tbuckley/cabot-search huggingface dataset:
Beta Adrenergic Receptors of Polymorphonuclear Particulates in Bronchial Asthma
Authors: Stanley P. Galant, Lakshmi Duriseti, Sharon Underwood, Sandra Allred, Paul A. Insel
Journal: Journal of Clinical Investigation (1980)

We have tested the beta adrenergic receptor theory of bronchial asthma by determining the number and affinity of binding sites of the beta adrenergic radioligand [(3)H]dihydroalprenolol (DHA) and the activity of adenylate cyclase in broken cell preparations of polymorphonuclear leukocytes (PMN). We studied 31 control subjects (group 1), 30 asthmatics receiving no systemic adrenergic medication (group 2), and 17 asthmatics receiving adrenergic agonists systemically (group 3). Control subjects and asthmatics taking no adrenergic drugs bound similar amounts of DHA at 0.5 nM and 30 nM DHA and had about 900 binding sites per PMN. In contrast, asthmatics receiving adrenergic agonists had a >70% decrease in their number of DHA binding sites per PMN (254+/-57). In a subset of our three groups of subjects (eight from group 1, six from group 2, and five from group 3) we measured DHA binding at several DHA concentrations and found similar values (0.4-0.7 nM) for the dissociation constant of DHA among these subjects. In further studies we examined the interaction of the agonist (-)-isoproterenol with beta adrenergic receptors in 8 normal subjects and 10 asthmatics not receiving adrenergic medication. We tested the ability of isoproterenol to compete for DHA binding sites and to stimulate adenylate cyclase in sonicates prepared from PMN and examined under identical conditions. The dissociation constants for the competition of isoproterenol for DHA binding sites in normal and asthmatic subjects were virtually identical ( approximately 1.0 muM). In addition, the (activation constant) values for stimulation of adenylate cyclase were similar (0.16-0.19 muM) in the two groups of subjects.Thus, these data suggest that asthma per se is not associated with alteration in either the number or affinity of beta adrenergic receptors in PMN. Our findings indicate that previous reports of abnormal beta adrenergic receptor function in asthmatic patients may in part be explained by prior treatment of such patients with adrenergic agonists. Because the asthmatics who received adrenergic agonists in our study tended to be more ill and to receive additional medication compared to subjects in group 2, we cannot rule out unequivocally that severe asthma may be associated with decreased binding to beta adrenergic receptors. Nevertheless, we conclude that beta adrenergic receptors on PMN from asthmatics are relatively normal unless such patients are treated with adrenergic agonists.
Caveolin 1 Is Overexpressed and Amplified in a Subset of Basal-like and Metaplastic Breast Carcinomas: A Morphologic, Ultrastructural, Immunohistochemical, and <i>In situ</i> Hybridization Analysis
Authors: Kay Savage, Maryou B.K. Lambros, David Robertson, Robin L. Jones, Chris Jones, Alan Mackay, Michelle James, Jason L. Hornick, Emilio M. Pereira, Fernanda Milanezi, Christopher D.M. Fletcher, Fernando C. Schmitt, Alan Ashworth, Jorge S. Reis-Filho
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The distribution and significance of caveolin 1 (CAV1) expression in different breast cell types and role in breast carcinogenesis remain poorly understood. Both tumor-suppressive and oncogenic roles have been proposed for this protein. The aims of this study were to characterize the distribution of CAV1 in normal breast, benign breast lesions, breast cancer precursors, and metaplastic breast carcinomas; to assess the prognostic significance of CAV1 expression in invasive breast carcinomas; and to define whether CAV1 gene amplification is the underlying genetic mechanism driving CAV1 overexpression in breast carcinomas. Experimental Design: CAV1 distribution in frozen and paraffin-embedded whole tissue sections of normal breast was evaluated using immunohistochemistry, immunofluorescence, and immunoelectron microscopy. CAV1 expression was immunohistochemically analyzed in benign lesions, breast cancer precursors, and metaplastic breast carcinomas and in a cohort of 245 invasive breast carcinomas from patients treated with surgery followed by anthracycline-based chemotherapy. In 25 cases, CAV1 gene amplification was assessed by chromogenic in situ hybridization. Results: In normal breast, CAV1 was expressed in myoepithelial cells, endothelial cells, and a subset of fibroblasts. Luminal epithelial cells showed negligible staining. CAV1 was expressed in 90% of 39 metaplastic breast carcinomas and in 9.4% of 245 invasive breast cancers. In the later cohort, CAV1 expression was significantly associated with ‘basal-like’ immunophenotype and with shorter disease-free and overall survival on univariate analysis. CAV1 gene amplification was found in 13% of cases with strong CAV1 expression. Conclusions: The concurrent CAV1 amplification and overexpression call into question its tumor-suppressive effects in basal-like breast carcinomas.
Longer-Term Assessment of Trastuzumab-Related Cardiac Adverse Events in the Herceptin Adjuvant (HERA) Trial
Authors: Marion Procter, Thomas M. Suter, Evandro de Azambuja, Urania Dafni, Veerle van Dooren, Susanne Muehlbauer, Miguel Angel Climent, Ernst Rechberger, Walter Tsang-Wu Liu, Mazakasu Toi, R. Charles Coombes, David Dodwell, Olivia Pagani, Jorge Madrid, Marcia Hall, Shin-Cheh Chen, Christian Focan, Michael Muschol, Dirk J. van Veldhuisen, Martine J. Piccart-Gebhart
Journal: Journal of Clinical Oncology (2010)

We investigated the incidence of cardiac adverse events in patients with early breast cancer in the Herceptin Adjuvant (HERA) trial who were treated with 1 year of trastuzumab after completion of (neo)adjuvant chemotherapy.The HERA trial is a three-group, randomized trial that compared 1 year or 2 years of trastuzumab with observation in women with human epidermal growth factor receptor-2 (HER2) -positive early breast cancer. Eligible patients had normal left ventricular ejection fraction (LVEF; >or= 55%) after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Cardiac function was monitored throughout the trial. This analysis considers patients randomly assigned to 1 year of trastuzumab treatment or observation.There were 1,698 patients randomly assigned to observation and 1,703 randomly assigned to 1 year of trastuzumab treatment; 94.1% of patients had been treated with anthracyclines. The incidence of discontinuation of trastuzumab because of cardiac disorders was low (5.1%). At a median follow-up of 3.6 years, the incidence of cardiac end points remained low, though it was higher in the trastuzumab group than in the observation group (severe CHF, 0.8% v 0.0%; confirmed significant LVEF decreases, 3.6% v 0.6%) In the trastuzumab group, 59 of 73 patients with a cardiac end point reached acute recovery; of these 59 patients, 52 were considered by the cardiac advisory board (CAB) to have a favorable outcome from the cardiac end point.The incidence of cardiac end points remains low even after longer-term follow-up. The cumulative incidence of any type of cardiac end point increases during the scheduled treatment period of 1 year, but it remains relatively constant thereafter.
Long-Term Prediction of Prostate Cancer Up to 25 Years Before Diagnosis of Prostate Cancer Using Prostate Kallikreins Measured at Age 44 to 50 Years
Authors: Hans Lilja, David Ulmert, Thomas Björk, Charlotte Becker, Angel M. Serio, Jan-Åke Nilsson, Per-Anders Abrahamsson, Andrew J. Vickers, Göran Berglund
Journal: Journal of Clinical Oncology (2007)

Purpose We examined whether prostate-specific antigen (PSA) forms and human kallikrein 2 (hK2) measured at age 44 to 50 years predict long-term risk of incident prostate cancer. Methods From 1974 to 1986, 21,277 men age ≤ 50 years in Malmö, Sweden, enrolled onto a cardiovascular study (74% participation). The rate of PSA screening in this population is low. According to the Swedish Cancer Registry, 498 were later diagnosed with prostate cancer. We measured hK2, free PSA, and total PSA (tPSA) in archived blood plasma from 462 participants later diagnosed with prostate cancer and from 1,222 matched controls. Conditional logistic regression was used to test for association of prostate cancer with hK2 and PSA forms measured at baseline. Results Median delay between venipuncture and prostate cancer diagnosis was 18 years. hK2 and all PSA forms were strongly associated with prostate cancer (all P &lt; .0005). None of the 90 anthropometric, lifestyle, biochemical, and medical history variables measured at baseline was importantly predictive. A tPSA increase of 1 ng/mL was associated with an increase in odds of cancer of 3.69 (95% CI, 2.99 to 4.56); addition of other PSA forms or hK2 did not add to the predictive value of tPSA. tPSA remained predictive for men diagnosed ≥ 20 years after venipuncture, and the predictive value remained unchanged in an analysis restricted to palpable disease. Conclusion A single PSA test at age 44 to 50 years predicts subsequent clinically diagnosed prostate cancer. This raises the possibility of risk stratification for prostate cancer screening programs.
Ten-year follow-up of percutaneous transluminal coronary angioplasty for proximal left anterior descending coronary artery stenosis in 351 patients
Authors: Jurriën M. ten berg, Melvyn Tjon Joe Gin, Sjef M.P.G. Ernst, Johannes C. Kelder, Maarten Jan Suttorp, E. Gijs Mast, Egbert Bal, H.W. Thijs Plokker
Journal: Journal of the American College of Cardiology (1996)
Vitamin D counteracts fibrogenic TGF-β signalling in human hepatic stellate cells both receptor-dependently and independently
Authors: Anja Beilfuss, Jan-Peter Sowa, Svenja Sydor, Mechthild Beste, Lars P Bechmann, Martin Schlattjan, Wing-Kin Syn, Inga Wedemeyer, Zoltan Mathé, Christoph Jochum, Guido Gerken, Robert K Gieseler, Ali Canbay
Journal: Gut (2014)

Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity and constitutes part of the metabolic syndrome, which have been associated with low serum vitamin D (VD). Due to known crosstalk between VD and transforming growth factor (TGF)-β signalling, VD has been proposed as an antifibrotic treatment.We evaluated the association between VD, the vitamin D receptor (VDR) and liver fibrosis in primary human hepatic stellate cells (phHSC) and 106 morbidly obese patients with NAFLD.Treating phHSC with VD ameliorated TGF-β-induced fibrogenesis via both VDR-dependent and VDR-independent mechanisms. Reduction of fibrogenic response was abolished in cells homozygous for GG at the A1012G single nucleotide polymorphisms within the VDR gene. Compared with healthy livers, NAFLD livers expressed higher levels of VDR mRNA and VDR fragments. VDR mRNA was lower in patients homozygous for GG at A1012G and expression of pro-fibrogenic genes was higher in patients carrying the G allele.VD may be an antifibrotic treatment option early in the onset of fibrosis in specific genotypes for VDR. Known polymorphisms of the VDR may influence the response to VD treatment.
Selective Cyclooxygenase-1 and -2 Inhibitors Each Increase Allergic Inflammation and Airway Hyperresponsiveness in Mice
Authors: R. Stokes Peebles, Koichi Hashimoto, Jason D. Morrow, Ryszard Dworski, Robert D. Collins, Yuko Hashimoto, John W. Christman, Kyung-Ho Kang, Kasia Jarzecka, Jamye Furlong, Daphne B. Mitchell, Megha Talati, Barney S. Graham, James R. Sheller
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Nonselective cyclooxygenase (COX) inhibition during allergic sensitization with ovalbumin in a murine model leads to an increase in the Type 2 cytokines interleukin-5 (IL-5) and IL-13; however, the effect of selective COX-1 and COX-2 inhibitors on these cytokines is unknown. We found that COX-1 protein was constitutively expressed in lung tissue. Expression of COX-1 protein did not increase with ovalbumin sensitization, but expression of COX-2 protein did. Ovalbumin-sensitized mice treated with either selective COX-1 inhibitor SC58560 (OVA-COX-1 inhibitor) or selective COX-2 inhibitor SC58236 (OVA-COX-2 inhibitor) had significantly greater airway hyperresponsiveness (p < 0.05) and higher levels of IL-13 (p < 0.05) in lung supernatants than did untreated mice that were ovalbumin sensitized (OVA). Lung mRNA levels for the chemokine receptors CCR1 through CCR5 (expressed on eosinophils, basophils, lymphocytes, and dendritic cells) were increased in the OVA-COX-2 inhibitor and OVA-indomethacin groups. We conclude that in the BALB/c mouse, COX inhibition with either a COX-1 or COX-2 inhibitor during allergen sensitization augments production of IL-13 and increases airway hyperresponsiveness.
Efficacy of the Branched-Chain Amino Acids in the Treatment of Tardive Dyskinesia in Men
Authors: Mary Ann Richardson, Margaret L Bevans, Laura L Read, Helen M Chao, James D Clelland, Raymond F Suckow, Timothy J Maher, Leslie Citrome
Journal: American Journal of Psychiatry (2003)

The efficacy of the branched-chain amino acids in the treatment of tardive dyskinesia in men with psychiatric disorders was tested.Public-sector psychiatric patients with long histories of antipsychotic treatment and presumably long-standing tardive dyskinesia were randomly assigned to receive branched-chain amino acids or placebo. Treatment frequency was three times a day, 7 days a week for 3 weeks. The efficacy measure was a frequency count of videotaped tardive dyskinesia movements.A robust and highly significant difference was observed between patients who received high-dose branched-chain amino acids (222 mg/kg of body weight t.i.d.) (N=18) and those who received placebo (N=18) in the percent change in tardive dyskinesia symptoms from baseline to the end of the 3-week trial. Significant and marked differences were seen between the two groups at the >/=30% and >/=60% levels of decrease in tardive dyskinesia symptoms. No clinically significant differences were seen between the pre- and posttrial results of physical examinations and laboratory screening tests. Minimal gastrointestinal symptoms occurred during the trial. The reduction in tardive dyskinesia symptoms in the amino acids group was not related to changes in antipsychotic and glucose plasma levels. A mechanism of response related to decreased amine neurotransmitter synthesis was suggested by the significant positive correlations observed between decreases in tardive dyskinesia symptoms and decreases in aromatic amino acid plasma concentrations over the course of the trial.Branched-chain amino acids constitute a novel, safe treatment for tardive dyskinesia, with a strong potential for providing significant improvement in the diseased physiognomy of the afflicted person.
Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma
Authors: Yulong Chen, Masahiko Terajima, Yanan Yang, Li Sun, Young-Ho Ahn, Daniela Pankova, Daniel S. Puperi, Takeshi Watanabe, Min P. Kim, Shanda H. Blackmon, Jaime Rodriguez, Hui Liu, Carmen Behrens, Ignacio I. Wistuba, Rosalba Minelli, Kenneth L. Scott, Johannah Sanchez-Adams, Farshid Guilak, Debananda Pati, Nishan Thilaganathan, Alan R. Burns, Chad J. Creighton, Elisabeth D. Martinez, Tomasz Zal, K. Jane Grande-Allen, Mitsuo Yamauchi, Jonathan M. Kurie
Journal: Journal of Clinical Investigation (2015)

Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde–derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde–derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma.
Septicemia in the United States Dialysis Population, 1991 to 1999
Authors: Robert N. Foley, Haifeng Guo, Jon J. Snyder, David T. Gilbertson, Allan J. Collins
Journal: Journal of the American Society of Nephrology (2004)

<h3>Abstract</h3> Lipidoid nanoparticles (LNPs) are the delivery platform in Onpattro, the first FDA-approved siRNA drug. LNPs are also the carriers in the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines. While these applications have demonstrated that LNPs effectively deliver nucleic acids to hepatic and muscle cells, it is unclear if LNPs could be used for delivery of siRNA to neural cells, which are notoriously challenging delivery targets. Therefore, the purpose of this study was to determine if LNPs could efficiently deliver siRNA to neurons. Because of their potential utility in either applications in the central nervous system and the peripheral nervous system, we used both cortical neurons and sensory neurons. We prepared siRNA-LNPs using C12-200, a benchmark ionizable cationic lipidoid along with helper lipids. We demonstrated using dynamic light scattering that the inclusion of both siRNA and PEG-lipid provided a stabilizing effect to the LNP particle diameters and polydispersity indices by minimizing aggregation. We found that siRNA-LNPs were safely tolerated by primary dorsal root ganglion neurons. Flow cytometry analysis revealed that Cy5 siRNA delivered via LNPs into rat primary cortical neurons showed uptake levels similar to Lipofectamine RNAiMAX—the gold standard commercial transfection agent. However, LNPs demonstrated a superior safety profile whereas the Lipofectamine-mediated uptake was concomitant with significant toxicity. Fluorescence microscopy demonstrated a time-dependent increase in the uptake of LNP-delivered Cy5 siRNA in a human cortical neuron cell line. Overall, our results suggest that LNPs are a viable platform that can be optimized for delivery of therapeutic siRNAs to neural cells.
Correction: What Are the Roles and Responsibilities of the Media in Disseminating Health Information?
Authors: Gary Schwitzer, Ganapati Mudur, David Henry, Amanda Wilson, Merrill Goozner, Maria Simbra, Melissa Sweet, Katherine A Baverstock
Journal: PLoS Medicine (2005)

The following sentence contains an incorrect number: "Only by massaging the numbers could one fi gure out that physicians would need to put 700 women on statins to eliminate one cancer case (in medical parlance, this is called number needed to treat)."The corrected sentence is as follows: "Only by massaging the numbers could one fi gure out that physicians would need to put 140 women on statins to eliminate one cancer case (in medical parlance, this is called number needed to treat).
Thoracentesis outcomes: a 12-year experience
Authors: Mark J Ault, Bradley T Rosen, Jordan Scher, Joe Feinglass, Jeffrey H Barsuk
Journal: Thorax (2014)

<h3>Background</h3> Despite a lack of evidence in the literature, several assumptions exist about the safety of thoracentesis in clinical guidelines and practice patterns. We aimed to evaluate specific demographic and clinical factors that have been commonly associated with complications such as iatrogenic pneumothorax, re-expansion pulmonary oedema (REPE) and bleeding. <h3>Methods</h3> We performed a cohort study of inpatients who underwent thoracenteses at Cedars-Sinai Medical Center (CSMC) from August 2001 to October 2013. Data were collected prospectively including information on volume of fluid removed, procedure side, whether the patient was on positive pressure ventilation, number of needle passes and supine positioning. Iatrogenic pneumothorax, REPE and bleeding were tracked for 24 h after the procedure or until a clinical question was reconciled. Demographic and clinical characteristics were obtained through query of electronic medical records. <h3>Results</h3> CSMC performed 9320 inpatient thoracenteses on 4618 patients during the study period. There were 57 (0.61%) iatrogenic pneumothoraces, 10 (0.01%) incidents of REPE and 17 (0.18%) bleeding episodes. Iatrogenic pneumothorax was significantly associated with removal of &gt;1500 mL fluid (p&lt;0.0001), unilateral procedures (p=0.001) and more than one needle pass through the skin (p=0.001). For every 1 mL of fluid removed there was a 0.18% increased risk of REPE (95% CI 0.09% to 0.26%). There were no significant associations between bleeding and demographic or clinical variables including International Normalised Ratio, partial thromboplastin time and platelet counts. <h3>Conclusions</h3> Our series of thoracenteses had a very low complication rate. Current clinical guidelines and practice patterns may not reflect evidence-based best practices.
Restenosis after coronary angioplasty: The paradox of increased lumen diameter and restenosis
Authors: Kevin J. Beatt, Patrick W. Serruys, Hans E. Luijten, Benno J. Rensing, Haryanto Suryapranata, Pim de Feyter, Marcel van den Brand, Gert Jan Laarman, Jos Roelandt, Gerrit Anne van ES
Journal: Journal of the American College of Cardiology (1992)
EPIDEMIC JAUNDICE OF CHILDREN IN 1852, WITH METEOROLOGICAL CHANGES DURING THAT PERIOD
Authors: T. H. Barker
Journal: BMJ (1854)

DiNO the months of September, October, and November of 1852, so many cases of jaundice in children, v ing from a year and a hlf to ten years of age, came under my notice, as to lead to the supposition that the diseae was epidemic.This opinion was confirmed on ascertaining that the same frequency was observed by other medical practi- tioners in this town and neighbourhood.The disease has been so similar in all the cases which have occurred in my practice, that the details of the follow- ing case will serve as a specimen of all of them.CAsi.L. E. B., aged nine and a half years, came under my care on the 2nd of November.She laboured under general in- isposition and languor; complaining of headache, chilliness, loss of appetite, and of a feeling of uneasiness in the epi- gastric region, accompanied with nausea.She had lost her natural buoyancy of spirits, and was peevish, fretful, and restless.The tongue was coated with white fur; she was somewhat thirsty; the skin was hot and dry; the bowels were constipated; and the urine was scanty and high coloured.There was no abdominal enlargement.She was ordered a foot-bath at night, a light farinaceous diet, and the following medicine:- & Hydr.chlorid., Iulv.jalapce, an gr.iij.M.Fiat pulvis