tbuckley/cabot-search huggingface dataset:
Genetics of Transplacentally Induced Teratogenic and Carcinogenic Effects in Rabbits Treated With &lt;italic&gt;N&lt;/italic&gt;-Nitroso-&lt;italic&gt;N&lt;/italic&gt;-ethylurea&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: R R Fox, H Meier, H G Bedigian, D D Crary
Journal: JNCI Journal of the National Cancer Institute (1982)

Pregnant rabbits of three partially inbred strains, WH/J, IIIVO/J, and X/J, mated to either IIIVO/J or WH/J males were given ip injections of 60 mg of N-nitroso-N-ethylurea dissolved in trioclanoin on day 18 of gestation. Genetic differences in tumor susceptibility between strains WH/J (low-tumor-incidence strain) and IIIVO/J (high-tumor-incidence strain) have previously been demonstrated. Of 22 WH/J × IIIVO/J hybrid progeny weaned, 17 developed primary renal tumors at 5.0±0.5 (mean ± SE) months of age. Of 17 IIIVO/J × WH/J hybrid progeny weaned, 16 developed primary renal tumors at 4.0±0.7 months of age. Of 5 X/J × IIIVO/J hybrid progeny weaned, all developed primary renal tumors at 4.2±0.5 months of age. In addition, 8 metastatic nephroblastomas were observed, with the lung being the primary site of metastasis. Neurofibromas were observed in 12 per 22, 12 per 17, and 3 per 5 rabbits, respectively, from the various hybrid groups, many of which also had neurilemmal cysts. In addition, 1 hepatoma and 2 hemangiomas were observed. Also, teratogenic effects of disproportionate miniaturization including a left-right reduction in ear length were observed. Epidermoid cysts also formed and then regressed during the development of these treated animals. The following conclusions can be drawn from the data: The susceptibility to renal tumor and to neurofibroma induction appears to be inherited as a dominant characteristic. The disproportionate miniaturization is greatly dependent on the maternal genotype of the particular hybrid. The presence of this disproportionate miniaturization appears to be related to renal tumor induction. The epidermoid cysts, the renal tumor, and the neurofibromas all appear to be of independent etiologies.
From Genetic Risk Awareness to Overt Type 1 Diabetes
Authors: Eszter Goldstein, Robert Hermann, Timo J. Renfors, Kirsti M. Näntö-Salonen, Tapio Korhonen, Maarit Kärkkäinen, Riitta K. Veijola, Mikael Knip, Tuula T. Simell, Olli G. Simell
Journal: Diabetes Care (2009)

OBJECTIVE To evaluate the psychological burden of parents facing increasing risk of type 1 diabetes in their children. RESEARCH DESIGN AND METHODS In the population-based Type 1 Diabetes Prediction and Prevention (DIPP) Study, newborn infants with HLA-DQB1–conferred diabetes risk were enrolled in sequential analyses of diabetes-associated autoantibodies. Those persistently positive for at least two autoantibodies were recruited to a randomized double-blinded intervention trial. The experience of stress in parents of 664 children was measured using Parenting Stress Index self-report inventory. RESULTS While diagnosis of diabetes increased parental stress, the appearance of autoantibodies or participation in the intervention trial did not. Mothers had higher stress levels than fathers. Single parenthood and chronically ill family members increased parental stress. CONCLUSIONS Parental stress was not increased by notification of autoantibody positivity or by participation in an intervention trial. Other demanding family conditions contributed to the experience of stress.
M34 Actin Regulatory Protein Is a Sensitive Diagnostic Marker for Early- and Late-Stage Mammary Carcinomas
Authors: Zoraida Soriano, Joel D. Pardee
Journal: Clinical Cancer Research (2004)

Abstract Purpose: At present, there is no available molecular marker that reliably detects the earliest stages of epithelial transformation in the majority of patients affected with incipient breast carcinoma. Here we introduce M34 protein, a mammalian actin filament regulatory protein, as a highly sensitive and easily detected positive cellular marker for both early and late stages of breast carcinoma. Experimental Design: In this study, 24 human lactation duct neoplasms from postmenopausal women, including fibroadenoma, ductal carcinoma in situ, intraductal lobular papilloma, and metastatic adenocarcinoma, were analyzed for the presence of M34 protein by histochemical staining of paraffin and fresh-frozen sections. Results: All 24 neoplasias tested positive for M34, whereas none of the 4 normal breast tissues stained for the protein. M34 identification was strongly positive for transformed epithelium in all tumor types tested. Twelve precancerous lesions of fibroadenoma (n = 4), intraductal papilloma (n = 4), and incipient ductal carcinoma in situ (n = 4) all showed high levels of M34 staining, suggesting that precancerous tumors, as well as the earliest stages of mammary carcinoma, can be sensitively detected. Furthermore, anti-M34 antibody selectively stained all 12 advanced-stage metastatic adenocarcinoma cell masses and micrometastases in axillary lymph nodes tested. Single-cell micrometastases embedded in connective tissue or lymph node parenchyma could be clearly resolved by M34 with horseradish peroxidase staining. Lymphocytes, normal ductal endothelium, and vascular endothelial cells were M34-negative, as were muscle, nerve, and adipose tissues. Low-level M34 staining was detected in connective tissue fibroblasts, macrophages, and neutrophils. Conclusions: To our knowledge, no previously reported markers have shown high sensitivity of detection for both the earliest and most advanced stages of breast carcinoma. Consequently, M34 appears uniquely suited for diagnosis of the earliest stages of lactation duct transformation as well as for advanced-stage mammary carcinoma metastases in surgical margins and axillary lymph nodes.
Decreased serum insulin-like growth factor-I associated with growth failure in newborn lambs with experimental cyanotic heart disease.
Authors: D Bernstein, J R Jasper, R G Rosenfeld, R L Hintz
Journal: Journal of Clinical Investigation (1992)

To determine whether chronic hypoxemia results in alterations in endocrine function that may contribute to growth failure, we measured growth hormone (GH), somatomedins (insulin-like growth factors I and II, IGF-I and IGF-2), hepatic growth hormone receptors, and circulating IGF-binding proteins IGFBP-3 and IGFBP-2 in 12 newborn lambs with surgically created pulmonic stenosis and atrial septal defect, and in 10 controls. During chronic hypoxemia (oxygen saturation of 60-74% for 2 wk), weight gain was 60% of control (hypoxemic, 135 +/- 20 vs. control, 216 +/- 26 g/d, P less than 0.02). IGF-I was decreased by 43% (hypoxemic 253.6 +/- 29.3 SE vs. control 448.0 +/- 75.5 ng/ml, P = 0.01), whereas GH was unchanged (19.9 +/- 5.1 vs. 11.9 +/- 3.0 ng/ml, NS). The increase in IGF-1 was associated with a decrease in IGFBP-3 (hypoxemic, 5.09 +/- 1.25 vs. control, 11.2 +/- 1.08 arbitrary absorbency units per mm (Au.mm), P less than 0.01), and increase in IGFBP-2 (0.47 +/- 0.03 vs. 0.19 +/- 0.13 Au.mm, P less than 0.05), but no significant downregulation of hepatic GH receptors (hypoxemic, 106.1 +/- 20.1 vs. control, 147.3 +/- 25.9 fmol/mg, NS). Thus, chronic hypoxemia in the newborn is associated with a decrease in IGF-I and IGFBP-3 in the face of normal GH. This suggests peripheral GH unresponsiveness, similar to protein-calorie malnutrition or GH receptor deficiency dwarfism, but mediated at a level distal to the hepatic GH receptor.
IL-26 is overexpressed in chronically HCV-infected patients and enhances TRAIL-mediated cytotoxicity and interferon production by human NK cells
Authors: Charline Miot, Elodie Beaumont, Dorothée Duluc, Hélène Le Guillou-Guillemette, Laurence Preisser, Erwan Garo, Simon Blanchard, Isabelle Hubert Fouchard, Christophe Créminon, Patricia Lamourette, Isabelle Fremaux, Paul Calès, Françoise Lunel-Fabiani, Jérôme Boursier, Oliver Braum, Helmut Fickenscher, Philippe Roingeard, Yves Delneste, Pascale Jeannin
Journal: Gut (2014)

Interleukin-26 (IL-26) is a member of the IL-10 cytokine family, first discovered based on its peculiar expression by virus-transformed T cells. IL-26 is overexpressed in chronic inflammation (rheumatoid arthritis and Crohn's disease) and induces proinflammatory cytokines by myeloid cells and some epithelial cells. We thus investigated the expression and potential role of IL-26 in chronic HCV infection, a pathology associated with chronic inflammation.IL-26 was quantified in a cohort of chronically HCV-infected patients, naive of treatment and its expression in the liver biopsies investigated by immunohistochemistry. We also analysed the ability of IL-26 to modulate the activity of natural killer (NK) cells, which control HCV infection.The serum levels of IL-26 are enhanced in chronically HCV-infected patients, mainly in those with severe liver inflammation. Immunohistochemistry reveals an intense IL-26 staining in liver lesions, mainly in infiltrating CD3+ cells. We also show that NK cells from healthy subjects and from HCV-infected patients are sensitive to IL-26. IL-26 upregulates membrane tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) expression on CD16- CD56(bright) NK cells, enabling them to kill HCV-infected hepatoma cells, with the same efficacy as interferon (IFN)-α-treated NK cells. IL-26 also induces the expression of the antiviral cytokines IFN-β and IFN-γ, and of the proinflammatory cytokines IL-1β and TNF-α by NK cells.This study highlights IL-26 as a new player in the inflammatory and antiviral immune responses associated with chronic HCV infection.
Hemodialysis Membranes
Authors: Walter H. Ho[Combining Diaeresis]rl
Journal: Journal of the American Society of Nephrology (2002)

Maintenance hemodialysis patients display evidence of elevated interleukin-1 (IL-1) and tumor necrosis factor alpha release after stimulation either by contaminated dialysate, bioincompatible membrane material, or both. This release is followed by the stimulated secretion of a large number of other interleukins, particularly IL-6, the cytokine principally responsible for acute-phase protein synthesis. It has been shown that high levels of the circulating proinflammatory cytokines IL-1, tumor necrosis factor alpha, IL-6, and IL-13 are associated with mortality in hemodialysis patients. Essential functions of polymorphonuclear leukocytes--that is, phagocytosis, oxygen species production, upregulation of specific cell surface receptor proteins, or apoptosis--are disturbed in patients with end-stage renal disease. These are further altered as a result of complement activation by the hemodialysis procedure, particularly if bioincompatible dialyzers are used. Polymorphonuclear leukocyte degranulation occurring during extracorporeal circulation does not depend on complement activation but rather on intracellular calcium and the presence or absence of the degranulation inhibitory proteins angiogenin and complement factor D. Clinical signs and symptoms of end-stage renal disease patients are at least in part related to the accumulation of middle molecules such as beta(2)-microglobulin, parathyroid hormone, advanced glycation end products, advanced lipoxidation end products, advanced oxidation protein products (formed as a result of oxidative stress, carbonyl stress, or both), granulocyte inhibitory proteins, or leptin. Currently available membrane materials do not provide long-lasting, effective reduction of middle molecules in patients who require maintenance hemodialysis.
Differential diagnosis between rheumatoid arthritis and psoriatic arthritis: the value of ultrasound findings at metacarpophalangeal joints level
Authors: Marwin Gutierrez, Emilio Filippucci, Fausto Salaffi, Luca Di Geso, Walter Grassi
Journal: Annals of the Rheumatic Diseases (2011)

Objective To investigate the potential of ultrasound (US) in the differential diagnosis between rheumatoid arthritis (RA) and psoriatic arthritis (PsA) at metacarpophalangeal (MCP) joints level. Methods 18 RA patients and 20 PsA patients with clinical involvement of MCP joints were included. All US examinations were performed by two rheumatologists investigating: presence of joint cavity widening (JCW), synovial fluid and/or synovial hypertrophy, peritenon extensor tendon inflammation (PTI) and intra-articular or peri-tendinous power Doppler (PD) signal. Results A total of 83 MCP joints in 18 RA patients were assessed. In all of these the authors found different degrees of JCW. 15 of 83 (18%) MCP joints showed synovial fluid, whereas 68 of 83 (82%) MCP joints showed synovial hypertrophy. In 72 of 83 (86.7%) MCP joints intra-articular PD was detected. No PTI pattern was found in these patients. In PsA patients, a total of 82 MCP joints in 20 patients were assessed. 54 of 82 (65.8%) MCP joints showed PTI pattern (p = 0.001). In 50 of these 54 (92.5%) MCP joints extra-articular PD signal was detected (p = 0.001). 28 of 82 (34.1%) MCP joints showed different degrees of JCW. 6 of 28 (21.4%) MCP joints presented synovial fluid, whereas 22 of 28 (78.5%) MCP joints showed synovial hypertrophy. In 8 of 82 (9.7%) MCP joints the JCW and PTI patterns were found contemporaneously. Conclusions Preliminary results demonstrate that PTI pattern is a higher characteristic of PsA, which suggests a potential role of US in the differential diagnosis between RA and PsA at MCP joints level.
The mediator of cellular immunity. XII. Inhibition of activated T cells by Newcastle disease virus.
Authors: D D McGregor, P S Logie, L E Carmichael
Journal: The Journal of Experimental Medicine (1976)

Newcastle disease virus (NDV) can interact in at least two ways with rat T cells. By adsorbing to circulating lymphocytes, the virus can transiently deflect the cells from lymph nodes and inflammatory exudates induced in the peritoneal cavity. T cells are affected regardless of age, state of activation, or position in the mitotic cycle. The effect is reversible and is mediated not only by infectious (I)-NDV, but also by UV-NDV which cannot achieve a complete replication cycle in eggs. But I-NDV has another lasting effect on activated T cells. It is revealed in the failure of virus-treated thoracic duct lymphocytes to transfer cellular resistance to Listeria monocytogenes, delayed-type hypersensitivity to soluble antigens of the parasite, and the permanent exclusion of labeled S-phase lymphocytes from inflammatory foci. Activated T cells are inhibited by virus multiplicites which have little if any effect upon the proliferative potential of antigen-sensitive T cells or localization of labeled small lymphocytes in lymph nodes. The underlying mechanism has not been determined; however, there are reasons for thinking that NDV has a lethal effect upon activated T cells, because the latter are permissive for virus replication.
An NQO1 Substrate with Potent Antitumor Activity That Selectively Kills by PARP1-Induced Programmed Necrosis
Authors: Xiumei Huang, Ying Dong, Erik A. Bey, Jessica A. Kilgore, Joseph S. Bair, Long-Shan Li, Malina Patel, Elizabeth I. Parkinson, Yiguang Wang, Noelle S. Williams, Jinming Gao, Paul J. Hergenrother, David A. Boothman
Journal: Cancer Research (2012)

Abstract Agents, such as β-lapachone, that target the redox enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), to induce programmed necrosis in solid tumors have shown great promise, but more potent tumor-selective compounds are needed. Here, we report that deoxynyboquinone kills a wide spectrum of cancer cells in an NQO1-dependent manner with greater potency than β-lapachone. Deoxynyboquinone lethality relies on NQO1-dependent futile redox cycling that consumes oxygen and generates extensive reactive oxygen species (ROS). Elevated ROS levels cause extensive DNA lesions, PARP1 hyperactivation, and severe NAD+/ATP depletion that stimulate Ca2+–dependent programmed necrosis, unique to this new class of NQO1 “bioactivated” drugs. Short-term exposure of NQO1+ cells to deoxynyboquinone was sufficient to trigger cell death, although genetically matched NQO1− cells were unaffected. Moreover, siRNA-mediated NQO1 or PARP1 knockdown spared NQO1+ cells from short-term lethality. Pretreatment of cells with BAPTA-AM (a cytosolic Ca2+ chelator) or catalase (enzymatic H2O2 scavenger) was sufficient to rescue deoxynyboquinone-induced lethality, as noted with β-lapachone. Investigations in vivo showed equivalent antitumor efficacy of deoxynyboquinone to β-lapachone, but at a 6-fold greater potency. PARP1 hyperactivation and dramatic ATP loss were noted in the tumor, but not in the associated normal lung tissue. Our findings offer preclinical proof-of-concept for deoxynyboquinone as a potent chemotherapeutic agent for treatment of a wide spectrum of therapeutically challenging solid tumors, such as pancreatic and lung cancers. Cancer Res; 72(12); 3038–47. ©2012 AACR.
Polymorphism in the LMP2 gene influences susceptibility to extraspinal disease in HLA-B27 positive individuals with ankylosing spondylitis.
Authors: W P Maksymowych, M Suarez-Almazor, C T Chou, A S Russell
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To investigate the potential influence of the HLA-linked LMP2 gene on disease susceptibility in HLA-B27 individuals with ankylosing spondylitis (AS). METHODS--A polymorphic CfoI restriction enzyme site in the coding region of the LMP2 gene was evaluated in genomic DNA samples from 193 white and 49 Chinese B27 individuals with well documented AS, 97 of whom had had acute anterior uveitis (AAU) and 97 peripheral arthritis; 42 samples from normal, white, B27 positive blood donors in whom AS was excluded were also evaluated. RESULTS--Analysis of B27 white AS individuals with AAU, peripheral arthritis, or both, revealed significant differences in genotypic distribution of this bi-allelic locus compared with B27 AS patients without extraspinal manifestations (p &lt; 0.005) or B27 controls (p &lt; 0.01). Furthermore, homozygosity for one LMP2 gene allele was significantly more prevalent in AS patients with AAU (71.3%) (p &lt; 0.01) or peripheral arthritis (68.3%) (p &lt; 0.02) than in B27 controls (45.2%). A similar genotypic distribution was noted in B27 Chinese AS individuals with extraspinal manifestations compared with those with axial disease alone. CONCLUSIONS--These findings support the involvement of the HLA linked LMP2 gene in the expression of disease in B27 individuals and represent a novel finding in rheumatic disease.
Spread of an epidemic Pseudomonas aeruginosa strain from a patient with cystic fibrosis (CF) to non-CF relatives
Authors: S J McCallum
Journal: Thorax (2002)

Colonisation with <i>Pseudomonas aeruginosa</i> is common in adults with cystic fibrosis (CF) and there is increasing evidence that transmissible strains may cross colonise patients. However, transmission of these strains by social contact to healthy non-CF individuals has not been described. A case is presented where an adult CF patient colonised by an epidemic <i>P aeruginosa</i> strain infected her parents with subsequent morbidity.
Helicobacter pylori infection modifies gastric and plasma ghrelin dynamics in Mongolian gerbils
Authors: H Suzuki
Journal: Gut (2004)

<b>Background and aim:</b> Although ghrelin, a novel growth hormone releasing peptide localised mainly in the gastric fundus, is reported not only to accelerate food passage and gastrointestinal motility but also to affect appetite and weight control, regulation of gastric ghrelin secretion under the conditions of gastric <i>Helicobacter pylori</i> infection is unknown. The present study was designed to investigate plasma and gastric ghrelin levels in Mongolian gerbils with <i>H pylori</i> colonisation of the gastric mucosa. <b>Methods:</b> Gerbils orally inoculated with <i>H pylori</i> were examined after inoculation. To examine preproghrelin mRNA expression in the gastric mucosa, cDNA encoding the gerbil preproghrelin and glyceraldehyde-3-phosphate dehydrogenase homologue was isolated and a quantitative reverse transcription-polymerase chain reaction system was established. <b>Results:</b> In gerbils showing <i>H pylori</i> colonisation (<i>H pylori</i> group), expression of preproghrelin mRNA and total ghrelin levels were significantly decreased 17 and 23 weeks later (p&lt;0.01). Although the number of ghrelin immunoreactive cells decreased as the stomach weight increased, the gastric contents of total and active ghrelin in this group were the same as those in controls. Gastric myeloperoxidase activity showed a positive correlation with plasma ghrelin levels. On the other hand, at 17 weeks, plasma ghrelin levels were significantly increased in the <i>H pylori</i> group (p&lt;0.05), suggesting a compensatory increase in secretion of the peptide at this time point. <b>Conclusion:</b> The present experimental study demonstrated that gastric and plasma ghrelin dynamics are altered in response to <i>H pylori</i> infection.
Topographic Basis of Bimodal Ventilation–Perfusion Distributions during Bronchoconstriction in Sheep
Authors: Marcos F. Vidal Melo, R. Scott Harris, J. Dominick H. Layfield, Jose G. Venegas
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

The distribution of ventilation-perfusion (VA/Q) ratios during bronchoconstriction measured with the multiple inert gases elimination technique is frequently bimodal. However, the topographic basis and the cause of that bimodality remain unknown. In this article, regional VA/Q is quantified by three-dimensional positron emission tomography (PET) imaging of methacholine-induced bronchoconstriction in sheep. Regional VA/Q ratios were calculated from the imaged kinetics of intravenously injected 13NN-saline bolus, assembled into global VA/Q distributions, and used to estimate gas exchange. During bronchoconstriction, large regions with impaired tracer washout were observed adjacent to regions of normal ventilation. PET-derived VA/Q distributions during bronchoconstriction were consistently bimodal, with areas of low VA/Q receiving a large fraction of Q. The standard deviation of the VA/Q distribution was 38% lower if small-scale (subresolution) heterogeneity (< 2.2 cm3) was ignored. Arterial blood gases predicted from PET data correlated well with measured values for Pa(O2) (r2= 0.91, p < 0.01) and Pa(CO2) (r2= 0.90, p < 0.01). We conclude that the bimodality of VA/Q distributions in bronchoconstriction reflects the involvement of large contiguous regions of hypoventilation with substantial subresolution intraregional VA/Q heterogeneity. Assessment of the subresolution VA/Q heterogeneity is therefore essential to accurately quantify global gas exchange impairment during bronchoconstriction.
Classification and management of refractory coeliac disease
Authors: A. Rubio-Tapia, J. A Murray
Journal: Gut (2010)

Refractory coeliac disease (RCD) is defined by persistent or recurrent malabsorptive symptoms and villous atrophy despite strict adherence to a gluten-free diet (GFD) for at least 6–12 months in the absence of other causes of non-responsive treated coeliac disease and overt malignancy. Symptoms are often severe and require additional therapeutic intervention besides a GFD. RCD can be classified as type 1 (normal intraepithelial lymphocyte phenotype), or type 2 (defined by the presence of abnormal (clonal) intraepithelial lymphocyte phenotype). Patients with RCD may never have responded to a GFD or may have relapsed despite adherence and initial response to the GFD. RCD type 1 usually improves after treatment with a combination of aggressive nutritional support, adherence to a GFD, and alternative pharmacological therapies. By contrast, clinical response to alternative therapies in RCD type 2 is less certain and the prognosis is poor. Severe complications such as ulcerative jejunitis and enteropathy-associated T cell lymphoma may occur in a subgroup of patients with RCD. The aims of this article are to (1) review recent advances in the diagnosis and management of patients with RCD, and (2) describe current and novel methods for classification of patients with RCD into categories that are useful to predict outcome and direct treatment.