bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of phosphodiesterase 3 in endotoxin-induced acute kidney injury
Authors: Choi Won-Il , Kwon Kun Young , Seo Jeong Wook , Beagle John , Quinn Deborah A , Hales Charles A 
Published: June 2009

AbstractBackgroundAcute kidney injury frequently accompanies sepsis. Endotoxin is known to reduce tissue levels of cAMP and low levels of cAMP have been associated with renal injury. We, therefore, hypothesized that endotoxin induced renal injury by activating phosphodiesterase 3 (PDE3) which metabolizes cAMP and that amrinone an inhibitor of PDE3 would prevent the renal injury.MethodsAnimals were divided into three groups (n = 7/group): 1) Control (0.9% NaCl infusion without LPS); 2) LPS (0.9% NaCl infusion with LPS); 3) Amrinone+LPS (Amrinone infusion with LPS). Either lipopolysaccharide (LPS) or vehicle was injected via the jugular vein and the rats followed for 3 hours. We explored the expression of PDE3 isoenzymes and the concentrations of cAMP in the tissue.ResultsThe PDE3B gene but not PDE3A was upregulated in the kidney of LPS group. Immunohistochemistry also showed that PDE3B was expressed in the distal tubule in the controls and LPS caused PDE3B expression in the proximal as well. However, PDE3A was not expressed in the kidney either in the control or LPS treated groups. Tissue level of cAMP was decreased after LPS and was associated with an increase in blood urea nitrogen, creatinine, ultrastructural proximal tubular changes, and expression of inducible nitric oxide synthase (iNOS) in the endotoxemic kidney. In septic animals the phosphodiesterase 3 inhibitor, amrinone, preserved the tissue cAMP level, renal structural changes, and attenuated the increased blood urea nitrogen, creatinine, and iNOS expression in the kidney.ConclusionThese findings suggest a significant role for PDE3B as an important mediator of LPS-induced acute kidney injury.
The effect of Lipoxin A4 on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening
Authors: Li Gang , Wu Ping , Xu Yao , Yu Yan , Sun Li , Zhu Liang , Ye Duyun 
Published: June 2009

Abstract

Background
Aseptic loosening (AL) is the main problem of total joints replacement (TJR) by the implantation of permanently prosthetic components. In vitro and in vivo studies have clearly demonstrated that wear debris and its byproducts could trigger inflammation in the peri-implant tissue. Lipoxins (LXs) are endogenous eicosanoids synthesized locally from arachidonate acid (AA) at sites of inflammation and mediate pro-resolving activity. A number of studies have demonstrated the effect of LXA4 to counteract inflammation in different cell and animal models, but till now, no relative report about the role of LXs in progress or prevention of AL.

Methods
Murine RAW264.7 macrophage cell line and MC3T3-E1 osteoblasts (OB) cell line were purchased. Co-cultured model of these two cell lines was established. To explore the effect of exogenous Lipoxin A4 (LXA4) on polymethylmethacrylate (PMMA) induced inflammation, pro-inflammatory cytokines including TNF-α, IL-1β, PGE2 and GM-CSF were measured by ELISA kits and bone resorption was quantified by measuring calcium release from 5-day-old mice calvaria in vitro. To determine further the endogenous effect of LXA4, cells were co-cultured and with or without 15-lipoxygease (15-LO) blocking by 15-LO siRNA. Both real-time PCR and western blotting were applied to confirm the inhibitory efficiency of 15-LO by siRNA.

Results
0.1 mg/ml, 0.5 mg/ml and 1.0 mg/ml PMMA showed a time-dependent manner to trigger production of all the pro-inflammatory cytokines studied. Exogenous 0–100 nM LXA4 presented an inhibitory effect on both generation of above cytokines and PMMA stimulated calvarial bone resorption with a dose-dependent manner. LXA4 in supernatant from neither rest macrophages nor macrophages cultured alone exposing to PMMA was detectable. In co-cultured cells challenged by PMMA, LXA4 was increased significantly, while, this enhance could be partly inhibited by 15-LO siRNA. When LXA4 generation was blocked with 15-LO siRNA, the PMMA induced pro-inflammatory cytokines were elevated and bone resorption was accelerated.

Conclusion
In the present study, we demonstrated that LXA4 had a favorable inhibitory effect on PMMA-induced inflammation in a macrophage and OB co-culture system.
Comparative study on the effect of human BST-2/Tetherin on HIV-1 release in cells of various species
Authors: Sato Kei , Yamamoto Seiji P , Misawa Naoko , Yoshida Takeshi , Miyazawa Takayuki , Koyanagi Yoshio 
Published: June 2009

Abstract
In this study, we first demonstrate that endogenous hBST-2 is predominantly expressed on the plasma membrane of a human T cell line, MT-4 cells, and that Vpu-deficient HIV-1 was less efficiently released than wild-type HIV-1 from MT-4 cells. In addition, surface hBST-2 was rapidly down-regulated in wild-type but not Vpu-deficient HIV-1-infected cells. This is a direct insight showing that provirus-encoded Vpu has the potential to down-regulate endogenous hBST-2 from the surface of HIV-1-infected T cells. Corresponding to previous reports, the aforementioned findings suggested that hBST-2 has the potential to suppress the release of Vpu-deficient HIV-1. However, the molecular mechanism(s) for tethering HIV-1 particles by hBST-2 remains unclear, and we speculated about the requirement for cellular co-factor(s) to trigger or assist its tethering ability. To explore this possibility, we utilize several cell lines derived from various species including human, AGM, dog, cat, rabbit, pig, mink, potoroo, and quail. We found that ectopic hBST-2 was efficiently expressed on the surface of all analyzed cells, and its expression suppressed the release of viral particles in a dose-dependent manner. These findings suggest that hBST-2 can tether HIV-1 particles without the need of additional co-factor(s) that may be expressed exclusively in primates, and thus, hBST-2 can also exert its function in many cells derived from a broad range of species. Interestingly, the suppressive effect of hBST-2 on HIV-1 release in Vero cells was much less pronounced than in the other examined cells despite the augmented surface expression of ectopic hBST-2 on Vero cells. Taken together, our findings suggest the existence of certain cell types in which hBST-2 cannot efficiently exert its inhibitory effect on virus release. The cell type-specific effect of hBST-2 may be critical to elucidate the mechanism of BST-2-dependent suppression of virus release.
Use of nicotine substitute prescribed at hourly plus ad libitum intake or ad libitum for heavy smokers willing to quit: a randomized controlled trial
Authors: Rey Laurent , Vaucher Paul , Secretan Françoise , Zellweger Jean-Pierre , Bodenmann Patrick 
Published: June 2009

Abstract

Objective
To assess the impact of instructional guidance in the regular use of use nicotine nasal spray (NNS) on the true use of NNS during the first three weeks of smoking cessation for heavy smokers who are willing to quit.

Methods
This randomized, open, controlled trial included 50 patients who were heavy smokers, were willing to quit, and attending an academic outpatient clinic in Western Switzerland. Patients were randomised to instruction on NNS use as "ad libitum" (administration whenever cravings appear; control group) or to use NNS when craving appears and at least every hour when awake (intervention group). Intakes were monitored using an electronic device fixed in the spray unit (MDILog™) during the first three weeks of use. Self reported abstinence from smoking at six months was confirmed by expired-air carbon monoxide. Using intention-to-treat analysis, random-effect GLS regression was used to calculate the mean difference of daily doses between groups controlling for lack of independence between measures from the same individual.

Results
One patient was lost to follow-up. At baseline randomization, the group receiving instruction to use NNS hourly included more women, patients with previous desires to quit, and patients with more psychiatric comorbidities and less somatic complaints compared to the group instructed to use NNS with cravings (group imbalance). Both groups self-administered more than the daily recommended dosage of 8 uses. Mean daily usage was 13.6 dose/day and 11.1 dose/day for the group instructed to use NNS hourly and with cravings, respectively. Adjusting for baseline imbalance, the increased daily doses in the intervention group (hourly use) remained nonsignificant compared to ad libitum use (-0.5 dose/day; CI 95% -6.2; 5.3, from day 1 to day 7; and 2.3 dose/day; CI 95% -5.4; 10.0, from day 8 to day 21). Instructing patients to use the NNS daily had no effect on smoking cessation at six months (RR = 0.69; CI 95% 0.34; 1.39).

Conclusion
Heavy smokers willing to quit use NNS frequently, regardless of the instructions given. Recommending the use of NNS only when craving appears for heavy smokers willing to quit seems acceptable compared to prescribing hourly administration.

Trial registration-
ClinicalTrials.gov: NCT00861276
Communities of gastrointestinal helminths of fish in historically connected habitats: habitat fragmentation effect in a carnivorous catfish Pelteobagrus fulvidraco from seven lakes in flood plain of the Yangtze River, China
Authors: Li Wen X , Nie Pin , Wang Gui T , Yao Wei J 
Published: June 2009

AbstractBackgroundHabitat fragmentation may result in the reduction of diversity of parasite communities by affecting population size and dispersal pattern of species. In the flood plain of the Yangtze River in China, many lakes, which were once connected with the river, have become isolated since the 1950s from the river by the construction of dams and sluices, with many larger lakes subdivided into smaller ones by road embankments. These artificial barriers have inevitably obstructed the migration of fish between the river and lakes and also among lakes. In this study, the gastrointestinal helminth communities were investigated in a carnivorous fish, the yellowhead catfishPelteobagrus fulvidraco, from two connected and five isolated lakes in the flood plain in order to detect the effect of lake fragmentation on the parasite communities.ResultsA total of 11 species of helminths were recorded in the stomach and intestine ofP. fulvidracofrom seven lakes, including two lakes connected with the Yangtze River, i.e. Poyang and Dongting lakes, and five isolated lakes, i.e. Honghu, Liangzi, Tangxun, Niushan and Baoan lakes. Mean helminth individuals and diversity of helminth communities in Honghu and Dongting lakes was lower than in the other five lakes. The nematodeProcamallanus fulvidraconiswas the dominant species of communities in all the seven lakes. No significant difference in the Shannon-Wiener index was detected between connected lakes (0.48) and isolated lakes (0.50). The similarity of helminth communities between Niushan and Baoan lakes was the highest (0.6708), and the lowest was between Tangxun and Dongting lakes (0.1807). The similarity was low between Dongting and the other lakes, and the similarity decreased with the geographic distance among these lakes. The helminth community in one connected lake, Poyang Lake was clustered with isolated lakes, but the community in Dongting Lake was separated in the tree.ConclusionThe similarity in the helminth communities of this fish in the flood-plain lakes may be attributed to the historical connection of these habitats and to the completion of the life-cycles of this fish as well as the helminth species within the investigated habitats. The diversity and the digenean majority in the helminth communities can be related to the diet of this fish, and to the lacustrine and macrophytic characters of the habitats. The lake isolation from the river had little detectable effect on the helminth communities of the catfish in flood-plain lakes of the Yangtze River. The low similarities in helminth communities between the Dongting Lake and others may just be a reflection of its unique water environment and anthropogenic alterations or fragmentation in this lake.
Tandem and cryptic amino acid repeats accumulate in disordered regions of proteins
Authors: Simon Michelle , Hancock John M 
Published: June 2009

Abstract
Background
Amino acid repeats (AARs) are common features of protein sequences. They often evolve rapidly and are involved in a number of human diseases. They also show significant associations with particular Gene Ontology (GO) functional categories, particularly transcription, suggesting they play some role in protein function. It has been suggested recently that AARs play a significant role in the evolution of intrinsically unstructured regions (IURs) of proteins. We investigate the relationship between AAR frequency and evolution and their localization within proteins based on a set of 5,815 orthologous proteins from four mammalian (human, chimpanzee, mouse and rat) and a bird (chicken) genome. We consider two classes of AAR (tandem repeats and cryptic repeats: regions of proteins containing overrepresentations of short amino acid repeats).

Results
Mammals show very similar repeat frequencies but chicken shows lower frequencies of many of the cryptic repeats common in mammals. Regions flanking tandem AARs evolve more rapidly than the rest of the protein containing the repeat and this phenomenon is more pronounced for non-conserved repeats than for conserved ones. GO associations are similar to those previously described for the mammals, but chicken cryptic repeats show fewer significant associations. Comparing the overlaps of AARs with IURs and protein domains showed that up to 96% of some AAR types are associated preferentially with IURs. However, no more than 15% of IURs contained an AAR.

Conclusions
Their location within IURs explains many of the evolutionary properties of AARs. Further study is needed on the types of IURs containing AARs.
IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines
Authors: Ortega Consuelo , Fernández-A Silvia , Carrillo Juan M , Romero Pilar , Molina Ignacio J , Moreno José C , Santamaría Manuel 
Published: June 2009

Abstract
Lytic CD8+ T cells at the psoriasis plaque’s epidermis secrete IL-17, IL-21 and IL-22 and depends on autocrine TNFalpha production.
IL-17-producing CD4+ T lymphocytes (Th17) are currently considered relevant participants in the pathogenesis of psoriasis skin lesions. However, little is known about the potential role of IL-17-producing CD8+ T cells, which are also present at the psoriatic plaque. We have addressed the functional characterization of this CD8+ subtype of T lymphocytes from psoriasis patients. Our results show that CD8+IL-17+ cells from psoriasis-inflamed skin tissue produce TNF-α and IFN-γ (Th1-related cytokines) as well as IL-17, IL-21, and IL-22 (Th17-related cytokines) efficiently. A significant up-regulation of the RORC transcription factor is also observed. These cells are refractory to Tregs but show a proliferative response to anti-CD3/CD28 stimulation that is enhanced by IL-12 and IL-15. Blocking of TNF-α activity inhibits TCR-mediated activation and IL-17 production. CD8+IL-17+ T cells are cytotoxic cells that display TCR/CD3-mediated cytotoxic abilities to kill target cells. Thus, CD8+IL-17+ T cells share some key features with Th17 cells and exhibit remarkable differential abilities attributable to the CD8+ lineage of T lymphocytes, adding new insights into the functional resources of IL-17-producing cells from human epidermis that could be of potential interest to our understanding of the pathogenesis of psoriasis.
Expression of ER-α36, a Novel Variant of Estrogen Receptor α, and Resistance to Tamoxifen Treatment in Breast Cancer
Authors: Shi Liang , Dong Bin , Li Zhongwu , Lu Yunwei , Ouyang Tao , Li Jinfeng , Wang Tianfeng , Fan Zhaoqing , Fan Tie , Lin Benyao , Wang Zhaoyi , Xie Yuntao 
Published: June 2009

PurposeRecently, a 36-kDa variant of estrogen receptor α (ER-α66), ER-α36, has been identified and cloned. ER-α36 predominantly localizes on the plasma membrane and in the cytoplasm and mediates a membrane-initiated “nongenomic” signaling pathway. Here, we investigate the association between ER-α36 expression and tamoxifen resistance in patients with breast cancer.Patients and MethodsER-α36 protein expression in tumors from 896 women (two independent cohorts, 1 and 2) with operable primary breast cancer was assessed using an immunohistochemistry assay.ResultsIn the first cohort of 710 consecutive patients, overexpression of ER-α36 was associated with poorer disease-free survival (DFS) and disease-specific survival (DSS) in patients with ER-α66–positive tumors who received tamoxifen treatment (chemotherapy plus tamoxifen or tamoxifen alone, n = 307). In contrast, ER-α36 was not associated with survival in patients with ER-α66–positive tumors who did not receive tamoxifen (chemotherapy alone, n = 129) and in patients with ER-α66–negative tumors whether they received tamoxifen (n = 73) or not (n = 149). In the second cohort of 186 patients who only received tamoxifen as adjuvant therapy, overexpression of ER-α36 was significantly associated with poorer DFS and DSS in 156 ER-α66–positive patients from this cohort, and ER-α36 remained an independent unfavorable factor for both DFS and DSS in these 156 patients by a multivariate analysis (DFS: hazard ratio [HR] = 5.47; 95% CI, 1.81 to 16.51; P =. 003; DSS: HR = 13.97; 95% CI, 1.58 to 123.53; P = .018).ConclusionWomen with ER-α66–positive tumors that also express high levels of ER-α36 are less likely to benefit from tamoxifen treatment.
Significance of Increasing Levels of Minimal Residual Disease in Patients With Philadelphia Chromosome–Positive Chronic Myelogenous Leukemia in Complete Cytogenetic Response
Authors: Kantarjian Hagop M. , Shan Jianqin , Jones Daniel , O'Brien Susan , Rios Mary Beth , Jabbour Elias , Cortes Jorge 
Published: June 2009

Purpose The aim of this study was to evaluate the clinical relevance of increases in quantitative polymerase chain reaction (QPCR) levels in patients with chronic myelogenous leukemia (CML) who are in complete cytogenetic response (CGCR) on therapy. Patients with Philadelphia chromosome (Ph)–positive CML receiving tyrosine kinase inhibitors (TKIs) are frequently monitored for response by QPCR studies for minimal molecular disease. The clinical significance of increasing levels of QPCR in patients in CGCR is uncertain. Patients and Methods One hundred sixteen patients in durable CGCR, and on imatinib therapy for at least 18 months, had increases in QPCR levels (documented at least twice consecutively) as defined by literature reports. These were further analyzed by the achievement of major molecular response (MMR) defined as QPCR ≤ 0.05%, as well as by the degree of increase in QPCR. Results Only 11 (9.5%) of 116 patients with increases in QPCR had CML progression; 10 of them were among 44 patients (23%) who either lost a MMR or never had a MMR, and had more than 1 log increase of QPCR. Conclusion Most patients with increases in QPCR remain in CGCR. Patients who lose a MMR or never achieve a MMR, and have more than 1 log increase of QPCR, should be monitored more closely, and may be evaluated for mutations of BCR-ABL kinase domain and considered for investigational therapeutic interventions.
Outcome of Primary Tumor in Patients With Synchronous Stage IV Colorectal Cancer Receiving Combination Chemotherapy Without Surgery As Initial Treatment
Authors: Poultsides George A. , Servais Elliot L. , Saltz Leonard B. , Patil Sujata , Kemeny Nancy E. , Guillem Jose G. , Weiser Martin , Temple Larissa K.F. , Wong W. Douglas , Paty Phillip B. 
Published: June 2009

Purpose The purpose of this study was to describe the frequency of interventions necessary to palliate the intact primary tumor in patients who present with synchronous, stage IV colorectal cancer (CRC) and who receive up-front modern combination chemotherapy without prophylactic surgery. Patients and Methods By using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin; bolus fluorouracil, leucovorin, and irinotecan; or fluorouracil, leucovorin, and irinotecan) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded. Results Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (ie, stent or radiotherapy), and 213 (89%) never required any direct symptomatic management for their intact primary tumor. Of those 213 patients, 47 patients (20%) ultimately underwent elective colon resection at the time of metastasectomy, and eight patients (3%) underwent this resection during laparotomy for hepatic artery infusion pump placement. Use of bevacizumab, location of the primary tumor in the rectum, and metastatic disease burden were not associated with increased intervention rate. Conclusion Most patients with synchronous, stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary tumor. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease.
Evaluation of the Randox colorimetric serum copper and zinc assays against atomic absorption spectroscopy
Authors: Beckett Jeffrey M , Hartley Thomas F , Ball Madeleine J 
Published: June 2009

Background Analysis of copper and zinc in serum is commonly performed using atomic absorption spectrometry (AAS); however, these methods are often not readily available in smaller laboratories. Randox colorimetric assays for copper and zinc in serum were evaluated on the Thermo Electron Data Pro analyser against flame AAS methods. Methods Copper and zinc were measured in 48 serum samples using the Randox colorimetric copper (CU2340) and zinc (ZN2341) assays on the Data Pro analyser and the results compared with those from a Varian Spectra 880 atomic absorption spectrometer. A smaller set of samples ( n = 15) were also analysed colorimetrically for zinc on the Roche Cobas Mira. Results Linear regression analyses of Bland and Altman plots from the Data Pro – AAS comparison gave the following results for copper: correlation r = 0.6669 ( P < 0.01), slope = −0.2499 ( P < 0.01), intercept = 3.219 ( P < 0.01). For zinc, results were as follows: correlation r = 0.1976, slope = 0.1807, intercept = −1.922. For the smaller set of samples, the Cobas Mira – AAS comparison for zinc gave correlation r = 0.4379, slope = 0.5294, intercept = −4.074. The results indicated significant systematic and fixed bias between the colorimetric copper and the AAS method. Conclusion Performances in comparison to AAS methods indicated the colorimetric methods, as used, are unsuitable for the accurate determination of copper and zinc in human serum.