tbuckley/cabot-search huggingface dataset:
SLC4A7 sodium bicarbonate co-transporter controls mitochondrial apoptosis in ischaemic coronary endothelial cells
Authors: S. Kumar, J.-P. Flacke, S. Kostin, A. Appukuttan, H. P. Reusch, Y. Ladilov
Journal: Cardiovascular Research (2010)

AimsBicarbonate transport has been shown to participate in apoptosis under ischaemic stress. However, the precise transporting mechanisms involved in ischaemic apoptosis are unknown and were thus the aim of the present study.
Matrix Metalloproteinase/Tissue Inhibitors of Matrix Metalloproteinase Phenotype Identifies Poor Prognosis Colorectal Cancers
Authors: Stephanie Curran, Sinclair R. Dundas, Jenny Buxton, Matthew F. Leeman, Robin Ramsay, Graeme I. Murray
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes involved in tumor invasion; several individual members of which have been implicated in tumor prognosis. These enzymes and their physiologic inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), act in a coordinated manner to form an integrated system. Therefore, to understand their role in tumor invasion, it is necessary to evaluate them collectively. Experimental Design: In this study all of the major members of the matrix metalloproteinase (MMP-1, MMP-2, MMP-3,MMP-7, MMP-9, MMP-13, MT1-MMP and MT2-MMP)/tissue inhibitor of matrix metalloproteinase (TIMP-1, TIMP-2, and TIMP-3) system have been investigated by immunohistochemistry in a series (n = 90) of stage III (Dukes’ C) colorectal cancers. An immunohistochemical score based on the intensity of immunoreactivity and proportion of immunoreactive cells was established for each MMP and TIMP. Results: The MMP/TIMP profile defined by hierarchical cluster analysis of the immunohistochemical score identifies a distinct group of colorectal cancers with poor prognosis (log-rank test, 12.22, P = 0.0005). The median survival time of patients in this survival group was 18 months compared with a median survival of 49 months in the “good” survival group. Multivariate analysis showed that this profile was independently the most significant prognostic factor (P = 0.001). Conclusions: This study has identified that the MMP/TIMP profile is an independent indicator of poor prognosis in colorectal cancer.
Purified cytochrome b from human granulocyte plasma membrane is comprised of two polypeptides with relative molecular weights of 91,000 and 22,000.
Authors: C A Parkos, R A Allen, C G Cochrane, A J Jesaitis
Journal: Journal of Clinical Investigation (1987)

A new method has been developed for purification of cytochrome b from stimulated human granulocytes offering the advantage of high yields from practical quantities of whole blood. Polymorphonuclear leukocytes were treated with diisopropylfluorophosphate, degranulated and disrupted by nitrogen cavitation. Membranes enriched in cytochrome b were prepared by differential centrifugation. Complete solubilization of the cytochrome from the membranes was achieved in octylglucoside after a 1-M salt wash. Wheat germ agglutinin-conjugated Sepharose 4B specifically bound the solubilized cytochrome b and afforded a threefold purification. Eluate from the immobilized wheat germ agglutinin was further enriched by chromatography on immobilized heparin. The final 260-fold purification of the b-type cytochrome with a 20-30% yield was achieved by velocity sedimentation in sucrose density gradients. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the purified preparation revealed two polypeptides of Mr 91,000 and Mr 22,000. Treatment of the 125I-labeled, purified preparation with peptide:N-glycosidase F, which removes N-linked sugars, decreased relative molecular weight of the larger species to approximately 50,000, whereas beta-elimination, which removes O-linked sugars, had little or no effect on the mobility of the Mr-91,000 polypeptide. Neither of the deglycosylation conditions had any effect on electrophoretic mobility of the Mr-22,000 polypeptide. Disuccinimidyl suberate cross-linked the two polypeptides to a new Mr of 120,000-135,000 by SDS-PAGE. Antibody raised to the purified preparation immunoprecipitated spectral activity and, on Western blots, bound to the Mr-22,000 polypeptide but not the Mr-91,000 polypeptide. Western blot analysis of granulocytes from patients with X-linked chronic granulomatous disease revealed a complete absence of the Mr-22,000 polypeptide. These results (a) suggest that the two polypeptides are in close association and are part of the cytochrome b, (b) provide explanation for the molecular weight discrepancies previously reported for the protein, and (c) further support the involvement of the cytochrome in superoxide production in human neutrophils.
Volume Stress-Induced Peritoneal Endothelin-1 Release in Continuous Ambulatory Peritoneal Dialysis
Authors: STANISLAO MORGERA, SIMONE KUCHINKE, KLEMENS BUDDE, ANDREAS LUN, BERTHOLD HOCHER, HANS-HELLMUT NEUMAYER
Journal: Journal of the American Society of Nephrology (1999)

Abstract. In long-term peritoneal dialysis, functional deterioration of the peritoneal membrane is often associated with proliferative processes of the involved tissues leading to peritoneal fibrosis. In continuous ambulatory peritoneal dialysis (CAPD), failure to achieve target values for adequacy of dialysis is commonly corrected by increasing dwell volume; in case of ultrafiltration failure, osmolarity of the dialysate gets increased. In a prospective study, the impact of increasing dwell volume from 1500 ml to 2500 ml per dwell (volume trial) or changing the osmolarity of the dialysate from 1.36 to 3.86% glucose (hyperosmolarity trial) on the peritoneal endothelin-1 (ET-1) release was analyzed. ET-1 is known to exert significant proliferative activities on a variety of cell types leading to an accumulation of extracellular matrix. A highly significant difference in the cumulative peritoneal ET-1 synthesis was found between the low- and high-volume exchange, whereas differences in the hyperosmolarity setting were only moderate. Sixty minutes after initiating dialysis, the cumulative ET-1 synthesis was 2367 ± 1023 fmol for the 1500 ml versus 6062 ± 1419 fmol for the 2500 dwell ( P &lt; 0.0001) and 4572 ± 969 fmol versus 6124 ± 1473 fmol for the 1.36 and 3.86% glucose dwell ( P &lt; 0.05), respectively. In conclusion, increasing dwell volume leads to a strong activation of the peritoneal paracrine endothelin system. Because ET-1, apart from being a potent vasoactive peptide, contributes to fibrotic remodeling, this study indicates that volume stress-induced ET-1 release might contribute to structural alteration of the peritoneal membrane in long-term peritoneal dialysis.
Role of biomarkers for early detection of lung cancer and chemoprevention
Authors: F.R. Hirsch, D.T. Merrick, W.A. Franklin
Journal: European Respiratory Journal (2002)

Lung cancer is the leading cause of cancer deaths in developed countries. The poor prognosis associated with this disease is closely related to the fact that most lung cancer patients are not identified until their malignancy has reached an advanced stage. Recent advances have added to the understanding of the morphological and molecular characteristics of preinvasive bronchial lesions and early lung cancers. Such information is being used to provide new tests for the detection of lung cancer at early or preinvasive stages, and for identifying targets for therapeutic intervention that can prevent progression to advanced disease. Laser induced fluorescence endoscope bronchoscopy has improved the sensitivity with which preinvasive dysplastic bronchial lesions and early invasive malignancies can be detected. Morphological features of such lesions have been described and can be monitored by follow-up bronchoscopies in order to validate potential chemoprevention treatments. Distinct morphological characteristics such as angiogenic squamous dysplasia also suggest that processes like angiogenesis are present early in the development of lung cancer. Furthermore, tissue obtained from these early lesions has been used to describe alterations in the expression of a number of factors that distinguish these early lesions from normal bronchial epithelium. This could provide molecular markers and targets for the detection and treatment of early lung cancer. Studies to detect these alterations by polymerase chain reaction and/or immunhistochemical analyses of easily obtained specimens such as sputa are helping identifing molecular markers that could be utilized in effective screening programmes. The current article reviews new findings regarding the molecular biology of preinvasive bronchial lesions and early lung cancers, and describes new developments regarding their application in the early detection and chemoprevention of lung cancer.
Type 1 diabetes in children
Authors: Keya Ali, Anthony Harnden, Julie A Edge
Journal: BMJ (2011)

Type 1 diabetes in childhood is one of the commoner long term conditions of childhood. It is treated by specialist teams in secondary care using increasingly intensive insulin regimens, but the onset is generally diagnosed by primary care physicians, sometimes later than is ideal.

#### Case scenario

A 7 year old boy with acute abdominal pain and vomiting is brought to see his general practitioner by his mother. He was being bullied at school, and because his mother attributed his recent onset of bed wetting to stress she did not mention this symptom to the GP. The GP considers appendicitis a possibility but first decides to rule out a urinary tract infection. A urine dipstick test is positive for glucose and ketones. She refers the child at once to the paediatric team for immediate management of his diabetic ketoacidosis.

#### How common is it?

About 30% of children with newly diagnosed diabetes have had at least one related medical visit before the diagnosis, suggesting that medical practitioners are missing the diagnosis.5 Drinking a lot and …
Elastic Properties of the Central Airways in Obstructive Lung Diseases Measured Using Anatomical Optical Coherence Tomography
Authors: Jonathan P. Williamson, Robert A. McLaughlin, William J. Noffsinger, Alan L. James, Vanessa A. Baker, Andrea Curatolo, Julian J. Armstrong, Adrian Regli, Kelly L. Shepherd, Guy B. Marks, David D. Sampson, David R. Hillman, Peter R. Eastwood
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Our understanding of how airway remodeling affects regional airway elastic properties is limited due to technical difficulties in quantitatively measuring dynamic, in vivo airway dimensions. Such knowledge could help elucidate mechanisms of excessive airway narrowing.Objectives: To use anatomical optical coherence tomography (aOCT) to compare central airway elastic properties in control subjects and those with obstructive lung diseases.Methods: After bronchodilation, airway lumen area (Ai) was measured using aOCT during bronchoscopy in control subjects (n = 10) and those with asthma (n = 16), chronic obstructive pulmonary disease (COPD) (n = 9), and bronchiectasis (n = 8). Ai was measured in each of generations 0 to 5 while airway pressure was increased from −10 to 20 cm H2O. Airway compliance (Caw) and specific compliance (sCaw) were derived from the transpulmonary pressure (Pl) versus Ai curves.Measurements and Main Results: Caw decreased progressively as airway generation increased, but sCaw did not differ appreciably across the generations. In subjects with asthma and bronchiectasis, Caw and sCaw were similar to control subjects and the Pl-Ai curves were left-shifted. No significant differences were observed between control and COPD groups.Conclusions: Proximal airway elastic properties are altered in obstructive lung diseases. Although central airway compliance does not differ from control subjects in asthma, bronchiectasis, or COPD, Ai is lower in asthma and the Pl-Ai relationship is left-shifted in both asthma and bronchiectasis, suggesting that airways are maximally distended at lower inflating pressures. Such changes reflect alteration in the balance between airway wall distensibility and radial traction exerted on airways by surrounding lung parenchyma favoring airway narrowing.Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN12607000624482).
Whole body Kt/V from dialysate urea measurements during hemodialysis.
Authors: J Sternby
Journal: Journal of the American Society of Nephrology (1998)

A new method for the calculation of dialysis dose from continuous measurements of dialysate urea concentrations has been developed. It is based on urea mass in the patient instead of plasma concentrations, and results in a measure of dialysis dose that has been named whole body Kt/V. The measured urea mass removal rate and the slope of the dialysate urea concentration curve are the key parameters needed for the calculations. No assumptions have to be made about urea distribution in the body (single or double pool, etc.). Blood sampling is not needed. This simplifies the logistics and eliminates the problems with rebound and timing in taking samples. The total urea mass present in the body before treatment is also obtained. It can be used directly, or in relation to body weight or water volume, as a measure of the level of urea in the body. This may serve as an alternative to pretreatment plasma concentration. If a pretreatment plasma urea concentration is available, the urea distribution volume can be calculated, which may be of separate clinical interest.
Trends and Disparities in U.S. Emergency Department Visits for Hypoglycemia, 1993–2005
Authors: Adit A. Ginde, Janice A. Espinola, Carlos A. Camargo
Journal: Diabetes Care (2008)

To characterize the epidemiology of hypoglycemia in U.S. emergency departments.We analyzed data from the 1993-2005 National Hospital Ambulatory Medical Care Survey and evaluated trends and disparities over time.There were approximately 5 million emergency department visits for hypoglycemia from 1993-2005, and 25% resulted in hospital admission. The visit rate per 1,000 of the diabetic population was 34 (95% CI 30-37) and did not change significantly during the study period (P = 0.70 for trend). These visit rates were higher in patients aged <45 years (n = 62) and >or=75 years (n = 54) versus those aged 45-74 years (n = 21), in female (n = 37) versus male (n = 30) patients, in black (n = 40) vs. white (n = 25) patients, and in Hispanic (n = 21) versus non-Hispanic (n = 12) patients (all P < 0.001).Greater emphasis on intensive glycemic control has not resulted in increased emergency department visit rates for hypoglycemia. We identified demographic disparities, however, that merit further evaluation. The emergency department provides an important opportunity for epidemiologic study and intervention for severe hypoglycemia.
Mechanistic Links Between Na <sup>+</sup> Channel (SCN5A) Mutations and Impaired Cardiac Pacemaking in Sick Sinus Syndrome
Authors: Timothy D. Butters, Oleg V. Aslanidi, Shin Inada, Mark R. Boyett, Jules C. Hancox, Ming Lei, Henggui Zhang
Journal: Circulation Research (2010)

Familial sick sinus syndrome (SSS) has been linked to loss-of-function mutations of the SCN5A gene, which result in decreased inward Na(+) current, I(Na). However, the functional role of I(Na) in cardiac pacemaking is controversial, and mechanistic links between mutations and sinus node dysfunction in SSS are unclear.To determine mechanisms by which the SCN5A mutations impair cardiac pacemaking.Action potential (AP) models for rabbit sinoatrial node (SAN) cells were modified to incorporate experimentally reported I(Na) changes induced by 2 groups of SCN5A gene mutations (affecting the activation and inactivation of I(Na), respectively). The cell models were incorporated into an anatomically detailed 2D model of the intact SAN-atrium. Effects of the mutations and vagal nerve activity on cardiac pacemaking at the single-cell and tissue levels were studied. Multielectrode extracellular potential recordings of activation pattern from intact SAN-atrium preparations were performed to test predictions of the models. At the single-cell level, the mutations slowed down pacemaking rates in peripheral, but not in central SAN cells that control the heart rhythm. However, in tissue simulations, the mutations not only slowed down pacemaking, but also compromised AP conduction across the SAN-atrium, leading to a possible SAN exit block or sinus arrest, the major features of SSS. Simulated vagal nerve activity amplified the bradycardiac effects of the mutations. Two groups of SCN5A mutations showed subtle differences in impairing the ability of the SAN to drive the surrounding atrium, primarily attributable to their differential effects on atrial excitability and conduction safety. Experimental data with tetrodotoxin and carbachol confirmed the simulation outcomes.Our study substantiates the causative link between SCN5A gene mutations and SSS and illustrates mechanisms by which the mutations impair the driving ability of the SAN.
A biomechanical basis for tears of the human acetabular labrum
Authors: C D Smith, S Masouros, A M Hill, A A Amis, A M J Bull
Journal: British Journal of Sports Medicine (2008)

Acetabular labral tears predominantly affect young patients and are a source of hip pain in the athlete. Four causes of the initiation of labral tears have been proposed; trauma, hypolaxity of the anterior capsule, dysplasia and bony impingement. A further cause could be reduced biomechanical properties in the area most susceptible to tears. However, no work has defined these properties.32 compressive and 32 tensile test samples were harvested from fresh-frozen cadaveric acetabula. The labrum was divided into eight areas to allow comparison around its circumference. Semiconfined compressive testing and tensile testing were performed at a displacement rate of 10 mm/min in a controlled environment of 100% humidity at 37 (SD 1) degrees C.Cadaveric study.The mean compressive stiffness was 31.75 (SD 16.7) MPa, and the mean tensile elastic modulus was 24.7 (SD 10.8) MPa. The anterosuperior region had a significantly lower compressive elastic modulus than either of the posterior quadrants (p<0.05) and a significantly lower tensile modulus to the anterioinferior area (p<0.05).The biomechanical properties in the anterosuperior region may be a contributing factor to the initiation of labral tears.
Abstract A99: DCQ is a hypoxia-activated quinoxaline 1,4-dioxide that reduces breast cancer metastasis
Authors: Khaled I. Ghattass, Sally El Sitt, Kazem Zibara, Makhlouf MJ Haddadin, Marwan El-Sabban, Hala Ghali-Muhtasib
Journal: Cancer Research (2013)

Abstract Although tumor hypoxia is associated with the complex processes of tumor metastasis and resistance, and poses significant challenges against traditional cancer treatments, it provides a target for therapy by bioreductive drugs with enhanced cytotoxic activity in the reduced microenvironment of tumors. We identified a potent synthetic quinoxaline di-N-oxide (DCQ) which preferentially targets hypoxic tumors. Here we show that DCQ: 1) Reduces the viability of breast cancer cell lines (MDA-MB-231, MCF-7), 2) Induces reactive oxygen species (ROS)-dependent p53-independent apoptosis, 3) Inhibits the accumulation of hypoxia inducible factor (HIF-1α) via distinct mechanisms in the two cell lines and 4) Significantly reduces hypoxia-induced invasion of breast cancer cell lines in vitro and in vivo. DCQ-induced ROS was associated with increased DNA damage in MDA-MB-231 and MCF-7 cells. The inhibition of HIF-1α accumulation in MCF-7 was in part via the activation of p53 and was accompanied by a decrease in the levels of phosphorylated mTOR, indicating that DCQ-induced reduction of HIF-1α is possibly occurring at the translational level of the protein. HIF-1α reduction was associated with a decrease in p21 and a reversal of the hypoxia-induced VEGF secretion and invasion, which are key processes in tumor metastasis. In MDA-MB-231 cells; however, DCQ reduced HIF-1α through proteasomal degradation, which was accompanied by a reduction of TWIST, a major player in epithelial to mesenchymal transition (EMT). The inhibitory effect of DCQ on hypoxia induced breast cancer invasion was validated in the xenograft model of subdermally injected MDA-MB-231 cells in immune-compromised mice. DCQ significantly increased the survival rate of treated animals. This increase was associated with a reduction of the metastatic dissemination of breast cancer cells into the liver and lungs of DCQ treated mice. Citation Format: Khaled I. Ghattass, Sally El Sitt, Kazem Zibara, Makhlouf MJ Haddadin, Marwan El-Sabban, Hala Ghali-Muhtasib. DCQ is a hypoxia-activated quinoxaline 1,4-dioxide that reduces breast cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A99.
TRANSFORMATION REACTIONS WITH TWO NON-ALLELIC R MUTANTS OF THE SAME STRAIN OF PNEUMOCOCCUS TYPE VIII
Authors: Colin M. Macleod, Marjorie R. Krauss
Journal: The Journal of Experimental Medicine (1956)

Two distinct R mutants of pneumococcus type VIIIS have been described in which the mutations leading to loss of type VIII polysaccharide production are non-allelic. A DNA extract prepared from either R strain restores the capacity to produce type VIII polysaccharide in the other strain. Autologous extracts are inert in this respect. DNA extracts from pneumococcus type IIS when applied to the two R mutants consistently yielded a high proportion of cells transformed to type VIIIS and relatively small numbers of type IIS cells. When extracts prepared from other encapsulated pneumococci, types IS, VIIS, XIVS, and XVIIIS, were applied to R mutant VIII-R1, a mixture of type VIIIS cells and cells corresponding to the type of the donor appeared, although the proportion of type VIIIS cells was not uniformly in excess. The same extracts applied to the second R mutant, VIII-R13, yielded transformed cells of the type of the donor only, or else transformation did not occur. Transforming extracts of a strain of pneumococcus type IIIS gave rise only to type IIIS pneumococci when applied to either strain. Type VIIIS pneumococci were never recovered from such interactions.
BLUE NAEVUS OF ORAL MUCOSA
Authors: W. BOGOMOLETZ
Journal: British Journal of Dermatology (1968)

Journal Article BLUE NAEVUS OF ORAL MUCOSA Get access W. BOGOMOLETZ W. BOGOMOLETZ Department of Morbid Anatomy, Westminster Hospital School of Medicine, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 80, Issue 9, 1 September 1968, Pages 611–613, https://doi.org/10.1111/j.1365-2133.1968.tb12361.x Published: 01 September 1968 Article history Accepted: 29 April 1968 Published: 01 September 1968