tbuckley/cabot-search huggingface dataset:
The first heart sound in left bundle branch block: an echophonocardiographic study.
Authors: G W Burggraf
Journal: Circulation (1981)

To examine the nature of the first heart sound in left bundle branch block (LBBB), 26 patients with LBBB were studied using echophonocardiography. Apexcardiograms and systolic time intervals were also obtained from these patients and the results were compared with 20 normal subjects. Mitral closure preceded tricuspid closure by 0.02-0.04 second in 19 of the 20 normal subjects. In contrast, in subjects with LBBB there was a variable delay in mitral closure so that in seven subjects the sequence of mitral and tricuspid closure was normal, in 11 it was reversed compared wih the normal group, and in eight closure of both valves was simultaneous. The interval from the onset of ventricular depolarization to mitral closure was 0.074 +/- 0.019 (mean +/- SD) for the patients with LBBB and 0.057 +/- 0.008 second for the normal group (p &lt; 0.001). With LBBB the first sound tended to be of reduced intensity and separate mitral and tricuspid components could not be identified. Systolic time intervals and the apexcardiograms demonstrated a delayed onset of left ventricular contraction and an increased isometric contraction time in the LBBB group, both of which would contribute to a delayed mitral valve closure and decreased first heart sound intensity.
MENTAL CHANGES IN CHOREA MINOR
Authors: Donald Shaskan
Journal: American Journal of Psychiatry (1938)

1. Chorea minor was studied with special interest in its mental manifestations. Granted that we are dealing with the same fundamental syndrome, nevertheless for convenience in diagnosis and prognosis it was found helpful to classify our cases in 3 groups: I. Chorea with severe psychosis; II. Chorea with mild mental disturbance; III. Chorea without gross mental changes. 2. The mental changes in chorea are closely connected with disturbances in impulse. Emotional instability such as increased laughing and crying predominate. In the milder and uncomplicated cases there are no serious disturbances in thinking or in orientation; although behavior disturbances may offer a serious problem. In the severe cases, the hyperkinesis and akinesis influence thinking. Hallucinations and delusions often are present. In the more severe cases confusion and disorientation may supervene. 3. The motility disturbances of chorea and schizophrenia are occasionally similar but their respective mental pictures are distinct. 4. In these patients with severe mental symptoms atypical motor signs such as flaccidity, tonic and rhythmical phenomena were observed. 5. Severe mental symptoms were a grave prognostic sign and seen particularly in older patients. 6. Fever therapy did not prove beneficial in chorea with severe psychosis but was helpful in patients with minor mental symptoms and advantageous in the treatment of behavior problems associated with chorea. I am indebted to Drs. Karl M. Bowman and Charles Hendee Smith, Directors, respectively, of the Psychiatric and Pediatric Divisions, Bellevue Hospital, for permission to use the clinical material presented and to Dr. Douglas Symmers, Director of Laboratories of New York City, for permission to use a pathological report. I wish to thank Drs. Paul Schilder, Normal Jolliffe, Lewis D. Stevenson and Lauretta Bender for their aid.
Side-effects of azathioprine treatment in rheumatoid arthritis: analysis of 10 years of experience.
Authors: F Speerstra, A M Boerbooms, L B van de Putte, H J van Beusekom, M W Kruijsen, J P Vandenbroucke
Journal: Annals of the Rheumatic Diseases (1982)

Our experience with azathioprine in the treatment of rheumatoid arthritis covers ten years, during which 91 rheumatoid patients (66 female and 25 male) received this drug, with a median treatment period of 36 months. Total follow-up experience, during and after treatment, was 399 person years. Twelve patients died. The principal causes of death were malignant neoplasm (six patients) and cardiovascular diseases (three patients). The mortality in our patients was compared to that of the general Dutch population by the Standardised Mortality Ratio (SMR). In the male patient group a significant excess of both total mortality and mortality from malignancy was observed. The female patients showed no differences from the general population. In this follow-up study, no lymphoreticular tumours occurred during or after azathioprine therapy.
THE TREATMENT OF PERFORATED GASTRIC AND DUODENAL ULCERS: With a Report on Forty Consecutive Cases
Authors: G. P. Mills
Journal: BMJ (1925)

THis paper is a plea for the p)erformance of gastAro- *jejunostomy whenever possible at the timie of op)erlatioll for r)erfoeation.Beginninig witih some apprehension, I liave beeni led to do so more anid moic frequently withi inicreasing eIxperlience, an(d L niow regard it as almo.st a rouitine part of the operationi.The cases anialyvsed below are all those I liave treated in hosp)ital since' my retulrn from-l the war: 16 were duodenal, 15 pre-pyloric, 5 in the body of the stomiiach, and( in 4 the situLatioin of tile ulcer is not stated ill the niotes.Tlhere were 38 males anid 2 females.T-eatinent.Every case but one was operated oni.This patienlt w-as mnoribuind on admission, and failed to rally withl treatment.The deatlh is included in the mortality statistics.Ill early cases, seeni wvithin abouit twelve hiours of perforationi, sutuire of the ulcer anid gastro-jejunostomy was performed witlhout drainage of the periitoneum, excel)t in thiree inistances of
CREB-independent regulation by CBP is a novel mechanism of human growth hormone gene expression
Authors: Laurie E. Cohen, Yukiko Hashimoto, Kerstin Zanger, Fredric Wondisford, Sally Radovick
Journal: Journal of Clinical Investigation (1999)

Hypothalamic growth hormone–releasing hormone (GHRH) stimulates growth hormone (GH) gene expression in anterior pituitary somatotrophs by binding to the GHRH receptor, a G-protein–coupled transmembrane receptor, and by mediating a cAMP-mediated protein kinase A (PKA) signal-transduction pathway. Two nonclassical cAMP-response element motifs (CGTCA) are located at nucleotides –187/–183 (distal cAMP-response element; dCRE) and –99/–95 (proximal cAMP-response element; pCRE) of the human GH promoter and are required for cAMP responsiveness, along with the pituitary-specific transcription factor Pit-1 (official nomenclature, POU1F1). Although a role for cAMP-response element binding protein (CREB) in GH stimulation by PKA has been suggested, it is unclear how the effect may be mediated. CREB binding protein (CBP) is a nuclear cofactor named for its ability to bind CREB. However, CBP also binds other nuclear proteins. We determined that CBP interacts with Pit-1 and is a cofactor for Pit-1–dependent activation of the human GH promoter. This pathway appears to be independent of CREB, with CPB being the likely target of phosphorylation by PKA.
Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles
Authors: Sheila Seal, Deborah Thompson, Anthony Renwick, Anna Elliott, Patrick Kelly, Rita Barfoot, Tasnim Chagtai, Hiran Jayatilake, Munaza Ahmed, Katarina Spanova, Bernard North, Lesley McGuffog, D Gareth Evans, Diana Eccles, Douglas F Easton, Michael R Stratton, Nazneen Rahman
Journal: Nature Genetics (2006)
Risk of Bleeding after Elective Percutaneous Coronary Intervention
Authors: William W. O'Neill
Journal: New England Journal of Medicine (2006)

About 2.2 million percutaneous coronary interventions (PCIs) were performed worldwide in 2004 (Mead D: personal communication). Success rates of more than 97%, mortality rates of less than 0.5%, and rates of emergency bypass surgery of less than 0.5% can be anticipated with elective procedures. Major obstacles initially confronting the field — including the inability to reach complex or tortuous lesions, to cross lesions, and to dilate lesions, as well as bifurcation disease, occlusive dissection, and abrupt closure — have largely been overcome. Restenosis has been markedly reduced with the advent of drug-eluting stents.1 As the technical obstacles to safe, effective, . . .
Epstein-Barr Virus Latent Membrane Protein-1 Effects on Junctional Plakoglobin and Induction of a Cadherin Switch
Authors: Kathy H.Y Shair, Caroline I. Schnegg, Nancy Raab-Traub
Journal: Cancer Research (2009)

Latent membrane protein-1 (LMP1) is considered the major oncoprotein of Epstein-Barr virus and is frequently expressed in nasopharyngeal carcinoma (NPC). LMP1 promotes growth and migration of epithelial cells, and the loss of plakoglobin has been identified as a contributing factor to LMP1-induced migration. Plakoglobin is a junctional protein that can also serve as a transcription factor in Tcf/Lef signaling. To determine the effects of LMP1 on the molecular and functional properties of plakoglobin, LMP1 was overexpressed in the NPC cell line C666-1. LMP1 did not affect plakoglobin stability but did decrease plakoglobin transcription. The resultant decreased levels of nuclear plakoglobin did not affect Tcf/Lef activity or the amount of plakoglobin bound to Tcf4. Although LMP1 induced and stabilized beta-catenin, a protein with common binding partners to plakoglobin, the loss of plakoglobin did not affect its association with Tcf4. However, LMP1 did induce a cadherin switch from E- to N-cadherin, a process involved in cancer progression, and enhanced the association of junctional beta-catenin with N-cadherin. LMP1 decreased overall levels of junctional plakoglobin but the remaining junctional plakoglobin was found associated with the induced N-cadherin. This increased association of junctional plakoglobin with N-cadherin was a distinguishing feature of LMP1-expressing cells that have reduced migration due to restoration of plakoglobin. Low levels of plakoglobin were also detected in human NPC tissues. These findings reveal that the effects of LMP1 on junctional plakoglobin and the initiation of a cadherin switch likely contribute to metastasis of NPC.
THE DEGREE OF COMPENSATORY RENAL HYPERTROPHY FOLLOWING UNILATERAL NEPHRECTOMY
Authors: E. M. MacKay, L. L. MacKay, T. Addis
Journal: The Journal of Experimental Medicine (1932)

Compensatory hypertrophy of the kidney in albino rats becomes less as age advances. There is a rapid decrease from 5 days to 60 days of age and then a slow diminution throughout adult life.
Airway endothelin levels in asthma: influence of endobronchial allergen challenge and maintenance corticosteroid therapy
Authors: AE Redington, DR Springall, MA Ghatei, J Madden, SR Bloom, AJ Frew, JM Polak, ST Holgate, PH Howarth
Journal: European Respiratory Journal (1997)

Endothelins (ETs) are 21 amino acid peptides which, in addition to their other properties, are potent bronchoconstrictors. Whilst there is evidence of the involvement of ET in the pathophysiology of chronic asthma, its contribution to the acute allergic response is undefined. To examine this, we have undertaken segmental bronchoprovocation with allergen and saline at separate sites in six atopic asthmatics receiving treatment with bronchodilators only and six atopic asthmatics additionally receiving treatment with inhaled corticosteroids. Each challenged segment was lavaged 10 min after bronchoprovocation and concentrations of immunoreactive ET were measured in bronchoalveolar lavage fluid. In the non-steroid-treated subjects, there were significantly lower ET levels at the allergen-challenged sites compared to the saline-challenged sites (p&lt;0.05). In the steroid-treated subjects, on the other hand, there was no significant difference between the two sites. Levels of ET at the saline-challenged sites were significantly lower in the steroid-treated subjects compared to the non-steroid-treated subjects (p&lt;0.04). These findings do not support the hypothesis that allergen exposure in asthma results in immediate release of endothelin. However, release at later time-points and a role for endothelin in late-phase bronchoconstriction are not excluded.
Immune Responses in MHC Class II-Deficient MICE
Authors: M J Grusby, L H Glimcher
Journal: Annual Review of Immunology (1995)

Major histocompatibility complex (MHC) class II molecules are heterodimeric cell surface proteins that are critically important for the development and function of cells in the immune system. In particular, the maturation of CD4+ T cells is dependent on the expression of MHC class II molecules on thymic epithelium, while the activation of these cells requires the expression of class II molecules on specialized antigen-presenting cells in the periphery. The importance of class II molecules is especially evident in humans who are afflicted with MHC class II-deficient combined immunodeficiency, as these individuals die at an early age unless provided with a bone marrow transplant. Here we discuss the functional consequences of MHC class II deficiency in a mouse model generated by gene targeting in embryonic stem (ES) cells. These mice have proved to be valuable reagents for dissecting the mechanisms by which MHC class II molecules control the maturation and activation of lymphocytes as well as for elucidating the role of these cells in various immune responses.
B cell exchange across the blood-brain barrier in multiple sclerosis
Authors: H.-Christian von Büdingen, Tracy C. Kuo, Marina Sirota, Christopher J. van Belle, Leonard Apeltsin, Jacob Glanville, Bruce A. Cree, Pierre-Antoine Gourraud, Amy Schwartzburg, Gabriella Huerta, Dilduz Telman, Purnima D. Sundar, Tyler Casey, David R. Cox, Stephen L. Hauser
Journal: Journal of Clinical Investigation (2012)

In multiple sclerosis (MS) pathogenic B cells likely act on both sides of the blood-brain barrier (BBB). However, it is unclear whether antigen-experienced B cells are shared between the CNS and the peripheral blood (PB) compartments. We applied deep repertoire sequencing of IgG heavy chain variable region genes (IgG-VH) in paired cerebrospinal fluid and PB samples from patients with MS and other neurological diseases to identify related B cells that are common to both compartments. For the first time to our knowledge, we found that a restricted pool of clonally related B cells participated in robust bidirectional exchange across the BBB. Some clusters of related IgG-VH appeared to have undergone active diversification primarily in the CNS, while others have undergone active diversification in the periphery or in both compartments in parallel. B cells are strong candidates for autoimmune effector cells in MS, and these findings suggest that CNS-directed autoimmunity may be triggered and supported on both sides of the BBB. These data also provide a powerful approach to identify and monitor B cells in the PB that correspond to clonally amplified populations in the CNS in MS and other inflammatory states.
Biphasic Constrictor Response of the Rabbit Ear Artery
Authors: JOHN A. BEVAN, JOHN G. WATERSON
Journal: Circulation Research (1971)

The perfused rabbit ear artery shows a biphasic contractile response to intraluminal norepinephrine and sympathetic nerve stimulation. The peak of the first phase occurs after approximately 10 seconds of exposure to NE, and the second, after 1½ to 2 minutes. The magnitudes of the two responses are similar. The time course of the second phase of contraction is similar to the rate of saturation of the vessel's extracellular space as measured by tissue uptake of tritiated norepinephrine. On the other hand, the first phase of contraction occurs when norepinephrine has penetrated only partly into the media. It is proposed that the two phases of contraction are due to different mechanisms of excitation and that the first phase is associated with excitation of the surface layer of smooth muscle cells with subsequent myogenic propagation of excitation through the thickness of the vessel wall. The second may be related to the local concentration of norepinephrine in the extracellular space of the vessel.
Short Communication: Vascular Smooth Muscle Cell Stiffness As a Mechanism for Increased Aortic Stiffness With Aging
Authors: Hongyu Qiu, Yi Zhu, Zhe Sun, Jerome P. Trzeciakowski, Meredith Gansner, Christophe Depre, Ranillo R.G. Resuello, Filipinas F. Natividad, William C. Hunter, Guy M. Genin, Elliot L. Elson, Dorothy E. Vatner, Gerald A. Meininger, Stephen F. Vatner
Journal: Circulation Research (2010)

Increased aortic stiffness, an important feature of many vascular diseases, eg, aging, hypertension, atherosclerosis, and aortic aneurysms, is assumed because of changes in extracellular matrix (ECM).We tested the hypothesis that the mechanisms also involve intrinsic stiffening of vascular smooth muscle cells (VSMCs).Stiffness was measured in vitro both by atomic force microscopy (AFM) and in a reconstituted tissue model, using VSMCs from aorta of young versus old male monkeys (Macaca fascicularis) (n=7/group), where aortic stiffness increases by 200% in vivo. The apparent elastic modulus was increased (P<0.05) in old (41.7+/-0.5 kPa) versus young (12.8+/-0.3 kPa) VSMCs but not after disassembly of the actin cytoskeleton with cytochalasin D. Stiffness of the VSMCs in the reconstituted tissue model was also higher (P<0.05) in old (23.3+/-3.0 kPa) than in young (13.7+/-2.4 kPa).These data support the novel concept, not appreciated previously, that increased vascular stiffness with aging is attributable not only to changes in ECM but also to intrinsic changes in VSMCs.
Ara H 9 Is The Main Allergen In Peanut Allergic Patients In The Mediterranean Area Regardless The Symptom Severity
Authors: M. Ferrer, G. Javaloyes, I. García Nuñez, G. Gastaminza, M. Goikoetxea, C. Gamazo, J. Souza, B. Sastre, V. del Pozo, M. Blanca, S. Vieths, S. Scheurer, M.L. Sanz
Journal: Journal of Allergy and Clinical Immunology (2011)
Statistical Analysis of DNA Sequences
Authors: B. S. Weir
Journal: JNCI Journal of the National Cancer Institute (1988)

Developments in the statistical analysis of DNA sequence data since 1984 are reviewed. Mathematical methods employing dynamic programming or incorporating Markov chain theory have been developed to search sequences for regions of similarity and to align sequences. When the biological forces of mutation and genetic drift are included in models, distances between aligned sequences allow the construction of evolutionary trees. Theory based on models may lead to estimates of variation of parameter estimates and so give a means of assessing the statistical significance of observed patterns and relationships. The complexity of DNA sequences, however, suggests that most statistical inferences will rest on random permutations of sequences. [J Natl Cancer Inst 1988;80:395–406]
Plakophilin-2 Mutations Are the Major Determinant of Familial Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: J.Peter van Tintelen, Mark M. Entius, Zahurul A. Bhuiyan, Roselie Jongbloed, Ans C.P. Wiesfeld, Arthur A.M. Wilde, Jasper van der Smagt, Ludolf G. Boven, Marcel M.A.M. Mannens, Irene M. van Langen, Robert M.W. Hofstra, Luuk C. Otterspoor, Pieter A.F.M. Doevendans, Luz-Maria Rodriguez, Isabelle C. van Gelder, Richard N.W. Hauer
Journal: Circulation (2006)

Background— Mutations in the plakophilin-2 gene ( PKP2 ) have been found in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC). Hence, genetic screening can potentially be a valuable tool in the diagnostic workup of patients with ARVC. Methods and Results— To establish the prevalence and character of PKP2 mutations and to study potential differences in the associated phenotype, we evaluated 96 index patients, including 56 who fulfilled the published task force criteria. In addition, 114 family members from 34 of these 56 ARVC index patients were phenotyped. In 24 of these 56 ARVC patients (43%), 14 different (11 novel) PKP2 mutations were identified. Four different mutations were found more than once; haplotype analyses revealed identical haplotypes in the different mutation carriers, suggesting founder mutations. No specific genotype-phenotype correlations could be identified, except that negative T waves in V 2 and V 3 occurred more often in PKP2 mutation carriers ( P &lt;0.05). Of the 34 index patients whose family members were phenotyped, 23 familial cases were identified. PKP2 mutations were identified in 16 of these 23 ARVC index patients (70%) with familial ARVC. On the other hand, no PKP2 mutations at all were found in 11 probands without additional affected family members ( P &lt;0.001). Conclusions— PKP2 mutations can be identified in nearly half of the Dutch patients fulfilling the ARVC criteria. In familial ARVC, even the vast majority (70%) is caused by PKP2 mutations. However, nonfamilial ARVC is not related to PKP2 . The high yield of mutational analysis in familial ARVC is unique in inherited cardiomyopathies.
EXPERIMENTAL TRANSMISSION OF INFLUENZA VIRUS INFECTION IN MICE
Authors: Jerome L. Schulman, Edwin D. Kilbourne
Journal: The Journal of Experimental Medicine (1963)

Evidence has been presented that with the experimental model described, infected mice vary in their ability to transmit influenza virus infection. This variation is not explained by differences in titers of influenza virus in the nose, throat, trachea, or lungs of good transmitters. Older mice acquire transmitted influenza virus infection more readily than younger mice. Seasonal variations in the incidence of transmitted influenza virus infection occur.
Clinical Characteristics of Children Diagnosed With Type 1 Diabetes Through Intensive Screening and Follow-Up
Authors: Jennifer M. Barker, Stephanie H. Goehrig, Katherine Barriga, Michelle Hoffman, Robert Slover, George S. Eisenbarth, Jill M. Norris, Georgeanna J. Klingensmith, Marian Rewers
Journal: Diabetes Care (2004)

OBJECTIVE—The objective of this study was to determine whether earlier diagnosis of diabetes in prospectively followed autoantibody-positive children lowered onset morbidity and improved the clinical course after diagnosis. RESEARCH DESIGN AND METHODS—The Diabetes Autoimmunity Study in the Young (DAISY) follows genetically at-risk children for the development of diabetes. Increased genetic risk is identified by family history of type 1 diabetes or expression of diabetes-associated HLA genotypes. Of the 2,140 prospectively followed children, 112 have developed islet autoantibodies and 30 have progressed to diabetes. Diabetes onset characteristics and early clinical course of these 30 children followed to diabetes were compared with those of 101 age- and sex-matched children concurrently diagnosed with diabetes in the community. RESULTS—Pre-diabetic children followed to diabetes were less often hospitalized than the community cases (3.3 vs. 44%; P &amp;lt; 0.0001). They had a lower mean HbA1c at onset (7.2 vs. 10.9%; P &amp;lt; 0.0001) and 1 month after diagnosis (6.9 vs. 8.6%; P &amp;lt; 0.0001) but not after 6 months of diabetes. The mean insulin dose was lower in the DAISY group at 1 (0.30 vs. 0.51 U · kg−1 · day−1; P = 0.003), 6 (0.37 vs. 0.58; P = 0.001), and 12 months (0.57 vs. 0.72; P = 0.03). There was no difference in growth parameters between the two groups. Comparisons limited to children with a family history of type 1 diabetes in both groups showed a similar pattern. CONCLUSIONS—Childhood type 1 diabetes diagnosed through a screening and follow-up program has a less severe onset and a milder clinical course in the first year after diagnosis.