bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of Androgen and Estrogen Receptor Activity in Prostate Cancer by a Novel Dietary Diterpene Carnosol: Implications for Chemoprevention
Authors: Johnson Jeremy J. , Syed Deeba N. , Suh Yewseok , Heren Chenelle R. , Saleem Mohammad , Siddiqui Imtiaz A. , Mukhtar Hasan 
Published: August 2010

AbstractEmerging data are suggesting that estrogens, in addition to androgens, may also be contributing to the development of prostate cancer (PCa). In view of this notion, agents that target estrogens, in addition to androgens, may be a novel approach for PCa chemoprevention and treatment. Thus, the identification and development of nontoxic dietary agents capable of disrupting androgen receptor (AR) in addition to estrogen receptor (ER) could be extremely useful in the management of PCa. Through molecular modeling, we found that carnosol, a dietary diterpene, fits within the ligand-binding domain of both AR and ER-α. Using a time-resolved fluorescence resonance energy transfer assay, we found that carnosol interacts with both AR and ER-α and additional experiments confirmed that it functions as a receptor antagonist with no agonist effects. LNCaP, 22Rv1, and MCF7 cells treated with carnosol (20-40 μmol/L) showed decreased protein expression of AR and ER-α. Oral administration of carnosol at 30 mg/kg 5 days weekly for 28 days to 22Rv1 PCa xenografted mice suppressed tumor growth by 36% (P = 0.028) and was associated with a decrease in serum prostate-specific antigen by 26% (P = 0.0042). These properties make carnosol unique to any known antiandrogen or antiestrogen investigated thus far for the simultaneous disruption of AR and ER-α. We suggest that carnosol may be developed or chemically modified through more rigorous structure-activity relationship studies for a new class of investigational agents—a dual AR/ER modulator. Cancer Prev Res; 3(9); 1112–23. ©2010 AACR.
Coronary Artery Bypass Grafting After Recent or Remote Percutaneous Coronary Intervention in the Commonwealth of Massachusetts
Authors: Stevens Louis-Mathieu , Khairy Paul , Agnihotri Arvind K. 
Published: August 2010

Background—
In this study, we sought to characterize the outcomes after isolated coronary artery bypass grafting (CABG) in patients with a history of remote (≥14 days), and recent (<14 days), percutaneous coronary intervention (PCI).

Methods and Results—

Patients with PCI within 5 years of CABG were identified among 12 591 primary isolated CABG reported in the mandatory Massachusetts Adult Cardiac Surgery Database. Patients were excluded if they were out-of-state (n=1043, 8%), had undergone primary PCI for acute myocardial infarction (n=401, 3%), had a PCI-CABG interval >5 years or unknown (n=136 and n=673, 1% and 5%). Patients with a history of remote and recent PCI were analyzed separately. Each CABG patient with PCI was matched to 3 patients without PCI using a propensity score. Outcomes were analyzed using generalized estimating equations and stratified proportional hazards models, with a mean follow-up of 4.1±1.2 years. There were 1117 CABG patients (9%) with prior PCI (n
remote
=823; n
recent
=294). In matched CABG patients with remote prior PCI, no differences were found in 30-day mortality (1.1% versus 1.5%;
P
=0.432), hospital morbidity (41% versus 40%;
P
=0.385) and overall survival (hazard ratio, [95% confidence interval] for death for prior PCI, 0.93 [0.74 to 1.18];
P
=0.555). In matched CABG patients with recent prior PCI, hospital morbidity was higher (59% versus 45%;
P
<0.001), but no differences were found in 30-day mortality (3.5% versus 3.1%;
P
=0.754) and overall survival (HR, 1.18 [0.83 to 1.69];
P
=0.353).

Conclusions—
In patients undergoing CABG, remote prior PCI (≥14 days) was not associated with adverse outcomes at 30 days or during long-term follow-up.
The Effect of Age on the Outcomes of Arthroscopic Repair of Type II Superior Labral Anterior and Posterior Lesions
Authors: Alpert Joshua M. , Wuerz Thomas H. , O'Donnell Thomas F. X. , Carroll Kaitlin M. , Brucker Nathan N. , Gill Thomas J. 
Published: August 2010

Background The majority of clinical outcome studies of type II superior labral anterior and posterior (SLAP) repair assess patients younger than age 40. Biceps tenotomy or tenodesis is often recommended for patients older than age 40 with superior labrum-biceps complex injury. Hypothesis There is no difference in patient clinical outcomes comparing arthroscopic type II SLAP repair in patients younger or older than age 40. Study Design Cohort study; Level of evidence, 3. Methods Fifty-two patients stratified to groups younger than age 40 (21 patients; average age, 32.9 years) and older than age 40 (31 patients; average age, 55.1 years) were identified at a minimum 2-year follow-up (average, 28 months) after type II SLAP repair by a single surgeon using suture anchors. Outcome scores included American Shoulder and Elbow Society scores (ASES), Short Form-12 scores, Simple Shoulder Test scores, and visual analog pain scale. Results At follow-up, there was no statistical difference in visual analog pain scale (P = .16), ASES scores (P = .07), Simple Shoulder Test scores (P =.41), Short Form-12 testing, or range of motion testing. Patients older than age 40 noted their shoulder to be 87% of normal; 26 of 31 (84%) were satisfied to completely satisfied, and 28 of 31 (90%) would have the surgery again. Patients younger than 40 noted their shoulder to be approximately 89% of normal; 20 of 21 (95%) were satisfied to completely satisfied, and 18 of 21 (86%) would have the same procedure performed again. Conclusion Our findings support that arthroscopic treatment of isolated type II SLAP repair using suture anchors can yield good to excellent results in patients older and younger than age 40. We found no statistically significant difference in patient outcome scores, satisfaction levels, or willingness to have the same procedure again when comparing arthroscopic SLAP repair in patients younger or older than age 40.
The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo
Authors: Weston Victoria J. , Oldreive Ceri E. , Skowronska Anna , Oscier David G. , Pratt Guy , Dyer Martin J. S. , Smith Graeme , Powell Judy E. , Rudzki Zbigniew , Kearns Pamela , Moss Paul A. H. , Taylor A. Malcolm R. , Stankovic Tatjana 
Published: August 2010

Abstract
The Ataxia Telangiectasia Mutated (ATM) gene is frequently inactivated in lymphoid malignancies such as chronic lymphocytic leukemia (CLL), T-prolymphocytic leukemia (T-PLL), and mantle cell lymphoma (MCL) and is associated with defective apoptosis in response to alkylating agents and purine analogues. ATM mutant cells exhibit impaired DNA double strand break repair. Poly (ADP-ribose) polymerase (PARP) inhibition that imposes the requirement for DNA double strand break repair should selectively sensitize ATM-deficient tumor cells to killing. We investigated in vitro sensitivity to the poly (ADP-ribose) polymerase inhibitor olaparib (AZD2281) of 5 ATM mutant lymphoblastoid cell lines (LCL), an ATM mutant MCL cell line, an ATM knockdown PGA CLL cell line, and 9 ATM-deficient primary CLLs induced to cycle and observed differential killing compared with ATM wildtype counterparts. Pharmacologic inhibition of ATM and ATM knockdown confirmed the effect was ATM-dependent and mediated through mitotic catastrophe independently of apoptosis. A nonobese diabetic/severe combined immunodeficient (NOD/SCID) murine xenograft model of an ATM mutant MCL cell line demonstrated significantly reduced tumor load and an increased survival of animals after olaparib treatment in vivo. Addition of olaparib sensitized ATM null tumor cells to DNA-damaging agents. We suggest that olaparib would be an appropriate agent for treating refractory ATM mutant lymphoid tumors.
The type IV pilin, PilA, is required for full virulence of Francisella tularensis subspecies tularensis
Authors: Forslund Anna-Lena , Salomonsson Emelie Näslund , Golovliov Igor , Kuoppa Kerstin , Michell Stephen , Titball Richard , Oyston Petra , Noppa Laila , Sjöstedt Anders , Forsberg Åke 
Published: August 2010

Abstract

Background
All four Francisella tularensis subspecies possess gene clusters with potential to express type IV pili (Tfp). These clusters include putative pilin genes, as well as pilB, pilC and pilQ, required for secretion and assembly of Tfp. A hallmark of Tfp is the ability to retract the pilus upon surface contact, a property mediated by the ATPase PilT. Interestingly, out of the two major human pathogenic subspecies only the highly virulent type A strains have a functional pilT gene.

Results
In a previous study, we were able to show that one pilin gene, pilA, was essential for virulence of a type B strain in a mouse infection model. In this work we have examined the role of several Tfp genes in the virulence of the pathogenic type A strain SCHU S4. pilA, pilC, pilQ, and pilT were mutated by in-frame deletion mutagenesis. Interestingly, when mice were infected with a mixture of each mutant strain and the wild-type strain, the pilA, pilC and pilQ mutants were out-competed, while the pilT mutant was equally competitive as the wild-type.

Conclusions
This suggests that expression and surface localisation of PilA contribute to virulence in the highly virulent type A strain, while PilT was dispensable for virulence in the mouse infection model.
Transpositional reactivation of the Dart transposon family in rice lines derived from introgressive hybridization with Zizania latifolia
Authors: Wang Ningning , Wang Hongyan , Wang Hui , Zhang Di , Wu Ying , Ou Xiufang , Liu Shuang , Dong Zhenying , Liu Bao 
Published: August 2010

Abstract

Background
It is widely recognized that interspecific hybridization may induce "genome shock", and lead to genetic and epigenetic instabilities in the resultant hybrids and/or backcrossed introgressants. A prominent component involved in the genome shock is reactivation of cryptic transposable elements (TEs) in the hybrid genome, which is often associated with alteration in the elements' epigenetic modifications like cytosine DNA methylation. We have previously reported that introgressants derived from hybridization between Oryza sativa (rice) and Zizania latifolia manifested substantial methylation re-patterning and rampant mobilization of two TEs, a copia retrotransposon Tos17 and a MITE mPing. It was not known however whether other types of TEs had also been transpositionally reactivated in these introgressants, their relevance to alteration in cytosine methylation, and their impact on expression of adjacent cellular genes.

Results
We document in this study that the Dart TE family was transpositionally reactivated followed by stabilization in all three studied introgressants (RZ1, RZ2 and RZ35) derived from introgressive hybridization between rice (cv. Matsumae) and Z. latifolia, while the TEs remained quiescent in the recipient rice genome. Transposon-display (TD) and sequencing verified the element's mobility and mapped the excisions and re-insertions to the rice chromosomes. Methylation-sensitive Southern blotting showed that the Dart TEs were heavily methylated along their entire length, and moderate alteration in cytosine methylation patterns occurred in the introgressants relative to their rice parental line. Real-time qRT-PCR quantification on the relative transcript abundance of six single-copy genes flanking the newly excised or inserted Dart-related TE copies indicated that whereas marked difference in the expression of all four genes in both tissues (leaf and root) were detected between the introgressants and their rice parental line under both normal and various stress conditions, the difference showed little association with the presence or absence of the newly mobilized Dart-related TEs.

Conclusion
Introgressive hybridization has induced transpositional reactivation of the otherwise immobile Dart-related TEs in the parental rice line (cv. Matsumae), which was accompanied with a moderate alteration in the element's cytosine methylation. Significant difference in expression of the Dart-adjacent genes occurred between the introgressants and their rice parental line under both normal and various abiotic stress conditions, but the alteration in gene expression was not coupled with the TEs.
Molecular epidemiology of Hepatitis C virus genotypes in Khyber Pakhtoonkhaw of Pakistan
Authors: Ali Amjad , Ahmed Habib , Idrees Muhammad 
Published: August 2010

Abstract
Six major Hepatitis C virus (HCV) genotypes and hundreds of subtypes have been identified globally. All these genotypes are generally studied for epidemiology, their vaccine development and clinical management. This article comments the frequency distribution of various HCV genotypes circulate in different areas/districts of Khyber Pakhtoonkhaw Province of Pakistan. Sum of 415 HCV RNA PCR positive sera samples were tested by a molecular genotyping assay. Data analysis revealed that out of these 415 HCV RNA positive patients 243 were males and 172 were females. Distribution breakup of the patients was 135, 58, 51, 51, 36, 32, 6, 7and 9 patients come from the districts of Abbottabad, Mardan, Pehawar, Swat, Haripure, Swabi and Dera Ismail Khan, respectively. Out of the tested samples, genotype specific PCR fragments were observed in 299 (74.82%) patient serum samples. The distribution of genotypes of the typeable samples was as fallows: 3 patients (0.72%) each were infected with genotype 1a and genotype 1b; 240 patients (80.26%) of genotype 3a; 25 patients (6.00%) genotype 3b; and 28 patients (6.73%) were observed as with mixed genotypic infection. Sums of 116 serum samples (27.88%) were still found untypeable by the used molecular genotyping system.
In conclusion, HCV genotypes 1a, 1b, 3a and 3b are distributed in various parts of KPK among which the genotype 3a is the most frequent genotype.
Ultrasensitive Responses and Specificity in Cell Signaling
Authors: Haney Seth , Bardwell Lee , Nie Qing 
Published: August 2010

AbstractBackgroundInterconnected cell signaling pathways are able to efficiently and accurately transmit a multitude of different signals, despite an inherent potential for undesirable levels of cross-talk. To ensure that an appropriate response is produced, biological systems have evolved network-level mechanisms that insulate pathways from crosstalk and prevent 'leaking' or 'spillover' between pathways. Many signaling pathways have been shown to respond in an ultrasensitive (switch-like) fashion to graded input, and this behavior may influence specificity. The relationship of ultrasensitivity to signaling specificity has not been extensively explored.ResultsWe studied the behavior of simple mathematical models of signaling networks composed of two interconnected pathways that share an intermediate component, asking if the two pathways in the network could exhibit bothoutput specificity(preferentially activate their own output) andinput fidelity(preferentially respond to their own input). Previous results with weakly-activated pathways indicated that neither mutual specificity nor mutual fidelity were obtainable in the absence of an insulating mechanism, such as cross-pathway inhibition, combinatorial signaling or scaffolding/compartmentalization. Here we found that mutual specificity is obtainable for hyperbolic or ultrasensitive pathways, even in the absence of an insulating mechanism. However, mutual fidelity is impossible at steady-state, even if pathways are hyperbolic or ultrasensitive. Nevertheless, ultrasensitivity does provide advantages in attaining specificity and fidelity to networks that contain an insulating mechanism. For networks featuring cross-pathway inhibition or combinatorial signaling, ultrasensitive activation can increase specificity in a limited way, and can only be utilized by one of the two pathways. In contrast, for networks featuring scaffolding/compartmentalization, ultrasensitive activation of both pathways can dramatically improve network specificity.ConclusionsThere are constraints to obtaining performance objectives associated with signaling specificity; such constraints may have influenced the evolution of signal transduction networks. Notably, input fidelity (preferential response to an authentic input) is a more difficult objective to achieve than output specificity (preferential targeting to an authentic output). Indeed, mutual fidelity is impossible in the absence of an insulating mechanism, even if pathways are ultrasensitive. Ultrasensitivity does, however, significantly enhance the performance of several insulating mechanisms. In particular, the ultrasensitive activation of both pathways can provide substantial improvement to networks containing scaffolding/compartmentalization.
Basic Mechanisms of Arsenic Trioxide (ATO)-Induced Apoptosis in Human Leukemia (HL-60) Cells
Authors: Yedjou Clement , Tchounwou Paul , Jenkins John , McMurray Robert 
Published: August 2010

Abstract

Background
Acute promyelocytic leukemia (APL) is a blood cancer that affects people of all ages and strikes about 1,500 patients in the United States each year. The standard treatment of APL has been based on the combined administration of all-trans retinoic acid and chemotherapy including anthracyclins and cytarabine. However, 10-20% of patients relapse, with their disease becoming resistant to conventional treatment. Recently the Food and Drug Administration has approved the use of arsenic trioxide (ATO) or Trisenox for the treatment of APL, based on clinical studies showing a complete remission, especially in relapsed patients. In a recently published study we demonstrated that ATO pharmacology as an anti-cancer drug is associated with its cytotoxic and genotoxic effects in human leukemia cells.

Methods
In the present study, we further investigated the apoptotic mechanisms of ATO toxicity using the HL-60 cell line as a test model. Apoptosis was measured by flow cytometry analysis of phosphatidylserine externalization (Annexin V assay) and caspase 3 activity, and by DNA laddering assay.

Results
Flow cytometry data showed a strong dose-response relationship between ATO exposure and Annexin-V positive HL-60 cells. Similarly, a statistically significant and dose-dependent increase (p < 0.05) was recorded with regard to caspase 3 activity in HL60 cells undergoing late apoptosis. These results were confirmed by data of DNA laddering assay showing a clear evidence of nucleosomal DNA fragmentation in ATO-treated cells.

Conclusion
Taken together, our research demonstrated that ATO represents an apoptosis-inducing agent and its apoptotic mechanisms involve phosphatidylserine externalization, caspase 3 activation and nucleosomal DNA fragmentation.
Monocytes/macrophages express chemokine receptor CCR9 in rheumatoid arthritis and CCL25 stimulates their differentiation
Authors: Schmutz Caroline , Cartwright Alison , Williams Helen , Haworth Oliver , Williams John HH , Filer Andrew , Salmon Mike , Buckley Christopher D , Middleton Jim 
Published: August 2010

Abstract
Introduction
Monocytes/macrophages accumulate in the rheumatoid (RA) synovium where they play a central role in inflammation and joint destruction. Identification of molecules involved in their accumulation and differentiation is important to inform therapeutic strategies. This study investigated the expression and function of chemokine receptor CCR9 in the peripheral blood (PB) and synovium of RA, non-RA patients and healthy volunteers.

Methods
CCR9 expression on PB monocytes/macrophages was analysed by flow cytometry and in synovium by immunofluorescence. Chemokine receptor CCR9 mRNA expression was examined in RA and non-RA synovium, monocytes/macrophages from PB and synovial fluid (SF) of RA patients and PB of healthy donors using the reverse transcription polymerase chain reaction (RT-PCR). Monocyte differentiation and chemotaxis to chemokine ligand 25 (CCL25)/TECK were used to study CCR9 function.

Results
CCR9 was expressed by PB monocytes/macrophages in RA and healthy donors, and increased in RA. In RA and non-RA synovia, CCR9 co-localised with cluster of differentiation 14+ (CD14+) and cluster of differentiation 68+ (CD68+) macrophages, and was more abundant in RA synovium. CCR9 mRNA was detected in the synovia of all RA patients and in some non-RA controls, and monocytes/macrophages from PB and SF of RA and healthy controls. CCL25 was detected in RA and non-RA synovia where it co-localised with CD14+ and CD68+ cells. Tumour necrosis factor alpha (TNFα) increased CCR9 expression on human acute monocytic leukemia cell line THP-1 monocytic cells. CCL25 induced a stronger monocyte differentiation in RA compared to healthy donors. CCL25 induced significant chemotaxis of PB monocytes but not consistently among individuals.

Conclusions
CCR9 expression by monocytes is increased in RA. CCL25 may be involved in the differentiation of monocytes to macrophages particularly in RA.
Relationship between patient-reported disease severity in osteoarthritis and self-reported pain, function and work productivity
Authors: Sadosky Alesia B , Bushmakin Andrew G , Cappelleri Joseph C , Lionberger David R 
Published: August 2010

Abstract
Introduction
Understanding the relationship between patient-reported osteoarthritis (OA) severity and other patient-reported outcomes in the real-world clinical setting can provide a basis for appropriate patient management. The objective of this study was to determine how patient-reported OA severity correlates with patient-reported outcomes including pain, function and productivity.

Methods
We used the Adelphi Disease Specific Programme (DSP) for OA, a database aggregated from large, multinational, observational studies for specific chronic diseases. Data were obtained based on a 0 to 100 mm pain visual analogue scale (VAS) and a series of questions including functioning (that is, activities of daily living) and work productivity. OA severity was rated by the patients based on the question "How bad would you say your arthritis is now?" with potential responses of "mild," "moderate," and "severe." Regression models and chi-square analyses were used to evaluate the relationships between self-reported OA severity and other outcomes.

Results
Of 998 subjects in the OA DSP U.S. database, 714 (72.5%) agreed to participate. This sample was predominantly female (61.7%) with a mean age of 63.8 ± 12.9 years. Increased OA severity was associated with an older population (P < 0.05). With increasing OA severity (mild, moderate, severe), statistically significant differences (P < 0.05) were observed in increased pain VAS scores (23.5, 50.2, 70.8, respectively), lower functioning outcomes, and a higher percent of overall work impairment due to OA (17%, 37%, 48%, respectively). The increased work impairment at greater severity levels also resulted in higher costs related to lost work productivity, with annual costs due to lost productivity estimated at $6,096, $13,2510, and $17,214 per patient for self-reported mild, moderate, and severe OA, respectively (P < 0.05 for pairwise comparisons).

Conclusions
In the clinical practice setting, patient-reported OA severity was associated with other key patient-reported outcomes and thus may provide an accurate and tangible assessment of patients' perceptions of their disease. Identifying OA patients by their perceived severity level may be of benefit to patients and health-care providers when choosing treatment options aimed at reducing pain, and improving function and productivity.