tbuckley/cabot-search huggingface dataset:
Risk of Major Nonemergent Inpatient General Surgical Procedures in Patients on Long-term Dialysis
Authors: Csaba Gajdos, Mary T. Hawn, Deidre Kile, Thomas N. Robinson, William G. Henderson
Journal: JAMA Surgery (2012)

Patients on long-term dialysis undergoing major nonemergent general surgical procedures are thought to have high rates of postoperative complications and death.Retrospective cohort study.Academic and private hospitals.The American College of Surgeons National Surgical Quality Improvement Program database was used to select dialysis and nondialysis patients who had undergone nonemergent major general surgical procedures between 2005 and 2008. Multivariable logistic regression analysis was used to examine the effect of dialysis on 30-day surgical outcomes adjusted for age, race, sex, work relative value units, American Society of Anesthesiologists class, and recent operations (within the past 30 days).Patient morbidity, mortality, and failure-to-rescue rates.Dialysis patients undergoing major nonemergent general surgical procedures were significantly more likely to develop pneumonia, unplanned intubation, ventilator dependence, and need for a reoperation within 30 days from the index procedure. Dialysis patients also had a higher risk of vascular complications and postoperative death. Older dialysis patients (aged ≥ 65 years) had a significantly higher postoperative mortality rate compared with their younger counterparts. Dialysis patients were significantly more likely to die after any complication occurred, and mortality rates were especially high following stroke, myocardial infarction, and reintubation. Abnormalities in potentially modifiable preoperative variables (blood urea nitrogen level, albumin level, and hematocrit) did not increase the risk of postoperative complications or death in dialysis patients compared with nondialysis patients.Dialysis patients undergoing nonemergent general surgery have significantly elevated risks of postoperative complications and death, particularly if they are aged 65 years or older.
Increasing Prevalence of Multidrug-Resistant<i>Streptococcus pneumoniae</i>in the United States
Authors: Cynthia G. Whitney, Monica M. Farley, James Hadler, Lee H. Harrison, Catherine Lexau, Arthur Reingold, Lewis Lefkowitz, Paul R. Cieslak, Martin Cetron, Elizabeth R. Zell, James H. Jorgensen, Anne Schuchat
Journal: New England Journal of Medicine (2000)

The emergence of drug-resistant strains of bacteria has complicated treatment decisions and may lead to treatment failures.We examined data on invasive pneumococcal disease in patients identified from 1995 to 1998 in the Active Bacterial Core Surveillance program of the Centers for Disease Control and Prevention. Pneumococci that had a high level of resistance or had intermediate resistance according to the definitions of the National Committee for Clinical Laboratory Standards were defined as "resistant" for this analysis.During 1998, 4013 cases of invasive Streptococcus pneumoniae disease were reported (23 cases per 100,000 population); isolates were available for 3475 (87 percent). Overall, 24 percent of isolates from 1998 were resistant to penicillin. The proportion of isolates that were resistant to penicillin was highest in Georgia (33 percent) and Tennessee (35 percent), in children under five years of age (32 percent, vs. 21 percent for persons five or more years of age), and in whites (26 percent, vs. 22 percent for blacks). Penicillin-resistant isolates were more likely than susceptible isolates to have a high level of resistance to other antimicrobial agents. Serotypes included in the 7-valent conjugate and 23-valent pneumococcal polysaccharide vaccines accounted for 78 percent and 88 percent of penicillin-resistant strains, respectively. Between 1995 and 1998 (during which period 12,045 isolates were collected), the proportion of isolates that were resistant to three or more classes of drugs increased from 9 percent to 14 percent; there also were increases in the proportions of isolates that were resistant to penicillin (from 21 percent to 25 percent), cefotaxime (from 10 percent to 15 percent), meropenem (from 10 percent to 16 percent), erythromycin (from 11 percent to 16 percent), and trimethoprim-sulfamethoxazole (from 25 percent to 29 percent). The increases in the frequency of resistance to other antimicrobial agents occurred exclusively among penicillin-resistant isolates.Multidrug-resistant pneumococci are common and are increasing. Because a limited number of serotypes account for most infections with drug-resistant strains, the new conjugate vaccines offer protection against most drug-resistant strains of S. pneumoniae.
Faecal pH and colon cancer.
Authors: A R Walker, B F Walker
Journal: Gut (1992)

<h3>Abstract</h3> Importin-4 is the primary nuclear import receptor of core histones H3 and H4. Importin-4 binds the H3-H4 dimer and histone-chaperone ASF1 prior to nuclear import, but available structures of Importin-4·histone tail complexes do not explain how Importin-4 recognizes the biologically relevant heterotrimeric H3-H4·ASF1 cargo. Our 3.5 Å Importin-4·H3-H4·ASF1 cryo-electron microscopy structure revealed interactions with H3-H4·ASF1 different those suggested by previous Importin-H3 tail peptide structures. The N-terminal half of Importin-4 clamps the globular histone domain and the H3 αN helix while its C-terminal half binds the H3 N-terminal tail weakly, with negligible tail contribution to binding energy; ASF1 binds H3-H4 without contacting Importin-4. Together, ASF1 and Importin-4 shield nucleosomal interfaces of H3-H4 to chaperone and import it into the nucleus, where Importin-4 undergoes large conformational changes as RanGTP binds to release H3-H4·ASF1. This work explains the mechanisms of nuclear import of full-length H3-H4.
Perioperative Chemotherapy versus Surgery Alone for Resectable Gastroesophageal Cancer
Authors: David Cunningham, William H. Allum, Sally P. Stenning, Jeremy N. Thompson, Cornelis J.H. Van de Velde, Marianne Nicolson, J. Howard Scarffe, Fiona J. Lofts, Stephen J. Falk, Timothy J. Iveson, David B. Smith, Ruth E. Langley, Monica Verma, Simon Weeden, Yu Jo Chua
Journal: New England Journal of Medicine (2006)

A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer.
Stem cell transplantation for inflammatory bowel disease: practical and ethical issues
Authors: C J HAWKEY
Journal: Gut (2000)

Stem cell transplantation for inflammatory bowel disease: practical and ethical issues2][3][4][5][6][7] Recent case reports have raised the possibility that indications might be extended to inflammatory bowel disease. 8 9However, this would raise practical and ethical issues not encountered in other conditions.Inflammatory bowel disease activity involves a delicate and unpredictable balance between tolerance and immune reactivity to luminal factors that makes the outcome of stem cell transplantation diYcult to predict.Ethically, stem cell transplantation is more acceptable in some cases of systemic sclerosis where life expectancy is reduced or in multiple sclerosis where, additionally, there are few alternative eVective treatments.Neither of these principles apply to inflammatory bowel disease.
Topotecan Central Nervous System Penetration Is Altered by a Tyrosine Kinase Inhibitor
Authors: Yanli Zhuang, Charles H. Fraga, K. Elaine Hubbard, Nikolaus Hagedorn, John C. Panetta, Christopher M. Waters, Clinton F. Stewart
Journal: Cancer Research (2006)

A potential strategy to increase the efficacy of topotecan to treat central nervous system (CNS) malignancies is modulation of the activity of ATP-binding cassette (ABC) transporters at the blood-brain and blood-cerebrospinal fluid barriers to enhance topotecan CNS penetration. This study focused on topotecan penetration into the brain extracellular fluid (ECF) and ventricular cerebrospinal fluid (CSF) in a mouse model and the effect of modulation of ABC transporters at the blood-brain and blood-cerebrospinal fluid barriers by a tyrosine kinase inhibitor (gefitinib). After 4 and 8 mg/kg topotecan i.v., the brain ECF to plasma AUC ratio of unbound topotecan lactone was 0.21 +/- 0.04 and 0.61 +/- 0.16, respectively; the ventricular CSF to plasma AUC ratio was 1.18 +/- 0.10 and 1.30 +/- 0.13, respectively. To study the effect of gefitinib on topotecan CNS penetration, 200 mg/kg gefitinib was administered orally 1 hour before 4 mg/kg topotecan i.v. The brain ECF to plasma AUC ratio of unbound topotecan lactone increased by 1.6-fold to 0.35 +/- 0.04, which was significantly different from the ratio without gefitinib (P < 0.05). The ventricular CSF to plasma AUC ratio significantly decreased to 0.98 +/- 0.05 (P < 0.05). Breast cancer resistance protein 1 (Bcrp1), an efficient topotecan transporter, was detected at the apical aspect of the choroid plexus in FVB mice. In conclusion, topotecan brain ECF penetration was lower compared with ventricular CSF penetration. Gefitinib increased topotecan brain ECF penetration but decreased the ventricular CSF penetration. These results are consistent with the possibility that expression of Bcrp1 and P-glycoprotein at the apical side of the choroid plexus facilitates an influx transport mechanism across the blood-cerebrospinal fluid barrier, resulting in high topotecan CSF penetration.
Heterogeneity in responses by primary adult human colonic epithelial cells to purified enterotoxin of <i>Bacteroides fragilis</i>
Authors: L Sanfilippo, T J Baldwin, M G Menozzi, S P Borriello, Y R Mahida
Journal: Gut (1998)

Background —Enterotoxigenic strains of Bacteroides fragilis (ETBF) have been implicated in diarrhoeal illness in livestock and children, but their role in adult human colonic disease is unknown. Aims —To investigate responses by primary adult human colonic epithelial cells to purified B fragilis toxin (BFT). Methods —BFT was purified from culture supernatant of a highly toxigenic strain of ETBF. Morphological changes to primary colonic epithelial cells, in response to purified BFT, were studied in organ culture of colonic biopsy specimens from 15 adults. Results —BFT induced epithelial cell cytotoxicity in colonic biopsy specimens from 12/15 subjects. The BFT induced morphological changes were characterised by epithelial cell rounding, separation from adjacent cells, and detachment from the basement membrane. In severely affected specimens, almost all the epithelial cells were affected. There was heterogeneity between subjects in the rate at which BFT induced epithelial cell cytotoxicity occurred. Furthermore, in colonic biopsy specimens from three subjects, exposure to BFT did not induce any significant morphological changes to epithelial cells. Conclusion —BFT is capable of inducing cytotoxicity in primary adult human colonic epithelial cells. Such an effect of ETBF derived BFT on epithelial cells in the colon in vivo would be expected to lead to mucosal inflammation and diarrhoea. Heterogeneity in responses by primary colonocytes probably reflects the outcome of host-BFT interactions. Such interactions in vivo could determine the occurrence of colonic disease in some individuals but not others.
Coding sequences of the tal-1 gene are disrupted by chromosome translocation in human T cell leukemia.
Authors: Q Chen, C Y Yang, J T Tsan, Y Xia, A H Ragab, S C Peiper, A Carroll, R Baer
Journal: The Journal of Experimental Medicine (1990)

The tal-1 proto-oncogene encodes a helix-loop-helix DNA-binding protein that has been implicated in the formation of T cell acute lymphoblastic leukemia (T-ALL). Patients with T-ALL harbor structural rearrangements of tal-1 that result from either local DNA deletion or t(1;14)(p34;q11) chromosome translocation. By analyzing t(1;14)(p34;q11) chromosomes from a series of patients, we have now identified a discrete region of tal-1 wherein most of the translocation breakpoints occur. Moreover, mapping of tal-1 genomic DNA revealed that coding exons are situated on both sides of the t(1;14)(p34;q11) major breakpoint region. Hence, the translocated allele of tal-1 is truncated in a manner that reduces its amino acid coding potential.
Exercise-induced bronchoconstriction by ethnicity and presence of asthma in British nine year olds.
Authors: C O Jones, S Qureshi, R J Rona, S Chinn
Journal: Thorax (1996)

BACKGROUND: The prevalence of exercise-induced bronchoconstriction among British children by ethnicity has not been studied. METHODS: Peak expiratory flow rate (PEFR) was measured before and after an exercise challenge test using a cycle ergometer in 593 nine year olds from Scottish and inner city English schools. Logistic regression analysis was carried out to assess the association between changes in PEFR with exercise by reported asthma, ethnicity, and sex. RESULTS: The probability of exercise-induced bronchoconstriction was greater among the asthmatics than in either the children without asthma attacks or wheeze, or in the children with only wheeze (p &lt; 0.01). Asian children were 3.6 times more likely to have exercise-induced bronchoconstriction than white inner city children, and also were more likely to have exercise-induced bronchoconstriction than those from the other ethnic groups (p &lt; 0.01). CONCLUSION: Exercise challenge can assess the prevalence of asthma in the community and detect under-reporting of asthma in ethnic minorities.
Time-Action Profile of Zinc Human Insulin (recombinant DNA) in Young Volunteers as Compared with Zinc Porcine Insulin (Monotard)
Authors: F H J Vander Hoogen, S G Th Hulst, J Zweens
Journal: Diabetes Care (1982)

Zinc human insulin (recombinant DNA) or zinc PPI (Monotard) 20 U was injected subcutaneously to study the time-action profile in six healthy volunteers. During the test period they received a 10-g biscuit containing 3% moisture, 7% protein, 10% fat, 80% carbohydrate, and 30 ml of water every hour. The onset of action with zinc human insulin occurred earlier than with zinc PPI. Also, the intensity of the blood sugar-lowering effect was more pronounced 3 and 4 h after administration of insulin. No other statistically significant differences were detected between the two blood glucose curves. The results show that it is possible to develop a zinc human insulin formulation with a duration of the blood sugar-lowering effect equal to a zinc PPI formulation.
Incidence of Leukemia and Nonlymphatic Tumors in Mice With Glomerulosclerosis and Allied Disorders&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: John M. Yuhas, Neal K. Clapp
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Incidence of Leukemia and Nonlymphatic Tumors in Mice With Glomerulosclerosis and Allied Disorders Get access John M. Yuhas, John M. Yuhas Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neal K. Clapp Neal K. Clapp Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 2, February 1972, Pages 367–373, https://doi.org/10.1093/jnci/48.2.367 Published: 01 February 1972 Article history Received: 24 June 1971 Revision received: 01 November 1971 Accepted: 08 November 1971 Published: 01 February 1972
Predictors of Prophylactic Bilateral Salpingo-Oophorectomy Compared With Gynecologic Screening Use in <i>BRCA1/2</i> Mutation Carriers
Authors: Joanna B. Madalinska, Marc van Beurden, Eveline M.A. Bleiker, Heiddis B. Valdimarsdottir, Lottie Lubsen-Brandsma, Leon F. Massuger, Marian J.E. Mourits, Katja N. Gaarenstroom, Eleonora B.L. van Dorst, Hans van der Putten, Henk Boonstra, Neil K. Aaronson
Journal: Journal of Clinical Oncology (2007)

Women with BRCA1/2 gene mutations who have completed their childbearing are strong candidates for risk-reducing prophylactic bilateral salpingo-oophorectomy (PBSO). The aim of the current study was to identify baseline predictors of PBSO versus gynecologic screening (GS) in this group of high-risk women.Baseline questionnaires were available from 160 BRCA1/2 carriers who participated in a nationwide, longitudinal, observational study of the psychosocial consequences of prophylactic surgery versus periodic screening. Topics addressed by the questionnaire included generic quality of life, cancer-specific distress, risk perception, knowledge of ovarian cancer, and perceived pros and cons of surgery versus screening. PBSO use during the 12-month period after the first gynecologic consultation was determined on the basis of medical record data.During the 12-month follow-up period, 74% of women had undergone PBSO, and 26% opted for screening. Statistically significant multivariate predictors of PBSO included education, general health perceptions, perceived incurability of ovarian cancer, and perceived benefits of surgery.Women with lower educational levels, with poorer general health perceptions, who view ovarian cancer as an incurable disease, and who believe more strongly in the benefits of surgery are more likely to undergo PBSO. Clinicians should ensure that high-risk women are well informed about the low predictive value of GS techniques and about the lethal threat posed by ovarian cancer because of its limited curability.
Serum Soluble Mesothelin Concentrations in Malignant Pleural Mesothelioma: Relationship to Tumor Volume, Clinical Stage and Changes in Tumor Burden
Authors: Jenette Creaney, Roslyn J. Francis, Ian M. Dick, Arthur W. Musk, Bruce W. S. Robinson, Michael J. Byrne, Anna K. Nowak
Journal: Clinical Cancer Research (2010)

To examine the clinical utility of soluble mesothelin in patients with malignant pleural mesothelioma.A total of 97 patients (female: 11; male: 86) were prospectively enrolled, longitudinal serum samples collected, and mesothelin concentrations determined. Baseline mesothelin levels were analyzed relative to tumor stage, presence of metastatic disease, the positron emission tomography (PET) parameters maximum standardized uptake value, tumor volume, total glycolytic volume, and survival. Changes in mesothelin level were correlated to objective response to chemotherapy, as assessed radiologically and by PET imaging, and with patient survival.Baseline mesothelin levels greater than 5 nmol/L were a significant negative prognostic indicator (HR = 2.25; 95% CI, 1.20-4.21) and correlated with tumor stage and volume. In 55 patients who received chemotherapy, change in mesothelin correlated with radiological response (χ(2) = 11.32; P = 0.023) and change in metabolically active tumor volume (r = 0.58; P < 0.01). Median survival for patients with a reduction in mesothelin following chemotherapy (19 months) was significantly longer than for patients with increased mesothelin (5 months; P < 0.001).These findings show the potential value of changes in mesothelin levels for prognostication and monitoring of treatment response in mesothelioma.
A combination therapy for KRAS-driven lung adenocarcinomas using lipophilic bisphosphonates and rapamycin
Authors: Yifeng Xia, Yi-Liang Liu, Yonghua Xie, Wei Zhu, Francisco Guerra, Shen Shen, Narayana Yeddula, Wolfgang Fischer, William Low, Xiaoying Zhou, Yonghui Zhang, Eric Oldfield, Inder M. Verma
Journal: Science Translational Medicine (2014)

Lipophilic bisphosphonates combined with rapamycin inhibit the growth of KRAS -mutant lung adenocarcinomas in mouse models.
Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6
Authors: Jean-Charles Grivel, Yoshinori Ito, Giovanni Fagà, Fabio Santoro, Farida Shaheen, Mauro S. Malnati, Wendy Fitzgerald, Paolo Lusso, Leonid Margolis
Journal: Nature Medicine (2001)
A TNF receptor loop peptide mimic blocks RANK ligand–induced signaling, bone resorption, and bone loss
Authors: Kazuhiro Aoki, Hiroaki Saito, Cecile Itzstein, Masaji Ishiguro, Tatsuya Shibata, Roland Blanque, Anower Hussain Mian, Mariko Takahashi, Yoshifumi Suzuki, Masako Yoshimatsu, Akira Yamaguchi, Pierre Deprez, Patrick Mollat, Ramachandran Murali, Keiichi Ohya, William C. Horne, Roland Baron
Journal: Journal of Clinical Investigation (2006)

Activating receptor activator of NF-κB (RANK) and TNF receptor (TNFR) promote osteoclast differentiation. A critical ligand contact site on the TNFR is partly conserved in RANK. Surface plasmon resonance studies showed that a peptide (WP9QY) that mimics this TNFR contact site and inhibits TNF-α–induced activity bound to RANK ligand (RANKL). Changing a single residue predicted to play an important role in the interaction reduced the binding significantly. WP9QY, but not the altered control peptide, inhibited the RANKL-induced activation of RANK-dependent signaling in RAW 264.7 cells but had no effect on M-CSF–induced activation of some of the same signaling events. WP9QY but not the control peptide also prevented RANKL-induced bone resorption and osteoclastogenesis, even when TNFRs were absent or blocked. In vivo, where both RANKL and TNF-α promote osteoclastogenesis, osteoclast activity, and bone loss, WP9QY prevented the increased osteoclastogenesis and bone loss induced in mice by ovariectomy or low dietary calcium, in the latter case in both wild-type and TNFR double-knockout mice. These results suggest that a peptide that mimics a TNFR ligand contact site blocks bone resorption by interfering with recruitment and activation of osteoclasts by both RANKL and TNF.
Cell cycle progression proteins (cyclins), oncogene expression, and signal transduction during the proliferative response of human hepatocytes to hepatocyte growth factor
Authors: M J Gomez-Lechon, I Guillen, X Ponsoda, R Fabra, R Trullenque, T Nakamura, J V Castell
Journal: Hepatology (1996)

Human hepatocytes stimulated with human recombinant hepatocyte growth factor (h-rHGF) (10 ng/mL) displayed a characteristic lag period before entering into the S phase. The duration of this delay was dependent on the timing of h-rHGF addition to cultures. The highest peak of DNA synthesis was observed at 120 hours of culture when hepatocytes were stimulated with h-rHGF at 72 hours of culture. This was accompanied by an early peak of c- jun and c- fos synthesis (3 hours after addition of h- rHGF) followed by c- myc (6 hours) and increased expression of cyclins A, B, D, and E (12 hours after h-rHGF). A significant dose-dependent increase in inositol 1,4,5-P 3 was observed within 45 seconds after stimulation with the factor. This was followed by an immediate increase in the cytosolic-free calcium. Cyclic adenosine monophosphate (cAMP) levels did not change after stimulation with the factor. Tyrosine phosphorylation seems to be an early event in the course of the stimulatory effect of h-rHGF on DNA synthesis of hepatocytes; genistein, a tyrosine kinase inhibitor, impaired the stimulatory effect of h-rHGF on DNA synthesis dose dependently. On the other hand, the action of the factor was negatively regulated by protein kinase C activation, as shown by the increased stimulatory effect of h-rHGF on DNA synthesis upon inhibition of protein kinase C by H7.