tbuckley/cabot-search huggingface dataset:
Abstract 106: A requirement for FADD and its phosphorylation for KRAS-driven oncogenesis
Authors: Brittany M. Bowman, Stefanie Galban, Benjamin A. Hoff, Kevin A. Heist, Jennifer L. Boes, Craig J. Galban, Rajiv M. Patel, Jianke Zhang, Brian D. Ross, Alnawaz Rehemtulla
Journal: Cancer Research (2014)

Abstract Lung cancer accounts for 27% of all cancer deaths worldwide. 80% of these deaths are due to a specific subtype Non-small cell lung cancer (NSCLC). Almost half of all NSCLC patients carry gatekeeper mutations in the EGFR/KRAS pathway. Although KRAS mutations are the most prevalent mutations in human cancers, therapies targeting KRAS have fallen short. Tyrosine kinase inhibitors have been successful in NSCLC patients with mutant or amplified EGFR, however resistance to these inhibitors is common. Thus therapies targeting mutant KRAS or its downstream effectors are desperately needed for the treatment of NSCLC. FAS Associated Death Domain (FADD) is a well characterized adaptor protein involved in death receptor mediated apoptosis, but more recently has been implicated in the regulation of other cellular functions such as cell cycle and proliferation. Increasing evidence suggests that it is FADD's phosphorylated state which regulates these non-apoptotic signaling pathways. We and others have previously identified phosphorylated FADD as a predictor of aggressiveness and clinical stage in lung and head and neck cancer patients, respectively. Using non-invasive bioluminescence and µCT imaging in a Kras driven mouse model of NSCLC, we demonstrate the requirement for FADD in tumor progression. Lung-specific activation of KrasG12D and simultaneous FADD deletion resulted in reduced lung tumor burden. Furthermore lung lesions of KrasG12D FADD null mice were significantly smaller with a decrease in proliferative index. Similar findings were obtained in MEFs, where siRNA mediated Kras knockdown or the use of MEK inhibitors resulted in a Kras dependent decrease in FADD phosphorylation, decrease in cell cycle progression and cell proliferation. These data propound the phosphorylation of FADD as a downstream event of Kras signaling and demonstrate its requirement for Kras dependent neoplasia in a mouse model for NSCLC. In summary our findings demonstrate that elevated FADD and phosphorylated FADD levels are predictive of poor survival in an animal model of NSCLC agreeing with clinical findings. Furthermore, it implicates phosphorylation of FADD downstream of KRAS activation and thus suggests FADD phosphorylation as a valid target in the treatment of NSCLC patients. Citation Format: Brittany M. Bowman, Stefanie Galban, Benjamin A. Hoff, Kevin A. Heist, Jennifer L. Boes, Craig J. Galban, Rajiv M. Patel, Jianke Zhang, Brian D. Ross, Alnawaz Rehemtulla. A requirement for FADD and its phosphorylation for KRAS-driven oncogenesis. [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 106. doi:10.1158/1538-7445.AM2014-106
Controversy on reperfusion arrhythmias
Authors: D. D. BONO, C. J GARRATT
Journal: Cardiovascular Research (1993)

Controversy on reperfusion arrhythmias Get access DAVID DE BONO, DAVID DE BONO Division of Cardiology, Faculty of Medicine, University of Leicester, Leicester. UK Search for other works by this author on: Oxford Academic PubMed Google Scholar CLIFFORD J GARRATT CLIFFORD J GARRATT Division of Cardiology, Faculty of Medicine, University of Leicester, Leicester. UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 11, November 1993, Pages 2081–2082, https://doi.org/10.1093/cvr/27.11.2081 Published: 01 November 1993
Prognostic significance of DNA-binding capacity patterns in patients with lupus nephritis.
Authors: M K Adler, A Baumgarten, B Hecht, N J Siegel
Journal: Annals of the Rheumatic Diseases (1975)

The time course of DNA binding capacity (DNA-bc) was found to correlate with the clinical course in a group of 21 patients who had biopsy-proven lupus glomerulonephritis and were treated with immunosuppressive agents. Eight patients showed a sequential DNA-bc pattern in which a high titre of anti-DNA antibody was present for a prolonged period of time all having an unfavourable clinical course. Persistently high values of DNA-bc preceded by as much as 10 months evidence of renal deterioration obtained by conventional renal function tests. Thirteen patients showed a low titre of anti-DNA antibody throughout most of their course, 12 having a favourable outcome. An initially high value of DNA-bc had no prognostic significance. These results suggest that the persistence of a high titre of anti-DNA antibody in patients with lupus glomerulonephritis is a poor prognostic sign.
A case of primary cutaneous anaplastic large cell lymphoma with variant anaplastic lymphoma kinase translocation
Authors: K. Sasaki, M. Sugaya, H. Fujita, K. Takeuchi, H. Torii, A. Asahina, K. Tamaki
Journal: British Journal of Dermatology (2004)

Anaplastic lymphoma kinase (ALK) is frequently observed in systemic anaplastic large cell lymphoma (ALCL), mostly in childhood or adolescence, but only rarely in primary cutaneous cases. We report a case of primary cutaneous ALCL (pcALCL) with cytoplasmic ALK expression. A 54‐year‐old woman with an ulcerative tumour on her forehead was admitted to our hospital. Histologically, there was an infiltrate consisting of atypical large lymphocytes and small lymphocytes in the dermis and fat tissue. Southern blot analysis showed monoclonal T‐cell receptor Cβ1 gene rearrangement. Atypical large lymphocytes were positive for CD30, CD4 and CD25, and negative for CD3 and CD79a. They were also positive for ALK only in the cytoplasm, and neurophosmin (NPM)‐ALK fusion transcript was not detected by reverse transcription‐polymerase chain reaction. This suggested that the translocation partner of the ALK gene in this case was different from NPM (variant translocation). The tumour on the forehead resolved in 1 month after biopsy. Nodular lesions recurred on the right knee, and were histologically identical with the forehead lesion. Our case suggests the existence of a subgroup with variant ALK translocation in pcALCL; examining NPM‐ALK translocation in each case with ALK expression should be useful to characterize the disease further.
Prolongation of Overall Survival in Advanced Lung Adenocarcinoma Patients with the XAGE1 (GAGED2a) Antibody
Authors: Yoshihiro Ohue, Koji Kurose, Yu Mizote, Hirofumi Matsumoto, Yumi Nishio, Midori Isobe, Minoru Fukuda, Akiko Uenaka, Mikio Oka, Eiichi Nakayama
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The cancer/testis antigen XAGE1 (GAGED2a) is expressed in approximately 40% of advanced lung adenocarcinomas. We investigated the clinical relevance of the XAGE1 (GAGED2a) immune responses in patients with advanced lung adenocarcinoma. Experimental Design: The XAGE1 (GAGED2a) antigen expression and EGFR mutation were determined with tumor tissues. The XAGE1 (GAGED2a) antibody and T-cell immune responses, as well as immune cell phenotypes, were analyzed with blood samples. Patients with EGFR wild-type (EGFRwt) tumors were treated with conventional platinum-based doublet chemotherapy and patients with EGFR-mutated (EGFRmt) tumors were treated with EGFR-TKI and conventional chemotherapy. The overall survival (OS) rates of the antibody-positive and -negative patients were investigated. Results: The results showed that the OS of antibody-positive patients was prolonged significantly compared with that of antibody-negative patients with either XAGE1 (GAGED2a) antigen-positive EGFRwt (31.5 vs. 15.6 months, P = 0.05) or EGFRmt (34.7 vs. 11.1 months, P = 0.001) tumors. Multivariate analysis showed that the presence of the XAGE1 (GAGED2a) antibody was a strong predictor for prolonged OS in patients with XAGE1 (GAGED2a) antigen-positive tumors and in patients with either EGFRwt or EGFRmt tumors. On the other hand, XAGE1 (GAGED2a) antigen expression was a worse predictor in patients with EGFRmt tumors. Phenotypic and functional analyses of T cells indicated immune activation in the antibody-positive patients. Conclusions: The findings suggest that production of the XAGE1 (GAGED2a) antibody predicts good prognosis for patients with lung adenocarcinoma as an immune biomarker and the protective effect of this naturally occurring immune response supports the concept of immunotherapy. Clin Cancer Res; 20(19); 5052–63. ©2014 AACR.
Weight Control Practices and Disordered Eating Behaviors Among Adolescent Females and Males With Type 1 Diabetes
Authors: Dianne Neumark-Sztainer, Joan Patterson, Alison Mellin, Diann M. Ackard, Jennifer Utter, Mary Story, Joseph Sockalosky
Journal: Diabetes Care (2002)

This study examines the prevalence of specific weight control practices/disordered eating behaviors and associations with sociodemographic characteristics, BMI and weight perceptions, family functioning, and metabolic control among adolescent females and males with type 1 diabetes.The study population included 70 adolescent females and 73 adolescent males with type 1 diabetes who completed the AHEAD (Assessing Health and Eating among Adolescents with Diabetes) survey. Data on BMI and glycosylated hemoglobin (HbA(1c)) were drawn from medical records.Unhealthy weight control practices were reported by 37.9% of the females and by 15.9% of the males. Among the females, 10.3% reported skipping insulin and 7.4% reported taking less insulin to control their weight. Only one male reported doing either of these behaviors. Weight control/disordered eating behaviors were not associated with age, parental level of education, family structure, or race/ethnicity. Higher levels of weight dissatisfaction tended to be associated with unhealthy weight control/disordered eating; associations with BMI were inconsistent. Family cohesion was negatively associated with disordered eating among females (r = -0.52; P < 0.001) and males (r = -0.41; P < 0.001), but correlations with other measures of family environment (control, independence, and responsibility for diabetes management) were not significant. Correlations between disordered eating and HbA(1c) levels were significant among females (r = 0.33; P < 0.01) and males (r = 0.26; P < 0.05).Special attention is needed for youth with weight concerns and those from less cohesive families to assist in the development of healthy diabetes management behaviors.
Tinea capitis in south-east London: an outbreak of <i>Trichophyton tonsuraus</i> infection
Authors: L.C. Fuller, F.C. Child, E.M. Higgins
Journal: British Journal of Dermatology (1997)

Journal Article Tinea capitis in south‐east London: an outbreak of Trichophyton tonsuraus infection Get access L.C. Fuller, L.C. Fuller King's College Hospital Medical School, London U.K. Search for other works by this author on: Oxford Academic Google Scholar F.C. Child, F.C. Child King's College Hospital Medical School, London U.K. Search for other works by this author on: Oxford Academic Google Scholar E.M. Higgins E.M. Higgins King's College Hospital Medical School, London U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 136, Issue 1, 1 January 1997, Page 139, https://doi.org/10.1111/j.1365-2133.1997.tb08771.x Published: 01 January 1997
Abstract 3507: Type 17-1-CD8+ T cells (Tc17-1) as potent effector cells for immunotherapy of brain tumors
Authors: Takayuki Ohkuri, Akemi Kosaka, Maki Ikeura, Adam Litterman, John Ohlfest, Hideho Okada
Journal: Cancer Research (2012)

Abstract Malignant gliomas, such as glioblastoma multiforme (GBM), are the most common and dismal primary brain tumors, and there is a strong need for developing novel and effective therapeutic modalities. Although the central nervous system (CNS) and CNS tumors are often considered immunologically privileged, as demonstrated by studies on CNS autoimmunity, activated autoreactive T-cells, especially T helper (Th) 17 cells, infiltrate through the blood brain barrier (BBB) and mediate antigen-specific responses in the CNS. Especially, Th17 express high levels of CCR6, which has a crucial role in Th17 infiltration into the CNS. In addition to Th17 cells, a new putative subtype of IL-17-producing CD4+ T cells with CD4+IL-17+IFN-γ+ (Th17-1 cells) double-positive phenotype has also been identified. Based on our previous studies demonstrating a critical role of Th1-chemokine CXCL10 and its receptor CXCR3 for effective T-cell trafficking in CNS tumors, we hypothesized that Th17-1 cells and CD8+ T cells producing IL-17 and IFN-γ (hereby Type-17-1 CD8+ T-cells) will demonstrate superior CNS tumor infiltration compared with Th1 cells due to the activation of two CNS-relevant chemokine pathways, CXCL10-CXCR3 and CCL20-CCR6. Mouse Tc17, Tc17-1 and Tc1 cells generated from Pmel-1 mouse-derived naïve CD8+ T cells expressed high CCR6 and low CXCR3, high CCR6 and high CXCR3, and little CCR6 and high CXCR3, respectively. Although Tc17 displayed lower levels of antigen-specific cytotoxic activity compared with Tc17-1 and Tc1 in a 4 hr cytotoxic assay, Tc17 killed tumor cells more effectively than the other populations in long-term cultures (4 to 6 days). While Tc1 cells underwent apoptosis due to their exhausted state, Tc17-1 maintained strong cytotoxicity and proliferative activities even after 4 day co-culture with tumor cells. Moreover, the supernatant derived from activated Tc17 and Tc17-1 induced CCL20 and CXCL10 in the GL261 glioma cells while Tc1-derived supernatant induced CXCL10 but not CCL20. These results suggest a possibility that Tc17-1 may elicit persistent anti-CNS tumor responses and induce both CCL20 and CXCL10 in the CNS tumor microenvironment, thereby attracting additional effector cells to the site. In vivo studies in mice bearing CNS gliomas are warranted to determine whether adoptively transferred Tc17-1 infiltrate to the CNS tumor site and mediate superior anti-tumor response compared with Tc1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3507. doi:1538-7445.AM2012-3507
THE SITE OF OPERATION FOR EMPYEMA
Authors: D. C. L. Fitzwilliams
Journal: BMJ (1921)

J l_ 1UhE I .-mm"3O*biw el B. sporogenes and B. bifermentans subcutaneously, Vroduced no visible effect on the development of rickets in rats.4. The deficiency of the diet in calcium alone can produce changes in the skeleton of rats which present some resemblances with rickets, especially when the young rats have originated from a mother kept on the same diet during lactation. Usually deficiency of food in vitamin A producesSu rats impoverishment of the bones in calcium, enrich- ment in water, and osteoporosis with deficient osteogenesis, and in some cases a picture resembling slight rickets.Changes in the skeleton more similar to rickets, and in some cases typical of rickets, were observed in young rats on -A diet, provided their parents had been fed on -A diet during conception, pregnancy, and lactation.6. Vitamin A has a relation to the metabolism of calcium In the organism and particularly in the bones, and therefore to the development of rickets.7. My few experiments on the feeding of parents on food deficient in vitamin A or calcium during conception, pregnancy, and lactation suggest that this may start disturbances of metabolism in the child which, if the deficient dietary be continued after birth, result in serious disorders of the skeleton.
Human allograft acceptance is associated with immune regulation
Authors: A.M. VanBuskirk, W.J. Burlingham, E. Jankowska-Gan, T. Chin, S. Kusaka, F. Geissler, R.P. Pelletier, C.G. Orosz
Journal: Journal of Clinical Investigation (2000)

The ultimate goal of transplantation is drug-free allograft acceptance, which is rarely encountered in transplant recipients. Using a novel human-to-mouse "trans vivo" delayed-type hypersensitivity assay, we assessed donor-reactive cell-mediated immune responses in kidney and liver transplant patients, four of whom discontinued all immunosuppression. One of these subjects (J.B.) rejected his graft after 7 years of stable function, while the others (D.S., R.D., M.L.) continue to have excellent graft function 5, 28, and 4 years after the cessation of immunosuppression. PBMCs from J.B. exhibited strong responses to both donor and recall antigens whereas PBMCs from patients D.S., R.D., and M.L. responded strongly to recall, but not donor, antigens. Furthermore, when donor and recall antigens were colocalized, the recall response in these three patients was inhibited. This donor antigen–linked nonresponsiveness was observed in four other patients who are still maintained on immunosuppression. The weakness of donor-reactive DTH responses in these patients is due to donor alloantigen-triggered regulation that relies on either TGF-β or IL-10. In D.S., regulation is triggered by a single donor HLA Class I antigen, either in membrane-bound or soluble form. This demonstrates that allograft acceptance in humans is associated with an immune regulation pattern, which may be useful in the diagnosis and/or monitoring of transplant patients for allograft acceptance.
Observations on the Anatomy of the Intrasegmental Bronchial Tree
Authors: J. Hayward, L. McA. Reid
Journal: Thorax (1952)

Miller's (1947) detailed description of the pulmonary lobule remains a classic, and the work of Nelson (1932Nelson ( , 1934)), Foster-Carter (1942), andBrock (1946) on the larger bronchi and their distribution has firmly established the bronchopulmonary segment as a concept which forms a basis for localization of lung disease.But the bronchial tree between the segmental bronchi and the respiratory bronchioles has received less attention than its due.No clear description of its arrangement has been made.An investigation, begun with the intention of studying the morbid anatomy of bronchiectasis, soon revealed the urgent need for further examination of this neglected region of the bronchial tree, because it is here that the dilatation of bronchiectasis occurs.The investigations described below were therefore carried out, and an attempt will be made in this paper to describe the intrasegmental bronchial tree and, on this basis, to give a method of localizing disease processes in this zone. METHODS OF EXAMINATIONObservations were made on normal and pathological specimens and on broncho- grams.In addition to 20 normal examples of each, operation specimens and bronchograms from 40 patients with cylindrical bronchiectasis were used.This was possible because in a study of bronchiectasis (Reid, 1950) it was shown that in this type of the disease the normal pattern of bronchial arborization is preserved.In these cases the bronchioles in the diseased segments fail to fill with oil.This makes their bronchograms particularly useful for observing the mode of branching of the bronchi, which are not obscured, as is so often the case in normal bronchograms, by the shadows of oil in overlying bronchioles and alveoli.Immediately after removal from the body both operation and post-mortem specimens were fixed by inflation with 8% formol-saline through the bronchial tree, and before being cut they were left in the solution for seven to 10 days.The bronchi were exposed by cutting along their length with scissors.The side branches thus exposed could then in their turn be followed.It was sometimes necessary to pare away lung tissue to expose the branches more satisfactorily.
SCHIZOPHRENIC SYMPTOMATOLOGY IN MENTALLY RETARDED CHILDREN
Authors: JOSEPH WORTIS
Journal: American Journal of Psychiatry (1958)

In summary, I think we should make a break with the facile generalizations that seem to simplify but really complicate and distort our work. There is no single entity of mental retardation: there are a great variety of factors, medical, psychological and social, which may impede mental growth and development. Similarly, there is no simple entity of schizophrenia: here too we encounter a variety of medical, social and psychological factors which induce bizarre distortions and disorganized patterns of behavior and development. Where the intellectual retardation dominates the picture, we are justified in labeling it descriptively as mental retardation: where the distortion and disorganization dominate the picture, we are justified in calling its schizophrenia. But we must recognize that there are many intermediate and overlapping types where we must be satisfied to describe the picture as retardation, with more or less prominent schizophrenic features. Moreover, in point of time, the clinical picture may change in any one case and latent or secondary features may become dominant. There is much to recommend Benda's(3) suggestion that cerebral defect or dysfunction present at birth is more likely to produce a picture of retarded development, while the same process superimposed later, after a period of normal development, is more likely to induce a pattern of disorganization that is called psychotic. This may be compared to the building of a small structure with a few bricks, or the later undermining or demolition of a good-sized building by removing bricks after the building is completed. In terms of research and scientific interest, it is reasonable to expect that some common etiologic factors may induce both syndromes; it can be regarded as already established that certain kinds of cerebral pathology or dysfunction can induce both retardation and schizophrenia. Post-anoxic, post-encephalitic, and phenylketonuric cerebral dysfunction can all demonstrably induce psychoses, mental retardation, or combinations of both. It is proper to suspect that other etiologic agents can do the same. At the same time, it would not be at all surprising to find that the hard core of schizophrenic cases, and the hard core of retarded cases, tend to have different types of etiology, with ganglion cell destruction and cerebral defect dominant in retardation, and toxic inhibitory factors dominant in schizophrenia. This was Kraepelin's view when he first propounded the concept of dementia praecox and there is much new work to indicate that his view may prove to be correct.
Anticoagulant drugs in the elderly.
Authors: T. F. Fannin, W. J. Gray
Journal: BMJ (1989)

the relative risk of vertical transmission of herpes simplex virus.Medicolegally it would be difficult to defend a case of neonatal herpes in which antenatal maternal virological screening had not been performed on a woman with a history of genital herpes.Although systemic administration of acyclovir does not produce teratogenic effects in animal studies, experience in humans is limited.Oral acyclovir is offered to women with primary genital herpes during pregnancy with a warning of the possibility of unknown risks.The use of acyclovir in late pregnancy for women with an episode of recurrent herpes virus infection remains contro- versial.