tbuckley/cabot-search huggingface dataset:
Beta 2-microglobulin amyloidosis in chronic dialysis patients
Authors: J Farrell, B Bastani
Journal: Journal of the American Society of Nephrology (1997)

Dialysis-related amyloidosis secondary to beta-2-microglobulin (beta 2m) deposits is a common complication of long-term dialysis patients and is responsible for significant morbidity with potential mortality. Beta 2m amyloid has a propensity to deposit in the osteoarticular tissues, particularly in large bones close to the joint spaces, and in synovial membranes and carpal tunnel tissue. Older age at the onset of dialysis and the duration of dialysis are two important risk factors for development of this disease. The high-flux, more biocompatible membranes have been shown to remove and adsorb beta 2m more efficiently than the cellulosic membranes. This study presents the case of a chronic dialysis patient who developed recurrent arthritis of the left knee, followed by carpal tunnel syndrome; biopsy of the patient's knee showed very large aggregates of beta 2m amyloid deposits in the tendon sheets. A brief review of the literature on this subject is also presented.
Loss of Podocyte aPKCλ/ι Causes Polarity Defects and Nephrotic Syndrome
Authors: Tobias B. Huber, Bjo[Combining Diaeresis] Hartleben, Kirstin Winkelmann, Lisa Schneider, Jan U. Becker, Michael Leitges, Gerd Walz, Hermann Haller, Mario Schiffer
Journal: Journal of the American Society of Nephrology (2009)

Atypical protein kinase C (aPKC) is a central component of the evolutionarily conserved Par3-Par6-aPKC complex, one of the fundamental regulators of cell polarity. We recently demonstrated that these proteins interact with Neph-nephrin molecules at the slit diaphragm of the glomerular filtration barrier. Here, we report that podocyte-specific deletion of aPKClambda/iota in mice results in severe proteinuria, nephrotic syndrome, and death at 4 to 5 wk after birth. Podocyte foot processes of knockout mice developed structural defects, including mislocalization of the slit diaphragm. In the glomerulus, aPKClambda/iota was primarily expressed in developing glomerular epithelial cells and podocyte foot processes. Interestingly, under physiologic conditions, aPKClambda/iota translocated from the apical surface to the basolateral side of developing podocytes, and this translocation preceded the development of foot processes and formation of slit diaphragms. Supporting a critical role for aPKClambda/iota in the maintenance of slit diaphragms and podocyte foot processes, aPKClambda/iota associated with the Neph-nephrin slit diaphragm complex and localized to the tips of filopodia and leading edges of cultured podocytes. These results suggest that aPKC signaling is fundamental to glomerular maintenance and development.
The differences in plantar loading between 3 positions related to the rugby scrum
Authors: Sally Brown, R Twycross-Lewis, N Padhiar
Journal: British Journal of Sports Medicine (2011)

Objective Foot injuries cause a significant absence from training and playing in the English rugby premiership. Pressure analysis gives information on how load is distributed, to give clinically relevant information this must be carried out in sports specific tasks. The aim of this study was to identify peak areas of pressure in the foot during three different positions related to the rugby scrum and their association to lower limb kinematics or stud formation. Methods Twenty-four male athletes were recruited from an English Premiership Rugby Club. An inner sole was inserted into the rugby boot to collect information on plantar pressure, the foot was divided into eight sections which were used to determine loading patterns. Three positions considered to be functionally relevant were studied, standing, engaged with a scrum machine and maximally pushing against the scrum machine. The Foot Posture Index, the weight bearing lunge test, first metatarsal extension and the number of studs were assessed. Results The medial forefoot showed the greatest load in the engaged and push positions (p&lt;0.05). Foot Posture Index was negatively correlated to forefoot pressures in standing (p&lt;0.05). Increase range of weight bearing lunge allowed for greater posterior lateral plantar loading during pushing (p&lt;0.05). Stud number was positively correlated to medial plantar pressure in standing and pushing (p&lt;0.05). Conclusion The substantial load on the medial forefoot in the rugby scrum suggests potential mechanisms for metatarsalphalangeal injury. Stud placement, foot posture index and range of weight bearing lunge can all influence plantar pressure. Future research should investigate mechanisms to reduce load in peak regions during the rugby scrum.
Short-Term Functional Adaptation of Aquaporin-1 Surface Expression in the Proximal Tubule, a Component of Glomerulotubular Balance
Authors: Marcus Pohl, Qixian Shan, Thomas Petsch, Beata Styp-Rekowska, Patricia Matthey, Markus Bleich, Sebastian Bachmann, Franziska Theilig
Journal: Journal of the American Society of Nephrology (2014)

Transepithelial water flow across the renal proximal tubule is mediated predominantly by aquaporin-1 (AQP1). Along this nephron segment, luminal delivery and transepithelial reabsorption are directly coupled, a phenomenon called glomerulotubular balance. We hypothesized that the surface expression of AQP1 is regulated by fluid shear stress, contributing to this effect. Consistent with this finding, we found that the abundance of AQP1 in brush border apical and basolateral membranes was augmented >2-fold by increasing luminal perfusion rates in isolated, microperfused proximal tubules for 15 minutes. Mouse kidneys with diminished endocytosis caused by a conditional deletion of megalin or the chloride channel ClC-5 had constitutively enhanced AQP1 abundance in the proximal tubule brush border membrane. In AQP1-transfected, cultured proximal tubule cells, fluid shear stress or the addition of cyclic nucleotides enhanced AQP1 surface expression and concomitantly diminished its ubiquitination. These effects were also associated with an elevated osmotic water permeability. In sum, we have shown that luminal surface expression of AQP1 in the proximal tubule brush border membrane is regulated in response to flow. Cellular trafficking, endocytosis, an intact endosomal compartment, and controlled protein stability are the likely prerequisites for AQP1 activation by enhanced tubular fluid shear stress, serving to maintain glomerulotubular balance.
Actin Cytoskeleton Organization and Posttranscriptional Regulation of Endothelial Nitric Oxide Synthase During Cell Growth
Authors: Charles D. Searles, Lucienne Ide, Michael E. Davis, Hua Cai, Martina Weber
Journal: Circulation Research (2004)

Posttranscriptional regulation of endothelial nitric oxide synthase (eNOS) expression is an important mechanism by which endothelial cells respond to various physiological and pathophysiological stimuli. Previously, we showed that eNOS expression was dramatically altered by the state of cell growth and that the mechanism responsible for this regulation was entirely posttranscriptional, occurring via changes in eNOS mRNA stability. The present study identifies a role for actin cytoskeleton organization in the posttranscriptional regulation of eNOS during cell growth and examines the relationship between the state of actin polymerization and eNOS expression. We identified monomeric actin (globular [G]-actin) as the major component of a 51-kDa ribonucleoprotein that binds to the eNOS mRNA 3' untranslated region in UV-crosslinking analysis. Binding activity of the ribonucleoprotein complex correlated with the relative concentration of G-actin versus filamentous actin (F-actin). ENOS transcripts colocalized with cytoplasmic G-actin in cells subjected to fluorescence in situ hybridization and G-actin fluorescence staining. In subcellular fractionation studies, eNOS transcripts were enriched in the free polysomal fraction of nonproliferating cells and enriched in the cell matrix-associated polysomal fraction of proliferating cells. Furthermore, an inverse relationship between the concentration of G-actin and eNOS expression was observed in endothelial cells subjected to pharmacological alteration of their cytoskeleton; lower G/F-actin ratios correlated with increased eNOS expression. Our findings provide some insight into how endothelial cells may use the dynamic organization of the actin cytoskeleton to regulate expression of an enzyme that is crucial to vascular homeostasis.
MELD and liver allocation: Continuous quality improvement
Authors: Richard B. Freeman
Journal: Hepatology (2004)

Isearch of the Medline Database done on August 1,2004, using "MELD and liver transplantation" A as the search terms, retrieved 84 citations with the first citation dating to 2001.This is evidence that over a 3-year period, the model for end-stage liver disease (MELD) score has been scrutinized more closely and rigorously than any other method for liver allocation and arguably more than any prognostic model in healthcare to date.This interest has been widespread throughout the world, with investigators from Europe, Asia, and South and North America all publishing reports examining various aspects of MELD, its use for and impact on liver allocation, and the results of liver transplantation.2Implementation of the MELD liver allocation system in the United States has been keenly followed, and there are efforts in several other areas of the world to utilize similar continuous disease severity scores for liver allocation.Why the interest?Why the acceptance?Why the scrutiny?In the United States, prior to implementation of the MELD-based liver allocation plan, candidates for liver transplantation were prioritized by location of care (outpatient, inpatient facility, or intensive care unit), and Child-Turcotte-Pugh score,3 which included subjective measures of encephalopathy and ascites, and time waiting on the list.As waiting lists grew, liver transplant practitioners became increasingly aware that these parameters were not good measures of disease severity and were subject to manipulation.Hence, there was dissatisfaction with the system in use at the time.At the same time, the US government required that the US liver allocation policy should use objective medical criteria to prioritize waiting candidates based on the severity of liver disease.*This necessitated development of a more objective measure of liver disease severity.The MELD score had been previously validated as a predictor of 3-month mortality for patients with chronic liver disease.These data, in combi-
Dramatic Increase in Autism Prevalence Parallels Explosion of Research Into Its Biology and Causes
Authors: Geraldine Dawson
Journal: JAMA Psychiatry (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Effects of High-Dose Folic Acid and Pyridoxine on Plasma and Erythrocyte Sulfur Amino Acids in Hemodialysis Patients
Authors: MOHAMED E. SULIMAN, JOSÉ C. DIVINO FILHO, PETER BÀRÀNY, BJÖRN ANDERSTAM, BENGT LINDHOLM, JONAS BERGSTROM
Journal: Journal of the American Society of Nephrology (1999)

Abstract. In this investigation, sulfur amino acids (sAA) and sulfhydryls were determined in the plasma and erythrocytes (RBC) of 10 uremic patients on regular hemodialysis (HD) treatment and 10 healthy subjects, before and after supplementation with 15 mg/d of folic acid and 200 mg/d of pyridoxine for 4 wk. The basal total plasma concentrations of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cys-Gly), γ-glutamylcysteine (γ-Glu-Cys), glutathione (GSH), and free cysteinesulfinic acid (CSA) were significantly higher in HD patients when compared to healthy subjects, whereas methionine (Met) and taurine (Tau) concentrations were the same in the two groups. HD patients showed significantly higher RBC levels of Hcy and Cys-Gly, whereas the RBC concentrations of Met, Cys, Tau, and GSH were not different from those in the healthy subjects. The plasma concentrations of sAA and sulfhydryls differed compared with RBC levels in the healthy subjects and HD patients. In both groups, supplementation with high doses of folic acid and pyridoxine reduced the plasma Hcy concentration. In addition, increased plasma concentrations of Cys-Gly and GSH were found in the HD patients and of CSA in the healthy subjects. After vitamin supplementation, the RBC concentrations of Hcy, Cys, and GSH increased and that of Tau decreased in healthy subjects. The only significant finding in RBC of HD patients was an increase in GSH levels after supplementation. This study shows several RBC and plasma sAA and sulfhydryl abnormalities in HD patients, which confirms earlier findings that RBC and plasma pools play independent roles in interorgan amino acid transport and metabolism. Moreover, high-dose supplementation with folic acid and pyridoxine significantly reduced Hcy levels, but did not restore the sAA and sulfhydryl abnormalities to normal levels. The increase that was observed in GSH after vitamin supplementation may have a beneficial effect in improving blood antioxidant status in uremic patients. Finally, the findings of elevated plasma Cys levels correlating to the elevated plasma Hcy levels in the presence of elevated plasma CSA levels, both before and after vitamin supplementation, led to the hypothesis that a block in decarboxylation of CSA is linked to hyperhomocysteinemia in end-stage renal failure.
Low-Density Lipoprotein Receptor Gene Mutations and Cardiovascular Risk in a Large Genetic Cascade Screening Population
Authors: Marina A.W. Umans-Eckenhausen, Eric J.G. Sijbrands, John J.P. Kastelein, Joep C. Defesche
Journal: Circulation (2002)

Background— A large cohort of patients with familial hypercholesterolemia (FH), free from selection for cardiovascular disease (CVD), and their unaffected relatives was collected by genetic cascade screening and examined for the influence of different mutations of the LDL receptor gene on lipoprotein levels and the risk of CVD. Multivariate analyses with adjustment for age, sex, and specific family ties were performed. Methods and Results— Significant variation of LDL levels was observed among 399 patients with FH with different mutations. Null alleles were associated with more severely elevated LDL cholesterol, whereas the frequent N543H/2393del9 mutation led to less elevated LDL cholesterol. The type of mutation did not influence HDL cholesterol levels. Patients with FH had CVD 8.5 times more often compared with their unaffected relatives (RR, 8.54; 95% CI, 5.29 to 13.80). The N543H/2393del9 mutation was associated with a smaller increase of risk compared with other mutations ( P &lt;0.0001). After exclusion of families with the N543H/2393del9 mutation, null alleles and other allele mutations no longer differed with regard to LDL cholesterol levels and CVD risk. Conclusions— LDL receptor mutations only partly contributed to the variation of LDL cholesterol levels and cardiovascular burden in FH. Additional, so far unidentified, familial risk factors must underlie the differences of CVD risk, most likely independent of lipids and lipoproteins.
Allergic Sensitization And Reported Adverse Reactions To Food In Ghanaian School Children: A Nested Case-control Study
Authors: B.B. Obeng, F.C. Hartgers, A.S. Amoah, I.A. Larbi, D.A. Boakye, R. van Ree, M. Yazdanbakhsh
Journal: Journal of Allergy and Clinical Immunology (2009)
Eph-B4 prevents venous adaptive remodeling in the adult arterial environment
Authors: Akihito Muto, Tai Yi, Kenneth D. Harrison, Alberto Dávalos, Tiffany T. Fancher, Kenneth R. Ziegler, Amanda Feigel, Yuka Kondo, Toshiya Nishibe, William C. Sessa, Alan Dardik
Journal: The Journal of Experimental Medicine (2011)

Eph-B4 determines mammalian venous differentiation in the embryo but is thought to be a quiescent marker of adult veins. We have previously shown that surgical transposition of a vein into the arterial environment is characterized by loss of venous identity, as indicated by the loss of Eph-B4, and intimal thickening. We used a mouse model of vein graft implantation to test the hypothesis that Eph-B4 is a critical determinant of venous wall thickness during postsurgical adaptation to the arterial environment. We show that stimulation of Eph-B4 signaling, either via ligand stimulation or expression of a constitutively active Eph-B4, inhibits venous wall thickening and preserves venous identity; conversely, reduction of Eph-B4 signaling is associated with increased venous wall thickness. Stimulated Eph-B4 associates with caveolin-1 (Cav-1); loss of Cav-1 or Eph-B4 kinase function abolishes inhibition of vein graft thickening. These results show that Eph-B4 is active in adult veins and regulates venous remodeling. Eph-B4–Cav-1–mediated vessel remodeling may be a venous-specific adaptive mechanism. Controlled stimulation of embryonic signaling pathways such as Eph-B4 may be a novel strategy to manipulate venous wall remodeling in adults.
Obese Individuals with Asthma Preferentially Have a High IL-5/IL-17A/IL-25 Sputum Inflammatory Pattern
Authors: Gudrun S. Marijsse, Sven F. Seys, An-Sofie Schelpe, Ellen Dilissen, Pieter Goeminne, Lieven J. Dupont, Jan L. Ceuppens, Dominique M. A. Bullens
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
The seborrhoeic pattern of dermatomyositis
Authors: I Katayama, Y Sawada, K Nishioka
Journal: British Journal of Dermatology (1999)

Sir, Heliotrope rash, Gottron's erythema and poikiloderma are well‐recognized cutaneous presentations in dermatomyositis.1 Cutaneous vasculitis, photosensitivity and Raynaud's phenomenon are often observed in adult patients with dermatomyositis, while cutaneous calcinosis is frequently observed in childhood dermatomyositis.2 In contrast to these well‐known cutaneous manifestations, facial fold erythema, seborrhoeic dermatitis‐like pattern, has rarely been reported in the literature, except for a recent report of scalp involvement in dermatomyositis in which five of 14 cases had been diagnosed as seborrhoeic dermatitis before the diagnosis of dermatomyositis was made.3 Aggravation of seborrhoeic dermatitis is occasionally seen in patients with acquired immunodeficiency syndrome (AIDS).4 Therefore, we studied retrospectively the presence of seborrhoeic dermatitis‐like manifestations in dermatomyositis. Eighteen patients with dermatomyositis were studied retrospectively with respect to skin manifestations, laboratory data and internal organ involvement (Table 1). They fulfilled the diagnostic criteria for dermatomyositis proposed by Bohan and Peter.5 The cutaneous manifestations seen in these patients were categorized into heliotrope rash, Gottron's sign, poikiloderma, ulcer and facial fold erythema. Facial fold erythema was defined as red, sharply marginated lesions localized to the facial folds, similar to seborrhoeic dermatitis.6 Facial fold erythema was found to be relatively frequent.
VIABLE LEISHMANIA DONOVANI IN NASAL AND ORAL SECRETIONS OF PATIENTS WITH KALA-AZAR AND THE BEARING OF THIS FINDING ON THE TRANSMISSION OF THE DISEASE
Authors: Claude E. Forkner, Lily S. Zia
Journal: The Journal of Experimental Medicine (1934)

1. Smears from the nasal cavities of fifteen patients suffering from kala-azar have been examined and in nine of these typical Leishman-Donovan bodies have been found. 2. Smears from the surface of the tonsil and from the saliva in one of the above nine cases showed the presence of leishmania. The tonsils of this patient, who died as the result of kala-azar and secondary infection, at autopsy were shown to be massively infected with Leishman-Donovan bodies. 3. Leishmania in the nasal discharge of two patients were shown by inoculation into susceptible animals to be viable and capable of producing infection. Sufficient time has not elapsed to determine the viability of the organisms from the remaining cases. 4. These experiments show for the first time that a rich source of infective material from a large proportion of patients with kala-azar is available for direct transmission of the disease. 5. Strong evidence is presented as a basis for the concept that one of the natural modes, perhaps the most important natural mode, of transmission of kala-azar is from person to person by way of the upper respiratory and alimentary tracts. 6. Two normal human volunteers and numerous normal experimental animals have been inoculated into the nasal and oral cavities with the nasal discharge, known to contain leishmania, from patients with kala-azar. The results of these experiments will be reported at a subsequent date.
Mta, the maternally transmitted antigen, is determined jointly by the chromosomal Hmt and the extrachromosomal Mtf genes.
Authors: K F Lindahl, B Hausmann, P J Robinson, J L Guénet, D C Wharton, H Winking
Journal: The Journal of Experimental Medicine (1986)

Mus spretus from four stocks, originating in Spain, Portugal, and Morocco, were tested for the maternally transmitted antigen, Mta. All expressed a variant form not found in other species of mice. Analysis of appropriate crosses with inbred mice showed that the spretus form of Mta is determined by a new allele, c, of the Hmt gene. The Hmtc allele has been isolated in coupling with four different H-2 haplotypes. It is possible to raise CTL specific for the spretus form of Mta. The maternally transmitted factor, Mtf alpha s, of spretus mice determines, in conjunction with the Hmta allele of C57BL/6, an Mta that is indistinguishable from the common form found in C57BL/6 and most other inbred mice. Our experiments show that the specificity of the cell surface antigen Mta is governed jointly by the cytoplasmic gene Mtf and the chromosomal gene Hmt. We propose that Hmt encodes a class I histocompatibility antigen that acts as a restricting element for the Mtf gene product, thus meeting the requirements of T killer cell recognition.