tbuckley/cabot-search huggingface dataset:
Vaccination of Mice with Replication-Defective Human Immunodeficiency Virus Induces Cellular and Humoral Immunity and Protects against Vaccinia Virus-gag Challenge
Authors: Christopher S. Baliga, Marc van Maanen, Michael Chastain, Richard E. Sutton
Journal: Molecular Therapy (2006)

Here we describe as a potential vaccine candidate a replication-defective HIV that encodes multiple viral genes in addition to a cassette that includes both truncated cyclin T1 and an autofluorescent protein. After confirming functionality of the cyclin T1, we immunized mice intramuscularly once or twice with the replication-defective HIV vector pseudotyped with vesicular stomatitis virus (VSV) G protein (RD HIV), a plasmid encoding CMV-driven gag (gag DNA), or adenovirus gag (Ad5-gag). Capsid-specific antibody titers following RD HIV immunization were >106/ml and approximately equivalent to those induced by gag DNA and Ad5-gag. Antibodies against the autofluorescent protein and VSV G were also detected. After RD HIV immunization ELISpot assays demonstrated Gag-specific interferon-γ (IFN-γ) SFU equivalent to that of Ad5-gag and fourfold greater than that of gag DNA. HIV polymerase-specific IFN-γ SFU values were similar, and boosting increased both antibody titers and the IFN-γ response. Challenge using vaccinia virus (VV)-gag demonstrated significantly lower recoverable VV for RD HIV-immunized mice compared to controls. No significant differences were observed in vaccinated mice challenged with wild-type VV. This study demonstrates the efficacy of RD HIV in conferring HIV-specific immunity and protection in mice and suggests its potential use in humans as either a prophylactic or a therapeutic vaccine.
A phase I clinical and pharmacokinetic study of carboplatin and autologous bone marrow support.
Authors: T C Shea, M Flaherty, A Elias, J P Eder, K Antman, C Begg, L Schnipper, E Frei, W D Henner
Journal: Journal of Clinical Oncology (1989)

A series of 33 patients were treated with a four-day continuous infusion of carboplatin in a phase I study to determine the maximum-tolerated dose (MTD) of this agent when used with autologous bone marrow reinfusion. Doses were escalated from 375 to 2,400 mg/m2; autologous bone marrow reinfusion was added to the regimen at doses of 1,600 mg/m2 and above. The MTD was determined to be 2,000 mg/m2. Dose-limiting toxicity consisting of reversible hepatotoxicity, renal dysfunction, and moderate to severe ototoxicity was observed with a dose of 2,400 mg/m2. There were ten responses in 31 heavily pretreated patients, including six responses in 11 patients with recurrent ovarian cancer. Pharmacokinetic studies revealed a systemic clearance (Clss) of 4.5 L/m2/h. This value is consistent with clearances reported for carboplatin administered at lower doses and by different schedules. No evidence for saturation of systemic clearance at higher doses was observed. Carboplatin appears to be an active drug that can undergo considerable dose escalation when used in conjunction with autologous bone marrow support.
The human fetal omentum: a site of B cell generation.
Authors: N Solvason, J F Kearney
Journal: The Journal of Experimental Medicine (1992)

The fetal mouse omentum has been shown to be a source of precursors that exclusively reconstitutes Ly1+ B cells and the closely related Ly1- sister population, but not conventional B cells or T cells. We have extended these studies to compare B cell development in the human fetal omentum, liver, and spleen, and to demonstrate that the pro/pre-B cell compartment (CD24+, sIgM-) is detected in the omentum and liver but not spleen as early as 8 wk of gestation. From 8 to 12 wk of gestation, the proportions of IgM+ cells that were pre-B cells (cIgM+/sIgM-) in the omentum and liver were 53 +/- 15% and 45 +/- 13%, respectively, and IgM+ cells were not detectable in the spleen. After 12 wk, the percentage of pre-B cells was unchanged in the fetal liver (41 +/- 10%) but decreased significantly in the omentum (25 +/- 14%); pre-B cells were now detected in the spleen but at much lower percentages (2 +/- 3%) than either the omentum or liver. The nuclear enzyme, Tdt, was detected in approximately 25% of the CD24+ cells in the omentum and liver during the 8-12-wk time period, however, Tdt+ cells were not detected in the spleen. Approximately 40% of the mature B cells found in the omentum and spleen were CD5+ compared with only 20% in the liver. These results demonstrate that the fetal omentum, like the fetal liver and bone marrow, is a primary site of B cell development.
Rechallenge with EGFR-TKI after a Drug Holiday, Retrospective Study in Single Institution
Authors: M. Kodani, T. Igishi, T. Sakamoto, H. Touge, H. Izumi, S. Ito, J. Kurai, K. Yamaguchi, M. Nakamoto, E. Shimizu
Journal: Annals of Oncology (2013)
Impact of Sleep Duration on Obesity and the Glycemic Level in Patients With Type 2 Diabetes
Authors: Toshiaki Ohkuma, Hiroki Fujii, Masanori Iwase, Yohei Kikuchi, Shinako Ogata, Yasuhiro Idewaki, Hitoshi Ide, Yasufumi Doi, Yoichiro Hirakawa, Udai Nakamura, Takanari Kitazono
Journal: Diabetes Care (2012)

Few studies are currently available regarding the influence of sleep duration on glycemic control in diabetic patients. The objective of the current study was to examine the relationship between sleep duration, obesity, and the glycemic level in type 2 diabetic patients.A total of 4,870 Japanese type 2 diabetic patients aged ≥20 years were divided into six groups according to their self-reported sleep duration: less than 4.5 h, 4.5-5.4 h, 5.5-6.4 h, 6.5-7.4 h, 7.5-8.4 h, and more than 8.5 h. The associations of sleep duration with obesity and the HbA(1c) levels were examined in a cross-sectional manner.The HbA(1c) levels showed a quadratic association with sleep duration; namely, a shorter or longer sleep duration was associated with a higher level compared with a sleep duration of 6.5-7.4 h (P for quadratic trend <0.001). This association remained significant after adjusting for potential confounders, including the total energy intake and depressive symptoms. Furthermore, additional adjustments for obesity, which also showed a U-shaped relationship with sleep duration, did not attenuate the U-shaped sleep-HbA(1c) association. A significant interaction between sleep duration and age or the use of insulin was observed for the HbA(1c) levels.Sleep duration was shown to have U-shaped associations with obesity and the HbA(1c) levels in type 2 diabetic patients, independent of potential confounders, and therefore may be an important modifiable factor for the clinical management of patients with type 2 diabetes.
Strategies for Screening Blood for Human Immunodeficiency Virus Antibody
Authors: J. Sanford Schwartz
Journal: JAMA (1990)

A decision analytic model was used to examine alternative strategies to screen donated blood for human immunodeficiency virus (HIV) using data from the literature and from 1987 blood-screening programs in areas with high and low prevalence of HIV. Sensitivity analyses incorporated uncertainties about HIV infection and test performance. Current screening strategies are estimated to allow 20.5 infected units per million donated units to be transfused at a cost of $16 850 per HIV-positive unit detected in high-prevalence areas and 4.7 infected units per million donated units to be transfused at a cost of $32 275 per HIV-positive unit detected in low prevalence areas, with nine false-positive notifications of uninfected patients per million units screened and 14.9 discarded, noninfected units per HIV-positive unit in low-prevalence areas. Testing donated blood for HIV can be improved by individualizing screening strategies for areas with different prevalences of HIV. Efforts to further reduce transfusion-associated HIV should focus on improved test performance in early stages of infection, reduction of unnecessary transfusions, donor recruitment in lower-risk groups, and public health measures to reduce HIV infection among the general population. (<i>JAMA</i>. 1990;264:1704-1710)
Transmucosal potential difference; diagnostic value in gastro-oseophageal reflux.
Authors: B Khamis, C Kennedy, J Finucane, J S Doyle
Journal: Gut (1978)

Nineteen patients with symptoms of upper gastrointestinal disease were assessed by endoscopy. Transmucosal potential difference (PD) in the lower oesophagus was recorded and suction biopsy specimens were obtained from the site of measurement and examined by light microscopy after haematoxylin and eosin staining. In 10 patients with normal histology, mean PD was--14.4 mV (SEM +/- 0.4 mV), whereas in nine patients with histological changes of reflux mean was +9.4 mV (SEM +/- 3.0 mV). In this latter group, polarity of the PD was reversed in all but one case. Good correlation was found between these objective indices of lower oesophageal disease and the presence of symptoms such as dysphagia and heartburn. The visual appearance at endoscopy was less reliable. It is suggested that measurement of PD is a simple, rapid, and sensitive method of detecting the presence of oesophageal mucosal damage.
Determinants of a protective effect of glucose and insulin on the ischemic myocardium. Effects on contractile function, diastolic compliance, metabolism, and ultrastructure during ischemia and reperfusion.
Authors: C S Apstein, F N Gravino, C C Haudenschild
Journal: Circulation Research (1983)

The efficacy of hyperglycemia and insulin therapy for reducing ischemic myocardial injury is controversial and unproven. Accordingly, factors that might influence the effects of hyperglycemia and insulin were studied in isolated perfused rabbit hearts at two degrees of global ischemia, either "severe" or "moderate." During the ischemic period, different groups (n = 15-28/group) received either 100 mg/100 ml glucose-no insulin (control group), 500 mg/100 ml glucose + 100 mU/ml insulin (G + I), or 100 mg/100 ml glucose + 400 mg/100 ml mannitol (osmotic control). During moderate ischemia, effective washout of myocardial lactate was maintained, and hyperglycemia and insulin doubled the glycolytic flux, completely prevented contracture during ischemia, decreased contracture during reperfusion, increased recovery of postischemic contractile function, decreased ultrastructural damage, and increased high energy phosphate levels. Hyperglycemia and insulin increased glycolytic flux only after 30 minutes of ischemia had elapsed, suggesting that endogenous glycogen provided adequate glycolytic substrate prior to this time. The mannitol-glucose substrate had no beneficial effects, indicating that the hyperglycemia and insulin substrate had a metabolic rather than an osmotic mechanism of action. In contrast, during severe ischemia, tissue lactate washout was ineffective; the hyperglycemia and insulin substrate increased glycolytic flux by only 15% and produced no persistent beneficial effects. These results suggest that hyperglycemia and insulin therapy is beneficial to the ischemic myocardium when two conditions are met. First, the degree of myocardial perfusion, although in the ischemic range, must be adequate to prevent the accumulation of high tissue levels of lactate which inhibit glycolysis and prevent any glycolytic stimulation by hyperglycemia and insulin. Second, the ischemic myocardium must be "glucose dependent" for glycolytic substrate; in our studies this occurred after 30-45 minutes of sustained ischemia, probably because myocardial glycogen stores became depleted.
Antimicrobial Actions of the Nadph Phagocyte Oxidase and Inducible Nitric Oxide Synthase in Experimental Salmonellosis. I. Effects on Microbial Killing by Activated Peritoneal Macrophages in Vitro
Authors: Andrés Vazquez-Torres, Jessica Jones-Carson, Pietro Mastroeni, Harry Ischiropoulos, Ferric C. Fang
Journal: The Journal of Experimental Medicine (2000)

The contribution of the NADPH phagocyte oxidase (phox) and inducible nitric oxide (NO) synthase (iNOS) to the antimicrobial activity of macrophages for Salmonella typhimurium was studied by using peritoneal phagocytes from C57BL/6, congenic gp91phox(-/)-, iNOS(-/)-, and doubly immunodeficient phox(-/)-iNOS(-/)- mice. The respiratory burst and NO radical (NO.) made distinct contributions to the anti-Salmonella activity of macrophages. NADPH oxidase-dependent killing is confined to the first few hours after phagocytosis, whereas iNOS contributes to both early and late phases of antibacterial activity. NO-derived species initially synergize with oxyradicals to kill S. typhimurium, and subsequently exert prolonged oxidase-independent bacteriostatic effects. Biochemical analyses show that early killing of Salmonella by macrophages coincides with an oxidative chemistry characterized by superoxide anion (O(2).(-)), hydrogen peroxide (H(2)O(2)), and peroxynitrite (ONOO(-)) production. However, immunofluorescence microscopy and killing assays using the scavenger uric acid suggest that peroxynitrite is not responsible for macrophage killing of wild-type S. typhimurium. Rapid oxidative bacterial killing is followed by a sustained period of nitrosative chemistry that limits bacterial growth. Interferon gamma appears to augment antibacterial activity predominantly by enhancing NO. production, although a small iNOS-independent effect was also observed. These findings demonstrate that macrophages kill Salmonella in a dynamic process that changes over time and requires the generation of both reactive oxidative and nitrosative species.
Guanosine nucleotides inhibit different syndromes of PTHrP excess caused by human cancers in vivo
Authors: Wolfgang E. Gallwitz, Theresa A. Guise, Gregory R. Mundy
Journal: Journal of Clinical Investigation (2002)

There are two well-described syndromes caused by tumor production of parathyroid hormone-related peptide (PTHrP), namely osteolytic bone disease associated with breast cancer and humoral hypercalcemia of malignancy (HHM) that occurs with or without bone metastasis. Both syndromes have been shown experimentally to be inhibited by neutralizing antibodies to PTHrP. In a search for small-molecule inhibitors of PTHrP production or effects, we have identified guanine-nucleotide analogs as compounds that inhibit PTHrP expression by human tumor cells associated with these syndromes. We show in nude athymic murine models that these compounds reduce PTHrP-mediated osteolytic lesions associated with metastatic human breast-cancer cells as well as the degree of hypercalcemia caused by excessive PTHrP production by a squamous-cell carcinoma of the lung. These results suggest that the PTHrP gene promoter may be a suitable target for treating the skeletal effects of malignancy.
EGFR Expression Predicts BRCA1 Status in Patients with Breast Cancer
Authors: Paul J. van Diest, Petra van der Groep, Elsken van der Wall
Journal: Clinical Cancer Research (2006)

To the Editor: In their article, Lakhani et al. ([1][1]) report on the value of basal phenotype markers for the prediction of BRCA1 status. One of the useful features pointing to “BRCA1-ness” appeared to be high expression of the epidermal growth factor receptor (EGFR). No rationale is given by
IL-4–Stat6 Signaling Induces Tristetraprolin Expression and Inhibits TNF-α Production in Mast Cells
Authors: Kotaro Suzuki, Hiroshi Nakajima, Kei Ikeda, Yuko Maezawa, Akira Suto, Hiroaki Takatori, Yasushi Saito, Itsuo Iwamoto
Journal: The Journal of Experimental Medicine (2003)

Increasing evidence has revealed that mast cell–derived tumor necrosis factor α (TNF-α) plays a critical role in a number of inflammatory responses by recruiting inflammatory leukocytes. In this paper, we investigated the regulatory role of interleukin 4 (IL-4) in TNF-α production in mast cells. IL-4 inhibited immunoglobulin E–induced TNF-α production and neutrophil recruitment in the peritoneal cavity in wild-type mice but not in signal transducers and activators of transcription 6 (Stat6)–deficient mice. IL-4 also inhibited TNF-α production in cultured mast cells by a Stat6-dependent mechanism. IL-4–Stat6 signaling induced TNF-α mRNA destabilization in an AU-rich element (ARE)–dependent manner, but did not affect TNF-α promoter activity. Furthermore, IL-4 induced the expression of tristetraprolin (TTP), an RNA-binding protein that promotes decay of ARE-containing mRNA, in mast cells by a Stat6-dependent mechanism, and the depletion of TTP expression by RNA interference prevented IL-4–induced down-regulation of TNF-α production in mast cells. These results suggest that IL-4–Stat6 signaling induces TTP expression and, thus, destabilizes TNF-α mRNA in an ARE-dependent manner.
Immunostimulatory Tim-1–specific antibody deprograms Tregs and prevents transplant tolerance in mice
Authors: Nicolas Degauque, Christophe Mariat, James Kenny, Dong Zhang, Wenda Gao, Minh Diem Vu, Sophoclis Alexopoulos, Mohammed Oukka, Dale T. Umetsu, Rosemarie H. DeKruyff, Vijay Kuchroo, Xin Xiao Zheng, Terry B. Strom
Journal: Journal of Clinical Investigation (2008)

T cell Ig mucin (Tim) molecules modulate CD4+ T cell responses. In keeping with the view that Tim-1 generates a stimulatory signal for CD4+ T cell activation, we hypothesized that an agonist Tim-1–specific mAb would intensify the CD4+ T cell–dependant allograft response. Unexpectedly, we determined that a particular Tim-1–specific mAb exerted reciprocal effects upon the commitment of alloactivated T cells to regulatory and effector phenotypes. Commitment to the Th1 and Th17 phenotypes was fostered, whereas commitment to the Treg phenotype was hindered. Moreover, ligation of Tim-1 in vitro effectively deprogrammed Tregs and thus produced Tregs unable to control T cell responses. Overall, the effects of the agonist Tim-1–specific mAb on the allograft response stemmed from enhanced expansion and survival of T effector cells; a capacity to deprogram natural Tregs; and inhibition of the conversion of naive CD4+ T cells into Tregs. The reciprocal effects of agonist Tim-1–specific mAbs upon effector T cells and Tregs serve to prevent allogeneic transplant tolerance.
A Comparative Effectiveness Analysis of Three Continuous Glucose Monitors
Authors: Edward R. Damiano, Firas H. El-Khatib, Hui Zheng, David M. Nathan, Steven J. Russell
Journal: Diabetes Care (2012)

To compare three continuous glucose monitoring (CGM) devices in subjects with type 1 diabetes under closed-loop blood glucose (BG) control.Six subjects with type 1 diabetes (age 52 ± 14 years, diabetes duration 32 ± 14 years) each participated in two 51-h closed-loop BG control experiments in the hospital. Venous plasma glucose (PG) measurements (GlucoScout, International Biomedical) obtained every 15 min (2,360 values) were paired in time with corresponding CGM glucose (CGMG) measurements obtained from three CGM devices, the Navigator (Abbott Diabetes Care), the Seven Plus (DexCom), and the Guardian (Medtronic), worn simultaneously by each subject. Errors in paired PG-CGMG measurements and data reporting percentages were obtained for each CGM device.The Navigator had the best overall accuracy, with an aggregate mean absolute relative difference (MARD) of all paired points of 11.8 ± 11.1% and an average MARD across all 12 experiments of 11.8 ± 3.8%. The Seven Plus and Guardian produced aggregate MARDs of all paired points of 16.5 ± 17.8% and 20.3 ± 18.0%, respectively, and average MARDs across all 12 experiments of 16.5 ± 6.7% and 20.2 ± 6.8%, respectively. Data reporting percentages, a measure of reliability, were 76% for the Seven Plus and nearly 100% for the Navigator and Guardian.A comprehensive head-to-head-to-head comparison of three CGM devices for BG values from 36 to 563 mg/dL revealed marked differences in performance characteristics that include accuracy, precision, and reliability. The Navigator outperformed the other two in these areas.
Total Versus Hemithyroidectomy for Well Differentiated Thyroid Cancer
Authors: S. Kuba, K. Yamanouchi, C. Sakimura, F. Kawakami, S. Minami, F. Fujita, M. Takatsuki, K. Kobayashi, K. Kanetaka, T. Kuroki, S. Eguchi
Journal: Annals of Oncology (2014)
Platelet dysfunction in myeloproliferative syndromes
Authors: Kiran Phadke, Shirley Dean, W. R. Pitney
Journal: American Journal of Hematology (1981)

Abstract The most common abnormality of the platelets in 43 patients with a variety of myeloproliferative syndromes was impaired or absent aggregation when stimulated with collagen and adrenaline. Eight unselected cases studied in more detail showed a normal prostaglandin synthesis pathway as evidenced by normal aggregation with arachidonic acid and the production of normal amounts of malonyldialdehyde. Mixing experiments with aspirin‐tested platelets showed correction of the abnormal adrenaline and collagen responses and confirmed that the nature of the defect was different from that induced by aspirin. Stimulation of “myeloproliferative” platelets with thrombin after blocking the prostaglandin pathway with aspirin resulted in reduced aggregation, indicating either a deficiency of the storage pool of adenine nucleotides in the platelets or an abnormality of a membrane receptor for thrombin.
Indanocine, a Microtubule-Binding Indanone and a Selective Inducer of Apoptosis in Multidrug-Resistant Cancer Cells
Authors: Lorenzo M. Leoni, Ernest Hamel, Davide Genini, Hsiencheng Shih, Carlos J. Carrera, Howard B. Cottam, Dennis A. Carson
Journal: JNCI Journal of the National Cancer Institute (2000)

Certain antimitotic drugs have antitumor activities that apparently result from interactions with nontubulin components involved in cell growth and/or apoptotic cell death. Indanocine is a synthetic indanone that has been identified by the National Cancer Institute's Developmental Therapeutics Program as having antiproliferative activity. In this study, we characterized the activity of this new antimitotic drug toward malignant cells.We tested antiproliferative activity with an MTT [i.e., 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay, mitochondrial damage and cell cycle perturbations with flow cytometry, caspase-3 activation with fluorometry, alterations of the cytoskeletal components with immunofluorescence, and antimicrotubule activity with a tubulin polymerization assay.Indanocine is a cytostatic and cytotoxic indanone that blocks tubulin polymerization but, unlike other antimitotic agents, induces apoptotic cell death in stationary-phase multidrug-resistant cancer cells at concentrations that do not impair the viability of normal nonproliferating cells. Of the seven multidrug-resistant cell lines tested, three (i.e., MCF-7/ADR, MES-SA/DX5, and HL-60/ADR) were more sensitive to growth inhibition by indanocine than were their corresponding parental cells. Confluent multidrug-resistant cells (MCF-7/ADR), but not drug-sensitive cancer cells (MCF-7) or normal peripheral blood lymphocytes, underwent apoptotic cell death 8-24 hours after exposure to indanocine, as measured by sequential changes in mitochondrial membrane potential, caspase activity, and DNA fragmentation. Indanocine interacts with tubulin at the colchicine-binding site, potently inhibits tubulin polymerization in vitro, and disrupts the mitotic apparatus in dividing cells.The sensitivity of stationary multidrug-resistant cancer cells to indanocine suggests that indanocine and related indanones be considered as lead compounds for the development of chemotherapeutic strategies for drug-resistant malignancies.
The Surgery of the Gall Bladder and Bile Ducts, with Brief Notes of 78 Cases
Authors: A. W. M. Robson
Journal: BMJ (1894)

After-Ilistory.53 E. B. F 44 6-5 93 Cholecystotomy Contracted gall bladder; 2 stoncs in cystic duct; R Well when last hleard of.crushed 60 H