tbuckley/cabot-search huggingface dataset:
Genetic isolation of a region of chromosome 8 that exerts major effects on blood pressure and cardiac mass in the spontaneously hypertensive rat.
Authors: V Kren, M Pravenec, S Lu, D Krenova, J M Wang, N Wang, T Merriouns, A Wong, E St Lezin, D Lau, C Szpirer, J Szpirer, T W Kurtz
Journal: Journal of Clinical Investigation (1997)

The spontaneously hypertensive rat (SHR) is the most widely studied animal model of essential hypertension. Despite > 30 yr of research, the primary genetic lesions responsible for hypertension in the SHR remain undefined. In this report, we describe the construction and hemodynamic characterization of a congenic strain of SHR (SHR-Lx) that carries a defined segment of chromosome 8 from a normotensive strain of Brown-Norway rats (BN-Lx strain). Transfer of this segment of chromosome 8 from the BN-Lx strain onto the SHR background resulted in substantial reductions in systolic and diastolic blood pressure and cardiac mass. Linkage and comparative mapping studies indicate that the transferred chromosome segment contains a number of candidate genes for hypertension, including genes encoding a brain dopamine receptor and a renal epithelial potassium channel. These findings demonstrate that BP regulatory gene(s) exist within the differential chromosome segment trapped in the SHR-Lx congenic strain and that this region of chromosome 8 plays a major role in the hypertension of SHR vs. BN-Lx rats.
Systemic Tolerability of Intermittent Topical Corticosteroid Therapy Using Salivary Cortisol Measurements in Infants with Atopic Dermatitis
Authors: T. Fukuie, S. Sano, I. Nomura, M. Narita, T. Taguchi, T. Ogata, K. Matsumoto, Y. Ohya
Journal: Journal of Allergy and Clinical Immunology (2012)
Family planning clinics: Most give a good service
Authors: J. Guillebaud, D. J Moran
Journal: BMJ (1993)

issues which may emerge when a statutory service and a voluntary organisation work together.These issues were debated and a set of guidelines were established for all staff involved in the project.The service provision for adolescents with substance misuse problems could progress by the establishment of formal links between the adult substance misuse and child adolescent psychiatry services, the development of training programmes for staff interested in working in this area, a willingness to work alongside voluntary agencies, and clarification of the issues relating to assessment and treatment ofyoung people under 16.
Abstract C27: Potential contributions of genome-stabilizing activity of NM23 to its metastasis suppressor function in melanoma
Authors: Stuart G. Jarrett, Marian Novak, Gemma S. Cook, David M. Kaetzel
Journal: Cancer Research (2013)

Abstract Metastasis suppressor activity of NM23-M1 (NM23-H1 in human) in melanoma has been established using melanoma cell lines in culture and, more recently, in a model of UV-induced melanoma using NM23 knockout mice. While NM23-M1/H1 is clearly a suppressor of melanoma cell motility, we have recently shown it also exhibits genome-stabilizing activity, promoting repair of both spontaneous and UV-induced DNA damage via the nucleotide excision repair pathway. These findings suggest NM23 proteins may also inhibit metastasis by suppressing acquisition of metastasis-driving mutations and other genomic aberrations. To dissect the molecular mechanisms through which NM23 contributes to genomic stability, this study focused on the double-strand break repair (DSBR) pathway. All members of the NM23 family of proteins possess nucleoside diphosphate kinase (NDPK) activity, which could enhance nucleotide availability during polymerase-mediated repair, and 3'5' exonuclease activity which has been suggested to be critical in the non-homologous end-joining (NHEJ) pathway of DSBR. To first determine whether NM23 is indeed recruited to DSBs, these lesions were produced in the human melanoma cell line WM793 using a tamoxifen-inducible form of the restriction endonuclease I-PpoI via a retroviral vector. Induction of I-PpoI-catalyzed DSBs resulted in recruitment of both endogenous NM23 and recombinant Flag-tagged H1 (Flag-H1) to a known I-PpoI cleavage site within 30 min, as demonstrated by chromatin immunoprecipitation. The rapid appearance of NM23-H1 at the DSB coincided with that of the damage sensor ATM, and disappearance of histone 2B. Forced expression of NM23-H1 resulted in significantly enhanced repair of the known I-PpoI-induced DSB site, shown using a quantitative PCR across the lesion, indicating a functional contribution of the protein to DSBR. Induction of DSBs resulted in colocalization of Flag-H1 with γ-histone 2AX within small intranuclear foci, also consistent with recruitment of NM23-H1 directly to DSB lesions. Induction of DSBs using the DNA topoisomerase II inhibitor etoposide resulted in rapid nuclear colocalization within 5 minutes of Flag-H1 and ribonucleotide reductase, suggesting cooperative actions of these two enzymatic activities during DSBR. These studies are the first to demonstrate recruitment of NM23-H1 directly to sites of DNA damage, and suggest the possibility that NM23 deficiency in melanoma and other human cancers accelerates the acquisition of metastasis-driving mutations during cancer progression. Citation Format: Stuart G. Jarrett, Marian Novak, Gemma S. Cook, David M. Kaetzel. Potential contributions of genome-stabilizing activity of NM23 to its metastasis suppressor function in melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C27.
Waning Efficacy of Experimental Malaria Vaccine
Authors: M. J. Friedrich
Journal: JAMA (2013)

The efficacy of the malaria vaccine candidate RTS,S/AS01E against episodes of malaria diminishes over time and also varies with exposure to the Plasmodium falciparum parasite, according to data from a long-term follow-up of a phase 2 trial of the vaccine in Africa (Olotu A et al. N Engl J Med. 2013;368[12]:1111-1120).

After 4 years of follow-up of 320 of 447 children in Kenya who had been vaccinated at 5 to 17 months of age, protection declined each year to almost 0 by year 4. The vaccine efficacy varied with exposure to malaria. In areas of high malaria transmission, protection faded even faster than it did in areas with lower transmission. The authors suggest that children in the areas of higher transmission who were vaccinated may have had less exposure to blood-stage parasites and therefore developed natural immunity more slowly than the control group.
Cholera epidemic in Haiti is blamed on poor sanitation
Authors: J. Zarocostas
Journal: BMJ (2011)

Rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome (ODS), a severe demyelination disease. The microglia that accumulate in the demyelinative lesions may play a detrimental role in the pathogenesis of ODS by producing proinflammatory cytokines, suggesting that they may be a target for therapeutic intervention. Here, we investigated whether minocycline, a selective and potent inhibitor of microglial activation, could protect against ODS in rats. We induced hyponatremia by liquid diet feeding and dDAVP infusion. Rapid correction of the hyponatremia 7 days later resulted in neurologic impairment with severe demyelinative lesions. Activated microglia accumulated at the site of demyelination. Treatment with minocycline within 24 hours of rapid correction, however, was protective: rats exhibited minimal neurologic impairment, and survival improved. Histologic analysis showed that minocycline inhibited demyelination and suppressed the accumulation of microglia at the site of demyelination. Real-time RT-PCR and immunohistochemical analyses showed that minocycline inhibited the activity of microglia and the expression of inflammatory cytokines (<i>e.g.</i> IL-1β, inducible nitric-oxide synthase, and TNF-α), monocyte chemoattractant protein-1, and matrix metalloproteinase-12 in microglia. These results demonstrate that minocycline can protect against ODS by inhibiting the activation and accumulation of microglia at the site of demyelinative lesions, suggesting its possible use in clinical practice.
THE INHIBITORY EFFECT OF POLYSACCHARIDE ON MUMPS VIRUS MULTIPLICATION
Authors: Harold S. Ginsberg, Walther F. Goebel, Frank L. Horsfall
Journal: The Journal of Experimental Medicine (1948)

Polysaccharides derived from type-specific Friedländer bacilli cause inhibition of the multiplication of mumps virus in the allantoic sac of the chick embryo. As little as 5 microg. of polysaccharide is effective as an inhibitor. Inhibition of multiplication is obtained when polysaccharide is injected as long as 4 days after inoculation of virus. Chemical studies have shown that the structural configurations of the polysaccharide responsible for specific serological activity are not identical with those which determine the inhibitory effect relative to mumps virus. The possible mechanisms of the inhibition of viral multiplication by means of polysaccharides are discussed.
Destruction of case records.
Authors: E C Jewesbury
Journal: BMJ (1971)

largeness in body, nor no sickness, nor lack of natural functions in those things that properly belong to the procreation of child- ren, but contrarywise, by judgement of physicians that know her estate on those things and by the opinion of women, being most acquainted with her Majesty's body in such things as properly appertain, to show probability of her aptness to have children, even at this day."3If the evidence of this memorandum is accepted, the factors which influenced Elizabeth against marriage were probably political, psychological, and religious, not to mention personal survival, rather than any physical complaint.
Pulmonary Release and Coronary and Peripheral Consumption of Big Endothelin and Endothelin-1 in Severe Heart Failure
Authors: Karl Stangl, Thomas Dschietzig, Christoph Richter, Michael Laule, Verena Stangl, Elsa Tanis, Gert Baumann, Stephan B. Felix
Journal: Circulation (2000)

We investigated plasma endothelin (ET) levels in patients with congestive heart failure (CHF) during treatment for acute decompensation; we also measured imbalances in ET peptides across the pulmonary, coronary, and peripheral circulation. Methods and Results-In patients with severe CHF (n=21; cardiac index [CI], 1.9+/-0.2 L. min(-1). m(-2); pulmonary capillary wedge pressure [PCWP], 31+/-1 mm Hg), vasodilation was achieved with the nitric oxide donor sodium nitroprusside (n=11) or with the alpha(1)-antagonist urapidil (nitric oxide-independent, n=10). ET concentrations were determined from arterial blood and blood from the pulmonary artery, coronary sinus, and antecubital vein. Depending on sites of measurement, baseline big ET and ET-1 levels were, respectively, 12 to 16 times and 5 to 11 times higher than in controls (n=11), and 4 to 6 times and 2 to 3 times higher than in patients with moderate CHF (n=10; CI, 2.7+/-0.3 L. min(-1). m(-2); PCWP, 14+/-2 mm Hg). Patients with severe CHF demonstrated pulmonary net release and coronary and peripheral net consumption of both peptides (ie, arterial levels [big ET, 7.3+/-1.3 pmol/L; ET-1, 1.8+/-0.1 pmol/L] were higher than levels in the pulmonary artery [6.7+/-1.2 pmol/L; 1. 3+/-0.1 pmol/L], coronary sinus [6.4+/-1.0 pmol/L; 1.4+/-0.1 pmol/L], and antecubital vein [6.6+/-1.1 pmol/L; 1.3+/-0.1 pmol/L]). In these patients, sodium nitroprusside (SNP) and urapidil resulted in comparable hemodynamic improvement after 6 hours (CI: SNP, 63+/-2%; urapidil, 72+/-3%; PCWP: SNP, -50+/-2%; urapidil, -47+/-2%) and a maximum decrease in ET peptides by >50%. After 3 hours, pulmonary net release and coronary and peripheral net consumption were no longer detectable.In patients with severe CHF, the lungs act as a producer and the heart and the periphery act as consumers of elevated circulating ETs. Short-term vasodilator therapy decreases ETs and restores their pulmonary, coronary, and peripheral balance.
Anatomy: A Regional Study of Human Structure
Authors: John L. Terry
Journal: JAMA (1960)

It is a pleasure to note the appearance of a textbook of anatomy written in readily understandable language which has made a real contribution toward the correlation of the basic sciences of physiology, pharmacology, and embryology along with the study of growth anatomy. The authors have succeeded in presenting a text that is unusually concise and succinct. These features are wonderfully complemented by the great numbers of well-prepared illustrations, plates, and tables, most of which are new and not merely reproductions of previously utilized figures. This enlightening text has apparently bypassed a great deal of the minutia that so frequently burdened the text of previous anatomic works and has substituted a great wealth of correlative material in the form of many significant radiographs as well as a host of well-prepared diagrammatic sketches. There is relatively little new in anatomy, and all that can be expected of a textbook of this
Perceptual experience as a bridge between the retina and a bicoded cognitive map
Authors: Frank H. Durgin, Zhi Li
Journal: Behavioral and Brain Sciences (2013)

Abstract The bicoded cognitive maps described by Jeffery et al. are compared to metric perceptual representations. Systematic biases in perceptual experience of egocentric distance, height, and surface orientation may reflect information processing choices to retain information critical for immediate action (Durgin et al. 2010a). Different information processing goals (route planning vs. immediate action) require different metric information.
Volunteer scheme for dysphasia and allied problems in stroke patients.
Authors: V E Griffith
Journal: BMJ (1975)

With nearly 100 000 heavily handicapped hemiplegics in Great Britain' stroke is a major medical problem.Though most stroke patients benefit from their period of rehabilitation there inevitably comes a time when, with many problems remaining, they are discharged home to their families.The despair felt by the patient and his relatives may be overwhelming, and in most cases little support is available.The problem is particularly acute when speech is affected since there is a national shortage in some areas a total absence-of speech therapists.One source of help which has not been fully explored is the use of volunteer helpers working within a responsible organization and co- operating with doctors, speech therapists, and other professional workers.Such a project has been sponsored by the Chest and Heart Association and financed by the Clarkson Foundation.This report describes the pilot scheme and records some observations made after 16 months' work in two areas, the Chilterns and Oxford city.
REQUIREMENTS FOR ADMISSION TO MEDICAL SCHOOLS.
Authors: JAMES RUSSELL PARSONS
Journal: JAMA (1903)

It will aid us in discussing this topic to review briefly the quantitative requirements now exacted : 1. In accordance with statutory provision. 2. By individual medical schools. In the state of New York a preliminary general education equivalent to graduation from a four-year high-school course after a completed eight-year elementary course is prescribed by statute as the minimum standard for license to practice medicine. Quantitatively this standard approximates that demanded in Continental Europe. Qualitatively it leaves much to be desired. The defects are being remedied, as I shall show later. New Hampshire, Ohio and Vermont have similar requirements, but they are not as rigidly enforced. Wisconsin demands the equivalent of admission to the junior year of an accredited high school. Delaware, Maryland, New Jersey and Pennsylvania prescribe a "common school education," Louisiana "a fair primary education," Illinois and Iowa less than one year of high-school work Maine and Virginia
Quantitative assessment of myocardial ischemia and necrosis by continuous vectorcardiography and measurement of creatine kinase release in patients.
Authors: M Sederholm, P Grøttum, L Erhardt, J Kjekshus
Journal: Circulation (1983)

The accuracy of the use of the maximal QRS vector difference to estimate myocardial infarct size irrespective of infarct location was compared with that of measurement of cumulative creatine kinase (CK) release. Sixty patients with acute myocardial infarction and a history of symptoms of less than 4 hr duration were followed for 24 to 72 hr with orthogonal vectorcardiography and CK release analysis. Spatial QRS vector differences were calculated between the first QRS complex recorded and subsequent QRS complexes at timed intervals. The QRS vector difference increased rapidly and reached a plateau at an average 12.1 hr after onset of symptoms, as compared with 34.0 hr for the cumulated CK release. In 42% of the patients a stepwise progression of infarct evolution was observed. Irrespective of infarct location the maximal spatial ST vector magnitude was related to the ultimate QRS vector difference (r = .80) and to the cumulative amount of CK released (r = .64). Furthermore, maximal QRS vector difference correlated well with the maximal cumulative CK release (r = .64) Ten patients had possible infarct expansion, as indicated by recurrent QRS changes without concomitant CK release. Fifteen patients had infarct extension that was indicated by secondary CK release and that in seven patients was associated with further QRS changes. Infarct extension caused an approximate 25% increase in infarct size. Spatial ST vector magnitude, QRS vector difference, and cumulative CK release are complementary measures in the quantification of evolving myocardial injury after acute coronary occlusion and in the determination of sequels to therapeutic interventions.
Vertebral deformities as predictors of non-vertebral fractures
Authors: H Burger, P L A Van Daele, D Algra, A Hofman, D E Grobbee, H E Schutte, J C Birkenhager, H A Pols
Journal: BMJ (1994)

Aryl hydrocarbon receptor (AhR)-dependent enzymes are involved in the biotransformation of harmful xenobiotics into more easily excretable metabolites. Cross-talk between the AhR pathway and the hypoxia inducible factor-1α (HIF-1α) pathway has been demonstrated previously, although the mechanism remains unclear and quite controversial. Because nickel is known to mimic hypoxia, we investigated the effects of short-term nickel exposure on AhR-dependent gene expression. Gene-chip analysis identified several AhR-dependent genes that are suppressed by exposure to nickel. Using Northern blots, we then confirmed that nickel can down-regulate both the basal and benzo[<i>a</i>]pyrene-inducible expression of AhR-dependent genes in mouse and human cell lines. Using a HIF-1α knockout cell line and 3-[2-[4-(bis-(4-fluorophenyl) methylene]-1-piperidinyl)ethyl]-2,3-dihydro-2-thioxo-4(1H)quinazolinone (R59949), which blocks HIF-1α protein accumulation, we show HIF-1α-independent suppression of AhR-dependent genes by nickel. Desferrioxamine and hypoxia were also able to suppress the basal and inducible expression levels of AhR-regulated genes. Finally, dimethyloxalylglycine, an inhibitor of Fe(II)- and 2-oxoglutarate-dependent dioxygenases also inhibited AhR-dependent expression in a HIF-1α-independent manner. Our data suggest that an Fe(II)-, oxoglutarate-, and oxygen-dependent enzyme may directly or indirectly be involved in the regulation of AhR-dependent transcriptional activity by nickel and other hypoxia-mimicking agents.
False Positive Diagnosis of Metastatic Esophageal Carcinoma on Positron Emission Tomography
Authors: Neil Hansen, Richard K. J. Brown, Asra Khan, Kirk A. Frey, Mark Orringer
Journal: Clinical Nuclear Medicine (2010)

Esophageal cancer has been increasing in incidence for the last several decades. The current staging evaluation includes computed tomography, endoscopic ultrasonography, and F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), which influences the treatment options. PET/CT is limited in its ability to differentiate hypermetabolic metastatic disease from acute/chronic inflammatory conditions, and this must be considered during interpretation. This is the case report of a 77-year-old man with esophageal cancer whose PET/CT demonstrated increased F-18 FDG uptake in the right lobe of the liver. This was originally interpreted at an outside institution as suspicious for metastatic disease, which would have precluded potential surgical cure. Subsequent reinterpretation and additional imaging including magnetic resonance imaging suggested that the uptake in the liver was likely due to adjacent gallbladder inflammation. On the basis of this interpretation, an abdominal exploration, liver biopsy, cholecystectomy, and transhiatal esophagectomy were performed. Final pathology of the gallbladder revealed perforated cholecystitis and a pericholecystic abscess (related to a prior septic episode), which were responsible for the increased radiotracer uptake. This case is presented to illustrate the importance of considering benign etiologies that may mimic metastatic disease when interpreting PET/CT scans.
Early platelet consumption in pre-eclampsia.
Authors: C W Redman, J Bonnar, L Beilin
Journal: BMJ (1978)

One hundred and thirty-one women with chronic hypertension were studied serially during pregnancy to determine the sequence of events in the development of superimposed pre-eclampsia and to discover the time of onset. Twenty-seven women developed a sustained rise in plasma urate concentrations, which began at about 28 weeks' gestation and which is characteristic of pre-eclampsia. The mean platelet count was already significantly reduced and continued to fall until delivery, which was on average at 36 weeks' gestation. A comparable but smaller decrease in platelet count was seen in 55 women who had borderline but consistent increases in plasma urate concentrations. In 49 women whose plasma urate concentrations remained steady the platelet count did not change significantly before delivery. The reduced platelet count in women who develop pre-eclampsia suggests that increased platelet consumption is an early feature of the disorder.
Insulin-Dependent Diabetes Mellitus: The Initial Lesion
Authors: George F. Cahill, Hugh O. McDevitt
Journal: New England Journal of Medicine (1981)

SUFFICIENT evidence has accumulated over the past decade to allow the statement that insulin-requiring, or insulin-dependent, diabetes mellitus (IDDM; also known as juvenile-onset, Type I, ketosis-prone, or labile diabetes) is pathogenically a distinct disorder from non-insulin-dependent diabetes (NIDDM; also known as maturity-onset, Type II, non-ketosis-prone, or stable diabetes).1 , 2 This separation into two broad categories is made on the basis of several factors, such as the mean age at onset, the association with certain alleles in the major histocompatibility complex (HLA associations), the presence of circulating islet-cell antibodies, the round-cell infiltration in the endocrine pancreas, and other phenomena that are all . . .
PRESCRIBING OF LENSES FOR CLOSE WORK
Authors: MARK D. STEVENSON
Journal: JAMA (1910)

It will be possible to discuss only certain phases of this broad subject. Some procedures do not seem to be sufficiently well known, and require elucidation and emphasis in order to secure their more general adoption by those who prescribe lenses for the eyes. Before considering the prescribing of lenses for close work, the muscle conditions and static refraction for distance should be correctly determined. The latter is usually impossible without the proper use of cycloplegics, except in certain cases of myopia and in some people past middle life whose accommodation is weak or easily controlled. Sometimes the examiner must be satisfied with partial corrections, because fatigued yet determined, hypertrophied, habit-controlled, spasmodically contracting muscles are by no means limited to the young, but are often found in the eyes of the middle-aged with their more inelastic resisting lenses.  There are many young persons who suffer more or less distress, e.