tbuckley/cabot-search huggingface dataset:
Magnetic Resonance Imaging (MRI) Technique Detects Differences in Lung Function in Boys and Girls who are at Risk for Asthma
Authors: E.L. Anderson, M.D. Evans, L.P. Salazar, C.J. Tisler, K.A. Roberg, R. Gangnon, D.J. Jackson, J.E. Gern, R. Lemanske Jr., S.B. Fain
Journal: Journal of Allergy and Clinical Immunology (2011)
Abstract 296: Protein kinase D regulates Rho GTPase activity through rhotekin
Authors: Ganesh Varma Pusapati, An Rykx, Sandy Vandoninck, Johan van Lint, Guido Adler, Thomas Seufferlein
Journal: Cancer Research (2010)

Abstract The Protein Kinase D (PKD) family of serine / threonine kinases comprises PKD1,PKD2, and PKD3 and is grouped under the calcium / calmodulin - dependent protein kinase (CAMK) superfamily. PKDs play an important role in various biological processes including proliferation, adhesion, migration, cell shape, survival and apoptosis. Identification of the putative target substrates for this kinase family would provide a deeper insight into their role in the physiological and pathological processes. In the present study, we identified rhotekin (RTKN), an effector protein of small GTPase Rho, as a potential substrate of PKDs. Using the consensus PKD substrate sequence motif scan approach, we identified Ser435 in the C-terminal region of rhotekin as the potential phosphorylatable residue. We generated a phospho-specific antibody corresponding to Ser435 and could validate that Ser435 is indeed the critical amino acid targeted by PKD2 in vivo in HEK-293T cells. The phospho-mimecking mutant of rhotekin (Ser435Glu) when transfected into HEK-293T cells resulted in the increase of endogenous active RhoA GTPase levels, as determined from the Rho activation assay. Rho GTPases were shown to be an important upstream molecules regulating PKD activity in the process of cancer cell migration. However, our results demonstrate for the first time the role of PKDs in the regulation of RhoGTP activity levels. Considering the role of RhoGTPases in various cellular processes, our results provide a hint to the potential regulation of various cellular processes by PKDs through phosphorylation of rhotekin and thereby regulating the activity of RhoGTPases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 296.
Lymph Node T Cell Homeostasis Relies on Steady State Homing of Dendritic Cells
Authors: Meike Wendland, Stefanie Willenzon, Jessica Kocks, Ana Clara Davalos-Misslitz, Swantje I. Hammerschmidt, Kathrin Schumann, Elisabeth Kremmer, Michael Sixt, Angelika Hoffmeyer, Oliver Pabst, Reinhold Förster
Journal: Immunity (2011)
Renal Medullary Heat Clearance in the Dog
Authors: KNUT AUKLAND
Journal: Circulation Research (1967)

Renal medullary heat clearance was investigated in anesthetized dogs to evaluate countercurrent exchange of heat. Sudden changes in the temperature of renal arterial blood were induced by infusion of 3 to 7 ml/min of saline at room temperature. The resulting changes in medullary temperature, measured with fine thermocouples, started with increasing delay from cortex towards the papilla. Average rate constant for heat uptake in the inner medulla was 0.61 min -1 . In the outer medulla, rate constants from 0.6 to 5.0 min -1 were observed, with the higher values in the subcortical zone. Inner medullary clearance rose during diuresis, but was practically uninfluenced by lowering perfusion pressure to 35 mm Hg. Calculated heat conduction (diffusion) from cortex into medulla was close to observed clearances, which are thus mainly determined by heat conduction. Clearance due to flow in vasa recta and loops of Henle was small, presumably due to efficient countercurrent heat exchange, whereas urine flow in collecting ducts is not subject to this effect. Formulas for countercurrent exchange not taking into account length diffusion (parallel to the vasa recta) are not valid for medullary heat exchange. The present heat clearance technique cannot be used for estimating medullary blood flow.
The death of Oscar Wilde
Authors: M. Critchley
Journal: BMJ (1988)

more commonly research becomes incorporated within higher training, so that such experience can be gained with little or no prolongation of senior registrar or equivalent tenure, the more control has to be held over the number of available posts.Geographical spread of senior registrar training and research is another related issue, and I should hate to think that I had made any suggestion which might lead to a perpetuation of the present dis- parity.
226 LONG-TERM ANTIBIOTIC AND PROTON-PUMP INHIBITOR USE ARE STRONG PREDICTORS OF RECURRENT INFECTIONS IN CIRRHOSIS: A PROSPECTIVE MULTI-CENTER STUDY FROM NACSELD
Authors: J.G. O'Leary, K.R. Reddy, F. Wong, P.S. Kamath, H.M. Patton, S.W. Biggins, M.B. Fallon, G. Garcia-Tsao, R.M. Subramanian, G. Brown, R. Malik, L.R. Thacker, J.S. Bajaj
Journal: Journal of Hepatology (2013)
Evidence for a Renal Vascular Mechanism in Renin Release: New Observations with Graded Stimulation by Aortic Constriction
Authors: E. H. BLAINE, J. O. DAVIS
Journal: Circulation Research (1971)

To examine the possibility of a renal intravascular receptor for renin secretion, bilateral ureteral ligation and a two-hour period of renal ischemia were used to produce a nonfiltering kidney model in dogs. In conscious animals with both innervated and denervated, nonfiltering kidneys, hemorrhage and suprarenal aortic constriction produced significant increases in plasma renin activity. To measure renin secretion directly, a unilateral, nonfiltering kidney was produced, and renal blood flow was determined with a square-wave electromagnetic flowmeter in anesthetized dogs. Renin secretion was significantly elevated after a 20 ml/kg hemorrhage in these animals. In another group of dogs, adrenalectomy was combined with renal denervation in the unilateral, nonfiltering kidney model. In these animals hemorrhage produced significant increases in renin secretion. After a recovery period three of these dogs were subjected to graded constriction of the suprarenal aorta. Slight decreases in blood pressure with and without decreases in renal blood flow produced increases in renin secretion. Since increased renin secretion occurred in the absence of sodium delivery to the macula densa, from denervated kidneys, and without the major portion of circulating catecholamines, it is suggested that an intrinsic receptor for renin release is present within the renal vascular tree.
Immune function assays as indicators of chromate exposure.
Authors: C A Snyder, C D Valle
Journal: Environmental Health Perspectives (1991)

The potential immunomodulatory effects of chromium were investigated using a series of in vitro and in vivo studies. Chromium (as K2CrO4) in concentrations spanning five orders of magnitude was added in vitro to T-lymphocyte (concanavalin A) and B-lymphocyte (liposaccharide) mitogen cultures and was found to inhibit T-lymphocyte responses at all concentrations tested and to inhibit B-lymphocyte responses at all but the lowest concentration tested (0.01 mg/L). When the same concentrations of chromium were employed in mixed lymphocyte cultures, antigen-induced thymidine uptake was inhibited at the highest concentrations (100 mg/L-1 mg/L), enhanced at 0.1 mg/L, and equal to control values at lower concentrations. Splenocytes isolated from rats exposed to K2CrO4 in drinking water exhibited enhanced responses to T- and B-lymphocyte mitogens. The addition of 0.1 mg/L of chromium to a mixed lymphocyte culture containing splenocytes taken from chromium-exposed rats increased by 5-fold the uptake of thymidine by these cells. These increased responses of cells from chromium-exposed rats may indicate chromium-induced sensitization and may possibly be used as a biological marker for chromium exposure.
Phase I and Pharmacokinetics Trial of ABI-007, a Novel Nanoparticle Formulation of Paclitaxel in Patients With Advanced Nonhematologic Malignancies
Authors: David W. Nyman, Kimberley J. Campbell, Evan Hersh, Kristen Long, Kelly Richardson, Vuong Trieu, Neil Desai, Michael J. Hawkins, Daniel D. Von Hoff
Journal: Journal of Clinical Oncology (2005)

ABI-007 is a novel solvent-free, albumin-bound, 130-nm particle formulation of paclitaxel designed to avoid solvent-related toxicities and to deliver paclitaxel to tumors via molecular pathways involving an endothelial cell-surface albumin receptor (gp60) and an albumin-binding protein expressed by tumor cells and secreted into the tumor interstitium (secreted protein acid rich in cysteine). This study determined the maximum-tolerated dose (MTD) of ABI-007 monotherapy administered weekly (three weekly doses, repeated every 4 weeks) and assessed the pharmacokinetics of paclitaxel administered as ABI-007.Patients with advanced nonhematologic malignancies received ABI-007 without premedication at dose levels from 80 to 200 mg/m(2) as a 30-minute intravenous infusion once a week for 3 weeks, followed by 1 week of rest (one cycle).Thirty-nine patients were treated with an average of five cycles of ABI-007; 33% of patients received > or = six cycles of treatment. MTDs for heavily and lightly pretreated patients were 100 and 150 mg/m(2), respectively; and the dose-limiting toxicities were grade 4 neutropenia and grade 3 peripheral neuropathy, respectively. Maximum paclitaxel concentration and area under the curve increased linearly with dose. Dose-dependent changes in plasma clearance did not occur. Partial responses were observed in five patients with breast, lung, and ovarian cancers, all of whom had previously been treated with paclitaxel containing polyoxyethylated castor oil in the formulation.This study demonstrated that weekly ABI-007 can be administered at doses exceeding those typically used for paclitaxel containing polyoxyethylated castor oil. Pharmacokinetics were linear over the dose range studied. Antitumor responses occurred in patients previously treated with paclitaxel containing polyoxyethylated castor oil.
Ischemia induces partial loss of surface membrane polarity and accumulation of putative calcium ionophores.
Authors: B A Molitoris, P D Wilson, R W Schrier, F R Simon
Journal: Journal of Clinical Investigation (1985)

To determine if ischemia induces alterations in renal proximal tubule surface membranes, brush border (BBM) and basolateral membranes (BLM) were isolated simultaneously from the same cortical homogenate after 50 min of renal pedicle clamping. Ischemia caused a selective decrease in the specific activity of BBM marker enzymes leucine aminopeptidase and alkaline phosphatase, but did not effect enrichment (15 times). Neither specific activity nor enrichment (10 times) of BLM NaK-ATPase was altered by ischemia. Contamination of BBM by intracellular organelles was also unchanged, but there was an increase in the specific activity (41.1 vs. 60.0, P less than 0.01) and enrichment (2.3 vs. 4.3, P less than 0.01) of NaK-ATPase in the ischemic BBM fraction. Ischemia increased BLM lysophosphatidylcholine (1.3 vs. 2.5%, P less than 0.05) and phosphatidic acid (0.4 vs. 1.3%, P less than 0.05). Ischemia also decreased BBM sphingomyelin (38.5 vs. 29.6%, P less than 0.01) and phosphatidylserine (16.1 vs. 11.4%, P less than 0.01), and increased phosphatidylcholine (17.2 vs. 29.7%, P less than 0.01), phosphatidylinositol (1.8 vs. 4.6%, P less than 0.01), and lysophosphatidylcholine (1.0 vs. 1.8%, P less than 0.05). The large changes in BBM phospholipids did not result from new phospholipid synthesis, since the specific activity (32P dpm/nmol Pi) of prelabeled individual and total phospholipids was unaltered by ischemia. We next evaluated if these changes were due to inability of ischemic cells to maintain surface membrane polarity. Cytochemical evaluation showed that while NaK-ATPase could be detected only in control BLM, specific deposits of reaction product were present in the BBM of ischemic kidneys. Furthermore, using continuous sucrose gradients, the enzymatic profile of ischemic BBM NaK-ATPase shifted away from ischemic BLM NaK-ATPase and toward the BBM enzymatic marker leucine aminopeptidase. Taken together, these data suggest that NaK-ATPase activity determined enzymatically and cytochemically was located within ischemic BBM. We propose that ischemia impairs the ability of cells to maintain surface membrane polarity, and also results in the accumulation of putative calcium ionophores.
Transmission of Hepatitis C Virus
Authors: R. Stefan Ross, Michael Roggendorf
Journal: New England Journal of Medicine (2001)

The article by Mechanic et al. (Jan.18 issue) 1 challenges the prevailing wisdom that the increased penetration of managed care is associated with a decrease in the length of patients' office visits with physicians.The data to support their conclusions were derived from the National Ambulatory Medical Care Survey (NAMCS) and the monitoring system of the American Medical Association (AMA).Although the numbers superficially suggest that more time is being spent with patients, no measure of the time physicians actually spent talking with and examining patients could be obtained from these studies.Although there may have been an "upward trend in the length of visits for both primary and specialty care," I would suggest that the apparent increase in duration may be accounted for by the time spent in the completion of paperwork.If such a study were performed in academic medical centers, such as the one in which I practice, it would find a dramatic increase in the time physicians spend documenting, and frequently duplicating, the work and findings of trainees.As pediatricians, we espouse emphasizing the quality, not the quantity, of parents' time with children.We should do the same for physicians' time with patients.
Double reflux: double trouble
Authors: M F VAEZI, J E RICHTER
Journal: Gut (1999)

See article on page 598 

The noxious agents responsible for injuring the oesophageal mucosa in patients with gastro-oesophageal reflux disease (GORD) may originate from two possible sources, the stomach and the duodenum. Hydrochloric acid and pepsin are the important gastric contents, whereas conjugated and unconjugated bile acids and trypsin are the proposed duodenal ingredients predisposing to the development of oesophageal symptoms and mucosal injury.1 The regurgitation of these duodenal contents into the stomach followed by reflux into the oesophagus is known as duodenogastro-oesophageal reflux (DGOR).

To date, the controversy in the literature regarding the specific agents responsible for oesophageal damage centres around the relative importance of acid/pepsin reflux versus DGOR. Early animal studies have clearly shown that acid alone, and in combination with various pepsin concentrations, is damaging to the oesophagus.2-5 For example, Goldberg and colleagues2 showed oesophageal mucosal damage in the intact feline oesophagus with either very high acid concentrations (pH 1.0–1.3) or lower acid concentrations (pH 1.6–2.0) in the presence of pepsin. Additionally, human studies3-5 have clearly delineated a positive correlation between the degree of abnormal acid reflux and the severity of oesophagitis. These studies show that more than 90% of patients with oesophagitis and Barrett’s oesophagus have increased oesophageal exposure to acid on pH monitoring.5 Additionally, Bremner and colleagues6 observed that patients with increased oesophageal exposure to pH 1–2, corresponding to the known pKa of pepsin, had the most significant degrees of oesophagitis; an indirect inference to the possible importance of pepsin. Therefore, the role of acid and pepsin in causing oesophageal mucosal injury is irrefutable.

The role of duodenal contents in the development of oesophageal mucosal injury is controversial and the subject of many animal and human studies. Animal studies show that oesophageal mucosal damage caused by bile acids is …
Government is accused of back-pedalling on its commitment to "parity of esteem" between mental and physical healthcare
Authors: M. Limb
Journal: BMJ (2014)

Experts have warned that “discriminatory” funding cuts are damaging mental healthcare in England.

Sue Bailey, president of the Royal College of Psychiatrists, speaking at a conference in London on Tuesday 29 April organised by the Westminster Health Forum, denounced new changes to tariffs that differentially affect mental and physical health services.

She was referring to an announcement earlier this year by NHS England and Monitor that recommended smaller cuts in the tariff for acute care trusts than for other types of trust in 2014-15.1 The healthcare bodies argued that hospitals would incur “extra” costs to implement …
Chemotherapy for Child with Positive Tuberculin Reaction
Authors: William Weiss
Journal: JAMA (1961)

<h3>To the Editor:—</h3> Dr. Robert B. Clark, III, takes issue (<i>JAMA</i><b>176:</b>73 [April 8] 1961) with a statement that children under 4 years of age "should be given 5 mg. of isoniazid per kilogram of body weight per day for one year or more," which appeared in the answer to the question concerning chemotherapy for a child with a positive tuberculin reaction (<i>JAMA</i><b>175:</b>74 [Jan. 7] 1961). Dr. Clark feels that the dosage of isoniazid should be 3 times as high, and that paraaminosalicylic acid (PAS) should be given because many children inactivate isoniazid rapidly, and these 2 procedures would insure that rapid inactivators get adequate isoniazid therapy. He further recommends that it would be preferable to measure the serum level of active isoniazid after test doses and adjust the dose to produce an active isoniazid level higher than 0.4 mcg. per milliliter 6 hours after the dose.
The influence of hormonal status and features of the metabolic syndrome on bone density: A population-based study of Swedish women aged 50 to 59 years. The women's health in the Lund area study
Authors: Jonas Lidfeldt, Lydia Holmdahl, G[ouml ]ran Samsioe, Christina Nerbrand, Per Nyberg, Bengt Scherst[eacute]n, Carl-David Agardh
Journal: Metabolism (2002)
Three-dimensional ultrastructural study of molluscum contagiosum in the skin using scanning-electron microscopy
Authors: M. MIHARA
Journal: British Journal of Dermatology (1991)

The three-dimensional ultrastructure of molluscum contagiosum virus (MCV) in human skin was visualized using scanning-electron microscopy with the osmium-dimethyl sulphoxide-osmium method. There were spherical, ellipsoidal, brick-shaped, miniature and incomplete forms of MCV. In all the forms the surface had densely distributed small protrusions and all had the same ultrastructure. All the forms had one or two long cord-like substances that appeared to be linked together, but became short, vestigial or absent on the surface of the mature virus. The cord-like substances were connected to the core of the MCV. In the matrix between the viruses, the cord-like substances formed an intricate fine network.
B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation
Authors: Bernd Jahrsdörfer, Sue E. Blackwell, James E. Wooldridge, Jian Huang, Melinda W. Andreski, Laura S. Jacobus, Christiana M. Taylor, George J. Weiner
Journal: Blood (2006)
Ozone and Survival in Four Cohorts with Potentially Predisposing Diseases
Authors: Antonella Zanobetti, Joel Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Time series studies have reported associations between ozone and daily deaths. Only one cohort study has reported the effect of long-term exposures on deaths, and little is known about effects of chronic ozone exposure on survival in susceptible populations.We investigated whether ozone was associated with survival in four cohorts of persons with specific diseases in 105 United States cities, treating ozone as a time varying exposure.We used Medicare data (1985–2006), and constructed cohorts of persons hospitalized with chronic conditions that might predispose to ozone effects: chronic obstructive pulmonary disease, diabetes, congestive heart failure, and myocardial infarction. Yearly warm-season average ozone was merged to the individual follow-up in each city. We applied Cox proportional hazard model for each cohort within each city, adjusting for individual risk factors, temperature, and city-specific long-term trends.We found significant associations with a hazard ratio for mortality of 1.06 (95% confidence interval [CI], 1.03–1.08) per 5-ppb increase in summer average ozone for persons with congestive heart failure; of 1.09 (95% CI, 1.06–1.12) with myocardial infarction; of 1.07 (95% CI, 1.04–1.09) with chronic obstructive pulmonary disease; and of 1.07 (95% CI, 1.05–1.10) for diabetics.We also found that the effect varied by region, but that this was mostly explained by mean temperature, which is likely a surrogate of air conditioning use, and hence exposure.This is the first study that follows persons with specific chronic conditions, and shows that long-term ozone exposure is associated with increased risk of death in these groups.
Irritable urethral syndrome: follow up study in general practice.
Authors: T C O'Dowd, R Pill, J E Smail, R H Davis
Journal: BMJ (1986)

Two years after a microbiological study of the urethral syndrome 25 of 31 women had had further symptoms, but only two had sought medical help for their symptoms in the year after the study. Analysis of patients9 records showed that women with the urethral syndrome had higher consultation and sterilisation rates and more psychosomatic symptoms and relationship problems than matched control patients. Using the Nottingham health profile women with the urethral syndrome were more likely to mention that health problems affected their sex lives and were more likely to see themselves as having health problems than control patients. Women who have the urethral syndrome are considerable drain on the doctor9s time, and management needs to be directed towards the anxious patient who makes such demands. Seeing the condition as the "irritable urethral syndrome" may help both doctor and patient to recognize the psychosomatic aspect of the problem.
Progressive obstructive lung disease associated with microscopic polyangiitis.
Authors: O Brugiere, O Raffy, C Sleiman, O Groussard, E Rothchild, F Mellot, G Jebrak, H Mal, C Roue, R Pariente, M Fournier
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Small airway involvement and progressive severe airflow obstruction are unexpected features in patients with microscopic polyangiitis. We report the case of a patient with microscopic polyangiitis and circulating anti-neutrophil cytoplasmic antibodies (ANCA), who developed pulmonary hyperinflation and airflow obstruction over a 7-yr period. Systemic manifestations of this vasculitis improved under corticosteriods and cyclophosphamid therapy, a treatment that did not influence either the very high level of anti-myeloperoxidase antibodies or the ventilatory impairment. Small airway involvement was suspected on the basis of pathologic small airway lesions and a mild emphysematous pattern on computed tomography (CT) scan, which was out of proportion with the severity of the obstructive lung disease.
Monitoring Hepatic Artery Spasm for Chemotherapeutic Infusion by Using Tc-99m Labeled Macroaggregated Albumin
Authors: C J TULA, A G BLEDIN, C S SOO, T P HAYNIE
Journal: Clinical Nuclear Medicine (1983)

During angiographic placement of an intra-arterial hepatic catheter, a spasm was encountered in the proper hepatic artery. Subsequent angiography, however, revealed normal arteries. Tc-99m MAA intra-arterial infusion was then performed which showed a hepatic artery spasm. Twenty-four hours after the initial hepatic arterial spasm, a repeat injection of Tc-99m MAA revealed that the spasm was no longer present and, therefore, that intra-arterial chemotherapy could be administered.