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Samples of normal human thymus of different ages (4-63 years old) were studied by immunofluorescence microscopy (using antibodies to smooth muscle myosin, to actin from the chicken gizzard, and antibodies to myosin from human striated muscle) as well as by routine electron microscopy. Thymus tissue from myasthenia gravis patients was also investigated for comparative reasons. Epithelial cells reacted with anti-smooth, but not with anti-striated muscle myosin, whereas myoid cells reacted with antibodies to striated, but not to smooth muscle myosin. Both epithelial and myoid cells displayed a strong immunoreactivity with antiactin. Corresponding to this immunoreactivity, both cell types contained bundles of thin, actin-like filaments. Myoid cells occurred in the rounded and elongated variety, and they were a normal constituent of all thymuses investigated in this study. Ultrastructurally, this non-innervated, striated muscle-like cell type possessed bundles of thin and thick filaments as well as Z lines in a rather disorganized arrangement, resembling striated muscle after denervation or various other pathologic conditions. There were no overt differences in the number and structure of myoid cells between healthy and myasthenic patients.
Virchows Arch B Cell Pathol Incl Mol Pathol 1979 Dec
PMID:Myosin and actin containing cells in the human postnatal thymus. Ultrastructural and immunohistochemical findings in normal thymus and in myasthenia gravis. 4 51

The energy metabolism of rat thymus cells has been investigated using preparations of isolated cells obtained by mechanical treatment of whole organs. The addition of glycolytic substrates such as glucose, pyruvate and lactate stimulates the endogenous respiration of these cells by 50%. On the other hand, succinate, glutamate and malate do not produce any effect. Oligomycin (10 mug/ml) inhibits both endogenous and glucose stimulated respiration by about 40%; 2, 4-DNP (50 muM) increases by 100% glucose induced respiration. The results obtained by using mitochondrial and glycolytic inhibitors as well as aminoxyacetic acid (AOA) and following pyridine nucleotides redox changes, support the idea that in thymus cells glucose is able to induce a great enhancement of O2 consumption both by raising the level of endogenous pyruvate and feeding the mitochondrial respiratory chain with cytosolic reducing equivalents, through an active malate-aspartate shuttle. Thymus cells exhibit a high Pasteur effect (74%). Both AOA and 2,4 DNP are able to stimulate aerobic lactate accumulation by 200% and 100% respectively, indicating that either the redox or phosphate potential do influence the rate of aerobic glycolysis in isolated thymus cells. Similar experiments are also reported on other cells with well known biochemical characteristics.
Mol Cell Biochem 1975 Jul 31
PMID:Energy metabolism of isolated rat thymus cells. 24 Oct 10

Glucocorticoid (GC) treatment is known to induce destruction of cortical thymocytes and then their reconstitution. By using the rats treated with GC, we examined the relationship between rosette-formation and surface markers (CD4 and CD8) for clarifying the processes of differentiation and maturation in rat thymocytes. Thymus weight and thymocyte count began to decrease immediately after GC administration and became minimal on 5-7 days, followed gradual recovery. The percentage of rosette-forming thymocytes began to decrease immediately after GC treatment and became minimal on 5 days, followed by recovery to the normal level by the 10th to 14th day after treatment. During the analysis of the changes in the percentage of 4 subsets (CD4-8-, CD4+8+, CD4+8+, CD4-8+) of rat thymocytes after GC treatment, the percentage of CD4+8+ cells was found to change in close relation to the change in the percentage of rosette-forming lymphocytes, suggesting that rosette-forming thymocytes are CD4+8+ cells. These results suggest that the treatment induces destruction of GC-sensitive thymocytes, possibly rosette-forming cells, followed by migration of precursor T cells (CD4-8- cells) in the thymus, and that the precursors change into rosette-forming cells (CD4+8+ cells) in the thymus, followed by differentiation and maturation into non-rosette-forming cells (CD4+8- or CD4-8+ cells).
Cell Mol Biol 1991
PMID:Surface characteristics of thymocytes in glucocorticoid treated rats using rosette-formation technique and surface marker analysis. 177 21

The dynamic process in rat thymocyte restoration after their destruction by glucocorticoid (GC) administration was examined. Thymus weight and thymocyte count became minimal 4-5 days after the administration. Then the thymus took a course of recovery. Endogenous DNA synthesis in thymocytes, reflecting their proliferation within thymus, decreased for 4 days but began to increase 6-8 days after GC treatment. Thymocyte responsiveness to soybean lectin (SBL), a possible stimulator for T-cell-precursors, showed elevation 4-5 days after the treatment. A marked decrease of lymphocytes in the cortex and unclearness of cortico-medullary junction were observed 2-3 days after GC treatment. Clusters of small lymphoid cells, which possibly contained SBL-responding cells, were found in the subcapsular area 4 days after the treatment and successively, large lymphocytes became visible in the same area. Thereafter, small lymphocytes in the cortical mid and deep zones increased, and cortico-medullary junction was restored. These histological features are discussed from the view of correspondence with the dynamic changes of endogenous DNA synthesis and SBL responsiveness in the thymocytes after GC administration.
Cell Mol Biol 1990
PMID:Rat thymus reconstitution after thymocyte destruction by glucocorticoid treatment--from the view of endogenous DNA synthesis and soybean lectin responsiveness in thymocytes. 208 23

Thymic epithelial cells appear to release the humoral factors endowing precursors of T cells (thymus-dependent lymphocytes) with the capacity to differentiate and maturate into relatively mature T cells. We have separated the polypeptide fractions containing these factors from the culture supernatant of thymic epithelial cell line. Thymus is reported to be innervated by autonomic nervous system from the prenatal to the pubertal period. But the physiological significance of the nervous system in this lymphoid organ remains obscure. And the modulator of the epithelial cell functions, namely, production and release of the bioactive polypeptides have never been clarified. We show here that acetylcholine (Ach) or carbamylcholine (Cch) enhanced the proliferation of thymic epithelial cells from the TAD3 cell line at preconfluent state, and the protein synthetic activity at confluent state. This phenomenon was completely suppressed by the pretreatment of alpha-bungarotoxin (alpha-BTx). These results suggest that nicotinic Ach-receptors exist on the epithelial cell surface membrane and that the differentiation and maturation of thymic lymphocytes are indirectly regulated by the activated functions of thymic epithelial cells stimulated with cholinergic agonists.
Cell Mol Biol 1989
PMID:Effects of cholinergic agonists on the proliferation and protein synthesis in a cultured thymic epithelial cell line. 262 6

Thymus and thymocytes peroxidizability was studied in well defined conditions where lipid hydroperoxide dependent peroxidation occurs. The results show that: (i) lipid peroxidation is very low in thymocytes notwithstanding the higher content of arachidonic acid; (ii) the amounts of lipophilic chain-breaking antioxidants is higher in thymocytes; (iii) the thymus contains more total lipids and phospholipids. Thus the higher sensitivity to peroxidation of the thymus can be due to the replacement of thymus parenchyma by fatty tissue not correlated to an increase of lipophilic antioxidants.
Biochem Mol Biol Int 1993 Apr
PMID:Relative susceptibility of the thymus and thymocytes to lipid peroxidation. 850 37

Two kinds of thymus epithelial cell lines have been utilized: the TAD3 from lymphocyte-dominant rat thymoma and the IT-45R1 derived from normal rat thymus. In the preconfluent state, the percent increase of DNA synthetic activity of TAD3 cells stimulated by GH or IGF-I was significantly higher than that of IT-45R1 cells. In the confluent state, at the contrary, no any noticeable modification of the activity by GH could be detected and that in both cell lines. However, a treatment of the confluent TAD3 cells with IGF-I caused a significant increase of their DNA synthetic activity, whereas the confluent IT-45R1 cells treated with these molecules did not. It was observed that TAD3 cells in the preconfluent state proliferate markedly after stimulation by GH or IGF-I as compared with IT-45R1 cells and that the former is able to proliferate even in the confluent state, after an exposure of IGF-I, whereas the latter did not. Thymus epithelial cells treated with GH were reported to release more IGF-I molecules what had as a consequence a marked proliferative response of thymic lymphocytes. It is therefore assumed that the very particular nature of TAD3 cells treated with IGF-I, able of proliferating by crossing over the contact inhibition, might have a close relationship in the formation of the lymphocyte-dominant thymoma.
Cell Mol Biol (Noisy-le-grand) 1997 Mar
PMID:Marked differences in proliferative response to stimulation of growth hormone and insulin-like growth factor-I between thymoma- and normal thymus-derived epithelial cell lines. 913 May 99

Thymus weight and total thymic lymphocyte (TL) number decreased markedly after hypophysectomy (HX). Serum level of insulin-like growth factor-I (IGF-I), one of mediators brought about by growth hormone (GH), reduced considerably after the operation. Exogenous GH stimulation enhanced significantly DNA synthetic activity of TLs from HX group only at lower cell concentrations, less than 5 x 10(5) cell/ml. However, there was not a significant difference in the percentage increase of the TL-DNA synthetic activity with exogenous GH between HX and sham-operated (SO) groups. Since GH-responding TLs appeared to be mature cells and to exist in thymus medulla, the results suggest that rate of the responding cells in the thymus medulla of HX animals is similar to that of SO ones. Furthermore, there was not a significant difference in the percentages of rosette-forming cells and non-rosette-forming cells, reflecting nearly the maturation steps of TLs, between groups. It is difficult to explain such an aspect in spite of severe reduction of TLs after hypophysectomy, since the proliferative-responding rate of TLS to exogenous GH stimulation and the constitutive ratio of each maturation step of TLs in the HX group were almost same as those of SO group. The contradictory data found in thymus after hypophysectomy are discussed from the point of view of the compensatory effects of growth hormone-releasing hormone on TLs from the operated animals.
Cell Mol Biol (Noisy-le-grand) 1997 Jun
PMID:Effect of exogenous growth hormone on in vitro proliferation of thymic lymphocytes from the hypophysectomized rats. 922 Jan 50

Recent studies in mice and humans show that the importance of the thymus extends well beyond the initial seeding of the peripheral T-cell pool. Although peripheral homeostasis can maintain T-cell numbers, the thymus is the major, if not the exclusive, source of new T-cell specificities. With age, thymus atrophy dramatically reduces the export of new T cells and predisposes an individual to impaired T-cell function, reduced T-cell immunity, and increased autoimmunity. Thymus atrophy is also the primary obstacle to restoration of the T-cell pool in the aftermath of HIV treatment or lymphoablative therapies. Here, we review thymus T-cell production, with particular attention to the factors that influence thymocyte export, and examine the impact that recent thymic emigrants have on the peripheral pool. In the future, thymic regeneration might become a feasible and potentially powerful approach to rejuvenating a depleted peripheral T-cell pool.
Trends Mol Med 2002 Oct
PMID:Thymic regeneration: teaching an old immune system new tricks. 1238 69

Adrenomedullin (ADM) is a hypotensive peptide, which derives from the proteolytic cleavage of pro(p)ADM and acts via two main subtypes of receptors, referred to as L1-receptor (L1-R) and calcitonin-receptor-like receptor (CRLR). While L1-R is selective for ADM, CRLR may bind either calcitonin gene-related peptide (CGRP) or ADM depending on the expression of the subtype 1 or the subtypes 2 and 3 of a family of chaperones, named receptor-activity-modifying proteins (RAMPs). There is evidence that ADM, in addition to regulating blood pressure and water and electrolyte balance, may be also involved during embryogenesis in the growth and differentiation of organs and tissues, especially of those where strong mesenchymal-epithelial interactions take place. Thymus is a linfo-epithelial organ, which undergoes a very rapid prenatal and postnatal growth, playing a pivotal role in the development of immunological defense. Hence, it appeared worthwhile to investigate the expression of ADM system in the newborn (3-day-old) rat thymus as compared to adult (3-month-old) animals. Reverse transcription (RT)-polymerase chain reaction (PCR) allowed the detection of the specific mRNAs of pADM and peptidyl-glycine alpha-amidating monooxigenase (PAM), the enzyme which converts immature ADM to the mature peptide, in both newborn and adult rat thymuses. PAM expression was markedly higher in newborn animals, which accords well with the more elevated concentrations of ADM measured by RIA in newborn than adult rat thymuses. L1-R, CRLR, RAMP1 and RAMP2 mRNA were detected in both groups of rats, and with the exception of RAMP1, the expression was markedly higher in newborn than adult rat thymus. RAMP3 mRNA was present only in the thymus of newborn animals. Collectively, the present findings indicate that ADM system is up-regulated in newborn rat thymus, thereby making it likely that ADM may be involved in the thymus growth and in the development of immunological defense mechanisms.
Int J Mol Med 2002 Dec
PMID:Differential expression of adrenomedullin and its receptors in newborn and adult rat thymus. 1243 5


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