tbuckley/cabot-search huggingface dataset:
THE PREPARATION OF CRYSTALLINE BILIRUBIN-C14*
Authors: J. Donald Ostrow, Lydia Hammaker, Rudi Schmid
Journal: Journal of Clinical Investigation (1961)

Conventional methods for measuring small amounts of bilirubin in biological material, based on the diazo reaction (1-3), have frequently proved unsatisfactory because of relative insensi- tivity at low pigment concentrations (2, 4-6), problems encountered in standardization (7-9), and loss of pigment through attachment to pre- cipitated protein (1-3).Furthermore, while a small group of tetrapyrrolic chromogens derived from bilirubin can be estimated by their color re- action with p-dimethylaminobenzaldehyde (Ehr- lich reagent) (10, 11), methods of analysis and quantitation are almost completely lacking for Ehrlich-negative pyrrole compounds (12, 13).These methodological shortcomings have hin- dered adequate study of several important aspects of bile pigment metabolism including: the mode of bilirubin transport in the serum at physiological concentrations (14-18), the mechanism of bili- rubin exchange between serum and tissue pro- teins (19, 20), the rate of conversion of bilirubin to non-urobilinoid catabolites (13, 21), and the nature and magnitude of the enterohepatic circu- lation of bile pigments (22, 23).Clarification of these problems has awaited preparation of radio- isotopically labeled bilirubin of high specific ac- tivity.Possible approaches for introducing a radio- active label into the bilirubin molecule include chemical synthesis from opsopyrrolecarboxylic acid-C14 (24), tritiation by the Wilzbach tech- nique (25), and biosynthesis from glycine-2-C14 (26).Of these, only the last method seemed technically feasible.The present paper describes a biosynthetic prep- aration of radiochemically pure bilirubin-C14 of high specific activity.It involves administration
An uncommon reason for dyspnoea: phrenic paresis secondary to alveolar echinococcosis
Authors: Philipp Wassmer, Joannis Chronis, Jochen J. Rüdiger, Katia Boggian
Journal: European Respiratory Journal (2012)

To the Editors:

We describe the presentation of an Echinococcus multilocularis (EM) infection (alveolar echinococcosis (AE)) with progressive massive orthopnoea and progressive dyspnoea on exertion due to infiltration of the diaphragm and phrenic nerves. Diagnosis was proved using a combination of computed tomography (CT), lung function in the supine and sitting position, sniff test during radioscopy and AE serology. Because of diffuse infiltration of the retroperitoneal and mediastinal space a surgical intervention was inapplicable. Thus, medical treatment was initiated using albendazole. Noninvasive ventilation (NIV) resolved orthopnoea and the patient was discharged.

AE occurs in the northern hemisphere but in Switzerland it is classified as a rare disease. To our knowledge this is the first described case of this rare infection with a consecutive bilateral paresis of the diaphragm. But despite its unique entity, this case report demonstrates that clinical findings and routine diagnostic methods may lead to the correct diagnosis.

Progressive phrenic paresis is a rare cause of orthopnoea and dyspnoea on exertion [1]. Relevant paresis is often overseen and diagnosed late in the course of the disease. The main reasons for bilateral phrenic paresis are traumatic, inflammatory, neuropathic, idiopathic or tumour related [1]. We present a case of a non-malignant compression caused by AE leading to bilateral phrenic paresis.

A 60-yr-old farmer’s wife presented to a district hospital with progressive dyspnoea on exertion for 2 yrs. A cardiologic consultation at that time including echocardiography and exercise testing was unremarkable. Within the last year, the patient complained about weight …
Hepatocyte Growth Factor Modulates Matrix Metalloproteinases and Plasminogen Activator/Plasmin Proteolytic Pathways in Progressive Renal Interstitial Fibrosis
Authors: Rujun Gong, Abdalla Rifai, Evelyn M Tolbert, Jason N Centracchio, Lance D Dworkin
Journal: Journal of the American Society of Nephrology (2003)

Evidence suggests that hepatocyte growth factor (HGF) ameliorates renal fibrosis in animal models of chronic renal disease by promoting extracellular matrix catabolism. This study examined the molecular mechanisms of HGF-induced alterations in matrix degradation both in vitro and in vivo. In vitro, HGF increased the collagen catabolizing activity of human proximal tubular epithelial cells (HKC) that were treated with TGF-beta1. Increased collagen catabolism was associated with enhanced activity of both matrix metalloproteinases (MMP) and plasminogen activators (PA)/plasmin proteolytic pathways. HGF abrogated TGF-beta1-induced production of the profibrotic tissue inhibitor of metalloproteinase-2 (TIMP-2) and plasminogen activator inhibitor-1 (PAI-1). In addition, HGF induced the production of MMP-9. In vivo, continuous infusion of HGF in the rat remnant kidney model ameliorated renal fibrosis and tubulointerstitial collagen deposition. This was associated with increased tubular expression of MMP-9, enhanced in situ gelatinolytic activity, partially restored plasmin activity and decreased expression of TIMP-2 and PAI-1 in tubular cells, and upregulation of renal TIMP-3 expression. Conversely, blocking of endogenous HGF by an anti-HGF neutralizing antibody increased renal fibrosis and interstitial collagen. This was accompanied by decreased tubular expression of MMP-9, less in situ proteolytic activity, and elevated expression of TIMP-2 and PAI-1 in tubular cells. Collectively, these findings demonstrate that HGF ameliorates renal fibrosis by enhancing extracellular matrix catabolism via both MMP and the PA/plasmin proteolytic pathways.
Treatment of severe erythrodermic acute graft-versus-host disease with photochemotherapy
Authors: M. Kunz, S. Wilhelm, M. Freund, R. Zimmermann, G. Gross
Journal: British Journal of Dermatology (2001)

Journal Article Treatment of severe erythrodermic acute graft‐versus‐host disease with photochemotherapy Get access M. Kunz, M. Kunz Departments of Dermatology and Venereology and Internal Medicine, Medical Oncology, University of Rostock, 18055 Rostock, Germany Search for other works by this author on: Oxford Academic Google Scholar S. Wilhelm, S. Wilhelm Departments of Dermatology and Venereology and Internal Medicine, Medical Oncology, University of Rostock, 18055 Rostock, Germany Search for other works by this author on: Oxford Academic Google Scholar M. Freund, M. Freund Departments of Dermatology and Venereology and Internal Medicine, Medical Oncology, University of Rostock, 18055 Rostock, Germany Search for other works by this author on: Oxford Academic Google Scholar R. Zimmermann, R. Zimmermann Departments of Dermatology and Venereology and Internal Medicine, Medical Oncology, University of Rostock, 18055 Rostock, Germany Search for other works by this author on: Oxford Academic Google Scholar G. Gross G. Gross Departments of Dermatology and Venereology and Internal Medicine, Medical Oncology, University of Rostock, 18055 Rostock, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 144, Issue 4, 1 April 2001, Pages 901–902, https://doi.org/10.1046/j.1365-2133.2001.04155.x Published: 01 April 2001
Cross sectional studies: advantages and disadvantages
Authors: P. Sedgwick
Journal: BMJ (2014)

<h3>Introduction</h3> Stroke is a frequent disease in the older population of Western Europe with aphasia as a common consequence. Aphasia is known to impede targeting treatment to individual patients’ needs and therefore may reduce treatment success. In Germany, the postacute care of patients who had stroke is provided by different healthcare institutions of different sectors (rehabilitation, nursing and primary care) with substantial difficulties to coordinate services. We will conduct two qualitative evidence syntheses (QESs) aiming at exploring distinct healthcare needs and desires of older people living with poststroke aphasia. We thereby hope to support the development of integrated care models based on needs of patients who are very restricted to communicate them. Since various methods of QESs exist, the aim of the study embedding the two QESs was to determine if findings differ according to the approach used. <h3>Methods and analysis</h3> We will conduct two QESs by using metaethnography (ME) and thematic synthesis (ThS) independently to synthesise the findings of primary qualitative studies. The main differences between these two methods are the underlying epistemologies (idealism (ME) vs realism (ThS)) and the type of research question (emerging (ME) vs fixed (ThS)). We will search seven bibliographical databases. Inclusion criteria comprise: patients with poststroke aphasia, aged 65 years and older, studies in German/English, all types of qualitative studies concerning needs and desires related to healthcare or the healthcare system. The protocol was registered in the International Prospective Register of Systematic Reviews, follows Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and includes three items from the Enhancing Transparency in Reporting the synthesis of Qualitative Research checklist. <h3>Ethics and dissemination</h3> Ethical approval is not required. Findings will be published in a peer-reviewed journal and presented on national conferences.
Ethambutol Ocular Toxicity in Treatment Regimens for <i>Mycobacterium avium</i> Complex Lung Disease
Authors: David E. Griffith, Barbara A. Brown-Elliott, Sara Shepherd, Jerry McLarty, Lee Griffith, Richard J. Wallace
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Ethambutol (EMB) is an important component of multidrug treatment regimens for Mycobacterium avium complex lung disease. Ocular toxicity is the most important potential EMB toxicity, especially in the elderly population with M. avium complex lung disease. Two hundred twenty-nine patients with M. avium complex lung disease, 55% women and 53% with nodular/bronchiectatic disease, received a mean of 16.1 ± 10.8 months of multidrug therapy that included EMB. Fifty patients (22%) were known to have preexisting ocular disease. While on EMB, 97 (42%) patients consulted an opthalmologist and 24 (10%) stopped EMB at least temporarily. Eight of 139 patients (6%) on daily therapy were diagnosed with EMB ocular toxicity, whereas 0 of 90 patients on intermittent therapy had EMB ocular toxicity (p = 0.05). All patients with EMB ocular toxicity developed symptoms between outpatient clinic appointments; none were diagnosed with routine visual acuity and color vision testing. All patients with EMB ocular disease returned to baseline ocular status after discontinuation of EMB. Intermittent EBM administration was associated with less ocular toxicity than daily EMB administration in this patient population.
Role of macrophage migration inhibitory factor in ovalbumin-induced airway inflammation in rats
Authors: M. Kobayashi, Y. Nasuhara, A. Kamachi, Y. Tanino, T. Betsuyaku, E. Yamaguchi, J. Nishihira, M. Nishimura
Journal: European Respiratory Journal (2006)

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that reportedly counteracts the anti-inflammatory effect of endogenous glucocorticoids. There have only been a few reports that demonstrate a potential link between MIF and bronchial asthma. In an attempt to further clarify the precise role of MIF in asthma, the present authors examined the effect of anti-MIF antibody (Ab) on airway inflammation and airway hyperresponsiveness in an ovalbumin-immunised rat asthma model. Actively immunised Brown Norway rats received ovalbumin inhalation with or without treatment of anti-MIF Ab. The levels of MIF in bronchoalveolar lavage fluid were significantly elevated after the ovalbumin challenge. An immunohistochemical study revealed positive immunostaining for MIF in bronchial epithelium, even in nonsensitised rats, and the MIF staining in bronchial epithelium was enhanced after the ovalbumin challenge. Anti-MIF Ab significantly decreased the number of total cells, neutrophils and eosinophils in the bronchoalveolar lavage fluid of the ovalbumin-challenged rats, and also attenuated the ovalbumin-induced airway hyperresponsiveness to ovalbumin and methacholine. However, anti-MIF Ab did not affect the level of serum ovalbumin-specific IgE, suggesting that anti-MIF Ab did not suppress immunisation itself. The results indicate that macrophage migration inhibitory factor plays a crucial role in airway inflammation and airway hyperresponsiveness in asthma.
The Glycolytic Enzyme, GPI, Is a Functionally Conserved Modifier of Dopaminergic Neurodegeneration in Parkinson’s Models
Authors: Adam L. Knight, Xiaohui Yan, Shusei Hamamichi, Rami R. Ajjuri, Joseph R. Mazzulli, Mike W. Zhang, J. Gavin Daigle, Siyuan Zhang, Akeem R. Borom, Lindsay R. Roberts, S. Kyle Lee, Susan M. DeLeon, Coralie Viollet-Djelassi, Dimitri Krainc, Janis M. O’Donnell, Kim A. Caldwell, Guy A. Caldwell
Journal: Cell Metabolism (2014)
Testosterone and Dihydrotestosterone Tissue Levels in Recurrent Prostate Cancer
Authors: Mark A. Titus, Michael J. Schell, Fred B. Lih, Kenneth B. Tomer, James L. Mohler
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Prostate cancer eventually recurs during androgen deprivation therapy despite castrate levels of serum androgens. Expression of androgen receptor and androgen receptor–regulated proteins suggests androgen receptor activation in recurrent prostate cancer. Many groups have pursued mechanisms of ligand-independent androgen receptor activation but we found high levels of testicular androgens in recurrent prostate cancer tissue using RIA. Experimental Designs: Prostate specimens from 36 men were procured preserving blood flow to prevent ischemia and cyropreserved immediately. Recurrent prostate cancer specimens from 18 men whose cancer recurred locally during androgen deprivation therapy and androgen-stimulated benign prostate specimens from 18 men receiving no hormonal treatments were studied. Tissue levels of testosterone and dihydrotestosterone were measured in each specimen using liquid chromatography/electrospray tandem mass spectrometry. Testosterone and dihydrotestosterone levels were compared with clinical variables and treatment received. Results: Testosterone levels were similar in recurrent prostate cancer (3.75 pmol/g tissue) and androgen-stimulated benign prostate (2.75 pmol/g tissue, Wilcoxon two-sided, P = 0.30). Dihydrotestosterone levels decreased 91% in recurrent prostate cancer (1.25 pmol/g tissue) compared with androgen-stimulated benign prostate (13.7 pmol/g tissue; Wilcoxon two-sided, P &amp;lt; 0.0001) although dihydrotestosterone levels in most specimens of recurrent prostate cancer were sufficient for androgen receptor activation. Testosterone or dihydrotestosterone levels were not related to metastatic status, antiandrogen treatment, or survival (Wilcoxon rank sum, all P &amp;gt; 0.2). Conclusions: Recurrent prostate cancer may develop the capacity to biosynthesize testicular androgens from adrenal androgens or cholesterol. This surprising finding suggests intracrine production of dihydrotestosterone and should be exploited for novel treatment of recurrent prostate cancer.
Calcium channels in muscle cells isolated from rat mesenteric arteries: modulation by dihydropyridine drugs.
Authors: B P Bean, M Sturek, A Puga, K Hermsmeyer
Journal: Circulation Research (1986)

The patch clamp technique was used to make whole-cell recordings of calcium channel currents from single muscle cells freshly isolated from rat mesenteric arteries. The cells were found to contain two types of calcium channels; one type is activated by small depolarizations and inactivates quickly, whereas the other requires stronger depolarizations for activation and inactivates more slowly. Nitrendipine blocked the second type of channels with a potency that depended on membrane potential. Interpreted by a modulated receptor hypothesis, these results suggest that nitrendipine binds to the inactivated state of the channel with a KD of about 0.5 nM, similar to concentrations effective in relaxing blood vessels. The magnitude of the calcium channel current was small compared with other excitable cells, but the "calcium agonist" drug BAY K8644 produced a 10-fold augmentation of calcium channel current, suggesting the existence of a large "reserve" of calcium channel current.
DDX31 Regulates the p53-HDM2 Pathway and rRNA Gene Transcription through Its Interaction with NPM1 in Renal Cell Carcinomas
Authors: Tomoya Fukawa, Masaya Ono, Taisuke Matsuo, Hisanori Uehara, Tsuneharu Miki, Yusuke Nakamura, Hiro-omi Kanayama, Toyomasa Katagiri
Journal: Cancer Research (2012)

Abstract Studies of renal cell carcinoma (RCC) have led to the development of new molecular-targeted drugs but its oncogenic origins remain poorly understood. Here, we report the identification and critical roles in renal carcinogenesis for DDX31, a novel nucleolar protein upregulated in the vast majority of human RCC. Immunohistochemical overexpression of DDX31 was an independent prognostic factor for patients with RCC. RNA interference (RNAi)-mediated attenuation of DDX31 in RCC cells significantly suppressed outgrowth, whereas ectopic DDX31 overexpression in human 293 kidney cells drove their proliferation. Endogenous DDX31 interacted and colocalized with nucleophosmin (NPM1) in the nucleoli of RCC cells, and attenuation of DDX31 or NPM1 expression decreased pre-ribosomal RNA biogenesis. Notably, in DDX31-attenuated cells, NPM1 was translocated from nucleoli to the nucleoplasm or cytoplasm where it bound to HDM2. As a result, HDM2 binding to p53 was reduced, causing p53 stablization with concomitant G1 phase cell-cycle arrest and apoptosis. Taken together, our findings define a mechanism through which control of the DDX31–NPM1 complex is likely to play critical roles in renal carcinogenesis. Cancer Res; 72(22); 5867–77. ©2012 AACR.
Framycetin sulphate (Soframycin) as a pre-operative bowel-sterilizing agent
Authors: A. G. Horsburgh
Journal: Gut (1961)

The author has investigated the bowel-sterilizing powers of framycetin sulphate, and has compared its potency with that of neomycin. He has found that the drug is well tolerated, and not toxic in doses which are sufficient to suppress faecal organisms satisfactorily.
Human blood-brain barrier receptors for Alzheimer's amyloid-beta 1- 40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer.
Authors: J B Mackic, M Stins, J G McComb, M Calero, J Ghiso, K S Kim, S D Yan, D Stern, A M Schmidt, B Frangione, B V Zlokovic
Journal: Journal of Clinical Investigation (1998)

A soluble monomeric form of Alzheimer's amyloid-beta (1-40) peptide (sAbeta1-40) is present in the circulation and could contribute to neurotoxicity if it crosses the brain capillary endothelium, which comprises the blood-brain barrier (BBB) in vivo. This study characterizes endothelial binding and transcytosis of a synthetic peptide homologous to human sAbeta1-40 using an in vitro model of human BBB. 125I-sAbeta1-40 binding to the brain microvascular endothelial cell monolayer was time dependent, polarized to the apical side, and saturable with high- and low-affinity dissociation constants of 7.8+/-1.2 and 52.8+/-6.2 nM, respectively. Binding of 125I-sAbeta1-40 was inhibited by anti-RAGE (receptor for advanced glycation end products) antibody (63%) and by acetylated low density lipoproteins (33%). Consistent with these data, transfected cultured cells overexpressing RAGE or macrophage scavenger receptor (SR), type A, displayed binding and internalization of 125I-sAbeta1-40. The internalized peptide remains intact > 94%. Transcytosis of 125I-sAbeta1-40 was time and temperature dependent, asymmetrical from the apical to basolateral side, saturable with a Michaelis constant of 45+/-9 nM, and partially sensitive to RAGE blockade (36%) but not to SR blockade. We conclude that RAGE and SR mediate binding of sAbeta1-40 at the apical side of human BBB, and that RAGE is also involved in sAbeta1-40 transcytosis.
Exercise Training Enhances Vasodilation Responses to Vascular Endothelial Growth Factor in Porcine Coronary Arterioles Exposed to Chronic Coronary Occlusion
Authors: Jennifer A. Fogarty, Judy M. Muller-Delp, Michael D. Delp, Mildred L. Mattox, M. Harold Laughlin, Janet L. Parker
Journal: Circulation (2004)

Chronic coronary occlusion (CCO) impairs endothelial function of distal collateral-dependent microvasculature; however, long-term exercise training (EX) seems to improve endothelial dysfunction. We hypothesized that EX enhances vasodilation responses to vascular endothelial growth factor (VEGF165), mediated via nitric oxide (NO), in arterioles exposed to CCO.The proximal left circumflex coronary artery (LCx) of female Yucatan miniswine was surgically instrumented with an ameroid occluder to induce CCO; 8 weeks after surgery, animals were randomized into 14-week sedentary (SED) or EX (treadmill; 5 d/wk) protocols. Coronary arterioles ( approximately 100 microm in diameter) were isolated from collateral-dependent (LCx) and nonoccluded (left anterior descending; LAD) perfused myocardium of SED and EX animals. Vasodilation was assessed by videomicroscopy and MacLab data acquisition. Responses to VEGF165 were unaffected by EX in nonoccluded LAD arterioles; in contrast, EX markedly enhanced VEGF165-induced vasodilation of collateral-dependent LCx arterioles (P<0.05; EX versus SED). Furthermore, VEGF165-induced vasodilation of EX LCx arterioles exceeded that of EX or SED LAD arterioles (P<0.05). Enhanced vasodilation of EX LCx arterioles was abolished by inhibition of NO synthase and tyrosine kinase activity. Combined inhibition of NO synthase and cyclooxygenase decreased VEGF165-induced vasodilation of all vessels.EX enhances VEGF165-induced vasodilation in arterioles distal to CCO; EX effects seem to be mediated through increases in NO.
Nck Proteins Maintain the Adult Glomerular Filtration Barrier
Authors: Nina Jones, Laura A. New, Megan A. Fortino, Vera Eremina, Julie Ruston, Ivan M. Blasutig, Lamine Aoudjit, Youling Zou, Xiuwen Liu, Guo-Liang Yu, Tomoko Takano, Susan E. Quaggin, Tony Pawson
Journal: Journal of the American Society of Nephrology (2009)

Within the glomerulus, the scaffolding protein nephrin bridges the actin-rich foot processes that extend from adjacent podocytes to form the slit diaphragm. Mutations affecting a number of slit diaphragm proteins, including nephrin, cause glomerular disease through rearrangement of the actin cytoskeleton and disruption of the filtration barrier. We recently established that the Nck family of Src homology 2 (SH2)/SH3 cytoskeletal adaptor proteins can mediate nephrin-dependent actin reorganization. Formation of foot processes requires expression of Nck in developing podocytes, but it is unknown whether Nck maintains podocyte structure and function throughout life. Here, we used an inducible transgenic strategy to delete Nck expression in adult mouse podocytes and found that loss of Nck expression rapidly led to proteinuria, glomerulosclerosis, and altered morphology of foot processes. We also found that podocyte injury reduced phosphorylation of nephrin in adult kidneys. These data suggest that Nck is required to maintain adult podocytes and that phosphotyrosine-based interactions with nephrin may occur in foot processes of resting, mature podocytes.