tbuckley/cabot-search huggingface dataset:
Steering simulation performance in patients with obstructive sleep apnoea and matched control subjects
Authors: M Juniper, M.a Hack, C.f George, R.J.o Davies, J.r Stradling
Journal: European Respiratory Journal (2000)

Patients with obstructive pulmonary disease (OSA) have an increased rate of driving accidents, perhaps due to poor vigilance or impaired cognitive skills that influence their driving ability. The authors have assessed whether patients with OSA perform differently to control subjects on a steering simulator which allows the separate assessment of the two visual tasks required for steering a car, immediate positioning on road with reference to the road edges, and assessment of the curve of the oncoming road which allows faster driving. Twelve patients with OSA and 12 control subjects, matched for age, sex and driving experience, performed three 30-min drives with either all the oncoming road visible, only the near part of the road visible, or only the distant part of the road visible. Steering was assessed by measuring the SD around the theoretical perfect path (steering error) and the number of times the driver went "off road". Subjects identified the appearance of target numbers at the four corners of the screen as quickly as possible, thus making the test a divided attention task. Patients with OSA performed significantly less well on the three different road fields as measured by steering error (p&lt;0.001), time to detect the target number (p&lt;0.03), and off road events (p&lt;0.03). The patients appeared to be particularly impaired on the two drives when only part of the road ahead was available to guide steering. This steering simulator, with its more realistic view of the road ahead, identifies impaired performance in patients with obstructive sleep apnoea. In addition it suggests that patients with obstructive sleep apnoea may be more disadvantaged compared to normal subjects when the view of the road ahead is limited (such as in fog).
The Cerebral Cortex
Authors: W. E. L. G. Clark
Journal: BMJ (1951)

The cerebral cortex is a dense aggregation of neuron cell bodies that ranges from 2 to 4 mm in thickness and forms the surface of each cerebral hemisphere. Most of the cerebral cortex is neocortex, consisting of six layers with different populations of neurons. In addition to the laminar organization, there is a perpendicular columnar organization as well. This is especially well studied for the visual cortex, which has columns that receive only visual information from the right eye adjacent to columns that receive only visual information from the left eye. Distinct higher cortical functional areas are devoted to memory, judgment, the planning of complex activities, the processing of language, mathematical calculations, and the construction of an internal image of an individual’s surroundings. The cerebral hemisphere that controls language is called the  dominant hemisphere , is the left hemisphere in about 95% of humans, and includes Broca and Wernicke areas. Damage to either area leads to one of the two classic types of aphasia, Broca aphasia or Wernicke aphasia. Parietal association cortex in the nondominant hemisphere mediates spatial relationships and related selective attention. Damage leads to contralateral neglect and associated symptoms. Prefrontal association cortex mediates the most distinctly human intellectual traits, such as judgment, foresight, a sense of purpose, a sense of responsibility, and a sense of social propriety. Damage leads to a constellation of deficits that are classically described for Phineas Gage.
Dasatinib reverses Cancer-associated Fibroblasts (CAFs) from primary Lung Carcinomas to a Phenotype comparable to that of normal Fibroblasts
Authors: Silke Haubeiss, Jens O Schmid, Thomas E Mürdter, Maike Sonnenberg, Godehard Friedel, Heiko van der Kuip, Walter E Aulitzky
Journal: Molecular Cancer (2010)

Abstract Cancer associated fibroblasts (CAFs) play a critical role for growth, invasion, and metastasis of cancer. Therefore, targeting CAFs with small molecule inhibitors may be an attractive anti-tumor strategy. The current study aims to identify small molecule kinase inhibitors affecting CAF's growth and to characterize the biological effects of active compounds on primary CAFs from lung cancer. We screened two individual CAF strains for their sensitivity to a panel of 160 kinase inhibitors. Five kinase inhibitors were identified inhibiting more than 50% of the growth of both cell lines. Three of them were inhibitors of PDGFR at nanomolar concentrations. Therefore, we further tested the FDA approved PDGFR inhibitors Dasatinib, Nilotinib, Sorafenib, and Imatinib. All 37 CAF strains investigated were highly sensitive to Dasatinib at clinically relevant concentrations. Imatinib was slightly less effective, whereas the inhibitory effects of Nilotinib and Sorafenib were significantly less pronounced. We investigated the effect of Dasatinib on the CAF transcriptome by microarray analysis of 9 individual CAF strains. 492 genes were identified whose expression was changed at least twofold. 104 of these encoded cell cycle related proteins with 97 of them being downregulated by Dasatinib. The majority of regulated genes, however, were of diverse biological functions not directly related to proliferation. We compared this Dasatinib expression signature to previously described differential signatures of normal tissue associated fibroblasts (NAFs) and CAFs and to a signature of fibroblast serum response. There was a significant overlap between genes regulated by Dasatinib and serum repression genes. More importantly, of the 313 genes downregulated by Dasatinib 64 were also reduced in NAFs compared to CAFs. Furthermore, 26 of 179 genes identified as upregulated by Dasatinib were also found to be elevated in NAFs compared to CAFs. These data demonstrate that Dasatinib partially reverses the phenotype of CAFs to a normal fibroblast like phenotype. This is further supported by the finding that incubation of tumor cells with conditioned medium from CAFs pre-incubated with Dasatinib significantly reduced tumor cell proliferation, suggesting that Dasatinib partially reverses the CAF mediated tumor promoting effect. Therefore, targeting CAFs with Dasatinib represents a promising therapeutic principle.
Linkage of pemphigus vulgaris antibody to the major histocompatibility complex in healthy relatives of patients.
Authors: A R Ahmed, A Mohimen, E J Yunis, N M Mirza, V Kumar, E H Beutner, C A Alper
Journal: The Journal of Experimental Medicine (1993)

Pemphigus vulgaris (PV) is an autoimmune disease caused by high concentrations of antibody to an epidermal cadherin. The disease is associated with two kinds of HLA-DR4, DQ8 haplotypes dominantly distributed among Jewish patients, and these plus DR6, DQ5 haplotypes in non-Jewish patients. Low levels of the PV antibody were found in 48% of a total of 120 asymptomatic parents, children, and siblings of 31 patients, thus exhibiting dominant inheritance. The inheritance of these low levels of antibody in asymptomatic relatives was linked to the major histocompatibility complex with a highly significant logarithm of the odds score of 9.07, almost always to a DR4 or DR6 haplotype of the patient. Disease appears to occur in susceptible individuals with low levels of antibody when a second factor, either environmental or genetic, induces high levels, sufficient to produce blisters.
Anti–Transforming Growth Factor β Receptor II Antibody Has Therapeutic Efficacy against Primary Tumor Growth and Metastasis through Multieffects on Cancer, Stroma, and Immune Cells
Authors: Zhaojing Zhong, Kyla Driscoll Carroll, Desiree Policarpio, Carla Osborn, Michael Gregory, Rajiv Bassi, Xenia Jimenez, Marie Prewett, Gregory Liebisch, Kris Persaud, Douglas Burtrum, Su Wang, David Surguladze, Stanley Ng, Heather Griffith, Paul Balderes, Jacqueline Doody, Jonathan D. Schwartz, Hagop Youssoufian, Eric K. Rowinsky, Dale L. Ludwig, Larry Witte, Zhenping Zhu, Yan Wu
Journal: Clinical Cancer Research (2010)

Transforming growth factor beta (TGFbeta) is a pleiotropic cytokine that affects tumor growth, metastasis, stroma, and immune response. We investigated the therapeutic efficacy of anti-TGFbeta receptor II (TGFbeta RII) antibody in controlling metastasis and tumor growth as well as enhancing antitumor immunity in preclinical tumor models.We generated neutralizing antibodies to TGFbeta RII and assessed the antibody effects on cancer, stroma, and immune cells in vitro. The efficacy and mechanism of action of the antibody as monotherapy and in combination with chemotherapy in suppression of primary tumor growth and metastasis were evaluated in several tumor models.Anti-TGFbeta RII antibody blocked TGFbeta RII binding to TGFbeta 1, 2, and 3, and attenuated the TGFbeta-mediated activation of downstream Smad2 kinase, invasion of cancer cells, motility of endothelial and fibroblast cells, and induction of immunosuppressive cells. Treatment with the antibody significantly suppressed primary tumor growth and metastasis and enhanced natural killer and CTL activity in tumor-bearing mice. Immunohistochemistry analysis showed cancer cell apoptosis and massive necrosis, and increased tumor-infiltrating T effector cells and decreased tumor-infiltrating Gr-1+ myeloid cells in the antibody-treated tumors. Fluorescence-activated cell sorting analysis indicated the significant reduction of peripheral Gr-1+/CD11b+ myeloid cells in treated animals. Concomitant treatment with the cytotoxic agent cyclophosphamide resulted in a significantly increased antitumor efficacy against primary tumor growth and metastasis.These preclinical data provide a foundation to support using anti-TGFbeta RII antibody as a therapeutic agent for TGFbeta RII-dependent cancer with metastatic capacity.
Interindividual Variability and Intra-Individual Reproducibility of Glycemic Index Values for Commercial White Bread
Authors: Sonia Vega-López, Lynne M. Ausman, John L. Griffith, Alice H. Lichtenstein
Journal: Diabetes Care (2007)

We sought to assess the intra- and interindividual variability of glycemic index value determinations for white bread using glucose as the reference food.A total of 23 healthy adults (aged 20-70 years) completed up to three sets of two visits per set. Each pair of visits assessed the glycemic response to 50 g available carbohydrates from commercial white bread and glucose, administered in random order. Glycemic index values were calculated by dividing the 2-h incremental area under the serum glucose response curve after each commercial white bread challenge by the mean area under the curve (AUC) for glucose.The mean +/- SE ratio of the AUC after white bread intake by the AUC after glucose intake for the first set of determinations was 78 +/- 15 (n = 23; coefficient of variation [CV] 94%). When using glycemic index values calculated with the subset of participants who completed three sets of tests (n = 14), glycemic index values for each of the three sets of determinations were 78 +/- 10, 60 +/- 5, and 75 +/- 10, respectively. CVs were 50, 28, and 50%, respectively. The mean glycemic index value of these three sets was 71 +/- 6, with a CV of 30%. When an ANOVA approach was applied to these data, the interindividual CV was 17.8%, and the intra-individual variation was 42.8%.These data suggest that in response to a challenge of white bread relative to glucose, within-individual variability is a greater contributor to overall variability than among-individual variability. Further understanding of all the sources of variability would be helpful in better defining the utility of glycemic index values.
Contribution of 92 kDa Gelatinase/Type IV Collagenase in Bronchial Inflammation during Status Asthmaticus
Authors: HASSAN LEMJABBAR, PHILIPPE GOSSET, CATHERINE LAMBLIN, I. TILLIE, DANIEL HARTMANN, BENOIT WALLAERT, ANDRE B. TONNEL, CHANTAL LAFUMA
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

In order to assess inflammatory features related to severe asthma as compared with mild asthma, we investigated the secretion of 92 kDa gelatinase matrix metalloproteinase (MMP-9) in bronchial lavages of six patients undergoing mechanical ventilation (MV) for status asthmaticus (SA) and in six patients with mild asthma. Ten healthy nonventilated patients and four patients under MV without preexisting respiratory disease were also investigated. Patients with SA were characterized by prominent neutrophilic inflammation (82 ± 4% versus 10% in mild asthma). On the basis of enzymatic and immunological analysis, results showed an acute 10- to 160-fold increase of 92 kDa gelatinase (MMP-9) concentration in epithelial lining fluid (ELF) from patients with SA, together with activated forms (46 and 26 kDa) of stromelysin-1 matrix metalloproteinase (MMP-3) and detectable concentration of free metallogelatinolytic activity (1–5 μ g gelatin hydrolyzed/48 h/ml ELF). Concomitant elevated level of tissue inhibitor of metalloproteinase-1 (TIMP-1) was shown only in patients with SA, thus counterbalancing, at least partially, excess of activated 92 kDa gelatinase. Acutely enhanced albumin levels were only observed in patients with SA; in addition, 92 kDa gelatinase and albumin levels were significantly and positively correlated (r = 0.96, p < 0.0001), suggesting that 92 kDa gelatinase may account for increased bronchial permeability in patients with SA. Several arguments support that 92 kDa gelatinase during SA originates both from numerous activated chemoattracted neutrophils and from activated bronchial epithelial cells in response to in situ lung injury. The fact that no relevant change in ELF, albumin, MMP-9, MMP-3, TIMP-1, or laminin degradation products was observed during mild asthma, strongly supports that the mechanism of airway inflammation in SA is quite distinct from that observed in mild asthma.
Erythromelanosis follicularis faciei et colli.
Authors: BO LASTHEIN ANDERSEN
Journal: British Journal of Dermatology (1980)

Journal Article Erythromelanosis follicularis faciei et colli: CASE REPORTS Get access BO LASTHEIN ANDERSEN BO LASTHEIN ANDERSEN Department of Dermatology and Venereology, Odense University Hospital, Odense, Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 102, Issue 3, 1 March 1980, Pages 323–325, https://doi.org/10.1111/j.1365-2133.1980.tb08147.x Published: 01 March 1980
Increased Oxidative Stress and Cardiomyocyte Myofibrillar Degeneration in Patients With Chronic Isolated Mitral Regurgitation and Ejection Fraction &gt;60%
Authors: Mustafa I. Ahmed, James D. Gladden, Silvio H. Litovsky, Steven G. Lloyd, Himanshu Gupta, Seidu Inusah, Thomas Denney, Pamela Powell, David C. McGiffin, Louis J. Dell'Italia
Journal: Journal of the American College of Cardiology (2010)
Oscillations and Filtering Networks Support Flexible Routing of Information
Authors: Thomas Akam, Dimitri M. Kullmann
Journal: Neuron (2010)

The mammalian brain exhibits profuse interregional connectivity. How information flow is rapidly and flexibly switched among connected areas remains poorly understood. Task-dependent changes in the power and interregion coherence of network oscillations suggest that such oscillations play a role in signal routing. We show that switching one of several convergent pathways from an asynchronous to an oscillatory state allows accurate selective transmission of population-coded information, which can be extracted even when other convergent pathways fire asynchronously at comparable rates. We further show that the band-pass filtering required to perform this information extraction can be implemented in a simple spiking network model with a single feed-forward interneuron layer. This constitutes a mechanism for flexible signal routing in neural circuits, which exploits sparsely synchronized network oscillations and temporal filtering by feed-forward inhibition.
Platelet-activating factor augments lipopolysaccharide-induced nitric oxide formation by rat Kupffer cells
Authors: S B Mustafa, K M Howard, M S Olson
Journal: Hepatology (1996)

Acute endotoxic shock is accompanied by an increase in the production of nitric oxide (NO) by several different hepatic cell types. Platelet–activating factor (PAF) is a potent proinflammatory mediator with many pathophysiological actions and, in fact, elevated plasma and tissue levels of PAF are observed in animal models of endotoxic shock. The current study demonstrates that PAF induced nitrite formation, the end product of nitric oxide synthesis, by Kupffer cells in a dose– and time– dependent manner. Moreover, PAF was seen to initiate NO synthase gene expression and protein synthesis. PAF augmented lipopolysaccharide (LPS)–induced expression of inducible nitric oxide synthase messenger RNA (mRNA), protein, nitrite and cyclic guanosine monophosphate (cGMP) levels in Kupffer cells. Treatment of Kupffer cells with actinomycin D or cycloheximide inhibited PAF– and LPS–stimulated nitrite and nitric oxide synthase protein formation confirming that de novo synthesis of the enzyme occurred. In Kupffer cells, the presence of an arginine analog, NG–methyl–L–arginine, attenuated nitrite formation induced by PAF and LPS alone or in combination. L–arginine is the principal substrate for nitric oxide synthase. PAF and LPS individually and in combination induced a time–dependent uptake of L–[3H]–arginine into the Kupffer cell, and this response was sensitive to cycloheximide. The current study indicates that exogenous PAF contributes to the induction of nitric oxide synthase by LPS in cultured rat Kupffer cells.
Morphological differences between hepatocellular carcinoma and hepatocellular carcinomalike lesions
Authors: Ikuko Motohashi, Masahiko Okudaira, Tomoko Takai, Satoshi Kaneko, Noriaki Ikeda
Journal: Hepatology (1992)

In an attempt to provide a quantitative basis for differentiation between well–differentiated hepatocellular carcinoma and hepatocellular carcinomalike lesions (focal nodular hyperplasia, regenerative nodular hyperplasia and hepatocellular adenoma), histopathological and morphometrical analyses were performed on 208 cases of various liver diseases with the aid of an image analyzer. As practical indicators for hepatocellular carcinoma, the following six morphometrical features were established: (a) nuclear shape factor of less than 0.93, (b) coefficient of variance of nuclei of more than 5%, (c) average width of trabecular cords greater than three cells, (d) nucleocytoplasmic ratio increased to more than 0.3, (e) cellular density of more than 40 liver cells and (f) individual nuclear dimension larger than 50 μm 2 . The manifest categories increased with dedifferentiation of cells in hepatocellular carcinoma; the number and degree of cellular and structural atypia became more prominent. Data were analyzed statistically by two multivariate analyses. Logistic analysis was able to correctly separate hepatocellular carcinoma from conditions that were not hepatocellular carcinoma, including hepatocellular carcinomalike lesions. The incidence of 13 descriptive histopathological findings such as fibrous capsule, portal triads and clear–cell clusters were also compared in hepatocellular carcinomalike lesions and hepatocellular carcinomas graded according to Edmondson's classification. Presence of a fibrous capsule, portal triads, mosaiclike patterns and tumor vessels showed statistical differences between hepatocellular carcinomalike lesions and well–differentiated hepatocellular carcinoma by the χ 2 test (p &lt; 0.005). (Hepatology 1992;16:118-126.)
Long-term outcome in systemic lupus erythematosus membranous glomerulonephritis. Lupus Nephritis Collaborative Study Group.
Authors: R P Sloan, M M Schwartz, S M Korbet, R Z Borok
Journal: Journal of the American Society of Nephrology (1996)

The pathology of membranous glomerulonephritis (MGN) in patients with systemic lupus erythematosus (SLE) may be complicated by superimposed glomerular inflammation and/or necrosis. This retrospective study examined whether various histologic patterns of glomerulonephritis (GN) seen on renal biopsy impact upon the prognosis of these patients. Clinical parameters at the time of biopsy were also studied, to determine which might serve as risk factors associated with renal and patient outcome. On the basis of renal biopsy findings, patients were stratified into three pathological study groups by using the World Health Organization (WHO) classification (11). Thirty-six patients had "pure' SLE MGN without (WHO Va) or with (WHO Vb) mesangial hypercellularity. Fifteen patients had SLE MGN with segmental endocapillary proliferation and/or necrosis in < 50% of glomeruli (WHO Vc < 50%). Twenty-eight patients had SLE MGN with endocapillary proliferation and/or necrosis in > or = 50% of glomeruli (MGN with segmental proliferation and/or necrosis in > 50%, WHO Vc > or = 50%, or MGN with superimposed diffuse endocapillary proliferation, WHO Vd). There were no significant differences in sex, age, or race among patients in the three study groups. There was a trend for increasing serum creatinine concentration, urine protein excretion, and diastolic blood pressure, and decreasing the third component of serum complement (C3) to be associated with increasing glomerular inflammation, and these differences were significant when Vc > or = 50% and Vd was compared with Va and Vb (P < 0.05). The 5- and 10-yr actuarial survival rates without reaching the study outcomes of death or renal replacement therapy for the three study groups were 86, 72, and 49% and 72, 48, and 20% respectively, and the differences between Va and Vb and Vc > 50% and Vd were significant (P < 0.05). SLE MGN has a heterogeneous course and outcome, and this variability is related to the extent and degree of glomerulonephritis seen on renal biopsy. The only clinical factor with an independent risk of reaching a study outcome was elevation of the initial serum creatinine concentration (Cox regression analysis). This predictive value appears to apply only to patients with the most severe forms of glomerulonephritis, suggesting that they may have a different natural history and/or a response to therapy than SLE MGN with less widespread glomerular inflammation and/or necrosis.