tbuckley/cabot-search huggingface dataset:
Ligand-dependent EphB1 signaling suppresses glioma invasion and correlates with patient survival
Authors: L. Teng, M. Nakada, N. Furuyama, H. Sabit, T. Furuta, Y. Hayashi, T. Takino, Y. Dong, H. Sato, Y. Sai, K.-i. Miyamoto, M. E. Berens, S.-G. Zhao, J.-I. Hamada
Journal: Neuro-Oncology (2013)

Extensive evidence implicates the Eph receptor family of tyrosine kinases and its ligand, ephrin, in glioma invasion, but it remains incompletely understood how these receptors affect chemotactic behavior of glioma. We sought to identify the Eph family members that correlate with patients' survival and to reveal the function of Eph in glioma invasion. Clinical relevance of EphB genes was confirmed in a clinically annotated expression data set of 195 brain biopsy specimens. The function of EphB was analyzed in vitro and in vivo. Levels of mRNA of certain EphB members were significantly different in histological grades of glioma. According to Kaplan–Meier analysis, only the EphB1 level among 5 members of EphB emerged to be a powerful predictor of favorable survival in malignant glioma (n = 97, P = .0048), although the levels of EphB1 expression did not vary across the tumor grades. Immunoprecipitation showed that tyrosine phosphorylated EphB1 was not detected in all glioma cells tested. Forced overexpression and autophosphorylation of EphB1 in low expressor cell lines (U251, U87) did not affect cell migration or invasion in vitro, whereas EphB1 phosphorylation induced by ephrin-B2/Fc significantly decreased migration and invasion. Cells expressing ephrin-B2 showed noteworthy morphological changes consistent with migration induction; this alteration was negated by EphB1 overexpression. Concomitantly, overexpression of EphB1 abrogated the increased migration and invasion induced by ephrin-B2 in vitro and in vivo. These data suggest that ligand-dependent EphB1 signaling negatively regulates glioma cell invasion, identifying EphB1 as a favorable prognostic factor in malignant glioma.
Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity
Authors: Takashi Kakinuma, Koichiro Nakamura, Motoshi Wakugawa, Hiroshi Mitsui, Yayoi Tada, Hidehisa Saeki, Hideshi Torii, Akihiko Asahina, Nobuyuki Onai, Kouji Matsushima, Kunihiko Tamaki
Journal: Journal of Allergy and Clinical Immunology (2001)
Correlates of <i>SYT-SSX</i> Fusion Type in Synovial Sarcoma: Getting More Complex But Also More Interesting?
Authors: Marc Ladanyi
Journal: Journal of Clinical Oncology (2005)

approximately to the year 1995, when Finland had in only 5 years completed a targeted mammography screening of women aged 50 to 59 years with 90% coverage. 2,3oincidentally, the incidence of breast cancer doubled in the screened age groups.In Germany, some 2% of the female population aged 50 years or older were thought to undergo mammography, 2 and the age-incidence pattern for Germany in Figure 1 resembles that of Finland from the premammography period.Second, a summary of four randomized trials reported an overall relative risk of 1.27 for breast cancer among HRT users. 4Considering that in Finland only 20% of women aged 45 to 64 years were HRT users, 5 the risk would need to be very high among the HRT users (about six-fold) to explain the doubling of the risk for breast cancer, counter to the results of the randomized trials.We are in the process of assessing age-specific incidence changes for breast cancer in various countries by correlating them to the offered mammography programs, and the data appear consistent with the Swedish experience in support of the main contribution of mammography. 6,7Another question that we hope to resolve is the possible bias of the screening and diagnostic techniques on familial risk of breast cancer, which would have implications to familial risk estimation and recommendations to mutation testing.
HEMOGLOBIN PRECIPITATION IN RENAL TUBULES
Authors: Charles L. Yuile, Michael A. Gold, Ewart G. Hinds
Journal: The Journal of Experimental Medicine (1945)

1. A readily reproducible pathological lesion closely resembling that typical of the "transfusion kidney" has been obtained by the injection of hemoglobin into rabbits having acid urine, whose renal tubules had previously been damaged to a moderate degree by (a) a short period of complete renal ischemia, or (b) the administration of a specific chemical poison-sodium tartrate. 2. It has been found that hemoglobin is precipitated in the tubules of damaged kidneys excreting either acid or alkaline urine, in contrast to the absence of hemoglobin precipitation in normal kidneys. 3. In the acid state hemoglobin casts are more numerous and more persistent than in the alkaline, and are associated with renal functional disturbances, in contrast to the lack of such disturbances when the urine is alkaline. 4. The ultimate outcome, both anatomically and functionally, in any given instance is determined by variations in the degree of tubular damage, the level of hemoglobinemia, and the urinary pH.
Familial hypercholesterolemia, tendinous xanthomas, and Frans Hals
Authors: D. W. Erkelens
Journal: JAMA (1989)

To the Editor.—  Although the molecular mechanisms underlying familial hypercholesterolemia have only recently been described,1Frans Hals, the 17th-century Dutch painter, was probably the first to observe the tendinous xanthomas that accompany the clinical disorder. In the December 9, 1988, issue ofJAMA, the painting on the cover,Portrait of an Elderly Lady, shows the classic tendinous lesions on the dorsum of the hands of a 60-year-old woman who probably had heterozygous familial hypercholesterolemia.2There is no evidence in the painting that she had xanthelasma as well. Although the clinical diagnosis was not made by Dr Southgate, and the woman's fingers were described as gnarled and swollen, the cause of the lesions seems clear.  Hypercholesterolemia is a common abnormality in the Netherlands, although it is mostly on a polygenic and/or dietary basis. Heterozygous familial hypercholesterolemia occurs in only 1 per 500 people, while the homozygous form is much more
Adaptive Evolution of Sperm Bindin Tracks Egg Incompatibility in Neotropical Sea Urchins of the Genus Echinometra
Authors: Michael A. McCartney, H. A. Lessios
Journal: Molecular Biology and Evolution (2004)

Bindin is a gamete recognition protein known to control species-specific sperm-egg adhesion and membrane fusion in sea urchins. Previous analyses have shown that diversifying selection on bindin amino acid sequence is found when gametically incompatible species are compared, but not when species are compatible. The present study analyzes bindin polymorphism and divergence in the three closely related species of Echinometra in Central America: E. lucunter and E. viridis from the Caribbean, and E. vanbrunti from the eastern Pacific. The eggs of E. lucunter have evolved a strong block to fertilization by sperm of its neotropical congeners, whereas those of the other two species have not. As in the Indo-West Pacific (IWP) Echinometra, the neotropical species show high intraspecific bindin polymorphism in the same gene regions as in the IWP species. Maximum likelihood analysis shows that many of the polymorphic codon sites are under mild positive selection. Of the fixed amino acid replacements, most have accumulated along the bindin lineage of E. lucunter. We analyzed the data with maximum likelihood models of variation in positive selection across lineages and codon sites, and with models that consider sites and lineages simultaneously. Our results show that positive selection is concentrated along the E. lucunter bindin lineage, and that codon sites with amino acid replacements fixed in this species show by far the highest signal of positive selection. Lineage-specific positive selection paralleling egg incompatibility provides support that adaptive evolution of sperm proteins acts to maintain recognition of bindin by changing egg receptors. Because both egg incompatibility and bindin divergence are greater between allopatric species than between sympatric species, the hypothesis of selection against hybridization (reinforcement) cannot explain why adaptive evolution has been confined to a single lineage in the American Echinometra. Instead, processes acting to varying degrees within species (e.g., sperm competition, sexual selection, and sexual conflict) are more promising explanations for lineage-specific positive selection on bindin.
Prognostic Significance of Diffuse Large B-Cell Lymphoma Cell of Origin Determined by Digital Gene Expression in Formalin-Fixed Paraffin-Embedded Tissue Biopsies
Authors: David W. Scott, Anja Mottok, Daisuke Ennishi, George W. Wright, Pedro Farinha, Susana Ben-Neriah, Robert Kridel, Garrett S. Barry, Christoffer Hother, Pau Abrisqueta, Merrill Boyle, Barbara Meissner, Adele Telenius, Kerry J. Savage, Laurie H. Sehn, Graham W. Slack, Christian Steidl, Louis M. Staudt, Joseph M. Connors, Lisa M. Rimsza, Randy D. Gascoyne
Journal: Journal of Clinical Oncology (2015)

To evaluate the prognostic impact of cell-of-origin (COO) subgroups, assigned using the recently described gene expression-based Lymph2Cx assay in comparison with International Prognostic Index (IPI) score and MYC/BCL2 coexpression status (dual expressers).Reproducibility of COO assignment using the Lymph2Cx assay was tested employing repeated sampling within tumor biopsies and changes in reagent lots. The assay was then applied to pretreatment formalin-fixed paraffin-embedded tissue (FFPET) biopsies from 344 patients with de novo diffuse large B-cell lymphoma (DLBCL) uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the British Columbia Cancer Agency. MYC and BCL2 protein expression was assessed using immunohistochemistry on tissue microarrays.The Lymph2Cx assay provided concordant COO calls in 96% of 49 repeatedly sampled tumor biopsies and in 100% of 83 FFPET biopsies tested across reagent lots. Critically, no frank misclassification (activated B-cell-like DLBCL to germinal center B-cell-like DLBCL or vice versa) was observed. Patients with activated B-cell-like DLBCL had significantly inferior outcomes compared with patients with germinal center B-cell-like DLBCL (log-rank P < .001 for time to progression, progression-free survival, disease-specific survival, and overall survival). In pairwise multivariable analyses, COO was associated with outcomes independent of IPI score and MYC/BCL2 immunohistochemistry. The prognostic significance of COO was particularly evident in patients with intermediate IPI scores and the non-MYC-positive/BCL2-positive subgroup (log-rank P < .001 for time to progression).Assignment of DLBCL COO by the Lymph2Cx assay using FFPET biopsies identifies patient groups with significantly different outcomes after R-CHOP, independent of IPI score and MYC/BCL2 dual expression.
A Phase I Trial of Vaccination of CA9-Derived Peptides for HLA-A24-Positive Patients with Cytokine-Refractory Metastatic Renal Cell Carcinoma
Authors: Hirotsugu Uemura, Kiyohide Fujimoto, Motoyoshi Tanaka, Motoyoshi Yoshikawa, Yoshihiko Hirao, Shigeya Uejima, Kazuhiro Yoshikawa, Kyogo Itoh
Journal: Clinical Cancer Research (2006)

A phase I peptide vaccination trial was done in patients with progressive cytokine-refractory metastatic renal cell carcinoma (RCC) to assess both the toxicity and capability to induce immune responses of three peptides (CA9p219-227, p288-296, and p323-331) derived from CA9, a tumor-associated antigen ubiquitously expressed in RCC.Twenty-three patients positive for human leukocyte antigen (HLA)-A24 with histologically confirmed RCC were enrolled. Eligibility included progressive disease after standard cytokine therapy with interleukin-2 and/or IFN-alpha. Patients were vaccinated s.c. with the three peptides emulsified in incomplete Freund's adjuvant at 2-week intervals. Pre- and post-vaccination blood samples were obtained for toxicity assessment and immunologic studies. Patients were monitored for clinical responses on a 3-monthly basis.Vaccinations were well tolerated without any major adverse event. Most of the patients developed peptide-specific CTLs and/or immunoglobulin G reactive to the peptides after the 6th or 9th vaccination, followed by a gradual increase in both CTL frequency and levels of peptide-reactive serum IgG. Three patients with multiple lung metastases showed partial responses with disappearance and shrinking of metastatic lesions. Additionally, stable disease for >6 months was observed in six patients (median duration, 12.2 months). Moreover, the median survival time of all patients who were progressive at trial enrollment after failing immunotherapy was 21.0 months (5-35 months).These results suggest that vaccination of these peptides is safe and recommended for further trials for HLA-A24-positive metastatic RCC patients.
The risk of developing Crohn's disease after an appendectomy: a population-based cohort study in Sweden and Denmark
Authors: G. G Kaplan, B. V Pedersen, R. E Andersson, B. E Sands, J. Korzenik, M. Frisch
Journal: Gut (2007)

The relationship between appendectomy and Crohn's disease is controversial. A Swedish-Danish cohort study was conducted to assess the risk of developing Crohn's disease after an appendectomy.709 353 appendectomy patients in Sweden (since 1964) and Denmark (since 1977) were followed for first hospitalisations for Crohn's disease to 2004. Standardised incidence ratios (SIR) served as relative risks.Overall, 1655 Crohn's disease cases were observed during 11.1 million person-years of follow-up. Whereas appendectomy before the age of 10 years was not associated with the risk of Crohn's disease (SIR 1.00; 95% CI 0.80-1.25), the overall SIR of developing Crohn's disease was 1.52 (95% CI 1.45-1.59), being highest in the first 6 months (SIR 8.69; 95% CI 7.68-9.84). SIR diminished rapidly thereafter, with the risk of Crohn's disease reaching background levels after 5-10 years for Crohn's disease overall, as well as for Crohn's ileitis, ileocolonic Crohn's disease, Crohn's colitis and other/unspecified Crohn's disease. A long-term increased risk of Crohn's disease up to 20 years after the appendectomy was seen only in appendectomy patients without appendicitis or mesenteric lymphadenitis.The transient increased risk of Crohn's disease after an appendectomy is probably explained by diagnostic bias.
Negative reports of mental health deter people from seeking help
Authors: Rebecca Coombes
Journal: BMJ (2006)

Negative reporting in the media of mental health problems stigmatises people who are most severely ill and prevents them seeking medical help, says a new survey of press coverage in England.

The survey concludes that, although common problems such as premenstrual tension receive sympathetic coverage, stories involving severe mental illness focus on the issue of public safety.

The survey, published …
rheumatoid factors in primary and reactive macroglobulinaemia.
Authors: F Klein, P Mattern
Journal: Annals of the Rheumatic Diseases (1965)

Theoccurrence of1gM(=/32m)-globulins capable ofreacting withIgG(= 7S-y)-globulin, thesocalled rheumatoid factors, isnotrestricted torheumatoid arthritis, buthasbeenreported inavariety ofconditions unrelated tothecollagen diseases. Theimportance ofthese false  reactions lies inthepossibility ofobtaining moreinformation abouttheorigin oftherheumatoid factors by studying different biological conditions underwhich these factors canarise. Manyofthediseases associated withfalse positive reactions inthetests forrheumatoid factors belong tothegroupofchronic infections. Thusa high incidence offalse positive reactions hasbeenreported insyphilis (Bloomfield, 1960), leprosy (Cathcart, Williams, Ross,andCalkins, 1961), kala-azar (Kunkel, Simon, andFudenberg, 1958), tuberculosis (Singer, Plotz, Peralta, andLyons, 1962) andchronic bronchitis (Bonomo, Tursi, and Pinto1963), although innoneofthese instances could this be confirmed byValkenburg andHijmans (unpublished). Theexperimental production ofrheumatoid factors byprolonged immunization withcertain bacteria byEyquem,Guyot-Jeannin, andPodliachouk(1959) andAbruzzo andChristian (1961), andwithpurified proteins either alone orincombination withtheir specific antibody (Ahoand Wager,1961)hasprovided somebasis forthe expectation that chronic infections could beaccompanied bythepresence ofrheumatoid factors. The explanation inallsuchcaseswouldthenbethat a prolonged stimulation withy-globulin whichis altered byitsbinding toanantigen, produces rheumatoid factors asantibodies against they-globulin partofimmunecomplexes. Aninteresting example issubacute bacterial endocarditis (Williams and Kunkel, 1962), inwhichtheantigen isbeing constantly fedinto thecirculation, asituation whichis analogous totheexperiments ofEyquemandothers (1959).
Preliminary Results Of a Phase II Study Of Single Agent Bay 80-6946, a Novel PI3K Inhibitor, In Patients With Relapsed/Refractory, Indolent Or Aggressive Lymphoma
Authors: Martin Dreyling, Franck Morschhauser, Dominique Bron, Krimo Bouabdallah, Umberto Vitolo, Kim Linton, Eric Van Den Neste, Silvia Mappa, Marius Giurescu, Barrett H. Childs, Pier Luigi Zinzani
Journal: Blood (2013)
71 HYPOXIA UP-REGULATES SERPIN B3 IN HEPATIC CANCER CELLS: A HIF-2 α ASSOCIATED EVENT RELATED TO INVASIVENESS AND EPITHELIAL TO MESENCHYMAL TRANSITION
Authors: S. Cannito, C. Turato, S. Quarta, C. Paternostro, T. Musso, E. David, S. Colombatto, A. Biasiolo, M. Villano, P. Pontisso, M. Parola
Journal: Journal of Hepatology (2010)
Factors influencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with long-term follow-up.
Authors: P P Rosen, S Groshen, D W Kinne, L Norton
Journal: Journal of Clinical Oncology (1993)

PURPOSE This study was undertaken to define prognostically favorable and unfavorable subgroups of node-negative breast carcinoma patients by employing conventional pathologic data. PATIENTS AND METHODS Seven hundred sixty-seven women with T1N0M0/T2N0M0 breast carcinoma treated consecutively from 1964 through 1970 by modified or radical mastectomy without systemic adjuvant therapy were analyzed at a median follow-up duration of 18 years. RESULTS Size and histologic type of the carcinoma were crucial discriminants of prognosis. We defined a prognostically favorable group of 219 patients (29%) with infiltrating duct or lobular carcinoma &lt; or = 1.0 cm in diameter or special tumor types &lt; or = 3.0 cm. This group had a relapse-free survival rate of 91% at 10 years and 87% at 20 years. The less favorable group (548 patients, 71%) with infiltrating duct or lobular carcinoma greater than 1.0 cm and special tumor types greater than 3.0 cm had relapse-free survival rates of 73% and 68% at 10 and 20 years, respectively. The frequency of nonmammary malignant neoplasms (NMMN) was similar to that of contralateral carcinoma. Deaths due to NMMN were seven times more frequent than deaths due to contralateral carcinoma. CONCLUSION Nearly 30% of these node-negative patients, identified on the basis of tumor size and type, had an extremely favorable prognosis. There is insufficient evidence to warrant the routine use of adjuvant therapy in this group unless new forms of treatment prove to be less toxic and/or more effective in enhancing relapse-free survival. Early detection of NMMN should be an important part of the follow-up of node-negative breast carcinoma patients.
Bacterial toxins and the immune system
Authors: Jorge E. Galán
Journal: The Journal of Experimental Medicine (2005)

Microorganisms that cause persistent infection often exhibit specific adaptations that allow them to avoid the adaptive immune response. Recently, several bacterial toxins have been shown in vitro to disrupt immune cell functions. However, it remains to be established whether these activities are relevant during infection and whether these toxins have specifically evolved to disrupt the adaptive immune system.
Upper airway inflammation in children exposed to ambient ozone and potential signs of adaptation
Authors: M.V. Kopp, C. Ulmer, G. Ihorst, H.H. Seydewitz, T. Frischer, J. Forster, J. Kuehr
Journal: European Respiratory Journal (1999)

In order to investigate nasal inflammation and subsequent adaptation after ambient ozone exposure, nasal lavage (NL) fluid was collected from 170 schoolchildren on 11 occasions (time points) between March and October. Eosinophil cationic protein (ECP), albumin and leukocytes were quantified as markers of nasal inflammation. The highest half-hour outdoor O3 concentration for each individual on the day prior to the NL was used as a measure of exposure (O3indiv). To avoid confounding with exposure to common environmental allergens, the study population was restricted to children without sensitization to inhalant allergens. In the initial period of increased O3 levels in May (time point 4), with a median O3indiv of 135 microg x m(-3) (5th-95th percentile 100-184 microg x m(-3)), the highest medians of all 11 leukocyte and ECP measurements were observed. The highest O3indiv were observed in June at time point 7 (O3indiv 173 microg x m(-3), 5th-95th percentile 120-203 microg x m(-3)). Cross-sectional analysis of all 11 time points revealed no significant association of O3indiv on the one hand and ECP, albumin and leukocyte levels on the other. A multivariable model estimated using generalized estimating equations showed a statistically significant association of O3indiv and leukocytes and ECP as the dependent variable, when time points 1-4 were analysed (p&lt;0.05). In the same model, this association diminished continuously when time points 5-11 were added stepwise, in spite of high O3 exposure. Not even a tendency towards an O3 effect could be recognized when time points 1-8 were considered. The results indicate: 1) acute inflammation of the nasal mucosa after the first increase in ambient ozone levels, with 2) a significant dose-dependent increase in leukocyte and eosinophil cationic protein levels, and 3) possible adaptation of the nasal mucosa in spite of constant high levels of ozone exposure in children during the summer season.
In the Spotlight: Biomedical Imaging
Authors: Andrew F. Laine
Journal: IEEE Reviews in Biomedical Engineering (2011)

In this review, we will focus on advances in several imaging modalities, and their relationships to specific disease states. In the first section we discuss the role of 4-D ultrasound in estimating cardiac function, and how such information may be combined with additional data for assessment of ischemia. Section II describes the role of multimodal imaging and segmentation in computer-aided treatment planning for liver cancer. In Section III, we explore new methodologies in the fusion of PET data with complementary images from MRI and CT, with applications in the leading types of cancer. Finally, in Section IV, recent advances in measuring cerebral blood volume are described.