tbuckley/cabot-search huggingface dataset:
Efforts to Control the Errant Products of a Targeted <i>In vivo</i> Generator
Authors: Jaspreet Singh Jaggi, Barry J. Kappel, Michael R. McDevitt, George Sgouros, Carlos D. Flombaum, Catalina Cabassa, David A. Scheinberg
Journal: Cancer Research (2005)

Abstract Alpha-particle immunotherapy by targeted α-emitters or α-emitting isotope generators is a novel form of extraordinarily potent cancer therapy. A major impediment to the clinical use of targeted actinium-225 (225Ac) in vivo generators may be the radiotoxicity of the systemically released daughter radionuclides. The daughters, especially bismuth-213 (213Bi), tend to accumulate in the kidneys. We tested the efficacy of various pharmacologic agents and the effect of tumor burden in altering the pharmacokinetics of the 225Ac daughters to modify their renal uptake. Pharmacologic treatments in animals were started before i.v. administration of the HuM195-225Ac generator. 225Ac, francium-221 (221Fr), and 213Bi biodistributions were calculated in each animal at different time points after 225Ac generator injection. Oral metal chelation with 2,3-dimercapto-1-propanesulfonic acid (DMPS) or meso-2,3-dimercaptosuccinic acid (DMSA) caused a significant reduction (P &amp;lt; 0.0001) in the renal 213Bi uptake; however, DMPS was more effective than DMSA (P &amp;lt; 0.001). The results with DMPS were also confirmed in a monkey model. The renal 213Bi and 221Fr activities were significantly reduced by furosemide and chlorothiazide treatment (P &amp;lt; 0.0001). The effect on renal 213Bi activity was further enhanced by the combination of DMPS with either chlorothiazide or furosemide (P &amp;lt; 0.0001). Competitive antagonism by bismuth subnitrate moderately reduced the renal uptake of 213Bi. The presence of a higher target-tumor burden significantly prevented the renal 213Bi accumulation (P = 0.003), which was further reduced by DMPS treatment (P &amp;lt; 0.0001). Metal chelation, diuresis with furosemide or chlorothiazide, and competitive metal blockade may be used as adjuvant therapies to modify the renal accumulation of 225Ac daughters.
A novel TNFRSF1 gene mutation in a turkish family: report of three cases
Authors: F. Cosan, A. Yazici, A. Cefle, A. Gul
Journal: Annals of the Rheumatic Diseases (2010)

Background Tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autosomal dominantly inherited rare autoinfl ammatory disease.It caused by mutations in exon 2-3 and 4-5 of the TNFRSF1A gene on chromosome 12p13.2.TNFRSF1A gene encodes the 55 kDa receptor for TNF.Attacks are associated with abdominal pain, myalgia, erythematous skin rash, conjunctivitis and periorbital oedema.More than 80 mutations have so far been identifi ed.The authors report three patients of Turkish origin with TRAPS.Patients and Methods The patients were followed in our outpatient clinic in Kocaeli University Division of Rheumatology.Because of their TRAPS-associated clinical features, the authors isolated genomic DNA from whole blood and sequenced the exon 2-3 and 4-5 third exon of TNFRSF1A gene after amplification with appropriate primers.Results One of the patients with TRAPS, a 47-year-old woman, described recurrent attacks of fever, urticarial rash, conjunctivitis, athralgia, myalgia, abdominal pain, thoracic pain, headache, fatigue and elevated acute phase response since her childhood.With sequencing of the TNFRSF1A gene, the authors identifi ed heterozygous C29R mutation which has not been reported before in any TRAPS patient.The other patients were her sons (aged 29 and 26 years) with similar fi ndings in whom the authors also found a heterozygous C29R mutation. ConclusionThe authors report a novel C29R mutation in three patients of Turkish origin with TRAPS in whom the main clinical features were recurrent fever attacks, erythematous skin rash, conjunctivitis, myalgia and arthralgia.Treatment with steroids completely resolved the symptoms and lesions.on July 14,
Oral Administration of Glomerular Basement Membrane Prevents the Development of Experimental Autoimmune Glomerulonephritis in the WKY Rat
Authors: JOHN REYNOLDS, CHARLES D. PUSEY
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by a single injection of collagenase-solubilized rat glomerular basement membrane (GBM) in adjuvant. EAG is characterized by circulating and deposited anti-GBM antibodies, accompanied by focal necrotizing glomerulonephritis with crescent formation. The inhibitory effect of orally administered antigens has been reported in various animal models of autoimmunity but not in EAG in the rat. The effects of feeding rat GBM by gavage, at total doses of 0.5, 2.5, or 5 mg, before immunization were examined. A dose-dependent effect was observed on the development of EAG. A dose of 0.5 mg of GBM had no effect on disease, 2.5 mg resulted in a moderate reduction in the severity of nephritis but no change in anti-GBM antibody production, and 5 mg resulted in a marked reduction in circulating and deposited anti-GBM antibodies, albuminuria, deposits of fibrin in the glomeruli, severity of glomerular abnormalities, and numbers of infiltrating T cells and macrophages. Animals that were fed 5 mg of GBM showed a significant reduction in IgG2a but not IgG1, anti-GBM antibody levels, suggesting downregulation of Th1 responses. There was also a dose-dependent reduction in the proliferative responses of splenic T cells from treated animals to GBM antigen in vitro . These results clearly demonstrate that mucosal tolerance can be induced by oral administration of GBM antigen and that this approach is effective in preventing EAG.
N0539 phase II trial of fulvestrant and bevacizumab in patients with metastatic breast cancer previously treated with an aromatase inhibitor: a North Central Cancer Treatment Group (now Alliance) trial
Authors: W.W. Tan, A.C. Dueck, P. Flynn, P. Steen, D. Anderson, K. Rowland, D. Northfelt, E.A. Perez
Journal: Annals of Oncology (2013)
Note of a Case of Salivary Calculus Presenting Unusual Symptoms
Authors: A. M. Sheild
Journal: BMJ (1895)

THERE have lately been under my care three cases of malformation of the umbilicus which, owing to their compara- tive rarity and interest from a developmental point of view, have seemed to me to be worthy of record.CASE I. Large Congenital Exomphalos: Hernia of Intestines into a Thin Membranous Sac, Composed of the Dilated Umbdlical Cord: Abdominal Section: Recovery.-R.M. was admitted into the General Hospital on August 18th, 1892, four hours after birth, on account of a large membranous protrusion at the umbilicus.The infant, a female, was in other respects quite healthy and a full term child.Protruding from the umbilicus was a membranous sac about the size of a large orange, with thin transparent walls thickened on the right side, to which the umbilical cord was attached.Coils of intestine were plainly visible through the sac, which was evidently an expansion of the umbilical cord.The intestines eould not be reduced into the abdominal cavity.Chloroform was administered, the sac opened, and the neck of the umbilical aperture enlarged by a vertical incision above and below the umbilicus.Several coils of small intestine-one coil with a thin white cord attaching it to the fundus of the sac-were reduced into the abdomen.The eecum and vermiform ap- pendix were intimately adherent to the sac wall.As it was impossible to separate these latter, all the sac was cut away except where adherent to eecum, and this part was reduced into the abdomen along with the intestine.The abdomen was then closed with fine silk sutures.During that night and the whole of the following day the child vomited at frequent intervals.The vomit resembled coffee grounds.In the evening of August 19th the anus was well dilated with forceps.This gave vent to a quantity of meconium, and the child's recovery was afterwards uninterrupted.When seen a few months ago she was a strong healthy girl.This case is an example of a deformity occasionally met with in obstetric practice.The white cord attaching a coil of small intestine to the fundus of the sac was the fibrous remains of the vitello-intestinal duct.This and the adhesion of the caecum to the sac wall may perhaps account for the non-closure of the umbilicus.CASE II.Umbilical Faecal Fistula due to Persistence of the DDuctus Vitello-intestinalis Openiig at the Umbilicus: Death: lNecropsy.-J.Y., a puny male infant, was admitted into the Children's Hospital in October, 1894, with a large abnormal aperture at the umbilicus, through which all feees were dis-
Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis
Authors: Lin Chen, Rivka Adar, Xiao Yang, Efrat O. Monsonego, Cuiling Li, Peter V. Hauschka, Avner Yayon, Chu-Xia Deng
Journal: Journal of Clinical Investigation (1999)

Missense mutations in fibroblast growth factor receptor 3 (FGFR3) result in several human skeletal dysplasias, including the most common form of dwarfism, achondroplasia. Here we show that a glycine-to-cysteine substitution at position 375 (Gly375Cys) in human FGFR3 causes ligand-independent dimerization and phosphorylation of FGFR3 and that the equivalent substitution at position 369 (Gly369Cys) in mouse FGFR3 causes dwarfism with features mimicking human achondroplasia. Accordingly, homozygous mice were more severely affected than heterozygotes. The resulting mutant mice exhibited macrocephaly and shortened limbs due to retarded endochondral bone growth and premature closure of cranial base synchondroses. Compared with their wild-type littermates, mutant mice growth plates shared an expanded resting zone and narrowed proliferating and hypertrophic zones, which is correlated with the activation of Stat proteins and upregulation of cell-cycle inhibitors. Reduced bone density is accompanied by increased activity of osteoclasts and upregulation of genes that are related to osteoblast differentiation, including osteopontin, osteonectin, and osteocalcin. These data reveal an essential role for FGF/FGFR3 signals in both chondrogenesis and osteogenesis during endochondral ossification.
Elevated Plasma Asymmetric Dimethylarginine as a Marker of Cardiovascular Morbidity in Early Diabetic Nephropathy in Type 1 Diabetes
Authors: Lise Tarnow, Peter Hovind, Tom Teerlink, Coen D.A. Stehouwer, Hans-Henrik Parving
Journal: Diabetes Care (2004)

Increased plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, has been associated with endothelial dysfunction, insulin resistance, and atherosclerosis in nondiabetic populations. In end-stage renal failure, circulating ADMA is elevated and a strong predictor of cardiovascular outcome. This study investigated the relation between ADMA and diabetic micro- and macrovascular complications in a large cohort of type 1 diabetic patients with and without early diabetic nephropathy.ADMA concentrations in plasma were determined by a high-performance liquid chromatography method in 408 type 1 diabetic patients with overt diabetic nephropathy (252 men; mean age 42.7 years [SD 11.0], mean duration of diabetes 28 years [SD 9], median serum creatinine level 102 micromol/l [range 52-684]). A group of 192 patients with longstanding type 1 diabetes and persistent normoalbuminuria served as control subjects (118 men; mean age 42.6 years [SD 10.2], mean duration of diabetes 27 years [SD 9]).In patients with diabetic nephropathy, mean +/- SD plasma ADMA concentration was elevated 0.46 +/- 0.08 vs. 0.40 +/- 0.08 micromol/l in normoalbuminuric patients (P<0.001). An increase in plasma ADMA of 0.1 micromol/l increased the odds ratio of nephropathy to 2.77 (95% CI 1.89-4.05) (P<0.001). Circulating ADMA increased in nephropathy patients with declining kidney function, as indicated by elevated values in the lower quartiles of glomerular filtration rate (<76 ml.min(-1).1.73 m(-2)) (P<0.001 ANOVA). Mean ADMA levels were similar in patients with or without diabetic retinopathy (P>0.2). However, in 44 patients with nephropathy and history of myocardial infarction and/or stroke, ADMA was significantly elevated at 0.48 +/- 0.08 micromol/l compared with 0.46 +/- 0.08 micromol/l in patients without major cardiovascular events (P=0.05).Elevated circulating ADMA may contribute to the excess cardiovascular morbidity and mortality in early diabetic nephropathy.
Pharmacologic Treatment of Type 2 Diabetes
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2003)

This is the fifth in a series of articles covering the 2002 American Diabetes Association Annual Meeting, which was held in San Francisco, 14–18 June 2002.

At a symposium on pharmacologic therapy for diabetes prevention, Saul Genuth (Cleveland, OH), chairperson, commented that there is now evidence that three different classes of pharmacologic treatment, biguanides, α-glucosidase inhibitors, and thiazolidinediones (TZDs), are effective in preventing diabetes. Steven Kahn (Seattle, WA) discussed data from the Diabetes Prevention Program (DPP), showing evidence for efficacy of metformin in persons over age 25 years whose BMI exceeded 24 kg/m2 (22 in Asian Americans), with 2-h glucose between 140 and 199 and fasting plasma glucose (FPG) between 95 and 125 mg/dl. Those in the “intensive lifestyle” intervention group aimed to increase exercise by 150 min/week and to lose 7% of body weight, while those randomized to metformin received 850 mg twice daily; a third group received placebo. The average BMI was 34 kg/m2 and the average FPG was 105 mg/dl. The diagnosis of the primary outcome, diabetes, was based either on a 75-g oral glucose tolerance test (OGTT) with FPG or 2-h glucose exceeding 125 or 199 mg/dl, respectively, or on 6-month FPG exceeding 125. In the placebo group, diabetes developed at a rate of 11%/year, while with metformin, a 31% reduction was seen, and with lifestyle, a 58% reduction was seen. Metformin had an effect similar to lifestyle among those under age 45 years, but was less effective among older subjects. Persons with BMI exceeding 35 kg/m2 also showed efficacy of metformin similar to that of lifestyle, while neither sex nor ethnicity affected the efficacy of the agent. FPG increased slowly in the placebo group, while decreasing initially with subsequent increase to baseline at 3 years in the lifestyle and metformin groups. HbA …
Annexins and Ca handling in the heart
Authors: E CAMORS, V MONCEAU, D CHARLEMAGNE
Journal: Cardiovascular Research (2004)

Annexins are a family of 13 proteins known to bind phospholipids (PL) in a Ca(2+)-dependent way. They are ubiquitous proteins and share a similar structure characterized by a conserved C-terminal domain with Ca(2+) binding sites and a variable N-terminal domain. Depending on Ca(2+) concentration, they have been reported to participate in a variety of membrane-related events such as exocytosis, endocytosis, apoptosis and binding to cytoskeletal proteins. They have also been reported to regulate protein activities. This review will focus on annexins in the heart, and particularly on annexins A2, A5, A6 and A7. Annexin A2 has been found in endothelial cells and reported to play a central role in control of plasmin-mediated processes. Annexin A5 is mainly localized in cardiomyocytes. However, it could be relocated to interstitial tissue in ischemic and failing hearts or it could be externalized and exhibit a proapoptotic effect in cardiomyocytes. Annexin A6 is the most abundant annexin in the heart, and has been localized in various cell types including myocytes. Overexpression of annexin A6 has underlined physiological alterations in contractile mechanics leading to dilated cardiomyopathy, whereas knockout has been found to induce faster changes in Ca(2+) transient and increased contractility, suggesting a negative inotropic role for annexin A6. Annexin A7 is expressed in heart and skeletal muscle. In annexin A7 null mutant mice decreases in the force-frequency relationship were observed in adult cardiomyocytes, consistent with regulation of Ca(2+) handling. In conclusion, while annexin A2 was involved in regulation of fibrin homeostasis, alterations in expression and activity of annexins A5, A6 and A7 have been associated with regulation of Ca(2+) handling in the heart, but the target of each annexin has not yet been identified.
Contribution of Prolonged Ischemia and Donor Age to Chronic Renal Allograft Dysfunction
Authors: STEFAN GU[Combining Diaeresis]NTHER TULLIUS, ANJA REUTZEL-SELKE, FRANK EGERMANN, MELINA NIEMINEN-KELHA[Combining Diaeresis], SVEN JONAS, WOLF OTTO BECHSTEIN, HANS-DIETER VOLK, PETER NEUHAUS
Journal: Journal of the American Society of Nephrology (2000)

Abstract. As a consequence of an advancing discrepancy between supply of suitable grafts and demand from potential recipients, less than optimal organs are increasingly being used. Although clinical studies demonstrate the involvement of various risk factors, including donor age and duration of ischemia on long-term graft outcome, their individual contribution and correlation has not been followed experimentally. After cold ischemic times of 5, 60, and 120 min, kidney allografts of 3-, 12-, and 18-mo-old Fischer 344 donors were transplanted into 3-mo-old Lewis rats. Age-related changes were examined in matched native uninephrectomized controls. Proteinuria and creatinine clearance were determined, and histologic and immunohistologic studies were assessed and quantified at the end of the observation period (20 wk). All grafts functioned satisfactorily with the exception of one graft each from 12- and 18-mo-old donors with prolonged ischemia (120 min). Functional deterioration and structural changes progressed in parallel to increasing donor age and prolonged ischemia. The impact of expanded ischemia was particularly detrimental in grafts from older donor animals. Donor age and duration of ischemia act in a synergistic manner in our model. Brief ischemic times seem of particular relevance when grafts from older donors are being used.
Biomechanics of Trabecular Bone
Authors: Tony M. Keaveny, Elise F. Morgan, Glen L. Niebur, Oscar C. Yeh
Journal: Annual Review of Biomedical Engineering (2001)

▪ Abstract Trabecular bone is a complex material with substantial heterogeneity. Its elastic and strength properties vary widely across anatomic sites, and with aging and disease. Although these properties depend very much on density, the role of architecture and tissue material properties remain uncertain. It is interesting that the strains at which the bone fails are almost independent of density. Current work addresses the underlying structure-function relations for such behavior, as well as more complex mechanical behavior, such as multiaxial loading, time-dependent failure, and damage accumulation. A unique tool for studying such behavior is the microstructural class of finite element models, particularly the “high-resolution” models. It is expected that with continued progress in this field, substantial insight will be gained into such important problems as osteoporosis, bone fracture, bone remodeling, and design/analysis of bone-implant systems. This article reviews the state of the art in trabecular bone biomechanics, focusing on the mechanical aspects, and attempts to identify important areas of current and future research.
Yoga for Chronic Low Back Pain
Authors: Helen E. Tilbrook, Helen Cox, Catherine E. Hewitt, Arthur Ricky Kang'ombe, Ling-Hsiang Chuang, Shalmini Jayakody, John D. Aplin, Anna Semlyen, Alison Trewhela, Ian Watt, David J. Torgerson
Journal: Annals of Internal Medicine (2011)

Background: Previous studies indicate that yoga may be an effective treatment for chronic or recurrent low back pain. Objective: To compare the effectiveness of yoga and usual care for chronic or recurrent low back pain. Design: Parallel-group, randomized, controlled trial using computer-generated randomization conducted from April 2007 to March 2010. Outcomes were assessed by postal questionnaire. (International Standard Randomised Controlled Trial Number Register: ISRCTN 81079604) Setting: 13 non–National Health Service premises in the United Kingdom. Patients: 313 adults with chronic or recurrent low back pain. Intervention: Yoga (n = 156) or usual care (n = 157). All participants received a back pain education booklet. The intervention group was offered a 12-class, gradually progressing yoga program delivered by 12 teachers over 3 months. Measurements: Scores on the Roland–Morris Disability Questionnaire (RMDQ) at 3 (primary outcome), 6, and 12 (secondary outcomes) months; pain, pain self-efficacy, and general health measures at 3, 6, and 12 months (secondary outcomes). Results: 93 (60%) patients offered yoga attended at least 3 of the first 6 sessions and at least 3 other sessions. The yoga group had better back function at 3, 6, and 12 months than the usual care group. The adjusted mean RMDQ score was 2.17 points (95% CI, 1.03 to 3.31 points) lower in the yoga group at 3 months, 1.48 points (CI, 0.33 to 2.62 points) lower at 6 months, and 1.57 points (CI, 0.42 to 2.71 points) lower at 12 months. The yoga and usual care groups had similar back pain and general health scores at 3, 6, and 12 months, and the yoga group had higher pain self-efficacy scores at 3 and 6 months but not at 12 months. Two of the 157 usual care participants and 12 of the 156 yoga participants reported adverse events, mostly increased pain. Limitation: There were missing data for the primary outcome (yoga group, n = 21; usual care group, n = 18) and differential missing data (more in the yoga group) for secondary outcomes. Conclusion: Offering a 12-week yoga program to adults with chronic or recurrent low back pain led to greater improvements in back function than did usual care. Primary Funding Source: Arthritis Research UK.
The fight against doping is a fight for the protection of the clean athlete, the health of the athlete and the integrity of sport
Authors: Arne Ljungqvist
Journal: British Journal of Sports Medicine (2014)

The consensus document published in this issue of BJSM contributes significantly to the ongoing fight against doping which started some 50 years ago. Following its creation in the 1960s, the IOC Medical Commission developed antidoping rules to be applied at the Olympic Games; these rules were amended before each game. One international federation after the other adopted the IOC rules and modified them specifically for their sport. Also some national sports bodies adopted particular antidoping rules which were, however, country specific.

### The birth of the World Anti-Doping Agency

When antidoping activities accelerated following the Ben Johnson case at the Seoul games in 1988 …
PPARγ Activation: A Potential Treatment For Pulmonary Hypertension
Authors: Georg Hansmann, Roham T. Zamanian
Journal: Science Translational Medicine (2009)

Pharmacological activation of the transcription factor PPARγ affects the expression of key genes involved in the development of pulmonary hypertension (PH), subsequently has a variety of beneficial effects in the vasculature, and hence might be a powerful treatment of PH.
Mechanisms for the induction of autoimmunity by infectious agents
Authors: Kai W. Wucherpfennig
Journal: Journal of Clinical Investigation (2001)

Autoimmune diseasesActivation and clonal expansion of autoreactive lymphocytes is a critical step in the pathogenesis of autoimmune diseases.In experimental models of autoimmunity, disease can be transferred by activated, but not resting, autoreactive T cells (1), indicating that activation of autoreactive T cells is required for the development of autoimmune diseases.Infectious agents have long been considered as possible culprits in the activation of autoreactive T cells.Mechanisms by which an infection can lead to an autoimmune process have been examined in experimental animal models, and these concepts as well as their relevance to human diseases will be discussed here.