tbuckley/cabot-search huggingface dataset:
Clinical correlation of miR-375 and alpha-fetoprotein in hepatocellular carcinoma: Comparison in mice and humans
Authors: Cheng-Maw Ho, Po-Huang Lee, Rey-Heng Hu
Journal: Hepatology (2011)

We read with great interest the article by Kowalik et al.,1 recently published in Hepatology. The authors found that hepatocellular carcinomas (HCCs) developed in mice that were administered diethylnitrosamine and then repeatedly treated with the mitogen 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene. These mice showed increased expression levels of the transcriptional coactivator Yes-associated protein (YAP), and these increased expression levels were associated with the down-regulation of miR-375 expression, which is known to control YAP expression,2 and with enhanced levels of alpha-fetoprotein (AFP), which is encoded by the target gene of YAP. However, the inverse association between miR-375 and AFP expression was not dose-dependent. We describe our single-center experience with 157 HCC patients who underwent primary resection. The patients were divided into two groups on the basis of the mean levels of miR-375 expression in all tumor tissues, which were determined using an miRNA array and validated by real-time polymerase chain reaction (PCR) analysis. Ten samples from living donor livers (mean [SD] miRNA expression, 13.85 [0.57]) were used as controls. miR-375 expression was down-regulated in HCCs. The clinicopathologic characteristics of the patients are summarized in Table 1. We found that preoperative serum AFP levels in the group showing less reduction in miR-375 expression were significantly higher than those in the group showing higher levels of reduction in miR-375 expression. The findings for the other factors were comparable in both groups. In summary, our results suggest that AFP expression in HCCs was not solely regulated by the axis of miR-375-YAP-AFP. Cheng-Maw Ho M.D.*, Po-Huang Lee M.D., Ph.D.*, Rey-Heng Hu M.D., Ph.D.*, * Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
A rare type of atrial septal defect
Authors: R. J. M. McCormack, D. Pickering, I. I. Smith
Journal: Thorax (1968)

A previously unrecorded cardiac anomaly is described. A defect existed in the lowest part of the atrial septum straddling the orifice of the inferior vena cava so that this vessel opened into both atria. There was an associated anomalous connexion of the right pulmonary veins to the right atrium. The septal defect was recognized only at necropsy. As in the case of a sinus venosus atrial defect, it is suggested that the fundamental embryological error responsible for the production of the rare defect here described is laevo-position of the sino-atrial orifice.
Broad Therapeutic Benefit After RNAi Expression Vector Delivery to Deep Cerebellar Nuclei: Implications for Spinocerebellar Ataxia Type 1 Therapy
Authors: Megan S Keiser, Ryan L Boudreau, Beverly L Davidson
Journal: Molecular Therapy (2014)

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant, late-onset neurodegenerative disease caused by a polyglutamine (polyQ) expansion in the ataxin-1 protein, which causes progressive neurodegeneration in cerebellar Purkinje cells and brainstem nuclei. Here, we tested if reducing mutant ataxin-1 expression would significantly improve phenotypes in a knock-in (KI) mouse model that recapitulates spatial and temporal aspects of SCA1. Adeno-associated viruses (AAVs), expressing inhibitory RNAs targeting ataxin-1, were injected into the deep cerebellar nuclei (DCN) of KI mice. This approach induced ataxin-1 suppression in the cerebellar cortex and in brainstem neurons. RNA interference (RNAi) of ataxin-1 preserved cerebellar lobule integrity and prevented disease-related transcriptional changes for over a year. Notably, RNAi therapy also preserved rotarod performance and neurohistology. These data suggest that delivery of AAVs encoding RNAi sequences against ataxin-1, to DCN alone, may be sufficient for SCA1 therapy.
Relationships of Plasma Interleukin-18 Concentrations to Hyperhomocysteinemia and Carotid Intimal-Media Wall Thickness in Patients With Type 2 Diabetes
Authors: Yoshimasa Aso, Ki-ichi Okumura, Kohzo Takebayashi, Sadao Wakabayashi, Toshihiko Inukai
Journal: Diabetes Care (2003)

OBJECTIVE—We compared plasma interleukin (IL)-18 concentrations in patients with type 2 diabetes with those in age-matched control subjects and investigated whether plasma IL-18 was associated with plasma total homocysteine (tHcy) concentration or carotid intimal-media wall thickness (IMT), an early marker of atherosclerosis, in these patients. RESEARCH DESIGN AND METHODS—We measured plasma IL-18 in 103 type 2 diabetic patients and 45 age-matched control subjects. We also measured patients’ plasma tHcy and serum high-sensitivity C-reactive protein (hs-CRP). IMT was evaluated for both common carotid arteries. RESULTS—Plasma IL-18 was significantly higher in diabetic patients than in control subjects (203 ± 153 vs. 118 ± 37 pg/ml, P &amp;lt; 0.001). High IL-18 was defined as equaling or exceeding the mean + 2 SD of plasma IL-18 in control subjects (192 pg/ml). Patients with high IL-18 showed a greater carotid IMT than those with normal IL-18. Carotid plaques were more numerous in diabetic patients with high IL-18 than in those with normal IL-18. Plasma tHcy concentrations were significantly higher in patients with high IL-18 than in those with normal IL-18. Univariate and multivariate analyses showed a strong independent association between tHcy and IL-18. Plasma IL-18 also correlated positively with serum hs-CRP. CONCLUSIONS—In patients with type 2 diabetes, plasma IL-18 concentrations are greater than in nondiabetic subjects. Plasma IL-18 is an independent determinant of plasma tHcy, which is linked independently with atherosclerotic carotid wall thickening.
Major Changes Made by Criteria Committee of the New York Heart Association
Authors: R. M. HARVEY, E. F. DOYLE, K. ELLIS, S. J. FARBER, M. I. FERRER, E. E. FISCHEL, A. C. FOX, S. P. GRIFFITHS, A. G. JAMESON, T. KILLIP, M. KUSCHNER, J. R. MALM
Journal: Circulation (1974)
Rupture of the Gastroduodenal Artery
Authors: James W. Sampsell
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Isolated injury of vessels within the abdomen accompanying a crushing injury is rare, but specific rupture of mesenteric arteries,<sup>1</sup>aorta, vena cava, and mesenteric veins<sup>2</sup>have been reported. This communication records a bizarre and isolated tear of the gastroduodenal artery giving rise to massive hemorrhage. <h3>Report of a Case:—</h3> A 30-year-old man was admitted to the emergency room after an automobile accident; the patient had been drinking beer, and no satisfactory explanation of the mechanism of injury was obtainable. It was known that he was seated to the right of the driver when the car went of the road and turned over. The seat belt was not in use. The patient was pale, distressed, and in obvious shock with a systolic blood pressure of 60 mm Hg. He complained of pain in the right side of the abdomen and increasing pain in the left shoulder.
Modeling to incorporate defense mechanisms into the estimation of dose responses.
Authors: R L Sielken, D E Stevenson
Journal: Environmental Health Perspectives (1998)

Several adverse health effects (including cancer and noncancer effects) may be the result of an imbalance between exogenous and endogenous invading substances and defense mechanisms. In these cases the probability of an adverse effect depends on how much the exposure to a substance increases or decreases the number of defenders or their efficiency as well as increasing or decreasing the number of invaders. Rather than using a dose scale such as parts per million or milligram/kilogram/day in these cases, dose-response models can directly incorporate the impact of defense mechanisms by using a dose scale that corresponds to the number of invaders that break through the defenders and become free to do their damage. The number of breakthroughs at a specific age, the cumulative number of breakthroughs by a specific age, or the cumulative number of breakthroughs in a window of time would usually be the appropriate age-dependent dose. Although a lifetime average daily dose level can be used as a surrogate for an age-dependent dose in simplistic dose-response models, the age-dependent dose itself can be used in more biologically based models that include time, reflect the key role of feedback mechanisms, and treat the human body as an age-dependent dynamic system responding to internal and external stimuli and not as a system at equilibrium. Some illustrative biologic examples of defense mechanisms and invader-defender interactions are presented. Several numerical examples are given in which the dose incorporates the age-dependent effects of a substance on the number of invaders, the number of defenders, and/or the defenders' efficiencies.
Physician, Heal Thyself
Authors: Howard Markel
Journal: JAMA (2009)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Physicochemical determinants in hepatic extraction of small peptides
Authors: Ellen B. Hunter, Stephen P. Powers, Louis J. Kost, Delia I. Pinon, Laurence J. Miller, Nicholas F. LaRusso
Journal: Hepatology (1990)

Although the liver is known to extract amino acids and organic anions by well–characterized transport systems, the factors that regulate the hepatic uptake of small, circulating peptides are poorly understood. We previously reported that cholecystokinin octapeptide, a biologically active form of cholecystokinin, is efficiently cleared by the liver and that uptake depends on its carboxyl–terminal tetrapeptide (Trp–Met–Asp–PheNH 2 ). Here we further define the physicochemical determinants for hepatic clearance of cholecystokinin. A series of 13 tetrapeptides, including eight analogs of the carboxyl–terminal tetrapeptide of cholecystokinin–8 with different charges, hydrophobicity and aminoacid sequences, were prepared by solid–phase synthesis, purified by high–performance liquid chromatography and characterized by amino–acid analysis and mass spectrometry. Radioiodination was performed by oxidative or nonoxidative techniques. Hydrophobicity of individual radiolabeled peptides was calculated using published hydrophobicity data or measured directly by determining their partition between octanol and aqueous triethylammonium acetate. First–pass hepatic extraction of radiolabeled peptides was determined with a nonrecirculating, isolated, perfused rat liver model. First–pass hepatic extraction of injected, labeled peptides varied from 4% to 86% and correlated significantly (r = 0.85; p &lt; 0.0002) with hydrophobicity. Hydrophobic peptides with positive, neutral or negative charges were avidly extracted (30% to 86%) by the liver; first–pass clearance of hydrophobic peptides with similar charges varied with amino–acid sequence. In contrast, the first–pass hepatic extraction of positively or negatively charged hydrophilic tetrapeptides was negligible (&lt;10%). These results suggest that hydrophobicity and amino–acid sequence-but not anionic or cationic nature-are the major determinants of hepatic extraction of cholecystokinin, and perhaps other small, circulating peptides. (Hepatology 1990;12:76-82).
Differences in Survival Between Black and White Patients With Diabetic End-Stage Renal Disease
Authors: Catherine C Cowie, Friedrich K Port, Keith F Rust, Maureen I Harris
Journal: Diabetes Care (1994)

OBJECTIVE To evaluate whether the longer survival of blacks with diabetic end-stage renal disease (ESRD) relative to whites is due to racial differences in type of diabetes, comorbidity at ESRD onset, and ESRD treatment modality and to examine whether survival differences between blacks and whites occur only in certain population subgroups. RESEARCH DESIGN AND METHODS The Michigan Kidney Registry was used to ascertain all blacks and whites (n = 594) with diabetic ESRD in southeastern Michigan, with ESRD onset at age &amp;lt;65 years during 1974–1983. Patients were followed through 1988. Medical records were abstracted for type of diabetes, comorbidity at ESRD onset, and other factors. RESULTS Median survival among insulin-dependent diabetes mellitus patients was 27 months in blacks and 17 months in whites, and among non-insulin-dependent diabetes mellitus patients was 30 months in blacks and 16 months in whites. After adjustment for confounding factors by Cox proportional hazards analysis, the death rate was 45% lower in blacks than in whites on dialysis (relative death rate [RDR] = 0.55,95% confidence interval [CI] = 0.44–0.69), but was similar in blacks and whites with a renal transplant (RDR = 0.99, 95% CI = 0.64–1.52). Compared with dialysis, transplantation was associated with lower mortality in both races (whites, RDR = 0.50, 95% CI = 0.36–0.70; blacks, RDR = 0.89, 95% CI = 0.60–1.34), although the effect was not statistically significant in blacks. Racial differences in survival did not vary by type of diabetes or any additional factor. CONCLUSIONS Survival after ESRD onset is longer in blacks than in whites treated with dialysis, even after adjusting for comorbidity and other factors that affect survival. Survival does not differ by race among transplant patients.
Human immunodeficiency virus infection down-regulates HLA class II expression and induces differentiation in promonocytic U937 cells.
Authors: A J Petit, F G Terpstra, F Miedema
Journal: Journal of Clinical Investigation (1987)

We studied the effect of human immunodeficiency virus (HIV) infection on the surface-marker expression of the human promonocytic cell line U937. U937 cells persistently produced HIV as detected by reverse transcriptase activity in culture supernatant. Expression of HLA class II antigens on U937/HIV cells was decreased 2- to 10-fold, depending on the Mab used. Class II expression of U937/HIV cells increased approximately two-fold by treatment with r-interferon-gamma. Whereas noninfected U937 cells expressed moderate amounts of lymphocyte function-associated antigen-1 (LFA-1) (CD11a) and minimal amounts of the C3bi receptor (CD11b) and p150/95 (CD11c), U937/HIV cells expressed moderate amounts of C3bi receptor and p150/95 and showed elevated expression of LFA-1 alpha (CD11a) and -beta (CD18) chains. Expression of these adhesion molecules resulted in strongly enhanced phorbolester-induced aggregation of U937/HIV cells compared with the noninfected U937 cells. In addition, almost all U937/HIV cells, but not noninfected U937 cells, intensely stained for cytoplasmic nonspecific esterase activity. The effects of HIV infection on U937 cells strikingly resemble the effects of differentiation-inducing agents, such as PMA and DMSO, on the U937 phenotype. Our finding suggests that HIV infection, apart from down regulating class II expression, induces differentiation of U937 cells.
Coxsackie-adenovirus-receptor induction is associated with enteroviral and adenoviral infection in acute myocarditis and dilated cardiomyopathy
Authors: Michel Noutsias, Wolfgang C. Poller, Henry Fechner, Felicitas Escher, Heinz P. Schultheiss, Matthias Pauschinger
Journal: Journal of the American College of Cardiology (2003)
The preparation and evaluation of poly(ϵ-caprolactone) microparticles containing both a lipophilic and a hydrophilic drug
Authors: Mónica Hombreiro Pérez, Colette Zinutti, Alf Lamprecht, Nathalie Ubrich, Alain Astier, Maurice Hoffman, Roland Bodmeier, Philippe Maincent
Journal: Journal of Controlled Release (2000)
Temporal Variability of Pesticide Concentrations in Homes and Implications for Attenuation Bias in Epidemiologic Studies
Authors: Nicole C. Deziel, Mary H. Ward, Erin M. Bell, Todd P. Whitehead, Robert B. Gunier, Melissa C. Friesen, John R. Nuckols
Journal: Environmental Health Perspectives (2013)

Background: Residential pesticide exposure has been linked to adverse health outcomes in adults and children. High-quality exposure estimates are critical for confirming these associations. Past epidemiologic studies have used one measurement of pesticide concentrations in carpet dust to characterize an individual's average long-term exposure. If concentrations vary over time, this approach could substantially misclassify exposure and attenuate risk estimates.Objectives: We assessed the repeatability of pesticide concentrations in carpet dust samples and the potential attenuation bias in epidemiologic studies relying on one sample.Methods: We collected repeated carpet dust samples (median = 3; range, 1–7) from 21 homes in Fresno County, California, during 2003–2005. Dust was analyzed for 13 pesticides using gas chromatography–mass spectrometry. We used mixed-effects models to estimate between- and within-home variance. For each pesticide, we computed intraclass correlation coefficients (ICCs) and the estimated attenuation of regression coefficients in a hypothetical case–control study collecting a single dust sample.Results: The median ICC was 0.73 (range, 0.37–0.95), demonstrating higher between-home than within-home variability for most pesticides. The expected magnitude of attenuation bias associated with using a single dust sample was estimated to be ≤ 30% for 7 of the 13 compounds evaluated.Conclusions: For several pesticides studied, use of one dust sample to represent an exposure period of approximately 2 years would not be expected to substantially attenuate odds ratios. Further study is needed to determine if our findings hold for longer exposure periods and for other pesticides.
2-AMINO-3 (METHYLAMINO)-PROPIONIC ACID IN CYCAD-DERIVED FOODS IS AN UNLIKELY CAUSE OF AMYOTROPHIC LATERAL SCLEROSIS/PARKINSONISM
Authors: MarkW. Duncan, IrwinJ. Kopin, RalphM. Garruto, Lawrence Lavine, SanfordP. Markey
Journal: The Lancet (1988)
Doctors should do as they're told – myth or reality?
Authors: Andrew Papanikitas
Journal: Journal of the Royal Society of Medicine (2009)

The end of the 20th century has seen the endorsement of patient-centeredness as a core component of any clinical consultation. Doctors working within or contracted to the NHS are increasingly seen less as autonomous professionals and more as civil servants, answering to a number of masters. In the post-millennial NHS where do the boundaries of personal and professional autonomy lie?
Pandemic avian influenza
Authors: Leonard A Mermel
Journal: The Lancet Infectious Diseases (2005)

In 1918, Philadelphia medical schools dismissed students to assist in caring for the onslaught of influenza-infected patients in local hospitals. One such student was Isaac Starr, who wrote a chilling description of what he observed: "After gasping for several hours they became delirious and incontinent, and many died struggling to clear their airways of a blood-tinged froth that sometimes gushed from their nose and mouth".1 86 years later, the pathophysiological basis of Starr's description has been elucidated.
Alterations in Lumbar Cerebrospinal Fluid Protein During Air Encephalography
Authors: J. R. W. Dykes, D. L. Stevens
Journal: BMJ (1970)

A significant fall occurred in the protein content of successive specimens of lumbar cerebrospinal fluid (C.S.F.) withdrawn during the course of air encephalography in 57% of cases. No correlation was found between the fall in the protein concentration and the total volume of air injected or the total volume of C.S.F. withdrawn, but the size of the fall was greater when the initial lumbar C.S.F. protein concentration was raised. The importance of taking specimens for routine laboratory analysis before the injection of any air is emphasized.
Disability assessment medicine
Authors: M. Aylward, P. Sawney
Journal: BMJ (1999)

Disability assessment medicine is the specialty primarily concerned with the medical assessment of individuals in order to provide objective medical advice to decision makers. These decision makers may be benefit administrators, employers, or "finders of fact" in the insurance industry. Disability assessment is also a key part of advising employers in relation to the Disability Discrimination Act 1995 and local authorities in relation to the provision of community care services. In carrying out this function, doctors act as specialist medical disability analysts. The role of a disability analyst differs from the more familiar clinical role of reaching a diagnosis and arranging treatment: the disability analyst's primary function is to make an assessment of how a person is affected by his or her disease or disability and to relate this to the legislative or policy requirements or the specific issues raised by the decision maker. Disability analysts also have an important role to play in educating health professionals and managers about disability issues. #### Decision makers in disability assessment ##### Who is a decision maker? The decision maker is usually the "finder of fact," who decides a question (say of entitlement to a benefit or service) by weighing the available evidence in accordance with the relevant legislation or policy specification #### What decision makers expect from a medical report The following elements are considered essential: #### Pros and cons of disability assessment medicine ##### Advantages
Herpes Zoster and Steroid Therapy
Authors: A. Fry
Journal: BMJ (1963)

but in whom a diagnosis of pyelonephritis is subsequently established.It has also been shown that to examine the urinary deposit for white cells in the way they describe may be misleading.2And it is well known that the urine may be infected even if there is no increase in the number of white cells present.3 4 The difficulties of quantitative pour-plate cultures have perhaps been over-emphasized by those less experienced in this technique.We have found that a competent technician can perform up to 20 such cultures in an hour.-Weare, etc.,
Defective NK Cell Activity and Th1 Response in IL-18–Deficient Mice
Authors: Kiyoshi Takeda, Hiroko Tsutsui, Tomohiro Yoshimoto, Osamu Adachi, Nobuaki Yoshida, Tadamitsu Kishimoto, Haruki Okamura, Kenji Nakanishi, Shizuo Akira
Journal: Immunity (1998)
1123-179 Comparison between rescue surgical embolectomy and repeat thrombolysis after unsuccessful thrombolysis in acute pulmonary embolism
Authors: Nicolas Meneveau, Luc Lorgis, Pierre Legalery, Marie-France Seronde, Florent Briand, Francois Schiele, Yvette Bernard, Jean-Pierre Bassand
Journal: Journal of the American College of Cardiology (2004)