Pharmacologically distinct vasoactive intestinal peptide binding sites: CNS localization and role in embryonic growth.

In vitro autoradiography with [125I]vasoactive intestinal peptide revealed that the vasoactive intestinal peptide analogue, stearyl-norleucine17 vasoactive intestinal peptide, reported to be inactive at adenylyl cyclase-linked receptors in astrocytes, displaced a subset of vasoactive intestinal peptide binding sites on rat brain sections. These sites were widespread in adult rat brains and enriched in the olfactory bulb and thalamus, and corresponded to previously demonstrated GTP-insensitive vasoactive intestinal peptide binding sites. Stearyl-norleucine17 vasoactive intestinal peptide also identified receptors in rat lung and liver. In the adult brain, the stearyl-norleucine analog displaced only GTP-insensitive vasoactive intestinal peptide binding sites. In contrast, stearyl-norleucine17 vasoactive intestinal peptide-displaceable sites in the embryonic day 9 mouse appeared to include both GTP-sensitive and GTP-insensitive binding sites. This observation suggested the presence of an embryonic vasoactive intestinal peptide receptor with distinct pharmacological properties. Treatment of whole cultured mouse embryos with stearyl-norleucine17 vasoactive intestinal peptide resulted in stimulation of embryonic growth, with the stearyl-norleucine analog equipotent to vasoactive intestinal peptide, but less efficacious at higher concentrations (10(-7) M). Embryonic growth was inhibited by pituitary adenylyl cyclase-activating peptide and 8-bromoadenosine 3',5'-cyclic monophosphate. In addition, 8-bromoadenosine 3',5'-cyclic monophosphate inhibited stearyl-norleucine17 vasoactive intestinal peptide-stimulated growth. The results of the current study support the hypothesis that vasoactive intestinal peptide regulation of early postimplantation embryonic growth occurs, at least in part, independently of adenylyl cyclase stimulation.

Recrudescence of treated neurosyphilis in a patient with human immunodeficiency virus.

The natural history of syphilis has been altered by the human immunodeficiency virus (HIV) epidemic. Treatment of patients coinfected with syphilis and HIV is currently controversial; progression and relapse of neurosyphilis have been reported. This case report documents failure of primary treatment and neurosyphilitic recrudescence. In a 32-year-old HIV-positive woman with syphilis who had no additional sexual contacts, the disease progressed to neurosyphilis despite three intramuscular doses of penicillin. After extended intravenous penicillin treatment, neurosyphilis later recurred and re-treatment was necessary. Because many urban centers are affected by high rates of sexually transmitted diseases, including common coinfections of syphilis and HIV, further efforts should be made to identify subsets of patients who may be at high risk of syphilitic recrudescence.

Inhibition of murine embryonic growth by human immunodeficiency virus envelope protein and its prevention by vasoactive intestinal peptide and activity-dependent neurotrophic factor.

Intrauterine growth retardation and neurodevelopmental handicaps are common among infants born to HIV-positive mothers and may be due to the actions of virions and/or maternally derived viral products. The viral envelope protein, gp120, is toxic to neurons, induces neuronal dystrophy, and retards behavioral development in neonatal rats. Vasoactive intestinal peptide, a neuropeptide regulator of early postimplantation embryonic growth, and the neuroprotective protein, activity-dependent neurotrophic factor, prevent gp120-induced neurotoxicity. Whole embryo culture of gestational day 9.5 mouse embryos was used to assess the effect of gp120 on growth. Embryos treated with gp120 exhibited a dose-dependent inhibition of growth. gp120-treated embryos (10(-8) M) grew 1.2 somites in the 6-h incubation period, compared with 3.9 somites by control embryos. Embryos treated with gp120 were significantly smaller in cross-sectional area and had significantly less DNA and protein than controls. Growth inhibition induced by gp120 was prevented by cotreatment with vasoactive intestinal peptide or activity-dependent neurotrophic factor. gp120 may play a role in the growth retardation and developmental delays experienced by infants born to HIV-positive mothers. Vasoactive intestinal peptide and related factors may provide a therapeutic strategy in preventing developmental deficits.

MR of thoracic cord compression caused by epidural extramedullary hematopoiesis in myelodysplastic syndrome.

Spinal cord compression caused by extramedullary hematopoiesis is a rare complication of chronic anemic states, most frequently occurring in patients with beta-thalassemia. We report the MR appearance of extramedullary hematopoiesis resulting in cord compression in a patient with a myelodysplastic syndrome, which was isointense with the spinal cord on T1-weighted images and markedly hypointense on fast spin-echo T2-weighted images, and that demonstrated enhancement.

Peptide analogs of the beef heart mitochondrial F1-ATPase inhibitor protein.

Peptide analogs which correspond to the conserved region of the natural ATPase inhibitor protein from beef heart, Candida utilis, and Saccharomyces cerevisiae mitochondria were synthesized by solid-phase methodologies and tested for ATPase inhibitory activity. These peptides were found to be potent inhibitors of F1-ATPase-catalyzed ATP hydrolysis in acidic reaction media, having I50 values of 1.1 +/- 0.4 microM, 10 +/- 5 microM, and 48 +/- 19 microM, respectively. These results closely match those obtained for the naturally occurring inhibitor proteins. Additional peptides that correspond to the beef heart beta-subunit near the binding site of the beef heart inhibitor protein and that possess a substantial homology with the conserved region of the inhibitor protein were synthesized. Several of these peptides were found to be inhibitors of the ATPase activity. The best inhibitor, with an I50 value of 20 +/- 3 microM, was the peptide resembling the beef heart beta-subunit comprising amino acids 394-413. This peptide most closely resembles the peptides derived from the conserved region of the inhibitor protein. The insertion of five glycine residues between the charge clusters in the beta-394-413 peptide resulted in a peptide which was able to stimulate the hydrolysis of ATP.