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Pregnancy-related involution of the thymus in the viviparous lizard, Chalcides ocellatus.

The thymus gland of the adult viviparous lizard, Chalcides ocellatus (Reptilia, Sauria, Scincidae) undergoes conspicuous morphological changes in relation to gestational period. During pregnancy, the thymus is depleted of thymocytes and undergoes changes coming to consist primarily of numerous degenerative cysts. Thymic involution occurs early during pregnancy (starting at phase II) and reaching its highest level at parturition (phase V). These observations correlate with the circulating level of blood progesterone, measured by radioimmunoassay, and suggest a possible relationship between thymic involution and the activity of sex hormones.

Animals↗

[Morphological aspects of inopportune fatty metamorphosis of the thymus].

Thymus glands from 43 early infants who died of asphyxia, birth injury and inflammatory diseases were studied morphologically. Unscheduled fatty metamorphosis (UFM) of the thymus was found in 32% of cases of inflammatory diseases. Lipid containing cells of the thymus are thymic macrophages in the state of irreversible lipoid dystrophy and death. Macrophagal enzymopathy with the disturbance of intracellular lipid digestion may account for it. Lipid dystrophy is also noted in some epithelial cells. It is shown that the accumulation of the lipids in thymic macrophages occurs not only in unscheduled fatty metamorphosis, but also during the accidental transformation of the thymus, thus the latter may be considered as a physiologic analogue of UFM. In case of UFM, however, this process acquires a pathologic character and results in macrophage death. Therefore, UFM may be considered as a variant of the accidental transformation abnormality of the thymus.

Fat Necrosis↗

Transplantation of fetal liver tissue suspension into the spleens of adult syngenic rats: inducibility of cytochrome P450 dependent monooxygenase functions by beta-naphthoflavone, phenobarbital and dexamethasone.

In the present study the effects of beta-naphthoflavone (BNF), phenobarbital (PB) and dexamethasone (DEX) on cytochrome P450 (P450) dependent monooxygenase functions were investigated in intrasplenic liver cell explants in comparison to adult liver. Fetal liver tissue suspensions were transplanted into the spleens of 60-90 days old adult male syngenic Fisher 344 inbred rats. 2, 4 or 6 months after surgery, transplant recipients and age matched controls were orally treated with BNF (1x50 mg/kg body weight (b.wt.)), PB (1x50 mg/kg b.wt.), DEX (for 3 days 4 mg/kg b.wt. per day), or the respective solvents (dimethylsulfoxide or 0.9% NaCl). The animals were sacrificed 24 (BNF, DEX) or 48 (PB) hours after the last treatment. P450 mediated monooxygenase functions were measured in spleen and liver 9000 g supernatants by three model reactions for different P450 subtypes: ethoxyresorufin O-deethylation (EROD; 1A), ethoxycoumarin O-deethylation (ECOD; 1A, 2A, 2B), and ethylmorphine N-demethylation (END; 3A). Spleen weights were significantly higher in transplanted rats, compared to controls, at all three time points after surgery. Induction with PB or DEX, and in some cases also with BNF, lead to a significant increase in liver weights of transplant recipients and control rats independent of the time after transplantation. In contrast, there was no influence on spleen weights due to BNF or PB. At all time points after surgery, with DEX a marked decrease in body weights, weights of adrenal glands and of lymphatic organs like thymus glands and spleens was observed, with the weights of the transplant containing spleens being still higher in comparison to control organs. Spleens of control animals displayed nearly no P450 mediated monooxygenase functions neither without nor with induction. After transplantation, however, significant EROD and ECOD, but hardly any END activities were seen in the host organs at all three time points after surgery. In transplant containing spleens EROD and ECOD were significantly increased after BNF or PB treatment at all three time points after surgery, and ECOD after DEX administration, but at 4 and 6 months after transplantation only. END was only induced after DEX treatment at 6 months after transplantation. With the livers of both transplant recipients and control rats EROD and ECOD were increased after BNF induction and EROD, ECOD, and END after PB treatment at all three time points after transplantation. After DEX administration END was significantly enhanced only at 2 and 4 months after transplantation, ECOD was decreased at 2 and 4 months, and EROD was diminished at all three time points after surgery. Transplantation of fetal liver tissue suspensions into the spleens did not influence monooxygenase functions and their inducibility within the respective livers of the animals. These results demonstrate that transplanted liver cells originating from syngenic fetal liver tissue suspensions display P450 dependent monooxygenase functions which are, simi lar to normal adult liver, inducible by BNF, PB and DEX. Both monooxygenase functions and their inducibility within the transplant containing spleens display quantitative and qualitative developmental changes.

Animals↗

Immunofluorescence studies of disseminated Hantaan virus infection of suckling mice.

Hantaan virus, the etiological agent of Korean hemorrhagic fever, was inoculated intracerebrally or intraperitoneally into suckling mice, and the course of the infection was followed by infectivity titration and immunofluorescence studies. Mice became ill and were moribund by 13 to 14 days postinfection. In mice inoculated either intracerebrally or intraperitoneally, virus antigen was present in brain, heart, lungs, liver, and kidney. Less consistently, specific fluorescence was observed in spleen, pituitary gland, thymus, lymph nodes, adrenal, pancreas, salivary glands, trigeminal ganglia, adipose tissue, intestine, and muscle. In all of these tissues, the primary target of infection was the capillary endothelium. In mice inoculated intracerebrally, virus antigen was present mainly in choroid plexus, hippocampal nuclei, and meninges, but in mice inoculated intraperitoneally, central nervous system infection was marked by antigen accumulation in cortical nuclei and thalamus.

Animals↗

[Structural and immunomorphological characteristics of the human thymus in embryogenesis].

The thymus glands from one hundred of 4--34-week-old human fetuses were studied by the histologic, histochemical, immunomorphologic and electron microscopic methods. The development of the organ is described from the standpoint of systemogenesis. The laying of the gland is defined at the 5th week of the fetus development, and it reflects the features of the epithelium of the head intestine organs. The differentiation of the reticuloepithelium, the population of the gland by lymphocytes and emergence of antigenic specificity on their surface state at the age of 7--8 weeks. The growth zone of the thymus reticuloepithelium, the significance of Hassal's bodies, the appearance and quantitative dynamics of two subpopulations of T-lymphocytes are described. From 11--12 till 34 weeks of fetal development the percentage of T-lymphocytes forming rosettes with sheep red blood cells virtually does not change (70--90%), while the percentage of lymphocytes forming rosettes with their own red cell increases during the same period from 23 to 70%.

Gestational Age↗

Transplantation of cultured thymus fragments. III. Induction of allotolerance.

Balb/c nude mice were transplanted with cultured thymic fragments from C57BL/6, hybrid (C57BL/6xC3H F1 or BALB/cxC3H F1) or 2 separate strains simultaneously. Tolerance to H-2 of the thymus donor strain(s) was assessed by skin-graft acceptance and was seen in all cases except where 2 thymuses, each of differing strains, were transplanted simultaneously. Examination of mixed leukocyte culture and cell mediated lympholysis revealed blunted reactivity against thymus donor strains when skin graft tolerance was seen. Demonstration of a suppressor cell population was unsuccessful although a decreased cytotoxic T-cell potential was suggested by decreased GVH activity. These studies showed a unique dependence upon the thymus gland for the phenomenon demonstrated and are taken to be an example of a more generalized process in which effector cell function of the thymus is controlled by intrathymic events during the early maturation of precursor effector cells.

Animals↗

[Features of therapy of hematologic diseases in old age. 3. Features in the occurrence and clinical course of aplastic and neoplastic diseases of the blood].

The development and course of blood diseases in the aged often are determined by two factors: The first is the disturbance of the immune system based on a defective interaction between the T- and B-cell system. These are due to the involution of the thymus gland accompanied by reduced incretion of thymus hormones. The second factor consists in a regressive alteration of a "haemopoietic inductive micro-environment (Trentin), which has its morphological substrate in the circulatory system and the stroma of the bone marrow. Both factors lead to atrophic or diminished recovery of the bone marrow. Specific therapeutic problems are presented on the basis of several selected disease entities. Anaemias, cytopenias, the myeloproliferative syndrome and the lymphomas of low malignancy as well as the paraproteinaemias reveal the importance of the above-mentioned factors not only for the pathogenesis and the course but also for the treatment of these conditions in old age.

Age Factors↗

Toxic interactions between copper sulphate and some organic agrochemicals.

Groups of rats were treated with graded doses of zineb or aldicarb solely or in association with copper sulphate for nine consecutive weeks. Body weight gain was retarded and thymus gland weight was decreased in all treated groups. A pronounced synergism between copper sulphate and zineb was noticed in lowering the weights of thymus, testes, and adrenal glands. Various degrees of reduction in hemoglobin concentration, red blood cells and platelet counts occurred after treatment with the above-mentioned agrochemical regimen. Copper sulphate synergised the elevation of serum alkaline phosphatase (AP) activity, and bilirubin concentration as well the reduction of hemoglobin concentration by zineb. Alanine aminotransferase (ALT) activity was significantly increased, while cholinesterase (ChE) activity was decreased in all treated groups. Serum triglycerides (TGs) were lowered in rats treated with medium or high doses of zineb or aldicarb.

Adrenal Glands↗

Rat thymic dihydrotestosterone receptor: preparation, location and physiochemical properties.

Castration in the male rat has been shown to produce enlargement of the thymus gland while treatment with dihydrotestosterone (DHT) results in a decrease in thymic size in these animals. To determine if these changes might be receptor mediated, thymus tissue from castrate male rats was removed and homogenized in buffer and centrifuged to produce cytosol. By Scatchard plot analysis, it was shown that a specific DHT receptor was present at a concentration of 0.24 +/- 0.02 pmoles/g tissue and it possessed a KA of 2.51 +/- 0.45 x 10(9)M-1. This thymic DHT receptor sedimented on 5--20% sucrose gradients in the 8s region. By competition analysis it was found that testosterone only partially competed (25%) for this receptor, with virtually no binding noted for estradiol, progesterone, and cortisol. The receptor was found to be localized in the reticuloepithelial matrix of the thymus and was not present in the thymic lymphocyte fraction.

Animals↗

Acute thymic involution in fetuses and neonates with chorioamnionitis.

Chorioamnionitis represents the leading cause of preterm birth and related pathologic conditions as well as of fetal death and frequently occurs in symptom-free mothers. Recent radiologic findings have indicated that thymus size is significantly reduced in preterm infants born to mothers with subclinical, histologically proven chorioamnionitis. However, an accurate morphologic description of the thymus gland in fetuses and neonates with chorioamnionitis is lacking, although it is known that infection and other stress processes may cause lymphocyte depletion in the thymuses of infants and older babies (acute stress involution). We describe morphologic modifications in the thymus of fetuses with histologically proven chorioamnionitis and newborn infants with chorioamnionitis and proven sepsis. The main findings included (1) decreased organ volume (ANOVA, P < .0024); (2) reduced corticomedullary ratio (P < 10(-6)); (3) significant changes in the relationship between thymic parenchyma and thymic interstitial tissue with resulting increased organ complexity (P = .03); (4) severe reduction of thymocytes; and (5) other degenerative processes such as monocyte/macrophage infiltration of Hassall's bodies. These results indicate that chorioamnionitis, with or without sepsis, is associated with significant morphologic modifications in the thymus. We wish to note that the described thymic pathology is only one aspect of the fetal systemic inflammatory response syndrome with which chorioamnionitis is associated.

Abortion, Spontaneous↗

Chronic dietary copper deficiency alters biochemical and morphological properties of mouse lymphoid tissues.

Chronic copper deficiency in mice impairs both humoral and cell-mediated immunity, but the mechanisms are unknown. Copper deficiency was produced in C58 mice by feeding dams a diet low in copper throughout lactation and weaning the pups to this diet. Control mice were from dams fed the same diet but with copper supplementation the drinking water. Six-week-old mice were sampled for biochemical and morphological studies. Compared to copper-supplemented mice, copper-deficient animals were smaller, anemic and exhibited hypoceruloplasminemia. The copper-deficient mice have small thymus glands, enlarged spleens, and livers equivalent in size to copper-supplemented mice. Thymic atrophy is not caused by elevated serum corticosterone. Liver, spleen, and thymus tissues from copper-deficient mice exhibit low cytochrome oxidase (56, 38, and 45%, respectively) and superoxide dismutase activities (61, 60, and 43%, respectively) compared to tissues from copper-supplemented mice, indicating a functional copper deficiency. Electron micrographs taken of thymus and spleen from copper-deficient mice demonstrate altered morphology characterized by abnormal mitochondria and misshapen nuclei. Chronic copper deficiency alters the size, biochemistry and morphology of primary (thymus) and secondary (spleen) lymphoid tissue.

Animals↗

Thymic cysts in the neck.

The etiologic considerations in head and neck lesions rarely include the diagnosis of thymic cysts. A correlative summary of three new cases was analyzed with respect to the already existing body of data. A classification of thymic cysts, their embryogenesis, clinical signs, and appropriate pre-operative studies were stressed. The gross and microscopic histopathology was reviewed with the conclusion that in many instances normal thymus was included in the surgical specimen. Given our increasing knowledge regarding thymic function, it was stressed that heightened awareness of this clinical entity should enable preservation of the normal thymus gland.

Child↗

Anti-rabbit thymus actin antibody inhibits proliferation of Epstein-Barr virus-transformed human B cell line LA350: augmentation by cyclic AMP.

Antibody to actin isolated from the rabbit thymus gland exerted a dose-dependent inhibitory effect upon the proliferation of an Epstein-Barr virus-transformed human B cell line, LA350. Purified rabbit thymus actin specifically reversed the inhibitory effect of antibody by competing with surface actin on LA350. For example, LA350 proliferation at 48 hr was inhibited 90% at a 1:10 antibody dilution (p less than 0.001) but only 48% and 20% in the presence of 190 and 380 micrograms/ml of rabbit thymus actin, respectively (p less than 0.001 for reversal). Cyclic AMP augmented in a dose-related fashion the inhibitory effects of antibody, e.g., a 1:20 dilution of antibody inhibited 10, 19, 41, and 67% at 0.0, 0.5, 1.0, and 2.0 mM cAMP, respectively (p less than 0.001). We conclude that anti-actin antibody recognizes surface actin on a human B cell line and produces a functional inhibition of proliferation by a process that is augmented by cAMP.

Actins↗

Reversal reaction in patients with lepromatous leprosy after transplantation of human fetal thymic grafts.

An attempt has been made to reconstitute impaired cell-mediated immunity in 1 patient with indeterminate, 4 patients with borderline and 2 patients with polar lepromatous leprosy by grafting three thymus glands obtained from human fetuses of 14--19 weeks gestation. Most of these patients had severe ulcerative erythema nodosum leprosum (ENL) and were intolerant to dapsone. After thymus transplantation these patients were followed for 1 1/2 years. During this period, all conventional chemotherapy had been withdrawn. In most cases, there was dramatic improvement of the clinical condition, resolution of skin lesions, subsidence of ENL, clearance of bacteria from skin and reconstitution of several immunologic deficits; but late lepromin reactivity returned in none, which indicated permanent lose of resistance to Mycobacterium leprae.

Adult↗

Chronobiological features of the immune system. Effect of calorie restriction.

The circadian organization of living organisms is fully established being a key component the activity of the neuro-endocrin-immune system that maintains the homeostasis. Secondary lymph organs, such as submaxillary lymph nodes and spleen, have been shown to exhibit a 24 h variation in blastogenic proliferative capacity and distribution of B and T subsets, with specific achrophases depending on the parameter studied or the lymphoid organ considered. However, less is known about the thymus. The immune system has been shown to change by calorie restriction, although no information is available about possible effects in 24 h variations. Similar questions can be posed for the neuro-endocrine system. As an example, some data are shown in this article about the effects of calorie restriction on the neuro-endocrin-immune system in growing male Wistar rats. Calorie restriction blunted the circadian secretory pattern of TSH observed in the control group that was characterized by the existence of two peaks at 17:00 or 01:00 h and that explained the low basal metabolic rate of these animals under this experimental condition. Concerning the immune system, the thymus gland exhibited 24 h variations in T, B and immature cells in both control and calorie-restricted male rats, thus confirming the circadian organization of the immune system. Moreover this circadian organization was changed by calorie restriction.

Animals↗

Proteolytic degradation of calf thymus terminal deoxynucleotidyl transferase.

A high molecular weight preparation of terminal transferase containing 58,000- and 44,000-dalton peptides has been purified from calf thymus glands. The relationship of these terminal transferase peptides to the low molecular weight form was established with an immunoblot procedure using rabbit antibody directed against the homogeneous calf thymus low molecular weight terminal transferase (32,000 daltons). The 58,000- and 44,000-dalton enzyme species are each shown to be enzymatically active by renaturation in situ after electrophoresis on polyacrylamide gel in the presence of sodium dodecyl sulfate. These results suggest that the homogeneous terminal transferase previously described is derived from the higher molecular weight species by proteolysis during fractionation. Controlled degradation of the high molecular weight calf thymus terminal transferase with trypsin produces fully active enzyme containing alpha- and beta-peptides similar to those found in the 32,000-dalton species. Isoelectric focusing experiments show a decrease of isoelectric pH of the enzyme with proteolysis.

Animals↗