tbuckley/cabot-search huggingface dataset:
Author's reply to “rearrangement of the BCR/ABL and TCR‐β genes in lymph node blast crisis diagnosed of chronic myeloid leukemia”
Authors: R. van der Jagt, J. Drouin, A. Giulivi, L. B. Huebsch, P. Tittley
Journal: American Journal of Hematology (1994)

To rhe Editor: Drs.Villegas and Gonzalez suggest that, on the basis of their experience with one case of lymphoid blast crisis, presenting with lymphadenopathy, the BCRIABL gene rearrangements detected in the lymph node should be consistent with those found in the peripheral blood or bone marrow.In our case 111, we reported that the rearrangements seen with a BamHI digestion were seen only in the lymph node samples but not in the peripheral blood cells, whereas rearrangements were seen in lymph node and peripheral blood with both BglII and EcoRI enzymes.As a result of Drs.Villegas and Gonzlles letter, we asked for a review of the blots of our case by an independent reviewer.The resuits were confirmed as we had reported.Unfottunately , repeat studies were not possible, because the patient died rapidly before further specimens could be taken.As was mentioned in our letter, cytogenetics and morphology of marrow and peripheral blood taken at the time of diagnosis of the lymphoma were consistent with chronic-phase CML.As was reported in our letter, our case of T-cell lymphoma might in fact have been a form of CML blast crisis.However, we could not exclude the possibility that the T-cell lymphoma and CML arose separately from a common ancestral clone.Our single case report was meant only to raise the possibility of the two models, and we prefer to await confirmation of this finding in other cases in the future.
Functional and Structural Correlates of Glomerulosclerosis after Renal Mass Reduction in the Rat
Authors: KAREN A. GRIFFIN, MARIA M. PICKEN, MONIQUE CHURCHILL, PAUL CHURCHILL, ANIL K. BIDANI
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Previously, it was shown that 5/6 renal mass reduction by surgical excision (RK-NX) results in a marked reduction of glomerulosclerosis (GS) at 6 wk compared with the conventional 5/6 renal ablation by infarction (RK-I) model. To determine the pathogenetic correlates of the striking differences in GS, radiotelemetrically measured BP; single nephron function; glomerular volume; the temporal expression of mRNA for renin, transforming growth factor-β, and platelet-derived growth factor-B; and plasma renin concentration were compared between RK-NX, RK-I, and sham-operated control rats. Hypertension only developed in the RK-I model, was present at 3 d after infarction, and was correlated with both an increased expression of renin mRNA by Northern analysis and elevated plasma renin concentration. Structural (glomerular volume) and functional (single nephron blood flow and GFR) indices of the compensatory adaptive response were significantly but similarly increased in the RK-NX and RK-I rats compared with sham-operated controls, indicating that these adaptations per se are not responsible for the initiation of GS after 5/6 renal mass reduction. Glomerular capillary pressure ( P GC ) was also significantly increased in both RK-I (56 ± 2 mmHg) and RK-NX rats (50 ± 0.9 mmHg) compared with controls (46 ± 0.8 mmHg, P &lt; 0.01), but the increase was significantly greater in RK-I versus RK-NX rats ( P &lt; 0.05) consistent with the higher BP in RK-I rats. These data indicate that differences in renin probably account for the early divergence of BP (and P GC ) responses between RK-I and RK-NX models. Transforming growth factor-β and platelet-derived growth factor-B mRNA expression in pooled RNA from kidneys from each group showed increases at 21 d along with early evidence of glomerular injury in the RK-I group but not in the RK-NX group, consistent with their postulated roles as molecular mediators of GS, but only in rats with pathologic glomerular hypertension.
Excellent survival after sibling or unrelated donor stem cell transplantation for chronic granulomatous disease
Authors: Caridad A. Martinez, Sweta Shah, William T. Shearer, Howard M. Rosenblatt, Mary E. Paul, Javier Chinen, Kathryn S. Leung, Alana Kennedy-Nasser, Malcolm K. Brenner, Helen E. Heslop, Hao Liu, Meng-Fen Wu, Imelda C. Hanson, Robert A. Krance
Journal: Journal of Allergy and Clinical Immunology (2011)
At return to play following hamstring injury the majority of professional football players have residual isokinetic deficits
Authors: Johannes L Tol, Bruce Hamilton, Cristiano Eirale, Patrice Muxart, Philipp Jacobsen, Rod Whiteley
Journal: British Journal of Sports Medicine (2014)

Background There is an ongoing debate regarding the optimal criteria for return to sport after an acute hamstring injury. Less than 10% isokinetic strength deficit is generally recommended but this has never been documented in professional football players after rehabilitation. Our aim was to evaluate isokinetic measurements in MRI-positive hamstring injuries. Methods Isokinetic measurements of professional football players were obtained after completing a standardised rehabilitation programme. An isokinetic strength deficit of more than 10% compared with the contralateral site was considered abnormal. Reinjuries within 2 months were recorded. Results 52 players had a complete set of isokinetic testing before clinical discharge. There were 27 (52%) grade 1 and 25 (48%) grade 2 injuries. 35 of 52 players (67%) had at least one of the three hamstring-related isokinetic parameters that display a deficit of more than 10%. The percentage of players with 10% deficit for hamstring concentric 60°/s, 300°/s and hamstring eccentric was respectively 39%, 29% and 28%. There was no significant difference of mean isokinetic peak torques and 10% isokinetic deficits in players without reinjury (N=46) compared with players with reinjury (N=6). Conclusions When compared with the uninjured leg, 67% of the clinically recovered hamstring injuries showed at least one hamstring isokinetic testing deficit of more than 10%. Normalisation of isokinetic strength seems not to be a necessary result of the successful completion of a football-specific rehabilitation programme. The possible association between isokinetic strength deficit and increased reinjury risk remains unknown.
Evolution of tuberculosis in an area of Vizcaya
Authors: Sandra Pedrero Tejada, Begoña Vilar Achabal, Maria Alfonso Imizcoz, Israel Lopez Mirones, Luis Miguel Soria Riendas, Nuria Marina Malanda, Ines Martinez Rienda, Esteban Ciruelos Ayuso, Rafael Zalacain Jorge, Elena Urra Zalbidegoitia
Journal: European Respiratory Journal (2011)

Aim:  To study the evolution of Mycobacterium tuberculosis (MT) over a period of 21 years in our area and to know the resistance rates to first-line antituberculostatic drugs.   Material and methods:  We studied all cases of MT infection diagnosed between 1989 and 2009 in our hospital, attending a population of 420.000.   Results:  In this period, 2.164 cases of MT infection have been diagnosed. The mean incidence rate was 24.5 per 100,000 inhabitants per year (maximum 42.6 in 1992 and minimum 11.9 in 2008). The mean age was 46.8, with a higher incidence in the group of 30-49 years.The gender distribution was 1.8 men/women. In 262 cases there was coinfection with HIV (12.1%), with a maximum of 23.6% (n = 35) in 1993 and minimum of 2.5% (n = 2) in 2004.  The location was pulmonary in 74.2%, extrapulmonary in 20.1% and disseminated in 5.7%. In patients co-infected with HIV, the presentation was pulmonary in 61.4%, extrapulmonary in 13.4% and disseminated in 25.2%. 61 strains have been detected with some resistance (2.8% of general population, which corresponds to 3% in non-HIV and 1.5% of coinfected). There were 36 strains resistant to isoniazid (1.7%), 11 to rifampicin (0.5%), 3 to ethambutol (0.14%) and 25 to streptomycin (1.2%). 17 strains were resistant to more than one drug. Of these, 6 were resistant to at least isoniazid and rifampicin (MDR-TB).   Conclusions:  1.The incidence of MT has clearly diminished over the study period. 2. There has been no change over the years in terms of gender distribution, age groups and location of MT. 3. HIV co-infection has less importance as a risk factor associated. 4. Resistance to first-line drugs is rare in our area and maintains stable levels. 5. We have found some MDR-TB in the study period.
Circulating Matrix Metalloproteinases and Their Inhibitors in Patients with Kawasaki Disease
Authors: Hideaki Senzaki, Satoshi Masutani, Jun Kobayashi, Toshiki Kobayashi, Hirofumi Nakano, Hironori Nagasaka, Nozomu Sasaki, Haruhiko Asano, Shunei Kyo, Yuji Yokote
Journal: Circulation (2001)

Accelerated matrix breakdown caused by the increased activity of matrix metalloproteinases (MMPs) and/or the quantitative imbalance between MMP and tissue inhibitor of MMP (TIMP) have been implicated in several pathological conditions. MMP and TIMP may also be involved in the destruction of the coronary arterial wall and the resultant coronary arterial lesions in Kawasaki disease.Plasma levels of MMPs, neutrophil elastase, and TIMPs were measured by enzyme-linked immunoassay in 57 patients with Kawasaki disease and no coronary arterial lesions (group 1) and in 8 patients with Kawasaki disease and coronary arterial lesions (group 2). Blood samples were obtained before and after intravenous gamma globulin therapy and in the convalescent stage. Levels of MMPs, neutrophil elastase, and TIMPs were significantly higher in Kawasaki disease patients before gamma globulin therapy than in 18 age-matched afebrile control subjects and 17 age-matched febrile disease control subjects (P<0.01). More importantly, the pre-gamma globulin MMP9 level and MMP9/TIMP2 ratio and post-gamma globulin MMP3 level and MMP3/TIMP1 ratio were significantly higher in group 2 than in group 1 patients (P<0.05). Although MMP levels in febrile disease controls were significantly higher than those of afebrile controls, the MMP/TIMP ratios of febrile disease controls and afebrile controls were comparable.These data suggest that patients with Kawasaki disease and high levels of MMP and/or MMP/TIMP are susceptible to coronary arterial lesions. Studies of the effects of MMP inhibitors on coronary outcome may provide evidence that MMP is a viable therapeutic target for the prevention of coronary arterial lesions due to Kawasaki disease.
Secondary Structure in Denatured DNA is Responsible for Its Reaction with Antinative DNA Antibodies of Systemic Lupus Erythematosus Sera
Authors: B. David Stollar, Michael Papalian
Journal: Journal of Clinical Investigation (1980)

Experiments were designed to determine the basis for the strong competitive reaction of denatured DNA with systemic lupus erythematosus (SLE) antinative DNA antibodies. Secondary structure in denatured DNA was reflected in hyperchromicity upon heating and in multiphase kinetics of its digestion by S1 nuclease. Partial digestion by S1 nuclease completely eliminated the ability of denatured DNA to react with antidenatured DNA antibodies, but not its ability to react with SLE sera. S1 nuclease-resistant cores were isolated from extensively digested denatured DNA. These cores had secondary structure, including some stable fold-back helical regions. The cores, from 20 to several hundred base pairs in size, competed with native DNA for binding by SLE sera. Other experiments measured reactions of denatured DNA under conditions that affected its secondary structure content. Its competitive activity decreased as temperature was increased from 0° to 37°C, whereas the activity of native DNA was not altered in this temperature range. With DNA pieces of 90-110 base pairs, native fragments were much more effective than the denatured fragments, in which stable helical structure is less likely to occur than in high molecular weight denatured DNA. Competitive assays with mononucleotides, oligonucleotides, homopolymers, and RNA-DNA hybrids also indicated that two strands of polydeoxyribonucleotide were required for optimal reactions with these SLE serum antibodies. The antibodies can measure stable helical regions in denatured DNA; they may also stabilize short helical regions that occur in an equilibrium of conformational forms.
Adenosine-Sensitive Ventricular Tachycardia
Authors: Steven M. Markowitz, Bonnie L. Litvak, Elizabeth A. Ramirez de Arellano, John A. Markisz, Kenneth M. Stein, Bruce B. Lerman
Journal: Circulation (1997)

Background Adenosine-sensitive ventricular tachycardia (VT) is thought to be due to cAMP-mediated triggered activity. It typically originates from the RVOT and occurs in patients with apparently normal hearts. Using magnetic resonance imaging (MRI), we tested the hypothesis that adenosine-sensitive VT occurs in patients without structural heart disease. Methods and Results Fourteen patients (9 women; age, 47±19 years) presented with sustained VT (n=3), repetitive monomorphic VT (n=7), or both (n=4). VT terminated with adenosine in each patient and was sensitive to vagal maneuvers in 9 of 11 and verapamil in 10 of 12. VT originated from the right ventricular outflow tract in 10 patients, the right ventricular apex in 1, and the left ventricular septum in 3. Conventional studies included normal signal-averaged ECGs in 9 of 9, normal right ventricular echocardiography in 10 of 10, and normal left ventriculography and coronary angiography in 6 of 7. In contrast, MRI scans were abnormal in 10 of 14 patients. These abnormalities included focal thinning (6), fatty infiltration (4), and wall motion abnormalities (4) of the right ventricle. The most common site of MRI abnormalities was the right ventricular free wall, but there was a poor correlation between the site of MRI abnormalities and the origin of VT. Among 18 control patients without clinical heart disease, thinning of the right ventricular wall was noted in only 1 patient (patients versus control subjects, P =.0001). Conclusions Patients with idiopathic adenosine-sensitive VT comprise a heterogeneous group as assessed by MRI, with 70% demonstrating mild structural abnormalities. However, it is unlikely that these findings are causally related to tachycardia, and the functional significance of these anatomic abnormalities is uncertain.
Relaxation of tracheal smooth muscle is impaired in innate airway hyperresponsiveness
Authors: F-X. Blanc, C. Coirault, P. Oliviero, Y. Lecarpentier
Journal: European Respiratory Journal (2009)

The current study was designed to determine whether the nonspecific in vivo airway hyperresponsiveness of the inbred Fisher F-344 rat strain is associated with impaired spontaneous relaxation of airway smooth muscle. Strips of the posterior portion of the trachea from 10 adult Fisher and 10 adult Lewis rats were electrically stimulated at pH 7.4, 2.5 mM Ca 2+ concentration, at 37°C. Both isotonic and isometric relaxations of tracheal smooth muscle (TSM) were investigated. Half time for isotonic relaxation at preload was markedly prolonged in Fisher rats (8.33±3.21 s) compared with Lewis rats (3.53±0.54 s; p&lt;0.001). Maximum lengthening velocity at preload and peak rate of isometric tension decline were significantly decreased in Fisher rats compared with Lewis rats. The ratio of shortening velocity to lengthening velocity at preload, as well as the ratio of the isometric peak rates of tension development to tension decline were higher in Fisher rat TSM than in Lewis rat TSM. These differences were associated with a six-fold higher expression of myosin light chain kinase in Fisher rats than in Lewis rats. In Fisher rats, these results suggest that innate airway hyperresponsiveness is associated with both a reduced level and a slower rate of TSM spontaneous relaxation, promoting maintenance of airway constriction.
Global analysis of patterns of gene expression during Drosophila embryogenesis
Authors: Pavel Tomancak, Benjamin P Berman, Amy Beaton, Richard Weiszmann, Elaine Kwan, Volker Hartenstein, Susan E Celniker, Gerald M Rubin
Journal: Genome biology (2007)

Abstract Background Cell and tissue specific gene expression is a defining feature of embryonic development in multi-cellular organisms. However, the range of gene expression patterns, the extent of the correlation of expression with function, and the classes of genes whose spatial expression are tightly regulated have been unclear due to the lack of an unbiased, genome-wide survey of gene expression patterns. Results We determined and documented embryonic expression patterns for 6,003 (44%) of the 13,659 protein-coding genes identified in the Drosophila melanogaster genome with over 70,000 images and controlled vocabulary annotations. Individual expression patterns are extraordinarily diverse, but by supplementing qualitative in situ hybridization data with quantitative microarray time-course data using a hybrid clustering strategy, we identify groups of genes with similar expression. Of 4,496 genes with detectable expression in the embryo, 2,549 (57%) fall into 10 clusters representing broad expression patterns. The remaining 1,947 (43%) genes fall into 29 clusters representing restricted expression, 20% patterned as early as blastoderm, with the majority restricted to differentiated cell types, such as epithelia, nervous system, or muscle. We investigate the relationship between expression clusters and known molecular and cellular-physiological functions. Conclusion Nearly 60% of the genes with detectable expression exhibit broad patterns reflecting quantitative rather than qualitative differences between tissues. The other 40% show tissue-restricted expression; the expression patterns of over 1,500 of these genes are documented here for the first time. Within each of these categories, we identified clusters of genes associated with particular cellular and developmental functions.
Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model
Authors: Lee E. Goldstein, Andrew M. Fisher, Chad A. Tagge, Xiao-Lei Zhang, Libor Velisek, John A. Sullivan, Chirag Upreti, Jonathan M. Kracht, Maria Ericsson, Mark W. Wojnarowicz, Cezar J. Goletiani, Giorgi M. Maglakelidze, Noel Casey, Juliet A. Moncaster, Olga Minaeva, Robert D. Moir, Christopher J. Nowinski, Robert A. Stern, Robert C. Cantu, James Geiling, Jan K. Blusztajn, Benjamin L. Wolozin, Tsuneya Ikezu, Thor D. Stein, Andrew E. Budson, Neil W. Kowall, David Chargin, Andre Sharon, Sudad Saman, Garth F. Hall, William C. Moss, Robin O. Cleveland, Rudolph E. Tanzi, Patric K. Stanton, Ann C. McKee
Journal: Science Translational Medicine (2012)

Blast exposure is associated with chronic traumatic encephalopathy, impaired neuronal function, and persistent cognitive deficits in blast-exposed military veterans and experimental animals.
Modification of Human Hearing Loss by Plasma-Membrane Calcium Pump PMCA2
Authors: Julie M. Schultz, Yandan Yang, Ariel J. Caride, Adelaida G. Filoteo, Alan R. Penheiter, Ayala Lagziel, Robert J. Morell, Saidi A. Mohiddin, Lameh Fananapazir, Anne C. Madeo, John T. Penniston, Andrew J. Griffith
Journal: New England Journal of Medicine (2005)

Five adult siblings presented with autosomal recessive sensorineural hearing loss: two had high-frequency loss, whereas the other three had severe-to-profound loss affecting all frequencies. Genetic evaluation revealed that a homozygous mutation in CDH23 (which encodes cadherin 23) caused the hearing loss in all five siblings and that a heterozygous, hypofunctional variant (V586M) in plasma-membrane calcium pump PMCA2, which is encoded by ATP2B2, was associated with increased loss in the three severely affected siblings. V586M was detected in two unrelated persons with increased sensorineural hearing loss, in the other caused by a mutation in MYO6 (which encodes myosin VI) in one and by noise exposure, suggesting that this variant may modify the severity of sensorineural hearing loss caused by a variety of factors.
Genetic ablation of solute carrier family 7a3a leads to hepatic steatosis in zebrafish during fasting
Authors: Qilin Gu, Xiaojie Yang, Li Lin, Shaoyang Li, Qing Li, Shan Zhong, Jinrong Peng, Zongbin Cui
Journal: Hepatology (2014)

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder caused by abnormal lipid metabolisms, such as reduced hepatic fatty acid oxidation (FAO), but intracellular control of FAO under physio- and pathological conditions remains largely undefined. Here, we demonstrate that deprivation of Slc7a3a leads to hepatic steatosis in fasted zebrafish as a result of defects in arginine-dependent nitric oxide (NO) synthesis. Fast-induced hepatic steatosis in slc7a3a-null mutants can be rescued by treatments with NO donor, cyclic guanosine monophosphate analog, adenosine-monophosphate-activated protein kinase (AMPK) activator, or peroxisome proliferator-activated receptor alpha (PPAR-α) agonist. In contrast, inhibitors of NO synthases, AMPK, or soluble guanylate cyclase and liver-specifically expressed dominant negatives of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha and PPAR-α are sufficient to induce hepatic steatosis in fasted wild-type larvae. Moreover, knockdown of Slc7a3 in mice or SLC7A3 in human liver cells impaired AMPK-PPAR-α signaling and resulted in lipid accumulation under fasting or glucose starvation, respectively.These findings have revealed a NO-AMPK-PPAR-α-signaling pathway that is crucial for the control of hepatic FAO in vertebrates.
Acquired delayed rectifier channelopathies: how heart disease and antiarrhythmic drugs mimic potentially-lethal congenital cardiac disorders
Authors: S Nattel
Journal: Cardiovascular Research (2000)

See article by Tsuji et al. [10] (pages 300–309) in this issue. 

The discovery of the molecular bases of the congenital long QT syndromes (LQTSs) [1–5] has created an explosion of insight, not only into these relatively rare congenital abnormalities, but also into the broader function of delayed rectifier channels in the heart. Recent reviews have covered the pathophysiology of these syndromes in detail [6,7] with arrhythmogenesis due to defects at the level of the density of repolarizing current and/or abnormal kinetics. The evolving knowledge has highlighted the role of the rapid component ( I Kr) of delayed rectifier current ( I K) as a primary repolarizing current in ventricular tissue (including the human heart) and of the slower component ( I Ks) as an important ‘safety factor’ in the presence of adrenergic stimulation [8] or prolonged action potentials (APs) [9].

The article by Tsuji et al. in the present issue [10] is part of a rapidly-evolving body of knowledge that points to acquired conditions that may predispose to potentially lethal ventricular tachyarrhythmias while recreating ionic abnormalities associated with congenital LQTSs. Tsuji et al. show that congestive heart failure (CHF) results in downregulation of a variety of ionic currents in ventricular myocytes, including L-type Ca2+ current ( I Ca), Ca2+-independent transient outward K+ current ( I to) and I K [10]. Decreased I to is well-known to occur in a range of cardiac conditions, including CHF [11], the post-myocardial infarction state [12], and tachycardia-induced atrial remodeling [13]. Reductions in I Ca have been reported to occur in CHF by some investigators [14] but not others [11,15]. Less has been known about changes in I K in cardiac disease states.

An important novel contribution of the Tsuji paper is the convincing demonstration that ventricular I K … 

* Tel.: +1-514-376-3330; fax: +1-514-593-2521 nattel{at}icm.umontreal.ca