This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function. 相似文献
Because both metabolic (Met Acid) and respiratory acidosis (Resp Acid) have diverse effects on mineral metabolism, it has been difficult to establish whether acidosis directly affects parathyroid hormone (PTH) secretion. Our goal was to determine whether acute Met Acid and Resp Acid directly affected PTH secretion. Three groups of dogs were studied: control, acute Met Acid induced by HCl infusion, and acute Resp Acid induced by hypoventilation. EDTA was infused to prevent acidosis-induced increases in ionized calcium, but more EDTA was needed in Met Acid than in Resp Acid. The PTH response to EDTA-induced hypocalcemia was evaluated also. Magnesium needed to be infused in groups receiving EDTA to prevent hypomagnesemia. The half-life of intact PTH (iPTH) was determined during hypocalcemia when PTH was measured after parathyroidectomy. During normocalcemia, PTH values were greater (p < 0.05) in Met Acid (92 +/- 19 pg/ml) and Resp Acid (77 +/- 22 pg/ml) than in controls (27 +/- 5 pg/ml); the respective pH values were 7.23 +/- 0.01, 7.24 +/- 0.01, and 7.39 +/- 0.02. The maximal PTH response to hypocalcemia was greater (p < 0.05) in Met Acid (443 +/- 54 pg/ml) than in Resp Acid (267 +/- 37 pg/ml) and controls (262 +/- 48 pg/ml). The half-life of PTH was greater (p < 0.05) in Met Acid than in controls, but the PTH secretion rate also was greater (p < 0.05) in Met Acid than in the other two groups. In conclusion, (1) both acute Met Acid and Resp Acid increase PTH secretion when the ionized calcium concentration is normal; (2) acute Met Acid may increase the bone efflux of calcium more than Resp Acid; (3) acute Met Acid acts as a secretogogue for PTH secretion because it enhances the maximal PTH response to hypocalcemia. 相似文献
Background: Mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels play a pivotal role in mediating cardiac preconditioning. The effects of intravenous anesthetics on this protective channel have not been investigated so far, but would be of importance with respect to experimental as well as clinical medicine.
Methods: Live cell microscopy was used to visualize and measure autofluorescence of flavoproteins, a direct reporter of mitoKATP channel activity, in response to the direct and highly selective mitoKATP channel opener diazoxide, or to diazoxide following exposure to various anesthetics commonly used in experimental and clinical medicine. A cellular model of ischemia with subsequent hypoosmolar trypan blue staining served to substantiate the effects of the anesthetics on mitoKATP channels with respect to myocyte viability.
Results: Diazoxide-induced mitoKATP channel opening was significantly inhibited by the anesthetics R-ketamine, and the barbiturates thiopental and pentobarbital. Conversely, urethane, 2,2,2-trichloroethanol (main metabolite of [alpha]-chloralose and chloral hydrate), and the opioid fentanyl potentiated the channel-opening effect of diazoxide, which was abrogated by coadministration of chelerythrine, a specific protein kinase C inhibitor. S-ketamine, propofol, xylazine, midazolam, and etomidate did not affect mitoKATP channel activity. The significance of these modulatory effects of the anesthetics on mitoKATP channel activity was substantiated in a cellular model of simulated ischemia, where diazoxide-induced cell protection was mitigated by R-ketamine and the barbiturates, while urethane, 2,2,2-trichloroethanol, and fentanyl potentiated myocyte protection. 相似文献
Delayed graft function (DGF) in cadaver kidney transplants is a common problem and is often due to acute tubular necrosis (ATN). DGF in transplants may have a deleterious effect on long-term graft survival. Since thyroid hormone has been shown to hasten recovery from ATN in experimental models, we designed a trial to determine if a defined course of triiodothyronine (T3) would improve the short- or long-term outcome of patients with DGF in cadaveric transplants. A prospective, randomized, placebo controlled, double blind trial of T3 was carried out in patients with DGF in cadaveric renal transplants. End-points were percentage requiring dialysis, percentage recovering function, time to recovery and length of hospital stay. Long-term outcomes were percentage grafts functioning at 1 year and mean serum creatinine at 1 year. Forty-four patients were randomized to receive either T3 or placebo. Three patients were dropped from each group when early biopsies disclosed that DGF was due to rejection. The groups were well matched by age, cold ischemia time of the graft, and percentage reactivity to a random panel of antigens. Baseline thyroid function studies, including T3, reverse T3 (rT3), and thyroid stimulating hormone (TSH) levels, were similar between the two groups and typical of 'euthyroid-sick syndrome'. T3 had no effect on percentage requiring dialysis, time to recovery, percentage recovering function, or length of stay. At 1 year follow-up, graft function was similar in both groups and significantly lower than that seen in patients with good initial function. Thyroid hormone, given early in the course of DGF in cadaver kidney recipients, had no effect on the course of DGF. Long-term graft function is impaired in patients who experience post-transplant DGF compared to those who have good initial function. 相似文献