tbuckley/cabot-search huggingface dataset:
Endothelial Cell Dysfunction in Mice After Transgenic Knockout of Type 2, but Not Type 1, 11β-Hydroxysteroid Dehydrogenase
Authors: Patrick W.F. Hadoke, Clare Christy, Yuri V. Kotelevtsev, Brent C. Williams, Christopher J. Kenyon, Jonathan R. Seckl, John J. Mullins, Brian R. Walker
Journal: Circulation (2001)

11beta-Hydroxysteroid dehydrogenase (11betaHSD) isozymes catalyze the interconversion of active and inactive glucocorticoids, allowing local regulation of corticosteroid receptor activation. Both are present in the vessel wall; here, using mice with selective inactivation of 11betaHSD isozymes, we test the hypothesis that 11betaHSDs influence vascular function.Thoracic aortas were obtained from weight-matched male wild-type (MF1x129 cross(+/+)), 11betaHSD1(-/-), and 11betaHSD2(-/-) mice. mRNA for both isozymes was detected in wild-type aortas by RT-PCR. 11betaHSD activity in aortic homogenates (48.81+/-4.65% conversion) was reduced in both 11betaHSD1(-/-) (6.36+/-2.47% conversion; P<0.0002) and 11betaHSD2(-/-) (24.71+/-3.69; P=0.002) mice. Functional responses were unaffected in aortic rings isolated from 11betaHSD1(-/-) mice. In contrast, aortas from 11betaHSD2(-/-) mice demonstrated selectively enhanced constriction to norepinephrine (E(max) 4.28+/-0.56 versus 1.72+/-0.47 mN/mm; P=0.004) attributable to impaired endothelium-derived nitric oxide activity. Relaxation responses to endothelium-dependent and -independent vasodilators were also impaired. To control for chronic renal mineralocorticoid excess, MF1 mice were treated with fludrocortisone (16 weeks) but did not reproduce the functional changes observed in 11betaHSD2(-/-) mice.Although both 11betaHSD isozymes are present in the vascular wall, reactivation of glucocorticoids by 11betaHSD1 does not influence aortic function. Mice with 11betaHSD2 knockout, however, have endothelial dysfunction causing enhanced norepinephrine-mediated contraction. This appears to be independent of renal sodium retention and may contribute to hypertension in 11betaHSD2 deficiency.
Measurement of emphysema in autopsy lungs, with emphasis on interlobar differences.
Authors: K Saito, W M Thurlbeck
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

This study clarifies interlobar differences in the severity of emphysema and examines the feasibility of assessing emphysema in a whole lung using either the upper or lower lobes. Midsagittal, paper-mounted whole-lung sections from 79 consecutive autopsies were used. The whole-lung sections were scored by comparing them with the panel of standard pictures from Grades 0 to 100, after which the upper or lower lobes were scored in the same way but with the other lobe covered. Scores made on lobes and whole lungs correlated significantly, but while projections to whole-lung scores were quite accurate from the upper lobe, the projections from the lower lobe were less precise. This was particularly true in patients with mild emphysema. Individual lobes of the same lung sections were assessed by the Ryder grid method. This analysis showed that emphysema was more severe in the upper lobe of the 79 consecutive cases. The panel grading method showed more severe emphysema in the upper lobe than in the lower lobe to a panel score of 40; after this, the severity of emphysema in the two lobes was similar. Scores made from the Ryder grid were very similar to those made from the panel. Grading emphysema from one lobe, particularly the lower lobe, is not appropriate if precise clinicopathologic correlations are required.
Intracellular Protein Catabolism and its Control During Nutrient Deprivation and Supply
Authors: Glenn E. Mortimore, A. Reeta Pösö
Journal: Annual Review of Nutrition (1987)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Multiple Epstein-Barr virus-associated subcutaneous angioleiomyomas in a patient with acquired immunodeficiency syndrome
Authors: J.Y-F. Chang, C-S. Wang, C-C. Hung, T-F. Tsai, C-H. Hsiao
Journal: British Journal of Dermatology (2002)

Tumours of smooth muscle origin, either solitary or multiple, are occasionally found in immunocompromised patients, particularly in children with acquired immunodeficiency syndrome (AIDS). Most of the reported AIDS‐associated leiomyomatous neoplasms have been found in the visceral organs, and the tumour cells all possessed the Epstein–Barr virus (EBV) genome. Here we present a 32‐year‐old‐man with AIDS who developed three skin nodules on his lower left extremity. No other tumorous lesions were found using computed tomography scans. Two of the three nodules were resected for pathological examination. Histologically, both tumours were well circumscribed and located in the subcutis. The tumours were composed of interlacing fascicles of spindle‐shaped cells with prominent vasculature and lymphocytic infiltration. No pleomorphism, mitosis or necrosis was seen. Immunohistochemically, the tumour cells were reactive to smooth muscle actin and desmin. Angioleiomyoma was diagnosed. EBV‐encoded small RNAs were also demonstrated in the nucleus of the tumour cells by in situ hybridization but no EBV receptor (CD21) or latent membrane protein (LMP)‐1 was found in the tumour cells. No human herpesvirus (HHV)‐8 genome was detected in the lesion using polymerase chain reaction analysis. The results of this study indicated that EBV containing subcutaneous angioleiomyoma was another neoplasm that must be considered in patients with human immunodeficiency virus infection who develop skin nodules. The role of EBV in the pathogenesis of this unique neoplasm is still unknown.
Prevention of pain on injection of propofol: systematic review and meta-analysis
Authors: L. Jalota, V. Kalira, E. George, Y.-Y. Shi, C. Hornuss, O. Radke, N. L. Pace, C. C. Apfel
Journal: BMJ (2011)

<b>Objective</b> To systematically determine the most efficacious approach for preventing pain on injection of propofol. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> PubMed, Embase, Cochrane Library, www.clinicaltrials.gov, and hand searching from the reference lists of identified papers. <b>Study selection</b> Randomised controlled trials comparing drug and non-drug interventions with placebo or another intervention to alleviate pain on injection of propofol in adults. <b>Results</b> Data were analysed from 177 randomised controlled trials totalling 25 260 adults. The overall risk of pain from propofol injection alone was about 60%. Using an antecubital vein instead of a hand vein was the most effective single intervention (relative risk 0.14, 95% confidence interval 0.07 to 0.30). Pretreatment using lidocaine (lignocaine) in conjunction with venous occlusion was similarly effective (0.29, 0.22 to 0.38). Other effective interventions were a lidocaine-propofol admixture (0.40, 0.33 to 0.48); pretreatment with lidocaine (0.47, 0.40 to 0.56), opioids (0.49, 0.41 to 0.59), ketamine (0.52, 0.46 to 0.57), or non-steroidal anti-inflammatory drugs (0.67, 0.49 to 0.91); and propofol emulsions containing medium and long chain triglycerides (0.75, 0.67 to 0.84). Statistical testing of indirect comparisons showed that use of the antecubital vein and pretreatment using lidocaine along with venous occlusion to be more efficacious than the other interventions. <b>Conclusions</b> The two most efficacious interventions to reduce pain on injection of propofol were use of the antecubital vein, or pretreatment using lidocaine in conjunction with venous occlusion when the hand vein was chosen. Under the assumption of independent efficacy a third practical alternative could be pretreatment of the hand vein with lidocaine or ketamine and use of a propofol emulsion containing medium and long chain triglycerides. Although not the most effective intervention on its own, a small dose of opioids before induction halved the risk of pain from the injection and thus can generally be recommended unless contraindicated.
Role of Myeloid-Derived Suppressor Cells in Glucocorticoid-Mediated Amelioration of FSGS
Authors: Limin Li, Tao Zhang, Wenli Diao, Fangfang Jin, Lei Shi, Jiao Meng, Huan Liu, Jing Zhang, Cai-Hong Zeng, Ming-Chao Zhang, Shaoshan Liang, Yuan Liu, Chen-Yu Zhang, Zhihong Liu, Ke Zen
Journal: Journal of the American Society of Nephrology (2015)

The mechanism by which glucocorticoids alleviate renal inflammatory disorders remains incompletely understood. Here, we report that the efficacy of glucocorticoids in ameliorating FSGS depends on the capacity to expand myeloid-derived suppressor cells (MDSCs). After glucocorticoid treatment, the frequency of CD11b(+)HLA-DR(-)CD14(-)CD15(+) MDSCs in peripheral blood rapidly increased in patients with glucocorticoid-sensitive FSGS but remained unchanged in patients with glucocorticoid-resistant FSGS. The frequency of CD11b(+)Gr-1(+) MDSCs in mouse peripheral blood, bone marrow, spleen, kidney-draining lymph nodes (KDLNs), and kidney also increased after glucocorticoid treatment. The induced MDSCs from glucocorticoid-treated mice strongly suppressed T cells, dendritic cells, and macrophages but induced regulatory T cells in spleen, KDLNs, and kidney. Moreover, glucocorticoid treatment suppressed doxorubicin-induced T cell proliferation, dendritic cell and macrophage infiltration, and proinflammatory cytokine production, whereas this protective effect was largely abolished by depleting MDSCs using anti-Gr-1 antibody. Finally, the adoptive transfer of induced MDSCs into the doxorubicin-treated mice not only confirmed the protective role of MDSCs in doxorubicin-induced renal injury but also showed that the transferred MDSCs rapidly migrated into the lymphocyte-accumulating organs, such as the spleen and KDLNs, where they suppressed T cell proliferation. Taken together, these results demonstrate that glucocorticoid treatment ameliorates FSGS by expanding functional MDSCs and that this rapid elevation of MDSCs in peripheral blood may serve as an indicator for predicting the efficacy of glucocorticoid treatment.
Early separation of B and T lymphocyte precursors in chick embryo.
Authors: E Houssaint, A Mansikka, O Vainio
Journal: The Journal of Experimental Medicine (1991)

Embryonic chimeras were used to demonstrate an early separation of chicken T and B cell precursors. Genetically polymorphic cell surface antigens, Bu-1 and Ov, which are expressed on cells of the B and T lineage, respectively, are useful markers in adoptive cell transfer studies. Allelic products Bu-1a and Bu-1b can be detected with monoclonal antibodies (mAbs) L22 and 11G2, respectively, and the Ov antigen with mAb 11A9. Chimeric chickens were constructed by reconstituting irradiated 14-d Ov- H.B19 embryos with the sorted Bu-1+ or Bu-1- fractions of spleen cells from age-matched H.B19 Ov+ embryos. Chimeras were analyzed, 3-4 wk after hatching, for the presence of Ov+ cells in the bursa, thymus, spleen, and peripheral blood lymphocytes. T cell precursors giving rise to thymocytes and peripheral T cells were present only in the Bu-1-, but not in the Bu-1+, fraction. We previously demonstrated that, in contrast, all B cell precursors in spleen from 14-d embryos are exclusively present in the Bu-1+ fraction. We also analyzed the immunoglobulin light chain gene rearrangement in these populations by polymerase chain reaction. We show here that VJ recombination occurs in the Bu-1+, but not in the Bu-1-, fraction of spleen. These data demonstrate an early commitment to the B cell lineage, which occurs before the colonization of the bursa of Fabricius. Segregation of B cell precursors from the other hemopoietic precursors, and consequently separation of T and B cell precursors, occurs before the colonization of the primary lymphoid organs.
THE COLON AND COLITIS
Authors: T. G. Garry
Journal: BMJ (1921)

A LMzw Njs I. z)cALim A Ivy M., aged 12, was seen on September 19th with well- inarke(d niodes on both shins and a sore throat.TlThe nodes later also appeared on the extensor aspect of the arms and Joint pains were present.Ier attackwas much less severe, and she was well in about a fortnight.Phyllis M., aged 17, also developed the disease; she was seen first on October 3rd.The crop uf nodes was conifined to the shins, anid she complained of sore throat.Her attack was less severe thasn in the other two cases, the period of illness being about a fortniiglht.The point is that all tlhse cases are muembers of the same family.They were all girls.Eaclh complained of sore thlroat, and it is interesting to note that each succeeding case was less severe than its predecessor.Thle motlher, at the time of tlhe occurrence of the second case, volunteered the statement that her son, aged 20, had had similar '; spots " before May M. was taken ill, buit he was not compelled to seelk medical advice.-AWeare, etc.,
<i>TKTL1</i> Is Activated by Promoter Hypomethylation and Contributes to Head and Neck Squamous Cell Carcinoma Carcinogenesis through Increased Aerobic Glycolysis and HIF1α Stabilization
Authors: Wenyue Sun, Yan Liu, Chad A. Glazer, Chunbo Shao, Sheetal Bhan, Semra Demokan, Ming Zhao, Michelle A. Rudek, Patrick K. Ha, Joseph A. Califano
Journal: Clinical Cancer Research (2010)

This study aims to investigate the role of the aberrant expression of Transkelolase-like 1 (TKTL1) in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and to characterize TKTL1 contribution to HNSCC tumorigenesis through aerobic glycolysis and HIF1alpha stabilization.TKTL1 promoter hypomethylation and mRNA/protein aberrant expression were studied in human HNSCC tumor samples and normal mucosas. Oncogenic functions of TKTL1 were examined in HNSCC cell line panels and tumor xenograft models with TKTL1 expression construct. The metabolite levels of fructose-6-phosphate, glyceraldehydes-3-phosphate, pyruvate, lactate, and the levels of HIF1alpha protein and its downsteam glycolytic targets were compared between the TKTL1-expressing and vehicle-expressing HNSCC cells. Meanwhile, the effects of HIF1alpha/glycolytic inhibitors were evaluated on the TKTL1 transfectants.TKTL1 exhibits high frequency of promoter hypomethylation in HNSCC tumors compared with the normal mucosas, correlating with its overexpression in HNSCC. Overexpression of TKTL1 in HNSCC cells promoted cellular proliferation and enhanced tumor growth in vitro and in vivo. Overexpression of TKTL1 increased the production of fructose-6-phosphate and glyceraldehyde-3-phosphate, in turn elevating the production of pyruvate and lactate, resulting in the normoxic stabilization of the malignancy-promoting transcription factor HIF1alpha and the upregulation of downstream glycolytic enzymes. Notably, the reduction of TKTL1 expression decreased HIF1alpha accumulation and inhibition with HIF1alpha and/or the glycolysis inhibitor could abrogate the growth effects mediated by TKTL1 overexpression.TKTL1 is a novel candidate oncogene that is epigenetically activated by aberrant hypomethlation and contributes to a malignant phenotype through altered glycolytic metabolism and HIF1alpha accumulation.
OBSERVATIONS ON MIXTURES OF ELEMENTARY BODIES OF VACCINIA AND COATED COLLODION PARTICLES BY MEANS OF ULTRACENTRIFUGATION AND ELECTROPHORESIS
Authors: J. E. Smadel, E. G. Pickels, T. Shedlovsky, T. M. Rivers
Journal: The Journal of Experimental Medicine (1940)

It has been shown experimentally that mixtures of two types of particles, namely, elementary bodies of vaccinia and collodion particles coated with protein, sediment with a single boundary in the analytical centrifuge. Such mixtures have been shown to develop one or two boundaries on electrophoresis in the Tiselius apparatus, depending on the type of coating on the surface of the collodion particles. When covered with the heat-stable soluble antigen of vaccinia, collodion particles migrate in the electrical field at the same rate as elementary bodies. On the other hand, if they are coated with a component of normal rabbit serum, they migrate at a different rate. The estimation of purity of preparations of virus by means of data obtained by ultracentrifugation and electrophoresis is discussed.
Metabolism and toxicity of 2,2,2-trifluoroethyl vinyl ether.
Authors: V Fiserova-Bergerova
Journal: Environmental Health Perspectives (1977)

A review on metabolism and toxicity of the fluorinated anesthetic agent, fluroxene, is presented. Fluroxene anesthesia is nontoxic to man but fatal to many experimental animals. The fluroxene molecule (2,2,2-trifluroethyl vinyl ether) is composed of two moieties; both are toxic as a result of their metabolism: the vinyl moiety destroys heme of cytochrome P-450 while being metabolized to the final product, CO2. The trifluoroethyl moiety is oxidized to trifluoroethanol (TFE) and trifluoroacetic acid (TFAA), and the acute toxicity of fluroxene is related to this pathway. The ratio of metabolities (TFAA to TFE) excreted by different species exposed to fluroxene varies; whenever highly toxic TFE is the major metabolite, fluroxene toxicity is high (rodents, dogs, phenobarbital pretreated monkeys), whenever TFAA is the major metabolite (man, monkey) fluroxene is not toxic. Toxicity in different species also correlates with the extent of glutathione depletion following fluroxene exposure. Fluroxene metabolism and toxicity are modified by drugs metabolized by or affecting the activity of the microsomal cytochrome P-450-system or enzymes involved in ethanol metabolism. The susceptibility of fluroxene to two enzymatic systems which are modified by environmental and genetic factors may explain the large differences in fluroxene toxicity to various species. The fate of one-third of fluroxene administered to man remains unknown.
The Role of Hypoxia-Inducible Factor-1 in Three-dimensional Tumor Growth, Apoptosis, and Regulation by the Insulin-Signaling Pathway
Authors: Russell D. Leek, Ian Stratford, Adrian L. Harris
Journal: Cancer Research (2005)

The purpose of this study was to establish the effect of hypoxia-inducible factor-1 (HIF-1) directly on tumor growth, independently of angiogenesis. This was done by growing wild-type mouse hepatoma cells (HEPA-1) and their HIF-1-deficient counterpart C4 as multicellular tumor spheroids and quantifying differences in growth rates and proliferative and apoptotic indices. Insulin and insulin-like growth factor-I are key growth factors, also able to regulate hypoxia-responsive genes via HIF-1; thus, the effects of insulin on this model were also investigated. Two-dimensional growth was serum dependent and no difference was seen between wild-type HEPA-1 and C4 cell growth profiles, but major differences were seen in three-dimensional growth. HIF-1 supported spheroid growth under hypoxia as the HEPA-1 spheroids grew faster than the C4. Surprisingly, the HIF-1-deficient cells had a higher proliferation rate in three-dimensional growth (C4 mean S-phase index, 13.6%; HEPA-1 mean S-phase index, 9%; P = 0.009) that was associated with an inhibition of apoptosis. However, the apoptosis rate was much greater in these spheroids (C4 mean apoptotic index, 6.4; HEPA-1 mean apoptotic index, 0.78%; P = 0.0006). Addition of insulin increased proliferation and apoptosis in both HEPA-1 and C4 spheroids, demonstrating an HIF-1-independent effect of insulin signaling in three-dimensional growth. These results indicate that the enhancing effect of HIF-1 in three-dimensional tumor growth is a balance of both reduced proliferation and enhanced survival, the latter being proportionally greater.
Motivational styles in everyday life: a guide to reversal theory.
Authors: A Klarica
Journal: British Journal of Sports Medicine (2002)

I feel that this book is targeted towards academics, researchers, and people interested in motivation psychology generally, particularly reversal theory. As outlined in the preface and introductory chapter, reversal theory is a broad psychological theory which has received little attention from mainstream psychology. It specifically explores motivation, emotion, and personality.

The book is clearly a comprehensive overview of the research and application of reversal theory …
Phase I-II study of ADXS31-142 alone and in combination with pembrolizumab in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC): the KEYNOTE-046 trial
Authors: Naomi B Haas, Mark N Stein, Ronald Tutrone, Rodolfo Perini, Andrew Denker, David Mauro, Lawrence Fong
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Activation of tumor antigen-specific T-cell responses and bypass/neutralization of tumor immune tolerance mechanisms are essential for immunotherapeutic efficacy. Listeria monocytogenes ( Lm) -listeriolysin O (LLO) immunotherapies have shown to both generate antigen-specific T-
A memorable patient: The scars of the Jewish holocaust
Authors: R. Peleg
Journal: BMJ (2000)

Lamont have begun to help tease out the factors involved in end of life predictions.In oncology, the end of chemotherapy usually signals the terminal phase.In other specialties, prognosis is much less demarcated.Doctors should better define landmarks or turning points in prognosis and begin to acknowledge these to ourselves and to our patients.Only then can we adequately guide our patients through the dying process.
Genetic study of lymphoma induction by AKR mink cell focus-inducing virus in AKR x NFS crosses.
Authors: M W Cloyd, J W Hartley, W P Rowe
Journal: The Journal of Experimental Medicine (1981)

The mink cell focus-inducing (MCF)-247 virus, originally isolated from an AKR thymoma, is lymphomagenic in AKR mice but not in the ecotropic virus-negative NFS mouse strain. Analysis of sensitivity to lymphoma-induction by AKR-247 MCF virus in genetic hybrids between these two strains showed that F1 mice inoculated as sucklings were uniformly sensitive, whereas those inoculated as weanlings were generally resistant. In NFS backcross mice inoculated as sucklings, inheritance and expression of endogenous ecotropic virus from AKR was an essential correlate of replication of MCF virus and subsequent development of lymphoma. However, one-third of the mice expressing ecotropic virus and replicating the inoculated MCF virus did not develop lymphoma. The results suggested that an additional gene that influenced development of lymphoma may be involved, and that mice inheriting both virus-inducing loci from AKR were more susceptible than those inheriting only one. These findings indicate that the causal role of ecotropic virus infection in spontaneous thymomagenesis in AKR mice involves not only the generation of leukemogenic MCF viruses but also the establishment of permissiveness for their growth.
In situ chondrogenic differentiation of human adipose tissue-derived stem cells in a TGF-β1 loaded fibrin–poly(lactide-caprolactone) nanoparticulate complex
Authors: Youngmee Jung, Yong-Il Chung, Sang Hee Kim, Giyoong Tae, Young Ha Kim, Jong Won Rhie, Sang-Heon Kim, Soo Hyun Kim
Journal: Biomaterials (2009)
A phase II study of a novel gemcitabine plus cisplatin regimen administered every three weeks for advanced non-small-cell lung cancer
Authors: D. Castellano, P. Lianes, L. Paz-Ares, M. Hidalgo, J.A. Guerra, C. Gómez-Martín, H. Gómez, J. Calzas, H. Cortés-Funes
Journal: Annals of Oncology (1998)