tbuckley/cabot-search huggingface dataset:
Adrenomedullin, endothelin, neuropeptide Y, atrial, brain, and C-natriuretic prohormone peptides compared as early heart failure indicators1
Authors: Sreedevi Daggubati, James R Parks, Rose M Overton, Guillermo Cintron, Douglas D Schocken, David L Vesely
Journal: Cardiovascular Research (1997)

Objectives: The present investigation was designed to determine the best endogenous plasma marker of early congestive heart failure (CHF). Methods: Forty volunteers with mild CHF (New York Heart Association Class I, n = 12), moderate (Class II, n = 8), or severe (Class III and Class IV, each=n of 5) and 10 age-matched healthy individuals had the simultaneous evaluation of their respective plasma samples by the following radioimmunoassays: atrial natriuretic peptide, ANP; three N-terminal ANP prohormone assays, i.e., proANPs 1–30, 31–67, and 79–98 with the numbers referring to their amino acid (a.a.) sequences in their 126 a.a. prohormone; brain (BNP) and C-natriuretic peptides; N-terminal BNP prohormone; adrenomedullin; neuropeptide Y and endothelin. Results: ProANPs 31–67, 1–30 and 79–98 had 100% (P = 0.01), 83% (P = 0.09) and 50% (P = 0.74) sensitivity in differentiating Class I CHF subjects from healthy subjects. The ANP, BNP, NT-proBNP, CNP, adrenomedullin, neuropeptide Y, and endothelin assays could not differentiate mild CHF subjects from healthy individuals. Logistic regression analysis revealed that only proANP 31–67 significantly (P = 0.0001) discriminated between early CHF (5226±377 pg/ml) and healthy individuals (1595±157 pg/ml). The positive and negative predictive values of proANP 31–67 were excellent (100% for each). The peptides measured in these assays were found to be independent markers of CHF with respect to left ventricular ejection fraction. Conclusions: ProANPs 31–67 is the most sensitive marker in discriminating NYHA Class I CHF subjects from healthy individuals. The ANP, BNP, NT-proBNP, CNP, adrenomedullin, neuropeptide Y and endothelin radioimmunoassays cannot discern mild CHF. These peptides are independent of left ventricular ejection fraction.
Diastolic anisotropic properties of the left ventricle in the conscious dog.
Authors: C O Olsen, D D Glower, K L Lee, P A McHale, J S Rankin
Journal: Circulation Research (1991)

The role of myocardial anisotropy in determining change in left ventricular shape during diastolic filling has not yet been demonstrated. Therefore, 11 conscious dogs were instrumented with global ultrasonic dimension transducers to measure left ventricular major and minor axis diameters and equatorial wall thickness. Myocardial geometry was represented as a three-dimensional ellipsoidal shell. Left ventricular transmural pressure was measured with micromanometers, and ventricular volume was varied by inflation of vena caval occluders. Left ventricular wall strains and stresses calculated from the ellipsoidal shell model agreed closely with those measured directly by myocardial force and dimension transducers. Unequal normalized diastolic stress-strain relations were observed in the latitudinal, longitudinal, and wall thickness directions, reflecting anisotropic mechanical properties of the myocardium. Although a greater wall stress in the latitudinal versus longitudinal axis was predicted adequately from left ventricular geometry alone, the observed latitudinal strain exceeded longitudinal strain by an amount greater than was predicted by geometric considerations alone, suggesting that myocardial anisotropy contributes significantly to changes in ventricular shape during diastolic filling.
Identification of a Pre-BCR Lacking Surrogate Light Chain
Authors: Yu-wen Su, Alexandra Flemming, Thomas Wossning, Elias Hobeika, Michael Reth, Hassan Jumaa
Journal: The Journal of Experimental Medicine (2003)

SLP-65−/− pre-B cells show a high proliferation rate in vitro. We have shown previously that λ5 expression and consequently a conventional pre-B cell receptor (pre-BCR) are essential for this proliferation. Here, we show that pre-B cells express a novel receptor complex that contains a μ heavy chain (μHC) but lacks any surrogate (SL) or conventional light chain (LC). This SL-deficient pre-BCR (SL−pre-BCR) requires Ig-α for expression on the cell surface. Anti-μ treatment of pre-B cells expressing the SL−pre-BCR induces tyrosine phosphorylation of substrate proteins and a strong calcium (Ca2+) release. Further, the expression of the SL−pre-BCR is associated with a high differentiation rate toward κLC-positive cells. Given that B cell development is only partially blocked and allelic exclusion is unaffected in SL-deficient mice, we propose that the SL−pre-BCR is involved in these processes and therefore shares important functions with the conventional pre-BCR.
Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis
Authors: Jan Hellemans, Olena Preobrazhenska, Andy Willaert, Philippe Debeer, Peter C M Verdonk, Teresa Costa, Katrien Janssens, Bjorn Menten, Nadine Van Roy, Stefan J T Vermeulen, Ravi Savarirayan, Wim Van Hul, Filip Vanhoenacker, Danny Huylebroeck, Anne De Paepe, Jean-Marie Naeyaert, Jo Vandesompele, Frank Speleman, Kristin Verschueren, Paul J Coucke, Geert R Mortier
Journal: Nature Genetics (2004)
THE OCCURRENCE OF TWO M ANTIGENS IN CERTAIN GROUP A STREPTOCOCCI RELATED TO TYPE 14
Authors: Grove G. Wiley, Armine T. Wilson
Journal: The Journal of Experimental Medicine (1961)

A strain of Group A streptococcus previously considered to belong to Type 14 was shown to have two immunologically distinct M antigens, designated Type 14 and Type 51. Most strains having the Type 14 M antigen were found to have also the Type 51 M antigen, and are considered to belong to Type 14-51. Four strains had the Type 51 M antigen without the Type 14 M antigen and one strain had the Type 14 M antigen without the Type 51 M antigen. The failure of a variant to produce the known M antigen of the parent strain does not necessarily mean that the strain is M(-), because a second M antigen may be present as was the case in several strains described here.
Genetics of Essential Hypertension
Authors: Cristina Barlassina, Chiara Lanzani, Paolo Manunta, Giuseppe Bianchi
Journal: Journal of the American Society of Nephrology (2002)

Family studies demonstrated the contribution of genetic factors to the development of primary hypertension. However, the transition from this phenomenologic-biometric approach to the molecular-genetic one is more difficult. This last approach is mainly based on the Mendel paradigm; that is, the dissection of the poligenic complexity of hypertension is brought about on the assumption that the individual genetic variants underlying the development of hypertension must be more frequent in hypertensive patients than in controls and must cosegregate with hypertension in families. The validity of these assumptions was clearly demonstrated in the so-called monogenic form of hypertension. However, because of the network of the feedback mechanisms regulating BP, it is possible that that the same gene variant may have an opposite effect on BP according to the genetic and environmental backgrounds. Independent groups of observations (acute BP response to saline infusion, incidence of hypertension in a population follow-up of 9 yr, age-related changes on BP) discussed in this review suggest a positive answer to this question. Therefore the impact of a given genetic variant on BP level must be evaluated within the context of the appropriate genetic epistatic interactions. A negative finding or a minor genetic effect in a general population may become a major gene effect in a subset of people with the appropriate genetic and environmental backgrounds.
Differential DNA Methylation In Mothers Increases The Prevalence Of Atopic Dermatitis In Their Offspring
Authors: Pia J. Hauk, Anna Forssen, Brent Pedersen, Matthew Strand, Lindsay Munoz, Michaela Schedel, Anne Lynch, Virginia Winn, David A. Schwartz, Erwin W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2014)
Habitual physical activity in cystic fibrosis
Authors: Daniela Savi, Mattia Internullo, Giuseppe Cimino, Elena Angelici, Serena Quattrucci, Patrizia Troiani, Salvatore Cucchiara, Paolo Palange
Journal: European Respiratory Journal (2012)

Introduction. Habitual physical activity has important clinical implications in Cystic Fibrosis (CF) and has therapeutic effects on sputum clearance, respiratory muscle strength and quality of life. While recent studies have shown that aerobic fitness is related to survival, that physically active CF patients have higher peak oxygen uptake (VO2peak) and lower rate of decline of FEV1, less is known about the relationship between physical activity levels and patients9s functional status, including exercise tolerance. Methods. Eleven stable CF patients (mean (SD) age 32 (9) yrs; FEV1 2.7 (0.8) l; IC 3.8 (0.9) l), were studied at rest, during symptom-limited incremental exercise test (CPET) and during 6MWT. We assessed daily physical activity using both SW (SenseWear, SW) that subjects wore for 4 consecutive days from waking until going to bed including weekends, and the Habitual Activity Estimation Scale Questionnaire (HAESQ). Results. There was no difference between the weekdays and weekends recordings in any activity variable. We found no agreement in physical activity measured by SW vs HAESQ. By contrast, we found a close relationship between SW step count and FEV1 (r2=0.9; p
No Need for the Needle (at First)
Authors: Mayer B. Davidson
Journal: Diabetes Care (2008)

In this issue of Diabetes Care , Chen et al. (1) describe an approach to the initial treatment of newly diagnosed type 2 diabetic patients with severe hyperglycemia (fasting plasma glucose [FPG] concentrations >300 mg/dl or random plasma glucose concentrations >400 mg/dl) entailing intensive insulin therapy during 10 to 14 days of hospitalization. Following this, half of the patients were randomized to continued insulin treatment and the other half to oral antidiabetes drugs (OAD), starting with metformin in overweight and obese patients and a sulfonylurea (SU), gliclazide, in lean patients. If satisfactory control was not obtained with a single OAD, a combination of metformin and the SU was used. Doses of insulin and the OAD were adjusted at each outpatient visit every 2 weeks during the first 2 months and every 4 weeks for another 4 months. Oral glucose tolerance tests were performed after the intensive insulin therapy: once just before randomization and again 6 months later. At that time, patients in the insulin group were switched to OAD and all patients were followed for another 6 months.

As expected, FPG concentrations were no different at randomization: however, they were significantly increased in the OAD group compared with those maintained on insulin. A1C levels were significantly lower at 3 and 6 months in patients maintained on insulin compared with those given OAD. They also remained significantly lower 6 months after the insulin patients were switched to OAD.

Glucose and insulin responses among the insulin and OAD groups to the …
MiR-23a-mediated inhibition of topoisomerase 1 expression potentiates cell response to etoposide in human hepatocellular carcinoma
Authors: Ning Wang, Meifen Zhu, Sai-Wah Tsao, Kwan Man, Zhangjin Zhang, Yibin Feng
Journal: Molecular Cancer (2013)

Abstract Background microRNAs have been shown to regulate the chemosensitivity of cancer cells. The aim of this study is to investigate the role and mechanism of mir-23a in enhancing the anti-tumor effect of topoisomerase 2A (TOP2A) poison etoposide in human hepatocellular carcinoma (HCC). Methods The anti-tumor effect of chemotherapeutic agents in HCC cells were examined in vitro and in vivo xenograft model. Expression of mRNA and miRNAs were determined by quantitative real-time PCR. Protein expression was analyzed by immunoblotting. Results Overexpression of mir-23a could significantly potentiate the in vitro and in vivo anti-tumor effect of etoposide; however, ectopic expression of miR-23a fails to sensitize HCC cells to 5-fluorouracil treatment, indicating the miR-23a-induced cancer cell hypersensitivity in chemotherapy is TOP2A-specific though miR-23a overexpression could not directly up-regulate TOP2A expression. Topoisomerase 1(TOP1) is down-regulated in miR-23a-overexpressed HCC cells. MiR-23a could directly bind to 3′untranslated region of TOP1 mRNA, and suppress the corresponding protein expression and inhibition of miR-23a further arguments the expression of TOP1. MiR-23a was up-regulated during DNA damage in cancer cells in line with the p53 expression. Up-regulation of p53 induces mir-23a expression, while suppression of p53 inhibits miR-23a in HCC cells. Conclusion Our study sheds light on the role of miR-23a as a potential target in regulating chemosensitivity of HCC cells.
TCTAP A-008 Preventive Versus Culprit-only Percutaneous Coronary Intervention in ST-elevation Myocardial Infarction Patients with Multivessel Disease: A Meta-Analysis
Authors: Yeo-Jeong Song, Jae-Sik Jang, Joo-Il Yang, Ho-Young Lee, Han-Young Jin, Jeong-Sook Seo, Tae-Hyun Yang, Dae-Kyeong Kim, Dong-Soo Kim
Journal: Journal of the American College of Cardiology (2014)
Evaluation of Bipolar Disorder in Inpatients With Prelingual Deafness
Authors: Nathan A. Shapira, Melissa P. DelBello, Toby D. Goldsmith, Betty M. Rosenberger, Paul E. Keck
Journal: American Journal of Psychiatry (1999)

This study retrospectively examined the occurrence of bipolar disorder in patients with prelingual deafness who were hospitalized for a psychiatric disorder.The hospital charts since 1983 of all psychiatrically admitted deaf patients were retrospectively evaluated for diagnoses by using DSM-IV criteria. Those with a best-estimate diagnosis of bipolar disorder were compared to those with other diagnoses.There were 28 patients with prelingual deafness who had at least one psychiatric diagnosis from 1983 to 1998. Upon chart review, 11 (39.3%) were diagnosed with bipolar disorder. Patients with bipolar disorder and deafness had rates of inaccurate discharge diagnoses that were similar to those of other deaf patients (70.8% versus 56.7%).Bipolar disorder may be more common in inpatients with prelingual deafness than has been previously described in the literature. Further research regarding the sources contributing to misdiagnosis of psychiatric disorders in this population is warranted.
The sequence of retrograde atrial activation in the canine heart. Correlation with positive and negative retrograde P waves.
Authors: A L Waldo, K J Vitikainen, B F Hoffman
Journal: Circulation Research (1975)

The relationship of P-wave polarity and morphology in leads II, III, and aVF to the sequence of atrial activation was studied in the canine heart when the atria were paced from the region of the sinus node or the posterior-inferior left atrium and when retrograde activation of the atria occurred with right ventricular epicardial pacing. Deeply negative P waves in leads II, III, and aVF which occurred when the posterior-inferior left atrium was paced were associated with true retrograde activation of the atria. Positive P waves recorded in leads II, III, and aVF during retrograde atrial capture with right ventricular pacing were associated with rapid retrograde spread of the impulse in the interatrial septum to the region of Bachmann's bundle from which site the impulse spread to depolarize significant portions of both atria in a manner similar to that demonstrated during pacing from the region of the sinus node. When the atria were paced from a site just anterior to the coronary sinus ostium, positive P waves recorded in leads II, III, and aVF were associated with early activation in the vicinity of Bachmann's bundle and later activation of the posterior-inferior left atrium. When the atria were paced from a site just posterior to the coronary sinus ostium, negative P waves in leads II, III, and aVF were associated with early activation of the posterior-inferior left atrium and later activation in the vicinity of Bachmann's bundle. It was concluded that the time of arrival of the impulse at Bachmann's bundle relative to that at the posterior left atrium and the direction of spread of the impulse from and within Bachmann's bundle are critical in determining P-wave polarity and morphology.
Effect of the C3435T genetic polymorphism in MDR1 on etoposide pharmacokinetics
Authors: R. M. Strother, D. Jones, L. Li, A. Younger, L. H. Einhorn, S. Williams, C. J. Sweeney
Journal: Journal of Clinical Oncology (2008)

2500 Background: Etoposide, a podophylotoxin-derived topoisomerase II inhibitor has pharmacokinetics (PK) which exhibit wide interpatient variability. The present study explores the effect of polymorphisms in the xenobiotic transporter, multi-drug resistance-1 (MDR-1), on etoposide PK. Previous in vitro work has shown MDR-1 levels effect efflux of etoposide. Methods: The PK profile of etoposide was determined from 15 patients treated with 100 mg/m2 as a 1 hour intravenous infusion in combination with cisplatin and bleomycin. Genomic DNA was extracted from whole blood. Samples were analyzed for MDR1 2677G/T/A and 3435C/T. Blood samples following dosing on day 1 of any of 3 cycles were obtained at 10, 15, 30, 45 minutes and 2, 3, 6.5, 8, 12, and 24 hours following end of infusion. Etoposide concentrations were determined on an HPLC-MS/MS with teniposide as internal standard. Individual pharmacokinetic analysis was performed on WinNonLin (Pharsight). Population pharmacokinetics was performed on WinNonMix (Pharsight). Statistical analysis was performed on SPSS, with ANOVA for covariates. Results: Data was fit to a 2-compartment model, giving population mean volume of distribution of 5.63 L (CV 34.5%) and clearance of 0.96 L/hr (CV 28.2%), which is consistent with prior reports of these parameters. 14 subjects had specimens available for genotyping. Subjects showed the following distributions for MDR1 2677 and 3435, respectively: 1 AT, 2 TT, 8 TG, and 3 GG; 1 CC, 9 TC, and 4 TT. MDR1 3435TT was associated with lower volume of distribution (L) of etoposide (ANOVA p =0.034) - CC - 10.62; TC - 5.47; TT - 4.72. There were no statistically significant associations between cycle, dose, or MDR1 2677G/T/A. Conclusions: MDR1 3435 TT genotype is associated with lower volume of distribution and contributes significantly to the interindividual variability observed in etoposide pharmacokinetics. This is consistent with previous work which has shown the TT genotype is associated with changes in etoposide pharmacokinetic parameters which showed an association between clearance and genotype in a prednisone-induced setting in a pediatric population. Protocol supported by Lance Armstrong Foundation. No significant financial relationships to disclose.
Nocturnal Hemodialysis Improves Erythropoietin Responsiveness and Growth of Hematopoietic Stem Cells
Authors: Christopher T. Chan, Peter P. Liu, Sara Arab, Nazir Jamal, Hans A Messner
Journal: Journal of the American Society of Nephrology (2008)

Nocturnal home hemodialysis (NHD) is associated with an increase in hemoglobin level. We hypothesized that NHD enhances the removal of toxins of hematopoietic progenitor cells (HPCs), thereby improving HPC growth and function. Among 16 patients with ESRD, 2 mo of NHD nearly doubled Kt/V per session and significantly lowered both parathyroid hormone levels and serum phosphate concentration. In addition, treatment with NHD improved hemoglobin levels from 113 +/- 3 to 125 +/- 4 g/L (P = 0.03) without altering erythropoietin requirements or iron status. To assess whether NHD may enhance removal of HPC toxins, we collected paired plasma samples from the same patient during treatment with conventional HD and NHD. In vitro, growth of erythroid (BFU-E) and granulocytic (CFU-GM) colonies was superior when cultured with NHD plasma compared with conventional HD plasma. Differential gene expression profiles obtained from peripheral blood and HPC colonies revealed similar upregulation of genes responsible for HPC mobilization and growth and production of red blood cells. In conclusion, the enhanced clearance by NHD is associated with an improvement in HPC growth and a coordinated increase in expression of genes relevant to production of red blood cells.
Abstract 20004: Long-term Risk of Mortality, Aortic Dissection and Thoracic Aortic Surgery After Isolated Aortic Valve Replacement in Patients With Bicuspid and Tricuspid Aortic Valves
Authors: Shinobu Itagaki, Yuting Chiang, Joanna Chikwe
Journal: Circulation (2014)

Introduction: The natural history of aortopathy after isolated aortic valve replacement (AVR) in patients with bicuspid aortic valves (BAV) is not well characterized. Hypothesis: The incidence of dissection and thoracic aortic surgery after isolated AVR in patients with BAV is higher than in patients with tricuspid valves. Methods: From 1995-2010, 2,203 bicuspid and 1,436 rheumatic tricuspid patients undergoing isolated AVR were identified from the Statewide Planning and Research Cooperative System which captures all inpatient admissions and emergency visits to every hospital in New York State. Deaths were identified from the Social Security Death Master File. Kaplan-Meier analysis of survival and competing risk analysis of aortic dissection and thoracic aortic surgery was performed. Results: BAV patients were younger than tricuspid aortic valve (TAV) patients (52.0 vs. 64.2 years, p&lt;0.001). Survival at 15 years after AVR was 77% versus 58%, respectively (p&lt;0.001). During median follow up of 8.0 years (range 0-19.0 years), aortic dissection occurred in 9 BAV patients versus 4 TAV patients. The 15-year cumulative incidence of dissection after AVR in BAV patients was 0.7% versus 0.4% in TAV patients (p=0.28) (Figure 1). Thoracic aortic surgery was performed in 33 BAV patients versus 9 TAV patients. The 15-year cumulative incidence of thoracic aortic surgery was 3.1% in BAV patients versus 1.1% in TAV patients (p&lt;0.001) (Figure 2). Conclusions: Patients undergoing isolated AVR of bicuspid valves are at greater long-term risk of aortic dissection and thoracic aortic surgery than patients with tricuspid valves, and should be considered for life-long surveillance.
Unspecific binding of group B streptococcal cocytolysin (CAMP factor) to immunoglobulins and its possible role in pathogenicity.
Authors: D Jürgens, B Sterzik, F J Fehrenbach
Journal: The Journal of Experimental Medicine (1987)

The protein B of group B streptococci can bind in a nonimmune reaction to Ig of the IgG and IgM classes of various mammalian species (i.e., human, mouse, rabbit, and bovine). Protein B binding involves the Fc parts of both IgG and IgM molecules. Monoclonal or polyclonal IgG or IgM and the IgM-FC5 mu fragment of human myeloma protein combined with the protein B thereby inhibiting protein B-induced hemolysis in the CAMP reaction. The protein B/Ig complex can be dissociated with 1% Triton or guanidine-HCl (6 M). Mice infected intraperitoneally with sublethal doses of group B streptococci (GBS) and that received seven repeated intravenous injections of highly purified protein B during the first 9 h of infection developed fatal septicemia within 24 h with colony counts of up to 10(8) CFU/ml in the blood. Animals treated in the same way with either PBS or trypsinized protein B recovered. The protein B itself was not pathogenic when injected into healthy mice. Tissue sections of liver or spleen from mice infected with a lethal dose of GBS revealed the presence of protein B together with large numbers of cocci when stained by the peroxidase method using specific antibodies raised against purified protein B in the rabbit.