tbuckley/cabot-search huggingface dataset:
Abstract 3296: KLF9, a differentiation-associated transcription factor, suppresses Notch1 signaling and inhibits glioblastoma-initiating stem cells
Authors: Mingyao Ying, Yingying Sang, Yunqing Li, Hugo Guerrero-Cazares, Alfredo Quinones-Hinojosa, Angelo L. Vescovi, Charles G. Eberhart, Shuli Xia, John Laterra
Journal: Cancer Research (2011)

Abstract Tumor-initiating stem cells (alternatively called cancer stem cells, CSCs) are a subpopulation of tumor cells that plays unique roles in tumor propagation, therapeutic resistance and tumor recurrence. It is becoming increasingly important to understand the molecular signaling that regulates the self-renewal and differentiation of CSCs. Transcription factors are critical for the regulation of normal and neopolastic stem cells. The Krüppel-like family of transcription factors (KLFs) consists of 17 evolutionarily conserved zinc finger containing proteins with diverse regulatory functions. KLFs bind to GC-GT rich sites in gene promoter and enhancer regions and are known to contextually regulate the growth, proliferation, and differentiation of cells including non-neoplastic stem cells and cancer cells. Here, we examined the expression and function of KLF transcription factors in human glioblastoma (GBM)-drived neurosphere lines and low passage primary GBM-derived neurospheres that are enriched for tumor-initiating stem cells. We identify KLF9 as a relatively unique differentiation-induced transcription factor in GBM-derived neurospheres. KLF9 knockdown rescues GBM-derived neurospheres from Retinoic -acid-induced growth inhibition and differentiation. KLF9 induction is shown to induce neurosphere cell differentiation, inhibit neurosphere formation and deplete neurospheres of CD133+ stem-like cells. KLF9 induction also inhibits the growth of tumor xenografts established from GBM-derived neurospheres. We also show that KLF9 regulates GBM neurosphere cells by binding to the Notch1 promoter and suppressing Notch1 expression and downstream signaling. We compared the KLF9 expression between human GBM tumors and non-neoplastc human specimens. KLF9 is down regulated in human GBM tumors relative to normal brain. Our findings expand the role of KLF family members in stem cell and cancer biology, support KLF9 as a regulator of GBM malignancy, and as a potential biomarker and target for cancer therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3296. doi:10.1158/1538-7445.AM2011-3296
Clonal diversity of IL-4 and IL-13 expression in human allergen-specific T lymphocytes
Authors: David M. Essayan, Wan-Fang Han, Xiu-min Li, Hui-Qing Xiao, Jörg Kleine-Tebbe, Shau-Ku Huang
Journal: Journal of Allergy and Clinical Immunology (1996)

The expression of IL-4 and IL-13 was analyzed in a panel of short ragweed allergen (Amb a 1)–specific T-cell clones from an allergic subject and a nonallergic individual. The T cells from the allergic subject showed a predominantly T H0 phenotype. The T cells from the nonallergic individual produced undetectable levels of IL-4 and high levels of interferon-γ, suggesting a T H1 cytokine profile. However, all T-cell clones showed significantly higher levels of IL-13 secretion than IL-4 secretion, and no quantitative correlation could be found between the levels of IL-4 and IL-13 in the clones tested. Furthermore, both cytokines showed similar kinetics of expression in antigen-induced steady-state messenger RNA. Finally, both cytokines were induced by stimulation of the cells with either ionomycin alone or with a combination of ionomycin and phorbol myristate acetate. These results demonstrate that there is a significant clonal diversity and quantitative difference in the levels of IL-4 and IL-13 expression in allergen-specific human T cells. (J Allergy Clin Immunol 1996;98:1035-44.)
Human cystic fibrosis transmembrane conductance regulator directed to respiratory epithelial cells of transgenic mice
Authors: Jeffrey A. Whitsett, Chitta R. Dey, Barry R. Stripp, Kathryn A. Wikenheiser, Jean C. Clark, Susan E. Wert, Richard J. Gregory, Alan E. Smith, Jonathan A. Cohn, James M. Wilson, John Engelhardt
Journal: Nature Genetics (1992)
Hormone replacement therapy in chronic active hepatitis; a case report.
Authors: D Clements, J Rhodes
Journal: Gut (1993)

There is an increased incidence of osteoporosis in patients with chronic liver disease. Because patients with chronic active hepatitis (CAH) usually require corticosteroids for their liver disease prevention and treatment of bone loss presents a difficult problem. This case report describes a 41 year old female patient with CAH who had a high rate of bone loss. After an early menopause with noticeable menopausal symptoms, she was given transdermal oestrogen replacement therapy. The menopausal symptoms resolved completely, and there was no deterioration in her liver function tests or corticosteroid requirement. In addition, follow up quantitative bone mineral measurements over two years have shown improvement. This case shows the value of measurements of bone density, and oestrogen replacement therapy in CAH, even in the presence of continued corticosteroids.
Netherlands tops healthcare table that focuses on patients' perspective
Authors: R. Watson
Journal: BMJ (2008)

<h3>Background</h3> The Kalgoorlie gold miners’ cohort was established in 1994, consisting of all workers (males only) who attended workplace health surveys in 1961, 1962, 1974, and 1975. In this study the follow-up of the cohort has been extended to 2011. Our objectives were (i) to estimate cancer mortality and incidence, for both surface and underground miners; and (ii) to examine the hypothesis that (underground) mining may be protective against prostate cancer. <h3>Methods</h3> Standardised mortality and incidence ratios (SMRs and SIRs) and 95% confidence intervals (95% CI) were calculated to compare cancer mortality and incidence of the former Kalgoorlie miners with that of the Western Australian male population. Internal comparisons on duration of underground work were examined using Cox regression. <h3>Results</h3> During 52,440 person-years of follow-up, 1,922 deaths were observed. Increased mortality from any cause was observed for the miners (SMR = 1.34, 95% CI 1.28–1.40), with hazard ratios indicating a trend for duration working underground (p = 0.02). For any cancer, mortality was increased for the total group of miners (SMR = 1.25, 95% CI 1.14–1.37). In the Cox models, lung cancer mortality and incidence were particularly increased among underground miners, even after adjustment for smoking. The SMR for prostate cancer suggested a lower risk for underground miners, but this was not supported by the incidence data with a significantly increased incidence of prostate cancer (SIR = 1.26, 95% CI 1.03–1.54) among underground miners. <h3>Conclusions</h3> Overall cancer mortality and incidence was higher among Western Australian gold miners compared with the general population, especially for lung cancer and particularly for underground mining. This study does not support the hypothesis that miners have a decreased risk of prostate cancer: the results indicate a positive association between working as a miner and prostate cancer.
Fetal and maternal contributions to risk of pre-eclampsia: population based study
Authors: R. T. Lie, S. Rasmussen, H. Brunborg, H. K Gjessing, E. Lie-Nielsen, L. M Irgens
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To use familial patterns of recurrence of pre-eclampsia to investigate whether paternal genes expressed in the fetus contribute to the mother9s risk of pre-eclampsia and whether mother9s susceptibility to pre-eclampsia is related to maternal inheritance by mitochondrial DNA. <b>Design:</b> Linked data on pregnancies of different women who had children with the same father, and subsequently linked data on pregnancies of half sisters who either had same mother and different fathers or had same father and different mothers. <b>Setting:</b> Population based data from the Medical Birth Registry of Norway covering all births since 1967 (about 1.7 million) and the Norwegian Central Population Register. <b>Main outcome measures:</b> Relative risk of pre-eclampsia after a previous pre-eclamptic pregnancy in the family. Relative risks approximated by odds ratios. <b>Results:</b> If a woman becomes pregnant by a man who has already fathered a pre-eclamptic pregnancy in a different woman her risk of developing pre-eclampsia is 1.8 (95% confidence interval 1.2 to 2.6). If the woman has a half sister who had pre-eclampsia and with whom she shares the same mother but different fathers the risk of pre-eclampsia is 1.6 (0.9 to2.6). If the two sisters have the same father but different mothers the risk is 1.8 (1.01 to 2.9). <b>Conclusions:</b> Both the mother and the fetus contribute to the risk of pre-eclampsia, the contribution of the fetus being affected by paternal genes. Mitochondrial genes, which are transmitted by mothers, do not seem to contribute to the risk. <h3>Key messages</h3> Paternal genes in the fetus may contribute substantially to a pregnant woman9s risk of pre-eclampsia The role of the fetus may be as important as that of the mother Purely maternal inheritance (specifically by mitochondrial DNA) is probably not involved in pre-eclampsia Search for specific genes that predispose for pre-eclampsia should include the fetus as well as the mother
Infectious Hepatitis with Subacute Atrophy of the Liver
Authors: M. Jersild
Journal: New England Journal of Medicine (1947)

AN unusual and serious epidemic of infectious hepatitis has been present in Denmark since 1944. It differs from epidemics previously described in that the course has been extremely malignant and the disease, which is usually fatal, occurs almost exclusively in women after the menopause.In 1945 attention was called to this form of hepatitis in Denmark,1 and several other observers have had similar experiences.2 3 4 Since in most patients the disease progresses in a characteristic and uniform manner, the symptoms by which it has generally been manifested in our department are described below.As a rule the patient is an elderly . . .
Dyspnoea and worsening heart failure in patients with acute heart failure: results from the Pre‐RELAX‐AHF study
Authors: Marco Metra, John R. Teerlink, G. Michael Felker, Barry H. Greenberg, Gerasimos Filippatos, Piotr Ponikowski, Sam L. Teichman, Elaine Unemori, Adriaan A. Voors, Beth Davison Weatherley, Gad Cotter
Journal: European Journal of Heart Failure (2010)
Unbiased and Flexible Iterative Computer Program to Achieve Glucose Clamping
Authors: David R Matthews, John P Hosker
Journal: Diabetes Care (1989)

Glucose clamping has become a widely used test for assessing insulin sensitivity and β-cell function. We present a new method of achieving a reliable and unbiased clamp using an iterative computer program. After initial parameter estimation, the program uses no fixed algorithm or physiological preconceptions but makes predictions according to previous glycemic responses to infusion rates. The program can be used for human or animal studies and for euglycemic or hyperglycemic clamps. The program has flexible data entry, graphic display, running statistics of mean infusion data, and mean glucose levels and their standard deviations. These form part of the criteria for the assessment of glucose clamping, which includes the sampling interval, the duration of the clamp, the achieved glucose concentration (together with its coefficient of variation), and the percent change of glucose infused at the end of the clamp. Data for 151 consecutive clamp studies were analyzed. Median coefficient of variation of glucose values at the end of the clamp was 2%.
Abstract 505: Hypoxia inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis.
Authors: Pallavi Chaturvedi, Daniele Gilkes, Gregg Semenza
Journal: Cancer Research (2013)

Abstract Metastasis involves critical interactions between cancer and stromal cells. Intratumoral hypoxia promotes metastasis through activation of hypoxia-inducible factors (HIFs). We have demonstrated that HIFs mediate paracrine signaling between breast cancer cells (BCCs) and mesenchymal stem cells (MSCs) that facilitate metastasis. In an orthotopic implantation model, MSCs were recruited to primary breast tumors and promoted BCC metastasis to lymph nodes and lungs in a HIF-dependent manner. In vitro gene analysis of co-culture of MSCs with BCCs showed induced expression of the chemokine CXCL10 in MSCs and its cognate receptor CXCR3 in BCCs, which was augmented by hypoxia. Further we showed that CXCR3 expression was blocked in co-cultures treated with neutralizing antibody against CXCL10. Conversely, CXCL10 expression was blocked in MSCs co-cultured with BCCs that did not express CXCR3 or HIFs. MSC co-culture did not enhance the metastasis of CXCR3-deficient or HIF-deficient BCCs. Co-culture of MSCs with BCCs augmented HIF activity in BCCs. BCCs and MSCs expressed placental growth factor (PGF) and its cognate receptor VEGF1, respectively, in a HIF-dependent manner. The expression of CXCL10 by MSCs was dependent on PGF expression by BCCs. PGF promoted metastasis of BCCs and also facilitated homing of MSCs to tumors. Thus, HIFs mediate complex and bidirectional paracrine signaling between BCCs and MSCs that stimulates breast cancer metastasis. Citation Format: Pallavi Chaturvedi, Daniele Gilkes, Gregg Semenza. Hypoxia inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 505. doi:10.1158/1538-7445.AM2013-505
Heparin-binding ligands mediate autocrine epidermal growth factor receptor activation In skin organ culture.
Authors: S Stoll, W Garner, J Elder
Journal: Journal of Clinical Investigation (1997)

Exogenous EGF and TGF-alpha accelerate wound healing, but treatment effects are often modest. Using short-term human skin organ culture, we found that autocrine EGF receptor activation could account for this observation. Amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) transcripts were rapidly and markedly induced, whereas EGF and TGF-alpha mRNAs were undetectable or only slightly increased. Vascular permeability factor and keratin 6 transcripts were also strongly induced, albeit with a >/= 3 h delay relative to HB-EGF and amphiregulin. All four transcripts were upregulated in actual healing skin wounds, HB-EGF and keratin 6 being the most prominent. The highly EGF receptor-specific tyrosine kinase inhibitor PD153035 strongly inhibited induction of all four transcripts in organ culture, as well as release of immunoreactive HB-EGF into the medium. These effects were confirmed using the anti-EGF receptor mAb 225 IgG. Neither PD153035 nor 225 IgG was toxic to keratinocytes, as judged by calcein-AM uptake. PD153035 completely abrogated the proliferative phase of keratinocyte outgrowth in skin explant cultures, whereas it had no effect on the antecedent migratory phase. Based on these results, we conclude that EGF receptor activation by highly inducible, keratinocyte-derived heparin-binding ligands is an important mechanism for amplification and transmission of the cutaneous wound healing signal.
Osteoinduction with highly purified β-tricalcium phosphate in dog dorsal muscles and the proliferation of osteoclasts before heterotopic bone formation
Authors: N KONDO, A OGOSE, K TOKUNAGA, H UMEZU, K ARAI, N KUDO, M HOSHINO, H INOUE, H IRIE, K KURODA
Journal: Biomaterials (2006)
Tissue-specific histone modification and transcription factor binding in α globin gene expression
Authors: Marco De Gobbi, Eduardo Anguita, Jim Hughes, Jacqueline A. Sloane-Stanley, Jacqueline A. Sharpe, Christoph M. Koch, Ian Dunham, Richard J. Gibbons, William G. Wood, Douglas R. Higgs
Journal: Blood (2007)

To address the mechanism by which the human globin genes are activated during erythropoiesis, we have used a tiled microarray to analyze the pattern of transcription factor binding and associated histone modifications across the telomeric region of human chromosome 16 in primary erythroid and nonerythroid cells. This 220-kb region includes the α globin genes and 9 widely expressed genes flanking the α globin locus. This un-biased, comprehensive analysis of transcription factor binding and histone modifications (acetylation and methylation) described here not only identified all known cis-acting regulatory elements in the human α globin cluster but also demonstrated that there are no additional erythroid-specific regulatory elements in the 220-kb region tested. In addition, the pattern of histone modification distinguished promoter elements from potential enhancer elements across this region. Finally, comparison of the human and mouse orthologous regions in a unique mouse model, with both regions coexpressed in the same animal, showed significant differences that may explain how these 2 clusters are regulated differently in vivo.
CNS-directed AAV2-mediated gene therapy ameliorates functional deficits in a murine model of infantile neuronal ceroid lipofuscinosis
Authors: Megan A. Griffey, David Wozniak, Michael Wong, Ellen Bible, Kendra Johnson, Steven M. Rothman, Annie E. Wentz, Jonathan D. Cooper, Mark S. Sands
Journal: Molecular Therapy (2005)

The neuronal ceroid lipofuscinoses (Batten disease) are a group of inherited neurodegenerative diseases characterized by the progressive intralysosomal accumulation of autofluorescent material in many cells, visual defects, seizures, cognitive deficits, and premature death. Infantile neuronal ceroid lipofuscinosis (INCL) has the earliest onset (≈1.5 years of age) and is caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). Currently there is no effective treatment for children with INCL. In this study, newborn PPT1-deficient mice received two (cortex), four (cortex and hippocampus), or six (cortex, hippocampus, and cerebellum) bilateral intracranial injections of AAV2-PPT1. The AAV-treated animals had localized increases in PPT1 activity, decreased autofluorescent material, improved histologic parameters, and increased brain mass. In addition, the treated animals had dose-dependent improvements in a battery of behavioral tests and improved interictal electroencephalographic tracings. However, there was neither a significant decrease in seizure frequency nor an increase in longevity even in INCL animals receiving six injections. These data suggest that early treatment of INCL using gene transfer techniques can be efficacious. However, higher levels or a broader distribution of PPT1 expression, or both, will be required for more complete correction of this neurodegenerative disease.
Asymptomatic Mediastinal Mass in a 49-Year-Old Man
Authors: Muhammad A. Zaheer
Journal: JAMA (1979)

<h3>History</h3> An asymptomatic 49-year-old man was referred because of an abnormal chest roentgenogram. Findings from physical examination were normal. Chest roentgenograms, tomogram, and esophagogram are presented (Fig 1 through 4). <h3>Diagnosis</h3> Bronchogenic cyst. An oval hemogeneous shadow to the left of the upper posterior mediastinum was found on the chest roentgenogram. Fluoroscopy and barium study showed this mass to be paraesophageal.<sup>1</sup>It moved with swallowing. No intrinsic pulsations were seen. Differential diagnosis included enteric cyst, bronchogenic cyst, esophageal tumor (eg, leiomyoma), substernal thyroid, lymph node enlargement, and vascular lesion.<sup>2</sup> Radioactive iodine scan showed no uptake in the mass, and the thyroid gland appeared normal. Thoracic aortography was also normal. At surgery, a 5-cm diameter cyst was found loosely attached posteriorly to the esophageal wall. It contained mucoid material. Histological sections of the wall showed ciliated pseudostratified columnar epithelium and underlying hyaline cartilage. <h3>Comment</h3> Bronchogenic cysts are developmental in
COD LIVER OIL
Authors: Charles E. Bills
Journal: JAMA (1935)

<h3>To the Editor:—</h3> I have just read the editorials inThe Journal, March 16 and 23, entitled "Cod Liver Oil" (p. 926) and "Variations in Behavior of Vitamin D" (p. 1008). Each of these articles makes prominent reference to the recent publication from this laboratory, in which a physiologic difference between the vitamin D of cod liver oil and the vitamin D of bluefin tuna liver oil was demonstrated. Unfortunately, there is an error in each of these editorial interpretations, to which attention should be called. The first editorial states that "perhaps the most striking support for the peculiar efficacy of cod liver oil has been recently brought forward by Bills, Massengale and Imboden, who found that blue fin tuna liver oil with 40,000 units of vitamin D per gram was only one sixth as effective when assayed with chicks as was cod liver oil with only 100 units of
1008-15 Effectiveness of Heparin for Prevention of Coagulation Factor Activation During Radiofrequency Catheter Ablation
Authors: Satyendra Giri, Ellison Berns, Neal Lippman, Harlan R. Grogin, Patricia Stefanow, Selby Wajcs, Robert Bona
Journal: Journal of the American College of Cardiology (1995)
Inhibition of mast cell tryptase by inhaled APC 366 attenuates allergen-induced late-phase airway obstruction in asthma
Authors: Mamidipudi Thirumala Krishna, Anoop Chauhan, Louise Little, Karen Sampson, Richard Hawksworth, Tim Mant, Ratko Djukanovic, Tak Lee, Stephen Holgate
Journal: Journal of Allergy and Clinical Immunology (2001)
What Are We Teaching About Indigent Patients?
Authors: David L. Hartsuch
Journal: JAMA (1993)

To the Editor.  —In the article What Are We Teaching About Indigent Patients?,1Miles is highly critical of a private hospital's refusal to treat an indigent patient, and challenges the ethicality of referring such patients to county hospitals in lieu of accepting medical assistance as payment. Miles' assumption that this is an unethical practice is based on the ethic of egalitarianism. I believe that there are a variety of other valid ethics that Miles has ignored, and that teaching ethics based solely on egalitarianism may foster a system that sacrifices the quality of care for the majority and prevents physicians from achieving the greatest good.  The sad truth is that all organizations must recover their operating costs to continue performing their mission to the community. Regardless of the most noble intent, all benevolence must have a benefactor. Recognizing this fact, many hospitals have established charitable foundations to dispense resources
Decapsulation of Kidney for Chronic Bright's Disease.
Authors: James T. Jelks
Journal: JAMA (1902)

Hot Springs, Ark., March 4, 1902. <h3>To the Editor:</h3> —Since reading the admirable article of Dr. Geo. H. Edebohls, on decapsulation of the kidneys for chronic Bright's disease (<i>Medical Record</i>, Dec. 21, 1901, andThe Journal, Jan. 4, 1902, p. 62), I am impressed with its far-reaching possibilities. It opens up a vast field of work in the cure of otherwise hopeless cases. Why could not this same procedure be resorted to in cirrhosis of the liver before the stage of atrophy sets in? Decapsulation cf the upper surface of this organ would certainly take away a very great obstacle to the speedy formation of many large blood vessels for anastomotic duty. True, we have this anastomosis in a certain degree when we remove the epithelium by means of our friction with gauze sponges; but it is easy to see the vast difference between the small vessels which would penetrate