tbuckley/cabot-search huggingface dataset:
C-reactive protein mediates the solubilization of nuclear DNA by complement in vitro.
Authors: F A Robey, K D Jones, A D Steinberg
Journal: The Journal of Experimental Medicine (1985)

We have studied the interaction of C-reactive protein (CRP)-chromatin complexes with serum. The amount of chromatin solubilized by serum is directly proportional to the amount of CRP present. Serum minus C3 did not appreciably solubilize chromatin within the time allowed in these experiments regardless of the amount of CRP present. This indicates that, in addition to CRP, complement is critical to the solubilization process. Studies using genetically C2-deficient serum and purified C2 indicate that the classical complement pathway is primarily involved in the solubilization, however, there may be minor involvement by the alternative pathway. We used an enzyme-linked immunosorbent assay to determine the amounts of CRP in plasma from eight patients with systemic lupus erythematosus; two of the eight had levels of CRP far lower than previously reported for normal individuals, and an additional sample had antibodies reactive with CRP. Together, these results suggest that one of the functions of CRP is to mediate the removal of exposed nuclear DNA by complement-dependent solubilization of chromatin. A defect in this mechanism could (a) facilitate the production of antibodies against chromatin components exposed due to tissue damage or (b) contribute to immune complexes containing the chromatin components released from damaged tissue because they are not rapidly cleared.
Cardiac Troponin I Is Associated With Impaired Hemodynamics, Progressive Left Ventricular Dysfunction, and Increased Mortality Rates in Advanced Heart Failure
Authors: Tamara B. Horwich, Jignesh Patel, W. Robb MacLellan, Gregg C. Fonarow
Journal: Circulation (2003)

Cardiac troponin I (cTnI), a sensitive and specific marker of myocardial cell injury, is useful in diagnosing and assessing prognosis in acute coronary syndromes. Small studies report that cTnI is elevated in severe heart failure (HF) and may predict adverse outcomes.The present study evaluated 238 patients with advanced HF referred for cardiac transplantation evaluation who had cTnI assay drawn at the time of initial presentation. Patients with acute myocardial infarction or myocarditis were excluded from analysis. cTnI was detectable (cTnI > or =0.04 ng/mL) in serum of 117 patients (49.1%). Patients with detectable cTnI levels had significantly higher B-type natriuretic peptide (BNP) levels (P<0.001) and more impaired hemodynamic profiles, including higher pulmonary wedge pressures (P=0.002) and lower cardiac indexes (P<0.0001). A significant correlation was found between detectable cTnI and progressive decline in ejection fraction over time. Furthermore, detectable cTnI was associated with increased mortality risk (RR, 2.05; 95% CI, 1.22 to 3.43). After adjustment for other factors associated with adverse prognosis including age, sex, ejection fraction, and coronary artery disease, cTnI remained a significant predictor of death. cTnI used in conjunction with BNP further improved prognostic value.cTnI is associated with impaired hemodynamics, elevated BNP levels, and progressive left ventricular dysfunction in patients with HF. cTnI may be a novel, useful tool in identifying patients with HF who are at increased risk for progressive ventricular dysfunction and death.
Complement Membrane Attack Complex (C5b-9) Mediates Interstitial Disease in Experimental Nephrotic Syndrome
Authors: MASAOMI NANGAKU, JEFF PIPPIN, WILLIAM G. COUSER
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Accumulating evidence suggests that the generation of complement activation products from filtered complement components in urine with nonselective proteinuria leads to tubulointerstitial disease, resulting in progressive loss of renal function. To elucidate the role of C5b-9 in complement-mediated effects on renal tubular cells exposed to proteinuric urine, equivalent levels of proteinuria were induced (using the aminonucleoside of puromycin) in normocomplementemic and genetically C6-deficient piebald viral glaxo (PVG) rats. Semi-quantitative histologic analysis revealed that complement-sufficient animals developed more severe tubulointerstitial disease than did C6-deficient rats. Amelioration of tubulointerstitial damage in C6-deficient animals was confirmed by studies with three independent markers of tubular damage, i.e., vimentin, osteopontin, and proliferating cell nuclear antigen. More tubular epithelial cells expressed osteopontin (an early marker of tubular injury) in normocomplementemic rats, compared with C6-deficient rats, at both days 7 and 12. Staining of vimentin in the tubules, near areas of tubular damage, was increased in normocomplementemic rats at day 12, and more proliferating cell nuclear antigen-positive tubular cells were observed at day 12 in complement-sufficient animals. The tubulointerstitial damage in complement-sufficient rats was also associated with greater accumulation of extracellular matrix (fibronectin) at day 12. These studies document for the first time an important role for C6, and therefore C5b-9, in the pathogenesis of non-immunologic tubulointerstitial injury induced by proteinuria. These findings suggests that C5b-9 formation resulting from proteinuria contributes to the loss of nephron function by damaging the tubulointerstitium and that prevention of C5b-9 formation in tubules could slow the deterioration of renal function.
Clinical Features of Bipolar Depression Versus Major Depressive Disorder in Large Multicenter Trials
Authors: Roy H Perlis, Eileen Brown, Robert W Baker, Andrew A Nierenberg
Journal: American Journal of Psychiatry (2006)

Failure to recognize bipolar disorder in patients who experience a major depressive episode may lead to inappropriate treatment and poorer outcomes. Clinical features that could distinguish bipolar from unipolar depression would facilitate more appropriate treatment selection.The authors used data from nonpsychotic outpatients participating in three large multicenter clinical trials conducted in the United States for the treatment of major depressive episodes to compare 477 subjects with a diagnosis of bipolar disorder and 1,074 with major depressive disorder.Bipolar depression was associated with family history of bipolar disorder, an earlier age at onset, a greater previous number of depressive episodes, and eight individual symptom items on the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale. Fears were more common in patients with bipolar disorder, whereas sadness; insomnia; intellectual (cognitive), somatic (muscular), respiratory, genitourinary complaints; and depressed behavior were more common in patients with unipolar depression. A logistic regression model correctly classified 86.9% of the subjects.Bipolar depression and major depressive disorder exhibit subtle differences in presentation, which may help guide the initial diagnosis.
Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)–associated inflammatory diseases
Authors: Dirk Holzinger, Selina Kathleen Fassl, Wilco de Jager, Peter Lohse, Ute F. Röhrig, Marco Gattorno, Alessia Omenetti, Sabrina Chiesa, Francesca Schena, Judith Austermann, Thomas Vogl, Douglas B. Kuhns, Steven M. Holland, Carlos Rodríguez-Gallego, Ricardo López-Almaraz, Juan I. Arostegui, Elena Colino, Rosa Roldan, Smaragdi Fessatou, Bertrand Isidor, Sylvaine Poignant, Koichi Ito, Hans-Joerg Epple, Jonathan A. Bernstein, Michael Jeng, Jennifer Frankovich, Geraldina Lionetti, Joseph A. Church, Peck Y. Ong, Mona LaPlant, Mario Abinun, Rod Skinner, Venetia Bigley, Ulrich J. Sachs, Claas Hinze, Esther Hoppenreijs, Jan Ehrchen, Dirk Foell, Jae Jin Chae, Amanda Ombrello, Ivona Aksentijevich, Cord Sunderkoetter, Johannes Roth
Journal: Journal of Allergy and Clinical Immunology (2015)
Complement Factor H Y402H and C-Reactive Protein Polymorphism and Photodynamic Therapy Response in Age-Related Macular Degeneration
Authors: Xuefeng Feng, Jing Xiao, Brooke Longville, Alexander X.J. Tan, Xia Ni Wu, Matthew N. Cooper, Ian L. McAllister, Timothy Isaacs, Lyle J. Palmer, Ian J. Constable
Journal: Ophthalmology (2009)
Medical cover at Scottish football matches: have the recommendations of the Gibson Report been met?
Authors: G W Kerr, S C Wilkie, C A McGuffie
Journal: British Journal of Sports Medicine (1999)

To determine if doctors providing medical care at Scottish football stadiums meet the standards recommended by the Gibson Report.A postal questionnaire and telephone follow up of doctors involved with the 40 Scottish League teams.47% of the doctors had not attended any relevant resuscitation courses and 72% had no training in major incident management.The recommendations of the Gibson Report with regard to medical cover at football stadiums have not been fully implemented in Scotland.
Homocysteine and endothelial function
Authors: S Doshi
Journal: Cardiovascular Research (1999)

See article of Lambert et al. [34] (pages 743–751) in this issue. 

The hypothesis that homocysteine may cause vascular disease was originally proposed by McCully, following the observation that premature thromboembolism and atherosclerosis was a feature of homocystinuria [1]. In homocystinuria, a rare inborn error of metabolism, plasma homocysteine concentrations are generally 10 to 50 times that found in the healthy population [2]. This led to the hypothesis that mild to moderate elevations of plasma homocysteine may be a risk factor for atherosclerosis in the general population. This hypothesis has generated considerable interest, particularly as simple therapy with oral B group vitamins significantly lowers plasma homocysteine [3].

Homocysteine is a thiol containing amino acid that is metabolised from methionine, an essential amino acid derived from dietary protein. Homocysteine can be metabolised further to cysteine by transsulfuration (using vitamin B6 as cofactor) or remethylated back to methionine using either methyltetrahydrofolate (and Vit B12 as cofactor) or betaine as co-substrate (see Fig. 1). In human plasma, homocysteine exists in several forms. Approximately 70–80% is bound to protein, mainly albumin, by a disulphide bond. The remaining homocysteine oxidises to form dimers (homocystine) or combines with cysteine to form a mixed disulphide. Only a small proportion (<1%) circulates as free homocysteine. A number of techniques are now available for the combined measurement of the multiple forms of plasma homocysteine, which is expressed as total homocysteine (tHcy) [4].



Fig. 1 
Metabolism of homocysteine.



A ‘normal’ range for tHcy cannot be defined but various studies report fasting levels in the range 5–15 μmol/l in the healthy population. A number of factors, genetic and acquired, can influence the blood levels of tHcy. Genetic factors include the genotype for methylene tetrahydrofolate reductase (MTHFR) C677T mutation, which results in thermolability, reduced activity and consequently fasting hyperhomocysteinaemia, particularly … 

* Corresponding author. Tel.: +44-1222-744-851; fax: +44-1222-766-276
Montelukast during Primary Infection Prevents Airway Hyperresponsiveness and Inflammation after Reinfection with Respiratory Syncytial Virus
Authors: Junyan Han, Yi Jia, Katsuyuki Takeda, Yoshiki Shiraishi, Masakazu Okamoto, Azzeddine Dakhama, Erwin W. Gelfand
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Respiratory syncytial virus (RSV) bronchiolitis in infants may be followed by the development of asthma-like symptoms. Age at first infection dictates consequences upon reinfection. Reinfection of mice initially exposed as neonates to RSV enhanced development of airway hyperresponsiveness (AHR), eosinophilic inflammation, and mucus hyperproduction. RSV lower respiratory tract disease is associated with activation of the leukotriene pathway.
Efficacy and safety of recombinant human parathyroid hormone (1–84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study
Authors: Michael Mannstadt, Bart L Clarke, Tamara Vokes, Maria Luisa Brandi, Lakshminarayan Ranganath, William D Fraser, Peter Lakatos, Laszlo Bajnok, Roger Garceau, Leif Mosekilde, Hjalmar Lagast, Dolores Shoback, John P Bilezikian
Journal: The Lancet Diabetes & Endocrinology (2013)
Declines in Acute Myocardial Infarction After Smoke-Free Laws and Individual Risk Attributable to Secondhand Smoke
Authors: James M. Lightwood, Stanton A. Glantz
Journal: Circulation (2009)

Background— The estimated effects of recent pubic and workplace smoking restriction laws suggest that they produce significant declines in community rates of heart attack. The consistency of these declines with existing estimates of the relative risk of heart attack in individuals attributable to passive smoking exposure is poorly understood. The objective is to determine the consistency of estimates of reductions in community rates of heart attacks resulting from smoking restriction laws with estimates of the relative risk of heart disease in individuals exposed to passive smoking. Methods and Results— Meta-analyses of existing estimates of declines in community rates were compared with a mathematical model of the relationship between individual risk and community rates. The outcome measure is the ratio of community rates of acute myocardial infarction (after divided by before implementation of a smoking restriction law). There is a significant drop in the rate of acute myocardial infarction hospital admissions associated with the implementation of strong smoke-free legislation. The primary reason for heterogeneity in results of different studies is the duration of follow-up after adoption of the law. The pooled random-effects estimate of the rate of acute myocardial infarction hospitalization 12 months after implementation of the law is 0.83 (95% confidence interval, 0.80 to 0.87), and this benefit grows with time. This drop in admissions is consistent with a range of plausible individual risk and exposure scenarios. Conclusion— Passage of strong smoke-free legislation produces rapid and substantial benefits in terms of reduced acute myocardial infarctions, and these benefits grow with time.
Delinquency and Mortality: A 50-Year Follow-Up Study of 1,000 Delinquent and Nondelinquent Boys
Authors: J H Laub, G E Vaillant
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: It is well established that until age 40 years, delinquent individuals have roughly twice the mortality of nondelinquent individuals and that the excess deaths are largely due to accidents, violence, and substance abuse. The present study examined if the increased mortality of delinquent subjects continues until age 65 years and, if so, why. METHOD: The authors followed 475 delinquent and 456 matched nondelinquent comparison boys from age 14 years until age 65 years. RESULTS: Thirteen percent (N=62) of the delinquent and only 6% (N=28) of the nondelinquent subjects died unnatural deaths. By age 65 years, 29% (N=139) of the delinquent and 21% (N=95) of the nondelinquent subjects had died from natural causes. In a univariate analysis, frequency of delinquency, abuse of alcohol, adult crime, dysfunctional home environment, and poor education were significantly related to death, especially to unnatural death. However, when delinquency and alcohol abuse were controlled by logistic regression, education, dysfunctional upbringing, and adult criminality made no further contributions to mortality. CONCLUSIONS: Although delinquency is strongly associated with premature mortality, the etiological links remain unclear. Alcohol abuse and poor self-care in adulthood (e.g., infections or accidents) account for most of the modest variance in mortality that could be accounted for.
High resolution mapping in the major histocompatibility complex region identifies multiple independent novel loci for psoriatic arthritis
Authors: Proton Rahman, Nicole M Roslin, Fawnda J Pellett, Mathieu Lemire, Celia M T Greenwood, Joseph Beyene, Angela Pope, Lynette Peddle, Andrew D Paterson, Mohammed Uddin, Dafna D Gladman
Journal: Annals of the Rheumatic Diseases (2011)

Objective Psoriatic arthritis (PsA) has a clear familial predisposition, the major histocompatibility complex (MHC) region being the strongest genetic locus. The study primary objective was to identify single nucleotide polymorphisms (SNPs) independent of known human leucocyte antigen (HLA) alleles within the MHC region that are associated with PsA using a high-density SNP map. Method In all, 914 samples were assessed, including 427 PsA cases from 2 well established PsA cohorts and 487 controls from Canada. The genotype data consisted of 2521 SNPs from 2 Illumina Goldengate MHC panels, spanning 4.9 Mb of chromosome 6 with an average spacing of 2 kb. Classical HLA alleles were genotyped in all subjects using sequence-specific oligonucleotide probes or sequence-specific primers. A conditioning approach was used to distinguish between new associations and those in linkage disequilibrium (LD) with known HLA alleles. Results Unconditional association analysis revealed 43 markers with p&lt;7.26×10 −5 (calculated experiment-wide significance threshold). In the conditional analysis, 10 SNPs showed statistically significant association at a threshold of p&lt;7.26×10 −5 . Seven SNPs were in strong LD in the study data (pairwise r 2 &gt;0.77 in the controls) reflecting one association signal. These SNPs spanned a 1.6 Mb region. SNP rs1150735 is 1.5 kb upstream from ring finger protein 39 (RNF39). RNF39 SNPs have been associated with HIV1 disease progression and set point CD4 T cell count. Conclusion Four new loci for either psoriasis or PsA in the MHC region that are independent of known HLA alleles have been identified. The effect size of these variants is modest. Replication of these variants in multiple larger populations is necessary.
Human rights group calls on Israel to save Palestinian health services
Authors: Donald Macintyre
Journal: BMJ (2006)

Two eminent Israeli doctors have called on their government to take immediate action to prevent the collapse of health services in Gaza and the West Bank in the wake of the international and Israeli boycott of the Hamas led Palestinian Authority.

Rafi Walden, head of surgery and assistant director at Sheba Hospital, and Zvi Bentwich, an epidemiologist who founded Israel's first AIDS clinic, warned that Palestinian health services were facing a full scale “emergency” because of the funding cuts by Israel and donor countries.

Both professors are board members of Physicians for Human Rights-Israel, which produced a report last week warning that the occupied territories face a “humanitarian disaster” because …
METHIONINE PROTECTS AGAINST MAPHARSEN LIVER INJURY IN PROTEIN-DEPLETED DOGS
Authors: J. P. B. Goodell, P. C. Hanson, W. B. Hawkins
Journal: The Journal of Experimental Medicine (1944)

Depletion of body protein stores by means of low protein diet or plasmapheresis causes greater susceptibility to liver injury by the arsenical compound, mapharsen. Normal dogs can tolerate mapharsen in doses of 0.006 to 0.008 gm. per kilo whereas in protein-depleted dogs doses of 0.002 to 0.0025 gm. per kilo cause liver injury with jaundice. Methionine (2 to 4 gm.) given by mouth 20 to 24 hours prior to administration of mapharsen is protective and the dogs will tolerate 0.0045 gm. per kilo with no icterus developing. Methionine (1 gm.) intravenously just prior to mapharsen injection is not as consistent in effecting protection, but the smaller dose may be responsible.
Genotype-phenotype correlation for pulmonary function in cystic fibrosis
Authors: J de Gracia
Journal: Thorax (2005)

Background: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). Methods: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I–II/I–II, I–II/III–V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. Results: Seventy four patients were included in the study. Patients with genotype I–II/I–II had significantly lower current spirometric values (p<0.001), greater loss of pulmonary function (p<0.04), a higher proportion of end-stage lung disease (p<0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I–II/III, I–II/IV and I–II/V (p<0.001). Conclusions: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.
Erythrocyte sedimentation rate (ESR) as diagnostic test for Budd-Chiari syndrome?
Authors: T. Vanasek, P. Dulicek, P. Hulek, P. Loudova, A. Krajina, J. Zizka, T. Fejfar, O. Pozler, M. Lojik, M. Volfova, I. Hruba
Journal: Journal of Hepatology (2001)
The Combination of Genetic Instability and Clonal Expansion Predicts Progression to Esophageal Adenocarcinoma
Authors: Carlo C. Maley, Patricia C. Galipeau, Xiaohong Li, Carissa A. Sanchez, Thomas G. Paulson, Patricia L. Blount, Brian J. Reid
Journal: Cancer Research (2004)

Abstract There is debate in the literature over the relative importance of genetic instability and clonal expansion during progression to cancer. Barrett’s esophagus is a uniquely suited model to investigate neoplastic progression prospectively because periodic endoscopic biopsy surveillance is recommended for early detection of esophageal adenocarcinoma. We hypothesized that expansion of clones with genetic instability would predict progression to esophageal adenocarcinoma. We measured p16 (CDKN2A/INK4A) lesions (loss of heterozygosity, mutations, and CpG island methylation), p53 (TP53) lesions (loss of heterozygosity, mutation) and ploidy abnormalities (aneuploidy, tetraploidy) within each Barrett’s esophagus segment of a cohort of 267 research participants, who were followed prospectively with cancer as an outcome. We defined the size of a lesion as the fraction of cells with the lesion multiplied by the length of the Barrett’s esophagus segment. A Cox proportional hazards regression indicates that the sizes of clones with p53 loss of heterozygosity (relative risk = 1.27x for an x cm clone; 95% confidence interval, 1.07–1.50) or ploidy abnormalities (relative risk = 1.31x for an x cm clone; 95% confidence interval, 1.07–1.60) predict progression to esophageal adenocarcinoma better than the mere presence of such clones (likelihood ratio test, P &amp;lt; 0.01). Controlling for length of the Barrett’s esophagus segment had little effect. The size of a clone with a p16 lesion is not a significant predictor of esophageal adenocarcinoma when we controlled for p53 loss of heterozygosity status. The combination of clonal expansion and genetic instability is a better predictor of cancer outcome than either alone. This implies that interventions that limit expansion of genetically unstable clones may reduce risk of progression to cancer.