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PubMed1992

The immune response evokes up- and down-modulation of beta 2-adrenergic receptor messenger RNA concentration in the male rat thymus.

Important alterations of noradrenergic activity are known to occur in specific brain regions and in different lymphoid tissues during the course of an immune response. Our recent characterization of the beta 2-adrenergic receptor (beta 2AR)-cAMP system of the rat thymus gland, the identification of a thymic beta 2AR gene expression, and the marked modulation of receptor mRNA concentration after castration and replacement with estrogen prompted us to study the ability of products of immune axis activation to modulate beta 2AR number, distribution, and expression in the male rat thymus. Moreover, the effect of adrenergic stimulation of adenylyl cyclase activity on thymus gland membrane preparations was measured. The beta 2AR present in the rat thymus undergoes marked changes in both number and distribution during the course of an immune response. At 3 days after antigenic challenge (injection of BSA in complete Freund's adjuvant), a sharp decrease of receptor number coupled with a significant loss of the autoradiographic reaction in the medullary compartment of the rat thymus gland were observed. These effects were followed by a significant increase in receptor density and number without changes in receptor affinity at 7 and 15 days post immunization, corresponding to the pick of the immune response. Parallel alterations in adenylyl cyclase activity were measured. Northern blot analysis, using a human beta 2AR cDNA as a probe, revealed dramatic alterations of the beta 2AR mRNA in the thymus, characterized by an approximately 75% decrease of mRNA level 3 days after immunization, and by a progressive increase at 7 and 15 days, with beta 2AR mRNA concentration rising to levels even higher than those found in control animals. These results suggest that the immune response evokes marked alterations of the thymic beta 2AR-cAMP signaling pathway. Moreover, antigenic stimulation triggers a down- and up-modulation of beta 2AR gene expression. Although it is presently unknown whether factor(s) released by immune axis activation act at the level of gene transcription to modulate adrenergic receptor function in the rat thymus, such down- and up-regulation of beta 2AR mRNA may play a role in the dynamic regulation of the immune response.

Adenylyl Cyclases↗
PubMed1969

Responses to immunization in the thymus of the adult mouse.

The rate of synthesis of RNA in the thymus glands of adult mice increased after immunization with sheep red blood cells (SRBC). The specific activity of some fractions of RNA, separated first by density gradient centrifugation and then by polyacrylamide gel electrophoresis, was 16-fold higher on day 3 after immunization than control mice not injected. RNA synthesis in the thymus was inhibited by rabbit anti-mouse thymus serum, injected along with antigen. A material was found in RNA extracts from the thymus glands of mice immunized with SRBC which converted a small proportion of either spleen cells or peritoneal cells from nonimmunized mice to form sheep cell hemolysins. Neither extracts from the glands of nonimmunized mice nor the livers of immunized mice were active. Extracts from the thymus glands of mice immunized with rabbit red blood cells (RRBC) were inactive and activity was destroyed by ribonudease. The residual antigen content was not determined. Biologically active extracts from the thymus had a different electrophoretic mobility from active extracts from the spleen.

Animals↗
PubMed2006

Role of the hypothalamic suprachiasmatic nucleus in the effect of melatonin on the thymus, adrenal glands, and spleen in rats.

We studied the role of the hypothalamic suprachiasmatic nucleus in realization of the effect of melatonin on stress marker organs in rats under normal conditions and during acute stress. Stress induced involution of the thymus in active rats and adrenal gland hypertrophy in active and passive animals. Electrocoagulation of the suprachiasmatic nucleus induced a more pronounced decrease in the weight of the thymus and greater increase in the weight of the adrenal glands. Melatonin administration after electrocoagulation of the suprachiasmatic nucleus had no effect on the relative weight of the thymus, adrenal glands, and spleen in control and stressed animals. The influence of melatonin on the thymus, adrenal glands, and spleen is partly mediated by this structure of the brain.

Adrenal Glands↗
PubMed1968

Prevention of wasting disease by pregnancy associated with hypertrophy of the fetal thymus.

Neonatally thymectomized female mice were studied and compared to appropriate controls. Neonatal thymectomy appears to decrease fertility significantly in the female C3H/HeJ mouse. However, if a thymectomized female mouse becomes pregnant, pregnancy offers significant protection against wasting disease and death. The maternal thymus appears to play no significant role in the development of the fetus as measured by gross examination and organ weights. Offspring of thymectomized females had comparable body and organ weights when compared to offspring from sham-operated females, except for the thymus gland and gastrointestinal tract. The absence of the maternal thymus gland did stimulate a significant increase in the gland weight of her offspring compared to sham-operated control female offspring. Parity, per se, in intact females also causes a significant increase in the weights of the thymus of newborn offspring.

Animals↗
PubMed1998

Thymus-dependent, anti-CD4-induced tolerance to rat cardiac allografts.

BACKGROUND: Treatment with anti-CD4 monoclonal antibodies (mAbs) leads to induction of transplant tolerance in rodent models, but the cellular mechanisms responsible are poorly defined. In this study, we used a rat model of cardiac transplantation to examine the contribution of the thymus gland to anti-CD4 mAb-induced tolerance. METHODS: Pretransplant administration of OX38 mAb partially depletes peripheral CD4 T cells and induces tolerance to fully allogeneic Lewis (RT1l) heterotopic cardiac allografts in DA (RT1a) recipients. Using this experimental model, the contribution of the adult thymus gland and of recent thymic emigrants to tolerance induction was assessed, and the cellular and humoral alloimmune responses accompanying tolerance defined. RESULTS: OX38 mAb selectively depleted mature CD4 T cells but spared CD4 T cells that had recently emerged from the thymus. Pretransplant thymectomy abrogated tolerance induction, but the data suggested a role for recent thymic emigrants rather than for the thymus gland per se. Both nonrejecting cardiac allografts in OX38-treated recipients and rejecting grafts in control animals were infiltrated to a similar extent by mononuclear cells, including activated T cells. Intragraft mRNA transcripts for interleukin (IL)-2, interferon-gamma, IL-4, IL-10, and IL-13 were similar in non-rejecting and rejecting allografts although, with the exception of IL-2, there was a trend towards reduced cytokine transcripts in tolerant grafts. CD4 T cells from long-term tolerant recipients proliferated normally to donor alloantigen in vitro, and produced IL-2, interferon-gamma, and IL-4 in amounts comparable to normal CD4 T cells. Tolerant recipients also developed a strong alloantibody response comprising both IgG1 (Th2-dependent) and IgG2b (Th1-dependent) subclasses. CONCLUSIONS: The results of this study suggest that the thymus, through the production of recent thymic emigrants, plays an important role in facilitating the induction of transplant tolerance after anti-CD4 mAb. Tolerant animals displayed strong cell-mediated and humoral alloimmune responses with no evidence of selective deviation from a Th1 to a Th2-like cytokine pattern.

Animals↗
PubMed1985

Attempts to implicate viruses in myasthenia gravis.

We investigated the hypothesis that a persistent viral infection of the thymus gland might trigger the autoimmune disease myasthenia gravis (MG). Thymus glands of nine patients with recent onset of MG were studied by a variety of techniques to detect the presence of occult viruses. No evidence of viral infection was found.

Adolescent↗
PubMedDate not supplied

Involution and neoplasms of the thymus.

Mammalian ontogenesis and postnatal histogenesis involves the dynamic and appropriate interaction of two growth related phenomena: progression and regression. The thymus gland is the organ of the mammalian body that exhibits the most profound involution during normal postnatal histogenesis. Involution of the thymus can be compared to similarly regressive processes during the ontogeny of holometabolic insects, as well as to the spontaneous regression of neoplasms. It can be expected that in the future a better understanding of neoplastic regression will result from the comparison of ontogenetic processes from taxonomically far-removed regressive processes, and the evaluation of various factors that promote progression and regression. Furthermore the thymus, as the key organ of the cellular arm of the mammalian immune system, is intimately involved in the determination of the eventual outcome of malignant neoplastic disease. Primary anterior mediastinal tumors comprise a diverse group of neoplasms accounting for 50% of all mediastinal tumor lesions. Thymic carcinomas and thymomas are epithelial neoplasms which can be divided according to clinical behavior into various biological subtypes. A review of the nature of thymic neoplasms, a description of physiologic and accidental involution of the thymus gland, and a discussion of various paraneoplastic disorders, including myesthenia gravis, associated with thymic neoplasms are the aims of this article.

Animals↗
PubMed1998

Thymectomy for myasthenia gravis.

The pathophysiological role of the thymus in myasthenia gravis, and the mechanism of therapeutic effect of thymectomy, are incompletely understood. Nevertheless, thymectomy is a valuable treatment modality in selected patients with generalised myasthenia gravis. There are several types of thymectomy operation, but no one operative approach is clearly superior to the others. Total removal of the thymus gland is essential. Additional excision of associated mediastinal and cervical tissue, that may harbor ectopic thymic rests, is a controversial surgical issue. Surgeons that advocate thymectomy through small, cosmetically favourable, incisions usually believe that simple removal of the thymus gland is an adequate operation. Surgeons that emphasise the importance of removing extrathymic tissue, in addition to the thymus gland, usually favour greater operative exposure through a median sternotomy. To minimise operative morbidity, surgery for myasthenia gravis requires a multidisciplinary (neurology, surgery, anaesthesia) approach to peri-operative care.

Humans↗
PubMed2006

Effect of melatonin on the thymus, adrenal glands, and spleen in rats during acute stress.

We studied the effects of acute stress and exogenous melatonin on stress marker organs in rats. Administration of melatonin under normal conditions increased the relative weights of the thymus (active rats) and adrenal glands (active and passive rats). The relative weight of the spleen also tended to increase after melatonin treatment. Stress led to involution of the thymus and hypertrophy of the adrenal glands in active and especially in passive animals receiving physiological saline. Melatonin partially or completely prevented involution of the thymus under stress conditions. Stress had no effect on the relative weight of the adrenal glands in melatonin-treated rats. The relative weight of the spleen in active rats receiving melatonin in doses of 0.5 and 1 mg/kg decreased after stress exposure. Our results suggest that melatonin modulates the hemodynamics and function of stress marker organs.

Acute Disease↗
PubMed1984

[Effect of polypeptide factors of the thymus, pineal gland, bone marrow and anterior hypothalamus on the realization of transplacental carcinogenesis].

The postnatal action of low-molecular polypeptide factors of thymus (FT), pineal gland (FP), bone marrow (FRM) and anterior hypothalamus (FAH) on transplacental carcinogenic effect of N-nitroso-N-ethylurea in rats was studied. Both FT and FP administrations decreased incidence and multiplicity of tumours and prolonged their mean latent periods. These drugs inhibited mainly the development of tumours of the spinal cord, kidneys and peripheral nervous system but not those of the brain. Both FBM and FAH had no significant influence on transplacental carcinogenesis. FT and FP anticarcinogenic effect is supposed to be due to their normalizing action on hormonal metabolic and immunological shifts arising in the body after transplacental administration of the carcinogen.

Animals↗
PubMed2004

Effects of bioactive factors of the pineal gland on thymus function and cell composition of the bone marrow and spleen in mice of different age.

The effects of factors from the pineal gland on the titer of thymic serum factor in the supernatant of 3-h thymus stroma cultures, number of stromal precursor fibroblasts and CD4+ cells in the bone marrow, and CD8+ cells in the spleens of adult and old CBA mice were studied in vitro. Epithalamin, Epithalon, and melatonin appreciably increased the titer of thymic serum factor in the supernatant of thymus stroma cultures from mice of different age and increased the percentage of CD4+ cells in the bone marrow suspension from old animals in vitro. The percentage of CD8+ lymphocytes decreased after incubation of splenic cells from old mice with melatonin. The percentage of bone marrow fibroblast precursor cells from adult and old mice did not appreciably change after incubation with the preparations.

Animals↗
PubMed1982

Moloney murine sarcoma virus tumors in CBA/J mice: chemopreventive and chemotherapeutic actions of supplemental beta-carotene.

Decreased tumor frequency, increased latent period, and increased rate of tumor regression were observed in male inbred CBA/J mice fed supplemental beta-carotene before and/or after they were inoculated with the Moloney sarcoma virus. When beta-carotene feeding was begun after tumors were already present, it markedly increased the rate of tumor regression. beta-Carotene minimized the virus-induced thymus gland involution that accompanies tumor growth, and this action on the thymus gland was believed to underlie part of beta-carotene's antitumor activity. The basal diet, a standard commercial mouse chow containing more vitamin A than the National Research Council recommends as a daily allowance for rodents, supported normal growth, reproduction, and longevity of normal mice. The work reported here is the first demonstration of the antitumor action of beta-carotene in mice inoculated with an oncogenic virus.

Animals↗
PubMed1974

Comparison of thymic histology with response to thymectomy in myasthenia gravis.

Fifty-four thymus glands removed surgically from patients with myasthenia gravis were examined using an accurate morphometric technique and the data compared with the response to thymectomy. There is a tendency for patients with relatively unreactive thymus glands to obtain a better result from thymectomy but this is not statistically significant.

Adolescent↗
PubMed1999

Thymic hyperplasia after high-dose chemotherapy and autologous stem cell transplantation: incidence and significance in patients with breast cancer.

OBJECTIVE: The purpose of this study was to determine the incidence and clinical significance of thymic hyperplasia after high-dose chemotherapy and autologous stem cell transplantation for treatment of metastatic or high-risk primary (with at least four positive lymph nodes) breast cancer. MATERIALS AND METHODS: We retrospectively reviewed clinical records and CT scans of 102 breast cancer patients treated with high-dose chemotherapy and autologous stem cell transplantation. Patients were 26-63 years old (mean, 46 years). The length and width of the thymus gland were measured on serial CT scans obtained before and after treatment. Moderate thymic hyperplasia was recorded if a focal or diffuse increase was seen in the oblong, triangular soft-tissue opacity conforming to the configuration of the normal gland within the anterior mediastinum after therapy. Minimal hyperplasia was recorded when a minimal increase was seen in soft-tissue attenuation conforming to the configuration of the normal bilobed thymus gland within the anterior mediastinum, but no discrete mass was visible. RESULTS: CT showed no thymic hyperplasia in 91 (89%) of the 102 patients. CT showed thymic hyperplasia in the other 11 patients (11%). Three patients (3%) had moderate hyperplasia, and eight patients (8%) had minimal hyperplasia. When comparing patients with and without hyperplasia, we found no difference in mean age or survival. CONCLUSION: Thymic hyperplasia is rare after high-dose chemotherapy and autologous stem cell transplantation in adult patients with metastatic or high-risk primary breast cancer. In this population, thymic hyperplasia does not appear to correlate with survival.

Adult↗
PubMed1988

Thymosin and the spontaneously diabetic BB rat.

The biological basis for autoimmunity and immunoincompetence in the BB rat has yet to be localized. In spite of normal thymic histology, thymocyte subsets and blastogenesis, thymus gland products (thymosins) have yet to be studied. In the present report, thymus gland function was studied by measuring thymosin alpha 1 levels at one time point in the BB rat compared with control rates, and BB rat responses to exogenous thymosin (Thymosin fraction 5) were observed. At five months of age, BB rats had thymosin alpha 1 levels comparable to Lewis and Wistar furth rats. Thymosin fraction 5 increased the ratio of peripheral blood W3/25 positive to OX8 positive cells, but otherwise had no effect on the BB rats' T-cell immunodeficiency, or frequencies of tissue autoantibodies or insulin-dependent diabetes. Although B-lymphocyte counts were normal in BB rats, splenocyte responses to B-lymphocyte mitogens were depressed. However, thymosin fraction 5 improved the BB rat B-lymphocyte blastogenesis to near normal for Mycoplasma neurolyticum. Coupled with our previous work, our results suggest that the immune derangement in the BB rat resides outside the thymus.

Animals↗
PubMed1977

Thymic lymphocytes in myasthenia gravis.

Lymphocytes from the thymus glands of myasthenic patients and controls were characterized in terms of their percentages of B- and T-cells and their ability to stimulate the proliferation of autologous peripheral blood lymphocytes. Percentages of B- and T-cells were the same in the thymuses of myasthenic and control subjects. Autologous peripheral lymphocyte stimulation by thymocytes was observed in only 1 of 3 myasthenic patients, and this was with a thymus gland containing a thymoma. These results thus differ from those of other investigators.

B-Lymphocytes↗