tbuckley/cabot-search huggingface dataset:
Haemagglutinin mutations and glycosylation changes shaped the 2012/13 influenza A(H3N2) epidemic, Houston, Texas
Authors: K M Stucker, S A Schobel, R J Olsen, H L Hodges, X Lin, R A Halpin, N Fedorova, T B Stockwell, A Tovchigrechko, S R Das, D E Wentworth, J M Musser
Journal: Eurosurveillance (2015)

While the early start and higher intensity of the 2012/13 influenza A virus (IAV) epidemic was not unprecedented, it was the first IAV epidemic season since the 2009 H1N1 influenza pandemic where the H3N2 subtype predominated. We directly sequenced the genomes of 154 H3N2 clinical specimens collected throughout the epidemic to better understand the evolution of H3N2 strains and to inform the H3N2 vaccine selection process. Phylogenetic analyses indicated that multiple co-circulating clades and continual antigenic drift in the haemagglutinin (HA) of clades 5, 3A, and 3C, with the evolution of a new 3C subgroup (3C-2012/13), were the driving causes of the epidemic. Drift variants contained HA substitutions and alterations in the potential N-linked glycosylation sites of HA. Antigenic analysis demonstrated that viruses in the emerging subclade 3C.3 and subgroup 3C-2012/13 were not well inhibited by antisera generated against the 3C.1 vaccine strains used for the 2012/13 (A/Victoria/361/2011) or 2013/14 (A/Texas/50/2012) seasons. Our data support updating the H3N2 vaccine strain to a clade 3C.2 or 3C.3-like strain or a subclade that has drifted further. They also underscore the challenges in vaccine strain selection, particularly regarding HA and neuraminidase substitutions derived during laboratory passage that may alter antigenic testing accuracy.
Non-Hodgkin's lymphoma of the gastrointestinal tract: a population-based analysis of incidence, geographic distribution, clinicopathologic presentation features, and prognosis. Danish Lymphoma Study Group.
Authors: F d'Amore, H Brincker, K Grønbaek, K Thorling, M Pedersen, M K Jensen, E Andersen, N T Pedersen, L S Mortensen
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate incidence, time trends, geographic distribution, clinicopathologic presentation features, and prognostic factors for survival and relapse in gastrointestinal (GI) non-Hodgkin's lymphomas (NHLs). PATIENTS AND METHODS Over a 9-year period (1983 to 1991), 2,446 new NHL cases were recorded in a Danish population-based NHL registry (Danish Lymphoma Study Group [LYFO]). Of these, 306 (12.5%) were GI NHL (175 gastric, 109 intestinal, and 22 both sites). LYFO registry data were used for incidence rate (IR) assessment, and time-trend and geographic distribution analysis. Relative risk (RR) values for survival and relapse were identified by multivariate analysis. RESULTS The mean annual, age-standardized IRs for gastric and intestinal NHL were 0.71/10(5) and 0.48/10(5) per year, respectively. Age-specific IRs for both localizations showed an exponential increase as a function of age. Time-trend analysis for the period 1983 to 1991 showed stable IRs for both localizations. Intestinal NHL was more frequent in males (male-to-female ratio, 2.0 v 1.3), and had a higher occurrence of disseminated disease, constitutional symptoms, high-grade histology, and T-cell phenotype (10% v 2%). Gastric NHL had more low-grade cases (38% v 19%), and almost all were of the mucosa-associated lymphoid tissue (MALT) type. The cause-specific 5-year survival rate was 63% for gastric NHL and 49% for intestinal NHL. The Musshoff staging system was an excellent discriminator between truly localized (stage I and II1) and disseminated cases (stage II2 to IV), particularly for gastric NHL, for which no survival difference was found between surgically and conservatively stage localized cases. CONCLUSION (1) No increase in the incidence of GI NHL was found over a 9-year observation period; (2) nonrandom spatial distribution of new GI NHL cases was observed; (3) factors that significantly increased the risk of death in gastric cases were presence of B symptoms (RR = 3.3), clinical stage is more than II1 (RR = 3.0), age more than 72 years (RR = 2.4), and elevated serum lactate dehydrogenase (s-LDH) level (RR = 2.0); and factors that increased the risk of death in intestinal cases were presence of B symptoms (RR = 3.2), age more than 58 years (RR = 2.8), and clinical stage more than I (RR = 2.1); (4) factors that significantly increased the risk of relapse in gastric cases were male sex and no radiotherapy in primary treatment; and in intestinal cases were T-cell phenotype and no surgery in primary treatment; (5) surgical staging, as opposed to thorough noninvasive staging, did not improve staging accuracy and final outcome in localized gastric NHL.
ddAVP does not stimulate acute changes in levels of medullary trimethylamines in humans.
Authors: M J Avison, S K Van Why, N J Siegel
Journal: Journal of the American Society of Nephrology (1993)

1H nuclear magnetic resonance has been used to determine the effect of acute iv administration of the arginine vasopressin analog 1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (ddAVP; 2 micrograms) on renal medullary trimethylamine (TMA) levels in human volunteers. In subjects deprived of food and water for 15 h, urine osmolality (Uosm) was 889 +/- 47 mosmol/kg and had not changed significantly 3 h after ddAVP administration. Medullary TMA did not change significantly over 3 h after ddAVP. In a second group of subjects who were well hydrated, acute ddAVP infusion increased Uosm from 203 +/- 63 to 421 +/- 47 mosmol/kg in 3 h (P < 0.05). However, medullary TMA did not change significantly over this time period. These results indicate that ddAVP, and presumably arginine vasopressin, do not acutely influence medullary TMA levels, and they support the view that results previously reported for animal and isolated cell systems are also applicable to human physiology.
Isotope-Release Cytotoxicity Assay With the Use of Indium-111: Advantage Over Chromium-51 in Long-Term Assays2
Authors: R. H. Wiltrout, P. Frost, G. D. Cummings
Journal: JNCI Journal of the National Cancer Institute (1978)

The adaptation of indium-111-oxine (also known as 8-hydroxyquinoline) (111InOx) chelate for long-term (18–48 hr) isotope-release assays of cell-mediated cytotoxicity (CMC) and its advantages over the use of51Cr are described. Labeling of DBA/2 P815 mastocytoma cells with111InOx resulted in the incorporation of as many as a million counts per minute in 105 cells with no reduction in cell viability.111InOx labeled both mouse and human tumor cells.111InOx, like51Cr, primarily labeled cytoplasmic constituents; up to 80% of the label existed in a releasable form.111InOx was quantitatively released from labeled P815 in response to specifically sensitized C57BL/6 lymphocytes. The high labeling efficiency of111InOx offered a significant advantage over51Cr in 18-to 48-hour assays for CMC by reducing the counting error and thus making the assay more precise. Because of its higher labeling efficiency,111 InOx can be used in microcytotoxicity assays.111InOx has the added advantage of a lower spontaneous release in culture than51Cr. This feature of111InOx also makes the calculation of specific isotope release more accurate than that achieved with51Cr in long-term cytotoxic assays.
Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome
Authors: Da-Hai Yu, Manasi Gadkari, Quan Zhou, Shiyan Yu, Nan Gao, Yongtao Guan, Deborah Schady, Tony N. Roshan, Miao-Hsueh Chen, Eleonora Laritsky, Zhongqi Ge, Hui Wang, Rui Chen, Caroline Westwater, Lynn Bry, Robert A. Waterland, Chelsea Moriarty, Cindy Hwang, Alton G. Swennes, Sean R. Moore, Lanlan Shen
Journal: Genome biology (2015)

DNA methylation is an epigenetic mechanism central to development and maintenance of complex mammalian tissues, but our understanding of its role in intestinal development is limited.We use whole genome bisulfite sequencing, and find that differentiation of mouse colonic intestinal stem cells to intestinal epithelium is not associated with major changes in DNA methylation. However, we detect extensive dynamic epigenetic changes in intestinal stem cells and their progeny during the suckling period, suggesting postnatal epigenetic development in this stem cell population. We find that postnatal DNA methylation increases at 3' CpG islands (CGIs) correlate with transcriptional activation of glycosylation genes responsible for intestinal maturation. To directly test whether 3' CGI methylation regulates transcription, we conditionally disrupted two major DNA methyltransferases, Dnmt1 or Dnmt3a, in fetal and adult intestine. Deficiency of Dnmt1 causes severe intestinal abnormalities in neonates and disrupts crypt homeostasis in adults, whereas Dnmt3a loss was compatible with intestinal development. These studies reveal that 3' CGI methylation is functionally involved in the regulation of transcriptional activation in vivo, and that Dnmt1 is a critical regulator of postnatal epigenetic changes in intestinal stem cells. Finally, we show that postnatal 3' CGI methylation and associated gene activation in intestinal epithelial cells are significantly altered by germ-free conditions.Our results demonstrate that the suckling period is critical for epigenetic development of intestinal stem cells, with potential important implications for lifelong gut health, and that the gut microbiome guides and/or facilitates these postnatal epigenetic processes.
Clonal Origin of Metastasis in B16 Murine Melanoma: A Cytogenetic Study23
Authors: Funan Hu, Rui-Yu Wang, T. C. Hsu
Journal: JNCI Journal of the National Cancer Institute (1987)

Journal Article Clonal Origin of Metastasis in B16 Murine Melanoma: A Cytogenetic Study Get access Funan Hu, Funan Hu Search for other works by this author on: Oxford Academic PubMed Google Scholar Rui-Yu Wang, Rui-Yu Wang Search for other works by this author on: Oxford Academic PubMed Google Scholar T. C. Hsu T. C. Hsu Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 78, Issue 1, January 1987, Pages 155–163, https://doi.org/10.1093/jnci/78.1.155 Published: 01 January 1987 Article history Received: 18 March 1986 Accepted: 09 July 1986 Published: 01 January 1987
Phase II trial of interferon gamma and monoclonal antibody 17-1A in pancreatic cancer: biologic and clinical effects.
Authors: M A Tempero, C Sivinski, Z Steplewski, E Harvey, L Klassen, H D Kay
Journal: Journal of Clinical Oncology (1990)

Thirty patients with advanced measurable pancreatic adenocarcinoma were entered onto a phase II trial with recombinant interferon gamma (Biogen, Cambridge, MA; 10(6) U/m2 daily for 4 days) and monoclonal antibody (Mab) 17-1A (Centocor, Malvern, PA; 150 mg in autologous leukocytes on days 2, 3, and 4 following interferon infusion). The effect of a single interferon gamma treatment on natural and antibody-dependent cellular cytotoxicity (ADCC), Fc receptor occupancy by antibody, and human leukocyte antigen-DR (HLA-DR) expression on monocytes and lymphocytes was also studied. Toxicity was modest and generally limited to grade I to II fever, nausea and vomiting, and hepatotoxicity. Five patients were considered to be nonassessable for response. Of the 25 assessable patients, one objective response (complete remission for a duration of 4 months) was observed. Stable disease for 2 months or greater was noted in nine patients. The median survival for the group was 5 months. Analysis of cytotoxicity data obtained prior to treatment showed reduced natural cytotoxic activity in these patients compared with normal volunteers. A significant improvement in natural cytotoxic activity to normal levels occurred within 24 hours following the interferon gamma infusion. This was also associated with augmented antibody-dependent cellular cytotoxicity. Although HLA-DR expression was not increased on either monocytes or lymphocytes, an increased capacity of both lymphocytes and monocytes to bind Mab 17-1A was observed. In all in vitro assays of ADCC, the presence of antibody excess was associated with improved cytolytic activity. In spite of the favorable modulation of cytolytic activity and improved ability of effector cells to bind Mab, we failed to demonstrated adequate clinical efficacy in the treatment of patients with pancreatic adenocarcinoma using this dose and schedule of interferon gamma and Mab 17-1A. Future trials will focus on alternate schedules of Mab 17-1A with the hope of improving tumor antigen saturation and circulating levels of infused antibody.
Color Atlas of Cancer Mortality by Administrative and Other Classified Districts in Taiwan Area: 1968-1976.
Authors: Chen Kp, Wu Hy, Yeh Cc, Cheng Yj
Journal: Annals of Internal Medicine (1980)

This volume provides a detailed epidemiological survey of cancer mortality in Taiwan at the township level.  Cancer deaths and age-adjusted death rates by sex and cancer site are presented for 361 townships for the period 1968 to 1976.  Summaries of cancer mortality by rural or urban area and by ethnic area are also presented.  (summary in CHI)  (ANNOTATION)
Treatment of primary cutaneous B-cell lymphomas of follicle center cell origin: a clinical follow-up study of 55 patients treated with radiotherapy or polychemotherapy.
Authors: J U Rijlaarsdam, J Toonstra, O W Meijer, E M Noordijk, R Willemze
Journal: Journal of Clinical Oncology (1996)

PURPOSE Primary cutaneous follicle center cell lymphomas (PCFCCL) are a distinct group of cutaneous B-cell lymphomas with a favorable prognosis after radiotherapy (RT) or polychemotherapy (PCT). In the literature, conflicting data exist regarding the efficacy and the relapse rate of both treatment modalities. In the present study, treatment results and follow-up data of a large group of PCFCCL are evaluated. PATIENTS AND METHODS Fifty-five patients with a PCFCCL who presented with skin lesions on either the head (n = 12), the trunk (n = 35), or lower legs (n = 8), and who were initially treated with RT (40 cases) or PCT (15 cases) were studied. RESULTS RT resulted in a complete remission in all 40 cases. Eight cases relapsed and three of these patients died as a result of their lymphoma. The estimated 5-year survival was 89%. Four of eight relapses and all three lymphoma-related deaths occurred in the group of patients presenting with tumor(s) on the lower legs. Treatment with cyclophosphamide, doxorubicin vincristine, and prednisone (CHOP) or cyclophosphomide, vincristine, and prednisone (COP) resulted in a complete remission in 14 of 15 cases. All four cases treated with COP relapsed, whereas only two of 11 patients treated with CHOP had a relapse. The estimated 5-year survival rate of the PCT group was 93%. CONCLUSION Both RT and CHOP PCT are highly effective modes of treatment for PCFCCL. In localized PCFCCL, RT is the treatment of choice. In patients with multiple tumors involving anatomic nonrelated parts of the skin, CHOP rather than COP PCT is the preferred mode of treatment. PCFCCL on the lower legs, a subgroup that characteristically occur in elderly patients, have a higher relapse rate and a less favorable prognosis than PCFCCL presenting on the head or trunk.
Clinical Significance of a Positive Antinuclear Antibody Test
Authors: Gita Fatemi, Tanaz A. Kermani
Journal: JAMA (2015)

A30-year-oldwoman presented to the rheumatology clinic after experiencing 2months of fatigue and polyarthralgias of thewrists, hands, knees, and feet. She reported no joint swelling ormorning stiffness. She previously saw her primary care physicianwho prescribed celecoxib (for joint pain) and ordered antinuclear antibody (ANA) testing,whichwas positive at a value of 1:80 (Table). Shewas then referred to the rheumatology clinic. The patient reported nohistoryof fever,weight loss,photosensitivity,malar rashes, skin thickening,oral ornasalulcers, weakness, Raynaud phenomenon, sicca symptoms, chest pain, shortness of breath, or abdominalpain.Shewasnot takinganymedicationsbecause2weeksafter startingcelecoxib, her joint pain resolved and she discontinued usewithout recurrence of pain. The patient had nofamilyhistoryofautoimmunediseases.Onexamination,hervitalsigns, includingbloodpressure, were normal; and results of skin, thyroid, musculoskeletal, mucus membranes, cardiovascular,pulmonary,andneurologicexaminationswereallnormal.Additionaltestresults,which were obtained after her rheumatology visit, are presented in the Table.
Antibodies to an interfering epitope in hepatitis C virus E2 can mask vaccine‐induced neutralizing activity
Authors: Alla Kachko, Sharon E. Frey, Lev Sirota, Ranjit Ray, Frances Wells, Iryna Zubkova, Pei Zhang, Marian E. Major
Journal: Hepatology (2015)

Hepatitis C virus (HCV) neutralization occurring at the E2 region 412‐426 (EP‐I) could be enhanced when antibodies directed specifically to the E2 region 434‐446 (EP‐II) were removed from serum samples of persistently infected patients and vaccinated chimpanzees, a phenomenon of so‐called antibody interference. Here, we show that this type of interference can be observed in individuals after immunization with recombinant E1E2 proteins. One hundred twelve blinded serum samples from a phase I, placebo‐controlled, dose escalation trial using recombinant HCV E1E2 with MF59C.1 adjuvant in healthy HCV‐negative adults were tested in enzyme‐linked immunosorbent assay for binding reactivity to peptides representing the E2 regions 412‐426 (EP‐I) and 434‐446 (EP‐II). All samples were subsequently tested for neutralizing activity using cell‐culture HCV 1a(H77)/2a chimera, HCV pseudotype particles (HCVpp) H77, and HCVpp HCV‐1 after treatment to remove EP‐II‐specific antibodies or mock treatment with a control peptide. Among the 112 serum samples, we found 22 double positive (EP‐I and EP‐II), 6 EP‐II positive only, 14 EP‐I positive only, and 70 double negative. Depleting EP‐II antibodies from double‐positive serum samples increased 50% inhibitory dose (ID 50 ) neutralizing antibody titers (up to 4.9‐fold) in up to 72% of samples ( P ≤ 0.0005), contrasting with ID 50 neutralization titer increases in 2 of 70 double‐negative samples (2.9%; P &gt; 0.5). In addition, EP‐I‐specific antibody levels in serum samples showed a significant correlation with ID 50 neutralization titers when EP‐II antibodies were removed ( P &lt; 0.0003). Conclusion: These data show that antibodies to the region 434‐446 are induced during immunization of individuals with recombinant E1E2 proteins, and that these antibodies can mask effective neutralizing activity from EP‐I‐specific antibodies. Elicitation of EP‐II‐specific antibodies with interfering capacity should be avoided in producing an effective cross‐neutralizing vaccine aimed at the HCV envelope proteins.(H epatology 2015;62:1670–1682)
Frequency and clinical significance of cytogenetic abnormalities in pediatric T-lineage acute lymphoblastic leukemia: a report from the Children's Cancer Group.
Authors: N A Heerema, H N Sather, M G Sensel, P Kraft, J B Nachman, P G Steinherz, B J Lange, R S Hutchinson, G H Reaman, M E Trigg, D C Arthur, P S Gaynon, F M Uckun
Journal: Journal of Clinical Oncology (1998)

PURPOSE Nonrandom chromosomal translocations are frequently observed in pediatric patients with acute lymphoblastic leukemia (ALL). Specific translocations, such as t(4;11) and t(9;22), identify subgroups of B-lineage ALL patients who have an increased risk of treatment failure. The current study was conducted to determine the prognostic significance of chromosomal translocations in T-lineage ALL patients. MATERIALS AND METHODS The study included 169 children with newly diagnosed T-lineage ALL enrolled between 1988 and 1995 on risk-adjusted protocols of the Children's Cancer Group (CCG) who had centrally reviewed cytogenetics data. Outcome analyses used standard life-table methods. RESULTS Presenting features for the current cohort were similar to those of concurrently enrolled patients for whom cytogenetic data were not accepted on central review. The majority of patients (80.5%) were assigned to CCG protocols for high-risk ALL and 86.4% had pseudodiploid (n = 80) or normal diploid (n = 66) karyotypes; modal chromosome number was not a significant prognostic factor. Overall, 103 of 169 (61%) patients had an abnormal karyotype, including 31 with del(6q), 29 with 14q11 breakpoints, 15 with del(9p), 11 with trisomy 8, nine with 11q23 breakpoints, nine with 14q32 translocations, and eight with 7q32-q36 breakpoints. Thirteen patients had the specific 14q11 translocation t(11;14)(p13;q11) and all were classified as poor risk. Patients with any of these translocations had outcomes similar to those with normal diploid karyotypes. CONCLUSION Chromosomal abnormalities, including specific nonrandom translocations, were frequently observed in a large group of children with T-lineage ALL, but were not significant prognostic factors for this cohort. Thus, contemporary intensive treatment programs result in favorable outcomes for the majority of T-lineage ALL patients, regardless of karyotypic abnormalities, and such features do not identify patients at higher risk for relapse.
The allergy‐protective properties of <i>Acinetobacter lwoffii</i> F78 are imparted by its lipopolysaccharide
Authors: J. Debarry, A. Hanuszkiewicz, K. Stein, O. Holst, H. Heine
Journal: Allergy (2009)

To cite this article: Debarry J, Hanuszkiewicz A, Stein K, Holst O, Heine H. The allergy‐protective properties of Acinetobacter lwoffii F78 are imparted by its lipopolysaccharide. Allergy 2010; 65 : 690–697. Abstract Background: An increasing number of epidemiological studies show that exposure to farming environment during early childhood strongly influences the development of allergic reactions later in life (‘hygiene hypothesis’). Also, it had been shown that certain bacteria from this environment may have allergy‐protective properties. In the present study, we further characterized one of these bacteria, namely Acinetobacter lwoffii F78, with regard to the bacteria‐induced signaling and possible mechanisms of allergy protection. Methods: The impact of A. lwoffii F78 on human monocyte‐derived dendritic cells especially with respect to their T Helper cell polarization capacity was investigated by ELISA and real‐time PCR experiments as well as confocal microscopy. The responsible molecule for these effects was further characterized and identified using blocking experiments. Results: It was shown that A. lwoffii F78 induced a T H 1‐polarizing program in human dendritic cells which led to T H 1 differentiation. In addition, a positive influence on the TBet/GATA3 level could be detected. Blocking experiments revealed that the lipopolysaccharide (LPS) of A. lwoffii F78 was the responsible molecule promoting these effects. Conclusion: We found evidence that the allergy‐protecting effects of A. lwoffii F78 are because of the activation of a T H 1‐polarizing program in human dendritic cells, and that the LPS of A. lwoffii F78 is responsible for these beneficial effects.
Role of Clopidogrel Loading Dose in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Angioplasty
Authors: George Dangas, Roxana Mehran, Giulio Guagliumi, Adriano Caixeta, Bernhard Witzenbichler, Jiro Aoki, Jan Z. Peruga, Bruce R. Brodie, Dariusz Dudek, Ran Kornowski, LeRoy E. Rabbani, Helen Parise, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2009)