Epinephrine-induced elevation of guanosine 3′:5′-cyclic monophosphate in isolated fat cells of rat

The effects of epinephrine (as low as 0.1 muM) on guanosine 3':5'-cyclic monophosphate (cGMP) and adenosine 3':5'-cyclic monophosphate (cAMP) in isolated fat cells were examined. Epinephrine increased both cGMP and cAMP levels, with the elevation of cAMP preceding the rise of cGMP. Maximal elevation was obtained with 1 muM epinephrine for each nucleotide. The increase in content of cGMP and cAMP due to epinephrine was completely blocked by a beta-adrenergic antagonist (5 muM propranolol). Phentolamine (10-100 muM), an alpha-adrenergic antagonist, enhanced the response to epinephrine resulting in elevation of cAMP levels, whereas a high concentration (100 muM) of phentolamine suppressed the elevation of cGMP. The ability of epinephrine to increase cGMP and cAMP levels was markedly diminished by "feedback regulator" partially purified from the incubation mixtures of isolated fat cells exposed to epinephrine [Ho, R.J. & Sutherland, E. W. (1971) J. Biol. Chem. 246, 6822-6827], whereas an increase in cGMP, but not cAMP, levels was observed in isolated fat cells incubated with "feedback regulator" alone (without epinephrine). These observations suggest the possibility that the epinephrine-induced elevation of cGMP levels in isolated fat cells might be mediated by an increase in formation of intracellular "feedback regulator" due to an elevation of cAMP by epinephrine.     

Enhancement of cytotoxicity of NK cells by D-Fraction, a polysaccharide from Grifola frondosa

In innate immunity, activated natural killer (NK) cells attack and damage pathogens such as bacteria and virus without restriction by the MHC antigen. NK cells activated by IL-12 have been reported to recognize and kill tumor cells in perforin-mediated apoptosis. We have reported that D-Fraction, a polysaccharide extracted from the maitake mushroom (Grifola frondosa), activates macrophages, dendritic cells, and T cells and inhibits the growth of tumor cells. However, the effects of D-Fraction on NK cell function in the innate immune response are not well known. In the present study, we administered D-Fraction to MM-46 mammary tumor-bearing C3H/HeJ mice intraperitoneally for 3 consecutive days and investigated its effects on the activation and cytotoxicity of NK cells. D-Fraction significantly enhanced the cytotoxicity against NK-sensitive YAC-1 cells and the expression of CD223 on NK cells. D-Fraction also increased the expression of CD86 on macrophages. In addition, the levels of IL-12 in the culture supernatant of whole spleen cells and in serum increased, compared with the control corresponding to an increase in expression of IL-12 receptor betaI on NK cells. These results suggest that D-Fraction enhances the cytotoxicity of NK cells through the production of IL-12 by macrophages activated by D-Fraction.     

Relapsing polychondritis studied by computed tomography

Computed tomographic findings in a patient with relapsing polychondritis are described. Collapse of the cartilage of the nose and calcification in cartilages of the ears were clearly demonstrated. CT scanning was also helpful in evaluating the tracheobronchial tree for airway compromise, which could prove fatal in this condition.