tbuckley/cabot-search huggingface dataset:
Developmental Expression of Protein Phosphatase 2A in the Kidney
Authors: ALLEN D. EVERETT, CHUN XUE, TAMARA STOOPS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Although a number of growth and transcription factors are known to regulate renal growth and development, the signal transduction molecules necessary to mediate these developmental signals are relatively unknown. Therefore, the activity and mRNA and protein expression of the signal transduction molecule protein phosphatase 2A (PP2A) were examined during rat kidney development. Northern analysis of total kidney RNA or Western analysis of kidney protein homogenates from embryonic day 15 to 90-d-old adults demonstrated developmental regulation of the catalytic, major 55-kD B regulatory subunit and A structural subunit with the highest levels of expression in late embryonic and newborn kidneys. Similarly, okadaic acid-inhibitable phosphatase enzyme activity was highest in the embryonic and newborn kidney. To map cell-specific expression of PP2A in the developing kidney, in situ hybridization with a catalytic subunit digoxigenin-labeled cRNA was performed on embryonic day 20 and newborn kidneys. PP2A was found predominately in the nephrogenic cortex and particularly in the developing glomeruli and nonbrush border tubules in the embryonic day 20 and newborn kidneys. Similarly, immunocytochemistry with a specific PP2A catalytic subunit polyclonal anti-peptide antibody demonstrated catalytic subunit protein particularly concentrated in the podocytes of glomeruli in the newborn kidney. In the adult kidney, PP2A protein was no longer detectable except in the nuclei of distal tubular cells. Therefore, the developmental regulation of PP2A activity and protein during kidney development and its mapping to the nephrogenic cortex, developing glomeruli, and tubules suggests a role for PP2A in the regulation of nephron growth and differentiation.
Association Between Metformin Use and Risk of Prostate Cancer and Its Grade
Authors: David Margel, David Urbach, Lorraine L. Lipscombe, Chaim M. Bell, Girish Kulkarni, Peter C. Austin, Neil Fleshner
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundMetformin is commonly prescribed to treat type 2 diabetes. Recent evidence suggests that it may possess antitumoral properties. The aim of this study was to test the association between metformin use and risk of prostate cancer and its grade among men with diabetes.
Novel IL33 Gene Polymorphisms Associated with Asthma Are Associated with Resistance to Schistosoma Mansoni
Authors: Hironori Masuko, Li Gao, Nicholas M. Rafaels, Candelaria I. Vergara, Lili Huang, Monica Campbell, Ingo Ruczinski, Terri H. Beaty, Ricardo Oliveira, Alvaro A. Cruz, Edgar M. Carvalho, Rasika A. Mathias, Maria Ilma Araujo, Kathleen C. Barnes
Journal: Journal of Allergy and Clinical Immunology (2013)
Serodiagnosis and Monitoring of Aspergillus Infections after Lung Transplantation
Authors: J.F. Chris Tomee
Journal: Annals of Internal Medicine (1996)

To determine whether quantification of specific antifungal antibody responses in serum can provide supplemental information for the diagnosis of Aspergillus fumigatus infections and the monitoring of antifungal treatment in patients after lung transplantation.Retrospective study.Center for lung transplantation, University Hospital Groningen, the Netherlands.4 patients with proven A. fumigatus infections after lung transplantation and fatal outcome.The IgG antibody response specific for A. fumigatus antigens was measured by enzyme-linked immunosorbent assay and was compared with radiographic features, cytologic findings, microbiological cultures, and clinical diagnosis.Increasing IgG antibody responses specific for A. fumigatus antigens closely paralleled cytologic or microbiological identification of A. fumigatus from bronchoalveolar lavage fluid and decrease of lung function. Increasing specific IgG antibody responses were found to precede radiographic identification of lung cavitation by 1 to 2 weeks, precede the diagnosis of aspergillosis by 2 to 20 weeks, and detect fungal reinfection. In most cases, successful antifungal treatment decreased specific IgG antibody response. A decrease in specific IgG antibody response correlated with the inability to culture or identify A. fumigatus in bronchoalveolar lavage fluid and with radiographic and clinical improvement.Specific IgG antibody responses in serum correlate with radiographic, cytologic, and microbiological findings and with the clinical diagnosis of A. fumigatus infections in patients who have had lung transplantation. Increased IgG antibody responses in serum may provide important information that is helpful in the diagnosis and early treatment of pulmonary fungal infections and in monitoring antifungal treatment.
Simulation Study of Cellular Electric Properties in Heart Failure
Authors: Leo Priebe, Dirk J. Beuckelmann
Journal: Circulation Research (1998)

Abstract —Patients with severe heart failure are at high risk of sudden cardiac death. In the majority of these patients, sudden cardiac death is thought to be due to ventricular tachyarrhythmias. Alterations of the electric properties of single myocytes in heart failure may favor the occurrence of ventricular arrhythmias in these patients by inducing early or delayed afterdepolarizations. Mathematical models of the cellular action potential and its underlying ionic currents could help to elucidate possible arrhythmogenic mechanisms on a cellular level. In the present study, selected ionic currents based on human data are incorporated into a model of the ventricular action potential for the purpose of studying the cellular electrophysiological consequences of heart failure. Ionic currents that are not yet sufficiently characterized in human ventricular myocytes are adopted from the action potential model developed by Luo and Rudy (LR model). The main results obtained from this model are as follows: The action potential in ventricular myocytes from failing hearts is longer than in nonfailing control hearts. The major underlying mechanisms for this prolongation are the enhanced activity of the Na + -Ca 2+ exchanger, the slowed diastolic decay of the [Ca 2+ ] i transient, and the reduction of the inwardly rectifying K + current and the Na + -K + pump current in myocytes of failing hearts. Furthermore, the fast and slow components of the delayed rectifier K + current ( I Kr and I Ks , respectively) are of utmost importance in determining repolarization of the human ventricular action potential. In contrast, the influence of the transient outward K + current on APD is only small in both cell groups. Inhibition of I Kr promotes the development of early afterdepolarizations in failing, but not nonfailing, myocytes. Furthermore, spontaneous Ca 2+ release from the sarcoplasmic reticulum triggers a premature action potential only in failing myocytes. This model of the ventricular action potential and its alterations in heart failure is intended to serve as a tool for investigating the effects of therapeutic interventions on the electric excitability of the human ventricular myocardium.
Mesothelin and osteopontin
Authors: Gunnar Hillerdal
Journal: European Respiratory Journal (2013)

The review by PANTAZOPOULOS et al. [1] on mesothelin and osteopontin was timely and well written.However, I would like to comment on some of the statements that were made.Firstly, it states that ''patients with early-stage disease can survive for more than 5 years if the tumour is promptly resected''.This implies that resection would benefit the patient, which is far from proven; there is no randomised study showing this, except for the much criticised the Mesothelioma and Radical Surgery (MARS) study [2] in England, which showed that resection considerably shortened survival.The good survival seen by SUGARBAKER et al.[3] and in other studies can be explained by very strict selection and these patients are likely to survive at least as long without resection, as seen from studies where ''operable'' patients were treated conservatively.Furthermore, the authors claim that ''early diagnosis offers the best hope for a favourable prognosis'', which is an interesting but unproven hypothesis.There is of course a lead time bias, the earlier the diagnosis the longer the survival, but unfortunately we do not know whether early intervention will in fact prolong survival.Thus, screening for mesothelioma in risk groups is not indicated at present, screening should only be performed in diseases where the prognosis has been shown to be improved by early discovery.I fully agree with the other main conclusions in the review, namely that mesothelin, in serum or pleura, can be a useful aid in the diagnostic setup and also used for monitoring patients for recurrence.
2 integrins control the proinflammatory phenotype of type 1 macrophages and dendritic cells
Authors: M. H. Wenink, K. C. M. Santegoets, R. Huijbens, L. van Bon, C. Volgers, M. Weenk, P. L. C. M. van Riel, W. B. van den Berg, T. R. D. J. Radstake
Journal: Annals of the Rheumatic Diseases (2010)

The authors hypothesised that the accumulation of macrophages at a site of inflammation induces a shift from an initially proinflammatory macrophage phenotype to a phenotype aimed at suppressing the initiated immune response when sufficient numbers of macrophages have been recruited. To investigate this, the authors cultured monocytes with granulocyte-macrophage colony forming units or macrophage colony forming units into proinflammatory type …
Personal genotypes are teachable moments
Authors: Mark S Boguski, Robert M Boguski, Michele R Berman
Journal: Genome Medicine (2013)

There is an urgent need for effective genomics education for healthcare professionals. Recent analysis of an experimental genomics curriculum showed that medical students' examinations of their own genotypes provide a valuable learning experience. Such experiential learning has a long tradition in medical education and its application to genomics is enabled by increasingly powerful and decreasingly costly genome science and technology. Personal genotyping is an important option to consider when designing educational programs for healthcare professionals.
Hematopoietic stem cell transplantation for de novo acute megakaryocytic leukemia in first complete remission: a retrospective study of the European Group for Blood and Marrow Transplantation (EBMT)
Authors: Laurent Garderet, Myriam Labopin, Norbert-Claude Gorin, Emmanuelle Polge, André Baruchel, Giovanna Meloni, Juan Ortega, Jaak Vossen, Donald Bunjes, Guy Leverger, Didier Blaise, Augustin Ferrant, Mats Brune, Eric Dore, Helmut Gadner, Felix Zintl, Isaac Yaniv, Giorgio Dini, Francesco Frassoni
Journal: Blood (2004)
CLINICAL FINDINGS AND SEROLOGICAL EVIDENCE OF HTLV-III INFECTION IN HOMOSEXUAL CONTACTS OF PATIENTS WITH AIDS AND PERSISTENT GENERALISED LYMPHADENOPATHY IN LONDON
Authors: B.G. Gazzard, C. Farthing, D.C. Shanson, A.G. Lawrence, R.S. Tedder, R. Cheingsong-Popov, A. Dalgleish, R.A. Weiss
Journal: The Lancet (1984)
Comparison of relapse rates and of mucosal abnormalities after healing of duodenal ulceration and after one year's maintenance with cimetidine or sucralfate: a light and electron microscopy study.
Authors: F I Tovey, E M Husband, Y C Yiu, L Baker, G McPhail, M R Lewin, A P Jayaraj, C G Clark
Journal: Gut (1989)

Forty six patients with endoscopically diagnosed duodenal ulceration were randomly allocated to treatment with either sucralfate 1 g qds (n = 24) or cimetidine 200 mg tds and 400 mg nocte (n = 22). When the ulcers healed, a maintenance dose of sucralfate 1 g bd or cimetidine 400 mg nocte was given for one year (or until relapse if earlier). Biopsies of duodenal mucosa adjacent to ulcer sites for light and electron microscopy were obtained before and after healing and again after one year's maintenance if the ulcer remained healed. Duodenal biopsies were also taken from 20 age and sex matched controls. Rates of healing and relapse during maintenance did not differ between the two treatments, although relapses occurred earlier with cimetidine. In the three year post-maintenance follow up period 10/13 cimetidine patients relapsed compared with four of 11 sucralfate patients (p less than 0.05), the relapses occurring significantly earlier in the cimetidine treated patients (p less than 0.05). Mucosal biopsies from both treatment groups still showed considerable abnormalities after healing. During maintenance, however, the sucralfate scores fell significantly (p less than 0.02) to near control levels unlike the cimetidine scores which remained raised at pretreatment values. The histological and ultrastructural changes were not predictive of later relapse. These findings favour the use of sucralfate in preference to cimetidine for maintenance treatment in the prevention of relapse of healed duodenal ulcers.
Audit of a new mannitol challenge testing service in a UK tertiary centre
Authors: Martyn Bucknall
Journal: European Respiratory Journal (2011)

Guys and St Thomas9 NHS Foundation trust (GSTT) is a tertiary hospital based in London, UK, offering specialist allergy and asthma clinics.  In July 2010, GSTT switched from using histamine to mannitol for performing bronchial challenge testing (BCT). BCT is an essential diagnostic investigation for identifying/excluding asthma and monitoring responses to treatment regiimes.  We performed an audit of the new service, using mannitol between July 2010 and February 2011. We looked at patient demographics, (age, sex, baseline lung function), test outcomes (i.e. positive, negative, reasons for terminating test, fall in FEV1), sources of referral and clinical rweasons for referral to our laboratory.  Table 1 shows patient demographics and baseline lung function. 60 patients were referred to the service (28M, 32F). The mean age was 40.2 yrs.  Table 2 shows source of referral and reason for referral.
ENHANCED PASSIVE IMMUNITY TO STREPTOCOCCUS INFECTION IN RABBITS
Authors: F. P. Gay, A. R. Clark
Journal: The Journal of Experimental Medicine (1930)

The experimental work herein reported tends to justify our hypothesis recently expressed, that the common failure of antibacterial serums to combat active infections when passively transferred to a normal animal, is due not so much to a lack of suitable or sufficient antibodies as to absence of cell preparation or mobilization in the recipient. In the case of experimental streptococcus empyema in the rabbit the course of the ordinarily fatal infection is in no wise affected by the transfer of the pleural fluid containing large numbers of mononuclear cells derived from an animal that is itself protected as a result of a non-specific irritation. The serum of a rabbit highly immunized against the streptococcus and containing antibodies for it, produces relatively slight effect in prevention or cure. In contrast to this the pleural exudate, either acute (polymorphonuclear) or subacute (mononuclear), produced in an actively immunized animal does protect passively to a considerable degree. In a similar fashion normal exudate cells of either type in combination with the relatively ineffective antiserum give a high degree of protection. It remains for further analysis to determine whether this form of passive immunity by antiserum enhanced by the addition of cells depends on the vital properties of the cells transferred or on their stimulation to cell mobilization in the recipient. And furthermore the extent to which this enhanced passive immunity may be effective in cure, and whether the cure is applicable to local or to both local and generalized infection remains to be seen.
Quality of Life and Outcomes in African Americans with CKD
Authors: Anna Porter, Michael J. Fischer, Xuelei Wang, Deborah Brooks, Marino Bruce, Jeanne Charleston, William H. Cleveland, Donna Dowie, Marquetta Faulkner, Jennifer Gassman, Leena Hiremath, Cindy Kendrick, John W. Kusek, Keith C. Norris, Denyse Thornley-Brown, Tom Greene, James P. Lash
Journal: Journal of the American Society of Nephrology (2014)

Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies. Outcomes included CKD progression (doubling of serum creatinine/ESRD), CV events/CV death, and a composite of CKD progression or death from any cause (CKD progression/death). We assessed HRQOL, including mental health composite (MHC) and physical health composite (PHC), using the Short Form-36 survey. Cox regression analyses were used to assess the relationship between outcomes and five-point decrements in MHC and PHC scores using measurements at baseline, at the most recent annual visit (time-varying), or averaged from baseline to the most recent visit (cumulative). During approximately 10 years of follow-up, lower mean PHC score was associated with increased risk of CV events/CV death and CKD progression/death across all analytic approaches, but only time-varying and cumulative decrements were associated with CKD progression. Similarly, lower mean MHC score was associated with increased risk of CV events/CV death regardless of analytic approach, while only time-varying and cumulative decrements in mean MHC score was associated with CKD progression and CKD progression or death. In conclusion, lower HRQOL is associated with a range of adverse outcomes in African Americans with hypertensive CKD.
Alterations in upper airway cross-sectional area in response to lower body positive pressure in healthy subjects
Authors: S. Shiota, C. M Ryan, K.-L. Chiu, P. Ruttanaumpawan, J. Haight, M. Arzt, J. S Floras, C. Chan, T D. Bradley
Journal: Thorax (2007)

<b>Background:</b> Fluid accumulation in the neck during recumbency might narrow the upper airway (UA) and thereby contribute to its collapse in patients with obstructive sleep apnoea (OSA). It is hypothesised that acute fluid shifts from the legs to the upper body in healthy subjects would increase neck circumference and reduce the cross-sectional area of the UA (UA-XSA). <b>Methods:</b> In 27 healthy non-obese subjects of mean (SE) age 39 (3) years and body mass index 23.2 (0.6) kg/m<sup>2</sup> studied while supine, leg fluid volume was measured using bioelectrical impedance, neck circumference using a mercury strain gauge and mean UA-XSA between the velum and the glottis using acoustic pharyngometry at end expiration. Measurements were made at baseline after which subjects were randomly assigned to a 5 min time control period or to a 5 min application of lower body positive pressure (LBPP) at 40 mm Hg by anti-shock trousers, separated by a 15 min washout period. Subjects then crossed over to the opposite arm of the study. <b>Results:</b> Compared with control, application of LBPP significantly reduced leg fluid volume (p&lt;0.001) and increased neck circumference (p&lt;0.001), both at 1 min and 5 min, and reduced UA-XSA after both 1 min (−0.15 cm<sup>2</sup>; 95% CI −0.23 to −0.09, p&lt;0.001) and 5 min (−0.20 cm<sup>2</sup>; 95% CI −0.33 to −0.09, p&lt;0.001). <b>Conclusion:</b> In healthy subjects, displacement of fluid from the legs by LBPP causes distension of the neck and narrowing of the UA lumen. Fluid displacement from the lower to the upper body while recumbent may contribute to pharyngeal narrowing and obstruction to airflow in patients with OSA. This may have particular pathological significance in oedematous states such as heart and renal failure.
45 IMMUNE EVASION OF HEPATITIS DELTA FROM CD8+ T CELL IMMUNE RESPONSE
Authors: H. Karimzadeh, A. Kosinska, B. Budeus, M. Fiedler, M. Homs, A. Olivero, M. Buti, H. Keyvani, F. Rodríguez Frías, S.M. Alavian, D. Hoffmann, A. Smedile, M. Rizzetto, H. Wedemeyer, J. Timm, M. Roggendorf
Journal: Journal of Hepatology (2013)
Mechanisms of non-contact ACL injuries
Authors: Bing Yu, William E Garrett
Journal: British Journal of Sports Medicine (2007)

In soccer one of the most common knee injuries is the anterior cruciate ligament (ACL) tear, which usually occurs through non-contact mechanisms. Female soccer players are at higher risk of sustaining non-contact ACL injuries than male soccer players. A good understanding of ACL loading mechanisms is the basis for a good understanding of the mechanisms of non-contact ACL injuries, which in turn is essential for identifying risk factors and developing prevention strategies. Current literature demonstrates that sagittal plane biomechanical factors, such as small knee flexion angle, great posterior ground reaction force and great quadriceps muscle force, are the major ACL loading mechanisms. A great posterior ground reaction force may be associated with a great quadriceps muscle force, which would cause great anterior draw force at the knee. A small knee flexion is associated with a large patella tendon-tibia shaft angle and ACL elevation angle, which would result in great ACL loading. Current literature also demonstrates that the ACL is not the major structure of bearing knee valgus-varus moment and internal-external rotation loadings. Knee valgus-varus moment and internal-external rotation moment alone are not likely to result in isolated ACL injuries without injuring other knee structures.
Classification and Prediction of Survival in Patients with the Leukemic Phase of Cutaneous T Cell Lymphoma
Authors: Laszlo Kari, Andrey Loboda, Michael Nebozhyn, Alain H. Rook, Eric C. Vonderheid, Calen Nichols, Dezso Virok, Celia Chang, Wen-Hwai Horng, James Johnston, Maria Wysocka, Michael K. Showe, Louise C. Showe
Journal: The Journal of Experimental Medicine (2003)

We have used cDNA arrays to investigate gene expression patterns in peripheral blood mononuclear cells from patients with leukemic forms of cutaneous T cell lymphoma, primarily Sezary syndrome (SS). When expression data for patients with high blood tumor burden (Sezary cells &amp;gt;60% of the lymphocytes) and healthy controls are compared by Student's t test, at P &amp;lt; 0.01, we find 385 genes to be differentially expressed. Highly overexpressed genes include Th2 cells–specific transcription factors Gata-3 and Jun B, as well as integrin β1, proteoglycan 2, the RhoB oncogene, and dual specificity phosphatase 1. Highly underexpressed genes include CD26, Stat-4, and the IL-1 receptors. Message for plastin-T, not normally expressed in lymphoid tissue, is detected only in patient samples and may provide a new marker for diagnosis. Using penalized discriminant analysis, we have identified a panel of eight genes that can distinguish SS in patients with as few as 5% circulating tumor cells. This suggests that, even in early disease, Sezary cells produce chemokines and cytokines that induce an expression profile in the peripheral blood distinctive to SS. Finally, we show that using 10 genes, we can identify a class of patients who will succumb within six months of sampling regardless of their tumor burden.