tbuckley/cabot-search huggingface dataset:
Brief Report: Prevalence of Antineutrophil Cytoplasmic Antibodies in Infective Endocarditis
Authors: Alfred Mahr, Frédéric Batteux, Sarah Tubiana, Claire Goulvestre, Michel Wolff, Thomas Papo, François Vrtovsnik, Isabelle Klein, Bernard Iung, Xavier Duval
Journal: Arthritis & Rheumatology (2014)

Infective endocarditis (IE) mimics primary systemic vasculitis, and there are sporadic reports of positivity for antineutrophil cytoplasmic antibodies (ANCAs) among patients with IE. Because the frequency of ANCAs in IE is unknown, this study was undertaken to assess the seroprevalence of ANCAs in a large number of patients with IE.The study was conducted in the framework of a single-center prospective cohort study of incident IE cases. Demographic, clinical, laboratory, and microbiologic data were collected, and magnetic resonance imaging of the brain was performed at diagnosis. For those patients whose serum had been stored at diagnosis, ANCAs were assessed by indirect immunofluorescence assay in ethanol-, formalin-, and methanol-fixed neutrophils. In addition, ANCA specificity for proteinase 3 (PR3) and myeloperoxidase (MPO) was assessed by enzyme-linked immunosorbent assay. Rheumatoid factor (RF), antinuclear antibodies (ANAs), anticardiolipin antibodies (aCL), and serum Ig levels were also measured. Comparisons between groups were made using Wilcoxon's rank sum and chi-square or Fisher's exact tests.Among 109 patients with IE, 18% had cytoplasmic ANCAs (cANCA) and/or perinuclear ANCAs (pANCA) and 8% had PR3-ANCAs or MPO-ANCAs, some with very high titers. Positivity for both cANCA or pANCA and PR3-ANCAs or MPO-ANCAs was found in 6% of patients, and RF, ANAs, and aCL were detected in 35%, 16%, and 23% of samples, respectively. No consistent clinical pattern of IE was observed in the anti-PR3/anti-MPO-positive IE patients, whereas positivity for cANCA/pANCA was associated with younger age (P = 0.022), more frequent occurrence of echocardiographic vegetations (P = 0.043), and above-normal serum IgG levels (P = 0.017).ANCAs, including PR3- and MPO-ANCAs, occur in a substantial proportion of patients with IE. The link between cANCA/pANCA and specific features of IE requires further study.
Ventricular Late Potentials in Myotonic Dystrophy
Authors: Mark R. Milner, Rollin J. Hawley, Mark Jachim, Joseph Lindsay, Ross D. Fletcher
Journal: Annals of Internal Medicine (1991)

To determine the prevalence of ventricular late potentials, as determined by signal-averaged electrocardiography, in patients with myotonic dystrophy.Cross sectional, with blinded analysis of all electrocardiographic data.Outpatient departments of a Veterans Affairs medical center and a tertiary care private hospital.Twenty-four patients with myotonic dystrophy. Patients were excluded from the study if they had either a history suggestive of significant ventricular arrhythmias or electrocardiographic evidence of a bundle-branch block. Two comparison groups were also formed; one group included 44 healthy employees at the tertiary hospital and the other, 30 cardiac patients with inducible ventricular tachycardia.A time-domain analysis of the signal-averaged electrocardiograms showed that 75% of patients with myotonic dystrophy met one criterion for the presence of late potentials, 67% met two criteria, and 29% met all three criteria. Spectrotemporal mapping in these patients showed markedly abnormal spectral peaks with a mean factor of normality that was significantly lower than that of the normal volunteers; the frequency of electrocardiographic abnormalities approached that seen in patients with known ventricular tachycardia. The presence of late potentials correlated directly with the length of the PR interval and inversely with left ventricular fractional shortening.In our study, the prevalence of late potentials on signal-averaged electrocardiography in patients with myotonic dystrophy approached that seen in cardiac patients with inducible ventricular tachycardia. It is possible that ventricular arrhythmias play a role in the occurrence of sudden death in some patients with myotonic dystrophy.
Interstitial granulomatous dermatitis: a distinct entity with characteristic histological and clinical pattern
Authors: A. Peroni, C. Colato, D. Schena, P. Gisondi, G. Girolomoni
Journal: British Journal of Dermatology (2011)

Interstitial granulomatous dermatitis (IGD) is a rare disease for which a clinical-pathological correlation is essential to establish diagnosis.To describe the histological and clinical features of patients with IGD seen in our department from 2004 to 2010, and to undertake a literature review and critical analysis of additional cases.Twelve adult patients (nine women and three men; mean age 58·5 years; range 32-73 years) with IGD were enrolled. Lesions consisted of asymptomatic erythematous papules and plaques, symmetrically distributed on the trunk and the proximal limbs. Two patients had skin-coloured papules. Six patients had articular involvement (arthralgias, spondyloarthritis, rheumatoid arthritis) and three patients had cancer.All cases showed a predominant CD68-positive macrophage infiltrate distributed between collagen bundles of the mid- and deep dermis. Macrophages were also surrounding degenerated collagen fibres. A few neutrophils and/or eosinophils were also present. No vasculitis or significant mucin deposition was observed. Of the 62 cases of IGD reported since 1993, 53 fulfilled stringent diagnostic criteria. Erythematous papules and plaques on the trunk and proximal limbs were the dominant manifestation. Approximately 10% of patients had cord-like lesions. More than 50% of patients with IGD had arthralgia or arthritis, and less commonly other rheumatic disorders. Disease duration is months to years, but long-term prognosis seems favourable.IGD is a distinct entity with a typical histological and clinical pattern. The importance and the nature of the association with extracutaneous diseases remains to be clarified. Patients should be screened for rheumatic and autoimmune diseases.
Abstract P452: Pathway Analysis Of One-carbon Metabolism In Association With Acute Myocardial Infarction In Patients With Stable Angina Pectoris
Authors: Yunpeng Ding, Gard F Svingen, Eva K Pedersen, Åse Fredriksen, Hall Schartum-Hansen, klaus Meyer, Per M Ueland, Ottar Nygård
Journal: Circulation (2014)

Background: One-carbon metabolism (OCM) is involved in RNA, DNA synthesis and in epigenetic regulation. Pathway gene analysis is more likely to capture potential gene-disease associations comparing to single gene analysis. We investigated whether genetic variants in folate network as well as their interactions would predict subsequent acute myocardial infarction (AMI) in patients undergoing elective coronary angiography for stable angina pectoris (SAP). Methods: A total of 2381 subjects (98% Caucasian) recruited to the Western Norway B Vitamin Intervention Trial (WENBIT) in 2000-2004 were studied. Patients were followed until a subsequent AMI or end of 2006. We genotyped 18 commonly investigated single nucleotide polymorphisms (SNPs) in 13 genes in the OCM network. Predictable variants were selected based on both out-of-bag importance scores from random survival forests and their incremental effects from recursive nested analysis. We then assessed gene-gene interactions among those predictive variants with generalized logistic model and calculated hazard ratio (HR), confidence interval (CI) for each predictor in Cox proportional hazard models. Results: There are 204 (8.57%) patients who experienced an AMI throughout 4.9 years (median) follow-up. We observed no violation from Hardy-Weinberg equilibrium in 15 SNPs in our population. Four SNPs (rs1076991, rs1021737, rs1801133 and rs3733890) in folate network were identified as promising candidates for predicting AMI risk. Interestingly, only rs1076991 associated significantly with AMI (HR=1.30, 95% CI: 1.10-1.52), indicating the other SNPs primarily mediate their risk bygene-gene interactions. There was a strong and stable interaction between the dominant model of rs3733890 and dominant model of rs34489327 (P for interaction: 0.003; HR =2.23, 95% CI: 1.27-3.92, adjusted for age, gender, smoking, diabetes mellitus, hypertension, extent of CAD by angiography (0-3), apolipoprotein (Apo) A1 and B, left ventricular ejection fraction and estimated glomerular filtration rate). Further adjustment for vitamins involved in OCM (folate, B2, B6, B12), the substrates (betaine and homocysteine) and products (methionine and dimethylglycine) of the betaine--homocysteine S-methyltransferase (BHMT) had minimal influence on the estimate. Conclusions: Prior studies show that BHMT transcription is associated with co-transcription of Apo B and that the rs3733890 of this gene is associated with higher dimethylglycine levels. We have recently shown that elevated plasma dimethylglycine is associated with increased risk of AMI and improves risk prediction in patients with SAP independent of Apo B levels. The current investigation extends previous knowledge, suggesting that a genetic variant in BHMT may modulate the risk of AMI by interfering with thymidylate synthesis independent of plasma dimethylglycine.
Abstract 4032: Targeting the isoprenoid biosynthetic pathway in a murine model of metastatic prostate cancer
Authors: Jacqueline E. Reilly, Jeffrey D. Neighbors, Nadine Bannick, Michael D. Henry, Craig H. Kuder, Raymond J. Hohl
Journal: Cancer Research (2014)

Abstract The isoprenoid biosynthetic pathway (IBP) provides substrates for the post-translational modification of key proteins in regulating malignant cell properties, including proliferation, migration, and invasion. Several studies have found broad inhibitors of the IBP, such as statins, to significantly reduce the risk of advanced prostate cancer (PCa), potentially through their induced-reduction of geranylgeranylated proteins. However, such inhibition of the entire IBP is limited by side effects resulting from depletion of all isoprenoids and their products. We have developed a novel compound, geranylgeraniol bisphosphonate (GGOHBP), selectively targeting geranylgeranyl diphosphate synthase (GGDPS) and reducing the post-translational modification of geranylgeranylated proteins. Luciferase-expressing human-derived 22Rv1 PCa cells were injected into the left ventricle of 20 mice using bioluminescence imaging (BLI) to visualize tumor development. After three weeks 18/20 mice had developed tumors and daily subcutaneous (SQ) injections of 1.5mg/kg GGOHBP were given for one month. All 18 mice developed mandible tumors, 13 developed adrenal gland tumors, 4 developed intestinal tumors, 2 developed femoral tumors, 2 developed liver tumors, and 1 developed a tumor in an unidentified location in the chest cavity. Ex vivo photon count analyses revealed an 80% (p=0.1458) reduction in adrenal gland tumors of the treated mice as compared to vehicle-treated controls. This corresponded to a 54% (p=0.0007) reduction in total adrenal gland tumor weight in the treated as compared to the control mice. Western blot analysis of the adrenal gland tumors and one intestinal tumor showed a reduction in Rap1A geranylgeranylation in the treated mice and not the control mice, while non-tumorous tissues showed no Rap1A alteration. A follow-up study of non-tumor bearing mice given SQ injections of 1.25 or 1.5 mg/kg GGOHBP daily did not reveal alterations in Rap1A geranylgeranylation in the adrenal glands, kidneys, liver, or heart. Our findings detail a novel compound capable of preferentially altering the IBP in the adrenal gland tumors of a murine model of metastatic PCa. Future work defining the mechanism behind this focal effect and the adrenal gland isoprenoid environment will allow compound optimization and further understanding of the IBP's role in PCa metastasis. Citation Format: Jacqueline E. Reilly, Jeffrey D. Neighbors, Nadine Bannick, Michael D. Henry, Craig H. Kuder, Raymond J. Hohl. Targeting the isoprenoid biosynthetic pathway in a murine model of metastatic prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4032. doi:10.1158/1538-7445.AM2014-4032
Outcome of congenital diaphragmatic hernia (CDH) in a non-ECMO unit
Authors: Chetan Pandit, Karen Walker, Robert Halliday, Rosemary Douglas, Nadia Badawi, Dominic Fitzgerald
Journal: European Respiratory Journal (2011)

Introduction: CDH management involves gentle ventilation, hypercarbia, iNO & delayed surgery. ECMO use is limited & associated with greater neurodevelopmental sequelae.

Aim: Study mortality and neurological morbidity of CDH patients at 12 months of age from a tertiary level non-ECMO unit.

Methods: Retrospective review of all CDH neonates presenting to the Children's Hospital at Westmead over 5 years [01/2005 to 12/2009]. Infants were assessed at 1 year using the Bayley Scales of Infant and Toddler Development, Version III. Visual reward orientation audiometry was performed.

Results: Of 37 babies [M=17] referred, 5 [13%] died perioperatively, 6 lost to follow-up & 2 missed developmental review. 30/32 [93%] of the survivors were seen at 1 year and 24/32 [75%] had a neurodevelopmental assessment. Mean GA 37.9 wks (SD ±1.7) & BW 2983gm (± 722.5). CDH diagnosed: 17 antenatal ultrasound [US] < 22 weeks of gestation, 6 later antenatal US and 14 [44%] postnatally. Median age at surgery was 7 days (range 0 to 55). 8 (21%) had an associated cardiac anomaly [4 had surgery]. Below average outcomes in 2 (8%) infants on cognitive skills & expressive language; 6 (23%) receptive language, 7 (27%) in gross motor skills & 2 (8%) deficient in fine motor skills. No sensorineural hearing deficits. Neither mortality nor abnormal neurodevelopmental outcome were significantly associated with prematurity, gender, time of diagnosis, pneumothorax, type of closure and oxygen at discharge.

Conclusion: Mortality rates in a tertiary level non-ECMO unit are comparable with ECMO centres and 1 year neuro-morbidity is lower. The outcome from conventional strategies is comparable in the treatment of most CDH patients where ECMO is not available.
Activation of GPCRs modulates quantal size in chromaffin cells through Gβγ and PKC
Authors: Xiao-Ke Chen, Lie-Cheng Wang, Yang Zhou, Qian Cai, Murali Prakriya, Kai-Lai Duan, Zu-Hang Sheng, Christopher Lingle, Zhuan Zhou
Journal: Nature Neuroscience (2005)
Bioreducible poly(2-ethyl-2-oxazoline)–PLA–PEI-SS triblock copolymer micelles for co-delivery of DNA minicircles and Doxorubicin
Authors: Vítor M. Gaspar, Patrick Baril, Elisabete C. Costa, Duarte de Melo-Diogo, Frédéric Foucher, João A. Queiroz, Fani Sousa, Chantal Pichon, Ilídio J. Correia
Journal: Journal of Controlled Release (2015)
Garlic Prevents Plaque . . .
Authors: Brian Vastag
Journal: JAMA (2002)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Judge orders GPs to hand over patient records
Authors: Clare Dyer
Journal: BMJ (2001)

A High Court judge has ordered the partners in an NHS general practice to hand over confidential records of patients and other documents to their local health authority, so it can investigate concerns about their practice.

Mr Justice Munby made the order this month in a judgment that was given in public but with anonymity for all parties, including the health authority. The health authority was contacted by a local authority that had brought care proceedings over children who were patients of the general practice. A number of other people, now adults, also involved in the proceedings (some only indirectly) were also …
Abstract 138: Novel PAK4 allosteric modulators (PAMs) provide potential therapeutic options in human gastric cancer
Authors: Wenwen Chien, Jinfen Xiao, Ling-Wen Ding, Muhammad Ikhsan B. Muzakar, Qiao-Yang Sun, Sigal Gery, William Senapedis, Sharon Shacham, Erkan Baloglu, H. Phillip Koeffler
Journal: Cancer Research (2015)

Abstract Expression of PAK4 (p21-activated serine/threonine kinase 4) is associated with gastric tumorigenesis. Overexpression of PAK4 is correlated with metastasis of gastric cancer and in part confers cisplatin resistance in gastric cancer patients. We transduced the human gastric cancer cell line AGS with CRISPR/cas9 targeting PAK4, and observed reduced cell proliferation and motility. Novel PAK4 allosteric modulators (PAMs) were evaluated for their potential therapeutic use for gastric cancer. A panel of human gastric cancer cell lines was screened with four PAMs (KPT-7189, -7349, -7657, -8752). MTS assay showed inhibition of cell viability by PAMs in 6 of 10 gastric cancer cell lines (IC50 ranged from 50 to 5000 nM). Cell cycle analysis and annexin V assay indicated a combination of cell growth arrest at G1 phase and cell apoptosis after treatment with PAMs. Furthermore, PAMs diminished expression levels of PAK4, induced apoptosis-related molecule caspase-3, and suppressed PI3K/Akt and MEK/Erk signaling. Wound assay showed inhibition of cell migration and soft agar assay demonstrated suppression of colony formation for gastric cancer cells treated with PAMs. Mouse xenograft models are currently under investigation. Remarkably, PAMs in combination with cisplatin induced cell death in cisplatin-resistant gastric cancer cells in a synergistic manner. This study demonstrates PAMs have anti-tumor activity against gastric cancer cells and suggests their potential use for the treatment of gastric cancer. Citation Format: Wenwen Chien, Jinfen Xiao, Ling-Wen Ding, Muhammad Ikhsan B. Muzakar, Qiao-Yang Sun, Sigal Gery, William Senapedis, Sharon Shacham, Erkan Baloglu, H. Phillip Koeffler. Novel PAK4 allosteric modulators (PAMs) provide potential therapeutic options in human gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 138. doi:10.1158/1538-7445.AM2015-138
Progesterone and Preterm Delivery — Déjà Vu All Over Again
Authors: Michael F. Greene
Journal: New England Journal of Medicine (2003)

It has become almost a platitude to lament the complexity and intractability of the problem of preterm delivery, the poor predictive value of screening tests for its occurrence, its resistance to attempted interventions, and its increasing rate.1 Preterm delivery is more common among blacks, the poor, the unmarried, cigarette smokers, underweight women, women with multiple gestations, women with uterine anomalies, women with a history of previous preterm delivery, and women without prenatal care. Although the perinatal mortality rate due to prematurity has decreased dramatically during the past three decades, this reduction has resulted from improvements in perinatal and pediatric care . . .
Placental Angiogenic and Growth Factors in the Treatment of Chronic Varicose Ulcers: Preliminary Communication
Authors: H Burgos, A Herd, J P Bennett
Journal: Journal of the Royal Society of Medicine (1989)

A short-term clinical study on the effect of purified angiogenic and growth factors from human term placenta in the treatment of chronic varicose ulcers was carried out in 18 patients. Patients were randomly allocated to receive a maximum of two dressings containing or not containing these factors. The amount of granulation and epithelial tissue was clinically estimated 48 hours after each application. Patients treated with placental angiogenic and growth factors showed increased granulation and epithelial tissue. These results indicate that placental factors may be used for acceleration of wound healing.
608. VAI Deleted Adenovirus as an Oncolytic Agent Targeting Human EBV-Associated Tumours
Authors: Yaohe Wang, Shao-an Xue, Gunnel Hallden, Jennelle Francis, Beverly E. Griffin, Nick R. Lemoine
Journal: Molecular Therapy (2004)

The EBV genome is frequently present in Burkitt's lymphomas, B-Cell lymphomas of immunocompromised patients, nasopharyngeal carcinomas, Hodgkin's disease, T-cell lymphomas, natural killer cell leukemia/lymphoma, smooth-muscle tumors and gastric cancer. More recently, there have been scattered reports linking EBV with conventional epithelial cancers of other primary sites including breast cancers, lung cancers, prostate cancers, liver cancers, colon cancers and lymphoepithelioma-like carcinoma of the esophagus. Given the ever-growing number of tumor types associated with EBV infection, it is therefore critically important to develop therapeutic strategies to treat EBV-associated tumors. Replication-selective oncolytic adenovirus is a promising new platform for anti-cancer therapy. Data from numerous clinical trials have demonstrated several attenuated oncolytic viral mutants to be safe and to replicate selectively in tumor cells with significant anti-tumor potency. Virus associated (VA) 1 and 2 RNA are two low molecular weight adenoviral RNAs that are synthesized late during the viral replication cycle and are required for efficient translation of late viral mRNAs. When the VA1 gene is deleted, replication is impeded in most cells (including HEK 293 cells). The Epstein Barr Virus (EBV) genome encodes two small, non-polyadenylated nuclear RNAs (EBER 1 and 2) that are uniformly expressed in most EBV-associated human tumors. EBER 1 and 2 can functionally substitute for the VA1 RNAs of adenovirus, enabling replication to proceed normally through complementation of VA1 deletion mutants. We hypothesized that VA1-deleted adenovirus would selectively replicate in EBV-positive tumor cells due to complementation by EBER 1, with poor or no replication in normal cells and EBV-negative tumor cells. Our data demonstrate that cytotoxicity of VA1 RNA deletion mutants was restricted to EBV-positive tumor cells (e.g. c666, AGS-EBV, Raji, Jiyoye). Cytopathic effects were much lower in EBV-negative tumor cells (Hep-2, AGS-ATCC, Panc-1). The replication of the VA1 deletion mutant virus was 14–25 times higher in EBV-positive tumor cells than in EBV-negative tumor cells and comparable with wild type adenovirus. The VA1 mutant did not replicate in normal cells in culture such as normal human bronchial epithelial cells (NHBE), and replicated poorly in prostate epithelial cells (PrEC). In vivo, VAI deleted adenovirus showed the same efficacy as wild type adenovirus in xenograft models of human EBV-positive tumor cells, but much lower cytotoxicity than wildtype adenovirus. Our data suggest that a VA1 RNA-deleted viral mutant is a promising replication-selective oncolytic virus specifically targeting EBV-associated cancers.