tbuckley/cabot-search huggingface dataset:
Recruitment of Podocytes from Glomerular Parietal Epithelial Cells
Authors: Daniel Appel, David B. Kershaw, Bart Smeets, Gang Yuan, Astrid Fuss, Bjo[Combining Diaeresis] Frye, Marlies Elger, Wilhelm Kriz, Ju[Combining Diaeresis]rgen Floege, Marcus J. Moeller
Journal: Journal of the American Society of Nephrology (2008)

Loss of a critical number of podocytes from the glomerular tuft leads to glomerulosclerosis. Even in health, some podocytes are lost into the urine. Because podocytes themselves cannot regenerate, we postulated that glomerular parietal epithelial cells (PECs), which proliferate throughout life and adjoin podocytes, may migrate to the glomerular tuft and differentiate into podocytes. Here, we describe transitional cells at the glomerular vascular stalk that exhibit features of both PECs and podocytes. Metabolic labeling in juvenile rats suggested that PECs migrate to become podocytes. To prove this, we generated triple-transgenic mice that allowed specific and irreversible labeling of PECs upon administration of doxycycline. PECs were followed in juvenile mice beginning from either postnatal day 5 or after nephrogenesis had ceased at postnatal day 10. In both cases, the number of genetically labeled cells increased over time. All genetically labeled cells coexpressed podocyte marker proteins. In conclusion, we demonstrate for the first time recruitment of podocytes from PECs in juvenile mice. Unraveling the mechanisms of PEC recruitment onto the glomerular tuft may lead to novel therapeutic approaches to renal injury.
T<scp>he</scp>R<scp>ole of</scp>S<scp>uppressors of</scp>C<scp>ytokine</scp>S<scp>ignaling</scp>(SOCS) P<scp>roteins in</scp>R<scp>egulation of the</scp>I<scp>mmune</scp>R<scp>esponse</scp>
Authors: Warren S. Alexander, Douglas J. Hilton
Journal: Annual Review of Immunology (2004)

Cytokines are an integral component of the adaptive and innate immune responses. The signaling pathways triggered by the engagement of cytokines with their specific cell surface receptors have been extensively studied and have provided a profound understanding of the intracellular machinery that translates exposure of cells to cytokine to a coordinated biological response. It has also become clear that cells have evolved sophisticated mechanisms to prevent excessive responses to cytokines. In this review we focus on the suppressors of cytokine signaling (SOCS) family of cytoplasmic proteins that completes a negative feedback loop to attenuate signal transduction from cytokines that act through the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. SOCS proteins inhibit components of the cytokine signaling cascade via direct binding or by preventing access to the signaling complex. The SOCS proteins also appear to target signal transducers for proteasomal destruction. Analyses of genetically modified mice in which SOCS proteins are overexpressed or deleted have established that this family of negative regulators has indispensable roles in regulating cytokine responses in cells of the immune system as well as other tissues. Emerging evidence also suggests that disruption of SOCS expression or activity is associated with several immune and inflammatory diseases, raising the prospect that manipulation of SOCS activity may provide a novel future therapeutic strategy in the management of immunological disorders.
Racial and Ethnic Disparities in the Quality of Health Care
Authors: Kevin Fiscella, Mechelle R. Sanders
Journal: Annual Review of Public Health (2015)

The annual National Healthcare Quality and Disparities Reports document widespread and persistent racial and ethnic disparities. These disparities result from complex interactions between patient factors related to social disadvantage, clinicians, and organizational and health care system factors. Separate and unequal systems of health care between states, between health care systems, and between clinicians constrain the resources that are available to meet the needs of disadvantaged groups, contribute to unequal outcomes, and reinforce implicit bias. Recent data suggest slow progress in many areas but have documented a few notable successes in eliminating these disparities. To eliminate these disparities, continued progress will require a collective national will to ensure health care equity through expanded health insurance coverage, support for primary care, and public accountability based on progress toward defined, time-limited objectives using evidence-based, sufficiently resourced, multilevel quality improvement strategies that engage patients, clinicians, health care organizations, and communities.
Integrating Psychosocial Care Into Cancer Services
Authors: Jesse R. Fann, Kathleen Ell, Michael Sharpe
Journal: Journal of Clinical Oncology (2012)

Despite substantial evidence that patients with cancer commonly have significant psychosocial problems, for which we have evidence-based treatments, many patients still do not receive adequate psychosocial care. This means that we risk prolonging life without adequately addressing the quality of that life. There are many challenges to improving the current situation, the major one of which is organizational. Many cancer centers lack a system of psychosocial care that is integrated with the cancer care of the patient. Psychosocial care encompasses a range of problems (emotional, social, palliative, and logistical). The integration must occur with the cancer care of the patient at all stages (from screening to palliative care) and across all clinical sites of care (inpatient and outpatient cancer services as well as primary care). In this article, we consider the challenges we face if we are to provide such integrated psychosocial services. We focus on the collaborative care service model. This model comprises systematic identification of need, integrated delivery of care by care managers, appropriate specialist supervision, and the stepping of care based on systematic measurement of outcomes. Several trials of this approach to the management of depression in patients with cancer have found it to be both feasible to deliver and effective. It provides a model for services to meet other psychosocial needs. We conclude by proposing the key components of an integrated psychosocial service that could be implemented now and by considering what we need to do next if we are to succeed in providing better and more comprehensive care to our patients.
Electrophysiological evaluation of the Wolff-Parkinson-White syndrome: problems in assessing antegrade and retrograde conduction over the accessory pathway.
Authors: R H Svenson, H C Miller, J J Gallagher, A G Wallace
Journal: Circulation (1975)

The effect of atrial pacing and recording site and ventricular pacing site on assessment of conduction over the accessory pathway (AP) was examined in a group of patients with the Wolff-Parkinson-White syndrome. The importance of initial localization of the AP by recording the sequence of retrograde atrial activation during circus movement tachycardia is demonstrated. Inability to record or pace near the AP may lead to significant errors in the assessment of the antegrade and retograde conduction properties of the AP. During ventricular pacing, retrograde atrial fusion was consistently demonstrated with laterally located APs.
Human Aortic Valve Calcification Is Associated With an Osteoblast Phenotype
Authors: Nalini M. Rajamannan, Malayannan Subramaniam, David Rickard, Stuart R. Stock, Janis Donovan, Margaret Springett, Thomas Orszulak, David A. Fullerton, A.J. Tajik, Robert O. Bonow, Thomas Spelsberg
Journal: Circulation (2003)

Calcific aortic stenosis is the third most common cardiovascular disease in the United States. We hypothesized that the mechanism for aortic valve calcification is similar to skeletal bone formation and that this process is mediated by an osteoblast-like phenotype.To test this hypothesis, we examined calcified human aortic valves replaced at surgery (n=22) and normal human valves (n=20) removed at time of cardiac transplantation. Contact microradiography and micro-computerized tomography were used to assess the 2-dimensional and 3-dimensional extent of mineralization. Mineralization borders were identified with von Kossa and Goldner's stains. Electron microscopy and energy-dispersive spectroscopy were performed for identification of bone ultrastructure and CaPO4 composition. To analyze for the osteoblast and bone markers, reverse transcriptase-polymerase chain reaction was performed on calcified versus normal human valves for osteopontin, bone sialoprotein, osteocalcin, alkaline phosphatase, and the osteoblast-specific transcription factor Cbfa1. Microradiography and micro-computerized tomography confirmed the presence of calcification in the valve. Special stains for hydroxyapatite and CaPO4 were positive in calcification margins. Electron microscopy identified mineralization, whereas energy-dispersive spectroscopy confirmed the presence of elemental CaPO4. Reverse transcriptase-polymerase chain reaction revealed increased mRNA levels of osteopontin, bone sialoprotein, osteocalcin, and Cbfa1 in the calcified valves. There was no change in alkaline phosphatase mRNA level but an increase in the protein expression in the diseased valves.These findings support the concept that aortic valve calcification is not a random degenerative process but an active regulated process associated with an osteoblast-like phenotype.
Ventricular mechanoreflex and chemoreflex alterations in chronic heart failure.
Authors: M Brändle, W Wang, I H Zucker
Journal: Circulation Research (1994)

Cardiac and arterial baroreflex control of the circulation is abnormal in both human and experimental heart failure. Ventricular vagal afferents mediate mechanical and chemical reflexes, which result in bradycardia and hypotension. The aim of the present study was to evaluate the changes that occur in ventricular mechanoreflexes and chemoreflexes in a conscious canine model of chronic heart failure. Dogs were instrumented for the measurement of left ventricular pressure, left atrial pressure, arterial pressure, and heart rate. Vascular occluders were placed on the ascending thoracic aorta, on the descending thoracic aorta, and on the thoracic inferior vena cava. A chronic left circumflex coronary artery catheter was also implanted. Finally, a pacing lead was secured to the left ventricular free wall. After recovery from surgery (10 to 14 days), the dogs were subjected to complete arterial baroreceptor denervation. The responses to vascular occlusions and intracoronary administration of prostacyclin (PGI2) were carried out before and after heart failure was induced by chronic cardiac pacing at 250 beats per minute. PGI2 was used as a chemical stimulus for ventricular afferents; ascending aortic occlusion was used as a mechanical stimulus. Before chronic pacing, ascending aortic occlusion resulted in a decrease in heart rate of 36.1 +/- 12.3 beats per minute (mean +/- SD, P &lt; .001). After heart failure was induced, the heart rate response to ascending aortic occlusion was almost completely abolished. The slope of the linear relation between pulse interval and left ventricular end-diastolic pressure was reduced by 90.5% from a control value of 11.3 +/- 6.9 ms/mm Hg after heart failure had been induced.(ABSTRACT TRUNCATED AT 250 WORDS)
Integration of Repulsive Guidance Cues Generates Avascular Zones That Shape Mammalian Blood Vessels
Authors: Stryder M. Meadows, Peter J. Fletcher, Carlos Moran, Ke Xu, Gera Neufeld, Sophie Chauvet, Fanny Mann, Paul A. Krieg, Ondine Cleaver
Journal: Circulation Research (2011)

Rationale: Positive signals, such as vascular endothelial growth factor, direct endothelial cells (ECs) to specific locations during blood vessel formation. Less is known about repulsive signal contribution to shaping vessels. Recently, “neuronal guidance cues” have been shown to influence EC behavior, particularly in directing sprouting angiogenesis by repelling ECs. However, their role during de novo blood vessel formation remains unexplored. Objective: To identify signals that guide and pattern the first mammalian blood vessels. Methods and Results: Using genetic mouse models, we show that blood vessels are sculpted through the generation of stereotyped avascular zones by EC-repulsive cues. We demonstrate that Semaphorin3E (Sema3E) is a key factor that shapes the paired dorsal aortae in mouse, as sema3E −/− embryos develop an abnormally branched aortic plexus with a markedly narrowed avascular midline. In vitro cultures and avian grafting experiments show strong repulsion of ECs by Sema3E-expressing cells. We further identify the mouse notochord as a rich source of multiple redundant neuronal guidance cues. Mouse embryos that lack notochords fail to form cohesive aortic vessels because of loss of the avascular midline, yet maintain lateral avascular zones. We demonstrate that lateral avascular zones are directly generated by the lateral plate mesoderm, a critical source of Sema3E. Conclusions: These findings demonstrate that Sema3E-generated avascular zones are critical regulators of mammalian cardiovascular patterning and are the first to identify a repulsive role for the lateral plate mesoderm. Integration of multiple, and in some cases redundant, repulsive cues from various tissues is critical to patterning the first embryonic blood vessels.
Liposomal Irinotecan
Authors: Corrie Lynn Messerer, Euan C. Ramsay, Dawn Waterhouse, Rebecca Ng, Eva-Maria Simms, Natashia Harasym, Paul Tardi, Lawrence D. Mayer, Marcel B. Bally
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose is to demonstrate whether an appropriately designed liposomal formulation of irinotecan is effective in treating mice with liver-localized colorectal carcinomas. Experimental Design: Irinotecan was encapsulated in 1,2-distearoyl-sn-glycero-3-phosphocholine/cholesterol (55:45 molar ratio) liposomes using an ionophore (A23187)-generated transmembrane proton gradient. This formulation was evaluated in vivo by measuring plasma elimination of liposomal lipid and drug after i.v. administration. Therapeutic activity was determined in SCID/Rag-2M mice bearing s.c. LS180 tumors or orthotopic LS174T colorectal metastases. Results: Drug elimination from the plasma was significantly reduced when irinotecan was administered in the liposomal formulation. At 1 hour after i.v. administration, circulating levels of the liposomal drug were 100-fold greater than that of irinotecan given at the same dose. High-performance liquid chromatographic analysis of plasma samples indicated that liposomal irinotecan was protected from inactivating hydrolysis to the carboxylate form. This formulation exhibited substantially improved therapeutic effects. For the LS180 solid tumor model, it was shown that after a single injection of liposomal irinotecan at 50 mg/kg, the time to progress to a 400-mg tumor was 34 days (as compared with 22 days for animals treated with free drug at an equivalent dose). In the model of colorectal liver metastases (LS174T), a median survival time of 79 days was observed after treatment with liposomal irinotecan (50 mg/kg, given every 4 days for a total of three doses). Saline and free drug treated mice survived for 34 and 53 days, respectively. Conclusions: These results illustrate that liposomal encapsulation can substantially enhance the therapeutic activity of irinotecan and emphasize the potential for using liposomal irinotecan to treat liver metastases.
AN UNUSUAL CASE OF LEPROSY.
Authors: N. MUKERJEE, S. GHOSH, S. KUNDU
Journal: British Journal of Dermatology (1958)

Journal Article AN UNUSUAL CASE OF LEPROSY. Get access N. MUKERJEE, M.B., B.S., D.T.M., D.P.H.(Cal.), N. MUKERJEE, M.B., B.S., D.T.M., D.P.H.(Cal.) Officer‐in‐Charge Leprosy Research Department, School of Tropical Medicine, Calcutta Search for other works by this author on: Oxford Academic Google Scholar S. GHOSH, M.B., B.S.(Cal), D.T.M.(Cal.) D. Bact.(Lond.), S. GHOSH, M.B., B.S.(Cal), D.T.M.(Cal.) D. Bact.(Lond.) Asst. Professor Leprosy Research Department, School of Tropical Medicine, Calcutta Search for other works by this author on: Oxford Academic Google Scholar S. KUNDU, M.B., B.S., D.T.M. & H.(Cal.) S. KUNDU, M.B., B.S., D.T.M. & H.(Cal.) Asst. Professor Leprosy Research Department, School of Tropical Medicine, Calcutta Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 70, Issue 8-9, 1 August 1958, Pages 300–301, https://doi.org/10.1111/j.1365-2133.1958.tb13344.x Published: 01 August 1958
Human epidermal growth factor receptor 2 overexpression in breast cancer of patients with anti-Yo-associated paraneoplastic cerebellar degeneration
Authors: I. Rojas-Marcos, G. Picard, D. Chinchon, E. Gelpi, D. Psimaras, B. Giometto, J. Y. Delattre, J. Honnorat, F. Graus
Journal: Neuro-Oncology (2012)

Isolated case reports suggest that breast tumors from patients with paraneoplastic cerebellar degeneration (PCD) and Yo antibodies overexpress human epidermal growth factor receptor 2 (HER2). HER2 overexpression is present in 15%-25% of breast cancers and is associated with poor prognosis. We retrospectively analyzed the status of HER2 in breast tumors of 27 patients with anti-Yo-associated PCD to evaluate whether HER2 overexpression in this group of patients is higher than expected. In addition, we analyzed HER2 status of 19 breast tumors from patients with paraneoplastic neurological syndromes and Ri antibodies to see whether HER2 was specifically related to anti-Yo-associated PCD. We also assessed cdr2 expression (the onconeural antigen recognized by Yo antibodies) in 21 HER2-positive breast tumors from patients without paraneoplastic neurological syndromes. HER2 was overexpressed in 26 patients (96.3%) with anti-Yo-associated PCD but only in 2 patients (10.5%) with paraneoplastic neurological syndromes associated with Ri antibodies (P< .0001). Only 5 (23.8%) of the 21 HER2-positive breast tumors showed cdr2 immunoreactivity. This study shows a very high frequency of HER2 overexpression in breast cancers in patients with anti-Yo-associated PCD but not in those from patients with Ri antibodies. Although the expression of cdr2 onconeural antigen is not high in HER2-positive breast cancers, HER2 overexpression seems to be an important requirement to develop an anti-Yo-associated PCD.
Are International Asthma Guidelines effective for low-income Brazilian children with asthma?
Authors: AL Cabral, WA Carvalho, M Chinen, RM Barbiroto, FM Boueri, MA Martins
Journal: European Respiratory Journal (1998)

The present study was designed to evaluate the effectiveness of International Asthma Guidelines in low-income asthmatic children in the city of Sao Paulo, Brazil. Fifty children with moderate or severe asthma were evaluated. Patients were evaluated before and after a 1 yr follow-up period using a pre- and post-education design with patients acting as their own controls. Parents were interviewed before and 1 yr after the programme. Most of the children were receiving inadequate medical care from their primary physicians, based mainly on bronchodilators. After the educational programme combined with a medical treatment based mainly on inhaled steroids, there was a decrease in emergency room visits and no need for hospital admissions. There was also a significant decrease in asthma severity and impairment scores (p&lt;.0001). The combination of good medical care and an educational programme can reduce the symptoms of asthma and significantly increase the quality of life, as well as decreasing the costs of asthma treatment. We conclude that by applying the International Asthma Guidelines substantial success was achieved, resulting in moving the patients from crises-orientated management into a chronic care and preventive management mode.
The IOC Diploma programme in sports physiotherapy
Authors: Benjamin Clarsen, Håvard Moksnes, Ronald J Maughan, Lars Engebretsen, Richard Budgett
Journal: British Journal of Sports Medicine (2015)

In recognition of the important role physiotherapists play in the medical care of athletes, the Medical Commission of the IOC is about to launch a postgraduate-level training programme in sports physiotherapy. At the 2014 IOC World Conference in prevention of Injuries and Illness in Sport, Lars Engebretsen (IOC Head of Scientific Activities) highlighted that this initiative is a part of the IOC's ongoing commitment to the protection of athletes’ health, and it builds on IOC's existing training programmes including the IOC Diplomas in Sports Nutrition and Sports Medicine.1

The programme is designed to meet the needs of physiotherapists caring for elite athletes, in particular those …
Branch-duct intraductal papillary mucinous neoplasms of the pancreas: to operate or not to operate?
Authors: R. Salvia, S. Crippa, M. Falconi, C. Bassi, A. Guarise, A. Scarpa, P. Pederzoli
Journal: Gut (2006)

Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas are reported to be less aggressive than the main-duct type. Hence, less aggressive treatment has been proposed for the former.To evaluate the effectiveness of a follow-up protocol for BD-IPMNs.Prospective study.An academic tertiary referral centre.From 2000 to 2003, 109 patients with BD-IPMNs underwent trans-abdominal ultrasound and magnetic resonance cholangiopancreatography with secretin. Patients who presented malignancy-related parameters (size >3.5 cm, nodules, thick walls, carbohydrate antigen 19.9 level >25 U/l, recent-onset or worsened diabetes) and/or complained of symptoms were submitted to surgery (arm A). All asymptomatic patients without suspicion of malignancy were followed up according to a 6-month clinical-radiological protocol (arm B).The effectiveness of conservative management of BD-IPMNs.20 (18.3%) patients underwent surgery (arm A); pathological diagnosis of BD-IPMNs was always confirmed. 89 (81.7%) patients were followed up for a median of 32 months (arm B); of these, 57 (64%) patients had multifocal disease. After a mean follow-up of 18.2 months, 5 (5.6%) patients showed an increase in lesion size and underwent surgery. The pathological diagnosis was branch-duct adenoma in three patients and borderline adenoma in two.Surgery is indicated in <20% of cases of BD-IPMNs, and, in the absence of malignancy-related parameters, careful non-operative management seems to be safe and effective in asymptomatic patients. Although observation for a longer time is needed to confirm these results, our findings support the guidelines recently recommended by the International Association of Pancreatology.
Successful use of rituximab in a patient with recalcitrant livedoid vasculopathy
Authors: P Zeni, E Finger, M A Scheinberg
Journal: Annals of the Rheumatic Diseases (2008)

Livedoid vasculopathy (LV) is a chronic recurrent painful cutaneous disease characterised by foci of purpuric lesions that convert to shallow ulcerations that progress to atrophic scar-like plaques mixed with telangiectasia and hyperpigmentation.1 2 Although of unknown aetiology, LV strongly correlates with immune complex associated diseases that lead to dermal vessel occlusion,3 and its histology consistently exhibits inflammatory infiltrates.4 Laboratory abnormalities consist essentially of a hypercoagulable state.5 Treatment of LV is usually empirical and based on immunosuppression with high-dose steroids, azathioprine, methotrexate and anticoagulation.6 In this report, we present a patient …