tbuckley/cabot-search huggingface dataset:
Lessons From Outbreaks of H1N1 Influenza
Authors: Richard A. Stein
Journal: Annals of Internal Medicine (2009)

A new H1N1 triple-reassortant “swine” influenza virus was recently described in individuals from the United States and Mexico who presented with respiratory symptoms, and the same virus was subsequently confirmed in patients from several countries around the world. The circumstances surrounding the emergence of this pathogen, and the factors that facilitated the initial cross-species transmission, are still incompletely understood. It became apparent in the early days of the outbreak that the virus can be directly transmitted between humans. Pathogens that originate in animal reservoirs and subsequently acquire the potential for human-to-human transmission have caused outbreaks throughout human history. Although each outbreak is marked by its own particularities, it is important to remember the teachings that emerge from previous epidemics and pandemics. Integrating the important lessons of the past will provide the best opportunity to understand host–pathogen interaction and the most powerful approach to implementing effective prophylactic and therapeutic measures.
Fall-related injuries during the holiday season--United States, 2000-2003
Authors: Judy A. Stevens, Madhavi Vajani, Usa Prevention
Journal: MMWR Morbidity and Mortality Weekly Report (2004)

Although fall-related injuries occur throughout the year, few studies have analyzed seasonal patterns, and none have examined the extent of such injuries associated with holiday decorating. To characterize nonfatal fall injuries associated with decorating or related activities, CDC analyzed data from the National Electronic Injury Surveillance System All Injury Program (NEISS-AIP) for three winter holiday seasons. This report summarizes the results of that analysis, which indicated that, during 2000-2003, an estimated 17,465 persons were treated in U.S. hospital emergency departments (EDs) for holiday-decorating-related falls. Approximately 62% of those injured were aged 20-49 years; approximately 43% of injuries were caused by falls from ladders; and males were 40% more likely than females to be injured. Prevention strategies should focus on raising awareness about falls and promoting safety practices during the holiday season.
Evolution and Dynamics of Small RNA Response to a Retroelement Invasion in Drosophila
Authors: N. V. Rozhkov, N. G. Schostak, E. S. Zelentsova, I. A. Yushenova, O. G. Zatsepina, M. B. Evgen'ev
Journal: Molecular Biology and Evolution (2012)

Although small RNAs efficiently control transposition activity of most transposons in the host genome, such an immune system is not always applicable against a new transposon's invasions. Here, we explored a possibility to introduce potentially mobile copy of the Penelope retroelement previously implicated in hybrid dysgenesis syndrome in Drosophila virilis into the genomes of two distant Drosophila species. The consequences of such introduction were monitored at different phases after experimental colonization as well as in D. virilis species, which is apparently in the process of ongoing Penelope invasion. We investigated the expression of Penelope and biogenesis of Penelope-derived small RNAs in D. virilis and D. melanogaster strains originally lacking active copies of this element after experimental Penelope invasion. These strains were transformed by constructs containing intact Penelope copies. We show that immediately after transformation, which imitates the first stage of retroelement invasion, Penelope undergoes transposition predominantly in somatic tissues, and may produce siRNAs that are apparently unable to completely silence its activity. However, at the later stages of colonization Penelope copies may jump into one of the piRNA-clusters, which results in production of homologous piRNAs that are maternally deposited and can silence euchromatic transcriptionally active copies of Penelope in trans and, hence, prevent further amplification of the invader in the host genome. Intact Penelope copies and different classes of Penelope-derived small RNAs were found in most geographical strains of D. virilis collected throughout the world. Importantly, all strains of this species containing full-length Penelope tested do not produce gonadal sterility in dysgenic crosses and, hence, exhibit neutral cytotype. To understand whether RNA interference mechanism able to target Penelope operates in related species of the virilis group, we correlated the presence of full-length and potentially active Penelope with the occurrence of piRNAs homologous to this transposable element in the ovaries of species comprising the group. It was demonstrated that Penelope-derived piRNAs are present in all virilis group species containing full-length but transcriptionally silent copies of this element that probably represent the remnants of its previous invasions taking place in the course of the virilis species divergent evolution.
Remission of Substance Use Disorder Among Psychiatric Inpatients With Mental Illness
Authors: Lisa Dixon, Scot McNary, Anthony F. Lehman
Journal: American Journal of Psychiatry (1998)

The authors assessed the nature and stability of remission of substance use disorder among persons with severe mental illness at index hospitalization and at 1-year follow-up.Consecutively admitted inpatients with severe mental illness completed the Structured Clinical Interview for DSM-III-R, Quality of Life Interview, and Addiction Severity Index at admission and 1 year later. Of the 268 patients, 70 were classified as past substance abusers in remission at baseline. Baseline characteristics and 1-year outcomes of this group were compared with those of the 109 current substance abusers and the 89 patients who were not substance abusers.The past abusers were significantly more likely to be women, and they consistently differed significantly from the current abusers in variables involving frequency of drug and alcohol use at baseline. During the follow-up period, the patients with current abuse at baseline were significantly more likely to have recurrences of substance use disorders and to use substance abuse services, and they had significantly more months of alcohol use and alcohol use to excess during follow-up than did the past abusers.Baseline and follow-up assessments suggested that a substantial proportion of severely mentally ill patients with past substance use disorders are in stable remission.
Down-regulation of mannosyl receptor-mediated endocytosis and antigen F4/80 in bacillus calmette-guerin-activated mouse macrophages. Role of T lymphocytes and lymphokines
Authors: AB Ezekowitz, S Gordon
Journal: The Journal of Experimental Medicine (1982)

Bacillus Calmette-Guerin (BCG) infection alters the surface and endocytic properties of mouse peritoneal macrophages (PM) compared with thioglycollate- elicited (TPM) or resident PM (RPM). Expression of Ia antigen (Ag) is enhanced up to fourfold, but plasma membrane receptors that mediate binding and uptake of mannosyl/fucosyl-terminated glycoconjugates (MFR), Fc receptors, and the macrophage (mφ)-specific Ag F4/80 are reduced by 50-80 percent. Levels of Mac-1 remain relatively stable. These changes are accompanied by enhanced secretion of O(2)(-), after further stimulation with phorbyl myristate acetate, and of plasminogen activator. Both these products are released by TPM, but not RPM. The characteristic surface phenotype of BCG-PM can also be induced by injection of C. parvum, another mφ- activating agent, but not by thioglycollate broth, lipopolysaccharide, or proteose peptone. Purified protein derivative (PPD) and N-acetylmuramyl-L- alanyl-D-isoglutamine. 2H(2)0 are soluble agents with partial activity. Alteration of mφ markers by BCG infection depends on T lymphocyte function, although studies with nude mice indicate that other pathways may also serve to modify the surface of the mφ. Mφ from uninfected animals displayed all markers of activation after adoptive transfer of specifically-sensitised lymphocytes with PPD, intraperitoneally, or after co- cultivation. Treatment of primed lymphocytes with anti-Thy-1 antibody and complement ablated this effect. Lymphokines obtaned by Ag or mitogen stimulation induced similar changes in TPM and RPM. Mannose-specific endocytosis decayed rapidly, time 1/2 approximately equal to 16 h and stabilized at approximately 25 percent of control values. Single-cell analysis showed that residual MFR activity was uniform in the target population. Loss of Ag F4/80 after activation by lymphocyte and PPD was less marked than after infection (35 percent vs 80 percent), unlike MFR activity, which declined to a similar extent. Induction of mφ Ia by lymphokine reached a peak after 2-3 d and was lost within 2 d of its removal. Recovery of MFR and F4/80 was incomplete under these conditions. These studies establish that activated mφ known to display enhanced antimicrobial/anticellular activity express markedly different surface properties distinct from elicited or resident cells. The role of antigen- stimulated T cell products in regulating mφ function is confirmed, and down-regulation of mannosyl-receptor-mediated endocytosis provides a sensitive, quantitative, and cell-specific new marker to study their properties and mechanism of action. Extensive, but selective remodeling of mφ plasma membrane structure could play an important role in controlling recognition and effector mechanisms of the activated mφ.
Inflammation caused by radiofrequency ablation for lung cancer is worse after radiotherapy and in large tumours
Authors: S Roy-Choudhury
Journal: Thorax (2008)

The use of radiofrequency ablation (RFA) of solid primary and metastatic pulmonary tumours in poor-risk surgical patients is increasing. The authors report on percutaneous RFA with particular reference to inflammation-related complications in a series of 130 patients undergoing 327 ablation sessions using C-reactive protein (CRP) as a marker for inflammation. RFA was performed with CT guidance using the internally-cooled impedance-modulated Cool Tip system (Valleylab, …
CXCL5 Regulates Chemokine Scavenging and Pulmonary Host Defense to Bacterial Infection
Authors: Junjie Mei, Yuhong Liu, Ning Dai, Michael Favara, Teshell Greene, Samithamby Jeyaseelan, Mortimer Poncz, Janet S. Lee, G. Scott Worthen
Journal: Immunity (2010)
Radiological sacroiliitis, a hallmark of spondylitis, is linked with CARD15 gene polymorphisms in patients with Crohn's disease
Authors: H Peeters, B Vander Cruyssen, D Laukens, P Coucke, D Marichal, M Van Den Berghe, C Cuvelier, E Remaut, H Mielants, F De Keyser, M D Vos
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Sacroiliitis is a common extraintestinal manifestation of Crohn's disease but its association with the HLA-B27 phenotype is less evident. Polymorphisms in the CARD15 gene have been linked to higher susceptibility for Crohn's disease. In particular, associations have been found with ileal and fibrostenosing disease, young age at onset of disease, and familial cases. <b>Objectives:</b> To investigate whether the presence of sacroiliitis in patients with Crohn's disease is linked to the carriage of CARD15 polymorphisms. <b>Methods:</b> 102 consecutive patients with Crohn's disease were clinically evaluated by a rheumatologist. Radiographs of the sacroiliac joints were taken and assessed blindly by two investigators. The RFLP-PCR technique was used to genotype all patients for three single nucleotide polymorphisms (SNP) in the CARD15 gene. Every SNP was verified by direct sequencing. The HLA-B27 phenotype was determined. <b>Results:</b> Radiological evidence of sacroiliitis with or without ankylosing spondylitis was found in 23 patients (23%), of whom only three were HLA-B27 positive. In contrast, 78% of patients with sacroiliitis carried a CARD15 variant <i>v</i> 48% of those without sacroiliitis (p = 0.01; odds ratio 3.8 (95% confidence interval, 1.3 to 11.5)). Multivariate analysis (logistic regression) showed that the association between sacroiliitis and CARD15 polymorphisms was independent of other CARD15 related phenotypes (ileal and fibrostenosing disease, young age at onset of disease, familial Crohn's disease) (p = 0.039). <b>Conclusions:</b> CARD15 variants were identified as genetic predictors of Crohn's disease related sacroiliitis. An association was demonstrated between these polymorphisms and an extraintestinal manifestation of Crohn's disease.
Targeting Glucose in Acute Myocardial Infarction
Authors: Ajay Chaudhuri, Michael Miller, Richard Nesto, Noah Rosenberg, Paresh Dandona
Journal: Diabetes Care (2007)

Proinflammatory mechanisms may contribute to hyperglycemia-associated adverse outcomes in acute myocardial infarction (AMI) (1–3). Insulin exerts anti-inflammatory effects in ST elevation myocardial infarction and coronary artery bypass graft patients (4–6). Inflammation plays an important role in the pathogenesis of atherosclerosis and thrombosis (7,8). Thus, insulin infusion in AMI should be beneficial. However, glucose, insulin, and potassium (GIK) infusion was neutral in its benefit in the Clinical Trial of Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation–Estudios Cardiologicos Latinoamerica (CREATE-ECLA) study (9).

The GIK regimen (fixed combination of 1 l of 25% dextrose with 50 units regular insulin and 80 meq/l potassium) used in CREATE-ECLA is known to lower serum free fatty acid concentrations (10) and to reduce mortality by 18% in AMI, as previously reviewed (11). However, the infusion of 30 g/h glucose without titration of glucose or insulin in CREATE-ECLA led to a significant increase in blood glucose concentrations. Mehta et al. suggested that the adverse effect of GIK-induced hyperglycemia may have neutralized any potential benefit of insulin in the GIK regimen. However, Mehta et al. did not comment on the magnitude of the potential contribution of hyperglycemia to neutralize benefits of GIK. Since admission hyperglycemia was predictive of mortality in AMI in CREATE-ECLA, we have estimated the potential effects of GIK-induced hyperglycemia on mortality in this study.

Based on the admission blood …
The mouse with trisomy 16 as a model of human hearts with common atrioventricular junction
Authors: R Anderson
Journal: Cardiovascular Research (1998)

Objective: To establish if the mouse with trisomy 16 is a suitable animal model with which to elucidate the development of a common atrioventricular junction. Methods: The junctional morphologies in the normal human heart and those with a common atrioventricular junction are compared and contrasted. These are then related to observations made in normal mice and those with trisomy 16. So as better to understand development, a full description is given first of the normal atrioventricular junctions. Developmental implications are discussed because failure of fusion of the endocardial cushions cannot account for all the anomalies found in RXR alpha knockout, and in iv/iv mice. Results: Mice with trisomy 16 showed evidence of deficiencies of atrioventicular septation and possessed a common atrioventricular junction, but the valvar orifices were not balanced between the ventricles as is the case in humans. Whilst some mice showed affinities with human tricuspid atresia, other cardiac malformations in the mice had no counterparts in human cardiac pathology. In humans both “partial” and “complete” forms of “atrioventricular canal malformations” share a basically common muscular junctional morphology, the differences being due exclusively to the way the bridging leaflets are fused to each other and/or the septum. Conclusions: It is simplistic to use the mouse with trisomy 16 as a model for cardiac abnormalities seen in humans. A spectrum more comparable to humans is found in RXR knockout mice. Study of the iv/iv mouse may help elucidate the genetic steps involved in normal and abnormal atrioventricular septation.
Prognosis in Kaposi's Sarcoma 2
Authors: A. C. Templeton, D. Bhana
Journal: JNCI Journal of the National Cancer Institute (1975)

We studied and followed up 112 African patients with Kaposi's sarcoma for at least 3 years or until death to determine what features of the disease at presentation most accurately predicted the prognosis. The clinical pattern of disease at presentation was most important. All patients with generalized disease died of their disease; the only deaths among those with nodular disease were due to intercurrent illness. The 3-year survuval rate among patients with locally aggressive lesions with 64%. We could obtain greater refinement of prognosis by noting the response to a dinitrochlorobenzene challenge, the presence of nodal involvement, and the histologic pattern of the tumor. The age and sex of the patient influenced the pattern of disease likely to be found, but the prognosis for a given clinical pattern was the same in both sexes and at different ages.
Does commitment theory explain non-kin altruism in religious contexts?
Authors: Hector N. Qirko
Journal: Behavioral and Brain Sciences (2004)

Atran &amp; Norenzayan (A&amp;N) fail to address several problems with commitment theory as it relates to non-kin altruism in religious contexts. They (1) provide little support for the contention that religious sacrifices function as signals, (2) do not distinguish between religious specialists and lay believers, and (3) conflate definitions of cooperation and sacrifice.
Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration.
Authors: M Clauss, M Gerlach, H Gerlach, J Brett, F Wang, P C Familletti, Y C Pan, J V Olander, D T Connolly, D Stern
Journal: The Journal of Experimental Medicine (1990)

Systemic infusion of low concentrations of tumor necrosis factor/cachectin (TNF) into mice that bear TNF-sensitive tumors leads to activation of coagulation, fibrin formation, and occlusive thrombosis exclusively within the tumor vascular bed. To identify mechanisms underlying the localization of this vascular procoagulant response, a tumor-derived polypeptide has been purified to homogeneity from supernatants of murine methylcholanthrene A-induced fibrosarcomas that induces endothelial tissue factor synthesis and expression (half-maximal response at approximately 300 pM), and augments the procoagulant response to TNF in a synergistic fashion. This tumor-derived polypeptide was identified as the murine homologue of vascular permeability factor (VPF) based on similar mobility on SDS-PAGE, an homologous NH2-terminal amino acid sequence, and recognition by a monospecific antibody to guinea pig VPF. In addition, VPF was shown to induce monocyte activation, as evidenced by expression of tissue factor. Finally, VPF was shown to induce monocyte chemotaxis across collagen membranes and endothelial cell monolayers. Taken together, these results indicate that VPF can modulate the coagulant properties of endothelium and monocytes, and can promote monocyte migration into the tumor bed. This suggests one mechanism through which tumor-derived mediators can alter properties of the vessel wall.
The <i>In vitro</i> and <i>In vivo</i> Effects of JNJ-7706621: A Dual Inhibitor of Cyclin-Dependent Kinases and Aurora Kinases
Authors: Stuart Emanuel, Catherine A. Rugg, Robert H. Gruninger, Ronghui Lin, Angel Fuentes-Pesquera, Peter J. Connolly, Steven K. Wetter, Beth Hollister, Walter W. Kruger, Cheryl Napier, Linda Jolliffe, Steven A. Middleton
Journal: Cancer Research (2005)

Modulation of aberrant cell cycle regulation is a potential therapeutic strategy applicable to a wide range of tumor types. JNJ-7706621 is a novel cell cycle inhibitor that showed potent inhibition of several cyclin-dependent kinases (CDK) and Aurora kinases and selectively blocked proliferation of tumor cells of various origins but was about 10-fold less effective at inhibiting normal human cell growth in vitro. In human cancer cells, treatment with JNJ-7706621 inhibited cell growth independent of p53, retinoblastoma, or P-glycoprotein status; activated apoptosis; and reduced colony formation. At low concentrations, JNJ-7706621 slowed the growth of cells and at higher concentrations induced cytotoxicity. Inhibition of CDK1 kinase activity, altered CDK1 phosphorylation status, and interference with downstream substrates such as retinoblastoma were also shown in human tumor cells following drug treatment. Flow cytometric analysis of DNA content showed that JNJ-7706621 delayed progression through G1 and arrested the cell cycle at the G2-M phase. Additional cellular effects due to inhibition of Aurora kinases included endoreduplication and inhibition of histone H3 phosphorylation. In a human tumor xenograft model, several intermittent dosing schedules were identified that produced significant antitumor activity. There was a direct correlation between total cumulative dose given and antitumor effect regardless of the dosing schedule. These results show the therapeutic potential of this novel cell cycle inhibitor and support clinical evaluation of JNJ-7706621.
The Elusiveness of Population-Wide High Blood Pressure Control
Authors: Paul K. Whelton
Journal: Annual Review of Public Health (2015)

High blood pressure (hypertension) is a leading risk factor for cardiovascular disease. It is highly prevalent in the US general population, especially in those who are old, African American, or socially disadvantaged. Prevalence is also high and increasing worldwide. Awareness, treatment, and control of hypertension have improved over time, but there is still considerable room for improvement. The optimal solution to this health challenge varies by country. Several nonpharmacologic and pharmacologic interventions are well proven as effective means to prevent hypertension and improve control rates in those with established hypertension. Better prevention and control of hypertension will yield substantial general population health benefits and remain high priorities in public health.
Calcium and potassium currents in cells from adult and aged canine right atria
Authors: W Dun
Journal: Cardiovascular Research (2003)

Action potential (AP) contours vary considerably between normal adult and aged right atrial fibers. The ionic bases for these differences remain unknown. Therefore we studied Ca(2+) and K(+) currents in cells from adult and aged canine right atria (RA).We used whole cell patch clamp recording techniques to measure L-type Ca(2+) currents (I(CaL)) with either Ca(2+) or Ba(2+) (3 mM) as the charge carrier, and both the transient outward (I(to)) and sustained potassium currents (I(sus)) in cells dispersed from normal adult (Adult, 2-5 years) and older dogs (Aged, >8 years). There is a significant reduction in peak I(CaL) (47%) and I(BaL) (43%) in Aged cells, yet differences in I(BaL) disappear with maximal beta adrenergic stimulation (isoproterenol, 1 microM). Composite I(to) and I(sus) densities were significantly increased in the Aged versus Adult cell group (by 31 and 27% at +50 mV, respectively). I(to) decay during a maintained depolarization was slowed in Aged cells. Furthermore, I(to) steady-state inactivation curve was shifted positively in Aged cells. Finally, composite I(to) and I(sus) currents of Aged cells were more sensitive to tetraethylammonium chloride (TEA), a specific inhibitor of some types of K(+) currents. In the presence of TEA (5 mM), I(to) in Aged cells was significantly greater than that in Adult cells.Ionic currents differ in Aged versus Adult right atrial cells, such that a reduced Ca(2+) current and augmented outward currents could contribute significantly to the altered AP contour of the Aged RA cell. Adrenergic stimulation appears to restore Ba(2+) currents in Aged cells. Finally, an augmented TEA sensitive current plays a role in changes of I(sus) in Aged right atrial cells.