tbuckley/cabot-search huggingface dataset:
A role for depolarisation induced calcium entry on the Na-Ca exchange in triggering intracellular calcium release and contraction in rat ventricular myocytes
Authors: A. J Levi, P. Brooksby, J. C Hancox
Journal: Cardiovascular Research (1993)

Objective: The aim was to test whether depolarisation-induced calcium entry on the Na-Ca exchange is able to trigger calcium release from the sarcoplasmic reticulum in rat ventricular myocytes. Methods: Myocytes were isolated enzymatically from the left ventricle of the rat heart. Cells were impaled with narrow tipped microelectrodes to minimise intracellular dialysis and maintain normal internal ionic conditions. Cells were voltage clamped, contraction was measured optically, and in some experiments intracellular calcium was measured with Fura-2. Results: When the fast Na current was inactivated by using a holding potential of −40 mV, Ca entry via L-type Ca channels was expected to be the only mechanism capable of triggering sarcoplasmic reticular Ca release. In this situation, blocking L-type Ca channels should have abolished sarcoplasmic reticular release and the phasic twitch. However, after 2 min exposure to 20 μM nifedipine, which abolished the Ca current (ICa) completely, voltage clamp depolarisation from −40 mV to 0 mV still elicited 41(SEM 8.9)% of the control phasic twitch (n=22 cells). This shows that there must be another mechanism, besides Ca entry via Ca channels, by which membrane depolarisation can trigger sarcoplasmic reticular release and the phasic twitch. The phasic twitch that remained in the presence of nifedipine increased progressively with the magnitude of step depolarisation, required a functional sarcoplasmic reticulum, was abolished by 5 mM external nickel, and was sensitive to both the Na and Ca transmembrane gradients. Conclusions: The voltage dependent sarcolemmal Na-Ca exchange is predicted theoretically to generate a transient Ca entry at the start of a step membrane depolarisation, when membrane potential suddenly becomes more positive than the reversal potential of the Na-Ca exchange. The results of this study indicate that in rat myocytes with normal internal ions, physiological levels of membrane depolarisation generate a sufficient Ca entry on the exchange to trigger sarcoplasmic reticular calcium release and contraction. In the absence of ICa, this mechanism is capable of triggering a calcium release which leads to about 40% of the phasic contraction in cells depolarised from −40 mV to 0 mV. The existence of this sarcoplasmic triggering mechanism may have significance for the normal control of cardiac muscle contraction. Cardiovascular Research 1993;27:1677-1690
Developments in Digestive Diseases Clinical Relevance
Authors: M. Sarner
Journal: Gut (1978)

enteropathy and another almost as short on malabsorption syndromes.The choice of references, especially in the first part, is strangely arbitrary.The section on para- sitic diseases is better organised and pro- vides much useful data in compact form, and the last pages give a useful summary of the main antiparasitic drugs, with data on dosage and toxicity.
Polyunsaturated fatty acids in plasma, red blood cells and mononuclear cell phospholipids of patients with atopic dermatitis
Authors: R. Lindskou, G. Hølmer
Journal: Allergy (1992)

Recent studies of polyunsaturated fatty acids (PUFA) in plasma and blood cell components of patients with atopic diseases have indicated disordered fat metabolism as linoleic acid (18:2n‐6) tends to be increased while the more unsaturated fatty acids, such as gamma‐linolenic acid (18:3n‐6) and arachidonic acid (20:4n‐6) are present in decreased amounts. To further clarify these abnormalities, we examined the PUFA content in phospholipids derived from plasma, red blood cells and mononuclear cells (MNC) in patients with atopic dermatitis. In plasma no significant differences were found between patients and controls. In red blood cells dihomo‐gamma‐linolenic acid (20:3n‐6) was reduced in eczema patients, as compared with controls. The most significant findings in eczema patient MNC were reduced ratios of 20:4n‐6/20:3n‐6 in total lipids and in phosphatidyl ethanolamine (PE) and of 20:4n‐6/18:2n‐6 in both total lipids, phosphatidyl choline (PC) and PE. These findings indicate a disordered fatty acid metabolism in MNC of patients with atopic dermatitis. It is possible that these changes in the fatty acid profile of MNC may account for some of the immunological abnormalities seen in these patients.
Hormonal adaptation to the stresses imposed upon sodium balance by pregnancy and lactation in the Yanomama Indians, a culture without salt.
Authors: W J Oliver, J V Neel, R J Grekin, E L Cohen
Journal: Circulation (1981)

The Yanomama Indians of northern Brazil and southern Venezuela have been identified as a "no-salt" culture. In this study, data were obtained to determine in this population the adjustments of sodium-related hormones to the stresses imposed upon sodium balance by pregnancy and prolonged lactation. Controls against the possibility that findings in the Yanomama were ethnic rather than dietary were provided by similar observations in the Guaymi Indians of Panama, who have free access to salt. Urinary concentrations of sodium were approximately 1 mEq/l in male and female Yanomama, with 24-hour excretion rates in the males averaging 1 mEq, similar to our prior observation. The pregnant Yanomama had exceeding high urinary concentrations of aldosterone. These were associated with higher plasma renin activities and serum aldosterone concentrations than in all other subjects. Although pregnant Guaymi had elevations of serum and urinary aldosterone, these were significantly lower (p &lt; 0.001) than those of the Yanomama. Prolonged lactation in the Yanomama was associated with elevation of plasma renin activity and serum and urinary aldosterone concentration compared with the Guaymi, but were not higher than those in nonlactating Yanomama females. The findings suggest that pregnancy in a salt-poor environment is associated with an exaggerated augmentation of hormonal responses that enhance positive sodium balance.
New Radiotherapy and Chemoradiotherapy Approaches for Non–Small-Cell Lung Cancer
Authors: Joseph K. Salama, Everett E. Vokes
Journal: Journal of Clinical Oncology (2013)

Recent advances in systemic cytotoxic and molecularly targeted therapies coupled with technologic strides in radiotherapy have the potential to improve outcomes for patients with non-small-cell lung cancer (NSCLC). Investigations are ongoing to identify optimal cytotoxin-based chemoradiotherapy platforms. The influence of specific histologic and molecular mutation status on the combination of targeted therapies and radiotherapy is also being actively studied. Although there are no convincing randomized phase III data to date supporting a survival advantage for combining molecularly targeted agents with radiation or chemoradiotherapy in the setting of locally advanced NSCLC, phase II and III studies targeted to elderly patients and those with poor performance status are elucidating preferred chemoradiotherapy strategies. Radiotherapy dose escalation did not improve chemoradiotherapy outcomes, although increasing radiation dose-intensity with modern techniques is being actively studied. As modern radiotherapy techniques have been shown to improve outcomes of some patients with limited metastatic disease, investigations are ongoing regarding how to optimally integrate them with standard chemotherapy platforms.
TCT-359 Atherosclerotic Plaque Formation Relates to Myocardial Bridging in Left Anterior Descending Coronary Arteries
Authors: Shigemitsu Tanaka, Yuhei Kobayashi, Jennifer A. Tremmel, Ingela Schnittger, Paul Yock, Peter J. Fitzgerald, Yasuhiro Honda
Journal: Journal of the American College of Cardiology (2014)
Temporal Relation of the First Heart Sound to Closure of the Mitral Valve
Authors: SHLOMO LANIADO, EDWARD L. YELLIN, HYMAN MILLER, ROBERT W. M. FRATER
Journal: Circulation (1973)

The objective of this study is to describe the mechanism of production of the first heart sound (S 1 ). The temporal relation between the major components of S 1 and (1) cessation of flow across the mitral valve, (2) closure of the valve, and (3) time of peak rate of rise of left ventricular pressure (peak LV dP/dt), were investigated in open-chest dogs. Phasic flow across the mitral valve was recorded by a supraannular electromagnetic flow probe, and timing of valve closure was determined by synchronized cinefluorogram of the motion of the valve cusps after they were made radio opaque. Closure of the mitral valve did not occur at the crossing point of atrial and ventricular pressures (at the beginning of systole), but 20-40 msec later due to inertia of mitral flow. The first major component of the first sound coincided with two simultaneous events: cessation of mitral flow and closure of the valve. It did not show a fixed temporal relationship to time of peak dP/dt.
Emergent angioplasty for acute myocardial infarction at a community hospital without on-site cardiac surgery
Authors: Mandeep Singh, Kirk N. Garratt, Ryan J. Lennon, Michael A. Kjelsberg, Bernard J. Gersh, Peter B. Berger, Farris K. Timimi, Robert J. Houlihan, Kevin T. Cragun, Christopher H. Crocker, David R. Holmes, Henry H. Ting
Journal: Journal of the American College of Cardiology (2002)
Multiple Crystal Echocardiographic Evaluation of Endocardial Cushion Defect
Authors: DAVID J. SAHN, RICHARD W. TERRY, ROBERT O'ROURKE, GEORGE LEOPOLD, WILLIAM F. FRIEDMAN
Journal: Circulation (1974)

A prototype multiple crystal echocardiographic system developed by Bom and associates was used to evaluate cross-sectional cardiac anatomy in real time in twenty infants and children with endocardial cushion defect (ECD). The findings were compared to fifty normal infants and children and nineteen patients with normal mitral valve anatomy but right ventricular enlargement (RVE). Three standard transducer positions for evaluation of sagittal and transverse cardiac cross-sections are outlined and the normal group and RVE subgroup described. Studies in patients with ECD demonstrated several distinctive abnormalities, consisting of multiple echoes in the mitral valve area, anterior mitral leaflet - septal apposition in diastole with reduced posterior motion in systole, and reduced excursion of the anterior mitral leaflet. In patients with complete atrioventricular (A-V) canal defects, the anterior leaflet was often observed passing across the plane of the ventricular septum into the right ventricle during diastole, and in some of these patients the anterior mitral leaflet was related to the tricuspid annulus. Multiple crystal cardiac ultrasonography allows a more precise determination of intra- and extracardiac spatial relationships and is easier to perform than single crystal echo. The new technique provides clinical information helpful in evaluating patients with possible ECD and gives some indication of the severity of the defect.
The NF-κB regulator MALT1 determines the encephalitogenic potential of Th17 cells
Authors: Anne Brüstle, Dirk Brenner, Christiane B. Knobbe, Philipp A. Lang, Carl Virtanen, Brian M. Hershenfield, Colin Reardon, Sonja M. Lacher, Jürgen Ruland, Pamela S. Ohashi, Tak W. Mak
Journal: Journal of Clinical Investigation (2012)

Effector functions of inflammatory IL-17–producing Th (Th17) cells have been linked to autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). However, what determines Th17 cell encephalitogenicity is still unresolved. Here, we show that after EAE induction, mice deficient for the NF-κB regulator MALT1 (Malt1–/– mice) exhibit strong lymphocytic infiltration in the CNS, but do not develop any clinical signs of EAE. Loss of Malt1 interfered with expression of the Th17 effector cytokines IL-17 and GM-CSF both in vitro and in vivo. In line with their impaired GM-CSF secretion, Malt1–/– Th cells failed to recruit myeloid cells to the CNS to sustain neuroinflammation, whereas autoreactive WT Th cells successfully induced EAE in Malt1–/– hosts. In contrast, Malt1 deficiency did not affect Th1 cells. Despite their significantly decreased secretion of Th17 effector cytokines, Malt1–/– Th17 cells showed normal expression of lineage-specific transcription factors. Malt1–/– Th cells failed to cleave RelB, a suppressor of canonical NF-κB, and exhibited altered cellular localization of this protein. Our results indicate that MALT1 is a central, cell-intrinsic factor that determines the encephalitogenic potential of inflammatory Th17 cells in vivo.
From the bottom up: The roots of social neuroscience at risk of running dry?
Authors: Cindy Hamon-Hill, Simon Gadbois
Journal: Behavioral and Brain Sciences (2013)

A second-person neuroscience, as an emerging area of neuroscience and the behavioral sciences, cannot afford to avoid a bottom-up, subcortical, and conative-affective perspective. An example with canid social play and a modern motivational behavioral neursocience will illustrate our point.
Volunteer counsellors for supporting breast feeding: Support for breast feeding must be proactive
Authors: Annette E Hay
Journal: BMJ (2004)

EDITOR—Graffy et al's finding that offering voluntary support to breastfeeding mothers did not significantly affect breastfeeding rates is not surprising.1

Many will know the chaos caused by a new baby's arrival. Mounds of paperwork, presents, and clothes build up in most homes as the usual order is abandoned. Contact numbers and advice leaflets …
Freud as a Writer
Authors: Thomas H. Lewis
Journal: JAMA (1983)

This is a beautiful and valuable book. I wish that I had read it before reading Freud, but of course I wouldn't have then and can only be grateful that today it makes reading him an even richer experience. Mahony's book, in its own richness, is difficult to review. It has been on my desk for months, always a pleasure to return to, but its fascinations seem to place it illusively beyond synopsis. After all, how long can a review be allowed to be? Furthermore, one is caught up again and again in the reflexive turnings of writing about a writer writing about a writer.  Freud's Goethe Prize was for literature, and Albert Einstein, in a similar accolade, complimented him on his work from a literary point of view. Patrick Mahony helps us to read the 23 volumes of the Standard Edition, the Minutes of the Vienna Psychoanalytic Society , and
Chronic reduction of myocardial ischemia does not attenuate coronary collateral development in miniswine.
Authors: J D Symons, K F Pitsillides, J C Longhurst
Journal: Circulation (1992)

BACKGROUND Myocardial ischemia is considered to be a possible stimulus for development of the coronary collateral circulation. We therefore hypothesized that chronic reduction of myocardial oxygen demand to lessen ischemia would attenuate coronary collateral development over an 8-week period using left circumflex coronary artery (LCx) ameroid-induced constriction in pigs. METHODS AND RESULTS Collateral development was assessed by myocardial blood flow (radioactive microspheres) and left ventricular regional function (sonomicrometer dimension gauges). beta-Adrenoceptor blockade with propranolol (160 or 320 mg b.i.d.p.o.) was initiated in 15 animals 1 day after surgery. Compared with 16 untreated animals, beta-adrenoceptor antagonism was documented in the treated group by 1) pharmacological stimulation with isoproterenol, 2) physiological stimulation during graded treadmill exercise, and 3) repeated long-term biotelemetry recordings of oxygen demand (heart rate and blood pressure) and regional myocardial function. In addition to pharmacological and physiological verification of beta-blockade, biotelemetry showed that, compared with the untreated animals, propranolol significantly reduced the daily number, individual duration, and severity of events representing myocardial dysfunction. This suggests that in the beta-blocked group, little if any ischemia was present throughout the first 5 weeks when collateral growth occurs. Transmural myocardial blood flow (expressed as a ratio of flow in the LCx region to the nonoccluded region of the left ventricle) and systolic wall thickening in the LCx region were determined at rest and during treadmill exercise (240 beats per minute) 31-38 days (5 weeks) and 60-67 days (8 weeks) after surgery. Propranolol was withdrawn 3 days before flow and function determinations and was resumed immediately after testing. Blood flow ratios at 5 weeks decreased similarly from rest to exercise in the untreated (0.83 +/- 0.04 to 0.60 +/- 0.05, p less than 0.05) and beta-blockade group (0.82 +/- 0.09 to 0.57 +/- 0.10, p less than 0.05). Systolic wall thickening from rest to exercise was attenuated to the same degree in the untreated (59 +/- 6% to 38 +/- 6%, p less than 0.05) and beta-blockade group (50 +/- 8% to 30 +/- 5%, p less than 0.05). Similar flow and function responses were observed in both groups at 8 weeks. CONCLUSIONS We conclude that growth and development of the coronary collateral circulation measured functionally during exercise at 90% of maximal heart rate is unrelated to the extent and duration of myocardial ischemia in this model.
Predictive factors for histological discrepancy between endoscopic biopsies and endoscopic mucosal resection specimens in Barrett's dysplasia/early neoplasia
Authors: E. Telakis, V. Subramanian, J. Mannath, P. Kaye, K. Ragunathm
Journal: Gut (2011)

<h3>Introduction</h3> Accurate diagnosis of high grade dysplasia (HGD) or early cancer (EC) is of paramount importance in the management of Barrett9s oesophagus. Endoscopic biopsies are the standard method for the diagnosis of HGD/EC but discrepancies have been reported between biopsies and endoscopic mucosal resection (EMR) specimens. The aim of this study was to investigate the predictive factors for histological discrepancy between endoscopic biopsies and EMR specimens. <h3>Methods</h3> Prospectively collected data on all EMRs performed for Barrett9s HGD or EC in our institution over a 4-year period were analyzed. Histology of pre-resection biopsies and EMR specimens was retrieved from pathology records. Cases with diagnostic discrepancies between biopsies and EMRs were compared with those without discrepancies. Multivariate linear regression analysis was used with size of lesion, endoscopic morphology, length of Barrett9s, number of targeted biopsies, age and sex of patients as predictive factors. <h3>Results</h3> 59 lesions from 57 patients (43 men, mean age: 67 ± 11.2) who underwent EMR were studied. Mean length of Barrett9s was 5.2 ± 3.4 cm (range 1–13) and the mean size of lesions was 15.5 ± 4.9 mm (range 7–30 mm). Elevated (Paris 0-Is or 0-IIa) lesions were observed in 31 (52.5%) and flat/depressed lesions (0-IIb or 0-IIc) in 28 (47.5%) of cases. The mean number of pre-resection targeted biopsies was 3.1 ± 1.01 (range 1–5). The ‘band and snare’ mucosectomy technique was used in 46 (78%) and the cap-assisted technique in 13 (22%) EMR cases. Post-EMR histological diagnosis was HGD in 22 (37.3%) and carcinoma in 37 (62.7%) cases. The histological discrepancy rate was 44% (26/59). EMR upgraded the histological diagnosis in 22 (37.3%) cases and downgraded it in 4 (6.8%) resections. On multivariate linear regression analysis, &lt;3 targeted biopsies per lesion was the only independent predictive factor (p = 0.03) and was associated with 3.3-fold increase in histological discrepancy (OR = 3.3, 95% CI 1.1 to 9.9). Size of lesion, endoscopic morphology, length of Barrett9s, age and sex had no statistically significant effect. <h3>Conclusion</h3> Obtaining 3 or more targeted biopsies per lesion improves the histological correlation between endoscopic biopsies and EMR specimens in patients with Barrett9s early neoplasia.
Hemolysis and bilirubin conjugation in association with UDP-glucuronosyltransferase 1A1 promoter polymorphism
Authors: Michael Kaplan, Cathy Hammerman, Firmino F. Rubaltelli, Maria T. Vilei, Ephrat Levy-Lahad, Paul Renbaum, Hendrik J. Vreman, David K. Stevenson, Maurizio Muraca
Journal: Hepatology (2002)

Hemolysis may contribute to hyperbilirubinemia in Gilbert's syndrome. The authors examined blood carboxyhemoglobin corrected for inspired CO (COHbc) to index heme catabolism and serum conjugated bilirubin fractions to reflect bilirubin conjugation. Both parameters were related to UDP-glucuronosyltransferase 1A1 (UGT) promoter polymorphism, associated with Gilbert's syndrome, in term male newborns. COHbc was expressed as percentage of total hemoglobin, and total conjugated bilirubin (TCB) value as a percentage of serum total bilirubin (STB), (TCB/STB[%]). A production/conjugation index, COHbc/(TCB/STB[%]), represented bilirubin production divided by conjugation. UGT promoter genotype was designated according to the number of promoter TA insertions in each allele: 6/6, homozygous normal; 6/7, heterozygous; 7/7, homozygous variant. STB and COHbc values were higher in the 7/7 subgroup than the other counterparts (P <.01). The COHbc/(TCB/STB[%]) was higher in the 7/7 than either the 6/6 or 6/7 subsets (1.93 [1.31-2.88] vs. 0.85 [0.51-1.72] and 0.84 [0.53-1.87], respectively; P <.01). In conclusion, 7/7 UGT promoter polymorphism was associated with increased blood COHbc values (unexpected finding) as well as diminished serum total conjugated bilirubin ratios (expected finding). The increased hemolysis may contribute to the pathogenesis of increased STB values seen in Gilbert's syndrome, and exacerbate neonatal hyperbilirubinemia associated with the promoter polymorphism.
Exposure of fibrinogen receptors in human platelets by surface proteolysis with elastase.
Authors: E Kornecki, Y H Ehrlich, D D De Mars, R H Lenox
Journal: Journal of Clinical Investigation (1986)

Human platelets that were preincubated with porcine elastase aggregated spontaneously upon the addition of fibrinogen. Maximal aggregation to fibrinogen was observed with platelets pretreated with an elastase concentration of 111 micrograms/ml, and half-maximal aggregation occurred after treatment with 11 micrograms/ml elastase. Binding of radiolabeled fibrinogen to elastase-treated platelets was specific, saturable, and showed a single class of 48,400 +/- 9,697 fibrinogen-binding sites per platelet with a dissociation constant of 6.30 +/- 1.48 X 10(-7) M. ATP, apyrase, and the stimulators of platelet adenylate cyclase forskolin, prostaglandin E1, prostacyclin, and N6, 2'-O-dibutyryl cyclic AMP did not inhibit the fibrinogen-induced aggregation of elastase-treated platelets. EDTA completely blocked the initiation of aggregation and reversed the fibrinogen-induced aggregation of elastase-treated platelets. Monoclonal and polyclonal antibodies directed against glycoproteins (GP) IIb and IIIa completely blocked the fibrinogen-induced aggregation of elastase-treated platelets. Immunoprecipitates with these antibodies obtained from detergent extracts of surface-radiolabeled, intact, and elastase-treated platelets contained the glycoproteins IIb and IIIa. We conclude that surface proteolysis by low concentrations of elastase can expose fibrinogen-binding sites associated with GPIIb and GPIIIa on the platelet surface, resulting in spontaneous aggregation upon the addition of fibrinogen. These findings may be relevant to hemostatic changes observed in patients with increased levels of circulating elastase.