tbuckley/cabot-search huggingface dataset:
Identification and functional significance of troponin I isoforms in neonatal rat heart myofibrils.
Authors: A F Martin, K Ball, L Z Gao, P Kumar, R J Solaro
Journal: Circulation Research (1991)

We investigated the mechanism(s) responsible for differences in the effects of acidic pH on Ca2+ activation of the activity of adult and neonatal rat heart myofilaments. Studies on preparations of myofilaments reconstituted with adult troponin-tropomyosin (Tn-Tm) and either adult or neonatal thick filaments indicated that the difference in effect of acidic pH is related to differences in Tn-Tm and not other myofilament proteins. Immunoblotting analysis showed that development of the rat heart myofibrils is associated with isoform switching from slow skeletal TnI to cardiac TnI and from a slow mobility isoform of TnT (TnT1) to a faster Mr isoform (TnT2. Expression of slow skeletal TnI was associated with a relative insensitivity of myofilament Ca2+ activation to deactivation by acidic pH. Moreover, the effect of acidic pH on Ca2+ activation of ATPase activity of soleus myofibrils, which contain cardiac TnC and slow skeletal TnI, was essentially the same as the effect of acidic pH on rat cardiac myofibrils in the early neonatal period. Neonatal myofilaments also contained a relative abundance of a set of polypeptides copurifying with the thin filaments. We have identified these proteins as histones. The relative amount of histones among a variety of preparations from different species was not correlated with the pH sensitivity of myofibrillar Ca2+ activation. Shifts in TnT isoforms among these species were also not correlated with an altered response to acidic pH. Our data provide evidence in support of the hypothesis that the relative insensitivity of neonatal myofilament activity to acidic pH is due to the presence of slow skeletal TnI in the thin-filament regulatory complex.
DNA methylation controls the responsiveness of hepatoma cells to leukemia inhibitory factor
Authors: Frédéric Blanchard, Erin Tracy, Joseph Smith, Souvik Chattopadhyay, Yanping Wang, William A. Held, Heinz Baumann
Journal: Hepatology (2003)

The related members of the interleukin 6 (IL–6) family of cytokines, IL–6, leukemia inhibitory factor (LIF), and oncostatin M, act as major inflammatory mediators and induce the hepatic acute phase reaction. Normal parenchymal liver cells express the receptors for these cytokines, and these receptors activate, to a comparable level, the intracellular signaling through signal transducer and activator of transcription (STAT) proteins and extracellular–regulated kinase (ERK). In contrast, hepatoma cell lines show attenuated responsiveness to some of these cytokines that is correlated with lower expression of the corresponding ligand–binding receptor subunits. This study tests the hypothesis that the reduced expression of LIF receptor (LIFR) observed in hepatoma cells is mediated by altered DNA methylation. H–35 rat hepatoma cells that have a greatly reduced LIF responsiveness were treated with 5–aza–2′–deoxycytidine, an inhibitor of DNA methyltransferase. Surviving and proliferating cells showed reestablished expression of LIFR protein and function. Restriction landmark genomic scanning (RLGS) demonstrated genome–wide drug–induced alterations in DNA methylation status, with striking similarities in the demethylation pattern among independently derived clonal lines. Upon extended growth in the absence of 5–aza–2′–deoxycytidine, the cells exhibit partial reversion to pretreatment patterns. Demethylation and remethylation of the CpG island within the LIFR promoter that is active in normal liver cells correlate with increased and decreased usage of this promoter in H–35 cells. In conclusion, these results indicate that transformed liver cells frequently undergo epigenetic alterations that suppress LIFR gene expression and modify the responsiveness to this IL–6 type cytokine.
Recurrent pleural effusion, protein-losing enteropathy, malabsorption, and mosaic warts associated with generalized lymphatic hypoplasia
Authors: J. D. Ross, K. D. G. Reid, V. P. Ambujakshan, J. D. Kinloch, W. Sircus
Journal: Thorax (1971)

A patient is described who presented with pleural effusions, asymmetrical oedema of the face and limbs, and numerous warts of the hands and feet. He was shown to have vitamin B<sub>12</sub> malabsorption, steatorrhoea, and a protein-losing enteropathy. Lymphography showed asymmetrical lymphatic hypoplasia. Jejunal biopsy showed intestinal lymphangiectasia. The hypoproteinaemia responded well to a low-fat, high-protein diet. Corticosteroids at first appeared to speed resolution of the pleural effusion but had only a limited effect. The effusion was attributed to infections injuring a lymphatic system already impaired.
Untreated Initial Psychosis: Its Relation to Quality of Life and Symptom Remission in First-Episode Schizophrenia
Authors: Beng-Choon Ho, Nancy C. Andreasen, Michael Flaum, Peg Nopoulos, Del Miller
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Previous studies have suggested that there may be an association between longer duration of untreated psychosis and poor outcome in schizophrenia. These studies have been interpreted as providing evidence that untreated psychosis may constitute an "active morbid process" that is "toxic" to the brain. If untreated psychosis is neurotoxic, this would form a strong basis for early intervention in schizophrenia. METHOD: Seventy-four neuroleptic-naive patients with DSM-IV schizophrenia were evaluated 6 months after their first inpatient hospitalization. The authors examined the relationship between untreated initial psychosis duration (measured from onset of first symptom as well as from onset of full positive syndrome) and quality of life, symptom severity, and time to remission of positive symptoms. RESULTS: Earlier age at illness onset was associated with longer duration of untreated prodromal psychotic symptoms. There were no significant gender differences in duration of untreated initial psychosis, nor were there any significant associations between untreated initial psychosis duration and premorbid functioning. After controlling for the effects of age at onset, the duration of untreated initial psychosis did not significantly impair subsequent quality of life, symptom severity, or remission of positive symptoms. CONCLUSIONS: Duration of untreated initial psychosis was not prognostic of poor outcome early in the course of schizophrenia. Biological measures of neurotoxicity are needed to examine the "toxic psychosis" hypothesis more directly.
Uncovering a connection between physiological stress and therapeutic resistance in tumor cells
Authors: Jason W Eng, Chelsey Reed, Kathleen M Kokolus, Rose Pitoniak, Bonnie L Hylander, Elizabeth A Repasky
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Environmental stress, including that caused by ambient temperature, significantly impacts many biological processes. Under conditions of cold stress, the sympathetic nervous system and a subpopulation of alternatively activated macrophages produce norepinephrine to maintain
Expression of the nuclear factor-κB inhibitor A20 is altered in the cystic fibrosis epithelium
Authors: Catriona Kelly, Mark T. Williams, Kathryn Mitchell, J. Stuart Elborn, Madeleine Ennis, Bettina C. Schock
Journal: European Respiratory Journal (2012)

A20 is a lipopolysaccharide (LPS)-inducible, cytoplasmic zinc finger protein, which inhibits Toll-like receptor-activated nuclear factor (NF)-κB signalling by deubiquitinating tumour necrosis factor receptor-associated factor (TRAF)-6. The action of A20 is facilitated by complex formation with ring finger protein (RNF)-11, Itch and TAX-1 binding protein-1 (TAX1BP1). This study investigated whether the expression of A20 is altered in the chronically inflamed cystic fibrosis (CF) airway epithelium. Nasal epithelial cells from CF patients (F508del homozygous), non-CF controls and immortalised epithelial cells (16HBE14o- and CFBE41o-) were stimulated with LPS. Cytoplasmic expression of A20 and expression of NF-κB subunits were analysed. Formation of the A20 ubiquitin editing complex was also investigated. In CFBE41o-, peak LPS-induced A20 expression was delayed compared with 16HBE14o- and fell significantly below basal levels 12–24 h after LPS stimulation. This was confirmed in primary CF airway cells. Additionally, a significant inverse relationship between A20 and p65 expression was observed. Inhibitor studies showed that A20 does not undergo proteasomal degradation in CFBE41o-. A20 interacted with TAX1BP1, RNF11 and TRAF6 in 16HBE14o- cells, but these interactions were not observed in CFBE41o-. The expression of A20 is significantly altered in CF, and important interactions with complex members and target proteins are lost, which may contribute to the state of chronic NF-κB-driven inflammation.
Assignment of orthologous relationships among mammalian alpha-globin genes by examining flanking regions reveals a rapid rate of evolution.
Authors: R C Hardison, R E Gelinas
Journal: Molecular Biology and Evolution (1986)

In order to study the relationships among mammalian alpha-globin genes, we have determined the sequence of the 3' flanking region of the human alpha 1 globin gene and have made pairwise comparisons between sequenced alpha-globin genes. The flanking regions were examined in detail because sequence matches in these regions could be interpreted with the least complication from the gene duplications and conversions that have occurred frequently in mammalian alpha-like globin gene clusters. We found good matches between the flanking regions of human alpha 1 and rabbit alpha 1, human psi alpha 1 and goat I alpha, human alpha 2 and goat II alpha, and horse alpha 1 and goat II alpha. These matches were used to align the alpha-globin genes in gene clusters from different mammals. This alignment shows that genes at equivalent positions in the gene clusters of different mammals can be functional or nonfunctional, depending on whether they corrected against a functional alpha-globin gene in recent evolutionary history. The number of alpha-globin genes (including pseudogenes) appears to differ among species, although highly divergent pseudogenes may not have been detected in all species examined. Although matching sequences could be found in interspecies comparisons of the flanking regions of alpha-globin genes, these matches are not as extensive as those found in the flanking regions of mammalian beta-like globin genes. This observation suggests that the noncoding sequences in the mammalian alpha-globin gene clusters are evolving at a faster rate than those in the beta-like globin gene clusters. The proposed faster rate of evolution fits with the poor conservation of the genetic linkage map around alpha-globin gene clusters when compared to that of the beta-like globin gene clusters. Analysis of the 3' flanking regions of alpha-globin genes has revealed a conserved sequence approximately 100-150 bp 3' to the polyadenylation site; this sequence may be involved in the expression or regulation of alpha-globin genes.
Mortality and Morbidity From Injuries in Sports and Recreation
Authors: Jess F. Kraus, Carol Conroy
Journal: Annual Review of Public Health (1984)

Injuries from nonintentional causes resulted in 102,130 deaths in the US population during 1981 (70). In this same year 70,214,976 persons required either medical attention or a day of restricted activity because of injuries from all causes (10). The known-and admittedly incomplete-impact, economic and otherwise, of these injuries included over 144 million bed days of disabil­ ity, almost 493 million days of restricted activity, and over 14 million days lost from school by children aged 6 to 16 years. Injuries and adverse effects from all causes accounted for over 8% of all office visits to physicians in 198 1 (60) and almost 5 million physician contacts per month (estimated) (18). Furthermore, in 1981 nonintentional injuries and adverse effects accounted for an estimated annual total of 2,587,140 potential years lost before age 65 (17). This figure is almost 50% greater than the number of potential years of life lost before age 65 due to malignant neoplasms or diseases of the heart , the two leading causes of death in the US. The current system for classification and coding of cause of death and morbidity does not permit a description of activities surrounding the death or injury; therefore, an accurate annual count of deaths and injuries from athletics or recreational activities in the US is not possible. For example, a person struck by a car and killed would be classified as a pedestrian fatality; there would be no way of knowing from the International Classification of Diseases rubric (i.e. E81O. 7-819.7) whether the pedestrian was struck while crossing a street on the way to work (nonrecreational), jogging on a street in a park (recreational), or running in a marathon (sport). The only remedy for this problem would be to
CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS
Authors: Oswald T. Avery, Walther F. Goebel
Journal: The Journal of Experimental Medicine (1931)

1. Type-specific antipneumococcus immunity has been induced in rabbits by immunization with antigen prepared by combining a specific derivative of the capsular polysaccharide of Type III Pneumococcus with globulin from horse serum. 2. Rabbits immunized with this antigen acquire active immunity against infection with virulent Type III pneumococci. 3. The sera of the immune rabbits contain type-specific antibodies which precipitate the Type III capsular polysaccharide, agglutinate Type III pneumococci, and specifically protect mice against Type III infection. 4. The experimental data are discussed with reference to: (1) the concurrence in the immune sera of type-specific antibodies for Pneumococcus and precipitins for horse globulin; (2) the determining influence of the capsular polysaccharide on the specificity of the antigen as a whole; (3) the unity of the type-specific precipitins, agglutinins, and protective antibodies induced by a single component of the pneumococcus in chemical union with an unrelated, animal protein.
The postnatal decline of hemoglobin F synthesis in normal full-term infants.
Authors: H Bard
Journal: Journal of Clinical Investigation (1975)

Studies were carried out during the 1st yr of life in normal infants born at term to determine the proportions of fetal hemoglobin (Hb F) and adult hemoglobin (Hb A) being synthesized, in order to describe the complete switchover from Hb F to Hb A synthesis during postnatal life. 53 blood samples from 37 infants were incubated in an amino acid mixture containing [14C]leucine and chromatographed on DEAE-Sephadex for separation of Hb F and Hb A fractions. The completeness of the CEAE-Sephadex separation of Hb A and Hb F at an age when the major portion of synthesis was of the adult type of hemoglobin was confirmed by globin chain chromatography with the use of carboxylmethyl cellulose. There was a rapid decline in Hb F synthesis postnatally until 16-20 wk of age when levels of 3.2% plus or minus SD 2.1% were reached. By combining this data with that previously published, the complete switchover from Hb F to Hb A synthesis can be described in humans in relation to postconceptional age. It follows a sigmoid curve; the steep portion, which lies between the 30th and 52nd postconceptional week, is preceded and follwoed by plateaus averaging 95% and 7% Hb F synthesis, respectively.
Hemodynamic Characteristics of Patients with Hypothermia Due to Occult Infection and Other Causes
Authors: D. LYNN MORRIS
Journal: Annals of Internal Medicine (1985)

Eighty-five consecutive patients with hypothermia were prospectively evaluated to assess clinical and laboratory data that would differentiate those patients with hypothermia caused by severe infection and bacteremia and those with hypothermia of other causes. Thirty-two patients had hemodynamic monitoring, allowing us to assess hemodynamic differences between the two groups. Clinical characteristics, including admission temperature, leukocyte count, mean arterial pressure, pulse rate, respiratory rate, arterial pH, and pulmonary capillary wedge pressure, did not distinguish between the two groups. However, patients with infection with bacteremia had lower calculated systemic vascular resistances (486.0 ±125.0 compared with 1759.9 ±331.0 dynes s cm-5;p = 0.001) and higher cardiac indices (7.1 ±1.9 compared with 2.8 ±0.7 L/min m2; ñ = 0.006) than patients without severe infections. Thus, our data suggest that hemodynamic characteristics are different in patients with infection-related hypothermia and patients with hypothermia associated with other causes, and appear to depend on the underlying disease.
GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO
Authors: Judith A. Kapp, Carl W. Pierce, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1974)

Although nonresponder, H-2s and H-2q, mice fail to develop GAT-specific PFC responses to GAT, they do develop GAT-specific PFC responses when stimulated by GAT complexed to an immunogenic carrier such as methylated bovine serum albumin. The studies described in this paper show that injection of nonresponder mice with GAT specifically decreases their ability to develop anti-GAT PFC responses to a subsequent challenge with GAT-MBSA. Addition of GAT to cultures of spleen cells from nonresponder mice also prevents development of the GAT-specific PFC responses stimulated by GAT-MBSA. Thus, interaction of nonresponder spleen cells with GAT leads to the induction of unresponsiveness in vivo and in vitro. Various parameters of the tolerance induction have been investigated and described. A comparison of the effects of GAT on B cells indicates that nonresponder B cells are more readily rendered unresponsive by soluble GAT than are responder B cells. The significance of these data for our understanding of Ir gene regulation of the immune response is discussed.
Pulmonary Prostacyclin Synthase Overexpression Chemoprevents Tobacco Smoke Lung Carcinogenesis in Mice
Authors: Robert L. Keith, York E. Miller, Tyler M. Hudish, Carlos E. Girod, Sylk Sotto-Santiago, Wilbur A. Franklin, Raphael A. Nemenoff, Thomas H. March, S. Patrick Nana-Sinkam, Mark W. Geraci
Journal: Cancer Research (2004)

Abstract Increased pulmonary production of prostaglandin I2 (prostacyclin) by lung-specific overexpression of prostacyclin synthase decreases lung tumor incidence and multiplicity in chemically induced murine lung cancer models. We hypothesized that pulmonary prostacyclin synthase overexpression would prevent lung carcinogenesis in tobacco-smoke exposed mice. Murine exposure to tobacco smoke is an established model of inducing pulmonary adenocarcinomas and allows for the testing of potential chemopreventive strategies. Transgenic FVB/N mice with lung-specific prostacyclin synthase overexpression were exposed to mainstream cigarette smoke for 22 weeks and then held unexposed for an additional 20 weeks. All of the exposed animals developed bronchiolitis analogous to the respiratory bronchiolitis seen in human smokers. The transgenic mice, when compared with smoke-exposed transgene negative littermates, had significant decreases in tumor incidence and multiplicity. Significantly fewer transgenics (6 of 15; 40%) developed tumors compared with the tumor incidence in wild-type littermates (16 of 19; 84%; Fisher’s exact test, P = 0.012). Tumor multiplicity was also significantly decreased in the transgenic animals (tg+ = 0.4 ± 0.5 versus wild-type = 1.2 ± 0.86 tumors/mouse; P &amp;lt; 0.001). Targeted prostaglandin levels at the time of sacrifice revealed significantly elevated prostaglandin I2 levels in the transgenic animals, coupled with significantly decreased prostaglandin E2 levels. Gene expression analysis of isolated type II pneumocytes suggests potential explanations for the observed chemoprevention, with Western blot analysis confirming decreased expression of cytochrome p450 2e1. These studies extend our previous studies and demonstrate that manipulation of prostaglandin production distal to cyclooxygenase significantly reduces lung carcinogenesis in a tobacco smoke exposure model, and gene expression studies show critical alterations in antioxidation, immune response, and cytokine pathways.
Cardiac Conduction in Patients with Symptomatic Sinus Node Disease
Authors: KENNETH M. ROSEN, HENRY S. LOEB, M. ZIAD SINNO, SHAHBUDIN H. RAHIMTOOLA, ROLF M. GUNNAR
Journal: Circulation (1971)

Cardiac conduction was investigated at the time of pacemaker insertion in 15 patients with symptomatic sinus node disease. Techniques included recording of His bundle potentials, atrial pacing at various heart rates, and atropine administration. Atrioventricular (AV) conduction was impaired in eight patients who manifested one or more of the following: P-R prolongation, P-H prolongation, and development of second degree AV block with atrial pacing at heart rates below 130 beats/min. Five patients had intraventricular conduction defects diagnosed electrocardiographically; none of these had H-Q prolongation. One of these five, with left bundle-branch block, subsequently developed complete heart block and had a calcific lesion involving the His bundle. Depression of cardiac automaticity was noted in four patients, with asystolic periods greater than 2 sec after sudden cessation of atrial pacing at rates of 100-160 beats/min. Responses to 1 mg of intravenous atropine were varied, but no patient developed sinus rates greater than 90 beats/min, suggesting the presence of primary sinus node dysfunction. In conclusion, abnormalities of conduction and automaticity in specialized tissue in addition to the sinus node are common in patients with symptomatic sinus node disease. These abnormalities should be recognized when present, so that the ideal site for permanent pacing may be chosen.
Extensive and Continuous Duplication Facilitates Rapid Evolution and Diversification of Gene Families
Authors: Dan Chang, Thomas F. Duda
Journal: Molecular Biology and Evolution (2012)

The origin of novel gene functions through gene duplication, mutation, and natural selection represents one of the mechanisms by which organisms diversify and one of the possible paths leading to adaptation. Nonetheless, the extent, role, and consequences of duplications in the origins of ecological adaptations, especially in the context of species interactions, remain unclear. To explore the evolution of a gene family that is likely linked to species associations, we investigated the evolutionary history of the A-superfamily of conotoxin genes of predatory marine cone snails (Conus species). Members of this gene family are expressed in the venoms of Conus species and are presumably involved in predator–prey associations because of their utility in prey capture. We recovered sequences of this gene family from genomic DNA of four closely related species of Conus and reconstructed the evolutionary history of these genes. Our study is the first to directly recover conotoxin genes from Conus genomes to investigate the evolution of conotoxin gene families. Our results revealed a phenomenon of rapid and continuous gene turnover that is coupled with heightened rates of evolution. This continuous duplication pattern has not been observed previously, and the rate of gene turnover is at least two times higher than estimates from other multigene families. Conotoxin genes are among the most rapidly evolving protein-coding genes in metazoans, a phenomenon that may be facilitated by extensive gene duplications and have driven changes in conotoxin functions through neofunctionalization. Together these mechanisms led to dramatically divergent arrangements of A-superfamily conotoxin genes among closely related species of Conus. Our findings suggest that extensive and continuous gene duplication facilitates rapid evolution and drastic divergence in venom compositions among species, processes that may be associated with evolutionary responses to predator–prey interactions.