bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoadsorption therapy in patients with multiple sclerosis with steroid-refractory optical neuritis
Authors: Koziolek Michael J , Tampe Desiree , Bähr Matthias , Dihazi Hassan , Jung Klaus , Fitzner Dirk , Klingel Reinhard , Müller Gerhard A , Kitze Bernd 
Published: April 2012

Abstract

Background
In multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended. Immunoadsorption (IA) is regarded as an alternative therapy, but its efficacy and putative mechanism of action still needs to be established.

Methods
We prospectively treated 11 patients with multiple sclerosis who had optical neuritis and fulfilled the indications for apheresis therapy (Trial registration DE/CA25/00007080-00). In total, five IA treatments were performed using tryptophan-IA. Clinical activity (visual acuity, Expanded Disability Status Scale, Incapacity Status Scale), laboratory values and visual evoked potentials were measured before, during and after IA, with a follow-up of six months. Moreover, proteomic analyses were performed to analyze column-bound proteins as well as corresponding changes in patients’ sera.

Results
After the third IA, we detected an improvement of vision in eight of eleven patients, whom we termed responders. Amongst these, the mean visual acuity improved from 0.15 ± 0.12 at baseline to 0.47 ± 0.32 after the third IA (P = 0.0252) up to 0.89 ± 0.15 (P < 0.0001) at day 180 ± 10 after IA. Soluble interleukin-2 receptor decreased in responders (P = 0.03), whereas in non-responders it did not. Proteomic analyses of proteins adsorbed to IA columns revealed that several significant immunological proteins as well as central nervous system protein fragments, including myelin basic protein, had been removed by IA.

Conclusions
IA was effective in the treatment of corticosteroid-refractory optic neuritis. IA influenced the humoral immune response. Strikingly, however, we found strong evidence that demyelination products and immunological mediators were also cleared from plasma by IA.
Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function
Authors: Meuwissen Pieter J , Stolp Bettina , Iannucci Veronica , Vermeire Jolien , Naessens Evelien , Saksela Kalle , Geyer Matthias , Vanham Guido , Arien Kevin K , Fackler Oliver T , Verhasselt Bruno 
Published: April 2012

Abstract

Background
The Nef protein of HIV facilitates virus replication and disease progression in infected patients. This role as pathogenesis factor depends on several genetically separable Nef functions that are mediated by interactions of highly conserved protein-protein interaction motifs with different host cell proteins. By studying the functionality of a series of nef alleles from clinical isolates, we identified a dysfunctional HIV group O Nef in which a highly conserved valine-glycine-phenylalanine (VGF) region, which links a preceding acidic cluster with the following proline-rich motif into an amphipathic surface was deleted. In this study, we aimed to study the functional importance of this VGF region.

Results
The dysfunctional HIV group O8 nef allele was restored to the consensus sequence, and mutants of canonical (NL4.3, NA-7, SF2) and non-canonical (B2 and C1422) HIV-1 group M nef alleles were generated in which the amino acids of the VGF region were changed into alanines (VGF→AAA) and tested for their capacity to interfere with surface receptor trafficking, signal transduction and enhancement of viral replication and infectivity. We found the VGF motif, and each individual amino acid of this motif, to be critical for downregulation of MHC-I and CXCR4. Moreover, Nef’s association with the cellular p21-activated kinase 2 (PAK2), the resulting deregulation of cofilin and inhibition of host cell actin remodeling, and targeting of Lck kinase to the trans-golgi-network (TGN) were affected as well. Of particular interest, VGF integrity was essential for Nef-mediated enhancement of HIV virion infectivity and HIV replication in peripheral blood lymphocytes. For targeting of Lck kinase to the TGN and viral infectivity, especially the phenylalanine of the triplet was essential. At the molecular level, the VGF motif was required for the physical interaction of the adjacent proline-rich motif with Hck.

Conclusion
Based on these findings, we propose that this highly conserved three amino acid VGF motif together with the acidic cluster and the proline-rich motif form a previously unrecognized amphipathic surface on Nef. This surface appears to be essential for the majority of Nef functions and thus represents a prime target for the pharmacological inhibition of Nef.
Distinct Degree of Radiculopathy at Different Levels of Peripheral Nerve Injury
Authors: Takiguchi Noboru , Yoshida Munehito , Taniguchi Wataru , Hashizume Hiroshi , Yamada Hiroshi , Miyazaki Nobuyuki , Nishio Naoko , Nakatsuka Terumasa 
Published: April 2012

Background: Lumbar radiculopathy is a common clinical problem, characterized by dorsal root ganglion (DRG) injury and neural hyperactivity causing intense pain. However, the mechanisms involved in DRG injury have not been fully elucidated. Furthermore, little is known about the degree of radiculopathy at the various levels of nerve injury. The purpose of this study is to compare the degree of radiculopathy injury at the DRG and radiculopathy injury proximal or distal to the DRG. Results: The lumbar radiculopathy rat model was created by ligating the L5 nerve root 2 mm proximal to the DRG or 2 mm distal to the DRG with 6.0 silk. We examined the degree of the radiculopathy using different points of mechanical sensitivity, immunohistochemistry and in vivo patch-clamp recordings, 7 days after surgery. The rats injured distal to the DRG were more sensitive than those rats injured proximal to the DRG in the behavioral study. The number of activated microglia in laminas I–II of the L5 segmental level was significantly increased in rats injured distal to the DRG when compared with rats injured proximal to the DRG. The amplitudes and frequencies of EPSC in the rats injured distal to the DRG were higher than those injured proximal to the DRG. The results indicated that there is a different degree of radiculopathy at the distal level of nerve injury. Conclusions: Our study examined the degree of radiculopathy at different levels of nerve injury. Severe radiculopathy occurred in rats injured distal to the DRG when compared with rats injured proximal to the DRG. This finding helps to correctly diagnose a radiculopathy.
Network Dynamics in Nociceptive Pathways Assessed by the Neuronal Avalanche Model
Authors: Wu José Jiun-Shian , Shih Hsi-Chien , Yen Chen-Tung , Shyu Bai-Chuang 
Published: April 2012

Background: Traditional electroencephalography provides a critical assessment of pain responses. The perception of pain, however, may involve a series of signal transmission pathways in higher cortical function. Recent studies have shown that a mathematical method, the neuronal avalanche model, may be applied to evaluate higher-order network dynamics. The neuronal avalanche is a cascade of neuronal activity, the size distribution of which can be approximated by a power law relationship manifested by the slope of a straight line (i.e., the α value). We investigated whether the neuronal avalanche could be a useful index for nociceptive assessment. Findings: Neuronal activity was recorded with a 4 × 8 multichannel electrode array in the primary somatosensory cortex (S1) and anterior cingulate cortex (ACC). Under light anesthesia, peripheral pinch stimulation increased the slope of the α value in both the ACC and S1, whereas brush stimulation increased the α value only in the S1. The increase in α values was blocked in both regions under deep anesthesia. The increase in α values in the ACC induced by peripheral pinch stimulation was blocked by medial thalamic lesion, but the increase in α values in the S1 induced by brush and pinch stimulation was not affected. Conclusions: The neuronal avalanche model shows a critical state in the cortical network for noxious-related signal processing. The α value may provide an index of brain network activity that distinguishes the responses to somatic stimuli from the control state. These network dynamics may be valuable for the evaluation of acute nociceptive processes and may be applied to chronic pathological pain conditions.
Associations between a neurophysiological marker of central cholinergic activity and cognitive functions in young and older adults
Authors: Young-Bernier Marielle , Kamil Yael , Tremblay François , Davidson Patrick S R 
Published: April 2012

AbstractBackgroundThe deterioration of the central cholinergic system in aging is hypothesized to underlie declines in several cognitive domains, including memory and executive functions. However, there is surprisingly little direct evidence regarding acetylcholine’s specific role(s) in normal human cognitive aging.MethodsWe used short-latency afferent inhibition (SAI) with transcranial magnetic stimulation (TMS) as a putative marker of cholinergic activity in vivo in young (n = 24) and older adults (n = 31).ResultsWe found a significant age difference in SAI, concordant with other evidence of cholinergic decline in normal aging. We also found clear age differences on several of the memory and one of the executive function measures. Individual differences in SAI levels predicted memory but not executive functions.ConclusionIndividual differences in SAI levels were better predictors of memory than executive functions. We discuss cases in which the relations between SAI and cognition might be even stronger, and refer to other age-related biological changes that may interact with cholinergic activity in cognitive aging.
Ubiquitous presence of piscidin-1 in Atlantic cod as evidenced by immunolocalisation
Authors: Ruangsri Jareeporn , Fernandes Jorge M O , Rombout Jan H W M , Brinchmann Monica F , Kiron Viswanath 
Published: April 2012

Abstract

Background
Antimicrobial peptides (AMPs), the natural antibiotics bestowed upon all forms of life, consist of small molecular weight proteins with a broad spectrum antimicrobial activity against a variety of pathogenic microorganisms. Piscidins are one of the AMP families that are imperative for the innate defence mechanisms of teleosts. Atlantic cod, a basal fish belonging to the superorder Paracanthopterygii also possesses multiple piscidin peptides. Two piscidin paralogues (pis1 and pis2) and a novel alternative splice variant of pis2 of this fish were previously described by us. To shed light on other potent roles of these molecules, now we have mapped the distribution of piscidin 1 (Pis1), in different tissues and organs of cod through immunohistochemistry (IHC) employing an affinity purified polyclonal antibody specific to Pis1.

Results
Various cell types and tissues of Atlantic cod including those from the immune organs of naïve fish are armed with Pis1 peptide. Different types of the blood leucocytes and phagocytic cells among the leucocytes examined gave a relatively strong indication of Pis1 immunopositivity. In addition, other cell types such as hematopoietic cells, epithelial cells and multi-granular cells located in the mucosal and hematopoietic tissues were also Pis1-immunoreactive. More interestingly, chondrocytes appear to produce Pis1 and this is the first report on the presence of an AMP in cartilage tissue of fish. Furthermore, Pis1 immunopositivity was detected in other tissues and organs of naïve fish including neural tissues, exocrine and endocrine glands, compound gland cells, excretory kidney, intestinal and respiratory epithelial cells, swim bladder, skin and hypodermis layer, myosepta, liver, heart, eye and oocytes.

Conclusions
Pis1 peptide is produced by various cell types located in different tissues and organs of Atlantic cod. It is present in all immune-related organs of naïve fish and the elevated peptide expression following phagocytosis strongly suggest their involvement in innate defence. Further, its widespread occurrence in non-immune tissues and organs of apparently healthy fish implies that piscidin may have other functions in addition to its role as an immune effector molecule.
Anaemia among adults in Kassala, Eastern Sudan
Authors: Abdallah Tajeldin M , Adam Ishag , Abdelhadi Mutaz A , Siddig Mohammed F , Ali AbdelAziem A 
Published: April 2012

Abstract

Background
The increased heterogeneity in the distribution of social and biological risk factors makes the epidemiology of anaemia a real challenge. A cross-sectional study was conducted at Kassala, Eastern Sudan during the period of January — March 2011 to investigate the prevalence and predictors of anaemia among adults (> 15 years old).

Findings
Out of 646, 234 (36.2%) adults had anaemia; 68 (10.5%); 129 (20.0%) and 37 (5.7%) had mild, moderate and severe anaemia, respectively. In logistic regression analyses, age (OR = 1.0, CI = 0.9–1, P = 0.7), rural vs. urban residency (OR = 0.9, CI = 0.7–1.3, P = 0.9), female vs. male gender (OR = 0.8, CI = 0.6–1.1, P = 0.3), educational level ≥ secondary level vs. < secondary level (OR = 1.0, CI = 0.6–1.6, P = 0.8) and Hudandawa vs. non-Hudandawa ethnicity (OR = 0.8, CI = 0.6–1, P = 0.1) were not associated with anaemia.

Conclusion
There was a high prevalence of anaemia in this setting, anaemia affected adults regardless to their age, sex and educational level. Therefore, anaemia is needed to be screened for routinely and supplements have to be employed in this setting.
Interactions of extracts from selected chewing stick sources with Aggregatibacter actinomycetemcomitans
Authors: Kwamin Francis , Gref Rolf , Haubek Dorte , Johansson Anders 
Published: April 2012

Abstract

Background

Aggregatibacter actinomycetemcomitans produces a leukotoxin that activates a pro-inflammatory death of human monocytes/macrophages. A specific clone of this bacterium (JP2) has a 530-base pair deletion in the leukotoxin promoter gene and significantly enhanced expression of leukotoxin. This specific clone of A. actinomycetemcomitans is common in some African populations and has a strong association with periodontal attachment loss in adolescents in these populations. Chewing sticks of plant origin are commonly used as oral hygiene tool in Africa, but their role as a therapeutic agent in periodontal disease is poorly investigated.

Results
Ethanol extracts were made from 7 common plants used as chewing sticks in West-Africa. None of the tested extracts inhibited growth of A. actinomycetemcomitans. However, extracts from Psidium guajava (Guava) completely neutralized the cell death and pro-inflammatory response of human leukocytes induced by the leukotoxin. None of the six other tested chewing stick extracts showed this effect.

Conclusions
The discovery that extracts from Guava efficiently neutralizes A. actinomycetemcomitans leukotoxicity might lead to novel therapeutic agents and strategies for prevention and treatment of aggressive forms of periodontitis induced by infections with the highly leukotoxic JP2 clone of this bacterium.
Differential Expression of RBM5, EGFR and KRAS mRNA and protein in non-small cell lung cancer tissues
Authors: Liang Hong , Zhang Jie , Shao Chen , Zhao Lijing , Xu Wei , Sutherland Leslie C , Wang Ke 
Published: April 2012

Abstract

Background
RNA binding motif 5 (RBM5) is a tumor suppressor gene that modulates apoptosis through the regulation of alternative splicing of apoptosis-related genes. This study aimed to detect RBM5 expression in non-small cell lung cancer (NSCLC) and to associate RBM5 expression with clinicopathological data from NSCLC patients and EGFR and KRAS expression to better understand the potential role of RBM5 in NSCLC.

Method
Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to detect expression of mRNA and protein, respectively, of RBM5, EGFR and KRAS in 120 paired non-tumor and tumor samples of NSCLC.

Results
The data showed that expression of RBM5 mRNA and protein was significantly reduced in NSCLC compared to normal tissues, whereas expression of both EGFR and KRAS genes was increased in NSCLC compared to normal tissues. Furthermore, the reduced RBM5 protein expression correlated with smoking status, tumor stage and lymph node metastasis of NSCLC, while overexpression of EGFR and KRAS proteins correlated with tumor stage and lymph node metastasis of NSCLC. Overexpression of KRAS protein was more frequent in smokers with NSCLC. In addition, expression of RBM5 mRNA and protein was negatively correlated with expression of EGFR and KRAS mRNA and protein in NSCLC tissues.

Conclusion
This study suggests further evaluation of RBM5 expression is warranted for use of RBM5 as a biomarker for NSCLC patients.
Short and long terms healing of the experimentally transverse sectioned tendon in rabbits
Authors: Oryan Ahmad , Moshiri Ali , Meimandi-Parizi Abdul-Hamid 
Published: April 2012

Abstract

Background
The incidences of tendon injuries in certain sections of human or animal populations such as athletes are high, but every human or animal, regardless of age or level of activity experiences some degree of tendon injury. In spite of the various investigations of injuries and treatment, comprehensive studies dealing with the histological, ultrastructural and biomechanical aspects of healing of load-bearing tendons are rare. This study was designed to compare the outcome of healing of the transverse sectioned superficial digital flexor tendon (SDFT) after 28 and 84 days post injury (DPI) in rabbits.

Methods
Forty white New Zealand mature female rabbits were randomly divided into two equal groups of 28 and 84 DPI After tenotomy and surgical repair of the left SDFT, the injured legs were casted for 14 days. The weight of the animals, tendon diameter, and clinical, radiographic and ultrasonographic evaluations were conducted at weekly intervals. The animals were euthanized on 28 and 84 DPI and the tendons were evaluated for histopathological, ultrastructural, biomechanical and percentage dry weight parameters.

Results
Although the clinical, ultrastructural, morphological and biomechanical properties of the injured tendons on day 84 showed a significant improvement compared to those of the 28 DPI, these parameters were still significantly inferior to their normal contra-lateral tendons.

Conclusions
This study showed that tendon healing is very slow and at 84 days post-injury the morphological and biomechanical parameters were still inferior to the normal tendons and many collagen fibrils still had the same diameter as those seen at 28 DPI.
Nocardia globerula NHB-2 nitrilase catalysed biotransformation of 4-cyanopyridine to isonicotinic acid
Authors: Sharma Nitya Nand , Sharma Monica , Bhalla Tek Chand 
Published: April 2012

Abstract
Isonicotinic acid (INA) is an important pyridine derivative used in the manufacture of isoniazid (antituberculosatic drug) and other pharmaceutically important drugs. Nitrilase catalysed processes for the synthesis of pharmaceutically important acids from their corresponding nitriles are promising alternative over the cumbersome, hazardous, and energy demanding chemical processes. Nitrilase of Nocardia globerula NHB-2 (NitNHB2) is expressed in presence of isobutyronitrile in the growth medium (1.0% glucose, 0.5% peptone, 0.3% beef extract, and 0.1 % yeast extract, pH 7.5). NitNHB2 hydrolyses 4-cyanopyridine (4-CP) to INA without accumulation of isonicotinamide, which is common in the reaction catalysed via fungal nitrilases. The NitNHB2 suffers from substrate inhibition effect and hydrolysing activity up to 250 mM 4-CP was recorded. Complete conversion of 200 mM 4-CP to INA was achieved in 40 min using resting cell concentration corresponding to 10 U mL-1 nitrilase activity in the reaction. Substrate inhibition effect in the fed batch reaction (200 mM substrate feed/40min) led to formation of only 729 mM INA. In a fed batch reaction (100 mM 4-CP/20min), substrate inhibition effect was encountered after 7th feed and a total of 958 mM INA was produced in 400 min. The fed batch reaction scaled up to 1 L and 100% hydrolysis of 700 mM of 4-CP to INA at 35°C achieved in 140 min. The rate of INA production was 21.1 g h-1 mgDCW
-1. This is the fastest biotransformation process ever reported for INA production with time and space productivity of 36 g L-1 h-1 using a bacterial nitrilase.
Reduction of low-density lipoprotein receptor-related protein (LRP1) in hippocampal neurons does not proportionately reduce, or otherwise alter, amyloid deposition in APPswe/PS1dE9 transgenic mice
Authors: Xu Guilian , Green Cameron C , Fromholt Susan E , Borchelt David R 
Published: April 2012

Abstract
Introduction
The low-density lipoprotein receptor-related protein (LRP1) and its family members have been implicated in the pathogenesis of Alzheimer's disease. Multiple susceptibility factors converge to metabolic pathways that involve LRP1, including modulation of the processing of amyloid precursor protein (APP) and the clearance of Aβ peptide.

Methods
We used the Cre-lox system to lower LRP1 levels in hippocampal neurons of mice that develop Alzheimer-type amyloid by crosses between mice that express Cre recombinase under the transcriptional control of the GFAP promoter, mice that harbor loxp sites in the LRP1 gene, and the APPswe/PS1dE9 transgenic model. We compared amyloid plaque numbers in APPswe/PS1dE9 mice lacking LRP1 expression in hippocampus (n = 13) to mice with normal levels of LRP1 (n = 12). Student t-test was used to test whether there were significant differences in plaque numbers and amyloid levels between the groups. A regression model was used to fit two regression lines for these groups, and to compare the rates of Aβ accumulation.

Results
Immunohistochemical analyses demonstrated efficient elimination of LRP1 expression in the CA fields and dentate gyrus of the hippocampus. Within hippocampus, we observed no effect on the severity of amyloid deposition, the rate of Aβ40/42 accumulation, or the architecture of amyloid plaques when LRP1 levels were reduced.

Conclusions
Expression of LRP1 by neurons in proximity to senile amyloid plaques does not appear to play a major role in modulating the formation of these proximal deposits or in the appearance of the associated neuritic pathology.