The use of cyclophosphamide as an enhancer of the vaccine against foot-and-mouth disease

The immunization of biungulate animals with killed foot-and-mouth disease virus (FMDV) requires periodic vaccinations due to a low vaccine immunogenicity. Therefore, FMDV antigens need to be combined with adjuvants such as aluminum hydroxide, saponin or oil emulsions. Animal handling for periodic inoculations, and the repeated doses of vaccines that have to be administered increase the commercialization costs. Moreover, the use of adjuvants may induce adverse effects.In the present work we show that it is possible to increase the life span of neutralizing antibodies in serum when a single dose of cyclophosphamide (Cy) is administered four days before vaccination with aluminum hydroxidesaponin FMDV vaccine.     

Release of 3,5,3'-triiodothyronine, thyroxine and thyroglobulin from TSH-stimulated mouse thyroids in the perifusion system

We established a perifusion system using mouse thyroid glands. In this system, TSH increased the release of T3 and T4 significantly, and the response of thyroglobulin to TSH was delayed in comparison with that of T3 and T4.     

Release of 3,5,3′-triiodothyronine,thyroxine and thyroglobulin from TSH-stimulated mouse thyroids in the perifusion system

Summary We established a perifusion system using mouse thyroid glands. In this system, TSH increased the release of T₃ and T₄ significantly, and the response of thyroglobulin to TSH was delayed in comparison with that of T₃ and T₄.     

Immune responses to DNA vaccines

DNA vaccines, based on plasmid vectors expressing an antigen under the control of a strong promoter, have been shown to induce protective immune responses to a number of pathogens, including viruses, bacteria and parasites. They have also displayed efficacy in treatment or prevention of cancer, allergic diseases and autoimmunity. Immunologically, DNA vaccines induce a full spectrum of immune responses that include cytolytic T cells, T helper cells and antibodies. The immune response to DNA vaccines can be enhanced by genetic engineering of the antigen to facilitate its presentation to B and T cells. Furthermore, the immune response can be modulated by genetic adjuvants in the form of vectors expressing biologically active determinants or by more traditional adjuvants that facilitate uptake of DNA into cells. The ease of genetic manipulation of DNA vaccines invites their use not only as vaccines but also as research tools for immunologists and microbiologists. Received 26 October 1998; received after revision 3 December 1998; accepted 3 December 1998     

Occurrence of immunoreactive thyroglobulin in the parafollicular cells of dogs.

When the canine thyroid gland was stained by immunofluorescence and immunoperoxidase methods using undiluted thyroglobulin antiserum, a considerably stronger immunoreactivity was revealed in the parafollicular cells than in the colloid droplets and follicular cells. After induced hypercalcemia and antithyroid drug treatment, the immunoreactivity of the parafollicular cells coinciding with the movement of secretory granules containing calcitonin was conspicuously decreased. An application of diluted serum (above 1:10) produced a strong reaction in the colloid.     

The TSH receptor and its role in thyroid disease

The thyrotropin (TSH) receptor plays a preeminent role in thyroid physiology and disease. TSH, acting through the TSH receptor, is the major stimulator of thyroid cell growth, differentiation and function. In Graves' disease, the TSH receptor is the target of stimulating antibodies that cause hyperthyroidism. Although still a topic of debate, the TSH receptor has been implicated in the pathogenesis of the endocrine ophthalmopathy associated with Graves' disease. Blocking antibodies against the TSH receptor are involved in the development of hypothyroidism in a subset of patients with autoimmune hypothyroidism. Transplacental passage of stimulating or blocking TSH receptor antibodies from a mother with autoimmune thyroid disease may result in transient hyper- or hypothyroidism in early infancy. During pregnancy, the placental hormone human choriogonadotropin (hCG) can cause gestational hyperthyroidism through cross-reaction with the TSH receptor. Gestational hyperthyroidism may also be involved in the pathogenesis of hyperemesis gravidarum. Trophoblast tumors secreting hCG are a rare cause of hyperthyroidism. Somatic activating mutations of the TSH receptor have been identified as a molecular cause of toxic adenomas, whereas activating mutations in the germline give rise to nonautoimmune familial hyperthyroidism or sporadic congenital hyperthyroidism. These gain-of-function mutations are dominant, and one mutated allele is sufficient to result in disease. Inactivating germline mutations of both TSH receptor alleles lead to variable degrees of resistance to TSH, encompassing a spectrum ranging from euthyroid hyperthyrotropinemia to overt hypothyroidism with thyroid hypoplasia. Received 31 January 2001; received after revision 3 April 2001; accepted 3 April 2001     

TSH-receptor antibodies, HLA B8 and thyroid autoantibodies in patients with Graves' disease in therapeutically induced euthyroidism.

The prevalence of TSH-receptor antibodies and of thyroid autoantibodies was studied in 48 HLA-typed patients with Graves' disease, who were in an euthyroid state after antithyroid therapy with methimazole. TSH-receptor antibodies, which were found in 35% of the patients, did not correlate with the positivity of HLA B8. By contrast the persistence of thyroid microsomal antibodies was significantly associated with HLA B8.     

TSH-Receptor antibodies,HLA B8 and thyroid autoantibodies in patients with Graves' disease in therapeutically induced euthyroidism

Summary The prevalence of TSH-receptor antibodies and of thyroid autoantibodies was studied in 48 HLA-typed patients with Graves' disease, who were in an euthyroid state after antithyroid therapy with methimazole. TSH-receptor antibodies, which were found in 35% of the patients, did not correlate with the positivity of HLA B8. By contrast the persistence of thyroid microsomal antibodies was significantly associated with HLA B8.     

In vivo study of the hypocalcemic, hypophosphoremic, hyperlipemic, and immunogenic activities of the oligopeptide fragment common to ACTH, alpha and beta MSH, and beta lipotropin]

The intravenous injection that was given to rabbits which consisted of 0,5 mg of a common heptapeptide to ACTH4-10, BETA MSH11-17 hormones, and to beta lipotropic47-53 hormone (beta LPH47-53) was followed at the end of an hour by an augmentation of 70% of total lipids, and at the end of two hours by a lowering of calcemia (around 27%) and of phosphoremia (20%). The injection of a tetrapeptide corresponding to only ACTH7-10 bound to a nitrobenzylhydralamin and in presence of a Freund adjuvants has provoked the formation of corresponding antibodies.     

Aldolase C is localized in neuroendocrine cells

To elucidate the localization of the subunit C of aldolase (aldolase C) in peripheral neuroendocrine cells, we made an immunohistochemical study with monospecific antibodies against human aldolase C. Aldolase C was found to be localized in various types of neuroendocrine cells; in the pituitary gland, thyroid, pancreas, adrenal gland, bronchus, and gastrointestinal tract.     

Aldolase C is localized in neuroendocrine cells

Summary To elucidate the localization of the subunit C of aldolase (aldolase C) in peripheral neuroendocrine cells, we made an immunohistochemical study with monospecific antibodies against human aldolase C. Aldolase C was found to be localized in various types of neuroendocrine cells; in the pituitary gland, thyroid, pancreas, adrenal gland, bronchus, and gastrointestinal tract.     

Putting endotoxin to work for us: Monophosphoryl lipid A as a safe and effective vaccine adjuvant

The development of non-infectious subunit vaccines greatly increases the safety of prophylactic immunization, but also reinforces the need for a new generation of immunostimulatory adjuvants. Because adverse effects are a paramount concern in prophylactic immunization, few new adjuvants have received approval for use anywhere in the developed world. The vaccine adjuvant monophosphoryl lipid A is a detoxified form of the endotoxin lipopolysaccharide, and is among the first of a new generation of Toll-like receptor agonists likely to be used as vaccine adjuvants on a mass scale in human populations. Much remains to be learned about this compound’s mechanism of action, but recent developments have made clear that it is unlikely to be simply a weak version of lipopolysaccharide. Instead, monophosphoryl lipid A’s structure seems to have fortuitously retained several functions needed for stimulation of adaptive immune responses, while shedding those associated with pro-inflammatory side effects. Received 25 April 2008; received after revision 05 June 2008; accepted 10 June 2008     

Effects of thyroxine and exercise on the glandular and plasma levels of corticosterone in the male rat

Summary The results presented here demonstrates that the thyroid gland is essential for normal corticosterone production. They further show that exercise stimulates this production whether the thyroid gland is present or not. The release or metabolism of corticosterone seems dependent upon an intact thyroid gland since plasma levels of corticosterone are decreased during exercise if the thyroid is absent. The administration of thyroxine is not sufficient to renew these levels.     

Thyroid morphology and activity does not respond to ELF electromagnetic field exposures.

The hypothesis that the thyroid is the sensitive organ for extremely low freqency electromagnetic field effects was tested. Rats that had been exposed either preinatally or as adults to several intensities of 0.5 Hz magnetic fields displayed no significant alterations in thyroid morphology or circulating hormone measures.     

Thyroid morphology and activity does not respond to ELF electromagnetic field exposures

Summary The hypothesis that the thyroid is the sensitive organ for extremely low frequency electromagnetic field effects was tested. Rats that had been exposed either perinatally or as adults to several intensities of 0.5 Hz magnetic fields displayed no significant alterations in thyroid morphology or circulating hormone measures.Thanks to the technical staff of the Clinical Chemistry Laboratory at Laurentian Hospital.     

Composition and efficacy of iodothyronine immunogens and host responsiveness in radioimmunoassay (RIA) for serum thyroxine (T4)

Summary An immunogen was prepared consisting of iodinated and thyroxylated bovine thyroglobulin which on theoretical and practical grouds was highly specific for thyroxine; a rabbit antiserum derived from it fell within limits for RIA specification under conditions wherein a T4-BSA immunogen product was inactive.     

Generation of improved mucosal vaccines by induction of innate immunity

Vaccination is a highly effective means of disease prevention and has saved countless lives worldwide over the past 200 years. Traditional vaccines based on killed and attenuated organisms and inactivated toxins have constituted the majority of clinically used vaccines to date, but novel vaccines based on subunits of these organisms will be increasingly represented in future. In contrast to attenuated and whole cell vaccines, subunit vaccines do not generally contain immune-stimulatory components and are poorly immunogenic. As a result, new, potent and safe adjuvants and delivery systems are needed to enhance the immunogenicity of these vaccines. Furthermore, there is a drive to replace injected vaccines with those that can be administered by mucosal routes. Since the induction of innate immunity is crucial for vaccines to elicit potent antigen specific immune responses, a greater understanding of innate immunity at mucosal surfaces and the mechanism of action of adjuvants and delivery systems is required. Received 28 June 2005; received after revision 2 August 2005; accepted 30 August 2005     

Activation and inactivation of thyroid hormone by deiodinases: Local action with general consequences

The thyroid hormone plays a fundamental role in the development, growth, and metabolic homeostasis in all vertebrates by affecting the expression of different sets of genes. A group of thioredoxin fold-containing selenoproteins known as deiodinases control thyroid hormone action by activating or inactivating the precursor molecule thyroxine that is secreted by the thyroid gland. These pathways ensure regulation of the availability of the biologically active molecule T3, which occurs in a time-and tissue-specific fashion. In addition, because cells and plasma are in equilibrium and deiodination affects central thyroid hormone regulation, these local deiodinase-mediated events can also affect systemic thyroid hormone economy, such as in the case of non-thyroidal illness. Heightened interest in the field has been generated following the discovery that the deiodinases can be a component in both the Sonic hedgehog signaling pathway and the TGR-5 signaling cascade, a G-protein-coupled receptor for bile acids. These new mechanisms involved in deiodinase regulation indicate that local thyroid hormone activation and inactivation play a much broader role than previously thought. Received 29 August 2007; received after revision 11 October 2007; accepted 16 October 2007     

Effect of cold exposure on electrophysiological properties of rat heart

Male rats exposed to the cold (4°C) for five or ten days exhibited modifications in their thyroid state, as documented by increases in serum thyroid hormone levels, to which differently graded modifications of heart weight/body weight ratio, heart rate, and resting metabolic rate were associated. The values of the above mentioned thyroid state indicators returned to those of the control when the animals, kept at cold for ten days, were re-exposed to room temperature (24°C) for an additional 10 days. The configuration of action potentials, recorded in vitro at 26°C from fibres of anterior papillary muscles, was different in control rats of different age and was affected by prolonged cold exposure. In fact, the action potential duration (APD) increased after ten days of cold exposure. In the re-exposed group the APD was not different from that of the controls. Such a pattern was not significantly modified when the stimulation frequency increased from 1 Hz to 5 Hz. The above results suggest that in cold exposure, as in experimental hyperthyroidism, thyroid hormone might exert a cardiac chronotropic effect by modifying heart electrophysiological properties. Thus thyroid hormone should play a basic role during the exposure to cold environment, stimulating the body metabolism and increasing heart rate as a response to the requirement for greater tissue perfusion.     

Dietary immunostimulation: interaction with BCG and LPS.

The action of BCG and LPS mR595 used in conjunction with a formula-defined diet is dependent on the administration timing and resembles that of interacting adjuvants affecting different elements of the immune system.