tbuckley/cabot-search huggingface dataset:
Application of the Isolation with Migration Model Demonstrates the Pleistocene Origin of Geographic Differentiation in Cardamine nipponica (Brassicaceae), an Endemic Japanese Alpine Plant
Authors: Hajime Ikeda, Noriyuki Fujii, Hiroaki Setoguchi
Journal: Molecular Biology and Evolution (2009)

The Pleistocene was characterized by a cyclic pattern of cold and warm climatic periods, or climatic oscillations, which caused fluctuations in the distributions of organisms. This resulted in drastic changes in demography, thereby accelerating the genetic divergence of populations. Phylogeographic studies have elucidated the history of populations during the Pleistocene. However, given the lack of model-based analysis of population histories, previous phylogeographic studies could not adequately evaluate the effect of these Pleistocene climatic oscillations on the genetic divergence and migration events between populations. Populations of Japanese alpine plants in central and northern Japan are highly differentiated, and a history of isolation between regions during the Pleistocene was inferred. Using sequences of 10 nuclear genes (ca. approximately 7,000 bp in total) from Cardamine nipponica (Brassicaceae), we applied an isolation with migration (IM) model to test the significance of the isolation history between central and northern Japan and to assess whether range shifts during the Pleistocene climatic oscillations were involved in the genetic differentiation between regions. The estimated divergence time indicates that the two regions were separated about 100,000–110,000 years ago. The exclusive occurrence of closely related haplotypes within each region (parsimony network) and the high level of genetic differentiation between the regions (mean FST = 0.417) indicate that genetic divergence occurred following the isolation of the two regions. Therefore, the genetic differentiation between regions was shaped during the Pleistocene, especially during the last glacial and inter and postglacial periods. In addition, our multilocus analysis showed that populations in central and northern Japan were completely isolated after they split. Geographic separation and subsequent restricted migration events among mountains could explain this isolation history between regions. Furthermore, genetic drift in the reduced populations would remove evidence of occasional migration, emphasizing the isolation history. Therefore, our application of a demographic model demonstrated the Pleistocene origin of geographic differentiation statistically and provided a plausible migration history for C. nipponica.
Reversal of depressant effects of propranolol on the left ventricular pump function by nifedipine in dogs with chronic ischaemia
Authors: M. TANl, H. YAMAZAKI, S. NOMA, S. OHNISHI, S. HANDA, Y. NAKAMURA
Journal: Cardiovascular Research (1986)

The aim of this study was to clarify the combined effects of propranolol and nifedipine on the regional wall motion and haemodynamic variables of the heart in dogs with chronic ischaemia. After an injection of propranolol the heart rate and stroke volume significantly decreased (from 128(18) beats·min−1 to 113(12) beats min−1 and from 15.1(3.1) ml to 12.2(2.6) ml respectively) and the left ventricular end diastolic pressure and systemic vascular resistance in systole increased significantly (from 7.3(1.5) mmHg to 10.0(1.8) mmHg and from 8.61(1.42) kPa·litre−1·min−1 to 11.80(1.59) kPa·litre−1·min−1 respectively). In the regional myocardium the end diastolic length increased significantly in both border and normal zones (7(3)% and 4(2)% respectively) and the percentage systolic shortening in the normal zone decreased significantly from 18.0(3.1)% to 15.1(2.9)%. In the border and infarcted zones the percentage systolic shortening or systolic lengthening did not change. The administration of nifedipine resulted in significant decreases in left ventricular systolic pressure and in systemic vascular resistance (from 122(17) mmHg to 105(14) mmHg and from 11.80(1.59) kPa·litre−1·min−1 to 6.63(1.24) kPa·litre−1·min−1 respectively) and stroke volume increased to 18.2(4.4) ml. The percentage systolic shortening in the border and normal zones improved significantly to 9.8(3.2)% and 19.2(3.7)% respectively without any change in end diastolic length and left ventricular end diastolic pressure. In the infarcted zone no significant change in systolic lengthening or end diastolic length was seen. Thus impaired left ventricular pump function induced by propranolol was reversed by nifedipine.
Pharmacological Characterization of Adrenergic Alpha and Beta Receptors Mediating the Vasomotor Responses of Cerebral Arteries Ir Vitro
Authors: LARS EDVINSSON, CHRISTER OWMAN
Journal: Circulation Research (1974)

The adrenergic receptors in the isolated feline middle cerebral artery were characterized pharmacologically using a sensitive system for recording circular contractions in vitro. Epinephrine. norepinephrine, isoproterenol. and phenylephrine contracted the vessel in the mentioned order of potency. Together with the inhibitory patterns obtained with graded doses of piperoxan (reversible competitive inhibition) and dibenamine or phenoxybenzamine (irreversible competitive inhibition), these results showed that the contraction was mediated by alpha receptors. With piperoxan and norepinephrine, the mean value for pA 2 was 7.06 and for K H 1.24 x 10 -7 M. The mean value for K A calculated for norepinephrine before and after partial irreversible blockade of the alpha receptors with phenoxybenzamine was 1.73 x 10 -6 M. The norepinephrine response was not directly proportional to the amount of receptors occupied; ED 50 was reached when only about 11% of the receptors were occupied and the E Am response was obtained when 75% of the receptors were occupied. Dilation was achieved only after an active tonic contraction had been induced (with 5-hydroxytryptamine) in the vessels, and the order of potency was isoproterenol &gt; norepinephrine - epinephrine &gt; terbutaline. Inhibition with INPEA and propranolol was competitive, as confirmed by Arunlakshana-Schild plots, showing that the dilatory response was a beta-receptor effect. The values for pA 2 (8.78 and 9.17) and K H (2.31 x 10 -9 M and 1.77 x 10 -9 M) for propranolol were indistinguishable in tests with terbutaline and isoproterenol, respectively. Comparison of the relative potencies of norepinephrine and epinephrine as well as isoproterenol and terbutaline suggested that the receptors were of the beta 1 type.
Relationship between Serum Dopamine-β-Hydroxylase Activity, Catecholamine Metabolism, and Hemodynamic Changes during Paroxysmal Hypertension in Quadriplegia
Authors: N. ERIC NAFTCHI, G. FREDERICK WOOTEN, EDWARD W. LOWMAN, JULIUS AXELROD
Journal: Circulation Research (1974)

During the chronic phase of spinal cord injury, serum dopamine-β-hydroxylase activity, arterial blood pressure, and blood flow in the fourth finger, the hallux, and the calf were measured in nine quadriplegic subjects before, during, and after expansion of the urinary bladder. In addition, in five chronic quadriplegic subjects, serum dopamine-β-hydroxylase activity, urinary catecholamine metabolites, and arterial blood pressure were measured before and during spontaneous hypertensive episodes. There was a significant correlation between the different stages of hypertension, the serum dopamine-β-hydroxylase activity, and the concentration of urinary catecholamine metabolites. The highest levels were found at the height of intracystic pressure when the arterial blood pressure was at its maximum but the pulse rate had dropped to its lowest level. At the same time the blood flow in the upper and lower extremities and the calf musculature was below detection limits, and peripheral vascular resistance was markedly enhanced. Serum dopamine-β-hydroxylase and arterial blood pressure levels correlated directly with urinary concentrations of normetanephrine but not with those of metanephrine. The data provide evidence for an in vivo simultaneous, proportional release of dopamine-β-hydroxylase and norepinephrine, suggesting release by exocytosis. The data further show that dopamine can also be released together with norepinephrine and dopamine-β-hydroxylase as evidenced by increased urinary concentrations of its major catabolite, homovanillic acid, during hypertensive stress. The hypertensive response in quadriplegic subjects during routine test of bladder function renders these subjects ideal models for self-controlled studies of neurogenic hypertension and its biochemical parameters. The results indicate that hypertension in quadriplegia, whether spontaneous or induced, is caused by increased release of norepinephrine and that the half-life of dopamine-β-hydroxylase released during stress is shorter than that previously reported.
Evolution of Transcription Factor Binding Sites in Mammalian Gene Regulatory Regions: Conservation and Turnover
Authors: Emmanouil T. Dermitzakis, Andrew G. Clark
Journal: Molecular Biology and Evolution (2002)

Comparisons between human and rodent DNA sequences are widely used for the identification of regulatory regions (phylogenetic footprinting), and the importance of such intergenomic comparisons for promoter annotation is expanding. The efficacy of such comparisons for the identification of functional regulatory elements hinges on the evolutionary dynamics of promoter sequences. Although it is widely appreciated that conservation of sequence motifs may provide a suggestion of function, it is not known as to what proportion of the functional binding sites in humans is conserved in distant species. In this report, we present an analysis of the evolutionary dynamics of transcription factor binding sites whose function had been experimentally verified in promoters of 51 human genes and compare their sequence to homologous sequences in other primate species and rodents. Our results show that there is extensive divergence within the nucleotide sequence of transcription factor binding sites. Using direct experimental data from functional studies in both human and rodents for 20 of the regulatory regions, we estimate that 32%–40% of the human functional sites are not functional in rodents. This is evidence that there is widespread turnover of transcription factor binding sites. These results have important implications for the efficacy of phylogenetic footprinting and the interpretation of the pattern of evolution in regulatory sequences.
<i>In vivo</i> Real-time Tracking of Single Quantum Dots Conjugated with Monoclonal Anti-HER2 Antibody in Tumors of Mice
Authors: Hiroshi Tada, Hideo Higuchi, Tomonobu M. Wanatabe, Noriaki Ohuchi
Journal: Cancer Research (2007)

Studies with tracking of single nanoparticles are providing new insights into the interactions and processes involved in the transport of drug carriers in living mice. Here, we report the tracking of a single particle quantum dot (Qdot) conjugated with tumor-targeting antibody in tumors of living mice using a dorsal skinfold chamber and a high-speed confocal microscope with a high-sensitivity camera. Qdot labeled with the monoclonal anti-HER2 antibody was injected into mice with HER2-overexpressing breast cancer to analyze the molecular processes of its mechanistic delivery to the tumor. Movement of single complexes of the Qdot-antibody could be clearly observed at 30 frames/s inside the tumor through a dorsal skinfold chamber. We successfully identified six processes of delivery: initially in the circulation within a blood vessel, during extravasation, in the extracelullar region, binding to HER2 on the cell membrane, moving from the cell membrane to the perinuclear region, and in the perinuclear region. The six processes were quantitatively analyzed to understand the rate-limiting constraints on Qdot-antibody delivery. The movement of the complexes at each stage was "stop-and-go." The image analysis of the delivery processes of single particles in vivo provides valuable information on antibody-conjugated therapeutic nanoparticles, which will be useful in increasing therapeutic efficacy.
Genetic variants of coagulation factor XIII, postmenopausal estrogen therapy, and risk of nonfatal myocardial infarction
Authors: Alexander P. Reiner, Susan R. Heckbert, Hans L. Vos, Robert A. S. Ariëns, Rozenn N. Lemaitre, Nicholas L. Smith, Thomas Lumley, Thomas D. Rea, Lucia A. Hindorff, Gina D. Schellenbaum, Frits R. Rosendaal, David S. Siscovick, Bruce M. Psaty
Journal: Blood (2002)
Clinicopathologic Features and Long-term Outcomes of NUT Midline Carcinoma
Authors: Daniel E. Bauer, Chelsey M. Mitchell, Kelly M. Strait, Christopher S. Lathan, Edward B. Stelow, Sonja C. Lüer, Somala Muhammed, Andrew G. Evans, Lynette M. Sholl, Juan Rosai, Eugenia Giraldi, Richard P. Oakley, Carlos Rodriguez-Galindo, Wendy B. London, Stephen E. Sallan, James E. Bradner, Christopher A. French
Journal: Clinical Cancer Research (2012)

NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations.A clinical database was established using retrospective demographic and outcomes data available on all known cases of NMC. Questionnaires were completed by treating physicians. Pathologic, demographic, and clinical variables were assessed for 63 patients, the largest cohort of patients with NMC studied to date. Outcome data from 54 patients were available for survival analyses.The diagnosis of NMC has increased annually since 2007. Since 2009, there has been an observed increase in the age at diagnosis (P < 0.05). Geographic distribution of patients with NMC has been concentrated in the United States (n = 41, 65%). The median overall survival for patients with NMC was 6.7 months. The 2-year progression-free survival (PFS) was 9% with a 95% confidence interval (CI) of 1% to 17% [1-year PFS 15% (5-24%) and 2-year overall survival (OS) was 19% with a 95% CI of 7%-31% (1-year OS: 30% (27-34%)]. Multivariate analysis suggested that extent of surgical resection and initial radiotherapy were independent predictors of PFS and OS. Notably, no chemotherapeutic regimen was associated with improved outcome.NMC portends a poor prognosis among all squamous cell neoplasms and seems to be frequently unrecognized. The finding that conventional chemotherapy has been inadequate indicates a pressing need for the development of targeted therapeutics. Intensive local therapies such as gross total resection and radiotherapy might be associated with enhanced survival.
The Hjelp24 NIMI Ringerike obesity clinic: an inpatient programme to address morbid obesity in adults
Authors: Sverre Mæhlum, Kjersti Karoline Danielsen, Lena Klasson Heggebø, Janne Schiøll
Journal: British Journal of Sports Medicine (2010)

An inpatient programme for the treatment of morbidly obese patients is described. The programme targets physical training, nutrition and coping strategies for behaviour change management. The patients spend 14 weeks at the clinic followed by two 1-week visits 16 and 32 weeks postdischarge. Preliminary data from the 166 patients treated during 2006 are given.
Blood Lymphocyte Proliferation Response to Pollen Extract as a Monitor of Immunotherapy
Authors: Christian Möller, Per Juto, Sten Dreborg, Bengt Björkstén
Journal: Allergy (1984)

In a study of immunotherapy 41 children with seasonal rhinoconjunctivitis due to deciduous tree pollen allergy were monitored by means of symptom scoring, patient self‐evaluation, conjunctival provocation tests and lymphocyte proliferation in vitro to the allergen. The lymphocyte responsiveness to birch pollen decreased significantly during the first year of immunotherapy. However, neither the lymphocyte responsiveness before treatment nor changes in lymphocyte reactivity during the immunotherapy correlated with the clinical efficacy of the therapy as evaluated by changes in symptom scores, self‐evaluation or conjunctival provocation test changes in the individual patients. The results indicate the lymphocyte responsiveness to an allergen cannot be used to select patients for immunotherapy, i.e. to predict whether a patient would benefit from immunotherapy or not, or to evaluate the effects of immunotherapy after beginning the treatment. However, lymphocyte proliferation response to an allergen indicates clinical sensitivity.
Cause and outcome of atypical chest pain in patients admitted to hospital
Authors: L. Spalding, E. Reay, C. Kelly
Journal: Journal of the Royal Society of Medicine (2003)

In patients with acute chest pain the prime need, usually, is to diagnose and treat myocardial infarction or ischaemia. When a cardiac origin for the pain has been excluded, patients are commonly discharged without either a diagnosis or a plan for follow-up. We studied a group of such patients to see how far causation was pursued and how their mortality compared with that of patients with a proven cardiac cause for their symptoms. The study population was 250 patients admitted over five weeks with chest pain suspected of being cardiac in origin. Initial assessment included an electrocardiogram and measurement of troponin T. If neither of these indicated a cardiac event, the patient was deemed to have 'atypical' chest pain and the cause, where defined, was recorded. Outcomes at one year were determined by questionnaire and by assessment of medical notes. Of the 250 patients, 142 had cardiac pain (mean age 79 years, 58% male) and 108 atypical chest pain (mean age 60 years, 55% male). Of those with atypical pain, 40 were discharged without a diagnosis; in the remaining 68 the pain was thought to be musculoskeletal (25), cardiac (21), gastrointestinal (12) or respiratory (10) in origin. 41 patients were given a follow-up appointment on discharge. At one year, data were available on 103 (96%) patients. The mortality rate was 2.9% (3 patients) compared with 18.3% in those with an original cardiac event. Half of the patients with atypical pain had undergone further investigations and 14% had been readmitted. The yield of investigative procedures was generally low (20%) but at the end of the year only 27 patients remained undiagnosed. Patients with atypical chest pain form a substantial proportion of emergency admissions. The symptoms often persist or recur. The commonest causation is musculoskeletal, but a sizeable minority remain undiagnosed even after follow-up.
New Proposal for Postsurgery Pathologic Staging of Esophageal or Gastroesophageal Junction Adenocarcinoma: Why Bother?
Authors: Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2007)

TO THE EDITOR: Lagarde et al 1 should be commended for an extensive and painstaking review of the prognostic factors of esophageal or gastroesosphageal adenocarcinoma. Their article serves as a useful reference for those interested in this disease process. They point out that the current classification of these tumorsisoutdated.Foralongtime,variousgroupshaveexpressed considerable dissatisfaction with the current staging system. A variety of modifications have been proposed, but no group has provided a solution that is acceptable to all others. The authors haveveryclearlypointedoutthatsurgeryasprimarytherapy(most frequently diagnosed cancer is stage II or III) results in a dismal outcome ( 25% 5-year survival rate) and the results of randomized trials of preoperative chemoradiotherapy trials have been equivocal. The goal of preoperative chemoradiotherapy is not just to improve local control, but all such trials strived to improve overallsurvival(theprimaryendpoint)ofthepatients.Contraryto the authors’ assertion that response to preoperative chemoradiotherapy has a minor prognostic impact on prognosis, the pathologicstageafterpreoperativechemoradiotherapyremainsthemost importantindependentprognosticfactorinamultivariateanalysis of patients undergoing preoperative chemoradiotherapy 2 and similar findings have been reported by other major institutions. 3,4 The authors do not point out that clinical stage (cT or cN) does not predict patient outcome whether surgery is used as primary therapy or not and certainly not in the setting of preoperative chemoradiotherapy. 2-4 The authors go on to propose that a sophisticated postoperative staging system for localized esophageal and gastroesophageal junctionadenocarcinomashouldbedeveloped.Suchanewsystem may be of some academic interest, however, its value should be questioned, particularly when we consider the future approaches to improve the outcome of such patients. Should we continue to offer surgery as the primary therapy for clinical stage II or III esophageal or gastroesophageal junction cancer? No, not based on the utterly disappointing results. The 5-year survival rate of patients with postsurgery pathologic stage IIA after surgery as primarytherapyislessthan35%andthosewithanystagehigherthan IIA results in a less than 20% 5-year survival rate. 5 What is to be accomplished by a new staging system with such poor results? The future improvements in the outcome are hardly likely from subjectingmoreandmorepatientswithstageIIorIIIcancertosurgery first and developing a new postsurgery pathologic classification, as proposed. That would be just too simplistic and without considerationstofailureofthecurrentapproachesinpatientswithlocalized
Serum Interleukin-7 (IL-7) Level May Be a Marker of T-Cell Homeostasis in Partial DiGeorge Syndrome (pDGS)
Authors: U. Tantibhaedhyangkul, C.M. Davis, L.M. Noroski, I.C. Hanson, W.T. Shearer, J. Chinen
Journal: Journal of Allergy and Clinical Immunology (2009)
Neutrophilic Dermatosis After Azathioprine Exposure
Authors: Nika Cyrus, Robert Stavert, Ashley R. Mason, Christine J. Ko, Jennifer Nam Choi
Journal: JAMA Dermatology (2013)

<h3>Importance</h3>Azathioprine hypersensitivity syndrome can present clinically and histopathologically like Sweet syndrome. Shared clinical features include fever, constitutional symptoms, prompt response to systemic corticosteroid therapy, neutrophilia, and abrupt onset of erythematous cutaneous lesions. Histologically, both azathioprine hypersensitivity syndrome and Sweet syndrome are rich in neutrophils.<h3>Observations</h3>An 81-year-old woman with Crohn disease presented with fever and an acute eruption of plaques on her extremities within 2 weeks of starting treatment with azathioprine. Laboratory evaluation was notable for leukocytosis and neutrophilia. Skin biopsy of an erythematous plaque on the thigh demonstrated a suppurative folliculitis. Azathioprine treatment was discontinued resulting in resolution of the clinical lesions within 5 days. Our case was compared with 18 cases with similar clinical features.<h3>Conclusions and Relevance</h3>We report a case of azathioprine hypersensitivity syndrome and review the literature on azathioprine-induced eruptions with features of Sweet syndrome. Our patient's distribution of lesions on the extremities and the finding of suppurative folliculitis on histopathology were not classical for Sweet syndrome. Azathioprine hypersensitivity syndrome seems to be a neutrophil-driven dermatosis; therefore, many overlapping features with Sweet syndrome are not surprising. Due to the potential for anaphylaxis with azathioprine rechallenge, a better term for a Sweetlike presentation in the setting of azathioprine administration is azathioprine hypersensitivity syndrome.