tbuckley/cabot-search huggingface dataset:
Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.
Authors: F Sallusto, A Lanzavecchia
Journal: The Journal of Experimental Medicine (1994)

Using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 we have established dendritic cell (DC) lines from blood mononuclear cells that maintain the antigen capturing and processing capacity characteristic of immature dendritic cells in vivo. These cells have typical dendritic morphology, express high levels of major histocompatibility complex (MHC) class I and class II molecules, CD1, Fc gamma RII, CD40, B7, CD44, and ICAM-1, and lack CD14. Cultured DCs are highly stimulatory in mixed leukocyte reaction (MLR) and are also capable of triggering cord blood naive T cells. Most strikingly, these DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones. Their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR-mediated antigen uptake. Incubation of these cultured DCs with tumor necrosis factor alpha (TNF-alpha) or soluble CD40 ligand (CD40L) for 24 h results in an increased surface expression of MHC class I and class II molecules, B7, and ICAM-1 and in the appearance of the CD44 exon 9 splice variant (CD44-v9); by contrast, Fc gamma RII is markedly and sometimes completely downregulated. The functional consequences of the short contact with TNF-alpha are in increased T cell stimulatory capacity in MLR, but a 10-fold decrease in presentation of soluble TT and a 100-fold decrease in presentation of TT-immunoglobulin G complexes.
Prevention of Radiation-Induced Oral Mucositis after Adenoviral Vector–Mediated Transfer of the Keratinocyte Growth Factor cDNA to Mouse Submandibular Glands
Authors: Changyu Zheng, Ana P. Cotrim, Abraham N. Sunshine, Takayuki Sugito, Lina Liu, Anastasia Sowers, James B. Mitchell, Bruce J. Baum
Journal: Clinical Cancer Research (2009)

The study aims to evaluate if human keratinocyte growth factor (hKGF), secreted after transduction of murine salivary glands with adenoviral vectors, can prevent oral mucositis resulting from radiation.Two serotype 5 adenoviral vectors encoding hKGF were constructed: AdEF1alpha-hKGF and AdLTR(2)EF1alpha-hKGF. Female C3H mice, 8 weeks old, were irradiated by single (22.5 Gy) or fractionated (5 x 8 Gy for 5 days) doses to induce oral mucositis (ulcers on tongue). One day before irradiation, the above viral vectors or an empty vector, Adcontrol, was given (10(10) particles per gland) to both submandibular glands by retrograde ductal instillation. Each experiment included five groups: no irradiation and irradiation (+/-Adcontrol, AdEF1alpha-hKGF, or AdLTR(2)EF1alpha-hKGF). Blood, saliva, submandibular glands, and tongue were collected on day 7 for single-dose studies or day 10 for fractionated dosing. hKGF levels were measured by ELISA.In three separate single-dose irradiation experiments, lingual ulcers were dramatically reduced after either KGF-expressing vector. Similarly, in two separate fractionated irradiation experiments, the hKGF-expressing vectors completely prevented ulcer formation. QPCR data indicated that approximately 10(7) to 10(8) particles of each vector remained in the targeted submandibular glands at the terminal time. Transgenic hKGF protein was found at high levels in saliva, serum, and submandibular gland extracts.hKGF gene transfer to salivary glands prevented radiation-induced oral mucositis in mice. This proof of concept study suggests that transgenic hKGF secreted from transduced salivary glands may be useful clinically to prevent oral mucositis caused by radiation.
Vascular Muscle Reactivity
Authors: W. ALAN DODD, EDWIN E. DANIEL
Journal: Circulation Research (1960)

Arterial contractility was investigated, using spiral and ring sections of dog, cat, rabbit, rat, and human vessels. Epinephrine produced contractions of all arterial tissue tested. Histamine invariably produced contractions. The phenomenon of variable sensitivity of arterial tissue to histamine was again demonstrated. Acetylcholine caused contractions of rabbit, cat, and rat aortas, but no contraction of the dog aorta, or dog and human femoral arteries was observed. Pitressin produced contraction of the rat aorta, and dog and human femoral arteries, but not of rabbit, dog or cat aortas. Using dog vessels, a difference in activity was observed between the aorta and the femoral artery. Greater reactivity in terms of maximum rate of tension increase and tension developed was seen in the smaller systemic arteries. A pharmacologic difference with respect to the action of pitressin was discovered between the aorta and the smaller arteries. Thus, general evidence is presented suggesting that data obtained in 1 species of animal on 1 type of tissue cannot be transferred without specific proof of its validity to data obtained in other species, or even in closely related tissues of the same species. An apparent antagonistic effect of pitressin on the pressor action of epinephrine was detected.
STUDIES ON THE TREATMENT OF HUMAN TRYPANOSOMIASIS WITH TRYPARSAMIDE (THE SODIUM SALT OF N-PHENYLGLYCINEAMIDE-p-ARSONIC ACID)
Authors: L. Pearce
Journal: The Journal of Experimental Medicine (1921)

Dosesof 4.0 to 7.0 gm.80 to 112 nag.per kg.6 '1 3 2 12 12TREATMENT OF HUMAN TRYPANOSOMIASIS 5 of the 11 showed negative blood examinations within 9 hours after treatment, and 10 were negative within 15 hours.Combining the results of these doses with those of 51 to 70 rag.per kilo as shown in the second and third columns, 15 out of the 20 patients so treated were negative within 15 hours.Somewhat larger doses of 2.0 to 5.0 gm or 71 to 109 rag.per kilo of body weight were given to 9 patients, all of whom were negative in 15 hours and 6 negative within 9 hours after treatment.As in the microscopic examination of lymph gland juice, it was not possible to make complete series of observations.In these 35 patients, the last positive blood examinations occurred from 3 to 8 hours after treatment with doses of 1.0 to 3.0 gin.or 18 to 51 rag.per kilo.The following examples illustrate these points: Molalo ~ 60.Tryparsamide 1.0 gin.or 20 nag. per kilo.Centrifuged blood: 16 hours 0. Maf~xtla ~¢ 30.Tryparsamide 1.0 gin.or 25 nag.per kilo.Centrifuged blood: 6 hours 0. Mago lg 28.Tryparsamide 1.0 gin.or 33 rag.per kilo.Centrifuged blood: 7½ hours 0. Messamba ~ 57.Tryparsamide 2.0 gin.or 39 rag.per kilo.Centrifuged blood: 7 hours +; 21 hours 0. Mtmdi ~ 75.Tryparsamide 2.0 gin.or 44 rag.per kilo.Centrifuged blood: 3½ hours 0. Mulamba ~39.Tryparsamide 3.0 gin.or 51 rag.per kilo.: Centrifuged blood: 3 hours +; 8 hours 0. Mom~eke ~t 47.Tryparsamide 4.0 gin.or 66 rag.per kilo.Centrifuged blood: 6½ hours 0. Mambula ~¢43.Tryparsamide 2.0 gin.or 71 nag.per kilo.Centrifuged blood: 6 hours +; 8 hours 0. Bajaka ~¢ 41.Tryparsamide 4.0 gin.or 76 rag.per kilo.Centrifuged blood: 15 hours 0. Bikoko ~t 55.Tryparsamide 5.0 gin.or 80 nag.per kilo.Centrifuged blood: 5 hours 0. Admitted to lazaret July 14, 1920.47 kilos.Cervical lymph glands enlarged.Gland puncture q-.Lumbar puncture 7.5 lymphocytes per cram.lOgO July 14, 10 a.m.Tryparsamide 2.0 gin.(13 nag.per kg.) adm.i.v.11 a.m. 1 hour after treatment G. P. -b " 30, Tryparsamide 0.5 gin.(2nd Provocative dose).Nov. 2, G .P .0 C .B .0. C .B .O ~¢ ~¢ 0 g~ ~g 0 ~ ¢¢ 0 ~¢ ¢¢ 0 " " 0" " 0 L.
Protective role of Nd1 in doxorubicin-induced cardiotoxicity
Authors: L FUJIMURA, Y MATSUDO, M KANG, Y TAKAMORI, T TOKUHISA, M HATANO
Journal: Cardiovascular Research (2004)

The Ndl gene, which encodes a novel kelch family protein, is expressed ubiquitously in mouse tissues. In vitro studies suggest that Ndl protein, which binds to actin filaments, functions as a cytoskeletal stabilizer. In order to elucidate a physiological function of Ndl in vivo, we generated Nd1-deficient (Ndl-/-) mice.We developed Nd1-/- mice by standard gene targeting technique. Cardiac function was studied in wild type and Nd1-/- mice.Nd1-/- mice were viable and no gross anatomical abnormality was observed after birth. When mouse embryonic fibroblasts were cultured in the presence of cytochalasin D or doxorubicin, the number of apoptotic cells in the Nd1-/- cell culture was larger that that in the wild-type cell culture. Furthermore, Nd1-/- mice were sensitive to doxorubicin-induced cardiotoxicity with increased numbers of cardiomyocytes apoptosis.Although Nd1 is dispensable for normal mice development, Nd1 plays a protective role in doxorubicin-induced cardiotoxic responses.
Arrhythmogenic Mechanism of an LQT-3 Mutation of the Human Heart Na <sup>+</sup> Channel α-Subunit
Authors: X. H. T. Wehrens, H. Abriel, C. Cabo, J. Benhorin, R. S. Kass
Journal: Circulation (2000)

D1790G, a mutation of SCN5A, the gene that encodes the human Na(+) channel alpha-subunit, is linked to 1 form of the congenital long-QT syndrome (LQT-3). In contrast to other LQT-3-linked SCN5A mutations, D1790G does not promote sustained Na(+) channel activity but instead alters the kinetics and voltage-dependence of the inactivated state.We modeled the cardiac ventricular action potential (AP) using parameters and techniques described by Luo and Rudy as our control. On this background, we modified only the properties of the voltage-gated Na(+) channel according to our patch-clamp analysis of D1790G channels. Our results indicate that D1790G-induced changes in Na(+) channel activity prolong APs in a steeply heart rate-dependent manner not directly due to changes in Na(+) entry through mutant channels but instead to alterations in the balance of net plateau currents by modulation of calcium-sensitive exchange and ion channel currents.We conclude that the D1790G mutation of the Na(+) channel alpha-subunit can prolong the cardiac ventricular AP despite the absence of mutation-induced sustained Na(+) channel current. This prolongation is calcium-dependent, is enhanced at slow heart rates, and at sufficiently slow heart rate triggers arrhythmogenic early afterdepolarizations.
Molecular Pathways: P-Rex in Cancer
Authors: Atanasio Pandiella, Juan Carlos Montero
Journal: Clinical Cancer Research (2013)

Abstract P-Rex proteins are Rho/Rac guanine nucleotide exchange factors that participate in the regulation of several cancer-related cellular functions such as proliferation, motility, and invasion. Expectedly, a significant portion of these actions of P-Rex proteins must be related to their Rac regulatory properties. In addition, P-Rex proteins control signaling by the phosphoinositide 3-kinase (PI3K) route by interacting with PTEN and mTOR. The interaction with PTEN inhibits its phosphatase activity, leading to AKT activation. The interaction with mTOR may be important in nutrient-stimulated Rac activation and migration. In humans, several studies have implicated P-Rex proteins in the pathophysiology of various neoplasias. Thus, overexpression of P-Rex proteins has been linked to poor patient outcome in breast cancer and may facilitate metastatic dissemination of prostate cancer cells. In addition, whole-genome sequencing described P-Rex2 as a significantly mutated gene in melanoma. Furthermore, expression in melanocytes of mutated forms of P-Rex2 found in patients with melanoma showed the protumorigenic role of these P-Rex mutations in melanoma genesis. These findings open interesting opportunities for P-Rex targeting in cancer. Moreover, the implication of P-Rex partner proteins such as Rac, mTOR, or PTEN in cancer has opened the possibility of acting on P-Rex to restrict protumorigenic signaling through these pathways. Clin Cancer Res; 19(17); 4564–9. ©2013 AACR.
Suppression of in vitro antibody synthesis by immunoglobulin-binding factor.
Authors: R H Gisler, W H Fridman
Journal: The Journal of Experimental Medicine (1975)

Alloantigen-activated mouse T cells secrete a factor which binds to the Fc fragment of IgG and blocks complement (C) activation by IgG (immunoglobulin-binding factor, IBF). IBF was found to suppress the direct plaque-forming cell (PFC) response of mouse spleen cell cultures to sheep erythrocytes and to dinitrophenylated aminoethyldextran (T-independent antigen). Purification of IBF by affinity chromatography on IgG-coated Sepharose columns led to an increase of the suppressive capacity with IgG, IgM, or Fab2 from IgG) the factor responsible for inhibiting the PFC response could not be dissociated from that responsible for the inhibitory activity of IBF on C-dependent hemolysis. No effect was seen when cultures were pretreated for 6 h, or when IBF was added at 72 h. These data are compatible with the view that IBF is a soluable mediator of suppressor T cells which may interfere with terminal differentiation of antibody-forming cell precursors.
A phase II study of ZD0473 given as a short infusion every 3 weeks to patients with advanced or metastatic breast cancer: a National Cancer Institute of Canada Clinical Trials Group trial, IND 129
Authors: K.A. Gelmon, T.A. Vandenberg, L. Panasci, B. Norris, M. Crump, L. Douglas, W. Walsh, S.J. Matthews, L.K. Seymour
Journal: Annals of Oncology (2003)
The common mechanisms of anterior cruciate ligament injuries in judo: a retrospective analysis
Authors: S Koshida, T Deguchi, K Miyashita, K Iwai, Y Urabe
Journal: British Journal of Sports Medicine (2008)

Although high prevalence of anterior cruciate ligament injuries (ACL) in judokas has been reported, there has been very little research concerning events preceding the injury.To determine the common situations and mechanisms of ACL injury in judo.A total of 43 cases of ACL injuries that had occurred during judo competition or practice were investigated, using questionnaires with interviews conducted by a single certified athletic trainer who has 20 years of judo experience to obtain information regarding the situation and mechanism in which the ACL injury occurred.The number of ACL injuries when the participant's grip style was different from the style of the opponent (ie, kenka-yotsu style) (28 cases) was significantly greater than when the participant's grip style was the same as that of the opponent (ie, ai-yotsu style) (15 cases; p<0.001). The number of ACL injuries was significantly higher when the participant was attacked by the opponent than when counterattacked or when attempting the attack (p<0.001). In addition, being attacked with osoto-gari was revealed as the leading cause of ACL injury incidence among the participants (16.8%).Grip style may be associated with ACL injury occurrence in judo. In addition, direct contact due to the opponent's attack may be a common mechanism for ACL injuries in judo.
Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation
Authors: Robert R. Jenq, Carles Ubeda, Ying Taur, Clarissa C. Menezes, Raya Khanin, Jarrod A. Dudakov, Chen Liu, Mallory L. West, Natalie V. Singer, Michele J. Equinda, Asia Gobourne, Lauren Lipuma, Lauren F. Young, Odette M. Smith, Arnab Ghosh, Alan M. Hanash, Jenna D. Goldberg, Kazutoshi Aoyama, Bruce R. Blazar, Eric G. Pamer, Marcel R.M. van den Brink
Journal: The Journal of Experimental Medicine (2012)

Despite a growing understanding of the link between intestinal inflammation and resident gut microbes, longitudinal studies of human flora before initial onset of intestinal inflammation have not been reported. Here, we demonstrate in murine and human recipients of allogeneic bone marrow transplantation (BMT) that intestinal inflammation secondary to graft-versus-host disease (GVHD) is associated with major shifts in the composition of the intestinal microbiota. The microbiota, in turn, can modulate the severity of intestinal inflammation. In mouse models of GVHD, we observed loss of overall diversity and expansion of Lactobacillales and loss of Clostridiales. Eliminating Lactobacillales from the flora of mice before BMT aggravated GVHD, whereas reintroducing the predominant species of Lactobacillus mediated significant protection against GVHD. We then characterized gut flora of patients during onset of intestinal inflammation caused by GVHD and found patterns mirroring those in mice. We also identified increased microbial chaos early after allogeneic BMT as a potential risk factor for subsequent GVHD. Together, these data demonstrate regulation of flora by intestinal inflammation and suggest that flora manipulation may reduce intestinal inflammation and improve outcomes for allogeneic BMT recipients.
Health-Related Quality of Life, Treatment Satisfaction, and Costs Associated With Intraperitoneal Versus Subcutaneous Insulin Administration in Type 1 Diabetes
Authors: Susan J. Logtenberg, Nanne Kleefstra, Sebastiaan T. Houweling, Klaas H. Groenier, Reinold O. Gans, Henk J. Bilo
Journal: Diabetes Care (2010)

To investigate the effects of continuous intraperitoneal insulin infusion (CIPII) compared with subcutaneous insulin on health-related quality of life (HRQOL) and treatment satisfaction, and to perform a cost analysis in type 1 diabetes.We used an open-label, prospective, crossover, randomized, 16-month study (N = 24). HRQOL and patient satisfaction were assessed with questionnaires (the 36-item short-form health survey [SF-36], the World Health Organization-Five Well-Being Index [WHO-5], and the Diabetes Treatment Satisfaction Questionnaire [DTSQ]). Direct costs of CIPII and continuous subcutaneous insulin infusion (CSII) were compared.Questionnaire scores were higher with CIPII than with subcutaneous therapy. Yearly direct pump- and procedure-associated costs for CIPII were estimated at 10,910 euroscompared with 4,810 euros for CSII.Apart from improving glycemic control, CIPII improved HRQOL and treatment satisfaction compared with subcutaneous insulin. Direct pump- and procedure-associated costs are considerably higher for CIPII, however.
Multimodal Elucidation of Choline Metabolism in a Murine Glioma Model Using Magnetic Resonance Spectroscopy and 11C-Choline Positron Emission Tomography
Authors: Hans F. Wehrl, Julian Schwab, Kathy Hasenbach, Gerald Reischl, Ghazaleh Tabatabai, Leticia Quintanilla-Martinez, Filip Jiru, Kamila Chughtai, Andras Kiss, Funda Cay, Daniel Bukala, Ron M.A. Heeren, Bernd J. Pichler, Alexander W. Sauter
Journal: Cancer Research (2013)

The metabolites, transporters, and enzymes involved in choline metabolism are regarded as biomarkers for disease progression in a variety of cancers, but their in vivo detection is not ideal. Both magnetic resonance spectroscopy [MRS using chemical shift imaging (CSI) total choline (tCho)] and C-choline positron emission tomography (PET) can probe this pathway, but they have not been compared side by side. In this study, we used the spontaneous murine astrocytoma model SMA560 injected intracranially into syngeneic VM/Dk mice, analyzing animals at various postimplantation time points using dynamic microPET imaging and CSI MRS. We observed an increase in tumor volume and C-choline uptake between days 5 and 18. Similarly, tCho levels decreased at days 5 to 18. We found a negative correlation between the tCho and PET results in the tumor and a positive correlation between the tCho tumor-to-brain ratio and choline uptake in the tumor. PCR results confirmed expected increases in expression levels for most of the transporters and enzymes. Using MRS quantification, a good agreement was found between CSI and C-choline PET data, whereas a negative correlation occurred when CSI was not referenced. Thus, C-choline PET and MRS methods seemed to be complementary in strengths. While advancing tumor proliferation caused an increasing C-choline uptake, gliosis and inflammation potentially accounted for a high peritumoral tCho signal in CSI, as supported by histology and secondary ion mass spectrometry imaging. Our findings provide definitive evidence of the use of MRS, CSI, and PET for imaging tumors in vivo.
Survival in End-Stage Dementia Following Acute Illness
Authors: R. Sean Morrison
Journal: JAMA (2000)

Little is known about the prognosis of acutely ill patients with end-stage dementia or about the type of care that these patients receive. If their prognosis is poor, then emphasis should be placed on palliative care for these patients rather than on curative interventions.To examine survival for patients with end-stage dementia following hospitalization for hip fracture or pneumonia and to compare their care with that of cognitively intact older adults.Prospective cohort study with 6 months of follow-up.Patients aged 70 years or older who were hospitalized with hip fracture (cognitively intact, n=59; with end-stage dementia, n=38) or pneumonia (cognitively intact, n=39; with end-stage dementia, n=80) in a large hospital in New York, NY, between September 1, 1996, and March 1, 1998.Mortality, treatments directed at symptoms, and application of distressing and painful procedures in cognitively intact patients vs those with end-stage dementia.Six-month mortality for patients with end-stage dementia and pneumonia was 53% (95% confidence interval [CI], 41%-64%) compared with 13% (95% CI, 4%-27%) for cognitively intact patients (adjusted hazard ratio, 4.6; 95% CI, 1.8-11.8). Six-month mortality for patients with end-stage dementia and hip fracture was 55% (95% CI, 42%-75%) compared with 12% (95% CI, 5%-24%) for cognitively intact patients (adjusted hazard ratio, 5.8; 95% CI, 1.7-20.4). Patients with end-stage dementia received as many burdensome procedures as cognitively intact patients and only 8 (7%) of 118 patients with end-stage dementia had a documented decision made to forego a life-sustaining treatment other than cardiopulmonary resuscitation. Only 24% of patients with end-stage dementia and hip fracture received a standing order for analgesics.In this study, patients with advanced dementia and hip fracture or pneumonia had a very poor prognosis. Given the limited life expectancy of patients with end-stage dementia following these illnesses and the burdens associated with their treatment, increased attention should be focused on efforts to enhance comfort in this patient population. JAMA. 2000;284:47-52
Second malignant neoplasms in children: an update from the Late Effects Study Group.
Authors: A T Meadows, E Baum, F Fossati-Bellani, D Green, R D Jenkin, B Marsden, M Nesbit, W Newton, O Oberlin, S G Sallan
Journal: Journal of Clinical Oncology (1985)

This paper presents an update from the Late Effects Study Group on 292 cases of second malignant neoplasms (SMN) occurring in individuals who were diagnosed with their first neoplasm in childhood. Data are presented regarding the types of first and second neoplasm, the therapy administered, and the predisposing factors. Of the 292 cases (308 SMN), the most common primary was retinoblastoma followed by Hodgkin's disease, soft-tissue sarcomas, and Wilms' tumor. This is not similar to the relative frequency of these cancers in children but rather reflects specific risk factors. Bone sarcomas were the most common SMN among the 208 SMN developing in previously irradiated sites while acute leukemia was the most common SMN unassociated with radiation. Known predisposing conditions to cancer were present in 73 cases; retinoblastoma was the most common of these, followed by neurofibromatosis. There were ten patients with three and three patients with four malignant neoplasms. In 14 patients, the cause of SMN was not suggested by known risk factors as these patients had negative family histories and received no radiation or chemotherapy. We note, therefore, that although most cases of SMN in survivors of childhood cancer can be attributed to radiation, genetic disease, chemotherapy, or combinations of these, unrecognized predisposition or chance may also play a role.