tbuckley/cabot-search huggingface dataset:
Abstract 96: Estrogen modulates cellular and molecular markers of hypoxic tumor microenvironment in thyroid cancer.
Authors: Shilpi Rajoria, Elyse Hanly, Andrea George, Robert Suriano, Jan Geliebter, Masoud Saman, Stimson Schantz, Raj K. Tiwari
Journal: Cancer Research (2013)

Abstract Thyroid proliferative diseases are three to four times more prevalent in women than in men. Our laboratory has systemically elucidated the role of estrogen in thyroid cancer as a promoter of increased aggressiveness, however the role of estrogen within the hypoxic environment of thyroid cancer is not known. Based on our observation that estrogen promotes neo-vascularization of thyroid tumors by modulating angiogenic factors, vascular endothelial growth factors (VEGF) and matrix metalloproteinases (MMPs), we hypothesize that tumor hypoxia synergizes with estrogen to produce an inflammatory microenvironment that helps the progression of thyroid cancer. We observed that thyroid cancer cells are responsive to hypoxic conditions and estrogen induces hypoxia inducible factor-1α (HIF-1α) nuclear translocation in these cells. Furthermore, estrogen and hypoxia modulate the HIF-1 signaling in thyroid cancer cells which is abrogated by the anti-estrogen fulvestrant and the HIF-1 inhibitor YC-1 (3-(5’-hydroxymethyl-2’-furyl)-1-benzylindazole). Conditioned medium from estrogen treated thyroid cancer cells lead to enhanced migration and tubulogenesis of human umbilical vein endothelial cells (HUVECs), due to secretion of hypoxia and estrogen responsive proteins by thyroid cancer cells leading to increased angiogenesis of endothelial cells. This phenomenon was abrogated by HIF-1 inhibitor. These results demonstrate for the first time that estrogen signaling pathways mimic the signaling pathways in the hypoxic environment in thyroid cancer cells, thus suggesting that estrogen potentially mimics oxygen deprivation at the molecular level to produce an inflammatory tumor microenvironment thus fostering the progression of thyroid cancer. We conclude that apart from the direct activity of estrogen on thyroid cancer phenotype, estrogen also modulates the tumor microenvironment specifically maintaining hypoxic conditions which may be essential for thyroid cancer progression and/or metastases. Citation Format: Shilpi Rajoria, Elyse Hanly, Andrea George, Robert Suriano, Jan Geliebter, Masoud Saman, Stimson Schantz, Raj K. Tiwari. Estrogen modulates cellular and molecular markers of hypoxic tumor microenvironment in thyroid cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 96. doi:10.1158/1538-7445.AM2013-96
Diseases of Metabolism: Detailed Methods of Diagnosis and Treatment
Authors: Will G. Ryan
Journal: JAMA (1965)

Thannhauser's Textbook of Metabolism and Metabolic Disorders. Vol II.Edited by Nepomuk Zollner. American edition translated and edited by Solomon Estren. 2nd ed. 968 pp, 288 illus. $19.75. Grune & Stratton, 381 Park Ave S, New York 16, 1964  Any attempted definition of an internist would meet with doubtful success, and the same difficulties arise in trying to define metabolism. This problem we find reflected in the considerable variation of contents which these two books exhibit. In common, the authors cover the metabolism of proteins, carbohydrates, fat (Thannhauser, Vol I), and minerals and diseases thereof, along with diseases of nucleic acid and porphyrin metabolism (Thannhauser, Vol I and II). In other areas they diverge considerably.  Dr. Duncan's book, basically similar in format to previous editions, is somewhat expanded to a total of 1,551 pages. While both carbohydrate and protein metabolism receive good discussion, the section on fat metabolism is somewhat
The genetic basis of spondyloarthritis
Authors: J. D. Reveille
Journal: Annals of the Rheumatic Diseases (2011)

Modern technological innovations have advanced our understanding of the genetic basis of spondyloarthritis. In ankylosing spondylitis (AS), where the major histocompatibility complex (MHC) accounts for nearly half of the predisposition, most comes from HLA-B27, for which 65 subtypes are now recognised, although other genes are also at work including HLA-B60 (B*40:01). Other genes have been identified, including those involved in peptide editing for loading onto class I MHC molecules (ERAP1) and cytokine genes such as interleukin 1A (IL-1A) and those involved in the Th17 network (IL-23R, an association seen primarily in Caucasians) and others. In acute anterior uveitis, these associations are also seen as well as a region on chromosome 9p and genes whose confirmation is under way. Psoriasis and psoriatic arthritis fall into this disease spectrum, with the largest region of susceptibility coming from the MHC (most likely HLA-C, ie, C*06:02 although additional influences are also being implicated), and most of the other genetic susceptibility coming from genes involved in cytokine production, specifically genes in the Th17 pathway (IL-12B, IL-23A and IL-23R, the latter, like in AS, not seen in Asians), genes in the nuclear factor κB pathway (TNFAIP3 and TNIP1) and genes in the Th2 pathway (IL-4 and IL-13). Given that more than half of patients with AS have evidence on colonoscopy of at least occult inflammatory bowel disease (IBD), it is not surprising that shared genetic influences are operative. In IBD, genes important in the innate immune response (NOD2), autophagy (ATG6L1) and regulation of the IL-23 pathway (IL-23R) play a role in disease susceptibility.
Direct to consumer advertising of prescription drugs
Authors: B. Mintzes
Journal: BMJ (2008)

Even attenuated forms such as cross border advertising can lead to unnecessary harm

Are there public health consequences when regulators turn a blind eye to cross border advertising that contravenes national laws? Although Canada prohibits direct to consumer advertising of prescription drugs, no steps are taken to prevent US advertising from reaching the Canadian public. The linked study by Law and colleagues (doi: 10.1136/bmj.a1055), provides compelling evidence that this does have consequences for public health and of the need for better regulatory oversight.1

Direct to consumer advertising from the United States reaches Canadians via cable television and US magazines sold in Canada. Law and colleagues found that cross border advertising increased prescribing of a minimally effective drug with a poor safety profile,2 which subsequently led to its withdrawal.3

French speaking Canadians, who mainly live in Quebec, watch less US television than their English speaking compatriots and are less exposed to US direct to consumer advertising. Law and colleagues used this difference to examine the effects of US advertising campaigns on prescribing rates. Three drugs met the inclusion criteria of the study on the basis of timing of approval and advertising—tegaserod, etanercept, and mometasone. A clear effect was …
THE RELATION OF EAR CONDITIONS TO BATHING
Authors: W. I. Daggett, R. Cove-Smith
Journal: BMJ (1929)

I[DICAL JKOt 3. Irradiatioil of rabbits with an identical technique, aftei inlfection with virulenit staphylococcus, gives no pro- tectioni. 4. Experimenlts indicate that the results are not due to the productionof vitamins (A or D).
Oral Anti-CD3 Antibody Treatment Induces Regulatory T Cells and Inhibits the Development of Atherosclerosis in Mice
Authors: Naoto Sasaki, Tomoya Yamashita, Masafumi Takeda, Masakazu Shinohara, Kenji Nakajima, Hideto Tawa, Takashi Usui, Ken-ichi Hirata
Journal: Circulation (2009)

Accumulating evidence suggests that several subsets of regulatory T cells that actively mediate immunologic tolerance play crucial roles in atherogenesis. Recently, orally administered anti-CD3 monoclonal antibody has been shown as an inducer of novel regulatory T cells expressing latency-associated peptide (LAP) on their surface, which potently prevents systemic autoimmunity. In the present study, we hypothesized that oral anti-CD3 antibody treatment may inhibit atherosclerosis in mice.Six-week-old apolipoprotein E-deficient mice on a standard diet were orally given anti-CD3 antibody or control immunoglobulin G on 5 consecutive days, and atherosclerosis was assessed at age 16 weeks. Oral administration of anti-CD3 antibody significantly reduced atherosclerotic lesion formation and accumulations of macrophages and CD4(+) T cells in the plaques compared with controls. We observed a significant increase in LAP(+) cells and CD25(+)Foxp3(+) cells in the CD4(+) T-cell population in anti-CD3-treated mice, in association with increased production of the antiinflammatory cytokine transforming growth factor-beta and suppressed T-helper type 1 and type 2 immune responses. Neutralization of transforming growth factor-beta in vivo abrogated the preventive effect of oral anti-CD3 antibody.Our findings indicate the atheroprotective role of oral anti-CD3 antibody treatment in mice via induction of a regulatory T-cell response. These findings suggest that oral immune modulation may represent an attractive therapeutic approach to atherosclerosis.
STUDIES ON A BACTERICIDAL AGENT EXTRACTED FROM A SOIL BACILLUS
Authors: René J. Dubos, Carlo Cattaneo
Journal: The Journal of Experimental Medicine (1939)

A cell-free extract of cultures of an unidentified soil bacillus, which exerts a bactericidal effect on Gram-positive microorganisms, has been described in previous reports; the first active preparations which were obtained were found to contain a protein precipitable at pH 4.5. It is shown in the present report that the bactericidal agent can be obtained in an active form free of protein. The new purified preparations retain all the activity of the original material, both in vitro and in vivo.
Iron deficiency: A concise review
Authors: Jay Umbreit
Journal: American Journal of Hematology (2005)

Iron deficiency is a major worldwide health problem. There is recent evidence that the anemia is only the last manifestation of the syndrome and that symptoms occur before the anemia is manifest. Advances in outlining the physiology of iron deficiency have been made, gaps remain in the current understanding. While oral iron supplement remains the mainstay, some indications for the intravenous administration have developed. This review will highlight the epidemiology, physiology, clinical presentation, and treatment options. Am. J. Hematol. 78:225–231, 2005. © 2005 Wiley-Liss, Inc.
Is human giardiasis caused by two different Giardia species?
Authors: Jon Jerlström-Hultqvist, Johan Ankarklev, Staffan G. Svärd
Journal: Gut Microbes (2010)

We have recently sequenced the genome of the human Giardia intestinalis assemblage B isolate GS.1 Comparisons to the earlier sequenced genome of the human assemblage A isolate WB showed that the average amino acid identity in 4300 orthologous proteins was only 78%. Here we discuss these results in the light of new genome sequencing data from the hoofed-animal assemblage E (isolate P15, isolated from a pig) and further characterization of assemblage A and B isolates from humans. There is a highly conserved set of core genes (4557 genes, 91% of genome) common to all isolates. The largest genomic differences are found in variable, Giardia-specific gene families and a large number of chromosomal rearrangements were detected, even between different chromosomes. Surprisingly, the assemblage E and A isolates are more similar at the amino-acid level than the two human isolates are to each other. This strengthens our earlier data suggesting that humans are infected by two different species of Giardia.
COX 2 inhibitors can affect the stomach lining
Authors: D. Josefson
Journal: BMJ (1999)

A new class of analgesics designed to be less ulcerogenic than traditional non-steroidal anti-inflammatory drugs may not protect the gastric lining after all, according to a University of California study (Nature Medicine 1999;5:1415-23, 1348-9).

Their ulcerogenic effect may stem from their antiangiogenic properties, and as such they may be useful anticancer drugs.

The analgesics, agents known as selective cyclo-oxygenase-2 (COX 2) inhibitors, were specifically designed to be less harmful to the gastric mucosal …
ENDEMIC CRETINISM: POSSIBLE ROLE FOR THYROID AUTOIMMUNITY
Authors: StevenC. Boyages, GlenF. Maberly, Jin Chen, Jean-Pierre Halpern, CreswellJ. Eastman, Wang Zhen-Hua, ReindertD. Van Der Gaag, HemmoA. Drexhage
Journal: The Lancet (1989)
An evaluation of elongation factor 1 alpha as a phylogenetic marker for eukaryotes
Authors: A. J. Roger, O. Sandblom, W. F. Doolittle, H. Philippe
Journal: Molecular Biology and Evolution (1999)

Elongation factor 1 alpha (EF-1 alpha) is a highly conserved ubiquitous protein involved in translation that has been suggested to have desirable properties for phylogenetic inference. To examine the utility of EF-1 alpha as a phylogenetic marker for eukaryotes, we studied three properties of EF-1 alpha trees: congruency with other phyogenetic markers, the impact of species sampling, and the degree of substitutional saturation occurring between taxa. Our analyses indicate that the EF-1 alpha tree is congruent with some other molecular phylogenies in identifying both the deepest branches and some recent relationships in the eukaryotic line of descent. However, the topology of the intermediate portion of the EF-1 alpha tree, occupied by most of the protist lineages, differs for different phylogenetic methods, and bootstrap values for branches are low. Most problematic in this region is the failure of all phylogenetic methods to resolve the monophyly of two higher-order protistan taxa, the Ciliophora and the Alveolata. JACKMONO analyses indicated that the impact of species sampling on bootstrap support for most internal nodes of the eukaryotic EF-1 alpha tree is extreme. Furthermore, a comparison of observed versus inferred numbers of substitutions indicates that multiple overlapping substitutions have occurred, especially on the branch separating the Eukaryota from the Archaebacteria, suggesting that the rooting of the eukaryotic tree on the diplomonad lineage should be treated with caution. Overall, these results suggest that the phylogenies obtained from EF-1 alpha are congruent with other molecular phylogenies in recovering the monophyly of groups such as the Metazoa, Fungi, Magnoliophyta, and Euglenozoa. However, the interrelationships between these and other protist lineages are not well resolved. This lack of resolution may result from the combined effects of poor taxonomic sampling, relatively few informative positions, large numbers of overlapping substitutions that obscure phylogenetic signal, and lineage-specific rate increases in the EF-1 alpha data set. It is also consistent with the nearly simultaneous diversification of major eukaryotic lineages implied by the "big-bang" hypothesis of eukaryote evolution.
Combined Tetanus, Diphtheria, and 5-Component Pertussis Vaccine for Use in Adolescents and Adults
Authors: Michael E. Pichichero
Journal: JAMA (2005)

Increasing reports of pertussis among US adolescents, adults, and their infant contacts have stimulated vaccine development for older age groups.To assess the immunogenicity and reactogenicity of a tetanus-diphtheria 5-component (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3) acellular pertussis vaccine (Tdap) in adolescents and adults.A prospective, randomized, modified double-blind, comparative trial was conducted in healthy adolescents and adults aged 11 through 64 years from August 2001 to August 2002 at 39 US clinical centers.A single 0.5-mL intramuscular dose of either Tdap or tetanus-diphtheria vaccine (Td).Antibody titers to diphtheria and tetanus toxoids for Tdap and Td were measured in sera collected from subsets of adolescents and adults, before and 28 days after vaccination. For pertussis antigens, titers in sera from Tdap vaccinees were assessed vs those from infants who received analogous pediatric diphtheria-tetanus-acellular pertussis vaccine (DTaP) in a previous efficacy trial. Safety was assessed via solicited local and systemic reactions for 14 days and adverse events for 6 months following vaccination.A total of 4480 participants were enrolled. For both Tdap and Td, more than 94% and nearly 100% of vaccinees had protective antibody concentrations of at least 0.1 IU/mL for diphtheria and tetanus, respectively. Geometric mean antibody titers to pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3 exceeded (by 2.1 to 5.4 times) levels in infants following immunization at 2, 4, and 6 months with DTaP. The incidence of solicited local and systemic reactions and adverse events was generally similar between the Tdap and Td groups.This Tdap vaccine elicited robust immune responses in adolescents and adults to pertussis, tetanus, and diphtheria antigens, while exhibiting an overall safety profile similar to that of a licensed Td vaccine. These data support the potential routine use of this Tdap vaccine in adolescents and adults.
Abstract 4622: PAM4-antigen levels in the serum of patients with pancreatic carcinoma: Early detection of disease and correlation with responses to radioimmunotherapy
Authors: David V. Gold, Guy Newsome, David E. Modrak, Heather Horne, William A. Wegener, David M. Goldenberg
Journal: Cancer Research (2010)

Abstract Background: A serum-based enzyme immunoassay (EIA) employing MAb-PAM4 demonstrates high specificity and sensitivity for detection of advanced pancreatic carcinoma (PC). We are currently exploring use of the immunoassay as a means to detect early-stage PC, as well as detection of nascent disease progression or relapse during routine post-treatment follow-up. We now also report initial results that provide correlation of serum PAM4-antigen levels with responses to radiolabeled PAM4 therapy. Methods: The PAM4-based EIA was employed for detection and quantitation of antigen in the serum of pancreatic carcinoma patients with known stage of disease (N=68). An additional 11 patients with stage-4 disease who participated in an ongoing phase-1b clinical trial to evaluate the combination of 90Y-hPAM4 IgG, (clivatuzumab tetrexate) radioimmunotherapy with low-dose, radiosensitizing, gemcitabine (Gem) were also examined. Serum specimens from this latter group were collected at baseline prior to treatment, at the end of the 4-week treatment cycle, and again at 4 weeks post-treatment (week 8 from baseline), when a CT scan was performed to determine tumor response. Results: Overall, the sensitivity of the immunoassay for detection of PC was 81%, with a 5% false-positive rate for the healthy volunteers (N=19). When examined by stage of disease, sensitivity rates were 91%, 86% and 62% for stages 3/4 advanced disease, stage-2, and stage-1 PC, respectively. For those patients who had treatment with 90Y-hPAM4 + Gem, a decrease in antigen levels greater than 40%, observed at the end of the treatment cycle (4 weeks), with sustained decline in the antigen levels at the 8-week post-treatment evaluation, provided presumptive evidence of tumor response, either stable disease (SD, N=2) or partial response (PR, N=5) by CT RECIST criteria. None of the patients with progressive disease (N=4) had a sustainable decrease in serum levels of PAM4-antigen, whereas all of the responders did. The median decrease in serum PAM4-mucin levels at the 8-week follow-up evaluation timepoint was 54% (range: 47% - 98% decrease), with a median tumor response (only SD and PR responders) being a decrease in tumor size of 37% (range: 46% decrease to 4% increase), from a baseline median primary tumor size of 10.0 cm (range 2.6 - 12.1 cm). Conclusions: These results suggest that the PAM4-based immunoassay should be further evaluated for use in the detection of early pancreatic carcinoma, as well as to evaluate tumor response to therapy. (Supported in part by grant CA096924 from the NIH.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4622.
Minilaparoscopy in the Diagnosis of Cirrhosis: Superiority in Patients with Child-Pugh A and Macronodular Disease
Authors: I. Helmreich-Becker, P. Schirmacher, U. Denzer, A. Hensel, K. H. Meyer zum Büschenfelde, A. W. Lohse
Journal: Endoscopy (2003)

Background and Study Aims: The diagnosis of cirrhosis has prognostic and therapeutic implications, but early forms are difficult to diagnose. Laparoscopy with histology has been reported to be superior to histology alone, but is often considered to be too invasive. This study aimed to assess whether minilaparoscopy offers similarly high sensitivity coupled with only minor invasiveness. Patients and Methods: Minilaparoscopy with biopsy was performed in 226 consecutive patients with chronic liver disease. Cirrhosis was diagnosed macroscopically primarily on the basis of nodularity in a nontumorous liver. A histological diagnosis using the modified Knodell score was made without knowledge of the macroscopic assessment. Results: Biopsies from 22 patients were inadequate for histological assessment, and 16 of these were considered to be cirrhotic from macroscopic observation. Out of 204 liver biopsies, 94 (46 %) were macroscopically identified as cirrhotic; 68/204 (33 %) showed stage 5 or 6 fibrosis (incomplete or complete cirrhosis). Histological understaging occurred mainly in patients who were otherwise diagnosed as having early Child-Pugh A cirrhosis, macroscopically incomplete cirrhosis and macronodular cirrhosis; 4/204 (2 %) of patients with cirrhosis histologically were understaged macroscopically. Conclusions: Macroscopic evaluation during minilaparoscopy increases the sensitivity of detection of liver cirrhosis, compared with biopsy alone, by more than 30 %. Because of its minimal invasiveness, minilaparoscopy combined with biopsy is recommended as a superior method for the staging of chronic liver disease.
Is There a Role for the Endoscopic Treatment of Pain from Chronic Pancreatitis?
Authors: Grace H. Elta
Journal: New England Journal of Medicine (2007)

The treatment of the pain of chronic pancreatitis continues to be problematic. Although severe calcific pancreatitis can be asymptomatic, it can cause disabling pain daily. Medical management with abstinence from alcohol, a low-fat diet, supplementary pancreatic enzymes, and nonnarcotic analgesic agents is the first step in therapy but is often ineffective. Pain management with the long-term use of narcotics is common but is often unsatisfactory because of tolerance to the medication, loss of efficacy, and complications of drug dependency. Injections of octreotide are used for pain control, but efficacy studies have been contradictory. Notably, the placebo response rate in patients . . .