tbuckley/cabot-search huggingface dataset:
Evidence that SOM230 can prevent experimental mammary hyperplasia by blocking IGF-I and thus estrogen action in the mammary gland: preliminary evidence for an effect in humans.
Authors: W Ruan, B Singh, J Smith, D Axelrod, DL Kleinberg
Journal: Cancer Research (2009)

Abstract Abstract #5084 Background: Antiestrogens or aromatase inhibitors are used for breast cancer chemoprevention, however, they are poorly tolerated. We have shown that IGF-I is required to permit estrogen and progesterone action in the mammary gland. A novel somatostatin analog, SOM230, which binds to several somatostatin subtype receptors (SSTR), prevents estrogen action by reducing pituitary growth hormone, and also by a direct IGF-I action inhibitory effect on the mammary gland. Menopausal symptoms have not been observed in acromegalic patients receiving SOM230. Material and Methods: Several approaches have been undertaken. 1) We developed a model of hyperplasia in hypophysectomized and oophorectomized female rats. Hyperplasia was induced by treatment with 600 mcg hGH and follicular phase concentrations of estradiol. 2) To assess translatability to humans we cell proliferation (Ki67) and apoptosis (TUNEL) were measured in normal human breast from reduction mammoplasty and in samples of proliferative fibrocystic change (FCC). 3) We also measured expression of SSTR in atypical ductal hyperplasia and DCIS, and 4) A proof of principal trial with SOM230 has begun accrual to determine whether SOM230 acts in human breast as in rats. Results: 1) hGH and E2 caused florid hyperplasia in rat mammary glands within a week. Twenty-six percent of gland structures exhibited hyperplasia with 50% of those showing florid hyperplasia. SOM230 reduced the number of areas of florid hyperplasia to 7.5 ±0.5 from 18.9±1.3 (p&amp;lt;0.001). This was accomplished by a reduction in cell proliferation and an increase in apoptosis. Interestingly, co-administration with tamoxifen provided no additional benefit over that of SOM230. 2) Proliferative lesions from human breast had 8.09 % of cells stain for Ki67. 3) All 5 somatostatin subtype receptor (SSTR) were present in pathology samples of atypical hyperplasias and DCIS, but SSTR3 and 5 were present in highest concentrations. SSTR 3 is the receptor most likely to mediate the effect of SOM230 with SSTR5 being the next most likely. 4) In the first patient tested we found that SOM230 increased apoptosis and reduced cell proliferation (1000 cells counted).&amp;#x2028; &amp;#x2028; Discussion: Our data show that SSTR are present in ADH and DCIS and normal breast tissue. Our data also show that SOM230 can prevent cell proliferation and increase apoptosis both in rats and humans. Thus, further clinical trials will be important as SOM230 may have a role in breast cancer chemoprevention. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5084.
Novel compound heterozygous mutations in the fructose-1,6-bisphosphatase gene cause hypoglycemia and lactic acidosis
Authors: Sungdae Moon, Ju-Hee Kim, Je-Ho Han, Seung-Hyun Ko, Yu-Bae Ahn, Ju-Hoon Kim, Song-Hyun Yang, Ki-Ho Song
Journal: Metabolism (2010)
Abstract 1535: Intratumoral chitosan/interleukin-12 immunotherapy reduces breast cancer metastasis
Authors: Jimmy Nhu Vo
Journal: Cancer Research (2012)

Abstract Interleukin-12 (IL-12) is a potent antitumor cytokine that exhibits significant clinical toxicities after systemic administration. Local delivery of IL-12 has been shown to significantly reduce this threat. Our lab has recently shown that local delivery of IL-12 with the biopolymer chitosan can eliminate aggressive murine tumors while minimizing the chances for toxicity. In addition to eliminating the tumors, our lab has demonstrated that local chitosan/IL-12 immunotherapy can lead to the activation and expansion of CD8+ T cells and natural killer cells, increased production of interferon-gamma, and activation of dendritic cells that can recognize and attack these tumor cells. This immune response was evaluated for efficacy in preventing tumor metastasis. Mice bearing 4T1 tumors were treated with DPBS, IL-12, chitosan, or chitosan-IL-12 prior to surgical resection of the primary tumor. Survival analysis returned survival rates of 0%, 25%, 0%, and 40% respectively. In a separate study, lungs were examined for metastatic nodules revealing that mice treated with chitosan/IL-12 displayed significantly fewer nodules than other treatment groups. Based on the data obtained thus far, chitosan/IL-12 shows promising potential as an immunotherapy to reduce metastatic disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1535. doi:1538-7445.AM2012-1535
Role of IL12 in genetic immunization against WHV-core antigen: induction of TH1 immune responses and protection against woodchuck hepatitis virus (WHV)
Authors: R. Garcia, B.Blanco Urgoiti, P. Berraondo, A. Vales, R.Sanchez de la Rosa, J.J. Lasarte, S. Hervas-Stubbs, F. Borras, J. Ruiz, J. Prieto
Journal: Journal of Hepatology (2001)
Radiation Dosage Estimation and Health Risk
Authors: Fred C. Maienschein
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Erroneous conclusions will be drawn from the article of Wing et al,<sup>1</sup>which described evidence of radiation effects in Oak Ridge (Tenn) National Laboratory workers, if the very large biases and uncertainties in relating effects to radiation doses are not recognized. The problem arises because the radiation-dose records represent no more than lower limits, and the derived radiation effects per sievert are thus upper limits. Why are the radiation-dose records so uncertain and so biased? From the Figure in the Wing et al article, it is clear that most of the relevant radiation dose was recorded before about 1960. In this period, the purpose of the radiationdose monitoring program was to detect large exposures. It was not intended to detect and measure low-dose levels of the magnitude reported by Wing et al, which scarcely exceeded natural background, on the average. In particular, radiation-dose readings less than
Dual-reactive B cells are autoreactive and highly enriched in the plasmablast and memory B cell subsets of autoimmune mice
Authors: Emilie M. Fournier, Maria-Gabriela Velez, Katelyn Leahy, Cristina L. Swanson, Anatoly V. Rubtsov, Raul M. Torres, Roberta Pelanda
Journal: The Journal of Experimental Medicine (2012)

Rare dual-reactive B cells expressing two types of Ig light or heavy chains have been shown to participate in immune responses and differentiate into IgG(+) cells in healthy mice. These cells are generated more often in autoreactive mice, leading us to hypothesize they might be relevant in autoimmunity. Using mice bearing Igk allotypic markers and a wild-type Ig repertoire, we demonstrate that the generation of dual-κ B cells increases with age and disease progression in autoimmune-prone MRL and MRL/lpr mice. These dual-reactive cells express markers of activation and are more frequently autoreactive than single-reactive B cells. Moreover, dual-κ B cells represent up to half of plasmablasts and memory B cells in autoimmune mice, whereas they remain infrequent in healthy mice. Differentiation of dual-κ B cells into plasmablasts is driven by MRL genes, whereas the maintenance of IgG(+) cells is partly dependent on Fas inactivation. Furthermore, dual-κ B cells that differentiate into plasmablasts retain the capacity to secrete autoantibodies. Overall, our study indicates that dual-reactive B cells significantly contribute to the plasmablast and memory B cell populations of autoimmune-prone mice suggesting a role in autoimmunity.
Establishing Health Care Performance Standards in an Era of Consumerism
Authors: Kenneth W. Kizer
Journal: JAMA (2001)

As the US health care system begins to reengineer itself to address the need for quality improvement, it also is being actively reshaped by the expectations of consumers. The confluence of these forces requires a new approach to setting health care performance standards. The National Quality Forum (NQF) has been established as a private, not-for-profit, open membership, public benefit corporation for the purposes of developing consensus about standardized health care performance measures, reporting mechanisms, and a national strategy for health care quality improvement. The NQF has broad representation from all segments of the health care industry and provides an equitable way of addressing the disparate priorities of health care's many stakeholders. Agreement and implementation of standardized health care performance measures and achievement of quality improvement in the emerging era of consumerism will be facilitated by (1) establishing national goals for health care quality; (2) embracing public policy that recognizes the complementary roles of quality improvement, cost control, and improved access; (3) giving greater priority to measuring and reporting the performance of those aspects of the health care system that directly affect consumers; (4) focusing on creating a health care culture of excellence; and (5) promoting the active collaboration of all stakeholders.
Peripheral blood mononuclear cell production of IFN-γ at one year of age is decreased in children with atopic dermatitis
Authors: William A Neaville, Kelly S Anklam, Kathy A Roberg, Kiva J Adler, Stephanie H Gilbertson-White, Kirstin T Carlson-Dakes, Douglas F Dasilva, Sarah A Ellerman-Sund, Rebekah J Hamilton, Ronald Gargnon
Journal: Journal of Allergy and Clinical Immunology (2002)
ELEVATED CYSTATIN C IS A SIGNIFICANT INDEPENDENT PREDICTOR OF MORTALITY AND CONTRAST INDUCED NEPHROPATHY IN PATIENTS WITH PERIPHERAL ARTERY DISEASE
Authors: Gwang Sil Kim, Young-Guk Ko, Dong-Ho Shin, Byeong-Keuk Kim, Jung-Sun Kim, Donghoon Choi, Myeong-Ki Hong, Yang Soo Jang
Journal: Journal of the American College of Cardiology (2014)
Biochemical Frontiers in Medicine.
Authors: Kurt Stern
Journal: JAMA (1963)

To bridge the gap between a medical education completed 10 or more years ago and the present "information explosion," is a problem not susceptible to any single, simple solution. One of the better palliative measures, the "arm-chair" postgraduate course, is represented by this book. Its essential theme is the concept of "molecular" disease, which not only has become indispensable for theory, but has also penetrated into the daily practice of medicine. From the vast storehouse of recent biochemical knowledge, the editor and four additional contributors have selected some significant topics on which newer information should be more widely disseminated. In an illuminating chapter on the biochemical basis of the newer diagnostic methods in clinical medicine O. Bodansky discusses catecholamines in relation to pheochromocytoma; the significance of 5-hydroxytryptamine in malignant carcinoid; problems of bilirubin determination and metabolism; and porphyrias and porphyrin metabolism. In another excellent contribution E. Farber deals with selected
Prostatectomy by the Vesico-capsular Method
Authors: R. E. B. Tagart
Journal: BMJ (1961)

MEDICLH J 21ALendocrine balance.Loeser's (1959) suggestion, that the good results of Watson and Turner (1959) were primarily due to the large doses of testosterone used, could go a long way towards explaining the poor results in the present series.Another reason for failure might be the relatively small doses of thiotepa used, though larger doses probably would have been hazardous.Hall et al. (1960) emphasized that cytotoxic agents should be tested not only in differing doses but by different routes of administration.It is probable that the future of chemotherapy in malignant disease lies with drugs with a greater cytotoxic action on tumour cells and bone-marrow cells (a higher " therapeutic index ") than thiotepa; with regional transfusion (Abel, 1960); or with measures deliberately designed to produce severe bone-marrow depression followed by bone-marrow (Brit.med.J., 1960) or foetal cell (Kay and Constandoulakis, 1959) infusions.Bridges et al. (1960) report the case of a patient with disseminated breast carcinoma who received 225 mg. of thiotepa intramuscularly over 18 days.Severe pancytopenia ensued, but the patient recovered after infusion of foetal liver cells.A remarkable improvement in the patient's condition was reported, with a remission at that time lasting to five months.One more factor deserves comment.The one benefit obtained in all patients by the use of thiotepa has been that on morale.Both the patients and their relatives feel that something is being done, and hope is retained.Summary Thiotepa has been used as a palliative measure in 12 patients with advanced carcinoma of the breast, who were deteriorating in spite of bilateral adrenalectomy and oophorectomy.In only two patients has a palliative effect been seen.The possible reasons for the failure of thiotepa in these patients are discussed.I thank Mr. Donald Barlow for permission to study his patients, and Dr. Thomas Parkinson for much help
8-Epi-PGF2alpha induces airflow obstruction and airway plasma exudation in vivo.
Authors: A Okazawa, I Kawikova, Z H Cui, B E Skoogh, J Lötvall
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

8-Epi-prostaglandin F2alpha (8-epi-PGF2alpha) is an F2-isoprostane formed mainly via noncyclooxygenase pathways in vivo. We investigated whether 8-epi-PGF2alpha has any effect on airflow obstruction and plasma exudation in vivo. Airflow obstruction was quantified by measuring lung resistance (RL) in anesthetized and ventilated guinea pigs, and plasma exudation was quantified by the Evans Blue dye method (20 mg/kg intravenously). Intratracheal instillation of 8-epi-PGF2alpha (1 nmol or 10 nmol) caused dose-related increases in RL. Furthermore, the higher dose of 8-epi-PGF2alpha produced Evans Blue dye extravasation in main bronchi and intrapulmonary airways. A prostanoid TP-receptor antagonist, BAY u3405 (1 mg/kg intravenously), abolished the airway effects of 8-epi-PGF2alpha (10 nmol). A thromboxane A2 (TxA2) synthase inhibitor, OKY-406 (30 mg/kg intravenously), significantly attenuated these effects of 8-epi-PGF2alpha (10 nmol). The level of TxB2, a stable TxA2 metabolite, increased in bronchoalveolar lavage fluid (BALF) after 8-epi-PGF2alpha instillation. We conclude that 8-epi-PGF2alpha causes airflow obstruction and plasma exudation in vivo. This effect may be mediated primarily via prostanoid TP-receptors, and a secondary generation of TxA2 may be involved in part of the airway responses in 8-epi-PGF2alpha in the guinea pig.
Discoidin domain receptor 1 regulates bronchial epithelial repair and matrix metalloproteinase production
Authors: M.E. Roberts, L. Magowan, I.P. Hall, S.R. Johnson
Journal: European Respiratory Journal (2010)

Discoidin domain receptor (DDR)1 is an extracellular matrix (ECM)-sensing receptor tyrosine kinase, which is activated by collagen and expressed in bronchial epithelium. DDR1 is responsible for maintaining the normal structure of skin and kidney epithelia and we hypothesised that DDR1 plays a regulatory role in bronchial epithelial integrity by transducing signals from the airway ECM. Effects of DDR1 depletion were studied using RNA interference in primary human bronchial epithelial cells (HBECs) and BEAS-2B cells. The effects of overexpression of DDR1a and DDR1b in BEAS-2B cells were studied using a plasmid vector. We measured the effects on epithelial repair using a scratch wounding model, and levels of matrix metalloproteinases (MMPs) by gelatin zymography (MMP-2 and -9) and ELISA (MMP-7). We showed that knockdown of DDR1 slowed epithelial repair by 50%, which was associated with a reduction in levels of MMP-7, whilst DDR1 overexpression enhanced epithelial repair. DDR1 knockdown reduced proliferation of HBECs, but had no significant effect on adhesion to collagen I or other matrix substrates. These data suggest that ECM signalling via DDR1 regulates aspects of bronchial epithelial repair, integrity and MMP expression in the airways.
Retinoids ameliorate insulin resistance in a leptin-dependent manner in mice
Authors: Hiroyuki Tsuchiya, Yoshito Ikeda, Yu Ebata, Chihiro Kojima, Rikutaro Katsuma, Tatsuaki Tsuruyama, Tomohiko Sakabe, Kohei Shomori, Noriko Komeda, Shoko Oshiro, Hideharu Okamoto, Kazuko Takubo, Susumu Hama, Koichi Shudo, Kentaro Kogure, Goshi Shiota
Journal: Hepatology (2012)

Transgenic mice expressing dominant-negative retinoic acid receptor (RAR) α specifically in the liver exhibit steatohepatitis, which leads to the development of liver tumors. Although the cause of steatohepatitis in these mice is unknown, diminished hepatic expression of insulin-like growth factor-1 suggests that insulin resistance may be involved. In the present study, we examined the effects of retinoids on insulin resistance in mice to gain further insight into the mechanisms responsible for this condition. Dietary administration of all - trans -retinoic acid (ATRA) significantly improved insulin sensitivity in C57BL/6J mice, which served as a model for high-fat, high-fructose diet–induced nonalcoholic fatty liver disease (NAFLD). The same effect was observed in genetically insulin-resistant KK - A y mice, occurring in concert with activation of leptin-signaling pathway proteins, including signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2. However, such an effect was not observed in leptin-deficient ob/ob mice. ATRA treatment significantly up-regulated leptin receptor (LEPR) expression in the livers of NAFLD mice. In agreement with these observations, in vitro experiments showed that in the presence of leptin, ATRA directly induced LEPR gene expression through RARα, resulting in enhancement of STAT3 and insulin-induced insulin receptor substrate 1 phosphorylation. A selective RARα/β agonist, Am80, also enhanced hepatic LEPR expression and STAT3 phosphorylation and ameliorated insulin resistance in KK - A y mice. Conclusion: We discovered an unrecognized mechanism of retinoid action for the activation of hepatic leptin signaling, which resulted in enhanced insulin sensitivity in two mouse models of insulin resistance. Our data suggest that retinoids might have potential for treating NAFLD associated with insulin resistance. (Hepatology 2012)
Causes of Insertion Sequences Abundance in Prokaryotic Genomes
Authors: Marie Touchon, Eduardo P. C. Rocha
Journal: Molecular Biology and Evolution (2007)

Insertion sequences (ISs) are the smallest and most frequent transposable elements in prokaryotes where they play an important evolutionary role by promoting gene inactivation and genome plasticity. Their genomic abundance varies by several orders of magnitude for reasons largely unknown and widely speculated. The current availability of hundreds of genomes renders testable many of these hypotheses, notably that IS abundance correlates positively with the frequency of horizontal gene transfer (HGT), genome size, pathogenicity, nonobligatory ecological associations, and human association. We thus reannotated ISs in 262 prokaryotic genomes and tested these hypotheses showing that when using appropriate controls, there is no empirical basis for IS family specificity, pathogenicity, or human association to influence IS abundance or density. HGT seems necessary for the presence of ISs, but cannot alone explain the absence of ISs in more than 20% of the organisms, some of which showing high rates of HGT. Gene transfer is also not a significant determinant of the abundance of IS elements in genomes, suggesting that IS abundance is controlled at the level of transposition and ensuing natural selection and not at the level of infection. Prokaryotes engaging in obligatory associations have fewer ISs when controlled for genome size, but this may be caused by some being sexually isolated. Surprisingly, genome size is the only significant predictor of IS numbers and density. Alone, it explains over 40% of the variance of IS abundance. Because we find that genome size and IS abundance correlate negatively with minimal doubling times, we conclude that selection for rapid replication cannot account for the few ISs found in small genomes. Instead, we show evidence that IS numbers are controlled by the frequency of highly deleterious insertion targets. Indeed, IS abundance increases quickly with genome size, which is the exact inverse trend found for the density of genes under strong selection such as essential genes. Hence, for ISs, the bigger the genome the better.
THE REMOVAL OF SUPERFLUOUS HAIR
Authors: Herman Goodman
Journal: JAMA (1925)

<h3>To the Editor:</h3> —The advertising pages of the less particular urban daily papers run notices appealing to the vanity of persons with excessive hair in undesirable locations and promising relief without danger by the use of supposedly modified or improved roentgen rays not available to the general practitioner. Our offices, clinics and dermatologic meetings are receiving increasing numbers of persons who have been misguided enough to have superfluous hairs removed by this means. Their faces now disclose objective signs of overdosage not so acceptable to the patient as the loss of hair. It seems hardly necessary to state that, early in the experimental application of the roentgen ray, its ultimate dangers were quite unknown. Now that years have passed, new martyrs of advancing science are laid to rest following devastation of tissue repeatedly exposed to the bombardment of the rays. The dangerous sequelae of roentgen-ray exposure are guarded against by
Intravenous Iron Alone Is Equally Effective With the Combination of Iron and Erythropoietin for the Treatment of Iron-Deficiency Anemia in Advanced Heart Failure
Authors: John V. Terrovitis, Elisabeth Kaldara, Argyrios Ntalianis, Stefania Sventzouri, Chris Kapelios, Despina Barbarousi, Charis Matsouka, John N. Nanas
Journal: Journal of the American College of Cardiology (2012)