Effect of testosterone on the kinetics of the development of suppressor cells in adjuvant arthritis

The induction of unresponsiveness to mycobacterial adjuvant took a longer time in male DA rats than in female rats. A shift in the induction time of unresponsiveness in males toward the female type was brought about by castration, but could be reverted to the male type by the application of testosterone. The transfer study revealed that cells capable of preventing arthritis required a longer incubation time for their development in males than in females. This suggests that testosterone inhibits the development of suppressor cells in adjuvant arthritis.     

Effect of testosterone on the kinetics of the development of suppressor cells in adjuvant arthritis

Summary The induction of unresponsiveness to mycobacterial adjuvant took a longer time in male DA rats than in female rats. A shift in the induction time of unresponsiveness in males toward the female type was brought about by castration, but could be reverted to the male type by the application of testosterone. The transfer study revealed that cells capable of preventing arthritis required a longer incubation time for their development in males than in females. This suggests that testosterone inhibits the development of suppressor cells in adjuvant arthritis.Acknowledgments. We are grateful to The Naito Foundation Research Grant for 1983.     

Effects of epinephrine on plasma fibrinogen levels in rats submitted to tissue injury

Summary Tissue injury (laparotomy) produces an increase in plasma fibrinogen. This increase is inhibited by the removal of the adrenal medulla, but injection of epinephrine in laparotomized-medullectomized rats returns fibrinogen levels to values similar to those observed in only laparotomized rats. Epinephrine administration to laparotomized rats increases the fibrinogen compared with the group of laparotomized rats without treatment, but epinephrine by itself does not modify plasma fibrinogen levels in uninjured rats. Epinephrine is apparently responsible for the increase of plasma fibrinogen in rats subjected to tissue injury, probably through beta adrenergic stimulation.     

Synergism between long-acting bromocryptine microcapsules and cyclosporine A in the prevention of various autoimmune diseases in rats

Pre-treatment of male Sprague-Dawley rats with long-acting bromocryptine microcapsules (CBLA) significantly inhibited the arthritic response to Freund's complete adjuvant and reduced weight loss, thymolysis, splenomegaly and leukocytosis. In the prevention of adjuvant arthritis (AA), the combination of CBLA plus sub-optimal doses of cyclosporine A (CsA) was more efficient than either of the drugs alone. Sub-optimal doses of CsA were 0.1 and 1.0 mg/kg/day s.c. for 5 days. Furthermore, CBLA alone did not decrease the incidence of experimental allergic uveitis (EAU) in the male Lewis rats. Low-dose CsA reduced the incidence of uveitis by 50%, and with the addition of CBLA, 100% of rats were protected. Low-dose CsA was 2 mg/kg/day i.m. for 14 days. Long-term treatment of male Sprague-Dawley rats with CBLA alone reduced the incidence and severity of spontaneous autoimmune periateritis nodosa (PN) in a dose-dependent manner; CsA was less potent than CBLA, and only additive effects were obtained. Finally, for the prevention of spontaneous autoimmune insulin-dependent diabetes (DM), the administration of CBLA did not improve the effect of a low-dose CsA in male BB rats. Nevertheless, a delay in onset of DM could be achieved. A sequential therapy using CsA plus CBLA clearly showed beneficial effects. The dose of CsA was 10 mg/kg p.o. 6 days/week for 21 weeks. Compared with Sprague-Dawley or Lewis male rats, BB male rats showed only weak prolactin suppression after the same doses of CBLA. It is suggested that the use of CBLA may be particularly beneficial in autoimmune disorders. The effectiveness of the combination therapy CBLA plus CsA, however, was dependent on the model considered. Various factors could play a role: (1) the different ways of administering CsA (s.c. in AA, i.m. in EAU and PN, oral in DM); (2) strain-dependency in the capacity of CBLA to suppress Prl secretion; and(3) at least in the BB rats, the transient increase of CsA bioavailibility which was possibly induced by CBLA.     

Hyperprolactinemia and estrogen-induced rhythms in LH and prolactin release in the ovariectomized rat

Short-term (9 days) hyperprolactinemia induced by pituitary grafts reduced basal plasma LH levels in ovariectomized rats whereas long-term (31 days) grafts increased basal LH levels. Although long-term grafts inhibited estradiol-induced prolactin surges, hyperprolactinemia had no effect on the LH surge. It is concluded that the estrogen-treated ovariectomized rat is not suitable for studying the effects of hyperprolactinemia on LH release.     

Roles for interleukin-2 (IL-2) and IL-4 in the generation of allocytotoxic T cells in the primary and secondary responses in vitro.

Roles for interleukin-2 (IL-2) and IL-4 in the generation of murine allocytotoxine T lymphocytes (allo-CTL) in the primary and secondary responses were studied in vitro. The generation of allo-CTL in the primary response was inhibited by anti-IL-2 monoclonal antibody (mAb), but was not inhibited by anti-IL-4 mAb. On the other hand, the generation of allo-CTL in the secondary response was partially inhibited by either anti-IL-2 or anti-IL-4 mAb, and it was almost completely inhibited by the combination of two mAbs. CD8+ cell-depleted splenocytes produced IL-2, but not IL-4, in response to alloantigens in the primary response, and these cells produced both IL-2 and IL-4 in the secondary response. Both exogenous IL-2 and IL-4 induced functionally active allo-CTL in the primary response from CD4+ cell-depleted splenocytes when these cells were stimulated with T cell-depleted allogeneic cells. These results suggest that the allo-CTL induction in the primary response is IL:-2-dependent and secondary allo-CTL induction is both IL-2 and IL-4-dependent, because unprimed CD4+ T cells produce IL-2, but not IL-4, whereas primed cells produce both IL-2 and IL-4 in response to alloantigens.     

Effect of an antiglucocorticoid (RU-38486) on hydrocortisone induction of maltase-glucosamylase, sucrase-isomaltase and trehalase in brush border membranes of suckling rats

Induction of alpha-glycosidases by hydrocortisone in suckling rats is inhibited by the daily administration of an antiglucocorticoid (RU-38486). Conversely, RU-38486 injected daily in 15-day-old rats for 7 days does not prevent the spontaneous development of alpha-glycosidases.     

Hyperprolactinemia and estrogen-induced rhythms in LH and prolactin release in the ovariectomized rat

Summary Short-term (9 days) hyperprolactinemia induced by pituitary grafts reduced basal plasma LH levels in ovariectomized rats whereas long-term (31 days) grafts increased basal LH levels. Although long-term grafts inhibited estradiol-induced prolactin surges, hyperprolactinemia had no effect on the LH surge. It is concluded that the estrogen-treated ovariectomized rat is not suitable for studying the effects of hyperprolactinemia on LH release.     

Enzymatic characteristics of the guanylate cyclase of KB cells: their change as a function of the development of the cultures]

We have localized 71% of the guanylate cyclase activity in the (G X 105,000) supernatent fraction of broken KB cells. The reaction follows Michaelis-Menten kinetics, the apparent Km for GTP is 0,5 mM, as long as GTP is lower than a limited concentration, then activity is inhibited. The ion Mn++ is an absolutely required activator, it does not change enzyme-substrate affinity. The enzyme shows several types of binding sites of Mn++. Guanylate cyclase, studied over a period of development of culture, shows, in KB cells without cell contact, an activity higher than that observed in confluent cells. This is not due to the fact of a change in enzyme-substrate affinity but to a modification of Mn++ influence.     

Inhibition of saline-induced diuresis in the rat by sulpiride

Summary Sulpiride (120 mg/kg, i.p.) inhibited saline-induced diuresis in the rat, an effect not observed with haloperidol, clozapine, pimozide or chlorpromazine. The antidiuretic effect of sulpiride also occurred in hypophysectomized rats suggesting that the response was not prolactin-mediated.     

Cellular and secreted tumor plasminogen activator: the effects of NaCl

Plasminogen activator, secreted by metastatic tumor cells, was strongly inhibited in buffer or tissue culture medium containing physiological concentrations of NaCl. Intact cells, however, expressed strong activity under similar conditions. Thus, if plasminogen activator is involved in invasion and metastasis, the cellular activity, acting as an ectoenzyme, may be more important than secreted enzyme under physiological conditions.     

Roles for interleukin-2 (IL-2) and IL-4 in the generation of allocytotoxic T cells in the primary and secondary responses in vitro

Roles for interleukin-2(IL-2) and IL-4 in the generation of murine allocytotoxine T lymphocytes (allo-CTL) in the primary and secondary responses were studied in vitro. The generation of allo-CTL in the primary response was inhibited by anti-IL-2 monoclonal antibody (mAb), but was not inhibited by anti-IL-4 mAb. On the other hand, the generation of allo-CTL in the secondary response was partially inhibited by either anti-IL-2 or anti-IL-4 mAb, and it was almost completely inhibited by the combination of two mAbs. CD8⁺ cell-depleted splenocytes produced IL-2, but not IL-4, in response to alloantigens in the primary response, and these cells produced both IL-2 and IL-4 in the secondary response. Both exogenous IL-2 and IL-4 induced functionally active allo-CTL in the primary response from CD4⁺ cell-depleted splenocytes when these cells were stimulated with T cell-depleted allogeneic cells. These results suggest that the allo-CTL induction in the primary response is IL:-2-dependent and secondary allo-CTL induction is both IL-2 and IL-4-dependent, because unprimed CD4⁺ T cells produce IL-2, but not IL-4, whereas primed cells produce both IL-2 and IL-4 in response to alloantigens.     

Inhibition of saline-induced diuresis in the rat by sulpiride.

Sulpiride (120 mg/kg, i.p.) inhibited saline-induced diuresis in the rat, an effect not observed with haloperidol, clozapine, pimozide or chloromazine. The antidiuretic effect of sulpiride also occurred in hypophysectomized rats suggesting that the response was not prolactin-mediated.     

Ultrastructural study of binucleation in cells of the rat adrenal glomerular zone after a prolonged low-sodium diet

Summary Binucleate cells have been found in the glomerular zone of the adrenal cortex in rats subjected to low-sodium diets. By considering the various possibilities for their production, both the findings of nuclei in process of constriction and nuclei identical in form, confronted and smaller in size than those of neighbour cells, are in agreement with an amitotic nuclear division as the possible mechanism for the formation of these cells.     

Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition

Summary Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that prostaglandin synthesis inhibition is primarily mediating the anti-inflammatory activity but prostaglandin synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited prostaglandin synthesis, inflammation and nociception in rats. The R-form had much less effect on prostaglandin synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics.     

Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition

Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that prostaglandin synthesis inhibition is primarily mediating the anti-inflammatory activity but prostaglandin synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited prostaglandin synthesis, inflammation and nociception in rats. The R-form had much less effect on prostaglandin synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics.     

Exocrine pancreatic enzymes in cycloheximide treated rats

Summary Cycloheximide, even in a dose of 0.25 mg/kg administered s.c. to rats stimulated by pancreozymin and secretin, inhibited lipase activity in pancreatic juice. Lipase activity in serum of control animals was inhibited by cycloheximide. The secretion of trypsin and chymotrypsin was also decreased.     

Evidence for no relationship of the pineal activity with the neonatal shrinkage of Leydig cells in the rat

Summary The collective volume of Leydig cells in prenatally pinealectomized newborn rats declined as sharply as in intact newborn rats. Also, the collective volume in pups born in the dark declined in a fashion similar to that in pups born in the light. The results indicate that neither the pineal gland nor the light is responsible for the neonatal shrinkage of Leydig cells.This study was supported in part by a Grant-in Aid for Scientific Research (No. 548067) from the Ministry of Education, Science and Culture of Japan.     

Inducing effect of clofibrate on alkaline phosphatase and histidine-glyoxylate aminotransferase in rat liver

Summary The activity of plasma membrane alkaline phosphatase and both mitochondrial and peroxisomal histidineglyoxylate aminotransferase was significantly increased in the livers of male rats following treatment with the hypolipidemic drug clofibrate. Cycloheximide or puromycin administration to rats inhibited the effects of clofibrate.     

Effects of isaxonine phosphate and analogs on fibroblast metabolism in culture

Human skin fibroblasts in confluent cultures were incubated for 24 h in the presence of isaxonine phosphate (Nerfactor) and several related factors. The incorporation of 14C-proline into secreted proteins and the release of collagen into the medium were inhibited. When the cells were incubated for an additional period of 24 h after thorough washing, protein and collagen syntheses were found to be identical to those of controls, demonstrating that the inhibition of protein synthesis was independent of any toxic effect. When cells were incubated in the presence of both isaxonine and colchicine, the secretion of collagen was more inhibited than by colchicine alone, and proteins accumulated in the cells.