bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pleiotrophin expression correlates with melanocytic tumor progression and metastatic potential
Authors: Wu H. , Barusevicius A. , Babb J. , Klein‐Szanto A. , Godwin A. , Elenitsas R. , Gelfand J. M. , Lessin S. , Seykora J. T. 
Published: December 2004

Background:  Gene expression profiling of melanoma and nevic tissue has demonstrated that pleiotrophin (PTN) is significantly overexpressed in human melanomas.Methods:  To further evaluate PTN expression in melanocytic lesions, protein immunohistochemistry was performed on the spectrum of melanocytic lesions.Results:  Melanocytic nevi were consistently negative (n = 58). In contrast, the great majority of metastatic melanomas were positive (33/34, 97%). The analysis of 34 primary melanomas demonstrated PTN positivity in 20 lesions while 14 lesions were negative. Within the primary melanomas, PTN immunoreactivity was associated with metastasis (p = 0.0004) and decreased melanoma‐related survival (p = 0.0444). Univariate analysis of PTN immunoreactivity predicted an increased risk for metastasis (relative risk 9.1, p = 0.003).Conclusions:  The results of this study confirm previous gene profiling data showing differential PTN expression between melanocytic nevi and melanomas. In addition, lesional PTN expression is associated with metastatic potential and may be a prognostic factor for melanomas.
bdrF
2

of Lyme Disease Spirochetes Is Coexpressed with a Series of Cytoplasmic Proteins and Is Produced Specifically during Early Infection
Authors: Zhang Hongming , Raji Abayami , Theisen Michael , Hansen Paul R. , Marconi Richard T. 
Published: December 2004

ABSTRACT

The Bdr proteins are polymorphic inner membrane proteins produced by most
Borrelia
species. In
Borrelia burgdorferi
B31MI, the18
bdr
genes form three subfamilies,
bdrD
,
bdrE
, and
bdrF
. The production of at least one of the Bdr paralogs, BdrF
2
, is up-regulated in host-adapted spirochetes, suggesting a role for the protein in the mammalian environment. Here, we demonstrate using reverse transcriptase (RT) PCR that BBG29, BBG30, BBG31, and BBG32, which reside upstream of

bdrF
2

, are cotranscribed with

bdrF
2

as a five-gene operon. While the functions of most of these proteins are unknown, BBG32 encodes a putative DNA helicase. Real-time RT-PCR analyses demonstrated higher levels of

bdrF
2

transcript relative to other genes of the operon, suggesting that

bdrF
2

may also be transcribed independently from an internal promoter. Internal promoters were detected using the 5′ rapid amplification of cDNA ends system. The putative promoter associated with

bdrF
2

was found to be highly similar in sequence to the multiple promoters associated with the
ospC
gene. Real-time RT-PCR analyses, performed to assess the expression of these genes in infected mice, revealed that genes of the

bdrF
2

locus are expressed only during early infection, suggesting a role in the establishment of infection. To further characterize the proteins encoded by the

bdrF
2

locus, which have unknown functions, the cellular localizations of these proteins were determined by Triton X-114 extraction and phase partitioning. BBG29 and BBG31 were found to be cytoplasmic. To determine if these proteins elicit an antibody (Ab) response during infection, immunoblot analyses were performed. Abs to these proteins were not detected. Based on the analyses presented here, we offer the hypothesis that BdrF
2
and other proteins encoded by the operon form an inner-membrane-associated protein complex that may interact with DNA and which carries out its functional role during transmission or the early stages of infection.
Intersubunit Complementation of Sugar Signal Transduction in VirA Heterodimers and Posttranslational Regulation of VirA Activity inAgrobacterium tumefaciens
Authors: Wise Arlene A. , Voinov Luba , Binns Andrew N. 
Published: December 2004

ABSTRACTThe VirA/VirG two-component regulatory system ofAgrobacterium tumefaciensregulates expression of the virulence (vir) genes that control the infection process leading to crown gall tumor disease on susceptible plants. VirA, a membrane-bound homodimer, initiatesvirgene induction by communicating the presence of molecular signals found at the site of a plant wound through phosphorylation of VirG. Inducing signals include phenols, monosaccharides, and acidic pH. While sugars are not essential for gene induction, their presence greatly increasesvirgene expression when levels of the essential phenolic signal are low. Reception of the sugar signal depends on a direct interaction between ChvE, a sugar-binding protein, and VirA. Here we show that the sugar signal received in the periplasmic region of one subunit within a VirA heterodimer can enhance the kinase function of the second subunit. However, sugar enhancement ofvirgene expression was vector dependent.virAalleles expressed from pSa-derived vectors inhibited signal transduction by endogenous VirA. Inhibition was conditional, depending on the induction medium and thevirAallele tested. Moreover, constitutive expression ofvirGovercame the inhibitory effect of some but not allvirAalleles, suggesting that there may be more than one inhibitory mechanism.
Methionine Sulfoxide Reduction and Assimilation in
Escherichia coli
: New Role for the Biotin Sulfoxide Reductase BisC
Authors: Ezraty Benjamin , Bos Julia , Barras Frédéric , Aussel Laurent 
Published: December 2004

ABSTRACT

Methionine ranks among the amino acids most sensitive to oxidation, which converts it to a racemic mixture of methionine-
S
-sulfoxide (Met-S-SO) and methionine-
R
-sulfoxide (Met-R-SO). The methionine sulfoxide reductases MsrA and MsrB reduce free and protein-bound MetSO, MsrA being specific for Met-S-SO and MsrB for Met-R-SO. In the present study, we report that an

Escherichia coli metB
1

auxotroph lacking both
msrA
and
msrB
is still able to use either of the two MetSO enantiomers. This indicates that additional methionine sulfoxide reductase activities occur in
E. coli
. BisC, a poorly characterized biotin sulfoxide reductase, was identified as one of these new methionine sulfoxide reductases. BisC was purified and found to exhibit reductase activity with free Met-S-SO but not with free Met-R-SO as a substrate. Moreover, a

metB
1
msrA msrB bisC

strain of
E. coli
was unable to use Met-S-SO for growth, but it retained the ability to use Met-R-SO. Mass spectrometric analyses indicated that BisC is unable to reduce protein-bound Met-S-SO. Hence, this study shows that BisC has an essential role in assimilation of oxidized methionines. Moreover, this work provides the first example of an enzyme that reduces free MetSO while having no activity on peptide-bound MetSO residues.
Regulation of Uptake and Processing of the Quorum-Sensing Autoinducer AI-2 inEscherichia coli
Authors: Xavier Karina B. , Bassler Bonnie L. 
Published: December 2004

ABSTRACTAI-2 is a quorum-sensing signaling molecule proposed to be involved in interspecies communication. InEscherichia coliandSalmonella entericaserovar Typhimurium, extracellular AI-2 accumulates in exponential phase, but the amount decreases drastically upon entry into stationary phase. InS. entericaserovar Typhimurium, the reduction in activity is due to import and processing of AI-2 by the Lsr transporter. We show that the Lsr transporter is functional inE. coli, and screening for mutants defective in AI-2 internalization revealedlsrKandglpD. Unlike the wild type,lsrKandglpDmutants do not activate transcription of thelsroperon in response to AI-2.lsrKencodes the AI-2 kinase, and thelsrKmutant fails to activatelsrexpression because it cannot produce phospho-AI-2, which is thelsroperon inducer.glpDencodes the glycerol-3-phosphate (G3P) dehydrogenase, which is involved in glycerol and G3P metabolism. G3P accumulates in theglpDmutant and represseslsrtranscription by preventing cyclic AMP (cAMP)-catabolite activator protein (CAP)-dependent activation. Dihydroxyacetone phosphate (DHAP) also accumulates in theglpDmutant, and DHAP represseslsrtranscription by a cAMP-CAP-independent mechanism involving LsrR, thelsroperon repressor. The requirement for cAMP-CAP inlsractivation explains why AI-2 persists in culture fluids of bacteria grown in media containing sugars that cause catabolite repression. These findings show that, depending on the prevailing growth conditions, the amount of time that the AI-2 signal is present and, in turn, the time that a given community of bacteria remains exposed to this signal can vary greatly.
The Mrp Na
+
/H
+
Antiporter Increases the Activity of the Malate:Quinone Oxidoreductase of an
Escherichia coli
Respiratory Mutant
Authors: Swartz Talia H. , Ito Masahiro , Hicks David B. , Nuqui Mark , Guffanti Arthur A. , Krulwich Terry A. 
Published: December 2004

ABSTRACT

Mrp catalyzes secondary Na
+
/H
+
antiport and was hypothesized to have an additional primary energization mode. Mrp-dependent complementation of nonfermentative growth of an
Escherichia coli
respiratory mutant supported this hypothesis but is shown here to be related to increased expression of host malate:quinone oxidoreductase, not to catalytic activity of Mrp.
Assimilation of Nitrogen from Nitrite and Trinitrotoluene in
Pseudomonas putida
JLR11
Authors: Caballero Antonio , Esteve-Núñez Abraham , Zylstra Gerben J. , Ramos Juan L. 
Published: December 2004

ABSTRACT

Pseudomonas putida
JLR11 releases nitrogen from the 2,4,6-trinitrotoluene (TNT) ring as nitrite or ammonium. These processes can occur simultaneously, as shown by the observation that a
nasB
mutant impaired in the reduction of nitrite to ammonium grew at a slower rate than the parental strain. Nitrogen from TNT is assimilated via the glutamine syntethase-glutamate synthase (GS-GOGAT) pathway, as evidenced by the inability of GOGAT mutants to use TNT. This pathway is also used to assimilate ammonium from reduced nitrate and nitrite. Three mutants that had insertions in
ntrC
,
nasT
, and
cnmA
, which encode regulatory proteins, failed to grow on nitrite but grew on TNT, although slower than the wild type.
Can You Teach Environmental Philosophy Without Being an Environmentalist?
Authors: de Laplante Kevin 
Published: December 2004

AbstractThe orthodox conception of environmental philosophy is of an applied or practical philosophical discipline in the service of the ethical, social and political aims of the environmental movement. In this essay I show that there is a coherent alternative conception of the subject matter of environmental philosophy—what I call an "ecological" conception—that can be defined independently of environmentalist concerns. I argue that, as a framework for advancing both the theoretical and applied aims of environmental philosophy, the ecological conception of environmental philosophy has a number of advantages over the orthodox conception. I conclude with some remarks on the implications of adopting the ecological conception for teaching courses in environmental philosophy.
Teaching Environmental Ethics To Non-specialist Students
Authors: Mason Hugh 
Published: December 2004

AbstractThis paper outlines an approach to teaching environmental ethics to non-specialist students. The use of a "problem-solving" approach to ethical dilemmas is advocated as the most suitable vehicle for addressing the needs of non-specialists. This approach commences with a consideration of the existence of ethical dilemmas and of the different values that can account for the problems being contested. The approach then addresses the various methods by which such dilemmas can be appreciated and understood if not completely solved, drawing not merely on environmental ethics work but on approaches in cognate areas.
The African National Congress' Economic and Social Policy Changes in South Africa (1994-2004): Another African Straightjacket Independence?
Authors: wa Muiu Mueni 
Published: December 2004

AbstractIn this article I argue that Liberal democracy in South Africa accommodated and left unresolved the contradictions of South African capitalism and the ANC's multiracial nationalist discourse. More specifically, the delivery of equal political rights in the new democracy is premised on the acceptance of the unequal economic relations among different classes, gender and race. Second, the multi-racial and multi-ethnic middle class is threatened from above and below. Popular demands from below sometimes lead it to partially satisfy the people's economic and social demands. Pressure from economic interests and the business community limits the middle class' room for maneuver and forces it to make compromises at the expense of the people's interests, priorities and needs (especially economic ones). Apartheid's inequality can only be addressed by a radical program based on the majority's economic and social needs. Liberal democracy does not allow for radical changes because it privileges the market rather than peoples' needs. Consequently, the ANC cannot meet its overseers' (business, bilateral institutions, white minority) interests as well as transform the economy. These realities will continue to inform ANC's economic and social policies as it tries to transform South Africa for the foreseeable future.
Temporal Acculturation and Mental Health in Modern Ireland
Authors: MacLachlan Malcolm , Smyth Caroline , Breen Fiona , Madden Tonya 
Published: December 2004

Background: Research on geographic acculturation has demonstrated an association between the sort of acculturation strategy adopted by migrants and their mental health status. However, there have been no studies of the relationship between temporal acculturation - attempts to adapt to change within the same society over time - and mental health. Method: We explored the relevance of Berry’s bidimensional framework of acculturation, to perceptions of social change within Ireland over the last 10 years, in a sample of 735 members of the general public. Results: There was a significant relationship between temporal acculturation strategy and mental health. An acculturation strategy of assimilating into ‘modern’ Ireland was associated with significantly better mental health than an ambivalent acculturation strategy. Conclusions: This is a first exploration of the relationship between temporal acculturation and mental health. While models of geographic acculturation are relevant to temporal acculturation, we have also identified a new category of acculturation strategy, ambivalence, as being associated with the poorest mental health outcomes.
Angiogenesis Inhibitor IM862 Is Ineffective Against AIDS-Kaposi's Sarcoma in a Phase III Trial, but Demonstrates Sustained, Potent Effect of Highly Active Antiretroviral Therapy: From the AIDS Malignancy Consortium and IM862 Study Team
Authors: Noy Ariela , Scadden David T. , Lee Jeannette , Dezube Bruce J. , Aboulafia David , Tulpule Anil , Walmsley Sharon , Gill Parkash 
Published: December 2004

Purpose IM862 is a synthetic dipeptide (l-glutamine l-tryptophan) with in vitro and in vivo antiangiogenic properties. Phase I/II studies showed minimal toxicity and a response rate of 36% in AIDS-Kaposi's sarcoma. We report a 24-week, randomized, double-blinded, placebo-controlled phase III trial with the phase II dose, 5 mg intranasally every other day. Patients and Methods Two hundred two HIV-positive patients were enrolled, 104 on IM862 and 98 on placebo. Results Baseline characteristics were comparable except current antiretroviral therapy: 88% versus 96% (IM862 v placebo group; P = .042). The median treatment durations were 19.5 versus 24 weeks (IM862 v placebo). No significant difference was detected in response rate (IM862, 23%; 95% CI, 15% to 32% v placebo, 21%; 95% CI, 14% to 31%; P = .46), time to response (8.5 weeks v 14 weeks; P = .024), or duration of response. However, IM862 was associated with both a shorter time to response (8.5 weeks v 14 weeks; P = .024) and shorter median time to progression (16 weeks, 95% CI, 13 to 27 weeks v 35 weeks, 95% CI, 26 to 114 weeks; P = .012). Conclusion Despite promising phase I and phase II studies, IM862 5 mg every other day was not superior to placebo and may accelerate time to progression. Highly active antiretroviral therapy alone was associated with a substantial rate of sustained tumor response and may have contributed to prior estimates of IM862 response. Therapeutic trials for AIDS-Kaposi's sarcoma must account for ongoing immune reconstitution in the setting of concurrent highly active antiretroviral therapy that may confound estimates of therapeutic activity.
Comparison of the binding affinity of some newly synthesized phenylethanolamine and phenoxypropanolamine compounds at recombinant human β- and α1-adrenoceptor subtypes
Authors: Ahmed Maruf , Hanaoka Yoko , Kiso Tatsuya , Kakita Takao , Ohtsubo Yoshikazu , Muramatsu Ikunobu , Nagatomo Takafumi 
Published: December 2004

Abstract
We evaluated six new compounds, SWR-0065HA ([4-[2-[3-[[(3,4-dihydro-4-oxo-[1,2,4]-triazino(4,5-a)indol)-lyl]oxy]-2-hydroxypropylamino]ethoxy]phenyl]acetic acid methyl ester hydrochloride), SWR-0098NA ((R*R*-UE)-(E)-[4-[3-[(2-phenyl-2-hydroxyethyl)amino]-1-butenyl]phenoxy]acetic acid sodium salt), SWR-0315NA ((E, Z)-[4[[1-[2-[(3-phenoxy-2-hydroxy propyl)]amino]ethyl]-1-propenyl]phenoxy]acetic acid sodium), SWR-0338SA ((E)-[4-[5-[(2-phenyl-2-hydroxyethyl)amino]-2-pentene-3-yl]phenoxy] acetic acid ethanedioic acid), SWR-0342SA ((S)-(Z)-[4-[[1-[2-[(2-hydroxy-3-phenoxypropyl)]amino] ethyl]-1-propenyl]phenoxy]acetic acid ethanedioic acid) and SWR-0345HA ((E)-2-methyl-3-[4-[2-(2-phenyl-2-hydroxyethylamino)ethoxy]phenyl]-2-propenoic acid ethyl ester hydrochloride) for their potencies as selective ligands at human β-adrenoceptors expressed in COS-7 cells and compared the binding affinities for human α1-adrenoceptors expressed in Chinese hamster ovary (CHO) cells using a radioligand-binding assay. Phenoxypropanolamine derivatives SWR-0315NA and SWR-0342SA showed higher binding affinities for β-adrenoceptor subtypes; SWR-0065HA, however, showed a higher affinity for only β2-adrenoceptors, accounting for 3-fold and 6-fold selectivity against β1- and β3-adrenoceptors. Compounds SWR-0315NA and SWR-0342SA did not show any binding selectivity for any of the subtypes. However, functionally these two compounds are selective for β3-adrenoceptors. Among the phenylethanolamine derivatives, SWR-0338SA and SWR-0345HA showed 9-fold and 16-fold higher binding selectivity for β3-adrenoceptors against β1-adrenoceptors, respectively, whereas they both showed a 7-fold higher binding selectivity for β3-adrenoceptors against β2-adrenoceptors. SWR-0098NA did not show any significant binding affinity for any of the β-adrenoceptor subtypes. These compounds, except for SWR-0098NA, were not found to possess any significant binding affinity for α1-adrenoceptor subtypes over that for β-adrenoceptor subtypes. However, SWR-0098NA has about a 3-fold to 22-fold higher binding selectivity for α1-adrenoceptor subtypes against β-adrenoceptor subtypes, making it difficult for use in a β-adrenoceptor receptor study. Compounds SWR-0315NA and SWR-0342SA have similar binding potency for α1-adrenoceptors as adrenaline (epinephrine), proving the finding of this manuscript that this phenoxypropanolamine group of β-adrenoceptor ligands could also be used as α1-adrenoceptor ligands. Functional assays have to be performed to confirm their agonistic activity.
Kanamycin incorporation in lipid vesicles prepared by ethanol injection designed for tuberculosis treatment
Authors: Justo Oselys Rodriguez , Moraes Angela Maria 
Published: December 2004

Abstract
The primary goal of this study was the production of liposomes encapsulating kanamycin for drug administration by inhalation. The selected drug is indicated for multiresistant tuberculosis, and administration through inhalation allows both local delivery of the drug to the lungs and systemic therapy. The ethanol injection method used for the liposome production is easily scaled up and is characterized by simplicity and low cost. Vesicles were prepared using different lipid compositions, including hydrogenated soybean phosphatidylcholine and cholesterol (SPC/Chol), egg phosphatidylcholine and cholesterol (EPC/Chol), distearoyl phosphatidylcholine and cholesterol (DSPC/Chol), distearoyl phosphatidylcholine, dimyristoyl phosphatidylethanolamine and cholesterol (DSPC/DMPE/Chol), dipalmitoyl phosphatidylcholine and cholesterol (DPPC/Chol) and dipalmitoyl phosphatidylcholine, dipalmitoyl phosphatidylglycerol and cholesterol (DPPC/DPPG/Chol). The effects of different operational conditions for vesicle production and drug encapsulation were evaluated, aiming at a compromise between final process cost and suitable vesicle characteristics. The best performance concerning drug incorporation was achieved with the DSPC/Chol system, although its production cost was considerably larger than that of the natural lipids formulations. Encapsulation efficiencies up to 63% and final drug to lipid molar ratios up to 0.1 were obtained for SPC/Chol vesicles presenting mean diameters of 132 nm incubated at 60°C with the drug for 60 min at an initial drug-to-lipid molar ratio of 0.16.
Loperamide inhibits the biliary excretion of irinotecan (CPT-11) in the rat isolated perfused liver
Authors: Tobin Peter J , Hong Ying , Seale J Paul , Rivory Laurent P , McLachlan Andrew J 
Published: December 2004

Abstract
Patients treated with irinotecan (CPT-11) occasionally suffer from severe diarrhoea and aggressive treatment with loperamide at the first signs of loose stools is recommended. We have examined the effect of loperamide on the hepatic metabolism and biliary excretion of CPT-11 in the isolated perfused rat liver (IPRL). CPT-11 (0.5 μmol) was injected as a bolus into the IPRL reservoir, and perfusate and bile samples were collected over 3h. Experiments were conducted using loperamide-free perfusate (n = 5) or perfusate containing 10 μm loperamide (n = 6). Perfusate and bile concentrations of total CPT-11 and the major metabolites SN-38 (7-ethyl-10-hydroxy-camptothecin), SN-38G (7-ethyl-10-hydroxy-camptothecin glucuronide) and APC (7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidine] carbonyloxycamptothecin) were determined by HPLC. The unchanged parent drug was the predominant species in bile, with approximately 4% of the dose recovered over 180 min as compared with only 1% for the metabolites. Loperamide significantly reduced the biliary excretion of CPT-11 by approximately 50% (2.0 ± 0.9% dose compared with 3.8 ± 1.0% in the control group, P = 0.019) over the same period. In contrast, the biliary excretion of SN-38, SN-38G and APC was not significantly affected by loperamide (P &gt; 0.05). Furthermore, bile flow rate was not affected by loperamide. Loperamide appeared to selectively inhibit the biliary excretion of CPT-11, although the extent to which loperamide altered the disposition of CPT-11 in the clinical setting remains to be determined.