Comparative studies on the effects of aminoglutethimide on hamster and rat adrenal cortex.

Adult female, intact or steroid suppressed hamsters were treated twice daily with 7 mg aminoglutethimide phosphate (AG) for 5 days while intact female rats received 14 mg AG per injection. AG resulted in an increase in adrenal gland weight of both hamster and rat. In the hamster AG had no effect on the amount of lipid droplets while in the rat a slightly higher number of fine lipid vacuoles was seen. In the hamster, enlargement of the gland was due to hyperplasia of the zona reticularis cells while in the rat the number of glomerulosa and fasciculata cells increased. AG had no effect on the adrenal cortex of steroid suppressed hamsters. The serum cortisol level was markedly higher in AG-treated hamsters while the corticosterone level was notably lower in AG-administered rats. In both hamsters and rats, AG-treatment did not change the serum ACTH level. Thus the study demonstrated different responses of the hamster and rat adrenal cortex to AG.     

Malignant disease of the lymphoid system in immunological perspective

The study of the structure of the lymphoid system has been an essential element in the overall progress of immunobiology. Study of the normal immune system, and especially study of immune deficiency disease, has revealed a remarkable degree of complexity within the lymphoid system, particularly at the cellular level. This complexity precludes the precise or definitive characterization of lymphoproliferative malignant disease by morphological criteria alone. However, new methodologies now available can be used to identify distinct lymphocyte subpopulations, each population possessing a characteristic set of markers or functions. As a result of these recent advances, the definition of lymphoproliferative malignant disease in immunological terms is entering a highly productive period.     

Effect on the immunological competence of Physalis pubescens L. in mice

Effect of different parts of the Physalis pubescens L. (Pp) on the immunocompetence were investigated in Kunming mice inbred lines. After 35 consecutive days of feeding, the mice were sacrificed to evaluate the immunologic function through the relative weights of spleen and thymus, the delayed type hypersensitivity (DTH), carbon particle clearance test and serum agglutination test. The results are summarised as follows: the pulp of Pp had statistically significant effect on the mice's non-specific immunity, but not on the weight of the mice's thymus. The Pp's pulp, peel and seeds had significant effect on the mice's cellular immunity, respectively, they had regulating effect on the mice's T-lymphocytes. Any part of Pp didn't have statistically significant effect on the mice's humoral immunity.     

The role of lymphoid cells in bone resorption: Cellular immunological competence in ia rats

The ia (incisors absent) rat is a naturally occurring mutant that has osteopetrosis resulting from reduced bone resorption. A number of in vestigators have reported that other osteopetrotic mutant rats (op) and mice (mi and op), in addition to demonstrating the skeletal manifestations of the disease, have cellular immunological defects. In light of the fact that bone resorption has been demonstrated to be controlled by hematopoietic tissues and more specifically by mononuclear cells isolated from lymphoid organs, it seemed appropriate to investigate immunological competence in the ia rat, to determine whether or not it had this defect in common with the op rat. Contrary to the results presented for other osteopetrotic mutants, we found that the thymuses in our ia mutants had a normal cellular composition and the T-cell-dependent zones in the lymph nodes were not deficient in lymphocytes. Therefore, this study was undertaken to investigate the response of ia rats to oxazolone, which produces one type of T-cell-dependent immune response, delayed hypersensitivity. The results of these studies indicate that ia rats at 18 days of age have the ability to develop delayed hypersensitivity, as shown by both a blastogenic response in the lymph node draining the site of sensitization and a positive skintest. The magnitudes of these responses were similar in ia and normal littermates, both histologically and quantitatively. Therefore, the ia mutant does not appear to have a defect of the thymus-dependent immune system, and further studies should be carried out to investigate other parameters of immunological competence in these animals.     

The interaction between macrophages and suppressor cells in immunological maturation in mice

The immunological immaturity at birth characteristic of species such as the mouse has no certain explanation. Here Bertie Argyris suggests that in mice it is a consequence of high suppressor-cell activity and an absence of macrophage activity. Gradual alterations in the balance of these activities account for the gradual emergence of immunocompetence.     

The effect of thymectomy and anti-thymocyte serum on the immunological competence of adult mice

The immune response of normal mice, adult thymectomized mice, micetreated with anti-thymocyte serum and ice which were treated with antithymocyte serum (ATS) after hymectomy were studied for their response to tobacco mosaic virus (TMV) as antigen, 52, 84 and 316 days after the beginning of treatment. Adult mice, treated after thymectomy with ATS, failed to produce detectable antibodies to TMV. The role of the thymus in the adult mouse in the immune response to a thymus-dependent antigen is discussed.     

Melatonin and the adrenal cortex: relationship to territorial aggression in mice

The behaviour of male TO mice on confrontation after a period of group housing (3 mice/group) was recorded, both in terms of group and individual aggression measures. A series of treatments was carried out aimed at identifying the relative contributions of corticosteroids (CS) and melatonin (MEL) to control of fighting. Adrenalectomy (ADX) and aminoglutethimide injections (AMG) were used to reduce CS both chronically and acutely, and repeated restraint stress (RES) to increase CS levels chronically. MEL was administered daily (5 days), alone or in combination with other treatments. Control group treatments included sham operation for ADX (SO), and the appropriate saline injections. Untreated groups were also tested. AMG and ADX reduced aggression to a similar extent on all measures. MEL potentiated fighting, but this effect was reversed when given in combination with ADX or AMG. RES was associated with a significant shift towards submission on individual measures, but no significant change in group measures. RES+MEL treatment did not cause any significant changes. SO animals behaved normally, but again, the aggressogenic MEL effect was not seen after SO + MEL. The results are interpreted in terms of partial inhibition of CS output by MEL.     

Relationship between the adrenal cortex and thymic involution in “lethargic” mutant mice

To determine if the adrenal gland plays a role in the thymic involution which occurs spontaneously in “lethargic” mutant mice, three different studies were made. Morphological studies were made first to determine if there was an indication of histological changes in the adrenal glands. Next, serum levels of corticosterone were measured by radioimmunoassay. Finally, mice were unilaterally adrenalectomized to see if such treatment would improve various symptoms of “lethargic” mutants. Results of the studies showed that lipid granules in the cortical cells of “lethargic” mutants were greatly reduced in number during the time of spontaneous thymic involution, and the mutant mice had a significantly higher level of serum corticosterone than the normal controls. Mutant mice unilaterally adrenalectomized at 15 days of age showed a marked improvement in their condition and their mortality rate decreased. It is concluded that spontaneous thymic involution of “lethargic” mutants is probably associated with adrenocortical hypersecretion.     

Role of thyroid hormones in the maturation and organisation of rat barrel cortex.

The influence of thyroid hormones on cortical development was analysed in rat somatosensory cortex. Maternal and foetal hypothyroidism was induced and maintained by methimazole treatment from embryonic day 13 onwards. 5-Bromo-2'-deoxyuridine (BrdU) labelling in hypothyroid rats showed that cell positioning during corticogenesis followed an inside-out pattern. The radial neurogenetic gradients were more diffuse at all ages with respect to normal rats due to the inappropriate location of many cells, including those of the subcortical white matter. Most (62%) of the cells in the subcortical white matter of hypothyroid rats were labelled at embryonic day 15. Nissl staining of the primary somatosensory cortex showed blurred cortical layer boundaries and an abnormal barrel cytoarchitecture. Cytochrome oxidase and peanut agglutinin staining showed that the tangential organisation of the posteromedial barrel subfield and its layer IV specificity was not lost in hypothyroid rats. However the temporal pattern of peanut agglutinin labelling was delayed 3-4 days with respect to normal rats. In hypothyroid rats, the total barrelfield tangential area was reduced by 27% with respect to normal. The total tangential barrel area, corresponding to peanut agglutinin-negative labelling, occupied 77% of the barrelfield area and only 66% in hypothyroid rats. This reduction was larger with cytochrome oxidase staining where the total barrel area occupied 69% of the barrelfield area in normal and 46% in hypothyroid rats.Our data stress the importance of maternal and foetal thyroid hormones during development, and demonstrate the irreversible effects that maternal and foetal hypothyroidism may have on the intrinsic organisation and maturation of the neocortex.     

Betamethasone effects on fetal sheep cerebral blood flow are not dependent on maturation of cerebrovascular system and pituitary–adrenal axis

Synthetic glucocorticoids are administered to pregnant women in premature labour to accelerate fetal lung maturation at a time when fetal cerebrovascular and endocrine systems are maturing. Exposure to glucocorticoids at 0.8–0.9 of gestation increases peripheral and cerebrovascular resistance (CVR) in fetal sheep. We examined whether the increase of CVR and its adverse effect on cerebral blood flow (CBF) depend on the current level of maturation of the pituitary–adrenal axis and the cerebrovascular system. Using fluorescent microspheres, regional CBF was measured in 11 brain regions before and 24 h and 48 h after the start of 3.3 μg kg⁻¹ h⁻¹ betamethasone ( n = 8) or vehicle ( n = 7) infusions to fetal sheep at 0.73 of gestation. Hypercapnic challenges were performed before and 24 h after the onset of betamethasone exposure to examine betamethasone effects on cerebrovascular reactivity. Betamethasone exposure decreased CBF by approximately 40% in all brain regions after 24 h of infusion ( P < 0.05). The decline in CBF was mediated by a CVR increase of 111 ± 16% in the cerebral cortex and 129 ± 29% in subcortical regions ( P < 0.05). Hypercapnic cerebral vasodilatation and associated increase in CBF were blunted ( P < 0.05). Fetal CBF recovered after 48 h of betamethasone administration. There were no differences in glucocorticoid induced CBF and CVR changes compared with our previous findings at 0.87 of gestation. We conclude that the cerebrovascular effects of antenatal glucocorticoids are independent of cerebrovascular maturation and preparturient increase in activity of the fetal pituitary–adrenal axis.     

Assessment of neuronal maturation and acquisition of functional competence in the developing zebrafish olfactory system

Olfactory coding at the level of the olfactory bulb is thought to depend upon an ensemble response of mitral cells receiving input from chemotopically-organized projections of olfactory sensory neurons and regulated by lateral inhibitory circuits. Immunocytochemical methods are described to metabolically classify neurons in the developing zebrafish olfactory system based on the relative concentrations of taurine, glutamate, GABA (and potentially other small biogenic amines) and a small guanidium-based cation, agmatine, which labels NMDA-sensitive cells by permeating through active ionotropic glutamate receptor channels. Using metabolic profiling in conjunction with activity dependent labeling we demonstrate that neuronal differentiation in the developing olfactory bulb, as assessed by acquisition of a mature neurochemical profile, and sensitivity to an ionotropic glutamate receptor agonist, NMDA, occurs during the second day of development. This experimental approach is likely to be useful in studies concerned with the development of glutamatergic signaling pathways.     

The effects of hyperglycemia on adrenal cortex function and steroidogenesis in the zebrafish

Since the 1950s, scientists have attempted to characterize the relationship between diabetes mellitus (DM) and the hypothalamic-pituitary-adrenal (HPA) axis. Similar complications are seen in patients with diabetes and Cushing's syndrome, leading some to suggest that an underlying abnormality in the HPA axis may be responsible among those with DM. By inducing hyperglycemia in a zebrafish animal model, we show a direct correlation between glucose and cortisol levels.     

Retention and egg production ofMicrophallus pygmaeus in mice: the influence of the adrenal cortex

Fewer adultMicrophallus pygmaeus are recovered from the small intestine of adrenalectomized male mice than from sham-operated counterparts. Preinfection intraperitoneal injection of 2 IU or 4 IU ACTH adaily for 7 days increases the initial primary worm burden in male mice. Preinfection intramuscular injection of 325 g corticosterone daily for 7 days increases the initial worm burden and alters the subsequent rate of decline and duration of the primary infection. However, egg production is unaffected. The changes in parasite numbers are attributed to the immunosuppressive action of corticosterone.