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Enhanced DNA fragmentation in the thymus of spontaneously hypertensive rats.

The mechanisms contributing to organ injury in hypertension have been incompletely defined. The thymus gland of the spontaneously hypertensive rat (SHR) shows significant atrophy at the age of 15 wk compared with its normotensive control, the Wistar-Kyoto rat (WKY). The aim of the present study was to examine the thymus of SHR for evidence of DNA nicking as one of the mechanisms for thymic atrophy. SHR and WKY were subjected to adrenalectomy or sham surgery at 12 wk and studied at 15 wk. Adrenalectomy served to normalize the blood pressure in the SHR. DNA nicking was detected by in situ nick-end labeling (ISEL) of fixed tissue sections. Tissue sections were treated with proteolysis, and terminal deoxyribonucleotidyl transferase was used to incorporate biotinylated deoxynucleotides into DNA nick end in situ. Separately, DNA fragmentation was evaluated by measuring the level of released mono- and oligonucleosomes to the cytoplasm. A higher number of thymic ISEL-positive cells and a higher level of cytoplasmic mono- and oligonucleosomes were observed in SHR than in WKY. After adrenalectomy the enhanced level of ISEL and cytoplasmic mono- and oligonucleosomes in SHR was reduced to the level in WKY. Dexamethasone treatment (0.05 mg. kg-1. day-1) in WKY serves to decrease the thymus weight and significantly elevate the level of mono- and oligonucleosomes. Thus increased DNA fragmentation represents one of the mechanisms associated with thymic atrophy, a feature that reflects immune suppression in SHR.

Adrenalectomy↗

[Morphofunctional changes in the thymus of semisyngenous chimeras during the "graft versus host" response].

Activation of the enzymatic processes in the thymus cells was noted in the thymus gland at the early stages of the "transplantat-versus-host" reaction; the later stages were attended by inhibition of metabolic processes and reduction in number of immature and mature thymocytes in the cortical substance of the thymus. Besides, the cortical substance displayed accumulation of mesenchymal macrophages rich in lysosomal enzymes, particularly in the subcapsular layer where small foci of destruction formed at the late stages of the reaction.

Acid Phosphatase↗

Ovarian development in athymic nude mice. II. The growth of the oocyte and follicle.

Congenitally athymic mice homozygous for the Mendelian recessive mutation "nude" develop well defined morphological and quantitative changes in the ovarian follicle population. A decline in follicle numbers at 2 months of age is preceded by a retardation in follicle growth at 1 month of age. The growth of the oocyte and its nucleus are not affected by the nude mutation. However, the rate of growth and maximum size of the oocyte nucleolus are reduced in nudes. These developmental events are discussed in relation to the genetic activity of the oocyte, the role of pituitary gonadotrophins in follicular and oocyte growth and the possible role of the thymus gland in these processes.

Animals↗

[Activation of protein biosynthesis in rat organs and tissues during stimulation of the mononuclear phagocyte system with prodigiosan].

As shown earlier, the mononuclear phagocyte system (MPS) plays an important role in regulation of protein synthesis in different rat tissues. In vivo stimulation of MPS by lipopolysaccharide from Bacillus prodigiosum caused a significant increase of protein synthesis in the liver, lungs, adrenal glands, thymus, spleen and bone marrow. The results obtained suggest that MPS is involved in the regulation of tissue regenerative process at the level of physiological state.

Adrenal Glands↗

Estrogen blocks early T cell development in the thymus.

PROBLEM: Pregnancy and estrogen are known to suppress B lymphopoiesis as well as lead to thymic involution in the mouse. Additionally, estrogen deficiency by oophorectomy reportedly causes a selective increase in the B220+ B cells in the murine bone marrow. The purpose of this study was to determine if estrogens played a regulatory role in T cell development. METHODS: The first experimental group consisted of 5-6-week-old Balb/c mice that received subcutaneous pellets of placebo, estriol, estradiol, or progesterone. The thymus glands were examined 2-4 weeks after treatment. The second group consisted of 6-week-old Balb/c mice who underwent either bilateral oophorectomy or a sham procedure. Two weeks after the surgery, extensive phenotypic characterization of the thymus and spleen cells was performed by flow cytometry using monoclonal antibodies to surface markers of T cell subsets. RESULTS: Estrogen treatment causes a dramatic reduction of thymic size and cellularity. All defined T cell subsets of CD4 and CD8 were reduced, with a disproportionate loss of CD4+CD8+ double positive cells. Examination of the triple negative (CD3-CD4-CD8-) subset revealed a striking loss of TN developmental progression of the early precursor cells. Based on the expression of CD44 (pgp-1) and CD25 (IL-2R alpha) markers, the TN thymic compartment was composed almost entirely of the earliest population (CD44+, CD25-), with the remaining maturational stages (CD44+, CD25+; CD44-, CD25+; CD44-, CD25-) depleted. In contrast, all T cell developmental stages in the thymus were found to be in normal proportions in the oophorectomized mice, with no differences in the splenic T and B cell subsets. CONCLUSIONS: The study demonstrates that estrogen but not progesterone blocks T cell development in the thymus. However, contrary to our expectation, estrogen deprivation by oophorectomy does not enhance T cell development.

Animals↗

Ovarian development in athymic nude mice. The size and composition of the follicle population.

Mice homozygous for the Mendelian recessive mutation nude show a reduction in the size and changes in the composition of the ovarian follicle population. Follicular loss was first evident at 2 months of age and was specifically due to a reduction in the numbers of small (primordial) follicles and medium follicles in the initial growth stages. The first ovulation was delayed until 2 1/2 months of age. By 4 months an overall reduction in all fractions of the follicle population had occurred and ovulation had ceased. These developmental changes are discussed in relation to the role of the thymus gland in sexual maturation and reproductive function in the female mouse.

Animals↗

Multiple Langerhans cell nodules in an incidental thymectomy.

The isolated appearance of Langerhans cell histiocytosis in the thymus is quite rare. We report the finding of multiple small Langerhans cell nodules in the thymus of an 11-month-old infant who had undergone thymectomy in the course of surgical correction of tetralogy of Fallot. The subtle appearance of some of these nodules and aggregates was unlike the pattern of massive thymic infiltration seen in 7 previously reported cases of thymic Langerhans cell histiocytosis in childhood. This difference led us to consider whether these aggregates might be common in the thymus but overlooked in thymus glands removed incidental to cardiac surgery. We examined histologic material from 22 sequential thymectomy specimens removed during cardiac surgery from infants and children. None (0/22) had cohesive aggregates of Langerhans cells, as were seen in the index patient's thymus. Our patient's small thymic nodules resemble more closely a pattern found in adult patients with myasthenia gravis who have been incidentally shown to have Langerhans cell histiocytosis.

Adolescent↗

Steroid hormone receptors in the thymus: a site of immunomodulatory action of melatonin.

1. Melatonin and glucocorticoids are known to affect the immune response in an opposite mode. The probability for an interaction between these hormones in the thymus gland has been investigated in rats following chronic administration of exogenous melatonin and long-term exposure to variable levels of circulating glucocorticoids. 2. Daily melatonin administration was shown to affect the properties of corticosterone and progestin receptors in the thymus in the presence of normal and increased systemic corticosterone concentrations, but not in adrenalectomized animals. 3. In intact rats melatonin caused a marked increase in the affinity and a decrease in the density of thymic receptors for adrenal steroids. Following corticosterone overdosage, simultaneously with melatonin treatment, a decrease in receptor affinity and a relative increase in the number of binding sites was observed. 4. The results suggest that steroid hormone receptors in the thymus might be considered as a target site for the interaction between melatonin and adrenal steroids in the modulation of the immune response.

Adjuvants, Immunologic↗

Effect of gonadectomy on isoproterenol-induced myocardial infarction.

Adult male and female Sprague-Dawley rats were subjected to an isoproterenol-induced myocardial infarction. Six weeks before the induction of myocardial infarction, some of the animals had been orchiectomized or ovariectomized. The animals were autopsied at regularly timed intervals on days 1, 2, 3, 8, and 15 after myocardial infarction. The gonadectomized animals manifested less severe untoward changes, survived in greater numbers, and experienced superior repair of their damaged hearts. Circulating levels of enzymes (e.g., CPK, GOT, GPT, and LDH), lipids, glucose, and BUN rose and fell during the acute necrosis and repair phases with distinct differences between the intact and castrated animals. Reciprocal changes in the weight of the adrenal and thymus glands, coupled with dynamic changes in circulating corticosterone levels, reflected marked temporal changes in the spectrum of adrenal steroids being secreted, as well as gonadal hormone mediated changes affecting adrenocortical function. The implications of these findings are that adrenocortical, androgenic, and estrogenic hormones condition the nature of the pathophysiologic response to acute myocardial infarction in rats.

Adrenal Glands↗

Early appearance of donor-type antigen-presenting cells in the thymuses of 1200 R radiation-induced bone marrow chimeras correlates with self-recognition of donor I region gene products.

The thymus exerts a potent influence on the development of I region self-recognition and antigen recognition by T cells. The mechanism by which the thymus acts on nascent T cells is unknown. It is assumed, however, that a cell interaction between the developing T cell and an la antigen-bearing cell in the thymus is involved. There are several candidates for the critical thymic cell; thymic epithelial, nurse, and antigen-presenting cells (APC) or dendritic cells. Because thymic epithelial cells derive from the third pharyngeal pouch and thymic APC derive from bone marrow, radiation-induced bone marrow chimeras allow the artificial creation of a chimeric thymus gland in which thymic epithelial cells and APC can be genetically different. We made radiation-induced bone marrow chimeras (F1 leads to P) using supralethal radiation doses (1200 R) and found bone marrow donor- (F1) type APC in the thymuses 3 wk after radiation. When such mice fully reconstitute their immune systems, their T cells behave as donor F1 phenotype T cells. Thus, the I region self-restriction and antigen-recognition repertoire of the T cells correlates with the genotype of the bone marrow-derived thymic APC, not the thymic epithelial cell.

Animals↗

Biological activities of Saccharomyces cerevisiae and fermented rice bran as feed additives.

AIMS: The objective of the present study was to examine for the various biological activities for feed additives of Saccharomyces cerevisiae and fermented rice bran. METHODS: The feed additives (100 g of each: YE, brewery yeast; PM, mixture of YE and SF; SF, fermented rice bran) were decocted with 2 l water at 100 degrees C to a half volume. RESULTS: The hot-water extract of PM was found to increase the stimulation of the macrophage activation (2.0-fold) and the intestinal immune modulating activity (1.8-fold), compared with those of control. When the hot-water extracts of PM, SF and YE were fed to the rats for 8 d (1 g kg-1 d-1), PM and SF showed the more effective anti-stress effect on spleen, thyroid and thymus gland. SIGNIFICANCE AND IMPACT OF THE STUDY: The hot-water extract of PM can have a significant impact on strengthening the living body's immune system and proliferating anti-stress activities with relation to enhance immunity.

Adrenal Cortex↗

Antigenic relationships in mammalian DNA polymerase.

Rabbit antibody was prepared against a high-molecular-weight DNA polymerase purified from the soluble fraction of calf thymus gland. This antibody does not inhibit terminal deoxynucleotidyl transferase isolated from that source, but does inhibit both low-molecular-weight and high-molecular-weight DNA polymerases isolated from cytoplasmic and nuclear fractions of a number of mammalian tissues (mouse L cells, calf thymus, phytohemagglutinin-stimulated human lymphocytes, rat liver, and rabbit bone marrow). The results suggest that (i) no antigenic relationship exists between terminal transferase and DNA polymerase, (ii) common antigenic determinants exist in the DNA polymerases from all mammalian sources, and (iii) multiple forms of DNA polymerase found in mammalian, cells are related by having polypeptide sequences or subunits in common.

Animals↗

Organotin-induced thymus atrophy concerns the OX-44+ immature thymocytes. Relation to the interaction between early thymocytes and thymic epithelial cells?

After single oral application of the organotin compound di-n-butyltindichloride (DBTC) to rats, a reversible dose-dependent thymus weight reduction is observed. This is maximal at day 4 and recovers to the control value approximately at day 9 after administration. In this study the changes in thymocyte subpopulations after a single oral dose of 15 mg DBTC/kg body weight were analysed by immunohistology. Thymus glands of exposed rats were collected at day 1,2,3,4,5,7 and 9 after DBTC dosing and frozen sections were screened for various thymocyte differentiation antigens. Staining by mAb HIS-44 that labels a subset of cortical thymocytes showed that the thymus atrophy was restricted to the cortex. Here a time-dependent decrease of labelling by CD2 (OX-34), CD8 (OX-8), CD4 (ER-2), and CD5 (OX-19) was observed. In contrast, the number of cortical OX-44+ cells increased from day 2 to day 5. This increase can reflect an increase of CD4-CD8- double-negative thymocytes or of macrophages. However, most of these OX-44+ cells were negative for acid phosphatase, which is present in most macrophages. We concluded that these OX-44+ cells were mainly CD4-CD8- thymocytes and that the thymocyte subpopulation of this phenotype, i.e. CD4-CD8-OX-44+, may be the target cell for DBTC. It is discussed whether DBTC might disturb the interaction of early thymocytes and thymic epithelium, probably by an interaction with the CD2 antigen.

Animals↗

Gas chromatographic analysis of free amino acids in the hyaloplasm of the hypophysis, pineal gland, thyroid gland, spinal cord, thymus and lymph nodes of the cow.

Studies of the qualitative and quantitative composition of free amino acids in the hyaloplasm of the hypophysis, pineal gland, thyroid gland, spinal cord, thymus and lymph nodes of the cow are described. The following findings are reported: the highest levels of alanine, valine, glycine, isoleucine, histidine, leucine, threonine, serine, phenylalanine, tyrosine and lysine are found in the thyroid gland, methionine and aspartic acid in the spinal cord, tryptophan and hydroxyproline in the pineal gland, and proline and glutamic acid in the thymus gland. The highest level by weight is that of glutamic acid in all tissues. The presence of alpha-aminobutyric acid combined with sarcosine and 4-aminoisobutyric acid with 2-AOA and citrulline with cystine was demonstrated. alpha-Aminoisobutyric acid and isovaline were found in the spinal cord.

Amino Acids↗

Identification of a novel parvalbumin in avian thymic tissue.

A novel calcium-binding protein has been isolated from chicken thymus tissue. Its molecular weight (approximately 11,500) and characteristic interactions with Tb3+ and Eu3+ identify the protein as a member of the parvalbumin family. Electrophoretically distinct from both chicken (muscle) parvalbumin and avian thymic hormone, it represents the third parvalbumin to be identified in avian tissues and the second to be identified in the avian thymus gland.

Animals↗

Acetylcholine receptor in rabbit thymus: antigenic similarity between acetylcholine receptors of muscle and thymus.

This study was performed to examine the presence and immunological properties of acetylcholine receptor (AChR) in rabbit thymus. Binding of 125I-alpha Bungarotoxin (alpha BGT) to Triton extract from rabbit thymus was saturable (half saturation value: 10 X 10(-9) M) and occurred with at least two affinities, a high one with a dissociation constant of 1.1 X 10(-10)M and a low affinity one with a dissociation constant of 2 X 10(-9)M. The complex formation of 125I-alpha BGT-thymus extract was inhibited by both carbamylcholine and D-tubocurarine. These results indicate the existence of AChR in rabbit thymus. Antibody to AChR which was purified from experimental myasthenic rabbits with Narke AChR-affinity gel and labelled with 125I was used to identify the receptor antigenicity in rabbit thymus. Specific binding of 125I-antibody to thymic extract was demonstrated by the DEAE-paper disc assay. It is concluded from these results that AChRs with a similar antigenicity to that of skeletal muscle AChR exist in rabbit thymus. Our findings obtained in this study will support a hypothesis that the primary immunogen in myasthenia gravis may be AChR in thymus and an autoimmune reaction against AChR might be initiated within the thymus gland itself.

Acetylcholine↗

Immunotoxicity of cupravit and previcur fungicides in mice.

Female mice received either cupravit or previcur at dose levels of 300 ppm and 1000 ppm, respectively, for 8 weeks. Humoral immune response was evaluated by measuring the plaque-forming cell (PFC) response and hemolysing antibody titers against sheep red blood cells (SRBCs), a T lymphocyte-dependent antigen. In addition, the hemagglutinating antibody titers against Escherichia coli lipopolysaccharide (LPS), a T cell-independent antigen, were determined. Both cupravit and previcur suppressed the PFC response by 74% and 78% of control values, respectively. The primary hemolysin antibody titers were reduced to 62% and 76% of control values, respectively. The hemagglutinating antibody titers were decreased to 66% and 77% of control values, respectively. Memory function was reduced as evidenced by inhibition of secondary hemolysin titers to SRBCs. Cell-mediated immunity was inhibited by both cupravit and previcur as evidenced by reduced delayed-type hypersensitivity (DTH) reaction to tuberculin to 77% and 76% of control values, respectively. Decreases in total leukocytic and lymphocytic counts were recorded together with histopathological changes in spleen and thymus gland of intoxicated animals.

Animals↗

Immunocompetence in relation to a heat-processed diet (Maillard reaction) in weanling rats.

Diets containing unheated casein (CD; control) or a casein-glucose mixture (CGD) previously heated at 140 degrees for 2 h were fed to two groups of young rats for 21 d. Differences in body weight, feed consumption, thymus, and spleen growth, protein metabolism and in vivo immune response were then determined. For this last experiment, animals were inoculated with sheep erythrocytes (SRBC) on day 15 to provide an immunological challenge. No changes were seen in body weight, feed consumption or feed conversion ratios. Neither were significant differences found in spleen weight, protein content, DNA content, DNase (EC 3.1.4.6) activity or lymphocyte count, suggesting that spleen cell growth remained similar in all the animals studied. The CGD induced marked increases in thymus DNA content whilst the protein:DNA ratio became lower. Spleen RNA content was similar in all rats, but thymus RNA content was 29% lower in the CGD group, although this difference did not reach statistical significance. This fact might be a consequence of the low RNase (EC 2.7.7.16) activity and RNase:RNA ratios in the thymus glands of CGD-fed animals. Further, the number of splenic plasma cells secreting anti-SRBC antibodies (direct plaque-forming cells) was significantly decreased in the same group. It might be concluded that both diets are adequate for rat growth and that the differences observed in the thymus of CGD-fed rats may be directed towards preserving tissue function. Nevertheless, the CGD did cause immunological disturbances affecting the humoral immune response.

Animal Nutritional Physiological Phenomena↗