tbuckley/cabot-search huggingface dataset:
Increase of lymphocytes bearing the gamma/delta T cell receptor in the jejunum of patients with dermatitis herpetiformis.
Authors: E Savilahti, T Reunala, M Maki
Journal: Gut (1992)

The densities of T cells and of cells bearing the T cell receptors gamma/delta and alpha/delta and the surface antigens CD4 and CD8 in jejunal specimens from 21 patients with dermatitis herpetiformis were compared with those in specimens from 13 untreated adults with coeliac disease and 13 control subjects. In the lamina propria of the jejunum the median density of gamma/delta+ cells was significantly (p less than 0.001) greater in untreated patients with dermatitis herpetiformis than in control subjects (114 v 36 cells/mm2) and similar to that found in the patients with coeliac disease (115 cells/mm2). The difference in gamma/delta+ cell density between patients with dermatitis herpetiformis and control subjects was much greater in the surface epithelium of the jejunum: the median density for 14 untreated patients with dermatitis herpetiformis was 39 cells/mm, for seven patients with dermatitis herpetiformis on a gluten free diet 34 cells/mm, and for control subjects 2 cells/mm; the coeliac patients had the same density as the patients with dermatitis herpetiformis (45 cells/mm). The higher density of cells bearing the alpha/delta T cell receptor in the epithelium (median 77 cells/mm) of untreated patients with dermatitis herpetiformis was associated with a gluten containing diet; in specimens taken from patients with dermatitis herpetiformis on a gluten free diet the median density was similar to that in the control subjects (44 v 39 cells/mm). The increase in the number of lymphocytes bearing the T cell receptor gamma/delta, particularly in the epithelium of the jejunum, seems to be a constant marker for these closely related diseases, whereas the density of alpha/delta+ T cells is dependent on the diet.
METABOLIC STUDIES WITH A NEW SERIES OF 1,4-DIENE STEROIDS. II. EFFECTS IN NORMAL SUBJECTS OF PREDNISONE, PREDNISOLONE, AND 9α-FLUOROPREDNISOLONE*
Authors: Maurice M. Pechet, Blair Bowers, Frederic C. Bartter
Journal: Journal of Clinical Investigation (1959)

1,2-Dehydrogenation of 21-carbon steroids pos- sessing an oxygen function at carbons 11, 17 and 21 (cortisone and cortisol) results in an enhance- ment of anti-anabolic or catabolic and anti-inflam- matory properties in Addisonian subjects (2).* Part of this material has been presented previously (1).The names "metacortandracin" and "metacortandra- lone" have since been replaced by "prednisone" and "prednisolone." 3 /22 / 54 PREDNISOLONE J-B 22 cr AMYLOID GOITER 6C BuG /24 HR 00-19-69 E Fecol (I m) GM /24 HR Urinary I2~~~~~~~~~~~~~~~~~~1 2ilThe present study was undertaken to extend these observations to normal subjects and to delineate further the effects of these steroids, in very large doses, on the constituents of protoplasm.
Steroidogenic Acute Regulatory Protein (StAR): Evidence of Gonadotropin-Induced Steroidogenesis in Alzheimer Disease
Authors: Kate M Webber, Douglas M Stocco, Gemma Casadesus, Richard L Bowen, Craig S Atwood, Laura A Previll, Peggy LR Harris, Xiongwei Zhu, George Perry, Mark A Smith
Journal: Molecular Neurodegeneration (2006)

Abstract Background Alzheimer disease (AD) is clinically characterized by progressive memory loss, impairments in behavior, language and visual-spatial skills and ultimately, death. Epidemiological data reporting the predisposition of women to AD has led to a number of lines of evidence suggesting that age-related changes in hormones of the hypothalamic-pituitary-gonadal (HPG) axis following reproductive senescence, may contribute to the etiology of AD. Recent studies from our group and others have reported not only increases in circulating gonadotropins, namely luteinizing hormone (LH) in individuals with AD compared with control individuals, but also significant elevations of LH in vulnerable neuronal populations in individuals with AD compared to control cases as well as the highest density of gonadotropin receptors in the brain are found within the hippocampus, a region devastated in AD. However, while LH is higher in AD patients, the downstream consequences of this are incompletely understood. To begin to examine this issue, here, we examined the expression levels of steroidogenic acute regulatory (StAR) protein, which regulates the first key event in steroidogenesis, namely, the transport of cholesterol into the mitochondria, and is regulated by LH through the cyclic AMP second messenger pathway, in AD and control brain tissue. Results Our data revealed that StAR protein was markedly increased in both the cytoplasm of hippocampal pyramidal neurons as well as in the cytoplasm of other non-neuronal cell types from AD brains when compared with age-matched controls. Importantly, and suggestive of a direct mechanistic link, StAR protein expression in AD brains colocalized with LH receptor expression. Conclusion Therefore, our findings suggest that LH is not only able to bind to its receptor and induce potentially pathogenic signaling in AD, but also that steroidogenic pathways regulated by LH may play a role in AD.
Radiologic Examination of the Orohypopharynx and Esophagus
Authors: D. A. W. Edwards
Journal: Gut (1979)

such as De-Ritis ratio and the TGR.These are used descriptively without any detailed discussion of the origin of the enzyme, its specificity, or even its name: all enzymes are referred to by initialsfor example, GOT, CHE, GLDH.The assumption of familiarity with these abbreviations may be correct for the continental reader, but is likely to be received with dismay in this English translation aimed at the British and American markets.The book should prove useful to a British physician wanting to assess the value of laparoscopy.Its price may deter others from purchasing it even for their library.
Oral montelukast in acute asthma exacerbations: a randomised, double-blind, placebo-controlled trial
Authors: C. F. Ramsay, D. Pearson, S. Mildenhall, A. M. Wilson
Journal: Thorax (2010)

Although leukotriene receptor antagonists have an established role in the management of patients with chronic asthma, their efficacy in an acute asthma exacerbation is not fully known.87 adults with acute asthma requiring hospitalisation were randomly assigned to receive either montelukast 10 mg or placebo on admission and every evening thereafter for 4 weeks (when they were reviewed as outpatients). All patients were admitted under the care of a consultant chest physician and received full care for acute asthma according to the British Thoracic Society guidelines. The primary end point was the difference in peak expiratory flow (PEF) between active and placebo treatment the morning following admission.Primary end point data were analysed for 73 patients. At study entry, patients who received montelukast (n=37) had a mean (±SD) PEF of 227.6 (±56.9) l/min (47.6% predicted) and those who received placebo (n=36) had a PEF of 240.3 (±99.8) l/min (49.6% predicted). The morning after admission, patients who received montelukast achieved a PEF of 389.6 (±109.7) l/min (81.4% predicted) compared with 332.3 (±124.9) l/min (69.8% predicted) for placebo (p=0.046). The mean difference between treatment groups was 57.4 l/min (95% CI of 1.15 to 113.6 l/min or 1.95-21.2% predicted).In acute asthma exacerbations the additional administration of oral montelukast results in a significantly higher PEF the morning after admission than that achievable with current standard treatment. Clinical trial number NCT01011452.
LISTER AND FRACTURES
Authors: A. E. Maylard
Journal: BMJ (1922)

Marriages and Births.The marriage rate for 1921 was 11.0 per 1,000 of the population, a figure wbiclh justifies tlhn Medical Officer's com- ment " tlhe posb-war booin in marriages has -subsided," a comment wlhioh can be extended to Glasgow (10.7), to Dundee (10.0), and to Aberdeen (11.0).There was also signs of a subsidence in the post-war boom in babies, so to say, for the birtlh rate (corrected) for the extended city fell to 21.5 in 1921, lhavinig been 24.7 in the preceding year.Thie percentage of illegitimnate to total births was 7.2 as compared witlh 7.1 for the whlole of Scotland.Tlle birtlh-rate of Edinburglh was lower thau tlhat of the seven other large to,wns and of Scotland as a wlhole (25.2); its illegitimate birtlh rate was lower tlhan that of Aberdeen and Dundee, but higler than that of Glasgow.
Ginkgo for Memory Enhancement
Authors: Paul R. Solomon, Felicity Adams, Amanda Silver, Jill Zimmer, Richard DeVeaux
Journal: JAMA (2002)

Context Several over-the-counter treatments are marketed as having the ability to improve memory, attention, and related cognitive functions in as little as 4 weeks.These claims, however, are generally not supported by well-controlled clinical studies.Objective To evaluate whether ginkgo, an over-the-counter agent marketed as enhancing memory, improves memory in elderly adults as measured by objective neuropsychological tests and subjective ratings.Design Six-week randomized, double-blind, placebo-controlled, parallel-group trial.Setting and Participants Community-dwelling volunteer men (n=98) and women (n=132) older than 60 years with Mini-Mental State Examination scores greater than 26 and in generally good health were recruited by a US academic center via newspaper advertisements and enrolled over a 26-month period from July 1996 to September 1998.Intervention Participants were randomly assigned to receive ginkgo, 40 mg 3 times per day (n=115), or matching placebo (n=115). Main Outcome MeasuresStandardized neuropsychological tests of verbal and nonverbal learning and memory, attention and concentration, naming and expressive language, participant self-report on a memory questionnaire, and caregiver clinical global impression of change as completed by a companion. ResultsTwo hundred three participants (88%) completed the protocol.Analysis of the modified intent-to-treat population (all 219 participants returning for evaluation) indicated that there were no significant differences between treatment groups on any outcome measure.Analysis of the fully evaluable population (the 203 who complied with treatment and returned for evaluation) also indicated no significant differences for any outcome measure. ConclusionsThe results of this 6-week study indicate that ginkgo did not facilitate performance on standard neuropsychological tests of learning, memory, attention, and concentration or naming and verbal fluency in elderly adults without cognitive impairment.The ginkgo group also did not differ from the control group in terms of selfreported memory function or global rating by spouses, friends, and relatives.These data suggest that when taken following the manufacturer's instructions, ginkgo provides no measurable benefit in memory or related cognitive function to adults with healthy cognitive function.
An Underrecognized Challenge in Evaluating Postmarketing Drug Safety
Authors: Dan M. Roden
Journal: Circulation (2005)

he withdrawal of the cyclooxygenase (COX)-2-specific inhibitor rofecoxib (Vioxx; Merck) has generated a high-profile debate in the medical and lay press over when a signal suggesting the potential for harm from this drug was first apparent and what steps the medical community, the US Food and Drug Administration, and the pharmaceutical sponsor took and should have taken to address this issue. 1,2This debate, however, has glossed over a fundamental problem that the withdrawal of the drug serves to highlight-not how best to deal with a potential signal once it is described, but rather how to identify such important and initially unanticipated effects after a drug is marketed. What Is Known About a Drug WhenIt Is Marketed?The contemporary processes of drug discovery and marketing include both basic studies and drug exposure in humans, generally in no more than several thousand patients.These studies establish a putative mechanism of action of the new compound, although, as discussed below, new molecular mechanisms of actions often are discovered after a drug has been marketed.Efficacy must be established in rigorous controlled clinical trials, with well-defined patient populations, inclusion and exclusion criteria, predefined end points, and appropriate statistical analyses.Other important pieces of information include major mechanisms of drug metabolism and excretion and the potential for both pharmacokinetic and pharmacodynamic drug interactions.An important result of this premarketing workup is that adverse effects that commonly occur during the administration of a drug become well recognized.If these effects are common or serious, then the drug may in fact not be suitable for marketing.
Phagocytosis of Legionella pneumophila is mediated by human monocyte complement receptors.
Authors: N R Payne, M A Horwitz
Journal: The Journal of Experimental Medicine (1987)

We have examined receptors mediating phagocytosis of the intracellular bacterial pathogen, Legionella pneumophila. Three mAbs against the type 3 complement receptor (CR3), which recognizes C3bi, inhibit adherence of L. pneumophila to monocytes by 64 +/- 8% to 74 +/- 11%. An mAb against the type 1 complement receptor (CR1), which recognizes C3b, inhibits adherence by 68 +/- 1%. mAbs against other monocyte surface antigens do not significantly influence adherence. Monocytes plated on substrates of L. pneumophila membranes modulate their CR1 and CR3 receptors but not Fc receptors; such monocytes bind 70% fewer C3b-coated erythrocytes and 53% fewer C3bi-coated erythrocytes than control monocytes. Adherence of L. pneumophila to monocytes in nonimmune sera is dependent on heat-labile serum opsonins; adherence is markedly reduced in heat-inactivated serum (84% reduction) or buffer alone (97% reduction) compared with fresh serum. mAbs against CR1 and CR3 receptors also inhibit L. pneumophila intracellular multiplication and protect monocyte monolayers from destruction by this bacterium. This study demonstrates that human monocyte complement receptors, CR1 and CR3, mediate phagocytosis of L. pneumophila. These receptors may play a general role in mediating phagocytosis of intracellular pathogens.
Clinical presentation of patients with "dyspepsia". Detailed symptomatic study of 360 patients.
Authors: J C Horrocks, F T De Dombal
Journal: Gut (1978)

This paper describes the clinical presentation of 360 patients suffering from "dyspepsia" at the time of their initial visit to two hospitals in Yorkshire. Disease categories studied were cholecystitis, duodenal ulcer, gastric ulcer, gastric cancer, and "functional" dyspepsia, with at least 50 patients in each category. The findings of this series are contrasted with "textbook" descriptions of these conditions. Some contrasts are quite surprising-for example, most of the 360 patients claimed that their pain was not aggravated by food. It is suggested that one reason for diagnostic error in this area of medicine is that clinicians have a faulty mental "database" of information with regard to the presentation of the various diseases concerned.
Pulmonary Rapidly Adapting Receptor Stimulation Does Not Increase Airway Resistance in Anesthetized Rabbits
Authors: JERRY YU, JU F. ZHANG, ANDREW M. ROBERTS, LYNELL C. COLLINS, EUGENE C. FLETCHER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

In open-chest artificially ventilated rabbits, removal followed by replacement of positive end-expiratory pressure (PEEP maneuver) favors stimulation of airway rapidly adapting receptors (RARs). The purpose of the present study was to determine whether activation of RARs can cause bronchoconstriction. We measured airway pressure, airflow, and tidal volume, and calculated dynamic lung compliance and total lung resistance. PEEP maneuver increased airway pressure swings (16.4 ± 4% above control; p = 0.0016) and decreased compliance (to 84.8 ± 2.8% of control; p = 0.0002) without changing resistance (108.0 ± 4.4% of control; p = 0.85). On the other hand, the resistance increased greatly (93 ± 13%, p < 0.01) after intravenous injection of acetylcholine or electrical stimulation of vagal efferents, indicating that our system could detect increases in the resistance. In a separate group, we stimulated RARs by stroking the trachea with a cotton tip (tickling), tickling produced cough, manifested by increased pressure and flow without resistance changing. These changes were abolished after paralysis with succinylcholine. Because we did not detect an increase in airflow resistance during activation of RARs by the PEEP maneuver and tickling, we conclude that increase in resistance may not be an important reflex component of airway RARs.
Novel SN-38–Incorporated Polymeric Micelle, NK012, Strongly Suppresses Renal Cancer Progression
Authors: Makoto Sumitomo, Fumiaki Koizumi, Takako Asano, Akio Horiguchi, Keiichi Ito, Tomohiko Asano, Tadao Kakizoe, Masamichi Hayakawa, Yasuhiro Matsumura
Journal: Cancer Research (2008)

Abstract It has been recently reported that NK012, a 7-ethyl-10-hydroxy-camptothecin (SN-38)–releasing nanodevice, markedly enhances the antitumor activity of SN-38, especially in hypervascular tumors through the enhanced permeability and retention effect. Renal cell carcinoma (RCC) is a typical hypervascular tumor with an irregular vascular architecture. We therefore investigated the antitumor activity of NK012 in a hypervascular tumor model from RCC. Immunohistochemical examination revealed that Renca tumors contained much more CD34-positive neovessels than SKRC-49 tumors. Compared with CPT-11, NK012 had significant antitumor activity against both bulky Renca and SKRC-49 tumors. Notably, NK012 eradicated rapid-growing Renca tumors in 6 of 10 mice, whereas it failed to eradicate SKRC-49 tumors. In the pulmonary metastasis treatment model, an enhanced and prolonged distribution of free SN-38 was observed in metastatic lung tissues but not in nonmetastatic lung tissues after NK012 administration. NK012 treatment resulted in a significant decrease in metastatic nodule number and was of benefit to survival. Our study shows the outstanding advantage of polymeric micelle-based drug carriers and suggests that NK012 would be effective in treating disseminated RCCs with irregular vascular architectures. [Cancer Res 2008;68(6):1631–5]
The endothelin system in pulmonary arterial hypertension
Authors: N GALIE
Journal: Cardiovascular Research (2004)

Endothelin-1 (ET-1), a peptide produced primarily by vascular endothelial cells, was discovered in 1980 and it was characterized as a powerful vasoconstrictor and mitogen for smooth muscle. ET-1 binds to two types of receptors, ETA and ETB: ETA-receptors are found in smooth muscle cells, whereas ETB-receptors are localized on both endothelial cells and in smooth muscle cells. Activation of ETA- and ETB-receptors on smooth muscle cells mediates the vasoconstrictive and mitogenic effects of ET-1. Stimulation of endothelial ETB-receptors promotes ET-1 clearance and activation of NO and prostacyclin release. Pulmonary arterial hypertension (PAH) is a severe condition characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death. An activation of the ET-1 system has been demonstrated in both plasma and lung tissues of PAH patients as well as in animal models of PAH. The most efficient way to antagonize the ET-1 system is the use of ET-1 receptor antagonists that can block either ETA- or ETA- and ETB-receptors. These drugs are effective in animal models of PAH and have been tested in multiple clinical trials in patients with PAH. Bosentan, an orally active, dual ET-1 receptor antagonist has been shown to improve symptoms, exercise capacity, hemodynamics, echocardiographic parameters and the outcome of patients with severe PAH, and it has been approved for clinical use in many countries. The selective ETA-receptor antagonist sitaxentan has improved exercise capacity and hemodynamics of PAH patients in two preliminary studies. The main side effect of ET-1 antagonists is the increase of liver enzymes likely due to an accumulation of bile salts cytotoxic to hepatocytes. Additional trials with these drugs are currently ongoing. In conclusion, the hypothesis that the ET-1 system over-activation can be successfully antagonised in patients with PAH has been clearly demonstrated.
VITAMIN B12Co60 READILY PASSES THE PLACENTA INTO FETAL ORGANS AND NURSING PROVIDES B12 FROM MOTHER TO PUP
Authors: W. D. Woods, W. B. Hawkins, G. H. Whipple
Journal: The Journal of Experimental Medicine (1960)

The placenta is permeable to B(12)Co(60). Together with salts, sugar, amino acids, vitamins, and proteins, the B(12) is contributed to the growing embryos from the mother's body stores. At birth, the placenta contains a liberal amount of B(12), which the mother regains by ingestion of the placentas. Nursing draws a liberal amount of B(12)Co(60) from the mother's stores and contributes it to the body of the pups where it is absorbed and distributed in the various organs, much as noted when adult dogs are injected with B(12)Co(60). A redistribution is noted as the months pass; but the high values in the heart, liver, and gastric mucosa persist, and the brain usually shows a slow increase. Enterohepatic circulation of B(12) may involve bile and enteric content plus hepatic, gastric, and pancreatic epithelial secretion. This type of body recycling of radioactive B(12) is discussed but not proven. High values of B(12) in the heart, brain, gastric mucosa, and liver indicate that the vitamin is functionally active, not an inert fraction.
iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human
Authors: Daniele Bergamaschi, Yardena Samuels, Nigel J. O'Neil, Giuseppe Trigiante, Tim Crook, Jung-Kuang Hsieh, Daniel J. O'Connor, Shan Zhong, Isabelle Campargue, Matthew L. Tomlinson, Patricia E. Kuwabara, Xin Lu
Journal: Nature Genetics (2003)
Distribution of the Coronary Blood Flow across the Canine Heart Wall during Systole
Authors: JAMES M. DOWNEY, EDWARD S. KIRK
Journal: Circulation Research (1974)

The transmural distribution of left coronary blood flow during systole was studied by measuring the myocardial uptake of a bolus of 86 Rb introduced into the coronary circulation when the perfusion was limited to the periods of systole. The measurement revealed a transmural gradient of systolic blood flow with a flow rate in the outer fourth of the left ventricle about twice that in the inner fourth. A gradient of flow encompassing all depths of myocardial tissue revealed that intramyocardial pressure during systole was not sufficient to completely collapse the vessels and, therefore, did not exceed intraventricular pressure. The results of this experiment indicate that intramyocardial pressure limits coronary blood flow through a vascular sluice mechanism.