tbuckley/cabot-search huggingface dataset:
Molecular Breast Imaging as a Cost Effective Diagnostic Tool for Breast Cancer.
Authors: A. Larsen, J. Hughes, T. Frazier
Journal: Cancer Research (2009)

Abstract Introduction: Molecular breast imaging (MBI), also referred to as breast specific gamma imaging (BSGI), utilizes nuclear medicine imaging with technetium 99-sestamibi to demonstrate metabolic activity of breast tissue. A focused gamma camera is used to assist in detecting lesions concerning for malignancy based on abnormal radiotracer uptake. MBI is performed with the patient in a sitting position and requires less breast compression than mammography. MBI is safe for patients with implanted metallic devices and renal disease. Facility charge for MBI is approximately $600 vs. $2500 for magnetic resonance imaging (MRI).Methods: IRB approval was obtained prior to study initiation. Forty four (44) patients underwent MBI with technetium 99-sestamibi after mammography and or ultrasound detected abnormalities for which biopsy was recommended.Results: Forty four (44) women ranging in age from 28 to 82 (median age 52) were found to have abnormal mammogram and or ultrasound findings requiring image guided biopsy. Prior to biopsy, MBI was performed. Fifteen MBI's were interpreted as demonstrating areas concerning for malignancy. Nine of the 44 patients (20.5%) demonstrated malignancy on biopsy pathology. Eight of these nine patients had positive MBI findings concerning for malignancy (88.9%). The patient whose MBI did not demonstrate findings consistent with malignancy had two sites of DCIS. The positive predictive value of these results was 53.3% and the negative predictive value was 96.55%.Conclusions: MBI shows promise in evaluating patients with abnormal mammogram or ultrasound findings. MBI is available at a much lower cost than MRI ($600 vs. $2500), which would have resulted in savings of $83,600 in this study alone. MBI can be used in patients for whom MRI is not an option such as claustrophobic patients, patients with renal disease limiting use of gadolinium contrast and patients who for other reasons such as body habitus and implanted metallic devices are not candidates for MRI. Further studies evaluating MBI are warranted to determine what role it may play in providing additional diagnostic data about patients with abnormal mammograms or ultrasounds. The role of MBI in settings where breast MRI is not available, is not technically feasible or is not an option due to cost also warrants further evaluation. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5014.
Abstract 623: BIG3-PHB2 interaction is a key therapeutic target in luminal-type of breast cancer
Authors: Toyomasa Katagiri, Tesuro Yoshimaru, Masato Komatsu, Taisuke Matsuo
Journal: Cancer Research (2014)

Abstract More than 70% of primary breast tumors are estrogen receptor alpha (ERα)-positive, and the interactions between estrogen (E2) and ERα dramatically enhance the proliferative and metastatic activity of breast tumor cells. The selective estrogen receptor modulator tamoxifen directly inhibits E2 and ERα interactions and is a standard treatment offered to patients with ERα-positive breast cancer. The acquisition of endocrine resistance is a common obstacle in endocrine therapy for ERα-positive breast tumors. Therefore, identifying the factors and pathways responsible for resistance and defining ways to overcome it represent important therapeutic challenges in breast cancer research. Prohibitin 2 (PHB2) is known to function as a co-repressor of ERα because it regulates ERα transcriptional activity via its direct binding to ERα. However, it remains unclear how endogenous PHB2 is inactivated in ERα-positive breast cancer cells, despite its abundant expression and the lack of genomic mutations or methylations in breast cancer clinical specimens or cell lines. Here we report that brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) protein interacts PP1α, and dephosphorylates the E2-dependent phosphorylation of PHB2, which is indispensable for its tumor suppressive ability, thereby causing an apparent “loss-of-function” of PHB2 protein, resulting in the constitutive activation of ERα signaling pathways. These findings demonstrate for the first time the novel mechanism for the inactivation of tumor suppressor protein. From a therapeutic perspective, intrinsic PHB2 released from BIG3 by the cell-permeable peptide inhibitor directly binds to both nuclear- and membrane-associated ERα, which leads to the inhibition of multiple ERα-signaling pathways, and the growth of ERα-positive breast cancer cells both in vitro and in vivo. More importantly, this peptide inhibitor treatment suppressed tamoxifen resistance and enhanced tamoxifen responsiveness in ERα-positive breast cancer cells. These findings mark the first step toward uncovering a new E2/ ERα signaling network in breast cancer and shed light on novel therapeutic strategies utilizing PHB2 protein functions for E2/ ERα-positive breast cancer. Citation Format: Toyomasa Katagiri, Tesuro Yoshimaru, Masato Komatsu, Taisuke Matsuo. BIG3-PHB2 interaction is a key therapeutic target in luminal-type of breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 623. doi:10.1158/1538-7445.AM2014-623
Points from letters: Senile dementia
Authors: R Piper
Journal: BMJ (1978)

Most immune responses follow Burnet’s rule in that Ag recruits specific lymphocytes from a large repertoire and induces them to proliferate and differentiate into effector cells. However, the phenomenon of “original antigenic sin” stands out as a paradox to Burnet’s rule of B cell engagement. Humans, upon infection with a novel influenza strain, produce Abs against older viral strains at the expense of responses to novel, protective antigenic determinants. This exacerbates the severity of the current infection. This blind spot of the immune system and the redirection of responses to the “original Ag” rather than to novel epitopes were described fifty years ago. Recent reports have questioned the existence of this phenomenon. Hence, we revisited this issue to determine the extent to which original antigenic sin is induced by variant influenza viruses. Using two related strains of influenza A virus, we show that original antigenic sin leads to a significant decrease in development of protective immunity and recall responses to the second virus. In addition, we show that sequential infection of mice with two live influenza virus strains leads to almost exclusive Ab responses to the first viral strain, suggesting that original antigenic sin could be a potential strategy by which variant influenza viruses subvert the immune system.
Acute myocardial infarction as a complication of diabetic neuropathy
Authors: C. Almog
Journal: JAMA (1978)

ALTHOUGH autonomic neuropathy is common in diabetes, clinically troublesome orthostatic hypotension caused by the involvement of the vasomotor system is not frequently observed. Distinctly unusual is postural hypotension severe enough to precipitate a myocardial infarction, as in our patient's case.  Report of a Case  A 60-year-old woman with mild diabetes treated with tolbutamide was admitted to the hospital for recurrent episodes of loss of consciousness and disturbances in micturition. She complained of dizziness while sitting. Her pulse rate was 84 beats per minute, and her blood pressure was 140/80 mm Hg, supine. The ECG was normal. The abdomen was distended, and the sphincter ani was atonic. She had diabetic retinopathy, and her ankle and patellar reflexes were absent.  On the day after admission, the patient lost consciousness as her blood pressure dropped precipitously when she stood up. She regained consciousness promptly on lying down, but complained of a pressure sensation
Parenchymal and nonparenchymal uptake of technetium 99m, indium-111, and iodine-125 low-density lipoprotein in the normal and estradiol-stimulated rat liver: Tracer validation for quantitative low-density lipoprotein scintigraphy
Authors: T LEITHA
Journal: Hepatology (1995)

This study quantifies the parenchymal and nonparenchymal uptake of technetium-99m (99mTc)- and indium111 (111In)-low-density lipoprotein (LDL) in different states of hepatic LDL-receptor activity to validate quantitative LDL scintigraphy. Iodine-125 (125I)-LDL was used as reference tracer. Four Sprague-Dawley rats with 17-alpha-ethinyl estradiol (EE)-stimulated LDL-receptor activity and five controls received all three tracers simultaneously 90 minutes before collagenase liver perfusion and metrizamide gradient cell separation. Total liver uptake of 99mTc-, 111In-, and 125I-LDL was 1.8 ± 1.0, 1.6 ± 0.8, and 0.2 ± 0.2% injected dose/g organ weight, respectively. The contribution of nonparenchymal cells to total hepatic tracer uptake was 5.4 ± 4.7%, 11.6 ± 10.3%, and 9.6 ± 7.6% in controls. Estradiol treatment increased total liver uptake to 2.4 ± 0.5,2.0 ± 0.2, and 0.5 ± 0.3% injected dose/g and reduced nonparenchymal cell contribution to 2.3 ± 2.6%, 4.2 ± 4.8%, and 2.6 ± 2.9%, respectively. Dual-isotope scintigraphy in EE-treated and control rats confirmed these data, with a lower total hepatic uptake of 111In-LDL in comparison with 99mTcLDL but a comparative degree of increase by EE treatment. Both behave quantitatively comparable as residualizing tracers, yet 99mTc-LDL shows a higher affinity to the LDL receptor pathway of parenchymal cells. However, the nonspecific uptake of both tracers can be neglected for quantitative LDL scintigraphy, and external imaging of hepatic tracer uptake primarily reflects LDLreceptor activity of parenchymal cells
Antibacterial activity of human neutrophil defensins in experimental infections in mice is accompanied by increased leukocyte accumulation.
Authors: M M Welling, P S Hiemstra, M T van den Barselaar, A Paulusma-Annema, P H Nibbering, E K Pauwels, W Calame
Journal: Journal of Clinical Investigation (1998)

Neutrophil defensins (or human neutrophil peptides-HNP) are major constituents of the azurophilic granules of human neutrophils and have been shown to display broad-spectrum antimicrobial activity. Other activities of these defensins, which are released from stimulated neutrophils, include cytotoxic, stimulatory, and chemotactic activities toward a variety of target cells. We studied the potential use of HNP-1 for antibacterial therapy of experimental bacterial infections in mice. In experimental peritoneal Klebsiella pneumoniae infections in mice, HNP-1 injection was shown to markedly reduce bacterial numbers in the infected peritoneal cavity 24 h after infection. This antibacterial effect was found to be associated with an increased influx of macrophages, granulocytes, and lymphocytes into the peritoneal cavity. These leukocytes appeared to be a requirement for the antibacterial effect, since in leukocytopenic mice administration of HNP-1 did not display antibacterial activity. HNP-1 treatment also reduced bacterial numbers in experimental K. pneumoniae or Staphylococcus aureus thigh muscle infections. In this model, radiolabeled HNP-1 was found to accumulate at the site of infection, whereas most of the injected HNP-1 was rapidly removed from the circulation via renal excretion. These results demonstrate that neutrophil defensins display marked in vivo antibacterial activity in experimental infections in mice and that this activity appears to be mediated, at least in part, by local leukocyte accumulation.
ITMIG Consensus Statement on the Use of the WHO Histological Classification of Thymoma and Thymic Carcinoma: Refined Definitions, Histological Criteria, and Reporting
Authors: Alexander Marx, Philipp Ströbel, Sunil S. Badve, Lara Chalabreysse, John K.C. Chan, Gang Chen, Laurence de Leval, Frank Detterbeck, Nicolas Girard, Jim Huang, Michael O. Kurrer, Libero Lauriola, Mirella Marino, Yoshihiro Matsuno, Thierry Jo Molina, Kiyoshi Mukai, Andrew G. Nicholson, Daisuke Nonaka, Ralf Rieker, Juan Rosai, Enrico Ruffini, William D. Travis
Journal: Journal of Thoracic Oncology (2014)
Etiology and Pathogenesis of Acute Myocardial Infarction
Authors: Thomas Killip, JESSE E. EDWARDS
Journal: Circulation (1969)

From the pathological viewpoint, myocardial infarction is but one major consequence of coronary atherosclerosis. Among subjects with chronic occlusive coronary atherosclerosis, more common than death from acute myocardial infarction is death occurring acutely in the absence of infarction or acute coronary occlusion. Such negative anatomical evidence is supportive of the concept that myocardial ischemia commonly causes serious failure of the circulation through certain ventricular arrhythmias.
Pancytopenia Due to Mesantoin
Authors: Robert R. Davies, Charles Fisch, E. Paul Tischer
Journal: New England Journal of Medicine (1950)

SINCE the introduction of Mesantoin (3 methyl-5, 5-phenylethyl-hydantoin) as an anticonvulsant a number of cases of depression of bone marrow, thought to be due to this drug, have been reported.1 2 3 4 5 We wish to add another case of pancytopenia due to Mesantoin.Case ReportB. L. Z., a 28-year-old pharmacy student, was admitted to the hospital on August 3, 1948, complaining of multiple bruises, spontaneous nosebleeds, sore throat, chills and fever. In August, 1947, while in bed, he experienced an episode characterized by tonic and clonic movements of the body, arms and legs and subsequent mental confusion. This was diagnosed as . . .
Air Sampling for Legionella
Authors: Guthrie S. Birkhead
Journal: JAMA (1990)

<h3>To the Editor.—</h3> In the article by Breiman et al,<sup>1</sup>microbial air sampling was conducted to help establish the source of an outbreak of legionnaires' disease linked to shower use. This complements another article in which similar environmental sampling techniques identified an evaporative condenser as the source of<i>Legionella</i>infection.<sup>2</sup>We have used similar methods to demonstrate the association of three cases of legionnaires' disease and the use of a whirlpool-spa. Three cases of legionnaires' disease were reported to the New York State Department of Health in September 1989. All three patients were members of a 20-man golf team that had stayed at a Vermont resort hotel. The resort health club had two whirlpool-spas, only one of which was functional and was used by all three patients 3 days prior to the onset of illness. Two patients had greater than fourfold increases in<i>Legionella pneumophila</i>serogroup 1 (Lpl)
The E mu-myc transgenic mouse. A model for high-incidence spontaneous lymphoma and leukemia of early B cells.
Authors: A W Harris, C A Pinkert, M Crawford, W Y Langdon, R L Brinster, J M Adams
Journal: The Journal of Experimental Medicine (1988)

Mice transgenic for a c-myc gene driven by the IgH enhancer (E mu-myc) were shown to almost invariably develop lymphomas, 90% succumbing in the first 5 mo of life. The tumors typically presented as rapidly progressive lymphadenopathy with thymic involvement and were highly malignant by transplantation assay. Morphologically, they were lymphoblastic lymphomas, usually accompanied by lymphoid leukemia and granulocytosis, and were distinct from the tumors that arose much later in 37% of nontransgenic mice of the same (C57BL/6 x SJL)F2 genetic background. Cell-surface markers on 31 E mu-myc tumors identified 52% as pre-B lymphomas, 29% as mixed pre-B and B lymphomas, and 19% as B lymphomas. The tumors appeared to arise at random from a population of pre-B cells expanded by constitutive expression of the myc transgene. A majority of the animals initiated malignancy at the rate of 17% per week. The rate at which the cycling, benign pre-B cells spontaneously convert to malignancy was estimated to about 10(-10) per cell per generation. A transient leukocytosis identified in young E mu-myc mice was developed into a rapid assay for inheritance of the transgene.
Cost Consideration in the Clinical Guidance Documents of Physician Specialty Societies in the United States
Authors: Jennifer A. T. Schwartz, Steven D. Pearson
Journal: JAMA Internal Medicine (2013)

Despite increasing concerns regarding the cost of health care, the consideration of costs in the development of clinical guidance documents by physician specialty societies has received little analysis.To evaluate the approach to consideration of cost in publicly available clinical guidance documents and methodological statements produced between 2008 and 2012 by the 30 largest US physician specialty societies.Qualitative document review.Whether costs are considered in clinical guidance development, mechanism of cost consideration, and the way that cost issues were used in support of specific clinical practice recommendations.Methodological statements for clinical guidance documents indicated that 17 of 30 physician societies (57%) explicitly integrated costs, 4 (13%) implicitly considered costs, 3 (10%) intentionally excluded costs, and 6 (20%) made no mention. Of the 17 societies that explicitly integrated costs, 9 (53%) consistently used a formal system in which the strength of recommendation was influenced in part by costs, whereas 8 (47%) were inconsistent in their approach or failed to mention the exact mechanism for considering costs. Among the 138 specific recommendations in these guidance documents that included cost as part of the rationale, the most common form of recommendation (50 [36%]) encouraged the use of a specific medical service because of equal effectiveness and lower cost.Slightly more than half of the largest US physician societies explicitly consider costs in developing their clinical guidance documents; among these, approximately half use an explicit mechanism for integrating costs into the strength of recommendations. Many societies remain vague in their approach. Physician specialty societies should demonstrate greater transparency and rigor in their approach to cost consideration in documents meant to influence care decisions.
THE CAUSE OF MUSCULAR ATROPHY FOLLOWING NERVE SECTION
Authors: H. C. STEVENS
Journal: JAMA (1918)

The nervous system is held to exert a "trophic influence" over the tissues of the body.In proof of this alleged influence, it is pointed out that pathologic changes occur in many tissues as the result of injuries to nerves or to the spinal cord.The pathologic changes usually cited are herpes zoster, the Charcot
Antifibrotic effect of adipose stromalcells on chondrocytes from osteoarthritic patients
Authors: M Maumus, C Manferdini, K Toupet, J-A Peyrafitte, A Piacentini, E Gabusi, A Facchini, P Bourin, C Jorgensen, G Lisignoli, D Noël
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Purposes</h3> Osteoarthritis (OA) characterised by degeneration of articular cartilage is the most frequent rheumatic disease. Mesenchymal stem cells (MSC) isolated from bone marrow (MSC) or adipose tissues (ASC) secrete a large amount of factors with immunomodulatory, proliferative, antifibrotic or antiapoptotic properties. The possibility that these cells, through their trophic potential, may influence the course of chronic degenerative disorders and prevent cartilage degradation is promising for the treatment of OA. Indeed, the aim of our work was to evaluate the effects of ASC or MSC on OA chondrocyte phenotype. <h3>Methods</h3> OA ASC were isolated from intra-articular (Hoffa-ASC) or hip (hip ASC) subcutaneous adipose tissue and healthy ASC from subcutaneous abdominal depot (abdo-ASC). BM-MSC and chondrocytes were obtained from OA donors. ASC or MSC were co-incubated with chondrocytes cultured in monolayer during 7 days using cell culture inserts. Expression of collagens (Col) I, IIB, III, X, aggregan (Agg), link, Sox9, MMP13, alkaline phosphatase (AP) was quantified by RT-qPCR. Secreted factors were quantified by ELISA. Isotypic or anti-HGF antibodies (100 ng/ml) were added during the coculture. <h3>Results</h3> After 7 days of chondrocyte and abdo-ASC co-cultures, a stable expression of the markers specific for mature chondrocytes (Col IIB, Agg, link, Sox9) was observed, while expression of hypertrophic (MMP13, AP) and fibrotic (Col I and III) markers was significantly decreased. Compared to abdo-ASCs, Hoffa- and Hip-ASC reduced less efficiently the expression of hypertrophic/fibrotic markers and some markers of mature chondrocytes were decreased with Hip-ASC. OA MSC behaved as abdo-ASC maintaining a stable expression of chondrocyte markers and reducing hypertrophic/fibrotic markers (MMP13, Col I and III). Finally, factors known to be involved in fibrosis and matrix remodelling (HGF, TIMP-1 and -2, MMP-1 and -9, IL1-RA) were quantified in culture supernatants. The authors observed that HGF was not secreted by chondrocytes or ASC alone but its secretion was induced after co-culture. Importantly, addition of neutralising anti-HGF antibody reversed the antifibrotic effect of ASC whereas the hypertrophic markers were not modulated confirming the role of HGF on the inhibition of fibrosis. <h3>Conclusions</h3> SC from abdominal subcutaneous fat and MSC were the most efficient to reduce hypertrophy and dedifferentiation of articular chondrocytes. This effect was at least partly due to the induction of HGF secretion which is a known antifibrotic factor confirming the interest of using ASC in therapies of osteo-articular diseases.
BCR/ABL induces multiple abnormalities of cytoskeletal function.
Authors: R Salgia, J L Li, D S Ewaniuk, W Pear, E Pisick, S A Burky, T Ernst, M Sattler, L B Chen, J D Griffin
Journal: Journal of Clinical Investigation (1997)

The BCR/ABL oncogene causes human chronic myelogenous leukemia (CML), a myeloproliferative disease characterized by massive expansion of hematopoietic progenitor cells and cells of the granulocyte lineage. When transfected into murine hematopoietic cell lines, BCR/ABL causes cytokine-independence and enhances viability. There is also growing evidence that p210(BCR/ABL) affects cytoskeletal structure. p210(BCR/ABL) binds to actin, and several cytoskeletal proteins are tyrosine phosphorylated by this oncoprotein. Also, at least one aspect of cytoskeletal function is abnormal, in that the affinity of beta1 integrins for fibronectin is altered in CML cells. However, isolated changes in beta1 integrin function would be unlikely to explain the clinical phenotype of CML. We used time-lapse video microscopy to study cell motility and cell morphology on extracellular cell matrix protein-coated surfaces of a series of cell lines before and after transformation by BCR/ABL. BCR/ABL was associated with a striking increase in spontaneous motility, membrane ruffling, formation of long actin extensions (filopodia) and accelerated the rate of protrusion and retraction of pseudopodia on fibronectin-coated surfaces. Also, while untransformed cells were sessile for long periods, BCR/ABL-transformed cells exhibited persistent motility, except for brief periods during cell division. Using cell lines transformed by a temperature-sensitive mutant of BCR/ABL, these kinetic abnormalities of cytoskeletal function were shown to require BCR/ABL tyrosine kinase activity. Similar abnormalities of cytoskeletal function on fibronectin-coated surfaces were observed when hematopoietic progenitor cells purified by CD34 selection from patients with CML were compared with CD34 positive cells from normal individuals. Interestingly, alpha-interferon treatment was found to slowly revert the abnormal motility phenotype of BCR/ABL-transformed cells towards normal. The increase in spontaneous motility and other defects of cytoskeletal function described here will be useful biological markers of the functional effects of BCR/ABL in hematopoietic cells.
Limited urinary concentration and damaged tubules in rats with a syngeneic kidney graft
Authors: Mari Michimata, Weihua Wang, Sayuri Fujita, Haruo Mizutani, Keisei Fujimori, Susumu Satomi, Masahiro Ohta, Sadayoshi Ito, Tokihisa Kimura, Tsutomu Araki, Yutaka Imai, Mitsunobu Matsubara
Journal: Kidney International (2001)