tbuckley/cabot-search huggingface dataset:
Survival of Subendocardial Purkinje Fibers after Extensive Myocardial Infarction in Dogs
Authors: PETER L. FRIEDMAN, JAMES R. STEWART, JOHN J. FENOGLIO, ANDREW L. WIT
Journal: Circulation Research (1973)

Alterations in cardiac electrophysiology that accompany myocardial infarction were studied in dogs subjected to a two-stage ligation of the anterior descending coronary artery. A multipolar transmural needle electrode was used to record electrical activity from the in situ infarcted heart 24 hours after coronary occlusion. Bipolar electrograms recorded from subendocardial regions of infarcted myocardium demonstrated the persistence of early, rapid deflections suggesting Purkinje fiber activity; evidence of ventricular muscle activity in the infarct was absent in both subendocardial and intramural electrograms. The infarcted myocardium and the adjacent non-infarcted tissue were then excised and studied with intracellular microelectrodes in vitro. Transmembrane action potentials could be recorded from one or two cell layers of subendocardial Purkinje fibers at all sites within the infarcted region, but no ventricular muscle action potentials were found. Subendocardial Purkinje fibers which survived in the infarct had reduced maximum diastolic potentials, action potential amplitudes, and maximum depolarization velocities compared with normal subendocardial Purkinje fibers; also, action potential durations in these surviving fibers were extraordinarily prolonged. Spontaneous diastolic depolarization was evident in some surviving fibers. Since subendocardial Purkinje fibers that generate abnormal action potentials survive in an infarct, these fibers may participate in the genesis of ventricular arrhythmias that accompany infarction.
Osteoarthrosis of the knee in men and women in association with overweight, smoking, and hormone therapy
Authors: H. Sandmark, C. Hogstedt, S. Lewold, E. Vingard
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVES</h3> The aim was to examine the relation between osteoarthrosis of the knee leading to prosthetic surgery among men and women and overweight, smoking, and hormone therapy. <h3>METHODS</h3> A case-referent study was performed with a study base of all men and women, born 1921–1938, living in 14 counties in Sweden during 1991–95. The cases (n=625) were identified through the Swedish Knee Arthroplasty Register. The referents (n=548) were randomly selected through the central population register from the same counties. Detailed information on general health status, height, weight, smoking habits, medication, use of hormones, specific physical loads from occupation and housework, and sports activities was collected by a telephone interview and a postal questionnaire. The cases were classified in terms of high, medium or low/non-exposure to the factors studied, according to the distribution of variables among the referents. <h3>RESULTS</h3> Women with high body mass index (BMI) at the age of 40 had a relative risk of 9.2 (95%CI 5.3, 16.0) of developing severe knee osteoarthrosis later in life, and for men at the same age the relative risk was 3.9 (95%CI 2.3, 6.4). Smokers were less likely to develop severe knee osteoarthrosis compared with non-smokers. Oestrogen therapy for women over 50 showed an increased relative risk of 1.8 (95%CI 1.2, 2.6), while use of oral contraceptives did not influence the risk . <h3>CONCLUSION</h3> Overweight is a risk factor for knee osteoarthrosis leading to prosthetic surgery in men and women, with the strongest relation for women. Oestrogen therapy after 50 increased the relative risk, while smoking decreased it.
Molecular Remodeling of the Presynaptic Active Zone of Drosophila Photoreceptors via Activity-Dependent Feedback
Authors: Atsushi Sugie, Satoko Hakeda-Suzuki, Emiko Suzuki, Marion Silies, Mai Shimozono, Christoph Möhl, Takashi Suzuki, Gaia Tavosanis
Journal: Neuron (2015)
Association of a precore genomic variant of hepatitis B virus with fulminant hepatitis
Authors: William F. Carman, Elizabeth A. Fagan, Stephanos Hadziyannis, Peter Karayianni, Nicolaos C. Tassopoulos, Roger Williams, Howard C. Thomas
Journal: Hepatology (1991)

A variant of hepatitis B virus has been described recently in HBsAg+ Mediterranean patients who lack HBeAg and who have an unusual and severe form of chronic hepatitis. This variant is unable to produce HBeAg because of the presence of a novel translational stop codon at the end of the precore region of the genome. By direct sequencing of DNA, generated by the polymerase chain reaction, we have evaluated the association between infection with this variant and the fulminant course of hepatitis B. Eighteen patients with fulminant hepatitis B were studied. Of the 15 cases from whose serum viral DNA could be sequenced, the variant was found in the admission sera of 8 of 9 HBeAg- patients but in none of 6 HBeAg+ patients who had fulminant hepatitis B. Patients harboring the variant progressed more rapidly into hepatic encephalopathy, but those infected with the variant strain alone had a greater likelihood of survival than those infected with the normal strain or a mixture. The mutant strain may emerge spontaneously during fulminant hepatitis as occurs in chronic hepatitis B infection during seroconversion from HBeAg to antibody. Alternately, and perhaps less commonly, patients may be infected with the variant ab initio.
Gastrin and gastrin receptor activation: an early event in the adenoma-carcinoma sequence
Authors: A M Smith
Journal: Gut (2000)

<h3>BACKGROUND AND AIMS</h3> Gastrin and the cholecystokinin type B/gastrin receptor (CCKBR) have been shown to be expressed in colorectal adenocarcinoma. Both exogenous and autocrine gastrin have been demonstrated to stimulate growth of colorectal cancer but it is not known if gastrin affects the growth of colonic polyps. The purpose of this study was to determine if gastrin and CCKBR are expressed in human colonic polyps and to determine at which stage of progression this occurs. <h3>METHODS</h3> A range of human colonic polyps was assessed for gastrin and CCKBR gene and protein expression. <h3>RESULTS</h3> Normal colonic mucosa did not express gastrin or CCKBR. Gastrin and CCKBR reverse transcription-polymerase chain reaction products were detected and verified by specific hybridisation with an oligo probe on Southern blots. Gastrin and CCKBR were expressed in 78% and 81% of polyps, respectively. Both genes were coexpressed in 97% of cases. Immunohistochemistry identified progastrin in 91%, glycine extended gastrin 17 in 80%, and amidated gastrin 17 in only 47% of polyps. CCKBR was present in 96% of polyps. Expression of gastrin and CCKBR was seen in all histological types and sizes of polyps. <h3>CONCLUSIONS</h3> This study is the first to show widespread expression of both gastrin and its receptor in colorectal polyps. Their activation occurs early in the adenoma-carcinoma sequence. Gastrin may promote progression through the adenoma-carcinoma sequence.
THE QUESTION OF AUTOINTOXICATION IN ACUTE DEPRESSIVE PSYCHOSES
Authors: Victor C. Myers, Jessie W. Fisher, A. R. Dieffendorf
Journal: American Journal of Psychiatry (1909)

The chemical analyses of the feces revealed nothing which could be called distinctly pathological, though skatole was once found in small quantity (2.6 mgms. per 100 gms. feces) and in many instances the phenol was very high, much higher than that observed by Herter in his cases of advanced anæmia. Herter found the average elimination to be about 9 mgms. while here it was slightly over 20 mgms. Indole was found in traces only. In Case VI strong indications of intestinal putrefaction were obtained from the analyses of the culture media. On one occasion 218 mgms. of indole and 93 mgms. of phenol were obtained from 100 ccm. of culture media. On a later examination in the absence of indole, 3 mgms. of skatole were obtained. In Case IX a marked production of indole was observed in both the plain bouillon and in the plain bouillon and calcium carbonate. In the urine examinations of Cases V, VI and IX, the ethereal sulphates were all high with low sulphate ratios. In these same cases the phenol values were all considerably above the normal, while on some occasions the indican was possibly a little high. Three of the nine cases examined, viz., V, VI, and IX, especially V and VI, gave considerable indication of intestinal putrefaction. The diet of both Cases V and VI was almost exclusively of milk and that makes these observations all the more remarkable. These two cases have both been discharged as recovered, while the condition of Case IX remains stationary, symptoms of mental depression still being exhibited. It would seem that in the psychoses studied, the question of autointoxication or more properly autoinfection was one which should always be considered, at least as an influencing factor; although at the present time the analytical data are insufficient to ascribe definitely certain nervous or other disorders to an autointoxication.
The twin questions of personalized medicine: who are you and whom do you most resemble?
Authors: Isaac S Kohane
Journal: Genome Medicine (2009)

Personalized medicine is typically described as the use of molecular or genetic characteristics to customize therapy. This perspective at best provides an incomplete model of the patient and at worst can lead to grossly inappropriate practices. Personalization of medicine requires two characterizations: a well-grounded understanding of who the patient is and an equally robust understanding of the subpopulation that most resembles that patient in the context of the decisions at hand. These characterizations are readily represented probabilistically and can be used to drive decision-making in a rational manner that maximizes the positive outcomes for the patient.
Prostaglandin E Modulation of the Mitogenic Response of Human T Cells
Authors: John D. Stobo, Michael S. Kennedy, Marc E. Goldyne
Journal: Journal of Clinical Investigation (1979)

Prostaglandins (PG) of the E series, PGE1 and PGE2 (PGEs), can induce elevations of intracellular cyclic AMP (cAMP) among thymus-derived (T) lymphocytes (T cells) and inhibit their reactivity. For example, 0.1 μM of PGEs induces a two- to threefold increase of intracellular cAMP among human peripheral blood T cells and a 20-30% suppression of their blastogenic response to phytohemagglutinin. However, this suppression actually represents the net reactivity of T-cell populations demonstrating quite different responses to PGEs. Fractionation of T-enriched populations on a discontinuous density gradient yields a population of high density cells whose phytohemagglutinin-induced blastogenic response is suppressed 60%; a population of intermediate density cells whose response is suppressed 20%; and a population of low density T cells whose response is not suppressed, but is enhanced 20% by both of the PGEs. The diametrically opposite responses of low and high density T cells to the PGEs is not related to any difference in their intrinsic mitogen reactivity nor is it influenced by interactions with other T cells, bone marrow-derived (B) cells, or monocytes. Moreover, the distinct blastogenic response of low and high density T cells to PGEs does not simply correlate with PGE-mediated activation of adenylate cyclase. PGE2 induced comparable absolute and identical relative increases of intracellular cAMP among the low and high density T cells. Cholera toxin, a potent activator of adenylate cyclase, and exogenous 8-bromo cAMP mimicked the effects of the PGEs on these two T-cell populations. These data demonstrate that T cells are heterogeneous with regard to their response to the PGEs. Thus, PGEs should be considered as potential regulators rather than as universal suppressors for T-cell reactivity. Moreover, the effect of PGEs on the blastogenic response of a given T-cell population depends upon intracellular events which occur subsequent to elevations of cAMP.
On a Possible Source of Error in the Diagnosis of Fungus in the Ear
Authors: E. C. Baber
Journal: BMJ (1879)

<b>649</b> <h3><b>Objectives:</b></h3> Labeled white blood cell scintigraphy is used in various clinical conditions. When there is suspicion of an infectious process, especially for bacterial agents, it has high specificity. It can be used in several conditions such as fever of obscure or undetermined origin, osteomyelitis screening and, in cardiology, when there is suspicion of infective endocarditis (IE) associated with the prosthesis. In 2015 it was included in the assessment of suspected IE patient in the Guideline of the European Society of Cardiology (ESC) in 2015. Labeled white blood cell scintigraphy SPECT-CT (WBCS) has demonstrated to be able to reduce the rate of misdiagnosed cases of IE. Few studies are published in a real-world scenario because the technique is not broadly available. The goal of this study is to describe the use of WBCS in a series of consecutive patients in a reference cardiovascular hospital to evaluate the clinical impact in the diagnostic workup of suspected endocarditis. <h3><b>Methods:</b></h3> WBCS was performed at the nuclear medicine service of our institution from January 2015 to August 2017. The clinical indication, type of radiotracer employed, demographic aspects and scintigraphic findings were analyzed. Exams were performed using the in vivo labeling technique with antigranulocyte Besilesomab antibody or with the in vitro labeling of autologous leukocytes with <sup>99m</sup>Tc-HMPAO. The scintigraphic images were performed on SPECT-CT equipment (Symbia T2). Experienced nuclear medicine physicians performed the interpretation of the scans. <h3><b>Results:</b></h3> A total of 138 WBCS were performed in this period, and the majority (108 patients) used the in vitro labeling of autologous leukocytes with HMPAO. Suspected infective endocarditis was responsible for 19% of the clinical indications. The mean age of the patients who underwent endocarditis WBCS was 70 years compared to patients with other indications that had a mean age of 66 years (p = 0.3). There was a predominance of males among patients with suspected endocarditis in relation to other indications (85% x 57%, p = 0.0001). Of the 26 exams requested for endocarditis, 13 (50%) were positive: 5 in prosthetic heart valves, 4 aortic endoprostheses, 2 in mechanical circulatory assist devices. In 2 other cases the examination showed the presence of a non-cardiovascular infectious focus: 1 pulmonary infection and another in the knee joint. Three patients with suspected infection of transcatheter aortic valve implant (TAVI) had negative labeled WBC scans that discarded the TAVI as the focus of infection. <h3><b>Conclusions:</b></h3> The use of WBCS has proved to be useful in the identification of IE in real-world complex cases such as valvular prostheses and vascular endoprostheses. WBCS use should be incorporated in the diagnostic workup of patients with suspected IE when conventional techniques do not yield conclusive results as is recommended by ESC Guideline.
Release of extraction-resistant mRNA in stationary phase Saccharomyces cerevisiae produces a massive increase in transcript abundance in response to stress
Authors: Anthony D Aragon, Gabriel A Quiñones, Edward V Thomas, Sushmita Roy, Margaret Werner-Washburne
Journal: Genome biology (2006)

Abstract Background As carbon sources are exhausted, Saccharomyces cerevisiae cells exhibit reduced metabolic activity and cultures enter the stationary phase. We asked whether cells in stationary phase cultures respond to additional stress at the level of transcript abundance. Results Microarrays were used to quantify changes in transcript abundance in cells from stationary phase cultures in response to stress. More than 800 mRNAs increased in abundance by one minute after oxidative stress. A significant number of these mRNAs encode proteins involved in stress responses. We tested whether mRNA increases were due to new transcription, rapid poly-adenylation of message (which would not be detected by microarrays), or potential release of mature mRNA present in the cell but resistant to extraction during RNA isolation. Examination of the response to oxidative stress in an RNA polymerase II mutant, rpb1-1 , suggested that new transcription was not required. Quantitative RT-PCR analysis of a subset of these transcripts further suggested that the transcripts present in isolated total RNA from stationary phase cultures were polyadenylated. In contrast, over 2,000 transcripts increased after protease treatment of cell-free lysates from stationary phase but not exponentially growing cultures. Different subsets of transcripts were released by oxidative stress and temperature upshift, suggesting that mRNA release is stress-specific. Conclusions Cells in stationary phase cultures contain a large number of extraction-resistant mRNAs in a protease-labile, rapidly releasable form. The transcript release appears to be stress-specific. We hypothesize that these transcripts are associated with P-bodies.
Nuclear factor IA is expressed in astrocytomas and is associated with improved survival
Authors: Hae-Ri Song, Ignacio Gonzalez-Gomez, Greg S. Suh, Deborah L. Commins, Richard Sposto, Floyd H. Gilles, Benjamin Deneen, Anat Erdreich-Epstein
Journal: Neuro-Oncology (2010)

Nuclear factor IA (NFIA) is a transcription factor that specifies glial cell identity and promotes astrocyte differentiation during embryonic development. Its expression and function in gliomas are not known. Here, we examined NFIA protein expression in gliomas and its association with clinical outcome in pediatric malignant astrocytomas. We analyzed expression of NFIA by immunohistochemistry in 88 existing glioma specimens from Childrens Hospital Los Angeles and the University of Southern California. Association between NFIA expression and progression-free survival (PFS) was examined in high-grade astrocytomas for which clinical data were available (n = 23, all children). NFIA was highly expressed in astrocytomas of all grades, but only in a minority of cells in oligodendroglial tumors. NFIA was expressed on a higher percentage of tumor cells in low-grade astrocytomas (91 ± 5% and 77 ± 14% in World Health Organization [WHO] I and II, respectively) compared with high-grade astrocytomas (48 ± 18% and 37 ± 16% in WHO III and IV, respectively; P < .001, low- vs high-grade astrocytomas). There was a significant association between NFIA expression and PFS in children with astrocytoma WHO grade III or IV (Cox regression P = .019; logrank trend test for NFIA tertiles P = .0040 and NFIA quartiles P = .014). The association was not consistently significant in this small series of patients after adjustment was made for WHO grade III or IV. This is the first study to demonstrate expression of NFIA protein in astrocytomas and its association with grades of astrocytoma and PFS, suggesting that NFIA may play a role in astrocytoma biology.
Diurnal changes in serum unconjugated bile acids in normal man.
Authors: K D Setchell, A M Lawson, E J Blackstock, G M Murphy
Journal: Gut (1982)

Unconjugated bile acids were measured using gas chromatography-mass spectrometry in the serum of two subjects throughout a 24 hour period and in two other subjects over a six hour period after breakfast. Unconjugated bile acids were found in all samples of serum and included cholic, chenodeoxycholic, deoxycholic, 3 beta, 7 alpha-dihydroxy-5 beta-cholanic (iso-chenodeoxycholic), ursodeoxycholic, 3 beta, 7 beta-dihydroxy-5 beta-cholanic (iso-ursodeoxycholic), 3 beta-hydroxy-5-cholenoic, and lithocholic acids. The maximum concentration of each bile acid generally occurred between breakfast and dinner and total unconjugated bile acid concentrations attained levels of between 2-3 mumol/l. Concentrations increased after breakfast and were often as high as 30-40% of the conjugated bile acid glycocholate, but returned to fasting levels in the absence of lunch. The intestinal absorption of unconjugated bile acids is therefore of greater quantitative importance than was previously thought.
Preterm Birth—A Risk Factor for Type 2 Diabetes?
Authors: Eero Kajantie, Clive Osmond, David J.P. Barker, Johan G. Eriksson
Journal: Diabetes Care (2010)

The association between low birth weight and type 2 diabetes is well established. We studied whether preterm birth carries a similar risk.The Helsinki Birth Cohort includes 13,345 men and women born between 1934 and 1944. Of them, 12,813 had adequate data on length of gestation, which we linked with data on special reimbursement for diabetes medication.Of the subjects, 5.1% had received special reimbursement after age 40. In subjects born before 35 weeks of gestation, the odds ratio for diabetes was 1.68 (95% CI 1.06-2.65) compared with that in those born at term. After adjustment for birth weight relative to length of gestation, the odds ratio was 1.59 (1.00-2.52).Preterm birth before 35 weeks of gestation is associated with an increased risk of type 2 diabetes in adult life. The risk is independent of that associated with slow fetal growth.
Any questions: Treating resistant otitis externa
Authors: A R. Maw
Journal: BMJ (1997)

<i>What is the treatment for “resistant” otitis externa due to Pseudomonas aeruginosa? My patient has received topical treatment with gentamicin, polymyxin B. ciprofloxacin, 5% acetic acid, 4% aluminium acetate, ceftazidime, meropenem, and intravenous treatment with ceftazidime, and ciprofloxacin. She has partially responded to these but subsequently relapsed, with bilateral green discharge and eczematous skin just around the external ear canal. The ear drums have remained intact and the rest of the ear, nose, and throat examination is normal. The organism is continuously culturable from both ears and has remained fully susceptible to antibiotics with the exception of ciprofoxacin. The patient is in her 20s and in good health; simple immunological tests have been normal.</i>
The Prescription Opioid and Heroin Crisis: A Public Health Approach to an Epidemic of Addiction
Authors: Andrew Kolodny, David T. Courtwright, Catherine S. Hwang, Peter Kreiner, John L. Eadie, Thomas W. Clark, G. Caleb Alexander
Journal: Annual Review of Public Health (2015)

Public health authorities have described, with growing alarm, an unprecedented increase in morbidity and mortality associated with use of opioid pain relievers (OPRs). Efforts to address the opioid crisis have focused mainly on reducing nonmedical OPR use. Too often overlooked, however, is the need for preventing and treating opioid addiction, which occurs in both medical and nonmedical OPR users. Overprescribing of OPRs has led to a sharp increase in the prevalence of opioid addiction, which in turn has been associated with a rise in overdose deaths and heroin use. A multifaceted public health approach that utilizes primary, secondary, and tertiary opioid addiction prevention strategies is required to effectively reduce opioid-related morbidity and mortality. We describe the scope of this public health crisis, its historical context, contributing factors, and lines of evidence indicating the role of addiction in exacerbating morbidity and mortality, and we provide a framework for interventions to address the epidemic of opioid addiction.