tbuckley/cabot-search huggingface dataset:
THE USE OF BISMUTH COMPOUNDS IN SYPHILOTHERAPY
Authors: EDMUND N. WALSH
Journal: JAMA (1941)

In the past twelve years the treatment of all types of syphilis at the University of Chicago Clinics has been planned with the use of much more bismuth than has usually been considered as standard or optimum treatment. In this report we wish to evaluate the results of such treatment of early syphilis, asymptomatic neurosyphilis and tabes dorsalis over a ten year period and compare these results, as far as possible, with corresponding data from the Cooperative Clinical Group studies.  PRESENT DAY STATUS OF BISMUTH IN SYPHILOTHERAPY  Since Sazerac and Levaditi 1 in 1921 first popularized bismuth as an antisyphilitic drug, it has gone through much the same cycle as was previously traversed by the roentgen ray and arsphenamine and as we have recently seen carried out with sulfanilamide. There was first a period of overoptimism, especially on the part of some members of the French school who hailed bismuth
A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis
Authors: Giovanni Palladini, Ute Hegenbart, Paolo Milani, Christoph Kimmich, Andrea Foli, Anthony D. Ho, Marta Vidus Rosin, Riccardo Albertini, Remigio Moratti, Giampaolo Merlini, Stefan Schönland
Journal: Blood (2014)
Research Ethics Boards: The Protection of Human Subjects
Authors: Valia S Lestou, Nancy Ondrusek, Morris A Blajchman
Journal: PLoS Medicine (2006)

Joal HillI read with interest the debate about for-profi t versus non-profi t institutional review boards (IRBs) [1], but was disappointed that no one addressed the ability (or inability) of for-profi t IRBs to review studies with the local context of research subjects in mind and then monitor what actually occurs during the consent process throughout the research trial.To my mind the "bigness" of for-profi t IRBs may be more of an impediment in protecting research subjects than their inherent confl ict of interest.Our IRB has reviewed consent forms approved by central/for-profi t IRBs that contained obvious errors such as schemas that did not match protocol narrative and use of eight point font in a study of geriatric subjects.Even when the initial review is outstanding, it seems a practical impossibility for a single IRB to provide meaningful monitoring of the actual consent process and implementation of the protocol at sites throughout the country.The greater "effi ciency" of for-profi t IRBs is only a meaningful benefi t if increased speed can be shown not to occur at the expense of careful review of consent forms, real understanding of the local research context, and a commitment to audit the informed consent process throughout the study for the protection of research subjects, including ongoing education and advice for researchers and their teams.This is not to say that all local IRBs perform this function as they should, but it does seem almost impossible for one IRB to perform local review and oversight for research sites around the nation in a way that really makes a difference for the men, women, and children who give of their time and their bodies so that society can benefi t.
Endotracheal Metastasis From Squamous Cell Cancer of the Head and Neck
Authors: Ba D. Nguyen, Panol C. Ram, Michael C. Roarke
Journal: Clinical Nuclear Medicine (2008)

Lung cancer is the main malignancy with frequent endotracheal and endobronchial dissemination. Extrapulmonary sources of airway metastasis are less common, predominantly seen with breast, colorectal, and renal neoplasms. Head and neck cancer represents only a small fraction of tumors with tracheal luminal metastasis. We present 2 such rare cases with F-18 FDG PET/CT imaging. These 2 companion cases show in one instance an obvious hypermetabolic endotracheal lesion and in the other one a discrete airway metastasis overlooked by chest CT and diagnosed by PET with coregistered CT.
Abstract B22: Re-expression of miR-200 by natural agents regulates the expression of PTEN and MT1-MMP in pancreatic cancer
Authors: Shadan Ali, Omar Soubani, Azfur Ali, Farah Logna, Philip Philip, Fazlul Sarkar
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Membrane type-1 matrix metalloproteinase (MT1-MMP) is often activated and expressed in tumor cells with significant invasive properties, and is associated with poor prognosis of patients. This could partly be due to deregulated expression of microRNAs (miRNAs) which regulates the expression of MT1-MMP and PTEN (Phosphatase and tensin homolog) contributing to tumor invasion and metastasis. Experimental Procedure: We initially compared the expression profile of miR-200 family, PTEN and MT1-MMP expression in six pancreatic cancer (PC) cell lines by qRT-PCR and western blot analysis. Based on our initial findings, we chose BxPC-3, MIAPaCa-2, and MIAPaCa-2-GR cells for further mechanistic studies. We assessed the effect of two separate novel agents CDF, (a synthetic analogue of curcumin) and BR-DIM (a natural agent) on PC cells. Results: We found loss of expression of miR-200a, b, and c in chemo-resistant PC cell lines, which was correlated with loss of PTEN and over-expression of MT1-MMP. The expression of miR-200 family and PTEN was significantly re-expressed whereas the expression of MT1-MMP was down-regulated by CDF and BR-DIM treatment. Forced over-expression or silencing of miR-200c, followed by either CDF or BR-DIM treatment of MIAPaCa-2 cells altered the morphology of cells, wound-healing capacity, colony formation, and the expression of MT1-MMP and PTEN. Conclusion: These results provide strong experimental evidence showing that the loss of miR-200 family and PTEN expression, and increased level of MT1-MMP leads to aggressive behavior of PC cells, which could be attenuated through re-expression of miR-200c by CDF and/or BR-DIM treatment, suggesting that these agents could be useful for treatment.
cimp1, A Novel Astacin Family Metalloproteinase Gene from East African Cichlids, Is Differentially Expressed Between Species During Growth
Authors: T. Kijimoto
Journal: Molecular Biology and Evolution (2005)

Lake Victoria cichlid fishes are excellent examples of explosive adaptive radiation. Although Lake Victoria cichlids are believed to have arisen during a short period (∼14,000 years), they have various species-specific phenotypes. One important phenotype that distinguishes each species is the shape of the jaw, which has diverged to adapt to the wide variety of trophic habitats present in the lake. Here we demonstrate a new approach to investigate the diversification of cichlid jaw morphology at the genetic level by examining differentially expressed genes. We used a DNA chip to compare gene expression levels between closely related cichlid fishes. This analysis indicated that the expression of some genes differed in the larvae of two cichlid species. One such clone encodes a new astacin family metalloproteinase. The expression level of the isolated gene, named cimp1, was analyzed in more detail by real-time quantitative reverse transcription-polymerase chain reaction. A significant difference in cimp1 expression was observed between two Haplochromis cichlid species during development. Using in situ hybridization, we found that this gene is expressed only in head and gill epithelia. Biochemical analysis showed that cichlid metalloproteinase 1 (CiMP1) has proteolytic activity, a common attribute of all astacin family proteins. Because some astacin family proteins contribute to morphogenesis in animals, CiMP1 is expected to participate in species-specific head morphogenesis in cichlids. This is the first study to demonstrate that differentially expressed genes among cichlids can be identified using a DNA chip.
The Role of Proteinase-activated Receptor-2 in Idiopathic Pulmonary Fibrosis: Is There Really Novel Therapeutic Potential Here?
Authors: Malgorzata Wygrecka, Grazyna Kwapiszewska, Ewa Jablonska, Susanne von Gerlach, Ingrid Henneke, Dariusz Zakrzewicz, Andreas Guenther, Klaus T. Preissner, Philipp Markart
Journal: American Journal of Respiratory and Critical Care Medicine (2012)
The Anemia of Primary Autonomic Failure and its Reversal with Recombinant Erythropoietin
Authors: Italo Biaggioni
Journal: Annals of Internal Medicine (1994)

Objective: To determine if chronic sympathetic deprivation is associated with anemia and a low erythropoietin response. Design: Survey of the prevalence and characteristics of anemia in patients with severe primary autonomic failure. Setting: A referral service for autonomic failure in a tertiary teaching hospital. Patients: 84 patients with primary autonomic failure who had symptomatic orthostatic hypotension. Intervention: Open-label trial with human recombinant erythropoietin. Results: Anemia was present in 32 of 84 patients (38%; 95% CI, 27% to 50%). Plasma norepinephrine levels, measured in patients standing upright, were lower in the patient group with lower hemoglobin levels. Mean values in 22 patients with a hemoglobin level of less than 120 g/L were as follows: hemoglobin, 108 g/L (range, 87 to 118 g/L); hematocrit, 0.33; corrected reticulocyte counts, 0.008; mean corpuscular volume, 89 fL (89 microns3); serum iron, 16.5 µmol/L (92 µg/dL); total iron binding capacity, 43.3 µmol/L (242 µg/dL); ferritin, 184 µg/L; serum vitamin B12, 410 pmol/L (556 pg/mL); and serum folate, 22.7 nmol/L (10 ng/mL). No relation was found between serum erythropoietin and blood hemoglobin levels. In seven of nine patients with autonomic failure who had hemoglobin levels less than 120 g/L, serum erythropoietin levels decreased below the 95% confidence interval corresponding to patients with iron deficiency anemia. Therapy with recombinant erythropoietin improved mean hemoglobin levels (from 108 to 133 g/L) in all patients treated (n = 5) at relatively low doses (25 to 50 units/kg body weight, subcutaneously, three times a week). Conclusions: Our data support the hypothesis that the sympathetic nervous system stimulates erythropoiesis in humans because anemia is a frequent occurrence in patients with severe autonomic failure and is associated with a blunted erythropoietin response.
"POSSIBILITY OF RECOVERY FROM DIABETES UNDER INSULIN"
Authors: Joseph C. Ohlmacher
Journal: JAMA (1925)

<h3>To the Editor:</h3> —InThe Journal, April 18, there is editorial reference to an anatomic study of the pancreas, made by Boyd and Robinson, in a diabetic boy, who died from an accident. Under an insulin regimen his carbohydrate tolerance had increased "threefold," with corresponding improvement in his general physical condition. Changes were seen that were interpreted as evidence of regeneration of the cells of the islets. It is presumed, therefore, that the insulin treatment, by relieving the strain placed on the already functionally deficient islet system, allowed the new islets to develop and assume their normal functional capacity. I am convinced that this should be interpreted as anatomic evidence of progress toward recovery. Early favorable cases will recover under insulin, and increased carbohydrate tolerance should be interpreted on an anatomic basis. In 1904 (<i>Am. J. M. Sc</i>.<b>3</b>:287-307 [Aug.] 1904) I attempted to show that the islands of
Isolation and Characterization of an Abnormal Human Intrinsic Factor
Authors: Max Katz, Carol S. Mehlman, Robert H. Allen
Journal: Journal of Clinical Investigation (1974)

A patient has been described previously who presented at age 13 with vitamin B12 (B12) deficiency secondary to a functionally abnormal intrinsic factor (IF). IF has now been isolated from the gastric juice of the patient, his sister, and both parents, who are first cousins, by using affinity chromatography on B12-Sepharose. Patient IF appeared normal in terms of (a) B12 binding, (b) mol wt, (c) total amino acid and carbohydrate composition, and (d) immunodiffusion with rabbit anti-patient and anti-normal IF sera. After adsorption with normal IF, however, anti-patient IF serum precipitated the various IFs as follows: patient IF (> 95%); mother, father, and sister IF (50%); and normal IF (< 10%). Additional adsorption with mother, father, or sister IF completely inhibited the precipitation of patient IF. The association constant determined for patient IF-B12 and human ileal mucosal homogenates (0.1 × 109 M-1) was 60-fold lower than that determined with normal IF-B12 (6.0 × 109 M-1). Intermediate amounts of ileal IF-B12 binding were observed with mother, father, and sister IF-B12. These in vitro studies were supported by multiple Schilling tests, performed with a totally gastrectomized volunteer, that gave the following mean urinary excretions of [57Co]B12: free B12 (0.5%); + patient gastric juice (2.6%); + mother or father gastric juice (17%); and + normal gastric juice (26%). These studies demonstrate that the patient is homozygous and that the mother, father, and sister are heterozygous for a structurally abnormal IF that has a markedly decreased, but not absent, affinity for ileal IF-B12 receptors. These studies also indicate that the B12 and ileal binding sites are located on different portions of the IF molecule.
Tumors of the Hand
Authors: W Bruce Conolly, Jan van Loon
Journal: Journal of the Royal Society of Medicine (2004)

Because the hand, like the face, is the first encounter of a patient by any clinician, a basic knowledge of hand tumours is relevant to all clinical practice. Tumours can arise from any of the six main tissues of the hand. Most tumours of the hand are not true neoplasms but the result of classic disease states—trauma, infection, inflammatory disease, metabolic disorder, degenerative disorder, congenital anomaly. The clinician then needs to know which tumours should be investigated and referred on to a specialist. Egloff's book, published in association with the Federation of Societies for Surgery of the Hand, provides a near-comprehensive review. Tumours of the hand and upper extremity were the subject of an issue of Hand Clinics this year (2004; 20: No. 2) but no book has been devoted solely to the subject since the 1988 Tumours of the Hand by Glicenstein, Ohana and Leclercq (Springer Verlag).

Two omissions are noteworthy. First, 90% of hand tumours are ganglia, and Egloff and his team decided to exclude these because they are not true tumours and their treatment is to be found in all textbooks. In our opinion, ganglia deserved a place because they come into the different diagnosis of tumours; a ganglion can be hard to distinguish from a giant cell tumour of tendon sheath, which is the second commonest tumour. Second, skin tumours, except for melanomas, are excluded. Otherwise the book offers comprehensive coverage of tumours both benign and malignant, with important and useful information on clinical and radiological diagnosis (including ultrasound and MRI). Advances in MRI have helped not only in diagnosis but also in follow-up to detect recurrences and extensions. For malignant tumours the authors emphasize the need for investigation and treatment in specialist centres where hand surgeons, pathologists, oncologists and radiologists work as a team. Peripheral nerve sheath tumours and vascular tumours, which can be difficult to diagnose and manage, are well discussed, and an excellent section on soft tissue tumours ends with a chapter describing the 25-year experience of the Cooperative Osteosarcoma Study Group. All the chapters are well referenced.

Many kinds of surgeon—general, orthopaedic, plastic, neuro—will value the advice provided here on diagnosis and management. Trainee and specialist hand surgeons will find it particularly useful.
Lactic acidosis and diffuse histiocytic lymphoma (DHL)
Authors: Uri Mintz, Donald L. Sweet, Jacob D. Bitran, John E. Ultmann
Journal: American Journal of Hematology (1978)

Abstract Four patients with advanced diffuse histiocytic lymphoma who developed lactic acidosis are described. All four patients demonstrated disturbed liver function tests. In two of the patients, the lactic acidosis was unresponsive to treatment. The third patient responded successfully to the early initiation of combination chemotherapy with achievement of a clinical remission and correction of the lactic acidosis. The fourth patient responded to the initiation of chemotherapy with abatement of his lactic acidosis, but expired probably as the result of a pulmonary embolus. It seems likely that extensive hepatic infiltration may be one of the factors contributing to lactic acidosis in patients with diffuse histiocytic lymphoma. The early initiation of antineoplastic therapy may be important in the mangement of patients with histiocytic lymphoma and lactic acidosis.
Plague! The Shocking Story of a Dread Disease in America Today
Authors: Lester S. King
Journal: JAMA (1978)

The author has written an anecdotal account of the plague, designed for the layman but holding considerable interest for physicians. He recounts some details of the great epidemics of the past and offers information on pathogenesis, clinical course, and epidemiology. In journalistic style he describes recent outbreaks, both epidemic and sporadic. A surprising number of cases have occurred in the United States, and apparently the stage is set for further outbreaks. For any but the layman, the value of the book is considerably impaired through the absence of references. The author, after listing 17 good standard works that range from Boccaccio to Burnet, indicates that nearly 700 other references were used, including newspaper accounts and magazine articles, as well as scientific publications, but he does not list these. The principal sources for each chapter could easily have been inserted in a short appendix. As it is, however, the occasional purple
Abstract P6-12-15: Preclinical testing of a novel platelet derived growth factor receptor alpha (PDGFRa) inhibitor in inflammatory breast cancer
Authors: M Joglekar, S Van Laere, P Vermeulen, L Dirix, M Carter, A Rhamchandran, KL van Golen
Journal: Cancer Research (2013)

Abstract Inflammatory breast cancer (IBC) is the most lethal form of locally advanced breast cancer and carries a guarded prognosis. IBC presents with a “lumpless” primary tumor, which rapidly infiltrates and forms tumor emboli within the dermal lymphatic vessels of the skin overlying the breast. It is clear from the recent research advancements that IBC is a unique entity, not only in its clinical presentation, disease progression and response to therapy but also in its molecular expression profile. Therefore, it is essential to carry out molecular expression studies in IBC compared to non-IBC as well as to pursue these differences to study their effects on IBC phenotype. Our laboratory has demonstrated that the platelet derived growth factor receptor alpha (PDGFRa) is significantly over expressed in IBC patient samples (between 15-36%) compared to non-IBC patient samples. Using multiple approaches we demonstrate the PDGFRα activation signature in IBC patient samples and cell lines. Our data demonstrates that PDGFRα is constitutively active and localized in the cytoplasm of IBC cells. Although the receptor is intracellular, PDGFRα signaling remains intact. Thus, PDGFRα is an attractive target for therapy. Here we show that a novel PDGFR inhibitor, crenolanib, which specifically targets active PDGFR, is able to significantly inhibit IBC tumor growth and progression. In nude mice, 200 mm3 orthotopic IBC tumors did not increase in size when the mice were treated with crenolanib. In contrast, mice treated with vehicle control demonstrated a 4-fold increase in tumor growth over the 2-week course of the experiment. In addition, by using a novel in vitro IBC emboli growth model, we demonstrate that crenolanib prevents IBC tumor emboli formation and acts to sensitize IBC cells to chemotherapeutic agents. We were able to achieve a similar level of IBC cell killing with a 10-fold lower dose of chemotherapeutic agents compared to the agents by themselves. Together, these data demonstrate that PDGFRα is a viable target in IBC patients and that crenolanib is a potent and effective therapeutic agent against IBC cells. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-15.
A Hypoxia-Driven Vascular Endothelial Growth Factor/Flt1 Autocrine Loop Interacts with Hypoxia-Inducible Factor-1α through Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase 1/2 Pathway in Neuroblastoma
Authors: Bikul Das, Herman Yeger, Rika Tsuchida, Risa Torkin, Matthew F.W. Gee, Paul S. Thorner, Masabumi Shibuya, David Malkin, Sylvain Baruchel
Journal: Cancer Research (2005)

Abstract Flt1, an “fms-like tyrosine kinase” receptor, has been suggested to play an active role in vascular endothelial growth factor (VEGF)–mediated autocrine signaling of tumor growth and angiogenesis. Here, we used a neuroblastoma model to investigate the role of VEGF/Flt1 signaling in hypoxia-mediated tumor cell survival, drug resistance, and in vivo angiogenesis. SK-N-BE(2), a highly malignant neuroblastoma cell line resistant to hypoxia-induced apoptosis expresses active Flt1 but lacks VEGFR2 expression. We found that 24-hour hypoxia (&amp;lt;0.1% O2) alone (no serum deprivation) showed sustained activation of extracellular signal-regulated kinase 1/2 (ERK1/2) associated with bcl-2 up-regulation and resistance to etoposide-induced (5 μmol/L) apoptosis. Treatment with anti-VEGF and anti-Flt1 antibodies inhibited ERK1/2 activation, down-regulated bcl-2, and reversed the hypoxia-mediated drug resistance to etoposide. Similar results were obtained with U0126 and ursolic acid, specific and nonspecific inhibitors of ERK1/2, respectively. We confirmed the protective role of Flt1 receptor by small interfering RNA knockout and Flt1 overexpression studies. Subsequently, we found that inhibition of VEGF/Flt1 autocrine signaling led to reduced hypoxia-inducible factor-1α (HIF-1α) phosphorylation. Furthermore, the reduced phosphorylation was associated with down-regulation of basic fibroblast growth factor, a downstream target of the HIF-1α and VEGF pathways. Our findings suggested an expanded autocrine loop between VEGF/Flt1 signaling and HIF-1α. We investigated the angiogenic activity of the loop in an in vivo Matrigel plug assay. The hypoxia-treated conditioned medium induced a strong angiogenic response, as well as the cooption of surrounding vessels into the plugs; ursolic acid inhibited the angiogenesis process. We also found that three other Flt1-expressing neuroblastoma cell lines show hypoxia-mediated drug resistance to etoposide, melphalan, doxorubicin, and cyclophosphamide. Taken together, we conclude that a hypoxia-driven VEGF/Flt1 autocrine loop interacts with HIF-1α through a mitogen-activated protein kinase/ERK1/2 pathway in neuroblastoma. The interaction, in the form of an autocrine loop, is required for the hypoxia-driven cell survival, drug resistance, and angiogenesis in neuroblastoma.
200 CODING MICROSATELLITE INSTABILITY AFFECTING THE GENES AND IN A LYNCH-SYNDROME ASSOCIATED HEPATOCELLULAR CARCINOMA
Authors: M. Casper, M. Kloor, M. von Knebel-Doeberitz, R.M. Bohle, J. Raedle, F. Lammert, V. Zimmer
Journal: Journal of Hepatology (2011)
Dissociation of allergen-specific IgE and IgA responses in sera and tears of pollen-allergic patients: A study performed with purified recombinant pollen allergens
Authors: Rousan Aghayan-Ugurluoglu, Tanja Ball, Susanne Vrtala, Christian Schweiger, Dietrich Kraft, Rudolf Valenta
Journal: Journal of Allergy and Clinical Immunology (2000)