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PubMed1991

Role of a calf thymus preparation in the degradation of native and reductively methylated low density lipoprotein.

1. The clearance of low density lipoprotein (LDL) is mediated by a specific LDL receptor pathway and by an alternative metabolic pathway that is responsible for the receptor-independent LDL catabolism. 2. This alternative catabolism can be studied in vivo using a preparation of chemically modified LDL that are reductively methylated. 3. Recently we showed that a calf thymus protein extract affects the cholesterol metabolism via activation of LDL catabolism. 4. The aim of this study was to investigate whether in vivo the specific LDL receptor pathway and the independent LDL receptor pathway are affected by thymus treatment. 5. The results obtained injecting in rats native and chemically modified 125I-LDL to probe the receptor independent pathway, show that the thymus gland decreases serum cholesterol by activation of the specific LDL receptor pathway. 6. This effect is mainly evident in liver and kidney that represent organs in which the specific LDL receptors are widely present.

Animals↗
PubMed2002

The effect of thymectomy and IL-1 on memory: implications for the relationship between immunity and depression.

Macrophages produced proinflammatory cytokines and inflammatory responses can cause many symptoms of depression, including direct stimulation of the HPA axis and secretion of cortisol. In depressed patients, hypercortisolism has been well described as one of the major symptoms and also as the cause for hippocampal atrophy and memory impairment. In this paper, the relationships between thymectomy, increased IL-1 levels, and changes in corticosterone and neurotransmitter concentrations in rats are discussed, as well as their implications for memory impairments and depression. In thymectomized rats, deficits in both spatial and fear conditioned memory have been observed. Thymectomy decreases noradrenaline and dopamine levels, and increases serotonergic neurotransmission in limbic areas, without affecting corticosterone concentrations. In a depression model, thymopeptides or IL-2 treatment significantly attenuated changes in behavior, lymphocyte proliferation and neurotransmitters caused by bulbectomy. The reduction of thymic functions may increase IL-1 synthesis. Central IL-1beta administration impairs rat's spatial memory in the Morris water maze and 8 arms radial maze, but enhances conditioned memory in the passive avoidance. These changes can be reversed by either IL-1 receptor antagonist or a glucocorticoid receptor antagonist (RU 486). Furthermore, IL-1-induced changes in some neurotransmitter systems are similar to those observed in thymectomized rats. However, both acute and sub-chronic IL-1 administration increases plasma corticosterone concentrations. Together, these findings suggest that changes in the function of the thymus gland may play an important role in the unbalance between macrophages, cytokines, and lymphocytes, which induces neurotransmitter and neuroendocrine changes, and memory disturbances in depressive illness.

Animals↗
PubMed1979

Ultrastructural studies on erythropoiesis in the avian thymus. I. Description of cell types.

Thymus lobes from three species of birds, Quelea quelea, Passer domesticus and Sturnus vulgaris, have been examined ultrastructurally. The component cell types are compared with their counterparts in mammalian thymus glands, and found to be similar. Greater differences between small, intermediate and enlarged lobes of one species than exist between species. Developing erythroid cells are present in most enlarging and some enlarged glands. They appear to be developing at the expense of lymphoid cells in some birds. The origin of these cells is discussed. Cells that are possible candidates for the production of some thymic hormones are also described.

Animals↗
PubMed2001

The thymus. Finally getting some respect.

The thymus gland is no longer a structure in the anterior mediastinum of questionable use in the body economy. It is the sole source of cells that control the immune response and provide protection from life-threatening pathogens. Its primary function is to seed the periphery with mature T cells. Because these cells can maintain their numbers through self-replication, thymic function essentially is completed within the first few years of life. In response to a lack of need for its services, the thymus thereupon undergoes involution. A demand for renewed thymopoiesis has become necessary as the T-cell compartment of the immune system must be replenished following massive depletion of T cells by disease (e.g., AIDS) or the demands of cytoreduction necessary to achieve successful bone marrow transplantation. In older patients with AIDS (> 20-30 years), re-expansion of the post-thymic population may be adequate to restore the patient to reasonable or even normal T-cell immunity, but when the cytoablation is as massive as seen with bone marrow transplant conditioning regimens, the thymus must contribute to the repopulation. If involution has proceeded too far, thymic output must be augmented. This augmentation can be accomplished by thymus transplantation. The techniques for successful thymus transplantation in adults, however, have yet to be perfected. The thymus can play a major role in determining the response to MHC products of others (i.e., nonself). Novel manipulations of the thymus are being used to achieve transplant tolerance.

Adult↗
PubMed1987

Role of the thymus in histiocytosis-X.

An increasing number of reports have demonstrated that patients with histiocytosis-X show significant morphologic changes in the thymus gland. The changes include severe dysplasia, dysmorphia, and severe nonspecific involution. These findings are present in all children with histiocytosis-X who die, but can be found even when the disease is limited to one bone and is not fatal.

Age Factors↗
PubMed1980

Cervical thymic cysts in children.

Thymic cysts are a rare cause of cervical masses in children. The cysts usually appear between ages 6 and 7 years and present as a soft swelling in the anterior triangle of the neck. The cysts may be small and unilocular or large and multilocular; they produce few symptoms. The etiology is unclear but may be related to remnants of tissue left in the cervical region when the thymus gland descends from the neck to the mediastinum during embryologic development. Forty-three cases of cervical thymic cysts have been reported in patients under 20 years of age. Two additional cases are reported in boys 5 and 9 years of age.

Age Factors↗
PubMed1994

Characterization, expression, and hormonal control of a thymic beta 2-adrenergic receptor.

In the present study, we have characterized the beta 2-adrenergic receptor (beta 2-AR)-adenosine 3',5'-cyclic monophosphate (cAMP) system of the rat thymus gland and examined the hormonal regulation of the thymic beta 2-AR gene expression under physiological or pharmacological conditions accompanied by marked alterations of the sex steroid hormone milieu. We report here that membrane preparations of female rat thymic tissue contain iodocyanopindolol binding sites that exhibit pharmacological properties typical of a beta-AR. Detailed analysis by computer modeling of the binding potencies of a large series of beta 1- and beta 2-adrenergic agonists and antagonists revealed predominantly the beta 2-AR subtype (78%) in rat thymus. This inference from radioligand binding studies was corroborated functionally by the rank order of potencies of a series of adrenergic agonists to stimulate the production of cAMP. Northern blot analysis, using a human beta 2-AR cDNA as a probe, revealed the presence of a mRNA of 2.3 kb, which is consistent with the size of the beta 2-AR mRNA found in other rat tissues. Physiological regulation of specific beta 2-AR in the rat thymus was indicated by significant increases in both receptor concentration and steady-state levels of beta 2-AR mRNA during the diestrous 2 and proestrous phases of the rat estrous cycle and pregnancy, whereas castration sharply reduced beta 2-AR numbers and transcript levels within the thymus. The modulation of the thymic beta 2-AR-cAMP signaling system by the preexisting sex steroid milieu, coupled with the sex-dependent adrenergic modulation of thymic cell-mediated immune response, may contribute to the various sex-related alterations in immune responsiveness and could play a role in sexually related immune disorders.

Adenylyl Cyclases↗
PubMed1975

Breeding nude (nu/nu) mice.

By using as sires homozygous nude males bearing thymus glands from their normal siblings, heterozygous females yield 50 per cent nu/nu offspring under conventional conditions. Most nu/nu females are fertile, but in our experience only 20 per cent of them rear nude litters to weaning age.

Animals↗
PubMed1992

Structural relationships between two forms of DNA polymerase epsilon from calf thymus.

We previously reported purification of two forms of DNA polymerase epsilon from calf thymus (Crute, J. J., Wahl, A. F., and Bambara, R. A. (1986) Biochemistry 25, 26-36). We have now used the "polymerase trap" photolabeling method to identify the polypeptides containing the polymerase active site in each enzyme preparation. The molecular mass of these polypeptides are 210 and 145 kDa for the polymerases now designated epsilon and epsilon*, respectively. Renaturation of polymerase activity from denaturing gel electrophoresis corroborates the polymerase trap results. Photolabeling of polymerase fractions suggests that the smaller subunit is derived by proteolysis of the larger subunit during purification. Native sedimentation coefficient measurements of polymerase-containing column fractions further suggest a precursor/product relationship between the two polymerases. Response of polymerization activity to a battery of inhibitors normally used to distinguish mammalian nuclear DNA polymerases was found to be essentially identical for polymerases epsilon, epsilon*, and the epsilon* generated in fractions initially containing epsilon. These latter results demonstrate that the loss of the protease-sensitive domain of the active site subunit does not affect catalytic function as measured in a standard DNA polymerase assay. The sole apparent functional difference observed here between the epsilon and epsilon* forms is evidence that only the full-length epsilon form can be directly photocrosslinked to dATP, independent of DNA synthesis. Photolabeling of the post-microsomal supernatant fraction from thymus glands obtained from fetal calves reveals the presence of both the epsilon and epsilon* polypeptide.

Animals↗
PubMed1991

Effects of early partial decapitation on the ontogenic development of chicken lymphoid organs. I. Thymus.

For the present study we used the classic model of early partial decapitation (DCx) of chicken embryos (Fugo, J. Exp. Zool., 85: 271-298, 1940; Betz, Gen. Comp. Endocrinol., 9: 172-186, 1967) in an attempt to analyze the neuroendocrine immune relationships during ontogeny. The elimination of the prosencephalon in chickens at 33-38 hr of incubation induced profound structural, histochemical, and morphometric changes in the embryonic development of the thymus gland. These included a greater development of the cortex than of the medulla, an increased mitotic index, high numbers of pyknotic cells, and enlarged connective tissue trabeculae containing numerous large lymphoid cells; hypertrophied reticular-epithelial cells; delayed appearance of medullary epithelial cysts; and intrathymic granulopoiesis. Furthermore, preliminary radioimmunoassays revealed a sharp increase in the values of circulating thymic hormones, mainly thymosin beta 4 in 17-day-old embryos. The results are discussed with regard to the possible role of prolactin, thyroxine, testosterone, and thymic hormones in the ontogenic development of the chicken thymus.

Adenosine Triphosphatases↗
PubMed1990

Atrial natriuretic peptide is synthesized in the human thymus.

Various neuropeptides have recently been isolated from the thymus, suggesting an interaction between the neuroendocrine and immune systems. We report here that the human thymus synthesizes a further peptide hormone, namely atrial natriuretic peptide (ANP). This is documented by the following findings. ANP and its prohormone were detected in thymic tissue by chromatographic analysis as well as by RIA; the thymus gland and, in particular thymocytes, contain mRNA coding for ANP. Since ANP is common to the brain and the immune system, these data support the notion of the existence of a neuroendocrine-immune axis.

Atrial Natriuretic Factor↗
PubMed1999

Microchimerism in thymus is associated with up-regulated T helper type 1 cytokine transcription during cardiac allograft rejection in rats.

BACKGROUND: Intrathymic microchimerism (MC) is thought to be responsible for inducing allograft tolerance. However, the role of MC in the thymus gland after transplantation, particularly in the rejection response, is unknown. We investigated serial changes in intrathymic cytokine production associated with MC and allograft rejection. METHODS: Donor-specific cell injection (DSI) and heterotopic heart transplantation (HTx) were performed in the fully allogeneic combination using DA rats (RT1a) as donors and WS rats (RT1k)as recipients. MC was checked by polymerase chain reaction (PCR) using a donor RT1.Bbeta domain 1 region sequence-specific primers. Reverse transcription (RT)-PCR analysis of cytokine (interleukin [IL]-2, interferon-gamma, IL-4, and IL-10) profiles of the thymus was performed in animals given DSI, HTx, or DSI/HTx. RESULTS: DSI alone resulted in an immediate development of MC, detected by PCR, in various organs including the thymus, spleen, liver, and blood, of most rats, lasting for over 2 months. However, DSI-induced MC selectively disappeared in the thymus on day 7 after grafting, several days before the rejection of cardiac allograft. RT-PCR analysis of cytokine profiles showed that the levels of Th1 (IL-2 and interferon-gamma) cytokines transcribed in the thymus were higher than in the spleen. MC reappeared in the thymus on day 21 after grafting, but was not associated with elevation of Th1 cytokine transcription when allograft was replaced by fibrosis. CONCLUSIONS: Intrathymic MC does not always confer unresponsiveness to alloantigen, but can be eliminated after anti-donor response.

Animals↗
PubMed2006

Fatal Candida tropicalis infection in an 8-month-old infant with an aplasia of the thymus as a rare cause of death in infancy.

UNLABELLED: Anomalies of the thymus can lead to immunodeficiencies that are often associated with complex syndromes. The clinical relevance of those anomalies varies a lot. Regarding mortality and morbidity, opportunistic infections play a major role in immunocompromised individuals. CASE REPORT: An 8-month-old infant died of a sepsis with multi-organ failure after 32 days in intensive care. At autopsy, no thymus gland could be found; toxicological examinations yielded high morphine concentrations. Autopsy findings and the results of further examinations performed postmortem are discussed in view of the clinical findings, the classification and the cause of death.

Analgesics, Opioid↗
PubMed2005

[A technique of videothoracoscopic thymectomy in diseases of the thymus].

Intensive development of thoracoscopic thymectomy (Tthy) has been initiated during the last decade. Unfortunately very few instances of using the procedures have been described in Russian medical literature. So, the paper describes in detail the technique and results obtained in our clinic. At the period from 1998 through 2004 37 Tthy operations were performed in the St. Petersburg Center of intensive pulmonology and thoracic surgery. There were 21 female and 15 male patients with mean age 41.5+/-18.9 years. Myasthenia gravis (MG) was diagnosed in 19 of those patients. Different thoracoscopic approaches were used for Tthy: 20 from the right side, 15 from the left side and 2 combined approaches with neck incision. In 2 cases when invasive thymoma was suspected, sternotomy had to be used. There were 6 postoperative complications (1 haemothorax and 5 myasthenia cases). One patient died in 45 days after operation because of the ventilation-associated pneumonia. The results of treatment were followed up in 34 patients during 6-34 months. The MG course was followed up in 17 out of 19 patients, 9 (52.9%) being asymptomatic, 6 (35.3%) improved and 2 (11.8%) stable. Tthy is a novel technical possibility for a removal of the thymus gland. The procedure is quite safe and radical in the hand of a surgeon experienced in mediastinal and thoracoscopic surgery. Treatment of thymoma using Tthy requires meticulous technique and longer follow-up.

Adolescent↗
PubMed1984

Dependence of thymus development on derivatives of the neural crest.

Elimination of limited areas of the cephalic neural crest in stage 9 or 10 chick embryos markedly reduced the size of the thymus gland or resulted in its absence. Small thymic lobes contained both thymocytes and epithelial cells but showed delayed development. Parathyroid and thyroid glands sometimes were reduced in size or missing from the normal location on one or both sides. Heart defects were consistently present. Thymus development may depend on direct interaction of mesenchymal derivatives of the neural crest with pharyngeal epithelium. Multiple defects, such as the Di George syndrome, may result from failure of neural crest derivatives to migrate and interact properly.

Animals↗
PubMed1983

Progesterone receptors in rat thymus.

Tritiated promegestone ([3H]R5020) is bound with high affinity in cytosol prepared from the thymus gland of both male and female rats. To prevent tracer binding to glucocorticoid receptors, we have used excess RU26988 (11 beta, 17 beta-dihydroxy-21-methyl-17 alpha-pregna-1,4,6-trien-20-yn-3-one), a highly specific synthetic glucocorticoid. In the presence of 1 microM RU26988, [3H]R5020 was bound with high affinity (Kd less than or equal to 1 nM) and specificity (R5020 greater than progesterone much greater than estradiol greater than dihydrotestosterone = cortisol = corticosterone = dexamethasone) appropriate for progesterone receptors (PR). These sites were predominantly located in the epithelioid fraction of the thymus. PR levels were 14 +/- 3 fmol/mg protein in female thymus and 10 +/- 4 fmol/mg in male thymus; estrogen administration elevated thymic PR levels in both species (female, 26 +/- 2 fmol/mg; male, 21 +/- 3 fmol/mg). In estrogen-primed female rats, cytosolic thymic PR levels were acutely lowered to 20% of estrogen-primed control levels by the im administration of 1 mg progesterone. Thymic PR levels in pregnant (11-14 days) rats were approximately 50% of those in nonpregnant controls. Effects of glucocorticoids, androgens, and estrogens on the thymus are well documented; the demonstration of PR raises the possibility of direct effects of progesterone on the thymus.

Androstanols↗
PubMed1990

Dual-label retrograde transport: CNS innervation of the mouse thymus distinct from other mediastinum viscera.

Two different retrogradely transported tracers were identified and used to distinguish between the innervation of the thymus gland and the innervation of adjacent tissues residing within the mouse mediastinum. To determine the best procedure for peripheral dual-labeled retrograde transport, several different tracers, vehicles, and injection protocols were developed and/or tested. In the periphery, it proved ineffective to use Rhodamine latex microspheres (Luma-Fluor) as a retrograde transport agent. Horseradish peroxidase (HRP) suspended in the water-soluble carrier KY Jelly and Fluoro-Gold (FG) in an aqueous solution was the most effective combination of retrograde transport tracers. Equivalent doses of each of these tracers were determined, and injections of HRP or FG into the thymus and the esophagus produced distinct and separate patterns of labeled neurons in the spinal cord or brain stem. Throughout these CNS areas, some neurons contained both tracers suggesting that 1) these areas are innervated by neurons that give rise to collaterals to these tissues, 2) that the retrograde tracers are transported by nerves that innervate the lymphatics of the mediastinum, and/or 3) that some diffusion of the tracers occurs from the test organs and tissues to other organs and tissues of the mediastinum.

Animals↗
PubMed1979

Diagnostic dilemma of a 13-month-old boy with 'late-onset' combined immunodeficiency.

A 13-month-old boy had a "late-onset" form of combined immunodeficiency and a fulminant Pneumocystis carinii pneumonia of one month's duration. There was no evidence of cutaneous-delayed hypersensitivity responses to diphtheria-tetanus toxoids, Candida albicans, or streptokinase-streptodornase, or of lymphocyte DNA synthesis after in vitro stimulation with the mitogens phytohemagglutinin and concanavalin A, and only 2% to 4% of peripheral blood E-rosetted T lymphocytes. The serum IgM level was normal (62 mg/dL), whereas the other immunoglobulins were markedly reduced. Despite an increased number of Ig-bearing lymphocytes, in vitro Ig secretion after pokeweed mitogen stimulation was substantially reduced. The thymus gland was dysplastic with no Hassalls' corpuscles or thymocytes, and other lymphoid organs showed depletion of T-dependent areas to a greater extent than the B-dependent areas.

B-Lymphocytes↗