tbuckley/cabot-search huggingface dataset:
Vitamin D Deficiency Is More Common in Type 2 Than in Type 1 Diabetes
Authors: David J. Di Cesar, Robert Ploutz-Snyder, Ruth S. Weinstock, Arnold M. Moses
Journal: Diabetes Care (2006)

We report data from a pilot study examining vitamin D deficiency in type 1 and type 2 diabetes. Serum 25-OH vitamin D (25-OH-D) levels were measured in type 1 ( n = 50) and type 2 diabetic ( n = 63) individuals at the time of their routine visits for diabetes management. Patients had no prior history of metabolic bone disease, vitamin D deficiency, parathyroid disease, malabsorption, or significant elevations of serum creatinine or liver enzymes. Most subjects (74.3%) were prescribed a daily multivitamin as part of their routine diabetes care, but none were taking additional supplements. Serum was obtained during “light” (April to September) and “dark” (October to March) months. Serum 25-OH-D levels were …
Specific IgG subclass antibody pattern to Aspergillus fumigatus in patients with cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA)
Authors: M Skov, T Pressler, H E Jensen, N Hoiby, C Koch
Journal: Thorax (1999)

<h3>BACKGROUND</h3> IgG and IgG subclass antibodies to <i>Aspergillus fumigatus (A fumigatus)</i> were measured in a large population of patients with cystic fibrosis to elucidate a putative antibody pattern specific for allergic bronchopulmonary aspergillosis (ABPA). <h3>METHODS</h3> An ELISA technique using water soluble somatic hyphal (WSSH)<i>A fumigatus </i>antigens and subclass specific monoclonal antibodies was used for cross sectional quantification of IgG and IgG<sub>1–4</sub> subclass antibody levels in the serum of 238 patients with cystic fibrosis and 107 healthy controls. <h3>RESULTS</h3> In patients with cystic fibrosis persistently colonised with <i>A fumigatus</i> the subclass antibody levels were significantly increased compared with patients with cystic fibrosis never or rarely colonised (p&lt;0.001). The group of patients persistently colonised with<i>A fumigatus</i> with ABPA (+Af+ABPA) had significantly increased levels of IgG antibodies to<i>A fumigatus</i> (Af-IgG) (median 69 ELISA units (EU) versus 31) and of subclasses Af-IgG<sub>1</sub> (91 versus 27), Af-IgG<sub>2</sub>(143 versus 56), and Af-IgG<sub>4</sub> antibodies (72 versus 20), but not of IgG<sub>3</sub> (17 versus 15), compared with the colonised patients without ABPA (+Af–ABPA). Patients with cystic fibrosis with no or only rare isolates of <i>A fumigatus</i>without ABPA (–Af–ABPA) also had significantly increased subclass antibody levels (Af-IgG<sub>1</sub> 9 versus 3, Af-IgG<sub>2</sub> 28 versus 5, Af-IgG<sub>4</sub> 16 versus 4; p&lt;0.001) compared with healthy controls. Low, although detectable, levels of antibodies were demonstrated in healthy controls. ABPA seemed to occur independently of <i>Pseudomonas aeruginosa</i>infection. Using diagnostic cut off levels for ABPA, sensitivity and specificity were calculated. The highest specificity was found for IgG<sub>4</sub> (88%); sensitivity was between 65% and 73%. The positive predictive values (PPV) were moderate, whereas the negative predictive values (NPV) were high (96% in all subclasses except IgG<sub>3</sub> with 94%). PPV increased to 50% if IgG<sub>1</sub>as well as IgG<sub>2</sub> and IgG<sub>4</sub> were included. <h3>CONCLUSIONS</h3> In a large number of unselected patients with cystic fibrosis significantly increased levels of Af-specific antibodies belonging to total IgG and all four subclasses were found in all groups of patients compared with healthy controls. In patients persistently colonised with<i>A fumigatus</i> these levels were significantly higher than in non-colonised patients, and the significantly highest levels (with the exception of IgG<sub>3</sub>) were found in patients with ABPA. Using a sensitive ELISA technique, measurements of IgG and IgG subclass antibodies to <i>A fumigatus</i> might be of importance in the management of ABPA, especially as a screening test to exclude the presence of ABPA; other tests are needed to confirm the diagnosis.
Role of neutrophil adherence receptors (CD 18) in lung permeability following lower torso ischemia.
Authors: R Welbourn, G Goldman, L Kobzik, I S Paterson, C R Valeri, D Shepro, H B Hechtman
Journal: Circulation Research (1992)

Ischemia and reperfusion of the lower torso lead to leukotriene- and neutrophil (PMN)-dependent lung injury characterized by lung PMN sequestration, increased permeability, and noncardiogenic edema. It is thought that PMNs require adhesion to endothelium to alter barrier function. This study tests the role of CD 18, the PMN adherence receptor, in mediating lung permeability after lower torso ischemia and reperfusion. Anesthetized rabbits (n = 9) underwent 3 hours of bilateral hind limb ischemia. Ten minutes after the release of the tourniquets, plasma leukotriene B4 levels increased to 395 +/- 85 pg/ml, higher than 129 +/- 35 pg/ml in controls (n = 9, p less than 0.01). At this time there was a reduction in circulating white blood cells (x 10(3)), 3.56 +/- 0.49/mm3 relative to 6.07 +/- 0.61/mm3 in controls (p less than 0.01). PMNs were sequestered in the hind limbs, indicated by increased myeloperoxidase activity of 1.06 +/- 0.19 units/g compared with 0.56 +/- 0.09 units/g in controls (p less than 0.05). Four hours after tourniquet release, PMNs were sequestered in the lungs, 52 +/- 4 PMNs per 10 high-power fields, a value higher than 31.5 +/- 3 PMNs per 10 high-power fields in controls; bronchoalveolar lavage fluid protein content increased to 554 +/- 90 micrograms/ml relative to 277 +/- 46 micrograms/ml in controls; and there was lung edema, measured by increased wet weight-to-dry weight ratios of 5.19 +/- 0.10, higher than 4.29 +/- 0.21 in controls (all p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
The Labile Side of Iron Supplementation in CKD
Authors: Itzchak Slotki, Zvi Ioav Cabantchik
Journal: Journal of the American Society of Nephrology (2015)

The practice of intravenous iron supplementation has grown as nephrologists have gradually moved away from the liberal use of erythropoiesis-stimulating agents as the main treatment for the anemia of CKD. This approach, together with the introduction of large-dose iron preparations, raises the future specter of inadvertent iatrogenic iron toxicity. Concerns have been raised in original studies and reviews about cardiac complications and severe infections that result from long-term intravenous iron supplementation. Regarding the iron preparations specifically, even though all the currently available preparations appear to be relatively safe in the short term, little is known regarding their long-term safety. In this review we summarize current knowledge of iron metabolism with an emphasis on the sources and potentially harmful effects of labile iron, highlight the approaches to identifying labile iron in pharmaceutical preparations and body fluids and its potential toxic role as a pathogenic factor in the complications of CKD, and propose methods for its early detection in at-risk patients.
Sulfonylurea Treatment in Young Children With Neonatal Diabetes: Dealing with hyperglycemia, hypoglycemia, and sick days
Authors: Ethel Codner, Sarah E. Flanagan, Francisca Ugarte, Hernán García, Teresa Vidal, Sian Ellard, Andrew T. Hattersley
Journal: Diabetes Care (2007)

Recently, heterozygous activating mutations in the genes forming the ATP-sensitive K+ channel (KATP channel), KCNJ11 and ABCC8 , have been shown to cause neonatal diabetes (1–4). Sulfonylurea treatment restores insulin secretion in these patients (3,5,6), but information on the practical management of children with mutated KATP channels taking this medication is limited.

We report clinical aspects of the successful transfer to oral treatment in three cases of young children with KCNJ11 and ABCC8 mutations (Table 1). All parents gave written consent.

In case 1, a girl was transferred from insulin to glibenclamide at 17 months (7) and had been on this treatment for 2 years. During this period, blood glucose testing decreased …
“Loop Clip”, a new closure device for large mucosal defects after EMR and ESD
Authors: N. Sakamoto, K. Beppu, K. Matsumoto, T. Shibuya, T. Osada, H. Mori, Y. Shimada, A. Konno, A. Kurosawa, A. Nagahara, M. Otaka, T. Ohkusa, T. Ogihara, S. Watanabe
Journal: Endoscopy (2008)

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are indicated for the treatment of large early-stage superficial colorectal cancers. Bleeding and perforation are common complications of EMR and ESD, but closure of the mucosal defect reduces the risk of complications. Hemoclips have been used for endoscopic closure of EMR defects, but they can only be used when the diameter of the defect is less than the width of the open clip. Because it is quite difficult to do, it is not common to close large mucosal defects despite the increased risk of bleeding and perforation. A few techniques involving closure devices have been reported [1] [2], but these complicated methods have not been widely employed because of the need for a 2-channel colonoscope. Therefore, we designed a new closure device for large mucosal defects, named a "loop clip".
MicroRNA-148b is frequently down-regulated in gastric cancer and acts as a tumor suppressor by inhibiting cell proliferation
Authors: Yong-Xi Song, Zhen-Yu Yue, Zhen-Ning Wang, Ying-Ying Xu, Yang Luo, Hui-Mian Xu, Xue Zhang, Li Jiang, Cheng-Zhong Xing, Yong Zhang
Journal: Molecular Cancer (2011)

Abstract Background MicroRNAs (miRNAs) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Our previous studies have revealed that miR-148a and miR-152 are significantly down-regulated in gastrointestinal cancers. Interestingly, miR-148b has the same "seed sequences" as miR-148a and miR-152. Although aberrant expression of miR-148b has been observed in several types of cancer, its pathophysiologic role and relevance to tumorigenesis are still largely unknown. The purpose of this study was to elucidate the molecular mechanisms by which miR-148b acts as a tumor suppressor in gastric cancer. Results We showed significant down-regulation of miR-148b in 106 gastric cancer tissues and four gastric cancer cell lines, compared with their non-tumor counterparts by real-time RT-PCR. In situ hybridization of ten cases confirmed an overt decrease in the level of miR-148b in gastric cancer tissues. Moreover, the expression of miR-148b was demonstrated to be associated with tumor size (P = 0.027) by a Mann-Whitney U test. We also found that miR-148b could inhibit cell proliferation in vitro by MTT assay, growth curves and an anchorage-independent growth assay in MGC-803, SGC-7901, BGC-823 and AGS cells. An experiment in nude mice revealed that miR-148b could suppress tumorigenicity in vivo . Using a luciferase activity assay and western blot, CCKBR was identified as a target of miR-148b in cells. Moreover, an obvious inverse correlation was observed between the expression of CCKBR protein and miR-148b in 49 pairs of tissues (P = 0.002, Spearman's correlation). Conclusions These findings provide important evidence that miR-148b targets CCKBR and is significant in suppressing gastric cancer cell growth. Maybe miR-148b would become a potential biomarker and therapeutic target against gastric cancer.
Science, medicine, and the future: Stem cell transplantation
Authors: A L Lennard
Journal: BMJ (2000)

Stem cell transplantation is a generic term covering several different techniques (see fig 1). Allogeneic transplants are haemopoietic stem cells from the bone marrow, peripheral blood, or umbilical cord blood of a healthy donor matched for HLA type, who may be a family member or an unrelated volunteer. Autologous transplants are stem cells from the patient's own bone marrow or peripheral blood.

Allogeneic transplantation was first used to treat congenital immune deficiencies, bone marrow failure, and haematological malignancies and is now used routinely for some non-malignant conditions such as thalassaemia. Autologous transplantation was introduced to rescue the bone marrow of patients due to undergo high dose chemotherapy, and it is now increasingly written into protocols for the primary treatment of solid tumours such as breast cancer and neuroblastoma. Autologous transplantation is also used experimentally to treat difficult autoimmune conditions such as systemic sclerosis and as a vehicle for gene therapy. Knowledge of stem cell transplantation techniques and their clinical application is therefore becoming essential for increasing numbers of medical specialists.

Our review is based on current haematological textbooks, review articles in major haematological journals, and information from recent meetings of learned societies such as the American Society of Haematology and the European Bone Marrow Transplant Society. This review reflects our personal perspectives and is not meant to cover every likely use or possible advance within this rapidly expanding field.

The first successful bone marrow transplant in humans was performed between identical twins. With a greater understanding of the HLA system, it became possible to perform bone marrow transplants between siblings who were fully HLA identical. Transplantation is widely used for treating congenital bone marrow disorders and malignant haematological diseases. Today, over 350 centres in Europe are performing more than 18 000 bone marrow transplants a year. Centres may report their …
Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels.
Authors: B S Rubin, M K Murray, D A Damassa, J C King, A M Soto
Journal: Environmental Health Perspectives (2001)

The nonsteroidal estrogenic compound bisphenol A (BPA) is a monomer used in the manufacture of polycarbonate plastics and resins. BPA may be ingested by humans as it reportedly leaches from the lining of tin cans into foods, from dental sealants into saliva, and from polycarbonate bottles into their contents. Because BPA is weakly estrogenic--approximately 10,000-fold less potent than 17beta-estradiol--current environmental exposure levels have been considered orders of magnitude below the dose required for adverse effects on health. Herein we demonstrate measurable effects on the offspring of Sprague-Dawley female rats that were exposed, via their drinking water, to approximately 0.1 mg BPA/kg body weight (bw)/day (low dose) or 1.2 mg BPA/kg bw/day (high dose) from day 6 of pregnancy through the period of lactation. Offspring exposed to BPA exhibited an increase in body weight that was apparent soon after birth and continued into adulthood. In addition, female offspring exposed perinatally to the high dose of BPA exhibited altered patterns of estrous cyclicity and decreased levels of plasma luteinizing hormone (LH) in adulthood. Administration of neither the doses of BPA that caused effects during perinatal exposure nor a 10-fold higher dose was able to evoke a uterotropic response in ovariectomized postpubertal females. These data indicate an increased sensitivity to BPA during the perinatal period and suggest the need for careful evaluation of the current levels of exposure to this compound.
Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin
Authors: Martine Gilard, Bertrand Arnaud, Jean-Christophe Cornily, Grégoire Le Gal, Karine Lacut, Geneviève Le Calvez, Jacques Mansourati, Dominique Mottier, Jean-François Abgrall, Jacques Boschat
Journal: Journal of the American College of Cardiology (2008)
Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts
Authors: J. Graeme Hodgson, Ru-Fang Yeh, Amrita Ray, Nicholas J. Wang, Ivan Smirnov, Mamie Yu, Sujatmi Hariono, Joachim Silber, Heidi S. Feiler, Joe W. Gray, Paul T. Spellman, Scott R. Vandenberg, Mitchel S. Berger, C. David James
Journal: Neuro-Oncology (2009)

Development of model systems that recapitulate the molecular heterogeneity observed among glioblastoma multiforme (GBM) tumors will expedite the testing of targeted molecular therapeutic strategies for GBM treatment. In this study, we profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX), and compared GBMX molecular signatures to those observed in GBM clinical specimens derived from the Cancer Genome Atlas (TCGA). The predominant copy number signature in both tumor groups was defined by chromosome-7 gain/chromosome-10 loss, a poor-prognosis genetic signature. We also observed, at frequencies similar to that detected in TCGA GBM tumors, genomic amplification and overexpression of known GBM oncogenes, such as EGFR, MDM2, CDK6, and MYCN, and novel genes, including NUP107, SLC35E3, MMP1, MMP13, and DDX1. The transcriptional signature of GBMX tumors, which was stable over multiple subcutaneous passages, was defined by overexpression of genes involved in M phase, DNA replication, and chromosome organization (MRC) and was highly similar to the poor-prognosis mitosis and cell-cycle module (MCM) in GBM. Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1, which form a transcriptional network important for G2/M progression and/or checkpoint activation. Our study supports propagation of GBM tumors as subcutaneous xenografts as a useful approach for sustaining key molecular characteristics of patient tumors, and highlights therapeutic opportunities conferred by this GBMX tumor panel for testing targeted therapeutic strategies for GBM treatment.
PDZ Domains and the Organization of Supramolecular Complexes
Authors: Morgan Sheng, Carlo Sala
Journal: Annual Review of Neuroscience (2001)

▪ Abstract PDZ domains are modular protein interaction domains that bind in a sequence-specific fashion to short C-terminal peptides or internal peptides that fold in a β-finger. The diversity of PDZ binding specificities can be explained by variable amino acids lining the peptide-binding groove of the PDZ domain. Abundantly represented in Caenorhabditis elegans, Drosophila melanogaster, and mammalian genomes, PDZ domains are frequently found in multiple copies or are associated with other protein-binding motifs in multidomain scaffold proteins. PDZ-containing proteins are typically involved in the assembly of supramolecular complexes that perform localized signaling functions at particular subcellular locations. Organization around a PDZ-based scaffold allows the stable localization of interacting proteins and enhances the rate and fidelity of signal transduction within the complex. Some PDZ-containing proteins are more dynamically regulated in distribution and may also be involved in the trafficking of interacting proteins within the cell.
Ulcerative colitis specific cytotoxic IgG-autoantibodies against colonic epithelial cancer cells.
Authors: I O Auer, L Grosch, C Hardorfer, A Roder
Journal: Gut (1988)

Serum antibodies cytotoxic to the colon cancer cell line RPMI 4788 were studied in 42 patients with ulcerative colitis, 61 patients with Crohn9s disease, 27 patients with other inflammatory diseases (disease-controls) and 22 healthy controls. Cytotoxicity of antibodies towards RPMI 4788 was studied by means of a chromium release assay using peripheral blood mononuclear leucocytes of healthy subjects as effector cells. Using a four hour antibody dependent cell mediated cytotoxicity assay sera from 29% of ulcerative colitis patients contained antibodies cytotoxic for the target, while only 3% of the Crohn9s patients and 6% of the disease controls and non of the healthy controls were positive. When an 18 hour assay was applied, however, not only 40% of ulcerative colitis patients, but also 14% of Crohn9s patients and 21% of disease controls were found positive. The reactive antibody in the four hour assay was mainly of the IgG class, which points at a classical antibody dependent cell mediated cytotoxicity mechanism. In the 18 hour cytotoxic assay IgG and particularly IgM antibodies were found to be reactive. This suggests that in the latter case other cellular cytotoxic mechanism might be involved. There was a significant inverse correlation between the appearance of the ulcerative colitis restricted IgG-anticolon epithelial cell antibodies (four hour assay) and the disease activity (p less than 0.01). Absorption studies showed that the reactive antigen is not specific for ulcerative colitis colonic tissue, but is similarly found in Crohn9s bowel tissue, and to a lower extent in normal bowel, liver and kidney. The reactive antigen, however, could not be detected in brain and lymphoblastoid cells.
Vitamin D Levels and Risk of Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Ken M. Kunisaki, Dennis E. Niewoehner, John E. Connett
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Low blood levels of 25-hydroxyvitamin D (25[OH]D) have been associated with a higher risk of respiratory infections in general populations and higher risk of exacerbations of lung disease in people with asthma. We hypothesized that low blood levels of 25(OH)D in patients with chronic obstructive pulmonary disease (COPD) would be associated with an increased risk of acute exacerbations of COPD (AECOPD).To determine if baseline 25(OH)D levels relate to subsequent AECOPD in a cohort of patients at high risk for AECOPD.Plasma 25(OH)D was measured at baseline in 973 participants on entry to a 1-year study designed to determine if daily azithromycin decreased the incidence of AECOPD. Relationships between baseline 25(OH)D and AECOPD over 1 year were analyzed with time to first AECOPD as the primary outcome and exacerbation rate as the secondary outcome.In this largely white (85%) sample of North American patients with severe COPD (mean FEV(1) 1.12L; 40% of predicted), mean 25(OH)D was 25.7 ± 12.8 ng/ml. A total of 33.1% of participants were vitamin D insufficient (≥20 ng/ml but <30 ng/ml); 32% were vitamin D deficient (<20 ng/ml); and 8.4% had severe vitamin D deficiency (<10 ng/ml). Baseline 25(OH)D levels had no relationship to time to first AECOPD or AECOPD rates.In patients with severe COPD, baseline 25(OH)D levels are not predictive of subsequent AECOPD. Clinical trial registered with www.clinicaltrials.gov (NCT00119860).