bluuebunny/crossref_metadata_2025 huggingface dataset:
No association of the polymorphisms of the frizzled-related protein gene with peak bone mineral density in Chinese nuclear families
Authors: Gao Gao , Zhang Zhen-Lin , He Jin-Wei , Zhang Hao , Yue Hua , Hu Wei-Wei , Gu Jie-Mei , Fu Wen-Zhen , Hu Yun-Qiu , Li Miao , Liu Yu-Juan , Yu Jin-Bo
Published: January 2010

Background

The Wnt/beta-catenin signaling pathway plays an important role in skeletal development. Polymorphisms of frizzled-related protein (FRZB), an antagonist of this pathway, may generate variations in bone mineral density (BMD). In this study, we analyzed the association between FRZB genotypes and peak BMD variation in the spines and hips of two relatively large samples of Chinese female-offspring and male-offspring nuclear families.

Methods

We recruited 1,260 subjects from 401 female-offspring nuclear families and 1,296 subjects from 427 male-offspring nuclear families and genotyped four tagging single nucleotide polymorphisms (tagSNPs) (rs6433993, rs409238, rs288324, and rs4666865) spanning the entire FRZB gene. The SNPs rs288326 and rs7775, which are associated with hip osteoarthritis, were not selected in this study because of their low minor allele frequencies (MAFs) in Chinese people. The quantitative transmission disequilibrium test (QTDT) was used to analyze the association between each SNP and haplotype with peak BMD in female- and male-offspring nuclear families.

Results

In the female-offspring nuclear families, we found no evidence of an association between either single SNPs or haplotypes and peak BMD in the spine or hip. In the male-offspring nuclear families, no within-family association was observed for either SNPs or haplotypes, although a significant total association was found between rs4666865 and spine BMD (P = 0.0299).

Conclusion

Our results suggest that natural variation in FRZB is not a major contributor to the observed variability in peak BMD in either Chinese females or males. Because ethnic differences in the FRZB genotypes may exist, other studies in different population are required to confirm such results.
Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity
Authors: Müller Timo D , Brönner Günter , Wandolski Melanie , Carrie Jophia , Nguyen Trang T , Greene Brandon H , Scherag André , Grallert Harald , Vogel Carla IG , Scherag Susann , Rief Winfried , Wichmann Hans-Erich , Illig Thomas , Schäfer Helmut , Hebebrand Johannes , Hinney Anke
Published: January 2010

Background

The orexigenic effects of cannabinoids are limited by activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). The aim of this study was to analyse whether FAAH alleles are associated with early and late onset obesity.

Methods

We initially assessed association of five single nucleotide polymorphisms (SNPs) in FAAH with early onset extreme obesity in up to 521 German obese children and both parents. SNPs with nominal p-values ≤ 0.1 were subsequently analysed in 235 independent German obesity families. SNPs associated with childhood obesity (p-values ≤ 0.05) were further analysed in 8,491 adult individuals of a population-based cohort (KORA) for association with adult obesity. One SNP was further analysed in 985 German obese adults and 588 normal and underweight controls. In parallel, we screened the FAAH coding region for novel sequence variants in 92 extremely obese children using single-stranded-conformation-polymorphism-analysis and denaturing HPLC and assessed the implication of the identified new variants for childhood obesity.

Results

The trio analysis revealed some evidence for an association of three SNPs in FAAH (rs324420 rs324419 and rs873978) with childhood obesity (two-sided p-values between 0.06 and 0.10). Although analyses of these variants in 235 independent obesity families did not result in statistically significant effects (two-sided p-values between 0.14 and 0.75), the combined analysis of all 603 obesity families supported the idea of an association of two SNPs in FAAH (rs324420 and rs2295632) with early onset extreme obesity (p-values between 0.02 and 0.03). No association was, however, found between these variants and adult obesity. The mutation screen revealed four novel variants, which were not associated with early onset obesity (p > 0.05).

Conclusions

As we observed some evidence for an association of the FAAH variants rs2295632 rs324420 with early onset but not adult obesity, we conclude that the FAAH variants analyzed here at least do not seem to play a major role in the etiology of obesity within our samples.
Genetic diversity among Plasmodium falciparum field isolates in Pakistan measured with PCR genotyping of the merozoite surface protein 1 and 2
Authors: Ghanchi Najia K , Mårtensson Andreas , Ursing Johan , Jafri Sana , Bereczky Sándor , Hussain Rabia , Beg Mohammad A
Published: January 2010

Background

The genetic diversity of Plasmodium falciparum has been extensively studied in various parts of the world. However, limited data are available from Pakistan. This study aimed to establish molecular characterization of P. falciparum field isolates in Pakistan measured with two highly polymorphic genetic markers, i.e. the merozoite surface protein 1 (msp-1)and 2 (msp-2).

Methods

Between October 2005 and October 2007, 244 blood samples from patients with symptomatic blood-slide confirmed P. falciparum mono-infections attending the Aga Khan University Hospital, Karachi, or its collection units located in Sindh and Baluchistan provinces, Pakistan were collected. The genetic diversity of P. falciparum was analysed by length polymorphism following gel electrophoresis of DNA products from nested polymerase chain reactions (PCR) targeting block 2 of msp-1 and block 3 of msp-2, including their respective allelic families KI, MAD 20, RO33, and FC27, 3D7/IC.

Results

A total of 238/244 (98%) patients had a positive PCR outcome in at least one genetic marker; the remaining six were excluded from analysis. A majority of patients had monoclonal infections. Only 56/231 (24%) and 51/236 (22%) carried multiple P. falciparum genotypes in msp-1 and msp-2, respectively. The estimated total number of genotypes was 25 msp-1 (12 KI; 8 MAD20; 5 RO33) and 33 msp-2 (14 FC27; 19 3D7/IC).

Conclusions

This is the first report on molecular characterization of P. falciparum field isolates in Pakistan with regards to multiplicity of infection. The genetic diversity and allelic distribution found in this study is similar to previous reports from India and Southeast Asian countries with low malaria endemicity.
Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors
Authors: Landais Igor , Hiddingh Sanne , McCarroll Matthew , Yang Chao , Sun Aiming , Turker Mitchell S , Snyder James P , Hoatlin Maureen E
Published: December 2009

Background

The Fanconi anemia (FA) pathway is a multigene DNA damage response network implicated in the repair of DNA lesions that arise during replication or after exogenous DNA damage. The FA pathway displays synthetic lethal relationship with certain DNA repair genes such as ATM (Ataxia Telangectasia Mutated) that are frequently mutated in tumors. Thus, inhibition of FANCD2 monoubiquitylation (FANCD2-Ub), a key step in the FA pathway, might target tumor cells defective in ATM through synthetic lethal interaction. Curcumin was previously identified as a weak inhibitor of FANCD2-Ub. The aim of this study is to identify derivatives of curcumin with better activity and specificity.

Results

Using a replication-free assay in Xenopus extracts, we screened monoketone analogs of curcumin for inhibition of FANCD2-Ub and identified analog EF24 as a strong inhibitor. Mechanistic studies suggest that EF24 targets the FA pathway through inhibition of the NF-kB pathway kinase IKK. In HeLa cells, nanomolar concentrations of EF24 inhibited hydroxyurea (HU)-induced FANCD2-Ub and foci in a cell-cycle independent manner. Survival assays revealed that EF24 specifically sensitizes FA-competent cells to the DNA crosslinking agent mitomycin C (MMC). In addition, in contrast with curcumin, ATM-deficient cells are twofold more sensitive to EF24 than matched wild-type cells, consistent with a synthetic lethal effect between FA pathway inhibition and ATM deficiency. An independent screen identified 4H-TTD, a compound structurally related to EF24 that displays similar activity in egg extracts and in cells.

Conclusions

These results suggest that monoketone analogs of curcumin are potent inhibitors of the FA pathway and constitute a promising new class of targeted anticancer compounds.
Quantum dots improve peptide detection in MALDI MS in a size dependent manner
Authors: Bailes Julian , Vidal Loïc , Ivanov Dimitri A , Soloviev Mikhail
Published: December 2009

Laser Desorption Ionization Mass Spectrometry employs matrix which is co-crystallised with the analyte to achieve "soft ionization" that is the formation of ions without fragmentation. A variety of matrix-free and matrix-assisted LDI techniques and matrices have been reported to date. LDI has been achieved using ultra fine metal powders (UFMPs), desorption ionisation on silicon (DIOS), sol-gel assisted laser desorption/ionization (SGALDI), as well as with common MALDI matrices such as 2,5-dihydroxy benzoic acid (DHB), 3,5-dimethoxy-4-hydroxycinnamic acid (SA), α-cyano-4-hydroxycinnamic acid (CHCA) to name a few. A variety of matrix additives have been shown to improve matrix assisted desorption, including silicon nanowires (SiNW), carbon nanotubes (CNT), metal nanoparticles and nanodots. To our knowledge no evidence exists for the application of highly fluorescent CdSe/ZnS quantum dots to enhance MALDI desorption of biological samples. Here we report that although CdSe/ZnS quantum dots on their own can not substitute matrix in MALDI-MS, their presence has a moderately positive effect on MALDI desorption, improves the signal-to-noise ratio, peak quality and increases the number of detected peptides and the overall sequence coverage.
Excitatory and inhibitory effects of prolactin release activated by nerve stimulation in rat anterior pituitary
Authors: Zhang Ping , Liu Ling , Xie Cong-Jun , Wang Kai-Hu , Gao Li-Zhi , Ju Gong
Published: December 2009

Background

A series of studies showed the presence of substantial amount of nerve fibers and their close relationship with the anterior pituitary gland cells. Our previous studies have suggested that aside from the classical theory of humoral regulation, the rat anterior pituitary has direct neural regulation on adrenocorticotropic hormone release. In rat anterior pituitary, typical synapses are found on every type of the hormone-secreting cells, many on lactotrophs. The present study was aimed at investigating the physiological significance of this synaptic relationship on prolactin release.

Methods

The anterior pituitary of rat was sliced and stimulated with electrical field in a self-designed perfusion chamber. The perfusate was continuously collected in aliquots and measured by radioimmunoassay for prolactin levels. After statistic analysis, differences of prolactin concentrations within and between groups were outlined.

Results

The results showed that stimulation at frequency of 2 Hz caused a quick enhancement of prolactin release, when stimulated at 10 Hz, prolactin release was found to be inhibited which came slower and lasted longer. The effect of nerve stimulation on prolactin release is diphasic and frequency dependent.

Conclusions

The present in vitro study offers the first physiological evidence that stimulation of nerve fibers can affect prolactin release in rat anterior pituitary. Low frequency stimulation enhances prolactin release and high frequency mainly inhibits it.
Estrogen and inflammation modulate estrogen receptor alpha expression in specific tissues of the temporomandibular joint
Authors: Puri Jyoti , Hutchins Bob , Bellinger Larry L , Kramer Phillip R
Published: December 2009

Background

Estrogen is known to play role in temporomandibular joint (TMJ) disorders and estrogen effects can be mediated by estrogen receptor (ER) alpha present in the TMJ. Cells expressing the estrogen receptor ERalpha are present in the temporomandibular joint (TMJ) but changes in expression due to estrogen and inflammation have not been characterized. In this study, ERalpha protein content and the number of cells expressing ERalpha was measured in 17 beta-estradiol-treated rats after inflammation was induced in the TMJ.

Methods

Sixteen ovariectomized female rats were divided into two groups such that one group received 17 beta estradiol (E2) and the other was given vehicle (VEH). Groups were then subdivided further, one received injections of saline and the other received Complete Freund's adjuvant (CFA) within the superior joint space of the TMJ. Thus the four groups include no E2/saline, E2/saline, no E2/CFA and E2/CFA. After treatment, the rats were sacrificed, and the TMJ anterior, disc, retrodiscal and synovial tissues were analyzed by western blot and immunocytochemistry. Positive stained cells were counted using a Nikon epifluorescent microscope.

Results

The western blot showed that ERalpha protein significantly decreased with inflammation. The number of ERalpha-positive cells in the TMJ was not affected by inflammation or 17 beta-estradiol with exception of the retrodiscal tissue. In the retrodiscal tissue 17 beta-estradiol significantly decreased the number of ERalpha-positive cells but only in a non-inflamed joint.

Conclusions

In conclusion, inflammation and 17 beta-estradiol can modulate ERalpha expression in the TMJ but the effects are tissue specific.
Retroviral vectors encoding ADA regulatory locus control region provide enhanced T-cell-specific transgene expression
Authors: Trinh Alice T , Ball Bret G , Weber Erin , Gallaher Timothy K , Gluzman-Poltorak Zoya , Anderson French , Basile Lena A
Published: December 2009

Background

Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone.

Methods

A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection.

Results

Vectors that contained the ADA LCR were preferentially expressed in T-cell lines. Further improvements in T-cell specific gene expression were observed with the incorporation of additional cis-regulatory elements, such as a human polyadenylation signal and intron 7 from the human ADA gene.

Conclusion

These studies suggest that the combination of an authentically regulated ADA gene in a murine retroviral vector, together with additional locus-specific regulatory refinements, will yield a vector with a safer profile and greater efficacy in terms of high-level, therapeutic, regulated gene expression for the treatment of ADA-deficient severe combined immunodeficiency.
IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients
Authors: Rajski Michal , Zanetti-Dällenbach Rosanna , Vogel Brigitte , Herrmann Richard , Rochlitz Christoph , Buess Martin
Published: January 2010

Background

Insulin-like growth factor-1 (IGF-I) signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately.

Methods

We used an ex vivo culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. In vitro data were correlated with in vivo findings by comparing the results with published expression datasets on human cancer biopsies.

Results

Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (P = 0.029 - Norway/Stanford and P = 7.96e-09 - NKI dataset). Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (P = 0.007 - Bhattacharjee and P = 0.008 - Garber dataset).

Conclusion

Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies.

See the related commentary by Werner and Bruchim: http://www.biomedcentral.com/1741-7015/8/2
Particle length-dependent titanium dioxide nanomaterials toxicity and bioactivity
Authors: Hamilton Raymond F , Wu Nianqiang , Porter Dale , Buford Mary , Wolfarth Michael , Holian Andrij
Published: December 2009

Background

Titanium dioxide (TiO2) nanomaterials have considerable beneficial uses as photocatalysts and solar cells. It has been established for many years that pigment-grade TiO2 (200 nm sphere) is relatively inert when internalized into a biological model system (in vivo or in vitro). For this reason, TiO2 nanomaterials are considered an attractive alternative in applications where biological exposures will occur. Unfortunately, metal oxides on the nanoscale (one dimension < 100 nm) may or may not exhibit the same toxic potential as the original material. A further complicating issue is the effect of modifying or engineering of the nanomaterial to be structurally and geometrically different from the original material.

Results

TiO2 nanospheres, short (< 5 μm) and long (> 15 μm) nanobelts were synthesized, characterized and tested for biological activity using primary murine alveolar macrophages and in vivo in mice. This study demonstrates that alteration of anatase TiO2 nanomaterial into a fibre structure of greater than 15 μm creates a highly toxic particle and initiates an inflammatory response by alveolar macrophages. These fibre-shaped nanomaterials induced inflammasome activation and release of inflammatory cytokines through a cathepsin B-mediated mechanism. Consequently, long TiO2 nanobelts interact with lung macrophages in a manner very similar to asbestos or silica.

Conclusions

These observations suggest that any modification of a nanomaterial, resulting in a wire, fibre, belt or tube, be tested for pathogenic potential. As this study demonstrates, toxicity and pathogenic potential change dramatically as the shape of the material is altered into one that a phagocytic cell has difficulty processing, resulting in lysosomal disruption.
Microdialysis assessment of peripheral metabolism in critical limb ischemia after endovascular revascularization
Authors: Tozzi Matteo , Muscianisi Elisa , Piffaretti Gabriele , Castelli Patrizio
Published: December 2009

Background

Critical limb ischemia is a chronic pathologic condition defined by the lack of blood flow in peripheral circulation. Microdialysis is a well-known and sensitive method for the early detection of tissue ischemia. The aim of the present study was to use microdialysis in order to analyse cellular metabolism changes after peripheral endovascular revascularization.

Methods

Ten patients diagnosed with critical limb ischemia was enrolled. CMA 60 (CMA® - Solna, Sweden) catheter with a 20 kDa cut-off was placed subcutaneously on the anterior aspect of the foot of both limbs. Samples were collected starting 12-hours before surgery and throughout the following 72-hours, using a CMA 600 (CMA® - Solna, Sweden) microdialysis analyser.

Results

Technical revascularization was successful in all cases. The cannulation was well tolerated in all patients. The site of catheter insertion healed easily in few days without infective complications in any case. Two patients underwent major amputation. After revascularization, glucose showed a strong increase (mean, 5.86 ± 1.52 mMol/L, p = .008). No restoration of the circadian rhythm was noted in patients who underwent major amputation. Glycerol concentration curves were not deductibles in both the ischemic and the control limbs (mean, 148.43 ± 42.13 mMol/L vs 178.44 ± 75.93 mMol/L, p = .348). Within the first 24-hours after revascularization, lactate concentration raised strongly (6.58 ± 1.56 mMol/L, p = .002): thereafter, it immediately decreased to a concentration similar to the control level (1.71 ± 1.69 mMol/L). In both patients who underwent major amputation, lactate did not show the typical peak of the successful revascularization. The trend of the lactate/pyruvate ratio after a brief initial decrease of the ratio increased again in both the patients who finally underwent amputation.

Conclusions

Restoration of glucose and glycerol circadian rhythm, coupled with low lactate concentration and lactate/pyruvate ratio seemed to be linked to good surgical outcome.
A computational approach to resolve cell level contributions to early glandular epithelial cancer progression
Authors: Kim Sean HJ , Debnath Jayanta , Mostov Keith , Park Sunwoo , Hunt C Anthony
Published: December 2009

Background

Three-dimensional (3D) embedded cell cultures provide an appropriate physiological environment to reconstruct features of early glandular epithelial cancer. Although these are orders of magnitude simpler than tissues, they too are complex systems that have proven challenging to understand. We used agent-based, discrete event simulation modeling methods to build working hypotheses of mechanisms of epithelial 3D culture phenotype and early cancer progression. Starting with an earlier software analogue, we validated an improved in silico epithelial analogue (ISEA) for cardinal features of a normally developed MDCK cyst. A set of axiomatic operating principles defined simulated cell actions. We explored selective disruption of individual simulated cell actions. New framework features enabled recording detailed measures of ISEA cell activities and morphology.

Results

Enabled by a small set of cell operating principles, ISEA cells multiplied and self-organized into cyst-like structures that mimicked those of MDCK cells in a 3D embedded cell culture. Selective disruption of "anoikis" or directional cell division caused the ISEA to develop phenotypic features resembling those of in vitro tumor reconstruction models and cancerous tissues in vivo. Disrupting either process, or both, altered cell activity patterns that resulted in morphologically similar outcomes. Increased disruption led to a prolonged presence of intraluminal cells.

Conclusions

ISEA mechanisms, behaviors, and morphological properties may have biological counterparts. To the extent that in silico-to-in vitro mappings are valid, the results suggest plausible, additional mechanisms of in vitro cancer reconstruction or reversion, and raise potentially significant implications for early cancer diagnosis based on histology. Further ISEA development and use are expected to provide a viable platform to complement in vitro methods for unraveling the mechanistic basis of epithelial morphogenesis and cancer progression.
Clostridium septicum infection of hepatic metastases following alcohol injection: a case report
Authors: Saleh Neam , Sohail Muhammad R , Hashmey Rayhan H , Al Kaabi Mohammed
Published: January 2010

Clostridium septicum infections are generally associated with gastrointestinal or hematologic malignancies. We report the first case of hepatic metastases infection with Clostridium septicum that followed alcohol injection of liver lesion. Clinicians should consider this possibility in patients with underlying malignancy who present with hepatic abscess, as prompt surgical drainage and empiric antibiotics may be life saving.
Genomic characterization of the Yersinia genus
Authors: Chen Peter E , Cook Christopher , Stewart Andrew C , Nagarajan Niranjan , Sommer Dan D , Pop Mihai , Thomason Brendan , Thomason Maureen P Kiley , Lentz Shannon , Nolan Nichole , Sozhamannan Shanmuga , Sulakvelidze Alexander , Mateczun Alfred , Du Lei , Zwick Michael E , Read Timothy D
Published: January 2010

Background

New DNA sequencing technologies have enabled detailed comparative genomic analyses of entire genera of bacterial pathogens. Prior to this study, three species of the enterobacterial genus Yersinia that cause invasive human diseases (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica) had been sequenced. However, there were no genomic data on the Yersinia species with more limited virulence potential, frequently found in soil and water environments.

Results

We used high-throughput sequencing-by-synthesis instruments to obtain 25- to 42-fold average redundancy, whole-genome shotgun data from the type strains of eight species: Y. aldovae, Y. bercovieri, Y. frederiksenii, Y. kristensenii, Y. intermedia, Y. mollaretii, Y. rohdei, and Y. ruckeri. The deepest branching species in the genus, Y. ruckeri, causative agent of red mouth disease in fish, has the smallest genome (3.7 Mb), although it shares the same core set of approximately 2,500 genes as the other members of the species, whose genomes range in size from 4.3 to 4.8 Mb. Yersinia genomes had a similar global partition of protein functions, as measured by the distribution of Cluster of Orthologous Groups families. Genome to genome variation in islands with genes encoding functions such as ureases, hydrogeneases and B-12 cofactor metabolite reactions may reflect adaptations to colonizing specific host habitats.

Conclusions

Rapid high-quality draft sequencing was used successfully to compare pathogenic and non-pathogenic members of the Yersinia genus. This work underscores the importance of the acquisition of horizontally transferred genes in the evolution of Y. pestis and points to virulence determinants that have been gained and lost on multiple occasions in the history of the genus.
The role of macrophages in the development and progression of AIDS-related non-Hodgkin lymphoma
Authors: Huysentruyt Leanne C , McGrath Michael S
Published: December 2009

Review of the potential role of macrophage viral reservoirs in AIDS-related lymphoma development and metastasis by focusing on the possibility that HIV creates pathogenic environments.

Despite HAART, patients infected with HIV develop NHL at a significantly higher level than the noninfected population. The primary difference between lymphoma in non-HIV-infected individuals and those with ARL is that ARL is consistently high-grade and metastatic. The emergence of ARL is associated with the presence of macrophage viral reservoirs, similar to what has been observed for HAD. HIV-infected macrophages, as seen by histology and HIV p24 staining, are present in approximately half of ARLs. Macrophage reservoirs recruit additional immune cells, including monocytes/macrophages, through the release of chemoattractants. Additionally, TAM are known to promote tumor progression for most cancer types, including lymphomas. This review will highlight and discuss the role of macrophage viral reservoirs in the development and progression of ARLs and hopefully, shed light on this new and interesting field.
Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor
Authors: Connolly Michael K , Mallen-St. Clair Jon , Bedrosian Andrea S , Malhotra Ashim , Vera Valery , Ibrahim Junaid , Henning Justin , Pachter H Leon , Bar-Sagi Dafna , Frey Alan B , Miller George
Published: December 2009

The expansion of distinct immune suppressive cells in the liver of tumor bearing hosts may bear on the propensity of patients with intra-abdominal cancers to develop liver metastases.

The liver is the most common site of adenocarcinoma metastases, even in patients who initially present with early disease. We postulated that immune-suppressive cells in the liver of tumor-bearing hosts inhibit anti-tumor T cells, thereby accelerating the growth of liver metastases. Using models of early preinvasive pancreatic neoplasia and advanced colorectal cancer, aims of this study were to determine immune phenotype, stimulus for recruitment, inhibitory effects, and tumor-enabling function of immune-suppressive cells in the liver of tumor-bearing hosts. We found that in mice with intra-abdominal malignancies, two distinct CD11b+Gr1+ populations with divergent phenotypic and functional properties accumulate in the liver, becoming the dominant hepatic leukocytes. Their expansion is contingent on tumor expression of KC. These cells are distinct from CD11b+Gr1+ populations in other tissues of tumor-bearing hosts in terms of cellular phenotype and cytokine and chemokine profile. Liver CD11b+Gr1+ cells are highly suppressive of T cell activation, proliferation, and cytotoxicity and induce the development of Tregs. Moreover, liver myeloid-derived suppressor cells accelerate the development of hepatic metastases by inactivation of cytotoxic T cells. These findings may explain the propensity of patients with intra-abdominal cancers to develop liver metastases and suggest a promising target for experimental therapeutics.
Macrophage polarization and HIV-1 infection
Authors: Cassol Edana , Cassetta Luca , Alfano Massimo , Poli Guido
Published: December 2009

Review of the role of human M1 and M2 macrophage polarization in HIV-1 infection.

Polarization of MP into classically activated (M1) and alternatively activated (M2a, M2b, and M2c) macrophages is critical in mediating an effective immune response against invading pathogens. However, several pathogens use these activation pathways to facilitate dissemination and pathogenesis. Viruses generally induce an M1-like phenotype during the acute phase of infection. In addition to promoting the development of Th1 responses and IFN production, M1 macrophages often produce cytokines that drive viral replication and tissue damage. As shown for HIV-1, polarization can also alter macrophage susceptibility to infection. In vitro polarization into M1 cells prevents HIV-1 infection, and M2a polarization inhibits viral replication at a post-integration level. M2a cells also express high levels of C-type lectins that can facilitate macrophage-mediated transmission of HIV-1 to CD4+ T cells. Macrophages are particularly abundant in mucosal membranes and unlike DCs, do not usually migrate to distal tissues. As a result, macrophages are likely to contribute to HIV-1 pathogenesis in mucosal rather than lymphatic tissues. In vivo polarization of MP is likely to span a spectrum of activation phenotypes that may change the permissivity to and alter the outcome of HIV-1 and other viral infections.
A marvellous recovery - extra
Authors: Bewley Thomas
Published: December 2009

In 1955 I was a registrar at Claybury Hospital when a woman aged 52 was transferred from a general hospital, where she had been for several weeks following a stroke after which there were no signs of recovery. She could not speak, did not appear to be aware of her surroundings and needed spoon-feeding and total nursing care. She was therefore admitted directly to a long-stay psychogeriatric ward, without having been seen by a consultant in the normal admission ward. When I examined her I found she was in better physical health than I might have expected and she was free of any signs of pressure sores. Two days after admission she moved her limbs slightly and said ‘Thank you’ to a nurse who was feeding her. On each of the following days there was a steady improvement in her condition. The nurses on this ward, who were not accustomed to seeing such improvements, were surprised by the changes. I encouraged them to help her to sit up, stand up, move to a chair, walk a little with help, walk further without help, until she gradually became able to look after herself. Her speech improved at the same time, an occasional slurred word was followed by clearer sentences and within 3 weeks she was talking normally. She had no idea of what had led to her being in hospital, but accepted the fact that she had been seriously ill. Her family, who visited her daily, were very impressed and delighted by her rapid return to her old self. Five weeks after admission she had few obvious sequelae and went home. Her family thanked me very warmly for my endeavours. They told me that the very best thing that had ever happened to their mother was her transfer from a hospital where nothing could be done to a mental hospital where modern psychiatric treatment brought about cure. I told them that I had done little but that the nurses had been very good in helping to rehabilitate her. ‘No, no,’ they said ‘if it wasn't for you, Dr Bewley, none of this would have happened.’ I think they saw me as the greatest doctor since Paracelsus. In my next 40 years as a psychiatrist I never came across a more grateful family.
A Lover's Quarrel - poems by doctors
Authors: Hanlon Vincent
Published: December 2009

Describe it simply as a lovers' quarrel after which she slashed her wrist and sought medical attention.
White matter microstructural abnormalities in euthymic bipolar disorder
Authors: Macritchie Karine A. N. , Lloyd Adrian J. , Bastin Mark E. , Vasudev Kamini , Gallagher Peter , Eyre Rachel , Marshall Ian , Wardlaw Joanna M. , Ferrier I. Nicol , Moore P. Brian , Young Allan H.
Published: December 2009

Background

Abnormal diffusion parameters are reported in specific brain regions and white matter tracts in bipolar disorder.

Aims

To investigate whether these abnormalities are generalised, and thus evident in large regions of white matter.

Method

Diffusion parameters were measured at several regions in the corpus callosum and in deep/periventricular white matter in 28 currently euthymic patients with bipolar disorder and controls. White matter hyperintensity loads were assessed.

Results

Comparing the whole data-sets using the sign test, in the group with bipolar disorder, mean diffusivity was greater at all 15 sites (P<0.001) and fractional anisotropy was reduced at 13 (P<0.01). The effect of diagnosis was significant for callosal mean diffusivity and fractional anisotropy and for deep/periventricular mean diffusivity (MANCOVA). Comparing individual regions (Mann–Whitney U-test), prefrontal and periventricular mean diffusivity were significantly increased; callosal and occipital fractional anisotropy were significantly reduced. Former substance use and lithium were possible confounding factors. Periventricular white matter hyperintensities were associated with significantly increased periventricular mean diffusivity in individuals with bipolar disorder.

Conclusions

Generalised white matter microstructural abnormalities may exist in bipolar disorder, possibly exacerbated by past substance use and ameliorated by lithium.
Risk of psychological distress following severe obstetric complications in Benin: the role of economics, physical health and spousal abuse
Authors: Fottrell Edward , Kanhonou Lydie , Goufodji Sourou , Béhague Dominique P. , Marshall Tom , Patel Vikram , Filippi Véronique
Published: December 2009

Background

Little is known about the impact of life-threatening obstetric complications (‘near miss’) on women's mental health in low- and middle-income countries.

Aims

To examine the relationships between near miss and postpartum psychological distress in the Republic of Benin.

Method

One-year prospective cohort using epidemiological and ethnographic techniques in a population of women delivering at health facilities.

Results

In total 694 women contributed to the study. Except when associated with perinatal death, near-miss events were not associated with greater risk of psychological distress in the 12 months postpartum compared with uncomplicated childbirth. Much of the direct effect of near miss with perinatal death on increased risk of psychological distress was shown to be mediated through wider consequences of traumatic childbirth.

Conclusions

A live baby protects near-miss women from increased vulnerability by giving a positive element in their lives that helps them cope and reduces their risk of psychological distress. Near-miss women with perinatal death should be targeted early postpartum to prevent or treat the development of depressive symptoms.
Risk factors for suicide in rural south India
Authors: Manoranjitham S. D. , Rajkumar A. P. , Thangadurai P. , Prasad J. , Jayakaran R. , Jacob K. S.
Published: December 2009

Background

The relative contributions of psychosocial stress and psychiatric morbidity to suicide are a subject of debate.

Aims

To determine major risk factors for suicide in rural south India.

Method

We used a matched case–control design and psychological autopsy to assess 100 consecutive suicides and 100 living controls matched for age, gender and neighbourhood.

Results

Thirty-seven (37%) of those who died by suicide had a DSM–III–R psychiatric diagnosis. Alcohol dependence (16%) and adjustment disorders (15%) were the most common categories. The prevalence rates for schizophrenia, major depressive episode and dysthymia were 2% each. Ongoing stress and chronic pain heightened the risk of suicide. Living alone and a break in a steady relationship within the past year were also significantly associated with suicide.

Conclusions

Psychosocial stress and social isolation, rather than psychiatric morbidity, are risk factors for suicide in rural south India.
TENTS guidelines: development of post-disaster psychosocial care guidelines through a Delphi process
Authors: Bisson Jonathan I. , Tavakoly Behrooz , Witteveen Anke B. , Ajdukovic Dean , Jehel Louis , Johansen Venke J. , Nordanger Dag , Garcia Francisco Orengo , Punamaki Raija-Leena , Schnyder Ulrich , Sezgin A. Ufuk , Wittmann Lutz , Olff Miranda
Published: December 2009

Background

How best to plan and provide psychosocial care following disasters remains keenly debated.

Aims

To develop evidence-informed post-disaster psychosocial management guidelines.

Method

A three-round web-based Delphi process was conducted. One hundred and six experts rated the importance of statements generated from existing evidence using a one to nine scale. Participants reassessed their original scores in the light of others' responses in the subsequent rounds.

Results

A total of 80 (72%) of 111 statements achieved consensus for inclusion. The statement ‘all responses should provide access to pharmacological assessment and management’ did not achieve consensus. The final guidelines recommend that every area has a multi-agency psychosocial care planning group, that responses provide general support, access to social, physical and psychological support and that specific mental health interventions are only provided if indicated by a comprehensive assessment. Trauma-focused cognitive–behavioural therapy (CBT) is recommended for acute stress disorder or acute post-traumatic stress disorder, with other treatments with an evidence base for chronic post-traumatic stress disorder being made available if trauma-focused CBT is not tolerated.

Conclusions

The Delphi process allowed a consensus to be achieved in an area where there are limitations to the current evidence.
Validity of a short clinical interview for psychiatric diagnosis: the mini-SCAN
Authors: Nienhuis F. J. , van de Willige G. , Rijnders C. A. Th. , de Jonge P. , Wiersma D.
Published: December 2009

Background

To promote clinical application of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) system a shorter version (the mini-SCAN) was devised. Its psychometric properties were unknown.

Aims

To establish the validity and practical properties of the mini-SCAN.

Method

One hundred and six participants were interviewed twice, once with the SCAN and once with the mini-SCAN. The level of agreement was established for the categories: no disorder, affective disorders, anxiety disorders, non-affective psychotic disorders, affective psychotic disorders.

Results

The mini-SCAN is a valid instrument. Most kappa values were around 0.90. Only for the class of affective psychotic disorders was the agreement moderate. Mean duration of the mini-SCAN interviews was 25 min shorter than the SCAN interviews. Participants and interviewers were generally satisfied with the interview format and questions.

Conclusions

The mini-SCAN can be used as a diagnostic instrument for clinical purposes and for clinical studies when the present episode is the focus of attention.
Non-fatal repetition of self-harm: population-based prospective cohort study in Taiwan
Authors: Chen Vincent C. H. , Tan Happy K. L. , Cheng Andrew T. A. , Chen Chung-Ying , Liao Long-Ren , Stewart Robert , Dewey Michael , Prince Martin
Published: December 2009

Background

Repeated self-harm is relatively common and is linked with an elevated risk of eventual suicide. There has been no study of this involving a large sample from the Far East.

Aims

To estimate the risk over the medium term of non-fatal repetition of self-harm and identify predictive factors in those carrying out self-harm.

Method

A total of 970 individuals who had self-harmed were recruited from a community-based suicide behaviour register system in Nantou, Taiwan from July 2000 to February 2003. Information regarding demography and suicide methods was collected. Individuals were followed-up until December 2005 to examine the risk of repeated self-harm and independent predictive factors.

Results

Ninety cohort members had repeated self-harm during the follow-up period (accounting for 131 repeated self-harm episodes in all). The cumulative risks were 5.7% for the first year, 7.8% for the second year and 9.5% for the fourth year. The risk was highest within the first year after the self-harm event. Independent risk factors included female gender and self-cutting as well as self-poisoning with drugs. Effect of younger age was mediated through the choice of methods.

Conclusions

Individuals with self-harm have a high risk of repetition, especially within the first year. Suicide prevention strategies need to focus on intervening with this population to reduce their repetition.
Risk of developing dementia in people with diabetes and mild cognitive impairment
Authors: Velayudhan Latha , Poppe Michaela , Archer Nicola , Proitsi Petroula , Brown Richard G. , Lovestone Simon
Published: December 2009

Background

Diabetes mellitus is associated with cognitive dysfunction, but it is not clear whether the disorder increases the risk of conversion from mild cognitive impairment to dementia.

Aims

To determine the association between diabetes mellitus and dementia conversion in people with mild cognitive impairment (Peterson's criteria) in a prospective community-based study.

Method

People over 65 years old were approached through primary care practices in south London, UK, and those with mild cognitive impairment (n = 103) were followed up for 4 years. Presence of diabetes was established from self-report and information from general practitioners.

Results

Nineteen participants progressed to dementia, with the predominant diagnosis being probable or possible Alzheimer's disease (in 84%). Only diabetes mellitus was associated with progression to dementia (hazard ratio 2.9, 95% CI 1.1–7.3) after adjustment for sociodemographic factors, APOE4, premorbid IQ and other health conditions.

Conclusions

Diabetes mellitus increases not only the risks of dementia and mild cognitive impairment but also the risk of progression from such impairment to dementia.
Ethnicity and coercion among involuntarily detained psychiatric in-patients
Authors: Bennewith Olive , Amos Tim , Lewis Glyn , Katsakou Christina , Wykes Til , Morriss Richard , Priebe Stefan
Published: December 2009

We assessed whether adult Black and minority ethnic (BME) patients detained for involuntary psychiatric treatment experienced more coercion than similar White patients. We found no evidence of this from patient interviews or from hospital records. The area (mental health trust) where people were treated was strongly associated with both the experience of coercion and the recording of a coercive measure in their records. Regarding charges of institutional racism in psychiatry, this study highlights the importance of investigating the role of area characteristics when assessing the relationship between ethnicity and patient management.
Improving the Efficiency and Efficacy of Controlled Sequential Bifurcation for Simulation Factor Screening
Authors: Wan Hong , Ankenman Bruce E. , Nelson Barry L.
Published: December 2009

Controlled sequential bifurcation (CSB) is a factor-screening method for discrete-event simulations. It combines a multistage hypothesis testing procedure with the original sequential bifurcation procedure to control both the power for detecting important effects at each bifurcation step and the Type I error for each unimportant factor under heterogeneous variance conditions when a main-effects model applies. This paper improves the CSB procedure in two aspects. First, a new fully sequential hypothesis-testing procedure is introduced that greatly improves the efficiency of CSB. Moreover, this paper proposes CSB-X, a more general CSB procedure that has the same error control for screening main effects that CSB does, even when two-factor interactions are present. The performance of the new method is proven and compared with the original CSB procedure.
Integrated Airline Schedule Design and Fleet Assignment: Polyhedral Analysis and Benders' Decomposition Approach
Authors: Sherali Hanif D. , Bae Ki-Hwan , Haouari Mohamed
Published: December 2009

The main airline operations consist of schedule planning, fleet assignment, aircraft routing, and crew scheduling. To improve profitability, we present in this paper an integrated fleet assignment model with schedule planning by simultaneously considering optional flight legs to select along with the assignment of aircraft types to all scheduled legs. In addition, we consider itinerary-based demands for multiple fare classes. A polyhedral analysis is conducted of the proposed mixed-integer programming model to tighten its representation via several classes of valid inequalities. Solution approaches are developed by applying Benders' decomposition method to the resulting lifted model, and computational results are presented using real data obtained from a major U.S. airline to demonstrate the efficacy of the proposed procedures.