tbuckley/cabot-search huggingface dataset:
Skeletal Muscle–Specific Myosin Binding Protein-H Is Expressed in Purkinje Fibers of the Cardiac Conduction System
Authors: Tatiana Alyonycheva, Leona Cohen-Gould, Christiana Siewert, Donald A. Fischman, Takashi Mikawa
Journal: Circulation Research (1997)

Abstract Heart contraction is coordinated by conduction of electrical excitation through specialized tissues of the cardiac conduction system. By retroviral single-cell tagging and lineage analyses in the embryonic chicken heart, we have recently demonstrated that a subset of cardiac muscle cells terminally differentiates as cells of the peripheral conduction system (Purkinje fibers) and that this occurs invariably in perivascular regions of developing coronary arteries. Cis regulatory elements that function in transcriptional regulation of cells in the conducting system have been distinguished from those in contractile cardiac muscle cells; eg, 5′ regulatory sequences of the desmin gene act as enhancer elements in skeletal muscle and in the conduction system but not in cardiac muscle. We hypothesize that Purkinje fiber differentiation involves a switch of the gene expression program from that characteristic of cardiac muscle to one typical of skeletal muscle. To test this hypothesis, we examined the expression of myosin binding protein-H (MyBP-H) in Purkinje fibers of chicken hearts. This unique myosin binding protein is present in skeletal but not cardiac myocytes. A site-directed polyclonal antibody (AB105) was generated against MyBP-H. Immunohistological analysis of the myocardium mapped the AB105 antigen predominantly to A bands of myofibrils within Purkinje fibers. Western blot analysis of whole extracts from the ventricular wall of adult chicken hearts revealed that the AB105 epitope was restricted to a single protein of ≈86 kD, the same size as MyBP-H in skeletal muscle. Biochemical properties of the Purkinje fiber 86-kD protein and RNase protection analyses of its mRNA indicate that Purkinje fiber 86-kD protein is indistinguishable from skeletal muscle MyBP-H. The results provide evidence that skeletal muscle MyBP-H is expressed in a subset of cardiac muscle cells that differentiate into Purkinje fibers of the heart.
Anterior Cingulate Activity as a Predictor of Degree of Treatment Response in Major Depression: Evidence From Brain Electrical Tomography Analysis
Authors: Diego Pizzagalli, Roberto D. Pascual-Marqui, Jack B. Nitschke, Terrence R. Oakes, Christine L. Larson, Heather C. Abercrombie, Stacey M. Schaefer, John V. Koger, Ruth M. Benca, Richard J. Davidson
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The anterior cingulate cortex has been implicated in depression. Results are best interpreted by considering anatomic and cytoarchitectonic subdivisions. Evidence suggests depression is characterized by hypoactivity in the dorsal anterior cingulate, whereas hyperactivity in the rostral anterior cingulate is associated with good response to treatment. The authors tested the hypothesis that activity in the rostral anterior cingulate during the depressed state has prognostic value for the degree of eventual response to treatment. Whereas prior studies used hemodynamic imaging, this investigation used EEG. METHOD: The authors recorded 28-channel EEG data for 18 unmedicated patients with major depression and 18 matched comparison subjects. Clinical outcome was assessed after nortriptyline treatment. Of the 18 depressed patients, 16 were considered responders 4–6 months after initial assessment. A median split was used to classify response, and the pretreatment EEG data of patients showing better (N=9) and worse (N=9) responses were analyzed with low-resolution electromagnetic tomography, a new method to compute three-dimensional cortical current density for given EEG frequency bands according to a Talairach brain atlas. RESULTS: The patients with better responses showed hyperactivity (higher theta activity) in the rostral anterior cingulate (Brodmann's area 24/32). Follow-up analyses demonstrated the specificity of this finding, which was not confounded by age or pretreatment depression severity. CONCLUSIONS: These results, based on electrophysiological imaging, not only support hemodynamic findings implicating activation of the anterior cingulate as a predictor of response in depression, but they also suggest that differential activity in the rostral anterior cingulate is associated with gradations of response.
Lectures on the Diagnosis and Surgical Treatment of Abdominal Tumours
Authors: T. S. Wells
Journal: BMJ (1878)

GENTLEMEN,-The honourable position of Pro- fessor of Surgery and Pathology, which, by the kindness of my colleagues on the Council, I hold this year, has been filled in past times by some of the greatest men in our profession.Abernethy, Cooper, Bell, Green,
Notch signaling is an important regulator of type 2 immunity
Authors: LiLi Tu, Terry C. Fang, David Artis, Olga Shestova, Seth E. Pross, Ivan Maillard, Warren S. Pear
Journal: The Journal of Experimental Medicine (2005)

Notch ligands and receptors have been implicated in helper T cell (Th cell) differentiation. Whether Notch signals are involved in differentiation of T helper type 1 (Th1) cells, Th2 cells, or both, however, remains unresolved. To clarify the role of Notch in Th cell differentiation, we generated mice that conditionally inactivate Notch signaling in mature T cells. Mice that lack Notch signaling in CD4+ T cells fail to develop a protective Th2 cell response against the gastrointestinal helminth Trichuris muris. In contrast, they exhibit effective Th1 cell responses and are able to control Leishmania major infection. These data demonstrate that Notch signaling is a regulator of type 2 immunity.
Functional Idiotopes: Tumor Antigen–Directed Expression of CD8+ T-Cell Epitopes Nested in Unique NH2-terminal VH Sequence of Antiidiotypic Antibodies?
Authors: Kouichiro Kawano, Soldano Ferrone, Constantin G. Ioannides
Journal: Cancer Research (2005)

Abstract Antiidiotypic antibodies have been and are being used for cancer immunotherapy based on the rationale that Ab2 carrying an “internal image” of the corresponding tumor antigen can induce tumor antigen–specific antibodies (i.e., Ab3 and inhibit tumor growth). Recent evidence indicates that Ab2 also induces cellular responses by CD4+ and CD8+ T cells. This finding has raised the question of where the short peptides, which express CD8+ T-cell–defined epitopes, are located and their relationship with the tumor antigen. We found that two of the four known Ab2 associated with tumor antigen, with known amino acid sequence, express unique NH2-terminal VH sequences which precede the framework regions. Both the unique and the shared NH2-terminal VH sequences are nested MHC class I antigen–binding peptides. These peptides were highly homologous with peptides from corresponding tumor antigen (carcinoembryonic antigen, CD55, and human high molecular weight melanoma–associated antigen) but differed from the tumor antigen peptides by the presence of the side chain known to mediate stronger forces of interaction with other atoms. The presence of candidate CTL epitopes in NH2-terminal VH of Ab2 homologous with tumor antigen may be important for the development of novel immunotherapeutic strategies for cancer.
Effects of Transforming Growth Factor-β1 on Renal Extracellular Matrix Components and Their Regulating Proteins
Authors: JULIE A. DOUTHWAITE, TIMOTHY S. JOHNSON, JOHN L. HAYLOR, PHIL WATSON, A. MEGUID EL NAHAS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Transforming growth factor-β1 (TGF-β1) is widely regarded as a potent fibrogenic renal growth factor. In cell culture, TGF-β1 has been shown to increase various extracellular matrix (ECM) proteins and tissue inhibitors of metalloproteinases (TIMP), while decreasing matrix metalloproteinases (MMP), providing the optimum environment for progressive ECM accumulation. This study, which uses the isolated perfused rat kidney (IPRK), describes for the first time in a whole kidney preparation the action of TGF-β1 on factors associated with ECM processing. This model allows the study of the intact rat kidney with physiologic cell-cell interactions in the absence of confounding systemic influences. Left kidneys were removed from male Wistar rats by a nonischemic technique and perfused with a sterile, apyrogenic, endotoxin-free perfusate, based on the plasma volume expander Hemaccel (polygeline), at constant pressure in a recirculating IPRK system. Kidneys were perfused for 1 h either with (n = 3) or without (n = 3) recombinant human TGF-β1 (20 ng/ml). The effects of perfusion were controlled by comparison with the nonperfused contralateral kidney (n = 6). TGF-β1 was measured in the perfusate and urine, at the start and end of the experiment using an enzyme-linked immunosorbent assay to its biologically active form. After perfusion, sections of the kidneys were analyzed for changes in mRNA by Northern blotting. Significant increases in mRNA for fibronectin (7.5-fold, P < 0.01), heparan sulfate proteoglycan core protein (53-fold, P < 0.001), laminin β1 (12-fold, P < 0.001), collagen α1(IV) (17-fold, P < 0.001), collagen α1(III) (fourfold, P < 0.001), and MMP9 (twofold, P < 0.05) were observed after perfusion with TGF-β1. Measurement of TIMP1, TIMP2, TIMP3, MMP1, and MMP2 mRNA demonstrated no detectable change, whereas determination of mRNA for tissue transglutaminase, an enzyme capable of cross-linking many ECM components, showed an eightfold increase (P < 0.01). This study suggests that in the IPRK and in the absence of other exogenous growth factors, TGF-β1 selectively increases the synthesis of ECM and tissue transglutaminase without changes that would result in the reduction of ECM degradation.
Flibanserin for Treating Low Sexual Desire in Women
Authors: Jill Jin
Journal: JAMA (2015)

Flibanserin for Treating Low Sexual Desire in WomenLow sexual desire (libido) is a common type of sexual dysfunction in women and can be challenging to treat. Overview of Sexual Dysfunction in WomenSexual dysfunction can refer to difficulties in libido (sex drive), arousal, or orgasm.There are many causes of sexual dysfunction.Psychiatric conditions such as depression or anxiety or emotional distress from work or relationship stressors are common causes.Some medical conditions can also affect sexual function, such as heart disease, certain neurological conditions, arthritis, or hormone changes during menopause.Medications, especially antidepressants, can also cause sexual dysfunction.Addressing the underlying medical or psychological issues improves sexual function in most women.However, some women who have no other medical or psychological concerns still have low sexual desire that affects both their personal and relationship well-being.This condition is referred to as female sexual interest/arousal disorder.This is a new diagnosis in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition), which combined the previously separate disorders of hypoactive sexual desire disorder (HSDD) and female sexual arousal disorder.The prevalence of these disorders varies widely depending on the population surveyed, but studies have suggested it can range anywhere from 5% to 15% of women.Treatment of HSDD and female sexual arousal disorder can be challenging.
Antiphospholipid Syndrome in Systemic Lupus Erythematosus
Authors: Gary S. Hill, Dominique Nochy
Journal: Journal of the American Society of Nephrology (2007)

Renal biopsies occasionally show a combination of thrombotic microangiopathy as a result of antiphospholipid syndrome and lupus nephritis. The thrombosis in this case preceded the onset of lupus probably by approximately 8 yr, consisting of repeated fetal loss and venous thrombosis. More severe disease may have both arterial and venous thrombotic manifestations, including pulmonary emboli and cerebrovascular lesions. The antiphospholipid syndrome bears no relationship to the class of lupus nephritis but is accompanied by more frequent and greater hypertension and greater azotemia and interstitial fibrosis, and is associated with worse outcomes than lupus nephritis without antiphospholipid syndrome.
Human C-type natriuretic peptide: effects on the haemodynamic and endocrine responses to angiotensin II
Authors: R. I Cargill, A. D Struthers, B. J Lipworth
Journal: Cardiovascular Research (1995)

The aim was to study the effects of high dose systemic human C-type natriuretic peptide (CNP) infusion in man on systemic and pulmonary haemodynamics and the renin-angiotensin system before and after infusion of angiotensin II.Eight normal male volunteers were studied on two separate occasions when, after the subjects had been rested to reach a baseline haemodynamic state (T0), infusions of either human CNP (10 pmol.kg-1.min-1) or placebo (5% dextrose) were begun. After 30 min (T30) on each study day, a concomitant infusion of angiotensin II (6 ng.kg-1.min-1) was started, and both infusions ran together for a further 30 min (until T60). Measurements of systemic and pulmonary haemodynamic variables and the activity of the renin-angiotensin system were made at baseline (T0), after 30 min of CNP or placebo (T30), and after angiotensin II (T60).Infusion of CNP had no significant effects on systemic or pulmonary haemodynamics or on baseline renin-angiotensin system activity compared with placebo. Infusion of angiotensin II produced significant systemic and pulmonary pressor effects and also stimulated aldosterone secretion. There were, however, no significant differences between the changes induced by angiotensin II (expressed as the difference between T30 and T60) when CNP was infused compared with placebo: change in mean systemic arterial pressure with CNP 26.6(SEM 2.3) mm Hg v placebo 30.3(3.6) mm Hg; change in mean pulmonary artery pressure with CNP 11.7(2.5) mm Hg v placebo 10.9(1.0) mm Hg; change in aldosterone concentration with CNP 219(40) pmol.litre-1 v placebo 242(40) pmol.litre-1.At a dose of CNP which has previously been found to have marked haemodynamic effects in dogs, no effect on systemic or pulmonary haemodynamics was observed in man. Furthermore, CNP had no effect on the aldosterone or pressor responses to infused angiotensin II. The present study would suggest that CNP does not have a circulating endocrine role in cardiovascular homeostasis, although a paracrine role within vascular endothelium is perhaps more likely.
Changes in risk factors and Tumor Node Metastasis stage of sporadic medullary thyroid carcinoma over 41 years, before and after the routine measurements of serum calcitonin
Authors: Helen Karga, Irene Giagourta, Garyphallia Papaioannou, Konstantinos Doumouchtsis, Antonis Polymeris, Stavroula Thanou, Konstantinos Papamichael, Cherry Zerva
Journal: Metabolism (2010)
Analysis of factors regulating erythrocyte deformability.
Authors: N Mohandas, M R Clark, M S Jacobs, S B Shohet
Journal: Journal of Clinical Investigation (1980)

Using a laser diffraction technique, we have studied factors that influence the deformability of erythrocytes. Variations in suspending medium osmolality and applied shear stress were employed to isolate the individual contributions to whole cell deformability of internal viscosity, surface area-to-volume ratio, and viscoelastic properties of the membrane. An experimental system was devised in which normal cells were modified in vitro to induce specific alterations in each factor. Measurements of deformability as a function of medium osmolality showed characteristic behavior of the modified cells. Reduced surface area-to-volume ratio was detected by an exaggeration of the normal decrease in deformability as medium osmolality was decreased. In contrast, increased internal viscosity was detected by an increase in deformability as osmolality was decreased. Finally, decreased membrane flexibility was detected by reduced deformation at low shear stress. These methods of analysis were applied to cells from patients with hereditary spherocytosis, hereditary pyropoikilocytosis, and hemoglobin CC disease to define the basis of reduced deformability. Hereditary spherocytes showed the combined effects of reduced surface area and increased internal viscosity. Hereditary pyropoikilocytes revealed the effects of severely reduced surface area-to-volume ratio. Hemoglobin CC cells showed only the effects of high internal viscosity. An increase in the membrane shear modulus (decreased membrane deformability) was not evident in these disorders.
RISK OF INTERVERTEBRAL DISC DAMAGE AFTER PROLONGED SPACE FLIGHT
Authors: D Chang, JV Sayson, S Chiang, R Riascos-Castaneda, K Walker, JC Lotz, AR Hargens
Journal: British Journal of Sports Medicine (2014)

Background Back pain and intervertbral disc (IVD) damage are common problems experienced by astronauts. We hypothesize this is from paraspinal muscle deconditioning, ∼5 cm body lengthening from spinal swelling and straightening, and biochemical tissue changes. Objective Examine morphological changes in the lumbar spine induced by spaceflight. Design Prospective, case series clinical study. Setting We studied crewmembers from the National Aeronautics and Space Administration (NASA). Participants Recruitment from International Space Station NASA/European Space Agency/Canadian Space Agency crewmembers, starting 2011. We enrolled 8 NASA crewmembers. One crewmember completed the study. The others are in various stages of testing. Risk factors Assessment Crew members were studied before and after a ∼180 day mission in the International Space Station. Main outcome measurements In pre-flight and post-flight studies of the lumbar spine, evaluate: 1) degenerative changes using MRI, 2) compressibility using an upright MRI backpack loading protocol, 3) spinal kinematics with X-ray videography, 4) visual analog scale pain. Results Comparing pre-flight and post- flight data, there were 1) increased lumbar IVD heights in the supine position, 2) increased lumbar IVD compressibility in the upright position, 3) decreased flexibility, and 4) increased low back pain post-flight. Figure 1 Spinal kinematics (angles in degrees) during flexion/extension. Pre-flight degenerate disks had less motion. Post-flight, all disks had less motion. Conclusions The data support the idea that decreased gravitational forces on the IVDs, during prolonged microgravity, increases their water content but decreases proteoglycan. This increases disk degeneration risk on Earth. We have a sample size of one for complete Pre- and Post-Flight testing. It's difficult to make conclusions with this preliminary data. However, the acquired images are very high quality and provide confidence for future tests. The next crewmember returns to Earth for final testing November, 2013. Testing of 4 crewmembers and ongoing recruitment are underway.
Transmissible strains of<i>Pseudomonas aeruginosa</i>in cystic fibrosis lung infections
Authors: Joanne L. Fothergill, Martin J. Walshaw, Craig Winstanley
Journal: European Respiratory Journal (2012)

Pseudomonas aeruginosa chronic lung infections are the major cause of morbidity and mortality associated with cystic fibrosis. For many years, the consensus was that cystic fibrosis patients acquire P. aeruginosa from the environment, and hence harbour their own individual clones. However, in the past 15 yrs the emergence of transmissible strains, in some cases associated with greater morbidity and increased antimicrobial resistance, has changed the way that many clinics treat their patients. Here we provide a summary of reported transmissible strains in the UK, other parts of Europe, Australia and North America. In particular, we discuss the prevalence, epidemiology, unusual genotypic and phenotypic features, and virulence of the most intensively studied transmissible strain, the Liverpool epidemic strain. We also discuss the clinical impact of transmissible strains, in particular the diagnostic and infection control approaches adopted to counter their spread. Genomic analysis carried out so far has provided little evidence that transmissibility is due to shared genetic characteristics between different strains. Previous experiences with transmissible strains should help us to learn lessons for the future. In particular, there is a clear need for strain surveillance if emerging problem strains are to be detected before they are widely transmitted.
Effects of two weeks of topical budesonide treatment on microvascular exudative responsiveness in healthy human nasal airways
Authors: L Greiff, M Andersson, C Svensson, A Akerlund, U Alkner, CG Persson
Journal: European Respiratory Journal (1997)

Extravasation and luminal entry of plasma (mucosal exudation) is not only a key feature of airway inflammation in rhinitis and asthma but also a major first-line respiratory defence mechanism. Topical steroids are effective antiexudative agents in disease but, so far, little is known about the direct effects of these drugs on the responsiveness of the microcirculation in human airways. In this study, the effects of prolonged budesonide treatment on histamine-induced mucosal exudation of plasma was examined in 42 healthy subjects. Placebo and budesonide (100 microg per nasal cavity b.i.d.) were given for 2 weeks in a double-blind and placebo-controlled parallel-group protocol. Using a nasal pool technique, nasal challenges with isotonic saline and histamine (40 and 400 microg x mL(-1)) were carried out before and late in the treatment periods. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. Histamine produced concentration-dependent mucosal exudation of plasma before as well as after treatment with either placebo or budesonide. The topical steroid treatment only marginally (1.8 fold) decreased the response to the low concentration histamine (40 microg x mL(-1)) and, although it was significantly (2.8 fold) reduced, histamine 400 microg x mL(-1) still produced significant mucosal exudation of plasma in the budesonide group. If the present observations are extrapolated to inflammatory conditions, the antiexudative effects of topical steroids in rhinitis (and asthma) may reflect only a small degree of microvascular antipermeability effects. We suggest that topical steroid treatment may not impede mucosal exudation responses when called for in acute human airway defence reactions.
Dermoid cyst: a rare tumour of the appendix.
Authors: M H Cotton, J R Blake
Journal: Gut (1986)

Dermoid cyst is a rare but well recognised cause of a mass in the abdomen. As a cause of a palpable mass in the right iliac fossa, dermoid and epidermoid cysts of the caecum have hitherto been described. We here report a case of a dermoid cyst arising from the vermiform appendix.
PROSTATE WEIGHING SEVENTEEN OUNCES REMOVED BY THE SUPRAPUBIC ROUTE
Authors: A. Fullerton
Journal: BMJ (1909)

secondary symptoms, as it has often been noticed that parasyphilitic lesions have generally followed such cases, and it is rational to assume that in these instances the toxins which later on cause these lesions are produced early in the disease.Cases which do not take mercury well will be found to stand it much better if it be given in conjunction with iodipin.If the cases are being treated by injections of