tbuckley/cabot-search huggingface dataset:
Effects of a pharmacological dose of cholecystokinin on bile acid kinetics and biliary cholesterol saturation in man.
Authors: R P Jazrawi, T C Northfield
Journal: Gut (1986)

In order to study the mechanisms influencing bile acid pool size and cholesterol saturation index of fasting gall bladder bile, eight obese volunteers were placed on a low calorie diet for six weeks, and given intramuscular injections of a pharmacological dose of cholecystokinin octapeptide (CCK-OP, 5 micrograms) at mealtimes for half that period (alternating order). During CCK-OP administration, postprandial emptying of the gall bladder (mean +/- SEM) increased from 58 +/- 11% to 82 +/- 5% (p less than 0.005), and small intestinal transit time decreased from 205 +/- 27 to 178 +/- 26 minutes (NS). Bile acid pool size decreased from 4.6 +/- 0.3 to 3.1 +/- 0.3 mmol (p less than 0.001), while fractional turnover rate for chenodeoxycholic acid increased from 0.23 +/- 0.02 to 0.36 +/- 0.03 per day (p less than 0.005), suggesting an increase in recycling frequency of the pool. Synthesis rate was unchanged (0.43 +/- 0.08 vs 0.44 +/- 0.07 mmol/day), suggesting a new steady state. The cholesterol saturation index of fasting gall bladder bile increased in all subjects from 1.3 +/- 0.1 to 1.6 +/- 0.1 (p less than 0.005). Fasting gall bladder volume was reduced from 29 +/- 4 to 20 +/- 7 ml (p less than 0.01). Fractional turnover rate on the two regimens correlated with gall bladder emptying (n = 16, r = 0.61, p less than 0.01), but not with small intestinal transit time (r = 0.07, NS). Bile acid pool size correlated with fractional turnover rate (r = -0.73, p less than 0.005) and with cholesterol saturation index (r = -0.56, p less than 0.025). These findings suggest that CCK influences bile acid kinetics and cholesterol saturation index of fasting gall bladder in man; and that these effects of CCK are mainly mediated via alterations in gall bladder emptying rather than through alterations in small intestinal transit rate.
Evaluation of an ELISA system for determination of class-specific antibodies to native and denatured DNA in man.
Authors: G.M Halliday, M.R Salaman, M.H Seifert, K.J Johnson, A.D Malcolm
Journal: Annals of the Rheumatic Diseases (1985)

Enzyme-linked immunosorbent assays (ELISA) have been set up for determination of plasma IgG and IgM antibodies to native (n) and denatured (d) DNA. Normal male and female donors generally gave low values in the assays for IgG; IgM control values were higher, particularly in females. Mean values for patients with systemic lupus erythematosus (SLE) were greatly raised in all four categories of assay in relation to the control (female) group. Levels of IgG anti-nDNA in SLE correlated well with a standard diagnostic test (Farr), and this ELISA assay was more successful than Farr in discriminating between patients and normal females. No such correlation with Farr was found for IgM anti-nDNA. Correlations were found in SLE between levels of antibodies to nDNA and dDNA. Inhibition tests--including those with a plasmid DNA preparation containing no single-stranded regions--showed that most of the IgG antibodies determined in the 9native9 assay were able to bind to nDNA and dDNA with comparable avidity, whereas most of those reacting in the 9denatured9 assay could only bind dDNA. The former antibodies were probably directed against shared determinants on the deoxyribose-phosphate backbone and the latter against base-dependent structures not exposed in nDNA. Inhibition results for IgM assays were similar, though the predominance of antibodies specific for dDNA appeared less marked. ELISA assays could well prove more useful than established methods in diagnosis and monitoring of SLE and other diseases.
Genetics of Hemochromatosis
Authors: L.M. Cullen, BSc, G.J. Anderson, PhD, G.A. Ramm, PhD, E.C. Jazwinska, PhD, L.W. Powell, MD, PhD, DUniv, FRCP, FRACP, FRCPT
Journal: Annual Review of Medicine (1999)

Hereditary hemochromatosis (HHC) is a common autosomal recessive disorder of iron metabolism that results in progressive iron overload and can be fatal if untreated. The hemochromatosis gene (HFE) was identified by positional cloning in 1996. Two missense mutations have been described in HFE. The majority of HHC patients are homozygous for a cysteine-to-tyrosine substitution (C282Y); however, a small number are homozygous for a histidine-to-aspartic-acid substitution (H63D) or are heterozygous for both of these mutations. Mechanisms by which C282Y and H63D may disrupt the normal functioning of HFE have been suggested, but the role of HFE in the process of normal iron metabolism has yet to be clearly defined.
Interferon-gamma in the treatment of systemic sclerosis: a randomized controlled multicentre trial
Authors: None Grassegger, None Schuler, None Hessenberger, None Walder-Hantich, None Jabkowski, None Macheiner, None Salmhofer, None Zahel, None Pinter, None Herold, None Klein, None Fritsch
Journal: British Journal of Dermatology (1998)

We report the results of a randomized controlled multicentre study on interferon‐gamma (IFN‐γ) treatment of systemic sclerosis as determined by skin sclerosis, renal and other organ involvement, global assessment, subjective symptoms and quality of life. Forty‐four patients were enrolled into the trial, 27 in the treatment group and 17 in the control group. All patients presented with type I or type II scleroderma. Twenty‐nine patients (64%) finished the study. The mean duration of Raynaud's phenomenon and skin sclerosis was 15.3 and 10.8 years, respectively. The skin scores tended to improve in the treatment group (P > 0.05). Mouth aperture increased significantly from 38.5 to 47.7 mm in the treatment group (P < 0.001). Subanalysis of IFN‐γ treated patients with normalized skin sclerosis scores ≥1 showed significant improvement in both skin involvement and subjective symptoms (P < 0.05). Organ involvement improved in eight of 18 treatment patients and in three of 11 control patients. It worsened in three of 18 treatment patients and in four of 11 control patients. One control patient died due to cardiorespiratory failure during the study. No deterioration of renal function occurred during IFN‐γ treatment. There was a significant improvement in quality of life parameters in the control group but not in the treatment group. Plasma levels of neopterin increased significantly during IFN‐γ treatment but not in the control group, whereas N‐terminal procollagen III peptide levels did not change in either group. There was a high frequency of mild to moderate influenza‐like adverse events during IFN‐γ treatment. Only four of nine drop‐out patients, however, experienced symptoms most probably associated with IFN‐γ treatment. We conclude that IFN‐γ therapy has mild beneficial effects on skin sclerosis and disease‐associated symptoms in type I and II scleroderma. IFN‐γ treatment was associated with acceptable tolerability and did not induce major renal dysfunction in our patients.
A unique sequence of the NZW I-E beta chain and its possible contribution to autoimmunity in the (NZB x NZW)F1 mouse.
Authors: J Schiffenbauer, D M McCarthy, N R Nygard, S L Woulfe, D K Didier, B D Schwartz
Journal: The Journal of Experimental Medicine (1989)

The (NZB x NZW)F1 mouse strain develops a syndrome of accelerated autoimmunity including severe renal disease and early death. Evidence suggests that class II molecules play a central role in this process. Previous studies have suggested that the NZW strain contributes at least one gene to the development of accelerated autoimmunity that is linked to the H-2 complex, and antibodies to murine class II molecules have been used to ameliorate disease in (NZB x NZW)F1 mice. We therefore wished to sequence the class II molecules from NZW mice to identify any unique sequences that may contribute to disease development. We constructed oligonucleotide primers corresponding to the 5' and 3' regions of the second exon of class II genes from a variety of haplotypes, and used these primers in a polymerase chain reaction to sequence the second exon of the NZW I-A alpha, I-A beta, and I-E beta genes. We report that the second exons of NZW I-A alpha, I-A beta, and I-E alpha are identical to their counterparts of the previously sequenced u haplotype, and that the second exon of NZW I-E beta is identical to its counterpart from u except for a single base change that results in a substitution of arginine for threonine at amino acid 72. This base and amino acid are identical to those found at the same positions in the s haplotype.
Malignant Tumor Formation After Transplantation of Short-Term Cultured Bone Marrow Mesenchymal Stem Cells in Experimental Myocardial Infarction and Diabetic Neuropathy
Authors: Jin-Ok Jeong, Ji Woong Han, Jin-Man Kim, Hyun-Jai Cho, Changwon Park, Namho Lee, Dong-Wook Kim, Young-Sup Yoon
Journal: Circulation Research (2011)

Bone marrow (BM)-derived mesenchymal stem cells (MSCs) hold great promise for cardiovascular cell therapy owing to their multipotency and culture expandability.The aim of the study was to investigate whether MSCs can treat experimental acute myocardial infarction (MI) and diabetic neuropathy.We isolated mononuclear cells from mouse BM and cultured MSCs in a conventional manner. Flow cytometry analyses of these cultured cells at passage 4 showed expression of typical MSC markers such as CD44 and CD29, but not hematopoietic markers such as c-kit, flk1, and CD34. To determine the therapeutic effects of MSCs, we injected MSCs into the peri-infarct area after ligation of the left anterior descending coronary arteries of mice and, as separate experiments, injected the same batch of MSCs into hindlimb muscles of mice with diabetic neuropathy. During the follow-up at 4 to 8 weeks after cell transplantation, growing tumors were observed in 30% of hearts in the MI model, and in 46% of hindlimbs in the diabetic neuropathy model. Histological examination of the tumors revealed hypercelluarity, pleomorphic nucleoli, cytological atypia and necrosis, and positive staining for α-smooth muscle actin, indicative of malignant sarcoma with myogenic differentiation. Chromosomal analysis of these MSCs showed multiple chromosomal aberrations including fusion, fragmentation, and ring formation.Genetically unmodified MSCs can undergo chromosomal abnormalities even at early passages and form malignant tumors when transplanted in vivo. These results suggest that careful monitoring of chromosomal status is warranted when in vitro expanded MSCs are used for cell therapy such as for MI.
Dystrophin-glycoprotein complex and laminin colocalize to the sarcolemma and transverse tubules of cardiac muscle.
Authors: R Klietsch, J M Ervasti, W Arnold, K P Campbell, A O Jorgensen
Journal: Circulation Research (1993)

The expression and subcellular distribution of the dystrophin-glycoprotein complex and laminin were examined in cardiac muscle by immunoblot and immunofluorescence analysis of rabbit and sheep papillary muscle. The five dystrophin-associated proteins (DAPs), 156-DAG, 59-DAP, 50-DAG, 43-DAG, and 35-DAG, were identified in rabbit ventricular muscle and found to codistribute with dystrophin in both papillary myofibers and Purkinje fibers. The DAPs and dystrophin codistributed not only in the free surface sarcolemma but also in interior regions of the myofibers where T tubules are present. Neither the DAPs nor dystrophin were detected in intercalated discs, a specialized region of cardiac sarcolemma where neighboring myocardial cells are physically joined by cell-cell junctions. Similarly, in bundles of Purkinje fibers, which lack T tubules, DAPs and dystrophin were also found to codistribute at the free surface sarcolemma but were not detected either in the region of surface sarcolemma closely apposed to a neighboring Purkinje fiber or in interior regions of these myofibers. Comparison between the distribution of the dystrophin-glycoprotein complex and laminin showed that laminin codistributes with the components of this complex in both papillary myofibers and Purkinje fibers. These results are consistent with previous findings demonstrating that the extracellularly exposed 156-DAG (dystroglycan) of the skeletal muscle dystrophin-glycoprotein complex binds laminin, a component of the basement membrane. Although we demonstrate that DAPs, dystrophin, and laminin colocalize to the sarcolemma in rabbit and sheep papillary myofibers as they do in skeletal myofibers, the most striking difference between the subcellular distribution of these proteins in cardiac and skeletal muscle is that the dystrophin-glycoprotein complex and laminin also localize to regions of the fibers where T tubules are distributed in cardiac but not in skeletal muscle. These results imply that the protein composition and thus possibly some functions of T tubules in cardiac muscle are distinct from those of skeletal muscle.
Attitudes of United Kingdom rheumatologists to musculoskeletal ultrasound practice and training
Authors: J. Cunnington, P. Platt, G. Raftery, D. Kane
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> This study was performed to describe what clinical rheumatologists currently use musculoskeletal ultrasound (MSUS) for, how they are currently training and is the first study to survey rheumatologists to determine their preferences for MSUS training implementation. <h3>Methods:</h3> 250 questionnaires were distributed at the British Society of Rheumatology Annual General Meeting (BSR AGM), 2005. <h3>Results:</h3> 126 (50%) of questionnaires were completed by UK rheumatologists and were analysed. 117 (93%) of the respondents use MSUS imaging for patient management, with 41 (33%) indicating they perform MSUS themselves. Only two (2%) performed MSUS for &gt;5 years. Rheumatologists use MSUS to image all peripheral joints—particularly the hands and feet—to assess joint and soft tissue inflammation and to guide joint injections. Lack of training in MSUS was the principal reason for not performing MSUS. Respondents expressed a preference for future training to be via a programme of regular sessions, with training delivered by either consultant radiologists or rheumatologists. Mentoring was the educational tool and assessment method of choice. <h3>Conclusions:</h3> The majority of respondents use MSUS in the management of their patients, with a third performing MSUS themselves. The report indicates rheumatologists' preferences on how training should be delivered in the future.
Phase I/II study of capecitabine and vinorelbine in pretreated patients with metastatic breast cancer
Authors: A. Welt, G. von Minckwitz, C. Oberhoff, D. Borquez, R. Schleucher, S. Loibl, A. Harstrick, M. Kaufmann, S. Seeber, U. Vanhoefer
Journal: Annals of Oncology (2004)
Phylogenetic Analysis Based on Spectral Methods
Authors: Melanie Abeysundera, Chris Field, Hong Gu
Journal: Molecular Biology and Evolution (2011)

Whole-genome or multiple gene phylogenetic analysis is of interest since single gene analysis often results in poorly resolved trees. Here, the use of spectral techniques for analyzing multigene data sets is explored. The protein sequences are treated as categorical time series, and a measure of similarity between a pair of sequences, the spectral covariance, is based on the common periodicity between these two sequences. Unlike the other methods, the spectral covariance method focuses on the relationship between the sites of genetic sequences. By properly scaling the dissimilarity measures derived from different genes between a pair of species, we can use the mean of these scaled dissimilarity measures as a summary statistic to measure the taxonomic distances across multiple genes. The methods are applied to three different data sets, one noncontroversial and two with some dispute over the correct placement of the taxa in the tree. Trees are constructed using two distance-based methods, BIONJ and FITCH. A variation of block bootstrap sampling method is used for inference. The methods are able to recover all major clades in the corresponding reference trees with moderate to high bootstrap support. Through simulations, we show that the covariance-based methods effectively capture phylogenetic signal even when structural information is not fully retained. Comparisons of simulation results with the bootstrap permutation results indicate that the covariance-based methods are fairly robust under perturbations in sequence similarity but more sensitive to perturbations in structural similarity.
Divergence-Based Framework for Common Spatial Patterns Algorithms
Authors: Wojciech Samek, Motoaki Kawanabe, Klaus-Robert Muller
Journal: IEEE Reviews in Biomedical Engineering (2013)

Controlling a device with a brain-computer interface requires extraction of relevant and robust features from high-dimensional electroencephalographic recordings. Spatial filtering is a crucial step in this feature extraction process. This paper reviews algorithms for spatial filter computation and introduces a general framework for this task based on divergence maximization. We show that the popular common spatial patterns (CSP) algorithm can be formulated as a divergence maximization problem and computed within our framework. Our approach easily permits enforcing different invariances and utilizing information from other subjects; thus, it unifies many of the recently proposed CSP variants in a principled manner. Furthermore, it allows to design novel spatial filtering algorithms by incorporating regularization schemes into the optimization process or applying other divergences. We evaluate the proposed approach using three regularization schemes, investigate the advantages of beta divergence, and show that subject-independent feature spaces can be extracted by jointly optimizing the divergence problems of multiple users. We discuss the relations to several CSP variants and investigate the advantages and limitations of our approach with simulations. Finally, we provide experimental results on a dataset containing recordings from 80 subjects and interpret the obtained patterns from a neurophysiological perspective.
Antiviral Activity of Tumor Necrosis Factor (TNF) Is Mediated via p55 and p75 TNF Receptors
Authors: Janet Ruby, Horst Bluethmann, Jacques J. Peschon
Journal: The Journal of Experimental Medicine (1997)

The antiviral nature of tumor necrosis factor (TNF) is generally well accepted. TNF appears to induce multiple antiviral mechanisms, and to synergize with interferon (IFN)-γ in promoting antiviral activities. We infected TNF receptor (TNFR)-deficient mice with the virulent murine pathogen, ectromelia virus (EV), and observed that otherwise resistant mice were susceptible to lethal infection. To study the molecular basis of the antiviral action of TNF, mice were infected with a recombinant vaccinia virus encoding murine TNF (VV-HA-TNF). In normal mice, the replication of VV-HA-TNF was highly attenuated. In contrast, mice in which the TNFR type 1 (p55) or the TNFR type 2 (p75) were genetically disrupted showed a moderate defect in their capacity to clear the TNF-encoding virus. The contribution of both TNF receptors to the control of VV-HA-TNF was confirmed by the enhanced replication of VV-HA-TNF in mice deficient for both p55 and p75. These observations were corroborated by infecting TNFR-deficient mice with EV. For both infections, the p55 and p75 TNFRs were necessary to maintain normal levels of resistance. Thus, the antiviral activity of TNF is mediated via both TNFRs in vivo. Furthermore, these studies establish that TNF is an important component of the host response to a natural virus infection.
Ventilatory and heart rate responses to hypoxia and hypercapnia in patients with diabetes mellitus.
Authors: M Nishimura, K Miyamoto, A Suzuki, H Yamamoto, M Tsuji, F Kishi, Y Kawakami
Journal: Thorax (1989)

The ventilatory response to isocapnic progressive hypoxia and hyperoxic progressive hypercapnia in 24 diabetic patients were compared with those of sex and age matched normal control subjects. The heart rate response to hypoxia was also measured in both groups. In diabetic patients the ventilatory and heart rate responses to hypoxia were significantly lower than those in the control group (0.10 v 0.24 l/min/% fall/m2 and 0.5 l v 1.27 beats/min/% fall respectively). The ventilatory response to hypercapnia was significantly higher (1.09 v 0.76 l/min/mm Hg/m2) in the diabetic patients. There was a significant correlation between the hypoxic ventilatory response and the heart rate response in diabetic patients (r = 0.56), but not in the control group (r = 0.28). In addition, both the ventilatory and the heart rate responses to hypoxia in diabetic patients had weak but significant correlations with the heart rate variation during deep breathing. It is concluded that the ventilatory and heart rate responses to hypoxia in diabetic patients are impaired, whereas the ventilatory response to hypercapnia is well preserved.
Three diagnoses become one: a woman with ground-glass attenuation develops fever
Authors: E. J Hoorn, J. A van Laar, J. G den Hollander, J. M Kros, E. Brusse
Journal: Thorax (2010)

In 2002 a 73-year-old woman (non-smoking, medical history of allergic rhinitis) was referred to a rheumatologist because of synovitis of the metacarpophalangeal and proximal interphalangeal joints of both hands which had slowly developed over 3 months. Late-onset rheumatoid arthritis was suspected. Morning stiffness, rheumatoid nodules, erosions of cartilage or bone, rheumatoid factor and antibodies to cyclic citrullinated peptides were absent. Prednisone (2.5–5 mg daily) and non-steroidal anti-inflammatory drugs were started.

In 2004 she was referred …
Towards a better classification of erythrokeratodermias
Authors: D. Hohl
Journal: British Journal of Dermatology (2000)

Journal Article Towards a better classification of erythrokeratodermias Get access D. Hohl D. Hohl Dermatogenetic Unit and Laboratory for Cutaneous Biology, Department of Dermatology, University Hospital (CHUV/DHURDV), CH‐1011 Lausanne, Switzerland, Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 6, 1 December 2000, Pages 1133–1137, https://doi.org/10.1046/j.1365-2133.2000.04001.x Published: 01 December 2000
Assessment of patient-derived tumour xenografts (PDXs) as a discovery tool for cancer epigenomics
Authors: Paul Guilhamon, Lee M Butcher, Nadege Presneau, Gareth A Wilson, Andrew Feber, Dirk S Paul, Moritz Schütte, Johannes Haybaeck, Ulrich Keilholz, Jens Hoffman, Mark T Ross, Adrienne M Flanagan, Stephan Beck
Journal: Genome Medicine (2014)

The use of tumour xenografts is a well-established research tool in cancer genomics but has not yet been comprehensively evaluated for cancer epigenomics. In this study, we assessed the suitability of patient-derived tumour xenografts (PDXs) for methylome analysis using Infinium 450 K Beadchips and MeDIP-seq. Controlled for confounding host (mouse) sequences, comparison of primary PDXs and matching patient tumours in a rare (osteosarcoma) and common (colon) cancer revealed that an average 2.7% of the assayed CpG sites undergo major (Δβ ≥ 0.51) methylation changes in a cancer-specific manner as a result of the xenografting procedure. No significant subsequent methylation changes were observed after a second round of xenografting between primary and secondary PDXs. Based on computational simulation using publically available methylation data, we additionally show that future studies comparing two groups of PDXs should use 15 or more samples in each group to minimise the impact of xenografting-associated changes in methylation on comparison results. Our results from rare and common cancers indicate that PDXs are a suitable discovery tool for cancer epigenomics and we provide guidance on how to overcome the observed limitations.