tbuckley/cabot-search huggingface dataset:
The effect of an NADH oxidase inhibitor (hydrocortisone) on polymorphonuclear leukocyte bactericidal activity
Authors: Gerald L. Mandell, Walter Rubin, Edward W. Hook
Journal: Journal of Clinical Investigation (1970)

Polymorphonuclear neutrophils (PMN) from patients with chronic granulomatous disease of childhood have impaired bactericidal activity and are deficient in diphosphopyridine nucleotide, reduced form of, (NADH) oxidase. Since hydrocortisone had been shown to inhibit NADH oxidation, experiments were undertaken to determine the effect of hydrocortisone on several parameters of human PMN function. The phagocytic and bactericidal capacity of PMN with or without hydrocortisone (2.1 mM) was determined by quantitation of cell-free, cell-associated, and total bacteria. Phagocytosis of Staphylococcus aureus and several gram-negative rods was unimpaired by the presence of hydrocortisone in the media. In contrast, killing of bacteria was markedly impaired by hydrocortisone. After 30 min of incubation, there were 20-400 times as many bacteria surviving in hydrocortisone-treated PMN as in simultaneously run controls without hydrocortisone. The defect of intracellular killing noted in the presence of hydrocortisone was not related to impaired degranulation. Quantitative kinetic studies of degranulation revealed no difference in the release of granule associated acid phosphatase in hydrocortisone-treated and control PMN after phagocytosis. Electron microscopy of PMN also indicated that the presence of hydrocortisone had no effect on the extent of degranulation after phagocytosis. These observations were confirmed by studies using histochemical techniques to detect lysosomal enzymes. After phagocytosis, hydrocortisone-treated PMN demonstrated less NADH oxidase activity, oxygen consumption, and hydrogen peroxide production than postphagocytic control PMN. In addition, Nitro blue tetrazolium dye reduction was diminished in hydrocortisone-treated PMN.Thus, impairment of NADH oxidase activity in normal human PMN by hydrocortisone results in reduced intracellular killing of bacteria, diminished postphagocytic oxygen consumption, decreased ability to reduce Nitro blue tetrazolium, and decreased hydrogen peroxide production. These abnormalities are similar to those seen in the PMN of patients with chronic granulomatous disease of childhood.
Significant Changes in Mitral Valve Leaflet Matrix Composition and Turnover With Tachycardia-Induced Cardiomyopathy
Authors: Elizabeth H. Stephens, Tomasz A. Timek, George T. Daughters, Joyce J. Kuo, Aaron M. Patton, L. Scott Baggett, Neil B. Ingels, D. Craig Miller, K. Jane Grande-Allen
Journal: Circulation (2009)

Dilated cardiomyopathy (DCM) involves significant remodeling of the left ventricular-mitral valve (MV) complex, but little is known regarding the remodeling of the mitral leaflets. The aim of this study was to assess changes in matrix composition and turnover in MV leaflets with DCM.Radiopaque markers were implanted in 24 sheep to delineate the MV; 10 sheep underwent tachycardia-induced cardiomyopathy (TIC), whereas 14 sheep remained as controls. Biplane videofluoroscopy was performed before and after TIC. Immunohistochemistry was performed on leaflet cross-sections taken from the septal, lateral, anterior, and posterior commissures attachment segments. Staining intensity was quantified within each attachment segment and leaflet region (basal, mid-leaflet, and free edge). Mitral regurgitation increased from 0.2+/-0.4 before TIC to 2.2+/-0.9 after TIC (P<0.0002). TIC leaflets demonstrated significant remodeling compared to controls, including greater cell density and loss of leaflet layered structure (all P<0.05). Collagen and elastic fiber turnover was greater in TIC, as was the myofibroblast phenotype (all P<0.05). Compositional differences between TIC and control leaflets were heterogeneous by annular segment and leaflet region, and related to regional changes in leaflet segment length with TIC.This study shows that the MV leaflets are significantly remodeled in DCM with changes in leaflet composition, structure, and valve cell phenotype. Understanding how alterations in leaflet mechanics, such as those induced by DCM, drive cell-mediated remodeling of the extracellular matrix will be important in developing future treatment strategies.
Barriers to concordance with antidiabetic drugs—cultural differences or human nature?
Authors: Trisha Greenhalgh
Journal: BMJ (2005)

British Indian and British Pakistani patients think that the products of the pharmaceutical industry are potent and may do harm. They do not want to take any more tablets than they absolutely have to. They discontinue their tablets if they have major side effects. They distrust doctors who stand to gain financially from prescribing particular drugs. They use creative strategies to titrate the dose of their drugs to the lowest that they consider works.1 In all these respects, the sample reported here has more similarities to than differences from the indigenous British population, and indeed most other groups studied in relation to medicine taking.2 3

That said, this study is no less …
Modification of atrioventricular node transmission properties by intraoperative neodymium-YAG laser photocoagulation in dogs
Authors: Laszlo Littmann, Robert H. Svenson, Istvan Tomcsanyi, Christoph Hehrlein, John J. Gallagher, Saroja Bharati, Maurice Lev, Robert Splinter, George P. Tatsis, Jan R. Tuntelder
Journal: Journal of the American College of Cardiology (1991)
THE PRESENT CONCEPTION OF THE PERIRENAL FASCIAAND ITS RÔLE IN FIXATION OF THE KIDNEY.
Authors: D. D. LEWIS
Journal: JAMA (1904)

The introduction of cross sections into anatomic work has simplified to a marked degree the study of the fasciae of the different regions of the body, and as a result we have at the present time accurate accounts of their osteal, muscular, vascular and visceral relations. Those fascias which are of the greatest surgical importance have received the greatest amount of attention, and the descriptions given of the cervical, axillary and pelvic fasciae are fairly uniform. The fascia surrounding the kidney has not received the amount of attention that it deserves, and in the majority of text-books on anatomy and surgery no mention is made of it. In monographs devoted to renal anatomy and surgery, considerable space is given to the description of this fascia and the rôle that it plays in kidney fixation, but many who are interested in kidney work do not have access to these works, and
Acetaminophen-induced fulminant hepatic failure in Dogs
Authors: L. Ortega, J. I. Landa Garcia, A. Torres Garcia, G. Silecchia, J. Arenas, A. Suarez, M. Moreno Azcoitia, J. Sanz Esponera, E. Moreno Gonzalez, J. L. Balibrea Cantero
Journal: Hepatology (1985)

Results concerning morphological and biochemical changes following intravenous administration of different doses of acetaminophen in dogs are reported. Acetaminophen infusion, as a parenteral solution (500 mg per kg per 90 min), produced fulminant hepatitis characterized by a good correlation between Portmann's grade of lesion and percentage of necrosis. All animals died within 76 hr after intoxication. Analysis of biochemical parameters revealed positive correlation between serum bilirubin levels and severity of the hepatic lesion. The experimental model of acetaminophen-induced hepatotoxicity is proposed as a model for evaluation of the therapeutic efficacy of new medical and surgical procedures.
Amelioration of Sickle Cell Disease by Persistent Fetal Hemoglobin
Authors: John F. Jackson
Journal: JAMA (1961)

THE CLINICAL manifestations of sickle cell anemia are thought to be due to the abnormal hemoglobin in the erythrocytes. In addition to Hemoglobin S, however, the erythrocytes of patients with sickle cell anemia may also contain fetal hemoglobin.<sup>1</sup>Since sickling of erythrocytes is decreased by fetal hemoglobin,<sup>2</sup>this study was undertaken to evaluate the effect of persistence of significant amounts of fetal hemoglobin on the clinical severity of the manifestations of sickle cell anemia. <h3>Materials and Methods</h3> Hemoglobin electrophoresis was performed on the red cell hemolysates of all University of Mississippi Medical Center patients suspected of having sickle cell anemia or trait. The filter paper electrophoresis technique of Motulsky et al.<sup>3</sup>was used. This method was modified by decreasing the voltage from 260 to 120 and increasing the duration of electrophoresis run from 5 to 23 hours, thereby achieving a greater spread of resulting components. Fetal
The Waiting Room
Authors: Mark S. Litwin
Journal: JAMA (1985)

The intensive care unit (ICU) waiting room is a dismal place. Patients' relatives sit, waiting for the doctors to enter with hints of prognosis and wondering whether they are being candid or filtering out painful information. Families grope toward specific goals: "He'll recover; it's just a matter of time," or "She's dying; it would be better to get it over with." Bernida, a 24-year-old mother, entered the ICU in status epilepticus. The corticosteroids she took for her lupus had been discontinued two weeks earlier, when she developed an acute psychosis. As her mental state improved, her disease flared, and she exhibited signs of lupus cerebritis. Late one evening, she began to have unremitting seizures. Intravenous tranquilizers did not quiet her, so she was transferred to the ICU, her body confused by abnormal signals from her ailing brain. But she was young and otherwise healthy, so the prognosis was good. Her
THE EPIDEMIOLOGY AND OUTCOMES OF PERCUTANEOUS CORONARY INTERVENTION BEFORE HIGH RISK NON-CARDIAC SURGERY: INSIGHTS FROM THE BMC2 REGISTRY
Authors: Palaniappan Muthappan, Dean Smith, Herbert Aronow, Kim Eagle, David Wohns, James Fox, David Share, Hitinder Gurm
Journal: Journal of the American College of Cardiology (2012)
Who needs a doctor for IBS?
Authors: F CREED
Journal: Gut (1997)

See article on page 394 

On page 394, Talley and colleagues report the results of a population based study which attempted to explain health care seeking for irritable bowel syndrome (IBS). Of their sample, 13% had IBS by Manning criteria and of these 73% had sought medical care for abdominal pain or discomfort. Those who had and had not sought medical care were compared—severity and duration of the abdominal pain were independently associated with health care seeking but psychological status and history of childhood abuse were not.

 This finding may be surprising as previous work in the USA had concluded that symptoms of psychological distress are unrelated to IBS but related to health care seeking1 and this view is often quoted in the literature. Talley et al ’s study seems to contradict this finding. How does it compare with other research?

 Two careful studies used a diary to record bowel symptoms. Both found that abdominal pain and diarrhoea differentiated IBS consulters from non-consulters.2 3 In the study by Heaton et al , the likelihood of consulting a physician with IBS …
Decreased neural crest stem cell expansion is responsible for the conotruncal heart defects within the Splotch (Sp2H)/Pax3 mouse mutant
Authors: S Conway
Journal: Cardiovascular Research (2000)

Objective: Several mouse models of cardiac neural crest cell (NCC)-associated conotruncal heart defects exist, but the specific cellular and molecular defects within cardiac NCC morphogenesis remain largely unknown. Our objective was to investigate the underlying mechanisms resulting in outflow tract defects and why insufficient cardiac NCC reach the heart of the Splotch (Sp2H) mouse mutant embryo. Methods: For this study we used in vitro cell culture techniques, in vivo mouse–chick chimeras, BrdU cell proliferation labeling, TUNEL labeling to visualize apoptosis and the molecular markers AP-2, Wnt-1 and Wnt-3a to characterize NCC morphogenesis in vivo. Results: Expression of the NCC marker AP-2 revealed an extensive reduction in migratory NCC, however the rates of cell proliferation and apoptosis were unaffected, and do not account for the Sp2H NCC-associated heart defects. Further expression analysis revealed that Wnt-1, but not Wnt-3a, is expressed at decreased levels within Sp2H and that the cardiac NCC fail to undergo normal NC stem cell proliferative expansion prior to migration while still in the neural folds. However, when placed into a wild-type matrix or a tissue culture environment, the Sp2H cardiac NCC could migrate normally. Additionally, this reduced population of Sp2H NC stem cells do migrate properly within the Sp2H environment, as observed by neurofilament expression and cardiac innervation. Conclusions:. Taken together, all these data indicate that the Sp2H defect is intrinsic to the NC stem cells themselves and that there is a decrease in the number of pre-migratory cardiac NCC that form. It appears that this decrease in NCC number is the primary defect that ultimately leads to a lack of a cardiac NCC-derived Sp2H outflow tract septum.
Reactions to BCG
Authors: P. W. A. Mansell
Journal: JAMA (1973)

<h3>To the Editor.—</h3> The Bacillus Calmette-Guérin (BCG) vaccine has been used as an anticancer agent at this center for a number of years, sometimes with excellent results.<sup>1 -3</sup>During the last few months a more extensive program has been undertaken, and we think that it is imperative at this stage to point out that BCG may provoke serious side effects. This agent is being widely used in the treatment of malignant disease by practitioners, some of whom may not be aware of it's toxicity and may not have adequate facilities to recognize and deal with untoward side effects. We are using either the Glaxo (Glaxo, USA) or the TICE strain (Chicago Research Foundation) and have encountered two reactions, the most severe of which followed the use of the latter agent. In the first type, pyrexia, often as high as 40 C (104 F) accompanied malaise, vomiting, arthralgia, and headache.
Regulation of CXCR4 by the Notch Ligand Delta-like 4 in Endothelial Cells
Authors: Cassin Kimmel Williams, Marta Segarra, Maria De La Luz Sierra, Richard C.A. Sainson, Giovanna Tosato, Adrian L. Harris
Journal: Cancer Research (2008)

Abstract Gene-targeting studies have shown that Delta-like 4 (Dll4) is required for normal embryonic vascular remodeling, but the mechanisms underlying Dll4 regulatory functions are not well defined. We generated primary human umbilical vascular endothelial cells that express Dll4 protein to study Dll4 function and previously showed that Dll4 down-regulates vascular endothelial growth factor (VEGF) receptor 2 and NRP1 expression and inhibits VEGF function. We now report that expression of Dll4 in endothelial cells inhibited attachment and migration to stromal-derived growth factor 1 (SDF1) chemokine. Cell surface, total protein, and mRNA levels of CXCR4, principal signaling receptor for SDF1, were significantly decreased in Dll4-transduced endothelial cells, attributable to a significant reduction of CXCR4 promoter activity. An immobilized recombinant extracellular portion of Dll4 (rhDLL4) was sufficient to down-regulate CXCR4 mRNA and protein, whereas protein levels of SDF1, VEGF, and RDC1 were unchanged. The γ-secretase inhibitor L-685,458 significantly reconstituted CXCR4 mRNA in rhDLL4-stimulated endothelial cells. CXCR4 mRNA levels were significantly reduced in mouse xenografts of Dll4-transduced human gliomas compared with control gliomas, and vascular CXCR4 was not detected by immunohistochemistry in the enlarged vessels within the Dll4 gliomas. Thus, Dll4 may contribute to vascular differentiation and inhibition of the angiogenic response by regulating multiple receptor pathways. [Cancer Res 2008;68(6):1889–95]
Position of power
Authors: Ruth Williams
Journal: The Journal of Experimental Medicine (2006)

Migrating leukocytes are “rear-wheel drive cells,” says Antonella Viola. Her group finds that mitochondria, the cell's engines, shift to the back of neutrophils to power cell movement, as revealed in Campello et al. (page 2879).






Figure 1

A migrating leukocyte gets its rear in gear by shifting mitochondia (red) to its back end.




Mitochondria can accumulate in regions of the cell with high energy demands, such as at the active growth cones of developing neurons and at the neuromuscular synapse. Viola and her team wondered whether mitochondria might also adopt a specific intracellular location in migrating cells. Leukocytes migrate to immunological battlegrounds in response to chemokines, and the team now shows that, in vitro, this chemotaxis is coupled with movement of mitochondria to the rear of the cell, known as the uropod.

Although the leading edge of the leukocyte sends out exploratory protrusions as these cells migrate, the uropod contains both the adhesion machinery and the myosin motors essential for cell movement, explains Viola. The discovery that mitochondria also relocate to the uropod leads Viola to suggest that, in the mechanics of cell migration, the power comes from the push.

Mitochondrial movement along microtubules requires the mitochondria to first divide into smaller, mobile units. By preventing this division, the team revealed that mitochondrial relocation to the uropod was not just coupled with, but necessary for, leukocyte migration.

Boosting the mitochondrial energy production in these cells compensated for a lack of relocation, suggesting that mitochondrial movement was required for localizing ATP production at the uropod. Indeed, the team showed that inhibiting mitochondrial, but not cytoplasmic ATP production, reduced activation of myosin motors in the uropod but not elsewhere in the cell.

In addition to various leukocytic cell types, migrating human breast cancer cells also relocate their mitochondria to the rear, the team found. This suggests that inhibiting the division of mitochondria, and thus their movement, might be a potential intervention strategy for preventing tumor metastasis.
Abstract 3203: High quality DNA obtained with an automated DNA Extraction method with 15 to 40 year old formalin fixed paraffin embedded (FFPE) blocks from normal and cancer tissues
Authors: Erin Niland, Audrey D. McGuire, Mary L. Cox, George E. Sandusky
Journal: Cancer Research (2012)

Abstract DNA and RNA have been used as markers of tissue quality and integrity in tissues the last decade. In this research study, kidney, liver, colon, lung, and breast genomic quality were analyzed in tissues from surgical cancer patients and post-mortem cases obtained with an IRB approved protocol and informed/or next of kin consent. DNA extraction was performed on formalin-fixed paraffin-embedded tissues (FFPE) from both groups of cases from the 1970's through the 2000's and formalin fixed / long term 70% ethanol storage(15 + years). To extract the DNA from the FFPE tissues, we soaked all tissues in xylene to remove the paraffin, digested the tissue with a proteinase K solution, and used an automated extraction machine to extract the DNA. A similar SOP was used for the formalin fixed/ 70% long term ethanol-stored tissue, except the tissue was first homogenized rather than soaked in xylene. DNA quality and yield were evaluated using a spectrophotometer. Gel electrophoresis was used to evaluate the length of the DNA in about 20% of the 200 samples. Samples that had optical density (OD) readings above 1.60 and below 2.10 with a DNA yield above 100 µg/mL were deemed to be high quality DNA. FFPE tissues yielded the highest DNA concentration and quality (OD reading of 1.87 and yield of 625 ug/ml) with greater than 95% of the samples meeting the above specifications, while the formalin fixed/long term 70% ethanol stored tissue yielded both the lowest DNA concentration and quality (yield of 52 ug/ml and OD reading of 1.48). In conclusion, the results show that high quality DNA can be extracted from FFPE tissue using an automated DNA extraction procedure with paraffin blocks from the early 1970's to present, and the DNA extracted is useful for clinical and experimental studies. The DNA from tissues stored in aqueous media (formalin fixed / long term 70% ethanol storage) may be useful in some research applications, but the DNA is partially degraded compared to the tissue stored in paraffin blocks. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3203. doi:1538-7445.AM2012-3203
Nonvalvular Infections of the Cardiovascular System
Authors: Rosemary A. Kearney
Journal: Annals of Internal Medicine (1994)

Purpose: To review the risk factors, clinical presentation, diagnosis, and treatment of nonvalvular infections of the cardiovascular system. Data Sources: A MEDLINE search of English-language articles from 1966 to 1993 relating to myocardial abscesses, mural endocarditis, infective endarteritis and mycotic aneurysms, infection of pacemakers and implantable defibrillators, prosthetic vascular graft infections, and infected atrial myxomas; manual review of article bibliographies. Study Selection and Data Extraction: Case series and single reports, prospective and retrospective clinical studies, autopsy studies, and reviews were selected if they contained sufficient information about the prevalence, clinical manifestations, microbiologic features, management, and outcome of nonvalvular cardiovascular infections. Results: Nonvalvular infections of the cardiovascular system most commonly occur on previously damaged endocardium or vascular intima and are usually associated with intravascular devices such as graft material or pacemakers. Rarely, they can involve primary cardiac tumors such as myxomas. Most patients affected are beyond the fifth decade of life. Risk factors include cardiovascular disease, diabetes mellitus, and malignancy. The sexes are affected equally. The clinical presentations of nonvalvular endovascular infections are subtle and diagnoses are difficult to make, often requiring not only a high index of suspicion but also the use of sophisticated radiologic techniques. Hence, for many of these infections, the diagnosis is made late in the course of the infection, and survival rates are poor. Complications include peripheral embolization, cardiac rupture, vascular aneurysm rupture, and pericarditis. Therapy frequently involves surgical intervention in addition to the use of antibiotics. Conclusions: Although uncommon, nonvalvular infections of the cardiovascular system will increase in frequency as the use of implantable devices and prosthetic materials increases in the elderly. Studies are needed to determine the most appropriate diagnostic methods, treatment regimens, and methods for prevention of these infections.