bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation screening of ASMT, the last enzyme of the melatonin pathway, in a large sample of patients with Intellectual Disability
Authors: Pagan Cecile , Botros Hany Goubran , Poirier Karine , Dumaine Anne , Jamain Stéphane , Moreno Sarah , de Brouwer Arjan , Van Esch Hilde , Delorme Richard , Launay Jean-Marie , Tzschach Andreas , Kalscheuer Vera , Lacombe Didier , Briault Sylvain , Laumonnier Frédéric , Raynaud Martine , van Bon Bregje W , Willemsen Marjolein H , Leboyer Marion , Chelly Jamel , Bourgeron Thomas 
Published: February 2011

Abstract

Background
Intellectual disability (ID) is frequently associated with sleep disorders. Treatment with melatonin demonstrated efficacy, suggesting that, at least in a subgroup of patients, the endogenous melatonin level may not be sufficient to adequately set the sleep-wake cycles. Mutations in ASMT gene, coding the last enzyme of the melatonin pathway have been reported as a risk factor for autism spectrum disorders (ASD), which are often comorbid with ID. Thus the aim of the study was to ascertain the genetic variability of ASMT in a large cohort of patients with ID and controls.

Methods
Here, we sequenced all exons of ASMT in a sample of 361 patients with ID and 440 controls. We then measured the ASMT activity in B lymphoblastoid cell lines (BLCL) of patients with ID carrying an ASMT variant and compared it to controls.

Results
We could identify eleven variations modifying the protein sequence of ASMT (ID only: N13H, N17K, V171M, E288D; controls only: E61Q, D210G, K219R, P243L, C273S, R291Q; ID and controls: L298F) and two deleterious splice site mutations (IVS5+2T>C and IVS7+1G>T) only observed in patients with ID. We then ascertained ASMT activity in B lymphoblastoid cell lines from patients carrying the mutations and showed significantly lower enzyme activity in patients carrying mutations compared to controls (p = 0.004).

Conclusions
We could identify patients with deleterious ASMT mutations as well as decreased ASMT activity. However, this study does not support ASMT as a causative gene for ID since we observed no significant enrichment in the frequency of ASMT variants in ID compared to controls. Nevertheless, given the impact of sleep difficulties in patients with ID, melatonin supplementation might be of great benefit for a subgroup of patients with low melatonin synthesis.
A validation of the first genome-wide association study of calcaneus ultrasound parameters in the European Male Ageing Study
Authors: Roshandel Delnaz , Thomson Wendy , Pye Stephen R , Boonen Steven , Borghs Herman , Vanderschueren Dirk , Huhtaniemi Ilpo T , Adams Judith E , Ward Kate A , Bartfai Gyorgy , Casanueva Felipe , Finn Joseph D , Forti Gianni , Giwercman Aleksander , Han Thang S , Kula Krzysztof , Lean Michael E , Pendleton Neil , Punab Margus , Silman Alan J , Wu Frederick C , Holliday Kate L , O'Neill Terence W ,   The EMAS Study Group
Published: February 2011

Abstract

Background
A number of single nucleotide polymorphisms (SNPs) have been associated with broadband ultrasound attenuation (BUA) and speed of sound (SOS) as measured by quantitative ultrasound (QUS) at the calcaneus in the Framingham 100K genome-wide association study (GWAS) but have not been validated in independent studies. The aim of this analysis was to determine if these SNPs are associated with QUS measurements assessed in a large independent population of European middle-aged and elderly men. The association between these SNPs and bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DXA) was also tested.

Methods
Men aged 40-79 years (N = 2960) were recruited from population registers in seven European centres for participation in an observational study of male ageing, the European Male Ageing Study (EMAS). QUS at the calcaneus was measured in all subjects and blood was taken for genetic analysis. Lumbar spine (LS), femoral neck (FN) and total hip (TH) BMD were measured by DXA in a subsample of 620 men in two centres. SNPs associated with BUA or SOS in the Framingham study with p < 10-4 were selected and genotyped using SEQUENOM technology. Linear regression was used to test for the association between SNPs and standardised (SD) bone outcomes under an additive genetic model adjusting for centre. The same direction of effect and p < 0.05 indicated replication.

Results
Thirty-four of 38 selected SNPs were successfully genotyped in 2377 men. Suggestive evidence of replication was observed for a single SNP, rs3754032, which was associated with a higher SOS (β(SD) = 0.07, p = 0.032) but not BUA (β(SD) = 0.02, p = 0.505) and is located in the 3'UTR of WDR77 (WD repeat domain 77) also known as androgen receptor cofactor p44. A single SNP, rs238358, was associated with BMD at the LS (β(SD) = -0.22, p = 0.014), FN (β(SD) = -0.31,p = 0.001) and TH (β(SD) = -0.36, p = 0.002) in a locus previously associated with LS BMD in large-scale GWAS, incorporating AKAP11 and RANKL.

Conclusions
We found suggestive evidence of association between a single SNP located in the 3'UTR of WDR77 with calcaneal ultrasound parameters. The majority of SNPs, associated with QUS parameters in the Framingham Study, were not replicated in an independent population sample of European men.
Acute/subacute cerebral infarction (ASCI) in HIV-negative adults with cryptococcal meningoencephalitis (CM): a MRI-based follow-up study and a clinical comparison to HIV-negative CM adults without ASCI
Authors: Chen Shu-Fang , Lu Cheng-Hsien , Lui Chun-Chung , Huang Chi-Ren , Chuang Yao-Chung , Tan Teng-Yeow , Tsai Nai-Wen , Chang Chiung-Chih , Tsai Wan-Chen , Chang Wen-Neng 
Published: February 2011

Abstract

Background
Acute/subacute cerebral infarction (ASCI) in HIV-negative cryptococcal meningoencephalitis (CM) adults has rarely been examined by a series of MRI-based follow-up study. We studied a series of MRI follow-up study of CM adults and compared the clinical characters of those with ASCI and those without ASCI.

Methods
The clinical characteristics and a series of brain MRI findings of seven CM adults with ASCI were enrolled for analysis. The clinical characteristics of another 30 HIV-negative CM adults who did not have ASCI were also included for a comparative analysis.

Results
The seven HIV-negative CM adults with ASCI were four men and three women, aged 46-78 years. Lacunar infarction was the type of ASCI, and 86% (6/7) of the ACSI were multiple infarctions distributed in both the anterior and posterior cerebrovascular territories. The seven CM patients with ASCI were significantly older and had a higher rate of DM and previous stroke than the other 30 CM adults without ASCI. They also had a higher incidence of consciousness disturbance at presentation and had a poor prognosis.

Conclusion
ASCI was found in 18.9% (7/37) of HIV-negative CM adults. Serial MRI follow-up studies may allow a better delineation of ASCI in this specific group of infectious disease and multiple lacunar infarctions was the most common type. Older in age and presence of DM and previous stroke were the significant underlying conditions. CM patients with ASCI also had a poor therapeutic outcome.
Use of cerebral state index to predict long-term unconsciousness in patients after elective craniotomy with delay recovery
Authors: Xu Ming , Lei Yan-Ni , Zhou Jian-Xin 
Published: February 2011

Abstract

Background
The major difficulty in postoperative care in patients after craniotomy is to distinguish the intracranial deficits from the residual effect of general anesthesia. In present study, we used cerebral state index (CSI) monitoring in patients after craniotomy with delayed recovery, and evaluated the prediction probability of CSI for long-term postoperative unconsciousness.

Methods
We enrolled 57 consecutive adult patients admitted to neurosurgical intensive care unit (NICU) after elective craniotomy with delayed recovery. CSI was continuously monitored for 6 hours after admission. Patient's level of consciousness was followed up for 24 hours. According to whether obeyed verbal command, patients were divided into awaken group and non-awaken group. CSI values were compared between the two groups. Prediction probability (PK) was calculated to determine the probability of CSI in predicting unconsciousness 24 hours after operation.

Results
In awaken group (n = 51), CSI increased significantly after the 2nd NICU admitted hour (P < 0.05). At each time point, CSI values in awaken group were significantly higher than those in non-awaken group (n = 6) (P < 0.05). The values of PK (SE) for CSI in the first 6 admitted hours ranged from 0.94 (0.06) to 0.99 (0.02).

Conclusions
In patients after craniotomy with delayed recovery, CSI monitoring in early postoperative hours had high prediction probability for long-term unconsciousness. CSI monitoring may be a reliable objective method to predict level of consciousness after elective craniotomy.
Expression profile of the N-myc Downstream Regulated Gene 2 (NDRG2) in human cancers with focus on breast cancer
Authors: Lorentzen Anders , Lewinsky Rikke H , Bornholdt Jette , Vogel Lotte K , Mitchelmore Cathy 
Published: February 2011

Abstract

Background
Several studies have shown that NDRG2 mRNA is down-regulated or undetectable in various human cancers and cancer cell-lines. Although the function of NDRG2 is currently unknown, high NDRG2 expression correlates with improved prognosis in high-grade gliomas, gastric cancer and hepatocellular carcinomas. Furthermore, in vitro studies have revealed that over-expression of NDRG2 in cell-lines causes a significant reduction in their growth. The aim of this study was to examine levels of NDRG2 mRNA in several human cancers, with focus on breast cancer, by examining affected and normal tissue.

Methods
By labelling a human Cancer Profiling Array with a radioactive probe against NDRG2, we evaluated the level of NDRG2 mRNA in 154 paired normal and tumor samples encompassing 19 different human cancers. Furthermore, we used quantitative real-time RT-PCR to quantify the levels of NDRG2 and MYC mRNA in thyroid gland cancer and breast cancer, using a distinct set of normal and tumor samples.

Results
From the Cancer Profiling Array, we saw that the level of NDRG2 mRNA was reduced by at least 2-fold in almost a third of the tumor samples, compared to the normal counterpart, and we observed a marked decreased level in colon, cervix, thyroid gland and testis. However, a Benjamini-Hochberg correction showed that none of the tissues showed a significant reduction in NDRG2 mRNA expression in tumor tissue compared to normal tissue. Using quantitative RT-PCR, we observed a significant reduction in the level of NDRG2 mRNA in a distinct set of tumor samples from both thyroid gland cancer (p = 0.02) and breast cancer (p = 0.004), compared with normal tissue. MYC mRNA was not significantly altered in breast cancer or in thyroid gland cancer, compared with normal tissue. In thyroid gland, no correlation was found between MYC and NDRG2 mRNA levels, but in breast tissue we found a weakly significant correlation with a positive r-value in both normal and tumor tissues, suggesting that MYC and NDRG2 mRNA are regulated together.

Conclusion
Expression of NDRG2 mRNA is reduced in many different human cancers. Using quantitative RT-PCR, we have verified a reduction in thyroid cancer and shown, for the first time, that NDRG2 mRNA is statistically significantly down-regulated in breast cancer. Furthermore, our observations indicate that other tissues such as cervix and testis can have lower levels of NDRG2 mRNA in tumor tissue compared to normal tissue.
Modulation of TRAIL resistance in colon carcinoma cells: Different contributions of DR4 and DR5
Authors: van Geelen Caroline MM , Pennarun Bodvael , Le Phuong TK , de Vries Elisabeth GE , de Jong Steven 
Published: February 2011

AbstractBackgroundrhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5). Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether agonistic DR4 or DR5 antibodies could be used to circumvent rhTRAIL resistance, alone or in combination with various chemotherapies.MethodsOur study was performed in an isogenic model comprised of the SW948 human colon carcinoma cell line and its rhTRAIL resistant sub-line SW948-TR. Effects of rhTRAIL and agonistic DR4/DR5 antibodies on cell viability were measured using MTT assays and identification of morphological changes characteristic of apoptosis, after acridine orange staining. Sensitivity to the different death receptor ligands was stimulated using pretreatment with the cytokine IFN-gamma and the proteasome inhibitor MG-132. To investigate the mechanisms underlying the changes in rhTRAIL sensitivity, alterations in expression levels of targets of interest were measured by Western blot analysis. Co-immunoprecipitation was used to determine the composition of the death-inducing signalling complex at the cell membrane.ResultsSW948 cells were sensitive to all three of the DR-targeting agents tested, although the agonistic DR5 antibody induced only weak caspase 8 cleavage and limited apoptosis. Surprisingly, agonistic DR4 and DR5 antibodies induced equivalent DISC formation and caspase 8 cleavage at the level of their individual receptors, suggesting impairment of further caspase 8 processing upon DR5 stimulation. SW948-TR cells were cross-resistant to all DR-targeting agents as a result of decreased caspase 8 expression levels. Caspase 8 protein expression was restored by MG-132 and IFN-gamma pretreatment, which also re-established sensitivity to rhTRAIL and agonistic DR4 antibody in SW948-TR. Surprisingly, MG-132 but not IFN-gamma could also increase DR5-mediated apoptosis in SW948-TR.ConclusionsThese results highlight a critical difference between DR4- and DR5-mediated apoptotic signaling modulation, with possible implications for future combinatorial regimens.
A randomised trial of a psychosocial intervention for cancer patients integrated into routine care: the PROMPT study (promoting optimal outcomes in mood through tailored psychosocial therapies)
Authors: Turner Jane , Kelly Brian , Clarke David , Yates Patsy , Aranda Sanchia , Jolley Damien , Chambers Suzanne , Hargraves Maryanne , McFadyen Lisa 
Published: February 2011

Abstract

Background
Despite evidence that up to 35% of patients with cancer experience significant distress, access to effective psychosocial care is limited by lack of systematic approaches to assessment, a paucity of psychosocial services, and patient reluctance to accept treatment either because of perceived stigma or difficulties with access to specialist psycho-oncology services due to isolation or disease burden. This paper presents an overview of a randomised study to evaluate the effectiveness of a brief tailored psychosocial Intervention delivered by health professionals in cancer care who undergo focused training and participate in clinical supervision.

Methods/design
Health professionals from the disciplines of nursing, occupational therapy, speech pathology, dietetics, physiotherapy or radiation therapy will participate in training to deliver the psychosocial Intervention focusing on core concepts of supportive-expressive, cognitive and dignity-conserving care. Health professional training will consist of completion of a self-directed manual and participation in a skills development session. Participating health professionals will be supported through structured clinical supervision whilst delivering the Intervention. In the stepped wedge design each of the 5 participating clinical sites will be allocated in random order from Control condition to Training then delivery of the Intervention. A total of 600 patients will be recruited across all sites. Based on level of distress or risk factors eligible patients will receive up to 4 sessions, each of up to 30 minutes in length, delivered face-to-face or by telephone. Participants will be assessed at baseline and 10-week follow-up. Patient outcome measures include anxiety and depression, quality of life, unmet psychological and supportive care needs. Health professional measures include psychological morbidity, stress and burnout. Process evaluation will be conducted to assess perceptions of participation in the study and the factors that may promote translation of learning into practice.

Discussion
This study will provide important information about the effectiveness of a brief tailored psychological Intervention for patients with cancer and the potential to prevent development of significant distress in patients considered at risk. It will yield data about the feasibility of this model of care in routine clinical practice and identify enablers and barriers to its systematic implementation in cancer settings.

Trial registration

ACTRN12610000448044
Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines
Authors: Abe Masako , Havre Pamela A , Urasaki Yasuyo , Ohnuma Kei , Morimoto Chikao , Dang Long H , Dang Nam H 
Published: February 2011

Abstract

Background
CD26 (dipeptidyl peptidase IV, DPPIV) is a 110 kDa surface glycoprotein expressed in most normal tissues, and is a potential novel therapeutic target for selected cancers. Our work evaluates the mechanism involved in confluence-dependent CD26 expression in colon cancer.

Methods
Colon adenocarcinoma cells were grown to confluence, and expression of CD26 and transcription factors implicated in its regulation was confirmed by immunofluorescence and Western blotting. Real-time PCR was also performed to evaluate CD26 upregulation at the transcriptional level. The influence of c-Myc on CD26 expression during different growth conditions was further evaluated following transient transfection of a c-Myc-expressing plasmid and a c-Myc specific siRNA.

Results
We found that the colon cancer cell lines HCT-116 and HCT-15 exhibited a confluence-dependent increase in CD26 mRNA and protein, associated with decreased expression of c-Myc, increased USF-1 and Cdx 2 levels, and unchanged HNF-1α expression. Meanwhile, ectopic expression of c-Myc in both cell lines led to decreased CD26 expression. In contrast, transfection of a siRNA targeted to Cdx2 resulted in decreased CD26 level. Importantly, culturing of cells in serum-depleted media, but not acidic conditions, upregulated CD26. While HIF-1α level also increased when cells were cultured in serum-depleted media, its expression was required but not sufficient for CD26 upregulation.

Conclusions
CD26 mRNA and protein levels increase in a confluence-dependent manner in colon carcinoma cell lines, with c-Myc acting as a repressor and Cdx2 acting as an enhancer of CD26 expression. The enhanced expression of CD26 in serum-depleted media and a requirement for HIF-1α suggest a role for nutrients or growth factors in the regulation of CD26 protein expression.
Isolated sixth cranial nerve palsy as the presenting symptom of a rapidly expanding ACTH positive pituitary adenoma: a case report
Authors: Saffra Norman , Kaplow Elizabeth , Mikolaenko Irina , Kim Alice , Rubin Benjamin , Jafar Jafar 
Published: February 2011

Abstract

Background
Pituitary adenoma may present with neuro-ophthalmic manifestations and, typically, rapid tumor expansion is the result of apoplexy. Herein, we present the first case of an isolated sixth cranial nerve palsy as initial feature of a rapidly expanding ACTH positive silent tumor without apoplexy.

Case Presentation
A 44 year old female with a history of sarcoidosis presented with an isolated sixth cranial nerve palsy as the initial clinical feature of a rapidly expanding ACTH positive silent pituitary adenoma. The patient underwent emergent transsphenoidal hypophysectomy for this rapidly progressive tumor and subsequently regained complete vision and ocular motility. Despite tumor extension into the cavernous sinus, the other cranial nerves were spared during the initial presentation.

Conclusions
This case illustrates the need to consider a rapidly growing pituitary tumor as a possibility when presented with a rapidly progressive ophthalmoplegia.
The intersection between sex and drugs: a cross-sectional study among the spouses of injection drug users in Chennai, India
Authors: Solomon Sunil S , Srikrishnan Aylur K , Celentano David D , Johnson Sethulakshmi C , Vasudevan Canjeevaram K , Murugavel Kailapuri G , Anand Santhanam , Kumar M Suresh , Solomon Suniti , Mehta Shruti H 
Published: February 2011

AbstractBackgroundIt is estimated that there are up to 1.1 million injection drug users (IDUs) in India; the majority are likely married. We characterize HIV, hepatitis B (HBV) and hepatitis C (HCV) prevalence and the risk environment of a sample of spouses of IDUs.MethodsA cohort of 1158 IDUs (99% male) was recruited in Chennai, India from 2005-06. A convenience sample of 400 spouses of the male IDUs in this cohort was recruited in 2009. A risk assessment questionnaire was administered and a blood sample collected. Logistic regression was used to identify factors associated with prevalent HIV.ResultsMedian age was 31 years; thirteen percent were widowed and 7% were not currently living with their spouse. Only 4 (1%) reported ever injecting drugs; Twenty-two percent and 25% reported ever using non-injection drugs and alcohol, respectively. The majority had one lifetime sexual partner and 37 (9%) reporting exchanging sex. Only 7% always used condoms with their regular partner. HIV, HBV and HCV prevalence were 2.5%, 3.8% and 0.5%, respectively; among spouses of HIV+ IDUs (n = 78), HIV prevalence was 10.3%. The strongest predictor of HIV was spousal HIV status (OR: 17.9; p < 0.001). Fifty-six percent of women had ever experienced intimate partner violence; Eight-six percent reported sexual violence.ConclusionsOur finding of a 10-fold higher HIV prevalence among spouses of IDUs compared with general population women indicates their vulnerability; prevalence is likely to increase given the context of low condom use and frequent sexual violence. Prevention efforts directed at IDUs should also include programs for spouses.