Overnight dexamethasone suppression test: normal responses and the diagnosis of Cushing's syndrome

Serum cortisol levels were measured the morning after the administration of 1 mg of dexamethasone. Only 5 of 190 subjects had serum cortisol levels greater than 2 micrograms/dL. Thus, the normal value after dexamethasone suppression is less than 2 micrograms/dL rather than less than 5 micrograms/dL as has generally been accepted. The distinction is important because some individuals with Cushing's syndrome partially suppress their cortisol levels to less than 5 but more than 2 micrograms/dL during the test procedure. Thus, the use of 5 micrograms/dL as the normal value may lead to an unnecessary delay in diagnosis.     

Dominant lethal studies in male mice after exposure to 2.45 GHz microwave radiation

Adult male mice had the lower halves of their bodies exposed in a waveguide system to 2.45 GHz microwave radiation for 30 min. The half body dose-rate of 43 W kg-1 had been shown in a previous study [7] to deplete severely the heat-sensitive stages of sperm production. The males were mated at intervals to adult hybrid females over the following 8-10 weeks. There was no significant reduction in post-implantation survival, suggesting that the microwave exposure did not have a mutagenic effect on the male germ cells. However, pregnancy rate was significantly reduced in weeks 3, 4, 5 and 6; reaching a minimum of about 10% of the control value in weeks 4 and 5. The occurrence of low values in weeks 4 and 5 correlated well with the expected reductions in sperm count due to the pattern of depletion of the spermatogenic epithelium of the testes. Thus it was concluded that the reduced pregnancy rate resulted from reduced male fertility. Pre-implantation survival can also be affected by reduced sperm count [8] and was significantly reduced in this study but it correlated less well with the anticipated heat response. A further study is in progress looking at the contribution of sperm count and sperm abnormality to the results.     

Estrogen accelerates immune complex glomerulonephritis but ameliorates T cell-mediated vasculitis and sialadenitis in autoimmune MRL lpr/lpr mice.

Estrogen is known to influence immune responses in healthy subjects in a dichotomous fashion. Thus, in number of previous studies we and others have demonstrated that B cell activities are augmented after exposure to estrogen whereas T cell reactivity is suppressed. Furthermore, it has been shown that this hormone has significant impact on the course of certain human and experimental autoimmune diseases. In this study we report that treatment with physiological doses of estradiol exerts dichotomous effects on different manifestations of the lupus disease in MRL/l mice. On one hand immune complex-mediated glomerulonephritis was significantly accelerated. This outcome was due to polyclonal B cell activation with increased production of antibodies to double-stranded DNA and formation of circulating immune complexes. In contrast, T cell-mediated lesions such as focal sialadenitis, renal vasculitis, and periarticular inflammation were all significantly ameliorated in MRL/l mice exposed to estrogen. Thus, we were able to demonstrate that, within one subject and even within one organ, administration of estrogen leads to differential outcome of SLE morbidity. We propose that the differential effect of estrogen on the manifestations of the autoimmune disease of MRL/l mice is due to its dichotomous effects on B and T cell-mediated immune responses.     

Location and dynamics of alpha-tocopherol in model phospholipid membranes with different charges.

Studies were made on the position and dynamics of the OH-group of alpha-tocopherol in phospholipid membranes. There was no difference in the spin-lattice (T1) relaxation times at the 5a-position of alpha-tocopherol labeled with 13C- or C19F3-determined from the nuclear magnetic resonance (NMR) spectra of liposomes positively charged with stearylamine (SA) and negatively charged with dicetylphosphate (DCP). The zeta-potentials of egg yolk phosphatidylcholine (EYPC) liposomes with and without SA or DCP were not affected by incorporation of 20 mol% alpha-tocopherol, though incorporation of 10 mol% ascorbyl-palmitate decreased the zeta-potentials of EYPC and EYPC-SA liposomes. The P==O stretching band (1235 cm-1) of the phosphate group and C==O stretching band (1734 cm-1) of the acyl ester linkage in dimyristoylphosphatidylcholine (DMPC) liposomes, measured by Fourier transform-infrared (FT-IR) spectroscopy, were not changed by incorporation of alpha-tocopherol. These results suggest that no specific interaction occurred between the OH-group of alpha-tocopherol and the polar interfacial region of the bilayer. The dynamic quenching effects of n-(N-oxy-4,4'-dimethyloxazolidine-2-yl)stearic acids (n-NSs) on the intrinsic fluorescence of alpha-tocopherol were in the order 5-NS > 7-NS = 12-NS > 16-NS. Acrylamide, a water-soluble fluorescence quencher with a very low capacity to penetrate through phospholipid bilayers, had very low quenching efficiency. These results indicate that the bulk of the chromanol moiety of alpha-tocopherol is located in a position close to that occupied by the nitroxide group of 5-NS in the membranes and is poorly exposed at the membrane surface.(ABSTRACT TRUNCATED AT 250 WORDS)