tbuckley/cabot-search huggingface dataset:
Na+-dependent and -independent Cl?/HCO3? exchange mediate cellular HCO3? transport in cultured human intrahepatic bile duct cells
Authors: M Strazzabosco, R Joplin, A Zsembery, L Wallace, C Spirli, L Fabris, A Granato, A Rossanese, C Poci, J M Neuberger, L Okolicsanyi, G Crepaldi
Journal: Hepatology (1997)

Biliary epithelial cells (cholangiocytes) modulate bile fluidity and alkalinity absorbing and/or secreting fluid and electrolytes, particularly HCO 3 − and Cl − . Mechanisms responsible for transepithelial H + /HCO 3 − secretion in human cholangiocytes are largely unknown. Human cholangiocytes isolated by enzymatic digestion and immunomagnetic purification from normal liver tissue obtained from reduced grafts used for pediatric liver transplantation were cultured in the presence of human hepatocyte growth factor. Maintenance of cholangiocyte phenotypic features was assessed using markers such as cytokeratin 19, γ-glutamyltranspeptidase, vimentin, factor VIII-related antigen, desmin, epithelial membrane antigen (EMA), and human epithelial antigen (HEA) 125. Intracellular pH (pHi) transients were measured microfluorimetrically 2′7′-Bis(2-carboxyethyl)-5,6, carboxyfluorescein-acetossimethylester (BCECF). In the absence of HCO 3 − , pHi recovery from an intracellular acid load (ammonia pre-pulse technique) was Na + -dependent and amiloride-inhibitable. No Na + -independent recovery was recorded even after stimulation with agents raising intracellular cyclic adenosine monophosphate (cAMP) concentrations. In the presence of HCO 3 − , recovery from an intracellular acid load required Na+, but was only partly inhibited by amiloride. In these conditions H+ extrusion was inhibited by 4,4-diisothiocyan atostilben-2,2-disulfonic acid (DIDS) and by intracellular Cl-depletion. Acute removal of extracellular Cl induced a pHi alkalinization that was inhibited by DIDS. pHi recovery from an intracellular alkaline load (isohydric CO2 changes) was Cl − -dependent and DIDS-inhibitable. Administration of agents raising intracellular cAMP concentrations increased both Na + -dependent and Na + -independent Cl-/HCO-3 exchange activity. Stimulation of Cl-/HCO 3 − exchange activity was not prevented by the Cl-channel inhibitor 5′-nitro-2(2)-phenylpropyl-amino-benzoate(NPPB). In conclusion, human cholangiocytes possess two acid extruders (Na + /H + exchanger and Na + -dependent Cl-/HCO 3 − exchange) and an acid loader (Cl-/HCO 3 − exchange), whereas no evidence was found for cAMP activated H + -ATPase. Bicarbonate influx is thus mainly mediated by Na-dependent Cl − /HCO 3 − exchange, whereas Na + :HCO 3 − cotransport is not active in the physiological range of pHi. Stimulation of Na + -independent Cl − /HCO 3 − exchanger by cAMP does not require activation of Cl − conductances. These mechanisms may underlay hormone-regulated biliary HCO 3 − secretion in the human biliary tree.
Isolation and Characterization of Tumorigenic, Stem-like Neural Precursors from Human Glioblastoma
Authors: Rossella Galli, Elena Binda, Ugo Orfanelli, Barbara Cipelletti, Angela Gritti, Simona De Vitis, Roberta Fiocco, Chiara Foroni, Francesco Dimeco, Angelo Vescovi
Journal: Cancer Research (2004)

Abstract Transformed stem cells have been isolated from some human cancers. We report that, unlike other brain cancers, the lethal glioblastoma multiforme contains neural precursors endowed with all of the critical features expected from neural stem cells. Similar, yet not identical, to their normal neural stem cell counterpart, these precursors emerge as unipotent (astroglial) in vivo and multipotent (neuronal-astroglial-oligodendroglial) in culture. More importantly, these cells can act as tumor-founding cells down to the clonal level and can establish tumors that closely resemble the main histologic, cytologic, and architectural features of the human disease, even when challenged through serial transplantation. Thus, cells possessing all of the characteristics expected from tumor neural stem cells seem to be involved in the growth and recurrence of adult human glioblastomas multiforme.
Death and Cremation Certificates
Authors: C. A. Birch
Journal: BMJ (1964)

BRDITAILSOHNAL 841 distribution was compared with that found by Hervey et al.2 in 141,774 consecutive white blood donors to the American Red Cross and is shown in the Table .Statistical evaluation of these results showed that there was no significant differ- ences in the per cent.blood-group distribution, either overall or when blood groups 0 and A were examined separately from groups B and AB (X'=0.02;, P>0.05) between the controls and the patients with acute appen- dicitis.
Platelet Glycoprotein Ibα HPA-2 Met/VNTR B Haplotype as a Genetic Predictor of Myocardial Infarction and Sudden Cardiac Death
Authors: Jussi Mikkelsson, Markus Perola, Antti Penttilä, Pekka J. Karhunen
Journal: Circulation (2001)

Background — Sudden cardiac death (SCD) is one of the leading manifestations of coronary heart disease in early middle age. Platelet glycoprotein (GP) Ib-IX-V receptor complexes play a key role in the initial adhesion of platelets to collagen during the formation of a coronary thrombus. The HPA-2 (Thr145 Met) and VNTR polymorphisms of the gene for GP Ibα have been studied previously in hospitalized patients with acute coronary syndromes. The significance of these polymorphisms in victims of sudden cardiac death is not known. Methods and Results — The association of these 2 polymorphisms with coronary atherosclerosis, coronary artery stenosis, coronary thrombosis, myocardial infarction (MI), and SCD was studied in the Helsinki Sudden Death Study, which comprised 2 large autopsy series, collected 10 years apart during 1981 to 1982 and 1991 to 1992, of 700 middle-aged white Finnish men who suffered sudden or violent out-of-hospital death. The 2 polymorphisms showed an almost complete linkage disequilibrium. Men with acute MI (n=80) and coronary thrombosis (n=65) were more likely to be carriers of the HPA-2 Met allele (OR 2.0 and 2.6, respectively, P &lt;0.005 for both) than were control subjects who died of noncardiac causes (n=367). In men &lt;55 years old, the Met allele was overrepresented (OR 2.2) among victims of SCD (n=98) compared with control subjects (n=249). In men &lt;55 years old, 17 of 29 men with acute MI (58.6%) and 16 of 23 men with coronary thrombosis (69.6%) were carriers of the HPA-2 Met allele compared with the 49 of 249 (19.7%) who had died of noncardiac causes (ORs 5.6 and 9.2, respectively). Similar associations were observed in the separate analyses of both autopsy series. Conclusions — Our results suggest that the HPA-2 Met/VNTR B haplotype of the platelet von Willebrand factor and thrombin receptor protein GP Ib-V-IX may be considered to be a major risk factor of coronary thrombosis, fatal MI, and SCD in early middle age.
Peripheral Venous and Arteriolar Responses to Infusions of Angiotensin in Normal and Hypertensive Subjects
Authors: J. EDWIN WOOD
Journal: Circulation Research (1961)

The distensibility of the peripheral veins of the hypertensive subject is normal, that is, there is no evidence of peripheral venoconstriction, despite the excessive arteriolar constriction. The forearm veins of hypertensive patients respond to pooling of blood in the upright position to a lesser degree than do veins of normotensive individuals, indicating a lesser degree of smypathetic nervous activity in response to this stimulus. The peripheral veins of hypertensive subjects constrict normally in response to an infusion of norepinephrine, indicating that failure of venoconstriction in any circumstance cannot be attributed to failure of the smooth muscle of the veins. Infusions of angiotensin produce constriction of the veins as well as the arterioles in normotensive individuals thus failing to mimic the naturally occurring state of essential hypertension. Infusions of angiotensin in hypertensive patients result in further arteriolar constriction and hypertension without concomitant venoconstriction. The results of these experiments suggest that peripheral venous responses of hypertensive subjects to angiotensin infusions may have been modified by previous exposure of these vessels to a material at least similar to angiotensin.
The nature of the renal adaptation to chronic hypocapnia
Authors: F. John Gennari, Marc B. Goldstein, William B. Schwartz
Journal: Journal of Clinical Investigation (1972)

Metabolic balance studies were carried out in normal dogs to define the renal mechanisms responsible for the adaptation to, and recovery from, chronic hypocapnia. A chronic reduction in arterial CO(2) tension (Pa(CO2)) of some 15 mm Hg was achieved by means of chronic exposure of the animals to 9% oxygen in an environmental chamber. The development of hypocapnia was associated with a marked suppression of net acid excretion which, together with a slight accumulation of organic acids, produced a reduction in plasma bicarbonate concentration (8 mEq/liter) that led to nearly full protection of extracellular pH (DeltaH(+) = - 2.5 nmoles/liter). When Pa(CO2) was returned to control levels, an augmentation of acid excretion restored plasma composition to normal after a brief period of "posthypocapneic metabolic acidosis."The changes in renal acid excretion during both adaptation and recovery were accomplished in a fashion notably different from that previously observed in chronic hypercapnia, being linked to changes in cation rather than chloride excretion. Thus, in dogs ingesting a normal NaCl diet, suppression of hydrogen ion excretion during adaptation to hypocapnia was associated with an increased excretion of sodium rather than with a retention of chloride. The fact that this loss of sodium occurred without a concomitant loss of potassium strongly suggests that the hypocapneic state specifically depressed distal sodium reabsorption; if distal sodium reabsorption had not been depressed, a reduction in proximal sodium reabsorption or a diminution in distal hydrogen ion secretion (or both) should have produced an increase in potassium excretion. The interpretation that chronic hypocapnia diminished sodium reabsorption was supported by the finding that when renal sodium avidity was enhanced by restriction of sodium intake, acid retention was accomplished by a loss of potassium rather than of sodium. The accompanying reduction in plasma bicarbonate concentration was slightly less than that observed in dogs ingesting a normal NaCl diet, a finding probably accounted for by a slight difference in the availability of cation for excretion under the two experimental circumstances. These findings, taken together with the observation that augmented acid excretion during recovery from hypocapnia is linked to cation retention, suggest that an adequate intake of cation during both adaptation and recovery from chronic hypocapnia may be critical to the physiologic regulation of acid-base equilibrium.
Decoration of T-independent antigen with ligands for CD22 and Siglec-G can suppress immunity and induce B cell tolerance in vivo
Authors: Bao Hoa Duong, Hua Tian, Takayuki Ota, Gladys Completo, Shoufa Han, José Luis Vela, Miyo Ota, Michael Kubitz, Nicolai Bovin, James C. Paulson, David Nemazee
Journal: The Journal of Experimental Medicine (2009)

Autoreactive B lymphocytes first encountering self-antigens in peripheral tissues are normally regulated by induction of anergy or apoptosis. According to the “two-signal” model, antigen recognition alone should render B cells tolerant unless T cell help or inflammatory signals such as lipopolysaccharide are provided. However, no such signals seem necessary for responses to T-independent type 2 (TI-2) antigens, which are multimeric antigens lacking T cell epitopes and Toll-like receptor ligands. How then do mature B cells avoid making a TI-2–like response to multimeric self-antigens? We present evidence that TI-2 antigens decorated with ligands of inhibitory sialic acid–binding Ig-like lectins (siglecs) are poorly immunogenic and can induce tolerance to subsequent challenge with immunogenic antigen. Two siglecs, CD22 and Siglec-G, contributed to tolerance induction, preventing plasma cell differentiation or survival. Although mutations in CD22 and its signaling machinery have been associated with dysregulated B cell development and autoantibody production, previous analyses failed to identify a tolerance defect in antigen-specific mutant B cells. Our results support a role for siglecs in B cell self-/nonself-discrimination, namely suppressing responses to self-associated antigens while permitting rapid “missing self”–responses to unsialylated multimeric antigens. The results suggest use of siglec ligand antigen constructs as an approach for inducing tolerance.
The Effects of Chronic Hypoxemia on Electrolyte and Acid—Base Equilibrium: An Examination of Normocapneic Hypoxemia and of the Influence of Hypoxemia on the Adaptation to Chronic Hypercapnia*
Authors: Daniel G. Sapir, David Z. Levine, William B. Schwartz
Journal: Journal of Clinical Investigation (1967)

We have carried out balance studies in normal dogs in order to appraise the effects of chronic hypoxemia on acid—base and electrolyte equilibrium. During the first phase of observation we produced a state of “pure” hypoxemia by reducing the oxygen concentration (utilizing nitrogen as a diluent) and by adding carbon dioxide to the environment in a concentration sufficient to keep arterial CO2 tension (PCO2) within normal limits. The data demonstrate that such a 9-day period of normocapneic hypoxemia has no effect on electrolyte excretion and is virtually without effect on plasma composition.
Dynamics of chromatin accessibility and gene regulation by MADS-domain transcription factors in flower development
Authors: Alice Pajoro, Pedro Madrigal, Jose M Muiño, José Tomás Matus, Jian Jin, Martin A Mecchia, Juan M Debernardi, Javier F Palatnik, Salma Balazadeh, Muhammad Arif, Diarmuid S Ó’Maoiléidigh, Frank Wellmer, Pawel Krajewski, José-Luis Riechmann, Gerco C Angenent, Kerstin Kaufmann
Journal: Genome biology (2014)

Abstract Background Development of eukaryotic organisms is controlled by transcription factors that trigger specific and global changes in gene expression programs. In plants, MADS-domain transcription factors act as master regulators of developmental switches and organ specification. However, the mechanisms by which these factors dynamically regulate the expression of their target genes at different developmental stages are still poorly understood. Results We characterized the relationship of chromatin accessibility, gene expression, and DNA binding of two MADS-domain proteins at different stages of Arabidopsis flower development. Dynamic changes in APETALA1 and SEPALLATA3 DNA binding correlated with changes in gene expression, and many of the target genes could be associated with the developmental stage in which they are transcriptionally controlled. We also observe dynamic changes in chromatin accessibility during flower development. Remarkably, DNA binding of APETALA1 and SEPALLATA3 is largely independent of the accessibility status of their binding regions and it can precede increases in DNA accessibility. These results suggest that APETALA1 and SEPALLATA3 may modulate chromatin accessibility, thereby facilitating access of other transcriptional regulators to their target genes. Conclusions Our findings indicate that different homeotic factors regulate partly overlapping, yet also distinctive sets of target genes in a partly stage-specific fashion. By combining the information from DNA-binding and gene expression data, we are able to propose models of stage-specific regulatory interactions, thereby addressing dynamics of regulatory networks throughout flower development. Furthermore, MADS-domain TFs may regulate gene expression by alternative strategies, one of which is modulation of chromatin accessibility.
Phenotypic and functional studies of leukocytes in human endometrium and endometriosis
Authors: R. Jones
Journal: Human Reproduction Update (1998)

The aetiology of endometriosis, a common and disabling disorder, is presently unknown, although immune dysfunction could allow ectopic endometrial fragments to survive outside the uterine cavity. These studies investigate the relationship between leukocyte populations, steroid hormone receptor expression, proliferative activity, bcl-2 expression and apoptosis in eutopic and ectopic endometrium from women with endometriosis or adenomyosis at different phases of the menstrual cycle. Significantly increased oestrogen receptor expression, bcl-2 expression and numbers of CD8+ leukocytes were found in ectopic compared with eutopic endometrium in endometriosis, and CD56+ endometrial granulated lymphocytes (eGLs) were significantly reduced in ectopic endometrium. Apoptotic cells were rarely found in control and subject endometria. In contrast with endometriosis, adenomyotic lesions showed identical steroid hormone receptor expression, proliferative activity, bcl-2 expression and leukocyte subpopulations to eutopic endometrium, indicating different aetiologies for these disorders. The unusual CD56+ CD16-eGLs present in large numbers in late secretory phase eutopic endometrium were highly purified (>98%) by immunomagnetic separation. Except for a negligible cytotoxic activity of eGLs from early proliferative samples, cytotoxic activity of eGLs from non-pregnant endometrium during the menstrual cycle was comparable with those in peripheral blood, predominantly CD56+ CD16+ natural killer cells. eGLs from non-pregnant endometrium and early pregnancy showed a variable proliferative response to 5 and 100 U/ml interleukin-2 over 48-h and 120-h time courses. eGLs are evidently functionally important in the eutopic endometrium. Their absence in endometriotic lesions together with increased CD+8 T cell numbers and increased oestrogen receptor and bcl-2 expression may have significant effects on the development and progression of endometriosis.
Scoring systems using chest radiographic features for the diagnosis of pulmonary tuberculosis in adults: a systematic review
Authors: Lancelot M. Pinto, Madhukar Pai, Keertan Dheda, Kevin Schwartzman, Dick Menzies, Karen R. Steingart
Journal: European Respiratory Journal (2012)

Chest radiography for the diagnosis of active pulmonary tuberculosis (PTB) is limited by poor specificity and reader inconsistency. Scoring systems have been employed successfully for improving the performance of chest radiography for various pulmonary diseases. We conducted a systematic review to assess the diagnostic accuracy and reproducibility of scoring systems for PTB. We searched multiple databases for studies that evaluated the accuracy and reproducibility of chest radiograph scoring systems for PTB. We summarised results for specific radiographic features and scoring systems associated with PTB. Where appropriate, we estimated pooled performance of similar studies using a random effects model. 13 studies were included in the review, nine of which were in low tuberculosis (TB) burden settings. No scoring system was based solely on radiographic findings. All studies used systems with various combinations of clinical and radiological features. 11 studies involved scoring systems that were used for making decisions concerning hospital respiratory isolation. None of the included studies reported data on intra- or inter-reporter reproducibility. Upper lobe infiltrates (pooled diagnostic OR 3.57, 95% CI 2.38–5.37, five studies) and cavities (diagnostic OR range 1.97–25.66, three studies) were significantly associated with PTB. Sensitivities of the scoring systems were high (median 96%, IQR 93–98%), but specificities were low (median 46%, IQR 35–50%). Chest radiograph scoring systems appear useful in ruling out PTB in hospitals, but their low specificity precludes ruling in PTB. There is a need to develop accurate scoring systems for people living with HIV and for outpatient settings, especially in high TB burden settings.
The next ten stories on antiviral drug discovery (part E): advents, advances, and adventures
Authors: Erik De Clercq
Journal: Medicinal Research Reviews (2009)

This review article presents the fifth part (part E) in the series of stories on antiviral drug discovery. The ten stories belonging to this fifth part are dealing with (i) aurintricarboxylic acid; (ii) alkenyldiarylmethanes; (iii) human immunodeficiency virus (HIV) integrase inhibitors; (iv) lens epithelium-derived growth factor as a potential target for HIV proviral DNA integration; (v) the status presens of neuraminidase inhibitors NAIs in the control of influenza virus infections; (vi) the status presens on respiratory syncytial virus inhibitors; (vii) tricyclic (1,N-2-ethenoguanine)-based acyclovir and ganciclovir derivatives; (viii) glycopeptide antibiotics as antivirals targeted at viral entry; (ix) the potential (off-label) use of cidofovir in the treatment of polyoma (JC and BK) virus infections; and (x) finally, thymidine phosphorylase as a target for both antiviral and anticancer agents.
Risk Factors for Abdominal Aortic Aneurysms
Authors: Signe Helene Forsdahl, Kulbir Singh, Steinar Solberg, Bjarne K. Jacobsen
Journal: Circulation (2009)

Abdominal aortic aneurysm is an asymptomatic condition with a high mortality rate related to rupture.In a cohort of 2035 men and 2310 women in Tromsø, Norway, who were 25 to 82 years old in 1994, the authors identified risk factors for incident abdominal aortic aneurysm over the next 7 years. The impact of smoking was studied in particular. Ultrasound examination was performed initially in 1994/1995 and repeated in 2001. There were 119 incident cases of abdominal aortic aneurysms (an incidence of 0.4% per year). Male sex and increasing age were strong risk factors. In addition, the following variables were significantly associated with increased abdominal aortic aneurysm incidence: Smoking (OR=13.72, 95% CI 6.12 to 30.78, comparing current smokers of > or =20 cigarettes/d with never-smokers), hypertension (OR=1.54, 95% CI 1.03 to 2.30), hypercholesterolemia (OR=2.11, 95% CI 1.23 to 3.64, comparing subjects with serum total cholesterol > or =7.55 mmol/L with those with total cholesterol <5.85 mmol/L), and low high-density lipoprotein cholesterol (OR=3.25, 95% CI 1.68 to 6.27, comparing subjects with high-density lipoprotein cholesterol <1.25 mmol/L with those with high-density lipoprotein > or =1.83 mmol/L). In addition, use of statins was associated with increased risk of abdominal aortic aneurysm (OR=3.77, 95% CI 1.45 to 9.81), but this was probably a marker of high risk of cardiovascular diseases.The results demonstrate strong associations between traditional atherosclerosis risk factors and the risk of incident abdominal aortic aneurysms.
Expression of an idiotype (Id-460) during in vivo anti-dinitrophenyl antibody responses. I. Mapping of genes for Id-460 expression to the variable region of immunoglobulin heavy-chain locus and to the variable region of immunoglobulin kappa-light-chain locus.
Authors: E A Dzierzak, C A Janeway, R W Rosenstein, P D Gottlieb
Journal: The Journal of Experimental Medicine (1980)

The genetic contro of the expression of an idiotype (Id-460) associated with the 2,4-dinitrophenyl (DNP)-binding BALB/c myeloma protein MOPC 460 was studied using congenic strains of mice. It was shown that the expression of high levels of Id-460 during secondary in vivo anti-DNP-ovalbumin responses was determined by genes governing immunoglobulin heavy-chain variable and kappa-light chain variable regions (V kappa). Appropriate alleles at both loci were required for the expression of Id-460. Genes in the major histocompatability complex and the X-linked immune deficiency gene found in strain CBA/N did not greatly affect Id-460 expression. The V kappa gene controlling Id-460 expression can be differentiated from Lyt-3, and it is the first instance in which expression of an idiotype subdivides the V kappa genes associated with the Lyt-3a allele. Although it is likely that the V kappa gene(s) involved are structural, the involvememt of a regulatory gene linked to the structural gene can not be excluded.