tbuckley/cabot-search huggingface dataset:
Atrial pacing stimulates secretion of atrial natriuretic polypeptide without elevation of atrial pressure in awake dogs with experimental complete atrioventricular block.
Authors: K Nishimura, T Ban, Y Saito, K Nakao, H Imura
Journal: Circulation Research (1990)

To clarify whether or not tachycardia stimulates the secretion of atrial natriuretic polypeptide (ANP) without elevation of atrial pressure, we examined the effects of atrial pacing on ANP secretion in awake dogs with normal sinus rhythm and with complete atrioventricular block (CAVB), which was produced surgically by heat cauterization of His' bundle. In four dogs with normal sinus rhythm, atrial pacing increased the atrial rate from 146 +/- 20 to 260 +/- 10 beats/min, with marked elevation of right atrial pressure (from 0.2 +/- 0.1 to 3.9 +/- 0.8 mm Hg) and left atrial pressure (from 0.2 +/- 0.1 to 8.6 +/- 2.8 mm Hg). Along with the hemodynamic changes, the ANP level in plasma obtained from the coronary sinus was increased from 405 +/- 99 to 849 +/- 199 pg/ml (p less than 0.01). In five dogs with CAVB, the ANP level was also significantly increased from 730 +/- 82 to 1,137 +/- 35 pg/ml (p less than 0.01) by rapid atrial pacing (from 164 +/- 20 to 317 +/- 30 beats/min) in spite of the lack of any appreciable changes in either left or right atrial pressure. Furthermore, in the CAVB group, while the ventricular rate was increased by ventricular pacing from 52 +/- 5 to 146 +/- 16 beats/min, atrial pacing was performed simultaneously without atrioventricular (A-V) sequential form. Even under this condition, the ANP level was increased from 480 +/- 172 to 626 +/- 223 pg/ml (p less than 0.05) without any substantial changes in atrial pressure. Such effects of rapid atrial pacing on ANP secretion were suppressed after infusion of autonomic blocking agents.(ABSTRACT TRUNCATED AT 250 WORDS)
INDIVIDUAL BLOOD DIFFERENCES IN MEXICAN INDIANS, WITH SPECIAL REFERENCE TO THE Rh BLOOD TYPES AND Hr FACTOR
Authors: Alexander S. Wiener, J. Preciado Zepeda, Eve B. Sonn, H. R. Polivka
Journal: The Journal of Experimental Medicine (1945)

98 Mexican Indians were tested for the blood properties A-B-O, A(1)-A(2), M-N, P, Rh'-Rh''-Rh(0)-rh, and Hr. Of the 98 Indians, 90.8 per cent belonged to group 0, 6.1 per cent belonged to A(1), and 3.1 per cent to group B. There were 61.2 per cent of type M, 3.1 per cent of type N, and 35.7 per cent of type MN. Of the 95 Mexican Indians tested with anti-P serum, 21.1 per cent were found to lack the P agglutinogen. In tests for the Rh blood types, 48.0 per cent of the Indians were found to belong to type Rh(1), 9.2 per cent to type Rh(2), 41.8 per cent to type Rh(1)Rh(2), and 1 per cent to type Rh(0). There were no bloods giving intermediate reactions. Of the 95 Indians tested for the Hr factor 44.2 per cent were found to lack this property. The reactions for the Rh blood types and Hr factor were correlated with each other and the results supported the conclusion of Race et al. that in addition to the six standard allelic genes and the so called intermediate genes, there is one or possibly two genes having the property of determining agglutinogens which react with anti-Rh' and anti-Rh'' sera, but not with anti-Hr serum. This gene (or genes) appears to be relatively common among Mexican Indians (approximately 3.3 per cent) in contrast to its rareness in white individuals.
A PLEA FOR THE USE OF TUBERCULIN WITHIN AND WITHOUT SANATORIUMS
Authors: W. C. Wilkinson
Journal: BMJ (1907)

IIUNE 1, IS Professor of Helminthology, for the unselfish way in which he, at the ex-pense of much time and patience, initiated me into those special methods of work and thought that in his hands have already so greatly enriched helmintho- logical literature.
The Cyclin-Dependent Kinase Pathway Moves Forward
Authors: Karin E. Bornfeldt
Journal: Circulation Research (2003)

he cell cycle of mammalian cells is divided into four phases: G 1 (first gap), S (DNA synthesis), G 2 (second gap), and M (mitosis).Quiescent cells that have not entered the cell cycle are referred to as being in G 0 .Progression through the cell cycle requires the activation of cyclindependent kinases (CDKs).CDK activation is dependent on the association of the CDK with a cyclin regulatory subunit.Cyclin D/CDK4, cyclin D/CDK6, and cyclin E/CDK2 regulate transition through G 1 , cyclin A/CDK2 regulates S phase transition, and cyclin A/CDK2 and cyclin B/CDK2 regulate G 2 /M transition, 1 as shown by the Figure .The activity of CDKs is also regulated by endogenous CDK inhibitors (CKIs) in the cyclin/CDK complex 1 (Figure).Two families of CKIs have been characterized according to their structures and CDK targets.Kip/Cip proteins (p21 Cip1 , p27 Kip1 , and p57 Kip2 ), which bind to both cyclin and CDK subunits, inhibit cyclin E-and A-dependent kinases but act as positive regulators of cyclin D-dependent kinases.The INK family of proteins (p16 INKa , p15 INKb , p18 INKc , and p19 INKd ) exclusively binds to and inhibits CDK4 and CDK6. 1 Initiation of the cell cycle occurs when a quiescent cell (in G 0 ) is stimulated with appropriate mitogenic stimulus.This event induces expression of D-type cyclins that bind to CDK4 and CDK6, and then enter the nucleus.Active cyclin D-dependent kinases phosphorylate the retinoblastoma protein (Rb) in mid-G 1 . 1 Rb is then phosphorylated on additional sites by the cyclin E/CDK2 complex, and this event leads to disruption of Rb association with the transcription factor complex E2F, release of active E2F, and subsequent transcription of genes necessary for DNA synthesis, such as DNA polymerase ␣ and thymidine kinase. 2Cyclin A-and B-dependent kinases maintain Rb in a hyperphosphorylated form during S, G 2 , and M. 1 How Do Processes Involved in the Cell Cycle Lead to the Generation of Cell Movement?It appears that the maximal potential for a given cell, including a SMC, to migrate coincides with the mid-late G 1
Molecular forms of atrial natriuretic factor in normal and failing human myocardium.
Authors: R J Rodeheffer, M Naruse, J B Atkinson, K Naruse, J C Burnett, W H Merrill, W H Frist, H Demura, T Inagami
Journal: Circulation (1993)

BACKGROUND Atrial natriuretic factor (ANF) is produced by myocardial tissue, and the plasma ANF concentration is known to be elevated in congestive heart failure (CHF). Data from animal models indicate that myocardial concentrations of ANF are depleted in CHF, and this has given rise to the hypothesis that CHF is characterized by depletion of stored ANF. To date, the molecular forms of ANF and their concentrations in atrial and ventricular myocardium remain poorly characterized in the normal and the failing human heart. METHODS AND RESULTS We measured ANF concentrations in fresh tissue from failing human hearts explanted at the time of cardiac transplantation and from organ donors whose normal hearts could not be used for transplantation. We determined total ANF and alpha, beta, and gamma ANF concentrations in the right and left atrial appendages, atrial free walls, and ventricles. In normal hearts, ANF concentration in the atrial appendages was 40-fold higher than ANF in the rest of the atrial free wall and in the ventricles. In the failing hearts, atrial appendage ANF concentrations increased 5- to 10-fold, and atrial free wall ANF concentrations increased 200-fold. Analysis of molecular forms of ANF demonstrated significant increases in the gamma and beta forms in the left atrial appendage of failing hearts. alpha, beta, and gamma ANF forms were also significantly increased in right and left atrial free wall tissue from failing hearts. In addition, failing hearts were characterized by absolute and relative increases in the precursor form gamma ANF. CONCLUSIONS These data from fresh tissues suggest that cardiac ANF stores are not decreased in severe CHF in humans; rather, chronic CHF is characterized by marked increases in atrial ANF tissue concentrations, particularly the beta and gamma ANF forms. These findings are consistent with intracellular accumulation of precursor ANF forms in severe chronic human CHF.
COPD: an inhaled corticosteroid-resistant, oral corticosteroid-responsive condition
Authors: S. Saha
Journal: European Respiratory Journal (2006)

with good AQI according to US-EPA (,12.5 mg?m -3 ) in the car parking area and inside the Bella Center, with a level of 6.0¡1.7 and 3.0¡0.9mg?m -3 , respectively.Peak values were 12.5 mg?m -3 and 12.0 mg?m -3 , respectively.However, outside in front of the Bella Center with smokers, mean PM2.5 was 17.8¡7.5mg?m -3 with a peak of 98.9 mg?m -3 (p,0.03, as compared with inside the venue), which is a step down in AQI.PM2.5 along the motorway was only 4.6¡0.7 mg?m -3 with a peak value of 8.7 mg?m -3 .Inside the restaurant, high concentrations of PM2.5 were found (165.1¡8.5 mg?m -3 ) with a peak value of 372.2 mg?m -3 , with a ''very unhealthy'' AQI.Official outdoor PM2.5 mean¡SEM recorded in the town for the time interval of all the measurements was 5.7¡0.4mg?m -3 .Overall, mean values observed with smokers in front of the Bella Center and inside the restaurant were significantly higher than the outdoor parking place, indoor Bella Center, motorway and Copenhagen outdoor official data (p,0.05and p,0.001, respectively).
Independent regulation of IgM, IgD, and Ia antigen expression in cultured immature B lymphocytes.
Authors: J R Dasch, P P Jones
Journal: The Journal of Experimental Medicine (1986)

Long-term cultured bone marrow cells were characterized with respect to a number of B and pre-B cell markers. Cells expressing ThB, B-220, and IgM were found within cultures set up according to the procedure of Whitlock and Witte. This culture system was modified by placing sorted pre-B cells (ThB+, IgM-) from bone marrow in culture with previously-established bone marrow adherent layers. These cultures commenced growth without the lag associated with the Whitlock cultures. These cultured nonadherent cells show a high frequency of IgM+ cells, but do not express either IgD or Ia, and we refer to them as immature B cells. Cells with a similar phenotype (IgM+, Ia-, IgD-) are found within the spleens of young but not adult mice. The phorbol ester PMA induces expression of IgD on the cultured immature B cells, but has no effect on Ia expression. This suggests that the processing of H chain RNA transcripts may be affected by protein kinase C. These results demonstrate that the appearance of IgM, IgD, and Ia are independently controlled in long-term cultured B-lineage cells.
AP-1 and STAT-1 decoy oligodeoxynucleotides attenuate transplant vasculopathy in rat cardiac allografts
Authors: T. H.W. Stadlbauer, A. H. Wagner, H. Holschermann, S. Fiedel, H. Fingerhuth, H. Tillmanns, R. M. Bohle, M. Hecker
Journal: Cardiovascular Research (2008)

AimsCardiac allograft vasculopathy (CAV) continues to be an unsolved clinical problem requiring the development of new therapeutic strategies. We have previously demonstrated that ex vivo donor allograft treatment with decoy oligodeoxynucleotides (ODN) targeting the transcription factors, activator protein-1 (AP-1) or signal transducer and activator of transcription-1 (STAT-1), delays acute rejection and prolongs cardiac allograft survival. Here, we investigated whether this treatment regime also prevents the occurrence of CAV in a fully allogeneic rat heart transplantation model.
Acute Asthma among Pregnant Women Presenting to the Emergency Department
Authors: RITA K. CYDULKA, CHARLES L. EMERMAN, DONALD SCHREIBER, KARIN H. MOLANDER, PRESCOTT G. WOODRUFF, CARLOS A. CAMARGO
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Asthma complicates up to 4% of pregnancies. Our objective was to compare emergency department (ED) visits for acute asthma among pregnant versus nonpregnant women. We performed a prospective cohort study, as part of the Multicenter Asthma Research Collaboration. ED patients who presented with acute asthma underwent a structured interview in the ED, and another by telephone 2 wk later. The study was performed at 36 EDs in 18 states. A total of 51 pregnant women and 500 nonpregnant women, age 18 to 39, were available for analysis. Pregnant women did not differ from nonpregnant women by duration of asthma symptoms (median: 0.75 versus 0.75 d, p = 0.57) or initial peak expiratory flow rate (PEFR) (51% versus 53% of predicted, p = 0.52). Despite this similarity, only 44% of pregnant women were treated with corticosteroids in the ED compared with 66% of nonpregnant women (p = 0.002). Pregnant women were equally likely to be admitted (24% versus 21%, p = 0.61) but less likely to be prescribed corticosteroids if sent home (38% versus 64%, p = 0.002). At 2-wk follow-up, pregnant women were 2.9 times more likely to report an ongoing exacerbation (95% CI, 1.2 to 6.8). Among women presenting to the ED with acute asthma, pregnant asthmatics are less likely to receive appropriate treatment with corticosteroids.
CCR7 Signals Are Essential for Cortex–Medulla Migration of Developing Thymocytes
Authors: Tomoo Ueno, Fumi Saito, Daniel H.D. Gray, Sachiyo Kuse, Kunio Hieshima, Hideki Nakano, Terutaka Kakiuchi, Martin Lipp, Richard L. Boyd, Yousuke Takahama
Journal: The Journal of Experimental Medicine (2004)

Upon TCR-mediated positive selection, developing thymocytes relocate within the thymus from the cortex to the medulla for further differentiation and selection. However, it is unknown how this cortex–medulla migration of thymocytes is controlled and how it controls T cell development. Here we show that in mice deficient for CCR7 or its ligands mature single-positive thymocytes are arrested in the cortex and do not accumulate in the medulla. These mutant mice are defective in forming the medullary region of the thymus. Thymic export of T cells in these mice is compromised during the neonatal period but not in adulthood. Thymocytes in these mice show no defects in maturation, survival, and negative selection to ubiquitous antigens. TCR engagement of immature cortical thymocytes elevates the cell surface expression of CCR7. These results indicate that CCR7 signals are essential for the migration of positively selected thymocytes from the cortex to the medulla. CCR7-dependent cortex–medulla migration of thymocytes plays a crucial role in medulla formation and neonatal T cell export but is not essential for maturation, survival, negative selection, and adult export of thymocytes.
EGF Receptor Deletion in Podocytes Attenuates Diabetic Nephropathy
Authors: Jianchun Chen, Jian-Kang Chen, Raymond C. Harris
Journal: Journal of the American Society of Nephrology (2014)

The generation of reactive oxygen species (ROS), particularly superoxide, by damaged or dysfunctional mitochondria has been postulated to be an initiating event in the development of diabetes complications. The glomerulus is a primary site of diabetic injury, and podocyte injury is a classic hallmark of diabetic glomerular lesions. In streptozotocin-induced type 1 diabetes, podocyte-specific EGF receptor (EGFR) knockout mice (EGFR(podKO)) and their wild-type (WT) littermates had similar levels of hyperglycemia and polyuria, but EGFR(podKO) mice had significantly less albuminuria and less podocyte loss compared with WT diabetic mice. Furthermore, EGFR(podKO) diabetic mice had less TGF-β1 expression, Smad2/3 phosphorylation, and glomerular fibronectin deposition. Immunoblotting of isolated glomerular lysates revealed that the upregulation of cleaved caspase 3 and downregulation of Bcl2 in WT diabetic mice were attenuated in EGFR(podKO) diabetic mice. Administration of the SOD mimetic mito-tempol or the NADPH oxidase inhibitor apocynin attenuated the upregulation of p-c-Src, p-EGFR, p-ERK1/2, p-Smad2/3, and TGF-β1 expression and prevented the alteration of cleaved caspase 3 and Bcl2 expression in glomeruli of WT diabetic mice. High-glucose treatment of cultured mouse podocytes induced similar alterations in the production of ROS; phosphorylation of c-Src, EGFR, and Smad2/3; and expression of TGF-β1, cleaved caspase 3, and Bcl2. These alterations were inhibited by treatment with mito-tempol or apocynin or by inhibiting EGFR expression or activity. Thus, results of our studies utilizing mice with podocyte-specific EGFR deletion demonstrate that EGFR activation has a major role in activating pathways that mediate podocyte injury and loss in diabetic nephropathy.
A new consensus error grid to evaluate the clinical significance of inaccuracies in the measurement of blood glucose.
Authors: J L Parkes, S L Slatin, S Pardo, B H Ginsberg
Journal: Diabetes Care (2000)

OBJECTIVE: The objectives of this study were 1) to construct new error grids (EGs) for blood glucose (BG) self-monitoring by using the expertise of a large panel of clinicians and 2) to use the new EGs to evaluate the accuracy of BG measurements made by patients. RESEARCH DESIGN AND METHODS: To construct new EGs for type 1 and type 2 diabetic patients, a total of 100 experts of diabetes were asked to assign any error in BG measurement to 1 of 5 risk categories. We used these EGs to evaluate the accuracy of self-monitoring of blood glucose (SMBG) levels in 152 diabetic patients. The SMBG data were used to compare the new type 1 diabetes EG with a traditional EG. RESULTS: Both the type 1 and type 2 diabetes EGs divide the risk plane into 8 concentric zones with no discontinuities. The new EGs are similar to each other, but they differ from the traditional EG in several significant ways. When used to evaluate a data set of measurements made by a sample of patients experienced in SMBG, the new type 1 diabetes EG rated 98.6% of their measurements as clinically acceptable, compared with 95% for the traditional EG. CONCLUSIONS: The consensus EGs furnish a new tool for evaluating errors in the measurement of BG for patients with type 1 and type 2 diabetes.
STUDIES ON PSEUDORABIES (INFECTIOUS BULBAR PARALYSIS, MAD ITCH
Authors: E. Weston Hurst
Journal: The Journal of Experimental Medicine (1936)

In the monkey (M. mulatto) the virus of pseudorabies, pantropic in the rabbit, behaves as a strict neurotrope. Infection, usually fatal, readily follows intracerebral and intracisternal inoculation of rabbit virus, and often intrasciatic inoculation; the symptomatology of the ensuing disease is described. In a limited number of experiments no infection resulted from intradermal, intramuscular or intravenous inoculation. Nerve and glial cells are primarily attacked by the virus, but no cytological or other evidence of susceptibility of non-nervous tissue or of growth of virus outside the nervous system was obtained. Certain cortical areas, of which the principal are the pyriform area, cornu Ammonis, island of Reil, lower lip of the Sylvian fissure and basal surface of the frontal lobe, are affected far more severely than are other parts of the nervous axis; the reasons for this elective distribution of the most severe lesions, seen alike after intracerebral and intrasciatic inoculation and analogous perhaps to that in poliomyelitis and louping-ill, are not obvious. Other areas of the nervous system are relatively insusceptible to the action of the virus. Cases showing clinically only a febrile reaction without definite nervous symptoms may later exhibit marked residual lesions at the sites of election. The blood and cerebrospinal fluid play no apparent rôle in disseminating the virus, which, after intrasciatic inoculation, spreads upwards by the nervous path. Some suggestion was received from the experiments that in monkeys possessed of immunity to B virus (Sabin and Wright, 1934) pseudorabic infection is less likely to prove fatal than in animals not so immune, but the observations made were insufficiently numerous to be of statistical value. The sera of 6 out of 26 monkeys were found to contain antibodies neutralising B virus; these 6 monkeys were all included in one batch of 7 received at one time from the dealer.
Characterization of Human CD8+ T Cells Reactive with <i>Mycobacterium tuberculosis</i>–infected Antigen-presenting Cells
Authors: David M. Lewinsohn, Mark R. Alderson, Andria L. Briden, Stanley R. Riddell, Steven G. Reed, Kenneth H. Grabstein
Journal: The Journal of Experimental Medicine (1998)

Previous studies in murine models, including those using the β2 microglobulin knockout mouse, have suggested an important role for CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). At present, little is understood about these cells in the human immune response to tuberculosis. This report demonstrates the existence of human Mtb-reactive CD8+ T cells. These cells are present preferentially in persons infected with Mtb and produce interferon γ in response to stimulation with Mtb-infected target cells. Recognition of Mtb-infected cells by these CD8+ T cells is restricted neither by the major histocompatibility complex (MHC) class I A, B, or C alleles nor by CD1, although it is inhibited by anti–MHC class I antibody. The Mtb-specific CD8+ T cells recognize an antigen which is generated in the proteasome, but which does not require transport through the Golgi-ER. The data suggest the possible use of nonpolymorphic MHC class Ib antigen presenting structures other than CD1.
The molecular profile of microglia under the influence of glioma
Authors: W. Li, M. B. Graeber
Journal: Neuro-Oncology (2012)

Microglia, which contribute substantially to the tumor mass of glioblastoma, have been shown to play an important role in glioma growth and invasion. While a large number of experimental studies on functional attributes of microglia in glioma provide evidence for their tumor-supporting roles, there also exist hints in support of their anti-tumor properties. Microglial activities during glioma progression seem multifaceted. They have been attributed to the receptors expressed on the microglia surface, to glioma-derived molecules that have an effect on microglia, and to the molecules released by microglia in response to their environment under glioma control, which can have autocrine effects. In this paper, the microglia and glioma literature is reviewed. We provide a synopsis of the molecular profile of microglia under the influence of glioma in order to help establish a rational basis for their potential therapeutic use. The ability of microglia precursors to cross the blood-brain barrier makes them an attractive target for the development of novel cell-based treatments of malignant glioma.
Are We Ready for Online Tools in Decision Making for <i>BRCA1/2</i> Mutation Carriers?
Authors: D. Gareth Evans, Anthony Howell
Journal: Journal of Clinical Oncology (2012)

mutationcarriersregard-ingwhenandwhethertoundergoriskreducingbreastandorovariansurgeryiscomplexandinvolvesnotonlythedesiretostayalivelonger,but to avoid the diagnosis of breast and ovarian cancer itself. Theseconsiderationsarebalancedagainstthedesireformostwomentohavechildren,whichinmodernwesternsocietyisoftenatalaterage,aswellas the impact of bilateral salpingo-oophorectomy (BSO) in causingearly menopause with its attendant symptoms, increase in heart dis-easeandosteoporosisrisk,andforsomewomenalossofsexualityandgender identity.