bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of CXCR4 and CXCL12 (SDF‐1) in human prostate cancers (PCa) in vivo
Authors: Sun Yan‐Xi , Wang Jingcheng , Shelburne Charles E. , Lopatin Dennis E. , Chinnaiyan Arul M. , Rubin Mark A. , Pienta Kenneth J. , Taichman Russell S. 
Published: May 2003

AbstractHuman prostate cancers (PCa) express great variability in their ability to metastasize to bone. The identification of molecules associated with aggressive phenotypes will help to define PCa subsets and will ultimately lead to better treatment strategies. The chemokine stromal‐derived factor‐1 (SDF‐1 or CXCL12) and its receptor CXCR4 are now known to modulate the migration and survival of an increasing array of normal and malignant cell types including breast, pancreatic cancers, glioblastomas, and others. The present investigation extends our previous investigations by determining the expression of CXCR4 and CXCL12 in humans using high‐density tissue microarrays constructed from clinical samples obtained from a cohort of over 600 patients. These data demonstrate that CXCR4 protein expression is significantly elevated in localized and metastastic cancers. At the RNA level, human PCa tumors also express CXCR4 and message, but overall, they were not significantly different suggesting post‐transcriptional regulation of the receptor plays a major role in regulating protein expression. Similar observations were made for CXCL12 message, but in this case more CXCL12 message was expressed by metastastic lesions as compared to normal tissues. PCa cell lines also express CXCL12 mRNA, and regulate mRNA expression in response to CXCL12 and secrete biologically active protein. Furthermore, neutralizing antibody to CXCL12 decreased the proliferation of bone homing LNCaP C4‐2B and PC3 metastastic tumor cells. These investigations provide important new information pertaining to the molecular basis of how tumors may ‘home’ to bone, and the mechanisms that may account for their growth in selected end organs. © 2003 Wiley‐Liss, Inc.
Identification of a domain within MDMX‐S that is responsible for its high affinity interaction with p53 and high‐level expression in mammalian cells
Authors: Rallapalli Ravikumar , Strachan Gordon , Tuan Rocky S. , Hall David J. 
Published: May 2003

AbstractThe MDMX gene product is related to the MDM2 oncoprotein, both of which interact with the p53 tumor suppressor. A novel transcript of the MDMX gene has been previously identified that has a short internal deletion of 68 base pairs, producing a shift in the reading frame after codon 114, resulting in the inclusion of 13 novel amino acids (after residue 114) followed by a stop codon at amino acid residue 127. This truncated MDMX protein, termed MDMX‐S, represents only the p53 binding domain and binds and inactivates p53 better than full‐length MDMX or MDM2. Here we show that when expressed in cells, MDMX‐S is targeted more efficiently to the nucleus than MDMX. MDMX‐S suppresses p53‐mediated transcription from a p53 target promoter better than full‐length MDMX. The DNA damage inducibility of these p53 responsive promoters was suppressed better by MDMX‐S than by MDMX. Analysis of the MDMX‐S protein indicated that the 13 novel amino acids at its carboxy terminus was responsible for high affinity binding to p53 in vitro and for high level expression of the protein in cells. Deletion of this 13 amino acid sequence resulted in a protein that was not able to bind p53 and was not able to be expressed well in cells. Taken together, these data point to an important domain within MDMX‐S that enables it to function well in vivo to block p53 activity. Published 2003 Wiley‐Liss, Inc.
Apoptotic effect of cleaved high molecular weight kininogen is regulated by extracellular matrix proteins
Authors: Guo Yan‐Lin , Wang Shujie , Cao Dian J. , Colman Robert W. 
Published: May 2003

AbstractWe previously reported that cleaved high molecular weight kininogen (HKa) and its domain 5 (D5) inhibit critical steps required for angiogenesis and in vivo neovascularization (Colman et al. 2000: Blood 95:543–550). We have further shown that D5 is able to induce apoptosis of endothelial cells, which may represent a critical part of the anti‐angiogenic activity of HKa and D5 (Guo et al. 2001: Arterioscler Thromb Vasc Biol 21:1427–1433). In this study, we demonstrate that HKa‐ and D5‐induced apoptosis is closely correlated with their anti‐adhesive effect. An important new finding is that the apoptotic activity of HKa and D5 is highly regulated by their interactions with different extracellular matrix (ECM) proteins. HKa inhibited cell adhesion to vitronectin (Vn, 90%) and gelatin (Gel) (40%), but it had no apparent effect on cell adhesion to fibronectin (Fn). D5 showed a similar pattern on cell adhesion but was less potent than HKa. HKa induced apoptosis of endothelial cells grown on Vn and Gel but not cells grown on Fn which closely parallels with its anti‐adhesive potency. Further results revealed that the anti‐adhesive effect and the apoptotic effect of HKa are associated with its ability to inhibit phosphorylation of focal adhesion kinase (FAK) and paxillin, two important signal molecules required for cell adhesion and cell viability. We conclude that the anti‐adhesive activity of HKa and D5 is responsible for their apoptotic effect and that Vn is likely an ECM component that mediates the effect of HKa and D5. © 2003 Wiley‐Liss, Inc.
Phytoestrogen genistein acts as an estrogen agonist on human osteoblastic cells through estrogen receptors α and β
Authors: Rickard D.J. , Monroe D.G. , Ruesink T.J. , Khosla S. , Riggs B.L. , Spelsberg T.C. 
Published: May 2003

AbstractGenistein, a soybean isoflavone, has estrogen‐like activity in mammals, including the prevention of bone loss. However, whether its mechanism of action on bone turnover is distinct from that of estrogen or raloxifene is unknown. Although genistein has been reported to bind both estrogen receptor (ER) isoforms (α and β), little is known concerning differential activation of gene expression via these ER isoforms. To examine this question, comparison of the responses of normal fetal osteoblast (hFOB) cells stably expressing either ERα (hFOB/ERα9) or ERβ (hFOB/ERβ6), to treatment with genistein, 17β‐estradiol (E2) or raloxifene were conducted. In hFOB/ERα9 cells, both genistein and E2 increased the endogenous gene expression of the progesterone receptor (PR), the proteoglycan versican, and alkaline phosphatase (AP), but inhibited osteopontin (OP) gene expression and interleukin‐6 (IL‐6) protein levels. Raloxifene had no effect on these bone markers. Genistein, but not raloxifene, also mimicked E2 action in the hFOB/ERβ6 cells increasing PR gene expression and inhibiting IL‐6 production. To determine whether the gene regulatory actions of genistein in human osteoblast cells occur at the level of transcription, its action on the transcriptional activity of a PR‐A promoter‐reporter construct was assessed. Both genistein and E2 were found to stimulate the PR promoter in the hFOB cell line when transiently co‐transfected with either ERα or ERβ. Whereas hFOB cell proliferation was unaffected by E2, raloxifene or genistein at low concentrations, higher concentrations of genistein, displayed significant inhibition. Together, these findings demonstrate that genistein behaves as a weak E2 agonist in osteoblasts and can utilize both ERα and ERβ. © 2003 Wiley‐Liss, Inc.
Impact on survivors of retinoblastoma when informed of study results on risk of second cancers
Authors: Schulz Charlene J. , Riddle Mary P. , Valdimirsdottir Heiddis B. , Abramson David H. , Sklar Charles A. 
Published: May 2003

AbstractBackgroundTo assess the impact of providing research feedback to retinoblastoma survivors or their parents regarding the risk of second cancers.ProcedureA four‐page survey was sent to 801 retinoblastoma survivors and 55 parents to ascertain their reactions to a “results‐letter.” The “results‐letter” provided feedback from a study indicating that retinoblastoma survivors may be at increased risk of second cancers.ResultsThree hundred and thirty‐nine (339) retinoblastoma survivors and 43 parents responded to the survey. Eighty‐four percent (84%) of respondents found the “results‐letter” “very” to “extremely” understandable and 72% found it “very” to “extremely” useful. Participants scored “very” to “extremely” to the following emotions: frightened = 28%, anxious = 27%, sad = 25%, overwhelmed = 15%, angry = 11%, and guilty = 6%. Five (1.4%) respondents stated that they would have preferred not to receive the results. Responses did not vary significantly between survivors with different risks of second cancers. No significant differences were observed between males and females. However, parents were significantly more likely to report feelings of anxiety, guilt, anger, being overwhelmed, and frightened compared to adult retinoblastoma survivors (P < 0.05). Individuals with less than a college education were significantly more sad, angry, overwhelmed, and frightened by the information than individuals with a college degree or higher (P < 0.05). Eighteen percent (18%) of all respondents shared the feedback with their physician. The method of choice for receiving results was by letter with contact names and phone numbers.ConclusionsThese findings indicate that research participants want feedback even when the information is upsetting. Additional studies are needed to identify individuals who experience greater levels of distress following feedback in an attempt to provide improved methods of feedback and support. Med Pediatr Oncol 2003;41:36–43. © 2003 Wiley‐Liss, Inc.
Computation of infinite integrals involving three Bessel functions by introduction of new formalism
Authors: Fabrikant V.I. 
Published: May 2003

AbstractIt has been accepted by many scientists, that whatever can be done in the field of evaluation of integrals of Bessel functions, had already been done, and that nothing new or important can be introduced at this stage. This article is written to disprove such a notion. Introduction of a new and elegant formalism not only allows simple computations of various integrals in terms of elementary functions, it also allows to discover errors (or misprints) in long standing results, which by now have entered practically all respectable tables of integrals.
Baseline personality functioning correlates with 6 month outcome in schizophrenia
Authors: Fassino Secondo , Pierò Andrea , Mongelli Elena , Caviglia Maria Luisa , Delsedime Nadia , Busso Federica , Gramaglia Carla , Abbate Daga Giovanni , Leombruni Paolo , Ferrero Andrea 
Published: May 2003

AbstractObjectiveThe assessment of outcome in schizophrenic patients should consider both the response to treatment and the recovery of social skills. The aim was to evaluate the outcome and related psychostructural and clinical factors in schizophrenic patients after they underwent 6 months of residential multimodal treatment.MethodsFifty-two schizophrenic patients enrolled in a multimodal treatment program were included in the study. Symptomatology and social functioning were assessed with the Brief Psychiatric Rating Scale (BPRS) and the Social and Occupational Functioning Assessment Scale (SOFAS). The Karolinska Psychodynamic Profile (KAPP) was used for the psychostructural evaluation.ResultsAfter 6 months there was a significant improvement in the global scores of BPRS, SOFAS, and some areas of KAPP. The personality (KAPP) and social-occupational functioning (SOFAS) at baseline (T0) correlated with the global score of BPRS at 6 months (T6); moreover, SOFAS at T6 correlated with BPRS and KAPP at T0 and with the illness duration.ConclusionsThe better the personality functioning in schizophrenic patients the better seems to be the response to treatment, with regard to symptoms as well as rehabilitation. Personality assessment might be useful for the individualisation of therapies, even within the context of a standardised program.
Recent evidence for dopamine abnormalities in schizophrenia
Authors: Abi-Dargham A. 
Published: May 2003

SummaryNeuroreceptor imaging has been used to examine dopamine function in schizophrenia. The evidence from PET and SPECT studies suggests that there is excess dopamine release subcortically, in the striatum, and that dopaminergic transmission may be abnormal in the cortex also, because of an upregulation in D1 receptors. We have found that patients with schizophrenia have higher subcortical levels of intrasynaptic dopamine (and have a greater proportion of D2 receptors occupied by dopamine) at baseline than controls. Those patients who had the highest levels of dopamine were the ones whose positive symptoms responded best to six weeks of treatment with an antipsychotic. Recent studies have also produced new evidence of dopaminergic disturbance in the cortex. When controls were compared with patients with schizophrenia, we found a significant increase in D1 receptors in patients, but only in the dorsolateral prefrontal cortex. Patients were also studied while they undertook a test of working memory. While there was no relationship between test performance and D1 binding potential for controls, those patients with the highest densities (most pathological levels) of D1 receptors performed the worst on the test. Both the D1 upregulation and the poor working memory may be secondary to a chronic, possibly neurodevelopmental deficit in dopamine innervation of the dorsolateral prefrontal cortex in schizophrenia. The D1 binding potential may prove to be a good biomarker with which to identify those patients suffering from schizophrenia who are most likely to benefit from treatment with a D1 agonist. A D1 receptor radiotracer that is sensitive to endogenous dopamine competition would be very valuable in the further exploration of this area.
The paper‐bill spread and real output: what matters more, a change in the paper rate or a change in the bill rate?
Authors: Ewing Bradley T , Lynch Gerald J , Payne James E 
Published: May 2003

AbstractThis paper adds to the literature on the information content of the paper‐bill spread by explicitly taking into account the two sources of wider spreads, rises in the paper rate and declines in the bill rate. Results from impulse response analysis and variance decompositions suggest that decreases in real output are greater and last longer when a widening of the paper‐bill spread comes from an increase in the paper rate rather than from an equivalent decrease in the bill rate. This is consistent with the idea that changes in the commercial paper rate have greater information content about future business cycles than do changes in the Treasury bill rate.
Compound heterozygosity of two missense mutations in the NADH‐cytochrome b5 reductase gene of a Polish patient with type I recessive congenital methaemoglobinaemia
Authors: Grabowska Dorota , Plochocka Danuta , Jablonska‐Skwiecinska Ewa , Chelstowska Anna , Lewandowska Irmina , Staniszewska Krystyna , Majewska Zofia , Witos Iwona , Burzynska Beata 
Published: May 2003

Abstract:A case of type I methaemoglobinaemia observed in a Polish subject with compound heterozygosity for two mutations in the reduced nicotinamide adenine dinucleotide (NADH) cytochrome b5 reductase (b5R) gene is described. One is a novel mutation 647T→C which leads to substitution of isoleucine by threonine at position 215 (I215T). This maternal mutation was found in several family members. A previously known mutation, 757G→A, leads to the replacement of valine by methionine at position 252 (V252M). The latter mutation was found also in the father and one of the two brothers. The effects of these mutations were analysed on a model of the human b5R protein obtained by homology modelling. Although both amino acid substitutions are located in the NADH‐binding domain, the whole protein structure, especially the region between the flavin adenine dinucleotide and NADH‐binding domains, is disturbed. The structural changes in the I215T mutant are less prominent than those in the V252M mutant. We presume that the 647T→C mutation is a type I mutation, however, it has not been observed in the homozygous state.
TYRP1 is associated with dun coat colour in Dexter cattle or how now brown cow?
Authors: Berryere T. G. , Schmutz S. M. , Schimpf R. J. , Cowan C. M. , Potter J. 
Published: May 2003

SummaryTyrosinase related protein 1 (TYRP1), which is involved in the coat colour pathway, was mapped to BTA8 between microsatellites BL1080 and BM4006, using a microsatellite in intron 5 of TYRP1. The complete coding sequence of bovine TYRP1 was determined from cDNA derived from skin biopsies of cattle with various colours. Sequence data from exons 2–8 from cattle with diluted phenotypes was compared with that from non‐diluted phenotypes. In addition, full‐sib families of beef cattle generated by embryo transfer and half‐sib families from traditional matings in which coat colour was segregating were used to correlate TYRP1 sequence variants with dilute coat colours. Two non‐conservative amino acid changes were detected in Simmental, Charolais and Galloway cattle but these polymorphisms were not associated with diluted shades of black or red, nor with the dun coat colour of Galloway cattle or the taupe brown colour of Braunvieh and Brown Swiss cattle. However, in Dexter cattle all 25 cattle with a dun brown coat colour were homozygous for a H424Y change. One Dexter that was also homozygous Y434 was red because of an ‘E+/E+’ genotype at MC1R which lead to the production of only phaeomelanin. None of the 70 remaining black or red Dexter cattle were homozygous for Y434. This tyrosine mutation was not found in any of the 121 cattle of other breeds that were examined.
Isolation and analysis of the non‐hydrolysable fraction of a forest soil and an arable soil (Lacadée, southwest France)
Authors: Poirier N. , Derenne S. , Balesdent J. , Mariotti A. , Massiot D. , Largeau C. 
Published: May 2003

SummaryRecent studies have pointed to the occurrence in soil organic matter of an insoluble macromolecular fraction, resistant to drastic alkali and acid hydrolysis. This non‐hydrolysable fraction may contribute to the stable carbon pool in the soil and thus be important for the global carbon budget. We have developed a method to isolate such chemically resistant components, whilst ensuring complete elimination of the hydrolysable constituents of the organic matter but avoiding the formation of insoluble compounds via Maillard‐type condensation reactions. Maize leaves, material especially susceptible to artefact formation, were used for this optimization. Several of the treatments that we tested, including the Klason lignin protocol, proved unsuitable. The most suitable protocol, by progressive hydrolysis with trifluoroacetic and hydrochloric acid, revealed a non‐hydrolysable fraction in maize leaves accounting for about 5% by weight of the leaves and corresponding chiefly to lignin and condensed tannins. The protocol was applied to a forest soil and to the soil from an adjacent plot cleared 35 years ago and since cropped continuously with maize. The abundance, chemical composition and sources of the non‐hydrolysable fraction of these two soils were determined by a combination of spectroscopy, pyrolysis and electron microscopy. This fraction accounted for about 6% of the total organic carbon of both soils; it contains aliphatic moieties, black carbon, melanoidins and, we think, condensed tannins.
Toxic effect of cadmium and nickel on soil enzymes and the influence of adding sewage sludge
Authors: Moreno J. L. , García C. , Hernández T. 
Published: May 2003

SummarySewage sludge is increasingly used as an organic amendment to soil, especially to soil containing little organic matter. However, little is known about the utility of this organic amendment in the reclamation of soil polluted with heavy metals. We studied the effects of adding sewage sludge on enzymatic activities of a semi‐arid soil contaminated with Cd or Ni in the laboratory. The activities of urease, phosphatase, β‐glucosidase and protease‐BAA were measured in soil containing concentrations of Cd or Ni in the range 0–8000 mg kg−1 soil, and their inhibition was compared with those of the enzymatic activities in the same soil amended with sewage sludge and containing similar concentrations of the heavy metals. The inhibition was tested for three different incubation times to determine changes in the effect of the heavy metals on hydrolase activity with the time elapsed after contamination. Ecological dose (ED) values of Cd and Ni were calculated from three mathematical models which described the inhibition of the enzymatic activities with increasing concentrations of heavy metal in the soil. For urease and phosphatase activities, the ED values for Cd and Ni increased after application of sewage sludge to soil, indicating a decrease in Cd and Ni toxicity. The other two enzymes (β‐glucosidase and protease‐BAA) were less sensitive to Cd or Ni contamination, and it was more difficult to determine whether addition of sewage sludge had affected the inhibition of these enzymes by the heavy metals.
Toxicity factors in acidic forest soils: attempts to evaluate separately the toxic effects of excessive Al3+ and H+ and insufficient Ca2+ and Mg2+ upon root elongation
Authors: Kinraide T. B. 
Published: May 2003

SummaryThe acidic soils of temperate forests and some pastures on former forest land characteristically contain large amounts of aluminium and hydrogen ions and small amounts of calcium and magnesium ions. The relative importance of these potential toxicity factors are assessed from published data from soils collected in the United States and Europe. Activities of ions in the soil solutions and at the surfaces of root‐cell plasma membranes were computed with electrostatic models. Activities of Al3+ in soil solutions ({Al3+}) peaked at pH 4.1, and Al3+ activities at the surface of the plasma membrane ({Al3+}0) achieved a broad maximum between pH 4.1 and 4.8; thus, Al3+ intoxication is likely to be more severe in soils at pH 4.1 than in more acidic ones. Intoxication (assessed by root elongation) correlated somewhat ambiguously with ion activities, but Al3+‐ and H+‐induced depletion of Ca2+ and Mg2+, or both, from the cell surface appears to play a role in toxicity. By contrast, experiments in solution culture, where intercorrelation among {Al3+}, {H+}, and {Ca2+} could be avoided, clearly demonstrated the following extrinsic and intrinsic effects. 1 The ions Al3+ and H+ are intrinsic toxicants. 2 They are also extrinsic toxicants because of the electrostatic displacement of Ca2+ from the surface of the plasma membrane. 3 They are extrinsic ameliorants because each electrostatically displaces the other from the surface of the plasma membrane. 4 The ion Ca2+ is an extrinsic ameliorant because of the electrostatic displacement of Al3+ and H+ from the surface of the plasma membrane. 5 It is an intrinsic ameliorant of intrinsic H+ toxicity, but not intrinsic Al3+ toxicity. 6 It meets an intrinsic requirement. 7 The ion Mg2+ resembles Ca2+ in item 4 but not items 5 and 6 in short‐term cultures.In acidic soils, Al3+ may prevent H+ from becoming an intrinsic toxicant (item 3) and may induce an insufficiency of Ca2+ and Mg2+ (item 2). These findings have implications for the mechanisms by which woodland plants tolerate very acidic soils.