tbuckley/cabot-search huggingface dataset:
-adrenergic relaxation in pulmonary arteries: preservation of the endothelial nitric oxide-dependent 2 component in pulmonary hypertension
Authors: V. Leblais, E. Delannoy, F. Fresquet, H. Begueret, N. Bellance, S. Banquet, C. Allieres, L. Leroux, C. Desgranges, A. Gadeau, B. Muller
Journal: Cardiovascular Research (2007)

β-adrenoceptor (β-AR)-mediated relaxation was characterized in pulmonary arteries from normoxic and hypoxic (as model of pulmonary hypertension) mice. The endothelial NO synthase (eNOS) pathway was especially investigated because of its potential vasculoprotective effects. Pulmonary arteries from control or hypoxic (0.5 atm for 21 days) wild-type or eNOS−/− mice were used for pharmacological characterization of β-AR-mediated relaxation in myograph, and for immunohistochemistry using anti-β-AR antibodies. In pulmonary arteries from normoxic mice, isoproterenol (β-AR agonist) and procaterol (selective β2-AR agonist) elicited relaxation, while cyanopindolol and CL316243 (β3-AR agonists) were ineffective. The effect of isoproterenol was antagonized by CGP20712A and ICI118551 (β1- or β2-AR antagonists, respectively) and also partially inhibited by Nω-nitro-L-arginine methylester (L-NAME, a NOS inhibitor), endothelium denudation, or eNOS gene deletion. Relaxation to procaterol was abolished by L-NAME or endothelium removal. In eNOS−/− mice, procaterol-induced relaxation was decreased but was insensitive to L-NAME, this residual effect involving other endothelium-dependent relaxant factors as compensatory mechanisms. Immunostaining for β2-AR was observed in the endothelial layer, but not the medial layer of pulmonary arteries. Pulmonary arteries from hypoxic mice exhibited decreased endothelial NO-dependent relaxation to acetylcholine. However, in these arteries, relaxation to procaterol was either unaffected (extralobar segments) or even increased (intralobar segments) and was still abolished by L-NAME or endothelium removal. β1- and β2-AR, but not β3-AR, mediate relaxation of mice pulmonary arteries. The β2-AR component is dependent on eNOS activity and is preserved following chronic hypoxia. These data highlight the role of the β2-AR as a pharmacological target to induce/restore endothelial NO-dependent protective effects in pulmonary circulation.
Cyclophosphamide in systemic lupus erythematosus.
Authors: T Hadidi
Journal: Annals of the Rheumatic Diseases (1970)

Activation of protein kinase C (PKC) constitutes a key event in the upregulation of secretory strength in neurons and neurosecretory cells during extensive stimulation, presumably by speeding up vesicle supply. However, the molecular targets and their mode of action remain elusive. We studied the only PKC-dependent phosphorylation site in the neuronal soluble<i>N</i>-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, Ser<sup>187</sup>, in synaptosome-associated protein of 25 kDa (SNAP-25). This phosphorylation site is located within the negatively charged C-terminal end of SNAP-25, which has been shown to be of critical importance in calcium-triggered exocytosis. We combined mutational studies that used overexpression in chromaffin cells with capacitance measurements and flash photolysis of caged calcium, allowing for high time resolution during both the stimulation and measurement of exocytosis. Overexpression of mutants simulating the phosphorylated form of Ser<sup>187</sup> accelerated vesicle recruitment after the emptying of the releasable vesicle pools. Overexpression of mutants simulating the nonphosphorylated form, or block of PKC, impaired the refilling of the vesicle pools to similar extents. Biochemical studies verified the phosphorylation of a subpopulation of SNAP-25 after elevation of intracellular calcium concentrations. Some of the mutations led to a moderately decreased fast exocytotic burst component, which did not seem to be associated with the phosphorylation state of SNAP-25. Thus the C terminus of SNAP-25 plays a role for both fast exocytosis triggering and vesicle recruitment, and the latter process is regulated by PKC-dependent phosphorylation.
Lymphocyte Proliferative Response to P6 of<i>Haemophilus influenzae</i> Is Associated with Relative Protection from Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Yusuke Abe, Timothy F. Murphy, Sanjay Sethi, Howard S. Faden, Jacek Dmochowski, Yasuaki Harabuchi, Yasmin M. Thanavala
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Chronic obstructive pulmonary disease (COPD) is characterized by periodic exacerbations, some of which are caused by nontypeable Haemophilus influenzae (NTHI). P6 is an outer membrane lipoprotein that is highly conserved among strains of NTHI. We hypothesized that lymphocytes from patients with COPD who have exacerbations due to NTHI have a decreased ability to recognize P6. The in vitro lymphocyte proliferative response to P6 in 36 patients with COPD and 12 healthy control subjects was studied. Ten patients who had exacerbations due to NTHI in the previous 12 months showed statistically significant lower proliferation to P6 (stimulation index, log transformed mean ± standard error 0.82 ± 0.17) compared with 26 patients who had no exacerbations due to NTHI in the previous 12 months (1.42 ± 0.13) and to 12 healthy control subjects (1.61 ± 0.16). These three groups had no significant difference in the lymphocyte proliferative response to tetanus toxoid. There was no difference in serum antibody levels to P6 in the two groups with COPD. These results indicate that decreased proliferation of T cells to P6 is associated with exacerbations of COPD and suggest that the ability of T cells to recognize P6 is associated with relative protection from exacerbations due to NTHI.
Stress, LTP, and depressive disorder
Authors: I. C. Reid, C. A. Stewart
Journal: Behavioral and Brain Sciences (1997)

Preoccupation with LTP as a putative memory mechanism may have retarded the consideration of pathological modulation of synaptic plasticity in clinical disorders where memory dysfunction is not a primary feature. Encouraged by Shors &amp; Matzel's review, we consider the relationship between stress, synaptic plasticity, and depressive disorder.
Seasonal Local Allergic Rhinitis in Areas with High Exposure to Grass Pollen
Authors: F. de la Roca, N. Blanca-Lopez, C. Rondon, R. Herrera, J.L. Rodriguez-Bada, G. Canto, F. Feo Brito, M. Blanca Gomez
Journal: Journal of Allergy and Clinical Immunology (2012)
RESISTANCE TO SMALL DOSES OF INSULIN IN VARIOUS CLINICAL CONDITIONS 1
Authors: Norman S. Olsen, John A. Nuetzel
Journal: Journal of Clinical Investigation (1950)

In a number of clinical conditions the response of the level of blood sugar to a given dosage of insulin is less than that obtained in normal individuals.This phenomenon is commonly termed insu- lin resistance.Soon after the discovery of insulin numlerous investigators described resistance in certain cases of diabetes mellitus.Radoslav (1) in 1924 adminiistered known amounts of inisulin to fasting individuals suffering from diabetes mel- litus and pointed out that diabetics, without known comJplicationis, might be insulin resistant, inisulin sensitive, or insulin hypersensitive.The early investigations o01 this subject were comprehensively review-ed in 1933 (2); since that time, there have l)een numtierous reports describing insulin resistance in diabetes.Although the resistance has usually been attributed to various disorders complicating the diabetic state, certain cases exhibiting this phenomenon in marked degree have been unexplained (3).In 1941 Fraser, Albright, and Smith (4) demonstrated variations in response to the intravenous administration of 1/10 of a unit of insulin per kg. of body weight in a number of en- docrine disorders.The dosage recommended by these authors has been employed by other investi- gators to show insulin resistance in schizophrenics (5), pellagrins (6), and in a small group of hy- pertensives (7).Kronenberg and McCulloch (8), employing a uluch smaller dose, 1/40 unit per kg., demonstrated increased tolerance to in- sulin in oneirophrenics and in several cases of acromegaly and malignant hypertension.The present investigation explored this phenomenon in 99 patients suffering from hypertension and from other disease conditions, and in 25 normal subjects.The smaller dose of Kronenberg and
OECD validation of the Hershberger assay in Japan: phase 2 dose response of methyltestosterone, vinclozolin, and p,p'-DDE.
Authors: Kanji Yamasaki, Masakuni Sawaki, Ryo Ohta, Hirokazu Okuda, Seiichi Katayama, Tomoya Yamada, Takafumi Ohta, Tadashi Kosaka, William Owens
Journal: Environmental Health Perspectives (2003)

The Organisation for Economic Co-operation and Development has initiated the development of new guidelines for the screening and testing of potential endocrine disruptors. The Hershberger assay is one of the assays selected for validation based on the need for in vivo screening to detect androgen agonists or antagonists by measuring the response of five sex accessory organs and tissues of castrated juvenile male rats: the ventral prostate, the seminal vesicles with coagulating glands, the levator ani and bulbocavernosus muscle complex, the Cowper's glands, and the glans penis. The phase 1 feasibility demonstration stage of the Hershberger validation program has been successfully completed with a single androgen agonist and a single antagonist as reference substances. The phase 2 validation program employs a range of additional androgen agonists and antagonists as well as 5alpha-reductase inhibitors. Seven Japanese laboratories have contributed phase 2 validation studies of the Hershberger assay using methyltestosterone, vinclozolin, and 2,2-bis (4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE). The methyltestosterone doses were 0, 0.05, 0.5, 5, and 50 mg/kg/day, and the vinclozolin and p,p'-DDE doses were 0, 3, 10, 30, and 100 mg/kg/day. All chemicals were orally administered by gavage for 10 consecutive days. In the antagonist version of the assay using vinclozolin and p,p'-DDE, 0.2 mg/kg/day of testosterone propionate was coadministered by subcutaneous injection. All five accessory sex preproductive organs and tissues consistently responded with statistically significant changes in weight within a narrow window. Therefore, the Japanese studies support the Hershberger assay as a reliable and reproducible screening assay for the detection of androgen agonistic and antagonistic effects.
THE MEDICAL TREATMENT OF DUODENAL AND GASTRIC ULCER.
Authors: ALEXANDER LAMBERT
Journal: JAMA (1906)

To write a short discussion on the medical treatment of duodenal and gastric ulcer would have been a relatively simple task a few years ago; to-day it is far different and by no means easily performed. The difficulty arises in some degree because we realize more clearly than formerly that the course and prognosis of acute ulcer differ greatly from those of chronic ulcer, and especially because surgery has in a few years made such advances in the treatment of gastric ulcer that we must consider when medical treatment will suffice or when it is necessary for a surgeon to consider jointly what method of treatment will give the quickest and most permanent relief to the patient. The medical treatment of duodenal ulcer being practically the same as for gastric ulcer, what is said for one will apply also for the other. The acute and chronic gastric ulcer can not
Obesity and asthma: An association modified by age of asthma onset
Authors: Fernando Holguin, Eugene R. Bleecker, William W. Busse, William J. Calhoun, Mario Castro, Serpil C. Erzurum, Anne M. Fitzpatrick, Benjamin Gaston, Elliot Israel, Nizar N. Jarjour, Wendy C. Moore, Stephen P. Peters, Michael Yonas, W. Gerald Teague, Sally E. Wenzel
Journal: Journal of Allergy and Clinical Immunology (2011)
ALTERED FUNCTIONAL PROPERTIES OF THE RENAL GLOMERULUS IN AUTOLOGOUS IMMUNE COMPLEX NEPHRITIS
Authors: E. E. Schneeberger, P. D. Leber, M. J. Karnovsky, R. T. McCluskey
Journal: The Journal of Experimental Medicine (1974)

The altered functional properties of the glomerular capillary wall in a model of autologous immune complex disease (Heymann's nephritis) was studied by electron microscopy using intravenously injected protein tracers of varying molecular weight. There was an increase in the permeability of the glomerular basement membrane (GBM) itself to large molecules; this change was focal and was found in those areas where the GBM contained immune complex deposits. Both ferritin and catalase, tracers normally restricted from passing the glomerular filter, were present in the urinary space within minutes of injection. No evidence was obtained for increased glomerular epithelial transport in this disease. Foot process swelling and "close" junction formation was moderate, even in animals with marked degrees of proteinuria. Indirect evidence, therefore, makes an alteration in the slit pore complex likely. In addition, there was immediate and selective concentration of all tracers within deposits, though ferritin was partially excluded from some deposits. This phenomenon may be of significance in the perpetuation of the disease.
Clinicopathologic features of the intraductal growth type of peripheral cholangiocarcinoma
Authors: Kyung-Suk Suh, Hye Rin Roh, Young Taeg Koh, Kuhn Uk Lee, Yong-Hyun Park, Sun-Whe Kim
Journal: Hepatology (2000)

The clinicopathologic features of the intraductal growth (IG) type of peripheral cholangiocarcinoma (PCC) were examined retrospectively. Out of 112 patients who underwent surgery for PCC at Seoul National University Hospital, Seoul, Korea, between January 1980 and December 1997, 16 were classified as having the IG type. Thirteen were men and 3 were women. Their ages ranged from 38 to 73 years with a mean age of 55.9 years. Abdominal pain was the most common symptom and jaundice was found in 18.8%. Five patients had associated clonorchiasis and 6 patients experienced hepatolithiasis. Tumor sizes ranged from 0.5 cm to 14.0 cm with a mean of 4.3 cm. The tumor was located in the right lobe in 7 cases and the left lobe in 9 cases. Thirteen patients underwent major hepatic resection, and 3 underwent minor resection, involving a subsegmentectomy. Mucin was found in the bile in 4 cases. Pathology showed papillary adenocarcinoma with a background of adenomatous hyperplasia, and the absence of lymph node metastasis in all cases. The tumors were confined to the mucosa in 5 cases. Out of the 16 hepatic resections, 1 was palliative due to a positive margin. In 2 of the patients who underwent minor resections, recurrences developed, and 1 of these died 56 months after resection. Out of the 16 patients, 15 remain alive, ranging from 1 to 13 years, postoperatively. In conclusion, the IG type of PCC should be distinguished from other types of PCC because a favorable prognosis can be expected after complete surgical resection.
Dry Blood Test for Typhus
Authors: P. N. Bardhan, N. Tyagi, K. Boutros
Journal: BMJ (1944)

CADMIUM POISONING MEDICL JOIRNAL 253 48 hours should be insisted upon.In mild cases the symptoms by that time will have subsided, excepting possibly some nausea, anorexia, and weakness.In severe cases more prolonged recumbency is necessary, treatment being symptomatic and carried out according to general principles: oxygen for marked dyspnoea, sulphonamides for pneumonia, and appropriate sedatives for the dry cough and gastric disturbances.Mild cases recover in a few days; but when pneumonia ensues recovery is necessarily prolonged and disability may
Alcoholism: Its Facets and Phases
Authors: Marjorie C. Meehan
Journal: JAMA (1965)

Has any substance been productive of more pleasure and misery than alcohol? Can we compare its worth as tranquilizer, social lubricant, or euphoriant, with its role in causing lost jobs, unhappy homes, neglected children? How can we diminish the harm it causes without prohibiting its use to the majority who enjoy it safely? Although a relatively small proportion of those who drink do so to excess, it is estimated that there may be 5 million such alcoholics in the United States. Nobody knows how best to help them. Many feel that this is a medical problem, but most doctors dislike trying to treat heavy drinkers. A few physicians have worked very hard to help alcoholics and to investigate better ways of so doing. For years Marvin Block, MD, has been one of the leaders in this field. Block discusses, in terms suitable for lay readers of moderate intelligence, the entire
Efficacy of an Acellular Pertussis Vaccine among Adolescents and Adults
Authors: Joel I. Ward, James D. Cherry, Swei-Ju Chang, Susan Partridge, Hang Lee, John Treanor, David P. Greenberg, Wendy Keitel, Stephen Barenkamp, David I. Bernstein, Robert Edelman, Kathryn Edwards
Journal: New England Journal of Medicine (2005)

Pertussis immunization of adults may be necessary to improve the control of a rising burden of disease and infection. This trial of an acellular pertussis vaccine among adolescents and adults evaluated the incidence of pertussis, vaccine safety, immunogenicity, and protective efficacy.Bordetella pertussis infections and illnesses were prospectively assessed in 2781 healthy subjects between the ages of 15 and 65 years who were enrolled in a national multicenter, randomized, double-blind trial of an acellular pertussis vaccine. Subjects received either a dose of a tricomponent acellular pertussis vaccine or a hepatitis A vaccine (control) and were monitored for 2.5 years for illnesses with cough that lasted for more than 5 days. Each illness was evaluated with use of a nasopharyngeal aspirate for culture and polymerase-chain-reaction assay, and serum samples from patients in both acute and convalescent stages of illness were analyzed for changes in antibodies to nine B. pertussis antigens.Of the 2781 subjects, 1391 received the acellular pertussis vaccine and 1390 received the control vaccine. The groups had similar ages and demographic characteristics, and the median duration of follow-up was 22 months. The acellular pertussis vaccine was safe and immunogenic. There were 2672 prolonged illnesses with cough, but the incidence of this nonspecific outcome did not vary between the groups, even when stratified according to age, season, and duration of cough. On the basis of the primary pertussis case definition, vaccine protection was 92 percent (95 percent confidence interval, 32 to 99 percent). Among unimmunized controls with illness, 0.7 percent to 5.7 percent had B. pertussis infection, and the percentage increased with the duration of cough. On the basis of other case definitions, the incidence of pertussis in the controls ranged from 370 to 450 cases per 100,000 person-years.The acellular pertussis vaccine was protective among adolescents and adults, and its routine use might reduce the overall disease burden and transmission to children.
Abstract 5152: Mechanism and therapeutic potential of the histone demethylase GASC1 in castration-resistant prostate cancer
Authors: Roselyne M. Labbe, Qin Ye, Andreana Holowatyj, Lihong Zhang, Zeng Quan Yang
Journal: Cancer Research (2014)

Abstract The histone lysine demethylase, GASC1 (Gene Amplified in Squamous Cell Carcinoma 1) is an epigenetic regulatory protein both highly expressed during mammalian embryogenesis and overexpressed in several types of cancer, including aggressive Castration Resistant Prostate Cancer (CRPC). GASC1 mainly catalyzes demethylation of tri- and di-methylated forms of histone H3 lysine 9 (H3K9me3/me2) epigenetic repressive marks, regulating gene expression and chromatin architecture. This research aims to elucidate the fundamental mechanism by which GASC1 dysregulation contributes to CRPC progression, as well as to evaluate its potential as a therapeutic target against aggressive prostate cancer. Previously, our lab and others have shown that GASC1 interacts with the androgen receptor (AR) and functions as a co-activator of AR-induced transcription in prostate cancer. We have used an shRNA approach to determine whether GASC1 knockdown affects the proliferation and transformation of CRPC cells. We found that knocking down GASC1 inhibits the growth and colony formation of C4-2B and CWR22Rv1 cells in vitro. Knockdown also reduced transcript levels of classical and CRPC-specific AR target genes in either the presence or absence of the AR ligand. As a result, we are evaluating the therapeutic potential of novel and highly specific lysine demethylase inhibitors towards abating GASC1 function in prostate cancer cells in vitro. We have recently determined that one of these novel inhibitors is highly effective in modulating the survival and proliferation of several prostate cancer cell lines including CRPC lines with IC50 values, all well under 1 uM. Together, our data demonstrates that GASC1 is a therapeutically relevant target in controlling and preventing the emergence of prostate cancers, with particular application against aggressive CRPC subtypes. Citation Format: Roselyne M. Labbe, Qin Ye, Andreana Holowatyj, Lihong Zhang, Zeng Quan Yang. Mechanism and therapeutic potential of the histone demethylase GASC1 in castration-resistant prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5152. doi:10.1158/1538-7445.AM2014-5152
The Value of Phase 4 Clinical Testing
Authors: Gus J. Vlahakes
Journal: New England Journal of Medicine (2006)

Since its inception in 1988, the Multicenter Study of Perioperative Ischemia Research Group has examined a number of critical issues concerning the outcomes of cardiac surgery and anesthesia. The group's database is a powerful research tool. Its power derives from the high quality of the participating institutions, the capability of these institutions to recruit a large number of patients, and an absence of potential conflict of interest, in part due to the large number of participating institutions and investigators.In this issue of the Journal, Mangano et al.1 report the findings from a large clinical database built on the data-collection . . .
The Importance of the Family Environment in Pediatric Chronic Pain
Authors: Tonya M. Palermo, Amy Lewandowski Holley
Journal: JAMA Pediatrics (2012)

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