothly from the initial tool path to the final tool path. The two opposite sides of the blade, which are two trimmed surfaces, are machined together continuously from top to bottom with these continuous boundary-conformed tool paths. This method has been successfully integrated into an industrial computer-aided design and manufacture system (Pro/Engineer) by using Pro/Toolkit. A detailed algorithm and implementation processes have been introduced.
Primary chip formation during the micromachining of engineering materials
Authors: Jackson M J
Published: May 2005

The advent of nanotechnology has created a demand for precision-machined substrates so that ‘bottom-up’ nanomanufacturing processes can be used to produce functional products on the nanoscale. However, machining processes must be scaled down by an order of magnitude that requires very stable desktop machine tools to produce precision-machined substrates. Therefore, the mechanics of chip formation at this scale is critical when the effect is considered of chip formation on the generation of surface roughness on the substrate. The tight curl of a machined chip in orthogonal machining appears to be part of the primary shear process. It is also known that transient tight curl occurs before a secondary shear zone develops ahead of the removal of the chip from the cutting zone. However, continuum models predict that curled chips incorporate stresses due to the establishment of a secondary shear zone. A model is presented in terms of the heterogeneous aspects of continuous chip formation, which shows very good agreement with experimental data.
Film pressure distribution in water-lubricated rubber journal bearings
Authors: Cabrera D. L. , Woolley N. H. , Allanson D. R. , Tridimas Y. D.
Published: May 2005

Measurements of fluid film pressures were made on water-lubricated rubber journal bearings. The measurements indicated that the film pressure profiles are very different from those of conventional rigid bearings. The relatively low film pressures caused significant rubber deflections but were too low to produce lubricant viscosity changes. Integration of the pressure in the bearings showed that they operate in the regime of mixed lubrication. The behaviour of the bearings was theoretically investigated using computational fluid dynamics. There was reasonable agreement between computational fluid dynamics and experimental results.
Computer-aided design of hydrodynamic journal bearings considering thermal effects
Authors: Singh D. S. , Majumdar B. C.
Published: May 2005

A computer-aided design of hydrodynamic journal bearings is provided considering thermal effects. The Reynolds equation has been solved simultaneously along with the energy equation and heat conduction equations in bush and shaft to obtain the steady-state solution. Using the steady-state solution, a computer-aided design of such bearings is given. In this process, a data bank is generated that consists of load, friction factor and flow rate for different L/D and eccentricity ratios. These data are curve fitted to derive empirical relations for steady-state characteristics. These equations were then used in the design of such bearings. After designing the bearing, stability was checked using a linearized method.
Establishing a practical blood platelet threshold to avoid reporting spurious potassium results due to thrombocytosis
Authors: Thurlow V , Ozevlat H , Jones SA , Bailey IR
Published: May 2005

Background: Thrombocytosis is one of several pre-analytical factors which contribute to spuriously high serum potassium concentrations, yet there is little published data to guide analysts in the selection of a specific platelet count threshold above which serum potassium results become unreliable. We have studied the sensitivity and specificity of blood platelet count as a predictor of false elevations in potassium.

Methods: Paired serum and plasma potassium measurements together with full blood count were performed for 300 patients. All samples were stored at room temperature and analysed within 4 h of collection. The difference between serum and plasma potassium was plotted against blood platelet count.

Results: When the difference (serum-plasma) in potassium concentration was plotted against platelet count, there was a direct linear relationship. Blood platelet counts of >500 x 109/L will detect elevations in serum relative to plasma potassium of >0.5 mmol/L, with a sensitivity of 71% and a specificity of 89%.

Conclusion: It is recommended that where blood platelet count is above 500 x 109/L, potassium measurements should be repeated using lithium heparin plasma. When serum potassium results of >5.4 mmol/L are obtained, it is our policy to check the platelet count if a sample is available before reporting results. If available and above 500 x 109/L, potassium results are withheld and plasma requested.
Gitelman's syndrome presenting as intolerance to statin therapy
Authors: Freedman Danielle B , Housley David
Published: May 2005

Several factors predisposing patients to statin-induced myopathy have been described. We describe a patient whose statin intolerance was associated with changes in serum potassium arising from previously undiagnosed Gitelman's syndrome.
An innovative Australian point-of-care model for urine albumin: creatinine ratio testing that supports diabetes management in indigenous medical services and has international application
Authors: Shephard MDS , Gill JP
Published: May 2005

Background: Type 2 diabetes is the leading cause of end-stage renal failure in Australia's indigenous people. The measurement of urine albumin:creatinine ratio (ACR) as a marker for early renal disease is an important component of the management of indigenous patients with diabetes.

Methods: An innovative national program (Quality Assurance for Aboriginal Medical Services [QAAMS]) for point-of-care (POC) urine ACR testing on the DCA 2000 analyser (Bayer Diagnostics) was established to monitor microalbuminuria in indigenous people with diabetes in 30 Aboriginal and Torres Strait Islander medical services across Australia. Aboriginal health workers perform the ACR test. The QAAMS model provides ongoing education and training, an annual workshop, monthly quality assurance testing and a telephone help hotline. Quality assurance testing is conducted using paired, linearly related samples with a wide range of ACR concentrations (1-25 mg/mmol).

Results: The average participation rate across four six-monthly QAAMS ACR testing cycles was 83%. In all, 94% of 1163 quality assurance tests performed were within the preset limits of acceptability. The median precision (coefficient of variation percent for ACR quality assurance testing averaged 5.4%, well within desirable performance specifications. Between-site accuracy was excellent.

Conclusion: This unique POC model for supporting diabetes management is the first of its type to be developed for indigenous communities and has considerable potential to be adopted worldwide.
The British Society of Gastroenterology guidelines for the investigation of chronic diarrhoea, 2nd edition
Authors: Holbrook Ian
Published: May 2005

The prevalence of chronic diarrhoea has been estimated at 4-5% in Western populations and is one of the most common reasons for referral to a gastroenterological clinic. Investigation of patients was rationalized in 2003 with the publication by the British Society of Gastroenterology of guidelines for the investigation of chronic diarrhoea. The guidelines may also be viewed at www.bsg.org.uk/clinical_prac/guidelines/chronic_diarr.htm.
A simple method for the analysis of urinary sucralose for use in tests of intestinal permeability
Authors: Anderson A D G , Poon P , Greenway G M , MacFie J
Published: May 2005

Background: Sucralose is a unique disaccharide probe which is stable in the colon and can be used to assess permeability over the whole gut. Additional information can be gained when sucralose is administered in combination with lactulose and a monosaccharide such as L-rhamnose in the form of a 'triple sugar test.' We describe a simple assay for urinary sucralose by HPLC with refractive index detection (HPLC-RI).

Methods: Phenyl-β-D-glucopyranoside (internal standard) was added to 10 mL of urine, which was then passed through a 0.45 μm syringe filter. Elution was with 30% methanol (1 mL/min) on a reverse-phase C18 column. Detection was by refractive index, and integration based upon peak areas. Sixty standards of sucralose in human urine were analysed in order to quantify analytical variation.

Results: The standard curve for urinary sucralose was linear from 25 to 500 mg/L ( r>0.99). The limit of detection was 11 mg/L. Analytical recovery of sucralose at concentrations of 25, 50 and 100 mg/L was 101.5% (CV 7.59%), 102.9% (CV 5.82%) and 105.0% (CV 4.26%), respectively

Conclusions: The technique described represents a simple assay for urinary sucralose which performed with acceptable accuracy and precision and should facilitate the use of the triple sugar test in clinical research.
Centralized Pricing Versus Delegating Pricing to the Salesforce Under Information Asymmetry
Authors: Mishra Birendra K. , Prasad Ashutosh
Published: May 2005

The issue of delegating pricing responsibility to the salesforce is of interest to marketing academics and practitioners. It has been shown by Lal (1986) that under certain situations with information asymmetry, it is more profitable for the firm to delegate pricing authority to the salesforce than to have centralized pricing. In this paper we re-examine situations where information asymmetry exists and analyze its effect on the decision of the firm to set a price or delegate pricing responsibility to the salesforce. Using contract theory, we find that when the salesperson's private information can be revealed to the firm through contracting, centralized pricing performs at least as well as price delegation. We derive the optimal centralized pricing contract under a set of standard assumptions used in the economics and business literature.
Consumer Learning, Brand Loyalty, and Competition
Authors: Villas-Boas J. Miguel
Published: May 2005

In several markets, consumers can gain further information regarding how well a product fits their preferences only by experiencing it after purchase. This could then generate loyalty for the products tried first. This paper considers a model in which consumers learn in the first period about the product they buy and then make choices in the second period about the competing products, given what they learned in the first period. The paper finds that if the distribution of valuations for each product is negatively (positively) skewed, a firm benefits (is hurt) in the future from having a greater market share today—the brand loyalty characteristic. With negative skewness, two effects are identified: On one hand, marginal forward-looking consumers are less price sensitive than myopic consumers, and this is a force toward higher prices. On the other hand, forward-looking firms realize that they gain in the future from having a higher market share in the current period and compete more aggressively in prices. For similar discount factors for consumers and firms, the latter effect dominates. The paper also characterizes the importance of consumer learning effects on the market outcome.
A Dynamic Changepoint Model for New Product Sales Forecasting
Authors: Fader Peter S. , Hardie Bruce G. S. , Huang Chun-Yao
Published: May 2005

At the heart of a new product sales-forecasting model for consumer packaged goods is a multiple-event timing process. Even after controlling for the effects of time-varying marketing mix covariates, this timing process is not a stationary one, which means the standard interpurchase time models developed within the marketing literature are not suitable for new products.

In this paper, we develop a dynamic changepoint model that captures the underlying evolution of the buying behavior associated with the new product. This extends the basic changepoint framework, as used by a number of statisticians, by allowing the changepoint process itself to evolve over time. Additionally, this model nests a number of the standard multiple-event timing models considered in the marketing literature.

In our empirical analysis, we show that the dynamic changepoint model accurately tracks (and forecasts) the total sales curve as well as its trial and repeat components and other managerial diagnostics (e.g., percent of triers repeating).
Research Note—Cost Uncertainty Is Bliss: The Effect of Competition on the Acquisition of Cost Information for Pricing New Products
Authors: Christen Markus
Published: May 2005

We examine the optimal acquisition of information about a common uncertain cost factor by two competing firms seeking to price a new product. We show that existing findings regarding the acquisition of demand information or the acquisition of either cost or demand information related to quantity decisions do not extend to this case. For cost information with price competition, the information acquisition strategies are strategic substitutes, even though the price decisions that are based on the information are strategic complements. Competition decreases the expected value of cost information. Moreover, when competition is intense and the cost of information low, identical firms do not acquire the same amount of cost information—even when information is free. Cost uncertainty acts like a “fog” that lessens the destructive effect of price competition when products are close substitutes, and thus increases expected profits. Buyers, on the other hand, are better off when competing firms are informed about cost. Even though the expected value of cost information strictly decreases with competition, the optimal price for industry-specific cost information set by an information vendor increases with competition when the firms’ products are sufficiently substitutable.
The Corporate Digital Divide: Determinants of Internet Adoption
Authors: Forman Chris
Published: May 2005

The diffusion of Internet technology among firms is widely considered to be one of the primary factors behind the rapid economic growth of the 1990s. However, little systematic study has examined the variation in firm decisions to adopt the Internet. I explore the sources of this variation by examining Internet adoption decisions in a very large sample of organizations in the finance and services sector in 1998.

I show how prior information technology (IT) investments and workplace organization decisions affect the returns to adopting simple and complex Internet technologies. I show that recent investments in client/server (C/S) networking applications have competing effects on the likelihood of Internet adoption. Such investments can slow adoption by acting as a short-run substitute or by creating “switching costs.” Geographic dispersion of employees is complementary with Internet adoption, suggesting that Internet technology lowered internal coordination costs. Increases in organization size and external pressure also increase the likelihood of adoption.
Alcohol and gene interactions
Authors: Whitfield John B.
Published: May 2005

Alcohol use produces both desirable and undesirable effects, ranging from short-term euphoria and reduction in cardiovascular risk, to violence, accidents, dependence and liver disease. Outcomes are affected by the amount of alcohol used (which is itself affected by genetic variation) and also by the drinker's genes. Genetic effects have been most clearly demonstrated for alcohol dependence, and several of the genes for which variation leads to increased dependence risk have been identified. These include genes for enzymes involved in alcohol metabolism (alcohol dehydrogenase and aldehyde dehydrogenase), and genes for receptors affected by alcohol (particularly γ-aminobutyric acid receptors). Many other gene/dependence associations have been reported but not fully substantiated. Genetic effects on phenotypes other than alcohol dependence are less well understood, and need to be clarified before a full picture of gene-alcohol interactions can be achieved.
New Method to Determine the True Water Content of Organic Soils
Authors: O'Kelly BC
Published: May 2005

The true water content of organic soils is overestimated when the standard oven drying temperature of 110 ± 5°C is used due to some oxidation of the solids, and underestimated when the recommended oven drying temperature of 60°C is used due to some residual pore water remaining in the voids. A new method is presented to identify the precise oven drying temperature for which the mass of the residual pore water exactly balances the loss in the mass of solids due to oxidation. The true water content is calculated on the basis of the specimen dry mass recorded for this oven drying temperature.

A larger error arose when the water content of the test soil (70% organic content) was determined using the specimen dry mass recorded at 60°C rather than the standard drying temperature of 110 ± 5°C. Longer drying times were also required for the dry mass to equilibrate, making it more inconvenient from a practical standpoint. Some oxidation of the organic solids occurred for oven specimen drying above 80°C. The true value of the water content corresponded to an oven drying temperature of 86°C.