The relationship between neuropsychological/perceptual performance and socioeconomic status in children with learning disabilities.
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Biomedical subjects
Publications and source records attributed to D C Morrison.
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Comparable groups of diabetic patients asymptomatic of neuropathy (Group A), with chronic painful polyneuropathy (Group B) and painless polyneuropathy causing recurrent foot ulceration (Group C) were studied for differences in pedal blood flow, peripheral somatic and autonomic neuropathy and vascular calcification. Blood flow abnormalities detected by doppler waveform analysis, and consistent with reduced peripheral vascular resistance, were found in all three diabetic patient groups. The abnormalities were of similar severity in Group A and B but generally more marked in Group C. Tests of peripheral somatic nerve function became progressively more abnormal from Group A to Group C. Autonomic neuropathy was equally severe in Groups B and C, although mild abnormalities were recorded in diabetic patients asymptomatic of neuropathy. A similar pattern was seen for vascular calcification in the tarsal and metatarsal arteries: marked in both neuropathic groups (B and C) but mild in Group A. It was concluded that abnormal blood flow consistent with reduced peripheral vascular resistance is very common in the feet of diabetic patients whether or not they are symptomatic of neuropathy, and is most severe in those with chronic painless polyneuropathy and recurrent foot ulceration. No clear relationship was found between autonomic nerve dysfunction and the degree of abnormality of blood flow.
The factor structure of the Revised Behavior Problem Checklist (RBPC) was examined in a large sample of suburban kindergarten children. Teacher-rated dimensions of Conduct Disorder, Attention Problems-Immaturity, Anxiety-Withdrawal, and Psychotic Behavior were closely replicated, and a new factor labeled Unmotivated-Isolated was also revealed. These principal components were consistent across gender and across subsamples of children differing as to risk status for learning failure. Evidence was found for the divergent validity of the externalizing dimensions of Conduct Disorder and Attention Problems-Immaturity with respect to criterion measures of alternative behavior ratings, cognitive functioning, and academic achievement. Parent-rated components of Conduct Disorder, Attention Problems-Immaturity, Hyperactive-Impatient, Tense-Withdrawn, Anxiety, and Passive-Conforming were less clearly validated, and parent-teacher agreement was modest. It was concluded that the RBPC shows promise for the assessment of preschool-aged children and that narrow-band externalizing dimensions of inattentive versus conduct-disordered behavior are reasonably distinct at this age.
A variety of bacterial lipopolysaccharide (LPS) preparations with highly defined primary polysaccharide chemical structure and/or aggregate macromolecular composition have been employed to examine the molecular requirements for activation of the classical and alternative pathways of human serum complement. Evidence is presented for two independent modes of polysaccharide dependent activation of the APC by LPS. One mechanism is dependent upon specific O-antigen polysaccharides and the second is defined by a specific L-glycero-D-mannoheptose/glucose region of the core oligosaccharide. LPS O-antigen polysaccharide but not core oligosaccharide determinants can convert sheep erythrocytes to cells capable of initiating the APC. The data presented provide convincing evidence that the tertiary assembly of individual LPS subunits into an aggregate macromolecule is a critical determinant in the expression of APC activity by LPS. The results of these studies provide strong evidence that CPC activation by LPS is restricted to the Re-chemotype and isolated lipid A. LPS isolated from other R-chemotypes as well as native wild type LPS preparations do not activate the CPC, in spite of the fact that the former LPS preparations contain more lipid A than polysaccharide on a percentage by wt basis. The presence of core polysaccharide L-glycero-D-mannoheptose, which provides a critical recognition role for activation of the APC, appears to negatively regulate CPC activation in a similar inverse relationship. In addition, the presence of polysaccharide containing LPS subunits in synthetic mixed LPS micellar aggregates can also restrict CPC activation by Re LPS subunits, most probably by steric hindrance at the LPS macromolecular surface. Our data are consistent with the hypothesis that activation of either pathway of human serum complement by a given LPS preparation is a mutually exclusive event dictated by the presence or absence of L-glycero-D-mannoheptose.
In this chapter, current concepts about the mechanisms of action of endotoxin are reviewed. Particular attention is focused upon endotoxin-induced production of soluble mediators from macrophages and mononuclear cells and on the potential contribution of these mediators to endotoxin shock. In many cases, the interrelationships between these mediators as primary and/or secondary consequences of endotoxin stimulation of mononuclear phagocytes are discussed. Final comments address the relevance of these mediators to the therapy of endotoxin shock.
Endotoxemia causes neutrophil sequestration in the pulmonary vascular bed. Such sequestration may be a critical initiating event in the generation of microvascular injury, although the mechanisms that lead to this localization are not understood. To investigate these phenomena, the following study employed intravenous pulses of 111Indium-tropolonate-labeled neutrophils (111In-neutrophils), which circulated in the rabbit with normal kinetics and responded in a manner indistinguishable from unlabeled, circulating neutrophils in response to an intravenous injection of purified endotoxic lipopolysaccharide (LPS) or epinephrine. Pulmonary sequestration of 111In-neutrophils was assessed by quantitative external gamma camera scintigraphy of a lung suprahilar region of interest. Noninvasive assessment of radioactivity by this method accurately reflected total lung radioactivity, which was shown by autoradiography to be confined to the injected 111In-neutrophils. Intravenously administered LPS caused a marked, dose-dependent sequestration of 111In-neutrophils in the pulmonary vasculature, and exhaustive ultrastructural autoradiography showed discretely radiolabeled neutrophils located within pulmonary capillaries. A distinct effect was seen with an intravenous injection of as little as 100 ng per rabbit (i.e., 500 pg/ml blood). A 5-min ex vivo pretreatment of 111In-neutrophils with 10 ng to 10 micrograms/ml LPS in heat-inactivated plasma (which resulted in retention of as little as 500 pg LPS per 10(7) neutrophils) also caused dose-dependent pulmonary sequestration of the pretreated 111In-neutrophils but did not cause generalized neutropenia in recipient rabbits. There was no evidence of complement activation on the surface of pretreated neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)
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We have examined the killing of E. coli and kinetics of lipopolysaccharide (LPS) release after the exposure of the bacteria to normal human serum (NHS) and sera deficient in complement components, or with inactivated complement components. LPS of the galactose epimerase-deficient strain E. coli J5 were specifically radiolabeled by growing the bacteria in a medium containing [3H]galactose. Exposure of the washed bacteria to NHS resulted in a significant reduction (greater than 99%) in viability within 15 min and the concomitant release of radiolabeled LPS. However, maximal release of LPS was consistently 30% of the total radiolabel incorporated into the LPS molecules. The amount of tritium-labeled LPS released was shown to be directly proportional to the concentration of bacteria exposed to NHS, suggesting that release of LPS was not limited by the availability of some critical serum component(s). The consumption of complement in NHS by incubation with E. coli was demonstrated by decreased alternative and classical pathway-specific hemolytic activity. The use of Factor D-depleted and VEM-treated human sera demonstrated that, with these bacteria, both the alternative and classical pathways of complement contribute to bacterial killing and release of LPS. It is noteworthy that, in VEM-treated and Factor D-depleted sera, the rate of killing and the kinetics of LPS release were somewhat slower as compared to control serum. Bacterial killing in C7-depleted and C9-deficient human sera was minimal. Neither killing nor LPS release occurred in heat-inactivated (56 degrees C, 30 min) human serum. The amount of [3H]LPS released by C9-deficient serum was qualitatively similar to the amount released by the action of NHS. Tritium-labeled LPS was not released in C7-depleted serum. These data indicate that bacterial killing can be dissociated from LPS release, and suggest that, whereas LPS release may be necessary for the bactericidal effects of serum complement, it is probably not sufficient to effect killing. Furthermore, a significant fraction of LPS can be removed from the outer membrane of the bacteria without an apparent affect on viability.
Lipopolysaccharides (LPS) have been isolated from culture supernatants and from cell lysates after the in vitro phagocytosis of E. coli by murine macrophages. By using E. coli radiolabeled specifically in the LPS component with [3H]galactose, our studies have shown that the macrophage-"processed" LPS is enhanced with respect to its immunostimulatory activity in comparison with control phenol-water-extracted LPS. As assessed by its ability to induce interleukin 1 production in naive macrophages or proliferation in cultures of murine splenocytes, the macrophage-processed LPS is between 10- and 100-fold greater in specific activity. Evidence is presented for both structural and chemical alterations in the LPS macromolecule.
We have investigated the ability of gangliosides isolated from murine brain to modulate macrophage metabolism. LPS elicits a profound increase in glucose consumption by cultured resident macrophages. When highly purified mouse brain gangliosides are added to macrophage cultures, a modest inhibition of baseline glucose utilization occurs. Both disialogangliosides and trisialogangliosides mediate this effect. In the absence of serum, these gangliosides may be toxic to cultured macrophages. GT1b is the only brain ganglioside tested that specifically inhibited LPS-induced macrophage metabolism. Sialic acid appears to be a necessary component of the gangliosides, although it is not sufficient to induce inhibition. Asialoganglioside and free sialic acid have no effect on macrophage metabolism in comparison with intact gangliosides. The inhibition of LPS-induced metabolism may be explained by the ability of LPS to form stable molecular complexes with both disialogangliosides and trisialogangliosides. These experiments also suggest that the ganglioside content of macrophages may influence functional responses of macrophages to exogenous stimuli.
The mechanism whereby bacterial lipopolysaccharide (LPS) exerts its biologic effects on mammalian cells is unknown. Plasma membrane gangliosides bind bacterial toxins and have been implicated in modulating the effects of a variety of immunoregulatory substances. We investigated the possibility that gangliosides can inhibit the effect of lipopolysaccharide on Fc-dependent phagocytosis by murine peritoneal macrophages. Protein-free lipopolysaccharide preparations significantly inhibited Fc-mediated phagocytosis (less than 71% of control) at concentrations of 100 ng/ml or greater after 90 min of incubation. The inhibitory effect of LPS (1 micrograms/ml) was blocked when macrophages were incubated with mono-, di-, or trisialogangliosides (25-50 micrograms/ml). Neither asialoganglioside nor sialic acid alone were capable of blocking the effect of LPS. When chromatographed separately on a Sepharose 4B column, LPS and trisialoganglioside had different elution profiles. LPS and trisialoganglioside coeluted, however, when premixed at 37 degrees C for 60 min and then applied to the column. Therefore, abrogation of the effect of LPS on Fc-dependent phagocytosis may occur as a consequence of direct interaction between LPS and gangliosides. These data suggest that gangliosides may modulate the response of macrophages to bacterial lipopolysaccharide.
C3H/HeJ mice were immunized intraperitoneally (i.p.) with lipopolysaccharide (LPS)-lipid A-associated protein (LAP) complexes or with purified protein-free LPS prior to lethal i.p. or intravenous Salmonella typhimurium LT2 challenge. Our results demonstrated that these Salmonella-hypersusceptible mice can be effectively protected against 1,000 100% lethal doses of S. typhimurium LT2 (i.e., 1,000 viable bacteria) administered by intravenous challenge when previously immunized with LAP-LPS complexes. In contrast to these results, immunization with LPS afforded markedly less protection regardless of the route of challenge, thus suggesting that the LAP portion of LAP-LPS complexes may be necessary for inducing protection against Salmonella infections. For most experiments, antigens were emulsified in complete Freund adjuvant (CFA); however, the CFA portion of the vaccine was suggested not to be an essential component for the induction of immunity to Salmonella infections, since equivalent levels of protection were obtained when it was omitted from the vaccine. The induction of immunity to murine salmonellosis by prior immunization with CFA-LAP-LPS was demonstrated not to be a transient phenomenon, since C3H/HeJ mice were still protected against lethal S. typhimurium LT2 challenge as late as 225 days postimmunization.
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Reductions in dietary fat have been recommended in the prevention of coronary heart disease. Because entrees contribute substantially to total meal fat content, we evaluated a cafeteria-based intervention for increasing the purchase rate of low-fat entrees (M = 6.83 g) relative to nonlow-fat entrees (M = 25.59 g). The intervention included a poster listing the benefits of a LF diet and the daily LF entrees (i.e., broiled or baked chicken and fish dishes). During 6 days per phase, food selections (N = 3,264) were monitored by trained observers. The intervention, which cost $80.00, produced significant increases (i.e., from 20% to 35%) in the purchase rate of LF entrees.
Endotoxin activity was detected in several commercial allergen extracts. Epicutaneous skin testing using purified lipopolysaccharide (LPS) alone or mixed with allergen extracts demonstrated that LPS had no effect on test results. We conclude that endotoxin present in allergen extracts is unlikely to have any practical implication for epicutaneous skin testing with these extracts.
A method for the synthesis of a photoactivatable, iodinatable, and thiol-cleavable derivative of bacterial lipopolysaccharide (LPS) is described using sulfosuccinimidyl 2-(p-azidosalicylamido)-1,3'-dithiopropionate. The method described is applicable to LPS from both smooth and rough bacteria. Evidence is presented that the coupling reaction occurs primarily to phosphoethanolamine residues localized to the inner core region of the LPS. Radioiodination of the derivatized LPS results in a product with a specific activity of 1.8-2.5 microCi/micrograms. Experiments comparing the activity of native and derivatized S-form LPS suggest that the synthesis has not introduced major alterations in the biological properties of the LPS. The feasibility of this derivatized LPS as a molecular probe to investigate LPS binding targets in biological systems is suggested by experiments showing ultraviolet light-dependent cross-linking, thiol-dependent cleavage, and subsequent transfer of radioiodine to both monoclonal anti-LPS antibody and bovine serum albumin. The latter interaction has been demonstrated to be highly selective in protein mixtures containing serum albumin in solution with LPS.