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The thymus. Pediatric surgical aspects.

Since the original description of thymic death in an infant 400 years ago, the thymus has been recognized as an important structure to practitioners caring for infants and children. The source of many cysts, masses, and tumors in the neck and mediastinum, the thymus gland merits the pediatric surgeon's attention. The thymus is clearly an important lymphoid organ, the removal of which may be therapeutic in MG, but congenital absence leads to profound cell-mediated immunodeficiency. The immunologic sequelae of its neonatal extirpation remains obscure. It is apparent that further research is needed to clarify the functional role of the thymus gland in the developing immune system. Until better elucidated, a conservative approach to neonatal thymectomy may be justified.

Child↗

Multiple types of receptors for atrial natriuretic peptide.

The binding of atrial natriuretic peptide (ANP) to olfactory bulb, pituitary anterior lobe and thymus gland membranes was examined. [125I]ANP (rat, 99-126) bound specifically to the three types of membranes. However, the affinity for ANP receptor in olfactory bulb was much higher than those in either pituitary or thymus gland. Competitive inhibition of cold ANP (rat, 99-126) with [125I]ANP binding sites on olfactory bulb membranes gave a value of 796 +/- 80 pM (mean +/- S.E.M., n = 4) as a dissociation constant (Kd) of cold ANP (rat, 99-126), while on pituitary and thymus membranes, the competitive curve gave a value of 9.3 +/- 0.4 nM (mean +/- S.E.M., n = 3) and 25.5 +/- 2.2 nM (mean +/- S.E.M., n = 6) as a Kd of cold ANP (rat, 99-126), respectively. Furthermore, a truncated ANP fragment (rat, 111-126) did not inhibit the [125I]ANP binding in olfactory bulb, while this peptide fragment inhibited the [125I]ANP binding in either pituitary or thymus gland with affinities only 2- to 4-fold less potent than ANP (rat, 99-126). These data indicate the possibility of the existence of multiple types of ANP receptors. We propose alpha-receptor in olfactory bulb and beta-receptor in either pituitary anterior lobe or thymus gland.

Animals↗

Carcinogenesis and aging. IV. Effect of low-molecular-weight factors of thymus, pineal gland and anterior hypothalamus on immunity, tumor incidence and life span of C3H/Sn mice.

The low-molecular-weight polypeptide factors were obtained from bovine thymus (TF), pineal gland (PF) and anterior hypothalamus (AHF). Both TF and PF administration enhanced the rejection of skin allograft and stimulated the immunological response to sheep erythrocytes in adult CBA mice. Treatment of CBA mice with AHF increased the graft survival and inhibited antibody formation to sheep erythrocytes. Chronic TF or PF administration decreased spontaneous tumor development and prolonged the life span of female C3H/Sn mice. Administration of AHF failed to influence the life span and the tumor incidence of female C3H/Sn mice. The role of immunity and hormonometabolic shifts in mechanisms of both aging and the age-associated increase in cancer incidence are discussed.

Aging↗

Evidence that I-E-negative mice resistant to neonatal H-2 tolerance induction display ubiquitous thymic clonal deletion of donor-reactive T cells.

Induction of neonatal H-2 tolerance is highly efficient in most allodisparate strain combinations, with the exception of those in which neonatal recipients do not, but donor cells do, express I-E molecules. For example, less than 25% of I-E-nonexpressing B10.S mice become tolerant following neonatal injection with I-E+ (B10.AxB10.S)F1 cells. It has been hypothesized that the high rate of nontolerance observed in I-E-nonexpressing neonatal recipients of injections of I-E-bearing cells is caused by a failure to delete V beta 11+ cells in the immediate postnatal period. To test this possibility, we have examined V beta 11 expression and tolerogen-responsiveness among T cells of thymus and spleens harvested periodically from B10.S mice after neonatal inoculation of (B10.AxB10.S) F1 cells. We found that V beta 11+ cells were selectively eliminated within 1-2 days from the thymus glands of all recipient mice, B10.A-specific proliferative T cells disappeared concordantly, and the thymus glands contained donor-derived chimeric cells. Subsequently, an increasing proportion of injected mice acquired V beta 11+ thymocytes and B10.A-responsive T cells, while losing chimeric cells. However, deletion and in vitro nonreactivity were still apparent in the majority of mice at 60 days of age. We conclude that neonatal inoculation of I-E-expressing cells established thymic chimerism and caused profound elimination of V beta 11+ cells from the thymus glands of all injected mice. Therefore, the failure of the majority of neonatally injected B10.S mice to display transplantation tolerance of B10.A antigens as adults cannot be ascribed to an inability to delete I-E-reactive thymocytes.

Animals↗

Hox group 3 paralogs regulate the development and migration of the thymus, thyroid, and parathyroid glands.

The thymus, thyroid, and parathyroid glands in vertebrates develop from the pharyngeal region, with contributions both from pharyngeal endoderm and from neural crest cells in the pharyngeal arches. Hoxa3 mutant homozygotes have defects in the development of all three organs. Roles for the Hoxa3 paralogs, Hoxb3 and Hoxd3, were investigated by examining various mutant combinations. The thyroid defects seen in Hoxa3 single mutants are exacerbated in double mutants with either of its paralogs, although none of the double-mutant combinations resulted in thyroid agenesis. The results indicate that the primary role of these genes in thyroid development is their effect on the development and migration of the ultimobranchial bodies, which contribute the parafollicular or C-cells to the thyroid. Hoxb3, Hoxd3 double mutants show no obvious defects in the thymus or parathyroids. However, the removal of one functional copy of Hoxa3 from the Hoxb3, Hoxd3 double mutants (Hoxa3 +/-, Hoxb3-/-, Hoxd3-/-) results in the failure of the thymus and parathyroid glands to migrate to their normal positions in the throat. Very little is known about the molecular mechanisms used to mediate the movement of tissues during development. These results indicate that Hoxa3, Hoxb3, and Hoxd3 have highly overlapping functions in mediating the migration of pharyngeal organ primordia. In addition, Hoxa3 has a unique function with respect to its paralogs in thymus, parathyroid, and thyroid development. This unique function may be conferred by the expression of Hoxa3, but not Hoxb3 nor Hoxd3, in the pharyngeal pouch endoderm.

Animals↗

[Incorporation of 14-c-1-glycine into tissue proteins under the influence of insulin and its derivatives].

Effect of parenterally injected insulin and its composite sulpho-A- and B-chains on the rate of protein synthesis by the organs of the rat was investigated. It has been shown that insulin accelerates the incorporation of I-C14-glycine into proteins of the liver, kidneys, pancreas, spleen, sceletal muscules, thyroid gland, thymus and adrenal glands but does not influence this process in the cardiac muscle and diaphragm. A- and B-chains also activated protein metabolism in some organs, but despite some specificity of their action its extent was more limited as compared to that of insulin.

Adrenal Glands↗

Peptides of pineal gland and thymus prolong human life.

OBJECTIVES AND DESIGN: Researchers of the St. Petersburg Institute of Bioregulation and Gerontology of the North-Western Branch of the Russian Academy of Medical Sciences and the Institute of Gerontology of the Ukrainian Academy of Medical Sciences (Kiev) clinically assessed the geroprotective effects of thymic (Thymalin) and pineal (Epithalamin) peptide bioregulators in 266 elderly and older persons during 6-8 years. The bioregulators were applied for the first 2-3 years of observation. RESULTS: The obtained results convincingly showed the ability of the bioregulators to normalize the basic functions of the human organism, i.e. to improve the indices of cardiovascular, endocrine, immune and nervous systems, homeostasis and metabolism. Homeostasis restoration was accompanied by a 2.0-2.4-fold decrease in acute respiratory disease incidence, reduced incidence of the clinical manifestations of ischemic heart disease, hypertension disease, deforming osteoarthrosis and osteoporosis as compared to the control. Such a significant improvement in the health state of the peptide-treated patients correlated with decreased mortality rate during observation: 2.0-2.1-fold in the Thymalin-treated group; 1.6-1.8-fold in the Epithalamin-treated group; 2.5-fold in the patients treated with Thymalin plus Epithalamin as compared to the control. A separate group of patients was treated with Thymalin in combination with Epithalamin annually for 6 years and their mortality rate decreased 4.1 times as compared to the control. CONCLUSIONS: The obtained data confirmed the high geroprotective efficacy of Thymalin and Epithalamin and the expediency of their application in medicine and social care for health maintenance and age-related pathology prevention in persons over 60 to prolong their active longevity.

Aged↗

Relationship of emotional behaviors induced by electrical stimulation of the hypothalamus to changes in EKG, heart, stomach, adrenal glands, and thymus.

The relationships of hypothalamically elicited emotional behaviors to their accompanying pathophysiological effects were examined as a model of how complex "emotional behaviors" may be related to fundamental psychosomatic disorders. Twenty-two unanesthetized adult cats were studied. EKG alterations and histological changes in the heart, stomach, adrenal glands, and thymus were related to the specific stereotypical emotional behaviors that could be elicited by hypothalamic stimulation in tamed subjects. Restlessness, threat, and searching-biting behaviors were evoked by electrical stimulation of the anteromedial, ventromedial, and lateral hypothalamus, respectively. The occurrence of cardiac arrhythmias, ST and/or T (ST-T) changes in the EKG, histological damage to myocardium, gastric erosion, and adrenal hyperplasia were generally observed in the restlessness and threat groups but not in the searching-biting group. The pathophysiological effects were similar in the restlessness and threat groups with no specific EKG change or organ effect attributable to either site of stimulation. Hypothalamically elicited restlessness or threat behaviors in cats are each associated with cardiac, gastric, and adrenal pathophysiologies.

Adrenal Glands↗

Antidepressants reverse the olfactory bulbectomy-induced decreases in splenic peripheral-type benzodiazepine receptors in rats.

The present study investigated the effects of 21-day administration of clorgyline (1 mg/kg/day), desipramine (10 mg/kg/day) or paroxetine (10 mg/kg/day) on peripheral-type benzodiazepine receptors in rat peripheral tissues following bilateral olfactory bulbectomy. Thymus and spleen weights decreased as a result of bulbectomy. Subsequent antidepressant drug administration had no further effects on the weights of thymus glands but increased those of spleens. In thymus glands, higher densities of peripheral-type benzodiazepine receptors were observed in medulla than in cortex; no significant variations were observed following bulbectomy or antidepressant drug administration. In spleen, higher densities were observed in white pulp than in red pulp. The bulbectomy-induced decreases in binding densities observed in both regions were reversed following administration of antidepressants. Adrenal peripheral-type benzodiazepine receptors were not altered by bulbectomy or subsequent treatment with clorgyline or desipramine while paroxetine upregulated these receptors. No changes in kidney peripheral-type benzodiazepine receptors were observed. The present study confirms that cell lines of the rat immune system possess high densities of peripheral-type benzodiazepine receptor binding sites and further support the contention that, following olfactory bulbectomy, rats may present an antidepressant-reversible immunitary dysfunction.

Animals↗

GH3 pituitary adenoma cells can reverse thymic aging in rats.

Thymic size and T-cell function decrease with age, and it has not yet been possible to totally reverse this thymic atrophy and completely restore T-cell-dependent immune functions. In this study, GH3 pituitary adenoma cells, which secrete growth hormone and prolactin, were implanted subcutaneously into 16- and 22-month-old female Wistar-Furth rats and the rats were sacrificed approximately 2 months later. Only thymic remnants were detected in aged, non-implanted rats, but thymus glands were found in both the 18- and the 24-month-old rats that had been implanted with GH3 cells. Thymus glands from the GH3-implanted 18-month-old rats contained distinct cortical thymocytes and medullary epithelial cells. Depending on the concentration of phytohemagglutinin or concanavalin A, T-cell proliferative responses of splenocytes from these implanted rats were 2- to 5-fold greater than those of 18-month-old controls. At the optimal concentration of mitogen, proliferative responses to either lectin could be restored to those levels observed in splenocytes from 3-month-old Wistar-Furth females. Thymus glands from 24-month-old GH3-implanted rats contained more cortical thymocytes and fewer fat vacuoles than controls, but they were not totally reconstituted. No significant lectin-induced T-cell proliferative responses or IL-2 secretion were detected in 24-month-old control rats, but splenocytes from GH3-implanted rats showed augmented T-cell proliferative responses and increased synthesis of IL-2. Fluorescence-activated cell-sorter analysis of thymocytes revealed that 24-month-old rats implanted with GH3 cells had a higher proportion of lymphocytes with the Thy-1.1 and helper-T-cell phenotypes. These data show that it is possible to regenerate normal thymic tissue in situ and reverse the natural loss in cell-mediated immunity that occurs with aging.

Adenoma↗

[Comparison of pharmacological studies on ootheca Mantidis].

The pharmacological effects of three species of Ootheca Mantidises were compared. The results indicate that Tenodera sinensis can increase the index of testis and thymus gland, and has an antidiuretic effect in mice; Statilia maculate can prolong the swimming time and ordinary pressing anoxia, increase the index of spleen and thymus gland, raise the temperature in mice, decrease the content of LPO in liver of the hypercholesteremia rats, and has an antidiuretic effect; Hierodula patellifera can increase the index of testis and thymus gland, raise the temperature in mice, and decrease the content of LPO in liver of the hypercholesteremia rets. The LD50 of the three species of Ootheca Mantidises are all over 320 g/kg.

Animals↗

Closed mediastinal exploration in patients with persistent hyperparathyroidism.

Described are two patients with persistent hyperparathyroidism after unsuccessful neck explorations. Both had deep mediastinal parathyroid tumors located within the thymus gland. Formerly it had been the practice of the authors to perform a median sternotomy for the removal of such tumors. In the present cases, however, the neck was re-explored through a cervical incision and the entire thymus gland then was removed by the technique of "closed mediastinal thymectomy." An enlarged parathyroid gland was found embedded in the resected parenchyma of the thymus gland in each patient, and both were cured by the operation.

Adolescent↗