bluuebunny/crossref_metadata_2025 huggingface dataset:
Signal transduction inhibitors and antiangiogenic therapies for malignant glioma
Authors: Mellinghoff Ingo K. , Lassman Andrew B. , Wen Patrick Y.
Published: February 2011

Detailed characterization of the cancer genome in a large number of primary human glioblastomas has identified recurrent alterations that result in deregulation of signal transduction pathways and are “druggable” with a growing number of small molecule pharmaceuticals. While many of these compounds have shown clinical activity in other human cancers harboring similar genetic alterations, the clinical experience in glioblastoma has been disappointing thus far with only rare and transient radiographic responses. Our understanding of drug resistance is confounded by the uncertainty of drug delivery across the blood brain barrier and the limited knowledge to what extent the growth of these tumors depends on any particular signaling pathway. This uncertainty is, at least in part, due to shortcomings in the current approach to evaluate signal transduction inhibitors in glioma patients, including drug testing in molecularly unselected patient populations, limited documentation of drug penetration and target inhibition in tumor tissue, and use of radiographic response criteria that may not be optimal for the evaluation of these compounds. © 2011 Wiley‐Liss, Inc.
Schwann cell plasticity after spinal cord injury shown by neural crest lineage tracing
Authors: Nagoshi Narihito , Shibata Shinsuke , Hamanoue Makoto , Mabuchi Yo , Matsuzaki Yumi , Toyama Yoshiaki , Nakamura Masaya , Okano Hideyuki
Published: February 2011

After spinal cord injury (SCI), various cell types are recruited to the lesion site, including Schwann cells, which originate in the neural crest and normally myelinate axons in the peripheral nervous system. Here, we investigated the differentiation states, migration patterns, and roles of neural crest derivatives following SCI, using two transgenic mouse lines carrying neural crest‐specific reporters, P0‐Cre/Floxed‐EGFP and Wnt1‐Cre/Floxed‐EGFP. In these mice, EGFP is expressed only in the neural crest cell lineage. Immunohistochemical analysis revealed that most of the EGFP+ cells that infiltrated the lesion site after SCI were Schwann cells. Seven days after SCI, the P0‐positive, mature Schwann cells residing at the nerve roots had dedifferentiated into P0−/p75+ immature Schwann cells, which proliferated and began migrating into the lesion site. The dedifferentiation of the Schwann cells was corroborated by their expression of phosphorylated c‐Jun, which promotes dedifferentiation and inhibits the expression of myelin‐associated genes in the peripheral nerves. Thereafter, the number of EGFP+/p75+ immature Schwann cells decreased and that of EGFP+/P0+ mature cells increased gradually, indicating that the cells redifferentiated into mature Schwann cells within the lesion site. This study draws on the advantages offered by transgenic mouse lines bearing a genetic cell‐lineage marker and extends previous work by describing the origins and behavior of the neural crest‐derived cells that contribute to endogenous repair after SCI. This process, involving Schwann cell plasticity, is a novel repair mechanism for the lesioned mammalian spinal cord. © 2011 Wiley‐Liss, Inc.
NG2 cells are not a major source of reactive astrocytes after neocortical stab wound injury
Authors: Komitova Mila , Serwanski David R. , Richard Lu Q. , Nishiyama Akiko
Published: February 2011

NG2 cells are an abundant glial cell type in the adult brain. They are distinct from astrocytes, mature oligodendrocytes, and microglia. NG2 cells generate oligodendrocytes and a subpopulation of protoplasmic astrocytes in the ventral forebrain during development. To determine whether NG2 cells generate reactive astrocytes in the lesioned brain, stab wound injury was created in adult NG2creBAC:ZEG double transgenic mice, in which enhanced green fluorescent protein (EGFP) is expressed in NG2 cells and their progeny, and the phenotype of the EGFP+ cells was analyzed at 10 and 30 days post lesion (dpl). The majority (>90%) of the reactive astrocytes surrounding the lesion that expressed glial fibrillary acidic protein (GFAP) lacked EGFP expression, and conversely the majority (>90%) of EGFP+ cells were GFAP‐negative. However, 8% of EGFP+ cells co‐expressed GFAP at 10 dpl. Most of these EGFP+GFAP+ cells were morphologically distinct from hypertrophic reactive astrocytes and exhibited weak GFAP expression. NG2 was detected in a fraction of the EGFP+GFAP+ cells found at 10 dpl. By 30 dpl the number of EGFP+GFAP+ cells had decreased more than four‐fold from 10 dpl. A similar transient appearance of EGFP+GFAP+ cells with simple morphology was observed in NG2creER™:ZEG double transgenic mice in which EGFP expression had been induced in NG2 cells prior to injury. NG2 cell‐specific deletion of the oligodendrocyte lineage transcription factor Olig2 using NG2creER™:Olig2fl/fl:ZEG triple transgenic mice did not increase the number of EGFP+ reactive astrocytes. These findings suggest that NG2 cells are not a major source of reactive astrocytes in the neocortex. © 2011 Wiley‐Liss, Inc.
Effects of aging on 5‐HT2AR binding: a HRRT PET study with and without partial volume corrections
Authors: Uchida Hiroyuki , Chow Tiffany W. , Mamo David C. , Kapur Shitij , Mulsant Benoit H. , Houle Sylvain , Pollock Bruce G. , Graff‐Guerrero Ariel
Published: February 2011

Objective

We explored whether prior findings of reduction in serotonin 2A receptor (5‐HT2AR) binding with age could be replicated and whether high resolution research tomography (HRRT) for positron emission tomography could compensate for partial volume effects in the presence of age‐related brain atrophy, which has been a traditional concern for radioligand PET studies in the elderly.

Methods

We derived 5‐HT2AR nondisplaceable binding potentials (BPND) in frontal, temporal, anterior‐cingulate, insula, caudate and putamen volumes of interest (VOIs) for 28 healthy subjects (mean ± SD age = 43.9 ± 17.0 years, range: 19–78 years) using HRRT. Partial volume correction (PVC) was performed in the VOI analysis.

Results

The 5‐HT2AR BPNDs decreased with age, a relationship best described by an exponential‐decay regression. The BPNDs were found to be consistent before and after PVC, with an intra‐class correlation coefficient of 0.84 and 95% confidence interval = 0.78–0.88.

Conclusions

These new findings update current knowledge, in that the aging process is not always uniform across the life span and suggest that PVC may not be necessary with HRRT in healthy subjects. Copyright © 2011 John Wiley & Sons, Ltd.
Depressive symptoms predict longitudinal change in executive control but not memory
Authors: Royall Donald R. , Palmer Raymond , Chiodo Laura K. , Polk Marsha J.
Published: February 2011

Objective

Depression in non‐demented persons has been identified as a possible risk factor for incident Alzheimer's disease (AD).

Methods

Latent Growth Curve models were developed of baseline depressive symptoms as a predictor of longitudinal changes in cognition. Depressive symptoms were assessed using the 15‐item Geriatric Depression Scale (GDS). Memory was assessed by the California Verbal Learning Task (CVLT). Executive control function (ECF) was assessed by the Executive Interview (EXIT25) and Trail‐Making Test Part B (Trails‐B). Five hundred forty‐seven non‐institutionalized older retirees living in a single comprehensive care retirement community participated.

Results

Depressive symptoms were significantly associated only with the 3‐year rate of decline in psychomotor speed, as measured by Trails A, and ECF, as measured by the EXIT25. Both associations withstood adjustment for age, gender, education, and baseline level of care.

Conclusions

Depressive symptoms are associated with longitudinal decline in cognition. However, this association selectively involves executive control, not memory, and possibly only a subset of ‘executive’ functions. Although depressive symptoms may hasten conversion from mild cognitive impairment (MCI) to dementia, depression‐related conversion is not likely to be mediated by evolution of the AD pathological process. Copyright © 2011 John Wiley & Sons, Ltd.
Overweight and obesity and the utilization of primary care physicians
Authors: Gupta Nabanita Datta , Greve Jane
Published: February 2011

We investigate whether overweight or obese individuals utilize more medical care than normal weight individuals by estimating a finite mixture model which splits the population into frequent and non‐frequent users of primary care physician (GP) services. Based on a survey sample aged 25–60 years from the National Health Interview (NHI) 2000 merged to Danish register data, we compare differences in the impact of being overweight and obese relative to being normal weight on the utilization of GP services. Estimated bodyweight effects vary across latent classes and show that being obese or overweight does not increase the utilization of GP services among infrequent users but does so among frequent users. Obese (and to a lesser extent, overweight) infrequent users are observed 5 years later to substantially increase their health‐care usage as measured by doctor visits, hospitalizations, and number of bed days. Copyright © 2011 John Wiley & Sons, Ltd.
Paneth cell-derived interleukin-17A causes multiorgan dysfunction after hepatic ischemia and reperfusion injury
Authors: Park Sang Won , Kim Mihwa , Brown Kevin M. , D'Agati Vivette D. , Lee Thomas H.
Published: February 2011

Hepatic ischemia and reperfusion (IR) injury is a major clinical problem that leads to frequent extrahepatic complications including intestinal dysfunction and acute kidney injury (AKI). In this study we aimed to determine the mechanisms of hepatic IR-induced extrahepatic organ dysfunction. Mice subjected to 60 minutes of hepatic IR not only developed severe hepatic injury but also developed significant AKI and small intestinal injury. Hepatic IR induced small intestinal Paneth cell degranulation and increased interleukin-17A (IL-17A) levels in portal vein plasma and small intestine. We also detected increased levels of IL-17A messenger RNA (mRNA) and protein in Paneth cells after hepatic IR with laser capture dissection. IL-17A-neutralizing antibody treatment or genetic deletion of either IL-17A or IL-17A receptors significantly protected against hepatic IR-induced acute liver, kidney, and intestinal injury. Leukocyte IL-17A does not contribute to organ injury, as infusion of wildtype splenocytes failed to exacerbate liver and kidney injury in IL-17A-deficient mice after hepatic IR. Depletion of Paneth cell numbers by pharmacological (with dithizone) or genetic intervention (SOX9 flox/flox Villin cre+/− mice) significantly attenuated intestinal, hepatic, and renal injury following liver IR. Finally, depletion of Paneth cell numbers significantly decreased small intestinal IL-17A release and plasma IL-17A levels after liver IR.

Conclusion:

Taken together, the results show that Paneth cell-derived IL-17A plays a critical role in hepatic IR injury and extrahepatic organ dysfunction. Modulation of Paneth cell dysregulation may have therapeutic implications by reducing systemic complications arising from hepatic IR. (Hepatology 2011;)
Public health in Thailand: Emerging focus on non‐communicable diseases
Authors: Kaufman Nicholas D. , Chasombat Sanchai , Tanomsingh Saengchom , Rajataramya Benjaporn , Potempa Kathleen
Published: February 2011

Over the past three decades, the public health landscape in Thailand has shifted remarkably. Currently chronic non‐communicable diseases represent the largest cause of mortality in the Thai population. In light of the current situation, this paper synthesizes what is known about the chronic non‐communicable disease situation in Thailand and analyzes current policy responses. Relevant contextual factors such as socio‐economic transitions, health systems development, and health workforce capacities are also considered. Primary data for this study were collected by a review of policy documents, government statements, and statistics reported by the Thailand Ministry of Public Health. Secondary data were obtained by a thorough review of the existing literature. The paper finds that while current policy responses to chronic non‐communicable diseases in the health sector have focused on improving prevention and control of risk factors, a stronger emphasis on chronic disease treatment and management may be needed in the future. The paper concludes with an exploration of the potential for developing and implementing realistic public health responses to the growing burden of chronic non‐communicable diseases in a Southeast Asian country context by utilizing existing capacities in research, policy, and health workforce development. Copyright © 2011 John Wiley & Sons, Ltd.
Fibroblast growth factor‐2 enhances NK sensitivity of hepatocellular carcinoma cells
Authors: Tsunematsu Hinako , Tatsumi Tomohide , Kohga Keisuke , Yamamoto Masashi , Aketa Hiroshi , Miyagi Takuya , Hosui Atsushi , Hiramatsu Naoki , Kanto Tatsuya , Hayashi Norio , Takehara Tetsuo
Published: February 2011

The roles of fibroblast growth factor‐2 (FGF‐2) in the hepatocellular carcinoma (HCC) development are still controversial. In this study, we investigated the expression of FGF‐2 in chronic hepatitis (CH) type C patients with or without HCC and the immunoregulation of FGF‐2 in NK sensitivity of HCC cells. The FGF‐2 expressions were detected in the liver tissues of patients, but not in normal liver. The serum FGF‐2 levels of the patients with CH, liver cirrhosis (LC) or HCC were significantly higher than those of healthy volunteers. The serum FGF‐2 levels of patients decreased with the progression of chronic liver disease. HCC occurrence of LC patients with high levels of serum FGF‐2 was significantly lower than that with low levels of serum FGF‐2. Proinflammatory cytokines, such as IL‐1β and IL‐6, induced FGF‐2 expressions in HCC cells and normal hepatocytes. FGF‐2 stimulation resulted in increasing the expression of the membrane‐bound major histocompatibility complex class I‐related chain A (MICA), an NK activating molecule, and decreasing that of human leukocyte antigen (HLA) class I, an NK inhibitory molecule, on HCC cells. This did not occur with normal hepatocytes. Adding anti‐FGF receptor‐2 neutralizing antibody resulted in inhibiting the change of MICA and HLA class I expressions on FGF‐2 stimulated HCC cells. FGF‐2 stimulation on HCC cells resulted in increasing NK sensitivity against HCC cells. These findings indicate that FGF‐2 produced by HCC cells or normal hepatocytes of chronic liver disease may play critical roles in eliminating HCC cells by innate immunity.
A reduction of recipient regulatory T cells by cyclophosphamide contributes to an anti‐tumor effect of nonmyeloablative allogeneic stem cell transplantation in mice
Authors: Takeuchi Ario , Eto Masatoshi , Yamada Hisakata , Tatsugami Katsunori , Naito Seiji , Yoshikai Yasunobu
Published: February 2011

We have recently established a unique model system of nonmyeloablative allogeneic stem cell transplantation (SCT) for treatment of murine solid tumors, based on cyclophosphamide‐induced tolerance. An injection of allogeneic donor spleen cells and bone marrow cells (BMC) followed by cyclophosphamide treatment induced a stable mixed chimerism with long lasting tolerance to the allografts. A donor lymphocyte infusion (DLI) in the cyclophosphamide‐induced tolerant mice exerted strong anti‐tumor effects on an MBT‐2 murine bladder tumor, MBT‐2 via their graft versus tumor (GVT) activity. In the present study, we determined whether a cyclophosphamide‐induced reduction of naturally occurring regulatory T cells (Tregs) was associated with the anti‐tumor activity in our nonmyeloablative SCT system. The number of recipient CD4+ CD25+ Foxp3+ Tregs significantly decreased 3 days after an intraperitoneal injection of cyclophosphamide in C3H/HeN mice that had been injected with spleen cells and BMC of donor AKR/J mice, compared with the number of CD4+ CD25+ Foxp3‐ T cells. An adoptive transfer of CD4+ CD25+ T cells from naïve C3H/He x AKR/J F1 mice into recipient mice 1 day after DLI significantly suppressed the expansion and IFN‐γ production of host‐reactive donor CD4+T cells and hampered the MBT‐2 anti‐tumor activity when compared with the transfer of CD4+ CD25‐ T cells. These results indicated that cyclophosphamide‐induced reduction of recipient Tregs is associated with retardation of tumor progression via the expansion of host‐reactive donor T cells and IFN‐γ production after DLI in our nonmyeloablative SCT system.
Controlling the Molecular Assembly of Polyoxometalates from the Nano to the Micron Scale: Molecules to Materials
Authors: Hutin Marie , Long De‐Liang , Cronin Leroy
Published: February 2011

Polyoxometalates (POMs) represent a class of metal‐oxide units based upon oxides of Mo, W, V, and Nb. Such cluster building blocks can also be subsequently self‐organized in complex 1D, 2D, and 3D frameworks leading to functional materials with diverse properties that span size ranges from 1 to 7 nm in terms of the size of the largest molecular units/clusters. However, since the cluster building blocks have great structural flexibility, the design of architectures is non‐trivial due to the sensitive dependence on reaction parameters such as pH, cation type, temperature, templating and linking units, ionic strength, redox agents. Therefore, the ability to control the aggregation or linking of the building blocks to give pre‐defined structure‐types as well as engineering the physical properties — for example, optical, electronic, catalytic activity/reactivity — is a tremendous challenge. In this review we survey our work from the control/design point of view and show how it is becoming possible to control the assembly of POM‐based architectures. We also describe the polyoxometalate‐based molecules‐to‐material transformations that can be seen as an osmotically driven crystal morphogenesis producing tubular architectures. This can be described as a new type of emergent phenomenon.
MicroRNA‐16 targets zyxin and promotes cell motility in human laryngeal carcinoma cell line HEp‐2
Authors: Wu Haidong , Liu Tao , Wang Renjie , Tian Shuang , Liu Min , Li Xin , Tang Hua
Published: February 2011

MicroRNAs are small noncoding RNAs that negatively regulate target mRNAs at the posttranscription level. Here, we show that miR‐16 is upregulated in human laryngeal carcinoma tissues. Inhibition of miR‐16 in HEp‐2 laryngeal cancer cell line could suppress cell migration and enhance cell–cell adhesion. Subsequently, zyxin, whose expression is negatively regulated by miR‐16, is confirmed to be a direct target gene of miR‐16. Furthermore, overexpression of zyxin could also restrain cell movement and enhance cell–cell adhesion. The study of miR‐16 and its target zyxin will shed light on diagnosis and therapy of laryngeal cancer. © 2011 IUBMB IUBMB Life, 63(2): 101–108, 2011
Signaling to the ribosome in cancer—It is more than just mTORC1
Authors: Hannan Katherine M. , Sanij Elaine , Hein Nadine , Hannan Ross D. , Pearson Richard B.
Published: February 2011

It is becoming increasingly clear that dysregulation of protein synthesis contributes to a range of diseases characterized by tissue overgrowth. These include arterial stenosis, cardiac hypertrophy, hamartomas, and cancer. The central hub for the regulation of protein synthesis is the ribosome, where the key signaling pathways downstream of RAS, MYC, and phosphatidylinositol‐3‐kinase (PI3K) converge to confer exquisite, coordinated control of ribosome synthesis and function. Such cooperation ensures strict regulation of protein synthesis rates and cell growth. This review will focus on the role the PI3K/AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway plays in regulating ribosome function during both health and disease, its interaction with the other key growth regulatory pathways activated by RAS and MYC, and the therapeutic potential for targeting this network. © 2011 IUBMB IUBMB Life, 63(2): 79–85, 2011
Gsα activity is reduced in erythrocyte membranes of patients with psedohypoparathyroidism due to epigenetic alterations at the GNAS locus
Authors: Zazo Celia , Thiele Susanne , Martín Cesar , Fernandez-Rebollo Eduardo , Martinez-Indart Lorea , Werner Ralf , Garin Intza , Group Spanish PHP , Hiort Olaf , Perez de Nanclares Guiomar
Published: February 2011

In pseudohypoparathyroidism (PHP), PTH resistance results from impairment of signal transduction of G protein–coupled receptors caused by a deficiency of the Gsα-cAMP signaling cascade due to diminished Gsα activity in maternally imprinted tissues. In PHP-Ia, inactivating mutations of the GNAS gene lead to haploinsufficiency in some tissues with biallelic expression, so in addition to PHP, Albright's hereditary osteodystrophy (AHO) is also present. In PHP-Ib, caused by methylation defects at the GNAS locus, diminished Gsα activity was thought to be limited to maternally imprinted tissues, such as the renal proximal tubule and the thyroid, leading to a lack of AHO. Recently, we demonstrated methylation defects in patients with AHO signs, indicating a connection between epigenetic changes and AHO. Our objective was to determine Gsα activity in erythrocyte membranes in patients with epigenetic defects at the GNAS locus compared to normal controls and patients with inactivating GNAS mutations. Gsα activity and expression, mutation of the GNAS locus, and methylation status were studied in patients with PHP and mild signs of AHO (PHP-Ia: 12; PHP-Ib: 17, of which 8 had some features of AHO). Then, we statistically compared the Gsα activity of the different PHP subtypes. Patients with methylation defects at the GNAS locus show a significant decrease in erythrocyte Gsα activity compared to normal controls (PHP-Ib versus controls, p < .001). This was significantly lower in patients with AHO signs (PHP-Ib + mild-AHO versus PHP-Ib, p < .05). Our research shows that PHP-Ia and PHP-Ib classification is not only overlapped genetically, as reported, but also in terms of Gsα activity. Reduced expression of GNAS due to methylation defects could downregulate Gsα activity in other tissues beyond those described and could also be causative of AHO. © 2011 American Society for Bone and Mineral Research
Bone biopsy findings and correlation with clinical, radiological, and biochemical parameters in children with fractures
Authors: Mäyränpää Mervi K , Tamminen Inari S , Kröger Heikki , Mäkitie Outi
Published: February 2011

In children the diagnosis of osteoporosis is based on fracture history and DXA-derived BMD. Bone biopsy is an invasive but accurate method for studying bone characteristics. In this study we evaluated bone biopsy findings and their correlation with noninvasive measures of bone health. Transiliac bone biopsy was performed on 24 consecutive children (17 boys, median age 12 years, range 6 to 16 years) evaluated for suspected primary osteoporosis. Biopsy findings were compared with normative data and correlated with clinical, radiological, biochemical, and densitometric findings. The patients had sustained altogether 64 nonvertebral fractures (median 2.5) from low- or moderate-energy traumas, and 14 patients (58%) had vertebral fractures. The median lumbar spine BMD Z-score was −1.2 (range −3.1 to +1.0). Hypovitaminosis D was present in 58%. Histomorphometry showed low bone volume in 7 patients and normal bone volume in 17. Bone turnover was high in 7, low in 7, and normal in 10 patients. Histomorphometric findings correlated poorly with fracture history, serum bone turnover markers, and DXA findings. Vitamin D deficiency and low lumbar BMD were associated with high bone turnover in the biopsy. These findings underscore the difficulties in diagnosing pediatric osteoporosis. Bone histomorphometry gives additional information and may be useful when considering bisphosphonate treatment in children with suspected primary osteoporosis. © 2011 American Society for Bone and Mineral Research
Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1
Authors: Zhang Jin , Tu Qisheng , Bonewald Lynda F , He Xi , Stein Gary , Lian Jane , Chen Jake
Published: February 2011

Dickkopf-related protein 1 (DKK1) is essential to maintain skeletal homeostasis as an inhibitor of Wnt signaling and osteogenic differentiation. The purpose of this study was to investigate the molecular mechanisms underlying the developmental stage–specific regulation of the DKK1 protein level. We performed a series of studies including luciferase reporter assays, micro-RNA microarray, site-specific mutations, and gain- and loss-of-function analyses. We found that the DKK1 protein level was regulated via DKK1 3' UTR by miRNA control, which was restricted to osteoblast-lineage cells. As a result of decreased DKK1 protein level by miR-335-5p, Wnt signaling was enhanced, as indicated by elevated GSK-3β phosphorylation and increased β-catenin transcriptional activity. The effects of miR-335-5p were reversed by anti-miR-335-5p treatment, which downregulated endogenous miR-335-5p. In vivo studies showed high expression levels of miR-335-5p in osteoblasts and hypertrophic chondrocytes of mouse embryos, indicating a pivotal role of miR-335-5p in regulating bone development. In conclusion, miR-335-5p activates Wnt signaling and promotes osteogenic differentiation by downregulating DKK1. This cell- and development-specific regulation is essential and mandatory for the initiation and progression of osteogenic differentiation. miR-335-5p proves to be a potential and useful targeting molecule for promoting bone formation and regeneration. © 2011 American Society for Bone and Mineral Research
Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat
Authors: Aghaloo Tara L , Kang Ben , Sung Eric C , Shoff Michael , Ronconi Matthew , Gotcher Jack E , Bezouglaia Olga , Dry Sarah M , Tetradis Sotirios
Published: February 2011

Bisphosphonates (BPs) are medications used commonly to treat primary and metastatic bone cancer, as well as osteoporosis. Although BPs improve bone mineral density, reduce fracture risk, and reduce hypercalcemia of malignancy, some patients develop BP-related osteonecrosis of the jaws (BRONJ). This devastating complication is defined as clinically exposed bone in the maxillofacial region for more than 8 weeks. Despite an increasing number of BRONJ cases since first reported, the disease pathophysiology remains largely unknown. Since published studies suggest a significant role for dental disease in the pathophysiology of BRONJ, we developed a BRONJ animal model where aggressive periodontal disease is induced by ligature placement around the crown of the right maxillary first molar in the presence of vehicle (veh) or zoledronic acid (ZA), a potent BP. Ligature placement induced significant alveolar bone loss, which was attenuated by ZA treatment. Osteonecrosis was observed associated with ligature-induced periodontitis in the ZA-treated group. This was seen as sequestration and extensive periosteal alveolar bone formation on micro–computed tomography (µCT) in the ligated site of BP-treated animals. Histologic examination confirmed these findings, seen as necrotic bone with diffuse loss of osteocytes and empty lacunae, rimming of the necrotic bone by squamous epithelium and inflammation, and exposure to the oral cavity. Importantly, the rat lesions were strikingly similar to those of BRONJ patients. Our data suggest that dental disease and potent BP therapy are sufficient for BRONJ development in the rat. © 2011 American Society for Bone and Mineral Research
Enhanced chondrocyte proliferation and mesenchymal stromal cells chondrogenesis in coculture pellets mediate improved cartilage formation
Authors: Acharya Chitrangada , Adesida Adetola , Zajac Paul , Mumme Marcus , Riesle Jens , Martin Ivan , Barbero Andrea
Published: February 2011

In this study, we aimed at investigating the interactions between primary chondrocytes and mesenchymal stem/stromal cells (MSC) accounting for improved chondrogenesis in coculture systems. Expanded MSC from human bone marrow (BM‐MSC) or adipose tissue (AT‐MSC) were cultured in pellets alone (monoculture) or with primary human chondrocytes from articular (AC) or nasal (NC) cartilage (coculture). In order to determine the reached cell number and phenotype, selected pellets were generated by combining: (i) human BM‐MSC with bovine AC, (ii) BM‐MSC from HLA‐A2+ with AC from HLA‐A2− donors, or (iii) human green fluorescent protein transduced BM‐MSC with AC. Human BM‐MSC and AC were also cultured separately in transwells. Resulting tissues and/or isolated cells were assessed immunohistologically, biochemically, cytofluorimetrically, and by RT‐PCR. Coculture of NC or AC (25%) with BM‐MSC or AT‐MSC (75%) in pellets resulted in up to 1.6‐fold higher glycosaminoglycan content than what would be expected based on the relative percentages of the different cell types. This effect was not observed in the transwell model. BM‐MSC decreased in number (about fivefold) over time and, if cocultured with chondrocytes, increased type II collagen and decreased type X collagen expression. Instead, AC increased in number (4.2‐fold) if cocultured with BM‐MSC and maintained a differentiated phenotype. Chondro‐induction in MSC–chondrocyte coculture is a robust process mediated by two concomitant effects: MSC‐induced chondrocyte proliferation and chondrocyte‐enhanced MSC chondrogenesis. The identified interactions between progenitor and mature cell populations may lead to the efficient use of freshly harvested chondrocytes for ex vivo cartilage engineering or in situ cartilage repair. J. Cell. Physiol. 227: 88–97, 2012. © 2011 Wiley Periodicals, Inc.
Hindered settling of organic pigment dispersions in hydrocarbon liquids
Authors: McKay Robert B.
Published: February 2011

A modified Steinour hindered settling method has been developed for the study of dispersed organic pigment species containing a large proportion of associated immobile liquid. These species are termed flow units with effective volumes and densities different from those of the pigment itself. The effective volume and density are calculated from the final sediment volume fraction after correction (if practicable) by an appropriate packing factor. The mean flow unit diameter (or a size parameter) can then be estimated. The present method has been satisfactorily tested using formalin‐fixed yeast cells as model flow units which can be sized readily by optical microscopy. Data for organic pigment dispersions compare well with their appearance under the optical microscope. Various uses of simplified versions of the present technique in studies of dispersibility and dispersion stability of organic pigments are described and exemplified using mainly copper phthalocyanine pigments in hydrocarbon solvents.
Studies on β‐alkoxypropionitriles as solvents for extractive distillation
Authors: Kuchhal Rakesh K. , Mallik Kanai L.
Published: February 2011

Five solvents of the β‐alkoxypropionitrile series have been studied by gas‐chromatography in order to examine their potential usefulness as solvents for extractive distillation. Four isomers of C4‐olefin and a diene were used as solutes for the determination of activity coefficients at infinite dilution at 30°C. Relative volatilities were calculated for these solvents and compared with those for other commercial solvents used currently. Relative volatilities of seven C4‐hydrocarbons in two solvents were also studied and compared with the existing literature data for β‐methoxypropionitrile containing 5% antisolvent. The present g.c. studies show that besides the well‐studied β‐methoxypropionitrile, the second member of the series, β‐ethoxypropionitrile, also has the potential for use as a selective solvent.
Studies on cyanine dyes: II. Preparation of ferrocene cyanines
Authors: Osman Abdel Megied , Hassan Khairy M. , Khalil Zarif H. , Turin Vlademir D.
Published: February 2011

The condensation of ferrocene aldehyde with quaternary salts of 2‐methyl heterocyclic compounds, in the presence of piperidine as a catalyst, afforded ferrocenyl cyanines. Interaction of ferrocene aldehyde with the non‐quaternised heterocyclic compounds, in the presence of pyridine and sodium ethoxide as a condensing agent, afforded styryl ferrocenes.
A rapid attenuated total reflectance infrared method for tolylene diisocyanate isomer ratio determination
Authors: Corbett J. K.
Published: February 2011

An attenuated total reflectance (ATR) infrared method is described for the determination of the 2,4‐/2,6‐isomer ratio in tolylene diisocyanate. The absorption band intensity ratio at 1076 cm−1 (2,4‐isomer) and 780 cm−1 (2,6‐isomer) is measured.
Purification of carbon dioxide produced during the fermentative production of fodder yeast and ethyl alcohol by saccharomyces cerevisiae
Authors: Abou‐Zeid Abou‐Zeid A. , Shehata Yousef M. , Madi Ahmad G. , El‐Sherbiny Adel , El‐Nagar Ahmad A. , El‐Hafez Kamal Abd
Published: February 2011

The impurities present in carbon dioxide produced during the fermentative production of fodder yeast and ethyl alcohol by Saccharomyces cerevisiae were mainly acetaldehyde and butyraldehyde. 2,4‐DNP reagent was sensitive to these impurities and they were precipitated as hydrazones. The soluble volatile organic compounds were completely removed in washers (I and II). The other impurities present in carbon dioxide were removed by treating the gas with potassium permanganate and activated charcoal to obtain pure gas. The system used in the purification of carbon dioxide in the factory was efficient when washing water was sufficient (2400 litres of running water/h) and the potassium permanganate solution was changed when it was exhausted.
CHALLENGES FOR COMMUNITY‐BASED ADAPTATION: DISCOVERING THE POTENTIAL FOR TRANSFORMATION
Authors: Dodman David , Mitlin Diana
Published: February 2011

This paper considers community‐based adaptation (CBA) to climate change and its relationship to the theory and practice of participatory development. It is argued that CBA needs to recognise the considered experience of participatory development to date, particularly in relation to local involvement in project planning and implementation, as well as acknowledging the specific challenges raised by climate change. Without attention to risks and uncertainty, political structures and institutions, the necessarily multi‐level nature of adaptation policy and programming, and the links between mitigation and adaptation politics and practice, outcomes of CBA interventions are unlikely to support pro‐poor development. Copyright © 2011 John Wiley & Sons, Ltd.
Structural basis of ligand specificity in the human pentraxins, C‐reactive protein and serum amyloid P component
Authors: Mikolajek Halina , Kolstoe Simon E. , Pye Valerie E. , Mangione Palma , Pepys Mark B. , Wood Stephen P.
Published: February 2011

The normal physiological roles of the phylogenetically conserved human plasma proteins C‐reactive protein (CRP) and serum amyloid P component (SAP) are not known. Novel drugs targeting their ligand specificities are in clinical development as both proteins have significant pathophysiological effects, SAP in promoting amyloidosis and CRP in exacerbating ischemic injury. Both proteins bind to phosphoethanolamine and we show here that, under physiological conditions, phosphoethanolamine is bound with higher affinity by human SAP than by human CRP. An explanation is provided by X‐ray crystal structures that show SAP residue Tyr74 allowing additional hydrophobic protein–ligand interactions compared with the equivalent Thr76 of CRP. Docking simulations show many more low energy positions for phosphoethanolamine bound by CRP than by SAP and are consistent with the crystallographic and functional binding results. These fundamental observations on structure–activity relationships will aid the design of improved pentraxin targeting drugs. Copyright © 2011 John Wiley & Sons, Ltd.
Physiologically relevant divalent cations modulate citrate recognition by the McpS chemoreceptor
Authors: Lacal Jesús , García‐Fontana Cristina , Callejo‐García Carla , Ramos Juan‐Luis , Krell Tino
Published: February 2011

The McpS chemoreceptor of Pseudomonas putida KT2440 recognizes six different tricarboxylic acid (TCA) cycle intermediates. However, the magnitude of the chemotactic response towards these compounds differs largely, which has led to distinguish between strong attractants (malate, succinate, fumarate, oxaloacetate) and weak attractants (citrate, isocitrate). Citrate is abundantly present in plant tissues and root exudates and can serve as the only carbon source for growth. Citrate is known to form complexes with divalent cations which are also abundantly present in natural habitats of this bacterium. We have used isothermal titration calorimetry to study the formation of citrate–metal ion complexes. In all cases binding was entropy driven but significant differences in affinity were observed ranging from KD = 157 µM (for Mg2+) to 3 µM (for Ni2+). Complex formation occurred over a range of pH and ionic strength. The ligand binding domain of McpS (McpS‐LBD) was found to bind free citrate, but not complexes with physiologically relevant Mg2+ and Ca2+. In contrast, complexes with divalent cations which are present as trace elements (Co2+, Cd2+ and Ni2+) were recognized by McpS‐LBD. This discrimination differs from other citrate sensing proteins. These results are discussed in the context of the three dimensional structure of free citrate and its complex with Mg2+. Chemotaxis assays using P. putida revealed that taxis towards the strong attractant malate is strongly reduced in the presence of free citrate. However, this reduction is much less important in the presence of citrate–Mg2+ complexes. The physiological relevance of these findings is discussed. Copyright © 2011 John Wiley & Sons, Ltd.
Cyclic CINE‐balanced steady‐state free precession image intensity variations: Implications for the detection of myocardial edema
Authors: Goldfarb James W. , McLaughlin Jeanette , Gray Carol A. , Han Jing
Published: February 2011

Purpose

To evaluate the dependence of CINE‐balanced steady‐state free precession (bSSFP) image intensities on spatial location, cardiac phase, and disease state.

Materials and Methods

Eight subjects with recent myocardial infarctions and eight age‐ and sex‐matched normal volunteers were studied using CINE‐bSSFP imaging to describe cyclic image intensity variations as a function of the cardiac cycle and to optimize and assess the ability of CINE‐bSSFP imaging to depict myocardial edema. Signal intensities of the left ventricular (LV) bloodpool and myocardium were measured using region‐of‐interest analysis across the cardiac cycle. The magnitude and time course of the cyclic variations were evaluated. Mixed‐model analysis of variance was used to examine the influence of physical location, cardiac phase, and presence of myocardial infarction.

Results

The LV bloodpool and myocardial CINE‐bSSFP signal intensities varied significantly with spatial location, cardiac phase, and disease (P < 0.001). Cardiac phase had a significant effect on the signal intensities after adjustments for spatial location. The LV bloodpool signal decreased slowly during systole and rose sharply during LV filling. There were two distinct myocardial intensity peaks, one occurring at peak systole and the other at the end of the LV rapid inflow phase. Myocardial edema was seen as a hyperintense region. Image contrast with adjacent myocardium was the greatest at the end of systole.

Conclusion

Detection of myocardial edema using the conventional CINE‐bSSFP technique is feasible, but is complicated by normal cyclic changes in myocardial image intensities during the cardiac cycle. J. Magn. Reson. Imaging 2011;33:573–581. © 2011 Wiley‐Liss, Inc.
In vitro and in vivo comparison of wrist MR imaging at 3.0 and 7.0 tesla using a gradient echo sequence and identical eight‐channel coil array designs
Authors: Nordmeyer‐Massner Jurek A. , Wyss Michael , Andreisek Gustav , Pruessmann Klaas P. , Hodler Juerg
Published: February 2011

Purpose

To evaluate in vivo MR imaging of the wrist at 3.0 Tesla (T) and 7.0T quantitatively and qualitatively.

Materials and Methods

To enable unbiased signal‐to‐noise ratio (SNR) comparisons, geometrically identical eight‐channel receiver arrays were used at both field strengths. First, in vitro images of a phantom bottle were acquired at 3.0T and 7.0T to obtain an estimate of the maximum SNR gain that can be expected. MR images of the dominant wrist of 10 healthy volunteers were acquired at both field strengths. All measurements were done using the same sequence parameters. Quantitative SNR maps were calculated on a pixel‐by‐pixel basis and analyzed in several regions‐of‐interest. Furthermore, the images were qualitatively evaluated by two independent radiologists.

Results

The quantitative analysis showed SNR increases of up to 100% at 7.0T compared with 3.0T, with considerable variation between different anatomical structures. The qualitative analysis revealed no significant difference in the visualization of anatomical structures comparing 3.0T and 7.0T MR images (P>0.05).

Conclusion

The presented results establish the SNR benefits of the transition from 3.0T to 7.0T for wrist imaging without bias by different array designs and based on exact, algebraic SNR quantification. The observed SNR increase nearly reaches expected values but varies greatly between different tissues. It does not necessarily improve the visibility of anatomic structures but adds valuable latitude for sequence optimization. J. Magn. Reson. Imaging 2011;33:661–667. © 2011 Wiley‐Liss, Inc.
Signal‐to‐noise ratio enhancement of intermolecular double‐quantum coherence MR spectroscopy in inhomogeneous fields with phased array coils on a 3 tesla whole‐body scanner
Authors: Lin Yanqin , Chen Zhong , Zhong Jianhui
Published: February 2011

Purpose

To improve signal‐to‐noise ratio (SNR) of intermolecular double‐quantum coherence (iDQC) MRS on a 3 Tesla (T) whole‐body scanner.

Materials and Methods

A 32‐channel phased array coil was used to acquire iDQC signal of a MRS phantom in the presence of large field inhomogeneity. The obtained individual spectra from the array elements were combined together in the time domain using a multichannel nonparametric singular value decomposition algorithm. The results were compared quantitatively with those acquired with a circularly polarized (CP) head coil.

Results

The achieved gain in SNR ranges from 1.63 to 2.10 relative to the CP coil, mainly depending on the relative position between the surface of the phased array coil and the voxel of acquisition.

Conclusion

SNR enhancement of iDQC MRS in inhomogeneous fields on a 3T whole‐body scanner is feasible with phased array coils. This can facilitate iDQC applications of high‐resolution in vivo spectroscopy in the presence of field inhomogeneity for potential disease diagnosis in humans. J. Magn. Reson. Imaging 2011;33:698–703. © 2011 Wiley‐Liss, Inc.
Cervical muscle area measurements in acute whiplash patients and controls
Authors: Ulbrich Erika J. , Anderson Suzanne E. , Busato Andre , Abderhalden Susanne , Boesch Chris , Zimmermann Heinz , Heini Paul , Hodler Juerg , Sturzenegger Matthias
Published: February 2011

Purpose

To quantitatively compare the muscle cross‐sectional areas (CSAs) of the cervical muscles in symptomatic acute whiplash patients versus healthy controls. We hypothesized, that symptomatic whiplash patients have smaller cervical muscle CSAs than matched controls and that smaller cervical muscle CSAs in women might explain that women more frequently are symptomatic after whiplash injury than men.

Materials and Methods

Prospective controlled study. Thirty‐eight consecutive acute whiplash patients were examined within 48 h after a motor vehicle accident and 38 healthy age‐ and sex‐matched controls, each half female, half male, were examined with the same protocol. MRI CSA measurements were performed of the deep and total cervical extensor muscles as well as the sternocleidomastoid muscles using transversal STIR (Short T1 Inversion Recovery) sequences on level C2, C4, and C5 by two blinded raters. Clinical symptoms were assessed with patient questionnaires (EuroQuol 5D, Specific Whiplash Questionnaire, head‐ and neck pain intensity [VAS]).

Results

Agreement of measurements between the two raters was high (intraclass correlation 0.52 to 0.85 for the different levels). No significant difference in age and body mass index were seen between patients and controls and the distribution of genders across groups was identical. There were no significant differences between patients and controls for all CSAs. Women had consistently smaller CSAs than men. The CSAs showed no significant correlation with the pain intensity of neck pain and headache but a consistent tendency of less neck pain and more headache with greater CSAs.

Conclusion

This small study provides no evidence that subjects with smaller CSAs of cervical extensor muscles have a higher risk in developing symptoms after a whiplash injury and confirms smaller CSA in women. J. Magn. Reson. Imaging 2011;33:668–675. © 2011 Wiley‐Liss, Inc.
Analysis of multiple sclerosis lesions using a fusion of 3.0 T FLAIR and 7.0 T SWI phase: FLAIR SWI
Authors: Grabner Günther , Dal‐Bianco Assunta , Schernthaner Melanie , Vass Karl , Lassmann Hans , Trattnig Siegfried
Published: February 2011

Purpose

To improve multiple sclerosis (MS) research by introducing a new type of contrast, namely, the combination of fluid‐attenuated inversion recovery (FLAIR) data acquired at 3.0 T and 7.0 T susceptibility‐weighted imaging (SWI) phase data. The approach of this new contrast is whole‐brain coverage with 3.0 T‐FLAIR data for lesion detection—currently limited at 7.0 T due to specific absorption rate (SAR) limits—overlaid with high‐resolution, small vessel, and iron‐related 7.0 T SWI contrast. Lesion analysis in terms of penetrating veins and local iron depositions were performed.

Materials and Methods

Data from 10 MS patients were acquired at 3.0 T and at 7.0 T. FLAIR data, acquired at 3.0 T, were registered to 7.0 T SWI phase data and SWI image processing was performed using 3.0 T FLAIR data instead of SWI magnitude data.

Results

A total of 299 MS plaques were detected in eight MS patients. Penetrating veins were found in 75 MS plaques, iron depositions in 48 MS plaques, and veins accompanied with iron depositions in 44 MS plaques.

Conclusion

FLAIR‐SWI provides radiologically known, hyperintense definition of MS lesions overlaid with high‐resolution visualization of iron deposits and venous blood vessels and offers new insights into MS lesions. J. Magn. Reson. Imaging 2011;33:543–549. © 2011 Wiley‐Liss, Inc.
Chondrocyte gene expression is affected by very small iron oxide particles‐labeling in long‐term in vitro MRI tracking
Authors: Foldager Casper Bindzus , Pedersen Michael , Ringgaard Steffen , Bünger Cody , Lind Martin
Published: February 2011

Purpose:

To investigate the effect and dose response of very small iron oxide particles (VSOP) labeling of human chondrocytes for long‐term in vitro MRI tracking.

Materials and Methods:

Chondrocytes were isolated from cartilage biopsies from four patients. The cells for the dose–response study were labeled with 25, 50, or 100 μg/mL VSOP. Quantitative gene expression and cellular proliferation were compared with unlabeled controls at day 1, 3, and 7. The cells suited for MRI tracking were labeled with 50 μg/mL VSOP and embedded in alginate beads, followed by MRI (using T2‐weighted sequences) at day 0, 1, 3, 7, 14, 21, 28, and histology was performed at each time‐point.

Results:

Histology revealed that VSOP particles were intracellularly confined at all time‐points, whereas no extracellular VSOPs were observed. A mean reduction in T2‐value of 25.1 ms (±SD 3.5 ms) was found on T2‐maps. The chondrocyte‐specific genes aggrecan, collagen type 2, and sox9 were all affected by labeling, the two latter in a dose‐dependent manner. VSOPs had no effect on proliferation.

Conclusion:

VSOP labeling of chondrocytes affected gene expression but not proliferation. The labeled chondrocytes could be recognized by MRI for 4 weeks without significant changes in the T2 relaxation time. J. Magn. Reson. Imaging 2011;33:724–730. © 2011 Wiley‐Liss, Inc.