tbuckley/cabot-search huggingface dataset:
Increased Expression of Mineralocorticoid Effector Mechanisms in Kidney Biopsies of Patients With Heavy Proteinuria
Authors: Marcus Quinkler, Daniel Zehnder, Kevin S. Eardley, Julia Lepenies, Alexander J. Howie, Susan V. Hughes, Paul Cockwell, Martin Hewison, Paul M. Stewart
Journal: Circulation (2005)

Background— Aldosterone has emerged as a deleterious hormone in the heart, with mineralocorticoid receptor (MR) blockade reducing mortality in patients with severe heart failure. There is also experimental evidence that aldosterone contributes to the development of nephrosclerosis and renal fibrosis in rodent models, but little is known of its role in clinical renal disease. Methods and Results— We quantified MR, serum- and glucocorticoid-regulated kinase 1 (sgk1), and mRNA expression of inflammatory mediators such as macrophage chemoattractant protein-1 (MCP-1), transforming growth factor-β1, and interleukin-6 in 95 human kidney biopsies in patients with renal failure and mild to marked proteinuria of diverse etiologic origins. We measured renal function, serum aldosterone, urinary MCP-1 protein excretion, and the amount of chronic renal damage. Macrophage invasion was quantified by CD68 and vascularization by CD34 immunostaining. Serum aldosterone correlated negatively with creatinine clearance ( P &lt;0.01) and positively with renal scarring ( P &lt;0.05) but did not correlate with MR mRNA expression or proteinuria. Patients with heavy albuminuria (&gt;2 g/24 h; n=15) had the most renal scarring and the lowest endothelial CD34 staining. This group showed a significant 5-fold increase in MR, a 2.5-fold increase in sgk1 expression and a significant increase in inflammatory mediators (7-fold increase in MCP-1, 3-fold increase in transforming growth factor-β1, and 2-fold increase in interleukin-6 mRNA). Urinary MCP-1 protein excretion and renal macrophage invasion were significantly increased in patients with heavy albuminuria. Conclusions— These studies support animal data linking aldosterone/MR activation to renal inflammation and proteinuria. Further studies are urgently required to assess the potential beneficial effects of MR antagonism in patients with renal disease.
Transient adhesion of neutrophils to endothelium.
Authors: S K Lo, P A Detmers, S M Levin, S D Wright
Journal: The Journal of Experimental Medicine (1989)

Fluorescently labeled polymorphonuclear leukocytes (PMN) were used to measure adhesion to human umbilical vein endothelial cells (EC) cultured in vitro. Stimulation of PMN with phorbol dibutyrate (PDB), TNF, or C5a caused an increase in adhesion followed by a return to prestimulation levels of adhesion of longer times of incubation. Maximal adhesion of PMN to EC occurred rapidly in response to C5a (5 min) and more slowly with TNF or PDB (15 min). PMN stimulated to adhere with C5a detached from EC by 15 min. PMN from CD11/CD18-deficient patients and PMN incubated with anti-CD18 mAbs failed to bind to EC despite maximal stimulation. Anti-CD11a/CD18 and anti-CD11b/CD18 each partially inhibited adhesion, and a combination of these two reagents completely blocked adhesion. The adhesion we measured was therefore completely dependent on CD11/CD18, and CD11a/CD18 and CD11b/CD18 each contributed to adhesion. Stimuli that enhanced adhesion of PMN to EC also enhanced expression of CD11b/CD18 on the cell surface, but the time course of expression correlated poorly with changes in adhesivity. To determine if changes in the expression of CD11b/CD18 are necessary for the changes in adhesivity, we used enucleate cytoplasts that did not increase expression of CD11b/CD18. Cytoplasts showed a normal rise and fall in adhesivity in response to PDB. We conclude that the transient adhesion of stimulated PMN to naive EC is regulated by changes in the nature of existing CD11/CD18 molecules on the PMN surface. Changes in expression of CD11b/CD18 may contribute to enhancement of adhesivity, but a definite role for this phenomenon has yet to be established.
Consistently low hepatitis B virus-DNA saves patients from hepatocellular carcinogenesis in HBV-related cirrhosis
Authors: Kenji Ikeda, Masahiro Kobayashi, Yasuji Arase, Takashi Someya, Satoshi Saitoh, Yoshiyuki Suzuki, Fumitaka Suzuki, Akihito Tsubota, Norio Akuta, Hiromitsu Kumada
Journal: Journal of Hepatology (2002)
RADIOTHERAPY AS A METHOD OF IDENTIFYING CERTAIN VARIETIES OF TUMOR
Authors: ARTHUR U. DESJARDINS
Journal: JAMA (1933)

Among the methods of identifying and classifying tumors, microscopic examination has for a long time stood preeminent. Until now, in fact, it has been the only method by which substantial accuracy in the identification of neoplasms can be achieved. Without microscopic examination the classification of new growths would be as rudimentary as it was before the development of microscopic pathology. From the standpoint of science in general and medicine in particular, the microscope undoubtedly is one of the most valuable instruments ever invented. If microscopic examination of diseased tissue does not invariably lead to accurate identification of lesions benign or malignant, the fault does not lie with the instrument but with the human observer, the accuracy of whose observations and deductions depends on the quality of the optical system of the microscope, the acuity of his own vision, the range and depth of his knowledge of pathology and other phases
THE THERAPEUTIC ACTION OF CHLOROFORM IN PARTURITION.
Authors: BEDFORD BROWN
Journal: JAMA (1895)

The results of chloroform anesthesia in parturition constitute one of the most remarkable and interesting features in the history of medicine. During the past thirty-five years there have doubtless been millions of cases of parturition in which the agency of chloroform as an anesthetic has been called into requisition in the civilized world with the rarest report of fatal consequences. Then too, when we take into consideration the manner in which chloroform is given in labor, often recklessly, carelessly, and copiously, we are still further astonished at the almost universally favorable results. Often administered by ignorant nurses, husbands, bystanders, even by the patients themselves, and not infrequently, recklessly and injudiciously by the attending physicians, it is wonderful that evil results are so rare. Thus chloroform is used in a manner in parturition that no surgeon would dare to do in performing an operation. The profession has come to regard the
Role of Endothelin-1 in Beagles With Dehydromonocrotaline-Induced Pulmonary Hypertension
Authors: Morihito Okada, Chojiro Yamashita, Masayoshi Okada, Kenji Okada
Journal: Circulation (1995)

Background Although plasma levels of endothelin-1 (ET-1) increase in patients with pulmonary hypertension (PH), its role in PH is unknown. We investigated the contribution of endogenous ET-1 to cardiopulmonary changes in beagles with dehydromonocrotaline (DMCT)-induced PH. Methods and Results Eight 3-month-old beagles were given a single injection of 3 mg/kg DMCT via the right atrium. During the 8 weeks after injection, the mean pulmonary arterial pressure (PAP) and plasma ET-1 level increased significantly from 11.6±2.3 to 35.9±7.1 mm Hg and from 1.24±0.25 to 3.25±0.94 pg/mL, respectively. In controls, ET-1 infusion elevated the systemic arterial pressure (SAP) but did not alter PAP. In PH beagles, ET-1 infusion increased SAP, which was attenuated by FR139317 (an endothelin type [ET] A receptor antagonist), and produced a dose-dependent decrease in PAP, which was attenuated by RES-701-1 (an ETB receptor antagonist). In PH beagles, FR139317 infusion decreased PAP, and RES-701-1 infusion increased PAP. Sarafotoxin S6c (an ETB agonist) infusion decreased PAP in PH beagles. Conclusions These results suggest that endogenous ET-1 is elevated in PH disease and may mitigate PH by acting on ETB receptors.
Inorganic pyrophosphate in plasma in normal persons and in patients with hypophosphatasia, osteogenesis imperfecta, and other disorders of bone
Authors: R. G. G. Russell, S. Bisaz, A. Donath, D. B. Morgan, H. Fleisch
Journal: Journal of Clinical Investigation (1971)

An isotope dilution method, using (32)P-labeled pyrophosphate, has been developed for the measurement of inorganic pyrophosphate (PP(1)) in human plasma. The specificity of the method was better than 90% as assessed by elution patterns during ion-exchange chromatography, by paper chromatography, and by incubation with inorganic pyrophosphatase. The 99% confidence limits for a single estimation of plasma PP(1) was +/-13%. There were no differences in plasma PP(1) between men and women, but the values in young people (0-15 yr) were slightly higher than in older people. The mean concentration (+/-SE) of PP(1) in the plasma of 73 men and women was 3.50 +/-0.11 mumoles/liter (0.217 +/-0.007 mug P/ml) and the normal range (99% limits) was 1.19-5.65 mumoles/liter (0.074-0.350 mug P/ml). It has been suggested that PP(1) may be important in calcium metabolism because PP(1) can prevent the precipitation of calcium phosphates in vitro and in vivo, and can slow the rates at which hydroxyapatite crystals grow and dissolve. Plasma PP(1) was therefore measured in several disorders of bone. Normal values were found in osteogenesis imperfecta, osteopetrosis, "acute" osteoporosis, and primary hyperparathyroidism. Plasma PP(1) was invariably raised in hypophosphatasia. The excess of PP(1) in plasma might be the cause of the defective mineralization in hypophosphatasia and the function of alkaline phosphatase in bone may be to act as a pyrophosphatase at sites of calcium deposition.
Abstract 728: Development of pharmacophore-based RET inhibitors for thyroid cancer therapy
Authors: Jui-wen Huang, Ching-Huai Ko, Ting-Shou Chen, On Lee, Hsiang-Wen Tseng, Yuan-Jang Tsai, Chih-Peng Liu, Yen-Chun Chen, Ling-Mei Wang, Chrong-Shiong Hwang
Journal: Cancer Research (2010)

Abstract The new therapeutic option is pivotal due to the restricted efficacy of current treatments (surgery, radioactive iodine treatment, and chemotherapy) in progressive thyroid carcinomas. Gain-of-function mutations of the receptor tyrosine kinase RET have been identified as driving oncogenic events in subsets of papillary and medullary thyroid cancers (PTC and MTC), but targeted therapy for RET-driven cancers is currently clinically unavailable. Some mulit-kinase inhibitors, such as sunitinib and vandetanib, which have shown efficacy against other neoplastic diseases, are being evaluated in clinical trials for thyroid cancer therapy. However, the anti-VEGFR activities of these mulit-kinase inhibitors have been considered to lead cardiotoxicity in some patients. Moreover, Ret mutation-associated resistance have been reported by some RET inhibitors in preclinical data. The “in silico model” was applied to design the specific RET target compounds through mapping the pharmacophore of RET ATP-binding pocket. Some novel scaffold compounds which fit the pharmacophore model were selected form ITRI library, and their anti-RET activities were evaluated by kinase assay. The in vitro anti-cell proliferation activities of the compounds to the TT cells (MTC specific cells) were demonstrated by MTT assay. From the screening of ITRI library, ITRI-305 showed the impressive anti-RET (IC50 ∼ 90 nM) and anti-cell proliferation (IC50 at low micro molar) activities and the activities are compatible to those of sunitinib and vandetanib. ITRI-305 also shows good solubility and favorable oral PK profiles. The xenograft study of TT cells with ITRI-305 is proceeding. In conclusion, a novel scaffold RET inhibitor, ITRI-305, with less potent VEGFR activity (anti-VEFGR IC50 ∼ 1 μM) is developed to overcome the cardiotoxicity and resistance problems which is caused by conventional RET inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 728.
Origin of the Lamina Propria Dendritic Cell Network
Authors: Milena Bogunovic, Florent Ginhoux, Julie Helft, Limin Shang, Daigo Hashimoto, Melanie Greter, Kang Liu, Claudia Jakubzick, Molly A. Ingersoll, Marylene Leboeuf, E. Richard Stanley, Michel Nussenzweig, Sergio A. Lira, Gwendalyn J. Randolph, Miriam Merad
Journal: Immunity (2009)
Scintigraphic assessment of osteoarthritis of the knee joint.
Authors: F McCrae, J Shouls, P Dieppe, I Watt
Journal: Annals of the Rheumatic Diseases (1992)

Clinical, radiographic, and scintigraphic abnormalities of the knee joint have been correlated in a cross sectional study of 100 patients with osteoarthritis. The group comprised 73 women and 27 men with a mean age of 65.7 years. One hundred and ninety one of the 200 knees had clinical (175) or radiographic (185) evidence of osteoarthritis, or both (161). Scintigraphic images of the knees were obtained 4-5 minutes (early phase) and 2.5-3.5 hours (late phase) after intravenous injection of 600 mBq of technetium-99m diphosphonate. Abnormal images were recorded in 162 knees (81%), and six different patterns were detected. Generalised isotope retention around the knee (early or late phase) was less common than focal areas of uptake around the joint margin (early or late phase) or in the patella or subchondral bone (late phase). Some knees with abnormal scans were normal on radiography (n = 7), or vice versa (n = 21). Different scan patterns correlated with different clinical and radiographic features: the generalised pattern correlated with pain (odds ratio (OR) = 45.1) and osteophytes (OR = 48.3); joint line retention correlated with subchondral bone sclerosis on radiography (OR = 62.1); and subchondral bone retention correlated with more severe radiographic changes. It is concluded that different patterns of scintigraphic abnormality reflect various aspects of the disease process of osteoarthritis.
Inhibition of c-Src Tyrosine Kinase Prevents Angiotensin II–Mediated Connexin-43 Remodeling and Sudden Cardiac Death
Authors: Ali A. Sovari, Shahriar Iravanian, Elena Dolmatova, Zhe Jiao, Hong Liu, Shadi Zandieh, Vibhash Kumar, Kun Wang, Kenneth E. Bernstein, Marcelo G. Bonini, Heather S. Duffy, Samuel C. Dudley
Journal: Journal of the American College of Cardiology (2011)
MicroRNA Expression Profiles Associated With Prognosis and Therapeutic Outcome in Colon Adenocarcinoma
Authors: Aaron J. Schetter, Suet Yi Leung, Jane J. Sohn, Krista A. Zanetti, Elise D. Bowman, Nozomu Yanaihara, Siu Tsan Yuen, Tsun Leung Chan, Dora L. W. Kwong, Gordon K. H. Au, Chang-Gong Liu, George A. Calin, Carlo M. Croce, Curtis C. Harris
Journal: JAMA (2008)

Amajor cause of cancer mortality worldwide. 1Colorectal cancer is the third most common and second leading cause of cancer death in the United States. 2 Even though 5-year mortality rates have modestly declined over the last 3 decades, 3 there is still a need to identify new prognostic biomarkers and therapeutic targets for this disease.Currently, chemotherapy has significant therapeutic value, but surgery is the only curative form of treatment. 4deal therapeutic targets should be causally associated with disease and amenable to designing therapeutic interventions, whereas ideal biomarkers should be easy to measure and have strong associations with clinical outcomes.Mi-croRNAs could match both criteria.
Disease-Specific Survival of Men With Prostate Cancer Detected During the Screening Interval: Results of the European Randomized Study of Screening for Prostate Cancer–Rotterdam After 11 Years of Follow-Up
Authors: Xiaoye Zhu, Pim J. van Leeuwen, Meelan Bul, Suzie J. Otto, Harry J. de Koning, Chris H. Bangma, Fritz H. Schröder, Monique J. Roobol
Journal: European Urology (2011)
Diagnostic Value of FDG PET and Salivary Gland Scintigraphy for Parotid Tumors
Authors: Yoshitaka Uchida, Satoshi Minoshima, Tetsuya Kawata, Ken Motoori, Koichi Nakano, Toshiki Kazama, Takashi Uno, Yoshitaka Okamoto, Hisao Ito
Journal: Clinical Nuclear Medicine (2005)

Purpose: The purpose of this study was to examine the diagnostic value of the combination of F-18 fluorodeoxyglucose (FDG) PET and Tc-99m pertechnetate salivary gland scintigraphy in parotid tumors. Materials and Methods: Seventy-two patients with benign parotid gland tumors (n = 52), malignant parotid tumors (n = 12), and inflammation (n = 8) underwent both FDG PET and salivary gland scintigraphy within 1 week, and 66 of the patients also underwent gallium scintigraphy. All patients were negative on their first fine-needle aspiration (FNA). Results: Malignant parotid tumors showed significantly higher FDG uptake (standard uptake values [SUVs]) than both benign tumors and inflammation, except in Warthin's tumor (5.82 ± 3.95 vs. 2.07 ± 1.33; P <0.01). Although the SUV values of Warthin's tumor and malignant parotid tumors overlapped somewhat, Warthin's tumor did demonstrate increased radiotracer uptake, and it was reliably distinguished from other parotid gland tumors by the use of salivary gland scintigraphy. Considering a SUV value >3 as being positive for malignancy and excluding Warthin's tumor on the basis of salivary gland scintigraphy, sensitivity and specificity of FDG PET were 75% and 80%, respectively. These results were superior to those of gallium scintigraphy (58% and 72%, respectively). Conclusions: Although the diagnostic value of FDG PET in the differentiation of malignant from benign parotid gland tumors was limited because of the high FDG uptake in some benign tumors, and particularly pleomorphic adenomas, combining salivary gland scintigraphy with FDG PET may help to negate this drawback, and this combination may be a more promising approach for differentiation of various parotid gland tumors in patients compared with nondiagnostic needle aspiration.
OUTCOMES AFTER REVASCULARIZATION WITH EVEROLIMUS AND SIROLIMUS ELUTING STENTS IN PATIENTS WITH SMALL AND LARGE CORONARY ARTERIES. A SUBSTUDY OF THE SORT OUT IV TRIAL
Authors: Lisbeth Antonsen, Lisette Okkels Jensen, Per Thayssen, Evald H&oslash;j Christiansen, Michael Maeng, Hans-Henrik Tilsted, Jan Ravkilde, Anne Kaltoft, Henrik Hansen, Morten Madsen, Leif Thuesen, Jens Lassen
Journal: Journal of the American College of Cardiology (2012)
THE DISTRIBUTION OF FE59 TAGGED HUMAN ERYTHROCYTES IN CENTRIFUGED SPECIMENS AS A FUNCTION OF CELL AGE
Authors: E. Raymond Borun, William G. Figueroa, Seymour M. Perry
Journal: Journal of Clinical Investigation (1957)

This study demonstrates that the density of human erythrocytes increases with age and that cell populations with different mean ages can be isolated on the basis of this density gradient.The data suggest that the concentration of Fe59 in the bottom layer of centrifuged erythrocyte specimens may be used to estimate the mean life span of ageing cells. METHODSSix to ten microcuries of Fe were administered intravenously to eight hematologically normal subjects who had various chronic diseases (Table I).Five of the subjects received Fe iron globulin complex ' and three received Few ferrous citrate1 that had been incubated with the subject's plasma or whole blood before injection.Specific activity of both preparations was 0.5 to 1.5 mC. per mgm.at the time of administration.One subject (C.A.) 2 also received 100 ,uC. of Cr' (1).Twenty ml.heparinized blood specimens were drawn at the intervals indicated in Figure 1 and centrifuged in 10-ml.plastic tubes for 40 minutes at 3,000 RPM (approximately 2,000 G.).The tubes were placed in an alcohol-dry ice freezing mixture for a few minutes and were then cut 1 to 2 mm.below the plasma-erythrocyte interface.The bottom portions containing the frozen erythrocytes were cut into four equal sections.The radioactivity of thawed aliquots from each section was measured in a well-type scintillation counter with a Ti- activated NaI crystal and expressed as counts per second per ml. of erythrocytes.The Fe'3 and Cr' activity in specimens from C.A. were measured separately by dif- ferential pulse height analysis (1).Correction for iso- tope decay was based on the radioactivity of standards which were prepared from the injected material and counted with each blood specimen.The standard error of the counting procedure was less than + 2 per cent for most specimens and less than ±4 per cent for the low activity specimens.
Quantification of Blo t 5 in mite and dust extracts by two‐site ELISA
Authors: F. C. Yi, B. W. Lee, N. Cheong, K. Y. Chua
Journal: Allergy (2004)

Background: Blomia tropicalis is an important mite species in the tropical and sub‐tropical regions of the world. Blo t 5 is the major allergen with up to 70% sensitization rates in B. tropicalis allergic populations. Methods: Mice were immunized intramuscularly with naked plasmid DNA encoding Blo t 5 gene with in vivo electroporation. Blo t 5 monoclonal antibodies were generated using methylcellulose‐based hybridoma kit. Monoclonal antibody (mAb) 4A7 was characterized by two‐dimensional electrophoresis immunoblotting. A specific quantitative two‐site enzyme‐linked immunosorbent assay (ELISA) was developed with mAb 4A7 and guinea pigs Blo t 5 polyclonal antibody as capture and detection antibodies, respectively. This system was tested with Blo t 5 in crude extracts and dust samples. Results: A high‐affinity mAb 4A7 recognizing several isoforms of Blo t 5 has been generated. Monoclonal antibody 4A7 is useful for immunoblotting and two‐site ELISA. The two‐site ELISA developed has a high sensitivity, with a detection limit of 10 pg/ml. The assay is species‐specific and recognized the same epitopes on both native and recombinant Blo t 5. The assay developed is able to detect Blo t 5 in commercial diagnostic and therapeutic B. tropicalis extract. Blo t 5 quantification in dust samples showed that Blo t 5 is present in a high quantity in Singapore dust. Conclusions: A highly sensitive and specific two‐site ELISA has been developed. The assay system developed is useful for the quantification of Blo t 5 in mite and environmental dust extracts.