tbuckley/cabot-search huggingface dataset:
Monocyte-specific Bcl-2 expression attenuates inflammation and heart failure in monocyte chemoattractant protein-1 (MCP-1)-induced cardiomyopathy☆
Authors: J NIU, A AZFER, P KOLATTUKUDY
Journal: Cardiovascular Research (2006)

Infiltrating inflammatory cells within the myocardium have been shown to be apoptotic, but the significance of apoptotic inflammatory cells to the development of cardiomyopathy remains undefined. Transgenic mice with cardiac-specific expression of MCP-1 exhibit extensive apoptosis of infiltrating mononuclear cells and develop heart failure. Here, we tested the hypothesis that in vivo selective inhibition of apoptosis of infiltrating mononuclear cells would preserve cardiac structure and function and improve survival in this murine model.Mice with cardiac-specific expression of MCP-1 and monocyte-specific expression of Bcl-2 were generated by cross-breeding MCP-1 transgenic mice with hMRP8-Bcl-2 mice that over-express Bcl-2 in the monocytes. Structural and functional parameters and the inflammatory response of the heart were evaluated and compared between the wild-type and transgenic mice.Expression of Bcl-2 in monocytes results in superior preservation of myocardial structure, cardiac function and a significant prolongation of survival of MCP-1 transgenic mice. The beneficial effects of monocyte-specific Bcl-2 expression are associated with inhibition of apoptosis of infiltrating mononuclear cells, normalization of circulating C-reactive protein levels, attenuation of cellular infiltrates, macrophage activation and production of proinflammatory cytokines, tumor necrosis factor (TNF-alpha), interleukin (IL)-1 beta and IL-6 in the hearts.These results demonstrate that apoptosis of infiltrating mononuclear cells plays a detrimental role in the development of heart failure in this murine model, suggesting that modulation of apoptosis of infiltrating mononuclear cells may be of clinical benefit in heart failure.
Placental Transfusion at Birth
Authors: Michael Posencheg, Haresh Kirpalani
Journal: JAMA Pediatrics (2014)

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 Pediatrics 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 Pediatrics journal
ADVANCED PROTEIN GLYCOSYLATION IN DIABETES AND AGING
Authors: Michael Brownlee, M.D
Journal: Annual Review of Medicine (1995)

▪ Abstract Products of advanced protein glycosylation (advanced glycation end products, or AGEs) accumulate in tissues as a function of time and sugar concentration. AGEs induce permanent abnormalities in extracellular matrix component function, stimulate cytokine and reactive oxygen species production through AGE-specific receptors, and modify intracellular proteins. Pharmacologic inhibition of AGE formation in long-term diabetic animals prevents diabetic retinopathy, nephropathy, neuropathy, and arterial abnormalities in animal models. Clinical trials in humans are currently in progress.
Epigenomic Profiling Reveals Novel and Frequent Targets of Aberrant DNA Methylation-Mediated Silencing in Malignant Glioma
Authors: Tae-You Kim, Sheng Zhong, C. Robert Fields, Jeong Hoon Kim, Keith D. Robertson
Journal: Cancer Research (2006)

Abstract Malignant glioma is the most common central nervous system tumor of adults and is associated with a significant degree of morbidity and mortality. Gliomas are highly invasive and respond poorly to conventional treatments. Gliomas, like other tumor types, arise from a complex and poorly understood sequence of genetic and epigenetic alterations. Epigenetic alterations leading to gene silencing, in the form of aberrant CpG island promoter hypermethylation and histone deacetylation, have not been thoroughly investigated in brain tumors, and elucidating such changes is likely to enhance our understanding of their etiology and provide new treatment options. We used a combined approach of pharmacologic inhibition of DNA methylation and histone deacetylation, coupled with expression microarrays, to identify novel targets of epigenetic silencing in glioma cell lines. From this analysis, we identified &amp;gt;160 genes up-regulated by 5-aza-2′-deoxycytidine and trichostatin A treatment. Further characterization of 10 of these genes, including the putative metastasis suppressor CST6, the apoptosis-inducer BIK, and TSPYL5, whose function is unknown, revealed that they are frequent targets of epigenetic silencing in glioma cell lines and primary tumors and suppress glioma cell growth in culture. Furthermore, we show that other members of the TSPYL gene family are epigenetically silenced in gliomas and dissect the contribution of individual DNA methyltransferases to the aberrant promoter hypermethylation events. These studies, therefore, lay the foundation for a comprehensive understanding of the full extent of epigenetic changes in gliomas and how they may be exploited for therapeutic purposes. (Cancer Res 2006; 66(15): 7490-501)
Effect of remodelling, stretch and ischaemia on ventricular fibrillation frequency and dynamics in a heart failure model
Authors: J MORENO, A ZAITSEV, M WARREN, O BERENFELD, J KALIFA, E LUCCA, S MIRONOV, P GUHA, J JALIFE
Journal: Cardiovascular Research (2004)

The dynamics of ventricular fibrillation (VF) in the presence of heart failure (HF) are different from those in the normal heart. This has been attributed solely to HF-induced electrophysiologic remodelling. We hypothesized that acute stretch and ischaemia, which are normally present during VF, might contribute significantly to the altered VF dynamics in HF.HF was induced in eight sheep by rapid ventricular pacing for 4-6 weeks. Eight sheep served as controls. Optical mapping of isolated hearts was performed during VF at low intraventricular pressure (0-5 mm Hg), high pressure (25-30 mm Hg, in six HF and six controls), and at low pressure after 5 min of global ischaemia (six HF, five controls). Maximum dominant frequency (DF(max)), singularity point (SP) density and number of SP lasting more than one revolution (rotors) were analyzed. Possible statistical interactions between HF and ischaemia (HF x ischaemia) or stretch (HF x stretch) were evaluated.At low pressure, VF in HF was slower (13% reduction in DF(max)) and more organized than in control: 33% less SPs and 74% less rotors with 20% longer life spans. Acute stretch did not affect DF(max) but increased SP and rotors density similarly in both groups (no interaction HF x stretch). In controls, ischaemia caused a marked decrease in DF(max), SP density and incidence of rotors. However, in HF animals, the ischaemia-induced decrease in SP density was virtually abolished, indicating a significant interaction HF x ischaemia (p<0.005).HF remodelling decreases VF rate and increases VF organization. Acute stretch partially reverses these effects by a mechanism that is independent of remodelling. The effects of acute ischaemia on VF dynamics are significantly attenuated in HF compared to normal hearts.
OBSERVATIONS ON THE INFECTION OF CHICK EMBRYOS WITH BACTERIUM TULARENSE, BRUCELLA, AND PASTEURELLA PESTIS
Authors: G. John Buddingh, Frank C. Womack
Journal: The Journal of Experimental Medicine (1941)

1. Comparison of the infections of chick embryos by the chorio-allantoic route indicates that Bacterium tularense and Brucella suis, abortus, and melitensis exhibit varying degrees of facultative intracellular parasitism. Pasteurella pestis is adapted to rapid proliferation and spread in the intercellular fluids. 2. In the early stages of infection Bacterium tularense has a marked affinity for growth within ectodermal epithelial cells. Brucella suis and Brucella abortus differ in their selectivity for cells of mesodermal derivation and especially in their effect on vascular endothelium. The strain of Brucella melitensis studied is limited in its intracellular growth to ectodermal epithelium. 3. Many of the features characteristic of these infections in the natural hosts are reproduced in the chick embryo and its membranes. 4. The possible implications regarding the differences in behavior of these microorganisms in relation to the problem of infection and pathogenesis of these diseases are discussed.
Self-injection of dermal filler: an underdiagnosed entity?
Authors: N. Raoof, S.M. Salvi
Journal: British Journal of Dermatology (2014)

Dermal fillers are increasingly used by clinicians (and nonclinicians) in patients requiring facial rejuvenation, as well as for other aesthetic uses such as treatment of age-related wrinkles, skin folds and depressed scars. We report the case of a patient who injected herself with dermal filler purchased over the internet and who required intervention for the undesired effect. We would like to highlight the ease with which these devices can be purchased over the internet, the risks they pose and the necessity of regulating their administration.
Treatment of severe neurological deficits with IgG depletion through immunoadsorption in patients with Escherichia coli O104:H4-associated haemolytic uraemic syndrome: a prospective trial
Authors: Andreas Greinacher, Sigrun Friesecke, Peter Abel, Alexander Dressel, Sylvia Stracke, Michael Fiene, Friedlinde Ernst, Kathleen Selleng, Karin Weissenborn, Bernhard MW Schmidt, Mario Schiffer, Stephan B Felix, Markus M Lerch, Jan T Kielstein, Julia Mayerle
Journal: The Lancet (2011)
Endogenous Antispermatogenic Agents: Prospects for Male Contraception
Authors: L L Ewing, B Robaire
Journal: The Annual Review of Pharmacology and Toxicology (1978)

A review of endogenous antispermatogenic agents as prospects for male contraception is reported. It is demonstrated that endogenous compounds exert regulatory influences at 4 major levels in the male: 1) between germ cells; 2) between Sertoli and germ cells; 3) between Leydig cells and seminiferous tubules; and 4) between the central nervous system and the testis. Efforts to interrupt spermatogenesis have failed to find application as male contraceptives for various reasons: 1) some investigators ignored the vulnerable control points by utilizing nonspecific agents; 2) others attacked a vulnerable control point but used synthetic drugs that had deleterious side effects; and 3) still others attacked a vulnerable control point with a relatively innocuous drug but used an impractical mode of drug administration. The potential for devising innovative techniques for administering relatively innocuous drugs at dosages sufficient to produce sterility without causing deleterious side effects is demonstrated. The most promising solution for the development of an antispermatogenic male contraceptive is the interference with the adenohypophyseal-gonadal axis via the subcutaneous sustained release of steroid formulations containing either androgen-danazol, androgen-progestin, or androgen-estrogen formulations. Another promising agent would be luteinizing releasing hormone agonist-androgen formulation.
Identification of BACE2 as an avid ß-amyloid-degrading protease
Authors: Samer O Abdul-Hay, Tomoko Sahara, Melinda McBride, Dongcheul Kang, Malcolm A Leissring
Journal: Molecular Neurodegeneration (2012)

Proteases that degrade the amyloid ß-protein (Aß) have emerged as key players in the etiology and potential treatment of Alzheimer's disease (AD), but it is unlikely that all such proteases have been identified. To discover new Aß-degrading proteases (AßDPs), we conducted an unbiased, genome-scale, functional cDNA screen designed to identify proteases capable of lowering net Aß levels produced by cells, which were subsequently characterized for Aß-degrading activity using an array of downstream assays.The top hit emerging from the screen was ß-site amyloid precursor protein-cleaving enzyme 2 (BACE2), a rather unexpected finding given the well-established role of its close homolog, BACE1, in the production of Aß. BACE2 is known to be capable of lowering Aß levels via non-amyloidogenic processing of APP. However, in vitro, BACE2 was also found to be a particularly avid AßDP, with a catalytic efficiency exceeding all known AßDPs except insulin-degrading enzyme (IDE). BACE1 was also found to degrade Aß, albeit ~150-fold less efficiently than BACE2. Aß is cleaved by BACE2 at three peptide bonds-Phe19-Phe20, Phe20-Ala21, and Leu34-Met35--with the latter cleavage site being the initial and principal one. BACE2 overexpression in cultured cells was found to lower net Aß levels to a greater extent than multiple, well-established AßDPs, including neprilysin (NEP) and endothelin-converting enzyme-1 (ECE1), while showing comparable effectiveness to IDE.This study identifies a new functional role for BACE2 as a potent AßDP. Based on its high catalytic efficiency, its ability to degrade Aß intracellularly, and other characteristics, BACE2 represents a particulary strong therapeutic candidate for the treatment or prevention of AD.
Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning
Authors: Weixiang Guo, Andrea M Allan, Ruiting Zong, Li Zhang, Eric B Johnson, Eric G Schaller, Adeline C Murthy, Samantha L Goggin, Amelia J Eisch, Ben A Oostra, David L Nelson, Peng Jin, Xinyu Zhao
Journal: Nature Medicine (2011)
Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program
Authors: John M. Kane, Delbert G. Robinson, Nina R. Schooler, Kim T. Mueser, David L. Penn, Robert A. Rosenheck, Jean Addington, Mary F. Brunette, Christoph U. Correll, Sue E. Estroff, Patricia Marcy, James Robinson, Piper S. Meyer-Kalos, Jennifer D. Gottlieb, Shirley M. Glynn, David W. Lynde, Ronny Pipes, Benji T. Kurian, Alexander L. Miller, Susan T. Azrin, Amy B. Goldstein, Joanne B. Severe, Haiqun Lin, Kyaw J. Sint, Majnu John, Robert K. Heinssen
Journal: American Journal of Psychiatry (2015)

Objective: The primary aim of this study was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for implementation in the U.S. health care system, with community care on quality of life. Method: Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and ≤6 months of antipsychotic treatment (N=404) were enrolled and followed for ≥2 years. The primary outcome was the total score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in regular activities. Results: The 223 recipients of NAVIGATE remained in treatment longer, experienced greater improvement in quality of life and psychopathology, and experienced greater involvement in work and school compared with 181 participants in community care. The median duration of untreated psychosis was 74 weeks. NAVIGATE participants with duration of untreated psychosis of <74 weeks had greater improvement in quality of life and psychopathology compared with those with longer duration of untreated psychosis and those in community care. Rates of hospitalization were relatively low compared with other first-episode psychosis clinical trials and did not differ between groups. Conclusions: Comprehensive care for first-episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes. Effects are more pronounced for those with shorter duration of untreated psychosis.
Angiotensin-Converting Enzyme Inhibition and Renal Protection in Nondiabetic Patients
Authors: Carlos Chiurchiu, Giuseppe Remuzzi, Piero Ruggenenti
Journal: Journal of the American Society of Nephrology (2005)

ESRD represents a major health problem. The number of patients who enter kidney replacement programs has increased at an average of 7% per year in the past 10 yr. A large number of experimental and clinical studies have demonstrated that chronic nephropathies share common pathogenic mechanisms that contribute to renal disease progression, even independent of the original cause. Clinical studies found a significant correlation between the extent of urinary protein excretion and the rate of GFR decline in both diabetic and nondiabetic chronic nephropathies. Randomized trials, in particular the Ramipril Efficacy In Nephropathy (REIN) study, also showed that treatments that reduce proteinuria (namely angiotensin-converting enzyme [ACE] inhibitors) are renoprotective and limit progression to ESRD. Meta-analyses of randomized clinical trials also evaluated the role of proteinuria and of ACE inhibition therapy in chronic renal disease progression. Their findings were consistent with those of the REIN study and confirmed in larger series of patients the predictive value of proteinuria and the renoprotective effect of proteinuria reduction by ACE inhibition therapy. Thus, the meta-analyses may confirm and extend previous findings generated by randomized clinical trials. Conceivably, well-designed studies in properly selected and carefully monitored patients who are at increased risk continue to be the best approach to test novel hypotheses. The meta-analyses, however, represent a valuable tool to evaluate the consistency and generalizability of trial results to larger cohorts of patients.
Cerebellar Purkinje units – basic functional elements of movement control
Authors: Gilbert A. Chauvet
Journal: Behavioral and Brain Sciences (1997)

Braitenberg et al.'s target article presents the best current integration of anatomical and physiological data, and provides a qualitative description of cerebellar function in terms of the dynamics of processes based on the geometry of the cerebellar cortex. We compare the proposed model to our own quantitative model based on the concept of Purkinje unit.
Dominant T- and B-cell epitopes in an autoantigen linked to Chagas’ disease
Authors: Núria Gironès, Clara I. Rodríguez, Eugenio Carrasco-Marín, Reyes Flores Hernáez, Jacobo López de Rego, Manuel Fresno
Journal: Journal of Clinical Investigation (2001)

In Chagas' disease caused by Trypanosoma cruzi, a paradigm of autoimmune disease, both autoantibodies and autoreactive T cells have been described. We have identified a novel dominant autoantigen, named Cha, recognized by the majority of sera from T. cruzi–infected humans and mice. We noted significant homologies between amino acids 120-129 of Cha, where the B-cell epitope maps, and an expressed sequence tag from T. cruzi, and also between amino acids 254-273 of Cha and a repeated amino acid sequence from the shed acute-phase antigen (SAPA) of T. cruzi. Moreover, T. cruzi–infected mice contain autoreactive T cells that can cross-react with Cha and the SAPA homologous peptides. Transfer of T cells from infected mice triggered anti-Cha (120-129) Ab production in naive recipients. Interestingly, heart tissue sections from those adoptive transferred mice showed cardiac pathology similar to T. cruzi–infected mice. Our results demonstrate the presence of both T- and B-cell cross-reactive epitopes in the Cha antigen. This dual mimicry may lead to T/B cell cooperation and give rise to a pathological immunodominant response against Cha in T. cruzi infected animals.
Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases
Authors: N C Tebbutt
Journal: Gut (2003)

The role of palliative resection of the primary tumour in patients who present with metastatic colorectal cancer is unclear.This study compared the incidence of major intestinal complications in such patients who received chemotherapy treatment with or without prior palliative resection of the primary tumour.The incidence of intestinal obstruction, perforation, fistula formation, and gastrointestinal haemorrhage, and the requirement for abdominal radiotherapy in patients with metastatic colorectal cancer treated at a single institution over a 10 year period was determined.Eighty two patients received initial treatment with chemotherapy without resection of the primary tumour (unresected group) and 280 patients had undergone prior resection (resected group). In the unresected group, the incidence of peritonitis, fistula formation, and intestinal haemorrhage was 2.4% (95% confidence interval (CI) 0.3-8.5%), 3.7% (95% CI 0.8-10.3%), and 3.7% (95% CI 0.8-10.3%), respectively, and was not significantly different from the resected group. Intestinal obstruction affected 13.4% (95% CI 6.9-22.7%) of patients in the unresected group and 13.2% (95% CI 9.2-17.2%) of patients in the resected group. More patients in the unresected group required >/=3 blood transfusions (14.6% v 7.5%; p=0.048) and abdominal radiotherapy (18.3% v 9.6%; p=0.03) than the resected group.The incidence of major intestinal complications in patients with unresected colorectal cancer and synchronous metastases who receive initial treatment with chemotherapy is low. Chemotherapy may be successfully used as initial treatment for such patients with no increased risk of most major intestinal complications compared with patients who have undergone initial resection of the primary tumour.