tbuckley/cabot-search huggingface dataset:
Effects of Low-Dose and Early versus Late Perindopril Treatment on the Progression of Severe Diabetic Nephropathy in (mREN-2)27 Rats
Authors: Sally A. Mifsud, Sandford L. Skinner, Mark E. Cooper, Darren J. Kelly, Jennifer L. Wilkinson-Berka
Journal: Journal of the American Society of Nephrology (2002)

It was previously reported that transgenic (mRen-2)27 rats with streptozotocin-induced diabetes mellitus progressively develop advanced nephropathy in 12 wk. These lesions are largely prevented when the angiotensin-converting enzyme inhibitor perindopril is administered from the time of induction of diabetes mellitus. This study aimed to determine the lowest dose of early perindopril treatment required for substantial improvement of renal function and structure and to investigate whether late intervention prevents or reverses the progression of established renal lesions. At 6 wk of age, female heterozygous Ren-2 rats were randomized to receive either streptozotocin (diabetic) or citrate buffer (control). Rats were gavaged, beginning early after the induction of diabetes mellitus or the administration of control vehicle, with 0, 0.02, 0.2, or 2 mg/kg per d perindopril for 12 wk. A separate group of diabetic Ren-2 rats received late treatment with 2 mg/kg per d perindopril throughout week 8 to week 12, when rats were hypertensive and albuminuric and exhibited increased kidney weight and glomerulosclerotic index (GSI). Among diabetic rats, early 0.02 mg/kg per d perindopril treatment reduced systolic BP, GSI, and renal collagen staining but had no effect on albuminuria or kidney hypertrophy. Early 0.2 or 2 mg/kg per d perindopril treatment further reduced systolic BP, GSI, and renal collagen staining and decreased albuminuria and kidney hypertrophy. Late intervention was as antihypertensive and antialbuminuric as early 0.2 or 2 mg/kg per d perindopril treatment but did not prevent a moderate increase in GSI. In conclusion, early treatment with 0.2 mg/kg per d perindopril was the lowest dosage to largely prevent severe diabetic nephropathy in transgenic Ren-2 rats. Late-onset perindopril treatment of diabetic rats with established nephropathy was as efficacious as early treatment with respect to various renal parameters, such as albuminuria, but was associated with moderate progression of glomerulosclerosis.
Kidney Transplantation: Mechanisms of Rejection and Acceptance
Authors: Lynn D. Cornell, R. Neal Smith, Robert B. Colvin
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

We describe the molecular and cellular mechanisms believed to be responsible for the rejection of renal allografts, including acute T cell-mediated rejection, acute antibody-mediated (humoral) rejection, rejection mediated by the innate immune system, and chronic rejection. We present mechanisms of graft acceptance, including accommodation, regulation, and tolerance. Studies in animals have replicated many pathologic features of acute and chronic rejection. We illuminate the pathogenesis of human pathology by reflection from experimental models.
Effects of Steroid Treatment On Outcomes in Patients with Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome
Authors: Elina Jerschow, Mili Shum, Denisa Ferastraoaru, Sharon Yee, Sunit Jariwala, Anna Tavdy, Golda Hudes, David L. Rosenstreich
Journal: Journal of Allergy and Clinical Immunology (2013)
Compulsive Hoarding: OCD Symptom, Distinct Clinical Syndrome, or Both?
Authors: Alberto Pertusa, Miguel A. Fullana, Satwant Singh, Pino Alonso, José M. Menchón, David Mataix-Cols
Journal: American Journal of Psychiatry (2008)

Compulsive hoarding is a debilitating problem that is often associated with obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder. However, the precise nosology of compulsive hoarding has yet to be determined.Participants were 25 patients with severe compulsive hoarding with OCD and 27 patients with severe compulsive hoarding without OCD. Both groups were carefully characterized and compared on the following sociodemographic and clinical variables: precise phenomenology of hoarding behavior, severity of other OCD symptoms, axis I and axis II psychopathology, and adaptive functioning. For comparison purposes, the following individuals were also recruited: 71 patients with OCD without hoarding, 19 patients with anxiety disorder, and 21 community participants.Overall, the phenomenology of hoarding behavior was similar in the two hoarding groups. The majority of participants in both groups reported hoarding common items as a result of their emotional and/or intrinsic value. However, approximately one-fourth of participants in the compulsive hoarding with OCD group showed a different psychopathological profile, which was characterized by the hoarding of bizarre items and the presence of other obsessions and compulsions related to their hoarding, such as fear of catastrophic consequences, the need to perform checking rituals, and the need to perform mental compulsions before discarding any item. These patients had a more severe and disabling form of the disorder. The strong relationship between compulsive hoarding and obsessive-compulsive personality disorder was explained entirely by the overlapping item content.In most individuals, compulsive hoarding appears to be a syndrome separate from OCD, which is associated with substantial levels of disability and social isolation. However, in other individuals, compulsive hoarding may be considered a symptom of OCD and has unique clinical features. These findings have implications for the classification of OCD and compulsive hoarding in the next edition of DSM.
Remodeling of Cell-Cell and Cell–Extracellular Matrix Interactions at the Border Zone of Rat Myocardial Infarcts
Authors: Tsutomu Matsushita, Masahito Oyamada, Kazushi Fujimoto, Yuko Yasuda, Shinsuke Masuda, Yukio Wada, Takahiro Oka, Tetsuro Takamatsu
Journal: Circulation Research (1999)

Abstract —At the border zone of myocardial infarcts, surviving cardiomyocytes achieve drastic remodeling of cell-cell and cell–extracellular matrix interactions. Spatiotemporal changes in these interactions are likely related to each other and possibly have significant impact on cardiac function. To elucidate the changes, we conducted experimental infarction in rats and performed 3-dimensional analysis of the localization of gap junctions (connexin43), desmosomes (desmoplakin), adherens junctions (cadherin), and integrins (β 1 -integrin) by immunoconfocal microscopy. After myocardial infarction, changes in the distribution of gap junctions, desmosomes, and adherens junctions showed a similar but nonidentical tendency. In the early phase, gap junctions almost disappeared at stumps (longitudinal edges of cardiomyocytes facing the infarct), and, although desmosomes and adherens junctions decreased, they still remained. In the healing phase, at stumps, connexin43, desmoplakin, and cadherin were closely associated between multiple cell processes originating from a single cardiomyocyte. Electron microscopy confirmed the presence of junctional complexes between the cell processes. β 1 -Integrin at the cell process increased during the formation of papillary myotendinous junction–like structures. Abnormal localization of connexin43 was often accompanied by desmoplakin and cadherin on lateral surfaces of surviving cardiomyocytes. These findings suggested that remodeling of gap junction distribution was closely linked to changes in desmosomes and adherens junctions and that temporary formation of intracellular junctional complexes was an element of the remodeling of cell-cell and cell–extracellular matrix interactions after myocardial infarction. Moreover, the remodeling of the intercalated disk region at the myocardial interface with area of scar tissues was associated with the acquisition of extracellular matrix and β 1 -integrin.
A TrkB–STAT3–miR-204-5p regulatory circuitry controls proliferation and invasion of endometrial carcinoma cells
Authors: Wei Bao, Hui-Hui Wang, Fu-Ju Tian, Xiao-Ying He, Mei-Ting Qiu, Jing-Yun Wang, Hui-Juan Zhang, Li-Hua Wang, Xiao-Ping Wan
Journal: Molecular Cancer (2013)

We previously identified TrkB as an oncogene involved in promoting metastasis in endometrial carcinoma (EC). Here, we sought to delineate the effect of changes in TrkB expression on the global profile of microRNAs (miRNAs) in EC cells and further investigated the correlation between the expression of certain miRNA and TrkB in the clinicopathologic characteristics of EC patients. Using quantitative reverse transcription-PCR (qRT-PCR), we found that expression of TrkB mRNA has no significant difference in transcript levels between normal endometrium and EC cells captured by laser capture microdissection, while immunohistochemistry results demonstrated a markedly higher expression of TrkB protein in EC tissues. The microRNA array showed that ectopic overexpression and knockdown of TrkB expression caused global changes in miRNA expression in EC cells. qRT-PCR results showed that elevated TrkB repressed miR-204-5p expression in EC cells. Furthermore, immunoblotting assays revealed that TrkB overexpression in IshikawaTrkB cells noticeably increased JAK2 and STAT3 phosphorylation, which, however, was aborted by TrkB knockdown in HEC-1BshTrkB cells. Moreover, ChIP assays showed that phospho-STAT3 could directly bind to STAT3-binding sites near the TRPM3 promoter region upstream of miR-204-5p. Interestingly, using bioinformatics analysis and luciferase assays, we identified TrkB was a novel target of miR-204-5p. Functionally, the MTT assays, clonogenic and Transwell assays showed that miR-204-5p significantly suppressed the clonogenic growth, migration and invasion of EC cells. Furthermore, miR-204-5p also inhibited the growth of tumor xenografts bearing human EC cells. Importantly, we found lower miR-204-5p expression was associated with advanced FIGO stages, lymph node metastasis and probably a lower chance for survival in EC patients. This study uncovers a new regulatory loop involving TrkB/miR-204-5p that is critical to the tumorigenesis of EC and proposes that reestablishment of miR-204-5p expression could be explored as a potential new therapeutic target for this disease.
Homocysteine Increases Cyclin-Dependent Kinase in Aortic Rat Tissue
Authors: Barbara Lubec, Olga Labudova, Harald Hoeger, Adolf Muehl, Susanne Fang-Kircher, Manfred Marx, Wilhelm Mosgoeller, J. Gialamas
Journal: Circulation (1996)

Background Hyperhomocyst(e)inemia is strongly associated with occlusive arterial disease. A direct effect of homocysteine on the proliferation of smooth muscle cells was proposed recently. This observation led us to examine the effect of homocysteine on cyclin-dependent kinase, the starter of mitosis and reflecting proliferation. Methods and Results Seventy Him :OFA rats were divided into seven groups. For 12 weeks, 10 rats were fed homocysteine 25 mg/kg body weight per day, 10 were fed 50 mg/kg body wt per day, and 10 were fed 100 mg/kg body weight per day; 10 were given homocysteic acid 100 mg/kg body weight per day, 10 were administered cysteine 100 mg/kg body weight per day, and 10 were given ascorbic acid 270 mg/kg body weight per day. Ten remained untreated and served as controls. Aortic cyclin-dependent kinase was determined at the transcriptional (mRNA) and protein levels. Phosphokinase C and aortic homocyst(e)ine also were evaluated in aortic tissue. Aortic cyclin-dependent kinase protein was significantly ( P =.0001) elevated in the three homocysteine-treated groups, and mRNA cyclin-dependent kinase levels were significantly elevated in the rats given the 50 and 100 mg/kg body weight per day protocol. Endothelial damage was shown at higher homocysteine doses as reflected by circulating ACE and von Willebrand factor changes. Proliferation of cells of the aortic wall by bromodeoxyuridine incorporation could be shown in the high-dose homocysteine group only. Conclusions Our findings indicate that homocysteine specifically stimulates aortic cyclin-dependent kinase at the transcriptional level, with the possible consequence of proliferation of aortic cells as revealed by incorporation of bromodeoxyuridine in the aortic wall.
Safety of triflusal (antiplatelet drug) in patients with aspirin‐exacerbated respiratory diseases
Authors: J. Fraj, A. Valero, R. Vives, I. Pérez, J. Borja, I. Izquierdo, C. Picado
Journal: Allergy (2007)

Aspirin, a cyclo-oxygenase (COX)-1 and COX-2 inhibitor, is the antiplatelet drug of choice to prevent serious vascular events. Adverse reactions to aspirin are frequent particularly among patients with asthma, chronic rhinosinusitis and nasal polyps. COX-1 inhibitors but not COX-2 inhibitors precipitate asthma attacks. Triflusal is a preferential COX-2 inhibitor antiplatelet agent that is as effective as aspirin in the prevention of serious vascular events. The aim of the study was to assess the tolerability of triflusal in patients with aspirin-exacerbated respiratory disease (AERD).We studied 26 asthma patients [11 males, aged 52 (23-75) years] who had suffered asthma episodes triggered by one or more (23% of patients) nonsteroidal anti-inflammatory drugs. Aspirin sensitivity was confirmed by either intranasal or oral aspirin challenge. All subjects underwent a single-blind, placebo-controlled oral challenge with three doses of triflusal separated by 1 week (first cumulative dose = 225 mg; second cumulative dose = 450 mg; third cumulative dose = 900 mg). Cutaneous, respiratory, general symptoms and lung function were monitored for 4 h in the laboratory and for 24 h at home.No clinical reactions to triflusal were observed. There were no significant changes in lung function measurements.Our study appears to demonstrate that triflusal is a suitable alternative to aspirin as antiplatelet agent to prevent AERD.
The intrahepatic signalling niche of hedgehog is defined by primary cilia positive cells during chronic liver injury
Authors: Candice Alexandra Grzelak, Luciano Gastón Martelotto, Nicholas David Sigglekow, Bramilla Patkunanathan, Katerina Ajami, Sarah Ruth Calabro, Benjamin James Dwyer, Janina Elke Eleonore Tirnitz-Parker, D. Neil Watkins, Fiona Jane Warner, Nicholas Adam Shackel, Geoffrey William McCaughan
Journal: Journal of Hepatology (2013)
The diagnostic utility of myositis autoantibody testing for predicting the risk of cancer-associated myositis
Authors: H. Chinoy, N. Fertig, C. V Oddis, W. E R Ollier, R. G Cooper
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> There is a known association between myositis and cancer. The risk is greater in dermatomyositis (DM) than polymyositis (PM), although reliable methods to predict cancer risk in specific patients with myositis are not presently available. This study was undertaken to determine whether risk of developing cancer in myositis can be predicted by antibody profiling. <h3>Methods:</h3> A cross-sectional study of UK Caucasian adults with PM (n = 109), DM (n = 103) and connective tissue disease overlap (myositis/CTD-overlap, n = 70). Patients were tested for a comprehensive range of myositis-specific/associated autoantibodies. Sensitivity and specificity analyses were performed for the optimal identification of cancer risk. <h3>Results:</h3> Sixteen patients had cancer-associated myositis (CAM) (15 DM, 1 myositis/CTD-overlap). CAM patients were older at disease onset, and patients without myositis-specific/associated autoantibodies on "routine" laboratory testing (negative for anti-Jo-1, anti-PM-Scl, anti-U1-RNP, anti-U3-RNP, anti-Ku antibodies) had a significantly increased risk of CAM. Possession of the antibody against 155 kDa and 140 kDa protein specificities (anti-155/140 antibody) represented a significant risk factor for CAM, and was found exclusively in DM. A positive anti-155/140 antibody result proved highly specific, moderately sensitive, with high negative predictive value for CAM. A "negative routine myositis antibody panel" result was highly sensitive, with high negative predictive value for CAM. The combination of these two approaches was 94% sensitive, detecting 15 of 16 CAM, with 100% sensitivity and negative predictive value in DM. <h3>Conclusions:</h3> These results may help clinicians predict which patients with myositis are at greater risk of developing cancer, thus identifying those requiring aggressive diagnostic evaluation and intensive cancer surveillance at myositis onset and follow-up.
Liposomal targeting of glucocorticoids to synovial lining cells strongly increases therapeutic benefit in collagen type II arthritis
Authors: J M Metselaar
Journal: Annals of the Rheumatic Diseases (2004)

To investigate the effect of a single intravenous treatment with glucocorticoids (GC) encapsulated in long-circulating PEG-liposomes on both joint inflammation and cartilage destruction and to investigate the phenomenon of selective homing of these liposomes in the inflamed synovium.Mice with collagen type II-induced arthritis (CIA) were intravenously treated with liposomal and free prednisolone phosphate (PLP) a few days after the first signs of the disease. Joint inflammation was scored during 1 week after treatment, after which sections of the knee joints were prepared for assessment of cartilage damage. In addition, arthritic mice were treated with liposomes containing colloidal gold. 24 hours after injection, knee joint sections were prepared in which the location of liposomes was visualised.Treatment of CIA with 10 mg/kg liposomal PLP resulted in a strong and lasting resolution of joint inflammation. 10 mg/kg free PLP only became slightly effective after repeated daily injections. Although joint inflammation recurred 1 week after treatment with liposomal PLP, knee joint sections prepared at this time indicated that the cartilage damage was still reduced. Localisation of gold labelled liposomes in the inflamed joints was seen in the proximity of blood vessels, in the cellular infiltrate, but mainly in the synovial lining. Unaffected joints did not take up liposomes.By using the property of long-circulating liposomes to target the synovial lining selectively in inflamed joints, the anti-inflammatory activity of GC can be greatly increased, showing also the beneficial effect of reduced cartilage destruction.
Athletic Injuries to the Knee
Authors: W. E. Tucker
Journal: BMJ (1937)

CHEMICAL DIAGNOSIS OF EARLY PREGNANCYMEDICEL IOUSAL 5252. Urines from sixty-five cases in which pregnancy diagnosis was required have been examined by the test.In all except one case the result was in agreement with that of the Friedman reaction.The advantages and dis- advantages of the test as compared with the biological tests are briefly discussed.In conclusion I have to express my warmest thanks to Messrs. Parke, Davis and Co. for a generous supply of pure crystalline oestriol (theelol), which has been used in this work as the standard control substance.My thanks are also due to Miss I. McPhee for her invaluable assistance in the carrying out of the manv extractions, and to Dr. A. R. Berrie and Mr.
Configuration and expression of the T cell receptor beta chain gene in human T-lymphotrophic virus I-infected cells.
Authors: R F Jarrett, H Mitsuya, D L Mann, J Cossman, S Broder, M S Reitz
Journal: The Journal of Experimental Medicine (1986)

We studied the configuration and expression of the gene encoding the beta chain of the T cell receptor (TCR beta) in cell lines and primary tumor cells infected by the human T cell leukemia/lymphoma (lymphotrophic) virus type I (HTLV-I). Most of the cell lines and all the primary tumor cells showed rearrangement of the TCR beta gene, and in each case the rearrangement was distinct. The majority of cases examined were clonal with respect to a particular TCR beta gene rearrangement. Primary tumor cells from one case (SD) were found to have a tandem duplication of a portion of chromosome 7; this appears to have resulted in the presence of three alleles of the TCR beta gene, each of which is arranged differently. This suggests that the chromosomal abnormality, and possibly infection by HTLV-I, occurred before TCR beta gene rearrangement. Cell lines infected by HTLV-I express levels of TCR beta mRNA similar to PHA stimulated lymphocytes, suggesting that this gene is not transcriptionally activated as a result of infection by HTLV-I. Cloned T cells of known antigen specificity that are infected by HTLV-I in vitro show impairment of immune function, including loss of antigen-specific responsiveness and the acquisition of alloreactivity. Comparison of the configuration of the TCR beta gene before and after infection revealed no changes detectable by Southern blot analysis. Levels of expression of the TCR beta gene at the mRNA level and surface expression of the T3 complex were also not significantly altered, suggesting that changes in immune function cannot be attributed to quantitative changes in the TCR molecule. The configuration of the TCR beta gene in primary tumor cells infected by HTLV-I was compared with that in the derived cell lines. In all pairs examined, the configuration in the primary tumor cells was different from that in the cell lines, strongly suggesting that the cells that grow in culture are not the original neoplastic cells.
The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus–induced microRNAs
Authors: Adelle P McFarland, Stacy M Horner, Abigail Jarret, Rochelle C Joslyn, Eckart Bindewald, Bruce A Shapiro, Don A Delker, Curt H Hagedorn, Mary Carrington, Michael Gale, Ram Savan
Journal: Nature Immunology (2013)
Analysis of Successful Immune Responses in Persons Infected with Hepatitis C Virus
Authors: Franziska Lechner, David K.H. Wong, P. Rod Dunbar, Roger Chapman, Raymond T. Chung, Paul Dohrenwend, Gregory Robbins, Rodney Phillips, Paul Klenerman, Bruce D. Walker
Journal: The Journal of Experimental Medicine (2000)

Although hepatitis C virus (HCV) infection is very common, identification of patients during acute infection is rare. Consequently, little is known about the immune response during this critical stage of the disease. We analyzed the T lymphocyte response during and after acute resolving HCV infection in three persons, using interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and human histocompatibility leukocyte antigen (HLA) peptide tetramer assays. Acute infection was associated with a broadly directed T helper and cytotoxic T lymphocyte (CTL) response, which persisted after resolution of clinical hepatitis and clearance of viremia. At the earliest time point studied, highly activated CTL populations were observed that temporarily failed to secrete IFN-γ, a “stunned” phenotype, from which they recovered as viremia declined. In long-term HCV-seropositive persons, CTL responses were more common in persons who had cleared viremia compared with those with persistent viremia, although the frequencies of HCV-specific CTLs were lower than those found in persons during and after resolution of acute HCV infection. These studies demonstrate a strong and persistent CTL response in resolving acute HCV infection, and provide rationale to explore immune augmentation as a therapeutic intervention in chronic HCV infection.