Blood lead on a traffic-free island.
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Biomedical subjects
Publications and source records attributed to R R Jones.
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Leukotriene B4 is a highly potent leukocyte chemotactic compound. It has been identified in chamber fluid and scale from psoriatic skin lesions, in which epidermal neutrophil infiltration is reported to be one of the earliest pathologic events. The ability of leukotriene B4 to reproduce the inflammatory events of psoriasis, by topical application to the skin of normal human volunteers, was thus studied. Persistent visible inflammatory reactions were elicited by application of amounts of leukotriene B4 as low as 5 ng, and the maximum diameters of the reactions were dose-related up to at least 500 ng. The visible reactions appeared 12-24 h after initial application of leukotriene B4, and persisted for several days, leaving brownish pigmentation and scaling at 7 days. Histologic examination showed intraepidermal neutrophil microabscesses at 24 h, but these had resolved by 48 h. A mixed, perivascular neutrophil and mononuclear cell infiltrate was seen in the dermis at 24 h, becoming predominantly mononuclear after 24 h. Nonspecific chemical irritant contact dermatitis was excluded by the absence of reactions to high doses of two chemically similar metabolites of arachidonic acid which lack significant in vitro chemokinetic activity. These experiments provide further evidence for the role of leukotriene B4 in the pathogenesis of psoriasis, and may lead to the development of an experimental model of the inflammatory events in psoriasis, and of a simple in vivo test of neutrophil function.
Various criteria have been used for the diagnosis of urticarial vasculitis, and for the classification of patients with chronic urticaria. In the present study, semithin Epon-embedded sections were obtained from fifteen patients using a method of fixation optimal for the preservation and examination of the dermal microvasculature. This allowed patients to be classified according to the presence or absence of significant endothelial cell pathology. This feature proved a more reliable indicator of associated humoral abnormalities than the nature of the perivascular infiltrate as seen on paraffin-embedded sections. Endothelial cell necrosis per se was a rare event and could not be used as a reliable criterion for the diagnosis of urticarial vasculitis. Most cases showed either endothelial hypertrophy or shrinkage.
Two cases of subcutaneously administered hydrocarbon based products are presented and the literature reviewed. The toxicity associated with subcutaneous administration is limited to the site of injection producing cellulitis and sterile abscess formation. Management is discussed with emphasis on the importance of incision and drainage of developing abscesses. Perceived toxicity and ready availability of these products suggests that similar exposures can be expected.
This study examined the tendency of observers to make less reliable recordings of behavioral events when a calibrating observer is absent. Experienced observers in 4 different research sites coded videotapes of family interaction using the multicategory system developed at each site. 60 tapes were coded simultaneously by randomly selected observer pairs (overt reliability assessment) and 40 tapes were coded independently by 2 observers who did not know that their entries could be compared (covert assessment). Within site, intraclass correlations (ICCs) were computed separately for both forms of reliability assessment and a variety of behaviors. Overt ICCs were very high for most behaviors in all 4 systems. The corresponding covert reliabilities were significantly lower. Covert decline was conspicuous in the first 10 min of a 1-hour coding session. Hence, observer fatigue was not its principal cause. Apparently, observers lapse into a less attentive "set" prior to coding without a partner. This tendency is most discernible when a highly complex system is employed.
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Histopathological criteria were used to classify twenty-four patients with chronic urticaria into three groups, which were then studied to establish whether circulating immune complexes (CICs), complement activation and deposition of immunoreactants are confined to patients with urticarial vasculitis. Group I (three patients) had classical urticarial vasculitis, and two of these patients showed hypocomplementaemia with evidence of C3 conversion and deposition of immunoreactants in lesional and uninvolved skin. Ten patients (group 2) with a dense perivascular mixed-cellular infiltrate had normal or raised complement levels and infrequent evidence of C3 conversion. Immunoreactants were detected only in their lesional skin. Eleven patients (group 3) had only a sparse perivascular infiltrate. In this group, complement was normal and immunofluorescence was essentially negative. Cryoglobulins were detected in group I patients only. Monoclonal rheumatoid factor and C1q binding were positive in all group I patients, half the group 2 patients and none of the group 3 patients. This study suggests that urticaria and urticarial vasculitis form a disease continuum, and identifies a group of patients with features intermediate between urticarial vasculitis and ordinary urticaria.
Mutant strains of the yeast Saccharomyces cerevisiae that require branched-chain amino acids must be supplemented with large concentrations (up to 10 mM) of these amino acids to satisfy their nutritional requirement. The utilization of one branched-chain amino acid, leucine, was examined in several leul strains of yeast grown aerobically in a glucose-ammonium salts minimal medium containing a limiting concentration (0.2 mM) of leucine. In this medium, the leucine requirement of the auxotrophic strains could be reduced by valine, another branched-chain amino acid. Increasing the valine concentration increased the cell yields of cultures and also reduced the levels of 3-methyl-1-butanol detected in the medium by gas chromatography. The concentration of 3-methyl-1-butanol was reduced from 122.0 to 48.9 muM when 5.0 mM valine was supplemented to limiting-leucine cultures. The amino acids isoleucine, threonine, norleucine, norvaline, alpha-amino-butyrate, alanine, and glycine also spared the leucine requirement of leucine auxotrophs, most likely because they resembled leucine and competed for its uptake. We propose that leucine analogs restrict the entry and degradation of leucine and thus reduce its conversion to 3-methyl-1-butanol, a major component of fusel oil.
Analysis of serum from a patient with cutaneous leukocytoclastic vasculitis showed a mixed cryoglobulin with a monoclonal IgM kappa-antiglobulin component (6.5 mg/ml), strong rheumatoid factor activity (latex titre 1/5000), and positive serological tests for syphilis (fluorescent treponemal antibody-absorbed and Treponema pallidum haemagglutination assay). After removal of antiglobulin activity by immunoabsorption with heat-aggregated gammaglobulin all serological test results for treponemal infection became negative. Serological tests for syphilis and rheumatoid factor on the supernatant from whole serum (minus cryoglobulin) remained positive though at a lower titre (latex 1/1250). Cryoglobulin isolated from whole serum retained rheumatoid and TPHA reactivity but was negative in the FTA-ABS test. The IgM and IgG cryoglobulin components purified by gel filtration on Sepharose showed no antitreponemal reactivity even when tested individually. Reducing the concentration of cryoglobulin to 1.5 mg/ml by plasma exchange converted the test results for syphilis to doubtful-positive or negative. These results indicated that high concentrations of antiglobulin activity may be associated with falsely positive specific antitreponemal test results and that this phenomenon depends on the concentration of cryoglobulin in the test sample.
Peripheral blood monocytes from a patient with pyoderma gangrenosum and paraproteinaemia showed defective phagocytosis; longitudinal observations demonstrated an association between the defect, the level of paraprotein and the clinical activity of the pyoderma. Treatment with Melphalan led to a reduction in the paraprotein level and remission of the pyoderma and was accompanied by normalization of monocyte function. After 8 months remission the paraprotein level rose again and was accompanied by a recurrence of the monocyte defect; shortly after this the pyoderma recurred. Pre-incubation of normal monocytes with the patient's plasma or immunoglobulin fractions revealed that a similar defect could be induced in normal cells by the patient's monomeric IgG. The patient's serum also had anti-heparin activity and the relationship between this and the phagocytic defect was explored. These studies indicate a possible pathogenetic mechanism underlying the association between pyoderma gangrenosum and monoclonal gammopathy.
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Multiple biopsies from a patient with a pruritic papular eruption of endogenous origin demonstrated a sequence of histopathological changes which varied markedly with the age of the lesion. Early lesions showed marked papillary oedema but no evidence of epidermal involvement. The next phase was characterized by the appearance of focal spongiosis and intra-epidermal vesiculation without involvement of the stratum corneum. Late lesions were characterized by residual spongiosis in the epidermis and groups of pyknotic nuclei in a parakeratotic stratum corneum. It would seem that this sequence of events is due to the elimination of papillary oedema through the epidermis. The fact that this process produces changes indistinguishable from those seen in eczema may indicate the eczema itself is a condition characterized by sub-epidermal oedema in which the epidermis is involved only as a secondary event. The title TEEPO (trans-epidermal elimination of papillary oedema) is suggested as a suitable acronym for this phenomenon. The term PEEPO (papular eruption with elimination of papillary oedema) is proposed for the eruption seen in this patient.
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