tbuckley/cabot-search huggingface dataset:
Translocation (3;21) in Philadelphia chromosome—positive chronic myelogenous leukemia prior to the onset of blast crisis
Authors: Thomas Coyle, Vesna Najfeld
Journal: American Journal of Hematology (1988)

Abstract Two female patients in the chronic phase of CML were found to have, in addition to t(9;22), a new karyotypic abnormality—t(3;21)(q26;q22)—present in bone marrow cells. At diagnosis, this abnormality was observed in a small number of marrow cells in both patients, and as the disease progressed in patient 1, the percentage of cells showing t(3;21) was increased, reaching 100% as the transformation to blast crisis occurred. These observations suggest that t(3;21) may represent a new and rare nonrandom rearrangement which may be identified prior to the onset of blast crisis.
Prevalence and diagnosis of congenital uterine anomalies in women with reproductive failure: a critical appraisal
Authors: S. H. Saravelos, K. A. Cocksedge, T.-C. Li
Journal: Human Reproduction Update (2008)

BACKGROUNDThe prevalence of congenital uterine anomalies in women with reproductive failure remains unclear, largely due to methodological bias. The aim of this review is to assess the diagnostic accuracy of different methodologies and estimate the prevalence of congenital uterine anomalies in women with infertility and recurrent miscarriage (RM).
Expression of DNA Methyltransferase 1 Is Activated by Hepatitis B Virus X Protein via a Regulatory Circuit Involving the p16INK4a-Cyclin D1-CDK 4/6-pRb-E2F1 Pathway
Authors: Jin Kyu Jung, Payal Arora, Joseph S. Pagano, Kyung Lib Jang
Journal: Cancer Research (2007)

Abstract DNA methyltransferase 1 (DNMT1) is responsible for copying DNA methylation patterns to the daughter strands during DNA replication. Its expression is frequently up-regulated in human tumors, including hepatocellular carcinoma, but the mechanism of overexpression and its biological significance remain unclear. Here, we show that hepatitis B virus X protein (HBx) activates DNMT1 expression via a regulatory circuit involving the p16INK4a-cyclin D1-cyclin-dependent kinase (CDK) 4/6-retinoblastoma protein (pRb)-E2F1 pathway. HBx induced DNA hypermethylation of p16INK4a promoter to repress its expression, which subsequently led to activation of G1-CDKs, phosphorylation of pRb, activation of E2F1, and finally transcriptional activation of DNMT1. Inhibition of DNMT1 activity by either treatment with 5′-Aza-2′dC or introduction of DNMT1 small interfering RNA not only abolished the DNA methylation-mediated p16INK4a repression but also impaired DNMT1 expression itself, suggesting a cross-talk between DNMT1 and p16INK4a. The up-regulation of cyclin D1 by HBx is likely to serve as an initiative impulse for the circuit because it was absolutely required for the activation of DNMT1 expression. We also observed that accumulated DNMT1 via this pathway inactivates E-cadherin expression through promoter hypermethylation. Considering that the pRb-E2F1 pathway is commonly activated in human tumors, activation of this circuit might be widespread and a potential therapeutic target. [Cancer Res 2007;67(12):5771–8]
Natural human knockouts and the era of genotype to phenotype
Authors: Fowzan S Alkuraya
Journal: Genome Medicine (2015)

Complete loss of gene function in humans by naturally occurring biallelic loss-of-function mutations (human knockout) is not a new concept. However, the recent identification of human knockouts along the entire spectrum of health and disease by next-generation sequencing promises to unlock their full potential to accelerate the medical and functional annotation of the human genome.
Dozens of Toxin-Related Genes Are Expressed in a Nontoxic Strain of the Dinoflagellate Heterocapsa circularisquama
Authors: Tovah Salcedo, Ravi J. Upadhyay, Keizo Nagasaki, Debashish Bhattacharya
Journal: Molecular Biology and Evolution (2012)

The dinoflagellate Heterocapsa circularisquama is lethal to a variety of marine organisms, in particular, commercially important farmed bivalves. Unlike most dinoflagellate toxins, which are polyketides, the only described toxin from H. circularisquama (H2-a) is a porphyrin derivative that functions in light. It is unknown whether H2-a is produced specifically for its lytic properties. We searched for toxin-related genes in the transcriptome of a nontoxic strain of H. circularisquama, and surprisingly found the richest set of toxin-related genes yet described in dinoflagellates. There are 87 distinct expressed sequence tag contigs that encode polyketide synthases and nonribosomal peptide synthases, as well as 8 contigs that are involved in porphyrin biosynthesis. Phylogenomic analysis shows that many toxin-related genes are widely distributed among dinoflagellates. Our data likely indicate a variety of unknown metabolic functions for the toxin-related genes in H. circularisquama because they were identified in a nontoxic strain raised in unialgal culture.
The Role of Arachidonic Acid Oxygenation Products in Pain and Inflammation
Authors: Philip Davies, Philip J. Bailey, Marvin M. Goldenberg, Anthony W. Ford-Hutchinson
Journal: Annual Review of Immunology (1984)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Short chain fatty acids in human large intestine, portal, hepatic and venous blood.
Authors: J H Cummings, E W Pomare, W J Branch, C P Naylor, G T Macfarlane
Journal: Gut (1987)

Evidence for the occurrence of microbial breakdown of carbohydrate in the human colon has been sought by measuring short chain fatty acid (SCFA) concentrations in the contents of all regions of the large intestine and in portal, hepatic and peripheral venous blood obtained at autopsy of sudden death victims within four hours of death. Total SCFA concentration (mmol/kg) was low in the terminal ileum at 13 +/- 6 but high in all regions of the colon ranging from 131 +/- 9 in the caecum to 80 +/- 11 in the descending colon. The presence of branched chain fatty acids was also noted. A significant trend from high to low concentrations was found on passing distally from caecum to descending colon. pH also changed with region from 5.6 +/- 0.2 in the caecum to 6.6 +/- 0.1 in the descending colon. pH and SCFA concentrations were inversely related. Total SCFA (mumol/l) in blood was, portal 375 +/- 70, hepatic 148 +/- 42 and peripheral 79 +/- 22. In all samples acetate was the principal anion but molar ratios of the three principal SCFA changed on going from colonic contents to portal blood to hepatic vein indicating greater uptake of butyrate by the colonic epithelium and propionate by the liver. These data indicate that substantial carbohydrate, and possibly protein, fermentation is occurring in the human large intestine, principally in the caecum and ascending colon and that the large bowel may have a greater role to play in digestion than has previously been ascribed to it.
Heightened Expression of CTCF in Breast Cancer Cells Is Associated with Resistance to Apoptosis
Authors: France Docquier, Dawn Farrar, Vivien D'Arcy, Igor Chernukhin, Abigail F. Robinson, Dmitry Loukinov, Sergei Vatolin, Svetlana Pack, Alan Mackay, Robert A. Harris, Heather Dorricott, Michael J. O'Hare, Victor Lobanenkov, Elena Klenova
Journal: Cancer Research (2005)

CTCF is a candidate tumor suppressor gene encoding a multifunctional transcription factor. Surprisingly for a tumor suppressor, the levels of CTCF in breast cancer cell lines and tumors were found elevated compared with breast cell lines with finite life span and normal breast tissues. In this study, we aimed to investigate the possible cause for this increase in CTCF content and in particular to test the hypothesis that up-regulation of CTCF may be linked to resistance of breast cancer cells to apoptosis. For this purpose, apoptotic cell death was monitored following alterations of CTCF levels induced by transient transfection and conditional knockdown of CTCF in various cell lines. We observed apoptotic cell death in all breast cancer cell lines examined following CTCF down-regulation. In addition, overexpression of CTCF partially protected cells from apoptosis induced by overexpression of Bax or treatment with sodium butyrate. To elucidate possible mechanisms of this phenomenon, we used a proteomics approach and observed that levels of the proapoptotic protein, Bax, were increased following CTCF down-regulation in MCF7 cells. Taken together, these results suggest that in some cellular contexts CTCF shows antiapoptotic characteristics, most likely exerting its functions through regulation of apoptotic genes. We hypothesize that CTCF overexpression may have evolved as a compensatory mechanism to protect breast cancer cells from apoptosis, thus providing selective survival advantages to these cells. The observations reported in this study may lead to development of therapies based on selective reduction of CTCF in breast cancer cells.
Reexamination of the Applicability of the HIII Model of Muscle to Cat Myocardium
Authors: Mark I. M. Noble, Wendy Else
Journal: Circulation Research (1972)

In cat papillary muscles, which were perfused with oxygenated physiologic saline at 26°C and contracting isometrically at 15 beats/min, shortening steps were imposed 330 msec after stimulation-near the peak of isometric twitch force-and 170 msec or 250 msec after stimulation-during force development. The force immediately following the shortening step was measured. From the results at 330 msec, we predicted the results at the earlier times assuming that the sudden drop in force was due to recoil of a series elastic component (SEC) alone; however, the actual results differed from the predicted results. The shortening step required to drop the force to zero at the earlier times was greater than was predicted; in other words, the force immediately following a shortening step predicted to drop the force to zero was finite. The results are not compatible with the hypothesis that the sudden drop in force accompanying the shortening step (the quick-release phenomenon) is due to the sudden recoil of the SEC, which is stretched to different lengths at the two times. They are compatible with the hypotheses that (1) the quick-release phenomenon is a property of the contractile component or (2) the SEC compliance is a function of the degree of activation. Therefore, we concluded that nonseries elasticity contributes to the quick-release phenomenon and should be considered when the Hill model is applied to heart muscle. In particular, isometric contraction cannot be modeled by a contractile component stretching an SEC of constant physical characteristics.
Erythropoietin in polycystic kidneys.
Authors: K U Eckardt, M Möllmann, R Neumann, R Brunkhorst, H U Burger, G Lonnemann, H Scholz, G Keusch, B Buchholz, U Frei
Journal: Journal of Clinical Investigation (1989)

Erythropoietin (EPO) formation in kidneys of 18 patients with autosomal dominant polycystic kidney disease (ADPKD) was investigated. In 12 patients on hemodialysis and in 6 patients with preterminal renal failure serum, EPO was 29 +/- 7 and 16 +/- 1.5 mU/ml and hemoglobin concentrations were 11.0 +/- 0.6 and 12.7 +/- 1.2 g/dl, respectively. Cyst fluid from a total of 357 renal cysts was obtained by either in vivo aspiration or immediately after nephrectomy. The cysts contained variable concentrations of bioactive EPO from undectable values up to 3.2 U/ml. A pronounced enrichment of EPO was observed in cysts with sodium concentrations greater than 100 mmol/liter, suggesting an association with proximal tubular malformations. The EPO concentrations in the cysts were neither correlated with the protein concentration nor with the oxygen pressure of the cyst fluid. Using a cDNA probe for human EPO, mRNA for EPO was localized in stroma cells of the cyst walls by an in situ hybridization technique. Our findings suggest that single interstitial cells juxtaposed to proximal tubular cysts may produce EPO independent of the oxygen pressure inside the cysts, which ameliorates the anemia during end-stage polycystic kidney disease.
Fetoscopic laser coagulation of the vascular equator versus selective coagulation for twin-to-twin transfusion syndrome: an open-label randomised controlled trial
Authors: Femke Slaghekke, Enrico Lopriore, Liesbeth Lewi, Johanna M Middeldorp, Erik W van Zwet, Anne-Sophie Weingertner, Frans J Klumper, Philip DeKoninck, Roland Devlieger, Mark D Kilby, Maria Angela Rustico, Jan Deprest, Romain Favre, Dick Oepkes
Journal: The Lancet (2014)
New Figures on Global Dementia Cases
Authors: M. J. Friedrich
Journal: JAMA (2015)

Almost 47 million people around the world have some form of dementia, a number that is projected to double every 20 years, according to the "World Alzheimer Report 2015, The Global Impact of Dementia: An Analysis of Prevalence, Incidence, Cost, and Trends" (http://bit.ly/1LxgPfL).
Guidelines for Long-Term Steroid Therapy in End-of-Life Palliative Care
Authors: Hiromichi Yamane, Nobuaki Ochi, Tomoko Yamagishi, Nagio Takigawa
Journal: Journal of Clinical Oncology (2014)

Indicationsofshort-termsteroid therapy in oncological emergencies include bowel obstruc-tions, spinal cord compression, and superior vena cava syndrome. Inaddition, steroids can be useful for the treatment of nausea, dyspnea,anorexia, weight loss, fatigue, and in improving a patient’s generalfeeling of well-being. However, steroids have a limited effect (lastingfor up to 4 weeks) on these symptoms.
Hydatidiform mole and triploidy: the role of genomic imprinting in placental development
Authors: Koen Devriendt
Journal: Human Reproduction Update (2005)

Genomic imprinting, the differential expression of paternal and maternal alleles, is involved in the regulation of embryonic and fetal growth and development. In this review, we focus on the genetics of a disorder caused by a global defect in genomic imprinting, the hydatidiform mole. The ratio between the maternal and paternal genomes is critical in determining the development of both the embryonic and extraembryonic tissues, with an excess of paternally derived chromosomes leading to a complete (no maternal genome) or partial (lower amount of maternal chromosomes) mole. The recent identification and molecular studies in biparental complete moles may yield more insight into the regulation of imprinting during gametogenesis.
Rewiring of hindlimb corticospinal neurons after spinal cord injury
Authors: Arko Ghosh, Florent Haiss, Esther Sydekum, Regula Schneider, Miriam Gullo, Matthias T Wyss, Thomas Mueggler, Christof Baltes, Markus Rudin, Bruno Weber, Martin E Schwab
Journal: Nature Neuroscience (2009)
Myocardial Gd-DTPA Kinetics Determine MRI Contrast Enhancement and Reflect the Extent and Severity of Myocardial Injury After Acute Reperfused Infarction
Authors: Raymond J. Kim, Enn-Ling Chen, Joa˜o A.C. Lima, Robert M. Judd
Journal: Circulation (1996)

Background Contrast medium–enhanced magnetic resonance images of acute, reperfused infarcts have shown hypoenhanced and hyperenhanced regions in areas of injured myocardium. The precise mechanisms that lead to these altered enhancement patterns are unknown. This study was designed to evaluate possible mechanisms and to relate altered enhancement patterns to myocardial perfusion and viability. Methods and Results Thirteen rabbits underwent in situ coronary artery occlusion and reperfusion followed by isolated perfusion with cardioplegic solution. T1-weighted spin-echo images were acquired continuously during step changes in perfusate Gd-DTPA concentration. Regional blood flow was also measured by use of radioactive microspheres in all rabbits. There were marked differences in Gd-DTPA wash-in and washout time constants (wash-in, 0.8±0.1, 2.1±0.2, and 16.3±2.4 minutes, P &lt;.001; washout, 1.6±0.1, 4.8±0.5, and 31.1±3.3 minutes, P &lt;.001) in normal, infarct rim, and infarct core regions, respectively, resulting in differential enhancement of these regions. Microsphere flows in the infarct rim and core were 42.9±4.0% and 12.0±1.6% of normal myocardium and correlated well with washout time constants ( r =.86, y =0.77 x −0.002, P &lt;.001), suggesting that these time constants index the severity of microvascular damage. In addition, spatial maps of washout time constants were produced. The extent of regions with abnormal time constants correlated well with triphenyltetrazolium chloride–determined infarct size ( r =.94, y =0.95 x +4.17, P &lt;.001). Conclusions In contrast-enhanced magnetic resonance images of acute, reperfused rabbit infarcts, differential image intensity is primarily due to regional differences in contrast agent wash-in and washout time constants. These regional differences in time constants also indicate the extent and severity of myocardial injury.
Imbalance between vascular endothelial growth factor and endostatin in emphysema
Authors: H. Kanazawa, K. Hirata, J. Yoshikawa
Journal: European Respiratory Journal (2003)

Vascular endothelial growth factor (VEGF) stimulates endothelial cell proliferation, and endostatin directly antagonises the biological effects of VEGF. The maintenance of pulmonary endothelial cells is also thought to depend upon the local balance of VEGF and endostatin in the lung. Therefore, this study was designed to determine whether there is an imbalance between VEGF and endostatin levels in patients with pulmonary emphysema. VEGF and endostatin levels were simultaneously measured from 25 emphysema patients and 12 normal control subjects, and their correlation and balance in induced sputum was evaluated. VEGF levels in induced sputum were significantly lower in emphysema patients (854±307 pg·mL −1 ) than in normal controls (1,791±1,192 pg·mL −1 ). In contrast, there was no significant difference in endostatin levels among the two groups. Therefore, the ratio of VEGF to endostatin levels was markedly lower in emphysema patients (4.5±1.8) than in normal controls (8.1±2.6). Moreover, VEGF levels were correlated with endostatin levels in normal controls but not in emphysema patients. In addition, the ratio of VEGF to endostatin levels was correlated with forced expiratory volume in one second (FEV 1 ), FEV 1 /forced vital capacity and carbon monoxide diffusing capacity of the lung in emphysema patients. The findings in this study suggest that there is an imbalance between vascular endothelial growth factor and endostatin levels in induced sputum from emphysema patients.
Association between Kinin B1 Receptor Expression and Leukocyte Trafficking across Mouse Mesenteric Postcapillary Venules
Authors: Peter G. McLean, Amrita Ahluwalia, Mauro Perretti
Journal: The Journal of Experimental Medicine (2000)

Using intravital microscopy, we examined the role played by B(1) receptors in leukocyte trafficking across mouse mesenteric postcapillary venules in vivo. B(1) receptor blockade attenuated interleukin (IL)-1beta-induced (5 ng intraperitoneally, 2 h) leukocyte-endothelial cell interactions and leukocyte emigration ( approximately 50% reduction). The B(1) receptor agonist des-Arg(9)bradykinin (DABK), although inactive in saline- or IL-8-treated mice, caused marked neutrophil rolling, adhesion, and emigration 24 h after challenge with IL-1beta (when the cellular response to IL-1beta had subsided). Reverse transcriptase polymerase chain reaction and Western blot revealed a temporal association between the DABK-induced response and upregulation of mesenteric B(1) receptor mRNA and de novo protein expression after IL-1beta treatment. DABK-induced leukocyte trafficking was antagonized by the B(1) receptor antagonist des-arg(10)HOE 140 but not by the B(2) receptor antagonist HOE 140. Similarly, DABK effects were maintained in B(2) receptor knockout mice. The DABK-induced responses involved the release of neuropeptides from C fibers, as capsaicin treatment inhibited the responses. Treatment with the neurokinin (NK)(1) and NK(3) receptor antagonists attenuated the responses, whereas NK(2), calcitonin gene-related peptide, or platelet-activating factor receptor antagonists had no effect. Substance P caused leukocyte recruitment that, similar to DABK, was inhibited by NK(1) and NK(3) receptor blockade. Mast cell depletion using compound 48/80 reduced DABK-induced leukocyte trafficking, and DABK treatment was shown histologically to induce mast cell degranulation. DABK-induced trafficking was inhibited by histamine H(1) receptor blockade. Our findings provide clear evidence that B(1) receptors play an important role in the mediation of leukocyte-endothelial cell interactions in postcapillary venules, leading to leukocyte recruitment during an inflammatory response. This involves activation of C fibers and mast cells, release of substance P and histamine, and stimulation of NK(1), NK(3), and H(1) receptors.
Introducing a Series of Notable Notes About Historical Figures
Authors: June K. Robinson
Journal: JAMA Dermatology (2013)

As the oldest English-language dermatology journal in continuous publication, it is appropriate for JAMA Dermatology to acknowledge the English-language publication of a landmark text of dermatologic medical history: Pantheon of Dermatology: Outstanding Historical Figures by Christoph Loser, Gerd Plewig, and Walter Burgdorf, published by Springer in 2013. The text and over 2200 illustrations provide insight into the lives of 209 outstanding dermatologists who developed dermatology over 6 centuries. Since the founding of JAMA Dermatology in 1882 as the Journal of Cutaneous and Venereal Disease, the journal has published definitive manuscripts by the leaders in our field. It is a privilege to be able to give a glimpse into the lives of some of these leaders with Notable Notes derived from the Pantheon of Dermatology.
Intraventricular reentry with narrow QRS complex.
Authors: C P Reddy, A Khorasanchian
Journal: Circulation (1980)

Reentry within the His-Purkinje System (V3 phenomenon) where the reentry pathway incorporates both bundle branches and the bundle of His is a frequent phenomenon during ventricular refractory period studies. In this form of reentry, both divisions of the left bundle branch function as a single limb and the reentrant beats (V3) have either left bundle branch block or right bundle branch block pattern. In this report, we describe in three patients the occurrence of a new type of reentrant beat (V3) whose characteristics suggested reentry within a circuit in which the retrograde limb of the reentrant circuit was constituted by one of the two divisions of the left bundle branch and the antegrade limb(s) by right bundle branch and the remaining division of the left bundle branch; i.e., the two divisions of the left bundle branch functioned as two separate limbs. We reached this conclusion because 1) reentry occurred within a narrow range of V1V2 intervals and was dependent upon critical retrograde His-Purkinje conduction (V2H2) delays; 2) reentry did not occur when the V2 impulse blocked retrogradely within the His-Purkinje system below the site of His bundle recording; 3) the QRS duration of V3 was less than 90 msec; and 4) in two-thirds of the patients, the HV interval of V3 was the same as that of sinus beats.
Implications of inhomogeneous distribution of IKS and IKr channels in ventricle with respect to effects of class III agents and beta-agonists
Authors: A van Ginneken
Journal: Cardiovascular Research (1999)

See article byCheng et al. ([1], pages 135 -147) in this myocytes I is the largest component.These findings Ks issue.show that I and I are regionally different distributed.Kr Ks Indications of regional variation in I characteristics were K In this issue of Cardiovascular Research Cheng et al. [1] found earlier as transmural differences in feline and canine demonstrate that the electrical properties of single cells ventricle [9,10].Brahmajothi et al. [18] showed that isolated from apex and base are different.They show that HERG, which forms the channel for I , is more abun-Kr