Sample records for plasma thyroxine t4

  1. Establishment of an Enzyme Linked Immunosorbent Assay for Total ThyroxineT4

    Institute of Scientific and Technical Information of China (English)


    A sensitive and specific ELISA for total thyroxineT4) is established. The anti-T4 antibody is coatedon the microtiter plate, the T4 antigen is conjugated to the biotin. The label is horseradish peroxidase(HRP)

  2. Concentrações plasmáticas de testosterona, triiodotironina (T3 e tiroxina (T4 em bodes submetidos ao estresse calórico Plasma concentrations of testosterone, triiodothyronine (T3, and thyroxine (T4 in bucks submitted to heat stress

    Directory of Open Access Journals (Sweden)

    L.A. Coelho


    Full Text Available Para verificar o efeito do estresse calórico (EC nas concentrações plasmáticas de testosterona, triiodotironina (T3 e tiroxina (T4, oito bodes, das raças Saanen (n=4 e Alpina (n=4, foram mantidos em câmara bioclimática, sob condições de termoneutralidade (13,0ºC a 26,7ºC durante 30 dias e, após um período (60 dias de descanso, submetidos ao EC (23,7ºC a 34,0ºC por 30 dias. Para minimizar as variações sazonais nos perfis hormonais devido ao fotoperíodo, durante toda fase experimental, incluindo a de adaptação em condições de termoneutralidade (30 dias, o fotoperíodo foi controlado utilizando-se alternância de dias longos (16h de luz e 8h de escuro e de dias curtos (8h de luz e 16h de escuro a cada 30 dias. As amostras de sangue foram coletadas duas vezes por semana durante cinco semanas. No conjunto das raças, o EC não influenciou (P>0,05 as concentrações de testosterona (1,8±0,2 vs 1,3±0,2ng/ml e nem a de T4 (52,7±2,8 vs 50,0±2,8ng/ml. Houve declínio (PTo verify the effect of heat stress (HS on plasma testosterone, triiodothyronine (T3, and thyroxine (T4 concentrations, eight Saanen (n=4 and Alpine Brown (n=4 bucks were kept in climate chamber under thermal neutral conditions (13.0ºC to 26.7ºC for 30 days. After a resting period (60 days, the same bucks were submitted to heat stress (23.7ºC to 34.0ºC for another 30 days. To neutralize the seasonal variations of hormonal profiles throughout the period, the photoperiod was controlled every 30 days altering long (16 hours of light and 8 hours of darkness and short days (8 hours of light and 16 hours of darkness. The blood samples were collected twice a week during five weeks. In both breeds, there was no effect of HS (P>0.05 on plasma concentrations of testosterone (1.8±0.2 vs 1.3±0.2ng/ml and T4 (52.7±2.8 vs 50.0±2.8ng/ml. There was a decline (P<0.01 of plasma T3 concentrations (1.3±0.1 vs 1.0±0.1ng/ml after HS treatment, but this reduction was only


    Nuclear receptor agonists phenobarbital (PB), 3-methylcholanthrene (3MC), pregnenolone-16a-carbonitrile (PCN), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and 2,2' ,4,4'-tetrabromodiphenyl ether (BDE 47) decrease serum thyroxine (T4) in rats. This decrease is thought to occur th...


    Previous studies demonstrate that in vivo exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) decrease serum thyroxine (T4) levels in rats. This decrease is thought to occur through the induction of hepatic metabolizing enzymes ...

  5. Effects of hepatic enzyme inducers on thyroxine (T4) catabolism in primary rat hepatocytes (United States)

    Nuclear receptor agonists such as phenobarbital (PB), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and 3-methylcholantrene (3-MC) decrease circulating thyroxine (T4) concentrations in rats. It is suspected that this decrease occurs through the induction of hepatic metabolizing en...


    Nuclear receptor agonists such as 3-methylcholantrene (3-MC), phenobarbital (PB), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and, pregnenolone-16a-carbonitrile (PCN) decrease serum thyroxine (T4) concentrations in rats. It appears that this decrease occurs through the induction...

  7. Effect of thyroxine on cellular oxygen-consumption and glucose uptake: evidence of an effect of total T4 and not "free T4"

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L E


    in human mononuclear blood cells. Cells were incubated in protein free medium and in human serum totally depleted of thyroid hormones by resin treatment and fixed amounts of T4 (total T4 = 0-50-100-5000 nmol/l; free T4 = 0-5-11-5600 pmol/l) were added. Thyroxine stimulated glucose uptake and oxygen...

  8. Thyroxine softgel capsule in patients with gastric-related T4 malabsorption. (United States)

    Santaguida, Maria Giulia; Virili, Camilla; Del Duca, Susanna Carlotta; Cellini, Miriam; Gatto, Ilenia; Brusca, Nunzia; De Vito, Corrado; Gargano, Lucilla; Centanni, Marco


    The key role of an intact gastric acid secretion for subsequent intestinal T4 absorption is supported by an increased requirement of thyroxine in patients with gastric disorders. A better pH-related dissolution profile has been described in vitro for softgel T4 preparation than for T4 tablets. Our study was aimed at comparing softgel and tablet T4 requirements in patients with gastric disorders. A total of 37 patients with gastric-related T4 malabsorption were enrolled, but only 31 (28F/3M; median age = 50 years; median T4 dose = 2.04 μg/kg/day) completed the study. All patients were in long-lasting treatment (>2 years) with the same dose of T4 tablets when treatment was switched to a lower dose of softgel T4 capsules (-17 %; p = 0.0002). Assessment of serum FT4 and TSH was carried out at baseline and after 3, 6, 12, and 18 months after the treatment switch. In more than 2/3 of patients (good-responders n = 21), despite the reduced dose of T4, median TSH values were similar at each time point (p = 0.3934) with no change in FT4 levels. In the remaining patients (poor-responders n = 10), TSH levels were significantly higher at each time point than at baseline (p < 0.0001). To note, in five of them intestinal comorbidity was subsequently detected. Comorbidity associated with poor-responders status was the only significant predictor in multivariate analysis (OR = 11.333). Doses of softgel T4 capsules lower than T4 tablet preparation are required to maintain the therapeutic goal in 2/3 of patients with impaired gastric acid secretion.

  9. Effect of adjuvant lithium on thyroxine (T4) concentration after radioactive iodine therapy

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    Hammond, Emmanuel NiiBoye; Vangu, Mboyo-Di-Tamba Heben Willy [University of the Witwatersrand, Division of Nuclear Medicine and Molecular Imaging, Department of Radiation Sciences, Johannesburg (South Africa)


    To study the effect of adjuvant lithium on serum thyroxine (T4) concentrations in patients treated with radioactive iodine (RAI) therapy in our environment. This was a prospective simple randomized comparative, experimental cohort study of patients with hyperthyroidism referred for RAI ablation therapy in the two main academic hospitals in Johannesburg between February 2014 and September 2015. Amongst the 163 participants in the final analysis, 75 received RAI alone and 88 received RAI with lithium. The difference in mean T4 concentrations at 3 months between the RAI-only group (17.67 pmol/l) and the RAI with lithium group (11.55 pmol/l) was significant with a small effect size (U = 2328.5, Z = -2.700, p = 0.007, r = 0.01). Significant decreases in T4 concentrations were observed as early as 1 month after RAI (p = 0.0001) in the RAI with lithium group, but in the RAI-only group, significant decreases in T4 concentrations were observed only at 3 months after RAI therapy (p = 0.000). Women and patients with Graves' disease who received RAI with adjuvant lithium also showed significant decreases in T4 concentrations at 1 month (p = 0.002 and p = 0.003, respectively). Adjuvant lithium leads to an earlier and better response to RAI therapy with lower T4 concentrations that are achieved earlier. This earlier response and decrease in T4 concentrations were noted in patients with Graves' disease and nodular goitre, and in women with hyperthyroidism who received adjuvant lithium therapy. (orig.)

  10. Measurement of thyroid hormones (thyroxine, T4; triiodothyronine, T3) in captive nondomestic felids. (United States)

    Rodini, Débora Cattaruzzi; Felippe, Erika Cristiane Gutierrez; Oliveira, Cláudio Alvarenga


    The aim of this research was to obtain basic values for the evaluation of thyroid function in nondomestic felids. Serum thyroid hormone concentrations (thyroxine, T4; triiodothyronine, T3) were measured by radioimmunoassay in 145 cats, representing nine species of captive nondomestic felids: jaguar (Panthera onca), n = 49; puma (Puma concolor), n = 10; ocelot (Leopardus pardalis), n = 22; oncilla (Leopardus tigrinus), n = 12; geoffroy (Oncifelis geoffroyi), n = 4; jaguarundi (Herpailurus yaguarondi), n = 8; margay (Leopardus wiedii), n = 7; lion (Panthera leo), n = 26; and tiger (Panthera tigris), n = 7. For each species, mean +/- SEM of T3 and T4, respectively, were as follows: jaguar, 0.56 +/- 0.03 and 9.7 +/- 0.8 ng/ml; puma, 0.67 +/- 0.04 and 11.2 +/- 1.2 ng/ml; ocelot, 0.48 +/- 0.03 and 13.8 +/- 1.5 ng/ml; oncilla, 0.43 +/- 0.03 and 10.0 +/- 1.6 ng/ml; geoffroy, 0.44 +/- 0.04 and 8.0 +/- 0.16 ng/ml; jaguarundi, 0.7 +/- 0.03 and 5.0 +/- 1.0 ng/ml; margay, 0.48 +/- 0.04 and 12.2 +/- 2.3 ng/ml; lion, 0.43 +/- 0.02 and 5.7 +/- 2.6 ng/ml; and tiger, 0.66 +/- 0.03 and 12.6 +/- 0.9 ng/ml. Within species, T3 and T4 concentrations did not differ (P > 0.05) between males and females.


    Nuclear receptor agonists such as phenobarbital (PB), 3-methylcholantrene (3MC), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and, pregnenolone-16a-carbonitrile (PCN) decrease serum thyroxine (T4) concentrations in rats. This decrease is thought to occur through the induction of ...

  12. Comparison of preventive effect of T3 and T4 on thyroxine release from thyroid induced by endogeneous TSH after TRH injection. (United States)

    Kokesová, H; Langer, P; Gschwendtová, K; Sadlon, J; Bukovská, M


    Comparison of Preventive Effect of T3 and T4 on Thyroxine Release from Thyroid Induced by Endogenous TSH after TRH Injection. Endocrinologia Experimentalis 11, 91-98, 1977. The technique of frequent blood sampling through polyethylene tubings inserted into blood vessels while maintaining isovolemia was used in pentobarbiturate anaesthetized rats weighing 250--300 g. The animals were fed low iodine diet for 4 weeks and injected 125I- (5 microgram Ci per animal daily) for 6 days begining from 8th day before the experiment. The effect of 25 microgram TRH injected through a cannula inserted into carotid artery in cranial direction was evaluated as per cent increase of labelled thyroxine in plasma at 120 min after the injection compared to its level at 30 min. Moreover, the inhibitory effect of various doses of thyroxine (T4; 5, 20 and 80 nmol kg-1) and triiodothyronine (T3; 1.25 and 5 nmol kg-1) injected i.v. at the intervals of 10, 20, 30, 60 and 180 min prior to TRH was investigated. It was found that the effect was time dependent, being negligible after 10 or 20 min, while after 60 and 180 min the increase of labelled T4 after TRH was fully prevented by 20 and 80 nmol T4 kg-1 and by 5 nmol T3 kg-1. The other doses (i. e. 5 nmol T4 kg-1 and 1.25 nmol T3 kg-1) were without effect. Thus, T3 was found to be significantly more active than equimolar doses of T4.

  13. [Thyroxine (T4) and tri-iodothyronine (T3) determinations: techniques and value in the assessment of thyroid function]. (United States)

    Sapin, R; Schlienger, J-L


    Hormonal production of the thyroid gland is constituted of thyroxine or T4 (80%) and triiodothyronine or T3 (20%). In the circulation, whole T4 originates from thyroid secretion but most of T3 (80%) is produced extrathyroidally from T4 deiodination. Conversion of T4 to T3 may be influenced by various conditions and circulating T3 is a less reliable reflection of thyroid hormone production than T4. In serum most of T4 and T3 is bound to binding proteins and only 0.02% of T4 and 0.3% of T3 is free. Because of their higher diagnostic performance, free T4 (FT4) and free T3 (FT3) measurements have superseded total (free + bound) hormone determination. Total hormone measurements remain useful for research studies or in case of severe hyperthyroidism. Equilibrium dialysis/RIA is considered as the reference method for free hormone measurements. Routine clinical laboratories use automated direct two-step or one-step immunoassays with a high molecular weight ligand or labelled antibody. Free hormone measurement remains technically demanding, especially in sera from severe non-thyroid ill patients with low serum thyroxine binding capacity. Interference from anti-thyroid hormone antibodies and familial dysalbuminemic hyperthyroxinemia depends on the assay method, but is now less marked and less frequently detected. To be able to correctly interpret the results of an assay, it is necessary to assess its performance in biologically and clinically well-characterised serum samples. FT4, and FT3 measurements, if FT4 is normal and hyperthyroidism suspected, are used to confirm and assess the level of hypo and hyperthyroidism (overt or subclinical). When the thyroidal status is unstable (first months of a thyroid treatment, altered L-T4 dose, subacute thyroiditis) or when the hypothalamic-pituitary function is disturbed (central hypothyroidism), TSH determination is diagnostically misleading and only free hormone measurements are reliable for thyroid function assessment.

  14. Self-Assembly of Pyridine-Modified Lipoic Acid Derivatives on Gold and Their Interaction with Thyroxine (T4

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    Pierangelo Metrangolo


    Full Text Available Pyridyl derivatives of lipoic acid were prepared as ligands for the study of the interaction with thyroxine (T4. Thin self-assembled films of the ligands were prepared in 70% ethanol on gold and their interaction with T4 was studied by titration experiments in an aqueous buffer solution using Surface Plasmon Resonance (SPR. The thickness and refractive index of the ligand layers were calculated from SPR spectra recorded in two media, also allowing for surface coverage and the density of the layers to be estimated. Two ligands, a 4-pyridyl and a bis(2-hydroxyethyl derivative of lipoic acid, were selected to investigate the feasibility for producing molecularly imprinted self-assembled layers on gold for T4. The methodology was to co-assemble T4 and the ligand onto the gold surface, elute the T4 from the layer under alkaline conditions, and study the rebinding of T4 to the layer. Multiple elution/rebinding cycles were conducted in different buffer solutions, and rebinding of T4 could be observed, with a moderate binding affinity that depended greatly on the solvent used. More optimal binding was observed in HBS buffer, and the affinity of the interaction could be slightly increased when the 4-pyridyl and bis(2-hydroxy-ethyl derivatives of lipoic acid were combined in the imprinted layer.

  15. Self-Assembly of Pyridine-Modified Lipoic Acid Derivatives on Gold and Their Interaction with Thyroxine (T4) (United States)

    Albers, Willem M.; Milani, Roberto; Tappura, Kirsi; Munter, Tony; Resnati, Giuseppe; Metrangolo, Pierangelo


    Pyridyl derivatives of lipoic acid were prepared as ligands for the study of the interaction with thyroxine (T4). Thin self-assembled films of the ligands were prepared in 70% ethanol on gold and their interaction with T4 was studied by titration experiments in an aqueous buffer solution using Surface Plasmon Resonance (SPR). The thickness and refractive index of the ligand layers were calculated from SPR spectra recorded in two media, also allowing for surface coverage and the density of the layers to be estimated. Two ligands, a 4-pyridyl and a bis(2-hydroxyethyl) derivative of lipoic acid, were selected to investigate the feasibility for producing molecularly imprinted self-assembled layers on gold for T4. The methodology was to co-assemble T4 and the ligand onto the gold surface, elute the T4 from the layer under alkaline conditions, and study the rebinding of T4 to the layer. Multiple elution/rebinding cycles were conducted in different buffer solutions, and rebinding of T4 could be observed, with a moderate binding affinity that depended greatly on the solvent used. More optimal binding was observed in HBS buffer, and the affinity of the interaction could be slightly increased when the 4-pyridyl and bis(2-hydroxy-ethyl) derivatives of lipoic acid were combined in the imprinted layer. PMID:23389045

  16. Massive thyroxine intoxication: evaluation of plasma extraction. (United States)

    Binimelis, J; Bassas, L; Marruecos, L; Rodriguez, J; Domingo, M L; Madoz, P; Armengol, S; Mangues, M A; de Leiva, A


    Six patients were admitted after erroneous massive intake of levothyroxine (70-1200 mg over an interval of 2-12 days). All patients developed classical symptoms of thyrotoxicosis within 3 days of the first dose; five patients presented grade II-III coma and one became stuporous (days 7-10). Two patients developed left ventricular failure and three had arrhythmias (days 8-11). Total thyroid hormone levels in serum on admission ranged 935-7728 nmol/l for T4 (TT4) and 23-399 nmol/l for T3 (TT3). All patients received treatment with hydrocortisone and Propranolol. Propylthiouracil was also given in 3 cases. Extractive techniques (charcoal haemoperfusion and/or plasmapheresis) were initiated 8-14 days after the first dose of L-T4. The plasma disappearance rate (K) of TT4 with plasmapheresis was 30 times higher, on average, than under standard medical treatment (M). Also, K of TT4 under haemoperfusion was about five times higher than K under M. K changes for TT3 were higher under haemoperfusion than under plasmapheresis. Furthermore, extractive procedures shortened the average half life of TT4, (from 106.5 +/- 44.6 to 59.7 +/- 20.2 h, p less than 0.05).

  17. Thyroxine (T 4-RIA) and triiodothyronine (T 3-RIA) serum levels in sheep fed on Leucaena Leucocephala; Niveis sericos de tiroxina (T4-RIA) e triiodotinonina (T3-RIA) em ovinos alimentados cm Leucaena Leucocephala LAM

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    Pessoa, J.M.; Rodriguez, N.M. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Escola de Veterinaria; Cardoso, W.M. [Maranhao Univ., Sao Luis, MA (Brazil). Escola de Medicina Veterinaria; Velez, C.E.S.


    The aim of this work is to study the toxicity of Leucaena leucocephala on thyroxine and triiodothyronine serum concentration. Results indicate that ovine T 4 and T 3 serum levels do not decrease with Leucaena leucocephala feeding, sohen proreided for 41 days. (author). 10 refs, 1 tab.

  18. Effect of combination therapy with thyroxine (T4) and 3,5,3'-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study

    DEFF Research Database (Denmark)

    Nygaard, Birte; Jensen, Ebbe Winther; Kvetny, Jan


    the effect of combination therapy with thyroxine (T(4)) and T(3) versus T(4) monotherapy in patients with hypothyroidism on stable T(4) substitution. Study design Double-blind, randomised cross-over. Fifty micrograms of the usual T(4) dose was replaced with either 20 microg T(3) or 50 microg T(4) for 12...... weeks, followed by cross-over for another 12 weeks. The T(4) dose was regulated if needed, intending unaltered serum TSH levels. Evaluation Tests for quality of life (QOL) and depression (SF-36, Beck Depression Inventory, and SCL-90-R) at baseline and after both treatment periods. Inclusion criteria......, indicating a positive effect related to the combination therapy. Forty-nine percent preferred the combination and 15% monotherapy (P=0.002). Serum TSH remained unaltered between the groups as intended. CONCLUSION: In a study design, where morning TSH levels were unaltered between groups combination therapy...

  19. The effect of severe starvation and captivity stress on plasma thyroxine and triiodothyronine concentrations in an antarctic bird (emperor penguin). (United States)

    Groscolas, R; Leloup, J


    The effect of confinement and severe starvation on the plasma thyroxine (T4) and triiodothyronine (T3) concentrations was determined in emperor penguins (Aptenodytes forsteri). During their annual cycle, emperor penguins fast freely for periods of up to 4 months and may thus represent a unique subject to study endocrine adaptations to fasting. Plasma T4 concentrations progressively decreased following capture and confinement of naturally fasting penguins, and within 15-20 days stabilized at levels three times lower than in free-living penguins. A transient fourfold increase in plasma T3 concentration developed within the day following confinement in parallel with a rise in daily body mass loss. Both plasma T3 concentration and mass loss subsided to normal levels within 15 days. The decrease in plasma T4 concentration is in accordance with the well-known inhibitory effect of stress on thyroid function in birds and mammals, whereas the transient increase in plasma T3 concentration seems related to enhancement of energy expenditure as a consequence of restlessness. Starvation severe enough to exhaust fat stores and to activate protein catabolism induced a 6- and 5 to 10-fold fall in plasma T4 and T3, respectively. This is in marked contrast with maintenance of plasma thyroid levels during long-term natural fasting associated with protein sparing (R. Groscolas and J. Leloup (1986) Gen. Comp. Endocrinol. 63, 264-274). Surprisingly, there was a final reincrease in plasma T4 concentration in very lean penguins. These results suggest that the effect of starvation on plasma thyroid hormones seems to depend on how much protein catabolism is activated and demonstrate the acute sensitivity of thyroid hormone balance to stress in penguins.

  20. Free T4 (Thyroxine) Test (United States)

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  1. Matrix Interference in Serum Total ThyroxinT4) Time-resolved Fluorescence Immunoassay (TRFIA) and Its Elimination With the Use of Streptavidin-biotin Separation Technique

    Institute of Scientific and Technical Information of China (English)


    In development of serum total thyroxin TRFIA using the surface second-antibody (S-Ab) as separation agent, a significant bias of measurement caused by matrix interference when the surface S-Ab shows a relatively low binding capacity for primary anti-T4 monoclonal antibody (McAb) is studied. The bias ranges from 10% to 78%, depending on the matrix of individual samples and the binding capacity of the surface S-Ab prepared. So, a new separation system based on the use of a highly active surface streptavidin and biotinylated anti-T4 McAb is employed. The results indicate

  2. Evaluation of seasonal and daily changes of plasma thyroxine and cortisol levels in wild masu salmon Oncorhynchus masou, sampled by a Japanese fishing method. (United States)

    Munakata, A; Miura, G; Matsuda, H


    A new fish sampling method was developed using a Japanese bait fishing rod (8-9 m carbon rod and a nylon line with a small fine wire single hook), which is considered to catch wild salmonid juveniles with low sampling stress. Using this method, seasonal and daily changes of plasma thyroxine (T4 ) and cortisol levels were examined in wild parr, pre-smolts and smolts of masu salmon Oncorhynchus masou in contiguous locations in a coastal river (Kesen River; 44 km) in northern Honshu Island, Japan, overlapping the period of smoltification and seaward migration from August to March. Plasma T4 and cortisol were low in 0+ and 1+ year parr caught in August and September. In March, some yearling (1+ year) fish, which were judged as pre-smolts, and smolts appeared mainly in mid and lower reaches, while parr (0+ and 1+ year parr) continued to appear in the upper and mid reaches. In March, 1+ year pre-smolts and smolts showed high plasma T4 levels while the levels of 1+ year parr were low. During March 2008-2010, plasma T4 levels of 1+ year pre-smolts and smolts had high levels from early to mid-March, whereas plasma cortisol levels of 1+ year smolts were low in early March and increased towards mid-March. Based on these data, plasma cortisol increases probably occur following the increases of plasma T4 levels to lead the 1+ year O. masou to the completion of smoltification and initiation of seaward migration. © 2014 The Fisheries Society of the British Isles.


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    Sanely Lourenço da Costa


    Full Text Available The aim of this study was to investigate the interaction of human FSH (10ng/ml with T4 (20ng/mL on survival, activation and growth of preantral follicles cultured in vitro for 28 days. Fragments of non-cultured and cultured ovarian tissue were processed for classic histology and transmission electron microscopy. The results showed a reduction in the survival rate in all the media tested (one to 28 days when compared to the fresh control. However the treatment with T4/hFSH for seven days of culture maintained the rate similar to the control. The media tested by one and 28 days reduced the percentage of primordial follicles in all periods of culture. However, T4/hFSH on day one of culture remained similar to the fresh control. None of the media were able to keep the percentage of the developing follicles. It was observed that the follicular diameter in the medium with T4/hFSH remained similar to the fresh control. The ultrastructural analysis confirmed the integrity of follicles cultured for seven days in a medium supplemented with T4/hFSH. In conclusion, the medium with T4/hFSH is able to maintain the survival, promote the activation, and the ultrastructural integrity of caprine preantral follicles for until seven days.

  4. Increased urinary excretion of triiodothyronine (T3) and thyroxine (T4) and decreased serum thyreotropic hormone (TSH) induced by motion sickness. (United States)

    Habermann, J; Eversmann, T; Erhardt, F; Gottsmann, M; Ulbrecht, G; Scriba, P C


    We exposed 35 male subjects to a rotary chair and motion sickness was provoked by Coriolis effect. This stress caused an increased excretion of urinary T3 and T4 and a decrease of TSH levels in serum. The increment in urinary excretion of thyroid hormones may serve as a very useful measure for the quantitation of physical stress. Although no statistically significant change of T3, T4, and TBG levels in serum could be observed by the employed techniques, the hypothesis is favoured that motion sickness probably causes an immeasurably small increase of the free thyroid hormone fraction in serum, thereby increasing urinary excretion of T3 and T4 and, in turn, decreasing TSH secretion. Physical or psychological stress situations involve most of the endocrine systems. Contadictory results have been reported in the literature concerning the relationship between thyroid function and stress.

  5. Luteinizing hormone-releasing hormone induces thyroxine release together with testosterone in the neotenic axolotl Ambystoma mexicanum. (United States)

    Jacobs, G F; Kühn, E R


    In male neotenic axolotls Ambystoma mexicanum plasma concentrations of thyroxine (T4) and testosterone were increased following intravenous injection of 10 micrograms luteinizing hormone-releasing hormone. A dose of 50 micrograms influenced only plasma T4 levels. This observation suggests for the first time that a hypothalamic hormone is capable of stimulating the thyroidal axis in the neotenic axolotl.

  6. Thyroxine and triiodothyronine in plasma and thyroids of the neotenic and metamorphosed axolotl Ambystoma mexicanum: influence of TRH injections. (United States)

    Jacobs, G F; Michielsen, R P; Kühn, E R


    Circulating levels of T3 and T4, as well as T3 and T4 content of the thyroid glands were measured by radioimmunoassay in the neotenic and metamorphosed axolotl Ambystoma mexicanum. In the two experiments which were performed plasma T4 concentrations were more elevated in metamorphosed axolotls, especially in the first experiment (2.12 +/- 0.40 ng/ml vs. 369 +/- 30 pg/ml). T3 plasma values which were only estimated in the second experiment were about five times higher in metamorphosed animals (63.2 +/- 7.4 pg/ml vs. 12.5 +/- 0.8 pg/ml). Also the thyroid hormone content of the glands was higher after metamorphosis. Nevertheless the neotenic gland still contained considerable amounts of T3 (14.7 +/- 1.8 ng and 48.3 +/- 4.8 ng/thyroid, respectively, in the first and second experiment) and T4 (530 +/- 61 ng; 2173 +/- 291 ng/thyroid). Because of the higher T3/T4 ratio found in the plasma compared to the thyroid gland, it was suggested that circulating T3 may be derived partly from peripheral T4 conversion, mainly after metamorphosis. An intravenous injection of 10 micrograms synthetic TRH was able to induce a very significant increase of the plasma T4 concentration (which was maintained during 24 hr) in the metamorphosed axolotls of the first experiment, however, not in those of the second experiment nor in the neotenic animals. Following an injection of 10 mU bovine TSH (first experiment) circulating levels of T4 were raised in both groups. The opposing TRH results could be related with the different control levels of T4 in the two experiments. However, the results indicate that TRH is capable of functioning as a possible thyrotropin-releasing factor in the metamorphosed axolotl.

  7. Thermionic plasma injection for the Lockheed Martin T4 Compact Fusion Reactor experiment (United States)

    Heinrich, Jonathon


    Lockheed Martin's Compact Fusion Reactor (CFR) concept relies on diamagnetic confinement in a magnetically encapsulated linear ring cusp geometry. Plasma injection into cusp field configurations requires careful deliberation. Previous work has shown that axial injection via a plasma gun is capable of achieving high-beta conditions in cusp configurations. We present a pulsed, high power thermionic plasma source and the associated magnetic field topology for plasma injection into the caulked-cusp magnetic field. The resulting plasma fueling and cross-field diffusion is discussed.

  8. Increased plasma clearance rate of thyroxine despite decreased 5'-monodeiodination: study with a peroxisome proliferator in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Kaiser, C.A.; Seydoux, J.; Giacobino, J.P.; Girardier, L.; Burger, A.G.


    In euthyroid rats a 17-day treatment with nafenopin, a hypolipidemic agent and peroxisome proliferator, decreased serum total and free T4 concentrations to 32 +/- 5% and 62 +/- 8% (mean +/- SEM; n = 10), respectively, with no change in serum T3 and TSH concentrations. In methimazole-treated rats infused with 3 nmol T4/day/100 g BW, the nafenopin inhibitory effect was not significantly different from that in euthyroid rats. Nafenopin treatment had the following effects on peripheral T4 and T3 metabolism in euthyroid rats. The plasma clearance rate of T4 (PCR), which was measured by Alzet minipump infusion of tracer, was increased 2-fold (1.58 +/- 0.09 vs. 0.82 +/- 0.06 ml/h.100 g BW; P less than 0.001; n = 5), while the PCR of T3 was decreased (37.5 +/- 1.3 vs. 53.8 +/- 1.8; P less than 0.001; n = 5). The fecal clearance rate of radioactivity derived from T4 was increased 2-fold (1.93 +/- 0.10 vs. 0.77 +/- 0.07 ml/h.100 g BW), whereas the urinary clearance rate was not significantly modified. The 5'-deiodinase (5'D) activity, measured by deiodination of labeled rT3, was strongly inhibited in liver and kidney, not modified in brown fat and anterior pituitary, and increased in cerebral cortex. In methimazole-treated rats substituted with isopropyl-diiodothyronine only hepatic 5'D activity was decreased. It is concluded that the decrease in serum total and free T4, without alteration in serum T3 and TSH concentrations, resulting from nafenopin treatment is mainly due to changes in peripheral T4 and T3 metabolism, since it is also observed in T4-substituted animals. The increased PCR of T4 cannot be explained by an increase in deiodination activity, since the major 5'D pathways are inhibited after nafenopin treatment, and the urinary clearance rate is not modified. It can partly be explained by an increase in the fecal clearance rate of T4, which could be due to an increase in glucoronoconjugation.

  9. Effects of glucocorticoids on plasma levels of thyroid hormones (T4 and T3) and testicular activity in catfish, Clarias gariepinus during different phases of annual breeding cycle. (United States)

    Suchiang, P; Varkey, S; Gupta, B B P


    Effects of short-term administration of corticosterone and cortisol on plasma levels of thyroid hormones, gonado-somatic index and testicular histology have been reported in catfish, Clarias gariepinus during different phases of its breeding cycle. Corticosterone administration had no significant effect on plasma levels of T4, T3 and T3/T4 ratio, irrespective of doses and phases of breeding cycle. However, 5 microg dose of cortisol significantly increased plasma levels of T3 and the T3/T4 ratio during quiescent and regressive phases, while it significantly decreased plasma levels of T4 during progressive phase. During breeding phase, 2 microg and 5 microg doses of cortisol significantly decreased plasma levels of T4 and T3, respectively, while 5 microg dose of cortisol alone reduced T3/T4 ratio. Irrespective of phases of annual breeding cycle and doses, short-term administration of corticosterone and cortisol had no significant effect either on GSI or testicular histology. These findings suggest that corticosterone is ineffective in stimulating plasma levels of thyroid hormones, while cortisol, depending on dose and phase/season, may differentially increase, decrease or have no effect on plasma levels of thyroid hormones in C. gariepinus.

  10. Measuring free thyroxine levels in neonatal heel-prick samples

    NARCIS (Netherlands)

    Boelen, A.; Veen, M. van; Verkerk, P.H.; Diependaal, G.; Loeber, G.; Elvers, B.; Endert, E.


    The Dutch neonatal screening scheme for Congenital Hypothyroidism (CH) is primarily based on the determination of thyroxine (T4) in filter paper blood spots. In the lowest 5% of T4 values, thyroxine binding globulin (TBG) is measured in order to be able to correct for occasional low TBG levels. Howe

  11. [Thyroxine and triiodothyronine]. (United States)

    Pinchera, A; Ambrosino, N; Mammoli, C


    The value of measurements of serum thyroxine (T4) and triiodothyronine (T3) concentrations in the clinical evaluation of thyroid function is well established. In the present report the properties of the methods currently available for the assessment of circulating thyroid hormones are examined. Recent data indicate that results of measurements of serum T4 by radioimmunoassay (RIA) or by displacement analysis are qualitatively and quantitatively similar. Evidence has been provided from this and other laboratories that elevated or subnormal serum levels of total tt4 may be observed in several euthyroid physiologicmal serum levels of total T4 may be observed in several euthyroid physiological or pathological conditions associated with altered capacity of the thyroxine-binding protein; in these cases a normal free thyroxine index is usually found indicating its importance in the evaluation of thyroid function. Several physiological observations and the recent recognition of clinical conditions associated with changes in the T4/T3 ratio, justify the present interest in the measurement of serum T3. The advantages of RIA methods with respect to displacement techniques in the determination of this hormone are well documented. The AA. report here their experience with a simple RIA method for total T3, using a single Sephadex G25 column for extraction of T3 from serum and for separation of bound from free hormone. The mean (+/-SD) values of serum T3 found in 78 normal, 23 hyperthyroid and 25 hypothyroid subjects were as follows:160+/37ng/dl, 604+/195ng/dl and 35+/23ng/dl respectively. High values were found in 19 pregnant women at delivery (236+/29ng/dl), but not in 5 subjects on contraceptives (156+/42ng/dl). A relatively large variability is noted when normal values reported from different laboratories are compared. This may be related at least in part to geographical and/or ethnical factors, but methodolgical differences may also be involved. The normal range of

  12. 成年期甲状腺功能减退症大鼠额叶突触结合蛋白I表达及T4替代治疗作用%Expression of synaptotagmin I and effect of thyroxine treatment in the prefrontal cortex of adult hypothyroid rats

    Institute of Scientific and Technical Information of China (English)

    王茜; 杨会云; 王建月; 桂丽; 朱德发


    Objective To observe the expression of synaptotagmin I(syt I)protein in the prefrontal cortex of adult-onset hypothyroidism rats and the effects of replicated therapy in different doses of thyroid hormone on the syt I protein.Methods All 44 aduh male Sprague-Dawley rats were divided into 4 groups randomly according to their body mass:hypothyroidism group,routine dosage thyroxine treatment group,high dosage thyroxine treatment group and control group.The adult male Sprague-Dawley rats were replicated to the adult-onset hypothyroidism and treatment models with propyhhiouracil(PTU).The levels of serum T3,T4 were assayed by the radioimmunoassay method and the level of the syt I protein in the molecular layer,external granular layer,external pyramidal layer,internal granular layer and internal pyramidal layer in prefrontal cortex was analyzed by immunohistochemistry.Results In the hypothyroidism group,the levels of serum T3 and T4[(0.34±0.04),(43.01±2.95)nmol/L]were significantly lower than those in the control group[(0.65±0.15), (55.20±3.56)nmol/L, F value: 6.026,5.940,4.503,P0.05), and the level of the syt I protein in the molecular layer, external granular layer, external pyramidal layer, internal granular layer and internal pyramidal layer in prefrontal cortex showed a significant improvement of the syt I protein(0.027 ± 0.013,0.025 ± 0.009,0.022 ± 0.008,0.020 ± 0.010,0.033 ± 0.010), which were similar to that of the control group(F value: 0.094,2.208,2.467,0.350,0.693, all P>0.05). In the high dosage thyroxine thyroid hormone treatment group, the levels of serum T3 and T4[ (1.11 ± 0.10), (96.68 ± 6.42)nmoL/L] were higher than the control group(F value: 6.291,12.031, all P0.05). Conclusions The expression of the syt I protein in the prefrontal cortex of adult-onset hypothyroidism can be decreased, which can be reversed by routine dosage of thyroxine treatment.%目的 观察成年期甲状腺功能减退症(甲减)大鼠

  13. Developmental Triclosan Exposure Decreases Maternal and Offspring Thyroxine in Rats* (United States)

    Epidemiological and laboratory data have demonstrated that disruption of maternal thyroid hormones during fetal developmental may result in irreversible neurological consequences in offspring. In a short-term exposure paradigm, triclosan decreased systemic thyroxine (T4) concentr...

  14. Thyroxine mimetics

    Directory of Open Access Journals (Sweden)

    Randa F Salam


    Full Text Available Thyroid hormones influence heart rate, serum lipids, metabolic rate, body weight, and multiple aspects of lipid, carbohydrate, protein, and mineral metabolism. Although increased thyroid hormone levels can improve serum lipid profiles and reduce fat, these positive effects are counterbalanced by the harmful effects on the heart, muscle, and bone. Thus, attempts to use thyroid hormones for cholesterol-lowering and weight loss purposes have so far been limited. However, over the past decade, thyroid hormone analogs that are capable of uncoupling the beneficial effects from the deleterious effects have been developed. Such drugs could serve as powerful new tools to address two of the largest medical problems, namely atherosclerosis and obesity. Aggressive reduction in LDL-cholesterol by the use of statins is a cornerstone of preventive cardiovascular risk, but additional therapies to prevent atherosclerosis and its clinical sequelae are still needed. Thyromimetics selective for the liver or the thyroid hormone receptor isoform β1 constitute a novel approach to treat dyslipidemia. In preclinical studies, selective thyromimetics were clearly shown to reduce plasma cholesterol and protect from atherosclerosis through the upregulation of hepatic LDL receptor and promotion of the so-called reverse cholesterol transport. Notably, there is the first evidence from on-going clinical trials that selective thyromimetics may reduce plasma cholesterol in humans also. Most importantly, thyromimetics has a synergistic action when used in combination with 3-hydroxy-3-methylglutaryl CoA reductase inhibitors. Animal data have further suggested that thyromimetics might be useful in the treatment of obesity, hepatic steatosis, and atherosclerosis.

  15. Treating Hypothyroidism with Thyroxine/Triiodothyronine Combination Therapy in Denmark

    DEFF Research Database (Denmark)

    Michaelsson, Luba Freja; Medici, Bjarke Borregaard; la Cour, Jeppe Lerche


    BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) or desiccated thyroid] are still regarded as experime......BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) or desiccated thyroid] are still regarded...... after a patient published a book describing her experiences with hypothyroidism and treatment. OBJECTIVE: To investigate current Danish trends in the use of T4/T3 combination therapy. METHODS: We used an Internet-based questionnaire, distributed as a link via two Danish patient fora. Further...

  16. Thyroxine Level of Children with Cerebral Palsy

    Institute of Scientific and Technical Information of China (English)

    Zhang Jie


    Objective:To investigate the thyroxine level of Children with cerebral palsy so as to understand thd changes of their nevous endocrine. Methods:Radioimmunoassay was applied to 57 Children with cerebral palsy and 108 normal children.The serum level of tridothyronine(T3), thyroxine(T4)free tridothyronine(FT3),free thyroxin(FT4),and thyroid stimulating hormone(TSH) were measured for those children in the moming and and in condition without any food Rsults: (1)Chiidren with cerebral palsy all showed low T3 values.The difference of T3 value between CP children and norrmal children was significant (P<0.001). (2)Results from groups with difference ages:the CP toddler′s age group also showed low T4 and FT4 values The difference of T4 and FT4 values between the toddler′s age CP childrengroup and the toddler′s age normal children group tegted was significant (CP<0.01 for T4, P <0. 05 for FT4): Conclusion:The tlyroxine level of children with cerebral palsy showed lower values compared to normal children, especisly, the low T3 values were significant.

  17. The effect of phenobarbital on the metabolism and excretion of thyroxine in rats

    Energy Technology Data Exchange (ETDEWEB)

    McClain, R.M.; Levin, A.A.; Posch, R.; Downing, J.C.


    The effect of phenobarbital on thyroid function and the metabolism and biliary excretion of thyroxine in rats was determined. Phenobarbital, administered for 2 weeks at a dose of 100 mg/kg/day, resulted in an increase in hepatic and thyroid gland weights, decreased circulating levels of T4, T3 and rT3, and increased TSH levels in male and female rats. After 3 months of treatment liver and thyroid weights were still increased; however, hormone values were not as markedly affected indicating that the rats had partially compensated for the effect on thyroid function. In thyroidectomized rats the plasma clearance of thyroxine was increased with phenobarbital. In bile duct cannulated phenobarbital-treated male rats the hepatic uptake at 4 hr was markedly increased. Bile flow was increased and the 4-hr cumulative biliary excretion of administered radioactivity was increased by 42%. Most of the increase in the excretion (76%) was accounted for by an increase in the excretion of thyroxine-glucuronide in phenobarbital-treated rats. Hepatic thyroxine-glucuronyltransferase activity in phenobarbital-treated rats expressed as picomoles per milligram of protein was increased by 40%; enzyme activity per gram of liver was increased by about twofold which, coupled with increased hepatic weight, resulted in about a threefold increase in total hepatic thyroxine-glucuronyltransferase activity in phenobarbital-treated rats as compared to that of controls. Qualitatively similar effects on metabolism, excretion, and enzyme induction were noted in female rats; however, the magnitude of increase was less than that observed in male rats. It is concluded that the effect of phenobarbital on thyroid function in rats is primarily a result of its effects on the hepatic disposition of thyroid hormone.

  18. Triclosan Decreases Rat Thyroxine: Mode-of-Action, Developmental Susceptibility and Human Relevance (United States)

    Triclosan (TCS) decreases serum thyroxine (T4) in the rat. In vivo and in vitro approaches were used to address three uncertainties: by what mode-of-action (MOA) does TCS decrease T4; does TCS decrease T4 developmentally; and, are effects observed in rats relevant to humans? To t...

  19. In vitro fluorescence displacement investigation of thyroxine transport disruption by bisphenol A

    Institute of Scientific and Technical Information of China (English)

    Jie Cao; Liang-Hong Guo; Bin Wan; Yin Wei


    Bisphenol A (BPA) is a chemical with high production volume and wide applications in many industries.Although BPA is known as an endocrine disruptor, its toxic mechanisms have not been fully characterized.Due to its structural similarity to thyroid hormones thyroxine (T4) and triiodothyronine (T3), one possible mechanism of BPA toxicity is disruption of hormone transport by competitive binding with the transport proteins.In this study, the binding interactions of BPA, T4, and T3 with three thyroid hormone transport proteins, human serum albumin (HSA), transthyretin (TTR), and thyroxine-binding globulin (TBG) were investigated by fluorescence measurement.Using two site-specific fluorescence probes dansylamide and dansyl-L-proline, the binding constants of BPA with HSA at drug site I and site Ⅱ were determined as 2.90 × 104 and 3.14 × 104 L/mol, respectively.By monitoring the intrinsic fluorescence of tryptophan, a binding constant of 4.70 × 103 L/mol was obtained.Similarly, by employing 8-anilino-1-naphthalenesulfonic acid as fluorescence probe, the binding affinity of BPA with TTR and TBG was measured to be 3.10 × 105 and 5.90 × 105 L/mol, respectively.In general, BPA showed lower binding affinity with the proteins than T3 did, and even lower affinity than T4.Using these binding constants, the amount of BPA which would bind to the transport proteins in human plasma was estimated.These results suggest that the concentrations of BPA commonly found in human plasma are probably not high enough to interfere with T4 transport.

  20. The effects of thyroxine or a GnRH analogue on thyroid hormone deiodination in the olfactory epithelium and retina of rainbow trout, Oncorhynchus mykiss, and sockeye salmon, Oncorhynchus nerka. (United States)

    Plate, E M; Adams, B A; Allison, W T; Martens, G; Hawryshyn, C W; Eales, J G


    Using low (0.5nM) substrate levels we determined the activities of thyroxine (T4) outer-ring deiodination (ORD), T4 inner-ring deiodination (T4IRD) and 3,5,3(')-triiodothyronine (T3) IRD activities in the olfactory epithelium (OLF) and retina (RET) of laboratory-held immature 1-year-old rainbow trout and immature 2.5-year-old sockeye salmon. In both species all three deiodination activities were detected in OLF and RET. For OLF, no particular pathway predominated and activities were similar to those of brain. For RET, T3IRD activity was greater than T4ORD activity and in sockeye RET T3IRD activity exceeded that of liver. Trout immersion for 6 weeks in 100ppm T4 increased plasma T4 levels 3-fold and plasma T3 levels by 50% and caused the anticipated autoregulatory responses in brain and liver deiodination ( downward arrow T4ORD, upward arrow T4IRD, and upward arrow T3IRD); OLF deiodination and RET T4ORD activity were unaltered but RET T4IRD and T3IRD activities increased dramatically. Two injections of a GnRH analogue (20 microgkg(-1)) into sockeye increased plasma T3 levels but not T4 levels and decreased RET T4IRD and T3IRD activities without changing liver, brain, or OLF deiodination. We conclude that in salmonids the main TH deiodination pathways occur in OLF but show no regulation by T4 or GnRH. In contrast, T3IRD activity predominates in RET and can be regulated by T4 and GnRH, suggesting that for RET plasma may be the major T3 source. These findings have implications for thyroidal regulation of sensory functions during salmonid diadromous migrations.

  1. Effects of growth hormone and thyroxine replacement therapy on insulin signaling in Ames dwarf mice. (United States)

    Louis, Audreen; Bartke, Andrzej; Masternak, Michal M


    Ames dwarf (Prop1(df), df/df) mice lack growth hormone (GH), prolactin, and thyrotropin and live remarkably longer than their normal siblings. Significance of reduced activity of the somatotropic and thyroid axes during development and adulthood on longevity are unknown. Because enhanced insulin sensitivity and reduced insulin levels are among likely mechanisms responsible for increased longevity in these mutants, we compared the effects of GH and thyroxine (T4) replacement on various parameters related to insulin signaling in young and old male df/df mice. The results suggest that altered plasma adiponectin and insulin-like growth factor-1 (IGF-1) and hepatic IGF-1, insulin receptor (IR), IR substrate-1, peroxisome proliferator-activated receptor (PPAR) gamma, and PPARgamma coactivator-1 alpha may contribute to increased insulin sensitivity in Ames dwarfs. The stimulatory effect of GH and T4 treatment on plasma insulin and inhibitory effect on expression of hepatic glucose transporter-2 were greater in old than in young dwarfs. These results indicate that GH and T4 treatment has differential impact on insulin signaling during development and adulthood.

  2. [Lugol's solution and thyroid gland activity in cattle. Determination of the total thyroxine in blood plasma as a method for evaluating thyroid gland activity]. (United States)

    Braun, U; Leidl, W


    The aim of the present investigations was to examine if an intrauterine treatment with Lugol's solution in cows influences the activity of the thyroid gland. The thyrotropin-stimulation test was used to evaluate the function of the thyroid gland. An injection of 10 I. U. thyreotropin induced within 3 hours an increase of the T4 blood concentrations which reached maximal values 9 hours after the treatment and thereafter decreased again. Thyreotropin concentrations increasing from 5 to 30 I. U. led to a dose-dependent increase of the T4 blood concentrations. The T4 values obtained by 40 i. U. thyreotropin were lower than that induced with 30 I. U. of the hormone. The T4 concentrations increased stronger and remained elevated longer in cows pretreated intrauterine with Lugol's solution than in untreated control cows. The experiments demonstrated that an intrauterine infusion of Lugol's solution may result in an increased activity of the thyroid gland.

  3. t4 Workshop Report (United States)

    Silbergeld, Ellen K.; Contreras, Elizabeth Q.; Hartung, Thomas; Hirsch, Cordula; Hogberg, Helena; Jachak, Ashish C.; Jordan, William; Landsiedel, Robert; Morris, Jeffery; Patri, Anil; Pounds, Joel G.; de Vizcaya Ruiz, Andrea; Shvedova, Anna; Tanguay, Robert; Tatarazako, Norihasa; van Vliet, Erwin; Walker, Nigel J.; Wiesner, Mark; Wilcox, Neil; Zurlo, Joanne


    Summary In October 2010, a group of experts met as part of the transatlantic think tank for toxicology (t4) to exchange ideas about the current status and future of safety testing of nanomaterials. At present, there is no widely accepted path forward to assure appropriate and effective hazard identification for engineered nanomaterials. The group discussed needs for characterization of nanomaterials and identified testing protocols that incorporate the use of innovative alternative whole models such as zebrafish or C. elegans, as well as in vitro or alternative methods to examine specific functional pathways and modes of action. The group proposed elements of a potential testing scheme for nanomaterials that works towards an integrated testing strategy, incorporating the goals of the NRC report Toxicity Testing in the 21st Century: A Vision and a Strategy by focusing on pathways of toxic response, and utilizing an evidence-based strategy for developing the knowledge base for safety assessment. Finally, the group recommended that a reliable, open, curated database be developed that interfaces with existing databases to enable sharing of information. PMID:21993959

  4. Use of dietary thyroxine as an alternate molting procedure in spent turkey breeder hens. (United States)

    Gulde, V A L; Renema, R; Bédécarrats, G Y


    In the turkey industry, molting is traditionally achieved by reducing photoperiod and withdrawing feed and water for several days. Although it is the most effective method, this practice is discouraged in Canada and alternative strategies need to be established. Thyroid hormone levels naturally change during molt, and dietary thyroxine (T4) supplementation was previously shown to induce molt in chickens. This study aimed at evaluating the effectiveness of supplemental dietary T4 in inducing molt in spent turkey breeder hens. One hundred twenty 75-wk-old hens were randomly divided into 4 groups (5 floor pens/replicates, 5 hens each) with the control group kept under a 14-h photoperiod and fed a breeder's diet throughout, whereas hens from the 3 other groups were supplemented with 40 ppm (45.76 mg/kg) T4 for 10 d. One treatment group was maintained under 14 h of light and fed a breeder's diet, whereas the 2 others were subjected to a drop in photoperiod to 6 h during or after supplementation and then were fed a maintenance diet. Egg production, feed intake, BW, molt, and plasma levels of T4, prolactin, and luteinizing hormone were measured. All treated hens ceased laying by d 20; however, several individuals spontaneously returned to lay when left on 14 h of light, suggesting incomplete involution of the reproductive tract. Supplementation significantly reduced feed consumption and induced rapid BW loss. All hens returned to their initial weight by the end of the experiment. Most treated hens initiated molt by d 8 of supplementation and all completed molt by d 37. Plasma T4 in treated hens increased significantly by d 3 (P dropping the photoperiod was necessary to completely reset the reproductive system.

  5. Monocarboxylate transporter 8 deficiency: altered thyroid morphology and persistent high triiodothyronine/thyroxine ratio after thyroidectomy. (United States)

    Wirth, Eva K; Sheu, Sien-Yi; Chiu-Ugalde, Jazmin; Sapin, Remy; Klein, Marc O; Mossbrugger, Ilona; Quintanilla-Martinez, Leticia; de Angelis, Martin Hrabĕ; Krude, Heiko; Riebel, Thomas; Rothe, Karin; Köhrle, Josef; Schmid, Kurt W; Schweizer, Ulrich; Grüters, Annette


    Thyroid hormone transport across the plasma membrane depends on transmembrane transport proteins, including monocarboxylate transporter 8 (MCT8). Mutations in MCT8 (or SLC16A2) lead to a severe form of X-linked psychomotor retardation, which is characterised by elevated plasma triiodothyronine (T(3)) and low/normal thyroxine (T(4)). MCT8 contributes to hormone release from the thyroid gland. To characterise the potential impact of MCT8-deficiency on thyroid morphology in a patient and in Mct8-deficient mice. Thyroid morphology in a patient carrying the A224V mutation was followed by ultrasound imaging for over 10 years. After thyroidectomy, a histopathological analysis was carried out. The findings were compared with histological analyses of mouse thyroids from the Mct8(-/y) model. We show that an inactivating mutation in MCT8 leads to a unique, progressive thyroid follicular pathology in a patient. After thyroidectomy, histological analysis revealed gross morphological changes, including several hyperplastic nodules, microfollicular areas with stromal fibrosis and a small focus of microfollicular structures with nuclear features reminiscent of papillary thyroid carcinoma (PTC). These findings are supported by an Mct8-null mouse model in which we found massive papillary hyperplasia in 6- to 12-month-old mice and nuclear features consistent with PTC in almost 2-year-old animals. After complete thyroidectomy and substitution with levothyroxine (l-T(4)), the preoperative, inadequately low T(4) and free T(4) remained, while increasing the l-T(4) dosage led to T(3) serum concentrations above the normal range. Our results implicate peripheral deiodination in the peculiar hormonal constellation of MCT8-deficient patients. Other MCT8-deficient patients should be closely monitored for potential thyroid abnormalities.

  6. The two triiodothyronines (T3 and rT3). Thyroid biosynthesis of T3 and rT3 and peripheral metabolism of thyroxine (author's transl). (United States)

    Roche, J; Michel, R


    Thirty per cent of the iodine in thyroglobulin is present as iodothyronines. L-thyroxine (T4) represents 90-95% of hormonal iodine, 3,5,3'-triodo-L-thyronine (T3) contains at the most two per cent of it, 3,3'5'-triodo-L-thyronine (rT3) even less, as well as traces of 3,3'-diodo-L-thyronine. The plasma concentration of T4 is about 8 microgram per 100 ml, in the case of T3 it is 120 ng and 25 ng for rT3. The cell nucleus preferentially binds T3 and rT3 and there are also some specific mitochondrial proteins which possess a high affinity for T3. L-thyroxine is dehalogenated peripherically to T3, to take care of most of the requirements in T3. The enrichment of the plasma in rT3 has been shown to occur under various experimental and pathological conditoins. The blood level of T3 varies in inverse ratio to the level of rT3 and it shows that the peripheral formation of one is compensated for by the other. The excess of the prehormone T4 is metabolised as 3,5,3',5'-tetraiodothyroacetic acid (TetrAc); its level in the blood varies in the same way as the level of T3, in particular it decreases during starvation.

  7. 21 CFR 862.1685 - Thyroxine-binding globulin test system. (United States)


    ... protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroxine-binding globulin test system. 862.1685 Section 862.1685 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  8. Low serum free thyroxine level in a girl with McCune-Albright syndrome. (United States)

    Roosimaa, Mart; Pajuväli, Anett; Peet, Aleksandr; Tillmann, Vallo


    A 17-year-old girl with McCune-Albright syndrome (MAS) was suspected of having central hypothyroidism based on an inappropriately normal thyroid-stimulating hormone (TSH) and low free thyroxine (fT4). She was clinically euthyroid and her pituitary appeared normal on MRI. Treatment of hypothyroidism with levothyroxine resulted in suppression of TSH with a low fT4 and high free triiodothyronine (fT3) concentration and hence iatrogenic hyperthyroidism was diagnosed. After discontinuation of levothyroxine, the TSH and fT3 normalised while fT4 remained low. Increased conversion of thyroxine (T4) to triiodothyronine (T3) can be part of MAS. Therefore, fT3 and fT4 should both be measured when evaluating thyroid function in patients with MAS.

  9. Congenital hypothyroidism, as studied in rats. Crucial role of maternal thyroxine but not of 3,5,3'-triiodothyronine in the protection of the fetal brain. (United States)

    Calvo, R; Obregón, M J; Ruiz de Oña, C; Escobar del Rey, F; Morreale de Escobar, G


    To study the protective effects of maternal thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in congenital hypothyroidism, we gave pregnant rats methimazole (MMI), an antithyroid drug that crosses the placenta, and infused them with three different doses of T4 or T3. The concentrations of both T4 and T3 were determined in maternal and fetal plasma and tissues (obtained near term) by specific RIAs. Several thyroid hormone-dependent biological end-points were also measured. MMI treatment resulted in marked fetal T4 and T3 deficiency. Infusion of T4 into the mothers increased both these pools in a dose-dependent fashion. There was a preferential increase of T3 in the fetal brain. Thus, with a T4 dose maintaining maternal euthyroidism, fetal brain T3 reached normal values, although fetal plasma T4 was 40% of normal and plasma TSH was high. The infusion of T3 pool into the mothers increased the total fetal extrathyroidal T3 pool in a dose-dependent fashion. The fetal T4 pools were not increased, however, and this deprived the fetal brain (and possibly the pituitary) of local generation of T3 from T4. As a consequence, fetal brain T3 deficiency was not mitigated even when dams were infused with a toxic dose of T3. The results show that (a) there is a preferential protection of the brain of the hypothyroid fetus from T3 deficiency; (b) maternal T4, but not T3, plays a crucial role in this protection, and (c) any condition which lowers maternal T4 (including treatment with T3) is potentially harmful for the brain of a hypothyroid fetus. Recent confirmation of transplacental passage of T4 in women at term suggests that present results are relevant for human fetuses with impairment of thyroid function. Finding signs of hypothyroidism at birth does not necessarily mean that the brain was unprotected in utero, provided maternal T4 is normal. It is crucial to realize that maintainance of maternal "euthyroidism" is not sufficient, as despite hypothyroxinemia, the mothers may be

  10. Role of Thyroxine in Space-Developed Jellyfish (United States)

    Spangenberg, Dorothy B.


    The Aurelia Metamorphosis Test System was previously used to determine the effects of the space environment on the development and behavior of tiny (1-2 mm) jellyfish ephyrae during the SLS-1 and IML-2 missions. Results from the SLS-1 experiment included the discovery that statolith numbers were significantly reduced in Earth-formed ephyrae flown for nine days in space as compared with ground-based controls. In addition, upon return to Earth, six times more ephyrae which had developed in space than those developed on Earth had pulsing abnormalities, indicating that either these animals did not form their neuromuscular structures normally while in space or they were unable to adapt to the Ig environment upon return to Earth. The metamorphosis process, which enables the formation of ephyrae from polyps is influenced by a hormone, Jf-T4 Oellyfish thyroxine) which is synthesized following iodine administration. Two groups of polyps in space, however, formed ephyrae without iodine administration indicating that Jf-T4 synthesis, utilization, or excretion was different in. the ephyrae. Increased synthesis or build-up in the media of the hormone may also be linked to the increased demineralization of statoliths found in space-exposed ephyrae. In previous experiments, we found that externally administered thyroxine causes increased demineralization of statoliths on Earth. Abnormal pulsina in ephyrae following return to Earth during the SLS-1 mission may also be traced to increased Jf-T4 levels. Thyroxine is known to be important to the normal development and function of the nervous system, heart, and skeletal muscles in higher animals. For this third Jellyfish-in-Space experiment, we proposed to quantitate the levels of Jf- T4 and of T4 receptors in space-developed ephyrae and media and to compare these levels with those of animals developing and at Ig in space and on Earth. We expected to be able to determine whether Jf-T4 synthesis and/or secretion is different in space

  11. Thyroxine modifies the effects of growth hormone in Ames dwarf mice


    Do, Andrew; Menon, Vinal; Zhi, Xu; Gesing, Adam; Wiesenborn, Denise S.; Spong, Adam; Sun, Liou; Bartke, Andrzej; Masternak, Michal M.


    Ames dwarf (df/df) mice lack growth hormone (GH), thyroid stimulating hormone and prolactin. Treatment of juvenile df/df mice with GH alone stimulates somatic growth, reduces insulin sensitivity and shortens lifespan. Early‐life treatment with thyroxine (T4) alone produces modest growth stimulation but does not affect longevity. In this study, we examined the effects of treatment of juvenile Ames dwarf mice with a combination of GH + T4 and compared them to the effects of GH alone. Treatment ...

  12. [Role of ultrasensitive TSH assay and ultrarapid total thyroxine assay in the thyroid studies]. (United States)

    Fragu, P; Comoy, E; Noël, M; Lounis, M; Patois, E; Parmentier, C


    The diagnostic value of high sensitivity thyrotrophin assay (HS-TSH) and that of ultra-short determination of total thyroxine (T4) by fluorescence polarization (T4-TDX) were evaluated in 284 patients (29 hyperthyroid, 137 euthyroid without treatment and 118 under substitutive therapy). After comparing the clinician's first impression with the results of these laboratory tests the proportion of correctly classified untreated euthyroid patients was the same with T4-TDX as with HS-TSH (90%). In contrast, this proportion in hyperthyroid patients was about twice as low with HS-TSH (23%) as with T4-TDX (42%). While HS-TSH gives a better diagnostic evaluation, T4-TDX is an excellent indicator of the degree of hyperthyroidism. In patients under suppressive therapy HS-TSH and T4-TDX provide a better evaluation of therapeutic effectiveness.

  13. A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents (United States)

    Svendstrup, Mathilde; Ohrt, Johanne Dam; Dahl, Maria; Fonvig, Cilius Esmann; Hollensted, Mette; Have, Christian Theil; Kadarmideen, Haja N.; Pedersen, Oluf; Hansen, Torben; Holm, Jens-Christian; Grarup, Niels


    Background Hypothyroidism is associated with obesity, and thyroid hormones are involved in the regulation of body composition, including fat mass. Genome-wide association studies (GWAS) in adults have identified 19 and 6 loci associated with plasma concentrations of thyroid stimulating hormone (TSH) and free thyroxine (fT4), respectively. Objective This study aimed to identify and characterize genetic variants associated with circulating TSH and fT4 in Danish children and adolescents and to examine whether these variants associate with obesity. Methods Genome-wide association analyses of imputed genotype data with fasting plasma concentrations of TSH and fT4 from a population-based sample of Danish children, adolescents, and young adults, and a group of children, adolescents, and young adults with overweight and obesity were performed (N = 1,764, mean age = 12.0 years [range 2.5−24.7]). Replication was performed in additional comparable samples (N = 2,097, mean age = 11.8 years [1.2−22.8]). Meta-analyses, using linear additive fixed-effect models, were performed on the results of the discovery and replication analyses. Results No novel loci associated with TSH or fT4 were identified. Four loci previously associated with TSH in adults were confirmed in this study population (PDE10A (rs2983511: β = 0.112SD, p = 4.8 ∙ 10−16), FOXE1 (rs7847663: β = 0.223SD, p = 1.5 ∙ 10−20), NR3C2 (rs9968300: β = 0.194SD), p = 2.4 ∙ 10−11), VEGFA (rs2396083: β = 0.088SD, p = 2.2 ∙ 10−10)). Effect sizes of variants known to associate with TSH or fT4 in adults showed a similar direction of effect in our cohort of children and adolescents, 11 of which were associated with TSH or fT4 in our study (padolescents, four loci previously associated with plasma TSH concentrations in adults, were associated with plasma TSH concentrations in children, suggesting comparable genetic determinants of thyroid function in adults and children. PMID:28333968

  14. Glucuronidation of thyroxine in human liver, jejunum, and kidney microsomes. (United States)

    Yamanaka, Hiroyuki; Nakajima, Miki; Katoh, Miki; Yokoi, Tsuyoshi


    Glucuronidation of thyroxine is a major metabolic pathway facilitating its excretion. In this study, we characterized the glucuronidation of thyroxine in human liver, jejunum, and kidney microsomes, and identified human UDP-glucuronosyltransferase (UGT) isoforms involved in the activity. Human jejunum microsomes showed a lower K(m) value (24.2 microM) than human liver (85.9 microM) and kidney (53.3 microM) microsomes did. Human kidney microsomes showed a lower V(max) value (22.6 pmol/min/mg) than human liver (133.4 pmol/min/mg) and jejunum (184.6 pmol/min/mg) microsomes did. By scaling-up, the in vivo clearances in liver, intestine, and kidney were estimated to be 1440, 702, and 79 microl/min/kg body weight, respectively. Recombinant human UGT1A8 (108.7 pmol/min/unit), UGT1A3 (91.6 pmol/min/unit), and UGT1A10 (47.3 pmol/min/unit) showed high, and UGT1A1 (26.0 pmol/min/unit) showed moderate thyroxine glucuronosyltransferase activity. The thyroxine glucuronosyltransferase activity in microsomes from 12 human livers was significantly correlated with bilirubin O-glucuronosyltransferase (r = 0.855, p microsomes was mainly catalyzed by UGT1A8 and UGT1A10 and to a lesser extent by UGT1A1, and the activity in human kidney microsomes was mainly catalyzed by UGT1A7, UGT1A9, and UGT1A10. The changes of activities of these UGT1A isoforms via inhibition and induction by administered drugs as well as genetic polymorphisms may be a causal factor of interindividual differences in the plasma thyroxine concentration.

  15. Radioimmunoassay of thyroxine in saliva

    Energy Technology Data Exchange (ETDEWEB)

    Putz, Z.; Vanuga, A.; Veleminsky, J. (Institute of Clinical Endocrinology, Lubochna (Czechoslovakia))


    A simple radioimmunoassay (RIA) for thyroxine (T/sub 4/) in saliva has been described. Fifty euthyroid control subjects, 14 euthyroid pregnant women, 23 thyreotoxic and 10 hypothyroid patients were examined. Serum T/sub 3/, T/sub 4/, thyroxine binding globulin (TBG) and TSH were measured simultaneously. The mean level of T/sub 4/ in saliva in controls was 1.10 +- 0.07 nmol/l. There was a good correlation between the saliva and serum T/sub 4/ concentrations (r = 0.74) and between saliva T/sub 4/ values and the T/sub 4//TBG ratio (r = 0.83). The saliva T/sub 4/ levels, like serum free T/sub 4/, were not dependent on fluctuations of serum TBG concentrations. In euthyroid pregnant women, saliva T/sub 4/ levels were within the normal range while the serum T/sub 4/ and TBG were increased. There was a good agreement of saliva T/sub 4/ values with the functional state of the thyroid. Thus, the RIA of saliva T/sub 4/ could replace the laborious determination of serum free T/sub 4/. It can especially be useful in instances with abnormal values of TBG, as it is in pregnancy, in congenital deficiency of serum TBG or in subjects with hereditary elevated TBG levels.


    Studies demonstrate that exposure to 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) and 2,2',4,4',5,5'· hexachlorobiphenyl (PCB 153) decrease serum thyroxine (T4)levels in laboratory animals 1,2,3. The T4 decrease in rodents is thought to occur through the induction of UDP-glucurono...

  17. Thyroxin Is Useful to Improve Sperm Motility

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    Mendeluk Gabriela Ruth


    Full Text Available Background The aim of this study was to evaluate the non-genomic action of thyroxin on sperm kinetic and its probable use to improve sperm recovery after applying an en- richment method like “swim-up” in comparison with the available one, pentoxifylline. Materials and Methods This is an experimental study. A total of 50 patients were re- cruited, followed by infertility consultation. Conventional sperm assays were performed according to World Health Organization criteria-2010 (WHO-2010. A Computer Aided Semen Analysis System was employed to assess kinetic parameters and concentrations. Number of the motile sperm recovered after preparation technique was calculated. Results Addition of T4 (0.002 µg/ml to semen samples increased hypermotility at 20 minutes (control: 14.18 ± 5.1% vs. 17.66 ± 8.88%, P<0.03, data expressed as mean ± SD and remained unchanged after 40 minutes. Significant differences were found in the motile sperm recovered after swim-up (control: 8.93×106 ± 9.52× 06vs. 17.20×106 ± 21.16×106, P<0.03, achieving all of the tested samples a desirable threshold value for artificial insemination outcome, while adding pentoxifylline increased the number of recovered sperm after swim-up in 60% of the studied cases. No synergism between two treatments could be determined. Conclusion We propose a new physiological tool to artificially improve insemination. The discussion opens windows to investigate unknown pathways involved in sperm ca- pacitation and gives innovative arguments to better understand infertility mechanisms.

  18. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Boberg, Julie; Vinggaard, Anne Marie


    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T4) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout...... gestation and lactation. Total T4 serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T4 in dams, but no significant effects on T4 levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure...... through maternal milk, a second study using direct per oral pup exposure from postnatal day 3–16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T4 reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing...

  19. Free Thyroxine During Early Pregnancy and Risk for Gestational Diabetes.

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    James E Haddow

    Full Text Available Several studies have now reported associations between gestational diabetes mellitus (GDM and low free thyroxine (fT4 during the second and third trimesters, but not in the first trimester. The present study further examines relationships between low fT4, maternal weight, and GDM among women in the FaSTER (First and Second Trimester Evaluation of Risk trial, in an effort to determine the extent to which thyroid hormones might contribute to causality. The FaSTER cohort includes 9351 singleton, euthyroid women; 272 of these women were subsequently classified as having GDM. Thyrotropin (TSH, fT4, and thyroid antibodies were measured at 11-14 weeks' gestation (first trimester and 15-18.9 weeks' gestation (second trimester. An earlier report of this cohort documented an inverse relationship between fT4 in the second trimester and maternal weight. In the current analysis, women with GDM were significantly older (32 vs. 28 years and weighed more (75 vs. 64.5 kg. Maternal weight and age (but not TSH were significantly associated univariately with fT4 (dependent variable, in the order listed. Second trimester fT4 odds ratios (OR for GDM were 2.06 [95% CI 1.37-3.09] (unadjusted; and 1.89 [95% CI 1.26-2.84] (adjusted. First trimester odds ratios were not significant: OR 1.45 [95%CI 0.97-2.16] (unadjusted and 1.11 [95% CI 0.74-1.62] (adjusted. The second trimester fT4/GDM relationship thus appeared to strengthen as gestation progressed. In FaSTER, high maternal weight was associated with both low fT4 and a higher GDM rate in the second trimester. Peripheral deiodinase activity is known to increase with high caloric intake (represented by high weight. We speculate that weight-related low fT4 (the metabolically inactive prohormone is a marker for deiodinase activity, serving as a substrate for conversion of fT4 to free triiodothyronine (fT3, the active hormone responsible for glucose-related metabolic activity.

  20. Thyroid function in children and adolescents with Hashimoto's thyroiditis after l-thyroxine discontinuation. (United States)

    Radetti, Giorgio; Salerno, Mariacarolina; Guzzetti, Chiara; Cappa, Marco; Corrias, Andrea; Cassio, Alessandra; Cesaretti, Graziano; Gastaldi, Roberto; Rotondi, Mario; Lupi, Fiorenzo; Fanolla, Antonio; Weber, Giovanna; Loche, Sandro


    Thyroid function may recover in patients with Hashimoto's thyroiditis (HT). To investigate thyroid function and the need to resume l-thyroxine treatment after its discontinuation. Nine Italian pediatric endocrinology centers. 148 children and adolescents (25 m and 123 f) with HT on treatment with l-thyroxine for at least one year. Treatment was discontinued in all patients, and serum TSH and fT4 concentrations were measured at the time of treatment discontinuation and then after 2, 6, 12 and 24 months. Therapy with l-thyroxine was re-instituted when TSH rose >10 U/L and/or fT4 was below the normal range. The patients were followed up when TSH concentrations were between 5 and 10 U/L and fT4 was in the normal range. At baseline, TSH was in the normal range in 139 patients, and was between 5 and 10 U/L in 9 patients. Treatment was re-instituted after 2 months in 37 (25.5%) patients, after 6 months in 13 patients (6.99%), after 12 months in 12 patients (8.6%), and after 24 months in an additional 3 patients (3.1%). At 24 months, 34 patients (34.3%) still required no treatment. TSH concentration >10 U/L at the time of diagnosis was the only predictive factor for the deterioration of thyroid function after l-thyroxine discontinuation. This study confirms that not all children with HT need life-long therapy with l-thyroxine, and the discontinuation of treatment in patients with a TSH level L at the time of diagnosis should be considered. © 2017 The authors.

  1. Thyroid function in children and adolescents with Hashimoto’s thyroiditis after l-thyroxine discontinuation

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    Giorgio Radetti


    Full Text Available Objective: Thyroid function may recover in patients with Hashimoto’s thyroiditis (HT. Design: To investigate thyroid function and the need to resume l-thyroxine treatment after its discontinuation. Setting: Nine Italian pediatric endocrinology centers. Patients: 148 children and adolescents (25 m and 123 f with HT on treatment with l-thyroxine for at least one year. Intervention and main outcome measure: Treatment was discontinued in all patients, and serum TSH and fT4 concentrations were measured at the time of treatment discontinuation and then after 2, 6, 12 and 24 months. Therapy with l-thyroxine was re-instituted when TSH rose >10 U/L and/or fT4 was below the normal range. The patients were followed up when TSH concentrations were between 5 and 10 U/L and fT4 was in the normal range. Results: At baseline, TSH was in the normal range in 139 patients, and was between 5 and 10 U/L in 9 patients. Treatment was re-instituted after 2 months in 37 (25.5% patients, after 6 months in 13 patients (6.99%, after 12 months in 12 patients (8.6%, and after 24 months in an additional 3 patients (3.1%. At 24 months, 34 patients (34.3% still required no treatment. TSH concentration >10 U/L at the time of diagnosis was the only predictive factor for the deterioration of thyroid function after l-thyroxine discontinuation. Conclusions: This study confirms that not all children with HT need life-long therapy with l-thyroxine, and the discontinuation of treatment in patients with a TSH level <10 U/L at the time of diagnosis should be considered.

  2. Erythropoietin, testosterone, and thyroxine in the erythropoietic response of the snake, Xenochrophis piscator. (United States)

    Pati, A K; Thapliyal, J P


    The erythropoietic response of snakes was examined after injecting human urinary erythropoietin (Ep), testosterone propionate (TP), and L-thyroxine (T4), separately and in combinations, into starved ophids. The effect of starvation was reflected by a decrease in the number of erythrocytes, a fall in hemoglobin concentration, and a decline in hematocrit. Statistically significant elevation of erythrocyte number, hemoglobin concentration, and hematocrit was observed at 24 hr following the administration of Ep + T4, and Ep + TP + T4 into starved ophids. The erythrocyte number was also increased by T4 treatment at 24 hr. Furthermore, while T4 and Ep individually increased the red blood cell number at 168 hr, T4, TP + T4, and Ep + TP + T4 elevated the hemoglobin concentration and Ep + T4 and Ep + TP + T4 increased the hematocrit value. It is suggested that the influence of any one of the hormones utilized in the present study on blood morphology of fasted snakes depends to a greater extent on the presence or absence of the other hormone(s).

  3. [Evaluation of the diagnostic power of 3 methods for assaying free T4. Results in the diagnostic strategy of hyperthyroidism]. (United States)

    Fragu, P; Noel, M; Patois, E; Delarue, J C; Paugam-Capelle, J; Parmentier, C


    The free thyroxin (FT4) tests of Amersham, Clinical Assay and Corning Medical were evaluated in 240 patients who were suspected of hyperthyroidism. The diagnostic performances of the Corning method were of less value while those of the other methods were equivalent to that obtained with the free thyroxin index for an average cost reduced. Furthermore our results show that T3 determination is better than T4 determination in patients who remained doubtful after FT4. However the development of ultra-short methods of measurement of total thyroid hormone blood levels using fluorescence polarization could lead to reconsider the diagnostic strategy of hyperthyroidism.

  4. Effect of short-term thyroxine administration on energy metabolism and mitochondrial efficiency in humans.

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    Darcy L Johannsen

    Full Text Available The physiologic effects of triiodothyronine (T3 on metabolic rate are well-documented; however, the effects of thyroxine (T4 are less clear despite its wide-spread use to treat thyroid-related disorders and other non-thyroidal conditions. Here, we investigated the effects of acute (3-day T4 supplementation on energy expenditure at rest and during incremental exercise. Furthermore, we used a combination of in situ and in vitro approaches to measure skeletal muscle metabolism before and after T4 treatment. Ten healthy, euthyroid males were given 200 µg T4 (levothyroxine per day for 3 days. Energy expenditure was measured at rest and during exercise by indirect calorimetry, and skeletal muscle mitochondrial function was assessed by in situ ATP flux ((31P MRS and in vitro respiratory control ratio (RCR, state 3/state 4 rate of oxygen uptake using a Clark-type electrode before and after acute T4 treatment. Thyroxine had a subtle effect on resting metabolic rate, increasing it by 4% (p = 0.059 without a change in resting ATP demand (i.e., ATP flux of the vastus lateralis. Exercise efficiency did not change with T4 treatment. The maximal capacity to produce ATP (state 3 respiration and the coupled state of the mitochondria (RCR were reduced by approximately 30% with T4 (p = 0.057 and p = 0.04, respectively. Together, the results suggest that T4, although less metabolically active than T3, reduces skeletal muscle efficiency and modestly increases resting metabolism even after short-term supplementation. Our findings may be clinically relevant given the expanding application of T4 to treat non-thyroidal conditions such as obesity and weight loss.

  5. Recovery following Thyroxine Treatment Withdrawal, but Not Propylthiouracil, Averts In Vivo and Ex Vivo Thyroxine-Provoked Cardiac Complications in Adult FVB/N Mice

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    Nancy S. Saad


    Full Text Available Persistent cardiovascular pathology has been described in hyperthyroid patients even with effective antithyroid treatment. Here, we studied the effect of a well-known antithyroid drug, propylthiouracil (PTU; 20 mg/kg/day, on thyroxine (T4; 500 µg/kg/day-induced increase in blood pressure (BP, cardiac hypertrophy, and altered responses of the contractile myocardium both in vivo and ex vivo after 2 weeks of treatment. Furthermore, the potential recovery through 2 weeks of T4 treatment discontinuation was also investigated. PTU and T4 recovery partially reduced the T4-prompted increase in BP. Alternatively, PTU significantly improved the in vivo left ventricular (LV function with no considerable effects on cardiac hypertrophy or ex vivo right ventricular (RV contractile alterations subsequent to T4 treatment. Conversely, T4 recovery considerably enhanced the T4-provoked cardiac changes both in vivo and ex vivo. Altogether, our data is in agreement with the proposal that hyperthyroidism-induced cardiovascular pathology could persevere even with antithyroid treatments, such as PTU. However, this cannot be generalized and further investigation with different antithyroid treatments should be executed. Moreover, we reveal that recovery following experimental hyperthyroidism could potentially ameliorate cardiac function and decrease the risk for additional cardiac complications, yet, this appears to be model-dependent and should be cautiously construed.

  6. Dyslipidemia in subclinical hypothyroidism and the effect of thyroxine on lipid profile

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    Ajay Asranna


    Full Text Available Introduction: Subclinical hypothyroidism (SH has a prevalence between 4% and 10.5% in various studies. The burden of SH in India is expected to increase with increasing iodine sufficiency. Studies have shown conflicting results concerning not only the degree of lipid changes in SH but also the effect of thyroxine substitution therapy. Indian studies on dyslipidemia in SH and the effect of thyroxine on lipid profile are currently lacking. Aims and Objectives: (1 To assess the association of SH and lipid profile. (2 To quantify the effect of thyroxine treatment on lipid profile. Materials and Methods: About 54 patients who were detected to have SH were compared with 56 healthy controls. Thyroid stimulating hormone (TSH, free T3, free T4, anti thyroperoxidase (TPO antibodies, total cholesterol, high density lipoprotein (HDL cholesterol, low density lipoprotein (LDL cholesterol, Very low density lipoprotein (VLDL cholesterol, serum triglycerides were measured in all the patients after an overnight fast. Selected patients were started on thyroxine replacement. Twenty-one patients were followed up after 3 months with a repeat lipid profile. Results: Mean total cholesterol and mean LDL levels were significantly higher in SH compared to controls, but there was no statistically significant difference in the mean HDL, VLDL, and triglyceride levels. There was a significant reduction in mean T. cholesterol, mean LDL, mean VLDL, and mean triglyceride levels after treatment with thyroxine, while there was no significant difference among the mean HDL levels. Conclusion: Dyslipidemia is more common in SH compared to controls. There is a TSH dependent increase in cholesterol, LDL, VLDL, and triglyceride levels. Achieving euthyroid status with thyroxine has a favourable effect on lipid profile.

  7. [Thyroxine treatment in acute renal failure (author's transl)]. (United States)

    Straub, E


    8 patients suffering from acute renal failure (shock kidney) with anuria extending over 3 to 5 days, were treated with L-thyroxine for 5 to 9 days (5-6 mug per kg body weight per day orally). Diuresis was restored within 34 to 46 hrs. Plasma levels of urea and creatinine decreased earlier and much more rapidly to normal than was to be expected from the natural history of the disease, indicating the prompt and extensive increase of glomerular filtration rate. Polyuria seemed less pronounced and also shortened as compared with the ordinary course of that form of sudden renal insufficiency. Obviously, the well-known diuretic response in the normal individual to high doses of thyroid hormones in not a factor in the induction of diuresis in acute renal failure. The tendency with L-thyroxine treatment to dilate the preglomerular arterial vessel is considered a consequence of the stimulation of sodium reabsorption in the upper nephron. High values of RPF and GFR, regularly observed in hyperthyroidism or after L-thyroxine administration, do not depend on any augmentation of cardiac output or on arterial hypertension, since such symptoms were missed in our patients and, in our view, such an interpretation is excluded by the very existence of the so-called autoregulation of the kidney which leaves RPF (and therefore GFR) independent of systemic blood pressure. The same intrarenal feed-back mechanism, normally adapting the glomerular blood supply to the resorptive capacity of the proximal-tubular epithelium (mediation via the juxta-glomerular apparatus), is responsible for the GFR- and RPF-raising effect of exogenous L-thyroxine in the intact kidney as well as in acute renal failure: both sodium reabsorption and sodium filtration are accelerated.--The special conditions under which L-thyroxine interferes with the pathogenetic process of acute renal failure, the latter being characterised by the critical insufficiency of tubular sodium reabsorption and therefore by

  8. D-propranolol and DL-propranolol both decrease conversion of L-thyroxine to L-triiodothyronine.


    Heyma, P; Larkins, R G; Higginbotham, L; Ng, K. W.


    The effects of propranolol (DL-propranolol) and D-propranolol on thyroid hormone metabolism were studied in six euthyroid volunteers receiving L-thyroxine (T4) and six hypothyroid patients receiving T4 replacement. D-propranolol as well as propranolol decreased L-triiodothyronine (T3) concentrations and the ratio of T3 to T4 in the euthyroid subjects, and D-propranolol decreased these variables in the subjects with hypothyroidism (propranolol was not given to this group). It is concluded from...

  9. Pyrroloquinoline quinone ameliorates l-thyroxine-induced hyperthyroidism and associated problems in rats. (United States)

    Kumar, Narendra; Kar, Anand; Panda, Sunanda


    Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant. In this study, we have evaluated its hitherto unknown role in l-thyroxin (L-T4 )-induced hyperthyroidism considering laboratory rat as a model. Alterations in the serum concentration of thyroxin (T4 ) and triiodothyronine (T3 ); lipid peroxidation (LPO) of liver, kidney, heart, muscles and brain; in the endogenous antioxidants such as superoxide dismutase, catalase and glutathione and in serum total cholesterol, high-density lipoprotien, triglycerides, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and urea were evaluated. Administration of l-T4 (500-µg kg(-1) body weight) enhanced not only the serum T3 and T4 levels but also the tissue LPO, serum SGOT, SGPT and urea with a parallel decrease in the levels of antioxidants and serum lipids. However, on simultaneous administration of PQQ (5 mg kg(-1) for 6 days), all these adverse effects were ameliorated, indicating the potential of PQQ in the amelioration of hyperthyroidism and associated problems. Possibly, the curative effects were mediated through inhibition of oxidative stress. We suggest that PQQ may be considered for therapeutic use for hyperthyroidism after dose standardization.

  10. Thyroxine reversibly inhibits the uncoupling action of protonophores on energy production in rat thymus lymphocytes. (United States)

    Palamarchuk, L A; Mansurova, S E; Starkov, A A


    Earlier we reported that some thyroid and steroid hormones and also 6-ketocholestanol used in micromolar concentrations modulated the effects of protonophoric uncouplers on isolated mitochondria (Starkov et al. (1997) Biochim. Biophys. Acta, 1318, 173-183). In the present study we investigated the effects of a thyroid hormone, thyroxine, on energy coupling of intact rat thymus lymphocytes and mitochondria isolated from these cells. The resting (oligomycin-inhibited) respiration of the isolated intact lymphocytes was stimulated by the addition of protonophoric uncouplers 2,4-DNP, FCCP, or SF6847. Subsequent addition of micromolar concentrations of thyroxin decreased the rate of uncoupler-stimulated respiration and partially reversed uncoupler-induced decrease of membrane potential (DeltaPsi). In experiments with mitochondria isolated from thymus lymphocytes the re-coupling effect of thyroxine was not observed. In this case thyroxine did not influence mitochondrial respiration stimulated with 2,4-DNP, but did potentiate the stimulation of respiration and DeltaPsi decrease induced with another uncoupler, SF6847. The data are discussed in terms of a hypothesis that aromatic uncouplers are transported into the cell by the thyroxine carrier of the plasma membrane.

  11. Thyroxine Induced Resorption of Xenopus Laevis Tail Tissue in Vitro. (United States)

    Scadding, Steven R.


    A simple method of studying thyroxine-induced resorption of tadpole tails in vitro is described. This procedure demonstrates that resorption is dependent on thyroxine and requires protein synthesis. It introduces students to the use of tissue culture methods. (Author)

  12. Effects of thyroxin therapy on different analytes related to obesity and inflammation in dogs with hypothyroidism. (United States)

    Tvarijonaviciute, A; Jaillardon, L; Cerón, J J; Siliart, B


    Hypothyroidism in dogs is accompanied by changes in intermediary metabolism including alterations in bodyweight (BW), insulin resistance, and lipid profile. In this study, changes in selected adipokines (adiponectin, leptin), butyrylcholinesterase (BChE), and acute phase proteins, including C-reactive protein, haptoglobin (Hp) and serum amyloid A (SAA), were studied in dogs with hypothyroidism under thyroxin therapy. Blood samples were collected when hypothyroidism was diagnosed (before treatment) and after treatment with thyroxin. Twenty-eight of 39 dogs exhibited a good therapeutic response (group A), whereas the remainder were considered to have been insufficiently treated (group B). Following treatment, group A dogs demonstrated a statistically significant decrease in canine thyroid stimulating hormone (c-TSH) (Pdogs showed no statistically significant changes in c-TSH, but had a significant increase in fT4 (Pdogs. The mean increase in Hp values and decrease in SAA for some of the dogs after treatment warrants further investigation.

  13. Developmental Triclosan Exposure Decreases Maternal,Fetal, and Early Neonatal Thyroxine: Dynamic and Kinetic Data Support for a Mode-of-Action (United States)

    This work tests the mode-of-action (MOA) hypothesis that perinatal triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via activation of pregnane X and/or constitutive androstane receptors (PXR, CAR), resulting in up-regulation of hepatic catabolism and e...

  14. Free serum thyroxine. Analysis of its clinical value through ''ROC'' curves

    Energy Technology Data Exchange (ETDEWEB)

    Degrossi, O.J.; Altschuler, N.; de Cabrejas, M.L. (Comision Nacional de Energia Nuclear Atomica, Buenos Aires (Argentina). Dept. Aplicaciones Biologicas); Pinkas, M.; Garcia del Rio, H. (Hospital Aleman, Buenos Aires (Argentina). Servicio de Medicina Nuclear)


    The use of radiommunoassay (RIA) tehcniques has increased the diagnosis of thyroid functional alterations. A solid phase RIA method for free thyroxine (FT4) measurement was tested. Serum FT4, Total T4, T3 and TSH were determined by radioimmunoassay in 179 subjects. One hundred twenty two patients were normal (8 to 75 years old); FT4 was 1.42 +- 0.03 ng/100 ml (avg. value and std. error). In 27 cases of thyrotoxicosis the values were 4.66 +- 0.48 ng/100 ml and in 15 cases of hypothyroidism 0.50 +- 0.06 ng/100 ml (statistics probability <0,01). Four euthyroid patients under estrogen treatment, 9 hypothyroid patients under l-thyroxine treatment, one hyperthyroid patient under antithyroid drugs and one hyperthyroid patient under estrogen treatment, were studied. Total T4 and T3 values were in agreement with the variations of the serum protein transport capacity, and for that reason did not show the real thyroid function state. Clinical decision making analysis (with Receiver Operating Characteristic (ROC) curves) indicate that FT4 is the best choice for hyperthyroidism diagnosis and T4 for hypothyroidism. Cost/benefit analysis indicates also that FT4 has the best ratio.

  15. Thyroxine modifies the effects of growth hormone in Ames dwarf mice (United States)

    Do, Andrew; Menon, Vinal; Zhi, Xu; Gesing, Adam; Wiesenborn, Denise S.; Spong, Adam; Sun, Liou; Bartke, Andrzej; Masternak, Michal M.


    Ames dwarf (df/df) mice lack growth hormone (GH), thyroid stimulating hormone and prolactin. Treatment of juvenile df/df mice with GH alone stimulates somatic growth, reduces insulin sensitivity and shortens lifespan. Early‐life treatment with thyroxine (T4) alone produces modest growth stimulation but does not affect longevity. In this study, we examined the effects of treatment of juvenile Ames dwarf mice with a combination of GH + T4 and compared them to the effects of GH alone. Treatment of female and male dwarfs with GH + T4 between the ages of 2 and 8 weeks rescued somatic growth yet did not reduce lifespan to match normal controls, thus contrasting with the previously reported effects of GH alone. While the male dwarf GH + T4 treatment group had no significant effect on lifespan, the female dwarfs undergoing treatment showed a decrease in maximal longevity. Expression of genes related to GH and insulin signaling in the skeletal muscle and white adipose tissue (WAT) of female dwarfs was differentially affected by treatment with GH + T4 vs. GH alone. Differences in the effects of GH + T4 vs. GH alone on insulin target tissues may contribute to the differential effects of these treatments on longevity. PMID:25935838

  16. Measurement of free thyroxine and free triiodothyronine concentrations by DPC RIA kits

    Energy Technology Data Exchange (ETDEWEB)

    Kasagi, Kanji; Kousaka, Tadako; Hatabu, Hiroto; Tokuda, Yasutaka; Iida, Yasuhiro; Konishi, Junji


    'DPC RIA' kits for measuring free triiodothyronine (T3) and free thyroxine (T4) were fundamentally and clinically studied. Standard curves for incubation temperature and time were favorable. The present kits yielded satisfactory precision and reproducibility. The upper and lower limits of the normal range for T4 were 0.88 ng/dl and 2.08 ng/dl, respectively. The serum concentration of T4 was 3.91 ng/dl or more for hyperthyroidism and 0.57 ng/dl or less for hypothyroidism, allowing discrimination between the two diseases. For T3, the upper and lower limits of the normal range were 1.45 ng/dl and 3.45 ng/dl, respectively. In pregnant women and patients with decreased or increased levels of thyroxine binding globulin (TBG), the serum T3 concentration lay within the normal range. Low free T4 and T3 levels were found in 22 % and 67 %, respectively, of patients with serious non-thyroidal illness (NTI). There was a good correlation between the present kits and the other commercially available kits. Measurements of free T3 and T4 obtained by ''Amerlex RIA'' kits tended to be lower than those by the present kits in pregnant women and NTI patients with hypoalbuminemia. In view of the simplified procedure, satisfactory precision and reproducibility, and the lack of influences of serum albumin and TBG, the present kits have a potential in routine use. (Namekawa, K.).

  17. Influences of hypertonic and hypovolemic treatments on vasopressin response in propylthiouracil (PTU) induced hypothyroid rat and effect on supplementation with L-thyroxine. (United States)

    Aydin, Leyla; Mogulkoc, R; Baltaci, A K


    This study was performed to investigate the effects of L-thyroxine treatment on plasma vasopressin (AVP) levels in rats with hypothyroidism induced by propylthiouracil (PTU). Animals were separated into three groups each having 6 rats: control, PTU, PTU+L-thyroxine groups. Then, the groups were further divided into 3 sub-groups including 6 rats (a; basal, b; hypertonic stimulated and c; hypovolemic stimulated). At the end of the experiments all rats were decapitated in order to obtain plasma samples for analysis in terms of Hct, osmolality, TT 3 , TT 4 and vasopressin. Haematocrit (Hct) levels were the highest in hypovolemic stimulated sub-group (P PTU group and the highest in the L-thyroxine treated group (P PTU group (P PTU-induced hypothyroidism. However, L-thyroxine treatment following hypothyroidism prevents this reduction.

  18. Multicompartmental model for iodide, thyroxine, and triiodothyronine metabolism in normal and spontaneously hyperthyroid cats

    Energy Technology Data Exchange (ETDEWEB)

    Hays, M.T.; Broome, M.R.; Turrel, J.M.


    A comprehensive multicompartmental kinetic model was developed to account for the distribution and metabolism of simultaneously injected radioactive iodide (iodide*), T3 (T3*), and T4 (T4*) in six normal and seven spontaneously hyperthyroid cats. Data from plasma samples (analyzed by HPLC), urine, feces, and thyroid accumulation were incorporated into the model. The submodels for iodide*, T3*, and T4* all included both a fast and a slow exchange compartment connecting with the plasma compartment. The best-fit iodide* model also included a delay compartment, presumed to be pooling of gastrosalivary secretions. This delay was 62% longer in the hyperthyroid cats than in the euthyroid cats. Unexpectedly, all of the exchange parameters for both T4 and T3 were significantly slowed in hyperthyroidism, possibly because the hyperthyroid cats were older. None of the plasma equivalent volumes of the exchange compartments of iodide*, T3*, or T4* was significantly different in the hyperthyroid cats, although the plasma equivalent volume of the fast T4 exchange compartments were reduced. Secretion of recycled T4* from the thyroid into the plasma T4* compartment was essential to model fit, but its quantity could not be uniquely identified in the absence of multiple thyroid data points. Thyroid secretion of T3* was not detectable. Comparing the fast and slow compartments, there was a shift of T4* deiodination into the fast exchange compartment in hyperthyroidism. Total body mean residence times (MRTs) of iodide* and T3* were not affected by hyperthyroidism, but mean T4* MRT was decreased 23%. Total fractional T4 to T3 conversion was unchanged in hyperthyroidism, although the amount of T3 produced by this route was increased nearly 5-fold because of higher concentrations of donor stable T4.

  19. Effects of prolonged fasting on plasma cortisol and TH in postweaned northern elephant seal pups (United States)

    Ortiz, R. M.; Wade, C. E.; Ortiz, C. L.


    Northern elephant seal (Mirounga angustirostris) pups rely on the oxidation of fat stores as their primary source of energy during their 8- to 12-wk postweaning fast; however, potential endocrine mechanisms involved with this increased fat metabolism have yet to be examined. Therefore, 15 pups were serially blood sampled in the field during the first 7 wk of their postweaning fast to examine the changes in plasma concentrations of cortisol and thyroid hormones (TH), which are involved in fat metabolism in other mammals. Cortisol increased, indicating that it contributed to an increase in lipolysis. Increased total triiodothyronine (tT(3)) and thyroxine (tT(4)) may not reflect increased thyroid gland activity, but rather alterations in hormone metabolism. tT(3)-to-tT(4) ratio decreased, suggesting a decrease in thyroxine (T(4)) deiodination, whereas the negative correlation between total proteins and free T(4) suggests that the increase in free hormone is attributed to a decrease in binding globulins. Changes in TH are most similar to those observed during hibernation than starvation in mammals, suggesting that the metabolic adaptations to natural fasting are more similar to hibernation despite the fact these animals remain active throughout the fasting period.

  20. Overview of the Lockheed Martin Compact Fusion Reactor (CFR) T4B Experiment (United States)

    McGuire, Thomas


    The Lockheed Martin Compact Fusion Reactor (CFR) Program endeavors to quickly develop a compact fusion power plant with favorable commercial economics and military utility. The CFR uses a diamagnetic, high beta, magnetically encapsulated, linear ring cusp plasma confinement scheme. The goal of the T4B experiment is to demonstrate a suitable plasma target for heating experiments and to characterize the behavior of plasma sources in the CFR configuration. The design of the T4B experiment will be presented, including discussion of predicted behavior, plasma sources, heating mechanisms, diagnostics suite and relevant numerical modeling. ©2016 Lockheed Martin Corporation. All Rights Reserved.

  1. Acute mania after thyroxin supplementation in hypothyroid state

    Directory of Open Access Journals (Sweden)

    Rohit Verma


    Full Text Available The current literature variedly ascribes depressive and manic symptoms to hypo- and hyperthyroid state, respectively, reporting mania in hypothyroidism as an unusual entity. More unusual is precipitation of manic state in hypothyroid subjects after thyroxine supplementation for which studies report otherwise treating manic symptoms in hypothyroid state with thyroxine. We report a case of a patient whose acute mania appears to have been precipitated by thyroxine supplementation in hypothyroidism state. This case underscores the importance of thyroid screening in patients with mood and psychotic disorders, as well as the potency of thyroxine in producing manic symptoms.

  2. Thyroxine differentially modulates the peripheral clock: lessons from the human hair follicle.

    Directory of Open Access Journals (Sweden)

    Jonathan A Hardman

    Full Text Available The human hair follicle (HF exhibits peripheral clock activity, with knock-down of clock genes (BMAL1 and PER1 prolonging active hair growth (anagen and increasing pigmentation. Similarly, thyroid hormones prolong anagen and stimulate pigmentation in cultured human HFs. In addition they are recognized as key regulators of the central clock that controls circadian rhythmicity. Therefore, we asked whether thyroxine (T4 also influences peripheral clock activity in the human HF. Over 24 hours we found a significant reduction in protein levels of BMAL1 and PER1, with their transcript levels also decreasing significantly. Furthermore, while all clock genes maintained their rhythmicity in both the control and T4 treated HFs, there was a significant reduction in the amplitude of BMAL1 and PER1 in T4 (100 nM treated HFs. Accompanying this, cell-cycle progression marker Cyclin D1 was also assessed appearing to show an induced circadian rhythmicity by T4 however, this was not significant. Contrary to short term cultures, after 6 days, transcript and/or protein levels of all core clock genes (BMAL1, PER1, clock, CRY1, CRY2 were up-regulated in T4 treated HFs. BMAL1 and PER1 mRNA was also up-regulated in the HF bulge, the location of HF epithelial stem cells. Together this provides the first direct evidence that T4 modulates the expression of the peripheral molecular clock. Thus, patients with thyroid dysfunction may also show a disordered peripheral clock, which raises the possibility that short term, pulsatile treatment with T4 might permit one to modulate circadian activity in peripheral tissues as a target to treat clock-related disease.

  3. The metabolic consequences of thyroxine replacement in adult hypopituitary patients

    DEFF Research Database (Denmark)

    Filipsson Nyström, Helena; Feldt-Rasmussen, Ulla; Kourides, Ione;


    The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n = 1595) with and without CH from KIMS (Pfizer International Metabolic Database...

  4. The relationship between serum TSH and free T4 in older people. (United States)

    Clark, Penny M; Holder, Roger L; Haque, Sayeed M; Hobbs, F D Richard; Roberts, Lesley M; Franklyn, Jayne A


    The frequency distribution of serum thyroid stimulating hormone (TSH) shows a skewed pattern that may change with age. The set point of the hypothalamic-pituitary-thyroid axis for an individual is thought to be genetically determined and has been described as a log-linear relationship of serum TSH to free thyroxine (T4); however, the validity of this hypothesis has yet to be established in older people. The aim of the study was to describe the relationship between serum TSH and free T4 in older people and define factors influencing this relationship. We conducted a cross-sectional, observational study of thyroid function in a community population of older subjects over 65 years of age. The relationship between serum TSH and free T4 was not linear as previously described, but is best described as a fourth-order polynomial. Both gender and smoking status affected the relationship. This suggests that more complex modelling is required when investigating the hypothalamic-pituitary-thyroid axis.

  5. Contribution of maternal thyroxine to fetal thyroxine pools in normal rats near term

    Energy Technology Data Exchange (ETDEWEB)

    Morreale de Escobar, G.; Calvo, R.; Obregon, M.J.; Escobar Del Rey, F. (Instituto de Investigaciones Biomedicas, Madrid (Spain))


    Normal dams were equilibrated isotopically with ({sup 125}I)T4 infused from 11 to 21 days of gestation, at which time maternal and fetal extrathyroidal tissues were obtained to determine their ({sup 125}I)T4 and T4 contents. The specific activity of the ({sup 125}I)T4 in the fetal tissues was lower than in maternal T4 pools. The extent of this change allows evaluation of the net contribution of maternal T4 to the fetal extrathyroidal T4 pools. At 21 days of gestation, near term, this represents 17.5 +/- 0.9% of the T4 in fetal tissues, a value considerably higher than previously calculated. The methodological approach was validated in dams given a goitrogen to block fetal thyroid function. The specific activities of the ({sup 125}I)T4 in maternal and fetal T4 pools were then similar, confirming that in cases of fetal thyroid impairment the T4 in fetal tissues is determined by the maternal contribution. Thus, previous statements that in normal conditions fetal thyroid economy near term is totally independent of maternal thyroid status ought to be reconsidered.

  6. Genetic Exclusion in Bacteriophage T4. (United States)


    ofI resource acquisition, but their genetic determinants are physicall .- linked and possibly co-regiulated or, the same sect ion of DNA. Thec o-eria...7473-7481. Garen, A. (1968). Sense and Nonsense in the Genetic Lode. Science 160:149-159. ( elIer, A. I . and A. rich (1980). A LGA ferarinatio...Mutants Deficient in rni Exclusion. Science 158:1588-1589. 11saio, C. L. and L. W. Black (1977). DNA Plackaging- and the Pathway of Bacteriophage T4

  7. Inner ring deiodination of thyroxine and 3,5,3'-triiodothyronine by human fetal membranes

    Energy Technology Data Exchange (ETDEWEB)

    Roti, E.; Fang, S.L.; Green, K.; Braverman, L.E.; Emerson, C.H.


    Indirect evidence, based on injection of thyroxine (T4) into the amniotic cavity of humans, and maternal thyroidectomy in the rat, suggests that fetal membranes might be capable of converting T4 to 3,3',5'-triiodothyronine (rT3) by virtue of inner ring iodothyronine deiodinase activity. The present study was undertaken to provide direct evidence that human fetal membranes contain inner ring iodothyronine deiodinase activity directed toward T4 and 3,5,3'-triiodothyronine (T3). Homogenates of human fetal membranes were incubated with 125I-labeled T4, rT3, and T3, and with stable T4. Conversion of 125(I)-T4 to 125(I)-rT3 was noted in chorion and amnion. 125I-T3 was converted to 125(I)-3,3'-diiodothyronine (T2) in chorion and amnion. 125(I)-rT3 was stable in fetal membranes under the incubation conditions employed. Time-, temperature-, pH-, and protein content-dependent conversion of stable T4 to rT3 was found in fetal membranes. Iodothyronine metabolism did not occur in the absence of dithiothreitol. These studies indicate that human fetal membranes contain an inner ring deiodinase enzyme. Because of its intimate contact with the amniotic cavity, this enzyme may generate a portion of the rT3 found in amniotic fluid.

  8. Diagnostic Evaluation of Effective Thyroxine Ratio

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myung Chul; Choi, Sang Jae; Ro, Heung Kyu; Lee, Hong Kyu; Koh, Chang Soon; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    The purpose of the present study is to evaluate the diagnostic value of the ETR test as compared to other thyroid function tests in normal persons, patients with thyroid disorders and patients with alterations of thyroxine-binding proteins. The ETR values were obtained from 35 cases as normal control, 63 hyperthyroid patients, 56 euthyroid patients, 23 hypothyroid patients, 10 pregnant women, 5 women taking oral contraceptive medication, 8 liver cirrhosis patients and 4 nephrotic syndrome patients. The results obtained were as follows. 1) The mean value of ETR obtained from the normal controls was 0.99+-0.06. 2) The mean ETR values of various thyroid states were 1.25+-0.16 in hyperthyroidism, 0.99+-0.08 in euthyroidism and 0.82+-0.05 in hypothyroidism and significant difference was found between these groups. 3) Seven out of 63 hyperthyroid patients (11.1%) and 2 out of 23 hypothyroid patients (8.7%) had ETR values within normal range and among the 56 euthyroid patients 6 (10.7%) had ETR values outside normal range, so the diagnostic compatibility of ETR was 89.4% in thyroid diseases. 4) Even though the ETR value was well correlated with {sup 131}I-thyroid uptake rate, serum T{sub 3} resin uptake rate and serum T{sub 4}, a high positive correlation was found (r=0.79) between ETR and T{sub 7}. 5) The mean ETR values from patients with alteration in TBG binding capacity were 0.99+-0.05 in pregnant women, 0.98+-0.04 in women with oral contraceptive medication, 1.04+-0.09 in liver cirrhosis patients and 0.94+-0.02 in nephrotic syndrome patients and most of them (85.2%) had ETR values within normal range. Our results, therefore, suggests that the ETR estimation does offer the simplest and most reliable single procedure for the screening and diagnosis of various thyroid diseases as a indirect indicator of serum-free thyroxine concentration without essential influence of changes in the thyroxine-binding proteins in serum.

  9. Individually-tailored thyroxine requirement in the same patients before and after thyroidectomy: a longitudinal study. (United States)

    Del Duca, S C; Santaguida, M G; Brusca, N; Gatto, I; Cellini, M; Gargano, L; Verga Falzacappa, C; Frattaroli, F M; Virili, C; Centanni, M


    Thyroxine (T4) requirement after total thyroidectomy for differentiated thyroid carcinoma (DTC) is a debated issue. As most of the studies in the area have been retrospective and/or performed with heterogeneous therapeutic approaches, we designed our study to determine T4 requirement in the same patients and treatment settings, before and after total thyroidectomy. This was a longitudinal study including 23 goitrous patients treated with T4 in an individually tailored fashion. All patients exhibited a stable TSH (median TSH = 0.28 mU/l) at a stable T4 dose for at least 1 year before surgery (median T4 dose = 1.50 μg/kg per day). The patients underwent total thyroidectomy based on cancer suspicion or compressive symptoms. Eventually diagnosed as having DTC (pT1b-pT2N0) and following surgical and radiometabolic treatment, they were treated with the same pre-surgical doses of T4. Three months after surgery,using the same pre-surgical dose, median TSH increased up to 5.38 mU/l (P<0.0001) and so the T4 dose had to be increased (median T4 dose = 1.95 μg/kg per day; +30%; P < 0.0001). Once divided by patients' age, we observed that, after thyroidectomy and maintaining the same pre-surgical dose, serum TSH significantly increased both in younger and in older patients (median TSH = 4.57 and 6.11 mU/l respectively). Serum TSH was restored to the pre-surgical level by increasing the dose up to 1.95 and 1.77 μg/kg per day (+25 and +21%) respectively. Following the same treatment regimen, a thyroidectomized patient requires one-third higher therapeutic T4 dose than before surgery. Despite this increase, the dose of T4 needed in our patients remains significantly lower than that previously described in athyreotic patients. © 2015 European Society of Endocrinology.

  10. Thyroxine clearance in rats within the first month after the single whole-body {gamma} - irradiation at a dose of 10Gy

    Energy Technology Data Exchange (ETDEWEB)

    Pryadko, Kirill A. [Institute of Radiobiology, National Academy of Sciences, Minsk (Belarus)


    The effects of acute whole-body {gamma} -irradiation at a dose of 10 Gy on thyroxine (T{sub 4}) plasma clearance rate (PCR) and thyroidal and blood T4 concentration ([T{sub 4}]) were examined within one month after exposure. The PCR values were measured using the bolus injection, single-compartmental approach. To eliminate the influence of radiation-induced anorexia animals were fasting for two days before the pharmacokinetic experiments. Hormone concentrations in blood and in thyroid tissue were measured by RIA. Throughout the observation period, PCR was elevated in irradiated rats with maximum at day 4 after exposure (0.56{+-}0.04 vs. 0.36{+-}0.03 ml/h100 gbw, P<0.001). [T{sub 4}] in blood was not significantly different from that in control animals. Thyroidal [T{sub 4}] was significantly decreased in irradiated animals 4 days after exposure (151.8{+-}21.7 vs. 258.8{+-}29.9 pmol/mg protein, P<0.01) and gradually increased after day 9. 10 Gy {gamma} -irradiation causes the intensification of T{sub 4} metabolism without the pronounced changes in concentration. Presumably, at early terms the rising local demand in O{sub 4} can not be compensated with the existing level of production. Alterations in the intensity of T{sub 4} metabolism are evident at least one month after exposure but they may not be detected without taking into account kinetic data.

  11. Intracellular Conversion of Thyroxine to Triidothyronine Is Required for the Optimal Thermogenic Function of Brown Adipose Tissue



    The effect of thyroxine (T4) and triiodothyronine (T3) on the expression of uncoupling protein (UCP) in rat brown adipose tissue (BAT) has been examined. Thyroidectomized rats have a threefold reduction in basal UCP levels. When exposed to cold, they become hypothermic and show a fivefold lower response of UCP than euthyroid controls. T3 augments the basal levels and the response of UCP and its mRNA to cold in a dose-dependent manner. However, to normalize the response of UCP, T3 has to be gi...

  12. Effect of thyroxine treatment on carnitine levels in mice. (United States)

    Cederblad, G; Engström, G


    The effect in mice of 8 subcutaneous injections of 20 microgram of L-thyroxine at 12 hr-intervals on the carnitine concentration in the heart and skeletal muscle tissue was studied. In skeletal muscle tissue, the thyroxine treatment resulted in a depressed carnitine concentration. The mean values were 1.59 +/- 0.034 (S.E.M.) and 2.03 +/- 0.045 mumol/g noncollagen protein and 1.11 +/- 0.035 and 1.45 +/- 0.037 mumol/g dry weight for the thyroxine treated and the control animals, respectively. Thyroxine produced myocardial hypertrophy. The thyroxine treated animals had lower cardiac values when dry weight was used as reference base 4.17 +/- 0.10 mumol/g dry weight than the control group, 4.69 +/- 0.18 mumol/g dry weight. No statistically significant difference was found between the two groups when the cardiac carnitine concentration was expressed per g noncollagen protein or as carnitine in the entire hearts. Thus, thyroxine has been showed to influence the metabolism of carnitine in mice.

  13. TSH-Based Protocol, Tablet Instability, and Absorption Effects on L-T4 Bioequivalence (United States)

    DiStefano, Joseph J.


    Background FDA Guidance for pharmacokinetic (PK) testing of levothyroxine (L-T4) for interbrand bioequivalence has evolved recently. Concerns remain about efficacy and safety of the current protocol, based on PK analysis following supraphysiological L-T4 dosing in euthyroid volunteers, and recent recalls due to intrabrand manufacturing problems also suggest need for further refinement. We examine these interrelated issues quantitatively, using simulated what-if scenarios testing efficacy of a TSH-based protocol and tablet stability and absorption, to enhance precision of L-T4 bioequivalence methods. Methods We use an updated simulation model of human thyroid hormone regulation quantified and validated from data that span a wide range of normal and abnormal thyroid system function. Bioequivalence: We explored a TSH-based protocol, using normal replacement dosing in simulated thyroidectomized patients, switching brands after 8 weeks of full replacement dosing. We simulated effects of tablet potency differences and intestinal absorption differences on predicted plasma TSH, T4, and triiodothyronine (T3) dynamics. Stability: We simulated effects of potency decay and lot-by-lot differences in realistic scenarios, using actual tablet potency data spanning 2 years, comparing the recently reduced 95–105% FDA-approved potency range with the original 90–110% range. Results A simulated decrease as small as 10–15% in L-T4 or its absorption generated TSH concentrations outside the bioequivalence target range (0.5–2.5 mU/L TSH), whereas T3 and T4 plasma levels were maintained normal. For a 25% reduction, steady-state TSH changed 300% (from 1.5 to 6 mU/L) compared with <25% for both T4 and T3 (both within their reference ranges). Stability: TSH, T4, and T3 remained within normal ranges for most potency decay scenarios, but tablets of the same dose strength and brand were not bioequivalent between lots and between fresh and near-expired tablets. Conclusions A

  14. T-4G Simulator and T-4 Ground Training Devices in USAF Undergraduate Pilot Training. (United States)

    Woodruff, Robert R.; Smith, James F.

    The objective of the project was to investigate the utility of using an A/F37A-T4G T-37 flight simulator within the context of Air Force undergraduate pilot training. Twenty-one subjects, selected from three undergraduate pilot training classes, were given contact flight training in a TP4G/EPT simulator before going to T-37 aircraft for further…

  15. Thyroxine inner ring monodeiodinating activity in fetal tissues of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Huang, T.S.; Chopra, I.J.; Boado, R.; Soloman, D.H.; Chua Teco, G.N.


    We studied thyroxine (T4) inner ring monodeiodinating activity (5-MA) in various tissues of fetal, maternal, and adult male rats. Tissue homogenates were incubated with 0.26 microM T4 in 0.1 M phosphate buffer (pH 7.4) containing 10 mM EDTA and 400 mM dithiothreitol (final volume 0.7 ml) for 10 min at 37 degrees C; the 3,3',5'-triiodothyronine (rT3) generated was measured by radioimmunoassay of ethanol extracts of incubation mixture and the result was corrected for rT3 degradation during incubation. Compared to maternal tissues, T4 to rT3 5-MA in the 14-day-old fetus was increased about 70 times in skeletal muscle (mean +/- SEM, velocity, 5.4 +/- 0.9 versus 0.08 +/- 0.01, pmol rT3/h/mg protein); approximately 8 times in intestine (0.72 +/- 0.17 versus 0.09 +/- 0.03);and approximately 4 times in cerebral cortex (19 +/- 0.5 versus 4.5 +/- 0.9), while it was similar in skin (3.2 +/- 0.48 versus 2.6 +/- 0.52). Hepatic T4 5-MA approximated 1.1 +/- 0.63 in the 14-day-old fetus; it could not be measured reliably in maternal or 19-day fetal tissue because of extensive (greater than 90%) degradation of rT3 during incubation. Relative to mother, T4 5-MA in 19-day fetal tissues was increased approximately 30-fold intestine, approximately 20-fold in skeletal muscle, and approximately 6-fold in cerebral cortex while it was similar in skin. The T4 5-MA in maternal rat tissues did not differ significantly from corresponding values in adult male rat, except skin, where it was lower in the mother rat (2.6 +/- 0.52 versus 4.6 +/- 0.61, p less than 0.05). In summary, relative to adult tissues T4 5-MA is exceedingly active in several fetal tissues, most notably in skeletal muscle followed by intestine and cerebral cortex.

  16. [Olpadronate prevents cortical and trabecular bone loss induced by supraphysiological dosis of thyroxine in ovariectomized rats]. (United States)

    Zeni, S N; Gómez Acotto, C; Di Gregorio, S


    The aim of the present report was to clarify the effect of excess T4 on axial and peripheral bone mineral density (BMD) in estrogen-depleted rats. The protective effect of olpadronate (Olpa) on axial and peripheral bone mass in thyroxine-treated rats was also investigated. Female Sprague-Dawley rats were used: SHAM, OVX + Vh, OVX + Olpa (0.3 mg/kg/week), OVX + T4 (250 micrograms/kg/day) and OVX + T4 + Olpa rats. OVX + Vh group presented a BMD lower than SHAM in the tibia (p < 0.01) but not in femur or lumbar spine; the middle tibia BMD did not change but it was lower at the distal (pns.) and proximal levels (p < 0.003) in OVX + Vh. OVX + T4 rats presented a BMD significantly lower than OVX + Vh rats in total tibia (p < 0.02), femur (p < 0.006) and lumbar spine (p < 0.006). Moreover the BMD was lower in all studied areas of the tibia, but it was statistically significant only at the middle level (p < 0.004). OVX + Olpa rats had a BMD higher than OVX + Vh rats in femur (p < 0.002), lumbar spine (p < 0.0001), total (p < 0.001) and proximal tibia (p < 0.001). Surprisingly, total and proximal tibia BMD values in OVX + Olpa rats presented a BMD significantly higher than OVX + T4 rats in femur (p < 0.001), lumbar spine (p < 0.001), tibia (p < 0.001) and proximal tibia (p < 0.0001). It is important to point out that OVX + T4 + Olpa BMD was significantly higher than in SHAM rats at the lumbar spine, total and proximal tibia (p < 0.01). The present study suggests that although supraphysiological thyroid hormone affected both cortical and trabecular bone, under estrogen-depleted conditions, the cortical bone appears to be more sensitive than the trabecular bone to T4 treatment. We also found that Olpa could prevent the peripheral and axial bone loss induced by thyroid hormone excess.

  17. Seasonal variations in TSH serum levels in athyreotic patients under L-thyroxine replacement monotherapy. (United States)

    Gullo, Damiano; Latina, Adele; Frasca, Francesco; Squatrito, Sebastiano; Belfiore, Antonino; Vigneri, Riccardo


    Whether serum TSH undergoes seasonal fluctuations in euthyroid and hypothyroid residents of temperate climates is controversial. Monthly TSH and thyroid hormone levels were cross-sectionally analysed in a large cohort of euthyroid subjects (n=11 806) and L-thyroxine (L-T4)-treated athyreotic patients (n=3 934). Moreover, in a small group (n=119) of athyreotic patients treated with an unchanged dosage of L-T4 monotherapy, hormones were measured both in the coldest and in the hottest seasons of the same year (longitudinal study). No seasonal hormone change was observed in the euthyroid subjects except for a small FT3 increase in winter (+2.9%, PL-T4-treated athyreotic patients had significantly higher serum TSH values in the cold season when the FT4 values were significantly lower. The differences were more notable in the longitudinal series (TSH, 0.80 vs. 0.20 mU/L and FT4, 16.3 vs. 17.8 pmol/L in December-March vs. June-September, respectively). In these patients also serum FT3 values significantly decreased in winter (in the longitudinal series, 3.80 in winter vs 4.07 pmol/L in summer). Regression analysis showed that in athyreotic subjects, a greater FT4 change is required to obtain a TSH change similar to that of euthyroid controls and that this effect is more pronounced in the summer. Athyreotic patients undergoing L-T4 monotherapy have abnormal seasonal variations in TSH. These changes are secondary to the FT4 and FT3 serum decreases in winter, which occur in spite of the constant treatment. The underlying mechanisms are unclear, but in some cases, these changes may be clinically relevant. © 2017 John Wiley & Sons Ltd.

  18. Effects of thyroxine and dexamethasone on rat submandibular glands

    Energy Technology Data Exchange (ETDEWEB)

    Sagulin, G.B.; Roomans, G.M. (Karolinska Institutet, Huddinge (Sweden))


    Glucocorticoids and thyroxine are known to have a marked effect on the flow rate and protein composition of rat parotid saliva in hormonally intact animals. In the present study, the effects of a one-week treatment of male rats with dexamethasone and thyroxine were studied by electron microscopy and x-ray micro-analysis, and by measurement of the flow rate and determination of the chemical composition of pilocarpine-induced submandibular saliva. Thyroxine had the most extensive effects on the submandibular gland. The acinar cells were enlarged and filled with mucus; the cellular calcium concentration was significantly increased. The flow rate of the submandibular saliva was significantly reduced compared with that in saline-injected control animals. Thyroxine caused an increase in the concentrations of protein, total calcium, and potassium in the saliva. Dexamethasone had no significant effects on gland ultrastructure or on the elemental composition of the acinar cells; flow rate was not affected, but the concentrations of protein, calcium, and potassium were significantly increased. The effects of dexamethasone and thyroxine on the flow rate and protein composition of pilocarpine-induced rat submandibular saliva differ from those reported earlier for rat parotid saliva after simultaneous stimulation with pilocarpine and isoproterenol.

  19. Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism.

    LENUS (Irish Health Repository)

    Adrees, M


    CONTEXT: Some of the cardiovascular and renal abnormalities seen in overt hypothyroidism have also been reported in subclinical hypothyroidism (SCH). Short-term L-T4 replacement in SCH improves cardiovascular risk markers and reduces carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis. The haemodynamic and renal effects of L-T4 replacement in SCH are poorly understood. OBJECTIVES: To compare cardiovascular risk factors and renal variables in women with SCH and normal women. To study the effects of L-T4 replacement in SCH subjects on these variables and on structural and functional changes in common carotid and brachial arteries. DESIGN: Fifty-six women with SCH before and after L-T4 replacement for 18 months and 56 normal women of similar age distribution were studied. Blood Pressure (BP), plasma lipids and homocysteine were measured and renal function evaluated [estimation of glomerular filtration rate (eGFR) using standard equations and measurement of serum Cystatin-C] in women with SCH before and after 18 months of l-T4, and in healthy women. CIMT and endothelial function (using brachial artery ultrasound) were studied before and after L-T4 in a subgroup of women with SCH. RESULTS: Systolic and diastolic BP, total cholesterol, triglyceride, LDL-cholesterol, lipoprotein(a) and homocysteine were greater in SCH (P < 0.05), and following L-T4 replacement decreased (P < 0.05) to levels that no longer differed from normal subjects. Estimated GFR was reduced and serum Cystatin-C increased (P < 0.05) in SCH. These variables also normalized following L-T4. Following L-T4 replacement the carotid artery baseline diameter increased by 7.1% and CIMT decreased by a mean value of 13%, while brachial artery diameter increased basally by 12.5% and following endothelium-dependent vasodilatation by 17.5% (P < 0.05). However, the increment following reactive hyperaemia did not differ before or following L-T4 replacement. CONCLUSION: Normalization of

  20. Effects of larval-juvenile treatment with perchlorate and co-treatment with thyroxine on zebrafish sex ratios (United States)

    Mukhi, S.; Torres, L.; Patino, R.


    The objective of this study was to determine the effect of larval-juvenile exposure to perchlorate, a thyroid hormone synthesis inhibitor, on the establishment of gonadal sex ratios in zebrafish. Zebrafish were exposed to untreated water or water containing perchlorate at 100 or 250 ppm for a period of 30 days starting at 3 days postfertilization (dpf). Recovery treatments consisted of a combination of perchlorate and exogenous thyroxine (T4; 10 nM). Thyroid histology was assessed at the end of the treatment period (33 dpf), and gonadal histology and sex ratios were determined in fish that were allowed an additional 10-day period of growth in untreated water. As expected, exposure to perchlorate caused changes in thyroid histology consistent with hypothyroidism and these effects were reversed by co-treatment with exogenous T4. Perchlorate did not affect fish survival but co-treatment with T4 induced higher mortality. However, relative to the corresponding perchlorate concentration, co-treatment with T4 caused increased mortality only at a perchlorate concentration of 100 ppm. Perchlorate alone or in the presence of T4 suppressed body length at 43 dpf relative to control values. Perchlorate exposure skewed the sex ratio toward female in a concentration-dependent manner, and co-treatment with T4 not only blocked the feminizing effect of perchlorate but also overcompensated by skewing the sex ratio towards male. Moreover, co-treatment with T4 advanced the onset of spermatogenesis in males. There was no clear association between sex ratios and larval survival or growth. We conclude that endogenous thyroid hormone plays a role in the establishment of gonadal sex phenotype during early development in zebrafish. ?? 2006 Elsevier Inc. All rights reserved.

  1. Pattern of thyroid function during early pregnancy in women diagnosed with subclinical hypothyroidism and treated with l-thyroxine is similar to that in euthyroid controls. (United States)

    De Geyter, Christian; Steimann, Sabine; Müller, Beat; Kränzlin, Marius E; Meier, Christian


    Subclinical hypothyroidism (SCH) is associated with a higher miscarriage rate. It is unclear how the thyroid function in SCH differs from that in euthyroidism during early pregnancy. We intended to determine the regulation of thyroid function in women with SCH receiving constant l-thyroxine (T4) replacement during early pregnancy as compared to euthyroid controls. This was a prospective cohort study with weekly serum sampling in eight women in early pregnancy with SCH and eight euthyroid women from week 5 to week 12 of pregnancy. Thyroid function was assessed before pregnancy. Women with SCH were treated with T4 (50 microg daily) and continued on an unchanged dose until week 12. The following parameters were measured weekly: thyrotropin (TSH), thyroglobulin, thyroxine, triiodothyronine, free thyroxine (FT4), free triiodothyronine (FT3), estradiol, progesterone, human chorionic gonadotropin, and prolactin. Although the pregestational levels of TSH were significantly higher among women with SCH as compared to euthyroid controls, the self-limited estrogen-induced increment of TSH during early pregnancy was similar in both groups. Although both SCH and ovarian hyperstimulation were associated with an intermediate rise in TSH, the pattern of thyroid function followed similar changes as in euthyroid controls and is unlikely to cause the higher miscarriage rate observed in SCH.


    Directory of Open Access Journals (Sweden)

    João Teodoro Pádua


    Full Text Available

    This study was designed to evaluate changes in plasma concentrations of cortisol (Cs, triiodothyronine (T3 and thyroxine (T4, as well as their circadian rhythm during peripartal period of Quarter Horse mares. Eighteen clinically healthy mares, with age between 60 and 96 months and alive weight (AW between 350 and 420 Kg were divided in three groups (n=6 according the reproductive status, that means: no pregnant (TE, Pregnant (GE and after parturition (PA.The blood samples were taken during 24 hours in intervals of two hours.There was no differences between cortisol levels regarding the reproductive status and periods of blood samples collections. This hormone showed a circadian rhythm, with accentuated oscillation in TE, but small for GE and PA. For T3 and T4 there was difference between reproductive status (P<0.05 and P<0.01, respectively, as well as for the periods (P<0.01 and P<0.05, respectively. It was possible to characterize the circadian rhythm for both hormones, verifying great oscillation for T3 in PA in the morning. It was possible to conclude that the final phase of pregnancy alter cortisol , T3 and T4 secretion standards, keeping, however, the rhythm, suggesting an organism adaptation along the peripartal period.


    KEY WORDS: Equine, reproductive status, hormones, circadian rhythm.

    O objetivo deste estudo foi verificar as alterações nas concentrações plasmáticas e o ritmo circadiano do cortisol (Cs, triiodotironina (T3 e tiroxina (T4 no periparto de éguas da raça quarto de milha. Utilizaram-se dezoito éguas clinicamente sadias, com idade entre 60 e 96 meses e peso vivo (PV entre 350 e 420 Kg, divididas em três grupos (n=6, de acordo com o estágio reprodutivo:* vazias (TE, gestantes (GE e paridas (PA. As amostras de sangue foram colhidas

  3. 外源性甲状腺素对胎儿酒精效果出生后大鼠小脑发育的改善作用%Effect of exogenous thyroxine on postnatal development of cerebellar cortex in rats with fetal alcohol exposure

    Institute of Scientific and Technical Information of China (English)

    金福; 金正勇; 丁允英; 许春花


    Objective To investigate the influence of fetal alcohol effect on the change of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) in the rat cerebellar cortex, and the effect of exogenous thyroxine on the postnatal development of cerebellar cortex in rats with f'etal alcohol effect. Methods The rats with 6 pregnant days were divided into four groups, and consisting of the alcohol group with receiving 1 475 J liquid alcohol per day, the control group with receiving 35-calories milk per day, the alcohol + T4 group with receiving 1 475 J liquid alcohol and exogenous thyroxine (5 μg/kg·d) subcutaneously, and the surrogate group with receiving normal diet. respectively. The plasma concentrations of alcohol and thyroxine were determined in maternal rats 6 hours after delivery. All pups in the alcohol, the control and the alcohol + T4 groups were fostered by surrogate mothers. and executed under anesthesia at postnatal 7, 14, 21, 28, 60, 90 days for measuring the distributions and forms of BDNF and TrkBimmunoreactive (IR) Purkinje cells with the use of immunohistochemistry. The numbers of BDNF- and TrkB-IR Purk inje cells were counted in the lobule 4/5 of cerebellum. Results A total of 18 mother rats and 144 their pups were involved in the result analysis. The maternal alcohol concentrations in the alcohol and the alcohol + thyroxine groups were significantly higher than that in the control group (P < 0.05) , and the maternal thyroxine concentration was significantly higher in the alcohol + T4 group than that in the alcohol group (P < 0.05) . A similar developmental pattern of mature BDNF- and TrkB-IR Purkinje cells were observed in the alcohol + T4 and the control groups at P14 and after that, while their immature features were seen in the alcohol group. The single-layer arrangement of these Purkinje cells in the alcohol group was not completely achieved throughout postnatal life. No significant difference in the number of BDNF-and trk

  4. Mercury exposure associated with altered plasma thyroid hormones in the declining western pond turtle (Emys marmorata) from California mountain streams (United States)

    Meyer, Erik; Eagles-Smith, Collin A.; Sparling, Donald; Blumenshine, Steve


    Mercury (Hg) is a global threat to wildlife health that can impair many physiological processes. Mercury has well-documented endocrine activity; however, little work on the effects of Hg on the thyroid hormones triiodothyronine (T3) and thyroxine (T4) in aquatic wildlife exists despite the fact that it is a sensitive endpoint of contaminant exposure. An emerging body of evidence points to the toxicological susceptibility of aquatic reptiles to Hg exposure. We examined the endocrine disrupting potential of Hg in the western pond turtle (Emys marmorata), a long-lived reptile that is in decline throughout California and the Pacific Northwest. We measured total Hg (THg) concentrations in red blood cells (RBCs) and plasma T3 and T4 of turtles from several locations in California that have been impacted by historic gold mining. Across all turtles from all sites, the geometric mean and standard error THg concentration was 0.805 ± 0.025 μg/g dry weight. Sampling region and mass were the strongest determinants of RBC THg. Relationships between RBC THg and T3 and T4 were consistent with Hg-induced disruption of T4 deiodination, a mechanism of toxicity that may cause excess T4 levels and depressed concentrations of biologically active T3.

  5. The effect of life-long thyroxine treatment and physical activity on bone mineral density in young adult women with congenital hypothyroidism

    NARCIS (Netherlands)

    M.J.E. Kempers; T. Vulsma; B.M. Wiedijk; M. de Vijlder; B.L.F. van Eck-Smit; H.J. Verberne


    Objective: Normalization of plasma thyrotropin in T-4-Supplemented patients with thyroidal congenital hypothyroidism (CH) requires elevated plasma FT4-concentrations compared to patients with acquired thyroidal hypothyroidism. We investigated bone mineral density (BMD) in patients with CH. Patients

  6. Neutron crystallographic studies of T4 lysozyme at cryogenic temperature. (United States)

    Li, Le; Shukla, Shantanu; Meilleur, Flora; Standaert, Robert F; Pierce, Josh; Myles, Dean A A; Cuneo, Matthew J


    Bacteriophage T4 lysozyme (T4L) has been used as a paradigm for seminal biophysical studies on protein structure, dynamics, and stability. Approximately 700 mutants of this protein and their respective complexes have been characterized by X-ray crystallography; however, despite the high resolution diffraction limits attained in several studies, no hydrogen atoms were reported being visualized in the electron density maps. To address this, a 2.2 Å-resolution neutron data set was collected at 80 K from a crystal of perdeuterated T4L pseudo-wild type. We describe a near complete atomic structure of T4L, which includes the positions of 1737 hydrogen atoms determined by neutron crystallography. The cryogenic neutron model reveals explicit detail of the hydrogen bonding interactions in the protein, in addition to the protonation states of several important residues. © 2017 The Protein Society.

  7. Brucella T4SS: the VIP pass inside host cells. (United States)

    Lacerda, Thais Lourdes Santos; Salcedo, Suzana Pinto; Gorvel, Jean-Pierre


    For many Gram-negative bacteria, like Brucella, the type IV secretion system (T4SS) has a critical role in bacterial virulence. In Brucella, the VirB T4SS permits the injection of bacterial effectors inside host cells, leading to subversion of signaling pathways and favoring bacterial growth and pathogenesis. The virB operon promoter is tightly regulated by a combination of transcriptional activators and repressors that are expressed according to the environmental conditions encountered by Brucella. Recent advances have shed light on the Brucella T4SS regulatory mechanisms and also its substrates. Characterization of the targets and functions of these translocated effectors is underway and will help understand the role of the T4SS in the establishment of a replication niche inside host cells.

  8. [Inactivation of T4 phage in water environment using proteinase]. (United States)

    Lü, Wen-zhou; Yang, Qing-xiang; Zhang, Yu; Yang, Min; Zhu, Chun-fang


    The inactivation effectiveness of proteinase to viruses was investigated by using T4 phage as a model virus. The results showed that the inactivation effectiveness of proteinase to T4 phage was obvious. In the optimum conditions and 67.5 u/mL concentration, the inactivation rate of proteinase K to T4 phage in sterilized water and in sewage achieved 99.4% and 49.4% respectively in an hour, and achieved >99.9% and 81.1% in three hours. The inactivation rate of the industrial proteinase 1398 to T4 phage in sterilized water achieved 74.4% in an hour. The effects of pH and temperature on the inactivation effectiveness was not evident.

  9. Acanthamoeba T4 genotype associated with keratitis infections in Tunisia. (United States)

    Dendana, F; Sellami, H; Trabelsi, H; Neji, S; Cheikhrouhou, F; Makni, F; Ayadi, A


    Acanthamoeba keratitis (AK) is a sight-threatening infection. We report five cases of AK diagnosed from 2005 to 2009 in the Laboratory of Parasitology-Mycology at Habib Bourguiba Sfax Hospital, Tunisia. All were associated with improper care of contact lenses (rinsing of contact lenses with tap water and inappropriate cleaning) and lens storage. The patients displayed different clinical presentations: corneal inflammation, corneal ulceration, and corneal abscess. The diagnosis was made after direct examination, culture, and polymerase chain reaction amplification with specific primers. The genotype classification was based on the highly variable DF3 region in the 18S rRNA gene. This is the first study characterizing Acanthamoeba genotype in Tunisia and North Africa. All Acanthamoeba isolates were associated to the T4 genotype. Three different DF3 sequence types were related to AK infections T4/10, T4/15, and T4/16.

  10. Changes in the before and after thyroxine treatment levels of adipose tissue, leptin, and resistin in subclinical hypothyroid patients. (United States)

    Akbaba, Gulhan; Berker, Dilek; Isık, Serhat; Tuna, Mazhar Muslum; Koparal, Suha; Vural, Murat; Yılmaz, Fatma Meric; Topcuoglu, Canan; Guler, Serdar


    Subclinical hypothyroidism (SH) occurs when serum thyroid stimulating hormone (TSH) concentrations are raised and serum thyroid hormone concentrations are normal. The effect of SH on the proinflammatory adipose cytokine releasing visceral adipose tissue (VAT) is not clear. The aim of this study is to identify the difference between the pre and posttreatment levels of VAT, leptin, and resistin in SH patients. There were 51 SH patients and 43 age- and gender-matched healthy subjects included in the study. Thyroid functions, biochemical tests, leptin, resistin, and visceral and subcutaneous fat measurements were made. The measurements were repeated in the SH group in the third month following L-thyroxin treatment. Initially, high sensitivity C-reactive protein, carotid artery intima-media thickness (mm), leptin, and resistin levels were significantly higher in the SH group compared to the controls, while the other parameters were similar. While no correlation was observed between TSH levels and adipokines, a positive correlation was detected between waist circumference and leptin levels (r = 0.549, p adipose tissue was positively correlated to age, waist circumference, and leptin levels, but negatively correlated to free thyroxin (T4) levels (r = 0.419, p = 0.009; r = 0.794, p leptin, and resistin levels of SH patients following levothyroxine treatment. Conclusion The reduced VAT volume, leptin, and resistin levels in SH patients following treatment may support the idea that TSH affects adipose tissue functions.

  11. Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure.

    Directory of Open Access Journals (Sweden)

    Olympia Anastasiou

    Full Text Available Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS, have been described in many diseases. However, the relationship between acute liver failure (ALF and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF.84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR. TSH, free thyroxine (fT4, free triiodothyronine (fT3, T4, and T3 were determined.More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression.In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.

  12. Genetic diversity among five T4-like bacteriophages

    Directory of Open Access Journals (Sweden)

    Bertrand Claire


    Full Text Available Abstract Background Bacteriophages are an important repository of genetic diversity. As one of the major constituents of terrestrial biomass, they exert profound effects on the earth's ecology and microbial evolution by mediating horizontal gene transfer between bacteria and controlling their growth. Only limited genomic sequence data are currently available for phages but even this reveals an overwhelming diversity in their gene sequences and genomes. The contribution of the T4-like phages to this overall phage diversity is difficult to assess, since only a few examples of complete genome sequence exist for these phages. Our analysis of five T4-like genomes represents half of the known T4-like genomes in GenBank. Results Here, we have examined in detail the genetic diversity of the genomes of five relatives of bacteriophage T4: the Escherichia coli phages RB43, RB49 and RB69, the Aeromonas salmonicida phage 44RR2.8t (or 44RR and the Aeromonas hydrophila phage Aeh1. Our data define a core set of conserved genes common to these genomes as well as hundreds of additional open reading frames (ORFs that are nonconserved. Although some of these ORFs resemble known genes from bacterial hosts or other phages, most show no significant similarity to any known sequence in the databases. The five genomes analyzed here all have similarities in gene regulation to T4. Sequence motifs resembling T4 early and late consensus promoters were observed in all five genomes. In contrast, only two of these genomes, RB69 and 44RR, showed similarities to T4 middle-mode promoter sequences and to the T4 motA gene product required for their recognition. In addition, we observed that each phage differed in the number and assortment of putative genes encoding host-like metabolic enzymes, tRNA species, and homing endonucleases. Conclusion Our observations suggest that evolution of the T4-like phages has drawn on a highly diverged pool of genes in the microbial world. The T4

  13. Thyroxine lipophilicity is dominated by its zwitterionic microspecies. (United States)

    Mazák, Károly; Tóth, Gergő; Kökösi, József; Noszál, Béla


    Species-specific partition coefficients were determined for a triprotic molecule for the first time. Thyroxine, the vitally important thyroid hormone which exists in solution in the forms of eight microspecies due to its phenolate, amino and carboxylate basic sites, was studied by combined methods of microspeciation and lipophilicity. Partition of the individual microspecies was mimicked by model compounds of the closest possible similarity, then correction factors were determined and introduced. The non-charged microspecies is only 2.40 times as lipophilic as its zwitterionic protonation isomer, showing that for thyroxine the iodinated aromatic rings are the structural elements that determine the lipophilicity of this molecule, and the protonation state of the other substituents plays only a minor role. The overwhelming dominance of the zwitterionic form, however, ensures that its contribution to the overall lipophilicity exceeds 14,500 times that of the non-charged one. This fact is so far the sharpest counter-example of the widespread belief that passive diffusion into lipophilic media is predominated by the non-charged species. The lipophilicity profile of thyroxine is expressed, calculated and depicted in terms of species-specific lipophilicities over the entire pH range. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Circulating thyroxine, thyroid-stimulating hormone, and hypothyroid status and the risk of prostate cancer.

    Directory of Open Access Journals (Sweden)

    Alison M Mondul

    Full Text Available BACKGROUND: Thyroid hormones may influence risk of cancer through their role in cell differentiation, growth, and metabolism. One study of circulating thyroid hormones supports this hypothesis with respect to prostate cancer. We undertook a prospective analysis of thyroid hormones and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC Study. METHODS: Within the ATBC Study, a randomized controlled trial of α-tocopherol and β-carotene supplements and cancer incidence in male smokers, 402 prostate cancer cases were sampled. Controls were matched 2:1 to cases on age and date of blood collection. Odds ratios (OR and 95% confidence intervals (CI of prostate cancer were estimated for quintiles of serum total and free thyroxine (T4, thyroid-stimulating hormone (TSH, thyroid-binding globulin (TBG, and by categories of thyroid status. RESULTS: Men with serum higher TSH had a decreased risk of prostate cancer compared to men with lower TSH (Q5 vs. Q1-4: OR = 0.70, 95% CI: 0.51-0.97, p = 0.03. When the T4 and TSH measurements were combined to define men as hypothyroid, euthyroid or hyperthyroid, hypothyroid men had a lower risk of prostate cancer compared to euthyroid men (OR = 0.48, 95% CI = 0.28-0.81, p = 0.006. We observed no association between hyperthyroid status and risk, although the number of hyperthyroid men with prostate cancer was small (n = 9. CONCLUSIONS: In this prospective study of smokers, men with elevated TSH and those classified as being in a hypothyroid state were at decreased risk of prostate cancer. Future studies should examine the association in other populations, particularly non-smokers and other racial/ethnic groups.

  15. Short-term overt hypothyroidism affect on lipids after thyroxine-withdrawal in patients with differentiated thyroid carcinoma%骨巨细胞瘤软组织内复发两例报道及文献复习

    Institute of Scientific and Technical Information of China (English)

    Hongyu Wu; Shuyao Zuo; Chao Ma; Bin Liu; Fengyu Wu; Simin Liu; Qin Zhang; Xifu Lan


    Objective: The aim of the study was to investigate the effects of short-term overt hypothyroidism on lipids after thyroxine-withdrawal in patients with iatrogenically induced hypothyroidism before radioiodine treatment for differentiated thyroid carcinoma (DTC). Methods: Thirty patients with a history of differentiated thyroid carcinoma on thyroid-stimulating hormone (TSH)-suppressive thyroxine replacement therapy were studied. Blood sample were taken before and 4 weeks after withdrawal of thyroxine substitution. Venous blood was drawn after an overnight fast and analyzed for serum free T4 (FT4), free T3 (FT3), thyroid-stimulating hormone (TSH), total cholesterol (TC), triglyceddes (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB). Fifty healthy people matched for age and gender were controls. Their blood samples were taken only once. Results: After thyroxine-withdrawal, the patients presented with increased serum TSH and low serum FT4 and FT3 levels compared with controls. Serum TG, TC, LDL, HDL, APOB and Lp(a) increased after thyroxine withdrawal, reaching statistical significant dif-ferences with previous evaluation. However, when compared to euthyroid controls, only TC, LDL and ApoB were increased when patients were hypothyroidism. No changes were observed in ApoA1 in patients dudng thyroxine withdrawal, or when comparing the values observed in patients to those of euthyroid controls. Conclusion: TG, TC, LDL, HDL, APO8 and Lp(a) were increased during short-term overt hypothyroidism.

  16. The thyroxine-containing thyroglobulin peptide (aa 2549-2560) is a target epitope in iodide-accelerated spontaneous autoimmune thyroiditis. (United States)

    Kolypetri, Panayota; Carayanniotis, Karen; Rahman, Shofiur; Georghiou, Paris E; Magafa, Vassiliki; Cordopatis, Paul; Carayanniotis, George


    Enhanced iodide ingestion is known to accelerate the incidence and severity of spontaneous autoimmune thyroiditis [iodide-accelerated spontaneous autoimmune thyroiditis (ISAT)] in NOD.H2(h4) mice. CD4+ cells are required for the development and maintenance of ISAT, but their target epitopes remain unknown. In this study, we show that the previously identified thyroglobulin (Tg) T cell epitope p2549-2560 containing thyroxine at position 2553 (T4p2553) induces thyroiditis as well as strong specific T and B cell responses in NOD.H2(h4) mice. In ISAT, activated CD4+ T cells specific for T4p2553 are detected before the disease onset in thyroid-draining cervical lymph nodes only in mice placed on an iodide-rich diet and not in age-matched controls. In addition, selective enrichment of CD4+ IFN-γ+ T4p2553-specific cells is observed among cervical lymph node cells and intrathyroidal lymphocytes. T4p2553 was equally detectable on dendritic cells obtained ex vivo from cervical lymph node cells of NaI-fed or control mice, suggesting that the iodide-rich diet contributes to the activation of autoreactive cells rather than the generation of the autoantigenic epitope. Furthermore, spontaneous T4p2553-specific IgG are not detectable within the strong Tg-specific autoantibody response. To our knowledge, these data identify for the first time a Tg T cell epitope as a spontaneous target in ISAT.

  17. Thyroxine 5'-deiodinase in human anterior pituitary tumors. (United States)

    Itagaki, Y; Yoshida, K; Ikeda, H; Kaise, K; Kaise, N; Yamamoto, M; Sakurada, T; Yoshinaga, K


    The activity of T4 5'-monodeiodinase (5'D) in the pituitary was measured in 12 patients with pituitary adenoma (3 patients with acromegaly, 2 with prolactinoma, 1 with Cushing's disease, 1 with TSH-producing tumor, and 5 with nonfunctioning tumor) and, as a control, in a patient who died of parotid cancer. The pituitaries, obtained at operation or autopsy, were homogenized in 0.1 mol/L potassium phosphate buffer, pH 7.0, and centrifuged at 800 x g. Supernatants were incubated with [125I]T4 and 20 mmol/L dithiothreitol (DTT) at 37C for 90 min. T4 5'-D was measured by the release of 125I- with the ion exchange method. The activity of T4 5'-D in the pituitaries from patients with prolactinoma and parotid cancer was dependent on protein concentration, incubation time, incubation temperature, and T4 concentration, and was labile to prior heating at 70 C for 30 min. T4 5'-D was not inhibited by 1 mmol/L propylthiouracil, but was inhibited 95% by 0.1 mmol/L iopanoic acid. The apparent Km and maximum velocity for T4 5'-D in homogenates of prolactinoma at 20 mmol/L DTT were 11 nmol/L and 1.54 pmol/mg protein.h, respectively. This reaction followed sequential-type reaction kinetics when the DTT concentration was varied. All other homogenates of pituitary tumors, except two nonfunctioning tumors, also demonstrated T4 5'-D activity. These results indicate that 1) the human pituitary express a low Km and PTU-insensitive T4 5'-D activity which is very similar to the type II enzyme activity in the rat pituitary; and 2) various types of pituitary tumor cells contain T4 5'-D activity.

  18. T-4G Methodology: Undergraduate Pilot Training T-37 Phase. (United States)

    Woodruff, Robert R.; And Others

    The report's brief introduction describes the application of T-4G methodology to the T-37 instrument phase of undergraduate pilot training. The methodology is characterized by instruction in trainers, proficiency advancement, a highly structured syllabus, the training manager concept, early exposure to instrument training, and hands-on training.…

  19. Structure and assembly of bacteriophage T4 head

    Directory of Open Access Journals (Sweden)

    Black Lindsay W


    Full Text Available Abstract The bacteriophage T4 capsid is an elongated icosahedron, 120 nm long and 86 nm wide, and is built with three essential proteins; gp23*, which forms the hexagonal capsid lattice, gp24*, which forms pentamers at eleven of the twelve vertices, and gp20, which forms the unique dodecameric portal vertex through which DNA enters during packaging and exits during infection. The past twenty years of research has greatly elevated the understanding of phage T4 head assembly and DNA packaging. The atomic structure of gp24 has been determined. A structural model built for gp23 using its similarity to gp24 showed that the phage T4 major capsid protein has the same fold as that found in phage HK97 and several other icosahedral bacteriophages. Folding of gp23 requires the assistance of two chaperones, the E. coli chaperone GroEL and the phage coded gp23-specific chaperone, gp31. The capsid also contains two non-essential outer capsid proteins, Hoc and Soc, which decorate the capsid surface. The structure of Soc shows two capsid binding sites which, through binding to adjacent gp23 subunits, reinforce the capsid structure. Hoc and Soc have been extensively used in bipartite peptide display libraries and to display pathogen antigens including those from HIV, Neisseria meningitides, Bacillus anthracis, and FMDV. The structure of Ip1*, one of the components of the core, has been determined, which provided insights on how IPs protect T4 genome against the E. coli nucleases that degrade hydroxymethylated and glycosylated T4 DNA. Extensive mutagenesis combined with the atomic structures of the DNA packaging/terminase proteins gp16 and gp17 elucidated the ATPase and nuclease functional motifs involved in DNA translocation and headful DNA cutting. Cryo-EM structure of the T4 packaging machine showed a pentameric motor assembled with gp17 subunits on the portal vertex. Single molecule optical tweezers and fluorescence studies showed that the T4 motor packages

  20. Effects of thyroxine and 1-methyl, 2-mercaptoimidazol on phosphoinositides synthesis in rat liver

    Directory of Open Access Journals (Sweden)

    Krasilnikova Oksana A


    Full Text Available Abstract Background Phosphoinositides mediate one of the intracellular signal transduction pathways and produce a class of second messengers that are involved in the action of hormones and neurotransmitters on target cells. Thyroid hormones are well known regulators of lipid metabolism and modulators of signal transduction in cells. However, little is known about phosphoinositides cycle regulation by thyroid hormones. The present paper deals with phosphoinositides synthesis de novo and acylation in liver at different thyroid status of rats. Results The experiments were performed in either the rat liver or hepatocytes of 90- and 720-day-old rats. Myo-[3H]inositol, [14C]CH3COONa, [14C]oleic and [3H]arachidonic acids were used to investigate the phosphatidylinositol (PtdIns, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate (PtdInsP2 synthesis. 1-methyl, 2-mercaptoimidazol-induced hypothyroidism was associated with the decrease of myo-[3H]inositol and [3H]arachidonic acids incorporation into liver phosphoinositides and total phospholipids, respectively. The thyroxine (L-T4 injection to hypothyroid animals increased the hormones contents in blood serum and PtdInsP2 synthesis de novo as well as [3H]arachidonic acids incorporation into the PtdIns and PtdInsP2. Under the hormone action, the [14C]oleic acid incorporation into PtdIns reduced in the liver of hypothyroid animals. A single injection of L-T4 to the euthyroid [14C]CH3COONa-pre-treated animals or addition of the hormone to a culture medium of hepatocytes was accompanied by the rapid prominent increase in the levels of the newly synthesized PtdIns and PtdInsP2 and in the mass of phosphatidic acid in the liver or the cells. Conclusions The data obtained have demonstrated that thyroid hormones are of vital importance in the regulation of arachidonate-containing phosphoinositides metabolism in the liver. The drug-induced malfunction of thyroid gland noticeably changed the

  1. Metabolism of thyroxine in Rana catesbeiana tadpoles during metamorphic climax

    Energy Technology Data Exchange (ETDEWEB)

    Galton, V.A.; Munck, K.


    Previous studies have indicated that premetamorphic tadpoles do not convert T4 to T3 to a measurable extent (1). The present study was performed to determine whether a T4 5'-monodeiodinating system is acquired at later stages of development. (/sup 125/I)T4 metabolism in vivo was determined in tadpoles at most stages of prometamorphosis and metamorphic climax and, for comparison, in premetamorphic tadpoles. The conversion of (/sup 125/I)T4 to (/sup 125/I)T3, as indicated by the presence of an /sup 125/I-labeled product in serum and liver preparations that cochromatographed with carrier T3, was sometimes observed in tadpoles near the end of prometamorphosis and was always evident in tadpoles that were either undergoing or had completed metamorphic climax. However, during this phase, no correlation could be drawn between the extent of T3 production and morphological development. The formation of T3 from T4 in vivo was significantly decreased in tadpoles pretreated with propylthiouracil. The T45'-monodeiodinating system could be induced in premetamorphic tadpoles by injecting them with either T4 or T3. This finding together with the observation that normal acquisition of this system occurs at the time when endogenous T4 and T3 levels are rising rapidly suggest that its development is under the control of the thyroid hormones.

  2. T4/T8 ratio and absolute T4 cell numbers in different clinical stages of Kaposi's sarcoma in AIDS. (United States)

    Spornraft, P; Fröschl, M; Ring, J; Meurer, M; Goebel, F D; Ziegler-Heitbrock, H W; Riethmüller, G; Braun-Falco, O


    Thirty-seven men (36 homosexual or bisexual and one heterosexual) with epidemic Kaposi's sarcoma and underlying HIV infection were followed up over a period of up to 32 months. Fourteen patients (38%) died, with a median survival time of 7.2 months after the diagnosis of AIDS. Seventeen patients (46%) presented with one or more opportunistic infections, mostly Pneumocystis carinii pneumonia. Eighteen patients (49%) had lymphadenopathy syndrome according to the definition of the CDC. Using the Laubenstein-classification of Kaposi's sarcoma, all patients either remained stable or deteriorated, improvement was never observed. Absolute T4 lymphocyte counts and the T4/T8 ratio were not related to the disease stage. With the onset of B symptoms (systemic symptoms), however, the absolute T4 numbers and the T4/T8 ratio markedly decreased. Delayed type hypersensitivity also showed no relationship to the clinical stages of Kaposi's sarcoma. Thus, the clinical progression of Kaposi's sarcoma lesions seems to be largely independent of the immunological parameters investigated. However, the onset of B symptoms was observed to be related to changes in immune status.

  3. LPS-activated monocytes are unresponsive to T4 phage and T4-generated Escherichia coli lysate

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    Katarzyna Bocian


    Full Text Available A growing body of data shows that bacteriophages can interact with different kinds of immune cells. The objective of this study was to investigate whether T4 bacteriophage and T4-generated Escherichia coli lysate affect functions of monocytes, the key population of immune cells involved in antibacterial immunity. To that end we evaluated how T4 and E. coli lysate influence the expression of main costimulatory molecules including CD40, CD80 and CD86, TLR2, TLR4 on monocytes, as well as the production of IL-6 and IL-12 in cultures of peripheral blood mononuclear cells (PBMCs. Separate experiments were performed on unactivated and LPS-activated PBMCs cultures. Both studied preparations significantly increased the percentage of CD14+CD16-CD40+ and CD14+CD16-CD80+ monocytes in unactivated PBMCs cultures, as well as the concentration of IL-6 and IL-12 in culture supernates. However, neither purified T4 nor E. coli lysate had any significant effect on monocytes in LPS-activated PBMCs cultures. We conclude that LPS-activated monocytes are unresponsive to phages and products of phage-induced lysis of bacteria. This study is highly relevant to phage therapy because it suggests that in patients with infections caused by Gram-negative bacteria the administration of phage preparations to patients and lysis of bacteria by phages are not likely to overly stimulate monocytes.

  4. Interplay between thyroxin, BDNF and GABA in injured neurons. (United States)

    Shulga, A; Rivera, C


    Accumulating experimental evidence suggests that groups of neurons in the CNS might react to pathological insults by activating developmental-like programs for survival, regeneration and re-establishment of lost connections. For instance, in cell and animal models it was shown that after trauma mature central neurons become dependent on brain-derived neurotrophic factor (BDNF) trophic support for survival. This event is preceded by a shift of postsynaptic GABAA receptor-mediated responses from hyperpolarization to developmental-like depolarization. These profound functional changes in GABAA receptor-mediated transmission and the requirement of injured neurons for BDNF trophic support are interdependent. Thyroid hormones (THs) play a crucial role in the development of the nervous system, having significant effects on dendritic branching, synaptogenesis and axonal growth to name a few. In the adult nervous system TH thyroxin has been shown to have a neuroprotective effect and to promote regeneration in experimental trauma models. Interestingly, after trauma there is a qualitative change in the regulatory effect of thyroxin on BDNF expression as well as on GABAergic transmission. In this review we provide an overview of the post-traumatic changes in these signaling systems and discuss the potential significance of their interactions for the development of novel therapeutic strategies.

  5. Decrease of free thyroxine levels after controlled ovarian hyperstimulation

    NARCIS (Netherlands)

    A.F. Muller (Alex); A. Verhoeff; M.J. Mantel; F.H. de Jong (Frank); A. Berghout (Arie)


    textabstractControlled ovarian hyperstimulation could lead to opposing effects on thyroid function. Therefore, in a prospective study of 65 women undergoing controlled ovarian hyperstimulation, thyroid hormones, T4-binding globulin, TPO antibodies, gonadotropins, estrad

  6. Evaluation of virus removal in MBR using coliphages T4

    Institute of Scientific and Technical Information of China (English)

    ZHENG Xiang; Lü Wenzhou; YANG Min; LIU Junxin


    A membrane bioreactor (MBR) with gravity drain was tested for domestic wastewater for 65 days. Results showed that the effluent quality was excellent, and met with the reuse water standard of China (GB/T 18920-2002). Virus removal in the membrane separation process was investigated by employing coliphages T4 as a tracer. Two microfiltration membrane modules, with pore sizes of 0.22 and 0.1 μm, were used to investigate their effects on virus rejection at the transmembrane pressure of 8.5 kPa. It was found that 0.1 μm membrane had complete rejection of virus, and 0.22 μm membrane had significant rejection of virus. In the long- term operation of this MBR, no significant difference was observed between both pore sizes because the virus concentrations of the effluent in both cases were in the same order. Effluent virus concentration at steady state of MBR running was less than 2 PFU/mL. The removal ratios of coliphage T4 in MF processes were more than 105.5. The membrane surface deposits played an important role in the rejection of virus. The formation of cake clay on the membrane surface was the main cause of high rejection of coliphage T4 with MF of 0.22 μm.

  7. Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats

    Directory of Open Access Journals (Sweden)

    Chen Yue-Feng


    Full Text Available Abstract Background Left ventricular (LV remodeling following large transmural myocardial infarction (MI remains a pivotal clinical issue despite the advance of medical treatment over the past few decades. Identification of new medications to improve the remodeling process and prevent progression to heart failure after MI is critical. Thyroid hormones (THs have been shown to improve LV function and remodeling in animals post-MI and in the human setting. However, changes in underlying cellular remodeling resulting from TH treatment are not clear. Methods MI was produced in adult female Sprague–Dawley rats by ligation of the left descending coronary artery. L-thyroxine (T4 pellet (3.3 mg, 60 days sustained release was used to treat MI rats for 8 weeks. Isolated myocyte shape, arterioles, and collagen deposition in the non-infarcted area were measured at terminal study. Results T4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte cross-sectional area without further increasing myocyte length in MI rats. T4 treatment increased the total LV tissue area by 34%, increased the non-infarcted tissue area by 41%, and increased the thickness of non-infarcted area by 36% in MI rats. However, myocyte volume accounted for only ~1/3 of the increase in myocyte mass in the non-infarct area, indicating the presence of more myocytes with treatment. T4 treatment tended to increase the total length of smaller arterioles (5 to 15 μm proportional to LV weight increase and also decreased collagen deposition in the LV non-infarcted area. A tendency for increased metalloproteinase-2 (MMP-2 expression and tissue inhibitor of metalloproteinases (TIMPs -1 to −4 expression was also observed in T4 treated MI rats. Conclusions These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in

  8. Influence of adsorption and deproteination on potential free thyroxine reference methods

    DEFF Research Database (Denmark)

    Holm, Steen S; Andreasen, Lisbeth; Hansen, Palle Steen;


    There is a need for consensus concerning reference methods to be used for calibration of commercial free-thyroxine (FT(4)) assays.......There is a need for consensus concerning reference methods to be used for calibration of commercial free-thyroxine (FT(4)) assays....

  9. T4 genes in the marine ecosystem: studies of the T4-like cyanophages and their role in marine ecology. (United States)

    Clokie, Martha R J; Millard, Andrew D; Mann, Nicholas H


    From genomic sequencing it has become apparent that the marine cyanomyoviruses capable of infecting strains of unicellular cyanobacteria assigned to the genera Synechococcus and Prochlorococcus are not only morphologically similar to T4, but are also genetically related, typically sharing some 40-48 genes. The large majority of these common genes are the same in all marine cyanomyoviruses so far characterized. Given the fundamental physiological differences between marine unicellular cyanobacteria and heterotrophic hosts of T4-like phages it is not surprising that the study of cyanomyoviruses has revealed novel and fascinating facets of the phage-host relationship. One of the most interesting features of the marine cyanomyoviruses is their possession of a number of genes that are clearly of host origin such as those involved in photosynthesis, like the psbA gene that encodes a core component of the photosystem II reaction centre. Other host-derived genes encode enzymes involved in carbon metabolism, phosphate acquisition and ppGpp metabolism. The impact of these host-derived genes on phage fitness has still largely to be assessed and represents one of the most important topics in the study of this group of T4-like phages in the laboratory. However, these phages are also of considerable environmental significance by virtue of their impact on key contributors to oceanic primary production and the true extent and nature of this impact has still to be accurately assessed.

  10. T4 genes in the marine ecosystem: studies of the T4-like cyanophages and their role in marine ecology

    Directory of Open Access Journals (Sweden)

    Millard Andrew D


    Full Text Available Abstract From genomic sequencing it has become apparent that the marine cyanomyoviruses capable of infecting strains of unicellular cyanobacteria assigned to the genera Synechococcus and Prochlorococcus are not only morphologically similar to T4, but are also genetically related, typically sharing some 40-48 genes. The large majority of these common genes are the same in all marine cyanomyoviruses so far characterized. Given the fundamental physiological differences between marine unicellular cyanobacteria and heterotrophic hosts of T4-like phages it is not surprising that the study of cyanomyoviruses has revealed novel and fascinating facets of the phage-host relationship. One of the most interesting features of the marine cyanomyoviruses is their possession of a number of genes that are clearly of host origin such as those involved in photosynthesis, like the psbA gene that encodes a core component of the photosystem II reaction centre. Other host-derived genes encode enzymes involved in carbon metabolism, phosphate acquisition and ppGpp metabolism. The impact of these host-derived genes on phage fitness has still largely to be assessed and represents one of the most important topics in the study of this group of T4-like phages in the laboratory. However, these phages are also of considerable environmental significance by virtue of their impact on key contributors to oceanic primary production and the true extent and nature of this impact has still to be accurately assessed.

  11. Defending plasma T3 is a biological priority. (United States)

    Abdalla, Sherine M; Bianco, Antonio C


    Triiodothyronine (T3), the active form of thyroid hormone is produced predominantly outside the thyroid parenchyma secondary to peripheral tissue deiodination of thyroxine (T4), with thyroid. In healthy individuals, plasma T3 is regulated by the negative feedback loop of the hypothalamus-pituitary-thyroid axis and by homoeostatic changes in deiodinase expression. Therefore, with the exception of a minimal circadian rhythmicity, serum T3 levels are stable over long periods of time. Studies in rodents indicate that different levels of genetic disruption of the feedback mechanism and deiodinase system are met with increase in serum T4 and thyroid-stimulating hormone (TSH) levels, while serum T3 levels remain stable. These findings have focused attention on serum T3 levels in patients with thyroid disease, with important clinical implications affecting therapeutic goals and choice of therapy for patients with hypothyroidism. Although monotherapy with levothyroxine is the standard of care for hypothyroidism, not all patients normalize serum T3 levels with many advocating for combination therapy with levothyroxine and liothyronine. The latter could be relevant for a significant number of patients that remain symptomatic on monotherapy with levothyroxine, despite normalization of serum TSH levels. © 2014 John Wiley & Sons Ltd.

  12. Local and systemic alterations in cyclic 3',5' AMP phosphodiesterase activity in relation to tail regeneration under hypothyroidism and T4 replacement in the lizard, Mabuya carinata. (United States)

    Ramachandran, A V; Swamy, M S; Kurup, A K


    To establish the relationship between thyroid hormone and cyclic Adenosine monophosphate (cAMP) during lacertilian tail regeneration, cAMP phosphodiesterase, the hydrolytic enzyme of cAMP, was assayed in the tail regenerate, liver, and skeletal muscle of control (group A), chemically thyroidectomized (group B), and thyroidectomized and T4-replaced (group C) animals during various periods of tail regeneration. Enzyme activity was elevated in all three tissues of group B animals. Animals of group C showed an intermediate level of enzyme activity between controls (group A) and experimental animals (group B). These observations suggest a possible regulatory role of thyroxine in maintaining optimum levels of phosphodiesterase. The retardation in regeneration observable in the hypothyroid group of animals may be correlated with low levels of tissue cAMP. However, the operation of other influencing factors on phosphodiesterase during regeneration can be surmised from the observed tendency to exhibit similar patterns of phase-specific modulations in enzyme activity. Our observations are discussed in terms of phase-specific involvement of cAMP in regeneration, as well as its role in other metabolic aspects and the possible mode of indirect control exerted by thyroxine on lacertilian tail regeneration.

  13. Oophorectomy did not show any additional effect on bone density and mineral content in thyroxine treated mice. (United States)

    Broulik, P D; Pacovský, V; Límanová, Z


    Experimental hyperthyroidism (thyroxine administration for 21 days) caused a significant decrease in ash mass, bone density and mineral content in the femora of mice, the same degree of reduction in individual measures of bone mass being found in oophorectomized and intact mice treated with thyroxine. It may be suggested that estrogens did not protect the skeleton against the resorbing action of thyroxine or triiodothyronine.

  14. Empenamento, níveis hormonais de triiodotironina e tiroxina e temperatura corporal de frangos de corte de diferentes genótipos criados em diferentes condições de temperatura Feathering, triiodothyronine and thyroxine plasma levels and body temperature of two broiler lines raised under different temperatures

    Directory of Open Access Journals (Sweden)

    Fabiano Dahlke


    Full Text Available Estudou-se o empenamento, os níveis hormonais de Triiodotironina (T3 e Tiroxina (T4 e a temperatura corporal de frangos criados em diferentes temperaturas. Foram alojados 180 pintainhos Cobb 500 e 180 pintainhos ISA Label JA57, em temperaturas termoneutra, quente ou fria. O delineamento utilizado foi inteiramente ao acaso, em modelo fatorial 2 x 3 (2 linhagens e 3 temperaturas com 8 repetições. Houve um aumento das concentrações de T3, nas aves criadas no frio, e uma redução no calor. Também no calor, os frangos ISA Label apresentaram níveis mais altos de T4. As aves Cobb apresentaram uma redução de T4 no calor ou no frio aos 42 dias e no calor aos 21 dias de idade. Houve menor empenamento aos 42 dias, quando os frangos foram criados em alta temperatura e um menor empenamento das aves ISA Label, quando comparadas aos frangos Cobb. As aves criadas no calor apresentaram maior temperatura corporal. Os frangos Cobb apresentaram um aumento na sua temperatura interna, quando criados em ambiente quente. Já os frangos da linhagem ISA Label mantiveram sua temperatura interna, independentemente da temperatura ambiente. É possível concluir que a temperatura ambiente afeta o empenamento dos frangos de corte de linhagens de rápido ganho de peso, que também apresentaram menor tolerância ao calor, demonstrada através de uma maior temperatura corporal e temperatura interna.Feather growth, plasmatic levels of T3 and T4 and body temperature were evaluated in broiler raised under different temperatures. The two evaluated broiler lines were Cobb-500 and ISA-Label JA57. One hundred and eighty birds of each line were raised under cold, neutral or hot temperatures in a complete randomized design with 3 x 2 factorial scheme (3 temperatures and 2 lines, with 8 repetitions. There was a significant increase in T3 levels of birds raised under cold temperature but, under hot temperature, these levels decresed. Under high temperatures, ISA Label birds

  15. Synthesis of a highly fluorescent beta-diketone-europium chelate and its utility in time-resolved fluoroimmunoassay of serum total thyroxine. (United States)

    Wu, Feng-Bo; Han, Shi-Quan; Zhang, Chao; He, You-Feng


    A new highly fluorescent beta-diketone-europium chelate was synthesized and employed as a tracer to develop a time-resolved fluoroimmunoassay (TRFIA) for detection of serum total thyroxine (T4). The tetradentate beta-diketone chelator, 1,10-bis(thiophene-2'-yl)-4,4,5,5,6,6,7,7-octafluorodecane-1,3,8,10-tetraone (BTOT), was structurally composed of two units of thenoyltrifluoroacetone (TTA) derivatives but expressed fluorescence that was greatly enhanced, as compared to the original TTA molecules, in the presence of excess amount of Eu3+. The luminescence properties of the europium chelate of BTOT werestudied in aqueous solution. Chlorosulfonylation of BTOT afforded 1, 10-bis(5'-chlorosulfo-thiophene-2'-yl)-4,4,5,5,6,6,7,7-octafluorodecane-1,3,8,10-tetraone (BCTOT), which could be coupled to proteins (i.e., streptavidin or the BSA-T4 conjugate) and used as a tracer for TRFIA. Although the BCTOT-Eu complex could be detected at a very low level (approximately 1.07 x 10(-12) mol/L) in buffered aqueous solution (50 mmoVLTris-HCl; pH, 8.0), the application of the chelate label in direct serum T4 TRFIA experienced a problem of matrix interference, which was probably caused by some unknown chelating components in the samples as a result of the fact that the fluorescence of the BCTOT-Eu chelate was prone to quenching or enhancement by some chelating reagents. To remove this problem, an indirect serum T4 TRFIA was proposed with the use of BCTOT-Eu-labeled streptavidin (SA) as signal generation reagent. The concentrations of T4 in 27 human serums were determined by indirect T4 TRFIA, and the assay results correlated well with those obtained by commercial Coming-CLIA (r = 0.955) and Wallac-DELFIA (r 0.965).

  16. Pituitary hyperplasia: a complication of the pseudomalabsorption of thyroxine

    Directory of Open Access Journals (Sweden)

    Doyle MA


    Full Text Available Mary-Anne Doyle, Heather A Lochnan Division of Endocrinology, University of Ottawa, Ottawa, ON, Canada Objective: “The pseudomalabsorption of thyroxine” has been used to describe patients with hypothyroidism who fail to comply with their treatment. We describe a unique case of a 32-year-old with hypothyroidism who developed pituitary hyperplasia and hyperprolactinemia secondary to the pseudomalabsorption of thyroxine. Investigations and treatment: After baseline thyroid-function tests were performed, the patient was administered levothyroxine 0.5 mg under the supervision of a registered nurse. Thyroid function testing was repeated at 30, 60, 120, and 180 minutes. Arrangements were made for further daily supervised loading of levothyroxine 0.1 mg. Results: With the administration of 0.5 mg levothyroxine, free thyroxine levels increased by 120 minutes, and with daily supervised dosing of 0.1 mg there was normalization of the thyroid hormone levels and a reduction of thyroid-stimulating hormone levels. Maintenance of thyroid-stimulating hormone < 15 mU/L for 2 weeks led to a reduction in prolactin levels and regression in the size of the pituitary on magnetic resonance imaging. Conclusion: If left untreated, these patients face significant morbidity and are at risk of developing pituitary hyperplasia, complications from an increase in pituitary size, hyperprolactinemia, and potentially myxedema coma. Recognizing pituitary hyperplasia and hyperprolactinemia as a complication from the pseudomalabsorption of levothyroxine may prevent the potential of a misdiagnosis of a prolactinoma leading to unnecessary investigations and inappropriate treatment. Patient awareness of this serious complication and the rapid, demonstrable resolution with adequate thyroid hormone replacement may provide motivation to comply with supervised dosing of levothyroxine. It has also been suggested that supervised treatment enables the individual to maintain their patient

  17. Thyroxine signal transduction in liver cells involves phospholipase C and phospholipase D activation. Genomic independent action of thyroid hormone

    Directory of Open Access Journals (Sweden)

    Krasilnikova Oksana A


    Full Text Available Abstract Background Numerous investigations demonstrate a novel role of thyroid hormone as a modulator of signal transduction. Protein kinase C (PKC is critical to the mechanism by which thyroid hormones potentiate both the antiviral and immunomodulatory actions of IFNγ in different cells and regulate the exchange of signalling phospholipids in hepatocytes. Because nothing is known about accumulation of PKC modulator - diacylglycerol in cells treated with T4, we examined the nongenomic effect of thyroid hormones on DAG formation and phospholipase activation in liver cells. Results The results obtained provide the first demonstration of phospholipase C, phospholipase D and protein kinase C nongenomic activation and diacylglycerol (DAG accumulation by L-T4 in liver cells. The experiments were performed in either the [14C]CH3COOH-labeled rat liver slices or isolated hepatocytes pre-labeled by [14C]oleic acid. L-T4 activates the DAG production in a concentration- and time-dependent manner. DAG formation in stimulated cells is biphasic and short-lived event: there is an initial, rapid rise in DAG concentration and then a slower accumulation that can be sustained for a few minutes. The early phase of L-T4 generated DAG only is accompanied by phosphatidylinositol 4,5-bisphosphate level decrease and inositol 1,4,5-trisphosphate formation while the second phase is abolished by PKC inhibitor l,(5-isoquinolinesulphonyl2methylpiperasine dihydrochloride (H7 and propranolol. The second phase of DAG production is accompanied by free choline release, phosphatidylcholine content drop and phosphatidylethanol (Peth formation. Inhibitor of phospholipase-C-dependent phosphoinositide hydrolysis, neomycin sulfate, reduced the Peth as well as the DAG response to L-T4. Conclusions The present data have indicated the DAG signaling in thyroid hormone-stimulated liver cells. L-thyroxine activates a dual phospholipase pathway in a sequential and synchronized manner

  18. [Once weekly L-thyroxine treatment in non-compliance: A case report]. (United States)

    Oliver, C; Grino, M; Moatti Vacher-Coponat, P; Morange, I; Retornaz, F


    The non-adherence to substitutive treatment by L-thyroxine is the main cause of the discordance between high thyrotropin values and high doses of the drug. In a 36-year-old patient with post-surgery hypothyroidism, thyrotropin values ranged between 100 and 400 mUI/L, although daily replacement therapy included 300 μg of L-thyroxine and 75 μg of L-triiodothyronine. The oral loading test with L-thyroxine was normal and thyrotropin serum level returned to normal values under weekly oral administration of 1000 μg L-thyroxine. The strategy of non-adherence treatment in hypothyroidism is well defined with oral testing of L-thyroxine, followed by oral or parenteral weekly administration of the drug. The L-thyroxine oral test is the gold standard for diagnosis after eliminating of the other conventional causes: drug interactions or digestive malabsorption. L-thyroxine treatment should be discussed on a case-by-case basis, either daily under surveillance or once weekly oral or parenteral high dose. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  19. The Relationship Between Thyroxine Level and Short Term Clinical Outcome Among Sick Newborn Infants

    Directory of Open Access Journals (Sweden)

    Maliheh Kadivar


    Full Text Available Premature and critically sick infants frequently experience several interventions, including blood transfusions, parentral nutrition, and prescriptions during hospitalization that could affect the result of thyroid function test. This study aims to investigate the correlation between thyroxine level and clinical short term outcome among the newborn infants in the neonatal intensive care unit (NICU. We assessed serum levels of thyroxine and thyroid stimulating hormone of 99 neonates who were admitted in the NICU from September 1st 2004 to March 30th 2005. Number of patients with low thyroxin level (less than 6.5 µg/dl was determined and the relation between serum total thyroxine level and birth weight, gestational age, duration of hospitalization, clinical diagnosis, and final outcome was investigated. Short term outcome was considered as duration of hospitalization and discharge alive from hospital. Prevalence of hypothyroxinemia was 26 percent. Later assessment of thyroxine level within 3 weeks revealed normal level of this parameter (8.12 µg/dl ±1.36. Patients with lower gestational age and lower birth weight had lower thyroxine level (7.15 µg/dl ±2.56, and P=0.03, 6.72 µg/dl ±3.03, and P=0.08. Low thyroxine level was not associated with adverse short-term clinical outcome (mortality rates; 3(11% and 9(12%, and duration of hospitalization among 17.7±9.8 vs 16.7± 13.0 in patients with hypothyroxinemia and low thyroxine level respectively. Hypothyroxinemia has considerable prevalence in neonatal intensive care setting and is related with lower birth weight and gestational age. Whether thyroxin levels are a marker or mediator of short term clinical outcome remains to be determined by further studies.

  20. Distribution of /sup 125/I-thyroxine in different organs and tissues of dietically obese rats

    Energy Technology Data Exchange (ETDEWEB)

    Hartmann, K.; Voss, C.; Huebner, G. (Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic)); Weber, A. (Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic). Radiologische Klinik)


    The distribution of /sup 125/I-thyroxine (% dose/g tissue; tissue/plasma radioactivity ratio) was investigated in different tissues of 28-week-old obese Wistar rats. Obesity was induced by high-fat diet (HFD) and confirmed by carcass analysis; in heavy obese animals the relative and absolute fat content is increased twofold and threefold, respectively, compared to control rats fed on a low-fat diet (LFD). Heavy HFD rats exhibit diminished /sup 125/I-T/sub 4/ distribution in the 'slow pool' (fat tissue, muscle) and unchanged values in the 'fast pool' (liver, kidneys) in comparison with LFD rats with low body weight. The differences in distribution presented here are not caused by the diet per se, but they are the consequence of the obesity of the animal, because no differences in the /sup 125/I-T/sub 4/ distribution were found in the /sup 125/I-T/sub 4/ between HFD and LFD rats with relatively equal body weight and body composition. The reduced T/sub 4/ distribution in the fat tissue of obese rats is discussed in connection with possibly decreased lipolysis in this tissue and possible causal participation in the beginning of obesity.

  1. Isolation and characterization of bacteriophage T4 base plates. (United States)

    Poglazov, B F; Rodikova, L P; Sultanova, R A


    A method for isolating bacteriophage T4 base plates from lysates of Escherichia coli B cells infected with the ts mutant in gene 19, ts B31 has been developed. By electrophoresis in polyacrylamide gel with sodium dodecyl sulfate the base plates have been shown to contain five to seven protein components with molecular weights of 36,000, 53,000, 66,000, 81,000, 87,000, and probably about 100,000. Electron microscope studies have demonstrated that base plates may occur in two structural states: in the form of hexagons or stars. Star rays and short fibrils are not radial or elongated and are turned sideways at an angle to the radius. Base plates do not complement in vitro with free tail cores isolated after disintegration of particles of the wild-type bacteriophage.

  2. Pathogenic assays of acanthamoeba belonging to the t4 genotype.

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    Hamed Mirjalali


    Full Text Available Acanthamoeba genus is introduced as opportunistic and cosmopolitan parasite. Monkey and wistar rat are appropriate models for experimental study on Acanthamoeba infection. In this study Acanthamoeba spp. were isolated from hot spring (HS, windows dust (WD and a corneal sample of keratitis patient (KP and their pathogenicity surveyed by in vitro and in vivo tests.Isolates of Acanthamoeba were cultivated axenically for 12 months in PYG medium. Overall, 30 wistar rats, in 6 equal groups were used for developing experimental Acanthamoeba keratitis (AK and Granulomatous Amoebic Encephalitis (GAE. The Keratitis and Granulomatous Encephalitis experiments were performed by intrastromal and intranasal inoculation of Acanthamoeba cysts, respectively. Pathogenicity of the three isolates was also evaluated by in vitro test using osmotolerance and temperature tolerance assays. Identification of genotypes were performed by PCR technique and sequencing.None of the isolates could perform AK and GAE in wistar rats, although all isolates were described as T4 genotype. Isolates obtained from KP and WD could grow only in 30 °C, but not in 37 °C and 40 °C. On the other hand, HS isolate grew in 30 °C and 37 °C but not in 40 °C. Moreover, all of isolate grew in 0.5 M mannitol but not in 1 M and 1.5 M.T4 isolates with a long-term axenic culture and different factors related to host and parasite may play role in pathogenicity of these free-living amoebae.

  3. Effect on pathogenesis of Keshan disease by change of thyroxine 5’—monodeiodinase activity.

    Institute of Scientific and Technical Information of China (English)


    In this paper, writers investigate the activities of myocardial hepatic and renal thyroxine 5’—monodeiodinase of rats fed with grains from a KD endemic area. The results showed that myocardial ,hepatic and renal

  4. Clinical significance of the measurements of serum free thyroxine and free triiodothyronine concentrations. Evaluation using DPC free T/sub 4/ and free T/sub 3/ kits

    Energy Technology Data Exchange (ETDEWEB)

    Kubota, Ken; Sasaki, Norio; Takaku, Fumimaro; Uchimura, Hidemasa


    A commercially available ''DPC'' radioimmunoassay kit was used to study the serum concentrations of free triiodothyronine (FT3) and free thyroxine (FT4) in a series of 189 patients with various thyroid diseases and 120 healthy controls. The basal serum concentrations of FT3 and FT4 in normal controls ranged from 0.98 to 2.04 ng/dl and from 1.43 to 3.66 pg/ml, respectively. All untreated patients with Graves' disease had abnormally high FT3 and FT4 values, indicating the discrimination between hyperthyroid and normal subjects. A decreased ratio of FT4 to FT3 was observed in patients managed with antithyroid drugs. In diagnosing hypothyroidism, ''DPC'' FT4 kits were more sensitive than ''DPC'' TT4 and ''Amerlex'' FT4 kits. In the case of non-thyroid diseases, FT4 and FT3 values, as well as total T4 and total T3, were normal or decreased, with the exception of occasionally unknown high values. The interference of thyroxine binding globulin abnormablity was successfully eliminated by using new versions of ''DPC'' kits. (Namekawa, K.).

  5. Linear growth, growth-hormone secretion and IGF-I generation in children with neglected hypothyroidism before and after thyroxine replacement. (United States)

    Soliman, Ashraf T; Omar, Magdy; El Awwa, Ahmad; Rizk, Mostafa M; El Alaily, Rania K; Bedair, Elsaid M A


    We studied growth hormone (GH) stimulation and insulin-like growth factor -I (IGF-I) generation tests in 15 children with neglected congenital hypothyroidism (CH) (age = 6.4 +/- 4.2 years) and measured their growth parameters for >1 years after starting thyroxine (T4) replacement. One year after treatment, height SDS (HtSDS) increased from -4.3 +/- 2.5 to -2.7 +/- 2.3. Peak GH response to clonidine increased from 3.2 +/- 1.2 ng ml(-1) to 7.62 +/- 1.38 ng ml(-1) after treatments. Basal and peak IGF-I response to GH increased from (34.66 +/- 17.3 ng ml(-1) and 58.4 +/- 36.99 ng ml(-1), respectively) before treatment to (130.6 +/- 97.8 ng ml(-1) and 193.75 +/- 122.5 ng ml(-1), respectively). HtSDS increments were correlated significantly with basal free T4 concentrations (r = 0.622, P < 0.01). In summary, after long period of hypothyroidism, T4 replacement produced significant, although incomplete, catch-up growth through a partial recovery of GH- IGF-I axis.

  6. Cancer cell gene expression modulated from plasma membrane integrin αvβ3 by thyroid hormone and nanoparticulate tetrac

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    Paul eDavis


    Full Text Available Integrin αvβ3 is generously expressed by cancer cells and rapidly dividing endothelial cells. The principal ligands of the integrin are extracellular matrix proteins, but we have described a cell surface small molecule receptor on αvβ3 that specifically binds thyroid hormone and thyroid hormone analogues. From this receptor, thyroid hormone (L-thyroxine, T4; 3,5,3’-triiodo-L-thyronine, T3 and tetraiodothyroacetic acid (tetrac regulate expression of specific genes by a mechanism that is initiated nongenomically. At the integrin, T4 and T3 at physiological concentrations are pro-angiogenic by multiple mechanisms that include gene expression, and T4 supports tumor cell proliferation. Tetrac blocks the transcriptional activities directed by T4 and T3 at αvβ3, but, independently of T4 and T3, tetrac modulates transcription of cancer cell genes that are important to cell survival pathways, control of the cell cycle, angiogenesis, apoptosis, cell export of chemotherapeutic agents and repair of double-strand DNA breaks. We have covalently bound tetrac to a 200 nm biodegradable nanoparticle that prohibits cell entry of tetrac and limits its action to the hormone receptor on the extracellular domain of plasma membrane αvβ3. This reformulation has greater potency than unmodified tetrac at the integrin and affects a broader range of cancer-relevant genes. In addition to these actions on intracellular kinase-mediated regulation of gene expression, hormone analogues at αvβ3 have additional effects on intracellular protein-trafficking (cytosol compartment to nucleus, nucleoprotein phosphorylation and generation of nuclear coactivator complexes that are relevant to traditional genomic actions of T3. Thus, previously unrecognized cell surface-initiated actions of thyroid hormone and tetrac formulations at αvβ3 offer opportunities to regulate angiogenesis and multiple aspects of cancer cell behavior.

  7. First experience with a new principle for measurement of free serum thyroxine

    Energy Technology Data Exchange (ETDEWEB)

    Klingler, W.; Ball, P.; Knuppen, R.


    A new test principle for direct measurement of free thyroxine in serum was investigated the technical handling being remarkably simple. In 257 patients (169 euthyroid, 34 hypothyroid, 20 hyperthyroid, 11 pregnant women, 23 newborns) free thyroxine was measured resulting in a normal range of 6.9-18.5 pg/ml. The correlation between fT/sub 4/ and T/sub 4//TBG-ratio was 0.8207.

  8. Fasting plasma hormones and metabolites in feral and domestic newborn pigs. (United States)

    Kasser, T R; Martin, R J; Gahagan, J H; Wangsness, P J


    Newborn Yorkshire and Ossabaw (feral) pigs were examined under thermoneutral conditions to determine whether survival rate during fasting differs between these breeds and whether any blood-borne factors are associated with improved survival. Newborn pigs were removed from the sow before suckling. Body composition was determined on 10 newborn Ossabaw and 12 newborn Yorkshire pigs. Another group of animals (eight Ossabaw, 12 Yorkshire) was fasted for 72 hr, with blood samples drawn at birth and 12 and 24 hr into fasting. Glucose, free fatty acid (FFA), growth hormone (GH), insulin, thyroxine (T4), triiodothyronine (T3), cortisol and glucagon concentrations were measured in plasma of fasted pigs. Concentrations of carcass lipid, dry matter and ash were higher in newborn Ossabaw pigs than in newborn Yorkshire pigs. Survival through 72 hr of fasting was lower among Yorkshire pigs. Yorkshire and Ossabaw pigs had similar concentrations of metabolites and hormones at birth, with the exceptions of lower plasma GH and higher T3 concentrations in Ossabaw pigs. Higher plasma T3 concentrations would indicate a greater potential for fatty acid oxidation. During fasting, Ossabaw pigs had lower plasma GH and T4 concentrations and higher glucagon and FFA concentrations. Increased survival among newborn Ossabaw pigs may have been due to increased availability of FFA during fasting, and to a greater potential for gluconeogenesis through increased oxidation of fatty acids and higher plasma glucagon concentrations. This would suggest that maternal treatments that would increase storage of fat and(or) increase the capacity for oxidation of fat in utero would improve survival of newborn pigs.

  9. Investigation of serum thyroxine in obstructive sleep apnea-hypopnea syndrome patients%阻塞性睡眠呼吸暂停低通气综合征患者血清甲状腺素的研究

    Institute of Scientific and Technical Information of China (English)

    何志红; 郭丽萍; 吴雅丽; 段争; 高英; 彭少舫; 吴颂时; 张敏


    Objective To investigate the changes of serum thyroxine level in obstructive sleep apnea-hy-popnea syndrome(OSAHS) patients and to assess the role of serum thyroxine in the development of OSAHS. Meth-ods Polysomnography was used to examine the patients with OSAHS and fasting plasma serum thyroxine level were higher in obese OSAHS patients than in obese controls[ (43.56±3.48)cm vs (38.33±3.08)cm,t =4. 258,P < 0.05 ], in non-obese OSAHS patients than in non-obese control group [ (40.50±1.05 )cm vs (36.17±3.13 )cm, t = 3. 146 ,P < 0.05 ] . The levels of FT3 was (6.35±3.15 ) pmol/L in obese OSAHS patients and ( 4.08±2.37 ) pmol/L in control subjects ( t = 2.203 ,P < 0.05 ). That was ( 3.42±0.57 ) pmol/L in non-obese OSAHS patients related with AHI and microarousal index (r = 0. 500, P < 0.05;r = 0.561, P < 0.05 ), and FT4 was also positively with neck circumference( t = 0.489, P < 0.05 ), TSH level was negatively correlated with neck circumference ( t = - 0.500, P < 0.05 ) and was positively correlated with the percentage of body fat ( r = 0.498, P < 0.05 ). Conclu-sions The FT3 levels are significantly higher in the OSAHS patients than that in control subjects, though all FT3 lev-els are normal, suggesting that there are possibility to have abnormal metabolism. At the same time, FT3 level is posi-tively correlated with neck circumference ,suggesting that the OSAHS patients' higher neck circumference is correla-ted with thyroxine.%目的 探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血清甲状腺素水平以及在OSAHS病情进展中的作用.方法 选择OSAHS患者和健康者(对照组)各40例,均为男性,分别行多导睡眠图检查,并测定空腹甲状腺素水平.结果 ①OSAHS肥胖组的颈围为(43.56±3.48)cm,对照肥胖组为(38.33±3.08)cm,2组比较差异有统计学意义(t=4.258,P<0.05);OSAHS非肥胖组的颈围为(40.50±1.05)cm,对照非肥胖组为(36.17±3.13)cm,2组比较差异有统计学意义(t=3.146,P<0

  10. Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. (United States)

    Rasmussen, D D; Boldt, B M; Wilkinson, C W; Yellon, S M; Matsumoto, A M


    Human and rat pineal melatonin secretion decline with aging, whereas visceral fat and plasma insulin levels increase. Melatonin modulates fat metabolism in some mammalian species, so these aging-associated melatonin, fat and insulin changes could be functionally related. Accordingly, we investigated the effects of daily melatonin supplementation to male Sprague-Dawley rats, starting at middle age (10 months) and continuing into old age (22 months). Melatonin was added to the drinking water (92% of which was consumed at night) at a dosage (4 microg/ml) previously reported to attenuate the aging-associated decrease in survival rate in male rats, as well as at a 10-fold lower dosage. The higher dosage produced nocturnal plasma melatonin levels in middle-aged rats which were 15-fold higher than in young (4 months) rats; nocturnal plasma melatonin levels in middle-aged rats receiving the lower dosage were not significantly different from young or middle-aged controls. Relative (% of body wt) retroperitoneal and epididymal fat, as well as plasma insulin and leptin levels, were all significantly increased at middle age when compared to young rats. All were restored within 10 weeks to youthful (4 month) levels in response to both dosages of melatonin. Continued treatment until old age maintained suppression of visceral (retroperitoneal + epididymal) fat levels. Plasma corticosterone and total thyroxine (T4) levels were not significantly altered by aging or melatonin treatment. Plasma testosterone, insulin-like growth factor I (IGF-I) and total triiodothyronine (T3) decreased by middle age; these aging-associated decreases were not significantly altered by melatonin treatment. Thus, visceral fat, insulin and leptin responses to melatonin administration may be independent of marked changes in gonadal, thyroid, adrenal or somatotropin regulation. Since increased visceral fat is associated with increased insulin resistance, diabetes, and cardiovascular disease, these results

  11. Reduction of Thyroxine and Related Compounds on Silver. (United States)


    cathodic stripping . Stripping voltammetry in d flow system is feasible and sensitive, has been employed by Wang L17,18] and others [19] in flow injection...oxidation peak and cathodic stripping peak due to the presence of iodide ions in the region of the electrode as a product of the reduction of T4 is seen...oxidation, chemical or electrochemical, to iodine with spectroscopic detection, and (d) stripping voltammetry of iodide on a silver electrode. For liquid

  12. Partial characterization of Acanthamoeba castellanii (T4 genotype) DNase activity. (United States)

    Iqbal, Junaid; Panjwani, Shamvil; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed


    The deoxyribonuclease (DNase) activities of Acanthamoeba castellanii belonging to the T4 genotype were investigated. Using zymographic assays, the DNase activities had approximate molecular masses of 25 and 35 kDa. A. castellanii DNases exhibited activity at wide-ranging temperature of up to 60 °C and at pH ranging from 4 to 9. The DNases activities were unaffected by proteinase-K treatment, divalent cations such as Ca(++), Cu(++), Mg(++), and Zn(++), or divalent cation chelating agent ethylenediaminetetraacetic acid (EDTA) or sodium dodecyl sulfate (SDS). The non-reliance on divalent cations and homology data suggests that A. castellanii DNases belong to the class of eukaryotic lysosomal DNase II but exhibit robust properties. The DNases activity in A. castellanii interfered with the genomic DNA extraction. Extraction methods involving EDTA, SDS, and proteinase-K resulted in low yield of genomic DNA. On the other hand, these methods resulted in high yield of genomic DNA from human cells suggesting the robust nature of A. castellanii DNases that are unaffected by reagents normally used in blocking eukaryotic DNases. In contrast, the use of chaotropic agent such as guanidine thiocyanate improved the yield of genomic DNA from A. castellanii cells significantly. Further purification and characterization of Acanthamoeba DNases is needed to study their non-classic distinct properties and to determine their role in the biology, cellular differentiation, cell cycle progression, and arrest of Acanthamoeba.

  13. A promiscuous DNA packaging machine from bacteriophage T4.

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    Zhihong Zhang

    Full Text Available Complex viruses are assembled from simple protein subunits by sequential and irreversible assembly. During genome packaging in bacteriophages, a powerful molecular motor assembles at the special portal vertex of an empty prohead to initiate packaging. The capsid expands after about 10%-25% of the genome is packaged. When the head is full, the motor cuts the concatemeric DNA and dissociates from the head. Conformational changes, particularly in the portal, are thought to drive these sequential transitions. We found that the phage T4 packaging machine is highly promiscuous, translocating DNA into finished phage heads as well as into proheads. Optical tweezers experiments show that single motors can force exogenous DNA into phage heads at the same rate as into proheads. Single molecule fluorescence measurements demonstrate that phage heads undergo repeated initiations, packaging multiple DNA molecules into the same head. These results suggest that the phage DNA packaging machine has unusual conformational plasticity, powering DNA into an apparently passive capsid receptacle, including the highly stable virus shell, until it is full. These features probably led to the evolution of viral genomes that fit capsid volume, a strikingly common phenomenon in double-stranded DNA viruses, and will potentially allow design of a novel class of nanocapsid delivery vehicles.

  14. Pediatric Reference Intervals for Free Thyroxine and Free Triiodothyronine by Equilibrium Dialysis-Liquid Chromatography-Tandem Mass Spectrometry (United States)

    La’ulu, Sonia L.; Rasmussen, Kyle J.; Straseski, Joely A.


    Objective: Thyroid hormone concentrations fluctuate during growth and development. To accurately diagnose thyroid disease in pediatric patients, reference intervals (RIs) should be established with appropriate age groups from an adequate number of healthy subjects using the most exact methods possible. Obtaining statistically useful numbers of healthy patients is particularly challenging for pediatric populations. The objective of this study was to determine non-parametric RIs for free thyroxine (fT4) and free triiodothyronine (fT3) using equilibrium dialysis-high performance liquid chromatography-tandem mass spectrometry with over 2200 healthy children 6 months-17 years of age. Methods: Subjects were negative for both thyroglobulin and thyroid peroxidase autoantibodies and had normal thyrotropin concentrations. The study included 2213 children (1129 boys and 1084 girls), with at least 120 subjects (average of 125) from each year of life, except for the 6 month to 1 year age group (n=96). Results: Non-parametric RIs (95th percentile) for fT4 were: 18.0-34.7 pmol/L (boys and girls, 6 months-6 years) and 14.2-25.7 pmol/L (boys and girls, 7-17 years). RIs for fT3 were: 5.8-13.1 pmol/L (girls, 6 months-6 years); 5.7-11.8 pmol/L (boys, 6 months-6 years); 5.7-10.0 pmol/L (boys and girls, 7-12 years); 4.5-8.6 pmol/L (girls, 13-17 years); and 5.2-9.4 pmol/L (boys, 13-17 years). Conclusion: Numerous significant differences were observed between pediatric age groups and previously established adult ranges. This emphasizes the need for well-characterized RIs for thyroid hormones in the pediatric population. PMID:26758817

  15. Pediatric Reference Intervals for Free Thyroxine and Free Triiodothyronine by Equilibrium Dialysis-Liquid Chromatography-Tandem Mass Spectrometry. (United States)

    La'ulu, Sonia L; Rasmussen, Kyle J; Straseski, Joely A


    Thyroid hormone concentrations fluctuate during growth and development. To accurately diagnose thyroid disease in pediatric patients, reference intervals (RIs) should be established with appropriate age groups from an adequate number of healthy subjects using the most exact methods possible. Obtaining statistically useful numbers of healthy patients is particularly challenging for pediatric populations. The objective of this study was to determine non-parametric RIs for free thyroxine (fT4) and free triiodothyronine (fT3) using equilibrium dialysis-high performance liquid chromatography-tandem mass spectrometry with over 2200 healthy children 6 months-17 years of age. Subjects were negative for both thyroglobulin and thyroid peroxidase autoantibodies and had normal thyrotropin concentrations. The study included 2213 children (1129 boys and 1084 girls), with at least 120 subjects (average of 125) from each year of life, except for the 6 month to 1 year age group (n=96). Non-parametric RIs (95th percentile) for fT4 were: 18.0-34.7 pmol/L (boys and girls, 6 months-6 years) and 14.2-25.7 pmol/L (boys and girls, 7-17 years). RIs for fT3 were: 5.8-13.1 pmol/L (girls, 6 months-6 years); 5.7-11.8 pmol/L (boys, 6 months-6 years); 5.7-10.0 pmol/L (boys and girls, 7-12 years); 4.5-8.6 pmol/L (girls, 13-17 years); and 5.2-9.4 pmol/L (boys, 13-17 years). Numerous significant differences were observed between pediatric age groups and previously established adult ranges. This emphasizes the need for well-characterized RIs for thyroid hormones in the pediatric population.

  16. Quantification of thyroxine and 3,5,3'-triiodo-thyronine in human and animal hearts by a novel liquid chromatography-tandem mass spectrometry method. (United States)

    Saba, A; Donzelli, R; Colligiani, D; Raffaelli, A; Nannipieri, M; Kusmic, C; Dos Remedios, C G; Simonides, W S; Iervasi, G; Zucchi, R


    Assaying tissue T3 and T4 would provide important information in experimental and clinical investigations. A novel method to determine tissue T3 and T4 by HPLC coupled to mass spectrometry is described. The major difference vs. previously described methods lies in the addition of a derivatization step, that is, to convert T3 and T4 into the corresponding butyl esters. The yield of esterification was ̴ 100% for T3 and 80% for T4. The assay was linear (r>0.99) in the range of 0.2-50 ng/ml, accuracy was in the order of 70-75%, and the minimum tissue amount needed was in the order of 50 mg, that is, about one order of magnitude lower than observed with the same equipment (AB Sciex API 4000 triple quadrupole mass spectrometer) if derivatization was omitted. The method allowed detection of T3 and T4 in human left ventricle biopsies yielding concentrations of 1.51±0.16 and 5.94±0.63 pmol/g, respectively. In rats treated with different dosages of exogenous T3 or T4, good correlations (r>0.90) between plasma and myocardial T3 and T4 concentrations were observed, although in specific subsets different plasma T4 concentrations were not associated with different tissue content in T4. We conclude that this method could provide a novel insight into the relationship between plasma and tissue thyroid hormone levels. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Effects of thyroxine on metamorphosis of orange-spotted grouper (Epinephelus coioides) larvae%甲状腺素对斜带石斑鱼仔鱼变态的影响

    Institute of Scientific and Technical Information of China (English)

    唐啸尘; 刘晓春; 林浩然; 张海发; 刘付永忠


    用甲状腺素(Thyroxine,T4)处理斜带石斑鱼Epinephelus coioides仔鱼,研究T4对仔鱼变态的影响.仔鱼在变态前期和变态高峰期,用0.01mg·L-1T4处理7d后仔鱼完成变态,用0.10mg·L-1T4处理4d后仔鱼完成变态,用1.00mg·L-1T4处理3d后仔鱼完成变态,对照组仔鱼在实验期间未能完成变态.用0.01mg·L-1T4处理变态高峰期仔鱼其存活率明显提高和全长增长明显变慢,但对变态前期仔鱼无影响;用0.10和1.00mg·L-1T4处理变态前期和变态高峰期仔鱼,其存活率显著降低和全长增长明显变慢.结果表明,在变态高峰期用0.01mg·L-1T4处理仔鱼能加速它的变态并提高其存活率.

  18. T4噬菌体的组装、感染及细胞裂解%Assembly, Infection and Cell Lysis of Bacteriophage T4

    Institute of Scientific and Technical Information of China (English)

    颜晨; 逯凯; 任慧英


    To further develop and utilize T4 phage display and phage therapy, and open the broader prospect for the progress in study of T4 phage, the important components of T4 phage particles was analyzed by molecular biology techniques, such as the head, the tail and the basement. The protein composition of these structure were confirmed. DNA packing which was an important part in the assembly of T4 phage particle was described in detail. Not only the phenomenon of infection and lysis, but also the superinfection exclusion and lysis inhibition in T4 life cycles introduced with molecular mechanism and impact factor. The assembly and infection mechanism of T4 phage would be known much better by these research.%为深入开发利用T4噬菌体展示系统及T4噬菌体的临床细菌病治疗,应用现代各种分子生物学手段,在蛋白分子和组成结构上对T4噬菌体颗粒的各个重要组成部分进行分析,例如头部、尾部和尾板,描述了其蛋白构成和各种影响因子,并着重介绍了在噬菌体装配中最为重要的DNA的包装.同时针对噬菌体T4的感染与超感染免疫性和感染所导致的细胞裂解和裂解抑制等方面,介绍了这些现象发生的分子机制和影响因素.以期对T4噬菌体的分子装配和侵染机制有更为深刻的了解.

  19. Pregnant women on thyroxine substitution are often dysregulated in early pregnancy. (United States)

    Hallengren, Bengt; Lantz, Mikael; Andreasson, Bengt; Grennert, Lars


    Thyroid hormones are important for normal fetal development. Maternal hypothyroidism during early pregnancy is associated with impaired neuropsychological development of children and other adverse outcomes. The primary aim of this prospective study was to determine whether thyroxine-treated pregnant women with hypothyroidism are adequately thyroxine substituted in early pregnancy. A secondary aim was to determine if fetal loss differed between females with thyrotropin (TSH) values within and outside the reference range at their first TSH test, scheduled for 1-2 weeks after verification of pregnancy. This was a prospective open-labeled study. During the years 1997-2002, 119 consecutive pregnancies in 101 females with thyroid diseases were followed at the Department of Endocrinology, Malmö University Hospital. At the first visit, 63 patients, median age 30 years (range 17-45 years), were on thyroxine substitution therapy for hypothyroidism. In these patients 83% were in their first trimester at the time of the initial test. Of the 63 patients on thyroxine substitution for hypothyroidism 32 (51%; Group A) patients had serum TSH values within the reference range at their initial test and 31 (49%; Group B) had serum TSH values outside the reference range. Twelve (19%) had TSH values of 4.0 mIU=l. The fetal loss was 2 of 32 (6%) in Group A compared to 9 of 31 (29%) in Group B ( p pregnant women on thyroxine substitution, serum TSH values were outside the reference range when first tested, generally in the first trimester. Fetal loss was significantly greater in pregnant women with abnormal TSH values compared to those with normal TSH values. Thyroid function in pregnant women on thyroxine substitution should be monitored early in pregnancy and carefully followed during pregnancy. The thyroxine dose should be increased as needed early in pregnancy to avoid hypothyroidism.

  20. Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75 μg. (United States)

    Penin, Manuel; Trigo, Cristina; López, Yolanda; Barragáns, María


    Treatment of hypothyroid pregnant women is usually calculated based on weight (1 μg/kg/day) and TSH levels. This study assessed the usefulness of treating these women with a fixed dose of 75 μg/day. All women with pregnancy diagnosed from January to August 2012 in the Vigo Health Area (Spain) without previous diagnosis of thyroid disease or thyroxine treatment and with TSH levels over 4,5 mUI/ml were enrolled by consecutive sampling. All 116 women in the sample were treated with a fixed daily dose of thyroxine 75 μg-thyroxine levels were measured at two, four, and six months, and thyroxine dose was modified if TSH level was lower than 0.3 or higher than 4.5 mUI/ml. A woman had a TSH level less than 0.3 mUI/ml in a test; reduction of thyroxine dose to 50 μg/day allowed for maintaining TSH level within the desired range until delivery. Six women had TSH levels over 4.5 mUI/ml in one test; in all of them, increase in thyroxine dose to 100 μg/day allowed for maintaining the level within the desired range until delivery. Fixed daily doses of thyroxine 75 μg allowed for achieving goal TSH levels in most of our pregnant women with subclinical hypothyroidism, irrespective of their weight and baseline TSH level. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  1. Sequential defunctionalization followed by thyroxine supple-mentation as preoperative preparation of hyperthyroid patients undergoing thyroidectomy

    Institute of Scientific and Technical Information of China (English)

    ZHU Jing-qiang; WU Xiao-ying; LI Zhi-hui; GONG Ri-xiang; WEI Tao; ZHANG Heng; ZHANG Wen-yan; YANG Xiao-yan; LUO Yan-li; GONG Shu


    Background Preparing hyperthyroid patients for thyroid surgery with a combination of antithyroid drugs and thyroxine has long been controversial because this combination usually results in only partial inhibition of thyroid function. We therefore used large doses of antithyroid drugs to completely inhibit the synthesis of thyroxine and render the thyroid gland defunctionalized. We then administered physiologic doses of thyroxine to inhibit thyroid-stimulating hormone secretion. We have named this treatment "sequential thyroid defunctionalization followed by thyroxine supplementation." Methods Four hundred and seventy-one hyperthyroid patients seen at our hospital were divided into experimental and control groups. The control group was treated preoperatively with antithyroid drugs and iodine preparation. The experimental group was further divided into four subgroups and treated with "sequential thyroid defunctionalization followed by thyroxine supplementation". Each of the four subgroups received different doses of antithyroid drugs and thyroxine for differing time periods. Thyroid function was assessed at each stage of treatment, as were operative blood loss volumes and postoperative complications.Results Compared to the control group, the four experimental groups showed less thyroid congestion and surface varices at surgery. Patients in subgroup A also had thyroid glands that were almost histologically normal. The mean operative blood loss volume of the experimental group was less than that of the control group((326±1 63)mlin the control group;(196±57)ml in subgroup A:(230±71)ml in subgroup B;(240±80)ml in subgroup C;and(31 2±97)ml in subgroup D).The postoperative complication rate of the experimental group was 8.64%(21/243)whereas that of the control group was 1 7.54%(40/228).Conclusions Sequential thyroid defunctionalization followed by thyroxine supplementation is effective in reducing the bleeding volume and postoperative complication rate in selected

  2. 甲状腺素对斜带石斑鱼卵黄囊期仔鱼生长发育的影响%Effect of Thyroxine on Growth and Development of Epinephelus coioides Yolk-sac Larvae

    Institute of Scientific and Technical Information of China (English)

    唐啸尘; 周歧存; 丁燏; 张海发; 王云新


    用4种不同浓度的甲状腺素(T4)分别浸泡斜带石斑鱼卵黄囊期仔鱼,研究T4对仔鱼发育、生长和存活的影响.结果表明,在孵化后24h内,T4对仔鱼发育的促进作用不明显;在孵化24h后,T4对仔鱼消化道的发育有促进作用.在孵化后72h,0.01 mg·L-1 T4处理组仔鱼小肠管径、直肠管径、全长与对照组相比差异均不明显;0.10 mg·L-1和1.00 mg·L-1 T4处理组仔鱼小肠和直肠管径显著比对照组大(P<0.01),1.00mg·L-1 T4处理组仔鱼全长显著比对照组短(P<0.01),而0.10 mg·L-1处理组仔鱼全长与对照组相比无明显差异(P>0.05).在孵化后第8天,0.10 mg·L-1 T4处理组仔鱼存活率明显比对照组高(P<0.01),而0.01 mg·L-1 T4组和1.00mg·L-l T4组与对照组之间存活率差异不明显(P>0.05).结果提示0.10mg.L-1 T4处理能促进斜带石斑鱼卵黄囊期仔鱼的消化道发育并提高其存活率.%The effect of four doses of thyroxine (T4) on orange-spotted grouper (Epinephelus coioides)yolk-sac larvae was studied. The effect of T4 on larval development was not obvious within 24 hourspost-hatching (hph). However, the advancement in development of gut was induced by T4 treatmentafter 24 hph. The differences between the control and 0.01 mg · L-1 T4 groups were not observed at 72hph. Compared with the control, the diameter of larval intestine and rectum in both 0.10 mg · L-1 and1.00 mg · L-1 T4 groups were obviously longer at 72 hph(P < 0.01), however, the larval total length in1.00 mg · L-1 T4 groups was obviously shorter(P < 0.01), while the larval total length were notsignificantly affected by 0.10 mg · L-1 T4 treatment(P > 0.05). The rate of survival in 0.10 mg · L-1 T4groups was obviously higher than that in the control by 8 days post-hatching(P < 0.01), while that ineither 0.01 mg · L-1 groups or 1.00 mg · L-1 T4 groups was not(P > 0.05). The results indicated that 0.10mg · L-1 T4 treatment could

  3. Development of reagents for radioimmunoassay of: triiodothyronine, thyroxine and thyrotrophin; Desarrollo de reactivos para el radioinmunoanalisis de: triyodotironina, tiroxina y tirotrofina

    Energy Technology Data Exchange (ETDEWEB)

    Delgado S, B.; Lavalley E, C.; Ruiz J, A.; Garcia F, C.; Zamorano A, F


    The radioimmunoassay (RIA) of thyroid hormones it is the but it frequents of all the studies carried out by RIA in the laboratories of Nuclear Medicine, these essays are carried out with imported reagents. In the ININ the reagents and the necessary methodology have been developed for the triiodothyronine (T3), thyroxine (T4) and thyrotrophin (TSH). The good titles of the antibodies (Ac) primary for each hormone were of 1:4,000; 1:750 and 1:1,500. The used separation system was of double Ac with PEG to 10%, with titles of 1:10 for the second Ac of lamb. The specific activity for 125-I-T3 and 125-I-T4 oscillate between 850 at 900 {mu}Ci / {mu} g: being this of 90 {mu} Ci /{mu}g for TSH. To the first two hormones they were added 1-8 aniline naftalen sulfonic acid (ANS) to concentrations of 3 and 2 mg/ml respectively. As buffer for T3 and T4 it was used Tris-HCl pH 8.6 and PBS with normal serum of rabbit (SNC) for TSH. The standards got ready in buffer or free serum of thyroid hormones. The slope of the standard curves varied between -2.3 to -2.7 and the variation intra and inter assay among 4 to 10%. It is had at the moment in the ININ with standardized reagents for the RIA of T3, T4 and TSH, it is hoped to carry out tests in other laboratories and to establish the conditions of stability more appropriate to begin the preparation of pilot reagents. (Author)

  4. 子代T4的PCR和real time PCR测定%Quantification of progeny T4 by PCR and real-time PCR

    Institute of Scientific and Technical Information of China (English)

    刘邻渭; 杨公明


    目的:为建立通过测定转换样品T4而检验样品大肠杆菌的新方法,探讨快速测定转换样品中T4的PCR技术.方法:以T4DNA纯化样品水稀释液和转换样品沸水浴处理产物分别为模板样液,经过两对引物PCR及real time PCR的试用和比较,优选定量检测转换样品中T4的适宜方法和条件.结果:源自T4 ligase的一对引物具有较高的灵敏度和特异性;针对纯化T4DNA配制的模板样液,优化的PCR和real time PCR至少可分别精确检出39.25和3.925 pg/ml的T4DNA;针对沸水浴处理转换样品制备的模板样液,PCR和real time PCR可清楚区别不同浓度的转换样品,PCR的检出极限为500 PFU/ml T4的转换样品,real time PCR的检测极限为35 PFU/ml T4的转换样品.结论:采用PCR和real time PCR可快速定量测定转换样品中的T4含量,real time PCR比PCR的灵敏度高约一个数量级.

  5. Pre-β-HDL formation relates to high-normal free thyroxine in type 2 diabetes mellitus. (United States)

    van Tienhoven-Wind, Lynnda J N; Perton, Frank G; Dullaart, Robin P F


    Low-normal thyroid function within the euthyroid range may influence plasma lipoprotein levels. Associations between variation in thyroid function and pre-β-high density lipoproteins (pre-β-HDL), i.e. lipid-poor or lipid free HDL particles that act as initial acceptor of cell-derived cholesterol, are unknown. We determined relationships of plasma pre-β-HDL with thyroid function in euthyroid subjects with and without type 2 diabetes mellitus (T2DM). TSH, free T4, plasma (apo)lipoproteins, pre-β-HDL, pre-β-HDL formation (pre-β-HDL generation during incubation with lecithin:cholesterol acyltransferase being inhibited) and phospholipid transfer protein (PLTP) activity were measured in fasting plasma from 72 T2DM and 82 non-diabetic subjects. TSH was similar and free T4 was slightly higher (P diabetic subjects. HDL cholesterol and apoA-I were lower, whereas pre-β-HDL (expressed as % of apoA-I), triglycerides and PLTP activity were higher in T2DM (P HDL formation (in apoA-I concentration and in % of apoA-I) was positively related to free T4, PLTP activity, total cholesterol and triglycerides (P HDL formation was positively related to free T4 (in apoA-I concentration: β = 0.278, P = 0.014; in % of apoA-I: β = 0.343, P = 0.003) in T2DM, but not in non-diabetic subjects (both P > 0.30; interaction terms: both P HDL in T2DM.

  6. Potential of l-thyroxine to differentiate osteoblast-like cells via Angiopoietin1. (United States)

    Park, See-Hyoung; Lee, Jongsung; Kang, Mi-Ae; Moon, Young Jae; Wang, Sung Il; Kim, Kyoung Min; Park, Byung-Hyun; Jang, Kyu Yun; Kim, Jung Ryul


    Angiogenesis is closely associated with osteoblast differentiation. Previously, we demonstrated that bone formation can be accelerated by treatment with COMP-Angiopoietin1, a known angiogenic factor. Angiopoietin1 (Ang1) is a specific growth factor that generates stable and mature vasculature through the Tie2 receptor. In this study, we aimed to identify a novel drug that can activate endogenous Ang1 expression as a pharmacological treatment for bone formation. Therefore, Ang1 expression was examined in U2OS osteoblast-like cells treated with 770 drugs from a library of Food and Drug Administration (FDA)-approved drugs by using ELISA for Ang1. l-thyroxine was selected as a novel drug candidate. l-Thyroxine is a synthetic form of the hormone thyroxine, which is used to treat patients with hypothyroidism. Enzyme-linked immunosorbent assays (ELISAs) were performed to test whether Ang1 is induced in a dose-dependent manner in human osteoblast-like cell lines, U2OS and MG63. The effects of l-thyroxine on osteoblast differentiation and mineralization were evaluated by alkaline phosphatase (ALP) activity and Alizarin red s staining. To determine the molecular mechanism, the expression of proteins related to bone formation and differentiation, such as type I collagen (COL1A1), osteocalcin (OC), bone sialoprotein (BSP), distal-less homeobox 5 (Dlx5), Runt-related transcription factor 2 (Runx2), osterix (OSX), and ALP, was tested by Western blotting analysis. Consequently, l-thyroxine induced Ang1 expression in a dose-dependent manner in both U2OS and M63 cells, which was confirmed by ELISA and Western blotting. Also, l-thyroxine activated ALP activity in U2OS and MG63 cells as well as ALP expression. Furthermore, l-thyroxine enhanced the expression of COL1A1, Runx2, OC, BSP, Dlx5, and OSX mRNA and proteins. Taken together, we demonstrated that l-thyroxine increased Ang1 expression and induces bone formation, differentiation, and mineralization in U2OS and MG63 cell lines

  7. Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. (United States)

    Schneider, M J; Fiering, S N; Pallud, S E; Parlow, A F; St Germain, D L; Galton, V A


    The type 2 deiodinase (D2), a selenoenzyme that catalyzes the conversion of T4 to T3 via 5'-deiodination, is expressed in the pituitary, brain, brown adipose tissue (BAT), and the reproductive tract. To examine the physiological role of this enzyme, a mouse strain lacking D2 activity was developed using homologous recombination. The targeting vector contained the Neo gene in place of a 2.6-kb segment of the Dio2 gene. This segment comprises 72% of the coding region and includes the TGA codon that codes for the selenocysteine located at the active site of the enzyme. Mice homologous for the targeted deletion [D2 knockout (D2KO)] had no gross phenotypic abnormalities, and development and reproductive function appeared normal, except for mild growth retardation (9%) in males. No D2 activity was observed in any tissue in D2KO mice under basal conditions, or under those that normally induce this enzyme such as cold-exposure (BAT) or hypothyroidism (brain, BAT, and pituitary gland). Furthermore, no D2 activity was present in cultured astrocytes, nor could it be induced by treatment of the cells with forskolin. Although D2 mRNA transcripts were detected in BAT RNA obtained from cold-exposed wild-type (WT) mice, none was detected in BAT RNA from comparably-treated D2KO mice. Levels of D1 in the liver, thyroid, and pituitary were the same in WT and D2KO animals, whereas D3 activity in D2KO cerebrum was twice that in WT cerebrum. Serum T3 levels were comparable in adult WT and D2KO mice. However, serum T4 and TSH levels were both elevated significantly (40% and 100%, respectively) in the D2KO mice, suggesting that the pituitary gland of the D2KO mouse is resistant to the feedback effect of plasma T4. This view was substantiated by the finding that serum TSH levels in hypothyroid WT mice were suppressed by administration of either T4 or T3, but only T3 was effective in the D2KO mouse. The data also suggest that the clearance of T4 from plasma was reduced in the D2KO mouse. In

  8. Normal cortisol response to cold pressor test, but lower free thyroxine, after recovery from undernutrition. (United States)

    Martins, Vinicius J B; Neves, Andrea P O; Garcia, Márcia C; Spadari, Regina C; Clemente, Ana Paula G; de Albuquerque, Maria P; Hoffman, Daniel J; Sawaya, Ana L


    Undernutrition is a stressor with long-term consequences, and the effect of nutritional recovery on cortisol and thyroid hormone status is unknown. To investigate basal thyroid hormones and the cortisol response to a cold pressor test in children recovered from undernutrition, a cross-sectional study was undertaken on children (6-16 years) separated into four groups: control (n 41), stunted (n 31), underweight (n 27) and recovered (n 31). Salivary cortisol was collected over the course of 10 h: upon awakening, before and after an unpleasant and a pleasant stimulus. Cortisol upon awakening was highest in the stunted and lowest in the underweight groups: control=5·05 (95% CI 3·71, 6·89) nmol/l, stunted=6·62 (95% CI 3·97, 11·02) nmol/l, underweight=2·51 (95% CI 1·75, 3·63) nmol/l and recovered=3·46 (95% CI 2·46, 4·90) nmol/l (P=0·005). Girls had higher cortisol concentrations upon awakening compared with boys (P=0·021). The undernourished groups showed an elevated cortisol response both to the unpleasant stimulus and at the last measurement (16.00 hours) compared with that of the recovered group: AUC, control=2·07 (95% CI 1·69, 2·45) nmol/l×30 min, stunted=2·48 (95% CI 1·91, 3·06) nmol/l×30 min, underweight=2·52 (95% CI 2·07, 2·97) nmol/l×30 min, recovered=1·68 (95% CI 1·26, 2·11) nmol/l×30 min (P=0·042); and control=2·03 (95% CI 1·75, 2·39) nmol/l×30 min, stunted=2·51 (95% CI 1·97, 3·19) nmol/l×30 min, underweight=2·61 (95% CI 2·16, 3·16) nmol/l×30 min, recovered=1·70 (95% CI 1·42, 2·03) nmol/l×30 min (P=0·009). Lower free thyroxine (T4) was found in the recovered and stunted groups: control=1·28 (95% CI 1·18, 1·39) pmol/l, stunted=0·98 (95% CI 0·87, 1·10) pmol/l, underweight=1·10 (95% CI 1·01, 1·21) pmol/l and recovered=0·90 (95% CI 0·83, 0·99) pmol/l (Pcortisol concentration along 10 h (06.00-16.00 hours) in the recovered compared with the other groups (P=0·017), and similar concentrations between the

  9. Effects of 5,5'-diphenylhydantoin on thyroxine and 3,5,3'-triiodothyronine concentrations in several tissues of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder-van der Elst, J.Pv.; van der Heide, D. (University Hospital, Leiden (Netherlands))


    We studied the effect of 5,5'-diphenylhydantoin (phenytoin, DPH) on the metabolism of thyroid hormones, the intracellular concentration of T4, and the source and concentration of T3. Two groups of six male Wistar rats received a continuous infusion of 10 ml saline/rat. day. One group received DPH in their food (50 mg/kg BW) for 20 days. For both groups (125I)T4 and (131I)T3 were added to the infusion fluid for the last 10 and 7 days, respectively. At isotopic equilibrium the rats were bled and perfused. Compared to the controls, plasma T4 and T3 in the DPH group were reduced (22% and 31%, respectively); TSH did not change. The rate of production of T4 and the plasma appearance rate for T3 were decreased. Thyroidal T3 production was markedly reduced. From the increased (125I)T3/(125I)T4 ratio for plasma, it follows that total body conversion was enhanced. The tissue T4 concentrations decreased in parallel with the plasma T4 level. Total T3 was reduced in all organs. In tissues in which local conversion does not occur, i.e. heart and muscle, the decrease reflected the decrease in plasma T3. In the liver both plasma-derived T3 and locally produced T3 were diminished. In cerebellum and brain the plasma-derived T3 pool was even smaller than was expected from the decrease in plasma T3. This was partly compensated by an increase in local conversion. Only for these two organs was the decrease in the tissue/plasma ratio for (131I)T3 significant. Our results suggest tissue hypothyroidism, caused by a decrease in the production of T4 and T3, which is partly compensated by increased conversion in several organs. The transport of T3 into cerebellum and brain is disturbed, which can be attributed to the mode of action of DPH.

  10. The effect of thyroxin on hepatic redox equilibrium and lipid metabolism in rats treated with doxorubicin

    Directory of Open Access Journals (Sweden)

    Czuba Bartosz


    Full Text Available The main side effects of the administration of doxorubicin, a widely used anticancer drug, is the generation of a reactive oxygen species (ROS in normal cells. As a result, redox disorders and secondary oxidative stress are developed. Doxorubicin ROS generation is attributed to enzymes that are produced abundantly in hepatocytes. Oxidative stress has been a well-known risk factor of doxorubicin-related toxicity. However, in addition, according to the data collected in the last decade, changes in thyroxin status can propagate ROS generation, and, thus, initiate the doxorubicin hepatic effect. Moreover, both compounds have an impact on the cell metabolism. The aim of the study was to verify the thesis that thyroxin can modulate the effect of doxorubicin with regard to redox status and lipid metabolism disorders. In our work, we determined the ratio of NADP+/ NADPH and NAD+/NADH in liver homogenates, blood ketone bodies and triglycerides in the liver and blood in rats treated with doxorubicin and thyroxin. Our results indicate that thyroxin has an insignificant effect on NAD+/NADH, NADP+/NADPH ratios and on hepatic and blood triglycerides. Moreover, thyroxin administration normalized the level of blood ketone bodies that was disturbed by doxorubicin.

  11. Age-Dependent Variation in Hormonal Concentration and Biochemical Constituents in Blood Plasma of Indian Native Fowl

    Directory of Open Access Journals (Sweden)

    Avishek Biswas


    Full Text Available This experiment was to investigate the age-related changes in hormonal concentration and biochemical constituents of blood plasma in Indian native desi fowl. One hundred and sixty two (54 from each breed, i.e., Kadaknath (KN, Aseel peela (AP, and White leghorn (WLH day-old female chicks were randomly divided into nine groups each of 18 chicks (3 groups × 3 replicates. WLH was taken in this study to compare the characteristics of Indian native desi fowl. The highest level of estrogen hormone in WLH and desi fowl in blood plasma was occurred at 18 and 24 wks of age, respectively. Whereas, the peak of progesterone hormone in WLH hens noticed around 24 wks, in case of desi fowls, it was at 30 wks of age. Irrespective of the breed, the hormonal profile of Triiodothyronine (T3 and Thyroxine (T4 in blood plasma was found highest around 6 to 12 wks of age. Activities of acid phosphatase (ACP increased with the reduction of alkaline phosphate (ALP activities at different time intervals. Irrespective of the breed, transaminases (glutamic oxaloacetic transaminase (GOT and glutamic pyruvic transaminase (GPT activities of blood plasma increased linearly with the advancement of the age. From this study, it may be concluded that sexual maturity of the Indian native desi fowl occurred nearly 6 wk later (24 wk than WLH.

  12. Plasma thyroid hormones and corticosterone levels in blood of chicken embryos and post hatch chickens exposed during incubation to 1800 MHz electromagnetic field

    Directory of Open Access Journals (Sweden)

    Krzysztof Pawlak


    Full Text Available Introduction: This study attempted to determine the effect of a 1800 MHz electromagnetic field (EMF (only carrier frequency on thyroxine (T4, triiodothyronine (T3 and corticosterone (CORT concentrations in the blood plasma of chick embryos, and to investigate the effect of electromagnetic field (EMF exposure during embryogenesis on the level of these hormones in birds that are ready for slaughter. Material and Methods: Throughout the incubation period, embryos from the experimental group were exposed to a 1800 MHz EMF with power density of 0.1 W/m2, 10 times during 24 h for 4 min. Blood samples were collected to determine T4, T3 and CORT concentrations on the 12th (E12 and 18th (E18 day of incubation, from newly hatched chicks (D1 and from birds ready for slaughter (D42. Results: The experiment showed that T4 and T3 concentrations decreased markedly and CORT levels increased in the embryos and in the newly hatched chicks exposed to EMF during embryogenesis. However, no changes were found in the level of the analyzed hormones in the birds ready for slaughter. Differences in T4 and T3 plasma concentrations between the EMF-exposed group and the embryos incubated without additional EMF were the highest in the newly hatched chicks, which may be indicative of the cumulative effect of electromagnetic field on the hypothalamo-pituitary-thyroid axis (HPT. Discussion: The obtained results suggest that additional 1800 MHz radio frequency electromagnetic field inhibits function of HPT axis, however, it stimulates hypothalamo- pituitary-adrenal axis by inducing adrenal steroidogenic cells to synthesize corticosterone. Further investigations are needed to elucidate the mechanisms by which radio EMFs affect HPT and HPA axis function in the chicken embryos.

  13. N=4 Supersymmetric Yang-Mills Theory on Orbifold-$T^4/{\\bf Z}_2$

    CERN Document Server

    Jinzenji, M; Jinzenji, Masao; Sasaki, Toru


    We derive the partition function of N=4 supersymmetric Yang-Mills theory on orbifold-$T^4/{\\bf Z}_2$. In classical geometry, K3 surface is constructed from the orbifold-$T^4/{\\bf Z}_2$. Along the same way as the orbifold construction, we construct the partition function of K3 surface from orbifold-$T^4/{\\bf Z}_2$. The partition function is given by the product of the contribution of the untwisted sector of $T^4/{\\bf Z}_2$, and that of the twisted sector of $T^4/{\\bf Z}_2$ i.e., ${\\cal O}(-2)$ curve blow-up formula.

  14. Contribution of local thyroxine monodeiodination to intracellular 3,5, 3'-triiodothyronine in several tissues of hyperthyroid rats at isotopic equilibrium

    Energy Technology Data Exchange (ETDEWEB)

    van Doorn, J.; van der Heide, D.; Roelfsema, F.


    The local conversion of T4 as a source of intracellular T3 in several organs of both hypothyroid and euthyroid rats has recently been recognized to be an important phenomenon. In the present study the source and quantity of T3 in various peripheral tissues of hyperthyroid rats were investigated. Athyreotic rats received a continuous iv infusion of T4 over a prolonged period in order to attain hyperthyroid conditions. At the same time, the animals also received a continuous iv infusion of (/sup 125/I)T4 and (/sup 131/I)T3 until isotopic equilibrium was achieved. After the animals were bled and perfused, the source and quantity of T3 in various tissue homogenates and subcellular preparations of liver, kidney, and the anterior pituitary gland were analyzed. In spite of the elevated plasma T3 and T4 levels, the concentration of T3 in the cerebral cortex and cerebellum was within the normal range. The contribution of T3 derived from local T4 to T3 conversion (Lc T3(T4)) was rather low in both parts of the brain when compared with values previously determined for euthyroid rats. Whereas previous studies revealed that Lc T3(T4) contributes significantly to the T3 in the pituitary glands of both hypothyroid and euthyroid rats, this was not the case for the hyperthyroid animals; virtually all T3 was derived from plasma. It was found that the T3 in muscle was derived exclusively from plasma. Both the liver and kidney showed high concentrations of T3. Whereas Lc T3(T4) was the main source of T3 in the liver, it contributed only a minor fraction of the total T3 content in the kidney.

  15. Profiles of Cortisol, Triiodothyronine, Thyroxine and Neutrophil/Lymphocyte Ratio as Stress Indicators in Swamp Buffaloes 15 Days Post-Transportation

    Directory of Open Access Journals (Sweden)

    H. Maheshwari


    Full Text Available Transportation may cause stress that affects livestock’s health. This research was conducted to observe the effect of transportation on the profiles of blood cortisol, triiodothyronine (T3, thyroxine (T4 and neutrophil/lymphocyte (N/L ratio as stress indicators during 15 days post-transportation. Four females swamp buffaloes, 2-yr-old were used in this research. The animals were transported using an open truck, along 15 kilometers distance for 2 h. During acclimatization, the animals were fed grass twice a day and access to water ad libitum. Blood was collected at the time of arrival and everyday for 15 d post-transportation. Cortisol, T3 and T4 were analyzed using Radioimmunoassay (RIA method. Blood smears were also prepared and stained with Giemsa for leukocyte differential counts. Results showed a significant relation (P1.5 in average throughout the period of the research. It is concluded that transportation causes stress and therefore changes metabolic process.

  16. T4-lysozyme fusion for the production of human formyl peptide receptors for structural determination. (United States)

    Wang, Xiaoqiang; Cui, Ying; Wang, Jiqian


    T4-lysozyme (T4L) fusion was introduced in the intracellular loop of a G protein-coupled receptor (GPCR) of human formyl peptide receptor 3 (FPR3), and the ability of T4L fusion to be used in the production of human FPR3 for structural determination was evaluated in this work. The T4L variant of human FPR3 termed FPR3-T4L was expressed in stable tetracycline-inducible HEK293 cells. A systematic detergent screening showed that fos-choline-14 was the optimal detergent to solubilize and subsequently purify FPR3-T4L from HEK293 cells. Immunoaffinity purification in combination with gel filtration was employed to purify the T4L-fused receptor to high homogeneity. The final yield of the human FPR3-T4L monomer from 2 g of cells was 0.2 mg. Circular dichroism spectroscopy indicated that the receptor adopted a correct secondary structure after purification, while ligand binding measurement indicated that the receptor was functional. Thus, the presence of T4L fusion did not evidently disturb the expression in HEK293 cells, proper folding, and functionality of human FPR3. Our study of evaluating T4L fusion for the recombinant production of human formyl peptide receptor would facilitate ongoing efforts in the structural characterization of GPCRs.

  17. Structural analysis of bacteriophage T4 DNA replication: a review in the Virology Journal series on bacteriophage T4 and its relatives

    Directory of Open Access Journals (Sweden)

    Boyer Ryan A


    Full Text Available Abstract The bacteriophage T4 encodes 10 proteins, known collectively as the replisome, that are responsible for the replication of the phage genome. The replisomal proteins can be subdivided into three activities; the replicase, responsible for duplicating DNA, the primosomal proteins, responsible for unwinding and Okazaki fragment initiation, and the Okazaki repair proteins. The replicase includes the gp43 DNA polymerase, the gp45 processivity clamp, the gp44/62 clamp loader complex, and the gp32 single-stranded DNA binding protein. The primosomal proteins include the gp41 hexameric helicase, the gp61 primase, and the gp59 helicase loading protein. The RNaseH, a 5' to 3' exonuclease and T4 DNA ligase comprise the activities necessary for Okazaki repair. The T4 provides a model system for DNA replication. As a consequence, significant effort has been put forth to solve the crystallographic structures of these replisomal proteins. In this review, we discuss the structures that are available and provide comparison to related proteins when the T4 structures are unavailable. Three of the ten full-length T4 replisomal proteins have been determined; the gp59 helicase loading protein, the RNase H, and the gp45 processivity clamp. The core of T4 gp32 and two proteins from the T4 related phage RB69, the gp43 polymerase and the gp45 clamp are also solved. The T4 gp44/62 clamp loader has not been crystallized but a comparison to the E. coli gamma complex is provided. The structures of T4 gp41 helicase, gp61 primase, and T4 DNA ligase are unknown, structures from bacteriophage T7 proteins are discussed instead. To better understand the functionality of T4 DNA replication, in depth structural analysis will require complexes between proteins and DNA substrates. A DNA primer template bound by gp43 polymerase, a fork DNA substrate bound by RNase H, gp43 polymerase bound to gp32 protein, and RNase H bound to gp32 have been crystallographically determined. The

  18. [Effect of Escherichia coli mutation affecting the RNA polymerase sigma factor on phage T4 development]. (United States)

    Zograf, Iu N


    The bacterial RNA polymerase sigma factor is necessary throughout T4 development. T4 can develop in the E. coli RpoD800 mutant cells only at permissive temperature. RNA synthesis in T4-infected mutant cells remains temperature-sensitive throughout infection as in uninfected mutant bacteria. This shows that bacterial sigma factor is necessary for all types of RNA synthesis in infected E. coli. The data obtained suggest also that active sigma factor is necessary for early, but not for late T4 DNA replication.

  19. [Hormone content of the blood plasma of rats after a flight on the Kosmos-1129 biosatellite]. (United States)

    Tigranian, R A; Kalita, N F; Macho, L; Kvetnanský, R


    The concentration of ACTH, insulin, glucagon, glucose, epinephrine, norepinephrine, thyrotrophic hormone, thyroxine, and triiodothyronine was measured in plasma of the rats flown for 18.5 days on Cosmos-1129. As a result of the flight, the concentration of insulin, thyrotrophic hormone, and triiodothyronine increased and that of thyroxine decreased. It is suggested that the above changes have been induced by an acute stress associated with biosatellite reentry and touchdown.

  20. Treatment with fixed thyroxine doses in pregnant women with subclinical hypothyroidism. (United States)

    Seoane Cruz, Inés; Penín Álvarez, Manuel; Luna Cano, Reyes; García-Mayor, Ricardo Víctor


    Hypothyroidism is usually treated with thyroxine doses on patient weight. In some cases, however, fixed doses have proved to useful to normalize TSH levels, which is especially important during pregnancy. Sixty-eight women diagnosed with subclinical hypothyroidism, autoimmune or not, during pregnancy were given a fixed dose of thyroxine 50 mcg/day. TSH measurements were performed to assess the need to change the dose, which was increased or decreased by 25 mcg/day when necessary. With a dose of 50 mcg/day of thyroxine, 42% of patients reached a TSH level less than 3 μU/mL, 79.4% reached a TSH level less than 4.5 μU/mL, and 20.6% had TSH levels higher than 4.5 μU/mL. Our data suggest that a fixed dose of thyroxine 50 mcg/day is inadequate in a significant proportion of pregnancy-diagnosed hypothyroidism regardless of whether the reference of TSH level used is 4.5 or 3 μU/mL. S starting dose of 75 mcg/day is probably more adequate, but studies are needed to evaluate the possibility of overtreatment with such dose. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

  1. Preparation of standards of triiodothyronine, thyroxine and thyrotropin; Prepracion de estandares de triyodotironina, tiroxina y tirotrofina

    Energy Technology Data Exchange (ETDEWEB)

    Lavalley E, C.; Delgado S, B.; Ruiz J, A.; Zambrano A, F


    The standards preparation requires of certain basic principles, some of which are described in this work, which was made with the purpose of establishing the most appropriate conditions for the preparation of standards of triiodothyronine, thyroxine and thyrotropin to be used in radioimmunoanalysis essays. The diverse standards show a balanced displacement, that which is observed in the graphs presented in this work. (Author)

  2. Maternal Thyroxine Levels During Pregnancy and Outcomes of Cognitive Development in Children. (United States)

    Wang, Pingping; Gao, Jian; Zhao, Shihua; Guo, Yong; Wang, Zengfang; Qi, Feng


    Though there were many studies assessing the relationship between maternal thyroxine levels during pregnancy and cognitive development in children, there was still lack of evidence for the association from a comprehensive assessment of published data. To get a more comprehensive estimate of the influence of low maternal thyroxine levels on cognitive function, a meta-analysis of prospective cohort studies was performed. Two electronic databases, MEDLINE and EMBASE, were searched for relevant prospective cohort studies. Relative risks (RR) with 95% confidence intervals (95% CI) were pooled using random-effect model of meta-analysis to assess the risk of delayed cognitive development in children. Seven prospective cohort studies with a total of 8273 mother-child pairs were included into the meta-analysis. There was obvious between-study heterogeneity in the meta-analysis (I(2) = 69.6%). Meta-analysis of using random-effect model showed that low maternal thyroxine level was significantly associated with a threefold risk of delayed cognitive development in children (random RR = 3.08, 95% CI 1.83-5.18, P cognitive development in children (random RR = 3.76, 95% CI 2.14-6.58, P cognitive development in children. Low maternal thyroxine level is significantly associated with a threefold risk of delayed cognitive development in children.

  3. Proposal of a candidate international conventional reference measurement procedure for free thyroxine in serum.

    NARCIS (Netherlands)

    Thienpont, L.M.; Beastall, G.H.; Christofides, N.D.; Faix, J.D.; Ieiri, T.; Jarrige, V.; Miller, W.G.; Miller, R.; Nelson, J.C.; Ronin, C.; Ross, H.A.; Rottmann, M.; Thijssen, J.H.; Toussaint, B.


    In the present paper the IFCC WG-STFT recommends and provides the rationale to establish metrological traceability of serum free thyroxine (FT4) measurements to a candidate international conventional reference measurement procedure. It is proposed that this procedure be based on equilibrium dialysis

  4. Impact of adjusting for the reciprocal relationship between maternal weight and free thyroxine during early pregnancy.

    LENUS (Irish Health Repository)

    Haddow, James E


    Among euthyroid pregnant women in a large clinical trial, free thyroxine (FT4) measurements below the 2.5th centile were associated with a 17 lb higher weight (2.9 kg\\/m(2)) than in the overall study population. We explore this relationship further.

  5. Initial catch-up growth in children with hypothyroidism on thyroxine replacement therapy

    Directory of Open Access Journals (Sweden)

    Rajitha D


    Full Text Available Background: There is a paucity of observational data from India on initial catch up growth in hypothyroid children started on thyroxine replacement therapy. Methods: We retrospectively studied 44 children and adolescents (32 girls with a diagnosis of primary hypothyroidism i.e., (thyrotropin > 15 µIU/mL and thyroxine < 55ng/mL. All were started on treatment with oral thyroxine. The dose was adjusted to maintain thyrotropin between 0.5-5 µIU/mL. Height was measured at baseline and at each follow-up visit and height standard deviation scores (HtSDS were calculated. We studied the therapeutic benefit of thyroxine replacement therapy on growth in the initial couple of years of treatment. Results: Dose of thyroxine required to restore euthyroidism was 4.1±2.5 µg/kg body weight. The dose fell from 9.7±2.4 µg/kg body weight in infants to 3.0±1.5 µg/kg body weight in adolescence (p<0.001. Likewise, the dose per unit body surface area also fell consistently from 207 ± 70.3 µg/m2 in infants to only 89.3±17.9 µg/m2 in adolescents (p<0.001. The initial HtSDS was 2.0±1.5 and this improved by 0.4 to final value of 1.6±1.3 (p < 0.001 after an average follow up of 14.1±2.5 months. The mean catch-up growth velocity, weighted for the duration of follow-up was 7.7 cm/year. Conclusions: The HtSDS deficit because of hypothyroidism is partially regained in the first few years after treatment.

  6. Hoc protein regulates the biological effects of T4 phage in mammals. (United States)

    Dabrowska, Krystyna; Zembala, Maria; Boratynski, Janusz; Switala-Jelen, Kinga; Wietrzyk, Joanna; Opolski, Adam; Szczaurska, Katarzyna; Kujawa, Marek; Godlewska, Joanna; Gorski, Andrzej


    We previously investigated the biological, non-antibacterial effects of bacteriophage T4 in mammals (binding to cancer cells in vitro and attenuating tumour growth and metastases in vivo); we selected the phage mutant HAP1 that was significantly more effective than T4. In this study we describe a non-sense mutation in the hoc gene that differentiates bacteriophage HAP1 and its parental strain T4. We found no substantial effects of the mutation on the mutant morphology, and its effects on electrophoretic mobility and hydrodynamic size were moderate. Only the high ionic strength of the environment resulted in a size difference of about 10 nm between T4 and HAP1. We compared the antimetastatic activity of the T2 phage, which does not express protein Hoc, with those of T4 and HAP1 (B16 melanoma lung colonies). We found that HAP1 and T2 decreased metastases with equal effect, more strongly than did T4. We also investigated concentrations of T4 and HAP1 in the murine blood, tumour (B16), spleen, liver, or muscle. We found that HAP1 was rapidly cleared from the organism, most probably by the liver. Although HAP1 was previously defined to bind cancer cells more effectively (than T4), its rapid elimination precluded its higher concentration in tumours.

  7. RNA-Seq Transcriptome Analysis of Direction-Selective T4/T5 Neurons in Drosophila. (United States)

    Pankova, Katarina; Borst, Alexander

    Neuronal computation underlying detection of visual motion has been studied for more than a half-century. In Drosophila, direction-selective T4/T5 neurons show supralinear signal amplification in response to stimuli moving in their preferred direction, in agreement with the prediction made by the Hassenstein-Reichardt detector. Nevertheless, the molecular mechanism explaining how the Hassenstein-Reichardt model is implemented in T4/T5 cells has not been identified yet. In the present study, we utilized cell type-specific transcriptome profiling with RNA-seq to obtain a complete gene expression profile of T4/T5 neurons. We analyzed the expression of genes that affect neuronal computational properties and can underlie the molecular implementation of the core features of the Hassenstein-Reichardt model to the dendrites of T4/T5 neurons. Furthermore, we used the acquired RNA-seq data to examine the neurotransmitter system used by T4/T5 neurons. Surprisingly, we observed co-expression of the cholinergic markers and the vesicular GABA transporter in T4/T5 neurons. We verified the previously undetected expression of vesicular GABA transporter in T4/T5 cells using VGAT-LexA knock-in line. The provided gene expression dataset can serve as a useful source for studying the properties of direction-selective T4/T5 neurons on the molecular level.

  8. Assembly and dynamics of the bacteriophage T4 homologous recombination machinery

    Directory of Open Access Journals (Sweden)

    Morrical Scott W


    Full Text Available Abstract Homologous recombination (HR, a process involving the physical exchange of strands between homologous or nearly homologous DNA molecules, is critical for maintaining the genetic diversity and genome stability of species. Bacteriophage T4 is one of the classic systems for studies of homologous recombination. T4 uses HR for high-frequency genetic exchanges, for homology-directed DNA repair (HDR processes including DNA double-strand break repair, and for the initiation of DNA replication (RDR. T4 recombination proteins are expressed at high levels during T4 infection in E. coli, and share strong sequence, structural, and/or functional conservation with their counterparts in cellular organisms. Biochemical studies of T4 recombination have provided key insights on DNA strand exchange mechanisms, on the structure and function of recombination proteins, and on the coordination of recombination and DNA synthesis activities during RDR and HDR. Recent years have seen the development of detailed biochemical models for the assembly and dynamics of presynaptic filaments in the T4 recombination system, for the atomic structure of T4 UvsX recombinase, and for the roles of DNA helicases in T4 recombination. The goal of this chapter is to review these recent advances and their implications for HR and HDR mechanisms in all organisms.

  9. T3 may be a better agent than T4 in the critically ill hypothyroid patient: evaluation of transport across the blood-brain barrier in a primate model

    Energy Technology Data Exchange (ETDEWEB)

    Chernow, B.; Burman, K.D.; Johnson, D.L.; McGuire, R.A.; O' Brian, J.T.; Wartofsky, L.; Georges, L.P.


    Thyroid hormone transport across the blood brain barrier in hypothyroid patients is clinically important yet poorly understood. To study this question, 200 micrograms of thyroxine (T4), 100 micrograms of 3,5,3'-triiodothyronine (T3) and 100 micrograms of 3,3',5'-triiodothyronine (reverse T3) were administered separately to 3 baboons, first iv and at a later date intrathecally (IT). Six animals were used. Three received the iv injections and three received the IT injections. In each of the 18 experiments, cerebrospinal fluid (CSF) and serum specimens were collected serially for 6 h after injection. Mean maximal elevations from baseline in CSF iodothyronine levels were 100 +/- 10 ng/dl after iv T4, 3921 +/- 293 ng/dl after iv T3 and 31 +/- 17 ng/dl after iv reverse T3. When given IT in the same dosages, the mean maximal increases in serum iodothyronine concentrations were: 1670 +/- 600 ng/dl for T4, 806 +/- 405 ng/dl for T3, and 210 +/- 43 ng/dl for reverse T3. In every animal studied, rapid bidirectional transfer of T3 from serum to CSF and CSF to serum occurred, whereas iv T4 resulted in delayed minimal increments in CSF T4 concentration. Isotopic experiments were also performed and the results analyzed using a kinetic model. When /sup 125/I-T3 was given iv, the equilibrium point in CSF was observed within 90 min with 1.7% of the administered dose/L able to be counted in CSF at any moment in time. When labeled T4 was given iv, only 0.6% of the administered dose/L was counted in CSF and the equilibrium point was not reached until 360 min. These data suggest: T4, T3, and reverse T3 are all capable of bidirectional transfer across the blood brain barrier, T3 may be a better agent than T4 in treating patients with myxedema coma because T3 crosses more rapidly and more completely from serum to CSF.

  10. AtlasT4SS: A curated database for type IV secretion systems

    Directory of Open Access Journals (Sweden)

    Souza Rangel C


    Full Text Available Abstract Background The type IV secretion system (T4SS can be classified as a large family of macromolecule transporter systems, divided into three recognized sub-families, according to the well-known functions. The major sub-family is the conjugation system, which allows transfer of genetic material, such as a nucleoprotein, via cell contact among bacteria. Also, the conjugation system can transfer genetic material from bacteria to eukaryotic cells; such is the case with the T-DNA transfer of Agrobacterium tumefaciens to host plant cells. The system of effector protein transport constitutes the second sub-family, and the third one corresponds to the DNA uptake/release system. Genome analyses have revealed numerous T4SS in Bacteria and Archaea. The purpose of this work was to organize, classify, and integrate the T4SS data into a single database, called AtlasT4SS - the first public database devoted exclusively to this prokaryotic secretion system. Description The AtlasT4SS is a manual curated database that describes a large number of proteins related to the type IV secretion system reported so far in Gram-negative and Gram-positive bacteria, as well as in Archaea. The database was created using the RDBMS MySQL and the Catalyst Framework based in the Perl programming language and using the Model-View-Controller (MVC design pattern for Web. The current version holds a comprehensive collection of 1,617 T4SS proteins from 58 Bacteria (49 Gram-negative and 9 Gram-Positive, one Archaea and 11 plasmids. By applying the bi-directional best hit (BBH relationship in pairwise genome comparison, it was possible to obtain a core set of 134 clusters of orthologous genes encoding T4SS proteins. Conclusions In our database we present one way of classifying orthologous groups of T4SSs in a hierarchical classification scheme with three levels. The first level comprises four classes that are based on the organization of genetic determinants, shared homologies, and

  11. pp-GalNAc-T4表达载体的构建

    Institute of Scientific and Technical Information of China (English)

    李喆; 郭向红; 吴士良


    目的 构建pp - GalNAc - T4的正义表达载体.方法 采用质粒转染法构建真核表达载体.结果 构建了pp -GalNAc-T4的正义表达载体,并得到了鉴定.结论 构建了pp - GalNAc - T4的正义表达载体,研究发现了在pp - GalNAc - T4c DNA转染NB4细胞株后,在mRNA水平及蛋白水平能稳定上调pp-GalNAc-T4的表达,可以用于以后的研究.

  12. One-step assay for the quantification of T4 DNA ligase. (United States)

    Franke, Steffi; Kreisig, Thomas; Buettner, Karin; Zuchner, Thole


    As one of the most commonly used enzyme in molecular biology, the T4 DNA ligase presents an important tool for the manipulation of DNA. T4 DNA ligase activity measurements are based on the use of radioactivity or rather labor-intense procedures including gel-based analysis. We therefore established a homogeneous T4 DNA ligase assay utilizing a specifically designed fluorescein- and dark quencher-labeled DNA molecule. Upon ligation of both DNA molecules, a quenching occurs and the fluorescence intensity decreases with increasing ligase concentrations. The assay allows a sensitive and precise quantification (CV, 4.6-5.5 %) of T4 DNA ligase activities and showed a high specificity when tested against other ligases of related and different species. Most importantly, this T4 DNA ligase assay requires only one working and incubation step before measurement can take place at room temperature and may therefore offer an interesting alternative to existing, more laborious ligase assays.

  13. T4 DNA连接酶酶活力测定方法%Detection methods of activity of T4 DNA ligase

    Institute of Scientific and Technical Information of China (English)

    周李华; 叶德萍; 王智; 唐祥凯


    工具酶的酶活力检测是工具酶产品质量控制的关键,研究和建立工具酶酶活力的测定方法是工具酶产品标准化制定的重点和难点.该文采用改进的粘性末端单位测定T4 DNA连接酶酶活力.经验证,方法重复性好,稳定性佳,为建立T4 DNA连接酶质量检测标准奠定了基础.

  14. T4 RNA Ligase 2 truncated active site mutants: improved tools for RNA analysis

    Directory of Open Access Journals (Sweden)

    Zhuang Fanglei


    Full Text Available Abstract Background T4 RNA ligases 1 and 2 are useful tools for RNA analysis. Their use upstream of RNA analyses such as high-throughput RNA sequencing and microarrays has recently increased their importance. The truncated form of T4 RNA ligase 2, comprising amino acids 1-249 (T4 Rnl2tr, is an attractive tool for attachment of adapters or labels to RNA 3'-ends. Compared to T4 RNA ligase 1, T4 Rnl2tr has a decreased ability to ligate 5'-PO4 ends in single-stranded RNA ligations, and compared to the full-length T4 Rnl2, the T4 Rnl2tr has an increased activity for joining 5'-adenylated adapters to RNA 3'-ends. The combination of these properties allows adapter attachment to RNA 3'-ends with reduced circularization and concatemerization of substrate RNA. Results With the aim of further reducing unwanted side ligation products, we substituted active site residues, known to be important for adenylyltransferase steps of the ligation reaction, in the context of T4 Rnl2tr. We characterized the variant ligases for the formation of unwanted ligation side products and for activity in the strand-joining reaction. Conclusions Our data demonstrate that lysine 227 is a key residue facilitating adenylyl transfer from adenylated ligation donor substrates to the ligase. This reversal of the second step of the ligation reaction correlates with the formation of unwanted ligation products. Thus, T4 Rn2tr mutants containing the K227Q mutation are useful for reducing undesired ligation products. We furthermore report optimal conditions for the use of these improved T4 Rnl2tr variants.

  15. Genomic characteristics and environmental distributions of the uncultivated Far-T4 phages

    Directory of Open Access Journals (Sweden)

    Simon eRoux


    Full Text Available Viral metagenomics (viromics is a tremendous tool to reveal viral diversity and ecosystem functional roles across ecosystems ranging from the human gut to the world's oceans. As with microbes however, there appear vast swaths of 'dark matter' yet to be documented for viruses, even among relatively well-studied viral types. Here, we use viromics to explore the 'Far-T4 phages' sequence space, a neighbor clade from the well-studied T4-like phages that was first detected through PCR study in seawater and subsequently identified in freshwater lakes through 454-sequenced viromes. To advance the description of these viruses beyond this single marker gene, we explore Far-T4 genome fragments assembled from 2 deeply-sequenced freshwater viromes. Single gene phylogenetic trees confirm that the Far-T4 phages are divergent from the T4-like phages, genome fragments reveal largely collinear genome organization, and both data led to the delineation of 5 Far-T4 clades. Three-dimensional models of major capsid proteins are consistent with a T4-like structure, and highlight highly conserved core flanked by variable insertions. Finally, we contextualize these now better characterized Far-T4 phages by re-analyzing 196 previously published viromes. These suggest that Far-T4 are common in freshwater and seawater as only 4 of 82 aquatic viromes lacked Far-T4-like sequences. Variability in representation across the 5 newly identified clades suggests clade-specific niche differentiation may be occurring across the different biomes, though the underlying mechanism remains unidentified. While complete genome assembly from complex communities and the lack of host linkage information still bottleneck virus discovery through viromes, these findings exemplify the power of metagenomics approaches to assess the diversity, evolutionary history, and genomic characteristics of novel uncultivated phages.

  16. Difference of the in vivo responsiveness to thyrotropin stimulation between the neotenic and metamorphosed axolotl, Ambystoma mexicanum: failure of prolactin to block the thyrotropin-induced thyroxine release. (United States)

    Darras, V M; Kühn, E R


    Basal and TSH-induced plasma concentrations of T4 have been measured by radioimmunoassay in the neotenic and metamorphosed male axolotl Ambystoma mexicanum both before and after an ovine prolactin pretreatment. All injections are made into the vena abdominalis. Basal levels of T4 are low in neotenes (85 +/- 19 pg/ml) and somewhat higher in metamorphosed Ambystoma (171 +/- 39 pg/ml), but are increased during metamorphosis (1094 +/- 138 pg/ml). Following injection of 5 mU bovine TSH circulating levels of T4 are raised about 4 times in neotenes, but more than 50 times in metamorphose animals. Three intravenous injections, each of 640 mU prolactin and given, respectively, 24 and 13 hr before and simultaneously with 5 mU TSH, do not inhibit the TSH-induced release in both experimental groups. In the metamorphosed Ambystoma again a more than 50-fold T4 increase is present, whereas in neotenes a 10-fold TSH-induced T4 release is seen, which is more pronounced than before the prolactin treatment. It is concluded that in A. mexicanum ovine prolactin does not block a TSH-induced T4 release and that any antagonistic action with thyroid hormones is not mediated through the thyroid gland.

  17. Effects of long-term temperature acclimation on thyroid hormone deiodinase function, plasma thyroid hormone levels, growth, and reproductive status of male Atlantic cod, Gadus morhua. (United States)

    Cyr, D G; Idler, D R; Audet, C; McLeese, J M; Eales, J G


    The recent collapse of the Northwestern Atlantic cod fisheries has coincided with a cooling of water temperatures. During this time the condition factor of cod has been poor. The objective of the present study was to determine the effects of long-term temperature acclimation on growth reproduction and thyroid function in laboratory held Atlantic cod (Gadus morhua). One of the key parameters used to assess thyroid function is the peripheral metabolism of L-thyroxine (T4) by microsomal deiodinase enzymes. Deiodinase function has not been described for gadid fish. T4 outer-ring deiodinating activity (apparent K(m) 1-2 nM) was confined primarily to liver. Its properties resembled those for hepatic T4ORD activity of other teleosts and the mammalian type II deiodinase. The T4ORD activity of cod liver exceeded that of salmonids and could explain the high plasma T3 levels (10-18 ng/ml), which were 2-5 times greater than T4 levels. T4 and T3 inner-ring deiodination was confined mainly to brain. In order to determine the effects of long-term temperature acclimation on cod, somatic growth, reproduction, and thyroidal status were assessed monthly in 400-900-g satiation-fed male Atlantic cod captured in June from the St. Lawrence Estuary and then acclimated from August to the following June under a natural photoperiod at 2-4 degrees C (LT) or 6-10 degrees C (HT). Reproductive status was determined from the gonadosomatic index (GSI), plasma testosterone (T) and 11-ketotestosterone (11-KT) levels, and the appearance of milt; thyroidal status was determined from plasma T4 and 3,5,3'-triiodo-L-thyronine (T3) levels and hepatic T4ORD activity to produce biologically active T3. Testis maturation (high levels of 1 and 11-KT, and milt release) occurred in April and May and was uninfluenced by acclimation temperature. LT cod grew more slowly than HT cod. Differences in body weight were particularly evident from December to February. In conclusion, (i) cod possess outer- and inner

  18. Evaluatie van de Coat-A-Count Neonatal T4 RIA en een vergelijking met de (125-I) Neonatal T4 RIA

    NARCIS (Netherlands)

    Elvers LH; Smit PJ; Loeber JG


    De Bijzondere Afd. Automatisering Serologisch Onderzoek maakt voor de screening op congenitale hypothyreoidie gebruik van de (125-I) Neonatal T4 RIA (LP) van Diagnostic Products Corporation (DPC). Vanaf maart 1984 zal deze kit echter niet meer geleverd worden. DPC heeft namelijk een nieuwe kit ge

  19. The Effects of the Recombinant CCR5 T4 Lysozyme Fusion Protein on HIV-1 Infection.

    Directory of Open Access Journals (Sweden)

    Qingwen Jin

    Full Text Available Insertion of T4 lysozyme (T4L into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed.We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects.Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1 infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5.Our results suggest that recombinant CCR5-T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents.

  20. Effect of protein and protein-free energy intake on plasma concentrations of insulin-like growth factor I and thyroid hormones in preruminant calves

    NARCIS (Netherlands)

    Gerrits, W.J.J.; Decuypere, E.; Verstegen, M.W.A.; Karabinas, V.


    We conducted two experiments with preruminant calves weighing 80 to 240 kg to study the long-term nutritional regulation of circulating IGF-I, thyroxine (T4), and triiodothyronine (T3). The two experiments were similar in design but were performed with calves of two live weight ranges: 80 to 160 kg

  1. Effect of Duration of Cold Stress on Plasma Adrenal and Thyroid Hormone Levels and Immune Responses in Chicken Lines Divergently Selected for Antibody Responses

    NARCIS (Netherlands)

    Hangalapura, B.N.; Nieuwland, M.G.B.; Buyse, J.; Kemp, B.; Parmentier, H.K.


    There is increasing evidence that stress affects various immune processes. Some of these changes are due to hormonal changes involving corticosterone (CORT), triiodothyronine (T3), and thyroxine (T4). Effects of stress depend on the nature of specific stressors (e.g., thermal extremes, diet, polluta

  2. Exploitation of Digital Filters to Advance the Single-Phase T/4 Delay PLL System

    DEFF Research Database (Denmark)

    Yang, Yongheng; Zhou, Keliang; Blaabjerg, Frede


    is demonstrated on a T/4 Delay Phase Locked Loop (PLL) system for a single-phase grid-connected inverter. The T/4 Delay PLL requires to cascade 50 unit delays when implemented (for a 50-Hz system with 10 kHz sampling frequency). Furthermore, digital frequency adaptive comb filters are adopted to enhance...... the performance of the T/4 Delay PLL when the grid suffers from harmonics. Experimental results have confirmed the effectiveness of the digital filters for advanced control systems....

  3. N-terminal T4 lysozyme fusion facilitates crystallization of a G protein coupled receptor.

    Directory of Open Access Journals (Sweden)

    Yaozhong Zou

    Full Text Available A highly crystallizable T4 lysozyme (T4L was fused to the N-terminus of the β(2 adrenergic receptor (β(2AR, a G-protein coupled receptor (GPCR for catecholamines. We demonstrate that the N-terminal fused T4L is sufficiently rigid relative to the receptor to facilitate crystallogenesis without thermostabilizing mutations or the use of a stabilizing antibody, G protein, or protein fused to the 3rd intracellular loop. This approach adds to the protein engineering strategies that enable crystallographic studies of GPCRs alone or in complex with a signaling partner.


    Institute of Scientific and Technical Information of China (English)

    ZHOU Zinan; XIE Demin; ZHANG Jianguo; WU Qinyi; FENG Zhiliu


    A new peak at 39.0 ppm in the 13C-NMR spectrum of polybutadiene (PBD) was discovered.This peak is assigned to the fourth peak (T4) of trans-1,4-sequence marked with an asterisk as shown in Fig. 3 in the text.The occurrence of T4 carbon nuclei is strongly affected by their neighboring 1,2-units. So long as both contents of trans-1,4- and 1,2-units attain their proper amounts the peak (T4) with appear in the 13C-NMR spectrum of PBD.

  5. Thyrotoxic periodic paralysis due to excessive L-thyroxine replacement in a Caucasian man.

    LENUS (Irish Health Repository)

    Hannon, M J


    Thyrotoxic periodic paralysis is a potentially fatal complication of hyperthyroidism, more common in Asian races, which is defined by a massive intracellular flux of potassium. This leads to profound hypokalaemia and muscle paralysis. Although the paralysis is temporary, it may be lethal if not diagnosed and treated rapidly, as profound hypokalaemia may induce respiratory muscle paralysis or cardiac arrest. The condition is often misdiagnosed in the west due to its comparative rarity in Caucasians; however it is now increasingly described in Caucasians and is also being seen with increasing frequency in western hospitals due to increasing immigration and population mobility. Here we describe the case of a patient with panhypopituitarism due to a craniopharyngioma, who developed thyrotoxic periodic paralysis due to excessive L-thyroxine replacement. This disorder has been described in Asian subjects but, to our knowledge, thyrotoxic periodic paralysis secondary to excessive L-thyroxine replacement has never been described in Caucasians.

  6. Retina maturation following administration of thyroxine in developing rats: effects on polyamine metabolism and glutamate decarboxylase. (United States)

    Macaione, S; Di Giorgio, R M; Nicotina, P A; Ientile, R


    The effects of subcutaneous daily treatment with thyroxine on cell proliferation, differentiation, polyamines, and gamma-aminobutyric acid metabolism in the rat retina were studied during the first 20 postnatal days. The retinal layers of the treated rats displayed an enhanced cell differentiation which reached its maximum 9-12 days from birth; but this effect stopped very quickly and was finished by the 20th postnatal day. Primarily there was an increase in ornithine decarboxylase activity which was accompanied by an increase in putrescine, spermidine, and spermine levels. S-Adenosylmethionine decarboxylase was induced later than ODC; corresponding with the enhanced synaptogenesis, glutamate decarboxylase increased 15-fold between the fourth and 15th days. Our data are consistent with the hypothesis that thyroxine may exert some of its effects by inducing the enzymes which regulate polyamine metabolism and synaptogenesis.

  7. Antidotes to coumarins, isoniazid, methotrexate and thyroxine, toxins that work via metabolic processes. (United States)

    Bateman, D Nicholas; Page, Colin B


    Some toxins cause their effects by affecting physiological processes that are fundamental to cell function or cause systemic effects as a result of cellular interaction. This review focuses on four examples, coumarin anticoagulants, isoniazid, methotrexate and thyroxine from the context of management of overdose as seen in acute general hospitals. The current basic clinical pharmacology of the toxin, the clinical features in overdose and evidence base for specific antidotes are discussed. The treatment for this group is based on an understanding of the toxic mechanism, but studies to determine the optimum dose of antidote are still required in all these toxins except thyroxine, where treatment dose is based on symptoms resulting from the overdose.

  8. Prevalence of hematological abnormalities in patients with Sheehan's syndrome: response to replacement of glucocorticoids and thyroxine. (United States)

    Laway, Bashir Ahmad; Mir, Shahnaz Ahmad; Bashir, Mir Iftikhar; Bhat, Javid Rasool; Samoon, Jeelani; Zargar, Abdul Hamid


    Anemia and other hematological abnormalities are common in patients with Sheehan's syndrome. The response of these abnormalities to replacement of thyroxine and glucocorticoids is not clear. The aim of the present study was to document the profile of hematological abnormalities and response to treatment in patients with Sheehan's syndrome. Forty patients of Sheehan's syndrome and an equal number of age and parity matched healthy controls were studied for prevalence of hematological abnormalities. Hemoglobin concentration, hematocrit, red cell, white cell and platelet count were significantly decreased in patients with Sheehan's syndrome compared to controls. Frequency of anemia, leucopenia, thrombocytopenia and pancytopenia was significantly higher in these patients compared to controls. After achieving euthyroid and eucortisol state, there was a complete recovery of these hematological abnormalities. We conclude that anemia and other cytopenias are common in patients with Sheehan's syndrome and replacement with thyroxine and glucocorticoids results in complete recovery of these abnormalities.

  9. Thyroxine treatment for elderly patients with heart failure and sick euthyroid syndrome

    Institute of Scientific and Technical Information of China (English)

    Yi ZHU; Ling GONG; Kailei SHI; Jin LI; Zhaohui QIU; Wenliang LU; Yu ZHANG; Jianying YANG


    Objectives To evaluate the effect of thyroid hormone therapy with low dose of thyroxin on cardiac function in elderly patients with heart failure and sick euthyroid syndrome. Methods Forty-seven patients (33 males and 14 females, mean age 85.9+4.6 years,ranging from 80 to 99 years) with chronic heart failure (NYHA Ⅱ-Ⅳ) and low triiodothyronine (T3) state were randomly allocated to the treatment group or control group. The treatment group patients received oral administration of levothyroxine sodium (Euthyrox) 25-50mg/d in addition to conventional therapy of heart failure, whereas patients in control group were given conventional therapy only. Serum level of total T3 (TT3), free T3 (FT3), total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were determined. For both groups, left ventricular ejection fraction (LVEF) and stroke volume (SV) were assessed by two-dimensional echocardiography before and at 8 weeks after treatment. The changes of these parameters after the treatment were evaluated by adjusting heart rate in the two groups. Results The reduced serum T3 level in the treatment group was corrected after thyroid hormone therapy,and these patients had a significant improvement in cardiac function after treatment. By contrast, in the control group only changes of serum TT3 and TT4 levels and SV and LVEF after treatment were statistically significant. The heart rate-adjusted mean SV and LVEF in both groups were also increased, which was significantly greater in the treatment group than in the control group. Conclusion In the elderly patients with heart failure and sick euthyroid syndrome, addition of thyroxine at a low dosage to the conventional treatment could effectively improve the low T3 state and cardiac function independent of changes of heart rate.

  10. Interleukin-12 plasmid DNA delivery using l-thyroxine-conjugated polyethylenimine nanocarriers (United States)

    Dehshahri, Ali; Sadeghpour, Hossein; Kazemi Oskuee, Reza; Fadaei, Mahin; Sabahi, Zahra; Alhashemi, Samira Hossaini; Mohazabieh, Erfaneh


    In this study, l-thyroxine was covalently grafted on 25 kDa branched polyethylenimine (PEI), and the ability of the nano-sized polyplexes for transferring plasmid encoding interleukin-12 (IL-12) gene was evaluated. As there are several problems in systemic administration of recombinant IL-12 protein, local expression of the plasmid encoding IL-12 gene inside the tumor tissue has been considered as an effective alternative approach. The l-thyroxine-conjugated PEI polyplexes were prepared using pUMVC3-hIL12 plasmid, and their transfection activity was determined in HepG2 human liver carcinoma and Neuro2A neuroblastoma cell lines. The polyplexes characterized in terms of DNA condensation ability, particle size, zeta potential, and buffering capacity as well as cytotoxicity and resistance to enzyme digestion. The results revealed that l-thyroxine conjugation of PEI increased gene transfer ability by up to two fold relative to unmodified 25 kDa PEI, the gold standard for non-viral gene delivery, with the highest increase occurring at degrees of conjugation around 10 %. pDNA condensation tests and dynamic light scattering measurements exhibited the ability of PEI conjugates to optimally condense the plasmid DNA into polyplexes in the size range around 200 nm. The modified polymers showed remarkable buffering capacity and protection against enzymatic degradation comparable to that of unmodified PEI. These results suggest that l-thyroxine conjugation of PEI is a simple modification strategy for future investigations aimed at developing a targeting gene vehicle.

  11. Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics

    National Research Council Canada - National Science Library

    Glowinski, Frithjof; Holland, Carsten; Thiede, Bernd; Jungblut, Peter R; Meyer, Thomas F


    .... A major virulence determinant of H. pylori is the type IV secretion system (T4SS), which is used to inject the virulence factor CagA into the host cell, triggering a wide range of cellular signaling events...

  12. Dynamics and Predictors of Serum TSH and fT4 Reference Limits in Early Pregnancy

    DEFF Research Database (Denmark)

    Laurberg, Peter; Andersen, Stine Linding; Hindersson, Peter


    CONTEXT: Thyroid hormones are important developmental factors and levels should be adequate both in the pregnant woman and in the fetus. However, there is no consensus on maternal thyroid test reference limits in early pregnancy. OBJECTIVE: Estimation of week-to-week changes in and predictors...... of TSH and free T4 (fT4) reference limits in the first trimester of pregnancy. DESIGN: Measurement of TSH and fT4 in biobank sera collected in pregnancy weeks 5-19 from a random sample of the Danish National Birth Cohort that enrolled 101 032 pregnant in 1996-2002. SETTING: National cohort of pregnant...... women. PARTICIPANTS: Healthy participants (n = 6671) were identified and individual characteristics retrieved using interview data and data from Danish national health registers. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Reference limits for TSH and fT4 in each first trimester pregnancy week...

  13. Adsorption of T4 bacteriophages on planar indium tin oxide surface via controlled surface tailoring. (United States)

    Liana, Ayu Ekajayanthi; Chia, Ed Win; Marquis, Christopher P; Gunawan, Cindy; Gooding, J Justin; Amal, Rose


    The work investigates the influence of surface physicochemical properties of planar indium tin oxide (ITO) as a model substrate on T4 bacteriophage adsorption. A comparative T4 bacteriophage adsorption study shows a significant difference in bacteriophage adsorption observed on chemically modified planar ITO when compared to similarly modified particulate ITO, which infers that trends observed in virus-particle interaction studies are not necessarily transferrable to predict virus-planar surface adsorption behaviour. We also found that ITO surfaces modified with methyl groups, (resulting in increased surface roughness and hydrophobicity) remained capable of adsorbing T4 bacteriophage. The adsorption of T4 onto bare, amine and carboxylic functionalised planar ITO suggests the presence of a unique binding behaviour involving specific functional groups on planar ITO surface beyond the non-specific electrostatic interactions that dominate phage to particle interactions. The paper demonstrates the significance of physicochemical properties of surfaces on bacteriophage-surface interactions.

  14. Hexamine cobalt chloride promotes intermolecular ligation of blunt end DNA fragments by T4 DNA ligase.


    Rusche, J R; Howard-Flanders, P


    Hexamine cobalt chloride (HCC) increases the efficiency of blunt end ligation by T4 DNA ligase about 50 fold. Maximum stimulation occurs when standard buffers for ligation are supplemented with 1 mM HCC. All the ligation events are intermolecular regardless of the initial DNA concentration. In the presence of monovalent cations (eg. 25 mM KCl) HCC still increases the extent of T4 catalyzed ligation but intramolecular ligation products are also formed. Therefore, intermolecular ligation can be...

  15. A novel DNA joining activity catalyzed by T4 DNA ligase


    Western, L M; Rose, S..J.


    The use of T4 and E. coli DNA ligases in genetic engineering technology is usually associated with nick-closing activity in double stranded DNA or ligation of 'sticky-ends' to produce recombinant DNA molecules. We describe in this communication the ability of T4 DNA ligase to catalyze intramolecular loop formation between annealed oligodeoxyribonucleotides wherein Watson-Crick base pairing is absent on one side of the ligation site. Enzyme concentration, loop size, substrate specificity, and ...

  16. Antitumor activity of endogenous mFlt4 displayed on a T4 phage nanoparticle surface

    Institute of Scientific and Technical Information of China (English)

    Shun-xiang REN; Zhao-jun REN; Min-yi ZHAO; Xiao-bin WANG; Shu-guang ZUO; Feng YU


    Aim: Flt4 plays a key role in promoting tumor metastasis by stimulating solid tumor lymphangiogenesis. In this study,mouse Flt4 (mFlt4) was displayed on T4 phage in order to explore the feasibility of breaking immune tolerance to "selfantigens" and to evaluate the phage's antitumor activity.Methods: A T4 phage nanometer particle expressing mFlt4 on the surface was constructed for evaluation as a recombinant vaccine. The presence of the mFlt4 gene in the T4-mFlt4 recombinant vaccine was verified by PCR and Western blot analysis. The immunotherapeutic potential of T4-mFlt4 was tested in mice injected with Lewis lung carcinoma (LLC) cells. AntiFlt4 antibody producing B cells were detected by ELISPOT. The effects of T4-mFlt4 on lymphatic metastasis and lymphangiogenesis were investigated in a mouse antimetastasis assay and by Flt4 and CD105 immunohistochemistry.Results: The T4-mFlt4 recombinant vaccine demonstrated antitumor activity and elicited autoantibodies against mFlt4.Mice carrying LLC-derived tumors exhibited prolonged survival when given the vaccine compared with control-treated animals. The vaccine also inhibited lymphangiogenesis and tumor metastasis in the mouse models. However, T4-mFlt4 was not observed to inhibit tumor growth.Conclusion: The T4-mFlt4 recombinant vaccine induced protective antitumor immunity and antimetastasis against LLC.Induction of an autoimmune response directed against tumor progression merits further study as a new strategy for immunotherapy in cancer.

  17. On the role of the Escherichia coli RNA polymerase sigma factor in T4 phage development. (United States)

    Zograff, Y N


    The rpoD800 mutation causing the temperature sensitivity of Escherichia coli RNA polymerase sigma factor has been used to demonstrate that the bacterial sigma factor is necessary throughout T4 phage development. In T4-infected RpoD800 mutant cells RNA synthesis is equally depressed at restrictive temperature at early and late stages of infection. The results show the bacterial sigma factor to be necessary for the synthesis of all RNA types in infected cells.

  18. Effects of virus and host genes on recombination among ultraviolet-irradiated bacteriophage T4

    Energy Technology Data Exchange (ETDEWEB)

    Priemer, M.M.; Chan, V.L.


    The influence of the polA, uvrA, and recA genes of Escherichia coli on recombination among ultraviolet-irradiated T4 bacteriophages was determined with respect to recombination between rII markers and phage yield. The polA and uvrA gene products have no effect on these two aspects of phage DNA metabolism. A recA mutation does not significantly alter rII recombination frequencies in irradiated phage crosses, nor does it greatly change the yield of infectious particles in wild-type phage crosses or crosses in which the phage strains possess the v mutation. However, the same cross experiment performed with a pair of T4x mutants in a recA host demonstrates an 84% reduction in the phage yield in an unirradiated control cross. Furthermore, with increasing doses of uv irradiation, phage productivity of the T4x mutant declines at an accelerated rate compared to T4x/sup +/ strains crossed in recA cells. Multiplicity reactivation experiments in which wild-type or recombination-deficient (x or y) T4 phages infect wild-type or recombination-deficient (recA) host cells show that irradiated phages can only be reactivated in recA/sup +/ hosts, regardless of the bacteriophage genotype. These results indicate the involvement of the E. coli recA gene product in normal T4 replication and multiplicity reactivation.

  19. Systematic appraisal of lactose intolerance as cause of increased need for oral thyroxine. (United States)

    Cellini, Miriam; Santaguida, Maria Giulia; Gatto, Ilenia; Virili, Camilla; Del Duca, Susanna Carlotta; Brusca, Nunzia; Capriello, Silvia; Gargano, Lucilla; Centanni, Marco


    An increased need for T4 has been described in patients with different gastrointestinal disorders. However, there is a lack of systematic studies assessing the need for T4 in hypothyroid patients with lactose intolerance, a widespread and often occult disorder. The objective of the study was to assess the replacement T4 dose required in hypothyroid patients with lactose intolerance. This was a cohort study. The study was conducted at an outpatient endocrinology unit in a University Hospital. The replacement T4 dose has been analyzed, from 2009 to 2012, in 34 hypothyroid patients due to Hashimoto's thyroiditis and lactose intolerance and being noncompliant with a lactose-free diet. An individually tailored T4 dose was measured. In all patients with isolated Hashimoto's thyroiditis, target TSH (median TSH 1.02 mU/L) was obtained at a median T4 dose of 1.31 μg/kg/d. In patients with lactose intolerance, only five of 34 patients reached the desired TSH (median TSH 0.83 mU/L) with a similar T4 dose (1.29 μg/kg/d). In the remaining 29 patients, the T4 dose was progressively increased and the target TSH (median TSH 1.21 mU/L) was attained at a median T4 dose of 1.81 μg/kg/d (+38%, P < .0001). In six of these patients, other gastrointestinal disorders were diagnosed, and their median T4 requirement was higher (2.04 μg/kg/d; +55%; P = .0032). In the remaining 23 patients with isolated lactose intolerance, a median T4 dose of 1.72 μg/kg/d (+31% P < .0001) has been required to attain pharmacological thyroid homeostasis. These findings show that lactose intolerance significantly increased the need for oral T4 in hypothyroid patients.

  20. Plasma metabolites, ions and thyroid hormones levels, and hepatic enzymes׳ activity in Caspian roach (Rutilus rutilus caspicus) exposed to waterborne manganese. (United States)

    Hoseini, Seyyed Morteza; Hedayati, Aliakbar; Ghelichpour, Melika


    To investigate the effect of waterborne manganese on plasma biochemical characteristics in fish, Caspian roach (Rutilus rutilus caspicus) was exposed to 0 (control), 60 (M60), 150 (M150) and 300 (M300) mg/L water manganese for 96h. Thereafter, plasma biochemical characteristics were studied. Plasma glucose level significantly increased in M60 and decreased in M150 and M300 groups, compared to the control. M300 had significantly lower hematocrit compared to the control. Albumin remained unchanged after manganese exposure, however, the manganese-exposed fish showed significant increase in plasma total protein levels. M150 and M300 showed significant increase in the plasma cholesterol and triglyceride levels compared to the control and M60. M60 and M150 had significantly higher alkaline phosphatase (ALP) activity compared to the control. The manganese-exposed groups had significantly higher alanine aminotransferase (ALT) activity compared to the control. M150 and M300 had aspartate aminotransferase (AST) activity significantly higher than those of the control and M60. M300 had significantly higher triiodothyronine (T3) levels than the other groups. All manganese-exposed fish had significantly higher thyroxin (T4) levels than the control. The plasma levels of chloride showed a significant decrease in the manganese-exposed fish, compared to the control. M150 and M300 had significantly lower sodium levels, compared to the control. M60 and M150 had significantly lower plasma calcium levels compared to the other groups. It is concluded that clinical chemistry along with thyroid hormones levels can be the useful tools to monitor manganese toxicity in fish. The possible mechanisms involving in the biochemical changes were discussed.

  1. Direct observation of T4 lysozyme hinge-bending motion by fluorescence correlation spectroscopy. (United States)

    Yirdaw, Robel B; McHaourab, Hassane S


    Bacteriophage T4 Lysozyme (T4L) catalyzes the hydrolysis of the peptidoglycan layer of the bacterial cell wall late in the infection cycle. It has long been postulated that equilibrium dynamics enable substrate access to the active site located at the interface between the N- and C-terminal domains. Crystal structures of WT-T4L and point mutants captured a range of conformations that differ by the hinge-bending angle between the two domains. Evidence of equilibrium between open and closed conformations in solution was gleaned from distance measurements between the two domains but the nature of the equilibrium and the timescale of the underlying motion have not been investigated. Here, we used fluorescence fluctuation spectroscopy to directly detect T4L equilibrium conformational fluctuations in solution. For this purpose, Tetramethylrhodamine probes were introduced at pairs of cysteines in regions of the molecule that undergo relative displacement upon transition from open to closed conformations. Correlation analysis of Tetramethylrhodamine intensity fluctuations reveals hinge-bending motion that changes the relative distance and orientation of the N- and C-terminal domains with ≅ 15 μs relaxation time. That this motion involves interconversion between open and closed conformations was further confirmed by the dampening of its amplitude upon covalent substrate trapping. In contrast to the prevalent two-state model of T4L equilibrium, molecular brightness and number of particles obtained from cumulant analysis suggest that T4L populates multiple intermediate states, consistent with the wide range of hinge-bending angles trapped in the crystal structure of T4L mutants.

  2. Genomes of the T4-related bacteriophages as windows on microbial genome evolution

    Directory of Open Access Journals (Sweden)

    Miller Eric S


    Full Text Available Abstract The T4-related bacteriophages are a group of bacterial viruses that share morphological similarities and genetic homologies with the well-studied Escherichia coli phage T4, but that diverge from T4 and each other by a number of genetically determined characteristics including the bacterial hosts they infect, the sizes of their linear double-stranded (ds DNA genomes and the predicted compositions of their proteomes. The genomes of about 40 of these phages have been sequenced and annotated over the last several years and are compared here in the context of the factors that have determined their diversity and the diversity of other microbial genomes in evolution. The genomes of the T4 relatives analyzed so far range in size between ~160,000 and ~250,000 base pairs (bp and are mosaics of one another, consisting of clusters of homology between them that are interspersed with segments that vary considerably in genetic composition between the different phage lineages. Based on the known biological and biochemical properties of phage T4 and the proteins encoded by the T4 genome, the T4 relatives reviewed here are predicted to share a genetic core, or "Core Genome" that determines the structural design of their dsDNA chromosomes, their distinctive morphology and the process of their assembly into infectious agents (phage morphogenesis. The Core Genome appears to be the most ancient genetic component of this phage group and constitutes a mere 12-15% of the total protein encoding potential of the typical T4-related phage genome. The high degree of genetic heterogeneity that exists outside of this shared core suggests that horizontal DNA transfer involving many genetic sources has played a major role in diversification of the T4-related phages and their spread to a wide spectrum of bacterial species domains in evolution. We discuss some of the factors and pathways that might have shaped the evolution of these phages and point out several parallels

  3. Case report: When measured free T4 and free T3 may be misleading. Interference with free thyroid hormones measurements on Roche® and Siemens® platforms

    Directory of Open Access Journals (Sweden)

    Lewandowski Krzysztof C


    Full Text Available Abstract A 59-year old female patient presented with apathy and 6 kg weight gain. Investigations revealed severe primary hypothyroidism (TSH>100 μIU/ml. L-thyroxine (L-T4 was started and titrated up to 75 μg, once daily, with clinical improvement. Other investigations revealed very high titres of anti-thyroid peroxidase (anti-TPO and anti-thyroglobulin (anti-Tg antibodies. After three months, there was a fall in TSH to 12.74 μIU/ml, however, with unexpectedly high free T4 (FT4 - 6.8 ng/ml and free T3 (FT3 - 6.7 pg/ml concentrations [reference range (rr: 0.8-1.9 ng/ml and 1.5-4.1 pg/ml (Siemens®, respectively]. At this stage L-T4 was stopped, and this was followed by a rapid increase in TSH (to 77.76 μIU/ml and some decrease in FT4 and FT3, however FT4 concentration remained elevated (2.1 ng/ml. Following this, L-T4 was restarted. On admission to our Department, she was clinically euthyroid on L-T4, 88 μg, once daily. Investigations on Roche® platform confirmed mildly elevated TSH - 5.14 (rr: 0.27-4.2 μIU/ml with high FT4 [4.59 (rr: 0.93-1.7 ng/ml] and FT3 [4.98 (rr: 2.6-4.4 pg/ml] concentrations. Other tests revealed hypoechogenic ultrasound pattern typical for Hashimoto thyroiditis. There was no discrepancy in calculated TSH value following TSH dilution (101% recovery. Concentrations of FT4 and FT3 were assessed on the day of discontinuation of L-T4 and after four days by the means of Abbott® Architect I 1000SR platform. These revealed FT4 and FT3 concentrations within the reference range [e.g., FT4 - 1.08 ng/ml (rr: 0.7-1.48] vs 4.59 ng/ml (rr: 0.93-1.7, Roche®, FT3 - 3.70 pg/ml (rr: 1.71-3.71 vs 4.98 (rr: 2.6-4.4, Roche®], confirming assay interference. Concentrations of ferritin and SHBG were normal. Conclusions Clinicians must be aware of possible assay interference, including the measurements of FT4 and FT3 in the differential diagnosis of abnormal results of thyroid function tests that do not fit the patient clinical

  4. T4 DNA ligase is more than an effective trap of cyclized dsDNA. (United States)

    Yuan, Chongli; Lou, Xiong Wen; Rhoades, Elizabeth; Chen, Huimin; Archer, Lynden A


    T4 DNA ligase is used in standard cyclization assays to trap double-stranded DNA (dsDNA) in low-probability, cyclic or highly bent conformations. The cyclization probability, deduced from the relative yield of cyclized product, can be used in conjunction with statistical mechanical models to extract the bending stiffness of dsDNA. By inserting the base analog 2-aminopurine (2-AP) at designated positions in 89 bp and 94 bp dsDNA fragments, we find that T4 DNA ligase can have a previously unknown effect. Specifically, we observe that addition of T4 ligase to dsDNA in proportions comparable to what is used in the cyclization assay leads to a significant increase in fluorescence from 2-AP. This effect is believed to originate from stabilization of local base-pair opening by formation of transient DNA-ligase complexes. Non-specific binding of T4 ligase to dsDNA is also confirmed using fluorescence correlation spectroscopy (FCS) experiments, which reveal a systematic reduction of dsDNA diffusivity in the presence of ligase. ATP competes with regular DNA for non-covalent binding to the T4 ligase and is found to significantly reduce DNA-ligase complexation. For short dsDNA fragments, however, the population of DNA-ligase complexes at typical ATP concentrations used in DNA cyclization studies is determined to be large enough to dominate the cyclization reaction.

  5. Effects of 2'-O-methyl nucleotide on ligation capability of T4 DNA ligase. (United States)

    Zhao, Bin; Tong, Zhaoxue; Zhao, Guojie; Mu, Runqing; Shang, Hong; Guan, Yifu


    To further understand the ligation mechanism, effects of 2'-O-methyl nucleotide (2'-OMeN) on the T4 DNA ligation efficiency were investigated. Fluorescence resonance energy transfer assay was used to monitor the nick-joining process by T4 DNA ligase. Results showed that substitutions at 5'- and 3'-ends of the nick decreased the ligation efficiency by 48.7% ± 6.7% and 70.6% ± 4.0%, respectively. Substitutions at both 5'- and 3'-ends decreased the ligation efficiency by 76.6% ± 1.3%. Corresponding kinetic parameters, Vmax, Km, and kcat, have been determined in each case by using the Michaelis-Menten equation. The kinetic data showed that the 2'-OMeN substitutions reduced the maximal initial velocity and increased the Michaelis constant of T4 DNA ligase. Mismatches at 5'- and 3'-ends of the nick have also shown different influences on the ligation. Results here showed that the sugar pucker conformation at 3'-end impairs the ligation efficiency more profoundly than that at 5'-end. Different concentrations of Mg(2+), Ca(2+), K(+), Na(+), and ATP were also demonstrated to affect the T4 DNA ligase activity. These results enriched our knowledge about the effects of 2'-OMeN substitutions on the T4 DNA ligase.

  6. Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics

    Directory of Open Access Journals (Sweden)

    Frithjof eGlowinski


    Full Text Available Helicobacter pylori is a Gram-negative bacterial pathogen colonizing the human stomach. Infection with H. pylori causes chronic inflammation of the gastric mucosa and may lead to peptic ulceration and/or gastric cancer. A major virulence determinant of H. pylori is the type IV secretion system (T4SS, which is used to inject the virulence factor CagA into the host cell, triggering a wide range of cellular signaling events. Here, we used a phosphoproteomic approach to investigate tyrosine signaling in response to host-pathogen interaction, using stable isotope labeling in cell culture (SILAC of AGS cells to obtain a differential picture between multiple infection conditions. Cells were infected with wild type H. pylori P12, a P12ΔCagA deletion mutant, and a P12ΔT4SS deletion mutant to compare signaling changes over time and in the absence of CagA or the T4SS. Tryptic peptides were enriched for tyrosine (Tyr phosphopeptides and analysed by nano-LC-Orbitrap MS. In total, 58 different phosphosites were found to be regulated following infection. The majority of phosphosites identified were kinases of the MAPK familiy. CagA and the T4SS were found to be key regulators of Tyr phosphosites. Our findings indicate that CagA primarily induces activation of ERK1 and integrin linked factors, whereas the T4SS primarily modulates JNK and p38 activation.

  7. Solvent interactions and protein dynamics in spin-labeled T4 lysozyme. (United States)

    Stoica, I


    Aspects of T4 lysozyme dynamics and solvent interaction are investigated using atomically detailed Molecular Dynamics (MD) simulations. Two spin-labeled mutants of T4 lysozyme are analyzed (T4L-N40C and T4L-K48C), which have been found from electronic paramagnetic resonance (EPR) experiments to exhibit different mobilities at the site of spin probe attachment (N- and C-terminus of helix B, respectively). Similarities and differences in solvent distribution and diffusion around the spin label, as well as around exposed and buried residues within the protein, are discussed. The purpose is to capture possible strong interactions between the spin label (ring) and solvent molecules, which may affect EPR lineshapes. The effect of backbone motions on the water density profiles is also investigated. The focus is on the domain closure associated with the T4 lysozyme hinge-bending motion, which is analyzed by Essential Dynamics (ED). The N-terminus of helix B is found to be a "hinge" residue, which explains the high degree of flexibility and motional freedom at this site.

  8. Virtual unit delay for digital frequency adaptive T/4 delay phase-locked loop system

    DEFF Research Database (Denmark)

    Yang, Yongheng; Zhou, Keliang; Blaabjerg, Frede


    -controller/processor with a fixed sampling rate considering the cost and complexity, where the number of unit delays that have been adopted should be an integer. For instance, in conventional digital control systems, a single-phase T/4 Delay Phase-Locked Loop (PLL) system takes 50 unit delays (i.e., in a 50-Hz system...... Delay PLL system should be done in its implementation. This process will result in performance degradation in the digital control system, as the exactly required number of delays is not realized. Hence, in this paper, a Virtual Unit Delay (VUD) has been proposed to address such challenges to the digital...... T/4 Delay PLL system. The proposed VUD adopts linear interpolation polynomial to approximate the fractional delay induced by the varying grid frequency in such a way that the control performance is enhanced. The proposed VUD has been demonstrated on a digitally controlled T/4 Delay PLL system...

  9. Expression, Characterization and Antimicrobial Ability of a Variant T4 Lysozyme in Pichia pastoris

    Institute of Scientific and Technical Information of China (English)

    Ning SUN; Sanfeng CHEN; Xiangming XIE; Yueju WANG; Gangqiang LI; Nan WANG; Dehu LIU


    T4 lysozyme was engineered with disulfide bonds and expressed in Pichia pastoris. The secreted proteins were purified and made into powder by lyophiliza-tion. Recombinant protein purity was more than 70% measured by HPLC. The lytic activity of variant T4-lysozyme was measured by the lysis of the cel wal of Xan-thomonas oryzae pv. oryzae, X. oryzae pv. oryzicola, Ralstonia solanacearum comb. nov, Clavibacter michiganensis subsp. michiganensis, X. campestris pv. mal-vacearum, Fusarium oxysporium sp. vasinfectum, Verticil ium dahliae kleb. Inhibition zone assay showed that variant T4 lysozyme significantly inhibited X. o. oryzicola and X. c. malvacearum. The antifungal activities of this protein against F. o. vasin-fectum and V. d. kleb were also analyzed.

  10. Glycosylation and epitope mapping of the 5T4 glycoprotein oncofoetal antigen. (United States)

    Shaw, David M; Woods, Andrew M; Myers, Kevin A; Westwater, Caroline; Rahi-Saund, Veena; Davies, Michael J; Renouf, David V; Hounsell, Elizabeth F; Stern, Peter L


    The human 5T4 oncofoetal antigen is a focus for development of several antibody-directed therapies on the basis of the murine monoclonal antibody against 5T4 (mAb5T4), which recognizes a conformational epitope. 5T4 molecules are highly N-glycosylated transmembrane glycoproteins whose extracellular domain contains two regions of leucine-rich repeats (LRRs) and associated flanking regions, separated by an intervening hydrophilic sequence. Using a series of deletion and mutated cDNA constructs as well as chimaeras with the murine homologue, we have mapped the mAb5T4 epitope to the more membrane-proximal LRR2 or its flanking region. Analysis of the glycosylation of the seven consensus Asp-Xaa-Ser/Thr sites was consistent with all of the sites being glycosylated. A combination of two high-mannose chains (predominantly octasaccharide) and five mostly sialylated bi-, tri- and tetra-antennary complex chains with minor quantities of core fucose were detected. The two glycosylation sites, which are the most likely to have predominantly high-mannose chains, are in the only two regions that show significant differences between the human and the 81% identical mouse sequence. A site-directed mutation, which abolished glycosylation at one of these sites (position 192), did not alter antigenicity. The other, which is nearest to the N-terminus in the human, has an Asn-Leu-Thr to Asn-Leu-Leu conversion in the mouse, so cannot be glycosylated in the latter species. The large complex glycosylation at the other sites is likely to influence the antigenicity and tertiary structure generating the 5T4 epitope. PMID:11903056

  11. Exploitation of Digital Filters to Advance the Single-Phase T/4 Delay PLL System

    DEFF Research Database (Denmark)

    Yang, Yongheng; Zhou, Keliang; Blaabjerg, Frede


    will violate this design rule and it can become a major challenge for digital controllers. To deal with the above issue, this paper first exploits a virtual unit delay (z_v^-1) to emulate the viable sampling behavior in practical digital signal processors with a fixed sampling rate. This exploitation...... is demonstrated on a T/4 Delay Phase Locked Loop (PLL) system for a single-phase grid-connected inverter. The T/4 Delay PLL requires to cascade 50 unit delays when implemented (for a 50-Hz system with 10 kHz sampling frequency). Furthermore, digital frequency adaptive comb filters are adopted to enhance...


    Directory of Open Access Journals (Sweden)

    Ahmad Muzaki


    Full Text Available Thyroxin administration in tiger grouper larval rearing was conducted to determine its effect on development of digestive tract of the larvae. Newly hatched larvae were treated with 0 mg/L (control, 0.1 mg/L, and 0.2 mg/L of thyroxin for 2 hours in a 30 L tank before were transferred into a 1 m3 rearing tank. Samples were collected daily until 10 DAH and every 3 days until 40 DAH. Development of digestive tract was observed using histological method. For all treatments, the digestive tract was the same on 1 DAH and 2 DAH. The digestive tract of 1 DAH larvae was still closed and still in the form of a simple tube. The mouth, buccopharynx, liver, pancreas, and rectum were found on 2 DAH. On 3 DAH, the esophagus, stomach, intestines, and anus started to develop. At this stage, the digestive tract of larvae treated with and without thyroxin started to become distinguishable. Several goblet cells were noticed in the rectum of the treated larvae but not in the control. Digestive tract developed earlier in treated larvae compared to the control group, such as appearance of tongue, gill raker, fundic, and cardiac stomach development, formation of pharyngeal tooth, and gastric gland. Metamorphosis of larvae into juvenile on treated larvae occurred than that the control larvae earlier.

  13. Crystal Structure of the Phage T4 Recombinase UvsX and Its Functional Interaction with the T4 SF2 Helicase UvsW

    Energy Technology Data Exchange (ETDEWEB)

    Gajewski, Stefan; Webb, Michael R.; Galkin, Vitold; Egelman, Edward H.; Kreuzer, Kenneth N.; White, Stephen W. (Duke); (UV); (SJCH)


    Bacteriophage T4 provides an important model system for studying the mechanism of homologous recombination. We have determined the crystal structure of the T4 UvsX recombinase, and the overall architecture and fold closely resemble those of RecA, including a highly conserved ATP binding site. Based on this new structure, we reanalyzed electron microscopy reconstructions of UvsX-DNA filaments and docked the UvsX crystal structure into two different filament forms: a compressed filament generated in the presence of ADP and an elongated filament generated in the presence of ATP and aluminum fluoride. In these reconstructions, the ATP binding site sits at the protomer interface, as in the RecA filament crystal structure. However, the environment of the ATP binding site is altered in the two filament reconstructions, suggesting that nucleotide cannot be as easily accommodated at the protomer interface of the compressed filament. Finally, we show that the phage helicase UvsW completes the UvsX-promoted strand-exchange reaction, allowing the generation of a simple nicked circular product rather than complex networks of partially exchanged substrates.

  14. T4DNA连接酶对电转化效率的影响%Effects of T4 DNA ligase on the electroporation

    Institute of Scientific and Technical Information of China (English)

    王福利; 赵爱志; 韩月恒; 温伟红; 刘建平; 董青川; 秦卫军


    目的 探讨T4 DNA连接酶影响电转化效率的机制并寻找提高电转化效率的方法.方法 将1μg噬粒pDAN5加入到连接反应体系中并进行沉淀、热灭活以及酚氯仿抽提等各种处理后进行电转化.结果 热灭活、酚氯仿抽提、热灭活后沉淀及热灭活后酚氯仿抽提处理后的转化效率最高(4.6×108~5.3×108),其次是沉淀处理(4.8×107),未处理的转化效率最低(4.4×106).结论 T4 DNA连接酶的活性是导致电转化效率降低的主要原因,任何可以灭活该酶活性的方法均可显著地提高转化效率.

  15. 利培酮致甲状腺功能改变与糖脂代谢异常的相关性分析%Correlation analysis of risperidone-induced changes on serum thyroxin with disorders of glucose and lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    陈晓慧; 王彦青; 赵鹏辉; 徐东; 张淑芳; 赵倩


    Objective To study the correlation of risperidone-induced changes on serum thyroxin with changes on blood glucose and lipid. Methods 35 schizophrenia patients were given risperidone 1-6mg/d for 8 weeks. Triiodothyronine (T3), thyroxin (T4), free triiodothyronine (FT3), free thyroxin (FT4), glucose (GLU) and triglyceride (TG) of all patients were measured before and after treatment. Before and after treatment, T3, T4, FT3, FT4, GLU and TG were compared respectively (t test), and the correlation of T3, T4, FT3, FT4 changs with GLU and TG changes were analyzed (Pearson test). Results After 8 weeks treatment, there was no significant difference in T3 compared with pre-treatment. T4, FT4 and GLU were significantly decreased than before treatment(P<0.05, P<0.05, P<0.01);TG were significantly increased (P<0.05). Changes between T4, FT4 and GLU were positively correlated (P<0.01, and P < 0.05). Changes between T3, FT3 and GLU were not related. And changes between T3, FT3, T4, FT4 and GLU had no correlation. Conclusion Risperidone could reduce thyroid, glucose and elevated blood lipid. There were positive correlations between the decrease of thyroid and the reduce blood glucose.%目的:研究利培酮致血清甲状腺激素水平改变与血糖、血脂水平改变之间的相关性。方法给予35例精神分裂患者利培酮8周治疗,治疗前后分别测定血清三碘甲状腺原氨酸(T3)、甲状腺素(T4)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、血糖(GLU)和甘油三酯(TG)水平。分别对比治疗前后各因素水平的变化情况(t检验),并对因素水平改变差值之间进行相关性分析(Pearson检验)。结果与治疗前比,治疗后血清T3水平无统计学差异,T4、FT4水平显著降低(P<0.05);GLU水平和TG水平分别有极显著性降低和升高(P<0.01)。T4、FT4变化与GLU变化呈正相关,有统计学意义(P<0.01、P<0.05);T3、FT3变化

  16. Sequence characteristics of T4-like bacteriophage IME08 benome termini revealed by high throughput sequencing

    Directory of Open Access Journals (Sweden)

    An Xiaoping


    Full Text Available Abstract Background T4 phage is a model species that has contributed broadly to our understanding of molecular biology. T4 DNA replication and packaging share various mechanisms with human double-stranded DNA viruses such as herpes virus. The literature indicates that T4-like phage genomes have permuted terminal sequences, and are generated by a DNA terminase in a sequence-independent manner; Methods genomic DNA of T4-like bacteriophage IME08 was subjected to high throughput sequencing, and the read sequences with extraordinarily high occurrences were analyzed; Results we demonstrate that both the 5' and 3' termini of the IME08 genome starts with base G or A. The presence of a consensus sequence TTGGA|G around the breakpoint of the high frequency read sequences suggests that the terminase cuts the branched pre-genome in a sequence-preferred manner. Our analysis also shows that terminal cleavage is asymmetric, with one end cut at a consensus sequence, and the other end generated randomly. The sequence-preferred cleavage may produce sticky-ends, but with each end being packaged with different efficiencies; Conclusions this study illustrates how high throughput sequencing can be used to probe replication and packaging mechanisms in bacteriophages and/or viruses.

  17. Albuminuria is an independent risk factor of T4 elevation in chronic kidney disease (United States)

    Du, Xin; Pan, Binbin; Li, Wenwen; Zou, Yonghua; Hua, Xi; Huang, Wenjuan; Wan, Xin; Cao, Changchun


    This study was to explore the association between thyroid dysfunction and albuminuria. 581 cases with chronic kidney disease (CKD) were included in this study. The clinical characteristics consisted of sex, age, serum creatinine, urinary albumin-to-creatinine ratio (ACR), thyroid function were recorded. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI four-level race equation. Prevalence of different thyroid diseases was calculated by chi-square test. Levels of thyroid hormone were compared among different albuminuria groups by Kruskal-Wallis test. Spearman’s correlation was used to assess the association between albuminuria and thyroid hormone. Our study showed that total T4 and free T4 were significantly different among ACR 300 mg/g (P hs-CRP, smoking status, systolic blood pressure, diabetes mellitus, medication use for diabetes mellitus, eGFR, LDL-cholesterol, triglycerides, hypertension, and medication use for hypercholesterinemia. In conclusion, T4 was positively correlated with albuminuria, and it was completely not consistent with our anticipation. Further study is needed to elucidate the causation association between albuminuria and T4. PMID:28117377

  18. 26 CFR 1.702-3T - 4-Year spread (temporary). (United States)


    ... with or within which such short year ends. Example 9. Assume that P3 is a partnership with a taxable... (CONTINUED) INCOME TAXES Partners and Partnerships § 1.702-3T 4-Year spread (temporary). (a) Applicability. This section applies to a partner in a partnership if— (1) The partnership is required by section...

  19. The isolation and characterization of Stenotrophomonas maltophilia T4-like bacteriophage DLP6 (United States)

    Peters, Danielle L.; Stothard, Paul


    Increasing isolation of the extremely antibiotic resistant bacterium Stenotrophomonas maltophilia has caused alarm worldwide due to the limited treatment options available. A potential treatment option for fighting this bacterium is ‘phage therapy’, the clinical application of bacteriophages to selectively kill bacteria. Bacteriophage DLP6 (vB_SmoM-DLP6) was isolated from a soil sample using clinical isolate S. maltophilia strain D1571 as host. Host range analysis of phage DLP6 against 27 clinical S. maltophilia isolates shows successful infection and lysis in 13 of the 27 isolates tested. Transmission electron microscopy of DLP6 indicates that it is a member of the Myoviridae family. Complete genome sequencing and analysis of DLP6 reveals its richly recombined evolutionary history, featuring a core of both T4-like and cyanophage genes, which suggests that it is a member of the T4-superfamily. Unlike other T4-superfamily phages however, DLP6 features a transposase and ends with 229 bp direct terminal repeats. The isolation of this bacteriophage is an exciting discovery due to the divergent nature of DLP6 in relation to the T4-superfamily of phages. PMID:28291834

  20. Structural studies on metal-containing enzymes. T4 endonuclease VII and D. gigas formate dehydrogenase

    NARCIS (Netherlands)

    Raaijmakers, H.C.A.


    Many biological processes require metal ions, and many of these metal-ion functions involve metalloproteins. The metal ions in metalloproteins are often critical to the protein's function, structure, or stability. This thesis focuses on two of these proteins, bacteriophage T4 endonuclease VII (EndoV

  1. Low submetamorphic doses of dexamethasone and thyroxine induce complete metamorphosis in the axolotl (Ambystoma mexicanum) when injected together. (United States)

    Kühn, Eduard R; De Groef, Bert; Grommen, Sylvia V H; Van der Geyten, Serge; Darras, Veerle M


    Entanglement of functions between the adrenal (or interrenal) and thyroid axis has been well described for all vertebrates and can be tracked down up to the level of gene expression. Both thyroid hormones and corticosteroids may induce morphological changes leading to metamorphosis climax in the neotenic Mexican axolotl (Ambystoma mexicanum). In a first series of experiments, metamorphosis was induced with an injection of 25 microg T(4) on three alternate days as judged by a decrease in body weight and tail height together with complete gill resorption. This injection also resulted in elevated plasma concentrations of T(3) and corticosterone. Previous results have indicated that the same dose of dexamethasone (DEX) is ineffective in this regard (Gen. Comp. Endocrinol. 127 (2002) 157). In a second series of experiments low doses of T(4) (0.5 microg) or DEX (5 microg) were ineffective to induce morphological changes. However, when these submetamorphic doses were injected together, morphological changes were observed within one week leading to complete metamorphosis. It is concluded that thyroid hormones combined with corticosteroids are essential for metamorphosis in the axolotl and that only high doses of either thyroid hormone or corticosteroid can induce morphological changes when injected separately.

  2. New Insights into DNA Polymerase Function Revealed by Phosphonoacetic Acid-Sensitive T4 DNA Polymerases. (United States)

    Zhang, Likui


    The bacteriophage T4 DNA polymerase (pol) and the closely related RB69 DNA pol have been developed into model enzymes to study family B DNA pols. While all family B DNA pols have similar structures and share conserved protein motifs, the molecular mechanism underlying natural drug resistance of nonherpes family B DNA pols and drug sensitivity of herpes DNA pols remains unknown. In the present study, we constructed T4 phages containing G466S, Y460F, G466S/Y460F, P469S, and V475W mutations in DNA pol. These amino acid substitutions replace the residues in drug-resistant T4 DNA pol with residues found in drug-sensitive herpes family DNA pols. We investigated whether the T4 phages expressing the engineered mutant DNA pols were sensitive to the antiviral drug phosphonoacetic acid (PAA) and characterized the in vivo replication fidelity of the phage DNA pols. We found that G466S substitution marginally increased PAA sensitivity, whereas Y460F substitution conferred resistance. The phage expressing a double mutant G466S/Y460F DNA pol was more PAA-sensitive. V475W T4 DNA pol was highly sensitive to PAA, as was the case with V478W RB69 DNA pol. However, DNA replication was severely compromised, which resulted in the selection of phages expressing more robust DNA pols that have strong ability to replicate DNA and contain additional amino acid substitutions that suppress PAA sensitivity. Reduced replication fidelity was observed in all mutant phages expressing PAA-sensitive DNA pols. These observations indicate that PAA sensitivity and fidelity are balanced in DNA pols that can replicate DNA in different environments.

  3. Comparative effect of Citrus sinensis and carbimazole on serum T 4 , T 3 and TSH levels

    Directory of Open Access Journals (Sweden)

    Okon Uduak Uduak


    Full Text Available Background: There are previous independent reports on the anti-thyroid property of Citrus sinensis. This isoflavones and phenolic acid-rich natural agent is widely consumed as dietary supplement, thus the need to investigate its comparative effect with a standard anti-thyroid drug on T 4 , T 3 and thyroid stimulating hormone (TSH levels. Objective: To compare the effect of Citrus sinensis and carbimazole (CARB on blood levels of thyroid hormones (T 4 and T 3 and TSH. Materials and Methods: Male wistar albino rats weighing 100-150 g were employed in this research. The rats were randomly assigned to four groups of seven rats per group. Group I served as control and were administered distilled water while groups II-IV were administered with 1500 mg/kg of Citrus sinensis (fresh orange juice; FOJ, 0.1 μg/g of levothyroxine (LVT and 0.01 mg/g of CARB, respectively, per oral once daily for 28 days. The animals were sacrificed under chloroform anaesthesia and blood sample collected by cardiac puncture and processed by standard method to obtain serum. TSH, T 4 and T 3 were assayed with the serum using ARIA II automated radioimmunoassay instrument. Results: The results showed that TSH level was significantly (P < 0.05 decreased in LVT treated group compared with the FOJ group. T 4 was significantly (P < 0.05 decreased in the FOJ and CARB groups compared with the control and LVT groups. LVT significantly increased T 4 when compared with FOJ group. T 3 was significantly (P < 0.05 decreased in the CARB group compared with the control. Conclusion: These findings suggest that FOJ alters thyroid hormones metabolism to reduce their serum levels with a compensatory elevations of TSH level in a direction similar to CARB.

  4. Changes of serum thyroid hormone and plasma catecholamine of 16 th and 17 th Chinese Expeditioners in Antarctic environment

    Institute of Scientific and Technical Information of China (English)

    徐成丽; 朱广瑾; 薛全福; 祖淑玉


    The serum thyroid hormone and plasma catecholamine were examined in 18 male and 2 female members of the Chinese Antarctic Expedition ( who spent the 2000 or 2001 austral winter at the Great Wall Station). The changes of serum thyroid hormone i.e. total thyroxine ( TT4 ) and free T4 ( FT4 ) , total triodothyronine ( TT3 )and freeT3 ( FT3 ), thyroid stimulating hormone (TSH) and plasma eateeholamine,including norepinephrine ( NE), epinephrine (E) and dopamine (DA) , were investigated by Chemoluminescenee Immunoassay (CLIA) and High Performance Liquid Chromatography with electrochemical detection (HPLC-ECD). Samples were taken at different time: (1) 1 day before departure to Antarctica (16th expedition 1999/12/09; 17th expedition 2000/12/06). (2) 1 day after returned to China after living 54 weeks in Antarctica ( 16th expedition 2000/12/25; 17th expedition 2001/12/25 ).Comparing the data of before departure and returned, results showed that there was a significant decrease in the contents of TT4 ( P < 0.01 ) with no significant change in the content of TT3, FT3 and FT4. It was also found that the content of TSH increased significantly (P <0. 001 ); No significant changes of plasma NE and DA were found but the content of E decreased significantly ( P < 0. 001 ). The results indicated that the special Antarctic environment led to a restrain effect on the thyroid function and the level of plasma E in Antarctic expedition members. Both the thyroid and adrenal medulla system were associated in response to the Antarctic systemic stress.

  5. 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

    DEFF Research Database (Denmark)

    Nygaard, Birte


    Background: Data suggest symptoms of hypothyroidism persist in 5–10% of levothyroxine (L-T4)-treated hypothyroid patients with normal serum thyrotrophin (TSH). The use of L-T4 + liothyronine (L-T3) combination therapy in such patients is controversial. The ETA nominated a task force to review....... There is insufficient evidence that L-T4 + L-T3 combination therapy is better than L-T4 monotherapy, and it is recommended that L-T4 monotherapy remains the standard treatment of hypothyroidism. L-T4 + L-T3 combination therapy might be considered as an experimental approach in compliant L-T4-treated hypothyroid...

  6. Semi-automated competitive protein binding analysis of serum thyroxine on reusable Sephadex columns and its advantages over radioimmunoassay. (United States)

    Alexander, N M


    Competitive protein-binding analysis of serum thyroxine on small, reusable, Sephadex columns has been further studied and improved. The improved, semi-automated procedure results in reduced working time and costs. It has also been established that triiodothyronine crossreacts only 1/6 to 1/9 as well as thyroxine, and can be ignored because it represents only about 1/80 of the total serum iodothyronine content. The economic and methodological advantages of the improved method over radioammunoassay and other displacement assays are discussed.

  7. Role of cytosol receptor in regulation of deiodination of thyroxine to triiodothyronine in rat liver microsomal fraction

    Energy Technology Data Exchange (ETDEWEB)

    Nauman, A.; Vogtt, E.; Bardowska, U. (Centrum Medyczne Ksztalcenia Podyplomowego, Warsaw (Poland))


    It was shown that partially purified and concentrated thyroid hormones binding cytosol proteins inhibit in vitro deiodination of thyroxine to triiodothyronine. The similar effect was evoked by equivalent concentration of bovine albumine. These results show that cytosol binding proteins may indirectly, by acting on concentration of free thyroxine, regulate the rate of conversion reaction. Results of studies with dithiotreitol-SH group protecting compound - suggest the possibility of indirect interaction between the cytosol binding proteins and converting system. These interactions were also observed in the presence of albumine which suggest that such a mechanism is not specific for cytosol receptor only.

  8. Rapid and selective inner ring deiodination of thyroxine sulfate by rat liver deiodinase

    Energy Technology Data Exchange (ETDEWEB)

    Mol, J.A.; Visser, T.J.


    Previous studies have shown that the inner ring deiodination (IRD) of T3 and the outer ring deiodination (ORD) of 3,3'-diiodothyronine are greatly enhanced by sulfate conjugation. This study was undertaken to evaluate the effect of sulfation on T4 and rT3 deiodination. Iodothyronine sulfate conjugates were chemically synthetized. Deiodination was studied by reaction of rat liver microsomes with unlabeled or outer ring /sup 125/I-labeled sulfate conjugate at 37 C and pH 7.2 in the presence of 5 mM dithiothreitol. Products were analyzed by HPLC or after hydrolysis by specific RIAs. T4 sulfate (T4S) was rapidly degraded by IRD to rT3S, with an apparent Km of 0.3 microM and a maximum velocity (Vmax) of 530 pmol/min X mg protein. The Vmax to Km ratio of T4S IRD was increased 200-fold compared with that of T4 IRD. However, formation of T3S by ORD of T4S could not be observed. The rT3S formed was rapidly converted by ORD to 3,3'-T2 sulfate, with an apparent Km of 0.06 microM and a Vmax of 516 pmol/min X mg protein. The enzymic mechanism of the IRD of T4S was the same as that of the deiodination of nonsulfated iodothyronines, as shown by the kinetics of stimulation by dithiothreitol or inhibition by propylthiouracil. The IRD of T4S and the ORD of rT3 were equally affected by a number of competitive inhibitors, suggesting a single enzyme for the deiodination of native and sulfated iodothyronines. In conjunction with previous findings on the deiodination of T3S, these results suggest that sulfation leads to a rapid and irreversible inactivation of thyroid hormone.

  9. Median nerve conduction velocity and central conduction time measured with somatosensory evoked potentials in thyroxine-treated infants with Down syndrome

    NARCIS (Netherlands)

    van Trotsenburg, A. S. Paul; Smit, Bert J.; Koelman, Johannes H. T. M.; Sloot, Marijke Dekker-van der; Ridder, Jeannette C. D.; Tijssen, Jan G. P.; de Vijlder, Jan J. M.; Vulsma, Thomas


    OBJECTIVE. The aim of this study was to determine whether thyroxine treatment would improve nerve conduction in infants with Down syndrome. METHODS. A single-center, nationwide, randomized, double-blind, clinical trial was performed. Neonates with Down syndrome were assigned randomly to thyroxine (N

  10. The Effect of Tripterygium Wilfordii Monomer T4 on Rat Spermatid Nuclear Protein Transition

    Institute of Scientific and Technical Information of China (English)

    戴文平; 刘平; 陈啸梅; 薛社普


    Rat testis elongating spermatids and epididymal sperms were collected after 7 weeks of treatment with Tripterygium wilfordii monomer T4. Total nuclear basic protein (TNBP) was extracted from the elongating spermatid nuclei and the sperm nuclei isolated by sonication. Polyacrylamide gel electrophoresis has beep used to separate the TNBP and individual proteins were quantified by scanning microdensitometry. It was found that the content of protamine was reduced and the TH (Total Histones) /RP (Rat Protamine) ratios were increased following treatment in the testis elongating spermatids, and same result was found in the epididymal sperms. These results suggest that the interruption of nuclear protein transition of testis spermatids induced by T4 might cause aberrant epididymal sperm nuclear protein and lead to infertility. The relationship between protamine and fertility was discussed.

  11. Laparoscopic vs. open surgery for T4 colon cancer: A propensity score analysis. (United States)

    de'Angelis, Nicola; Vitali, Giulio Cesare; Brunetti, Francesco; Wassmer, Charles-Henri; Gagniere, Charlotte; Puppa, Giacomo; Tournigand, Christophe; Ris, Frédéric


    The study aimed to compare, using propensity score matching (PSM) analyses, the short- and long-term results of laparoscopic colectomy (LC) versus open colectomy (OC) in a bicentric cohort of patients with T4 colon cancer. This is a retrospective PSM analysis of consecutive patients undergoing elective LC or OC for pT4 colon cancer (TNM stage II/III) between 2005 and 2014. Overall, 237 patients were selected. After PSM, 106 LC-and 106 OC-matched patients were compared. LC was associated with longer operative time and lower blood loss than OC (220 vs. 190 min, p colon cancer similar to open surgery and can be considered a safe and feasible alternative approach that confers the advantage of a faster recovery.

  12. Purification of histidine-tagged T4 RNA ligase from E. coli. (United States)

    Wang, Qing S; Unrau, Peter J


    Here we report the construction of a histidine-tagged T4 RNA ligase expression plasmid (pRHT4). The construct, when overexpressed in BL21 (DE3) cells, allows the preparation of large quantities of T4 RNA ligase in high purity using only a single purification column. The histidine affinity tag does not inhibit enzyme function, and we were able to purify 1-3 mg pure protein/g cell pellet. A simple purification procedure ensures that the enzyme is de-adenylated to levels comparable to those found for many commercial preparations. The purified protein has very low levels of RNase contamination and functioned normally in a variety of activity assays.

  13. Effect of Plastic Anisotropy on the Formability of Aluminum 6016-T4 Sheet Material (United States)

    KIM, Young-Suk; YANG, Seung-Han


    Sheet metal formed of lightweight materials such as aluminum sheeting has received great attention related to the reduction of vehicle emissions. This paper evaluates the anisotropic yield locus using Kuwabara's biaxial tensile tester and stretches formability using Hecker's hemispherical punch stretching test for aluminum 6016-T4 sheet material. The anisotropic yield locus of the Al6016-T4 sheet measured is fitted well by the modified Drucker yield function. Moreover the best fitting to the experimental stress-strain curve from the tensile test was obtained by taking an appropriate hardening model. Analytical study to predict the stretch formability by using Hora's Modified Maximum Force Criterion (MMFC) was performed. The predicted forming limit curves (FLC) based on various yield functions were compared with the experiments and discussed.

  14. Repairing DNA damage in xeroderma pigmentosum: T4N5 lotion and gene therapy. (United States)

    Zahid, Sarwar; Brownell, Isaac


    Patients with xeroderma pigmentosum (XP) have defective DNA repair and are at a high risk for cutaneous malignancies. Standard treatments for XP are limited in scope and effectiveness. Understanding the molecular etiology of XP has led to the development of novel therapeutic approaches, including enzyme and gene therapies. One new topical treatment utilizing bacteriophage T4 endonuclease 5 (T4N5) in a liposomal lotion is currently in clinical trials and has received a Fast Track designation from the FDA. Gene therapy for XP, while making leaps in preclinical studies, has been slower to develop due to tactical hurdles, but seems to have much potential for future treatment. If these treatments prove effective in lowering the risk of cancer in patients with XP, they may also be found useful in reducing skin cancers in other at-risk patient populations.

  15. Shine-Dalgarno sequence of bacteriophage T4: GAGG prevails in early genes. (United States)

    Malys, Naglis


    Translation initiation is governed by a limited number of mRNA sequence motifs within the translation initiation region (TIR). In bacteria and bacteriophages, one of the most important determinants is a Shine-Dalgarno (SD) sequence that base pairs with the anti-SD sequence GAUCACCUCCUUA localized in the 3' end of 16S rRNA. This work assesses a diversity of TIR features in phage T4, focusing on the SD sequence, its spacing to the start codon and relationship to gene expression and essentiality patterns. Analysis shows that GAGG is predominant of all core SD motifs in T4 and its related phages, particularly in early genes. Possible implication of the RegB activity is discussed.

  16. Unexpected substrate specificity of T4 DNA ligase revealed by in vitro selection (United States)

    Harada, Kazuo; Orgel, Leslie E.


    We have used in vitro selection techniques to characterize DNA sequences that are ligated efficiently by T4 DNA ligase. We find that the ensemble of selected sequences ligates about 50 times as efficiently as the random mixture of sequences used as the input for selection. Surprisingly many of the selected sequences failed to produce a match at or close to the ligation junction. None of the 20 selected oligomers that we sequenced produced a match two bases upstream from the ligation junction.

  17. Prognostic factors of T4 gastric cancer patients undergoing potentially curative resection

    Institute of Scientific and Technical Information of China (English)

    Naoto Fukuda; Yasuyuki Sugiyama; Joji Wada


    AIM: To investigate the prognostic factors of T4 gas-tric cancer patients without distant metastasis who could undergo potentially curative resection. METHODS: We retrospectively analyzed the clinical data of 71 consecutive patients diagnosed with T4 gas-tric cancer and who underwent curative gastrectomy at our institutions. The clinicopathological factors that could be associated with overall survival were evalu-ated. The cumulative survival was determined by the Kaplan-Meier method, and univariate comparisons be-tween the groups were performed using the log-rank test. Multivariate analysis was performed using the Cox proportional hazard model and a step-wise procedure.RESULTS: The study patients comprised 53 men (74.6%) and 18 women (25.4%) aged 39-89 years (mean, 68.9 years). Nineteen patients (26.8%) had postoperative morbidity: pancreatic fistula developed in 6 patients (8.5%) and was the most frequent compli-cation, followed by anastomosis stricture in 5 patients (7.0%). During the follow-up period, 28 patients (39.4%) died because of gastric cancer recurrence, and 3 (4.2%) died because of another disease or accident. For all patients, the estimated overall survival was 34.1% at 5 years. Univariate analyses identified the following statis-tically significant prognostic factors in T4 gastric cancer patients who underwent potentially curative resection: peritoneal washing cytology (P < 0.01), number of met-astatic lymph nodes (P < 0.05), and venous invasion (P < 0.05). In multivariate analyses, only peritoneal wash-ing cytology was identified as an independent prognos-tic factor (HR = 3.62, 95% CI = 1.37-9.57) for long-term survival. CONCLUSION: Positive peritoneal washing cytology was the only independent poor prognostic factor for T4 gastric cancer patients who could be treated with potentially curative resection.

  18. Preoperative radiation therapy for upper rectal cancer T3,T4/Nx: selectivity essential. (United States)

    Popek, Sarah; Tsikitis, Vassiliki Liana; Hazard, Lisa; Cohen, Alfred M


    This review explores the current available literature regarding the role of neoadjuvant therapy for upper locally advanced rectal cancers (≥10 cm-15 cm). Although there is a paucity of data evaluating the outcomes of preoperative chemoradiation for upper rectal cancers the authors suggest that T3N0 tumors will not likely benefit from radiation and that treatment of T4N0 should be individualized. Copyright © 2012. Published by Elsevier Inc.

  19. Control of helicase loading in the coupled DNA replication and recombination systems of bacteriophage T4. (United States)

    Branagan, Amy M; Klein, Jenny A; Jordan, Christian S; Morrical, Scott W


    The Gp59 protein of bacteriophage T4 promotes DNA replication by loading the replicative helicase, Gp41, onto replication forks and recombination intermediates. Gp59 also blocks DNA synthesis by Gp43 polymerase until Gp41 is loaded, ensuring that synthesis is tightly coupled to unwinding. The distinct polymerase blocking and helicase loading activities of Gp59 likely involve different binding interactions with DNA and protein partners. Here, we investigate how interactions of Gp59 with DNA and Gp32, the T4 single-stranded DNA (ssDNA)-binding protein, are related to these activities. A previously characterized mutant, Gp59-I87A, exhibits markedly reduced affinity for ssDNA and pseudo-fork DNA substrates. We demonstrate that on Gp32-covered ssDNA, the DNA binding defect of Gp59-I87A is not detrimental to helicase loading and translocation. In contrast, on pseudo-fork DNA the I87A mutation is detrimental to helicase loading and unwinding in the presence or absence of Gp32. Other results indicate that Gp32 binding to lagging strand ssDNA relieves the blockage of Gp43 polymerase activity by Gp59, whereas the inhibition of Gp43 exonuclease activity is maintained. Our findings suggest that Gp59-Gp32 and Gp59-DNA interactions perform separate but complementary roles in T4 DNA metabolism; Gp59-Gp32 interactions are needed to load Gp41 onto D-loops, and other nucleoprotein structures containing clusters of Gp32. Gp59-DNA interactions are needed to load Gp41 onto nascent or collapsed replication forks lacking clusters of Gp32 and to coordinate bidirectional replication from T4 origins. The dual functionalities of Gp59 allow it to promote the initiation or re-start of DNA replication from a wide variety of recombination and replication intermediates.

  20. Pulsating strings from two-dimensional CFT on (T4N/S(N

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    Carlos Cardona


    Full Text Available We propose a state from the two-dimensional conformal field theory on the orbifold (T4N/S(N as a dual description for a pulsating string moving in AdS3. We show that, up to first order in the deforming parameter, the energy in both descriptions has the same dependence on the mode number, but with a non-trivial function of the coupling.

  1. Synthesis and magnetic property of T4 virus-supported gold-coated iron ternary nanocomposite

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    Xu Ziming; Sun Hongjing; Gao Faming, E-mail:; Hou Li; Li Na [Yanshan University, Key Laboratory of Applied Chemistry (China)


    Herein, we present a novel method based on the use of the symmetrical T4 bacteriophage capsid as a scaffold for preparing the gold-coated iron ternary core/shell nanostructure. Results showed that the thick gold shell was obtained to effectively protect Fe core from oxidation. Magnetic measurements showed that the nanocomposites were superparamagnetic at room temperature with a blocking temperature of about 35 K. At 3 K, its coercivity of 1142.86 Oe was larger than the existing experimental values. The magnetic property of Au/T4 was also tested, demonstrating the source of the magnetic sample arising from the Fe core only. The absorption spectrum of the Fe-Au/T4 complex was measured and compared with gold/virus. Different thickness gold shells were controlled in the synthesis by tuning the Au salt addition. On the basis of results and discussion, we further speculated the general growing mechanism of the template-supported Fe-Au process.

  2. T3/T4 thoracic sympathictomy and compensatory sweating in treatment of palmar hyperhidrosis

    Institute of Scientific and Technical Information of China (English)

    YANG Jie; TAN Jia-ju; YE Guo-lin; GU Wei-quan; WANG Jun; LIU Yan-guo


    Background Compensatory sweating (CS) is one of the most common postoperative complications after thoracic sympathectomy, sympathicotomy or endoscopic sympathetic block (ESB) for palmar hyperhidrosis. This study was conducted to examine the relevance between CS and the sympathetic segment being transected in the surgical treatment of palmar hyperhidrosis, and thus to detect the potential mechanism of the occurrence of CS.Methods Between October 2004 and June 2006, 163 patients with primary hyperhidrosis were randomly divided into two groups, T3 sympathicotomy (78 patients) and T4 sympathicotomy(85), who were operated upon under general anesthesia via single lumen intubation and intercostal video-mediastinoscopy (VM).Results No morbidity or mortality occurred. Palmar hyperhidrosis was cured in all patients. Follow-up(mean (13.8±6.2)months) showed no recurrence of palmar hyperhidrosis. The difference of rates of mild CS in groups T3 and T4 was of no statistical significance. The rate of moderate CS was significantly lower in group T4 than in group T3. No severe CS occurred.Conclusion The rates of occurrence and severity of CS are lowered with the lower sympathetic chain being transected.

  3. Efficient assembly of very short oligonucleotides using T4 DNA Ligase

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    Holt Robert A


    Full Text Available Abstract Background In principle, a pre-constructed library of all possible short oligonucleotides could be used to construct many distinct gene sequences. In order to assess the feasibility of such an approach, we characterized T4 DNA Ligase activity on short oligonucleotide substrates and defined conditions suitable for assembly of a plurality of oligonucleotides. Findings Ligation by T4 DNA Ligase was found to be dependent on the formation of a double stranded DNA duplex of at least five base pairs surrounding the site of ligation. However, ligations could be performed effectively with overhangs smaller than five base pairs and oligonucleotides as small as octamers, in the presence of a second, complementary oligonucleotide. We demonstrate the feasibility of simultaneous oligonucleotide phosphorylation and ligation and, as a proof of principle for DNA synthesis through the assembly of short oligonucleotides, we performed a hierarchical ligation procedure whereby octamers were combined to construct a target 128-bp segment of the beta-actin gene. Conclusions Oligonucleotides as short as 8 nucleotides can be efficiently assembled using T4 DNA Ligase. Thus, the construction of synthetic genes, without the need for custom oligonucleotide synthesis, appears feasible.

  4. Experimental electromagnetic effects on the model organism Escherichia coli and the bacteriophage T4 (United States)

    Lisiewski, Darlene Mildred

    This experimentally-based work was designed to answer the research question as to whether the phenomenon of nuclear magnetic resonance (NMR) can produce observable effects upon the bacterial virus activity of T4, with such activity demonstrated through the infection of its host bacterium Escherichia coli. The biological samples were placed for three hours within a coil antenna assembly propagating oscillating fields of radio frequency electromagnetic energy generated at the frequency of 5.6 MHz, and set at right angles within a magnetic field of 1450 gauss (recognizing such conditions are not set for the maximum effective resonance for hydrogen nuclei). The laboratory technique of plaque formation was the basis upon which the statistically tested data were compiled. Exposure of the bacterium alone exhibited an increase in viral activity over the control group (40--68% higher numbers of plaque formation), while exposure of T4 alone saw a decrease (approximately 23%) in infection rates. Depending on the protocol, placement of both T4 and E. coli into the coil assembly saw a decrease of either approximately 50% or 42% in infection rates. Future research must address identification of the effects being observed.

  5. Evidence that the heterogeneity of a T4 population is the result of heritable traits. (United States)

    Storms, Zachary J; Sauvageau, Dominic


    Many bacteriophage populations display heterogeneity in their adsorption characteristics; a portion of the phage population remains free in solution throughout adsorption experiments (residual fraction). This residual fraction generally constitutes a minority of phages that exhibit significantly slower adsorption kinetics than the main phage stock (main fraction). While this phenomenon is likely the result of evolutionary driving forces, the present study demonstrates that the residual fraction is not always the result of phenotypic variations within a single genotype, as is generally thought. Experiments with phage T4 showed that two subgroups with distinct adsorption traits that were passed on to their progeny could be isolated from the original phage stock. Sequencing of genes involved in adsorption revealed two point mutations in gene 37 of residual fraction isolates, which resulted in modifications to the long tail-fiber, the organelle of attachment and host cell recognition. Adsorption studies consistently showed that T4 phage stocks amplified from residual fraction isolates had significantly lower adsorption efficiencies than those amplified from main fractions. The conducted experiments provide convincing evidence that the observed heterogeneity in T4 adsorption behavior is the result of conserved mutations to the phage genome and is not exclusively the result of phenotypic variations within the population. While it is believed high mutation rates exist to hasten phage adaptation, this study shows that this bet hedging strategy can also, in the short term, inadvertently handicap the phage's adsorption capabilities to a given host under normal infection conditions, resulting in the residual fraction observed in adsorption experiments.

  6. Introduction of Ca(2+)-binding amino-acid sequence into the T4 lysozyme. (United States)

    Leontiev, V V; Uversky, V N; Permyakov, E A; Murzin, A G


    The 51-62 loop of T4 phage lysozyme was altered by site-directed mutagenesis to obtain maximal homology with the typical EF-hand motif. A Ca(2+)-binding site was designed and created by replacing both Gly-51 and Asn-53 with aspartic acid. The mutant T4 lysozyme (G51D/N53D) was expressed in Escherichia coli. The activity of the G51D/N53D-mutant was about 60% of that of the wild-type protein. This mutant can bind Ca2+ ions specifically, while the effective dissociation constant was essentially greater than that of the EF-hand proteins. Stability of the G51D/N53D-mutant apo-form to urea- or temperature-induced denaturation was the same as that of the wild-type protein. In the presence of Ca2+ ions in solution the stability of the mutant T4 phage lysozyme was less than that of the wild-type protein. It is suggested that the binding of Ca2+ by the mutant is accompanied by the considerable conformational changes in the 'corrected' loop, which can lead to the Ca(2+)-induced destabilization of the protein.

  7. Palliative telecobalt-60 with concentrated dose in TNM classification T4 of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Patricio, M.B.; Brites, C.F.; Guimaraes, M.F.; De Jesus, E.B.; Catita, J.I.; Vilhena, M.


    A method is presented of rapid, palliative radiotherapy for carcinoma of the breast, composed of two sessions of 6.5 or 8.5 Gy delivered at a 48-hour interval. The radiobiological equivalence of this unconventional technique is presented. Our preliminary results in a series of 80 patients were published in 1978. The present report is based on the analysis of 112 patients with T4 of the breast submitted to the flash dose, from March 1978 to December 1981. The method was used not only for relief of symptoms such as pain and hemorrhage, but also as part of intensive radiotherapy in all patients with good response and with no manifestation of distant dissemination so that they were able to resume treatment 2.5 or 3 weeks later, with conventional fractionation. Some of these patients became operable. About half of the cases had castration and/or hormone therapy and/or chemotherapy. In the group of patients with T4M0, 59.8% were alive after more than 1 year, and of them, 43.7% had no evidence of disease. These encouraging results suggest that this method be advocated in T4 of the breast because of its rapidity and good tolerance with no significant complications.

  8. Altered thyroxin and retinoid metabolic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin in aryl hydrocarbon receptor-null mice

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Noriko; Yonemoto, Junzo [National Institute for Environmental Studies, Endocrine Disruptors and Dioxin Research Project, Tsukuba (Japan); Miyabara, Yuichi [Shinshu University, Research and Education Center for Inlandwater Environment, Nagano (Japan); Fujii-Kuriyama, Yoshiaki [University of Tsukuba, Center for Tsukuba Advanced Research Alliance, Tsukuba (Japan); Tohyama, Chiharu [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba (Japan)


    To determine whether the disruption of thyroid hormone and retinoid homeostasis that occurs after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can be mediated by the arylhydrocarbon receptor (AhR), pregnant AhR-heterozygous (AhR+/-) mice were administered a single oral dose of 10 {mu}g kg{sup -1} TCDD at gestation day 12.5. Serum and liver were collected on postnatal day 21 from vehicle-treated control or TCDD-treated AhR+/- and AhR-null (AhR-/-) mouse pups. Whereas TCDD exposure resulted in a marked reduction of total thyroxin (TT4) and free T4 (FT4) levels in the serum of AhR+/- mice, TCDD had no effects on AhR-/- mice. Gene expression of UDP-glucuronosyltransferase (UGT)1A6, cytochrome P450 (CYP)1A1, and CYP1A2 in the liver was induced markedly by TCDD in AhR+/- but not AhR-/- mice. Induction of CYP1A1 in response to TCDD was confirmed by immunohistochemical evidence in that CYP1A1 protein was conspicuously localized in the cytoplasm of hepatocytes in the centrilobular region. Levels of retinyl palmitate were greatly reduced in the liver of TCDD-exposed AhR+/- mice, but not in vehicle-treated AhR+/- mice. No effects of TCDD on retinoid levels in the liver were found in AhR-/- mice. We conclude that disruption of thyroid hormone and retinoid homeostasis is mediated entirely via AhR. Induction of UGT1A6 is thought to be responsible at least partly for reduced serum thyroid hormone levels in TCDD-exposed mice. (orig.)

  9. Tweaking the structure to radically change the function: the evolution of transthyretin from 5-hydroxyisourate hydrolase to triiodothyronine distributor to thyroxine distributor.

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    Samantha J. Richardson


    Full Text Available Often, we elucidate evolutionary processes backwards, starting with eutherian mammals and gradually climbing down the evolutionary tree to those species who have survived since long before mammals evolved. This is also true for elucidating the evolution of specific proteins, in this case the protein currently known as transthyretin. Transthyretin (TTR was first described in eutherian mammals and was known as a thyroxine (T4 binding protein. However, mammals are the exception amongst vertebrates in respect to the function of TTR, as in teleost fish, amphibians, reptiles and birds TTR preferentially binds triiodothyronine (T3, which is the active form of thyroid hormone. The TTR gene possibly arose as a duplication of the TLP (TTR-Like Protein gene, around the stage of the agnathans. Some vertebrate species have both the TTR and TLP genes, whilst others have lost the TLP gene. TLP genes have been found in all kingdoms. The TLPs analysed to date do not bind thyroid hormones or their analogues, but are enzymes involved in uric acid metabolism, specifically, they are 5-hydroxyisourate hydrolases. A Salmonella TLP knock-out strain demonstrated that TLP was essential for the bacteria’s survival in the high uric acid environment of the chicken alimentary tract. Many other TLPs are yet to be characterised for their function although several have been confirmed as 5-hydroxyisourate hydrolases. This review describes the evolution of TLP/TTR and how subtle changes in gene structure or amino acid substitution can drastically change the function of this protein, without altering its overall 3D conformation.

  10. Effects of early thyroxine treatment on development and growth at age 10.7 years: follow-up of a randomized placebo-controlled trial in children with Down's syndrome. (United States)

    Marchal, Jan Pieter; Maurice-Stam, Heleen; Ikelaar, Nadine A; Klouwer, Femke C C; Verhorstert, Kim W J; Witteveen, M Emma; Houtzager, Bregje A; Grootenhuis, Martha A; van Trotsenburg, A S Paul


    In 2-year-old children with Down's syndrome (DS), early T4 treatment was found to result in slightly better motor development and growth. This study sought to determine long-term effects of early T4 treatment on development and growth in children with DS with either an elevated or normal neonatal TSH concentration. Patients received a single follow-up visit 8.7 years after a randomized placebo-controlled trial (RCT) comparing T4 and placebo treatment during the first 2 years of life. Dutch Academic Hospital. All children who completed the RCT (N = 181, of 196 randomly assigned children) were invited for the follow-up study. A total of 123 participants enrolled, at a mean age of 10.7 years. T4 or placebo treatment from the neonatal period until 2 years. Primary: mental and motor development. Secondary: communication skills, fine-motor coordination, height, weight, and head circumference (HC). Outcomes were compared between T4- and placebo-treated children, and between treatment groups with either a normal (development, communication skills, or fine-motor coordination did not differ between T4- (N = 64) and placebo-treated children (N = 59). T4-treated children had a larger HC (50.4 vs 49.8 cm, P = .04) and tended to be taller (133.2 vs 131.1 cm, P = .06). These differences were somewhat greater in children with TSH ≥ 5 mIU/L (HC: T4, 50.5 vs placebo, 49.7 cm; P = .01; height: T4, 133.8 vs placebo, 130.8 cm; P = .02), but were not found in children with TSH children with DS does not seem to benefit mental or motor development later in life. However, the positive effect on growth is still measurable, especially in children with an elevated plasma TSH concentration in the neonatal period.

  11. Changes in brain gangliosides of the neotene and metamorphic (thyroxine-induced) newt axolotl (Ambystoma mexicanum). (United States)

    Hilbig, R; Schmitt, M; Rahmann, H


    Qualitative and quantitative changes in the concentration of proteins, sialoglycoproteins and gangliosides and in the composition of gangliosides in the brains of the neotene and the thyroxine-induced metamorphic newt axolotl (Ambystoma mexicanum) were investigated. During metamorphosis two polar gangliosides (GT1b and GQ1b) decreased by about 5% each. On the contrary GD1a increased to 10%. Another developmental trend was a slight increase of two other disialogangliosides (GD1b, GD2). Additionally, incorporation profiles (2-8 days) of 14C-N-Ac-mannosamine, the specific precursor for gangliosides, in the brain of neotene and metamorphic axolotls were followed giving evidence of significant changes in the sialoglycoconjugate metabolism of the central nervous system during metamorphosis of this newt.

  12. Free thyroxine in needle washout after fine needle aspiration biopsy of toxic thyroid nodules. (United States)

    Raikov, Nikolai; Nonchev, Boyan; Chaushev, Borislav; Vjagova, Diyana; Todorov, Svetoslav; Bocheva, Yana; Malceva, Daniela; Vicheva, Snejinka; Raikova, Asyia; Argatska, Antoaneta; Raikov, Miroslav


    The main diagnostic tool for toxic adenomas (TA) is radionuclide imaging indicated in patients with evidence of thyroid nodules in combination with thyrotoxic syndrome. Thyroid ultrasound and fine-needle aspiration biopsy (FNAB) are widely used for the valuation of thyroid masses. There is no literature data concerning the utility of FNAB and related tests for the diagnosis of hyperfunctioning thyroid nodules. The purpose of this study is to determine the levels of free thyroxine (FT4) in the needle washout after FNAB of hot thyroid nodules. The results of our study show that the FT4 levels in needle washout from TA were significantly higher than the surrounding parenchyma and correlated with the hormonal changes in patients with thyroid hyperfunctioning nodules. Further studies on a large number of patients are needed to refine the diagnostic value of this method and evaluate its importance in quantitative risk assessment of thyroid autonomy.

  13. Effect of magnesium sulfate and thyroxine on inflammatory markers in a rat model of hypothyroidism. (United States)

    Abbas, Amr M; Sakr, Hussein F


    Inflammation is a major risk factor for cardiovascular complications. Magnesium sulfate (MgSO4) has anti-inflammatory actions. Therefore we investigated the effects of levothyroxine and MgSO4 on inflammatory markers as C-reactive protein (CRP), interleukin-6, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in hypothyroid rats. Sixty male rats were divided into 6 groups; normal, normal + MgSO4, hypothyroidism, hypothyroidism + levothyroxine, hypothyroidism + MgSO4, and hypothyroidism + levothyroxine + MgSO4. Thyroxine, triiodothyronine, and thyroid-stimulating hormone (TSH), CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 were measured in all rats. Hypothyroidism significantly increased TSH, CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 and decreased triiodothronine and thyroxine. Treatment of hypothyroid rats with levothyroxine or MgSO4 significantly decreased CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1. Combined therapy of hypothyroid rats with levothyroxine and MgSO4 significantly decreased CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 compared with hypothyroid rats either untreated or treated with levothyroxine or MgSO4. This study demonstrates that hypothyroid rats have chronic low grade inflammation, which may account for increased risk of cardiovascular diseases. Combined levothyroxine and MgSO4 is better than levothyroxine or MgSO4 alone in alleviating the chronic low grade inflammatory status and therefore reducing the risk of cardiovascular diseases in hypothyroid animals.

  14. Higher free thyroxine levels are associated with frailty in older men: the Health In Men Study. (United States)

    Yeap, Bu B; Alfonso, Helman; Chubb, Stephen A Paul; Walsh, John P; Hankey, Graeme J; Almeida, Osvaldo P; Flicker, Leon


    Frailty is common in the elderly and predisposes to ill-health. Some symptoms of frailty overlap those of thyroid dysfunction, but it is unclear whether differences in thyroid status influence risk of frailty. We evaluated associations between thyroid status and frailty in older men. Cross-sectional epidemiological study. Community-dwelling men aged 70-89 years. Circulating thyrotropin (TSH) and free thyroxine (FT(4) ) were assayed. Frailty was assessed as ≥3 of the Fatigue, Resistance, Ambulation, Illnesses and Loss (FRAIL) scale's 5 domains: fatigue; resistance (difficulty climbing flight of stairs); ambulation (difficulty walking 100 m); illness (>5); or weight loss (>5%), blinded to hormone results. Of 3943 men, 27 had subclinical hyperthyroidism, 431 subclinical hypothyroidism and 608 were classified as being frail (15·4%). There was an inverse log-linear association of TSH with FT(4). There was no association between TSH and frailty. After adjusting for covariates, men with FT(4) in the highest two quartiles had increased odds of being frail (Q3:Q1, odds ratio [OR] = 1·32, 95% confidence interval [CI] = 1·01-1·73 and Q4:Q1, OR = 1·36, 95% CI = 1·04-1·79, P = 0·010 for trend). Higher FT(4) was associated with fatigue (P = 0·038) and weight loss (P < 0·001). The association between FT(4) and frailty remained significant when the analysis was restricted to euthyroid men. High-normal FT(4) level is an independent predictor of frailty among ageing men. This suggests that even within the euthyroid range, circulating thyroxine may contribute to reduced physical capability. Further studies are needed to clarify the utility of thyroid function testing and the feasibility of preventing or reversing frailty in older men. © 2012 Blackwell Publishing Ltd.

  15. Intensity-modulated radiation therapy for T4 nasopharyngeal carcinoma. Treatment results and locoregional

    Energy Technology Data Exchange (ETDEWEB)

    Chen, J.L.Y.; Tsai, C.L.; Chen, W.Y.; Wang, C.W. [National Taiwan Univ. Hospital, Taipei (China). Div. of Radiation Oncology; Huang, Y.S.; Chen, Y.F. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Medical Imaging; Kuo, S.H. [National Taiwan Univ. Hospital, Taipei (China). Div. of Radiation Oncology; National Taiwan Univ. College of Medicine, Taipei (China). Graduate Inst. of Clinical Medicine; Hong, R.L. [National Taiwan Univ. Hospital, Taipei (China). Div. of Medical Oncology; Ko, J.Y.; Lou, P.J. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Otolaryngology


    Purpose: The purpose of this work was to examine outcomes in patients with T4 nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods and materials: Between 2007 and 2010, 154 patients with nonmetastatic T4 NPC were treated with IMRT to a total dose of 70 Gy in 33-35 fractions. In addition, 97 % of patients received concurrent platinum-based chemotherapy. The median follow-up time was 52.8 months. Results: The rates of 5-year actuarial locoregional control, distant metastasis-free survival, progression free-survival, and overall survival (OS) were 81.2, 72.2, 61.9, and 78.1 %, respectively. A total of 27 patients had locoregional recurrence: 85.2 % in-field failures, 11.1 % marginal failures, and 3.7 % out-of-field failures. Fourteen patients with locoregional recurrence received aggressive treatments, including nasopharyngectomy, neck dissection, or re-irradiation, and the 5-year OS rate tended to be better (61.9 %) compared to those receiving conservative treatment (32.0 %, p = 0.051). In patients treated with 1 course of radiotherapy, grade {>=} 3 toxicities of ototoxicity, neck fibrosis, xerostomia, epistaxis, and radiographic temporal lobe necrosis occurred in 18.2, 9.8, 6.3, 2.1, and 5.6 % of patients, respectively. Increased ototoxicity, osteonecrosis, severe nasal bleeding, and temporal necrosis were observed in patients treated by re-irradiation. Conclusion: IMRT offers good locoregional control in patients with T4 NPC. For patients with locoregional recurrence after definitive radiotherapy, aggressive local treatment may be considered for a better outcome. (orig.)

  16. Specificity of interactions among the DNA-packaging machine components of T4-related bacteriophages. (United States)

    Gao, Song; Rao, Venigalla B


    Tailed bacteriophages use powerful molecular motors to package the viral genome into a preformed capsid. Packaging at a rate of up to ∼2000 bp/s and generating a power density twice that of an automobile engine, the phage T4 motor is the fastest and most powerful reported to date. Central to DNA packaging are dynamic interactions among the packaging components, capsid (gp23), portal (gp20), motor (gp17, large "terminase"), and regulator (gp16, small terminase), leading to precise orchestration of the packaging process, but the mechanisms are poorly understood. Here we analyzed the interactions between small and large terminases of T4-related phages. Our results show that the gp17 packaging ATPase is maximally stimulated by homologous, but not heterologous, gp16. Multiple interaction sites are identified in both gp16 and gp17. The specificity determinants in gp16 are clustered in the diverged N- and C-terminal domains (regions I-III). Swapping of diverged region(s), such as replacing C-terminal RB49 region III with that of T4, switched ATPase stimulation specificity. Two specificity regions, amino acids 37-52 and 290-315, are identified in or near the gp17-ATPase "transmission" subdomain II. gp16 binding at these sites might cause a conformational change positioning the ATPase-coupling residues into the catalytic pocket, triggering ATP hydrolysis. These results lead to a model in which multiple weak interactions between motor and regulator allow dynamic assembly and disassembly of various packaging complexes, depending on the functional state of the packaging machine. This might be a general mechanism for regulation of the phage packaging machine and other complex molecular machines.

  17. Oncological outcomes following radical prostatectomy for patients with pT4 prostate cancer

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    Dharam Kaushik

    Full Text Available ABSTRACT Objectives: Radical prostatectomy (RP for locally advanced prostate cancer may reduce the risk of metastasis and cancer-specific death. Herein, we evaluated the outcomes for patients with pT4 disease treated with RP. Materials and methods: Among 19,800 men treated with RP at Mayo Clinic from 1987 to 2010, 87 were found to have pT4 tumors. Biochemical recurrence (BCR-free survival, systemic progression (SP free survival and overall survival (OS were estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards regression models were used to assess the association of clinic-pathological features with outcome. Results: Median follow-up was 9.8 years (IQR 3.6, 13.4. Of the 87 patients, 50 (57.5% were diagnosed with BCR, 30 (34.5% developed SP, and 38 (43.7% died, with 11 (12.6% dying of prostate cancer. Adjuvant androgen deprivation therapy was administered to 77 men, while 32 received adjuvant external beam radiation therapy. Ten-year BCR-free survival, SP-free survival, and OS was 37%, 64%, and 70% respectively. On multivariate analysis, the presence of positive lymph nodes was marginally significantly associated with patients' risk of BCR (HR: 1.94; p=0.05, while both positive lymph nodes (HR 2.96; p=0.02 and high pathologic Gleason score (HR 1.95; p=0.03 were associated with SP. Conclusions: Patients with pT4 disease may experience long-term survival following RP, and as such, when technically feasible, surgical resection should be considered in the multimodal treatment approach to these men.

  18. Evidence that the heterogeneity of a T4 population is the result of heritable traits.

    Directory of Open Access Journals (Sweden)

    Zachary J Storms

    Full Text Available Many bacteriophage populations display heterogeneity in their adsorption characteristics; a portion of the phage population remains free in solution throughout adsorption experiments (residual fraction. This residual fraction generally constitutes a minority of phages that exhibit significantly slower adsorption kinetics than the main phage stock (main fraction. While this phenomenon is likely the result of evolutionary driving forces, the present study demonstrates that the residual fraction is not always the result of phenotypic variations within a single genotype, as is generally thought. Experiments with phage T4 showed that two subgroups with distinct adsorption traits that were passed on to their progeny could be isolated from the original phage stock. Sequencing of genes involved in adsorption revealed two point mutations in gene 37 of residual fraction isolates, which resulted in modifications to the long tail-fiber, the organelle of attachment and host cell recognition. Adsorption studies consistently showed that T4 phage stocks amplified from residual fraction isolates had significantly lower adsorption efficiencies than those amplified from main fractions. The conducted experiments provide convincing evidence that the observed heterogeneity in T4 adsorption behavior is the result of conserved mutations to the phage genome and is not exclusively the result of phenotypic variations within the population. While it is believed high mutation rates exist to hasten phage adaptation, this study shows that this bet hedging strategy can also, in the short term, inadvertently handicap the phage's adsorption capabilities to a given host under normal infection conditions, resulting in the residual fraction observed in adsorption experiments.

  19. Purification of phage display-modified bacteriophage T4 by affinity chromatography

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    Figura Grzegorz


    Full Text Available Abstract Background Affinity chromatography is one of the most efficient protein purification strategies. This technique comprises a one-step procedure with a purification level in the order of several thousand-fold, adaptable for various proteins, differentiated in their size, shape, charge, and other properties. The aim of this work was to verify the possibility of applying affinity chromatography in bacteriophage purification, with the perspective of therapeutic purposes. T4 is a large, icosahedral phage that may serve as an efficient display platform for foreign peptides or proteins. Here we propose a new method of T4 phage purification by affinity chromatography after its modification with affinity tags (GST and Histag by in vivo phage display. As any permanent introduction of extraneous DNA into a phage genome is strongly unfavourable for medical purposes, integration of foreign motifs with the phage genome was not applied. The phage was propagated in bacteria expressing fusions of the phage protein Hoc with affinity tags from bacterial plasmids, independently from the phage expression system. Results Elution profiles of phages modified with the specific affinity motifs (compared to non-specific phages document their binding to the affinity resins and effective elution with standard competitive agents. Non-specific binding was also observed, but was 102-105 times weaker than the specific one. GST-modified bacteriophages were also effectively released from glutathione Sepharose by proteolytic cleavage. The possibility of proteolytic release was designed at the stage of expression vector construction. Decrease in LPS content in phage preparations was dependent on the washing intensity; intensive washing resulted in preparations of 11-40 EU/ml. Conclusions Affinity tags can be successfully incorporated into the T4 phage capsid by the in vivo phage display technique and they strongly elevate bacteriophage affinity to a specific resin. Affinity

  20. [Effect of T4 endoscopic thoracic sympathicotomy on life quality in patients with primary palmar hyperhidrosis]. (United States)

    Xiao, Peng; Liu, Aizhong; Liu, Wenliang



  1. Template-directed ligation of tethered mononucleotides by t4 DNA ligase for kinase ribozyme selection.

    Directory of Open Access Journals (Sweden)

    David G Nickens

    Full Text Available BACKGROUND: In vitro selection of kinase ribozymes for small molecule metabolites, such as free nucleosides, will require partition systems that discriminate active from inactive RNA species. While nucleic acid catalysis of phosphoryl transfer is well established for phosphorylation of 5' or 2' OH of oligonucleotide substrates, phosphorylation of diffusible small molecules has not been demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: This study demonstrates the ability of T4 DNA ligase to capture RNA strands in which a tethered monodeoxynucleoside has acquired a 5' phosphate. The ligation reaction therefore mimics the partition step of a selection for nucleoside kinase (deoxyribozymes. Ligation with tethered substrates was considerably slower than with nicked, fully duplex DNA, even though the deoxynucleotides at the ligation junction were Watson-Crick base paired in the tethered substrate. Ligation increased markedly when the bridging template strand contained unpaired spacer nucleotides across from the flexible tether, according to the trends: A(2>A(1>A(3>A(4>A(0>A(6>A(8>A(10 and T(2>T(3>T(4>T(6 approximately T(1>T(8>T(10. Bridging T's generally gave higher yield of ligated product than bridging A's. ATP concentrations above 33 microM accumulated adenylated intermediate and decreased yields of the gap-sealed product, likely due to re-adenylation of dissociated enzyme. Under optimized conditions, T4 DNA ligase efficiently (>90% joined a correctly paired, or TratioG wobble-paired, substrate on the 3' side of the ligation junction while discriminating approximately 100-fold against most mispaired substrates. Tethered dC and dG gave the highest ligation rates and yields, followed by tethered deoxyinosine (dI and dT, with the slowest reactions for tethered dA. The same kinetic trends were observed in ligase-mediated capture in complex reaction mixtures with multiple substrates. The "universal" analog 5-nitroindole (dNI did not support ligation when

  2. Pathology of advanced buccal mucosa cancer involving masticator space (T4b

    Directory of Open Access Journals (Sweden)

    N P Trivedi


    Full Text Available BACKGROUND: Buccal mucosa cancer involving masticator space is classified as very advanced local disease (T4b. The local recurrence rate is very high due to poor understanding of the extent of tumor spread in masticator space and technically difficult surgical clearance. The objective of this study is to understand the extent of tumor spread in masticator space to form basis for appropriate surgical resection. MATERIALS AND METHODS: All consecutive patients with T4b-buccal cancer underwent compartment resection, with complete anatomical removal of involved soft-tissue structures. Specimens were systematically studied to understand the extent of invasion of various structures. The findings of clinical history, imaging and pathologic evaluation were compared and the results were evaluated. RESULTS: A total of 45 patients with advanced buccal cancer (T4b were included in this study. The skin, mandible and lymph nodes were involved in 30, 24 and 17 cases respectively. The pterygoid muscles were involved in 34 cases (medial-pterygoid in 12 and both pterygoids in 22 cases and masseter-muscle in 32 cases. Average distance for soft-tissue margins after compartment surgery was 2 cm and the margins were positive in 3 cases. The group with involvement of medial pterygoid muscle had safest margin with compartment surgery while it was also possible to achieve negative margins for group involving lateral pterygoid muscle and plates.The involvement of pterygomaxillary fissure was area of concern and margin was positive in 2 cases with one patient developing local recurrence with intracranial extension. At 21 months median follow-up (13-35 months, 38 patients were alive without disease while two developed local recurrence at the skull base.CONCLUSIONS: T4b buccal cancers have significant soft-tissue involvement in the masticator space. En bloc removal of all soft-tissues in masticator space is advocated to remove tumor contained within space. The compartment

  3. Constructive Tensorial Group Field Theory II: The $U(1)-T^4_4$ Model

    CERN Document Server

    Lahoche, Vincent


    In this paper we continue our program of non-pertubative constructions of tensorial group field theories (TGFT). We prove analyticity and Borel summability in a suitable domain of the coupling constant of the simplest super-renormalizable TGFT which contains some ultraviolet divergencies, namely the color-symmetric quartic melonic rank-four model with Abelian $U(1)$ gauge invariance, nicknamed $U(1)-T^4_4$. We use a multiscale loop vertex expansion. It is an extension of the loop vertex expansion (the basic constructive technique for non-local theories) which is required for theories that involve non-trivial renormalization.

  4. On symmetries of N=(4,4) sigma models on T^4

    CERN Document Server

    Volpato, Roberto


    Motivated by an analogous result for K3 models, we classify all groups of symmetries of non-linear sigma models on a torus T^4 that preserve the N=(4,4) superconformal algebra. The resulting symmetry groups are isomorphic to certain subgroups of the Weyl group of E8, that plays a role similar to the Conway group for the case of K3 models. Our analysis heavily relies on the triality automorphism of the T-duality group SO(4,4,Z). As a byproduct of our results, we discover new explicit descriptions of K3 models as asymmetric orbifolds of torus CFTs.

  5. 5T4 Oncotrophoblast Glycoprotein: Janus Molecule in Life and a Novel Potential Target against Tumors

    Institute of Scientific and Technical Information of China (English)

    Yu Zhao; Yuxia Wang


    5T4 oncotrophoblast glycoprotein is a transmembrane protein expressed on the embryonic tissue and various malignant tumor cell surfaces. It plays a vital role in the multiple biological and pathological processes including massive cellular migration during the embryogenesis, cell invasion associated with implantation, and neoplastic metastasis in the progression of tumorigenesis. Its restricted profile of expression stratifies criteria of tumorassociated antigen and makes it a new promising candidate for immunotherapy for cancer. Hence, illustrating this molecular function is necessary for discovering the principle of the tumor diffusion and aggravation and is helpful for developing novel and effective strategies of cancer therapy.

  6. Human Volunteers Receiving Escherichia coli Phage T4 Orally: a Safety Test of Phage Therapy


    Bruttin, Anne; Brüssow, Harald


    Fifteen healthy adult volunteers received in their drinking water a lower Escherichia coli phage T4 dose (103 PFU/ml), a higher phage dose (105 PFU/ml), and placebo. Fecal coliphage was detected in a dose-dependent way in volunteers orally exposed to phage. All volunteers receiving the higher phage dose showed fecal phage 1 day after exposure; this prevalence was only 50% in subjects receiving the lower phage dose. No fecal phage was detectable a week after a 2-day course of oral phage applic...

  7. Quantification of thyroxine by the selective photoluminescence quenching of L-cysteine–ZnS quantum dots in aqueous solution containing hexadecyltrimethylammonium bromide

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Sarzamin; Carneiro, Leonardo S.A. [Chemistry Department, Pontifícia Universidade Católica do Rio de Janeiro, 22451-900 Rio de Janeiro-RJ (Brazil); Romani, Eric C.; Larrudé, Dunieskys G. [Physics Department, Pontifícia Universidade Católica do Rio de Janeiro, 22451-900, Rio de Janeiro-RJ (Brazil); Aucelio, Ricardo Q., E-mail: [Chemistry Department, Pontifícia Universidade Católica do Rio de Janeiro, 22451-900 Rio de Janeiro-RJ (Brazil)


    The determination of L-thyroxine is proposed based on the photoluminescence quenching effect caused on the L-cysteine modified ZnS quantum dots (L-cysteine ZnS QDs) aqueous dispersion. Under optimum conditions, the analytical response followed a Stern–Volmer model and the experimental conditions were adjusted to enable a robust and reproducible photoluminescence signal. The linear response observed in the quantum dots aqueous dispersion covered the L-thyroxine concentration from the LOQ (2.0×10{sup −8} mol L{sup −1}) to 4.0×10{sup −6} mol L{sup −1}. The approach was tested in the determination of L-thyroxine in pharmaceutical formulations used to treat patients with thyroid gland disorder. The percent recoveries in controlled samples were between 93.3 and 103%. Analyte fortified saliva was also evaluated as a possible sample for L-thyroxine monitoring of a patient under treatment. It was identified a static type of photoluminescence quenching caused by L-thyroxine. - Highlights: • L-cysteine ZnS QDs were used as a photoluminescent probe to detect L-thyroxine. • Intensity of probe decreases following a Stern–Volmer model. • The method can detect down ng L{sup −1} levels of L-thyroxine in the probe dispersion. • Method was used to determinate of L-thyroxine in saliva and in pharmaceuticals. • Mechanism of interaction between L-thyroxine and quantum dots was studied.

  8. T4噬菌体32蛋白的表达、纯化及鉴定%Expression,Purification and Identification of T4 Bacteriophage 32 Protein

    Institute of Scientific and Technical Information of China (English)

    胡子有; 曾勇; 吴炳义


    Objective To construct the prokaryotic expression plasmid T4-32-pET28b containing T4 bacteriophage 32 protein and to express, purify, and identify the target protein. Methods The full length DNA fragment of 32 protein was amplified from T4 bacteriophage genomic DNA by PCR using high fidelity DNA polymerase. And the PCR product was inserted into the prokaryotic expression plasmid pET28b in oriented cloning. Then, T4-32-pET28b was transformed into BL21 ( DE3) and the expression of the target protein was induced with 1. 0 mmol/L IPTG at 37℃. T4-32 protein was purified from crude extracts using Ni immobilized metal ion affinity chromatography and desalted using Sephadex G-25. The purified T4-32 protein was detected by assays for contamination of bacterial genomic DNA and nucleases. The ability of T4-32 binding single strand DNA was also determined in agarose electrophoresis. Results Restriction enzyme digestion and sequencing showed that the sequence of T4-32 in T4-32-pET28b was correct. The T4-32 protein was successfully expressed in BL21 ( DE3) and highly purified. Conclusion The prokaryotic expression vector T4-32-pET28b, which could be used for expressing large amounts of purified T4-32 protein, was successfully constructed.%目的 构建T4噬菌体32蛋白的原核表达质粒T4-32-pET28b,并表达、纯化和鉴定重组目的 蛋白.方法以T4噬菌体DNA 基因组为模板,PCR扩增得到32蛋白基因片段,定向克隆到原核表达载体pET28b中,转化入大肠埃希菌BL21(DE3)中,用IPTG诱导表达目的 蛋白,然后进行镍柱纯化和G-25脱盐,获得纯化目的 蛋白,并进行核酸酶和细菌基因组污染检测及结合DNA单链能力检测.结果 构建的T4-32-pET28b质粒经酶切及测序鉴定正确,在BL21(DE3)成功表达了T4-32蛋白,经镍柱和脱盐纯化获得了高纯度的目的 蛋白.结论 成功构建了T4噬菌体32蛋白的原核表达载体T4- 32-pET28b,并实现高表达和纯化了目的 表达产物.

  9. Acanthamoeba genotypes T3 and T4 as causative agents of amoebic keratitis in Mexico. (United States)

    Omaña-Molina, Maritza; Vanzzini-Zago, Virginia; Hernandez-Martinez, Dolores; Gonzalez-Robles, Arturo; Salazar-Villatoro, Lizbeth; Ramirez-Flores, Elizabeth; Oregon-Miranda, Eric; Lorenzo-Morales, Jacob; Martinez-Palomo, Adolfo


    Free-living amoebae (FLA) are widely distributed worldwide. Some genera included in this group act as opportunistic pathogens causing fatal encephalitis and Acanthamoeba keratitis (AK), a sight-threatening infection of the cornea associated with the use of soft contact lenses that could even end in blindness if an early diagnosis and treatment are not achieved. Furthermore, the numbers of AK cases keep rising worldwide mainly due to an increase of contact lens wearers and lack of hygiene in the maintenance of lenses and their cases. In Mexico, no cases of AK have been described so far although the isolation of other pathogenic FLA such as Naegleria fowleri and Balamuthia mandrillaris from both clinical and environmental sources has been reported. The present study reports two cases of Acanthamoeba keratitis diagnosed in two patients admitted to the Hospital "Luis Sánchez Bulnes" for Blindness Prevention in Mexico City, Mexico. Corneal scrapes and contact lenses were checked for the presence of Acanthamoeba strains in both patients. Strains were axenized after initial isolation to classify at the genotype level. After sequencing the diagnostic fragment 3 (DF3) region located on the 18S ribosomal DNA (rDNA) gene of Acanthamoeba, genotype T3 and genotype T4 were identified in clinical case 1 and 2, respectively. To our knowledge, these are the first reported cases of AK in Mexico in the literature and the first description of Acanthamoeba genotypes T3 and T4 as causative agents of amoebic infection.

  10. Acanthamoeba T4, T5 and T11 isolated from mineral water bottles in southern Brazil. (United States)

    Maschio, Vinicius José; Chies, Fernanda; Carlesso, Ana Maris; Carvalho, Amanda; Rosa, Sayonara Peixoto; Van Der Sand, Sueli Teresinha; Rott, Marilise Brittes


    Acanthamoeba is a protist potential pathogen, capable of causing a blinding keratitis in contact lens wearers and disseminated infection, leading to granulomatous amebic encephalitis in immunocompromised individuals. This amoeba is a ubiquitous organism that has been isolated from various domestic water systems, such as cooling towers and hospital water networks. The objective of this work was to investigate the presence of Acanthamoeba in mineral water bottles marketed in Porto Alegre, southern Brazil. Positive samples were further classified at the genotype level after sequencing the ASA.S1 region of 18S rDNA gene. Six of the eight isolates belonged to T5 genotype, one to T4 genotype, and one was T11. Several genotypes have been reported worldwide as causative of pathologies in humans, including genotypes T4, T5 and T11. Overall, the widespread distribution of potentially pathogenic Acanthamoeba strains in the studied source demands more awareness within the public and health professionals, because this pathogen is emerging as a risk for human health worldwide.

  11. Mini Transsternal Approach to the Anterior High Thoracic Spine (T1–T4 Vertebrae

    Directory of Open Access Journals (Sweden)

    Christian Brogna


    Full Text Available Purpose. The anterior high thoracic spine is one of the most complex segments to be accessed surgically due to anatomical constraints and transitional characteristics. We describe in detail the mini transsternal approach to metastatic, infective, traumatic, and degenerative pathologies of T1 to T4 vertebral bodies. We analyse our surgical series, indications, and outcomes. Methods. Over a 5-year period 18 consecutive patients with thoracic myelopathy due to metastatic, infective, traumatic, and degenerative pathologies with T1 to T4 vertebral bodies involvement received a mini transsternal approach with intraoperative monitoring. Frankel scoring system was used to grade the neurological status. Results. Mean follow-up was 40 months. 78% patients improved in Frankel grade after surgery and 22% patients remained unchanged. Average operation time was 210 minutes. There were no intraoperative complications. One patient developed postoperative pneumonia successfully treated with antibiotics. Conclusion. The mini transsternal is a safe approach for infective, metastatic, traumatic, and degenerative lesions affecting the anterior high thoracic spine and the only one allowing an early and direct visualisation of the anterior theca. This approach overcomes the anatomical constraints of this region and provides adequate room for optimal reconstruction and preservation of spinal alignment in the cervicothoracic transition zone with good functional patient outcomes.

  12. Experimental Study of Stationary Shoulder Friction Stir Welded 7N01-T4 Aluminum Alloy (United States)

    Ji, S. D.; Meng, X. C.; Li, Z. W.; Ma, L.; Gao, S. S.


    Stationary shoulder friction stir welding (SSFSW) was successfully used to weld 7N01-T4 aluminum alloy with the thickness of 4 mm. Effects of welding speed on formations, microstructures, and mechanical properties of SSFSW joint were investigated in detail. Under a constant rotational velocity of 2000 rpm, defect-free joints with smooth surface and small flashes are attained using welding speeds of 20 and 30 mm/min. Macrostructure of nugget zone in cross section presents kettle shape. For 7N01-T4 aluminum alloy with low thermal conductivity, decreasing welding speed is beneficial to surface formation of joint. With the increase of welding speed, mechanical properties of joints firstly increase and then decrease. When the welding speed is 30 mm/min, the tensile strength and elongation of joint reach the maximum values of 379 MPa and 7.9%, equivalent to 84.2 and 52% of base material, respectively. Fracture surface morphology exhibits typical ductile fracture. In addition, the minimum hardness value of joint appears in the heat affected zone.

  13. Microstructure and mechanical properties of friction stir welded thin sheets of 2024-T4 aluminum alloy

    Institute of Scientific and Technical Information of China (English)

    LI Lian; TONG Jian-hua; WAN Fa-rong; LONG Yi


    Friction stir welding (FSW) is a new and promising welding processing that can produce low-cost and high-quality joints of aluminum alloys. 1 mm thick sheets of 2024-T4 aluminum alloys which are always used as building and decorating materials were welded by FSW. The microstrueture and mechanical properties of friction stir welded 1 mm thick sheets of 2024-T4 aluminum alloy were studied. It was found that the thinner the 2024 aluminum alloy, the larger the FSW technological parameters field. The grains size of weld nugget zone (WNZ) is approximately 10 times smaller than that of the parent material, but the second phase in the material is not refined apparently in the welding. The FS welded joints have about 40% higher yield strength than the parent material,but the elongation of FS welded joints is under about 50% of the parent material. The electron backscattered diffraction (EBSD)results show that there are much more low angle boundaries (LAB) in WNZ than that in parent material, which indicates that FSW causes a number of sub-grain structures in WNZ, and this is also the reason of the increase of yield strength and Vickers hardness of the welded joint.

  14. The effect of bacteriophages T4 and HAP1 on in vitro melanoma migration

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    Boratyński Janusz


    Full Text Available Abstract Background The antibacterial activity of bacteriophages has been described rather well. However, knowledge about the direct interactions of bacteriophages with mammalian organisms and their other, i.e. non-antibacterial, activities in mammalian systems is quite scarce. It must be emphasised that bacteriophages are natural parasites of bacteria, which in turn are parasites or symbionts of mammals (including humans. Bacteriophages are constantly present in mammalian bodies and the environment in great amounts. On the other hand, the perspective of the possible use of bacteriophage preparations for antibacterial therapies in cancer patients generates a substantial need to investigate the effects of phages on cancer processes. Results In these studies the migration of human and mouse melanoma on fibronectin was inhibited by purified T4 and HAP1 bacteriophage preparations. The migration of human melanoma was also inhibited by the HAP1 phage preparation on matrigel. No response of either melanoma cell line to lipopolysaccharide was observed. Therefore the effect of the phage preparations cannot be attributed to lipopolysaccharide. No differences in the effects of T4 and HAP1 on melanoma migration were observed. Conclusion We believe that these observations are of importance for any further attempts to use bacteriophage preparations in antibacterial treatment. The risk of antibiotic-resistant hospital infections strongly affects cancer patients and these results suggest the possibility of beneficial phage treatment. We also believe that they will contribute to the general understanding of bacteriophage biology, as bacteriophages, extremely ubiquitous entities, are in permanent contact with human organisms.

  15. Analysis on virus resistance and fruit quality for T4 generation of transgenic papaya

    Institute of Scientific and Technical Information of China (English)

    WEI Xiangdong; LAN Congyu; LU Zhijing; YE Changming


    Molecular biological characterization,fruit characters,and nutrients were analyzed for T4 generation of transgenic papaya.All transgenic papaya plants with the mutated replicase (RP) gene from papaya ringspot virus (PRSV) showed high resistance or immunity against PRSV in the field.The RP transgene can be steadily inherited to,and expressed at RNA level,the progenies.The growth characteristics of transgenic papaya were much better than nontransgenic papaya in the field.The non-transgenic papaya seedlings began to show typical symptoms caused by PRSV after being inoculated with PRSV.They died quickly and never grew to produce fruit.The adult trees developed yellow leaves and produced smaller fruits and were doomed to a slow death after some time,while most oftransgenic papaya plants (about 91.8%) did not show any symptoms caused by PRSV,and produced more,bigger,and high quality fruits.Compared with non-transgenic plants,the fresh fruit length of T4 generation of transgenic papaya increased 2.6%-5%,and the diameter decreased 0.6%-1.5%.The flesh thickness of fresh fruit increased 12%-15%,which made it fitter for eating.Although the fresh fruit quality changed,there was no significant difference between transgenic and non-transgenic papaya.The quality characteristics of dry fruit including the contents of water,lipid,N,protein,reduced sugar,vitamin A,vitamin C,and carotene in the T4 generation of transgenic papaya were all the same as their non-transgenic parents.This means that transgenic plants and non-transgenic plants are substantially equivalent,and the transgene has no effect on dry fruit quality.In this study,we found that vitamin A and vitamin C in red-fleshed papaya were 1.4-1.8 and 1.78-2.07 times more than the yellow-fleshed ones,respectively,while N and protein were only 84.2%-92.1% and 82.1%-98.9% of the yellow-fleshed ones.

  16. Modelling T4 cell count as a marker of HIV progression in the absence of any defence mechanism

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    VSS Yadavalli


    Full Text Available The T4 cell count, which is considered one of the markers of disease progression in an HIV infected individual, is modelled in this paper. The World Health Organisation has recently advocated that countries encourage HIV infected individuals to commence antiretroviral treatments once their T4 cell count drops below 350 cells per ml of blood (this threshold was formerly 200 cells per ml of blood. This recommendation is made because when the T4 cell count is low, the T4 cells are unable to mount an effective immune response against antigens and any such foreign matters in the body, and consequently the individual becomes susceptible to opportunistic infections and lymphomas. A stochastic catastrophe model is developed in this paper to obtain the mean, variance and covariance of the uninfected, infected and lysed T4 cells. The amount of toxin produced in an HIV infected person from the time of infection to a later time may also be obtained from the model. Numerical illustrations of the correlation structures between uninfected and infected T4 cells, and between the infected and lysed T4 cells are also presented.

  17. Use of adenylate kinase as a solubility tag for high level expression of T4 DNA ligase in Escherichia coli. (United States)

    Liu, Xinxin; Huang, Anliang; Luo, Dan; Liu, Haipeng; Han, Huzi; Xu, Yang; Liang, Peng


    The discovery of T4 DNA ligase in 1960s was pivotal in the spread of molecular biotechnology. The enzyme has become ubiquitous for recombinant DNA routinely practiced in biomedical research around the globe. Great efforts have been made to express and purify T4 DNA ligase to meet the world demand, yet over-expression of soluble T4 DNA ligase in E. coli has been difficult. Here we explore the use of adenylate kinase to enhance T4 DNA ligase expression and its downstream purification. E.coli adenylate kinase, which can be expressed in active form at high level, was fused to the N-terminus of T4 DNA ligase. The resulting His-tagged AK-T4 DNA ligase fusion protein was greatly over-expressed in E. coli, and readily purified to near homogeneity via two purification steps consisting of Blue Sepharose and Ni-NTA chromatography. The purified AK-T4 DNA ligase not only is fully active for DNA ligation, but also can use ADP in addition to ATP as energy source since adenylate kinase converts ADP to ATP and AMP. Thus adenylate kinase may be used as a solubility tag to facilitate recombinant protein expression as well as their downstream purification.

  18. Atomic force microscopy images of T4 bacteriophages on silicon substrates

    Energy Technology Data Exchange (ETDEWEB)

    Kolbe, W.F.; Ogletree, D.F.; Salmeron, M.B.


    A new atomic force microscope incorporating microfabricated cantilevers and employing laser beam deflection for force detection has been constructed and is being applied to studied of biological material. In this study, T4 bacteriophage virus particles were deposited from solution onto electronic grade flat silicon wafers and imaged in air with the microscope. Microliter droplets of the solution were deposited and either allowed to dry or removed with blotting paper. The images show both isolated viruses and aggregates of various sizes. The external structure as well as strands believed to be DNA streaming out of the virus could be observed. The construction of the microscope and its performance are also described. 19 refs., 4 figs.

  19. Carbon loss during irradiation of T4 bacteriophages and E. coli bacteria in electron microscopes

    Energy Technology Data Exchange (ETDEWEB)

    Dubochet, J.


    The loss of /sup 14/C due to electron irradiation has been measured on labeled T4 bacteriophages and E. coli bacteria under conditions relevant for practical electron microscopy for fixed and scanning beam exposure. During irradiation, the remaining material became less and less sensitive to further carbon loss. Surface migration of molecular fragments and adsorbed molecules is involved in the process of beam damage. In CTEM under normal working conditions, the parameters on which the carbon loss depends cannot all be controlled. There is no perceptible carbon loss when the irradiation is made at liquid helium temperature. The material surrounding the biological object, the way in which the electron dose is given to the specimen, and the vacuum conditions in the specimen chamber influence the process. We conclude that secondary reactions of molecular fragments formed after inelastic scattering events are of importance and depend on the layer of molecules adsorbed onto the surface of the specimen. (auth)

  20. Study of the transfer RNAs coded by T2, T4, and T6 bacteriophages

    Energy Technology Data Exchange (ETDEWEB)

    Desai, S.M.; Weiss, S.B.


    T2,T4, and T6 bacteriophage tRNAs coding for arginine, leucine, proline, isoleucine, and glycine were isolated under conditions of short term and long term infection of Escherchia coli B cells. The corresponding phage tRNA species were examined for sequence homology by RNA.DNA hybridization analysis and by their relative behavior on reversed phase chromatography. The results indicate that all three T-even phages code for similar tRNA species; however, some tRNA species are homologous, others are not, and not all of the same tRNA species are coded by each bacteriophage. Reversed phase chromatography showed the presence of isoacceptor tRNAs for each phage aminoacyl-tRNA species. Pulse-chase experiments for (/sup 32/P)tRNA/sup Gly/ suggest that the multiple isoacceptor species observed derive from the intracellular modification of a single tRNA/sup Gly/ gene product.

  1. Bacteriophage T4 development in Escherichia coli is growth rate dependent. (United States)

    Rabinovitch, Avinoam; Fishov, Itzhak; Hadas, Hilla; Einav, Monica; Zaritsky, Arieh


    Three independent parameters (eclipse and latent periods, and rate of ripening during the rise period) are essential and sufficient to describe bacteriophage development in its bacterial host. A general model to describe the classical "one-step growth" experiment [Rabinovitch et al. (1999a) J. Bacteriol.181, 1687-1683] allowed their calculations from experimental results obtained with T4 in Escherichia coli B/r under different growth conditions [Hadas et al. (1997) Microbiology143, 179-185]. It is found that all three parameters could be described by their dependence solely on the culture doubling time tau before infection. Their functional dependence on tau, derived by a best-fit analysis, was used to calculate burst size values. The latter agree well with the experimental results. The dependence of the derived parameters on growth conditions can be used to predict phage development under other experimental manipulations.

  2. Study of residual stresses in tailor rolled blanked Al5J32-T4 sheets

    Institute of Scientific and Technical Information of China (English)

    KIM Dongok; KIM Jinpyeong; LEE Yong; KWAK Heeman; RYU Yongmun; HAN Beomsuck


    Several automotive parts such as door panels have been manufactured by using load-adapted blanks for crash optimization and weight minimization.Recently, Tailor Rolled Blanks (TRB) has been introduced to remove the disadvantages of a welding process which was used in joining panel components.TRB offers better structural design capabilities due to the seamless transitions on the panels with different thicknesses.In spite of the advantages of the process, TRB leaves internal stresses in the panel.This residual stresses lower the formability of Tailor Rolled Blanked (TRBed) parts and cause cracks near severe curvature during subsequent forming processes.In this research, the residual stresses of TRBed Al5J32-T4 sheets were studied by X-ray stress analysis, and also microstructure was observed along the rolling direction.In addition, heat treatment was done after TRB process in order to compare the residual stresses to that of the TRBed sheets before the heat treatment.

  3. Isolation of Acanthamoeba Genotype T4 from a Non-Contact Lens Wearer from the Philippines (United States)

    Buerano, Corazon C.; Trinidad, Abigail D.; Fajardo, Lindsay Sydney N.; Cua, Irwin Y.; Baclig, Michael O.; Natividad, Filipinas F.


    We report the case of a 76-year old Filipino male who presented with pain, redness, and blurring of vision of the right eye. Corneal scraping was done and sent to the St. Luke’s Research and Biotechnology Group for detection and identification of the infectious agent. Morphological detection was performed by allowing the organism from the scraping to grow in 1.5% non-nutrient agar plate with heat-killed E. coli. Trophozoites with acanthopodia and double-walled cysts characteristic of Acanthamoeba were observed within the first and second week of observations, respectively. Molecular identification of the amoebae at the genus level based on the presence of Acanthamoeba-specific amplimer S1, ASA.S1 confirmed the morphological identification. Genotyping through sequence revealed that the organism belonged to T4, which is the genotype commonly present in the eye of keratitis patients. PMID:25589879


    Institute of Scientific and Technical Information of China (English)

    S.X. Lü; J.C. Yan; W.G. Li; S.Q. Yang


    e thermal model of FSW based on the thermal elastic-plastic finite element method, and the transient temperature distribution of FS welded joints of 2024-T4 Al was simulated by using this model, which provides useful information for the investigation of FSW process. Simulation results show that the temperature distribution of the weld gradually decreases toward periphery in a radiate format, whose center is the probe, and the highest temperature in the weld can reach about 400℃. The initial terminal of the weld is a zone, in which the temperature gradient is great, and defects of the welding are easily produced in this zone. Temperature change at the end of the welded joint is as layer variation, the local serious defects are not easy to produce in this zone.

  5. CCD photometry of active Centaur 166P/2001 T4 (NEAT) (United States)

    Shi, J. C.; Ma, Y. H.


    To study the secular evolution of the activity of Centaur 166P/2001 T4 (Near Earth Asteroid Tracking, NEAT) and its physical properties, we present the results of optical observations of the Centaur taken on 2009 March 29 with the Keck 10-m telescope located atop Mauna Kea, Hawaii. It was still active at rh = 11.9 au post-perihelion. An upper limit of the nucleus radius of aN < 14.32 km is derived. The colour index is B - R = 1.59 ± 0.05. The Afρ value is measured to be 288 ± 19 cm and the corresponding dust production rate is 252 kg s-1. Finally, a possible mechanism of activity is discussed.

  6. Themo-mechanical and microstructural modeling of friction stir welding of 6111-T4 aluminum alloys (United States)

    Kim, Ji Hoon; Barlat, Frédéric; Kim, Chongmin; Chung, Kwansoo


    Plastic deformation and thermal history as well as microstructure evolution of friction stir welded 6111-T4 aluminum alloys were numerically simulated. Material and heat flow during friction stir welding were calculated considering the momentum balance equation and energy balance equation under the steady state condition. Based on the calculated temperature history, the coupled nucleation, growth, and coarsening of precipitates were simulated using microstructural modeling, as proposed by Myhr et al. [7,8]. Finally, the distribution of precipitates was used to calculate the mechanical properties of the weld zone, particularly the yield stress, based on the dislocation theory. The results compared well with the measurements, suggesting that the method can be applicable to predict yield stress.

  7. Perspectives from NHLBI Global Health Think Tank Meeting for Late Stage (T4) Translation Research. (United States)

    Engelgau, Michael M; Peprah, Emmanuel; Sampson, Uchechukwu K A; Mishoe, Helena; Benjamin, Ivor J; Douglas, Pamela S; Hochman, Judith S; Ridker, Paul M; Brandes, Neal; Checkley, William; El-Saharty, Sameh; Ezzati, Majid; Hennis, Anselm; Jiang, Lixin; Krumholz, Harlan M; Lamourelle, Gabrielle; Makani, Julie; Narayan, K M Venkat; Ohene-Frempong, Kwaku; Straus, Sharon E; Stuckler, David; Chambers, David A; Belis, Deshirée; Bennett, Glen C; Boyington, Josephine E; Creazzo, Tony L; de Jesus, Janet M; Krishnamurti, Chitra; Lowden, Mia R; Punturieri, Antonello; Shero, Susan T; Young, Neal S; Zou, Shimian; Mensah, George A


    Almost three-quarters (74%) of all the noncommunicable disease burden is found within low- and middle-income countries. In September 2014, the National Heart, Lung, and Blood Institute held a Global Health Think Tank meeting to obtain expert advice and recommendations for addressing compelling scientific questions for late stage (T4) research-research that studies implementation strategies for proven effective interventions-to inform and guide the National Heart, Lung, and Blood Institute's global health research and training efforts. Major themes emerged in two broad categories: 1) developing research capacity; and 2) efficiently defining compelling scientific questions within the local context. Compelling scientific questions included how to deliver inexpensive, scalable, and sustainable interventions using alternative health delivery models that leverage existing human capital, technologies and therapeutics, and entrepreneurial strategies. These broad themes provide perspectives that inform an overarching strategy needed to reduce the heart, lung, blood, and sleep disorders disease burden and global health disparities.

  8. High-dose radiotherapy alone for patients with T4-stage laryngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mucha-Malecka, A. [Maria Sklodowska-Curie Memorial Institute, Krakow (Poland). Dept. of Radiation Oncology; Skladowski, K. [Maria Sklodowska-Curie Memorial Institute, Gliwice (Poland). Dept. of Radiation Oncology


    Background and purpose: The purpose of this retrospective study was to report on the efficacy of radiotherapy alone in patients with T4-stage laryngeal cancer and to establish the prognostic value of (a) the size and location of the extralaryngeal tumor extensions and (b) of emergency tracheostomy. Patients and methods: A group of 114 patients were treated with definitive radiotherapy between 1990 and 1996. The piriform recess was involved in 37 cases (33 %), the base of the tongue and glosso-epiglottic vallecula in 34 cases (30 %), and the hypopharyngeal wall in 10 cases (9 %). In 16 cases (14 %), emergency tracheostomy was performed before radiotherapy. The mean total dose was 68 Gy (range, 60-77.6 Gy). The mean treatment time was 49 days (range, 42-74 days). Results: Actuarial 3-year local control (LC) was noted in 42 % of patients, disease-free survival (DFS) in 35 %, and overall survival (OS) in 40 %. The best prognosis was for the lesion suspected of cartilage infiltration: 56 % 3-year LC. The worst results were noted in the cases with massive infiltrations spreading from the larynx through the hypopharynx: 13 % 3-year LC. Emergency tracheostomy before radiotherapy was significantly connected with the worst treatment results (p = 0.000): 3-year LC in patients with tracheostomy was 0 % vs. 48 % in patients without tracheostomy. Conclusion: Conventional radiotherapy of T4 laryngeal cancer is a method of treatment with limited effectiveness. The efficacy of radiotherapy is dependent on the location and extent of extralaryngeal infiltrations. Emergency tracheostomy is a prognostic factor connected with the worst prognosis. (orig.)

  9. Functional Analysis of the Bacteriophage T4 Rad50 Homolog (gp46) Coiled-coil Domain. (United States)

    Barfoot, Tasida; Herdendorf, Timothy J; Behning, Bryanna R; Stohr, Bradley A; Gao, Yang; Kreuzer, Kenneth N; Nelson, Scott W


    Rad50 and Mre11 form a complex involved in the detection and processing of DNA double strand breaks. Rad50 contains an anti-parallel coiled-coil with two absolutely conserved cysteine residues at its apex. These cysteine residues serve as a dimerization domain and bind a Zn(2+) cation in a tetrathiolate coordination complex known as the zinc-hook. Mutation of the zinc-hook in bacteriophage T4 is lethal, indicating the ability to bind Zn(2+) is critical for the functioning of the MR complex. In vitro, we found that complex formation between Rad50 and a peptide corresponding to the C-terminal domain of Mre11 enhances the ATPase activity of Rad50, supporting the hypothesis that the coiled-coil is a major conduit for communication between Mre11 and Rad50. We constructed mutations to perturb this domain in the bacteriophage T4 Rad50 homolog. Deletion of the Rad50 coiled-coil and zinc-hook eliminates Mre11 binding and ATPase activation but does not affect its basal activity. Mutation of the zinc-hook or disruption of the coiled-coil does not affect Mre11 or DNA binding, but their activation of Rad50 ATPase activity is abolished. Although these mutants excise a single nucleotide at a normal rate, they lack processivity and have reduced repetitive exonuclease rates. Restricting the mobility of the coiled-coil eliminates ATPase activation and repetitive exonuclease activity, but the ability to support single nucleotide excision is retained. These results suggest that the coiled-coiled domain adopts at least two conformations throughout the ATPase/nuclease cycle, with one conformation supporting enhanced ATPase activity and processivity and the other supporting nucleotide excision.

  10. Nueva Área Terminal (NAT del aeropuerto de Madrid-Barajas T-4

    Directory of Open Access Journals (Sweden)

    Lamela, A.


    Full Text Available This paper deals with the New Terminal Area of the Barajas airport. Its first part indicates the participants in the design and construction, as well as some general data. In the second part, organised like a data chart, technical data, such as general information, construction aspects, parking area, data about the building itself and others, are expressed in a concise way. The third part analyzes the construction aspects of the NAT Building, related to the power efficiency. The paper ends with a note that the author of the project has considered of interest about the functionality of the T4. Drawings, details and photographs that show the work in their total magnitude are also included.El articulo que se presenta trata de la Nueva Área Terminal (NAT del aeropuerto de Barajas y está diferenciado en una primera parte, donde se indican los créditos del proyecto y de la construcción, así como algunos datos generales. En el punto 2 y organizado como ficha, aparecen de forma escueta los datos técnicos, tales como: información general, sobre la construcción, sobre los aparcamientos, sobre el edificio terminal y otras. En el punto 3 se analizan los aspectos de la edificación NAT, relacionados con la eficiencia energética y finaliza el artículo con una nota sobre la funcionalidad de la T4, que el autor del proyecto ha considerado de interés. Se incluyen planos detalles y fotografías que muestran la obra en su total magnitud.

  11. Structure-Function Analysis of the DNA Translocating Portal of the Bacteriophage T4 Packaging Machine (United States)

    Padilla-Sanchez, Victor; Gao, Song; Kim, Hyung Rae; Kihara, Daisuke; Sun, Lei; Rossmann, Michael G.; Rao, Venigalla B.


    Tailed bacteriophages and herpesviruses consist of a structurally well conserved dodecameric portal at a special five-fold vertex of the capsid. The portal plays critical roles in head assembly, genome packaging, neck/tail attachment, and genome ejection. Although the structures of portals from phages φ29, SPP1 and P22 have been determined, their mechanistic roles have not been well understood. Structural analysis of phage T4 portal (gp20) has been hampered because of its unusual interaction with the E. coli inner membrane. Here, we predict atomic models for the T4 portal monomer and dodecamer, and fit the dodecamer into the cryoEM density of the phage portal vertex. The core structure, like that from other phages, is cone-shaped with the wider end containing the “wing” and “crown” domains inside the phage head. A long “stem” encloses a central channel, and a narrow “stalk” protrudes outside the capsid. A biochemical approach was developed to analyze portal function by incorporating plasmid-expressed portal protein into phage heads and determining the effect of mutations on head assembly, DNA translocation, and virion production. We found that the protruding loops of the stalk domain are involved in assembling the DNA packaging motor. A loop that connects the stalk to the channel might be required for communication between the motor and portal. The “tunnel” loops that project into the channel are essential for sealing the packaged head. These studies established that the portal is required throughout the DNA packaging process, with different domains participating at different stages of genome packaging. PMID:24126213

  12. Report of the Snowmass T4 working group on particle sources: Positron sources, anti-proton sources and secondary beams

    Energy Technology Data Exchange (ETDEWEB)

    N. Mokhov et al.


    This report documents the activities of the Snowmass 2001 T4 Particle Sources Working Group. T4 was charged with examining the most challenging aspects of positron sources for linear colliders and antiproton sources for proton-antiproton colliders, and the secondary beams of interest to the physics community that will be available from the next generation of high-energy particle accelerators. The leading issues, limiting technologies, and most important R and D efforts of positron production, antiproton production, and secondary beams are discussed in this paper. A listing of T4 Presentations is included.

  13. Changes in arterial stiffness, carotid intima-media thickness, and epicardial fat after L-thyroxine replacement therapy in hypothyroidism. (United States)

    del Busto-Mesa, Abdel; Cabrera-Rego, Julio Oscar; Carrero-Fernández, Lisván; Hernández-Roca, Cristina Victoria; González-Valdés, Jorge Luis; de la Rosa-Pazos, José Eduardo


    To assess the relationship between primary hypothyroidism and subclinical atherosclerosis and its potential changes with L-thyroxine replacement therapy. A prospective cohort study including 101 patients with primary hypothyroidism and 101 euthyroid patients as controls was conducted from July 2011 to December 2013. Clinical, anthropometrical, biochemical, and ultrasonographic parameters were assessed at baseline and after one year of L-thyroxine replacement therapy. At baseline, hypothyroid patients had significantly greater values of blood pressure, total cholesterol, VLDL cholesterol, left ventricular mass, epicardial fat, and carotid intima-media thickness as compared to controls. Total cholesterol, VLDL cholesterol, ventricular diastolic function, epicardial fat, carotid intima-media thickness, carotid local pulse wave velocity, pressure strain elastic modulus, and β arterial stiffness index showed a significant and positive correlation with TSH levels. After one year of replacement therapy, patients with hypothyroidism showed changes in total cholesterol, VLDL cholesterol, TSH, carotid intima-media thickness, and arterial stiffness parameters. Primary hypothyroidism is characterized by an increased cardiovascular risk. In these patients, L-thyroxine replacement therapy for one year is related to decreased dyslipidemia and improvement in markers of subclinical carotid atherosclerosis. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  14. Risk of Depression, Chronic Morbidities, and l-Thyroxine Treatment in Hashimoto Thyroiditis in Taiwan: A Nationwide Cohort Study. (United States)

    Lin, I-Ching; Chen, Hsin-Hung; Yeh, Su-Yin; Lin, Cheng-Li; Kao, Chia-Hung


    The aim of this study was to evaluate the risk of depression in and effect of L-thyroxine therapy on patients with Hashimoto thyroiditis (HT) in Taiwan.In this retrospective, nationwide cohort study, we retrieved data from the Longitudinal Health Insurance Database 2000. We collected data of 1220 patients with HT and 4880 patients without HT for the period 2000 to 2011. The mean follow-up period for the HT cohort was 5.77 years. Univariate and multivariate Cox proportional hazards regression models were used to estimate the risk of depression in the HT cohort.In the HT cohort, 89.6% of the patients were women. Compared with the non-HT cohort, the HT cohort exhibited a higher prevalence of diabetes mellitus, hyperlipidemia, and coronary artery disease. Furthermore, the HT cohort showed a higher overall incidence of depression compared with the non-HT cohort (8.67 and 5.49 per 1000 person-year; crude hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.18-2.13). The risk of depression decreased after administration of L-thyroxine treatment for more than 1 year (adjusted HR = 1.02; 95% CI = 0.66-1.59).In Taiwan, the overall incidence of depression was greater in the young HT cohort. L-thyroxine treatment reduced the risk of depression.

  15. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring. (United States)

    Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Christiansen, Sofie; Hass, Ulla


    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T₄) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gestation and lactation. Total T₄ serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T₄ in dams, but no significant effects on T₄ levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure through maternal milk, a second study using direct per oral pup exposure from postnatal day 3-16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T₄ reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing that in rats lactational transfer of triclosan seems limited. Since an optimal study design for testing potential developmental neurotoxicants in rats, should include exposure during both the pre- and postnatal periods of brain development, we suggest that in the case of triclosan, direct dosing of pups may be the best way to obtain that goal.

  16. Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation

    National Research Council Canada - National Science Library

    Choudhury, Nila Roy; Nowak, Jakub S; Zuo, Juan; Rappsilber, Juri; Spoel, Steven H; Michlewski, Gracjan


    .... Lin28a is a conserved RNA binding protein involved in pluripotency and tumorigenesis that was previously shown to trigger TuT4-mediated pre-let-7 uridylation, inhibiting its processing and targeting it for degradation...

  17. ${\\cal N}=4$ Supersymmetric Yang-Mills Theory on Orbifold-$T^4\\/{\\bf Z}_$2 Higher Rank Case

    CERN Document Server

    Jinzenji, M; Jinzenji, Masao; Sasaki, Toru


    We derive the partition function of ${\\cal N}=4$ supersymmetric Yang-Mills theory on orbifold-$T^4/{\\bf Z}_2$ for SU(N). We generalize our previous work for SU(2) to the SU(N) case. These partition functions can be factorized into product of bulk contribution of quotient space $T^4/{\\bf Z}_2$ and of blow-up formula including $A_{N-1}$ theta functions with level N.

  18. T cell antigen receptor expression by subsets of Ly-2-L3T4- (CD8-CD4-) thymocytes

    DEFF Research Database (Denmark)

    Wilson, A; Ewing, T; Owens, T


    The V beta 8-specific mAb F23.1 and KJ16 were used as fluorescent stains to test for TCR expression on the surface of subpopulations of early, CD4-CD8- (L3T4-Ly-2-) thymocytes from adult CBA mice. A surprisingly high proportion (27%) of Ly-2-L3T4- thymocytes were strongly F23.1 and KJ16 positive....

  19. Vaccination against Very Virulent Infectious Bursal Disease Virus Using Recombinant T4 Bacteriophage Displaying Viral Protein VP2

    Institute of Scientific and Technical Information of China (English)

    Yong-Chang CAO; Quan-Cheng SHI; Jing-Yun MA; Qing-Mei XIE; Ying-Zuo BI


    In order to develop a desirable inexpensive, effective and safe vaccine against the very virulent infectious bursal disease virus (vvIBDV), we tried to take advantage of the emerging T4 bacteriophage surface protein display system. The major immunogen protein VP2 from the vvIBDV strain HK46 was fused to the nonessential T4 phage surface capsid protein, a small outer capsid (SOC) protein, resulting in the 49 kDa SOC-VP2 fusion protein, which was verified by sodium dodecylsulfate polyacrylamide gel electrophoresis and Western blot. Immunoelectromicroscopy showed that the recombinant VP2 protein was successfully displayed on the surface of the T4 phage. The recombinant VP2 protein is antigenic and showed reactivities to various monoclonal antibodies (mAbs) against IBDV, whereas the wild-type phage T4 could not react to any mAb. In addition, the recombinant VP2 protein is immunogenic and elicited specific antibodies in immunized specific pathogen free (SPF) chickens. More significantly, immunization of SPF chickens with the recombinant T4-VP2 phage protected them from infection by the vvIBDV strain HK46. When challenged with the vvIBDV strain HK46 at a dose of 100 of 50% lethal dose (LD50) per chicken 4 weeks after the booster was given, the group vaccinated with the T4-VP2 recombinant phage showed no clinical signs of disease or death, wh ereas the unvaccinated group and the group vaccinated with the wild-type T4phage exhibited 100% clinical signs of disease and bursal damages, and 30%-40% mortality. Collectively,the data herein showed that the T4-displayed VP2 protein might be an inexpensive, effective and safe vaccine candidate against vvIBDV.

  20. Structure of the small outer capsid protein, Soc: a clamp for stabilizing capsids of T4-like phages. (United States)

    Qin, Li; Fokine, Andrei; O'Donnell, Erin; Rao, Venigalla B; Rossmann, Michael G


    Many viruses need to stabilize their capsid structure against DNA pressure and for survival in hostile environments. The 9-kDa outer capsid protein (Soc) of bacteriophage T4, which stabilizes the virus, attaches to the capsid during the final stage of maturation. There are 870 Soc molecules that act as a "glue" between neighboring hexameric capsomers, forming a "cage" that stabilizes the T4 capsid against extremes of pH and temperature. Here we report a 1.9 A resolution crystal structure of Soc from the bacteriophage RB69, a close relative of T4. The RB69 crystal structure and a homology model of T4 Soc were fitted into the cryoelectron microscopy reconstruction of the T4 capsid. This established the region of Soc that interacts with the major capsid protein and suggested a mechanism, verified by extensive mutational and biochemical studies, for stabilization of the capsid in which the Soc trimers act as clamps between neighboring capsomers. The results demonstrate the factors involved in stabilizing not only the capsids of T4-like bacteriophages but also many other virus capsids.

  1. Combined measurement of thyroid and plasma homocysteic acid for detecting the severity of vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Bin Zhao; Junjian Zhang; Shifeng Wang; Guanghui Chen; Fayun Hu


    and content of homocysteic acid was measured with high performance liquid chromatogram (HPLC) electrochemical detection.MAIN OUTCOME MEASURES: Levels of homocysteic acid and thyroxine among patients with vascular dementia and non-dementia cerebral infarction.RESULTS: A total of 38 patients with vascular dementia and 40 patients with non-dementia cerebral infarction were involved in the final analysis. ① Levels of triiodothyronine (T3), thyroxine (T4) and free T3 (FT3) were (0.9±0.4) μg/L, (92.9±26.4) μg/L and (3.9±1.8) pmol/L in vascular dementia group respectively, which were higher than those in control group [(1.3±0.3) μg/L, (110.2±28.7) μg/L, (7.2±2.1) pmol/L, t=2.766 6-7.433 6, P<0.01]; while, level of homocysteic acid was (29.57±7.12) μmol/L in vascular dementia group, which was higher than that in control group [(24.53±4.98) μmol/L, t =3.637 7, P < 0.01]. There were no significant differences of free T4 (FT4) and thyrotropic-stimulating hormone (TSH) between the two groups (P> 0.05). ② Levels of FT3of patients with mild, moderate and severe vascular dementia were (1.0±0.2), (0.9±0.1) and (0.8±0.1) μg/L,respectively; levels of homocysteic acid were (26.52±4.84), (29.59±5.56) and (32.71±6.17) μmol/L,respectively. There were significant differences among patients at the three degrees of vascular dementia (F=3.59-32.4, P < 0.01). However, there were no significant differences of T4, FT4 and TSH among the three kinds of patients (P> 0.05).CONCLUSION: Levels of thyroxine of patients with vascular dementia decrease; however, levels of homocysteic acid increase. Therefore, the results can indirectly reflect severities of vascular dementia.

  2. Oral T4-like phage cocktail application to healthy adult volunteers from Bangladesh

    Energy Technology Data Exchange (ETDEWEB)

    Sarker, Shafiqul Alam, E-mail: [International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212 (Bangladesh); McCallin, Shawna; Barretto, Caroline [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Berger, Bernard, E-mail: [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Pittet, Anne-Cecile [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Sultana, Shamima, E-mail: [International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212 (Bangladesh); Krause, Lutz, E-mail: [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Huq, Sayeda, E-mail: [International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212 (Bangladesh); Bibiloni, Rodrigo, E-mail: [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Bruttin, Anne, E-mail: [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Reuteler, Gloria, E-mail: [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Bruessow, Harald, E-mail: [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland)


    The genomic diversity of 99 T4-like coliphages was investigated by sequencing an equimolar mixture with Illumina technology and screening them against different databases for horizontal gene transfer and undesired genes. A 9-phage cocktail was given to 15 healthy adults from Bangladesh at a dose of 3 Multiplication-Sign 10{sup 9} and 3 Multiplication-Sign 10{sup 7} plaque-forming units and placebo respectively. Phages were detected in 64% of the stool samples when subjects were treated with higher titer phage, compared to 30% and 28% with lower-titer phage and placebo, respectively. No Escherichia coli was present in initial stool samples, and no amplification of phage was observed. One percent of the administered oral phage was recovered from the feces. No adverse events were observed by self-report, clinical examination, or from laboratory tests for liver, kidney, and hematology function. No impact of oral phage was seen on the fecal microbiota composition with respect to bacterial 16S rRNA from stool.

  3. Improvement on the Fatigue Performance of 2024-T4 Alloy by Synergistic Coating Technology

    Directory of Open Access Journals (Sweden)

    Xi-Shu Wang


    Full Text Available In this paper, rotating bending fatigue tests of 2024-T4 Al alloy with different oxide coatings were carried out. Compared to the uncoated and previously reported oxide coatings of aluminum alloys, the fatigue strength is able to be enhanced by using a novel oxide coating with sealing pore technology. These results indicate that the better the coating surface quality is, the more excellent the fatigue performance under rotating bending fatigue loading is. The improvement on the fatigue performance is mainly because the fatigue crack initiation and the early stage of fatigue crack growth at the coating layer can be delayed after PEO coating with pore sealing. Therefore, it is a so-called synergistic coating technology for various uses, including welding thermal cracks and filling micro-pores. The effects of different oxide coatings on surface hardness, compressive residual stress, morphology and fatigue fracture morphology are discussed. A critical compressive residual stress of about 95–100 MPa is proposed.

  4. T4 bacteriophage conjugated magnetic particles for E. coli capturing: Influence of bacteriophage loading, temperature and tryptone. (United States)

    Liana, Ayu Ekajayanthi; Marquis, Christopher P; Gunawan, Cindy; Gooding, J Justin; Amal, Rose


    This work demonstrates the use of bacteriophage conjugated magnetic particles (Fe3O4) for the rapid capturing and isolation of Escherichia coli. The investigation of T4 bacteriophage adsorption to silane functionalised Fe3O4 with amine (NH2), carboxylic (COOH) and methyl (CH3) surface functional groups reveals the domination of net electrostatic and hydrophobic interactions in governing bacteriophage adsorption. The bare Fe3O4 and Fe3O4-NH2 with high T4 loading captured 3-fold more E. coli (∼70% capturing efficiency) compared to the low loading T4 on Fe3O4-COOH, suggesting the significance of T4 loading in E. coli capturing efficiency. Importantly, it is further revealed that E. coli capture is highly dependent on the incubation temperature and the presence of tryptone in the media. Effective E. coli capturing only occurs at 37°C in tryptone-containing media with the absence of either conditions resulted in poor bacteria capture. The incubation temperature dictates the capturing ability of Fe3O4/T4, whereby T4 and E. coli need to establish an irreversible binding that occurred at 37°C. The presence of tryptophan-rich tryptone in the suspending media was also critical, as shown by a 3-fold increase in E. coli capture efficiency of Fe3O4/T4 in tryptone-containing media compared to that in tryptone-free media. This highlights for the first time that successful bacteria capturing requires not only an optimum tailoring of the particle's surface physicochemical properties for favourable bacteriophage loading, but also an in-depth understanding of how factors, such as temperature and solution chemistry influence the subsequent bacteriophage-bacteria interactions. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Post-transcriptional control by bacteriophage T4: mRNA decay and inhibition of translation initiation

    Directory of Open Access Journals (Sweden)

    Miller Eric S


    Full Text Available Abstract Over 50 years of biological research with bacteriophage T4 includes notable discoveries in post-transcriptional control, including the genetic code, mRNA, and tRNA; the very foundations of molecular biology. In this review we compile the past 10 - 15 year literature on RNA-protein interactions with T4 and some of its related phages, with particular focus on advances in mRNA decay and processing, and on translational repression. Binding of T4 proteins RegB, RegA, gp32 and gp43 to their cognate target RNAs has been characterized. For several of these, further study is needed for an atomic-level perspective, where resolved structures of RNA-protein complexes are awaiting investigation. Other features of post-transcriptional control are also summarized. These include: RNA structure at translation initiation regions that either inhibit or promote translation initiation; programmed translational bypassing, where T4 orchestrates ribosome bypass of a 50 nucleotide mRNA sequence; phage exclusion systems that involve T4-mediated activation of a latent endoribonuclease (PrrC and cofactor-assisted activation of EF-Tu proteolysis (Gol-Lit; and potentially important findings on ADP-ribosylation (by Alt and Mod enzymes of ribosome-associated proteins that might broadly impact protein synthesis in the infected cell. Many of these problems can continue to be addressed with T4, whereas the growing database of T4-related phage genome sequences provides new resources and potentially new phage-host systems to extend the work into a broader biological, evolutionary context.

  6. Trophoblast Glycoprotein (TPGB/5T4) in Human Placenta: Expression, Regulation, and Presence in Extracellular Microvesicles and Exosomes. (United States)

    Alam, S M K; Jasti, S; Kshirsagar, S K; Tannetta, D S; Dragovic, R A; Redman, C W; Sargent, I L; Hodes, H C; Nauser, T L; Fortes, T; Filler, A M; Behan, K; Martin, D R; Fields, T A; Petroff, B K; Petroff, M G


    Many parallels exist between growth and development of the placenta and that of cancer. One parallel is shared expression of antigens that may have functional importance and may be recognized by the immune system. Here, we characterize expression and regulation of one such antigen, Trophoblast glycoprotein (TPGB; also called 5T4), in the placenta across gestation, in placentas of preeclamptic (PE) pregnancies, and in purified microvesicles and exosomes. Trophoblast glycoprotein expression was analyzed by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry. Regulation of 5T4 in cytotrophoblast cells was examined under either differentiating conditions of epidermal growth factor or under varying oxygen conditions. Microvesicles and exosomes were purified from supernatant of cultured and perfused placentas. Trophoblast glycoprotein expression was prominent at the microvillus surface of syncytiotrophoblast and on the extravillous trophoblast cells, with minimal expression in undifferentiated cytotrophoblasts and normal tissues. Trophoblast glycoprotein expression was elevated in malignant tumors. In cytotrophoblasts, 5T4 was induced by in vitro differentiation, and its messenger RNA (mRNA) was increased under conditions of low oxygen. PE placentas expressed higher 5T4 mRNA than matched control placentas. Trophoblast glycoprotein was prominent within shed placental microvesicles and exosomes. Given the potential functional and known immunological importance of 5T4 in cancer, these studies reveal a class of proteins that may influence placental development and/or sensitize the maternal immune system. In extravillous trophoblasts, 5T4 may function in epithelial-to-mesenchymal transition during placentation. The role of syncytiotrophoblast 5T4 is unknown, but its abundance in shed syncytial vesicles may signify route of sensitization of the maternal immune system.

  7. Increased thyroxine sulfate levels in critically ill patients as a result of a decreased hepatic type I deiodinase activity

    NARCIS (Netherlands)

    R.P. Peeters (Robin); M.H.A. Kester (Monique); P.J. Wouters (Pieter); E. Kaptein (Ellen); H. van Toor (Hans); T.J. Visser (Theo); G. van den Berghe (Greet)


    textabstractIntroduction: Marked changes in peripheral thyroid hormone metabolism occur in critical illness, resulting in low serum T3 and high rT 3 levels. In this study, we investigated whether T4S levels are increased in patients who died after intensive care and whether T4S levels are correlated

  8. Conversion of thyroxine to 3,3',5'-triiodothyronine in the guinea pig placenta: in vivo studies

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, E.; Gibbens, M.; Thomas, C.R.; Lowy, C.; Burke, C.W.


    Studies of placental inner-ring deiodination of T4 were carried out in pregnant guinea pigs, by in situ placental perfusion. When (/sup 131/I)T4 and (/sup 125/I)rT3 were administered to the mother, the ratio of fetal side to maternal side (/sup 131/I)rT3 was more than 10 times greater than the corresponding ratio for (/sup 125/I)rT3. When radiolabeled T4 was supplied to the fetal side of the placenta in perfusion fluid, and the perfusate recycled through the placental circuit, there was a progressive increase in labeled rT3 concentration in the perfusate. These results indicate that the guinea pig placenta actively deiodinates both maternal and fetal T4 in the inner ring in vivo. We found evidence of very little outer ring deiodination of either T4 or rT3. The quantitative contribution of placental deiodination of maternal T4 to circulating rT3 in the fetus appears to be small; however, placental deiodination of fetal T4 (about 0.5 nmol/kg fetal BW X day) could contribute significantly to fetal rT3 levels. Our observations are consistent with the hypothesis that placental inner-ring deiodination of T4 plays a part in the regulation of fetal iodothyronine metabolism.

  9. Hashimoto's thyroiditis, risk of coronary heart disease, and L-thyroxine treatment: a nationwide cohort study. (United States)

    Chen, Wei-Hung; Chen, Yen-Kung; Lin, Cheng-Li; Yeh, Jiann-Horng; Kao, Chia-Hung


    Our objective was to investigate the risk of coronary heart disease (CHD) in patients with Hashimoto's thyroiditis (HT). The Taiwan National Health Insurance Research Database was used to conduct a retrospective cohort analysis. The cohort study consisted of 1165 newly diagnosed HT patients and 4660 matched controls (non-HT patients) from 2000 to 2010. The median follow-up time was 5.46 years. The risk of developing CHD for HT patients was measured using the Cox proportional hazards model. The risk of developing CHD in HT patients was increased compared with the non-HT controls, with an adjusted hazard ratio (HR) of 1.44 (95% confidence interval [CI] = 1.05-1.99). The risk was significant in women but not in men, and restricted to subjects younger than 49 years. HT remained an independent risk factor after adjusting for comorbidities; however, combining with hypertension or hyperlipidemia further increased the risk of CHD (adjusted HR = 2.06, 95% CI = 1.46-2.92; and adjusted HR = 1.83, 95% CI = 1.31-2.55, respectively). Furthermore, HT without T4 treatment and HT with treatment for less than 1 year were associated with higher risk of CHD (adjusted HR = 1.55, 95% CI = 0.98-2.46; and adjusted HR = 2.42, 95% CI = 1.43-3.97, respectively). The risk of CHD decreased after treatment with T4 for more than 1 year and did not differ from the non-HT cohort (adjusted HR = 0.84, 95% CI = 0.0.47-1.52). Patients with HT, are at higher risk of developing CHD compared with the general population. Treatment with T4 reduces the risk of CHD.

  10. Adjustment of L-T4 substitutive therapy in pregnant women with subclinical, overt or post-ablative hypothyroidism. (United States)

    Verga, Uberta; Bergamaschi, Silvia; Cortelazzi, Donatella; Ronzoni, Stefania; Marconi, Anna Maria; Beck-Peccoz, Paolo


    Maternal hyperthyrotropinaemia is associated with an increased risk of adverse maternal and neonatal outcomes. Physiological changes during pregnancy require an increased production of thyroid hormones (or an increase in daily substitutive doses of L-T4 in hypothyroid patients) to meet the maternal and foetal needs. The aim of the study was to evaluate variations of substitutive L-T4 doses that are able to maintain serum TSH between 0.5 and 2.5 mU/l in pregnant women with subclinical- (SH), overt- (OH) and post-ablative (PH) hypothyroidism. This was a retrospective study on hypothyroid pregnant women referred to the out-patient department between January 2004 and December 2006. A total of 185 pregnant women were studied during gestation; 155 patients (76 SH, 52 OH, 27 PH) were already on L-T4 before conception and 30 (SH) started L-T4 therapy during gestation. Thyroid function and body weight were evaluated every 4-6 weeks. In the group of patients already treated before conception, 134 (86.5%) increased L-T4 doses during gestation one or more times, eight (6%) reached a definitive therapeutic dosage within the 12th week of pregnancy, 64 (47.8%) within the 20th week and 62 (46.2%) within the 31st week. This initial L-T4 increase at the first evaluation during pregnancy was 22.9 +/- 9.8 microg/day. The final L-T4 doses were significantly different depending on the aetiology, being 101.0 +/- 24.6 microg/day in SH, 136.8 +/- 30.4 microg/day in OH and 159.0 +/- 24.6 microg/day in PH. The per cent increase of L-T4, expressed as Delta% of absolute dose, was +70% in SH, +45% in OH and +49% in PH as compared to baseline dose. In SH patients diagnosed during gestation, the starting L-T4 dose was higher than L-T4 dose before pregnancy of SH patients already treated (75.4 +/- 14.5 and 63.2 +/- 20.1 microg/day, respectively), whereas the final doses were similar. L-T4 dose was increased one or more times in 24 patients (80%), 8 reached the definitive dosage within the second

  11. T4 phage lysozyme: a protein designed for understanding tryptophan photophysics (United States)

    Hudson, Bruce S.; Harris, Dan


    Bacteriophage T4 lysozyme in its wild type form contains three tryptophan residues (at sequence postions 126, 138 and 158). These three residues are in rather different environments in the protein: 126 and 158 are near the protein surface while residue 138 is more buried. T4 lysozyme has been genetically engineered to prepare all possible variants in which one or more of the tryptophan residues have been replaced by tyrosine. The available data supports the hypothesis that this substitution has, at most, a very minor effect on the structure of the protein. The three species with single tryptophan residues have been investigated in detail. The surface location of residue 126 compared to the buried location of residue 138 is reflected in the difference in collisional quenching observed with added potassium iodide. It is found that the spectral and radiative properties of the three proteins are very similar but that their radiationless decay properties are quite distinct. This is apparently due to short-range collisional quenching by neighboring side chains. Comparison with solution quenching measurements permits the identification of the specific quenching groups involved for each tryptophan residue and provides a semi-quantitative rationale for the radiationless decay rate. This collisional quenching interpretation is supported by mutational effects on fluorescence quantum yield. This simple picture of the behavior of these single-tryptophan proteins is clearly revealed in this particular case because of the unambiguous choice of collisional quenching groups. The time dependence of the fluorescence decay of each of these single-tryptophan proteins is quite complex. Several methods of analysis are presented and discussed in terms of their underlying physical basis. Internal collisional quenching, as suggested from the comparative studies, is expected to lead to non-exponential behavior. This is consistent with the observed time dependence. Analysis of the temporal

  12. Preoperative radiation with concurrent 5-fluorouracil for locally advanced T4-primary rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, C.; Grabenbauer, G.G.; Sauer, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Radiation Oncology; Schick, C.; Hohenberger, W. [Erlangen-Nuernberg Univ., Erlangen (Germany). Chirurgische Klinik mit Poliklinik; Papadopoulos, T. [Erlangen-Nuernberg Univ., Erlangen (Germany). Abt. fuer Klinische Pathologie


    Herein we report on the curative resectability rate, acute toxicities, surgical complications, local control and 5-year survival rates achieved with a more aggressive multimodality regimen, including preoperative radiochemotherapy. Patients and Methods: Between 1/1990 and 12/1998, a total of 31 patients with cT4-rectal cancer were treated at our institution. All patients presented with tumor contiguous or adherent to adjacent pelvic organs. Eight patients had synchronous distant metastases. A total radiation dose of 50.4 Gy with a small-volume boost of 5.4 to 9 Gy was delivered (single dose: 1.8 Gy). 5-FU was scheduled as a continuous infusion of 1000 mg/m{sup 2} per 24 hours on days 1 to 5 and 29 to 33. Six weeks after completion of radiochemotherapy, patients were reassessed for resectability. Results: After preoperative radiochemotherapy, 29/31 patients (94%) underwent surgery with curative intent. Resection of the pelvic tumor with negative margins was achieved in 26/31 patients (84%), 3 patients had microscopic residual pelvic disease. In 3/8 patients with distant spread at presentation a complete resection of metastases was finally accomplished. Toxicity of radiochemotherapy occurred mainly as diarrhea (NCI-CTC Grade 3: 23%), dermatitis (Grade 3: 16%) and leucopenia (Grade 3: 10%). Surgical complications appeared as anastomotic leakage in 3, wound infection in 2, fistula, abscess and hemorrhage in 1 patient, respectively. With a median follow-up of 33 months, local failure after curative resection was observed in 4 patients (19%), 3 patients (14%) developed distant metastases. The 5-year overall survival rate for the entire group of 31 patients was 51%, following curative surgery 68%. (orig.) [German] Wir analysierten die Rate an kurativen (R0) Resektionen nach praeoperativer Radiochemotherapie, die Toxizitaet der Radiochemotherapie, die chirurgische Morbiditaet sowie die lokale Kontrolle und das Fuenf-Jahres-Gesamtueberleben nach multimodaler Therapie

  13. Molecular interactions and residues involved in force generation in the T4 viral DNA packaging motor. (United States)

    Migliori, Amy D; Smith, Douglas E; Arya, Gaurav


    Many viruses utilize molecular motors to package their genomes into preformed capsids. A striking feature of these motors is their ability to generate large forces to drive DNA translocation against entropic, electrostatic, and bending forces resisting DNA confinement. A model based on recently resolved structures of the bacteriophage T4 motor protein gp17 suggests that this motor generates large forces by undergoing a conformational change from an extended to a compact state. This transition is proposed to be driven by electrostatic interactions between complementarily charged residues across the interface between the N- and C-terminal domains of gp17. Here we use atomistic molecular dynamics simulations to investigate in detail the molecular interactions and residues involved in such a compaction transition of gp17. We find that although electrostatic interactions between charged residues contribute significantly to the overall free energy change of compaction, interactions mediated by the uncharged residues are equally if not more important. We identify five charged residues and six uncharged residues at the interface that play a dominant role in the compaction transition and also reveal salt bridging, van der Waals, and solvent hydrogen-bonding interactions mediated by these residues in stabilizing the compact form of gp17. The formation of a salt bridge between Glu309 and Arg494 is found to be particularly crucial, consistent with experiments showing complete abrogation in packaging upon Glu309Lys mutation. The computed contributions of several other residues are also found to correlate well with single-molecule measurements of impairments in DNA translocation activity caused by site-directed mutations.

  14. Stabilization of T4 bacteriophage at acidic and basic pH by adsorption on paper. (United States)

    Meyer, Abigail; Greene, Melissa; Kimmelshue, Chad; Cademartiri, Rebecca


    Bacteriophages find applications in agriculture, medicine, and food safety. Many of these applications can expose bacteriophages to stresses that inactivate them including acidic and basic pH. Bacteriophages can be stabilized against these stresses by materials including paper, a common material in packaging and consumer products. Combining paper and bacteriophages creates antibacterial materials, which can reduce the use of antibiotics. Here we show that adsorption on paper protects T4, T5, and T7 bacteriophage from acidic and basic pH. We added bacteriophages to filter paper functionalized with carboxylic acid (carboxyl methyl cellulose) or amine (chitosan) groups, and exposed them to pH from 5.6 to 14. We determined the number of infective bacteriophages after exposure directly on the paper. All papers extended the lifetime of infective bacteriophage by at least a factor of four with some papers stabilizing bacteriophages for up to one week. The degree of stabilization depended on five main factors (i) the family of the bacteriophage, (ii) the charge of the paper and bacteriophages, (iii) the location of the bacteriophages within the paper, (iv) the ability of the paper to prevent bacteriophage-bacteriophage aggregation, and (v) the sensitivity of the bacteriophage proteins to the tested pH. Even when adsorbed on paper the bacteriophages were able to remove E. coli in milk. Choosing the right paper modification or material will protect bacteriophages adsorbed on that material against detrimental pH and other environmental challenges increasing the range of applications of bacteriophages on materials. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Coordinate Variation in Lengths of Deoxyribonucleic Acid Molecules and Head Lengths in Morphological Variants of Bacteriophage T4 (United States)

    Mosig, Gisela; Carnighan, Janet Renshaw; Bibring, Jane Baxandall; Cole, Robert; Bock, Hans-Georg Otto; Bock, Susan


    We have investigated three classes of small bacteriophage T4 particles which differ from normal T4 particles in length of their deoxyribonucleic acid (DNA), in head length, in protein content, and in density. The different particles contain DNA molecules measuring 0.90, 0.77, or 0.67, respectively, of the normal T4 length. An additional class of viable particles contains DNA molecules of 1.1 unit length. These discrete differences in DNA length correspond to discrete differences in length (but not width) of the respective heads and are roughly proportional to the resulting differences in head volumes. The measured relative dimensions of the different heads fit best the relative dimensions predicted by a quasi-icosahedral model in which the smallest T4 head corresponds to an icosahedron with a triangulation number T = 21. The mid-portion of this structure is thought to be elongated by adding successive rows of gene 23 protein hexamers, the normal T4 head having three added rows. Different mutants produce small particles of the three classes in varying proportions, but no mutant produces exclusively particles of a single class. Particles of each class, with indistinguishable DNA content, show additional minor differences in protein content, as measured by differences in buoyant density and in the relative ratio of 32P to 35S. Images PMID:5025493

  16. Free thyroxine levels are associated with cognitive changes in individuals with a first episode of psychosis: A prospective 1-year follow-up study. (United States)

    Labad, J; Barbero, J D; Gutiérrez-Zotes, A; Montalvo, I; Creus, M; Cabezas, Á; Solé, M; Algora, M J; Garcia-Parés, G; Vilella, E


    The results of previous cross-sectional studies suggest that free thyroxine (FT4) levels are associated with cognitive abilities (particularly attention/vigilance) during the early stages of psychosis. We aimed to explore whether hypothalamic-pituitary-thyroid hormones predict cognitive changes in a 1-year longitudinal study following first episodes of psychosis (FEP). We studied 36 FEP patients and a control group of 50 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH) and FT4 were measured. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery (MCCB). FEP patients were assessed twice (baseline and after 1year), whereas HS were assessed only once. We compared cognitive changes at 1year between three groups based on baseline FT4 levels: 1) lowest quartile (Q1, FT41.54ng/dL). No differences in TSH or FT4 levels were found between HS and FEP patients. All participants had FT4 levels within the normal range. HS outperformed FEP patients in all cognitive tasks. In relation to the relationship between FT4 levels and cognitive changes, a U-shaped pattern was observed: FEP patients from the middle quartiles (Q2-Q3) improved in attention/vigilance, whereas both extreme quartiles (Q1 and Q4) showed a worsening in this cognitive domain over time. Patients with lower FT4 (Q1) showed poorer baseline attention; therefore, lower baseline FT4 levels predicted a poorer prognosis in terms of attention performance. Our study suggests that baseline FT4 levels are associated with changes in attention and vigilance performance over one year in FEP patients.

  17. Recalculation of data from 1990 to 2010 on the effects of highly diluted thyroxine on the metamorphosis of highland amphibians

    Directory of Open Access Journals (Sweden)

    Peter Christian Endler


    Full Text Available Experiments on amphibian metamorphosis can vary considerably in duration. The authors had set themselves the task of defining a generally applicable pooling method for metamorphosis experiments [1]. Normalization with respect to time was done on the assumption that differences in speed of metamorphosis attributable to treatment would override differences in duration between experiments. The problem of artificial differences in variability when comparing and pooling data from several experiments was approached by normalization with respect to time based on the development of both the test and the control animals. The range from 0% to 100% over which the fraction of four-legged animals progresses in the course of an experiment is divided into 10%-intervals and mapped onto a corresponding relative scale. Each measurement is then assigned to the point on the 10%-scale to which it is closest. In this way each reference point is assigned a value giving the number or percentage of four-legged animals at that point. These values are aggregated over all experiments within the test- and control-group. The results of experiments performed over the course of two decades (1990 - 2010 on highland Rana temporaria treated with a homeopathically prepared high dilution of thyroxine (“30x” are presented in full detail based on this normalization method[1]. It was found that differences between treatment groups thus calculated were in line with those obtained with other pooling methods [2]. Thyroxine 30x does slow down metamorphosis in inert highland amphibians. This was observed by 5 researchers in 20 sub-experiments, and it seems to be the most reliable bio-assay found in amphibian research on homeopathy so far2. When experiments were performed with highland animals pretreated by hyperstimulation with molecular thyroxine, slowing down of metamorphosis was again observed (by 3 of 4 researchers in most of 10 sub-experiments.

  18. Necrotizing Meningoencephalitis in a Captive Black and White Ruffed Lemur (Varecia variegata variegata) Caused by Acanthamoeba T4 Genotype. (United States)

    Gaide, N; Pelandakis, M; Robveille, C; Albaric, O; Jouvion, G; Souchon, M; Risler, A; Abadie, J


    A mature male, black and white ruffed lemur (Varecia variegata variegata) died in a zoological garden after a 4-day history of lethargy and non-responsive convulsions. Necropsy and histopathological examinations revealed acute necrotizing and haemorrhagic meningoencephalitis with intralesional amoebas confirmed by immunohistochemistry. Acanthamoeba T4 genotype was identified as the causative agent of the brain lesion, based on amplification and sequencing of 18S ribosomal RNA genes. The presence of free-living amoebas in water and mud from the lemur's environment was investigated by morphological and molecular analyses. The two predominant genera, representing 80% of isolated amoebas, were Naegleria spp. and Acanthamoeba spp. All Acanthamoeba isolates belonged to the T4 genotype. To the author's knowledge, this is the first report of a meningoencephalitis due to Acanthamoeba T4 genotype in Lemuridae with concurrent analysis of pathological tissues and environment.

  19. Increased thyroidal T4 to T3 conversion in autonomously functioning thyroid adenoma: from euthyroidism to thyrotoxicosis.

    LENUS (Irish Health Repository)

    Solter, M


    AIM: The aim was to investigate whether the intrathyroid conversion of T4 to T3 in autonomously functioning thyroid adenoma (AFTA) tissue could influence serum T3 levels and suppression of TSH, especially in patients with borderline thyroid function. PATIENTS AND METHODS: In ten patients with AFTA, thyroidal conversion of T4 to T3 was investigated in nodular and paranodular, TSH-suppressed tissue. All patients had normal serum T4 and suppressed TSH. Serum T3 was normal in six, and borderline or slightly increased in four. AFTA and paranodular tissues were surgically removed and frozen at -70 degrees C, then homogenized in a glass homogenizer, centrifuged at 100,000xg, and particulate fraction collected as a pellet. Analysis mixture consisted of thyroid enzyme suspension in 50 mumol\\/L TRIS buffer with 5 mumol DTT and 200 muL 1.3 mumol T4. Incubation was performed at 37 degrees C and the generation of T3 measured after 5, 10, 20 and 40 minutes respectively. RESULTS: T3 production (pmol\\/mg protein) was significantly higher in AFTA than in paranodular tissues (8.8 1.2\\/Mean +\\/- SE\\/vs. 1.8 +\\/- 0.2; p<0.01), and excessively high (9.8, 14.1, 14.2 and 15.0) in four patients with borderline or slightly supranormal serum T3. A significant correlation was found between serum T3 concentrations and T3 generation (T4 conversion) in AFTA tissues. CONCLUSION: Results suggest that increased thyroidal T4 to T3 conversion in AFTA tissue could be involved in an increased delivery of T3, increased serum T3 and suppressed serum TSH, particularly in patients with the disease evolving from euthyroid to an early hyperthyroid phase.

  20. Actions of a proline analogue, L-thiazolidine-4-carboxylic acid (T4C, on Trypanosoma cruzi.

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    Anahí Magdaleno

    Full Text Available It is well established that L-proline has several roles in the biology of trypanosomatids. In Trypanosoma cruzi, the etiological agent of Chagas' disease, this amino acid is involved in energy metabolism, differentiation processes and resistance to osmotic stress. In this study, we analyzed the effects of interfering with L-proline metabolism on the viability and on other aspects of the T. cruzi life cycle using the proline analogue L- thiazolidine-4-carboxylic acid (T4C. The growth of epimastigotes was evaluated using different concentrations of T4C in standard culture conditions and at high temperature or acidic pH. We also evaluated possible interactions of this analogue with stress conditions such as those produced by nutrient starvation and oxidative stress. T4C showed a dose-response effect on epimastigote growth (IC(50 = 0.89+/-0.02 mM at 28 degrees C, and the inhibitory effect of this analogue was synergistic (p<0.05 with temperature (0.54+/-0.01 mM at 37 degrees C. T4C significantly diminished parasite survival (p<0.05 in combination with nutrient starvation and oxidative stress conditions. Pre-incubation of the parasites with L-proline resulted in a protective effect against oxidative stress, but this was not seen in the presence of the drug. Finally, the trypomastigote bursting from infected mammalian cells was evaluated and found to be inhibited by up to 56% when cells were treated with non-toxic concentrations of T4C (between 1 and 10 mM. All these data together suggest that T4C could be an interesting therapeutic drug if combined with others that affect, for example, oxidative stress. The data also support the participation of proline metabolism in the resistance to oxidative stress.

  1. Divergence of the mRNA targets for the Ssb proteins of bacteriophages T4 and RB69

    Directory of Open Access Journals (Sweden)

    Petrov Vasiliy M


    Full Text Available Abstract The single-strand binding (Ssb protein of phage T4 (T4 gp32, product of gene 32 is a mRNA-specific autogenous translational repressor, in addition to being a sequence-independent ssDNA-binding protein that participates in phage DNA replication, repair and recombination. It is not clear how this physiologically essential protein distinguishes between specific RNA and nonspecific nucleic acid targets. Here, we present phylogenetic evidence suggesting that ssDNA and specific RNA bind the same gp32 domain and that plasticity of this domain underlies its ability to configure certain RNA structures for specific binding. We have cloned and characterized gene 32 of phage RB69, a relative of T4 We observed that RB69 gp32 and T4 gp32 have nearly identical ssDNA binding domains, but diverge in their C-terminal domains. In T4 gp32, it is known that the C-terminal domain interacts with the ssDNA-binding domain and with other phage-induced proteins. In translation assays, we show that RB69 gp32 is, like T4 gp32, an autogenous translational repressor. We also show that the natural mRNA targets (translational operators for the 2 proteins are diverged in sequence from each other and yet can be repressed by either gp32. Results of chemical and RNase sensitivity assays indicate that the gp32 mRNA targets from the 2 related phages have similar structures, but differ in their patterns of contact with the 2 repressors. These and other observations suggest that a range of gp32-RNA binding specificities may evolve in nature due to plasticity of the protein-nucleic acid interaction and its response to modulation by the C-terminal domain of this translational repressor.

  2. Intervalos de referencia para concentraciones séricas de T3 y T4. Estudio preliminar

    Directory of Open Access Journals (Sweden)

    Cecilia Miranda Pantoja


    Full Text Available Fundamento: la determinación cuantitativa de las hormonas tiroideas T3 y T4 reviste gran importancia en el diagnóstico y la evaluación del hipertiroidismo, en especial del hipertiroidismo aislado causado por T3.Objetivo: establecer los intervalos de referencia de T3 y T4 en el laboratorio de medicina nuclear del Hospital General Universitario Dr. Gustavo Aldereguía Lima de Cienfuegos. Métodos: estudio descriptivo y prospectivo realizado mediante el método de radioinmunoanálisis, competencia que se establece entre la T3 y T4 sin marcar, y la marcada por un número limitado de los sitios de unión del anticuerpo específico. Al hacer reaccionar una cantidad fija de trazador y anticuerpo con diferentes cantidades del ligando sin marcar, la cantidad de trazador unido por el anticuerpo será inversamente proporcional a la concentración del ligando sin marcar. Resultados: los valores obtenidos se describen según una distribución gaussiana (media aritmética = 117, desviación estándar =31 para T4; media aritmética = 2,64, desviación estándar = 0,64 para T3, comprobado mediante un test de Chi cuadrado. Los rangos de valores normales obtenidos fueron de de 55 – 178 nmol/L y 1,4 – 3,9 nmol/L para T4 y T3 respectivamente. Conclusiones: los intervalos de referencia obtenidos resultaron más amplios que los propuestos por el productor, sobre todo en el caso de T4.

  3. Prevalence and pattern of nodal metastasis in pT4 gingivobuccal cancers and its implications for treatment

    Directory of Open Access Journals (Sweden)

    H Narendra


    Full Text Available Context: The pattern of nodal spread in oral cancers is largely predictable and treatment of neck can be tailored with this knowledge. Most studies available on the pattern are from the western world and for early cancers of the tongue and floor of the mouth. Aims: The present study was aimed to evaluate the prevalence and pattern of nodal metastasis in patients with pathologic T4 (pT4 buccal/alveolar cancers. Settings and Design: Medical records of the patients with pT4 primary buccal and alveolar squamous cell carcinomas treated by single-stage resection of primary tumor and neck dissection at Gujarat Cancer and Research Institute (GCRI, Ahmedabad, a regional cancer center in India, during September 2004 to August 2006, were analyzed for nodal involvement. Materials and Methods: The study included 127 patients with pT4 buccal/alveolar cancer. Data pertaining to clinical nodal status, histologic grade, pT and pN status (TNM classification of malignant tumors, UICC, 6th edition, 2002, total number of nodes removed, and those involved by tumor, and levels of nodal involvement were recorded. Statistical analysis was performed using the Chi-square test. Results: Fifty percent of the patients did not have nodal metastasis on final histopathology. Occult metastasis rate was 23%. All of these occurred in levels I to III. Among those with clinically palpable nodes, level V involvement was seen only in 4% of the patients with pT4 buccal cancer and 3% of the patients with alveolar cancer. Conclusions: Elective treatment of the neck in the form of selective neck dissection of levels I to III is needed for T4 cancers of gingivobuccal complex due to a high rate of occult metastasis. Selected patients with clinically involved nodes could be well served by a selective neck dissection incorporating levels I to III or IV.

  4. Thyroid Function Test in Thyroid Diseases and Pregnancy - The diagnostic value of free thyroxine by RIA -

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, M. H.; Yoon, H. J.; Shin, Y. T.; Lee, J. C.; Chung, S. I.; Cho, B. Y.; Lee, M. H. [Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, M. C. [Capotal Armed Forces General Hospital, Seoul (Korea, Republic of)


    To evaluate the diagnostic accuracy of the measurement of free thyroxine(FT4) by radioimmunoassay, we measured free T{sub 4} and T{sub 4}, T{sub 3}, T{sub 3}RU, TSH and TBG serum levels by radioimmunoassay in 18 healthy persons and 52 patients with various thyroid diseases and 11 normal pregnant women. The results are as follows. 1) In 19 cases of overt hyperthyroidism, T{sub 3}, free T{sub 4} and FTI, T{sub 4}/TBG ratio reflect hyperfunction in all cases. T{sub 4} is increased in 94%(18/19) and TBG and TSH are decreased in 79%(15/19). 2) In 8 patients with overt hypothyroidism, TSH is increased in all cases and free T{sub 4} and FTI is decreased in all cases. T{sub 4} is decreased in 87.5%(7/8), T{sub 3} is decreased in 75%(6/8) and T{sub 4}/TBG ratio is decreased in 62.5%(5/8). 3) In 5 patients who are clinically in euthyroid state after treatment of hyperthyroidism, T{sub ,}4 free T{sub 4}, FTI and TSH are in the normal range in all cases and T{sub 3} is normal in 60%(3/5) and slightly increased in 40%(2/5). 4) In 10 patients who showed clinically borderline hypothyroidism after treatment of hyperthyroidism, TSH is increased in all cases and free T{sub 4} and FTI are decreased in all cases, but T{sub 4} and T{sub 3}, T{sub 4}/TBG ratio are in the normal limit in all cases. So after treatment of hyperthyroidism, TSH, free T{sub 4} or FTI are recommended as optimal function test. 5) In normal pregnancy, free T{sub 4}, FTI and T{sub 4}/TBG ratio reflect normal function, but the other parameters unreliable due to the influence of increased TBG. Also TBG and TSH level in pregnancy is increased significantly compared with normal healthy control group. 6) The coefficients of correlation between T{sub 4} and FTI were 0.862(p<0.001) and 0.685(p<0.001) between free T{sub 4} and T{sub 4}/TBG ratio. In most patients, diagnostic value of free T{sub 4} was comparable and even superior to FTI, so free T{sub 4} measurement can be used routinely with thyrotropin assay in the

  5. An Inverse Relationship Between Weight and Free Thyroxine During Early Gestation Among Women Treated for Hypothyroidism. (United States)

    Haddow, James E; Neveux, Louis M; Palomaki, Glenn E; Lambert-Messerlian, Geralyn; Malone, Fergal D; D'Alton, Mary E


    Following treatment sufficient to normalize thyrotropin (TSH), nonpregnant hypothyroid adults display higher free thyroxine (FT(4)) concentrations than a reference population. Our aim is to determine whether FT(4) concentrations are higher during pregnancy among women treated for hypothyroidism and whether their weight is associated with FT(4) levels. Weight/FT(4) relationships have not previously been reported in treated hypothyroid adults (either pregnant or nonpregnant). Thyroid-related measurements were available from over 10,000 women at two early pregnancy time periods from the FaSTER (First and Second Trimester Evaluation of Risk for Fetal aneuploidy) trial (1999-2002). All women were receiving routine prenatal care. Present analyses were restricted to 9267 reference women and 306 treated, hypothyroid women with TSH between the 2nd and 98th reference percentiles. We compared FT(4) values between those groups at 11-14 and 15-18 weeks' gestation, using linear regression to estimate FT(4)/maternal weight relationships, after accounting for treatment and other potential covariates. In comparison to reference women, median FT(4) values and percent of FT(4) values ≥95th reference percentile were significantly higher in treated women at both 11-14 and 15-18 weeks' gestation (pwomen, median FT(4) decreased monotonically with increasing weight, regardless of anti-thyroperoxidase antibody status. Maternal age, maternal weight, and treatment status were important predictors of FT(4) levels (pwomen, independent of other factors. Maternal age and weight reduced FT(4) levels by 0.0694 pmol/L/y and 0.0208 pmol/L/kg, respectively. FT(4) concentrations are higher among treated hypothyroid pregnant women than among reference women, and higher maternal weight is associated with lower FT(4) levels, regardless of treatment status. This inverse relationship is not associated with higher TSH levels. While no immediate clinical implications are attached to the current

  6. Experiment K-7-22: Growth Hormone Regulation Synthesis and Secretion in Microgravity. Part 3; Plasma Analysis Hormone Measurements (United States)

    Grindeland, R. E.; Popova, I. A.; Grossman, E.; Rudolph, I.


    Plasma from space flight and tail suspended rats was analyzed for a number of constituents in order to evaluate their metabolic status and endocrine function. The data presented here cover plasma hormone measurements. Corticosterone, thyroxine, and testosterone were measured by radioimmunoassay. Prolactin and growth hormone were measured by double antibody immunoassays using hormones and antisera prepared in house. Data were evaluated by analysis of variance.

  7. The expression of GluT4 mRNA in diabetic rat cardiac muscles%糖尿病大鼠心肌GluT4 mRNA的表达水平

    Institute of Scientific and Technical Information of China (English)

    孙捷; 孔俭; 郑永晨


    目的探讨GluT4 mRNA的表达水平与糖尿病心肌病的相关性.方法采用逆转录聚合酶链式反应的方法对链脲佐菌素(STZ)诱导的糖尿病大鼠心肌GluT4 mRNA的表达水平进行检测并与正常对照组大鼠对比.结果糖尿病大鼠心肌GluT4 mRNA的表达水平明显低于正常对照组(P<0.01).结论在发生糖尿病的同时,大鼠心肌细胞GluT4 mRNA的表达受抑制,含量降低,导致心肌的能量代谢紊乱,引起糖尿病心肌病.

  8. Study on the Interaction of T(4-Mop)PS4 with BSA%T(4-Mop) PS4卟啉与牛血清蛋白相互作用的研究

    Institute of Scientific and Technical Information of China (English)

    张红芬; 郭玉晶; 董川


    Using meso-terakis(4-methoxyl-3-sulfonatophenyl) porphyrin(T(4-Mop)PS4 ) as an electrochemical probe, a new electroanalytical method for the determination of bovine serum albumin (BSA) was established based on the interaction of BSA with T(4-Mop)PS4. A good linear relationship was obtained between the variation of peak current and concentration of BSA in the range of 2. 0 x 10-6 -1.0 ×l0-5 mol · L-1. The limit of detection ( LOD) was 1. 2 ×10-6 mol · L-1 and the relative standard deviation( RSD, n = 8 ) for 5. 0 × 10-6 mol · L-1 BSA was 2. 0% . The supramolecular complex of T(4-Mop)PS4 with BSA was studied by three different methods, including spectrophotom-etry, fluorometry and linear sweep voltammetric (LSV) methods. The binding ratio and binding constant of T(4-Mop)PS4 with BSA were obtained. The experimental data demonstrated that T(4-Mop) PS4 could form a 1 : 1 stable supramolecular complex with BSA, and hydrophobic interaction is the main reaction between them.%以四-(4-甲氧基-3-磺酸基苯)卟啉(T(4-Mop)PS4)为探针,通过T(4-Mop) PS4与牛血清白蛋白(BSA)的相互作用,建立了测定BSA的电化学分析方法.T(4-Mop)PS4的峰电流变化(AIp)与BSA在2.0×10-6~ 1.0×10-5mol·L-1范围内呈良好的线性关系,检出限为1.2×10-6mol· L-1;对5.0×10-6mol·L-1BSA平行测定8次,其相对标准偏差为2.0%,回收率为95%~104%.组氨酸、缬氨酸、苯丙氨酸、丝氨酸、异白氨酸、谷氨酰胺、苏氨酸等氨基酸对BSA的测定不产生干扰.采用紫外可见光度法、荧光光谱法和线性扫描伏安法( LSV)研究了T(4-Mop) PS4与BSA之间的相互作用,并测定了二者相互作用的结合常数和结合比.研究表明,T(4-Mop)PS4与BSA之间主要以疏水作用力结合,形成了1:1的稳定复合物.

  9. Comparative Effectiveness of Replacement Therapy with L-thyroxine in Women with Postoperative and Autoimmune Hypothyroidism

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    M Sch Madiyarova


    Full Text Available Objective. To compare the lipid profile, psychoemotional features, cognitive function, quality of life in women receiving adequate replacement therapy with levothyroxine for postoperative hypothyroidism and autoimmune (Hashimoto's hypothyroidism.Methods. 121 women (18-45 y.o. with primary hypothyroidism receiving levothyroxine for more than one year participated in the study. 66 women with autoimmune hypothyroidism, 55 - with hypothyroidism after subtotal thyroidectomy for Graves' disease. The scores for the Short-Form 36, Hospital Anxiety and Depression Scale, symptoms of hypothyroidism, Inventory of memory and attention, TSH, free T3, free T4 and lipid profiles were analyzed. Results. There were no significant differences between groups in the age, BMI, TSH, fT3, fT4 levels. The total cholesterol was higher in patients with postoperative hypothyroidism in comparison to autoimmune hypothyroidism ( р = 0,041. The levels of social functioning and mental health that reflect mental component of health were lower in patients with autoimmune hypothyroidism than with postoperative hypothyroidism ( p = 0,038, p = 0,019, respectively. The anxiety was higher in the same group ( p = 0,004. There was no difference in memory and attention levels. The anxiety level was higher in autoimmune hypothyroidism and “low-normal” TSH (0,4 - 2 µU/L than in postoperative hypothyroidism and the same TSH ( p = 0,016. Also in the group with postoperative hypothyroidism and “low-normal” TSH the cholesterol and prevalence of hypercholesterolemia were higher than in autoimmune hypothyroidism ( p = 0,017; р = 0,013. Conclusion. In young women with compensated autoimmune hypothyroidism the mental component of health is lower and the anxiety - higher than in postoperative hypothyroidism. Even in stable compensation of postoperative hypothyroidism the cholesterol level is higher comparing to the patients with autoimmune thyroiditis. And even in “low-normal” TSH

  10. Free Thyroxine, Anti-Thyroid Stimulating Hormone Receptor Antibody Titers, and Absence of Goiter Were Associated with Responsiveness to Methimazole in Patients with New Onset Graves' Disease. (United States)

    Choi, Hoon Sung; Yoo, Won Sang


    Anti-thyroid drug therapy is considered a treatment of choice for Graves' disease; however, treatment response varies among individuals. Although several studies have reported risk factors for relapse after initial treatment, few have assessed responsiveness during the early treatment period. Our study aimed to identify the clinical characteristics for responsiveness to methimazole. We included 99 patients diagnosed with Graves' disease for the first time. Drug responsiveness was defined as the correlation coefficients between decreasing rates of free thyroxine level per month and methimazole exposure dose. According to their responsiveness to treatment, the patients were classified into rapid or slow responder groups, and age, sex, free thyroxine level, and thyrotropin binding inhibiting immunoglobulin (TBII) titers were compared between groups. The mean patient age was 44.0±13.5 years and 40 patients were male (40%). The mean TBII titer was 36.6±74.4 IU/L, and the mean free thyroxine concentration was 48.9±21.9 pmol/L. The rapid responder group showed higher TBII titer and free thyroxine level at diagnosis, while age, sex, smoking, and presence of goiter did not differ between the two groups. Logistic regression analyses revealed that high level of serum thyroxine, high titer of TBII, and absence of goiter were significantly associated with a rapid response, while age, sex, and smoking were not significant factors for the prediction of responsiveness. In patients with new onset Graves' disease, high level of free thyroxine, high titer of TBII, and absence of goiter were associated with rapid responsiveness to methimazole treatment.

  11. Preoperative FDG-PET/CT Is an Important Tool in the Management of Patients with Thick (T4) Melanoma. (United States)

    Arrangoiz, Rodrigo; Papavasiliou, Pavlos; Stransky, Carrie A; Yu, Jian Q; Tianyu, Li; Sigurdson, Elin R; Berger, Adam C; Farma, Jeffrey M


    The yield of preoperative PET/CT (PET/CT) for regional and distant metastases for thin/intermediate thickness melanoma is low. Objective of this study is to determine if PET/CT performed for T4 melanomas helps guide management and alter treatment plans. Methods. Retrospective cohort of 216 patients with T4 melanomas treated at two tertiary institutions. Fifty-six patients met our inclusion criteria (T4 lesion, PET/CT and no clinical evidence of metastatic disease). Results. Fifty-six patients (M: 32, F: 24) with median tumor thickness of 6 mm were identified. PET/CT recognized twelve with regional and four patients with metastatic disease. Melanoma-related treatment plan was altered in 11% of the cases based on PET/CT findings. PET/CT was negative 60% of the time, in 35% of the cases; it identified incidental findings that required further evaluation. Conclusion. Patients with T4 lesions, PET/CT changed the treatment plan 18% of the time. Regional findings changed the surgical treatment plan in 11% and the adjuvant plan in 7% of our cases due to the finding of metastatic disease. Additionally 20 patients had incidental findings that required further workup. In this subset of patients, we feel there is a benefit to PET/CT, and further studies should be performed to validate our findings.

  12. Preoperative FDG-PET/CT Is an Important Tool in the Management of Patients with Thick (T4 Melanoma

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    Rodrigo Arrangoiz


    Full Text Available The yield of preoperative PET/CT (PET/CT for regional and distant metastases for thin/intermediate thickness melanoma is low. Objective of this study is to determine if PET/CT performed for T4 melanomas helps guide management and alter treatment plans. Methods. Retrospective cohort of 216 patients with T4 melanomas treated at two tertiary institutions. Fifty-six patients met our inclusion criteria (T4 lesion, PET/CT and no clinical evidence of metastatic disease. Results. Fifty-six patients (M: 32, F: 24 with median tumor thickness of 6 mm were identified. PET/CT recognized twelve with regional and four patients with metastatic disease. Melanoma-related treatment plan was altered in 11% of the cases based on PET/CT findings. PET/CT was negative 60% of the time, in 35% of the cases; it identified incidental findings that required further evaluation. Conclusion. Patients with T4 lesions, PET/CT changed the treatment plan 18% of the time. Regional findings changed the surgical treatment plan in 11% and the adjuvant plan in 7% of our cases due to the finding of metastatic disease. Additionally 20 patients had incidental findings that required further workup. In this subset of patients, we feel there is a benefit to PET/CT, and further studies should be performed to validate our findings.

  13. Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation. (United States)

    Choudhury, Nila Roy; Nowak, Jakub S; Zuo, Juan; Rappsilber, Juri; Spoel, Steven H; Michlewski, Gracjan


    RNA binding proteins have thousands of cellular RNA targets and often exhibit opposite or passive molecular functions. Lin28a is a conserved RNA binding protein involved in pluripotency and tumorigenesis that was previously shown to trigger TuT4-mediated pre-let-7 uridylation, inhibiting its processing and targeting it for degradation. Surprisingly, despite binding to other pre-microRNAs (pre-miRNAs), only pre-let-7 is efficiently uridylated by TuT4. Thus, we hypothesized the existence of substrate-specific cofactors that stimulate Lin28a-mediated pre-let-7 uridylation or restrict its functionality on non-let-7 pre-miRNAs. Through RNA pull-downs coupled with quantitative mass spectrometry, we identified the E3 ligase Trim25 as an RNA-specific cofactor for Lin28a/TuT4-mediated uridylation. We show that Trim25 binds to the conserved terminal loop (CTL) of pre-let-7 and activates TuT4, allowing for more efficient Lin28a-mediated uridylation. These findings reveal that protein-modifying enzymes, only recently shown to bind RNA, can guide the function of canonical ribonucleoprotein (RNP) complexes in cis, thereby providing an additional level of specificity.

  14. Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation

    Directory of Open Access Journals (Sweden)

    Nila Roy Choudhury


    Full Text Available RNA binding proteins have thousands of cellular RNA targets and often exhibit opposite or passive molecular functions. Lin28a is a conserved RNA binding protein involved in pluripotency and tumorigenesis that was previously shown to trigger TuT4-mediated pre-let-7 uridylation, inhibiting its processing and targeting it for degradation. Surprisingly, despite binding to other pre-microRNAs (pre-miRNAs, only pre-let-7 is efficiently uridylated by TuT4. Thus, we hypothesized the existence of substrate-specific cofactors that stimulate Lin28a-mediated pre-let-7 uridylation or restrict its functionality on non-let-7 pre-miRNAs. Through RNA pull-downs coupled with quantitative mass spectrometry, we identified the E3 ligase Trim25 as an RNA-specific cofactor for Lin28a/TuT4-mediated uridylation. We show that Trim25 binds to the conserved terminal loop (CTL of pre-let-7 and activates TuT4, allowing for more efficient Lin28a-mediated uridylation. These findings reveal that protein-modifying enzymes, only recently shown to bind RNA, can guide the function of canonical ribonucleoprotein (RNP complexes in cis, thereby providing an additional level of specificity.

  15. Nestin expression associates with poor prognosis and triple negative phenotype in locally advanced (T4 breast cancer

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    F. Piras


    Full Text Available Nestin, an intermediate filament protein, has traditionally been noted for its importance as a neural stem cell marker. However, in recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients’ outcome. Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5-years survival (P=0.02 and with borderline significance at 10-years of survival (P=0.05 in T4 breast cancer patients. On the basis of these observations, we speculate that nestin expression may characterize tumours with an aggressive clinical behavior, suggesting that the presence of nestin in tumoral cells and vessels may be considered an important factor that leads to a poor prognosis. Further studies are awaited to define the biological role of nestin in the etiology of these subgroups of breast cancers.

  16. Determinants of prognosis in breast cancer patients with tumor involvement of the skin (pT4b).

    NARCIS (Netherlands)

    Wieland, A.W.; Louwman, M.W.; Voogd, A.C.; Beek, M.W. van; Vreugdenhil, G.R.; Roumen, R.M.H.


    Determinants of prognosis were studied in patients with breast cancer with histologically proven tumor extension to the skin without clinical evidence of distant metastases (i.e., pT4b N0-3 M0). Data were collected retrospectively on 77 consecutive patients diagnosed in one community teaching hospit

  17. Cryptic t(4;11) encoding MLL-AF4 due to insertion of 5' MLL sequences in chromosome 4

    NARCIS (Netherlands)

    von Bergh, A; Gargallo, P; De Prijck, B; Vranckx, H; Marschalek, R; Larripa, I; Kluin, P; Schuuring, E; Hagemeijer, A


    The t(4;11) translocation is the cytogenetic hallmark of a subset of acute lymphoblastic leukemias characterized by pro-B immunophenotype and a dismal prognosis. This translocation fuses the MLL gene on chromosome band 11q23 and the AF4 gene on 4q21, resulting in the expression of fusion transcripts

  18. Esophageal motion characteristics in thoracic esophageal cancer: Impact of clinical stage T4 versus stages T1-T3

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    Yuta Kobayashi, MS


    Conclusions: The EM and the ITV margins in cT4 were significantly smaller than those in cT1-T3. The NM and the ITV margins of abdominal LNs were much larger than those of cervicothoracic LNs and the esophagus. In clinical radiation therapy planning for esophageal cancer, we should take cT stage into consideration.

  19. Cryo-EM structure of the bacteriophage T4 portal protein assembly at near-atomic resolution. (United States)

    Sun, Lei; Zhang, Xinzheng; Gao, Song; Rao, Prashant A; Padilla-Sanchez, Victor; Chen, Zhenguo; Sun, Siyang; Xiang, Ye; Subramaniam, Sriram; Rao, Venigalla B; Rossmann, Michael G


    The structure and assembly of bacteriophage T4 has been extensively studied. However, the detailed structure of the portal protein remained unknown. Here we report the structure of the bacteriophage T4 portal assembly, gene product 20 (gp20), determined by cryo-electron microscopy (cryo-EM) to 3.6 Å resolution. In addition, analysis of a 10 Å resolution cryo-EM map of an empty prolate T4 head shows how the dodecameric portal assembly interacts with the capsid protein gp23 at the special pentameric vertex. The gp20 structure also verifies that the portal assembly is required for initiating head assembly, for attachment of the packaging motor, and for participation in DNA packaging. Comparison of the Myoviridae T4 portal structure with the known portal structures of φ29, SPP1 and P22, representing Podo- and Siphoviridae, shows that the portal structure probably dates back to a time when self-replicating microorganisms were being established on Earth.

  20. Determinants of prognosis in breast cancer patients with tumor involvement of the skin (pT4b).

    NARCIS (Netherlands)

    Wieland, A.W.; Louwman, M.W.; Voogd, A.C.; Beek, M.W. van; Vreugdenhil, G.R.; Roumen, R.M.H.


    Determinants of prognosis were studied in patients with breast cancer with histologically proven tumor extension to the skin without clinical evidence of distant metastases (i.e., pT4b N0-3 M0). Data were collected retrospectively on 77 consecutive patients diagnosed in one community teaching

  1. A bacteriophage T4 in vitro system to clone long DNA molecules. Final report, June 1, 1990--January 31, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Rao, V.B.


    A summary is presented of the following objectives: development of a bacteriophage T4 in vitro system, and techniques to clone long segments of foreign DNA; development of a giant prohead DNA packaging system that could potentially be used to clone even a megabase size DNA; and development of techniques to rapidly map the cloned DNA inserts.

  2. CRISPR/Cas9-mediated phage resistance is not impeded by the DNA modifications of phage T4.

    Directory of Open Access Journals (Sweden)

    Stephanie J Yaung

    Full Text Available Bacteria rely on two known DNA-level defenses against their bacteriophage predators: restriction-modification and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR-CRISPR-associated (Cas systems. Certain phages have evolved countermeasures that are known to block endonucleases. For example, phage T4 not only adds hydroxymethyl groups to all of its cytosines, but also glucosylates them, a strategy that defeats almost all restriction enzymes. We sought to determine whether these DNA modifications can similarly impede CRISPR-based defenses. In a bioinformatics search, we found naturally occurring CRISPR spacers that potentially target phages known to modify their DNA. Experimentally, we show that the Cas9 nuclease from the Type II CRISPR system of Streptococcus pyogenes can overcome a variety of DNA modifications in Escherichia coli. The levels of Cas9-mediated phage resistance to bacteriophage T4 and the mutant phage T4 gt, which contains hydroxymethylated but not glucosylated cytosines, were comparable to phages with unmodified cytosines, T7 and the T4-like phage RB49. Our results demonstrate that Cas9 is not impeded by N6-methyladenine, 5-methylcytosine, 5-hydroxymethylated cytosine, or glucosylated 5-hydroxymethylated cytosine.

  3. Cellular mechanisms of reduced sarcoplasmic reticulum Ca2+ content in L-thyroxin-induced rat ventricular hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Lai-jing SONG; Guan-lei WANG; Jie LIU; Qin-ying QIU; Jing-hua OU; Yong-yuan GUAN


    Aim:To examine how the sarcoplasmic reticulum (SR) Ca2+ content changes and the underlying mechanism in L-thyroxin-induced cardiac hypertrophy. Methods:Echocardiography was used to confirm the establishment of the cardiac hypertro-phy model. The confocal microscopy and fluorescent indicator Fluo-3 was ap-plied to examine the intracellular Ca2+ concentration ([Ca2+]I), the Ca2+ sparks, and the caffeine-induced Ca2+ transient in freshly isolated cardiac ventricular myocytes. The activity of sarcolemmal and SR Ca2+-ATPase 2a (SERCA2a) in the ventricular tissue was also measured, respectively. Results:L-thyroxin (1 mg/kg injection for 10 d) induces left ventricular cardiac hypertrophy with normal myocardial function. The decreased caffeine-induced Ca2+ transient in the Ca2+-free solution was detected. The spontaneous Ca2+ sparks in hypertrophied myocytes occurred more frequently than in normal cells, with similar duration and spatial spread, but smaller amplitude. Then the basal [Ca2+]I increase was observed in quiescent left ventricular myocytes from hyperthyroidism rats. The activity of sarcolemmal and SR Ca2+-ATPase was decreased in the hypertrophied ventricle tissue. Conclusion:The results suggested that the reduced SR Ca2+ content may be associated with an increased Ca2+ leak and reduced SERCA2a activity, contributing to abnormal intracellular Ca2+ handling during hypertrophy in hyperthyroidism rats.

  4. Comparison of only T3 and T3-T4 sympathectomy for axillary hyperhidrosis regarding treatment effect and compensatory sweating. (United States)

    Yuncu, Gökhan; Turk, Figen; Ozturk, Gökhan; Atinkaya, Cansel


    Patients diagnosed with axillary hyperhidrosis can face psychosocial issues that can ultimately hinder their quality of life both privately and socially. The routine treatment for axillary hyperhidrosis is T3-T4 sympathectomy, but compensatory sweating is a serious side effect that is commonly seen with this approach. This study was designed to evaluate whether a T3 sympathectomy was effective for the treatment of axillary hyperhidrosis and whether this treatment led to less compensatory sweating than T3-T4 sympathectomies among our 60-patient population. One hundred and twenty endoscopic thoracic sympathectomies were performed on 60 patients who had axillary hyperhidrosis. The sympathectomies were accomplished by means of a single-lumen endotracheal tube and a single port. The axillary hyperhidrosis patients were randomly divided into two groups with 17 patients in Group 1 undergoing T3-T4 sympathectomies and 43 in Group 2 undergoing only T3 sympathectomies. We analysed the data associated with the resolution of axillary hyperhidrosis, the degree of patient satisfaction with the surgical outcome and the quality of life in parallel with compensatory sweating after the procedure as reported by the patient and confirmed by the examiner. Moreover, the results were compared statistically. No statistically significant difference was observed between the groups based on age (P=0.56), gender (P=0.81), duration of the surgery (P=0.35) or postoperative satisfaction levels (P=0.45). However, the incidence and degree of compensatory sweating were lower in the T3 group than the T3-T4 group at the 1-year follow-up (P=0.008). T3 sympathectomy was as effective as T3-T4 sympathectomy for the treatment of axillary hyperhidrosis based on the patients' reported postoperative satisfaction, and the T3 group demonstrated lower compensatory sweating at the 1-year follow-up.

  5. The relationship of the anti-oxidant bilirubin with free thyroxine is modified by insulin resistance in euthyroid subjects.

    Directory of Open Access Journals (Sweden)

    Petronella E Deetman

    Full Text Available BACKGROUND: The strong anti-oxidative properties of bilirubin largely explain its cardioprotective effects. Insulin resistance is featured by low circulating bilirubin. Thyroid hormone affects both bilirubin generation and its biliary transport, but it is unknown whether circulating bilirubin is associated with thyroid function in euthyroid subjects. Aim is to determine relationships of bilirubin with TSH, free T4 and free T3 in euthyroid subjects without type 2 diabetes mellitus (T2DM, and to assess whether such a relationship would be modified by the degree of insulin resistance. METHODS: Total bilirubin, TSH, free T4, free T3, glucose, insulin, lipids and transaminases were measured in 1854 fasting euthyroid subjects without T2DM, recruited from the general population (PREVEND cohort. Insulin resistance was assessed by homeostasis model assessment. RESULTS: Bilirubin was positively related to free T4 (β = 0.116, P<0.001 and free T3 (β = 0.078, P = 0.001, but bilirubin was unrelated to TSH. The relationship of bilirubin with free T4 was modified by insulin resistance with a larger effect in more insulin resistant individuals (adjusted for age and sex: β = 0.043, P = 0.056 for interaction; additionally adjusted for smoking, alcohol intake, transaminases and total cholesterol (β = 0.044, P = 0.044 for interaction. The association of bilirubin with free T4 was also modified by high density lipoprotein cholesterol (age- and sex-adjusted: β = 0.040, P = 0.072. CONCLUSIONS: Low bilirubin relates to low free T4 in euthyroid non-diabetic subjects. Low normal free T4 may particularly confer low bilirubin in more insulin resistant individuals.


    Directory of Open Access Journals (Sweden)

    Sukati Saidin


    Full Text Available ASSOCIATION OF SERUM CHLOR CONTENT WITH T3/T4 HORMONEIN SCHOOL CHILDREN IN IODINE DEFICIENCY REGION.Background: The National Mapping Survey of IDD (1998 found that 7% of sub districts In Indonesia was regarded as severe endemic goitre area (TGR>30%. The high TGR prevalence, beside as a result of low iodized salt consumption (< 30 ppm, It was assumed as the effect of exposure of goitrogenic agent such as chlorine. Based on observation in Karawang sub district showed people had food habit to consume fish contaminated by insecticide used for killing milk fish predator or salted fish which had also contaminated by insecticide used during process of fish drying. Insecticide raw material consists of chlorine which can not be broken by heat or oxidation. Previous study by Gaitan E. (1986 found that chlorine component could inhibit iodine metabolism to form mono and di-iodotyrosine as precursor of T3 and T4 hormones.Objectives: The aim of this study was to find an association of serum chlorine as a reflection of chlorine consumption from daily food with T3 and T4 hormone.Methods: Research design was case control. Study was conducted in Karawang district, West Java. The subject were elementary school children in the fourth, fifth and sixth grades with positive goitre at grade I and II by palpation. Sample size was 140 children divided into two groups, case group (70 children and control group (70 children. Main data collected was chlorine consumption from daily food, serum chlorine, serum T3 and T4 hormones as well as anthropometries.Results: The result showed that chlorine consumption from food was relatively greater in case group (135.9 ugr/day than in control group (129.9 ug/day but statistically it was not significant. Serum chlorine content in case group (1 14.8 mmol/L was significantly higher than in control group (102.1 mmol/L. Serum T4 hormone in case group (7.3 ug/dl was significantly lower than in control group (9.5 ug/dl. Serum T3 hormone in

  7. Acanthamoeba genotypes T2, T4, and T11 in soil sources from El Hierro island, Canary Islands, Spain. (United States)

    Reyes-Batlle, María; Zamora-Herrera, Jonadab; Vargas-Mesa, Alejandro; Valerón-Tejera, Marco Antonio; Wagner, Carolina; Martín-Navarro, Carmen Ma; López-Arencibia, Atteneri; Sifaoui, Ines; Martínez-Carretero, Enrique; Valladares, Basilio; Piñero, José E; Lorenzo-Morales, Jacob


    The genus Acanthamoeba includes pathogenic strains which are causative agents of keratitis and encephalitis that often may end fatal in humans and other animals. In the present study, forty soil samples were collected in the island of El Hierro, Canary Islands, Spain, and checked for the presence of Acanthamoeba. Samples were cultivated onto 2 % non-nutrient agar plates seeded with a layer of heat killed Escherichia coli. Amplification by PCR and sequencing of the DF3 region of the 18S rDNA of Acanthamoeba was carried out in order to confirm morphological identification of the amoebae. Furthermore, Acanthamoeba spp. was isolated from 47.5 % of soil samples. Moreover, genotypes T2, T4, and T11 were identified in these samples. To the best of our knowledge, this is the first study to establish genotypes T2, T4, and T11 in soil sources from El Hierro island.

  8. Effect of levothyroxine on live birth rate in euthyroid women with recurrent miscarriage and TPO antibodies (T4-LIFE study)

    DEFF Research Database (Denmark)

    Vissenberg, R; van Dijk, M M; Fliers, E;


    BACKGROUND: Thyroid peroxidase antibodies (TPO-Ab) in euthyroid women are associated with recurrent miscarriage (RM) and other pregnancy complications such as preterm birth. It is unclear if treatment with levothyroxine improves pregnancy outcome. Aim To determine the effect of levothyroxine admi...... we discuss the rationale and design of the T4-LIFE study, an international multi-center randomized, double blind placebo controlled, clinical trial aimed to assess the effectiveness of levothyroxine in women with recurrent miscarriage and TPO-Ab....

  9. Co-administration of Apelin and T4 Protects Inotropic and Chronotropic Changes Occurring in Hypothyroid Rats

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    Zahra Akhondali


    Full Text Available Abstract Background: One of the most important thyroid hormone targets is the cardiovascular system. Hemodynamic changes, such as decreased resting heart rate (HR, myocardial contractility, and cardiac output, and increased diastolic pressure and systemic vascular resistance, have been observed in hypothyroid patients. Moreover, in these patients, ECG changes include sinus bradycardia and low voltage complexes (P waves or QRS complexes. Objective: This study aimed at evaluating the prophylactic effect of apelin on HR changes and QRS voltage that occur in propylthiouracil (PTU-induced hypothyroid rats. Method: In this study, 48 adult male Wistar rats weighing 170-235g were randomly divided into 6 groups: Control group (normal saline ip injection + tap water gavage; P group (PTU 0.05%, in drinking water; A group (apelin 200 µ, ip; PA group [co-administration of PTU and apelin]; PT group [co-administration of PTU + T4 (0.2 mg/g per day, gavage]; and PAT group (co-administration of PTU, apelin and T4. All experiments were performed for 28 consecutive days, and then the animals were anesthetized with an ip injection of ketamine (80 mg/kg and xylazine (12 mg/kg. Lead II electrocardiogram was recorded to calculate HR and QRS voltage. Results: Heart rate and QRS voltage increased more significantly in the hypothyroid group that consumed both apelin and T4 (201 ± 4 beat/min, 0.71 ± 0.02 mv vs. hypothyroid 145 ± 9 beat/min, 0.563 ± 0.015 mv; respectively. Conclusion: The co-administration of apelin and T4 showed a protective effect on QRS voltage and HR in PTU‑induced hypothyroid rats.

  10. Regulation of inter- and intramolecular ligation with T4 DNA ligase in the presence of polyethylene glycol.


    Hayashi, K.; NAKAZAWA, M.; Ishizaki, Y; Hiraoka, N.; Obayashi, A


    Polyethylene glycol (PEG) stimulates ligation with T4 DNA ligase. In 10% (w/v) PEG 6,000 solutions, only intermolecular ligation is enhanced by monovalent cations, while both inter- and intramolecular ligation occur without their presence. Similar stimulation was also caused by divalent cations or polyamines in the PEG 6,000 solutions. Such properties of the ligase could be applied to control the extent of inter- and intramolecular ligation. Ligation with cations or polyamines in 10% PEG 6,00...

  11. LFPy and hybrid scheme for local field potentials. CNS2014 tutorial T4: Modeling and analysis of extracellular potentials


    Hagen, Espen


    T4: Modeling and analysis of extracellular potentialsGaute Einevoll, Norwegian University of Life Sciences, Ås, NorwaySzymon Łęski (Nencki Institute of Experimental Biology, Warsaw)Espen Hagen (Norwegian University of Life Sciences, Ås)While extracellular electrical recordings have been the main workhorse in electrophysiology, the interpretation of such recordings is not trivial [1,2,3]. The recorded extracellular potentials in general stem from a complicated sum of contributions from all tr...

  12. A Raman spectroscopic study of the interaction between nucleotides and the DNA binding protein gp32 of bacteriophage T4

    NARCIS (Netherlands)

    Otto, Cornelis; de Mul, F.F.M.; Greve, Jan


    Raman spectra of the bacteriophage T4 denaturing protein gp32, its complex with the polynucleotides poly(rA), poly(dA), poly(dT), poly(rU), and poly(rC), and with the oligonucleotides (dA)8 and (dA)2, were recorded and interpreted. According to an analysis of the gp32 spectra with the reference

  13. Co-administration of Apelin and T4 Protects Inotropic and Chronotropic Changes Occurring in Hypothyroid Rats

    Energy Technology Data Exchange (ETDEWEB)

    Akhondali, Zahra; Badavi, Mohammad; Dianat, Mahin, E-mail:; Faraji, Farzaneh [Physiology Research Center and Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz (Iran, Islamic Republic of)


    One of the most important thyroid hormone targets is the cardiovascular system. Hemodynamic changes, such as decreased resting heart rate (HR), myocardial contractility, and cardiac output, and increased diastolic pressure and systemic vascular resistance, have been observed in hypothyroid patients. Moreover, in these patients, ECG changes include sinus bradycardia and low voltage complexes (P waves or QRS complexes). This study aimed at evaluating the prophylactic effect of apelin on HR changes and QRS voltage that occur in propylthiouracil (PTU)-induced hypothyroid rats. In this study, 48 adult male Wistar rats weighing 170-235g were randomly divided into 6 groups: Control group (normal saline ip injection + tap water gavage); P group (PTU 0.05%, in drinking water); A group (apelin 200 µ{sup -1}.day{sup -1}, ip); PA group [co-administration of PTU and apelin]; PT group [co-administration of PTU + T4 (0.2 mg/g per day, gavage)]; and PAT group (co-administration of PTU, apelin and T4). All experiments were performed for 28 consecutive days, and then the animals were anesthetized with an ip injection of ketamine (80 mg/kg) and xylazine (12 mg/kg). Lead II electrocardiogram was recorded to calculate HR and QRS voltage. Heart rate and QRS voltage increased more significantly in the hypothyroid group that consumed both apelin and T4 (201 ± 4 beat/min, 0.71 ± 0.02 mv vs. hypothyroid 145 ± 9 beat/min, 0.563 ± 0.015 mv; respectively). The co-administration of apelin and T4 showed a protective effect on QRS voltage and HR in PTU‑induced hypothyroid rats.

  14. 雷公藤单体T4治疗IgA肾病的实验研究

    Institute of Scientific and Technical Information of China (English)

    李江涛; 许晨; 李素; 孙向华; 马骏


    目的 研究雷公藤单体T4对实验性IgA肾病的治疗作用。方法 肝叶切除 ,4、8周后静脉注射脂多糖 (LPS)制作IgA肾病模型 ,予该模型 12 0 μg·kg- 1 ·d- 1 雷公藤单体T4腹腔注射 4周。采用考马斯亮兰法测定 2 4h尿蛋白量 ,采用ELISA法测定血清IgA FN水平 ,采用免疫荧光法检测肾小球系膜区IgA的沉积。 结果 雷公藤单体T4可抑制IgA肾病大鼠尿蛋白的产生 ,显著降低其血清IgA FN水平 ,明显减少肾小球系膜区IgA的沉积并改善其组织学病变。结论 雷公藤单体T4对该IgA肾病模型有明确治疗作用。其抑制系膜细胞增生、IgA系膜区沉积可能是通过降低血清IgA FN水平而实现的

  15. Kinetic method for the determination of traces of thyroxine by its catalytic effect on the Mn(III) metaphosphate-As(III) reaction. (United States)

    Pastor, Ferenc T; Milovanović, Gordana A; Todorović, Marija


    A new, highly sensitive and simple kinetic method for the determination of thyroxine was proposed. The method was based on the catalytic effect of thyroxine on the oxidation of As(III) by Mn(III) metaphosphate. The kinetics of the reaction was studied in the presence of orthophosphoric acid. The reaction rate was followed spectrophotometrically at 516 nm. It was established that orthophosphoric acid increased the reaction rate and that the extent of the non-catalytic reaction was extremely small. A kinetic equation was postulated and the apparent rate constant was calculated. The dependence of the reaction rate on temperature was investigated and the energy of activation and other kinetic parameters were determined. Thyroxine was determined under the optimal experimental conditions in the range 7.0 x 10(-9) to 3.0 x 10(-8) mol L(-1) with a relative standard deviation up to 6.7% and a detection limit of 2.7 x 10(-9) molL(-1). In the presence of 0.08 mol L(-1) chloride, the detection limit decreased to 6.6 x 10(-10) mol L(-1). The proposed method was applied for the determination of thyroxine in tablets. The accuracy of the method was evaluated by comparison with the HPLC method.

  16. Composite reference interval for thyroid-stimulating hormone and free thyroxine, comparison with common cutoff values, and reconsideration of subclinical thyroid disease.

    NARCIS (Netherlands)

    Ross, H.A.; Heijer, M. den; Hermus, A.R.M.M.; Sweep, C.G.J.


    BACKGROUND: Examination of the 2-dimensional probability distribution of thyroid-stimulating hormone (TSH) and free thyroxine (FT(4)) shows that the widths of the TSH and FT(4) reference intervals derived from this bivariate distribution are mutually interdependent, an aspect commonly ignored when i

  17. Evaluation of testosterone serum levels in testicular interstitial fluid under thyroxine influence; Avaliacao da testosterona no fluido intersticial testicular sob influencia da tiroxina

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Isvania Maria S. da; Pereira, Simey de L.S.; Souza, Grace Mary L.; Carvalho, Elaine F.M.B.; Catanho, Maria Teresa J. de A. [Pernambuco Univ., Recife, PE (Brazil). Dept. de Biofisica e Radiobiologia; Silveira, Maria de Fatima G. da [Pernambuco Univ., Recife, PE (Brazil). Dept. de Anatomia; Lima Filho, Guilherme L. [Universidade de Pernambuco (UPE), Nazare da Mata, PE (Brazil). Faculdade de Formacao de Professores


    The thyroid hormones possibly exert a reciprocal action between testicular steroids and Sertoli's cells during the premature period. This work aims to evaluate thyroxine effect on testosterone serum levels and in the testicular interstitial fluid (TIF) in rats. Wistar males rats, 22 days old, 80g of body weight, were induced to hyperthyroidism with thyroxine (20{mu}g/kg) in periods of 5, 10, 15 and 20 consecutive days. After the treatment the animals were weighed and sacrificed for blood and testis collection. From the blood serum and from the TIF drained from the testis were performed testes in order to obtain testosterone attached to {sup 125} I with a specific activity of 36,86 MBq/ig. The results have shown a testosterone significant lineal increase in both - serum and TIF - in the group treated with thyroxine as a time function. In the control group, testosterone levels remained low in both serum and TIF dosages. As a result, we were able to verify that the testosterone levels could be modified by thyroxine in serum and TIF. And so, it could affect luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in hypophysis. (author)

  18. 化繁为简E人E本T4原笔迹手写电脑

    Institute of Scientific and Technical Information of China (English)



  19. Maternal thyroid function at 11-13 weeks of gestation in women with hypothyroidism treated by thyroxine. (United States)

    Ashoor, Ghalia; Rotas, Michael; Maiz, Nerea; Kametas, Nikos A; Nicolaides, Kypros H


    The aim of this study in pregnant women with hypothyroidism treated by levothyroxine is to examine the interrelations between thyroid-stimulating hormone (TSH), free thyroxine (FT(4)) and free tri-iodothyronine (FT(3)), and examine whether in such patients the treatment is adequate. This was a retrospective cross-sectional study. Maternal serum concentrations of FT(3), FT(4) and TSH were measured at 11-13 weeks in 164 singleton pregnancies from women with hypothyroidism before pregnancy receiving treatment with thyroxine. The values were compared to the results in 4,318 normal singleton pregnancies. In the hypothyroid group, compared to the normal group, there was an increase in median TSH (1.990 vs. 1.007 MoM) and FT(4) (1.052 vs. 0.992 MoM) and decrease in FT(3) (0.901 vs. 0.991 MoM). Serum FT(4) was at or above the 2.5th centile in 158 (96.3%) cases but TSH was above the 97.5th centile in 48 (29.3%) and FT(3) was below the 2.5th centile in 49 (29.9%) cases. In both the hypothyroid and unaffected groups there were significant associations between TSH and FT(4), TSH and FT(3) and between FT(3) and FT(4). In a high proportion of pregnant women with hypothyroidism treated with levothyroxine there is evidence of persistent hypothyroidism because the treatment is inadequate in correcting the levels of FT(3). Copyright 2010 S. Karger AG, Basel.

  20. Potential Influence of Selenium, Copper, Zinc and Cadmium on L-Thyroxine Substitution in Patients with Hashimoto Thyroiditis and Hypothyroidism. (United States)

    Rasic-Milutinovic, Z; Jovanovic, D; Bogdanovic, G; Trifunovic, J; Mutic, J


    Background: Besides genetic factors, it is known that some trace elements, as Selenium, Copper, and Zinc are essential for thyroid gland fuction and thyroid hormone metabolism. Moreover, there were some metals effect that suggested patterns associated with overt thyroid disease. Aim of study: Hashimoto thyroiditis (HT), chronic autoimune inflamation of thyroid gland with cosequtive hipothyroidism, is common disease in Serbia, and we thought it is worthwile to explore potential effects of essential and toxic metals and metalloides on thyroid function and ability to restore euthyroid status of them. Results: This cross-sectional, case-control, study investigated the status of essential elements (Selenium,Copper,and Zinc) and toxic metals and metalloides (Al, Cr, Mn, Co, As, Cd, Sb, Ba, Be, Pb and Ni) from the blood of 22 female, patients with Hashimoto thyroiditis and overt hypothyroidism, and compared it with those of 55 female healthy persons. We tried to establish the presence of any correlation between previous mentioned elements and thyroid function in hypothyroid patients and healthy participants. Conclusions: The results of our study suggested that the blood concentration of essential trace elements, especially the ratio of Copper, and Selenium may influence directly thyroid function in patients with HT and overt hypothyroidism.Thus, our findings may have implication to life-long substitution therapy in terms of l-thyroxine dose reduction. Furthermore, for the first time, our study shown potential toxic effect of Cadmium on thyroid function in HT patients, which may implicate the dose of l-thyroxine substitution. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Total Laryngectomy Versus Larynx Preservation for T4a Larynx Cancer: Patterns of Care and Survival Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Grover, Surbhi; Swisher-McClure, Samuel [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Mitra, Nandita; Li, Jiaqi [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Cohen, Roger B. [Department of Hematology Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Ahn, Peter H.; Lukens, John N. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Chalian, Ara A.; Weinstein, Gregory S.; O' Malley, Bert W. [Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Lin, Alexander, E-mail: [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)


    Purpose: To examine practice patterns and compare survival outcomes between total laryngectomy (TL) and larynx preservation chemoradiation (LP-CRT) in the setting of T4a larynx cancer, using a large national cancer registry. Methods and Materials: Using the National Cancer Database, we identified 969 patients from 2003 to 2006 with T4a squamous cell larynx cancer receiving definitive treatment with either initial TL plus adjuvant therapy or LP-CRT. Univariate and multivariable logistic regression were used to assess predictors of undergoing surgery. Survival outcomes were compared using Kaplan-Meier and propensity score–adjusted and inverse probability of treatment–weighted Cox proportional hazards methods. Sensitivity analyses were performed to account for unmeasured confounders. Results: A total of 616 patients (64%) received LP-CRT, and 353 (36%) received TL. On multivariable logistic regression, patients with advanced nodal disease were less likely to receive TL (N2 vs N0, 26.6% vs 43.4%, odds ratio [OR] 0.52, 95% confidence interval [CI] 0.37-0.73; N3 vs N0, 19.1% vs 43.4%, OR 0.23, 95% CI 0.07-0.77), whereas patients treated in high case-volume facilities were more likely to receive TL (46.1% vs 31.5%, OR 1.78, 95% CI 1.27-2.48). Median survival for TL versus LP was 61 versus 39 months (P<.001). After controlling for potential confounders, LP-CRT had inferior overall survival compared with TL (hazard ratio 1.31, 95% CI 1.10-1.57), and with the inverse probability of treatment–weighted model (hazard ratio 1.25, 95% CI 1.05-1.49). This survival difference was shown to be robust on additional sensitivity analyses. Conclusions: Most patients with T4a larynx cancer receive LP-CRT, despite guidelines suggesting TL as the preferred initial approach. Patients receiving LP-CRT had more advanced nodal disease and worse overall survival. Previous studies of (non-T4a) locally advanced larynx cancer showing no difference in survival between LP-CRT and TL may not

  2. Partial Complementation of the UV Sensitivity of Deinococcus Radiodurans Excision Repair Mutants by the Cloned denv Gene of Bacteriophage T4 (United States)


    ligated with the denV gene containing fragment from pTACdenV using T4 DNA ligase . T4 DNA ligase catalyzes the formation of phosphodiester bonds between...MgClj, lOmM DTT, 1 ug DNA, 0. 5mM ATP, 50 ug/ml BSA and 1 U T4 DNA ligase . Incubation was at 15°C overnight. Transformation of E. coli with DNA

  3. A cobalt oxyhydroxide nanoflake-based nanoprobe for the sensitive fluorescence detection of T4 polynucleotide kinase activity and inhibition (United States)

    Cen, Yao; Yang, Yuan; Yu, Ru-Qin; Chen, Ting-Ting; Chu, Xia


    Phosphorylation of nucleic acids with 5'-OH termini catalyzed by polynucleotide kinase (PNK) is an inevitable process and has been implicated in many important cellular events. Here, we found for the first time that there was a significant difference in the adsorbent ability of cobalt oxyhydroxide (CoOOH) nanoflakes between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), which resulted in the fluorescent dye-labeled dsDNA still retaining strong fluorescence emission, while the fluorescence signal of ssDNA was significantly quenched by CoOOH nanoflakes. Based on this discovery, we developed a CoOOH nanoflake-based nanoprobe for the fluorescence sensing of T4 PNK activity and its inhibition by combining it with λ exonuclease cleavage reaction. In the presence of T4 PNK, dye-labeled dsDNA was phosphorylated and then cleaved by λ exonuclease to generate ssDNA, which could adsorb on the CoOOH nanoflakes and whose fluorescence was quenched by CoOOH nanoflakes. Due to the high quenching property of CoOOH nanoflakes as an efficient energy acceptor, a sensitive and selective sensing approach with satisfactory performance for T4 PNK sensing in a complex biological matrix has been successfully constructed and applied to the screening of inhibitors. The developed approach may potentially provide a new platform for further research, clinical diagnosis, and drug discovery of nucleotide kinase related diseases.Phosphorylation of nucleic acids with 5'-OH termini catalyzed by polynucleotide kinase (PNK) is an inevitable process and has been implicated in many important cellular events. Here, we found for the first time that there was a significant difference in the adsorbent ability of cobalt oxyhydroxide (CoOOH) nanoflakes between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), which resulted in the fluorescent dye-labeled dsDNA still retaining strong fluorescence emission, while the fluorescence signal of ssDNA was significantly quenched by Co

  4. Preclinical Development of an anti-5T4 Antibody-Drug Conjugate: Pharmacokinetics in Mice, Rats, and NHP and Tumor/Tissue Distribution in Mice. (United States)

    Leal, Mauricio; Wentland, JoAnn; Han, Xiaogang; Zhang, Yanhua; Rago, Brian; Duriga, Nicole; Spriggs, Franklin; Kadar, Eugene; Song, Wei; McNally, James; Shakey, Quazi; Lorello, Leslie; Lucas, Judy; Sapra, Puja


    The pharmacokinetics of an antibody (huA1)-drug (auristatin microtubule disrupting MMAF) conjugate, targeting 5T4-expressing cells, were characterized during the discovery and development phases in female nu/nu mice and cynomolgus monkeys after a single dose and in S-D rats and cynomolgus monkeys from multidose toxicity studies. Plasma/serum samples were analyzed using an ELISA-based method for antibody and conjugate (ADC) as well as for the released payload using an LC-MS/MS method. In addition, the distribution of the Ab, ADC, and released payload (cys-mcMMAF) was determined in a number of tissues (tumor, lung, liver, kidney, and heart) in two tumor mouse models (H1975 and MDA-MB-361-DYT2 models) using similar LBA and LC-MS/MS methods. Tissue distribution studies revealed preferential tumor distribution of cys-mcMMAF and its relative specificity to the 5T4 target containing tissue (tumor). Single dose studies suggests lower CL values at the higher doses in mice, although a linear relationship was seen in cynomolgus monkeys at doses from 0.3 to 10 mg/kg with no evidence of TMDD. Evaluation of DAR (drug-antibody ratio) in cynomolgus monkeys (at 3 mg/kg) indicated that at least half of the payload was still on the ADC 1 to 2 weeks after IV dosing. After multiple doses, the huA1 and conjugate data in rats and monkeys indicate that exposure (AUC) increases with increasing dose in a linear fashion. Systemic exposure (as assessed by Cmax and AUC) of the released payload increased with increasing dose, although exposure was very low and its pharmacokinetics appeared to be formation rate limited. The incidence of ADA was generally low in rats and monkeys. We will discuss cross species comparison, relationships between the Ab, ADC, and released payload exposure after multiple dosing, and insights into the distribution of this ADC with a focus on experimental design as a way to address or bypass apparent obstacles and its integration into predictive models.

  5. Radical nephroureterectomy for pathologic T4 upper tract urothelial cancer: can oncologic outcomes be improved with multimodality therapy?

    Directory of Open Access Journals (Sweden)

    Ramy F. Youssef


    Full Text Available Purpose To report the outcomes of patients with pathologic T4 UTUC and investigate the potential impact of peri-operative chemotherapy combined with radical nephroureterectomy (RNU and regional lymph node dissection (LND on oncologic outcomes. Materials and Methods Patients with pathologic T4 UTUC were identified from the cohort of 1464 patients treated with RNU at 13 academic centers between 1987 and 2007. Oncologic outcomes were stratified according to utilization of perioperative systemic chemotherapy and regional LND as an adjunct to RNU. Results The study included 69 patients, 42 males (61% with median age 73 (range 43-98. Median follow-up was 17 months (range: 6-88. Lymphovascular invasion was found in 47 (68% and regional lymph node metastases were found in 31 (45%. Peri-operative chemotherapy was utilized in 29 (42% patients. Patients treated with peri-operative chemotherapy and RNU with LND demonstrated superior oncologic outcomes compared to those not treated by chemotherapy and/or LND during RNU (3Y-DFS: 35% vs. 10%; P = 0.02 and 3Y-CSS: 28% vs. 14%; P = 0.08. In multivariate Cox regression analysis, administration of peri-operative chemotherapy and utilization of LND during RNU was associated with lower probability of recurrence (HR: 0.4, P = 0.01, and cancer specific mortality (HR: 0.5, P = 0.06. Conclusions Pathological T4 UTUC is associated with poor prognosis. Peri-operative chemotherapy combined with aggressive surgery, including lymph node dissection, may improve oncological outcomes. Our findings support the use of aggressive multimodal treatment in patients with advanced UTUC.

  6. Reporting of T4 Genotype of Acanthamoeba Isolates in Recreational Water Sources of Gilan Province, Northern Iran

    Directory of Open Access Journals (Sweden)

    Maryam Niyyati


    Full Text Available Background: Acanthamoeba spp. is the causative agent of blindness keratitis and fatal encephalaitis. Presence of Acanthamoeba spp. in a wide variety of niches such as different water types can lead to exposure of high risk people such as contact lens wearers. The main aim of the present study was to explore the occurrence of Acanthamoeba genotypes in the recreational water sources using both morphological and molecular approaches in Gilan province, Iran.Materials and Methods: Overall, 50 samples were collected from recreational water sources including man- made and natural waters in Gilan province. Filtration and cultivation of samples was performed using non-nutrient agar. Cloning of Acanthamoeba spp. was done to eliminate bacterial and fungi contamination. PCR amplification and sequencing were performed using genus-specific primer pair. Genotype identification was based on homology analysis of 18S rRNA gene (DF3 of the obtained sequences with the available genes in the gene bank data base.Results: Out of 50 water samples, 15 (30% were positive for Acanthamoeba trophozoites and cysts according to morphological criteria. Cloning of 13 isolates (26% was done successfully. Molecular analysis of 13 Acanthamoeba strain revealed that all isolates were belonged to potentially pathogenic T4 genotype.Conclusion: T4 genotype is the main cause of Acanthamoeba-related infections. Presence of Acanthamoeba belonged to T4 genotype in recreational water sources is of concern for high risk people. Alarming sign and education to high risk people is of utmost importance to prevent such infections.

  7. Creep Properties of the As-Cast Al-A319 Alloy: T4 and T7 Heat Treatment Effects (United States)

    Erfanian-Naziftoosi, Hamid R.; Rincón, Ernesto J.; López, Hugo F.


    In this work, the creep behavior of a commercial Al-A319 alloy was investigated in the temperature range of 413 K to 533 K (140 °C to 260 °C). Tensile creep specimens in the as-cast condition and after heat treating by solid solution (T4) and by aging (T7) were tested in a stress range varying from 60 to 170 MPa. It was found that steady-state creep strain rate was significantly low in the T7 condition when compared with either the T4 or as-cast alloy conditions. As a result, the time to failure behavior considerably increased. The experimentally determined creep exponents measured from the stress-strain curves were 4 for the as-cast alloy, 7.5 in the solid solution, and 9.5 after aging. In particular, after solid solution a grain substructure was found to develop which indicated that creep in a constant subgrain structure was active, thus accounting for the n exponent of 7.5. In the aged condition, a stress threshold is considered to account for the power law creep exponent n of 9.5. Moreover, It was found that the creep activation energy values were rather similar for the alloys in the as-cast (134 kJ/mol) and T4 (146 kJ/mol) conditions. These values are close to the one corresponding to pure Al self-diffusion (143 kJ/mol). In the aged alloy, the apparent creep activation energy (202 kJ/mol) exceeded that corresponding to Al self-diffusion. This deviation in activation energy is attributed to the effect of temperature on the alloy elastic modulus. Microstructural observations using transmission electron microscopy provided further support for the various dislocation-microstructure interactions exhibited by the alloy under the investigated creep conditions and implemented heat treatments.

  8. [Effect of T4 thoracoscopic sympathectomy on 
plantar hyperhidrosis in patients with 
primary palmoplantar hyperhidrosis]. (United States)

    Xiao, Peng; Liu, Aizhong; Liu, Wenliang



  9. Investigation of the T4 and T6 heat treatment cycles of semi-solid processed aluminium alloy A356

    CSIR Research Space (South Africa)

    Moller, H


    Full Text Available and T6 heat treatment cycles of semi- solid processed aluminium alloy A356 H. Möller*,1, G. Govender1 and W.E. Stumpf2 1Materials Science and Manufacturing, CSIR, Pretoria, 0001, South Africa 2Materials Science and Metallurgical Engineering... treatments. It is shown that a decrease of the solution treatment time at 540oC from 6 hours to 1 hour does not alter the T4 or T6 tensile properties of the SSM processed A356 alloy. Slightly better impact properties are obtained with the shorter solution...

  10. Peculiarities of Crystal Structure of the Cubic System Compounds with T 4 and T 5 Space Groups (United States)

    Zolotarev, M. L.; Poplavnoi, A. S.


    We study symmetry peculiarities of crystalline compounds of a cubic system with the space groups T 4 and T 5 caused by the absence of point Wyckoff-sets in the unit cells of these groups. Due to the high multiplicity of the available Wyckoff positions, such compounds possess unit cells of complex composition. In these compounds, pseudosymmetry is realized with high probability when some group of atoms is located in positions close to the positions of higher-symmetry groups. We provide examples of crystalline compounds showing predicted specific structural features.

  11. Mutated and Bacteriophage T4 Nanoparticle Arrayed F1-V Immunogens from Yersinia pestis as Next Generation Plague Vaccines (United States)

    Tao, Pan; Mahalingam, Marthandan; Kirtley, Michelle L.; van Lier, Christina J.; Sha, Jian; Yeager, Linsey A.; Chopra, Ashok K.; Rao, Venigalla B.


    Pneumonic plague is a highly virulent infectious disease with 100% mortality rate, and its causative organism Yersinia pestis poses a serious threat for deliberate use as a bioterror agent. Currently, there is no FDA approved vaccine against plague. The polymeric bacterial capsular protein F1, a key component of the currently tested bivalent subunit vaccine consisting, in addition, of low calcium response V antigen, has high propensity to aggregate, thus affecting its purification and vaccine efficacy. We used two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, to construct new plague vaccines that provided complete protection against pneumonic plague. The NH2-terminal β-strand of F1 was transplanted to the COOH-terminus and the sequence flanking the β-strand was duplicated to eliminate polymerization but to retain the T cell epitopes. The mutated F1 was fused to the V antigen, a key virulence factor that forms the tip of the type three secretion system (T3SS). The F1mut-V protein showed a dramatic switch in solubility, producing a completely soluble monomer. The F1mut-V was then arrayed on phage T4 nanoparticle via the small outer capsid protein, Soc. The F1mut-V monomer was robustly immunogenic and the T4-decorated F1mut-V without any adjuvant induced balanced TH1 and TH2 responses in mice. Inclusion of an oligomerization-deficient YscF, another component of the T3SS, showed a slight enhancement in the potency of F1-V vaccine, while deletion of the putative immunomodulatory sequence of the V antigen did not improve the vaccine efficacy. Both the soluble (purified F1mut-V mixed with alhydrogel) and T4 decorated F1mut-V (no adjuvant) provided 100% protection to mice and rats against pneumonic plague evoked by high doses of Y. pestis CO92. These novel platforms might lead to efficacious and easily manufacturable next generation plague vaccines. PMID:23853602

  12. Thyroid stimulating immunoglobulins in Graves' disease with goitre growth, low thyroxine and increasing triiodothyronine during PTU treatment

    DEFF Research Database (Denmark)

    Hegedüs, Laszlo; Hansen, J M; Bech, K


    In 50 consecutive patients with Graves' disease treated with PTU, 7 (group 1) developed increasing goitre in spite of unmeasurable TSH. Thyroid variables were compared with those from 10 controls with an ordinary response to PTU (group 2). Serum T4 decreased in group 1 from 246 +/- 47 nmol/l (mean...

  13. Dexamethasone differentially inhibits thyroxine- or growth hormone-induced body and organ growth of Snell dwarf mice

    NARCIS (Netherlands)

    Rooman, RPA; Kuijpers, G; Gresnigt, R; Bloemen, R; Koster, JG; van Buul-Offers, SC


    Supraphysiological doses of glucocorticoids cause growth retardation in both animals and humans. Many studies have addressed the interaction of glucocorticoids with the GH/IGF system, but little is known about the effect of glucocorticoids on T-4-stimulated growth. The Snell dwarf mouse is deficient

  14. Dexamethasone differentially inhibits thyroxine- or growth hormone-induced body and organ growth of Snell dwarf mice

    NARCIS (Netherlands)

    Rooman, RPA; Kuijpers, G; Gresnigt, R; Bloemen, R; Koster, JG; van Buul-Offers, SC

    Supraphysiological doses of glucocorticoids cause growth retardation in both animals and humans. Many studies have addressed the interaction of glucocorticoids with the GH/IGF system, but little is known about the effect of glucocorticoids on T-4-stimulated growth. The Snell dwarf mouse is deficient

  15. T4SP Database 2.0: An Improved Database for Type IV Secretion Systems in Bacterial Genomes with New Online Analysis Tools

    Directory of Open Access Journals (Sweden)

    Na Han


    Full Text Available Type IV secretion system (T4SS can mediate the passage of macromolecules across cellular membranes and is essential for virulent and genetic material exchange among bacterial species. The Type IV Secretion Project 2.0 (T4SP 2.0 database is an improved and extended version of the platform released in 2013 aimed at assisting with the detection of Type IV secretion systems (T4SS in bacterial genomes. This advanced version provides users with web server tools for detecting the existence and variations of T4SS genes online. The new interface for the genome browser provides a user-friendly access to the most complete and accurate resource of T4SS gene information (e.g., gene number, name, type, position, sequence, related articles, and quick links to other webs. Currently, this online database includes T4SS information of 5239 bacterial strains. Conclusions. T4SS is one of the most versatile secretion systems necessary for the virulence and survival of bacteria and the secretion of protein and/or DNA substrates from a donor to a recipient cell. This database on virB/D genes of the T4SS system will help scientists worldwide to improve their knowledge on secretion systems and also identify potential pathogenic mechanisms of various microbial species.

  16. T4SP Database 2.0: An Improved Database for Type IV Secretion Systems in Bacterial Genomes with New Online Analysis Tools (United States)

    Han, Na; Yu, Weiwen; Qiang, Yujun


    Type IV secretion system (T4SS) can mediate the passage of macromolecules across cellular membranes and is essential for virulent and genetic material exchange among bacterial species. The Type IV Secretion Project 2.0 (T4SP 2.0) database is an improved and extended version of the platform released in 2013 aimed at assisting with the detection of Type IV secretion systems (T4SS) in bacterial genomes. This advanced version provides users with web server tools for detecting the existence and variations of T4SS genes online. The new interface for the genome browser provides a user-friendly access to the most complete and accurate resource of T4SS gene information (e.g., gene number, name, type, position, sequence, related articles, and quick links to other webs). Currently, this online database includes T4SS information of 5239 bacterial strains. Conclusions. T4SS is one of the most versatile secretion systems necessary for the virulence and survival of bacteria and the secretion of protein and/or DNA substrates from a donor to a recipient cell. This database on virB/D genes of the T4SS system will help scientists worldwide to improve their knowledge on secretion systems and also identify potential pathogenic mechanisms of various microbial species.

  17. Resveratrol given intraperitoneally does not inhibit growth of high-risk t(4;11) acute lymphoblastic leukemia cells in NOD/SCID mouse model (United States)

    The efficacy of the phytochemical resveratrol as a preventive agent against the growth of t(4;11) acute lymphoblastic leukemia (ALL) was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL line SEM. SEM cells were injected into the tail vein and engraftment was monitored by ...


    Kuznetsova, L A; Derkach, K V; Sharova, T S; Bondareva, V M; Shpakov, A O


    Under obesity, a component of metabolic syndrome (MS), macro- and microcirculation are attenuated, which is associated with abnormalities of NO-dependent cascades and leads to pathology of the cardiovascular system. Among the activators of NO-synthases (NOS), the enzymes catalyzing NO synthesis, are thyroid hormones. Since obesity and MS are characterized by reduced functions, of the thyroid gland, the replacement therapy with thyroid hormones, possessing the properties of vasodilators, is one of approached to restore functioning of the cardiovascular system. However, data on influence of thyroid hormones on NOS activity in obesity are not currently available. The aim of this work was to study the effect of four-week treatment of rats with obesity induced by high-fat diet with L-thyroxine (at a daily dose of 20 mg-kg) on functional activity of total NOS, as well as one endothelial (eNOS) and neuronal (nNOS) isoforms of the enzyme in the brain, myocardium and skeletal muscles of animals. In obese rats the decrease of thyroid hormones level, impaired glucose toleranse, and dyslipidemia were detected. In the myocardium and skeletal muscles of obese rats the activity of total NOS and eNOS was strongly decreased, whereas in the brain the activity of these enzymes was not significantly changed. Long-term treatment of obese rats with thyroxine led to a significant increase in activity of total NOS and eNOS in the myocardium and skeletal muscles and to an increase in activity of total NOS and nNOS in the brain, with the enzyme activity exceeding that in control. In healthy animals treated with thyroxine a significant increase in activity of total NOS and eNOS in the myocardium and skeletal muscles and in activity of total NOS in the brain was also eNOS in the myocardium and skeletal muscles and in activity of total NOS in the brain was also found. A significant contribution to the increasing activity of total NOS in obese rats and healthy animals treated with thyroxine

  19. Fetal Environment Is a Major Determinant of the Neonatal Blood Thyroxine Level: Results of a Large Dutch Twin Study. (United States)

    Zwaveling-Soonawala, Nitash; van Beijsterveldt, Catharina E M; Mesfum, Ertirea T; Wiedijk, Brenda; Oomen, Petra; Finken, Martijn J J; Boomsma, Dorret I; van Trotsenburg, A S Paul


    The interindividual variability in thyroid hormone function parameters is much larger than the intraindividual variability, suggesting an individual set point for these parameters. There is evidence to suggest that environmental factors are more important than genetic factors in the determination of this individual set point. This study aimed to quantify the effect of genetic factors and (fetal) environment on the early postnatal blood T4 concentration. This was a classical twin study comparing the resemblance of neonatal screening blood T4 concentrations in 1264 mono- and 2566 dizygotic twin pairs retrieved from the population-based Netherlands Twin Register. Maximum-likelihood estimates of variance explained by genetic and environmental influences were obtained by structural equation modeling in data from full-term and preterm twin pairs. In full-term infants, genetic factors explained 40%/31% of the variance in standardized T4 scores in boys/girls, and shared environment, 27%/22%. The remaining variance of 33%/47% was due to environmental factors not shared by twins. For preterm infants, genetic factors explained 34%/0% of the variance in boys/girls, shared environment 31%/57%, and unique environment 35%/43%. In very preterm twins, no significant contribution of genetic factors was observed. Environment explains a large proportion of the resemblance of the postnatal blood T4 concentration in twin pairs. Because we analyzed neonatal screening results, the fetal environment is the most likely candidate for these environmental influences. Genetic influences on the T4 set point diminished with declining gestational age, especially in girls. This may be due to major environmental influences such as immaturity and nonthyroidal illness in very preterm infants.

  20. Interaction of bacteriophage T4 and T7 single-stranded DNA-binding proteins with DNA (United States)

    Shokri, Leila; Rouzina, Ioulia; Williams, Mark C.


    Bacteriophages T4 and T7 are well-studied model replication systems, which have allowed researchers to determine the roles of many proteins central to DNA replication, recombination and repair. Here we summarize and discuss the results from two recently developed single-molecule methods to determine the salt-dependent DNA-binding kinetics and thermodynamics of the single-stranded DNA (ssDNA)-binding proteins (SSBs) from these systems. We use these methods to characterize both the equilibrium double-stranded DNA (dsDNA) and ssDNA binding of the SSBs T4 gene 32 protein (gp32) and T7 gene 2.5 protein (gp2.5). Despite the overall two-orders-of-magnitude weaker binding of gp2.5 to both forms of DNA, we find that both proteins exhibit four-orders-of-magnitude preferential binding to ssDNA relative to dsDNA. This strong preferential ssDNA binding as well as the weak dsDNA binding is essential for the ability of both proteins to search dsDNA in one dimension to find available ssDNA-binding sites at the replication fork.

  1. GalNAc-T4 putatively modulates the estrogen regulatory network through FOXA1 glycosylation in human breast cancer cells. (United States)

    Niang, Bachir; Jin, Liyuan; Chen, Xixi; Guo, Xiaohan; Zhang, Hongshuo; Wu, Qiong; Padhiar, Arshad Ahmed; Xiao, Min; Fang, Deyu; Zhang, Jianing


    GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. Most of the breast cancer subtypes are estrogen receptor positive, and hence, the estrogen pathway represents a key regulatory network. We investigated the expression of GalNAc-T4 in a panel of mammary epithelial cell lines and found its expression is associated with the estrogen status of the cells. FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. Rescuing GALNT4 expression could restore the interaction as well as the glycosylation of FOXA1. Together, these findings suggest a key role for GalNAc-T4 in the estrogen pathway through FOXA1 glycosylation.

  2. The Effects of T4 and A3/R Bacteriophages on Differentiation of Human Myeloid Dendritic Cells. (United States)

    Bocian, Katarzyna; Borysowski, Jan; Zarzycki, Michał; Pacek, Magdalena; Weber-Dąbrowska, Beata; Machcińska, Maja; Korczak-Kowalska, Grażyna; Górski, Andrzej


    Bacteriophages (phages) are viruses of bacteria. Here we evaluated the effects of T4 and A3/R bacteriophages, as well as phage-generated bacterial lysates, on differentiation of human myeloid dendritic cells (DCs) from monocytes. Neither of the phages significantly reduced the expression of markers associated with differentiation of DCs and their role in the activation of T cells (CD40, CD80, CD83, CD86, CD1c, CD11c, MHC II, PD-L1, PD-L2, TLR2, TLR4, and CCR7) and phagocytosis receptors (CD64 and DEC-205). By contrast, bacterial lysate of T4 phage significantly decreased the percentages of DEC-205- and CD1c-positive cells. The percentage of DEC-205-positive cells was also significantly reduced in DCs differentiated in the presence of lysate of A3/R phage. Thus while bacteriophages do not substantially affect differentiation of DCs, some products of phage-induced lysis of bacterial cells may influence the differentiation and potentially also some functions of DCs. Our results have important implications for phage therapy of bacterial infections because during infections monocytes recruited to the site of inflammation are an important source of inflammatory DCs.

  3. Optical tweezers studies of viral DNA packaging: Motor function and DNA confinement in Bacteriophages phi29, lambda, and T4 (United States)

    Smith, Douglas


    In the assembly of many viruses a powerful molecular motor translocates the genome into a pre-assembled capsid. We use optical tweezers to directly measure translocation of a single DNA molecule into the viral capsid. Improved techniques allow us to measure initiation and early stages of packaging. With phi29 the DNA terminal protein was found to cause large variations in the starting point of packaging. Removal of this protein results in terminal initiation, permitting more accurate assessment of motor function and DNA confinement forces. We investigated the role of electrostatic repulsion by varying ionic screening of the DNA. The observed trends are in accord with those theoretically expected considering counter-ion competition; however the forces are larger than expected in comparison with recent theories and DNA ejection measurements. We have recently succeeded in extending our methods to study two other phages: lambda and T4. These systems have unique structural and functional features, presenting an opportunity for comparative studies in this family of molecular motors. Initial measurements show that lambda and T4 translocate DNA several times faster than the phi29 motor, but are more sensitive to applied load.

  4. The effects of T4 and A3R bacteriophages on differentiation of human myeloid dendritic cells

    Directory of Open Access Journals (Sweden)

    Katarzyna Bocian


    Full Text Available Bacteriophages (phages are viruses of bacteria. Here we evaluated the effects of T4 and A3R bacteriophages, as well as phage-generated bacterial lysates, on differentiation of human myeloid dendritic cells (DCs from monocytes. Neither of the phages significantly reduced the expression of markers associated with differentiation of DCs and their role in the activation of T cells (CD40, CD80, CD83, CD86, CD1c, CD11c, MHC II, PD-L1, PD-L2, TLR2, TLR4, and CCR7 and phagocytosis receptors (CD64 and DEC-205. By contrast, bacterial lysate of T4 phage significantly decreased the percentages of DEC-205- and CD1c-positive cells. The percentage of DEC-205-positive cells was also significantly reduced in DCs differentiated in the presence of lysate of A3R phage. Thus while bacteriophages do not substantially affect differentiation of DCs, some products of phage-induced lysis of bacterial cells may influence the differentiation and potentially also some functions of DCs. Our results have important implications for phage therapy of bacterial infections because during infections monocytes recruited to the site of inflammation are an important source of inflammatory DCs.

  5. Giant Gravitons in AdS_3 x S^3 x T^4 Spacetime under Melvin Field Deformation

    CERN Document Server

    Huang, W H


    The giant graviton in the $AdS_3 \\times S^3 \\times T^4$ spacetime only exists when its angular momentum is a specific value and, moreover, it could have arbitrary size. In this paper we first apply the transformation of mixing azimuthal and internal coordinate or mixing time and internal coordinate to the 11D M-theory with a stack of M2-branes $\\bot$ M2-branes, then, through the mechanism of Kaluza-Klein reduction and a series of the T duality we obtain the corresponding background of a stack of D1-branes $\\bot$ D5-branes which, in the near-horizon limit, becomes the magnetic or electric Melvin field deformed $AdS_3 \\times S^3 \\times T^4$. We investigate the giant gravitons therein and show that some configurations whose angular momenta are within a finite region could have the fixed size and become more stable than the point-like graviton. We discuss the properties of how the electric/magnetic Melvin field will affect the size of the giant gravitons with the help of numerical analyses. We also see that the g...

  6. High occurrence of Acanthamoeba genotype T4 in soil sources from Bolívar State, Venezuela. (United States)

    Wagner, Carolina; Reyes-Batlle, María; Hernán, Aurora; Rojas, Elsy; Pérez, Gladymar; López-Arencibia, Atteneri; Sifaoui, Ines; Martínez-Carretero, Enrique; Piñero, José E; Valladares, Basilio; Lorenzo-Morales, Jacob


    Pathogenic strains of Acanthamoeba are causative agents of keratitis and encephalitis that often may end fatal in humans and other animals. In the present study, twenty-seven soil samples were collected in the Bolivar State in Venezuela and checked for the presence of Acanthamoeba. Samples were cultivated onto 2% non-nutrient agar plates seeded with a layer of heat killed E. coli. Amplification by PCR and sequencing of the DF3 region of the 18S rDNA of Acanthamoeba was carried out in order to confirm morphological identification of the amoebae. Furthermore, Acanthamoeba spp. was isolated from 51.8% of soil samples. Sequencing of the DF3 region of the 18S rDNA resulted in the identification of genotype T4 in all samples. To the best of our knowledge, this is the first report of genotype T4 in soil sources from Venezuela. Further studies should be carried out in this State and in the country in order to determine the current occurrence of Acanthamoeba in Venezuelan environments.

  7. Oral Application of T4 Phage Induces Weak Antibody Production in the Gut and in the Blood

    Directory of Open Access Journals (Sweden)

    Joanna Majewska


    Full Text Available A specific humoral response to bacteriophages may follow phage application for medical purposes, and it may further determine the success or failure of the approach itself. We present a long-term study of antibody induction in mice by T4 phage applied per os: 100 days of phage treatment followed by 112 days without the phage, and subsequent second application of phage up to day 240. Serum and gut antibodies (IgM, IgG, secretory IgA were analyzed in relation to microbiological status of the animals. T4 phage applied orally induced anti-phage antibodies when the exposure was long enough (IgG day 36, IgA day 79; the effect was related to high dosage. Termination of phage treatment resulted in a decrease of IgA again to insignificant levels. Second administration of phage induces secretory IgA sooner than that induced by the first administrations. Increased IgA level antagonized gut transit of active phage. Phage resistant E. coli dominated gut flora very late, on day 92. Thus, the immunological response emerges as a major factor determining phage survival in the gut. Phage proteins Hoc and gp12 were identified as highly immunogenic. A low response to exemplary foreign antigens (from Ebola virus presented on Hoc was observed, which suggests that phage platforms can be used in oral vaccine design.

  8. The Effects of T4 and A3/R Bacteriophages on Differentiation of Human Myeloid Dendritic Cells (United States)

    Bocian, Katarzyna; Borysowski, Jan; Zarzycki, Michał; Pacek, Magdalena; Weber-Dąbrowska, Beata; Machcińska, Maja; Korczak-Kowalska, Grażyna; Górski, Andrzej


    Bacteriophages (phages) are viruses of bacteria. Here we evaluated the effects of T4 and A3/R bacteriophages, as well as phage-generated bacterial lysates, on differentiation of human myeloid dendritic cells (DCs) from monocytes. Neither of the phages significantly reduced the expression of markers associated with differentiation of DCs and their role in the activation of T cells (CD40, CD80, CD83, CD86, CD1c, CD11c, MHC II, PD-L1, PD-L2, TLR2, TLR4, and CCR7) and phagocytosis receptors (CD64 and DEC-205). By contrast, bacterial lysate of T4 phage significantly decreased the percentages of DEC-205- and CD1c-positive cells. The percentage of DEC-205-positive cells was also significantly reduced in DCs differentiated in the presence of lysate of A3/R phage. Thus while bacteriophages do not substantially affect differentiation of DCs, some products of phage-induced lysis of bacterial cells may influence the differentiation and potentially also some functions of DCs. Our results have important implications for phage therapy of bacterial infections because during infections monocytes recruited to the site of inflammation are an important source of inflammatory DCs. PMID:27582733

  9. Phage T4 mobE promotes trans homing of the defunct homing endonuclease I-TevIII. (United States)

    Wilson, Gavin W; Edgell, David R


    Homing endonucleases are site-specific DNA endonucleases that typically function as mobile genetic elements by introducing a double-strand break (DSB) in genomes that lack the endonuclease, resulting in a unidirectional gene conversion event that mobilizes the homing endonuclease gene and flanking DNA. Here, we characterize phage T4-encoded mobE, a predicted free-standing HNH family homing endonuclease. We show that mobE is promoterless and dependent on upstream transcription for expression, and that an internal intrinsic terminator regulates mobE transcript levels. Crucially, in vivo mapping experiments revealed a MobE-dependent, strand-specific nick in the non-coding strand of the nrdB gene of phage T2. An internal deletion of the predicted HNH catalytic motif of MobE abolishes nicking, and reduces high-frequency inheritance of mobE. Sequence polymorphisms of progeny phage that inherit mobE are consistent with DSB repair pathways. Significantly, we found that mobility of the neighboring I-TevIII, a defunct homing endonuclease encoded within a group I intron interrupting the nrdB gene of phage T4, was dependent on an intact mobE gene. Thus, our data indicate that the stagnant nrdB intron and I-TevIII are mobilized in trans as a consequence of a MobE-dependent gene conversion event, facilitating persistence of genetic elements that have no inherent means of promoting their own mobility.

  10. Composition and interactions among bacterial, microeukaryotic and T4-like viral assemblages in lakes from both polar zones

    Directory of Open Access Journals (Sweden)

    Daniel eAguirre De Cárcer


    Full Text Available In this study we assess global biogeography and correlation patterns among three components of microbial life: bacteria, microeukaryotes, and T4-like myoviruses. In addition to environmental and biogeographical considerations, we have focused our study on samples from high-latitude pristine lakes from both poles, since these simple island-like ecosystems represent ideal ecological models to probe the relationships among microbial components and with the environment. Bacterial assemblages were dominated by members of the same groups found to dominate freshwater ecosystems elsewhere, and microeukaryotic assemblages were dominated by photosynthetic microalgae. Despite inter-lake variations in community composition, the overall percentages of OTUs shared among sites was remarkable, indicating that many microeukaryotic, bacterial, and viral OTUs are globally-distributed. We observed an intriguing negative correlation between bacterial and microeukaryotic diversity values. Notably, our analyses show significant global correlations between bacterial and microeukaryotic community structures, and between the phylogenetic compositions of bacterial and T4-like virus assemblages. Overall, environmental filtering emerged as the main factor driving community structures.

  11. Top-down controls on bacterial community structure: microbial network analysis of bacteria, T4-like viruses and protists. (United States)

    Chow, Cheryl-Emiliane T; Kim, Diane Y; Sachdeva, Rohan; Caron, David A; Fuhrman, Jed A


    Characterizing ecological relationships between viruses, bacteria and protists in the ocean are critical to understanding ecosystem function, yet these relationships are infrequently investigated together. We evaluated these relationships through microbial association network analysis of samples collected approximately monthly from March 2008 to January 2011 in the surface ocean (0-5 m) at the San Pedro Ocean Time series station. Bacterial, T4-like myoviral and protistan communities were described by Automated Ribosomal Intergenic Spacer Analysis and terminal restriction fragment length polymorphism of the gene encoding the major capsid protein (g23) and 18S ribosomal DNA, respectively. Concurrent shifts in community structure suggested similar timing of responses to environmental and biological parameters. We linked T4-like myoviral, bacterial and protistan operational taxonomic units by local similarity correlations, which were then visualized as association networks. Network links (correlations) potentially represent synergistic and antagonistic relationships such as viral lysis, grazing, competition or other interactions. We found that virus-bacteria relationships were more cross-linked than protist-bacteria relationships, suggestive of increased taxonomic specificity in virus-bacteria relationships. We also found that 80% of bacterial-protist and 74% of bacterial-viral correlations were positive, with the latter suggesting that at monthly and seasonal timescales, viruses may be following their hosts more often than controlling host abundance.

  12. Isolation and Genomic Characterization of the T4-Like Bacteriophage PM2 Infecting Pectobacterium carotovorum subsp. carotovorum. (United States)

    Lim, Jeong-A; Lee, Dong Hwan; Heu, Sunggi


    In order to control Pectobacterium carotovorum subsp. carotovorum, a novel virulent bacteriophage PM2 was isolated. Bacteriophage PM2 can infect 48% of P. carotovorum subsp. carotovorum and 78% of P. carotovorum subsp. brasilliensis but none of atrosepticum, betavasculorum, odoriferum and wasabiae isolates had been infected with PM2. PM2 phage belongs to the family Myoviridae, and contains a large head and contractile tail. It has a 170,286 base pair genome that encodes 291 open reading frames (ORFs) and 12 tRNAs. Most ORFs in bacteriophage PM2 share a high level of homology with T4-like phages including IME08, RB69, and JS98. Phylogenetic analysis based on the amino acid sequence of terminase large subunits confirmed that PM2 is classified as a T4-like phage. It contains no integrase- or no repressor-coding genes related to the lysogenic cycle, and lifestyle prediction using PHACT software suggested that PM2 is a virulent bacteriophage.

  13. Isolation and Genomic Characterization of the T4-Like Bacteriophage PM2 Infecting Pectobacterium carotovorum subsp. carotovorum

    Directory of Open Access Journals (Sweden)

    Jeong-A Lim


    Full Text Available In order to control Pectobacterium carotovorum subsp. carotovorum, a novel virulent bacteriophage PM2 was isolated. Bacteriophage PM2 can infect 48% of P. carotovorum subsp. carotovorum and 78% of P. carotovorum subsp. brasilliensis but none of atrosepticum, betavasculorum, odoriferum and wasabiae isolates had been infected with PM2. PM2 phage belongs to the family Myoviridae, and contains a large head and contractile tail. It has a 170,286 base pair genome that encodes 291 open reading frames (ORFs and 12 tRNAs. Most ORFs in bacteriophage PM2 share a high level of homology with T4-like phages including IME08, RB69, and JS98. Phylogenetic analysis based on the amino acid sequence of terminase large subunits confirmed that PM2 is classified as a T4-like phage. It contains no integrase- or no repressor-coding genes related to the lysogenic cycle, and lifestyle prediction using PHACT software suggested that PM2 is a virulent bacteriophage.

  14. Structure and Biophysical Properties of a Triple-Stranded Beta-Helix Comprising the Central Spike of Bacteriophage T4. (United States)

    Buth, Sergey A; Menin, Laure; Shneider, Mikhail M; Engel, Jürgen; Boudko, Sergei P; Leiman, Petr G


    Gene product 5 (gp5) of bacteriophage T4 is a spike-shaped protein that functions to disrupt the membrane of the target cell during phage infection. Its C-terminal domain is a long and slender β-helix that is formed by three polypeptide chains wrapped around a common symmetry axis akin to three interdigitated corkscrews. The folding and biophysical properties of such triple-stranded β-helices, which are topologically related to amyloid fibers, represent an unsolved biophysical problem. Here, we report structural and biophysical characterization of T4 gp5 β-helix and its truncated mutants of different lengths. A soluble fragment that forms a dimer of trimers and that could comprise a minimal self-folding unit has been identified. Surprisingly, the hydrophobic core of the β-helix is small. It is located near the C-terminal end of the β-helix and contains a centrally positioned and hydrated magnesium ion. A large part of the β-helix interior comprises a large elongated cavity that binds palmitic, stearic, and oleic acids in an extended conformation suggesting that these molecules might participate in the folding of the complete β-helix.

  15. Structure and Biophysical Properties of a Triple-Stranded Beta-Helix Comprising the Central Spike of Bacteriophage T4

    Directory of Open Access Journals (Sweden)

    Sergey A. Buth


    Full Text Available Gene product 5 (gp5 of bacteriophage T4 is a spike-shaped protein that functions to disrupt the membrane of the target cell during phage infection. Its C-terminal domain is a long and slender β-helix that is formed by three polypeptide chains wrapped around a common symmetry axis akin to three interdigitated corkscrews. The folding and biophysical properties of such triple-stranded β-helices, which are topologically related to amyloid fibers, represent an unsolved biophysical problem. Here, we report structural and biophysical characterization of T4 gp5 β-helix and its truncated mutants of different lengths. A soluble fragment that forms a dimer of trimers and that could comprise a minimal self-folding unit has been identified. Surprisingly, the hydrophobic core of the β-helix is small. It is located near the C-terminal end of the β-helix and contains a centrally positioned and hydrated magnesium ion. A large part of the β-helix interior comprises a large elongated cavity that binds palmitic, stearic, and oleic acids in an extended conformation suggesting that these molecules might participate in the folding of the complete β-helix.

  16. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia (United States)

    Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W.; Marschalek, Rolf; Menéndez, Pablo


    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a “multiple-and-sequential-hit” model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one “big-hit” might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models. PMID:26463423

  17. T4 test (United States)

    ... an overactive thyroid Symptoms of an underactive thyroid Hypopituitarism (the pituitary gland does not produce enough of ... thyroiditis (Hashimoto disease) Goiter - simple Graves disease Hyperthyroidism Hypopituitarism Hypothalamus Hypothyroidism Kwashiorkor T3 test Thyrotoxic periodic paralysis ...

  18. t4 Workshop Report* (United States)

    Kleensang, Andre; Maertens, Alexandra; Rosenberg, Michael; Fitzpatrick, Suzanne; Lamb, Justin; Auerbach, Scott; Brennan, Richard; Crofton, Kevin M.; Gordon, Ben; Fornace, Albert J.; Gaido, Kevin; Gerhold, David; Haw, Robin; Henney, Adriano; Ma’ayan, Avi; McBride, Mary; Monti, Stefano; Ochs, Michael F.; Pandey, Akhilesh; Sharan, Roded; Stierum, Rob; Tugendreich, Stuart; Willett, Catherine; Wittwehr, Clemens; Xia, Jianguo; Patton, Geoffrey W.; Arvidson, Kirk; Bouhifd, Mounir; Hogberg, Helena T.; Luechtefeld, Thomas; Smirnova, Lena; Zhao, Liang; Adeleye, Yeyejide; Kanehisa, Minoru; Carmichael, Paul; Andersen, Melvin E.; Hartung, Thomas


    Summary Despite wide-spread consensus on the need to transform toxicology and risk assessment in order to keep pace with technological and computational changes that have revolutionized the life sciences, there remains much work to be done to achieve the vision of toxicology based on a mechanistic foundation. A workshop was organized to explore one key aspect of this transformation – the development of Pathways of Toxicity (PoT) as a key tool for hazard identification based on systems biology. Several issues were discussed in depth in the workshop: The first was the challenge of formally defining the concept of a PoT as distinct from, but complementary to, other toxicological pathway concepts such as mode of action (MoA). The workshop came up with a preliminary definition of PoT as “A molecular definition of cellular processes shown to mediate adverse outcomes of toxicants”. It is further recognized that normal physiological pathways exist that maintain homeostasis and these, sufficiently perturbed, can become PoT. Second, the workshop sought to define the adequate public and commercial resources for PoT information, including data, visualization, analyses, tools, and use-cases, as well as the kinds of efforts that will be necessary to enable the creation of such a resource. Third, the workshop explored ways in which systems biology approaches could inform pathway annotation, and which resources are needed and available that can provide relevant PoT information to the diverse user communities. PMID:24127042

  19. Serum 25-Hydroxyvitamin D and Parathyroid Hormone Levels in Non-Lactating Women with Post-Partum Thyroiditis: The Effect of L-Thyroxine Treatment. (United States)

    Krysiak, Robert; Kowalska, Beata; Okopien, Bogusław


    Vitamin D deficiency seems to be implicated in the onset and progression of some autoimmune disorders. No previous study has investigated vitamin D homeostasis in post-partum thyroiditis. We compared 25-hydroxyvitamin D and parathyroid hormone (PTH) levels between four groups of non-lactating women who gave birth within 12 months before the beginning of the study: hypothyroid women with post-partum thyroiditis (group A; n = 14), euthyroid females with post-partum thyroiditis (group B; n = 14), women with non-autoimmune hypothyroidism (group C; n = 16) and healthy euthyroid females without thyroid autoimmunity (group D; n = 15). In the second part of the study, groups A and C were treated for 6 months with L-thyroxine. Serum levels of 25-hydroxyvitamin D were lower, while PTH higher in patients with post-partum thyroiditis than in patients without thyroid autoimmunity. They were also lower (25-hydroxyvitamin D) or higher (PTH) in group A than in group B, as well as in group C in comparison with group D. L-thyroxine treatment increased 25-hydroxyvitamin D and reduced PTH levels only in hypothyroid women with post-partum thyroiditis. Baseline levels of 25-hydroxyvitamin D correlated with thyroid antibody titres, thyroid function and circulating PTH levels, while the effect of L-thyroxine on serum levels of this vitamin correlated with the changes in thyroid antibody titres and PTH levels. The results of our study suggest the association of vitamin D status with post-partum thyroiditis and L-thyroxine treatment of this disorder.

  20. Effects of Long-Term Low-Level Radiofrequency Radiation Exposure on Rats. Volume 6. Hematological, Serum Chemistry, Thyroxine, and Protein Electrophoresis Evaluations. (United States)


    111I. 11 MICROCOPY RESOLUTION TESI CHART i ~ ~ ~ ~ ~ ~ ~ ~ ~ A N... DS................. ...".... , II I - I Reort USAFSAM-TR-84-2 EFFECTS OF LONG-TERM...obstruction, and resolving internal hemorrhage. The total levels are decreased in cases of bone-marrow-depression anemia . The direct and indirect...VIR" 4 THYROXINE Elevated contents of serum cholestrol and triglycerides and a mild normochromic, norioocytic anemia are nonspecific traits suggestive

  1. Clinical evaluation of systemic inflammatory response syndrome (SIRS) in advanced lung cancer (T3 and T4) with surgical resection. (United States)

    Iwasaki, Akinori; Shirakusa, Takayuki; Maekawa, Takafumi; Enatsu, Sotarou; Maekawa, Shinichi


    The systemic inflammatory response syndrome (SIRS) is well known to occur in patients who have suffered organ damage or trauma, or undergone surgery. SIRS provides useful information in patients with morbidity after surgery. To date, there has been no report of SIRS after surgery in patients with lung cancer. Therefore, based on this new concept of the syndrome, we review here a series of T3 and T4 NSCLC patients who underwent extended resection at our hospital, and attempt to identify the value and correlation of SIRS in predicting the morbidity of such patients. We retrospectively reviewed the patients with NSCLC treated at our hospital between January 1994 and August 2003. Among these 720 patients, a curative approach was attempted in 144 with advanced stage (T3, 100; T4, 44) cancer. The patients were consequently divided into three groups (G1, negative or less than 3 days in SIRS following surgery; G2, less than 7 days; G3, continued over 7 days). Pre- or peri-operative factors were evaluated, and the 5-year survival rates were analyzed. Post-operative morbidity was also compared between the three groups in association with SIRS. Pre-operative counts of WBC were 8848.28+/-3879.21/microl in G3 compared with 7383.33+/-3132.98/microl in G2 and 6778.31+/-3184.89/microl in G1. Values in G3 were significantly higher than those in the other groups (PSIRS after lung surgery was associated with high levels in WBC and low %FEV1. Post-operative morbidity such as bronchial fistula or ARDS were more frequent in the G3 and G2 groups than in G1. The 1-year survival was as follows; G1, 75.4%; G2, 47.9%; G3, 38.1%. Overall 5-year survival rate for NSCLC with T3 and T4 was 32.2%, and the difference between G3 and the other groups in terms of survival was statistically significant (PSIRS have been associated with post-operative complications and survival in NSCLC. Surgical candidates should be carefully according to the predicting factor of SIRS.

  2. High-molecular-weight DNA and the sedimentation coefficient: a new perspective based on DNA from T7 bacteriophage and two novel forms of T4 bacteriophage. (United States)

    Clark, R W; Wever, G H; Wiberg, J S


    The DNA molecules from T7 bacteriophage and a recently obtained mutant form of T4D were studied. The DNA of this T4 mutant contains cytosine in place of all of the glucosylated hydroxymethylcytosines normally present in T4. Molecular weights were measured with an electron microscope technique, and sedimentation coefficients were determined in isokinetic sucrose gradients. T7 DNA was found to have an Mr of 26.5 x 10(6). The T4 mutant, which we have termed T4c, produces two distinct phage head and DNA size clases. DNA from the standard heads (T4c DNA) has an Mr of 114.9 x 10(6), and DNA from the petite heads (T4cp DNA) has an Mr of 82.9 x 10(6). This enabled the derivation of an equation of sedimentation coefficient at zero concentration corrected to water at 20 degrees C versus Mr for the molecular weight range of 25 x 10(6) to 115 x 10(6) that is based solely on cytosine-containing DNA standards, thereby avoiding possible anomalies introduced by the glucosylation and hydroxymethylation of cytosine. The theory of Gray et al. provided the best description of the sedimentation coefficient versus Mr relationship, based on the sedimentation coefficients and the molecular weights of the three DNA standards and other evidence.

  3. Effect of vitamin C in pineapple rind (Ananas comosus L. Merr on thyroxine hormone and anti stress on broilers in tropical region

    Directory of Open Access Journals (Sweden)

    Syahruddin E


    Full Text Available This study was aimed to determine the right level of vitamin C in extracted pineapple rind to prevent heat stress effects so it does not interfere with the performance of broiler chickens. This study was done in a series of field experiments. Experiments in the field/cage was biological test of the effect of vitamin C from pineapple rind on production responses (percentage of body weight gain and carcass and physiological responses (thyroxine hormone levels in broiler chicken aged 3 weeks as many as 360 of Strain Arbor acress. The basic design used was CRD 3 x 4 factorial models and 3 replications with 10 chickens for each box, as factor 1: Room temperature (21 : 27 and 33ºC, and factor II: level of vitamin C in the pineapple rind (0:500:1000 and 1500 ppm. The data obtained were statistically analyzed using SAS program package, and if it showed any significant effect then followed by Duncans test/DMRT. Variables measured were body weight gain, carcass percentage and levels of thyroxine hormone of broiler. Results showed that addition of pineapple rind containing 500 ppm vitamin C in the drinking water reduced heat stress in chicken that were kept at temperature of 27ºC, while at 33ºC needed 1000 ppm vitamin C. Both treatments increase level of thyroxine hormone, produce weight gain equal to control, more over, there was no effect on the percentage of carcasses.

  4. Propranolol and verapamil inhibit mRNA expression of RyR2 and SERCA in L-thyroxin-induced rat ventricular hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Xiao-dong WU; De-zai DAI; Qiu-pin ZHANG; Feng GAO


    AIM: To study the alteration in the mRNA level of cardiac ryanodine receptor 2 (RyR2) and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) in L-thyroxin-induced hypertrophy. METHODS: L-thyroxin (500 g/kg) daily was injected for 10 d. RT-PCR was used to determine mRNA expression. RESULTS: An increase in the relative amount of RyR2 (111%) and SERCA mRNA (65 %) expression was observed in the hypertrophied rats (RyR2:77± 11; SERCA: 87± 10, n=9) compared with the normal rats (RyR2: 36± 10; SERCA: 53± 10, n=9). Propranolol was effective to inhibit the increase in RyR2 (51±7) and SERCA (63±13) mRNA expression in hypertrophied rats,respectively. Verapamil also reduced RyR2 (62±5) and SERCA (75±8) mRNA expression. CONCLUSION: Both RyR2 and SERCA mRNA level in L-thyroxin-induced cardiac hypertrophy was over-expressed and propranolol or verapamil inhibited the alteration.

  5. New test principle for measurement of free thyroxine (fT/sub 4/) in serum. Results of a multicenter trial

    Energy Technology Data Exchange (ETDEWEB)

    Mahlstedt, J.


    A new principle for measurement of free serum thyroxine was investigated being a nearly classical radioimmunoassay by use of an analogue of /sup 125/I-T/sub 4/, which does not bind to serum proteins but binds as well as T/sub 4/ to the T/sub 4/-antiserum. The distribution of 438 test-results of euthyroid patients with and without goitre is normal, anti x being 1.34 ng/dl with 2s-range between 0.73-1.95 ng/dl. This normal range was derived from areas in FRG known for more or less iodine deficiency. Thus fT/sub 4/ seems not to be strongly dependent on iodine intake. fT/sub 4/ in sera from pregnant women of the third trimester was clearly decreased, one half of the values being in the lower normal range, the other half being in the hypothyroid range. Patients on contraceptive therapy showed values within the normal range. Patients on T/sub 4/-supplementation in part revealed more or less increased values. Quality control was performed using 44 assays. The mean interassay variation coefficient was clearly less than 10% using three control sera in the euthyroid, hyperthyroid and extremely hypothyroid range. The technical handling of the assay is very convenient. The assay is to be performed within 2 hours.

  6. Beneficial role of ascorbic and folic acids antioxidants against thyroxin-induced testicular dysfunction in hyperthyroid rats. (United States)

    Beltagy, Doha M; Mohamed, Tarek M; El Said, Ahmed S; Tousson, Ehab


    Thyroid hormones play a fundamental role in the regulation of metabolism of almost all mammalian tissue including the reproductive system. Hyperthyroidism in early life may cause delayed sexual maturation, although physical development is normal and skeletal growth may be accelerated. Hyperthyroidism after puberty influences reproductive functions and increases testosterone level. The aim of this work is to study the effect of induced hyperthyroidism by L-thyroxine sodium administration on the testis of rats and to evaluate the ameliorating role of different antioxidants as ascorbic acid and folic acid on the hyperthyroid state via the assessment of different biochemical markers, histopathological and immunochemical sections. DNA analysis of the D1 deiodinase was performed to determine genetic mutation due to hyperthyroidism. The results showed partially disrupted in the measured biochemical parameters and spermatogenesis in hyperthyroid rats. Post-administration of both folic and ascorbic acids together in hyperthyroid rats showed the best ameliorating effects on the thyroid hormones, testosterone, testicular GGT and ALP, and all oxidative stress markers. There is no genetic mutations that occurred in D1 deiodinase due to hyperthyroidism. These findings were indicated by the proliferating cell nuclear antigen (PCNA) studies of testes.

  7. Evaluation of routine hematology profile results and fructosamine, thyroxine, insulin, and proinsulin concentrations in lean, overweight, obese, and diabetic cats. (United States)

    Hoenig, Margarethe; Traas, Anne M; Schaeffer, David J


    To compare results of hematologic testing in nondiabetic and diabetic cats to identify possible indicators of alterations in long-term glucose control. Cross-sectional study. 117 client-owned cats (76 nondiabetic cats [25 with normal body condition, 27 overweight, and 24 obese] and 41 naïve [n = 21] and treated [20] diabetic cats). Signalment and medical history, including data on feeding practices, were collected. A body condition score was assigned, and feline body mass index was calculated. Complete blood counts and serum biochemical analyses, including determination of fructosamine, thyroxine, insulin, and proinsulin concentrations, were performed. Urine samples were obtained and analyzed. Glucose and fructosamine concentrations were significantly higher in the naïve and treated diabetic cats than in the nondiabetic cats. Insulin and proinsulin concentrations were highest in the obese cats but had great individual variation. Few other variables were significantly different among cat groups. Most cats, even when obese or diabetic, had unlimited access to food. Results suggested that cats at risk of developing diabetes (ie, overweight and obese cats) could not be distinguished from cats with a normal body condition on the basis of results of isolated hematologic testing. A longitudinal study is indicated to follow nondiabetic cats over a period of several years to identify those that eventually develop diabetes. Findings also suggested that dietary education of cat owners might be inadequate.

  8. Conversion of L-thyroxine to L-triiodothyronine in the rat liver under in vitro conditions

    Energy Technology Data Exchange (ETDEWEB)

    Nauman, A.; Kaminski, T.; Pastuszko, D. (Centrum Medyczne Ksztalcenia Podyplomowego, Warsaw (Poland))


    Conversion of thyroxine (T/sub 4/) to triiodothyronine (T/sub 3/) has been studied in liver homogenates obtained from normal and hypothyroid rats. Liver homogenates were incubated for 0-60 minutes at 37/sup 0/C in Tris buffer containing sucrose and T/sub 4/, pH 7.4. T/sub 3/ generated during incubation was measured by a specific radioimmunoassay of an ethanol extract of the incubates. Conversion rate of T/sub 4/ to T/sub 3/ by liver homogenates from intact rats was found to be time, protein concentration and substrate concentration (T/sub 4/) dependent. Heating of homogenate above 60/sup 0/C abolished while cooling significantly decreased the monodeiodination. In homogenates from hypothyroid rats the conversion and its rate were significantly decreased. The results of present study confirmed enzymatic character of monodeiodination reaction. Decreased conversion of T/sub 4/ to T/sub 3/ in hypothyroidism suggests that biosynthesis of converting enzyme may be regulated by thyroid hormones.

  9. Apical Localization of Zinc Transporter ZnT4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Chiara Murgia


    Full Text Available The apical cytoplasm of airway epithelium (AE contains abundant labile zinc (Zn ions that are involved in the protection of AE from oxidants and inhaled noxious substances. A major question is how dietary Zn traffics to this compartment. In rat airways, in vivo selenite autometallographic (Se-AMG-electron microscopy revealed labile Zn-selenium nanocrystals in structures resembling secretory vesicles in the apical cytoplasm. This observation was consistent with the starry-sky Zinquin fluorescence staining of labile Zn ions confined to the same region. The vesicular Zn transporter ZnT4 was likewise prominent in both the apical and basal parts of the epithelium both in rodent and human AE, although the apical pools were more obvious. Expression of ZnT4 mRNA was unaffected by changes in the extracellular Zn concentration. However, levels increased 3-fold during growth of cells in air liquid interface cultures and decreased sharply in the presence of retinoic acid. When comparing nasal versus bronchial human AE cells, there were significant positive correlations between levels of ZnT4 from the same subject, suggesting that nasal brushings may allow monitoring of airway Zn transporter expression. Finally, there were marked losses of both basally-located ZnT4 protein and labile Zn in the bronchial epithelium of mice with allergic airway inflammation. This study is the first to describe co-localization of zinc vesicles with the specific zinc transporter ZnT4 in airway epithelium and loss of ZnT4 protein in inflamed airways. Direct evidence that ZnT4 regulates Zn levels in the epithelium still needs to be provided. We speculate that ZnT4 is an important regulator of zinc ion accumulation in secretory apical vesicles and that the loss of labile Zn and ZnT4 in airway inflammation contributes to AE vulnerability in diseases such as asthma.

  10. A High-Fidelity Codon Set for the T4 DNA Ligase-Catalyzed Polymerization of Modified Oligonucleotides. (United States)

    Lei, Yi; Kong, Dehui; Hili, Ryan


    In vitro selection of nucleic acid polymers can readily deliver highly specific receptors and catalysts for a variety of applications; however, it is suspected that the functional group deficit of nucleic acids has limited their potential with respect to proteinogenic polymers. This has stimulated research toward expanding their chemical diversity to bridge the functional gap between nucleic acids and proteins to develop a superior biopolymer. In this study, we investigate the effect of codon library size and composition on the sequence specificity of T4 DNA ligase in the DNA-templated polymerization of both unmodified and modified oligonucleotides. Using high-throughput DNA sequencing of duplex pairs, we have uncovered a 256-membered codon set that yields sequence-defined modified ssDNA polymers in high yield and with high fidelity.

  11. Genetic effects of cosmic radiation on bacteriophage T4Br/+/ /On materials of biological experiment Soyuz-Apollo/

    Energy Technology Data Exchange (ETDEWEB)

    Iurov, S.S. (Academy of Sciences, Institute of Biological Physics, Pushchino, USSR); Akoev, I.G. (Ministerstvo Zdravookhraneniia SSSR, Institut Mediko-Biologicheskikh Problem, Moscow, USSR)


    During the experiment Spore-ring Forming Fungi Biorhythm of the Apollo-Soyuz test project the Rhythm-1 apparatus contained a dried film culture of bacteriophage T4Br(+), growing cultures of Actinomyces and plastic nuclear particle detectors. The following were studied: the frequency of induction of r mutations in the bacteriophage film per 20,000 surviving particles, the spectrum of mutant types obtained (rI, rII, rIII), and the possible molecular mechanisms for the occurrence of rII mutants with due regard to the registered tracks of heavy nuclear particles. The studies showed that the local radiation due to heavy nuclear particle tracks plays a major role in space radiation damage.

  12. On the spectrum of AdS3 x S3 x T4 strings with Ramond-Ramond flux

    CERN Document Server

    Borsato, Riccardo; Sfondrini, Alessandro; Stefanski, Bogdan


    We analyze the spectrum of perturbative closed strings on AdS3 x S3 x T4 with Ramond-Ramond flux using integrable methods. By solving the crossing equations we determine the massless and mixed-mass dressing factors of the worldsheet S matrix and derive the Bethe equations. Using these, we construct the underlying integrable spin chain and show that it reproduces the reducible spin chain conjectured at weak coupling in arXiv:1211.1952. We find that the string-theory massless modes are described by gapless excitations of the spin chain. The resulting degeneracy of vacua matches precisely the protected supergravity spectrum found by de Boer.

  13. The Caulobacter crescentus transducing phage Cr30 is a unique member of the T4-like family of myophages. (United States)

    Ely, Bert; Gibbs, Whitney; Diez, Simon; Ash, Kurt


    Bacteriophage Cr30 has proven useful for the transduction of Caulobacter crescentus. Nucleotide sequencing of Cr30 DNA revealed that the Cr30 genome consists of 155,997 bp of DNA that codes for 287 proteins and five tRNAs. In contrast to the 67 % GC content of the host genome, the GC content of the Cr30 genome is only 38 %. This lower GC content causes both the codon usage pattern and the amino acid composition of the Cr30 proteins to be quite different from those of the host bacteria. As a consequence, the Cr30 mRNAs probably are translated at a rate that is slower than the normal rate for host mRNAs. A phylogenetic comparison of the genome indicates that Cr30 is a member of the T4-like family that is most closely related to a new group of T-like phages exemplified by фM12.

  14. T4 fibrations over Calabi–Yau two-folds and non-Kähler manifolds in string theory

    Directory of Open Access Journals (Sweden)

    Hai Lin


    Full Text Available We construct a geometric model of eight-dimensional manifolds and realize them in the context of type II string theory. These eight-manifolds are constructed by non-trivial T4 fibrations over Calabi–Yau two-folds. These give rise to eight-dimensional non-Kähler Hermitian manifolds with SU(4 structure. The eight-manifold is also a circle fibration over a seven-dimensional G2 manifold with skew torsion. The eight-manifolds of this type appear as internal manifolds with SU(4 structure in type IIB string theory with F3 and F7 fluxes. These manifolds have generalized calibrated cycles in the presence of fluxes.

  15. T4-related bacteriophage LIMEstone isolates for the control of soft rot on potato caused by 'Dickeya solani'.

    Directory of Open Access Journals (Sweden)

    Evelien M Adriaenssens

    Full Text Available The bacterium 'Dickeya solani', an aggressive biovar 3 variant of Dickeya dianthicola, causes rotting and blackleg in potato. To control this pathogen using bacteriophage therapy, we isolated and characterized two closely related and specific bacteriophages, vB_DsoM_LIMEstone1 and vB_DsoM_LIMEstone2. The LIMEstone phages have a T4-related genome organization and share DNA similarity with Salmonella phage ViI. Microbiological and molecular characterization of the phages deemed them suitable and promising for use in phage therapy. The phages reduced disease incidence and severity on potato tubers in laboratory assays. In addition, in a field trial of potato tubers, when infected with 'Dickeya solani', the experimental phage treatment resulted in a higher yield. These results form the basis for the development of a bacteriophage-based biocontrol of potato plants and tubers as an alternative for the use of antibiotics.

  16. Effects of Weaving Laser on Weld Microstructure and Crack for Al 6k21-T4 Alloy

    Institute of Scientific and Technical Information of China (English)

    B.H. Kim; N.Y. Kang; W.T. Oh; C.H. Kim; J.H. Kim; Y.S. Kim; Y.H. Park


    For Al 6k21-T4 overlap weld joint, the shear-tensile strength by using the weaving laser was improved as compared to the case of linear laser. For the specimen of low strength, the porosity was distributed continuously along the intersection between the plates and fusion line. However, for the optimized welding condition, large oval-shaped porosities were located only in the advancing track of the concave part. Therefore, the continuity of cracks and porosities played a key role to determine the strength. And, the weaving width was also the important parameter to control the strength. Furthermore, the concave part had more significant hot and cold cracking in the weld and heat-affected zone (HAZ), respectively, than the convex part.

  17. Evaluation of forming limit in viscous pressure forming of automotive aluminum alloy 6k21-T4 sheet

    Institute of Scientific and Technical Information of China (English)


    A ductile fracture criterion is introduced into numerical simulation to predict viscous pressure forming limit of the automotive body aluminum alloy 6k21-T4. The material constant in the ductile fracture criterion is determined by the combination of the viscous pressure bulging (VPB) test with numerical simulation. VPB tests of the aluminum alloy sheet are carried out by using various elliptical dies with different ratios of major axis to minor axis(β), and the bugling processes are simulated by the aid of the finite element method software LS-DYNA3D. On the basis of the stress and strain calculated from numerical simulations, the forming limits of bulging specimens obtained are predicted by the ductile fracture criterion, and compared with experimental results.The fracture initiation site and the minimal thickness predicted by the ductile fracture criterion are in good agreement with the experimental results.

  18. On the spectrum of AdS3 × S 3 × T 4 strings with Ramond-Ramond flux (United States)

    Borsato, Riccardo; Ohlsson Sax, Olof; Sfondrini, Alessandro; Stefański, Bogdan, Jr.


    We analyze the spectrum of perturbative closed strings on {{AdS}}3× {S}3× {T}4 with Ramond-Ramond flux using integrable methods. By solving the crossing equations we determine the massless and mixed-mass dressing factors of the worldsheet S matrix and derive the Bethe equations. Using these, we construct the underlying integrable spin chain and show that it reproduces the reducible spin chain conjectured at weak coupling in Olof Ohlsson S, Bogdan S Jr and Torrielli A 2013 (arXiv:1211.1952). We find that the string-theory massless modes are described by gapless excitations of the spin chain. The resulting degeneracy of vacua matches precisely the protected supergravity spectrum found by de Boer.

  19. Dioxin-like and perfluorinated compounds in pigs in an Indian open waste dumping site: toxicokinetics and effects on hepatic cytochrome P450 and blood plasma hormones. (United States)

    Watanabe, Michio X; Kunisue, Tatsuya; Tao, Lin; Kannan, Kurunthachalam; Subramanian, Annamalai; Tanabe, Shinsuke; Iwata, Hisato


    Dioxins and related compounds (DRCs) and perfluorinated compounds were measured in the livers of pigs (Sus scrofa) collected from an open waste dumping site in South India. Hepatic concentrations of DRCs and perfluorooctanesulfonate (PFOS; up to 200 ng/g wet wt) were significantly higher in male and female pigs, respectively, collected from the dumping site than in those from a reference site. Results suggest that dumping sites are a source of DRCs and PFOS. Hepatic concentrations of DRCs in piglets were higher than in mothers, especially for the congeners with molecular weights in the range of 360 to 400, implying congener-specific maternal transfer of DRCs in swine. Concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans and some non-ortho dioxin-like polychlorinated biphenyls (PCBs) in the liver of pigs were higher than those in the adipose fat and muscle of the same specimens. In addition, the liver-to-adipose concentration ratios for each congener had a significant positive correlation with the levels of hepatic cytochrome P450 (CYP)1A-like protein, suggesting congener-specific and CYP1A-dependent hepatic sequestration of DRCs in the swine. Total hepatic 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs; 8.9-350 pg/g fat wt) had a significant positive correlation with CYP1A-like protein expression (r=0.56, p=0.012), suggesting the induction of CYP1A by DRCs. However, the total TEQs had a significant negative correlation with CYP4A-like protein (r=-0.49, p=0.029), suggesting repression of peroxisome proliferator-activated receptor-alpha (PPARalpha)-mediated signaling pathway by DRCs. Decreases in plasma total thyroxine (T4), free T4, and immunoglobulin (Ig) G were also found in pigs from the dumping site compared with those from the reference site. This study provides insight into the toxicological impacts of DRCs and perfluorinated compounds in wild animals from open waste dumping sites.

  20. Genomic analysis of oceanic cyanobacterial myoviruses compared with T4-like myoviruses from diverse hosts and environments. (United States)

    Sullivan, Matthew B; Huang, Katherine H; Ignacio-Espinoza, Julio C; Berlin, Aaron M; Kelly, Libusha; Weigele, Peter R; DeFrancesco, Alicia S; Kern, Suzanne E; Thompson, Luke R; Young, Sarah; Yandava, Chandri; Fu, Ross; Krastins, Bryan; Chase, Michael; Sarracino, David; Osburne, Marcia S; Henn, Matthew R; Chisholm, Sallie W


    T4-like myoviruses are ubiquitous, and their genes are among the most abundant documented in ocean systems. Here we compare 26 T4-like genomes, including 10 from non-cyanobacterial myoviruses, and 16 from marine cyanobacterial myoviruses (cyanophages) isolated on diverse Prochlorococcus or Synechococcus hosts. A core genome of 38 virion construction and DNA replication genes was observed in all 26 genomes, with 32 and 25 additional genes shared among the non-cyanophage and cyanophage subsets, respectively. These hierarchical cores are highly syntenic across the genomes, and sampled to saturation. The 25 cyanophage core genes include six previously described genes with putative functions (psbA, mazG, phoH, hsp20, hli03, cobS), a hypothetical protein with a potential phytanoyl-CoA dioxygenase domain, two virion structural genes, and 16 hypothetical genes. Beyond previously described cyanophage-encoded photosynthesis and phosphate stress genes, we observed core genes that may play a role in nitrogen metabolism during infection through modulation of 2-oxoglutarate. Patterns among non-core genes that may drive niche diversification revealed that phosphorus-related gene content reflects source waters rather than host strain used for isolation, and that carbon metabolism genes appear associated with putative mobile elements. As well, phages isolated on Synechococcus had higher genome-wide %G+C and often contained different gene subsets (e.g. petE, zwf, gnd, prnA, cpeT) than those isolated on Prochlorococcus. However, no clear diagnostic genes emerged to distinguish these phage groups, suggesting blurred boundaries possibly due to cross-infection. Finally, genome-wide comparisons of both diverse and closely related, co-isolated genomes provide a locus-to-locus variability metric that will prove valuable for interpreting metagenomic data sets.

  1. Histopathological predictors for local recurrence in patients with T3 and T4 rectal cancers without preoperative chemoradiotherapy. (United States)

    Akagi, Yoshito; Hisaka, Toru; Mizobe, Tomoaki; Kinugasa, Tetsushi; Ogata, Yutaka; Shirouzu, Kazuo


    Identification of suitable predictors of local recurrence (LR) in patients with rectal cancer would be of clinical benefit. The aim of this study was to identify histopathological factors that could predict LR. A total of 796 stage II/III patients with pT3 and pT4 rectal cancer who did not undergo preoperative chemoradiation were enrolled. LR was defined as intra-pelvic recurrence only. Histopathological factors related to LR were investigated. LR was found in 25 patients (6.1%) with stage II and 54 patients (13.9%) with stage IIIB/IIIC. In patients with stage II, distance of mesorectal extension (DME) >4 mm (P = 0.011) and positive venous invasion (P = 0.035) were independent factors that predicted LR. In patients with stage IIIB/IIIC, circumferential resection margin (CRM) ≤1 mm (P = 0.003) and positive lymphatic invasion (P = 0.006) were independent factors. The cumulative 5-year LR rate was higher (11.9%) in patients with a combination of DME > 4 mm and/or positive venous invasion for stage II (P CRM≤1 mm and/or positive lymphatic invasion for stage IIIB and IIIC (22.2%; P < 0.002, and 34.3%; P < 0.006, respectively). Important histopathological predictors for LR in patients with pT3 and pT4 rectal cancer were different at each stage. © 2014 Wiley Periodicals, Inc.

  2. Partial deficiency of thyroxine-binding globulin-Allentown is due to a mutation in the signal peptide. (United States)

    Fingerhut, Anja; Reutrakul, Sirimon; Knuedeler, Sebastian D; Moeller, Lars C; Greenlee, Carol; Refetoff, Samuel; Janssen, Onno E


    We present an unusual variant of T(4)-binding globulin (TBG) found in a family from Allentown, Pennsylvania (TBG-AT). The heterozygous proposita presented serum total T(4) and TBG levels ranging from low to normal. TBG gene sequencing revealed a C-to-T substitution in codon -2 (CAC to TAC) leading to the substitution of the normal histidine by a tyrosine within the signal peptide. No mutation within the mature peptide was found. Allele-specific PCR confirmed the H(-2)Y mutation in the propositas mother and son. T(4)-binding analysis of TBG in serum from the proposita and son showed normal affinity but reduced capacity when compared with the unaffected father. Heat stability and isoelectric focusing of TBG-AT were normal. In vitro expression of a recombinant TBG-AT in Xenopus oocytes revealed a diminished secretory efficiency and confirmed the normal binding affinity and heat stability of the small amount of secreted TBG-AT. This study has defined impaired cotranslational processing as a hitherto unrecognized cause of hereditary TBG deficiency.

  3. Friction stir welding process of 6061-T4 aluminum alloy T-joints%6061-T4铝合金T型接头搅拌摩擦焊工艺

    Institute of Scientific and Technical Information of China (English)

    侯晓鹏; 杨新岐; 崔雷; 周光


    采用搅拌摩擦焊方法成功获得3种不同组合形式(搭接/对搭接/对接)的6061-T4铝合金T型接头。对接头的焊接缺陷、微观组织、硬度分布及抗拉强度分别进行观察和测试。结果表明:在前进侧圆角过渡区或筋板焊核区,3种接头均容易出现隧道缺陷;弱结合缺陷由于塑性变形偏离原始连接界面而向筋板或者壁板前进侧偏移;与常规搅拌摩擦焊对接搭接接头不同,T型接头沿筋板方向出现热机影响区和两个圆角过渡区;软化区域和弱结合是导致沿壁板拉伸强度降低的主要原因,而弱结合和隧道缺陷是引起这3种T型接头沿筋板方向断裂的重要原因。%Three combination modes (T-lap/T-butt-lap/T-butt) of AA6061-T4 aluminum alloy T-joints were successfully jointed by friction stir welding. Welding defects, microstructure, hardness profiles and tensile strength of the obtained T-joints were observed and measured, respectively. The results show that tunnel defects are easily formed in the fillet zone of the advancing side or in stringer nugget zone for all the three modes of T-joints. Defects of kissing bond are extruded downward to the stringer or sideward from the original joining surfaces to the advancing side of the skin under severe plastic deformation. T-joints exhibit the thermo-mechanical affected zone and two fillet zones in the stringer, which are different from the conventional butt and lap joints of friction stir welding. Softening zones and kissing bond are the main reasons to reduce the tensile strength of T-joints along skin direction, and kissing bond and tunnel defects are the main reasons for the fractures of T-joints along stringer direction.

  4. Structural characteristics and plant-beneficial effects of bacteria colonizing the shoots of field grown conventional and genetically modified T4-lysozyme producing potatoes

    NARCIS (Netherlands)

    Rasche, F.; Marco-Noales, E.; Velvis, H.; Overbeek, van L.S.; Lopez, M.M.; Elsas, van J.D.; Sessitsch, A.


    Genetically modified potatoes expressing antibacterial protein T4 lysozyme may offer effective control strategies for bacterial pathogens causing severe potato diseases. Apart from this beneficial effect, it is very important to investigate such engineered potatoes carefully for potential adverse ef

  5. Structural characteristics and plant-beneficial effects of bacteria colonizing the shoots of field grown conventional and genetically modified T4-lysozyme producing potatoes

    NARCIS (Netherlands)

    Rasche, Frank; Marco-Noales, Ester; Velvis, Henk; van Overbeek, Leo S.; Lopez, Maria M.; van Elsas, Jan D.; Sessitsch, Angela


    Genetically modified potatoes expressing antibacterial protein T4 lysozyme may offer effective control strategies for bacterial pathogens causing severe potato diseases. Apart from this beneficial effect, it is very important to investigate such engineered potatoes carefully for potential adverse ef

  6. Identification of pre- and post-treatment markers, clinical, and laboratory parameters associated with outcome in renal cancer patients treated with MVA-5T4

    Directory of Open Access Journals (Sweden)

    Robert eAmato


    Full Text Available The recent approvals of immunotherapeutic agents (Sipuleucel-T and Ipilimumab for the treatment of different solid tumors gave a boost to the growing cancer immunotherapy field, even though few immunotherapy studies have demonstrated convincingly that there is a direct link between the predicted mode of action of an immunological compound and therapeutic benefit. MVA-5T4 (Trovax® is a novel vaccine combining the tumor-associated antigen 5T4 to an engineered vector-modified vaccinia Ankara (MVA. MVA helps to express the oncofetal 5T4 antigen and subsequently trigger a tumor-directed immune reaction. The safety and clinical benefit reported in multiple phase I and II clinical trials using MVA-5T4 were encouraging; immune responses were induced in almost all treated patients, and associations between 5T4-specific cellular or humoral responses and clinical benefit were reported in most of the nine phase II trials. In particular, clinical studies conducted in renal cell carcinoma (RCC patients have demonstrated an association between 5T4-specific (but not MVA antibody responses and enhanced survival. This review describes the clinical studies using MVA-5T4 conducted in RCC that convincingly demonstrated that an antigen-specific immune response induced by vaccination is associated with enhanced patient survival and is not simply a function of the general health of patients. We will also provide our expert opinions on possible future better-designed clinical trials based on relevant biomarkers. In addition, various combinations of MVA-5T4 and different and newer immunomodulator agents with promising clinical benefit will be discussed.

  7. In vivo effects of monoclonal anti-L3T4 antibody on immune responsiveness of mice infected with Schistosoma mansoni. Reduction of irradiated cercariae-induced resistance

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, E.A.; Colley, D.G.


    Mice can be partially protected against challenge infections of Schistosoma mansoni cercariae by either single or multiple exposure to irradiated cercariae (x-cerc). The participation of L3T4+ lymphocytes on this resistance phenomenon was evaluated by selectively depleting this cell population through in vivo administration of mAb anti-L3T4 at three different times in relationship to the challenge infections. Treatment with anti-L3T4 before challenge such that depletion was effective during the time of cercarial skin penetration and dermal/s.c. residence significantly reduced the level of resistance induced by x-cerc sensitization. When treatment was delayed until after challenge, depletion of L3T4+ cells coincided with either the lung or post-lung/liver phases of schistosomular migration, and normal levels of x-cerc-induced resistance were induced. In contrast to once-immunized mice, mice hyperimmunized by five exposures to x-cerc and then depleted of L3T4+ cells at the time of challenge still expressed resistance to the challenge. These data suggest that when mice are sensitized only once with x-cerc the challenge infection provides a necessary immunologic boost which requires L3T4+ cells for effective expression of resistance. The requirement for this anamnestic effect by the challenge infection can be circumvented by hyperimmunization. Evaluation of the immune response of one-time sensitized or hyperimmunized mice demonstrated that cellular Ag-specific proliferative responses and mitogen-induced lymphokine production were abrogated after any of the various in vivo regimens of anti-L3T4 antibody. In contrast, immunoblot analysis of humoral responsiveness revealed a correlation between the expression of resistance and the ability of sera from immunized and anti-L3T4 treated mice to recognize a 75-kDa parasite antigenic component.

  8. Activity Analysis of T4 DNA Ligase Based on Linear Fluorescence Probes%基于线性荧光探针对T4 DNA连接酶的活性分析

    Institute of Scientific and Technical Information of China (English)

    刘斌; 羊小海; 王柯敏; 谭蔚泓


    利用线性荧光探针作为核酸连接反应的模板和信号分子,通过实时监测荧光信号的降低来表征连接产物的生成过程,从而建立了一种连续、简单且特异性高的T4 DNA连接酶活性分析的新方法,检出限可达1.2 U/mL;同时,该方法还可用于快速考察金属离子和化学药物对酶促反应的影响.实验结果表明,该法不仅为灵敏、实时监测核酸连接反应提供了一种简便快捷的非同位素分析方法,也为开展核酸连接酶活性分析、反应动力学机制探讨和药物快速筛选提供了一种新技术.

  9. ModA and ModB, two ADP-ribosyltransferases encoded by bacteriophage T4: catalytic properties and mutation analysis. (United States)

    Tiemann, Bernd; Depping, Reinhard; Gineikiene, Egle; Kaliniene, Laura; Nivinskas, Rimas; Rüger, Wolfgang


    Bacteriophage T4 encodes three ADP-ribosyltransferases, Alt, ModA, and ModB. These enzymes participate in the regulation of the T4 replication cycle by ADP-ribosylating a defined set of host proteins. In order to obtain a better understanding of the phage-host interactions and their consequences for regulating the T4 replication cycle, we studied cloning, overexpression, and characterization of purified ModA and ModB enzymes. Site-directed mutagenesis confirmed that amino acids, as deduced from secondary structure alignments, are indeed decisive for the activity of the enzymes, implying that the transfer reaction follows the Sn1-type reaction scheme proposed for this class of enzymes. In vitro transcription assays performed with Alt- and ModA-modified RNA polymerases demonstrated that the Alt-ribosylated polymerase enhances transcription from T4 early promoters on a T4 DNA template, whereas the transcriptional activity of ModA-modified polymerase, without the participation of T4-encoded auxiliary proteins for middle mode or late transcription, is reduced. The results presented here support the conclusion that ADP-ribosylation of RNA polymerase and of other host proteins allows initial phage-directed mRNA synthesis reactions to escape from host control. In contrast, subsequent modification of the other cellular target proteins limits transcription from phage early genes and participates in redirecting transcription to phage middle and late genes.

  10. Structure-Function Analysis of the 3' Phosphatase Component of T4 Polynucleotide Kinase/phosphatase

    Energy Technology Data Exchange (ETDEWEB)

    Zhu,H.; Smith, P.; Wang, L.; Shuman, S.


    T4 polynucleotide kinase/phosphatase (Pnkp) exemplifies a family of bifunctional enzymes with 5'-kinase and 3' phosphatase activities that function in nucleic acid repair. T4 Pnkp is a homotetramer of a 301-aa polypeptide, which consists of an N-terminal kinase domain of the P-loop phosphotransferase superfamily and a C-terminal phosphatase domain of the DxD acylphosphatase superfamily. The homotetramer is formed via pairs of phosphatase-phosphatase and kinase-kinase homodimer interfaces. Here we identify four side chains-Asp187, Ser211, Lys258, and Asp277-that are required for 3' phosphatase activity. Alanine mutations at these positions abolished phosphatase activity without affecting kinase function or tetramerization. Conservative substitutions of asparagine or glutamate for Asp187 did not revive the 3' phosphatase, nor did arginine or glutamine substitutions for Lys258. Threonine in lieu of Ser211 and glutamate in lieu of Asp277 restored full activity, whereas asparagine at position 277 had no salutary effect. We report a 3.0 A crystal structure of the Pnkp tetramer, in which a sulfate ion is coordinated between Arg246 and Arg279 in a position that we propose mimics one of the penultimate phosphodiesters (5'NpNpNp-3') of the polynucleotide 3'-PO(4) substrate. The amalgam of mutational and structural data engenders a plausible catalytic mechanism for the phosphatase that includes covalent catalysis (via Asp165), general acid-base catalysis (via Asp167), metal coordination (by Asp165, Asp277 and Asp278), and transition state stabilization (via Lys258, Ser211, backbone amides, and the divalent cation). Other critical side chains play architectural roles (Arg176, Asp187, Arg213, Asp254). To probe the role of oligomerization in phosphatase function, we introduced six double-alanine cluster mutations at the phosphatase-phosphatase domain interface, two of which (R297A-Q295A and E292A-D300A) converted Pnkp from a tetramer to a dimer

  11. Effects of thyroxine on cardiac function and lymphocyte β-adrenoceptors in patients with chronic congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    卢新政; 黄峻; 张晓文; 李新华; 王赤京; 张佩生; 陈永生


    Objective To explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte β-adrenoceptors (β-Ars) of patients with chronic congestive heart failure (CHF). Methods Twenty-eight patients with class Ⅲ or Ⅳ advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM) were randomly divided into groups A and B. L-thyroxine (L-T50) was administered to group B. Exercise tolerance, chest X-rays, and echocardiographic parameters were obtained before and after one month of treatment, Ficoll-hypaque solution was used to separate peripheral lymphocytes, and 125I-pindolol radioligand binding was used to measure β-AR levels in peripheral lymphocytes. Results L-T50 therapy improved cardiac output [CO, (2.98±0.31)L/min vs (3.24±0.28) L/min, P<0.01], left ventricular ejection fraction (LVEF, 26.21%±3.21% vs 37.93%±9.01%, P<0.01), and decreased isovolumetric relaxation time (IVRT, 0.12±0.04 vs 0.10±0.02, P<0.01). Serum TH levels and the maximal number of β-AR binding sites (βmax ) in peripheral lymphocytes were lower in patients with CHF than in normal healthy people, but L-T50 administration induced a β-AR up-regulation on peripheral lymphocyte surfaces. L-T50 was well tolerated without episodes of ischemia or arrhythmia. There was no significant change in heart rate or metabolic rate.Conclusion TH administration improves cardiac function and β-AR expression in peripheral lymphocytes of patients with CHF.

  12. Brucella Rough Mutant Induce Macrophage Death via Activating IRE1α Pathway of Endoplasmic Reticulum Stress by Enhanced T4SS Secretion

    Directory of Open Access Journals (Sweden)

    Peng Li


    Full Text Available Brucella is a Gram-negative facultative intracellular pathogen that causes the worldwide zoonosis, known as brucellosis. Brucella virulence relies mostly on its ability to invade and replicate within phagocytic cells. The type IV secretion system (T4SS and lipopolysaccharide are two major Brucella virulence factors. Brucella rough mutants reportedly induce the death of infected macrophages, which is T4SS dependent. However, the underlying molecular mechanism remains unclear. In this study, the T4SS secretion capacities of Brucella rough mutant and its smooth wild-type strain were comparatively investigated, by constructing the firefly luciferase fused T4SS effector, BPE123 and VceC. In addition, quantitative real-time PCR and western blotting were used to analyze the T4SS expression. The results showed that T4SS expression and secretion were enhanced significantly in the Brucella rough mutant. We also found that the activity of the T4SS virB operon promoter was notably increased in the Brucella rough mutant, which depends on quorum sensing-related regulators of VjbR upregulation. Cell infection and cell death assays revealed that deletion of vjbR in the Brucella rough mutant absolutely abolished cytotoxicity within macrophages by downregulating T4SS expression. This suggests that up-regulation of T4SS promoted by VjbR in rough mutant ΔrfbE contribute to macrophage death. In addition, we found that the Brucella rough mutant induce macrophage death via activating IRE1α pathway of endoplasmic reticulum stress. Taken together, our study provide evidence that in comparison to the Brucella smooth wild-type strain, VjbR upregulation in the Brucella rough mutant increases transcription of the virB operon, resulting in overexpression of the T4SS gene, accompanied by the over-secretion of effecter proteins, thereby causing the death of infected macrophages via activating IRE1α pathway of endoplasmic reticulum stress, suggesting novel insights into the

  13. Structure and function of the small terminase component of the DNA packaging machine in T4-like bacteriophages

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Siyang; Gao, Song; Kondabagil, Kiran; Xiang, Ye; Rossmann, Michael G.; Rao, Venigalla B. (CUA); (Purdue)


    Tailed DNA bacteriophages assemble empty procapsids that are subsequently filled with the viral genome by means of a DNA packaging machine situated at a special fivefold vertex. The packaging machine consists of a 'small terminase' and a 'large terminase' component. One of the functions of the small terminase is to initiate packaging of the viral genome, whereas the large terminase is responsible for the ATP-powered translocation of DNA. The small terminase subunit has three domains, an N-terminal DNA-binding domain, a central oligomerization domain, and a C-terminal domain for interacting with the large terminase. Here we report structures of the central domain in two different oligomerization states for a small terminase from the T4 family of phages. In addition, we report biochemical studies that establish the function for each of the small terminase domains. On the basis of the structural and biochemical information, we propose a model for DNA packaging initiation.

  14. Residual Stress and Fatigue Strength of Hybrid Laser-MIG-Welded A7N01P-T4 (United States)

    Wang, Qiuying; Chen, Hui; Qiu, Peixian; Zhu, Zongtao


    A7N01P-T4 aluminum alloy is widely used in some important welded components of high-speed trains. The hybrid laser-metal inert gas (MIG) welding process was studied to solve problems associated with the MIG welding process, such as low welding efficiency, high residual stress and deformation, and serious loss of strength. A high-speed camera, a voltage and current collection system, and NI DAQ were used to acquire arc profiles, welding voltage, and welding current simultaneously. Thermal cycle tests were carried out. Residual stresses induced by the welding process and fatigue strength of the joint were investigated. Large-size fatigue specimens were used in fatigue tests. The results show that the energy of the hybrid welding process is focused, and the power density of hybrid welding process is intense. The heat input per unit of the hybrid welding process is only half of that of the MIG welding process. Compared with the MIG welded joint, the overall residual stress level of the hybrid-welded joint is lower. The peak longitudinal stress of the hybrid-welded joint is reduced by 20 pct. The fatigue strength of hybrid joints is 14 pct higher than that of MIG-welded joints. Narrow weld and HAZ, weak softening behavior, and low residual stress level are the causes of the improvement of fatigue strength.

  15. Acanthamoeba belonging to T3, T4, and T11: genotypes isolated from air-conditioning units in Santiago, Chile. (United States)

    Astorga, Berbeli; Lorenzo-Morales, Jacob; Martín-Navarro, Carmen M; Alarcón, Verónica; Moreno, Johanna; González, Ana C; Navarrete, Elizabeth; Piñero, José E; Valladares, Basilio


    Free-living amoebae (FLA) of the genus Acanthamoeba are widely distributed in the environment, in the air, soil, and water, and have also been isolated from air-conditioning units. The objective of this work was to investigate the presence of this genus of FLA in the air-conditioning equipment at the Institute of Public Health of Chile in Santiago, Chile. Water and air samples were collected from air-conditioning systems and were checked for the presence of Acanthamoeba spp. Positive samples were further classified at the genotype level after sequencing the highly variable diagnostic fragment 3 (DF3) region of the 18S rRNA gene. This is the first report of the T3, T4, and T11 genotypes of Acanthamoeba in air-conditioning units from Chile. Overall, the widespread distribution of potentially pathogenic Acanthamoeba strains in the studied source demands more awareness within the public and health professionals in Chile as this pathogen is emerging as a risk for human health worldwide. © 2011 The Author(s) Journal of Eukaryotic Microbiology © 2011 International Society of Protistologists.

  16. Crystal Structure of the Carboxy-Terminal Region of the Bacteriophage T4 Proximal Long Tail Fiber Protein Gp34

    Directory of Open Access Journals (Sweden)

    Meritxell Granell


    Full Text Available Long tail fibers of bacteriophage T4 are formed by proteins gp34, gp35, gp36, and gp37, with gp34 located at the phage-proximal end and gp37 at the phage-distal, receptor-binding end. We have solved the structure of the carboxy-terminal region of gp34, consisting of amino acids 894–1289, by single-wavelength anomalous diffraction and extended the structure to amino acids 744–1289 using data collected from crystals containing longer gp34-fragments. The structure reveals three repeats of a mixed α-β fibrous domain in residues 744 to 877. A triple-helical neck connects to an extended triple β-helix domain (amino acids 900–1127 punctuated by two β-prism domains. Next, a β-prism domain decorated with short helices and extended β-helices is present (residues 1146–1238, while the C-terminal end is capped with another short β-helical region and three β-hairpins. The structure provides insight into the stability of the fibrous gp34 protein.

  17. Statistical Evaluation of Trace Metals, TSH and T4 in Blood Serum of Thyroid Disease Patients in Comparison with Controls. (United States)

    Hanif, Sidra; Ilyas, Asim; Shah, Munir H


    The present study is based on the measurement of concentrations of selected trace metals (Fe, Zn, Cu, Co, Mn, Ni, Cr, Cd and Pb) and thyroid hormones (TSH and T4) in blood serum of hypothyroid and hyperthyroid patients in comparison with healthy donors/controls in order to establish the imbalances of the trace metals in diseased subjects. The serum samples were digested in HNO3-HClO4 mixture and quantification of the metals was performed by flame atomic absorption spectrometry. Average levels of Fe, Ni, Cu, Cr, Pb and TSH were found to be significantly higher (p trace metals in the serum of patient groups revealed significantly different mutual associations compared with the controls. PCA and CA pointed out the interferences of the toxic metals with essential metals in the serum of both patient groups compared with the controls. Most of the metals exhibited noticeable disparities in their concentrations based on gender, food habits and tobacco use for all donor groups. Thus, the pathogenesis of thyroid diseases is significantly affecting the essential trace and toxic metals balance in both patients groups.

  18. Residual Stress and Fatigue Strength of Hybrid Laser-MIG-Welded A7N01P-T4 (United States)

    Wang, Qiuying; Chen, Hui; Qiu, Peixian; Zhu, Zongtao


    A7N01P-T4 aluminum alloy is widely used in some important welded components of high-speed trains. The hybrid laser-metal inert gas (MIG) welding process was studied to solve problems associated with the MIG welding process, such as low welding efficiency, high residual stress and deformation, and serious loss of strength. A high-speed camera, a voltage and current collection system, and NI DAQ were used to acquire arc profiles, welding voltage, and welding current simultaneously. Thermal cycle tests were carried out. Residual stresses induced by the welding process and fatigue strength of the joint were investigated. Large-size fatigue specimens were used in fatigue tests. The results show that the energy of the hybrid welding process is focused, and the power density of hybrid welding process is intense. The heat input per unit of the hybrid welding process is only half of that of the MIG welding process. Compared with the MIG welded joint, the overall residual stress level of the hybrid-welded joint is lower. The peak longitudinal stress of the hybrid-welded joint is reduced by 20 pct. The fatigue strength of hybrid joints is 14 pct higher than that of MIG-welded joints. Narrow weld and HAZ, weak softening behavior, and low residual stress level are the causes of the improvement of fatigue strength.

  19. Effect of Travel Speed on the Stress Corrosion Behavior of Friction Stir Welded 2024-T4 Aluminum Alloy (United States)

    Wang, Wen; Li, Tianqi; Wang, Kuaishe; Cai, Jun; Qiao, Ke


    The effect of travel speed on stress corrosion cracking (SCC) behavior of friction stir welded 2024-T4 aluminum alloy was investigated by slow strain rate tensile test. Microstructure and microhardness of the welded joint were studied. The results showed that the size of second phase particles increased with increasing travel speed, and the distribution of second phase particles was much more homogeneous at lower travel speed. The minimum microhardness was located at the boundary of nugget zone and thermomechanically affected zone. In addition, the SCC susceptibility of the friction stir welded joint increased with the increase of travel speed, owing to the size and distribution of second phase particles in the welds. The anodic applied potentials of -700, -650, -600 mV, and cathodic applied potential of -1200 mV facilitated SCC while the cathodic applied potential of -1000 mV improved the SCC resistance. The SCC behavior was mainly controlled by the metal anodic dissolution at the open circuit potential, and hydrogen accelerated metal embrittlement.

  20. Microstructural Characteristics and Mechanical Properties of Friction Stir Spot Welded 2A12-T4 Aluminum Alloy

    Directory of Open Access Journals (Sweden)

    Huijie Liu


    Full Text Available 2A12-T4 aluminum alloy was friction stir spot welded, and the microstructural characteristics and mechanical properties of the joints were investigated. A softened microstructural region existed in the joint, and it consisted of stir zone (SZ, thermal mechanically affected zone (TMAZ, and heat affected zone (HAZ. The minimum hardness was located in TMAZ, and the average hardness value in SZ can be improved by appropriately increasing welding heat input. The area of complete bonding region at the interface increased with increasing welding heat input because more interface metals were mixed. In a certain range of FSSW parameters, the tensile shear failure load of the joint increased with increasing rotation speed, but it decreased with increasing plunge rate or decreasing shoulder plunging depth. Two kinds of failure modes, that is, shear fracture mode and tensile-shear mixed fracture mode, can be observed in the tensile shear tests, and the joint that failed in the tensile-shear mixed fracture mode possessed a high carrying capability.

  1. Molecular characterization of the t(4;12)(q27~28;q14~15) chromosomal rearrangement in lipoma. (United States)

    Agostini, Antonio; Gorunova, Ludmila; Bjerkehagen, Bodil; Lobmaier, Ingvild; Heim, Sverre; Panagopoulos, Ioannis


    Lipomas are common benign soft tissue tumors whose genetic and cytogenetic features are well characterized. The karyotype is usually near- or pseudodiploid with characteristic structural chromosomal aberrations. The most common rearrangements target the high mobility group AT-hook 2 (HMGA2) gene in 12q14.3, with breakpoints occurring within or outside of the gene locus leading to deregulation of HMGA2. The most common fusion partner for HMGA2 in lipoma is lipoma-preferred partner (3q27), but also other genes frequently recombine with HMGA2. Furthermore, truncated HMGA2 transcripts are recurrently observed in lipomas. The present study describes 5 lipomas carrying the translocation t(4;12)(q27~28;q14~15) as the sole chromosomal anomaly, as well as 1 lipoma in which the three-way translocation t(1;4;12)(q21;q27~28;q14~15) was identified. Molecular analyses performed on 4 of these cases detected 4 truncated forms of HMGA2. In 3 tumors, the HMGA2 truncated transcripts included sequences originating from the chromosomal sub-band 4q28.1. Notably, in 2 of these cases, the fourth exon of HMGA2 was fused to transposable elements located in 4q28.1.

  2. Overexpression, purification, and partial characterization of ADP-ribosyltransferases modA and modB of bacteriophage T4. (United States)

    Tiemann, B; Depping, R; Rüger, W


    There is increasing experimental evidence that ADP-ribosylation of host proteins is an important means to regulate gene expression of bacteriophage T4. Surprisingly, this phage codes for three different ADP-ribosyltransferases, gene products Alt, ModA, and ModB, modifying partially overlapping sets of host proteins. While gene product Alt already has been isolated as a recombinant protein and its action on host RNA polymerases and transcription regulation have been studied, the nucleotide sequences of the two mod genes was published only recently. Their mode of action in the course of the infection cycle and the consequences of the ADP-ribosylations catalyzed by these enzymes remain to be investigated. Here we describe the cloning of the genes, the overexpression, purification, and partial characterization of ADP-ribosyltransferases ModA and ModB. Both proteins seem to act independently, and the ADP-ribosyl moieties are transferred to different sets of host proteins. While gene product ModA, similarly to the Alt protein, acts also on the alpha-subunit of host RNA polymerase, the ModB activity serves another set of proteins, one of which was identified as the S1 protein associated with the 30S subunit of the E. coli ribosomes.

  3. Effective inhibition of lytic development of bacteriophages λ, P1 and T4 by starvation of their host, Escherichia coli

    Directory of Open Access Journals (Sweden)

    Węgrzyn Alicja


    Full Text Available Abstract Background Bacteriophage infections of bacterial cultures cause serious problems in genetic engineering and biotechnology. They are dangerous not only because of direct effects on the currently infected cultures, i.e. their devastation, but also due to a high probability of spreading the phage progeny throughout a whole laboratory or plant, which causes a real danger for further cultivations. Therefore, a simple method for quick inhibition of phage development after detection of bacterial culture infection should be very useful. Results Here, we demonstrate that depletion of a carbon source from the culture medium, which provokes starvation of bacterial cells, results in rapid inhibition of lytic development of three Escherichia coli phages, λ, P1 and T4. Since the effect was similar for three different phages, it seems that it may be a general phenomenon. Moreover, similar effects were observed in flask cultures and in chemostats. Conclusion Bacteriophage lytic development can be inhibited efficiently by carbon source limitation in bacterial cultures. Thus, if bacteriophage contamination is detected, starvation procedures may be recommended to alleviate deleterious effects of phage infection on the culture. We believe that this strategy, in combination with the use of automated and sensitive bacteriophage biosensors, may be employed in the fermentation laboratory practice to control phage outbreaks in bioprocesses more effectively.

  4. The Thyroid Axis and Brain 5’-Monodeiodination of Thyroxine in the Burned Rat Model of Nonthyroidal Illness (United States)


    THYROID - 0 1..1 ECTOMY ( SHAM13URN 1’•4 i𔃻 14__ DAYS DAY fig. 1. Thyroid axis hormones and brain T4-to-T3 deiodination index (DI) at the indicated time...ABSTRACT""-’ Rats with a cutaneous burn exhibited a burn-size-related . depression of sertim thyroid hormones 2 weeks after Lnjury. Thyroidectomized rats... thyroid hormones were S not seen in burned rats. The depression of serum thyronines and thyrotrophin suggests that the burned rat may be a model for

  5. 精神分裂症患者攻击行为与血清甲状腺素睾酮水平的相关性%Correlation between aggressive behavior and serum thyroxine or testosterone level in schizophrenic

    Institute of Scientific and Technical Information of China (English)

    王小全; 马素杰; 张永录; 周海晓; 丁志杰


    schizophrenics were assessed with the Brief Psychiatric Rating Scale (BPRS) and aggressive behaviors with past violence history and Modified O‐vert Aggression Scale (MOAS) ,70 patients with aggressive behaviors assigned to research group ,and 50 ones without to control group .Thyroid stimulating hormone (TSH) ,serum free triiodothyronine (FT3) , serum free thyroxine (FT4) ,total triiodothyronine (T T3) ,total thyroxine (T T4) and testosterone (Tes‐to) levels were detected .Contrastive and correlation analyses of detection results were conducted .Results TT3 and FT3 levels were significantly higher (P<0 .05) and TSH lower (P<0 .01) in research than in control group .TT3 levels were positively related to verb aggression and aggression against property score of the MOAS (P<0 .05) and negatively to lack of vitality of the BPRS (P<0 .05);FT3 levels were posi‐tively related to aggression against property and self‐aggression (P<0 .05);male serum Testo levels were positively related to verb aggression and self‐aggression (P<0 .05) and negatively to lack of vitality (P<0 .05);female serum Testo levels were positively related to self‐aggression (P<0 .05) and negatively to lack of vitality (P< 0 .05);Conclusion Aggressi