tbuckley/cabot-search huggingface dataset:
The myocardial energetic active state. I. Oxygen consumption during tetanus of cat papillary muscle.
Authors: G Cooper
Journal: Circulation Research (1976)

The potential role of active state maintenance as a determinant of myocardial oxygen consumption (MVO2) has not been defined. Right ventricular papillary muscles from 15 cats were studied in a polarographic myograph at 23 degrees C in a Krebs-Ringer solution containing 7.5 mM Ca2+ and 10 mM caffeine. MVO2 was determined for isometric tetani at Lmax of 1-5 seconds' duration. Increases in tetanus duration related linearly to increments in both active tension time (delta active tension) and MVO2. In order to examine the oxygen cost of active state maintenance not attributable to associated tension generation, both the same isometric and 2.5- to 10.0-second lightly preloaded isotonic tetani were produced in nine muscles. For each tetanus duration the contribution throughout the contraction of developed force (preload) to MVO2 could be subtracted from overall isotonic MV02. In the absence of the MVO2 associated with force development, the active state duration was related linearly to MVO2, with a mean active state MVO2 of 2.42 +/- 0.29 nl O2/mg dry muscle/sec of isotonic tetanus; this MVO2 is 68% of the value of 3.58 +/- 0.42 nl O2/mg dry muscle/sec that was obtained for isometric tetanus at Lmax. This study identifies active state maintenance as the major determinant of MVO2 during myocardial tetanus and, furthermore, suggests the possibility that alterations in ative state intensity and duration may be the biochemical mechanism by which other determinants of MVO2 act in a more physiological setting.
Treatment of bone loss in osteopenic patients with Crohn's disease: a double-blind, randomised trial of oral risedronate 35 mg once weekly or placebo, concomitant with calcium and vitamin D supplementation
Authors: Ad A van Bodegraven, Nathalie Bravenboer, Birgit I Witte, Gerard Dijkstra, C Janneke van der Woude, Pieter C M Stokkers, Maurice G Russel, Bas Oldenburg, Marieke Pierik, Jan C Roos, Ruud A van Hogezand, Vincent K Dik, Angela E Oostlander, J Coen Netelenbos, Lex van de Langerijt, Daniel W Hommes, Paul Lips
Journal: Gut (2013)

<h3>Abstract</h3> Biological sex affects numerous aspects of biology, yet how sex influences different biological processes has not been extensively studied at the molecular level. <i>Caenorhabditis elegans</i>, with both hermaphrodites (functionally females as adults) and males, is an excellent system to uncover how sex influences physiology. Here, we describe a method to isolate large quantities of <i>C. elegans</i> males by conditionally degrading DPY-27, a component of the dosage compensation complex essential for hermaphrodite, but not male, development. We show that germ cells from males isolated following DPY-27 degradation undergo meiosis and spermiogenesis like wild type and are competent to mate and produce viable offspring. We demonstrate the efficacy of this system by analyzing gene expression and performing affinity pull-downs from male worm extracts.
Induction of Simian Virus 40 (SV40) Transplantation Immunity in Mice by SV40-Transformed Cells of Various Species
Authors: Lloyd W. Law, Kenneth K. Takemoto, Michael J. Rogers, Robert C. Ting
Journal: JNCI Journal of the National Cancer Institute (1977)

Specific tumor rejection was obtained with the use of simian virus 40 (SV40)-transformed cells from several species including man, rat, ape, sheep, and hamster. Growth of the syngeneic sarcoma mKSA in BALB/c mice was strikingly inhibited following a single immunization with as few as 10(3) intact, viable cells. Non-SV40-transformed cells did not induce tumor rejection activity nor did SV40-transformed lines induce immunity against the 3-methylcholanthrene-induced sarcoma Meth A, syngeneic with BALB/c mice. A close relationship existed between the tumor rejection antigen, the tumor-specific transplantation antigen (TSTA) located on the plasma membrane, and the intranuclear tumor antigen (T-ag). Both were associated with the DNA sequence of the early region of the SV40 genome, and TSTA activity was found in the nucleus. However, we did not observe a close parallelism between T-ag activity and TSTA. Neverthesless, the results strongly suggested that TSTA, like T-ag, was encoded by the virus.
Robert Koch: centenary of the discovery of the tubercle bacillus, 1882.
Authors: A Sakula
Journal: Thorax (1982)

This is an account of the life and work of Robert Koch (1843-1910), Nobel Laureate in Medicine and a founder of the science of bacteriology. In particular, Koch9s researches into tuberculosis are described--the discovery of the tubercle bacillus, the controversy regarding the human and bovine types, the Koch phenomenon, and the introduction of tuberculin, which proved to be ineffective as a cure but became important as a diagnostic tool in the management of tuberculosis. By his achievements in this field, Koch may be considered to be the father of the scientific study of tuberculosis. On the occasion of the centenary of Koch9s discovery of the tubercle bacillus in 1882, we pay tribute to this great German master of medicine.
Front-line treatment of metastatic breast cancer with docetaxel and epirubicin: A multicenter dose-escalation study
Authors: C. Kouroussis, E. Xydakis, A. Potamianou, T. Giannakakis, S. Kakolyris, S. Agelaki, E. Sara, N. Malamos, A. Alexopoulos, D. Mavroudis, G. Samonis, S. Papadouris, V. Georgoulias, G. Panagos
Journal: Annals of Oncology (1999)

To determine the maximum tolerable dose (MTD) and the dose-limiting toxicity (DLT) of docetaxel (D) in combination with epirubicin (Epi) in patients with advanced breast cancer.Forty-seven chemotherapy-naïve metastatic breast cancer patients aged < 75 years with PS (WHO) 0-2 and adequate bone marrow, renal, liver and cardiac function, were enrolled in the study. Epi was given as a five-min bolus i.v. infusion on day 1 (d1) in escalated doses with increments of 10 mg/m2; D was given in a one-hour infusion after appropriate premedication on either day 1 or on day 2 in escalated doses with increments of 10 mg/m2. The patients' median age was 60 years, 42 (89%) had a PS (WHO) 0-1, 16 (34%) were premenopausal and 25 (53%) had visceral disease.When the two drugs were given on the same day, the MTD1 was reached at the doses of Epi 60 mg/m2 and D 80 mg/m2; administration of G-CSF could not result in a dose intensification. When the drugs were given on two consecutive days, the MTD2 was reached at the doses of Epi 80 mg/m2 (d1) and D 90 mg/m2 (d2). The dose-limiting events were febrile neutropenia and grade 4 neutropenia, which developed in 30 (64%) patients during the study; among 227 delivered cycles grade 3-4 neutropenia occurred in 64 (28%) cycles but only 22 (10%) of them were complicated by fever. There were no septic deaths. Grade 1-2 neurosensory toxicity occurred in nine (19%) patients, mild edema in eight (17%) and allergic reactions in five (11%). Four (9%) patients presented a greater than 10% decrease of LVEF and treatment discontinuation was required in two of them; none of the patients developed congestive heart failure. Nevertheless, one patient suddenly died 10 days after treatment initiation of myocardial ischemia, and this death is considered treatment-related. Five (14.7%) complete and thirteen (38.2%) partial responses (ORR: 53.9%; 95% confidence interval: 36.1%-69.7%) were observed in 34 evaluable patients. Ten (29.4%) and six (17.6%) patients had stable and progressive disease, respectively. The median duration of response and time to tumor progression were five and seven months, respectively. The median survival has not yet been reached.The combination of epirubicin and docetaxel is a feasible and well tolerated regimen, but the MTD depends on the administration schedule of the drugs.
Hepatocellular uptake of sulfobromophthalein and bilirubin is selectively inhibited by an antibody to the liver plasma membrane sulfobromophthalein/bilirubin binding protein.
Authors: W Stremmel, P D Berk
Journal: Journal of Clinical Investigation (1986)

To clarify sulfobromophthalein (BSP) and bilirubin uptake mechanisms, isolated rat hepatocytes were incubated with [35S]BSP. The initial uptake velocity (V0), determined from the first, linear portion of the cumulative uptake curve, was saturable (Michaelis constant [Km] = 6.2 +/- 0.5 microM; Vmax = 638 +/- 33 pmol X min-1 per 10(5) hepatocytes), maximal at 37 degrees C and pH 7.4, and competitively inhibited by bilirubin, but not by taurocholate, cholate, or oleate. Preloading with unlabeled BSP led to trans-stimulation of V0. Sodium substitution or pretreatment of hepatocytes with ouabain or metabolic inhibitors had no effect on V0; trypsin reduced V0 by 39% (P less than 0.001). A rabbit antiserum to the rat liver plasma membrane (LPM)-BSP/bilirubin binding protein selectively reduced V0 of 5 microM [35S]BSP and [14C]bilirubin by 41 and 42%, respectively (P less than 0.01); uptakes of [3H]oleate, [3H]cholate and [3H]taurocholate were not affected. Hence, the LPM-BSP/bilirubin binding protein plays a role in the carrier-mediated uptake of BSP and bilirubin by hepatocytes.
The Continuous Erythropoietin Receptor Activator Affects Different Pathways of Diabetic Renal Injury
Authors: Jan Menne, Joon-Keun Park, Nelli Shushakova, Michael Mengel, Matthias Meier, Danilo Fliser
Journal: Journal of the American Society of Nephrology (2007)

This study explored the tissue-protective properties of the continuous erythropoietin receptor activator (CERA) in an experimental model of (nonischemic) diabetic kidney injury (i.e., the db/db mouse). Mice were randomly treated with placebo (n = 25), low-dosage CERA (n = 25), and high-dosage CERA (n = 25). Also studied were 25 nondiabetic db/m mice. Hematocrit was comparable in placebo and low-dosage CERA-treated mice but increased significantly with high-dosage CERA (P < 0.01 versus both). Significantly reduced expression of TGF-beta, vascular endothelial growth factor, and collagen IV was found in glomeruli and the tubulointerstitial area with CERA treatment, and these beneficial molecular effects were clearly dosage dependent (both P < 0.05 versus placebo). Similarly, CERA treatment caused a dosage-dependent increase in p-Akt, nephrin, and perlecan tissue expression (all P < 0.05 versus placebo). However, the accelerated mesangial expansion that was observed in placebo-treated db/db mice (versus db/m controls) was significantly reduced only in low-dosage CERA-treated mice (P < 0.01). Moreover, albuminuria was significantly reduced in low- but not high-dosage CERA-treated mice compared with placebo treatment (P < 0.05). In an ancillary study, phlebotomy was performed in high-dosage CERA-treated db/db mice to keep hematocrit within normal (baseline) levels. This procedure resulted in significantly (P < 0.05) less albuminuria as compared with high-dosage CERA-treated mice without phlebotomy, thus preserving the tissue-protective potential of CERA. Long-term CERA treatment has beneficial dosage-dependent effects on molecular pathways of diabetic kidney damage. Low-dosage CERA does not affect hematocrit and therefore may be a feasible method of tissue protection in this setting.
St. Mary's Hospital. CASES OF LICHEN AND PRURIGO: WITH REMARKS
Authors: C. H. Jones
Journal: BMJ (1855)

k h w bemme naly quite powerless, and h am h ly Complains of t ead e; speech way dilcult and indistinct.No afection of the sight, no n.peeived in the ear Appetite very bad from the ning.The only cause for the appearanee of the above Vtoma was rheumatic fever, which she suffered from for roo weeks just before the chorea appeared.Never no- heed any worms in excrements.On the 25th, she began taking one grain of oxide of zinc morning and evening; but, on the 28th, no improvement
Presence of the Carcinogen <i>N</i>′-Nitrosonornicotine in the Urine of Some Users of Oral Nicotine Replacement Therapy Products
Authors: Irina Stepanov, Steven G. Carmella, Anna Briggs, Louise Hertsgaard, Bruce Lindgren, Dorothy Hatsukami, Stephen S. Hecht
Journal: Cancer Research (2009)

N'-nitrosonornicotine (NNN) is a strong carcinogen present in unburned tobacco and cigarette smoke. We here analyze data obtained in two studies, in which a biomarker of exposure to NNN--the sum of NNN and its pyridine-N-glucuronide, called total NNN--was quantified in the urine of people who had stopped smoking and used various nicotine replacement therapy (NRT) products. In 13 of 34 nicotine gum or lozenge users from both studies, total NNN at one or more time points after biochemically confirmed smoking cessation was comparable with, or considerably higher than, the baseline levels. For most of the subjects who used the nicotine patch as a smoking cessation aid, urinary total NNN at all post-quit time points was <37% of their mean baseline levels. These results indicate that endogenous formation of significant amounts of NNN may occur sporadically in some users of oral NRT. Given the carcinogenicity of NNN and the frequent use of nicotine gum as a smoking cessation aid, further studies are needed so that preventive measures can be developed.
A large chest wall tumour in an asymptomatic 15-year-old girl
Authors: K-C Chen, W-C Lin, Y-C Lee, J-S Chen, H-H Hsu
Journal: Thorax (2007)

A 15-year-old girl that had plain chest x ray as part of a routine medical examination was found to have a large left lower chest wall mass associated with rib destruction that was later shown to …
HUMAN FLAVIN-CONTAINING MONOOXYGENASES
Authors: John R. Cashman, Jun Zhang
Journal: The Annual Review of Pharmacology and Toxicology (2006)

This review summarizes recent information concerning the pharmacological and toxicological significance of the human flavin-containing monooxygenase (FMO, EC 1.14.13.8). The human FMO oxygenates nucleophilic heteroatom-containing chemicals and drugs and generally converts them into harmless, polar, readily excreted metabolites. Sometimes, however, FMO bioactivates chemicals into reactive materials that can cause toxicity. Most of the interindividual differences of FMO are due to genetic variability and allelic variation, and splicing variants may contribute to interindividual and interethnic variability observed for FMO-mediated metabolism. In contrast to cytochrome P450 (CYP), FMO is not easily induced nor readily inhibited, and potential adverse drug-drug interactions are minimized for drugs prominently metabolized by FMO. These properties may provide advantages in drug design and discovery, and by incorporating FMO detoxication pathways into drug candidates, more drug-like materials may be forthcoming. Although exhaustive examples are not available, physiological factors can influence FMO function, and this may have implications for the clinical significance of FMO and a role in human disease.
<i>HMGA2</i> Overexpression-Induced Ovarian Surface Epithelial Transformation Is Mediated Through Regulation of EMT Genes
Authors: Jingjing Wu, Zhaojian Liu, Changshun Shao, Yaoqin Gong, Eva Hernando, Peng Lee, Masashi Narita, William Muller, Jinsong Liu, Jian-Jun Wei
Journal: Cancer Research (2011)

The AT-hook transcription factor HMGA2 is an oncogene involved in the tumorigenesis of many malignant neoplasms. HMGA2 overexpression is common in both early and late-stage high-grade ovarian serous papillary carcinoma. To test whether HMGA2 participates in the initiation of ovarian cancer and promotion of aggressive tumor growth, we examined the oncogenic properties of HMGA2 in ovarian surface epithelial (OSE) cell lines. We found that introduction of HMGA2 overexpression was sufficient to induce OSE transformation in vitro. HMGA2-mediated OSE transformation resulted in tumor formation in the xenografts of nude mice. By silencing HMGA2 in HMGA2-overexpressing OSE and ovarian cancer cell lines, the aggressiveness of tumor cell growth behaviors was partially suppressed. Global gene profiling analyses revealed that HMGA2-mediated tumorigenesis was associated with expression changes of target genes and microRNAs that are involved in epithelial-to-mesenchymal transition (EMT). Lumican, a tumor suppressor that inhibits EMT, was found to be transcriptionally repressed by HMGA2 and was frequently lost in human high-grade serous papillary carcinoma. Our findings show that HMGA2 overexpression confers a powerful oncogenic signal in ovarian cancers through the modulation of EMT genes.
ATF6β is a host cellular target of the <i>Toxoplasma gondii</i> virulence factor ROP18
Authors: Masahiro Yamamoto, Ji Su Ma, Christina Mueller, Naganori Kamiyama, Hiroyuki Saiga, Emi Kubo, Taishi Kimura, Toru Okamoto, Megumi Okuyama, Hisako Kayama, Kisaburo Nagamune, Seiji Takashima, Yoshiharu Matsuura, Dominique Soldati-Favre, Kiyoshi Takeda
Journal: The Journal of Experimental Medicine (2011)

The ROP18 kinase has been identified as a key virulence determinant conferring a high mortality phenotype characteristic of type I Toxoplasma gondii strains. This major effector molecule is secreted by the rhoptries into the host cells during invasion; however, the molecular mechanisms by which this kinase exerts its pathogenic action remain poorly understood. In this study, we show that ROP18 targets the host endoplasmic reticulum-bound transcription factor ATF6β. Disruption of the ROP18 gene severely impairs acute toxoplasmosis by the type I RH strain. Because another virulence factor ROP16 kinase modulates immune responses through its N-terminal portion, we focus on the role of the N terminus of ROP18 in the subversion of host cellular functions. The N-terminal extension of ROP18 contributes to ATF6β-dependent pathogenicity by interacting with ATF6β and destabilizing it. The kinase activity of ROP18 is essential for proteasome-dependent degradation of ATF6β and for parasite virulence. Consistent with a key role for ATF6β in resistance against this intracellular pathogen, ATF6β-deficient mice exhibit a high susceptibility to infection by ROP18-deficient parasites. The results reveal that interference with ATF6β-dependent immune responses is a novel pathogenic mechanism induced by ROP18.
<i>Tropheryma whippelii</i> DNA Is Rare in the Intestinal Mucosa of Patients without Other Evidence of Whipple Disease
Authors: Matthias Maiwald, Axel von Herbay, David H. Persing, P. Shawn Mitchell, Manal F. Abdelmalek, Jill N. Thorvilson, David N. Fredricks, David A. Relman
Journal: Annals of Internal Medicine (2001)

Background: Little is known about the pathogenesis of Whipple disease, the reservoirs of Tropheryma whippelii, and the proportion of persons harboring the bacterium without "classic" intestinal abnormalities. Objective: To assess the presence of T. whippelii in patients undergoing upper endoscopy for a variety of indications. Design: Prospective and routine diagnostic examination of patients. Setting: Three academic medical centers in California; Minnesota; and Heidelberg, Germany. Patients: 342 patients undergoing endoscopy for evaluation of dyspepsia or possible peptic ulcer (group A, 173 patients), malabsorption (group B, 37 patients), or clinical suspicion of Whipple disease (group C, 132 patients). Measurements: Small-intestinal biopsy specimens were tested by polymerase chain reaction for T. whippelii DNA and examined for histopathologic abnormalities. Results: All patients with negative histologic findings also had negative results for T. whippelii DNA. Conclusions: T. whippelii occurs only rarely in intestinal mucosa that lacks histopathologic evidence of Whipple disease. The human small intestinal mucosa is an unlikely reservoir for this organism.
To see or not to see, that is the question: Designing experiments to test perspective-taking in nonhumans
Authors: Irene M. Pepperberg
Journal: Behavioral and Brain Sciences (1998)

Heyes argues that we need alternative experiments to study those animal abilities generally considered to involve “theory of mind.” The studies she proposes, however, have as many problems as those that she criticizes. Further interactions should exist among researchers examining these capacities before additional experiments are undertaken.
A robust translational model of acute exacerbations in the tobacco-smoke and poly IC treated mouse
Authors: Vincent Russell, Paul Woodman, Andrew Connolly, Dianne Spicer, Joanna Dlugozima, Alan Young
Journal: European Respiratory Journal (2012)

Exposure to tobacco smoke (TS) for 4 days induces steroid-insensitive lung inflammation in mice. The effect of adding the viral mimetic poly IC (PIC) to TS-exposed mice was examined.

Methods . Mice were exposed daily to either TS or air for 4d. Saline or PIC was administered intra-nasally. The time course of lung inflammation was examined 4-120hrs after the last exposure and cell numbers measured in the BAL fluid. The acute effects of oral Dexamethasone (DEX 0.3mg/kg) or Roflumilast (ROF 5mg/kg) on the peak inflammation were examined. The effects of DEX on the kinetics of the enhanced inflammation were also examined.

Results TS caused a lung inflammation which was inhibited by ROF but not by DEX. PIC alone induced an inflammation that was not inhibited by DEX or ROF. Dosing PIC in addition to TS induced an exaggerated response that was significantly greater than the additive effect of the two stimuli. The enhanced response peaked 24hrs after the last exposure then slowly declined. Neutrophils were predominant over the first 48 hrs. Macrophage numbers increased at 24-72hrs and lymphocyte numbers peaked at 48-72hrs. The peak inflammation after TS/PIC exposure was significantly inhibited by ROF (53%, p<0.05) and DEX (56%, p<0.05), in contrast to the lack of efficacy of DEX against TS or PIC alone. A single dose of DEX after the last exposure reduced the exaggerated response over the entire 120hr study period, but did not fully resolve the inflammation.

Conclusions TS exposure for 4 days induced a steroid-insensitive lung inflammation. Addition of PIC markedly enhanced the inflammatory response which was sensitive to both steroids and roflumilast, mimicking features of human COPD.
HuEP5C7 as a Humanized Monoclonal Anti-E/P-Selectin Neurovascular Protective Strategy in a Blinded Placebo-Controlled Trial of Nonhuman Primate Stroke
Authors: J. Mocco, Tanvir Choudhri, Judy Huang, Elisabeth Harfeldt, Lyubov Efros, Corine Klingbeil, Vladimir Vexler, William Hall, Yuan Zhang, William Mack, Sulli Popilskis, David J. Pinsky, E. Sander Connolly
Journal: Circulation Research (2002)

Although inhibiting interaction of beta(2) integrins with cognate immunoglobulin class adhesion receptor ligands is an effective neuroprotective strategy in small mammal models of stroke, the strategy has failed in human trials. A completely different antiadhesion receptor strategy was therefore rigorously tested in a model that may more closely approximate human reperfused stroke. Early leukoadhesive events in postischemic cerebral microvessels are mediated by upregulated selectin-class adhesion receptors on endothelial cells. Therefore, a blocking antibody prepared against common P- and E-selectin epitopes was humanized to suppress complement activation and tested in a reperfused hemispheric stroke model in Papio anubis (baboon). Histological examination of postischemic cerebral microvessels revealed a strong upregulation of E-and P-selectin expression. Placebo-blinded administration of the humanized anti-human E- and P-selectin monoclonal antibody (HuEP5C7, 20 mg/kg IV, n=9; placebo, n=9) immediately after the onset of 1 hour of temporary ischemia resulted in trends showing reduced polymorphonuclear leukocyte (PMN) infiltration into ischemic cortex, reduced infarct volumes (by 41%), improved neurological score (by 35%), and improved ability to self-care (by 39%). Importantly, there was no evidence of systemic complement activation, immune suppression, or pathological coagulopathy associated with this therapy. These data suggest that a humanized anti-E/P-selectin antibody approach is safe and may be effective as a clinical treatment for human stroke.