tbuckley/cabot-search huggingface dataset:
Clinical significance of interleukin-6 measurement in early rheumatoid arthritis: relation with laboratory and clinical variables and radiological progression in a three year prospective study.
Authors: M A van Leeuwen, J Westra, P C Limburg, P L van Riel, M H van Rijswijk
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To evaluate the clinical significance of interleukin-6 (IL-6) measurements in relation to laboratory and clinical measures of disease activity and radiological progression in early rheumatoid arthritis (RA). METHODS--A prospective study was performed in 51 patients with early RA during the first three years of the disease, with monthly clinical and laboratory assessments and biannual radiographs of the hands and feet. IL-6 was measured by enzyme linked immunosorbent assay (ELISA). Cross sectional (n = 51) and longitudinal (n = 20) correlations between plasma IL-6 concentrations and values of C reactive protein (CRP), serum amyloid A protein (SAA), erythrocyte sedimentation rate (ESR), haemoglobin (Hb), platelets, and joint scores were calculated, and correlations made between time integrated values of IL-6, CRP and ESR, and radiological progression over three years (n = 20). RESULTS--Significant correlations were found between IL-6 and the acute phase response and platelets, but variable results were obtained for the correlation between IL-6 and Hb. In contrast to a significant correlation between time integrated values of CRP or ESR and radiological progression, time integrated values of IL-6 did not correlate with radiological progression over three years follow up. CONCLUSION--The course of disease activity and the radiological progression of joint damage are better reflected by CRP, SAA, and ESR values than by plasma IL-6 concentrations, particularly in stages of low disease activity.
AN EPITOME OF THE NEW SPECIFIC TREATMENT FOR SYPHILIS
Authors: J. E. R. McDONAGH
Journal: British Journal of Dermatology (1910)

Journal Article AN EPITOME OF THE NEW SPECIFIC TREATMENT FOR SYPHILIS Get access J. E. R. McDONAGH, F.R.C.S. J. E. R. McDONAGH, F.R.C.S. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 22, Issue 8, 1 August 1910, Pages 260–263, https://doi.org/10.1111/j.1365-2133.1910.tb16637.x Published: 01 August 1910
OXYGEN CONSUMPTION IN DOGS AS INFLUENCED BY THE ALTERED METABOLISM OF DIABETES MELLITUS
Authors: Harold G. Danford, Robert D. Galvin, Akira Horita
Journal: Journal of Clinical Investigation (1956)

The question of the total energy production in the human diabetic has been studied extensively by Benedict and Joslin (1, 2) and by Allen and Du Bois (3). It generally has been agreed that energy metabolism in mild cases of diabetes is normal, and that in the more severe cases is found increased when determined on the basis of kilogram of body weight. The lack of a satisfactory standard of comparison between diabetic and nondiabetic subjects hampered much of the earlier work in this field and led to disagreement regarding interpretation of data. Benedict and Joslin (1, 2), using the Harris-Benedict prediction standard, reported increases in metabolic rate of diabetic subjects of between 15 and 20 per cent. Lusk (4) criticized these data and computed that the increase in metabolism did not exceed 5 per cent. With the general acceptance of the more valid Du Bois standard (5) comprehending body surface area, many of the earlier data ascribing an increase in metabolic rate to diabetes have been recalculated and shown to be erroneous. More recent publications likewise have been of conflicting nature reporting increases in metabolic rate as great as 40 per cent and decreases of 32 per cent in severe clinical diabetes mellitus (6-9). In the pancreatectomized dog, on the other hand, respiratory metabolism generally has been found to be increased (10-12). However, attempts at direct comparison between this type of acute canine diabetes and the disease as it occurs in humans is illogical in view of the typical alteration in fatty acid metabolism following pancreatectomy. We are not aware that oxidative metabolism has been measured previously in the alloxan diabetic animal which provides a metabolic defect more nearly identical with that occurring in human diabetes mellitus. That an increase in oxygen consumption in dia-
RNA-binding protein RBM20 represses splicing to orchestrate cardiac pre-mRNA processing
Authors: Henrike Maatz, Marvin Jens, Martin Liss, Sebastian Schafer, Matthias Heinig, Marieluise Kirchner, Eleonora Adami, Carola Rintisch, Vita Dauksaite, Michael H. Radke, Matthias Selbach, Paul J.R. Barton, Stuart A. Cook, Nikolaus Rajewsky, Michael Gotthardt, Markus Landthaler, Norbert Hubner
Journal: Journal of Clinical Investigation (2014)

Mutations in the gene encoding the RNA-binding protein RBM20 have been implicated in dilated cardiomyopathy (DCM), a major cause of chronic heart failure, presumably through altering cardiac RNA splicing. Here, we combined transcriptome-wide crosslinking immunoprecipitation (CLIP-seq), RNA-seq, and quantitative proteomics in cell culture and rat and human hearts to examine how RBM20 regulates alternative splicing in the heart. Our analyses revealed the presence of a distinct RBM20 RNA-recognition element that is predominantly found within intronic binding sites and linked to repression of exon splicing with RBM20 binding near 3' and 5' splice sites. Proteomic analysis determined that RBM20 interacts with both U1 and U2 small nuclear ribonucleic particles (snRNPs) and suggested that RBM20-dependent splicing repression occurs through spliceosome stalling at complex A. Direct RBM20 targets included several genes previously shown to be involved in DCM as well as genes not typically associated with this disease. In failing human hearts, reduced expression of RBM20 affected alternative splicing of several direct targets, indicating that differences in RBM20 expression may affect cardiac function. Together, these findings identify RBM20-regulated targets and provide insight into the pathogenesis of human heart failure.
Diagnosis and management of subclinical hypothyroidism in pregnancy
Authors: R. Negro, A. Stagnaro-Green
Journal: BMJ (2014)

In prospective studies, the prevalence of undiagnosed subclinical hypothyroidism in pregnant women ranges from 3% to 15%. Subclinical hypothyroidism is associated with multiple adverse outcomes in the mother and fetus, including spontaneous abortion, pre-eclampsia, gestational hypertension, gestational diabetes, preterm delivery, and decreased IQ in the offspring. Only two prospective studies have evaluated the impact of levothyroxine therapy in pregnant women with subclinical hypothyroidism, and the results were mixed. Subclinical hypothyroidism is defined as raised thyrotropin combined with a normal serum free thyroxine level. The normal range of thyrotropin varies according to geographic region and ethnic background. In the absence of local normative data, the recommended upper limit of thyrotropin in the first trimester of pregnancy is 2.5 mIU/L, and 3.0 mIU/L in the second and third trimester. The thyroid gland needs to produce 50% more thyroid hormone during pregnancy to maintain a euthyroid state. Consequently, most women on levothyroxine therapy before pregnancy require an increase in dose when pregnant to maintain euthyroidism. Ongoing prospective trials that are evaluating the impact of levothyroxine therapy on adverse outcomes in the mother and fetus in women with subclinical hypothyroidism will provide crucial data on the role of thyroid hormone replacement in pregnancy.
A Variant of the Anterior Opercular Syndrome With Supranuclear Gaze Palsy
Authors: Ashutosh P. Jadhav, Georgios Zenonos, Misha Pless, Tudor G. Jovin, Lawrence Wechsler
Journal: JAMA Neurology (2013)

A78-YEAR-OLDWOMAN withahistoryofdiabetes mellitus and hypertensionsought care because of sudden-onset dysarthria, left face and arm weakness, and right gaze preference. Shortly afterward, the patientdevelopedbilateralfacialweakness, with her gaze returning to the midline position. She had bilateral ptosis, near-total ophthalmoplegia, anarthria, and an inability to move her tongue and subsequently requiredintubationforairwayprotection. Attempts to extubate the patient were unsuccessful, and tracheotomy was necessary. Two weeks after presentation, the patient was alert and followed simple commands. She had relatively preservedstrengthinallextremitiesbut no change in profound bilateral facial weakness (Figure, D). She had limitedvolitionalabilitytomoveher eyes vertically (Figure, E and F) or horizontally. This could be overcome easily with oculocephalic maneuvers(Figure,G-J;Video,http:
A Hormone–DNA Repair Circuit Governs the Response to Genotoxic Insult
Authors: Jonathan F. Goodwin, Matthew J. Schiewer, Jeffry L. Dean, Randy S. Schrecengost, Renée de Leeuw, Sumin Han, Teng Ma, Robert B. Den, Adam P. Dicker, Felix Y. Feng, Karen E. Knudsen
Journal: Cancer Discovery (2013)

Abstract Alterations in DNA repair promote tumor development, but the impact on tumor progression is poorly understood. Here, discovery of a biochemical circuit linking hormone signaling to DNA repair and therapeutic resistance is reported. Findings show that androgen receptor (AR) activity is induced by DNA damage and promotes expression and activation of a gene expression program governing DNA repair. Subsequent investigation revealed that activated AR promotes resolution of double-strand breaks and resistance to DNA damage both in vitro and in vivo. Mechanistically, DNA-dependent protein kinase catalytic subunit (DNAPKcs) was identified as a key target of AR after damage, controlling AR-mediated DNA repair and cell survival after genotoxic insult. Finally, DNAPKcs was shown to potentiate AR function, consistent with a dual role in both DNA repair and transcriptional regulation. Combined, these studies identify the AR–DNAPKcs circuit as a major effector of DNA repair and therapeutic resistance and establish a new node for therapeutic intervention in advanced disease. Significance: The present study identifies for the first time a positive feedback circuit linking hormone action to the DNA damage response and shows the significant impact of this process on tumor progression and therapeutic response. These provocative findings provide the foundation for development of novel nodes of therapeutic intervention for advanced disease. Cancer Discov; 3(11); 1254–71. ©2013 AACR. See related commentary by Bartek et al., p. 1222 This article is highlighted in the In This Issue feature, p. 1207
Treatment of Indolent B-Cell Nonfollicular Lymphomas: Final Results of the LL01 Randomized Trial of the Gruppo Italiano per lo Studio dei Linfomi
Authors: Luca Baldini, Maura Brugiatelli, Stefano Luminari, Marco Lombardo, Francesco Merli, Stefano Sacchi, Paolo Gobbi, Marina Liberati, Luigi Cavanna, Mariangela Colombi, Caterina Stelitano, Maria Goldaniga, Fortunato Morabito, Massimo Federico, Vittorio Silingardi
Journal: Journal of Clinical Oncology (2003)

Purpose: To evaluate the effect of epirubicin on therapeutic response and survival in patients with indolent nonfollicular B-cell lymphomas (INFL) treated with pulsed high-dose chlorambucil. Patients and Methods: A total of 170 untreated patients with advanced/active INFL were randomly assigned to receive either eight cycles of high-dose chlorambucil (15 mg/m 2 /d) plus prednisone (100 mg/d) for 5 days (HD-CHL-P; arm A) or eight cycles of HD-CHL-P plus epirubicin 60 mg/m 2 intravenous on day 1 (arm B). The responding patients were randomly assigned to either maintenance therapy with interferon alfa (IFNα-2a; 3 MU, three times weekly) for 12 months or observation. Results: There were 160 assessable patients (82 males, 78 females; median age, 63 years; range, 33 to 77 years); 77 patients were assigned to arm A, and 83 were assigned to arm B. Induction therapy led to 47 complete responses (CRs; 29.4%) and 68 partial responses (PRs; 42.5%), with no significant difference between the two arms (60 CR + PR in arm A [77.9%] and 55 CR + PR in arm B [66.3%]; P = .07). After a median follow-up of 38 months (range, 2 to 103 months), there was no between-group difference in overall survival (OS; P = .45), failure-free survival (P = .07), or progression-free survival (PFS; P = .5). Eighty-eight patients were randomly assigned to either IFNα-2a (n = 43) or observation (n = 45), without any difference in 3-year PFS (44% and 42%, respectively). Univariate analysis showed that OS was influenced by age, anemia, serum lactate dehydrogenase levels, and International Prognostic Index distribution; multivariate analysis identified age and anemia as having influence on OS. Conclusion: HD-CHL-P treatment outcome in INFL patients was good (50% 3-year PFS, minimal toxicity, and low costs); epirubicin did not add any advantage. One-year IFNα maintenance treatment did not prolong response duration.
Lessons from Applied Ecology: Cancer Control Using an Evolutionary Double Bind
Authors: Robert A. Gatenby, Joel Brown, Thomas Vincent
Journal: Cancer Research (2009)

Abstract Because the metastatic cascade is largely governed by the ability of malignant cells to adapt and proliferate at the distant tissue site, we propose that disseminated cancers are analogous in many important ways to the evolutionary and ecological dynamics of exotic species. Although pests can be decimated through the application of chemical toxins, this strategy virtually never achieves robust control as evolution of resistant phenotypes typically permits population recovery to pretreatment levels. In general, biological strategies that introduce predators, parasitoids, or pathogens have achieved more durable control of pest populations even after emergence of resistant phenotypes. From this we propose that long term outcome from any treatment strategy for invasive pests, including cancer, is not limited by evolution of resistance, but rather by the phenotypic cost of that resistance. If a cancerous cell's adaptation to therapy is achieved by upregulating xenobiotic metabolism or a redundant signaling pathway, the required investment in resources is small, and the original malignant phenotype remains essentially intact. As a result, the cancer cells' initial high level of fitness is little changed and unconstrained proliferation will resume once resistance evolves. Robust population control is possible if resistance to therapy requires a substantial and costly phenotypic adaptation that also significantly reduces the organism's fitness in its original niche: an evolutionary double bind. [Cancer Res 2009;69(19):7499–502]
Exposure to second-hand smoke and reproductive outcomes depending on maternal asthma
Authors: Jordi Sunyer, Raquel Garcia-Esteban, Ane Miren Castilla, Juan José Aurrekoetxea, Carmen Iñiguez, Adonina Tardón, Mercedes Espada, Aitana Lertxundi, Leda Chatzi, Marisa Rebagliato, Manolis Kogevinas
Journal: European Respiratory Journal (2012)

Tobacco consumption and exposure to second-hand smoke (SHS) are associated with reduced birth weight. One issue that has not been clarified previously is that of the potential higher risk of this outcome in mothers with asthma. We assessed the role of prenatal maternal tobacco use and SHS on reproductive outcomes and assessed the interaction with maternal history of asthma. Data was collected from the INMA study, a maternal birth cohort selected from the general population established in Spain in 2002. We measured cotinine at the 32nd week of pregnancy in 2,219 females. Diagnosed maternal asthma was self-reported during pregnancy. 35% of mothers reported not being exposed to smoking or SHS during pregnancy. Active smoking ( i.e. self-reported or cotinine &gt;50 ng·mL −1 ) was related to a 134 g decrease in birth weight and a relative risk of 1.8 for small for gestational age and fetal growth restriction. These results were not modified by maternal asthma. Maternal asthma had a similar frequency in all exposure groups. Non SHS-exposed females had the lowest prevalence of asthma. SHS ( i.e. cotinine 20–50 ng·mL −1 ) decreased birth weight by 32 g among those without maternal asthma, but these differences were not statistically significant (95% CI -88.76–24.76). Maternal asthma did not promote these effects. Maternal history of asthma did not modify the effects of smoking on reproductive outcomes in a cohort sampled from the general population.
Human four-and-a-half LIM family members suppress tumor cell growth through a TGF-β–like signaling pathway
Authors: Lihua Ding, Zhaoyun Wang, Jinghua Yan, Xiao Yang, Aijun Liu, Weiyi Qiu, Jianhua Zhu, Juqiang Han, Hao Zhang, Jing Lin, Long Cheng, Xi Qin, Chang Niu, Bin Yuan, Xiaohui Wang, Cui Zhu, Yan Zhou, Jiezhi Li, Haifeng Song, Cuifen Huang, Qinong Ye
Journal: Journal of Clinical Investigation (2009)

The four-and-a-half LIM (FHL) proteins belong to a family of LIM-only proteins that regulate cell proliferation, differentiation, and apoptosis. The exact functions of each FHL protein in cancer development and progression remain unknown. Here we report that FHL1, FHL2, and FHL3 physically and functionally interact with Smad2, Smad3, and Smad4, important regulators of cancer development and progression, in a TGF-β–independent manner. Casein kinase 1δ, but not the TGF-β receptor, was required for the FHL-mediated TGF-β–like responses, including increased phosphorylation of Smad2/3, interaction of Smad2/3 and Smad4, nuclear accumulation of Smad proteins, activation of the tumor suppressor gene p21, and repression of the oncogene c-myc. FHL1–3 inhibited anchorage-dependent and -independent growth of a human hepatoma cell line in vitro and tumor formation in nude mice. Further analysis of clinical samples revealed that FHL proteins are often downregulated in hepatocellular carcinomas and that this correlates with decreased TGF-β–like responses. By establishing a link between FHL proteins and Smad proteins, this study identifies what we believe to be a novel TGF-β–like signaling pathway and indicates that FHL proteins may be useful molecular targets for cancer therapy.
Wnt signalling in smooth muscle cells and its role in cardiovascular disorders
Authors: C. Mill, S. J. George
Journal: Cardiovascular Research (2012)

Vascular smooth muscle cells (SMCs) are the major cell type within blood vessels. SMCs exhibit low rates of proliferation, migration, and apoptosis in normal blood vessels. However, increased SMC proliferation, migration, and apoptosis rates radically alter the composition and structure of the blood vessel wall and contribute to cardiovascular diseases, such as atherosclerosis, and restenosis that occur after coronary artery vein grafting and stent implantation. Consequently, therapies that modulate SMC proliferation, migration, and apoptosis may be useful for treating cardiovascular diseases. The family of Wnt proteins, which were first identified in the wingless drosophila, has a well-established role in embryogenesis and development. It is now emerging that Wnt proteins also regulate SMC proliferation, migration, and survival. In this review article, we discuss recently emerging research that has revealed that Wnt proteins are important regulators of SMC behaviour via activation of β-catenin-dependent and β-catenin-independent Wnt signalling pathways.
Recombinant ob protein reduces feeding and body weight in the ob/ob mouse.
Authors: D S Weigle, T R Bukowski, D C Foster, S Holderman, J M Kramer, G Lasser, C E Lofton-Day, D E Prunkard, C Raymond, J L Kuijper
Journal: Journal of Clinical Investigation (1995)

To determine whether the product of the recently cloned ob gene functions as an adipose-related satiety factor, recombinant murine ob protein was administered intraperitoneally to ob/ob mice. Monomeric ob protein given as single morning injections to groups of three animals at seven doses ranging from 5 to 100 micrograms reduced 24-h chow consumption in a dose-dependent manner from values of 81 +/- 6.8% of control (10-micrograms dose, P = 0.04) to 29 +/- 7.7% of control (100-micrograms dose, P < 0.0001). Daily injections of 80 micrograms of ob protein into six ob/ob mice for 2 wk led to an 11 +/- 1.6% decrease in body weight (P = 0.0009) and suppressed feeding to 26 +/- 4.9% of baseline (P < 0.0001), with significant reduction of serum insulin and glucose levels. The effect of recombinant ob protein on feeding was not augmented by cofactors secreted by adipose tissue, nor did exposure of adipose tissue to ob protein affect intracellular ob mRNA levels. Posttranslational modification of ob protein was not required for activity; however, addition of a hexahistidine tag to the amino terminus of the mature ob protein resulted in prolonged suppression of feeding after injection into ob/ob mice. These results demonstrate a direct effect of the ob protein to suppress feeding in the ob/ob mouse and suggest that this molecule plays a critical role in regulating total body fat content.
Diagnosis of Hookworm Disease
Authors: L. McIntyre
Journal: JAMA (1982)

<h3>To the Editor.—</h3> The article by De la Riva et al (1981;246:68) regarding a 19-year-old man with acute, massive, intestinal bleeding caused by hookworm leaves three areas of contention. Though the surgeons reported "large numbers" of hookworm in the patient's jejunum and the observers described "many hookworm excreted" in the feces after treatment, a diagnosis of heavy worm burden should not be made without fecal egg counts. In addition, no mention of the patient's coagulation status nor of aspirin or alcohol intake was made in the article as these factors can facilitate major blood loss with a minimal underlying pathological condition. The observation that the patient returned two months after his gastrointestinal bleeding with hepatosplenomegaly, an elevated SGOT level, lymphadenopathy, and mild eosinophilia with hookworm seen on stool examination in no way implicates hookworm as the cause of the patient's disease. A 19-year-old man with this syndrome would be more
Admitting lung cancer patients to intensive care for organ dysfunction: a complex decision process
Authors: Anne-Pascale Meert, Thierry Berghmans, Jean-Paul Sculier
Journal: European Respiratory Journal (2015)

Physicians in charge of patients with lung cancer not only face the cancer itself but also major comorbidities due to tobacco exposure. In addition to complications of lung cancer and anticancer treatments, chronic obstructive pulmonary disease exacerbations and cardiovascular disease, for example, are situations that can potentially lead patients with lung cancer to emergency wards and, finally, intensive care units (ICUs). Lung cancer represents up to 15–20% of ICU admissions in cancer patients. The reasons for ICU admission are primarily respiratory problems, with pneumonia being the leading cause, and sepsis and shock as the second and third aetiologies. With adequate selection, intensive care and mechanical ventilation should not be considered futile in lung cancer <http://ow.ly/E3lB1>