tbuckley/cabot-search huggingface dataset:
Regional effects of verapamil on recovery of excitability and conduction time in experimental ischemia.
Authors: S Kimura, A L Bassett, T Kohya, P L Kozlovskis, R J Myerburg
Journal: Circulation (1987)

This study was designed to test the hypothesis that verapamil has an effect on ischemia-initiated arrhythmias related to its regional influences on recovery of excitability and conduction time. Using a coronary perfused preparation of cat left ventricle that allows simultaneous electrophysiologic monitoring of both endocardium and epicardium, we studied the effect of verapamil on ischemia-induced changes in transmembrane action potentials, conduction properties, and refractory periods of endocardial and epicardial muscle cells. Oxygenated Tyrode's solution was perfused through the left anterior descending coronary artery, while the preparation was superfused with Tyrode's solution gassed with 95% N2 and 5% CO2. "Ischemia" was produced by stopping coronary perfusion. During 30 min of ischemia, resting potential, action potential amplitude (APA), and action potential duration (APD) were reduced, and conduction time was prolonged in both endocardial and epicardial cells, but the changes were greater in the epicardial cells. Endocardial refractory periods shortened in parallel with APD shortening throughout 30 min of ischemia, whereas epicardial refractory periods shortened for the first 10 min and then increased due to development of longer postrepolarization refractoriness. As a result, there were significant differences in refractory periods between endocardial and epicardial cells at 10 and 30 min of ischemia, and rapid ventricular activity could be induced at these times. Exposure to verapamil (1 mg/liter) before cessation of coronary perfusion significantly limited the reduction of APA and the prolongation of conduction time during the first 10 min of ischemia in epicardial cells, but did not influence endocardial cells. During the remaining 20 min of ischemia, verapamil enhanced the reduction of APD of both epicardial and endocardial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Injuries to Knee Ligaments
Authors: James A. Nicholas
Journal: JAMA (1970)

With tests to determine the mobility of lower and upper extremities, 139 professional football players were classified as loose or tight, and subsequently checked for the incidence of major knee ligament rupture. Thirty-seven players sustained knee ligament rupture requiring surgery. Thirty-nine players had at least three indices of looseness. Twenty-eight (72%) of these ruptured their knee ligaments. Of the remaining 100 players with two or less indices, nine (9%) ruptured their ligaments. Only two (4%) players in the tight category (no indices of looseness) ruptured their ligaments. Increased likelihood of knee ligament rupture was found with increased looseness. Specific exercises should be designed to increase the strength of loose players and the mobility of tight players. By proper screening, it may be possible to reduce potential disabling knee ligament rupture in loose players in contact sports and in high velocity athletics.
TRANSILLUMINATION OF THE NASAL ACCESSORY SINUSES DURING ACUTE CORYZA.
Authors: CAROLUS M. COBB
Journal: JAMA (1903)

Transillumination of some of the accessory sinuses has been one of the stock tricks of traveling showmen for many years, and in every village where they exhibited a few of the more daring boys learned to make "fire come out of the eyes," and were a decided nuisance with it until something else took up their attention. That a lighted taper held in the closed mouth would, under proper conditions, illuminate the pupils of the eyes has probably been known for many years, but it was not known that the phenomenon was of any practical importance as a means of diagnosis until Voltolini of Breslau published the results of his experiments in 1888. In 1889 Heryng of Warsaw elaborated these experiments and placed transillumination on a practical working basis. Brown Kelly of Glasgow first called attention to the fact that the rays of light entered the eye and could
Fatal pneumococcal septicemia after splenectomy.
Authors: N. B. Karatzas
Journal: BMJ (1966)

phosphate is an essential precursor for the synthesis of trigly- cerides and can be synthesized only in adipose tissue, whereas the other precursors, fatty acids, probably originate in the liver as well as in adipose tissue (Bortz et al., 1962 ;Jacob, 1963).A slight reduction in activity of this enzyme (P=0.05)was found in adipose tissue of obese patients.However, the activity of the mitochondrial enzyme which oxidizes glycerol phosphate was found to be markedly reduced in adipose tissue of obese patients.This would be expected to increase the local supply of cytoplasmic glycerol phosphate if the supply from glycolysis remains unimpaired.Since the concentration of cytoplasmic glycerol phosphate is probably rate-limiting in the synthesis of triglycerides (Tzur et al., 1964), the physiological effects of its diminished oxidation by mitochondria might be a prolonged stimulation of lipogenesis.It is difficult to assess from the present studies the quantitative contribution that this might make to the development of obesity over the long term.It was not possible to show an increase in the pool of glycerol phosphate in adipose tissue of obese patients, and if the mito- chondrial defect described here is in fact leading to an increased availability of cytoplasmic glycerol phosphate the pool turnover must be increased.Hood and Bj6rntorp (1966) came to a similar conclusion, that the pool of cytoplasmic glycerol phos- phate in adipose tissue of obese patients was diluting the incor- poration of 14C-glycerol into lipid fivefold when compared with normal. SUMMARYAn enzymatic defect has been observed in adipose tissue of some obese patients which would be expected to increase the availability of a-glycerol phosphate for the synthesis of tri- glycerides.Two cases of obesity, with presumed lesions in the hypothalamus, did not display this defect to the same extent as their obese controls.The possibility is considered that extreme obesity of early onset is associated with an enzymatic defect in the metabolism of a-glycerol phosphate.
Influence of Breastfeeding on Obesity and Type 2 Diabetes Risk Factors in Latino Youth With a Family History of Type 2 Diabetes
Authors: Jaimie N. Davis, Marc J. Weigensberg, Gabriel Q. Shaibi, Noe C. Crespo, Louise A. Kelly, Christianne J. Lane, Michael I. Goran
Journal: Diabetes Care (2007)

To determine whether breastfeeding is related to total adiposity, regional adiposity, and glucose and insulin dynamics in overweight Latino youth throughout puberty.The relation between breastfeeding and diabetes risk was determined in 240 overweight (BMI > or =85th percentile) Latino children (aged 8-13 years) with a positive family history of type 2 diabetes. Children were examined at baseline (Tanner pubertal stage 1) and for 2 more years as they advanced in pubertal maturation. Children were divided into the following categories: never breastfed (n = 102), breastfed 0-5.99 months (n = 61), breastfed 6-11.99 months (n = 24), and breastfed > or =12 months (n = 53). Tanner pubertal stage was determined by physical examination. Visceral and subcutaneous abdominal fat were determined by magnetic resonance imagining, and total body fat, total lean tissue mass, and percent body fat were measured by dual-energy X-ray absorptiometry. Fasting and postchallenge glucose were assessed with a 2-h oral glucose tolerance test. Insulin sensitivity (SI), acute insulin response (AIR), and disposition index ([DI] an index of beta-cell function) were measured by frequently sampled intravenous glucose tolerance test and minimal modeling. Data were analyzed using linear mixed-effects modeling.There were no significant effects of breastfeeding categories on adiposity (i.e., total fat mass, total lean tissue mass, percent body fat), fat distribution (visceral and subcutaneous abdominal fat), fasting glucose or 2-h glucose, or insulin dynamics (SI, AIR, and DI) at Tanner pubertal stage 1 or on changes in these variables over pubertal transitions in overweight Latino youth.In this population of high-risk Latino youth, there were no significant protective effects of breastfeeding on adiposity or type 2 diabetes risk factors at Tanner pubertal stage 1 or across advances in maturation.
Decreased immunoregulatory activity of B cells derived from patients with systemic lupus erythematosus
Authors: Theresa Tretter, Nele Gao, Julia Dresel, Rimma Gellert, Hanns-Martin Lorenz
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Our group has recently generated human B cells with immunoregulatory properties in vitro from peripheral blood (PB) of healthy donors. Upon prestimulation via their B cell receptor (BCR) large, activated CD25+B cells (B25+), but not resting CD25−B-cells (B25−), induced temporary CD4+T cell energy and apoptosis. These results led us to rethink the so far pathogenic role of B cells in autoimmune disease. Our aim was to test the immunoregulatory capabilities of B-cells from patients with systemic lupus erythematosus (SLE), as an autoimmune disease with characteristic B cell involvement. Since Treg defects are reported, at least in advanced stages of disease, it could be suspected that Breg might be affected, as well. <h3>Materials and methods</h3> Highly purified CD19+B cells and CD4+Th-cells were separated from PBMC by magnetic cell sorting. B cells were prestimulated with SAC (<i>Staphylococcus aureus</i> Cowan I Antigen) for 3d and sorted into highly activated FSC<sup>hi</sup>CD25+ (B25+) and small resting FSC<sup>lo</sup>CD25- (B25-) B cells by cytometric cell sorting. Upon 4d coculture with Th-cells and αCD3+IL-2, T cell proliferation was determined by 3H-TdR incorporation. Experiments were set up in parallel with B cells from healthy donors (ND) and patients with SLE. For better comparison the study additionally included B cells from patients with another autoimmune disease, Wegener9s Granulomatosis (WG). <h3>Results</h3> CD4+T cell proliferation was significantly less inhibited in cocultures with SLE-B25+ compared to cocultures with ND-B25+ (mean 51% vs 35% of proliferation of T cells cultured alone (100%), p&lt;0.01). In cross-over-experiments ND-T cell proliferation decreased below 50% in 22 of 37 cases cocultured with SLE-B25+ but in 34 of 37 cases cocultured with ND-B25+. This effect was independent from T cell origin: SLE-T cell proliferation was similarly reduced below 50% in only 21 of 37 cases with SLE-B cells but in 32 of 37 cases with ND-B cells. Of interest, B25+ cells from patients with WG (n=37) exhibited strong inhibitory effects similar to their normal counterparts. So far, no differences in B cell activation markers, cytokine production or viability were found between ND-, WG- and SLE- B25+-cells. In addition no hints for a correlation between SLE-disease activity, treatment and Breg suppressor-function could be stated. <h3>Conclusions</h3> B25+ from SLE patients exhibit reduced regulatory capacity towards CD4+T cells in contrast to B25+ from healthy donors or patients with WG, suggesting that suppressive defects of SLE-B cells might be rather disease specific and less representative of autoimmunity in general or chronic inflammation. Future experiments deal with the SLE-B cell specificities interfering with suppressive function and the investigation for parameters to restore it.
LONG-TERM CLINICAL OUTCOMES OF TRUE AND NON-TRUE BIFURCATION LESIONS ACCORDING TO MEDINA CLASSIFICATION: RESULTS FROM THE COBIS (CORONARY BIFURCATION STENT) II REGISTRY
Authors: Taek Kyu Park, Young Bin Song, Yong Hwan Park, Ju Hyeon Oh, Woo Jin Jang, Jeong Hoon Yang, Joo-Yong Hahn, Seung-Hyuk Choi, Jin-Ho Choi, Sang Hoon Lee, Hyeon-Cheol Gwon
Journal: Journal of the American College of Cardiology (2014)
Thymosin β4 and its degradation product, Ac-SDKP, are novel reparative factors in renal fibrosis
Authors: Yiqin Zuo, Bongkwon Chun, Sebastian A. Potthoff, Naj Kazi, Tyler J. Brolin, Diclehan Orhan, Hai Chun Yang, Li Jun Ma, Valentina Kon, Timo Myöhänen, Nour Eddine Rhaleb, Oscar A. Carretero, Agnes B. Fogo
Journal: Kidney International (2013)
A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy
Authors: Anja Fritsch, Stefan Loeckermann, Johannes S. Kern, Attila Braun, Michael R. Bösl, Thorsten A. Bley, Hauke Schumann, Dominik von Elverfeldt, Dominik Paul, Miriam Erlacher, Dirk Berens von Rautenfeld, Ingrid Hausser, Reinhard Fässler, Leena Bruckner-Tuderman
Journal: Journal of Clinical Investigation (2008)

Dystrophic epidermolysis bullosa (DEB) is a severe skin fragility disorder associated with trauma-induced blistering, progressive soft tissue scarring, and increased risk of skin cancer. DEB is caused by mutations in type VII collagen. In this study, we describe the generation of a collagen VII hypomorphic mouse that serves as an immunocompetent animal model for DEB. These mice expressed collagen VII at about 10% of normal levels, and their phenotype closely resembled characteristics of severe human DEB, including mucocutaneous blistering, nail dystrophy, and mitten deformities of the extremities. The oral blistering experienced by these mice resulted in growth retardation, and repeated blistering led to excessive induction of tissue repair, causing TGF-beta1-mediated contractile fibrosis generated by myofibroblasts and pseudosyndactyly in the extremities. Intradermal injection of WT fibroblasts resulted in neodeposition of collagen VII and functional restoration of the dermal-epidermal junction. Treated areas were also resistant to induced frictional stress. In contrast, untreated areas of the same mouse showed dermal-epidermal separation following induced stress. These data demonstrate that fibroblast-based treatment can be used to treat DEB in a mouse model and suggest that this approach may be effective in the development of clinical therapeutic regimens for patients with DEB.
EC gives options for reducing smoking in Europe
Authors: Rory Watson
Journal: BMJ (2007)

The European Commission has stepped up its campaign against tobacco by issuing a consultative green paper that gives possible ways to promote smoke-free environments throughout Europe. 

The options range from doing nothing, through voluntary measures, to binding legislation. Markos Kyprianou, the European Union health commissioner and author of the initiative, has made clear his personal preference. 

“I would like to see a comprehensive complete ban operating everywhere in Europe. This would bring the biggest benefits to society as a whole. It would be easier to enforce and control and would put everyone …
Relevance of the determination of serum‐specific IgE antibodies in the diagnosis of immediate <i>β</i>‐lactam allergy
Authors: C. Fontaine, C. Mayorga, P. J. Bousquet, B. Arnoux, M.‐J. Torres, M. Blanca, P. Demoly
Journal: Allergy (2006)

Background: Allergic reactions to β ‐lactams are the most frequent cause of adverse drug reactions mediated by specific immunologic mechanisms. They can be explored by in vivo and/or in vitro tests. The measurement of serum‐specific immunoglobulin E (IgE) presents several advantages: safety, simplicity, and availability to nonallergologist physicians. Objectives: To establish the diagnostic value of specific IgE determination in the diagnosis procedure of immediate β ‐lactam allergy. Methods: The in vitro determination of β ‐lactam‐specific IgE antibodies was compared in three well‐defined groups of patients ( n = 45): one with negative skin tests and a positive drug provocation test, another with positive skin tests, and a third control exposed population with good tolerance. Two techniques were used: the CAP‐FEIA system (Phadia ® ) commercially available and a homemade radioallergosorbent test (RAST). Results: The specificity of CAP‐FEIA ranged from 83.3% to 100% and sensitivity from 0% to 25% depending on initial clinical manifestations. The specificity of RAST was between 66.7% and 83.3% and sensitivity 42.9% and 75%. In the subgroup of patients with an anaphylactic shock and negative skin tests, the sensitivity and specificity of RAST were 75%. Positive and negative predictive values were 45.5% and 77.1% with CAP‐FEIA and 38.5% and 81.5% with RAST, respectively. Conclusion: These results indicate that, although the specificity of β ‐lactam‐specific IgE measurement is good, sensitivity is low. Immunoglobulin E measurement should be limited to patients with a clinical history of anaphylactic shock and negative skin tests in order to avoid a drug provocation test. More sensitive assays should be developed.
A TREK-1–Like Potassium Channel in Atrial Cells Inhibited by β-Adrenergic Stimulation and Activated by Volatile Anesthetics
Authors: Cécile Terrenoire, Inger Lauritzen, Florian Lesage, Georges Romey, Michel Lazdunski
Journal: Circulation Research (2001)

Many members of the two-pore-domain potassium (K + ) channel family have been detected in the mammalian heart but the endogenous correlates of these channels still have to be identified. We investigated whether I KAA , a background K + current activated by negative pressure (stretch) and by arachidonic acid (AA) and sensitive to intracellular acidification, could be the native correlate of TREK-1 in adult rat atrial cells. Using the inside-out configuration of the patch-clamp technique, we found that I KAA , like TREK-1, was outwardly rectifying in physiological K + conditions, with a conductance of 41 pS at +50 mV. Like TREK-1, I KAA was reversibly activated by clinical concentrations of volatile anesthetics (in mmol/L, chloroform 0.18, halothane 0.11, and isoflurane 0.69). In cell-attached experiments, I KAA was inhibited by chlorophenylthio-cAMP (500 μmol/L) and also by stimulation of β-adrenergic receptors with isoproterenol (1 μmol/L). In addition, TREK-1 mRNAs were detected in all cardiac tissues, and the TREK-1 protein was immunolocalized in isolated atrial myocytes. Such a background potassium channel might contribute to the positive inotropic effects produced by β-adrenergic stimulation of the heart. It might also be involved in the regulation of the atrial natriuretic peptide secretion.
Breaking the Cigarette Habit
Authors: Starr Ford
Journal: JAMA (1965)

Many methods have been used to assist the individual to discontinue cigarette smoking. A limited measure of success has been obtained by means of educational campaigns, psychotherapy, or pharmacological aids. Combinations of these therapeutic methods in smoking treatment clinics have produced only temporary alteration of cigarette-smoking habits. Review of the accumulated experience to date suggests that further development of methods for terminating the cigarette habit should include emphasis on the psychological and social factors which perpetuate the habit, reinforcement of the habit of "not smoking" for at least two years, and elevation of smoking treatments on the basis of long-term results.
Delays in cleft palate detection are "unacceptable," says royal college
Authors: Z. Kmietowicz
Journal: BMJ (2014)

<h3>Abstract</h3> Keshan disease (KD), an endemic heart disease with multifocal necrosis and replacement fibrosis of the myocardium,is still a nightmare situation for human health. However, molecular mechanism in the pathogenesis of KD remains unclear. Herein, blood samples were collected from 68 KD patients and 100 controls, and we systematically analyzed mutation profiles using whole-exome sequencing (WES). Causative genes of dilated cardiomyopathy (DCM), gene-based burden analysis, disease and pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed. Of the 98 DCM-causative genes, 106 rare variants in 28 genes were detected in KD patients with minor allele frequency (MAF) &lt; 0.001. Gene-based burden analysis, PPI network analysis, and automated Phenolyzer analysis were performed to prioritize 199 candidate genes, which combined with 98 DCM-causative genes, and reference genes from gene microarray or proteomics in KD. Then, 19 candidate pathogenic genes were selected, and 9 candidate genes were identified using PPI analysis, including <i>HIF1A, GART, ALAD, VCL, DTNA, NEXN, INPPL1, NOS3</i>, and <i>JAK2</i>. The 199 candidate genes were further analyzed using disease enrichment with CTD database and PPI analysis, and 21 candidate genes were identified. By combining with disease enrichment and PPI analysis, 7 Selenium (Se)-related genes were further identified, including <i>ALAD, RBM10, GSN, GGT1, ADD1, PARP1</i>, and <i>NOS3</i>. Based on the gene function and data validation, <i>NEXN, TAF1C, FUT4, ALAD, ZNF608</i>, and <i>STX2</i> were the most likely pathogenic genes in KD. Notably, <i>ALAD</i> is the only candidate pathogenic gene identified by four different analyses, and its homozygous mutant mice could affect heart development and cause death.
THE ACIDOSIS OF GUANIDINE INTOXICATION 1
Authors: A. S. Minot, Katharine Dodd, J. M. Saunders
Journal: Journal of Clinical Investigation (1934)

Recent reports (1) (2) (3) (4) (5) which implicate guanidine intoxi- cation as a complicating factor in some instances of acute liver injury, of eclampsia, and of alimentary intoxication in infants, make it desirable to know in greater detail the effect of guanidine on various biological proc- esses.Only in this way can we know in what manner increased guanidine may modify the clinical picture in a given disease and may influence the response of the patient to treatment of his symptoms.Since acidosis must often be treated in the presence of hyperguanidinemia, it is of interest to study the effect of guanidine intoxication on the acid base equilibrium.Various observers have mentioned breathing of the " air hunger " type in guanidine poisoning.Watanabe (6) reported a decrease in pH and CO2 of the blood and an increased output of ammonia in the urine of ex- perimental animals poisoned with guanidine.His results were disputed by Gy6rgy and Vollmer (7) who argued that a condition of alkalosis rather than acidosis must be produced since the hyperirritability caused by guani- dine can be relieved by the administration of acid.These authors, how- ever, presented no studies of acid base equilibrium to substantiate their claims.We already have considerable evidence that one feature of the intoxication is a serious disturbance of lactic acid metabolism.In an in- vestigation of the hypoglycemia induced by guanidine and by its derivative synthalin, Staub (8) showed that lactic acid accumulates in the tissues and body fluids and is excreted in the urine.He attributes this accumulation to the inability of tissues poisoned with guanidine to oxidize and resynthe- size lactic acid to its precursors in a normal manner.Gradually more and more of the carbohydrate reserve is transformed to lactic acid until a severe hypoglycemia results.Minot (9) confirmed these observations both in experimental guanidine poisoning and in the intoxication which occurs when hyperguanidinemia is a result of acute extensive necrosis of the liver.Although no acid base studies were reported in connection with either of these investigations one would expect that, as lactic acid accumulates and is neutralized, there would be a progressive depletion of the alkali reserve.