tbuckley/cabot-search huggingface dataset:
Abstract 2905: Is obesity the cause for the increasing incidence of CRC in patients under 50 years of age and can an anti-adenoma antibody identify those at risk
Authors: Allen Hwang, Daniel Elkin, David Kaplan, Fadi Antaki, Mary Ann Rambus, Bonita Leavell, Joann Naumoff, Rebecca Rodriguez, James Hatfield, Yi Xu, Pragnesh Patel, Tatwig Guirguis, Michael Lawson, Martin Tobi
Journal: Cancer Research (2010)

Abstract CRC incidence in patients &amp;lt;50 years of age has increased by 17% in the last decade predominantly rectal cancer in Whites (Siegel et al, 2009). This age group is rarely screened. We determined the rectal binding Adnab-9 antibody in patients &amp;lt;50 years and a &amp;gt;50 year control at high clinical CRC risk of cancer. Methods: Adnab-9 is an adenoma-carcinoma sequence marker. We performed Adnab-9 immunohistocemistry on colonoscopic rectal biopsies. Results: Our study found that of 25 patients age &amp;lt;50 years, 48% had rectal binding of Adnab-9 versus 21.8% in 220 patients ≥50yrs (p&amp;lt;0.01) and with BMI was confirmed as an independent risk factor by multivariate analysis. Demographics are summarized (Table) and significant differences were seen for gender, ASA intake and BMI, however female gender was equally distributed 58.3 in the positive and 61.5% in the negative group. Hematochezia tended (p=0.23) to associate with positive rectal binding (50 versus 23%) and the colonoscopic finding was more likely to reveal adenomatous tissue in the positive group (58.3 versus 23.1%, p=0.11). Older patients were significantly more likely to take ASA which may have reduced the polyp number in this group and they also have an decreased BMI (p&amp;lt;0.02). In the entire group Adnab-9 positivity correlated with BMI as a continuous variable (U=0.03; p&amp;lt;0.01). Conclusions: Adnab-9 is an independent CRC risk marker in patients &amp;lt;50 years of age suggesting that they are more prone to development of neoplasia. The mechanism appears to be that of an adenoma-carcinoma sequence. ASA may be a factor but was not an independent mitigating marker in this study. BMI is also greater in the younger group and may be the underlying cause of the observed increase in neoplasia in the young. Adnab-9 staining of sigmoidoscopic rectal biopsies may be a convenient way of identifying a high-risk population of patients &amp;lt;50 years of age for CRC surveillance in this population hithertofore not afforded screening.Parameter (n)Patients &amp;lt;50 (25)Patients &amp;gt;50 (220)Age(mean+st.deviation[SD])44.8 (5.4)62.4 (9.3)% Non-Hispanic Whites4041.4% Female Gender60 (OR 11.0, CI 4.4-27.2; p&amp;lt;0.0001)10.9Any NSAID/Statin/ASA(%)30.4/44/41.18/4.6 (less ASA-p&amp;lt;0.02)37.6/46.6/30.5Symptom %/BMI(SD)60/31.6(6.1) (BMI p&amp;lt;0.02)*42.9/28.7(5.4) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2905.
Decreased hepcidin expression in murine β-thalassemia is associated with suppression of Bmp/Smad signaling
Authors: Nermi L. Parrow, Sara Gardenghi, Pedro Ramos, Carla Casu, Robert W. Grady, Erik R. Anderson, Yatrik M. Shah, Huihui Li, Yelena Z. Ginzburg, Robert E. Fleming, Stefano Rivella
Journal: Blood (2012)
Raynaud's Phenomenon: A Common Toxicity After Combination Chemotherapy for Testicular Cancer
Authors: NICHOLAS J. VOGELZANG
Journal: Annals of Internal Medicine (1981)

Raynaud's phenomenon occurred in 22 of 60 men (37%) treated with vinblastine and bleomycin with or without cisplatin for germ cell testicular cancer. An additional six patients (10%) had symptoms suggestive of Raynaud's phenomenon. Patients with and without Raynaud's phenomenon did not differ with respect to median age; tumor histology; total doses of vinblastine, bleomycin, and cisplatin; or the frequency of vinblastine-induced neuropathy and bleomycin-induced cutaneous toxicity. Digital ischemia occurred in 21% of patients treated with only vinblastine and bleomycin, and in 41% of patients treated also with cisplatin. Cigarette smoking was commoner in patients with than in those without Raynaud's phenomenon. Hand arteriograms showed diffuse arterial narrowing and abrupt vascular cutoffs. Except for one patient with a very low titer of cold agglutinins, no patient had detectable antinuclear antibody, rheumatoid factor, cryoglobulins, or cold agglutinins. Raynaud's phenomenon is a common delayed toxicity after chemotherapy with vinblastine, bleomycin, and cisplatin in patients with germ cell neoplasms.
Helper cell-independent cytotoxic clones in man.
Authors: S L Wee, L K Chen, G Strassmann, F H Bach
Journal: The Journal of Experimental Medicine (1982)

We report here a class of helper cell-independent cytotoxic T cell (HITc) clones in man that can proliferate in response to antigenic stimulation as well as mediate cytotoxicity. HITc appear to be rare among clones derived from primary in vitro allosensitized culture, but constitute the majority of clones derived from cells sensitized to autologous Epstein-Barr virus-transformed lymphoblastoid cell lines. The implications of the derivation and function of HITc clones are discussed.
Monoclonal B‐cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B‐cell subsets
Authors: Alexander W. Hauswirth, Julia Almeida, Wendy G. Nieto, Cristina Teodosio, Arancha Rodriguez‐Caballero, Alfonso Romero, Antonio López, Paulino Fernandez‐Navarro, Tomas Vega, Martin Perez‐Andres, Peter Valent, Ulrich Jäger, Alberto Orfao
Journal: American Journal of Hematology (2012)

Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets.Little is known about the distribution of normal lymphoid cells and their subsets in the peripheral blood (PB) of subjects with monoclonal B-cell lymphocytosis (MBL). In our study, we compared the absolute number of PB lymphoid cells and their subpopulations in 95 MBL cases with normal lymphocyte counts vs. 617 age-/sex-matched non-MBL healthy subjects (controls), using highly sensitive flow cytometry. MBL cases showed significantly reduced numbers of normal circulating B-cells, at the expense of immature and naive B-cells; in addition, CD4+CD8+ double-positive T-cells and CD8+ T-cells were significantly lower and higher vs. controls, respectively. Moreover, most normal B-cell subsets were significantly decreased in PB at >1% MBL-counts, vs. "low-count" MBL cases, and lower amounts of immature/naive B-cells were detected in biclonal (particularly in cases with coexisting CLL-like- and non-CLL-like B-cell clones) vs. monoclonal MBL subjects. In summary, our results show imbalanced (reduced) absolute numbers of recently produced normal circulating B-cells (e.g., immature and naıve B-cells) in MBL, which becomes more pronounced as the MBL cell count increases.
Moderate altitude has no effect on choice reaction time in international rugby players.
Authors: R E O'Carroll, D MacLeod
Journal: British Journal of Sports Medicine (1997)

There are only a few conflicting reports on the effects of moderate altitude on cognitive factors that could affect sporting performance. An investigation of choice reaction time in international rugby players at various altitudes was therefore carried out. The results suggest that moderate altitude has no significant effect on this parameter in highly trained competitive athletes.
Effect of Non–Insulin-Dependent Diabetes Mellitus on Myocardial Insulin Responsiveness in Patients With Ischemic Heart Disease
Authors: Dinesh Jagasia, Jennifer M. Whiting, John Concato, Steven Pfau, Patrick H. McNulty
Journal: Circulation (2001)

Background —Patients with non–insulin-dependent diabetes mellitus (NIDDM) exhibit poor clinical outcomes from myocardial ischemia. This may reflect an impairment in their cardiac insulin-response system. Methods and Results —We used AV balance and intracoronary infusion techniques to compare the intrinsic cardiac responsiveness to insulin in 26 coronary disease patients with (n=13) and without (n=13) NIDDM. During fasting, NIDDM hearts demonstrated lower fractional extraction of glucose from arterial plasma than controls (1.0±0.5% versus 2.1±0.5%, P &lt;0.05) despite higher circulating insulin levels (26±5 versus 13±4 μU · mL, P &lt;0.05). This was compensated for by higher circulating glucose levels, so that net cardiac glucose uptake in the 2 groups was equivalent (5.2±1.1 versus 5.3±1.1 μmol · min). Intracoronary insulin infusion produced an ≈3-fold increase in fractional extraction and net uptake of glucose across the heart in both groups (to 3.7±0.4% and 18.3±3.5 μmol · min in NIDDM and to 5.4±0.7% and 17.7±4.3 μmol · min in controls) accompanied by an ≈30% increase in net lactate uptake, suggesting preserved insulin action on both glucose uptake and glucose oxidation in the NIDDM heart. In nondiabetics, insulin consistently increased coronary blood flow, but this effect was absent in NIDDM. Conclusions —In contrast to their peripheral tissues and coronary vasculature, the myocardium of patients with NIDDM expresses a competent insulin-response system with respect to glucose metabolism. This suggests that insulin resistance is mediated at the level of individual organs and that different mechanisms are involved in muscle and vascular tissue.
Decreased diversity of nasal microbiota and their secreted extracellular vesicles in patients with chronic rhinosinusitis based on a metagenomic analysis
Authors: E.‐B. Choi, S.‐W. Hong, D.‐K. Kim, S. G. Jeon, K.‐R. Kim, S.‐H. Cho, Y. S. Gho, Y.‐K. Jee, Y.‐K. Kim
Journal: Allergy (2014)

Abstract Background Chronic rhinosinusitis ( CRS ) is an inflammatory process in the nasal cavity and paranasal sinuses, and bacteria have been considered to be a cause. Indeed, recent evidence indicates that bacteria‐derived extracellular vesicles ( EV ) appear to be an important causative agent of inflammatory diseases. Here, we aimed to evaluate the diversity of nasal microbiota and their secreted EV in patients with CRS . Methods Nasal lavage ( NAL ) fluid samples were obtained from five patients with CRS with polyposis, three patients with CRS without polyposis, and three non‐ CRS controls. After preparation of bacteria and EV from samples using differential centrifugation, genomic DNA was extracted and 16S‐ rDNA amplicons were subjected to high‐throughput pyrosequencing on a Roche 454 GS‐FLX platform. Results Metagenomics showed that bacteria composition was positively correlated with EV composition. Samples from patients with CRS had greater bacterial abundance and lower diversity, both from bacteria and the EV portion of samples, compared with non‐ CRS samples. At each phylogenetic level, Bacteroidetes decreased while Proteobacteria increased in the CRS group at the phylum level. At the genus level, Prevotella spp. decreased in the CRS group, while Staphylococcus spp. increased from both bacteria and EV . Moreover, Staphylococcus aureus and its secreting EV compositions were higher in samples from CRS with polyps compared with CRS without polyps. Conclusions These results suggest that patients with CRS have altered nasal microbiota and decreased diversity in bacterial compositions as well as increased S. aureus abundance in those patients with polyps.
Peripheral transvenular delivery of adeno-associated viral vectors to skeletal muscle as a novel therapy for hemophilia B
Authors: Valder R. Arruda, Hansell H. Stedman, Virginia Haurigot, George Buchlis, Stefano Baila, Patricia Favaro, Yifeng Chen, Helen G. Franck, Shangzhen Zhou, J. Fraser Wright, Linda B. Couto, Haiyan Jiang, Glenn F. Pierce, Dwight A. Bellinger, Federico Mingozzi, Timothy C. Nichols, Katherine A. High
Journal: Blood (2010)
Abstract 423: Metabolomic analysis of urine from patients undergoing total body irradiation.
Authors: Evagelia C. Laiakis, Tytus D. Mak, Sebastien Anizan, Sally A. Amundson, Christopher A. Barker, Suzanne L. Wolden, David J. Brenner, Albert J. Fornace
Journal: Cancer Research (2013)

Abstract Development of biomarkers for the responses to radiation has relevance to assessment of patient course and outcome after radiation therapy, as well as to other radiologic events including accidental and terrorist. The purpose of this study was to extend the biomarker discovery to humans, as previous studies have focused on mice. Urine was collected from patients undergoing total body irradiation (TBI) at Memorial Sloan Kettering prior to bone marrow transplantation at 4-6h post irradiation (a single dose of 125cGy) and 24h (three fractions of 125cGy each). Patient diagnoses include leukemias (ALL, AML, and CML), non-hodgkins lymphoma, myelodysplastic syndrome, aplastic anemia, and essential thrombocytopenia. Global metabolomic profiling was obtained through analysis with Ultra Performance Liquid Chromatography (UPLC) coupled to time-of-flight mass spectrometry (TOFMS) (Waters). Peak alignment and deconvolution of the chromatographic data were conducted with MarkerLynx software (Waters, MA). Prior to further analysis, each sample was normalized to its respective creatinine. Ions with non-zero abundance values in at least 75% of samples in both groups were analyzed for statistical significance via the nonparametric Kolmogorov-Smirnov test for equality of probability distributions on the log-transformed dataset. Statistical significance for ions with non-zero abundance values in at least 75% of samples in only one group were analyzed categorically for presence (i.e. non-zero abundance) via the Fisher's exact test. Biomarker candidates were verified by tandem mass spectrometry (MS/MS) by comparison to pure chemicals and quantification of the markers was conducted with the triple quadrupole mass spectrometer XEVO TQ MS (Waters). Validated and quantified biomarkers include L-Octanoylcarnitine, Hypoxanthine, Trimethyl-L-Lysine, Acetyl-carnitine, Decanoylcarnitine, Pantothenic acid, Hippuric acid, Uric acid, and Xanthine, and thus contribute to the development of a human metabolomic signature following exposure to radiation, and can now be integrated with features including underlying disease status, gender, age, and outcome. Citation Format: Evagelia C. Laiakis, Tytus D. Mak, Sebastien Anizan, Sally A. Amundson, Christopher A. Barker, Suzanne L. Wolden, David J. Brenner, Albert J. Fornace. Metabolomic analysis of urine from patients undergoing total body irradiation. [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 423. doi:10.1158/1538-7445.AM2013-423
Protein kinase A-dependent phosphorylation of Dock180 at serine residue 1250 is important for glioma growth and invasion stimulated by platelet derived-growth factor receptor 
Authors: H. Feng, Y. Li, Y. Yin, W. Zhang, Y. Hou, L. Zhang, Z. Li, B. Xie, W.-Q. Gao, J. N. Sarkaria, J. J. Raizer, C. D. James, A. T. Parsa, B. Hu, S.-Y. Cheng
Journal: Neuro-Oncology (2014)

Dedicator of cytokinesis 1 (Dock1 or Dock180), a bipartite guanine nucleotide exchange factor for Rac1, plays critical roles in receptor tyrosine kinase–stimulated cancer growth and invasion. Dock180 activity is required in cell migration cancer tumorigenesis promoted by platelet derived growth factor receptor (PDGFR) and epidermal growth factor receptor. To demonstrate whether PDGFRα promotes tumor malignant behavior through protein kinase A (PKA)–dependent serine phosphorylation of Dock180, we performed cell proliferation, viability, migration, immunoprecipitation, immunoblotting, colony formation, and in vivo tumorigenesis assays using established and short-term explant cultures of glioblastoma cell lines. Stimulation of PDGFRα results in phosphorylation of Dock180 at serine residue 1250 (S1250), whereas PKA inhibitors H-89 and KT5720 oppose this phosphorylation. S1250 locates within the Rac1-binding Dock homology region 2 domain of Dock180, and its phosphorylation activates Rac1, p-Akt, and phosphorylated extracellular signal-regulated kinase 1/2, while promoting cell migration, in vitro. By expressing RNA interference (RNAi)–resistant wild-type Dock180, but not mutant Dock180 S1250L, we were able to rescue PDGFRα-associated signaling and biological activities in cultured glioblastoma multiforme (GBM) cells that had been treated with RNAi for suppression of endogenous Dock180. In addition, expression of the same RNAi-resistant Dock180 rescued an invasive phenotype of GBM cells following intracranial engraftment in immunocompromised mice. These data describe an important mechanism by which PDGFRα promotes glioma malignant phenotypes through PKA-dependent serine phosphorylation of Dock180, and the data thereby support targeting the PDGFRα-PKA-Dock180-Rac1 axis for treating GBM with molecular profiles indicating PDGFRα signaling dependency.
Periungual and subungual arteriovenous tumours
Authors: S.M. BURGE, R. BARAN, R.P.R. DAWBER, J.L. VERRET
Journal: British Journal of Dermatology (1986)

We describe the clinicopathological findings in five cases of an acquired vascular tumour involving periungual or subungual tissue. We believe that these represent acral arteriovenous tumours (cirsoid aneurysms). There are no previous reports of subungual or periungual acral arteriovenous tumours.
Luminal Bacteria Recruit CD103+ Dendritic Cells into the Intestinal Epithelium to Sample Bacterial Antigens for Presentation
Authors: Julia Farache, Idan Koren, Idan Milo, Irina Gurevich, Ki-Wook Kim, Ehud Zigmond, Glaucia C. Furtado, Sergio A. Lira, Guy Shakhar
Journal: Immunity (2013)
Abstract 1052: Refametinib (BAY 86-9766): An allosteric inhibitor of MEK1/2, potently inhibits tumor growth in patient-derived xenograft models of gastric cancer.
Authors: Huynh T. Hung, Richard Ong, Khee Chee Soo, Florian Puehler, Arne Scholz, Dominik Mumberg, Dieter Zopf, Karl Ziegelbauer
Journal: Cancer Research (2013)

Abstract Background: Gastric cancer (GC) is a prevalent and deadly disease. Because the Ras/Raf/MEK/ERK signaling cascade plays a critical role in signal transduction pathways that regulate growth factor response, angiogenesis, tumor cell proliferation, and apoptosis, blocking this signaling pathway could thus have therapeutic efficacy. This study aims to target this pathway in preclinical models of GC with refametinib (BAY 86-9766, RDEA119), an orally available, allosteric inhibitor of MEK1/2. Methods: Eight patient-derived GC xenograft models with different histotypes were treated orally with refametinib or vehicle and tumor growth was monitored using caliper measurements. Tissue sections of vehicle- or refametinib-treated xenografts were analyzed by immunohistochemistry for cell proliferation, apoptosis and microvessel area, using antibodies against p-Histone H3Ser10, cleaved PARP and CD31, respectively. Tumor lysates were analyzed by Western Blotting with antibodies for effects on marker proteins for proliferation, apoptosis and angiogenesis.Results: Refametinib demonstrated significant tumor growth inhibition ranging from 66-87% in eight GC models at a dose of 15 mg/kg/d. Refametinib inhibited cell proliferation by 2-4 fold as observed by reduced staining for p-Histone H3Ser10. Increased staining for caspase-cleaved p85 PARP by 1.5 to 9 fold was detected, indicating that refametinib induced apoptosis. Furthermore the compound significantly inhibited angiogenesis in 2 of 8 models by 3-fold compared to the vehicle-treated group as indicated by reduced CD31 staining. Reduced cell proliferation and induction of apoptosis were associated with decreased levels of p-ERK1/2, p-cdk2Thr14/Tyr15, p-p90RSKSer359/363, p-p70S6KThr421/Ser424, p-4EBP1Thr70, p-S6RSer235/236 and p-eIF4ESer209 and elevation of p-AktSer473, Bim and cleaved PARP. Conclusion: We show that single-agent refametinib has significant anti-tumor activity in patient-derived gastric cancer preclinical models. Our findings support further investigation of refametinib either in monotherapy or in combination with inhibitors of the PI3K-AKT-mTOR pathway in the treatment of GC. Citation Format: Huynh T. Hung, Richard Ong, Khee Chee Soo, Florian Puehler, Arne Scholz, Dominik Mumberg, Dieter Zopf, Karl Ziegelbauer. Refametinib (BAY 86-9766): An allosteric inhibitor of MEK1/2, potently inhibits tumor growth in patient-derived xenograft models of gastric cancer. [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 1052. doi:10.1158/1538-7445.AM2013-1052
Ivan Francis Mackinnon Buchanan
Authors: Graham Petrie
Journal: BMJ (2004)

Former general practitioner Cambridge (b Basra, Iraq, 1929; q Cambridge/Bristol 1956), died from acute hepatic failure caused by herpetic hepatitis on 9 September 2004.​2004.




Figure 1




Ivan joined a central (“university”) practice in 1969 after 10 years as a general practitioner in Weston-super-Mare. His earlier career had been interrupted by lymph node tuberculosis, which in turn made him ineligible for national service. Besides an extensive practice in the academic community and beyond, he was for some 10 years a clinical assistant at the Rosie Maternity Hospital in Cambridge, a period that fuelled his interest in obstetrics. He was also one of the early MAGPAS (Mid-Anglia General Practitioner Accident Service) doctors. He was a skilled bagpipe player. He leaves a wife, Bodil; four children; and eight grandchildren.
Truncation of the cytoplasmic domain of beta3 in a variant form of Glanzmann thrombasthenia abrogates signaling through the integrin alpha(IIb)beta3 complex.
Authors: R Wang, S J Shattil, D R Ambruso, P J Newman
Journal: Journal of Clinical Investigation (1997)

Glanzmann thrombasthenia is an inherited bleeding disorder characterized by absence or dysfunction of the platelet integrin alpha(IIb)beta3. Patient RM is a thrombasthenic variant whose platelets fail to aggregate in response to physiological agonists, despite the fact that they express abundant levels of alpha(IIb)beta3 on their surface. Binding of soluble fibrinogen or fibrinogen mimetic antibodies to RM platelets did not occur, except in the presence of ligand-induced binding site (LIBS) antibodies that transformed the RM integrin complex into an active conformation from outside the cell. Sequence analysis of PCR-amplified genomic DNA and platelet mRNA revealed a C2268T nucleotide substitution in the gene encoding the integrin beta3 subunit that resulted in an Arg724Ter mutation, producing a truncated protein containing only the first eight of the 47 amino acids normally present in the cytoplasmic domain. Functional analysis of both RM platelets and CHO cells stably expressing this truncated integrin revealed that the alpha(IIb)beta3Arg724Ter complex is able to mediate binding to immobilized fibrinogen, though downstream events, including cytoskeletally-mediated cell spreading and tyrosine phosphorylation of focal adhesion kinase, pp125FAK, fail to occur. These studies establish the importance of the membrane-distal portion of the integrin beta3 cytoplasmic domain in bidirectional transmembrane signaling in human platelets, and the role of integrin signaling in maintaining normal hemostasis in vivo.