tbuckley/cabot-search huggingface dataset:
Clinical Medicine Meets Forensic Sciences
Authors: Rebecca Voelker
Journal: JAMA (1994)

LIKE A SLEUTH tracking an elusive killer, Charles Buerk, MD, still questions the death 2 years ago of a 39-year-old stabbing victim. The injury wasn't serious—a mild puncture wound in the left flank. But the victim died unexpectedly in the hospital 2 days later from adult respiratory distress syndrome (ARDS). Buerk, a trauma surgeon and director of surgical education at Orlando (Fla) Regional Medical Center, presented the case and several others at the annual meeting of the American Academy of Forensic Sciences in San Antonio, Tex. They illustrate how clinicians and medical examiners are collaborating to enhance quality assurance and ultimately improve patient care. Buerk recounted clues in the unexplained ARDS death. When the patient arrived at the emergency department within an hour after the stabbing, he was stable, alert, and oriented but his white blood cell count on admission was 30.0×10<sup>9</sup>/L. During repair of a small serosal
Caspase-1 Is a Direct Target Gene of ETS1 and Plays a Role in ETS1-Induced Apoptosis
Authors: Huiping Pei, Chunyang Li, Yair Adereth, Tien Hsu, Dennis K. Watson, Runzhao Li
Journal: Cancer Research (2005)

Abstract ETS1, the founding member of Ets transcriptional factor family, plays an important role in cell proliferation, differentiation, lymphoid cell development, transformation, angiogenesis, and apoptosis. Previous work has shown that ETS1 represses tumorigenicity of colon carcinoma cells in vivo, and that the p42-ETS1 protein bypasses a defect in apoptosis in colon carcinoma cells through the up-regulation of caspase-1 expression. In this report, we show that expression of p42-ETS1 inhibits tumorigenicity of colon cancer DLD-1 cells through induction of apoptosis in vivo. In support of the hypothesis that caspase-1 might be a target involved in the sensitization of DLD-1 cells to Fas-induced apoptosis by ETS1, overexpression of caspase-1 bypasses Fas-induced apoptosis in these cells as well. Furthermore, ETS1-mediated apoptosis was observed in MOP8 cells, a transformed mouse NIH3T3 cell line. To determine whether ETS1 activates the transcription of caspase-1, luciferase reporters driven by the wild-type and mutant caspase-1 promoters were generated. Both p51-ETS1 and p42-ETS1 transactivated the caspase-1 transcription and a functional Ets binding site is identified in the caspase-1 promoter. Wild-type caspase-1 promoter (pGL3-ICE) was strongly transactivated by ETS1 and this transactivation was dramatically diminished by the mutation of the potential Ets binding site (−525 bp). In addition, electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed complex formation between this binding site and ETS1 proteins. Taken together, ETS1 transcriptionally induces the expression of caspase-1; as such, the regulatory control of caspase-1 expression by ETS1 may underlie the apoptotic susceptibility modulated by ETS1 in specific tumor cells.
Natural History of Coronary Atherosclerosis by Multislice Computed Tomography
Authors: Stella-Lida Papadopoulou, Lisan A. Neefjes, Hector M. Garcia-Garcia, Willem-Jan Flu, Alexia Rossi, Anoeshka S. Dharampal, Pieter H. Kitslaar, Nico R. Mollet, Susan Veldhof, Koen Nieman, Gregg W. Stone, Patrick W. Serruys, Gabriel P. Krestin, Pim J. de Feyter
Journal: JACC. Cardiovascular imaging (2012)
Three-Phase Bone Scan Reveals Epididymo-Orchitis
Authors: D S SCHAUWECKER
Journal: Clinical Nuclear Medicine (1989)

A 14 year-old, previously healthy, white male presented with diffuse pain In the right hip area. A 3-phase bone scan was done to rule out osteomyelitis or other abnormalities of the right hip. Blood flow imaging showed increased vascularity in the right scrotum. Physical examination had revealed an enlarged minimally tender right testicle. He was treated for epididymo-orchitis; the pain subsided and he did well.
Proteolytic activity of NS3 serine proteinase of hepatitis C virus efficiently expressed inescherichia coli
Authors: Ikuo Shoji, Tetsuro Suzuki, Shinya Chieda, Mitsuru Sato, Takashi Harada, Tsutomu Chiba, Yoshiharu Matsuura, Tatsuo Miyamura
Journal: Hepatology (1995)

The serine proteinase of hepatitis C virus (HCV) non-structural protein NS3 was efficiently expressed in an active form as a fused protein with oligohistidine in Escherichia coli. The recombinant fusion protein was purified to near homogeneity by affinity chromatography on a metal chelation column. Trans-cleavage activity of this protein was investigated by using the substrate NS5 protein expressed in insect cells. The purified serine proteinase trans-cleaved the partially purified NS5 protein. In contrast, the NS3 proteins with mutations at the proposed catalytic site, Ser1165 or His1083, lost the trans-cleavage activity. Analysis of the authentic enzyme and variants with site-directed mutations provides a useful tool for understanding the structure-function relationship of the NS3 serine proteinase. We then developed an in vivo trans-cleavage assay system by coexpression of the NS3 proteinase and the NS5 substrate in E coli, and examined the effect of known inhibitors of serine proteinase. Inhibition of its proteolytic activity by N-p-tosyl-L-lysine chloromethyl ketone (TLCK) was observed, but only at high concentrations. The in vitro and in vivo trans-cleavage assays for NS3 serine proteinase will facilitate efficient testing for inhibitors of the replication of HCV and specific treatment for hepatitis C.
Preclinical assessment of simultaneous targeting of epidermal growth factor receptor (ErbB1) and ErbB2 as a strategy for cholangiocarcinoma therapy
Authors: Zichen Zhang, Regina A. Oyesanya, Deanna J. W. Campbell, Jorge A. Almenara, Jennifer L. DeWitt, Alphonse E. Sirica
Journal: Hepatology (2010)

Overexpression of epidermal growth factor receptor (ErbB1) and/or ErbB2 has been implicated in the pathogenesis of cholangiocarcinoma, suggesting that combined ErbB1/ErbB2 targeting might serve as a target-based therapeutic strategy for this highly lethal cancer. To test this strategy, we investigated targeting with the ErbB1 inhibitor tryphostin AG1517 and the ErbB2 inhibitor tryphostin AG879, in combination and alone, as well as with the dual ErbB1/ErbB2 inhibitor lapatinib, to assess the effectiveness of simultaneous targeting of ErbB1 and ErbB2 signaling over single inhibitor treatments in suppressing cholangiocarcinoma cell growth in vitro and the therapeutic efficacy of lapatinib in vivo. Our in vitro studies were carried out using rat (BDEneu and C611B) and human (HuCCT1 and TFK1) cholangiocarcinoma cell lines. The efficacy of lapatinib to significantly suppress liver tumor growth was tested in an orthotopic, syngeneic rat model of intrahepatic cholangiocarcinoma progression. Our results demonstrated that simultaneous targeting of ErbB1 and ErbB2 signaling was significantly more effective in suppressing the in vitro growth of both rat and human cholangiocarcinoma cells than individual receptor targeting. Lapatinib was an even more potent inhibitor of cholangiocarcinoma cell growth and inducer of apoptosis than either tryphostin when tested in vitro against these respective cholangiocarcinoma cell lines, regardless of differences in their levels of ErbB1 or ErbB2 protein expression and/or mechanism of activation. Lapatinib treatment also produced a significant suppression of intrahepatic cholangiocarcinoma growth when administered early to rats, but was without effect in inhibiting liver tumor growth in rats with more advanced tumors. Our findings suggest that simultaneous targeting of ErbB1 and ErbB2 could be a potentially selective strategy for cholangiocarcinoma therapy, but is likely to be ineffective by itself against advanced cancer.
Polyamines in intestinal and pancreatic adaptation.
Authors: G D Luk, P Yang
Journal: Gut (1987)

The intestinal mucosa is a rapidly proliferative tissue, with a highly dynamic cell population. Its total cellular mass is well controlled and can adapt, with hypo- or hyperplasia, to a wide variety of stimuli. Luminal nutrients, hormonal factors, and pancreatic and biliary secretions have all been implicated in the regulation of intestinal mucosal adaptation. Similarly, the same factors appear essential for the maintenance of exocrine pancreatic structure and function. The polyamines (putrescine, spermidine, and spermine) and the key enzyme controlling their synthesis (ornithine decarboxylase, ODC) are important for many cell growth processes, and may play important roles in intestinal and pancreatic adaptation. During intestinal adaptation in response to jejunectomy, lactation and pancreatico-biliary diversion (PBD), intestinal contents of ODC and polyamines are increased, paralleling increases in mucosal proliferative indices and DNA synthesis. With administration of the specific inhibitor of ODC (difluoromethylornithine, DFMO) the increases in ODC and polyamines are suppressed, and intestinal adaptation is abrogated. In pancreatic hyperplasia induced by caerulein, pancreatic polyamines are increased. With DFMO administration, caerulein-induced increases in pancreatic DNA synthesis were inhibited and pancreatic hypertrophy was partially suppressed. PBD-induced pancreatic hypertrophy, however, was not affected by DFMO. Thus, the role of polyamines in the adaptation of the pancreas, with a relatively quiescent proliferative status, is as yet undefined. It seems clear, however, that the induction of ODC and the resultant increase in polyamine biosynthesis are critical for the normal growth and especially for adaptive hyperplasia of the intestinal mucosa.
Printing the "B.M.J."
Authors: J. Furlong
Journal: BMJ (1959)

<h3>Background</h3> Despite the decline in the incidence of cervical cancer in Australia as a result of population screening, a substantial proportion of women in NSW screen less regularly than the recommended two-yearly interval or do not screen. With higher rates of cervical cancer in unscreened and underscreened women, and despite the introduction of the human papillomavirus vaccine, there remains a need to continue to remind women to screen. The mass media has been shown to be effective at improving participation in cervical screening. A 2007 television advertising campaign to promote cervical screening in New South Wales (NSW) was examined. <h3>Methods</h3> Data from the NSW Papanicolaou (Pap) Test Register were used to compare weekly numbers of Pap tests for NSW overall and in metropolitan local government areas with low screening rates by age group and by time since the last Pap test. Time series regression analysis incorporating seasonal effects was used to estimate the strength of the association between screening and the media campaign. <h3>Results</h3> Overall during the advertising campaign, 15% more screens (16 700) occurred than expected for 2007 without the advertising campaign. Increases were evident among unscreened and underscreened women, with little overscreening occurring. Women living in low screening areas also showed a significant increase in mean weekly screens of 21% (388) over that expected in the absence of the media campaign. <h3>Conclusions</h3> Despite the ecological nature of this study, the mass media campaign appears to have been successful in increasing screening in unscreened and underscreened women in NSW.
Relationship of Liver Disease Stage and Antiviral Therapy With Liver-Related Events and Death in Adults Coinfected With HIV/HCV
Authors: Berkeley N. Limketkai, Shruti H. Mehta, Catherine G. Sutcliffe, Yvonne M. Higgins, Michael S. Torbenson, Sherilyn C. Brinkley, Richard D. Moore, David L. Thomas, Mark S. Sulkowski
Journal: JAMA (2012)

<h3>Context</h3>Human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV) disease progression; however, the effect of liver disease stage and antiviral therapy on the risk of clinical outcomes is incompletely understood.<h3>Objective</h3>To determine the incidence of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), or death according to baseline hepatic fibrosis and antiviral treatment for HIV/HCV coinfected individuals.<h3>Design, Setting, and Participants</h3>Prospective cohort of 638 coinfected adults (80% black, 66% men) receiving care at the Johns Hopkins HIV clinic and receiving a liver biopsy and who were prospectively monitored for clinical events between July 1993 and August 2011 (median follow-up, 5.82 years; interquartile range, 3.42-8.85 years). Histological specimens were scored for hepatic fibrosis stage according to the METAVIR scoring system.<h3>Main Outcome Measure</h3>Incidence of composite outcome of ESLD, HCC, or death.<h3>Results</h3>Patients experienced a graded increased risk in incidence of clinical outcomes based on baseline hepatic fibrosis stage (classification range, F0-F4): F0, 23.63 (95% CI, 16.80-33.24); F1, 36.33 (95% CI, 28.03-47.10); F2, 53.40 (95% CI, 33.65-84.76); F3, 56.14 (95% CI, 31.09-101.38); and F4, 79.43 (95% CI, 55.86-112.95) per 1000 person-years (P &lt; .001). In multivariable negative binomial regression, fibrosis stages F2 through F4 and antiretroviral therapy were independently associated with composite ESLD, HCC, or all-cause mortality after adjustment for demographic characteristics, injection drug use, and CD4 cell count. Compared with F0, the incidence rate ratio (RR) for F2 was 2.31 (95% CI, 1.23-4.34; P = .009); F3, 3.18 (95% CI, 1.47-6.88; P = .003); and F4, 3.57 (95% CI, 2.06-6.19; P &lt; .001). Human immunodeficiency virus treatment was associated with fewer clinical events (incidence RR, 0.27; 95% CI, 0.19-0.38; P &lt; .001). For the 226 patients who underwent HCV treatment, the incidence of clinical events did not significantly differ between treatment nonresponders and untreated patients (incidence RR, 1.27; 95% CI, 0.86-1.86; P = .23). In contrast, no events were observed in the 51 patients with sustained virologic response (n = 36) and relapse (n = 15), including 19 with significant fibrosis.<h3>Conclusion</h3>In this cohort of patients with HIV/HCV coinfection, hepatic fibrosis stage was independently associated with a composite outcome of ESLD, HCC, or death.
Exploiting liver immunity for the prevention of hepatic metastases
Authors: Licia Rivoltini, Vincenzo Mazzaferro
Journal: Journal of Hepatology (2010)

Over the last decade immunotherapy has progressively gained a significant clinical interest for cancer treatment. The actual benefit of active immunotherapy, namely cancer vaccines, has been repeatedly claimed as effective in several settings and prompted prospective investigations (phase III clinical trials) currently ongoing in patients with prostate carcinoma, melanoma, and lung cancer, while the first vaccine for the treatment of metastatic prostate carcinoma has been recently approved by the FDA [1,2]. Adoptive immunotherapy, based on the administration of antibodies (Ab) targeting tumor receptors or molecules expressed in the microenvironment, has also entered clinical practice in several cancers such as breast carcinoma, colorectal cancer, and haematological tumors [3], whereas adoptive transfer of ex vivo activated tumor-specific T cells has shown dramatic efficacy in metastatic melanoma [4], a known benchmark-tumor for immune manipulations both in animal and human models. Ab-therapy of cancer was initially conceived to directly eliminate tumor cells by interfering with the activity of either receptors involved in cancer cell proliferation (e.g. members of the HER family) or molecules regulating tumor blood supply (such in the case of anti-VEGF Ab) [5]. However, the clinical efficacy of broadly used Ab was subsequently found to rely, at least in part, on the contribution of the immune system through the activation of antibody-dependent cell cytotoxicity (ADCC) mediated by cellular components of innate immunity [5,6]. NK cells, monocytes, macrophages, and granulocytes can indeed bind to Ab thanks to the expression of specific receptors for the invariant portion of this molecule (the so called Fc portion) and be recruited to attack target cells, hence contributing to the therapeutic potential of Abbased therapies. Evidence proving such mechanism has been collected in preclinical studies, showing that anti-tumor antibodies, like trastuzumab, have reduced activity when administered in FcR knock-out mice or used in a FcR-binding defective form. Similarly in clinical setting, breast cancer trials have reported immune infiltrate in cancer lesions of Ab-treated patients, and better efficacy in subjects expressing defined FcR genotypes [6]. More recently, the anti-tumor activity of such strategy has been also potentiated through bi-specific engineered single-chain Ab designed to tether cytotoxic T lymphocytes to cancer cells, an
PWE-116 Liver Stiffness Measurement Predicts Response to Anti-Viral Treatment in Patients with Chronic Hepatitis C Genotype 3
Authors: L Christian, A Nkhoma, A Price, M Schmid, C Miller, K Baxter, M Bassendine, S Mcpherson
Journal: Gut (2013)

<h3>Introduction</h3> Chronic hepatitis C virus infection (HCV) is a common cause of cirrhosis and end-stage liver disease. Pegylated interferon (PEG-IFN) and ribavarin (RBV) is currently the treatment of choice for genotype 3 (G3) HCV resulting in a sustained virological response (SVR) in 70–80%. Advanced fibrosis is known to be associated with failure of antiviral therapy. Increasingly, liver stiffness measurement (LSM) is being used to non-invasively assess fibrosis. However, it is not known whether LSM predicts response to antiviral therapy and whether there are predictive cut-offs. Our aim was to assess whether baseline LSM can predict SVR in HCV G3 patients treated with PEG-IFN+RBV. <h3>Methods</h3> Retrospective review of outcomes in naive patients with HCV G3 treated with PEG-IFN+RBV in our clinic from Jan 2007 to Oct 2011. Post transplant and co-infected patients were excluded. Patients with a valid LSM within 1 year of starting treatment who completed &gt; 12wks and recorded outcome of treatment were included in the LSM analysis. <h3>Results</h3> 144 patients (mean age 40±10 years, 56% male, 16% cirrhotic, and 42% high viral load) received PEG-IFN+RBV for HCV in the study period. 92% completed &gt; 12 wks treatment. 92 (64%) of patients had a valid LSM (median 6.5kPa; 3.5kPa to 39.1kPa). 24% had a LSM &gt; 10.6kPa consistent with advanced fibrosis. The overall SVR rate was 68%. 11% were lost to follow up and the outcome unknown. LSM was significantly associated with SVR (p = 0.001). The AUROC for LSM in predicting treatment response was 0.74 (95% CI 0.58–0.90). The optimum cut-off to predict non-SVR was 10.6kPa (69% sensitivity, 85% specificity). 90% with LSM ≤ 10.6kPa achieved SVR versus 47% with LSM &gt; 10.6kPa (p &lt; 0.001). All patients with low viral load (&lt; 600,000 IU/ML) and LSM &lt; 10.6 kPa who had &gt; 12 wks treatment achieved SVR (n = 33). <h3>Conclusion</h3> Fibrosis assessed non-invasively with LSM can help predict response to antiviral therapy in patients with HCV G3. LSM (&gt; or &lt; 10.6kPa) could be factored into treatment algorithms to determine the optimum treatment course lengths. <h3>Disclosure of Interest</h3> None Declared.
SKIN-GRAFTING WITHOUT DRESSINGS
Authors: JOSEPH WIENER
Journal: JAMA (1913)

Whenever we have a long list of drugs for a certain disease, not one of them is likely to be a specific. So in our surgery, whenever a large number of procedures are devised for any one lesion, the chances are that none of them "just fills the bill." So many different dressings to be used after skin-grafting have been suggested that we are forced to conclude that none of them is ideal. And yet I believe we have an ideal dressing for skingrafts, and that is no dressing at all. In January, 1907, I was asked to see a patient with extensive osteomyelitis of tibia and fibula following a crush wound. There had been extensive sloughing of the muscles and skin of the leg, so that, at a consultation of surgeons at the Long Island College Hospital, an amputation had been decided on. Although there had been a profuse
Predictive value of plasma human chorionic gonadotrophin beta subunit in diagnosing ectopic pregnancy after in vitro fertilisation and embryo transfer.
Authors: S H Okamoto, D L Healy, L M Morrow, P A Rogers, A O Trounson, E C Wood
Journal: BMJ (1987)

A study was conducted aimed at establishing a range of plasma concentrations of the beta subunit of human chorionic gonadotrophin that might predict ectopic pregnancy after in vitro fertilisation and embryo transfer. From May 1984 to February 1986, 161 consecutive pregnancies at the Monash University in vitro fertilisation unit were analysed by determining plasma beta human chorionic gonadotrophin concentrations between two and 10 weeks after oocyte collection. Eighty eight ongoing singleton pregnancies, 25 multiple pregnancies, 27 first trimester spontaneous abortions, 12 anembryonic pregnancies, and nine ectopic pregnancies resulted from these conception cycles. When compared with values for ongoing singleton pregnancies two weeks after oocyte collection plasma beta human chorionic gonadotrophin concentrations in ectopic pregnancies were significantly lower (p less than 0.05; Wilcoxon rank sum test). Two weeks after oocyte collection all plasma beta human chorionic gonadotrophin concentrations in the set of ectopic pregnancies were below 30.6 IU/l, which corresponded to the lower quartile (25th percentile) of beta human chorionic gonadotrophin concentrations in ongoing singleton pregnancies. The beta human chorionic gonadotrophin concentration corresponding to the lower quartile of ongoing singleton pregnancies at each week of gestation was used to derive the predictive value of various statistics in detecting ectopic pregnancy in patients after in vitro fertilisation. The sensitivity, specificity, predictive value of a positive result, predictive value of a negative result, and efficiency of a single plasma beta human chorionic gonadotrophin concentration in predicting ectopic pregnancy were 100%, 68.1%, 16.7%, 100%, and 70%, respectively, two weeks after oocyte collection. These results suggest that a single determination of the plasma beta human chorionic gonadotrophin concentration beginning 14 days after oocyte collection is clinically useful in predicting the outcome of pregnancy achieved by in vitro fertilisation. Ectopic pregnancy after in vitro fertilisation is more likely when beta human chorionic gonadotrophin concentration is below the lower quartile of values in ongoing singleton pregnancies achieved by the technique.
KSHV strains: the origins and global spread of the virus
Authors: Gary S. Hayward
Journal: Seminars in Cancer Biology (1999)

Nucleotide sequence analysis at five distinct loci across the 140, 000 bp genomes of more than 60 KSHV samples from KS and PEL tumors from North America, Africa, the Middle East, Asia and the Pacific revealed that they cluster into four major subtypes (A, B, C and D) that have close associations with the geographic and ethnic background of the patients. In particular, the ORF-K1 protein subtypes encoded at the extreme LHS of the genome display up to 30% amino acid variability resulting from 85% non-synonymous nucleotide substitution rates. In addition, two alternative highly diverged forms of the complex spliced ORF-K15 gene (P or M) map at the extreme RHS of the genome and are essentially unlinked to the ORF-K1 genotypes. We conclude that: (1) KSHV is an ancient human virus with several major subtypes that reflect the migrationary divergence of modern human populations over the past 35,000-60,000 years; (2) the novel immunoglobulin receptor-like signal transducing protein ORF-K1 is subject to unusually strong biological selective pressures; and (3) a minority of KSHV genomes have undergone recombination events with a related virus producing two different alleles of the ORF-K15 latency membrane protein.