tbuckley/cabot-search huggingface dataset:
Radiotherapeutic management of isolated local-regional recurrence following mastectomy.
Authors: J Chen, X Guo, Z Pan, Y Feng, G Jiang
Journal: Cancer Research (2009)

Abstract Abstract #5135 Background: Postmastectomy isolated local-regional recurrence(ILRR) remains a therapeutic challenge. This retrospective study aims to evaluate the role of radiotherapy(RT) in these patients and to analyze factors that influence local-regional control and survival.&amp;#x2028; Methods: 255 pts with chest-wall(CW) and/or regional nodes recurrence(supraclavicular SC, axillary AXI and internal mammary nodes IMN) as first failure and received RT during 1990 and 2005 were analyzed, included 109 CW recurrence only, 114 regional nodes only and 32 pts with both, resulted in 304 recurrent sites. The median dose was 60Gy(47-74). Systemic treatment was give to 190 pts, including chemotherapy in 171, endocrine therapy(ET) in 69, and both in 41 pts.&amp;#x2028; Results: The median disease-free interval(DFI) was 22 mo(2-260 mo), which were 37 and 17 mo in pts with positive hormonal receptor (HR) and negative HR respectively. Median follow-up was 45 mo (9 mo -15.5 yrs). The 2, 5 and 8-yr overall survival rate was 86.4%, 56.5% and 35% respectively. Median survival time after recurrence was 79 mo. The 2, 5 and 8-yr local control rate was 56.1%, 36.3% and 27.6% respectively. 79 second recurrence in the initial recurrent region and 83 subsequent recurrence in other local-regional sites were found.&amp;#x2028; &amp;#x2028; CW is the most common site of second recurrence. Multivariate analysis showed that no CW involvement, non-diffuse recurrence and radiation to the entire recurrent region were independent prognostic factors on local control of initial recurrent sites. ET proved to be the only independent prognostic factors on subsequent recurrence in other sites. In pts with CW recurrence, small field(67 pts) resulted in significantly lower 5-yrs local control compared to entire CW irradiation(74 pts) (33.6% vs 55.6%, p=0.023). Cox regression model found that DFI≥1yr, positive HR, solitary CW or non-supraclavicular nodal recurrence were independent favorable prognostic factors on overall survival .&amp;#x2028; Conclusions: RT is an effective approach for ILRR after mastectomy. Radiation fields should cover the entire recurrent region. Elective irradiation to the CW in pts with nodal recurrence is recommended. Prognostic Index based on the positive multivariate analysis could be established as to stratify different prognostic sub-groups. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5135.
Effects of Training and Detraining on the Distribution of Cholesterol, Triglyceride, and Nitrogen in Tissues of Albino Rats
Authors: EDWARD W. WATT, MERLE L. FOSS, WALTER D. BLOCK
Journal: Circulation Research (1972)

The effects of standardized exercise training and detraining on the content of cholesterol, triglyceride, and nitrogen in blood, myocardium, skeletal muscle, and epididymal fat of rats were studied. Forty-eight 90-day-old male rats were randomly assigned to four groups (two control groups, one trained group, and one trained and detrained group). Trained rats were subjected to 8 weeks of moderate running in motor-driven wheels; detraining was effected by discontinuing the running program for 8 weeks. Rats were provided a standard diet and water ad libitum. Trained rats displayed lower body weights and resting bradycardia. Training lowered ( P &lt;0.01) serum cholesterol, serum triglyceride, and adipose triglyceride levels but had no effect on these lipids in heart or skeletal muscle. These lowered lipid levels persisted after 8 weeks of detraining even though body weight was regained rapidly. Total nitrogen content was higher ( P &lt;0.01) in myocardial and triceps muscles of both trained and trained-detrained rats. Heart cholesterol and triglyceride levels were unchanged by detraining, but skeletal muscle cholesterol content was lowered. The results indicate that the changes in lipid content associated with training and detraining are tissue specific: reduction occurred in some tissues (serum and adipose tissue), although the lipid content of others (skeletal and heart muscle) was independent of training status, body weight, or circulating lipid levels.
Reduced TH1/TH17 CD4 T-cell numbers are associated with impaired purified protein derivative–specific cytokine responses in patients with HIV-1 infection
Authors: Sally Clark, Emma Page, Tom Ford, Rebecca Metcalf, Anton Pozniak, Mark Nelson, Donald C. Henderson, David Asboe, Frances Gotch, Brian G. Gazzard, Peter Kelleher
Journal: Journal of Allergy and Clinical Immunology (2011)
The Red Cell: An Account of Its Chemical Physiology and Pathology
Authors: Joseph S. Burkle
Journal: JAMA (1962)

This monograph on the red blood cell is a most informative volume for clinicians and investigators interested in the basic aspects of the red blood cell. Written in a clear style, this book is a critical review of the tremendous advances that have been made in our knowledge of red blood cell physiology and hematology. Outstanding are the discussions of metabolism and molecular structures. All aspects that have been covered are well referenced. It was somewhat disappointing to find a minimal amount of material on low-temperature storage. Compensating for this is a jewel of a chapter on the "Red cells of different species," which tabulates neatly many facts that basic workers require in their animal work.
A Prospective Study of Chronic Lung Disease in Cotton Textile Workers
Authors: GERALD J. BECK
Journal: Annals of Internal Medicine (1982)

A cohort of both active and retired older cotton textile workers was examined prospectively over a 6-year period to establish the nature and extent of chronic lung disease. Respiratory symptoms and lung function were studied in these workers and in a group of similarly aged controls. The cotton textile workers had higher prevalence and attack rates of respiratory symptoms than did controls even with smoking habits taken into account. Chronic bronchitis developed in 16% of all cotton textile workers compared to 1% of controls over the follow-up period (p < 0.001). The cotton workers suffered a larger loss of lung function over 6 years than did controls. Male workers lost 42 mL/yr of forced expiratory volume in 1 second, although male controls lost only 25 mL/yr (p = 0.001). Similar differences were seen in women, and in both men and women who were nonsmokers. Retired cotton textile workers had more symptoms and disability than active workers. We conclude that chronic lung disease is not only irreversible but may progress even after exposure to cotton dust has ended.
Transplantation of an alginate–matrigel matrix containing isolated ovarian cells: First step in developing a biodegradable scaffold to transplant isolated preantral follicles and ovarian cells
Authors: Julie Vanacker, Valérie Luyckx, Marie-Madeleine Dolmans, Anne Des Rieux, Jonathan Jaeger, Anne Van Langendonckt, Jacques Donnez, Christiani A. Amorim
Journal: Biomaterials (2012)
Whole-Exome Sequencing Reveals Frequent Genetic Alterations in <i>BAP1</i>, <i>NF2</i>, <i>CDKN2A</i>, and <i>CUL1</i> in Malignant Pleural Mesothelioma
Authors: Guangwu Guo, Juliann Chmielecki, Chandra Goparaju, Adriana Heguy, Igor Dolgalev, Michele Carbone, Sara Seepo, Matthew Meyerson, Harvey I. Pass
Journal: Cancer Research (2014)

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm associated with asbestos exposure. Although previous studies based on candidate gene approaches have identified important common somatic mutations in MPM, these studies have focused on small sets of genes and have provided a limited view of the genetic alterations underlying this disease. Here, we performed whole-exome sequencing on DNA from 22 MPMs and matched blood samples, and identified 517 somatic mutations across 490 mutated genes. Integrative analysis of mutations and somatic copy-number alterations revealed frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1. Our study presents the first unbiased view of the genomic basis of MPM.
THE TOPOGRAPHIC DIAGNOSIS OF SUBTENTORIAL BRAIN TUMORS
Authors: HERMAN H. HOPPE
Journal: JAMA (1910)

<h3>TOPOGRAPHIC DIAGNOSIS</h3> The question as to whether or not we shall operate for tumors in this region, and if we operate, whether the operation shall be radical or palliative, can be decided only by an accurate topographic diagnosis. The subject of differential topographic diagnosis is therefore of prime importance. Surgical intervention is dangerous, or not, in the cerebellar region in direct ratio to the amount of exploration, handling and bruising to which the cerebellum is subjected. Moreover, if we know, from the location of the growth, that the chief disturbance produced is by an internal hydrocephalus, as in Case 1, the nature of the surgical interference will be different from that which is indicated if the growth itself, by local pressure, is threatening the life of the patient. More accurate topographic diagnosis will not
Hypomethylating Agents and Other Novel Strategies in Myelodysplastic Syndromes
Authors: Guillermo Garcia-Manero, Pierre Fenaux
Journal: Journal of Clinical Oncology (2011)

Over the last decade, treatment approaches for patients with myelodysplastic syndromes (MDS) have improved significantly. Treatment of MDS is tailored to the specific risk characteristics of the patient. In general, patients are divided into lower- and higher-risk categories. Without therapy, prognosis of patients with higher-risk MDS is poor, and treatments should be directed to improve survival. Prognosis of patients with lower-risk MDS is more heterogeneous, and therapies are usually directed to minimize transfusion needs and potentially to alter the natural course of the disease. Treatment options for patients with higher-risk MDS include hypomethylating agents (azacitidine and decitabine), intensive chemotherapy (ICT), and allogeneic stem-cell transplantation (alloSCT). The use of the hypomethylating agents has transformed the approach to this patient population, in particular older individuals, for whom ICT and alloSCT are not an option. In lower-risk MDS, treatment strategies are used sequentially and usually include observation in patients with low risk and no transfusion dependency, growth factors, and lenalidomide for patients with alteration of chromosome 5 and anemia. The use of hypomethylating agents is less understood in this group of patients. AlloSCT is usually reserved for patients with lower-risk MDS closer to the time of transformation. In this short review, we discuss treatment alternatives for patients with MDS and delineate some of the ongoing challenges, including the development of better front-line strategies for patients with higher-risk disease, the concept of altering the natural course of the disease in lower-risk MDS, and the development of new treatment approaches for patients who do not benefit from hypomethylating agents.
Intrathecal Injection of Naked Plasmid DNA Provides Long-term Expression of Secreted Proteins
Authors: Travis S Hughes, Stephen J Langer, Kirk W Johnson, Raymond A Chavez, Linda R Watkins, Erin D Milligan, Leslie A Leinwand
Journal: Molecular Therapy (2008)

Therapeutic benefit has been reported to result from intrathecal (i.t.) injection of transgene vectors, including naked DNA. However, most studies using naked DNA have measured only the transgene expression of intracellular proteins. Here we demonstrate that i.t. injection of naked DNA can result in long-term expression of secreted proteins. Plasmids expressing either secreted alkaline phosphatase (SEAP) or human interleukin-10 (hIL-10) were injected into the i.t. space in rats, and transgene products were repeatedly measured in the cerebrospinal fluid (CSF). Both SEAP and hIL-10 were maximal at 1 and 2 days after the injection and still detectable at 4 months. The utilization of a plasmid having two features that are hypothesized to increase gene expression (matrix attachment regions (MARs) and lack of CpG dinucleotides) resulted in a significant increase in gene expression. Reinjection of SEAP or hIL-10 plasmids after 4 months significantly increased protein levels at 1 and 14 days after the reinjection. SEAP was uniformly distributed between the DNA delivery site (approximately vertebral level T13) and the lumbar puncture site (L5/L6 inter-vertebral space), was reduced at the cisterna magna, and was detectable, though at much lower levels, in serum. These data suggest that naked DNA has the potential to be used as a therapeutic tool for applications that require long-term release of transgenes into the CSF.
Fungal Splenic Abscesses in the Immunosuppressed Patient
Authors: TONY E. VASQUEZ, DAVID G. EVANS, H SCHIFFMAN, WILLIAM L. ASHBURN
Journal: Clinical Nuclear Medicine (1987)

A patient with fungal splenic abscesses is presented in whom multiple noninvasive diagnostic imaging modalities were available for correlation. Of the five imaging modalities, three (Gallium-67, ultrasound and computed tomography) were diagnostically useful, while two (liver-spleen scan and ln-111 white blood cell scan) were not as useful. This case also stresses the use of repeated studies correlating with clinical impressions to obtain an accurate diagnosis in a potentially lifethreatening condition such as splenic abscess.
The Intraepithelial Lesion: More Problems and Few Data-Reply
Authors: D. K. Ohrt
Journal: JAMA (1990)

<h3>In Reply. —</h3> Dr Austin correctly points out that there is a literature that supports aggressive clinical follow-up of patients with any form of cytological atypia. He neglects to add that there also exists a substantial literature that supports conservative clinical follow-up for this same group of patients.<sup>1-5</sup>In fact, some of the articles he has cited support that approach. The question of whether to follow up cytological findings of atypia or low-grade squamous intraepithelial lesion conservatively or aggressively has thus long been recognized and clearly remains unresolved. The only unanimity among gynecologists and pathologists on this issue seems to be that some type of further evaluation, either cytological, colposcopic, or both, is indeed mandatory. The key unresolved question is whether colposcopic follow-up yields better long-term outcomes (ie, preventing and detecting invasive cancer) than does cytological follow-up. As previously stated, this question has not been addressed scientifically. No conclusive
Evidence for ozone-induced small-airway dysfunction: lack of menstrual-cycle and gender effects.
Authors: G G Weinmann, M Weidenbach-Gerbase, W M Foster, H Zacur, R Frank
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Recently, we analyzed FEF25-75 isovolumetrically to assess the acute effects of ozone (O3) on small-airway function: the reduction in isovolumetric (isoV) FEF25-75 at end exposure progressed during the next 25 min even as FVC was recovering. To evaluate this effect over a longer period, we measured isovolumetric FEFs, helium-oxygen (He-O2) volume of isoflow (VisoV), the multiple breath nitrogen washout (MBNW) curve, FRC, and RV in 24 subjects 24 h after a 130-min exposure to filtered air (FA) and O3 (0.35 ppm). Men and women were studied to test for gender-based differences in response, after first determining that menstrual-cycle phase did not itself influence response. Isovolumetric FEF25-75, Vmax50, and Vmax75 were reduced about equally at 25 min after O3 exposure (p < or = 0.02) and showed no recovery at 24 h. FVC and FEV1, although still depressed after 24 h (p < 0.05), showed substantial recovery (p < 0.01). FRC, RV, and VisoV showed no effect of O3 exposure. No gender differences in O3 responsiveness were found. In summary, O3-induced reductions in isovolumetric flow rates, suggestive of small-airway dysfunction, may persist for 24 h following acute exposure to O3, a time-course consistent with inflammation.
STUDIES ON PHENYLKETONURIA. I. RESTRICTED PHENYLALANINE INTAKE IN PHENYLKETONURIA 1
Authors: Marvin D. Armstrong, Frank H. Tyler
Journal: Journal of Clinical Investigation (1955)

The relationship between the biochemical defect in the.hereditary condition, phenylketonuria (phenylpyruvic oligophrenia), and the accompanying mental defect is at the present time obscure. The work of F6lling (1) and Jervis (2, 3) has shown that the inheritance of the condition appears to be controlled by a single autosomal recessive gene. A series of investigations by Jervis and his collaborators (4-1 ) has demonstrated that the biochemical defect lies in a failure of the affected individuals to oxidize phenylalanine to tyrosine in the normal fashion. The major abnormal metabolites known to occur in this condition can arise as a logical consequence of the accumulation of large amounts of phenylalanine and the channelling of this phenylalanine into abnormal pathways. These metabolites are phenylalanine itself (8), phenylpyruvic acid (8), phenyllactic acid (8), and phenylacetylglutamine (12). Abnormally high levels of phenylalanine are found in serum (20 to 60 mg. per 100 ml.) and cerebrospinal fluid (6 to 8 mg. per 100 ml.) (9) and phenylpyruvic acid has been demonstrated in the serum of affected individuals (10). Recently it has been found that lesser amounts of other abnormal metabolites are excreted. These include o-hydroxyphenylacetic acid (13, 14) and products derived from tyrosine (13, 15) and tryptophan (15, 16). The manner in which these substances arise will be considered in later communications.
The IgE repertoire in PBMCs of atopic patients is characterized by individual rearrangements without variable region of the heavy immunoglobulin chain bias
Authors: Annick Lim, Stephan Luderschmidt, Anke Weidinger, Christina Schnopp, Johannes Ring, Rüdiger Hein, Markus Ollert, Martin Mempel
Journal: Journal of Allergy and Clinical Immunology (2007)
Ebstein's Malformation of the Tricuspid Valve
Authors: C. WALTON LILLEHEI, PAUL G. GANNON
Journal: Circulation (1965)

Two cases of complete correction of Ebstein's malformation are presented. The deformed tricuspid valve was excised. A ball-valve prosthesis was anchored at the true annulus. This procedure removes the obstruction to right ventricular outflow, eliminates tricuspid insufficiency, increases right ventricular diastolic capacity, and improves the pumping action of the right ventricle by increasing the size and effectiveness of the pump chamber. Preoperatively, both patients were cyanotic because of large right-to-left shunts at the atrial level. No attempt was made to close the associated atrial septal defect in our first case. This patient continued to shunt right-to-left postoperatively but expired early in the postoperative period as a result of right-heart failure. A flap-valve type closure of the large associated atrial septal defect in the second patient with Ebstein's malformation permitted right-to-left shunting until the right ventricle became competent to pump the entire venous return to the lungs. About two weeks after surgery the right-to-left shunting ceased in this patient. Both patients developed complete heart block during the tricuspid valve prosthesis insertion. This complication was compensated for by a myocardial electrode and external pacemaker in the early postoperative interval. The second patient was discharged in an asymptomatic condition following insertion of an implantable pacemaker. A possible method for avoiding heart block in these cases in the future is discussed.
Abstract IA18: Early but promising data: PD-1 inhibitors in non-small cell lung cancer.
Authors: Edward B. Garon, Brian R. Wolf, Deborah JL Wong, Jonathan W. Goldman
Journal: Clinical Cancer Research (2014)

Abstract Blockade of the programmed death (PD-1) checkpoint has emerged as a promising approach for immunotherapies in the treatment of non-small cell lung cancer (NSCLC). Immune checkpoints, such as PD-1, an inhibitory T-cell immunoreceptor, and the receptor's ligands, PD-L1 and PD-L2, assist in hindering autoimmunity and protecting peripheral tissues to minimize damage (1). However, in cancers, the interaction between PD-1 and its ligands also can result in the promotion of an immunosuppressive tumor microenvironment (1). Several agents targeting PD-1 are currently undergoing clinical development. Clinical trials of anti-PD-1 antibodies nivolumab (BMS-936558) and MK-3475 have produced encouraging results in non-small cell lung cancer patients with regards to objective response rates (ORR) and progression free survival (PFS) (2,3). In a pretreated advanced NSCLC population, nivolumab produced durable responses, particularly at 3 and 10 mg/kg doses (2). For 38 previously-treated NSCLC patients, MK-3475, administered at 10 mg/kg every three weeks, led to an ORR of 24 percent based on irRC (21 percent based on RECIST 1.1) (3). Median overall survival was 51 weeks with a PFS, which had not been reached at a time when the minimum PFS would be 62 weeks among the responders (3). ORR was 67% in patients with tumors having PD-L1 expression above a cutpoint versus 4% in those below the cutpoint (3). Based on the favorable response rates relative to historical controls, and the durability of responses in clinical trials, the development of PD-1 inhibitors in lung cancer is proceeding rapidly. Future trials utilizing anti PD-1 antibodies will explore further biomarkers, and combination with other therapies. Citation Format: Edward B. Garon, Brian R. Wolf, Deborah JL Wong, Jonathan W. Goldman. Early but promising data: PD-1 inhibitors in non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA18.
STUDIES ON NORMAL AND LEUKEMIC LEUKOCYTES. IV. TETRAHYDROFOLATE-DEPENDENT ENZYME SYSTEMS AND DIHYDROFOLIC REDUCTASE*
Authors: J. R. Bertino, Robert Silber, M. Freeman, A. Alenty, M. Albrecht, Beverly W. Gabrio, F. M. Huennekens
Journal: Journal of Clinical Investigation (1963)

A number of investigations (3-6) have been concerned with biochemical characteristics of normal and leukemic leukocytes with special reference to enzymatic reactions that might represent potential targets for chemotherapeutic agents.Tetrahydrofolate-dependent enzyme systems provide a particularly promising area for this approach, since they mediate reactions in which 1-carbon units are incorporated into precursors of nucleic acids and proteins, namely, inosinate, thymidylate, methionine, histidine, and serine (7-9).Further support for this reasoning is provided by other experimental facts: a) the levels of folic acid and folinic acid are considerably higher in acute leukemia cells than in normal cells (10); b) the folic acid antagonists (aminopterin, amethopterin, and dichloroamethopterin) frequently produce transient remissions in patients with acute leukemia; and c) the rate of incorporation of C14formate and C14-formaldehyde into purines and into DNA-thymine is markedly increased in chronic myelocytic leukemic cells as compared with normal cells, and these processes are inhibited by aminopterin and amethopterin (11-13).In the present investigation several tetrahydrofolate-dependent enzymes and dihydrofolic re- ductase ( 14) have been studied in circulating hu- nman leukocytes.A comparison has been made of the level of these enzymes in normal cells and in
INTERLEUKIN-6, BUT NOT C-REACTIVE PROTEIN, IS ASSOCIATED WITH CHANGES IN SPECKLE TRACKING DERIVED LEFT VENTRICULAR PEAK SYSTOLIC STRAIN, INDEPENDENT OF OBESITY OVER A FIVE-YEAR FOLLOW-UP PERIOD: THE CARDIA STUDY
Authors: Mahadevan Rajaram, Anderson Armstrong, Satoru Kishi, Laura Colangelo, David Jacobs, Cora Lewis, Samuel Gidding, Stephen Sidney, Kiang Liu, Joao Lima
Journal: Journal of the American College of Cardiology (2013)