Several prostaglandins inhibit the cAMP response to glucagon and P-adrenergic stimulation in hepatocytes. To probe the mechanism of this inhibition, we have examined in primary hepatocyte cultures how pretreatment with pertussis toxin (islet-activating protein) influences the ability of the cells to respond to hormones and prostaglandins. Pertussis toxin augmented the effects of glucagon, epinephrine and isoproterenol, and also markedly enhanced the cAMP response to prostaglandin El (PGE1). Furthermore, whereas PGE1, PGE,, PGIz and PGF,, attenuated the cAMP responses to glucagon in control cultures, this inhibition was abolished in cells pretreated with pertussis toxin. A more detailed comparison was made of the effects of PGEl and PGF,,. In cells not treated with pertussis toxin, both these prostaglandins at high concentrations reduced the cAMP response to glucagon and isoproterenol by approximately 50%, but dose-effect curves showed that PGEl was about 100-fold more potent as an inhibitor than PGFza. Pertussis toxin abolished the inhibitory effects of PGEl and PGF,, with almost identical time and dose requirements. The results obtained with PGEI, PGE2, PGI, and PGF,, suggest that prostaglandins of different series attenuate hormone-activable adenylate cyclase in hepatocytes through a common mechanism, dependent on the inhibitory GTP-binding protein.The formation of cAMP is subject to both positive and negative control. This regulation appears to be exerted through GTP-binding proteins (G proteins) that transduce stimulatory and inhibitory signals from the receptors to the catalytic moiety of the adenylate cyclase [l -51. In the case of inhibitory regulation, the understanding of the mechanisms involved has been facilitated by the observation [6] that receptor-mediated decreases in cAMP could be abolished by treating cells with pertussis toxin (islet-activating protein) [7, 81, which was subsequently found [9, 101 to act by ADPribosylating the CI subunit of an inhibitory G protein (Gi).Prostaglandins may both stimulate and inhibit the formation of CAMP [ll - cAMP accumulation by E prostaglandins is prevented by pertussis toxin in fat cells [32], mammary tumor cells [33] and kidney [34], suggesting a role of the Gi. It is not known whether different prostaglandins inhibit the cAMP system by a common mechanism. It is also unknown if the inhibitory and stimulatory effects of prostaglandins on the adenylate cyclase are mediated via the same receptors.In the liver, prostaglandins of the E series stimulate the adenylate cyclase only slightly [35 -371. However, many prostaglandins, including those of the E and F series, markedly inhibit the response to glucagon or epinephrine [19 -22, 38, 391. The purpose of the present study was to investigate the mechanisms behind the prostaglandin-induced attenuation of hormonal responsiveness and the role of the Gi protein in the regulation of cAMP in liver cells. We have used cultured hepatocytes, and examined the effect of pertussis toxin on cAMP responses to hormones and vari...

Three infants developed severe hemolytic anemia following the second or third diphtheria-pertussistetanus vaccination. Direct antiglobulin tests were positive, and the infant most severely affected also had reduced serum complement levels, indicating an immunological mechanism for the hemolysis. The presence of IgM on the erythrocytes from 2 of the infants could be demonstrated by antiglobulin tests or immunization experiments. Heat eluates of the erythrocytes from one of the infants contained antibodies to tetanus and diphtheria toxoids, as well as to Bordetella pertussis, suggesting that these antibodies were antigenically bound to the erythrocytes. Virus antibodies or isoagglutinins, present in the serum, were not found in the eluate. No antibodies against the vaccine components could be demonstrated in eluates of erythrocytes from control subjects. In vivo experiments showed that tetanus and diphtheria toxoids were easily bound to human erythrocytes. This finding could help explain the pathogenesis of the autohemolysis.

During a period of 2 1/2 years 190 children have been prophylactically treated with zoster immunoglobulin in norway. Information on 130 (68%) of these children was obtained. This group included patients suffering from leukemia, lymphoma, and other malignant disorders, and patients with autoimmune diseases, with impaired immune mechanisms or with for other reasons increased frequency of infections, as well as premature and weak newborns, and infants born to mothers who developed varicella during the last 4 days before delivery. Of the patients who received zoster immunoglobulin within 3 days after exposure, 2.9% developed weak symptoms of varicella. When zoster immunoglobulin was administered 4-5 days after exposure, 37.5% contracted varicella, and when given more than 5 days after exposure, 50% developed the disease. The 9 neonates with possible intrauterine exposure are not included in these figures.

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