tbuckley/cabot-search huggingface dataset:
SP0143 Progranulin meets TNF in inflammatory arthritis
Authors: C. Liu
Journal: Annals of the Rheumatic Diseases (2013)

Tumor necrosis factor-a (TNFa) has received the greatest attention because of its position at the apex of the pro-inflammatory cytokine cascade, and its dominance in the pathogenesis of inflammation. Anti-TNF therapies have been accepted as the effective approach to treating rheumatoid arthritis. In a global screen for the binding proteins of progranulin (PGRN), an autocrine growth factor with multiple functions, we found that PGRN bound to TNFR1 and TNFR2. PGRN-deficient mice were susceptible to collagen-induced arthritis, and administration of PGRN reversed inflammatory arthritis. More importantly, Atsttrin, an engineered protein composed of three PGRN fragments, exhibited potent anti-inflammatory activity, which surpassed PGRN itself, <i>in vivo</i>. This talk will focus on the interplay between PGRN and TNF in inflammatory arthritis as well as the immunological mechanism involved. The talk will also highlight Atsttrin. Identification of PGRN as a ligand of TNFR and an antagonist of TNFα signaling not only betters our understanding of the pathogenesis of inflammatory arthritis, but also provides new therapeutic interventions for various TNFα-mediated pathologies and conditions, including rheumatoid arthritis. <h3>Disclosure of Interest</h3> None Declared
Case 21-2001
Authors: Allan H. Ropper, Anat Stemmer-Rachamimov
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 31-year-old man was admitted to the hospital because of an apparent seizure and radiologic evidence of a cerebral lesion.The patient had been in excellent health until five days earlier, when he felt weak, was briefly unable to walk, and began to have mild headaches and dizzy spells, which lasted for several days. A computed tomographic (CT) scan of the head, obtained elsewhere, showed a hypodense lesion in the right parietal lobe. On the day of admission, uncontrollable flailing of the right arm and leg developed. The patient was referred to this hospital.The patient was . . .
Malpractice Threat Is Daunting, Real
Authors: David Artz, Elaine Blume
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Malpractice Threat Is Daunting, Real Get access David Artz, David Artz Search for other works by this author on: Oxford Academic PubMed Google Scholar Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 17, 4 September 1991, Page 1208, https://doi.org/10.1093/jnci/83.17.1208 Published: 04 September 1991
Abstract 5163: MMP3 increases expression of CXCL7.
Authors: Donghong Ju, Mary A. Kosir
Journal: Cancer Research (2013)

Abstract MMP3 leads to epithelial-mesenchymal transformation (EMT) and malignant transformation of cultured cells. Previously, increased expression of the CXC chemokine CXCL7 was associated with EMT. The hypothesis tested is that MMP3 increases the expression of CXCL7 Methods: Human breast cells (MCF10AT (proliferative), MCFDCIS.com (in situ), MCFCA1a (malignant)) cultured in serum free medium were exposed to MMP-3 for 4 days, and washed 3 times with PBS, then cultured in MMP-3 free condition medium for three more days. Cells were collected every day for RNA extraction, and analyzed for relative CXCL7 gene expression using RT real time PCR. Cells sampled from day 0 were used as control to normalize the results. GADPH was control. Cells culture supernatant also collected every day for CXCL7 protein level expression. Protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA) using human CXCL7/NAP-2 Duo set ELISA Development System. Measurements were done in triplicate; results are representative of three experiments. Results: When exposed to MMP-3, the CXCL7 RNA level increased MCF-10AT cells RNA level increased 1.5 fold, and there was no change in CXCL7 protein level in MCF-10AT cells. For MCFDCIS.com cells, the CXCL7 RNA level increased 2.5 fold, and CXCL7 protein level increased 1.6 fold. For MCFCA1a cells, the CXCL7 RNA level increased 2.6 fold, CXCL7 protein level increased 1.5 fold. The peak expression was 3-4 days. Removal of MMP-3 caused CXCL7 expression to return back to baseline in MCF10AT, DCIS.com and malignant Ca.cl1 cells. Conclusion: The expression of chemokine CXCL7 in breast cell (MCF10AT, DCIS.com, MCFCA1a) was up regulated at both on RNA and protein level (except for MCF10AT) when exposed to MMP-3, and removal of MMP-3 caused CXCL7 expression to return to baseline. The stromal influence by MMP3 on breast cells and breast cancer cells may direct further progression toward the malignant phenotype and provides another therapeutic pathway target. Citation Format: Donghong Ju, Mary A. Kosir. MMP3 increases expression of CXCL7. [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 5163. doi:10.1158/1538-7445.AM2013-5163
Lipomodelling of the breast.
Authors: D ELFadl, T Mahapatra, P McManus, P Drew
Journal: Cancer Research (2009)

Abstract Abstract #4149 Background: Lipomodelling is the autologous transfer of fat to correct congenital and post-surgical deformities. Recent improvements in technique have provided the opportunity for a greater volume of fat transfer thus increasing its potential application following surgery for benign and malignant breast disease.&amp;#x2028; Materials &amp; methods: After injecting a solution of local anaesthetic, normal saline and 1:106 adrenaline into donor sites in the abdomen and thighs, fat was aspirated with 3mm cannulae and centrifuged for 5 minutes. The fat was then re-injected into pre-marked areas in the breast using a 3mm injection cannula. Patients were followed up in a specialist breast clinic.&amp;#x2028; Results: 23 patients (22 female, 1 male) were treated between November 2007 and May 2008. The mean age was 50.6 years (36-61).&amp;#x2028; &amp;#x2028; Prior to lipomodelling, volume deficit was observed in all patients. A visible depression was identified in 43.5% (n=10), significant flap atrophy in 21.7% (n=5), skin tethering in 21.7% (n=5) and implant rippling in 13% (n=3). Ten patients (43.5%) required lipomodelling to the upper pole, while in 7 patients (30.4%), the location was closely associated with the surgical scar.&amp;#x2028; The average volume of fat harvested was 210.7 ml (85-510), and that injected per breast was 107.1 ml (45-206). Injections were stopped when slight overfilling was observed. Excessive tissue tension was avoided. Operative time varied between 45-100 minutes.&amp;#x2028; During the first follow up visit, satisfactory results were recorded. 3 patients were booked for their second operation.&amp;#x2028; Nine patients were seen at 3-4 months (second follow up visit). Two patients had clinical and radiological evidence of fat necrosis. One patient had marked volume resorption and numbness at the donor site. Eight patients had good volume retention. Two patients were booked for further lipomodelling at this stage.&amp;#x2028; One patient had further lipomodelling five months after the first session, with satisfactory results, and is awaiting a third session.&amp;#x2028; &amp;#x2028; Discussion: Early results have shown satisfactory cosmetic outcome and patient satisfaction. The technical simplicity and autologous nature make lipomodelling an attractive option to both surgeon and patient. However it is not universally successful and further follow-up is required before the long term effects of the technique in cancer patients can be confirmed. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4149.
Association of an Isomeric Species of Carcinoembryonic Antigen with Neoplasia of the Gastrointestinal Tract
Authors: Thomas S. Edgington, Robert W. Astarita, Edward F. Plow
Journal: New England Journal of Medicine (1975)

We studied the association between serum levels of an isomeric species of carcinoembryonic antigen and neoplasia of the gastrointestinal tract in 993 patients. With use of an empirically determined threshold, the antigen was found to be elevated in 80.4 per cent of 138 patients with neoplasia of the gastrointestinal tract. In contrast, it was elevated in only 9.3 per cent of other tumors, predominantly lung and breast tumors. Serum levels were elevated in 0.23 per cent of random patients and 0.41 per cent of 725 patients without neoplasia, including those with liver disease, inflammatory bowel disease and chronic renal disease. The results of this study suggest that this species of carcinoembryonic antigen may be a tumor-dominant isomer of carcinoembryonic antigen, and that assay for it offers an improved approach to the diagnosis and management of neoplasia of the gastrointestinal tract. (N Engl J Med 293:103–107, 1975)
Abstract 2575: Differential anti-tumor activities of curcumin against apoptosis and cell Cycle progression in Src- and Ras-activated human gallbladder carcinoma cells.
Authors: Misaki Ono, Takako Higuchi, Mikako Takeshima, Chen Chen, Shuji Nakano
Journal: Cancer Research (2013)

Abstract Curcumin, a phytochemical in turmeric, has been studied as a potential anticancer drug targeting multiple signaling molecules. However, the role of Src and Ras signaling pathways in curcumin sensitivity remains unknown. We investigated therefore the molecular mechanism of anti-proliferative and apoptosis-inducing activities of curcumin in HAG-1 human gallbladder adenocarcinoma cells transfected with either activated Src (HAG/src3-1) or Ras (HAG/ras5-1). Effects of curcumin on proliferation, apoptosis, cell cycle perturbation, and signal proteins for survival, proliferation, and apoptosis were evaluated by WST-1 assay, FACS analyses and Western blotting. Activation of either Src or Ras did not confer resistance to curcumin compared to HAG/neo3-5 vehicle-transfected cells, producing similar IC50 concentrations of curcumin among these 3 cell lines. Upon treatment with curcumin, constitutive activities of Erk1/2 were enhanced, but those of Akt were significantly inhibited in these three cell lines, with subsequent reductions of activities of downstream mTOR and S6K1. The sub-G0/G1 apoptotic cell populations were substantially increased in all cell lines with demonstrable cleavage of PARP, but this increase was most prominent in Src-activated cells. Reduced expression and phosphorylation of Bcl-2 and enhanced expression of Bax were demonstrated to have a causative role for the curcumin-induced apoptosis in Src-driven, but not Ras-driven cells. By contrast, drastic increases of the proportion of cells in a G2/M phase were seen in Ras-activated cells, suggesting a potential role of Ras/Erk1/2 activation in curcumin-induced G2/M cell cycle arrest. These data indicate that curcumin-induced growth declines would be mediated mainly by G2/M arrest of the cell cycle in Ras-driven cells but by apoptosis induction in Src-driven cells. Taken together, the results indicate that curcumin exhibits differential activities against apoptosis and cell cycle progression, depending on activation mechanisms of signal transduction, and that curcumin can overcome Src- and Ras-driven activation of downstream signaling pathways, thus providing evidence of potential application of curcumin for the treatment of human cancers with activated Src or Ras. Citation Format: Misaki Ono, Takako Higuchi, Mikako Takeshima, Chen Chen, Shuji Nakano. Differential anti-tumor activities of curcumin against apoptosis and cell Cycle progression in Src- and Ras-activated human gallbladder carcinoma cells. [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 2575. doi:10.1158/1538-7445.AM2013-2575
PTU-156 The Combination of Autofluorescence Imaging and Probe-Based Confocal Laser Endomicroscopy has an Excellent Diagnostic Accuracy for Dysplasia in Barrett’S Esophagus
Authors: M Di Pietro, E Bird-Lieberman, X Liu, M O’Donovan, R C Fitzgerald
Journal: Gut (2013)

<h3>Introduction</h3> Endoscopic surveillance in Barrett’s oesophagus (BO) has major limitations including sampling error due to inconspicuous dysplasia, need for multiple biopsies and subjectivity of pathological assessment of dysplasia. Probe-based confocal laser endomicroscopy (pCLE) allows real time histological assessment of the esophageal epithelium. However, in the absence of visible lesions, random pCLE is, like biopsies, subject to sampling error. We therefore used autofluorescence imaging (AFI) as a red-flag technique followed by a comparison of different advanced imaging technologies in these areas. The aims of the study were to evaluate the diagnostic accuracy for dysplasia of pCLE and to compare pCLE with narrow band imaging (NBI) for the prediction of the dysplasia. <h3>Methods</h3> 27 patients with BO have been recruited at a single tertiary referral centre (non-dysplastic BO n = 9, indefinite for dysplasia n = 2, BO with low grade dysplasia n = 8, BO with high grade dysplasia (HGD) n = 3, BO with intramucosal cancer (IMC) n = 5). Mean BO length was 8cm. AFI positive (AFI+) areas were identified and assessed by NBI-zoom and pCLE, according to previously published criteria. Targeted biopsies were taken from AFI+ areas as well as from random quadrantic locations. Correlation between imaging patterns and histological outcome was analysed in a per lesion analysis (AFI+ areas individually) and per patient analysis (overall histology). Differences between pCLE and NBI were analysed with Fisher’s exact test <h3>Results</h3> In the per lesion analysis, sensitivity and specificity of pCLE were 100% and 67%, respectively, for a diagnosis of HGD/IMC and 69% and 78% for a diagnosis of any grade of dysplasia. pCLE had a significantly higher sensitivity for dysplasia (P = 0.007) than NBI, but a lower specificity (p = 0.04), due to a slightly higher false positive rate. In the per patient analysis the combination of AFI and pCLE had a sensitivity and a specificity of 100% and 47%, respectively for a diagnosis of HGD/IMC, and 100% sensitivity and specificity for a diagnosis of any dysplasia (Table 1). AFI+pCLE did not change the overall patient outcome compared to the Seattle protocol, but allowed identification and correct characterization of 4 additional areas containing HGD/IMC <h3>Conclusion</h3> pCLE can efficiently identify any grade of dysplasia. These preliminary data suggest that the combination of AFI and pCLE allows accurate in vivo diagnosis of dysplasia within BO. A larger study is warranted to determine whether this approach afford the potential to eliminate the necessity for multiple random biopsies during endoscopic surveillance <h3>Disclosure of Interest</h3> None Declared
Large Community Outbreak of Cryptosporidiosis Due to Contamination of a Filtered Public Water Supply
Authors: E B Hayes, T D Matte, T R O'Brien, T W McKinley, G S Logsdon, J B Rose, B L Ungar, D M Word, P F Pinsky, M L Cummings
Journal: New England Journal of Medicine (1989)

Between January 12 and February 7, 1987, an outbreak of gastroenteritis affected an estimated 13,000 people in a county of 64,900 residents in western Georgia. Cryptosporidium oocysts were identified in the stools of 58 of 147 patients with gastroenteritis (39 percent) tested during the outbreak. Studies for bacterial, viral, and other parasitic pathogens failed to implicate any other agent. In a random telephone survey, 299 of 489 household members exposed to the public water supply (61 percent) reported gastrointestinal illness, as compared with 64 of 322 (20 percent) who were not exposed (relative risk, 3.1; 95 percent confidence interval, 2.4 to 3.9). The prevalence of IgG to cryptosporidium was significantly higher among exposed respondents to the survey who had become ill than among nonresident controls. Cryptosporidium oocysts were identified in samples of treated public water with use of a monoclonal-antibody test. Although the sand-filtered and chlorinated water system met all regulatory-agency quality standards, sub-optimal flocculation and filtration probably allowed the parasite to pass into the drinking-water supply. Low-level cryptosporidium infection in cattle in the watershed and a sewage overflow were considered as possible contributors to the contamination of the surface-water supply. We conclude that current standards for the treatment of public water supplies may not prevent the contamination of drinking water by cryptosporidium, with consequent outbreaks of cryptosporidiosis.
Familial Spastic Paraparesis Syndrome Associated with HTLV-I Infection
Authors: Edgar F. Salazar-Grueso, Timothy J. Holzer, Robin A. Gutierrez, James M. Casey, S.M. Desai, Sushil G. Devare, George Dawson, Raymond P. Roos
Journal: New England Journal of Medicine (1990)

HUMAN T-cell lymphotropic virus Type I (HTLV-I) is a retrovirus identified as the etiologic agent of adult T-cell leukemia and lymphoma.1 , 2 More recently, HTLV-I infection has been implicated in the causation of chronic progressive myelopathies, such as tropical spastic paraparesis3 , 4 and HTLV-I—associated myelopathy.5 HTLV-I—associated myelopathy affects patients from southern Japan, which has a temperate climate, whereas tropical spastic paraparesis affects persons from tropical areas. Despite these differences, the two conditions resemble each other,6 prompting some to suggest that they are different names for the same disease.7 HTLV-I has been implicated in the development of these conditions, because affected persons have . . .
Hemosuccus Pancreaticus in Glanzmann Thrombasthenia
Authors: Sina Izadyar, Gholamreza Toogeh, Mohammad Eftekhari, Ali Gholamrezanezhad
Journal: Clinical Nuclear Medicine (2011)

A 33-year-old man with Glanzmann thrombasthenia, enduring retractable melena, and with an active upper gastrointestinal bleeding (GIB) of unknown origin lasting intermittently for 6 months, was admitted. Abdominal ultrasound and computed tomography were not diagnostic. The patient underwent upper gastrointestinal endoscopy twice, both of which showed blood issuing forth from ampulla of vater and possible diagnoses of bleeding from papilla/hematobilia or hemosuccus pancreaticus were suspected. Digital subtraction angiography of celiac/superior mesenteric arteries was unremarkable. In GIB scintigraphy, a focus of activity appeared in the epigastric area early in the study (arrow), intensity of which increased gradually. Exploratory laparatomy confirmed the diagnosis of hemosuccus pancreaticus. Although the patient was doing well for few weeks after the surgery, he died 3 months later after an acute episode of severe GIB.
Case 9-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, B. Taylor Thompson, Eugene J. Mark
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 74-year-old man was admitted to the hospital after emesis and respiratory arrest.The patient had not sought medical attention for more than one year until the evening of admission, when he went to a nearby facility because of abdominal pain. Physical examination showed that the temperature was 38.6°C. The abdomen was tender, with guarding in the right lower quadrant. The white-cell count was 23,100. The potassium was 6.6 mmol per liter. An x-ray film of the chest (Fig. 1) revealed marked scarring and bullae in both upper lobes, with hilar retraction and apical pleural thickening; pleural . . .
FRONTAL LOBOTOMY
Authors: JANE E. OLTMAN, BERNARD S. BRODY, SAMUEL FRIEDMAN, WILLIAM F. GREEN
Journal: American Journal of Psychiatry (1949)

Since May, 1946, 107 patients have undergone frontal lobotomy at the Fairfield State Hospital. The group was composed almost entirely of individuals suffering from chronic mental illness whose prognosis seemed extremely unfavorable; 85% were schizophrenics. The average duration of mental illness was 7.4 years and of hospitalization, 4.4 years prior to operation. The results following lobotomy have been encouraging: 56.7% of the entire group exhibited significant improvement; thus far, 37.4% have been able to leave the hospital. The mortality rate was low and complications, except for convulsive seizures, have been relatively infrequent. Prognostic guides seem to consist chiefly of the type of illness and the character of symptomatology. Results were best in the nonschizophrenic group, next best in the paranoid, catatonic, and mixed types of schizophrenia, and poorest in simple and hebephrenic dementia præcox. Disturbed, aggressive, combative, and hostile patients appeared to receive maximum benefit. Duration of illness had relatively little significance as a prognostic guide. Lobotomy may be especially helpful in patients suffering from pulmonary tuberculosis, which is a specific contraindication to shock therapy. There is no reduction of intellectual functioning following operation; our patients who could be tested exhibited an average rise of 10 points on the Wechsler-Bellevue scale 6 months postoperatively. Lobotomy appears to be a fruitful method in the treatment of chronic mental disease.
Communicating with patients and the risks of cancer risk prediction.
Authors: JG Elmore
Journal: Cancer Research (2009)

Abstract Abstract #MS1-4 BACKGROUND&amp;#x2028; Patients may ask, “What is my risk of getting cancer?” and they may use cancer risk prediction models that are readily available on the web. Unfortunately, our risk models are less able to predict cancer at the level of the individual patient and our ability to communicate numeric information is limited.&amp;#x2028; ASSESSMENT OF RISK MODELS&amp;#x2028; Most cancer risk prediction models perform well at the population level. The calibration of risk prediction models is assessed at the population level by comparing the number of patients who the model estimated would develop cancer with the number of patients who actually were diagnosed with cancer.&amp;#x2028; Unfortunately, risk prediction models often fall short on their ability to discriminate at the level of the individual patient. The models are less able to separate individuals who are, and are not, going to develop diseases like cancer. Many “low risk” individuals develop cancer, while many “high-risk” individuals do not. Discrimination is the degree to which the estimates from the risk model are consistently higher for individuals who develop cancer, compared to those who do not develop cancer.&amp;#x2028; COMMUNICATION&amp;#x2028; Communicating information to individuals about their risk of developing cancer is challenging. There is a great deal of fear about cancer in the community and a heightened sense of risk. Much of the discussion about cancer risk is in terms of relative risks, which sound more threatening than absolute risk differences. Use of both positive and negative framing of the risk estimate numbers is helpful. However, the challenge of understanding numbers is not unique to patients; clinicians are also challenged with both understanding and communicating this information.&amp;#x2028; CONCLUSION&amp;#x2028; Although we have high-tech medical programs and decades of research on cancer, our ability to individually tailor cancer risk prediction tools is sorely lacking. Our current risk prediction models may be appropriate for educating patients about aggregate or population-level cancer risk statistics. However, patients should be counseled that the estimates say little about which specific individuals will develop cancer. We need to develop better risk prediction tools and tools that facilitate basic communication regarding risk and benefit. Both of these challenges may be difficult, but would be extremely worthwhile. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr MS1-4.