bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further analysis of previously implicated linkage regions for Alzheimer's disease in affected relative pairs
Authors: Blom Elin S , Giedraitis Vilmantas , Arepalli Sampath , Hamshere Marian L , Adighibe Omanma , Goate Alison , Williams Julie , Lannfelt Lars , Hardy John , Vrièze Fabienne Wavrant-De , Glaser Anna 
Published: December 2009

Abstract

Background
Genome-wide linkage studies for Alzheimer's disease have implicated several chromosomal regions as potential loci for susceptibility genes.

Methods
In the present study, we have combined a selection of affected relative pairs (ARPs) from the UK and the USA included in a previous linkage study by Myers et al. (Am J Med Genet, 2002), with ARPs from Sweden and Washington University. In this total sample collection of 397 ARPs, we have analyzed linkage to chromosomes 1, 9, 10, 12, 19 and 21, implicated in the previous scan.

Results
The analysis revealed that linkage to chromosome 19q13 close to the APOE locus increased considerably as compared to the earlier scan. However, linkage to chromosome 10q21, which provided the strongest linkage in the previous scan could not be detected.

Conclusion
The present investigation provides yet further evidence that 19q13 is the only chromosomal region consistently linked to Alzheimer's disease.
Expression of indoleamine 2,3-dioxygenase in nasopharyngeal carcinoma impairs the cytolytic function of peripheral blood lymphocytes
Authors: Liu Peng , Xie Bai-Lu , Cai Shao-Hui , He Yun-Wen , Zhang Ge , Yi Yan-Mei , Du Jun 
Published: December 2009

Abstract

Background
Tumor-specific cytotoxic T cells and infiltrating lymphocytes are frequently found in tumor tissues in patients with nasopharyngeal carcinoma (NPC). Most patients with NPC, however, especially those with advanced stages, have a poor clinical prognosis despite conventional immunotherapy. The aim of this work was to examine the effect of indoleamine 2,3-dioxygenase (IDO), an immunosuppressive enzyme, on the lymphocyte function in NPC.

Methods
The NPC cell line CNE2 was treated by interferon-γ (IFNγ) and the levels of IDO expression was analyzed by Western blotting and reverse phase high-performance liquid chromatography (HPLC). Lymphocytes from health human exposed to the milieu created by IDO-positive CNE2 cells and the lymphocyte cytotoxicity to target tumor cells was analyzed by standard lactate dehydrogenase (LDH) release assay. Additionally, expression of IDO was determined by Immunohistochemical assay in the tumor tissues form clinically evaluated NPC.

Results
IDO expression was acutely induced in the NPC cell line CNE2 by low dose interferon-γ (IFNγ) or by co-incubation with activated lymphocytes. Exposure to the milieu created by IDO-positive CNE2 cells did not promote lymphocyte death, but lymphocyte cytotoxicity against target tumor cells was impaired. The suppression of lymphocyte cytotoxic function was fully restored when the conditioned medium was replaced by fresh medium for 24 h. In additionally, the IDO-positive cells were found scattered in the tumor tissues from patients with NPC.

Conclusion
Altogether, these findings suggest that IDO-mediated immunosuppression may be involved in the tumor immune evasion, and that blocking IDO activity in tumor cells may help to re-establish an effective anti-tumor T cell response in NPC.
Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes
Authors: Tardif Ginette , Hum David , Pelletier Jean-Pierre , Duval Nicolas , Martel-Pelletier Johanne 
Published: December 2009

Abstract

Background
MMP-13 and IGFBP-5 are important factors involved in osteoarthritis (OA). We investigated whether two highly predicted microRNAs (miRNAs), miR-140 and miR-27a, regulate these two genes in human OA chondrocytes.

Methods
Gene expression was determined by real-time PCR. The effect of each miRNA on IGFBP-5 and MMP-13 expression/production was evaluated by transiently transfecting their precursors (pre-miRNAs) and inhibitors (anti-miRNAs) into human OA chondrocytes. Modulation of IGFBP-5, miR-140 and miR-27a expression was determined upon treatment of OA chondrocytes with cytokines and growth factors.

Results
IGFBP-5 was expressed in human chondrocytes with its level significantly lower (p < 0.04) in OA. Five computational algorithms identified miR-140 and miR-27a as possible regulators of MMP-13 and IGFBP-5 expression. Data showed that both miRNAs were expressed in chondrocytes. There was a significant reduction (77%, p < 0.01) in miR-140 expression in OA compared to the normal chondrocytes, whereas miR-27a expression was only slightly decreased (23%). Transfection with pre-miR-140 significantly decreased (p = 0.0002) and with anti-miR-140 significantly increased (p = 0.05) IGFBP-5 expression at 24 hours, while pre-miR-27a did not affect either MMP-13 or IGFBP-5. Treatment with anti-miR-27a, but not with anti-miR-140, significantly increased the expression of both MMP-13 (p < 0.05) and IGFBP-5 (p < 0.01) after 72 hours of incubation. MMP-13 and IGFBP-5 protein production followed the same pattern as their expression profile. These data suggest that IGFBP-5 is a direct target of miR-140, whereas miR-27a down-regulates, likely indirectly, both MMP-13 and IGFBP-5.

Conclusion
This study is the first to show the regulation of these miRNAs in human OA chondrocytes. Their effect on two genes involved in OA pathophysiology adds another level of complexity to gene regulation, which could open up novel avenues in OA therapeutic strategies.
Oral administration of PPC enhances antigen-specific CD8+ T cell responses while reducing IgE levels in sensitized mice
Authors: Burrows Mike , Assundani Deepak , Celis Esteban , Tufaro Frank , Tanaka Akiko , Bradley W Guy 
Published: December 2009

AbstractBackgroundFor almost 2000 years it has been recognized that aqueous extracts from pine cones possess medicinal properties beneficial for the treatment of a broad variety of diseases and conditions. In this report, the ability of an orally administered poly phenylpropanoid-polysaccharide rich extract of pine cones (PPC) to suppress the generation of IgE and to significantly enhance antigen-specific cellular responses to a variety of vaccines was tested.MethodsA variety of vaccine protocols were utilized to determine the affects of orally administered PPC on the Th1/Th2 cytokine balance, the production of IgE antibodies, and the generation of antigen-specific cytotoxic T cells. The effect of PPC on the Th1/Th2 balance in aged mice was also investigated.ResultsOral delivery of PPC was found to significantly suppress serum IgE levels in naïve mice and in mice sensitized to ovalbumin. PPC was also found to enhance the generation of antigen-specific CD8+T cells in mice immunized with DNA, dendritic cell, and soluble protein vaccines. The suppression of IgE was associated with reduction of IL-4 secretion and the enhanced production of IL-12 and IFNγby antigen-stimulated splenocytes from PPC treated mice. PPC also suppressed the Th2 response and enhanced the Th1 response of splenocytes from aged mice.ConclusionOral delivery of PPC enhances the generation of an antigen-specific CD8+T cell responses induced by soluble protein, DNA, and dendritic cell vaccines while at the same time suppressing the generation of a Th2 dominant IgE response. This effect on the Th1/Th2 balance was also observed in aged mice.
Trends in health services utilization, medication use, and health conditions among older adults: a 2-year retrospective chart review in a primary care practice
Authors: Vegda Ketan , Nie Jason X , Wang Li , Tracy C Shawn , Moineddin Rahim , Upshur Ross EG 
Published: December 2009

Abstract

Background
Population aging poses significant challenges to primary care providers and healthcare policy makers. Primary care reform can alleviate the pressures, but these initiatives require clinical benchmarks and evidence regarding utilization patterns. The objectives of this study is to measure older patients' use of health services, number of health conditions, and use of medications at the level of a primary care practice, and to investigate age- and gender-related utilization trends.

Methods
A cross-sectional chart audit over a 2-year study period was conducted in the academic family practice clinic of Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada. All patients 65 years and older (n = 2450) were included. Main outcome measures included the number of family physician visits, specialist visits, emergency room visits, surgical admissions, diagnostic test days, inpatient hospital admissions, health conditions, and medications.

Results
Older patients (80-84 and 85+ age-group) had significantly more family physician visits (average of 4.4 visits per person per year), emergency room visits (average of 0.22 ER visits per year per patient), diagnostic days (average of 5.1 test days per person per year), health conditions (average of 7.7 per patient), and medications average of 8.2 medications per person). Gender differences were also observed: females had significantly more family physician visits and number of medications, while men had more specialist visits, emergency room visits, and surgical admissions. There were no gender differences for inpatient hospital admissions and number of health conditions. With the exception of the 85+ age group, we found greater intra-group variability with advancing age.

Conclusion
The data present a map of greater interaction with and dependency on the health care system with advancing age. The magnitudes are substantial and indicate high demands on patients and families, on professional health care providers, and on the health care system itself. There is the need to create and evaluate innovative models of care of multiple chronic conditions in the late life course.
Induction of apoptosis in HeLa cells by chloroform fraction of seed extracts of Nigella sativa
Authors: Shafi Gowhar , Munshi Anjana , Hasan Tarique N , Alshatwi Ali A , Jyothy A , Lei David KY 
Published: December 2009

Abstract

Background
Cancer remains one of the most dreaded diseases causing an astonishingly high death rate, second only to cardiac arrest. The fact that conventional and newly emerging treatment procedures like chemotherapy, catalytic therapy, photodynamic therapy and radiotherapy have not succeeded in reverting the outcome of the disease to any drastic extent, has made researchers investigate alternative treatment options. The extensive repertoire of traditional medicinal knowledge systems from various parts of the world are being re-investigated for their healing properties. This study progresses in the direction of identifying component(s) from Nigella sativa with anti cancer acitivity. In the present study we investigated the efficacy of Organic extracts of Nigella sativa seed powder for its clonogenic inhibition and induction of apoptosis in HeLa cancer cell.

Results
Methanolic, n-Hexane and chloroform extracts of Nigella sativa seedz effectively killed HeLa cells. The IC50 values of methanolic, n-hexane, and chloroform extracts of Nigella sativa were 2.28 μg/ml, 2.20 μg/ml and 0.41 ng/ml, respectively. All three extracts induced apoptosis in HeLa cells. Apoptosis was confirmed by DNA fragmentation, western blot and terminal transferase-mediated dUTP-digoxigenin-end labeling (TUNEL) assay.

Conclusion
Western Blot and TUNEL results suggested that Nigella sativa seed extracts regulated the expression of pro- and anti- apoptotic genes, indicating its possible development as a potential therapeutic agent for cervical cancer upon further investigation.
Dual effects of TGF-β on ERα-mediated estrogenic transcriptional activity in breast cancer
Authors: Ren Yongsheng , Wu Liyu , Frost Andra R , Grizzle William , Cao Xu , Wan Mei 
Published: December 2009

AbstractBackgroundTGF-β resistance often develops in breast cancer cells that in turn overproduce this cytokine to create a local immunosuppressive environment that fosters tumor growth and exacerbates the invasive and metastatic behavior of the tumor cells themselves. Smads-mediated cross-talk with the estrogen receptor has been implied to play an important role in development and/or progression of breast cancer. We investigated how TGF-β regulates ERα-induced gene transcription and potential mechanisms of frequent TGF-β resistance in breast cancer.MethodsEffect of TGF-β on ERα-mediated gene transcription was investigated in breast cancer cell lines using transient transfection, real-time PCR, sequential DNA precipitation, and small interfering RNA assays. The expression of Smads on both human breast cancer cell lines and ERα-positive human breast cancer tissue was evaluated by immunofluorescence and immunohistochemical assays.ResultsA complex of Smad3/4 mediates TGF-β inhibition of ERα-mediated estrogenic activity of gene transcription in breast cancer cells, and Smad4 is essential and sufficient for such repression. Either overexpression of Smad3 or inhibition of Smad4 leads to the "switch" of TGF-β from a repressor to an activator. Down-regulation and abnormal cellular distribution of Smad4 were associated with some ERα-positive infiltrating human breast carcinoma. There appears a dynamic change of Smad4 expression from benign breast ductal tissue to infiltrating ductal carcinoma.ConclusionThese results suggest that aberrant expression of Smad4 or disruption of Smad4 activity lead to the loss of TGF-β suppression of ERα transactivity in breast cancer cells.
GLI1 genotypes do not predict basal cell carcinoma risk: a case control study
Authors: Watson Andrea , Kent Paul , Alam Murad , Paller Amy S , Umbach David M , Yoon Joon Won , Iannaccone Philip M , Walterhouse David O 
Published: December 2009

Abstract

Background
Susceptibility to basal cell carcinoma results from complex interactions between ultraviolet radiation exposure and genetic factors. The GLI1 oncogene is believed to play a role in the genesis of these tumors. We determined whether GLI1 polymorphisms were risk factors for developing basal cell carcinoma, either alone or in combination with patterns of past sun exposure, and whether there were functional differences among different GLI1 haplotypes.

Results

GLI1 genotypes at c.2798 and c.3298 from 201 basal cell carcinoma patients were compared to 201 age and sex-matched controls. Neither genotype nor haplotype frequencies differed between cases and controls. However, the odds of developing basal cell carcinoma on the trunk compared to the head/neck appeared somewhat lower with carriers of the c.3298GC than the CC genotype. There was no evidence for interactions between skin type, childhood sunburning, average adult sun exposure, adult sunbathing, or intermittency of sun exposure and GLI1 haplotype. Additionally, we found no significant differences in transcription activation or cell transforming ability among the four GLI1 haplotypes.

Conclusion
These results suggest that different GLI1 genotypes alone or in combination with past sun exposure patterns as assessed in this study do not affect basal cell carcinoma risk.
Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease
Authors: Ronald James , Rajagopalan Ramakrishnan , Ranchalis Jane E , Marshall Julieann K , Hatsukami Thomas S , Heagerty Patrick J , Jarvik Gail P 
Published: December 2009

AbstractBackgroundGenome-wide association studies have identified numerous single nucleotide polymorphisms (SNPs) affecting high density lipoprotein (HDL) or low density lipoprotein (LDL) cholesterol levels; these SNPs may contribute to the genetic basis of vascular diseases.ResultsWe assessed the impact of 34 SNPs at 23 loci on dyslipidemia, key lipid sub-phenotypes, and severe carotid artery disease (CAAD) in a case-control cohort. The effects of these SNPs on HDL and LDL were consistent with those previously reported, and we provide unbiased estimates of the percent variance in HDL (3.9%) and LDL (3.3%) explained by genetic risk scores. We assessed the effects of these SNPs on HDL subfractions, apolipoprotein A-1, LDL buoyancy, apolipoprotein B, and lipoprotein (a) and found that rs646776 predicts apolipoprotein B level while rs2075650 predicts LDL buoyancy. Finally, we tested the role of these SNPs in conferring risk for ultrasonographically documented CAAD stenosis status. We found that two loci, chromosome 1p13.3 near CELSR2 and PSRC1 which contains rs646776, and 19q13.2 near TOMM40 and APOE which contains rs2075650, harbor risk alleles for CAAD.ConclusionOur analysis of 34 SNPs contributing to dyslipidemia at 23 loci suggests that genetic variation in the 1p13.3 region may increase risk of CAAD by increasing LDL particle number, whereas variation in the 19q13.2 region may increase CAAD risk by promoting formation of smaller, denser LDL particles.
Isolation and characterization of a strain of Lichtheimia corymbifera (ex Absidia corymbifera) from a case of bovine abortion
Authors: Piancastelli Chiara , Ghidini Francesca , Donofrio Gaetano , Jottini Stefano , Taddei Simone , Cavirani Sandro , Cabassi Clotilde S 
Published: December 2009

Abstract

Background
Lichtheimia corymbifera (previously Absidia corymbifera) is a filamentous zygomycetes belonging to the order Mucorales and to the family Lichtheimiaceae. Members of genus Lichtheimia spp. are cosmopolitan and ubiquitous in nature. Lichtheimia corymbifera is a recognized agent of diseases in man and animals. In cattle it causes abortion and mastitis. Three cases of bovine abortion occurred in a herd located in the Po Valley. Serological examinations were performed on fetal and mother's blood. One of the aborted fetus was referred to our laboratory. The paper describes the isolation and characterization of Lichtheimia corymbifera from a bovine aborted fetus.

Methods
Serological examinations were performed on fetal and mother's blood. Lesions on fetal tissues and placenta leaded the diagnostic suspect towards a mycotic aetiology. Tissues were then put in culture, and at the same time an histological examination was performed, together with bacteriological and virological tests. The isolate from placenta and fetal tissues was identified and characterized by PCR and RFLP, using the ITS region as a target sequence and AclI restriction site within the amplicon to distinguish Lichtheimia corymbifera among the other fungi.

Results
Serological, bacteriological and virological tests gave aspecific results. Histological examination evidenced numerous PAS positive hyphae within the necrotic cotiledons and numerous fungal nonseptate hyphae to the GMS stain. Colonies with typical morphological features of fungi grew up on Sabouraud agar from fetal skin and placenta. On the developed colonies the microscopic examination has shown a large number of nonseptate hyphae and sporangia consistent with Mucorales. PCR and RFLP allowed the identification of the isolate as Lichtheimia corymbifera.

Conclusion
The present report describes the isolation and the molecular characterisation of a fungal isolate from bovine aborted fetus and placenta. The diagnostic protocol allowed to identify and characterise the strain. This is the first isolation in Italy of Lichtheimia corymbifera in a bovine aborted fetus.
Proteomic analysis of blastema formation in regenerating axolotl limbs
Authors: Rao Nandini , Jhamb Deepali , Milner Derek J , Li Bingbing , Song Fengyu , Wang Mu , Voss S Randal , Palakal Mathew , King Michael W , Saranjami Behnaz , Nye Holly LD , Cameron Jo Ann , Stocum David L 
Published: December 2009

Abstract

Background

Following amputation, urodele salamander limbs reprogram somatic cells to form a blastema that self-organizes into the missing limb parts to restore the structure and function of the limb. To help understand the molecular basis of blastema formation, we used quantitative label-free liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS)-based methods to analyze changes in the proteome that occurred 1, 4 and 7 days post amputation (dpa) through the mid-tibia/fibula of axolotl hind limbs.

Results

We identified 309 unique proteins with significant fold change relative to controls (0 dpa), representing 10 biological process categories: (1) signaling, (2) Ca2+ binding and translocation, (3) transcription, (4) translation, (5) cytoskeleton, (6) extracellular matrix (ECM), (7) metabolism, (8) cell protection, (9) degradation, and (10) cell cycle. In all, 43 proteins exhibited exceptionally high fold changes. Of these, the ecotropic viral integrative factor 5 (EVI5), a cell cycle-related oncoprotein that prevents cells from entering the mitotic phase of the cell cycle prematurely, was of special interest because its fold change was exceptionally high throughout blastema formation.

Conclusion

Our data were consistent with previous studies indicating the importance of inositol triphosphate and Ca2+ signaling in initiating the ECM and cytoskeletal remodeling characteristic of histolysis and cell dedifferentiation. In addition, the data suggested that blastema formation requires several mechanisms to avoid apoptosis, including reduced metabolism, differential regulation of proapoptotic and antiapoptotic proteins, and initiation of an unfolded protein response (UPR). Since there is virtually no mitosis during blastema formation, we propose that high levels of EVI5 function to arrest dedifferentiated cells somewhere in the G1/S/G2 phases of the cell cycle until they have accumulated under the wound epidermis and enter mitosis in response to neural and epidermal factors. Our findings indicate the general value of quantitative proteomic analysis in understanding the regeneration of complex structures.
The use of body weight support on ground level: an alternative strategy for gait training of individuals with stroke
Authors: Sousa Catarina O , Barela José A , Prado-Medeiros Christiane L , Salvini Tania F , Barela Ana MF 
Published: December 2009

Abstract

Background
Body weight support (BWS) systems on treadmill have been proposed as a strategy for gait training of subjects with stroke. Considering that ground level is the most common locomotion surface and that there is little information about individuals with stroke walking with BWS on ground level, it is important to investigate the use of BWS on ground level in these individuals as a possible alternative strategy for gait training.

Methods
Thirteen individuals with chronic stroke (four women and nine men; mean age 54.46 years) were videotaped walking on ground level in three experimental conditions: with no harness, with harness bearing full body weight, and with harness bearing 30% of full body weight. Measurements were recorded for mean walking speed, cadence, stride length, stride speed, durations of initial and terminal double stance, single limb support, swing period, and range of motion of ankle, knee, and hip joints; and foot, shank, thigh, and trunk segments.

Results
The use of BWS system leads to changes in stride length and speed, but not in stance and swing period duration. Only the hip joint was influenced by the BWS system in the 30% BWS condition. Shank and thigh segments presented less range of motion in the 30% BWS condition than in the other conditions, and the trunk was held straighter in the 30% BWS condition than in the other conditions.

Conclusion
Individuals with stroke using BWS system on ground level walked slower and with shorter stride length than with no harness. BWS also led to reduction of hip, shank, and thigh range of motion. However, this system did not change walking temporal organization and body side asymmetry of individuals with stroke. On the other hand, the BWS system enabled individuals with chronic stroke to walk safely and without physical assistance. In interventions, the physical therapist can watch and correct gait pattern in patients' performance without the need to provide physical assistance.