tbuckley/cabot-search huggingface dataset:
Knee arthroscopy and exercise versus exercise only for chronic patellofemoral pain syndrome: 5-year follow-up
Authors: Jyrki A Kettunen, Arsi Harilainen, Jerker Sandelin, Dietrich Schlenzka, Kalevi Hietaniemi, Seppo Seitsalo, Antti Malmivaara, Urho M Kujala
Journal: British Journal of Sports Medicine (2011)

<h3>Objective</h3> To study the long-term outcome of arthroscopy in patients with chronic patellofemoral pain syndrome (PFPS), the authors conducted a randomised controlled trial. The authors also investigated factors predicting the outcome in patients with PFPS. <h3>Methods</h3> Fifty-six patients with PFPS were randomised into two groups: an arthroscopy group (N=28), treated with knee arthroscopy and an 8-week home exercise programme, and a control group (N=28), treated with a similar 8-week home exercise programme only. The primary outcome was the Kujala score on pain and function at 5-year. Secondary outcomes were visual analogue scales (VASs) to assess activity-related symptoms. <h3>Results</h3> According to the Kujala score, both groups showed a marked improvement during the 5-year follow-up: a mean improvement of 14.7 (95% CI 9.9 to 19.4) in the arthroscopy group and 13.5 (95% CI 8.1 to 18.8) in the controls. No differences between the groups in mean improvement in the Kujala score (group difference 1.2 (95% CI –8.4 to 6.1)) or in the VAS scores were found. None of the investigated factors predicted the long-term outcome, but in most of the cases the treatment result immediately after the exercise programme remained similar also after the 5-year follow-up. <h3>Conclusion</h3> Our RCT, being the first of its kind, indicates that the 5-year outcome in most of the patients with chronic PFPS treated with knee arthroscopy and home exercise programme or with the home exercise programme only is equally good in both groups. Some of the patients in both groups do have long-term symptoms. <h3>Trial registration</h3> Current Controlled Trials ISRCTN 41800323.
Late-onset central hypoventilation syndrome: a family genetic study
Authors: L. S. Doherty, J. L. Kiely, P. C. Deegan, G. Nolan, S. McCabe, A. J. Green, S. Ennis, W. T. McNicholas
Journal: European Respiratory Journal (2007)

Congenital central hypoventilation syndrome is a rare disorder characterised by chronic alveolar hypoventilation, which becomes more pronounced during sleep and may be associated with neurocristopathies, such as Hirchsprung's disease. A mutation in the PHOX2B gene has recently been identified. In a family of both parents and five offspring, detailed clinical assessment, pulmonary function testing, overnight sleep studies and ventilatory responsiveness to progressive hypercapnia (V'(R,CO(2))) were performed, in addition to analysis of known genetic loci for this condition. The father and four of the offspring demonstrated features of central hypoventilation with nonapnoeic oxygen desaturation during sleep and diminished V'(R,CO(2)), despite normal pulmonary function. The lowest sleep saturation was median (range) 79% (67-83%) and V'(R,CO(2)) was 2.1 (0.03-4.3) L x min(-1) x kPa(-1). The normal values for the authors' centre (St Vincent's University Hospital, Dublin, Ireland) are 15-40 L x min(-1) x kPa(-1). An in-frame five amino acid polyalanine expansion of the PHOX2B gene was found in all affected subjects, while the mother and fifth child, who did not have features of central hypoventilation, had a normal PHOX2B gene. Magnetic resonance imaging of the brainstem in one severely affected child was normal. The present study of a unique family confirms that transmission of late-onset congenital central hypoventilation syndrome is autosomal dominant in nature.
Regional Circulatory Adjustments to Moderate and Severe Chronic Anemia in Conscious Dogs at Rest and during Exercise
Authors: STEPHEN F. VATNER, CHARLES B. HIGGINS, DEAN FRANKLIN, DANIEL P. MCKOWN
Journal: Circulation Research (1972)

The successive changes in regional blood flows and resistances due to moderate and severe anemia were studied serially in nine conscious dogs after they recovered from implantation of ultrasonic Doppler transducers or electromagnetic flow probes on the left circumflex coronary, the mesenteric, the renal, and the iliac arteries and pressure gauges or catheters in the aorta. Anemia was induced by progressive phlebotomy and volume replacement over a period of 2-4 weeks. In moderate anemia (average hematocrit 22%) heart rate increased from 73 beats/min to 105 beats/min, and mean arterial pressure fell from 98 mm Hg to 94 mm Hg. Flow increased to the coronary bed by 75% and to the iliac bed by 45%, but flow to the mesenteric bed was not significantly affected and renal flow fell by 9%. Coronary and iliac resistances fell by 45% and 32%, respectively, but mesenteric and renal resistances were not significantly affected. In severe anemia (hematocrit 14%) heart rate increased to 129 beats/min, and mean arterial pressure was at control levels; coronary flow increased by 227%, iliac flow by 102%, mesenteric flow by 29%, and renal flow by 20%. Resistance decreased in the coronary bed by 69%, in the iliac bed by 52%, in the mesenteric bed by 23%, and in the renal bed by 19%. Exercise during severe anemia increased heart rate to 224 beats/min, mean arterial pressure to 114 mm Hg, coronary flow by 34%, and iliac flow by 215%; it reduced mesenteric flow by 59% and renal flow by 48%. Thus, blood flow increased and resistance decreased to all beds studied, indicating that in the resting conscious dog compensatory reduction of visceral flow is not a feature of the cardiovascular response to severe anemia at rest, although a redistribution of regional blood flow does occur. However, the added stress of exercise during severe anemia results in substantial reductions in mesenteric and renal blood flows.
Postmortem angiographic study of degenerative vascular changes in arteries supplying the cervicobrachial region.
Authors: L I Kauppila, A Penttila
Journal: Annals of the Rheumatic Diseases (1994)

To study the prevalence of degenerative changes in the arteries supplying the cervicobrachial region, and their relation to cervical disc degeneration.Fifty postmortem aortic arch angiographies were evaluated for occlusions and variations in the diameter of the vertebral arteries and thyro- and costocervical trunks, as well as for tortuosity, average diameter and the highest cervical level to which the ascending cervical artery, an upward continuation of the thyrocervical trunk, and the deep cervical artery, an upward continuation of the costocervical trunk, ascended.Localised segmental narrowings, usually situated close to the ostia of the arteries, were common, whereas total occlusions were rare. Thirty (60%) of the subjects showed a segmental narrowing at least in one of the six arteries analysed, while only two (4%) showed an occluded artery, which in both the cases was the thyrocervical trunk. Narrowings were most common in vertebral arteries, followed by costocervical and thyrocervical trunks. Segmental narrowings, as well as general tortuosity of the arteries, increased with age. It was also found that ascending and deep cervical arteries did not run as high up in the posterior neck muscles in older people as in younger ones. Twenty three subjects with marked cervical disc degeneration showed on average 2.3 arteries with segmental narrowings, while the corresponding figure for twenty seven subjects without disc degeneration was 0.6. Both the segmental narrowings and the disc degeneration, however, were strongly associated with age, and thus the causality between the former two remained unclear.The study showed that degenerative changes are common in the arteries supplying the cervicobrachial area, indicating that impaired blood flow might play a part in some cervicobrachial disorders.
Glycemic Targets in the Second and Third Trimester of Pregnancy for Women With Type 1 Diabetes
Authors: Michael J.A. Maresh, Valerie A. Holmes, Christopher C. Patterson, Ian S. Young, Donald W.M. Pearson, James D. Walker, David R. McCance
Journal: Diabetes Care (2014)

OBJECTIVE To assess the relationship between second and third trimester glycemic control and adverse outcomes in pregnant women with type 1 diabetes, as uncertainty exists about optimum glycemic targets. RESEARCH DESIGN AND METHODS Pregnancy outcomes were assessed prospectively in 725 women with type 1 diabetes from the Diabetes and Pre-eclampsia Intervention Trial. HbA1c (A1C) values at 26 and 34 weeks’ gestation were categorized into five groups, the lowest, &amp;lt;6.0% (42 mmol/mol), being the reference. Average pre- and postprandial results from an eight-point capillary glucose profile the previous day were categorized into five groups, the lowest (preprandial &amp;lt;5.0 mmol/L and postprandial &amp;lt;6.0 mmol/L) being the reference. RESULTS An A1C of 6.0–6.4% (42–47 mmol/mol) at 26 weeks’ gestation was associated with a significantly increased risk of large for gestational age (LGA) (odds ratio 1.7 [95% CI 1.0–3.0]) and an A1C of 6.5–6.9% (48–52 mmol/mol) with a significantly increased risk of preterm delivery (odds ratio 2.5 [95% CI 1.3–4.8]), pre-eclampsia (4.3 [1.7–10.8]), need for a neonatal glucose infusion (2.9 [1.5–5.6]), and a composite adverse outcome (3.2 [1.3–8.0]). These risks increased progressively with increasing A1C. Results were similar at 34 weeks’ gestation. Glucose data showed less consistent trends, although the risk of a composite adverse outcome increased with preprandial glucose levels between 6.0 and 6.9 mmol/L at 34 weeks (3.3 [1.3–8.0]). CONCLUSIONS LGA increased significantly with an A1C ≥6.0 (42 mmol/mol) at 26 and 34 weeks' gestation and with other adverse outcomes with an A1C ≥6.5% (48 mmol/mol). The data suggest that there is clinical utility in regular measurement of A1C during pregnancy.
Histomorphologic and Histomorphometric Characteristics of Zygapophyseal Joint Remodeling in Ankylosing Spondylitis
Authors: Janine Bleil, Rene Maier, Axel Hempfing, Uwe Schlichting, Heiner Appel, Joachim Sieper, Uta Syrbe
Journal: Arthritis & Rheumatology (2014)

To unravel the mechanisms that control bony ankylosis in ankylosing spondylitis (AS). Histomorphologic and histomorphometric analyses were performed on zygapophyseal joints obtained from 18 patients with AS, 9 patients with osteoarthritis (OA), and 10 cadaver donors without a rheumatic disease (controls). The proteoglycan content of the cartilage was determined by Safranin O staining and the chondrocyte apoptosis according to caspase 3 expression. AS joints were categorized into 3 groups according to the morphology of the joint surfaces and joint space: group 1 were joints with an open joint space, group 2 were joints with cartilaginous fusion, and group 3 were joints with bony fusion of the joint surfaces. Progressive loss of the joint space from group 1 joints to group 3 joints suggests that this grouping corresponds to sequential stages of joint remodeling. Cartilage thickness and subchondral bone plate thickness declined from group 1 to group 3 (P < 0.01). Increased chondrocyte apoptosis rates were found in groups 1 and 2 (P < 0.05), while in group 3, a reduction in the proteoglycan content was found (P < 0.001). Bone marrow replacement and invasion of the subchondral bone plate by fibrous tissue was found predominantly in AS joints in group 2. Cartilage degeneration, indicated by cartilage thinning, enhanced chondrocyte apoptosis, and proteoglycan loss, and subchondral bone thinning, promoted by invasion of the subchondral bone plate by a fibrous tissue originating from the bone marrow, are hallmarks of joint remodeling in AS.
TNF-α enhancement of CD62E mediates adhesion of non–small cell lung cancer cells to brain endothelium via CD15 in lung-brain metastasis
Authors: Samah A. Jassam, Zaynah Maherally, James R. Smith, Keyoumars Ashkan, Federico Roncaroli, Helen L. Fillmore, Geoffrey J. Pilkington
Journal: Neuro-Oncology (2015)

CD15, which is overexpressed on various cancers, has been reported as a cell adhesion molecule that plays a key role in non-CNS metastasis. However, the role of CD15 in brain metastasis is largely unexplored. This study provides a better understanding of CD15/CD62E interaction, enhanced by tumor necrosis factor-α (TNF-α), and its correlation with brain metastasis in non–small cell lung cancer (NSCLC). CD15 and E-selectin (CD62E) expression was demonstrated in both human primary and metastatic NSCLC cells using flow cytometry, immunofluorescence, and Western blotting. The role of CD15 was investigated using an adhesion assay under static and physiological flow live-cell conditions. Human tissue sections were examined using immunohistochemistry. CD15, which was weakly expressed on hCMEC/D3 human brain endothelial cells, was expressed at high levels on metastatic NSCLC cells (NCI-H1299, SEBTA-001, and SEBTA-005) and at lower levels on primary NSCLC (COR-L105 and A549) cells (P < .001). The highest expression of CD62E was observed on hCMEC/D3 cells activated with TNF-α, with lower levels on metastatic NSCLC cells followed by primary NSCLC cells. Metastatic NSCLC cells adhered most strongly to hCMEC/D3 compared with primary NSCLC cells. CD15 immunoblocking decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (P < .0001), confirming a correlation between CD15 and cerebral metastasis. Both CD15 and CD62E expression were detected in lung metastatic brain biopsies. This study enhances the understanding of cancer cell-brain endothelial adhesion and confirms that CD15 plays a crucial role in adhesion in concert with TNF-α activation of its binding partner, CD62E.
Development of Immunohistochemistry Assays to Assess GALNT14 and FUT3/6 in Clinical Trials of Dulanermin and Drozitumab
Authors: Howard M. Stern, Mary Padilla, Klaus Wagner, Lukas Amler, Avi Ashkenazi
Journal: Clinical Cancer Research (2010)

Abstract Purpose: In vitro sensitivity to the proapoptotic receptor agonists dulanermin (rhApo2L/TRAIL) and drozitumab (DR5-agonist antibody) is strongly predicted by the expression of the O-glycosylation enzymes GALNT14 in non–small cell lung cancer (NSCLC) cell lines (among others) and of FUT3/6 in colorectal cancer (CRC) cell lines. We developed immunohistochemistry (IHC) assays that measure GALNT14 and FUT3/6 levels in archival formalin-fixed, paraffin-embedded human tumor tissue to determine marker prevalence in NSCLC and CRC tissue and to enable the future examination of these markers in clinical trials. Experimental Design: GALNT14 or FUT3/6 ELISA-positive hybridoma clones were screened through IHC on cell pellets with known mRNA levels. The specificity of staining was examined in cell lines, normal tissue, and tumor tissue. Results: GALNT14 and FUT3/6 IHC exhibited a golgi staining pattern and correlated with GALNT14 and FUT3/6 (but not GALNT2 and FUT4) mRNA expression levels in cell lines and normal tissues, suggesting specificity. GALNT14 and FUT3/6 H-scores were significantly higher in cell lines sensitive to dulanermin (P = 0.01 and P = 0.0004, respectively) and drozitumab (P = 0.03 and P &amp;lt; 0.0001, respectively) versus resistant cell lines. GALNT14 and FUT3/6 H-scores varied widely, with ∼45% of NSCLC samples exhibiting weak to moderate GALNT14 staining (H-score of at least 25) and 70% of CRC samples exhibiting moderate to strong FUT3/6 staining (H-score of at least 125). Conclusions: GALNT14 and FUT3/6 expression can be assessed in human tumors using sensitive and specific IHC assays. Both assays are being deployed in ongoing clinical trials of dulanermin and drozitumab to assess potential utility for patient selection. Clin Cancer Res; 16(5); 1587–96
A COMPARATIVE STUDY OF THE EFFECTS OF VARIOUS TREATMENTS ON THE CALCIUM AND PHOSPHORUS METABOLISM IN TETANY
Authors: Shih-Hao Liu
Journal: Journal of Clinical Investigation (1928)

Chronic tetany in adults is usually one of two types.In the first type it is associated with loss of parathyroid glands during operations of thyroid.In the second, it occurs in individuals with lesions in the gastro-intestinal tract leading to alkalosis.Cases of chronic tetany in elderly individuals unassociated with either of the above-mentioned conditions are extremely rare in the literature.The following case is recorded on this account as well as in view of metabolic data obtained that may throw some light on the pathogenesis of this type of tetany.
An <i>N</i>-Acetylated Natural Ligand of Human Histocompatibility Leukocyte Antigen (Hla)-B39
Authors: Jesús Yagüe, Iñaki Alvarez, Didier Rognan, Manuel Ramos, Jesús Vázquez, José A. López de Castro
Journal: The Journal of Experimental Medicine (2000)

Sequence-independent interactions involving the free peptidic NH(2) terminus are thought to be an essential feature of peptide binding to classical major histocompatibility complex (MHC) class I proteins. Challenging this paradigm, a natural Nalpha-acetylated ligand of human histocompatibility leukocyte antigen (HLA)-B39 was identified in this study. It matched the NH(2)-terminal sequence of two human helicases, was resistant to aminopeptidase M, and was produced with high yield from a synthetic 30 mer with the sequence of the putative parental protein by the 20S proteasome. This is the first reported natural ligand of classical MHC class I antigens that has a blocked NH(2) terminus.
Sustained-input switches for transcription factors and microRNAs are central building blocks of eukaryotic gene circuits
Authors: Molly Megraw, Sayan Mukherjee, Uwe Ohler
Journal: Genome biology (2013)

WaRSwap is a randomization algorithm that for the first time provides a practical network motif discovery method for large multi-layer networks, for example those that include transcription factors, microRNAs, and non-regulatory protein coding genes. The algorithm is applicable to systems with tens of thousands of genes, while accounting for critical aspects of biological networks, including self-loops, large hubs, and target rearrangements. We validate WaRSwap on a newly inferred regulatory network from Arabidopsis thaliana, and compare outcomes on published Drosophila and human networks. Specifically, sustained input switches are among the few over-represented circuits across this diverse set of eukaryotes.
Mild Traumatic Brain Injury in U.S. Soldiers Returning from Iraq
Authors: Charles W. Hoge, Dennis McGurk, Jeffrey L. Thomas, Anthony L. Cox, Charles C. Engel, Carl A. Castro
Journal: New England Journal of Medicine (2008)

An important medical concern of the Iraq war is the potential long-term effect of mild traumatic brain injury, or concussion, particularly from blast explosions. However, the epidemiology of combat-related mild traumatic brain injury is poorly understood.
Removal of Arg <sup>141</sup> From the α Chain of Human Hemoglobin by Carboxypeptidases N and M
Authors: Bruno Michel Rajko Igić, Valérie Leray, Peter A. Deddish, Ervin G. Erdös
Journal: Circulation Research (1996)

Abstract Both human plasma carboxypeptidase N (CPN) and membrane-bound carboxypeptidase M (CPM) released the C-terminal arginine (α-Arg 141 ) of the α chain of human adult hemoglobin. An arginase contamination present in the hemoglobin preparation, which converted the released arginine to ornithine, was removed by gel filtration. CPM was about 20 times more efficient than CPN or its active subunit in hydrolyzing oxyhemoglobin and cleaved oxyhemoglobin twice as fast as deoxyhemoglobin. The hydrolysis of the peptide bond of α-Arg 141 accelerated the dissociation rate of the tetramer deoxy-des-α-Arg 141 hemoglobin to dimers 2500-fold over that of deoxyhemoglobin, as measured by haptoglobin binding. Moreover, the dissociation of the deoxy-des-α-Arg 141 hemoglobin tetramer to dimers was not affected by 2,3-diphosphoglyceric acid. Des-α-Arg 141 hemoglobin had a higher oxygen affinity (P 50 , 5.51 mm Hg; control, 19.94 mm Hg [P 50 is the partial pressure of oxygen that gives 50% of the saturation of hemoglobin]) and a lower apparent cooperativity (Hill coefficient: n, 1.02; control, 2.24) than unhydrolyzed hemoglobin. After hemoglobin was incubated in human plasma, its oxygen-binding parameters, the P 50 , and the Hill coefficient decreased drastically due to cleavage by CPN. In the perfused rat heart, des-α-Arg 141 hemoglobin was a more effective coronary vasoconstrictor than hemoglobin, possibly because it dissociated to dimers in the coronary vascular bed. A covalently cross-linked hemoglobin was less active than native hemoglobin. The coronary vasoconstriction was caused by multiple factors, including interference with vasodilation by nitric oxide and eicosanoids. Thus, the hydrolysis of hemoglobin by CPM and CPN demonstrated the contribution of the α-Arg 141 residue to sustaining the tetrameric structure of hemoglobin and its normal oxygen affinity and vasoactivity.
Cytoplasmic mislocalization of RNA splicing factors and aberrant neuronal gene splicing in TDP-43 transgenic pig brain
Authors: Guohao Wang, Huaqiang Yang, Sen Yan, Chuan-En Wang, Xudong Liu, Bentian Zhao, Zhen Ouyang, Peng Yin, Zhaoming Liu, Yu Zhao, Tao Liu, Nana Fan, Lin Guo, Shihua Li, Xiao-Jiang Li, Liangxue Lai
Journal: Molecular Neurodegeneration (2015)

TAR DNA-binding protein 43 (TDP-43) is a nuclear protein, but it is redistributed in the neuronal cytoplasm in both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Because small transgenic animal models often lack cytoplasmic TDP-43, how the cytoplasmic accumulation of TDP-43 contributes to these diseases remains unclear. The current study is aimed at studying the mechanism of cytoplasmic pathology of TDP-43.We established transgenic pigs expressing mutant TDP-43 (M337V). This pig model shows severe phenotypes and early death. We found that transgenic TDP-43 is also distributed in the cytoplasm of neuronal cells in the spinal cord and brain. Transgenic TDP-43 interacts with PSF, an RNA splicing factor that associates with NeuN to regulate neuronal RNA splicing. The interaction of TDP-43, PSF and NeuN causes PSF and NeuN mislocalize into the neuronal cytoplasm in transgenic pigs. Consistently, abnormal PSF-related neuronal RNA splicing is seen in TDP-43 transgenic pigs. The cytoplasmic localization of PSF and NeuN as well as abnormal PSF-related neuronal RNA splicing was also found in ALS patient brains.Our findings from a large mammalian model suggest that cytoplasmic mutant TDP-43 could reduce the nuclear function of RNA splicing factors, contributing to neuropathology.
Mini review: linkage between α-Synuclein protein and cognition
Authors: Huda Saleh, Ayeh Saleh, Hailan Yao, Jie Cui, Yong Shen, Rena Li
Journal: Translational Neurodegeneration (2015)

α-synuclein is a protein that plays important roles in cognitive function in the normal brain, although its exact role is not fully understood. However, current studies reveal that defects in α-synuclein function could contribute to various neurodegenerative disorders, such as Parkinson's disease (PD), a disease with symptomatic progression of deterioration in motor and cognitive function. Recent studies show that the level of α -synuclein in cerebrospinal fluid (CSF) is highly correlated with speed of cognitive decline, suggesting a potential role of α-synuclein in cognitive function. In this mini review, we will be focus on literatures of α-synuclein in cognitive function in the non-diseased brain, as well as the impact that defective α-synuclein has on cognition in disease brain. This will be accomplished by assessing the effects of soluble α-synuclein, α-synuclein oligomers, and extracellular α-synuclein transport, on neurodegeneration.