tbuckley/cabot-search huggingface dataset:
Luminal and Basolateral Membrane Transport of Glutathione in Isolated Perfused S1, S2, and S3 Segments of the Rabbit Proximal Tubule
Authors: LISA D. PARKS, RUDOLFS K. ZALUPS, DELON W. BARFUSS
Journal: Journal of the American Society of Nephrology (2000)

Lumen-to-bath and bath-to-lumen transport rates of glutathione (GSH) were measured in isolated perfused S(1), S(2), and S(3) segments of the rabbit proximal tubule. In lumen-to-bath experiments, the perfusion solution contained 4.6 microM (3)H-GSH with or without 1.0 mM acivicin. In all three segments perfused without acivicin, luminal disappearance rate (J(DL)) and bath appearance rate (J(AB)) of (3)H-GSH were 14.5 +/- 0.5 and 2.2 +/- 0.8 fmol/min per mm tubule length, respectively. With acivicin present, J(DL) and J(AB) were reduced to 1.3 +/- 0.4 and 0.5 +/- 0.3, respectively, with no differences among segments. Cellular concentrations of (3)H-GSH in S(1), S(2), and S(3) segments when acivicin was absent were 23.1 +/- 2.0, 31.7 +/- 11.4, and 143.5 +/- 17.9 microM, respectively. With acivicin in perfusate, cellular concentrations were reduced but there was no change in the heterogeneity profile. In bath-to-lumen transport experiments (S(2) segments only), the bathing solution contained 2.3 microM (3)H-GSH. (3)H-GSH appearance in the lumen (J(AL), fmol/min per mm) and cellular accumulation from the bath were studied with and without acivicin in the perfusate. J(AL) values were 3.0 +/- 0.2 and 0.2 +/- 0.03 while cellular concentrations were 9.5 +/- 1.0 and 6.1 +/- 0.5 microM, respectively. It is concluded that: (1) GSH is primarily removed from the luminal fluid after degradation to glycine, cysteine, and glutamate, which are absorbed; (2) GSH can be absorbed intact at the luminal membrane; (3) the S(3) segment has the greatest GSH cellular concentration because its basolateral membrane has less capacity for cell-to-bath transport of GSH; and (4) GSH can be secreted intact from the peritubular compartment into the tubular lumen.
A New Therapy Paradigm for Prostate Cancer Founded on Clinical Observations
Authors: Eleni Efstathiou, Christopher J. Logothetis
Journal: Clinical Cancer Research (2010)

Abstract Efficacy equivalent to that reported in other common adult solid tumors considered to be chemotherapy-sensitive has been reported with Docetaxel in patients with castrate-resistant prostate cancer. However, in contrast to other cancers, the expected increase in efficacy with the use of chemotherapy in earlier disease states has not been reported to date in prostate cancer. On the basis of these observations, we speculated that the therapy development paradigm used successfully in other cancers may not apply to the majority of prostate cancers. Several lines of supporting clinical and experimental observations implicate the tumor microenvironment in prostate carcinogenesis and resistance to therapy. We conclude that a foundation to guide the development of therapy for prostate cancer is required. The therapy paradigm we propose accounts for the central role of the tumor microenvironment in bone and, if correct, will lead to microenvironment-targeted therapy. Clin Cancer Res; 16(4); 1100–7
Significance of EGFR expression patterns in patients with non-small cell lung cancer – Evaluation on protein- and/or gene level?
Authors: Rania Gaber, Iris Watermann, Christian Kugler, Nils Reinmuth, Rudolf-Maria Huber, Philipp Schnabel, Ekkehard Vollmer, Martin Reck, Torsten Goldmann
Journal: European Respiratory Journal (2014)

Introduction:  Several EGFR-specific molecular inhibitors are currently used in clinical oncology. Thus, the determination of EGFR status on protein level as well as the detection of EGFR mutations to identify patients who show high response rates towards TKIs, is essential. Up to now, common EGFR evaluation criteria are still missing, but absolutely necessary.  Aims and objectives:  To identify enlarged collectives of patients who might benefit from Tyrosine kinase inhibitors, in addition to those bearing activating mutations, we wanted to figure out which is the optimized method of EGFR expression evaluation on protein level in addition to the determination of gene amplification status.  Methods:  206 tumor tissues were analyzed in a tissue microarray format employing immunohistochemistry (IHC) with four different antibodies including Dako PharmDx kit (clone 2-18C9), clone 31G7, clone 2.1E1 and clone SP84 using three different scoring methods. Protein expression was compared to fluorescence in situ hybridization (FISH) using two different probes. Data of IHC and FISH-analysis were further correlated with clinicopathological data to find out, whether IHC could be the method of choice, probably coupled to FISH-analysis.  Results:  Two different FISH probes revealed identical gene amplification status in NSCLC tumor samples. EGFR protein expression evaluated by IHC correlates significantly with FISH results; best correlation is shown for 31G7 using scoring method B.  Conclusion:  Our advice is to use Dako PharmDx, 31G7 or 2.1E1 in IHC and confirm these data by FISH analysis to facilitate more patients for EGFR specific treatments concerning their EGFR expression pattern.
Lab support for strong reciprocity is weak: Punishing for reputation rather than cooperation
Authors: Alex Shaw, Laurie Santos
Journal: Behavioral and Brain Sciences (2012)

Abstract Strong reciprocity is not the only account that can explain costly punishment in the lab; it can also be explained by reputation-based accounts. We discuss these two accounts and suggest what kinds of evidence would support the two different alternatives. We conclude that the current evidence favors a reputation-based account of costly punishment.
Dynamics of nasal eosinophils in response to a nonnatural allergen challenge in patients with allergic rhinitis and control subjects: A biopsy and brush study1
Authors: T GODTHELP, A HOLM, W FOKKENS, P DOORNENBAL, P MULDER, E HOEFSMIT, A KLEINJAN, E PRENS, E RIJNTJES
Journal: Journal of Allergy and Clinical Immunology (1996)
Exercise unmasks autonomic dysfunction in swine with a recent myocardial infarction
Authors: D DUNCKER, D HAITSMA, D LIEM, P VERDOUW, D MERKUS
Journal: Cardiovascular Research (2005)

Objective: Severe congestive heart failure is associated with autonomic imbalance consisting of an increased sympathetic and decreased parasympathetic activity. In the present study, we investigated the influence of alterations in autonomic balance on cardiovascular function in 11 swine with left ventricular (LV) dysfunction produced by a 2- to 3-week-old myocardial infarction (MI).
Case-control study of severe life threatening asthma (SLTA) in adults: psychological factors
Authors: J Kolbe
Journal: Thorax (2002)

Severe life threatening asthma (SLTA) is important in its own right and as a proxy for asthma death. In order to target hospital based intervention strategies to those most likely to benefit, risk factors for SLTA among those admitted to hospital need to be identified. Adverse psychological factors are purported risk factors for asthma death and SLTA /near fatal asthma. A study was undertaken to determine whether, in comparison with patients admitted to hospital with acute asthma, those with SLTA have specific adverse psychological factors.A case-control study was undertaken. Cases (n=77) were admitted to the intensive care unit with SLTA (mean (SD) pH 7.17 (0.15), PaCO(2) 10.7 (5.0) kPa). Controls (n=239) were admitted to general wards with acute asthma and were matched only by date of index attack. An interviewer administered questionnaire was undertaken 24-48 hours after admission. A random sample of community based asthmatics was recruited to provide normative data on asthmatics for comparison with cases and hospital controls.The risk of SLTA increased with age (OR 1.04/year, 95% CI 1.01 to 1.07) and was less for women (OR 0.36, 95% CI 0.20 to 0.68). These variables were controlled for in all further analyses. There was a high prevalence of psychological disorder in both cases and matched controls, but there was no difference in prevalence of caseness for anxiety or depression, total (or individual) life events in last 12 months, availability of general or disease specific social support, nor in any of the domains of the Attitudes and Beliefs about Asthma Questionnaire (emotional (mal) adjustment, doctor-patient relationship, stigma, self-efficacy). Cases (SLTA) were less likely to have had previous emotional counselling (25% v. 35%, p<0.05). However, when comparison was made with a community based group of asthmatic patients, those admitted to hospital with acute asthma (SLTA and hospital controls) had a higher prevalence of anxiety and depression, higher total life events, and higher prevalence of certain specific life events.There was considerable psychological morbidity generally (and anxiety specifically) in those admitted with acute asthma. Specific adverse psychological factors were not risk factors for SLTA, when comparison was made with those admitted to hospital with acute asthma, but adverse psychological factors were a risk factor for hospitalisation for acute asthma (including SLTA). Psychological risk factors for adverse events in asthma are dependent both on the type of event under study and the comparison group used.
EXPERIMENTAL STUDIES ON THE ADMINISTRATION OF SALVARSAN BY MOUTH TO ANIMALS AND MAN
Authors: John A. Kolmer, Jay Frank Schamberg
Journal: The Journal of Experimental Medicine (1912)

Salvarsan in capsule and in solution in doses varying from 0.1 to 0.6 of a gram was administered by mouth to seven patients suffering from syphilis. Five patients were given full doses of 0.6 of a gram. One patient (case 3) received in the aggregate within four weeks 2.4 grams without loss of weight or any disturbing effects. An ulcerating gumma of the knee was practically healed after a period of five weeks. This was the only patient of the seven, however, in whom notable improvement in the cutaneous manifestations followed the administration of the drug. This ulceration would probably have healed as soon, or possibly sooner, under the influence of mercury and the iodids. From the above observations, it would appear that salvarsan administered by mouth up to the full dose of 0.6 of a gram, has a perceptible though feeble therapeutic effect on cutaneous syphilitic manifestations. We should naturally expect the influence of any drug to be more evident in the case of a gumma, in which spirochaetes are only sparsely present, than in the secondary syphilides in which the spirochaetes are present in enormous numbers. Cutaneous gummata are readily healed at times by very small doses of mercury or iodids. It is interesting to note that the administration of the full dose of the drug by mouth does not appear to give rise to symptoms of systemic arsenical poisoning, unless the vomiting and diarrhea be regarded as such. After some of the full dose administrations, there was neither vomiting nor diarrhea. As salvarsan contains 34 per cent. of arsenic, these patients received the equivalent of five grains of arsenic. In case 3, in the course of four weeks the patient took by mouth the equivalent of over twelve grains of arsenic, without vomiting or having diarrhea, and with no loss of weight or disturbance of health. The urine of this patient was entirely normal. It would seem, therefore, that salvarsan is not converted in the gastro-intestinal tract into an organotropic arsenical compound, and it is possible that it may remain practically unchanged.
Comparison of visual and semiquantitative analysis of 18F-FDOPA-PET/CT for recurrence detection in glioblastoma patients
Authors: K. Herrmann, J. Czernin, T. Cloughesy, A. Lai, K. L. Pomykala, M. R. Benz, A. K. Buck, M. E. Phelps, W. Chen
Journal: Neuro-Oncology (2013)

Amino acid transport imaging with 18F-FDOPA PET is increasingly used for detection of glioblastoma recurrence. However, a standardized image interpretation for 18F-FDOPA brain PET studies has not yet been established. This study compares visual and semiquantitative analysis parameters for detection of tumor recurrence and correlates them with progression-free survival (PFS). One-hundred ten patients (72 male:38 female) with suspected tumor recurrence who underwent 18F-FDOPA PET imaging were studied. PET scans were analyzed visually (5-point scale) and semiquantitatively (lesion-to-striatum- and lesion- to-normal-brain-tissue ratios using both SUVmean and SUVmax). Accuracies for recurrence detection were calculated using histopathology and clinical follow-up for validation. Receiving operator characteristic and Kaplan-Meier survival analysis were performed to derive imaging-based prediction of PFS and overall survival (OS). Accuracies for detection of glioblastoma recurrence were similar for visual (82%) and semiquantitative (range, 77%–82%) analysis. Both visual and semiquantitative indices were significant predictors of PFS, with mean lesion-to normal brain tissue ratios providing the best discriminator (mean survival, 39.4 vs 9.3 months; P < .001). None of the investigated parameters was predictive for OS. Both visual and semiquantitative indices detected glioblastoma recurrence with high accuracy and were predictive for PFS. Lesion-to-normal-tissue ratios were the best discriminators of PFS; however, none of the investigated parameters predicted OS. These retrospectively established analysis parameters need to be confirmed prospectively.
Humoral factor that specifically regulates factor X levels in rabbits (coagulopoietin-X).
Authors: D Trauber, K Hawkins, M Karpatkin, S Karpatkin
Journal: Journal of Clinical Investigation (1979)

A heat-stable humoral substance (coagulopoietin-X) is present in rabbits partially depleted of Factor X, which is capable of raising Factor X levels when injected into recipient rabbits. Rabbits were partially depleted of Factor X by slow infusion of a globulin fraction of goat anti-rabbit Factor X antibody. This resulted in the reduction of Factor X to 40--50% of normal at 1 h and 60--70% of normal at 6 h. No effect was noted on levels of Factors II, V, or VII. Plasma from these animals, when injected into 10 recipients, specifically raised Factor X levels when measured by four different assay: one-stage assay with bovine VII- and X-deficient plasma and Russell's viper venom; one-stage assay with human X-deficient plasma and thromboplastin; chromogenic substrate assay with Russell's viper venom; and an immunologic assay (Laurell technique). No rise was noted in two control experiments in which normal plasma was injected into recipient rabbits from 2 rabbits injected with a globulin fraction of normal goat serum, nor in 12 rabbits injected with plasma from normal rabbits, nor in 5 rabbits injected with boiled plasma from normal rabbits. The rise in biologic activity of 120--150% of base line was significantly greater than the rise in immunologic activity of 114--117% of base line (P less than 0.05) on 3 different days, suggesting the production of a molecule with greater specific activity rather than increased protein synthesis.
Oxidative phosphorylation and aspects of calcium metabolism in myocardia of hypercholesterolaemic swine with moderate coronary atherosclerosis
Authors: E. S. MORRISON, R. F. SCOTT, W. M. LEE, J. FRICK, M. KROMS, C. P. CHENEY
Journal: Cardiovascular Research (1977)

Aspects of myocardial oxidative phosphorylation and Ca2+ metabolism were studied in a swine model in which coronary atherosclerosis was induced by a combination of denudation of the endothelium of the coronary arteries plus 7-11 months of feeding a high fat-high cholesterol diet. By microscopy, a moderate amount of coronary atherosclerosis was present at the time of sacrifice, and 2 of the 14 swine hearts had old myocardial infarcts. Myocardial mitochondria from grossly normal areas showed partial uncoupling and decreased state 3 O2 uptake with 3 of 4 substrates tested. In addition, Ca2+ stimulated mitochondrial respiration was decreased in the atherosclerotic swine. In the sarcoplasmic reticulum Ca2+ uptake under conditions of heavy loading was greater in the atherosclerotic swine than in control animals. The degree of atherosclerosis was not great enough to suggest that persistent myocardial ischaemia was present. Possibly coronary artery spasm induced an intermittent ischaemia resulting in the metabolic abnormalities observed, or the changes may have been brought about by the effects of the high fat-high cholesterol diet on subcellular membranes.
Resting heart rate is a predictor of mortality in COPD
Authors: Magnus Thorsten Jensen, Jacob L. Marott, Peter Lange, Jørgen Vestbo, Peter Schnohr, Olav Wendelboe Nielsen, Jan Skov Jensen, Gorm B. Jensen
Journal: European Respiratory Journal (2012)

The clinical significance of high heart rate in chronic obstructive pulmonary disease (COPD) is unexplored. We investigated the association between resting heart rate, pulmonary function, and prognosis in subjects with COPD. 16 696 subjects aged ≥40 years from the Copenhagen City Heart Study, a prospective study of the general population, were followed for 35.3 years, 10 986 deaths occurred. Analyses were performed using time-dependent Cox-models and net reclassification index (NRI). Resting heart rate increased with severity of COPD (p<0.001). Resting heart rate was associated with both cardiovascular and all-cause mortality across all stages of COPD (p<0.001). Within each stage of COPD, resting heart rate improved prediction of median life expectancy; the difference between <65 bpm and >85 bpm was 5.5 years without COPD, 9.8 years in mild (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I), 6.7 years in moderate (GOLD stage II) and 5.9 years in severe/very severe COPD (GOLD stage III/IV), (p<0.001). Resting heart rate significantly improved risk prediction when added to GOLD stage (categorical NRI 4.9%, p = 0.01; category less NRI 23.0%, p<0.0001) or forced expiratory volume in 1 s % predicted (categorical NRI 7.8%, p = 0.002; category less NRI 24.1%, p<0.0001). Resting heart rate increases with severity of COPD. Resting heart rate is a readily available clinical variable that improves risk prediction in patients with COPD above and beyond that of pulmonary function alone. Resting heart rate may be a potential target for intervention in COPD.
Reduced Forms of Aminopterin and Methotrexate in L1210 Lymphoma 2
Authors: David R. Makulu, Eckard Fölsch
Journal: JNCI Journal of the National Cancer Institute (1977)

We examined several characteristics of reduced forms of folate antagonists. Dihydro and tetrahydro derivatives of aminopterin and methotrexate (MTX) were chemically prepared. When titrated with dihydrofolate reductase, reduced derivatives were equipotent with the parent compounds and titrated stoichiometrically with the enzyme at pH 6 and nonstoichiometrically at higher pH conditions (pH 7.4 and above). When incubated with L1210 cells in vitro, rates of uptake of tritiated reduced compounds were significantly less in L1210 and L1210/MTX cells compared with the respective oxidized parent compounds and significantly less in L1210/MTX than in L1210 cells. Although dihydroaminopterin and tetrahydromethotrexate increased the survival rate of mice bearing L1210 tumors, these compounds had no such effect on the life-spans of animals with L1210/MTX tumor.
Differential Expression of MicroRNAs in Different Disease States
Authors: Maha Abdellatif
Journal: Circulation Research (2012)

Disturbances in gene expression as a result of perturbed transcription or posttranscriptional regulation is one of the main causes of cellular dysfunction that underlies different disease states. Approximately a decade ago, the discovery of microRNAs in mammalian cells has renewed our focus on posttranscriptional regulatory mechanisms during pathogenesis. These tiny posttranscriptional regulators are differentially expressed in almost every disease that has been studied to date and can modulate expression of a gene via specifically binding to its messenger RNA. Because of their capacity to simultaneously target multiple functionally related, genes, they are proving to be potentially powerful therapeutic agents/targets. In this review, we focus on the microRNAs that are differentially regulated in the more common cardiovascular pathologies, their targets, and potential function.
Colonic Cancer in Ulcerative Colitis and Idiopathic Colonic Cancer
Authors: Claude E. Welch
Journal: JAMA (1965)

Carcinomas of the colon and rectum that develop in patients with chronic ulcerative colitis (CUC) are believed to differ in several ways from those that are observed in the general population (hereafter known as normals). Generally, they are considered to be more common, to develop more frequently in the proximal colon, to occur in younger patients, and to carry a graver prognosis. In this paper, the evidence supporting these conclusions will be considered. Data will be drawn from a study of the 750 patients with CUC who entered the Massachusetts General Hospital from 1943 to 1962. At the outset, it is well to outline some of the differences involved in any statistical study of this type. In the first place, the population of patients with CUC cannot be defined exactly because of inaccuracies in diagnosis among hospitalized patients as well as the fact that an indefinite number of patients do
A COMPARATIVE STUDY OF RECENTLY ISOLATED HUMAN STRAINS AND A PASSAGE STRAIN OF POLIOMYELITIS VIRUS
Authors: John R. Paul, James D. Trask
Journal: The Journal of Experimental Medicine (1933)

1. Confirmation of the qualitative differences which exist between so called human and passage strains of poliomyelitis virus has been established by the following observations. (a) The experimental disease induced by two human strains usually failed to protect monkeys against a subsequent infection by a passage strain, and in the few instances in which the reverse experiment could be tried a similar lack of protection was observed. (b) In some human sera the neutralizing power for a human strain differed qualitatively from the neutralizing power for a passage strain. 2. The time interval between the intracerebral inoculation of heterologous strains has been found to be an important factor bearing upon the results of the reinoculation experiments reported. Within the intervals used, the greater the period between the original infection and the reinoculation with a heterologous strain, the less was the degree of cross-immunity observed.
Detection of SV40 like viral DNA and viral antigens in malignant pleural mesothelioma
Authors: M Ramael, J Nagels, H Heylen, S De Schepper, J Paulussen, M De Maeyer, C Van Haesendonck
Journal: European Respiratory Journal (1999)

This study investigated the presence of simian vacuolating virus 40 (SV40) deoxyribonucleic acid (DNA) in malignant pleural mesothelioma, non-neoplastic mesothelium and pleural carcinoma metastasis and correlated these data with immunohistochemistry for SV40 viral antigens. The novel Primed In Situ (PRINS) method was applied to detect the presence of SV40 DNA in situ in tissue sections of malignant mesothelioma (n = 25), non-neoplastic mesothelium (n = 30) and pleural carcinoma metastasis (n = 30). Immunohistochemistry with an SV40-specific antibody was applied for detection of the SV40 viral antigen in the same material. SV40 DNA and expression of one of the viral proteins (small t-antigen) was found in approximately 60% of the investigated mesothelioma cases in contrast to non-neoplastic mesothelium and carcinoma metastasis that were negative for both SV40 DNA and SV40 viral antigens. These results suggest that simian vacuolating virus 40 deoxyribonucleic acid may be biologically active as there was also immunoreactivity for simian vacuolating virus 40 viral antigen in those cases positive for simian vacuolating virus 40 deoxyribonucleic acid with the primed in situ reaction. Simian vacuolating virus 40 viral deoxyribonucleic acid and antigens may be potential markers for neoplastic mesothelium that may prove useful in the rather difficult histopathological differential diagnosis between malignant mesothelioma and reactive mesothelium or pleural carcinoma.