tbuckley/cabot-search huggingface dataset:
Appearance and Characterization of Lipoprotein X during Continuous Intralipid Infusions in the Neonate
Authors: E. Griffin, W. C. Breckenridge, A. Kuksis, M. H. Bryan, A. Angel
Journal: Journal of Clinical Investigation (1979)

The development of hyperphospholipidemia and hypercholesterolemia was studied in infants that required total parenteral nutrition and given a continuous infusion of Intralipid, (1-4 g/kg body wt per 24 h. Detailed studies were carried out on infusion periods lasting 1-10 d. After 24 h there was a marked increase in plasma free cholesterol (68%) and phospholipid (77%) concentrations. Based on the amount of cholesterol in Intralipid, and the rate of infusion, it was estimated that at least 50% of the plasma cholesterol increment during 64-h infusions was derived from endogenous sources. By contrast, the hyperphospholipidemia could be attributed to the Intralipid as the rise in plasma was calculated to be equivalent to only 16% of the exogenous phospholipid infused. Approximately 10% of the phospholipid in Intralipid was in a triglyceride-free mesophase form with a free cholesterol:phospholipid molar ratio of 0.063. There were no systematic changes in plasma concentrations of cholesterol ester or triglyceride during Intralipid infusions. The increase in free cholesterol and phospholipid was localized in the low density lipoproteins (d = 1.006-1.063 g/ml). The presence of lipoprotein X (Lp-X) in the low density lipoprotein fraction was demonstrated by electrophoresis in agar and by isolation and chemical characterization with hydroxylapatite chromatography. Isoelectric focusing of urea-soluble protein of Lp-X revealed that albumin and apolipoproteins CII and CIII were major components, whereas apolipoprotein E and AI were minor constituents. The abnormal lipoprotein was apparent by 16 h during 64 h of infusion. After 6 d of continuous infusions the free cholesterol in Lp-X was 30±10 mg/dl (mean±SD), which represents a total Lp-X mass of 90 mg/dl. After cessation of the infusion, Lp-X, as monitored by electrophoresis in agar, disappeared within 72-96 h. Thus, during infusion of Intralipid in infants at rates commonly employed, the capacity of the clearance mechanisms for phospholipid are exceeded, which causes the accumulation of phospholipid and free cholesterol in the form of Lp-X particles. It is suggested that mesophase phospholipids in Intralipid may play a significant role in this process.
Exposure to trichloramine and respiratory symptoms in indoor swimming pool workers
Authors: J. H. Jacobs, S. Spaan, G. B. G. J. van Rooy, C. Meliefste, V. A. C. Zaat, J. M. Rooyackers, D. Heederik
Journal: European Respiratory Journal (2006)

The association between swimming pool characteristics and activities of employees and respiratory symptoms in employees was studied. Trichloramine levels were measured to evaluate relationships with pool characteristics and to estimate long-term exposure levels. Questionnaires were available from 624 pool workers and 38 swimming facilities. Chloramine levels were measured by area sampling over 2-h periods and analysed using ion chromatography. Work-related and general respiratory symptoms, and symptoms indicative of atopy and bronchial hyperresponsiveness were considered. Respiratory symptom prevalence among pool workers was compared with symptoms in a Dutch population sample. Chloramine levels were modelled with regression analysis. This model was used to estimate long-term average chloramine levels for each pool studied. Employees with higher exposure reported upper respiratory symptoms with greater frequency. Upper respiratory symptoms were statistically significantly associated with cumulative chloramine levels (odds ratio (OR) >1.4 for hoarseness, lost voice, sinusitis). General respiratory symptoms were significantly elevated compared with a Dutch population sample (OR ranged 1.4-7.2). An excess risk for respiratory symptoms indicative of asthma was observed in swimming pool employees. Aggravation of existing respiratory disease or interactions between irritants and allergen exposures are the most likely explanations for the observed associations.
THE CANADIAN AMERICAN TICLOPIDINE STUDY (CATS) IN THROMBOEMBOLIC STROKE
Authors: Michael Gent, J. Donald Easton, VladimirC. Hachinski, Edouard Panak, Jane Sicurella, JohnA. Blakely, DavidJ. Ellis, JohnW. Harbison, RobinS. Roberts, AlexanderG.G. Turpie
Journal: The Lancet (1989)
Bone marrow derivation of pericryptal myofibroblasts in the mouse and human small intestine and colon
Authors: M Brittan
Journal: Gut (2002)

In order to establish whether extraintestinal cells contribute to the turnover and repair of gastrointestinal tissues, we studied the colons and small intestines of female mice that had received a male bone marrow transplant, together with gastrointestinal biopsies from female patients that had developed graft versus host disease after receiving a bone marrow transplant from male donors.Using in situ hybridisation to detect Y chromosomes and immunohistochemistry, we demonstrated that cells derived from injected bone marrow frequently engrafted into the intestine and differentiated into pericryptal myofibroblasts.In the human intestine, we confirmed by combining in situ hybridisation with immunostaining for smooth muscle actin that the bone marrow derived cells within the intestine exhibited a myofibroblast phenotype. In female mouse recipients of male bone marrow grafts, we observed colocalisation of Y chromosomes and clusters of newly formed marrow derived myofibroblasts. While few of these were present at seven days after bone marrow transplantation, they were numerous at 14 days, and by six weeks entire columns of pericryptal myofibroblasts could be seen running up the sides of crypts in both the small intestine and colon. These columns appeared to extend into the villi in the small intestine. Within the intestinal lamina propria, these Y chromosome positive cells were negative for the mouse macrophage marker F4/80 antigen and CD34.Bone marrow derived pericryptal myofibroblasts were present in the mouse intestine following irradiation and bone marrow transplant, and in the intestines of human patients suffering graft versus host disease following a bone marrow transplant. Our data indicate that bone marrow cells contribute to the regeneration of intestinal myofibroblasts and epithelium after damage, and we suggest that this could be exploited therapeutically.
Metabolic Gene Expression in Fetal and Failing Human Heart
Authors: Peter Razeghi, Martin E. Young, Joseph L. Alcorn, Christine S. Moravec, O.H. Frazier, Heinrich Taegtmeyer
Journal: Circulation (2001)

Background — Previous studies suggest that the failing heart reactivates fetal genes and reverts to a fetal pattern of energy substrate metabolism. We tested this hypothesis by examining metabolic gene expression profiles in the fetal, nonfailing, and failing human heart. Methods and Results — Human left ventricular tissue (apex) was obtained from 9 fetal, 10 nonfailing, and 10 failing adult hearts. Using quantitative reverse transcription-polymerase chain reaction, we measured transcript levels of atrial natriuretic factor, myosin heavy chain-α and -β, and 13 key regulators of energy substrate metabolism, of which 3 are considered “adult” isoforms (GLUT4, mGS, mCPT-I) and 3 are considered “fetal” isoforms (GLUT1, lGS, and lCPT-I), primarily through previous studies in rodent models. Compared with the nonfailing adult heart, steady-state mRNA levels of atrial natriuretic factor were increased in both the fetal and the failing heart. The 2 myosin heavy chain isoforms showed the highest expression level in the nonfailing heart. Transcript levels of most of the metabolic genes were higher in the nonfailing heart than the fetal heart. Adult isogenes predominated in all groups and always showed a greater induction than the fetal isogenes in the nonfailing heart compared with the fetal heart. In the failing heart, the expression of metabolic genes decreased to the same levels as in the fetal heart. Conclusions — In the human heart, metabolic genes exist as constitutive and inducible forms. The failing adult heart reverts to a fetal metabolic gene profile by downregulating adult gene transcripts rather than by upregulating fetal genes.
Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype
Authors: Giovanni Cazzaniga, Maria Grazia Dell'Oro, Cristina Mecucci, Emanuela Giarin, Riccardo Masetti, Vincenzo Rossi, Franco Locatelli, Massimo F. Martelli, Giuseppe Basso, Andrea Pession, Andrea Biondi, Brunangelo Falini
Journal: Blood (2005)
Relation Between Serum Phosphate Level and Cardiovascular Event Rate in People With Coronary Disease
Authors: Marcello Tonelli, Frank Sacks, Marc Pfeffer, Zhiwei Gao, Gary Curhan
Journal: Circulation (2005)

Higher levels of serum phosphate are associated with adverse cardiovascular outcomes, especially in the setting of overt hyperphosphatemia. Given the biological importance of phosphorus, it is plausible that higher levels of serum phosphate within the normal range may also be associated with adverse outcomes.We performed a post hoc analysis of data from the Cholesterol And Recurrent Events (CARE) study. Baseline serum phosphate levels were measured in 4127 fasting participants who were randomized to receive pravastatin 40 mg daily or placebo and followed up for a median of 59.7 months. We used Cox proportional-hazards models to examine the association between serum phosphate and adverse clinical outcomes after adjustment for potential confounders. During nearly 60 months of follow-up, 375 participants died. A significant association was noted between baseline serum phosphate level and the age-, race-, and sex-adjusted risk of all-cause death (hazard ratio per 1 mg/dL, 1.27; 95% confidence interval, 1.02 to 1.58). After categorization based on baseline phosphate level (<2.5, 2.5 to 3.4, 3.5 to 3.9, and > or =4 mg/dL) and further adjustment, a graded independent relation between phosphate and death was observed (P for trend=0.03). For instance, participants with serum phosphate > or =3.5 mg/dL had an adjusted hazard ratio for death of 1.27 (95% confidence interval, 1.02 to 1.59) compared with those with serum phosphate of <3.5 mg/dL. Higher levels of serum phosphate were also associated with increased risk of new heart failure, myocardial infarction, and the composite of coronary death or nonfatal myocardial infarction, but not the risk of stroke.We found a graded independent relation between higher levels of serum phosphate and the risk of death and cardiovascular events in people with prior myocardial infarction, most of whom had serum phosphate levels within the normal range. Given the ready availability and low cost of serum phosphate assays, this finding may prove clinically useful.
Philadelphia‐chromosome‐negative chronic myelogenous leukemia with lymphoid stem cell blastic transformation
Authors: P. Bettelheim, W. Knapp, Thomas M. Grogan, John F. Kessler, Bernard R. Greenberg
Journal: American Journal of Hematology (1986)

A patient is described who had blastic transformation of Ph1 negative chronic myelogenous leukemia (Ph1 - CML). Characterization of the leukemic cells revealed a population with a lymphoid stem cell phenotype (cALL-, TdT+, Ia+, cIgM-). This particular phenotype may be responsible for the refractoriness to vincristine and prednisone and the rapid downhill course.
Nonthrombotic pulmonary embolism
Authors: P. G. Jorens, E. Van Marck, A. Snoeckx, P. M. Parizel
Journal: European Respiratory Journal (2009)

Nonthrombotic pulmonary embolism (NTPE) is defined as embolisation to the pulmonary circulation of different cell types (adipocytes, haematopoietic, amniotic, trophoblastic or tumour), bacteria, fungi, foreign material or gas. The purpose of this article is to describe the clinical signs, pathogenesis, diagnosis and treatment of the different NTPE subtypes. The complex and diverse pathogenesis of different subtypes of emboli is subject to continuing speculation and is certainly far more complex than “simple” mechanical obstruction after embolisation of vascular thrombi. Nonthrombotic emboli may also lead to a severe inflammatory reaction both in the systemic and pulmonary circulation, as well as in the lung. NTPE presents a formidable diagnostic challenge, as the condition often presents with very unusual and peculiar clinical signs that are frequently overlooked. They range from very dramatic acute presentations such as acute respiratory distress syndrome to signs observed late in the disease course. Pathological observations play a key role in the exact diagnosis, and sometimes carefully aspirated blood from the pulmonary artery or specific staining of cells recovered from bronchoalveolar lavage fluid may be helpful. Frequently, lung biopsies revealing severe granulomatous reaction or unfortunate post-mortem pathological investigations of pulmonary tissue are necessary to confirm the diagnosis. Here, we also aim to familiarise the reader with the atypical radiological features of NTPE. Thin-section computed tomography of the lungs showing peculiar radiographic findings, such as a feeding vessel, the so-called tree-in-bud pattern or the appearance of micronodules distributed at the termination of bronchovascular bundles, may be observed in certain forms of NTPE. Increased awareness of NTPE as an underestimated cause of acute and chronic embolism, which may result in acute and chronic pulmonary hypertension, is needed. Despite the fact that detailed descriptions of several forms of NTPE have existed for nearly 100 years, well-designed trials have never been performed to evaluate therapy in the different subsets of these patients.
Primary Osteogenic Sarcoma of the Breast Detected on Skeletal Scintigraphy
Authors: Annare Ellmann, Z M. Jawa, Masha Maharaj
Journal: Clinical Nuclear Medicine (2006)

A 74-year-old woman presented with a painless breast mass. Mammography of both breasts showed a large, lobulated calcific dense mass in the upper quadrant of the left breast. A skeletal scan showed very intense concentration of activity in the primary breast tumor in the left breast. A left mastectomy and axillary dissection were performed. The predominant histologic type of the mass was of an osteosarcoma and the diagnosis of a primary osteogenic sarcoma of the breast was made. Primary osteogenic sarcoma of the breast is rare and represents less than 1% of all primary breast malignancies.
Dose ranging study of intravenous RPR 109891 in patients with acute coronary syndromes — results of TIMI 15A
Authors: R.P. Giugliano, C.H. McCabe, R.F. Sequeira, T.D. Henry, R.N. Piana, M.J. Schweiger, H.S. Mueller, S. Borzak, M.D. Tischler, J.-F. Tamby, K.E. Ramsey, M.V. Jacoskj, R.J. Wise, E. Braunwald
Journal: Journal of the American College of Cardiology (1998)
Predictive value of arterial ammonia for complications and outcome in acute liver failure
Authors: V Bhatia
Journal: Gut (2005)

In acute liver failure (ALF), the brain is exposed to high levels of ammonia. Human studies defining the clinical significance of ammonia in ALF are lacking. This prospective study evaluated the relationship of arterial ammonia levels at admission to complications and survival among patients with ALF.Eighty consecutive ALF patients admitted from March 2001 to December 2003 were followed up until death or complete recovery. All had arterial ammonia estimation at admission (enzymatic method). Logistic regression analysis was performed to identify independent predictors of mortality.Forty two (52.5%) patients died. Non-survivors had significantly higher median ammonia levels than survivors (174.7 v 105.0 micromol/l; p<0.001). An arterial ammonia level of > or = 124 micromol/l was found to predict mortality with 78.6% sensitivity and 76.3% specificity, and had 77.5% diagnostic accuracy. Patients with higher ammonia levels also developed more complications, including deeper encephalopathy (p = 0.055), cerebral oedema (p = 0.020), need for ventilation (p<0.001), and seizures (p = 0.006). Logistic regression analysis showed that pH, presence of cerebral oedema, and arterial ammonia at admission were independent predictors of mortality (odds ratios 6.6, 12.6, and 10.9, respectively). Incorporating these variables, a score predicting mortality risk at admission was derived: 2.53 + 2.91 ammonia + 2.41 oedema + 1.40 pH, where ammonia is scored as 0 (if <124 micromol/l) or 1 (if > or =124 micromol/l); oedema is scored as 0 (absent) or 1(present); and pH is scored as 1 (if < or =7.40) or 0 (if >7.40). Levels of partial pressure of ammonia were equally correlated with outcome.Arterial ammonia at presentation is predictive of outcome and can be used for risk stratification. Ammonia lowering therapies in patients with ALF should be evaluated.
Ultrasonographic assessment of fractures: a break in tradition?
Authors: Ian Cheyne, Elizabeth Roy, Bruce B Forster
Journal: British Journal of Sports Medicine (2014)

Portable ultrasound (US) devices continue to improve in technical capabilities while cost decreases allow widespread use beyond traditional sports medicine settings.1 Using US at the field of play is an exciting advance in acute injury assessment. Images submitted as part of Hoffman et al 2 review reflect state-of-the-art quality and great promise. By assessing for bone injury, athletes can be triaged on the field, possibly preventing further trauma by early return. However, ultrasonography examinations in general are highly user dependent, and lack of expertise in scanning can lead to significant error rates.

Ultrasonographic assessment of fractures has high utility and recent literature supports its use when conventional radiographs are unavailable. Specifically, multiple studies in the paediatric population have shown high sensitivity and specificity for US identification of long-bone fractures, while US assessment of paediatric rib fractures have demonstrated accuracy exceeding X-ray.3 However, much of literature on ultrasonographic assessment …
Comparison of Tuberculin Skin Test and New Specific Blood Test in Tuberculosis Contacts
Authors: Inger Brock, Karin Weldingh, Troels Lillebaek, Frank Follmann, Peter Andersen
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The tuberculin skin test used to detect latent Mycobacterium tuberculosis infection has many drawbacks, and a new diagnostic test for latent tuberculosis (QuantiFERON-TB [QTF-TB]) has recently been introduced. This test measures the production of IFN-gamma in whole blood upon stimulation with purified protein derivative (PPD). The QTF-TB test addresses the operational problems with the tuberculin skin test, but, as the test is based on PPD, it still has a low specificity in populations vaccinated with the Bacille Calmette-Guérin (BCG) vaccine. We have modified the test to include the antigens ESAT-6 and CFP-10, which are not present in BCG vaccine strains or the vast majority of nontuberculous mycobacteria. This test was used to detect infection in contacts in a tuberculosis outbreak at a Danish high school. The majority of the contacts were BCG-unvaccinated, which allowed a direct comparison of the skin test and the novel blood test in individuals whose skin test was not confounded by vaccination. An excellent agreement between the two tests was found (94%, kappa value 0.866), and in contrast to the blood test based on PPD, the novel blood test was not influenced by the vaccination status of the subjects tested.
Inosine monophosphate dehydrogenase (IMPDH) as a target in drug discovery
Authors: Qingning Shu, Vasu Nair
Journal: Medicinal Research Reviews (2007)

Abstract Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme of de novo purine nucleotide biosynthesis and is viewed as an important target in the quest for discovery of drugs in the antiviral, antibacterial and anticancer therapeutic areas. This review focuses on the medicinal chemistry, drug discovery and chemical biology of IMPDH. Examples of IMP and cofactor site‐directed inhibitors, allosteric inhibitors and isoform‐selective inhibitors are presented. Comparison of IMPDHs from different organisms is also made to facilitate the design of species‐selective IMPDH inhibitors for drug discovery. Special emphasis in the review is placed on IMPDH from Mycobacterium tuberculosis . © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 2, 219–232, 2008
Deep sequencing on genome-wide scale reveals the unique composition and expression patterns of microRNAs in developing pollen of Oryza sativa
Authors: Li Qin Wei, Long Feng Yan, Tai Wang
Journal: Genome biology (2011)

Pollen development in flowering plants requires strict control of the gene expression program and genetic information stability by mechanisms possibly including the miRNA pathway. However, our understanding of the miRNA pathway in pollen development remains limited, and the dynamic profile of miRNAs in developing pollen is unknown. Using next-generation sequencing technology, we pyrosequenced small RNA populations from rice uninucleate microspores to tricellular pollen and control sporophytic tissues at the genome-wide level. We identified 292 known miRNAs, including members of all 20 families conserved in plants, and 75 novel miRNAs. Of the 292 known miRNAs, 202 were expressed, with 103 enriched, in developing pollen. More than half of these novel miRNAs displayed pollen-or stage-specific expression. Furthermore, analyzing the 367 miRNAs and their predicted targets indicated that correlation in expression profiles of pollen-enriched known miRNAs and their targets significantly differs from that of sporophyte-enriched known miRNAs and their targets in some functional terms, while novel miRNAs appeared to negatively regulate their targets. Importantly, gene ontology abundance analysis demonstrated chromatin assembly and disassembly was important in the targets of bicellular pollen-expressed novel miRNAs. Principal component analysis revealed pollen of all three stages was discriminated from sporophytes, largely because of the novel and non-conserved known miRNAs. Our study, for the first time, revealed the differences in composition and expression profiles of miRNAs between developing pollen and sporophytes, with novel and non-conserved known miRNAs the main contributors. Our results suggest the important roles of the miRNA pathway in pollen development.