tbuckley/cabot-search huggingface dataset:
CPAP versus Oxygen in Obstructive Sleep Apnea
Authors: Daniel J. Gottlieb, Naresh M. Punjabi, Reena Mehra, Sanjay R. Patel, Stuart F. Quan, Denise C. Babineau, Russell P. Tracy, Michael Rueschman, Roger S. Blumenthal, Eldrin F. Lewis, Deepak L. Bhatt, Susan Redline
Journal: New England Journal of Medicine (2014)

Obstructive sleep apnea is associated with hypertension, inflammation, and increased cardiovascular risk. Continuous positive airway pressure (CPAP) reduces blood pressure, but adherence is often suboptimal, and the benefit beyond management of conventional risk factors is uncertain. Since intermittent hypoxemia may underlie cardiovascular sequelae of sleep apnea, we evaluated the effects of nocturnal supplemental oxygen and CPAP on markers of cardiovascular risk.We conducted a randomized, controlled trial in which patients with cardiovascular disease or multiple cardiovascular risk factors were recruited from cardiology practices. Patients were screened for obstructive sleep apnea with the use of the Berlin questionnaire, and home sleep testing was used to establish the diagnosis. Participants with an apnea-hypopnea index of 15 to 50 events per hour were randomly assigned to receive education on sleep hygiene and healthy lifestyle alone (the control group) or, in addition to education, either CPAP or nocturnal supplemental oxygen. Cardiovascular risk was assessed at baseline and after 12 weeks of the study treatment. The primary outcome was 24-hour mean arterial pressure.Of 318 patients who underwent randomization, 281 (88%) could be evaluated for ambulatory blood pressure at both baseline and follow-up. On average, the 24-hour mean arterial pressure at 12 weeks was lower in the group receiving CPAP than in the control group (-2.4 mm Hg; 95% confidence interval [CI], -4.7 to -0.1; P=0.04) or the group receiving supplemental oxygen (-2.8 mm Hg; 95% CI, -5.1 to -0.5; P=0.02). There was no significant difference in the 24-hour mean arterial pressure between the control group and the group receiving oxygen. A sensitivity analysis performed with the use of multiple imputation approaches to assess the effect of missing data did not change the results of the primary analysis.In patients with cardiovascular disease or multiple cardiovascular risk factors, the treatment of obstructive sleep apnea with CPAP, but not nocturnal supplemental oxygen, resulted in a significant reduction in blood pressure. (Funded by the National Heart, Lung, and Blood Institute and others; HeartBEAT ClinicalTrials.gov number, NCT01086800 .).
Drug-induced torsades de pointes — A form of mechano-electric feedback?
Authors: L FABRITZ
Journal: Cardiovascular Research (2007)

See article by Gallacher et al.  [1]  (pages 247–256) in this issue. 

In this issue of Cardiovascular Research , Gallacher et al. report findings on a novel canine model of drug-induced long-QT syndrome [1]. In this model, torsades de pointes (TdP) arrhythmia was induced in anaesthetised dogs by bolus injections of the β-adrenoreceptor agonist isoproterenol during selective inhibition of the slow component of the delayed-rectifier potassium current I Ks by HMR1556. Isoproterenol induced TdP in 94% of dogs tested. Authors examined the interaction of putative mechanisms of induction of TdP. Blockade of I Ks mimics the functional effects of the genetic alterations found in long-QT syndrome type I. The β-adrenergic challenge caused action potential prolongation and increased spatial [2–4] and temporal [2] dispersion of repolarisation. Systolic aftercontractions, measured as small increases in left ventricular systolic pressure, preceded the onset of TdP (see Fig. 4 in the manuscript). TdP and aftercontractions were able to be suppressed by either β-adrenoreceptor blockade by esmolol or calcium channel blockade by verapamil, as expected [5,6].

The simultaneous real-time recording of surface ECG, several monophasic action potentials (MAP), and pressure from both ventricles in the dog gives us valuable insight into the … 

*Tel.: +49 251 83 46034; fax: +49 251 83 47864. fabritzl{at}uni-muenster.de
A J Williams--a tropical veterinary pioneer
Authors: G R Durrant
Journal: Journal of the Royal Society of Medicine (2003)

Many of the early developments in human and veterinary medicine were brought about by members of the military medical and veterinary services. This is particularly true of tropical diseases. For example, the organism Trypanosoma evansi reminds us that, in 1880, Colonel Griffith Evans MD FRCVS, of the Army Veterinary Service, postulated the pathogenicity of the trypanosome and its spread by fly bites. Initially the idea was bluntly rejected by his military medical superiors. It was largely the study of his report by Koch and Pasteur that led to Evans' recognition as discoverer of the pathogenicity of the trypanosome1—truly a landmark in tropical medicine. Recently, when visiting a veterinary colleague, I met a retired colonel of the Royal Marines whose grandfather had been Director of Veterinary Services in India 1928–1932. He too, I found, made striking contributions to tropical veterinary medicine.
Nuclear βII-Tubulin Associates with the Activated Notch Receptor to Modulate Notch Signaling
Authors: Tien-Shun Yeh, Rong-Hong Hsieh, Shing-Chuan Shen, Shwu-Huey Wang, Min-Jen Tseng, Chwen-Ming Shih, Jing-Jer Lin
Journal: Cancer Research (2004)

Abstract The Notch signal pathway plays important roles in proliferation, apoptosis, and differentiation. Abnormalities in Notch signaling are linked to many human diseases. After ligand binding, Notch signaling is activated through the cleavage of Notch receptors to release and translocate the Notch intracellular domain into the nucleus. The Notch1 receptor intracellular domain (N1IC), the activated form of the Notch1 receptor, can modulate downstream target genes via C promoter-binding factor 1–dependent and -independent pathways. To further dissect the Notch1 signaling pathway, we screened the N1IC-associated proteins using a yeast two-hybrid system and identified nuclear βII-tubulin as a candidate for the N1IC-associated proteins. It was suggested that the presence of βII-tubulin in nuclei might be correlated with the cancerous state of cells. However, the function of βII-tubulin locating in the nucleus still is unknown. Herein, we show that the complex of α- and βII-tubulin is associated with N1IC in cancer cells by a coimmunoprecipitation analysis. The ankyrin domain of the Notch1 receptor alone was sufficient to associate with βII-tubulin. Furthermore, α- and βII-tubulin were localized in the nucleus and formed a complex with N1IC. Treatment with Taxol increased the amounts of nuclear α- and βII-tubulin in K562 and HeLa cells and promoted the C promoter-binding factor 1–dependent transactivation activity of N1IC. We also show that nuclear βII-tubulin was bound on the C promoter-binding factor 1 response elements via the association with N1IC. These results suggest that nuclear βII-tubulin can modulate Notch signaling through interaction with N1IC in cancer cells.
Paradoxical bradycardia following the administration of sodium nitroprusside in the rat is abolished by indomethacin
Authors: P. LUKACSKO
Journal: Cardiovascular Research (1982)

Journal Article Paradoxical bradycardia following the administration of sodium nitroprusside in the rat is abolished by indomethacin Get access PETER LUKACSKO PETER LUKACSKO * From the Department of Pharmacology, Smith Kline & French Laboratories, Philadelphia *Address reprint requests to: Dr Peter Lukacsko, Dept of Pharmacology, Smith Kline & French Laboratories, Philadelphia, PA 19101, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 16, Issue 2, February 1982, Pages 95–98, https://doi.org/10.1093/cvr/16.2.95 Published: 01 February 1982
Changing Prevalence of Overweight Children and Adolescents at Onset of Insulin-Treated Diabetes
Authors: Ingrid M. Libman, Massimo Pietropaolo, Silva A. Arslanian, Ronald E. LaPorte, Dorothy J. Becker
Journal: Diabetes Care (2003)

OBJECTIVE—The aim of this study was to compare the prevalence of being overweight in black and white children and adolescents at onset of insulin-treated diabetes during two time periods: 1979–1989 (period I) and 1990–1998 (period II). RESEARCH DESIGN AND METHODS—All black children &amp;lt;19 years of age diagnosed with diabetes and treated with insulin at onset admitted to the Children’s Hospital of Pittsburgh between January 1979 and December 1998 were matched with white children by sex, age at onset, and year of diagnosis. Data were obtained from a review of medical records. Overweight was defined as BMI ≥85th percentile for age and sex. Islet cell autoantibodies were measured. RESULTS—The prevalence of being overweight increased from 12.6% (period I) to 36.8% (period II) (P = 0.0003); in whites from 2.9 to 16.6% (P = 0.04) and in blacks from 22 to 55% (P = 0.001); and in the age-group &amp;lt;11 years from 7.3 to 22.2% (P = 0.04) and age 11–18 years from 20 to 50% (P = 0.006). In children with at least one antibody, the prevalence of being overweight increased from 5.1 to 24.4% (P = 0.001). In the multivariate logistic regression, period of diagnosis (period II), race (black), age at onset (≥11 years old), and absence of autoimmunity were associated with being overweight. CONCLUSIONS—At onset of the disease, the prevalence of being overweight has tripled from the 1980s to the 1990s, following the trend in the general population. Weight gain may be an accelerating factor for onset of insulin-treated diabetes and may have contributed to the increased incidence of diabetes in youth seen in some populations.
Natural Killer T Cell–derived IL-17 Mediates Lung Ischemia–Reperfusion Injury
Authors: Ashish K. Sharma, Damien J. LaPar, Yunge Zhao, Li Li, Christine L. Lau, Irving L. Kron, Yoichiro Iwakura, Mark D. Okusa, Victor E. Laubach
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

We recently implicated a role for CD4(+) T cells and demonstrated elevated IL-17A expression in lung ischemia-reperfusion (IR) injury. However, identification of the specific subset of CD4(+) T cells and their mechanistic role in IR injury remains unknown.We tested the hypothesis that invariant natural killer T (iNKT) cells mediate lung IR injury via IL-17A signaling.Mice underwent lung IR via left hilar ligation. Pulmonary function was measured using an isolated lung system. Lung injury was assessed by measuring edema (wet/dry weight) and vascular permeability (Evans blue dye). Inflammation was assessed by measuring proinflammatory cytokines in lungs, and neutrophil infiltration was measured by immunohistochemistry and myeloperoxidase levels.Pulmonary dysfunction (increased airway resistance and pulmonary artery pressure and decreased pulmonary compliance), injury (edema, vascular permeability), and inflammation (elevated IL-17A; IL-6; tumor necrosis factor-α; monocyte chemotactic protein-1; keratinocyte-derived chemokine; regulated upon activation, normal T-cell expressed and secreted; and neutrophil infiltration) after IR were attenuated in IL-17A(-/-) and Rag-1(-/-) mice. Anti-IL-17A antibody attenuated lung dysfunction in wild-type mice after IR. Reconstitution of Rag-1(-/-) mice with wild-type, but not IL-17A(-/-), CD4(+) T cells restored lung dysfunction, injury, and inflammation after IR. Lung dysfunction, injury, IL-17A expression, and neutrophil infiltration were attenuated in Jα18(-/-) mice after IR, all of which were restored by reconstitution with wild-type, but not IL-17A(-/-), iNKT cells. Flow cytometry and enzyme-linked immunosorbent spot assay confirmed IL-17A production by iNKT cells after IR.These results demonstrate that CD4(+) iNKT cells play a pivotal role in initiating lung injury, inflammation, and neutrophil recruitment after IR via an IL-17A-dependent mechanism.
Bone mineral density in patients with atopic dermatitis
Authors: K. AALTO-KORTE, M. TURPEINEN
Journal: British Journal of Dermatology (1997)

With the aim of evaluating the systemic effect of glucocorticoids (GCs), we measured bone mineral density (BMD) in 29 adult patients with chronic atopic dermatitis. BMD was measured in the lumbar spine and in the left femoral neck using dual-energy X-ray absorptiometry (DEXA). In the right calcaneus, BMD was measured using broad-spectrum ultrasound attenuation (BUA). For BMD, the patients with dermatitis did not differ from healthy controls. We did not find any statistically significant correlation between BMD and single risk factors, such as the barrier function of the skin (P = 0.08), the duration of the dermatitis (P = 0.58), and the use of oral GCs (P = 0.27) and potent topical GCs (P = 0.10). However, selected patients with severe disease, needing topical GCs of higher potency than hydrocortisone (HC), had lower values for lumbar BMD than the patients who had not used these preparations (-1.0 vs. +0.1 SD; P = 0.026). The lower lumbar BMD in this group could be explained by a long-term systemic effect of GCs.
Long-term outcome of patients with unexplained syncope treated with an electrophysiologic-guided approach in the implantable cardioverter-defibrillator era
Authors: Suneet Mittal, Sei Iwai, Kenneth M Stein, Steven M Markowitz, David J Slotwiner, Bruce B Lerman
Journal: Journal of the American College of Cardiology (1999)

OBJECTIVES We evaluated the long-term outcome of patients with coronary artery disease and unexplained syncope who were treated with an electrophysiologic (EP)-guided approach. BACKGROUND Electrophysiologic studies are frequently performed to evaluate unexplained syncope in patients with coronary artery disease. Patients with this profile who have inducible ventricular tachycardia are considered at high risk for sudden death and increased overall mortality, and therefore are often treated with an implantable cardioverter-defibrillator (ICD). The impact of this EP-guided strategy is unknown because there are no data comparing the long-term outcome of ICD recipients with that of noninducible patients. METHODS We evaluated 67 consecutive patients with coronary artery disease and unexplained syncope. All patients were treated with an EP-guided approach that included ICD implantation in patients with inducible ventricular tachycardia. RESULTS Electrophysiologic testing suggested a plausible diagnosis in 32 (48%) of these patients. Inducible monomorphic ventricular tachycardia was the most common abnormality. Despite frequent appropriate therapy with ICDs, the total mortality for patients with inducible monomorphic ventricular tachycardia was significantly higher than for noninducible patients. The respective one- and two-year survival rates were 94% and 84% in noninducible patients and 77% and 45% in inducible patients (p = 0.02). CONCLUSIONS Electrophysiologic testing suggests an etiology for unexplained syncope in approximately 50% of patients and risk stratifies these patients with regard to long-term outcome. Patients who receive an ICD for the management of inducible ventricular tachycardia have a high incidence of spontaneous ventricular arrhythmias requiring ICD therapy. However, despite ICD implantation and frequent appropriate delivery of ICD therapies, patients with inducible ventricular tachycardia have a significantly worse prognosis than do those who are noninducible.
The IL-10 and IFN-γ pathways are essential to the potent immunosuppressive activity of cultured CD8+ NKT-like cells
Authors: Li Zhou, Hongjie Wang, Xing Zhong, Yulan Jin, Qing-Sheng Mi, Ashok Sharma, Richard A McIndoe, Nikhil Garge, Robert Podolsky, Jin-Xiong She
Journal: Genome biology (2008)

Abstract Background CD8 + NKT-like cells are naturally occurring but rare T cells that express both T cell and natural killer cell markers. These cells may play key roles in establishing tolerance to self-antigens; however, their mechanism of action and molecular profiles are poorly characterized due to their low frequencies. We developed an efficient in vitro protocol to produce CD8 + T cells that express natural killer cell markers (CD8 + NKT-like cells) and extensively characterized their functional and molecular phenotypes using a variety of techniques. Results Large numbers of CD8 + NKT-like cells were obtained through culture of naïve CD8 + T cells using anti-CD3/anti-CD28-coated beads and high dose IL-2. These cells possess potent activity in suppressing the proliferation of naïve responder T cells. Gene expression profiling suggests that the cultured CD8 + NKT-like cells and the naïve CD8 + T cells differ by more than 2-fold for about 3,000 genes, among which 314 are upregulated by more than 5-fold and 113 are upregulated by more than 10-fold in the CD8 + NKT-like cells. A large proportion of the highly upregulated genes are soluble factors or surface markers that have previously been implicated in immune suppression or are likely to possess immunosuppressive properties. Many of these genes are regulated by two key cytokines, IL-10 and IFN-γ. The immunosuppressive activities of cells cultured from IL-10 -/- and IFN-γ -/- mice are reduced by about 70% and about 50%, respectively, compared to wild-type mice. Conclusion Immunosuppressive CD8 + NKT-like cells can be efficiently produced and their immunosuppressive activity is related to many surface and soluble molecules regulated by IL-10 and IFN-γ.
Schnitzler syndrome: heterogeneous immunopathologicalfindings involving IgM-skin interactions
Authors: D. Lipsker, D. Spehner, R. Drillien, P. Schmitt, B. Cribier, E. Heid, R-L. Humbel, E. Grosshans
Journal: British Journal of Dermatology (2000)

The Schnitzler syndrome is the association of chronic urticaria, intermittent fever, osteosclerotic bone lesions and a monoclonal IgM gammopathy. It is not yet firmly established whether the monoclonal immunoglobulin component plays a part in the pathophysiology of the urticarial lesions. Immunoblotting on epidermal and dermal human skin extracts as well as immunoelectron microscopic (IEM) studies on Lowicryl K4M-embedded skin sections were performed in three patients with the Schnitzler syndrome. Western blotting on epidermal extracts showed the presence of IgM-kappa antiskin autoantibodies in two patients. These antibodies displayed the same isotype as the monoclonal components and recognized a 280-290-kDa antigen in one patient and a 200-kDa antigen in the other patient. IEM studies showed sparse IgM deposits in the epidermis, around the keratinocytes, near the desmosomes in one patient and dense deposits below the lamina densa, in the region of the anchoring fibrils, in another patient. Antiskin IgM autoantibodies of the same isotype as their monoclonal gammopathies can be present in the serum of some patients with the Schnitzler syndrome. These IgM antibodies seem to deposit in vivo in the epidermis and at the dermal-epidermal junction, in the region of the anchoring fibrils. These findings suggest that the monoclonal gammopathy plays a part in the pathophysiology of the skin rash. They also suggest patient heterogeneity both in the skin antigens that are recognized as well as in their localization.
Inhibitor of Differentiation 1 Contributes to Head and Neck Squamous Cell Carcinoma Survival via the NF-κB/Survivin and Phosphoinositide 3-Kinase/Akt Signaling Pathways
Authors: Jizhen Lin, Zhong Guan, Chuan Wang, Ling Feng, Yiqing Zheng, Emiro Caicedo, Ellalane Bearth, Jie-Ren Peng, Patrick Gaffney, Frank G. Ondrey
Journal: Clinical Cancer Research (2009)

Abstract Purpose: A key issue in cancer is apoptosis resistance. However, little is known about the transcription factors that contribute to cellular survival of head and neck squamous cell carcinoma (HNSCC). Experimental Design: Three batches (54, 64, and 38) of HNSCC specimens were used for cellular and molecular analyses to determine the major molecular signaling pathways for cellular survival in HNSCC. Animal models (cell culture and xenografts) were used to verify the importance of apoptosis resistance in HNSCC. Results: Inhibitor of differentiation (Id) family member, Id1, was significantly upregulated in clinical HNSCC specimens and acted to protect keratinocytes from apoptosis. Transfection of HNSCC cells with Id1 in vitro induced the phosphorylation of Akt (p-Akt) via phosphoinositide 3-kinase and increased the expression of survivin via NF-κB. Blockage of both pathways by specific inhibitors (LY294002 and IκBαM, respectively) abrogated Id1-induced cell survival of keratinocytes. In vivo studies showed that increased expression of Id1 allowed nontumorigenic keratinocytes (Rhek-1A) to become tumorigenic in nude mice by increased expression of survival genes such as p-Akt and survivin. More importantly, short interfering RNA for Id1 significantly reduced HNSCC tumor volume of HNSCC in xenograft studies. Analysis of clinical data verified the importance of the Id1 downstream molecule, survivin, in the prognosis of HNSCC patients. Conclusions: The above data, taken together, suggest that Id1 and its downstream effectors are potential targets for treatment of HNSCC because of their contribution to apoptosis resistance. Clin Cancer Res; 16(1); 77–87
SOME QUESTIONS RELATING TO THE VIRULENCE OF MICRO-ORGANISMS WITH PARTICULAR REFERENCE TO THEIR IMMUNIZING POWERS
Authors: Richard P. Strong
Journal: The Journal of Experimental Medicine (1905)

The virulent cholera spirillum possesses a greater number of bacteriolytic and agglutinable haptophore groups, or these groups are endowed with a greater avidity for uni- and amboceptors than the avirulent. The number or the avidity of the bacteriolytic receptors possessed by a bacterium is directly proportional to its virulence. However, the agglutinable receptors do not follow this law, i.e., the agglutinable haptophore groups are not necessarily present in the same proportion as the bactericidal ones. While the energy of growth is a very important factor in relation to virulence, other phenomena must also be considered. The virulent organism possesses a greater number of toxic haptophore groups than the avirulent. The binding power of the free receptors of the organisms for bacteriolytic amboceptors in vitro is proportional to the bactericidal immunity produced in animals by each, which latter is in turn proportional to the virulence of the organisms from which the receptors were extracted. The binding power in vitro of the dead micro-organisms of different virulence for bacteriolytic amboceptors is not in proportion to their toxicity. The bactericidal immunity obtained by means of the inoculation with the dead organisms of different virulence, or their extracts obtained by autolytic digestion, is proportional to the virulence of the living strains of the bacteria employed. With the living organisms, while the bactericidal immunity obtained from the inoculation of animals with the virulent organism is greater than that produced with the avirulent, such immunity is not in direct proportion to the virulence of the bacteria introduced. These conclusions apply to the two strains of cholera spirilk employed in the foregoing experiments. Whether they will also hold good with other strains of this spirillum or for micro organisms in general, must be decided by further experimenta work.