Biomedical subjects
C Thompson
Publications and source records attributed to C Thompson.
Efficacy of a recombinant endotoxin neutralizing protein in rabbits with Escherichia coli sepsis.
Gram-negative bacterial sepsis is associated with endotoxemia and a high mortality rate. In previous studies, we demonstrated the therapeutic benefit of an anti-lipopolysaccharide factor isolated from amebocytes of Limulus polyphemus, and of a recombinant version of this protein, termed endotoxin neutralizing protein (ENP), in rabbits challenged with purified lipopolysaccharides. To assess the benefit of ENP in treating a live bacterial infection, we established a rabbit model of Escherichia coli (E. coli) peritonitis and bacteremia with high mortality despite gentamicin treatment. Twenty-four pairs of New Zealand white rabbits were challenged intraperitoneally (IP) with E. coli O18ac K1 in 5% porcine mucin (mean bacteria per dose = 2.5 x 10(8)). The animals were treated with intravenous (i.v.) gentamicin (2.5 mg/kg), and with either ENP (5 mg/kg) or saline i.v. at 1 hr after E. coli challenge. All rabbits were bacteremic 1 hr after challenge (geometric mean 4.1 +/- 1.2 x 10(4) cfu/mL). Peak geometric mean serum endotoxin (2.62 v 10.54 EU/mL, P = .013) and tumor necrosis factor (TNF) (2540 v 6438 TNF units/mL, P = .046) concentrations were lower in ENP-treated animals as compared to control animals. Seven of 24 animals treated with ENP survived 24 hr compared with 4 of 24 controls (Kaplan-Meier analysis, P = .19). However, in the subgroup of 13 paired animals in whom bacteremia was eliminated by gentamicin treatment, 5 of 13 ENP-treated animals survived 24 hr, compared with 1 of 13 controls (Kaplan-Meier analysis, P = .032).(ABSTRACT TRUNCATED AT 250 WORDS)
Intraindividual variation among pregnant adolescents: a pilot study and conceptual discussion.
There is little empirical research or theory on intraindividual variation (mood changes) during adolescence, and virtually no research on intraindividual variation during adolescent pregnancy. This pilot study illustrates the need for research on pregnant adolescents' moods and their impact on survey reliability and validity. Fourteen adolescents kept diaries for six consecutive weeks during their pregnancies. The diary entries were analyzed for affective tone, emotional lability, and contextuality. A conceptual discussion is presented that questions the psychometric properties of data gathered using one time, self-report measures with pregnant adolescents because of their fluctuating mood states. Hypotheses are generated for future testing in this area and a call is made for a new area of research on intraindividual tension during adolescent pregnancy.
Kangaroo care: research results, and practice implications and guidelines.
Results of two studies of the effects of 2 to 3 hours of kangaroo care (KC), one a randomized trial of 25 premature infants in open-air cribs and the other a pilot of 6 premature infants who were at least 24 hours postextubation, who were cared for in incubators are reviewed. Both studies incorporated a pretest/posttest control group design. Heart rate and abdominal skin temperature rose for KC infants during KC. Heat loss did not occur during KC, and infants slept more during KC. Kangaroo care had a comforting effect on infants and their mothers. Apnea and periodic breathing episodes dropped during KC for incubator infants. Suggestions and guidelines for selection of infants and practice based on these studies are presented.
Spatial integration of compound gratings with various numbers of orientation components.
PURPOSE: The human foveal visual system in a detection task was recently modeled as a simple image processor comprising low-pass filtering due to the optical modulation transfer function of the eye, high-pass filtering (lateral inhibition) due to the neural modulation transfer function of visual pathways, addition of internal neural noise, and detection by a local matched filter, the efficiency of which decreases with increasing grating area. The applicability of this model was now tested by studying spatial integration for sums of various numbers of cosine gratings with different orientations. METHODS: Binocular root-mean-square contrast sensitivity was measured as a function of area for sums of cosine gratings (n = 1 to 16) with the same contrast, phase, and spatial frequency but with an orientation difference of 180/n between the components. RESULTS: In agreement with the model, contrast sensitivity increased in proportion to the square root of grating area at small areas. When grating area exceeded its critical value, the increase saturated, and contrast sensitivity then became independent of area. The critical area and maximum contrast sensitivity of spatial integration first decreased with an increasing number of components, reaching minima at n = 5 to 6, but increased thereafter. A plausible explanation for the variation of critical area and maximum sensitivity could be the variation of the amount of contour and detail per unit area in the sums of cosine gratings. Critical area divided by maximum sensitivity squared refers to the contrast energy threshold at small grating areas. It was independent of the number of components but, because of lateral inhibition, decreased in inverse proportion to spatial frequency squared. Contrast energy threshold as a function of normalized grating area (grating area divided by critical area) also was independent of the number of components and decreased in inverse proportion to spatial frequency squared. CONCLUSIONS: Within the framework of the local matched filter model, the dependency of contrast sensitivity on the grating area and number of orientation components resulted from the decrease in the efficiency of contrast energy collection, which was probably due to the increasing amount of contour and detail in the stimulus to be detected.
Use of new Escherichia coli/Streptomyces conjugative vectors to probe the functions of the two groEL-like genes of Streptomyces albus G by gene disruption.
Streptomyces albus G contains two groEL-like genes encoding three related proteins [Guglielmi et al., J. Bacteriol. 173 (1991) 7374-7381; Mazodier et al., J. Bacteriol. 173 (1991) 7382-7386]. Two proteins, HSP58 and HSP18, are synthesized from a single start codon site in groEL1. HSP18 may be a processed form of HSP58 or the result of early termination after frameshifting. The third protein, HSP56 is encoded by groEL2. In order to determine the physiological roles of these different proteins, both groEL genes were mutagenized by using a new approach for obtaining insertions in the streptomycete chromosome. Escherichia coli plasmids containing fragments homologous to groEL1 or groEL2 are unable to replicate in Streptomyces. They were introduced into S. albus by conjugation with E. coli. We then screened for mutants in which groEL1 or groEL2 had been disrupted due to recombination events (single or double crossover) at specific sites. Using this approach, the functionally indispensable domain of HSP58 was localized to within 249 amino acids of the N-terminus. HSP58 was not detected in the mutant generated by the most upstream insertion into the groEL1 coding sequence. However, HSP18 was synthesized in this mutant after heat shock. This groEL1 mutant was not impaired in growth in the 30-41 degrees C temperature range and SDS-PAGE analysis showed its overall pattern of gene expression to be indistinguishable from the parental strain. The inability to generate strains containing groEL2 disruptions strongly suggests that HSP56 is indispensable for growth.(ABSTRACT TRUNCATED AT 250 WORDS)
Lack of involvement of nitric oxide in NMDA-induced neuronal cell death in cortical culture.
In primary cultures of rat cerebral cortex, N-methyl-D-aspartate causes widespread neurotoxicity. Inhibitors of the nitric oxide generating the enzyme nitric oxide synthase has been shown to attenuate the effects of N-methyl-D-aspartate in a number of neuronal systems both in vivo and in vitro. In our experiments, the nitric oxide synthase inhibitor N-nitroarginine was ineffective at blocking neurotoxicity induced by N-methyl-D-aspartate. Cyclic guanine monophosphate, known to be synthesized in response to nitric oxide was demonstrably inhibited by identical treatments with N-nitroarginine in sister cultures. We conclude that although nitric oxide is produced in response to N-methyl-D-aspartate, it is neither necessary nor sufficient for neurotoxicity.
Use of fluorescence in situ hybridization to confirm the interpretation of a balanced complex chromosome rearrangement ascertained through prenatal diagnosis.
A balanced complex chromosome rearrangement (BCCR) involving 3 chromosomes with 4 breakpoints, was identified in a 36-yr-old woman who was studied because her fetus was discovered to have an unbalanced reciprocal translocation (7q;10q). Analysis of high resolution bands and the application of fluorescence in situ hybridization has identified the BCCR as der(7)t(7;10)(q21.13;q23.33)ins(21;7)(q21.3;q11.22q21.13), der(10)t(7;10)(q21.13; q23.33), der(21)ins(21;7)(q21.3;q11.22q21.13). Alternate segregation of the BCCR appears to be favoured, and has resulted in two pregnancies with an unbalanced chromosome constitution.
Importance of diabetic foot admissions at Middlemore Hospital.
AIMS: To investigate the costs and mortality associated with admission for diabetic foot problems. METHODS: Identification of patients by codes for diabetes and peripheral vascular disease from routinely collected hospital discharge data. Information was collected retrospectively from charts. Post discharge outcome was assessed by discussion with general practitioners. RESULTS: 357 patients accounted for 503 admissions. 11-15% of patients (n = 49) were admitted for diabetic foot problems. Patients with type 1 diabetes had shorter lengths of stay than those with type 2 diabetes, were more likely to be admitted with chronic renal failure and less likely to be admitted with ischaemic heart disease. Maori and Pacific Island patients with type 2 diabetes were admitted at a younger age than Europeans (53 (SD12) vs 56 (11) vs 69 (13) years respectively, p < 0.001). Admissions for diabetic foot problems resulted in the longest hospital stay in comparison with other causes (19 (1-184) days vs 8 (1-116)) days. Average cost per diabetic foot admission was $12,500 with a total annual cost of over $600,000. CONCLUSION: The diabetic foot is expensive and yet these costs are largely avoidable with improvement in patient education, motivation, monitoring and earlier intervention. It would be better to have in place improved community and hospital care before the predicted growth in the diabetic population associated with ageing.
Accessory cell function of keratinocytes for superantigens. Dependence on lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction.
A growing body of evidence points to a role for epidermal keratinocytes as active participants in immunologic reactions. Inasmuch as certain T cell-mediated skin diseases, such as psoriasis and atopic dermatitis, are triggered by microbial infection, we asked whether multipassaged human keratinocytes could provide the costimulatory signals necessary to induce autologous T cell proliferation in response to bacterial-derived super-antigens. On exposure to IFN-gamma, keratinocytes are induced to express HLA-DR and HLA-DQ class II MHC Ag, and the lymphocyte function-associated Ag-1 counter-receptor intercellular adhesion molecule-1 (ICAM-1). This change in keratinocyte phenotype is accompanied by the ability of these cells to support T cell proliferation induced by two different bacterial-derived superantigens, staphylococcal enterotoxins A and B. Superantigen-driven proliferation in the presence of IFN-gamma-treated keratinocytes was significantly inhibited (70-90% reduction) by mAb against the LFA-1 alpha- or beta-chain or ICAM-1. Proliferation was not inhibited by mAb against the CD28 ligands BB-1 or B7, even though these keratinocytes express BB-1. In addition to previous defined roles for class II MHC Ag, stimulation of LFA-1 on the T cells by ICAM-1 on the keratinocytes also plays an important costimulatory role in this superantigen-mediated response. The accessory cell capability of keratinocytes was not unique to superantigen driven responses as PHA, as well as anti-CD3 mAb also induced vigorous T cell proliferation when IFN-gamma-treated keratinocytes were added. However, IFN-gamma-treated keratinocytes consistently failed to provoke an allogeneic response. These data demonstrate that 1) keratinocytes can serve as accessory cells for T cell proliferation using a variety of different stimuli, 2) the LFA-1/ICAM-1 interaction plays a major role in keratinocyte-mediated costimulation, and 3) previous reports in which IFN-gamma-treated keratinocytes failed to support T cell proliferation to nominal or alloantigens, may reflect impaired Ag presentation via class II MHC molecules, rather than lack of necessary costimulatory signals. These findings highlighting the accessory cell function of keratinocytes may have implications for our understanding of the pathogenesis of immunologic disorders of the skin.
Neuropsychiatric aspects of HIV-1 infection in gay men: controlled investigation of psychiatric, neuropsychological and neurological status.
The aim of this study was to determine whether HIV infection is associated with psychiatric morbidity or neuropsychological impairment in asymptomatic and early symptomatic stages of disease in gay men. The subjects were 100 gay men (68 HIV-ve, 32 HIV+ve, 6 being CDC IV). All subjects were recruited at the time of requesting their first HIV test and the assessment was double-blind to HIV serostatus. There were no differences in psychiatric status or neuropsychological performance between the HIV-ve and HIV+ve groups. Multiple regression analysis and logistic regression were used to identify factors associated with psychiatric morbidity, neuropsychological impairment and subjective reporting of memory problems and physical symptoms for all 100 subjects. Previous psychiatric history and current illegal (non-dependent) drug use were associated with psychiatric morbidity, poor education was associated with neuropsychological impairment and psychiatric status (score on HAD and PSE) was associated with subjective reporting of memory problems and physical symptoms.
Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces distinct defects in the central nervous system.
N-CAM is abundantly expressed in the nervous system in the form of numerous structural variants with characteristic distribution patterns and functional properties. N-CAM-180, the variant having the largest cytoplasmic domain, is expressed by all neurons. The N-CAM-180-specific exon 18 has been deleted to generate homozygous mice unable to express this N-CAM form. The most conspicuous mutant phenotype was in the olfactory bulb, where granule cells were both reduced in number and disorganized. In addition, precursors of these cells were found to be accumulated at their origin in the subependymal zone at the lateral ventricle. Analysis of the mutant in this region suggests that the mutant phenotype involves a defect in cell migration, possibly through specific loss of the polysialylated form of N-CAM-180, which is expressed in the migration pathway. Subtle but distinct abnormalities also were observed in other regions of the brain.
Activated keratinocytes present bacterial-derived superantigens to T lymphocytes: relevance to psoriasis.
In the past, epidermal keratinocytes were felt to be primarily concerned with the barrier function of skin. During inflammatory and immune-mediated skin diseases, keratinocytes were only portrayed as being passive/inert targets for noxious agents produced by infiltrating leukocytes. This innocent bystander and/or 'brick and mortar' conceptualization of the keratinocyte must now be significantly modified to take into account the growing body of experimental in vitro and in vivo results that substantiate re-classification of keratinocytes as fully fledged members of the immune system (i.e. immunocytes). Because keratinocytes produce important primary cytokines, adhesion molecules, and mononuclear cell chemotactic factors; as well as functioning as accessory cells for resting T lymphocytes, they can initiate and perpetuate the inflammatory and immunological reactions in the skin which contribute to the pathobiology of psoriasis. This review will emphasize the dynamic contribution that epidermal keratinocytes make to cutaneous immunohomeostasis, with particular focus on the potential role of bacterial derived superantigens and their ability to stimulate resting T cell proliferation when presented by cytokine-activated keratinocytes.
Interference of immune globulin with measles and rubella immunization.
Passively acquired antibody may interfere with the active antibody response to live viral vaccines such as measles and rubella. To evaluate the duration of this inhibitory effect, we measured the measles and rubella antibody responses of Apache children immunized with measles, mumps, and rubella vaccine at varying intervals after administration of an immune globulin termed bacterial polysaccharide immune globulin (BPIG). This specific immune globulin contained measles and rubella antibody titers similar to those in standard intramuscularly and intravenously administered immune globulins. Antibody responses to measles vaccine were inhibited for up to 5 months after a BPIG dose of 80 mg IgG per kilogram of body weight, but responses to rubella vaccine were inhibited for only 2 months. Most children who had a decreased measles antibody response to primary measles, mumps, and rubella immunization given 1 1/2 to 4 months after BPIG administration responded to a booster immunization given 6 months after their last BPIG dose. We conclude that high doses of immune globulin (> 10 mg/kg) may inhibit the antibody response to measles for more than 3 months. We propose that the interval between administration of immune globulin and measles and rubella immunization be adjusted on the basis of the dose of immune globulin.
Antibody response of Navajo children primed with PRP-OMP vaccine to booster doses of PRP-OMP vs. HbOC vaccine.
We compared in 12- to 15-month-old American Indian infants the safety and immunogenicity of two licensed Haemophilus influenzae type b (Hib) conjugate vaccines, PRP-OMP (PedvaxHib) and HbOC (HibTITER), administered as booster vaccinations. All infants previously received PRP-OMP for their primary Hib vaccinations at 2 and 4 months of age. The geometric mean Hib antibody concentrations (microgram/ml) measured by radioactive antigen-binding assay for those receiving PRP-OMP (n = 17) or HbOC (n = 18) were 0.593 and 0.449, respectively, before boosting (P not significant) and 7.46 and 29.5 micrograms/ml, respectively, after boosting (P < 0.05). PRP-OMP recipients also had lower geometric mean IgG anti-Hib antibody concentrations than HbOC recipients (7.21 vs 28 micrograms/ml, P = 0.003) and lower bactericidal titers (3.18 vs. 15.4, not significant). We conclude that HbOC vaccine produced a significantly greater booster response than PRP-OMP vaccine when given at 12 to 15 months of age to children primed with two doses of PRP-OMP vaccine at 2 and 4 months of age.
Characterization of dinY, a new Escherichia coli DNA repair gene whose products are damage inducible even in a lexA(Def) background.
Bacteriophage Mu dX(Ap lac) was used to isolate a mutation in an Escherichia coli lexA(Def) strain representing a previously undescribed gene (dinY) which does not seem to be under the direct control of LexA. The insertion created a dinY::lacZ fusion in which beta-galactosidase expression required a DNA-damaging treatment (UV irradiation or mitomycin) and activable RecA protein. This strain showed a decreased Weigle reactivation of bacteriophage lambda. However, it was fully inducible for UV mutagenesis. Two-dimensional gel electrophoresis analysis identified two spots absent in the mutant which were both UV inducible only in the presence of activated RecA protein (RecA*). This finding suggests that the dinY::lacZ fusion lies in a gene either that is under the direct control of activated RecA or whose product undergoes RecA*-dependent posttranscriptional/posttranslational modification(s). The dinY gene may also control the expression of some other gene(s) and/or lie in an operon. The fusion was mapped at a position between 41 and 41.5 min on the E. coli chromosome, in the vicinity of the ruv operon.
Salivary testosterone levels and major depressive illness in men.
Explore the source record for details and available documents.
Detection and comparison of DNA adducts after in vitro and in vivo diesel emission exposures.
Development of methods to evaluate certain classes of polycyclic aromatic compounds (PAC) detected in complex mixtures to which humans are exposed would greatly improve the diagnostic potential of 32P-postlabeling analysis. Identification of DNA adduct patterns or specific exposure-related marker adducts would strengthen associations between observed DNA adducts and exposures to different environmental pollutants (e.g., kerosene, cigarette smoke, coke oven, and diesel). We have compared diesel-modified DNA adduct patterns in various in vitro and in vivo rodent model systems and compared them to DNA reactive oxidative and reductive metabolites of 1-nitropyrene. The formation of nitrated polycyclic aromatic hydrocarbon (nitrated PAH) DNA adducts, derived from the metabolism of diesel extract constituents, was enhanced relative to other PAH-derived DNA adducts via xanthine oxidase-catalyzed nitroreduction. These adducts were detectable only by the butanol extraction version of the postlabeling analysis. Five major DNA adducts were detected in human lymphocytes treated in vitro with diesel extract. A major adduct detected in human lymphocytes treated in vitro with diesel extract comigrated with a major adduct detected in lymphocyte DNA treated with benzo[a]pyrene (BaP) alone. Other adducts that co-migrated with the major BaP-derived adducts were detected in skin and lung DNA isolated from rodents topically treated with (50 mg) diesel extract and the major adduct detected in calf thymus DNA treated with rat liver S9 and diesel particle extract. Postlabeling of lung DNA isolated from rodents exposed via lung inhalation for 24 months to diesel combustion emissions resulted in the formation of a major nuclease-P1-sensitive DNA adduct that did not co-migrate with the major BaP-diol epoxide adduct.(ABSTRACT TRUNCATED AT 250 WORDS)