tbuckley/cabot-search huggingface dataset:
Activated fibronectin-secretory phenotype of mesenchymal stromal cells in pre-fibrotic myeloproliferative neoplasms
Authors: Rebekka K Schneider, Susanne Ziegler, Isabelle Leisten, Monica SV Ferreira, Anne Schumacher, Björn Rath, Dirk Fahrenkamp, Gerhard Müller-Newen, Martina Crysandt, Stefan Wilop, Edgar Jost, Steffen Koschmieder, Ruth Knüchel, Tim H Brümmendorf, Patrick Ziegler
Journal: Journal of Hematology & Oncology (2014)

We characterized bone marrow stromal cells (BMSC) from patients with pre-fibrotic myeloproliferative neoplasms (MPN). MPN-BMSC showed decreased capacity to stimulate the proliferation of colony-forming units of normal hematopoietic stem and progenitor cells and displayed increased matrix remodelling (in particular fibronectin deposition) compared to control BMSC. This finding was confirmed in pre-fibrotic MPN bone marrow biopsies in a tissue microarray (n = 34), which stained positive for fibronectin in the absence of reticulin as a standard myelofibrosis marker. Fibronectin expression correlated significantly with reduced haemoglobin levels in MPN-patients (p = 0.007; R2 = 0.42). Our data show significant cell-intrinsic alterations in MPN-MSC and suggest that Fibronectin expression might be applicable as a biomarker for the identification of early myelofibrotic transformation in reticulin-negative MPN.
Glucose Control Influences Glomerular Filtration Rate and Its Prediction in Diabetic Subjects
Authors: Vincent Rigalleau, Catherine Lasseur, Christelle Raffaitin, Caroline Perlemoine, Nicole Barthe, Philippe Chauveau, Christian Combe, Henri Gin
Journal: Diabetes Care (2006)

Hyperglycemia increases glomerular filtration rate (GFR), but the influence of HbA(1c) (A1C) on GFR and GFR's prediction by recommended equations remains to be determined.In 193 diabetic patients, we searched for an association between A1C and isotopically measured GFR (51Cr-EDTA) and their predictions by the Cockcroft and Gault formula (CG) and the modification of diet in renal disease (MDRD) equation. Their accuracy for the diagnosis of moderate (GFR <60 ml/min per 1.73 m(2)) or severe (GFR <30 ml/min per 1.73 m(2)) renal failure was compared from receiver operating characteristic (ROC) curves, before and after categorizing the patients as well (A1C <or=8%) or poorly controlled.The mean GFR was 57.0 +/- 34.8 ml/min per 1.73 m(2) and was well correlated with both estimations (CG r = 0.75, MDRD r = 0.83; P < 0.05). The areas under the ROC curves were higher with the MDRD (P < 0.05). A1C was correlated (P < 0.001) with the GFR (r = 0.29), MDRD (r = 0.38), CG (r = 0.26), and the absolute differences between the GFR and their CG but not MDRD estimations (r = 0.17, P < 0.05). Each +1% A1C was associated with +6.0 ml/min per 1.73 m(2) GFR (CG +5.6, MDRD +5.3). After separating well-controlled (n = 88, A1C 7.0 +/- 0.7%) and poorly controlled (n = 105, 9.6 +/- 1.3%) patients, the diagnostic accuracies were better (P < 0.05) for the MDRD, except for the diagnosis of moderate renal failure in well-controlled patients (NS).GFR and its estimations correlate with A1C. Although the relations between GFR and its estimations were not affected by the degree of glucose control, the precision and diagnostic accuracy of the CG formula were diminished for A1C >8%. The MDRD equation was more accurate and robust in diabetic patients with impaired renal function.
Dietary polyamines are essential luminal growth factors for small intestinal and colonic mucosal growth and development
Authors: Chr Löser, A Eisel, D Harms, U R Fölsch
Journal: Gut (1999)

Background Polyamines are essential for cell growth. Dietary and probably gut bacterial derived polyamines contribute significantly to the polyamine body pool. Aims To evaluate the influence of dietary, luminal polyamines on growth and development of different gastrointestinal organs in normally growing rats. Methods Male suckling Wistar rats were randomly allocated to four treatment groups: polyamine deficient diet (PDD); PDD plus antibiotics (neomycin 2 g/kg and metronidazole 34 mg/kg); PDD plus polyamine supplementation at normal concentrations; or normal standard laboratory chow. After a six month feeding period 7–10 animals/group were sacrificed. Results No differences in body weight gain, food consumption, or general behaviour could be observed between the four groups of animals. Feeding of PDD alone or PDD plus antibiotics resulted in a highly significant decrease in organ weight, protein content, and DNA content in small intestinal and colonic mucosa whereas no alterations were found in the liver. Conclusions Long term feeding of polyamine deficient diets resulted in a significant hypoplasia of small intestinal and colonic mucosa. Dietary, luminal polyamines are important local factors for growth and the development of small intestinal and colonic mucosa.
Violence against Women — A Challenge to the Supreme Court
Authors: Martha Minow
Journal: New England Journal of Medicine (1999)

This issue of the Journal includes two reports on risk factors for violent injuries to women. The findings of Kyriacou et al.1 and Grisso et al.,2 from case–control studies in hospital emergency rooms, are not surprising. But the public-policy implications deserve renewed attention as the Supreme Court considers whether to strike down the 1994 Violence against Women Act as unconstitutional.Kyriacou et al. report that the chief risk factors for injuries to women as a result of domestic violence are alcohol or drug abuse by male partners and having a partner who is unemployed or intermittently employed. Grisso et al. . . .
The Thymus Contains a High Frequency of Cells that Prevent Autoimmune Diabetes on Transfer into Prediabetic Recipients
Authors: Abdelhadi Saoudi, Benedict Seddon, Debbie Fowell, Don Mason
Journal: The Journal of Experimental Medicine (1996)

Rats of the PVG.RT1u strain develop autoimmune diabetes when thymectomized at 6 wk of age and are rendered relatively lymphopenic by a cumulative dose of 1,000 rads 137Cs γ-irradiation given in four split doses. Previous studies have shown that the disease is prevented by the intravenous injection of 5 × 106 CD4+ CD45RC− TCRαβ+ RT6+ peripheral T cells from normal syngeneic donors. These cells have a memory phenotype and are presumably primed to some extrathymic antigen. However, we now report that the CD4+ CD8− population of mature thymocytes is a very potent source of cells, with the capacity to prevent diabetes in our lymphopenic animals. As few as 6 × 105 of these cells protect ∼50% of recipients and the level of protection increases with cell dose. It appears that one characteristic of the intrathymic selection of the T cell repertoire is the generation of cells that regulate the autoimmune potential of peripheral T cells that have been neither clonally deleted intrathymically nor rendered irreversibly anergic in the periphery.
Acyclovir as treatment for aplastic anemia
Authors: A. Murat Tuncer
Journal: American Journal of Hematology (1989)

Acyclovir as Treatment for Aplastic AnemiaGomez-Almaguer et al. [l] have recently reported eight patients with idiopathic severe aplastic anemia who received acyclovir as the initial treatment.Causal factors are difficult to define in acquired aplastic anemia.When no related factors are reported, the cases are classified as ''idiopathic." Infections may cause aplastic anemia, too-.Infectious mononucleosis and viral hepatitis are the most important causes of severe form of aplastic anemia [2,3].Because there were insufficient details and documentation of the patients in this article, we could not explain the results.Acyclovir is a very safe antiviral agent, and it has no hematological side effects usually, but not always.We observed [4] a transient erytroblastopenia and leukopenia in 9-year-old female patient with severe herpes zoster who was treated with acyclovir (15 mg/kg/day) in three divided doses for 4 days, administered intravenously.The patient had no hematologic or oncologic disorders.In this first report of the acyclovir literature, transient erytroblastopenia and leukopenia began during the third day of therapy.On the fourth day of therapy, hemoglobin, red blood cell, hematocrit, and leukocyte were observed to be at their minimal levels: 9 g/dl, 3 million RBC/mm3, 28%, and 2,600 WBC /m3, respectively.A reduction of erythroid progenitors in the bone marrow also was seen.After discontinuation of therapy (after 5 days), hematologic values and bone marrow morphological parameters recovered without therapy.I conclude that when using acyclovir, especially in aplastic anemia, it is important to be careful.
Value of combined phenotypic markers in identifying inheritance of familial adenomatous polyposis.
Authors: F M Giardiello, G J Offerhaus, E I Traboulsi, J C Graybeal, I H Maumenee, A J Krush, L S Levin, S V Booker, S R Hamilton
Journal: Gut (1991)

Familial adenomatous polyposis is an autosomal dominant disease characterised by the development of hundreds of colorectal adenomas in young adults. Occult radio-opaque jaw lesions and pigmented ocular fundus lesions (formerly called congenital hypertrophy of the retinal pigment epithelium) are extraintestinal phenotypic markers for this disorder. We evaluated the usefulness of the combination of these markers for identifying patients who have inherited familial adenomatous polyposis. Forty three affected patients and 12 unaffected first degree relatives from 24 families with familial adenomatous polyposis, including four families without extraintestinal manifestations, were examined for both phenotypic markers. Thirty three of the 43 patients (77%) with familial adenomatous polyposis were positive for both markers, including patients from two families without extraintestinal manifestations. By contrast, only one of 12 (8%) unaffected first degree relatives over 35 years of age had both markers. The sensitivity of the combination of these markers in identifying patients who inherited familial adenomatous polyposis was 77%, the specificity 92%, the predictive value of a positive test 97%, the predictive value of a negative test 52%, and the efficacy 80%. The combined markers had improved efficacy over either marker alone (70% for occult radio-opaque jaw lesions and 67% for pigmented ocular fundus lesions). We conclude that the presence of both occult radio-opaque jaw lesions and pigmented ocular fundus lesions in a person at risk indicates a high probability of inheritance and expression of familial adenomatous polyposis.
Tyrosine Kinases as Targets for Cancer Therapy
Authors: Daniela S. Krause, Richard A. Van Etten
Journal: New England Journal of Medicine (2005)

Tyrosine kinases, enzymes that catalyze the transfer of phosphate from ATP to tyrosine residues in polypeptides, are ubiquitous, numerous, and of considerable clinical interest because they participate in the development of cancer and have become choice targets for therapeutic intervention. This comprehensive review discusses the molecular and clinical aspects of tyrosine kinases.
Coupling of Peripheral Tolerance to Endogenous Interleukin 10 Promotes Effective Modulation of Myelin-Activated T Cells and Ameliorates Experimental Allergic Encephalomyelitis
Authors: Kevin L. Legge, Booki Min, J. Jeremiah Bell, Jacque C. Caprio, Lequn Li, Randal K. Gregg, Habib Zaghouani
Journal: The Journal of Experimental Medicine (2000)

Several immune-based approaches are being considered for modulation of inflammatory T cells and amelioration of autoimmune diseases. The most recent strategies include simulation of peripheral self-tolerance by injection of adjuvant free antigen, local delivery of cytokines by genetically altered T cells, and interference with the function of costimulatory molecules. Although promising results have been obtained from these studies that define mechanisms of T cell modulation, efficacy, practicality, and toxicity, concerns remain unsolved, thereby justifying further investigations to define alternatives for effective downregulation of aggressive T cells. In prior studies, we demonstrated that an immunoglobulin (Ig) chimera carrying the encephalitogenic proteolipid protein (PLP)1 peptide corresponding to amino acid sequence 139–151 of PLP, Ig-PLP1, is presented to T cells ∼100-fold better than free PLP1. Here, we demonstrate that aggregation endows Ig-PLP1 with an additional feature, namely, induction of interleukin (IL)-10 production by macrophages and dendritic cells, both of which are antigen-presenting cells (APCs). These functions synergize in vivo and drive effective modulation of autoimmunity. Indeed, it is shown that animals with ongoing active experimental allergic encephalomyelitis dramatically reduce the severity of their paralysis when treated with adjuvant free aggregated Ig-PLP1. Moreover, IL-10 displays bystander antagonism on unrelated autoreactive T cells, allowing for reversal of disease involving multiple epitopes. Therefore, aggregated Ig-PLP1 likely brings together a peripheral T cell tolerance mechanism emanating from peptide presentation by APCs expressing suboptimal costimulatory molecules and IL-10 bystander suppression to drive a dual-modal T cell modulation system effective for reversal of autoimmunity involving several epitopes and diverse T cell specificities.
MTGR1 Is Required for Tumorigenesis in the Murine AOM/DSS Colitis-Associated Carcinoma Model
Authors: Caitlyn W. Barrett, Barbara Fingleton, Amanda Williams, Wei Ning, Melissa A. Fischer, Mary K. Washington, Rupesh Chaturvedi, Keith T. Wilson, Scott W. Hiebert, Christopher S. Williams
Journal: Cancer Research (2011)

Myeloid Translocation Gene, Related-1 (MTGR1) CBFA2T2 is a member of the Myeloid Translocation Gene (MTG) family of transcriptional corepressors. The remaining two family members, MTG8 (RUNX1T1) and MTG16 (CBFA2T3) are identified as targets of chromosomal translocations in acute myeloid leukemia (AML). Mtgr1(-/-) mice have defects in intestinal lineage allocation and wound healing. Moreover, these mice show signs of impaired intestinal stem cell function. Based on these phenotypes, we hypothesized that MTGR1 may influence tumorigenesis arising in an inflammatory background. We report that Mtgr1(-/-) mice were protected from tumorigenesis when injected with azoxymethane (AOM) and then subjected to repeated cycles of dextran sodium sulfate (DSS). Tumor cell proliferation was comparable, but Mtgr1(-/-) tumors had significantly higher apoptosis rates. These phenotypes were dependent on epithelial injury, the resultant inflammation, or a combination of both as there was no difference in aberrant crypt foci (ACF) or tumor burden when animals were treated with AOM as the sole agent. Gene expression analysis indicated that Mtgr1(-/-) tumors had significant upregulation of inflammatory networks, and immunohistochemistry (IHC) for immune cell subsets revealed a marked multilineage increase in infiltrates, consisting predominately of CD3(+) and natural killer T (NKT) cells as well as macrophages. Transplantation of wild type (WT) bone marrow into Mtgr1(-/-) mice, and the reciprocal transplant, did not alter the phenotype, ruling out an MTGR1 hematopoietic cell-autonomous mechanism. Our findings indicate that MTGR1 is required for efficient inflammatory carcinogenesis in this model, and implicate its dysfunction in colitis-associated carcinoma. This represents the first report functionally linking MTGR1 to intestinal tumorigenesis.
Gynaecology--medical or surgical?
Authors: S K Smith
Journal: BMJ (1996)

Historically, obstetrics and gynaecology brought together medically interested obstetricians and surgically interested gynaecologists,1 2 but gynaecology has always been seen as a surgical specialty. However, the increasing complexity of the subject and women's enhanced awareness of their reproductive health have opened up four subspecialties within obstetrics and gynaecology—reproductive medicine, maternofetal medicine, urogynaecology, and gynaecological oncology—all of which involve growing elements of medical expertise. So, should gynaecology remain a surgical specialty, or has it changed so much over the past 30 years that its training requirements need to be reviewed? And might a more medical approach to gynaecological disease lead to fewer women undergoing inappropriate surgical interventions?

One of the great achievements of obstetrics and gynaecology has been to establish a specialty in which women and not a disease or organ are the focus. There can be few …
Assessing Somatic Symptoms in Clinical Practice
Authors: Arthur J. Barsky
Journal: JAMA Internal Medicine (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Cervical Intraepithelial Neoplasia, Cervical Cancer, and HPV
Authors: Elizabeth A. Holly
Journal: Annual Review of Public Health (1996)

Major progress has been made to control cervical cancer in the United States and Europe using screening programs, although it remains a major cause of morbidity and mortality in the developing world. The association between cervical cancer and a sexually transmissible etiologic agent was hypothesized long before identification of human papillomaviruses (HPV) as agents that infected the genital tract. HPVs are among the most common sexually transmitted agents and have been shown to induce several squamous anogenital cancers, including squamous cell cancer of the cervix. After an etiologic role for HPV was identified in cervical cancer and CIN, efforts to understand the molecular biology of HPV were greatly expanded, enhanced by the advent of deoxyribonucleic acid (DNA) probes to identify HPV infection. Recent research has focused on specific types of HPV in relation to other recognized risk factors in the pathogenesis of CIN and invasive cervical cancer.
RhoJ Regulates Melanoma Chemoresistance by Suppressing Pathways That Sense DNA Damage
Authors: Hsiang Ho, Jayavani Aruri, Rubina Kapadia, Hootan Mehr, Michael A. White, Anand K. Ganesan
Journal: Cancer Research (2012)

Melanomas resist conventional chemotherapeutics, in part, through intrinsic disrespect of apoptotic checkpoint activation. In this study, using an unbiased genome-wide RNA interference screen, we identified RhoJ and its effector PAK1, as key modulators of melanoma cell sensitivity to DNA damage. We find that RhoJ activates PAK1 in response to drug-induced DNA damage, which then uncouples ATR from its downstream effectors, ultimately resulting in a blunted DNA damage response (DDR). In addition, ATR suppression leads to the decreased phosphorylation of ATF2 and consequent increased expression of the melanocyte survival gene Sox10 resulting in a higher DDR threshold required to engage melanoma cell death. In the setting of normal melanocyte behavior, this regulatory relationship may facilitate appropriate epidermal melanization in response to UV-induced DNA damage. However, pathologic pathway activation during oncogenic transformation produces a tumor that is intrinsically resistant to chemotherapy and has the propensity to accumulate additional mutations. These findings identify DNA damage agents and pharmacologic inhibitors of RhoJ/PAK1 as novel synergistic agents that can be used to treat melanomas that are resistant to conventional chemotherapies.
Spontaneous Tumor-Specific Humoral and Cellular Immune Responses to NY-ESO-1 in Hepatocellular Carcinoma
Authors: Firouzeh Korangy, Lars A. Ormandy, Jörg S. Bleck, Jürgen Klempnauer, Ludwig Wilkens, Michael P. Manns, Tim F. Greten
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Hepatocellular carcinoma (HCC) is the fifth most common cancer around the world. Although several therapeutic approaches for treatment of HCC are available, survival rates for HCC patients are still very poor because of inefficient treatment options. For HCC, as well as other tumors, antigen-specific immunotherapy remains a viable approach that is dependent on the definition of tumor-associated antigens. NY-ESO-1, a member of the cancer testis antigen family, is one possible candidate for a tumor-specific antigen in HCC. The aim of this study was to show the relevance of NY-ESO-1 in hepatocellular carcinoma. Experimental Design: Sera samples from 189 HCC patients were analyzed for NY-ESO-1-specific antibodies. Forty-nine HCC patients were screened for NY-ESO-1 mRNA expression in HCC tissue. Selected patients were followed for up to 3 years to correlate their immune response with their clinical course of events. NY-ESO-1-specific CD4+ and CD8+ T-cell responses from NY-ESO-1 seropositive patients were analyzed and a NY-ESO-1+ specific cytotoxic T-cell line was generated. Results: Twelve of 49 analyzed tumor samples expressed NY-ESO-1 mRNA and 23 of 189 patients showed NY-ESO-1-specific antibody responses. These humoral immune responses were accompanied by NY-ESO-1-specific functional CD4+ and CD8+ T-cell responses. Finally, NY-ESO-1 humoral responses were dependent on the presence of NY-ESO-1-expressing tumors. Conclusions: This is the first report of a spontaneous immune response in HCC patients to a known tumor-specific antigen, NY-ESO-1 protein. Our data favor the possibility of immunotherapeutic strategies for the treatment of HCC.
The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin
Authors: M.S. Kim, C.J. Small, S.A Stanley, D.G.A. Morgan, L.J. Seal, W.M. Kong, C.M.B. Edwards, S. Abusnana, D. Sunter, M.A. Ghatei, S.R. Bloom
Journal: Journal of Clinical Investigation (2000)

Prolonged fasting is associated with a downregulation of the hypothalamo-pituitary thyroid (H-P-T) axis, which is reversed by administration of leptin. The hypothalamic melanocortin system regulates energy balance and mediates a number of central effects of leptin. In this study, we show that hypothalamic melanocortins can stimulate the thyroid axis and that their antagonist, agouti-related peptide (Agrp), can inhibit it. Intracerebroventricular (ICV) administration of Agrp (83-132) decreased plasma thyroid stimulating hormone (TSH) in fed male rats. Intraparaventricular nuclear administration of Agrp (83-132) produced a long-lasting suppression of plasma TSH, and plasma T4. ICV administration of a stable α-MSH analogue increased plasma TSH in 24-hour–fasted rats. In vitro, α-MSH increased thyrotropin releasing hormone (TRH) release from hypothalamic explants. Agrp (83-132) alone caused no change in TRH release but antagonized the effect of α-MSH on TRH release. Leptin increased TRH release from hypothalami harvested from 48-hour–fasted rats. Agrp (83-132) blocked this effect. These data suggest a role for the hypothalamic melanocortin system in the fasting-induced suppression of the H-P-T axis.