tbuckley/cabot-search huggingface dataset:
LEUCOPROTEASE AND ANTI-LEUCOPROTEASE OF MAMMALS AND OF BIRDS
Authors: Eugene L. Opie, Bertha I. Barker
Journal: The Journal of Experimental Medicine (1907)

The inhibiting action of the blood serum upon the enzyme of the polynuclear leucocytes, leucoprotease, is exerted by the albumin fraction of the serum. The albumin fraction contains no proteolytic enzymes. The globulin fraction of the serum contains no anti-enzyme for leucoprotease; it contains, on the contrary, an enzyme which digests proteids in a neutral or alkaline medium. This enzyme resembles leucoprotease which is present in the polynuclear leucocytes of an inflammatory exudate and in the bone marrow from which these cells are derived, and is doubtless identical with the similar enzyme occurring in smaller quantity in the spleen. This enzyme which is present in the blood serum is held in check by its anti-enzyme, but the latter is in such excess that the serum as a whole is capable of checking the action of leucoprotease when added in considerable quantity. Leucoprotease of one mammalian species is inhibited by sera of other mammalian species, but the anti-enzymotic activity of various sera differs; the anti-enzyme of the rabbit's serum is stronger than that of dog's serum, when tested either with dog's or with rabbit's leucoprotease. The co-existence in the rabbit of leucoprotease with feeble strength and anti-body of great activity may explain the absence in these animals of typical suppuration with liquefaction of tissues. The serum of birds which have been tested, namely, pigeon and hen, almost completely fails to inhibit mammalian leucoprotease (of dog). The polynuclear leucocytes, the bone marrow and the spleen of the hen do not contain an enzyme resembling leucoprotease of mammals. The absence of anti-enzyme in the serum is associated with absence of a corresponding enzyme in the leucocytes.
Sculpting Organs: Mechanical Regulation of Tissue Development
Authors: Celeste M. Nelson, Jason P. Gleghorn
Journal: Annual Review of Biomedical Engineering (2012)

The ramified architectures of organs such as the mammary gland and lung are generated via branching morphogenesis, a developmental process through which individual cells bud and pinch off of pre-existing epithelial sheets. Although specified by signaling programs, organ development requires integration of all aspects of the microenvironment. We describe the essential role of endogenous cellular contractility in the formation of branching tubes. We also highlight the role of exogenous forces in normal and aberrant branching.
Quantitative Analysis of the Development of Experimental Atherosclerosis in the Dog
Authors: LEROY E. DUNCAN, KATHERIN BUCK, Almorris Lynch
Journal: Circulation Research (1960)

Atherosclerosis was produced in dogs by feeding them thiouracil and cholesterol. The increments in cholesterol concentration at sites along the length of the aortas of these dogs Avere determined by subtracting from the value for each site the corresponding value obtained from normal dogs. After about 1 month on the experimental regimen the cholesterol increments along the length of the aorta formed a gradient. The increment was greatest in the proximal aorta and progressively less down the length of the aorta. After about 5 months on the regimen, the gradient no longer existed. Instead, the cholesterol increment in the abdominal aorta exceeded that in the thoracic aorta. Albumin is known to enter aortic wall with a gradient of rates that is similar to the gradient of cholesterol increments early in the course of experimental atherosclerosis. The foregoing facts are consistent with the following theory: In the development of atherosclerosis, intact low-density lipoproteins containing cholesterol enter the aortic wall with a gradient of rates. They enter fastest in the proximal aorta and progressively less rapidly down the length of the aorta. However, cholesterol is removed from the abdominal aorta much more slowly than from the thoracic aorta. Thus, the increment in cholesterol concentration in the abdominal aorta eventually exceeds that in the thoracic aorta.
Thrombocytosis: Misdiagnosis and its prevention
Authors: Tikva Yermiahu, Hana Shalev, Lev Hatskelzon
Journal: American Journal of Hematology (1995)

PB findings Schisto microsp Hb-H P Schisto microsp Hb-H P Schisto microsp Hb-H P Schisto microsp Hb-H P Schisto microsp Hb-H P s/c/p .-*MDS = myelodisplastic syndrome; Schisto = schistocytes; microsp = microapherocytes; skip = smudge cell particle; Hb-H P = disintegrated Hh
RESPONSE: Re: Serum Proteomic Patterns for Detection of Prostate Cancer
Authors: E. F. Petricoin, L. A. Liotta
Journal: JNCI Journal of the National Cancer Institute (2003)

Petricoin et al.(1) proposed that assessment of serum proteomic patterns with mass spectrometry and combination of these patterns with a bioinformatic algorithm can detect prostate cancer with approximately 95% sensitivity and 70%-80% specificity.These figures seem favorable when compared with common biochemical testing for prostate cancer, which currently includes analysis of total prostate-specific antigen (PSA) and percent free PSA in serum.Similar approaches have been proposed by the same group for the diagnosis of ovarian and other cancers (2).The authors speculate that the discriminatory proteomic patterns originate from proteins (including cytokines, chemokines, metabolites, or enzymatic cleavage products) released by the prostate or its microenvironment during blood percolation through the organ.However, a limitation of this technology, also discussed elsewhere (3), is that the authors offer no evidence in regard to the identity of their seven most discriminatory molecules.In a previous publication (4), the authors contend that the identity of these proteins is not important in the context of their method.However, the identity of such proteins, as well as their relative concentrations in serum, is of paramount importance for understanding why they offer discriminatory power for detecting prostate cancer and how they originated in the circulation.For example, to derive their algorithm, Petricoin et al. (1) used serum samples from patients with biopsyproven prostate cancer and total PSA levels of more than 4 ng/mL and from patients with no evidence of disease and total PSA levels of less than 1 ng/mL.It would have been interesting to know whether the authors' method identified this internal control and highly discriminating molecule (i.e., PSA) as one of the discriminatory proteins in serum.Such a finding would confirm that their method is sensitive enough to detect proteins at a concentration level of 1 ng/mL or higher.Their method of extracting serum prior to analysis (i.e., by hydrophobic interaction with a C16 column),
Population Bottlenecks and Pleistocene Human Evolution
Authors: J Hawks, K Hunley, S H Lee, M Wolpoff
Journal: Molecular Biology and Evolution (2000)

We review the anatomical and archaeological evidence for an early population bottleneck in humans and bracket the time when it could have occurred. We outline the subsequent demographic changes that the archaeological evidence of range expansions and contractions address, and we examine how inbreeding effective population size provides an alternative view of past population size change. This addresses the question of other, more recent, population size bottlenecks, and we review nonrecombining and recombining genetic systems that may reflect them. We examine how these genetic data constrain the possibility of significant population size bottlenecks (i.e., of sufficiently small size and/or long duration to minimize genetic variation in autosomal and haploid systems) at several different critical times in human history. Different constraints appear in nonrecombining and recombining systems, and among the autosomal loci most are incompatible with any Pleistocene population size expansions. Microsatellite data seem to show Pleistocene population size expansions, but in aggregate they are difficult to interpret because different microsatellite studies do not show the same expansion. The archaeological data are only compatible with a few of these analyses, most prominently with data from Alu elements, and we use these facts to question whether the view of the past from analysis of inbreeding effective population size is valid. Finally, we examine the issue of whether inbreeding effective population size provides any reasonable measure of the actual past size of the human species. We contend that if the evidence of a population size bottleneck early in the evolution of our lineage is accepted, most genetic data either lack the resolution to address subsequent changes in the human population or do not meet the assumptions required to do so validly. It is our conclusion that, at the moment, genetic data cannot disprove a simple model of exponential population growth following a bottleneck 2 MYA at the origin of our lineage and extending through the Pleistocene. Archaeological and paleontological data indicate that this model is too oversimplified to be an accurate reflection of detailed population history, and therefore we find that genetic data lack the resolution to validly reflect many details of Pleistocene human population change. However, there is one detail that these data are sufficient to address. Both genetic and anthropological data are incompatible with the hypothesis of a recent population size bottleneck. Such an event would be expected to leave a significant mark across numerous genetic loci and observable anatomical traits, but while some subsets of data are compatible with a recent population size bottleneck, there is no consistently expressed effect that can be found across the range where it should appear, and this absence disproves the hypothesis.
Risks of Complications by Attending Physicians After Performing Nighttime Procedures
Authors: Jeffrey M. Rothschild
Journal: JAMA (2009)

Few data exist on the relationships between experienced physicians' work hours and sleep, and patient safety.To determine if sleep opportunities for attending surgeons and obstetricians/gynecologists are associated with the risk of complications.Matched retrospective cohort study of procedures performed from January 1999 through June 2008 by attending physicians (86 surgeons and 134 obstetricians/gynecologists) who had been in the hospital performing another procedure involving adult patients for at least part of the preceding night (12 am-6 am, postnighttime procedures). Sleep opportunity was calculated as the time between end of the overnight procedure and start of the first procedure the following day. Matched control procedures included as many as 5 procedures of the same type performed by the same physician on days without preceding overnight procedures. Complications were identified and classified by a blinded 3-step process that included administrative screening, medical record reviews, and clinician ratings.Rates of complications in postnighttime procedures as compared with controls; rates of complications in postnighttime procedures among physicians with more than 6-hour sleep opportunities vs those with sleep opportunities of 6 hours or less.A total of 919 surgical and 957 obstetrical postnighttime procedures were matched with 3552 and 3945 control procedures, respectively. Complications occurred in 101 postnighttime procedures (5.4%) and 365 control procedures (4.9%) (odds ratio, 1.09; 95% confidence interval [CI], 0.84-1.41). Complications occurred in 82 of 1317 postnighttime procedures with sleep opportunities of 6 hours or less (6.2%) vs 19 of 559 postnighttime procedures with sleep opportunities of more than 6 hours (3.4%) (odds ratio, 1.72; 95% CI, 1.02-2.89). Postnighttime procedures completed after working more than 12 hours (n = 958) compared with 12 hours or less (n = 918) had nonsignificantly higher complication rates (6.5% vs 4.3%; odds ratio, 1.47; 95% CI, 0.96-2.27).Overall, procedures performed the day after attending physicians worked overnight were not associated with significantly increased complication rates, although there was an increased rate of complications among postnighttime surgical procedures performed by physicians with sleep opportunities of less than 6 hours.
Hepatitis B Virus Large Surface Antigen Promotes Liver Carcinogenesis by Activating the Src/PI3K/Akt Pathway
Authors: Haiou Liu, Jiejie Xu, Lei Zhou, Xiaojing Yun, Lin Chen, Shanshan Wang, Linlin Sun, Yumei Wen, Jianxin Gu
Journal: Cancer Research (2011)

Of the three envelope glycoproteins encoded by hepatitis B virus (HBV) that are collectively referred to as HBV surface antigen (HBsAg), the large HBsAg (LHBs) glycoprotein is expressed preferentially in HBV-associated hepatocellular carcinoma. LHBs can act as an oncogene in transgenic mice, but how it contributes functionally to hepatocarcinogenesis remains unclear. In this study, we determined the molecular and functional roles of LHBs during HBV-associated hepatocarcinogenesis. LHBs increased tumor formation of hepatoma cells. Moreover, expression of LHBs but not other HBV envelope glycoproteins specifically promoted proliferation of hepatoma and hepatic cells in vitro. Mechanistic investigations revealed that these effects were caused by activation of the Src/PI3K/Akt pathway through proximal stimulation of PKCα/Raf1 signaling by LHBs. Proliferation induced by stable LHBs expression was associated with increased G(1)-S cell-cycle progression and apoptosis resistance mediated by Src kinase activation, as established in hepatocellular carcinoma clinical specimens. Importantly, LHBs-induced cellular proliferation and tumor formation were reversed by administration of the Src inhibitor saracatinib. Together, our findings suggest that LHBs promotes tumorigenesis of hepatoma cells by triggering a PKCα/Raf1 to Src/PI3K/Akt signaling pathway, revealing novel insights into the underlying mechanisms of HBV-associated hepatocarcinogenesis.
Onycholemmal carcinoma: A morphologic comparison of 6 reported cases
Authors: Brad E. Chaser, Krystal M. Renszel, A. Neil Crowson, Anita Osmundson, Igor V. Shendrik, Edward H. Yob, G. Scott Drew, Paul R. Callegari, Shannon Campbell, Jan V. Pitha, Cynthia M. Magro
Journal: Journal of the American Academy of Dermatology (2012)
Recurrent aortopulmonary artery fistula
Authors: B. F. Buxton, D. A. Cooley
Journal: Thorax (1973)

<b>Buxton, B. F., and Cooley, D. A. (1973)</b>. <i>Thorax</i>, <b>28</b>, 521-525. <b>Recurrent aortopulmonary artery fistula</b>. The case report is presented of a patient who underwent successful repair of a recurrent fistula between the aorta and the pulmonary artery secondary to an atherosclerotic aneurysm of the ascending thoracic aorta. The fistula was situated between the proximal part of the ascending aorta and the proximal part of the main pulmonary artery and was associated with aortic incompetence together with pulmonary valvular stenosis and incompetence. The repair involved prosthetic replacement of both the pulmonary and aortic valves, the main pulmonary artery, and the ascending thoracic aorta.
Obesity as a Mediator of the Influence of Cardiorespiratory Fitness on Cardiometabolic Risk: A Mediation Analysis
Authors: Ana Díez-Fernández, Mairena Sánchez-López, Ricardo Mora-Rodríguez, Blanca Notario-Pacheco, Coral Torrijos-Niño, Vicente Martínez-Vizcaíno
Journal: Diabetes Care (2013)

The relationship between cardiorespiratory fitness (CRF) and metabolic syndrome (MetS) is well known, although the extent to which body weight may act as a confounder or mediator in this relationship is uncertain. The aim of this study was to examine whether the association between CRF and cardiometabolic risk factors is mediated by BMI.A cross-sectional study including 1,158 schoolchildren aged 8-11 years from the province of Cuenca, Spain, was undertaken. We measured height, weight, waist circumference (WC), blood pressure, fasting plasma lipid profile and insulin, and CRF (20-m shuttle run test). A validated cardiometabolic risk index was estimated by summing standardized z scores of WC, log triglyceride-to-HDL cholesterol ratio (TG/HDL-c), mean arterial pressure (MAP), and log fasting insulin. To assess whether the association between CRF and cardiometabolic risk was mediated by BMI, linear regression models were fitted according to Baron and Kenny procedures for mediation analysis.In girls, BMI acts as a full mediator in the relationship between CRF and cardiometabolic risk factors, with the exception of log TG/HDL-c ratio. In boys, BMI acts as a full mediator in the relationship between CRF and both log TG/HDL-c ratio and MAP, and as a partial mediator in the relationship between CRF and cardiometabolic risk factors.BMI mediates the association between CRF and MetS in schoolchildren. Overall, good levels of CRF are associated with lower cardiometabolic risk, particularly when accompanied by weight reduction.
Familial Hypercholesterolemia (One Form of Familial Type II Hyperlipoproteinemia) A STUDY OF ITS BIOCHEMICAL, GENETIC, AND CLINICAL PRESENTATION IN CHILDHOOD
Authors: Peter O. Kwiterovich, Donald S. Fredrickson, Robert I. Levy
Journal: Journal of Clinical Investigation (1974)

Primary hyperbetalipoproteinemia (type II hyperlipoproteinemia) is a common disorder associated with premature vascular disease. It is frequently due to genetic abnormalities, some of which are expressed in childhood. We have examined the manner in which that form of hyperbetalipoproteinemia known as familial hypercholesterolemia may be expressed in 236 children aged 1-19 born of 90 matings in which one parent had hyperbetalipoproteinemia of this variety and one parent did not.
Long-Term Propensity Score–Matched Comparison of Percutaneous Closure of Patent Foramen Ovale With Medical Treatment After Paradoxical Embolism
Authors: Andreas Wahl, Peter Jüni, Marie-Luise Mono, Bindu Kalesan, Fabien Praz, Laura Geister, Lorenz Räber, Krassen Nedeltchev, Heinrich P. Mattle, Stephan Windecker, Bernhard Meier
Journal: Circulation (2012)

Background— Patients with ischemic stroke or transient ischemic attack presumably related to patent foramen ovale (PFO) are at risk for recurrent cerebrovascular events. Differences in long-term clinical outcome were investigated among patients with percutaneous PFO closure and those who received medical treatment. Methods and Results— Between 1994 and 2000, 308 consecutive patients with cerebrovascular events presumably related to PFO underwent either percutaneous PFO closure (150 patients) or medical treatment (158 patients). Patients were followed up prospectively for up to 15 years. Seven patients were lost during follow-up. The primary outcome was a composite of stroke, transient ischemic attack, or peripheral embolism. We analyzed 103 propensity score–matched pairs of patients who underwent percutaneous PFO closure or medical treatment. At a median follow-up of 9 years, the primary composite outcome occurred in 11 patients slated to PFO closure (11%) and 22 patients slated to medical treatment (21%; hazard ratio=0.43; 95% confidence interval=0.20–0.94; P =0.033). The treatment effect was driven by a decrease in the risk of transient ischemic attack of 5% versus 14%, respectively (hazard ratio=0.31; 95% confidence interval=0.10–0.94; P =0.039). The risk of all-cause (6% in both groups) and cardiovascular (3% in both groups) mortality appeared to be identical. Conclusion— In this long-term observational, propensity score–matched study, percutaneous PFO closure was more effective than medical treatment for the secondary prevention of recurrent cerebrovascular events among patients with PFO-related transient ischemic attack or stroke.
Bone Marrow or Peripheral Blood for Reduced-Intensity Conditioning Unrelated Donor Transplantation
Authors: Mary Eapen, Brent R. Logan, Mary M. Horowitz, Xiaobo Zhong, Miguel-Angel Perales, Stephanie J. Lee, Vanderson Rocha, Robert J. Soiffer, Richard E. Champlin
Journal: Journal of Clinical Oncology (2014)

There have been no randomized trials that have compared peripheral blood (PB) with bone marrow (BM) grafts in the setting of reduced-intensity conditioning (RIC) transplantations for hematologic malignancy. Because immune modulation plays a significant role in sustaining clinical remission after RIC, we hypothesize that higher graft-versus-host disease (GVHD) associated with PB transplantation may offer a survival advantage.The primary outcome evaluated was overall survival. Cox regression models were built to study outcomes after transplantation of PB (n = 887) relative to BM (n = 219) for patients with acute myeloid leukemia, myelodysplastic syndrome, or non-Hodgkin lymphoma, the three most common indications for unrelated RIC transplantation. Transplantations were performed in the United States between 2000 and 2008. Conditioning regimens consisted of an alkylating agent and fludarabine, and GVHD prophylaxis involved a calcineurin inhibitor (CNI) with either methotrexate (MTX) or mycophenolate mofetil (MMF).After adjusting for age, performance score, donor-recipient HLA-match, disease, and disease status at transplantation (factors associated with overall survival), there were no significant differences in 5-year rates of survival after transplantation of PB compared with BM: 34% versus 38% with CNI-MTX and 27% versus 20% with CNI-MMF GVHD prophylaxis.Survival after transplantation of PB and BM are comparable in the setting of nonirradiation RIC regimens for hematologic malignancy. The effect of GVHD prophylaxis on survival merits further evaluation.
Myocardial fiber diameter and regional distribution in the ventricular wall of normal adult hearts, hypertensive hearts and hearts with hypertrophic cardiomyopathy.
Authors: T Hoshino, H Fujiwara, C Kawai, Y Hamashima
Journal: Circulation (1983)

Myocardial fiber diameters were measured to determine their distribution throughout the ventricular wall in normal adult hearts, hypertensive hearts and hearts with hypertrophic cardiomyopathy (HCM). In normal adult hearts and hypertensive hearts, the diameter decreased from the inner to the outer third of the left ventricular free wall and from the left ventricular side to the right ventricular side of the septum. In HCM, these regional differences were preserved in the left ventricular free wall, but not in the septum. The diameter was greatest in the middle third of the septum, where myocardial fiber disarray was widely distributed. The diameters of the fibers in the right ventricular side of the septum were significantly larger than those of the fibers in the left ventricular side of the septum in HCM. This finding, in contrast to that in normal adult hearts or hypertensive hearts, was considered to be related to the inward convex curvature of the left ventricular chamber. Although there was no significant difference in the diameter of myocardial fibers in the left ventricular free wall between hypertensive hearts and hearts with HCM, the diameters of those in the right ventricular free wall, in the right ventricular side of the septum and in the middle third of the septum were significantly larger in HCM than in hypertensive hearts. We conclude that there is a transmural variation of myocardial fiber diameter in the left ventricular free wall and the ventricular septum, and such transmural variation in HCM is clearly different from that in hypertensive hearts.