tbuckley/cabot-search huggingface dataset:
Attenuation of Cyclic Nucleotide–Mediated Smooth Muscle Relaxation in Blacks as a Cause of Racial Differences in Vasodilator Function
Authors: Carmine Cardillo, Crescence M. Kilcoyne, Richard O. Cannon, Julio A. Panza
Journal: Circulation (1999)

Vasodilator reactivity is attenuated in normotensive blacks, and this may contribute to their enhanced susceptibility to hypertension and its complications. However, the mechanisms responsible for this phenomenon are unknown. We therefore studied nitric oxide (NO)-dependent and -independent vasorelaxation in healthy blacks and whites to investigate the nature of racial differences in vasodilator function.Forearm flow responses to intra-arterial infusion of increasing doses of acetylcholine (a vasodilator that stimulates endothelial release of NO), sodium nitroprusside (an exogenous NO donor), and isoproterenol (a beta-adrenergic agonist whose vasodilator effect stems from the combination of direct smooth muscle stimulation and endothelial NO release) were studied in 18 normotensive whites and 18 blacks by use of strain-gauge plethysmography. A blunted vasodilator response to acetylcholine (7.2+/-1.1 versus 14.4+/-1.8 mL. min-1. dL-1; P<0.001) and sodium nitroprusside (8.2+/-1.1 versus 12.1+/-1.3 mL. min-1. dL-1; P<0.001) was observed in blacks compared with whites, suggesting decreased cGMP-mediated smooth muscle relaxation. The vasodilator effect of isoproterenol was lower in blacks than in whites both before (10.9+/-1.7 versus 14.9+/-1.5 mL. min-1. dL-1; P=0.006) and after NG-monomethyl-L-arginine (6.1+/-1.2 versus 10. 1+/-0.8 mL. min-1. dL-1; P<0.001), implying that cAMP-dependent vasodilator response to isoproterenol is diminished in blacks. No significant difference was observed in the hyperemic response to forearm ischemia.Compared with whites, healthy blacks have reduced vasodilation in response to NO-dependent and -independent stimuli. This difference seems to be related to an attenuation in cyclic nucleotide-mediated vascular smooth muscle relaxation and may play a role in the increased prevalence of hypertension and its complications in blacks.
Premedical Students, Admissions Committees, and 'the Physician as an Educated Person'
Authors: Paul S. Rhoads
Journal: JAMA (1982)

SUCCESS in coping with the problems facing modern medicine depends primarily on (1) choosing candidates for medicine with good minds, moral and intellectual integrity, high goals of service, and sustained enthusiasm; and (2) providing them an education in the fundamentals that will, while keeping alive their ultimate goals of service, stimulate their imaginations and provide them with a capacity for growth. <h3>The Applicant Pool</h3> I have had considerable refreshing and enlightening contact with premedical students in a small liberal arts college, Earlham, at Richmond, Ind, which has an excellent record (85.3%) in having its students accepted into medical schools. During the summer months, several students who have just completed their first preclinical year in medical school come to Reid Memorial Hospital, Richmond, for eight weeks of experience in a community hospital. From talking to these students one gains the impression that most of them have a deep desire to serve
Decision tables. Their use for the presentation of clinical algorithms
Authors: R. R. Holland
Journal: JAMA (1975)

A CONSTRUCTIVE approach to the information explosion can be seen in the work of Calvin Kunin, MD, on urinary tract infections (UTIs). The first edition of his book<i>Detection, Prevention, and Management of Urinary Tract Infections</i>is 200 pages long and represents the findings of 240 articles; the second edition, recently published, represents 500 articles and is 300 pages long. Realizing that it would be impossible under the time constraints of practice for everyone to either read or remember accurately the content of his book or the original articles, Dr. Kunin has, in an accompanying article, reduced the content to 0 pages and three flow charts. This was done with the expectation that the information he presents could then be used in the day-to-day practice of medicine for all patients regardless of time constraints, rather than just existing lifelessly between bookcovers. This communication presents decision tables as an alternative to
STUDIES IN METHIONINE METABOLISM. III. THE FATE OF INTRAVENOUSLY ADMINISTERED S35-LABELED-METHIONINE IN NORMAL ADULT MALES, IN PATIENTS WITH CHRONIC HEPATIC DISEASE, “IDIOPATHIC” HYPOPROTEINEMIA AND CUSHING'S SYNDROME 1
Authors: Laurance W. Kinsell, Sheldon Margen, Harold Tarver, Julie McB. Frantz, Erin K. Flanagan, Maxine E. Hutchin, George D. Michaels, David P. McCallie
Journal: Journal of Clinical Investigation (1950)

One microcurie 3.77 X 10' counts per minute under these experimental conditions.All patients were in the fasting state for 12 hours before and five hours after administration of the methionine.Blood specimens were obtained at three-, five-, eight-, 12-, and 24-hour intervals postmethionine during the first day, daily thereafter for the following week in the majority, and at fairly regular intervals thereafter for many weeks.Fractional urine specimens were obtained the first day, then specimens for 24-hour to 72-hour periods thereafter as shown.Stools when obtained were collected in six-day periods for 12 or more days.The blood was fractionated according to the following
THE VISCOSITY OF THE BLOOD OF THE DOG AFTER OBSTRUCTION OF THE UPPER GASTROINTESTINAL TRACT
Authors: Russell L. Haden, Thomas G. Orr
Journal: The Journal of Experimental Medicine (1926)

Estimations of the viscosity of the whole blood and plasma of the dog after experimental upper gastrointestinal tract obstruction are reported. With cardiac obstruction there is a rapid and marked rise in the viscosity of the whole blood and some increase in the viscosity of the plasma. The changes after pyloric obstruction are similar to those observed after cardiac obstruction. After obstruction of the upper jejunum only slight changes are observed. The increase in viscosity parallels quite closely the degree of the toxemia. It is unaccompanied by any marked concentration of the blood.
rAAV2 traffics through both the late and the recycling endosomes in a dose-dependent fashion
Authors: Wei Ding, Liang N. Zhang, Charles Yeaman, John F. Engelhardt
Journal: Molecular Therapy (2006)

Inefficient trafficking of recombinant adeno-associated virus type-2 (rAAV2) to the nucleus is a major barrier for transduction. Using imaging and subcellular fractionation techniques, we evaluated the extent of rAAV2 movement through the late (Rab7) and recycling (Rab11) endosomes. Following rAAV2 infection of HeLa cells, immunoisolation of HA–Rab7- or HA–Rab11-tagged endosomes and intracellular colocalization of Cy3-labeled rAAV2 with EGFP–Rab7 or EGFP–Rab11 markers demonstrated dose-dependent trafficking of rAAV2 through the recycling and late endosomal compartments. At low multiplicities of infection (m.o.i. 100 genomes/cell), rAAV2 predominantly trafficked to the Rab7 compartment. In contrast, rAAV2 predominantly trafficked to the recycling endosome at 100-fold higher m.o.i. siRNA studies inhibiting either Rab7 or Rab11 demonstrated that reducing Rab11 protein levels more significantly inhibited rAAV2 transduction on a per genome basis compared to inhibition of Rab7. Dose–response curves, comparing the m.o.i. of AV2Luc infection to relative transduction, also supported the hypothesis that viral movement through the Rab11 compartment at high m.o.i. is more competent for transgene expression (∼100-fold) than virus that moves through the Rab7 compartment at low m.o.i. These findings suggest that strategies to shunt viral movement from the late to the recycling endosome may be effective at increasing viral transduction for gene therapy.
MESENTERIC EMBOLISM AND THROMBOSIS.A STUDY OF TWO HUNDRED AND FOURTEEN CASES.
Authors: JAMES MARSH JACKSON
Journal: JAMA (1904)

<h3>OPERATION. DR. F. B. HARRINGTON. ⅛ PER CENT. COCAIN.</h3> Six-inch incision along right rectus. Peritoneum dark and free fluid present. Coils of small intestine found flaccid, black and foul smelling. Gangrene found to involve cecum and ascending colon to hepatic flexure, besides all of the ileum. Continuing from gangrenous areas, the intestine changed gradually to almost normal color. At this stage patient became restless and primary ether was given, also for very poor condition, strychnia, 1/20 gr., with no effect. Small perforation found in small intestine, through which much dark venous blood was oozing. Perforation tied with silk. Purse-string stitch of silk put in small intestine and Mixter tube inserted. Small amount of gas escaped, but no intestinal contents. Patient collapsed and died. <h3>AUTOPSY. DR. J. H. WRIGHT.</h3> Sept. 20, 1902. Obturating thrombus of superior mesenteric artery, due to endarteritis. Hemorrhagic infarct of small intestine, and of portion
DNA content and Ks8.12 binding of the psoriatic lesion during treatment with the vitamin D3 nalogue MC903 and betamethasone
Authors: S.DE MARE, E.G.J.M.DE JONG, P.C.M. KERKHOF
Journal: British Journal of Dermatology (1990)

Journal Article DNA content and Ks8.12 binding of the psoriatic lesion during treatment with the vitamin D3 nalogue MC903 and betamethasone Get access S.DE MARE, S.DE MARE Department of Dermatology, University Hospital of Nijmegen, Javastraat 104, 6524 MJ Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar E.G.J.M.DE JONG, E.G.J.M.DE JONG Department of Dermatology, University Hospital of Nijmegen, Javastraat 104, 6524 MJ Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar P.C.M. VAN DE KERKHOF P.C.M. VAN DE KERKHOF Department of Dermatology, University Hospital of Nijmegen, Javastraat 104, 6524 MJ Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 123, Issue 3, 1 September 1990, Pages 291–295, https://doi.org/10.1111/j.1365-2133.1990.tb06287.x Published: 01 September 1990
ALK as a novel lymphoma-associated tumor antigen: identification of 2 HLA-A2.1–restricted CD8+ T-cell epitopes
Authors: Lorena Passoni, Antonio Scardino, Carla Bertazzoli, Barbara Gallo, Addolorata M. L. Coluccia, François A. Lemonnier, Konstadinos Kosmatopoulos, Carlo Gambacorti-Passerini
Journal: Blood (2002)
Plans for future influenza pandemics must raise awareness of Reye's syndrome
Authors: S. Hall, R. Lynn
Journal: BMJ (1998)

EDITOR—Walker and Christie report that the index patient in the outbreak of avian influenza in Hong Kong died of Reye's syndrome.1 Reye's syndrome was an important cause of death and severe neurological morbidity in the United States in the 1970s and early 1980s, particularly during influenza epidemics. Its incidence fell sharply after recognition of its association with aspirin and the introduction of public education and warning labelling on aspirin products.2 …
Incidence of diabetic retinopathy in people with type 2 diabetes mellitus attending the Diabetic Retinopathy Screening Service for Wales: retrospective analysis
Authors: R. L. Thomas, F. Dunstan, S. D. Luzio, S. Roy Chowdury, S. L. Hale, R. V. North, R. L. Gibbins, D. R. Owens
Journal: BMJ (2012)

<h3>Abstract</h3> Nuclear clearance of the DNA/RNA-binding protein TDP-43 is a pathologic hallmark of amyotrophic lateral sclerosis and frontotemporal dementia that remains unexplained. Moreover, our current understanding of TDP-43 nucleocytoplasmic shuttling does not fully explain the predominantly nuclear localization of TDP-43 in healthy cells. Here, we used permeabilized and live-cell models to investigate TDP-43 nuclear export and the role of RNA in TDP-43 localization. We show that TDP-43 nuclear efflux occurs in low-ATP conditions and independent of active mRNA export, consistent with export by passive diffusion through nuclear pore channels. TDP-43 nuclear residence requires binding to GU-rich nuclear intronic pre-mRNAs, based on the induction of TDP-43 nuclear efflux by RNase and GU-rich oligomers and TDP-43 nuclear retention conferred by pre-mRNA splicing inhibitors. Mutation of TDP-43 RNA recognition motifs disrupts TDP-43 nuclear accumulation and abolishes transcriptional blockade-induced TDP-43 nuclear efflux, demonstrating strict dependence of TDP-43 nuclear localization on RNA binding. Thus, the nuclear abundance of GU-rich intronic pre-mRNAs, as dictated by the balance of transcription and pre-mRNA processing, regulates TDP-43 nuclear sequestration and availability for passive nuclear export.
ABC of clinical genetics. Detection of carriers.
Authors: H. M. Kingston
Journal: BMJ (1989)

Identifying carriers of genetic disorders in families or populations at risk plays an important part in preventing genetic disease.A carrier is a healthy Obligate carriers* person who possesses the mutant gene for an inherited disorder in the E-r-Q heterozygous state.The term carrier is therefore restricted to people at risk Autosomal dominant L of transmitting mendelian disorders and does not apply to parents whose Pcrson with affected 1 children have chromosomal abnormalities or congenital malformations parenit and child such as neural tube defect.An exception is that people who have balanced chromosomal translocations are referred to as carriers as the inheritance of balanced or unbalanced translocations follows mendelian * * principles.Autosomal recessive ID-Neurofibromatoss .disease).Although testing for carrier state can have important benefits in conditions in which the prognosis is improved by early detection, Tuberous sclerosispresymptomatic diagnosis of severe disorders, such as Huntington's von Hippel-Lindau disease chorea, that are not amenable to treatment presents problems.Exclusion of carrier state is, however, equally important, removing anxiety about transmitting the condition to offspring and the need for long term follow up.
Depressed Heart Rate Variability and Arterial Baroreflex in Conscious Transgenic Mice With Overexpression of Cardiac G <sub>sα</sub>
Authors: Masami Uechi, Kuniya Asai, Motohisa Osaka, Amelia Smith, Naoki Sato, Thomas E. Wagner, Yoshihiro Ishikawa, Hirokazu Hayakawa, Dorothy E. Vatner, Richard P. Shannon, Charles J. Homcy, Stephen F. Vatner
Journal: Circulation Research (1998)

Abstract —Recently, we developed a transgenic mouse with cardiac-specific G sα overexpression (TG mouse), which exhibits enhanced postsynaptic β-adrenergic receptor signaling, ultimately developing a cardiomyopathy. The goal of the present study was to determine whether cardiac G sα overexpression alters autonomic cardiovascular control, which could shed light on the mechanism responsible for the later development of cardiomyopathy. Mean arterial pressure was increased ( P &lt;.05) in conscious, chronically instrumented TG mice (123±1 mm Hg) compared with age-matched wild-type (WT) control mice (103±1 mm Hg). Respiratory frequency was increased ( P &lt;.05) in TG mice (269±26/min) compared with WT mice (210±20/min). By use of telemetric techniques, baseline heart rate (HR) was elevated ( P &lt;.05) in conscious, untethered TG mice (696±13 bpm) compared with WT mice (568±28 bpm). Intrinsic HR, after propranolol and atropine or after ganglionic blockade with hexamethonium, was not different between TG and WT mice. Both the normal minute-to-minute and circadian variations of HR observed in WT mice were markedly blunted in TG mice. HR variability was assessed by the time-domain and frequency-domain methods. At baseline, time-domain analysis indices were reduced ( P &lt;.05) in TG mice compared with WT mice. Although the low frequency (LF) component was higher ( P &lt;.05) than the high frequency (HF) component in WT mice, the LF component was less ( P &lt;.05) than the HF component in TG mice. In addition, arterial baroreflex regulation of HR was markedly blunted in TG mice in response to both nitroglycerin-induced hypotension and phenylephrine-induced hypertension. The reduced LF/HF ratio in TG mice was surprising in view of enhanced β-adrenergic signaling and may be due to reduced neural tone secondary to the elevated arterial pressure or alterations in arterial baroreflex control. Dobutamine infusion in WT mice also resulted in depressed HR variability. The combination of elevated baseline HR, arterial pressure, and respiratory frequency suggests that enhanced β-adrenergic signaling in TG mice results in reduced HR variability, in terms of both minute-to-minute variability and the lack of circadian variations in HR. The lack of normal HR variability in general and the failure of HR to decline, even during sleep, may actually be critical mechanisms contributing to the ultimate development of cardiomyopathy in these animals.
The Small Corks Test
Authors: Louis R. Caplan
Journal: JAMA (1981)

A CAREFUL, thorough neurologic examination takes time. Detailed assessment of limb sensation can be an especially tedious and time-consuming part of the examination; for this reason, sensory testing is all too frequently omitted. A rapid screening procedure capable of detecting significant somatosensory deficits would be enthusiastically welcomed by most busy clinicians. Such a test should (1) be simply and quickly performed; (2) have materials that are easy to obtain, carry, and replace; and (3) rarely miss dysfunction (false-negative findings). False-positive results are less important, since the abnormal screening test would merely indicate the need for more careful testing. I describe the "small corks test"—a procedure that fulfills the requirements cited. <h3>Methods</h3> Four small corks purchasable in most hardware or five and dime stores were used. The smallest cork measures 1 cm in largest diameter and 1 cm in height. The largest cork is 2 cm in height and largest diameter;
Association Between Extracellular Matrix Expansion Quantified by Cardiovascular Magnetic Resonance and Short-Term Mortality
Authors: Timothy C. Wong, Kayla Piehler, Christopher G. Meier, Stephen M. Testa, Amanda M. Klock, Ali A. Aneizi, Jonathan Shakesprere, Peter Kellman, Sanjeev G. Shroff, David S. Schwartzman, Suresh R. Mulukutla, Marc A. Simon, Erik B. Schelbert
Journal: Circulation (2012)

Background— Extracellular matrix expansion may be a fundamental feature of adverse myocardial remodeling, it appears to be treatable, and its measurement may improve risk stratification. Yet, the relationship between mortality and extracellular matrix is not clear because of difficulties with its measurement. To assess its relationship with outcomes, we used novel, validated cardiovascular magnetic resonance techniques to quantify the full spectrum of extracellular matrix expansion not readily detectable by conventional cardiovascular magnetic resonance. Methods and Results— We recruited 793 consecutive patients at the time of cardiovascular magnetic resonance without amyloidosis or hypertrophic cardiomyopathy as well as 9 healthy volunteers (ages 20–50 years). We measured the extracellular volume fraction (ECV) to quantify the extracellular matrix expansion in myocardium without myocardial infarction. ECV uses gadolinium contrast as an extracellular space marker based on T1 measures of blood and myocardium pre— and post–gadolinium contrast and hematocrit measurement. In volunteers, ECV ranged from 21.7% to 26.2%, but in patients it ranged from 21.0% to 45.8%, indicating considerable burden. There were 39 deaths over a median follow-up of 0.8 years (interquartile range 0.5–1.2 years), and 43 individuals who experienced the composite end point of death/cardiac transplant/left ventricular assist device implantation. In Cox regression models, ECV related to all-cause mortality and the composite end point (hazard ratio, 1.55; 95% confidence interval, 1.27–1.88 and hazard ratio, 1.48; 95% confidence interval, 1.23–1.78, respectively, for every 3% increase in ECV), adjusting for age, left ventricular ejection fraction, and myocardial infarction size. Conclusions— ECV measures of extracellular matrix expansion may predict mortality as well as other composite end points (death/cardiac transplant/left ventricular assist device implantation).
Abstract 4901: Clostridium cluster XIVa species an early biomarker in radiation injury
Authors: Ishfaq Ahmed, William McLauglin, Shrikant Anant, Shahid Umar, Rao V. Papineni
Journal: Cancer Research (2014)

Abstract Radiation therapy is being used in the treatment of nearly 60% of the current cancer patients. In spite of the best efforts to provide special care in minimizing radiation exposure, significant radiation injury remains a common side-effect particularly to the gastro intestinal tract. Severe injury to GI tract may lead to multiple organ dysfunction syndrome. The status of fecal microbiota has been proposed as a rapid diagnostic platform in radiation injury. Gut microbes play a role in immunity, health, and disease. Imbalances in gut microbiota are related to numerous disorders, such as inflammatory bowel disease, colorectal cancer (CRC), and atopy. In patients with immune suppression due to high-dose chemotherapy or that undergoing radiation therapy, disruption of the microbiota through antibiotics and impairment of host immunity gives rise to perturbations favoring intestinal domination by pathogenic species, resulting in increased bacterial translocation and susceptibility to systemic infection. Here, using real-time PCR assays, we assessed the immediate changes and quantitative alterations to fecal microbiota in response to radiation injury. Swiss-albino Mice were subjected to 10 Gy X-ray whole body irradiation doses using commercially available X-RAD 320 irradiator (1Gy/min; F2 beam hardening filter 1.5mm Al, 0.25mm Cu, 0.75mm Sn; Precision X-ray inc, USA). Fecal samples collected immediately after the radiation exposure were analyzed. We show that Clostridium cluster XIVa that accounts for almost 60% of the mucin-adhered microbiota is significantly increased (11.71 +/- 0.29 fold n=6) in the fecal samples, compared to the total bacteria and other bacteria that tend to enrich in the luminal region. Along with the Bacteroidetes and Proteobacteria from the luminal region, minimal changes in the levels of Firmicutes that colonize the mucin layer were observed. Further, these changes varied considerably between the subjects and were inconsistent compared to the Clostridium cluster species. Clostridium cluster XIVa has been proposed to be the mucosal butyrate producers producing butyrate close to the epithelium. This enhances butyrate bioavailability required in treating diseases such as inflammatory bowel disease. These findings provide opportunities to evaluate the potential use of intestinal microbiota as biomarkers in radiation injury. Also, provides insights into the microbial changes tantamount to the radiation induced GI injury. Citation Format: Ishfaq Ahmed, William McLauglin, Shrikant Anant, Shahid Umar, Rao V. Papineni. Clostridium cluster XIVa species an early biomarker in radiation injury. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4901. doi:10.1158/1538-7445.AM2014-4901