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Human recombinant interferon-alpha (IFN alpha) restricted viral replication in human immunodeficiency virus- (HIV) infected T cells and monocytes. With T cells, reverse transcriptase (RT) activity in culture fluids was reduced threefold from that of control infected cells by IFN treatment, but HIV p24 antigen levels were unchanged. In contrast, levels of p24 antigen and RT activity in lysates of IFN-treated infected cells were threefold greater than those of controls. These differences suggest that the mechanism for IFN-induced antiviral effects in HIV-infected T cells resides in the terminal events (assembly and release) of the virus replication cycle. Monocytes treated with IFN at the time of virus challenge showed no p24 antigen or RT activity, no HIV-specific mRNA, and no proviral DNA in cells for up to 3 weeks after infection. IFN treatment of chronically infected monocytes also decreased virus replication, as assessed by p24 antigen, mRNA and RT detection assays. However, levels of proviral DNA in the IFN-treated and control HIV-infected cells were indistinguishable. The presence of large quantities of proviral DNA in cells with little or no evidence for active transcription documents a situation approaching true microbiological latency.

A fast progressing lethal case of neuroleptic malignant syndrome (NMS) complicated by disseminated intravascular coagulation (DIC) is presented. The fulminant course is infrequent and relates NMS to malignant hyperthermia. Muscular relaxation in combination with fluid load dramatically decreased the temperature, but the catastrophic course of this case was so advanced that the currently recommended treatment of NMS was impossible.

The interaction of human recombinant interferon-gamma (rIFN-gamma) with human polymorphonuclear cells (PMN) was investigated. Bolton-Hunter radioiodinated rIFN-gamma bound to PMN in a specific and saturable manner. Eleven hundred binding sites were observed with a Ka of 0.56 x 10(10) M-1. Binding to PMN was rapid with a K1 of 9 x 10(5) M-1 sec-1 at 4 degrees C. At 37 degrees C binding was complete within 6 min. About 50% of bound ligand was internalized within 30 min at 37 degrees C. The receptor demonstrated moderate lability at 37 degrees C in culture. After 1 h at 37 degrees C, PMN lost 80% of their 125I-rIFN-gamma binding sites. This loss was reversed in part by the presence of interleukin-1 in the culture, but not tumor necrosis factor. These studies provide a framework for further investigation into the signalling process of rIFN-gamma on PMN.

Leishmania mexicana mexicana promastigotes, axenic amastigotes, and amastigotes derived from Vero cells were examined for de novo purine synthesis and mechanisms of purine salvage. Both promastigotes and axenic amastigotes were incapable of de novo purine synthesis, as shown by the lack of [14C]formate and [14C]glycine incorporation into purine nucleotide pools. However, the ready incorporation of [14C]hypoxanthine, [14C]adenine, and [14C]guanine suggested that purine salvage pathways were operating. In addition, a significant percentage (greater than or equal to 60%) of the total label from these purine precursors was associated with adenylate nucleotides. Nucleotide pool levels of axenic amastigotes were consistently greater but the specific activities were less than those of promastigotes, suggesting a slower rate of purine metabolism in the axenic amastigote form. Similar results were obtained from amastigotes isolated from infected Vero cells.

The absorption of 3H-labeled adenine, adenosine, hypoxanthine, and 14C-labeled inosine by normal rat erythrocytes, Plasmodium bergheri-infected erythrocytes and saponin released "free parasites" was measured. The uptake of these labeled substrates by normal rat erythrocytes occurs both by diffusion and mediated transport systems. Similar absorptive mechanisms for these substrates also were observed for both Plasmodium berghei-infected erythrocytes and "free parasites." Data from inhibition studies using purine base and nucleoside analogues indicate the presence of three distinct transport loci in the normal erythrocyte for adenosine-inosine, hypoxanthine, and adenine and two loci in the infected erythrocyte and "free parasite" for adenosine-inosine-hypoxanthine and adenine. The initial metabolism of 3H-adenosine by the "free parasite" also was examined. A double isotope technique was used to follow the separate metabolic fates of the purine base and ribose moieties of adenosine. The data suggest a possible conversion of adenosine to the purine base and ribose moiety and subsequent uptake of the purine base by the parasite. In addition, a powerful adenosine deaminase inhibitor (2-deoxcoformycin) significantly reduced the uptake of 3H-adenosine by the "free parasites." Chromatographs of aliquots from postincubation media show the tritium label to be associated predominately with adenosine in the presence of 2-deoxycoformycin and with isoine and hypoxanthine in the absence of the inhibitor.

Promastigotes of Leishmania braziliensis panamensis absorbed the purines adenine, hypoxanthine, adenosine and inosine by a combination of diffusion and mediated components. When the uptake rates for these substrates were corrected for diffusion and compared, the purine bases adenine and hypoxanthine were transported at a significantly slower rate than the purine nucleosides adenosine and inosine. Competitive interactions among those purines tested confirmed the presence of mediated and diffusion components and suggested that three transport loci may be operating (Fig. 6). The first transport locus, designated Locus 1, transported inosine, Locus 2, the purine bases hypoxanthine and adenine and Locus 3, adenosine. In addition, adenine and hypoxanthine inhibited the uptake of one another competitively. A comparison of Ki values derived from double reciprocal plots of labelled hypoxanthine and adenine uptake in the presence of the unlabelled substrates as inhibitors suggested that adenine has a greater affinity for the transport locus.

The maximal rate of glucose influx in Hymenolepis diminuta decreased when CL- in the incubation medium was replaced with acetate, benzoate, bicarbonate, formate, hippurate, iodide, lactate, mandelate, or nitrate. The effect of Cl- deletion on glucose influx using any of these anions was reversed when worms were incubated in Krebs-Ringer saline for 15 min. Glucose in the incubation medium increased 36Cl- influx in worms, while in Na+-free media the presence of glucose had no effect on 36Cl- influx. Influx of 10 mM 36Cl- in H. diminuta was inhibited by unlabeled Cl- in the incubation medium. Hymenolepis diminuta accumulated glucose aginst an apparent concentration differnce when Cl- in the incubation media was replaced with acetate, bicarbonate, or nitrate. The influx of Cl- appears couples with the influxes of Na+ and glucose, but the data do not show whether the influxex of these molecules are mediated through a common "carrier."

Viable Leishmania promastigotes and amastigotes were detected by epifluorescence microscopy with fluorescein diacetate being used to mark living parasites and the nucleic acid-binding compound ethidium bromide to stain dead cells. This procedure is superior to other assays because it is faster and detects viable intracellular as well as extracellular Leishmania. Furthermore, destruction of intracellular pathogens by macrophages is more accurately determined with fluorescein diacetate than with other stains. The procedure may have applications in programs to develop drugs and vaccines against protozoa responsible for human and animal disease.

Prader-Willi Syndrome (PWS) is a relatively common complex genetic disorder that is diagnostically and therapeutically challenging to health-care professionals. Nursing observations of significant neonatal feeding problems may assist in identification of the infant with PWS. Once nurses become familiar with the characteristics of this multi-system condition, they can provide specific assistance to PWS infants and their families.