tbuckley/cabot-search huggingface dataset:
CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras andjunD
Authors: Fotini Nicolaou, Jens M. Teodoridis, Heiyoung Park, Alexander Georgakis, Omid C. Farokhzad, Erwin P. Böttinger, Nicolas Da Silva, Philippe Rousselot, Christine Chomienne, Katalin Ferenczi, M. Amin Arnaout, C. Simon Shelley
Journal: Blood (2003)
PRESIDENT W. H. HARRISON DID NOT PRACTICE MEDICINE
Authors: George J. Garceau
Journal: JAMA (1960)

To the Editor:—  InThe Journal, May 21, page 296, it is stated, No president of the United States has had a medical background. May I suggest that staff ofThe Journaldo a bit of research on the background of William Henry Harrison (1773 to 1841), ninth president of the United States. I believe they will find that President Harrison practiced medicine for a short while. I have forgotten the facts relative to his activities as a medical man, although I believe he acted as a combination line officer and medical officer in the Indian Wars in Indiana.
Survey of Blood Bank Physicians and Medical Directors
Authors: John A. Shively
Journal: JAMA (1971)

In a survey of blood bank physicians and medical directors in the United States conducted by the Scientific Advisory Committee of the American Association of Blood Banks, 980 (47%) of the 2,099 questionnaires were returned, with the majority of respondents being pathologists. Many of the blood bank physicians had received multiple specialty training as well as a master's or second doctorate degree. A relatively large segment received portions of their training via seminars and postgraduate courses. A number had no specialty certification with a smaller group having multiple or subspecialty certification. Specific and sustained graduate medical education programs and a mechanism for recognition should be developed for blood bank physicians and potential directors of blood banks and transfusion services.
Reducing emergency presentations of cancer patients remains a challenge, says cancer tsar
Authors: P. Dinsdale
Journal: BMJ (2012)

Late diagnosis and treatment of cancer in England remains one of the biggest challenges in reducing the 10 000 deaths that could be avoided if the country’s cancer treatment matched the best in European countries, the government’s cancer tsar has said.

Speaking at a conference on cancer treatment in Europe organised by the European Union and member states, Mike Richards said that his unit’s work was currently focusing on why so many patients were presenting as emergencies to cancer specialists and, as a result, had a reduced chance of recovery.

Around a quarter of new cancer cases are currently in people who present to doctors as “emergencies,” and the cancer tsar’s unit, set up as part of the national cancer plan, is studying the reasons why the figure is still so high.

“There is a big problem of …
Paradoxical Effect of Increased Diastolic Ca <sup>2+</sup> Release and Decreased Sinoatrial Node Activity in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Patricia Neco, Angelo G. Torrente, Pietro Mesirca, Esther Zorio, Nian Liu, Silvia G. Priori, Carlo Napolitano, Sylvain Richard, Jean-Pierre Benitah, Matteo E. Mangoni, Ana María Gómez
Journal: Circulation (2012)

Background— Catecholaminergic polymorphic ventricular tachycardia is characterized by stress-triggered syncope and sudden death. Patients with catecholaminergic polymorphic ventricular tachycardia manifest sinoatrial node (SAN) dysfunction, the mechanisms of which remain unexplored. Methods and Results— We investigated SAN [Ca 2+ ] i handling in mice carrying the catecholaminergic polymorphic ventricular tachycardia–linked mutation of ryanodine receptor (RyR2 R4496C ) and their wild-type (WT) littermates. In vivo telemetric recordings showed impaired SAN automaticity in RyR2 R4496C mice after isoproterenol injection, analogous to what was observed in catecholaminergic polymorphic ventricular tachycardia patients after exercise. Pacemaker activity was explored by measuring spontaneous [Ca 2+ ] i transients in SAN cells within the intact SAN by confocal microscopy. RyR2 R4496C SAN presented significantly slower pacemaker activity and impaired chronotropic response under β-adrenergic stimulation, accompanied by the appearance of pauses (in spontaneous [Ca 2+ ] i transients and action potentials) in 75% of the cases. Ca 2+ spark frequency was increased by 2-fold in RyR2 R4496C SAN. Whole-cell patch-clamp experiments performed on isolated RyR2 R4496C SAN cells showed that L-type Ca 2+ current ( I Ca,L ) density was reduced by ≈50%, an effect blunted by internal Ca 2+ buffering. Isoproterenol dramatically increased the frequency of Ca 2+ sparks and waves by ≈5 and ≈10-fold, respectively. Interestingly, the sarcoplasmic reticulum Ca 2+ content was significantly reduced in RyR2 R4496C SAN cells in the presence of isoproterenol, which may contribute to stopping the “Ca 2+ clock” rhythm generation, originating SAN pauses. Conclusion— The increased activity of RyR2 R4496C in SAN leads to an unanticipated decrease in SAN automaticity by a Ca 2+ -dependent decrease of I Ca,L and sarcoplasmic reticulum Ca 2+ depletion during diastole, identifying subcellular pathophysiological alterations contributing to the SAN dysfunction in catecholaminergic polymorphic ventricular tachycardia patients.
Responsiveness of Plasma Atrial Natriuretic Factor to Short-Term Changes in Left Atrial Hemodynamics After Percutaneous Balloon Mitral Valvuloplasty
Authors: Howard M. Waldman, Igor F. Palacios, Peter C. Block, Gerard T. Wilkins, Charles J. Homcy, Robert M. Graham, Michael A. Fifer
Journal: Journal of the American College of Cardiology (1988)
Association Between Vitamin D Receptor Genotype and Age of Onset in Juvenile Japanese Patients With Type 1 Diabetes
Authors: Ichiro Yokota, Shigeko Satomura, Seiko Kitamura, Yumiko Taki, Etsuo Naito, Michinori Ito, Kahoru Nisisho, Yasuhiro Kuroda
Journal: Diabetes Care (2002)

Patients With Type 1 Diabetes1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] not only regulates calcium metabolism but also modulates the immune system.Some reports have suggested that 1,25(OH) 2 D 3 helps to prevent the development of type 1 diabetes.The association between the vitamin D receptor (VDR) genotype and susceptibility to type 1 diabetes has been examined, but a definitive conclusion has not yet been reached (1,2).We examined the VDR genotype in juvenile Japanese patients with type 1 diabetes.A total of 108 diabetic patients (41 boys and 67 girls, age of onset 0.4 -18 years with a median age of 8.9) and 120 nonrelated nondiabetic subjects were studied.Three polymorphic restriction fragment-length polymorphisms (RFLPs), i.e., Fok I, ApaI, and TaqI, were genotyped by PCR-RFLP method.The genotype or allele frequencies were compared statistically by the 2 test.The significance of differences in each genotype for the age of onset was tested with the Mann-Whitney U test.Among the patients, the FF (n ϭ 50) and tt (n ϭ 5) genotypes were found relatively frequently, and aa (n ϭ 46) was infrequent compared with those in control subjects, but these differences were not statistically significant (P ϭ 0.14, 0.18, and 0.38 for FF, tt, and aa genotypes, respectively).There was also no significant difference in the allele frequency of each polymorphism, although the incidence of the F allele tended to be higher in the diabetic patients (P ϭ 0.051).Concerning the age of onset of diabetes, patients with the ff genotype (n ϭ 12, median 5.2 years, range 1.7-11.0)were significantly younger at onset than those with FF (n ϭ 50, 9.7 years, 0.4 -15.9, P ϭ 0.01) or Ff (n ϭ 46, 8.9 years, 0.9 -18.0,P ϭ 0.03).No significant association was observed between the TaqI or ApaI genotype and the age of onset.The ff genotype has been reported to be associated with a lower expression of VDR mRNA and reduced inhibition of phytohemagglutinin-stimulated growth of peripheral blood mononuclear cells.Thus, the Fok I genotype may influence the rate of the progression of insulitis by modifying the autoimmune process, which may have led to the significant difference in the age of onset.The relatively high frequency of the F allele in diabetic patients, which has also been found in Japanese adult diabetic patients (2), is apparently inconsistent with this observation.A possible explanation is that the impact of Fok I polymorphism may not be strong enough to prevent the progression of autoimmune insulitis into overt diabetes and thus does not influence susceptibility to the disease itself.In conclusion, VDR gene polymorphism does not appear to have a strong enough impact to clearly influence susceptibility to the disease itself, but Fok I polymorphism might influence the age of onset of diabetes in juvenile Japanese diabetic patients.
Human biomonitoring: research goals and needs.
Authors: W A Suk, G Collman, T Damstra
Journal: Environmental Health Perspectives (1996)

Epidemiological studies have taken advantage of a number of strategies to monitor human populations for mortality, incidence, and exposure to hazardous environmental agents. These studies have been compromised by the lack of individual exposure assessment data that precisely quantified internal dose. As methods improve in analytical chemistry and molecular biology, direct biological monitoring of exposed populations is possible. Biomarkers have been developed and validated in exposed populations that quantify individual exposure, susceptibility, and early markers of health effects and can be used to study relationships between exposures and environmentally induced diseases. This paper provides background on the state of the art of human populations monitoring and, through a series of case studies, provides examples of novel biomarkers of exposure, susceptibility, and effect that highlight new opportunities for biomonitoring. Prevention of human disease due to environmental contaminants can be accomplished by implementing strategies such as those discussed to monitor exposure and early health effects in human populations.
RESULTS OBTAINED IN THE TRANSMISSION OF DENGUE FEVER
Authors: J. F. SILER
Journal: JAMA (1925)

The Medical Department Research Board of the United States Army and other workers closely associated therewith are investigating a number of the unsolved problems relating to dengue fever, including its etiology, mechanism of transmission by insects, duration of immunity following an attack, and clinical characteristics. The results will be reported fully at a later date, and published in thePhilippine Journal of Science, Bureau of Science, Manila, P. I.  It is our purpose in this summary to present briefly the results of a fairly large series of experiments relating to the transmission of dengue fever by mosquitoes. This work has been done in Manila, during the last few months, from July, 1924, to January, 1925, inclusive.  A total of forty-two American soldiers volunteered for these experiments. Eighty-three biting experiments have been made with potentially infected femaleCulex quinquefasciatus (C. fatigans)andAedes egypti (Stegomyia fasciata), and dengue fever has been
Hospital closures: for good or for ill?
Authors: L. J Donaldson
Journal: BMJ (1997)

BBC 1 Panorama , Monday 6 January BBC Radio 4 The Hospital: a Prognosis , Wednesday 8 January 

The short trailer which preceded the BBC Panorama programme on the health service seemed to promise yet another expose of Britain's NHS: inefficiency and millions of pounds wasted were trumpeted. It was difficult to ignore the inner voice whispering, “Oh no, here it comes again.” Indeed, I found that many health service managers to whom I spoke the next day had reacted the way my generation had in childhood to the introductory theme music to Quatermass . We switched off the set, ran up to bed, and covered our ears with our hands just in case our parents turned it back on again.

Those like myself who started watching Panorama through a crack between their fingers would have done so with growing disbelief. Could it be that the other side of a story that needs to be told would unfold? The programme …
Evaluation of Roentgen Cinedensitometry for Flow Measurement in Models and in the Intact Circulation
Authors: WILHELM RUTISHAUSER, HANSJÖRG SIMON, JEAN PAUL STUCKY, NIKLAUS SCHAD, GIORGIO NOSEDA, JOSEF WELLAUER
Journal: Circulation (1967)

The flow of blood in vitro and in the carotid artery of the dog was calculated by a new cinedensitometric technique and compared with the flow as measured simultaneously by graduated cylinder and stopwatch. Cineangiographic films were projected onto a frosted screen and the light intensity was measured at two neighboring cross sections of the vessel in question. The passage of the contrast medium yielded a pair of indicator-dilution curves of which the difference in mean transit time was calculated. The distance between the cross sections and the diameter of the vessel was measured with the aid of x-ray-dense scales. The flow through the vessel was calculated as the product of cross-sectional area and mean velocity. The correlation coefficient between the volumetric flow and the flow as found by cinedensitometry was 0.976 in vitro and 0.946 in the intact dog with no systematic deviation from the line of identity. The method enables the blood flow in the intact circulation to be calculated in milliliters per second in any vessel that can be clearly visualized by cineangiocardiography.
A randomized clinical trial of ursodeoxycholic acid as adjuvant treatment to prevent liver transplant rejection
Authors: D Barnes, D Talenti, G Cammell, M Goormastic, L Farquhar, M Henderson, D Vogt, J Mayes, M K Westveer, W Carey
Journal: Hepatology (1997)

Acute rejection following orthotopic liver transplantation is a common problem despite current immunosuppressive regimens. Ursodeoxycholic acid (UDCA) has been shown in small, open-labeled studies to prevent rejection episodes, although its effects on complications such as infections, length of hospital stay, and survival have not been evaluated. We conducted a randomized, placebo-controlled, double-blind trial to determine if UDCA (10-15 mg/kg/d) added to a cyclosporine-based immunosuppressive regimen was associated with a decrease in the incidence of at least one episode of acute cellular rejection. Secondary end-points included determining differences in the total number of rejection episodes, the use of muromonab-CD3, the incidence of infections, length of hospital stay, and survival at 90 days and 1 year. Fifty-two patients were randomized, 28 to the treatment group and 24 to the placebo group. During the 3 months of the trial, there was no difference between the placebo and UDCA groups in the number of patients who were rejection-free; however, there were significantly fewer patients in the treatment group who had multiple episodes of acute rejection (0 vs. 6; P = .007). Patients in the treatment group experienced a significantly lower incidence of bacterial infections (4% vs. 29%; P = .02), shorter hospital stay (25 days vs. 34 days; P = .03), and better 90-day survival (100% vs. 83%; P = .04) and 1-year survival (93% vs. 79%). The addition of UDCA to a cyclosporine-based immunosuppressive regimen results in significantly fewer patients experiencing multiple episodes of rejection and improved survival at 90 days and at 1 year. The use of UDCA as adjuvant therapy for patients undergoing liver transplantation who are treated with a cyclosporine-based immunosuppressive regimen should be considered.
Effect of Smoking on the Cardiovascular System of Man
Authors: GRACE M. ROTH, RICHARD M. SHICK
Journal: Circulation (1958)

In normal subjects smoking or the injection of nicotine produces transient vascular effects on the heart and blood vessels. Apparently tobacco angina or tobacco heart is a clinical entity. Abnormal vascular responses after smoking in normal subjects may be due to hypersensitivity to nicotine, such as occurs in tobacco heart, or to the effect of nicotine on a vascular system demonstrated to be hyperreactive by the cold pressor test. Tobacco is one of the most prominent contributing factors in thromboangiitis obliterans, as thromboangiitis is rarely found in nonsmokers. The question as to whether the effects of smoking are due to sudden increased work of the heart or constriction of the coronary artery has stimulated a great amount of research. There is evidence to support both theories. The findings of abnormal ballistocardiograms before and after smoking in the offspring of hypertensive parents and after smoking in the offspring of parents with coronary heart disease are highly important. Statistically coronary artery disease seems to occur more frequently and at an earlier age in the person who smokes much than in the nonsmoker. Likewise, the mortality rate is higher among younger persons with coronary disease who are smokers than among those who are nonsmokers.
Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study
Authors: Natalia Acosta-Baena, Diego Sepulveda-Falla, Carlos Mario Lopera-Gómez, Mario César Jaramillo-Elorza, Sonia Moreno, Daniel Camilo Aguirre-Acevedo, Amanda Saldarriaga, Francisco Lopera
Journal: The Lancet Neurology (2011)
Dependence of the incidence of emphysema on smoking history, age, and sex
Authors: J. A. Anderson, M. S. Dunnill, R. C. Ryder
Journal: Thorax (1972)

The relationship between the incidence of emphysema and smoking history, age, sex, and percentage bronchial mucous gland volume is investigated using the series of necropsy cases reported by Ryder, Dunnill, and Anderson (1971). Using those cases originating from hospital, it is shown that the incidence of emphysema is dependent on smoking history, age, and sex. Percentage bronchial mucous gland volume is not related to emphysema when the three other variables have been allowed for. Thus sex has an effect on the incidence of emphysema over and above the difference between the sexes in the occurrence of smoking. It is also shown that it is reasonable to extrapolate these conclusions from hospital necropsy cases to the general population.
A FOLLOW-UP STUDY OF CHILDREN WITH BEHAVIOR DISORDER AND SYDENHAM'S CHOREA
Authors: W. R. KEELER, LAURETTA BENDER
Journal: American Journal of Psychiatry (1952)

1. A 3-to-15-year follow-up medical, neurological, psychiatric, and social-adjustment study has been conducted on 20 patients who were admitted to the children's ward of the psychiatric division of Bellevue Hospital. 2. The social adjustment and psychiatric outcome of this group of patients were extremely poor. 3. Several cases showed subsequent neurological findings suggestive of a permanent damage or long-continued organic brain disturbance by the rheumatic process. Further investigation in this area must be done before definite conclusions can be drawn. 4. The poor social adjustment and psychiatric outcome appeared to depend upon the interaction of several factors, the relative roles of which can be determined only by future investigation. They were primarily: (1) social and emotional deprivation, (2) pre-existing disease other than the chorea, i.e., encephalitis and schizophrenia, (3) a low IQ, (4) a profound reading disability, (5) a prolonged serious illness that interfered with their normal education and personality development, (6) a possible permanent damage or long-continued organic brain disturbance by the rheumatic process.
Hepatic progenitor cells activation, fibrosis, and adipokines production in pediatric nonalcoholic fatty liver disease
Authors: Valerio Nobili, Guido Carpino, Anna Alisi, Antonio Franchitto, Gianfranco Alpini, Rita De Vito, Paolo Onori, Domenico Alvaro, Eugenio Gaudio
Journal: Hepatology (2012)

Hepatic progenitor cells (HPCs) play a major role in liver repair and regeneration. We evaluated HPC involvement in pediatric nonalcoholic fatty liver disease (pNAFLD). Thirty biopsies of consecutive children and adolescents with untreated NAFLD (19 with nonalcoholic steatohepatitis [NASH] and 11 without NASH) were studied using immunohistochemistry and immunofluorescence. HPCs and HPC-expressing adipokines (e.g., adiponectin, resistin, and glucagon-like peptide 1 [GLP-1]) were counted and correlated with steatosis, inflammation, hepatocyte ballooning, fibrosis, and NAFLD activity score (NAS). The HPC compartment was expanded in pNAFLD, especially in children with NASH, and was independently associated with degree of fibrosis (r = 0.303; P = 0.033). NASH livers were also characterized by increased hepatocyte apoptosis, cell-cycle arrest, and an expanded pool of intermediate hepatocytes. Adiponectin expression in HPCs of pNAFLD patients was down-regulated with respect to the healthy liver, and this expression was inversely correlated with NAS score (r = −0.792; P < 0.001) and steatosis (r = −0.769; P < 0.001). Resistin expression in HPCs increased in pNAFLD and was related to degree of fibrosis (r = 0.432; P < 0.05). GLP-1 was overexpressed in HPCs of pNAFLD patients, and GLP-1 expression was related to degree of steatosis (r = 0.577; P < 0.05) and NAS (r = 0.594; P < 0.01). Conclusions: HPC activation is involved in the response of the liver to oxidative stress in pNAFLD and is correlated with fibrosis and the progression toward NASH. HPCs express adiponectin, resistin, and GLP-1, which become available to resident liver cells and are strongly associated with the severity of NAFLD. These results may have important pathophysiological implications in the modulation of hepatic insulin resistance and the progression of liver injury. (HEPATOLOGY 2012;56:2142–2153)
Crosstalk Between Voltage-Independent Ca <sup>2+</sup> Channels and L-Type Ca <sup>2+</sup> Channels in A7r5 Vascular Smooth Muscle Cells at Elevated Intracellular pH
Authors: Michael Poteser, Ichiro Wakabayashi, Christian Rosker, Margot Teubl, Rainer Schindl, Nikolai M. Soldatov, Christoph Romanin, Klaus Groschner
Journal: Circulation Research (2003)

This study was designed to investigate the role of voltage-independent and voltage-dependent Ca2+ channels in the Ca2+ signaling associated with intracellular alkalinization in A7r5 vascular smooth muscle cells. Extracellular administration of ammonium chloride (20 mmol/L) resulted in elevation of intracellular pH and activation of a sustained Ca2+ entry that was inhibited by 2-amino-ethoxydiphenyl borate (2-APB, 200 micromol/L) but not by verapamil (10 micro;mol/L). Alkalosis-induced Ca2+ entry was mediated by a voltage-independent cation conductance that allowed permeation of Ca2+ (PCa/PNa approximately 6), and was associated with inhibition of L-type Ca2+ currents. Alkalosis-induced inhibition of L-type Ca2+ currents was dependent on the presence of extracellular Ca2+ and was prevented by expression of a dominant-negative mutant of calmodulin. In the absence of extracellular Ca2+, with Ba2+ or Na+ as charge carrier, intracellular alkalosis failed to inhibit but potentiated L-type Ca2+ channel currents. Inhibition of Ca2+ currents through voltage-independent cation channels by 2-APB prevented alkalosis-induced inhibition of L-type Ca2+ currents. Similarly, 2-APB prevented vasopressin-induced activation of nonselective cation channels and inhibition of L-type Ca2+ currents. We suggest the existence of a pH-controlled Ca2+ entry pathway that governs the activity of smooth muscle L-type Ca2+ channels due to control of Ca2+/calmodulin-dependent negative feedback regulation. This Ca2+ entry pathway exhibits striking similarity with the pathway activated by stimulation of phospholipase-C-coupled receptors, and may involve a similar type of cation channel. We demonstrate for the first time the tight functional coupling between these voltage-independent Ca2+ channels and classical voltage-gated L-type Ca2+ channels.