tbuckley/cabot-search huggingface dataset:
Phylogenetic Analyses Uncover a Novel Clade of Transferrin in Nonmammalian Vertebrates
Authors: Hirzahida Mohd-Padil, Adura Mohd-Adnan, Toni Gabaldón
Journal: Molecular Biology and Evolution (2012)

Transferrin is a protein super-family involved in iron transport, a central process in cellular homeostasis. Throughout the evolution of vertebrates, transferrin members have diversified into distinct subfamilies including serotransferrin, ovotransferrin, lactoferrin, melanotransferrin, the inhibitor of carbonic anhydrase, pacifastin, and the major yolk protein in sea urchin. Previous phylogenetic analyses have established the branching order of the diverse transferrin subfamilies but were mostly focused on the transferrin repertoire present in mammals. Here, we conduct a comprehensive phylogenetic analysis of transferrin protein sequences in sequenced vertebrates, placing a special focus on the less-studied nonmammalian vertebrates. Our analyses uncover a novel transferrin clade present across fish, sauropsid, and amphibian genomes but strikingly absent from mammals. Our reconstructed scenario implies that this novel class emerged through a duplication event at the vertebrate ancestor, and that it was subsequently lost in the lineage leading to mammals. We detect footprints of accelerated evolution following the duplication event, which suggest positive selection and early functional divergence of this novel clade. Interestingly, the loss of this novel class of transferrin in mammals coincided with the divergence by duplication of lactoferrin and serotransferrin in this lineage. Altogether, our results provide novel insights on the evolution of iron-binding proteins in the various vertebrate groups.
The Dormancy Dilemma: Quiescence versus Balanced Proliferation
Authors: Alan Wells, Linda Griffith, Jakob Z. Wells, Donald P. Taylor
Journal: Cancer Research (2013)

Metastatic dissemination with subsequent clinical outgrowth leads to the greatest part of morbidity and mortality from most solid tumors. Even more daunting is that many of these metastatic deposits silently lie undetected, recurring years to decades after primary tumor extirpation by surgery or radiation (termed metastatic dormancy). As primary tumors are frequently curable, a critical focus now turns to preventing the lethal emergence from metastatic dormancy. Current carcinoma treatments include adjuvant therapy intended to kill the cryptic metastatic tumor cells. Because such standard therapies mainly kill cycling cells, this approach carries an implicit assumption that metastatic cells are in the mitogenic cycle. Thus, the pivotal question arises as to whether clinically occult micrometastases survive in a state of balanced proliferation and death, or whether these cells undergo at least long periods of quiescence marked by cell-cycle arrest. The treatment implications are thus obvious--if the carcinoma cells are cycling then therapies should target cycling cells, whereas if cells are quiescent then therapies should either maintain dormancy or be toxic to dormant cells. Because this distinction is paramount to rational therapeutic development and administration, we investigated whether quiescence or balanced proliferation is the most likely etiology underlying metastatic dormancy. We recently published a computer simulation study that determined that balanced proliferation is not the likely driving force and that quiescence most likely participates in metastatic dormancy. As such, a greater emphasis on developing diagnostics and therapeutics for quiescent carcinomas is needed.
Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes.
Authors: L A Casciola-Rosen, G Anhalt, A Rosen
Journal: The Journal of Experimental Medicine (1994)

Systemic lupus erythematosus is a multisystem autoimmune disease in which the autoantibody response targets a variety of autoantigens of diverse subcellular location. We show here that these autoantigens are clustered in two distinct populations of blebs at the surface of apoptotic cells. The population of smaller blebs contains fragmented endoplasmic reticulum (ER) and ribosomes, as well as the ribonucleoprotein, Ro. The larger blebs (apoptotic bodies) contain nucleosomal DNA, Ro, La, and the small nuclear ribonucleoproteins. These autoantigen clusters have in common their proximity to the ER and nuclear membranes, sites of increased generation of reactive oxygen species in apoptotic cells. Oxidative modification at these sites may be a mechanism that unites this diverse group of molecules together as autoantigens.
THE PATHOGENESIS OF EXPERIMENTAL DYSENTERY INTOXICATION
Authors: Abraham Penner, Samuel H. Klein
Journal: The Journal of Experimental Medicine (1952)

All analysis of the mechanisms involved in the pathogenesis of the visceral lesions produced by Shiga toxin in the dog has indicated that the structural changes are produced by a vascular mechanism which is under control of the sympathetic nervous system. Paralysis of the latter at the myoneural junction or in the ganglia by means of drugs served to prevent the tissue changes as well as the hyperglycemia and hemoconcentration characteristic of the sympathomimetic response. The observations indicated that the toxin acted via a mechanism located in the central nervous system. Further studies of the action of Shiga toxin by means of cerebral cross-circulation are reported here. In these the cerebral blood flow of one dog derived from the circulation of the trunk and limbs of another. Injection of the toxin into the femoral vein of this latter dog resulted in the appearance of visceral lesions, hemoconcentration, and hyperglycemia in the former whose brain only received blood containing the toxin. The resulting visceral changes were identical with those observed in the intact unanesthetized dog which had received the toxin directly. The observations indicate that, in dogs, Shiga toxin produces its characteristic visceral lesions via the central nervous system. Possible mechanisms are discussed.
PSYCHOTHERAPY IN CHILD SCHIZOPHRENIA
Authors: J. LOUISE DESPERT
Journal: American Journal of Psychiatry (1947)

Seven schizophrenic children, 6 boys and 1 girl, received ambulatory treatment, psychotherapy, over periods ranging from a few months to 2½ years, with varying degrees of success. Summaries of the 7 cases are presented, with emphasis on therapy and progress. On the whole, chances for relative recovery and adjustment seem to be greater than is the case with therapy in institutions.
Follow-up of children with obstructive sleep apnea syndrome treated with adenotonsillectomy
Authors: Filomena Ianniello, Danila D'Onofrio, Maria Chiara Paolino, Rosa Castaldo, Alceo Crescenzi, Alessandra Tabarrini, Silvia Miano, Marco Del Pozzo, Maria Pia Villa
Journal: European Respiratory Journal (2011)

Background:  Hypertrophy of adenotonsillar tissue is an undisputed contributor to the development of OSAS in otherwise healthy children. A multicenter retrospective study shows the surgery approach has a resolution rate of about 27%. So it will be important to identify children who will not resolve OSAS after adenotonsillectomy (AT) in order to plan an appropriate and integrated treatment for them.   Aim:  To evaluate the role of AT in the outcome of children with OSAS.   Methods:  Children affected by adenotonsillar hypertrophy, who underwent adenotonsillectomy for moderate-severe OSAS, were enrolled, from 2008 to 2009. All children underwent a complete clinical examination and overnight polysomnographic study before AT and after 12 months of follow-up.   Results:  We included 21 children (mean age 4.09±1.76; M/F 17/4), with a mean body mass index –BMI- of 15.86±2.4 kg/m 2 , with a mean apnea hyponea index (AHI) of 15.08±8.8 ev/hr. Twelve children (57.1%) had malocclusions. After one year, 13 children showed a complete resolution of disease (61.9%) (AHI 0.3±0.3 ev/hr), while 8 children (38.1%) had a residual disease (AHI 2.6±1.1 ev/hr). Children with a residual disease had a higher BMI at baseline (16.5±3.7kg/m 2  vs 15.4±1.1 kg/m 2 , p 2 =4.86, p 2 =0.24).   Conclusions:  Although AT is the gold standard in children with OSAS and adenotonsillar hypertrophy, treatment of malocclusions need to be added to achieve a complete resolution of the disease.
Erythropoietin Is Highly Elevated in Vitreous Fluid of Patients With Proliferative Diabetic Retinopathy
Authors: Yoshiya Katsura, Tadashi Okano, Kazuhisa Matsuno, Masahiro Osako, Masahiko Kure, Toshiya Watanabe, Yoshiki Iwaki, Masayuki Noritake, Hiroshi Kosano, Hideo Nishigori, Takeshi Matsuoka
Journal: Diabetes Care (2005)

Diabetic retinopathy is characterized by increased vascular permeability, ischemia, and neovascularization. Ischemia in the retina can induce neovascularization via induction of vascular endothelial growth factor (VEGF) expression by the transcription factor hypoxia-inducible factor-1 (1). Hypoxia is also the main stimulus for erythropoietin (EPO) gene expression. It has been reported that EPO may have not only erythropoietic (2) but also neuroprotective (3) and angiogenic (4) effects. EPO is expressed at a number of sites including kidney, liver, brain, uterus (5), and the adult mammalian retina, which also expresses EPO receptors (6). The aim of this study was to investigate whether EPO is elevated in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and whether vitreous EPO levels are related to systemic levels of EPO, anemia, or nephropathy.

Vitreous fluid samples were obtained from 59 PDR patients and 16 macular hole patients at the start of the vitrectomy procedure. Concentrations of EPO in vitreous fluid and serum samples were measured by an enzyme-linked immunosorbent assay for EPO (Toyobouseki, Osaka, Japan). Concentrations of VEGF were measured by an enzyme-linked immunosorbent assay for human VEGF (R & D Systems, Minneapolis, MN). Protein in vitreous fluid was determined using the method of Bradford (Bio-Rad, Hercules, CA). The Mann-Whitney U test was used to compare intravitreous concentrations of protein, VEGF, …
Imaging Studies after a First Febrile Urinary Tract Infection in Young Children
Authors: Alejandro Hoberman, Martin Charron, Robert W. Hickey, Marc Baskin, Diana H. Kearney, Ellen R. Wald
Journal: New England Journal of Medicine (2003)

Guidelines from the American Academy of Pediatrics recommend obtaining a voiding cystourethrogram and a renal ultrasonogram for young children after a first urinary tract infection; renal scanning with technetium-99m–labeled dimercaptosuccinic acid has also been endorsed by other authorities. We investigated whether imaging studies altered management or improved outcomes in young children with a first febrile urinary tract infection.
Changes in Brain Natriuretic Peptide Levels and Bioelectrical Impedance Measurements After Treatment With High-Dose Furosemide and Hypertonic Saline Solution Versus High-Dose Furosemide Alone in Refractory Congestive Heart Failure
Authors: Salvatore Paterna, Pietro Di Pasquale, Gaspare Parrinello, Ersilia Fornaciari, Francesca Di Gaudio, Sergio Fasullo, Marco Giammanco, Filippo M. Sarullo, Giuseppe Licata
Journal: Journal of the American College of Cardiology (2005)
The importance of calcium in interpretation of NaK-ATPase isoform function in the mouse heart
Authors: A Schwartz
Journal: Cardiovascular Research (2001)

We have recently emphasized an important role for intracellular calcium in changes that occur in the adrenergic system in cardiac hypertrophy and failure in the mouse heart [1,2]. For example, the blunting or loss of function of the β-adrenergic receptor signaling pathway that has been described for a number of mouse transgenic models can be restored to normal by “unloading” the heart of calcium [2]. It is well known that the isolated rat heart responds in a perfectly normal manner to a variety of pharmacological agents including digitalis and to physiological stimuli, but only when the perfusion media contains “low” calcium, ranging from 0.25 to 1.0 mM [3–7].

Less is known about the isolated mouse heart although most agree that the calcium requirements for pharmacological and physiological studies are the same as the rat [5].

In the case of the NaK-ATPase (NKA) three α isoforms have been described. The adult heart contains all three, the adult rat heart expresses α1 and α2and the adult guinea pig heart expresses only the α1. The subcellular distribution for these isoforms has been described [8]. In terms of characteristics, all three isoforms are quite similar in kinetics, affinities for the monovalent ions, Mg2+ and ATP. There are some differences described in isolated heart studies for the relative affinities of cardiac glycosides, but nothing, in our opinion, of such magnitude to have pharmacological or toxicological significance. For some years, there has been much discussion about different functions for these isoforms and conjecture about co-localization or not of specific isoforms with the Na/Ca exchange protein. The latter has bearing on a concept of a putative endogenous ouabain-like factor as well as assigning a specific role for one isoform to digitalis-induced positive inotropy and for another … 

*Corresponding author. Tel.: +1-513-5582-400; fax: +1-513-5581-778
Intermediate and Longer-Term Outcomes From a Prospective Active-Surveillance Program for Favorable-Risk Prostate Cancer
Authors: Jeffrey J. Tosoian, Mufaddal Mamawala, Jonathan I. Epstein, Patricia Landis, Sacha Wolf, Bruce J. Trock, H. Ballentine Carter
Journal: Journal of Clinical Oncology (2015)

To assess long-term outcomes of men with favorable-risk prostate cancer in a prospective, active-surveillance program.Curative intervention was recommended for disease reclassification to higher cancer grade or volume on prostate biopsy. Primary outcomes were overall, cancer-specific, and metastasis-free survival. Secondary outcomes were the cumulative incidence of reclassification and curative intervention. Factors associated with grade reclassification and curative intervention were evaluated in a Cox proportional hazards model.A total of 1,298 men (median age, 66 years) with a median follow-up of 5 years (range, 0.01 to 18.00 years) contributed 6,766 person-years of follow-up since 1995. Overall, cancer-specific, and metastasis-free survival rates were 93%, 99.9%, and 99.4%, respectively, at 10 years and 69%, 99.9%, and 99.4%, respectively, at 15 years. The cumulative incidence of grade reclassification was 26% at 10 years and was 31% at 15 years; cumulative incidence of curative intervention was 50% at 10 years and was 57% at 15 years. The median treatment-free survival was 8.5 years (range, 0.01 to 18 years). Factors associated with grade reclassification were older age (hazard ratio [HR], 1.03 for each additional year; 95% CI, 1.01 to 1.06), prostate-specific antigen density (HR, 1.21 per 0.1 unit increase; 95% CI, 1.12 to 1.46), and greater number of positive biopsy cores (HR, 1.47 for each additional positive core; 95% CI, 1.26 to 1.69). Factors associated with intervention were prostate-specific antigen density (HR, 1.38 per 0.1 unit increase; 95% CI, 1.22 to 1.56) and a greater number of positive biopsy cores (HR, 1.35 for one additional positive core; 95% CI, 1.19 to 1.53).Men with favorable-risk prostate cancer should be informed of the low likelihood of harm from their diagnosis and should be encouraged to consider surveillance rather than curative intervention.
Sex Differences in Structure and Expression of the Sex Chromosome Genes CHD1Z and CHD1W in Zebra Finches
Authors: Robert J. Agate, Meeryo Choe, Arthur P. Arnold
Journal: Molecular Biology and Evolution (2004)

Genes on the sex chromosomes are unique because of their sex-specific inheritance. One question is whether homologous gene pairs on the sex chromosomes, which have diverged in their sequence, have acquired different functions. We have analyzed the first homologous pair of genes (CHD1Z and CHD1W) discovered on the avian Z and W sex chromosomes of the zebra finch (Taeniopygia guttata) to examine whether functional differences may have evolved. Sequence analysis revealed that the two genes maintained a high degree of similarity especially within the C, H, and D domains, but outside of these regions larger differences were observed. Expression studies showed that CHD1W was unique to females and has the potential to produce a protein that CHD1Z does not. CHD1Z mRNA was expressed at a higher level in the male brain than in the female brain at various post-hatch ages. Reporter constructs containing the 5′ flanking regions of each gene showed they had the ability to drive reporter expression in primary cell cultures. The 5′ flanking region sequence of CHD1Z and CHD1W exhibited little homology, and differences in putative promoter elements were apparent. These differences between CHD1Z and CHD1W suggest that the two proteins may have diverged in their function.
Effects of patient education on compliance with basic treatment regimens and health in recent onset active rheumatoid arthritis
Authors: H. L M Brus, M. A F J van de Laar, E. Taal, J. J Rasker, O. Wiegman
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVES</h3> To determine the effects of patient education on compliance and on health in patients with active, recent onset rheumatoid arthritis (RA). <h3>METHODS</h3> A randomised, controlled, assessor blinded, one year trial. The experimental group followed an education programme. All patients started on sulphasalazine therapy. Compliance with sulphasalazine was measured by pill counting. Compliance rates with regimens of physical exercise, endurance activities, and energy conservation were measured by questionnaires. Compliance with prescriptions of joint protection was scored using a test for joint protection performance. Health was measured by a Disease Activity Score (function of erythrocyte sedimentation rate, Ritchie score, and number of swollen joints), C reactive protein, Dutch-AIMS scores, and M-HAQ scores, range of motion of shoulder, elbow, and knee joints. Parameters were scored at baseline and after three, six, and 12 months. <h3>RESULTS</h3> Sixty of 65 patients gave informed consent, five of them withdrew from follow up. Compliance with sulphasalazine exceeded 80% with no differences between groups. Compliance with physical exercise (at three months), energy conservation (at three and at 12 months), and joint protection (at three months) improved significantly more in the experimental group. The improvements of health were not different in the groups. <h3>CONCLUSION</h3> Compliance with sulphasalazine among patients with active, recent onset RA is high, whether formal patient education is followed or not. Compliance with physical exercise, energy conservation, and joint protection was increased by patient education. Formal patient education did not improve health status.
Lung fibroblasts from patients with emphysema show a reduced proliferation rate in culture
Authors: O. Holz, I. Zühlke, E. Jaksztat, K.C. Müller, L. Welker, M. Nakashima, K.D. Diemel, D. Branscheid, H. Magnussen, R.A. Jörres
Journal: European Respiratory Journal (2004)

Emphysema is characterised by a loss of alveolar structure, as reflected in elastic recoil and gas exchange. As fibroblasts play a key role in the maintenance of structure, the current authors hypothesised that their proliferation might be constitutively impaired in lung emphysema. Using explant cultures, lung fibroblasts were obtained from resected lungs of 10 patients with emphysema (median forced expiratory volume in one second (FEV1) 40% predicted) and 10 control patients (FEV1, 95% pred). The doubling time (DT) was measured over 4 days under standard conditions (10% foetal calf serum) prior and after cryopreservation. Additionally, in seven samples per group the total population doubling level (PDL) was determined. In emphysema, mean+/-sem DT was 33.6+/-2.8 h compared with 24.8+/-1.4 h in controls. The differences in DT were preserved after cryopreservation. Groups also differed in the initial slope of the PDL plot during long-term culture (up to 35 days). However, the median (range) maximum PDL did not differ significantly between groups (13.8 (7.4-22.6) versus 20.2 (11.2-25.5)). The current authors, therefore, suggest that the reduced proliferation rate in vitro of lung fibroblasts from patients with emphysema reflects a persistent, intrinsic failure of cellular replacement and maintenance in this disease, possibly in relation to pre-term aging.
Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics
Authors: Mary Jeanne Kreek, Orna Levran, Brian Reed, Stefan D. Schlussman, Yan Zhou, Eduardo R. Butelman
Journal: Journal of Clinical Investigation (2012)

Addictive diseases, including addiction to heroin, prescription opioids, or cocaine, pose massive personal and public health costs. Addictions are chronic relapsing diseases of the brain caused by drug-induced direct effects and persisting neuroadaptations at the epigenetic, mRNA, neuropeptide, neurotransmitter, or protein levels. These neuroadaptations, which can be specific to drug type, and their resultant behaviors are modified by various internal and external environmental factors, including stress responsivity, addict mindset, and social setting. Specific gene variants, including variants encoding pharmacological target proteins or genes mediating neuroadaptations, also modify vulnerability at particular stages of addiction. Greater understanding of these interacting factors through laboratory-based and translational studies have the potential to optimize early interventions for the therapy of chronic addictive diseases and to reduce the burden of relapse. Here, we review the molecular neurobiology and genetics of opiate addiction, including heroin and prescription opioids, and cocaine addiction.
Respiratory tract inflammation during the induction of chronic bronchitis in rats: role of C‐fibres
Authors: N.C. Long, J. Abraham, L. Kobzik, E.A. Weller, G.G. Krishna Murthy, S.A. Shore
Journal: European Respiratory Journal (1999)

The hypothesis that chronic stimulation of C-fibres by inhaled irritants contributes to the inflammatory changes that occur during the development of chronic bronchitis was tested. The effect of neonatal capsaicin pretreatment on the development of respiratory tract inflammation was examined in a rat model of chronic bronchitis induced by SO2 exposure. Adult capsaicin- and vehicle-treated rats were exposed to SO2 (250 parts per million (ppm) 5 h x day(-1)) for one day, 2 weeks or 4 weeks. Nasal (NL), airway (AL) and bronchoalveolar (BAL) lavages were performed and the number and types of cells in the lavage fluids measured. SO2-induced changes in ventilation were also measured on day 1 of SO2 exposure and in the 3rd and 5th week of exposure. In the vehicle-treated rats, neutrophils became elevated in NL after just one day of SO2 exposure, in AL after 2 weeks, and in the BAL after 4 weeks. In comparison to vehicle animals, more neutrophils were recovered in the AL of capsaicin-treated rats after one day of SO2 (p=0.012), and in the BAL after 2 or 4 weeks (p=0.004 and p=0.01, respectively). On day 1, SO2 caused a transient increase in tidal volume and a sustained decrease in frequency that was not different in capsaicin- and vehicle-treated rats. With continued exposure, these ventilatory responses to SO2 were attenuated in both groups of rats. These data support the hypothesis that the presence of C-fibres limits or delays the inflammation that occurs during the development of chronic bronchitis induced by SO2 exposure. The protective effect of C-fibres is not the result of ventilatory responses to stimulation of these afferents.
The waiting game: bridging to paediatric heart transplantation
Authors: Allan P Goldman, Jane Cassidy, Marc de Leval, Simon Haynes, Katherine Brown, Pauline Whitmore, Gordon Cohen, Victor Tsang, Martin Elliott, Anne Davison, Leslie Hamilton, David Bolton, Jo Wray, Asif Hasan, Rosemary Radley-Smith, Duncan Macrae, Jon Smith
Journal: The Lancet (2003)