Disruption of lysosomal targeting is associated with insecticidal potency of juvenile hormone esterase

Juvenile hormone esterase (JHE; EC 3.1.1.1), which is intrinsically involved in regulation of development of some insect larvae, is rapidly removed from the hemolymph by the pericardial cells. Lys-29 and Lys-524, which are implicated in the degradation of JHE, were mutated to Arg. Neither the half-life of the modified JHE in the hemolymph nor the catalytic parameters were changed significantly, but when combined, these mutations resulted in apparent failure of lysosomal targeting in the pericardial cell complex. A hypothesis for the mechanism of reduced efficiency of lysosomal targeting is presented. Infection of larvae with a recombinant baculovirus expressing the modified JHE resulted in a 50% reduction in feeding damage compared with larvae infected with the wild-type virus, thus demonstrating improved properties as a biological insecticide. These data demonstrate that alteration of specific residues of JHE that disrupted lysosomal targeting, dramatically increased the insecticidal activity of this protein.     

Pustular and erythrodermic psoriasis complicated by acute respiratory distress syndrome

To investigate the mechanisms of the hypolipidemic effect of monatepil, a new class of calcium antagonists with alpha 1-adrenergic blocking activity, we examined the effects of the drug on low-density lipoprotein (LDL) receptor activity and the level of LDL receptor mRNA present in cultured human skin fibroblasts. At concentrations of 2 x 10(-5) M, monatepil increased the binding (248 +/- 43%; mean +/- SD), internalization (374 +/- 18%), and degradation (145 +/- 2%) of 125I-LDL in human skin fibroblasts (n = 3, p < 0.05). Treatment of human skin fibroblasts with 2 x 10(-5) M of monatepil for 6 hours resulted in an increase in LDL receptor mRNA to 163% of the control level (n = 2), as shown by Northern blot analysis. Our results suggest that the hypolipidemic clinical effects of monatepil may be due to increased LDL receptor activity.     

Mutations in purine nucleoside phosphorylase deficiency

PURPOSE: The aim of this study was to investigate the incidence of unexpected malignant uveal melanoma in the age of ultrasound diagnostics and to highlight the reasons for misdiagnosis. PATIENTS AND METHODS: All eyes were surgically removed and histologic examination was performed between 1981 and 1995. The eyes were investigated for the incidence of uveal melanoma, and the history of the unexpected malignant melanoma of the uvea or ciliary body highlighted. RESULTS: 225 (18.7%) eyes with malignant melanoma out of 2583 enucleated eyes were found. Eight (3.6%) of 225 were clinically unexpected. The clinical misdiagnoses were secondary angle closure or open angle glaucoma (6), retinal detachment (5), iritis (1), scleritis (1), cataract (4) and an intraocular mass that was believed to be a metastasis of a colon carcinoma. Seven of eight eyes were blind, and one eye had light perception only. The longest follow up before enucleation was 13 years. On three eyes diagnostic ultrasound was reportedly performed without specific diagnosis of uveal melanoma. Surgery was performed on four eyes for reasons of uncontrollable intraocular pressure or retinal detachment up to five years before enucleation. Histologic diagnoses were 3 epitheloid-type, 2 spindel-type and 3 necrotic melanoma of the uvea. Four eyes showed scleral invasion by tumor cells and one eye an invasion into the episcleral space. CONCLUSIONS: Even today the rate of unexpected uveal melanoma, according to our study is 3.6%. Therefore, all blind eyes without visualisation of the posterior pole should be examined with ultrasound in order to diagnose an uveal melanoma prior to enucleation.