tbuckley/cabot-search huggingface dataset:
Vitamin A deficiency potentiates carbon tetrachloride-induced liver fibrosis in rats
Authors: Wilfried F. Seifert, Anne Bosma, Adriaan Brouwer, Henk F. J. Hendriks, Paul J. M. Roholl, Rick E. W. van Leeuwen, Christa G.F. van Thiel-De Ruiter, Ingrid Seifert-Bock, Dick L. Knook
Journal: Hepatology (1994)

Earlier studies have shown that retinoid administration suppresses the generation of hepatic fibrosis and stimulates its regression in normal (i.e., vitamin A-sufficient) carbon tetrachloride-treated rats. This study focuses on the possible role of a marginal or deficient vitamin A status on carbon tetrachloride-induced fibrosis. This experimental study in rats shows that vitamin A status, reflected by hepatic retinoid content (retinol and retinyl esters), modulates the development of hepatic fibrosis induced by carbon tetrachloride. In rats with low hepatic retinoid levels (12 ± 0.9 μg/gm liver), carbon tetrachloride-induced liver fibrosis was more pronounced than in rats with sufficient hepatic retinoid levels (1,065 ± 327 μg/gm liver). Enhanced liver fibrogenesis was confirmed both morphologically and by a higher hydroxyproline content of the liver. It was associated with a reduced liver weight and the development of parenchymal regeneration nodules. Furthermore, carbon tetrachloride treatment itself reduced the hepatic retinoid content in rats independently of the liver vitamin A status before treatment and increased serum retinol levels in vitamin A-sufficient rats. The results show that the vitamin A status of the liver plays an important role in hepatic fibrogenesis. Low hepatic vitamin A levels, which can be the result not only of low dietary intake but also of interference with vitamin A metabolism by agents such as ethanol and carbon tetrachloride, may be a risk factor for the development of liver fibrosis. We suggest that retinoids modulate collagen synthesis and deposition irrespective of the degree of hepatocellular necrosis induced by carbon tetrachloride. The reduction of retinoid levels in fat-storing cells and fibroblast-like cells by an enhanced secretion of retinol from the liver into the circulation during carbon tetrachloride treatment may stimulate the transformation of these cells to fibroblasts and, in this way, contribute to fibrogenesis of the liver. (Hepatology 1994;19:193-201).
Oncolytic HSV Armed with Platelet Factor 4, an Antiangiogenic Agent, Shows Enhanced Efficacy
Authors: Ta-Chiang Liu, Tingguo Zhang, Hiroshi Fukuhara, Toshihiko Kuroda, Tomoki Todo, Robert L. Martuza, Samuel D. Rabkin, Andreas Kurtz
Journal: Molecular Therapy (2006)

Oncolytic herpes simplex viruses (HSV) have emerged as a promising platform for cancer therapy. However, efficacy as single agents has thus far been unsatisfactory. Tumor vasculature is critical in supporting tumor growth, but successful antiangiogenic approaches often require maintaining constant levels of antiangiogenic products. We hypothesized that oncolytic HSV has the potential to destroy tumor vasculature and that this effect can be enhanced by combination with antiangiogenic gene transfer. We examined the strategy of arming oncolytic HSV with an antiangiogenic transgene, platelet factor 4 (PF4). The PF4 transgene was inserted into oncolytic HSV G47Δ utilizing a bacterial artificial chromosome construction system. Whereas bG47Δ-empty showed robust cell killing and migration inhibition of proliferating endothelial cells (HUVEC and Py-4-1), the effect was further enhanced by PF4 expression. Importantly, enhanced potency did not impede viral replication. In vivo, bG47Δ-PF4 was more efficacious than its nonexpressing parent bG47Δ-empty at inhibiting tumor growth and angiogenesis in both human U87 glioma and mouse 37-3-18-4 malignant peripheral nerve sheath tumor models. Enhancing the antiangiogenic properties of oncolytic HSV through the expression of antiangiogenic factors such as PF4 is a powerful new strategy that targets both the tumor cells and tumor vasculature.
Antithrombin III Assays
Authors: Robert H. Yue
Journal: JAMA (1979)

<h3>To the Editor.—</h3> In a letter to the editor, Roger L. Bick, MD (239:296, 1978), commented on the clinical determination of antithrombin III, pointing out the usefulness of chromogenic substrate and that an increased predisposition to thromboembolic phenomena is associated with a decreased antithrombin III level. In reply, Harry L. Messmore, MD, and Jawed Fareed, PhD (240:345, 1978), questioned the use of autolytic forms of thrombin and the chromogenic substrate in the antithrombin III assay. The methods employed for antithrombin III assay can be roughly classified into two categories: immunological and functional. There are two types of functional assays available: the rate determination procedure and the end-point analysis. The rate of the inhibition of thrombin by antithrombin III depends on (1) the amount of antithrombin III present, (2) the amount of heparin or heparin-like substance present in the sample, and (3) the quantity of thrombin employed. It was first pointed
Metabolism of cysteinyl leukotrienes in the perfused rat liver: The influence of endotoxin pretreatment and the cellular hydration state
Authors: Matthias Wettstein, Birgitta Noé, Dieter Häussinger
Journal: Hepatology (1995)

The influence of endotoxin on the hepatic metabolism and elimination of 3H-leukotriene C4 (LTC4) and 3H-leukotriene E4 was studied in the single-pass perfused rat liver. Endotoxin (4 mg/kg body mass) was injected intraperitoneally 8 to 10 hours before livers were isolated for perfusion. Tritiated leukotriene C4 and leukotriene E4 (10 nmol/L) were infused for 5 minutes, and metabolites in bile were determined by high-pressure liquid chromatography. In livers without endotoxin pretreatment, single-pass uptake of LTC4 was 77.3% +/- 3.2%, and 73.8% +/- 1.8% of the radioactivity taken up was excreted into the bile within 80 minutes. In endotoxin-pretreated livers, LTC4 uptake was 62.8% +/- 3.5% and only 31.2% +/- 1.5% of the radioactivity taken up was eliminated into the bile within 80 minutes. Bile flow was reduced to 0.20 +/- 0.07 microL/min, compared with 1.18 +/- 0.18 microL/g/min in untreated livers. Biliary excretion of infused 3H-LTE4 was also reduced in endotoxin-pretreated livers (31.5% +/- 6.1% compared with 61.4% +/- 3.3% without endotoxin pretreatment), whereas uptake was not significantly different. The effect of cellular hydration state on leukotriene processing was also investigated. Anisoosmotic cell volume changes did not influence uptake and biliary excretion of 3H-LTC4 and its metabolism in control livers. In endotoxin-pretreated livers, however, cell swelling induced by hypotonic perfusion media (225 mOsm/L) or by 3 mmol/L glutamine increased biliary elimination of the radioactivity taken up by 68% and 54%, respectively. Bile flow was also stimulated (0.31 +/- 0.09 microL/g/min and 0.46 +/- 0.01 microL/g/min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
STAM, Signal Transducing Adaptor Molecule, Is Associated with Janus Kinases and Involved in Signaling for Cell Growth and c-myc Induction
Authors: Toshikazu Takeshita, Tomikazu Arita, Masaya Higuchi, Hironobu Asao, Kazuhiro Endo, Hiroshi Kuroda, Nobuyuki Tanaka, Kazuko Murata, Naoto Ishii, Kazuo Sugamura
Journal: Immunity (1997)
Immunolocalization of fibroblast growth factor-1 (FGF-1), its receptor (FGFR-1), and fibroblast-specific protein-1 (FSP-1) in inflammatory renal disease
Authors: Michele Rossini, Boonyarit Cheunsuchon, Ellen Donnert, Li-Jun Ma, James W. Thomas, Eric G. Neilson, Agnes B. Fogo
Journal: Kidney International (2005)
Drugging MYCN through an Allosteric Transition in Aurora Kinase A
Authors: William Clay Gustafson, Justin Gabriel Meyerowitz, Erin A. Nekritz, Justin Chen, Cyril Benes, Elise Charron, Erin F. Simonds, Robert Seeger, Katherine K. Matthay, Nicholas T. Hertz, Martin Eilers, Kevan M. Shokat, William A. Weiss
Journal: Cancer Cell (2014)
Is Remote Disease Associated With Candida Infection a Tomato?
Authors: William J. Turner
Journal: JAMA (1985)

<h3>To the Editor.—</h3> The correspondence between Crook,<sup>1</sup>Edwards<sup>2</sup>and Coleman<sup>3</sup>recalled to me an almost forgotten history. The idea that intestinal putrefaction is a source of human ills can be traced to the ancients; I note only the connotations of "choleric" temperament and of "black bile." In the French court the clyster was in great demand. Purging was long a treatment for whatever came along, and laxatives are still found in nearly every household in the Western world. In the early years of this century, Abderhalden devised tests designed to identify and to measure degrees of autointoxication. In the second decade Cotton was famous for removing intestines of patients with "dementia praecox." Between 1930 and 1960 a large number of studies, especially by Baruk<sup>4</sup>and his school, purported to relate psychoses to neurotoxins produced by more or less specific strains of<i>Escherichia coli</i>. An annotated bibliography is
Relapsing Invasive Group B Streptococcal Infection in Adults
Authors: Lee H. Harrison
Journal: Annals of Internal Medicine (1995)

Objective: To study recurrent group B streptococcal infection in adults. Design: Patients with more than one reported group B streptococcal infection were identified through active surveillance for this infection. Sterile-site group B streptococcal isolates were evaluated for serotype and molecular subtyping using restriction endonuclease analysis of chromosomal DNA (REAC). Setting: All acute-care hospitals in Maryland. Patients: Nonpregnant residents of Maryland 18 years of age or older. Results: 22 adults had at least two group B streptococcal episodes that were separated by 2 to 95 weeks (mean, 24 weeks). Of 395 patients with invasive group B streptococcal infection who survived the first episode and were followed for at least 1 year, 17 (4.3% [95% CI, 2.6% to 6.9%]) had more than one episode. Several patients were found to have endocarditis or osteomyelitis during the second episode. Group B streptococcal isolates from both episodes were obtained from 18 of 22 patients. Of the 18 isolate pairs, 13 (72% [CI, 46% to 90%]) had identical REAC patterns; the probability that at least 13 matches would be found by chance alone was less than 0.00001. Among patients with recurrent infection caused by the same strain, the interval between episodes was shorter (mean, 14 weeks) than that among patients with recurrent infection caused by another strain (mean, 43 weeks; P = 0.05). Conclusions: Recurrent group B streptococcal infection is common among adults and in most cases appears to be caused by relapse. The optimal management of adults with a first episode of group B streptococcal infection needs to be further defined to minimize the likelihood of recurrent disease.
Abstract S5-07: SWOG S0500 – A randomized phase III trial to test the strategy of changing therapy versus maintaining therapy for metastatic breast cancer patients who have elevated circulating tumor cell (CTC) levels at first follow-up assessment
Authors: JB Smerage, WE Barlow, DF Hayes, EP Winer, B Leyland-Jones, G Srkalovic, S Tejwani, AF Schott, MA O'Rourke, DL Lew, JR Gralow, RB Livingston, GN Hortobagyi
Journal: Cancer Research (2013)

Abstract Introduction: CTC are detectable in approximately 75% of patients with metastatic breast cancer (MBC), and are elevated (≥5CTC/7.5 ml whole blood (WB)) in about half. Elevated CTC at baseline are associated with a worse prognosis, and a decline in CTC levels suggests response to therapy. We initiated a prospective randomized clinical trial (SWOG S0500) to test whether a change in chemotherapy after failure to clear CTC after one cycle of first line chemotherapy would improve outcomes of patients starting first line cytotoxic chemotherapy for MBC. Methods: Patients initiating first-line chemotherapy for MBC were enrolled. All patients had measurable or evaluable disease that included bone metastases. Patients with elevated CTC at baseline and who continued to have elevated CTC after 21 days of therapy were randomly assigned to either continue initial therapy until progression or to change to a second line chemotherapy (physician choice) immediately at cycle 2. Patients with elevated CTC at baseline, which were not elevated at the 21-day follow-up were maintained on their initial therapy. Patients without elevated CTC at baseline were followed in an observation arm. The primary endpoint was overall survival, and progression-free survival was a secondary endpoint. It was expected that approximately 500-650 patients would have to be screened to enroll 120 patients in the randomized trial. Power was 81% with 2-sided α = 0.05 to detect a 70% increase in median overall survival for patients randomized to change therapy. Three interim analyses were planned during the course of the trial. Results: From 10/1/2006 until 3/15/2012, 624 patients were registered of whom 612 were eligible. A baseline CTC was obtained in 593 (97%) eligible patients of whom 317 (53%) had elevated CTC at baseline. Thirty-one patients (10%) with elevated baseline CTC did not complete the follow-up CTC due to death, progression, withdrawal, or assay failure. Of the 286 remaining patients, 123 patients (43%) continued to have elevated CTCs after the first cycle of chemotherapy and were randomly assigned to either maintain original chemotherapy (n = 64) or switched to new chemotherapy (n = 59). Final outcome results will be analyzed in October 2013 and will be reported if released by the SWOG Data Safety Monitoring Board. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S5-07.
Gene Sampling Can Bias Multi-Gene Phylogenetic Inferences: The Relationship between Red Algae and Green Plants as a Case Study
Authors: Y. Inagaki, Y. Nakajima, M. Sato, M. Sakaguchi, T. Hashimoto
Journal: Molecular Biology and Evolution (2009)

The monophyly of Plantae including glaucophytes, red algae, and green plants (green algae plus land plants) has been recovered in recent phylogenetic analyses of large multi-gene data sets (e.g., those including >30,000 amino acid [aa] positions). On the other hand, Plantae monophyly has not been stably reconstructed in inferences from multi-gene data sets with fewer than 10,000 aa positions. An analysis of 5,216 aa positions in Nozaki et al. (Nozaki H, Iseki M, Hasegawa M, Misawa K, Nakada T, Sasaki N, Watanabe M. 2007. Phylogeny of primary photosynthetic eukaryotes as deduced from slowly evolving nuclear genes. Mol Biol Evol. 24:1592-1595.) strongly rejected the monophyly of Plantae, whereas Hackett et al. (Hackett JD, Yoon HS, Li S, Reyes-Prieto A, Rummele SE, Bhattacharya D. 2007. Phylogenomic analysis supports the monophyly of cryptophytes and haptophytes and the association of rhizaria with chromalveolates. Mol Biol Evol. 24:1702-1713.) robustly recovered the Plantae clade in an analysis of 6,735 aa positions. We suspected that the significant incongruity observed between the two studies was attributable to a bias generally overlooked in multi-gene phylogenetic estimation, rather than data size, taxon sampling, or methods for tree reconstruction. Although glaucophytes were excluded from our analyses due to a shortage of sequence data, we found that the recovery of a sister-group relationship between red algae and green plants primarily depends on gene sampling in phylogenetic inferences from <10,000 aa positions. Phylogenetic analyses of data sets with fewer than 10,000 aa positions, which can be prepared without large-scale sequencing (e.g., expressed sequence tag analyses), are practical in challenging various unresolved issues in eukaryotic evolution. However, our results indicate that severe biases can arise from gene sampling in multi-gene inferences from <10,000 aa positions. We also address the validity of fast-evolving gene exclusion in multi-gene phylogenetic analyses, in light of this gene sampling bias.
Reduced Time Points to Calculate the Composite Index
Authors: Ralph A. DeFronzo, Masafumi Matsuda
Journal: Diabetes Care (2010)

Since the original publication of the composite (Matsuda) index for the measurement of insulin sensitivity from plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT) (1), this index has been widely used by investigators throughout the world. According to Scopus, more than 1,000 articles have cited the original article (1) during the last 10 years, and several modifications of this index have been published (2,3). Although the basic idea is to use the plasma insulin and glucose areas under the curve (AUCs), the actual time points at which plasma insulin and glucose …
After Barney Clark: Reflections on the Utah Artificial Heart Program
Authors: Arthur L. Caplan
Journal: JAMA (1985)

This book is the outcome of a conference held in October 1983, seven months after the death of Dr Barney Clark. The conference was organized in order to provide an opportunity for Dr Clark's caregivers and a number of invited experts to reflect about some of the ethical, legal, economic, and social issues that arose as a result of the effort to permanently implant a total artificial heart into Dr Clark's chest. Since the Clark experiment, the clinical component of the artificial heart program at Utah has shifted to the Humana-Audubon Hospital in Louisville, Ky. This shift and the subsequent implantation by Dr William DeVries and his colleagues of a second device in William Schroeder, devices in two other patients (Murray Haydon and the late Jack Burcham), and implantation of a device in Sweden, have stimulated a renewed debate about the desirability and feasibility of undertaking implants of a pneumatically
The Case for Kidney Donation Before End-of-Life Care
Authors: Paul E. Morrissey
Journal: The American Journal of Bioethics (2012)

Donation after cardiac death (DCD) is associated with many problems, including ischemic injury, high rates of delayed allograft function, and frequent organ discard. Furthermore, many potential DCD donors fail to progress to asystole in a manner that would enable safe organ transplantation and no organs are recovered. DCD protocols are based upon the principle that the donor must be declared dead prior to organ recovery. A new protocol is proposed whereby after a donor family agrees to withdrawal of life-sustaining treatments, premortem nephrectomy is performed in advance of end-of-life management. Since nephrectomy should not cause the donor's death, this approach satisfies the dead donor rule. The donor family's wishes are best met by organ donation, successful outcomes for the recipients, and a dignified death for the deceased. This proposal improves the likelihood of achieving these objectives.
Subclinical malabsorption in Thailand.
Authors: F. A. Klipstein
Journal: BMJ (1968)

beyond dispute that the better a doctor's post- graduate experience the more he has to com- promise his medical standards in N.H.S. general practice.Tradition has made many general practitioners and consultants believe that these two areas of medical practice are mutually exclusive, but, as many of us who have experience of North America know, and indeed, as the report clearly showed, this is simply not so.While it may be true that the Canadian general practitioner mentioned in the report admitted many patients to hospital whom his British colleague would care for at home, the report should have underlined that he similarly cares for a number of patients whom his British counterpart would have had to " lose" to the local hospital.The number of general-practitioner beds in type I (acute) hospitals in England and Wales has remained static at about 7,000 for the past five years-about 300 hospitals offer- ing these facilities.It is lamentable and sig- nificant that not one teaching hospital is included in this list.It is depressing to see new hospitals developed and old hospitals modernized without any reference to the needs of the general practitioners in the dis- trict.It is up to the Ministry to break down the barriers, and this would represent the cheapest method of retaining young practi- tioners in this country.It only requires foresight.-Iam, etc., Bottisham,
Shedding of Low-Density Lipoprotein Receptor–related Protein-1 in Acute Respiratory Distress Syndrome
Authors: Malgorzata Wygrecka, Jochen Wilhelm, Ewa Jablonska, Dariusz Zakrzewicz, Klaus T Preissner, Werner Seeger, Andreas Guenther, Philipp Markart
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Low-density lipoprotein receptor–related protein-1 (LRP-1) mediates the endocytic clearance of various proteinases, including matrix metalloproteinases (MMPs). The ectodomain of LRP-1 can be shed from the cell surface, releasing a soluble form of this receptor (sLRP-1), which antagonizes ligand endocytosis by cellular LRP-1.To assess if increased LRP-1 shedding occurs in the lungs of patients with acute respiratory distress syndrome (ARDS) and may lead to the accumulation of MMPs and subsequent tissue injury.We determined sLRP-1 levels in bronchoalveolar lavage fluids (BALF) from 46 patients with ARDS and their correlation with MMP concentration and disease severity. In complementary in vitro studies, we investigated the mechanisms underlying the LRP-1 release from the cell surface and its impact on MMP cellular uptake.sLRP-1 levels were significantly elevated in BALF but not in plasma from patients with ARDS compared with control subjects and further increased in the later course of the disease. Baseline BALF sLRP-1 concentration was positively correlated with disease severity and significantly higher in nonsurvivors compared with survivors. The presence of ARDS BALF enhanced LRP-1 shedding from cultured lung fibroblasts but not from alveolar type II cells or macrophages. This process was blocked when ARDS BALF was supplemented with metalloproteinase inhibitor resulting in enhanced cellular uptake and degradation of MMP-2 and -9. Accordingly, sLRP-1 BALF concentration in patients with ARDS was positively correlated with MMP levels and laminin, a marker of basement membrane disruption.Increased LRP-1 shedding prevents the cellular clearance of MMPs and might thereby contribute to tissue destruction in ARDS lungs.