tbuckley/cabot-search huggingface dataset:
Of mice and men: comparative proteomics of bronchoalveolar fluid
Authors: S. A. Gharib, E. Nguyen, W. A. Altemeier, S. A. Shaffer, C. E. Doneanu, D. R. Goodlett, L. M. Schnapp
Journal: European Respiratory Journal (2009)

We hypothesised that comparing the protein mixture in bronchoalveolar lavage fluid (BALF) between humans and mice may lead to mechanistic insights into common and divergent pathways that evolved in each species. BALF from four humans and six mice was pooled separately and underwent identical shotgun proteomic analysis. Functional and network analysis was applied to identify overlapping and distinct pathways enriched in the BALF. Follow-up experiments using Western analysis in unpooled BALF samples were performed. We identified 91 unique proteins in human and 117 unique proteins in mouse BALF samples. Functional analysis of the proteins revealed conservation of several key processes between the species, including defence response. Oxidative stress response, however, was selectively enriched only in mouse BALF. Differences in the expression of peroxiredoxin-1, a key member of the defence pathway against oxidative injury, were confirmed between normal human and mouse BALF and in models of lung injury. A computational proteomics approach of mouse and human BALF confirms the conservation of immune and defence-mediated pathways while highlighting differences in response to oxidative stress. These observations suggest that the use of mice models to study human lung disorders should be undertaken with an appreciation of interspecies variability.
REGULATION OF MILK LIPID SECRETION AND COMPOSITION
Authors: Margaret C. Neville, Mary Frances Picciano
Journal: Annual Review of Nutrition (1997)

▪ Abstract Triacylglycerols make up 98% of the lipid content of milk, ranging in different species from 0 to 50% of the total milk volume. The fatty aid composition of the triacylglycerols depends on the species, the dietary fatty acid composition, and the carbohydrate-to-lipid ratio of the diet. The rate of lipid synthesis in the lactating mammary gland depends on the stage of mammary development and is decreased by fasting and starvation in ruminants and rodents but not in species that fast during lactation, such as seals and hibernating bears. Regulatory agents include insulin, prolactin, and non-esterified fatty acids. Dietary trans fatty acids may depress milk lipid synthesis under certain conditions. Evidence is presented that fatty acids may play a major regulatory role in acute changes in de novo mammary fatty acid synthesis, acting primarily on the activity of acetyl coenzyme A carboxylase.
GSK paid smaller companies to delay generic versions of paroxetine, says fair trade body
Authors: C. Dyer
Journal: BMJ (2013)

The UK Office of Fair Trading (OFT) has accused GlaxoSmithKline of breaching competition law and abusing its dominant market in the supply of an antidepressant.

The competition watchdog said that it would investigate a series of deals the United Kingdom’s biggest drug maker made between 2001 and 2004 with three smaller companies that wanted to market cheaper generic versions of GSK’s blockbuster drug paroxetine (which it markets as Seroxat).

The OFT alleges that GSK accused the generic manufacturers of infringeing its patents and, to settle the disputes, struck so called “pay for delay” deals, in …
The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm
Authors: Maarten J. Suttorp, J.Herre Kingma, Emile R. Jessurun, Loraine Lie-A-Huen, Norbert M. Van Hemel, Kong I. Lie
Journal: Journal of the American College of Cardiology (1990)
The Prognostic Role of a Gene Signature from Tumorigenic Breast-Cancer Cells
Authors: Rui Liu, Xinhao Wang, Grace Y. Chen, Piero Dalerba, Austin Gurney, Timothy Hoey, Gavin Sherlock, John Lewicki, Kerby Shedden, Michael F. Clarke
Journal: New England Journal of Medicine (2007)

Breast cancers contain a minority population of cancer cells characterized by CD44 expression but low or undetectable levels of CD24 (CD44+CD24-/low) that have higher tumorigenic capacity than other subtypes of cancer cells.We compared the gene-expression profile of CD44+CD24-/low tumorigenic breast-cancer cells with that of normal breast epithelium. Differentially expressed genes were used to generate a 186-gene "invasiveness" gene signature (IGS), which was evaluated for its association with overall survival and metastasis-free survival in patients with breast cancer or other types of cancer.There was a significant association between the IGS and both overall and metastasis-free survival (P<0.001, for both) in patients with breast cancer, which was independent of established clinical and pathological variables. When combined with the prognostic criteria of the National Institutes of Health, the IGS was used to stratify patients with high-risk early breast cancer into prognostic categories (good or poor); among patients with a good prognosis, the 10-year rate of metastasis-free survival was 81%, and among those with a poor prognosis, it was 57%. The IGS was also associated with the prognosis in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01). The prognostic power of the IGS was increased when combined with the wound-response (WR) signature.The IGS is strongly associated with metastasis-free survival and overall survival for four different types of tumors. This genetic signature of tumorigenic breast-cancer cells was even more strongly associated with clinical outcomes when combined with the WR signature in breast cancer.
Advertising in Medical Journals: Should Current Practices Change?
Authors: Adriane Fugh-Berman, Karen Alladin, Jarva Chow
Journal: PLoS Medicine (2006)

eer-reviewed medical journals are generally considered to be a source of unbiased and reliable information about drugs.But at the same time, most medical journals contain advertisements, almost all of which are for drugs, and which are, by their very nature, biased toward promoting sales of that drug.In this article, we address the purpose and effects of journal advertising, the possible reasons for pharmaceutical product domination of advertising pages, and the current policies and practices of representative journals.We also make recommendations for change. Advertising Drugs to Doctors: Scale and ImpactThe Policy Forum allows health policy makers around the world to discuss challenges and opportunities for improving health care in their societies.
Patterns of temperature adaptation in proteins from Methanococcus and Bacillus
Authors: J. H. McDonald, A. M. Grasso, L. K. Rejto
Journal: Molecular Biology and Evolution (1999)

It has long been known that amino acid substitutions in proteins of organisms living at moderate and high temperatures (mesophiles and thermophiles, respectively) are not all symmetrical; for example, more aligned sites have lysine in mesophiles and arginine in thermophiles than have the opposite pattern. This is generally taken to indicate that certain amino acids are favored over others by selection at different temperatures. Previous comparisons of protein sequences from mesophiles and thermophiles have used relatively small numbers of sequences from a diverse array of species, meaning that only the most common amino acid substitutions could be examined and any taxon-specific patterns would be obscured. Here, we compare a large number of proteins between mesophiles and thermophiles in the archaeal genus Methanococcus and the bacterial genus Bacillus. Each genus exhibits dramatically asymmetrical substitution patterns for many pairs of amino acids. There are several pairs of amino acids for which one amino acid is favored in thermophilic Bacillus and the other is favored in thermophilic Methanococcus; this appears to result from the higher G + C content of the DNA of thermophilic Bacillus, a complication not seen in Methanococcus.
Childhood Central Nervous System Viral Infections and Adult Schizophrenia
Authors: Jaana Suvisaari, Nicolas Mautemps, Jari Haukka, Tapani Hovi, Jouko Lönnqvist
Journal: American Journal of Psychiatry (2003)

An earlier Finnish cohort study suggested that childhood viral CNS infections are associated with a fivefold increased odds of developing schizophrenia in adulthood. The authors sought to replicate this finding.From the archives of the Department of Virology of the National Public Health Institute in Finland, 320 individuals born between 1960 and 1976 who had suffered virologically confirmed CNS infections before their 15th birthdays were identified. Of the infections, 202 had been caused by enteroviruses. The sample was followed up in the 1969-2000 records of the National Hospital Discharge Register of Finland to identify all cases of schizophrenia that emerged.The cumulative incidence of schizophrenia was 0.94% in the whole sample and 0.99% among individuals who had suffered enteroviral infections. These rates are comparable to that found in the general population.Childhood viral CNS infections were not associated with increased risk of schizophrenia.
Immunoglobulin kappa chain receptor editing in systemic lupus erythematosus.
Authors: T Dörner, S J Foster, N L Farner, P E Lipsky
Journal: Journal of Clinical Investigation (1998)

To determine whether receptor editing of Vkappa genes was involved in the pathogenesis of systemic lupus erythematosus (SLE), the usage of Vkappa and Jkappa gene elements from individual peripheral CD19(+) B cells obtained from a patient with untreated SLE was examined. No differences in the Vkappa and Jkappa gene usage in the nonproductive gene repertoire of this SLE patient were noted compared with the distribution of genes found in normal adults. However, an increased usage of Jkappa5 segments, and a significant overrepresentation of the Vkappa1 and Vkappa4 families, especially the L15, O14/O4, and B3 genes characterized the productive Vkappa gene repertoire of the SLE patient. Furthermore, Jkappa5-containing Vkappa gene rearrangements in the productive but not the nonproductive repertoire manifested significantly fewer mutations compared with Vkappa genes recombined with Jkappa1-4. These data are consistent with the conclusion that receptor editing of Vkappa is much more apparent in this SLE patient than in normals and suggest that a deficiency in this means to counteract the emergence of autoimmunity is not an essential feature of SLE.
Repeat-Enriched Proteins Are Related to Host Cell Invasion and Immune Evasion in Parasitic Protozoa
Authors: T.A.O. Mendes, F.P. Lobo, T.S. Rodrigues, G.F. Rodrigues-Luiz, W.D. daRocha, R.T. Fujiwara, S.M.R. Teixeira, D.C. Bartholomeu
Journal: Molecular Biology and Evolution (2013)

Proteins containing repetitive amino acid domains are widespread in all life forms. In parasitic organisms, proteins containing repeats play important roles such as cell adhesion and invasion and immune evasion. Therefore, extracellular and intracellular parasites are expected to be under different selective pressures regarding the repetitive content in their genomes. Here, we investigated whether there is a bias in the repetitive content found in the predicted proteomes of 6 exclusively extracellular and 17 obligate intracellular protozoan parasites, as well as 4 free-living protists. We also attempted to correlate the results with the distinct ecological niches they occupy and with distinct protein functions. We found that intracellular parasites have higher repetitive content in their proteomes than do extracellular parasites and free-living protists. In intracellular parasites, these repetitive proteins are located mainly at the parasite surface or are secreted and are enriched in amino acids known to be part of N- and O-glycosylation sites. Furthermore, in intracellular parasites, the developmental stages that are able to invade host cells express a higher proportion of proteins with perfect repeats relative to other life cycle stages, and these proteins have molecular functions associated with cell invasion. In contrast, in extracellular parasites, degenerate repetitive motifs are enriched in proteins that are likely to play roles in evading host immune response. Altogether, our results support the hypothesis that both the ability to invade host cells and to escape the host immune response may have shaped the expansion and maintenance of perfect and degenerate repeats in the genomes of intra- and extracellular parasites.
THE EFFECT OF ACUTE HYPOVOLEMIA ON THE RELEASE OF “ALDOSTERONE” AND ON THE RENAL EXCRETION OF SODIUM1
Authors: Daniel Fine, Leonard E. Meiselas, Theresa Auerbach
Journal: Journal of Clinical Investigation (1958)

Automatic control of the volume of the body fluids, involving adjustment of the renal excretion of electrolytes and water, has been the subject of much recent study. Accumulating evidence suggests that a variety of functions of the extracellular fluid volume are significant determinants of the renal excretion of sodium (2). Some investigators have emphasized the role of effective blood volume (or a related parameter) as such a function (3-6), but the precise stimuli involved and the mode of their transmission to the kidney remain incompletely understood.
Inducible costimulator (ICOS) blockade inhibits accumulation of polyfunctional T helper 1/T helper 17 cells and mitigates autoimmune arthritis
Authors: O. Frey, J. Meisel, A. Hutloff, K. Bonhagen, L. Bruns, R. A. Kroczek, L. Morawietz, T. Kamradt
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> Inducible costimulator (ICOS) and its ligand (ICOSL) regulate T and B cell responses. Glucose-6-phosphate isomerase (G6PI)-induced arthritis requires T and B lymphocytes. It was hypothesised that blocking ICOS/ICOSL interactions ameliorates G6PI-induced arthritis and reduces G6PI-specific B and T lymphocyte responses. <h3>Methods</h3> DBA/1 mice were injected with a blocking, non-depleting anti-ICOSL monoclonal antibodies (mAbs) during the induction or effector phase of G6PI-induced arthritis. G6PI-specific antibody responses were measured by ELISA. G6PI-specific T helper (Th) cell responses were assayed by polychromatic flow cytometry. <h3>Results</h3> Transient blockade of ICOS/ICOSL interactions profoundly reduced the severity of G6PI-induced arthritis. ELISA and proliferation assays showed no clear ex vivo correlates of protection. Polychromatic flow cytometry revealed two major findings: the absolute number of G6PI-specific Th cells was markedly diminished in secondary lymphatic organs from mice with blocked ICOS/ICOSL interactions. Within the pool of G6PI-specific Th cells the frequency of interleukin 17 (IL17), interferon γ or tumour necrosis factor α producers or polyfunctional Th cells (expressing two or more of these cytokines) was higher in treated than in control mice. <h3>Conclusions</h3> ICOS costimulation is not mandatory for the differentiation of Th1 or Th17 cells. Instead, the lack of ICOS costimulation results in reduced survival of G6PI-specific Th cells irrespective of their functional differentiation. This study demonstrates that a thorough examination of the quantity and the quality of antigen-specific immune responses is useful to determine ex vivo correlates of efficacy for immunomodulating treatments.
Novel insight from transgenic mice into thyroid hormone resistance and the regulation of thyrotropin
Authors: E. Dale Abel, Helen C. Kaulbach, Angel Campos-Barros, Rexford S. Ahima, Mary-Ellen Boers, Koshi Hashimoto, Douglas Forrest, Fredric E. Wondisford
Journal: Journal of Clinical Investigation (1999)

Patients with resistance to thyroid hormone (RTH) exhibit elevated thyroid hormone levels and inappropriate thyrotropin (thyroid-stimulating hormone, or TSH) production. The molecular basis of this disorder resides in the dominant inhibition of endogenous thyroid hormone receptors (TRs) by a mutant receptor. To determine the relative contributions of pituitary versus hypothalamic resistance to the dysregulated production of thyroid hormone in these patients, we developed a transgenic mouse model with pituitary-specific expression of a mutant TR (Δ337T). The equivalent mutation in humans is associated with severe generalized RTH. Transgenic mice developed profound pituitary resistance to thyroid hormone, as demonstrated by markedly elevated baseline and non–triodothyronine (T3)-suppressible serum TSH and pituitary TSH-β mRNA. Serum thyroxine (T4) levels were only marginally elevated in transgenic mice and thyrotropin-releasing hormone (TRH) gene expression in the paraventricular hypothalamus was downregulated. After TRH administration, T4 concentrations increased markedly in transgenic, but not in wild-type mice. Transgenic mice rendered hypothyroid exhibited a TSH response that was only 30% of the response observed in wild-type animals. These findings indicate that pituitary expression of this mutant TR impairs both T3-mediated suppression and T3-independent activation of TSH production in vivo. The discordance between basal TSH and T4 levels and the reversal with TRH administration demonstrates that resistance at the level of both the thyrotroph and the hypothalamic TRH neurons are required to elevate thyroid hormone levels in patients with RTH.
Law Enforcement Interviews of Hospital Patients&lt;SUBTITLE&gt;A Conundrum for Clinicians&lt;/SUBTITLE&gt;
Authors: Paul M Jones, Paul S Appelbaum, David M Siegel
Journal: JAMA (2006)

LAW ENFORCEMENT INTERVIEWS OF HOSPITAL PAtients are a common but underrecognized phenomenon in US medicine. Daily in emergency departments and inpatient trauma services, and sporadically in other departments, police officers request permission to interview patients who may have experienced, witnessed, or perpetrated crimes ranging from motor vehicle crashes to homicides. These interviews are often time sensitive, and how they are conducted may have clinical consequences, alter legal outcomes for patients and physicians, and affect public safety. Yet law enforcement access to patients is not explicitly regulated by federal or state law, relevant professional guidelines are so limited as to be negligible, and medical literature on the subject is minimal. Decision making by both clinicians and police is consequently unstructured, ad hoc, and potentially susceptible to adverse outcomes that might be preventable with appropriate guidance. In this Commentary, we examine the phenomenon and risks of police interviews in hospitals, review limits to available guidance, and explore relevant ethical concerns. We conclude by suggesting 5 principles to help guide physicians responding to police interview requests.
Resolved
Authors: Michael Zeisberg, Jeremy S Duffield
Journal: Journal of the American Society of Nephrology (2010)

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Is atopy a risk factor for the use of contact lenses?
Authors: O. Kari, T. Haahtela
Journal: Allergy (1992)

We studied the tolerance of soft contact lenses (CL) in 24 atopic (16 with hay fever) and 52 non-atopic subjects with a mean age of 20 years. They were examined when they first came to an ophthalmologist to have CL and re-examined after an average of 1.7 years. All subjects were allowed to use CL throughout the year, including the pollen season. Of the 76 subjects, 31 (41%) reported some kind of eye symptoms during the use of CL. Six subjects (8%) had stopped using CL because of symptoms. Altogether, in 29/76 subjects (38%) some objective sign was detected in the examination, confirming the subjective symptoms (conjunctivitis 16, keratoconjunctivitis 8, increased limbal blood vessels 4, and eczema palpebrae 1). Fourteen of the 24 atopics (58%) had experienced symptoms compared with 17 of the 52 non-atopics (33%) (p = 0.034). Eleven atopics had seasonal eye symptoms, and eight of them (73%) had problems with CL use. Eosinophils and neutrophils found in the conjunctival scrapings at the first examination appeared to predict poor CL tolerance when the occurrence of symptoms in different groups was first compared by bivariate analysis. The risk factors that could predict poor CL tolerance were also evaluated, with logistic regression analysis controlling potential confounders. History of an atopic condition increased 5-fold the risk of experiencing various external eye symptoms during the use of CL. We conclude that seasonal atopic allergy is a especially risk factor for wearing soft contact lenses, and their use should be restricted during the season.
Angiotensin II Type 1A Receptor Knockout Mice Display Less Left Ventricular Remodeling and Improved Survival After Myocardial Infarction
Authors: Koichiro Harada, Takeshi Sugaya, Kazuo Murakami, Yoshio Yazaki, Issei Komuro
Journal: Circulation (1999)

Angiotensin II (Ang II) has been implicated in ventricular remodeling after myocardial infarction (MI), which is an important determinant for prognosis after MI. The aim of this study was to determine whether Ang II type 1A receptor (AT(1A))-mediated Ang II signals are critically involved in the mortality and LV remodeling after MI.We examined survival, cardiac geometry and function, cardiac fibrosis, and gene expression of AT(1A) knockout (KO) mice and wild-type (WT) mice at 1 and 4 weeks after large MI. The survival rate was higher in KO mice than in WT mice at 4 weeks after MI. All WT survivors showed severe heart failure, detected by marked increases in both RV weight and lung weight. LV remodeling, such as the development of LV dilatation, LV dysfunction, and cardiac fibrosis at the noninfarcted area, were comparable in both kinds of mice at 1 week after MI. At 4 weeks after MI, however, WT mice showed more marked remodeling than KO mice. mRNA levels of AT(1) at the noninfarcted area were increased from 1 to 4 weeks after MI only in WT mice, whereas levels of AT(2) were not changed by MI in either kind of mouse. Accompanied by the development of geometric and structural remodeling, expression of fetal-type genes, collagen, and transforming growth factor-beta(1) genes were upregulated and sustained in the noninfarcted area of WT hearts. In contrast, they were rapidly downregulated to basal levels at 4 weeks after MI in that of KO hearts.These results indicate that AT(1A) signals play a pivotal role in the progression of LV remodeling after MI, resulting in overt heart failure.