RhoC is essential for TGF-β1-induced invasive capacity of rat ascites hepatoma cells

International Nuclear Information System (INIS)

Mukai, M.; Endo, H.; Iwasaki, T.; Tatsuta, M.; Togawa, A.; Nakamura, H.; Inoue, M.

2006-01-01

Transforming growth factor-β1 (TGF-β1) is a multifunctional growth factor that plays a role in cell proliferation, differentiation, extracellular matrix production, apoptosis, and cell motility. We show here that TGF-β1 increased the invasiveness of MM1 cells, which are a highly invasive clone of rat ascites hepatoma cells. Both mRNA and protein levels of RhoC but not RhoA in TGF-β1-treated MM1 cells increased. In parallel with this increase in expression, RhoC activity was induced by TGF-β1 treatment. When RhoC was overexpressed in MM1 cells, the invasive capacity increased. The RhoC-overexpressing cells formed more nodules than did mock cells when injected into rat peritoneum. Furthermore, when RhoC expression was reduced by transfection with shRNA/RhoC, the invasiveness of MM1 cells decreased with concomitant suppression of RhoC expression. Thus, the induced expression of RhoC by TGF-β1 in MM1 cells plays a critical role in TGF-β1-induced cell migration

Up-regulation of ALG-2 in hepatomas and lung cancer tissue

DEFF Research Database (Denmark)

la Cour, Jonas Marstrand; Mollerup, Jens; Winding, Pernille

2003-01-01

, a result confirmed by immunohistochemical analysis. Staining of four different lung cancer tissue microarrays including specimens of 263 patients showed that ALG-2 is mainly localized to epithelial cells and significantly up-regulated in small-cell lung cancers and in non-small-cell lung cancers. Our...... using Western blot analysis and immunohistochemistry. Western blot analysis of 15 different adult mouse tissues demonstrated that ALG-2 is ubiquitously expressed. We found that ALG-2 was more than threefold overexpressed in rat liver hepatoma compared to normal rat liver using Western blot analysis...

Desensitization of γ-aminobutyric acid receptor from rat brain: two distinguishable receptors on the same membrane

International Nuclear Information System (INIS)

Cash, D.J.; Subbarao, K.

1987-01-01

Transmembrane chloride flux mediated by γ-aminobutyric acid (GABA) receptor can be measured with a mammalian brain homogenate preparation containing sealed membrane vesicles. The preparation can be mixed rapidly with solutions of defined composition. Influx of 36 Cl - tracer initiated by mixing with GABA was rapidly terminated by mixing with bicuculline methiodide. The decrease in the isotope influx measurement due to prior incubation of the vesicle preparation with GABA, which increased with preincubation time and GABA concentration, was attributed to desensitization of the GABA receptor. By varying the time of preincubation with GABA between 10 ms and 50 s with quench-flow technique, the desensitization rates could be measured over their whole time course independently of the chloride ion flux rate. Most of the receptor activity decreased in a fast phase of desensitization complete in 200 ms at saturation with GABA. Remaining activity was desensitized in a few seconds. These two phases of desensitization were each kinetically first order and were shown to correspond with two distinguishable GABA receptors on the same membrane. The receptor activities could be estimated, and the faster desensitizing receptor was the predominant one, giving on average ca. 80% of the total activity. The half-response concentrations were similar, 150 and 114 μM for the major and minor receptors, respectively. The dependence on GABA concentration indicated that desensitization is mediated by two GABA binding sites. The fast desensitization rate was approximately 20-fold faster than previously reported rates while the slower desensitization rate was slightly faster than previously reported rates

Experimental study on 131I-labelled anti-alpha-fetoprotein antibodies in the diagnosis of rat hepatoma

International Nuclear Information System (INIS)

Terashima, Hiromi

1980-01-01

The tumor-specificity of 131 I-labelled anti-α-fetoprotein antibodies was evaluated in rats using α-fetoprotein-producing AH66C4 rat hepatoma as a model. 1) Following the 12 hour incubation of 125 I-labelled anti-α-fetoprotein antibodies and tumor cells, microautoradiography revealed marked radioactivity in and around the tumor cells. This suggested that the labelled antibodies accumulated around the cells and were combined with the α-fetoprotein secreted from the cells. 2) The tumor was transplanted subcutaneously into the thighs of rats. There was marked accumulation of 131 I-antibodies in the tumor with cyst formation, but there was none in the tumor without cyst formation. The accumulation was enhanced by the administration of non-labelled antibodies to the rats before the administration of 131 I-antibodies. The α-fetoprotein level was higher in the cyst than in any other organ. 131 I-labelled horse-γ-globulins administered as a control, also accumulated in the tumor with cyst but the degree of accumulation did not exceed that of the 131 I-antibodies. The amount of 131 I-antibodies accumulated increased, while that of 131 I-horse-γ-globulins decreased with time. This indicated that the accumulation of the γ-globulins in the tumor was nonspecific and that it was related to the blood pool. These results strongly suggest that the accumulation of 131 I-antibodies in the tumor with cyst formation was a specific antigen-antibody reaction, and the present procedure reported is applicable in the specific diagnosis of such kinds of α-fetoprotein secreting tumor. (author)

Basil extract inhibits the sulfotransferase mediated formation of DNA adducts of the procarcinogen 1'-hydroxyestragole by rat and human liver S9 homogenates and in HepG2 human hepatoma cells

NARCIS (Netherlands)

Jeurissen, S.M.F.; Punt, A.; Delatour, T.; Rietjens, I.M.C.M.

2008-01-01

The effects of a basil extract on the sulfation and concomitant DNA adduct formation of the proximate carcinogen 1¿-hydroxyestragole were studied using rat and human liver S9 homogenates and the human hepatoma cell line HepG2. Basil was chosen since it contains the procarcinogen estragole that can

Radiation-induced cell disintegrations in cultured rat hepatoma cells JTC 2

International Nuclear Information System (INIS)

Sakka, Masatoshi

1979-01-01

Disintegration of hepatoma cells of rat were recorded by time lapse cinemicrography for more than 5 days and about 1000 pedigrees were analyzed. Five generations were followed up in control and 2 or 3 generations in irradiated cells. Cells were attached on vessel wall spreading themselves in intermitotic phase while they stood up from the wall in mitotic phase taking a roun form. When a cell disintegrates in interphase the disintegration is called D sub( s) and one in mitotic period D sub( r). The frequency of D sub( s)S' is about 3 times as much as D sub( r)S'. An age of a disintegrated cell in generation 1 and 2 was measured as the previous mitosis was age 0. Generation times of the comparable generations of surviving sister branches of the same pedigrees were used as controls. Most disintegration took place at the same age with surviving sisters indicating a determined, not at random, age of cell death. A cell in an initial state flowed to any one of the following states with or without irradiation; surviving, disintegrated, end cell or escaping out of observation field. A single exposure of 400 to 900 R induced a typical reproductive death but effective extinction of clones was observed only in small pedigrees. Temporary hypothermia and hyperthermia immediately after exposure had no remarkable lethal effects on several early generations. (author)

Basil extract inhibits the sulfotransferase mediated formation of DNA adducts of the procarcinogen 1′-hydroxyestragole by rat and human liver S9 homogenates and in HepG2 human hepatoma cells

NARCIS (Netherlands)

Jeurissen, S.M.F.; Punt, A.; Delatour, T.; Rietjens, I.M.C.M.

2008-01-01

The effects of a basil extract on the sulfation and concomitant DNA adduct formation of the proximate carcinogen 1′-hydroxyestragole were studied using rat and human liver S9 homogenates and the human hepatoma cell line HepG2. Basil was chosen since it contains the procarcinogen estragole that can

Active, Passive, and Vicarious Desensitization

Science.gov (United States)

Denney, Douglas R.

1974-01-01

Two variations of desensitization therapy for reducing test anxiety were studied, active desensitization in which the client describes his visualizations of the scenes and vicarious desensitization in which the client merely observes the desensitization treatment of another test anxious client. The relaxation treatment which emphasized application…

Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats.

Science.gov (United States)

Rezvani, Amir H; Cauley, Marty; Xiao, Yingxian; Kellar, Kenneth J; Levin, Edward D

2013-03-01

Nicotine and nicotinic agonists have been shown to improve attentional function. Nicotinic receptors are easily desensitized, and all nicotinic agonists are also desensitizing agents. Although both receptor activation and desensitization are components of the mechanism that mediates the overall effects of nicotinic agonists, it is not clear how each of the two opposed actions contributes to attentional improvements. Sazetidine-A has high binding affinity at α4β2 nicotinic receptors and causes a relatively brief activation followed by a long-lasting desensitization of the receptors. Acute administration of sazetidine-A has been shown to significantly improve attention by reversing impairments caused by the muscarinic cholinergic antagonist scopolamine and the NMDA glutamate antagonist dizocilpine. In the current study, we tested the effects of chronic subcutaneous infusion of sazetidine-A (0, 2, or 6 mg/kg/day) on attention in Sprague-Dawley rats. Furthermore, we investigated the effects of chronic sazetidine-A treatment on attentional impairment induced by an acute administration of 0.02 mg/kg scopolamine. During the first week period, the 6-mg/kg/day sazetidine-A dose significantly reversed the attentional impairment induced by scopolamine. During weeks 3 and 4, the scopolamine-induced impairment was no longer seen, but sazetidine-A (6 mg/kg/day) significantly improved attentional performance on its own. Chronic sazetidine-A also reduced response latency and response omissions. This study demonstrated that similar to its acute effects, chronic infusions of sazetidine-A improve attentional performance. The results indicate that the desensitization of α4β2 nicotinic receptors with some activation of these receptors may play an important role in improving effects of sazetidine-A on attention.

Degradation and repair of DNA from rat hepatoma cells after treatments with γ-rays and N-methyl-N-nitrosourea

International Nuclear Information System (INIS)

Zakrzhevskaya, D.G.; Kulagina, T.P.; Petrov, S.I.; Fomenko, L.A.; Gaziev, A.I.

1977-01-01

It has been shown, that DNA single-strand breaks induced in the cells of ascite hepatoma with γ-rays and metylnitrosourea (MNM) are effectively repaired. DNA two-strand breaks of hepatoma cells, treated with MNM are effectively repaired in situ as well. Only insignificant part of two-strand gamma-induced breaks in DNA of these cells is repaired during postirradiation period. Under combined effect of gamma rays and MNM on hepatoma cells a delay of DNA reparation and its further degradation as well as inhibition of nonplanned DNA synthesis and the suppression of DNA-polymerase 1 activity are observed

Insulin regulation of Na/K pump activity in rat hepatoma cells

International Nuclear Information System (INIS)

Gelehrter, T.D.; Shreve, P.D.; Dilworth, V.M.

1984-01-01

Insulin rapidly increases Na/K pump activity in HTC rat hepatoma cells in tissue culture, as measured by the ouabain-sensitive influx of the potassium analogue 86Rb+. Increased influx is observed within minutes and is maximal (70% above control) within 1-2 h. The effect appears to be mediated by the insulin receptors, as: the concentration dependence on insulin is identical to that for insulin induction of tyrosine aminotransferase and stimulation of 2-aminoisobutyric acid transport, proinsulin is 6% as potent as insulin, and the effect is blocked by anti-receptor antibodies. The early stimulation of potassium influx is not blocked by cycloheximide and is not associated with an increased number of pump sites as measured by 3 H-ouabain binding. The insulin effect is blocked by amiloride, which blocks sodium influx, and is mimicked by the sodium ionophore monensin, which increases sodium influx and intracellular accumulation. Insulin also rapidly increases the initial rate of 22 Na+ influx, suggesting that insulin may enhance Na/K pump activity, in part, by increasing intracellular sodium concentration. Incubation of HTC cells with insulin for 24 h causes complete unresponsiveness to the insulin induction of transaminase and stimulation of amino acid transport, a phenomenon mediated by postbinding mechanisms. In contrast, similar incubation with insulin does not cause unresponsiveness to the insulin stimulation of Na/K pump activity. Therefore, the site of regulation of responsiveness to insulin must be distal to, or separate from, those events causing stimulation of ion fluxes

Rapid internalization of the insulin receptor in rat hepatoma cells

International Nuclear Information System (INIS)

Backer, J.M.; White, M.F.; Kahn, C.R.

1987-01-01

The authors have studied the internalization of the insulin receptor (IR) in rat hepatoma cells (Fao). The cells were surface-iodinated at 4 0 C, stimulated with insulin at 37 0 C, and then cooled rapidly, trypsinized at 4 0 C and solubilized. The IR was immunoprecipitated with a specific antibody, and internalization of the IR was assessed by the appearance of trypsin-resistant bands on SDS-PAGE. Insulin induced the internalization of surface receptors with a t 1/2 of 9-10 mins; cells not exposed to insulin internalized less than 20% of the IR during 1 h at 37 0 C. Further experiments demonstrated that the accumulation of trypsin-resistant IR paralleled a loss of receptor from the cell surface. Insulin-stimulated cells were chilled and iodinated at 4 0 C, followed by solubilization, immunoprecipitation and SDS-PAGE; alternatively, insulin-stimulated cells were chilled, surface-bound ligand removed by washing the cells at pH 4.2, and specific [ 125 I]insulin binding measured at 4 0 C. Both techniques confirmed the disappearance of IR from the cell surface at rates comparable to the insulin-stimulated internalization described above. The total amount of phosphotyrosine-containing IR, as assessed by immunoprecipitation with an anti-phosphotyrosine antibody, remained constant during this time interval, suggesting that active kinase is translocated into the cell. In summary, the authors data indicate that insulin binding increases the rate of IR internalization of Fao cells. This relocation may facilitate the interaction of the activated tyrosine kinase in the IR with intracellular substrates, thus transmitting the insulin signal to metabolic pathways

Desensitization to rituximab in a multidisciplinary setting.

Science.gov (United States)

Amorós-Reboredo, Patrícia; Sánchez-López, Jaime; Bastida-Fernández, Carla; do Pazo-Oubiña, Fernando; Borràs-Maixenchs, Núria; Giné, Eva; Valero, Antonio; Creus-Baró, Natàlia

2015-10-01

The need to offer first-line therapy to the increasing number of patients who have suffered an hypersensitivity reaction has stimulated the use of rapid desensitization protocols. To present our experience working as a multidisciplinary team using a rituximab rapid desensitization scheme. Patient demographics, allergic reaction, skin tests to rituximab, number of desensitizations, reactions during the desensitization protocol and actions taken, number of administered and completed cycles, were retrospectively collected in patients who received at least one desensitization to rituximab. Number of desensitizations successfully managed. Between 2012 and June 2013 five patients received a total of 19 desensitizations to rituximab using a 12 step rapid desensitization protocol. All patients received the scheduled chemotherapeutic cycles as inpatients, with no delay in administration dates. Three patients presented a hypersensitivity reaction during the first desensitization and in one patient the event occurred again during the second treatment cycle. All reactions occurred in the last step, when the infusion rate reached the maximum speed. The developed protocol for rapid desensitization was successful in five patients receiving rituximab. Patients could receive the full intended dose.

In Vivo Desensitization: An Alternative to Systematic Desensitization with College Students

Science.gov (United States)

Atkinson, Donald R.

1973-01-01

It is the thesis of this article that college counselors would make more economical and efficacious use of their time and would greatly reduce the risk of turning off'' students if they employed in vivo desensitization rather than systematic desensitization when dealing with anxious clients. (Author)

Cytotoxicity of the dicarboximide fungicides, vinclozolin and iprodione, in rat hepatoma-derived Fa32 cells.

Science.gov (United States)

Dierickx, Paul J

2004-10-01

Dicarboximide fungicides are widely used to control various fungal species. Their primary action is not known, due to a lack of knowledge concerning the mechanism of action of the dicarboximide group. The cytotoxicities of vinclozolin and iprodione in rat hepatoma-derived Fa32 cells were investigated. Cytotoxicity was measured by neutral red uptake inhibition after treatment for 24 hours. Iprodione was more toxic than vinclozolin. Vinclozolin was less toxic in glutathione-depleted cells than in control cells. This was also true for iprodione at lower concentrations, but iprodione became more toxic at higher concentrations. Both the fungicides increased the endogenous glutathione content by 20% after 1 hour. After 24 hours, the glutathione content was doubled by vinclozolin, but was not affected by iprodione. No effect on glutathione S-transferase activity or reactive oxygen species formation could be observed. Cytochrome P450-dependent ethoxyresorufin-O-deethylase and pentoxyresorufin-O-depentylase activities were moderately activated by iprodione and strongly activated by vinclozolin. A glutathione-related cytochrome P450-dependent metabolic attack of vinclozolin and iprodione could be responsible for their cytotoxicity in Fa32 cells. Further research is needed to fully elucidate these (or other) mechanisms.

The Possible Therapeutic Role of Polyphenyl Constituents in Turmeric and Tamoxifen on Hepatocellular Carcinoma Chemically Induced in Rats

International Nuclear Information System (INIS)

Abdelgawad, M.R.

2017-01-01

Tamoxifen is a drug wildly used for the adjuvant therapy in the treatment of women with estrogen receptor-positive breast tumors and has a low incidence of serious side-effects. Feeding turmeric ( Curcuma longa L .) to rats has no apparent side effects; reduced the types of inflammation that can cause liver cell damage, blockage and scarring. Turmeric delay the damage caused by progressive inflammatory liver disease. This study was carried out to study the possible therapeutic effect of polyphenyl constituents in turmeric and tamoxifen on hepatocarcinogenesis in rats chemically induced by diethylnitrosamine (DEN). Thirty five male rats were injected with DEN in a single dose i.p. (200mg/kg), 7 rats were sacrificed after ~6 months for histopathological examination for HCC nodules in different lobes and lobules, many nodules were observed by naked eye with a diameter of about ~2-3mm. The remaining 28 hepatoma (HCC) bearing rats chemically induced were randomized divided into 4 groups (each of 7rats): hepatoma bearing rats receiving the control diet; hepatoma bearing rats (supplemented with 4g/kg (wt/wt) turmeric (~200 μg curcumin /rat/day/4weeks; hepatoma bearing rats treated with 50mg/kg (wt/wt) tamoxifen dissolved in 0.1 ml dimethylsulfoxide and diluted with normal saline and drinking water; hepatoma bearing rats treated with 50mg/kg (wt/wt) tamoxifen in 0.1 ml dimethylsulfoxide and diluted with normal saline and drinking water and supplemented with 4g/ kg (wt/wt) turmeric(~200 μg curcumin /rat/day/4weeks; besides, 7 male rats serves as control group. By the end of the experiment at 4 weeks, rats in each group were sacrificed for examination.

Systematic Desensitization and the Reduction of Anxiety.

Science.gov (United States)

Deffenbacher, Jerry L.; Suinn, Richard M.

1988-01-01

Provides detailed information on systematic desensitization, describing in detail the procedures of imaginal desensitization. Briefly describes variants of group, in vivo, massed, and self-administered desensitization. Outlines guidelines for appropriate selection and use of desensitization and presents sampling of research findings with diversity…

Choline evokes fluid secretion by perfused rat mandibular gland without desensitization

DEFF Research Database (Denmark)

Murakami, M; Novak, I; Young, J A

1986-01-01

M and evoked secretory responses comparable with those of acetylcholine (0.05-1.0 microM) administered at similar Na concentrations. Continuous infusion of choline, in contrast to acetylcholine, did not lead to a fall off in the secretory response (desensitization or tachyphylaxis) until the choline...

Effectiveness of oxaliplatin desensitization protocols.

Science.gov (United States)

Cortijo-Cascajares, Susana; Nacle-López, Inmaculada; García-Escobar, Ignacio; Aguilella-Vizcaíno, María José; Herreros-de-Tejada, Alberto; Cortés-Funes Castro, Hernán; Calleja-Hernández, Miguel-Ángel

2013-03-01

Hypersensitivity reaction (HSR) to antineoplastic drugs can force doctors to stop treatment and seek other alternatives. These alternatives may be less effective, not as well tolerated and/or more expensive. Another option is to use desensitization protocols that induce a temporary state of tolerance by gradually administering small quantities of the antineoplastic drug until the therapeutic dosage is reached. The aim of this study is to assess the effectiveness of oxaliplatin desensitization protocols. A retrospective observational study was carried out between January 2006 and May 2011. The inclusion criteria were patients undergoing chemotherapy treatment with oxaliplatin who had developed an HSR to the drug and who were candidates for continuing the treatment using a desensitization protocol. The patients' clinical records were reviewed and variables were gathered relating to the patient, the treatment, the HSR, and the desensitization protocol administered. The data were analysed using version 18.0 of the statistics program SPSS. A total of 53 desensitization protocols were administered to 21 patients. In 89 % of these cases, no new reactions occurred while the drug was being administered. New reactions of mild severity only occurred in 11 % of cases, and none of these reactions were severe enough for treatment to be stopped. All patients were able to complete the desensitization protocol. This study confirms that oxaliplatin desensitization protocols are safe and effective and allow patients to continue with the treatment that initially caused an HSR.

Estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the hypothalamus is independent of estrogen receptor-beta.

Science.gov (United States)

Rossi, Dania V; Dai, Ying; Thomas, Peter; Carrasco, Gonzalo A; DonCarlos, Lydia L; Muma, Nancy A; Li, Qian

2010-08-01

Estradiol regulates serotonin 1A (5-HT(1A)) receptor signaling. Since desensitization of 5-HT(1A) receptors may be an underlying mechanism by which selective serotonin reuptake inhibitors (SSRIs) mediate their therapeutic effects and combining estradiol with SSRIs enhances the efficacy of the SSRIs, it is important to determine which estrogen receptors are capable of desensitizating 5-HT(1A) receptor function. We previously demonstrated that selective activation of the estrogen receptor, GPR30, desensitizes 5-HT(1A) receptor signaling in rat hypothalamic paraventricular nucleus (PVN). However, since estrogen receptor-beta (ERbeta), is highly expressed in the PVN, we investigated the role of ERbeta in estradiol-induced desensitization of 5-HT(1A) receptor signaling. We first showed that a selective ERbeta agonist, diarylpropionitrile (DPN) has a 100-fold lower binding affinity than estradiol for GPR30. Administration of DPN did not desensitize 5-HT(1A) receptor signaling in rat PVN as demonstrated by agonist-stimulated hormone release. Second, we used a recombinant adenovirus containing ERbeta siRNAs to decrease ERbeta expression in the PVN. Reductions in ERbeta did not alter the estradiol-induced desensitization of 5-HT(1A) receptor signaling in oxytocin cells. In contrast, in animals with reduced ERbeta, estradiol administration, instead of producing desensitization, augmented the ACTH response to a 5-HT(1A) agonist. Combined with the results from the DPN treatment experiments, desensitization of 5-HT(1A) receptor signaling does not appear to be mediated by ERbeta in oxytocin cells, but that ERbeta, together with GPR30, may play a complex role in central regulation of 5-HT(1A)-mediated ACTH release. Determining the mechanisms by which estrogens induce desensitization may aid in the development of better treatments for mood disorders. Copyright 2010 Elsevier Ltd. All rights reserved.

Studies on Anti-Hepatoma Effect of Gan-Ai-Xiao Decoction

African Journals Online (AJOL)

Nowadays, the people's lifestyles such as obesity [1], smoking [2] and alcohol drinking [3] enhance the incidence of hepatoma. Hepatoma is the second leading cause of cancer mortality worldwide [4] and a number of therapies have been used to decrease the mortality of patients with hepatoma, such as surgical treatment ...

Aggravation of serum Hepatocyte Growth Factor levels during hepato carcinogenesis in Rats

International Nuclear Information System (INIS)

Abdelgawad, M.R.; Ghareeb, N.A.

2010-01-01

Hepatocyte growth factor (HGF) has an essential role during liver development and it plays an important role in the regeneration and repair of injured tissues and acting as a mitogen, motogen and morphogens for a variety of epithelial cells. The role of HGF in carcinogenesis is in straggle and so, the present study aimed to through light through the level of HGF during different steps of carcinogenesis. Forty male rats were given diethylnitrosamine (DEN) in drinking water (100 mg/l) for up to 16 weeks. Eight rats were sacrificed at 8, 12 and 16 weeks. Besides, 8 hepatoma bearing rats were exposed to a single dose gamma irradiation (3 Gy) were sacrificed after 2 weeks from exposure (2 rats died, 36 hrs post irradiation) and 8 hepatoma bearing rats were sacrificed after 4 weeks from receiving a combined antioxidant (N-acetylcysteine and Lmethionine). Serum HGF was assayed by enzyme linked immunosorbent assay (ELISA). Serum HGF level in DEN treated rats and in exposed hepatoma bearing rats was significantly higher than in control rats whereas, serum HGF level after treatment with N acetylcysteine and L-methionine for 4 weeks was significantly decreased than DEN treated rats and concluded that serum HGF may play a role during promotion and progression of hepatocellular carcinoma (HCC) and during treatment

Antibiotic Desensitization Therapy in Secondary Syphilis and Listeria Infection: Case Reports and Review of Desensitization Therapy

Science.gov (United States)

Magpantay, Gil; Madar, Cristian S; Hsue, Gunther; Belnap, Conrad

2011-01-01

Two adult cases, one of secondary syphilis and one of Listeria monocytogenes bacteremia, in which antibiotic desensitization therapy was utilized to assist treatment of active infection in the face of severe penicillin allergy. Clinical considerations are discussed that led to the decision to employ a formal desensitization procedure. Antibiotic desensitization protocols can facilitate optimal and safe antibiotic therapy in the appropriate clinical setting. PMID:22187514

Effect of focal irradiation on plasma kallikrein activity in tumor bearing rats

International Nuclear Information System (INIS)

Makoyo, P.O.Z.R.; West, W.L.

1977-01-01

The activated plasma kallikrein from tumor bearing rats before and after focal irradiation of the hind limbs was measured by the hydrolysis of 0.015M N-(p-toluene sulfonyl)-L arginine methyl ester (TAME). Blood was collected from abdominal aorta of rats anesthetized with diethyl ether into plastic tubes containing 1 volume of 3.8 percent sodium citrate for each 9 volumes. Plasma was isolated by centrifugation (2000 g) at 4 0 C. Small pieces of minced tumor tissue were inserted in a trochar and inoculated in the hind limbs of the rats. Morris hepatomas 7777 and 3924A were transplanted subcutaneously over the hind legs while Walker 256 tumor was transplanted intramuscularly in the hind limbs. Plasma kallikrein (μm TAME utilized/ml/hr) was decreased in three different groups of tumor bearing rats: Walker tumor from 207 +- 34 to 114 +- 30 Hepatoma 7777 from 219 +- 13 to 106 +- 3 and Hepatoma 3924A from 227 +- 7 to 133 +- 5. Two hours after focal irradiation (1000 R) plasma kallikrein decreased further in Walker tumor and hepatoma 7777 to 55 +- 5 and 96 +- 3.6 respectively. The plasma of tumor bearing rats becomes deficient in kallikrein at about the time metastases may be identified. The acute fall in plasma kallikrein is consistent with the overall stress mechanism

Variables affecting the tumor localization of 131I-antiferritin in experimental hepatoma

International Nuclear Information System (INIS)

Rostock, R.A.; Klein, J.L.; Kopher, K.A.; Order, S.E.

1984-01-01

Ferritin is both a normal tissue- and tumor-associated protein. The in vivo localization of 131 I-radiolabeled antitumor ferritin and normal IgG antibodies in the H-4-II-E rat hepatoma model was investigated in both tumor and normal tissues over a dose range of 0.67 micrograms to 5 mg of normal and antiferritin IgG and at labeling ratios (microCi 131 I per micrograms IgG) of 15:1, 5:1, and 1:10. The total dose from nonpenetrating radiation in rads was calculated and demonstrated a maximum of 2.9 times greater dose deposition (rads) of antiferritin than normal IgG in hepatoma without specific increase in binding in normal tissues. The maximum tumor targeting achieved was dependent on the amount of injected IgG and not on the labeling ratio or procedure. The binding in tumor could be inhibited by unlabeled antiferritin but not by unlabeled normal rabbit IgG and demonstrated the requirement of specificity for tumor binding. Normal tissues did not target with antiferritin. Most normal tissues have a capacity to bind normal and antiferritin IgG nonspecifically that is linear in relationship to the amount of injected IgG. The results demonstrate that 131 I-antiferritin selectively targets ferritin-secreting hepatoma over normal tissues and that the amount of targeting is dependent on the amount of antiferritin injected. The physiologic reasons for such selective localization is not known, but the term ''biologic window'' has been used to describe the differential availability of tumor ferritin for binding

Aspirin Allergy Desensitization in Cerebrovascular Disease

Science.gov (United States)

Zuckerman, Scott L; Seder, David B; Tsujiura, Crystiana; Cushing, Deborah; Gallup, Holly; Mocco, J; Hanel, Richard A; Ecker, Robert D

2014-01-01

Summary Aspirin (ASA) is the mainstay of treatment in cerebrovascular and systemic vascular disease. ASA hypersensitivity can pose a challenge to achieving optimum medical management prior to and after neurointerventional treatment. Desensitization to ASA is well described in the allergy and cardiovascular literature, but there are no similar discussions specific to neurointervention. The purpose of our study was to describe our experience with ASA hypersensitivity management and review the relevant literature. Two cases of patients with symptomatic cerebrovascular disease requiring neurointervention who were successfully desensitized to their ASA hypersensitivity prior to treatment are described. The subsequent literature is reviewed. Several ASA desensitization protocols exist and have been proven to successfully treat ASA hypersensitivity and allow for ASA therapy to be safely initiated. We describe several previously published protocols. ASA desensitization is a safe and simple way to manage ASA hypersensitivity. We provide comprehensive management guidelines for the neurointerventionalist engaging in ASA desensitization. PMID:24556294

Stimulation of Hepatoma Cell Invasiveness and Metastatic Potential by Proteins Secreted From Irradiated Nonparenchymal Cells

Energy Technology Data Exchange (ETDEWEB)

Zhou Leyuan [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai (China); Wang Zhiming [Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai (China); Gao Yabo [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai (China); Wang Lingyan [Experimental Research Center, Zhongshan Hospital, Fudan University, Shanghai (China); Zeng Zhaochong, E-mail: zeng.zhaochong@zs-hospital.sh.cn [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai (China)

2012-11-01

Purpose: To determine whether factors secreted by irradiated liver nonparenchymal cells (NPCs) may influence invasiveness and/or metastatic potential of hepatocellular carcinoma (HCC) cells and to elucidate a possible mechanism for such effect. Methods and Materials: Primary rat NPCs were cultured and divided into irradiated (10-Gy X-ray) and nonirradiated groups. Forty-eight hours after irradiation, conditioned medium from irradiated (SR) or nonirradiated (SnonR) cultures were collected and added to sublethally irradiated cultures of the hepatoma McA-RH7777 cell line. Then, hepatoma cells were continuously passaged for eight generations (RH10Gy-SR and RH10Gy-SnonR). The invasiveness and metastatic potential of McA-RH7777, RH10Gy-SnonR, and RH10Gy-SR cells were evaluated using an in vitro gelatinous protein (Matrigel) invasion and an in vivo metastasis assay. In addition, SR and SnonR were tested using rat cytokine antibody arrays and enzyme-linked immunosorbent assay (ELISA). Results: In vitro gelatinous protein invasion assay indicated that the numbers of invading cells was significantly higher in RH10Gy-SR (40 {+-} 4.74) than in RH10Gy-SnonR (30.6 {+-} 3.85) cells, and lowest in McA-RH7777 (11.4 {+-} 3.56) cells. The same pattern was observed in vivo in a lung metastasis assay, as evaluated by number of metastatic lung nodules seen with RH10Gy-SR (28.83 {+-} 5.38), RH10Gy-SnonR (22.17 {+-} 4.26), and McA-RH7777 (8.3 {+-} 3.8) cells. Rat cytokine antibody arrays and ELISA demonstrated that metastasis-promoting cytokines (tumor necrosis factor-{alpha} and interleukin-6), circulating growth factors (vascular endothelial growth factor and epidermal growth factor), and metalloproteinases (MMP-2 and MMP-9) were upregulated in SR compared with SnonR. Conclusions: Radiation can increase invasiveness and metastatic potential of sublethally irradiated hepatoma cells, and soluble mediators released from irradiated NPCs promote this potential. Increased secretion of

Systemic Chemical Desensitization of Peptidergic Sensory Neurons with Resiniferatoxin Inhibits Experimental Periodontitis

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Breivik, Torbjørn; Gundersen, Yngvar; Gjermo, Per; Fristad, Inge; Opstad, Per Kristian

2011-01-01

Background and objective: The immune system is an important player in the pathophysiology of periodontitis. The brain controls immune responses via neural and hormonal pathways, and brain-neuro-endocrine dysregulation may be a central determinant for pathogenesis. Our current knowledge also emphasizes the central role of sensory nerves. In line with this, we wanted to investigate how desensitization of peptidergic sensory neurons influences the progression of ligature-induced periodontitis, and, furthermore, how selected cytokine and stress hormone responses to Gram-negative bacterial lipopolysaccharide (LPS) stimulation are affected. Material and methods: Resiniferatoxin (RTX; 50 μg/kg) or vehicle was injected subcutaneously on days 1, 2, and 3 in stress high responding and periodontitis-susceptible Fischer 344 rats. Periodontitis was induced 2 days thereafter. Progression of the disease was assessed after the ligatures had been in place for 20 days. Two h before decapitation all rats received LPS (150 μg/kg i.p.) to induce a robust immune and stress response. Results: Desensitization with RTX significantly reduced bone loss as measured by digital X-rays. LPS provoked a significantly higher increase in serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α, but lower serum levels of the anti-inflammatory cytokine interleukin (IL)-10 and the stress hormone corticosterone. Conclusions: In this model RTX-induced chemical desensitization of sensory peptidergic neurons attenuated ligature-induced periodontitis and promoted a shift towards stronger pro-inflammatory cytokine and weaker stress hormone responses to LPS. The results may partly be explained by the attenuated transmission of immuno-inflammatory signals to the brain. In turn, this may weaken the anti-inflammatory brain-derived pathways. PMID:21339860

In Vitro Desensitization of Human Skin Mast Cells

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Zhao, Wei; Gomez, Gregorio; Macey, Matthew; Kepley, Christopher L.

2013-01-01

Desensitization is a clinical procedure whereby incremental doses of a drug are administered over several hours to a sensitive patient until a therapeutic dose and clinical tolerance are achieved. Clinical tolerance may occur in part by attenuating the mast cell response. In the present study, primary human skin mast cells were used to establish and characterize an in vitro model of desensitization. Mast cells in culture were armed with allergen-specific (4-hydroxy-3-nitro-phenylacety and Der p2) and non-specific IgE antibodies, and then desensitized by incremental exposures to 4-hydroxy-3-nitrophenylacety-BSA. This desensitization procedure abrogated the subsequent degranulation response to the desensitizing allergen, to an unrelated allergen, and to IgG anti-FcεRI, but not to C5a, substance P, compound 48/80, and calcium ionophore. Desensitized cells regained their FcεRI-dependent degranulation capability by 24–48 h after free allergen had been removed. Therefore, sensitized human skin mast cells are reversibly desensitized in vitro by exposure to incremental doses of that allergen, which also cross-desensitizes them to an unrelated allergen. PMID:22009002

Desensitization to Oxcarbazepine: Long-Term Efficacy and Tolerability

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Lee, Jiwon; Park, Eu Gene; Lee, Munhyang

2017-01-01

Background and Purpose Antiepileptic drug (AED)-associated cutaneous adverse drug reactions can lead to the discontinuation of medications. The aim of this study was to determine the long-term efficacy and safety of performing desensitization to oxcarbazepine. Methods This study involved 20 patients who exhibited cutaneous adverse drug reactions associated with oxcarbazepine use between July 2009 and March 2016 at Samsung Medical Center. All of the participants had to discontinue oxcarbazepine despite presenting initially positive responses. Human leukocyte antigen genotyping was performed to detect the genetic predisposition to Stevens-Johnson syndrome. The desensitization to oxcarbazepine was performed with a starting dosage of 0.1 mg/day. Efficacy was evaluated by comparing the frequency of seizures before and at 1 and 3 years after desensitization. Adverse events occurring during desensitization and the retention rate after desensitization were also investigated. Results Nineteen patients (95%) safely completed the desensitization protocol. One withdrew owing to emotional problems that appeared to be associated with oxcarbazepine. The follow-up period was 4.6±1.2 years (mean±SD), and oxcarbazepine was maintained for more than 3 years after desensitization in 15 patients (83.3%). The response rates were 84.2% and 77.8% at 1 and 3 years after desensitization, respectively. Eight patients remained seizure-free for 3 years, and two discontinued all AEDs. Transient adverse reactions such as mild rash and itching were reported by five patients during desensitization. Conclusions This study has demonstrated the long-term efficacy and safety of desensitization to oxcarbazepine in patients exhibiting cutaneous adverse drug reactions. This favorable outcome should encourage the implementation of desensitization in patients presenting with hypersensitivity to oxcarbazepine as an alternative strategy in clinical practice. PMID:27730770

Effect of desensitizing toothpastes on dentin

Directory of Open Access Journals (Sweden)

Shelon Cristina Souza Pinto

2012-10-01

Full Text Available The objective of this study was to analyze the effects of toothbrushing with desensitizing toothpastes on dentin permeability and dentinal tubule occlusion. Fifty rats provided two hundred incisor teeth divided into five groups: DW, brushed with distilled water (control; FT, brushed with fluoride toothpaste; SCT, brushed with strontium chloride toothpaste; PCT, brushed with potassium citrate toothpaste; and PNT, brushed with potassium nitrate toothpaste. Cavities were prepared to expose the dentinal tubules, and the incisor teeth were brushed using the experimental agents. After each treatment, Evans blue dye solution was applied to the teeth. Dentin permeability was analyzed using scanning electron microscopy and energy-dispersive X-rays (EDX. There were significant differences (p < 0.0001, ANOVA among the groups regarding dentin permeability, number of dentinal tubules, diameter of dentinal tubules, and opened tubular area. In the SCT, PCT and PNT groups, opened and partially occluded tubules, deposits, and a few smear layers were observed. In the DW and FT groups, most of the dentinal tubules were open, with no deposits or smear layers on the dentin. EDX revealed peaks of calcium and phosphorus in all of the groups, as well as traces of strontium in the SCT group and of potassium in the PCT and PNT groups. Desensitizing toothpaste decreased dentin permeability, although it produced only partial dentin tubule occlusion.

Desensitization in patients with beta-lactam drug allergy.

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Yusin, J S; Klaustermeyer, W; Simmons, C W; Baum, M

2013-01-01

Patients with a history of beta-lactam antibiotic allergy are often admitted to the hospital with severe or life-threatening infections requiring beta-lactam antibiotics. Strict avoidance of beta lactams to such patients may prevent them from getting adequate coverage and can lead to an increase in the use of alternative antibiotics, which can predispose to antibiotic resistance. Past studies revealed a lower incidence of pen allergy then patients' histories suggest. Fortunately today, there are three options for patients presenting with a history of beta-lactam allergy. Penicillin skin testing, beta-lactam challenge or beta-lactam desensitization. Recently Pre Pen has been FDA re-approved and when combined with Pen G is a valid way to determine if patients are able to tolerate beta-lactam antibiotic. When these agents are not available one must decide about desensitization or challenge. When a patient has a positive penicillin skin test, desensitization or beta-lactam avoidance are the only options. This paper reviews the safety of beta-lactam desensitization. To perform a chart review on patients desensitised with beta lactam to determine if desensitizations can be performed safely without minimal complications. A retrospective chart review was performed on allergy and immunology inpatient consultations for beta-lactam desensitization between September 2003 and August 2006 at the Cedars-Sinai Medical Centre in Los Angeles. Patient data and outcomes of desensitization were analysed. A total of 13 intravenous desensitizations were performed on 12 patients. The patients consisted of eight females and four males with an average age of 65 years. Age range was 36-92 years old. All 13 intravenous desensitizations were completed without complications. No patient required a slower rate of desensitization or discontinuance of the desensitization. Patients were able to tolerate the initial therapeutic dose of their beta-lactam antibiotic and were then able to complete full

Aspirin Desensitization

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... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Aspirin Desensitization Kevin C. Welch, MD Zara Patel, MD Introduction The term "aspirin-sensitive asthma" (also known as "aspirin triad" or " ...

Using humor in systematic desensitization to reduce fear.

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Ventis, W L; Higbee, G; Murdock, S A

2001-04-01

Effectiveness of systematic desensitization for fear reduction, using humorous hierarchy scenes without relaxation, was tested. Participants were 40 students highly fearful of spiders. Using a 24-item behavioral approach test with an American tarantula, participants were matched on fear level and randomly assigned to 1 of 3 treatment groups: (a) systematic desensitization, (b) humor desensitization, and (c) untreated controls. Each participant was seen for 6 sessions, including pretest and posttest. Analyses of covariance of posttest scores revealed that the 2 treatment groups showed greater reduction in fear than the controls on 3 measures but did not differ from each other. Therefore, humor in systematic desensitization reduced fear as effectively as more traditional desensitization. This finding may have therapeutic applications; however, it may also be applicable in advertising to desensitize fear of a dangerous product, such as cigarettes.

Synergistic inhibitory effect of hyperbaric oxygen combined with sorafenib on hepatoma cells.

Directory of Open Access Journals (Sweden)

Hai-Shan Peng

Full Text Available OBJECTIVES: Hypoxia is a common phenomenon in solid tumors, associated with chemotherapy and radiotherapy resistance, recurrence and metastasis. Hyperbaric oxygen (HBO therapy can increase tissue oxygen pressure and content to prevent the resistance, recurrence and metastasis of cancer. Presently, Sorafenib is a first-line drug, targeted for hepatocellular carcinoma (HCC but effective in only a small portion of patients and can induce hypoxia. The purpose of this study is to investigate the effect of HBO in combination with sorafenib on hepatoma cells. METHODS: Hepatoma cell lines (BEL-7402 and SK-Hep1 were treated with HBO at 2 atmosphere absolute pressure for 80 min per day or combined with sorafenib or cisplatin. At different time points, cells were tested for cell growth, colony formation, apoptosis, cell cycle and migration. Finally, miRNA from the hepatoma cells was detected by microRNA array and validated by qRT-PCR. RESULTS: Although HBO, sorafenib or cisplatin alone could inhibit growth of hepatoma cells, HBO combined with sorafenib or cisplatin resulted in much greater synergistic growth inhibition (cell proliferation and colony formation in hepatoma cells. Similarly, the synergistic effect of HBO and sorafenib on induction of apoptosis was also observed in hepatoma cells. HBO induced G1 arrest in SK-Hep1 not in BEL-7402 cells, but enhanced cell cycle arrest induced by sorafenib in BEL-7402 treated cells. However, HBO had no obvious effect on the migration of hepatoma cells, and microRNA array analysis showed that hepatoma cells with HBO treatment had significantly different microRNA expression profiles from those with blank control. CONCLUSIONS: We show for the first time that HBO combined with sorafenib results in synergistic growth inhibition and apoptosis in hepatoma cells, suggesting a potential application of HBO combined with sorafenib in HCC patients. Additionally, we also show that HBO significantly altered microRNA expression

Dioxin-like activity of brominated dioxins as individual compounds or mixtures in in vitro reporter gene assays with rat and mouse hepatoma cell lines.

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Suzuki, G; Nakamura, M; Michinaka, C; Tue, N M; Handa, H; Takigami, H

2017-10-01

In vitro reporter gene assays detecting dioxin-like compounds have been developed and validated since the middle 1990's, and applied to the determination of dioxin-like activities in various samples for their risk management. Data on characterizing the potency of individual brominated dioxins and their activity in mixture with chlorinated dioxins are still limited on the cell-based assay. This study characterized the dioxin-like activities of the 32 brominated dioxins, such as polybrominated dibenzo-p-dioxins, polybrominated dibenzofurans (PBDFs), coplanar polybrominated biphenyls, mixed halogenated dibenzo-p-dioxins and dibenzofurans (PXDFs), as a sole component or in a mixture by DR-CALUX (dioxin-responsive chemically activated luciferase expression) using the rat hepatoma H4IIE cell line and XDS-CALUX (xenobiotic detection systems-chemically activated luciferase expression) assays using the mouse hepatoma H1L6.1 cell line. The 2,3,7,8-TCDD-relative potencies (REPs) of most of the brominated dioxins were within a factor of 10 of the WHO toxicity equivalency factor (WHO-TEF) for the chlorinated analogues. The REPs of a few PXDFs were an order of magnitude higher than the corresponding WHO-TEFs, indicating their toxicological importance. Results with reconstituted mixtures suggest that the activity of brominated and chlorinated dioxins in both CALUX assays was dose-additive. Thus, obtained results indicated the applicability of the CALUX assays as screening tools of brominated dioxins together with their chlorinated analogues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relaxation and Distraction in Experimental Desensitization.

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Weir, R. O.; Marshall, W. L.

1980-01-01

Compared experimental desensitization with a procedure that replaced relaxation with a distraction task and with an approach that combined both relaxation and distraction. Desensitization generally was more effective than the other two procedures. (Author)

Comparative study on lysosomal accumulation of 67Ga and 111In in Morris hepatoma 7316A

International Nuclear Information System (INIS)

Takeda, S.; Uchida, T.; Matsuzawa, T.

1977-01-01

Intracellular localization of 67 Ga and 111 In was investigated in Morris hepatoma 7316A and in normal Buffalo rat liver cells by a cell fractionation method at 48 hr after an intraperitoneal injection of the nuclides. Lysosomal fractions of the tumor and normal liver cells had the highest relative specific radioactivities of the nuclides (p 67 Ga (p 67 Ga seemed to indicate that 67 Ga determines lysosomal functions of tumor cells more precisely than 111 In

Carboplatin hypersensitivity: evaluation and successful desensitization protocol.

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Bruchim, Ilan; Goldberg, Arnon; Fishman, Ami; Confino-Cohen, Ronit

2014-01-01

Carboplatin-induced immediate hypersensitivity reactions are relatively common among patients with gynecological malignancies. Once this occurs, the patient might be at risk for future carboplatin-induced reactions. This study evaluated the efficacy of allergic consultation, carboplatin skin testing and desensitization as a single intervention strategy in this population. Patients with a well-documented immediate reaction to carboplatin were offered allergy consultation, carboplatin skin testing and a desensitization plan in a single visit between scheduled chemotherapy sessions. Fifty-five patients with an immediate reaction were evaluated. After allergist assessment, 44 (89%) of 49 patients skin tested had a positive result. A total of 207 carboplatin desensitization cycles were administered to 49 women. Among them, 10 patients had a mild immediate hypersensitivity reaction during desensitization. Five patients subsequently tolerated carboplatin administered in the prolonged desensitization protocol. In the data presented, we propose a strategy that is both cost effective and very convenient for the patient. The diagnostic procedure, including allergist consultation and skin test, can be completed in less than 2 h. In most cases where carboplatin is indispensable, desensitization can be administered without overnight hospitalization.

Desensitization and recovery of phototropic responsiveness in Arabidopsis thaliana

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Janoudi, A. K.; Poff, K. L.

1993-01-01

Phototropism is induced by blue light, which also induces desensitization, a partial or total loss of phototropic responsiveness. The fluence and fluence-rate dependence of desensitization and recovery from desensitization have been measured for etiolated and red light (669-nm) preirradiated Arabidopsis thaliana seedlings. The extent of desensitization increased as the fluence of the desensitizing 450-nm light was increased from 0.3 to 60 micromoles m-2 s-1. At equal fluences, blue light caused more desensitization when given at a fluence rate of 1.0 micromole m-2 s-1 than at 0.3 micromole m-2 s-1. In addition, seedlings irradiated with blue light at the higher fluence rate required a longer recovery time than seedlings irradiated at the lower fluence rate. A red light preirradiation, probably mediated via phytochrome, decreased the time required for recovery from desensitization. The minimum time for detectable recovery was about 65 s, and the maximum time observed was about 10 min. It is proposed that the descending arm of the fluence-response relationship for first positive phototropism is a consequence of desensitization, and that the time threshold for second positive phototropism establishes a period during which recovery from desensitization occurs.

Endogenous Opiate System and Systematic Desensitization.

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Egan, Kelly J.; And Others

1988-01-01

Administered intravenous infusions to phobic patients prior to systematic desensitization. Saline-infused subjects significantly demonstrated the predicted symptom decrease in response to systematic desensitization, whereas naloxone-infused subjects showed no change. Subject reports and psychophysiological measures of arousal indicated no…

99Tcm pertechnetate uptake by hepatoma cells induced by tissue specific hNIS gene expression

International Nuclear Information System (INIS)

Chen Libo; Luo Quanyong; Yu Yongli; Yuan Zhibin; Lu Hankui; Zhu Ruisen; Guo Lihe

2007-01-01

Objective: Human sodium/iodide symporter (hNIS) gene could be used both as an ideal reporter gene and promising therapeutic gene. Rather than radioiodine, 99 Tc m pertechnetate has been proven to be a better radiopharmaceutical for tracing and imaging purposes. Herein, the authors investigated the feasibility of monitoring hNIS gene expression in hepatoma cells using 99 Tc m pertechnetate as a tracer. Methods: Hepatoma cells MH3924A were stably transfected with recombinant retroviral vector in which hNIS cDNA was driven by murine albumin enhancer/promoter (mAlb) and coupled to hygromycin resistance gene. The uptake and efflux of 99 Tc m pertechnetate by transfected hepatoma cells were tested with 99 Tc m pertechnetate (74 kBq) solution adulterated into the culture media and counted after media suspension discharge at different intervals. In further tests, 50 μmol/L NaClO 4 and 500 μmol/L Ouabain were added into the media for 99 Tc m inhibition tests. For in vive studies, five ACI rats bearing NIS transfected hepatoma xenografts were injected with 99 Tc m pertechnetate (15.8 MBq) and followed by dynamic acquisition (0.57 1, 2 and 4 h) with small gamma camera to semi-quantitatively analyze the radioactivity distribution. Results: In vitro tests, the peak uptake of 99 Tc m pertechnetate by cultured transfected MH3924A cells was up to 254 folds higher than that by the wild type cells. 99 Tc m uptake by transfected cells were significantly inhibited by NaClO 4 down to 2.44% (P 99 Tc m pertechnetate out of cultured transfected cells became rapid immediately after renewal of culture media (half life 99 Tc m accumulations by hNIS transfected tumor xenografts were obvious in early phases of the acquisition with peak uptake at 12 min and gradually declining later on. Conclusions: hNIS transfected hepatoma cells can avidly uptake 99 Tc m pertechnetate both in vitro and in vive. It is feasible to utilize 99 Tc m pertechnetate for monitoring and even quantitatively analyzing

On postirradiation desensitization of the organism to adrenaline

International Nuclear Information System (INIS)

Vasin, M.V.; Petrova, T.V.

1988-01-01

In experiments with albino mongrel rats weighing 220-260 g a study was made of the affect of adrenaline on the cyclic nucleotide content of blood plasma at early times following 60 Co gamma-irradiation (75 Gy). The absence of the organism response to adrenaline is perhaps due to the development of post irradiation desensitization of β-adrenergic system and inability to induce cAMP formation in a cell. The data are submitted confirming the affect of levamisole on the cyclic nucleitide level. The level of cGMP decreased in thymocytes and increased in blood plasma after the administration of the drug to irradiated animals

Aspirin challenge and desensitization: how, when and why.

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Cortellini, Gabriele; Caruso, Cristiano; Romano, Antonino

2017-08-01

To investigate the current approach to aspirin challenge (drug provocation) and/or desensitization in patients with histories of hypersensitivity reactions to it, particularly in those with cardiovascular diseases. The literature indicates that patients with coronary artery disease (CAD), including those with an acute coronary syndrome, may safely undergo low-dose aspirin challenge and/or desensitization. Recently, flowcharts regarding challenge/desensitization procedures with aspirin in patients with CAD and histories of aspirin hypersensitivity reactions have become available. Aspirin desensitization and continuous aspirin therapy constitute an effective option in patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory diseases (NERD) who have suboptimally controlled asthma or rhinosinusitis, or require multiple revision polypectomies. The use of aspirin has proven to reduce morbidity and mortality associated with CAD. There is a general consensus on aspirin's effectiveness in secondary prevention of CAD. Therefore, aspirin desensitization is necessary in patients with CAD and histories of hypersensitivity reactions to it. The effectiveness of aspirin desensitization and continuous therapy in patients with NERD has been shown in numerous studies. However, shared selection criteria of candidates for aspirin challenge/desensitization procedures, and simple and homogeneous protocols are necessary. Moreover, preventive safety measures are still needed in order to reduce the potential risks of these procedures.

Medication Desensitization: Characterization of Outcomes and Risk Factors for Reactions.

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Murray, Taryn S; Rice, Todd W; Wheeler, Arthur P; Phillips, Elizabeth J; Dworski, Ryszard T; Stollings, Joanna L

2016-03-01

Although its mechanisms are poorly understood, desensitization has been used to induce a temporary state of immune unresponsiveness in patients who have IgE-, non-IgE-, or pharmacologically mediated reactions when a drug has no alternatives. The purpose of this study was to characterize the outcomes and identify risk factors for reactions during drug desensitization. A retrospective review of electronic medical records of adult patients undergoing drug desensitization from January 1, 2011, to December 31, 2013, was conducted in 2 intensive care units at a tertiary medical center. We used multivariate analysis to determine if specified risk factors were associated with reacting during the desensitization. Reactions were classified according to the pretest probability prior to desensitization, and then, reactions during desensitization were classified based on the occurrence of cutaneous reactions as follows: successful with no reaction, mild reaction, moderate reaction, or failed. Failure could result from any systemic allergic or cutaneous reaction resulting in procedure termination. The desensitizations were also assessed to determine if the patient required de-escalation secondary to a reaction. A total of 88 desensitizations were performed in 69 patients. Desensitization was completed with no cutaneous reaction in 85% of patients. No baseline characteristic, medication class (P = 0.46), or indication for desensitization (P = 0.59) was associated with having a reaction. Reported histories of urticaria (P desensitization. However, neither history of urticaria nor labored breathing was independently associated with having a reaction in multivariate analysis (OR = 0.979, 95% CI = 0.325-2.952, P = 0.970, and OR = 1.626, 95% CI = 0.536-4.931, P = 0.739, respectively). Drug desensitization is safe for patients who have no alternative for therapy. Reported allergy histories of urticaria and labored breathing are both associated with having a reaction during the

Playing violent video games and desensitization to violence.

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Brockmyer, Jeanne Funk

2015-01-01

This article examines current research linking exposure to violent video games and desensitization to violence. Data from questionnaire, behavioral, and psychophysiologic research are reviewed to determine if exposure to violent video games is a risk factor for desensitization to violence. Real-world implications of desensitization are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Desensitization and recovery of phototropic responsiveness in Arabidopsis thaliana

International Nuclear Information System (INIS)

Janoudi, A.K.; Poff, K.L.

1993-01-01

Phototropism is induced by blue light, which also induces desensitization, a partial or total loss of phototropic responsiveness. The fluence and fluence-rate dependence of densensitization and recovery from desensitization have been measured for etiolated and red light (669-nm) preirradiated Arabidopsis thaliana seedlings. The extent of desensitization increased as the fluence of the desensitizing 450-nm light was increased from 0.3 to 60 μmol m -2 s -1 . At equal fluences, blue light caused more desensitization when given at a fluence rate of 1.0 μmol m -2 s -1 than at 0.3 μmol m -2 s -1 . In addition, seedlings irradiated with blue light at the higher fluence rate required a longer recovery time than seedlings irradiated at the lower fluence rate. A red light preirradiation, probably mediated via phytochrome, decreased the time required for recovery from desensitization. The minimum time for detectable recovery was about 65 s, and the maximum time observed was about 10 min. It is proposed that the descending arm of the fluence-response relationship for first positive phototropism is a consequence of desensitization, and that the time threshold for second positive phototropism establishes a period during which recovery from desensitization occurs. 11 refs., 6 figs

Guided Mastery and Performance Desensitization Treatments.

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Williams, S. Lloyd; And Others

1985-01-01

Compared desensitization and self-efficacy models of phobia treatment in height phobics. Self-efficacy treatment proved to be significantly more effective than desensitization treatment in restoring subjects' behavioral functioning, in raising their perceptions of self-efficacy, and in reducing their anticipated anxiety and thoughts of danger.…

Skeletal metastases from hepatoma: frequency, distribution, and radiographic features

International Nuclear Information System (INIS)

Kuhlman, J.E.; Fishman, E.K.; Leichner, P.K.; Magid, D.; Order, S.E.; Siegelman, S.S.

1986-01-01

Over the past 6 years, the authors evaluated 300 patients with hepatoma as part of phase 1 and 2 treatment protocol trials. Analysis of the available clinical data and radiographic studies revealed 22 patients (7.3%) with skeletal metastases demonstrated by radiography, computed tomography (CT), and/or nuclear scintigraphy. The plain film appearance of skeletal metastases from hepatoma was osteolytic in all cases. CT scanning best demonstrated the expansile, destructive nature of these metastases, which were often associated with large, bulky soft-tissue masses. Skeletal metastases from hepatomas demonstrated increased radiotracer uptake on standard bone scans and were gallium avid, similar to the hepatoma itself. In addition, they could be targeted therapeutically with I-131 antiferritin immunoglobulin. The most frequent sites of skeletal metastases were the ribs, spine, femur, pelvis, and humerus. An initial symptom in ten patients was skeletal pain corresponding to the osseous metastases. In five patients, pathologic fractures of the proximal femur or humerus developed and required total hip replacement or open-reduction internal fixation. Patients with long-standing cirrhosis or known hepatocellular carcinoma who also have skeletal symptoms should be evaluated for possible osseous metastases

Group Vicarious Desensitization of Test Anxiety.

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Altmaier, Elizabeth Mitchell; Woodward, Margaret

1981-01-01

Studied test-anxious college students (N=43) who received either vicarious desensitization, study skills training, or both treatments; there was also a no-treatment control condition. Self-report measures indicated that vicarious desensitization resulted in lower test and trait anxiety than study skills training alone or no treatment. (Author)

Relaxation as a Factor in Semantic Desensitization

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Bechtel, James E.; McNamara, J. Regis

1975-01-01

Relaxation and semantic desensitization were used to alleviate the fear of phobic females. Results showed that semantic desensitization, alone or in combination with relaxation, failed to modify the evaluative meanings evoked by the feared object. (SE)

Desensitization protocols and their outcome.

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Marfo, Kwaku; Lu, Amy; Ling, Min; Akalin, Enver

2011-04-01

In the last decade, transplantation across previously incompatible barriers has increasingly become popular because of organ donor shortage, availability of better methods of detecting and characterizing anti-HLA antibodies, ease of diagnosis, better understanding of antibody-mediated rejection, and the availability of effective regimens. This review summarizes all manuscripts published since the first publication in 2000 on desensitized patients and discusses clinical outcomes including acute and chronic antibody-mediated rejection rate, the new agents available, kidney paired exchange programs, and the future directions in sensitized patients. There were 21 studies published between 2000 and 2010, involving 725 patients with donor-specific anti-HLA antibodies (DSAs) who underwent kidney transplantation with different desensitization protocols. All studies were single center and retrospective. The patient and graft survival were 95% and 86%, respectively, at a 2-year median follow-up. Despite acceptable short-term patient and graft survivals, acute rejection rate was 36% and acute antibody-mediated rejection rate was 28%, which is significantly higher than in nonsensitized patients. Recent studies with longer follow-up of those patients raised concerns about long-term success of desensitization protocols. The studies utilizing protocol biopsies in desensitized patients also reported higher subclinical and chronic antibody-mediated rejection. An association between the strength of DSAs determined by median fluorescence intensity values of Luminex single-antigen beads and risk of rejection was observed. Two new agents, bortezomib, a proteasome inhibitor, and eculizumab, an anti-complement C5 antibody, were recently introduced to desensitization protocols. An alternative intervention is kidney paired exchange, which should be considered first for sensitized patients. © 2011 by the American Society of Nephrology

Adenosine receptor desensitization and trafficking.

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Mundell, Stuart; Kelly, Eamonn

2011-05-01

As with the majority of G-protein-coupled receptors, all four of the adenosine receptor subtypes are known to undergo agonist-induced regulation in the form of desensitization and trafficking. These processes can limit the ability of adenosine receptors to couple to intracellular signalling pathways and thus reduce the ability of adenosine receptor agonists as well as endogenous adenosine to produce cellular responses. In addition, since adenosine receptors couple to multiple signalling pathways, these pathways may desensitize differentially, while the desensitization of one pathway could even trigger signalling via another. Thus, the overall picture of adenosine receptor regulation can be complex. For all adenosine receptor subtypes, there is evidence to implicate arrestins in agonist-induced desensitization and trafficking, but there is also evidence for other possible forms of regulation, including second messenger-dependent kinase regulation, heterologous effects involving G proteins, and the involvement of non-clathrin trafficking pathways such as caveolae. In this review, the evidence implicating these mechanisms is summarized for each adenosine receptor subtype, and we also discuss those issues of adenosine receptor regulation that remain to be resolved as well as likely directions for future research in this field. Copyright © 2010 Elsevier B.V. All rights reserved.

Systematic Desensitization as Training in Self-Control

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Goldfried, Marvin R.

1971-01-01

A description of a mediational model to explain the effectiveness of desensitization and a discussion of the available corroborative research findings for this alternative explanation are given. Also, specific procedural modifications for systematic desensitization are suggested. (Author)

Neonatal Desensitization Supports Long-Term Survival and Functional Integration of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Rat Joint Cartilage Without Immunosuppression

Science.gov (United States)

Zhang, Shufang; Jiang, Yang Zi; Zhang, Wei; Chen, Longkun; Tong, Tong; Liu, Wanlu; Mu, Qin; Liu, Hua; Ji, Junfeng; Ouyang, Hong Wei

2013-01-01

Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d+s+c) or a collagen bilayer scaffold (group d+s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s+c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d+s+c exhibited greater International Cartilage Repair Society (ICRS) scores than group d+s or group s+c. Abundant collagen type II and improved mechanical properties were detected in group d+s+c. There were less CD4+ inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d+s+c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models. PMID:22788986

Desensitization to clopidogrel: a tailor-made protocol.

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Barreira, P; Cadinha, S; Malheiro, D; Moreira da Silva, J P

2014-01-01

Clopidogrel is an antiplatelet drug widely used for treatment and prevention of a variety of cardiovascular diseases. We report a successful desensitization to clopidogrel in a 70-year-old Caucasian man with delayed hypersensitivity (HS) reaction. He developed lip, hand and foot swelling, erythematous papular non-pruritic lesions and arthralgias 2 weeks after starting treatment with clopidogrel 75 mg/d. A 3-hour desensitization protocol was started, achieving a cumulative dose of 154 mg without any reaction, and a daily dose of 75 mg was recommended. On the 4th day, the patient developed skin lesions similar to the previously described. He was treated with topical steroids and oral antihistamines, and the daily dose of clopidogrel was reduced to 20 mg. A new desensitization protocol was established, with a slow dose increment, according to the patient's response. It was only possible to achieve the dose of 75 mg/d after 2 months. Although well tolerated by most patients, HS reactions with clopidogrel may occur and desensitization is rising as a safe alternative in those patients. In delayed reactions with cutaneous lesions, a slower desensitization protocol may be necessary, as in this case.

Rituximab desensitization in three patients with severe rituximab allergy.

Science.gov (United States)

Öztürk, Erman; Özyiğit, Leyla Pur; Öztürk, Ayşe Bilge; Akay, Meltem Olga; Çetiner, Mustafa; Ferhanoğlu, Burhan

Rituximab is a chimeric monoclonal antibody that targets CD20 positive B cells and has a positive effect on both overall and progression-free survival in B-cell lymphoid malignancies. Combination rituximab with chemotherapy treatment provide survival improvement. Although rituximab is an important treatment option in hematological malignancies, the risk of allergic reactions is high. These reactions are usually IgE-mediated and can be varied in regard of severity from urticaria to anaphylaxis. It is an option to interrupt the treatment and ommit rituximab therapy who had allergic reactions. Drug desensitization is another option and successful results have been reported by applying desensitization to such reactions. Drug desensitization alters the immune response to induce a state of temporary clinical tolerance to the allergic drug by giving gradual increasing of doses of drug at fixed time intervals. Herein, we present 3 cases successfully treated with rituximab desensitization. The cases were using rituximab with the diagnosis of Burkitt lymphoma, follicular lymphoma, and marginal zone lymphoma, respectively. Two cases had grade 2 and 1 case had grade 3 systemic allergic reaction with rituximab. There was no known allergy history in all 3 cases. All patients tolerated the desensitization protocol. The subsequent treatments of the patients were also given by desensitization protocol. A total of 12 desensitizations were administered to 3 cases. No severe or life-threating reactions were observed in subsequent applications. To date applying desensitization protocols ensure rituximab treatment safely. Rituximab desensitization can be performed at trained allergy centers, and it may be an appropriate option for rituximab allergic patients. Copyright © 2017 Elsevier Inc. All rights reserved.

GABAB receptor phosphorylation regulates KCTD12-induced K+ current desensitization

DEFF Research Database (Denmark)

Adelfinger, L; Turecek, R; Ivankova, K

2014-01-01

released from the G-protein. Receptor-activated K+ currents desensitize in the sustained presence of agonist to avoid excessive effects on neuronal activity. Desensitization of K+ currents integrates distinct mechanistic underpinnings. GABAB receptor activity reduces protein kinase-A activity, which...... reduces phosphorylation of serine-892 in GABAB2 and promotes receptor degradation. This form of desensitization operates on the time scale of several minutes to hours. A faster form of desensitization is induced by the auxiliary subunit KCTD12, which interferes with channel activation by binding to the G......-protein βγ subunits. Here we show that the two mechanisms of desensitization influence each other. Serine-892 phosphorylation in heterologous cells rearranges KCTD12 at the receptor and slows KCTD12-induced desensitization. Likewise, protein kinase-A activation in hippocampal neurons slows fast...

Synthesis of PBAD-lipiodol nanoparticles for combination treatment with boric acid in boron neutron capture therapy for hepatoma in-vitro

International Nuclear Information System (INIS)

Chou, F.I.; Chung, H.P.; Liu, H.M.; Wen, H.W.; Chi, C.W.; Lin, Shanyang; Lui, W.Y.; Kai, J.J.

2006-01-01

This study attempted to increase BNCT efficiency for hepatoma by a combined treatment of phenylboric acid derivative entrapped lipiodol nanoparticles (PBAD-L nanoparticles) with boric acid. The size of PBAD-L nanoparticles were 400-750 nm at the boron concentrations of 0.3-2.7 mg/ml. After 24 hours the boron concentration in PBAD-L nanoparticles treated human hepatoma HepG2 cells was 112 ppm, while that in rat liver Clone 9 cells was 52 ppm. With the use of 25 μg B/ml boric acid, after 6 hours the boron concentration in HepG2 and Clone 9 cells were 75 ppm and 40 ppm, respectively. In a combined treatment, boron concentration in HepG2 cells which were treated with PBAD-L nanoparticles for 18 hours and then combined with boric acid for 6 hours was 158 ppm. After neutron irradiation, the surviving fraction of HepG2 cells treated with PBAD-L nanoparticles was 12.6%, while that in the ones with a combined treatment was 1.3%. In conclusion, the combined treatment provided a higher boron concentration in HepG2 cells than treatments with either PBAD-L nanoparticles or boric acid, resulting in a higher therapeutic efficacy of BNCT in hepatoma cells. (author)

Relationship Factors in Desensitization: A Persistent Trend

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Nawas, M. Mike; Pucel, John C.

1971-01-01

The aim of the study was to explore the relevance to the outcome of desensitization of same-sex and opposite-sex pairings of subjects and experimenters. It was concluded that desensitization is independent of the sex pairing of subject and experimenter. (Author)

Characterization of phosphorylated beta-adrenergic receptors from desensitized turkey erythrocytes

International Nuclear Information System (INIS)

Rebar, R.; Crooke, S.T.; Stadel, J.M.

1986-01-01

Catecholamine-induced desensitization of turkey erythrocyte (TE) adenylate cyclase results in a 40-50 percent decrease in agonist stimulated cyclase activity. Desensitization is accompanied by decreased mobility on SDS-PAGE of beta-adrenergic receptor (BAR) proteins photoaffinity labeled with [ 125 I]-p-azidobenzylcarazolol compared to control. Using a low crosslinked gel, the M/sub r/ = 42,000 band of BAR from desensitized TE was further resolved into a doublet compared to a single M/sub r/ = 38,000 band for control. The formation of the doublet appears to correlate with the amount of adenylate cyclase desensitization. Preincubating TE for 20 hr at 37 0 C with 32 P-/sub i/ labels BAR. 32 P-BAR was partially purified by affinity chromatography over alprenolol-Sepharose. Limited digest peptide maps of 32 P-BAR using papain identified a unique peptide (M/sub r/ = 2800) from BAR of desensitized TE which was absent in control. This unique 32 P-peptide was found only in the upper band of the doublet of BAR from desensitized TE. These data indicate that BAR is not uniformly phosphorylated following agonist-induced desensitization of TE and identify a peptide of BAR which is a site of phosphorylation correlating with desensitization of TE adenylate cyclase

Aspirin Desensitization in Patients With Coronary Artery Disease: Results of the Multicenter ADAPTED Registry (Aspirin Desensitization in Patients With Coronary Artery Disease).

Science.gov (United States)

Rossini, Roberta; Iorio, Annamaria; Pozzi, Roberto; Bianco, Matteo; Musumeci, Giuseppe; Leonardi, Sergio; Lettieri, Corrado; Bossi, Irene; Colombo, Paola; Rigattieri, Stefano; Dossena, Cinzia; Anzuini, Angelo; Capodanno, Davide; Senni, Michele; Angiolillo, Dominick J

2017-02-01

There are limited data on aspirin (ASA) desensitization for patients with coronary artery disease. The aim of the present study was to assess the safety and efficacy of a standard rapid desensitization protocol in patients with ASA sensitivity undergoing coronary angiography. This is a prospective, multicenter, observational study including 7 Italian centers including patients with a history of ASA sensitivity undergoing coronary angiography with intent to undergo percutaneous coronary intervention. A total of 330 patients with history of ASA sensitivity with known/suspected stable coronary artery disease or presenting with an acute coronary syndrome, including ST-segment-elevation myocardial infarction were enrolled. Adverse effects to aspirin included urticaria (n=177, 53.6%), angioedema (n=69, 20.9%), asthma (n=65, 19.7%), and anaphylactic reaction (n=19, 5.8%). Among patients with urticaria/angioedema, 13 patients (3.9%) had a history of idiopathic chronic urticaria. All patients underwent a rapid ASA (5.5 hours) desensitization procedure. The desensitization procedure was performed before cardiac catheterization in all patients, except for those (n=78, 23.6%) presenting with ST-segment-elevation myocardial infarction who underwent the desensitization after primary percutaneous coronary intervention. Percutaneous coronary intervention was performed in 235 patients (71%) of the overall study population. The desensitization procedure was successful in 315 patients (95.4%) and in all patients with a history of anaphylactic reaction. Among the 15 patients (4.6%) who did not successfully respond to the desensitization protocol, adverse reactions were minor and responded to treatment with corticosteroids and antihistamines. Among patients with successful in-hospital ASA desensitization, 253 patients (80.3%) continued ASA for at least 12 months. Discontinuation of ASA in the 62 patients (19.7%) who had responded to the desensitization protocol was because of medical

Preparation of [[sup 131]I]lipiodol as a hepatoma therapeutic agent

Energy Technology Data Exchange (ETDEWEB)

Jiunnguang Lo; Aiyih Wang; Yuanyaw Wei (National Tsinghua Univ., Hsinchu (Taiwan). Inst. of Nuclear Science); Wingyiu Lui; Chinwen Chi (Taipei Veterans General Hospital, Taipei (Taiwan)); Wingkai Chan (Academia Sinica, Taipei (Taiwan). Inst. of Biomedical Sciences)

1992-12-01

An isotopic exchange method was used to label lipiodol with [sup 131]I. The labelling efficiency was > 92.5%, and the radiochemical purity of [[sup 131]I]lipiodol was above 98% as determined by ITLC. The influencing factors e.g. the heating temperature, reaction, pH and storage conditions were studied and the optimum conditions were determined. In a pilot study injecting [[sup 131]I]lipiodol for the treatment of hepatoma, about 70% of hepatoma patients had a response to the treatment with a reduction of [alpha]-fetoprotein and decrease of hepatoma sizes. The overall median survival was 9 months (range 2-17 months). (author).

Systematic Desensitization Of Test Anxiety: A Comparison Of Group And Individual Treatment

Science.gov (United States)

Scissons, Edward H.; Njaa, Lloyd J.

1973-01-01

The results indicate the effectiveness of both individual desensitization and group desensitization in the treatment of high test anxiety. More research is needed in comparing the effectiveness of group desensitization and individual desensitization with intratreatment variables. (Author)

Recovery from desensitization of IgE-dependent responses in human lung mast cells.

Science.gov (United States)

Lewis, A; MacGlashan, D W; Suvarna, S K; Peachell, P T

2017-08-01

Clinical desensitization and oral food immunotherapy are therapeutic interventions that allow individuals who react adversely to an allergen (drug or food) to be made tolerant to the allergen. However, tolerance is brief, and allergen hypersensitivity can recur within days following allergen withdrawal. We hypothesize that the reason these treatments are temporary reflects rapid recovery of mast cells from a desensitized state. We sought to test this. Desensitization of IgE-mediated histamine release from human lung mast cells was explored by methods that partially replicate the pattern of treatment during clinical desensitization. Specific and non-specific desensitization and changes in surface IgE were examined following desensitization. Recovery from desensitization was also studied. Desensitization of mast cell responses was readily induced with concentrations of antigen or anti-IgE that were suboptimal for secretion. There was little or no non-specific desensitization when lung mast cells were exposed to antigens. There was no loss of cell surface IgE following desensitization. Removing the desensitizing stimulus from the media following desensitization allowed the cells to recover with half-point of recovery of ~1.5 days and complete recovery after 5 days. Both the functional response and histamine content recovered within this time frame. The recovery appeared possible because both antigens and anti-IgE dissociated rapidly from cells after washing to remove excess stimulus. Human lung mast cells readily recover from a desensitized state following removal of desensitizing antigen. This finding provides a potential explanation for the ephemeral nature of clinical desensitization. © 2017 John Wiley & Sons Ltd.

Incidence and significance of pleural effusion after hepatoma surgery

International Nuclear Information System (INIS)

Song, Jae Uoo; Im, Jung Gi; Ahn, Joong Mo; Kim, Seung Cheol; Kim, Sam Soo; Kim, Seung Hoon; Yeon, Kyung Mo

1994-01-01

We performed this study to evaluate the clinical significance and temporal changes of pleural effusion developed after the resection of hepatoma. We reviewed retrospectively follow-up chest radiographs of 97 patients who had undergone operation for hepatoma and had no radiologically demonstrable postoperative complications. The duration of pleural effusion was classified into five groups and the amount of pleural effusion at one week after operation was graded into four groups. Statistical significance of the relationship between the duration, amount of pleural effusion and five factors, which are location and size of tumor, age of the patients, methods of operation, and preoperative liver function, was studied respectively. Pleural effusion was developed in 63.9% (62/97) and the mean duration was 2.5 weeks. In 92% (52/56), pleural effusion disappeared spontaneously within four weeks. Patients who had hepatoma in upper portion of the right lobe developed more frequent pleural effusion which persisted longer, and was larger in amount at one week after operation(p<0.05). There were no statistically significant differences between pleural effusion and the other four factors. Pleural effusion following hepatoma surgery should not be regarded as a sign of post-operative complication, as it invariably disappears spontaneously within four weeks. Development of pleural effusion is considered to be caused by local irritation and disturbance of lymphatic flow at the diaphragm

Liver regeneration in mice bearing a transplanted hepatoma.

Science.gov (United States)

Badran, A F; Moreno, F R; Echave Llanos, J M

1984-01-01

The hepatocyte mitotic index curve in hepatectomized hepatoma-bearing mice, rises earlier, has a greater amplitude and is less synchronized than that of normal hepatectomized mice. This indicates a stimulation (more mitosis in a shorter time period) produced by the presence of the tumors. The sinusoid litoral cells mitotic index curve in hepatectomized hepatoma-bearing mice appears earlier and is much less synchronized than that of normal hepatectomized mice. Nevertheless both curves have the same amplitude for the whole sampling period and the early stimulation is quickly compensated by lower values (apparent inhibition) appearing in the resting (light) period.

Comment on the Status of Systematic Desensitization

Science.gov (United States)

McGlynn, F. Dudley; Smitherman, Todd A.; Gothard, Kelly D.

2004-01-01

Articles about systematic desensitization that appeared in mainstream behavior therapy journals between the years 1970 and 2002 were counted. Graphic displays of the data point to a sudden and lasting decline of interest in systematic desensitization among academics and researchers. A questionnaire concerning clinical use of orthodox systematic…

The clinical dilemma of "silent desensitization" in aspirin-exacerbated respiratory disease.

Science.gov (United States)

White, Andrew A; Bosso, John V; Stevenson, Donald D

2013-01-01

Aspirin desensitization is a treatment option for patients with aspirin-exacerbated respiratory disease (AERD). Some patients with an excellent history of aspirin or nonsteroidal anti-inflammatory drug (NSAID) reactions have negative aspirin challenges/desensitization. This study discusses the clinical entity of silent desensitization in AERD and the dilemma that this presents to the practicing allergist/immunologist. We discuss a series of patients with a strong history of NSAID reactions who initially underwent a negative challenge/silent desensitization. These patients were subsequently proven to have AERD after a second positive aspirin challenge. Silent desensitization is an uncommon but important outcome to recognize in AERD. Clinicians performing aspirin desensitization should understand that this can occur and consider a second confirmatory aspirin challenge in some patients.

Rapid desensitization of mice with anti-FcγRIIb/FcγRIII mAb safely prevents IgG-mediated anaphylaxis.

Science.gov (United States)

Khodoun, Marat V; Kucuk, Zeynep Yesim; Strait, Richard T; Krishnamurthy, Durga; Janek, Kevin; Clay, Corey D; Morris, Suzanne C; Finkelman, Fred D

2013-12-01

Stimulatory IgG receptors (FcγRs) on bone marrow-derived cells contribute to the pathogenesis of several autoimmune and inflammatory disorders. Monoclonal antibodies that block FcγRs might suppress these diseases, but they can induce anaphylaxis. We wanted to determine whether a rapid desensitization approach can safely suppress IgG/FcγR-mediated anaphylaxis. Mice were injected with serially increasing doses of 2.4G2, a rat mAb that blocks the inhibitory FcγR, FcγRIIb, and the stimulatory receptor, FcγRIII. Rectal temperature was used to detect the development of anaphylaxis. Passive and active IgG-mediated anaphylaxis were evaluated in mice that had been rapidly desensitized with 2.4G2 or mock-desensitized in mice in which monocyte/macrophages, basophils, or neutrophils had been depleted or desensitized and in mice in which FcγRI, FcγRIII, and/or FcγRIV had been deleted or blocked. Rapid desensitization with 2.4G2 prevented 2.4G2-induced shock and completely suppressed IgG-mediated anaphylaxis. Rapid desensitization of ovalbumin-sensitized mice with 2.4G2 was safer and more effective than rapid desensitization with ovalbumin. 2.4G2 treatment completely blocked FcγRIII and removed most FcγRI and FcγRIV from nucleated peripheral blood cells. Because IgG(2a)-mediated anaphylaxis was partially FcγRI and FcγRIV dependent, the effects of 2.4G2 on FcγRI and FcγRIV were probably crucial for its complete inhibition of IgG(2a)-mediated anaphylaxis. IgG(2a)-mediated anaphylaxis was partially inhibited by depletion or desensitization of monocyte/macrophages, basophils, or neutrophils. IgG-mediated anaphylaxis can be induced by ligation of FcγRI, FcγRIII, or FcγRIV on monocycte/macrophages, basophils, or neutrophils and can be safely suppressed by rapid desensitization with anti-FcγRII/RIII mAb. A similar approach may safely suppress other FcγR-dependent immunopathology. Published by Mosby, Inc.

Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and {beta}-adrenergic desensitization in heart failure after myocardial infarction in rats

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Igawa, Akihiko; Nozawa, Takashi; Yoshida, Naohiro [Toyama Medical and Pharmaceutical Univ. (Japan)] [and others

2002-11-01

One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of {beta}-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by {sup 131}I-metaiodobenzylguanidine (MIBG), {beta}-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to {beta}-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of {beta}-adrenergic pathway in this model of heart failure. (author)

Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and β-adrenergic desensitization in heart failure after myocardial infarction in rats

International Nuclear Information System (INIS)

Igawa, Akihiko; Nozawa, Takashi; Yoshida, Naohiro

2002-01-01

One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of β-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by 131 I-metaiodobenzylguanidine (MIBG), β-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to β-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of β-adrenergic pathway in this model of heart failure. (author)

Various imaging methods in the detection of small hepatomas

International Nuclear Information System (INIS)

Nakatsuka, Haruki; Kaminou, Toshio; Takemoto, Kazumasa; Takashima, Sumio; Kobayashi, Nobuyuki; Nakamura, Kenji; Onoyama, Yasuto; Kurioka, Naruto

1985-01-01

Fifty-one patients with small hepatomas under 5 cm in diameter were studied to compare the detectability of various imaging methods. Positive finding was obtained in 50 % of the patients by scintigraphy, in 74 % by ultrasonography and in 79 % by CT during screening tests. Rate of detection in retrospective analysis, after the site of the tumor had been known, were 73 %, 93 % and 87 % respectively. Rate of detection was 92 % by celiac arteriography and 98 % by selective hepatic arteriography. In 21 patients, who had the tumor under 3 cm, the rate was 32 % for scintigraphy, 74 % for ultrasonography and 65 % for CT during screening, whereas it was 58 %, 84 % and 75 % retrospectively. By celiac arteriography, it was 85 %, and by hepatic arteriography, 95 %. Rate of detection of small hepatomas in screening tests differed remarkably from that in retrospective analysis. No single method of imaging can disclose reliably the presense of small hepatoma, therefore more than one method should be used in screening. (author)

Efficacy, outcomes, and cost-effectiveness of desensitization using IVIG and rituximab.

Science.gov (United States)

Vo, Ashley A; Petrozzino, Jeffrey; Yeung, Kai; Sinha, Aditi; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Mackowiak, John; Jordan, Stanley C

2013-03-27

Transplantation rates are very low for the broadly sensitized patient (panel reactive antibody [PRA]>80%; HS). Here, we examine the efficacy, outcomes, and cost-effectiveness of desensitization using high-dose intravenous immunoglobulin (IVIG) and rituximab to improve transplantation rates in HS patients. From July 2006 to December 2011, 207 HS (56 living donors/151 deceased donors) patients (donor-specific antibody positive, PRA>80%) were desensitized using IVIG and rituximab. After desensitization, responsive patients proceeded to transplantation with an acceptable crossmatch. Cost and outcomes of desensitization were compared with dialysis. Of the 207 treated patients, 146 (71%) were transplanted. At 48 months, patient and graft survival by Kaplan-Meier were 95% and 87.5%, respectively. The total 3-year cost for patients treated in the desensitization arm was $219,914 per patient compared with $238,667 per patient treated in the dialysis arm. Thus, each patient treated with desensitization is estimated to save the U.S. healthcare system $18,753 in 2011 USD. Overall, estimated patient survival at the end of 3 years was 96.6% for patients in the desensitization arm of the model (based on Cedars-Sinai survival rate) compared with 79.0% for an age, end-stage renal disease etiology, and PRA matched group of patients remaining on dialysis during the study period. We conclude that desensitization with IVIG+rituximab is clinically and cost-effective, with both financial savings and an estimated 17.6% greater probability of 3-year survival associated with desensitization versus dialysis alone. However, the benefits of desensitization and transplantation are limited by organ availability and allocation policies.

Serum concentration of alpha-1-fetoprotein suggestive of, or pathognomonic for hepatoma

International Nuclear Information System (INIS)

Polterauer, P.; Horak, W.; Legenstein, E.; Mueller, M.

1979-01-01

A short review of alpha-1-fetoprotein (AFP), is followed by a presentation of the serum AFP concentrations obtained in healthy subjects and in patients with hepatoma, cirrhosis of the liver or metastatic liver cancer, measured by radioimmunoassay (RIA). A calculation is made from these results of the upper limit of normal (9 ng/ml), a limit which is suggestive of hepatome (215 ng/ml) and a limit which is pathognomonic for hepatoma (7500 ng/ml). It is concluded that the quantitative determination of AFP by RIA represents a sensitive method which provides valuable clinical information for the early diagnosis of hepatoma. (author)

Aspirin desensitization in aspirin-sensitive asthma: failure to maintain a desensitized state during prolonged therapy.

Science.gov (United States)

Dankner, R E; Wedner, H J

1983-11-01

A patient with a history of asthma induced by acetylsalicylic acid (ASA) was found to be ASA sensitive when orally challenged with ASA. She was successfully desensitized using incremental doses of ASA given orally and maintained on ASA or other nonsteroidal antiinflammatory (NSAI) agents for the treatment of arthritis. After 6 months of uninterrupted therapy the patient developed asthmatic symptoms that were related to ASA and NSAI drug therapy. Although desensitization may be achieved in patients with ASA-sensitive asthma, sensitivity may recur despite continuous therapy.

Nursing Care of Patients Undergoing Chemotherapy Desensitization: Part II.

Science.gov (United States)

Jakel, Patricia; Carsten, Cynthia; Carino, Arvie; Braskett, Melinda

2016-04-01

Chemotherapy desensitization protocols are safe, but labor-intensive, processes that allow patients with cancer to receive medications even if they initially experienced severe hypersensitivity reactions. Part I of this column discussed the pathophysiology of hypersensitivity reactions and described the development of desensitization protocols in oncology settings. Part II incorporates the experiences of an academic medical center and provides a practical guide for the nursing care of patients undergoing chemotherapy desensitization.
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HYPOLIPIDEMIC EFFECT OF ARGLABIN IN HEPATOMA TISSUE CULTURE

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A. V. Ratkin

2015-01-01

Full Text Available Objective. Investigation of hypolipidemic effect of sesquiterpene γ-lactone Arglabin in hepatoma tissue culture (HTC.Materials and methods. In this study we’ve evaluated the effect of sesquiterpene γ-lactone Arglabin and gemfibrozil (reference drug on the lipid content in the hepatoma tissue culture (HTC which were incubated with a fat emulsion “Lipofundin” by fluorescent method with vital dye Nile Red. The cell viability was investigated using the MTT-test and staining by Trypan blue.Results. Cultivation of cell cultures of rat’s hepatoma cell line HTC with Arglabin and gemfibrozil in concentrations from 10 to 50 μmol and from 0.25 to 0.5 mmol, respectively, had no cytotoxic effect. HTC cell viability did not change compared with the corresponding rate in the control culture. Experimental hyperlipidemia in hepatoma culture was induced by the addition in the incubation medium of fat emulsion “Lipofundin” in a final concentration of 0.05 %. The fluorescence intensity of Nile Red in the cells was increased 4-fold (p < 0.05, which indicates a significant accumulation of lipids in the cytosol of cells. In these steady-state Arglabin and gemfibrozil at concentrations 75–100 μM and 0.25–1.0 mM, respectively, reduced the content of lipid in cells. Conclusion. In the model of hyperlipidemia induced by lipofundin, sesquiterpene γ-lactone Arglabin prevents the accumulation of lipids in the HTC cell line, as evidenced by a decrease in Nile Red fluorescence. However hypolipidemic effect of Arglabin is associated with cytotoxic effects, which is typical for anticancer drugs.

Nursing Care of Patients Undergoing Chemotherapy Desensitization: Part I.

Science.gov (United States)

Jakel, Patricia; Carsten, Cynthia; Braskett, Melinda; Carino, Arvie

2016-02-01

Hypersensitivity reactions to chemotherapeutic agents can cause the discontinuation of first-line therapies. Chemotherapy desensitization is a safe, but labor-intensive, process to administer these important medications. A desensitization protocol can enable a patient to receive the entire target dose of a medication, even if the patient has a history of severe infusion reactions. In this article, the authors explain the pathophysiology of hypersensitivity reactions and describe the recent development of desensitization protocols in oncology. In part II of this article, which will appear in the April 2016 issue of the Clinical Journal of Oncology Nursing, the authors will give a detailed account of how a desensitization protocol is performed at an academic medical center.
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Desensitization for solid organ and hematopoietic stem cell transplantation.

Science.gov (United States)

Zachary, Andrea A; Leffell, Mary S

2014-03-01

Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft. © 2014 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

Substance P receptor desensitization requires receptor activation but not phospholipase C

International Nuclear Information System (INIS)

Sugiya, Hiroshi; Putney, J.W. Jr.

1988-01-01

Previous studies have shown that exposure of parotid acinar cells to substance P at 37 degree C results in activation of phospholipase C, formation of [ 3 H]inositol 1,4,5-trisphosphate (IP 3 ), and persistent desensitization of the substance P response. In cells treated with antimycin in medium containing glucose, ATP was decreased to ∼20% of control values, IP 3 formation was completely inhibited, but desensitization was unaffected. When cells were treated with antimycin in the absence of glucose, cellular ATP was decreased to ∼5% of control values, and both IP 3 formation and desensitization were blocked. A series of substance P-related peptides increased the formation of [ 3 H]IP 3 and induced desensitization of the substance P response with a similar rank order of potencies. The substance P antagonist, [D-Pro 2 , D-Try 7,9 ]-substance P, inhibited substance P-induced IP 3 formation and desensitization but did not induce desensitization. These results suggest that the desensitization of substance P-induced IP 3 formation requires agonist activation of a P-type substance P receptor, and that one or more cellular ATP-dependent processes are required for this reaction. However, activation of phospholipase C and the generation of inositol phosphates does not seem to be a prerequisite for desensitization

Computed tomographic evaluation of the portal vein in the hepatomas

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Lee, Kee Hyung; Lee, Seung Chul; Bae, Man Gil; Seo, Heung Suk; Kim, Soon Yong; Lee, Min Ho; Kee, Choon Suhk; Park, Kyung Nam [Hanyang University College of Medicine, Seoul (Korea, Republic of)

1986-10-15

Computed tomography and pornographic findings of 63 patients with hepatoma, undergone hepatic angiography and superior mesenteric pornography for evaluation of tumor and thrombosis of portal vein and determination of indication of transcatheter arterial embolization for palliative treatment of hepatoma from April, 85 to June, 86 in Hanyang university hospital, were reviewed. The results were as follows: 1. In 36 cases, portal vein thrombosis was detected during photography. Nineteen of 37 cases which revealed localized hepatoma in the right lobe of the liver showed portal vein thrombosis; 9 of 11 cases of the left lobe; 8 of 14 cases which were involved in entire liver revealed thrombosis. One case localized in the caudate lobe showed no evidence of invasion to portal vein. 2. Twenty-four of 34 cases with diffuse infiltrative hepatoma revealed portal vein thrombosis and the incidence of portal vein thrombosis in this type were higher than in the cases of the nodular type. 3. The portal vein thrombosis appeared as filling defects of low density in the lumen of the portal veins in CT and they did not reveal contrast enhancement. 4. CT revealed well the evidence of obstructions in the cases of portal vein thrombosis and the findings were well-corresponded to the findings of the superior mesenteric photography. 5. Five of the cases of the portal vein thrombosis were missed in the CT and the causes were considered as due to partial volume effect of enhanced portal vein with partial occlusion or arterioportal shunts. 6. Six of 13 cases with occlusion of main portal vein showed cavernous transformation and they were noted as multiple small enhanced vascularities around the porta hepatis in the CT. According to the results, we conclude that CT is a useful modality to detect the changes of the portal veins in the patients of the hepatoma.

Computed tomographic evaluation of the portal vein in the hepatomas

International Nuclear Information System (INIS)

Lee, Kee Hyung; Lee, Seung Chul; Bae, Man Gil; Seo, Heung Suk; Kim, Soon Yong; Lee, Min Ho; Kee, Choon Suhk; Park, Kyung Nam

1986-01-01

Computed tomography and pornographic findings of 63 patients with hepatoma, undergone hepatic angiography and superior mesenteric pornography for evaluation of tumor and thrombosis of portal vein and determination of indication of transcatheter arterial embolization for palliative treatment of hepatoma from April, 85 to June, 86 in Hanyang university hospital, were reviewed. The results were as follows: 1. In 36 cases, portal vein thrombosis was detected during photography. Nineteen of 37 cases which revealed localized hepatoma in the right lobe of the liver showed portal vein thrombosis; 9 of 11 cases of the left lobe; 8 of 14 cases which were involved in entire liver revealed thrombosis. One case localized in the caudate lobe showed no evidence of invasion to portal vein. 2. Twenty-four of 34 cases with diffuse infiltrative hepatoma revealed portal vein thrombosis and the incidence of portal vein thrombosis in this type were higher than in the cases of the nodular type. 3. The portal vein thrombosis appeared as filling defects of low density in the lumen of the portal veins in CT and they did not reveal contrast enhancement. 4. CT revealed well the evidence of obstructions in the cases of portal vein thrombosis and the findings were well-corresponded to the findings of the superior mesenteric photography. 5. Five of the cases of the portal vein thrombosis were missed in the CT and the causes were considered as due to partial volume effect of enhanced portal vein with partial occlusion or arterioportal shunts. 6. Six of 13 cases with occlusion of main portal vein showed cavernous transformation and they were noted as multiple small enhanced vascularities around the porta hepatis in the CT. According to the results, we conclude that CT is a useful modality to detect the changes of the portal veins in the patients of the hepatoma.

Agonist-induced desensitization of adenylyl cyclase in Y1 adrenocortical tumor cells

International Nuclear Information System (INIS)

Olson, M.F.; Tsao, J.; Pon, D.J.; Schimmer, B.P.

1991-01-01

Y1 adrenocortical tumor cells (Y1DS) and Y1 mutants resistant to ACTH-induced desensitization of adenylyl cyclase (Y1DR) were transfected with a gene encoding the mouse beta 2-adrenergic receptor (beta 2-AR). Transfectants expressed beta 2-ARs that were able to stimulate adenylyl cyclase activity and steroid biosynthesis. These transfectants were used to explore the basis for the DR mutation in Y1 cells. The authors demonstrate that beta-adrenergic agonists desensitize the adenylyl cyclase system in transfected Y1DS cells whereas transfected Y1DR cells are resistant to desensitization by beta-adrenergic agonists. The fate of the beta 2-ARs during desensitization was evaluated by photoaffinity labelling with [125I]iodocyanopindolol diazerine. Desensitization of Y1DS transfectants was accompanied by a modest loss in receptor density that was insufficient to account for the complete loss of responsiveness to beta-adrenergic agonists. The extent of receptor loss induced by beta-adrenergic agonists in Y1DR transfectants exceeded that in the Y1DS transfectants indicating that the mutation which protects Y1DR cells from agonist-induced desensitization is prior to receptor down-regulation in the desensitization pathway. From these results we infer that ACTH and isoproterenol desensitize adenylyl cyclase by a common pathway and that receptor loss is not a major component of the desensitization process in these cells

Chicken type II collagen induced immune tolerance of mesenteric lymph node lymphocytes by enhancing beta2-adrenergic receptor desensitization in rats with collagen-induced arthritis.

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Zhao, Wei; Tong, Tong; Wang, Ling; Li, Pei-Pei; Chang, Yan; Zhang, Ling-Ling; Wei, Wei

2011-01-01

Chicken type II collagen (CCII) is a protein extracted from the cartilage of chicken breast and exhibits intriguing possibilities for the treatment of autoimmune diseases by inducing oral tolerance. In this study, we investigated the effects of CCII on inflammatory and immune responses to the mesenteric lymph node lymphocytes (MLNLs) and the mechanisms by which CCII regulates beta2-adrenergic receptor (beta2-AR) signal transduction in collagen-induced arthritis (CIA) rats. The onset of secondary arthritis in rats appeared around day 14 after injection of CCII emulsion. Remarkable secondary inflammatory response and lymphocytes proliferation were observed in CIA rats. The administration of CCII (10, 20, 40μgkg(-1)day(-1), days 15-22) could significantly reduce synovial hyperplasia, lymphatic follicle hyperplasia, inflammatory cells infiltration of MLNLs in CIA rats. CCII (10, 20, 40μgkg(-1)day(-1), days 15-22) restored the previously decreased level of cAMP of MLNLs of CIA rats. Meanwhile, CCII increased total protein expressions of beta2-AR, GRK2 and decreased that of beta-arrestin1, 2 of MLNLs in CIA rats but had an slight effect on GRK3. CCII further increased plasmatic protein expressions of GRK2, G(α)s and decreased that of beta-arrestin1, 2, beta2-AR, and increased membrane protein expressions of beta2-AR, GRK2, G(α)s and decreased that of beta-arrestin1, 2 of MLNLs in CIA rats. These results demonstrate that the mechanisms of CCII on beta2-AR desensitization and beta2-AR-AC-cAMP transmembrane signal transduction of MLNLs play crucial roles in pathogenesis of this disease. Copyright © 2010 Elsevier B.V. All rights reserved.

Overexpression of c-Jun contributes to sorafenib resistance in human hepatoma cell lines.

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Yuki Haga

Full Text Available Despite recent advances in treatment strategies, it is still difficult to cure patients with hepatocellular carcinoma (HCC. Sorafenib is the only approved multiple kinase inhibitor for systemic chemotherapy in patients with advanced HCC. The majority of advanced HCC patients are resistant to sorafenib. The mechanisms of sorafenib resistance are still unknown.The expression of molecules involved in the mitogen-activated protein kinase (MAPK signaling pathway in human hepatoma cell lines was examined in the presence or absence of sorafenib. Apoptosis of human hepatoma cells treated with sorafenib was investigated, and the expression of Jun proto-oncogene (c-Jun was measured.The expression and phosphorylation of c-Jun were enhanced in human hepatoma cell lines after treatment with sorafenib. Inhibiting c-Jun enhanced sorafenib-induced apoptosis. The overexpression of c-Jun impaired sorafenib-induced apoptosis. The expression of osteopontin, one of the established AP-1 target genes, was enhanced after treatment with sorafenib in human hepatoma cell lines.The protein c-Jun plays a role in sorafenib resistance in human hepatoma cell lines. The modulation and phosphorylation of c-Jun could be a new therapeutic option for enhancing responsiveness to sorafenib. Modulating c-Jun may be useful for certain HCC patients with sorafenib resistance.

Enhancement of 1,3-bis(2-chloroethyl)-1-nitrosourea resistance by gamma-irradiation or drug pretreatment in rat hepatoma cells

International Nuclear Information System (INIS)

Habraken, Y.; Laval, F.

1991-01-01

Treatment of rat hepatoma cells (H4 cells) with various DNA-damaging agents increases the number of O6-methylguanine-DNA-methyltransferase (transferase) molecules per cell. Because the cellular resistance to chloroethylnitrosoureas depends on the number of transferase molecules, we studied the influence of pretreatment with gamma-irradiation, cis-dichlorodiammineplatinum(II), or 2-methyl-9-hydroxyellipticinium on the sensitivity of H4 cells to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The BCNU resistance depends on the gamma-ray dose and increases with time after irradiation: it is maximum when the drug is added 48 h after irradiation, which corresponds to the maximum enhancement of the transferase activity in the cells. Pretreatment with a single dose of cis-dichlorodiammineplatinum(II) or 2-methyl-9-hydroxyellipticinium also increases the cellular resistance to BCNU. This resistance is not due to a modification of the alkylation of the cellular DNA in the pretreated cells but is related to the increased transferase activity, as it is no longer observed when this activity is depleted by incubating the pretreated cells with the free base O6-methylguanine before BCNU treatment. These results suggest that tumor cells surviving after gamma-irradiation or drug treatment may become resistant to chemotherapy with chloroethylnitrosoureas

Performing Aspirin Desensitization in Aspirin-Exacerbated Respiratory Disease.

Science.gov (United States)

Waldram, Jeremy D; Simon, Ronald A

2016-11-01

Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic rhinosinusitis with nasal polyps, asthma, and reactions to cyclooxygenase-1-inhibiting drugs. This condition is often refractory to standard medical treatments and results in aggressive nasal polyposis that often requires multiple sinus surgeries. Aspirin desensitization followed by daily aspirin therapy is an important treatment option, and its efficacy has been validated in multiple research studies. Aspirin desensitization is not without risk, but specific protocols and recommendations exist to mitigate the risk. Most patients with AERD can undergo aspirin desensitization in an outpatient setting under the supervision of an allergist. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-term sinonasal outcomes of aspirin desensitization in aspirin exacerbated respiratory disease.

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Cho, Kyu-Sup; Soudry, Ethan; Psaltis, Alkis J; Nadeau, Kari C; McGhee, Sean A; Nayak, Jayakar V; Hwang, Peter H

2014-10-01

This study aimed to assess sinonasal outcomes in patients with aspirin exacerbated respiratory disease (AERD) undergoing aspirin desensitization following endoscopic sinus surgery (ESS). Case series with chart review. University hospital. A retrospective review of sinonasal outcomes was conducted for 30 AERD patients undergoing aspirin desensitization and maintenance therapy following ESS. Sinonasal outcomes were prospectively assessed by the Sinonasal Outcomes Test-22 (SNOT-22) and endoscopic polyp grading system. Data were collected preoperatively, 1 and 4 weeks postsurgery (before desensitization), and 1, 6, 12, 18, 24, and 30 months after aspirin desensitization. Twenty-eight of 30 patients (93.3%) successfully completed aspirin desensitization, whereas 2 of 30 (6.7%) were unable to complete desensitization due to respiratory intolerance. Of the 21 patients who successfully completed a minimum of 24 weeks of follow-up, 20 (95.2%) patients demonstrated sustained endoscopic and symptomatic improvement for a median follow-up period of 33 months. After surgical treatment but before desensitization, patients experienced significant reductions in SNOT-22 and polyp grade scores. In the first 6 months after aspirin desensitization, patients experienced further significant reductions in SNOT-22 scores, whereas polyp grade remained stable. The improvements in symptom endoscopic scores were preserved throughout the follow-up period after desensitization. No patients required additional sinus surgery. One patient had to discontinue aspirin therapy due to gastrointestinal side effects. No other adverse reactions to aspirin were noted. Aspirin desensitization following ESS appears to be a well-tolerated and effective adjunctive therapy for long-term control of nasal polyposis in patients with AERD. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Progress in Desensitization of the Highly HLA Sensitized Patient.

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Jordan, S C; Choi, J; Kahwaji, J; Vo, A

2016-04-01

The presence of HLA antibodies remains a significant and often impenetrable barrier to kidney transplantation, leading to increased morbidity and mortality for patients remaining on long-term dialysis. In recent years, a number of new approaches have been developed to overcome these barriers. Intravenous immunoglobulin (IVIG) remains the lynchpin of HLA desensitization therapy and has been shown in a prospective, randomized, placebo-controlled trial to improve transplantation rates. In addition, IVIG used in low doses with plasma exchange is a reliable protocol for desensitization. Another significant advancement was the addition of rituximab (anti-B-cell therapy) to IVIG and plasma exchange-based desensitization. This approach has significantly improved rates of transplantation and outcomes. There is limited experience with bortezomib (anti-plasma cell therapy) and eculizumab (complement inhibition) for desensitization. However, recent data from a completed trial of eculizumab failed to show a significant benefit for prevention of antibody-mediated rejection compared with standard therapy plus placebo, and bortezomib produced inconsistent results. There is a growing interest in developing new therapeutic agents for desensitization. Newer approaches that address antibody reduction with B-cell depletion are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

DESENSITIZATION PROPERTIES OF P2X3 RECEPTORS SHAPING PAIN SIGNALLING

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Rashid eGiniatullin

2013-12-01

Full Text Available ATP-gated P2X3 receptors are mostly expressed by nociceptive sensory neurons and participate in transduction of pain signals. P2X3 receptors show a combination of fast desensitization onset and slow recovery. Moreover, even low nanomolar agonist concentrations unable to evoke a response, can induce desensitization via a phenomenon called ‘high affinity desensitization’. We have also observed that recovery from desensitization is agonist-specific and can range from seconds to minutes. The recovery process displays unusually high temperature dependence. Likewise, recycling of P2X3 receptors in peri-membrane regions shows unexpectedly large temperature sensitivity. By applying kinetic modeling, we have previously shown that desensitization characteristics of P2X3 receptor are best explained with a cyclic model of receptor operation involving three agonist molecules binding a single receptor and that desensitization is primarily developing from the open receptor state. Mutagenesis experiments suggested that desensitization depends on a certain conformation of the ATP binding pocket and on the structure of the transmembrane domains forming the ion pore. Further molecular determinants of desensitization have been identified by mutating the intracellular N- and C-termini of P2X3 receptor. Unlike other P2X receptors, the P2X3 subtype is facilitated by extracellular calcium that acts via specific sites in the ectodomain neighboring the ATP binding pocket. Thus, substitution of serine275 in this region (called ‘left flipper’ converts the natural facilitation induced by extracellular calcium to receptor inhibition. Given such their strategic location in nociceptive neurons and unique desensitization properties, P2X3 receptors represent an attractive target for development of new analgesic drugs via promotion of desensitization aimed at suppressing chronic pain.

A case report of hepatoma with cystic calcification

Energy Technology Data Exchange (ETDEWEB)

Jeon, Byung Hee; Choi, Sung Wook; Kim, Byung So [Busan National University College of Medicine, Busan (Korea, Republic of)

1974-10-15

A case of hepatoma with cystic calcification radiographically which confirmed by pathological examination, was reported. The patients was 19 years old boy who had abdominal mass and pain in left upper quadrant for 1 month. His family history was not contributary. The upper G-I series revealed slight posterior displacement of the fundus with a cyst like calcification, about 4.5 X 5 cm, in diameter at the left upper quadrant. Liver scanning showed normal concentration of 198{sup A}u on the right lobe but nonvisualization of the left lobe area. Biopsy specimen showed hepatoma cells invading the portal vein and intrahepatic blood vessels, and the cystic structure which was a blood vessel invaded by the tumor consisting of the organized thrombi.

A Role for CD81 and Hepatitis C Virus in Hepatoma Mobility

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Claire L. Brimacombe

2014-03-01

Full Text Available Tetraspanins are a family of small proteins that interact with themselves, host transmembrane and cytosolic proteins to form tetraspanin enriched microdomains (TEMs that regulate important cellular functions. Several tetraspanin family members are linked to tumorigenesis. Hepatocellular carcinoma (HCC is an increasing global health burden, in part due to the increasing prevalence of hepatitis C virus (HCV associated HCC. The tetraspanin CD81 is an essential receptor for HCV, however, its role in hepatoma biology is uncertain. We demonstrate that antibody engagement of CD81 promotes hepatoma spread, which is limited by HCV infection, in an actin-dependent manner and identify an essential role for the C-terminal interaction with Ezrin-Radixin-Moesin (ERM proteins in this process. We show enhanced hepatoma migration and invasion following expression of CD81 and a reduction in invasive potential upon CD81 silencing. In addition, we reveal poorly differentiated HCC express significantly higher levels of CD81 compared to adjacent non-tumor tissue. In summary, these data support a role for CD81 in regulating hepatoma mobility and propose CD81 as a tumour promoter.

Insulin increases transcription of rat gene 33 through cis-acting elements in 5[prime]-flanking DNA

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Cadilla, C.; Isham, K.R.; Lee, K.L.; Ch' ang, L.Y.; Kenney, F.T. (Oak Ridge National Lab., TN (United States)); Johnson, A.C. (National Cancer Institute, Bethesda, MD (United States). Lab. of Molecular Biology)

1992-01-01

Gene 33 is a multihormonally-regulated rat gene whose transcription is rapidly and markedly enhanced by insulin in liver and cultured hepatoma cells. To examine the mechanism by which insulin regulates transcription, the authors have constructed chimeric plasmids in which expression of the bacterial cat gene, encoding chloramphenicol acetyltransferase (CAT), is governed by gene 33 promoter elements and contiguous sequence in DNA flanking the transcription start point (tsp). When transfected into H4IIE hepatoma cells, these constructs gave rise to stably transformed cell lines producing the bacterial CAT enzyme. This expression was increased by insulin treatment in a fashion resembling the effect of this hormone on transcription of the native gene. In vitro transcription assays in nuclear extracts also revealed increased transcription of the chimeric plasmids when the extracts were prepared from insulin-treated rat hepatoma cells. The results demonstrate that induction by insulin is mediated by cis-acting nucleotide sequences located between bp [minus]480 to +27 relative to the tsp.

Prostaglandin (PG) synthesis by hepatoma cells

International Nuclear Information System (INIS)

Cyran, J.; Lysz, T.W.; Lea, M.A.

1987-01-01

Proliferation of cultured HTC hepatoma cells was reported to be inhibited by indomethacin but synthesis of PG in these cells was no detected. The authors have found that omission of fetal calf serum from the medium permits detection of synthesis of 6-keto-PGF1 alpha, PFG2 alpha, PGE2 and TxB2 from labeled arachidonic acid. Two additional peaks were identified as metabolites of PGF2 alpha and PGE2 by retention times on HPLC. Indomethacin inhibited the formation of the PGs and the metabolites. When 3 H-PGE2 and 3 H-PGF2 alpha were added to the cultures, approximately 50% of the label was recovered as the PG metabolites after a 4 day incubation. Metabolism of 3 H-TxB2 was not detected. When HTC cells were grown in the presence of 100 μM flurbiprofen, a cyclooxygenase inhibitor, there was significant inhibition of both cell proliferation and 3 H-thymidine uptake. The authors data suggest that proliferation of hepatoma cells is facilitated by synthesis of PGs

Preliminary result in patients with primary hepatoma treated by stereotactic radiotherapy

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Kang, Ki Mun; Choi, Ihl Bohng; Kim, In Ah; Choi, Byung Ock; Kang, Young Nam; Han, Sung Tae; Chung, Gyu Won [College of Medicine, Catholic Univ., Seoul (Korea, Republic of); Chai, Gyu Young [College of Medicine, Gyeongsang National Univ., Chinju (Korea, Republic of)

2001-03-01

It is not common to evaluate the response of the fractionated stereotactic radiotherapy (SRT) to primary hepatoma as compared with conventional radiotherapy. The purpose of the study was to take the preliminary result on the clinical trial of primary hepatoma by SRT. From July 1999 to March 2000, thirty three patients were hospitalized in the St. Mary's Hospital, and treated with SRT for extracranial tumors. Among them, 13 patients were diagnosed to primary hepatoma and then applied by frameless SRT using 6 MV linac accelerator. There were 12 male and 1 female patients. They had the age of 44-66 year old (median: 59) and the tumor size of 10-825 cc (median: 185 cc). SRT was given to them 3-5 fractions a week (5 Gy/fraction, 90% isodose line) for 2-3 weeks. Median dose of SRT was 50 Gy and the range was 30-50 Gy. Follow-up period ranged from 3 months to 13 months with median of 8 months. After treating SRT to thirteen patients with primary hepatoma, the response of the tumor was examined by abdominal CT: they are classified by 1 complete regression (7.7%), 7 partial regression (53.8%), 4 minimal regression (30.8%), 1 stable disease (7.7%). The positive responses more than partial remission were 8 patients (61.5%) after the treatment. The level of serum alpha-fetoprotein (AFP) after the treatment as compared with pretreatment had been 92.3% decreased. There was no severe complication except dyspepsia 84.6%, mild nausea 69.2%, transient decreased of hepatic function 15.4% and fever 7.7%. SRT to the patients with primary hepatoma was potentially suggested to become the safe and more effective tool than the conventional radiotherapy even though there were relatively short duration of follow-up and small numbers to be tested.

Baicalein inhibits the migration and invasive properties of human hepatoma cells

International Nuclear Information System (INIS)

Chiu, Yung-Wei; Lin, Tseng-Hsi; Huang, Wen-Shih; Teng, Chun-Yuh; Liou, Yi-Sheng; Kuo, Wu-Hsien; Lin, Wea-Lung; Huang, Hai-I; Tung, Jai-Nien; Huang, Chih-Yang; Liu, Jer-Yuh; Wang, Wen-Hung; Hwang, Jin-Ming

2011-01-01

Flavonoids have been demonstrated to exert health benefits in humans. We investigated whether the flavonoid baicalein would inhibit the adhesion, migration, invasion, and growth of human hepatoma cell lines, and we also investigated its mechanism of action. The separate effects of baicalein and baicalin on the viability of HA22T/VGH and SK-Hep1 cells were investigated for 24 h. To evaluate their invasive properties, cells were incubated on matrigel-coated transwell membranes in the presence or absence of baicalein. We examined the effect of baicalein on the adhesion of cells, on the activation of matrix metalloproteinases (MMPs), protein kinase C (PKC), and p38 mitogen-activated protein kinase (MAPK), and on tumor growth in vivo. We observed that baicalein suppresses hepatoma cell growth by 55%, baicalein-treated cells showed lower levels of migration than untreated cells, and cell invasion was significantly reduced to 28%. Incubation of hepatoma cells with baicalein also significantly inhibited cell adhesion to matrigel, collagen I, and gelatin-coated substrate. Baicalein also decreased the gelatinolytic activities of the matrix metalloproteinases MMP-2, MMP-9, and uPA, decreased p50 and p65 nuclear translocation, and decreased phosphorylated I-kappa-B (IKB)-β. In addition, baicalein reduced the phosphorylation levels of PKCα and p38 proteins, which regulate invasion in poorly differentiated hepatoma cells. Finally, when SK-Hep1 cells were grown as xenografts in nude mice, intraperitoneal (i.p.) injection of baicalein induced a significant dose-dependent decrease in tumor growth. These results demonstrate the anticancer properties of baicalein, which include the inhibition of adhesion, invasion, migration, and proliferation of human hepatoma cells in vivo. - Highlight: → Baicalein inhibits several essential steps in the onset of metastasis.

Transfer, Behavioral Improvement, and Anxiety Reduction in Systematic Desensitization

Science.gov (United States)

Kennedy, Thomas D.; Kimura, Harry K.

1974-01-01

Degree of transfer and fear change associated with four levels of desensitization, pseudodesensitization, and no treatment were assessed in snakephobic students. Desensitization subjects reported significantly less anxiety than no-treatment controls when repeating their highest pretreatment responses, but were no different from either control…

Therapist Warmth: Necessary or Sufficient Condition in Behavioral Desensitization?

Science.gov (United States)

Wolowitz, Howard Martin

1975-01-01

Discusses the Morris and Suckerman report on experimental studies testing the Rogerian hypothesis that phobic desensitization occurs as a function of therapist warmth versus the behavioral explanation that desensitization is a function of reciprocal inhibition. Morris and Suckerman respond to the critique. (Author/EJT)

Effects of Modeling and Desensitation in Reducing Dentist Phobia

Science.gov (United States)

Shaw, David W.; Thoresen, Carl E.

1974-01-01

Many persons avoid dentists and dental work. The present study explored the effects of systematic desensitization and social-modeling treatments with placebo and assessment control groups. Modeling was more effective than desensitization as shown by the number of subjects who went to a dentist. (Author)

Safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease.

Science.gov (United States)

McMullan, Kathryn L; Wedner, H James

2013-01-01

Aspirin (ASA) is the drug of choice in patients with coronary artery disease for primary and secondary prevention. This poses a problem for those patients reporting hypersensitivity to this drug or class of drugs. Desensitization to ASA may be carried out safely and effectively in patients with reported ASA or nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity needing ASA for cardiac indications. Our 7-step protocol is one choice for a rapid desensitization protocol. A retrospective chart review was conducted evaluating ASA desensitization in patients with reported ASA or NSAID hypersensitivity and a cardiac indication for ASA. In 160 evaluations over 15 years, 89 desensitizations were performed in both the inpatient and outpatient setting with only 16 reactions (18%). Eleven of these 16 patients (68.7%) were able to take daily ASA. Twenty-six desensitization procedures were performed with our 7-step rapid desensitization protocol in 10 inpatients and 16 outpatients with 3 reactions (18.75% of reactions). Initial reaction to ASA involving angioedema and reacting to ASA within the past year increased the risk of having a reaction to desensitization. Desensitization may be safely performed in patients with reported ASA or NSAID hypersensitivity and a cardiac indication for ASA. Our 7-step rapid protocol may be used in both the inpatient and outpatient setting to desensitize these patients. Patients who had angioedema with ASA ingestion or a reaction to ASA within the past year are at higher risk for reaction during the desensitization protocol. The authors have no funding, financial relationships, or conflicts of interest to disclose. © 2012 Wiley Periodicals, Inc.

Cytokine expression before and after aspirin desensitization therapy in aspirin-exacerbated respiratory disease.

Science.gov (United States)

Aktas, Ayse; Kurt, Emel; Gulbas, Zafer

2013-12-01

Aspirin exacerbated respiratory disease (AERD) is induced by acetylsalicylic acid (ASA) and/or nonsteroidal antiinflammatory drugs (NSAIDs). Effects of desensitization on many mediators have been examined previously, but few studies addressed the influence of desensitization on T lymphocytes and T lymphocyte-derived cytokines. This study was performed to examine peripheral blood lymphocyte (PBL) cytokine expression in aspirin-sensitive patients who have asthma before and after aspirin desensitization. In this study, the release of interleukin-2 (IL-2), interleukin-4 (IL-4), and interferon-gamma (IFN-γ) by CD4+ T lymphocytes prior to aspirin desensitization were also measured at intracellular levels, and expression of these cytokines after 1 month aspirin desensitization was evaluated. Twelve patients with AERD were included in the study. Two different control groups were formed, one consisted of 15 healthy people and second 12 aspirin tolerant asthmatic (ATA) patients using aspirin. A blood sample was collected prior to desensitization, and the tests were repeated by taking a second blood sample 1 month after the 4-day desensitization treatment. The proportion of lymphocytes secreting IFN-γ in the study group was 15.61 ± 4.40 % before desensitization and 15.08 ± 5.89 % after desensitization. The rate of IFN-γ secreting CD4+ T lymphocytes was 20.51 ± 4.41 % in the normal control group and 16.07 ± 5.7 % in the ATA group (p = 0.021). The ratio of CD4+ T lymphocyte secreting IFN-γ was reduced in patients with AERD before desensitization compared to normal control group (p = 0.040). The levels of IL-2, IL-4, and the subsets of lymphocyte were not different before and after desensitization compared to control groups.

Linezolid desensitization for a patient with multiple medication hypersensitivity reactions.

Science.gov (United States)

Bagwell, Autumn D; Stollings, Joanna L; White, Katie D; Fadugba, Olajumoke O; Choi, Jane J

2013-01-01

To describe a case in which a linezolid desensitization protocol was successfully used for a polymicrobial surgical wound infection in a patient with multiple drug hypersensitivity reactions. A 24-year-old woman with vocal cord dysfunction requiring tracheostomy was admitted for a surgical wound infection following a tracheostomy fistula closure procedure. The patient reported multiple antibiotic allergies including penicillins (rash), sulfonamides (rash), vancomycin (anaphylaxis), azithromycin (rash), cephalosporins (anaphylaxis), levofloxacin (unspecified), clindamycin (unspecified), and carbapenems (unspecified). Gram stain of the purulent wound drainage demonstrated mixed gram-negative and gram-positive flora, and bacterial cultures were overgrown with Proteus mirabilis, which precluded identification of other pathogens. Following failed test doses of linezolid, tigecycline, and daptomycin, all of which resulted in hypersensitivity reactions, a 16-step linezolid desensitization protocol was developed and successfully implemented without adverse reactions. The patient completed a 2-week course of antibiotic therapy that included linezolid upon finishing the desensitization protocol. Linezolid is useful in treating complicated and uncomplicated skin and soft tissue infections caused by gram-positive bacteria. With precautions, including premedication, a monitored nursing unit, and immediate availability of an emergency anaphylaxis kit, drug desensitization allows patients the ability to safely use medications to which they may have an immediate hypersensitivity reaction. Minimal data exist on linezolid desensitization protocols. Linezolid desensitization can be a viable option in patients requiring antimicrobial therapy for complicated gram-positive skin infections.

Expression of 65-kDa oncofetal protein in experimental hepatoma after antivancer therapy

International Nuclear Information System (INIS)

Mirowski, M.; Rozalski, M.; Krajewska, U.; Wierbicki, R.; Hanausek, M.

1997-01-01

We have tested the expression of 65-kDa oncofetal protein (p65) after combined treatment with menadione and methotrexate in hamsters transplanted with Kirkman-Robbins hepatoma. The treatment of tumor-bearing animals with these compounds significantly inhibited both the tumor development and the expression of p65. This inhibition in tumor tissue was calculated from densitograms of Western blots. The inhibition of p65 was also confirmed in the serum of hepatoma bearing animals by using solid-phase radioimmunoassay (RIA) to quantify the specificity of polyclonal antibodies to fetal p65 molecules. Additionally, p65 was shown to localize both in cytoplasm an in the nuclear extracts prepared from hepatoma tissue. (author)

Galvanic Skin Response and Reported Anxiety During Systematic Desensitization

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Hyman, Edward T.; Gale, Elliot N.

1973-01-01

The purpose of the present study was to investigate the GSR during systematic desensitization. Three groups of females each were preselected for high snake fear. Outcome measures indicated that the desensitization group reduced phobic behavior most, followed by the relaxation group, and then the exposure groups. (Author)

Semantics Desensitization: A Paradigmatic Intervention Approach to Anxiety Disorders.

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Hekmat, Hamid; And Others

1984-01-01

Assigned speech-anxious clients (N=30) to one of the following treatment conditions: (1) semantic desensitization; (2) attention placebo and (3) waiting list control. Results indicated that semantic desensitization therapy reduced both the affective and behavioral components of anxiety as compared to the two controls. (LLL)

The concentration of cadmium in hepatoma among Filipinos

International Nuclear Information System (INIS)

Alejandrino, A.L.; Goze, C.B.; Paradero, R.R.

1977-08-01

The concentration of cadmium in liver hepatoma and in normal liver in Filipinos was determined by atomic absorption spectrophotometry. Using NBS Bovine Liver (SRM1577) as reference material, a value of 0.28+-0.025 ug/g dry weight was obtained for cadmium which is close to the certified NBS value of 0.27+-0.04 ug/g. The mean percentage recovery for cadmium determination by AAS was 98.38%. A mean value of 2.14+-1.58 ug Cd/g liver hepatoma was observed for the 12 cases investigated, showing decreased cadmium levels in the cancerous liver compared to the mean value of 12.62 ug Cd/g observed for normal liver obtained from 10 cases of accidental deaths. The values are expressed on a dry weight basis

[Adaptive desensitization for acetylsalicylic acid hypersensitivity: A success story?].

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Mühlmeier, G; Hausch, R; Maier, H

2015-10-01

Adaptive desensitization still remains the only causative therapy for acetylsalicylic acid (ASA) hypersensitivity and is carried out nearly worldwide. To date there are hardly any data available on disease development under current desensitization therapy and longitudinal data in particular are missing. Out of a large collective of patients with proven hypersensitivity to ASA, 194 patients with initiated desensitization treatment were observed for periods up to 5 years (average 32 months). Patients with immediate reactions to systemic challenge tests revealed a response rate of 77% after 12 months of therapy. In this period 12% reached complete remission, 38% showed a clear reduction in symptoms, 32% reached partial remission, 13% remained unchanged and 5% suffered from disease progression. Adaptive desensitization therapy for hypersensitivity to ASA has been shown to be an effective causative therapy and chronic hyperplastic sinusitis as well as bronchial asthma could be improved. For the determination of maintenance dosages and required time periods more data are needed.

[Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

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Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

2016-06-01

Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Response of Hepatoma 9618a and Normal Liver to Host Carbogen and Carbon Monoxide Breathing

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Simon P. Robinson

1999-12-01

Full Text Available The effects of hyperoxia (induced by host carbogen 95% oxygen/5% carbon dioxide breathing. and hypoxia (induced by host carbon monoxide CO at 660 ppm. breathing were compared by using noninvasive magnetic resonance (MR methods to gain simultaneous information on blood flow/oxygenation and the bioenergetic status of rat Morris H9618a hepatomas. Both carbogen and CO breathing induced a 1.5- to 2-fold increase in signal intensity in blood oxygenation level dependent (BOLD MR images. This was due to a decrease in deoxyhemoglobin (deoxyHb, which acts as an endogenous contrast agent, caused either by formation of oxyhemoglobin in the case of carbogen breathing, or carboxyhemoglobin with CO breathing. The results were confirmed by observation of similar changes in deoxyHb in arterial blood samples examined ex vivo after carbogen or CO breathing. There was no change in nucleoside triphosphates (NTP/PI in either tumor or liver after CO breathing, whereas NTP/Pl increased twofold in the hepatoma (but not in the liver after carbogen breathing. No changes in tumor intracellular pH were seen after either treatment, whereas extracellular pH became more alkaline after CO breathing and more acid after carbogen breathing, respectively. This tumor type and the liver are unaffected by CO breathing at 660 ppm, which implies an adequate oxygen supply.

Enhancement of acetylcholine-induced desensitization of guinea-pig ileal longitudinal muscle in Ca2+-free conditions.

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Horio, S; Nagare, T; Moritoki, H

1999-10-01

1. To determine the role of cellular Ca2+ in desensitization, acetylcholine(ACh)-induced desensitization was studied under Ca2+-free condition in guinea-pig ileal longitudinal muscle. 2. Pretreatment of the tissue with 10(-4) M ACh (desensitizing treatment) in normal Tyrode solution caused desensitization of the responses both to ACh and histamine. The desensitizing treatment performed in Ca2+-free solution enhanced desensitization of the responses to ACh and histamine significantly. 3. The desensitizing treatment with ACh caused suppression of the responses to high K+ (tonic component) and Bay K 8644. The desensitizing treatment performed in Ca2+-free solution potentiated the suppression of the responses to high K+ and Bay K 8644 significantly. 4. ACh-induced desensitization was enhanced significantly in the presence of a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine(H-7, 10(-4) M) to a similar extent as desensitization obtained under Ca2+-free condition, but not in the presence of a non-specific and less potent kinase inhibitor, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004, 10(-4) M). 5. These results suggested that voltage-gated Ca2+ channels were involved in ACh-induced desensitization and that intracellular Ca2+, which was increased during the stimulation with ACh, inhibited desensitization through the activation of protein kinase C. This kinase could have activated or protected Ca2+ channels during the desensitization process to reduce desensitization.

Uncoupling of the beta-adrenergic receptor as a mechanism of in vitro neutrophil desensitization

International Nuclear Information System (INIS)

Galant, S.P.; Britt, S.

1984-01-01

Human leukocytes have been useful in studying desensitization phenomena to beta-adrenergic agonists in a number of clinical conditions. In the present in vitro study the authors have explored the mechanism for beta-adrenergic desensitization and have compared conditions for homologous and heterologous desensitization, using the intact PMN model. PMN preincubated with isoproterenol (10 -4 M), washed thoroughly, then restimulated, desensitized rapidly so that within 10 min 80% of control isoproterenol-induced cyclic AMP stimulation is lost. Cells washed free of isoproterenol recover full responsiveness in 1 to 2 hr. The estimated isoproterenol desensitization EC 50 in cells washed and then restimulated is 1 x 10 -5 M, and EC 50 in unwashed cells that are restimulated is 9 x 10 -8 M. Rank-order potency studies of catecholamine desensitization show isoproterenol > epinephrine > norepinephrine, a beta-2 pattern. Isoproterenol-induced desensitization results in a small reduction in [ 3 H]DHA binding sites, which becomes statistically significant (p 50 of 6.6 +/- 2.6 x 10 - (M, which is significantly different (p 50 of 38.1 +/- 9.1 x 10 -1 M found when cells are previously desensitized with isoproterenol for 10 min. GTP does not affect the EC 50 of desensitized cells. Finally, prolonged (3 hr) isoproterenol preincubation results in a small but significant (p 1 (59.3% +/- 7.4), suggesting heterologous desensitization. These studies suggest that the human PMN is a suitable model to study both homologous and heterologous desensitization in vitro. 22 references. 6 figures. 3 tables

The role of aspirin desensitization in patients with aspirin-exacerbated respiratory disease (AERD).

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Spies, Jonas Willian; Valera, Fabiana Cardoso Pereira; Cordeiro, Daniel Loiola; de Mendonça, Taís Nociti; Leite, Marcelo Gonçalves Junqueira; Tamashiro, Edwin; Arruda, Luiza Karla; Anselmo-Lima, Wilma Terezinha

2016-01-01

Aspirin-exacerbated respiratory disease (AERD) consists of a classic tetrad: moderate/severe asthma, chronic rhinosinusitis, nasal polyps, and intolerance to aspirin or other nonsteroidal anti-inflammatory drugs. Clinical control with drugs, surgery, and desensitization are treatment options. To evaluate the efficacy and tolerability of aspirin desensitization in patients with AERD. Periodic symptom assessment and endoscopy in patients with AERD undergoing surgery who were desensitized. Seventeen patients were desensitized. Eight patients completed the desensitization and were followed for a minimum of a one-year period (mean 3.1 years). These patients showed improvement in all symptoms. Moreover, surgical reassessment was not indicated in any of these patients and there was a decrease in costs with medication and procedures. Eight patients did not complete desensitization, mainly due to procedure intolerance and uncontrolled asthma, whereas another patient was lost to follow-up. Aspirin desensitization, when tolerated, was effective in patients with AERD and with poor clinical/surgical response. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Effect of desensitizing agents on dentin permeability.

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Ishihata, Hiroshi; Kanehira, Masafumi; Nagai, Tomoko; Finger, Werner J; Shimauchi, Hidetoshi; Komatsu, Masashi

2009-06-01

To investigate the in vitro efficacy of two dentin desensitizing products at reducing liquid permeability through human dentin discs. The tested hypothesis was that the products, in spite of different chemical mechanisms were not different at reducing or eliminating flow through dentin discs. Dentin slices (1 mm thick) were prepared from 16 extracted human third molars and their permeability was indirectly recorded in a split chamber model, using a chemiluminescence technique, after EDTA treatment (control), after soaking with albumin, and after desensitizer application. Two products were studied: MS Coat, a self-curing resin-containing oxalate product, and Gluma Desensitizer, a glutaraldehyde/HEMA-based agent without initiator. The dentin slices were mounted between an upper chamber, filled with an aqueous solution of 1% potassium ferricyanide and 0.3% hydrogen peroxide, and a lower chamber filled with 1% sodium hydroxide solution and 0.02% luminol. The upper solution was pressurized, and upon contact with the luminol solution a photochemical signal was generated and recorded as a measure of permeability throughout two consecutive pressurizing cycles at 2.5 and 13 kPa (26 and 133 cm H2O), respectively. The permeability of the control and albumin-soaked samples was similarly high. After application of the desensitizing agents, dentin permeability was reduced to virtually zero at both pressure levels (P < 0.001).

Rapid polyclonal desensitization with antibodies to IgE and FcεRIα.

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Khodoun, Marat V; Kucuk, Zeynep Yesim; Strait, Richard T; Krishnamurthy, Durga; Janek, Kevin; Lewkowich, Ian; Morris, Suzanne C; Finkelman, Fred D

2013-06-01

Rapid desensitization, a procedure in which persons allergic to an antigen are treated at short intervals with increasing doses of that antigen until they tolerate a large dose, is an effective, but risky, way to induce temporary tolerance. We wanted to determine whether this approach can be adapted to suppress all IgE-mediated allergies in mice by injecting serially increasing doses of monoclonal antibodies (mAbs) to IgE or FcεRIα. Active and passive models of antigen- and anti-IgE mAb-induced IgE-mediated anaphylaxis were used. Mice were desensitized with serially increasing doses of anti-IgE mAb, anti-FcεRIα mAb, or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux, and changes in cell number and FcεRI and IgE expression were evaluated. Rapid desensitization with anti-IgE mAb suppressed IgE-mediated immediate hypersensitivity; however, some mice developed mild anaphylaxis during desensitization. Rapid desensitization with anti-FcεRIα mAb that only binds FcεRI that is not occupied by IgE suppressed both active and passive IgE-mediated anaphylaxis without inducing disease. It quickly, but temporarily, suppressed IgE-mediated anaphylaxis by decreasing mast cell signaling through FcεRI, then slowly induced longer lasting mast cell unresponsiveness by removing membrane FcεRI. Rapid desensitization with anti-FcεRIα mAb was safer and longer lasting than rapid desensitization with antigen. A rapid desensitization approach with anti-FcεRIα mAb safely desensitizes mice to IgE-mediated anaphylaxis by inducing mast cell anergy and later removing all mast cell IgE. Rapid desensitization with an anti-human FcεRIα mAb may be able to prevent human IgE-mediated anaphylaxis. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Outpatient desensitization in selected patients with platinum hypersensitivity reactions.

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O'Malley, David M; Vetter, Monica Hagan; Cohn, David E; Khan, Ambar; Hays, John L

2017-06-01

Platinum-based chemotherapies are a standard treatment for both initial and recurrent gynecologic cancers. Given this widespread use, it is important to be aware of the features of platinum hypersensitivity reactions and the subsequent treatment of these reactions. There is also increasing interest in the development of desensitization protocols to allow patients with a history of platinum hypersensitivity to receive further platinum based therapy. In this review, we describe the management of platinum hypersensitivity reactions and the desensitization protocols utilized at our institution. We also describe the clinical categorizations utilized to triage patients to appropriate desensitization protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

Growth characteristics and imaging properties of the morris hepatoma 3924a in ACI rats: A suitable model for transarterial chemoembolization

International Nuclear Information System (INIS)

Truebenbach, Jochen; Graepler, Florian; Pereira, Philippe L; Ruck, Peter; Lauer, Ulrich; Gregor, Michael; Claussen, Claus-D.; Huppert, Peter E.

2000-01-01

Purpose: For experimental studies investigating modalities and efficacy of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) an animal model resembling the human situation as closely as possible would be appropriate. Specifically, reproducible tumor growth characteristics with the capability for appropriate in vivo imaging to monitor treatment efficacy are required.Methods: Morris hepatoma 3924A was implanted into the liver of 30 ACI rats. Tumor growth was followed by angiography (n=10), ultrasound (US, n=30), native computed tomography (CT. n=16), and native magnetic resonance imaging (MRU n=30) between day 8 and day 36 after implantation. The radiological morphological characteristics were compared with the macroscopic and microscopic histological findings of the explanted tumors.Results: In all 30 animals a solitary liver tumor was found and macroscopically no signs of metastases, ascites, or peritoneal tumor were visible. On histopathological examination tumor sizes ranged between 27 ± 3 mm 3 (day 8) and 3468 ± 79 mm 3 (day 36). The first signs of tumor necrosis occurred at day 16. US allowed tumor visualization from day 8, MRI from day 8, angiography from day 10, and CT from day 14.Conclusions: The tumor model has the potential to be used for the visualization of tumor growth by MRI and US. The potential for monitoring therapeutic effects of TACE needs to be investigated.

Omalizumab facilitates rapid oral desensitization for peanut allergy.

Science.gov (United States)

MacGinnitie, Andrew J; Rachid, Rima; Gragg, Hana; Little, Sara V; Lakin, Paul; Cianferoni, Antonella; Heimall, Jennifer; Makhija, Melanie; Robison, Rachel; Chinthrajah, R Sharon; Lee, John; Lebovidge, Jennifer; Dominguez, Tina; Rooney, Courtney; Lewis, Megan Ott; Koss, Jennifer; Burke-Roberts, Elizabeth; Chin, Kimberly; Logvinenko, Tanya; Pongracic, Jacqueline A; Umetsu, Dale T; Spergel, Jonathan; Nadeau, Kari C; Schneider, Lynda C

2017-03-01

Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients. Thirty-seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P omalizumab versus 1 subject receiving placebo passed the 4000-mg food challenge. Overall reaction rates were not significantly lower in omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses. Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The involvement of splenic artery in the blood supply of hepatomas: its DSA findings and interventional treatment

International Nuclear Information System (INIS)

Duan Xuhua; Liang Huiming; Feng Gansheng; Zheng Chuangsheng; Ren Jianzhuang

2009-01-01

Objective: To investigate the DSA manifestations of the involvement of splenic artery in supplying blood to hepatomas and to assess the therapeutic value of super-selective interventional embolization. Methods: During the period of March 2005-June 2008, 897 patients with hepatoma underwent angiography and the involvement of splenic artery in the blood supply of hepatoma was confirmed in 7 cases. Splenic arteriography was performed by means of super-selective catheterization with 5 F Yashiro catheter together with 3 F SP catheter. The splenic arteries which supplied blood to hepatomas were embolized with hyper-liquid iodized-oil emulsion mixed with chemotherapy drug, which was followed by the injection of sufficient gelatin sponge or ethanol. The clinical results were analyzed. Results: Splenic arteriography revealed that the splenic artery was the main supplying vessel of the hepatoma in two cases, and was not the main supplying vessel of the hepatoma in five cases. The splenic supplying vessels were completely embolized in all 7 cases. After the procedure, AFP level was decreased over 50%, and in two patients it dropped to normal. CT checkup 4-6 weeks after the surgery revealed that the diameter of tumor decreased to 2.5 - 4.6 cm. Conclusion: The involvement of splenic artery in supplying blood to hepatomas is not common. Super-selective catheterization and sufficient embolization of the splenic supplying vessels are very important for improving the interventional effectiveness. (authors)

Diagnosis of hepatoma using grayscale and Doppler ultrasound in patients with chronic liver disease

Directory of Open Access Journals (Sweden)

Idris S

2011-10-01

Full Text Available Wasim A Memon, Zishan Haider, Mirza Amanullah Beg, Muhammad Idris, Tanveer-ul-Haq, Waseem Akhtar, Sidra IdrisRadiology Department, Aga Khan University Hospital, Karachi, Pakistan Every author contributed equally to the workObjective: To determine the diagnostic accuracy of liver ultrasound for the detection of hepatoma in chronic liver disease (CLD patients by either taking histopathology or serum α-fetoprotein levels or a biphasic computed tomography (CT scan (whichever is available as the gold standard.Study design: Cross-sectional.Place and duration of study: Radiology Department, The Aga Khan University Hospital, Karachi, Pakistan, from January 2007 to January 2010.Methods: A total of 239 patients (156 males and 83 females with clinical suspicion or surveillance of hepatoma in CLD referred to the radiology department for ultrasound evaluation followed by either liver biopsy and histopathology or serum α-fetoprotein level or biphasic CT scan.Results: The sensitivity of ultrasound for hepatoma detection in CLD was 65%, specificity was 85%, and accuracy was 70%, and positive predictive value and negative predictive value were 92% and 45%, respectively.Conclusion: Ultrasound is a relatively quick, safe, reasonably accurate, and noninvasive imaging modality for the detection of hepatoma in CLD and can be complemented with clinical assessment of screening high-risk patients.Keywords: hepatoma, ultrasound, radiology, chronic liver disease

Increased PRPP synthetase activity in cultured rat hepatoma cells containing mutations in the hypoxanthine-guanine phosphoribosyltransferase gene.

Science.gov (United States)

Graf, L H; McRoberts, J A; Harrison, T M; Martin, D W

1976-07-01

Nine independently derived clones of mutagenized rat hepatoma cells selected for resistance to 6-mercaptopurine (6-MP) or 6-thioguanine (6-ThioG) have been isolated. Each has severely reduced catalytic activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and seven of them possess significantly increased activities of phosphoribosylpyrophosphate (PRPP) synthetase. The degrees of elevations of PRPP synthetase activities do not correlate with the degrees of deficiencies of HPRT activities. The cells from one of these clones, 1020/12, posses 40% of the normal HPRT catalytic activity and overproduce purines. We have extensively examined the cells from this clone. Immunotration studies of 1020/12 cells indicate that there is a mutation in the structural gene for HPRT. Although they possess increased specific catalytic activities of the enzyme. PRPP synthetase, the catalytic parameters, heat stability, and isoelectric pH of PRPP synthetase from 1020/12 cells are indistinguishable from those of the enzyme from wild-type cells. The cause of purine overproduction by 1020/12 cells appears to be the elevated PRPP synthetase activity, rather than a PRPP "sparing" effect stemming from reduced HPRT activity. Support for this idea is provided by the observation that the complete loss of HPRT activity in a clone derived from 1020/12 cells does not further enhance the levels of PRPP synthetase or purine overproduction. We propose that the elevated levels of PRPP synthetase activity in these HPRT deficient cells result from a mutational event in the structural gene for HPRT, and that this causes the disruption of a previously undescribed regulatory function of this gene on the expression of the PRPP synthetase gene.

Aspirin desensitization in patients undergoing percutaneous coronary intervention: a survey of current practice.

Science.gov (United States)

Chapman, Andrew R; Rushworth, Gordon F; Leslie, Stephen J

2013-01-01

Aspirin remains the mainstay of anti-platelet therapy in cardiac patients. However, if a patient is allergic to aspirin and dual anti-platelet therapy is indicated - such as with percutaneous coronary intervention (PCI), then there is no clear guidance. One possibility is aspirin desensitization. A variety of protocols exist for the rapid desensitization of patients with aspirin allergy. The aim of this survey was to assess current knowledge and practice regarding aspirin desensitization in the UK. We conducted a UK wide survey of all UK 116 PCI centers and obtained complete responses from 40 (35.4%) centers. Of these, just 7 (17.5%) centers had previously desensitised patients; 29 (87.9%) centers suggested a lack of a local protocol prevented them from desensitizing, with 10 (30.3%) unsure of how to conduct desensitization. Only 5 (12.5%) centers had a local policy for aspirin desensitization although 25 (64.1%) units had a clinical strategy for dealing with aspirin allergy; the majority (72%) giving higher doses of thienopyridine class drugs. In the UK, there appears to be no consistent approach to patients with aspirin allergy. Patients undergoing PCI benefit from dual anti-platelet therapy (including aspirin), and aspirin desensitization in those with known allergy may facilitate this. Sustained effort should be placed on encouraging UK centers to use desensitization as a treatment modality prior to PCI rather than avoiding aspirin altogether.

A practical and successful desensitization protocol for immediate hypersensitivity reactions to iron salts.

Science.gov (United States)

Demir, Semra; Olgac, Muge; Unal, Derya; Gelincik, Asli; Colakoglu, Bahauddin; Buyukozturk, Suna

2014-01-01

Orally administered iron salts (OAS) are widely used in the management of iron deficiency anemia and hypersensitivity reactions to OAS are not common. If an offending drug is the sole option or is significantly more effective than its alternatives, it can be readministered by desensitization. The oral desensitization protocols for iron published so far concern either desensitization that was completed only over a long period or did not attain the recommended therapeutic dose. We aimed to develop a more effective protocol. We report here on 2 patients who experienced hypersensitivity reactions to OAS. After confirming the diagnosis, both patients were desensitized to oral ferrous (II) glycine sulfate complex according to a 2-day desensitization protocol. A commercial suspension of oral ferrous glycine sulfate, which contains 4 mg of elemental iron in 1 ml, was preferred. We started with a dose as low as 0.1 ml from a 1/100 dilution (0.004 mg elemental iron) of the original suspension and reached the maximum effective dose in 2 days. Both patients were successfully desensitized and they went on to complete the 6-month iron treatment without any adverse effects. Although hypersensitvity reactions to iron are not common, there is no alternative for iron administration. Therefore, desensitization has to be the choice. This easy desensitization protocol seems to be a promising option. © 2014 S. Karger AG, Basel.

Evaluation of XHVRB for Capturing Explosive Shock Desensitization

Science.gov (United States)

Tuttle, Leah; Schmitt, Robert; Kittell, Dave; Harstad, Eric

2017-06-01

Explosive shock desensitization phenomena have been recognized for some time. It has been demonstrated that pressure-based reactive flow models do not adequately capture the basic nature of the explosive behavior. Historically, replacing the local pressure with a shock captured pressure has dramatically improved the numerical modeling approaches. Models based upon shock pressure or functions of entropy have recently been developed. A pseudo-entropy based formulation using the History Variable Reactive Burn model, as proposed by Starkenberg, was implemented into the Eulerian shock physics code CTH. Improvements in the shock capturing algorithm were made. The model is demonstrated to reproduce single shock behavior consistent with published pop plot data. It is also demonstrated to capture a desensitization effect based on available literature data, and to qualitatively capture dead zones from desensitization in 2D corner turning experiments. This models shows promise for use in modeling and simulation problems that are relevant to the desensitization phenomena. Issues are identified with the current implementation and future work is proposed for improving and expanding model capabilities. Sandia National Laboratories is a multi-mission laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. DOE's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Pitocin and autism: An analysis of oxytocin receptor desensitization in the fetus.

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Gottlieb, Mark M

2016-02-01

The risk of Pitocin as a cause of autism attributable to oxytocin receptor desensitization in the brain of the fetus is evaluated in terms of a mathematical model. A composite unit, D, for oxytocin receptor desensitization levels is established with the form ((IU-h)/ml)E-3, where IU is the international unit for oxytocin. The desensitization values for oxytocin receptor desensitization at a concentration of 10 nmol of oxytocin per liter for 3, 4.2 and 6h corresponding to 0%, 50% and 100% desensitization are calculated to be 15 D, 21 D, and 30 D, respectively. The permeability of the blood-brain barrier in the fetus to oxytocin is discussed, and the upper limit of the concentration of Pitocin in the placenta, and its possible diffusion into the blood and brain of the fetus, is calculated for a routine dose of 6 milli U per minute of Pitocin over a 12h labor. This dose of Pitocin is shown to result in a desensitization value in units of D that is more than a factor of 10 below the 0% desensitization value of 15 D. This indicates that routine doses of Pitocin are not a significant cause of autism attributable to oxytocin receptor desensitization. This is consistent with the findings of a major epidemiological study of the association of Pitocin with autism in Denmark entitled, "Oxytocin-augmented labor and risk for males", Behavioral Brain Research, May 1, 2015; 284:207-212, which found no association between the use of Pitocin during labor and the incidence of autism for females, and a modest association for males. Copyright © 2015 Elsevier B.V. All rights reserved.

Drug desensitization in the management of hypersensitivity reactions to monoclonal antibodies and chemotherapy.

Science.gov (United States)

Mezzano, Veronica; Giavina-Bianchi, Pedro; Picard, Matthieu; Caiado, Joana; Castells, Mariana

2014-04-01

Hypersensitivity reactions to monoclonal antibodies and chemotherapy, which may vary in severity from mild to life-threatening, can lead to their discontinuation and replacement by alternative agents that are often less effective, more toxic, and/or more expensive. Drug desensitization has emerged as the best treatment modality capable of allowing re-introduction of the hypersensitivity reaction-inducing medication in highly sensitized patients in need of first line therapies. In recent years, the availability of new anti-neoplastic drugs and therapeutic monoclonal antibodies has increased, as has the potential for hypersensitivity reactions. Development of desensitization protocols for these new medications requires a careful assessment of the potential risks and benefits. The purposes of this review are to provide an overview of the presentation of hypersensitivity reactions amenable to desensitization and to increase awareness of the indications for and outcomes of desensitization protocols. Rapid drug desensitization has proven to be a safe and effective way of administering first line therapy to patients with hypersensitivity reactions, providing an extremely powerful treatment modality for patients for whom alternative drugs are deemed unacceptable. Rapid drug desensitization protocols should be administered only by highly trained allergists and nurses who have experience in determining which reactions are amenable to desensitization, and can identify high risk patients and provide them with appropriate care. Efforts should be made to increase awareness of the remarkable safety and efficacy of rapid drug desensitization among non-allergists, especially in the fields of oncology and rheumatology, so as to favor its universal application. Development of desensitization units to provide state-of-the-art care is possible only through coordinated teamwork.

EMG Biofeedback Training Versus Systematic Desensitization for Test Anxiety Reduction

Science.gov (United States)

Romano, John L.; Cabianca, William A.

1978-01-01

Biofeedback training to reduce test anxiety among university students was investigated. Biofeedback training with systematic desensitization was compared to an automated systematic desensitization program not using EMG feedback. Biofeedback training is a useful technique for reducing test anxiety, but not necessarily more effective than systematic…

Aplikasi eye moving desensitization dan reprocessing dalam konseling post-traumatic stress disorder

Directory of Open Access Journals (Sweden)

Hengki Satrianta

2017-06-01

Full Text Available Akhir-akhir ini banyak peristiwa yang berpotensi memunculkan efek traumatik yang jika tidak ditangani akan menimbulkan gangguan stres pascatrauma. Olehnya itu, dibutuhkan upaya-upaya untu menangani masalah ini. Salah satu upaya yang dimaksud adalah penggunaan eye moving desensitization and reprocessing. Artikel ini ditulis dengan fokus pada penanganan gangguan stres pascatrauma melalui eye moving desensitization and reprocessing. Tujuan penulisan artikel ini adalah untuk mengetahui gambaran umum pelaksanaan eye moving desensitization and reprocessing. Eye moving desensitization and reprocessing mampu menjadi salah satu teknik dalam penanganan gangguan stres pascatrauma. Oleh karena itu disarankan bagi praktisi konseling di Indonesia mampu menjadikan “terapi unik” ini sebagai teknik penanganan gangguan stres pascatrauma.

Successful drug desensitization in patients with delayed-type allergic reactions to anti-tuberculosis drugs

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Krittaecho Siripassorn

2018-03-01

Full Text Available Objective: To evaluate the outcomes of anti-tuberculosis drug desensitization. Methods: This was a retrospective study. Inclusion criteria were as follows: age >18 years, documented tuberculosis infection, a previous cutaneous allergic reaction to anti-tuberculosis drugs, and having undergone drug desensitization between January 2003 and March 2014. The definition of allergic reaction to anti-tuberculosis drugs included (1 a temporal relationship between drug use and the allergic reaction; (2 improvement in the allergic reaction after drug withdrawal; (3 recurrence of the allergic reaction after reintroduction of only the offending drug; and (4 absence of other causes. Results: A total of 19 desensitization procedures were performed. The drugs used for these procedures were isoniazid (n = 7, rifampicin (n = 6, or ethambutol (n = 6. Of note, severe allergic reactions (Stevens–Johnson syndrome (n = 4, erythema multiforme (n = 3, and drug rash with eosinophilia and systemic syndrome (n = 1 were included. All patients underwent resolution of the previous allergic reactions before desensitization. The median duration of desensitization was 18 days. The success rate was 78.9%. The allergic reactions following failed desensitization were not severe; most were maculopapular rashes. Conclusions: The desensitization protocol for anti-tuberculosis drugs was associated with a high success rate, and the individuals who failed desensitization experienced mild allergic reactions. Keywords: Desensitization, Antituberculosis, Steven-Johnson syndrome, Allergic drug reaction, Tolerance induction, Drug allergy

Anorexia‐cachexia syndrome in hepatoma tumour‐bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC‐1/GDF15

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Borner, Tito; Arnold, Myrtha; Ruud, Johan; Breit, Samuel N.; Langhans, Wolfgang; Lutz, Thomas A.; Blomqvist, Anders

2016-01-01

Abstract Background The cancer‐anorexia‐cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators and tumour‐derived factors are thought to play an important role in the aetiology of CACS. However, the central and peripheral mechanisms contributing to CACS are insufficiently understood. The area postrema (AP) and the nucleus tractus solitarii are two important brainstem centres for the control of eating during acute sickness conditions. Recently, the tumour‐derived macrophage inhibitory cytokine‐1 (MIC‐1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC‐1 in mice. Methods Using a rat hepatoma tumour model, we examined the roles of the AP and of vagal afferents in the mediation of CACS. Specifically, we investigated whether a lesion of the AP (APX) or subdiaphragmatic vagal deafferentation (SDA) attenuate anorexia, body weight, muscle, and fat loss. Moreover, we analysed MIC‐1 levels in this tumour model and their correlation with tumour size and the severity of the anorectic response. Results In tumour‐bearing sham‐operated animals mean daily food intake significantly decreased. The anorectic response was paralleled by a significant loss of body weight and muscle mass. APX rats were protected against anorexia, body weight loss, and muscle atrophy after tumour induction. In contrast, subdiaphragmatic vagal deafferentation did not attenuate cancer‐induced anorexia or body weight loss. Tumour‐bearing rats had substantially increased MIC‐1 levels, which positively correlated with tumour size and cancer progression and negatively correlated with food intake. Conclusions These findings demonstrate the importance of the AP in the mediation of cancer‐dependent anorexia and body weight loss and support a pathological role of MIC‐1 as a tumour‐derived factor mediating CACS, possibly via an AP�

Hypnosis Versus Systematic Desensitization in the Treatment of Test Anxiety

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Melnick, Joseph; Russell, Ronald W.

1976-01-01

This study compared the effectiveness of systematic desensitization and the directed experience hypnotic technique in reducing self-reported test anxiety and increasing the academic performance of test-anxious undergraduates (N=36). The results are discussed as evidence for systematic desensitization as the more effective treatment in reducing…

Desensitization to Mycofenolate Mofetil: a novel 12 step protocol.

Science.gov (United States)

Smith, M; Gonzalez-Estrada, A; Fernandez, J; Subramanian, A

2016-07-01

The use of MMF has become standard practice in many solid organ transplant recipients due its efficacy and favorable risk profile compared to other immunosuppressants. There has been a single case report of successful MMF desensitization. However, this protocol did not follow current Drug practice parameters. We report a successful desensitization to MMF in a double heart-kidney transplant recipient.

Desensitization of delayed-type hypersensitivity in mice: suppressive environment

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Takashi Katsura

1993-01-01

Full Text Available The systemic injection of high doses of antigen into a preimmunized animal results in transient unresponsiveness of cell-mediated immune responses. This phenomenon is known as desensitization. Serum interleukin 2 (IL-2 activity was found transiently in desensitized mice at 3 h after the antigen challenge. These mice could not reveal antigen nonspecific delayed-type hypersensitivity (DTH 1 d after the challenge. Specific suppression of DTH was observed at later stages. Sera from 3 h desensitized mice showed suppressive effects on DTH in preo immunized mice. Administration of recombinant IL-2 into preimmunized mice led to the failure of development of DTH to antigens. These observations suggest that IL-2 plays an important role in the suppressive environment.

Relationship between P53 and bystander effect induced by radiated hepatoma cells

International Nuclear Information System (INIS)

Zhao Meijia; Shen Bo; Yuan Dexiao; Cheng Honghong; Shao Chunlin

2009-01-01

The role of p53 in bystander responses on normal liver cells were investigated by co-culturing irradiated hepatoma cells with non-irradiated bystander Chang liver cells. It was found that radiosensitivity of the hepatoma cells was relative to p53. HepG2 cells with wtp53 had the highest radiosensitivity followed by PLC/PRF/5 cells with mtp53 and Hep3B cells with null-p53. The induction of bystander micronucleus(MN) was observed only in the Chang liver cells that had been co-cultured with HepG2 cells but not co-cultured with PLC/PRF/5 or Hep3B. Also, this bystander MN was relative to the irradiation dose and the cell co-culture rime. When the hepatoma cells were treated with pifithrin-α, a p53 inhibitor, their radiosensitivities were reduced, and the bystander effect was diminished. The results indicate that p53 could regulate not only the radiosensitivity but also the bystander response. (authors)

A successful desensitization protocol for horse-derived antithymocyte globulin in severe aplastic anemia.

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Demir, Esen; Cigerci Günaydın, Nurşen; Karadaş, Nihal; Gülen, Figen; Tanac, Remziye; Yılmaz, Deniz

2015-03-01

Horse antithymocyte globulin (h-ATG) (ATGAM(®) ) is the first choice of treatment in very severe patients with aplastic anemia who do not have any HLA matched sibling donor. h-ATG is a heterologous serum that may cause anaphylaxis. Alternative treatment strategies must be planned in case of hypersensitivity. Desensitization must be considered in patients without an alternative treatment of choice. We aimed to present the h-ATG desensitization protocol and consider its effectiveness in patients with aplastic anemia who are hypersensitized with h-ATG and do not have an alternative treatment of choice. Skin prick tests were performed with non-diluted solution in eight very severe patients with aplastic anemia who are followed up in Ege University Children's Hospital. Although skin prick test was found negative in these eight patients, different dilution h-ATG intradermal tests were performed and found positive in all patients. h-ATG desensitization program was started to these hypersensitized patients. Desensitization program was started to six male and two female very severe patients with aplastic anemia whose ages were between seven and 19 yr (median: 12.9 yr). All of the patients completed the desensitization program. While local reaction was seen in two patients, systemic reaction was seen in one patient and late reaction was seen in one patient during and after desensitization program. A successful desensitization program with h-ATG in children with aplastic anemia is presented. Even though there is not an exposure before to such high allergy potential heterologous serum, skin tests should be performed and desensitization must be started to patients who are hypersensitized to h-ATG. As the expected effectiveness of the treatment is so much, the desensitization protocol can be carried out safely and effectively with trained stuff although allergic reactions can be seen. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anxiety Management Training and Self-Control Desensitization: 15 Months Later.

Science.gov (United States)

Deffenbacher, Jerry L.; Michaels, Ann C.

1981-01-01

A 15-month follow-up study found that anxiety management training and self-control desensitization groups continued to report significantly less debilitating test anxiety than the control group. Anxiety management training and self-control desensitization groups also reported significantly less nontargeted anxiety than controls on both measures of…

RF and dc desensitized electroexplosive device

Science.gov (United States)

Krainiak, John W.; Speaks, Paul D.; Cornett, Michael S.

1989-07-01

This patent application relates to electroexplosive devices (EEDs) such as detonators, blasting caps and squibs, in particular to a method and device for desensitizing EEDs to electromagnetic radiation and electrostatic charges with the added ability to desensitize the device to essentially dc currents. An insensitive electroexplosive device to electrically ignite explosive is disclosed. This device is inherently immune to radio frequency (RF) radiation, and also provides protection against dc or very low frequency RF induced by arcing. A central feature is use of zeners and capacitors to form a reactively balanced bridge circuit. When constructed in semiconductor form, as described in this application, the device is capable of incorporation in small caliber ordnance.

A Controlled Study to Assess the Clinical Efficacy of Totally Self-Administered Systematic Desensitization

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Rosen, Gerald M.; And Others

1976-01-01

Highly anxious self-referred snake phobics received either (a) therapist-administered desensitization, (b) self-administered desensitization with weekly therapist phone calls, (c) totally self-administered desensitization, (d) self-administered double-blind placebo control, or (e) no treatment. Pretreatment to posttreatment measures revealed…

Magnetic nanoparticles for targeted therapeutic gene delivery and magnetic-inducing heating on hepatoma

International Nuclear Information System (INIS)

Yuan, Chenyan; Zhang, Jia; Li, Hongbo; Zhang, Hao; Wang, Ling; Zhang, Dongsheng; An, Yanli

2014-01-01

Gene therapy holds great promise for treating cancers, but their clinical applications are being hampered due to uncontrolled gene delivery and expression. To develop a targeted, safe and efficient tumor therapy system, we constructed a tissue-specific suicide gene delivery system by using magnetic nanoparticles (MNPs) as carriers for the combination of gene therapy and hyperthermia on hepatoma. The suicide gene was hepatoma-targeted and hypoxia-enhanced, and the MNPs possessed the ability to elevate temperature to the effective range for tumor hyperthermia as imposed on an alternating magnetic field (AMF). The tumoricidal effects of targeted gene therapy associated with hyperthermia were evaluated in vitro and in vivo. The experiment demonstrated that hyperthermia combined with a targeted gene therapy system proffer an effective tool for tumor therapy with high selectivity and the synergistic effect of hepatoma suppression. (paper)

Exposure to Violence and Children's Desensitization Attitudes in Lebanon.

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Tarabah, Asma; Badr, Lina Kurdahi; Usta, Jinan; Doyle, John

2016-11-01

Children exposed to multiple sources of violence may become desensitized, increasing the possibility of them imitating the aggressive behaviors they watch and considering such behavior as normal. The purpose of this article is to assess the association between exposure to various types of violence (including war) and desensitization in Lebanese children. A cross-sectional design with 207 school-aged children assessed exposure to violence using three surveys: (a) violence in the media (the Media Preference survey), (b) exposure to violence (the KID-SAVE survey), and (c) desensitization attitudes (the Attitude Toward Violence-Child Version). Children were between 8 and 12 years old, 56% were males, and 70%were from middle socioeconomic status (SES) backgrounds. Seventy-six percent of children reported being exposed to violence, with more exposure in males and in the lower SES group. Impact, however, was greater on girls. The predictors of attitude toward violence were "Frequency" of exposure, "Impact" of exposure, and the amount of violence viewed on television. Children are massively exposed to violence in Lebanon resulting in desensitization, which may habituate them to accept violence as normal and put them at risk for imitating violent behaviors. © The Author(s) 2015.

Desensitization of stainless steels by laser surface heat-treatment

Energy Technology Data Exchange (ETDEWEB)

Nakao, Yoshikuni; Nishimoto, Kazutoshi

1987-11-01

Laser heating was applied for the desensitization heat-treatment of the surface layer in the sensitized HAZ of Type 304 stainless steel. The degree of sensitization was examined by EPR technique and the 10 % oxalic acid electrolytic etch test. The CO/sub 2/ laser with maximum power of 1.5 kW was used for heat-treatment. Time-Temperature-Desensitization diagram (TTDS diagram) for sensitized Type 304 stainless steels were developed by calculation assuming the chromium diffusion control for desensitization which might occur when the chromium depleted zone was healed up due to dissolution of chromium carbide and chromium diffusion from the matrix being heated at the solution annealing temperatures. TTDS diagrams calculated agree fairly well with ones determined by corrosion tests. Laser irradiation conditions (e.g., Laser power, beam diameter and traveling velocity) required for desensitization of sensitized Type 304 stainless steels were calculated using additivity rule from the TTDS diagram calculated and theoretical thermal curve of laser heating derived from the heat conduction theory. After laser beam irradiated under an optimum condition predicted by calculation, the sensitized HAZ of Type 304 stainless steel restored complete resistance to intergranular corrosion.

Emotional Desensitization to Violence Contributes to Adolescents’ Violent Behavior

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Mrug, Sylvie; Madan, Anjana; Windle, Michael

2015-01-01

Many adolescents are exposed to violence in their schools, communities and homes. Exposure to violence at high levels or across multiple contexts has been linked with emotional desensitization, indicated by low levels of internalizing symptoms. However, the long-term consequences of such desensitization are unknown. This study examined emotional desensitization to violence, together with externalizing problems, as mediators of the relationship between exposure to violence in pre-adolescence and violent behavior in late adolescence. A community sample of youth (N=704; 48% female; 76% African American, 22% Caucasian) reported on their exposure to violence in multiple settings at ages 11, 13 and 18. Internalizing and externalizing problems were assessed at ages 11 and 13; violent behavior was measured at age 18. Structural Equation Modeling showed that exposure to high levels of violence at age 11 was associated with lower levels of internalizing problems (quadratic effect) at age 13, as was exposure to violence across multiple contexts (linear effect). In turn, fewer internalizing problems and more externalizing problems at age 13 predicted more violent behavior at age 18. The results suggest that emotional desensitization to violence in early adolescence contributes to serious violence in late adolescence. PMID:25684447

Emotional Desensitization to Violence Contributes to Adolescents' Violent Behavior.

Science.gov (United States)

Mrug, Sylvie; Madan, Anjana; Windle, Michael

2016-01-01

Many adolescents are exposed to violence in their schools, communities and homes. Exposure to violence at high levels or across multiple contexts has been linked with emotional desensitization, indicated by low levels of internalizing symptoms. However, the long-term consequences of such desensitization are unknown. This study examined emotional desensitization to violence, together with externalizing problems, as mediators of the relationship between exposure to violence in pre-adolescence and violent behavior in late adolescence. A community sample of youth (N = 704; 48% female; 76% African American, 22% Caucasian) reported on their exposure to violence in multiple settings at ages 11, 13 and 18. Internalizing and externalizing problems were assessed at ages 11 and 13; violent behavior was measured at age 18. Structural Equation Modeling showed that exposure to high levels of violence at age 11 was associated with lower levels of internalizing problems (quadratic effect) at age 13, as was exposure to violence across multiple contexts (linear effect). In turn, fewer internalizing problems and more externalizing problems at age 13 predicted more violent behavior at age 18. The results suggest that emotional desensitization to violence in early adolescence contributes to serious violence in late adolescence.

Kidney transplantation after desensitization in sensitized patients: a Korean National Audit.

Science.gov (United States)

Huh, Kyu Ha; Kim, Beom Seok; Yang, Jaeseok; Ahn, Jeongmyung; Kim, Myung-Gyu; Park, Jae Berm; Kim, Jong Man; Chung, Byung-Ha; Kim, Joong Kyung; Kong, Jin Min

2012-10-01

The number of end-stage renal disease (ESRD) patients with preformed antibodies waiting for a kidney transplant has been increasing lately. We conducted a nationwide study on the outcomes of kidney transplantation after desensitization in Korea. Six transplant centers have run desensitization programs. The patients who underwent living donor kidney transplantation after desensitization from 2002 to 2010 were retrospectively analyzed. A total of 86 cases were enrolled. Thirty-five of these were cases of re-transplantation (40.7 %). Indications of desensitization were positive complement-dependent cytotoxicity (CDC) cross-match responses (CDC(+), 36.0 %), positive flow-cytometric cross-match responses (FCX(+), 54.7 %), and positive donor-specific antibodies (DSA(+), 8.1 %). The desensitization protocols used pre-transplant plasmapheresis (95.3 %), intravenous immunoglobulin (62.8 %), and rituximab (67.4 %). Acute rejection occurred in 18 patients (20.9 %), graft failure occurred in 4 patients, and the 3-year graft survival rate was 93.8 %. The presence of DSA increased the acute rejection rate (P = 0.015) and decreased the 1-year post-transplant estimated glomerular filtration rate (P = 0.006). Although rejection-free survival rates did not differ significantly between the CDC(+) and FCX(+) groups, the 1-year estimated glomerular filtration rate was lower in the CDC(+) group (P = 0.010). Infectious and significant bleeding complications occurred in 15.5 % and 4.7 % of cases, respectively. Kidney transplantation after desensitization had good graft outcomes and tolerable complications in Korea, and therefore, this therapy can be recommended for sensitized ESRD patients.

[Acetylsalicylic acid desensitization in the new era of percutaneous coronary intervention].

Science.gov (United States)

Fuertes Ferre, Georgina; Ferrer Gracia, Maria Cruz; Calvo Cebollero, Isabel

2015-09-21

Dual antiplatelet therapy is essential in patients undergoing percutaneous coronary intervention with stent implantation. Hypersensitivity to acetylsalicylic acid (ASA) limits treatment options. Desensitization to ASA has classically been studied in patients with respiratory tract disease. Over the last years, many protocols have been described about ASA desensitization in patients with ischemic heart disease, including acute coronary syndrome and the need for coronary stent implantation. It is important to know the efficacy and safety of ASA desensitization in these patients. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Desensitizing nano powders to electrostatic discharge ignition

International Nuclear Information System (INIS)

Steelman, Ryan; Daniels, Michael A.

2015-01-01

Electrostatic discharge (ESD) is a main cause for ignition in powder media ranging from grain silos to fireworks. Nanoscale particles are orders of magnitude more ESD ignition sensitive than their micron scale counterparts. This study shows that at least 13 vol. % carbon nanotubes (CNT) added to nano-aluminum and nano-copper oxide particles (nAl + CuO) eliminates ESD ignition sensitivity. The CNT act as a conduit for electric energy and directs electric charge through the powder to desensitize the reactive mixture to ignition. For nanoparticles, the required CNT concentration for desensitizing ESD ignition acts as a diluent to quench energy propagation.

Inhibitory effect of chitosan oligosaccharide on human hepatoma ...

African Journals Online (AJOL)

Background: Chitosan oligosaccharide, the degradation products of chitin, was reported to have a wide range of physiological functions and biological activities. In this study, we explored the inhibitory effect of Chitosan oligosaccharide on human hepatoma cells. Materials and Methods: MTT assay was applied to detect cell ...

Inhibition of calcineurin inhibits the desensitization of capsaicin evoked currents in cultured dorsal root ganglion neurones from adult rats

NARCIS (Netherlands)

Docherty, RJ; Yeats, JC; Bevan, S; Boddeke, HWGM

Capsaicin activates a non-specific cation conductance in mammalian sensory neurones. If capsaicin is applied continuously or repeatedly then there is a progressive decline in responsiveness. We have studied the mechanism of this desensitization using electrophysiological methods in cultured dorsal

A SAFE PROTOCOL FOR RAPID DESENSITIZATION IN PATIENTS WITH CYSTIC FIBROSIS AND ANTIBIOTIC HYPERSENSITIVITY

Science.gov (United States)

Legere, Henry J.; Palis, Ross I.; Bouza, Tito Rodriguez; Uluer, Ahmet Z.; Castells, Mariana C.

2009-01-01

Background CF patients often demonstrate hypersensitivity to one or multiple antibiotics due to frequent and repeated exposures. Attempts at antibiotic desensitization in this population are historically complicated by higher reaction rates, failure to complete the procedure and consequent withholding of first-line therapy. This study evaluates the outcomes of a rapid desensitization protocol developed at our institution. Methods We retrospectively reviewed the medical records of 15 patients undergoing 52 rapid antibiotic desensitizations at Brigham and Women’s Hospital and Children’s Hospital Boston utilizing our protocol. Results Mean FEV1 % predicted was 44.1 (SD 16.5), with two patients at desensitized during bilateral lung transplantation. Adverse reactions during desensitization occurred in 13.4%, and most were mild. 100% of patients completed the protocol and ultimately tolerated subsequent full-strength antibiotic courses. Conclusions CF patients with antibiotic hypersensitivity can safely receive first-line antibiotics via our rapid desensitization protocol, including those with severe obstructive lung disease. PMID:19740711

Hepatoma targeting peptide conjugated bio-reducible polymer complexed with oncolytic adenovirus for cancer gene therapy.

Science.gov (United States)

Choi, Joung-Woo; Kim, Hyun Ah; Nam, Kihoon; Na, Youjin; Yun, Chae-Ok; Kim, SungWan

2015-12-28

Despite adenovirus (Ad) vector's numerous advantages for cancer gene therapy, such as high ability of endosomal escape, efficient nuclear entry mechanism, and high transduction, and therapeutic efficacy, tumor specific targeting and antiviral immune response still remain as a critical challenge in clinical setting. To overcome these obstacles and achieve cancer-specific targeting, we constructed tumor targeting bioreducible polymer, an arginine grafted bio-reducible polymer (ABP)-PEG-HCBP1, by conjugating PEGylated ABP with HCBP1 peptides which has high affinity and selectivity towards hepatoma. The ABP-PEG-HCBP1-conjugated replication incompetent GFP-expressing ad, (Ad/GFP)-ABP-PEG-HCBP1, showed a hepatoma cancer specific uptake and transduction compared to either naked Ad/GFP or Ad/GFP-ABP. Competition assays demonstrated that Ad/GFP-ABP-PEG-HCBP1-mediated transduction was specifically inhibited by HCBP1 peptide rather than coxsackie and adenovirus receptor specific antibody. In addition, ABP-PEG-HCBP1 can protect biological activity of Ad against serum, and considerably reduced both innate and adaptive immune response against Ad. shMet-expressing oncolytic Ad (oAd; RdB/shMet) complexed with ABP-PEG-HCBP1 delivered oAd efficiently into hepatoma cancer cells. The oAd/ABP-PEG-HCBP1 demonstrated enhanced cancer cell killing efficacy in comparison to oAd/ABP complex. Furthermore, Huh7 and HT1080 cancer cells treated with oAd/shMet-ABP-PEG-HCBP1 complex had significantly decreased Met and VEGF expression in hepatoma cancer, but not in non-hepatoma cancer. In sum, these results suggest that HCBP1-conjugated bioreducible polymer could be used to deliver oncolytic Ad safely and efficiently to treat hepatoma. Copyright © 2015 Elsevier B.V. All rights reserved.

Self-Desensitization and Meditation in the Reduction of Public Speaking Anxiety.

Science.gov (United States)

Kirsch, Irving; Henry, David

1979-01-01

Speech-anxious students were assigned to self-administered treatment conditions: (1) systematic desensitization, (2) desensitization with meditation replacing progressive relaxation, and (3) meditation only. Treatment manuals included coping-skill instructions. Treatments were equally effective in reducing anxiety and produced a greater reduction…

[Prolonged desensitization pretreatment for in vitro fertilization in women with polycystic ovary].

Science.gov (United States)

Kuczyński, W; Czech, R; Redźko, S; Wasilewski, T; Mrugacz, G; Wołczyński, S; Pietrewicz, P; Grochowski, D; Szamatowicz, M

2000-09-01

To analyse the outcome of intracytoplasmic sperm injection (ICSI) in women with severe polycystic ovary disease (PCD), stimulated after prolonged pituitary desensitization in comparison with regular long protocol therapy. The results of controlled ovarian hyperstimulation (COH), fertilization rate, early embryo development parameters and clinical pregnancy rates were compared depending on the duration of pituitary desensitization before gonadotropin administration. A total of 60 patients with severe PCOD were desensitized with GnRH agonist up to 30 days before COH. The results were compared with the group of 213 patients with mild PCOD treated with regular long protocol (control). We observed a slightly higher rate of mature oocytes MII as well as the number of embryos obtained in the control group, however the pregnancy rate in the group with prolonged desensitization was significantly higher (50%) in comparison to the control group (33.8%). The prolonged pituitary desensitization before controlled ovarian hyperstimulation gives better chance for obtaining pregnancy in patients with severe PCOD. It could be recommended facing previous treatment failure.

Desensitization to ceftaroline in a patient with multiple medication hypersensitivity reactions.

Science.gov (United States)

Jones, Justin M; Richter, Lisa M; Alonto, Augusto; Leedahl, David D

2015-02-01

The case of a patient with multiple medication hypersensitivity reactions and a methicillin-resistant Staphylococcus aureus (MRSA) infection who underwent desensitization to ceftaroline is reported. A 32-year-old Caucasian woman with asthma, gastroesophageal reflux disease, heart murmur, and major depression was admitted for MRSA cellulitis with a subcutaneous abscess along the left sternomanubrial joint and clavicular osteomyelitis secondary to port placement after gastric bypass surgery. The patient had an extensive history of hypersensitivity reactions. Pertinent documented allergies were as follows: penicillin (anaphylaxis), daptomycin (anaphylaxis), vancomycin (hives), linezolid (hives), ertapenem (rash), ciprofloxacin (rash), and tigecycline (rash). The patient also reported previous reactions to aztreonam (unknown) and gentamicin (hives). The pharmacy was consulted to develop a desensitization protocol for ceftaroline. The desensitization protocol used three serial dilutions of ceftaroline to make 14 sequential infusions with escalating doses. Intramuscular epinephrine, i.v. diphenhydramine, and i.v. methylprednisolone were ordered as needed for the development of immediate hypersensitivity reactions during or after administration of ceftaroline. The cumulative dose (574.94 mg) was administered intravenously over 225 minutes with no breakthrough symptoms reported during or after the desensitization protocol. Ceftaroline fosamil 600 mg i.v. every 12 hours was continued for six weeks. Desensitization to ceftaroline was conducted for a patient with extensive history of hypersensitivity reactions to other drugs, including penicillin-induced anaphylaxis. Desensitization and subsequent treatment with full doses of ceftaroline were accomplished without apparent adverse effects. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.

Science.gov (United States)

Chen, Justin R; Buchmiller, Brett L; Khan, David A

2015-01-01

Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Percutaneous hepatic arterial catheterization for infusion chemotherapy in treatment of primary hepatoma

International Nuclear Information System (INIS)

Juhn, Jae Ryang; Chang, Jae Yong; Cha, Seong Sook; Han, Sang Suk; Bae, Cheol; Kim, Sung Rok; Chae, Yoo Soon

1984-01-01

Chemotherapy offers palliative treatment to patient with advanced nonresectable hepatoma. The usefulness of systemic chemotherapy is limited because of serious side reaction and low concentration of drug at tumor. But this problem may be overcome by intraarterial infusion. Nonsurgical percutaneous hepatic arterial catheterization was done in 21 patients with primary hepatoma, and infusion chemotherapy was done in 19 patients who were successful in catheterization. The results were as follows: 1. Selective catheterization of hepatic artery proper, common hepatic artery, and celiac artery were successful in 4, 9 and 4 patients respectively. The success rate of selective catheterization is 80.9% including celiac artery among 21 patients with hepatoma. 2. Simple catheterization method was applied in 14 patients, and catheter exchange and Loop methods were applied in 2 and 1 patient respectively. 3. Complication related to catheterization, such as infection and bleeding on punctured site, intimal injury and dislodgement of catheter were not serious. 4. Drugs were well tolerated without serious toxicity or complication. 5. 3 patients showed objective response and median survival time of treated patients is 2.5 months.

Desensitization strategies in adult heart transplantation-Will persistence pay off?

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Chih, Sharon; Patel, Jignesh

2016-08-01

Strategies are needed to enable successful heart transplantation in highly sensitized patients. Immunologic challenges from sensitization to human leukocyte antigen (HLA) reduce access to compatible donors, extend waiting times to transplant, and increase the risks of antibody-mediated rejection and cardiac allograft vasculopathy after transplant. The prime goal of desensitization is to increase access to transplantation through expansion of the donor organ pool. Existing therapies are directed at key components of the humoral immune response with newer biologically based regimens able to target plasma cells as the source of antibody production, as well as complement activation that has a central role in antibody-mediated injury. Despite the emergence of early promising results for these agents, a significant knowledge gap remains with the current data for desensitization, extrapolated mostly from non-heart solid-organ transplants and small observational studies. Notably, no approach has demonstrated significant and sustainable reductions in HLA antibody pre-transplant, and the ideal desensitization strategy remains elusive. In addition, clinical tools to evaluate the humoral response and efficacy of therapy are limited, focusing almost exclusively on HLA antibody detection. Importantly, desensitization is associated with significant costs and potential risks, and overall long-term outcomes and cost-effectiveness have not been sufficiently evaluated. Investigation is ongoing into the development of a clinically effective desensitization strategy in heart transplantation. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.

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Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

2016-02-01

Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±  16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.

Effectiveness of Structured Psychodrama and Systematic Desensitization in Reducing Test Anxiety.

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Kipper, David A.; Giladi, Daniel

1978-01-01

Students with examination anxiety took part in study of effectiveness of two kinds of treatment, structured psychodrama and systematic desensitization, in reducing test anxiety. Results showed that subjects in both treatment groups significantly reduced test-anxiety scores. Structured psychodrama is as effective as systematic desensitization in…

Cognitive Modification and Systematic Desensitization with Test Anxious High School Students.

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Leal, Lois L.; And Others

1981-01-01

Compares the relative effectiveness of cognitive modification and systematic desensitization with test anxious high school students (N=30). The systematic desensitization treatment appeared to be significantly more effective on the performance measure while cognitive modification was more effective on one of the self-report measures. (Author/JAC)

Studies on the Identification of Constituents in Ethanol Extract of Radix Glycyrrhizae and Their Anti-Primary Hepatoma Cell Susceptibility

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Jie Liu

2014-01-01

Full Text Available The objective of this paper is to study the chemical constituents of Radix Glycyrrhizae and to apply the resulting natural products in the study of drug susceptibility of hepatoma cells so as to provide a scientific basis for quality standards and clinical application of medicinal Radix Glycyrrhizae. Chromatographic materials were used for isolation and purification; structural identification was performed based on physicochemical properties and spectral data. MTT colorimetry was used to detect the proliferation inhibition rate against primary hepatoma cells by natural products, and flow cytometry was used to detect the changes in cell cycle progression. Five compounds were isolated and identified, namely, liquiritigenin (1, liquiritin (2, isoliquiritigenin (3, betulinic acid (4, and oleanolic acid (5. In the study, 5-FU (5-fluorouracil is used as a positive control to the hepatoma cells. Primary hepatoma cells were highly susceptible to 5-FU and liquiritigenin, both of which markedly inhibited the proliferation of hepatoma cells; flow cytometry results showed an increase in G0/G1 phase cells, a decrease in S phase cells, and a relative increase in G2/M phase cells. Primary hepatoma cells are highly susceptible to liquiritigenin, a natural product; the testing of tumor cell susceptibility is of important significance to the improvement of therapeutic effect of cancer.

Detrimental Effects of a Self-reward Contracting Program on Subjects' Involvement in Self-administered Desensitization

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Barrera, Manuel Jr.; Rosen, Gerald M.

1977-01-01

Assesses a self-reward contracting procedure intended to facilitate completion of self-administered desensitization. Self-referred snake phobics received either (a) self-administered desensitization; (b) self-administered desensitization with self-reward contracting; or (c) a self-administered placebo with self-reward contracting. Results show the…

Behavior Modification Through Covert Semantic Desensitization

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Hekmat, Hamid; Vanian, Daniel

1971-01-01

Results support the hypothesized relationship between meaning and phobia. Semantic desensitization techniques based on counter conditioning of meaning were significantly effective in altering the semantic value of the word from unpleasantness to neutrality. (Author)

Desensitization to inhaled aztreonam lysine in an allergic patient with cystic fibrosis using a novel approach.

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Guglani, Lokesh; Abdulhamid, Ibrahim; Ditouras, Joanna; Montejo, Jenny

2012-10-01

To report the successful desensitization of a highly allergic patient with cystic fibrosis (CF) to inhaled aztreonam lysine using the novel approach of intravenous desensitization followed by full-dose inhaled therapy without any adverse reactions. A 19-year-old woman with CF had persistent Pseudomonas aeruginosa-positive cultures and a history of type I hypersensitivity reactions to multiple medications, including aztreonam and tobramycin (intravenous and inhaled). To start therapy with an inhaled antipseudomonal antibiotic on a chronic basis, she underwent rapid desensitization to intravenous aztreonam followed by initiation of inhaled aztreonam lysine. Following intravenous desensitization with aztreonam, there was no adverse reaction or decline in lung function noted with inhaled aztreonam lysine and the chronic therapy was continued at home, with a modified regimen to maintain desensitization. Aztreonam lysine has been used for treatment of patients with CF with chronic P. aeruginosa colonization. Previous allergic reaction to intravenous aztreonam is considered a contraindication for use of aztreonam lysine. Our patient had a history of hives and facial swelling following administration of intravenous aztreonam (type I hypersensitivity reaction) as well as hypersensitivity to tobramycin. Rapid desensitization can be done for drugs that mediate a type I hypersensitivity reaction, with mast cells and basophils being the cellular targets. There are a few case reports of desensitization to inhaled antibiotics such as tobramycin and colistin, but desensitization to aztreonam lysine has not previously been reported. Desensitization of a patient with CF who is allergic to intravenous aztreonam was successfully accomplished with the novel approach of rapid intravenous desensitization followed by inhaled therapy. As inhaled antibiotics are being increasingly used for patients with CF, this novel strategy can be used for desensitizing allergic patients with CF to

Children's exposure to violent video games and desensitization to violence.

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Funk, Jeanne B

2005-07-01

Desensitization to violence is cited frequently as being an outcome of exposure to media violence and a condition that contributes to increased aggression. This article initiates the development of a conceptual model for describing possible relationships among violent video games, brain function, and desensitization by using empathy and attitudes toward violence as proxy measures of desensitization. More work is needed to understand how specific game content may affect brain activity, how brain development may be affected by heavy play at young ages, and how personality and lifestyle variables may moderate game influence. Given the current state of knowledge, recommendations are made for clinicians to help parents monitor and limit exposure to violent video games and encourage critical thinking about media violence.

Infectious complications in living-donor kidney transplant recipients undergoing multi-modal desensitization.

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Turza, Kristin C; Shafique, Michael; Lobo, Peter I; Sawyer, Robert G; Keith, Douglas S; Brayman, Kenneth L; Agarwal, Avinash

2014-06-01

Pre-existing humoral barriers challenge the transplantation of living donor kidneys (LDK) into highly sensitized ABO- and human leukocyte antigen (HLA)-incompatible recipients. Conditioning these LDK recipients' immune systems is required before they undergo transplantation. We hypothesized that medical desensitization would yield higher post-transplantation rates of infection. We conducted a study in which matched controls consisting of non-desensitized (NDS) LDK recipients were compared with desensitized (DS) receipients. Pre-transplantation desensitization included treatment with rituximab and mycophenolate mofetil followed by intravenous immunoglobulin (IVIg) and plasmapheresis. All participants in the study underwent induction therapy and maintenance immunosuppression. Primary outcomes included infection (opportunistic, local, systemic) within 12 mo after transplantation. Twenty-five patients underwent desensitization and LDK transplantation. Graft survival in the DS and NDS groups of patients was 96% and 98%, respectively. The mean 3- and 12-mo serum creatinine concentrations in the DS and NDS groups were 1.1±0.2 mg/dL and 1.2±0.3 mg/dL and 0.95±0.4 mg/dL and 0.73±0.8 mg/dL (p=0.3 and p=0.01), respectively. Thirty-six percent of the patients in the DS group had one or more infections, vs. 28% of those in the NDS group (p=0.1). No difference was observed in the frequency of opportunistic or systemic infections in the two groups. Local infections were statistically significantly more frequent in the DS group (60% vs. 30%, respectively; p=0.02). Pre-operative desensitization in highly sensitized LDK recipients is followed by a similar incidence of opportunistic and systemic infections as in NDS patients. Local infections were significantly more frequent in the DS than in the NDS patients in the study. With careful monitoring of infectious complications, pre-transplant desensitization permits LDK transplantation into highly sensitized patients.

Long-term effects of a single exposure to stress in adult rats on behavior and hypothalamic-pituitary-adrenal responsiveness: comparison of two outbred rat strains.

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Belda, Xavier; Márquez, Cristina; Armario, Antonio

2004-10-05

We have previously observed that a single exposure to immobilization (IMO), a severe stressor, caused long-term (days to weeks) desensitization of the response of the hypothalamic-pituitary-adrenal (HPA) axis to the homotypic stressor, with no changes in behavioral reactivity to novel environments. In contrast, other laboratories have reported that a single exposure to footshock induced a long-term sensitization of both HPA and behavioral responses to novel environments. To test whether these apparent discrepancies can be explained by the use of different stressors or different strains of rats, we studied in the present work the long-term effects of a single exposure to two different stressors (footshock or IMO) in two different strains of rats (Sprague-Dawley from Iffa-Credo and Wistar rats from Harlan). We found that both strains showed desensitization of the HPA response to the same (homotypic) stressor after a previous exposure to either shock or IMO. The long-term effects were higher after IMO than shock. No major changes in behavior in two novel environments (circular corridor, CC and elevated plus-maze, EPM) were observed after a single exposure to shock or IMO in neither strain, despite the fact that shocked rats showed a conditioned freezing response to the shock boxes. The present results demonstrate that long-term stress-induced desensitization of the HPA axis is a reliable phenomenon that can be observed with different stressors and strains. However, only behavioral changes related to shock-induced conditioned fear were found, which suggests that so far poorly characterized factors are determining the long-term behavioral consequences of a single exposure to stress.

Actions of exogenous histones and other proteins on [3H]-thymidine incorporation into DNA of Novikoff hepatoma cells

International Nuclear Information System (INIS)

Barra, R.; Beres, B.; Koch, M.R.; Lea, M.A.

1976-01-01

The effects of exogenous proteins on the incorporation of [ 3 H]-thymidine into DNA was studied in Novikoff hepatoma ascites cells incubated in Eagle's minimal essential medium. A liver cytosol fraction (8 mg protein/ml) caused approximately 80% inhibition of isotope incorporation. The inhibitory activity of cytosol fractions from Morris hepatomas 9618A 2 , 5123C and 20 were inversely related to their growth rate. Under conditions in which there appeared to be a density dependent inhibition of growth, a mean 10 to 20% stimulation of isotope incorporation was observed after addition of total calf thymus histones and individual fractions in the concentration range of 100 to 400μg/ml. In experiments with lower cell concentrations, a 60% or greater increase in [ 3 H]-thymidine incorporation could be obtained with total calf thymus histone and with Fl and arginine-rich histones from rat liver. At concentrations of 1 to 2 mg/ml, histones inhibited DNA synthesis. Bovine serum albumin had little effect on DNA synthesis. Polylysine caused an 80 to 90% inhibition at a concentration of 1 mg/ml, but stimulatory effects were detected under certain conditions at 10μg/ml. The results suggest critical dependence on the ratio of cell and exogenous protein concentration in the action of proteins on DNA synthesis. (author)

Desensitization: Overcoming the Immunologic Barriers to Transplantation

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Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.

2017-01-01

HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571

Desensitization of Children to Television Violence

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Cline, Victor B.; And Others

1973-01-01

To find if children do become desensitized to violence, a test for a measurable physiological difference in emotional response to filmed violence was administered to children who are high exposure and low exposure television viewers. (Author/KM)

Desensitization of Fire Bell Phobia

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O'Reilly, Patricia P.

1971-01-01

This case study presents an example of how one school psychologist helped a child and an entire class solve a problem. Although the techniques used are not unique to school psychological practice, the problems presented by their use are. The procedure consisted of a desensitization process lasting ten weeks. (Author)

Anorexia-cachexia syndrome in hepatoma tumour-bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC-1/GDF15.

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Borner, Tito; Arnold, Myrtha; Ruud, Johan; Breit, Samuel N; Langhans, Wolfgang; Lutz, Thomas A; Blomqvist, Anders; Riediger, Thomas

2017-06-01

The cancer-anorexia-cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators and tumour-derived factors are thought to play an important role in the aetiology of CACS. However, the central and peripheral mechanisms contributing to CACS are insufficiently understood. The area postrema (AP) and the nucleus tractus solitarii are two important brainstem centres for the control of eating during acute sickness conditions. Recently, the tumour-derived macrophage inhibitory cytokine-1 (MIC-1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC-1 in mice. Using a rat hepatoma tumour model, we examined the roles of the AP and of vagal afferents in the mediation of CACS. Specifically, we investigated whether a lesion of the AP (APX) or subdiaphragmatic vagal deafferentation (SDA) attenuate anorexia, body weight, muscle, and fat loss. Moreover, we analysed MIC-1 levels in this tumour model and their correlation with tumour size and the severity of the anorectic response. In tumour-bearing sham-operated animals mean daily food intake significantly decreased. The anorectic response was paralleled by a significant loss of body weight and muscle mass. APX rats were protected against anorexia, body weight loss, and muscle atrophy after tumour induction. In contrast, subdiaphragmatic vagal deafferentation did not attenuate cancer-induced anorexia or body weight loss. Tumour-bearing rats had substantially increased MIC-1 levels, which positively correlated with tumour size and cancer progression and negatively correlated with food intake. These findings demonstrate the importance of the AP in the mediation of cancer-dependent anorexia and body weight loss and support a pathological role of MIC-1 as a tumour-derived factor mediating CACS, possibly via an AP-dependent action. © 2016 The Authors. Journal of Cachexia, Sarcopenia and Muscle

[Experience of rapid drug desensitization therapy in the treatment of mycobacterial disease].

Science.gov (United States)

Sasaki, Yuka; Kurashima, Atsuyuki; Morimoto, Kozo; Okumura, Masao; Watanabe, Masato; Yoshiyama, Takashi; Ogata, Hideo; Gotoh, Hajime; Kudoh, Shoji; Suzuki, Hiroaki

2014-11-01

Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used. Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan. We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted. The underlying diseases were 7 cases of pulmonary Mycobacterium avium complex disease and 6 cases of pulmonary tuberculosis. Isoniazid was readministered in 2 (100%) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients. In Japan, the desensitization therapy recommended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

NDRG2 overexpression suppresses hepatoma cells survival during metabolic stress through disturbing the activation of fatty acid oxidation

International Nuclear Information System (INIS)

Pan, Tao; Zhang, Mei; Zhang, Fang; Yan, Guang; Ru, Yi; Wang, Qinhao; Zhang, Yao; Wei, Xuehui; Xu, Xinyuan; Shen, Lan; Zhang, Jian; Wu, Kaichun; Yao, Libo; Li, Xia

2017-01-01

Because of the high nutrient consumption and inadequate vascularization, solid tumor constantly undergoes metabolic stress during tumor development. Oncogenes and tumor suppressor genes participated in cancer cells' metabolic reprogramming. N-Myc downstream regulated gene 2 (NDRG2) is a recently identified tumor suppressor gene, but its function in cancer metabolism, particularly during metabolic stress, remains unclear. In this study, we found that NDRG2 overexpression significantly reduced hepatoma cell proliferation and enhanced cell apoptosis under glucose limitation. Moreover, NDRG2 overexpression aggravated energy imbalance and oxidative stress by decreasing the intracellular ATP and NADPH generation and increasing ROS levels. Strikingly, NDRG2 inhibited the activation of fatty acid oxidation (FAO), which preserves ATP and NADPH purveyance in the absence of glucose. Finally, mechanistic investigation showed that NDRG2 overexpression suppressed the glucose-deprivation induced AMPK/ACC pathway activation in hepatoma cells, whereas the expression of a constitutively active form of AMPK abrogated glucose-deprivation induced AMPK activation and cell apoptosis. Thus, as a negative regulator of AMPK, NDRG2 disturbs the induction of FAO genes by glucose limitation, leading to dysregulation of ATP and NADPH, and thus reduces the tolerance of hepatoma cells to glucose limitation. - Highlights: • NDRG2 overexpression reduces the tolerance of hepatoma cells to glucose limitation. • NDRG2 overexpression aggravates energy imbalance and oxidative stress under glucose deprivation. • NDRG2 overexpression disturbs the activation of FAO in hepatoma cells under glucose limitation. • NDRG2 overexpression inhibits the activation of AMPK/ACC pathway in hepatoma cells during glucose starvation.

Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK.

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Witting Christensen, S K; Kortekaas Krohn, I; Thuraiaiyah, J; Skjold, T; Schmid, J M; Hoffmann, H J H

2014-10-01

Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity. We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+) SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5-fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 min of allergen stimulation (n = 7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n = 10). Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, P desensitized with grass allergen. Challenge with grass allergen resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, P = 0.047) and correlated with decrease in CD63 upregulation (n = 7, r > 0.79, P Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An Aversion-Desensitization Treatment for Alcoholism

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Primo, Richard V.; And Others

1972-01-01

A six-to nine-month interview follow-up showed that five of the seven traceable Ss given the interpersonal aversion-systematic desensitization treatment had been abstinent, compared with only one of seven treated by the interpersonal aversion-control procedure. (Author)

Subthreshold Desensitization of Human Basophils Re-capitulates the Loss of syk and FcεRI expression Characterized by Other Methods of Desensitization

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MacGlashan, Donald

2012-01-01

Background Clinical desensitization of patients to drugs involves progressive exposure to escalating doses of drug over a period of 24 hours. In prior studies, this method was recapitulated in vitro to also demonstrate loss of mast cell or basophil responsiveness. However, most signaling studies of human basophils have identified changes in signaling by using other methods of inducing cellular desensitization. Objective This study examined two well-described endpoints of basophil desensitization, loss of syk or FcεRI expression, under conditions of subthreshold desensitization. Methods The loss of FceRI and syk was examined in human basophils. Results It was shown that both loss of syk and FcεRI/IgE occurred during an escalating series of stimulation (anti-IgE Ab) and that expression loss occurred despite the presence of little histamine release. If basophils were first cultured for 3 days in 10 ng/ml IL-3, the concentration-dependence of histamine release shifted to 100 fold lower concentrations of stimulus. However, loss of syk did not show any change in its EC50 while loss of FcεRI also shifted 100 fold. From the perspective of early signal element activation, the marked shift in the EC50 for histamine release was not accompanied by similar shifts in the EC50s for several signaling elements. The EC50s for phospho-Src, phospho-SHIP1, phospho-Syk, or phospho-Cbl did not change while the EC50s for phospho-Erk and the cytosolic calcium response did shift 100 fold. Conclusions These studies show that under normal conditions, subthreshold desensitization leads to loss of two critical signaling molecules (FcεRI and syk) but under at least one condition, treatment with IL-3, it is possible to markedly blunt the loss of syk, but not FcεRI, while executing a proper subthreshold titration. These data also suggest that IL-3 modifies only the sensitivity of signaling elements that are downstream of syk activation. PMID:22702505

Rate of Homologous Desensitization and Internalization of the GLP-1 Receptor.

Science.gov (United States)

Shaaban, Ghina; Oriowo, Mabayoje; Al-Sabah, Suleiman

2016-12-26

The glucagon-like peptide-1 receptor (GLP-1R) is an important target in the treatment of type 2 diabetes mellitus. The aim of this study was to compare the rate of agonist stimulated desensitization and internalization of GLP-1R. To this end, an N-terminally myc-tagged GLP-1R was stably expressed in HEK-293 cells. Homologous desensitization was assessed by measuring the cAMP response to agonist stimulation following pre-incubation with agonist for up to 120 min. Receptor internalization was monitored using an indirect ELISA-based method and confocal microscopy. Pre-incubation with GLP-1 resulted in a time-dependent loss of response to a second stimulation. Washing cells following pre-incubation failed to bring cAMP levels back to basal. Taking this into account, two desensitization rates were calculated: "apparent" (t 1/2 = 19.27 min) and "net" (t 1/2 = 2.99 min). Incubation of cells with GLP-1 also resulted in a time-dependent loss of receptor cell surface expression (t 1/2 = 2.05 min). Rapid agonist-stimulated internalization of GLP-1R was confirmed using confocal microscopy. Stimulation of GLP-1R with GLP-1 results in rapid desensitization and internalization of the receptor. Interestingly, the rate of "net" desensitization closely matches the rate of internalization. Our results suggest that agonist-bound GLP-1R continues to generate cAMP after it has been internalized.

The Role of Attention-Placebo Influences in the Efficacy of Systematic Desensitization

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McReynolds, William T.; And Others

1973-01-01

Systematic desensitization was compared with two attention-placebo control treatments--one taken from Paul and one currently devised as an elaborate, highly impressive therapeutic'' experience--and no treatment. It was hypothesized that (a) fear reductions following desensitization would be no greater than those associated with an equally…

Systematic Desensitization as a Method of Teaching a General Anxiety-Reducing Skill

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Zemore, Robert

1975-01-01

College students were treated with either a standard or modified version of systematic desensitization. Relative to a no-treatment control group, both treatment methods produced significant reductions in both the treated and untreated fears. The implications these findings have for two alternative conceptions of systematic desensitization are…

Radiation-induced segregation in desensitized type 304 austenitic stainless steel

International Nuclear Information System (INIS)

Ahmedabadi, Parag; Kain, V.; Arora, K.; Samajdar, I.; Sharma, S.C.; Bhagwat, P.

2011-01-01

Graphical abstract: Schematic representation of overall experimental and results, indicating attack, after the DL-EPR test, on grain boundaries, twin boundaries and pit-like features within grains at the depth of maximum attack. The sensitized specimen also showed severe attack on grain boundaries, however, attack on twin-boundaries and pit-like features were not noticed. Display Omitted Highlights: → Characterization of radiation-induced segregation done by EPR and AFM examination. → Cr depletion adjacent to carbides due to RIS in irradiated desensitized 304 SS. → Effectiveness as defect sink: twins > pit-like features > grain boundary. - Abstract: Radiation-induced segregation (RIS) in desensitized type 304 stainless steel (SS) was investigated using a combination of electrochemical potentiokinetic reactivation (EPR) test and atomic force microscopy (AFM). Desensitized type 304 SS was irradiated to 0.43 dpa (displacement per atom) using 4.8 MeV protons at 300 deg. C. The maximum attack in the EPR test for the irradiated desensitized SS was measured at a depth of 70 μm from the surface. Grain boundaries and twin boundaries got attacked and pit-like features within the grains were observed after the EPR test at the depth of 70 μm. The depth of attack, as measured by AFM, was higher at grain boundaries and pit-like features as compared to twin boundaries. It has been shown that the chromium depletion due to RIS takes place at the carbide-matrix as well as at the carbide-carbide interfaces at grain boundaries. The width of attack at grain boundaries after the EPR test of the irradiated desensitized specimen appeared larger due to the dislodgement of carbides at grain boundaries.

Radiation-induced segregation in desensitized type 304 austenitic stainless steel

Energy Technology Data Exchange (ETDEWEB)

Ahmedabadi, Parag, E-mail: adit@barc.gov.in [Materials Science Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Kain, V. [Materials Science Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Arora, K. [PEC University of Technology, Chandigarh (India); Samajdar, I. [Department of Metallurgical Engineering and Materials Science, Indian Institute Technology Bombay, Powai, Mumbai 400 076 (India); Sharma, S.C.; Bhagwat, P. [Nuclear Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

2011-09-30

Graphical abstract: Schematic representation of overall experimental and results, indicating attack, after the DL-EPR test, on grain boundaries, twin boundaries and pit-like features within grains at the depth of maximum attack. The sensitized specimen also showed severe attack on grain boundaries, however, attack on twin-boundaries and pit-like features were not noticed. Display Omitted Highlights: > Characterization of radiation-induced segregation done by EPR and AFM examination. > Cr depletion adjacent to carbides due to RIS in irradiated desensitized 304 SS. > Effectiveness as defect sink: twins > pit-like features > grain boundary. - Abstract: Radiation-induced segregation (RIS) in desensitized type 304 stainless steel (SS) was investigated using a combination of electrochemical potentiokinetic reactivation (EPR) test and atomic force microscopy (AFM). Desensitized type 304 SS was irradiated to 0.43 dpa (displacement per atom) using 4.8 MeV protons at 300 deg. C. The maximum attack in the EPR test for the irradiated desensitized SS was measured at a depth of 70 {mu}m from the surface. Grain boundaries and twin boundaries got attacked and pit-like features within the grains were observed after the EPR test at the depth of 70 {mu}m. The depth of attack, as measured by AFM, was higher at grain boundaries and pit-like features as compared to twin boundaries. It has been shown that the chromium depletion due to RIS takes place at the carbide-matrix as well as at the carbide-carbide interfaces at grain boundaries. The width of attack at grain boundaries after the EPR test of the irradiated desensitized specimen appeared larger due to the dislodgement of carbides at grain boundaries.

Oral desensitization to milk: how to choose the starting dose!

Science.gov (United States)

Mori, Francesca; Pucci, Neri; Rossi, Maria Elisabetta; de Martino, Maurizio; Azzari, Chiara; Novembre, Elio

2010-01-01

Mori F, Pucci N, Rossi ME, de Martino M, Azzari C, Novembre E. Oral desensitization to milk: how to choose the starting dose! Pediatr Allergy Immunol 2010: 21: e450–e453. © 2009 John Wiley & Sons A/S A renewed interest in oral desensitization as treatment for food allergy has been observed in the last few years. We studied a novel method based on the end point skin prick test procedure to establish the starting dose for oral desensitization in a group of 30 children higly allergic to milk. The results (in terms of reactions to the first dose administered) were compared with a group of 20 children allergic to milk as well. Such control group started to swallow the same dose of 0.015 mg/ml of milk. None reacted to the first dose when administered according to the end point skin prick test. On the other side, ten out of 20 children (50%) from the control group showed mild allergic reactions to the first dose of milk. In conclusion the end point skin prick test procedure results safe and easy to be performed in each single child in order to find out the starting dose for oral desensitization to milk, also by taking into account the individual variability. PMID:19624618

Effects of JS-K, a novel anti-cancer nitric oxide prodrug, on gene expression in human hepatoma Hep3B cells.

Science.gov (United States)

Dong, Ray; Wang, Xueqian; Wang, Huan; Liu, Zhengyun; Liu, Jie; Saavedra, Joseph E

2017-04-01

JS-K is a novel anticancer nitric oxide (NO) prodrug effective against a variety of cancer cells, including the inhibition of AM-1 hepatoma cell growth in rats. To further evaluate anticancer effects of JS-K, human hepatoma Hep3B cells were treated with JS-K and the compound control JS-43-126 at various concentrations (0-100μM) for 24h, and cytotoxicity was determined by the MTS assay. The compound control JS-43-126 was not cytotoxic to Hep3B cells at concentrations up to 100μM, while the LC 50 for JS-K was about 10μM. To examine the molecular mechanisms of antitumor effects of JS-K, Hep3B cells were treated with 1-10μM of JS-K for 24h, and then subjected to gene expression analysis via real time RT-PCR and protein immunostain via confocal images. JS-K is a GST-α targeting NO prodrug, and decreased immunostaining for GST-α was associated with JS-K treatment. JS-K activated apoptosis pathways in Hep3B cells, including induction of caspase-3, caspase-9, Bax, TNF-α, and IL-1β, and immunostaining for caspase-3 was intensified. The expressions of thrombospondin-1 (TSP-1) and the tissue inhibitors of metalloproteinase-1 (TIMP-1) were increased by JS-K at both transcript and protein levels. JS-K treatment also increased the expression of differentiation-related genes CD14 and CD11b, and depressed the expression of c-myc in Hep3B cells. Thus, multiple molecular events appear to be associated with anticancer effects of JS-K in human hepatoma Hep3B cells, including activation of genes related to apoptosis and induction of genes involved in antiangiogenesis and tumor cell migration. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cell death induced by Morarah and Khaltita in hepatoma cancer cells (Huh-7).

Science.gov (United States)

Baig, Saeeda; Alamgir, Mohiuddin

2009-10-01

To compare the combined and isolated growth inhibitory effects of Morarah and Khaltita (herbs) on hepatoma cell lines (Huh-7), through induction of apoptosis or necrosis. Comparative controlled in-vitro study. The Molecular Biology Laboratory, The Aga Khan University, Karachi, from June to December 2006. The growth of hepatoma cell lines (Huh-7) was checked by adding Khaltita and Morarah to the cells before culture in a 24 well plate. Six wells were selected and labeled for each of the four variables (controls, Khaltita, Morarah and mixture). After 2 days, cells were studied under an inverted phase contrast microscope and fields were recorded. Approximately four fields per slide of higher intensity were selected randomly to determine the dead cell density, and the procedure was repeated 10 or more times. Frequency and percentages were calculated for dead or alive cells in controls, Morarah, Khaltita and their mixture. Chi-square was used to compare the qualitative variables. P-values < 0.05 were considered significant. Morarah and Khaltita were found to induce statistically significant (p < 0.001) cell death in hepatoma cell lines (Huh-7). At a magnification of 40x, the controls showed 1% dead cells compared to 91% in Morarah, 83% in Khaltita and 73% in combined mixture of Khaltita and Morarah. At magnification of 20x, the controls showed 4% dead cells compared to 44% in Morarah, 47% in Khaltita and 49% in the combined mixture of Khaltita and Morarah. Morarah and Khaltita induced cell death in cultured hepatoma cells (Huh-7).

Desensitization of metastable intermolecular composites

Science.gov (United States)

Busse, James R [South Fork, CO; Dye, Robert C [Los Alamos, NM; Foley, Timothy J [Los Alamos, NM; Higa, Kelvin T [Ridgecrest, CA; Jorgensen, Betty S [Jemez Springs, NM; Sanders, Victor E [White Rock, NM; Son, Steven F [Los Alamos, NM

2011-04-26

A method to substantially desensitize a metastable intermolecular composite material to electrostatic discharge and friction comprising mixing the composite material with an organic diluent and removing enough organic diluent from the mixture to form a mixture with a substantially putty-like consistency, as well as a concomitant method of recovering the metastable intermolecular composite material.

Trichloroethylene toxicity in a human hepatoma cell line

Energy Technology Data Exchange (ETDEWEB)

Thevenin, E.; McMillian, J. [Medical Univ. of Charleston South Carolina, SC (United States)

1994-12-31

The experiments conducted in this study were designed to determine the usefullness of hepatocyte cultures and a human hepatoma cell line as model systems for assessing human susceptibility to hepatocellular carcinoma due to exposure to trichloroethylene. The results from these studies will then be analyzed to determine if human cell lines can be used to conduct future experiments of this nature.

Parental desensitization to violence and sex in movies.

Science.gov (United States)

Romer, Daniel; Jamieson, Patrick E; Bushman, Brad J; Bleakley, Amy; Wang, Anli; Langleben, Daniel; Jamieson, Kathleen Hall

2014-11-01

To assess desensitization in parents' repeated exposure to violence and sex in movies. A national US sample of 1000 parents living with at least 1 target child in 1 of 3 age groups (6 to 17 years old) viewed a random sequence of 3 pairs of short scenes with either violent or sexual content from popular movies that were unrestricted to youth audiences (rated PG-13 or unrated) or restricted to those under age 17 years without adult supervision (rated R). Parents indicated the minimum age they would consider appropriate to view each film. Predictors included order of presentation, parent and child characteristics, and parent movie viewing history. As exposure to successive clips progressed, parents supported younger ages of appropriate exposure, starting at age 16.9 years (95% confidence interval [CI], 16.8 to 17.0) for violence and age 17.2 years (95% CI, 17.0 to 17.4) for sex, and declining to age 13.9 years (95% CI, 13.7 to 14.1) for violence and 14.0 years (95% CI, 13.7 to 14.3) for sex. Parents also reported increasing willingness to allow their target child to view the movies as exposures progressed. Desensitization was observed across parent and child characteristics, violence toward both human and non-human victims, and movie rating. Those who frequently watched movies were more readily desensitized to violence. Parents become desensitized to both violence and sex in movies, which may contribute to the increasing acceptance of both types of content by both parents and the raters employed by the film industry. Copyright © 2014 by the American Academy of Pediatrics.

Clinical practice - Drug desensitization in children

NARCIS (Netherlands)

de Groot, H.; Mulder, W.M.C.

2010-01-01

Immediate type allergic reactions to medication are potentially life threatening and can hamper drug therapy of several medical conditions. Exact incidence and prevalence data for these reactions in children are lacking. If no alternative drug treatment is available, a desensitization procedure may

Perioperative Desensitization Improves Outcomes Among Crossmatch Positive Recipients of Deceased Donor Renal Transplants.

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Sharma, Amit; King, Anne; Kumar, Dhiren; Behnke, Martha; McDougan, Felecia; Kimball, Pamela M

2016-06-01

Graft failure due to chronic rejection is greater among renal transplant patients with donor-specific antibody (DSA) than among DSA-free patients. For patients dependent on deceased donor transplantation, preoperative desensitization to eliminate DSAs may be impractical. We speculated that perioperative desensitization might eliminate preexisting DSAs and prevent de novo DSAs and improve graft outcomes. We report that brief perioperative desensitization using either intravenous immunoglobulin (IVIG) or plasmapheresis/IVIG (PP/IVIG) treatment improves clinical outcomes among patients with positive crossmatches. Immediately following deceased donor transplantation, 235 renal recipients were assigned points for PRA and flow crossmatches (FCXM): delayed graft function (DGF) ≤ 1 point received standard therapy; 2 points received high-dose IVIG; and ≥3 points received PP/IVIG. The DSAs were serially monitored by single antigen bead luminex for 1 year. Five-year clinical outcomes were determined from the chart review. All desensitized patients had preoperatively positive FCXM with DSA. Rejection was more common (P desensitized than nonsensitized groups. However, overall graft survivals were similar between the groups (P = not significant) and superior to historic untreated patients (P 90% in all desensitizated patients with DSA elimination as well as PP/IVIG patients with residual DSA. In contrast, IVIG patients with persistent DSA had poorer graft survival (45%, P desensitization improved overall graft survival of sensitized patients compared to historic untreated patients. Plasmapheresis/IVIG had greater impact on DSA eradication and graft survival than IVIG alone. © 2016, NATCO.

the use of systematic desensitization in psychotherapy

African Journals Online (AJOL)

relaxation inhibits anxiety-their concurrent expression is physiologically impossible. ..... fifth-floor balcony without discomfort. Four months after her return ... specific rather than 'free-floating' anxiety is present, systematic ,. 6. desensitization is ...

Lymphocyte-mediated regulation of platelet activation during desensitization in patients with hymenoptera venom hypersensitivity.

Science.gov (United States)

Ledru, E; Pestel, J; Tsicopoulos, A; Joseph, M; Wallaert, B; Tonnel, A B; Capron, A

1988-01-01

T cells from peripheral blood of hymenoptera sensitive patients were studied before and after venom desensitization. Before treatment, T cells showed a variable but higher proliferative response to allergen than T cells of treated patients or controls. While before desensitization, T cell products, specifically released after in vitro allergen stimulation, were able to amplify the IgE-dependent platelet activity, we showed that after treatment of the same patients, T cell products strongly reduced platelet activation. Considering the modifications in platelet activation previously observed in patients treated by specific immunotherapy, the present results suggest that, through a modification of T cell reactivity to allergen, T cell functions are modulated by desensitization, and emphasize the involvement of T cell products in the desensitization mechanisms. PMID:3263227

Dosimetric considerations in radioimmunotherapy of patients with hepatoma

International Nuclear Information System (INIS)

Leichner, P.K.; Klein, J.L.; Order, S.E.

1986-01-01

Dosimetric studies of I-131 labeled antiferritin have provided the foundation for preparative and administrative aspects of radiolabeled antibody treatment of patients with hepatoma. Tumor response to I-131 labeled antiferritin IgG was encouraging and radioimmunotherapy with Y-90 labeled antiferritin IgG was recently initiated. For these patients, In-111 labeled antiferritin IgG was used as the imaging agent, with administered activities ranging from 0.8 - 7 mCi. Serial gamma camera imaging from 30 minutes to 6 days post injection demonstrated that 5-30% of the administered activity localized in hepatomas (8/12 patients). The mean value of the effective half-life in the tumor and liver was 2.8 d. Disappearance curves for the blood circulation, spleen, and other normal tissues were biphasic such that 50% of the activity disappeared within 24 hours post injection. The eight patients who demonstrated sufficient tumor localization where subsequently treated with Y-90 labeled antiferritin IgG. Administered activities were dependent on tumor volume and uptake of radiolabeled IgG and ranged from 8 - 20 mCi. The remaining patients were treated under other existing protocols. 10 references

Endemic Images and the Desensitization Process.

Science.gov (United States)

Saigh, Philip A.; Antoun, Fouad T.

1984-01-01

Examined the effects of endemic images on levels of anxiety and achievement of 48 high school students. Results suggested that a combination of endemic images and study skills training was as effective as desensitization plus study skills training. Includes the endemic image questionnaire. (JAC)

Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century.

Science.gov (United States)

Castells Guitart, M C

2014-01-01

The frequency of hypersensitivity reactions (HSR) to drugs has risen in the last 10 years owing to increased exposure to better and more allergenic medications including monoclonal antibodies. HSRs prevent patients from using their first-line therapy, leading to decreased quality of life and life expectancy. Although premedication with antihistamines, leukotriene blockers, and corticosteroids can protect against mild-to-moderate HSR, none of these medications has provided protection against anaphylaxis. Rapid drug desensitization is a treatment option for patients with HSR to their first-line medication that protects against anaphylaxis.Although the mechanisms of drug desensitization are not completely understood, in vitro mast cell models of IgE antigen desensitization have led to the design of safe and effective in vivo protocols aimed at protecting highly sensitized patients from hypersensitivity reactions and anaphylaxis. This review provides an insight into the mechanisms of IgE/mast cell desensitization, the principles and practice of drug desensitization, and an overview of the different desensitization protocols and their safety and efficacy profiles. Drug desensitization should only be performed by allergists, trained nurses, and experienced pharmacists, since this high-risk procedure involves reintroducing allergenic medication to highly sensitized patients, with the consequent potential for severe or fatal HSRs.

Acute activation, desensitization and smoldering activation of human acetylcholine receptors.

Directory of Open Access Journals (Sweden)

Barbara G Campling

Full Text Available The behavioral effects of nicotine and other nicotinic agonists are mediated by AChRs in the brain. The relative contribution of acute activation versus chronic desensitization of AChRs is unknown. Sustained "smoldering activation" occurs over a range of agonist concentrations at which activated and desensitized AChRs are present in equilibrium. We used a fluorescent dye sensitive to changes in membrane potential to examine the effects of acute activation and chronic desensitization by nicotinic AChR agonists on cell lines expressing human α4β2, α3β4 and α7 AChRs. We examined the effects of acute and prolonged application of nicotine and the partial agonists varenicline, cytisine and sazetidine-A on these AChRs. The range of concentrations over which nicotine causes smoldering activation of α4β2 AChRs was centered at 0.13 µM, a level found in smokers. However, nicotine produced smoldering activation of α3β4 and α7 AChRs at concentrations well above levels found in smokers. The α4β2 expressing cell line contains a mixture of two stoichiometries, namely (α4β22β2 and (α4β22α4. The (α4β22β2 stoichiometry is more sensitive to activation by nicotine. Sazetidine-A activates and desensitizes only this stoichiometry. Varenicline, cytisine and sazetidine-A were partial agonists on this mixture of α4β2 AChRs, but full agonists on α3β4 and α7 AChRs. It has been reported that cytisine and varenicline are most efficacious on the (α4β22α4 stoichiometry. In this study, we distinguish the dual effects of activation and desensitization of AChRs by these nicotinic agonists and define the range of concentrations over which smoldering activation can be sustained.

Cow's Milk Desensitization in Anaphylactic Patients: A New Personalized-dose Method.

Science.gov (United States)

Babaie, Delara; Nabavi, Mohammad; Arshi, Saba; Mesdaghi, Mehrnaz; Chavoshzadeh, Zahra; Bemanian, Mohammad Hasan; Tafakori, Mitra; Amirmoini, Mehrdad; Esmailzadeh, Hosein; Molatefi, Rasoul; Rekabi, Mahsa; Akbarpour, Nadieh; Masoumi, Farimah; Fallahpour, Morteza

2017-02-01

Cow's milk allergy (CMA) is the most frequent food allergy in children and oral immunotherapy (OIT) is a promising approach for treatment of patients. The most challenging cases are anaphylactic with coexisting asthma and proposing safe protocols is crucial especially in high risk groups. Considering that CMA varies among patients, an individualized OIT protocol would be beneficial to achieve a safer and more efficient method of desensitization. 18 children more than 3 years of age with IgE-mediated CMA were enrolled. CMA was confirmed by positive skin prick test (SPT) and positive oral food challenge (OFC) and 60% of individuals had a convincing history of persistent asthma. SPT with milk extracts, whole fresh milk and serially diluted milk concentrations were performed.  The dilution of milk that induced 3-5 mm of wheal in each individual was selected as the starting dilution for OIT. Desensitization began by 1 drop of the defined dilution and continued increasingly. Overall, 16 out of 18 children (88.8%) achieved the daily intake of 120 mL of milk. Four out of these 16 children accomplished the protocol without any adverse allergic reactions. 12 patients experienced mild to severe reactions. Wheal and erythema in SPT (p≤0.001), and sIgE (p≤0.003) to most milk allergens were significantly decreased following desensitization. We successfully desensitized 16 of 18 children with IgE-mediated CMA by individualized desensitization protocol. Individualizing the OIT protocol would be helpful to save time and perhaps to relieve the allergic symptoms after ingesting cow's milk intake.

Effects of Two Short-Term Desensitization Methods in the Treatment of Test Anxiety

Science.gov (United States)

Richardson, Frank C.; Suinn, Richard M.

1974-01-01

Accelerated massed desensitization and anxiety management training were compared with standard systematic desensitization in terms of reducing self-reported test anxiety in high test-anxious college students. All three treatments significantly reduced test anxiety as compared with a waiting list control group. (Author)

Group Systematic Desensitization Versus Covert Positive Reinforcement in the Reduction of Test Anxiety

Science.gov (United States)

Kostka, Marion P.; Galassi, John P.

1974-01-01

The study compared modified versions of systematic desensitization and covert positive reinforcement to a no-treatment control condition in the reduction of test anxiety. On an anagrams performance test, the covert reinforcement and control groups were superior to the desensitization group. (Author)

Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment.

Science.gov (United States)

Madrigal-Burgaleta, R; Berges-Gimeno, M P; Angel-Pereira, D; Ferreiro-Monteagudo, R; Guillen-Ponce, C; Pueyo, C; Gomez de Salazar, E; Alvarez-Cuesta, E

2013-07-01

Desensitization to antineoplastic agents is becoming a standard of care. Efforts to establish and improve these techniques are being made at many institutions. Our aims are to evaluate a new rapid desensitization protocol designed to be shorter (approximately 4 h) and safer (reducing hazardous drugs exposure risks) and to assess the oxaliplatin-specific immunoglobulin E (IgE) as a novel diagnostic tool. Prospective, observational, longitudinal study with patients who, for a 1-year period, suffered reactions to antineoplastic agents and were referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were included or excluded as desensitization candidates after anamnesis, skin testing, risk assessment, and graded challenge. Specific IgE was determined in oxaliplatin-reactive patients. Candidate patients were desensitized using the new RCUH rapid desensitization protocol. Of 189 intravenous rapid desensitizations, 188 were successfully accomplished in the 23 patients who met inclusion criteria for desensitization (of 58 referred patients). No breakthrough reactions occurred in 94% of desensitizations, and most breakthrough reactions were mild. In 10 oxaliplatin-reactive patients, 38 desensitizations were successfully accomplished. Sensitivity for oxaliplatin-specific IgE was 38% (0.35UI/l cutoff point) and 54% (0.10UI/l cutoff point); specificity was 100% for both cutoff points. In the hands of a Desensitization Program, managed by drug desensitization experts, this new protocol has proven an effective therapeutic tool for hypersensitivity to several antineoplastic agents (oxaliplatin, carboplatin, paclitaxel, docetaxel, cyclophosphamide, and rituximab); moreover, it improves safety handling of hazardous drugs. We report the first large series of oxaliplatin desensitizations. Oxaliplatin-specific IgE determination could be helpful. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The desensitization gating of the MthK K+ channel is governed by its cytoplasmic amino terminus.

Directory of Open Access Journals (Sweden)

Mario Meng-Chiang Kuo

2008-10-01

Full Text Available The RCK-containing MthK channel undergoes two inactivation processes: activation-coupled desensitization and acid-induced inactivation. The acid inactivation is mediated by the C-terminal RCK domain assembly. Here, we report that the desensitization gating is governed by a desensitization domain (DD of the cytoplasmic N-terminal 17 residues. Deletion of DD completely removes the desensitization, and the process can be fully restored by a synthetic DD peptide added in trans. Mutagenesis analyses reveal a sequence-specific determinant for desensitization within the initial hydrophobic segment of DD. Proton nuclear magnetic resonance ((1H NMR spectroscopy analyses with synthetic peptides and isolated RCK show interactions between the two terminal domains. Additionally, we show that deletion of DD does not affect the acid-induced inactivation, indicating that the two inactivation processes are mutually independent. Our results demonstrate that the short N-terminal DD of MthK functions as a complete moveable module responsible for the desensitization. Its interaction with the C-terminal RCK domain may play a role in the gating process.

Receptor downregulation and desensitization enhance the information processing ability of signalling receptors

Directory of Open Access Journals (Sweden)

Resat Haluk

2007-11-01

Full Text Available Abstract Background In addition to initiating signaling events, the activation of cell surface receptors also triggers regulatory processes that restrict the duration of signaling. Acute attenuation of signaling can be accomplished either via ligand-induced internalization of receptors (endocytic downregulation or via ligand-induced receptor desensitization. These phenomena have traditionally been viewed in the context of adaptation wherein the receptor system enters a refractory state in the presence of sustained ligand stimuli and thereby prevents the cell from over-responding to the ligand. Here we use the epidermal growth factor receptor (EGFR and G-protein coupled receptors (GPCR as model systems to respectively examine the effects of downregulation and desensitization on the ability of signaling receptors to decode time-varying ligand stimuli. Results Using a mathematical model, we show that downregulation and desensitization mechanisms can lead to tight and efficient input-output coupling thereby ensuring synchronous processing of ligand inputs. Frequency response analysis indicates that upstream elements of the EGFR and GPCR networks behave like low-pass filters with the system being able to faithfully transduce inputs below a critical frequency. Receptor downregulation and desensitization increase the filter bandwidth thereby enabling the receptor systems to decode inputs in a wider frequency range. Further, system-theoretic analysis reveals that the receptor systems are analogous to classical mechanical over-damped systems. This analogy enables us to metaphorically describe downregulation and desensitization as phenomena that make the systems more resilient in responding to ligand perturbations thereby improving the stability of the system resting state. Conclusion Our findings suggest that in addition to serving as mechanisms for adaptation, receptor downregulation and desensitization can play a critical role in temporal information

Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates.

Science.gov (United States)

Yabu, Julie M; Siebert, Janet C; Maecker, Holden T

2016-01-01

Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize

Anaphylactic reaction to polyethylene-glycol conjugated-asparaginase: premedication and desensitization may not be sufficient.

Science.gov (United States)

Sahiner, Umit M; Yavuz, S Tolga; Gökce, Muge; Buyuktiryaki, Betul; Altan, Ilhan; Aytac, Selin; Tuncer, Murat; Tuncer, Ayfer; Sackesen, Cansin

2013-08-01

In hypersensitive reactions to native L-asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG-ASP) is preferred. Anaphylaxis with PEG-ASP is rare. An 8-year-old girl and a 2.5-year-old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L-asparaginase hypersensitivity and substitution with PEG-ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG-ASP infusion. Both patients developed anaphylaxis with peg-asparaginase. These are the first reported cases of anaphylactic reaction to PEG-ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG-ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

Comparison of Anxiety Management Training and Desensitization in Reducing Test and Other Anxieties.

Science.gov (United States)

Deffenbacher, Jerry L.; Shelton, John L.

1978-01-01

Effects of systematic desensitization and anxiety management training in reducing test anxiety and generalizing to other anxieties were compared. Both desensitization and anxiety management training produced significant reduction of text anxiety, but by follow-up, anxiety management training produced significantly more test-anxiety reduction on…

Antioxidative and apoptotic properties of polyphenolic extracts from edible part of artichoke (Cynara scolymus L.) on cultured rat hepatocytes and on human hepatoma cells.

Science.gov (United States)

Miccadei, Stefania; Di Venere, Donato; Cardinali, Angela; Romano, Ferdinando; Durazzo, Alessandra; Foddai, Maria Stella; Fraioli, Rocco; Mobarhan, Sohrab; Maiani, Giuseppe

2008-01-01

Cultured rat hepatocytes and human hepatoma HepG2 cells were used to evaluate the hepatoprotective properties of polyphenolic extracts from the edible part of artichoke (AE). The hepatocytes were exposed to H2O2generated in situ by glucose oxidase and were treated with either AE, or pure chlorogenic acid (ChA) or with the well known antioxidant, N, N'-diphenyl-p-phenilenediamine (DPPD). Addition of glucose oxidase to the culture medium caused depletion of intracellular glutathione (GSH) content, accumulation of malondialdehyde (MDA) in the cultures, as a lipid peroxidation indicator, and cell death. These results demonstrated that AE protected cells from the oxidative stress caused by glucose oxidase, comparable to DPPD. Furthermore, AE, as well as ChA, prevented the loss of total GSH and the accumulation of MDA. Treatment of HepG2 cells for 24 h with AE reduced cell viability in a dose-dependent manner, however, ChA had no prominent effects on the cell death rate. Similarly, AE rather than ChA induced apoptosis, measured by flow cytometric analysis of annexin and by activation of caspase-3, in HepG2 cells. Our findings indicate that AE had a marked antioxidative potential that protects hepatocytes from an oxidative stress. Furthermore, AE reduced cell viability and had an apoptotic activity on a human liver cancer cell line.

Extensive FDG uptake and its modification with corticosteroid in a granuloma rat model: an experimental study for differentiating granuloma from tumors

International Nuclear Information System (INIS)

Zhao, Songji; Takei, Toshiki; Zhao, Yan; Tamaki, Nagara; Kuge, Yuji; Kohanawa, Masashi; Takahashi, Toshiyuki; Kawashima, Hidekazu; Temma, Takashi; Seki, Koh-ichi

2007-01-01

Increased 18 F-fluorodeoxyglucose (FDG) uptake in inflammatory lesions, particularly in granulomatous inflammation (e.g., sarcoidosis), makes it difficult to differentiate malignant tumors from benign lesions and is the main source of false-positive FDG-PET findings in oncology. Here, we developed a rat granuloma model and examined FDG uptake in the granuloma. The effects of corticosteroid on FDG uptake in the granuloma were compared with those in a malignant tumor. Rats were inoculated with Mycobacterium bovis bacillus Calmette-Guerin (BCG) or allogenic hepatoma cells, and subdivided into control and pretreated (methylprednisolone acetate, 8 mg/kg i.m.) groups. Radioactivity in tissues was determined 1 h after the FDG injection. FDG-PET was performed in rats bearing BCG granulomas or tumors before and after prednisolone treatment. Mature epithelioid cell granuloma-formation and massive lymphocyte-infiltration were observed in the control group of granuloma, histologically similar to sarcoidosis. The mean FDG uptake in the granuloma was comparable to that in the hepatoma. Prednisolone reduced epithelioid cell granuloma-formation and lymphocyte-infiltration. Prednisolone significantly decreased the level of FDG uptake in the granuloma (52% of control), but not in the hepatoma. The FDG uptake levels in the granulomas and tumors were clearly imaged with PET. We developed an intramuscular granuloma rat model that showed a high FDG uptake comparable to that of the tumor. The effect of prednisolone pretreatment on FDG uptake was greater in the granuloma than in the tumor. These results suggest that BCG-induced granuloma may be a valuable model and may provide a biological basis for FDG studies. (orig.)

Flooding and Systematic Desensitization: Efficacy in Subclinical Phobics as a Function of Arousal

Science.gov (United States)

Suarez, Yolanda; And Others

1976-01-01

Flooding and systematic desensitization procedures were investigated for possible interactions with subject arousal level on reduction in phobic reactions. No such interaction was found. Behaviorally and on GSR response, both flooding and systematic desensitization were effective, but only the latter was effective on subjective reports. (NG)

Total Saponin from Root of Actinidia valvata Dunn Inhibits Hepatoma 22 Growth and Metastasis In Vivo by Suppression Angiogenesis

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Guo-Yin Zheng

2012-01-01

Full Text Available The root of Actinidia valvata dunn has been widely used in the treatment of hepatocellular carcinoma (HCC, proved to be beneficial for a longer and better life in China. In present work, total saponin from root of Actinidia valvata Dunn (TSAVD was extracted, and its effects on hepatoma H22-based mouse in vivo were observed. Primarily transplanted hypodermal hepatoma H22-based mice were used to observe TSAVD effect on tumor growth. The microvessel density (MVD, vascular endothelial growth factor (VEGF, basic fibroblast growth factor (bFGF are characterized factors of angiogenesis, which were compared between TSAVD-treated and control groups. Antimetastasis effect on experimental pulmonary metastasis hepatoma mice was also observed in the study. The results demonstrated that TSAVD can effectively inhibit HCC growth and metastasis in vivo, inhibit the formation of microvessel, downregulate expressions of VEGF and bFGF, and retrain angiogenesis of hepatoma 22 which could be one of the reasons.

Anti-hepatoma activity of a novel compound glaucocalyxin H in vivo and in vitro.

Science.gov (United States)

Hai, Guangfan; Zhang, Chong; Jia, Yanlong; Bai, Suping; Han, Jinfen; Guo, Lanqing; Cui, Taizhen; Niu, Bingxuan; Huang, Feng; Song, Yu

2015-06-01

Glaucocalyxin H (GLH) is a new compound isolated from a traditional Chinese medical herb Isodon japonica var. glaucocalyx which has been used for folk medicine. This study was carried out for the first time to investigate the potential role of GLH in anti-hepatoma activity and underlying mechanisms in it. GLH could inhibit the growth of tumor in mice and induce HepG2 cells to death as assessed by the tumor reduction assay, toxic assay, morphological change, and survival rate assay. Many antitumor drugs originated from plants could inhibit the growth of tumor by inducing cells to apoptosis. The morphological changes of HepG2 cells treated with different concentrations of GLH under fluorescence and electron microscope and apoptotic rates were detected to verify its effect on apoptosis. As shown in the study, GLH could induce HepG2 cells to apoptosis in a dose-dependent manner. Bcl2 and Bax proteins played important roles in apoptosis and the disequilibrium between Bcl2 and Bax might result in apoptosis. The expression of Bax protein was upregulated and Bcl2 protein was downregulated in HepG2 cells treated with GLH assessed by Western blotting, and they were in a dose-dependent manner. Taken together, GLH can inhibit the growth of hepatoma cells in vivo and in vitro by inducing cell apoptosis due to the decreased Bcl2 and increased Bax proteins suggesting that GLH could be a potential candidate as an anti-hepatoma agent for the therapeutic treatment of hepatoma.

Hyperventilation in a motion sickness desensitization program

NARCIS (Netherlands)

Mert, A.; Bles, W.; Nooij, S.A.E.

2007-01-01

Introduction: In motion sickness desensitization programs, the motion sickness provocative stimulus is often a forward bending of the trunk on a rotating chair, inducing Coriolis effects. Since respiratory relaxation techniques are applied successfully in these courses, we investigated whether these

Role Of Expectancy Manipulation In Systematic Desensitization

Science.gov (United States)

Brown, H. Alan

1973-01-01

Expectancy, relaxation, and hierarchy content were manipulated. Findings did not support the hypothesis that expectancy was the only factor in desensitization, but did clarify the role of expectancy vis-a-vis the counterconditioning elements typically discussed in the literature. (Author)

Effect of interleukin-17A on stemness of hepatoma cell lines

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LI Kexin

2017-06-01

Full Text Available ObjectiveTo investigate the effect of interleukin-17A (IL-17A on stemness of human hepatoma cell lines Hep 3B, MHCC97H, and MHCC97L and the association between IL-17A and the progression of liver cancer. MethodsHuman hepatoma cell lines Hep 3B, MHCC97H, and MHCC97L were selected, and in vitro 3D sphere formation assay was used to analyze the effect of IL-17A on sphere formation ability. The control group with common culture solution and the experimental group with 50 ng/ml IL-17A were established. Real-time cellular analysis was used to determine the effect of IL-17A on the proliferation and migration of hepatoma cells with enhanced sphere formation ability; quantitative real-time PCR was used to measure the changes in the mRNA expression of IL-17A receptors IL-17RA and IL-17RC and stemness-related genes SOX2, NANOG, OCT4, and BMI1 in hepatoma cells with enhanced sphere formation ability; Western blot was used to measure the expression of epithelial-mesenchymal transition-related proteins E-cadherin, N-cadherin, and vimentin. The t-test was used for comparison of continuous doota betwwen groups. ResultsWith the presence of 50 ng/ml IL-17A and 500 inoculated cells, Hep 3B cells had a significant increase in the number of spheres formed (113.0±10.3 vs 180.0±7.2, t=5.533, P＜0.001, while MHCC97H and MHCC97L cells showed no significant changes (t=1.087 and 0.279, P=0.325 and 0785. The analysis showed that IL-17A promoted the proliferation and migration of Hep 3B cells with an increased number of spheres formed. After the addition of 50 ng/ml IL-17A, there was an increase in the mRNA expression of IL-17A receptors IL-17RA and IL-17RC over the time of treatment; Hep 3B cells showed significant increases in the mRNA expression of stemness-related genes SOX2 (t=4.749, P=0.042, NANOG (t=19.600, P=0.003, OCT4 (t=37.310, P＜0.001, and BMI1 (t=16.810, P=0.004. Western blot showed no significant change in the expression of the epithelium

Agonist-induced desensitization of human β3-adrenoceptors expressed in human embryonic kidney cells

NARCIS (Netherlands)

Michel-Reher, Martina B.; Michel, Martin C.

2013-01-01

β3-Adrenoceptors are resistant to agonist-induced desensitization in some cell types but susceptible in others including transfected human embryonic kidney (HEK) cells. Therefore, we have studied cellular and molecular changes involved in agonist-induced β3-adrenoceptor desensitization in HEK cells.

Opioid receptor desensitization: mechanisms and its link to tolerance

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Stéphane eAllouche

2014-12-01

Full Text Available Opioid receptors are part of the class A of G-protein coupled receptors and the target of the opiates, the most powerful analgesic molecules used in clinic. During a protracted use, a tolerance to analgesic effect develops resulting in a reduction of the effectiveness. So understanding mechanisms of tolerance is a great challenge and may help to find new strategies to tackle this side effect. This review will summarize receptor-related mechanisms that could underlie tolerance especially receptor desensitization. We will focus on the latest data obtained on molecular mechanisms involved in opioid receptor desensitization: phosphorylation, receptor uncoupling, internalization and post-endocytic fate of the receptor.

Effect of aspirin desensitization on T-cell cytokines and plasma lipoxins in aspirin-exacerbated respiratory disease.

Science.gov (United States)

Aksu, Kurtuluş; Kurt, Emel; Alatas, Özkan; Gülbas, Zafer

2014-01-01

The pathogenesis of aspirin-exacerbated respiratory disease (AERD) is thought to be based on, mainly, overproduction of eicosanoid lipid mediators and on defective anti-inflammatory regulators. Aspirin desensitization treatment, the mainstay of controlling asthma and rhinitis in AERD patients, however, is the least understood aspect of the disease. The study was designed to determine the effect of aspirin desensitization on T-lymphocyte cytokine expression and on plasma lipoxin levels in AERD. Spirometry, skin-prick test and asthma control test were documented and intracellular cytokine expression in T lymphocytes and plasma lipoxin levels were measured in 23 AERD patients, 17 aspirin-tolerant asthmatic (ATA) patients, and 16 healthy controls. In the AERD group nasal symptom and smell scores were assessed. Of the 23 AERD patients 15 accepted to undergo aspirin desensitization protocol and 14 of them were desensitized successfully. In the desensitized AERD group, cytokine and lipoxin measurements were repeated after 1-month aspirin treatment. CD4(+) IL-10 levels were higher in AERD patients than in healthy controls and CD4(+) interferon (IFN) gamma levels were higher in AERD and ATA patients than in controls. Plasma lipoxin-A4 and 15-epi-lipoxin-A4 levels were similar among the three study groups. In the AERD group, subjects underwent aspirin desensitization followed by a 1-month aspirin treatment. Clinical parameters improved and CD4(+) IFN-gamma levels decreased significantly. No significant change in lipoxin levels was recorded. CD4(+) IFN-gamma and CD4(+) IL-10 levels in AERD patients after 1-month aspirin desensitization treatment were similar to the healthy controls. The study confirms aspirin desensitization is effective clinically in AERD patients and suggests that IFN gamma and IL-10 expression in CD4(+) T lymphocytes may be related to the mechanism of action.

Aplikasi eye moving desensitization dan reprocessing dalam konseling post-traumatic stress disorder

OpenAIRE

Hengki Satrianta

2017-01-01

Akhir-akhir ini banyak peristiwa yang berpotensi memunculkan efek traumatik yang jika tidak ditangani akan menimbulkan gangguan stres pascatrauma. Olehnya itu, dibutuhkan upaya-upaya untu menangani masalah ini. Salah satu upaya yang dimaksud adalah penggunaan eye moving desensitization and reprocessing. Artikel ini ditulis dengan fokus pada penanganan gangguan stres pascatrauma melalui eye moving desensitization and reprocessing. Tujuan penulisan artikel ini adalah untuk mengetahui gambaran u...

B cell repertoires in HLA-sensitized kidney transplant candidates undergoing desensitization therapy.

Science.gov (United States)

Beausang, John F; Fan, H Christina; Sit, Rene; Hutchins, Maria U; Jirage, Kshama; Curtis, Rachael; Hutchins, Edward; Quake, Stephen R; Yabu, Julie M

2017-01-13

Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels. Responders to desensitization had a decrease of 5% points or greater in cumulated calculated panel reactive antibody (cPRA) levels, and non-responders had no decrease in cPRA. Dominant B cell clones were not observed in highly sensitized candidates, suggesting that the B cells responsible for sensitization are either not present in peripheral blood or present at comparable levels to other circulating B cells. Candidates that responded to desensitization therapy had pre-treatment repertoires composed of a larger fraction of class-switched (IgG and IgA) isotypes compared to non-responding candidates. After B cell depleting therapy, the proportion of switched isotypes increased and the mutation frequencies of the remaining non-switched isotypes (IgM and IgD) increased in both responders and non-responders, perhaps representing a shift in the repertoire towards memory B cells or plasmablasts. Conversely, after transplantation, non-switched isotypes with fewer mutations increased, suggesting a shift in the repertoire towards naïve B cells. Relative abundance of different B cell isotypes is strongly perturbed by desensitization therapy and transplantation, potentially reflecting changes in the relative

Rapid desensitization of adrenaline- and neuropeptide Y-stimulated Ca2+ mobilization in HEL-cells

NARCIS (Netherlands)

Michel, M. C.

1994-01-01

1. Desensitization of Gs-coupled receptors, the beta 2-adrenoceptor for example, involves rapid and slower components but little is known regarding the existence of rapid desensitization of Gi-coupled receptors and its possible mechanisms. In HEL-cells stimulation of alpha 2A-adrenoceptors by

A Comparison of Traditional and Self-Control Desensitization.

Science.gov (United States)

Deffenbacher, Jerry L.; Parks, Donald H.

1979-01-01

Compared effectiveness of counterconditioning and self-control models of systematic desensitization in reducing targeted and nontargeted anxieties. Treatments were equally effective in reducing and maintaining reduction of targeted anxiety, debilitating test anxiety. (Author)

A Comparison of Implosive Therapy and Systematic Desensitization in the Treatment of Test Anxiety

Science.gov (United States)

Smith, Ronald E.; Nye, S. Lee

1973-01-01

Both Desensitization and implosive therapy resulted in significant decreases in scores on Sarason's Test Anxiety Scale. However, the desensitization group also demonstrated a significant reduction in state anxiety assessed during simulated testing sessions and a significant increase in grade point average, while the implosive therapy group showed…

Specific oral desensitization in children with IgE-mediated cow's milk allergy. Evolution in one year.

Science.gov (United States)

Alvaro, Montserrat; Giner, Ma Teresa; Vázquez, Marta; Lozano, Jaime; Domínguez, Olga; Piquer, Mónica; Días, Marcia; Jiménez, Rosa; Martín, Ma Anunciación; Alsina, Laia; Plaza, Ana Ma

2012-09-01

Cow's milk allergy is the most frequent childhood food allergy. Children older than 5 who have not become tolerant have less probabilities of natural tolerance. Specific oral desensitization methods are being investigated in reference centres. The aims of our study were to assess the efficacy of our guideline of specific oral desensitization to cow's milk in children and to know its suitability for anaphylactic children. Both clinical and specific IgE outcomes were evaluated. Eighty-seven children aged 5 to 16 years with a history of cow's milk allergy were included. Prior to desensitization, skin prick test, specific IgE to cow's milk proteins and a double-blind placebo control food challenge were performed in all. Of the 87 patients, 21 had a negative challenge; they were considered tolerant, and they were told to follow a free diet. Of the positive, 44 were anaphylactic and 22 non-anaphylactic. All of them were included. In non-anaphylactic patients, 6 achieved partial and 16 maximum desensitization after 23.1 weeks. In the anaphylactic group, 7 achieved partial and 35 maximum desensitization after 26.4 weeks. Cow's milk-specific IgE levels and casein-specific IgE levels were significantly lower in the tolerant patients at baseline. One year after desensitization, the medium specific cow's milk levels and casein IgE levels had dropped significantly. Our guideline for specific oral desensitization to cow's milk is efficacious even in patients with anaphylactic reactions to cow's milk and represents a significant life change. Immunological changes in 1 year show a drop in cow's milk protein-specific IgE.

Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro

International Nuclear Information System (INIS)

Yang, Wei; Sun, Ting; Cao, Jianping; Liu, Fenju; Tian, Ye; Zhu, Wei

2012-01-01

Hypoxia is a common feature of solid tumors and an important contributor to tumor radioresistance. miR-210 is the most consistently and robustly induced microRNA under hypoxia in different types of tumor cells and normal cells. In the present study, to explore the feasibility of miR-210 as an effective therapeutic target, lentiviral-mediated anti-sense miR-210 gene transfer technique was employed to downregulate miR-210 expression in hypoxic human hepatoma SMMC-7721, HepG2 and HuH7 cells, and phenotypic changes of which were analyzed. Hypoxia led to an increased hypoxia inducible factor-1α (HIF-1α) and miR-210 expression and cell arrest in the G 0 /G 1 phase in all cell lines. miR-210 downregulation significantly suppressed cell viability, induced cell arrest in the G 0 /G 1 phase, increased apoptotic rate and enhanced radiosensitivity in hypoxic human hepatoma cells. Moreover, apoptosis-inducing factor, mitochondrion-associated, 3 (AIFM3) was identified as a direct target gene of miR-210. AIFM3 downregulation by siRNA attenuated radiation induced apoptosis in miR-210 downregulated hypoxic human hepatoma cells. Taken together, these data suggest that miR-210 might be a potential therapeutic target and specific inhibition of miR-210 expression in combination with radiotherapy might be expected to exert strong anti-tumor effect on hypoxic human hepatoma cells. -- Highlights: ► miR-210 downregulation radiosensitized hypoxic hepatoma. ► AIFM3 was identified as a direct target gene of miR-210. ► miR-210 might be a therapeutic target to hypoxic hepatoma.

Early aspirin desensitization in unstable patients with acute coronary syndrome: Short and long-term efficacy and safety.

Science.gov (United States)

Córdoba-Soriano, Juan Gabriel; Corbí-Pascual, Miguel; López-Neyra, Isabel; Navarro-Cuartero, Javier; Hidalgo-Olivares, Víctor; Barrionuevo-Sánchez, Maria Isabel; Prieto-Mateos, Daniel; Gutiérrez-Díez, Antonio; Gallardo-López, Arsenio; Fuentes-Manso, Raquel; Gómez-Pérez, Alberto; Lafuente-Gormaz, Carlos; Jiménez-Mazuecos, Jesús

2016-11-01

Aspirin hypersensitivity is not a rare condition among patients with acute coronary syndrome. However, despite the publication of several successful desensitization protocols, the procedure is not as widespread as expected. We present a cohort of patients with acute coronary syndrome undergoing aspirin desensitization to evaluate its short- and long-term efficacy and safety and to reinforce data from previous studies. Of 1306 patients admitted to our Coronary Care Unit between February 2011 and February 2013, 24 (1.8%) had a history of aspirin hypersensitivity. All 24 patients underwent an eight-dose aspirin desensitization protocol (0.1, 0.3, 1, 3, 10, 25, 50 and 100 mg of aspirin given by mouth every 15 minutes) after premedication with antihistamines and corticosteroids or antileucotrienes. Previously prescribed β blockers and angiotensin-converting enzyme inhibitors were not discontinued. All patients were desensitized within 72 hours of admission. Those requiring urgent catheterization (five patients with ST segment elevation myocardial infarction) were desensitized within 12 hours of catheterization and the remainder before catheterization. All patients were successfully desensitized and only one presented with an urticarial reaction. The five patients with ST segment elevation myocardial infarction were treated with abciximab until desensitization was complete. All but one patient underwent catheterization and 20 underwent percutaneous coronary intervention, most (66%) with the implantation of a bare metal stent. At follow-up (a minimum of 6-24 months), only two patients had discontinued aspirin, both due to gastrointestinal bleeding, and no hypersensitivy reaction had occurred. Aspirin desensitization is effective and safe in unstable patients with acute coronary syndrome in both the short and long term.

Niclosamide suppresses hepatoma cell proliferation via the Wnt pathway

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Tomizawa M

2013-11-01

Full Text Available Minoru Tomizawa,1 Fuminobu Shinozaki,2 Yasufumi Motoyoshi,3 Takao Sugiyama,4 Shigenori Yamamoto,5 Makoto Sueishi,4 Takanobu Yoshida6 1Department of Gastroenterology, 2Department of Radiology, 3Department of Neurology, 4Department of Rheumatology, 5Department of Pediatrics, 6Department of Internal Medicine, National Hospital Organization Shimoshizu Hospital, Yotsukaido City, Chiba, Japan Background: The Wnt pathway plays an important role in hepatocarcinogenesis. We analyzed the association of the Wnt pathway with the proliferation of hepatoma cells using Wnt3a and niclosamide, a drug used to treat tapeworm infection. Methods: We performed an MTS assay to determine whether Wnt3a stimulated proliferation of Huh-6 and Hep3B human hepatoma cell lines after 72 hours of incubation with Wnt3a in serum-free medium. The cells were subjected to hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL after 48 hours of incubation. RNA was isolated 48 hours after addition of Wnt3a or niclosamide, and cyclin D1 expression levels were analyzed by real-time quantitative polymerase chain reaction. The promoter activity of T-cell factor was analyzed by luciferase assay 48 hours after transfection of TOPflash. Western blot analysis was performed with antibodies against β-catenin, dishevelled 2, and cyclin D1. Results: Cell proliferation increased with Wnt3a. Niclosamide suppressed proliferation with or without Wnt3a. Hematoxylin and eosin and TUNEL staining suggested that apoptosis occurred in cells with niclosamide. Cyclin D1 was upregulated in the presence of Wnt3a and downregulated with addition of niclosamide. The promoter activity of T-cell factor increased with Wnt3a, whereas T-cell factor promoter activity decreased with niclosamide. Western blot analysis showed that Wnt3a upregulated β-catenin, dishevelled 2, and cyclin D1, while niclosamide downregulated them. Conclusion: Niclosamide is a potential

Desensitization And Study-Skills Training As Treatment For Two Types of Test-Anxious Students

Science.gov (United States)

Osterhouse, Robert A.

1972-01-01

This study compared the effectiveness of systematic desensitization and training in efficient study methods for reducing test anxiety among subjects selected on the basis of two types of self reported anxiety. Desensitization offered more promise as a treatment method for test anxiety than did training in study skills. (Author)

AMPA receptor mediated excitotoxicity in neocortical neurons is developmentally regulated and dependent upon receptor desensitization

DEFF Research Database (Denmark)

Jensen, J B; Schousboe, A; Pickering, D S

1998-01-01

with a fast and rapidly desensitizing response, this could explain the relatively low toxicity produced by 500 microM AMPA. This was investigated by blocking AMPA receptor desensitization with cyclothiazide. Using a lower concentration (25 microM) of AMPA, addition of 50 microM cyclothiazide increased...... the AMPA induced excitotoxicity in cultured cortical neurons at all DIV except for DIV 2. This combination of AMPA + cyclothiazide yielded 77% cell death for DIV 12 cultures. In contrast to the results observed with 500 microM AMPA, the neurotoxicity mediated directly by AMPA receptors when desensitization...

Characterising the mechanism of airway smooth muscle β2 adrenoceptor desensitization by rhinovirus infected bronchial epithelial cells.

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David Van Ly

Full Text Available Rhinovirus (RV infections account for approximately two thirds of all virus-induced asthma exacerbations and often result in an impaired response to β2 agonist therapy. Using an in vitro model of RV infection, we investigated the mechanisms underlying RV-induced β2 adrenoceptor desensitization in primary human airway smooth muscle cells (ASMC. RV infection of primary human bronchial epithelial cells (HBEC for 24 hours produced conditioned medium that caused β2 adrenoceptor desensitization on ASMCs without an effect on ASMCs viability. Less than 3 kDa size fractionation together with trypsin digestion of RV-induced conditioned medium did not prevent β2 adrenoceptor desensitization, suggesting it could potentially be mediated by a small peptide or lipid. RV infection of BECs, ASMCs and fibroblasts produced prostaglandins, of which PGE2, PGF2α and PGI2 had the ability to cause β2 adrenoceptor desensitization on ASMCs. RV-induced conditioned medium from HBECs depleted of PGE2 did not prevent ASMC β2 adrenoceptor desensitization; however this medium induced PGE2 from ASMCs, suggesting that autocrine prostaglandin production may be responsible. Using inhibitors of cyclooxygenase and prostaglandin receptor antagonists, we found that β2 adrenoceptor desensitization was mediated through ASMC derived COX-2 induced prostaglandins. Since ASMC prostaglandin production is unlikely to be caused by RV-induced epithelial derived proteins or lipids we next investigated activation of toll-like receptors (TLR by viral RNA. The combination of TLR agonists poly I:C and imiquimod induced PGE2 and β2 adrenoceptor desensitization on ASMC as did the RNA extracted from RV-induced conditioned medium. Viral RNA but not epithelial RNA caused β2 adrenoceptor desensitization confirming that viral RNA and not endogenous human RNA was responsible. It was deduced that the mechanism by which β2 adrenoceptor desensitization occurs was by pattern recognition receptor

[Ursodeoxycholic acid induced apoptosis of human hepatoma cells HepG2 and SMMC-7721 bymitochondrial-mediated pathway].

Science.gov (United States)

Wu, Duan; Zhou, Jianyin; Yin, Zhenyu; Liu, Pingguo; Zhao, Yilin; Liu, Jianming; Wang, Xiaomin

2014-12-02

To explore the effects and underlying mechanisms of ursodeoxycholic acid on human hepatoma cells. HepG2 and SMMC-7721 HCC cell lines were respectively treated with ursodeoxycholic acid. And cell proliferation, apoptosis and the expression of Bax/Bcl-2 gene were detected by methyl thiazolyl tetrazolium (MTT), inverted microscopy, fluorescent microscopy, flow cytometry and Western blot. Ursodeoxycholic acid significantly inhibited the proliferation of human hepatoma cells in a concentration- and time-dependent manner. The half maximal inhibitory concentrations (IC50) of HepG2 and SMMC-7721 were 397.3 and 387.7 µg/ml respectively after a 48-hour treatment of 400 µg /ml ursodeoxycholic acid. And it also induced the apoptosis of HepG2 and SMMC-7721 cells, up-regulated Bax gene and down-regulated Bcl-2 gene. Ursodeoxycholic acid inhibits the proliferation of hepatoma cells and induce apoptosis by mitochondrial-mediated pathway.

Clinicopathological study on the primary hepatoma of the atomic bomb survivors

Energy Technology Data Exchange (ETDEWEB)

Satoh, T; Takahara, O; Takahashi, N; Matsuo, K; Tsunoo, S [Nagasaki Atomic Bomb Hospital (Japan)

1978-09-01

Fifty-eight cases autopsied during 10 years from 1968 to 1977 were divided into (A) a non-exposed group, (B) a group exposed within 2 km of the center of explosion, and (C) a group exposed over 2 km from the center of explosion or a group who entered Nagasaki city after the explosion, and clinicopathological study on them was made in detail. These three groups were studied as to incidences according to age and sex, prognosis, histological types and hepatic lesion complicated by hepatoma in survival cases for more than one year, histological diagnosis, gross types, histological types, degree of atypia, hepatic lesion at sites not injured with hepatoma, and the detection rate of B-type virus hepatitis surface antigen (HBs-Ag). Pathohistologically, ordinary hematoxylin-eosin staining, van Gieson staining, silvering staining, iron staining were performed, and aldehyde-fuchsine staining was also performed HBs-Ag detection in a part of cases for.

Antibody Desensitization Therapy in Highly Sensitized Lung Transplant Candidates

Science.gov (United States)

Snyder, L. D.; Gray, A. L.; Reynolds, J. M.; Arepally, G. M.; Bedoya, A.; Hartwig, M. G.; Davis, R. D.; Lopes, K. E.; Wegner, W. E.; Chen, D. F.; Palmer, S. M.

2015-01-01

As HLAs antibody detection technology has evolved, there is now detailed HLA antibody information available on prospective transplant recipients. Determining single antigen antibody specificity allows for a calculated panel reactive antibodies (cPRA) value, providing an estimate of the effective donor pool. For broadly sensitized lung transplant candidates (cPRA ≥ 80%), our center adopted a pretransplant multimodal desensitization protocol in an effort to decrease the cPRA and expand the donor pool. This desensitization protocol included plasmapheresis, solumedrol, bortezomib and rituximab given in combination over 19 days followed by intravenous immunoglobulin. Eight of 18 candidates completed therapy with the primary reasons for early discontinuation being transplant (by avoiding unacceptable antigens) or thrombocytopenia. In a mixed-model analysis, there were no significant changes in PRA or cPRA changes over time with the protocol. A sub-analysis of the median fluorescence intensity (MFI) change indicated a small decline that was significant in antibodies with MFI 5000–10 000. Nine of 18 candidates subsequently had a transplant. Posttransplant survival in these nine recipients was comparable to other pretransplant-sensitized recipients who did not receive therapy. In summary, an aggressive multi-modal desensitization protocol does not significantly reduce pretransplant HLA antibodies in a broadly sensitized lung transplant candidate cohort. PMID:24666831

Outpatient rapid 4-step desensitization for gynecologic oncology patients with mild to low-risk, moderate hypersensitivity reactions to carboplatin/cisplatin.

Science.gov (United States)

Li, Quan; Cohn, David; Waller, Allyson; Backes, Floor; Copeland, Larry; Fowler, Jeffrey; Salani, Ritu; O'Malley, David

2014-10-01

The primary objective of this study is to assess the efficacy and safety of an outpatient, 4-step, one-solution desensitization protocol in gynecologic oncology patients with history of mild to low-risk, moderate hypersensitivity reactions (HSRs) to platinums (carboplatin and cisplatin). This was a single institutional retrospective review. Gynecologic oncology patients with a documented history of mild or low-risk, moderate immediate HSRs to carboplatin/cisplatin and continued treatment with 4-step, one-solution desensitization protocols in the outpatient infusion center were included. Patients with delayed HSRs or immediate high-risk, moderate or severe HSRs were excluded. The primary end point was the rate of successful administrations of each course of platinums. From January 2011 to June 2013, eighteen eligible patients were evaluated for outpatient 4-step, one-solution desensitization. Thirteen patients had a history of HSRs to carboplatin and 5 with HSRs to cisplatin. All of 18 patients successfully completed 94 (98.9%) of 95 desensitization courses in the outpatient infusion center. Eight of 8 (100%) patients with initial mild HSRs completed 29/29 (100%) desensitization courses, and 9 of 10 (90%) of patients with initial moderate HSRs completed 65/66 (94%) desensitization courses. In total, 65/95 (68%) desensitizations resulted in no breakthrough reactions, and mild, moderate and severe breakthrough reactions were seen in 19%, 12% and 1% desensitizations, respectively. No patients were hospitalized during desensitization. The outpatient rapid, 4-step, one-solution desensitization protocol was effective and appeared safe among gynecologic oncology patients who experienced mild to low-risk, moderate HSRs to carboplatin/cisplatin. Copyright © 2014 Elsevier Inc. All rights reserved.

Increasing access to kidney transplantation for sensitized recipient through three-way kidney paired donation with desensitization: The first Indian report

Science.gov (United States)

Kute, Vivek B; Patel, Himanshu V; Shah, Pankaj R; Modi, Pranjal R; Shah, Veena R; Rizvi, Sayyed J; Pal, Bipin C; Modi, Manisha P; Shah, Priya S; Varyani, Umesh T; Wakhare, Pavan S; Shinde, Saiprasad G; Ghodela, Viajay A; Patel, Minaxi H; Trivedi, Varsha B; Trivedi, Hargovind L

2016-01-01

The combination of kidney paired donation (KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation (LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT. PMID:27803919

Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Yang, Wei, E-mail: detachedy@yahoo.com.cn [Department of Radiobiology, School of Radiological Medicine and Protection, Soochow University, Suzhou (China); Sun, Ting [Brain and Nerve Research Laboratory, The First Affiliated Hospital, Soochow University, Suzhou (China); Cao, Jianping; Liu, Fenju [Department of Radiobiology, School of Radiological Medicine and Protection, Soochow University, Suzhou (China); Tian, Ye [Department of Radiotherapy and Oncology, The Second Affiliated Hospital, Soochow University, Suzhou (China); Zhu, Wei [Department of Radiobiology, School of Radiological Medicine and Protection, Soochow University, Suzhou (China)

2012-05-01

Hypoxia is a common feature of solid tumors and an important contributor to tumor radioresistance. miR-210 is the most consistently and robustly induced microRNA under hypoxia in different types of tumor cells and normal cells. In the present study, to explore the feasibility of miR-210 as an effective therapeutic target, lentiviral-mediated anti-sense miR-210 gene transfer technique was employed to downregulate miR-210 expression in hypoxic human hepatoma SMMC-7721, HepG2 and HuH7 cells, and phenotypic changes of which were analyzed. Hypoxia led to an increased hypoxia inducible factor-1{alpha} (HIF-1{alpha}) and miR-210 expression and cell arrest in the G{sub 0}/G{sub 1} phase in all cell lines. miR-210 downregulation significantly suppressed cell viability, induced cell arrest in the G{sub 0}/G{sub 1} phase, increased apoptotic rate and enhanced radiosensitivity in hypoxic human hepatoma cells. Moreover, apoptosis-inducing factor, mitochondrion-associated, 3 (AIFM3) was identified as a direct target gene of miR-210. AIFM3 downregulation by siRNA attenuated radiation induced apoptosis in miR-210 downregulated hypoxic human hepatoma cells. Taken together, these data suggest that miR-210 might be a potential therapeutic target and specific inhibition of miR-210 expression in combination with radiotherapy might be expected to exert strong anti-tumor effect on hypoxic human hepatoma cells. -- Highlights: Black-Right-Pointing-Pointer miR-210 downregulation radiosensitized hypoxic hepatoma. Black-Right-Pointing-Pointer AIFM3 was identified as a direct target gene of miR-210. Black-Right-Pointing-Pointer miR-210 might be a therapeutic target to hypoxic hepatoma.

Counselor-Subject Sex Variables in Systematic Desensitization

Science.gov (United States)

Geer, Carol A.; Hurst, James C.

1976-01-01

A Sex of Subject x Sex of Counselor interaction in the desensitization of test anxiety among 44 college students suggested consideration of the sex variable. Results showed significant treatment effects by both male and female counselors and a significant interaction effect by the male counselor with female subjects. (Author)

In vitro dentin permeability after application of Gluma® desensitizer as aqueous solution or aqueous fumed silica dispersion

Directory of Open Access Journals (Sweden)

Hiroshi Ishihata

2011-04-01

Full Text Available OBJECTIVES: To assess and to compare the effects of Gluma® Desensitizer (GDL with an experimental glutaraldehyde and HEMA containing fumed silica dispersion (GDG on dentin permeability using a chemiluminous tracer penetration test. MATERIAL AND METHODS: Twenty disc-shaped dentin specimens were dissected from extracted human third molars. The dentin specimens were mounted in a split chamber device for determination of permeability under liquid pressure using a photochemical method. Ten specimens were randomly selected and allocated to the evaluation groups Gluma® Desensitizer as aqueous solution and glutaraldehyde/HEMA as fumed silica dispersion, respectively. Dentin disc permeability was determined at two pressure levels after removal of smear with EDTA, after albumin soaking, and after application of the desensitizing agents. Two desensitizer-treated and rinsed specimens of each group were examined by scanning electron microscopy (SEM for surface remnants. RESULTS: Comparatively large standard deviations of the mean EDTA reference and albumin soaked samples permeability values refected the differences of the dentin substrates. The mean chemiluminescence values of specimen treated with GDL and GDG, respectively, were signifcantly reduced after topical application of the desensitizing agents on albumin-soaked dentin. The effects of GDL and GDG on permeability were not signifcantly different. Treated specimens showed no surface remnants after rinsing. CONCLUSIONS: The experimental desensitizer gel formulation reduced dentin permeability as effectively as the original Gluma® Desensitizer solution.

PPARα agonists up-regulate organic cation transporters in rat liver cells

International Nuclear Information System (INIS)

Luci, Sebastian; Geissler, Stefanie; Koenig, Bettina; Koch, Alexander; Stangl, Gabriele I.; Hirche, Frank; Eder, Klaus

2006-01-01

It has been shown that clofibrate treatment increases the carnitine concentration in the liver of rats. However, the molecular mechanism is still unknown. In this study, we observed for the first time that treatment of rats with the peroxisome proliferator activated receptor (PPAR)-α agonist clofibrate increases hepatic mRNA concentrations of organic cation transporters (OCTNs)-1 and -2 which act as transporters of carnitine into the cell. In rat hepatoma (Fao) cells, treatment with WY-14,643 also increased the mRNA concentration of OCTN-2. mRNA concentrations of enzymes involved in carnitine biosynthesis were not altered by treatment with the PPARα agonists in livers of rats and in Fao cells. We conclude that PPARα agonists increase carnitine concentrations in livers of rats and cells by an increased uptake of carnitine into the cell but not by an increased carnitine biosynthesis

Ulcerative colitis patients with an inflammatory response upon mesalazine cannot be desensitized: a randomized study.

Science.gov (United States)

Buurman, Dorien J; De Monchy, Jan G R; Schellekens, Reinout C A; van der Waaij, Laurens A; Kleibeuker, Jan H; Dijkstra, Gerard

2015-04-01

Mesalazine is a key drug in the treatment of ulcerative colitis (UC). Intolerance to mesalazine has been described, including fever and gastrointestinal symptoms. Several case reports reported successful desensitization of patients with mesalazine intolerance. The aim was to assess the number of UC patients who are persistently intolerant to mesalazine after single-blinded rechallenge and to test the effectiveness of a rapid desensitization protocol in UC patients demonstrated mesalazine intolerance. This is a prospective, single-blind randomized study in UC patients who discontinued mesalazine because of intolerance. Patients with severe reactions were excluded. Eligible patients underwent a skin patch test with mesalazine followed by a single-blinded randomized crossover rechallenge with 500 mg mesalazine or placebo. Patients with symptoms upon rechallenge were admitted to the hospital for 3 days oral desensitization. Nine of the 37 identified UC patients who discontinued mesalazine because of intolerance were included. All nine patients had negative patch tests, seven patients had symptoms (fever, nausea, vomiting and diarrhea) within 2 h upon rechallenge. Four of these seven patients participated in the desensitization protocol and in none a successful desensitization could be performed. All four had an inflammatory intolerance reaction with rise in C-reactive protein. There were no elevations in serum tryptase or urinary-methylhistamine levels observed and no signs of immediate type allergic reactions, like urticaria, bronchial obstruction or anaphylaxis. We recommend not to rechallenge UC patients with an inflammatory response upon mesalazine and these patients will not benefit from a rapid desensitization protocol.

Kidney paired exchange and desensitization: Strategies to transplant the difficult to match kidney patients with living donors.

Science.gov (United States)

Pham, Thomas A; Lee, Jacqueline I; Melcher, Marc L

2017-01-01

With organs in short supply, only a limited number of kidney transplants can be performed a year. Live donor donation accounts for 1/3rd of all kidney transplants performed in the United States. Unfortunately, not every donor recipient pair is feasible because of Human leukocyte antigen (HLA) sensitization and ABO incompatibility. To overcome these barriers to transplant, strategies such as kidney paired donation (KPD) and desensitization have been developed. KPD is the exchange of donors between at least two incompatible donor-recipient pairs such that they are now compatible. Desensitization is the removal of circulating donor specific antibodies to prevent graft rejection. Regardless of the treatment strategy, highly sensitized patients whose calculated panel reactive antibody (cPRA) is ≥95% remain difficult to transplant with match rates as low as 15% in KPD pools. Desensitization has proved to be difficult in those with high antibody titers. A novel approach is the combination of both KPD and desensitization to facilitate compatible and successful transplantation. A highly sensitized patient can be paired with a better immunological match in the KPD pool and subsequently desensitized to a lesser degree. This article reviews the current progress in KPD and desensitization and their use as a combined therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Desensitization Protocol in Recipients of Deceased Kidney Donor With Donor-Specific Antibody-Low Titers.

Science.gov (United States)

Kanter Berga, J; Sancho Calabuig, A; Gavela Martinez, E; Puig Alcaraz, N; Avila Bernabeu, A; Crespo Albiach, J; Molina Vila, P; Beltrán Catalan, S; Pallardó Mateu, L

2016-11-01

Kidney transplantation is the better option for end-stage renal disease (ESRD), but for patients with human leukocyte antigen (HLA) sensitization, the wait times are significantly longer than for patients without antibodies. Many desensitization protocols have been described involving strong immunosuppression, the use of apheresis, and B-cell-modulating therapies. We have designed a desensitization protocol from day 0 for deceased donor kidney transplantation. Our aim was to present our initial experience with five kidney transplant patients. All patients had a negative complement-dependent cytotoxicity cross-match. The desensitization protocol included five to seven doses of thymoglobulin (1.25 mg/kg) and three sessions of plasmapheresis (PP) within the first week after transplantation, with intravenous immunoglobulin (500 mg/kg) after each PP session and one dose of rituximab on day 8. The presence of donor-specific antibodies (DSA) was analyzed by use of Luminex technology; levels between 1000 and 3000 mean fluorescence intensity were considered for desensitization. The median age was 44 years and median renal replacement therapy time was 9 years. All recipients presented 1 to 3 DSA specificities. There were no severe side effects related to PP, infusion of intravenous immunoglobulin, or rituximab. The median follow-up period was 19.3 months. Median serum creatinine level at last follow-up was 1.7 mg/dL. A kidney biopsy was performed in all patients. Graft and patient survival was 100%. Until now, few data are available concerning whether HLA-incompatible kidney transplantation after desensitization would benefit patients with ERSD. The desensitization strategy using the combination of PP, low doses of intravenous immunoglobulin, and rituximab at our center resulted in a satisfactory clinical outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Localization of 131I-chTNT in a nude mice model with human hepatoma

International Nuclear Information System (INIS)

Chen Shaoliang; Sun Xiaoguang; Xiu Yan; Zhong Gaoren; Qiao Weiwei; Xu Lanwen; Li Wenzheng

1998-01-01

Purpose: In order to evaluate the targeting activity in the animal model with human hepatoma, the 131 I-chTNT radioimmunoimaging was explored. Methods: Radioimmunoimages were taken on different intervals after injection of 131 I-chTNT 5.55 MBq to the nude mice, and tissue distribution was measured. The results of 131 I-chTNT monoclonal antibody group were compared with that of 131 I control group. Results: The experimental group developed tumor positive images after one day of radio-labelled monoclonal antibodies injection and held on until the end of the experiment. The radioactivity in tumor mass was stable, and the half life of 131 I-chTNT in hepatoma mass was 6.0 +- 1.6 days. there was no special radioactivity accumulation in normal liver tissue in the nude mice and the radioactivity in it disappeared rapidly. Statistics indicated the tumor/liver ratio in 1, 2, 3, 5, 7 days were 1.03, 2.43, 5.71, 7.96, 10.67, respectively. Conclusions: The results suggest that 131 I-chTNT monoclonal antibody has a considerable targeting activity, and provide an evidence for that it can be used as a new radiopharmaceutical agent for the imaging and radio therapy of hepatoma

The Effect of Self and In Vivo Desensitization on Counselor Trainee Anxiety and Performance.

Science.gov (United States)

Miller, Thomas V.

The rationale, planning and implementing of this research is discussed in terms of its three hypotheses: (1) that both self desensitization and in vivo desensitization would result in lower Fear Index and Anxiety Differential scores of counselor trainees just prior to communicating with a role playing client in a counseling room where they are…

Psychodynamic Emotional Regulation in View of Wolpe's Desensitization Model.

Science.gov (United States)

Rabinovich, Merav

2016-01-01

The current research belongs to the stream of theoretical integration and establishes a theoretical platform for integrative psychotherapy in anxiety disorders. Qualitative metasynthesis procedures were applied to 40 peer-reviewed psychoanalytic articles involving emotional regulation. The concept of psychodynamic emotional regulation was found to be connected with the categories of desensitization, gradual exposure, containment, and transference. This article presents a model according to which psychoanalytic psychotherapy allows anxiety to be tolerated while following the core principles of systematic desensitization. It is shown that despite the antiresearch image of psychoanalytic psychotherapy, its foundations obey evidence-based principles. The findings imply that anxiety tolerance might be a key goal in which the cumulative wisdom of the different therapies can be used to optimize psychotherapy outcomes.

Studies on Anti-Hepatoma Effect of Gan-Ai-Xiao Decoction | Yuan ...

African Journals Online (AJOL)

Purpose: To explore the anti-hepatoma effect of Gan-Ai-Xiao Decoction (GAXD), a folk remedy. Methods: High performance liquid chromatography (HPLC) was used to identify the major chemical components of GAXD ethanol extract (EE). The cytotoxic effect of GAXD EE against HepG2 cells was measured by methyl ...

4-step 4-h carboplatin desensitization protocol for patients with gynecological malignancies showing platinum hypersensitivity: a retrospective study.

Science.gov (United States)

Takase, Naoto; Matsumoto, Koji; Onoe, Takuma; Kitao, Akihito; Tanioka, Maki; Kikukawa, Yoshitaka; Yamaguchi, Satoshi; Fujiwara, Kiyoshi; Negoro, Shunichi

2015-06-01

Platinum agents are essential for treating gynecological malignancies, particularly ovarian cancer. However, multiple carboplatin doses may cause hypersensitivity reactions (HSRs). Carboplatin desensitization prevents life-threatening HSRs and promotes the successful completion of planned chemotherapy. Since January 2010, carboplatin desensitization was performed at our institution. Solutions with 1/1000, 1/100, and 1/10 dilutions of carboplatin and an undiluted solution were prepared in 250 mL of 5% glucose. Each solution was administered as a 1-h intravenous infusion (4-step 4-h protocol). This retrospective analysis was approved by the institutional review board. From January 2010 to December 2013, 20 patients with gynecological malignancies (median age 62 years, range 43-74 years) received desensitization treatment. The International Federation of Gynecology and Obstetrics stages at presentation were I, II, III, and IV in 1, 1, 15, 13 patients, respectively. During first-line and second-line treatments, 3 and 17 patients, respectively, experienced carboplatin-induced HSRs. The median carboplatin cycle number was 11 (range 2-16). In the first desensitization cycle, 17 (85%) patients completed treatment without adverse events, 2 experienced Grade 1 HSRs but completed treatment, and 1 experienced Grade 3 HSR and discontinued treatment. The first desensitization cycle completion rate was 95%. Of 83 desensitization cycles administered, 79 (95.2%) were completed. No treatment-related deaths occurred. Most patients completed the planned chemotherapy. Our protocol could be conducted safely with shorter duration and simpler procedures than previous protocols. Carboplatin desensitization seems beneficial for patients with a history of carboplatin-induced HSRs; however, the risk of HSR recurrence still remains. Desensitization should therefore be performed only by well-trained staff.

Comparison of Three Methods of Reducing Test Anxiety: Systematic Desensitization, Implosive Therapy, and Study Counseling

Science.gov (United States)

Cornish, Richard D.; Dilley, Josiah S.

1973-01-01

Systematic desensitization, implosive therapy, and study counseling have all been effective in reducing test anxiety. In addition, systematic desensitization has been compared to study counseling for effectiveness. This study compares all three methods and suggests that systematic desentization is more effective than the others, and that implosive…

Comparison of Relaxation as Self-control and Systematic Desensitization in the Treatment of Test Anxiety

Science.gov (United States)

Snyder, Arden L.; Deffenbacher, Jerry L.

1977-01-01

Relaxation as self-control and desensitization were compared to a wait-list control in reduction of rest and other anxieties. Active treatments differed significantly from the control treatment. Subjects in both treatments reported less debilitating test anxiety, whereas desensitization subjects showed greater facilitating test anxiety. (Author)

REM Desensitization as a New Therapeutic Method for Post- Traumatic Stress Disorder: A Randomized Controlled Trial

Directory of Open Access Journals (Sweden)

Khodabakhsh Ahmadi

2016-05-01

Full Text Available Aim: to evaluate potential efficacy of a new therapeutic approach in posttraumatic stress disorder in comparison with eye movement desensitization and reprocessing (EMDR, a standard treatment approach and controls. Methods: the study was designed using a randomized controlled trial methodology. Participants were recruited from military servicemen aged between 25 to 50 years who were admitting hospitals of Bushehr, Iran, with the final diagnosis of PTSD. Finally 33 male patients were devided into three subgroups: G1: EMDR; G2: REM Desensitization; and group 3: controls who received no therapy. Mississippi Scale for Posttraumatic Stress Disorder, Pittsburgh Sleep Quality Index (PSQI and a 37 item death anxiety questionnaire were used for measures. Results: multiple comparisons showed that intrusive thoughts were significantly more likely to improve with REM Desensitization versus EMDR (P=0.03, while depression was more responsive to EMDR (p=0.03. Among the Pittsburgh scale for the quality of sleep items, sleep quality (p=0.02, sleep duration (p=0.001, and total sleep quality score (p=0.002 were significantly more likely to improve in the REM Desensitization group. Change in the absolute death anxiety scores was not different between subgroups excepting EMDR versus control group (p=0.05. Conclusion: REM, desensitization, the new therapeutic approach to PTSD is a highly effective strategy, even more than EMDR, the standard treatment, in most of the evaluated subjects, with special emphasis on sleep symptoms, and also in the management of intrusive thoughts. Depression is the only factor in which, REM Desensitization was significantly less likely to represent a superior therapeutic effect than EMDR. Key words: post traumatic stress disorder (PTSD, eye movement desensitization and reprocessing, new treatment.

A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients.

Science.gov (United States)

Schneider, Lynda C; Rachid, Rima; LeBovidge, Jennifer; Blood, Emily; Mittal, Mudita; Umetsu, Dale T

2013-12-01

Peanut allergy is a major public health problem that affects 1% of the population and has no effective therapy. To examine the safety and efficacy of oral desensitization in peanut-allergic children in combination with a brief course of anti-IgE mAb (omalizumab [Xolair]). We performed oral peanut desensitization in peanut-allergic children at high risk for developing significant peanut-induced allergic reactions. Omalizumab was administered before and during oral peanut desensitization. We enrolled 13 children (median age, 10 years), with a median peanut-specific IgE level of 229 kU(A)/L and a median total serum IgE level of 621 kU/L, who failed an initial double-blind placebo-controlled food challenge at peanut flour doses of 100 mg or less. After pretreatment with omalizumab, all 13 subjects tolerated the initial 11 desensitization doses given on the first day, including the maximum dose of 500 mg peanut flour (cumulative dose, 992 mg, equivalent to >2 peanuts), requiring minimal or no rescue therapy. Twelve subjects then reached the maximum maintenance dose of 4000 mg peanut flour per day in a median time of 8 weeks, at which point omalizumab was discontinued. All 12 subjects continued on 4000 mg peanut flour per day and subsequently tolerated a challenge with 8000 mg peanut flour (equivalent to about 20 peanuts), or 160 to 400 times the dose tolerated before desensitization. During the study, 6 of the 13 subjects experienced mild or no allergic reactions, 5 subjects had grade 2 reactions, and 2 subjects had grade 3 reactions, all of which responded rapidly to treatment. Among children with high-risk peanut allergy, treatment with omalizumab may facilitate rapid oral desensitization and qualitatively improve the desensitization process. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Evolving paradigms for desensitization in managing broadly HLA sensitized transplant candidates.

Science.gov (United States)

Reinsmoen, Nancy L; Lai, Chi-Hung; Vo, Ashley; Jordan, Stanley C

2012-04-01

The broadly human leukocyte antigen (HLA) sensitized patient awaiting organ transplantation remains a persistent and significant problem for transplant medicine. Sensitization occurs as a consequence of exposure to HLA antigens through pregnancy, blood and platelet transfusions, and previous transplants. Early experience with desensitization protocols coupled with improved diagnostics for donor-specific antibodies (DSAs) and renal pathology have greatly improved transplant rates and outcomes for patients once considered un-transplantable or at high risk for poor outcomes. More recent advances have occurred through implementation of a national allocation system requiring the entering of unacceptable antigens that reduces the rate of crossmatch positivity. Current desensitization therapies include high-dose intravenous immunoglobulin (IVIG), plasma exchange (PLEX) with low-dose IVIG, and IVIG combined with rituximab. Developing therapies include proteasome inhibitors aimed at plasma cells and modifiers of complement-mediated injury. Here we discuss the important advancements in desensitization including defining the risk for antibody-mediated rejection prior to transplantation and the evolution of therapies aimed at reducing the impact of antibody injury on allografts.

Desensitizing Addiction : Using Eye Movements to Reduce the Intensity of Substance-Related Mental Imagery and Craving

NARCIS (Netherlands)

Littel, M.; van den Hout, M.A.; Engelhard, I.M.

2016-01-01

Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. During this treatment, patients recall traumatic memories while making horizontal eye movements (EM). Studies have shown that EM not only desensitize negative memories but also positive

Outcomes of Highly Sensitized Patients Undergoing Simultaneous Liver and Kidney Transplantation: A Single-Center Experience With Desensitization.

Science.gov (United States)

Steggerda, J A; Kang, A; Pan, S-H; Sundaram, V; Nissen, N N; Klein, A S; Todo, T; Annamalai, A; Vo, A; Jordan, S C; Kim, I K

Preformed donor-specific human leukocyte antigen antibodies (DSAs) in patients undergoing simultaneous liver and kidney transplantation (SLKT) are an independent risk factor for poorer patient and renal allograft survival. The outcomes of patients highly sensitized (HS) against HLA antigens undergoing SLKT and select HS SLKT recipients undergoing desensitization at a high-volume desensitization center were investigated. Seventy-five patients undergoing SLKT at a high-volume desensitization center between January 1, 2001, and December 31, 2015, were retrospectively reviewed. HS patients were defined by panel-reactive antibody (PRA) >30% (n = 17 patients), 11 of whom received pre- or perioperative desensitization with high-dose intravenous immunoglobulin (IVIG) ± rituximab. HS patients had significantly higher class I and class II PRA (class I = 41.3% ± 40.0% vs 2.5% ± 6.3%; class II = 45.7% ± 36.4% vs 1.0% ± 2.9%; P Desensitization in select HS SLKT patients was well tolerated but did not improve patient and allograft survival or significantly curtail rejection. HS SLKT recipients demonstrated increased allograft rejection, particularly CMR, but patient and graft survival were not impacted in the first year post-transplant. Select HS SLKT patients tolerated desensitization with high-dose IVIG ± rituximab and may have received additional immunoprotection against ABMR but survival was not affected. Copyright © 2017 Elsevier Inc. All rights reserved.

Excessive users of violent video games do not show emotional desensitization: an fMRI study.

Science.gov (United States)

Szycik, Gregor R; Mohammadi, Bahram; Hake, Maria; Kneer, Jonas; Samii, Amir; Münte, Thomas F; Te Wildt, Bert T

2017-06-01

Playing violent video games have been linked to long-term emotional desensitization. We hypothesized that desensitization effects in excessive users of violent video games should lead to decreased brain activations to highly salient emotional pictures in emotional sensitivity brain regions. Twenty-eight male adult subjects showing excessive long-term use of violent video games and age and education matched control participants were examined in two experiments using standardized emotional pictures of positive, negative and neutral valence. No group differences were revealed even at reduced statistical thresholds which speaks against desensitization of emotion sensitive brain regions as a result of excessive use of violent video games.

Alpha-feto protein radioimmunoassay and its values for the diagnosis of hepatoma among normal Japanese population and those with chronic schistosomiasis

International Nuclear Information System (INIS)

Lio, Masahiro; Yamada, Hideo; Luchi, Masahiko

1972-01-01

Since its first report made by Ablevet al., α-feto protein which appears both in fetal serum and serum in the cases with hepatoma drew attention of hepatologist in order to establish an qualitative method to diagnose the presence of hepatoma. Since conventional liver scintigraphy is not able to make the diagnosis of the nature of lesion which appears as space occupying lesion need for the more qualitative method facilitated the establishment of the method to detect the presence of α-feto protein in serum. α-feto protein in the serum of hepatoma cases was reported to be identical to fetal α-feto protein by the immunological method. At first, assay of the α-feto protein was performed using the precipitation reaction in agar gel and became quite popular among clinical hepatologist. Detection sensitivity of this conventional method, however, is approximately 10 μgr/ml and α-feto protein was detected in 80% of hepatoma patient. However detection percentage of the hepatoma cases associated with chronic schistosomiasis was found to be as poor as 30% which was measured by our group at Kofu municipal Hospital. Because of the frequent incidences of deformed and small liver by scintigraphy among cases with chronic schistosomiasis and these abnormal liver scintigraphy easily lead one to middiagnose the presence of hepatoma, establishment of more sensitive assay method is needed. After the success of purification and crystallization of the α-feto protein by the group of Univ. of Hokkaido, the radioimmunoassay technique was developed in Japan and α-feto-125 Kit is now became available commercially. Initial trial of this new promising and this double antibody technique enabled us to measure 2 mμgr/ml of α-feto protein which was almost 500-1,000 times more sensitive than those of the conventional method.

Desensitization and recovery of metastable intermolecular composites

Science.gov (United States)

Busse, James R [South Fork, CO; Dye, Robert C [Los Alamos, NM; Foley, Timothy J [Los Alamos, NM; Higa, Kelvin T [Ridgecrest, CA; Jorgensen, Betty S [Jemez Springs, NM; Sanders, Victor E [White Rock, NM; Son, Steven F [Los Alamos, NM

2010-09-07

A method to substantially desensitize a metastable intermolecular composite material to electrostatic discharge and friction comprising mixing the composite material with an organic diluent and removing enough organic diluent from the mixture to form a mixture with a substantially putty-like consistency, as well as a concomitant method of recovering the metastable intermolecular composite material.

Prospective iterative trial of proteasome inhibitor-based desensitization.

Science.gov (United States)

Woodle, E S; Shields, A R; Ejaz, N S; Sadaka, B; Girnita, A; Walsh, R C; Alloway, R R; Brailey, P; Cardi, M A; Abu Jawdeh, B G; Roy-Chaudhury, P; Govil, A; Mogilishetty, G

2015-01-01

A prospective iterative trial of proteasome inhibitor (PI)-based therapy for reducing HLA antibody (Ab) levels was conducted in five phases differing in bortezomib dosing density and plasmapheresis timing. Phases included 1 or 2 bortezomib cycles (1.3 mg/m(2) × 6-8 doses), one rituximab dose and plasmapheresis. HLA Abs were measured by solid phase and flow cytometry (FCM) assays. Immunodominant Ab (iAb) was defined as highest HLA Ab level. Forty-four patients received 52 desensitization courses (7 patients enrolled in multiple phases): Phase 1 (n = 20), Phase 2 (n = 12), Phase 3 (n = 10), Phase 4 (n = 5), Phase 5 (n = 5). iAb reductions were observed in 38 of 44 (86%) patients and persisted up to 10 months. In Phase 1, a 51.5% iAb reduction was observed at 28 days with bortezomib alone. iAb reductions increased with higher bortezomib dosing densities and included class I, II, and public antigens (HLA DRβ3, HLA DRβ4 and HLA DRβ5). FCM median channel shifts decreased in 11/11 (100%) patients by a mean of 103 ± 54 mean channel shifts (log scale). Nineteen out of 44 patients (43.2%) were transplanted with low acute rejection rates (18.8%) and de novo DSA formation (12.5%). In conclusion, PI-based desensitization consistently and durably reduces HLA Ab levels providing an alternative to intravenous immune globulin-based desensitization. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Regulatory elements in the promoter region of the rat gene encoding the acyl-CoA-binding protein

DEFF Research Database (Denmark)

Elholm, M; Bjerking, G; Knudsen, J

1996-01-01

for the ACBP DR-1 element. Addition of peroxisome proliferators (PP) to H4IIEC3 rat hepatoma cells led to an increase in the ACBP mRNA level, indicating that the DR-1 element could be a functional peroxisome proliferator responsive element (PPRE). Analysis of the ACBP promoter by transient transfection showed...

Voltage quality: solutions of desensitization; Qualite de la tension: les solutions de desensibilisation

Energy Technology Data Exchange (ETDEWEB)

Anon.

1999-10-01

The occurrence of voltage drops and cuts can lead to major malfunctions in electrical installations with sometimes important economical impacts. Thus, the use of solutions of desensitization are needed to avoid such disturbances. This technical paper gives a summary of the basic solutions elaborated by Electricite de France (EdF) with the participation of electrical engineering associations in order to solve the problems encountered in existing installations and to provide specifications for the newly designed installations: the desensitization process (origin of voltage drops, solutions, costs), the diagnosis of industrial installations (identification, quantitative analysis and recording of disturbances, complementary informations, causes, economical impact, solutions, costs, remedial action), the general and specific solutions of desensitization (instrumentation and control systems, switches, relays, motors, speed regulators and variators), specific solutions for computerized and electronic systems, and the role of batteries. (J.S.)

Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

Energy Technology Data Exchange (ETDEWEB)

Singaravelu, Ragunath [Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Lyn, Rodney K. [Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Srinivasan, Prashanth [National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Delcorde, Julie [Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Steenbergen, Rineke H.; Tyrrell, D. Lorne [Department of Medical Microbiology and Immunology, University of Alberta (Canada); Li Ka Shing Institute of Virology, Katz Centre for Pharmacy and Health Research, Edmonton, Alberta T6G 2S2 (Canada); Pezacki, John P., E-mail: John.Pezacki@nrc-cnrc.gc.ca [Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada)

2013-11-15

Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway.

Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

International Nuclear Information System (INIS)

Singaravelu, Ragunath; Lyn, Rodney K.; Srinivasan, Prashanth; Delcorde, Julie; Steenbergen, Rineke H.; Tyrrell, D. Lorne; Pezacki, John P.

2013-01-01

Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway

Outcome after Desensitization in HLA or ABO-Incompatible Kidney Transplant Recipients: A Single Center Experience.

Science.gov (United States)

Kauke, Teresa; Klimaschewski, Sandra; Schoenermarck, Ulf; Fischereder, Michael; Dick, Andrea; Guba, Markus; Stangl, Manfred; Werner, Jens; Meiser, Bruno; Habicht, Antje

2016-01-01

The shortage of deceased donors led to an increase of living donor kidney (LDK) transplantations performed in the presence of donor-specific antibodies (DSA) or ABO incompatibility (ABOi) using various desensitization protocols. We herein analyzed 26 ABOi and 8 Luminex positive DSA patients who were successfully desensitized by anti-CD20, antigen-specific immunoadsorption and/or plasmapheresis to receive an LDK transplant. Twenty LDK recipients with non-donor-specific HLA-antibodies (low risk) and 32 without anti-HLA antibodies (no risk) served as control groups. 1-year graft survival rate and renal function was similar in all 4 groups (creatinine: 1.63 ± 0.5 vs 1.78 ± 0.6 vs 1.64 ± 0.5 vs 1.6 ± 0.3 mg/dl in ABOi, DSA, low risk and no risk group). The incidence of acute T-cell mediated rejections did not differ between the 4 groups (15% vs 12, 5% vs 15% vs 22% in ABOi, DSA, low risk and no risk), while antibody-mediated rejections were only found in the DSA (25%) and ABOi (7.5%) groups. Incidence of BK nephropathy (BKVN) was significantly more frequent after desensitization as compared to controls (5/34 vs 0/52, p = 0.03). We demonstrate favorable short-term allograft outcome in LDK transplant recipients after desensitization. However, the desensitization was associated with an increased risk of BKVN.

Desensitizing Children's Emotional Reactions to the Mass Media.

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Wilson, Barbara J.

1989-01-01

Assesses effectiveness of two desensitization strategies for reducing children's emotional reactions to mass media. Examines children having passive exposure, modeled exposure, or no exposure to lizards before watching a horror movie involving lizards. Finds that modeled exposure decreases emotional reactions and negative interpretations, whereas…

A role for inflammatory mediators in heterologous desensitization of CysLT1 receptor in human monocytes

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Capra, Valérie; Accomazzo, Maria Rosa; Gardoni, Fabrizio; Barbieri, Silvia; Rovati, G. Enrico

2010-01-01

Cysteinyl-leukotrienes (cysteinyl-LT) are rapidly generated at sites of inflammation and, in addition to their role in asthma, rhinitis, and other immune disorders, are increasingly regarded as significant inflammatory factors in cancer, gastrointestinal, cardiovascular diseases. We recently demonstrated that in monocyte/macrophage–like U937 cells, extracellular nucleotides heterologously desensitize CysLT1 receptor (CysLT1R)-induced Ca2+ transients. Given that monocytes express a number of other inflammatory and chemoattractant receptors, this study was aimed at characterizing transregulation between these different stimuli. We demonstrate that in U937 cells and in primary human monocytes, a series of inflammatory mediators activating Gi-coupled receptor (FPR1, BLT1) desensitize CysLT1R-induced Ca2+ response unidirectionally through activation of PKC. Conversely, PAF-R, exclusively coupled to Gq, cross-desensitizes CysLT1R without the apparent involvement of any kinase. Interestingly, Gs-coupled receptors (β2AR, H1/2R, EP2/4R) are also able to desensitize CysLT1R response through activation of PKA. Heterologous desensitization seems to affect mostly the Gi-mediated signaling of the CysLT1R. The hierarchy of desensitization among agonists may be important for leukocyte signal processing at the site of inflammation. Considering that monocytes/macrophages are likely to be the major source of cysteinyl-LT in many immunological and inflammatory processes, shedding light on how their receptors are regulated will certainly help to better understand the role of these cells in orchestrating this complex network of integrated signals. PMID:19965602

Radiosensitizing effects of 9401 on mice bearing H22 hepatoma

International Nuclear Information System (INIS)

Liu Xiaoqiu; Wang Qin; Zhou Zewei; Han Ying; Wang Dezhi; Shen Xiu

2013-01-01

Objective: To investigate the radiosensitizing effects of 9401 on mice bearing H22 hepatoma. Methods: Mouse model bearing H22 hepatoma cells were established. Mice were randomly divided into six groups, the control group,the radiation group and four treatment groups including 9401 at high, medium and low dosages and nicotinamide combined with radiation. After irradiated, the growth of tumor was observed, the time of tumor growth was recorded, the delay time of tumor growth and enhancement factor (EF) were calculated. After 28 days, the mice were killed, the tumors were stripped and inhibition rate was calculated. Results: Groups of 9401 combined with radiation could postpone tumor growth. The difference was statistically significant between 9401 groups at high, medium dosages combined with radiation and nicotinamide combined with radiation group (t=24.7 and 7.5, both P<0.01). Compared with radiation alone group, groups of 9401 combined with radiation had significant radiosensitizing effect. The enhancement factor of 9401 combined with radiation groups at high and medium dosages were 2.13 and 1.73 respectively, they were significant higher than nicotinamide combined with radiation group (t=2.26 and 9.04, both P<0.05). The inhibition rate of 9401 groups at high, medium and low dosages combined with radiation were 64.5%, 50.9% and 42.6% respectively. The inhibition rate of nicotinamide group combined radiation was 53.2%. The inhibition rate of 9401 at high dosage combined with radiation had significant difference with nicotinamide combined radiation (t =2.8, P<0.05). Nicotinamide combined with radiation group, 9401 combined with radiation groups could significant inhibit the growth of tumors compared with radiation alone group (t=5.7, 4.0 and 2.2, all P<0.05). Conclusion: 9401 can inhibit the tumor growth and the inhibition effect increases gradually with the drug dose increasing. It also has radiosensitizing effects on mice bearing H22 hepatoma and present broadly

Comparison of Anxiety Management Training and Self-Control Desensitization.

Science.gov (United States)

Deffenbacher, Jerry L.; And Others

1980-01-01

Anxiety management training and self-control desensitization effectively reduced debilitating test anxiety and increased facilitating test anxiety. Follow-up demonstrated maintenance of debilitating test anxiety reduction. Subjects receiving treatment had significantly higher psychology grades. (Author)

Human leukocyte antigen genotypes and trial of desensitization in patients with oxcarbazepine-induced skin rash: a pilot study.

Science.gov (United States)

Lee, Bolyun; Yu, Hee Joon; Kang, Eun-Suk; Lee, Munhyang; Lee, Jeehun

2014-08-01

Skin rash associated with specific antiepileptic drugs occurs not infrequently and it usually necessitates discontinuation of the causative drugs. An alternative strategy is to desensitize the individual to the offending drug. We checked the human leukocyte antigen genotypes and conducted a pilot study to investigate the usefulness and safety of desensitization in pediatric patients with skin rash associated with oxcarbazepine. We enrolled 19 patients with epilepsy who had discontinued oxcarbazepine because of skin rash despite an initial good response and then became refractory to other antiepileptic drugs along with an individual with paroxysmal kinesigenic dyskinesia with a similar situation. High-resolution HLA-A and -B genotyping was performed to investigate the genetic risk. The desensitization began with 0.1 mg daily reaching 120 mg on the thirty-first day. Thereafter, the dose was increased at a rate of 12 mg/day. Nineteen patients completed the desensitization protocol to a target dosage over 2-5 months. Five patients developed itching and erythema during desensitization, but the symptoms disappeared after withholding a dose increment transiently. There were no human leukocyte antigen genotypes relevant to aromatic antiepileptic drug-induced severe hypersensitivity reactions. The seizure frequency was reduced to less than at baseline in 18 individuals. This study demonstrated 95% efficacy, including 42% seizure-free patients and the favorable tolerability of desensitization to oxcarbazepine in patients with intractable epilepsy and one patient with paroxysmal kinesigenic dyskinesia. Screening for sensitive human leukocyte antigen types and exclusion of severe hypersensitivity reactions should precede desensitization. Copyright © 2014 Elsevier Inc. All rights reserved.

Aspirin allergy desensitization in cerebrovascular disease. A report of two cases, literature review and management guide for the neurointerventionalist.

Science.gov (United States)

Zuckerman, Scott L; Seder, David B; Tsujiura, Crystiana; Cushing, Deborah; Gallup, Holly; Mocco, J; Hanel, Richard A; Ecker, Robert D

2014-01-01

Aspirin (ASA) is the mainstay of treatment in cerebrovascular and systemic vascular disease. ASA hypersensitivity can pose a challenge to achieving optimum medical management prior to and after neurointerventional treatment. Desensitization to ASA is well described in the allergy and cardiovascular literature, but there are no similar discussions specific to neurointervention. The purpose of our study was to describe our experience with ASA hypersensitivity management and review the relevant literature. Two cases of patients with symptomatic cerebrovascular disease requiring neurointervention who were successfully desensitized to their ASA hypersensitivity prior to treatment are described. The subsequent literature is reviewed. Several ASA desensitization protocols exist and have been proven to successfully treat ASA hypersensitivity and allow for ASA therapy to be safely initiated. We describe several previously published protocols. ASA desensitization is a safe and simple way to manage ASA hypersensitivity. We provide comprehensive management guidelines for the neurointerventionalist engaging in ASA desensitization.

A comparative evaluation of the effect of dentin desensitizers on the retention of complete cast metal crowns

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Saili M Chandavarkar

2015-01-01

Full Text Available Context: Desensitizers are used to reduce dentin hypersensitivity. They affect the surface texture of prepared dentin and may alter the retention of fixed restorations. Aims: The aim was to evaluate the effect of dentin desensitizers on the retention of complete cast metal crowns luted with glass ionomer cement. Subjects and Methods: Fifty freshly extracted human premolars were subjected to standardized tooth preparation (20° total convergence, 4 mm axial height with a computer numerically controlled machine. Individual cast metal crowns were fabricated from a base metal alloy. Dentin desensitizers included none (control, a glutaraldehyde (GLU based primer (Gluma desensitizer, casein phosphopeptide (CPP-amorphous calcium phosphate (ACP (GC Mousse, erbium, chromium: YSGG laser (Waterlase MD Turbo, Biolase and Pro-Argin (Colgate Sensitive Pro-Relief desensitizing polishing paste. After desensitization, crowns were luted with glass ionomer cement and kept for 48 h at 37°C in 100% relative humidity. The samples were tested using a universal testing machine by applying a load at a crosshead speed of 0.5 mm/min. Statistical Analysis Used: Statistical analysis included One-way ANOVA, followed by the Scheffe post-hoc test with P < 0.05. Results: All dentin desensitizers showed significantly different values: Pro-Argin (4.10 Megapascals [Mpa] < CPP-ACP (4.01 mpa < GLU based primer (3.87 Mpa < Virgin dentin (3.65 Mpa < LASER (3.37 Mpa. Conclusions : On comparing the effect of prepared virgin dentin, GLU based primer, CPP-ACP, LASER and Pro-Argin on the retention of complete cast metal crowns luted with glass ionomer cement on prepared teeth, it can be concluded that Pro-Argin and CPP-ACP showed the best retention in this in vitro study.

Doxycycline desensitization in chronic Q fever—A critical tool for the clinician

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Aila Luise Caplunik-Pratsch

2018-01-01

Full Text Available We present the case of a 45 year old woman with acute Q fever pneumonia who progressed to the chronic phase of the disease despite azithromycin therapy. A trial of doxycycline was halted because of severe allergy and she was put on clarithromycin and later moxifloxacin. Failure of both drugs required desensitization to doxycycline with escalating doses. After two-year treatment with doxycycline-hydroxychloroquine combination, complete recovery was declared. Our case highlights the option of doxycycline desensitization when an acute allergic reaction poses an obstacle to optimal treatment.

Rapid desensitization induces internalization of antigen-specific IgE on mouse mast cells.

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Oka, Tatsuya; Rios, Eon J; Tsai, Mindy; Kalesnikoff, Janet; Galli, Stephen J

2013-10-01

Rapid desensitization transiently prevents severe allergic reactions, allowing administration of life-saving therapies in previously sensitized patients. However, the mechanisms underlying successful rapid desensitization are not fully understood. We sought to investigate whether the mast cell (MC) is an important target of rapid desensitization in mice sensitized to exhibit IgE-dependent passive systemic anaphylaxis in vivo and to investigate the antigen specificity and underlying mechanisms of rapid desensitization in our mouse model. C57BL/6 mice (in vivo) or primary isolated C57BL/6 mouse peritoneal mast cells (PMCs; in vitro) were passively sensitized with antigen-specific anti-2,4-dinitrophenyl IgE, anti-ovalbumin IgE, or both. MCs were exposed over a short period of time to increasing amounts of antigen (2,4-dinitrophenyl-human serum albumin or ovalbumin) in the presence of extracellular calcium in vitro or by means of intravenous administration to sensitized mice in vivo before challenging the mice with or exposing the PMCs to optimal amounts of specific or irrelevant antigen. Rapidly exposing mice or PMCs to progressively increasing amounts of specific antigen inhibited the development of antigen-induced hypothermia in sensitized mice in vivo and inhibited antigen-induced PMC degranulation and prostaglandin D2 synthesis in vitro. Such MC hyporesponsiveness was induced antigen-specifically and was associated with a significant reduction in antigen-specific IgE levels on MC surfaces. Rapidly exposing MCs to progressively increasing amounts of antigen can both enhance the internalization of antigen-specific IgE on the MC surface and also desensitize these cells in an antigen-specific manner in vivo and in vitro. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Frequency and severity of reactions to a 325-mg aspirin dose during desensitization.

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Schuler, Charles F; Baldwin, James L; Baptist, Alan P

2017-03-01

The frequency with which patients with aspirin-exacerbated respiratory disease (AERD) react to 325 mg of aspirin during aspirin desensitization, or fail to react at all, is not fully known. To determine the rate and type of reaction at 325 mg of aspirin during desensitization. A retrospective study of 104 patients who underwent aspirin desensitization from 2010 to 2016 was performed. A standard desensitization protocol (starting at 20-40 mg, progressing through 325 mg, and extinguishing reactions by dose repetition) was used. Reactions were defined by upper respiratory tract symptoms, lower respiratory tract symptoms, and/or forced expiratory volume in 1 second decrease of 15% or greater. Patients who did and did not react were compared by logistic regression. Eighty-four patients reacted (81%) and 20 did not (19%). Seventy-seven patients who had a provoking reaction at 162 mg of aspirin or less subsequently extinguished their reactions before they reached a dose of 325 mg and had no problems at that dose; one subsequent 325-mg reaction occurred during a protocol violation. One initial provoking reaction to 325 mg occurred. Both 325-mg reactions were mild, and neither met the forced expiratory volume in 1 second criterion for a clinically meaningful change. The remaining 5 patients could not complete the protocol because of persistent reactions or social reasons. Reactors were more likely to have had asthma for more than 10 years than nonreactors (odds ratio, 3.2; 95% confidence interval, 1.0-10.3; P = .05). During aspirin desensitization for AERD, provoking reactions at the 325-mg dose are rare (1%) and mild. Patients who react at 162 mg or less and extinguish their reactions may be able to administer the 325-mg dose at home. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Analysis of the cytotoxicity of carbon-based nanoparticles, diamond and graphite, in human glioblastoma and hepatoma cell lines

DEFF Research Database (Denmark)

Zakrzewska, Karolina Ewa; Samluk, Anna; Wierzbicki, Mateusz

2015-01-01

carbon based nanoparticles, diamond and graphite, on glioblastoma and hepatoma cells were compared. First, we confirmed previous results that diamond nanoparticles are practically nontoxic. Second, graphite nanoparticles exhibited a negative impact on glioblastoma, but not on hepatoma cells. The studied...... carbon nanoparticles could be a potentially useful tool for therapeutics delivery to the brain tissue with minimal side effects on the hepatocytes. Furthermore, we showed the influence of the nanoparticles on the stable, fluorescently labeled tumor cell lines and concluded that the labeled cells...

Hydrogen sulfide (H2S)/cystathionine γ-lyase (CSE) pathway contributes to the proliferation of hepatoma cells

International Nuclear Information System (INIS)

Pan, Yan; Ye, Shuang; Yuan, Dexiao; Zhang, Jianghong; Bai, Yang; Shao, Chunlin

2014-01-01

Highlights: • Inhibition of H 2 S/CSE pathway strongly stimulates cellular apoptosis. • Inhibition of H 2 S/CSE pathway suppresses cell growth by blocking EGFR pathway. • H 2 S/CSE pathway is critical for maintaining the proliferation of hepatoma cells. - Abstract: Hydrogen sulfide (H 2 S)/cystathionine γ-lyase (CSE) pathway has been demonstrated to play vital roles in physiology and pathophysiology. However, its role in tumor cell proliferation remains largely unclear. Here we found that CSE over-expressed in hepatoma HepG2 and PLC/PRF/5 cells. Inhibition of endogenous H 2 S/CSE pathway drastically decreased the proliferation of HepG2 and PLC/PRF/5 cells, and it also enhanced ROS production and mitochondrial disruption, pronounced DNA damage and increased apoptosis. Moreover, this increase of apoptosis was associated with the activation of p53 and p21 accompanied by a decreased ratio of Bcl-2/Bax and up-regulation of phosphorylated c-Jun N-terminal kinase (JNK) and caspase-3 activity. In addition, the negative regulation of cell proliferation by inhibition of H 2 S/CSE system correlated with the blockage of cell mitogenic and survival signal transduction of epidermal growth factor receptor (EGFR) via down-regulating the extracellular-signal-regulated kinase 1/2 (ERK1/2) activation. These results demonstrate that H 2 S/CSE and its downstream pathway contribute to the proliferation of hepatoma cells, and inhibition of this pathway strongly suppress the excessive growth of hepatoma cells by stimulating mitochondrial apoptosis and suppressing cell growth signal transduction

Sensory Desensitization Training for Successful Net Application and EEG/ERP Acquisition in Difficult to Test Children

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Roesler, Cynthia P.; Flax, Judy; MacRoy-Higgins, Michelle; Fermano, Zena; Morgan-Byrne, Julie; Benasich, April A.

2013-01-01

This study examined the effectiveness of sensory desensitization training for 12 nonverbal children with autism to facilitate participation in an electrophysiological study assessing linguistic processing. Sensory desensitization was achieved for 10 of the 12 children and thus allowed collection of usable data in a passive linguistic paradigm.…

Effects Of Desensitization Treatment On Core-Condition Training

Science.gov (United States)

Fry, P. S.

1973-01-01

Pre- and posttest ratings on measures of helping skills such as empathy, respect, concreteness, and genuineness were obtained in the preliminary and advanced training. A significant training effect was obtained for both groups. Desensitization treatment was a significant source of variance for the experimental subjects in training. (Author/LA)

β-Adrenergic receptors desensitization is not involved in exercise-induced cardiac fatigue: NADPH oxidase-induced oxidative stress as a new trigger.

Science.gov (United States)

Vitiello, Damien; Boissière, Julien; Doucende, Grégory; Gayrard, Sandrine; Polge, Anne; Faure, Patrice; Goux, Aurélie; Tanguy, Stéphane; Obert, Philippe; Reboul, Cyril; Nottin, Stéphane

2011-11-01

Prolonged strenuous exercise (PSE) induces transient left ventricular (LV) dysfunction. Previous studies suggest that β-adrenergic pathway desensitization could be involved in this phenomenon, but it remains to be confirmed. Moreover, other underlying mechanisms involving oxidative stress have been recently proposed. The present study aimed to evaluate the involvement of both the β-adrenergic pathway and NADPH oxidase (Nox) enzyme-induced oxidative stress in myocardial dysfunction in rats following PSE. Rats were divided into 4 groups: controls (Ctrl), 4-h exercised on treadmill (PSE), and 2 groups in which Nox enzyme was inhibited with apocynin treatment (Ctrl APO and PSE APO, respectively). We evaluated cardiac function in vivo and ex vivo during basal conditions and isoproterenol stress. GSH/GSSG ratio, cardiac troponin I (cTnI) release, and lipid peroxidation (MDA) were evaluated. PSE induced a decrease in LV developed pressure, intrinsic myocardial contractility, and relaxation associated with an increase in plasma cTnI release. Our in vivo and ex vivo results demonstrated no differences in myocardial response to isoproterenol and of effective dose 50 between control and PSE rats. Interestingly, the LV dysfunction was reversed by apocynin treatment. Moreover, apocynin prevented cellular oxidation [GSH/GSSG ratio: PSE APO rats vs. PSE rats in arbitrary units (au): 1.98 ± 0.07 vs. 1.35 ± 0.10; P stress from the Nox enzyme.

Hepatitis B virus X protein mutant HBxΔ127 promotes proliferation of hepatoma cells through up-regulating miR-215 targeting PTPRT

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Liu, Fabao [Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071 (China); Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China); You, Xiaona [Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071 (China); Chi, Xiumei [Department of Hepatology, The First Hospital, Jilin University, Changchun 130021 (China); Wang, Tao [Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071 (China); Ye, Lihong [Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China); Niu, Junqi, E-mail: junqiniu@yahoo.com.cn [Department of Hepatology, The First Hospital, Jilin University, Changchun 130021 (China); Zhang, Xiaodong, E-mail: zhangxd@nankai.edu.cn [Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071 (China)

2014-02-07

Highlights: • Relative to wild type HBx, HBX mutant HBxΔ127 strongly enhances cell proliferation. • Relative to wild type HBx, HBxΔ127 remarkably up-regulates miR-215 in hepatoma cells. • HBxΔ127-elevated miR-215 promotes cell proliferation via targeting PTPRT mRNA. - Abstract: The mutant of virus is a frequent event. Hepatitis B virus X protein (HBx) plays a vital role in the development of hepatocellular carcinoma (HCC). Therefore, the identification of potent mutant of HBx in hepatocarcinogenesis is significant. Previously, we identified a natural mutant of the HBx gene (termed HBxΔ127). Relative to wild type HBx, HBxΔ127 strongly enhanced cell proliferation and migration in HCC. In this study, we aim to explore the mechanism of HBxΔ127 in promotion of proliferation of hepatoma cells. Our data showed that both wild type HBx and HBxΔ127 could increase the expression of miR-215 in hepatoma HepG2 and H7402 cells. However, HBxΔ127 was able to significantly increase miR-215 expression relative to wild type HBx in the cells. We identified that protein tyrosine phosphatase, receptor type T (PTPRT) was one of the target genes of miR-215 through targeting 3′UTR of PTPRT mRNA. In function, miR-215 was able to promote the proliferation of hepatoma cells. Meanwhile anti-miR-215 could partially abolish the enhancement of cell proliferation mediated by HBxΔ127 in vitro. Knockdown of PTPRT by siRNA could distinctly suppress the decrease of cell proliferation mediated by anti-miR-215 in HepG2-XΔ127/H7402-XΔ127 cells. Moreover, we found that anti-miR-215 remarkably inhibited the tumor growth of hepatoma cells in nude mice. Collectively, relative to wild type HBx, HBxΔ127 strongly enhances proliferation of hepatoma cells through up-regulating miR-215 targeting PTPRT. Our finding provides new insights into the mechanism of HBx mutant HBxΔ127 in promotion of proliferation of hepatoma cells.

Fibronectin synthesized by a human hepatoma cell line

International Nuclear Information System (INIS)

Glasgow, J.E.; Colman, R.W.

1984-01-01

Fibronectin is a family of immunologically similar glycoproteins which mediate a variety of cell-cell and cell-substratum interactions. It is a constituent of the extracellular matrix of connective tissue and circulates in plasma. When suspension and adherent cultures of a human hepatoma cell line (SK-HEP-1) were incubated in serum-free medium, the resulting conditioned medium contained material which was specifically immunoprecipitated by antisera to human plasma fibronectin. By double immunodiffusion, a component in the conditioned culture medium was shown to form a line of identity with fibronectin in human plasma and to migrate as an alpha 2- to beta-globulin during immunoelectrophoresis. Human fibronectin was quantified in conditioned medium by electroimmunodiffusion, and was found to increase for at least three days at about 0.1 micrograms/10(6) cells/day. Adherent cultures of SK-HEP-1 cells were incubated with L-[ 35 S]methionine to label newly synthesized proteins. Labeled fibronectin in conditioned medium or in cell extracts comigrated with fibronectin in human plasma as shown by autoradiography following crossed-immunoelectrophoresis. Fibronectin was demonstrated in the extra-cellular matrix of adherent SK-HEP-1 cultures by immunofluorescence. It was shown previously that SK-HEP-1 cells synthesize alpha 1-protease inhibitor, one of the products of normal hepatocytes. The finding that these hepatoma cells also synthesize fibronectin supports the concept that the hepatocyte may be one source of circulating fibronectin, a possibility consistent with the established role of this cell type in blood plasma protein synthesis

Effects of agonist efficacy on desensitization of phosphoinositide hydrolysis mediated by m1 and m3 muscarinic receptors expressed in Chinese hamster ovary cells

International Nuclear Information System (INIS)

Hu, J.; Wang, S.Z.; el-Fakahany, E.E.

1991-01-01

Muscarinic receptor agonist-induced desensitization of phosphoinositide (PI) hydrolysis and loss of receptors were studied in Chinese hamster ovary (CHO) cells transfected with the m1 and m3 muscarinic receptor genes. Long-term exposure to the full agonist carbamylcholine (CBC) resulted in a time-dependent attenuation of the maximal PI response and a decrease in agonist potency. This desensitization was accompanied by a parallel loss of maximal ligand binding without an alteration of the binding affinity. The time course of both receptor desensitization and down-regulation was similar in m1 and m3 CHO cells. The PI response to the partial agonist McN-A-343 (McN) in m1 cells was more sensitive to desensitization by CBC than the response to the latter agonist, and this desensitization was faster than receptor down-regulation. Desensitization of the PI response to McN was reflected as a decrease in the maximal response without a marked change in potency. McN induced slow desensitization of the PI response to CBC but a much faster desensitization of its own response. Our data provide evidence that although muscarinic agonist-induced desensitization of PI hydrolysis in CHO cells is due mainly to loss of receptors, there are other important factors which play a role in this process, e.g., receptor-effector uncoupling. The relative contribution of these different mechanisms depends on the efficacy of the agonists used for the receptor desensitization and activation steps

The Process of Fear Reduction Through Systematic Desensitization

Science.gov (United States)

Schroeder, Harold E.; Rich, Alex R.

1976-01-01

This study investigated the process of fear change during a course of systematic desensitization therapy. Behavioral, subjective, and physiological measures of fear were taken following each of eight therapy sessions. Changes in one fear system did not appear to be primary in initiating changes in the other fear systems. (Author)

Effects of a Dicalcium and Tetracalcium Phosphate-Based Desensitizer on In Vitro Dentin Permeability.

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Jianfeng Zhou

Full Text Available The present study evaluated the effectiveness of a dicalcium and tetracalcium phosphate-based desensitizer in reducing dentin permeability in vitro. Dentin fluid flow was measured before and after treatment of dentin with patent dentinal tubules using 1 or 3 applications of the dicalcium and tetracalcium phosphate containing agent TeethmateTM (TM and comparing the results with two sodium fluoride varnishes VellaTM (VLA and VanishTM (VAN, after storage in artificial saliva for 24 h, 48 h and 7 days. Significant differences were observed among the 4 methods employed for reducing dentin permeability (p < 0.001 and the 3 post-treatment times (p < 0.001. VLA and VAN never achieved 50% permeability reductions consistently in any of the 3 time periods. Only the calcium phosphate-based desensitizer applied for 3 times consistently reduced dentin permeability by 50% after 24 h. When applied once, the permeability reduction of TM increased progressively over the 3 time periods. After 7 days, only one and three applications of the calcium phosphate-based desensitizer consistently reduced dentin permeability by more than 50%. Permeability reductions corresponded well with scanning electron microscopy examination of dentinal tubule orifice occlusion in dentin specimens treated with the agents. Overall, the dicalcium and tetracalcium phosphate-based desensitizer is effective in reducing dentin permeability via a tubule occlusion mechanism. The ability of the agent to reduce dentin permeability renders it to be potentially useful as a clinical dentin desensitizing agent, which has to be confirmed in future clinical studies. By contrast, the two sodium fluoride varnishes are not effective in dentin permeability reduction and should be considered as topical fluoride delivering agents rather than tubular orifice-blocking agents.

Influence of bleaching and desensitizing gel on bond strength of orthodontic brackets

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Fernanda Alves Rodrigues Britto

2015-04-01

Full Text Available OBJECTIVE: The objective of this study was to assess, in vitro, the influence of bleaching gel and the use of desensitizing agent over bond strength of ceramic brackets bonded to bovine enamel. METHODS: One hundred bovine incisors were selected and randomly divided into five groups (n = 20: Group 1, control group (without bleaching; Group 2, bleached with 35% hydrogen peroxide; Group 3, bleached with 35% hydrogen peroxide (three applications, 15 minutes each and desensitizing agent applied for 10 minutes; Group 4, bleached with 35% hydrogen peroxide for 40 minutes; Group 5, bleached with 35% hydrogen peroxide for 40 minutes with desensitizing agent applied for 10 minutes. Brackets were bonded 7 days after bleaching and submitted to shear bond strength test after 24 hours at a compression rate of 1 mm/minute. After fracture, the adhesive remnant index (ARI was assessed under stereoscopic at 40 x magnification. Shear strength data (MPa were submitted to one-way ANOVA and Tukey's test with significance level set at 5%. RESULTS: Group 5 (29.33 MPa showed significantly higher bond strength than Group 1 (19.19 MPa, Group 2 (20.59 MPa and Group 4 (23.25 MPa, but with no difference in comparison to Group 3. There was no significant difference among the other groups. The adhesive remnant index showed predominance of score 3, that is, all resin remained adhered to enamel for all groups. CONCLUSION: Bleaching with 35% hydrogen peroxide with calcium associated with desensitizing agent application produced higher bond strength values of brackets bonded to bovine enamel.

Distinct structural features of cyclothiazide are responsible for effects on peak current amplitude and desensitization kinetics at iGluR2

DEFF Research Database (Denmark)

Hald, Helle; Ahring, Philip Kiær; Timmermann, Daniel Brunicardi

2009-01-01

Ionotropic glutamate receptors (iGluRs) mediate fast excitatory neurotransmission. Upon glutamate application, 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid receptors undergo rapid and almost complete desensitization that can be attenuated by positive allosteric modulators. The molecu......Ionotropic glutamate receptors (iGluRs) mediate fast excitatory neurotransmission. Upon glutamate application, 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid receptors undergo rapid and almost complete desensitization that can be attenuated by positive allosteric modulators......) in micromolar: 10 (CTZ), 26 (NS1493), 43 (NS5206), and 48 (NS5217)]. The four modulators divide into three groups according to efficacy and desensitization kinetics: (1) CTZ increases the peak current efficacy twice as much as the three analogues and nearly completely blocks receptor desensitization; (2) NS5206...... and NS5217 have low efficacy and only attenuate desensitization partially; (3) NS1493 has low efficacy but nearly completely blocks receptor desensitization. A hydrophobic substituent at the 3-position of the 1,1-dioxo-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine ring system is important for compound...

Comparison of Cue-Controlled Desensitization, Rational Restructuring, and a Credible Placebo in the Treatment of Speech Anxiety.

Science.gov (United States)

Lent, Robert W.; And Others

1981-01-01

The efficacy of cue-controlled desensitization and systematic rational restructuring was compared with a placebo method and a waiting-list control in reducing public speaking and nontargeted anxieties. Cue-controlled desensitization was generally more effective than the other groups in reducing subjective speech anxiety. (Author)

Cell surface GRP78 facilitates hepatoma cells proliferation and migration by activating IGF-IR.

Science.gov (United States)

Yin, Yancun; Chen, Chen; Chen, Jinliang; Zhan, Renhui; Zhang, Qiang; Xu, Xiaoyan; Li, Defang; Li, Minjing

2017-07-01

The 78kDa glucose regulated protein (GRP78) is a multifunctional chaperone that is involved in a variety of cellular processes. Insulin like growth factor I receptor (IGF-IR) often aberrant expresses in many types of tumor cells. The IGF-IR signaling plays key roles in carcinogenesis and maintenance of the malignant phenotype. The crosstalk between GRP78 and IGF-IR molecules has not well been illuminated. Here, we demonstrated a reciprocal regulation of GRP78 expression and IGF-IR pathway activation. IGF-I induced GRP78 expression in hepatoma cells. IGF-IR knockdown or IGF-IR inhibitor repressed GRP78 expression. Both phosphatidylinositol 3-kianase (PI3K) and mitogen-activated protein kinase (MAPK) pathways involved in IGF-I induction of GRP78 expression. Interestingly, treatment of hepatoma cells with IGF-I re-distributes GRP78 from endoplasmic reticulum (ER) to cell surface and promotes its physical interaction with IGF-IR. Also, GRP78 promotes IGF-IR phosphorylation and activation. Blocked of GRP78 by small interfering RNA or inhibition of GRP78 function by (-)-epigallocatechin gallate (EGCG) blocks IGF-I induced IGF-IR phosphorylation and its downstream signaling. Further, blocked cell surface GRP78 with antibody inhibits IGF-I stimulated cellular proliferation and migration. These data reveal an essential role for the molecular chaperone GRP78 in IGF-IR signaling and implicate the use of GRP78 inhibitors in blocking IGF-IR signaling in hepatoma cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

Science.gov (United States)

Chen, T S; Ottenweller, J; Luke, A; Santos, S; Keeting, P; Cuy, R; Lea, M A

1989-01-01

A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut allergic patients

Science.gov (United States)

Schneider, Lynda C.; Rachid, Rima; LeBovidge, Jennifer; Blood, Emily; Mittal, Mudita; Umetsu, Dale T.

2015-01-01

Background Peanut allergy is a major public health problem that affects 1% of the population and has no effective therapy. Objective To examine the safety and efficacy of oraldesensitization in peanut allergic children in combination with a brief course of anti-IgE monoclonal antibody (omalizumab, Xolair). Methods We performed oral peanut desensitization in peanut allergic children at high risk for developing significant peanut-induced allergic reactions. Omalizumab was administered prior to and during oral peanut desensitization. Results We enrolled 13 children (median age, 10 years), with a median peanut-specific IgE of 229 kUA/L and a median total serum IgE of 621 kU/L, who failed an initial double-blind placebo controlled food challenge at doses 100 mg peanut flour. After pre-treatment with omalizumab, all subjects tolerated the initial 11 desensitization doses given on the first day, including the maximum dose of 500 mg peanut flour (cumulative dose, 992 mg, equivalent to >2 peanuts), requiring minimal or no rescue therapy. 12 subjects then reached the maximum maintenance dose of 4,000 mg peanut flour/day in a median time of 8 weeks, at which point omalizumab was discontinued. All 12 subjects continued on 4,000 mg peanut flour/day and subsequently tolerated a challenge with 8,000 mg peanut flour (equivalent to about 20 peanuts), or 160 to 400 times the dose tolerated before desensitization. During the study, 6 of the 13 subjects experienced mild or no allergic reactions; 6 subjects had Grade 2, and 2 subjects Grade 3 reactions, all of which responded rapidly to treatment. Conclusions Among children with high-risk peanut allergy, treatment with omalizumab may facilitate rapid oral desensitization, and qualitativelyimprove the desensitization process. PMID:24176117

Drug Transporter Expression and Activity in Human Hepatoma HuH-7 Cells

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Elodie Jouan

2016-12-01

Full Text Available Human hepatoma cells may represent a valuable alternative to the use of human hepatocytes for studying hepatic drug transporters, which is now a regulatory issue during drug development. In the present work, we have characterized hepatic drug transporter expression, activity and regulation in human hepatoma HuH-7 cells, in order to determine the potential relevance of these cells for drug transport assays. HuH-7 cells displayed notable multidrug resistance-associated protein (MRP activity, presumed to reflect expression of various hepatic MRPs, including MRP2. By contrast, they failed to display functional activities of the uptake transporters sodium taurocholate co-transporting polypeptide (NTCP, organic anion-transporting polypeptides (OATPs and organic cation transporter 1 (OCT1, and of the canalicular transporters P-glycoprotein and breast cancer resistance protein (BCRP. Concomitantly, mRNA expressions of various sinusoidal and canalicular hepatic drug transporters were not detected (NTCP, OATP1B1, organic anion transporter 2 (OAT2, OCT1 and bile salt export pump or were found to be lower (OATP1B3, OATP2B1, multidrug and toxin extrusion protein 1, BCRP and MRP3 in hepatoma HuH-7 cells than those found in human hepatocytes, whereas other transporters such as OAT7, MRP4 and MRP5 were up-regulated. HuH-7 cells additionally exhibited farnesoid X receptor (FXR- and nuclear factor erythroid 2-related factor 2 (Nrf2-related up-regulation of some transporters. Such data indicate that HuH-7 cells, although expressing rather poorly some main hepatic drug transporters, may be useful for investigating interactions of drugs with MRPs, notably MRP2, and for studying FXR- or Nrf2-mediated gene regulation.

Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab.

Science.gov (United States)

Lobashevsky, Andrew L; Higgins, Nancy G; Rosner, Kevin M; Mujtaba, Muhammad A; Goggins, William C; Taber, Tim E

2013-07-27

Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates. In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34%-99%), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti-human leukocyte antigen antibodies were analyzed before and after desensitization. Reduction of cPRA from 25% to 50% was noted for anti-class I (5 patients, within 20-60 days) and anti-class II (3 patients, within 10-20 days) antibodies. After initial reduction of cPRA, the cPRA increased within 120 days. In 24 patients, decrease in mean fluorescence intensity of antibodies by more than 50% was noted at follow-up, but there was no reduction of cPRA. Rebound occurred in 65% patients for anti-class I antibodies at 350 days and anti-class II antibodies at 101 to 200 days. Probability of rebound effect was higher in patients with mean fluorescence intensity of more than 10,700 before desensitization, anti-class II antibodies, and history of previous transplant. The desensitization protocol had limited efficacy in highly sensitized kidney transplant candidate because of the short period with antibody reduction and high frequency of rebound effect.

Effect of Apheresis for ABO and HLA Desensitization on Anti-Measles Antibody Titers in Renal Transplantation

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Ulf Schönermarck

2011-01-01

Full Text Available Desensitization strategies for ABO-incompatible renal transplants with plasma exchange (PE or specific immunoadsorption (IA decrease immunoglobulin levels. After recent measles outbreak and decreasing vaccination rates, we studied the impact of apheresis on anti-measles antibodies. Anti-measles antibodies were measured before desensitization, before transplantation and during followup in 12 patients with ABO incompatibility (2x PE only, 8x IA only, and 2x IA and PE and 3 patients with donor-specific HLA antibodies (all PE. Patients received rituximab, IVIG, and standard immunosuppressive therapy. All patients had detectable anti-measles antibodies before desensitization (mean 3238 mU/l, range 560–8100. After 3–6 PE sessions, titers decreased significantly to 1710 mU/l (<0.05, in one patient to nondetectable values, while IA only maintained protective titers. After a median followup of 64 days, anti-measles antibodies returned to baseline in all patients. Immunity against measles was temporarily reduced by apheresis but remained detectable in most patients at time of transplantation. Desensitization maintains long-term protective immunity against measles.

miR-150-5p inhibits hepatoma cell migration and invasion by targeting MMP14.

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Tao Li

Full Text Available Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related mortality worldwide. Despite progress in diagnostics and treatment of HCC, its prognosis remains poor because the molecular mechanisms underlying hepatocarcinogenesis are not well understood. In the study, we focused on identifying the role of miRNAs in HCC progression. miRNA microarray was used to analyze the differentially expressed miRNAs, and the results were validated by qPCR. We found that the miR-150-5p expression is down-regulated in HCC tissues compared with pair non-tumor tissues. miR-150-5p expression is also decreased in metastatic cancer tissues compared with pair primary tissues, indicating that miR-150-5p may be involved in HCC metastasis. Functionally, miR-150-5p inhibition significantly promotes hepatoma cell migration and invasion, whereas miR-150-5p overexpression suppresses cancer cell migration and invasion in vitro. The matrix metalloproteinase 14 (MMP14 is identified as a new target gene of miR-150-5p. miR-150-5p markedly inhibits MMP14 expression in hepatoma cells, and miR-150-5p expression is negative correlation with MMP14 expression in vivo. More important, re-expression of MMP14 in hepatoma cells partially reverses the effect of miR-150-5p in inhibiting cell invasion.

Comment on the Morris and Suckerman Study of Therapist Warmth as a Factor in Automated Systematic Desensitization

Science.gov (United States)

McGlynn, F. Dudley; And Others

1976-01-01

Criticism of the study relating effects of therapist warmth to desensitization include: the use of surrogate, student subjects; nonstandard desensitization procedures; and no control group. Morris and Suckerman respond that the first two criticisms rely on selective reading of the literature and the third is irrelevant. (NG)

Crystal structure and dynamics of a lipid-induced potential desensitized-state of a pentameric ligand-gated channel

Energy Technology Data Exchange (ETDEWEB)

Basak, Sandip [Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, United States; Schmandt, Nicolaus [Department of Neuroscience, School of Medicine, Case Western Reserve University, Cleveland, United States; Gicheru, Yvonne [Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, United States; Chakrapani, Sudha [Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, United States

2017-03-06

Desensitization in pentameric ligand-gated ion channels plays an important role in regulating neuronal excitability. Here, we show that docosahexaenoic acid (DHA), a key ω-3 polyunsaturated fatty acid in synaptic membranes, enhances the agonist-induced transition to the desensitized state in the prokaryotic channel GLIC. We determined a 3.25 Å crystal structure of the GLIC-DHA complex in a potentially desensitized conformation. The DHA molecule is bound at the channel-periphery near the M4 helix and exerts a long-range allosteric effect on the pore across domain-interfaces. In this previously unobserved conformation, the extracellular-half of the pore-lining M2 is splayed open, reminiscent of the open conformation, while the intracellular-half is constricted, leading to a loss of both water and permeant ions. These findings, in combination with spin-labeling/EPR spectroscopic measurements in reconstituted-membranes, provide novel mechanistic details of desensitization in pentameric channels.

Preparation of a radioactive boron compound (B-I-131-lipiodol) for neutron capture therapy of hepatoma

International Nuclear Information System (INIS)

Chou, F.I.; Chung, H.P.; Chung, R.J.; Wen, H.W.; Wei, Y.Y.; Kai, J.J.; Lui, W.Y.; Chi, C.W.

2000-01-01

In our research, a radioactive boron compound, B-I-131-lipiodol, that can be selectively retained in hepatoma cells was prepared. Combining the effect of α particles produced by boron neutron capture reaction with the β particles released by radionuclides in the radioactive boron compounds will produce a synergistic killing effect on cancer cells. Human hepatoma HepG2 cell cultures were used to examine the stability and the intracellular distribution of the radioactive boron drug. Microscopes were used to examine the interaction and retention of B-I-131-lipiodol globules in the individual hepatoma cell. Moreover, ICP-AES and NaI scintillation counter were performed to determine boron concentrations and I-131 radioactivity, respectively. Results showed that B-I-131-lipiodol with a boron concentration and a specific radioactivity ranged from 500-2000 ppm and 0.05-10 mCi/mL respectively was stably retained in serum. The radiochemical purity of B-I-131-lipiodol was 98%. After supplement with a medium containing B-I-131-lipiodol, the HepG2 cells had intracellular B-I-131-lipiodol globules in the cytoplasm as seen by inverted light microscope, the I-131 and boron can be stably retained in HepG2 cells. (author)

Applications of Desensitization Procedures for School-Related Problems; A Review.

Science.gov (United States)

Prout, H. Thompson; Harvey, John R.

1978-01-01

A variety of desensitization and counterconditioning procedures have been utilized to deal with school-related problems. These procedures are reviewed with respect to applications for treating school phobia, test anxiety, and other academic anxieties. (Author)

Crotalphine desensitizes TRPA1 ion channels to alleviate inflammatory hyperalgesia

Czech Academy of Sciences Publication Activity Database

Bressan, E.; Touška, Filip; Vetter, I.; Kistner, K.; Kichko, T. I.; Teixeira, N. B.; Picolo, G.; Cury, Y.; Lewis, R. J.; Fischer, M. J. M.; Zimmermann, K.; Reeh, P. W.

2016-01-01

Roč. 157, č. 11 (2016), s. 2504-2516 ISSN 0304-3959 Institutional support: RVO:67985823 Keywords : Crotalphine * desensitization * TRPA1 * CGRP * Ciguatoxin * Bradykinin * Zymosan Subject RIV: ED - Physiology Impact factor: 5.445, year: 2016

Parental desensitization to violence and sex in movies

NARCIS (Netherlands)

Romer, D.; Jamieson, P.E.; Bushman, B.J.; Bleakley, A.; Wang, A.; Langleben, D.; Jamieson, K.H.

2014-01-01

OBJECTIVES: To assess desensitization in parents' repeated exposure to violence and sex in movies. METHODS: A national US sample of 1000 parents living with at least 1 target child in 1 of 3 age groups (6 to 17 years old) viewed a random sequence of 3 pairs of short scenes with either violent or

Desensitization by progressive up-titration prevents first-dose effects on the heart: guinea pig study with ponesimod, a selective S1P1 receptor modulator.

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Markus Rey

Full Text Available Ponesimod, a selective S1P1 receptor modulator, reduces the blood lymphocyte count in all tested species by preventing egress of T and B cells from thymus and peripheral lymphoid organs. In addition, ponesimod transiently affects heart rate and atrioventricular (AV conduction in humans, effects not observed in mice, rats, and dogs with selective S1P1 receptor modulators, suggesting that the regulation of heart rate and rhythm is species dependent. In the present study, we used conscious guinea pigs implanted with a telemetry device to investigate the effects of single and multiple oral doses of ponesimod on ECG variables, heart rate, and blood pressure. Oral administration of ponesimod did not affect the sinus rate (P rate but dose-dependently induced AV block type I to III. A single oral dose of 0.1 mg/kg had no effect on ECG variables, while a dose of 3 mg/kg induced AV block type III in all treated guinea pigs. Repeated oral dosing of 1 or 3 mg/kg ponesimod resulted in rapid desensitization, so that the second dose had no or a clearly reduced effect on ECG variables as compared with the first dose. Resensitization of the S1P1 receptor in the heart was concentration dependent. After desensitization had been induced by the first dose of ponesimod, the cardiac system remained desensitized as long as the plasma concentration was ≥75 ng/ml. By using a progressive up-titration regimen, the first-dose effect of ponesimod on heart rate and AV conduction was significantly reduced due to desensitization of the S1P1 receptor. In summary, conscious guinea pigs implanted with a telemetry device represent a useful model to study first-dose effects of S1P1 receptor modulators on heart rate and rhythm. This knowledge was translated to a dosing regimen of ponesimod to be tested in humans to avoid or significantly reduce the first-dose effects.

The diagnostic application of Ga-67 scintigraphy in primary lung cancer, hepatoma and abdominal abscess

International Nuclear Information System (INIS)

Oshiumi, Yoshihiko

1983-01-01

It is difficult to detect tumor lesions by 67 Gascintigraphy, though it is named as a tumor scintigraphy. Recently, 67 Ga-scintigraphy is well used in the detection of inflammatic lesions. This paper is to discuss the detectability of lesions and diagnostic limitation on operability by 67 Ga-scintigraphy to primary lung cancer, minute hepatoma and abdominal absccess. Primary lung cancer: In detecting metastatic hilar lymph nodes, the sensitivity is 54%, and the specificity is 78%. In detecting metastatic mediastinal lymph nodes, the sensitivity is 32% and the specificity is 89%. Minute hepatoma : The detectability depended on the size of the lesion. It is hard to detect lesions with under 2 cm by 67 Ga-scintigraphy. Abdominal abscess : The sensitivity is 88%, and the specificity is 92%. (author)

Contribution of Pretesting to Several Measures of Semantic Desensitization Effectiveness

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Israel, Allen C.; And Others

1977-01-01

Snake- or spider-phobic subjects (N=32) were randomly assigned to one of four groups. Subjects receiving semantic desensitization therapy showed less posttest anxiety on the semantic differential than control subjects regardless of testing condition. (Author)

Micro-shear bond strength of resin cement to dentin after application of desensitizing toothpastes.

Science.gov (United States)

Bavbek, Andac Barkin; Goktas, Baris; Cekic-Nagas, Isil; Egilmez, Ferhan; Ergun, Gulfem; Eskitascioglu, Gurcan

2013-01-01

The aim of the study was to evaluate the effect of three desensitizing toothpastes on bonding of resin cements to dentin. The occlusal surfaces of 72 maxillary third molars were ground to obtain flat dentin surfaces and then divided into three groups according to three desensitizing toothpastes used: Sensodyne Rapid Relief (GlaxoSmithKline, SmithKline Beecham Ltd., Slough, UK), Signal Sensitive Expert (Unilever Sanayi ve Ticaret Türk A.Ş., Ümraniye, İstanbul, Turkey) and Colgate Sensitive Pro-Relief (Colgate Palmolive, New York, NY). Following bonding of the resin cement (Clearfil™ SA Cement, Kuraray Co, Osaka, Japan) to dentin, the specimens were light cured for 40 s with a LED (Elipar S10, 3M Espe, St. Paul, MN). The strength measurements were accomplished with a micro-shear testing machine (Bisco, Schaumburg, IL) at a cross-head speed of 0.5 mm/min until the failure occurs. Failure modes were examined using a stereomicroscope and scanning electron microscope. The data were analyzed with one-way analysis of variance (ANOVA) and Tukey HSD test (α = 0.05). ANOVA revealed that the application of desensitizing toothpastes had significant effects on bond strength of the resin cement tested to dentin (p < 0.05). Mixed failures were observed in all of the groups. The use of a desensitizing toothpaste before cementation might alter the bond strength of adhesively luted restorations.

Channel opening of gamma-aminobutyric acid receptor from rat brain: molecular mechanisms of the receptor responses.

Science.gov (United States)

Cash, D J; Subbarao, K

1987-12-01

The function of gamma-aminobutyric acid (GABA) receptors, which mediate transmembrane chloride flux, can be studied by use of 36Cl- isotope tracer with membrane from mammalian brain by quench-flow technique, with reaction times that allow resolution of the receptor desensitization rates from the ion flux rates. The rates of chloride exchange into the vesicles in the absence and presence of GABA were characterized with membrane from rat cerebral cortex. Unspecific 36Cl- influx was completed in three phases of ca. 3% (t 1/2 = 0.6 s), 56% (t 1/2 = 82 s), and 41% (t 1/2 = 23 min). GABA-mediated, specific chloride exchange occurred with 6.5% of the total vesicular internal volume. The GABA-dependent 36Cl- influx proceeded in two phases, each progressively slowed by desensitization. The measurements supported the presence of two distinguishable active GABA receptors on the same membrane mediating chloride exchange into the vesicles with initial first-order rate constants of 9.5 s-1 and 2.3 s-1 and desensitizing with first-order rate constants of 21 s-1 and 1.4 s-1, respectively, at saturation. The half-response concentrations were similar for both receptors, 150 microM and 114 microM GABA for desensitization and 105 microM and 82 microM for chloride exchange, for the faster and slower desensitizing receptors, respectively. The two receptors were present in the activity ratio of ca. 4/1, similar to the ratio of "low-affinity" to "high-affinity" GABA sites found in ligand binding experiments. The desensitization rates have a different dependence on GABA concentration than the channel-opening equilibria.(ABSTRACT TRUNCATED AT 250 WORDS)

Systematic Versus Semantic Desensitization and Implosive Therapy: A Comparative Study

Science.gov (United States)

Hekmat, Hamid

1973-01-01

In this study, both the semantic and systematic desensitization methods were found to be significantly more effective than the implosive therapy and the control treatments in the modification of phobic behavior among the college student population. (Author)

The effect of calcium phosphate-containing desensitizing agent on ...

African Journals Online (AJOL)

Objective: The aim of this study was to investigate the effect of calcium phosphate containing desensitizing pretreatments on the microtensile bond strength (MTBS) and microleakage of the multimode adhesive agent to dentin. Materials and Methods: In this study, twelve noncarious, freshly extracted human third molar teeth ...

Group Insight Versus Group Desensitization in Treating Speech Anxiety

Science.gov (United States)

Meichenbaum, Donald H.; And Others

1971-01-01

Results of this study indicated that the insight group was as effective as the desensitization group in significantly reducing speech anxiety over control group levels as assessed by behavioral, cognitive, and self-report measures given immediately after posttreatment and later at a three-month follow-up. (Author)

Effect of Systematic Desensitization on the Training of Counselors

Science.gov (United States)

Monke, Robert H.

1971-01-01

In determining whether the technique of desensitization would reduce the initial anxiety experienced by the beginning counselor trainee, analyses of the data revealed significantly less self-reported anxiety in the experimental group. No differences were found in heart rate, skin resistance, and tape-evaluation measures. (Author/CG(

Agonist mediated fetal muscle-type nicotinic acetylcholine receptor desensitization

Science.gov (United States)

The exposure of a developing embryo or fetus to teratogenic alkaloids from plants has the potential to cause developmental defects in livestock due to the inhibition of fetal movement by alkaloids. The mechanism behind the inhibition of fetal movement is the desensitization of fetal muscle-type nico...

Evaluating the impact of pre-transplant desensitization utilizing a plasmapheresis and low-dose intravenous immunoglobulin protocol on BK viremia in renal transplant recipients.

Science.gov (United States)

Gabardi, S; Townsend, K; Martin, S T; Chandraker, A

2013-08-01

A correlation exists between polyomavirus BK (BKV) viremia in renal transplant recipients (RTR) and the degree of immunosuppression. However, the impact of pre-transplant desensitization on the incidence of BKV viremia is unknown. This retrospective study evaluated living-donor RTR between January 2004 and December 2008 receiving routine BKV viral load monitoring. Patients were divided into those who underwent pre-transplant desensitization (n = 20) and those who did not (n = 71). The primary endpoint was the incidence of BKV viremia at 1 year post transplant. All demographic data were similar, except for more female patients (65% vs. 36.6%; P = 0.0392) in the desensitized group. More desensitized patients had a previous transplant (75% vs. 12.7%; P < 0.0001) and were more likely to be induced with basiliximab (75% vs. 35.2%; P = 0.0021). Following transplantation, antibody-mediated rejection (AMR) rates were highest in the desensitized group (55% vs. 1.4%; P < 0.0001). The incidence of BKV viremia at 1 year post transplant was significantly higher in desensitized patients (45% vs. 19.7%; P = 0.0385). Desensitization was also associated with a higher prevalence of BKV viremia at any time post transplant (50% vs. 22.5%; P = 0.0245), polyomavirus-associated nephropathy (20% vs. 2.8%; P = 0.0198) and BKV-related allograft loss (10% vs. 0%; P = 0.0464). Also of note, in a subgroup analysis of only our desensitized patients, it did not appear that development of AMR significantly impacted the incidence of BKV viremia in these individuals. This analysis reveals that pre-transplant desensitization significantly increases the risk for BKV viremia and nephropathy. © 2013 John Wiley & Sons A/S.

Replica of human dentin treated with different desensitizing agents: a methodological SEM study in vitro

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Pereira Jose Carlos

2002-01-01

Full Text Available This is a preliminary study to determine a methodological sequence in vitro which may allow the reproduction of dentin for SEM analysis, after the use of different desensitizing agents. Dentin discs obtained from extracted human third molars were etched with 6% citric acid, an artificial smear layer was created and the surface dentin discs were divided into four quadrants. Quadrants 2, 3 and 4 of each disc were conditioned with 6% citric acid. The desensitizing agents (Oxa-Gel®, Gluma Desensitizer and an experimental agent were applied to quadrants 3 and 4. To evaluate the acid resistance of the treatment, quadrant 4 was etched again with 6% citric acid. An impression was then taken with Aquasil ULV. After a setting period of 6 min, each disc was removed from the impression and stored in a moist-free environment for 24 h at 37ºC. After that time, a low-viscosity epoxy resin (Araltec GY 1109 BR was poured into the impression and cured for 24 h. All specimens were metal-coated for SEM analysis. Comparison of the photomicrographs of dentin discs with their respective impressions and resin replicas showed that this technique can reproduce the characteristics of the dentin surface treated with desensitizing agents.

GnRH signalling pathways and GnRH-induced homologous desensitization in a gonadotrope cell line (alphaT3-1).

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Poulin, B; Rich, N; Mas, J L; Kordon, C; Enjalbert, A; Drouva, S V

1998-07-25

Exposure of the gonadotrope cells to gonadotropin-releasing hormone (GnRH) reduces their responsiveness to a new GnRH stimulation (homologous desensitization). The time frame as well as the mechanisms underlying this phenomenon are yet unclear. We studied in a gonadotrope cell line (alphaT3-1) the effects of short as well as long term GnRH pretreatments on the GnRH-induced phospholipases-C (PLC), -A2 (PLA2) and -D (PLD) activities, by measuring the production of IP3, total inositol phosphates (IPs), arachidonic acid (AA) and phosphatidylethanol (PEt) respectively. We demonstrated that although rapid desensitization of GnRH-induced IP3 formation did not occur in these cells, persistent stimulation of cells with GnRH or its analogue resulted in a time-dependent attenuation of GnRH-elicited IPs formation. GnRH-induced IPs desensitization was potentiated after direct activation of PKC by the phorbol ester TPA, suggesting the involvement of distinct mechanisms in the uncoupling exerted by either GnRH or TPA on GnRH-stimulated PI hydrolysis. The levels of individual phosphoinositides remained unchanged under any desensitization condition applied. Interestingly, while the GnRH-induced PLA2 activity was rapidly desensitized (2.5 min) after GnRH pretreatments, the neuropeptide-evoked PLD activation was affected at later times, indicating an important time-dependent contribution of these enzymatic activities in the sequential events underlying the GnRH-induced homologous desensitization processes in the gonadotropes. Under GnRH desensitization conditions, TPA was still able to induce PLD activation and to further potentiate the GnRH-evoked PLD activity. AlphaT3-1 cells possess several PKC isoforms which, except PKCzeta, were differentially down-regulated by TPA (PKCalpha, betaII, delta, epsilon, eta) or GnRH (PKCbetaII, delta, epsilon, eta). In spite of the presence of PKC inhibitors or down-regulation of PKC isoforms by TPA, the desensitizing effect of the neuropeptide on

Delayed Cutaneous Hypersensitivity Reactions to Antibiotics: Management with Desensitization.

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McNulty, Caitlin M G; Park, Miguel A

2017-11-01

Successful desensitization to mild to moderate delayed cutaneous adverse reaction to antibiotics has been described in a limited number of antibiotics and found to be safe. However, there are ample opportunities to standardize protocols for delayed cutaneous adverse reactions to antibiotics. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of desensitizing products containing 8% arginine and calcium carbonate for hypersensitivity relief in MIH-affected molars: an 8-week clinical study.

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Bekes, Katrin; Heinzelmann, Karolin; Lettner, Stefan; Schaller, Hans-Günter

2017-09-01

The objective of this study was to compare the efficacy in reducing hypersensitivity in molar incisor hypomineralization (MIH)-affected molars immediately and over 8 weeks combining a single in-office application and a homed-based program with desensitizing products containing 8% arginine and calcium carbonate. Nineteen children with at least one MIH-affected molar with hypersensitivity were included. Hypersensitivity was assessed with an evaporative (air) stimulus and a tactile stimulus. Each child received a single in-office treatment with a desensitizing paste containing 8% arginine and calcium carbonate (elmex Sensitive Professional desensitizing paste), followed by 8 weeks of brushing twice daily with a desensitizing toothpaste containing 8% arginine, calcium carbonate with 1450 ppm fluoride (elmex Sensitive Professional toothpaste), using the elmex Sensitive Professional toothbrush. Additionally, the corresponding mouthwash (elmex Sensitive Professional mouthwash) was used. Clinical assessments were made at baseline, immediately after the in-office treatment and after 1, 2, 4 and 8 weeks of brushing twice daily. Fifty-six molars with an air blast hypersensitivity score of 2 or 3 (Schiff Cold Air Sensitivity Scale) were included. Application of the desensitizing paste decreased hypersensitivity significantly immediately and throughout the 8 weeks recalls (p MIH. This is the first study evaluating the desensitizing effect of a desensitizing paste containing 8% arginine and calcium carbonate in patients with MIH.

Influence of Contextual Cues on the Efficacy of Desensitization and a Credible Placebo in Alleviating Public Speaking Anxiety

Science.gov (United States)

Slutsky, Jeffrey M.; Allen, George J.

1978-01-01

After participating in a public speaking situation that allowed collection of self-report, physiological, and behavioral manifestations of anxiety, 67 subjects were randomly assigned to either desensitization, "T scope" therapy, or no treatment. Desensitization reduced public speaking anxiety in both contexts, whereas the placebo was effective…

Imaging Agonist-Induced D2/D3 Receptor Desensitization and Internalization In Vivo with PET/fMRI.

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Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian; Rosen, Bruce R; Mandeville, Joseph B

2016-04-01

This study investigated the dynamics of dopamine receptor desensitization and internalization, thereby proposing a new technique for non-invasive, in vivo measurements of receptor adaptations. The D2/D3 agonist quinpirole, which induces receptor internalization in vitro, was administered at graded doses in non-human primates while imaging with simultaneous positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). A pronounced temporal divergence between receptor occupancy and fMRI signal was observed: occupancy remained elevated while fMRI responded transiently. Analogous experiments with an antagonist (prochlorperazine) and a lower-affinity agonist (ropinirole) exhibited reduced temporal dissociation between occupancy and function, consistent with a mechanism of desensitization and internalization that depends upon drug efficacy and affinity. We postulated a model that incorporates internalization into a neurovascular-coupling relationship. This model yielded in vivo desensitization/internalization rates (0.2/min for quinpirole) consistent with published in vitro measurements. Overall, these results suggest that simultaneous PET/fMRI enables characterization of dynamic neuroreceptor adaptations in vivo, and may offer a first non-invasive method for assessing receptor desensitization and internalization.

Hydrogen sulfide (H{sub 2}S)/cystathionine γ-lyase (CSE) pathway contributes to the proliferation of hepatoma cells

Energy Technology Data Exchange (ETDEWEB)

Pan, Yan; Ye, Shuang; Yuan, Dexiao; Zhang, Jianghong; Bai, Yang; Shao, Chunlin, E-mail: clshao@shmu.edu.cn

2014-05-15

Highlights: • Inhibition of H{sub 2}S/CSE pathway strongly stimulates cellular apoptosis. • Inhibition of H{sub 2}S/CSE pathway suppresses cell growth by blocking EGFR pathway. • H{sub 2}S/CSE pathway is critical for maintaining the proliferation of hepatoma cells. - Abstract: Hydrogen sulfide (H{sub 2}S)/cystathionine γ-lyase (CSE) pathway has been demonstrated to play vital roles in physiology and pathophysiology. However, its role in tumor cell proliferation remains largely unclear. Here we found that CSE over-expressed in hepatoma HepG2 and PLC/PRF/5 cells. Inhibition of endogenous H{sub 2}S/CSE pathway drastically decreased the proliferation of HepG2 and PLC/PRF/5 cells, and it also enhanced ROS production and mitochondrial disruption, pronounced DNA damage and increased apoptosis. Moreover, this increase of apoptosis was associated with the activation of p53 and p21 accompanied by a decreased ratio of Bcl-2/Bax and up-regulation of phosphorylated c-Jun N-terminal kinase (JNK) and caspase-3 activity. In addition, the negative regulation of cell proliferation by inhibition of H{sub 2}S/CSE system correlated with the blockage of cell mitogenic and survival signal transduction of epidermal growth factor receptor (EGFR) via down-regulating the extracellular-signal-regulated kinase 1/2 (ERK1/2) activation. These results demonstrate that H{sub 2}S/CSE and its downstream pathway contribute to the proliferation of hepatoma cells, and inhibition of this pathway strongly suppress the excessive growth of hepatoma cells by stimulating mitochondrial apoptosis and suppressing cell growth signal transduction.

Efektivitas Desensitizing Agent dengan dan tanpa Fluor pada Metode in Office Bleaching terhadap Kandungan Mineral Gigi (Kajian In Vitro

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Yulita Kristanti

2015-12-01

Full Text Available In office bleaching menggunakan hidrogen peroksida 40% sering memberikan efek samping berupa linu baik selama maupun setelah perawatan tersebut dilakukan. Penelitian ini dilakukan dengan tujuan untuk mengetahui pengaruh waktu aplikasi dan kandungan fluor desensitizing agent pada metode in office bleaching terhadap kandungan mineral gigi. Delapan gigi masing-masing dipotong menjadi 4 bagian, 6 potong digunakan untuk pemeriksaan XRD awal. Gigi dikeringkan dalam oven suhu 50° selama 30 menit diserbuk, diambil 1 mg untuk diperiksa kandungan mineralnya dengan goniometer. Dua puluh empat potong yang lain dibagi dalam 4 kelompok perlakuan. Kelompok I: gigi diaplikasi bahan bleaching 0,5-1 mm hidrogen peroksida 40% selama 1 jam, dicuci, dikeringkan, diikuti aplikasi 0,1 ml desensitizing agent tanpa fluor (CPP-ACP selama 30 menit, dicuci, dikeringkan. Kelompok II : gigi diaplikasi CPP-ACP 30 menit, dicuci, dikeringkan, dibleaching menggunakan hidrogen peroksida 40% selama 1 jam. Selanjutnya gigi diaplikasi CPP-ACP 30 menit lagi, dicuci, dikeringkan. Kelompok III gigi dibleaching menggunakan hidrogen peroksida 40% selama 1 jam, dicuci, dikeringkan, diikuti aplikasi desensitizing agent yang mengandung fluor (CPP-ACFP selama 30 menit, dicuci, dikeringkan. Kelompok IV: gigi diaplikasi CPP-ACFP 30 menit, dicuci, dikeringkan, dibleaching menggunakan hidrogen peroksida 40% selama 1 jam. Selanjutnya gigi diaplikasi CPP-ACFP selama 30 menit, dicuci dikeringkan. Sesudah perlakuan, semua gigi dilakukan pemeriksaan kandungan mineral gigi dengan prosedur yang sama. Uji Mann Whitney menunjukkan penurunan mineral paling sedikit terjadi pada kelompok IV (4500. Desensitizing agent mengandung F sebelum dan sesudah perlakuan in office bleaching menunjukkan penurunan mineral paling kecil.   The Effectiveness of Desensitizing Agent with and without Fluorine in Office Bleaching Method to Tooth Mineral content. Tooth sensitivity arises during or after an in

Drug Hypersensitivity and Anaphylaxis in Cancer and Chronic Inflammatory Diseases: The Role of Desensitizations

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Mariana Castells

2017-11-01

Full Text Available Drug allergy is a rising problem in the twenty-first century which affects all populations and races, children, and adults, and for which the recognition, diagnosis, management, and treatment is still not well standardized. Classical and new chemotherapy drugs, monoclonal antibodies (MoAbs, and small molecules to treat cancer and chronic inflammatory diseases are aimed at improving quality of life and life expectancy of patients, but an increasing number of reactions including anaphylaxis precludes their use in targeted populations. Women are more affected by drug allergy and up to 27% of women with ovarian and breast cancer develop carboplatin allergy after multiple cycles of treatment. Carriers of BRCA genes develop drug allergy after fewer exposures and can present with severe reactions, including anaphylaxis. Atopic patients are at increased risk for chemotherapy and MoAbs drug allergy and the current patterns of treatment with recurrent and intermittent drug exposures may favor the development of drug allergies. To overcome drug allergy, desensitization has been developed, a novel approach which provides a unique opportunity to protect against anaphylaxis and to improve clinical outcomes. There is evidence that inhibitory mechanisms blocking IgE/antigen mast cell activation are active during desensitization, enhancing safety. Whether desensitization modulates drug allergic and anaphylactic responses facilitating tolerance is currently being investigated. This review provides insight into the current knowledge of drug allergy and anaphylaxis to cancer and chronic inflammatory diseases drugs, the mechanisms of drug desensitization and its applications to personalized medicine.

Tumor Response and Apoptosis of N1-S1 Rodent Hepatomas in Response to Intra-arterial and Intravenous Benzamide Riboside

International Nuclear Information System (INIS)

McLennan, Gordon; Bennett, Stacy L.; Ju, Shenghong; Babsky, Andriy; Bansal, Navin; Shorten, Michelle L.; Levitin, Seth; Bonnac, Laurent; Panciewicz, Krystoff W.; Jayaram, Hiramagular N.

2012-01-01

Purpose: Benzamide riboside (BR) induces tumor apoptosis in multiple cell lines and animals. This pilot study compares apoptosis and tumor response in rat hepatomas treated with hepatic arterial BR (IA) or intravenous (IV) BR. Methods: A total of 10 6 N1-S1 cells were placed in the left hepatic lobes of 15 Sprague-Dawley rats. After 2 weeks, BR (20 mg/kg) was infused IA (n = 5) or IV (n = 5). One animal in each group was excluded for technical factors, which prevented a full dose administration (1 IA and 1 IV). Five rats received saline (3 IA and 2 IV). Animals were killed after 3 weeks. Tumor volumes after IA and IV treatments were analyzed by Wilcoxon rank sum test. The percentage of tumor and normal liver apoptosis was counted by using 10 fields of TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-stained slides at 40× magnification. The percentage of apoptosis was compared between IV and IA administrations and with saline sham-treated rats by the Wilcoxon rank sum test. Results: Tumors were smaller after IA treatment, but this did not reach statistical significance (0.14 IA vs. 0.57 IV; P = 0.138). There was much variability in percentage of apoptosis and no significant difference between IA and IV BR (44.49 vs. 1.52%; P = 0.18); IA BR and saline (44.49 vs. 33.83%; P = 0.66); or IV BR and saline (1.52 vs. 193%; P = 0.18). Conclusions: Although differences in tumor volumes did not reach statistical significance, there was a trend toward smaller tumors after IA BR than IV BR in this small pilot study. Comparisons of these treatment methods will require a larger sample size and repeat experimentation.

[Oral rush desensitization for cow milk allergy: Clinical and immunological follow-up].

Science.gov (United States)

González Jiménez, D; Larrea Tamayo, E; Díaz Martin, J J; Molinos Norniella, C; Pérez Solis, D; Menéndez Arias, C; Jiménez Treviño, S; Bousoño García, C

2013-12-01

The aim of this study was to evaluate the safety and efficacy of oral rush desensitization in children with cow milk allergy. Prospective study. We included IgE-mediated cow milk allergy children over 3 years in 3 Spanish hospitals. Increasing doses of cow milk for 5 days from 1 cc of 1% to 200 cc of pure milk were administered. Clinical follow-up was conducted and we compared specific IgE levels at onset, 6, 12 and 24 months after desensitization. We included 18 children (13 males) between 3 and 14 years (mean 5.96). A total of 271 doses were administered; there were 55 adverse reactions (84% mild). At the end of the protocol, 100% showed some degree of tolerance (39% total). Full tolerance was achieved in 72% of patients after two years. Two children failed to achieve tolerance. There was a significant decrease in the levels of specific IgE to cow milk and alpha-lactalbumin at 24 months, and to casein at 6, 12 and 24 months, compared to baseline. Oral rush desensitization is a safe and effective therapeutic option for patients with persistent cow milk allergy to medium term. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Effectiveness of cognitive behavioral therapy integrated with systematic desensitization, cognitive behavioral therapy combined with eye movement desensitization and reprocessing therapy, and cognitive behavioral therapy combined with virtual reality exposure therapy methods in the treatment of flight anxiety: a randomized trial.

Science.gov (United States)

Triscari, Maria Teresa; Faraci, Palmira; Catalisano, Dario; D'Angelo, Valerio; Urso, Viviana

2015-01-01

The purpose of the research was to compare the effectiveness of the following treatment methods for fear of flying: cognitive behavioral therapy (CBT) integrated with systematic desensitization, CBT combined with eye movement desensitization and reprocessing therapy, and CBT combined with virtual reality exposure therapy. Overall, our findings have proven the efficacy of all interventions in reducing fear of flying in a pre- to post-treatment comparison. All groups showed a decrease in flight anxiety, suggesting the efficiency of all three treatments in reducing self-report measures of fear of flying. In particular, our results indicated significant improvements for the treated patients using all the treatment programs, as shown not only by test scores but also by participation in the post-treatment flight. Nevertheless, outcome measures maintained a significant effect at a 1-year follow-up. In conclusion, combining CBT with both the application of eye movement desensitization and reprocessing treatment and the virtual stimuli used to expose patients with aerophobia seemed as efficient as traditional cognitive behavioral treatments integrated with systematic desensitization.

Effect of an experimental desensitizing agent on reduction of bleaching-induced tooth sensitivity: A triple-blind randomized clinical trial.

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Parreiras, Sibelli Olivieri; Szesz, Anna Luiza; Coppla, Fabiana Madalozzo; Martini, Eveline Claudia; Farago, Paulo Vitor; Loguercio, Alessandro D; Reis, Alessandra

2018-04-01

In this randomized study, split-mouth, triple-blind clinical trial, the authors evaluated the efficacy of a desensitizing gel that contained 5% potassium nitrate and 5% glutaraldehyde applied before in-office bleaching with 35% hydrogen peroxide (HP). Treatment with the desensitizing or placebo control gels was randomly assigned to one-half of the maxillary teeth of 42 patients in a split-mouth design. The desensitizing gels were applied and maintained in contact with the tooth enamel for 10 minutes, followed by 2 HP bleaching sessions separated by 1 week. The primary outcome variable was pain intensity assessed with a numeric rating scale and a visual analog scale. Color was evaluated by means of a digital spectrophotometer and a value-oriented shade guide. The difference in risk of developing tooth sensitivity between the desensitizing gel group (31.7%, 95% confidence interval [CI], 19.6 to 46.9) and the control group (70.7%; 95% CI, 55.5 to 82.3%) was statistically significant (P whitening reduced the risk and severity of dental sensitivity, without altering the effectiveness of whitening. A single application of desensitizing gel that contained 5% potassium nitrate and 5% glutaraldehyde can reduce tooth sensitivity after dental bleaching systems. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of oral desensitization in children with cow's milk allergy according to their serum specific IgE level.

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García-Ara, Carmen; Pedrosa, María; Belver, María Teresa; Martín-Muñoz, María Flor; Quirce, Santiago; Boyano-Martínez, Teresa

2013-04-01

Oral desensitization in children allergic to cow's milk proteins is not risk free. The analysis of factors that may influence the outcome is of utmost importance. To analyze the efficacy and safety of the oral desensitization according to specific IgE (sIgE) level and adverse events during the maintenance phase. Thirty-six patients allergic to cow's milk (mean age, 7 years) were included in an oral desensitization protocol. Patients were grouped according to sIgE levels (ImmunoCAP) into groups 1 (sIgE 17-50 kU/L). Nineteen children were included as a control group. Serum sIgE levels to cow's milk and its proteins were determined at inclusion and 6 and 12 months after finishing the desensitization protocol. Thirty-three of 36 patients were successfully desensitized (200 mL): 100% of group 1 and 88% of groups 2 and 3. Desensitization was achieved in a median of 3 months (range, 1-12 months); 90% of the patients in group 1, 50% of the patients in group 2, and 30% of the patients in group 3 achieved tolerance in less than 3 months (P = .04). In the control group only 1 child tolerated milk in oral food challenge after 1 year. During the induction phase, there were 53 adverse events in 27 patients (75%). Patients of groups 2 and 3 had more severe adverse events compared with group 1. During the maintenance phase, 20 of 33 patients (60%) had an adverse event. Oral desensitization is efficacious. Tolerance is achieved earlier when sIgE is lower. Severe adverse events are frequent, especially in patients with higher sIgE levels. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Angiotensin II (AngII) induces the expression of suppressor of cytokine signaling (SOCS)-3 in rat hypothalamus - a mechanism for desensitization of AngII signaling.

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Torsoni, Márcio A; Carvalheira, José B; Calegari, Vivian C; Bezerra, Rosangela M N; Saad, Mário J A; Gontijo, José A; Velloso, Lício A

2004-04-01

Angiotensin II exerts a potent dypsogenic stimulus on the hypothalamus, which contributes to its centrally mediated participation in the control of water balance and blood pressure. Repetitive intracerebroventricular (i.c.v.) injections of angiotensin II lead to a loss of effect characterized as physiological desensitization to the peptide's action. In the present study, we demonstrate that angiotensin II induces the expression of suppressor of cytokine signaling (SOCS)-3 via angiotensin receptor 1 (AT1) and JAK-2, mostly located at the median preoptic lateral and anterodorsal preoptic nuclei. SOCS-3 produces an inhibitory effect upon the signal transduction pathways of several cytokines and hormones that employ members of the JAK/STAT families as intermediaries. The partial inhibition of SOCS-3 translation by antisense oligonucleotide was sufficient to significantly reduce the refractoriness of repetitive i.c.v. angiotensin II injections, as evaluated by water ingestion. Thus, by acting through AT1 on the hypothalamus, angiotensin II induces the expression of SOCS-3 which, in turn, blocks further activation of the pathway and consequently leads to desensitization to angiotensin II stimuli concerning its dypsogenic effect.

Emotionally Numb: Desensitization to Community Violence Exposure among Urban Youth

Science.gov (United States)

Kennedy, Traci M.; Ceballo, Rosario

2016-01-01

Community violence exposure (CVE) is associated with numerous psychosocial outcomes among youth. Although linear, cumulative effects models have typically been used to describe these relations, emerging evidence suggests the presence of curvilinear associations that may represent a pattern of emotional desensitization among youth exposed to…

Renal transplantation across the donor-specific antibody barrier: Graft outcome and cancer risk after desensitization therapy.

Science.gov (United States)

Yang, Ching-Yao; Lee, Chih-Yuan; Yeh, Chi-Chuan; Tsai, Meng-Kun

2016-06-01

Desensitization regimens including use of intravenous immune globulin and rituximab have been reported to overcome renal transplant hyperacute rejection. A retrospective case-control study was performed to assess the results and complications of renal transplantation with desensitization therapy for donor-specific antibody (DSA) in a transplant center in Asia, where donor exchange was usually not allowed. Between January 2007 and December 2013, 22 patients with DSA received live-donor renal transplantation after desensitization (DSA group). During the same period, the DSA group was compared to the NSA group (152 renal transplants) who had no specific antibody to the donors (66 from deceased donors and 86 from living relatives). Rejection, renal function, graft and patient survival rates, infection, and cancer incidence were reviewed and analyzed from medical records. The DSA group (46.8%) had significantly higher acute rejection rates than the NSA group (13.7%) at the 1-year follow-up. The estimated renal function, 5-year graft, and patient survival rates were comparable between the groups. The DSA group (19.6%) had significantly higher 5-year de novo cancer incidence than the NSA group (8.5%; p = 0.028); three patients of the DSA group developed urothelial carcinoma 17.0 ± 3.0 months after transplantation. By using stepwise Cox regression analysis, desensitization therapy was identified as the sole independent risk factor for post-transplant urothelial carcinoma. When compared to renal transplantation without DSA, desensitization therapy for DSA resulted in equivalent renal transplant outcome but potentially increased risk of urothelial carcinoma after transplantation. Copyright © 2015. Published by Elsevier B.V.

Impact of Gluma Desensitizer on the tensile strength of zirconia crowns bonded to dentin: an in vitro study.

Science.gov (United States)

Stawarczyk, Bogna; Hartmann, Leonie; Hartmann, Rahel; Roos, Malgorzata; Ender, Andreas; Ozcan, Mutlu; Sailer, Irena; Hämmerle, Christoph H F

2012-02-01

This study tested the impact of Gluma Desensitizer on the tensile strength of zirconia crowns bonded to dentin. Human teeth were prepared and randomly divided into six groups (N = 144, n = 24 per group). For each tooth, a zirconia crown was manufactured. The zirconia crowns were cemented with: (1) Panavia21 (PAN), (2) Panavia21 combined with Gluma Desensitizer (PAN-G), (3) RelyX Unicem (RXU), (4) RelyX Unicem combined with Gluma Desensitizer (RXU-G), (5) G-Cem (GCM) and (6) G-Cem combined with Gluma Desensitizer (GCM-G). The initial tensile strength was measured in half (n = 12) of each group and the other half (n = 12) subjected to a chewing machine (1.2 Mio, 49 N, 5°C/50°C). The cemented crowns were pulled in a Universal Testing Machine (1 mm/min, Zwick Z010) until failure occurred and tensile strength was calculated. Data were analyzed with one-way and two-way ANOVA followed by a post hoc Scheffé test, t test and Kaplan-Meier analysis with a Breslow-Gehan analysis test (α = 0.05). After the chewing simulation, the self-adhesive resin cements combined with Gluma Desensitizer showed significantly higher tensile strength (RXU-G, 12.8 ± 4.3 MPa; GCM-G, 13.4 ± 6.2 MPa) than PAN (7.3 ± 1.7 MPa) and PAN-G (0.9 ± 0.6). Within the groups, PAN, PAN-G and RXU resulted in significantly lower values when compared to the initial tensile strength; the values of all other test groups were stable. In this study, self-adhesive resin cements combined with Gluma Desensitizer reached better long-term stability compared to PAN and PAN-G after chewing simulation.

GEP100/Arf6 is required for epidermal growth factor-induced ERK/Rac1 signaling and cell migration in human hepatoma HepG2 cells.

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ZhenZhen Hu

Full Text Available BACKGROUND: Epidermal growth factor (EGF signaling is implicated in the invasion and metastasis of hepatoma cells. However, the signaling pathways for EGF-induced motility of hepatoma cells remain undefined. METHODOLOGY/PRINCIPAL FINDINGS: We found that EGF dose-dependently stimulated the migration of human hepatoma cells HepG2, with the maximal effect at 10 ng/mL. Additionally, EGF increased Arf6 activity, and ectopic expression of Arf6 T27N, a dominant negative Arf6 mutant, largely abolish EGF-induced cell migration. Blocking GEP100 with GEP100 siRNA or GEP100-△PH, a pleckstrin homology (PH domain deletion mutant of GEP100, blocked EGF-induced Arf6 activity and cell migration. EGF also increased ERK and Rac1 activity. Ectopic expression GEP100 siRNA, GEP100-△PH, or Arf6-T27N suppressed EGF-induced ERK and Rac1 activity. Furthermore, blocking ERK signaling with its inhibitor U0126 remarkably inhibited both EGF-induced Rac1 activation as well as cell migration, and ectopic expression of inactive mutant form of Rac1 (Rac1-T17N also largely abolished EGF-induced cell migration. CONCLUSIONS/SIGNIFICANCE: Taken together, this study highlights the function of the PH domain of GEP100 and its regulated Arf6/ERK/Rac1 signaling cascade in EGF-induced hepatoma cell migration. These findings could provide a rationale for designing new therapy based on inhibition of hepatoma metastasis.

Clinical approach on challenge and desensitization procedures with aspirin in patients with ischemic heart disease and nonsteroidal anti-inflammatory drug hypersensitivity.

Science.gov (United States)

Cortellini, G; Romano, A; Santucci, A; Barbaud, A; Bavbek, S; Bignardi, D; Blanca, M; Bonadonna, P; Costantino, M T; Laguna, J J; Lombardo, C; Losappio, L M; Makowska, J; Nakonechna, A; Quercia, O; Pastorello, E A; Patella, V; Terreehorst, I; Testi, S; Cernadas, J R; Dionicio Elera, J; Lippolis, D; Voltolini, S; Grosseto, D

2017-03-01

Hypersensitivity to acetylsalicylic acid (ASA) constitutes a serious problem for subjects with coronary artery disease. In such subjects, physicians have to choose the more appropriate procedure between challenge and desensitization. As the literature on this issue is sparse, this study aimed to establish in these subjects clinical criteria for eligibility for an ASA challenge and/or desensitization. Collection and analysis of data on ASA challenges and desensitizations from 10 allergy centers, as well as consensus among the related physicians and an expert panel. Altogether, 310 subjects were assessed; 217 had histories of urticaria/angioedema, 50 of anaphylaxis, 26 of nonimmediate cutaneous eruptions, and 17 of bronchospasm related to ASA/nonsteroidal anti-inflammatory drugs (NSAID) intake. Specifically, 119 subjects had index reactions to ASA doses lower than 300 mg. Of the 310 subjects, 138 had an acute coronary syndrome (ACS), 101 of whom underwent desensitizations, whereas 172 suffered from a chronic ischemic heart disease (CIHD), 126 of whom underwent challenges. Overall, 163 subjects underwent challenges and 147 subjects underwent desensitizations; 86 of the latter had index reactions to ASA doses of 300 mg or less. Ten subjects reacted to challenges, seven at doses up to 500 mg, three at a cumulative dose of 110 mg. The desensitization failure rate was 1.4%. In patients with stable CIHD and histories of nonsevere hypersensitivity reactions to ASA/NSAIDs, an ASA challenge is advisable. Patients with an ACS and histories of hypersensitivity reactions to ASA, especially following doses lower than 100 mg, should directly undergo desensitization. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice.

Science.gov (United States)

Gainetdinov, R R; Bohn, L M; Walker, J K; Laporte, S A; Macrae, A D; Caron, M G; Lefkowitz, R J; Premont, R T

1999-12-01

G protein-coupled receptor kinase 5 (GRK5) is a member of a family of enzymes that phosphorylate activated G protein-coupled receptors (GPCR). To address the physiological importance of GRK5-mediated regulation of GPCRs, mice bearing targeted deletion of the GRK5 gene (GRK5-KO) were generated. GRK5-KO mice exhibited mild spontaneous hypothermia as well as pronounced behavioral supersensitivity upon challenge with the nonselective muscarinic agonist oxotremorine. Classical cholinergic responses such as hypothermia, hypoactivity, tremor, and salivation were enhanced in GRK5-KO animals. The antinociceptive effect of oxotremorine was also potentiated and prolonged. Muscarinic receptors in brains from GRK5-KO mice resisted oxotremorine-induced desensitization, as assessed by oxotremorine-stimulated [5S]GTPgammaS binding. These data demonstrate that elimination of GRK5 results in cholinergic supersensitivity and impaired muscarinic receptor desensitization and suggest that a deficit of GPCR desensitization may be an underlying cause of behavioral supersensitivity.

Perbedaan Penggunaan Bahan Desensitizing dan Tanpa Desensitizing Pasca Bleaching Ekstra-Koronal terhadap Kekerasan Email

Directory of Open Access Journals (Sweden)

Wignyo Hadriyanto

2012-12-01

Full Text Available Latar Belakang. Pada bleaching ekstrakoronal diketahui terjadi proses demineralisasi sehingga terjadi hiersensitivitas dentin. UltraEZ salah satu bahan desensitizing yang dapat mengurangi hipersensitivitas akibat demineralisasi email pasca bleaching ekstrakoronal terkini. Tujuan penelitian ini bertujuan untuk mengetahui perbedaan kekerasan email pasca pemutihan gigi ekstra-koronal dengan aplikasi bahan desensitizing dan tanpa aplikasi bahan desensitizing. Metode penelitian ini menggunakan 20 gigi premolar permanen pasca pencabutanyang masih utuh dan direndam dalam saliva buatan, kemudian dilakukan pemolesan pada bagian bukal dengan menggunakan pasta profilaksis kemudian gigi dicuci dan dikeringkan. Bahan pemutih Opalescence Xtra Boost diaplikasikan pada semua permukaan bukal gigi premolar kemudian dibagi menjadi 2 kelompok yaitu kelompok I, II, masing-masing kelompok sebanyak 10 gigi. Kelompok I sebagai kelompok control setelah dilakukan pemutihan, tidak dilakukan aplikasi Ultra-EZ, dimasukkan dalam wadah botol dan direndam dalam saliva buatan kemudian disimpan dalam incubator. Mahkota dan akar gigi,kemudian ditanam dalam resin akrilik sesuai kelompok sebelumnya dengan permukaan bukal menghadap ke atas. Semua sampel diuji kekerasannya dengan uji kekerasan Vickers menggunakan beban 100 g selama 15 detik. Permukaan bukal menghadap ke atas, kemudian dijepit dengan alat penjepit pada meja alat Micro Vickers Hardness Tester. Sampel diatur sedemikian rupa sehingga akan terlihat gambar yang dapat diukur panjang diagonalnya langsung dengan micrometer yang ada pada lensa okuler. Nilai kekerasan email dalam Vickers hardness number (VHN juga dapat diperoleh dari table setelah mengetahui rata-rata panjang diagonal, berat badan yang digunakan dan waktu yang digunakan untuk uji kekerasan. Pengujian ini dilakukan pada setiap kelompok. Selanjutnya diuji dengan uji-t. hasil penelitian menunjukkan ada perbedaan yang bermakna antara aplikasi ultraEZ lima menit

Comparing the Effectiveness of Systematic Desensitization and Distraction on Pain and Fear in Children with Dental Problems

Directory of Open Access Journals (Sweden)

Maryam Fallah

2016-04-01

Full Text Available Background & objectives: One of the difficulties of community of dentists, especially dentists dealing with children, is the pain and fear of dental treatment. The purpose of this study was to investigate the effectiveness of systematic desensitization and distraction on reducing fear and pain in children with dental problems. Methods: This is a quasi-experimental study designed with pretest-posttest multi groups according to control group. For this purpose, 45 children with dental problems referred to the dental clinic of Ardabil was selected and divided into three groups of 15 people: systematic desensitization (n=15, distraction (n=15 and control group (n=15. All of three groups answered to dental fears survey and numeric scale of pain as pre-test. Then, the therapeutic method of systematic desensitization and distraction was performed on two experimental groups. After completion of the treatments, three groups answered to dental fear survey and numeric scale of pain. Multivariate analysis of covariance was used for the analysis of the data. Results: The results showed a significant difference in the score of post-test between three groups in pain (F=197.27; p<0.001 anddental fear (F=178.36; p<0.001. LSD post hoc test results showed that systematic desensitization method was more effective in reduction of pain and the distraction method was more affective in reduction of dental fear. Conclusion: The results of this study indicate that psychological interventions of distracting and systematic desensitization can be used to reduce fear and pain at pediatric clinics.

Effects of a traditional chinese medicine based desensitizing gel on ...

African Journals Online (AJOL)

Background and Objective: Bamboo salt, Calcined oyster, Drynaria fortunei, Indigo naturalis and Rehmannia glutinosa have been the main ingredients of many formulations in Chinese medicine for the treatment of toothache. This study evaluated the effect of a new desensitizing gel on dentin hypersensitivity (DH). Materials ...

Origin, development, and evolution of eye movement desensitization and reprocessing

Directory of Open Access Journals (Sweden)

Carolina Marín

2016-12-01

Full Text Available Eye movement desensitization and reprocessing (EMDR has led to a great number of studies since its appearance in 1989. The aim of this article is to describe EMDR development and evolution to the present day. With this purpose a search was carried out on MEDLINE and PsycINFO with the entry "eye movement desensitization". After revising the resulting 797 articles, those that because of their relevance explained best the development and evolution of the technique were chosen and shaped into a lifeline graphically representing the history of EMDR. Despite the fact that during the first years the focus of research was on the validation of the technique for post-traumatic disorder (PTSD, it was soon applied to other areas. Only 14% of the articles found account for controlled studies. Up to date, in spite of the effectiveness of EMDR for the treatment of PTSD that has been proven, many different explanatory hypotheses are still up for discussion.

Hydrodynamic properties of the gonadotropin receptor from a murine Leydig tumor cell line are altered by desensitization

International Nuclear Information System (INIS)

Rebois, R.V.; Bradley, R.M.; Titlow, C.C.

1987-01-01

The murine Leydig tumor cell line 1 (MLTC-1) contains gonadotropin receptors (GR) that are coupled to adenylate cyclase through the stimulatory guanine nucleotide binding protein (G/sub s/). The binding of human choriogonadotropin (hGC) causes MLTC-1 cells to accumulate cAMP. With time, the ability of MLTC-1 cells to respond to hCG is attenuated by a process called desensitization. The hydrodynamic properties of GR from control and desensitized MLTC-1 cells were studied. Sucrose density gradient sedimentation in H 2 O and D 2 O and gel filtration chromatography were used to estimate the Stokes radius (a), partial specific volume (v/sub c/), sedimentation coefficient (s/sub 20,w/), and molecular weight (M/sub r/) of the detergent-solubilized hormone-receptor complex (hCG-GR). [ 125 I]hCG was bound to MLTC-1 cells under conditions that allow (37 0 C) or prevent (0 0 C) desensitization, and hCG-GR was solubilized in Triton X-100. In the absence of desensitization, control hCG-GR had a M/sub r/ of 213,000, whereas desensitized hCG-GR had a M/sub r/ of 158,000. Deglycosylated hCG (DG-HCG) is an antagonist that binds to GR with high affinity but fails to stimulate adenylate cyclase or cause desensitization. [ 125 I]DG-hCG was bound to MLTC-1 cells and DG-hCG-GR solubilized in Triton X-100. The hydrodynamic properties of DG-hCG-GR were the same as that for control hCG-GR. There was no evidence for the association of adenylate cyclase or G/sub s/ with GR in Triton X-100 solubilized preparations. When hCG was cross-linked to GR and solubilized with sodium dodecyl sulfate (SDS), the M/sub r/ was found to be 116,000, which was similar to that determined by SDS-polyacrylamide gel electrophoresis and less than that of the Triton X-100 solubilized control hCG-GR

Eye Movement Desensitization and Reprocessing for Adolescent Depression

OpenAIRE

Bae, Hwallip; Kim, Daeho; Park, Yong Chon

2008-01-01

While cognitive behavior therapy is considered to be the first-line therapy for adolescent depression, there are limited data on whether other psychotherapeutic techniques are also effective in treating adolescents with depression. This report suggests the potential application of eye movement desensitization and reprocessing (EMDR) for treatment of depressive disorder related, not to trauma, but to stressful life events. At present, EMDR has only been empirically validated for only trauma-re...

Enzyme-potentiated desensitization in otolaryngic allergy.

Science.gov (United States)

Pulec, Jack L

2002-03-01

This is a preliminary report of a new method of treating otolaryngic allergy with enzyme-potentiated desensitization (EPD). The nature of EPD and its use in otolaryngology are described. Thirty-six patients have been treated and followed in a private medical practice since February 1997. This article reviews the clinical features of EPD and provides six cases as examples; the clinical features described include allergic rhinitis, serous otitis media, asthma, dermatitis, fixed food allergy, and Ménière's disease. EPD is an effective technique for the treatment of otolaryngic allergy and offers advantages over conventional techniques.

Emotional and Physiological Desensitization to Real-Life and Movie Violence

Science.gov (United States)

Mrug, Sylvie; Madan, Anjana; Cook, Edwin W.; Wright, Rex A.

2014-01-01

Youth are exposed to large amounts of violence in real life and media, which may lead to desensitization. Given evidence of curvilinear associations between exposure to violence and emotional distress, we examined linear and curvilinear associations of exposure to real-life and movie violence with PTSD symptoms, empathy, and physiological arousal, as well emotional and physiological reactivity to movie violence. College students (N=209; mean age=18.74) reported on their exposure to real-life and televised violence, PTSD symptoms, and empathy. Then, students were randomly assigned to view a series of violent or nonviolent high-action movie scenes, providing ratings of emotional distress after each clip. Blood pressure was measured at rest and during video viewing. Results showed that with increasing exposure to real-life violence, youth reported more PTSD symptoms and greater identification with fictional characters. Cognitive and emotional empathy increased from low to medium levels of exposure to violence, but declined at higher levels. For males, exposure to higher levels of real-life violence was associated with diminishing (vs. increasing) emotional distress when viewing violent videos. Exposure to televised violence was generally unrelated to emotional functioning. However, those with medium levels of exposure to TV/movie violence experienced lower elevations of blood pressure when viewing violent videos compared to those with low exposure, and those with higher levels of exposure evidenced rapid increase in blood pressure that quickly declined over time. The results point to diminished empathy and reduced emotional reactivity to violence as key aspects of desensitization to real-life violence, and more limited evidence of physiological desensitization to movie violence among those exposed to high levels of televised violence. PMID:25326900

Diagnostic application of Ga-67 scintigraphy in primary lung cancer, hepatoma and abdominal abscess. On surgical operation

Energy Technology Data Exchange (ETDEWEB)

Oshiumi, Yoshihiko (National Central Hospital of Fukuoka (Japan))

1983-05-01

It is difficult to detect tumor lesions by /sup 67/Ga-scintigraphy, though it is named as a tumor scintigraphy. Recently, /sup 67/Ga-scintigraphy is well used in the detection of inflammatic lesions. This paper is to discuss the detectability of lesions and diagnostic limitation on operability by /sup 67/Ga-scintigraphy to primary lung cancer, minute hepatoma and abdominal abscess. Primary lung cancer: In detecting metastatic hilar lymph nodes, the sensitivity is 54%, and the specificity is 78%. In detecting metastatic mediastinal lymph nodes, the sensitivity is 32% and the specificity is 89%. Minute hepatoma : The detectability depended on the size of the lesion. It is hard to detect lesions with under 2 cm by /sup 67/Ga-scintigraphy. Abdominal abscess : The sensitivity is 88%, and the specificity is 92%.

Role of desensitization and subunit expression for kainate receptor-mediated neurotoxicity in murine neocortical cultures

DEFF Research Database (Denmark)

Jensen, J B; Schousboe, A; Pickering, D S

1999-01-01

) toxicity mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors, and (3) toxicity that can be mediated by kainate receptors when desensitization of the receptors is blocked. The indirect action at NMDA receptors was discovered because (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H...... nedioxy-5H-2,3-benzodiazepine (GYKI 53655), a selective AMPA receptor antagonist, abolished the remaining toxicity. These results indicated that kainate- and domoate-mediated toxicity involves both the NMDA and the AMPA receptors. Pretreatment of the cultures with concanavalin A to prevent desensitization...

Synergistic effect of intervention of glypican-3 gene transcription combined with antitumor drugs in inhibiting hepatoma cell proliferation

Directory of Open Access Journals (Sweden)

YANG Jie

2016-12-01

Full Text Available ObjectiveTo investigate the inhibitory effect of intervention of glypican-3 (GPC3 gene transcription combined with antitumor drugs on hepatoma cell proliferation. MethodsFour types of GPC3-shRNA plasmids were established and transfected into HepG2 hepatoma cells. Quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression of GPC3 to analyze its association with hepatoma cell proliferation and apoptosis. The independent samples t-test was used for comparison of continuous data between any two groups, and a one-way analysis of variance was used for comparison between multiple groups. ResultsAmong these four plasmids, shRNA1 had a transfection efficiency of ＞85% in the transfection of HepG2 cells and a silence efficiency of 89.3% at the mRNA level, and the protein expression of GPC3 was significantly inhibited(P＜0.01）. At 72 hours, the GPC3-shRNA1 co-intervention group had an HepG2 cell inhibition rate of 71.1%, significantly different from that in the negative group (t=18.092, P＜0.001, an inhibition rate of migration of 89.1%, significantly lower than that in the negative group (t=8.326, P＜0.001, and inhibition rates of HepG2 cell movement and invasion of 53.6% and 60.1%, which were significantly different from those in the negative group (t=52.400 and 48.245, both P＜0.001. The GPC3-shRNA1 co-intervention group had a β-catenin mRNA inhibition rate of 46.9% and a Gli1 mRNA upregulation rate of 7.4%, significantly different from those in the negative group (t=30.108 and -3.551, P＜0.001 and P=0.009. At 24 hours, 10 μmol/L sorafenib combined with shRNA1 had an inhibition rate of tumor cells of 52.6% and 100 μmol/L sorafenib combined with shRNA1 had an inhibition rate of tumor cells of 79.5%, which were significantly different from that in the control group (t=23.314 and 50.352, both P＜0.001. The half-maximal inhibitory concentrations of sorafenib, rapamycin, and erlotinib for HepG2 were 4.67±1

Desensitization in delayed drug hypersensitivity reactions -- an EAACI position paper of the Drug Allergy Interest Group.

Science.gov (United States)

Scherer, K; Brockow, K; Aberer, W; Gooi, J H C; Demoly, P; Romano, A; Schnyder, B; Whitaker, P; Cernadas, J S R; Bircher, A J

2013-07-01

Drug hypersensitivity may deprive patients of drug therapy, and occasionally no effective alternative treatment is available. Successful desensitization has been well documented in delayed drug hypersensitivity reactions. In certain situations, such as sulfonamide hypersensitivity in HIV-positive patients or hypersensitivity to antibiotics in patients with cystic fibrosis, published success rates reach 80%, and this procedure appears helpful for the patient management. A state of clinical tolerance may be achieved by the administration of increasing doses of the previously offending drug. However, in most cases, a pre-existent sensitization has not been proven by positive skin tests. Successful re-administration may have occurred in nonsensitized patients. A better understanding of the underlying mechanisms of desensitization is needed. Currently, desensitization in delayed hypersensitivity reactions is restricted to mild, uncomplicated exanthems and fixed drug eruptions. The published success rates vary depending on clinical manifestations, drugs, and applied protocols. Slower protocols tend to be more effective than rush protocols; however, underreporting of unsuccessful procedures is very probable. The decision to desensitize a patient must always be made on an individual basis, balancing risks and benefits. This paper reviews the literature and presents the expert experience of the Drug Hypersensitivity Interest Group of the European Academy of Allergy and Clinical Immunology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Radiation induced bystander effect on hepatoma HepG2 cells under hypoxia condition

International Nuclear Information System (INIS)

Zhang Jianghong; Jin Yizun; Shao Chunlin; Prise KM

2009-01-01

Objective: To investigate radiation induced bystander effect and its mechanism on hepatoma HepG2 cells under hypoxia condition. Methods: Non-irradiated bystander hepatoma cells were co-cultured with irradiated cells or treated with the conditioned medium (CM) from irradiated cells, then micronuclei (MN) were measured for both irradiated cells and bystander cells. Results: The MN yield of irradiated HepG2 cells under hypoxic condition was significantly lower than that under normoxia, the oxygen enhancement ratio of HepG2 cells of MN was 1.6. For both hypoxic and normoxic condition, the MN yield of bystander cells were obviously enhanced to a similar high level after co-culturing with irradiated cells or with CM treatment, and it also correlated with the irradiation dose. When the hypoxic HepG2 cells were treated with either DMSO, a scavenger of reactive oxygen species (ROS), or aminoguanidine, an iNOS inhibitor, the yield of bystander MN was partly diminished, and the reducing rate of DMSO was 42.2%-46.7%, the reducing rate of aminoguanidine was 42% . Conclusion: ROS, NO and their downstream signal factors are involved in the radiation induced bystander effect of hypoxic HepG2 cells. (authors)

Apoptosis and changes in glucose transport early after treatment of Morris hepatoma with gemcitabine

International Nuclear Information System (INIS)

Haberkorn, U.; Bellemann, M.E.; Brix, G.; Kamencic, H.; Traut, U.; Kinscherf, R.; Doll, J.; Blatter, J.

2001-01-01

Apoptosis has been described as an energy-consuming process. This combined in vivo/in vitro study investigated the effects of the antineoplastic agent gemcitabine on tumour metabolism and on the induction of apoptosis. Dynamic positron emission tomography (PET) measurements of fluorine-18 fluorodeoxyglucose (FDG) uptake were done in rats bearing Morris hepatoma prior to and after therapy with 90 mg gemcitabine/kg b.w. Furthermore, thymidine (TdR) incorporation into the DNA of these tumours was determined. In vitro measurements of FDG and TdR uptake were performed immediately and 24 h after the end of gemcitabine treatment, and the amount of apoptotic cells was determined using the TUNEL reaction. In vivo an increase in FDG transport and phosphorylation occurred early after gemcitabine treatment, although TdR incorporation into the DNA of the tumours declined. In vitro, an enhanced glucose transport, an increase in TdR uptake in the cytoplasm and a decrease in TdR incorporation in the nucleic acid fraction early after treatment occurred. Inhibition of glucose transport caused an increase in the amount of apoptotic cells. The increase in glucose uptake and TdR metabolism early after therapy is interpreted as a stress reaction of the tumour cells, protecting the cells from apoptosis during this early period after exposure to cytotoxic drugs like gemcitabine. (orig.)

Apoptosis and changes in glucose transport early after treatment of Morris hepatoma with gemcitabine

Energy Technology Data Exchange (ETDEWEB)

Haberkorn, U. [Heidelberg Univ. (Germany). Abt. fuer Klinische Nuklearmedizin; Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); Bellemann, M.E. [Department of Biomedical Engineering, University of Applied Sciences, Jena (Germany); Brix, G. [Department of Medical Radiation Hygiene, Federal Office for Radiation Protection, Neuherberg (Germany); Kamencic, H.; Traut, U.; Kinscherf, R. [Heidelberg Univ. (Germany). Inst. fuer Anatomie und Zellbiologie; Morr, I.; Altmann, A. [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); Doll, J. [Dept. of Medical Physics, German Cancer Research Center, Heidelberg (Germany); Blatter, J. [Lilly GmbH Germany, Bad Homburg (Germany)

2001-04-01

Apoptosis has been described as an energy-consuming process. This combined in vivo/in vitro study investigated the effects of the antineoplastic agent gemcitabine on tumour metabolism and on the induction of apoptosis. Dynamic positron emission tomography (PET) measurements of fluorine-18 fluorodeoxyglucose (FDG) uptake were done in rats bearing Morris hepatoma prior to and after therapy with 90 mg gemcitabine/kg b.w. Furthermore, thymidine (TdR) incorporation into the DNA of these tumours was determined. In vitro measurements of FDG and TdR uptake were performed immediately and 24 h after the end of gemcitabine treatment, and the amount of apoptotic cells was determined using the TUNEL reaction. In vivo an increase in FDG transport and phosphorylation occurred early after gemcitabine treatment, although TdR incorporation into the DNA of the tumours declined. In vitro, an enhanced glucose transport, an increase in TdR uptake in the cytoplasm and a decrease in TdR incorporation in the nucleic acid fraction early after treatment occurred. Inhibition of glucose transport caused an increase in the amount of apoptotic cells. The increase in glucose uptake and TdR metabolism early after therapy is interpreted as a stress reaction of the tumour cells, protecting the cells from apoptosis during this early period after exposure to cytotoxic drugs like gemcitabine. (orig.)

Slow desensitization of imatinib-induced nonimmediate reactions and dynamic changes of drug-specific CD4+CD25+CD134+ lymphocytes.

Science.gov (United States)

Klaewsongkram, Jettanong; Thantiworasit, Pattarawat; Sodsai, Pimpayao; Buranapraditkun, Supranee; Mongkolpathumrat, Pungjai

2016-11-01

Imatinib is a tyrosine kinase inhibitor indicated for the treatment of gastrointestinal stromal tumors (GISTs) and certain neoplastic diseases; however, nonimmediate adverse reactions are common. To describe the process of imatinib slow desensitization in patients who experienced nonimmediate reactions to imatinib and the dynamic change in drug-specific CD4 + CD25 + CD134 + T-lymphocyte percentages. Five patients diagnosed as having GISTs and with a recent history of imatinib-induced nonimmediate reactions (maculopapular exanthema with eosinophilia, exfoliative dermatitis, palmar-plantar erythrodysesthesia, and drug rash with eosinophilia and systemic symptoms) were desensitized using a slow desensitization protocol. The reintroduced imatinib dosage was stepped up every week starting from 10 mg/d and increasing to 25, 50, 75, 100, 150, 200, and 300 mg/d until the target dose of 400 mg/d was achieved. Prednisolone of up to 30 mg/d was allowed if allergic reactions recurred. The percentages of CD4 + CD25 + CD134 + T cells present after incubating peripheral blood mononuclear cells with imatinib, at baseline and after successful desensitization, were analyzed using flow cytometric analysis. By using a slow desensitization technique, all patients were able to receive 400 mg/d of imatinib, and prednisolone was gradually tapered off. The percentages of imatinib-induced CD4 + CD25 + CD134 + T cells decreased from a mean (SD) of 11.3% (6.5%) and 13.4% (7.3%) at baseline to 3.2% (0.7%) and 3.0% (1.1%) after successful desensitization, when stimulating peripheral blood mononuclear cells with 1 and 2 μM of imatinib, respectively. Slow desensitization is a helpful procedure in treating patients with imatinib-induced nonimmediate reactions other than simple maculopapular exanthema. The reduced percentages of imatinib-induced CD4 + CD25 + CD134 + T cells in these patients may be associated with immune tolerance. Copyright © 2016 American College of Allergy, Asthma & Immunology

Effects of currently used pesticides in the AhR-CALUX assay: comparison between the human TV101L and the rat H4IIE cell line

DEFF Research Database (Denmark)

Long, M.; Laier, Peter; Vinggaard, Anne

2003-01-01

TV101L hepatoma cell lines. In comparison the results indicated that the rat H4IIE cell line is more sensitive than the human TV101L for detection of TCDD inducing AhR-CALUX activity. The pesticides iprodione, chlorpyrifos and prochloraz showed dose-dependent AhR agonistic effects in both cell lines...

Channel opening of γ-aminobutyric acid receptor from rat brain: molecular mechanisms of the receptor responses

International Nuclear Information System (INIS)

Cash, D.J.; Subbarao, K.

1987-01-01

The function of γ-aminobutyric acid (GABA) receptors, which mediate transmembrane chloride flux, can be studied by use of 36 Cl - isotope tracer with membrane from mammalian brain by quench-flow technique, with reaction times that allow resolution of the receptor desensitization rates from the ion flux rates. The rates of chloride exchange into the vesicles in the absence and presence of GABA were characterized with membrane from rat cerebral cortex. Unspecific 36 Cl - influx was completed in three phases of ca. 3% (t/sub 1/2/ = 0.6 s), 56% (t/sub 1/2 = 82 s), and 41% (t/sub 1/2 = 23 min). GABA-mediated, specific chloride exchange occurred with 6.5% of the total vesicular internal volume. The GABA-dependent 36 Cl - influx proceeded in two phases, each progressively slowed by desensitization. The measurements supported the presence of two distinguishable active GABA receptors on the same membrane mediating chloride exchange into the vesicles. The half-response concentrations were similar for both receptors. The two receptors were present in the activity ratio of ca. 4/1, similar to the ratio of low affinity to high-affinity GABA sites found in ligand binding experiments. The desensitization rates have a different dependence on GABA concentration than the channel-opening equilibria. For both receptors, the measurements over a 2000-fold GABA concentration range required a minimal mechanism involving the occupation of both of the two GABA binding sites for significant channel opening; then the receptors were ca. 80% open. Similarly for both receptors, desensitization was mediated by a different pair of binding sites, although desensitization with only one ligand molecule bound could occur at a 20-fold slower rate

Violence exposure in real-life, video games, television, movies, and the internet: is there desensitization?

Science.gov (United States)

Funk, Jeanne B; Baldacci, Heidi Bechtoldt; Pasold, Tracie; Baumgardner, Jennifer

2004-02-01

It is believed that repeated exposure to real-life and to entertainment violence may alter cognitive, affective, and behavioral processes, possibly leading to desensitization. The goal of the present study was to determine if there are relationships between real-life and media violence exposure and desensitization as reflected in related characteristics. One hundred fifty fourth and fifth graders completed measures of real-life violence exposure, media violence exposure, empathy, and attitudes towards violence. Regression analyses indicated that only exposure to video game violence was associated with (lower) empathy. Both video game and movie violence exposure were associated with stronger proviolence attitudes. The active nature of playing video games, intense engagement, and the tendency to be translated into fantasy play may explain negative impact, though causality was not investigated in the present design. The samples' relatively low exposure to real-life violence may have limited the identification of relationships. Although difficult to quantify, desensitization to violence should be further studied using related characteristics as in the present study. Individual differences and causal relationships should also be examined.

Treatment of Nightmares via Relaxation and Desensitization: A Controlled Evaluation.

Science.gov (United States)

Miller, William R.; DiPilato, Marina

1983-01-01

Investigated the role of relaxation training as a component of desensitization to nightmares in adults (N=32). Results showed an 80 percent reduction in nightmares reported by 20 clients, of whom 12 reported total elimination of symptoms at 25-week follow-up, suggesting the effectiveness of a behavioral approach in treating nightmares. (LLL)

Desensitization for Drug Hypersensitivity to Chemotherapy and Monoclonal Antibodies.

Science.gov (United States)

Bonamichi-Santos, Rafael; Castells, Mariana

2016-01-01

Chemotherapies drugs and monoclonal antibodies are key components of the treatment of cancer patients and patients with chronic inflammatory conditions to provide increase in life expectancy and quality of life. Their increased use has lead to an increase in drugs hypersensitivity reactions (DHR) worldwide. DHR to those agents prevented their use and promoted the use of second line therapies to protect patients' hypersensitive reactions and anaphylaxis. Second line medications may not fully address the patients' medical condition and it is desirable to keep patients on first line therapy. Drug hypersensitivity symptoms can range from mild cutaneous reactions to life-threatening anaphylaxis. Rapid drug desensitization (RDD) is a novel approach to the management of drug hypersensitivity reactions which are IgE and non-IgE mediated. Through the diferent desensitization protocols patients can receive the full dose of the medications that they have presented a hypersensitive reaction and been protected against anaphylaxis. This review looks at the current literature on hypersensitivity reactions (HSR) to chemotherapy drugs and monoclonal antibodies and the potential use of RDD for their management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Immune Desensitization Allows Pediatric Blood Group Incompatible Kidney Transplantation.

Science.gov (United States)

Stojanovic, Jelena; Adamusiak, Anna; Kessaris, Nicos; Chandak, Pankaj; Ahmed, Zubir; Sebire, Neil J; Walsh, Grainne; Jones, Helen E; Marks, Stephen D; Mamode, Nizam

2017-06-01

Blood group incompatible transplantation (ABOi) in children is rare as pretransplant conditioning remains challenging and concerns persist about the potential increased risk of rejection. We describe the results of 11 ABOi pediatric renal transplant recipients in the 2 largest centers in the United Kingdom, sharing the same tailored desensitization protocol. Patients with pretransplant titers of 1 or more in 8 received rituximab 1 month before transplant; tacrolimus and mycophenolate mofetil were started 1 week before surgery. Antibody removal was performed to reduce titers to 1 or less in 8 on the day of the operation. No routine postoperative antibody removal was performed. Death-censored graft survival at last follow-up was 100% in the ABOi and 98% in 50 compatible pediatric transplants. One patient developed grade 2A rejection successfully treated with antithymocyte globulin. Another patient had a titer rise of 2 dilutions treated with 1 immunoadsorption session. There was no histological evidence of rejection in the other 9 patients. One patient developed cytomegalovirus and BK and 2 others EBV and BK viremia. Tailored desensitization in pediatric blood group incompatible kidney transplantation results in excellent outcomes with graft survival and rejection rates comparable with compatible transplants.

Catecholamine-induced desensitization of adenylate cyclase coupled β-adrenergic receptors in turkey erythrocytes: evidence for a two-step mechanism

International Nuclear Information System (INIS)

Stadel, J.M.; Rebar, R.; Crooke, S.T.

1987-01-01

Preincubation of turkey erythrocytes with isoproterenol is associated with (1) 50-60% attenuation of agonist-stimulated adenylate cyclase activity, (2) altered mobility of the β-adrenergic receptor on sodium dodecyl sulfate-polyacrylamide gels, and (3) increased phosphorylation of the β-adrenergic receptor. Using a low-cross-linked polyacrylamide gel, the β-adrenergic receptor protein from isoproterenol-desensitized cells, labeled with 32 P or with the photoaffinity label 125 I-(p-azidobenzyl)carazolol, can be resolved into a doublet (M/sub r/ similarly ordered 37,000 and M/sub r/ similarly ordered 41,000) as compared to a single M/sub r/ similarly ordered 37,000 β-adrenergic receptor protein from control erythrocytes. The appearance of the doublet was dependent on the concentration of agonist used to desensitize the cells. Incubation of erythrocytes with dibutyryl-cAMP did not promote formation of the doublet but decreased agonist-stimulated adenylate cyclase activity 40-50%. Limited-digestion peptide maps of 32 P-labeled β-adrenergic receptors using papain revealed a unique phosphopeptide in the larger molecular weight band (M/sub r/ similarly ordered 41,000) of the doublet from the agonist-desensitized preparation that was absent in the peptide maps of the smaller band (M/sub r/ similarly ordered 37,000), as well as control or dibutyryl-cAMP-desensitized receptor. These data provide evidence that maximal agonist-induced desensitization of adenylate cyclase coupled β-adrenergic receptors in turkey erythrocytes occurs by a two-step mechanism

Release of overexpressed CypB activates ERK signaling through CD147 binding for hepatoma cell resistance to oxidative stress.

Science.gov (United States)

Kim, Kiyoon; Kim, Hunsung; Jeong, Kwon; Jung, Min Hyung; Hahn, Bum-Soo; Yoon, Kyung-Sik; Jin, Byung Kwan; Jahng, Geon-Ho; Kang, Insug; Ha, Joohun; Choe, Wonchae

2012-08-01

Cyclophilin, a cytosolic receptor for the immunosuppressive drug cyclosporin A, plays a role in diverse pathophysiologies along with its receptor, CD147. Although the interaction between cyclophilin A and CD147 is well established in inflammatory disease, that of cyclophilin B (CypB) with CD147 has not been fully explored, especially in cancer cell biology, and the exact molecular mechanism underlying such an association is poorly understood. In this study, we first identified high expression levels of CypB in 54 % of hepatocellular carcinoma patient tissues but in only 12.5 % of normal liver tissues. Then, we demonstrated that CypB overexpression protects human hepatoma cells against oxidative stress through its binding to CD147; this protective effect depends on the peptidyl prolyl isomerase activity of CypB. siRNA-mediated knockdown of CypB expression rendered hepatoma cells more vulnerable to ROS-mediated apoptosis. Furthermore, we also determined that a direct interaction between secreted CypB and CD147 regulates the extracellular signal-regulated kinase intracellular signaling pathway and is indispensible for the protective functions of CypB. For the first time, we demonstrated that CypB has an essential function in protecting hepatoma cells against oxidative stress through binding to CD147 and regulating the ERK pathway.

Reactivation of desensitized formyl peptide receptors by platelet activating factor: a novel receptor cross talk mechanism regulating neutrophil superoxide anion production.

Directory of Open Access Journals (Sweden)

Huamei Forsman

Full Text Available Neutrophils express different chemoattractant receptors of importance for guiding the cells from the blood stream to sites of inflammation. These receptors communicate with one another, a cross talk manifested as hierarchical, heterologous receptor desensitization. We describe a new receptor cross talk mechanism, by which desensitized formyl peptide receptors (FPRdes can be reactivated. FPR desensitization is induced through binding of specific FPR agonists and is reached after a short period of active signaling. The mechanism that transfers the receptor to a non-signaling desensitized state is not known, and a signaling pathway has so far not been described, that transfers FPRdes back to an active signaling state. The reactivation signal was generated by PAF stimulation of its receptor (PAFR and the cross talk was uni-directional. LatrunculinA, an inhibitor of actin polymerization, induced a similar reactivation of FPRdes as PAF while the phosphatase inhibitor CalyculinA inhibited reactivation, suggesting a role for the actin cytoskeleton in receptor desensitization and reactivation. The activated PAFR could, however, reactivate FPRdes also when the cytoskeleton was disrupted prior to activation. The receptor cross talk model presented prophesies that the contact on the inner leaflet of the plasma membrane that blocks signaling between the G-protein and the FPR is not a point of no return; the receptor cross-talk from the PAFRs to the FPRdes initiates an actin-independent signaling pathway that turns desensitized receptors back to a signaling state. This represents a novel mechanism for amplification of neutrophil production of reactive oxygen species.

Characterization of genetically engineered mouse hepatoma cells with inducible liver functions by overexpression of liver-enriched transcription factors.

Science.gov (United States)

Yamamoto, Hideaki; Tonello, Jane Marie; Sambuichi, Takanori; Kawabe, Yoshinori; Ito, Akira; Kamihira, Masamichi

2018-01-01

New cell sources for the research and therapy of organ failure could significantly alleviate the shortage of donor livers that are available to patients who suffer from liver disease. Liver carcinoma derived cells, or hepatoma cells, are the ideal cells for developing bioartificial liver systems. Such cancerous liver cells are easy to prepare in large quantities and can be maintained over long periods under standard culture conditions, unlike primary hepatocytes. However, hepatoma cells possess only a fraction of the functions of primary hepatocytes. In a previous study, by transducing cells with liver-enriched transcription factors that could be inducibly overexpressed-hepatocyte nuclear factor (HNF)1α, HNF1β, HNF3β [FOXA2], HNF4α, HNF6, CCAAT/enhancer binding protein (C/EBP)α, C/EBPβ and C/EBPγ-we created mouse hepatoma cells with high liver-specific gene expression called the Hepa/8F5 cell line. In the present study, we performed functional and genetic analyses to characterize the Hepa/8F5 cell line. Further, in three-dimensional cultures, the function of these cells improved significantly compared to parental cells. Ultimately, these cells might become a new resource that can be used in basic and applied hepatic research. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Case Report of Kidney Paired Donation (KPD) with Desensitization: the Strategy and Experience of 3-Way KPD in Samsung Medical Center.

Science.gov (United States)

Oh, Dongkyu; Kang, Eun Suk; Yu, Shinae; Chun, Kyoungsuk; Huh, Wooseong; Jang, Hye Ryoun; Cho, Chan Woo; Lee, Nuri; Lee, Kyo Won; Park, Hyojun; Park, Jae Berm; Kim, Sung Joo

2018-01-29

As the need for the organ donation increases, strategies to increase kidney transplantation (KT) through expanded living donation have become essential. These include kidney paired donation (KPD) programs and desensitization in incompatible transplantations. KPD enables kidney transplant candidates with incompatible living donors to join a registry with other incompatible pairs in order to find potentially compatible living donor. Positive cross match and ABO incompatible transplantation has been successfully accomplished in selective cases with several pre-conditionings. Patients who are both difficult-to-match due to broad sensitization and hard-to-desensitize because of donor conditions can often be successfully transplanted through a combination of KPD and desensitization. According to the existing data, KPD can increase the number of KTs from living donors with excellent clinical results. This is also a cost-effective treatment as compared with dialysis and desensitization protocols. We carried out 3-way KPD transplantation with one highly sensitized, positive cross match pair and with two ABO incompatible pairs. Herein we report our first successful 3-way KPD transplantation in a single center. To maximize donor-recipient matching and minimize immunologic risk, KPD programs should use proper algorithms with desensitization to identify optimal donor with simultaneous two-, three- or more complex multi-way exchanges. © 2018 The Korean Academy of Medical Sciences.

In vitro infectivity of irradiated Plasmodium berghei sporozoites to cultured hepatoma cells

International Nuclear Information System (INIS)

Sigler, C.I.; Leland, P.; Hollingdale, M.R.

1984-01-01

The invasion of gamma-irradiated Plasmodium berghei sporozoites into cultured hepatoma cells and their transformation into trophozoites was similar to invasion and transformation of non-irradiated sporozoites. However, trophozoites from irradiated sporozoites did not further develop into schizonts, but persisted within the cells for up to 3 days. Sporozoite surface protective antigen was present in trophozoites from irradiated and non-irradiated sporozoites, suggesting that hepatocyte antigen processing may contribute to the induction of anti-malarial immunity

The reduction efficacy of dentinal hypersensitivity by two commercially available desensitizing toothpastes: Vantej and Colgate Pro- Argin

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Aditya Rao

2014-01-01

Full Text Available Background : Dentin hypersensitivity is a commonly experienced problem that is triggered by an external stimulus, such as hot and cold temperature changes, pressure from tooth brushing and osmotic changes caused due to sweet or sour food and beverages. Various treatment modalities are tried and tested, amongst them desensitizing pastes have been used extensively in the past decades. Objective: The objective of these 15 days, single center, randomized clinical pilot study was to evaluate the dentin hypersensitivity reducing efficacy of two commercially available desensitizing toothpastes: One with Pro-Argin technology and the other with Novamin. Materials and Methods: Eighty subjects of dentin hypersensitivity were sampled in the present pilot study. Subjects were randomly selected and the pastes were prescribed for both the groups. Subjects were advised to brush twice daily for 2 min with the desensitizing paste and also were advised for topical application of the desensitizing paste on sensitive teeth and were asked not to rinse until morning. The evaluation was done by Air blast technique using sensitivity visual analog scale consisting of mild, moderate, and severe parameters rated on a scale of 0-10. Efficacy was compared on baseline, after 1 min of application and after 15 days. Statistical Analysis: t-test was performed and P value ≤ 0.05 was considered as statistically significant. Results: There was no statistically significant difference between the two groups after 1 min of examination, but there was a statistically significant difference in reduction of dentin hypersensitivity after 15 days interval favoring Vantej group (P ≤ 0.02. Conclusion: Desensitizing paste containing 5% NovaMin crystals provided a statistically significant reduction at 15 days interval when compared with the one containing Pro-Arginine.

Rational-Emotive Therapy versus Systematic Desensitization: A Comment on Moleski and Tosi.

Science.gov (United States)

Atkinson, Leslie

1983-01-01

Questioned the statistical analyses of the Moleski and Tosi investigation of rational-emotive therapy versus systematic desensitization. Suggested means for lowering the error rate through a more efficient experimental design. Recommended a reanalysis of the original data. (LLL)

Treatment Outcome and Maintenance in Systematic Desensitization: Professional versus Paraprofessional Effectiveness.

Science.gov (United States)

Shelton, John L.; Madrazo-Peterson, Rita

1978-01-01

Anxious students were randomly assigned to a wait-list control group; to three groups aided by experienced behavior therapists; or to three groups led by paraprofessionals. Results show paraprofessionals can achieve outcome and maintenance effects equivalent to more rigorously trained professionals. Paraprofessionals can conduct desensitization in…

Magnetic targeting of iron-oxide-labeled fluorescent hepatoma cells to the liver

International Nuclear Information System (INIS)

Luciani, Alain; Wilhelm, Claire; Gazeau, Florence; Bruneval, Patrick; Cunin, Patrick; Autret, Gwennhael; Clement, Olivier; Rahmouni, Alain

2009-01-01

The purpose of this study was to determine whether an external magnet field can induce preferential trafficking of magnetically labeled Huh7 hepatoma cells to the liver following liver cell transplantation. Huh7 hepatoma cells were labeled with anionic magnetic nanoparticles (AMNP) and tagged with a fluorescent membrane marker (PKH67). Iron-uptake was measured by magnetophoresis. Twenty C57Bl6 mice received an intrasplenic injection of 2 x 10 6 labeled cells. An external magnet (0.29 T; 25 T/m) was placed over the liver of 13 randomly selected animals (magnet group), while the remaining 7 animals served as controls. MRI (1.5 T) and confocal fluorescence microscopy (CFM) were performed 10 days post-transplantation. The presence and location of labeled cells within the livers were compared in the magnet group and controls, and confronted with histological analysis representing the standard of reference. Mean iron content per cell was 6 pg. Based on histology, labeled cells were more frequently present within recipient livers in the magnet group (p < 0.01) where their distribution was preferentially peri-vascular (p<0.05). MRI and CFM gave similar results for the overall detection of transplanted cells (kappa=0.828) and for the identification of peri-vascular cells (kappa=0.78). Application of an external magnet can modify the trafficking of transplanted cells, especially by promoting the formation of perivascular aggregates. (orig.)

Vicarious Desensitization of Test Anxiety Through Observation of Video-taped Treatment

Science.gov (United States)

Mann, Jay

1972-01-01

Procedural variations were compared for a vicarious group treatment of test anxiety involving observation of videotapes depicting systematic desensitization of a model. The theoretical implications of the present study and the feasibility of using videotaped materials to treat test anxiety and other avoidance responses in school settings are…

Treatment of Test Anxiety by Cue-Controlled Relaxation and Systematic Desensitization

Science.gov (United States)

Russell, Richard K.; And Others

1976-01-01

Test-anxious subjects (N=19) participated in an outcome study comparing systematic desensitization, cue-controlled relaxation, and no treatment. The treatment groups demonstrated significant improvement on the self-report measures of test and state anxiety but not on the behavioral indices. The potential advantages of this technique over…

Case of double cancer of the liver (hepatoma and cholangioma) caused by accumulation of thorotrast

Energy Technology Data Exchange (ETDEWEB)

Masai, K; Watanabe, T [Yanai-Byoin National Sanatorium, (Japan)

1977-03-01

Fairly many cases of delayed disorders caused by thorotrast have been reported. The authors experienced a case of a 65 year old male who had received an infusion of thorotrast solution at the old army hospital 38 years ago and died from liver cirrhosis and hepatic cancer (double cancer of hepatoma and cholangiocarcinoma). By the biopsy after his death, alpha rays were demonstrated in granules of foreign body in hepatic tissues, and in corporation with its contrast, it was certified that a chain of abnormal shadows mainly seen in the liver and the spleen, on the scout film of the abdomen before death, was caused by thorotrast. From pathological findings in hepatic cancers, hepatoma was recognized in the right lobe and cholangioma, in the left lobe, and there was no pathological relationship between the two cancers. Namely, it was double cancer within the same organ. Case of double cancer in the liver such as this case were thought to be very rare in Japan, and a few literature considerations were also reported.

Molecular dynamics study of lipid bilayers modeling the plasma membranes of mouse hepatocytes and hepatomas.

Science.gov (United States)

Andoh, Yoshimichi; Aoki, Noriyuki; Okazaki, Susumu

2016-02-28

Molecular dynamics (MD) calculations of lipid bilayers modeling the plasma membranes of normal mouse hepatocytes and hepatomas in water have been performed under physiological isothermal-isobaric conditions (310.15 K and 1 atm). The changes in the membrane properties induced by hepatic canceration were investigated and were compared with previous MD calculations included in our previous study of the changes in membrane properties induced by murine thymic canceration. The calculated model membranes for normal hepatocytes and hepatomas comprised 23 and 24 kinds of lipids, respectively. These included phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, lysophospholipids, and cholesterol. We referred to previously published experimental values for the mole fraction of the lipids adopted in the present calculations. The calculated structural and dynamic properties of the membranes such as lateral structure, order parameters, lateral self-diffusion constants, and rotational correlation times all showed that hepatic canceration causes plasma membranes to become more ordered laterally and less fluid. Interestingly, this finding contrasts with the less ordered structure and increased fluidity of plasma membranes induced by thymic canceration observed in our previous MD study.

Molecular switch of Cre/loxP for radiation modulated gene therapy on hepatoma

Energy Technology Data Exchange (ETDEWEB)

Hsieh, Y.-J. [Institute of Radiological Sciences, National Yang-Ming University, Taiwan (China); Chen, Fu-Du [Institute of Radiological Sciences, National Yang-Ming University, Taiwan (China); Institute of Radiological Sciences, Central Taiwan University of Science and Technology, Taiwan (China); Wang, F.H. [National Yang-Ming University Medical School, Taiwan (China); Ke, C.C. [National PET/Cyclotron Center, Taipei Veterans General Hospital, Taiwan (China); Wang, H.-E. [Institute of Radiological Sciences, National Yang-Ming University, Taiwan (China); Liu, R.-S. [Institute of Radiological Sciences, National Yang-Ming University, Taiwan (China) and National Yang-Ming University Medical School, Taiwan (China) and National PET/Cyclotron Center, Taipei Veterans General Hospital, Taiwan (China)]. E-mail: maimai5010@yahoo.com.tw

2007-02-01

For the purpose of enhancement of AFP promoter for the use of radiation modulated gene therapy for hepatocellular carcinoma (HCC), we combined hepatitis B virus (HBV) enhancer II with AFP promoter which shows the selectivity to the target cells to control the Cre/loxP system. Different gene constructs, pE4luc, pE4Tk, EIIAPA-Cre, E4CMV-STOP-Tk and chimeric promoters combined with HBV enhancer were constructed and transfected into HepG2, HeLa and NIH-3T3 cell lines. Cell experiments revealed that E4 enhancer responses to radiation best after 60 h irradiation at a dose range of 5-7 Gy in HepG2 stable clone. The EIIAPA promoter provided high specificity to hepatoma and activated the Cre downstream and removed the stop cassette only in hepatoma cells. After removal of the stop cassette, the E4 response to radiation could encode more Tk protein and kill more tumor cells. In summary, the chimeric EIIAPA promoter can stringently control the expression of Cre recombinase only in HCC. The radiation effect of the EIIAPA-Cre and E4CMV-STOP-Tk system shows promising results in terms of cell survival of HCC.

Molecular switch of Cre/loxP for radiation modulated gene therapy on hepatoma

International Nuclear Information System (INIS)

Hsieh, Y.-J.; Chen, Fu-Du; Wang, F.H.; Ke, C.C.; Wang, H.-E.; Liu, R.-S.

2007-01-01

For the purpose of enhancement of AFP promoter for the use of radiation modulated gene therapy for hepatocellular carcinoma (HCC), we combined hepatitis B virus (HBV) enhancer II with AFP promoter which shows the selectivity to the target cells to control the Cre/loxP system. Different gene constructs, pE4luc, pE4Tk, EIIAPA-Cre, E4CMV-STOP-Tk and chimeric promoters combined with HBV enhancer were constructed and transfected into HepG2, HeLa and NIH-3T3 cell lines. Cell experiments revealed that E4 enhancer responses to radiation best after 60 h irradiation at a dose range of 5-7 Gy in HepG2 stable clone. The EIIAPA promoter provided high specificity to hepatoma and activated the Cre downstream and removed the stop cassette only in hepatoma cells. After removal of the stop cassette, the E4 response to radiation could encode more Tk protein and kill more tumor cells. In summary, the chimeric EIIAPA promoter can stringently control the expression of Cre recombinase only in HCC. The radiation effect of the EIIAPA-Cre and E4CMV-STOP-Tk system shows promising results in terms of cell survival of HCC

Brainstem GLP-1 signalling contributes to cancer anorexia-cachexia syndrome in the rat.

Science.gov (United States)

Borner, Tito; Liberini, Claudia G; Lutz, Thomas A; Riediger, Thomas

2018-03-15

The cancer anorexia-cachexia syndrome (CACS) is a frequent and severe condition in cancer patients. Currently, no pharmacological treatment is approved for the therapy of CACS. Centrally, glucagon-like peptide-1 (GLP-1) is expressed in the nucleus tractus solitarii (NTS) and is implicated in malaise, nausea and food aversion. The NTS is reciprocally connected to brain sites implicated in the control of energy balance including the area postrema (AP), which mediates CACS in certain tumour models. Given the role of GLP-1 as a mediator of anorexia under acute sickness conditions, we hypothesized that brainstem GLP-1 signalling might play a role in the mediation of CACS. Using hepatoma tumour-bearing (TB) rats, we first tested whether the chronic delivery of the GLP-1R antagonist exendin-9 (Ex-9) into the fourth ventricle attenuates CACS. Second, we investigated whether a genetic knockdown of GLP-1 expression in the NTS ameliorates CACS. Ex-9 attenuated anorexia, body weight loss, muscle and fat depletion compared to TB controls. Similarly, TB animals with a knockdown of GLP-1 expression in the NTS had higher food intake, reduced body weight loss, and higher lean and fat mass compared to TB controls. Our study identifies brainstem GLP-1 as crucial mediator of CACS in hepatoma TB rats. The GLP-1R represents a promising target against CACS and possibly other forms of disease-related anorexia/cachexia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Desensitization of animals to the inflammatory effects of ultraviolet radiation is mediated through mechanisms which are distinct from those responsible for endotoxin tolerance

International Nuclear Information System (INIS)

Gahring, L.C.; Daynes, R.A.

1986-01-01

Desensitization to the inflammatory properties of either UVR or LPS appears to be controlled at the site of interaction between the tissues capable of producing epidermal-derived thymocyte-activating factor (ETAF)/IL 1 (epidermal keratinocytes or reticuloendothelial cells, respectively) and the exogenous inflammatory stimulus. Peritoneal macrophages obtained from LPS-desensitized mice were found to have a markedly reduced capacity to secrete ETAF/IL 1 in vitro when compared to peritoneal exudate cells (PEC) obtained from normal mice. In parallel with this decreased secretory potential by PEC was the appearance of membrane-associated IL 1 was not found to be present on PEC obtained from normal mice. Keratinocytes obtained from the skin of normal mice or keratinocytes isolated from the irradiated skin site of UVR-desensitized mice were both found to secrete high levels of ETAF/IL 1 constitutively in vitro. Furthermore, both sources of keratinocytes also expressed membrane-associated forms of ETAF/IL 1 constitutively. Therefore, unlike LPS desensitization, the phenomenon of UVR desensitization does not appear to induce changes in the ability of keratinocytes to secrete soluble forms or to express membrane forms of ETAF/IL 1. UVR desensitization may be a result of the inability of ETAF/IL 1 generated within the skin to reach the various IL 1 responsive target cells throughout the body, or may result from the impaired ability of UVR to stimulate ETAF/IL 1 production due to changes in the structure of the skin of chronically UVR-exposed animals

Bioactive chemical constituents of Curcuma longa L. rhizomes extract inhibit the growth of human hepatoma cell line (HepG2).

Science.gov (United States)

Abdel-Lateef, Ezzat; Mahmoud, Faten; Hammam, Olfat; El-Ahwany, Eman; El-Wakil, Eman; Kandil, Sherihan; Abu Taleb, Hoda; El-Sayed, Mortada; Hassenein, Hanaa

2016-09-01

The present study was designed to identify the chemical constituents of the methanolic extract of Curcuma longa L. rhizomes and their inhibitory effect on a hepatoma cell line. The methanolic extract was subjected to GC-MS analysis to identify the volatile constituents and the other part of the same extract was subjected to liquid column chromatographic separation to isolate curcumin. The inhibition of cell growth in the hepatoma cell line and the cytopathological changes were studied. GC-MS analysis showed the presence of fifty compounds in the methanolic extract of C. longa. The major compounds were ar-turmerone (20.50 %), β-sesquiphellandrene (5.20 %) and curcumenol (5.11 %). Curcumin was identified using IR, 1H and 13C NMR. The inhibition of cell growth by curcumin (IC50 = 41.69 ± 2.87 μg mL-1) was much more effective than that of methanolic extract (IC50 = 196.12 ± 5.25 μg mL-1). Degenerative and apoptotic changes were more evident in curcumin- treated hepatoma cells than in those treated with the methanol extract. Antitumor potential of the methanolic extract may be attributed to the presence of sesquiterpenes and phenolic constituents including curcumin (0.051 %, 511.39 μg g-1 dried methanol extract) in C. longa rhizomes.

Value of an hepatobiliary imaging agent for diagnosing hepatoma. Example of diethyl-IDA

Energy Technology Data Exchange (ETDEWEB)

Bourguet, P; Estable, P; Herry, J Y

1985-01-01

A comparative study was performed using two hepatic tracers, a Tc 99m labelled colloid and an hepatobiliary agent Tc 99m labelled diethyl-IDA. In some patients with isolated primary hepatocarcinoma the uptake of the hepatobiliary agent was observed but the colloid was not taken up. In the contrary, the hepatobiliary agent has proved to be of limited value for the diagnosis of hepatomas coexisting with cirrhosis and for the detection of secondary hepatocarcinoma.

Hepatitis B virus X protein promotes interleukin-7 receptor expression via NF-κB and Notch1 pathway to facilitate proliferation and migration of hepatitis B virus-related hepatoma cells

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Fanyun Kong

2016-11-01

Full Text Available Abstract Background Interleukin-7 receptor (IL-7R is involved in the abnormal function of solid tumors, but the role and regulatory mechanisms of IL-7R in HBV-related hepatocellular carcinoma (HCC are still unclear. Methods Gene and protein expression levels of IL-7R were examined in hepatoma cells transfected with hepatitis B virus (HBV plasmids and in hepatoma cells transfected with the multifunctional nonstructural protein X (HBX. The expression of HBX and IL-7R was measured by immunohistochemical analysis in HBV-related HCC tissues. The role of NF-κB and Notch1 pathways in HBX-mediated expression of IL-7R in hepatoma cells was examined. Activation of IL-7R downstream of intracellular signaling proteins AKT, JNK, STAT5, and the associated molecules CyclinD1 and matrix metalloproteinase-9 (MMP-9, was assessed in HBX-positive cells with or without treatment with IL-7R short hairpin RNA (shRNA. Additionally, the role of IL-7R in HBX-mediated proliferation and migration of hepatoma cells was investigated. Results The expression of IL-7R was increased in hepatoma cells transfected with HBV plasmids; HBX was responsible for the HBV-mediated upregulation of IL-7R. Compared to adjacent tissues, the expression of HBX and IL-7R was increased in HBV-related HCC tissues. Additionally, the relative expression levels of HBX were associated with IL-7R in HBV-related HCC tissues. The activation of NF-κB pathways and expression of Notch1 were increased in hepatoma cells transfected with HBX, and inhibition of NF-κB and Notch1 pathways significantly decreased HBX-mediated expression of IL-7R. The activation of AKT and JNK and the expression of CyclinD1 and MMP-9 were increased in HBX-positive cells. When cells were treated with IL-7R shRNA, the activation of AKT and JNK, as well as the expression of CyclinD1 and MMP-9, were significantly inhibited. Additionally, IL-7R was responsible for HBX-induced proliferation and migration ability of hepatoma cells

An evaluation of in vivo desensitization and video modeling to increase compliance with dental procedures in persons with mental retardation.

Science.gov (United States)

Conyers, Carole; Miltenberger, Raymond G; Peterson, Blake; Gubin, Amber; Jurgens, Mandy; Selders, Andrew; Dickinson, Jessica; Barenz, Rebecca

2004-01-01

Fear of dental procedures deters many individuals with mental retardation from accepting dental treatment. This study was conducted to assess the effectiveness of two procedures, in vivo desensitization and video modeling, for increasing compliance with dental procedures in participants with severe or profound mental retardation. Desensitization increased compliance for all 5 participants, whereas video modeling increased compliance for only 1 of 3 participants.

The effect of video game violence on psychological desensitization to real life violence

NARCIS (Netherlands)

Carnagey, N.L.; Anderson, C.A.; Bushman, B.J.

2007-01-01

Past research shows that violent video game exposure increases aggressive thoughts, angry feelings, physiological arousal, aggressive behaviors, and decreases helpful behaviors. However, no research has experimentally examined violent video game effects on physiological desensitization, defined as

Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative.

Science.gov (United States)

Sun, Baoguo; Meng, Jun; Xiang, Ting; Zhang, Lei; Deng, Liuxiang; Chen, Yan; Luo, Haoxuan; Yang, Zhangbin; Chen, Zexiong; Zhang, Shijun

2016-03-01

The aim of this study was to investigate the effects of the Chinese herbal formulation Jianpijiedu (JPJD) in a rat model of orthotopic hepatocellular carcinoma (OHC). The tumor-bearing rats underwent food restriction combined with laxative (FRL) treatment in order to model the nutritional and digestive symptoms of patients with hepatocellular carcinoma. In addition, the study aimed to elucidate the effect of JPJD on the T cell receptor Vβ-chain complementarity-determining region 3 (TCRVβCDR3) repertoire and the underlying mechanism. The FRL rat model was established by alternate-day food restriction and the oral administration of Glauber's salt (sodium sulfate), based on which the OHC model was then established. Subsequently, the FRL-OHC induced animals received JPJD or thymopentin-5 (TP5) for 17 days. Differences in the TCRVβCDR3 repertoire in the rat thymus, liver and hepatocellular carcinoma tissues were analyzed by polymerase chain reaction. Compared with the FRL-OHC model animals without any treatment, those treated with JPJD exhibited significantly inhibited hepatocellular carcinoma growth (PSimpsons diversity index (Ds) values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in the thymus, liver and hepatocellular carcinoma tissues. However, no anti-hepatoma effects were evident in the rats treated with TP5. In addition, TP5 increased the Ds values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in hepatocellular carcinoma tissues compared with those in the JPJD-treated group. The anti-hepatoma effects of JPJD in FRL-OHC-induced animals may be due to the promotion of the Ds values of the TCRVβCDR3 repertoire.

Treatment of Test Anxiety by Cue-Controlled Desensitization and Study-Skills Training.

Science.gov (United States)

Lent, Robert W.; Russell, Richard K.

1978-01-01

Compared relative effectiveness of two multicomponent strategies in the treatment of test anxiety. Test-anxious students were assigned to groups. Within-group changes between pre- and post-testing favored multicomponent treatments. Between groups, both desensitization treatment programs demonstrated significant improvement over no-treatment on…

Immunological mechanisms for desensitization and tolerance in food allergy1

Science.gov (United States)

Rachid, Rima; Umetsu, Dale T.

2013-01-01

Food allergy is a major public health concern in westernized countries, estimated to affect 5% of children and 3-4 % of adults. Allergen specific immunotherapy for food allergy is currently being actively evaluated, but is still experimental. The optimal protocol, in terms of the route of administration of the food, target maintenance dose, duration of maintenance therapy and the optimal patient for these procedures are still being worked out. The mechanisms underlying successful food desensitization are also unclear, in part because there is no standard immunotherapy protocol. The mechanisms involved however, may include mast cell and basophil suppression, development of food-specific IgG4 antibodies, reduction in the food specific IgE/IgG4 ratio, up-regulation and expansion of natural or inducible regulatory T cells, a skewing from a Th2 to a Th1 profile and the development of anergy and/or deletion in antigen specific cells. Additional studies are required to elucidate and understand these mechanisms by which desensitization and tolerance are achieved, and which may reveal valuable biomarkers for evaluating and following food allergic patients on immunotherapy. PMID:22821087

Pokemon Silencing Leads to Bim-Mediated Anoikis of Human Hepatoma Cell QGY7703

OpenAIRE

Liu, Kun; Liu, Feng; Zhang, Nannan; Liu, Shiying; Jiang, Yuyang

2012-01-01

Pokemon is an important proto-oncogene that plays a critical role in cellular oncogenic transformation and tumorigenesis. Anoikis, which is regulated by Bim-mediated apoptosis, is critical to cancer cell invasion and metastasis. We investigated the role of Pokemon in anoikis, and our results show that Pokemon renders liver cells resistant to anoikis via suppression of Bim transcription. We knocked-down Pokemon in human hepatoma cells QGY7703 with small interfering RNAs (siRNA). Knockdown of P...

Value of an hepatobiliary imaging agent for diagnosing hepatoma. Example of diethyl-IDA

International Nuclear Information System (INIS)

Bourguet, P.; Estable, P.; Herry, J.Y.

1985-01-01

A comparative study was performed using two hepatic tracers, a Tc 99m labelled colloid and an hepatobiliary agent Tc 99m labelled diethyl-IDA. In some patients with isolated primary hepatocarcinoma the uptake of the hepatobiliary agent was observed but the colloid was not taken up. In the contrary, the hepatobiliary agent has proved to be of limited value for the diagnosis of hepatomas coexisting with cirrhosis and for the detection of secondary hepatocarcinoma [fr

Effect of misoprostol on patients with aspirin-exacerbated respiratory disease undergoing aspirin challenge and desensitization.

Science.gov (United States)

Walters, Kristen M; Simon, Ronald A; Woessner, Katharine M; Wineinger, Nathan E; White, Andrew A

2017-07-01

Prostaglandin E 2 (PGE 2 ) is an anti-inflammatory compound that inhibits 5-lipoxygenase activity. Diminished PGE 2 regulation in aspirin-exacerbated respiratory disease (AERD) leads to respiratory reactions on cyclooxygenase 1 inhibition. In vitro studies have found that exogenous PGE 2 stabilizes inflammatory mediator release. To examine whether misoprostol (oral prostaglandin E 1 analogue) use during aspirin challenge and desensitization might decrease the severity of aspirin-induced symptoms and make desensitization safer for patients with AERD. Forty-five patients undergoing aspirin challenge and/or desensitization were randomized to misoprostol (n = 30) or placebo (n = 15) and compared with a group of historical controls (n = 31). Misoprostol (200 μg) was administered at 30 minutes, 90 minutes, and 4 hours after the first dose of nasal ketorolac. Measured end points included change in forced expiratory volume in 1 second (FEV 1 ), peak nasal inspiratory flow rate (PNIF), number of treatments received for induced reactions, and adverse gastrointestinal effects. A difference in FEV 1 and PNIF reduction was detected between misoprostol and placebo (P = .03) and misoprostol and historical controls (P = .01), respectively, during nasal ketorolac challenge. No difference was detected among aspirin reactors. Among all reactors, no difference in magnitude was found for FEV 1 (P = .13) or PNIF (P = .07) reduction across all 3 groups. Total treatment requirement was similar (P = .14). Patients receiving misoprostol were more likely to report adverse gastrointestinal effects (P = .02). The addition of misoprostol to current aspirin challenge and/or desensitization protocols reveals no protective effect in reducing the intensity of nonsteroidal anti-inflammatory drug-induced symptoms and is not recommended based on the findings in this study. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Magnetic targeting of iron-oxide-labeled fluorescent hepatoma cells to the liver

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Luciani, Alain [Universite Rene Descartes, Hopital Europeen Georges Pompidou, Laboratoire de Recherche en Imagerie, EA 4062, Paris (France); Imagerie Medicale, Faculte de Medecine Paris XII, CHU Henri Mondor, Creteil cedex (France); Wilhelm, Claire; Gazeau, Florence [Universite Paris Diderot, Batiment Condorcet, Laboratoire Matiere et Systemes Complexes, CNRS-UMR 7057, Paris Cedex (France); Bruneval, Patrick [Anatomopathologie, Hopital Europeen Georges Pompidou, Paris (France); Cunin, Patrick [Unite de Recherche Clinique, Faculte de Medecine Paris XII, CHU Henri Mondor, Creteil cedex (France); Autret, Gwennhael; Clement, Olivier [Universite Rene Descartes, Hopital Europeen Georges Pompidou, Laboratoire de Recherche en Imagerie, EA 4062, Paris (France); Rahmouni, Alain [Imagerie Medicale, Faculte de Medecine Paris XII, CHU Henri Mondor, Creteil cedex (France)

2009-05-15

The purpose of this study was to determine whether an external magnet field can induce preferential trafficking of magnetically labeled Huh7 hepatoma cells to the liver following liver cell transplantation. Huh7 hepatoma cells were labeled with anionic magnetic nanoparticles (AMNP) and tagged with a fluorescent membrane marker (PKH67). Iron-uptake was measured by magnetophoresis. Twenty C57Bl6 mice received an intrasplenic injection of 2 x 10{sup 6} labeled cells. An external magnet (0.29 T; 25 T/m) was placed over the liver of 13 randomly selected animals (magnet group), while the remaining 7 animals served as controls. MRI (1.5 T) and confocal fluorescence microscopy (CFM) were performed 10 days post-transplantation. The presence and location of labeled cells within the livers were compared in the magnet group and controls, and confronted with histological analysis representing the standard of reference. Mean iron content per cell was 6 pg. Based on histology, labeled cells were more frequently present within recipient livers in the magnet group (p < 0.01) where their distribution was preferentially peri-vascular (p<0.05). MRI and CFM gave similar results for the overall detection of transplanted cells (kappa=0.828) and for the identification of peri-vascular cells (kappa=0.78). Application of an external magnet can modify the trafficking of transplanted cells, especially by promoting the formation of perivascular aggregates. (orig.)

Professional and Subprofessional Counselors Using Group Desensitization and Insight Procedures. Final Report.

Science.gov (United States)

Neuman, Donald R.

This study compared the effects of professional and subprofessional counselors using group insight and group desensitization techniques with high and low imagery arousal test anxious college students. Two professional and two subprofessional counselors met with groups of three students for five interviews to administer insight and desensitization…

Glyco-nanoparticles with sheddable saccharide shells: A unique and potent platform for hepatoma-targeting delivery of anticancer drugs

NARCIS (Netherlands)

Chen, Wei; Zou, Yan; Meng, Fenghua; Cheng, Ru; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan

2014-01-01

Reduction-sensitive shell-sheddable glyco-nanoparticles were designed and developed based on poly(ε-caprolactone)-graft-SS-lactobionic acid (PCL-g-SS-LBA) copolymer for efficient hepatoma-targeting delivery of doxorubicin (DOX). PCL-g-SS-LBA was prepared by ring-opening copolymerization of

A case of double cancer of the liver (hepatoma and cholangioma) caused by accumulation of thorotrast

International Nuclear Information System (INIS)

Masai, Kenji; Watanabe, Tadashi

1977-01-01

Fairly many cases of delayed disorders caused by thorotrast have been reported. The authors experienced a case of 65 year old male who had received an infusion of thorotrast solution at the old army hospital 38 years ago and died for liver cirrhosis and hepatic cancer (double cancer of hepatoma and cholangiocarcinoma). By the biopsy after his death, alpha ray was proved in granules of foreign body in hepatic tissues, and in corporation with its contrast, it was certified that a chain of abnormal shadows mainly seen in the liver and the spleen, on the scout film of the abdomen before death, was caused by thorotrast. From pathological findings in hepatic cancers, hepatoma was recognized in the right lobe and cholangioma, in the left lobe, and there was no pathological relationship between two cancers. Namely, it was double cancer within the same organ. Case of double cancer in the liver such as this case was thought to be very rare in Japan, and a few literature considerations were also reported. (Tsunoda, M.)

Inhibitory effects of α-pinene on hepatoma carcinoma cell proliferation.

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Chen, Wei-Qiang; Xu, Bin; Mao, Jian-Wen; Wei, Feng-Xiang; Li, Ming; Liu, Tao; Jin, Xiao-Bao; Zhang, Li-Rong

2014-01-01

Pine needle oil from crude extract of pine needles has anti-tumor effects, but the effective component is not known. In the present study, compounds from a steam distillation extract of pine needles were isolated and characterized. Alpha-pinene was identified as an active anti-proliferative compound on hepatoma carcinoma BEL-7402 cells using the MTT assay. Further experiments showed that α-pinene inhibited BEL-7402 cells by arresting cell growth in the G2/M phase of the cell cycle, downregulating Cdc25C mRNA and protein expression, and reducing cycle dependence on kinase 1(CDK1) activity. Taken together, these findings indicate that α-pinene may be useful as a potential anti-tumor drug.

Hypersensitivity Reactions to Oxaliplatin: Identifying the Risk Factors and Judging the Efficacy of a Desensitization Protocol.

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Okayama, Tetsuya; Ishikawa, Takeshi; Sugatani, Kazuko; Yoshida, Naohisa; Kokura, Satoshi; Matsuda, Kiyomi; Tsukamoto, Shigeru; Ihara, Norihiko; Kuriu, Yoshiaki; Nakanishi, Masayoshi; Nakamura, Terukazu; Kamada, Kazuhiro; Katada, Kazuhiro; Uchiyama, Kazuhiko; Takagi, Tomohisa; Handa, Osamu; Konishi, Hideyuki; Yagi, Nobuaki; Naito, Yuji; Otsuji, Eigo; Hosoi, Hajime; Miki, Tsuneharu; Itoh, Yoshito

2015-06-01

We examined the clinical data of patients treated with oxaliplatin to determine the risk factors of oxaliplatin-related hypersensitivity reaction (HSR). In addition, we evaluated the efficacy of rechallenging patients with HSRs with oxaliplatin using prophylactic agents or desensitization procedures. This study consisted of 162 patients with colorectal cancer (88 men and 74 women) who were treated consecutively at the outpatient chemotherapy department at University Hospital, Kyoto Prefectural University of Medicine. Patients underwent chemotherapy, including oxaliplatin, between March 2006 and June 2012. We analyzed the patients' clinical backgrounds (eg, age, sex, performance status, disease stage, and allergic history) to uncover any connections to the development of HSR to oxaliplatin. In addition, we rechallenged 10 patients who had oxaliplatin-related HSR using prophylactic agents or desensitization procedures. Of 162 patients, 28 (17.2%) developed oxaliplatin-related HSRs (16, 2, 9 and 1 patient had grade 1, 2, 3, and 4 HSRs, respectively). The total cumulative dose of oxaliplatin at the onset of the HSR was 301 to 1126 mg/m(2) (median, 582 mg/m(2)), and the first reactions developed in these patients after 5 to 17 infusions of oxaliplatin (median, 8 infusions). Logistic regression analysis indicated that sex (male: odds ratio = 3.624; 95% CI, 1.181-11.122; P = 0.024) and eosinophil count in peripheral blood (odds ratio = 35.118; 95% CI, 1.058-1166.007; P = 0.046) were independent variables for oxaliplatin-related HSRs. Rechallenging patients with prophylactic agents was successful in 2 (28.6%) of 7 patients who successfully completed their treatment. On the other hand, all 3 patients rechallenged with oxaliplatin using a desensitization protocol successfully completed their treatment without new HSRs. In this retrospective study, we observed that being male and having higher counts of peripheral eosinophil could be predictors for HSR to oxaliplatin. In

Cue-Controlled Relaxation and Systematic Desensitization versus Nonspecific Factors in Treating Test Anxiety.

Science.gov (United States)

Russell, Richard K.; Lent, Robert W.

1982-01-01

Compared the efficacy of two behavioral anxiety reduction techniques against "subconscious reconditioning," an empirically derived placebo method. Examination of within-group changes showed systematic desensitization produced significant reductions in test and trait anxiety, and remaining treatments and the placebo demonstrated…

Effectiveness of Eye Movement Desensitization and Reprocessing Therapy on Public Speaking Anxiety of University Students

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Jalil Aslani

2014-08-01

Full Text Available Background: Public speaking anxiety is a prominent problem in the college student population. The purpose of this study was to determine the effectiveness of eye movement desensitization and reprocessing on public speaking anxiety of college students. Materials and Methods: The design of research was quasi-experimental with pre-post test type, and control group. The sample consistent of 30 students with speech anxiety that selected base on available sampling and assigned randomly in experimental (N=15 and control (N=15 groups. The experimental group was treated with EMDR therapy for 7 sessions. In order to collect the data, Paul’s personal report of confidence as a speaker, S-R inventory of anxiousness was used. To analyze the data, SPSS-19 software and covariance analysis were used. Results: The multivariate analysis of covariance showed that the eye movement desensitization and reprocessing reducing public speaking anxiety. The one-way analysis of covariance for each variable shows there are significant differences in confidence of speaker (p=0.001 and physiological symptoms of speech anxiety (p=0.001 at the two groups. Conclusion: These results suggest that treatment of eye movement desensitization and reprocessing is effective on reducing physiological symptoms of speech anxiety and increasing the speaker’s confidence.

Radiosensitization by inhibiting survivin in human hepatoma HepG2 cells to high-LET radiation

International Nuclear Information System (INIS)

Jin Xiaodong; Li Qiang; Wu Qingfeng; Li Ping; Gong Li; Hao Jifang; Dai Zhongying; Matsumoto, Yoshitaka; Furusawa, Yoshiya

2011-01-01

In this study, whether survivin plays a direct role in mediating high-linear energy transfer (LET) radiation resistance in human hepatoma cells was investigated. Small interfering RNA (siRNA) targeting survivin mRNA was designed and transfected into human hepatoma HepG2 cells. Real-time polymerase chain reaction (PCR) and western blotting analyses revealed that survivin expression in HepG2 cells decreased at both transcriptional and post-transcriptional levels after treatment with survivin-specific siRNA. Caspase-3 activity was determined with a microplate reader assay as well. Following exposure to high-LET carbon ions, a reduced clonogenic survival effect, increased apoptotic rates and caspase-3 activity were observed in the cells treated with the siRNA compared to those untreated with the siRNA. The cells with transfection of the survivin-specific siRNA also increased the level of G 2 /M arrest. These results suggest that survivin definitely plays a role in mediating the resistance of HepG2 cells to high-LET radiation and depressing survivin expression might be useful to improve the therapeutic efficacy of heavy ions for radioresistant solid tumors. (author)

Accelerated Desensitization with Adaptive Attitudes and Test Gains with 5th Graders

Science.gov (United States)

Miller, Melanie; Morton, Jerome; Driscoll, Richard; Davis, Kai A.

2006-01-01

The study evaluates an easily-administered test-anxiety reduction program. An entire fifth grade was screened, and 36 students identified as test-anxious were randomly assigned to an Intervention or a non-participant Control group. The intervention was an accelerated desensitization and adaptive attitudes (ADAA) treatment which involved…

Platinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study.

Science.gov (United States)

Altwerger, Gary; Gressel, Gregory M; English, Diana P; Nelson, Wendelin K; Carusillo, Nina; Silasi, Dan-Arin; Azodi, Masoud; Santin, Alessandro; Schwartz, Peter E; Ratner, Elena S

2017-01-01

The carboplatin desensitization (CD) protocol presented here allows patients with either a positive skin test or a prior hypersensitivity reaction (HSR) to safely, rapidly and effectively continue with carboplatin infusions. Newly described factors can identify patients at risk for developing adverse events during CD. A retrospective review was performed on patients with gynecologic cancer who underwent CD between 2005 and 2014. The CD protocol uses a four-step dilution process over 3.5h. 129 patients underwent CD and completed a total of 788cycles. The desensitization protocol prevented HSRs in 96% (753 out of 788) of these cycles. Patients achieved an average of 6.1cycles (SD±4.55, range 0-23) with CD. The CD protocol allowed 73% (94 of 129) of the patients to undergo carboplatin infusion without reaction. Patients with moderate to life-threatening HSRs (grade 2 through 4) were 10.5years younger at initial CD than patients with grades 0 or 1 HSRs (52.3 vs. 63, P = 0.0307). One patient death occurred during her thirteenth desensitization cycle. The HSR in this case was complicated by pre-exisiting pulmonary hypertension. This is the largest study of its kind showing a safe, effective and rapid (3.5h) CD protocol. The majority of patients with a history of either carboplatin hypersensitivity reaction or a positive skin test completed the CD protocol without HSRs. Age was identified as a risk factor for HSR severity during CD. Age can be employed along with pre-load dependent cardiac conditions as a way to help risk stratify patients undergoing CD. Copyright © 2016 Elsevier Inc. All rights reserved.

Folate-targeted paclitaxel-conjugated polymeric micelles inhibits pulmonary metastatic hepatoma in experimental murine H22 metastasis models

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Zhang Y

2014-04-01

Full Text Available Yan Zhang,1 Hui Zhang,2 Wenbin Wu,2 Fuhong Zhang,3,4 Shi Liu,3 Rui Wang,3 Yingchun Sun,1 Ti Tong,1 Xiabin Jing3 1Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, People's Republic of China; 2Department of Thoracic Surgery, Xuzhou Central Hospital, Xuzhou, Jiangsu, People's Republic of China; 3State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, People's Republic of China; 4Department of Otolaryngology, The First Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China Abstract: Hepatocellular carcinoma shows low response to most conventional chemotherapies; additionally, extrahepatic metastasis from hepatoma is considered refractory to conventional systemic chemotherapy. Target therapy is a promising strategy for advanced hepatoma; however, targeted accumulation and controlled release of therapeutic agents into the metastatic site is still a great challenge. Folic acid (FA and paclitaxel (PTX containing composite micelles (FA-M[PTX] were prepared by coassembling the FA polymer conjugate and PTX polymer conjugate. The main purpose of this study is to investigate the inhibitory efficacy of FA-M(PTX on the pulmonary metastasis of intravenously injected murine hepatoma 22 (H22 on BALB/c mice models. The lung metastatic burden of H22 were measured and tissues were analyzed by immunohistochemistry and histology (hematoxylin and eosin stain, followed by survival analysis. The results indicated that FA-M(PTX prevented pulmonary metastasis of H22, and the efficacy was stronger than pure PTX and simple PTX-conjugated micelles. In particular, the formation of lung metastasis colonies in mice was evidently inhibited, which was paralleled with the downregulated expression of matrix metalloproteinase-2 and matrix metalloproteinase-9. Furthermore, the mice bearing pulmonary metastatic hepatoma in the FA

Inducing Assertive Behavior in Chronic Schizophrenics: A Comparison of Socioenvironmental Desensitization, and Relaxation Therapies

Science.gov (United States)

Weinman, Bernard; And Others

1972-01-01

It is concluded that systematic desensitization or relaxation therapy is not effective in inducing assertive behavior in the male chronic schizophrenic. The treatment of choice for the older chronic male schizophrenic remains socioenvironmental therapy. (Author)

Panel-reactive antibody levels and renal transplantation rates in sensitized patients after desensitization and human leucocyte antigen amino acid residue matching.

Science.gov (United States)

Shang, Wenjun; Dong, Laidong; Feng, Guiwen; Wang, Yue; Pang, Xinlu; Li, Jinfeng; Liu, Lei; Zhang, Weihong

2013-08-01

To determine whether a new desensitization protocol (mycophenolate mofetil [MMF], plasmapheresis and antithymocyte globulin [ATG], complemented with human leucocyte antigen [HLA] amino acid residue matching) could reduce panel-reactive antibody (PRA) levels in sensitized patients, to facilitate successful renal transplantation. Patients awaiting transplantation with PRA levels >10% received treatment with MMF; those with PRA levels >30% were also treated with plasmapheresis. Patients whose PRA level was desensitization were eligible for transplantation. When a donor became available, traditional HLA matching and HLA amino acid residue matching were performed. All patients received ATG induction therapy postoperatively. Thirty-two sensitized patients were enrolled. Desensitization produced a significant decrease in PRA levels; 27 patients (84.4%) became eligible for transplantation and 26 (81.2%) subsequently underwent successful transplantation. Residue matching improved the proportion with a mismatch number of 0-1 from 7.7% to 65.4%, compared with traditional HLA matching. Postoperatively, all patients showed immediate graft function. Acute rejection occurred in three patients (11.5%) and infections in seven patients (25.9%); all were treated successfully. The combination of a desensitization protocol (MMF, plasmapheresis and ATG) and residue matching appears to be an effective strategy for sensitized patients awaiting renal transplantation.

INVESTIGATION OF HYPOLIPIDEMIC EFFECT OF SESQUITERPENE Γ-LACTONE AHILLIN IN HEPATOMA TISSUE CULTURE (HTC CELLS

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V. V. Ivanov

2014-01-01

Full Text Available Objective. Investigation of hypolipidemic effect of sesquiterpene γ-lactone ahillin in hepatoma tissue culture (HTC cells.Material and methods. In this study we’ve evaluated the effect of γ-lactone sesquiterpene aсhillin and gemfibrozil (comparator drug on the lipid content in the hepatoma tissue culture (HTC cell which were incubated with a fat emulsion lipofundin by fluorescent method with vital dye Nile Redand staining the cells with the dye Oil Red O. The cell viability was investigated using the MTT-test and staining with Trypan blue.Results. Cultivation cells HTC with aсhillin and gemfibrozilat concentrations ranging from 0.5 to1.5 mM and from0.25 mM to0.5 mM, respectively, resulted in dose-dependent decrease of the fluorescence’s intensity Nile Red. It reflects a decrease in lipid content in the cells. At these concentrations the drugs didn’t have cytotoxic effect and the cell viability didn’t change compared to the control culture.An experimental hyperlipidemia in the hepatoma culture cells was induced by adding to the incubation medium a fat emulsion lipofundin at a final concentration 0.05%. The intensity of fluorescence Nile Red in the cells was increased 4 fold (p < 0.05. This result suggests the significant accumulation of lipids in the cell’s cytosol and confirmed by microscopy after staining neutral lipids with the dye Oil Red O. Under these conditions aсhillin and gemfibrozil reduced lipid content in cells and hadthe effect at concentrations of0.5 mM and0.25 mM respectively.Conclusion. In the lipofundin-mediated model of hyperlipidemia the sesquiterpene lactone aсhillin prevents the lipid accumulation in cells. It confirms by decrease of fluorescence Nile Red and reduction lipid drops which were stained with Oil Red O in cytosol. To establish the molecular targets of aсhillin’saction on lipid metabolism in cell culture HTC we need to investigate a gene expression of key enzymes of lipid metabolism.

Trans-generational desensitization and within-generational resensitization of a sucrose-best neuron in the polyphagous herbivore Helicoverpa armigera (Lepidoptera: Noctuidae).

Science.gov (United States)

Ma, Ying; Li, Jingjing; Tang, Qingbo; Zhang, Xuening; Zhao, Xincheng; Yan, Fengming; van Loon, Joop J A

2016-12-14

Dietary exposure of insects to a feeding deterrent substance for hours to days can induce habituation and concomitant desensitization of the response of peripheral gustatory neurons to such a substance. In the present study, larvae of the herbivore Helicoverpa armigera were fed on diets containing either a high, medium or low concentration of sucrose, a major feeding stimulant. The responsiveness of the sucrose-best neuron in the lateral sensilla styloconica on the galea was quantified. Results showed the response of the sucrose-best neuron exposed to high-sucrose diets decreased gradually over successive generations, resulting in complete desensitization in the 5 th and subsequent generations. However, the sensitivity was completely restored in the ninth generation after neonate larvae were exposed to low-sucrose diet. These findings demonstrate phenotypic plasticity and exclude inadvertent artificial selection for low sensitivity to sucrose. No significant changes were found in the sensitivity of caterpillars which experienced low- or medium-sucrose diets over the same generations. Such desensitization versus re-sensitization did not generalise to the phagosimulant myo-inositol-sensitive neuron or the feeding deterrent-sensitive neuron. Our results demonstrate that under conditions of high sucrose availability trans-generational desensitization of a neuron sensitive to this feeding stimulant becomes more pronounced whereas re-sensitization occurs within one generation.

On the ligand binding profile and desensitization of plant ionotropic glutamate receptor (iGluR)-like channels functioning in MAMP-triggered Ca2+ influx

DEFF Research Database (Denmark)

Kwaaitaal, Mark Adrianus Cornelis J; Maintz, Jens; Cavdar, Meltem

2012-01-01

in the putative agonist binding profile and potential mode of desensitization of MAMP-activated plant iGluRs. Based on results from pharmacological inhibition and desensitization experiments, we propose that plant iGluR complexes responsible for the MAMP-triggered Ca ( 2+) signature have a binding profile...... that combines the specificities of mammalian NMDA-and non-NMDA types of iGluRs, possibly reflecting the evolutionary history of plant and animal iGluRs. We further hypothesize that, analogous to the mammalian NMDA-NR1 receptor, desensitization of plant iGluR-like channels might involve binding of the ubiquitous...

The Eye Movement Desensitization and Reprocessing Procedure Prevents Defensive Processing in Health Persuasion

NARCIS (Netherlands)

Dijkstra, Arie; van Asten, Regine

2014-01-01

In the present study, the method of eye movement desensitization and reprocessing (EMDR) is studied to understand and prevent defensive reactions with regard to a negatively framed message advocating fruit and vegetable consumption. EMDR has been shown to tax the working memory. Participants from a

A Self-Control Versus a Counterconditioning Paradigm for Systematic Desensitization: An Experimental Comparison

Science.gov (United States)

Spiegler, Michael D.; And Others

1976-01-01

A comparison was made between the traditional counterconditioning paradigm and a self-control paradigm of systematic desensitization. College students reporting high test anxiety and indicating interest in receiving treatment were assigned to counterconditioning, self-control, or wait-list control conditions. As predicted, self-control procedures…

Desensitization and Modeling Treatments of Spider Fear Using Two Types of Scenes

Science.gov (United States)

Denney, Douglas R.; Sullivan, Bernard J.

1976-01-01

Three types of therapy were combined with two types of scenes. Spider-phobic subjects were assigned to one of the six treatment conditions or to an untreated control group. In general, (a) Desensitization and modeling therapies were equally effective; (b) modeling alone was more effective than mere exposure to the phobic object. (Author)

Hepatoscintiangiography of normal liver and its alteration in hepatomas and liver abscess

International Nuclear Information System (INIS)

Bahk, Y.W.; Chung, S.K.

1984-01-01

This study was performed to establish normal hepatoscintiangiographic (HSA) pattern of hepatic blood flow and to investigate differential HSA findings of primary and metastatic carcinomas and abscess of the liver. HSA was carried out after intravenous bolus injection of l0 mCi of Tc-99m-phytate by obtaining sequential anterior images of 1-second exposure for 16 seconds. Observations included (1) baseline study of normal hepatic blood flow patterns by correlating with contrast angiogram, (2) time-sequence phasing of normal HSA, and (3) analysis of altered patterns in primary and metastatic carcinomas and abscess of the liver. Results were: (1) Normal HSA demonstrated 3 distinct phases of arterialization (AP), arterial hepatrogram (AHP), and portal venous hepatogram (PVHP). The means of each phase were 5.3, 6.3, and 8.3 seconds, respectively. Portal vein could be seen in all but one of 20 normal subjects. (2) Pattern changes in disease groups were early start of AP in carcinomas and very early start of AP in abscess. AP became prolonged in all disease groups. (3) Distinction between AHP and PVHP was sharp in metastasis and abscess but was unsharp in primary hepatoma. Cold area or areas became vascularized in primary hepatoma but not in abscess. Cold areas of metastasis were inhomogenously vascularized in late AP and throughout AHP and became relatively avascular as PVHP began. The cold area of abscess showed rim enhancement during AH and APH. These differences in HSA pattern were very useful in differential diagnosis of the diseases studied

Gene therapy of cancer and development of therapeutic target gene

Energy Technology Data Exchange (ETDEWEB)

Kim, Chang Min; Kwon, Hee Chung

1998-04-01

We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.

Gene therapy of cancer and development of therapeutic target gene

International Nuclear Information System (INIS)

Kim, Chang Min; Kwon, Hee Chung

1998-04-01

We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene

Effectiveness of cognitive behavioral therapy integrated with systematic desensitization, cognitive behavioral therapy combined with eye movement desensitization and reprocess­ing therapy, and cognitive behavioral therapy combined with virtual reality exposure therapy methods in the treatment of flight anxiety: a randomized trial

Directory of Open Access Journals (Sweden)

Triscari MT

2015-10-01

Full Text Available Maria Teresa Triscari,1 Palmira Faraci,2 Dario Catalisano,3 Valerio D’Angelo,1 Viviana Urso1 1Laboratory for Psychosomatic Disorders, Local Health Trust, Palermo, Italy; 2Faculty of Human and Social Sciences, University of Enna “Kore”, Enna, Italy; 3Italian Flight Safety Committee, Aeroporto di Fiumicino, Fiumicino (RM, Italy Abstract: The purpose of the research was to compare the effectiveness of the following treatment methods for fear of flying: cognitive behavioral therapy (CBT integrated with systematic desensitization, CBT combined with eye movement desensitization and reprocessing therapy, and CBT combined with virtual reality exposure therapy. Overall, our findings have proven the efficacy of all interventions in reducing fear of flying in a pre- to post-treatment comparison. All groups showed a decrease in flight anxiety, suggesting the efficiency of all three treatments in reducing self-report measures of fear of flying. In particular, our results indicated significant improvements for the treated patients using all the treatment programs, as shown not only by test scores but also by participation in the post-treatment flight. Nevertheless, outcome measures maintained a significant effect at a 1-year follow-up. In conclusion, combining CBT with both the application of eye movement desensitization and reprocessing treatment and the virtual stimuli used to expose patients with aerophobia seemed as efficient as traditional cognitive behavioral treatments integrated with systematic desensitization. Keywords: flight anxiety, fear of flying, aerophobia, cognitive behavioral therapy, EMDR, VRET 

Kinetic imaging of NPC1L1 and sterol trafficking between plasma membrane and recycling endosomes in hepatoma cells

DEFF Research Database (Denmark)

Hartwig Petersen, Nicole; Færgeman, Nils J; Yu, Liqing

2008-01-01

fluorescent protein (NPC1L1-EGFP) and cholesterol analogues in hepatoma cells. At steady state about 42% of NPC1L1 resided in the transferrin (Tf) positive, sterol enriched endocytic recycling compartment (ERC), while time-lapse microscopy demonstrated NPC1L1 traffic between plasma membrane and ERC...... the ERC to the plasma membrane. NPC1L1-EGFP facilitated transport of fluorescent sterols from the plasma membrane to the ERC. Insulin induced translocation of vesicles containing NPC1L1 and fluorescent sterol from the ERC to the cell membrane. Upon polarization of hepatoma cells NPC1L1 resided almost...... exclusively in the canalicular membrane, where the protein is highly mobile. Our study demonstrates dynamic trafficking of NPC1L1 between cell surface and intracellular compartments and suggests that this transport is involved in NPC1L1 mediated cellular sterol uptake....

Chylomicron remnant-vitamin A metabolism by the human hepatoma cell line HepG2

International Nuclear Information System (INIS)

Lenich, C.M.

1985-01-01

The binding and metabolism of [ 3 H] vitamin A-containing chylomicron remnants (CMR) by the human hepatoma cell line Hep G2 was studied. Mesenteric lymph chylomicrons (CM) were collected from [ 3 H] retinol-fed rats and incubated with lipoprotein-lipase to obtain CMR. At 4 0 C, specific CMR binding was inhibited by excess unlabeled CMR. Specific binding predominated at low concentrations and approached saturation while total binding continued to increase over an extensive concentration range (0.45-32 μg triglyceride/ml). CMR uptake at 37 0 C was greater than that of CM and at least 100 times more efficient than the fluid-phase pinocytosis of sucrose. CMR binding increased as the extent of lipolysis obtained by incubation with lipoprotein-lipase increased. Addition of human apolipoprotein E enhanced both CMR and CM binding. After internalization, Hep G2 cells hydrolyzed CMR-[ 3 H]retinyl esters and radiolabeled metabolites accumulated as a function of time and temperature. As a function of the concentration of [ 3 H] VA initially cell-bound, retinol and retinyl esters accumulated as the major cell-associated metabolites. By contrast, retinol was the major metabolite in the medium only at low VA concentrations as other more polar metabolites accumulated at higher concentrations (> 110 pmol VA/mg cell protein). The accumulation of CMR-VA metabolites in the medium was reduced when cells were preincubated in retinol-supplemented media. Also, the specific activity of retinol in the medium closely resembled that in the cell indicating that CMR-VA mixed with the cellular store prior to its secretion

Desensitization to darunavir in a pediatric patient

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Julio César Cambray-Gutiérrez

2015-07-01

Full Text Available Treatment of HIV infection requires the combination of multiple antiretroviral drugs, known as highly active antiretroviral therapy (HAART; however, up to 84% of patients experience adverse drug effects that lead to discontinuation within first months of treatment. Skin manifestations are reported to 22% of patients. The severity of these is variable, such as erythema multiforme, rash, hives and severe skin reactions at less than 2%. Mild rashes, usually transient and self-limiting, while severe reactions require immediately remove the drug involved to prevent progression of the reaction. Only in those cases where the offending drug does not have another alternative and documented the reaction is mediated type I hypersensitivity mechanisms, can be performed desensitization protocol.

Effect of a Desensitizing Varnish on Microleakage of Two Self-Etch Adhesives

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Anna Saffarpour

2016-08-01

Full Text Available Objectives: The aim of this in-vitro experimental study was to assess the effect of application of a desensitizing varnish on the enamel and dentin marginal seal.Materials and Methods: Seventy-two freshly extracted, intact human premolar teeth were divided into four groups (n=18. Class V cavities (3mm in length, 2mm in width and 2mm in depth were prepared on the buccal surface of each tooth. The following sealing materials were applied in the four groups: One-step Clearfil S3 Bond (S3 self-etch adhesive, two-step Clearfil SE Bond (SE self-etch adhesive, S3 Bond+ VivaSens desensitizing varnish (VS+S3 and Clearfil SE Bond + VivaSens (VS+SE. The cavities on the teeth were then incrementally filled with Z350 light-cure composite. The teeth were stored in distilled water for 24 hours at 37°C, and were then thermocycled for 1000 cycles. Then, all the specimens were prepared for dye penetration test and were immersed in 2% basic fuchsin dye and incubated at 37°C for 24 hours. The teeth were then sectioned buccolingually along the center of restorations with a diamond disk.   Microleakage at the tooth-restoration interface was assessed in the enamel and dentin margins blindly using dye penetration under a stereomicroscope at ×20 magnification.Results: There was significantly greater leakage at the enamel and dentin margins in group VS+SE than in group SE; also, these values were higher in group VS+S3 than in S3.Conclusion: Combined application of desensitizing varnish and self-etch adhesives seems to increase microleakage in composite restorations. Thus, its application is not suggested.

Renal transplantation across the donor-specific antibody barrier: Graft outcome and cancer risk after desensitization therapy

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Ching-Yao Yang

2016-06-01

Conclusion: When compared to renal transplantation without DSA, desensitization therapy for DSA resulted in equivalent renal transplant outcome but potentially increased risk of urothelial carcinoma after transplantation.

The interaction of HAb18G/CD147 with integrin α6β1 and its implications for the invasion potential of human hepatoma cells

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Tang Juan

2009-09-01

Full Text Available Abstract Background HAb18G/CD147 plays pivotal roles in invasion by hepatoma cells, but the underlying mechanism remains unclear. Our previous study demonstrated that overexpression of HAb18G/CD147 promotes invasion by interacting with integrin α3β1. However, it has never been investigated whether α3β1 is solely responsible for this process or if other integrin family members also interact with HAb18G/CD147 in human hepatoma cells. Methods Human SMMC-7721 and FHCC98 cells were cultured and transfected with siRNA fragments against HAb18G/CD147. The expression levels of HAb18G/CD147 and integrin α6β1 were determined by immunofluorescent double-staining and confocal imaging analysis. Co-immunoprecipitation and Western blot analyses were performed to examine the native conformations of HAb18G/CD147 and integrin α6β1. Invasion potential was evaluated with an invasion assay and gelatin zymography. Results We found that integrin α6β1 co-localizes and interacts with HAb18G/CD147 in human hepatoma cells. The enhancing effects of HAb18G/CD147 on invasion capacity and secretion of matrix metalloproteinases (MMPs were partially blocked by integrin α6β1 antibodies (P 2+ mobilization, significantly reduced cell invasion potential and secretion of MMPs in human hepatoma cells (P Conclusion These results suggest that α6β1 interacts with HAb18G/CD147 to mediate tumor invasion and metastatic processes through the PI3K pathway.

Carboplatin Hypersensitivity Reactions in Pediatric Low Grade Glioma Are Protocol Specific and Desensitization Shows Poor Efficacy.

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Dodgshun, Andrew J; Hansford, Jordan R; Cole, Theresa; Choo, Sharon; Sullivan, Michael J

2016-01-01

The use of carboplatin for the treatment of pediatric low grade gliomas (PLGG) is often limited by the development of carboplatin hypersensitivity. Reported rates of carboplatin hypersensitivity reactions vary between 6% and 32% in these patients. Here we report the frequency of carboplatin hypersensitivity reactions depending on the treatment regimen used, and outcomes of carboplatin desensitization. The records of all patients in a single institution who were treated with carboplatin for PLGG were accessed and all patients receiving more than one dose of carboplatin are reported. Thirty four patients with PLGG were treated with carboplatin according to one of the two different regimens. Carboplatin hypersensitivity was documented in 47% of patients, but the frequency differed by treatment protocol. Those patients treated with 4-weekly single agent carboplatin had carboplatin allergy in 8% of cases whereas 68% of those treated with combined carboplatin and vincristine (every three weeks, according to the SIOP 2004 low grade glioma protocol) had carboplatin reactions (OR 23.6, P Desensitization was only successful in two out of 10 patients in whom it was attempted. Hypersensitivity reactions to carboplatin are more common in this cohort than previously reported and rates are protocol-dependent. Desensitization showed limited effectiveness in this cohort. © 2015 Wiley Periodicals, Inc.

Role of ROS-mediated autophagy in radiation-induced bystander effect of hepatoma cells.

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Wang, Xiangdong; Zhang, Jianghong; Fu, Jiamei; Wang, Juan; Ye, Shuang; Liu, Weili; Shao, Chunlin

2015-05-01

Autophagy plays a crucial role in cellular response to ionizing radiation, but it is unclear whether autophagy can modulate radiation-induced bystander effect (RIBE). Here, we investigated the relationship between bystander damage and autophagy in human hepatoma cells of HepG2. HepG2 cells were treated with conditioned medium (CM) collected from 3 Gy γ-rays irradiated hepatoma HepG2 cells for 4, 12, or 24 h, followed by the measurement of micronuclei (MN), intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and protein expressions of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 in the bystander HepG2 cells. In some experiments, the bystander HepG2 cells were respectively transfected with LC3 small interfering RNA (siRNA), Beclin-1 siRNA or treated with 1% dimethyl sulfoxide (DMSO). Additional MN and mitochondrial dysfunction coupled with ROS were induced in the bystander cells. The expressions of protein markers of autophagy, LC3-II/LC3-I and Beclin-1, increased in the bystander cells. The inductions of bystander MN and overexpressions of LC3 and Beclin-1 were significantly diminished by DMSO. However, when the bystander cells were transfected with LC3 siRNA or Beclin-1 siRNA, the yield of bystander MN was significantly enhanced. The elevated ROS have bi-functions in balancing the bystander effects. One is to cause MN and the other is to induce protective autophagy.

Effects of exogenous cyclic AMP on growth characteristics and radiation response of Reuber H35 hepatoma cells

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van Rijn, J.; van Den Berg, J.; van Meeteren, A.; van Wijk, R.

1983-01-01

Reuber H35 rat hepatoma cells, clone KRC, were used to study the effect of cyclic AMP on radiation-induced cell death. Treatment of logarithmically growing cultures with 0.5 mM cAMP for 17 hr prior to irradiation resulted in a decreased cell survival. Similar results were obtained with cultures irradiated after treatment with Bt 2 cAMP. Treatment of H35 cells with cAMP or Bt 2 cAMP caused inhibition of their proliferation and resulted in an accumulation of cells in early S phase and depletion of G2-phase cells. In synchronized cultures cells were relatively radioresistant during their S phase. In addition to single-dose treatment with X rays, the effect of Bt 2 cAMP on radiation-induced cell death was studied during fractionated irradiation wtih 2.5 Gy per day. This fractionated irradiation resulted in a dose-reduction factor of 1.6 at the 10% survival level and a 10-fold decrease in the surviving cell population due to the cooperative effects of Bt 2 cAMP on growth rate and radiation survival. The effect of cAMP on radiation-induced mitotic delay was also studied. It appeared that where cAMP had on effect on the progression of G2 cells into mitosis, it prevented cells from recovery from the X-ray mitotic delay in G2

Retroviral-mediated gene transfer of human phenylalanine hydroxylase into NIH 3T3 and hepatoma cells

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Ledley, F.D.; Grenett, H.E.; McGinnis-Shelnutt, M.; Woo, S.L.C.

1986-01-01

Phenylketonuria (PKU) is caused by deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). A full-length human PAH cDNA sequence has been inserted into pzip-neoSV(X), which is a retroviral vector containing the bacterial neo gene. The recombinant has been transfected into Psi2 cells, which provide synthesis of the retroviral capsid. Recombinant virus was detected in the culture medium of the transfected Psi2 cells, which is capable of transmitting the human PAH gene into mouse NIH 3T3 cells by infection leading to stable incorporation of the recombinant provirus. Infected cells express PAH mRNA, immunoreactive PAH protein, and exhibit pterin-dependent phenylaline hydroxylase activity. The recombinant virus is also capable of infecting a mouse hepatoma cell line that does not normal synthesize PAH. PAH activity is present in the cellular extracts and the entire hydroxylation system is reconstituted in the hepatoma cells infected with the recombinant viruses. Thus, recombinant viruses containing human PAH cDNA provide a means for introducing functional PAH into mammalian cells of hepatic origin and can potentially be introduced into whole animals as a model for somatic gene therapy for PKU.

Mechanism(s of Toxic Action of Zn2+ and Selenite: A Study on AS-30D Hepatoma Cells and Isolated Mitochondria

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Elena A. Belyaeva

2011-01-01

Full Text Available Mitochondria of AS-30D rat ascites hepatoma cells are found to be the main target for Zn2+ and sodium selenite (Na2SeO3. High [mu]M concentrations of Zn2+ or selenite were strongly cytotoxic, killing the AS-30D cells by both apoptotic and necrotic ways. Both Zn2+ and selenite produced strong changes in intracellular generation of reactive oxygen species (ROS and the mitochondrial dysfunction via the mitochondrial electron transport chain (mtETC disturbance, the membrane potential dissipation, and the mitochondrial permeability transition pore opening. The significant distinctions in toxic action of Zn2+ and selenite on AS-30D cells were found. Selenite induced a much higher intracellular ROS level (the early event compared to Zn2+ but a lower membrane potential loss and a lower decrease of the uncoupled respiration rate of the cells, whereas the mtETC disturbance was the early and critical event in the mechanism of Zn2+ cytotoxicity. Sequences of events manifested in the mitochondrial dysfunction produced by the metal/metalloid under test are compared with those obtained earlier for Cd2+, Hg2+, and Cu2+ on the same model system.

Effects of Uptake of Hydroxyapatite Nanoparticles into Hepatoma Cells on Cell Adhesion and Proliferation

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Meizhen Yin

2014-01-01

Full Text Available Hydroxyapatite nanoparticles (nano-HAPs were prepared by homogeneous precipitation, and size distribution and morphology of these nanoparticles were determined by laser particle analysis and transmission electron microscopy, respectively. Nano-HAPs were uniformly distributed, with rod-like shapes sizes ranging from 44.6 to 86.8 nm. Attached overnight, suspended, and proliferating Bel-7402 cells were repeatedly incubated with nano-HAPs. Inverted microscopy, transmission electron microscopy, and fluorescence microscopy were used to observe the cell adhesion and growth, the culture medium containing nano-HAPs, the cell ultrastructure, and intracellular Ca2+ labeled with a fluo-3 calcium fluorescent probe. The results showed that nano-HAPs inhibited proliferation of Bel-7402 cells and, caused an obvious increase in the concentration of intracellular Ca2+, along with significant changes in the cell ultrastructure. Moreover, nano-HAPs led suspended cells and proliferating cells after trypsinized that did not attach to the bottom of the culture bottle died. Nano-HAPs continuously entered these cells. Attached, suspended, and proliferating cells endocytosed nano-HAPs, and nanoparticle-filled vesicles were in the cytoplasm. Therefore, hepatoma cellular uptake of nano-HAPs through endocytosis was very active and occurred continuously. Nano-HAPs affected proliferation and adhesion of hepatoma cells probably because uptake of nano-HAPs blocked integrin-mediated cell adhesion, which may have potential significance in inhibiting metastatic cancer cells to their target organ.

The Retentive Strength of Cemented Zirconium Oxide Crowns after Dentin Pretreatment with Desensitizing Paste Containing 8% Arginine and Calcium Carbonate

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Pilo, Raphael; Harel, Noga; Nissan, Joseph; Levartovsky, Shifra

2016-01-01

The effect of dentin pretreatment with Desensitizing Paste containing 8% arginine and calcium carbonate on the retention of zirconium oxide (Y-TZP) crowns was tested. Forty molar teeth were mounted and prepared using a standardized protocol. Y-TZP crowns were produced using computer-aided design and computer-aided manufacturing (CAD-CAM) technology. The 40 prepared teeth were either pretreated with Desensitizing Paste or not pretreated. After two weeks, each group was subdivided into two groups, cemented with either Resin Modified Glass Ionomer Cement (RMGIC) or Self Adhesive Resin Cement (SARC)). Prior to cementation, the surface areas of the prepared teeth were measured. After aging, the cemented crown-tooth assemblies were tested for retentive strength using a universal testing machine. The debonded surfaces of the teeth and crowns were examined microscopically at 10× magnification. Pretreating the dentin surfaces with Desensitizing Paste prior to cementation did not affect the retention of the Y-TZP crowns. The retentive values for RMGIC (3.04 ± 0.77 MPa) were significantly higher than those for SARC (2.28 ± 0.58 MPa). The predominant failure modes for the RMGIC and SARC were adhesive cement-dentin and adhesive cement-crown, respectively. An 8.0% arginine and calcium carbonate in-office desensitizing paste can be safely used to reduce post-cementation sensitivity without reducing the retentive strength of Y-TZP crowns. PMID:27023532

The Retentive Strength of Cemented Zirconium Oxide Crowns after Dentin Pretreatment with Desensitizing Paste Containing 8% Arginine and Calcium Carbonate

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Raphael Pilo

2016-03-01

Full Text Available The effect of dentin pretreatment with Desensitizing Paste containing 8% arginine and calcium carbonate on the retention of zirconium oxide (Y-TZP crowns was tested. Forty molar teeth were mounted and prepared using a standardized protocol. Y-TZP crowns were produced using computer-aided design and computer-aided manufacturing (CAD-CAM technology. The 40 prepared teeth were either pretreated with Desensitizing Paste or not pretreated. After two weeks, each group was subdivided into two groups, cemented with either Resin Modified Glass Ionomer Cement (RMGIC or Self Adhesive Resin Cement (SARC. Prior to cementation, the surface areas of the prepared teeth were measured. After aging, the cemented crown-tooth assemblies were tested for retentive strength using a universal testing machine. The debonded surfaces of the teeth and crowns were examined microscopically at 10× magnification. Pretreating the dentin surfaces with Desensitizing Paste prior to cementation did not affect the retention of the Y-TZP crowns. The retentive values for RMGIC (3.04 ± 0.77 MPa were significantly higher than those for SARC (2.28 ± 0.58 MPa. The predominant failure modes for the RMGIC and SARC were adhesive cement-dentin and adhesive cement-crown, respectively. An 8.0% arginine and calcium carbonate in-office desensitizing paste can be safely used to reduce post-cementation sensitivity without reducing the retentive strength of Y-TZP crowns.

Outcomes Following ABO-Incompatible Kidney Transplantation Performed After Desensitization by Nonantigen-Specific Immunoadsorption.

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Becker, Luis E; Siebert, Daniela; Süsal, Caner; Opelz, Gerhard; Leo, Albrecht; Waldherr, Rüdiger; Macher-Goeppinger, Stephan; Schemmer, Peter; Schaefer, Sebastian Markus; Klein, Katrin; Beimler, Jörg; Zeier, Martin; Schwenger, Vedat; Morath, Christian

2015-11-01

For desensitization of ABO-incompatible kidney transplant recipients we recently proposed nonantigen-specific immunoadsorption (IA) and rituximab. We now compared clinical outcomes of 34 ABO-incompatible living-donor kidney recipients who were transplanted using this protocol with that of 68 matched ABO-compatible patients. In addition, we analyzed efficacy and cost of nonantigen-specific as compared to blood group antigen-specific IA. Before desensitization, the median isoagglutinin titer of 34 ABO-incompatible patients was 1:64 (Coombs technique). Patients received a median of 7 preoperative IA treatments. Twenty-four patients had a median of 2 additional plasmapheresis treatments to reach the preoperative target isoagglutinin titer of 1:8 or less. After a median postoperative follow-up of 22 months, overall graft survival in the ABO-incompatible group was not significantly different from that in ABO-compatible patients (log-rank P = 0.20), whereas patient survival tended to be lower (log-rank P = 0.05). The incidence of rejection episodes was 15% in both groups. The ABO-incompatible kidney recipients had a higher incidence of BK virus replication (P = 0.04) and nephropathy (P = 0.01) and showed more often colonization with multidrug resistant bacteria (P = 0.02). In comparison to blood group antigen-specific IA, nonantigen-specific IA showed equal efficacy but was associated with reduction in cost. Clinical outcomes of ABO-incompatible patients desensitized with a nonantigen-specific IA device and rituximab do not differ from that of matched ABO-compatible patients although a trend toward reduced patient survival was noted. Special attention must be paid to the higher incidence of BK virus infection in recipients of ABO-incompatible grafts.

A study on the thermochemotherapy effect of nanosized As2O3/MZF thermosensitive magnetoliposomes on experimental hepatoma in vitro and in vivo

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Wang, Li; Zhang, Jia; An, Yanli; Wang, Ziyu; Liu, Jing; Li, Yutao; Zhang, Dongsheng

2011-08-01

In this paper, we describe the synthesis and characterization of a nanosized, thermosensitive magnetoliposome encapsulating magnetic nanoparticles (MZFs) and antitumor drugs (As2O3). The nanoliposomes were spherical and mostly single volume, with an average diameter of 128.2 nm. Differential scanning calorimetry (DSC) showed a liposome phase transition temperature of 42.71 °C. After that, we studied the liposomes' anti-hepatoma effect in vitro and in vivo. The antitumor effect of the nanoliposomes on human hepatoma cells, SMMC-7721, and changes in expression of apoptosis-related proteins were examined in vitro. The results show that As2O3/MZF thermosensitive magnetoliposomes combined with hyperthermia had a great impact on the Bax/Bcl-2 ratio, which increased to 1.914 and exhibited a rapid response to induce apoptosis of tumor cells. An in situ rabbit liver tumor model was established and used to evaluate the antitumor effect of combined hyperthermia and chemotherapy following transcatheter arterial embolization with As2O3/MZF thermosensitive magnetoliposomes. The results demonstrated a strong anti-hepatoma effect, with a tumor volume inhibition rate of up to 85.22%. Thus, As2O3/MZF thermosensitive magnetoliposomes may play a great role in the treatment of hepatocarcinoma.

Oral desensitization in children with immunoglobulin E-mediated cow's milk allergy--follow-up at 4 yr and 8 months.

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Meglio, Paolo; Giampietro, Paolo G; Gianni, Simona; Galli, Elena

2008-08-01

Until now, the basic treatment for food allergy has been to avoid the offending item. This approach is difficult in the case of common foods and in the case where there is a risk of severe reaction after consuming the offending food, even inadvertently. This is the follow-up of a previous study aimed at desensitizing 21 children with immunoglobulin E (IgE)-mediated cow's milk (CM) allergy. This protocol was totally or partially successful in 85% of cases, but failed in the remaining 15%. Our aims were to study the long-term effectiveness and safety of oral CM desensitization, and the prognostic value of Skin Prick Test (SPT) and specific serum CM IgE. The 21 children were called back (one dropped out). The allergic history and other information on CM intake over the last 4-5 yr were recorded. Children underwent SPT, and end-point SPT, with casein and alpha-lactoalbumin. Specific CM IgE was also measured. At follow-up, 14/20 children totally (n = 13, 65%) or partially (n = 1, 5%) tolerated CM. None of the recalled children reported use of emergency care. SPT positivity to casein and/or alpha-lactoalbumin decreased significantly (p < 0.01), and all the negative SPT referred to the tolerant children. Cutaneous sensitivity to both casein and alpha-lactoalbumin (end-point SPT) significantly decreased after the 6-month desensitization period of the previous study (p < 0.001), but did not decrease significantly at follow-up. A significant reduction of serum-specific CM IgE was also observed (p < 0.05). Clinical tolerance induced by oral CM desensitization persists in time. Negativization of SPT and reduction of specific CM IgE could be considered prognostic indicators of CM tolerance. Oral CM desensitization seems to be a promising method to treat CM food allergy. This protocol is time-consuming but offers the advantage that it can be performed at home. This methodology must only be used by trained staff.

Cyclic Mechanical Stretch Up-regulates Hepatoma-Derived Growth Factor Expression in Cultured Rat Aortic Smooth Muscle Cells.

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Kao, Ying-Hsien; Chen, Po-Han; Sun, Cheuk-Kwan; Chang, Yo-Chen; Lin, Yu-Chun; Tsai, Ming-Shian; Lee, Po-Huang; Cheng, Cheng-I

2018-02-21

Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. This study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uni-axial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 hours of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and PCNA, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced TNF-a, whereas RhoA/ROCK inhibition significantly blunted the IL-6 production and HDGF over-expression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration. ©2018 The Author(s).

Accelerated Desensitization and Adaptive Attitudes Interventions and Test Gains with Academic Probation Students

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Driscoll, Richard; Holt, Bruce; Hunter, Lori

2005-01-01

The study evaluates the test-gain benefits of an accelerated desensitization and adaptive attitudes intervention for test-anxious students. College students were screened for high test anxiety. Twenty anxious students, half of them on academic probation, were assigned to an Intervention or to a minimal treatment Control group. The Intervention was…

Comparative Psychotherapy: Rational-Emotive Therapy Versus Systematic Desensitization in the Treatment of Stuttering

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Moleski, Richard; Tosi, Donald J.

1976-01-01

The present study examined the efficacy of rational-emotive psychotherapy and systematic desensitization in the treatment of stuttering. Both therapies, making extensive use of in vivo behavioral assignments, were examined under the presence and absence of in vivo tasks. Results show that rational-emotive therapy was more effective in reducing…

Theophylline is able to partially revert cachexia in tumour-bearing rats

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Olivan Mireia

2012-08-01

Full Text Available Abstract Background and aims The aim of the present investigation was to examine the anti-wasting effects of theophylline (a methylxantine present in tea leaves on a rat model of cancer cachexia. Methods The in vitro effects of the nutraceuticals on proteolysis were examined on muscle cell cultures submitted to hyperthermia. Individual muscle weights, muscle gene expression, body composition and cardiac function were measured in rats bearing the Yoshida AH-130 ascites hepatoma, following theophylline treatment. Results Theophylline treatment inhibited proteolysis in C2C12 cell line and resulted in an anti-proteolytic effect on muscle tissue (soleus and heart, which was associated with a decrease in circulating TNF-alpha levels and with a decreased proteolytic systems gene expression. Treatment with the nutraceutical also resulted in an improvement in body composition and cardiac function. Conclusion Theophylline - alone or in combination with drugs - may be a candidate molecule for the treatment of cancer cachexia.

Neutral endopeptidase up-regulation in isolated human umbilical artery: involvement in desensitization of bradykinin-induced vasoconstrictor effects.

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Pelorosso, Facundo Germán; Halperin, Ana Verónica; Palma, Alejandro Martín; Nowak, Wanda; Errasti, Andrea Emilse; Rothlin, Rodolfo Pedro

2007-02-01

Previous reports show that bradykinin B(2) receptors mediate contractile responses induced by bradykinin (BK) in human umbilical artery (HUA). However, although it has been reported that BK-induced responses can desensitize in several inflammatory models, the effects of prolonged in vitro incubation on BK-induced vasoconstriction in HUA have not been studied. In isolated HUA rings, BK-induced responses after a 5-h in vitro incubation showed a marked desensitization compared with responses at 2 h. Inhibition of either angiotensin-converting enzyme (ACE) or neutral endopeptidase (NEP), both BK-inactivating enzymes, failed to modify responses to BK at 2 h. After 5 h, ACE inhibition produced only a slight potentiation of BK-induced responses. In contrast, BK-induced vasoconstriction at 5 h was markedly potentiated by NEP inhibition. Moreover, NEP activity, measured by hydrolysis of its synthetic substrate (Z-Ala-Ala-Leu-p-nitroanilide), showed a 2.4-fold increase in 5-h incubated versus 2-h incubated tissues, which was completely reversed by cycloheximide (CHX) treatment. Furthermore, CHX significantly potentiated BK-induced responses, suggesting that NEP-mediated kininase activity increase at 5 h depends on de novo protein synthesis. In addition, under NEP inhibition, CHX treatment failed to produce an additional potentiation of BK-induced vasoconstriction. Still, NEP up-regulation was confirmed by Western blot, showing a 2.1-fold increase in immunoreactive NEP in 5-h incubated versus 2-h incubated HUA. In summary, the present study provides strong pharmacological evidence that NEP is up-regulated and plays a key role in desensitization of BK-induced vasoconstriction after prolonged in vitro incubation in HUA. Our results provide new insights into the possible mechanisms involved in BK-induced response desensitization during sustained inflammatory conditions.

Physiological desensitization of carbohydrate permeases and adenylate cyclase to regulation by the phosphoenolpyruvate:sugar phosphotransferase system in Escherichia coli and Salmonella typhimurium. Involvement of adenosine cyclic 3',5'-phosphate and inducer.

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Saier, M H; Keeler, D K; Feucht, B U

1982-03-10

Adenylate cyclase and a number of carbohydrate transport systems are subject to regulation by the phosphoenolpyruvate:sugar phosphotransferase system. These sensitive carbohydrate transport systems are desensitized to regulation by the phosphotransferase system, and adenylate cyclase is deactivated when cells are grown in medium containing cyclic AMP. These effects are specific for cyclic AMP and are potentiated by the genetic loss of cyclic AMP phosphodiesterase. Inclusion in the growth medium of an inducer of a sensitive transport system also promotes desensitization of that particular transport system. Inducer-promoted desensitization is specific for the particular target transport system, while cyclic AMP-promoted desensitization is general and affects several systems. Desensitization of the permeases to regulation, and inactivation of adenylate cyclase, are slow processes which are blocked by chloramphenicol and are therefore presumably dependent on protein synthesis. Several sugar substrates of the phosphotransferase system are capable of regulating the sensitive carbohydrate transport systems. The evidence suggests that desensitization to this regulation does not result from a direct effect on the functioning of Enzyme I, a small heat-stable protein of the phosphotransferase system, HPr, or an Enzyme II of the phosphotransferase system, but specifically uncouples the permease systems from regulation.

Rapid desensitization and resensitization of 5-HT2 receptor mediated phosphatidyl inositol hydrolysis by serotonin agonists in quiescent calf aortic smooth muscle cells

International Nuclear Information System (INIS)

Pauwels, P.J.; Van Gompel, P.; Leysen, J.E.

1990-01-01

Agonist regulation of 5-hydroxytryptamine 2 (5-HT 2 ) receptors was studied in calf aortic smooth muscle cultures incubated in a quiescent, defined synthetic medium that does not stimulate cell proliferation, but that provides cells with supplements that maintain cell viability. In these cells, 5-hydroxytryptamine (5-HT)-induced [ 3 H]inositol phosphates accumulation showed the characteristics of a 5-HT 2 receptor coupled transducing system according to the inhibition of the response by 5-HT 2 antagonists at nanomolar concentrations. The 5-HT 2 receptor coupled response became rapidly desensitized during continued incubation with 5-HT and 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM); nearly full desensitization was obtained in two hours with 10 μM 5-HT and DOM pretreatment. The recovery of the response had a half-live of 5 hours after 2 hours pretreatment and of 9.5 to 12.5 hours after 24 to 96 hours agonist pretreatment. The DOM-induced desensitization of the 5-HT 2 receptor coupled response was fully blocked by 0.1 μM cinanserin. Cinanserin alone did not induce desensitization or up-regulation of the 5-HT 2 receptor coupled response at 0.1 μM

Treatment of Nonphobic Anxiety Disorders: A Comparison of Nondirective, Cognitive, and Coping Desensitization Therapy.

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Borkovec, T. D.; Mathews, Andrew M.

1988-01-01

Compared efficacy of nondirective therapy, coping desensitization, and cognitive therapy in treatment of generalized anxiety disorder and panic disorder. Clients received one treatment and 12 sessions of progressive relaxation training. Results indicated that subjects showed significant and continued improvement on self-report questionnaire, daily…

Self-esteem treatment in anxiety : A randomized controlled crossover trial of Eye Movement Desensitization and Reprocessing (EMDR) versus Competitive Memory Training (COMET) in patients with anxiety disorders

NARCIS (Netherlands)

Staring, A B P; van den Berg, D P G; Cath, D C; Schoorl, M; Engelhard, I M; Korrelboom, C W

BACKGROUND AND PURPOSE: Little is known about treating low self-esteem in anxiety disorders. This study evaluated two treatments targeting different mechanisms: (1) Eye Movement Desensitization and Reprocessing (EMDR), which aims to desensitize negative memory representations that are proposed to

Self-esteem treatment in anxiety : A randomized controlled crossover trial of Eye Movement Desensitization and Reprocessing (EMDR) versus Competitive Memory Training (COMET) in patients with anxiety disorders

NARCIS (Netherlands)

Staring, A. B. P.; van den Berg, D. P. G.; Cath, D. C.; Schoorl, M.; Engelhard, I. M.; Korrelboom, C. W.

2016-01-01

Background and purpose Little is known about treating low self-esteem in anxiety disorders. This study evaluated two treatments targeting different mechanisms: (1) Eye Movement Desensitization and Reprocessing (EMDR), which aims to desensitize negative memory representations that are proposed to

Elimination of Cancer Stem-Like “Side Population” Cells in Hepatoma Cell Lines by Chinese Herbal Mixture “Tien-Hsien Liquid”

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Chih-Jung Yao

2012-01-01

Full Text Available There are increasing pieces of evidence suggesting that the recurrence of cancer may result from a small subpopulation of cancer stem cells, which are resistant to the conventional chemotherapy and radiotherapy. We investigated the effects of Chinese herbal mixture Tien-Hsien Liquid (THL on the cancer stem-like side population (SP cells isolated from human hepatoma cells. After sorting and subsequent culture, the SP cells from Huh7 hepatoma cells appear to have higher clonogenicity and mRNA expressions of stemness genes such as SMO, ABCG2, CD133, β-catenin, and Oct-4 than those of non-SP cells. At dose of 2 mg/mL, THL reduced the proportion of SP cells in HepG2, Hep3B, and Huh7 cells from 1.33% to 0.49%, 1.55% to 0.43%, and 1.69% to 0.27%, respectively. The viability and colony formation of Huh7 SP cells were effectively suppressed by THL dose-dependently, accompanied with the inhibition of stemness genes, e.g., ABCG2, CD133, and SMO. The tumorigenicity of THL-treated Huh7 SP cells in NOD/SCID mice was also diminished. Moreover, combination with THL could synergize the effect of doxorubicin against Huh7 SP cells. Our data indicate that THL may act as a cancer stem cell targeting therapeutics and be regarded as complementary and integrative medicine in the treatment of hepatoma.

Four-Way Kidney Exchange Transplant With Desensitization Increases Access to Living-Donor Kidney Transplant: First Report From India.

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Kute, Vivek B; Patel, Himanshu V; Shah, Pankaj R; Modi, Pranjal R; Shah, Veena R; Kasat, Govind S; Patil, Mayur V; Patel, Jaydeep C; Kumar, Deepak P; Trivedi, Hargovind L

2017-09-26

This study reports our experience of the first 4-way kidney exchange transplant combined with desensitization in India, which allows increased access to living-donor kidney transplant for sensitized patients. Four-way kidney exchange transplant procedures were approved by the ethics committee of our institution and the Organ Transplantation Authorization Committee of state governments of India (as per the Transplantation of Human Organs Act of India). The protocols conformed to Declaration of Istanbul principles and the ethical guidelines of the 1975 Helsinki Declaration. Written informed consent was obtained from patients, donors, and their guardians. In April 2016, our transplant team completed simultaneous 4-way kidney exchange transplant procedures without any medical (rejection and infections) or surgical complications. Reasons for being included for kidney exchange transplant were ABO incom-patible (2 recipients) and sensitization (2 recipients). All 4 recipients had stable graft function with no proteinuria and donor-specific antibody at 11-month follow-up on standard triple immunosup-pression. Patient and graft survival rates were both 100%. To the best of our knowledge, this is the first single-center report of 4-way kidney exchange transplant combined with desensitization from India. This procedure has the potential to expand living-donor kidney transplant in disadvantaged groups (eg, sensitized patients). Recipients who are hard to match due to high panel reactive antibody and difficult to desensitize due to strong donor-specific antibodies can receive a transplant with a combination of kidney exchange and desensitization. Our study suggests that 4-way kidney exchange transplant can be performed in developing countries (India) similar to that shown in programs in developed countries with team work, kidney exchange registry, and counseling.

A Further Assessment of Attention-Placebo Effects and Demand Characteristics in Studies of Systematic Desensitization

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McReynolds, William T.; Tori, Christopher

1972-01-01

It was predicted that phobic Ss receiving systematic desensitization would show greater reductions on both fear-related behavior measures and simulated fear measures than Ss receiving relaxation treatment or no treatment at all. The prediction was confirmed. (Author)

Facilitating and Debilitating Test Anxiety Among College Students and Volunteers for Desensitization Workshops

Science.gov (United States)

Hudesman, John; Wiesner, Ezra

1978-01-01

Examines whether the degree of facilitating and debilitating test anxiety is different for students who volunteer for test anxiety desensitization workshops than it is for the general college population, whether test anxiety in urban community college students is correlated, and whether either or both of the AAT scales are predictive of student…

Comparison of the effect of interferon on two human hepatoma cell lines

Energy Technology Data Exchange (ETDEWEB)

Crespi, M; Schoub, B D; Lyons, S F; Chiu, M N [University of the Witwatersrand, Johannesburg (South Africa). Dept. of Virology

1985-06-01

Two human hepatoma cell lines, the PLC/PRF/5 and the Mahlavu cells, which differ in their production of the hepatitis B surface antigen (HBsAg), responded differently to interferon (IFN). After IFN treatment both cell lines were able to inhibit Sindbis virus replication. Oligo A synthetase (E enzyme) could be activated in the PLC/PRF/5 cells although they were not sensitive to exogenous 2 - 5 oligoadenylic acid (2 - 5 A). In contrast, the Mahlavu cells were sensitive to exogenous 2 - 5 A, but unable to activate the E enzyme. Both cell lines were unable to stimulate phosphorylation of the exogenous initiator factor eIF-2.

Preventive Use of a Resin-based Desensitizer Containing Glutaraldehyde on Tooth Sensitivity Caused by In-office Bleaching: A Randomized, Single-blind Clinical Trial.

Science.gov (United States)

Diniz, Acs; Lima, Snl; Tavarez, RRdJ; Borges, A H; Pinto, Scs; Tonetto, M R; Loguercio, A D; Bandéca, M C

2018-03-23

To evaluate the risk and intensity of bleaching-induced tooth sensitivity (TS) after in-office bleaching following topical application of a resin-based glutaraldehyde desensitizer. Thirty-three patients were randomly assigned to the experimental (Gluma Desensitizer Liquid, Heraeus Kulzer, Hanau, Germany) and placebo groups. The placebo or Gluma Desensitizer Liquid was applied for one minute prior to application of an in-office bleaching gel. Bleaching was performed with 35% hydrogen peroxide gel (three applications × 15 minutes each) over two sessions, one week apart. The color of the anterior teeth was evaluated before and 21 days after treatment using the VITA Classical shade guide, Bleachedguide 3D, and Easyshade spectrophotometer. TS during and after the bleaching was recorded according to the visual analog (VAS) and numerical rating (NRS) scales. All data were submitted to statistical analysis (α=0.05). There was no significant difference in absolute risk or intensity of TS between the two groups (risk and VAS, p=0.93 and 0.31, respectively; NRS, p≥0.45). At the end of the bleaching protocol, tooth whitening was observed in both groups, as evident from color change in shade guide units (ΔSGU, 4.1-7.1; both guides) and overall color change (ΔE, 7.4-9.3 units); however, there were no significant differences in whitening between the two groups ( p>0.11). Gluma Desensitizer Liquid was not able to reduce the risk or intensity of TS. Bleaching efficacy was not affected by application of the desensitizer.

Successful oral desensitization against skin rash induced by alectinib in a patient with anaplastic lymphoma kinase-positive lung adenocarcinoma: A case report.

Science.gov (United States)

Shirasawa, Masayuki; Kubotaa, Masaru; Harada, Shinya; Niwa, Hideyuki; Kusuhara, Seiichiro; Kasajima, Masashi; Hiyoshi, Yasuhiro; Ishihara, Mikiko; Igawa, Satoshi; Masuda, Noriyuki

2016-09-01

Alectinib has been approved for the treatment of patients with anaplastic lymphoma kinase (ALK) gene rearrangement-positive advanced non-small cell lung cancer. In terms of adverse effects, the occurrence of a severe skin rash induced by alectinib is reportedly rare, compared with the occurrence of skin rash induced by epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In the present case report, a 76-year-old woman with ALK-positive lung adenocarcinoma experienced disease progression after undergoing first-line chemotherapy. Subsequently, alectinib was administered as a second-line therapy. However, she discontinued alectinib therapy after 11days because of the occurrence of an alectinib-induced skin rash. Since the skin rash improved within one week, we attempted to perform oral desensitization to alectinib. The patient has not shown any recurrence of the rash or disease progression for 7 months since the successful oral desensitization to alectinib. Here, we describe the first case of successful oral desensitization against a skin rash induced by alectinib in a patient with ALK-positive lung adenocarcinoma. Desensitization to overcome adverse effects and to enable sustained treatment with alectinib should be considered in patients who develop alectinib sensitivities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Desensitization for ABO incompatible kidney transplantation: Experience of a single center in Brazil. ABO incompatible kidney transplantation

Directory of Open Access Journals (Sweden)

Maria Cristina Ribeiro Castro

2017-12-01

Objective: To analyze the patient and the graft survival of the first cohort of Brazilian patients receiving ABO-incompatible transplants. Patients and Methods: From October 2012 to June 2016, we performed 10 ABO incompatible kidney transplantation (KT procedures from a living donor. The desensitization protocol was based on rituximab and PP. All patients received induction with Thymoglobulin and long-term steroids. Tacrolimus and mycophenolate sodium were initiated at the time of desensitization and continued after the transplant. Pre-transplant agglutinin titers varied from 1/32 to 1/512. Five patients also presented anti-HLA specific antibodies, being three T and B positive FCXM at baseline. Results: After a mean follow-up of 30 ( ± 13 months, all patients are alive. One patient lost the graft due to cellular rejection that occurred after reduction of immunosuppressive therapy for an aggressive HPV-related vulvar cancer. The mean serum creatinine concentration is 1.4 ± 0.5 mg/dl. Three episodes of rejection occurred in 3 patients: two cellular and one anti-HLA mediated. Conclusion: Desensitization with Rituximab and PP allowed us to perform transplants from living donors to ABO incompatible recipients in a Brazilian population with good results, even in highly-sensitized patients and in those presenting high anti-ABO agglutinin titers.

Preoperative selective desensitization of live donor liver transplant recipients considering the degree of T lymphocyte cross-match titer, model for end-stage liver disease score, and graft liver volume.

Science.gov (United States)

Hong, Geun; Yi, Nam-Joon; Suh, Suk-won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Lee, Kyungbun; Lee, Kwang-Woong; Park, Myoung Hee; Suh, Kyung-Suk

2014-05-01

Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.

Clinical benefits of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease are not related to urinary eicosanoid release and are accompanied with decreased urine creatinine.

Science.gov (United States)

Makowska, Joanna S; Olszewska-Ziąber, Agnieszka; Bieńkiewicz, Barbara; Lewandowska-Polak, Anna; Kurowski, Marcin; Woźniakowski, Bartłomiej; Rotkiewicz, Arkadiusz; Kowalski, Marek L

2016-05-01

Treatment with acetylsalicylic acid (ASA) after desensitization may be a therapeutic option in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). The mechanisms that lead to improvement in rhinosinusitis and asthma symptoms remain unknown. To attribute the documented clinical effects of ASA treatment of chronic rhinosinusitis and/or asthma to the release of eicosanoid metabolites in urine. Fourteen patients with NERD were successfully desensitized, and, eventually, eight patients were treated with 650 mg of ASA daily for 3 months. In addition to clinical assessments, nuclear magnetic resonance imaging and smell test were performed before and after treatment with ASA. Venous blood and urine were collected before desensitization and after 1 and 3 months of treatment. The levels of urinary leukotrienes (LT) (cysteinyl LT and LTE4) and tetranor PGDM (metabolite of prostaglandin D2) were measured by enzyme-linked immunosorbent assay. Treatment with ASA after desensitization alleviated symptoms of rhinosinusitis, improved nasal patency (mean, 50% decrease in peak nasal inspiratory flow) and sense of smell (fourfold increase in smell test score) in as early as 4 weeks. Clinical improvements were not accompanied by any change in sinonasal mucosa thickness as assessed with nuclear magnetic resonance. Urinary cysteinyl LTs, LTE4, and prostaglandin D2 metabolite remained relatively stable during ASA treatment and did not correlate with clinical improvements. Desensitization was associated with a progressive decrease of urinary creatinine. Clinical improvement in rhinosinusitis and/or asthma after ASA desensitization was not related to concentrations of urinary eicosanoid metabolites. A decrease of urinary creatinine requires further study to determine the renal safety of long-term treatment with ASA after desensitization.

Streptozotocin diabetes attenuates the effects of nondepolarizing neuromuscular relaxants on rat muscles.

Science.gov (United States)

Huang, Lina; Chen, Dan; Li, Shitong

2014-12-01

The hypothesis of this study was that diabetes-induced desensitization of rat soleus (SOL) and extensor digitorum longus (EDL) to non-depolarizing muscle relaxants (NDMRs) depends on the stage of diabetes and on the kind of NDMRs. We tested the different magnitude of resistance to vecuronium, cisatracurium, and rocuronium at different stages of streptozotocin (STZ)-induced diabetes by the EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle preparations from rats after 4 and 16 weeks of STZ treatment. The concentration-twitch tension curves were significantly shifted from those of the control group to the right in the diabetic groups. Concentration giving 50% of maximal inhibition (IC50) was larger in the diabetic groups for all the NDMRs. For rocuronium and cisatracurium in both SOL and EDL, IC50 was significantly larger in diabetic 16 weeks group than those in the diabetic 4 weeks group. For SOL/EDL, the IC50 ratios were significantly largest in the diabetic 16 weeks group, second largest in the diabetic 4 weeks group, and smallest for the control group. Diabetes-induced desensitization to NDMRs depended on the stage of diabetes and on the different kind of muscles observed while was independent on different kind of NDMRs. The resistance to NDMRs was stronger in the later stage of diabetes (16 versus 4 weeks after STZ treatment). Additionally, when monitoring in SOL, diabetes attenuated the actions of neuromuscular blockade more intensely than that in EDL. Nonetheless, the hyposensitivity to NDMRs in diabetes was not relevant for the kind of NDMRs.

Ulcerative colitis patients with an inflammatory response upon mesalazine cannot be desensitized : a randomized study

NARCIS (Netherlands)

Buurman, Dorien J.; De Monchy, Jan G. R.; Schellekens, Reinout C. A.; van der Waaij, Laurens A.; Kleibeuker, Jan H.; Dijkstra, Gerard

Background and aims. Mesalazine is a key drug in the treatment of ulcerative colitis (UC). Intolerance to mesalazine has been described, including fever and gastrointestinal symptoms. Several case reports reported successful desensitization of patients with mesalazine intolerance. The aim was to

Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

Directory of Open Access Journals (Sweden)

Han-En Tsai

Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

Recent advances in live cell imaging of hepatoma cells

Science.gov (United States)

2014-01-01

Live cell imaging enables the study of dynamic processes of living cells in real time by use of suitable reporter proteins and the staining of specific cellular structures and/or organelles. With the availability of advanced optical devices and improved cell culture protocols it has become a rapidly growing research methodology. The success of this technique relies mainly on the selection of suitable reporter proteins, construction of recombinant plasmids possessing cell type specific promoters as well as reliable methods of gene transfer. This review aims to provide an overview of the recent developments in the field of marker proteins (bioluminescence and fluorescent) and methodologies (fluorescent resonance energy transfer, fluorescent recovery after photobleaching and proximity ligation assay) employed as to achieve an improved imaging of biological processes in hepatoma cells. Moreover, different expression systems of marker proteins and the modes of gene transfer are discussed with emphasis on the study of lipid droplet formation in hepatocytes as an example. PMID:25005127

Guideline for radiotherapy of liver cancer

International Nuclear Information System (INIS)

Kishi, Kazushi; Shirai, Shintaro; Satou, Morio; Ueda, Hiroki; Wigg, D.R

2007-01-01

This paper describes bases of radiotherapy (RT) of liver cancer for its application, efficacy, clinical target volume (CTV) and characteristics, dose fractionation and its theory, 2D/3D irradiation, evaluation, and safety. The description here is leading to execute the Guideline 200X to be issued in a near future by the Japanese College of Radiology, and is supplementary to the Guideline in nature. The Guideline is to incorporate the recent progresses of the therapy to complement the previous Guideline 2004. Thus here are described the application of RT to unresectable hepatoma in relation to intervention; characteristics of RT including dose-effect relationships, morphological characteristics of intravascular tumor thrombi (ITT) and CTV, dose fractionation and a/b ratio (liver 2.5 vs hepatoma 7.4), focal lesion in parenchyma, ITT and RT, lymph metastasis, arteriovenous shunt and dissemination, and desensitization in bone and adrenal metastases; prediction of radiation liver damage; and adverse effect by radiation and its control. The evidenced bases of RT are still poor in this field, but the fact that hepatoma, highly sensitive to radiation, exhibits clear dose-response ensures its efficacy if the problems of low tolerance and of breathing movement at irradiation can be solved. (R.T.)

Percutaneous Ethanol Injection of Unresectable Medium-to-Large-Sized Hepatomas Using a Multipronged Needle: Efficacy and Safety

International Nuclear Information System (INIS)

Ho, C.S.; Kachura, J.R.; Gallinger, S.; Grant, D.; Greig, P.; McGilvray, I.; Knox, J.; Sherman, M.; Wong, F.; Wong, D.

2007-01-01

Fine needles with an end hole or multiple side holes have traditionally been used for percutaneous ethanol injection (PEI) of hepatomas. This study retrospectively evaluates the safety and efficacy of PEI of unresectable medium-to-large (3.5-9 cm) hepatomas using a multipronged needle and with conscious sedation. Twelve patients, eight men and four women (age 51-77 years; mean: 69) received PEI for hepatomas, mostly subcapsular or exophytic in location with average tumor size of 5.6 cm (range: 3.5-9.0 cm). Patients were consciously sedated and an 18G retractable multipronged needle (Quadrafuse needle; Rex Medical, Philadelphia, PA) was used for injection under real-time ultrasound guidance. By varying the length of the prongs and rotating the needle, the alcohol was widely distributed within the tumor. The progress of ablation was monitored by contrast-enhanced ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) after each weekly injection and within a month after the final (third) injection and 3 months thereafter. An average total of 63 mL (range: 20-154 ml) of alcohol was injected per patient in an average of 2.3 sessions. Contrast-enhanced CT, ultrasound, or MRI was used to determine the degree of necrosis. Complete necrosis was noted in eight patients (67%), near-complete necrosis (90-99%) in two (16.7%), and partial success (50-89%) in two (16.7%). Follow-up in the first 9 months showed local recurrence in two patients and new lesions in another. There was no mortality. One patient developed renal failure, liver failure, and localized perforation of the stomach. He responded to medical treatment and surgery was not required for the perforation. One patient had severe postprocedural abdominal pain and fever, and another had transient hyperbilirubinemia; both recovered with conservative treatment. PEI with a multipronged needle is a new, safe, and efficacious method in treating medium-to-large-sized hepatocellular carcinoma under conscious

Expectancy, False Galvanic Skin Response Feedback, and Systematic Desensitization in the Modification of Phobic Behavior

Science.gov (United States)

Lick, John

1975-01-01

This study compared systematic desensitization and two pseudotherapy manipulations with and without false galvanic skin response feedback after every session suggesting improvement in the modification of intense snake and spider fear. The results indicated no consistent differences between the three treatment groups. (Author)

Changes in antigen-specific T cell number and function during oral desensitization in cow’s milk allergy enabled with omalizumab

Science.gov (United States)

Bedoret, D; Singh, A K; Shaw, V; Hoyte, E G; Hamilton, R; DeKruyff, R H; Schneider, L C; Nadeau, K C; Umetsu, D T

2012-01-01

Food allergy is a major public health problem for which there is no effective treatment. We examined the immunological changes that occurred in a group of children with significant cow’s milk allergy undergoing a novel and rapid high dose oral desensitization protocol enabled by treatment with omalizumab (anti-IgE mAb). Within a week of treatment, the CD4+ T cell response to milk was nearly eliminated, suggesting anergy in, or deletion of, milk-specific CD4+ T cells. Over the following three months while the subjects remained on high doses of daily oral milk, the CD4+ T cell response returned, characterized by a shift from IL-4 to IFN-γ production. Desensitization was also associated with reduction in milk-specific IgE and a 15-fold increase in milk-specific IgG4. These studies suggest that high dose oral allergen desensitization may be associated with deletion of allergen-specific T cells, without the apparent development of allergen-specific Foxp3+ regulatory T cells. PMID:22318492

Successful Short Desensitization Treatment Protocol with Narrowband UVB Phototherapy (TL-01) in Polymorphic Light Eruption.

Science.gov (United States)

Combalia, A; Fernández-Sartorio, C; Fustà, X; Morgado-Carrasco, D; Podlipnik, S; Aguilera, P

2017-10-01

Polymorphic light eruption (PLE) is a common idiopathic photodermatosis that typically presents with pruritic papular or papulovesicular lesions on sun-exposed skin between spring and autumn. In many subjects PLE is mild, and can usually be prevented by the use of broad-spectrum topical sunscreens and a gradual increase in sunlight exposure. However, in some individuals, sunlight exposure results in florid PLE and they often benefit from prophylactic desensitization treatment using phototherapy in early spring, an artificial method that induces a "hardening" phenomenon. To describe and evaluate the efficacy of a short desensitization protocol, based on a one-month-treatment, administered twice a week with narrow band UVB in subjects with severe polymorphic light eruption (PLE). A retrospective, open planned and non-randomized study to assess the efficacy of UVB phototherapy in prevention of polymorphic light eruption. Fifteen subjects diagnosed with severe PLE were treated with the standard protocol in our Photobiology Unit between 2014 and 2015. The effect of hardening was sustained during follow up in 87.5% of desensitization treatments. A statistically significant association (pPLE and the response to treatment was found. The effect of hardening was maintained in the vast majority of subjects, obtaining a good benefit with no PLE episodes during all the summer. We demonstrate that our standard protocol is effective, and produces a successful outcome for the majority of PLE subjects. Our protocol is shorter than those currently applied, being favourable both for the patient and the physician. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

The roles of selective attention and desensitization in the association between video gameplay and aggression: An ERP investigation.

Science.gov (United States)

Jabr, Mejdy M; Denke, Greg; Rawls, Eric; Lamm, Connie

2018-04-01

A number of studies have indicated that violent video gameplay is associated with higher levels of aggression and that desensitization and selective attention to violent content may contribute to this association. Utilizing an emotionally-charged rapid serial visual presentation (RSVP) task, the current study used two event-related potentials (ERPs) - the N1 and P3 - that have been associated with selective attention and desensitization as neurocognitive mechanisms potentially underlying the connection between gameplay and higher levels of aggression. Results indicated that video game players and non-players differed in N1 and P3 activation when engaged with emotionally-charged imagery. Additionally, P3 amplitudes moderated the association between video gameplay and aggression, indicating that players who display small P3 amplitudes also showed heightened levels of aggression. Follow-up moderational analyses revealed that individuals who play games for many hours and show more negative N1 amplitudes show smaller P3 activation. Together, our results suggest that selective attention to violent content and desensitization both play key roles in the association between video gameplay and aggression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparison of Individualized Covert Modeling, Self-Control Desensitization, and Study Skills Training for Alleviation of Test Anxiety.

Science.gov (United States)

Harris, Gina; Johhson, Suzanne Bennett

1980-01-01

Individualized covert modeling and self-control desensitization substantially reduced self-reported test anxiety. However, the individualized covert modeling group was the only treatment group that showed significant improvement in academic performance. (Author)

Treatment of Speech Anxiety by Cue-Controlled Relaxation and Desensitization with Professional and Paraprofessional Counselors

Science.gov (United States)

Russell, Richard K.; Wise, Fred

1976-01-01

This investigation compared the relative effectiveness of group-administered cue-controlled relaxation and group systematic desensitization in the treatment of speech anxiety. Also examined was the role of professional versus paraprofessional counselors in implementing the treatment program. A description of the cue-controlled relaxation technique…

A study on the thermochemotherapy effect of nanosized As{sub 2}O{sub 3}/MZF thermosensitive magnetoliposomes on experimental hepatoma in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Wang Li; Zhang Jia; Wang Ziyu; Liu Jing; Li Yutao; Zhang Dongsheng [School of Medicine, Southeast University, NO. 87 Ding jia qiao, Nanjing 210009 (China); An Yanli, E-mail: wangli040418@163.com, E-mail: zdszds1222@163.com [Affiliated Zhong-Da Hospital of Southeast University, Nanjing 210009 (China)

2011-08-05

In this paper, we describe the synthesis and characterization of a nanosized, thermosensitive magnetoliposome encapsulating magnetic nanoparticles (MZFs) and antitumor drugs (As{sub 2}O{sub 3}). The nanoliposomes were spherical and mostly single volume, with an average diameter of 128.2 nm. Differential scanning calorimetry (DSC) showed a liposome phase transition temperature of 42.71 deg. C. After that, we studied the liposomes' anti-hepatoma effect in vitro and in vivo. The antitumor effect of the nanoliposomes on human hepatoma cells, SMMC-7721, and changes in expression of apoptosis-related proteins were examined in vitro. The results show that As{sub 2}O{sub 3}/MZF thermosensitive magnetoliposomes combined with hyperthermia had a great impact on the Bax/Bcl-2 ratio, which increased to 1.914 and exhibited a rapid response to induce apoptosis of tumor cells. An in situ rabbit liver tumor model was established and used to evaluate the antitumor effect of combined hyperthermia and chemotherapy following transcatheter arterial embolization with As{sub 2}O{sub 3}/MZF thermosensitive magnetoliposomes. The results demonstrated a strong anti-hepatoma effect, with a tumor volume inhibition rate of up to 85.22%. Thus, As{sub 2}O{sub 3}/MZF thermosensitive magnetoliposomes may play a great role in the treatment of hepatocarcinoma.

Cell damage of hepatoma-22 cells exposed to continuous wave ultrasound.

Science.gov (United States)

Wang, Pan; Wang, Xiaobing; Liu, Quanhong

2012-01-01

The cellular response of hepatoma-22 cells to ultrasonic irradiation and the potential cause for the action were evaluated. Hepatoma-22 cells were subjected to ultrasound irradiation at a frequency of 2.17 MHz and a spatial average intensity of 1.6 W/cm2 for variable periods of time, and several biological parameters were analyzed. The terephthalic acid (TA) dosimetry method was used to evaluate the efficacies of irradiation parameters on the acoustic cavitation activity by monitoring hydroxyl radical (OH) production. Lactate dehydrogenase (LDH) leakage was assayed to investigate cell membrane integrity. The polarization value of fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was measured to monitor plasma membrane fluidity. The malonaldehyde content in cells was determined to reflect lipid peroxidation. Trypan blue exclusion was used to detect cell viability. Additionally, electron microscopy was used to observe morphological changes. The generation of intracellular reactive oxygen species, mitochondria swelling and the loss of mitochondria membrane potential were also investigated. The results showed that 1) the concentration of ·OH production by ultrasonic irradiation in air-saturated cell suspensions increased as ultrasound exposure time increased; 2) compared with control, lactate dehydrogenase leakage, the polarization value of 1,6-diphenyl-1,3,5-hexatriene, malonaldehyde content and cell lysis were significantly elevated when cells were treated by ultrasound for 60 s; 3) cytotoxicity by ultrasound irradiation was also accompanied by an increase in production of intracellular reactive oxygen species and dissipation of mitochondria membrane potential as well as by mitochondria swelling. Presently available information indicates that the plasma membrane and mitochondria are the main targets for ultrasound treatment, and free radicals formation such as ·OH due to ultrasound cavitation may play an important role in mediating these cellular response

Localization of radioiodinated antibody to alpha-fetoprotein in rats with transplanted hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Koji, T; Ishii, N; Kono, K [Nagasaki Univ. (Japan)

1980-11-01

The specific localization of radiolabeled antibody to AFP was investigated in rats bearing subcutaneous transplants of AH-7974 ascites hepatoma. Total body scintigrams 48 to 168 hours after injection of /sup 125/I-anti rat AFP horse antibody showed remarkable localization of radioactivity on the tumors, as a control, a faint outline of tumor was observed by /sup 125/I-normal horse IgG. The tumor/blood radioactivity ratio in the antibody group exceeded 1.0 and was approximately four times higher than that in the control group 7 days after injection, and suggested an active accumulation of radioactive antibody in the tumor tissue. In the subcellular distribution of radioactivity in the tumor tissue, about 30 to 60% of the total radioactivity were found in a fraction of the cell membrane plus nucleus. Furthermore autoradiograms of the fixed tissue sections in the antibody group revealed the specific localization of the radioactivity on the tumor cell surface as black grains.

Evidence for ligand and/or receptor-specific mechanisms of internalization and processing in cultured H35 hepatoma cells

International Nuclear Information System (INIS)

Goldberg, R.I.; Smith, R.M.; Jarett, L.

1987-01-01

Total cell associated (TC) and intracellularly accumulated (IC) 125 I-labeled insulin (INS) or α-2-macroglobulin (α2M) were assessed in cultured H35 hepatoma cells which were preincubated with various agents. Cytochalasin D or sodium azide, which affect microfilament- or energy-dependent receptor internalization, had no significant effects on INS TC or IC but each decreased α2M TC and IC to 50-75% of control. Monensin and chloroquine, acidotrophic agents, each increased INS TC and IC to 150-300% of control yet decreased TC and IC of α2M to 20-50% of control. Only leupeptin, a lysosomal protease inhibitor, caused an increase in both INS and α2M TC and IC. These data suggest significant differences exist in the biochemical regulation or structural routes of INS and α2M receptors and/or receptor-ligand complexes in their (1) internalization, (2) processing in acidic organelles, (3) recycling to the cell surface or in combinations of the above. Biochemical and ultrastructural studies are being performed on the H35 hepatoma cell which will characterize the processing of INS and α2M receptors and provide an explanation for the differences observed

Chronic violent video game exposure and desensitization to violence: Behavioral end event-related brain potential data

NARCIS (Netherlands)

Bartholow, B.D.; Bushman, B.J.; Sestir, M.A.

2006-01-01

Numerous studies have shown that exposure to media violence increases aggression, though the mechanisms of this effect have remained elusive. One theory posits that repeated exposure to media violence desensitizes viewers to real world violence, increasing aggression by blunting aversive reactions

Revisiting Desensitization and Allergen Immunotherapy Concepts for the International Classification of Diseases (ICD)-11.

Science.gov (United States)

Tanno, Luciana Kase; Calderon, Moises A; Papadopoulos, Nikolaos G; Sanchez-Borges, Mario; Rosenwasser, Lanny J; Bousquet, Jean; Pawankar, Ruby; Sisul, Juan Carlos; Cepeda, Alfonso Mario; Li, James; Muraro, Antonella; Fineman, Stanley; Sublett, James L; Katelaris, Constance H; Chang, Yoon-Seok; Moon, Hee-Bom; Casale, Thomas; Demoly, Pascal

2016-01-01

Allergy and hypersensitivity intervention management procedures, such as desensitization and/or tolerance induction and immunotherapy, have not been pondered up to now in the content of International Classification of Diseases (ICD) context because the focus has been on prioritizing the condition implementations. Tremendous efforts have been devoted to implementing allergic and hypersensitivity conditions in the forthcoming ICD-11. However, we consider that it is crucial now to have nomenclature and classification universally accepted for these procedures to be able to provide scientifically consistent proposals into the new ICD-11 platform for the best practice parameters of our specialty. With the aim of promoting a harmonized comprehension and aligning it with the ICD-11 revision, we have reviewed the definitions and concepts currently used for desensitization and/or tolerance induction and immunotherapy. We strongly believe that this review is a key instrument to support the allergy specialty identity into the ICD-11 framework and serves as a platform to perform positive quality improvement in clinical practice. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. All rights reserved.

ABO-Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab.

Science.gov (United States)

Song, G-W; Lee, S-G; Hwang, S; Kim, K-H; Ahn, C-S; Moon, D-B; Ha, T-Y; Jung, D-H; Park, G-C; Kim, W-J; Sin, M-H; Yoon, Y-I; Kang, W-H; Kim, S-H; Tak, E-Y

2016-01-01

ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the largest single-center experience of ABO-incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in-hospital mortality. The cumulative 3-year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO-compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody-mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Phosphatidylcholine synthesis in the rat: The substrate for methylation and regulation by choline

International Nuclear Information System (INIS)

Datko, A.H.; Aksamit, R.R.; Mudd, S.H.

1990-01-01

Two lines of evidence led us to reexamine the possibility that methylation of phosphoethanolamine and its partially methylated derivatives, in addition to methylation of the corresponding phosphatidyl derivatives, plays a role in mammalian phosphatidylcholine biosynthesis: (a) Results obtained by Salerno and Beeler with rat appear to strongly support such a role for methylation of phosphobases; (b) Such reactions have recently been shown to play major roles in phosphatidylcholine synthesis by higher plants. We found that, following continuous labeling of rat liver with L-[methyl-3H]methionine for 10.4 min (intraperitoneal administration) or for 0.75 min (intraportal administration), virtually no 3H was detected in methylated derivatives of phosphoethanolamine, but readily detectable amounts of 3H were present in the base moiety of each methylated derivative of phosphatidylethanolamine. Thus, there was no indication that phospho-base methylation makes a significant contribution. Studies of cultured rat hepatoma cells showed definitively for the first time in a mammalian system that choline deprivation up-regulates the rate of flow of methyl groups originating in methionine into phosphatidylethanolamine and derivatives. Even under these conditions, methylation of phosphoethanolamine bases appeared to play a negligible role

The oncoprotein HBXIP suppresses gluconeogenesis through modulating PCK1 to enhance the growth of hepatoma cells.

Science.gov (United States)

Shi, Hui; Fang, Runping; Li, Yinghui; Li, Leilei; Zhang, Weiying; Wang, Huawei; Chen, Fuquan; Zhang, Shuqin; Zhang, Xiaodong; Ye, Lihong

2016-11-28

Hepatitis B X-interacting protein (HBXIP) as an oncoprotein plays crucial roles in the development of cancer, involving glucose metabolism reprogramming. In this study, we are interested in whether the oncoprotein HBXIP is involved in the modulation of gluconeogenesis in liver cancer. Here, we showed that the expression level of phosphoenolpyruvate carboxykinase (PCK1), a key enzyme of gluconeogenesis, was lower in clinical hepatocellular carcinoma (HCC) tissues than that in normal tissues. Mechanistically, HBXIP inhibited the expression of PCK1 through down-regulating transcription factor FOXO1 in hepatoma cells, and up-regulated miR-135a targeting the 3'UTR of FOXO1 mRNA in the cells. In addition, HBXIP increased the phosphorylation levels of FOXO1 protein by activating PI3K/Akt pathway, leading to the export of FOXO1 from nucleus to cytoplasm. Strikingly, over-expression of PCK1 could abolish the HBXIP-promoted growth of hepatoma cells in vitro and in vivo. Thus, we conclude that the oncoprotein HBXIP is able to depress the gluconeogenesis through suppressing PCK1 to promote hepatocarcinogenesis, involving miR-135a/FOXO1 axis and PI3K/Akt/p-FOXO1 pathway. Our finding provides new insights into the mechanism by which oncoprotein HBXIP modulates glucose metabolism reprogramming in HCC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Oral food desensitization in children with IgE-mediated hen's egg allergy: a new protocol with raw hen's egg.

Science.gov (United States)

Meglio, Paolo; Giampietro, Paolo G; Carello, Rossella; Gabriele, Ida; Avitabile, Simona; Galli, Elena

2013-02-01

Hen's egg allergy affects young children and can cause severe allergic reactions. Avoidance results in dietary limitations and can affect the quality of life, especially in cases where potentially life-threatening reactions exist. Our objective was to desensitize children with moderate-severe IgE-mediated hen's egg allergy over a 6-month period, by introducing increasing and very gradual daily doses of raw hen's egg in order to enable the children to assume 25ml of this food, or to induce tolerance to the highest possible dose. The protocol foresaw the egg reintroduction in the home setting. In this randomized, controlled open study, 20 hen's egg allergic children (10 in the active group) were admitted. A convincing history or a positive double-blind placebo-controlled food challenge confirmed the diagnosis. Oral desensitization was performed with increasing doses starting from 0.27 mg of hen's egg proteins (1 drop of raw hen's egg diluted 1:100). We adopted an original, mathematically calculated protocol in order to ensure a constant, daily increment of doses. 8/10 children (80%) in the active group achieved the daily intake of 25ml over a 6-month period. One child (10%) could tolerate up to 2ml/day while another child (10%) failed the desensitization. Six months after enrolment only 2 children in the control group (20%) could tolerate hen's egg. We successfully desensitized 8/10 children with IgE-mediated hen's egg allergy in a 6-month period. The partial outcome in the child who could tolerate 2ml/day reduced the risk of severe reactions after unnoticed introduction of egg. A regular protocol that ensures a daily constant increase of doses helps to reduce possible adverse events, thus improving safety and effectiveness. © 2012 John Wiley & Sons A/S.

Homologous histamine H1 receptor desensitization results in reduction of H1 receptor agonist efficacy

NARCIS (Netherlands)

Leurs, R; Smit, M J; Bast, A; Timmerman, H

1991-01-01

Prolonged exposure of the guinea-pig intestinal longitudinal smooth muscle to histamine caused homologous desensitization of the H1 receptor, which led to reduced H1 receptor-mediated production of [3H]inositol phosphates as well as to reduced H1 agonist-induced contractions. [3H]Mepyramine binding

In vitro desensitization of beta-adrenoceptors in guinea pig trachea: interactions between beta-adrenoceptor agonists and influence of adenosine and other drugs.

Science.gov (United States)

Matran, R; Naline, E; Advenier, C; Duroux, P

1989-01-01

The aim of this study was to investigate quantitatively the action of and the interaction between beta-adrenergic receptor agonists in desensitizing guinea pig isolated trachea. It was also to evaluate the influence of substances whose effects on desensitization are either disputed (theophylline, indomethacin, ketotifen, hydrocortisone) or unknown (nicardipine, Bay K 8644, fenspiride, adenosine). Tracheal strips were contracted with histamine (5 x 10(-5) M) or acetylcholine (5.10(-5) M) and concentration-response (C/R) curves for various beta-adrenoceptor agonists were determined before and after incubation (20 min to 4 h) with the same beta-adrenoceptor agonist (autodesensitization), with other beta-adrenoceptor agonists (cross-desensitization), or with a beta-adrenoceptor agonist and another substance. Our results show that the autodesensitization induced by isoprenaline is concentration dependent and that concentration dependence is more pronounced with salbutamol and fenoterol than with isoprenaline and adrenaline with respect to autodesensitization: shifts (log unit) of the C/R curves were 0.59 +/- 0.06 (N = 5) for salbutamol (10(-5) M), 0.78 +/- 0.09 (N = 5) for fenoterol (10(-6) M), 0.30 +/- 0.04 (N = 9) for isoprenaline (10(-5) M), and 0.33 +/- 0.05 (N = 5) for adrenaline (10(-5) M). Our studies of cross-desensitization (desensitization to isoprenaline, adrenaline, salbutamol, and fenoterol induced by incubation with isoprenaline 10(-5) M) showed a significantly greater shift in the C/R curves for fenoterol (0.56 +/- 0.08, N = 5) and salbutamol (0.62 +/- 0.05, N = 5) than for adrenaline (0.35 +/- 0.07, N = 5) and isoprenaline itself (0.30 +/- 0.05, N = 9). Of the substances we studied, none modified the desensitization induced by isoprenaline except hydrocortisone and adenosine. Hydrocortisone (10(-8) M) reduced it significantly, although to a negligible extent. Adenosine (3 x 10(-4) M) did not shift the C/R curve to isoprenaline by itself, but incubation

The effect of improvisation-assisted desensitization, and music-assisted progressive muscle relaxation and imagery on reducing pianists' music performance anxiety.

Science.gov (United States)

Kim, Youngshin

2008-01-01

The purpose of this study was to investigate the effects of two music therapy approaches, improvisation-assisted desensitization, and music-assisted progressive muscle relaxation and imagery on ameliorating the symptoms of music performance anxiety (MPA) among student pianists. Thirty female college pianists (N = 30) were randomly assigned to one of two conditions: (a) improvised music-assisted desensitization group (n = 15), or (b) music-assisted progressive muscle relaxation (PMR) and imagery group (n = 15). All participants received 6 weekly music therapy sessions according to their assigned group. Two lab performances were provided; one before and one after the 6 music therapy sessions, as the performance stimuli for MPA. All participants completed pretest and posttest measures that included four types of visual analogue scales (MPA, stress, tension, and comfort), the state portion of Spielberger's State-Trait Anxiety Inventory (STAI), and the Music Performance Anxiety Questionnaire (MPAQ) developed by Lehrer, Goldman, and Strommen (1990). Participants' finger temperatures were also measured. When results of the music-assisted PMR and imagery condition were compared from pretest to posttest, statistically significant differences occurred in 6 out of the 7 measures-MPA, tension, comfort, STAI, MPAQ, and finger temperature, indicating that the music-assisted PMR and imagery treatment was very successful in reducing MPA. For the improvisation-assisted desensitization condition, the statistically significant decreases in tension and STAI, with increases in finger temperature indicated that this approach was effective in managing MPA to some extent. When the difference scores for the two approaches were compared, there was no statistically significant difference between the two approaches for any of the seven measures. Therefore, no one treatment condition appeared more effective than the other. Although statistically significant differences were not found between

Desensitization with plasmapheresis and anti-Cd20 for ABO incompatible kidney transplantation from living donor: experience of a single center in Italy.

Science.gov (United States)

Silvestre, C; Furian, L; Marson, P; Tison, T; Valente, M; Marchini, F; Rossi, B; Bonfante, L; Valerio, F; Cozzi, E; Rigotti, P

2014-09-01

Blood group incompatibility in kidney transplants from a living donor can be successfully overcome by using various desensitization protocols: intravenous immunoglobulin, plasmapheresis (PP), immunoadsorption, and double filtration PP. From July 2010 to October 2013, we performed 10 ABO incompatible kidney transplantation (KT) procedures from a living donor. The desensitization protocol was based on rituximab and PP+cytomegalovirus immune globulin. All patients received induction with basiliximab, except 1 case treated with Thymoglobuline® (ATG) for the simultaneous presence of donor-specific antibody. Tacrolimus and mycophenolate mofetil were initiated at the time of desensitization and continued after the transplant. After a mean follow-up of 11.6±10.4 months, all patients are alive with a functioning graft. The mean serum creatinine concentration at 1 month, 3 months, 6 months, and 1 year was 1.48±0.29, 1.47±0.18, 1.47±0.27, and 1.5±0.27 mg/dl. Three episodes of acute cellular rejection occurred in 2 patients. There was only 1 case of BK virus infection, treated with reduction of immunosuppressive therapy. The protocol biopsy specimens at 1, 3, and 6 months were C4d positive in the absence of acute rejection. Desensitization with rituximab, PP, and anti-cytomegalovirus immune globulin allowed us to perform transplants from living donors to ABO incompatible recipients with excellent results and reduced costs. Copyright © 2014 Elsevier Inc. All rights reserved.

Successful kidney transplantation across a positive complement-dependent cytotoxicity crossmatch by using C1q assay-directed, bortezomib-assisted desensitization

Science.gov (United States)

Lee, Juhan; Park, Borae G.; Jeong, Hyang Sook; Park, Youn Hee; Kim, Sinyoung; Kim, Beom Seok; Kim, Hye Jin; Huh, Kyu Ha; Jeong, Hyeon Joo; Kim, Yu Seun

2017-01-01

Abstract Rationale: Human leukocyte antigen (HLA) is the major immunologic barrier in kidney transplantation (KT). Various desensitization protocols to overcome the HLA barrier have increased the opportunity for transplantation in sensitized patients. In addition, technological advances in solid-phase assays have permitted more comprehensive assessment of donor-specific antibodies. Although various desensitization therapies and immunologic techniques have been developed, the final transplantation decision is still based on the classic complement-dependent cytotoxicity (CDC) crossmatch (XM) technique. Some patients who fail to achieve negative XM have lost their transplant opportunities, even after receiving sufficient desensitization therapies. Patient concerns: A 57-year-old male with end-stage renal disease secondary to chronic glomerulonephritis was scheduled to have a second transplant from his son, but CDC XM was positive. Diagnoses: Initial CDC XM (Initial T-AHG 1:32) and flow-cytometry XM were positive. Anti-HLA-B59 donor specific antibody was detected by Luminex single antigen assay. Interventions: Herein, we report a successful case of KT across a positive CDC XM (T-AHG 1:8 at the time of transplantation) by using C1q assay-directed, bortezomib-assisted desensitization. After confirming a negative conversion in the C1q donor-specific antibody, we decided to perform KT accepting a positive AHG-CDC XM of 1:8 at the time of transplantation. Outcomes: The posttransplant course was uneventful and a protocol biopsy at 3 months showed no evidence of rejection. The patient had excellent graft function at 12 months posttransplant. Lessons: The results of XM test and solid-phase assay should be interpreted in the context of the individual patient. PMID:28953652

Long-term effects of a single exposure to immobilization: a c-fos mRNA study of the response to the homotypic stressor in the rat brain.

Science.gov (United States)

Vallès, Astrid; Martí, Octavi; Armario, Antonio

2006-05-01

A single exposure to a severe emotional stressor such as immobilization in wooden boards (IMO) causes long-term (days to weeks) peripheral and central desensitization of the hypothalamic-pituitary-adrenal (HPA) response to the same (homotypic) stressor. However, the brain areas putatively involved in long-term desensitization are unknown. In the present experiment, adult male rats were subjected to 2 h of IMO and, 1 or 4 weeks later, exposed again to 1 h IMO together with stress-naive rats. C-fos mRNA activation just after IMO and 1 h after the termination of IMO (post-IMO) were evaluated by in situ hybridization. Whereas in most brain areas c-fos mRNA induction caused by the last IMO session was similar in stress-naive (controls) and previously immobilized rats, a few brain areas showed a reduced c-fos mRNA response: ventral lateral septum (LSv), medial amygdala (MeA), parvocellular region of the paraventricular hypothalamic nucleus (pPVN), and locus coeruleus (LC). In contrast, an enhanced expression was observed in the medial division of the bed nucleus stria terminalis (BSTMv). The present work demonstrates that a previous experience with a stressor can induce changes in c-fos mRNA expression in different brain areas in response to the homotypic stressor and suggests that LSv, MeA, and BSTMv may be important for providing signals to lower diencephalic (pPVN) and brainstem (LC) nuclei, which results in a lower physiological response to the homotypic stressor.

Factors Predicting Risk for Antibody-mediated Rejection and Graft Loss in Highly Human Leukocyte Antigen Sensitized Patients Transplanted After Desensitization.

Science.gov (United States)

Vo, Ashley A; Sinha, Aditi; Haas, Mark; Choi, Jua; Mirocha, James; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Jordan, Stanley C

2015-07-01

Desensitization with intravenous immunoglobulin and rituximab (I+R) significantly improves transplant rates in highly sensitized patients, but antibody-mediated rejection (ABMR) remains a concern. Between July 2006 and December 2012, 226 highly sensitized patients received transplants after desensitization. Most received alemtuzumab induction and standard immunosuppression. Two groups were examined: ABMR (n = 181) and ABMR (n = 45, 20%). Risk factors for ABMR, pathology, and outcomes were assessed. Significant risks for ABMR included previous transplants and pregnancies as sensitizing events, donor-specific antibody (DSA) relative intensity scores greater than 17, presence of both class I and II DSAs at transplant and time on waitlist. The ABMR showed a significant benefit for graft survival and glomerular filtration rate at 5 years (P desensitized with I+R who remain ABMR have long-term graft and patient survival. The ABMR patients have significantly reduced graft survival and glomerular filtration rate at 5 years, especially TMA. Severe ABMR episodes benefit from treatment with PLEX + Eculizumab. The DSA-relative intensity scores at transplant was a strong predictor of ABMR. Donor-specific antibody avoidance and reduction strategies before transplantation are critical to avoiding ABMR and improving long-term outcomes.

Tooth sensitivity with a desensitizing-containing at-home bleaching gel-a randomized triple-blind clinical trial.

Science.gov (United States)

Maran, Bianca Medeiros; Vochikovski, Laína; de Andrade Hortkoff, Diego Rafael; Stanislawczuk, Rodrigo; Loguercio, Alessandro D; Reis, Alessandra

2018-05-01

Desensitizing agents are usually included in the composition of bleaching agents to reduce bleaching-induced tooth sensitivity (TS). This randomized clinical trial (RCT) evaluated the risk and intensity of TS and color change after at-home bleaching with a desensitizing-containing (3% potassium nitrate and 0.2% sodium fluoride) and desensitizing-free 10% carbamide peroxide (CP) gel (Whiteness Perfect, FGM). A triple-blind, within-person RCT was conducted on 60 caries-free adult patients. Each participant used the gel in a bleaching tray for 3 h daily for 21 days in both the upper and lower dental arches. The absolute risk and intensity of TS were assessed daily through the 0-10 VAS and NRS scale for 21 days. Color change was recorded using shade guides (Vita Classical and Vita Bleachedguide) and the Easyshade spectrophotometer at baseline, weekly and 30 days after the end of the bleaching. The risk and intensity of TS were evaluated by the McNemar and Wilcoxon Signed Rank tests, respectively. Color change (ΔSGU and ΔE) were evaluated by the Mann-Whitney test and a paired t-test, respectively (α = 0.05). No difference in the TS and color change was observed (p > 0.05). The incorporation of potassium nitrate and sodium fluoride in 10% carbamide peroxide at-home bleaching gel tested in this study did not reduce the TS and did not affect color change (RBR-4M6YR2). Copyright © 2018 Elsevier Ltd. All rights reserved.

Successful desensitization protocol for hypersensitivity reaction probably caused by dabrafenib in a patient with metastatic melanoma.

Science.gov (United States)

Bar-Sela, Gil; Abu-Amna, Mahmoud; Hadad, Salim; Haim, Nissim; Shahar, Eduardo

2015-09-01

Vemurafenib and dabrafenib are both orally bioavailable small molecule agents that block mitogen activated protein kinase signalling in patients with melanoma and BRAF(V600E) mutation. Generalized hypersensitivity reactions to vemurafenib or dabrafenib have not been described. Continuing vemurafenib or dabrafenib therapy despite hypersensitivity reaction is especially important in patients with melanoma and BRAF(V600E) mutation, in whom this mutation plays a critical role in tumour growth. Desensitization protocols to overcome hypersensitivity reactions by gradual reintroduction of small amounts of the offending drug up to full therapeutic doses are available for many anti-cancer agents, including vemurafenib but, to the best of our knowledge, have not been reported for dabrafenib. We describe a patient with metastatic melanoma who developed Type I hypersensitivity reaction to vemurafenib and to subsequent treatment with dabrafenib, and who was successfully treated by drug desensitization which allowed safe prolonged continuation of dabrafenib. The development of hypersensitivity reactions for both dabrafenib and vemurafinib in the current case could be because these drugs have a similar chemical structure and cause a cross-reactivity. However, hypersensitivity reaction to a non-medicinal ingredient shared by the two drugs is also possible. Oral desensitization appears to be an option for patients with hypersensitivity Type I to dabrafenib. This approach may permit clinicians to safely administer dabrafenib to patients who experience hypersensitivity reactions to this life-prolonging medication. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sexual Violence: Psychiatric Healing With Eye Movement Reprocessing and Desensitization

Science.gov (United States)

POSMONTIER, BOBBIE; DOVYDAITIS, TIFFANY; LIPMAN, KENNETH

2011-01-01

Sexual violence, which affects one in three women worldwide, can result in significant psychiatric morbidity and suicide. Eye movement desensitization and reprocessing (EMDR) offers health care providers the option of a brief psychiatric intervention that can result in psychiatric healing in as few as four sessions. Because health care providers often hear stories of sexual violence from their patients, they are in an ideal position to make recommendations for treatment. The purpose of this article is to introduce health care providers to the technique of EMDR, review safety and appropriateness, and discuss clinical and research implications. PMID:20623397

Phosphorus NMR of isolated perfused morris hepatomas

International Nuclear Information System (INIS)

Graham, R.A.; Meyer, R.A.; Brown, T.R.; Sauer, L.A.

1986-01-01

The authors are developing techniques for the study of perfused solid tumors by NMR. Tissue-isolated solid hepatomas were grown to 1-2 cm diameter as described previously. The arterial supply was isolated and the tumors perfused (0.5 - 1.0 ml/min) in vitro at 25 C with a 15% suspension of red blood cells in Krebs-Henseliet solution. 31 P-NMR spectra were acquired at 162 MHz in a specially-designed NMR probe using a solenoidal coil. Intracellular pH (monitored from the chemical shift of inorganic phosphate) and ATP levels were stable for up to 6 hrs during perfusion. During 30 min of global ischemia, ATP decreased by 75% and pH fell from 7.0 to 6.7. These changes were reversed by 1 hr reperfusion. In addition to ATP and phosphate, the spectra included a large resonance due to phosphomonoesters, as well as peaks consistent with glycerylphosphocholine, glyceryl-phosphoethanolamine, phosphocreatine, NAD, and UDPG. However, the most novel feature of the spectra was the presence of an unidentified peak in the phosphonate region (+ 16.9 ppm). The peak was not present in spectra of muscle, liver, brain, kidney, or fat tissues excised from the same animals. They are presently attempting to identify the compound that gives rise to this peak and to establish its metabolic origin

Nature and regulation of the receptors for insulin-like growth factors

International Nuclear Information System (INIS)

Rechler, M.M.; Nissley, S.P.

1985-01-01

Two subtypes of IGF receptors have been identified. Type I IGF receptors have a Mr greater than 300,000 and are composed of disulfide-linked 130,000-dalton (alpha) and approximately 90,000-dalton (beta) subunits. Type I receptors preferentially bind IGF-I but also bind IGF-II and, more weakly, insulin. Type II IGF receptors consist of a 250,000-dalton protein that contains internal disulfide bonds but is not linked to other membrane components. Type II receptors bind IGF-II with higher affinity than IGF-I. They do not interact with even very high concentrations of insulin. Type I IGF receptors and insulin receptors are homologous structures. Type II IGF receptors do not appear to be homologous to type I receptors. Type II receptors do not appear to be downregulated. Insulin acutely upregulates type II IGF receptors in intact rat adipose cells by effecting a redistribution of receptors cycling between a large intracellular pool and the plasma membrane. Insulin and the IGFs elicit the same biological responses, either by cross-reacting with one of the receptors for the heterologous ligand or by concurrent activation of convergent effector pathways by binding to the homologous receptor. Which mechanism is utilized appears to depend more on the tissue than on the biological response. Insulin desensitizes rat hepatoma cells to the actions of insulin and IGFs, mediated by both insulin and IGF receptors, by mechanisms distal to hormone binding and possibly common to IGF and insulin effector pathways

The measurement of cell mediated immunity by radioimmunoassay in desensitizing treatment with acupoints for allergic asthma

International Nuclear Information System (INIS)

Zhou Ronglin; Luan Meiling; Wang Mingsuo; Liu Keliang

1994-05-01

Three mitogens consisted of PHA, PWM, LPS were used to activate lymphocytes. Lymphocyte transformation with radioisotope incorporation of 3 H-TdR was done in 20 patients with allergic asthma and 14 healthy persons as control groups. Cell mediated immune in these cases of desensitizing treatment with acupoints were studied. The experiments showed that the incorporation rates of 3 H-TdR, acupoints were studied. The experiments showed that the incorporation rates of 3 H-TdR, activated by PHA, PWM, LPS, of the allergic asthma patients were P>0.05, P 3 H-TdR in lymphocytes after desensitizing treatment with acupoints compared with that before the treatment tended to be normal. Lymphocyte transformation difference of 3 H-TdR incorporation rates between this group and A or B control groups was significant (P<0.01). This study provides scientific clinical experimental evidences for researching cell mediated immune in attack and curative effects of allergic asthma

pKI values of prazosin and idazoxan for receptors stimulated by neuronally released transmitter in the epididymal portion of rat isolated vas deferens.

OpenAIRE

Mackay, D.; Kengatharan, M.

1994-01-01

1. A new method has been used to measure pKI values of prazosin and idazoxan against neuronally-released transmitter in the epididymal portion of the rat isolated vas deferens. The most reproducible results were obtained with a prolonged antagonist equilibration time (1 h). 2. Under these conditions the pKI of prazosin was practically unaffected by addition of alpha, beta-methylene-adenosine-5'-triphosphate (10 microM) to desensitize purinoceptors. Addition of desmethylimipramine (DMI) (0.3 m...

Tachyphylaxis of juxtaglomerular epithelioid cells to angiotensin II. Differences between the electrical membrane response and renin secretion

DEFF Research Database (Denmark)

Bührle, C P; Hackenthal, E; Nobiling, R

1987-01-01

A study has been made of desensitization of the depolarizing response to angiotensin II of juxtaglomerular epithelioid and vascular smooth muscle cells in the mouse kidney afferent arteriole, of media cells from the mesenteric artery as well as of cultured smooth muscle and mesangial cells. In all...... cell types, desensitization to this effect of angiotensin II was observed. There was no cross-desensitization between angiotensin II and other depolarizing agonists. Hence, it is concluded that this desensitization is specific, i.e. of the tachyphylaxis type. Substances interfering with receptor...... recycling, such as chloroquine and monensin, did not block the recovery of the cells from desensitization after removal of the octapeptide. Desensitization to the action of angiotensin II was also observed with respect to its vasoconstrictor effect in the isolated perfused rat kidney. In contrast...

Heterologous desensitization of adenylate cyclase from pigeon erythrocytes under the action of the catalytic subunit of cAMP-dependent protein kinase

International Nuclear Information System (INIS)

Popov, K.M.; Bulargina, T.V.; Severin, E.S.

1985-01-01

Preincubation of the plasma membranes from pigeon erythrocytes with the catalytic subunit of cAMP-dependent protein kinase leads to desensitization of adenylate cyclase of the erythrocytes. The adenylate cyclase activity, measured in the presence of 10 μM isoproterenol and 50 μM GTP-γ-S, is decreased by 40% in 10 min of incubation, while the activity in the presence of 50 μM GTP-γ-S is decreased by 35% in 20 min. The decrease in the adenylate cyclase activity is due to an increase in the lag phase of activation of the enzyme in the presence of a GTP analog stable to hydrolysis and a decrease in the activity in the steady-state phase of activation. Heterologous desensitization of adenylate cyclase under the action of cAMP-dependent protein kinase is coupled with a decrease in the number of β-adrenoreceptors capable of passing into a state of high affinity for antagonists in the absence of guanylic nucleotides. The influence of the catalytic subunit on adenylate cyclase entirely models the process of desensitization of the enzyme absorbed in the influence of isoproterenol or cAMP on erythrocytes

Systematic Desensitization and Assertive Training in the Treatment of Speech Anxiety in Middle-School Students

Science.gov (United States)

Johnson, Tom; And Others