tbuckley/cabot-search huggingface dataset:
Frequent Inactivation of PTEN by Promoter Hypermethylation in Microsatellite Instability-High Sporadic Colorectal Cancers
Authors: Ajay Goel, Christian N. Arnold, Donna Niedzwiecki, John M. Carethers, Jeannette M. Dowell, Linda Wasserman, Carolyn Compton, Robert J. Mayer, Monica M. Bertagnolli, C. Richard Boland
Journal: Cancer Research (2004)

Abstract Loss of PTEN tumor suppressor function is observed in tumors of breast, prostate, thyroid, and endometrial origin. Allelic losses in the proximity of the PTEN locus (10q23) also occur in sporadic colorectal cancers (CRCs), but biallelic inactivation of this site has not been frequently demonstrated. We hypothesized that alternative mechanisms of PTEN allelic inactivation, such as promoter hypermethylation, might be operative in CRC and that PTEN inactivation may be related to recognized forms of genomic instability. We characterized a cohort of 273 sporadic CRCs by determining their microsatellite instability (MSI) status. Of these, 146 cancers were examined for PTEN promoter methylation by methylation-specific PCR. Mutations at the poly(A)6 repeat sequences in PTEN exons 7 and 8 and deletions at the 10q23 locus were also identified using microsatellite analysis. The presence of PTEN protein was determined by immunostaining, and the results were correlated with the promoter methylation status. We observed that PTEN promoter hypermethylation was a frequent occurrence in MSI-high (MSI-H) tumors (19.1% of MSI-H versus 2.2% of MSI-low/microsatellite stable tumors; P = 0.002). A PTEN mutation or a deletion event was present in 60% of the tumors with promoter region hypermethylation. Hypermethylation of the PTEN promoter correlated significantly with either decreased or complete loss of PTEN protein expression (P = 0.004). This is the first demonstration of PTEN inactivation as a result of promoter hypermethylation in MSI-H sporadic CRCs. These data suggest that this silencing mechanism plays a major role in PTEN inactivation and, in colon cancer, may be more important than either allelic losses or inactivating mutations. The significant correlation of PTEN hypermethylation with MSI-H tumors further suggests that PTEN is an additional important “target” of methylation along with the hMLH1 gene in the evolution of MSI-H CRCs and also confers the “second hit” in the biallelic inactivation mechanism for some proportion of tumors.
Inhibition of rat hepatic mitochondrial aldehyde dehydrogenase-mediated acetaldehyde oxidation by trans-4-hydroxy-2-nonenal
Authors: D Mitchell
Journal: Hepatology (1991)

The hepatic oxidation of ethanol has been demonstrated to cause peroxidation of cellular membranes, resulting in the production of aldehydes that are substrates for hepatic aldehyde dehydrogenases. It was the purpose of this study to evaluate the cooxidation of the lipid peroxidation product, trans-4-hydroxy-2-nonenal, and acetaldehyde by high-affinity mitochondrial aldehyde dehydrogenase, which is of prominent importance in the oxidation of ethanol-derived acetaldehyde. Experiments were performed for determination of kinetic parameters for uninhibited acetaldehyde and 4-hydroxynonenal oxidation by semi-purified mitochondrial aldehyde dehydrogenase prepared from male Sprague-Dawley rat liver. The affinity of the enzyme for the substrate at low substrate concentrations and the Michaelis-Menten constant of mitochondrial aldehyde dehydrogenase for acetaldehyde were 25 and 10 times greater, respectively, than those determined for 4-hydroxynonenal. Coincubation of acetaldehyde with physiologically relevant concentrations of 4-hydroxynonenal (0.25 to 5.0 mumol/L) with mitochondrial aldehyde dehydrogenase demonstrated that 4-hydroxynonenal is a potent competitive or mixed-type inhibitor of acetaldehyde oxidation, with concentration of 4-hydroxynonenal required for a twofold increase in the slope of the Lineweaver-Burk plot for acetaldehyde oxidation by ALDH of 0.48 mumol/L. The results of this study suggest that the aldehydic lipid peroxidation product, trans-4-hydroxy-2-nonenal, is a potent inhibitor of hepatic acetaldehyde oxidation and may potentiate the hepatocellular toxicity of acetaldehyde proposed to be an etiological factor of alcoholic liver disease.
Measurement of Cardiac Output by Thermodilution with Constant Rate Injection of Indicator
Authors: K. PÁVEK, D. BOSKA, F. V. SELECKÝ, A. Sauberer
Journal: Circulation Research (1964)

A mathematical formula has been suggested for measurement of cardiac output by the thermodilution technique using constant rate indicator injection. The theoretical assumptions have been checked in model experiments and in experiments on dogs. The best reproducibility was attained when the indicator was injected into the right atrium, near the tricuspid valve, and the dilution was detected in the pulmonary artery. Recirculation of the cool indicator is negligible and takes place only after the attainment of the curve plateau. No systematic difference was found in simultaneous measurements made by the Fick principle and the injection technique. The correlation coefficient, r , was 0.96.
Proliferation and extracellular matrix synthesis of smooth muscle cells cultured from human coronary atherosclerotic and restenotic lesions
Authors: Donald C. MacLeod, Bradley H. Strauss, Marcel de Jong, Javier Escaned, Victor A. Umans, Robert-Jan van Suylen, Anton Verkerk, Pim J. de Feyter, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (1994)
Rheumatoid Factors in Graves' Disease
Authors: JAY SILVERBERG
Journal: Annals of Internal Medicine (1978)

Brief Reports1 February 1978Rheumatoid Factors in Graves' DiseaseJAY SILVERBERG, M.D., F.R.C.P.(C), VAS V. ROW, M.A., M.SC., ROBERT VOLPÉ, M.D., F.R.C.P.(C), F.A.C.P.JAY SILVERBERG, M.D., F.R.C.P.(C)Search for more papers by this author, VAS V. ROW, M.A., M.SC.Search for more papers by this author, ROBERT VOLPÉ, M.D., F.R.C.P.(C), F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-88-2-216 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCurrently, Graves' disease is considered to have an immune basis (1). Numerous disturbances in cellular and humoral immunity have been documented in patients with Graves' disease; some such changes are specific, whereas others have been nonspecific. Rheumatoid factors are a family of antiglobulins directed against the Fc' fragment of human IgG molecules (2). Classically rheumatoid factors are detected in the serum of patients with rheumatoid arthritis; however, they may be found in the serum of patients with other disorders in which the immune system plays some role (3). Normal persons, especially the elderly, may also have low titres of rheumatoid...References1. VOLPÉ R: The role of autoimmunity in hypoendocrine and hyperendocrine function. Ann Intern Med 87:86-99, 1977 LinkGoogle Scholar2. STAGEMANNEK DM: Rheumatoid factors in rheumatoid arthritis. Bull Rheum Dis 1972-1973 series, 23, No. 7, pp. 720-725 MedlineGoogle Scholar3. HOWELLMALCOLMPIKE DJR: The F11 agglutinating factors in serums of patients with non-rheumatic diseases. Am J Med 29:662-671, 1960 CrossrefMedlineGoogle Scholar4. HOLLENDERMCCARTY JD (eds): Arthritis and Allied Conditions. Philadelphia, Lea & Febiger, 1972 Google Scholar5. SINGERPOLTZ JG: The latex fixation test: test I, application to the serologic diagnosis of rheumatoid arthritis; test II, result in rheumatoid arthritis. Am J Med 21:888-896, 1956 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Wellesley Hospital University of Toronto Toronto, Ontario Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByAcute pericarditis: a rare complication of Graves' thyrotoxicosis?Experimental modelsAuto-immunity in Thyroid DiseaseRheumatoid Arthritis in HyperthyroidismHERBERT E. COHEN, M.D., F.A.C.P. 1 February 1978Volume 88, Issue 2Page: 216-217KeywordsElderlyHumoral immunityImmune systemRheumatoid arthritis Issue Published: 1 February 1978 PDF DownloadLoading ...
The Effect of Gaps in Health Insurance on Continuity of a Regular Source of Care Among Preschool-aged Children in the United States
Authors: Michael D. Kogan
Journal: JAMA (1995)

<h3>Objective.</h3> —To estimate the prevalence and length of gaps in health insurance coverage and their effect on having a regular source of care in a national sample of preschool-aged children. <h3>Design.</h3> —Follow-up survey of a nationally representative sample of 3-year-old children in the US population by phone or personal interview. <h3>Participants.</h3> —A total of 8129 children whose mothers were interviewed for the 1991 Longitudinal Follow-up to the National Maternal and Infant Health Survey. <h3>Main Outcome Measures.</h3> —Report of any gap in health insurance for the children, the length of the gap, and the number of different sites where the children were taken for medical care as a measure of continuity of a regular source of care. <h3>Results.</h3> —About one quarter of US children were without health insurance for at least 1 month during their first 3 years of life. Over half of these children had a health insurance gap of more than 6 months. Less than half of US children had only one site of care during their first 3 years. Children with health insurance gaps of longer than 6 months were at increased risk of having more than one care site (odds ratio = 1.52; 95% confidence interval, 1.19 to 1.96). This risk further increased when an emergency treatment was discounted as a multiple site of care. <h3>Conclusions.</h3> —Having a gap in health insurance coverage is an important determinant for not having a regular source of care for preschool-aged children. This finding is of concern, given the sizable percentage of children in the United States who lacked continuous health care coverage during a critical period of development. (<i>JAMA</i>. 1995;274:1429-1435)
Injection Site Effects on the Pharmacokinetics and Glucodynamics of Insulin Lispro and Regular Insulin
Authors: Edith W Ter Braak, James R Woodworth, Rutgert Bianchi, Benito Cerimele, D Willem Erkelens, Jos H H Thijssen, Darcie Kurtz
Journal: Diabetes Care (1996)

OBJECTIVE The pharmacokinetics and glucodynamics of a new insulin analog, insulin lispro, and regular human insulin were compared and contrasted after subcutaneous administrations in femoral, deltoid, and abdominal injection sites. RESEARCH DESIGN AND METHODS Single 0.2 U/kg doses of insulin lispro and regular insulin were administered to 12 healthy subjects in a six-way randomized crossover fashion. Each dose was given after an overnight fast in one of three injection sites: abdominal, deltoid, or femoral. Study drugs were given during a manual euglycemic glucose clamp. Blood samples were collected over the 12-h clamp for measurement of insulin-reactive components, with pharmacokinetic and glucodynamic measurements derived from these serum insulin and clamp measurements. RESULTS Glucodynamic comparisons between insulin lispro and regular insulin showed a greater maximum infusion rate (Rmax) at an earlier time (TRmax), regardless of injection site. The total glucose infused (Gtot) showed nearly identical values between sites for insulin lispro. Regular insulin showed greater Gtot values from deltoid and femoral injections. When comparisons were made between drugs, regular insulin produced significantly greater Gtot, primarily driven by the increased Gtot from deltoid and femoral injections. Greater maximum serum insulin concentrations (Cmax) were experienced with insulin lispro at earlier times (tmax), regardless of the injection site (P &amp;lt; 0.001). Abdominal administrations produced the greatest Cmax values at the earliest tmax for both regular insulin and insulin lispro. Deltoid and femoral injections had lower Cmax values for both compounds. Shifts also occurred with tmax, although these shifts were much greater with regular insulin than with insulin lispro. Equivalent area under the curve (AUC) values were found when compared between compounds. CONCLUSIONS Slower absorption from deltoid and femoral administrations resulted in an increased duration of action for both regular insulin and insulin lispro when compared to abdominal administration. However, notable increases in the onset of action were only apparent with regular insulin. The consistency with insulin lispro response from abdominal and extremity injection sites allows more potential sites for subcutaneous injection with an assured rapid response.
Diphtheria in an Elderly Woman: Unexpected Sequelae
Authors: L Robinson, B S Azadian, F Rahaman, I Zamiri
Journal: Journal of the Royal Society of Medicine (1987)

0141-0768/87/ 090584-02/$02.00/0 i 1987 The Royal Society of Medicine Case report The patient was a 70-year-old widow who lived alone, had no relatives and had not been abroad recently. She had never been immunized. She was admitted with a four-day history of sore throat, hoarse voice, marked dysphagia, trismus and swollen tender cervical lymph nodes. Her throat was inflamed and there appeared to be a right parafollicular abscess. No membrane was observed. She was afebrile and remained so throughout her illness. A right quinsy with dehydration was diagnosed. A throat swab was taken and she was rehydrated and treated with intravenous flucloxacillin and metronidazole. Three days later the patient developed a palatal vpalsy and slight nasal regurgitation on attempting to swallow. She was isolated when a coryneform organism cultured from the throat swab made a diagnosis of diphtheria likely. The organism was identified as a toxigenic Corynebacterium diphtheriae var mitis. The patient's antibiotic therapy was changed to erythromycin and she was transferred to the Regional Isolation Unit. Coryneform organisms isolated from a screening throat swab from the ENT house officer who was attending the patient were subcultured onto Tinsdale's medium'. These organisms produced colonies surrounded by brown haloes, denoting presumptive C. diphtheriae. When contacted, the house officer said she felt unwell and had a sore throat. She too was admitted to the Regional Isolation Unit. On admission she had a temperature of 380C. There was
Detecting alcoholism. The CAGE questionnaire
Authors: J. A. Ewing
Journal: JAMA (1984)

Four clinical interview questions, the CAGE questions, have proved useful in helping to make a diagnosis of alcoholism. The questions focus on Cutting down, Annoyance by criticism, Guilty feeling, and Eye-openers. The acronym "CAGE" helps the physician to recall the questions. How these questions were identified and their use in clinical and research studies are described.
Investor-Owned Chains and Teaching Hospitals
Authors: Gerard F. Anderson, Carl J. Schramm, Catherine R. Rapoza, Steven C. Renn, George D. Pillari
Journal: New England Journal of Medicine (1985)

Within the academic medical community, there is concern about the future economic viability of teaching hospitals. Numerous studies, congressional hearings, and conferences have explored the problem of how teaching hospitals can cope with a changing financial environment. At the same time, investor-owned chains are actively acquiring teaching hospitals and paying premium prices for these institutions. Although the phenomenon is relatively new, if it grows, it could have important public-policy ramifications for medical education, biomedical research, and the development and testing of new medical technology.In recent months several sales or leases of major university-affiliated teaching hospitals to proprietary chains have . . .
A Model Society.
Authors: T. D. Crothers
Journal: JAMA (1900)

Hartford, Conn., July 18, 1900. <h3>To the Editor:</h3> —Medical societies and their progress are always subjects of interest. The Thurber Medical Society is a model and in some ways an object-lesson of great value. The town of Milford, in Worcester County, Mass., had a very noted physician many years ago. He was not only a physician of eminence, but one who made friends, and was literary in his tastes. In 1853 a little group of physicians formed a society for medical improvement and the cultivation of good fellowship, and named it after him. They soon began to collect a library, and received donations from outside, and became incorporated by an act of the legislature. This society has been in existence up to the present time. One hundred and eleven persons are numbered among its members during these years. The average attendance at each meeting is from fifteen to thirty, and
The Complete Mitochondrial DNA Sequence of Mesostigma viride Identifies This Green Alga as the Earliest Green Plant Divergence and Predicts a Highly Compact Mitochondrial Genome in the Ancestor of All Green Plants
Authors: Monique Turmel, Christian Otis, Claude Lemieux
Journal: Molecular Biology and Evolution (2002)

To gain insights into the nature of the mitochondrial genome in the common ancestor of all green plants, we have completely sequenced the mitochondrial DNA (mtDNA) of Mesostigma viride. This green alga belongs to a morphologically heterogeneous class (Prasinophyceae) that includes descendants of the earliest diverging green plants. Recent phylogenetic analyses of ribosomal RNAs (rRNAs) and concatenated proteins encoded by the chloroplast genome identified Mesostigma as a basal branch relative to the Streptophyta and the Chlorophyta, the two phyla that were previously thought to contain all extant green plants. The circular mitochondrial genome of Mesostigma resembles the mtDNAs of green algae occupying a basal position within the Chlorophyta in displaying a small size (42,424 bp) and a high gene density (86.6% coding sequences). It contains 65 genes that are conserved in other mtDNAs. Although none of these genes represents a novel coding sequence among green plant mtDNAs, four of them (rps1, sdh3, sdh4, and trnL[caa]) have not been reported previously in chlorophyte mtDNAs, and two others (rpl14 and trnI[gau]) have not been identified in the streptophyte mtDNAs examined so far (land-plant mtDNAs). Phylogenetic analyses of 19 concatenated mtDNA-encoded proteins favor the hypothesis that Mesostigma represents the earliest branch of green plant evolution. Four group I introns (two in rnl and two in cox1) and three group II introns (two in nad3 and one in cox2), two of which are trans-spliced at the RNA level, reside in Mesostigma mtDNA. The insertion sites of the three group II introns are unique to this mtDNA, suggesting that trans-splicing arose independently in the Mesostigma lineage and in the Streptophyta. The few structural features that can be regarded as ancestral in Mesostigma mtDNA predict that the common ancestor of all green plants had a compact mtDNA containing a minimum of 75 genes and perhaps two group I introns. Considering that the mitochondrial genome is much larger in size in land plants than in Mesostigma, we infer that mtDNA size began to increase dramatically in the Streptophyta either during the evolution of charophyte green algae or during the transition from charophytes to land plants.
Selective Smallpox Vaccination for Special Risk Groups
Authors: Reuben Tizes
Journal: JAMA (1974)

To the Editor.—  The  line of  in the event of a smallpox importation into the United States consists of attention to hospital and health personnel and to travelers to and from the smallpox infected areas, according to a personal communication from D. J. Sencer in March 1974. It was recommended 1 that these high-risk groups be vaccinated against smallpox and that a high level of immunity be maintained by repeating vaccinations every three years. One wonders as to the effectiveness and practicability of these recommendations in terms of actual implementation. What is the percentage of vaccinations and revaccinations for hospital and health personnel? Is this information being collected and monitored? Is it possible that these recommendations are unworkable and that the United States does not have in fact a first line of defense in the event of a smallpox importation? Could it be that its effectiveness will be
Primary lymphadenopathy complicating idiopathic steatorrhoea.
Authors: R Whitehead
Journal: Gut (1968)

<h3>Abstract</h3> What, if any, dividends do agencies reap from collaboration with a highly reputable agency, such as the FDA? Utilizing a dataset covering 30 U.S. federal agencies over a period of 34 years (1980–2013), we estimate the short and long-term reputational effects of interagency collaboration. Collaboration is measured by the number of memorandums of understanding (MOUs) in effect between each agency and the FDA, while agency reputation is assessed using an automated measure of media-coverage valence (positive/negative tone) for each agency-year. To account for potential reverse and reciprocal causality, we utilize cross-lagged fixed-effects models. We find evidence of moderate rises in reputation due to increased collaboration with the FDA. These effects persist significantly for two years, before decaying to null after four years. Employing similar analyses, we furthermore estimate reversed causality – of reputation on the level of consequent collaboration – finding no evidence of such effects. <h3>Research Support</h3> Moshe Maor and Raanan Sulitzeanu-Kenan gratefully acknowledge financial support from the Israel Science Foundation under grant 1002/11.
Multiple Facets of NF-κB in the Heart
Authors: Joseph W. Gordon, James A. Shaw, Lorrie A. Kirshenbaum
Journal: Circulation Research (2011)

The progression from cardiac injury to symptomatic heart failure has been intensely studied over the last decade, and is largely attributable to a loss of functional cardiac myocytes through necrosis, intrinsic and extrinsic apoptosis pathways and autophagy. Therefore, the molecular regulation of these cellular programs has been rigorously investigated in the hopes of identifying a potential cell target that could promote cell survival and/or inhibit cell death to avert, or at least prolong, the degeneration toward symptomatic heart failure. The nuclear factor (NF)-κB super family of transcription factors has been implicated in the regulation of immune cell maturation, cell survival, and inflammation in many cell types, including cardiac myocytes. Recent studies have shown that NF-κB is cardioprotective during acute hypoxia and reperfusion injury. However, prolonged activation of NF-κB appears to be detrimental and promotes heart failure by eliciting signals that trigger chronic inflammation through enhanced elaboration of cytokines including tumor necrosis factor α, interleukin-1, and interleukin-6, leading to endoplasmic reticulum stress responses and cell death. The underlying mechanisms that account for the multifaceted and differential outcomes of NF-κB on cardiac cell fate are presently unknown. Herein, we posit a novel paradigm in which the timing, duration of activation, and cellular context may explain mechanistically the differential outcomes of NF-κB signaling in the heart that may be essential for future development of novel therapeutic interventions designed to target NF-κB responses and heart failure following myocardial injury.
Pain in the Neonate
Authors: Anne B. Fletcher
Journal: New England Journal of Medicine (1987)

IT has generally been assumed that the ability of a child to feel pain increases with age and that neonates may not perceive pain or may perceive it only minimally. Assumed by whom? Certainly not by those of us at the bedside of critically ill infants, who see them flinch from procedures, startle in response to loud noises, and turn from bright lights and various other forms of stimulation. Not by those who have heard infants' anguished cries and seen their vigorous withdrawals from painful stimuli. Not by those who have observed their increasing heart and respiratory rates and profuse . . .