tbuckley/cabot-search huggingface dataset:
Lactation intensity and fasting plasma lipids, lipoproteins, non-esterified free fatty acids, leptin and adiponectin in postpartum women with recent gestational diabetes mellitus: The SWIFT cohort
Authors: Erica P. Gunderson, Catherine Kim, Charles P. Quesenberry, Santica Marcovina, David Walton, Robert A. Azevedo, Gary Fox, Cathie Elmasian, Stephen Young, Nora Salvador, Michael Lum, Yvonne Crites, Joan C. Lo, Xian Ning, Kathryn G. Dewey
Journal: Metabolism (2014)
Diabetes mellitus attenuates the repolarization reserve in mammalian heart
Authors: C LENGYEL, L VIRAG, T BIRO, N JOST, J MAGYAR, P BILICZKI, E KOCSIS, R SKOUMAL, P NANASI, M TOTH
Journal: Cardiovascular Research (2006)

In diabetes mellitus several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models changes in these parameters were reported, but no such data are available in other mammalian species including the dog. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and its underlying transmembrane ionic currents and channel proteins in canine hearts.Diabetes was induced by a single injection of alloxan, a subgroup of dogs received insulin substitution. After the development of diabetes (8 weeks) electrophysiological studies were performed using conventional microelectrodes, whole cell voltage clamp, and ECG. Expression of ion channel proteins was evaluated by Western blotting. The QTc interval and the ventricular action potential duration in diabetic dogs were moderately prolonged. This was accompanied by significant reduction in the density of the transient outward K+ current (I(to)) and the slow delayed rectifier K+ current (I(Ks)), to 54.6% and 69.3% of control, respectively. No differences were observed in the density of the inward rectifier K+ current (I(K1)), rapid delayed rectifier K+ current (I(Kr)), and L-type Ca2+ current (I(Ca)). Western blot analysis revealed a reduced expression of Kv4.3 and MinK (to 25+/-21% and 48+/-15% of control, respectively) in diabetic dogs, while other channel proteins were unchanged (HERG, MiRP1, alpha(1c)) or increased (Kv1.4, KChIP2, KvLQT1). Insulin substitution fully prevented the diabetes-induced changes in I(Ks), KvLQT1 and MinK, however, the changes in I(to), Kv4.3, and Kv1.4 were only partially diminished by insulin.It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization, attenuates the repolarization reserve by decreasing I(to) and I(Ks) currents, and thereby may markedly enhance the risk of sudden cardiac death.
The use of the Dermatology Life Quality Index in patients with malignant carcinoid syndrome
Authors: H.K. Bell, A.L. Duncan
Journal: British Journal of Dermatology (2011)

Journal Article The use of the Dermatology Life Quality Index in patients with malignant carcinoid syndrome Get access H.K. Bell, H.K. Bell Department of Dermatology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool L14 3LB, U.K. *Department of Dermatology, Royal Preston Hospital, Preston PR2 9HT, U.K. E‐mail: hazel.bell@rlbuht.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar A.L. Duncan A.L. Duncan Department of Dermatology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool L14 3LB, U.K. *Department of Dermatology, Royal Preston Hospital, Preston PR2 9HT, U.K. E‐mail: hazel.bell@rlbuht.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue 2, 1 February 2012, Page 460, https://doi.org/10.1111/j.1365-2133.2011.10617.x Published: 01 February 2012
GENETICS OF COLON CANCER: Impact of Inheritance on Colon Cancer Risk
Authors: Randall W. Burt, M.D, James A. DiSario, M.D, Lisa Cannon-Albright, Ph.D
Journal: Annual Review of Medicine (1995)

▪ Abstract The genes that are mutated in two of the rare syndromes of hereditary colon cancer were recently identified, and genetic diagnosis is already possible in some cases. Acquired mutations of these same genes also appear to be important in sporadic colon cancers. Familial clustering of sporadic cases is common and may likewise arise from inherited susceptibility. Screening strategies for both the rare syndromes and the common cases of colon cancer with familial risk have been suggested. Certain clinical features allow stratification of colon cancer risk among common cases. It is anticipated that continued genetic investigation will result in more precise screening and improved diagnostic and therapeutic options for colon cancer.
Proteolysis of EphA2 Converts It from a Tumor Suppressor to an Oncoprotein
Authors: Naohiko Koshikawa, Daisuke Hoshino, Hiroaki Taniguchi, Tomoko Minegishi, Taizo Tomari, Sung-Ouk Nam, Mikiko Aoki, Takayuki Sueta, Takashi Nakagawa, Shingo Miyamoto, Kazuki Nabeshima, Alissa M. Weaver, Motoharu Seiki
Journal: Cancer Research (2015)

Abstract Eph receptor tyrosine kinases are considered candidate therapeutic targets in cancer, but they can exert opposing effects on cell growth. In the presence of its ligands, Eph receptor EphA2 suppresses signaling by other growth factor receptors, including ErbB, whereas ligand-independent activation of EphA2 augments ErbB signaling. To deploy EphA2-targeting drugs effectively in tumors, the anti-oncogenic ligand-dependent activation state of EphA2 must be discriminated from its oncogenic ligand-independent state. Because the molecular basis for the latter is little understood, we investigated how the activation state of EphA2 can be switched in tumor tissue. We found that ligand-binding domain of EphA2 is cleaved frequently by the membrane metalloproteinase MT1-MMP, a powerful modulator of the pericellular environment in tumor cells. EphA2 immunostaining revealed a significant loss of the N-terminal portion of EphA2 in areas of tumor tissue that expressed MT1-MMP. Moreover, EphA2 phosphorylation patterns that signify ligand-independent activation were observed specifically in these areas of tumor tissue. Mechanistic experiments revealed that processing of EphA2 by MT1-MMP promoted ErbB signaling, anchorage-independent growth, and cell migration. Conversely, expression of a proteolysis-resistant mutant of EphA2 prevented tumorigenesis and metastasis of human tumor xenografts in mice. Overall, our results showed how the proteolytic state of EphA2 in tumors determines its effector function and influences its status as a candidate biomarker for targeted therapy. Cancer Res; 75(16); 3327–39. ©2015 AACR.
The major allergen content of allergenic preparations reflects their biological activity
Authors: S. Dreborg, R. Einarsson
Journal: Allergy (1992)

The content of major allergens in biologically standardized allergenic preparations of birch, mite (Der p) , cat, Alternaria (Alt a) and ragweed (Amb e) was determined. It was found fairly constant between species , i.e. varied within a factor of 2, with the exception of Alt a 1 in Alternaria alternata extract. This variation is allowed by authorities between different batches prepared from the same species of allergen. The method for biological standardization (BS) prescribed in the Nordic Guidelines has, for common inhalant allergens, been shown to give reproducible results between regions of Europe. However, it is difficult to define patients suitable for BS of most food allergens as well as less common inhalant allergens. Therefore we propose that, in the future, BS is replaced by determination of well‐established major allergens and that 1 ng of major allergen is given the value of 1 Biological Unit. Clinical aspects Clinicians have had difficulties in understanding differences and similarities between units used by manufacturers for labelling of allergenic extracts. Biological standardization is time‐consuming and expensive. Probably therefore, and to avoid comparison with extracts prepared by other manufacturers, most manufacturers have used their own units and few of them have used the biological units as defined by the Nordic Guidelines or FDA. Determination of the amount of major allergen by ELISA is simple and cheap. However, the biological relevance of major allergen content has not been established. Our results clearly indicate the possibility of replacing biological units by major allergen content, provided the composition of allergens is adequate. The major allergen content can easily be declared by all manufacturers. In the future, manufacturers should be forced to declare the major allergen content, thus making it easier for clinicians to compare extracts from different suppliers.
The putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2
Authors: Fang Zheng, Yi-Ji Liao, Mu-Yan Cai, Yan-Hui Liu, Tian-Hao Liu, Shu-Peng Chen, Xiu-Wu Bian, Xin-Yuan Guan, Marie C Lin, Yi-Xin Zeng, Hsiang-Fu Kung, Dan Xie
Journal: Gut (2011)

<h3>Background</h3> Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-124) in hepatocellular carcinoma (HCC). <h3>Objective</h3> To determine the status of miR-124 expression and its underlying mechanisms in the pathogenesis of HCC. <h3>Methods</h3> The expression levels of miR-124 were first examined in HCC cell lines and tumour tissues by real-time PCR. The in vitro and in vivo functional effect of miR-124 was examined further. A luciferase reporter assay was conducted to confirm target associations. <h3>Results</h3> The expression levels of miR-124 were frequently reduced in HCC cells and tissues, and low-level expression of miR-124 was significantly associated with a more aggressive and/or poor prognostic phenotype of patients with HCC (p&lt;0.05). In HCC cell lines, stable overexpression of miR-124 was sufficient to inhibit cell motility and invasion in vitro, and suppress intrahepatic and pulmonary metastasis in vivo. In addition, ectopic overexpression of miR-124 in HCC cells inhibited epithelial–mesenchymal cell transition, formation of stress fibres, filopodia and lamellipodia. Further studies showed that miR-124 could directly target the 3<sup>′</sup>-untranslated region (3′-UTR) of both ROCK2 and EZH2 mRNAs, and suppress their mRNA and protein expressions. These findings suggest that miR-124 plays a critical role in regulating cytoskeletal events and epithelial–mesenchymal cell transition and, ultimately, inhibits the invasive and/or metastatic potential of HCC, probably by its direct target on ROCK2 and EZH2 genes. These results provide functional and mechanistic links between the tumour suppressor miRNA-124 and the two oncogenes ROCK2 and EZH2 on the aggressive nature of HCC. <h3>Conclusion</h3> These data highlight an important role for miR-124 in the regulation of invasion and metastasis in the molecular aetiology of HCC, and suggest a potential application of miR-124 in prognosis prediction and cancer treatment.
Secretion of immunoglobulins and plasma proteins from the jejunal mucosa. Transport rate and origin of polymeric immunoglobulin A.
Authors: P P Jonard, J C Rambaud, C Dive, J P Vaerman, A Galian, D L Delacroix
Journal: Journal of Clinical Investigation (1984)

Parameters of secretion of IgA and several other plasma proteins from the jejunal mucosa were investigated in 11 individuals who had a normal distribution of Ig-containing cells in the lamina propria and in one patient who was totally deficient in jejunal IgA and IgM plasmacytes. Jejunal samples were collected during segmental gut perfusion. The following results were obtained: (a) The secretion of polymeric IgA (p-IgA, mean equals 217 micrograms/40 cm per min) exceeded those of albumin (132 micrograms), IgG (35 micrograms), and monomeric IgA (m-IgA, 15 micrograms, or 6.4% of total IgA). About 35% of IgA was IgA2 in the jejunal secretion, compared with approximately 23% in serum. This closely corresponds to the 35 and 24% of IgA2 plasmocytes in jejunal mucosa and peripheral lymph nodes, respectively. (b) For each protein, a relative coefficient of excretion (RCE) was calculated (jejunum to serum concentration ratio expressed relative to that of albumin). RCEs of 1.41 for orosomucoid, 1.0 for albumin, 0.83 for IgG, and 0.74 for IgE and, in the deficient patient, of 0.64 for m-IgA and 0.016 for IgM were obtained. This was inversely related to the molecular weight of these proteins and indicated their predominantly passive transport into the jejunum. However, in normal individuals, the RCE of transferrin (approximately 1.11 greater than 1, P greater than 0.05), alpha 2-macro globulin (approximately 0.77), m-IgA (approximately 1.98), and p-IgA (approximately 218) exceeded the value expected from simple seepage from plasma, thus pointing to an additional role of either local gut synthesis and/or active transepithelial transport. (c) Approximately 98% of p-IgA, approximately 99% of IgM, and approximately 68% of m-IgA in jejunal secretions were derived from local production in the gut wall, as determined by 125I-p-IgA specific activities and/or by comparison between the RCE values of the deficient patient to the values of controls. Therefore, the jejunal production of p-IgA (approximately 312 mg/d per 40 cm vs. approximately 54 mg/d from bile) contributes the majority of upper intestinal IgA in humans. The active transport of plasma p-IgA across the intestinal mucosa (approximately 0.08 mg/40 cm per kg per d) contributes less than 2% of the total amount of p-IgA (4.5 mg/kg per d) that is cleared daily from plasma.
Enhanced gene transfer to arthritic joints using adeno-associated virus type 5: implications for intra-articular gene therapy
Authors: Janik Adriaansen, Sander W Tas, Paul L Klarenbeek, Andrew C Bakker, Florence Apparailly, Gary S Firestein, Christian Jorgensen, Margriet Jbm Vervoordeldonk, Paul Peter Tak
Journal: Annals of the Rheumatic Diseases (2005)

Gene therapy of the joint has great potential as a new therapeutic approach for the treatment of rheumatoid arthritis (RA). The vector chosen is of crucial importance for clinical success.To investigate the tropism and transduction efficiency in arthritic joints in vivo, and in synovial cells in vitro, using five different serotypes of recombinant adeno-associated virus (rAAV) encoding beta-galactosidase or green fluorescent protein genes.rAAV was injected into the ankle joints of rats with adjuvant arthritis after the onset of disease. Synovial tissue was examined at different time points for beta-galactosidase protein and gene expression by in situ staining and polymerase chain reaction (PCR) analysis, respectively. In addition, the ability of rAAV to transduce primary human fibroblast-like synoviocytes from patients with RA was investigated in vitro.Intra-articular injection of the rAAV5 serotype resulted in the highest synovial transduction, followed by much lower expression using rAAV2. Expression of the transgene was already detectable 7 days after injection and lasted for at least 4 weeks. Only background staining was seen for serotypes 1, 3, and 4. Importantly, there was a minimal humoral immune response to rAAV5 compared with rAAV2. Additionally, it was found that both rAAV2 and rAAV5 can efficiently transduce human fibroblast-like synoviocytes obtained from patients with RA.Intra-articular rAAV mediated gene therapy in RA might be improved by using rAAV5 rather than other serotypes.
THE LIFE CYCLE OF ANTIBODY-FORMING CELLS
Authors: Walter J. K. Tannenberg, Anand N. Malaviya
Journal: The Journal of Experimental Medicine (1968)

The generation, time of cells synthesizing 19S antibody was measured during the exponential phase of the primary and secondary immune responses. Using a plaque-forming cell assay together with a double label isotope method, the duration of the generation time was found to be about 13 hr, that of the S period was about 8 hr, and that of G-1 and G-2 were about 3 and 2 hr, respectively, in both immune responses. Previous work was confirmed showing that all plaque-forming cells observed during the exponential phase of the immune responses incorporate labeled thymidine, and therefore take part in proliferation. These results were obtained at points during both responses when the doubling time of the PFC was observed to be 6-7 hr. This finding makes untenable the hypothesis that the rate of appearance of PFC equals the rate of proliferation of these cells. A hypothesis is presented to account for these findings and to serve as a basis for further experiments.
Changes in hip and ankle range of motion and hip muscle strength in 8–11 year old novice female ballet dancers and controls: a 12 month follow up study
Authors: K L Bennell, K M Khan, B L Matthews, C Singleton
Journal: British Journal of Sports Medicine (2001)

Objectives —To evaluate in a 12 month longitudinal study changes in hip and ankle range of motion and hip muscle strength in young female novice ballet dancers. Methods —Fifty three of the original 77 (69%) female dancers aged 8–11 years and 40 of the original 49 (82%) controls returned for follow up measurements one year later. Supine right active hip external (ER) and internal (IR) rotation were measured using an inclinometer. A turnout protractor was used to assess standing active turnout range. Range of right weight bearing ankle dorsiflexion and calf muscle length were measured in a standing lunge position using an inclinometer. A manual muscle tester was used to assess right hip flexor, IR, ER, abductor and adductor strength. Results —The mean (SD) 12 month change in hip ER did not differ between dancers (11.7 (11.3)°) and controls (8.1 (17.6)°). Dancers gained 12.5 (13.5)° hip IR which was significantly greater than controls (0.5 (13.9)°). Greater IR change was associated with improved IR strength ( r = 0.34, p&lt;0.001). Dancers increased total turnout (12.0 (16.7)°) significantly more than controls (2.2 (20.0)°). There was no significant change in ankle dorsiflexion range in either group. Dancers and controls increased in all measures of hip muscle strength (p&lt;0.001) and dancers achieved significantly greater gains in three out of five muscle groups (all, p&lt;0.05). Conclusions —Total hip range of motion increased in both ballet students and controls at this young age. However, ankle dorsiflexion did not, which is probably due to this movement being blocked by bony apposition, rather than soft tissue stretch. This has implications for ballet teachers, as it has long been accepted that this movement could be improved with training. Dancers had greater increases in hip strength after 12 months compared with controls in muscles specific for ballet, suggesting that hip strength can be trained at this young age. Whether these gains are permanent requires further study.
Host immune response to<i>Chlamydia pneumoniae</i>heat shock protein 60 is associated with asthma
Authors: T. Huittinen, D. Hahn, T. Anttila, E. Wahlström, P. Saikku, M. Leinonen
Journal: European Respiratory Journal (2001)

Chlamydia pneumoniae infection has been associated with asthma. It has also been suggested that heat shock protein 60 (Hsp60) belonging to a class of highly conserved proteins may play a role in the pathogenesis of chlamydial infections. The purpose was to study whether the host immune response to C. pneumoniae Hsp60 is associated with asthma and decreased pulmonary function. An enzyme immunoassay was used to measure immunoglobulin-(Ig)A and IgG antibodies against recombinant C. pneumoniae Hsp60 and human Hsp60 in a study group consisting of 24 cases of recently symptomatic asthma and 62 nonasthmatic controls. A strong (r=0.50) and significant (p&lt;0.001) correlation was observed between C. pneumoniae and human Hsp60 IgA antibodies, but only C. pneumoniae Hsp60 IgA antibodies were significantly associated with asthma (p=0.02). Pulmonary function, as measured by forced expiratory volume in one second, also inversely correlated (r=−0.23, p=0.04) with the quantity of C. pneumoniae Hsp60 IgA antibodies, suggesting an association with the severity of pulmonary obstruction. By showing an association of Chlamydia pneumoniae heat shock protein 60 immunoglobulin A antibodies with asthma, the results support the hypothesis of an association between Chlamydia pneumoniae infection and asthma and support the need for further investigations on the role of heat shock protein 60 in the pathogenesis of asthma.
Myocardial Gene Expression of Regulators of Myocyte Apoptosis and Myocyte Calcium Homeostasis During Hemodynamic Unloading by Ventricular Assist Devices in Patients With End-Stage Heart Failure
Authors: B. Bartling, H. Milting, H. Schumann, D. Darmer, L. Arusoglu, M. M. Koerner, A. El-Banayosy, R. Koerfer, J. Holtz, H.-R. Zerkowski
Journal: Circulation (1999)

In patients with end-stage heart failure, characterized by an increased susceptibility to cardiomyocyte apoptosis and a labile cardiomyocyte calcium homeostasis, a ventricular assist device (VAD) is implanted for bridging to cardiac transplantation and results in myocardial unloading. Although phenotype changes in the failing heart are assumed to result from hemodynamic overload, the reversibility of these changes under unloading is unknown.By use of quantitative reverse-transcription polymerase chain reaction, mRNA expression analyses were performed on left ventricular specimens obtained from 10 nonfailing donor hearts (from 8 patients with dilated cardiomyopathy and 2 patients with coronary heart disease) at the time of VAD implantation and 36 to 169 days later during VAD removal with subsequent cardiac transplantation. In terminally failing hearts before VAD support, left ventricular mRNA analyses revealed increased Pro-ANP, reduced antiapoptotic Bcl-x(L) and antiapoptotic Fas isoform FasExo6Del, and a decreased ratio of sarcoplasmic reticulum Ca(2+)-ATPase per sarcolemmal Na(+)-Ca(2+) exchanger in comparison with nonfailing ventricles. After VAD unloading, ventricular transcription of Pro-ANP was immediately normalized, and apoptotic DNA fragmentation was attenuated. In patients with dilated cardiomyopathy, mRNAs of Bcl-x(L) and FasExo6Del/Fas were enhanced depending on time on VAD. The Bcl-x(L) mRNA level correlated positively with that of the Bcl-x(L) protein. Transcription of sarcoplasmic reticulum Ca(2+)-ATPase/Na(+)-Ca(2+) exchanger demonstrated recovery in only 4 of 10 patients.Mechanical support of the failing heart induces a time-dependent change in myocardial gene expression compatible with a decreased susceptibility to apoptosis.
Cadherin-11 Increases Migration and Invasion of Prostate Cancer Cells and Enhances their Interaction with Osteoblasts
Authors: Chih-Fen Huang, Cristina Lira, Khoi Chu, Mehmet Asim Bilen, Yu-Chen Lee, Xiangcang Ye, Soo Mi Kim, Angelica Ortiz, Fe-Lin Lin Wu, Christopher J. Logothetis, Li-Yuan Yu-Lee, Sue-Hwa Lin
Journal: Cancer Research (2010)

Cell adhesion molecules have been implicated in the colonization of cancer cells to distant organs. Prostate cancer (PCa) has a propensity to metastasize to bone, and cadherin-11, which is an osteoblast cadherin aberrantly expressed in PCa cells derived from bone metastases, has been shown to play a role in the metastasis of PCa cells to bone. However, the mechanism by which cadherin-11 is involved in this process is not known. Here, we show that expression of cadherin-11 in cadherin-11-negative C4-2B4 cells increases their spreading and intercalation into an osteoblast layer and also stimulates C4-2B4 cell migration and invasiveness. The downregulation of cadherin-11 in cadherin-11-expressing metastatic PC3 cells decreases cell motility and invasiveness. Further, both the juxtamembrane (JMD) and beta-catenin binding domains (CBS) in the cytoplasmic tail of cadherin-11 are required for cell migration and invasion, but not spreading. Gene array analyses showed that several invasion-related genes, including MMP-7 and MMP-15, are upregulated in cadherin-11-expressing, but not in cad11-DeltaJMD-expressing or cad11-DeltaCBS-expressing, C4-2B4 cells. These observations suggest that cadherin-11 not only provides a physical link between PCa cells and osteoblasts but also increases PCa cell motility and invasiveness that may facilitate the metastatic colonization of PCa cells in bone.