tbuckley/cabot-search huggingface dataset:
ADSORPTION OF INFLUENZA HEMAGGLUTININS AND VIRUS BY RED BLOOD CELLS
Authors: G. K. Hirst
Journal: The Journal of Experimental Medicine (1942)

A number of experiments were performed on the adsorption of influenza hemagglutinins on chicken red blood cells, from which the following conclusions were drawn:- 1. When chicken red blood cells and preparations of influenza viruses were mixed together, the influenza hemagglutinins present were rapidly adsorbed onto the cells. After varying lengths of time, dependent on the conditions of the experiment, the adsorbed hemagglutinins began to elute from the cells. With the Lee strain at 23 degrees C. and the PR8 strain at 37 degrees C. almost all of the adsorbed agglutinin was released in 4 to 6 hours. 2. When the number of red cells used for adsorption was increased, the speed and degree of adsorption of the hemagglutinins increased. The time of maximum adsorption of hemagglutinins was the same, regardiess of red cell concentration, and with the larger amounts of red cells the speed and degree of elution was decreased. 3. When adsorption of PR8 virus agglutinins was carried out at 4 degrees C. the adsorption was rapid and nearly complete. When the reaction was carried out at higher temperatures (27 degrees and 37 degrees C.), the adsorption was equally rapid but was progressively less complete with rise in temperature. At 4 degrees C. the maximum adsorption was not reached for 5 hours; at 27 degrees C. it was reached in 25 minutes; and at 37 degrees C. the greatest degree of adsorption was attained between 3 and 5 minutes. The amount of elution observed at 4 degrees C. at 18 hours was negligible, but the degree of elution increased with temperature so that at 37 degrees C. almost all of the adsorbed agglutinin was released in 6 hours' time. 4. Red cells which had adsorbed and then fully eluted the agglutinin were not capable of adsorbing a detectable amount of fresh agglutinin. In addition, such cells would no longer agglutinate even though exposed to fresh virus suspensions. 5. The hemagglutinin of influenza B virus was capable of being adsorbed on and eluted from several successive lots of chicken red cells without appreciable loss of agglutinating activity. 6. The hemagglutinins of the PR8 and Lee strains were rapidly inactivated at 60 degrees C. The presence of active virus was not necessary for the occurrence of the adsorption-elution reaction on chicken red cells. 7. The activity of the portion of the red cells responsible for the adsorption of the hemagglutinins persisted, though in reduced amount, even after heating for 5 minutes at 100 degrees C. Hemagglutinins were adsorbed and eluted from red cell stroma. 8. The infective agent in influenza virus suspensions was adsorbed by chicken red cells simultaneously with the adsorption of hemagglutinins. 95 per cent of the infective agent was removed from suspension by the red cells after contact for 15 minutes. From then on the infective agent was gradually released from the red cells. After 4 hours the 50 per cent mortality titer of the supernatant fluid was as high as at the beginning of the experiment.
Pharmacological and Protein Profiling Suggests Venetoclax (ABT-199) as Optimal Partner with Ibrutinib in Chronic Lymphocytic Leukemia
Authors: Fabiola Cervantes-Gomez, Betty Lamothe, Jennifer A. Woyach, William G. Wierda, Michael J. Keating, Kumudha Balakrishnan, Varsha Gandhi
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Bruton's tyrosine kinase (BTK) is a critical enzyme in the B-cell receptor pathway and is inhibited by ibrutinib due to covalent binding to the kinase domain. Though ibrutinib results in impressive clinical activity in chronic lymphocytic leukemia (CLL), most patients achieve only partial remission due to residual disease. We performed a pharmacologic profiling of residual circulating CLL cells from patients receiving ibrutinib to identify optimal agents that could induce cell death of these lymphocytes. Experimental Design: Ex vivo serial samples of CLL cells from patients on ibrutinib were obtained prior and after (weeks 2, 4, and 12) the start of treatment. These cells were incubated with PI3K inhibitors (idelalisib or IPI-145), bendamustine, additional ibrutinib, or BCL-2 antagonists (ABT-737 or ABT-199), and cell death was measured. In vitro investigations complemented ex vivo studies. Immunoblots for BTK signaling pathway and antiapoptotic proteins were performed. Results: The BCL-2 antagonists, especially ABT-199, induced high cell death during ex vivo incubations. In concert with the ex vivo data, in vitro combinations also resulted in high cytotoxicity. Serial samples of CLL cells obtained before and 2, 4, 12, or 36 weeks after the start of ibrutinib showed inhibition of BTK activity and sensitivity to ABTs. Among the three BCL-2 family antiapoptotic proteins that are overexpressed in CLL, levels of MCL-1 and BCL-XL were decreased after ibrutinib while ABT-199 selectively antagonizes BCL-2. Conclusions: Our biologic and molecular results suggest that ibrutinib and ABT-199 combination should be tested clinically against CLL. Clin Cancer Res; 21(16); 3705–15. ©2015 AACR.
Desferrioxamine induces leukemic cell differentiation potentially by hypoxia-inducible factor-1α that augments transcriptional activity of CCAAT/enhancer-binding protein-α
Authors: Y Jiang, Z-H Xue, W-Z Shen, K-M Du, H Yan, Y Yu, Z-G Peng, M-G Song, J-H Tong, Z Chen, Y Huang, M Lübbert, G-Q Chen
Journal: Leukemia (2005)
Exertional dyspnoea and abnormal chest radiography
Authors: L. Corral-Gudino, R. J Jorge-Sanchez, M. Borao-Cengotita-Bengoa, J. Garcia-Aparicio, M. Cascon-Bueno
Journal: BMJ (2009)

A 75 year old woman was admitted to hospital because of dyspnoea. She had been well until nine months previously, when she started to have gradually worsening exertional dyspnoea. On admission, her physical activity was limited. She had no discomfort at rest, but even a very low level of activity caused dyspnoea. She reported no chest pain, orthopnoea, or paroxysmal nocturnal dyspnoea. She had a history of systemic hypertension. She denied smoking. Physical examination showed that she had tachypnoea and a tricuspid systolic murmur. Lung sounds were normal. Electrocardiography showed right axis deviation, right ventricular hypertrophy, and atrial fibrillation. Laboratory evaluation showed polycythaemia. Examination of her chest radiograph at admission provided clues to the diagnosis (fig 1)⇓. Fig 1 Chest radiograph ### Short answer Fig 2 Patient’s chest radiograph showing enlargement of the central pulmonary arteries (arrowheads), with attenuation of the peripheral vessels (arrows)
Primary B‐cell lymphoma and lymphoma‐like lesions of the uterine cervix
Authors: W.Y. Au, B.C.P. Chan, L.P. Chung, C. Choy
Journal: American Journal of Hematology (2003)

Abstract We present three patients with atypical lymphoid cells on cervical smear screening, with diffuse large‐cell B‐cell lymphoma diagnosed by morphology on cervical biopsy. One patient with extensive pelvic disease was treated with chemotherapy and radiotherapy and remained in remission 8 years later. Two patients with presumed stage 1E lesions showed spontaneous regression on repeat cervical biopsy, despite light chain restriction and clonal immunoglobulin gene rearrangement. They are without recurrent malignancy 1 and 5 years after their initial diagnosis. The presence of malignant looking lymphoid cells on cervical smear should be investigated by repeated colposcopic biopsies. The reason for the highly skewed atypical B‐cell lymphoproliferation in lymphoma‐like lesions of the cervix is unknown. With early stage, nonbulky cervical lymphoma in an otherwise healthy patient, a cone biopsy is advised. A number of these lesions may regress even when clonal populations are detected. Am. J. Hematol. 73:176–179, 2003. © 2003 Wiley‐Liss, Inc.
HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers
Authors: Ralph Stadhouders, Suleyman Aktuna, Supat Thongjuea, Ali Aghajanirefah, Farzin Pourfarzad, Wilfred van IJcken, Boris Lenhard, Helen Rooks, Steve Best, Stephan Menzel, Frank Grosveld, Swee Lay Thein, Eric Soler
Journal: Journal of Clinical Investigation (2014)

Genetic studies have identified common variants within the intergenic region (HBS1L-MYB) between GTP-binding elongation factor HBS1L and myeloblastosis oncogene MYB on chromosome 6q that are associated with elevated fetal hemoglobin (HbF) levels and alterations of other clinically important human erythroid traits. It is unclear how these noncoding sequence variants affect multiple erythrocyte characteristics. Here, we determined that several HBS1L-MYB intergenic variants affect regulatory elements that are occupied by key erythroid transcription factors within this region. These elements interact with MYB, a critical regulator of erythroid development and HbF levels. We found that several HBS1L-MYB intergenic variants reduce transcription factor binding, affecting long-range interactions with MYB and MYB expression levels. These data provide a functional explanation for the genetic association of HBS1L-MYB intergenic polymorphisms with human erythroid traits and HbF levels. Our results further designate MYB as a target for therapeutic induction of HbF to ameliorate sickle cell and β-thalassemia disease severity.
Heterogeneous point mutations of the p53 gene in pulmonary fibrosis
Authors: S Hojo, J Fujita, I Yamadori, T Kamei, T Yoshinouchi, Y Ohtsuki, H Okada, S Bandoh, Y Yamaji, J Takahara, T Fukui, M Kinoshita
Journal: European Respiratory Journal (1998)

Lung cancer is a frequent complication in pulmonary fibrosis. Overexpression of p53 proteins has been demonstrated by immunostaining in bronchoepithelial cells in patients with idiopathic pulmonary fibrosis. However, it is still unclear whether this overexpressed p53 protein is wild-type or mutant. It was hypothesized that pulmonary fibrosis may be a precancerous lesion with deoxyribonucleic acid point mutations in bronchoepithelial cells. Mutations of the p53 gene were tested for by fluorescence-based single-strand conformation polymorphism (FSSCP), cloning-sequencing and immunostaining techniques. Out of 10 tissue samples that demonstrated overexpression of p53 protein by immunostaining, nine (90%) exhibited point mutations and eight (80%) exhibited heterogeneous point mutations of the p53 gene. The mutations found in pulmonary fibrosis were scattered throughout the central part of the p53 gene, and both guanine (G):cytosine (C) to adenine (A):thymine (T) and A:T to G:C transitions were frequently observed. In conclusion, frequent heterogeneous point mutations of the p53 gene were detected in pulmonary fibrosis. These mutations may have resulted from several types of deoxyribonucleic acid damage that occurred in bronchoepithelial cells and this may explain previous findings of a very high incidence of lung cancer complicating pulmonary fibrosis.
A significant association exists between the severity of nail and skin involvement in psoriasis
Authors: Zahra Hallaji, Farshad Babaeijandaghi, Mahdi Akbarzadeh, Seydeh Zeinab Seyedi, Massoume Barzegari, Pedram Noormohammadpour, Zohreh Shahabi, Amir Houshang Ehsani
Journal: Journal of the American Academy of Dermatology (2011)
A Hazardous Profession: War, Journalists, and Psychopathology
Authors: Anthony Feinstein, John Owen, Nancy Blair
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: War journalists often confront situations of extreme danger in their work. Despite this, information on their psychological well-being is lacking. METHOD: The authors used self-report questionnaires to assess 140 war journalists, who recorded symptoms of posttraumatic stress disorder (PTSD) (with the Impact of Event Scale—Revised), depression (with the Beck Depression Inventory-II), and psychological distress (with the 28-item General Health Questionnaire). To control for stresses generic to all journalism, the authors used the same instruments to assess 107 journalists who had never covered war. A second phase of the study involved interviews with one in five journalists from both groups, using the Structured Clinical Interview for Axis I DSM-IV Disorders. RESULTS: The rates of response to the self-report questionnaires were approximately 80% for both groups. There were no demographic differences between groups. Both male and female war journalists had significantly higher weekly alcohol consumption. The war journalists had higher scores on the Impact of Event Scale and the Beck Depression Inventory. Their lifetime prevalence of PTSD was 28.6%, and the rates were 21.4% for major depression and 14.3% for substance abuse. War journalists were not, however, more likely to receive treatment for these disorders. CONCLUSIONS: War journalists have significantly more psychiatric difficulties than journalists who do not report on war. In particular, the lifetime prevalence of PTSD is similar to rates reported for combat veterans, while the rate of major depression exceeds that of the general population. These results, which need replicating, should alert news organizations that significant psychological distress may occur in many war journalists and often goes untreated.
The genetic basis of colorectal cancer in a population-based incident cohort with a high rate of familial disease
Authors: M. O. Woods, H. B. Younghusband, P. S. Parfrey, S. Gallinger, J. McLaughlin, E. Dicks, S. Stuckless, A. Pollett, B. Bapat, M. Mrkonjic, A. de la Chapelle, M. Clendenning, S. N. Thibodeau, M. Simms, A. Dohey, P. Williams, D. Robb, C. Searle, J. S. Green, R. C. Green
Journal: Gut (2010)

Colorectal cancer (CRC) is the second most frequent cancer in developed countries. Newfoundland has the highest incidence of CRC in Canada and the highest rate of familial CRC yet reported in the world. To determine the impact of mutations in known CRC susceptibility genes and the contribution of the known pathways to the development of hereditary CRC, an incident cohort of 750 patients with CRC (708 different families) from the Newfoundland population was studied.Microsatellite instability (MSI) testing was performed on tumours, together with immunohistochemistry analysis for mismatch repair (MMR) genes. Where indicated, DNA sequencing and multiplex ligation-dependent probe amplifications of MMR genes and APC was undertaken. DNA from all patients was screened for MUTYH mutations. The presence of the BRAF variant, p.V600E, and of MLH1 promoter methylation was also tested in tumours.4.6% of patients fulfilled the Amsterdam criteria (AC), and an additional 44.6% fulfilled the revised Bethesda criteria. MSI-high (MSI-H) was observed in 10.7% (n=78) of 732 tumours. In 3.6% (n=27) of patients, CRC was attributed to 12 different inherited mutations in six known CRC-related genes associated with chromosomal instability or MSI pathways. Seven patients (0.9%) carried a mutation in APC or biallelic mutations in MUTYH. Of 20 patients (2.7%) with mutations in MMR genes, 14 (70%) had one of two MSH2 founder mutations. 17 of 28 (61%) AC families did not have a genetic cause identified, of which 15 kindreds fulfilled the criteria for familial CRC type X (FCCTX).Founder mutations accounted for only 2.1% of cases and this was insufficient to explain the high rate of familial CRC. Many of the families classified as FCCTX may have highly penetrant mutations segregating in a Mendelian-like manner. These families will be important for identifying additional CRC susceptibility loci.
Effects of interleukin 12 on immune responses and host protection in mice infected with intestinal nematode parasites.
Authors: F D Finkelman, K B Madden, A W Cheever, I M Katona, S C Morris, M K Gately, B R Hubbard, W C Gause, J F Urban
Journal: The Journal of Experimental Medicine (1994)

The cytokine interleukin (IL) 12 stimulates T cell and natural killer cell production of interferon (IFN) gamma and inhibits T cell production of IL-4. We investigated the effects of IL-12 on cytokine gene expression, immunoglobulin (Ig)E, mucosal mast cell, and eosinophil responses, and the course of infection in mice inoculated with the nematode parasite Nippostrongylus brasiliensis, as well as the IFN-gamma dependence of these effects. IL-12 stimulated IFN-gamma and IL-10 gene expression during primary and secondary N. brasiliensis infections and inhibited IL-3, IL-4, IL-5, and IL-9 gene expression during primary infections but had little inhibitory effect during secondary infections. IL-12 inhibited IgE, mucosal mast cell, and blood and tissue eosinophil responses during primary infections, but only eosinophil responses during secondary infections. IL-12 enhanced adult worm survival and egg production during primary, but not secondary infections. IL-12 needed to be administered by day 4 of a primary infection to inhibit IgE and mucosal mast cell responses, and by day 6 to strongly inhibit eosinophil responses and to enhance worm survival and fecundity. Anti-IFN-gamma mAb inhibited the effects of IL-12 on IgE secretion, intestinal mucosal mastocytosis, and parasite survival and fecundity, but did not affect IL-12 inhibition of eosinophilia. These observations indicate that IL-12, if administered during the initiation of eosinophilia. These observations indicate that IL-12, if administered during the initiation of an immune response, can change the response from one that is characterized by the production of T helper (Th)2-associated cytokines to one characterized by the production of Th-1 associated cytokines. However, IL-12 treatment has less of an effect once the production of Th2-associated cytokines has become established. In addition, our results provide evidence that Th2-associated responses protect against, and/or Th1-associated responses exacerbate, nematode infections.
Cerebral Hemodynamics of Experimental Cerebral Embolization
Authors: EUGENE D. ROBIN, FRED FOWLER, ROBERT D. WHALEY, CHARLES H. CRUMP
Journal: Circulation Research (1959)

Cerebral embolization in anesthetized dogs produces a fall in cerebral blood flow but no significant increase in cerebrovascular resistance. The mechanism of the decreased flow is usually a decrease in mean arterial blood pressure. Section of the sympathetic-vagus trunks produces no consistent increase in cerebral blood flow or fall in cerebrovascular resistance.
Mortality Risk Among Children Initially Treated With Dialysis for End-Stage Kidney Disease, 1990-2010
Authors: Mark M. Mitsnefes, Benjamin L. Laskin, Mourad Dahhou, Xun Zhang, Bethany J. Foster
Journal: JAMA (2013)

Importance Most children with end-stage kidney disease (ESKD) are treated with dialysis prior to transplant.It is not known whether their outcomes have changed in recent years. ObjectiveTo determine if all-cause, cardiovascular, and infection-related mortality rates for children and adolescents beginning dialysis improved between 1990 and 2010.Design, Setting, and Participants Retrospective cohort study of patients younger than 21 years initially treated with dialysis for ESKD, recorded in the United States Renal Data System between 1990 and 2010.Children with a prior kidney transplant were excluded.We used Cox proportional hazard models to estimate the hazard ratios (HRs) for mortality associated with a 5-year increment in year of ESKD treatment initiation.Primary analyses censored observation at kidney transplant. Main Outcomes and Measures All-cause, cardiovascular, and infection-related mortality.Results A total of 23 401 children and adolescents who initiated ESKD treatment with dialysis at younger than 21 years between 1990 and 2010 were identified.Crude mortality rates during dialysis treatment were higher among children younger than 5 years at the start of dialysis compared with those who were 5 years and older.Mortality rates for both children and adolescents being treated for ESKD with dialysis decreased significantly between 1990 and 2010.
Mitochondrial complex I defect and increased fatty acid oxidation enhance protein lysine acetylation in the diabetic heart
Authors: Edwin J. Vazquez, Jessica M. Berthiaume, Vasudeva Kamath, Olisaemeka Achike, Elizabeth Buchanan, Monica M. Montano, Margaret P. Chandler, Masaru Miyagi, Mariana G. Rosca
Journal: Cardiovascular Research (2015)

Cardiomyopathy is a major complication of diabetes. Our study was aimed to identify the sites of mitochondrial dysfunction and delineate its consequences on mitochondrial metabolism in a model of type 1 diabetes. Diabetes was induced by streptozotocin injection to male Lewis rats. We found a decrease in mitochondrial biogenesis pathway and electron transport chain complex assembly that targets Complex I. Oxidation of Complex II and long-chain fatty acid substrates support the electron leak and superoxide production. Mitochondrial defects do not limit fatty acid oxidation as the heart's preferred energy source indicating that the diabetic heart has a significant reserve in Complex I- and II-supported ATP production. Both mitochondrial fatty acid oxidation and Complex I defect are responsible for increased protein lysine acetylation despite an unchanged amount of the NAD+-dependent mitochondrial deacetylase sirt3. We quantitatively analysed mitochondrial lysine acetylation post-translational modifications and identified that the extent of lysine acetylation on 54 sites in 22 mitochondrial proteins is higher in diabetes compared with the same sites in the control. The increased lysine acetylation of the mitochondrial trifunctional protein subunit α may be responsible for the increased fatty acid oxidation in the diabetic heart. We identified the specific defective sites in the electron transport chain responsible for the decreased mitochondrial oxidative phosphorylation in the diabetic heart. Mitochondrial protein lysine acetylation is the common consequence of both increased fatty acid oxidation and mitochondrial Complex I defect, and may be responsible for the metabolic inflexibility of the diabetic heart.
ATP-Dependent Mechanism for Coordination of Intercellular Ca <sup>2+</sup> Signaling and Renin Secretion in Rat Juxtaglomerular Cells
Authors: Jian Yao, Michihiro Suwa, Bing Li, Kazuko Kawamura, Tetsuo Morioka, Takashi Oite
Journal: Circulation Research (2003)

A change in intracellular Ca2+ is considered to be the common final signaling pathway through which renin secretion is governed. Therefore, information relating to the generation, control, and processing of Ca2+ signaling in juxtaglomerular cells (JG) will be critical for understanding JG cell behavior. In this study, we investigated the means by which JG cells harmonize their intracellular Ca2+ signals and explored the potential role of these mechanisms in renin secretion. Mechanical stimulation of a single JG cell initiated propagation of an intercellular Ca2+ wave to up to 11.9+/-4.1 surrounding cells, and this was prevented in the presence of the ATP-degrading enzyme, apyrase (1.7+/-0.7 cells), or by desensitization of purinergic receptors via pretreatment of cells with ATP (1.8+/-0.9 cells), thus implicating ATP as a mediator responsible for the propagation of intercellular Ca2+ signaling. Consistent with this, JG cells were demonstrated not to express the gap junction protein connexin43, and neither did they possess functional gap junction communication. Furthermore, massive mechanical stretching of JG cells elicited a 3-fold increase in ATP release. Administration of ATP into isolated perfused rat kidneys induced a rapid, potent, and persistent inhibition of renin secretion, together with a transient elevation of renal vascular resistance. ATP (1 mmol/L) caused up to 79% reduction of the renin secretion activated by lowering the renal perfusion flow (P<0.01). Taken together, our results indicate that under mechanical stimulation, ATP functions as a paracellular mediator to regulate renin secretion, possibly through modulating intra- and intercellular Ca2+ signals.