tbuckley/cabot-search huggingface dataset:
Lichen planus pemphigoides: an immuno-electron microscopic study
Authors: C. PROST, F. TESSERAND, L. LAROCHE, A. DALLOT, O. VEROLA, P. MOREL, L. DUBERTRET
Journal: British Journal of Dermatology (1985)

Journal Article Lichen planus pemphigoides: an immuno‐electron microscopic study Get access C. PROST, C. PROST Department of Dermatology, Höpital Henri Mondor, Creteil, France C.Prost, Department of Dermatology, Höpital Henri Mondor, 94010 Creteil, France. Search for other works by this author on: Oxford Academic Google Scholar F. TESSERAND, F. TESSERAND Department of Dermatology, Höpital St. Louis, Paris, France Search for other works by this author on: Oxford Academic Google Scholar L. LAROCHE, L. LAROCHE Department of Dermatology, Höpital St. Louis, Paris, France Search for other works by this author on: Oxford Academic Google Scholar A. DALLOT, A. DALLOT Department of Dermatology, Höpital St. Louis, Paris, France Search for other works by this author on: Oxford Academic Google Scholar O. VEROLA, O. VEROLA Department of Pathology, Höpital St. Louis, Paris, France Search for other works by this author on: Oxford Academic Google Scholar P. MOREL, P. MOREL Department of Dermatology, Höpital St. Louis, Paris, France Search for other works by this author on: Oxford Academic Google Scholar L. DUBERTRET L. DUBERTRET Department of Dermatology, Höpital Henri Mondor, Creteil, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue 1, 1 July 1985, Pages 31–36, https://doi.org/10.1111/j.1365-2133.1985.tb02041.x Published: 01 July 1985 Article history Accepted: 27 November 1984 Published: 01 July 1985
Guidelines for Guidelines: Measuring Trustworthiness
Authors: David F. Ransohoff, Harold C. Sox
Journal: Journal of Clinical Oncology (2013)

AstheUnitedStatesfinallybecomesseriousaboutcontrolling the costs of health care, the public needs practice standards that fairly reflect the best evidence about what works best for which patients. Clinical practice guidelines (CPGs) should fill this need. They are important not only because they affect outcomes for individual patients but also because they increasingly shape a large proportion of patient care—that which is straightforward and subject to standardization—through standards of practice, practice quality measures, and insurance coverage decisions. Althoughpracticerecommendationsshouldfaithfullyreflectthe best evidence, we lack a proven measure of quality or trustworthiness to help us choose between guidelines with conflicting recommendations. The National Guideline Clearinghouse currently lists prostate cancerscreeningguidelinesfromeightUnitedStates‐basedorganizations. 1 None are exactly alike, and the recommendations range from “never screen” to “screen everyone.” How can we tell which clinical practice guideline to trust? Judging the quality of CPGs is a terra incognita that we are just starting to explore. One study of guideline quality,publishedinthearticlethataccompaniesthiseditorial, 2 builds on recently published standards for trustworthy guidelines by the Institute of Medicine (IOM). 3,4 Its findings illustrate the challenges facing our profession as we explore this new area. TheefforttocreateatrustworthyprocessfordevelopingCPGs
Autologous stem cell transplantation improves microcirculation in systemic sclerosis
Authors: I Miniati, S Guiducci, M L Conforti, V Rogai, G Fiori, M Cinelli, R Saccardi, S Guidi, A Bosi, A Tyndall, M Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2008)

Background: In systemic sclerosis (SSc) reduced capillary density decreases blood flow and leads to tissue ischaemia and fingertip ulcers. Nail fold videocapillaroscopy (NVC) is a diagnostic and follow-up parameter useful to evaluate the severity, activity and the stage of SSc microvascular damage. Autologous haemopoietic stem cell transplantation (HSCT) is a new treatment for patients with severe diffuse cutaneous systemic sclerosis (dcSSc) refractory to conventional therapies. We aimed to evaluate the improvement of microvasculature after HSCT using NVC. Methods: A total of 16 patients with severe dcSSc with a “late” videocapillaroscopy pattern underwent an immunesuppressive treatment: 6 were treated with HSCT and 10 with monthly pulse cyclophosphamide (CYC) 1 g for 6 months and then orally with 50 mg/day for further 6 months. NVC was performed before and after 3 months from the beginning of each treatment and then repeated every 3 months. Results: In all patients, before HSCT NVC showed large avascular areas and ramified capillaries and vascular architectural disorganisation (“late” pattern). At 3 months after HSCT, the NVC pattern changed from “late” into “active”, showing frequent giant capillaries (&gt;6/mm) and haemorrhages, absence of avascular areas and angiogenesis phenomena; 1 year after HSCT, microvascular abnormalities were still in the “active” pattern. In patients treated with CYC, no NVC modifications were observed during 24 months of follow-up and the pattern always remained “late”. Conclusions: These results indicate that HSCT with a high dose CYC regimen may foster vascular remodelling, while CYC at lower doses and with a chronic regimen does not influence the microvasculature.
“The Street Will Drive You Crazy”: Why Homeless Psychotic Women in the Institutional Circuit in the United States Often Say No to Offers of Help
Authors: Tanya Marie Luhrmann
Journal: American Journal of Psychiatry (2007)

Many people who struggle with psychotic disorder often refuse offers of help, including housing, extended by mental health services. This article uses the ethnographic method to examine the reasons for such refusal among women who are homeless and psychiatrically ill in the institutional circuit in an urban area of Chicago. It concludes that such refusals arise not only from a lack of insight but also from the local culture's ascription of meaning to being "crazy." These data suggest that offers of help-specifically, diagnosis-dependent housing-to those on the street may be more successful when explicit psychiatric diagnosis is downplayed.
A role for proteinase-activated receptor–1 in inflammatory bowel diseases
Authors: Nathalie Vergnolle, Laurie Cellars, Andrea Mencarelli, Giovanni Rizzo, Sunita Swaminathan, Paul Beck, Martin Steinhoff, Patricia Andrade-Gordon, Nigel W. Bunnett, Morley D. Hollenberg, John L. Wallace, Giuseppe Cirino, Stefano Fiorucci
Journal: Journal of Clinical Investigation (2004)

Proteinase-activated receptor-1 (PAR1), a G protein-coupled receptor activated by thrombin, is highly expressed in different cell types of the gastrointestinal tract. The activity of thrombin and of other proteinases is significantly increased in the colon of inflammatory bowel disease (IBD) patients. Since PAR1 activation in tissues other than the gut provoked inflammation, we hypothesized that PAR1 activation in the colon is involved in the pathogenesis of IBD. Here, we demonstrate that PAR1 is overexpressed in the colon of IBD patients. In mice, intracolonic administration of PAR1 agonists led to an inflammatory reaction characterized by edema and granulocyte infiltration. This PAR1 activation-induced inflammation was dependent on B and T lymphocytes. Moreover, PAR1 activation exacerbated and prolonged inflammation in a mouse model of IBD induced by the intracolonic administration of trinitrobenzene sulfonic acid (TNBS), while PAR1 antagonism significantly decreased the mortality and severity of colonic inflammation induced by TNBS and dextran sodium sulfate. In these 2 models, colitis development was strongly attenuated by PAR1 deficiency. Taken together, these results imply an important role for PAR1 in the pathogenesis of experimental colitis, supporting the notion that PAR1 inhibition may be beneficial in the context of IBD and possibly in other chronic intestinal inflammatory disorders.
Punctate LC3B Expression Is a Common Feature of Solid Tumors and Associated with Proliferation, Metastasis, and Poor Outcome
Authors: Rossitza Lazova, Robert L. Camp, Vincent Klump, Summar F. Siddiqui, Ravi K. Amaravadi, John M. Pawelek
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Measurement of autophagy in cancer and correlation with histopathologic grading or clinical outcomes has been limited. Accordingly, we investigated LC3B as an autophagosome marker by analyzing nearly 1,400 tumors from 20 types of cancer, focusing on correlations with clinical outcomes in melanoma and breast cancer. Experimental Design: Staining protocols were developed for automated quantitative analysis (AQUA) using antibodies versus LC3 isoform B (LC3B) and Ki-67. Clinically annotated breast and melanoma tissue microarrays (TMA) and a multitumor array were used. An AQUA program was developed to quantitate LC3B distribution in punctate and diffuse compartments of the cell. Results: LC3B staining was moderate to high in the large majority of tumors. The percentage of area occupied by punctate LC3B was elevated by 3- to 5-fold at high LC3B intensities. In breast cancer and melanoma TMAs, LC3B and Ki-67 showed strong correlations (P &amp;lt; 0.0001), and in multitumor TMAs, mitotic figures were most often seen in tumors with the highest LC3B expression (P &amp;lt; 0.002). In breast cancer, LC3B expression was elevated in node-positive versus node-negative primaries and associated with increased nuclear grade and shortened survival. In a melanoma TMA with no survival data, LC3B levels were highest in nodal, visceral, and cutaneous metastases. Conclusions: The results reveal a common expression of LC3B in malignancy and support emerging evidence that autophagy plays a significant role in cancer progression. High LC3B was associated proliferation, invasion and metastasis, high nuclear grade, and worse outcome. Thus, autophagy presents a key target of therapeutic vulnerability in solid tumors. Clin Cancer Res; 18(2); 370–9. ©2011 AACR.
Genealogy of families of SINEs in cetaceans and artiodactyls: the presence of a huge superfamily of tRNA(Glu)-derived families of SINEs
Authors: M. Shimamura, H. Abe, M. Nikaido, K. Ohshima, N. Okada
Journal: Molecular Biology and Evolution (1999)

Several novel (sub)families of SINEs were isolated from the genomes of cetaceans and artiodactyls, and their sequences were determined. From comparisons of diagnostic nucleotides among the short interspersed repetitive elements (SINEs) in these (sub)families, we were able to draw the following conclusions. (1) After the divergence of the suborder Tylopoda (camels), the CHRS family of SINEs was newly created from tRNA(Glu) in a common ancestor of the lineages of the Suina (pigs and peccaries), Ruminantia (cows and deer), and Cetacea (whales and dolphins). (2) After divergence of the Suina lineage, the CHR-1 SINE and the CHR-2 SINE were generated successively in a common ancestor of ruminants, hippopotamuses, and cetaceans. (3) In the Ruminantia lineage, the Bov-tA SINE was generated by recombination between the CHR-2 SINE and Bov-A. (4) In the Suina lineage, the CHRS-S SINE was generated from the CHRS SINE. (5) In this latter lineage, the PRE-1 family of SINEs was created by insertion of part of the gene for tRNA(Arg) into the 5' region of the CHRS-S family. The distribution of a particular family of SINEs among species of artiodactyls and cetaceans confirmed the most recent conclusion for paraphyly of the order Artiodactyla. The present study also revealed that a newly created tRNA(Glu)-derived family of SINEs was subjected both to recombination with different units and to duplication of an internal sequence within a SINE unit to generate, during evolution, a huge superfamily of tRNA(Glu)-related families of SINEs that are now found in the genomes of artiodactyls and cetaceans.
Glycosylation of G-protein-coupled receptors for hormones central to normal reproductive functioning: its occurrence and role
Authors: M Wheatley
Journal: Human Reproduction Update (1999)

Many hormones that are central to normal reproductive functioning mediate their physiological effects by activating a receptor which belongs to the large family of G-protein-coupled receptors (GPCR). Members of this family of receptor proteins are usually glycosylated on extracellular domains. In recent years the role of this glycosylation in cells surface expression/protein folding, ligand recognition and receptor-effector coupling has been investigated. This review summarises current knowledge of the role of glycosylation in the functioning of the receptors for gonadotrophin-releasing hormone (GnRH), luteinizing hormone/human chorionic gonadotrophin (LH/HCG), follicle stimulating hormone (FSH), oxytocin (OT) and vasopressin (AVP).
Role of Renocortical Cyclooxygenase-2 for Renal Vascular Resistance and Macula Densa Control of Renin Secretion
Authors: HAYO CASTROP, FRANK SCHWEDA, KARL SCHUMACHER, KONRAD WOLF, ARMIN KURTZ
Journal: Journal of the American Society of Nephrology (2001)

This study aimed to assess the role of cyclooxygenase-2 (COX-2)-derived prostanoids for the macula densa control of renal afferent arteriolar resistance and for renin secretion. For this purpose, studied were the effects of blocking macula densa salt transport by the loop diuretic bumetanide (100 microM) on renal perfusate flow and on renin secretion in isolated perfused rats, in which renocortical COX-2 expression was prestimulated in vivo by treatment with the angiotensin-converting enzyme inhibitor ramipril, with low-salt diet, or with a combination of both. These maneuvers stimulated COX-2 expression in an order of ramipril + low salt>> low salt > ramipril > controls. Flow rates through isolated kidneys at a constant pressure of 100 mmHg were dependent on the pretreatment regimen, in the way that they went in parallel with COX-2 expression. The COX-2 inhibitor NS-398 (10 microM) lowered flow rates depending on the COX-2 expression level and was most pronounced therefore after pretreatment with low salt + ramipril. NS-398 did not change the increase of flow in response to bumetanide but attenuated the stimulation of renin secretion in response to bumetanide in a manner depending on the expression level of COX-2. These findings suggest that in states of increased renocortical expression of COX-2, overall renal vascular resistance and the macula densa control of renin secretion become dependent on COX-2-derived prostanoids.
Remnant Lipoprotein Levels in Fasting Serum Predict Coronary Events in Patients With Coronary Artery Disease
Authors: Kiyotaka Kugiyama, Hideki Doi, Keiji Takazoe, Hiroaki Kawano, Hirofumi Soejima, Yuji Mizuno, Ryusuke Tsunoda, Tomohiro Sakamoto, Takamitsu Nakano, Katsuyuki Nakajima, Hisao Ogawa, Seigo Sugiyama, Michihiro Yoshimura, Hirofumi Yasue
Journal: Circulation (1999)

Remnant lipoproteins are atherogenic, but assays of remnants have not been available in routine clinical laboratories because of the lack of practical and validated methods. A simple and reliable method for such an assay, using an immunochemical approach, has recently been developed. This study prospectively examined whether remnant lipoprotein levels in fasting serum, measured by our method, may have prognostic value in patients with coronary artery disease (CAD).Remnant lipoprotein levels in fasting serum were measured in 135 patients with CAD by an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. Patients were followed up for </=36 months until occurrence of 1 of the following clinical coronary events: recurrent or refractory angina pectoris requiring coronary revascularization, nonfatal myocardial infarction, or cardiac death. Kaplan-Meier analysis demonstrated a significantly higher probability of developing coronary events in patients with the highest tertile of remnant levels (>5.1 mg cholesterol/dL; 75th percentile of distribution of remnant levels) than in those with the lowest tertile of remnant levels (</=3.3 mg cholesterol/dL; 50th percentile of the distribution). Higher levels of remnants were a significant and independent predictor of developing coronary events in multivariate Cox hazard analysis including the following covariates: extent of coronary artery stenosis, age, sex, smoking, hypertension, diabetes mellitus, hypercholesterolemia, low HDL cholesterol, and hypertriglyceridemia.Higher levels of remnant lipoproteins in fasting serum predict future coronary events in patients with CAD independently of other risk factors. Thus, measurement of fasting remnant levels, assessed by the current immunoseparation method, may be helpful in assessment of CAD risk.
RNA editing in <i>RHOQ</i> promotes invasion potential in colorectal cancer
Authors: Sae-Won Han, Hwang-Phill Kim, Jong-Yeon Shin, Eun-Goo Jeong, Won-Chul Lee, Keon Young Kim, Sang Youn Park, Dae-Won Lee, Jae-Kyung Won, Seung-Yong Jeong, Kyu Joo Park, Jae-Gahb Park, Gyeong Hoon Kang, Jeong-Sun Seo, Jong-Il Kim, Tae-You Kim
Journal: The Journal of Experimental Medicine (2014)

RNA editing can increase RNA sequence variation without altering the DNA sequence. By comparing whole-genome and transcriptome sequence data of a rectal cancer, we found novel tumor-associated increase of RNA editing in ras homologue family member Q (RHOQ) transcripts. The adenosine-to-inosine (A-to-I) editing results in substitution of asparagine with serine at residue 136. We observed a higher level of the RHOQ RNA editing in tumor compared with normal tissue in colorectal cancer (CRC). The degree of RNA editing was associated with RhoQ protein activity in CRC cancer cell lines. RhoQ N136S amino acid substitution increased RhoQ activity, actin cytoskeletal reorganization, and invasion potential. KRAS mutation further increased the invasion potential of RhoQ N136S in vitro. Among CRC patients, recurrence was more frequently observed in patients with tumors having edited RHOQ transcripts and mutations in the KRAS gene. In summary, we show that RNA editing is another mechanism of sequence alteration that contributes to CRC progression.
DNA Mismatch Repair Initiates 6-Thioguanine–Induced Autophagy through p53 Activation in Human Tumor Cells
Authors: Xuehuo Zeng, Tao Yan, Jane E. Schupp, Yuji Seo, Timothy J. Kinsella
Journal: Clinical Cancer Research (2007)

We investigate the roles of DNA mismatch repair (MMR) and p53 in mediating the induction of autophagy in human tumor cells after exposure to 6-thioguanine (6-TG), a chemotherapy drug recognized by MMR. We also examine how activation of autophagy affects apoptosis (type I cell death) after MMR processing of 6-TG.Using isogenic pairs of MLH1(-)/MLH1(+) human colorectal cancer cells (HCT116) and MSH2(-)/MSH2(+) human endometrial cancer cells (HEC59), we initially measure activation of autophagy for up to 3 days after 6-TG treatment using LC3, a specific marker of autophagy. We then assess the role of p53 in autophagic signaling of 6-TG MMR processing using both pifithrin-alpha cotreatment to chemically inhibit p53 transcription and small hairpin RNA inhibition of p53 expression. Finally, we use Atg5 small hairpin RNA inhibition of autophagy to assess the effect on apoptosis after MMR processing of 6-TG.We find that MMR is required for mediating autophagy in response to 6-TG treatment in these human tumor cells. We also show that p53 plays an essential role in signaling from MMR to the autophagic pathway. Finally, our results indicate that 6-TG-induced autophagy inhibits apoptosis after MMR processing of 6-TG.These data suggest a novel function of MMR in mediating autophagy after a chemical (6-TG) DNA mismatch damage through p53 activation. The resulting autophagy inhibits apoptosis after MMR processing of 6-TG.
Inhibition of Insulin-Like Growth Factor 1 Receptor by CP-751,871 Radiosensitizes Non–Small Cell Lung Cancer Cells
Authors: Tsutomu Iwasa, Isamu Okamoto, Minoru Suzuki, Erina Hatashita, Yuki Yamada, Masahiro Fukuoka, Koji Ono, Kazuhiko Nakagawa
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Therapeutic strategies that target the insulin-like growth factor I receptor (IGF-1R) hold promise for a wide variety of cancers. We have now investigated the effect of CP-751,871, a fully human monoclonal antibody specific for IGF-IR, on the sensitivity of human non–small cell lung cancer (NSCLC) cell lines to radiation. Experimental Design: The radiosensitizing effect of CP-751,871 was evaluated on the basis of cell death, clonogenic survival, and progression of tumor xenografts. Radiation-induced damage was evaluated by immunofluorescence analysis of the histone γ-H2AX and Rad51. Results: A clonogenic survival assay revealed that CP-751,871 increased the sensitivity of NSCLC cells to radiation in vitro. CP-751,871 inhibited radiation-induced IGF-IR signaling, and potentiated the radiation-induced increases both in the number of apoptotic cells and in the activity of caspase-3. Immunofluorescence analysis of the histone γ-H2AX and Rad51 also showed that CP-751,871 inhibited the repair of radiation-induced DNA double-strand breaks. Finally, combination therapy with CP-751,871 and radiation delayed the growth of NSCLC tumor xenografts in nude mice to a greater extent than did either treatment modality alone. Conclusions: These results show that CP-751,871 sensitizes NSCLC cells to radiation both in vitro and in vivo, and that this effect of CP-751,871 is likely attributable to the inhibition of DNA repair and enhancement of apoptosis that result from attenuation of IGF-IR signaling. Combined treatment with CP-751,871 and radiation thus warrants further investigation in clinical trials as a potential anticancer strategy. (Clin Cancer Res 2009;15(16):5117–25)
Behavioral Disinhibition Induced by Tryptophan Depletion in Nonalcoholic Young Men With Multigenerational Family Histories of Paternal Alcoholism
Authors: David G. LeMarquand, Chawki Benkelfat, Robert O. Pihl, Roberta M. Palmour, Simon N. Young
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: A deficit in serotonergic neurotransmission has been linked to impulsive behavior, as well as to disorders characterized by disinhibition. The present study tested the hypothesis that young men at high risk for alcoholism demonstrate greater behavioral disinhibition after acute dietary depletion of tryptophan, the amino acid precursor of serotonin. METHOD: A double-blind, placebo-comparison, between-subjects study design was used. Nonalcoholic young men with a multigenerational paternal family history of alcoholism (N=13) or with no family history of alcoholism (N=15) in two previous generations were administered mixtures of tryptophan-deficient amino acid to achieve plasma tryptophan depletion. Comparison subjects with a multigenerational paternal family history of alcoholism (N=11) and comparison subjects with no family history of alcoholism (N=18) were given a balanced mixture. Five hours after this, all were tested on a modified Taylor task and a go/no-go task measuring aggressive response and disinhibition, respectively. RESULTS: Plasma tryptophan levels were reduced by 89% in both groups. Tryptophan depletion had no effect on aggressive response. In contrast, tryptophan-depleted individuals with a family history of alcoholism made more commission errors (responses to stimuli associated with punishment or loss of reward) than did tryptophan-depleted individuals with no family history of alcoholism and those receiving the balanced (comparison) mixture of amino acid in either group. CONCLUSIONS: Low serotonin levels may be implicated in the high disinhibition or impulsivity observed in some individuals with a genetic vulnerability to alcohol abuse or dependence.
The Application of Artificial Intelligence to Microarray Data: Identification of a Novel Gene Signature to Identify Bladder Cancer Progression
Authors: James W.F. Catto, Maysam F. Abbod, Peter J. Wild, Derek A. Linkens, Christian Pilarsky, Ishtiaq Rehman, Derek J. Rosario, Stefan Denzinger, Maximilian Burger, Robert Stoehr, Ruth Knuechel, Arndt Hartmann, Freddie C. Hamdy
Journal: European Urology (2009)