tbuckley/cabot-search huggingface dataset:
Minor Fitness Costs in an Experimental Model of Horizontal Gene Transfer in Bacteria
Authors: Anna Knöppel, Peter A. Lind, Ulrika Lustig, Joakim Näsvall, Dan I. Andersson
Journal: Molecular Biology and Evolution (2014)

Genes introduced by horizontal gene transfer (HGT) from other species constitute a significant portion of many bacterial genomes, and the evolutionary dynamics of HGTs are important for understanding the spread of antibiotic resistance and the emergence of new pathogenic strains of bacteria. The fitness effects of the transferred genes largely determine the fixation rates and the amount of neutral diversity of newly acquired genes in bacterial populations. Comparative analysis of bacterial genomes provides insight into what genes are commonly transferred, but direct experimental tests of the fitness constraints on HGT are scarce. Here, we address this paucity of experimental studies by introducing 98 random DNA fragments varying in size from 0.45 to 5 kb from Bacteroides, Proteus, and human intestinal phage into a defined position in the Salmonella chromosome and measuring the effects on fitness. Using highly sensitive competition assays, we found that eight inserts were deleterious with selection coefficients (s) ranging from ≈ −0.007 to −0.02 and 90 did not have significant fitness effects. When inducing transcription from a PBAD promoter located at one end of the insert, 16 transfers were deleterious and 82 were not significantly different from the control. In conclusion, a major fraction of the inserts had minor effects on fitness implying that extra DNA transferred by HGT, even though it does not confer an immediate selective advantage, could be maintained at selection-transfer balance and serve as raw material for the evolution of novel beneficial functions.
Hypermethylation of the 5′ CpG Island of the <b> <i>FHIT</i> </b> Gene Is Associated with Hyperdiploid and Translocation-Negative Subtypes of Pediatric Leukemia
Authors: Shichun Zheng, Xiaomei Ma, Luoping Zhang, Laura Gunn, Martyn T. Smith, Joseph L. Wiemels, Kenneth Leung, Patricia A. Buffler, John K. Wiencke
Journal: Cancer Research (2004)

Abstract The human FHIT (fragile histidine triad) gene is a putative tumor suppressor gene located at chromosome region 3p14.2. Previous studies have shown that loss of heterozygosity, homozygous deletions, and abnormal expression of the FHIT gene are involved in several types of human malignancies. A CpG island is present in the 5′ promoter region of the FHIT gene, and methylation in this region correlates with loss of FHIT expression. To test whether aberrant methylation of the FHIT gene may play a role in pediatric leukemia, we assessed the FHIT methylation status of 10 leukemia cell lines and 190 incident population-based cases of childhood acute lymphocytic and myeloid leukemias using methylation-specific PCR. Conventional and fluorescence in situ hybridization cytogenetic data were also collected to examine aneuploidy, t(12, 21), and other chromosomal rearrangements. Four of 10 leukemia cell lines (40%) and 52 of 190 (27.4%) bone marrows from childhood leukemia patients demonstrated hypermethylation of the promoter region of FHIT. Gene expression analyses and 5-aza-2′-deoxycytidine treatment showed that promoter hypermethylation correlated with FHIT inactivation. Among primary leukemias, hypermethylation of FHIT was strongly correlated with acute lymphoblastic leukemia (ALL) histology (P = 0.008), high hyperdiploid (P &amp;lt; 0.0001), and translocation-negative (P &amp;lt; 0.0001) categories. Hyperdiploid B-cell ALLs were 23-fold more likely to be FHIT methylated compared with B-cell ALL harboring TEL-AML translocations. FHIT methylation was associated with high WBC counts at diagnosis, a known prognostic indicator. These results suggest that hypermethylation of the promoter region CpG island of the FHIT gene is a common event and may play an important role in the etiology and pathophysiology of specific cytogenetic subtypes of childhood ALL.
Acute reduction in human platelet alpha 2-adrenoreceptor affinity for agonist by endogenous and exogenous catecholamines.
Authors: A S Hollister, G A FitzGerald, J H Nadeau, D Robertson
Journal: Journal of Clinical Investigation (1983)

The binding characteristics of l-epinephrine to intact human platelets were assessed under conditions of physiological and pharmacological variations in plasma catecholamine concentration. In competition with the alpha 2-adrenoreceptor antagonist yohimbine, mean platelet receptor affinity for l-epinephrine was decreased 3.4-fold after 2 h of upright posture and exercise. This change in agonist affinity correlated significantly with the increases in plasma epinephrine and norepinephrine that were stimulated by upright posture and exercise. Supine subjects infused with l-norepinephrine or l-epinephrine for 2 h also averaged a 3.3- and 2.7-fold decrease in platelet alpha 2-adrenoreceptor affinity for agonist with no change in receptor number or antagonist affinity. The alpha 2-adrenoreceptor agonist affinity changes were specific for alpha-agonists since they were blocked by phentolamine, and incubation with 10(-5) M isoproterenol produced no change in alpha 2-adrenoreceptor affinity for l-epinephrine. In vitro exposure of intact human platelets to 10(-6) to 10(-10) M l-epinephrine for 2 h produced a concentration-related decrease in alpha 2-adrenoreceptor affinity for agonist. In all three paradigms, average slope factors approached 1.0 as affinity decreased, which is consistent with a heterogeneous receptor population that becomes more homogeneous after agonist exposure. Incubation of platelet-rich plasma with 10(-6) to 10(-8) M l-epinephrine resulted in a dose- and time-related loss of aggregatory response to l-epinephrine; this demonstrates that agonist affinity changes are correlated with changes in receptor sensitivity. These observations demonstrate that physiological variations in plasma catecholamines acutely modulate the intact human platelet alpha 2-adrenoreceptor's affinity for agonist, and can thereby alter the sensitivity of platelets to alpha 2-adrenergic agonist.
After the Early Hype, Interferons Spark Interest
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article After the Early Hype, Interferons Spark Interest Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 10, 19 May 1993, Pages 773–775, https://doi.org/10.1093/jnci/85.10.773 Published: 19 May 1993
Exposure of Neonatal Rats to Parathion Elicits Sex-Selective Reprogramming of Metabolism and Alters the Response to a High-Fat Diet in Adulthood
Authors: T. Leon Lassiter, Ian T. Ryde, Emiko A. MacKillop, Kathleen K. Brown, Edward D. Levin, Frederic J. Seidler, Theodore A. Slotkin
Journal: Environmental Health Perspectives (2008)

Developmental exposures to organophosphate pesticides are virtually ubiquitous. These agents are neurotoxicants, but recent evidence also points to lasting effects on metabolism.We administered parathion to neonatal rats. In adulthood, we assessed the impact on weight gain, food consumption, and glucose and lipid homeostasis, as well as the interaction with the effects of a high-fat diet.Neonatal rats were given parathion on postnatal days 1-4 using doses (0.1 or 0.2 mg/kg/day) that straddle the threshold for barely detectable cholinesterase inhibition and the first signs of systemic toxicity. In adulthood, animals were either maintained on standard lab chow or switched to a high-fat diet for 7 weeks.In male rats on a normal diet, the low-dose parathion exposure caused increased weight gain but also evoked signs of a prediabetic state, with elevated fasting serum glucose and impaired fat metabolism. The higher dose of parathion reversed the weight gain and caused further metabolic defects. Females showed greater sensitivity to metabolic disruption, with weight loss at either parathion dose, and greater imbalances in glucose and lipid metabolism. At 0.1 mg/kg/day parathion, females showed enhanced weight gain on the high-fat diet; This effect was reversed in the 0.2-mg/kg/day parathion group, and was accompanied by even greater deficits in glucose and fat metabolism.Neonatal low-dose parathion exposure disrupts glucose and fat homeostasis in a persistent and sex-selective manner. Early-life toxicant exposure to organophosphates or other environmental chemicals may play a role in the increased incidence of obesity and diabetes.
Differences Between Clinical and Research Practices in Diagnosing Borderline Personality Disorder
Authors: Mark Zimmerman, Jill I. Mattia
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: It has been reported that clinicians are less inclined than researchers to use direct questions in ascertaining the presence of personality disorders, and questions have been raised about the validity of research on personality disorders in which diagnoses are based on semistructured diagnostic interviews. This study examined the influence of assessment method on the diagnosis of borderline personality disorder. METHOD: Diagnoses of borderline personality disorder derived from structured and unstructured clinical interviews were compared in two groups of psychiatric outpatients seen in the same practice setting. Five hundred individuals presenting to a general adult psychiatric practice for an intake appointment underwent a routine unstructured clinical interview. After the completion of that study, the method of conducting diagnostic evaluations was changed, and 409 individuals were interviewed with the borderline personality disorder section of the Structured Interview for DSM-IV Personality. RESULTS: Individuals in the structured interview group were significantly more often diagnosed with borderline personality disorder than individuals in the clinical group. When information from the structured interview was presented to the clinicians, borderline personality disorder was much more likely to be diagnosed by them. CONCLUSIONS: The method used to assess borderline personality disorder has a great impact on the frequency with which it is diagnosed. Without the benefit of detailed information from a semistructured diagnostic interview, clinicians rarely diagnose the disorder during a routine intake evaluation. Providing the results of a semistructured interview to clinicians prompts them to diagnose borderline personality disorder much more frequently. This is inconsistent with the notion that personality disorder diagnoses based on semistructured interviews are not viewed as valid by clinicians.
Arlm1 is a male-specific modifier of astrocytoma resistance on mouse Chr 12
Authors: J. C. Amlin-Van Schaick, S. Kim, C. DiFabio, M.-H. Lee, K. W. Broman, K. M. Reilly
Journal: Neuro-Oncology (2012)

While many cancers show a sex bias, the genetic basis and molecular mechanisms underlying sex bias are not always clear. Astrocytoma and glioblastoma show male predominance in humans. We have shown previously that glial tumors forming in the Nf1−/+; Trp53−/+cis (NPcis) mouse model also show a sex bias in some genetic contexts. Using cross-species comparisons we have identified candidate male-specific modifiers of astrocytoma/glioblastoma. Linkage analysis of B6X(B6X129)-NPcis mice identifies a modifier of astrocytoma resistance specific to males, named Arlm1, on distal mouse Chr 12. Arlm1 is syntenic to human Chr 7p15, 7p21, 7q36, and 14q32 regions that are altered in human glioblastoma. A subset of these genes shows male-specific correlations to glioblastoma patient survival time and represents strong candidates for the Arlm1 modifier gene. Identification of male-specific modifier genes will lead to a better understanding of the molecular basis of male predominance in astrocytoma and glioblastoma.
Is Failure to Meet Spiritual Needs Associated With Cancer Patients' Perceptions of Quality of Care and Their Satisfaction With Care?
Authors: Alan B. Astrow, Ann Wexler, Kenneth Texeira, M. Kai He, Daniel P. Sulmasy
Journal: Journal of Clinical Oncology (2007)

Few studies regarding patients' views about spirituality and health care have included patients with cancer who reside in the urban, northeastern United States. Even fewer have investigated the relationship between patients' spiritual needs and perceptions of quality and satisfaction with care.Outpatients (N = 369) completed a questionnaire at the Saint Vincent's Comprehensive Cancer Center in New York, NY. The instrument included the Quality of End-of-Life Care and Satisfaction with Treatment quality-of-care scale and questions about spiritual and religious beliefs and needs.The participants' mean age was 58 years; 65% were female; 67% were white; 65% were college educated; and 32% had breast cancer. Forty-seven percent were Catholic; 19% were Jewish; 16% were Protestant; and 6% were atheist or agnostic. Sixty-six percent reported that they were spiritual but not religious. Only 29% attended religious services at least once per week. Seventy-three percent reported at least one spiritual need; 58% thought it appropriate for physicians to inquire about their spiritual needs. Eighteen percent reported that their spiritual needs were not being met. Only 6% reported that any staff members had inquired about their spiritual needs (0.9% of inquiries by physicians). Patients who reported that their spiritual needs were not being met gave lower ratings of the quality of care (P = .009) and reported lower satisfaction with care (P = .006).Most patients had spiritual needs. A slight majority thought it appropriate to be asked about these needs, although fewer thought this compared with reports in other settings. Few had their spiritual needs addressed by the staff. Patients whose spiritual needs were not met reported lower ratings of quality and satisfaction with care.
Diagnostic Marker Cooperative Study for the Diagnosis of Myocardial Infarction
Authors: Janice Zimmerman, Robert Fromm, Denise Meyer, Ann Boudreaux, Chuan-Chuan C. Wun, Richard Smalling, Barry Davis, Gabriel Habib, Robert Roberts
Journal: Circulation (1999)

Background —Millions of patients present annually with chest pain, but only 10% to 15% have myocardial infarction. Lack of diagnostic sensitivity and specificity of clinical and conventional markers prevents or delays treatment and leads to unnecessary costly admissions. Comparative data are lacking on the new markers, yet using all of them is inappropriate and expensive. Methods and Results —The Diagnostic Marker Cooperative Study was a prospective, multicenter, double-blind study with consecutive enrollment of patients with chest pain presenting to the emergency department. Diagnostic sensitivity and specificity and frequency of increase in patients with unstable angina were determined for creatine kinase-MB (CK-MB) subforms, myoglobin, total CK-MB (activity and mass), and troponin T and I on the basis of frequent serial sampling for ≤24 hours. Of 955 patients with chest pain, 119 (12.5%) had infarction identified by use of CK-MB mass, and 203 (21%) had unstable angina. CK-MB subforms were most sensitive and specific (91% and 89%) within 6 hours of onset, followed by myoglobin (78% and 89%). For late diagnosis, total CK-MB activity (derived from subforms) was the most sensitive and specific (96% and 98%) at 10 hours from onset, followed by troponin I (96% and 93%), but not until 18 hours, and troponin T (87% and 93% at 10 hours). In unstable angina, CK-MB subforms were increased in 29.5%, myoglobin in 23.7%, troponin I in 19.7%, and troponin T in 14.8%. All markers were increased in 99 patients. With each marker as the diagnostic standard, CK-MB subforms and myoglobin remained the most sensitive for early diagnosis. Conclusions —The CK-MB subform assay alone or in combination with a troponin reliably triages patients with chest pain and should lead to improved therapy and reduced cost.
Exhaled Nitric Oxide as a Diagnostic Test for Asthma
Authors: Aaron Deykin, Anthony F. Massaro, Jeffrey M. Drazen, Elliot Israel
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Measurement of the fraction of exhaled nitric oxide (FeNO) has been proposed as a noninvasive assessment of asthmatic airway inflammation. The influence of the expiratory flow rate during the collection maneuver on the ability of FeNO to discriminate healthy subjects from those with asthma is unknown. We compared online and offline measurement of FeNO at different flow rates. FeNO was collected with expiratory flows of 50–500 ml/second in 34 patients with asthma (PC20 of less than 8 mg/ml) and 28 healthy subjects (PC20 of more than 10 mg/ml) using offline collection techniques. In a subgroup of 18 individuals with asthma and 17 healthy subjects, we additionally measured FeNO at multiple expiratory flow rates (47–250 ml/second) using online methods. FeNO fell with an increasing expiratory flow rate; FeNO was higher in subjects with asthma as compared with healthy subjects at each flow rate studied with both techniques (p < 0.001). Receiver operating characteristic (ROC) curves for the diagnosis of asthma indicated that FeNO is a robust discriminator between individuals with asthma and healthy subjects (area under the ROC curves 0.79 ± 0.06 to 0.86 ± 0.06, p for significant discrimination < 0.0001). Neither expiratory flow rate nor collection technique (online versus offline) significantly altered this discriminatory capacity (area under the ROC curves = 0.84 ± 0.07 with the slowest online method versus 0.80 ± 0.07 with the fastest offline method, p = 0.46). These data indicate that the choice of expiratory flow rate and collection method can be based on practicality and patient comfort without compromising the utility of this test for asthma.
Does physical trauma lead to an increase in the risk of new onset widespread pain?
Authors: G Wynne-Jones
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To determine the rate of new onset of widespread pain after a traumatic event (motor vehicle crash). <b>Methods:</b> A prospective cohort study of persons registered with an insurance company who had or had not experienced a motor vehicle crash. All participants were sent a questionnaire to assess pre-crash (or for the non-crash group, prior) psychosocial factors and widespread pain. Participants reporting pre-crash (prior) widespread pain were excluded. At six months, participants were sent a follow up questionnaire to ascertain new prevalent widespread pain. <b>Results:</b> 597 (51%) of participants returned a baseline questionnaire (465 crash and 132 non-crash). Among the cohort who had experienced a crash, the new onset rate of widespread pain six months later was low (8%), though in comparison with the non-crash group there was an increased risk (RR = 1.9 (95% CI, 0.8 to 4.8, adjusted for age and sex)); this was attenuated after adjustment for pre-crash (prior) psychological distress and somatic symptoms (RR = 1.4 (95% CI, 0.5 to 3.2)). <b>Conclusions:</b> The findings suggest that a motor vehicle crash (as an example of a physically traumatic event) is unlikely to have a major impact on the new onset of widespread pain. Any observed relation may, in part, be explained by psychological distress.
Immunological Prevention of a Multigene Cancer Syndrome
Authors: Stefania Croci, Giordano Nicoletti, Lorena Landuzzi, Carla De Giovanni, Annalisa Astolfi, Chiara Marini, Emma Di Carlo, Piero Musiani, Guido Forni, Patrizia Nanni, Pier-Luigi Lollini
Journal: Cancer Research (2004)

Abstract Vaccines effectively prevent the onset of tumors in transgenic mice carrying activated oncogenes; however, human tumors are caused by combined alterations in oncogenes and oncosuppressor genes. We evaluated the impact of prophylactic vaccines in HER-2/neu transgenic, p53 wild-type/null mice that succumb to an aggressive cancer syndrome comprising mammary and salivary gland carcinomas and rhabdomyosarcoma. A vaccine made of allogeneic mammary carcinoma cells expressing HER-2/neu and interleukin 12 afforded long-term protection from tumor onset. Tumor prevention was mediated by T cell–derived cytokines, in particular γ-interferon, and by anti–HER-2/neu antibodies. HER-2/neu expression was inhibited in target tissues of vaccinated mice, and somatic loss of the wild-type p53 allele did not occur. A highly effective vaccine against a single oncoprotein induced a powerful immune response that arrested multistep carcinogenesis in distinct target tissues.
Binding of Cytosolic Proteins to Myofibrils in Ischemic Rat Hearts
Authors: Roberta Barbato, Roberta Menabò, Paola Dainese, Ernesto Carafoli, Stefano Schiaffino, Fabio Di Lisa
Journal: Circulation Research (1996)

Abstract Myofibrillar proteins (MPs) were extracted from isolated and perfused rat hearts subjected to different periods of ischemia to investigate the occurrence of protein degradation and/or the association of cytosolic proteins with the myofibrillar pellet. A 23-kD band was detected by SDS-PAGE of MPs after 5 minutes of ischemia, with its density gradually increasing to a plateau after 20 minutes. Longer periods of ischemia were associated with the appearance of a 39-kD band. Irrespective of the duration of ischemia, both these bands persisted during reperfusion. A partial proteolytic degradation of troponin T (TnT) and troponin I (TnI) has been claimed to be responsible for the generation of these peptides. However, the N-terminal sequence of the 39-kD band was identical to that of GAPDH, whereas Edman sequencing after pepsin digestion showed that the 23 kD is αB-crystallin. The binding of the two cytosolic proteins to myofibrils was confirmed by immunofluorescence analysis on cryosections of ischemic hearts. In vitro studies showed that acidosis was sufficient to induce the binding of αB-crystallin, whereas the inhibition of ATP depletion prevented the binding of GAPDH. Thiol oxidation is unlikely to promote GAPDH binding, since perfusion with iodoacetate under aerobic conditions or treatment of homogenates with N -ethylmaleimide or diamide failed to induce GAPDH association with the myofibrils. These changes of the myofibrillar proteins could be considered as intracellular markers of the evolution of the ischemic damage. In addition, the binding of the 23-kD peptide might be involved in alterations of contractility.
Release of Immune Complexes Bound to CR1 on Erythrocytes; Suramin Inhibits Factor I in the Presence of EDTA
Authors: B. S. Thomsen, H. Nielsen, G. Bendixen
Journal: Allergy (1986)

An experimental model was established in order to study the release of immune complexes (IC) bound by complement C3b receptors (CR1) on human erythrocytes (RBC). Soluble tetanus toxoid anti‐tetanus toxoid complexes were incubated with RBC in the presence of autologous serum at optimal conditions for binding. The RBC carrying complement‐opsonized complexes were incubated with appropriate serum reagents, and ii was shown that factor I was required for release of the complexes, which occurred without loss of CR1. Suramin was, irrespective of factor I, found to induce release of CR1‐bound IC in the absence of EDTA, whereas factor I‐mediated release was inhibited by soramin in the presence of EDTA. EDTA probably interfered through a charge‐dependent interaction. These observations are decisive for the interpretation of in vitro experiments involving these reagents. The combination of EDTA and suramin was found inappropriate for use in quantitative determination of in vivo CR1‐bound IC.