M Viganò

Antigen- and mitogen-stimulated cytokine production by peripheral blood mononuclear cells (PBMC) of 50 pregnant women and 31 age- and sex-matched non-pregnant controls were analysed to determine whether changes in cytokine production occur during normal and pathologic human gestation. The pregnant women, consecutively enrolled during a 3-month period, were undergoing a normal, non-pathologic pregnancy at the time of entry into the study, and underwent ultrasound examination to ascertain the exact week of pregnancy and the vitality of the fetus. Forty of the 50 pregnancies (80%) terminated physiologically with the birth of normal babies. Spontaneous abortions were observed in 5/50 (10%) women, and five women gave birth to newborns small for gestational age (SGA). A decrease in the production of IL-2 and interferon-gamma (IFN-gamma) accompanied by an increase in production of IL-4 and IL-10, was observed in normal pregnancy, with the lowest quantities of IL-2 and IFN-gamma and the highest quantities of IL-4 and IL-10 present in the third trimester of pregnancy. Statistically significant increased production of both IL-2 and IFN-gamma and reduced production of IL-10 characterized pathologic pregnancies and distinguished them from normal pregnancies. These preliminary data suggest that a type 2 cytokine profile may be associated with normal human pregnancy, whereas the lack of a dominant type 2 cytokine profile may be indicative of a pathologic pregnancy.

BACKGROUND: Metabolic diseases are frequently observed in HIV-infected persons and, as the risk of contracting these diseases is age-related, their prevalence will increase in the future as a consequence of the benefits of antiretroviral therapy (ART). SUMMARY OF GUIDELINES: All HIV-infected persons should be screened at regular intervals for a history of metabolic disease, dyslipidaemia, diabetes mellitus, hypertension and alteration of body composition; cardiovascular risk and renal function should also be assessed. Efforts to prevent cardiovascular disease will vary in intensity depending on an individual's absolute risk of ischaemic heart disease and should be comprehensive in nature. Lifestyle interventions should focus on counselling to stop smoking, modify diet and take regular exercise. A healthy diet, exercise and maintaining normal body weight tend to reduce dyslipidaemia; if not effective, a change of ART should be considered, followed by use of lipid-lowering medication in high-risk patients. A pre-emptive switch from thymidine analogues is recommended to reduce the risk of development or progression of lipoatrophy. Intra-abdominal fat accumulation is best managed by exercise and diet. Prevention and management of type 2 diabetes mellitus and hypertension follow guidelines used in the general population. When using medical interventions to prevent and/or treat metabolic disease(s), impairment of the efficacy of ART should be avoided by considering the possibility of pharmacokinetic interactions and compromised adherence. Specialists in HIV and specialists in metabolic diseases should consult each other, in particular in difficult-to-treat cases. CONCLUSION: Multiple and relatively simple approaches exist to prevent metabolic diseases in HIV-infected persons; priority should be given to patients at high risk of contracting these diseases.

Cell-mediated immunity and T-lymphocyte maturation are impaired in HIV-infected children. These abnormalities would be detected in HIV-uninfected offspring of HIV women (seroreverters [SR]) if HIV or its soluble proteins could cross the placental barrier. Immunophenotypic analyses were performed in 20 healthy HIV-uninfected newborns of HIV-infected mothers (SR), and in 14 healthy newborns of HIV-negative women (UC). The same analyses were performed in 3 groups of older children: SR (n = 41); UC (n = 15); and HIV-infected children (n = 25). Antigen-specific cells were evaluated with ELISpot and fluorimetric analyses; IL-7 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that in SR newborns: (1) the CD4/CD8 ratio was reduced, (2) CD4(+) and CD8(+) naive T-cell percentages were decreased, (3) percentage of activated CD8(+) T cells was increased, and (4) percentages of CD3(+)/4(-)/8(-) (DN) and DN/25(-)/44(+) were augmented. These abnormalities were partially retained in older SR children. CD4(+) and CD8(+) HIV-specific cells were detected in a portion of newborn SRs but not in older SRs. Serum IL-7 was augmented both in newborn and older SRs. Cell-mediated immunity and T-cell maturation are altered even in HIV-uninfected newborns of HIV-infected mothers; these abnormalities persist over time. The biologic significance of these observations and potential subsequent clinical events should be investigated in larger cohorts of seroreverters. (Blood. 2000;96:3866-3871)

We have examined the post-translational processing of G alpha subunits expressed endogenously in rat PC12 and NG108-15 rat/mouse hybrid cells, and after transfection of cDNA expression constructs into COS cells. Thioester-linked palmitoylation of alpha o, alpha s, alpha q/alpha 11 and alpha 12 has been detected by metabolic labelling with [3H]palmitate and immunoprecipitation. Palmitoylation of alpha o occurs post-translationally in cells treated with protein-synthesis inhibitors, suggesting possible dynamic acylation. Palmitoylation of the C-terminal CAAX motif has been excluded. Site-directed mutagenesis of alpha o has been used to implicate the site of modification as a cysteine residue next to the N-terminal myristoylated glycine, in a novel protein-lipid modification motif Met-Gly-Cys. The non-palmitoylated alpha o mutant is still myristoylated but shows reduced membrane binding, suggesting that reversible palmitoylation may regulate G alpha localization and function.