tbuckley/cabot-search huggingface dataset:
Abstract 1046: Molecular link between HER2 and epithelial-to-mesenchymal transition in breast cancer
Authors: Parul Gupta, Sanjay K. Srivastava
Journal: Cancer Research (2014)

Abstract Breast cancer is a second most lethal form of cancer. Metastasis is responsible for about 90% of cancer- related deaths. Metastasis is a multi-step process and epithelial to mesenchymal transition (EMT) is the initiating step. HER2 is overexpressed in about 25-30% of breast cancer patients and responsible for poor prognosis. Our results show a novel role of HER2 in inducing EMT in breast cancer cells. To delineate the mechanism of EMT and role of HER2, we used MDA-MB-231, MCF-7 breast cancer cells with their syngeneic variants having stable HER2 overexpression (referred to as high HER2 or HH cells) and 4T-1 cells. The Boyden's chamber assay showed that HH cells were more invasive than the parent cells. The higher invasive potential of cells was accompanied with increased expression of mesenchymal markers like N-cadherin, along with suppression of epithelial markers like Cytokeratin-18. HER2 overexpression was also associated with enhanced expression of transcription factors like SNAIL and ZEB-1 that orchestrate the process of EMT. It is known that TGFβ is a master regulator of EMT process in cancer cells. Interestingly, HH cells exhibited higher levels of TGFβ protein and mRNA levels along with increased expression of SMADs relative to the parent cell lines. SMADs are the classical downstream effector molecules for TGFβ. Hence these results indicate that HER2 overexpression modulates TGFβ signaling to promote the process of EMT. In addition, induction of SNAIL, TGFβ and SMAD4 by heregulin treatment further established the role of HER2 in EMT process. To confirm the requirement of HER2 in the maintenance of mesenchymal traits, we silenced HER2 in MDA-MB-231 and MDA-MB-231 (HH) cells. HER2 silencing suppressed the invasion and mesenchymal markers indicating a direct connection of EMT with HER2 in breast cancer cells. Taken together our results for the first time provides a molecular evidence for the regulation of EMT by HER2 through TGFβ signaling. Further mechanistic and pre-clinical in vivo studies are under progress. [Supported in part by R01 grant CA129038 (to S.K.S) awarded by the National Cancer Institute]. Citation Format: Parul Gupta, Sanjay K. Srivastava. Molecular link between HER2 and epithelial-to-mesenchymal transition in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1046. doi:10.1158/1538-7445.AM2014-1046
Down-regulation of CD9 in Human Ovarian Carcinoma Cell Might Contribute to Peritoneal Dissemination: Morphologic Alteration and Reduced Expression of β1 Integrin Subsets
Authors: Mitsuko Furuya, Hiroaki Kato, Norihiro Nishimura, Isamu Ishiwata, Hitoshi Ikeda, Ryoko Ito, Takashi Yoshiki, Hiroshi Ishikura
Journal: Cancer Research (2005)

Abstract Peritoneal dissemination is one of the main causes of death in cancer patients. Pathophysiology of metastasis has been well investigated, but the mechanism of diffuse spread of tumor colonies in the peritoneal cavity is not fully understood. CD9 is a member of tetraspanin and its down-regulation is known to be involved in poor prognosis. To investigate the significance of the down-regulation of CD9, HTOA, an ovarian carcinoma cell line that highly expressed CD9, was transiently transfected with small interfering RNA (siRNA) against CD9, and CD9-negative cells (HTOACD9−) were purified. HTOACD9− showed altered adhesion patterns on Matrigel, collagen, fibronectin, and laminin compared with those of control siRNA–transfected HTOA (control-HTOA). Flow cytometry and fluorescence cytostainings revealed that the expression levels of integrins β1, α2, α3β1, α5, and α6 were lower in HTOACD9− than those of control-HTOA. HTOACD9− showed altered expression of junctional and cytoskeletal molecules. By time-lapse video microscopy, control-HTOA showed solid adhesion to extracellular matrix and formed cobblestone pattern, whereas HTOACD9− showed weaker adhesion and were distributed as diffuse spots. To examine whether the expression level of CD9 change during tumor dissemination, HTOA-P, a highly disseminative subclone of HTOA, was established. HTOA-P showed distinctive down-regulation of CD9 at mRNA and protein levels, and showed similar morphologic alteration as HTOACD9− did. These findings indicate that the down-regulation of CD9 may be an acquired event in the process of tumor dissemination. Down-regulated CD9 may attenuate the expression of several integrins and rearrange junctional and cytoskeletal molecules that might contribute to dissemination of ovarian carcinomas.
Impaired antibody synthesis in patients with chronic hepatitis B infection
Authors: Marek J. Nowicki, Myron J. Tong, Prem V. Nair, Douglas Stevenson
Journal: Hepatology (1986)

In vitro synthesis of the anti–HBc, anti–HBs and polyclonal IgG and IgM classes of antibodies were determined from supernatants of peripheral blood mononuclear cells cultured in the presence of pokeweed mitogen. Thirty–seven patients with chronic hepatitis B and 10 healthy control subjects whose sera were positive for anti–HBs formed the study group. Twenty–four of 37 patients showed histologic evidence of chronic active hepatitis B while the remaining 13 patients had chronic persistent hepatitis B. Lymphocytes from chronic persistent hepatitis B, chronic active hepatitis B and healthy controls secreted similar levels of IgM. However, IgG synthesis was markedly impaired (p &lt; 0.002) in the chronic persistent hepatitis B group as compared with healthy controls or chronic active hepatitis B patients. In vitro anti–HBc production and serum anti–HBc titers correlated directly with hepatocellular inflammation and inversely with serum hepatitis B virus DNA. Anti–HBc synthesis was significantly higher in chronic active hepatitis B patients who exhibited a more pronounced hepatocellular damage when compared to chronic persistent hepatitis B patients who had little or no liver cell injury.
Talking With Patients: A Basic Clinical Skill
Authors: Barbara Bates
Journal: JAMA (1993)

British physicians have long been admired for their skills in physical examination, but their ability to communicate with patients may not have reached a comparable level. Among those who are making a concerted effort to change this situation are Philip R. Myerscough and some colleagues in Edinburgh and Glasgow. The second edition of Talking With Patients: A Basic Clinical Skill is meant primarily for students of medicine. Myerscough, an obstetrician-gynecologist, has written more than half of the book, and five additional contributors have each added chapters that draw from their fields of general practice, pediatrics, adolescent psychiatry, geriatric medicine, and hospice care. The resulting volume is easy to read, light in the hand, and usefully illustrated with line drawings.  Most of the content will be familiar to physicians trained in US medical schools during the past 20 years. It includes professional and sick roles, types of communication, the ways to
Mucosal Immunity and Primary Biliary Cirrhosis: Presence of Antimitochondrial Antibodies in Urine
Authors: Atsushi Tanaka, Gregory Nalbandian, Patrick S.C. Leung, Gordon D. Benson, Santiago Munoz, Jorge A. Findor, Andrea D. Branch, Ross L. Coppel, Aftab A. Ansari, Eric M. Gershwin
Journal: Hepatology (2000)

We have shown that IgA–class antimitochondrial autoantibodies (AMA) can be detected in the bile and saliva of patients with PBC, suggesting that AMA are secreted into the luminal fluid across bile ducts and salivary glands. These data prompted us to determine whether AMA of the IgA isotype may be transported across other epithelial mucosa. Therefore, we tested for the presence of AMA in the urine specimens of 83 patients with PBC and 58 non–PBC controls including healthy individuals and patients with other liver diseases. Patients enrolled in this study had no history of renal disease, and we confirmed there was less than 50 μg/mL of protein in each of the urine specimens. Interestingly, we found that AMA were present in the urine of 71/83 (86%) of all patients with PBC and in 71/78 (91%) of patients with PBC that were serum AMA positive. In contrast, AMA were not detected in any of the 58 control urine specimens. Of particular interest, AMA of the IgA isotype was present in 57/83 (69%) of patients with PBC, and in 52 of these 57, we found secretory–type IgA. In a nested random subgroup of urine samples, the prevalence of the IgA2 AMA was 6/18 (33%), significantly lower than in matched serum samples, 13/16 (81%, P = .007). These data show that AMA of the IgA isotype is secreted into urine from the uroepithelium of patients with PBC, and support the thesis that PBC originated from either a mucosal challenge or a loss of mucosal tolerance.
Temporal sequence of splenic dysfunction in sickle cell disease
Authors: A.D. Adekile, A. Owunwanne, K. Al‐Za'abi, M.Z. Haider, M. Tuli, S. Al‐Mohannadi
Journal: American Journal of Hematology (2001)

Sickle cell patients develop splenic dysfunction early in the course of their disease as shown by failure to visualize the organ on technetium-99m colloid scintigraphy. However, preliminary studies from our center have shown that, when the spleen is not demonstrable on colloid uptake, it may be visualized on technetium-99m heat-denatured RBC scintigraphy. With time, however, the spleen can no longer be visualized with both tests in many patients. We have studied 46 patients aged 2 to 16 years, which included 36 SS, 7 Sbeta(0) thal, and 3 SD. Eighteen (39.1%) had normal splenic colloid uptake (Group 1), 15 (32.6%) had partial uptake (Group 2), and 13 (28.3%) had absent uptake (Group 3). When the patients in Group 1 were compared to those in the two other groups, there was no significant difference in the mean age and Hb F values. However, the mean Hb of 10.2 g/dl in Group 1 was significantly higher than the value of 9.0 g/dl in the other two groups. In addition, 60% of the SS patients with normal uptake and 40% of those with partial or absent uptake had co-existing alpha-thal trait; the difference in this proportion is significant (chi(2) = 85, P < 0.0001). Heat-denatured RBC scintigraphy was carried out on five patients in Group 2, and the spleen was visible in all, while of 12 children in Group 3, the spleen was visible only in 4 patients. This study demonstrates that the phagocytic function of the spleen, which is tested by colloid uptake, is the first to be lost while the filtration function, tested by denatured RBC uptake, persists for much longer. This finding may have significant implications for the clinical symptomatology and therapeutic strategies of sickle cell disease.
DYSPLASTIC GROWTH DIFFERENTIALS IN PATIENTS WITH PSYCHIATRIC DISORDERS: ASSESSMENT OF THE PROFILE OF EMOTIONAL IMMATURITY
Authors: JOHN W. LOVETT DOUST
Journal: American Journal of Psychiatry (1954)

1. A 99-item questionnaire is introduced to estimate the extent and dimensions of emotional immaturity or dysplasia in psychiatric patients. It is shown to be validly differentiating with respect to 260 healthy controls and 363 psychiatric patients classified in 6 diagnostic groups. Eighteen dimensions of the concept were tested and of these 13 proved to be statistically significant. 2. Chronological age and sex were found to be critical variables in addition to diagnosis and facilitated the extraction of an emotional maturity quotient, the "E.M.Q." Emotional immaturity lessens significantly with advancing years in all groups save schizophrenia and epilepsy but the growth potential is less for mentally sick patients than for the healthy controls. 3. The raw E.I. Scores and E.M.Q. showed a positive significant interdependance with "neuroticism" and with morphological growth estimates but a slight negative correlation with an I.Q. test.
Platelet-derived growth factor enhances in vitro erythropoiesis via stimulation of mesenchymal cells.
Authors: F Delwiche, E Raines, J Powell, R Ross, J Adamson
Journal: Journal of Clinical Investigation (1985)

The growth of erythroid colonies (from erythroid colony-forming cells) and erythroid bursts (from burst-forming cells [BFU-E]) is enhanced in the presence of serum as compared with plasma. A significant proportion of the enhanced growth is due to the platelet release product, platelet-derived growth factor (PDGF). Colony growth in cultures of whole marrow cells in platelet-poor plasma-derived serum (PDS) and erythropoietin was enhanced in a dose-dependent fashion by increasing concentrations of purified human PDGF with optimal enhancement at 12.5 ng/ml. However, no effect of platelet-release products or PDGF was observed on nonadherent human marrow cells or peripheral blood BFU-E, suggesting that an accessory cell population was required for the effect of PDGF on hematopoietic progenitors. In a two-layer culture system, pure populations of fibroblasts or smooth muscle cells, known to be present in the marrow microenvironment, restored the response of nonadherent marrow cells in the overlayer to PDGF and also conferred responsiveness to peripheral blood BFU-E. Endothelial cells in the two-layer culture system and macrophages, in contrast, lacked the ability to restore the enhancing effect of PDGF. Because other platelet-release mitogenic products are also found in serum, a monospecific anti-PDGF IgG preparation was added to cultures grown in platelet rich plasma-derived serum. Only partial reduction in colony and burst growth was seen, suggesting that other platelet-release products were acting in this system. These results demonstrate that PDGF enhancement of human hematopoietic progenitor cell growth requires mesenchymal cells, and provide an example and mechanism by which growth factors may influence hematopoietic progenitors via cells of the marrow microenvironment.
Nestle's response to concerns about oral rehydration solution
Authors: F. Haschke
Journal: BMJ (2010)

A Nestle maltodextrin based oral rehydration solution (ORS) has been sold under various trade names in several European countries. In all of these countries and for two decades this product has proved safe and efficacious as an ORS for treatment of diarrhoea and acute gastroenteritis. The product was introduced under the brand name Resorb Junior Plus in Sweden in 2009. In April 2010 Nestle decided to withdraw the product from the Swedish market because of reports of a few unexpected cases of worsening dehydration and hypernatremia during treatment of young children.1 (See also letter from Lidefelt and colleagues.2)

After a meeting between the Nestle Nutrition Institute and Karolinska Hospital, a collaboration was established to find the cause of the unexpected adverse reactions. A review of …
Receptors for human γG Globulin on human neutrophils
Authors: R. P. Messner, J. Jelinek
Journal: Journal of Clinical Investigation (1970)

Cell surface receptors for human γG antibodies directed against bacterial antigens were demonstrated on human neutrophils using an in vitro bacteriocidal-phagocytic assay. These results were confirmed by adherence of sensitized erythrocytes to monolayers of neutrophils or monocytes. Erythrocytes sensitized indirectly with antibacterial γG antibodies after passive sensitization with bacterial antigens adhered to both neutrophils and monocytes. Erythrocytes sensitized directly with conventional anti-D γG antibodies adhered only to monocytes, while those sensitized with the hyperimmune anti-CD γG antibody Ripley adhered to both monocytes and neutrophils. Adherence of anti-Rh or antibacterial γG antibodies to monocytes and neutrophils could be inhibited by whole γG, myeloma globulins of the γ1 or γ3 subclasses, or Fc fragments, but not by Fab fragment.
Obesity in US Children and Adults—Reply
Authors: Cynthia L. Ogden, Brian K. Kit, Katherine M. Flegal
Journal: JAMA (2012)

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
Cooperation of innate and adaptive immunity in the pathogenesis of biliary atresia: There's a killer on the run
Authors: Alexandra Sharland, Mark D. Gorrell
Journal: Hepatology (2009)

Biliary atresia is a neonatal obstructive cholangiopathy that progresses to end-stage liver disease. Although the etiology is unknown, a neonatal adaptive immune signature has been mechanistically linked to obstruction of the extrahepatic bile ducts. Here, we investigated the role of the innate immune response in the pathogenesis of biliary atresia. Analysis of livers of infants at diagnosis revealed that NK cells populate the vicinity of intrahepatic bile ducts and overexpress several genes involved in cytotoxicity. Using a model of rotavirus-induced biliary atresia in newborn mice, we found that activated NK cells also populated murine livers and were the most abundant cells in extrahepatic bile ducts at the time of obstruction. Rotavirus-primed hepatic NK cells lysed cholangiocytes in a contact- and Nkg2d-dependent fashion. Depletion of NK cells and blockade of Nkg2d each prevented injury of the duct epithelium after rotavirus infection, maintained continuity of duct lumen between the liver and duodenum, and enabled bile flow, despite the presence of virus in the tissue and the overexpression of proinflammatory cytokines. These findings identify NK cells as key initiators of cholangiocyte injury via Nkg2d and demonstrate that injury to the duct epithelium drives the phenotype of experimental biliary atresia.
Tumor necrosis factor‐α polymorphism in Turkish patients with dilated cardiomyopathy
Authors: Mehmet Alikasifoglu, Lale Tokgözoglu, Tayfun Acil, Enver Atalar, Mehmet Ali Oto, Süleyman Sirri Kes, Ergül Tuncbilek
Journal: European Journal of Heart Failure (2003)
Adult asthmatics sensitized to cats and dogs: symptoms, severity, and bronchial hyperresponsiveness in patients with furred animals at home and patients without these animals
Authors: P Plaschke, C Janson, B Balder, C Löwhagen, B Järvholm
Journal: Allergy (1999)

Background : Domestic furred animals are important sources of allergens in asthma, but few clinical studies have investigated the effects of exposure to or elimination of these allergens. The objective of this study was to investigate whether pet‐sensitized asthmatics with pets at home have worsened asthma, compared with similar asthmatics without pets. Methods : In a cross‐sectional epidemiologic study, 129 adult asthmatics sensitized to cats or dogs were investigated by interviews, skin prick tests, specific IgE, eosinophil counts, and bronchial methacholine challenge tests. Patients with a cat or dog at home ( n =39) were compared with subjects without pets ( n =90). Results : More subjects with pets had symptoms, inhaled or oral steroids, abnormal peak‐flow records, higher eosinophil counts, and a higher degree of bronchial hyperresponsiveness than subjects without pets. Asthmatics with pets more frequently ascribed their symptoms to their home environment, but fewer of them reported that their symptoms were elicited by contact with cats or dogs. Conclusions : This study strongly indicates that living with a cat or a dog aggravates symptoms and biomarkers of airway inflammation in asthmatics sensitized to cats or dogs. The study indicates that avoidance of these allergens may be an important measure in the treatment of sensitized asthmatics.
Health advisories for consumers of Great Lakes sport fish: is the message being received?
Authors: J Tilden, L P Hanrahan, H Anderson, C Palit, J Olson, W M Kenzie
Journal: Environmental Health Perspectives (1997)

Nationwide, 45 states issue health advisories for sport fish consumers. Chemical contaminants in some Great Lakes (GL) sport fish include compounds suspected of causing adverse reproductive and developmental effects. Although advisories to reduce consumption of contaminated fish, especially by women, have been issued by GL states (i.e., Illinois, Indiana, Michigan, Minnesota, New York, Ohio, Pennsylvania, and Wisconsin) since the mid-1970s, little is known about advisory awareness and GL sport fish consumption in the general population. To estimate the prevalence of GL sport fish consumption and health advisory awareness, we conducted a population-based telephone survey of 8,306 adult residents of the eight GL states. We gathered information concerning respondents' demographic characteristics, fish consumption during the preceding year, and sport fish consumption advisory awareness. The survey response rate was 69%. GL sport fish were eaten during the preceding year by 8.4% -95% confidence interval (CI), 7.6-9.2- of adults in the GL states, approximately 4.7 million persons. Women accounted for 43.9% (CI,39. 4-48.4) of consumers. Although 49.9% of GL sport fish consumers were aware of a health advisory, awareness varied significantly by sex: 58.2% (CI, 51.7-64.7) of males and 39.1% (CI, 32.6-45.6) of females were aware. Using logistic regression, we found awareness associated with male sex -odds ratio (OR) = 2.3; CI, 1.5-3.5), white race (OR = 4.2; CI, 1.9-9.1), college degree (OR = 3.1; CI, 1.3-7.6), and consuming >=24 GL sport fish meals/year (OR = 2.4; CI, 1.4-4.3). Only half of GL sport fish consumers reported awareness of a health advisory concerning eating GL sport fish. Awareness was especially low among women, suggesting the need of targeted risk communication programs for female consumers.
Careful Evaluation of CT Findings of a Cardiac Viability F-18 FDG PET/CT Study Leading to Detection of Esophageal Cancer
Authors: Asif Moinuddin, Nghi C. Nguyen, Medhat M. Osman
Journal: Clinical Nuclear Medicine (2010)

We present a case of esophageal adenocarcinoma as a follow-up for lesions seen on the computed tomography (CT) portion of a myocardial viability F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT study. A 64-year-old man presented with a history of prior myocardial infarctions, status post percutaneous transluminal coronary angioplasty, and multiple stent placements for viability evaluation. Limited CT images were viewed as part of the interpretation. Two densities, one in the left lower lung, pleural based, and another in the right retrocrural region were identified on CT images with suspicion for pathology. This was a FDG myocardial viability protocol; therefore, the true metabolic activity in these lesions cannot be assessed. For an F-18 FDG PET/CT myocardial viability protocol, glucose loading is desirable to ensure a predominant glucose substrate for the myocardium. However, for a cancer imaging protocol, 4 to 6 hours of fasting is required before FDG injection. After a discussion with the referring physician, further evaluation with whole body F-18 FDG PET/CT was scheduled for a later date, which additionally showed an esophageal lesion.