The biosphere below.
More than a mile below Earth's surface, tiny creatures thrive in searing heat and crushing pressure. Scientists think these microorganisms might teach us about the origins and evolution of early life.
Biomedical subjects
Publications and source records attributed to D Grossman.
More than a mile below Earth's surface, tiny creatures thrive in searing heat and crushing pressure. Scientists think these microorganisms might teach us about the origins and evolution of early life.
OBJECTIVES: To examine characteristics and experiences associated with gun ownership among parents of pediatric patients who attend urban pediatric clinics and to determine the receptivity of these parents to firearm injury prevention counseling. DESIGN: A focus group discussion was followed by a cross-sectional survey. SETTING: Four public pediatric clinics in a large metropolitan area were included. PARTICIPANTS: A focus group discussion was held with parents and was used to develop the questionnaire, which was then distributed over a 6-week period to parents accompanying children to the clinic. The anonymous, self-administered questionnaire was completed by 510 parents or guardians, with an 88% response rate. RESULTS: Twenty percent of respondents reported that they had a firearm in the home. Twenty-seven percent of respondents had experienced having a family member shot. Eighty-two percent of all respondents indicated that they would find information about the safest way to store a gun helpful or very helpful. Of all respondents, 47% would follow and an additional 37% would think over a provider's advice not to keep guns in the home. Gun owners were less inclined to report that they would follow this advice (19%), but 55% of the gun owners would think over this advice. Only 6% of all respondents reported that they would ignore or be offended by such advice. CONCLUSIONS: Children attending public urban pediatric clinics are exposed to guns in their homes, and their parents appear to be receptive to firearm injury prevention counseling from their child's health care providers.
Data regarding fever management were obtained through a retrospective or concurrent review of the medical records of 150 patients. For 41% of the patients studied, nurses notified physicians of the fever episode. The decision to treat fever was significantly influenced by fever intensity and the drawing of blood cultures, but not by age, length of hospital stay, or the duration of the fever episode. Despite recent evidence of the protective value of fever, the majority of fever episodes were treated. Acetaminophen alone, and acetaminophen in combination with physical cooling methods, were effective in lowering fever.
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The incidences of clinical and biological markers of atopy were investigated in 16 children with IgA nephropathy (IgAN) (group A) and in 22 with Henoch-Schönlein purpura nephritis (HSPN) (group B). The incidence of increased plasma IgE levels according to age-matched normal values was significantly higher in group B (17/22, 77%) than in group A (7/16, 44%) (P < 0.05). Although not significant, the incidences of positive RAST tests and of a history of typical atopic symptoms were also higher in group B [10/22 (45%) and 11/22 (50%), respectively] than in group A [4/16 (25%) and 5/16 (31%), respectively]. Moreover, IgE deposits were demonstrated by a peroxidase/anti-peroxidase method on cutaneous Langerhans and mast cells in 4 of 6 patients with HSPN. Thus immunoallergy might account, in some cases, for the cutaneous, intestinal and pulmonary signs observed in HSPN, but not in IgAN. We postulate stimulation of IgE-sensitized mast cells by specific antigens in the presence of IgA circulating immune complexes (CIC), release of vasoactive substances, increased capillary permeability and perivascular deposition of IgA CIC.
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A patient with mycosis fungoides that had progressed to tumor stage responded to chemotherapy and electron beam treatment, but 6 years later a peripheral neuropathy, extensive plaques, erythroderma, and enlarged pinnae containing acid-fast organisms developed while he was being treated with photopheresis. The skin lesions cleared with administration of rifampin and dapsone, but a reversal reaction biopsy specimen showed features of both mycosis fungoides and leprosy. This case raises the question of whether there may be an association between mycosis fungoides and leprosy.
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We report the deliberate ingestion of a superwarfarin product, brodifacoum, in a 39-y-old male. He presented with prothrombin and partial thromboplastin times of 150 and 113 sec, respectively. His coagulopathy was corrected by administration of blood products and phytonadione. To maintain normal clotting studies this patient required the highest maintenance dose of phytonadione, 200 mg/d, reported to date. The patient was able to tolerate this dose for 5 mo without adverse effects.
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A defining characteristic of superantigens is their ability to stimulate T cells based predominantly on the type of variable segment of the T cell receptor (TCR) beta chain (V beta). The V beta specificity of these toxins most likely results from direct contact between the toxin and the TCR, although the low affinity nature of this binding has prevented direct assessment of this interaction. To identify important functional sites on the toxin, we created chimeric enterotoxin genes between staphylococcal enterotoxins A and E (SEA and SEE) and tested the V beta specificity of the chimeric toxins. This approach allowed us to identify three amino acid residues in the extreme COOH terminus of these toxins that are largely responsible for their ability to stimulate either human V beta 5- or V beta 8-bearing T cells, or mouse V beta 3 or V beta 11. We also found that residues in the NH2 terminus were required for wild-type levels of V beta-specific T cell activation, suggesting that the NH2 and COOH ends of these superantigens may come together to form the full TCR V beta contact site. SEA and SEE also differ with respect to their class II binding characteristics. Using the same chimeric molecules, we demonstrate that the first third of the molecule controls the class II binding phenotype. These data lead us to propose that for SEA and SEE, and perhaps for all bacterial-derived superantigens, the COOH and NH2 termini together form the contact sites for the TCR and therefore largely determine the V beta specificity of the toxin, while the NH2 terminus alone binds major histocompatibility complex class II molecules. The predominant role of the COOH terminus of bacterial superantigens in determining V beta specificity resembles current models being proposed for virally encoded superantigens, suggesting that these molecules may demonstrate some structural relationship not seen at the amino acid level.
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This study examined the emetic activity of several staphylococcal enterotoxin type A and B (SEA and SEB, respectively) mutants that had either one or two amino acid residue substitutions. New sea gene mutations were constructed by site-directed mutagenesis; gene products were obtained with glycine residues at position 25, 47, 48, 81, 85, or 86 of mature SEA. Culture supernatants from Staphylococcus aureus RN4220, or derivatives containing either sea or a sea mutation, were analyzed for the ability to stimulate proliferation of murine splenocytes, as determined by incorporation of [3H]thymidine. Culture supernatants containing SEA-N25G (a SEA mutant with a substitution of glycine for the asparagine residue at position 25), SEA-F47G, or SEA-L48G did not stimulate T-cell proliferation, unlike supernatants containing the other substitution mutants. Purified preparations of SEA-N25G had weak activity and those of SEA-F47G and SEA-L48G had essentially no activity in the T-cell proliferation assay. All mutants except SEA-V85G, which was degraded by monkey stomach lavage fluid in vitro, were tested for emetic activity. SEA-C106A and two SEB mutants, SEB-D9N/N23D and SEB-F44S (previously referred to as BR-257 and BR-358, respectively), whose construction and altered immunological properties have been reported previously, were also tested in the emetic assay. Each mutant was initially administered intragastrically at doses of 75 to 100 micrograms per animal; if none of the animals responded, the dose was increased four-to fivefold. SEA-F47G, SEA-C106A, and SEB-D9N/N23D were the only mutants that did not induce vomiting at either dose tested; these three mutants had reduced immunological activity. However, there was not a perfect correlation between immunological and emetic activities; SEA-L48G and SEB-F44S retained emetic activity, although they had essentially no T-cell-stimulatory activity. These studies suggest that these two activities can be dissociated.
Streptococcus pyogenes (group A Streptococcus) has re-emerged in recent years as a cause of severe human disease. Because extracellular products are involved in streptococcal pathogenesis, we explored the possibility that a disease isolate expresses an uncharacterized superantigen. We screened culture supernatants for superantigen activity with a major histocompatibility complex class II-dependent T cell proliferation assay. Initial fractionation with red dye A chromatography indicated production of a class II-dependent T cell mitogen by a toxic shock-like syndrome (TSLS) strain. The amino terminus of the purified streptococcal superantigen was more homologous to the amino termini of staphylococcal enterotoxins B, C1, and C3 (SEB, SEC1, and SEC3), than to those of pyrogenic exotoxins A, B, C or other streptococcal toxins. The molecule, designated SSA, had the same pattern of class II isotype usage as SEB in T cell proliferation assays. However, it differed in its pattern of human T cell activation, as measured by quantitative polymerase chain reaction with V beta-specific primers. SSA activated human T cells that express V beta 1, 3, 15 with a minor increase of V beta 5.2-bearing cells, whereas SEB activated V beta 3, 12, 15, and 17-bearing T cells. Immunoblot analysis of 75 disease isolates from several localities detected SSA production only in group A streptococci, and found that SSA is apparently confined to only three clonal lineages as defined by multilocus enzyme electrophoresis typing. Isolates of one of these lineages, (electrophoretic type 2) are strongly associated with TSLS. The data identify SSA as a novel streptococcal superantigen that appears to be more related structurally to staphylococcal enterotoxins than to streptococcal exotoxins. Because abundant SSA production is apparently confined to only three streptococcal clonal lineages, the data also suggest that the SSA gene has only recently been acquired by S. pyogenes.
Scores on the K-SNAP, a new brief cognitive measure designed to assess neuropsychological functioning in adolescents and adults, were correlated with KAIT IQs, a comprehensive test that measures fluid and crystallized intelligence. The sample included 33 adolescent and adult patients hospitalized for depression. The K-SNAP correlated significantly higher with fluid than crystallized intelligence.
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Bovine leukemia virus (BLV) is transcriptionally silent in most circulating peripheral blood mononuclear cells (PBMCs) of animals with well-established infections. Using PBMCs from a newly infected sheep, we asked whether viral transcription proceeded differently during the initial months of infection, when the prevalence of BLV-infected cells and the host's immunological response change markedly. Shortly after being injected with BLV, the animal displayed a characteristic, transient increase in PBMCs that transcribed BLV when cultured. Even when transcriptionally competent PBMCs were most prevalent (1.2%), only rare cells in the circulation (1 in 50,000) contained enough BLV transcripts to be identified readily by in situ hybridization. However, at one point several weeks later, some PBMCs appeared to contain small amounts of BLV RNA as soon as they had been purified from blood. Throughout this period, BLV-transcribing PBMCs greatly outnumbered virus-producing cells, which were counted using a new infectious centers assay. Its viscous medium reduced cell to cell contact among PBMCs, enabling increased detection of BLV-producing cells at a time when virus-specific killer cells might be active. Early infection was polyclonal, and most infected PBMCs transcribed BLV upon being cultured. By 2 months after infection, provirus-containing cells were as abundant as they had been earlier, but few cells transcribed BLV. These results suggest that BLV-infected cells are more easily stimulated to transcribe the provirus and produce infectious virus during the early months of a new infection.