bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal kallikrein excretion and epigenetics in human acute kidney injury: Expression, mechanisms and consequences
Authors: Kang Sun Woo , Shih Pei-an Betty , Mathew Roy O , Mahata Manjula , Biswas Nilima , Rao Fangwen , Yan Liying , Bouchard Josee , Malhotra Rakesh , Tolwani Ashita , Khandrika Srikrishna , Mehta Ravindra L , O'Connor Daniel T 
Published: June 2011

Abstract

Background
Renal kallikrein (KLK1) synthesis and urinary excretion are reportedly diminished during AKI (acute kidney injury) in animal models, and provision of kallikrein abrogates renal injury in this setting, but data in human AKI is limited. Therefore we first examined KLK1 renal excretion in human AKI, and then probed potential endocrine and epigenetic mechanisms for its alterations.

Methods
KLK1 enzymatic activity excretion was evaluated in urine from patients with established or incipient AKI, versus healthy/non-hospital as well as ICU controls. Endocrine control of KLK1 excretion was then probed by catecholamine and aldosterone measurements in established AKI versus healthy controls. To examine epigenetic control of KLK1 synthesis, we tested blood and urine DNA for changes in promoter CpG methylation of the KLK1 gene, as well as LINE-1 elements, by bisulfite sequencing.

Results
Patients with early/incipient AKI displayed a modest reduction of KLK1 excretion, but unexpectedly, established AKI displayed substantially elevated urine KLK1 excretion, ~11-fold higher than healthy controls, and ~3-fold greater than ICU controls. We then probed potential mechanisms of the change. Established AKI patients had lower SBP, higher heart rate, and higher epinephrine excretion than healthy controls, though aldosterone excretion was not different. Promoter KLK1 CpG methylation was higher in blood than urine DNA, while KLK1 methylation in blood DNA was significantly higher in established AKI than healthy controls, though KLK1 methylation in urine tended to be higher in AKI, directionally consistent with earlier/incipient but not later/established changes in KLK1 excretion in AKI. On multivariate ANOVA, AKI displayed coordinate changes in KLK1 excretion and promoter methylation, though directionally opposite to expectation. Control (LINE-1 repetitive element) methylation in blood and urine DNA was similar between AKI and controls.

Conclusions
Unexpectedly, increased KLK1 excretion in AKI patients was found; this increase is likely to be due in part to increments in adrenergic tone during BP depression. Epigenetic changes at KLK1 may also play a role in early changes of KLK1 expression and thus AKI susceptibility or recovery.
Successful twin pregnancy in a patient with parkin-associated autosomal recessive juvenile parkinsonism
Authors: Serikawa Takehiro , Shimohata Takayoshi , Akashi Mami , Yokoseki Akio , Tsuchiya Miwa , Hasegawa Arika , Haino Kazufumi , Koike Ryoko , Takakuwa Koichi , Tanaka Keiko , Tanaka Kenichi , Nishizawa Masatoyo 
Published: June 2011

Abstract

Background
Pregnancy in patients with Parkinson disease is a rare occurrence. To the best of our knowledge, the effect of pregnancy as well as treatment in genetically confirmed autosomal recessive juvenile parkinsonism (ARJP) has never been reported. Here, we report the first case of pregnancy in a patient with ARJP associated with a parkin gene mutation, ARJP/PARK2.

Case presentation
A 27-year-old woman with ARJP/PARK2 was diagnosed as having a spontaneous dichorionic/diamniotic twin pregnancy. Exacerbation of motor disability was noted between ovulation and menstruation before pregnancy as well as during late pregnancy, suggesting that her parkinsonism might have been influenced by fluctuations in the levels of endogenous sex hormones. During the organogenesis period, she was only treated with levodopa/carbidopa, although she continued to receive inpatient hospital care for assistance in the activities of daily living. After the organogenesis period, she was administered sufficient amounts of antiparkinsonian drugs. She delivered healthy male twins, and psychomotor development of both the babies was normal at the age of 2 years.

Conclusion
Pregnancy may worsen the symptoms of ARJP/PARK2, although appropriate treatments with antiparkinsonian drugs and adequate assistance in the activities of daily living might enable successful pregnancy and birth of healthy children.
Therapeutic potential of cladribine in combination with STAT3 inhibitor against multiple myeloma
Authors: Ma Jian , Wang Shuiliang , Zhao Ming , Deng Xin-Sheng , Lee Choon-Kee , Yu Xiao-Dan , Liu Bolin 
Published: June 2011

Abstract

Background
Cladribine or 2-chlorodeoxyadenosine (2-CDA) is a well-known purine nucleoside analog with particular activity against lymphoproliferative disorders, such as hairy cell leukemia (HCL). Its benefits in multiple myeloma (MM) remain unclear. Here we report the inhibitory effects of cladribine on MM cell lines (U266, RPMI8226, MM1.S), and its therapeutic potential in combination with a specific inhibitor of the signal transducer and activator of transcription 3 (STAT3).

Methods
MTS-based proliferation assays were used to determine cell viability in response to cladribine. Cell cycle progression was examined by flow cytometry analysis. Cells undergoing apoptosis were evaluated with Annexin V staining and a specific ELISA to quantitatively measure cytoplasmic histone-associated DNA fragments. Western blot analyses were performed to determine the protein expression levels and activation.

Results
Cladribine inhibited cell proliferation of MM cells in a dose-dependent manner, although the three MM cell lines exhibited a remarkably different responsiveness to cladribine. The IC50 of cladribine for U266, RPMI8226, or MM1.S cells was approximately 2.43, 0.75, or 0.18 μmol/L, respectively. Treatment with cladribine resulted in a significant G1 arrest in U266 and RPMI8226 cells, but only a minor increase in the G1 phase for MM1.S cells. Apoptosis assays with Annexin V-FITC/PI double staining indicated that cladribine induced apoptosis of U266 cells in a dose-dependent manner. Similar results were obtained with an apoptotic-ELISA showing that cladribine dramatically promoted MM1.S and RPMA8226 cells undergoing apoptosis. On the molecular level, cladribine induced PARP cleavage and activation of caspase-8 and caspase-3. Meanwhile, treatment with cladribine led to a remarkable reduction of the phosphorylated STAT3 (P-STAT3), but had little effect on STAT3 protein levels. The combinations of cladribine and a specific STAT3 inhibitor as compared to either agent alone significantly induced apoptosis in all three MM cell lines.

Conclusions
Cladribine exhibited inhibitory effects on MM cells in vitro. MM1.S is the only cell line showing significant response to the clinically achievable concentrations of cladribine-induced apoptosis and inactivation of STAT3. Our data suggest that MM patients with the features of MM1.S cells may particularly benefit from cladribine monotherapy, whereas cladribine in combination with STAT3 inhibitor exerts a broader therapeutic potential against MM.
Rural-urban differences of neonatal mortality in a poorly developed province of China
Authors: Yi Bin , Wu Li , Liu Hong , Fang Weimin , Hu Yang , Wang Youjie 
Published: June 2011

Abstract

Background
The influence of rural-urban disparities in children's health on neonatal death in disadvantaged areas of China is poorly understood. In this study of rural and urban populations in Gansu province, a disadvantaged province of China, we describe the characteristics and mortality of newborn infants and evaluated rural-urban differences of neonatal death.

Methods
We analyzed all neonatal deaths in the data from the Surveillance System of Child Death in Gansu Province, China from 2004 to 2009. We calculated all-cause neonatal mortality rates (NMR) and cause-specific death rates for infants born to rural or urban mothers during 2004-09. Rural-urban classifications were determined based on the residence registry system of China. Chi-square tests were used to compare differences of infant characteristics and cause-specific deaths by rural-urban maternal residence.

Results
Overall, NMR fell in both rural and urban populations during 2004-09. Average NMR for rural and urban populations was 17.8 and 7.5 per 1000 live births, respectively. For both rural and urban newborn infants, the four leading causes of death were birth asphyxia, preterm or low birth weight, congenital malformation, and pneumonia. Each cause-specific death rate was higher in rural infants than in urban infants. More rural than urban neonates died out of hospital or did not receive medical care before death.

Conclusions
Neonatal mortality declined dramatically both in urban and rural groups in Gansu province during 2004-09. However, profound disparities persisted between rural and urban populations. Strategies that address inequalities of accessibility and quality of health care are necessary to improve neonatal health in rural settings in China.
Applying the revised Chinese Job Content Questionnaire to assess psychosocial work conditions among Taiwan's hospital workers
Authors: Chien Tsair-Wei , Lai Wen-Pin , Wang Hsien-Yi , Hsu Sen-Yen , Castillo Roberto Vasquez , Guo How-Ran , Chen Shih-Chung , Su Shih-Bin 
Published: June 2011

Abstract

Background
For hospital accreditation and health promotion reasons, we examined whether the 22-item Job Content Questionnaire (JCQ) could be applied to evaluate job strain of individual hospital employees and to determine the number of factors extracted from JCQ. Additionally, we developed an Excel module of self-evaluation diagnostic system for consultation with experts.

Methods
To develop an Excel-based self-evaluation diagnostic system for consultation to experts to make job strain assessment easier and quicker than ever, Rasch rating scale model was used to analyze data from 1,644 hospital employees who enrolled in 2008 for a job strain survey. We determined whether the 22-item Job Content Questionnaire (JCQ) could evaluate job strain of individual employees in work sites. The respective item responding to specific groups' occupational hazards causing job stress was investigated by using skewness coefficient with its 95% CI through item-by-item analyses.

Results
Each of those 22 items on the questionnaire was examined to have five factors. The prevalence rate of Chinese hospital workers with high job strain was 16.5%.

Conclusions
Graphical representations of four quadrants, item-by-item bar chart plots and skewness 95% CI comparison generated in Excel can help employers and consultants of an organization focusing on a small number of key areas of concern for each worker in job strain.
Hypericum lanceolatum (Hypericaceae) as a potential source of new anti-malarial agents: a bioassay-guided fractionation of the stem bark
Authors: Zofou Denis , Kowa Théodora K , Wabo Hippolyte K , Ngemenya Moses N , Tane Pierre , Titanji Vincent PK 
Published: June 2011

Abstract

Background
Malaria is a major public health threat in Africa, and traditional medicine continues to play a key role in its control especially in rural areas. A bioassay-guided fractionation was carried out in order to evaluate the anti-malarial potential and the safety of the methanol extract of the Hypericum lanceolatum stem bark.

Methods
The anti-plasmodial activity was assayed by the lactate dehydrogenase method (pLDH) against the multidrug-resistant W2mef laboratory strain, and a field isolate (SHF4) of Plasmodium falciparum. Cytotoxicity tests were carried out using the LLC-MK2 monkey kidney epithelial cells.

Results
Five compounds were isolated from the most active and least cytotoxic ethylacetate sub-extract: betulinic acid (HLT1), 2,2',5,6'-tetrahydroxybenzophenone (HLT2), 5-hydroxy-3-methoxyxanthone (HLT3), 3-hydroxy-5-methoxyxanthone (HLT4) and HLT0 (yet to be identified). Three of the tested compounds presented significant anti-plasmodial activities (with 50% inhibitory concentration, IC50 < 5 μM), with 5-hydroxy-3-methoxyxanthone exerting the highest activity, followed by HLT0 and betulinic acid. All the compounds with significant anti-plasmodial activity were non-cytotoxic, except betulinic acid which showed a 50% cytotoxic concentration, CC50 of 25 μg/mL.

Conclusions
These findings justify the use of H. lanceolatum stem bark as anti-malarial by traditional healers of Western Cameroon, and could constitute a good basis for further studies towards development of new drug candidates or phytomedicines for malaria.
Mobile phones and head tumours. The discrepancies in cause-effect relationships in the epidemiological studies - how do they arise?
Authors: Levis Angelo G , Minicuci Nadia , Ricci Paolo , Gennaro Valerio , Garbisa Spiridione 
Published: June 2011

Abstract

Background
Whether or not there is a relationship between use of mobile phones (analogue and digital cellulars, and cordless) and head tumour risk (brain tumours, acoustic neuromas, and salivary gland tumours) is still a matter of debate; progress requires a critical analysis of the methodological elements necessary for an impartial evaluation of contradictory studies.

Methods
A close examination of the protocols and results from all case-control and cohort studies, pooled- and meta-analyses on head tumour risk for mobile phone users was carried out, and for each study the elements necessary for evaluating its reliability were identified. In addition, new meta-analyses of the literature data were undertaken. These were limited to subjects with mobile phone latency time compatible with the progression of the examined tumours, and with analysis of the laterality of head tumour localisation corresponding to the habitual laterality of mobile phone use.

Results
Blind protocols, free from errors, bias, and financial conditioning factors, give positive results that reveal a cause-effect relationship between long-term mobile phone use or latency and statistically significant increase of ipsilateral head tumour risk, with biological plausibility. Non-blind protocols, which instead are affected by errors, bias, and financial conditioning factors, give negative results with systematic underestimate of such risk. However, also in these studies a statistically significant increase in risk of ipsilateral head tumours is quite common after more than 10 years of mobile phone use or latency. The meta-analyses, our included, examining only data on ipsilateral tumours in subjects using mobile phones since or for at least 10 years, show large and statistically significant increases in risk of ipsilateral brain gliomas and acoustic neuromas.

Conclusions
Our analysis of the literature studies and of the results from meta-analyses of the significant data alone shows an almost doubling of the risk of head tumours induced by long-term mobile phone use or latency.
Nuclear and cytoplasmic LIMK1 enhances human breast cancer progression
Authors: McConnell Brice V , Koto Karen , Gutierrez-Hartmann Arthur 
Published: June 2011

Abstract

Background
LIM kinase 1 (LIMK1) is expressed in both cytoplasmic and nuclear compartments, and is a key regulator of cytoskeletal organization involved in cell migration and proliferation. LIMK1 levels are increased in several human cancers, with LIMK1 over-expression in prostate and breast cancer cells leading to tumor progression. While it has been presumed that the mechanism by which LIMK1 promotes cancer progression is via its cytoplasmic effects, the role of nuclear vs cytoplasmic LIMK1 in the tumorigenic process has not been examined.

Results
To determine if cytoplasmic or nuclear LIMK1 expression correlated with breast cancer, we performed immunohistochemical (IHC) analysis of breast tissue microarrays (TMAs), The IHC analysis of breast TMAs revealed that 76% of malignant breast tissue samples strongly expressed LIMK1 in the cytoplasm, with 52% of these specimens also expressing nuclear LIMK1. Only 48% of benign breast samples displayed strong cytoplasmic LIMK1 expression and 27% of these expressed nuclear LIMK1. To investigate the respective roles of cytoplamsic and nuclear LIMK1 in breast cancer progression, we targeted GFP-LIMK1 to cytoplasmic and nuclear subcellular compartments by fusing nuclear export signals (NESs) or nuclear localization sequences (NLS), respectively, to the amino-terminus of GFP-LIMK1. Stable pools of MDA-MB-231 cells were generated by retroviral transduction, and fluorescence microscopy revealed that GFP alone (control) and GFP-LIMK1 were each expressed in both the cytoplasm and nucleus of MDA-MB-231 cells, whereas NLS-GFP-LIMK1 was expressed in the nucleus and NES-GFP-LIMK1 was expressed in the cytoplasm. Western blot analyses revealed equal expression of GFP-LIMK1 and NES-GFP-LIMK1, with NLS-GFP-LIMK1 expression being less but equal to endogenous LIMK1. Also, Western blotting revealed increased levels of phospho-cofilin, phospho-FAK, phospho-paxillin, phospho-Src, phospho-AKT, and phospho-Erk1/2 in cells expressing all GFP-LIMK1 fusions, compared to GFP alone. Invasion assays revealed that all GFP-LIMK1 fusions increased MDA-MB-231 cell invasion ~1.5-fold, compared to GFP-only control cells. Tumor xenograft studies in nude mice revealed that MDA-MB-231 cells stably expressing GFP-LIMK, NLS-GFP-LIMK1 and NES-GFP-LIMK1 enhanced tumor growth 2.5-, 1.6- and 4.7-fold, respectively, compared to GFP-alone.

Conclusion
Taken together, these data demonstrate that LIMK1 activity in both the cytoplasmic and nuclear compartments promotes breast cancer progression, underscoring that nuclear LIMK1 contributes to the transforming function of LIMK1.
Ovarian endometriomas and IVF: a retrospective case-control study
Authors: Bongioanni Francesca , Revelli Alberto , Gennarelli Gianluca , Guidetti Daniela , Delle Piane Luisa Delle , Holte Jan 
Published: June 2011

Abstract
We performed this retrospective case-control study analyzing 428 first-attempt in vitro fertilization (IVF) cycles, among which 254 involved women with a previous or present diagnosis of ovarian endometriosis. First, the results of these 254 cycles were compared with 174 cycles involving patients with proven non-endometriotic tubal infertility having similar age and body mass index. Women with ovarian endometriosis had a significantly higher cancellation rate, but similar pregnancy, implantation and delivery rates as patients with tubal infertility. Second, among the women with ovarian endometriosis, the women with a history of laparoscopic surgery for ovarian endometriomas prior to IVF and no visual endometriosis at ovum pick-up (n = 112) were compared with the non-operated women and visual endometriomas at ovum pick-up (n = 142). Patients who underwent ovarian surgery before IVF had significantly shorter period, lower antral follicle count and required higher gonadotropin doses than patients with non-operated endometriomas. The two groups of women with a previous or present ovarian endometriosis did, however, have similar pregnancy, implantation and live birth rates. In conclusion, ovarian endometriosis does not reduce IVF outcome compared with tubal factor. Furthermore, laparoscopic removal of endometriomas does not improve IVF results, but may cause a decrease of ovarian responsiveness to gonadotropins.
Self-organized chains of nanodots induced by an off-normal incident beam
Authors: Lee Seungjun , Wang Lumin , Lu Wei 
Published: June 2011

Abstract
We propose a model to show that under off-normal bombardment of an incident ion beam, a solid surface may spontaneously form nanoscale dots lining up into chains perpendicular to the incident beam direction. These dots demonstrate a highly ordered hexagonal pattern. We attribute the self-organization behavior to surface instability under concurrent surface kinetics and to a shadow effect that causes the self-alignment of dots. The fundamental mechanism may be applicable to diverse systems, suggesting an effective approach for nanofabrication.
Modeling of polyethylene, poly(l-lactide), and CNT composites: a dissipative particle dynamics study
Authors: Wang Yao-Chun , Ju Shin-Pon , Huang Tien Jung , Wang Hung-Hsiang 
Published: June 2011

Abstract
Dissipative particle dynamics (DPD), a mesoscopic simulation approach, is used to investigate the effect of volume fraction of polyethylene (PE) and poly(l-lactide) (PLLA) on the structural property of the immiscible PE/PLLA/carbon nanotube in a system. In this work, the interaction parameter in DPD simulation, related to the Flory-Huggins interaction parameter χ, is estimated by the calculation of mixing energy for each pair of components in molecular dynamics simulation. Volume fraction and mixing methods clearly affect the equilibrated structure. Even if the volume fraction is different, micro-structures are similar when the equilibrated structures are different. Unlike the blend system, where no relationship exists between the micro-structure and the equilibrated structure, in the di-block copolymer system, the micro-structure and equilibrated structure have specific relationships.
Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy
Authors: Wong Raymond , Balachandran Ahalya , Mao Annie YQ , Dobson Wendy , Gray-Owen Scott , Cochrane Alan 
Published: June 2011

Abstract

Background
RNA processing plays a critical role in the replication of HIV-1, regulated in part through the action of host SR proteins. To explore the impact of modulating SR protein activity on virus replication, the effect of increasing or inhibiting the activity of the Cdc2-like kinase (CLK) family of SR protein kinases on HIV-1 expression and RNA processing was examined.

Results
Despite their high homology, increasing individual CLK expression had distinct effects on HIV-1, CLK1 enhancing Gag production while CLK2 inhibited the virus. Parallel studies on the anti-HIV-1 activity of CLK inhibitors revealed a similar discrepant effect on HIV-1 expression. TG003, an inhibitor of CLK1, 2 and 4, had no effect on viral Gag synthesis while chlorhexidine, a CLK2, 3 and 4 inhibitor, blocked virus production. Chlorhexidine treatment altered viral RNA processing, decreasing levels of unspliced and single spliced viral RNAs, and reduced Rev accumulation. Subsequent experiments in the context of HIV-1 replication in PBMCs confirmed the capacity of chlorhexidine to suppress virus replication.

Conclusions
Together, these findings establish that HIV-1 RNA processing can be targeted to suppress virus replication as demonstrated by manipulating individual CLK function and identified chlorhexidine as a lead compound in the development of novel anti-viral therapies.