tbuckley/cabot-search huggingface dataset:
Pre-treatment with the Na/H exchange inhibitor cariporide delays cell-to-cell electrical uncoupling during myocardial ischemia
Authors: A RODRIGUEZSINOVAS, D GARCIADORADO, F PADILLA, J INSERTE, J BARRABES, M RUIZMEANA, L AGULLO, J SOLERSOLER
Journal: Cardiovascular Research (2003)

Objective: Inhibition of Na+–H+ exchange (NHE) delays the onset of myocardial rigor contracture during ischemia. The aim of this study was to analyse the effects of NHE inhibition on cell-to-cell electrical uncoupling during myocardial ischemia/reperfusion. Methods: Twenty-six isolated rat hearts and 23 in situ porcine hearts were submitted to no-flow ischemia followed by reperfusion, with or without pre-treatment with cariporide (7 μM in rats and 3 mg/kg in pigs). Ischemic rigor and hypercontracture, conduction velocity and myocardial electrical impedance were monitored. Results: Pre-treatment with cariporide delayed ATP depletion (luminescence assay in rat myocardium) and onset of rigor contracture (tension recordings or ultrasonic crystals) during ischemia both in rat and pig hearts (P<0.05). In addition, cariporide delayed the onset of sharp changes in tissue resistivity and phase angle in impedance recordings (four-electrode probes) from 10±1 to 13±1 min (P<0.001) in rat hearts, and from 22±1 to 38±2 min (P<0.001) in pigs. Blockade of impulse propagation (transmembrane action potentials in rat hearts) was also markedly delayed by cariporide (from 14±1 to 20±1 min, P<0.001). Reperfusion-induced LDH release in rat hearts and infarct size in pigs were markedly reduced by pre-treatment with cariporide. Conclusions: Inhibition of NHE with cariporide slows the progression of ischemic injury during myocardial ischemia, and delays the onset of cell-to-cell electrical uncoupling.
Hoppel, a P-like Element Without Introns: a P-Element Ancestral Structure or a Retrotranscription Derivative?
Authors: Daphné Reiss, Hadi Quesneville, Danielle Nouaud, Olivier Andrieu, Dominique Anxolabéhère
Journal: Molecular Biology and Evolution (2003)

An in silico search for P-transposable-element-related sequences in the Drosophila melanogaster genome allowed us to detect sequences that are similar to P-element transposases. These sequences are located in the central region of 3.4-kb Hoppel elements, a class II transposon. Polymerase chain reaction (PCR) analysis of the insertional polymorphism revealed that these elements are mobile. The 3.4-kb elements are the longest copies of this family ever found. They contain an open reading frame that is long enough to encode a transposase, suggesting that the 3.4-kb elements are the full-length copies of the Hoppel family. Multiple alignments of several P-element transposases from different species and the Hoppel-element-encoded peptide showed that all of the P-element introns and the 5' region of the transposase are absent from the Hoppel sequence. Sequence analysis combined with reverse transcriptase PCR analysis showed that the 3.4-kb Hoppel elements are intronless. P and Hoppel not only share similar amino acid sequences but also have terminal inverted repeats of the same length (31 bp), and their excision footprints present a similar structure, which suggests that their transposases are functionally very similar. Thus, we propose that the Hoppel element family be included in the P-element superfamily. Two evolutionary scenarios are discussed considering the presence /absence of introns within the P-element superfamily.
Mcl-1 Is a Novel Therapeutic Target for Human Sarcoma
Authors: Christiane Thallinger, Markus F. Wolschek, Helmut Maierhofer, Hans Skvara, Hubert Pehamberger, Brett P. Monia, Burkhard Jansen, Volker Wacheck, Edgar Selzer
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Little is known about the role that Mcl-1, an antiapoptotic Bcl-2 family member, plays in solid tumor biology and susceptibility to anticancer therapy. We observed that the Mcl-1 protein is widely expressed in human sarcoma cell lines of different histological origin (n = 7). Because the expression of antiapoptotic Bcl-2 family proteins can significantly contribute to the chemoresistance of human malignancies, we used an antisense strategy to address this issue in sarcoma. Experimental Design: SCID mice (n = 6/group) received s.c. injections of SW872 liposarcoma cells. After development of palpable tumors, mice were treated by s.c.-implanted miniosmotic pumps prefilled with saline or antisense or universal control oligonucleotides (20 mg/kg/day for 2 weeks). On days 2, 6, and 10, mice were treated with low-dose cyclophosphamide (35 mg/kg i.p) or saline control. During the experiments, tumor weight was assessed twice weekly by caliper measurements. On day 14, animals were sacrificed. Tumors were weighed and fixed in formalin for immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling analysis. Results: Mcl-1 antisense oligonucleotides specifically reduced Mcl-1 protein expression but produced no reduction in tumor weight compared with saline-treated control animals. Cyclophosphamide monotreatment caused only modest tumor weight reduction compared with saline control. However, use of Mcl-1 antisense oligonucleotides combined with cyclophosphamide clearly enhanced tumor cell apoptosis and significantly reduced tumor weight by more than two-thirds compared with respective control treatments. Conclusion: A combination of Mcl-1 antisense oligonucleotides with low-dose cyclophosphamide provides a synergistic antitumor effect and might qualify as a promising strategy to overcome chemoresistance in human sarcoma.
Physicians and Environmental Change—Reply
Authors: Paul S. Auerbach
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Mice that exclusively express TLR4 on endothelial cells can efficiently clear a lethal systemic Gram-negative bacterial infection
Authors: Graciela Andonegui, Hong Zhou, Daniel Bullard, Margaret M. Kelly, Sarah C. Mullaly, Braedon McDonald, Elizabeth M. Long, Stephen M. Robbins, Paul Kubes
Journal: Journal of Clinical Investigation (2009)

Recognition of LPS by TLR4 on immune sentinel cells such as macrophages is thought to be key to the recruitment of neutrophils to sites of infection with Gram-negative bacteria. To explore whether endothelial TLR4 plays a role in this process, we engineered and imaged mice that expressed TLR4 exclusively on endothelium (known herein as EndotheliumTLR4 mice). Local administration of LPS into tissue induced comparable neutrophil recruitment in EndotheliumTLR4 and wild-type mice. Following systemic LPS or intraperitoneal E. coli administration, most neutrophils were sequestered in the lungs of wild-type mice and did not accumulate at primary sites of infection. In contrast, EndotheliumTLR4 mice showed reduced pulmonary capillary neutrophil sequestration over the first 24 hours; as a result, they mobilized neutrophils to primary sites of infection, cleared bacteria, and resisted a dose of E. coli that killed 50% of wild-type mice in the first 48 hours. In fact, the only defect we detected in EndotheliumTLR4 mice was a failure to accumulate neutrophils in the lungs following intratracheal administration of LPS; this response required TLR4 on bone marrow–derived immune cells. Therefore, endothelial TLR4 functions as the primary intravascular sentinel system for detection of bacteria, whereas bone marrow–derived immune cells are critical for pathogen detection at barrier sites. Nonendothelial TLR4 contributes to failure to accumulate neutrophils at primary infection sites in a disseminated systemic infection.
A simple analogue computer for cardiac output determination by thermodilution
Authors: S. B. OLSSON, R. WASSEN, E. VARNAUSKAS, H. WALLMAN
Journal: Cardiovascular Research (1972)

Journal Article A simple analogue computer for cardiac output determination by thermodilution Get access S. BERTIL OLSSON, S. BERTIL OLSSON From the Medical Clinic I, Sahlgrenska Hospital, Göteborg, Sweden, and the Research Laboratory of Medical Electronics, Chalmers University, Göteborg, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar RUNE WASSÉN, RUNE WASSÉN From the Medical Clinic I, Sahlgrenska Hospital, Göteborg, Sweden, and the Research Laboratory of Medical Electronics, Chalmers University, Göteborg, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar ED VARNAUSKAS, ED VARNAUSKAS 1 From the Medical Clinic I, Sahlgrenska Hospital, Göteborg, Sweden, and the Research Laboratory of Medical Electronics, Chalmers University, Göteborg, Sweden 1 Present address: Afd. voor Cardiologie, Academisch Ziekenhuis, Leiden, Holland. Search for other works by this author on: Oxford Academic PubMed Google Scholar HENRY WALLMAN HENRY WALLMAN From the Medical Clinic I, Sahlgrenska Hospital, Göteborg, Sweden, and the Research Laboratory of Medical Electronics, Chalmers University, Göteborg, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 6, Issue 3, May 1972, Pages 303–308, https://doi.org/10.1093/cvr/6.3.303 Published: 01 May 1972
Homocystine-induced arteriosclerosis. The role of endothelial cell injury and platelet response in its genesis.
Authors: L A Harker, R Ross, S J Slichter, C R Scott
Journal: Journal of Clinical Investigation (1976)

The atherogenic mechanism of homocystinemia has been defined by measuring endothelial cell loss and regeneration, platelet consumption, and intimal lesion formation in a primate model. Three groups of baboons were studied: (a) 8 control animals; (b) 15 animals after 3 mo of continuous homocystinemia; and (c) 11 animals after 3 mo of combined homocystinemia and oral treatment with dipyridamole. Experimental homocystinemia caused patchy endothelial desquamation comprising about 10% of the aortic surface despite a 25-fold increase in endothelial cell regeneration. Neither endothelial cell loss nor regeneration was changed significantly by dipyridamole. Homocystine-induced vascular deendothelialization produced a threefold increase in platelet consumption that was interrupted by dipyridamole inhibition of platelet function. All homocystinemic animals developed typical arteriosclerotic or preatherosclerotic intimal lesions composed of proliferating smooth muscle cells averaging 10-15 cell layers surrounded by large amounts of collagen, elastic fibers, glycosaminoglycans, and sometimes lipid. Intimal lesion formation was prevented by dipyridamole therapy. We conclude that homocystine-induced endothelial cell injury resulted in arteriosclerosis through platelet-mediated intimal proliferation of smooth muscle cells that can be prevented by drug-induced platelet dysfunction.
Purchasing clinically effective care
Authors: J Hayward
Journal: BMJ (1994)

Research findings are often poorly translated into clinical practice. One example is the management of acute myocardial infarction, where the evidence of the effectiveness of aspirin and early thrombolysis is overwhelming.1,2 Despite this the proportion of patients receiving the treatment may be low.3,4 Ensuring that patients receive the best possible care should be important for all doctors.

Should purchasers care as well? The NHS Executive thinks so and believes that the issue should be addressed through contracting. Last December all fundholding general practitioners, trusts, and health authorities received a letter from the executive urging them to take clinical effectiveness and clinical guidelines into account in contracting.5 Seven guidelines were attached for consideration, with the hope that purchasers would include at least one of them in their contracts.

The NHS Executive clearly believes that clinical effectiveness should form …
Vascular responses after alpha adrenergic receptor blockade
Authors: Francois M. Abboud, Phillip G. Schmid, John W. Eckstein
Journal: Journal of Clinical Investigation (1968)

Experiments were done to test the hypothesis that alpha receptor blockers antagonize more effectively venous than arterial responses to norepinephrine in man.Systemic arterial blood pressure, venous pressure in the forearm, blood flow through the forearm, and the volume of the forearm at a venous pressure of 30 mm Hg were measured using pressure transducers and a mercury strain-gauge plethysmograph. Infusions of norepinephrine into the brachial artery reduced forearm blood flow and venous distensibility without changing arterial pressure. After intraarterial infusion of phentolamine the decrease in venous distensibility during administration of norepinephrine was blocked almost completely whereas the decrease in blood flow through the forearm was not altered.The results indicate that alpha adrenergic receptor blockade can antagonize constriction of capacitance vessels more effectively than constriction of resistance vessels.
Presence of Epstein-Barr Virus DNA in Carcinomas of the Palatine Tonsil
Authors: B Brichácek, I Hirsch, O Síbl, E Vilikusová, V Vonka
Journal: JNCI Journal of the National Cancer Institute (1984)

The presence of Epstein-Barr virus genetic material was demonstrated in thin sections of biopsy specimens in 6 of 7 carcinomas of human palatine tonsil by the in situ hybridization test. The biopsy specimens from 4 tonsillar carcinomas exhibited a strong positive reaction; two biopsy specimens were weakly positive. Two tumor-free biopsy specimens were negative. None of the thin sections reacted with 3H-labeled herpes simplex virus DNA probe.
Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation
Authors: Yumiko Nishikawa, Fumiko Hirota, Masashi Yano, Hiroyuki Kitajima, Jun-ichi Miyazaki, Hiroshi Kawamoto, Yasuhiro Mouri, Mitsuru Matsumoto
Journal: The Journal of Experimental Medicine (2010)

The roles of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) in the organization of the thymic microenvironment for establishing self-tolerance are enigmatic. We sought to monitor the production and maintenance of Aire-expressing mTECs by a fate-mapping strategy in which bacterial artificial chromosome transgenic (Tg) mice expressing Cre recombinase under the control of the Aire regulatory element were crossed with a GFP reporter strain. We found that, in addition to its well recognized expression within mature mTECs, Aire was expressed in the early embryo before emergence of the three germ cell layers. This observation may help to explain the development of ectodermal dystrophy often seen in patients with AIRE deficiency. With the use of one Tg line in which Cre recombinase expression was confined to mTECs, we found that Aire(+)CD80(high) mTECs further progressed to an Aire(-)CD80(intermediate) stage, suggesting that Aire expression is not constitutive from after its induction until cell death but instead is down-regulated at the beginning of terminal differentiation. We also demonstrated that many mTECs of Aire-expressing lineage are in close contact with thymic dendritic cells. This close proximity may contribute to transfer of tissue-restricted self-antigens expressed by mTECs to professional antigen-presenting cells.
Functional effects of 13 rare<i>PRSS1</i>variants presumed to cause chronic pancreatitis
Authors: Andrea Schnúr, Sebastian Beer, Heiko Witt, Péter Hegyi, Miklós Sahin-Tóth
Journal: Gut (2013)

<h3>Objective</h3> Hereditary pancreatitis is caused by mutations in human cationic trypsinogen (<i>PRSS1</i>) which lead to increased autoactivation by altering chymotrypsin C (CTRC)-dependent trypsinogen activation and degradation. Exceptions are some cysteine mutations which cause misfolding, intracellular retention and endoplasmic reticulum stress. Clinical relevance of many <i>PRSS1</i> variants found in patients with sporadic chronic pancreatitis is unknown but often assumed by analogy with known disease-causing mutations. Functional comparison of <i>PRSS1</i> variants found in sporadic and hereditary cases is needed to resolve this dilemma. <h3>Design</h3> Here, we investigated the functional phenotype of 13 published <i>PRSS1</i> variants with respect to autoactivation in the presence of CTRC and cellular secretion. <h3>Results</h3> Only mutation p.D100H increased trypsinogen autoactivation, but this gain in function was offset by a marked reduction in secretion. Five mutants (p.P36R, p.G83E, p.I88N, p.V123M, p.S124F) showed decreased autoactivation due to increased degradation by CTRC. Five mutants exhibited strongly (p.D100H, p.C139F) or moderately (p.K92N, p.S124F, p.G208A) reduced secretion, whereas mutant p.K170E showed slightly increased secretion. Mutant p.I88N was also secreted to higher levels but was rapidly degraded by CTRC. Finally, three mutants (p.Q98K, p.T137M, p.S181G) had no phenotypic alterations relative to wild-type trypsinogen. <h3>Conclusions</h3> Rare <i>PRSS1</i> variants found in sporadic chronic pancreatitis do not stimulate autoactivation but may cause increased degradation, impaired secretion or no functional change. Variants with reduced secretion are likely pathogenic due to mutation-induced misfolding and consequent endoplasmic reticulum stress.
Effect of vasopeptidase inhibitor omapatrilat on cardiomyocyte apoptosis and ventricular remodeling in rat myocardial infarction
Authors: Tom Bäcklund, Eeva Palojoki, Antti Saraste, Tina Grönholm, Anders Eriksson, Päivi Lakkisto, Olli Vuolteenaho, Markku S Nieminen, Liisa-Maria Voipio-Pulkki, Mika Laine, Ilkka Tikkanen
Journal: Cardiovascular Research (2003)

We have shown earlier that cardiomyocyte apoptosis continues at a high level late after myocardial infarction and contributes to adverse cardiac remodeling. Here we studied whether this process can be inhibited by the vasopeptidase inhibitor omapatrilat, a drug which causes simultaneous inhibition of both angiotensin converting enzyme and neutral endopeptidase. Our hypothesis was that omapatrilat-treated rats would have less cardiomyocyte apoptosis, and less adverse cardiac remodeling compared to rats treated with selective inhibitors of angiotensin converting enzyme, neutral endopeptidase or placebo. Myocardial infarction was produced by ligation of the left anterior descending coronary artery. Rats were randomized to receive omapatrilat, captopril, neutral endopeptidase inhibitor SQ-28603 or vehicle. Rats treated with omapatrilat and captopril had reduced cardiac BNP mRNA levels and less myocardial fibrosis by comparison with the vehicle-treated rats. However, omapatrilat was more effective than captopril in attenuating hypertrophy as measured by relative cardiac weight (3.0±0.2 vs. 3.8±0.2 mg/g, P<0.01) or by echocardiographically determined left ventricular mass (0.61±0.05 vs. 0.83±0.06 g, P<0.01). Myocardial apoptosis was elevated both in the infarction border zone (0.129±0.017%) and in the remote area (0.035±0.005%) still 4 weeks after myocardial infarction. Angiotensin converting enzyme inhibition proved to be important in the prevention of apoptosis since both omapatrilat and captopril reduced the number of apoptotic myocytes whereas selective neutral endopeptidase inhibitor SQ-28603 had no effect. In conclusion, myocardial apoptosis, remaining increased 4 weeks after myocardial infarction, was reduced by angiotensin converting enzyme inhibition. Vasopeptidase inhibition was more effective than selective angiotensin converting enzyme inhibition in preventing adverse cardiac remodeling after myocardial infarction.
Discussion
Authors: N Block
Journal: Trends in Neurosciences (1996)

There are two concepts of consciousness, access consciousness and phenomenal consciousness. But just as the concepts of water and H2O are different concepts of the same thing, so the two concepts of consciousness might come to the same thing in the brain. Some recent papers by Crick and Koch raise issues that suggest that these two concepts of consciousness might have different (though overlapping) neural correlates, despite Crick and Koch's implicit rejection of this idea.
Effect of atrial natriuretic peptide on coronary collateral blood flow.
Authors: B Foreman, X Z Dai, D C Homans, D D Laxson, R J Bache
Journal: Circulation Research (1989)

This study was carried out to examine the effects of atrial natriuretic peptide on coronary collateral blood flow. Studies were performed in nine adult mongrel dogs 3.4 months after embolic occlusion of the left anterior descending coronary artery had been performed to stimulate collateral vessel growth. At the time of study the anterior descending coronary artery was cannulated to allow estimation of interarterial collateral flow from measurements of retrograde blood flow. Injection of radioactive microspheres during retrograde flow collection allowed simultaneous determination of continuing tissue flow for evaluation of microvascular collateral communications. Atrial natriuretic peptide in doses of 20 and 200 micrograms administered into the left atrium resulted in 17 +/- 3.0% and 34 +/- 4.5% increases in retrograde flow, respectively (each p less than 0.01). Tissue flow in the collateral dependent myocardial region did not change in response to atrial natriuretic peptide. After the larger dose of atrial natriuretic peptide, the administration of nitroglycerin (10 micrograms/kg into the left atrium) caused no further increase of retrograde blood flow, and no further decrease of collateral vascular resistance. These data indicate that atrial natriuretic peptide causes vasodilation of moderately well-developed interarterial coronary collateral vessels.