tbuckley/cabot-search huggingface dataset:
Self-Monitoring of Blood Glucose in Type I Diabetic Patients: Comparison With Continuous Microdialysis Measurements of Glucose in Subcutaneous Adipose Tissue During Ordinary Life Conditions
Authors: Jan Bolinder, Eva Hagström-Toft, Urban Ungerstedt, Peter Arner
Journal: Diabetes Care (1997)

OBJECTIVE To evaluate whether frequent self-monitoring of blood glucose (SMBG) sufficiently reflects the true diurnal glucose control during ordinary daily life in type I diabetic patients. RESEARCH DESIGN AND METHODS By using a microdialysis technique, continuous monitoring of adipose tissue glucose was performed in 24 type I diabetic patients during ambulatory conditions. A microdialysis probe was implanted subcutaneously and perfused by a portable microinfusion pump. Dialysate fractions were collected in 1- to 2-h samples during 3 consecutive days. The diurnal microdialysis glucose profiles were compared with those obtained by SMBG recordings performed seven times a day. RESULTS In seven patients, the SMBG profiles showed marked aberrations as compared to the continuous microdialysis glucose recordings; during the 3-day study period, 5–6 inconsistencies were registered. In only 4 patients (17%) did SMBG provide a valid reflection (0–2 inconsistencies) of the diurnal glucose profile, whereas in 13 patients the SMBG recordings paralleled the diurnal adipose tissue glucose profiles in an intermediate way (3–4 major inconsistencies). The inaccuracy of the SMBG data was due more often to the fact that wide glucose swings remained unrecognized, rather than to erroneous testing techniques (P &amp;lt; 0.05), and it was more evident during the night (P &amp;lt; 0.05). CONCLUSIONS In many type I diabetic patients, the true diurnal variability in glycemia is too great to be accurately reflected even by frequent self-monitoring of blood glucose.
Genetic regulation of gene expression in the lung identifies<i>CST3</i>and<i>CD22</i>as potential causal genes for airflow obstruction
Authors: Maxime Lamontagne, Wim Timens, Ke Hao, Yohan Bossé, Michel Laviolette, Katrina Steiling, Joshua D Campbell, Christian Couture, Massimo Conti, Karen Sherwood, James C Hogg, Corry-Anke Brandsma, Maarten van den Berge, Andrew Sandford, Stephen Lam, Marc E Lenburg, Avrum Spira, Peter D Paré, David Nickle, Don D Sin, Dirkje S Postma
Journal: Thorax (2014)

<h3>Background</h3> COPD is a complex chronic disease with poorly understood pathogenesis. Integrative genomic approaches have the potential to elucidate the biological networks underlying COPD and lung function. We recently combined genome-wide genotyping and gene expression in 1111 human lung specimens to map expression quantitative trait loci (eQTL). <h3>Objective</h3> To determine causal associations between COPD and lung function-associated single nucleotide polymorphisms (SNPs) and lung tissue gene expression changes in our lung eQTL dataset. <h3>Methods</h3> We evaluated causality between SNPs and gene expression for three COPD phenotypes: FEV<sub>1</sub>% predicted, FEV<sub>1</sub>/FVC and COPD as a categorical variable. Different models were assessed in the three cohorts independently and in a meta-analysis. SNPs associated with a COPD phenotype and gene expression were subjected to causal pathway modelling and manual curation. <i>In silico</i> analyses evaluated functional enrichment of biological pathways among newly identified causal genes. Biologically relevant causal genes were validated in two separate gene expression datasets of lung tissues and bronchial airway brushings. <h3>Results</h3> High reliability causal relations were found in SNP–mRNA–phenotype triplets for FEV<sub>1</sub>% predicted (n=169) and FEV<sub>1</sub>/FVC (n=80). Several genes of potential biological relevance for COPD were revealed. eQTL-SNPs upregulating cystatin C (<i>CST3</i>) and <i>CD22</i> were associated with worse lung function. Signalling pathways enriched with causal genes included xenobiotic metabolism, apoptosis, protease–antiprotease and oxidant–antioxidant balance. <h3>Conclusions</h3> By using integrative genomics and analysing the relationships of COPD phenotypes with SNPs and gene expression in lung tissue, we identified <i>CST3</i> and <i>CD22</i> as potential causal genes for airflow obstruction. This study also augmented the understanding of previously described COPD pathways.
Upper Airway Size Analysis by Magnetic Resonance Imaging of Children with Obstructive Sleep Apnea Syndrome
Authors: Raanan Arens, Joseph M. McDonough, Aaron M. Corbin, Nathania K. Rubin, Mary Ellen Carroll, Allan I. Pack, Jianguo Liu, Jayaram K. Udupa
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Detailed analysis of the upper airway has not been performed in children with obstructive sleep apnea. We used magnetic resonance imaging and automatic segmentation to delineate the upper airway in 20 children with obstructive sleep apnea and in 20 control subjects (age, 3.7 +/- 1.4 versus 3.9 +/- 1.7 years, respectively). We measured mean and minimal cross-sectional area, length, and volume of: (1) the total airway; (2) regions along the adenoid, tonsils, and where adenoid and tonsils overlap; and (3) 10 segments at 10% increments along the airway. The mean cross-sectional area of the total airway of the obstructive sleep apnea group was significantly smaller in comparison with the control group, 28.1 +/- 12.6 versus 47.1 +/- 18.2 mm2, respectively (p < 0.0005). Minimal cross-sectional area and airway volume were smaller in this group, 4.6 +/- 3.3 versus 15.7 +/- 12.7 mm2 (p < 0.0005), and 1,129 +/- 515 versus 1,794 +/- 846 mm3 (p < 0.005), respectively. Regional analysis suggested that the upper airway in children with obstructive sleep apnea is most restricted where adenoid and tonsils overlap. Segmental analysis demonstrated that the upper airway is restricted throughout the initial two-thirds of its length and that the narrowing is not in a discrete region adjacent to either the adenoid or tonsils, but rather in a continuous fashion along both.
Tuberculosis and the National Health Service Act
Authors: G. L. Cox
Journal: BMJ (1947)

and in the case of the younger men the financial penalties imposed on them if they resign before the end of the three years' probationary service are too great for their slender resources.Those who intend joining the service must know that there is grave discontent among, medical officers in Malaya and that this discontent is amply justified.They must also realize that they can place no trust in the truth of statements concerning conditions of service in the Colonies made to them at their interview in London.These are not the complaints of an inexperienced person who takes badly to service conditions, for I have already had six years with the Navy and am well used to the discipline of that Service.Nor are they those of one who dislikes hard work in a hospital.They are, the bitter -complaints of a man who resigned after six months in the Malayan Medical Service and who has seen his plans for the future destroyed by the deliberate misrepresentations of a supposedly responsible Government Department.-Iam, etc., Singapore.
PWE-150 “The Early Growth Response Genes Induce Apoptosis in Colon Cancer Cells”
Authors: A Koulouris
Journal: Gut (2013)

<h3>Introduction</h3> The Egr familly (Early Growth Respone Genes) of zinc finger transcription factors, which consists of four members; Egr-1, –2, –3 and –4, have been proved to have dynamic functions in the regulation of cell growth and the immune responses.Moreover, in a number of malignancies-which is a cell growth and immune related process- it seems that Egr1 and 2 induce apoptosis leading to the inhibition of the tumour growth. The present study was designed to answer the question whether colon cancer cells undergo apoptosis when the EGR genes are exogenously introduced and if the presence of a mutant p53 can affect this apoptotic pathway. <h3>Methods</h3> Two cell lines deriving from human colon cancer; one p53 negative (DLD1) and another p53 positive (HCT116) were transfected with Egr-1, –2 and –3 and a fluorescent protein which was the marker of the transfection. The transfected cells were incubated for 48 hours. Flow cytometry was used to create a pure population of transfected cells and 24hours later these cells were examined in the fluoroscopic microscope and compared with the controls. <h3>Results</h3> We found that all three Egr members can suppress tumour cell growth suggesting that the function of Egr in the control of cell growth is not associated with the function of p53. In addition to the growth arrest, the transfected cells changed morphology to round shape indicating of senescence. <h3>Conclusion</h3> This may suggest that Egr molecules are important to control the unwanted growth in response to malignant transformation. Our results not only demonstrated an important function of Egr molecules and also indicate the therapeutic potential for the treatment of tumour. <h3>Disclosure of Interest</h3> None Declared.
Proanthocyanidins and other flavonoids in relation to pancreatic cancer: a case–control study in Italy
Authors: M. Rossi, A. Lugo, P. Lagiou, A. Zucchetto, J. Polesel, D. Serraino, E. Negri, D. Trichopoulos, C. La Vecchia
Journal: Annals of Oncology (2011)
Cancer biology may be more important than diagnostic delay
Authors: R Paul Symonds
Journal: BMJ (2002)

EDITOR —Delay in the diagnosis of cancer is universally considered to be unacceptable. The results of the study of treatment delay and survival in women with endometrial cancer in Scotland are therefore counterintuitive.1 Crawford et al found that delay and survival were inversely related. Women with the shortest delay had more advanced disease and had the worst survival. Although these results were unexpected, they are consistent with previous studies in cervix and breast cancer.

An earlier study in the …
THE ACUTE HAEMOLYTIC ANAEMIA OF LEDERER
Authors: H. Joules, L. M. Masterman
Journal: BMJ (1935)

On the other hand, there are decided differences between the strains obtained from the parenits and that from one of their children.The latter strain, obtained from a gastric lavage, is dysgonic-but not so dysgonic as those of the parents-and of full bovine virulence.A goat inoculated intramuscularly with 10 mg. of the culture died in forty-tw'o days of general miliary tuberculosis, the lungs being closely beset with tubercles.Two rabbits inoculated intravenously, doses 0.01 mg., died of severe general miliary tuberculosis in twenty-two and thirty days.Two guinea-pigs inoculated intraperitoneally died of acute general tuberculosis in eighteen and nineteen days, and two inoculated subcutaneously of general tuberculosis in thirtyeight and forty-three days.
The Kidney and Homocysteine Metabolism
Authors: ALLON N. FRIEDMAN, ANDREW G. BOSTOM, JACOB SELHUB, ANDREW S. LEVEY, IRWIN H. ROSENBERG
Journal: Journal of the American Society of Nephrology (2001)

Homocysteine (Hcy) is an intermediate of methionine metabolism that, at elevated levels, is an independent risk factor for vascular disease and atherothrombosis. Patients with renal disease, who exhibit unusually high rates of cardiovascular morbidity and death, tend to be hyperhomocysteinemic, particularly as renal function declines. This observation and the inverse relationship between Hcy levels and GFR implicate the kidney as an important participant in Hcy handling. The normal kidney plays a major role in plasma amino acid clearance and metabolism. The existence in the kidney of specific Hcy uptake mechanisms and Hcy-metabolizing enzymes suggests that this role extends to Hcy. Dietary protein intake may affect renal Hcy handling and should be considered when measuring Hcy plasma flux and renal clearance. The underlying cause of hyperhomocysteinemia in renal disease is not entirely understood but seems to involve reduced clearance of plasma Hcy. This reduction may be attributable to defective renal clearance and/or extrarenal clearance and metabolism, the latter possibly resulting from retained uremic inhibitory substances. Although the currently available evidence is not conclusive, it seems more likely that a reduction in renal Hcy clearance and metabolism is the cause of the hyperhomocysteinemic state. Efforts to resolve this important issue will advance the search for effective Hcy-lowering therapies in patients with renal disease.
A Natural Immunological Adjuvant Enhances T Cell Clonal Expansion through a CD28-dependent, Interleukin (IL)-2–independent Mechanism
Authors: Alexander Khoruts, Anna Mondino, Kathryn A. Pape, Steven L. Reiner, Marc K. Jenkins
Journal: The Journal of Experimental Medicine (1998)

The adoptive transfer of naive CD4+ T cell receptor (TCR) transgenic T cells was used to investigate the mechanisms by which the adjuvant lipopolysaccharide (LPS) enhance T cell clonal expansion in vivo. Subcutaneous administration of soluble antigen (Ag) resulted in rapid and transient accumulation of the Ag-specific T cells in the draining lymph nodes (LNs), which was preceded by the production of interleukin (IL)-2. CD28-deficient, Ag-specific T cells produced only small amounts of IL-2 in response to soluble Ag and did not accumulate in the LN to the same extent as wild-type T cells. Injection of Ag and LPS, a natural immunological adjuvant, enhanced IL-2 production and LN accumulation of wild-type, Ag-specific T cells but had no significant effect on CD28-deficient, Ag-specific T cells. Therefore, CD28 is critical for Ag-driven IL-2 production and T cell proliferation in vivo, and is essential for the LPS-mediated enhancement of these events. However, enhancement of IL-2 production could not explain the LPS-dependent increase of T cell accumulation because IL-2–deficient, Ag-specific T cells accumulated to a greater extent in the LN than wild-type T cells in response to Ag plus LPS. These results indicate that adjuvants improve T cell proliferation in vivo via a CD28-dependent signal that can operate in the absence of IL-2.
Immunogenetic analysis of a panel of monoclonal IgG and IgM anti-PDC-E2/X antibodies derived from patients with primary biliary cirrhosis
Authors: Richard K. Thomson, Zadie Davis, Jeremy M. Palmer, Michael J.P. Arthur, Stephen J. Yeaman, Caroline J. Chapman, Myfanwy B. Spellerberg, Freda K. Stevenson
Journal: Journal of Hepatology (1998)
Urinary type II collagen C-terminal peptide is associated with synovitis and predicts structural bone loss in very early inflammatory arthritis
Authors: J. E. Freeston, P. Garnero, R. J. Wakefield, E. M. A. Hensor, P. G. Conaghan, P. Emery
Journal: Annals of the Rheumatic Diseases (2010)

In rheumatoid arthritis, high levels of the cartilage turnover biomarker C-terminal cross-linking telopeptide of type II collagen (CTX-II) predict an increased risk of radiological progression. In very early inflammatory arthritis erosions are uncommon, therefore CTX-II requires validation against early markers of inflammatory arthritis such as power Doppler ultrasound (PDUS) synovitis and bone mineral density (BMD) loss.In 50 subjects with 12 weeks or less of inflammatory hand symptoms, urinary CTX-II and PDUS were performed at baseline and hand BMD at baseline and 12 months. CTX-II data were log transformed to a normal distribution. Associations between variables were examined using Pearson's r/Spearman's ρ correlations.The mean 12- month change in BMD was -0.0068 g/cm² and the geometric mean for baseline CTX-II/creatinine was 245.89 ng/mmol. Log-transformed baseline CTX-II showed a substantive negative association with change in average BMD over 12 months, controlling for baseline BMD and erythrocyte sedimentation rate (r=-0.359, p=0.044). The median total PDUS score was 3.0 and baseline CTX-II was significantly associated with baseline total PDUS (Spearman's ρ=0.482, p=0.002).Urinary CTX-II correlates with PDUS synovitis and hand BMD reduction very early in the course of inflammatory arthritis, suggesting that CTX-II has potential as a biomarker in very early inflammatory arthritis.
Increased Collagen Synthesis by Scleroderma Skin Fibroblasts In Vitro A POSSIBLE DEFECT IN THE REGULATION OR ACTIVATION OF THE SCLERODERMA FIBROBLAST
Authors: E. Carwile LeRoy
Journal: Journal of Clinical Investigation (1974)

Cultures of dividing skin fibroblasts from normal and sclerodermatous human skin have permitted estimations of soluble collagen concentration, net collagen accumulation, cell-doubling times, and the comparison of morphologic and ultrastructural characteristics. In vitro, the scleroderma fibroblast produces more soluble collagen, synthesizes collagen more rapidly, and fourfold more of its protein synthetic activity is directed to collagen production than in the normal skin fibroblast. Cell-doubling times and morphologic and ultrastructural observations of cells in culture have not provided clues to the nature of the biologic defect in the regulation or activation of collagen synthesis by the scleroderma fibroblast.
Friend of GATA-1 Represses GATA-3–dependent Activity in CD4+ T Cells
Authors: Meixia Zhou, Wenjun Ouyang, Qian Gong, Samuel G. Katz, J. Michael White, Stuart H. Orkin, Kenneth M. Murphy
Journal: The Journal of Experimental Medicine (2001)

The development of naive CD4+ T cells into a T helper (Th) 2 subset capable of producing interleukin (IL)-4, IL-5, and IL-13 involves a signal transducer and activator of transcription (Stat)6-dependent induction of GATA-3 expression, followed by Stat6-independent GATA-3 autoactivation. The friend of GATA (FOG)-1 protein regulates GATA transcription factor activity in several stages of hematopoietic development including erythrocyte and megakaryocyte differentiation, but whether FOG-1 regulates GATA-3 in T cells is uncertain. We show that FOG-1 can repress GATA-3–dependent activation of the IL-5 promoter in T cells. Also, FOG-1 overexpression during primary activation of naive T cells inhibited Th2 development in CD4+ T cells. FOG-1 fully repressed GATA-3–dependent Th2 development and GATA-3 autoactivation, but not Stat6-dependent induction of GATA-3. FOG-1 overexpression repressed development of Th2 cells from naive T cells, but did not reverse the phenotype of fully committed Th2 cells. Thus, FOG-1 may be one factor capable of regulating the Th2 development.
Loss of MicroRNA-192 Promotes Fibrogenesis in Diabetic Nephropathy
Authors: Aleksandra Krupa, Robert Jenkins, Dong Dong Luo, Aled Lewis, Aled Phillips, Donald Fraser
Journal: Journal of the American Society of Nephrology (2010)

The role of microRNAs (miRs), which are endogenous RNA oligonucleotides that regulate gene expression, in diabetic nephropathy is unknown. Here, we performed expression profiling of cultured proximal tubular cells (PTCs) under high-glucose and control conditions. We identified expression of 103 of 328 microRNAs but did not observe glucose-induced changes in expression. Next, we performed miR expression profiling in pooled RNA from formalin-fixed, paraffin-embedded tissue from renal biopsies. We studied three groups of patients with established diabetic nephropathy and detected 103 of 365 miRs. Two miRs differed by more than two-fold between progressors and nonprogressors, and 12 miRs differed between late presenters and other biopsies. We noted the greatest change in miR-192 expression, which was significantly lower in late presenters. Furthermore, in individual biopsies, low expression of miR-192 correlated with tubulointerstitial fibrosis and low estimated GFR. In vitro, treatment of PTCs with TGF-beta1 decreased miR-192 expression. Overexpression of miR-192 suppressed expression of the E-Box repressors ZEB1 and ZEB2, thereby opposing TGF-beta-mediated downregulation of E-cadherin. In summary, loss of miR-192 expression associates with increased fibrosis and decreased estimated GFR in diabetic nephropathy in vivo, perhaps by enhancing TGF-beta-mediated downregulation of E-cadherin in PTCs.
Cardiac Na <sup>+</sup> Channel Dysfunction in Brugada Syndrome Is Aggravated by β <sub>1</sub> -Subunit
Authors: Naomasa Makita, Nobumasa Shirai, Dao W. Wang, Koji Sasaki, Alfred L. George, Morio Kanno, Akira Kitabatake
Journal: Circulation (2000)

Background —Mutations in the gene encoding the human cardiac Na + channel α-subunit (hH1) are responsible for chromosome 3–linked congenital long-QT syndrome (LQT3) and idiopathic ventricular fibrillation (IVF). An auxiliary β 1 -subunit, widely expressed in excitable tissues, shifts the voltage dependence of steady-state inactivation toward more negative potentials and restores normal gating kinetics of brain and skeletal muscle Na + channels expressed in Xenopus oocytes but has little if any functional effect on the cardiac isoform. Here, we characterize the altered effects of a human β 1 -subunit (hβ 1 ) on the heterologously expressed hH1 mutation (T1620M) previously associated with IVF. Methods and Results —When expressed alone in Xenopus oocytes, T1620M exhibited no persistent currents, in contrast to the LQT3 mutant channels, but the midpoint of steady-state inactivation (V 1/2 ) was significantly shifted toward more positive potentials than for wild-type hH1. Coexpression of hβ 1 did not significantly alter current decay or recovery from inactivation of wild-type hH1; however, it further shifted the V 1/2 and accelerated the recovery from inactivation of T1620M. Oocyte macropatch analysis revealed that the activation kinetics of T1620M were normal. Conclusions —It is suggested that coexpression of hβ 1 exposes a more severe functional defect that results in a greater overlap in the relationship between channel inactivation and activation (window current) in T1620M, which is proposed to be a potential pathophysiological mechanism of IVF in vivo. One possible explanation for our finding is an altered α-/β 1 -subunit association in the mutant.
HPV-Positive Oropharyngeal Cancer: Data May Justify New Approach
Authors: J. Peres
Journal: JNCI Journal of the National Cancer Institute (2010)

patients had better 3-year rates of overall survival (82.4%) than those with HPVnegative tumors (57.1%). HPV-positive patients also had better progression-free survival (73.7% vs. 43.4%) at 3 years. The authors, led by Kian Ang, M.D., Ph.D. , a professor of radiation oncology at the M. D. Anderson Cancer Center in Houston, concluded that those results were “consistent with the hypothesis that HPVpositive and HPV-negative oropharyngeal squamous-cell carcinomas are distinct and have different causes, risk-factor profi les, and survival outcomes.” The differences are striking. The main