tbuckley/cabot-search huggingface dataset:
Thymic selection pathway regulates the effector function of CD4 T cells
Authors: Wei Li, M. Hanief Sofi, Norman Yeh, Sarita Sehra, Brian P. McCarthy, Dipak R. Patel, Randy R. Brutkiewicz, Mark H. Kaplan, Cheong-Hee Chang
Journal: The Journal of Experimental Medicine (2007)

Recently, a new developmental pathway for CD4 T cells that is mediated by major histocompatibility complex class II–positive thymocytes was identified (Choi, E.Y., K.C. Jung, H.J. Park, D.H. Chung, J.S. Song, S.D. Yang, E. Simpson, and S.H. Park. 2005. Immunity. 23:387–396; Li, W., M.G. Kim, T.S. Gourley, B.P. McCarthy, D.B. Sant'angelo, and C.H. Chang. 2005. Immunity. 23:375–386). We demonstrate that thymocyte-selected CD4 (T-CD4) T cells can rapidly produce interferon γ and interleukin (IL) 4 upon in vivo and in vitro T cell receptor stimulation. These T-CD4 T cells appear to be effector cells producing both T helper type 1 (Th1) and Th2 cytokines, and they maintain a potential to produce Th2 cytokines under Th1-skewing conditions in a signal transducer and activator of transcription 6–independent manner. The IL-4 mRNA level is high in CD4 single-positive thymocytes if they are selected on thymocytes, which is at least partly caused by enhanced histone acetylation of the IL-4 locus. However, mice that can generate T-CD4 T cells showed attenuated immune responses in an allergen-induced airway inflammation model, suggesting a protective role for T-CD4 T cells during an airway challenge. Our results imply that this thymic selection pathway plays an important role in determining the effector function of the resulting CD4 cells and in regulating immune response.
Long-term Stability of Remission in Nephrotic Syndrome after Treatment with Cyclophosphamide
Authors: J. S. Cameron, C. Chantler, C. S. Ogg, R. H. R. White
Journal: BMJ (1974)

Fifty-eight children with minimal-change nephrotic lesions who relapsed repeatedly and showed toxic side effects from corticosteroids were treated with cyclophosphamide for an average of 12 weeks. The initial dose was 5 mg/kg/day. Four to seven years (mean 5.8 years) later 20 remained in remission, 34 were still relapsing, and 4 had died (two during relapses, one of measles after cyclophosphamide, and one of a brain-stem astrocytoma). The half time for the relapse-free period after treatment was 2.8 years. There was no relationship between the length of treatment with cyclophosphamide and the stability of remission within the limits studied.
290 INSULIN RESISTANCE PREDICTS RISK FOR THE DEVELOPMENT OF VARICEAL BLEEDING
Authors: M. Jover, L. Grande, I. Camacho, B. Pardo, B. Figueruela, A. Madrazo, C. Ortiz, D. Sanchez, P. Guerrero, E. Suarez, J.L. Larraona, M. Romero-Gomez
Journal: Journal of Hepatology (2008)
Activation of Signal Transducer and Activator of Transcription-5 in Prostate Cancer Predicts Early Recurrence
Authors: Hongzhen Li, Ying Zhang, Andrew Glass, Tobias Zellweger, Edmund Gehan, Lukas Bubendorf, Edward P. Gelmann, Marja T. Nevalainen
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We have shown previously that the signal transducer and activator of transcription-5 (Stat5) is a critical survival factor in human prostate cancer cells. In addition, we recently showed that Stat5 is activated at a high level, particularly in high-grade human prostate cancers. Here, we investigated whether activation of Stat5 in prostate cancer was linked to clinical outcome with disease recurrence as end point. Experimental Design: Immunohistochemistry was used to detect active, nuclear Stat5 in 357 paraffin-embedded prostate cancer specimens on a tissue microarray with clinical follow-up data. Stat5 activation status in prostate cancer specimens was analyzed by univariate and multivariate survival analysis to determine whether activation of Stat5 predicts earlier prostate cancer recurrence. Separate sets of statistical analysis were done for all patients regardless of Gleason grade and for patients with prostate cancer of intermediate Gleason grades (3 and 4). Results and Conclusions: Stat5 activation in prostate cancer was associated with early disease recurrence (P = 0.0399). Importantly, active Stat5 also predicted shorter progression-free survival in intermediate Gleason grade prostate cancers (P = 0.0409). Stat5 activation remained an independent prognostic marker after adjusting for Gleason grade, pT stage, perineural invasion, or seminal vesicle infiltration in all patients (P = 0.0565) and in Gleason grade 3 or 4 patients (P = 0.0582). The results of this work also confirmed our previous finding of association of Stat5 activation with a high histologic grade of prostate cancer (R = 0.11, P = 0.033). In summary, our study shows that active Stat5 distinguished prostate cancer patients whose disease is likely to progress earlier; therefore, active Stat5 may be a useful marker for selection of more individualized treatment. The results of this study need to be validated in a large prospective cohort.
Epigenetic Specificity of Loss of Imprinting of the IGF2 Gene in Wilms Tumors
Authors: Hans T. Bjornsson, Lindsey J. Brown, M. Danielle Fallin, Michael A. Rongione, Marina Bibikova, Eliza Wickham, Jian-Bing Fan, Andrew P. Feinberg
Journal: JNCI Journal of the National Cancer Institute (2007)

Loss of imprinting (LOI) of the IGF2 gene (which encodes insulin-like growth factor II) is the most common genetic or epigenetic alteration in Wilms tumor; LOI involves aberrant activation of the normally repressed maternally inherited allele. We found previously that LOI of IGF2 occurs in approximately half of all Wilms tumors (i.e., those arising from lineage-committed nephrogenic progenitor cells). We investigated whether LOI of IGF2 is associated with relaxation of imprinting at loci other than IGF2 or with widespread alterations in DNA methylation. We stratified 59 Wilms tumor samples by IGF2 LOI status by use of hot-stop reverse transcription-polymerase chain reaction and/or methylation analysis of the differentially methylated region of the H19 gene and identified 31 samples with and 28 without LOI. We used quantitative allele-specific expression analysis to determine whether six other imprinted genes (i.e., H19, KCNQ1, LIT1, TSSC5, GRB10, and MEG3) had subtle LOI. No statistically significant difference in allele-specific expression between Wilms tumor with or without LOI was found for LIT1, TSSC5, GRB10, and MEG3. For the KCNQ1 gene there was a slight difference between the groups with (37.0%, 95% confidence interval [CI] = 31.8% to 42.2%) and without (27.7%, 95% CI = 21.8% to 33.5%) LOI (P = .02 for F test of group differences in a mixed-effects model). For H19, we also found a slight difference between the groups with (7.5%, 95% CI = 2.4% to 12.7%) and without (2.2%, 95% CI = -3.2% to 7.6%) LOI of IGF2 (P = .15 for F test). In 27 tumor samples, we also used a microarray technique to analyze methylation of 378 genes, 38 of which were suspected or confirmed imprinted genes. We found that statistically significant alterations in only the differentially methylated region of the H19 gene were associated with LOI of IGF2. Thus, epigenetic alterations in Wilms tumors are not widespread, supporting the gene and lineage specificity of LOI of IGF2.
Comparison of Gonioscopy and Anterior Segment Ocular Coherence Tomography in Detecting Angle Closure in Different Quadrants of the Anterior Chamber Angle
Authors: Lisandro M. Sakata, Raghavan Lavanya, David S. Friedman, Han T. Aung, Hong Gao, Rajesh S. Kumar, Paul J. Foster, Tin Aung
Journal: Ophthalmology (2007)
Overexpression of CCL-21/secondary lymphoid tissue chemokine in human dendritic cells augments chemotactic activities for lymphocytes and antigen presenting cells.
Authors: Karen Riedl, Felicita Baratelli, Raj K Batra, Seok Yang, Jie Luo, Brian Escuadro, Robert Figlin, Robert Strieter, Sherven Sharma, Steven Dubinett
Journal: Molecular Cancer (2003)

Ex vivo generated dendritic cells (DC) genetically modified to express secondary lymphoid tissue chemokine (CCL-21/SLC) have been shown to stimulate potent antitumor responses in murine models. When injected intratumorally, CCL-21 colocalizes DC and lymphocyte effector cells at the tumor site. This may improve tumor antigen presentation and T cell activation by utilizing the tumor as an in vivo source of antigen for DC. In order to develop DC-based cancer therapies for intratumoral injection that could promote tumor antigen uptake and presentation in situ, we constructed and characterized an adenoviral vector that expresses human CCL-21 (AdCCL-21). Human monocyte derived DC were cultured in GM-CSF and IL-4 for 6 days. Following AdCCL-21 transduction, CCL-21 protein production was assessed by ELISA on day 8. DC transduced with AdCCL-21 at multiplicities of infection (MOIs) of 50:1 or 100:1 produced up to 210 ± 9 ng/ml and 278 ± 6.5 ng/ml /106 cells/48 hours, respectively. Following transduction, an immature DC phenotype was maintained and an upregulation of the costimulatory molecule, CD86 was noted. In addition, supernatant from AdCCL-21-DC caused significant chemotaxis of peripheral blood lymphocytes and mature DC. These studies demonstrate that AdCCL-21-DC generate functional levels of CCL-21 without adversely altering DC phenotype. These findings strengthen the rationale for further investigation of AdCCL-21-DC as a DC-based therapy in cancer treatment.
Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages
Authors: Yuichiro Hisatomi, Kenji Okumura, Kimitoshi Nakamura, Shirou Matsumoto, Ayumi Satoh, Koji Nagano, Tetsuro Yamamoto, Fumio Endo
Journal: Hepatology (2004)

Experimental injury is useful to induce tissue stem cells, which may exist in small numbers under normal conditions. The salivary glands originate from the endoderm and consist of acinar and ductal epithelial cells, which have exocrine function. After salivary gland duct ligation, acinar cells disappear as a result of apoptosis, and duct epithelium subsequently proliferates. In this study, we analyzed the tissue stem cells induced by salivary gland duct ligation in mice using immunohistochemistry and flow cytometry. We sorted the Sca-1 + /c-Kit + fraction from adult mice salivary glands by way of fluorescence-activated cell sorting. The sorted cells were apparently homogeneous and were designated mouse salivary gland-derived progenitors (mSGPs). mSGP cells differentiated into a hepatic lineage when cultured in matrigel. In spherical culture in the presence of glucagon-like peptide-1 (GLP-1), these cells differentiated into a pancreatic endocrine lineage. When spheroidal bodies of mSGP, 20 to 30 μm in diameter, were transplanted into liver via the portal vein, the cells integrated into hepatic cords and expressed albumin and α1-antitrypsin, suggesting that they had differentiated into hepatic-type cells. Moreover, ductlike structures formed by mSGP cells also appeared, epithelial cells of which were positive for cytokeratin 19. In conclusion, fluorescence-activated cell sorting (FACS) based on histologic evidence is efficient in isolating adult tissue stem cells of the salivary gland. Tissue stem cells of endodermal origin ( e.g. , hepatic oval cells, pancreatic epithelial progenitor cells, and salivary gland progenitor cells) have similarities in their molecular markers and tissue location. Our findings suggest the existence of common tissue stem cells in endoderm-derived organs. (Hepatology 2004;39:667-675.)
Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo.
Authors: A L Angiolillo, C Sgadari, D D Taub, F Liao, J M Farber, S Maheshwari, H K Kleinman, G H Reaman, G Tosato
Journal: The Journal of Experimental Medicine (1995)

Human interferon-inducible protein 10 (IP-10), a member of the alpha chemokine family, inhibits bone marrow colony formation, has antitumor activity in vivo, is chemoattractant for human monocytes and T cells, and promotes T cell adhesion to endothelial cells. Here we report that IP-10 is a potent inhibitor of angiogenesis in vivo. IP-10 profoundly inhibited basic fibroblast growth factor-induced neovascularization of Matrigel (prepared by H. K. Kleinman) injected subcutaneously into athymic mice. In addition, IP-10, in a dose-dependent fashion, suppressed endothelial cell differentiation into tubular capillary structures in vitro. IP-10 had no effect on endothelial cell growth, attachment, and migration as assayed in vitro. These results document an important biological property of IP-10 and raise the possibility that IP-10 may participate in the regulation of angiogenesis during inflammation and tumorigenesis.
Prevalence of Angina in Women Versus Men
Authors: Harry Hemingway, Claudia Langenberg, Jacqueline Damant, Chris Frost, Kalevi Pyörälä, Elizabeth Barrett-Connor
Journal: Circulation (2008)

In the absence of previous international comparisons, we sought to systematically evaluate, across time and participant age, the sex ratio in angina prevalence in countries that differ widely in the rate of mortality due to myocardial infarction.We searched MEDLINE and EMBASE until February 2006 for healthy population studies published in any language that reported the prevalence of angina (Rose questionnaire) in women and men. We obtained myocardial infarction mortality rates from the World Health Organization. A total of 74 reports of 13,331 angina cases in women and 11,511 cases in men from 31 countries were included. Angina prevalence varied widely across populations, from 0.73% to 14.4% (population weighted mean 6.7%) in women and from 0.76% to 15.1% (population weighted mean 5.7%) in men, and was strongly correlated within populations between the sexes (r=0.80, P<0.0001). Angina prevalence showed a small female excess with a pooled random-effects sex ratio of 1.20 (95% CI 1.14 to 1.28, P<0.0001). This female excess was found across countries with widely differing myocardial infarction mortality rates in women (interquartile range 12.7 to 126.5 per 100,000), was particularly high in the American studies (1.40, 95% CI 1.28 to 1.52), and was higher among nonwhite ethnic groups than among whites. This sex ratio did not differ significantly by participant's age, the year the survey began, or the sex ratio for mortality due to myocardial infarction.Over time and at different ages, independent of diagnostic and treatment practices, women have a similar or slightly higher prevalence of angina than men across countries with widely differing myocardial infarction mortality rates.
Somatic hypermutation of an immunoglobulin mu heavy chain transgene.
Authors: J Sohn, R M Gerstein, C L Hsieh, M Lemer, E Selsing
Journal: The Journal of Experimental Medicine (1993)

We have analyzed somatic hypermutation of an immunoglobulin (Ig) heavy chain transgene. Hybridomas expressing the transgene were produced from immunized transgenic mice and transgene copies were sequenced to assay for mutation. In two IgM-producing hybridomas, as well as in several IgG-producing hybridomas, mutations were found in the VDJ region of the transgene. In the IgM-producing hybridomas, both mutated and unmutated transgene copies were present and expressed as mRNA. Several mutated transgene copies were present in a single cell and these showed different patterns of mutation. Two IgG-producing hybridomas isolated from a single animal also showed a hierarchical pattern of mutation indicating that transgene mutations can accumulate during B cell proliferation, similar to the mutational process for endogenous antibody genes. Among hybridomas that expressed both IgG and IgM molecules derived from the transgene, the isotype-switched gamma transgene copy exhibited a higher level of mutation than the mu transgene copies. Our results indicate that the 15-kb ARSmu transgene contains all the sequence information required to target the Ig-specific hypermutational machinery, and raise the possibility that sequences associated with the endogenous CH locus might enhance somatic mutation.
PALMAR AND PLANTAR SEED KEEATOSES AND INTEENAL MALIGNANCY
Authors: E. L. RHODES
Journal: British Journal of Dermatology (1970)

Journal Article PALMAR AND PLANTAR SEED KEEATOSES AND INTEENAL MALIGNANCY Get access E. L. RHODES E. L. RHODES Department of Dermatology, Kingston Hospital and St Helier Hospital, Surrey, England Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 82, Issue 4, 1 April 1970, Pages 361–363, https://doi.org/10.1111/j.1365-2133.1970.tb06833.x Published: 01 April 1970
In vivo inhibition of the antibody response by a complement receptor-specific monoclonal antibody.
Authors: B Heyman, E J Wiersma, T Kinoshita
Journal: The Journal of Experimental Medicine (1990)

BALB/c mice were injected intravenously with three different monoclonal antibodies (mAbs) specific for complement receptor 1 (CR1). Two of the mAbs crossreacted with CR2. 24 h later, the mice were immunized with horse erythrocytes or keyhole limpet hemocyanin (KLH), and the primary antibody response was measured. One of the anti-CR antibodies, 7G6, suppressed greater than 99% of the direct plaque-forming cell response against horse red blood cells (HRBC). The same antibody markedly suppressed the serum antibody responses to both HRBC and KLH. To be optimally suppressive, the mAb had to be injected before suboptimal concentrations of antigen. The other two complement receptor-specific antibodies had very moderate, if any, effects on the antibody response. 7G6 was able to downregulate CR1 and CR2 on the surface of B cells and, in addition, to inhibit rosette formation with C3d-coated sheep erythrocytes (EC3d). One of the antibodies with a weak effect downregulated only CR1. The other downregulated both CR1 and CR2, although not as efficiently as 7G6, and was unable to inhibit EC3d rosette formation. We conclude that the reason 7G6 is outstanding in its suppressive capacity is that it is the only mAb tested that functionally blocks CR2. The data suggest that CR2 is of crucial importance in the initiation of a normal antibody response to physiological concentrations of antigen.
Giant cell glioblastoma: A glioblastoma subtype with distinct epidemiology and superior prognosis
Authors: Kevin R. Kozak, John S. Moody
Journal: Neuro-Oncology (2009)

Giant cell glioblastoma (GC) is an uncommon subtype of glioblastoma multiforme (GBM). Consequently, the epidemiology, natural history, and factors associated with outcome are not well defined. Patients diagnosed with GC from 1988 through 2004 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Outcomes were examined with Kaplan-Meier survival analysis and Cox models. For comparison, similar analyses were conducted for patients diagnosed with GBM. GC was identified in 1% of 16,430 patients diagnosed with either GC or GBM. Compared with GBM, GC showed similar gender and racial distributions. Likewise, tumor size and location were not significantly different between the two histologies. GC tended to occur in younger patients with a median age at diagnosis of 51 years, compared with 62 years for GBM. Additionally, patients with GC were more likely to undergo complete resection compared with patients with GBM. For both histologies, young age, tumor size, extent of resection, and the use of adjuvant radiation therapy (RT) were associated with improved survival. Cox modeling suggests the prognosis for GC is significantly superior to that for GBM (hazard ratio = 0.76; 95% confidence interval, 0.59-0.97) even after adjustment for factors affecting survival. GC is an uncommon GBM subtype that tends to occur in younger patients. Prospective data defining optimal treatment for GC are unavailable; however, these retrospective findings suggest that resection, as opposed to biopsy only, and adjuvant RT may improve survival. The prognosis of GC is superior to that of GBM, and long-term survival is possible, suggesting aggressive therapy is warranted.
PARP inhibition delays transition of hypertensive cardiopathy to heart failure in spontaneously hypertensive rats
Authors: E. Bartha, I. Solti, L. Kereskai, J. Lantos, E. Plozer, K. Magyar, E. Szabados, T. Kalai, K. Hideg, R. Halmosi, B. Sumegi, K. Toth
Journal: Cardiovascular Research (2009)

Aims Oxidative stress followed by abnormal signalling can play a critical role in the development of long-term, high blood pressure-induced cardiac remodelling in heart failure (HF).Since oxidative stress-induced poly(ADP-ribose)polymerase (PARP) activation and cell death have been observed in several experimental models, we investigated the possibility that inhibition of nuclear PARP improves cardiac performance and delays transition from hypertensive cardiopathy to HF in a spontaneously hypertensive rat (SHR) model of HF.Methods and results SHRs were divided into two groups: one received no treatment (SHR-C) and the other (SHR-L) received 5 mg/kg/day L-2286 (PARP-inhibitor) orally for 46 weeks.A third group was a normotensive age-matched control group (CFY) and a fourth was a normotensive age-matched group receiving L-2286 treatment 5 mg/kg/day (CFY+L).At the beginning of the study, systolic function was similar in both CFY and SHR groups.In the SHR-C group at the end of the study, eccentric hypertrophy with poor left ventricular (LV) systolic function was observed, while PARP inhibitor treatment preserved systolic LV function.Due to these favourable changes, the survival rate of SHRs was significantly improved (P , 0.01) by the administration of the PARP inhibitor (L-2286).The PARP inhibitor used did not affect the elevated blood pressure of SHR rats, but moderated the level of plasma-BNP (P , 0.01) and favourably influenced all the measured gravimetric parameters (P , 0.05) and the extent of myocardial fibrosis (P , 0.05).The inhibition of PARP increased the phosporylation of Akt-1/GSK-3b (P , 0.01), ERK 1/2 (P , 0.01), and PKC 1 (P , 0.01), and decreased the phosphorylation of JNK (P , 0.05), p-38 MAPK (P , 0.01), PKC pan bII and PKC z/l (P , 0.01), and PKC a/bII and d (P , 0.05).Conclusion These data demonstrate that chronic inhibition of PARP induces long-term favourable changes in the most important signalling pathways related to oxidative stress.PARP inhibition also prevents remodelling, preserves systolic function, and delays transition of hypertensive cardiopathy to HF in SHRs.