Reaction or infection: topical chloramphenicol treatment.

Chloramphenicol is a topical treatment that is used widely, especially in wounds around the eyes. In our practice there have been a number of cases of delayed hypersensitivity to chloramphenicol that has been mismanaged initially as an infective cellulitis. We hope to share some of our experience of this uncommon reaction to highlight the delayed reaction that can occur with topical application of this drug.

Expression of a truncated keratin 5 may contribute to severe palmar--plantar hyperkeratosis in epidermolysis bullosa simplex patients.

Epidermolysis bullosa simplex are dominant disorders of skin fragility characterized by intraepidermal blistering upon mild mechanical trauma. Skin fragility is caused by expression of either an abnormal keratin 5 or an abnormal keratin 14 protein, which compromises the structure and function of the keratin cytoskeleton of basal cells. We report an epidermolysis bullosa simplex patient with a novel single base substitution (A-->T1414) that changes the lysine residue at amino acid 472 to a non-sense codon (K472X). This change predicts the synthesis of a truncated keratin 5, missing 119 amino acids, including the entire tail domain and the highly conserved KLLEGE motif at the carboxy terminus of the 2B domain of the central rod. Expression of an altered keratin 5, of predicted mass and pI for the product of the K472X allele, was documented by one- and two-dimensional western blots of protein extracts from patient skin. Ultrastructural analysis of the patient's nonhyperkeratotic skin was remarkable for basal keratinocytes with dense and irregular keratin filaments proximal to the basement membrane. Keratinocytes, transfected with a cDNA carrying the A-->T1414 non-sense mutation, overexpressed a truncated keratin 5, and showed a disorganized and collapsed keratin filament cytoskeleton. This is the second epidermolysis bullosa simplex patient reported with a premature termination mutation in the KLLEGE motif. The remarkable occurrence of severe palmar--plantar hyperkeratosis in both patients suggests that the keratin 5 tail domain may have unrecognized, but important, normal functions in palmar-plantar tissues.

Epidermolysis bullosa simplex: a keratin 5 mutation is a fully dominant allele in epidermal cytoskeleton function.

To explore the relationship between abnormal keratin molecules, 10-nm intermediate filament (IF) organization, and epidermal fragility and blistering, we sought to determine the functional consequences of homozygosity for a dominant keratin defect. We describe a family with an autosomal dominant skin-blistering disorder, epidermolysis bullosa simplex, Koebner subtype (EBS-K), that has a novel point mutation, occurring in the keratin 5 gene (KRT5), that predicts the substitution of an evolutionarily conserved lysine by an asparagine residue (K173N). Unlike previous heterozygous mutations located within the initial segment of domain 1A of keratin molecules, K173N heterozygosity did not result in severe disease or clumping of keratin filaments. One family member was found to be homozygous for the K173N allele, having inherited it from each of her affected first-cousin parents. Despite a lack of normal keratin 5 molecules, and an effective doubling of abnormal molecules, available for heterodimerization with keratin 14 during IF formation, there were no significant differences in the clinical severity or the ultrastructural organization of the keratin IF cytoskeleton of the homozygous individual. These data demonstrate that the K173N mutation behaves as a fully dominant allele and indicate that a limited number of abnormal keratin molecules are sufficient to impair cytoskeletal function and elicit epidermal fragility and blistering.

Autosomal dominant cyclic hematopoiesis: exclusion of linkage to the major hematopoietic regulatory gene cluster on chromosome 5.

Autosomal dominant cyclic hematopoiesis (ADCH), or cyclic neutropenia, is a genetic disorder characterized by cyclic oscillations of neutrophils and other blood cells. To determine if the gene for ADCH mapped within the major hematopoietic regulatory gene cluster at 5q23.3-q33.3, we tested five families with ADCH for genetic linkage between the disorder and loci on chromosome 5q. Two-point analyses gave significant evidence in favor of excluding linkage between ADCH and the hematopoietic genes granulocyte-macrophage colony-stimulating factor (CSF), interleukins 3, 4, 5, and 9, and the receptor of macrophage-CSF. Furthermore, the exclusion data provide evidence for rejecting the hypothesis that ADCH may be encoded by a new gene mapping within this cluster.

Spatial distribution of biochemical parameters indicating biomass and community composition of microbial assemblies in estuarine mud flat sediments.

The spatial distribution of communities was examined in estuarine mud flat sediments by the biochemical analysis of the lipids and lipid components extracted from the sediments. Total phospholipid was used as a measure of total biomass, and fatty acids were used as indicators of community composition. Comparisons were made among 2- by 2-m (location) and 0.2- by 0.2-m (cluster) sampling plots by using a nested analysis of variance to design an optimal sampling strategy to define the microbial content of a large, relatively homogenous area. At two of the three stations, a 2- by 2-m plot was representative of the station, but 0.2- by 0.2-m areas were in no case representative of the station. The biomass measured by the extractable phospholipid and the total lipid palmitic acid showed excellent correlation with the fatty acid "signatures" characteristic of bacteria, but showed a lower correlation with the long-chain polyenoic fatty acids characteristic of the microfauna.

Dynamics of mirex and its principal photoproducts in a simulated marsh system.

Three simulated marsh systems were constructed, containing sediment, marsh plants, oysters, blue crabs, fiddler crabs, and two species of top minnows. Seawater entered each of the pools by flowing across a trough, two of which contained Mirex bait. Tidal fluctuations were simulated. Samples of water, bait, and animals were periodically analyzed. All animals concentrated Mirex. Three photoproducts accumulated on the bait particles, and both oysters and one species of fish accumulated one of the photoproducts.

Blue crab mortality: interaction of temperature and DDT residues.

Serial observations of DDT-contaminated and uncontaminated salt marshes in the norther Gulf of Mexico were made in November and December, 1973. Blue crab (Callinectes sapidus) mortalities observed in the DDT-contaminated marsh during this period were correlated with reduced daily temperature minima. Gas chromatographic analysis of hepatopancreas and swimmeret muscle tissue of dead and dying crabs revealed total DDT residue concentrations as high as 39.0 ppm and 1.43 ppm, respectively. It is suggested that the DDT body burdens and reduced temperatures interact to produce acutely toxic effects. Several physiological and behavioral mechanisms are proposed.

Movement of mirex from sediment and uptake by the hogchoker, Trinectes maculatus.

Mirex contaminated sediments of the static test retained virtually all of the insecticide over a 4 week period. About 40% of the initial concentration was lost from the sediment under constant flow conditions. Mirex in water was directly related to levels of mirex in sediment. Mirex in water reached an equilibrium during the first week and declined over the following 3 weeks. Uptake of mirex by tissues showed a dose dependent relationship. Accumulation of the insecticide increased over time and did not appear to reach an equilbrium. Residues in the muscle of fish increased significantly with time (pless than.01) and test concentration (pless than.01). Mirex in the liver of fish increased significantly with time (pless than.05) of the flow-through test. Declinging levels of mirex in water indicated mirex was absorbed from the water by the fish. Considerably more mirex, however, was gained by the fish than was lost from the water. Thus the fish probably absorbed a significant amount of mirex from the sediments.