tbuckley/cabot-search huggingface dataset:
STRUCTURAL CHANGES PRODUCED IN BROWN-PEARCE CARCINOMA CELLS BY MEANS OF A SPECIFIC ANTIBODY AND COMPLEMENT
Authors: Bernard Kalfayan, John G. Kidd
Journal: The Journal of Experimental Medicine (1953)

Structural changes were regularly observed in Brown-Pearce rabbit carcinoma cells that had been brought into contact, in the presence of complement, with rabbit serum containing an antibody that reacts specifically with a distinctive sedimentable constituent of the carcinoma cells. The cellular changes appeared rapidly and were accompanied by an equally rapid loss of viability. The structural changes, as disclosed by histological and cytological methods, including phase contrast microscopy, were described in detail and illustrated. Essentially they were characterized by the entrance of considerable quantities of fluid into the cell, together with swelling and disorganization of its cytoplasm, vesiculation and rupture of the bulk of its cytoplasmic particles, and rapid and virtually complete loss of cytoplasmic basophilism. The plasma membranes, though stretched thin about the swollen cytoplasm of the altered cells, and otherwise changed also, remained unruptured during many hours' observation. The nuclei of the altered cells, however, remained relatively un-changed, their membranes persisting unruptured and their sap remaining wholly transparent and undiminished in amount for long periods, while within it the chromatin retained its staining properties, though sometimes becoming clumped and marginated; by contrast, the nucleoli of the treated cells promptly shrank and lost much of their affinity for the basic dyes. The experimental conditions under which the structural changes became manifest were given in detail, together with an analysis of the findings and brief mention of certain of their implications for cytology and immunology.
Generalized Cutaneous Candidiasis Associated With Diffuse Myopathy and Thymoma
Authors: Leopoldo F. Montes
Journal: JAMA (1968)

Although the coexistence of thymus disease with candidiasis has been mentioned, the association of generalized cutaneous candidiasis with thymoma has apparently been documented only once before. This report describes such an association in a second patient in whom another thymus-related disease, diffuse myopathy, was also present. Surgical removal of the tumor, a thymoma of the spindle cell variety, did not result in improvement of the myopathy nor of the candidiasis. Cutaneous lesions of candidiasis responded to local anticandida agents, but they relapsed when the therapy was discontinued and showed a tendency to worsen when steroid therapy for the myositis was started. It would appear that thymoma should be added to the list of abnormal general states that may predispose to candidiasis.
Abortion, Medicine, and the Law
Authors: Lawrence O. Gostin
Journal: JAMA (1993)

President Clinton now has the opportunity to nominate new associate justices to the US Supreme Court. While the president appropriately states that the nominees' views on abortion will not become a "litmus test," it is clear that the constitutional right to privacy will loom large for both the president and the Senate in choosing associate justices for the court. It is within this charged context of the Supreme Court, society, and reproductive rights that this new edition appears. The new, completely revised<i>Abortion, Medicine, and the Law</i>is an anthology of papers of considerable worth on a subject of abiding interest in American society. The strength of the text is in the internationally recognized scholars on constitutional law (eg, William Van Alstyne and Walter Dellinger), reproductive medicine (eg, EtienneEmile Baulieu and Alan Guttmacher), and ethics (eg, Daniel Callahan and Thomas Murray). When the first three editions of this text were
Excellent <b> <i>In vivo</i> </b> Bystander Activity of Fludarabine Phosphate against Human Glioma Xenografts that Express the <b> <i>Escherichia coli</i> </b> Purine Nucleoside Phosphorylase Gene
Authors: Jeong S. Hong, William R. Waud, Dana N. Levasseur, Tim M. Townes, Hui Wen, Sylvia A. McPherson, Bryan A. Moore, Zsuzsa Bebok, Paula W. Allan, John A. Secrist, William B. Parker, Eric J. Sorscher
Journal: Cancer Research (2004)

Escherichia coli purine nucleoside phosphorylase (PNP) expressed in tumors converts relatively nontoxic prodrugs into membrane-permeant cytotoxic compounds with high bystander activity. In the present study, we examined tumor regressions resulting from treatment with E. coli PNP and fludarabine phosphate (F-araAMP), a clinically approved compound used in the treatment of hematologic malignancies. We tested bystander killing with an adenoviral construct expressing E. coli PNP and then more formally examined thresholds for the bystander effect, using both MuLv and lentiviral vectoring. Because of the importance of understanding the mechanism of bystander action and the limits to this anticancer strategy, we also evaluated in vivo variables related to the expression of E. coli PNP (level of E. coli PNP activity in tumors, ectopic expression in liver, percentage of tumor cells transduced in situ, and accumulation of active metabolites in tumors). Our results indicate that F-araAMP confers excellent in vivo dose-dependent inhibition of bystander tumor cells, including strong responses in subcutaneous human glioma xenografts when 95 to 97.5% of the tumor mass is composed of bystander cells. These findings define levels of E. coli PNP expression necessary for antitumor activity with F-araAMP and demonstrate new potential for a clinically approved compound in solid tumor therapy.
Focus on the target: the tumor microenvironment, Society for Immunotherapy of Cancer Annual Meeting Workshop, October 24th-25th 2012
Authors: Melek Sunay, Francesco Marincola, Samir N Khleif, Samuel C Silverstein, Bernard A Fox, Jerome Galon, Leisha A Emens
Journal: Journal for ImmunoTherapy of Cancer (2013)

The Workshop associated with the 27th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), North Bethesda, MD, October 24-25, 2012 focused on targeting the tumor microenvironment as part of an integrative approach to immune-based cancer therapy.
Lack of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase in fibroblasts from a child with urinary excretion of 3 beta-hydroxy-delta 5-bile acids. A new inborn error of metabolism.
Authors: M S Buchmann, E A Kvittingen, H Nazer, T Gunasekaran, P T Clayton, J Sjövall, I Björkhem
Journal: Journal of Clinical Investigation (1990)

Cultured fibroblasts were shown to be capable of catalyzing the conversion of 7 alpha-hydroxy-cholesterol to 7 alpha-hydroxy-4-cholesten-3-one, an important reaction in bile acid synthesis. The apparent Km was approximately 7 mumol/liter and Vmax varied between 3 and 9 nmol/mg protein per h under the assay conditions used. The assay was used to investigate fibroblasts from a patient who presented with a familial giant cell hepatitis and who was found to excrete the monosulfates of 3 beta, 7 alpha-dihydroxy-5-cholenoic acid and 3 beta, 7 alpha, 12 alpha-trihydroxy-5-cholenoic acid in urine (Clayton, P. T., J. V. Leonard, A. M. Lawson, K. D. R. Setchell, S. Andersson, B. Egestad, and J. Sjövall. 1987. J. Clin. Invest. 79:1031-1038). In addition 7 alpha-hydroxy-cholesterol was found to accumulate in the circulation. Cultured fibroblasts from this boy were completely devoid of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase activity. Fibroblasts from his parents had reduced activity, compatible with a heterozygous genotype. The results provide strong evidence for the suggestion that this patient's liver disease was caused by a primary defect in the 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase involved in bile acid biosynthesis.
Recognition by recombinant autoimmune thyroid disease-derived Fab fragments of a dominant conformational epitope on human thyroid peroxidase.
Authors: S Portolano, G D Chazenbalk, P Seto, J S Hutchison, B Rapoport, S M McLachlan
Journal: Journal of Clinical Investigation (1992)

To characterize the nature of thyroid peroxidase (TPO) autoantibodies present in the sera of patients with autoimmune thyroid disease, we cloned three IgG1/kappa Fab fragments which bind 125I-TPO. This was accomplished by the molecular cloning and expression in bacteria of IgG gene fragments from B cells infiltrating the thyroid of a patient with Graves' disease. The three Fab fragments (SP2, SP4, and SP5) are coded for by a common heavy chain (VH1, D, JH3) and three related, but different, light chains (VK1, JK2). The SP Fab fragments bind specifically to TPO with high affinities (6 x 10(-11)-2 x 10(-10) M) comparable to those of serum TPO autoantibodies. TPO autoantibodies represented by the SP Fab fragments are present in all 11 patients studied, constitute a high proportion (36-72%) of serum TPO autoantibodies in individual patients and interact with a conformational epitope on TPO.
Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration
Authors: Nicole A. Morin, Patrick W. Oakes, Young-Min Hyun, Dooyoung Lee, Y. Eugene Chin, Michael R. King, Timothy A. Springer, Motomu Shimaoka, Jay X. Tang, Jonathan S. Reichner, Minsoo Kim
Journal: The Journal of Experimental Medicine (2008)

Precise spatial and temporal regulation of cell adhesion and de-adhesion is critical for dynamic lymphocyte migration. Although a great deal of information has been learned about integrin lymphocyte function–associated antigen (LFA)-1 adhesion, the mechanism that regulates efficient LFA-1 de-adhesion from intercellular adhesion molecule (ICAM)-1 during T lymphocyte migration is unknown. Here, we show that nonmuscle myosin heavy chain IIA (MyH9) is recruited to LFA-1 at the uropod of migrating T lymphocytes, and inhibition of the association of MyH9 with LFA-1 results in extreme uropod elongation, defective tail detachment, and decreased lymphocyte migration on ICAM-1, without affecting LFA-1 activation by chemokine CXCL-12. This defect was reversed by a small molecule antagonist that inhibits both LFA-1 affinity and avidity regulation, but not by an antagonist that inhibits only affinity regulation. Total internal reflection fluorescence microscopy of the contact zone between migrating T lymphocytes and ICAM-1 substrate revealed that inactive LFA-1 is selectively localized to the posterior of polarized T lymphocytes, whereas active LFA-1 is localized to their anterior. Thus, during T lymphocyte migration, uropodal adhesion depends on LFA-1 avidity, where MyH9 serves as a key mechanical link between LFA-1 and the cytoskeleton that is critical for LFA-1 de-adhesion.
A QUANTITATIVE STUDY OF RECYCLING OF ISOTOPE FROM GLYCINE-1-C14,α-N15 INTO VARIOUS SUBUNITS OF THE URIC ACID MOLECULE IN A NORMAL SUBJECT*
Authors: R. Rodney Howell, Melinda Speas, James B. Wyngaarden
Journal: Journal of Clinical Investigation (1961)

Glycine is the precursor of three atoms of the purine ring, carbons 4 and 5 and nitrogen 7 (1, 2).When glycine-N'5 is administered orally in man N15 is incorporated predominantly into N-7, but N15 is also found in N-1, N-3, and N-9 which are donated not by glycine but by aspartic acid (N-1) and the amide-N of glutamine (N-3 and N-9) (3).The N15 found in N-atoms other than N-7 of uric acid increases with time and may reach 35 per cent of the total N15 after several days (1).In contrast, when glycine-1-C14 is administered orally in man the isotope labels C-4 of uric acid almost exclusively, and very little C14 is incorporated into other carbon atoms by secondary pathways (4).As a consequence of these diverse fates of the a-N15 and 1-C4 atoms of glycine, the N15/C14 ra- tio in uric acid exceeds 1.0 after administration of doubly labeled glycine (5).Values of 1.7 and 1.8 were reported in control subjects, and of 2.0 to 2.8 in gouty subjects by Gutman and co-workers (5).Their results further suggested that the ratio of (N15 in N-7)/(Cl4 in uric acid) was also greater than 1.0.In one "normal excretor" gouty subject the ratios were generally in excess of 1.2.Additionally, ratios of 1.08 to 1.92 (mean, 1.34) and of 0.86 to 1.37 (mean, 1.16) were calculated for two nongouty control subjects, the same (N15 in N-7) /(total N15 in uric acid) assumed as in one normal subject studied by Shemin and Rittenberg (1).An incorporation of glycine-N'5 into N-7 greater than of glycine-1-C"4 into C-4 would have important implications that might signify either an accessory pathway of purine synthesis, or a dis- parity in the rates of "isotopic turnover" of the a-N and 1-C of glycine.There are known mecha-
Entries and operations: The great divide and the pitfalls of form frequency
Authors: Joan Sereno, Pienie Zwitserlood, Allard Jongman
Journal: Behavioral and Brain Sciences (1999)

Results from our laboratories show clear frequency effects for regularly inflected forms in both German and English. Moreover, there does not seem to be sufficient evidence to treat the -s plural as the default plural in German. Together, these data do not support a dual modular structure of the language faculty.
Gene Expression Profiling in Cervical Cancer: An Exploration of Intratumor Heterogeneity
Authors: Barbara Bachtiary, Paul C. Boutros, Melania Pintilie, Willa Shi, Carlo Bastianutto, Jian-Hua Li, Joerg Schwock, Wendy Zhang, Linda Z. Penn, Igor Jurisica, Anthony Fyles, Fei-Fei Liu
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To explore intratumor heterogeneity in gene expression profiles from patients with cervical cancer. Experimental Design: A total of 33 biopsies were obtained from 11 patients, sampling between two and five different areas for each tumor. The extracted RNA was hybridized onto the Affymetrix U133 Plus 2.0 oligonucleotide chip. The variance of expression within a patient (W), between patients (B) and the total variance (T = W + B) were calculated for each ProbeSet, and the ratio W/T was used as a measure of intratumor heterogeneity. Gene Ontology functional analysis was done to assess the function of genes that had high W/T (top 10%) and low W/T (bottom 10%) values. Results: In total, 448 ProbeSets (2.2% of the total) had W/T &amp;lt; 0.10, indicating low intratumor heterogeneity, and 537 ProbeSets (2.7% of the total) had W/T &amp;gt; 0.90, indicating high intratumor heterogeneity. In total 14,473 ProbeSets (72.4%) had higher intertumor than intratumor heterogeneity (W/T &amp;lt; 0.5). Genes with low intratumor heterogeneity were characterized by a statistically significant enrichment of immune-related functions (P &amp;lt; 0.0001). Genes with high intratumor heterogeneity were characterized by a significant tendency towards nuclear localization and nucleic acid binding (both P &amp;lt; 0.0001). For genes with W/T &amp;gt; 0.5, more than six biopsies would be required to minimize the intratumoral heterogeneity to &amp;lt;0.15; if W/T is 0.3 to 0.4, four biopsies are required; and for low W/T of 0.16 to 0.3, only two to three biopsies would be needed. Conclusion: Although the intratumor heterogeneity was low for the majority of the tested ProbeSets, for many genes, multiple biopsies are required to obtain a reliable estimate of gene expression.
Nifedipine Indirectly Upregulates Superoxide Dismutase Expression in Endothelial Cells via Vascular Smooth Muscle Cell–Dependent Pathways
Authors: Keisuke Fukuo, Jin Yang, Osamu Yasuda, Masaki Mogi, Toshimitsu Suhara, Naoyuki Sato, Takashi Suzuki, Shigeto Morimoto, Toshio Ogihara
Journal: Circulation (2002)

Calcium antagonists normalize endothelial dysfunction in many cardiovascular diseases. There is no known receptor, however, for calcium antagonists in endothelial cells (ECs). We hypothesized that vascular smooth muscle cells (VSMCs) are involved in the mechanism underlying the normalization of endothelial dysfunction by calcium antagonists.Coculture studies with ECs and VSMCs were performed to determine whether VSMCs mediate modulation of endothelial superoxide dismutase (SOD) activity and expression induced by the calcium antagonist nifedipine. Nifedipine induced upregulation of SOD activity in rat aortic segments but had no effect on SOD expression or activity in ECs or VSMCs cultured individually. When ECs were cocultured with VSMCs, however, nifedipine upregulated SOD expression and activity in ECs. Nifedipine stimulated vascular endothelial growth factor (VEGF) production from VSMCs, and this stimulation of VEGF production was abolished by HOE-140, an antagonist of the bradykinin B(2) receptor. A neutralizing antibody against VEGF inhibited the upregulation of endothelial SOD by nifedipine. In addition, recombinant VEGF induced an increase in the levels of SOD expression in ECs, and supernatant derived from nifedipine-treated VSMCs enhanced NO production from ECs. This increase in NO production by the supernatant was inhibited by preincubation of ECs with SOD antisense oligodeoxyribonucleotides.The calcium antagonist nifedipine indirectly upregulates endothelial SOD expression by stimulating VEGF production from adjacent VSMCs. This finding may provide further insight into the mechanism underlying the beneficial effects of calcium antagonists in cardiovascular diseases.
Control of proliferation in astrocytoma cells by the receptor tyrosine kinase/PI3K/AKT signaling axis and the use of PI-103 and TCN as potential anti-astrocytoma therapies
Authors: D. B. Gursel, Y. S. Connell-Albert, R. G. Tuskan, T. Anastassiadis, J. C. Walrath, J. J. Hawes, J. C. Amlin-Van Schaick, K. M. Reilly
Journal: Neuro-Oncology (2011)

A growing body of work suggests that astrocytomas and glioblastoma multiforme will require carefully tailored, molecularly targeted therapy for successful treatment. Recent efforts to comprehensively identify mutations and gene expression changes in glioblastoma have shown that mutation of NF1 is a common alteration in human glioblastoma. We have developed and characterized a panel of 14 tumor lines from grades II through IV astrocytomas developed from our Nf1−/+;Trp53−/+cis mouse model and have used this panel to characterize signal transduction pathways and inhibitors that are candidate therapeutic targets for astrocytoma and glioblastoma. We show that these tumors express platelet-derived growth factor receptor–α, epidermal growth factor receptor, and their respective ligands to varying degrees. We find that both the MEK and PI3K signaling pathways downstream of epidermal growth factor receptor and platelet-derived growth factor receptor–α are necessary for full proliferation of astrocytoma cells; however, inhibition of the PI3K pathway is more effective than inhibition of MEK at blocking cell growth. We have examined inhibitors of the PI3K/Akt/mTOR signaling pathway and find that PI-103 and TCN show particular promise for inhibiting growth in Nf1 and Trp53 mutant astrocytoma cells.
Telomerase-Specific Replication-Selective Virotherapy for Human Cancer
Authors: Takeshi Kawashima, Shunsuke Kagawa, Naoya Kobayashi, Yoshiko Shirakiya, Tatsuo Umeoka, Fuminori Teraishi, Masaki Taki, Satoru Kyo, Noriaki Tanaka, Toshiyoshi Fujiwara
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Replication-selective tumor-specific viruses present a novel approach for treating neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis, and its activity is closely correlated with human telomerase reverse transcriptase (hTERT) expression. We investigated the antitumor effect of the hTERT-specific replication-competent adenovirus on human cancer cells. Experimental Design: We constructed an adenovirus 5 vector [tumor- or telomerase-specific replication-competent adenovirus (TRAD)], in which the hTERT promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site, and we examined the selective replication and antitumor effect in human cancer cells in vitro and in vivo. Results: TRAD induced selective E1A and E1B expression in human cancer cells, but not in normal cells such as human fibroblasts. TRAD replicated efficiently and induced marked cell killing in a panel of human cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal human fibroblasts lacking telomerase activity. In nu/nu mice carrying s.c. human lung tumor xenografts, intratumoral injection of TRAD resulted in a significant inhibition of tumor growth. No evidence of TRAD was identified in tissues outside of the tumors, despite the presence of TRAD in the circulation. Moreover, TRAD replication in the distant, noninjected tumors was demonstrated. Conclusions: Our results suggest that the hTERT promoter confers competence for selective replication of TRAD in human cancer cells, an outcome that has important implications for the treatment of human cancers.
Impact of treatment of sleep apnoea on left ventricular function in congestive heart failure
Authors: M T Naughton
Journal: Thorax (1998)

4Whether ‚ adrenergic blockers oVer a true survival benefit is currently debated. 56 Clearly, other therapeutic modalities need to be developed. This brief review discusses the role of sleep apnoea and its reversal with continuous positive airway pressure (CPAP) in patients with CHF. Discussion will focus initially upon the rationale for CPAP in acute unstable and chronic stable CHF. Thereafter, the influence of long term treatments of sleep apnoea (CPAP and other treatments) on cardiac function in patients with chronic CHF will be discussed. As early as 1936 positive airway pressure was used to treat acute cardiogenic pulmonary oedema. 7 Since then, many clinicians have reported improvements in cardiopulmonary physiology such as arterial blood gas tensions and work of breathing in patients with acute cardiogenic pulmonary oedema who were mechanically ventilated with positive end expiratory pressure (PEEP). 8 Similar reports were observed in patients with cardiogenic pulmonary oedema breathing spontaneously with CPAP
How does mechanical insufflation:exsufflation (MI:E) affect lung recruitment? A patient case study
Authors: Ema Swingwood, Emma Forster
Journal: European Respiratory Journal (2014)

Background: MI:E is a non invasive device that alternates positive (insufflation) and negative (exsufflation) pressures to facilitate secretion clearance. Research demonstrates the ability of MI:E to enhance peak cough flow and peak expiratory flow rates in adult and paediatric populations. No studies have explored how MI:E and its use of alternating positive and negative pressures effects lung recruitment.  Aims: This observational case study aims to examine the effects of MI:E on lung recruitment.  Methods: The patient completed a 2 minute period of quiet breathing, followed by a MI:E treatment session and a further 2 minutes of quiet breathing. Regional lung ventilation (RLV) via electrical impedance tomography (EIT) (Pulmovista 500, Drager) and oxygen saturations were measured throughout.  Results: RLV increased from baseline during insufflations. The exsufflation breath caused a dramatic reduction in RLV Multiple reinsufflation breaths were required to regain baseline RLV. Oxygen saturations remained unchanged throughout the monitoring period  .  Conclusions: Insufflation breaths have the ability to recruit lung units. The exsufflation breath caused de-recruitment which may leave a patient vunerable to clinical deterioration. Results gained were from a single patient case study; application into a wider clinical setting should therefore occur with caution. Further investigation using a larger population is required.