IgE antibodies to Staphylococcus aureus in the hypereosinophilic syndrome

A 16-year old boy with a 10-year history of circulating eosinophilia was diagnosed having the hypereosinophilic syndrome (HES) based upon the exclusion of other disorders. Eight years after the onset of his condition, he had a subcutaneous staphylococcal abscess followed by lymphangitis, rare clinical features of HES. As measured by radioallergosorbent techniques, there were significantly high serum levels of IgE antibodies to Staphylococcus aureus. The clinical significance of these antibodies is unknown, but their production may be due to persistent antigenic stimulation.     

L-Arabinose-ornithine-Irgasan medium for differentiating Serratia species.

A semisolid medium (designated Serratia differentiation medium) containing L-arabinose, ornithine, and selective inhibitor was used to differentiate three clinically encountered Serratia species. The inhibitor, Irgasan DP-300, was incorporated to eliminate false-positive reactions from most remaining Enterobacteriaceae. The suspected Serratia colony was inoculated as a stab into the medium. Serratia marcescens was indicated by a change in color from olive to purple following 18 h of incubation, whereas S. rubidaea (not listed in Bergey's Manual of Determinative Bacteriology) was indicated by a change to bright yellow. S. liquefaciens (described in Bergey's Manual of Determinative Bacteriology [8th ed., 1974] as Enterobacter liquefaciens) produced a small purple band at the top of the medium and a yellow or yellow-green butt. Absence of growth and color change following incubation indicates that the suspected colony is a non-Serratia. Thirty-six Serratia strains and 97 other Enterobacteriaceae and Pseudomonadaceae strains were tested. Two strains of the non-Serratia Enterobacteriaceae (one each of Citrobacter freundii and Proteus morganii) and two strains of Pseudomonas aeruginosa produced a color change in the medium. All of the Serratia strains tested were correctly identified using this medium, while 96% of the other species tested were inhibited.     

Microbial infections,immunomodulation, and drugs of abuse

The use of recreational drugs of abuse has generated serious health concerns. There is a long-recognized relationship between addictive drugs and increased levels of infections. Studies of the mechanisms of actions of these drugs became more urgent with the advent of AIDS and its correlation with abused substances. The nature and mechanisms of immunomodulation by marijuana, opiates, cocaine, nicotine, and alcohol are described in this review. Recent studies of the effects of opiates or marijuana on the immune system have demonstrated that they are receptor mediated, occurring both directly via specific receptors on immune cells and indirectly through similar receptors on cells of the nervous system. Findings are also discussed that demonstrate that cocaine and nicotine have similar immunomodulatory effects, which are also apparently receptor mediated. Finally, the nature and mechanisms of immunomodulation by alcohol are described. Although no specific alcohol receptors have been identified, it is widely recognized that alcohol enhances susceptibility to opportunistic microbes. The review covers recent studies of the effects of these drugs on immunity and on increased susceptibility to infectious diseases, including AIDS.     

Aging-induced decrease in dopaminergic-stimulated phosphoinositide metabolism in rat brain.

Accumulation of [3H]inositol phosphate and [3H]inositol labeling of phosphoinositides were evaluated in brain slices of 3-, 6-, 12-, and 24-month-old Fischer-344 rats. The dopamine agonist, SKF38393, stimulated significantly lower accumulations of inositol trisphosphate, inositol bisphosphate, and inositol monophosphate in the striatum, hippocampus, and frontal cortex of 24-month-old rats compared with the 6-month-old animals. No differences, however, were observed between the 3, 6, and 12-month-old groups. Furthermore there were marked decrements of 41% to 58% in the labeling of phosphoinositides in the different brain regions of the aged animals. Dose-response studies in forebrain slices of the 6-month-old and 24-month-old animals showed aging-related decrements of 53% (p less than 0.001) and 48% (p less than 0.001) in the maximal SKF38393-stimulated labeling of phosphoinositides and accumulation of inositol phosphates, respectively. These data suggest that aging of the rat brain is associated with alterations in the basal turnover of the inositol cycle and in the sensitivity of the transduction pathway to dopamine receptor stimulation.     

Enhanced molecular volume of conservatively pegylated Hb: (SP-PEG5K)6-HbA is non-hypertensive

Recent studies have suggested that the "pressor effect" of acellular Hb is a consequence of perturbation of the macro-and microcirculatory system in multiple ways, and that PEGylation is an effective approach for controlling the same. In an attempt to confirm this concept, a new and simple thiolation mediated, maleimide chemistry-based conservative PEGylation protocol has been developed to conjugate multiple copies of PEG-chains to Hb. This approach combines the high reactivity of maleimides towards thiols with the propensity of iminothiolane to derivatize the epsilon-amino groups of proteins into reactive thiol groups, with conservation of their positive charge. One of the PEGylated products, namely (SP-PEG5K)6-HbA, that carries on an average six copies of PEG5000 chains per Hb, is non-hypertensive in hamster top load and in rat 50% exchange transfusion models. This hexa-PEGylated-Hb has (i) a hydrodynamic volume corresponding to that of an oligomerized Hb of 256kDa, (ii) a molecular radius of approximately 6.8 nm, (iii) high oxygen affinity, (iv) lowered Bohr effect, and (v) increased viscosity and colloidal osmotic pressure. These properties of (SP-PEG5K)6-HbA are consistent with the emerging new paradigms for the design of Hb based oxygen carriers and confirm the concept that the "pressor effect" of Hb is a multifactorial event. The thiolation mediated maleimide chemistry-based PEGylation protocol described here for the generation of (SP-PEG5K)6-Hb is simple, highly efficient, and is carried out under oxy conditions. The results demonstrate that a non-hypertensive PEG-Hb can be generated by conjugation of a lower number of PEG chains than previously reported.     

Filamentous phage DNA cloning vectors: a noninfective mutant with a nonpolar deletion in gene III

A filamentous phage derivative, fKN16, has been constructed from the tetracyclineresistance transducing phage fd-tet by deleting a 507-base-pair (bp) segment of phage gene III. In accord with the importance of the gene III protein in infection, the infectivity of fKN16 phage is less than 10^?8 that of fd-tet phage. In contrast to most gene III amber mutants, which are polar on the downstream phage genes VI and I, fKN16 should be a nonpolar mutant since its 507-bp deletion spans an integral number of coding triplets. And indeed, two phage traits that may depend on gene VI and I function—the level of phage production and packaging into unit-length virions—appear to be normal in fKN16. High phage production coupled with very low infectivity make fKN16 suitable as a vector for DNA cloning experiments requiring a high level of biological containment. The characteristics of fKN16 as a vector were investigated in detail, using HindIII fragments of phage λ DNA as model foreign DNA. fKN16 may also be useful in studying the role of the gene III protein in the filamentous phage life cycle.     

Autoimmunity in the relatives of patients with immunodeficiency diseases.

Autoimmune disorders are reportedly more frequent than expected in immunodeficient patients and in their relatives. The hypothesis that genetic factors related to immunodeficiency may predispose to the development of autoimmunity was studied in relatives of patients with variable immunodeficiency (VID), ataxia-telangiectasia (A-T), or X-linked infantile agammaglobulinaemia (X-LA). Close relatives of patients with VID or A-T had thyroid and gastric autoantibodies significantly more frequently than did control subjects. No abnormalities were detected in unaffected relatives of X-LA patients. The increased incidence of organ-specific autoantibodies in close relatives of VID patients was confined to those families with more than one member with immunodeficiency. These data suggest that there are at least two forms of VID, one of which is associated with familial autoimmunity. It is postulated that heterozygous carriers of the A-T gene and persons with genes involved in the development of VID may exhibit T-lymphocyte dysfunction which predisposes them to autoimmunity.