tbuckley/cabot-search huggingface dataset:
Reversal of Proinflammatory Responses by Ligating the Macrophage Fcγ Receptor Type I
Authors: Fayyaz S. Sutterwala, Gary J. Noel, Padmini Salgame, David M. Mosser
Journal: The Journal of Experimental Medicine (1998)

Macrophages can respond to a variety of infectious and/or inflammatory stimuli by secreting an array of proinflammatory cytokines, the overproduction of which can result in shock or even death. In this report, we demonstrate that ligation of macrophage Fcγ receptors (FcγR) can lead to a reversal of macrophage proinflammatory responses by inducing an upregulation of interleukin (IL)-10, with a reciprocal inhibition of IL-12 production. IL-10 upregulation was specific to FcγR ligation, since the ligation of the Mac-1 receptor did not alter IL-10 production. The identification of the specific FcγR subtype responsible for IL-10 upregulation was determined in gene knockout mice. Macrophages from mice lacking the FcR γ chain, which is required for assembly and signaling by FcγRI and FcγRIII, failed to upregulate IL-10 in response to immune complexes. However, mice lacking either the FcγRII or the FcγRIII were fully capable of upregulating IL-10 production, implicating FcγRI in this process. The biological consequences of FcγRI ligation were determined in both in vitro and in vivo models of inflammation and sepsis. In all of the models tested, the ligation of FcγR promoted the production of IL-10 and inhibited the secretion of IL-12. This reciprocal alteration in the pattern of macrophage cytokine production illustrates a potentially important role for FcγR-mediated clearance in suppressing macrophage proinflammatory responses.
A case of proteasome-associated auto-inflammatory syndrome with compound heterozygous mutations
Authors: Amelia McDermott, Adriana Almeida Jesus, Yin Liu, Peter Kim, Jennifer Jacks, Gina A. Montealegre Sanchez, Yongqing Chen, Aarthi Kannan, Alicia Schnebelen, Peter D. Emanuel, Sara Shalin, Kim Hiatt, Raphaela Goldbach-Mansky, Ling Gao
Journal: Journal of the American Academy of Dermatology (2013)
Serial studies on in vitro colony formation in patients with acute leukemia in relation to the maintenance of remission
Authors: Kazuo Kubota, Hideaki Mizoguchi, Yasusada Miura, Shin Chiyoda, Yoshitomo Muto, Fumimaro Takaku
Journal: American Journal of Hematology (1978)

For the purpose of preventing a relapse of acute leukemia which is currently the major problem in the successful treatment of the disease, repeated consolidation or intensification therapy during the first year following remission is important. To evaluate these therapies, we investigated the serial changes in CFU-C's of the marrow cells from 12 patients with acute nonlymphocytic leukemia in remission and tried to estimate the relationship between the intensity of consolidation or intensification therapy and the duration of remission, utilizing the degree of reduction in CFU-C's seven days after these treatments as an indicator. As a result, after 21 out of 22 courses of therapy where CFU-C's were reduced significantly after the therapy, the patients were still in remission at the time of the next intensificiation therapy (at most for about 100 days). On the other hand, after five out of ten courses where CFU-C's were not reduced significantly, the patients were in relapse at the time of the next intensification therapy. From these results, it may be inferred that cases whose CFU-C's are not reduced significantly should be treated intensively again within a short period.
Defining a "Patients' Bill of Rights" for the Next CenturyON THE COVERA Patients' Bill of Rights: The Medical Student's RolePatients' Rights Proposals: The Insurers' PerspectiveAmerican Independence and the Right to Emergency CareGoing Hollywood With Patient Rights in Managed CarePhysician-Legislators: Physicians Practicing Public Service
Authors: S C Weiss
Journal: JAMA (1999)

As the millennium approaches, the health care delivery system in the United States remains in a period of transformation. The commercialization of medicine has challenged the professional dominance of physicians.
Epidermal Growth Factor Receptor Regulates Aberrant Expression of Insulin-Like Growth Factor-Binding Protein 3
Authors: Munenori Takaoka, Hideki Harada, Claudia D. Andl, Kenji Oyama, Yoshio Naomoto, Kelly L. Dempsey, Andres J. Klein-Szanto, Wafik S. El-Deiry, Adda Grimberg, Hiroshi Nakagawa
Journal: Cancer Research (2004)

Epidermal growth factor receptor (EGFR) is frequently overexpressed in esophageal carcinoma and its precursor lesions. To gain insights into how EGFR overexpression affects cellular functions in primary human esophageal cells, we performed gene expression profiling and identified insulin-like growth factor-binding protein (IGFBP)-3 as the most up-regulated gene. IGFBP-3 regulates cell proliferation through both insulin-like growth factor-dependent and independent mechanisms. We found that IGFBP-3 mRNA and protein expression was increased in EGFR-overexpressing primary and immortalized human esophageal cells. IGFBP-3 was also up-regulated in EGFR-overexpressing cells in organotypic culture and in EGFR transgenic mice. Furthermore, IGFBP-3 mRNA was overexpressed in 80% of primary esophageal squamous cell carcinomas and 60% of primary esophageal adenocarcinomas. Concomitant up-regulation of EGFR and IGFBP-3 was observed in 60% of primary esophageal squamous cell carcinomas. Immunohistochemistry revealed cytoplasmic localization of IGFBP-3 in the preponderance of preneoplastic and neoplastic esophageal lesions. IGFBP-3 was also overexpressed in esophageal cancer cell lines at both mRNA (60%) and protein (40%) levels. IGFBP-3 secreted by cancer cells was capable of binding to insulin-like growth factor I. Functionally, epidermal growth factor appeared to regulate IGFBP-3 expression in esophageal cancer cell lines. Finally, suppression of IGFBP-3 by small interfering RNA augmented cell proliferation, suggesting that IGFBP-3 may inhibit tumor cell proliferation as a negative feedback mechanism. In aggregate, we have identified for the first time that IGFBP-3 is an aberrantly regulated gene through the EGFR signaling pathway and it may modulate EGFR effects during carcinogenesis.
The Complete Nucleotide Sequence of the Mitochondrial DNA of the Agnathan Lampetra fluviatilis: Bearings on the Phylogeny of Cyclostomes
Authors: Christiane Delarbre, Hector Escriva, Cyril Gallut, Véronique Barriel, Philippe Kourilsky, Philippe Janvier, Vincent Laudet, Gabriel Gachelin
Journal: Molecular Biology and Evolution (2000)

There are two competing theories about the interrelationships of craniates: the cyclostome theory assumes that lampreys and hagfishes are a clade, the cyclostomes, whose sister group is the jawed vertebrates (gnathostomes); the vertebrate theory assumes that lampreys and gnathostomes are a clade, the vertebrates, whose sister group is hagfishes. The vertebrate theory is best supported by a number of unique anatomical and physiological characters. Molecular sequence data from 18S and 28S rRNA genes rather support the cyclostome theory, but mtDNA sequence of Myxine glutinosa rather supports the vertebrate theory. Additional molecular data are thus needed to elucidate this three-taxon problem. We determined the complete nucleotide sequence of the mtDNA of the lamprey Lampetra fluviatilis. The mtDNA of L. fluviatilis possesses the same genomic organization as Petromyzon marinus, which validates this gene order as a synapomorphy of lampreys. The mtDNA sequence of L. fluviatilis was used in combination with relevant mtDNA sequences for an approach to the hagfish/lamprey relationships using the maximum-parsimony, neighbor-joining, and maximum-likelihood methods. Although trees compatible with our present knowledge of the phylogeny of craniates can be reconstructed by using the three methods, the data collected do not support the vertebrate or the cyclostome hypothesis. The present data set does not allow the resolution of this three-taxon problem, and new kinds of data, such as nuclear DNA sequences, need to be collected.
Virus infections and sports performance--a prospective study.
Authors: J A Roberts, J A Wilson, G B Clements
Journal: British Journal of Sports Medicine (1988)

There are numerous anecdotal reports relating infection to deterioration in sporting performance. Unexplained failures by top sportsmen are often attributed to recent or current infections. We have carried out a prospective investigation to determine the effect of viral infections on the performance of a group of 68 elite track and field athletes. Athletes were monitored for evidence of viral infection during winter training and their form was assessed subjectively and also semi-objectively by analogue scale questionnaires. Static elevated titres of neutralising antibody to Coxsackie B 1-5 were present in 54% of the athletes and 79% had serological evidence of past viral infection. The raised titres did not relate to poor performance. There was no evidence that loss of form was related to subclinical infection. Elevated antibody levels to Coxsackie B and other common viruses should be interpreted with great caution when assessing athletes complaining of poor performance.
Altered Cytoplasmic-to-Nuclear Ratio of Survivin Is a Prognostic Indicator in Breast Cancer
Authors: Donal J. Brennan, Elton Rexhepaj, Sallyann L. O'Brien, Elaine McSherry, Darran P. O'Connor, Ailís Fagan, Aedín C. Culhane, Desmond G. Higgins, Karin Jirstrom, Robert C. Millikan, Goran Landberg, Michael J. Duffy, Stephen M. Hewitt, William M. Gallagher
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Survivin (BIRC5) is a promising tumor biomarker. Conflicting data exist on its prognostic effect in breast cancer. These data may at least be partly due to the manual interpretation of immunohistochemical staining, especially as survivin can be located in both the nucleus and cytoplasm. Quantitative determination of survivin expression using image analysis offers the opportunity to develop alternative scoring models for survivin immunohistochemistry. Here, we present such a model. Experimental Design: A breast cancer tissue microarray containing 102 tumors was stained with an anti-survivin antibody. Whole-slide scanning was used to capture high-resolution images. These images were analyzed using automated algorithms to quantify the staining. Results: Increased nuclear, but not cytoplasmic, survivin was associated with a reduced overall survival (OS; P = 0.038) and disease-specific survival (P = 0.0015). A high cytoplasmic-to-nuclear ratio (CNR) of survivin was associated with improved OS (P = 0.005) and disease-specific survival (P = 0.05). Multivariate analysis revealed that the survivin CNR was an independent predictor of OS (hazard ratio, 0.09; 95% confidence interval, 0.01-0.76; P = 0.027). A survivin CNR of &amp;gt;5 correlated positively with estrogen receptor (P = 0.019) and progesterone receptor (P = 0.033) levels, whereas it was negatively associated with Ki-67 expression (P = 0.04), p53 status (P = 0.005), and c-myc amplification (P = 0.016). Conclusion: Different prognostic information is supplied by nuclear and cytoplasmic survivin in breast cancer. Nuclear survivin is a poor prognostic marker in breast cancer. Moreover, CNR of survivin, as determined by image analysis, is an independent prognostic factor.
Human skin cells support thymus-independent T cell development
Authors: R. A. Clark
Journal: Journal of Clinical Investigation (2005)

Thymic tissue has previously been considered a requirement for the generation of a functional and diverse population of human T cells. We report that fibroblasts and keratinocytes from human skin arrayed on a synthetic 3-dimensional matrix support the development of functional human T cells from hematopoietic precursor cells in the absence of thymic tissue. Newly generated T cells contained T cell receptor excision circles, possessed a diverse T cell repertoire, and were functionally mature and tolerant to self MHC, indicating successful completion of positive and negative selection. Skin cell cultures expressed the AIRE, Foxn1, and Hoxa3 transcription factors and a panel of autoantigens. Skin and bone marrow biopsies can thus be used to generate de novo functional and diverse T cell populations for potential therapeutic use in immunosuppressed patients.
The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel
Authors: Ahmed Ashour Ahmed, Anthony D. Mills, Ashraf E.K. Ibrahim, Jillian Temple, Cherie Blenkiron, Maria Vias, Charlie E. Massie, N. Gopalakrishna Iyer, Adam McGeoch, Robin Crawford, Barbara Nicke, Julian Downward, Charles Swanton, Stephen D. Bell, Helena M. Earl, Ronald A. Laskey, Carlos Caldas, James D. Brenton
Journal: Cancer Cell (2007)
The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression
Authors: Jean-Philippe Coppé, Pierre-Yves Desprez, Ana Krtolica, Judith Campisi
Journal: Annual Review of Pathology Mechanisms of Disease (2010)

Cellular senescence is a tumor-suppressive mechanism that permanently arrests cells at risk for malignant transformation. However, accumulating evidence shows that senescent cells can have deleterious effects on the tissue microenvironment. The most significant of these effects is the acquisition of a senescence-associated secretory phenotype (SASP) that turns senescent fibroblasts into proinflammatory cells that have the ability to promote tumor progression.
Reduced neonatal lung function and wheezing illnesses during the first 5 years of life
Authors: Anne C. van der Gugten, Cuno S.P.M. Uiterwaal, Nienke van Putte-Katier, Marije Koopman, Theo J.M. Verheij, Cornelis K. van der Ent
Journal: European Respiratory Journal (2012)

Studies of reduced neonatal lung function and wheezing illnesses during childhood show conflicting results. The aim of our study was to assess the association between resistance ( R rs ) and compliance ( C rs ) of the respiratory system by using the single occlusion technique (SOT) and prospectively collected wheezing illnesses during the first 5 years of life in a large birth cohort. SOT was performed during natural sleep before the age of 2 months. Information about wheezing illnesses was collected from the electronic patient file. 549 infants had a successful SOT measurement and complete medical records. Every kPa·L −1 ·s −1 increase in R rs was associated with 10% more consultations in the first 3 years of life. Every 10 mL·kPa −1 increase in C rs was associated with a 14% reduction in consultations in the first 3 years of life, 27% in the fourth to fifth years of life, and a lower probability of having asthma at the age of 5 years (OR 0.66). Children with late-onset or persistent wheezing had significant lower C rs values than their peers. An increased neonatal resistance is associated with more wheezing illnesses during infancy, while a reduced neonatal compliance is associated with more wheezing illnesses during the first 5 years of life, a late-onset or persistent wheezing phenotype, and asthma.
Single cell expression quantitative trait loci and complex traits
Authors: Enrico Petretto
Journal: Genome Medicine (2013)

The recently developed ability to quantify mRNA abundance and noise in single cells has allowed the effect of heritable variations on gene function to be re-evaluated. A recent study has shown that major sources of variation are masked when gene expression is averaged over many cells. Heritable variations that determine single-cell expression phenotypes may exert a regulatory function in specific cellular processes underlying disease. Masked effects on gene expression should therefore be modeled, not ignored.
Retroviral induction of acute lymphoproliferative disease and profound immunosuppression in adult C57BL/6 mice.
Authors: D E Mosier, R A Yetter, H C Morse
Journal: The Journal of Experimental Medicine (1985)

We have shown that a mixture of murine leukemia viruses (MuLV) causes the acute onset of lymphoproliferation and immunosuppression when injected into adult C57BL/6 mice. The ecotropic/MCF (mink cell focus-inducing) mixture of MuLV stimulates polyclonal B lymphocyte proliferation and differentiation to antibody-secreting cells. Serum Ig levels are elevated for all isotypes except IgA. The viral infection leads to a rapid decline in T lymphocyte responses to mitogens and alloantigens, as well as a decrease in helper cell activity. Specific antibody responses to both T-dependent and T-independent antigens are impaired, and the response of B lymphocytes to mitogens is abolished. The profound immunosuppression seems to be due to the MuLV-induced polyclonal activation of lymphocytes. No active suppression of normal lymphocyte responses by cells from virus-infected mice was observed. The disease induced by the LP-BM5 MuLV isolate thus seems a promising model for the study of lymphocyte activation and the mechanisms of retrovirus-induced immunosuppression.
Pachymeningitis in mixed connective tissue disease
Authors: K Ahmadi-Simab
Journal: Annals of the Rheumatic Diseases (2005)

hydrocephalus (fig 1).Because of the hydrocephalus, it was neurologically advisable not to perform a cerebrospinal fluid puncture.There was no indication of tuberculosis (chest x ray examination, tuberculin test, sputum culture) or any other infection.The neoplasia investigation was also negative.An anamnestic investigation showed that there was no need to use ibuprofen or sulindac.When the situation became life threatening we initiated immunosuppressive treatment with cyclophosphamide (100 mg/day), as well as intravenous steroids (100 mg) initially.The initial intravenous cortisone treatment relieved the headache symptoms.Follow up examinations for up to 1 year (every 3 months) showed remission of clinical and MRI findings with this treatment (fig 2).Stable partial remission occurred after 8 months, and oral administration of cyclophosphamide was stopped.Treatment to preserve remission was changed to azathioprine (100 mg).The prednisone dose was finally reduced to 5 mg.
Cell Phones, Cancer, and Children
Authors: J. D. Boice, R. E. Tarone
Journal: JNCI Journal of the National Cancer Institute (2011)

JNCI | Editorials 1211 We live in a high-tech world of electronics, constantly strolling through invisible fields of radio waves, television waves, microwaves, radar, and Wi-Fi networks. In the 1980s in the Nordic countries and in the 1990s in the United States, a new source of radio frequency waves came into widespread use: The cell phone, which emits nonionizing radio waves through an antenna commonly held close to the head. By 2009, the cell phone had become an integral part of everyday life, with more than 285 million subscribers to cell phone service in the United States (91% of the population) and more than 5 billion worldwide. This ubiquitous exposure to an emerging technology prompted the initiation of large-scale health studies (some started over 20 years ago) in the United States (1,2) and throughout the world (3,4). The results of these epidemiological investigations have been largely consistent and reassuring, with the World Health Organization (WHO) and the US National Cancer Institute concluding that there is no conclusive or consistent evidence that nonionizing radiation emitted by cell phones is associated with cancer risk (5,6). Amid this encouraging evidence from human observational studies, coupled with the negative findings from virtually all exper imental animal and in vitro studies and the absence of any known biological mechanism by which weak nonionizing radio waves emitted from cell phones could damage DNA and lead to cancer (7–9), it may therefore seem surprising that a monograph committee of the International Agency for Research on Cancer (IARC), an agency of the WHO, recently announced that cell phones may be “possibly carcinogenic to humans” (10). The change from “no conclusive evidence” to “possibly carcinogenic” was not new research (11), and it has understandably led to widespread public as well as media concern and confusion (12). The footnote accompanying the IARC press release (10) is often missed—that a “possibly carcinogenic to humans” (2B) classification by IARC is based on “limited evidence of carcinogenicity” and that “chance, bias, or confounding could not be ruled out with reasonable confidence” for the few positive associations reported in the literature. A published summary of the IARC Working Group conclusions (13) noted that some members found the epidemiologic evidence to be inadequate to support the 2B classification. Viewed in
HIV‐1‐specific RT inhibitors: Highly selective inhibitors of human immunodeficiency virus type 1 that are specifically targeted at the viral reverse transcriptase
Authors: Erik De Clercq
Journal: Medicinal Research Reviews (1993)

The TIBO, HEPT, nevirapine, pyridinone, BHAP, TSAO, and alpha-APA derivatives, although belonging to structurally diverging classes of molecules, share remarkable common features. They are specifically active against the reverse transcriptase of HIV-1 (TIBO and HEPT also, to a certain extent, against the reverse transcriptase of SIVagm strains), but not against the reverse transcriptases of HIV-2 or any other retroviruses. Nor are they active against any of the cellular DNA polymerases. These HIV-1-specific RT inhibitors seem to interact with a specific target site (YQYMDDLY) at positions 181-188, which is distinct from, but functionally and spatially related to, the substrate (dNTP) binding site. The tyrosine residues Y181 and Y188 play a crucial role in the interaction of TIBO and its congeners with their target site. The HIV-1-specific RT inhibitors have proven to inhibit the replication of various HIV-1 strains, including AZT-resistant HIV-1 strains, in different cell culture systems, including peripheral blood lymphocytes and monocyte/macrophages. In vitro they exhibit selectivity indexes of up to 5 orders of magnitude, which means that they are inhibitory to virus replication in cell culture at concentrations that are up to 100,000 times lower than the concentrations at which they are toxic to the host cells. As a rule, the HIV-1-specific RT inhibitors are orally bioavailable, as has been demonstrated with the TIBO and HEPT derivatives, nevirapine, pyridinones, and the alpha-APA derivatives in rats, dogs, monkeys, and humans. They sustain plasma drug levels that are well above the concentration required to inhibit virus replication in cell culture. Clinical studies have been undertaken with TIBO R82913, nevirapine, and pyridinones, and others (i.e., alpha-APA R89439) will soon follow. The problem of virus-drug resistance, which seems to readily emerge in vitro, will have to be addressed in the in vivo studies.