tbuckley/cabot-search huggingface dataset:
Neuraminidase and Cell Viability: Failure to Detect Cytotoxic Effects With Dye-Exclusion Techniques 2
Authors: John M. Yuhas, R. E. Toya, N. H. Pazmiño
Journal: JNCI Journal of the National Cancer Institute (1974)

The effects of in vitro incubation of line-1 carcinoma cells with Vibrio cholerae neuraminidase (VCN) were studied in vivo and in vitro. At 25-200 U/106 cella/ml, VCN had no effect on the ability of line-1 cells to exclude either eosin or trypan blue; i.e., VCN did not affect viability. When, however, the viability of these same cells was assayed in vitro by either colony formation or 3H-thymidine incorporation, a concentration-dependent reduction in viability was observed. At the highest concentration tested, 200 U/106 cells/ml, 73–84% cytotoxicity was observed. This toxicity of VCN was not related to the prior treatment of the cells with trypsin and could be abolished by heat-inactivation of the VCN before use. After correction of the data for VCN-induced toxicity, VCN-treated cells were as efficient as untreated cells in producing tumors in vivo and gave no evidence of a heightened ability to sensitize the mice to subsequent tumor challenge. We concluded, therefore, that VCN was toxic to line-1 cells, that this toxicity was not detectable by dye-exclusion techniques, and that VCN treatment did not increase the antigenicity of line-1 cells.
Neural respiratory drive in healthy subjects and in COPD
Authors: C. J. Jolley, Y-M. Luo, J. Steier, C. Reilly, J. Seymour, A. Lunt, K. Ward, G. F. Rafferty, M. I. Polkey, J. Moxham
Journal: European Respiratory Journal (2008)

The aim of the present study was to use the diaphragm electromyogram (EMG(di)) to compare levels of neural respiratory drive (NRD) in a cohort of healthy subjects and chronic obstructive pulmonary disease (COPD) patients, and to investigate the relationship between NRD and pulmonary function in COPD. EMG(di) was recorded at rest and normalised to peak EMG(di) recorded during maximum inspiratory manoeuvres (EMG(di) % max) in 100 healthy subjects and 30 patients with COPD, using a multipair oesophageal electrode. EMG(di) was normalised to the amplitude of the diaphragm compound muscle action potential (CMAP(di,MS)) in 64 healthy subjects. The mean+/-sd EMG(di) % max was 9.0+/-3.4% in healthy subjects and 27.9+/-9.9% in COPD patients, and correlated with percentage predicted forced expiratory volume in one second, vital capacity and inspiratory capacity in patients. EMG(di) % max was higher in healthy subjects aged 51-80 yrs than in those aged 18-50 yrs (11.4+/-3.4 versus 8.2+/-2.9%, respectively). Observations in the healthy group were similar when peak EMG(di) or CMAP(di,MS) were used to normalise EMG(di). Levels of neural respiratory drive were higher in chronic obstructive pulmonary disease patients than healthy subjects, and related to disease severity. Diaphragm compound muscle action potential could be used to normalise diaphragm electromyogram if volitional inspiratory manoeuvres could not be performed, allowing translation of the technique to critically ill and ventilated patients.
Response of blood gas tensions to aminophylline and isoprenaline in patients with asthma
Authors: E. Tai, J. Read
Journal: Thorax (1967)

Aminophylline and isoprenaline, two drugs widely used in the management of asthma, have a pulmonary vasodilator action as well as a bronchodilator action. If regional pulmonary vasoconstriction in poorly ventilated parts of the lungs is a significant compensatory phenomenon in asthma, the effects of administration of these agents on gas exchange would depend on the relative magnitudes of bronchodilator action and pulmonary vasodilator action in the individual patient. If vasodilator action were greater than bronchodilator action in significant portions of the lungs, maldistribution of ventilation-blood flow ratios would increase and arterial oxygen tension might fall. In 40 patients with chronic asthma, arterial blood gas tensions, minute ventilation, alveolar-arterial oxygen tension gradient, physiological dead space/tidal volume ratio, and oxygen consumption were measured before and at intervals up to 20 to 40 minutes after the administration of various agents: in 13 patients, 250 mg. of aminophylline intravenously; in 16 patients, six deep inhalations of 1% isoprenaline aerosol; in 11 patients, after various control procedures. There were no significant changes following the control procedures. Administration of both aminophylline and isoprenaline was followed by increases of F.E.V.<sub>1·0</sub> and increases of minute ventilation. Despite these changes, five patients in each group showed a fall of arterial Po<sub>2</sub> of 5 mm. Hg or more. This was accompanied by an increase of alveolar-arterial oxygen tension gradient. It was concluded that the decreases of arterial blood Po<sub>2</sub> resulted from reversal of pre-existing, compensatory, regional pulmonary vasoconstriction by the pulmonary vasodilator action of each drug in some subjects.
Secondary findings and carrier test frequencies in a large multiethnic sample
Authors: Tomasz Gambin, Shalini N. Jhangiani, Jennifer E. Below, Ian M. Campbell, Wojciech Wiszniewski, Donna M. Muzny, Jeffrey Staples, Alanna C. Morrison, Matthew N. Bainbridge, Samantha Penney, Amy L. McGuire, Richard A. Gibbs, James R. Lupski, Eric Boerwinkle
Journal: Genome Medicine (2015)
Acetaldehyde-modified epitopes in liver biopsy specimens of alcoholic and nonalcoholic patients: Localization and association with progression of liver fibrosis†
Authors: Axel Holstege, Pierre Bedossa, Thierry Poynard, Michael Kollinger, Jean Claude Chaput, Karl Houglum, Mario Chojkier
Journal: Hepatology (1994)

Acetaldehyde, the first product of ethanol oxidation, has been shown to stimulate collagen gene expression and to form protein-acetaldehyde adducts. Because little is known about these adducts in human liver tissue, we assessed, with an immunohistochemical procedure, the presence and location of acetaldehyde-protein adducts in liver biopsy specimens of alcoholic patients. In addition, we correlated the presence of adducts with the progression or subsequent occurrence of liver fibrosis. The group included 106 patients with high alcohol consumption (&gt;90 gm ethanol/day for the last 5 yr), 10 nonalcoholic patients with normal livers and 23 patients with other liver diseases. Sixty-four of the 106 alcoholic patients had a second liver biopsy, whose specimen was used to assess the progression of liver fibrosis. Polyclonal antibodies were produced against homologous low-density lipo-protein purified from rabbit serum and modified in vitro in the presence of acetaldehyde. Protein-acetaldehyde adducts could be detected by immunohistochemistry in biopsy specimens of 90 alcoholic patients (85), in none of the 10 nonalcoholic patients with normal livers and in 65 of the patients with nonalcoholic liver disease. Acetaldehyde-modified epitopes were detected in the intracellular and extracellular compartment. Intracellular protein-acetaldehyde adducts were localized in the cytoplasm of hepatocytes with a more intense staining in zone 3. No correlation existed between the intensity of intracellular staining and the histologically assessed severity of liver disease. Extracellular acetaldehyde-modified epitopes were detected in 55 (52) biopsy specimens of alcoholic patients, with 33 of 39 (85) patients with alcoholic hepatitis or alcoholic hepatitis in cirrhosis, in none of the 10 nonalcoholic patients with normal livers and in 3 (13) of 23 patients with other liver diseases. Extracellular protein-acetaldehyde adducts were colocalized within the extracellular matrix. A brighter staining was seen in areas of histologically assessed active fibrogenesis and no or low staining in the well-organized older fibrous tissue. The presence of extracellular acetaldehyde adducts in the first biopsy specimen was significantly correlated to progression of liver fibrosis in the second biopsy specimen (p &lt; 0.05). The results of our study indicate that covalent crosslinks between acetaldehyde and proteins could be involved in the pathogenesis of liver fibrosis. (Hepatology 1994;19:367-374).
Rapidly progressive obstructive cardiomyopathy in infants with Noonan's syndrome. Report of two cases.
Authors: H D Hirsch, H Gelband, O Garcia, S Gottlieb, D M Tamer
Journal: Circulation (1975)

Two patients with hypertrophic obstructive cardiomyopathy and Noonan's syndrome are presented. Both patients were found at postmortem examination to have gross malformation of the mitral valve and obliteration of the left ventricle due to muscle hypertrophy. Each case demonstrated similar clinical, echocardiographic, and angiographic findings. The poor response to medical and surgical therapy are noted.
Refractory massive pleural effusion in systemic lupus erythematosus treated with talc poudrage.
Authors: J L Kaine
Journal: Annals of the Rheumatic Diseases (1985)

The case of a 31-year-old black male is presented with recurrent pleural effusion secondary to active SLE. Treatment with corticosteroids, azathioprine, plaquenil, and tetracycline pleural sclerosis was unsuccessful. Disease control was finally achieved by pleural talc poudrage.
Risk of Metabolic Syndrome and Diabetes Among Young Twins and Singletons in Guinea-Bissau
Authors: Morten Bjerregaard-Andersen, Lone Hansen, Leontina I. da Silva, Luis C. Joaquím, Ditte E. Hennild, Lene Christiansen, Peter Aaby, Christine S. Benn, Kaare Christensen, Morten Sodemann, Dorte M. Jensen, Henning Beck-Nielsen
Journal: Diabetes Care (2013)

Twins in Africa may be at increased risk of metabolic disorders due to strained conditions in utero, including high exposure to infections. We studied metabolic syndrome (MS) and diabetes mellitus (DM) among young twins and singletons in Guinea-Bissau.The study was cross-sectional and occurred from October 2009 until August 2011 at the Bandim Health Project, a demographic surveillance site in the capital Bissau. Twins and singleton controls between 5 and 32 years were visited at home. Fasting blood samples for metabolic measurements were collected. Zygosity was established genetically for a subset. DM was defined as HbA1c ≥6.5% (48 mmol/mol) and MS by the International Diabetes Federation criteria.HbA1c was available for 574 twins and 463 singletons. Mean age was 15.3 years versus 15.8 years, respectively. Eighteen percent of twins were monozygotic. There were no DM cases among twins but one among singletons. A total of 1.4% (8 of 574) of twins had elevated HbA1c (6.0-6.4%, 42-46 mmol/mol) compared with 2.4% (11 of 463) of singletons (P = 0.28). Mean HbA1c was 5.3% (34 mmol/mol) for both groups. MS data were available for 364 twins and 360 singletons. The MS prevalence was 3.0% (11 of 364) among twins and 3.6% (13 of 360) among singletons (P = 0.66). The prevalence of fasting blood glucose (F-glucose) ≥5.6 mmol/L was 34.9% (127 of 364) for twins versus 24.7% (89 of 360) for singletons (P = 0.003). Median homeostasis model assessment-insulin resistance did not differ (P = 0.34).The MS and DM prevalences among young individuals in Guinea-Bissau were low. Twins did not have a higher MS and DM burden than singletons, though elevated F-glucose was more common among twins.
IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF detected by ELISA in rheumatoid arthritis.
Authors: M Gioud-Paquet, M Auvinet, T Raffin, P Girard, M Bouvier, E Lejeune, J C Monier
Journal: Annals of the Rheumatic Diseases (1987)

One hundred patients with rheumatoid arthritis (RA), of whom 73 were seropositive by latex or Waaler-Rose (WR) assays, or both, 100 healthy subjects, and 102 diseased controls (22 patients with systemic lupus erythematosus (SLE) and 80 with bronchial asthma) were evaluated for the presence of IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF by an enzyme linked immunosorbent assay (ELISA). Ninety two per cent, 65%, 68%, and 66% of the patients with RA were found to be positive for IgM, IgA, IgE, and IgG respectively. A positive correlation existed between the levels of IgM RF and IgA RF on the one hand and disease activity on the other, and the levels of IgM RF and IgA RF correlated with the levels of circulating immune complexes as measured by a C1q binding assay. The presence of extra-articular features also correlated positively with the levels of IgA RF and IgE RF. Five out of six patients with Sjögren's syndrome had very high levels of IgA RF. Of 47 patients typed for HLA-DR, DR1 and DR2 were significantly more frequent in those with the highest levels of IgM RF. Conversely, DR3 was associated with low levels or absence of IgA RF and IgE RF. These results suggest that immune response genes may regulate the level of different RF isotypes. The frequencies of IgM, IgA, IgE, and IgG RF were 59%, 36%, 9%, and 27% respectively in SLE and 25%, 2.5%, 70%, and 59% in bronchial asthma.
Regulation of blood-brain barrier endothelial cells by nitric oxide.
Authors: D Janigro, G A West, T S Nguyen, H R Winn
Journal: Circulation Research (1994)

Nitric oxide (NO) synthesized by vascular endothelial cells is a potent vasodilator substance. The actions of NO extend well beyond its vasodilatory properties, and increasingly, NO has been recognized as an important signal for intercellular and intracellular communication. Recently, NO has been implicated in the regulation of vascular and blood-brain barrier permeability. NO has also been shown to modulate ion channels in excitable cells, thus affecting neuronal firing. We report the results of patch-clamp experiments that show a modulatory action of NO as well as cGMP and cAMP on a hyperpolarization-activated current (Iha) carried by both Na+ and K+ ions in blood-brain barrier endothelial cells. Iha was recorded in cells dialyzed with 0.2 mmol/L GTP-gamma-S to inhibit a large inwardly rectifying potassium current. This ionic current and its modulation by NO may play a role in the regulation of the transport of ions, nutrients, and other molecules to the brain and serve as an integral part of the blood-brain barrier. The modulation of Iha by a cyclic guanosine nucleotide may also explain previous reports suggesting a role for NO in the regulation of blood-brain barrier function.
Tissue structure modification in knee osteoarthritis by use of joint distraction: an open 1-year pilot study
Authors: F. Intema, P. M. Van Roermund, A. C. A. Marijnissen, S. Cotofana, F. Eckstein, R. M. Castelein, J. W. J. Bijlsma, S. C. Mastbergen, F. P. J. G. Lafeber
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Modification of joint tissue damage is challenging in late-stage osteoarthritis (OA). Few options are available for treating end-stage knee OA other than joint replacement. <h3>Objectives</h3> To examine whether joint distraction can effectively modify knee joint tissue damage and has the potential to delay prosthesis surgery. <h3>Methods</h3> 20 patients (&lt;60 years) with tibiofemoral OA were treated surgically using joint distraction. Distraction (∼5 mm) was applied for 2 months using an external fixation frame. Tissue structure modification at 1 year of follow-up was evaluated radiographically (joint space width (JSW)), by MRI (segmentation of cartilage morphology) and by biochemical markers of collagen type II turnover, with operators blinded to time points. Clinical improvement was evaluated by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analogue Scale (VAS) pain score. <h3>Results</h3> Radiography demonstrated an increase in mean and minimum JSW (2.7 to 3.6 mm and 1.0 to 1.9 mm; p&lt;0.05 and &lt;0.01). MRI revealed an increase in cartilage thickness (2.4 to 3.0 mm; p&lt;0.001) and a decrease of denuded bone areas (22% to 5%; p&lt;0.001). Collagen type II levels showed a trend towards increased synthesis (+103%; p&lt;0.06) and decreased breakdown (−11%; p&lt;0.08). The WOMAC index increased from 45 to 77 points, and VAS pain decreased from 73 to 31 mm (both p&lt;0.001). <h3>Conclusions</h3> Joint distraction can induce tissue structure modification in knee OA and could result in clinical benefit. No current treatment is able to induce such changes. Larger, longer and randomised studies on joint distraction are warranted.
Expression of CD74 is increased in neurofibrillary tangles in Alzheimer's disease
Authors: Kathryn J Bryan, Xiongwei Zhu, Peggy L Harris, George Perry, Rudy J Castellani, Mark A Smith, Gemma Casadesus
Journal: Molecular Neurodegeneration (2008)

Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by progressive memory loss. Pathological markers of AD include neurofibrillary tangles, accumulation of amyloid-beta plaques, neuronal loss, and inflammation. The exact events that lead to the neuronal dysfunction and loss are not completely understood. However, pro-inflammatory cytokines, such as interleukin-1beta, interleukin-6, and tumor necrosis factor alpha, are increased in AD, along with gene expression of major histocompatibility complex (MHC) class II molecules and macrophage migration inhibitory factor (MIF). MHC class II molecules are found in microglia of the brain, while MIF is found in both microglia and neurons of the hypothalamus, hippocampus, and cortex. MIF is not only a lymphocyte mediator but also a pituitary factor with endocrine properties and can mediate phosphorylation of the extracellular signal-regulated kinase-1/2 MAP kinases pathway. In this study, we looked at CD74, an integral membrane protein that acts as both a chaperone for MHC class II molecules as well as a receptor binding site for MIF. CD74 was recently found to be increased in microglia in AD cases compared to age-matched controls, but has not been reported in neurons. In our analysis, immunohistochemistry revealed a significant increase in CD74 primarily in neurofibrillary tangles, amyloid-beta plaques, and microglia. This is the first finding to our knowledge that CD74 is increased in neurons of AD cases compared to age-matched control cases.
The twenty-krone piece
Authors: F. Treves
Journal: BMJ (2001)

Monetary endeavour is not considered proper for doctors. They are expected to set examples of noble mindedness, and therefore money should not be the key element from which they derive confidence, strength, and motivation. All physicians who have had grateful patients will agree that nothing is more fulfilling than sincere gratitude and an appreciation for making some contribution, however small, to the satisfactory outcome of an illness. Every one of us would also agree that such human qualities cannot possibly be replaced by money. But money can sometimes be important. In his reminiscences, Sir Frederick Treves, an outstanding London surgeon from around the turn of the 20th century, tells the following remarkable story, which we ought to keep in mind whenever we consider enduring values within our profession.1 

More than once in speaking at public meetings on behalf of hospitals I have alluded to my much valued possession—a twenty-krone piece—and have employed it as an illustration of the gratitude of the hospital patient.

The subject of this incident was a Norwegian sailor about fifty years of age, a tall, good-featured man with the blue eyes of his country and a face tanned by sun and by salt winds to the colour of weathered oak. His hair and his beard were grey, which made him look older than he was. He had been serving for three years as an ordinary seaman on an English sailing ship and spoke English perfectly. During …
Tumor suppressor PTEN affects tau phosphorylation: deficiency in the phosphatase activity of PTEN increases aggregation of an FTDP-17 mutant Tau.
Authors: Xue Zhang, Yun-wu Zhang, Shijie Liu, Ayelen Bulloj, Gary G Tong, Zhuohua Zhang, Francesca-Fang Liao, Huaxi Xu
Journal: Molecular Neurodegeneration (2006)

Aberrant hyperphosphorylation of tau protein has been implicated in a variety of neurodegenerative disorders. Although a number of protein kinases have been shown to phosphorylate tau in vitro and in vivo, the molecular mechanisms by which tau phosphorylation is regulated pathophysiologically are largely unknown. Recently, a growing body of evidence suggests a link between tau phosphorylation and PI3K signaling. In this study, phosphorylation, aggregation and binding to the microtubule of a mutant frontal temporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) tau in the presence of tumor suppressor PTEN, a major regulatory component in PI3K signaling, were investigated.Phosphorylation of the human mutant FTDP-17 tau, T40RW, was evaluated using different phospho-tau specific antibodies in the presence of human wild-type or phosphatase activity null mutant PTEN. Among the evaluated phosphorylation sites, the levels of Ser214 and Thr212 phospho-tau proteins were significantly decreased in the presence of wild-type PTEN, and significantly increased when the phosphatase activity null mutant PTEN was ectopically expressed. Fractionation of the mutant tau transfected cells revealed a significantly increased level of soluble tau in cytosol when wild-type PTEN was expressed, and an elevated level of SDS-soluble tau aggregates in the presence of the mutant PTEN. In addition, the filter/trap assays detected more SDS-insoluble mutant tau aggregates in the cells overexpressing the mutant PTEN compared to those in the cells overexpressing wild-type PTEN and control DNA. This notion was confirmed by the immunocytochemical experiment which demonstrated that the overexpression of the phosphatase activity null mutant PTEN caused the mutant tau to form aggregates in the COS-7 cells.Tumor suppressor PTEN can alleviate the phosphorylation of the mutant FTDP-17 tau at specific sites, and the phosphatase activity null PTEN increases the mutant tau phosphorylation at these sites. The changes of the tau phosphorylation status by ectopic expression of PTEN correlate to the alteration of the mutant tau's cellular distribution. In addition, the overexpression of the mutant PTEN can increase the level of the mutant tau aggregates and lead to the formation of visible aggregates in the cells.