tbuckley/cabot-search huggingface dataset:
My journey from anti to pro assisted dying
Authors: S. H. Ahmedzai
Journal: BMJ (2012)

I support the move to make doctors’ professional organisations neutral about assisted dying.1 2 As a consultant in hospice and hospital palliative medicine for 27 years, I have, however, been fervently against changing the law in this respect. I remain sceptical about euthanasia (the deliberate ending of a life by an act performed by another person). But in recent years I have radically moved my position on assisted suicide—when a competent …
Tasisulam Sodium (LY573636 Sodium) as Third-Line Treatment in Patients With Unresectable, Metastatic Non–Small-Cell Lung Cancer: A Phase-II Study
Authors: Giorgio V. Scagliotti, Robert Ilaria, Silvia Novello, J. von Pawel, Juergen R. Fischer, Sabine Ermisch, Dinesh P. de Alwis, Joan Andrews, Martin Reck, Lucio Crino, Corinna Eschbach, Christian Manegold
Journal: Journal of Thoracic Oncology (2012)
Dysregulation of global microRNA expression in splenic marginal zone lymphoma and influence of chronic hepatitis C virus infection
Authors: J Peveling-Oberhag, G Crisman, A Schmidt, C Döring, M Lucioni, L Arcaini, S Rattotti, S Hartmann, A Piiper, W-P Hofmann, M Paulli, R Küppers, S Zeuzem, M-L Hansmann
Journal: Leukemia (2012)
Demonstration of Increased Bone Metabolism in Melorheostosis by Multiphase Bone Scanning
Authors: JOHN MAHONEY, DWIGHT M. ACHONG
Journal: Clinical Nuclear Medicine (1991)

The multiphase bone scan features of melorheostosis are presented. Early increased tracer delivery demonstrated by blood pool imaging supports the concept of ongoing accelerated bony metabolism as a cause of tracer uptake within the osteosclerotic lesions of melorheostosis. There is excellent correlation between the scintigraphic and radiographic distribution of these lesions.
Glycosylated Hemoglobin Predicts the Incidence and Progression of Diabetic Retinopathy
Authors: Ronald Klein
Journal: JAMA (1988)

The relationship between hyperglycemia, measured by glycosylated hemoglobin at the initial examination, and the four-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Younger- (n = 891) and older-onset (n = 987) persons participating in baseline and follow-up examinations were included. Glycosylated hemoglobin was measured by microcolumn. Retinopathy was determined from stereoscopic fundus photographs. In the younger-onset group, comparing the highest with the lowest quartile of glycosylated hemoglobin, the relative risk for developing any diabetic retinopathy was 1.9; for proliferative retinopathy, 21.8; and for progression, 4.0. Among older-onset persons taking insulin, the corresponding relative risks were 1.9, 4.0, and 2.1. Among older-onset persons not taking insulin, relative risks were 4.0 for any retinopathy and 6.2 for progression. A positive relationship between incidence and progression of retinopathy and glycosylated hemoglobin remained after controlling for duration of diabetes, age, sex, and baseline retinopathy. These data suggest a strong and consistent relationship between hyperglycemia and incidence and progression of retinopathy.
Non-fatal overdosing is related to polydrug use in Glasgow
Authors: A. Taylor, M. Frischer, D. Goldberg
Journal: BMJ (1996)

Case 1-A 76 year old woman received the treatment for multifocal motor neuropathy.One week after treatment she developed a widespread erythematous, exfoliating rash, which was diagnosed after skin biopsy as being severe erythroderma.This required three months of intensive and predominantly inpatient dermatological care.The neuropathy initially responded to the intravenous immunoglobulin but then relapsed.After extensive patch testing with various brands of intravenous immunoglobulin, none of which resulted in a positive reaction, she was given a further course covered by oral steroids, but within six hours of the first dose the rash returned.Case 2-A 66 year old man with inclusion body myositis developed itchy skin eruptions six days after receiving the Scottish preparation of intravenous immunoglobulin.Skin biopsy suggested an allergic aetiology.He had a further six courses of the same preparation at monthly intervals with oral steroid cover.No further complications developed.Case 3-A 48 year old man with multifocal motor neuropathy developed a widespread eczematous rash 10 days after treatment with intravenous immunoglobulin.He was admitted to hospital after failure of outpatient treatment.Skin biopsy showed perivascular inflammation, hyperkeratosis, and parakeratosis without evidence of vasculitis.Case 4-A 55 year old man received intravenous immunoglobulin for multifocal motor neuropathy.One week after treatment he developed widespread itchy, scaly eruptions, mainly on the arms and legs, which persisted for four weeks.Recovery was spontaneous and uneventful.Serious side effects of intravenous immuno- globulin are rare.There are only a few reports of skin reactions in the literature2; although rarely life threatening, they may cause considerable distress (as they did in cases 1 and 3).A patient has been successfully treated with intravenous immuno- globulin and steroid cover after developing eczema,3 and the combination of intravenous immunoglobulin and steroid has been evaluated recently.4This may well be optimal treatment, if only because the side effects of the immunoglobu- lin are lessened, but our experience is that the skin condition may recur despite such treatment.
Mitogen-Activated Protein Kinase Phosphatase 2: A Novel Transcription Target of p53 in Apoptosis
Authors: Wen Hong Shen, Jianli Wang, Jingjing Wu, Victor B. Zhurkin, Yuxin Yin
Journal: Cancer Research (2006)

Abstract The p53 tumor suppressor plays critical roles in diverse cellular responses such as cell cycle arrest, senescence, and apoptosis through transcriptional control of its target genes. Identification and characterization of new p53 target genes will advance our understanding of how p53 exerts its multiple regulatory functions. In this article, we show that mitogen-activated protein kinase phosphatase 2 (MKP2) is a novel transcription target of p53 in mediating apoptosis. Moreover, we identify a 10-bp perfect palindrome motif (CTGGCGCCAG) in the MKP2 promoter as a new binding site for p53 to activate the MKP2 gene. This GC-rich palindrome is completely different from the consensus p53 binding sequence. Induction of MKP2 is highly responsive to oxidative stress in a p53-dependent manner. Interestingly, the p53-dependent induction of MKP2 is prominent only in the cellular response to stimuli leading to apoptosis but not to cell cycle arrest. In response to oxidative stress, MKP2 is not only required for p53-mediated apoptosis, but ectopic MKP2 expression can also enhance apoptotic responses even independent of p53. These data suggest that p53 regulates distinct genes via different binding mechanisms and that MKP2 is an essential target of p53 in signaling apoptosis. (Cancer Res 2006; 66(12): 6033-9)
Pamidronate induced anti-proliferative, apoptotic, and anti-migratory effects in hepatocellular carcinoma
Authors: Akira Wada, Koji Fukui, Yoshiyuki Sawai, Kazuho Imanaka, Shinichi Kiso, Shinji Tamura, Iichiro Shimomura, Norio Hayashi
Journal: Journal of Hepatology (2005)
P223Facing up the problem of no need for routine laboratory monitoring of new oral anticoagulants (direct thrombin inhibitors, direct factor Xa inhibitors)
Authors: D Kuleshova, AG Obrezan
Journal: Cardiovascular Research (2014)

Purpose: To assess the problem of no need for routine coagulation laboratory monitoring of direct thrombin inhibitors and direct factor Xa inhibitors. Methods: 52 patients with nonvalvular atrial fibrillation, coronary artery disease and at least one CHA2DS2VASc risk factor were enrolled. Mean CHA2DS2VASc score 4,6, mean HAS-BLED score 2. Exclusion criteria: eGFR < 30 ml/min. 40 patients (18 females and 22 males), receiving dabigatran etexilate bid (75, 110 or 150mg). 12 patients (6 females and 6 males) receiving 15 or 20mg q.d. Results: Taking into account prescribing information, the laboratory monitoring was not obtained. Sporadic coagulation measurements showed thrombin time significant (at least two-fold) extension at the end of the first week of therapy with dabigatran and in some cases had reached 240 seconds. After a month of therapy some patients had thrombin time at the upper limit of normal. However in several examples it remained about 2-4 fold increased in a dose-dependent manner (dabigatran 150 mg bid). Furthermore, after the first week of therapy the aPTT was prolonged by 1.5-2.2 times in comparison to the initial value and reached the upper limits of normal by the end of the first month. Blood test revealed 14-32% reduction in platelet count compared to baseline (up to 52% in one patient). These phenomena appeared to be dose-independent. Conclusions: At present, due to the lack of recommendations the anticoagulation monitoring is not carried out. In most cases, doctors had no information on real changes in blood coagulation. Further studies are necessary to find the affordable algorithm for the monitoring of long-term anticoagulation therapy. Interaction with other pharmacological agents (especially with anti-arrhythmic drugs) should be specified.
Angiotensin II–Mediated Adaptive and Maladaptive Remodeling of Cardiomyocyte Excitation–Contraction Coupling
Authors: Konstantin Gusev, Andrea A. Domenighetti, Lea M.D. Delbridge, Thierry Pedrazzini, Ernst Niggli, Marcel Egger
Journal: Circulation Research (2009)

Cardiac hypertrophy is associated with alterations in cardiomyocyte excitation-contraction coupling (ECC) and Ca(2+) handling. Chronic elevation of plasma angiotensin II (Ang II) is a major determinant in the pathogenesis of cardiac hypertrophy and congestive heart failure. However, the molecular mechanisms by which the direct actions of Ang II on cardiomyocytes contribute to ECC remodeling are not precisely known. This question was addressed using cardiac myocytes isolated from transgenic (TG1306/1R [TG]) mice exhibiting cardiac specific overexpression of angiotensinogen, which develop Ang II-mediated cardiac hypertrophy in the absence of hemodynamic overload. Electrophysiological techniques, photolysis of caged Ca(2+) and confocal Ca(2+) imaging were used to examine ECC remodeling at early ( approximately 20 weeks of age) and late ( approximately 60 weeks of age) time points during the development of cardiac dysfunction. In young TG mice, increased cardiac Ang II levels induced a hypertrophic response in cardiomyocyte, which was accompanied by an adaptive change of Ca(2+) signaling, specifically an upregulation of the Na(+)/Ca(2+) exchanger-mediated Ca(2+) transport. In contrast, maladaptation was evident in older TG mice, as suggested by reduced sarcoplasmic reticulum Ca(2+) content resulting from a shift in the ratio of plasmalemmal Ca(2+) removal and sarcoplasmic reticulum Ca(2+) uptake. This was associated with a conserved ECC gain, consistent with a state of hypersensitivity in Ca(2+)-induced Ca(2+) release. Together, our data suggest that chronic elevation of cardiac Ang II levels significantly alters cardiomyocyte ECC in the long term, and thereby contractility, independently of hemodynamic overload and arterial hypertension.
Prostatic carcinogenesis evoked by cellular interaction.
Authors: L W Chung, S M Chang, C Bell, H Zhau, J Y Ro, A C von Eschenbach
Journal: Environmental Health Perspectives (1988)

Inoculation of tumorigenic prostatic stroma and nontumorigenic prostatic epithelia into the subcutaneous space of syngeneic rats induced the development of carcinosarcoma. The induced tumors, which were composed of a mixture of adenocarcinoma and fibrosarcoma, were androgen responsive. This model offers a novel mechanism for prostatic carcinogenesis in which prostatic fibroblasts determine epithelial growth, androgen responsiveness, and tumorigenicity. Our results emphasize the potential importance of an epigenetic pathway in prostatic carcinogenesis.
Correlation of circulating von Willebrand factor levels with cardiovascular hemodynamics.
Authors: W F Penny, M Weinstein, E W Salzman, J A Ware
Journal: Circulation (1991)

BACKGROUND Valvular heart disease is associated with a decreased platelet circulating time and a thrombotic tendency. The possibility that these events are related to changes in von Willebrand factor (vWF), a multimeric glycoprotein released from endothelial cells and platelets that mediates platelet adhesion to the vascular subendothelium, has not been examined. METHODS AND RESULTS We measured the vWF antigen (vWF:Ag) concentration in 43 patients undergoing cardiac catheterization for the evaluation of mitral (n = 17) or aortic (n = 10) stenosis or nonvalvular heart disease (n = 16). Mean vWF:Ag concentration was significantly higher in patients with mitral stenosis than in those without (212 +/- 84 versus 150 +/- 79 units/dl, p less than 0.02); this elevation was associated with a significant elevation of pulmonary vascular resistance (PVR) in the patients with mitral stenosis (186 +/- 49 versus 133 +/- 81 dynes-sec-cm-5, p less than 0.02). The vWF:Ag levels in the entire group of patients (regardless of the presence or type of valvular disease) varied directly with PVR (r = 0.72, p less than 0.0001) and with pulmonary artery pressure (r = 0.60, p less than 0.0001) and inversely with cardiac output (r = 0.64, p less than 0.0001). Changes in PVR, pulmonary artery pressure, or cardiac output could not be correlated with circulating levels of fibrinogen or beta-thromboglobulin, which may be released from activated platelets, nor with the endothelial cell product tissue plasminogen activator. CONCLUSIONS The association of high vWF:Ag levels with increased PVR and decreased cardiac output in patients both with and without mitral stenosis suggests a hemodynamically induced increase in the endothelial release of vWF, which might contribute to a thrombotic tendency in these patients.
Tissue measurements in senile sebaceous gland hyperplasia
Authors: P. KUMAR, S.P. BARTON, R. MARKS
Journal: British Journal of Dermatology (1988)

Journal Article Tissue measurements in senile sebaceous gland hyperplasia Get access P. KUMAR, P. KUMAR Department of Medicine (Dermatology), University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, U.K. Search for other works by this author on: Oxford Academic Google Scholar S.P. BARTON, S.P. BARTON Department of Medicine (Dermatology), University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. MARKS R. MARKS Department of Medicine (Dermatology), University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, U.K. Professor R.Marks, Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 118, Issue 3, 1 March 1988, Pages 397–402, https://doi.org/10.1111/j.1365-2133.1988.tb02434.x Published: 01 March 1988
Modulation of tissue plasminogen activator biosynthesis by phosphatidylinositol liposomes in human fetal lung fibroblasts
Authors: S. Floru, A. Gelvan, R. Maran, A. Kadouri, A. M. Cohen
Journal: American Journal of Hematology (1991)

Abstract Phosphatidylinositol (PI) liposomes at 40 μM increased tissue plasminogen activator (t‐PA) biosynthesis by human fetal lung fibroblasts IMR‐90 (FLF), after 5 days of incubation by 7.4 ± 1.4 times of the control level. Other phospholipid liposomes, such as phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylglycerol (PG), had no effect on t‐PA biosynthesis by FLF. The induction of t‐PA biosynthesis by PI liposomes was inhibited by specific inhibitors of phosphoinositide pathway: gentamycin and lithium chloride. Thus, gentamycin inhibited the effect of PI liposomes on t‐PA biosynthesis by 76% (P &lt; 0.001), while it had no effect on control FLF. Likewise, lithium chloride inhibited t‐PA biosynthesis of both PI‐treated and control FLF by &gt;84%. The induction of t‐PA biosynthesis by PI liposomes was dependent on RNA transcription and independent of DNA biosynthesis.
The Epidemiology of Chronic Rheumatism
Authors: J. S. Lawrence
Journal: Annals of the Rheumatic Diseases (1964)

The human hand is a fascinating subject, an actor of many roles and disguises: the man in miniature, revealing its owner's story.Here is a book which sets out to teach us how best to examine it.This book has had an immediate appeal to everyone who has seen it.All doctors are, from time to time, called upon to see patients quickly, when facilities and time for a full general examination are missing.A guide to what could be regarded as "how-not-to-miss-systemic-diseasewithout-undressing-the-patient" will obviously have a wide market.The book is excellently printed, beauti- ully bound, and most of the pictures are clear and com-
Dapsone, Trimethoprim, and Sulfamethoxazole Plasma Levels during Treatment of Pneumocystis Pneumonia in Patients with the Acquired Immunodeficiency Syndrome (AIDS)
Authors: Belle L. Lee
Journal: Annals of Internal Medicine (1989)

Study Objective: To examine the interaction between dapsone and trimethoprim in patients with the acquired immunodeficiency syndrome (AIDS). Design: Measurement of drug levels as part of an open study of dapsone alone and randomized, double-blind comparison of trimethoprim-dapsone with trimethoprim-sulfamethoxazole in treating Pneumocystis carinii pneumonia in patients with AIDS. Setting: County hospital and AIDS clinic. Patients: Eighteen patients treated with dapsone alone, 30 with trimethoprim-dapsone, and 30 with trimethoprim-sulfamethoxazole. Intervention: Dapsone, 100 mg/d; trimethoprim, 20 mg/kg body weight per day, and sulfamethoxazole, 100 mg/kg · d; administered for 21 days. Measurements and Main Results: Concentrations of dapsone were 40% higher in patients treated with trimethoprim-dapsone than in those treated with dapsone alone (2.1 compared with 1.5 µg/mL; P < 0.05). Trimethoprim-dapsone-treated patients had fewer treatment failures but more side effects and treatment terminations due to toxicity than those treated with dapsone alone. The concentration of trimethoprim was 48.4% higher in patients treated with trimethoprim-dapsone than in those treated with trimethoprim-sulfamethoxazole, (18.4 compared with 12.4 µg/mL; P < 0.05). Discontinuation of therapy due to toxicity was commoner in the trimethoprim-sulfamethoxazole group (57% compared with 30%). Conclusions: A bidirectional drug interaction exists between dapsone and trimethoprim, resulting in higher concentrations of each in the presence of the other.
Myelopoietic effect of bone marrow fibroblasts cultured from patients with myelofibrosis
Authors: Jen C. Wang
Journal: American Journal of Hematology (1988)

Abstract Bone marrow fibroblasts (BMF) have been shown to be able to support granulopoiesis. The present studies were designed to see whether BMF in patients with agnogenic myeloid metaplasia (AMM) are also able to support granulopoiesis. Myeloid colonystimulating activity (CSA) was assayed in BMF derived from the three groups of patients. 1) Group I: Patients with hip fracture but without underlying hematological disease; patients with solid tumor but without bone marrow metastasis; and patients with iron deficiency anemia. 2) Group II: Patients with myeloproliferative disorders other than AMM. 3) Group III: Patients with AMM or myelofibrosis with prior history of polycythemia vera. CSA was determined in a bilayer agar culture system inwhich BMF served as a feeder layer and either mouse or human marrow cells were employed as target cells. There was no difference of CSA production by BMF among these three patient groups. These studies suggest that BMF cultured from patients with myelofibrosis exhibit similar myeloid stimulating activity as do BMF from other patients. A significant correlation was also found between CSA production by BMF and white blood cell counts in patients with myelofibrosis (group III). This suggests that BMF may have a role in either supporting or producing CSA for granulopoiesis in myelofibrosis.
Intrinsic and extrinsic mechanisms contribute to maintain the JAK/STAT pathway aberrantly activated in T-type large granular lymphocyte leukemia
Authors: Antonella Teramo, Cristina Gattazzo, Francesca Passeri, Albana Lico, Giulia Tasca, Anna Cabrelle, Veronica Martini, Federica Frezzato, Valentina Trimarco, Elisa Ave, Elisa Boscaro, Francesco Piazza, Monica Facco, Livio Trentin, Gianpietro Semenzato, Renato Zambello
Journal: Blood (2013)
Two immunogenic passenger dendritic cell subsets in the rat liver have distinct trafficking patterns and radiosensitivities
Authors: Bin Yu, Hisashi Ueta, Yusuke Kitazawa, Toshiya Tanaka, Kensuke Adachi, Hiromitsu Kimura, Miwa Morita, Yasushi Sawanobori, Hai Xin Qian, Tatsuhiko Kodama, Kenjiro Matsuno
Journal: Hepatology (2012)

The aim of this study was to investigate the trafficking patterns, radiation sensitivities, and functions of conventional dendritic cell (DC) subsets in the rat liver in an allotransplantation setting. We examined DCs in the liver, hepatic lymph, and graft tissues and recipient secondary lymphoid organs after liver transplantation from rats treated or untreated by sublethal irradiation. We identified two distinct immunogenic DC subsets. One was a previously reported population that underwent blood-borne migration to the recipient's secondary lymphoid organs, inducing systemic CD8+ T-cell responses; these DCs are a radiosensitive class II major histocompatibility complex (MHCII)+CD103+CD172a+CD11b−CD86+ subset. Another was a relatively radioresistant MHCII+CD103+CD172a+CD11b+CD86+ subset that steadily appeared in the hepatic lymph. After transplantation, the second subset migrated to the parathymic lymph nodes (LNs), regional peritoneal cavity nodes, or persisted in the graft. Irradiation completely eliminated the migration and immunogenicity of the first subset, but only partly suppressed the migration of the second subset and the CD8+ T-cell response in the parathymic LNs. The grafts were acutely rejected, and intragraft CD8+ T-cell and FoxP3+ regulatory T-cell responses were unchanged. The radioresistant second subset up-regulated CD25 and had high allostimulating activity in the mixed leukocyte reaction, suggesting that this subset induced CD8+ T-cell responses in the parathymic LNs and in the graft by the direct allorecognition pathway, leading to the rejection. Conclusion: Conventional rat liver DCs contain at least two distinct immunogenic passenger subsets: a radiosensitive blood-borne migrant and a relatively radioresistant lymph-borne migrant. LNs draining the peritoneal cavity should be recognized as a major site of the intrahost T-cell response by the lymph-borne migrant. This study provides key insights into liver graft rejection and highlights the clinical implications of immunogenic DC subsets. (Hepatology 2012)