tbuckley/cabot-search huggingface dataset:
Abstract 3485: Inhibition of Notch signaling enhances the antitumor efficacy of chemotherapy in triple negative breast cancer through reduction of cancer stem cells
Authors: Ping Wei, Ming Qiu, Ivy Jiang, Christopher Carroll, Guangzhou Han, Isha Rymer, Eugenia Kraynov, Aidong Wu, Stephane Thibault, Donna Stone, Yijie Gao, Susan Sofia, Jorge Gallo, Janet White, Gary Li, Jennifer Yang, Gerrit Los
Journal: Cancer Research (2012)

Abstract Triple negative breast cancer (TNBC) is characterized by lack of estrogen receptor (ER), progesterone receptor (PR) or Her2/neu. It is known to be particularly aggressive and refractory to current chemotherapies. Tumor-initiating cells (TICs) have been postulated as responsible for treatment failure for this type of cancer. Recent evidence suggests that Notch signaling may play a role in regulation of TIC self-renewal and differentiation hence present a promising target for development of novel therapies for TNBC. We previously discovered a mouse monoclonal Ab (mu-hN1) that produces robust efficacy in both T-cell acute lymphoblastic leukemia and TNBC by specifically blocking human Notch1 signaling in tumor cells. We subsequently produced a humanized Notch1 mAb (hu-hN1) that retained similar characteristics and activities compared to the mouse prototype mu-hN1. To gain insights into the mechanisms of Notch1 blockade on TNBC tumor grow inhibition (TGI), we evaluated the effect of hu-hN1 on apoptosis, proliferation and TIC self-renewal in Notch-driven Sum149 and a patient derived xenograft (PDX) TNBC models. We showed that hu-hN1 inhibited Notch signaling by reduction of NICD (Notch intracellular domain) and target genes Hes-1 and cMyc in Sum149 tumors. Inhibition of Notch signaling led to significant TGI either as a single agent or in combination with Docetaxel. TGI of hu-hN1 appeared to be in part due to induction of apoptosis in the tumor cells. More interestingly, treatment with this Ab caused reduction in mammosphere formation and CD44+/CD133+/ESA+ cell population. It also resulted in decrease in tumor incidence and delay in tumor recurrence, suggesting an anti-TIC activity of the agent. Further investigation in a PDX TNBC model confirmed the robust tumor efficacy and anti-TIC effect of hu-hN1. Taken together, our findings suggest that anti-Notch1 mAbs may provide novel therapies to improve the efficacy of conventional treatments by directly targeting the TIC niche. They may also delay tumor recurrence and hence have a major impact on cancer patient survival. 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 3485. doi:1538-7445.AM2012-3485
Bone Scan of Advanced Polycythemia Vera With Malignant Transformation
Authors: PINA C. SEYMOUR, BRUCE R. LINE
Journal: Clinical Nuclear Medicine (1996)

A 69-year-old man with polycythemia vera and myelofibrosis was seen with a 2-week history of increasing arm pain. A bone scan showed diffuse prominence of the long bones, especially in the metaphyseal and epiphyseal regions of the lower extremities. There was relative prominence of the proximal right humerus that suggested the presence of a malignant process in addition to marrow space expansion secondary to myelofibrosis. An MRI of the right upper extremity showed a permeated lesion in the proximal right humerus extending into the adjacent soft tissue with a large soft tissue component. At surgery, a biopsy was followed by placement of a humeral rod. The morphologic features of the tumor together with CD34 positivity were consistent with a granulocytic sarcoma. This is the first reported case of bone scintigraphic findings in advanced p. vera with myelofibrosis and malignant transformation. The case illustrates the scintigraphic appearance of extensive expansion of the marrow and suggests the importance of vigilance for relatively subtle changes of complicating malignancies.
Environmental endocrine disruption: an effects assessment and analysis.
Authors: T M Crisp, E D Clegg, R L Cooper, W P Wood, D G Anderson, K P Baetcke, J L Hoffmann, M S Morrow, D J Rodier, J E Schaeffer, L W Touart, M G Zeeman, Y M Patel
Journal: Environmental Health Perspectives (1998)

This report is an overview of the current state of the science relative to environmental endocrine disruption in humans, laboratory testing, and wildlife species. Background information is presented on the field of endocrinology, the nature of hormones, and potential sites for endocrine disruption, with specific examples of chemicals affecting these sites. An attempt is made to present objectively the issue of endocrine disruption, consider working hypotheses, offer opposing viewpoints, analyze the available information, and provide a reasonable assessment of the problem. Emphasis is placed on disruption of central nervous system--pituitary integration of hormonal and sexual behavioral activity, female and male reproductive system development and function, and thyroid function. In addition, the potential role of environmental endocrine disruption in the induction of breast, testicular, and prostate cancers, as well as endometriosis, is evaluated. The interrelationship of the endocrine and immune system is documented. With respect to endocrine-related ecological effects, specific case examples from the peer-reviewed literature of marine invertebrates and representatives of the five classes of vertebrates are presented and discussed. The report identifies some data gaps in our understanding of the environmental endocrine disruption issue and recommends a few research needs. Finally, the report states the U.S. Environmental Protection Agency Science Policy Council's interim position on endocrine disruption and lists some of the ongoing activities to deal with this matter.
Role of Aldose Reductase and Oxidative Damage in Diabetes and the Consequent Potential for Therapeutic Options
Authors: Satish K. Srivastava, Kota V. Ramana, Aruni Bhatnagar
Journal: Endocrine Reviews (2005)

Aldose reductase (AR) is widely expressed aldehyde-metabolizing enzyme. The reduction of glucose by the AR-catalyzed polyol pathway has been linked to the development of secondary diabetic complications. Although treatment with AR inhibitors has been shown to prevent tissue injury in animal models of diabetes, the clinical efficacy of these drugs remains to be established. Recent studies suggest that glucose may be an incidental substrate of AR, which appears to be more adept in catalyzing the reduction of a wide range of aldehydes generated from lipid peroxidation. Moreover, inhibition of the enzyme has been shown to increase inflammation-induced vascular oxidative stress and prevent myocardial protection associated with the late phase of ischemic preconditioning. On the basis of these studies, several investigators have ascribed an important antioxidant role to the enzyme. Additionally, ongoing work indicates that AR is a critical component of intracellular signaling, and inhibition of the enzyme prevents high glucose-, cytokine-, or growth factor-induced activation of protein kinase C and nuclear factor-κ-binding protein. Thus, treatment with AR inhibitors prevents vascular smooth muscle cell growth and endothelial cell apoptosis in culture and inflammation and restenosis in vivo. Additional studies indicate that the antioxidant and signaling roles of AR are interlinked and that AR regulates protein kinase C and nuclear factor-κB via redox-sensitive mechanisms. These data underscore the need for reevaluating anti-AR interventions for the treatment of diabetic complications. Potentially, the development of newer drugs that selectively inhibit ARmediated glucose metabolism and signaling, without affecting aldehyde detoxification, may be useful in preventing inflammation associated with the development of diabetic complications, particularly micro- and macrovascular diseases.
Routine home treatment of deep vein thrombosis
Authors: J. Eikelboom
Journal: BMJ (2001)

Papers p 1212 

Heparin therapy for at least five days followed by long term oral anticoagulation has been the standard care for patients with acute deep vein thrombosis.1 Initiation of treatment usually requires patients to be admitted to hospital for administration of intravenous unfractionated heparin and dose adjustment according to the results of the activated partial thromboplastin time. However, the emergence of low molecular weight heparin as a safe, effective, and convenient treatment for deep vein thrombosis has challenged the need for routine admission. A paper in this week's issue adds to the evidence that home treatment of deep vein thrombosis is now routinely feasible (p 1212).2

Aggregate data from a recent meta-analysis of randomised trials,3 also summarised in a Cochrane systematic review,4 show that low molecular weight heparin is at least as effective and safe as unfractionated heparin for the initial treatment of deep vein thrombosis. Unlike unfractionated heparin, which is usually given by continuous intravenous infusion, low molecular weight heparin can be given subcutaneously in a fixed, weight adjusted dose without the need for laboratory …
Randomised placebo-controlled study of stopping second-line drugs in rheumatoid arthritis
Authors: S. ten Wolde, F.C. Breedveld, B.A.C. Dijkmans, J. Hermans, J.P. Vandenbroucke, M.A.F.J. van de Laar, H.M. Markusse, M. Janssen, H.R. van den Brink
Journal: The Lancet (1996)
Longterm appraisal of the histological appearances of the ileal reservoir mucosa after restorative proctocolectomy for ulcerative colitis.
Authors: P Setti Carraro, I C Talbot, R J Nicholls
Journal: Gut (1994)

Between November 1976 and December 1985, 110 patients had restorative proctocolectomy for ulcerative colitis. The histological appearances in the reservoir mucosa were followed up in 60 of 109 survivors over 19-173 months (median 97). The median number of biopsy specimens taken per patient was six with a range of 3-13. These were examined by one pathologist (ICT) unaware of the clinical details using a scoring system previously described to assess the degree of chronic and acute inflammation. There was a significant correlation between the degree of severity of chronic and acute changes (r = 0.6192, p &lt; 0.000001). There was no correlation between the severity of inflammation and the following variables: preoperative duration of disease, presence of cancer or dysplasia in the original operative specimen, extra-alimentary manifestations or the type of reservoir. A significant correlation between severe inflammation and male sex was found (p &lt; 0.035). The 60 patients could be divided into three groups based on the severity and fluctuation of histological inflammation. In group A (n = 27, 45%) chronic changes were minor and acute inflammation was never seen. In group B (n = 25, 42%) chronic changes were more severe and there were transient episodes of acute inflammation. In group C (n = 8, 13%) severe chronic and severe acute inflammation were constantly present. Differentiation of the three groups had clearly occurred within six months from closure of the ileostomy. Patients in group C could be identified on histological criteria within weeks of closure of the ileostomy and were those exclusively at risk of developing chronic pouchitis. Chronic pouchitis never occurred in patients of groups A and B. No case of dysplasia was seen. Histological assessment of the reservoir mucosa with in a few months after closure of the ileostomy seems to define patients who will and who will not subsequently develop pouchitis.
Reactivation of Cytomegalovirus Infection in Critically Ill Immunocompetent Patients—Reply
Authors: Ajit P. Limaye, Wendy M. Leisenring, Michael Boeckh
Journal: JAMA (2008)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Nitrofurantoin in Chronic Urinary Infection Associated with Renal Calculi
Authors: M. G. McGeown
Journal: BMJ (1956)

In the recent literature there have been numerous references to the use of nitrofurantoin (N-(5-nitro-2-furfurylidene)-1-aminohydantoin; "furadantin") in the treat- ment of urinary infections.Many reports consist of series of cases of urinary infection, both acute and chronic, associated with varying complicating factors such as urinary stasis, prostatectomy, or urolithiasis, which greatly increase the difficulty in interpreting the results of therapy (Norfleet et al., 1953 ; Kaplan and
SCHIZOPHRENIA AND DIABETES
Authors: EDWIN KASIN, SAM PARKER
Journal: American Journal of Psychiatry (1943)

1. We have presented a detailed clinical report of a case of schizophrenia associated with a true diabetes mellitus. 2. Analysis of the literature and clinical experience reveals such a combination to be extremely rare, our case being but the second definitive one recorded. 3. We have commented briefly on the psychosomatic and constitutional significance of this clinical combination of diseases.
Humoral Basis for Gastric Hypersecretion After Portacaval Shunting
Authors: Ward O. Griffen
Journal: JAMA (1965)

Is the evidence conclusive that gastric hypersecretion following portacaval shunting is of a humoral nature? Experimental data so far supports this concept, but definite proof is still lacking. Gastric hypersecretion from vagally-denervated pouches in dogs with portacaval shunts can be explained by at least two factors other than a humoral mechanism: (1) Heidenhain pouches retain sympathetic innervation which may be an efferent pathway for a stimulating factor; (2) the venousdrainage of these pouches, an integral part of the portal venous system, by changing blood flow rate following portacaval shunting, may induce changes in their secretory pattern. These two factors are eliminated by transplanting vagally-denervated pouches into the abdominal wall. When the original neurovascular pedicle to the pouch is transected, the sympathetic pathway is interrupted and the venous drainage of the pouch is completely independent of the portal venous system. This report presents the secretory data for such pouches before and
Defective migration of neuroendocrine GnRH cells in human arrhinencephalic conditions
Authors: Luis Teixeira, Fabien Guimiot, Catherine Dodé, Catherine Fallet-Bianco, Robert P. Millar, Anne-Lise Delezoide, Jean-Pierre Hardelin
Journal: Journal of Clinical Investigation (2010)

Patients with Kallmann syndrome (KS) have hypogonadotropic hypogonadism caused by a deficiency of gonadotropin-releasing hormone (GnRH) and a defective sense of smell related to olfactory bulb aplasia. Based on the findings in a fetus affected by the X chromosome–linked form of the disease, it has been suggested that hypogonadism in KS results from the failed embryonic migration of neuroendocrine GnRH1 cells from the nasal epithelium to the forebrain. We asked whether this singular observation might extend to other developmental disorders that also include arrhinencephaly. We therefore studied the location of GnRH1 cells in fetuses affected by different arrhinencephalic disorders, specifically X-linked KS, CHARGE syndrome, trisomy 13, and trisomy 18, using immunohistochemistry. Few or no neuroendocrine GnRH1 cells were detected in the preoptic and hypothalamic regions of all arrhinencephalic fetuses, whereas large numbers of these cells were present in control fetuses. In all arrhinencephalic fetuses, many GnRH1 cells were present in the frontonasal region, the first part of their migratory path, as were interrupted olfactory nerve fibers that formed bilateral neuromas. Our findings define a pathological sequence whereby a lack of migration of neuroendocrine GnRH cells stems from the primary embryonic failure of peripheral olfactory structures. This can occur either alone, as in isolated KS, or as part of a pleiotropic disease, such as CHARGE syndrome, trisomy 13, and trisomy 18.
Contraction and endothelium dependent relaxation via a adrenoceptors are variable in various pig arteries
Authors: M. Ohgushi, H. Yasue, K. Kugiyama, T. Murohara, N. Sakaino
Journal: Cardiovascular Research (1993)

Objective: The aim was to examine differences in the vascular response to α adrenoceptor stimulation on both smooth muscle and endothelium among large arteries perfusing various organs. Methods: In ring preparations of coronary, carotid, iliac, mesenteric, and renal arteries from pigs (n=24), the magnitudes of contraction to noradrenaline (with β blocker), with or without endothelium, and endothelium dependent relaxation to noradrenaline (with α1 and β blocker) were compared in vitro. Results: In both endothelium-intact and denuded groups, the contractions to noradrenaline were significantly smaller in coronary and carotid arteries than in iliac, mesenteric, and renal arteries. The presence of endothelium significantly suppressed the contractions in coronary and carotid arteries, but did not affect the contractions in iliac, mesenteric, and renal arteries. The endothelium dependent relaxations to noradrenaline, which were abolished by LNMMA, were more prominent in coronary and carotid arteries than in iliac, mesenteric, and renal arteries. Conclusions: The contractions via α adrenoceptors were small, and endothelium dependent relaxations via α2 adrenoceptors were large, in the coronary and carotid arteries, which perfuse the vital organs (heart and brain), as compared with those in iliac, mesenteric, and renal arteries. These results suggest that in the state of activation of the sympathetic nervous system, arterial tone in response to α adrenoceptor stimulation may be regulated not only by α adrenoceptors on vascular smooth muscle but also by those on endothelium, through release of endothelium derived relaxing factor (EDRF) via α2 adrenoceptors. Cardiovascular Research 1993;27:779-784
Sex Differences of Endogenous Sex Hormones and Risk of Type 2 Diabetes
Authors: Eric L. Ding, Yiqing Song, Vasanti S. Malik, Simin Liu
Journal: JAMA (2006)

Inconsistent data suggest that endogenous sex hormones may have a role in sex-dependent etiologies of type 2 diabetes, such that hyperandrogenism may increase risk in women while decreasing risk in men.To systematically assess studies evaluating the association of plasma levels of testosterone, sex hormone-binding globulin (SHBG), and estradiol with risk of type 2 diabetes.Systematic search of EMBASE and MEDLINE (1966-June 2005) for English-language articles using the keywords diabetes, testosterone, sex-hormone-binding-globulin, and estradiol; references of retrieved articles; and direct author contact.From 80 retrieved articles, 43 prospective and cross-sectional studies were identified, comprising 6974 women and 6427 men and presenting relative risks (RRs) or hormone levels for cases and controls.Information on study design, participant characteristics, hormone levels, and risk estimates were independently extracted by 2 investigators using a standardized protocol.Results were pooled using random effects and meta-regressions. Cross-sectional studies indicated that testosterone level was significantly lower in men with type 2 diabetes (mean difference, -76.6 ng/dL; 95% confidence interval [CI], -99.4 to -53.6) and higher in women with type 2 diabetes compared with controls (mean difference, 6.1 ng/dL; 95% CI, 2.3 to 10.1) (P<.001 for sex difference). Similarly, prospective studies showed that men with higher testosterone levels (range, 449.6-605.2 ng/dL) had a 42% lower risk of type 2 diabetes (RR, 0.58; 95% CI, 0.39 to 0.87), while there was suggestion that testosterone increased risk in women (P = .06 for sex difference). Cross-sectional and prospective studies both found that SHBG was more protective in women than in men (P< or =.01 for sex difference for both), with prospective studies indicating that women with higher SHBG levels (>60 vs < or =60 nmol/L) had an 80% lower risk of type 2 diabetes (RR, 0.20; 95% CI, 0.12 to 0.30), while men with higher SHBG levels (>28.3 vs < or =28.3 nmol/L) had a 52% lower risk (RR, 0.48; 95% CI, 0.33 to 0.69). Estradiol levels were elevated among men and postmenopausal women with diabetes compared with controls (P = .007).This systematic review indicates that endogenous sex hormones may differentially modulate glycemic status and risk of type 2 diabetes in men and women. High testosterone levels are associated with higher risk of type 2 diabetes in women but with lower risk in men; the inverse association of SHBG with risk was stronger in women than in men.
Gene expression analysis during dengue virus infection in HepG2 cells reveals virus control of innate immune response
Authors: Thaís M. Conceição, Tatiana El-Bacha, Camila S.A. Villas-Bôas, Gerardo Coello, Jorge Ramírez, Monica Montero-Lomeli, Andrea T. Da Poian
Journal: Journal of Infection (2009)
NOTES ON RECENT CASES OF EXTRA-GENITAL SYPHILITIC INFECTION.
Authors: L. DUNCAN BULKLEY
Journal: JAMA (1902)

At the meeting of this Section last year<sup>1</sup>I called especial attention to syphilis as a non-venereal disease, as observed in marital syphilis, hereditary syphilis, and that acquired by means of innocent extra-genital infection; the latter in social and industrial life, in the care of children, and in professional care of the sick. The instances where the disease has been in some manner innocently acquired, which have fallen under my personal observation and care, now number many hundreds, and there are constant additions. The subject of marital and hereditary syphilis is a large and interesting one, but must be illustrated on another occasion. At present it is desired to call attention to the rather frequent occurrence of extra-genital infection, as indicated by the relatively considerable number of eases which have come under my care in private and public practice during the past year, or rather since Jan. 1, 1900.