tbuckley/cabot-search huggingface dataset:
Acute Blood Pressure Responses in Healthy Adults During Controlled Air Pollution Exposures
Authors: Bruce Urch, Frances Silverman, Paul Corey, Jeffrey R. Brook, Karl Z. Lukic, Sanjay Rajagopalan, Robert D. Brook
Journal: Environmental Health Perspectives (2005)

Exposure to air pollution has been shown to cause arterial vasoconstriction and alter autonomic balance. Because these biologic responses may influence systemic hemodynamics, we investigated the effect of air pollution on blood pressure (BP). Responses during 2-hr exposures to concentrated ambient fine particles (particulate matter < 2.5 microm in aerodynamic diameter; PM2.5) plus ozone (CAP+O3) were compared with those of particle-free air (PFA) in 23 normotensive, nonsmoking healthy adults. Mean concentrations of PM2.5 were 147 +/- 27 versus 2 +/- 2 microg/m3, respectively, and those of O3 were 121 +/- 3 versus 8 +/- 5 ppb, respectively (p < 0.0001 for both). A significant increase in diastolic BP (DBP) was observed at 2 hr of CAP+O3 [median change, 6 mm Hg (9.3%); binomial 95% confidence interval (CI), 0 to 11; p = 0.013, Wilcoxon signed rank test] above the 0-hr value. This increase was significantly different (p = 0.017, unadjusted for basal BP) from the small 2-hr change during PFA (median change, 1 mm Hg; 95% CI, -2 to 4; p = 0.24). This prompted further investigation of the CAP+O3 response, which showed a strong association between the 2-hr change in DBP (and mean arterial pressure) and the concentration of the organic carbon fraction of PM2.5 (r = 0.53, p < 0.01; r = 0.56, p < 0.01, respectively) but not with total PM2.5 mass (r < or = 0.25, p > or = 0.27). These findings suggest that exposure to environmentally relevant concentrations of PM2.5 and O3 rapidly increases DBP. The magnitude of BP change is associated with the PM2.5 carbon content. Exposure to vehicular traffic may provide a common link between our observations and previous studies in which traffic exposure was identified as a potential risk factor for cardiovascular disease.
PATHOGENESIS OF INFLAMMATION
Authors: John M. Moses, Robert H. Ebert, Richard C. Graham, Katherine L. Brine
Journal: The Journal of Experimental Medicine (1964)

Material obtained from the in vitro incubation of granulocytes from saline-induced peritoneal exudates of rabbits has been shown to produce inflammation and fever in rabbits. The supernatant material from cells incubated in saline has been termed granulocytic substance (GS) and is heat-labile. Its production is temperature dependent, occurring at 37 degrees C but not at 4 degrees C, requires viable cells, and is inhibited by potassium ions. A similar material is liberated when cells are incubated in a more physiologic medium. Freezing and thawing of granulocytes does not release GS and the active principle cannot be obtained from the incubation of lymphocytes. GS produces a delayed inflammatory response as measured by leucocyte sticking and emigration in the rabbit ear chamber and the leakage of protein-conjugated dye at the site of intradermal injection. The former response can be accurately quantitated by calculation of the inflammatory index from reactions observed in the ear chamber. The inflammatory reaction and the properties of GS distinguish it from a variety of previously described mediators of inflammation, but GS appears to be identical with leucocytic pyrogen. The possible role of GS in delayed and protracted inflammation and its relationship to the pathogenesis of fever are discussed.
Prostaglandin-oxytocin enhancement.
Authors: M Seppala, P Vara
Journal: BMJ (1972)

Dr. Arnold Gillespie (January 15, p.150) indicates that uterine contractions can be enhanced if oxytocin is given after previous exposure to prostaglandin E2 (PGE2). Brummer showed by in vitro experiments that after exposure to the PGE2, but not to the PGF2alpha, human myometrial strips exhibited an enhanced response to oxytocin. We report here preliminary results on the abortifacient effect of a combined treatment with PGF2alpha and oxytocin. The combined treatment, administered extraamniotically by means of a Foley catheter introduced between the fetal membranes and the uterine wall through the cervical canal, was given to 32 women admitted to the hospital for termination of midtrimester pregnancies. A dose of 0.5 mg PGF2alpha (Astra) was given hourly to 20 women. Higher doses (0.75-2.0 mg) were used if the uterine contractions were weak or lacking. 9 women received a mixture containing 0.5 mg of PGF2alpha and 1 I.U. of oxytocin, and 3 women received 3 I.U. of oxytocin alone. In the PGF2 alpha group of 20 patients, abortion was complete in 7 and incomplete in 10 cases. 3 failures were encountered. The trial was considered a failure if uterine contractions stopped in spite of continuous and increased dosage. In the group of 9 women who received a mixture of PGF2alpha and oxytocin, there was no failure. Abortion was complete in 5 and incomplete in 4 cases. Of the 3 women who received oxytocin only, 1 aborted and 2 failed. Uterine contractions were present in all 3 cases. The mean dose of PGF2alpha required for an abortion was 26.1 mg in the PG group, while that in the combined PGF2alpha and oxytocin group was 15.2 mg. 2 of 3 failures in the PG group were successfully treated with an intravenous oxytocin infusion (5 I.U./hour), which caused uterine contractions when PG had no further effect. Hysterotomy was needed in 1 case, where a bicornuate uterus was found at the operation. Extraamniotic oxytocin alone caused uterine contractions in all 3 cases included in the trial, although abortion was achieved in only 1 case. The 2 failures in the oxytocin group were treated with extraamniotic PG. In the total series of 32 cases, hysterotomy was not required in 31 (97%) if both PG and oxytocin were used. PGF2alpha and oxytocin have a contractile effect on the uterus in vivo during midtrimester. Whether the effects of these 2 drugs are additive or potentiative is now being studied.
Clinical Management of Leukoplakia of the Renal Pelvis
Authors: F. Brantley Scott
Journal: JAMA (1960)

Leukoplakia of the renal pelvis can be diagnosed preoperatively. Yet in only six of the reported cases has the diagnosis been made before surgery. This lesion is premalignant, and the treatment in the unilateral case is nephrectomy. All three of the cases here reported were diagnosed before surgery by means of the history, suspicious findings of pyelographic examination, and cell block studies of the urine. The most dramatic symptom may be flank pain associated with the passage of "sheets" from the shedding lesion. Pyelograms typically show linear striations or mottling which should arouse suspicion. The presence of keratin or keratinized squamous cells in the urine cell block study is pathognomonic. The treatment of unilateral leukoplakia of the renal pelvis in these cases was nephrectomy. This was curative, as shown when the three patients were reexamined four to five years later.
HORMONAL MANAGEMENT OF HEREDITARY HEMORRHAGIC TELANGIECTASIA
Authors: Henry J. Koch
Journal: JAMA (1952)

The purpose of this paper is to report a new method for reducing the tendency to hemorrhage in patients with  hemorrhagic telangiectasia (Osler-Rendu disease). Although the periods of observation of the patients treated were of short duration, the longest having been just over one year, the results to date of writing were of sufficient interest to merit a preliminary report.  DEFINITION  The term  hemorrhagic telangiectasia was first advocated by Hanes1in 1909. He defined this disease as a hereditary affection manifesting itself in localized dilatations of the capillaries and venules forming distinct groups of telangiectases which occur upon the skin of the face, nasal and buccal mucous membranes, and give rise to profuse hemorrhage either spontaneously or as a result of trauma. The cardinal findings for the establishment of the diagnosis of this disease are contained in Hanes' definition: (1) the  tendency toward the disease, (2)
ACUTE SUBDELTOID BURSITIS
Authors: Samuel C. Harvey
Journal: JAMA (1941)

To the Editor:—  InThe Journal, March 8, appears an excellent editorial concerning acute subdeltoid bursitis, with particular reference to its treatment. This consists of needling of the bursa, the effectiveness of which has been recently emphasized by Alanson Weeks. Unfortunately no citation was made of the original suggestion of Flint inThe Journalin 1913 (Flint, J. M.: Acute Traumatic Subdeltoid Bursitis, April 19, 1913, p. 1224) of aspiration of the bursa in this condition, reporting its successful use in two cases. This omission is perhaps excusable in that no reference is made to Flint's contribution in the article of Patterson and Darrach, referred to in your editorial, and although Weeks gives credit to Flint for its use in acute subdeltoid bursitis he states that unfortunately he said nothing about this treatment for all forms of the disease. As a matter of fact, Flint stated in his paper It
Paradoxical Splitting of the Second Heart Sound in Coronary Heart Disease
Authors: Peter M. Yurchak, Richard Gorlin
Journal: New England Journal of Medicine (1963)

DISTINCTIVE auscultatory findings in coronary disease are notably few, and any additional bedside clue to the diagnosis is of value. It seems pertinent to report our observations of paradoxical, or reversed, splitting of the second heart sound in 7 patients with proved coronary disease.Case ReportsR.G. (P.B.B.H. 2–22–65), a 70-year-old man, had been treated for an acute myocardial infarction elsewhere 8 years previously. Subsequently, he had episodic pain in the left side of the chest on exertion, relieved by rest or nitroglycerin. He was admitted to the hospital because of a marked increase in the severity of the chest . . .
Monitoring treatment response in precapillary pulmonary hypertension using non-invasive haemodynamic measurements
Authors: Frederik Trinkmann, Dariusch Haghi, Joachim Saur
Journal: Thorax (2011)

Lee et al should be commended for showing that non-invasive haemodynamic monitoring using inert gas rebreathing (IGR) might be a valuable tool to detect treatment response in patients with precapillary pulmonary hypertension (PH).1 Even under resting conditions, haemodynamic parameters may be more sensitive than the 6-minute walk distance. This is especially interesting as it may facilitate frequent therapy monitoring. Although pulmonary blood flow (PBF) …
Pancreatic and synovial type phospholipases A2 in serum samples from patients with severe acute pancreatitis.
Authors: T J Nevalainen, J M Gronroos, P T Kortesuo
Journal: Gut (1993)

Phospholipase A2 (PLA2) is the rate limiting enzyme in the formation of prostaglandins and probably plays a key part in the pathology of various inflammatory diseases. In acute pancreatitis, the catalytic activity of PLA2 in serum correlates with the severity of the disease. The cellular source of the catalytically active PLA2 in serum of patients suffering from acute pancreatitis and other diseases is unknown. Immunoassays for the measurement of pancreatic group I PLA2 and nonpancreatic synovial type group II PLA2 have recently been developed and the present study investigated the presence of group I and group II PLA2s in serum samples from 36 patients with severe acute pancreatitis. The catalytic activity of PLA2 showed a highly significant correlation with the concentration of synovial type PLA2 (r = 0.939, p = 0.001) but not with the concentration of pancreatic PLA2 (r = 0.067, p = 0.698). The results suggest that pancreatic PLA2 circulates mostly as inactive enzyme in patients with acute pancreatitis whereas synovial type PLA2 is responsible for the increased catalytic activity of the enzyme and thus might be associated with the pathophysiology of the disease.
Interferon gamma induces the expression of human immunodeficiency virus in persistently infected promonocytic cells (U1) and redirects the production of virions to intracytoplasmic vacuoles in phorbol myristate acetate-differentiated U1 cells.
Authors: P Biswas, G Poli, A L Kinter, J S Justement, S K Stanley, W J Maury, P Bressler, J M Orenstein, A S Fauci
Journal: The Journal of Experimental Medicine (1992)

Interferon gamma (IFN-gamma), a lymphokine that exerts multiple immunoregulatory effects, has been found to be elevated in the plasma, cerebrospinal fluid, and lymph nodes of human immunodeficiency virus (HIV)-infected individuals and has shown variable effects on HIV replication in acutely infected cells. In the present study, we have demonstrated that IFN-gamma is a potent modulator of HIV expression in persistently infected U1 promonocytic cells in which virus production is characterized by a constitutive state of relative latency. Direct stimulation of U1 cells with IFN-gamma (10-1,000 U/ml) activated HIV expression, as measured by reverse transcriptase (RT) activity in the culture supernatant and increased levels of cell-associated viral protein and mRNAs. These effects on virus expression were not accounted for by the induction of endogenous TNF-alpha secretion, as previously described in U1 cells stimulated with phorbol myristate acetate (PMA). At the ultrastructural level, the stimulatory activity of IFN-gamma was correlated with HIV particle production in intracytoplasmic vacuoles along with the differentiation of U1 into macrophage-like cells. Furthermore, costimulation of U1 cells with IFN-gamma and PMA significantly increased the accumulation of vacuole-associated HIV concomitant with decreasing membrane-associated particles and RT activity production, as compared with cells stimulated with PMA alone. No evidence of spontaneous secretion of intracellular vacuole-associated virus was obtained by kinetic analysis of the RT activity released in the supernatants throughout the culture period unless cells were deliberately disrupted. These findings suggest that vacuole-associated virions likely represent a relatively stable intracellular reservoir of HIV, as previously described in primary macrophages infected in vitro or in infected macrophages in the brains of patients with acquired immune deficiency syndrome. The reduced levels of RT activity observed in the culture supernatants of U1 cells stimulated with PMA in the presence of IFN-gamma were not indicative of a suppressive effect of IFN-gamma on PMA-induced expression of HIV proteins and mRNAs, either directly or mediated by the release of IFN-alpha/beta. This study suggests that IFN-gamma may play an important role as an inducer of HIV expression in infected mononuclear phagocytes.
SF3B1 mutations are prevalent in myelodysplastic syndromes with ring sideroblasts but do not hold independent prognostic value
Authors: Mrinal M. Patnaik, Terra L. Lasho, Janice M. Hodnefield, Ryan A. Knudson, Rhett P. Ketterling, Guillermo Garcia-Manero, David P. Steensma, Animesh Pardanani, Curtis A. Hanson, Ayalew Tefferi
Journal: Blood (2011)
p53 prevents maturation to the CD4+CD8+ stage of thymocyte differentiation in the absence of T cell receptor rearrangement.
Authors: D Jiang, M J Lenardo, J C Zúñiga-Pflücker
Journal: The Journal of Experimental Medicine (1996)

Rearrangement of the immunoglobulin (Ig) and T cell receptor (TCR) gene loci allows for the generation of B and T lymphocytes with antigen-specific receptors. Complete rearrangement and expression of the TCR-beta chain enables immature thymocytes to differentiate from the CD4-CD8- to the CD4+CD8+ stage mice in which rearrangement is impaired, such as severe combined immunodeficient (SCID) mice or recombinase activating gene-deficient (RAG-/-) mice, lack mature B and T lymphocytes. Thymocytes from these mice are arrested at the CD4-CD8- stage of T cell development. We previously observed that thymocytes from RAG-2-/- mice exposed to gamma radiation differentiate from CD4-CD8- into CD4+CD8+ without TCR-beta chain rearrangement. We now report that irradiated RAG-2-/- thymocytes undergo direct somatic mutations at the p53 gene locus, and that p53 inactivation is associated with maturation of RAG2-/- thymocytes to the CD4+CD8+ stage. Generation of RAG2-/- and p53-/- double-deficient mice revealed that, in the absence of TCR-beta chain rearrangement, loss of p53 function is sufficient for CD4-CD8- thymocytes to differentiate into the CD4+CD8+ stage of T cell development. Our data provide evidence for a novel p53 mediated checkpoint in early thymocyte development that regulates the transition of CD4-CD8- into CD4+CD8+ thymocytes.
Inhibition of Angiogenesis and Murine Hemangioma Growth by Batimastat, a Synthetic Inhibitor of Matrix Metalloproteinases
Authors: G. Taraboletti, A. Garofalo, D. Belotti, T. Drudis, P. Borsotti, E. Scanziani, P. D. Brown, R. Giavazzi
Journal: JNCI Journal of the National Cancer Institute (1995)

Background : The importance of matrix metalloproteinases in angiogenesis, tumor growth, and metastasis is well known. However, little is known about the role of matrix metalloproteinases in the formation of hemangiomas and about the possible therapeutic use of matrix metalloproteinase inhibitors in aggressive vascular tumors. Purpose : To study the role of matrix metalloproteinase in vascular tumors, we tested the antineoplastic activity of a synthetic inhibitor of matrix metalloproteinases, batimastat, on an experimental model of hemangioma, formed by murine endothelioma cells transformed by polyoma middle-T on-cogene (eEnd.l). Methods : The effect of batimastat was studied in vivo on the formation of hemorrhaging, cavernous hemangiomas by eEnd.l endothelioma cells injected subcutaneously in nude mice and on the angiogenic response induced by an endothelioma cell supernatant embedded in a pellet of reconstituted basement membrane (Matrigel). The effect of batimastat was investigated in vitro on endothelial cell proliferation, motility, and invasion of a layer of Matrigel. Results : Daily treatment with batimastat (30, 3, and 0.3 mg/kg at the site of eEnd.l cell injection) inhibited tumor growth, with increased doubling time. The car-boxamide derivative of batimastat, BB-374, a poor inhibitor of matrix met-alloproteinase activity, was less active in reducing hemangioma growth. His-tologic analysis of treated tumors indicated a reduction in the size of blood-filled spaces and in hemorrhage. Batimastat also inhibited the angio-genic response induced by cultured eEnd.l endothelioma cell supernatant embedded in a pellet of Matrigel. Batimastat significantly inhibited endo-thelial cell invasion in vitro through a layer of Matrigel, but it showed no direct cytotoxic activity. Conclusions : Batimastat reduces in vivo growth of experimental hemangiomas, most probably by blocking endothelial cell recruitment by the transformed cells or by interfering with cell organization in vascular structures. Implications : These results confirm the importance of matrix metalloproteinase in endothelial cell recruitment that occurs in angiogenesis and in the formation of vascular tumors and suggest a therapeutic potential for synthetic matrix metalloproteinase inhibitors. [J Natl Cancer Inst 87: 293-298, 1995]
Effect of Fructose on Body Weight in Controlled Feeding Trials
Authors: John L. Sievenpiper, Russell J. de Souza, Arash Mirrahimi, Matthew E. Yu, Amanda J. Carleton, Joseph Beyene, Laura Chiavaroli, Marco Di Buono, Alexandra L. Jenkins, Lawrence A. Leiter, Thomas M.S. Wolever, Cyril W.C. Kendall, David J.A. Jenkins
Journal: Annals of Internal Medicine (2012)

Background: The contribution of fructose consumption in Western diets to overweight and obesity in populations remains uncertain. Purpose: To review the effects of fructose on body weight in controlled feeding trials. Data Sources: MEDLINE, EMBASE, CINAHL, and the Cochrane Library (through 18 November 2011). Study Selection: At least 3 reviewers identified controlled feeding trials lasting 7 or more days that compared the effect on body weight of free fructose and nonfructose carbohydrate in diets providing similar calories (isocaloric trials) or of diets supplemented with free fructose to provide excess energy and usual or control diets (hypercaloric trials). Trials evaluating high-fructose corn syrup (42% to 55% free fructose) were excluded. Data Extraction: The reviewers independently reviewed and extracted relevant data; disagreements were reconciled by consensus. The Heyland Methodological Quality Score was used to assess study quality. Data Synthesis: Thirty-one isocaloric trials (637 participants) and 10 hypercaloric trials (119 participants) were included; studies tended to be small (<15 participants), short (<12 weeks), and of low quality. Fructose had no overall effect on body weight in isocaloric trials (mean difference, −0.14 kg [95% CI, −0.37 to 0.10 kg] for fructose compared with nonfructose carbohydrate). High doses of fructose in hypercaloric trials (+104 to 250 g/d, +18% to 97% of total daily energy intake) lead to significant increases in weight (mean difference, 0.53 kg [CI, 0.26 to 0.79 kg] with fructose). Limitations: Most trials had methodological limitations and were of poor quality. The weight-increasing effect of fructose in hypercaloric trials may have been attributable to excess energy rather than fructose itself. Conclusion: Fructose does not seem to cause weight gain when it is substituted for other carbohydrates in diets providing similar calories. Free fructose at high doses that provided excess calories modestly increased body weight, an effect that may be due to the extra calories rather than the fructose. Primary Funding Source: Canadian Institutes of Health Research. (ClinicalTrials.gov registration number: NCT01363791)