tbuckley/cabot-search huggingface dataset:
Activity-Dependent Spinal Cord Plasticity in Health and Disease
Authors: Jonathan R Wolpaw, Ann M Tennissen
Journal: Annual Review of Neuroscience (2001)

▪ Abstract Activity-dependent plasticity occurs in the spinal cord throughout life. Driven by input from the periphery and the brain, this plasticity plays an important role in the acquisition and maintenance of motor skills and in the effects of spinal cord injury and other central nervous system disorders. The responses of the isolated spinal cord to sensory input display sensitization, long-term potentiation, and related phenomena that contribute to chronic pain syndromes; they can also be modified by both classical and operant conditioning protocols. In animals with transected spinal cords and in humans with spinal cord injuries, treadmill training gradually modifies the spinal cord so as to improve performance. These adaptations by the isolated spinal cord are specific to the training regimen and underlie new approaches to restoring function after spinal cord injury. Descending inputs from the brain that occur during normal development, as a result of supraspinal trauma, and during skill acquisition change the spinal cord. The early development of adult spinal cord reflex patterns is driven by descending activity; disorders that disrupt descending activity later in life gradually change spinal cord reflexes. Athletic training, such as that undertaken by ballet dancers, is associated with gradual alterations in spinal reflexes that appear to contribute to skill acquisition. Operant conditioning protocols in animals and humans can produce comparable reflex changes and are associated with functional and structural plasticity in the spinal cord, including changes in motoneuron firing threshold and axonal conduction velocity, and in synaptic terminals on motoneurons. The corticospinal tract has a key role in producing this plasticity. Behavioral changes produced by practice or injury reflect the combination of plasticity at multiple spinal cord and supraspinal sites. Plasticity at multiple sites is both necessary—to insure continued performance of previously acquired behaviors—and inevitable—due to the ubiquity of the capacity for activity-dependent plasticity in the central nervous system. Appropriate induction and guidance of activity-dependent plasticity in the spinal cord is an essential component of new therapeutic approaches aimed at maximizing function after spinal cord injury or restoring function to a newly regenerated spinal cord. Because plasticity in the spinal cord contributes to skill acquisition and because the spinal cord is relatively simple and accessible, this plasticity is a logical and practical starting point for studying the acquisition and maintenance of skilled behaviors.
Increased C reactive protein in response to acute stress in patients with rheumatoid arthritis
Authors: J J C S Veldhuijzen van Zanten
Journal: Annals of the Rheumatic Diseases (2005)

To assess the effects of acute stress on inflammatory, haemostatic, rheological, and haemodynamic activity in patients with rheumatoid arthritis (RA) in comparison with patients with osteoarthritis (OA).21 patients with RA and 10 with OA underwent a brief mental stress task while standing. Inflammatory, haemostatic, rheological, and haemodynamic variables were measured at baseline, during the task, and at recovery.At baseline, erythrocyte sedimentation rate and fibrinogen were higher in RA than OA. White blood cell count, fibrinogen, blood pressure, and pulse rate increased, whereas prothrombin time and plasma volume decreased during the task in both patient groups. The stress task increased C reactive protein (CRP) only in patients with RA, and more specifically in those patients with RA with high disease activity.The increase in the inflammatory marker CRP, which was specific to patients with RA, combined with the haemostatic, rheological, and haemodynamic reactions to the stress task, over and above the already high baseline levels, could underlie the increased risk for myocardial infarction in this vulnerable patient group.
Fatal poisoning among young children from diethylene glycol-contaminated acetaminophen - Nigeria, 2008-2009.
Authors: A. Abubukar, E. Awosanya, O. Badaru, S. Haladu, P. Nguku, P. Edwards, R. Noe, M. Teran-Maciver, A. Wolkin, L. Lewis, M. Nguyen
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus
Authors: Joost J. Smit, Brian D. Rudd, Nicholas W. Lukacs
Journal: The Journal of Experimental Medicine (2006)

Respiratory syncytial virus (RSV) infection is widely spread and is a major cause of bronchiolitis in infants and high-risk adults, often leading to hospitalization. RSV infection leads to obstruction and inflammation of the airways and induction of innate and acquired immune responses. Because dendritic cells (DCs) are essential in the elicitation of these immune responses, we investigated the presence and the role of dendritic cell subtypes upon RSV infection in the lung. Here, we report that RSV infection increased the number of both conventional and plasmacytoid dendritic cells in the lung and the lung-draining lymph nodes. In particular, the increase in plasmacytoid dendritic cell numbers was sustained and lasted until 30 d after infection. Depletion of plasmacytoid dendritic cells resulted in decreased RSV clearance. In addition, depletion of plasmacytoid dendritic cells resulted in an exacerbation of all manifestations of immune-mediated pathology caused by RSV infection. In conclusion, this study demonstrates that both conventional and plasmacytoid dendritic cells are attracted to the site of RSV infection. It is demonstrated that plasmacytoid dendritic cells play a protective role during RSV infection by modulation of local immune responses.
Deficiency of cathepsin S reduces atherosclerosis in LDL receptor–deficient mice
Authors: Galina K. Sukhova, Yaou Zhang, Jie-Hong Pan, Youichiro Wada, Takashi Yamamoto, Makoto Naito, Tatsuhiko Kodama, Sotirios Tsimikas, Joseph L. Witztum, Michael L. Lu, Yasuhiko Sakara, Michael T. Chin, Peter Libby, Guo-Ping Shi
Journal: Journal of Clinical Investigation (2003)

Human atherosclerotic lesions overexpress the lysosomal cysteine protease cathepsin S (Cat S), one of the most potent mammalian elastases known. In contrast, atheromata have low levels of the endogenous Cat S inhibitor cystatin C compared with normal arteries, suggesting involvement of this protease in atherogenesis. The present study tested this hypothesis directly by crossing Cat S-deficient (CatS(-/-)) mice with LDL receptor-deficient (LDLR(-/-)) mice that develop atherosclerosis on a high-cholesterol diet. Compared with LDLR(-/-) mice, double-knockout mice (CatS(-/-)LDLR(-/-)) developed significantly less atherosclerosis, as indicated by plaque size (plaque area and intimal thickening) and stage of development. These mice also had markedly reduced content of intimal macrophages, lipids, smooth muscle cells, collagen, CD4(+) T lymphocytes, and levels of IFN-gamma. CatS(-/-)LDLR(-/-) monocytes showed impaired subendothelial basement membrane transmigration, and aortas from CatS(-/-)LDLR(-/-) mice had preserved elastic laminae. These findings establish a pivotal role for Cat S in atherogenesis.
Bone anabolic changes progress in psoriatic arthritis patients despite treatment with methotrexate or tumour necrosis factor inhibitors
Authors: Stephanie Finzel, Sebastian Kraus, Sarah Schmidt, Axel Hueber, Juergen Rech, Klaus Engelke, Matthias Englbrecht, Georg Schett
Journal: Annals of the Rheumatic Diseases (2012)

Objectives To investigate whether methotrexate or tumour necrosis factor inhibitors (TNFi) affect osteophyte formation in patients with psoriatic arthritis (PsA). Methods 41 patients with PsA were examined for the presence of osteophytes and erosions at the metacarpophalangeal joints by high-resolution micro-CT imaging. The size of each individual lesion was quantified at baseline and 1-year follow-up in PsA patients treated with TNFi (N=28) or methotrexate (N=13). Groups were comparable for age, sex, disease duration and activity and baseline burden of osteophytes. Results In total, 415 osteophytes (TNFi N=284, methotrexate N=131) were detected. Osteophyte size increased significantly from baseline to follow-up in the TNFi group (mean±SEM change +0.23±0.02 mm; p&lt;0.0001) and the methotrexate group (+0.27±0.03 mm, p&lt;0.0001). In both treatment groups, the majority of osteophytes showed progression (TNFi 54.3%, methotrexate 61.1%), whereas regression of lesions was rare (less than 10%). In contrast to osteophytes, clinical disease activity decreased in both groups of PsA patients and erosions showed an arrest of progression in both groups. Conclusions Osteophytes progress in PsA patients treated with either methotrexate or TNFi. These data provide the first evidence that pathological bone formation in the appendicular skeleton of patients with PsA is not affected by current antirheumatic treatment strategies.
Cancer Mortality and Morbidity Among Rubber Workers&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: R R Monson, L J Fine
Journal: JNCI Journal of the National Cancer Institute (1978)

Mortality and morbidity from cancer among a cohort of 13,570 white male rubber workers were examined. Each man worked for at least 5 years at the Akron, Ohio, plant of the B. F. Goodrich Company. The potential period of follow-up was from January 1, 1940 to June 30, 1976. Departmental work histories were based primarily on records maintained by Local no. 5, United Rubber Workers. The occurrence of cancer was measured by death certificates and by a survey of Akron-area hospital tumor registries from 1964 to 1974. Two types of analyses were made: 1) an external comparison of mortality rates of rubber workers versus rates of U.S. white males, and 2) an internal comparison of cancer morbidity rates among persons who were employed in various work areas of the plant. Excess cases of specific cancers (observed/expected numbers) among workers in specific work areas included: stomach and intestine: rubber making (30/14.4); lung: tire curing (31/14.1), fuel cells and/or deicers (46/29.1); bladder: chemical plant (6/2.4), and tire building (16/10.7); skin cancer: tire assembly (12/1.9); brain cancer: tire assembly (8/2.0); lymphatic cancer: tire building (8/3.2); and leukemia: calendering (8/2.2), tire curing (8/2.6), tire building (12/7.5), elevators (4/1.4), tubes (4/1.6), and rubber fabrics (4/1.1). Agents that may be responsible for these excesses were considered.
Alcohol, Height, and Adiposity in Relation to Estrogen and Prolactin Levels in Postmenopausal Women
Authors: S. E. Hankinson, W. C. Willett, J. E. Manson, D. J. Hunter, G. A. Colditz, M. J. Stampfer, C. Longcope, F. E. Speizer
Journal: JNCI Journal of the National Cancer Institute (1995)

Alcohol use, height, and postmenopausal adiposity have each been positively associated with postmenopausal breast cancer risk in most epidemiologic studies. The mechanism underlying these associations is unclear, although an effect of these factors on hormone levels has been hypothesized. Few previous studies have evaluated the relationship of either alcohol consumption or height with plasma hormone levels. A positive association between adiposity and plasma estrogen levels in postmenopausal women has been reported consistently.Using archived frozen plasma samples and corresponding data from participants in the Nurses' Health Study, we determined plasma hormone levels and assessed these levels in relation to alcohol consumption, height, and adiposity among postmenopausal women.Blood samples were collected from a subset of participants in the Nurses' Health Study in 1989 and 1990, then stored in liquid nitrogen. Hormone concentrations in 217 archived plasma samples (from healthy postmenopausal women) were analyzed in 1993. Spearman correlation coefficients were calculated to assess the linear association between alcohol consumption during the previous year (mean daily intake in grams per day ascertained from semiquantitative food-frequency questionnaires completed in 1990 or 1991), height, and adiposity (as measured by body mass index [BMI] in kg/m2, with weight reported at time of blood collection), and plasma hormone levels. Two-sided P values were also calculated.After controlling for age, height, smoking status, and BMI, alcohol consumption was positively associated with estrone sulfate concentrations (r = .17; P = .02); no statistically significant association was noted for the other plasma hormones measured. Mean plasma estrone sulfate levels were 159 pg/mL in women who reported no alcohol use versus 211 pg/mL in women consuming 30 g or more of alcohol per day. After adjusting for the other covariates, we observed a strong positive correlation between BMI and plasma estrogens (r ranging from .37 for estrone and estrone sulfate to .63 for bioavailable estradiol, with all P values < or = .01; prolactin was the only hormone unassociated with BMI, r = -.01). Height was unrelated to either plasma estrogens or prolactin.BMI and alcohol use were positively associated with postmenopausal plasma estrogen and estrone sulfate levels, respectively.The association of alcohol consumption and postmenopausal obesity with subsequent breast cancer risk might be mediated, at least in part, through an influence on postmenopausal plasma estrogen levels. Additional studies are needed to further quantify the relationship between alcohol consumption and plasma hormone levels and to elucidate the physiologic basis for this association.
Velocity profiles of blood platelets and red blood cells flowing in arterioles of the rabbit mesentery.
Authors: G J Tangelder, D W Slaaf, A M Muijtjens, T Arts, M G oude Egbrink, R S Reneman
Journal: Circulation Research (1986)

Velocity profiles were determined in rabbit mesenteric arterioles (diameter 17-32 micron). A good spatial resolution was obtained by using the blood platelets as small and natural markers of flow, providing for the first time in vivo detailed, quantitative information about the shape of the velocity profiles in microvessels. In some experiments red blood cell velocity profiles were recorded as well. Easy detection of the cells of interest could be achieved by labelling them selectively with a fluorescent dye and visualizing them by intravital fluorescence video microscopy, using flashed illumination. Pairs of flashes were given with a short, preset time interval between both flashes, yielding in one TV picture two images of the same cell displaced over a certain distance for the given time interval. Velocity and mean radial position of cells, flowing within an optical section around the median plane of the vessel, were determined. The shape of the velocity profiles of platelets and red blood cells was similar. The profiles were flattened as compared to a parabola, both in systole and diastole. Vessel diameter did not change measurably during the cardiac cycle. As an index of the degree of blunting of the profiles, the ratio of the maximal and mean velocity of the profile was used, which is 2 for a parabola and 1 for complete plug flow. The index ranged from 1.39 to 1.54 (median 1.50), and increased with vessel diameter. Calculations showed that the blunting of the profiles cannot be explained by an influence of the finite depth of the optical section.
Increasing the Decrement in Insulin Secretion Improves Glucagon Responses to Hypoglycemia in Advanced Type 2 Diabetes
Authors: Zarmen Israelian, Niyaz R. Gosmanov, Ervin Szoke, Manju Schorr, Syed Bokhari, Philip E. Cryer, John E. Gerich, Christian Meyer
Journal: Diabetes Care (2005)

In advanced beta-cell failure, counterregulatory glucagon responses may be impaired due to a reduced decrement in insulin secretion during the development of hypoglycemia. The present studies were therefore undertaken to test the hypothesis that these may be improved by increasing this decrement in insulin secretion.Twelve subjects with type 2 diabetes who have been insulin requiring were studied as a model of advanced beta-cell failure. Glucagon responses were examined during a 90-min hypoglycemic clamp (approximately 2.8 mmol/l) on two separate occasions. On one occasion, tolbutamide was infused for 2 h before the clamp so that the decrement in insulin secretion during the induction of hypoglycemia would be increased. On the other occasion, normal saline was infused as a control.Before the hypoglycemic clamp, infusion of tolbutamide increased insulin secretion approximately 1.9-fold (P < 0.001). However, during hypoglycemia, insulin secretion decreased to similar rates on both occasions (P = 0.31) so that its decrement was approximately twofold greater following the tolbutamide infusion (1.63 +/- 0.20 vs. 0.81 +/- 0.17 pmol x kg(-1) x min(-1), P < 0.001). This was associated with more than twofold-greater glucagon responses (42 +/- 11 vs. 19 +/- 8 ng/l, P < 0.002) during the hypoglycemic clamp but unaltered glucagon responses to intravenous arginine immediately thereafter (449 +/- 50 vs. 453 +/- 50 ng/l, P = 0.78).Increasing the decrement in insulin secretion during the development of hypoglycemia improves counterregulatory glucagon responses in advanced beta-cell failure. These findings further support the concept that the impaired counterregulatory glucagon responses in advanced beta-cell failure may at least partially be due to a reduced decrement in insulin secretion.
Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase Inhibition Results in Biphasic Alteration of Epidermal Homeostasis with Keratinocytic Apoptosis and Pigmentation Disorders
Authors: Karin Schad, Katrin Baumann Conzett, Marie C. Zipser, Valérie Enderlin, Jivko Kamarashev, Lars E. French, Reinhard Dummer
Journal: Clinical Cancer Research (2010)

Raf/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway is constitutively activated in melanoma. AZD6244 blocks MEK1/2, inhibiting ERK phosphorylation. We focus on associated cutaneous toxicity and we attempt to understand the underlying pathophysiology and design treatment strategies.Dermatologic conditions of 22 patients with unresectable melanoma stage III/IV in a phase II trial were evaluated. Thirteen patients received AZD6244 initially, and nine patients were treated with AZD6244 following tumor progression with temozolomide. Biopsies were compared with matched controls in normal skin. Immunohistochemistry was performed. Half-side treatment of acute skin toxicity compared therapeutic options.Nineteen of 22 (86%) AZD6244-treated patients presented with cutaneous eruptions. Seventeen patients (77%) developed acute papulopustular rash. Chronic skin changes included xerosis, paronychia, and fissured fingertips, resembling cutaneous toxicity of epidermal growth factor receptor inhibition. In addition, we observed reduced pigmentation of hair and skin. Histology of acute skin lesions revealed a significant increase of apoptotic keratinocytes (P = 0.0008), focal neutrophilic infiltrates, destruction of the adnexal structures by neutrophils, and reduced cytokeratins. A significant proliferation shift from basal to suprabasal keratinocytes was shown in acute and chronic lesions. The number and viability of melanocytes was not affected. Corticosteroids plus antibacterial topical therapy ameliorate acute skin toxicity.AZD6244-associated skin reactions partly overlap with those observed upon epidermal growth factor receptor inhibition. Additionally, pigmentation of skin and hair is affected. The interruption of the MEK signaling pathway results in an acute keratinocyte stress response with disturbed epidermal homeostasis, inflammation, and tissue damage. Chronic adaptation controls inflammatory tissue damage but leads to cutaneous malfunctions that explain chronic skin toxicity.
Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: An international consensus
Authors: Lasse R. Braathen, Rolf-Markus Szeimies, Nicole Basset-Seguin, Robert Bissonnette, Peter Foley, David Pariser, Rik Roelandts, Ann-Marie Wennberg, Colin A. Morton
Journal: Journal of the American Academy of Dermatology (2006)
Molecular Phylogeny of Early Vertebrates: Monophyly of the Agnathans as Revealed by Sequences of 35 Genes
Authors: Naoko Takezaki, Felipe Figueroa, Zofia Zaleska-Rutczynska, Jan Klein
Journal: Molecular Biology and Evolution (2003)

Extant vertebrates are divided into three major groups: hagfishes (Hyperotreti, myxinoids), lampreys (Hyperoartia, petromyzontids), and jawed vertebrates (Gnathostomata). The phylogenetic relationships among the groups and within the jawed vertebrates are controversial, for both morphological and molecular studies have rendered themselves to conflicting interpretations. Here, we use the sequences of 35 nuclear protein-encoding genes to provide definitive evidence for the monophyly of the Agnatha (jawless vertebrates, a group encompassing the hagfishes and lampreys). Our analyses also give a strong support for the separation of Chondrichthyes (cartilaginous fishes) before the divergence of Osteichthyes (bony fishes) from the other gnathostomes.
Paediatric-onset psoriasis is associated with<i>ERAP1</i>and<i>IL23R</i>loci,<i>LCE3C_LCE3B</i>deletion and<i>HLA-C*06</i>
Authors: J.G.M. Bergboer, A.M. Oostveen, M.E.A. de Jager, M. den Heijer, I. Joosten, P.C.M. van de Kerkhof, P.L.J.M. Zeeuwen, E.M.G.J. de Jong, J. Schalkwijk, M.M.B. Seyger
Journal: British Journal of Dermatology (2012)

Recent genome-wide association studies have identified several genetic risk factors for psoriasis, but data on their association with age at onset are lacking.To compare the association between known risk alleles and psoriasis in well-defined cohorts with paediatric- and adult-onset psoriasis.Based on previous studies we selected seven genes and loci associated with psoriasis. Patients with paediatric-onset (< 18 years) and adult-onset psoriasis (≥ 18 years) and controls were genotyped. Genotype frequencies were compared between controls (n = 450) and all cases (n = 217), and between controls and cases stratified for confirmed age at onset (paediatric onset n = 80, adult onset n = 85).Paediatric-onset psoriasis showed a significant association with single nucleotide polymorphisms in the ERAP1 (P = 0.042) and IL23R loci (P = 0.042), LCE3C_LCE3B-del (P = 0.003) and HLA-C*06 (P = 1.72 × 10(-19)) when compared with the control group. A significant association of these four genes was also demonstrated when all psoriasis cases were compared with controls. In adult-onset psoriasis a significant association was found for HLA-C*06 (P = 5.11 × 10(-6)) and for LCE3C_LCE3B-del (P = 0.042). No associations were found for the IFIH1, IL12B and TRAF3IP2 loci.Notwithstanding the small cohort sizes, we demonstrated an association with established and recently discovered genetic risk factors in paediatric-onset psoriasis including genes involved in epidermal barrier function and adaptive immunity. Our data suggest that heritable factors may play a more important role in paediatric-onset psoriasis than in adult-onset psoriasis.
International Consensus Guidelines for Surgical Resection of Mucinous Neoplasms Cannot Be Applied to All Cystic Lesions of the Pancreas
Authors: Mandeep S. Sawhney, Siwar Al-Bashir, Marcelo S. Cury, Alphonso Brown, Ram Chuttani, Douglas K. Pleskow, Mark P. Callery, Charles M. Vollmer
Journal: Clinical Gastroenterology and Hepatology (2009)