tbuckley/cabot-search huggingface dataset:
Suramin Blockade of Insulinlike Growth Factor I-Stimulated Proliferation of Human Osteosarcoma Cells
Authors: M. Pollak, M. Richard
Journal: JNCI Journal of the National Cancer Institute (1990)

The polyanionic compound suramin is currently being evaluated for antineoplastic activity. On the basis of previous in vitro studies, it has been suggested that the mechanism of action of suramin may be related to its ability to attenuate the mitogenic effects of peptide growth factors, such as platelet-derived growth factor and epidermal growth factor. We recently reported that MG-63 human osteosarcoma cells are mitogenically responsive to insulinlike growth factor I (IGF-I). We now demonstrate for the first time that suramin interferes with the interaction between IGF-I and its receptor and abolishes in vitro IGF-I-stimulated proliferation of these osteosarcoma cells. The fact that cell proliferation resumes when suramin is removed indicates that this is not a cytotoxic effect. We conclude that IGF-I should be added to the list of growth factors whose bioactivity can be attenuated by suramin and that clinical studies of suramin and its analogues are indicated in IGF-I-receptor-positive malignancies such as osteogenic sarcoma. [J Natl Cancer Inst 82:1349–1352, 1990]
Pitfalls in processing home electronic spirometric data in asthma
Authors: HK Reddel, SI Ware, CM Salome, CR Jenkins, AJ Woolcock
Journal: European Respiratory Journal (1998)

Electronic spirometers offer the prospect of paperless home monitoring, but data quality is not automatically better than from conventional monitoring. The aim of this study was to determine the extent to which the quality and processing of self-recorded spirometric data from patients with asthma complied with international guidelines for spirometry. Data were from 33 subjects with poorly controlled asthma who had completed the first 9 weeks of a clinical budesonide trial. MicroMedical DiaryCard electronic spirometers were used to record three spirometric manoeuvres in twice-daily sessions. Confounding events were recorded in a paper diary. Within-session reproducibility was calculated for forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) during the first week of run-in and week 9 of budesonide treatment. Geometric means of within-session reproducibility (mean difference between highest and second-highest value from each session over a one-week period) for FEV1, FVC and PEF were 76 mL, 116 mL and 18 L x min(-1), respectively, during run-in. Times of spirometric sessions varied widely, with some overlap between morning and evening session times. Manoeuvre-induced falls in PEF and FEV1 occurred only as often as expected by chance. Nonasthma events including equipment faults and painful conditions caused changes in spirometric results. Home spirometric monitoring can be carried out with excellent reproducibility in patients with asthma. However, quality-control issues are complex and an accompanying paper diary remains essential.
T-cell receptor V? gene utilization in primary biliary cirrhosis
Authors: M J Mayo, B Combes, R N Jenkins
Journal: Hepatology (1996)

Semiquantitative reverse–transcriptase polymerase chain reaction (RT– PCR) was used to study the T–cell receptor (TCR) β–chain variable (Vβ) region gene families expressed by T cells in 28 patients with primary biliary cirrhosis (PBC), 20 normal controls, and 9 patients with other chronic inflammatory hepatic diseases. We hypothesized that activation and clonal proliferation of T cells would lead to biases in the T–cell repertoire of patients with PBC. Freshly harvested T cells from both peripheral blood and liver tissue were examined for evidence of biased Vβ utilization. Individuals varied considerably in their pattern of Vβ expression, but several significant differences were noted in the PBC group. In peripheral blood, the mean level of Vβ6.1,3 expression was greater in PBC patients than in normal controls. In the liver of PBC patients, the mean level of Vβ6.1,3 expression was even higher than in the peripheral blood, indicating intrahepatic accumulation of these T cells. The mean level of Vβ6.1,3 expression was not significantly different in the blood compared with liver in patients with other liver diseases. Expression of Vβ7 and Vβ13.1 was also significantly greater in the liver than in the blood of PBC patients, but similar trends were also seen in the control liver group. These data show that specific alterations in the TCR repertoire are present in the blood and liver of patients with PBC.
P138 SERONEGATIVE ACUTE LIVER FAILURE REPRESENTS A MACROPHAGE–T CELL ACTIVATION SYNDROME
Authors: E. Triantafyllou, O.T. Pop, R.D. Abeles, W. Khamri, L. Possamai, M. Hussain, W. Bernal, G. Auzinger, M.A. Heneghan, N. Heaton, M. Thursz, J. Wendon, A. Quaglia, Y. Ma, C.G. Antoniades
Journal: Journal of Hepatology (2014)
HIV incidence in men who have sex with men in England and Wales 2001–10: a nationwide population study
Authors: Paul J Birrell, O Noel Gill, Valerie C Delpech, Alison E Brown, Sarika Desai, Tim R Chadborn, Brian D Rice, Daniela De Angelis
Journal: The Lancet Infectious Diseases (2013)

BackgroundControl of HIV transmission could be achievable through an expansion of HIV testing of at-risk populations together with ready access and adherence to antiretroviral therapy. To examine whether increases in testing rates and antiretroviral therapy coverage correspond to the control of HIV transmission, we estimated HIV incidence in men who have sex with men (MSM) in England and Wales since 2001.MethodsA CD4-staged back-calculation model of HIV incidence was used to disentangle the competing contributions of time-varying rates of diagnosis and HIV incidence to observed HIV diagnoses. Estimated trends in time to diagnosis, incidence, and undiagnosed infection in MSM were interpreted against a backdrop of increased HIV testing rates and antiretroviral-therapy coverage over the period 2001–10.FindingsThe observed 3·7 fold expansion in HIV testing in MSM was mirrored by a decline in the estimated mean time-to-diagnosis interval from 4·0 years (95% credible interval [CrI] 3·8–4·2) in 2001 to 3·2 years (2·6–3·8) by the end of 2010. However, neither HIV incidence (2300–2500 annual infections) nor the number of undiagnosed HIV infections (7370, 95% CrI 6990–7800, in 2001, and 7690, 5460–10 580, in 2010) changed throughout the decade, despite an increase in antiretroviral uptake from 69% in 2001 to 80% in 2010.InterpretationCD4 cell counts at HIV diagnosis are fundamental to the production of robust estimates of incidence based on HIV diagnosis data. Improved frequency and targeting of HIV testing, as well as the introduction of ART at higher CD4 counts than is currently recommended, could begin a decline in HIV transmission among MSM in England and Wales.FundingUK Medical Research Council, UK Health Protection Agency.
Blinded Continuous Glucose Monitoring During Yom Kippur Fasting in Patients With Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy
Authors: Muriel Metzger, Lisa Lederhendler, Asher Corcos
Journal: Diabetes Care (2015)

Patients with type 1 diabetes (T1D) are generally discouraged from fasting (1,2,3). However, basal-bolus insulin regimens, by multiple injections or insulin pump therapy (CSII), allow distinctive delivery of basal and short-acting insulin and are theoretically compatible with short or prolonged fasting (4). Although many physicians consider that fasting is contraindicated, Jewish patients who renounce fasting often deeply regret not fully participating in the Yom Kippur holiday, which entails total 25-h fluid and food abstention. Conversely, some patients forsake medical advice and endanger themselves. Our study aimed to show that prolonged fasting can be safely attempted with appropriate preparation.

We recruited 10 male adult patients with T1D (aged 46 ± 12 years), on CSII for at least 1 year, willing to fast …
Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine.
Authors: T T MacDonald, J Spencer
Journal: The Journal of Experimental Medicine (1988)

T cells in explants of human fetal small intestine in organ culture were stimulated in situ with PWM or anti-CD3 antibody to test the hypothesis that activated T cells produce enteropathy in human small intestine. T cell activation was measured by the appearance of CD25+ cells in the lamina propria of the explants and IL-2 production into the organ culture supernatant. We have previously shown that the number of T cells in human fetal gut increased between 14 and 22 wk gestation. Accordingly, after the addition of PWM to cultured explants of fetal intestine the number of CD25+ cells in the lamina propria and the amounts of IL-2 secreted into the organ culture supernatant increased with the age of the explanted tissue. The addition of PWM also produced an age-related enteropathy, most noticeably crypt epithelial cell hyperplasia and villous atrophy, with relatively minor changes in 14-17-wk-old intestine but severe tissue damage in 18-22-wk-old fetal intestine. These enteropathic effects were also produced when mucosal T cells were activated with anti-CD3 mAb. Cyclosporin A completely inhibited the PWM-induced development of CD25+ cells and related tissue damage. These experiments show that activated T cells in human small intestine produce enteropathy. The model provides a new system with which to dissect the mechanisms of T cell-mediated intestinal damage.
Relationship between gastrin cell number, serum, antral mucosa and luminal gastrin concentration and gastric acidity in antral atrophic gastritis.
Authors: F Marotta, K Hayakawa, Y Mikami, P Morello, M Sugai, T Morita
Journal: Gut (1990)

The aim of our study was to investigate the relationship between gastrin producing cell density with antral mucosa, luminal and serum gastrin concentration in antral atrophic gastritis. Our study group consisted of 17 patients: six with mild atrophic gastritis, seven with moderate atrophic gastritis and four with severe atrophic gastritis. None of the patients had type-A atrophic gastritis but the body mucosa was affected by superficial gastritis at various extent in some. A group of 15 healthy subjects served as control. All subjects underwent gastroscopic examination with multiple bioptic sampling. Radioimmunoassay was used for gastrin determination and photomicroscopy for gastrin producing cell density assessment. Electron microscopy was used to assess the gastrin producing granule density index. Patients with moderate and severe atrophic gastritis showed a lower gastric acidity and acid output as compared to control. Serum gastrin did not show significant differences among the groups. In moderate and severe atrophic gastritis, gastrin producing cell granule density index, gastrin producing cell density and antral mucosa gastrin concentration were significantly lower when compared with control and decreased with advancing of the severity of atrophic gastritis. In atrophic gastritis, however, the latter two measurements were not correlated. In moderate and severe atrophic gastritis luminal gastrin concentration significantly increased, compared with control, after the severity of atrophic gastritis. Gastrin producing cell granule density index and luminal gastrin concentration showed a significant correlation with gastric pH. These data suggest that in antral atrophic gastritis with reduced gastric acidity, the decrement of gastrin producing cells is followed by gastrin producing cell hyperfunction with increased luminal release of gastrin.
Two Novel Routes of Transporter Associated with Antigen Processing (TAP)-independent Major Histocompatibility Complex Class I Antigen Processing
Authors: Heidi Link Snyder, Igor Bačík, Jack R. Bennink, Grainne Kearns, Timothy W. Behrens, Thomas Bächi, Marian Orlowski, Jonathan W. Yewdell
Journal: The Journal of Experimental Medicine (1997)

Jaw1 is an endoplasmic reticulum (ER) resident protein representative of a class of proteins post translationally inserted into membranes via a type II membrane anchor (cytosolic NH2 domain, lumenal COOH domain) in a translocon-independent manner. We found that Jaw1 can efficiently deliver a COOH-terminal antigenic peptide to class I molecules in transporter associated with antigen processing (TAP)-deficient cells or cells in which TAP is inactivated by the ICP47 protein. Peptide delivery mediated by Jaw1 to class I molecules was equal or better than that mediated by the adenovirus E3/19K glycoprotein signal sequence, and was sufficient to enable cytofluorographic detection of newly recruited thermostabile class I molecules at the surface of TAP-deficient cells. Deletion of the transmembrane region retargeted Jaw1 from the ER to the cytosol, and severely, although incompletely, abrogated its TAP-independent peptide carrier activity. Use of different protease inhibitors revealed the involvement of a nonproteasomal protease in the TAP-independent activity of cytosolic Jaw1. These findings demonstrate two novel TAP-independent routes of antigen processing; one based on highly efficient peptide liberation from the COOH terminus of membrane proteins in the ER, the other on delivery of a cytosolic protein to the ER by an unknown route.
Primary Familial Brain Calcification With Known Gene Mutations
Authors: Vera Tadic, Ana Westenberger, Aloysius Domingo, Daniel Alvarez-Fischer, Christine Klein, Meike Kasten
Journal: JAMA Neurology (2015)

In the past 2 years, 3 genes (SLC20A2, PDGFRB, and PDGFB) were identified as causative of primary familial brain calcification (PFBC), enabling genotype-specific phenotyping.To provide a systematic literature review on the neuroimaging and clinical phenotype of genetically confirmed PFBC and summarize known pathophysiological mechanisms, to improve and harmonize future phenotype description and reporting by addressing data gaps, and to develop uniform definitions for clinical characterization.We systematically searched the MEDLINE database among articles published from January 1, 2012, through May 31, 2014, for the 3 genes and selected 25 articles from all records (n=75) and from sources cited in the reference lists. Only genetically confirmed cases with individual clinical information were included, leaving 15 reports. Predefined categories for data extraction were different neurologic and psychiatric symptoms, imaging results, and age at onset (AAO). We also assessed availability of information to estimate possible bias.We included a total of 179 cases, 162 of which belong to 25 families. Availability of information ranged from 96.6% for ethnicity to 24.4% for AAO. All cases had calcifications on comprehensive cranial computed tomography, most frequently located in the basal ganglia (70.6%), subcortical white matter (40.8%), cerebellum (34.1%), or thalamus (28.5%). Mean (SD) AAO was 27.9 (22.3) years, and the AAO was comparable across genes (P=.77). The most frequently described signs were movement disorders, such as parkinsonism (12%) and dystonia (19%). Penetrance of the imaging phenotype was 100% compared with only 61% of the clinical phenotype. We propose a novel definition of disease status by specifying PFBC into genetic, clinical, and imaging phenotypes. Pathophysiological pathways converge on impaired phosphorus homeostasis and integrity of the blood-brain barrier.Especially in rare conditions, meta-analyses are the most suitable tool to extract reliable information on the natural course of a disease. For future analyses, we provide a minimal data set that can be used for systematic clinical and imaging data collection in PFBC and that will also improve informed counseling of patients.
CD4+ T Cell Polarization in Mice Is Modulated by Strain-specific Major Histocompatibility Complex–independent Differences within Dendritic Cells
Authors: Christophe Filippi, Stéphanie Hugues, Julie Cazareth, Valérie Julia, Nicolas Glaichenhaus, Sophie Ugolini
Journal: The Journal of Experimental Medicine (2003)

Resistance and susceptibility to Leishmania major in mice are determined by multiple genes and correlate with the preferential development of Th1 and Th2 responses, respectively. Here, we found that CD11b+ dendritic cells (DCs) prime parasite-specific CD4+ T cells in both susceptible BALB/c (H2-d) and resistant B10.D2 (H2-d) mice. However, BALB/c and B10.D2 DCs from L. major–infected mice differ in their ability to polarize naive T cells into Th1 or Th2 effector cells. This difference is cell-intrinsic, is not restricted to H2-d mice, and is observed with both parasite-specific and allospecific CD4+ T cells. Thus, strain-specific differences within CD11b+ DCs influence the ability of inbred mice to mount polarized CD4+ T cell responses.
mTOR and P70 S6 Kinase Expression in Primary Liver Neoplasms
Authors: Fikret Sahin, Rajesh Kannangai, Onikepe Adegbola, Jianzhou Wang, Gloria Su, Michael Torbenson
Journal: Clinical Cancer Research (2004)

Abstract Purpose: mTOR and P70 S6 kinase (S6K) play a key role in regulating protein translation. The role of mTOR and S6K in hepatocellular carcinoma has not been investigated, but this pathway is of particular interest because an effective inhibitor, rapamycin, is available. This study was undertaken to determine the prevalence and clinicopathological correlates of mTOR pathway activation in hepatocellular carcinoma and to determine whether rapamycin inhibits the pathway in cell culture. Experimental Design: Total and phosphorylated mTOR and S6K protein expression were studied by immunohistochemistry in hepatocellular carcinomas (n = 73), fibrolamellar carcinomas (n = 13), and hepatic adenomas (n = 15). Results were correlated with tumor growth pattern as defined by the WHO (trabecular, pseudoglandular/acinar, compact, and scirrhous), tumor size, Ki-67 proliferation index, and the modified Edmondson nuclear grade, which has a scale of 1 to 4. HepG2 and Hep3B cell lines were treated with rapamycin to see the effect on proliferation and S6K phosphorylation. Results: Increased expression of total mTOR was seen in 5% of hepatocellular carcinoma, whereas overexpression of phospho-mTOR was evident in 15% of hepatocellular carcinoma. Phospho-mTOR positivity correlated with increased expression of total S6K, which was found in 45% of cases. Total S6K overexpression was positively correlated with tumor nuclear grade, inversely with tumor size, and was unassociated with the proliferation index or WHO growth pattern. Rapamycin treatment of HepG2 and Hep3B cell lines markedly inhibited cell proliferation and reduced S6K phosphorylation in both cell lines. Conclusions: The mTOR pathway is activated in a subset of hepatocellular carcinoma. Rapamycin can inhibit proliferation of neoplastic hepatocytes in cell culture.
Efficacy of cabazitaxel in mouse models of pediatric brain tumors
Authors: Emily Girard, Sally Ditzler, Donghoon Lee, Andrew Richards, Kevin Yagle, Joshua Park, Hedieh Eslamy, Dmitri Bobilev, Patricia Vrignaud, James Olson
Journal: Neuro-Oncology (2014)

There is an unmet need in the treatment of pediatric brain tumors for chemotherapy that is efficacious, avoids damage to the developing brain, and crosses the blood-brain barrier. These experiments evaluated the efficacy of cabazitaxel in mouse models of pediatric brain tumors. The antitumor activity of cabazitaxel and docetaxel were compared in flank and orthotopic xenograft models of patient-derived atypical teratoid rhabdoid tumor (ATRT), medulloblastoma, and central nervous system primitive neuroectodermal tumor (CNS-PNET). Efficacy of cabazitaxel and docetaxel were also assessed in the Smo/Smo spontaneous mouse medulloblastoma tumor model. This study observed significant tumor growth inhibition in pediatric patient-derived flank xenograft tumor models of ATRT, medulloblastoma, and CNS-PNET after treatment with either cabazitaxel or docetaxel. Cabazitaxel, but not docetaxel, treatment resulted in sustained tumor growth inhibition in the ATRT and medulloblastoma flank xenograft models. Patient-derived orthotopic xenograft models of ATRT, medulloblastoma, and CNS-PNET showed significantly improved survival with treatment of cabazitaxel. These data support further testing of cabazitaxel as a therapy for treating human pediatric brain tumors.
Effectiveness and cost of facility-based Integrated Management of Childhood Illness (IMCI) in Tanzania
Authors: Joanna RM Armstrong Schellenberg, Taghreed Adam, Hassan Mshinda, Honorati Masanja, Gregory Kabadi, Oscar Mukasa, Theopista John, Sosthenes Charles, Rose Nathan, Katarzyna Wilczynska, Leslie Mgalula, Conrad Mbuya, Robert Mswia, Fatuma Manzi, Don de Savigny, David Schellenberg, Cesar Victora
Journal: The Lancet (2004)
Genetic Background Controls Tumor Development in <i>Pten</i>-Deficient Mice
Authors: Dan Freeman, Ralf Lesche, Nathalie Kertesz, Shungyou Wang, Gang Li, Jing Gao, Matthias Groszer, Hilda Martinez-Diaz, Nora Rozengurt, George Thomas, Xin Liu, Hong Wu
Journal: Cancer Research (2006)

Abstract PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. Germ line mutations of PTEN have been detected in three rare autosomal-dominant disorders. However, identical mutations in the PTEN gene may lead to different symptoms that have traditionally been described as different disorders, such as Cowden disease, Lhermitte-Duclos disease, and Bannayan-Zonana syndromes. This lack of genotype-phenotype correlation prompted us to directly test the possible effects of genetic background or modifier genes on PTEN-controlled tumorigenesis using genetically engineered mouse models. In this study, we generated two animal models in which either exon 5 (PtenΔ5) or promoter to exon 3 (Pten−) of the murine Pten gene were deleted and compared phenotypes associated with individual mutations on two genetic backgrounds. We found that the onset and spectrum of tumor formation depend significantly on the genetic background but less on the type of mutation generated. Our results suggest that PTEN plays a critical role in cancer development, and genetic background may influence the onset, the spectrum, and the progression of tumorigenesis caused by Pten mutation. (Cancer Res 2006; 66(13): 6492-6)
Spontaneous Aortosigmoid Fistula
Authors: Kuruganti R. Reddy
Journal: JAMA (1982)

SPONTANEOUS rupture of an infrarenal abdominal aortic aneurysm into retroperitoneum or peritoneal cavity is a catastrophic event. Erosion into adjacent duodenum or esophagus is even more lethal. There have even been rare reports of spontaneous aneurysmal rupture into inferior vena cava and fascia. The only hope for survival in any of these cases is high awareness and early recognition so that timely operative intervention can be undertaken.<sup>1</sup> Although rupture of aortic prosthetic grafts into small and large intestine<sup>2</sup>has been reported, we have now seen a case of spontaneous aortosigmoid fistula. <h3>Report of a Case</h3> A 79-year-old woman with a three-day history of dyspnea, abdominal pain, and painful swelling of her left thigh was admitted with congestive heart failure. Medical history included poorly controlled hypertension. On physical examination her temperature was 37.8 °C; BP, 150/90 mm Hg; pulse rate, 120 beats per minute; and respirations, 30/min. She had