Unique microRNA Signals in Plasma Exosomes from Pregnancies Complicated by Preeclampsia.

Although preeclampsia is a common and serious complication of pregnancy, insight into its pathobiology and diagnosis is lacking. Circulating plasma exosomes, which contain RNA and other molecules and have recently become accessible for diagnostics, may be informative in this regard. We tested the hypothesis that preeclampsia may affect the miRNA cargo within circulating maternal blood exosomes. We collected plasma from 60 pregnant women at term, including 20 women with pregnancy complicated by preeclampsia, and 20 women with fetal growth restriction and 20 with healthy pregnancy, serving as controls. We isolated exosomes from the maternal plasma by continuous density gradient ultracentrifugation. Our main outcome variable was exosomal miRNA cargo, analyzed by quantitative polymerase chain reaction-based TaqMan advanced miRNA assay in a card format and the expression of differentially expressed exosomal miRNA in whole plasma from the same participants. We found that 7 miRNA species were differentially expressed in exosomes from women with preeclampsia and those from controls. In contrast, there was no significant difference in exosomal miRNA expression between women with fetal growth restriction and controls. The results were not affected by fetal sex. Only one of the preeclampsia-related, differentially expressed exosomal miRNAs was significantly different in whole plasma miRNA analysis. We concluded that unlike whole plasma miRNA, exosomes extracted from the plasma of women with preeclampsia exhibit a unique miRNA profile, suggesting that plasma exosomal miRNA could provide insight into the pathophysiology of preeclampsia, and may play a role in disease diagnostics.

A hospital-based prospective study of perinatal infection with human immunodeficiency virus type 1.

Most infants with pediatric acquired immunodeficiency syndrome and infections with human immunodeficiency virus type 1 (HIV-1) are infected perinatally by their mothers. To determine the proportion of exposed infants who are infected, we conducted a hospital-based prospective study in HIV-1-infected women whose infants were delivered at a single metropolitan hospital in Miami, Fla. A population of uninfected women and their infants was also enrolled and followed longitudinally for 2 years to assess laboratory and clinical measurements. The median follow-up is now 18 months for 82 infants born to HIV-1-infected mothers. The proportion of infected infants in this group is 0.30 (25/82). None of the infants born to 110 HIV-1-seronegative mothers were seropositive. Infected infants were easily distinguished from noninfected infants by virus isolation. No single immunologic or hematologic measure was predictive of infection for all infants at risk for HIV-1 infection who were 6 months of age or younger. As a group, however, infected infants could be distinguished from uninfected index infants by a number of immunologic measures by 6 months of age; the absolute number of CD4+ lymphocytes and the CD4+/CD8+ lymphocyte ratio were the variables most predictive of infection. As in retrospective studies, clinical disease developed in 80% of infected infants within the first 24 months of life. This study provides documentation of HIV-1 perinatal transmission risk and early correlates of infection in young infants from a single hospital.

Safety and tolerance of intermittent intravenous and oral zidovudine therapy in human immunodeficiency virus-infected pediatric patients. Pediatric Zidovudine Phase I Study Group.

Thirty-five children with symptomatic human immunodeficiency virus infection were enrolled in a 12-week, three-center phase I study of intravenous and oral zidovudine therapy. At enrollment the children ranged in age from 5 months to 13 years, with a median age of 3 1/2 years. Twenty-one children (60%) had acquired immunodeficiency syndrome and 14 (40%) had the related complex; 20 children had less than 0.5 10(9) CD4+ lymphocytes per liter (less than 500 cells/mm3) at entry. Zidovudine was administered in one of three escalating dose regimens. One or two months of intravenous treatment with zidovudine every 6 hours was followed by orally administered drug on the same schedule; zidovudine was infused at 80, 120, or 160 mg/m2/dose, and the oral dose was one and one-half times the intravenous dosage. Adverse events were similar to those observed in adults. Neutropenia (absolute neutrophil count less than 0.75 10(9)/L (750 cells/mm3] occurred in nine patients. The median neutrophil count fell from 2.50 10(9)/L at entry to 1.72 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven patients; the median hemoglobin level among nontransfused patients decreased from an entry value of 108 to 105 gm/L (10.8 to 10.5 gm/dl). Dosage adjustments were made in 15 patients, in 12 because of anemia or neutropenia. No patients required permanent discontinuation of zidovudine because of toxic effects. Positive effects included a faster-than-anticipated rate of weight gain, decreased hepatosplenomegaly, and lowering of the total IgG and IgM concentrations toward more normal values. Zidovudine appears to be safe and to have manageable toxic effects in children.

Epidemiologic background of blood donors with antibody to human T-cell lymphotropic virus. Transfusion Safety Study Group.

We interviewed 51 blood donors in four major US metropolitan areas subsequently found to have had antibodies to human T-cell lymphotropic virus (anti-HTLV) in late 1984-early 1985. Sixteen donors (31%) reported that they or a sexual contact had a history of blood transfusion. Twelve donors (24%) reported that they or a sexual contact used intravenous drugs. Ten donors (20%) were blacks born in the southeastern US. Four of the male donors (15%) reported homosexual contact. The most common characteristic was an association with Japan or the Caribbean basin (61%). These results show a broader variation of epidemiologic backgrounds than anticipated.

Acquired immunodeficiency syndrome in infants.

Fourteen infants with clinical and laboratory features of an acquired immunodeficiency syndrome were identified in a single metropolitan area from November 1980 to July 1983. Patients were predominantly of Haitian parentage, although two cases occurred in offspring of non-Haitian intravenous drug abusers. Only one patient had received a blood transfusion before the development of clinical findings. The predominant clinical findings included failure to thrive, persistent infection of the oral mucosa by Candida albicans, chronic pulmonary infiltrates, hepatosplenomegaly, lymphadenopathy, and diarrhea. Immunologic studies showed most of the infants to have inverted ratios of T-cell subsets, greatly increased immunoglobulin levels, and circulating immune complexes. Lymphopenia was not common, as it is in adult patients. Infectious agents responsible for opportunistic infections in this series included Pneumocystis carinii, herpesviruses, particularly cytomegalovirus, and C. albicans. Bacterial infections were common, and gram-negative sepsis was the major cause of death in the seven infants who have died. At autopsy, two infants had disseminated lymphadenopathic Kaposi's sarcoma. These observations suggest the likelihood of transplacental, perinatal, or postnatal transmission of an as yet unidentified infectious agent that causes this disease.