Small animal jet injection technique results in enhanced immunogenicity of hantavirus DNA vaccines

DNA vaccine evaluation in small animals is hampered by low immunogenicity when the vaccines are delivered using a needle and syringe. To overcome this technical hurdle we tested the possibility that a device developed for human intradermal medicine delivery might be adapted to successfully deliver a DNA vaccine to small animals. Disposable syringe jet injection (DSJI) does not currently exist for small animals. However, a commercialized, human intradermal device used to to administer medicines to the human dermis in a 0.1 mL volume was evaluated in Syrian hamsters. Here, we found that hantavirus DNA vaccines administered to hamsters using DSJI were substantially more immunogenic than the same vaccines delivered by needle/syringe or particle mediated epidermal delivery (gene gun) vaccination. By adjusting how the device was used we could deliver vaccine to either subcutaneous tissues, or through the skin into the muscle. RNA and/or antigen expression was detected in epidermal, subepidermal and fibroblast cells. We directly compared six optimized and non-optimized hantavirus DNA vaccines in hamsters. Optimization, including codon-usage and mRNA stability, did not necessarily result in increased immunogenicity for all vaccines tested; however, optimization of the Andes virus (ANDV) DNA vaccine protected vaccinated hamsters from lethal disease. This is the first time active vaccination with an ANDV DNA vaccine has shown protective efficacy in the hamster model. The adaptation of a human intradermal jet injection device for use as a method of subcutaneous and intramuscular jet injection of DNA vaccines will advance the development of nucleic acid based medical countermeasures for diseases modeled in hamsters.     

Silo gas exposure in New York state following the dry growing season of 1995

Exposure to silo gas is a recognized agricultural hazard. Silo gas produced from corn fermentation may consist of oxides of nitrogen and carbon dioxide. The presence of potentially lethal concentrations of nitrogen dioxide (NO2) within vertical silos has been well documented. The risk of silo gas exposure from other silage storage methodologies--including horizontal "ag-bags" and concrete bunkers--has been less well characterized. A dry growing season is known to be a factor for elevating nitrate levels in corn plants and can result in increased NO2 production. Farms in the northeastern United States faced drought conditions during the 1995 growing season. The New York State (NYS) Department of Health (DOH) and the New York Center for Agricultural Medicine and Health (NYCAMH) investigated four exposure incidents involving six farmworkers during September/October 1995. Four of these workers were hospitalized for multiple days, with two workers receiving treatment in intensive care units. The remaining two workers were treated in hospital emergency departments; one refused admission and left against medical advice. We monitored NO2 levels from "ag-bags" at several New York farms. For four days, outdoor concentrations of NO2 at one site remained in excess of the National Institute for Occupational Safety and Health's (NIOSH) immediately dangerous to life and health value (IDLH) of 20 ppm. As a result of the clinical and industrial hygiene data, and the growing season's abnormal weather conditions, DOH and NYCAMH issued statewide health hazard alerts and conducted educational activities to warn farmers and their families. The findings of this study reinforce the potential hazards associated with silo gas exposure and identify the use of ag-bags as a relatively new avenue for significant worker exposure.     

Pallister-Hall syndrome: clinical and MR features

A 4-month-old boy with polydactyly and bifid epiglottis was found to have a large sellar and suprasellar mass. When the diagnosis of Pallister-Hall syndrome was made, conservative management was elected. When the patient was 2 years old, the tumor had grown proportionally with the patient, and he was developing appropriately. Although rare, this entity is important to recognize not only for clinical diagnosis but also for appropriate management and genetic counseling.     

Activation of tyrosine receptor kinase plays a role in expression of long-term potentiation in the rat dentate gyrus

Long-term potentiation (LTP) in perforant path-granule cell synapses has been shown to be accompanied by an increase in glutamate release. The objective of this study was to examine the possibility that nerve growth factor (NGF), by activating tyrosine kinase, modulates glutamate release and, therefore, contributes to expression of LTP in dentate gyrus. The data indicate that NGF, in the presence of trans-1-aminocyclopentyl-1,3-dicarboxylate (ACPD), enhanced KCI-stimulated release and KCI-stimulated calcium influx in vitro and that these effects were blocked by the tyrosine receptor kinase (trk) inhibitor tyrphostin AG879. The data also indicate that NGF increased phosphorylation of trkA and the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) in dentate gyrus in vitro. In addition to its effects in vitro, tyrphostin AG879 inhibited the expression of LTP in perforant path-granule cell synapses and the accompanying increase in transmitter release. Analysis of phosphorylation of the two tyrosine kinase substrates trkA and ERK in synaptosomes prepared from untetanized and tetanized dentate gyrus revealed that LTP was associated with increased phosphorylation of both proteins; no evidence of such a change was observed in either tetanized or untetanized tissue prepared from tyrphostin-pretreated rats. These findings are consistent with the hypothesis that NGF, by interacting with trkA, triggers a sequence of tyrosine kinase-dependent phosphorylation steps that modulate glutamate release and calcium influx and impact on expression of LTP in dentate gyrus.     

The Massachusetts Behavioral Health Program Year 5: Transition to a New Managed Care Organization

Year 5 of the Massachusetts Behavioral Health Program was a transition to management by a new private managed care organization. Fifty-eight providers interviewed for an ongoing panel survey reported slightly lower levels of quality, access, utilization, and length of stay than a year earlier. Relationships with providers and advocates improved after an initial difficult period, while consumer and family involvement at all levels remained low. The greatest changes in managed care appeared to take place during the initial transition from fee-for-service care, but intractable problems continue, and full participation of stakeholders seems difficult to achieve.