Occupational illness and poison control centers. Referral patterns and service needs.

In a study of occupational illness reported to a regional poison control center and to gauge the center''s outreach and services, we did follow-up interviews of 301 case contacts over a 6-month period. We ascertained referral routes, reasons for contacting the poison control center, and awareness of the center''s function. For 122 cases a nonphysician was the initial poison control center contact. Of the nonphysician contacts, 41 had already consulted a health care provider and been referred to the poison control center for assistance. Of the 70 persons with exposure, only 21 had been aware before their exposures that poison control center services might include occupational chemical illness consultation. Physicians and nonphysicians expressed similar reasons for contacting the poison control center, with 118 of 301 identifying the need for an exposure hazard risk assessment. These data suggest that although those contacting a poison control center because of occupational illness include a variety of cases, they have many similar service needs.     

Inhibition of HIV infection by a novel CD4 domain 2-specific monoclonal antibody. Dissecting the basis for its inhibitory effect on HIV-induced cell fusion.

HIV use the CD4 molecule as their primary cellular receptor. Residues in the N-terminal domain (D1) of CD4 are crucial to HIV attachment through the gp120 envelope component. However, other regions of CD4 appear to be required subsequently for virus- and cell-cell fusion. Little is understood of the post-binding steps which may differ between HIV variants. We report a novel anti-CD4 mAb that does not block CD4/gp120 binding, but that does efficiently block both viral infection and cell-cell syncytia formation, and define its contact site as residues in CD4 D2 using both mouse/human CD4 chimeras and CD4 substitution mutants. We also investigated the basis for its antiviral effect. Using the CD4 D2 specific mAb, we identify another conserved step in HIV infection, as evidenced by its ability to neutralize a broad range of primary isolates and T cell-line passaged strains. Monovalent forms of the mAb were used to determine if its activity was due to masking of the D2 epitope, to steric inhibition, or bivalency. Our data indicate that both binding site and bivalency of the mAb underlie its potency. The need for bivalency is not simply explained by affinity, because monovalent forms can displace the intact mAb and reverse its protective effect. These results provide evidence that binding of the D2-specific mAb prevents structural alterations necessary for membrane fusion.     

The effects of mechanical stretching on fetal rat lung cell prostacyclin production

A model system was used to determine the effect of stretch on prostacyclin (PGI) production by organotypic fetal rat lung cultures grown on gelatin foam in vitro, measured by RIA of 6-keto-PGF1_α (6KF) in the culture medium. The stretching apparatus was programmable for stretch of varying frequency and duration. The effective stimuli for PGI production were: continuous pulsatile stretch> intermittent pulsatile stretch> permanent stretch (p<0.05). The rate of PGI production was greatest in the first 15min of pulsatile stretch and was associated with a 70% increase in cAMP production (p < 0.05). When the effect of magnitude of stretch was compared (15% vs 28% extension), there was a significant increase with a maximum in the 28% stretch group double that of the 15% stretch group (p<0.01). PGI production in response to pulsatile stretching was inhibited by indomethacin but not by pretreatment with cortisol. These results suggest that the production of PGI by lung cells may be significantly affected by the frequency and magnitude of pulsatile stretching.     

Metabolism and biological activity of all-trans 4,4-difluororetinyl acetate

All-trans [11-³H]4,4-difluororetinyl acetate was synthesized by treating methyl all-trans [11-³H]4-oxoretinoate with diethylaminosulfurtrifluoride, followed by reduction and acetylation of the product. After oral administration of the radioactive difluoro analog in oil to rats, difluororetinol, difluororetinyl palmitate and related esters, 4-oxoretinol, 4-oxoretinoic acid and polar conjugated derivatives were identified in the intestine, liver, kidney and / or blood. The major metabolic products were difluororetinyl palmitate and related esters, which were stored in the liver. The presence of the difluoro analog in liver oil from treated rats was confirmed by ¹⁹F-NMR spectroscopy. Neither retinol nor retinyl esters were detected as products of the metabolism of the difluoro analog. Nonetheless, all-trans difluororetinyl acetate showed 26 ± 12% of the biological activity of all-trans retinyl acetate in the rat growth assay. Presumably, the difluoro analog is active per se in growth rather than by conversion to retinol or to one of its known growth-promoting metabolites. In general, however, the difluoro analog was metabolized in a manner very similar to vitamin A. The vitamin A moiety of administered difluororetinyl acetate and retinyl acetate was poorly stored (1.8–3.3%) in the liver of vitamin A-depleted rats, confirming and extending past reports that the liver storage mechanism is severely impaired when initial liver stores are very low.     

Molecular Determinants of Mouse Neurovirulence and Mosquito Infection for Western Equine Encephalitis Virus

Western equine encephalitis virus (WEEV) is a naturally occurring recombinant virus derived from ancestral Sindbis and Eastern equine encephalitis viruses. We previously showed that infection by WEEV isolates McMillan (McM) and IMP-181 (IMP) results in high (∼90–100%) and low (0%) mortality, respectively, in outbred CD-1 mice when virus is delivered by either subcutaneous or aerosol routes. However, relatively little is known about specific virulence determinants of WEEV. We previously observed that IMP infected Culex tarsalis mosquitoes at a high rate (app. 80%) following ingestion of an infected bloodmeal but these mosquitoes were infected by McM at a much lower rate (10%). To understand the viral role in these phenotypic differences, we characterized the pathogenic phenotypes of McM/IMP chimeras. Chimeras encoding the E2 of McM on an IMP backbone (or the reciprocal) had the most significant effect on infection phenotypes in mice or mosquitoes. Furthermore, exchanging the arginine, present on IMP E2 glycoprotein at position 214, for the glutamine present at the same position on McM, ablated mouse mortality. Curiously, the reciprocal exchange did not confer mouse virulence to the IMP virus. Mosquito infectivity was also determined and significantly, one of the important loci was the same as the mouse virulence determinant identified above. Replacing either IMP E2 amino acid 181 or 214 with the corresponding McM amino acid lowered mosquito infection rates to McM-like levels. As with the mouse neurovirulence, reciprocal exchange of amino acids did not confer mosquito infectivity. The identification of WEEV E2 amino acid 214 as necessary for both IMP mosquito infectivity and McM mouse virulence indicates that they are mutually exclusive phenotypes and suggests an explanation for the lack of human or equine WEE cases even in the presence of active transmission.