Retrospective review of antibiotic-associated serum sickness in children presenting to a paediatric emergency department.
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Ambulatory Care↗
Biomedical subjects
R J Phillips
Publications and source records attributed to R J Phillips.
Consequences of intrathymic TCR engagement by partial agonist on selection events and peripheral T cell activation program.
Functions elicited from mature T cells depend on the nature of the Ag. Thus, an agonist induces a larger set of cytokine responses than a partial agonist. Additionally, Ags present in the thymus influence both the selection of TCRs generated by gene rearrangement and the potential functional program of developing thymocytes. This can be approached by analysing the development of T cells in mice expressing the same transgenic TCR (tgTCR) under different conditions of intrathymic selection. H-2Kbm8 was found to act as a partial agonist for CD8+ T cells expressing a tgTCR specific for the H-2Kb alloantigen. Intrathymic exposure to full or to partial agonist affected the development of thymocytes at different stages, consistent with the respective CD8-independent and -dependent characteristic of the tgTCR/Ag interaction. The presence of the partial agonist led to the accumulation of a major population of thymocytes (tgTCR(high) CD4- CD8(low)) originating from TCR engagement at the immature single-positive CD8(low) stage as evidenced by: 1) results from reaggregated thymic organ culture in the presence of H-2(k/bm8) thymic stromal cells; 2) the absence of CD4+ thymocytes, the development of which depends on rearrangements of endogenous TCR alpha genes; and 3) the identification of the CD8(low) thymocytes as cycling cells. Peripheral CD8(low) T cells selected in an H-2(k/bm8) thymus expressed a partial functional program in response to H-2Kb, akin to the response of CD8(high) T cells to a partial agonist. The analysis of the molecular bases for partial reactivity revealed a correlation with inefficient AP-1, but efficient NF-kappaB transactivation.
Animals↗
Topography of the northern hemisphere of Mars from the Mars Orbiter Laser Altimeter.
The first 18 tracks of laser altimeter data across the northern hemisphere of Mars from the Mars Global Surveyor spacecraft show that the planet at latitudes north of 50 degrees is exceptionally flat; slopes and surface roughness increase toward the equator. The polar layered terrain appears to be a thick ice-rich formation with a non-equilibrium planform indicative of ablation near the periphery. Slope relations suggest that the northern Tharsis province was uplifted in the past. A profile across Ares Vallis channel suggests that the discharge through the channel was much greater than previously estimated. The martian atmosphere shows significant 1-micrometer atmospheric opacities, particularly in low-lying areas such as Valles Marineris.
Atmosphere↗
Nucleotide sequence of the 5'-terminus of Newcastle disease virus and assembly of the complete genomic sequence: agreement with the "rule of six".
We have determined the sequences of the 5' ends of three strains of Newcastle disease virus, permitting the assembly of the entire genomic sequence, which amounts to 15,186 nucleotides. This length is in agreement with the rule of six, which has been shown to determine replication efficiency in similar viruses. Comparison of the extreme 5' end of the trailer sequence with that of the 3'-terminal leader sequence of the virus reveals a high degree of complementarity. Variation between the 5'-terminal sequences of the different strains reveals the presence of alternative L gene polyadenylation signals, leading to correspondingly different trailer lengths.
Animals↗
Gastric volume detection after selective vagotomies in rats.
Rats receiving intragastric infusions of 2.5, 5.0, 7.5, or 10.0 ml of normal saline while their pylori are reversibly occluded suppress meal size to the smallest infusion and display a dose-dependent reduction across volumes [Phillips, R. J., and T. L. Powley. Am. J. Physiol. 271 (Regulatory Integrative Comp. Physiol. 40): R766-R779, 1996]. To evaluate the contributions of the vagus to this detection of gastric volume, groups prepared with different selective vagotomies and equipped with pyloric cuffs and gastric catheters were tested. Liquid diet consumption during a 30-min feeding bout was measured after infusions of 5.0 and 10.0 ml of normal saline on cuff-open and cuff-closed trials. Consistent with earlier observations, sham animals with cuffs closed exhibited volume-dependent suppression of food intake to the infusions, and completely vagotomized animals did not inhibit feeding in response to the loads. In cuff-closed trials, the suppression function slopes of the selective vagotomy groups were intermediate to those of the shams and the completely vagotomized animals. Furthermore, for the different groups, the extent of suppression after vagotomy was proportional to the density of the afferent innervation respective branches supplied to the stomach. Specifically, the group with the gastric branches spared (nonsignificantly attenuated in comparison to shams) and the group with only the hepatic branch spared (significantly attenuated with respect to shams) both still exhibited significant dose-dependent suppression slopes (compared with completes), whereas the group with only celiac branches spared was not significantly different from completely vagotomized animals. In sum, the vagus nerve mediates the detection of the gastric volumes tested, and the different branches of the vagus make distinctive contributions to this afferent feedback.
Animals↗
Communication from a computerized emergency department to general practitioners.
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Child↗
Afferent innervation of gastrointestinal tract smooth muscle by the hepatic branch of the vagus.
To survey the vagal hepatic branch afferent projections to and the terminal specializations in the gastrointestinal tract, male Sprague-Dawley rats were given subdiaphragmatic vagotomies, sparing only the common hepatic branch, and were injected with 3 microl of 8% wheat germ agglutinin-horseradish peroxidase in the left nodose ganglion. The nodose ganglia, the stomach, the first 8 cm of duodenum, and the cecum were prepared as wholemounts and were processed with tetramethyl benzidine. Hepatic afferent innervation of the ventral stomach consisted of one or more bundles entering at the lower esophageal sphincter and coursing to the forestomach, where they branched into distinct terminal fields. The only fibers on the dorsal forestomach were distal branches and terminals that wrapped around the greater curvature from the ventral side. Hepatic afferents supplied the forestomach with both intraganglionic laminar endings (IGLEs; putative mechanosensors that coordinate peristalsis) and intramuscular arrays (IMAs; considered tension receptors). IGLEs were located primarily on the ventral wall of the stomach, whereas IMAs were distributed symmetrically. Afferents were also supplied to the distal antrum and the pylorus, with pyloric innervation consisting almost exclusively of IMAs. Innervation of the proximal duodenum was denser in the first 3 cm and decreased progressively caudally, with only meager innervation after 6 cm. Cecal innervation consisted of a few fibers at the ileocecal junction. Duodenal and cecal endings were predominately IGLEs. These results indicate that the hepatic branch carries sensory information from the forestomach, antrum, pylorus, duodenum, and cecum. Furthermore, the different terminals it supplies suggest that the branch mediates a multiplicity of gastrointestinal functions.
Afferent Pathways↗
The RecB protein of Escherichia coli translocates along single-stranded DNA in the 3' to 5' direction: a proposed ratchet mechanism.
To investigate the role that the individual subunits play in the ATP-dependent helicase activity of the RecBCD protein we have investigated the ability of the RecB, RecC and RecD proteins to displace various 20-mer oligonucleotides annealed to either end or to the centre of an oligonucleotide 60 bases long. The results show that the only subunit which can displace the 20-mers in the absence of the other subunits is the RecB protein. Moreover, the 20-mer is displaced only if it is annealed to the 60-mer at the 5' end or the middle, suggesting that the RecB protein translocates along the 60-mer in the 3' to 5' direction, displacing annealed 20-mers as it proceeds. We have shown that reconstituted RecBC and RecBCD complexes displace the 20-mers but, unlike RecB, they do not require a 3'-ended single-stranded region for helicase action, but can displace the 20-mers from either end of the 60-mer. The level of helicase activity of the RecBC complex is considerably greater than that of RecB alone, and the activity of the RecBCD complex appears to be greater still. This hierarchy of activity is also shown by DNA binding studies, but is not reflected in the ATPase activities of the enzymes. We have also shown that the ability of trypsin to cleave various sites on the RecB molecule is modified by the presence of ATP or ATP-gamma-S, suggesting that conformational changes may be induced in RecB upon ATP binding. We discuss a model for the ATP-driven, unidirectional motion of the RecB translocase along single-stranded DNA. In this model, the RecB molecule binds to single-stranded DNA and then translocates along it, one base at a time, in the 3' to 5' direction, by a 'ratchet' mechanism in which repeated stretching and contraction of the protein is coupled to ATP hydrolysis. The RecC protein in the RecBC complex is proposed to act as a 'sliding clamp' which increases processivity by preventing dissociation.
Amino Acid Sequence↗
Regulation of IkappaB beta in WEHI 231 mature B cells.
Constitutive activation of NF-kappaB in WEHI 231 early mature B cells resembles the persistent activation of NF-kappaB that is observed upon prolonged stimulation of other cells. In both cases, NF-kappaB DNA binding complexes are found in the nucleus, despite the abundance of cytosolic IkappaB alpha. Recently, we have shown that prolonged activation of 70Z/3 cells with lipopolysaccharide results in the degradation of IkappaB beta, followed by its subsequent resynthesis as a hypophosphorylated protein. This protein was shown to facilitate transport of a portion of NF-kappaB to the nucleus in a manner that protects it from cytosolic IkappaB alpha. We now demonstrate that the most abundant form of IkappaB beta in WEHI 231 cells is a hypophosphorylated protein. This hypophosphorylated IkappaB beta is found in a stable complex with NF-kappaB in the cytosol and is also detected in NF-kappaB DNA binding complexes in the nucleus. It is likely that hypophosphorylated IkappaB beta in WEHI 231 cells also protects NF-kappaB from IkappaB alpha, thus leading to the continuous nuclear import of this transcription factor.
Acetylcysteine↗
Design sequence and mouth preparation for the removable partial denture.
This article discusses the procedure for designing the "best" removable partial denture. The best design will preserve the abutment teeth and the edentulous ridge. The restorative dentist's task in making an RPD is not to try to maintain function as it had been prior to tooth loss but rather to preserve what remains of the oral mechanism.
Denture Bases↗
Physical, sexual and emotional violence against women: a general practice-based prevalence study.
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Adolescent↗
Duodenogastric reflux of intestinal infusions in rats is volume dependent.
Experiments employing infusions of nutrients into the gastrointestinal tract commonly deliver large volumes of solutions without evaluating the possibility that reflux of the infusate to more orad sites may occur. To assess this possibility for one conventional paradigm, rats with gastric fistulas and intestinal catheters were infused intraduodenally (4.0 to 5.0 cm distal to pylorus) in association with a meal. Infusions of 0.0 ml to 15.0 ml of 3% glucose and a dye marker or 0.9% saline containing a dye marker were delivered at 1 ml/min, and stomach contents were assayed for the infusates. All three probes were detected in stomach contents. The glucose marker proved the most sensitive of the three and indicated that duodenogastric reflux occurred in a dose-dependent manner with infusions > 2.5 ml.
Animals↗
Identification of a novel NF-kappaB p50-related protein in B lymphocytes.
In most cell types other than mature B lymphocytes and macrophages, the transcription factor NF-kappaB remains in an inactive form in the cytosol by being bound to the inhibitory proteins IkappaBalpha and IkappaBbeta. To investigate the regulation of constitutively active NF-kappaB in B lymphocytes, we have examined the composition of Rel protein complexes in different mouse B-cell lines. As reported previously, the constitutively active complex in mature B cells was predominantly p50:c-Rel. However, the kappaB binding complex in the plasmacytomas that were examined lacked c-Rel and instead contained only a p50-related protein. This p50-related protein (p55) cross-reacts with three different p50 antisera, exists in both the cytosol and the nucleus, and is the protein that binds to kappaB sites in plasma cells. Transfection of reporter constructs into plasma cells indicates that the p55 complex is also transcriptionally active. The p55 protein can be detected in splenocytes from mice lacking the p105/p50 gene, and therefore it appears to be the product of a distinct gene. The implications of the existence of a NF-kappaB p50-related protein in plasma cells that is capable of binding to kappaB sites and activating transcription are discussed.
Animals↗
Gastric volume rather than nutrient content inhibits food intake.
To evaluate the separate contributions of distension and nutrient stimulation of the stomach to the inhibition of short-term food intake and, particularly, to reassess previous analyses based on the inflatable gastrointestinal cuff, four experiments were performed. Rats equipped with pyloric cuffs and indwelling gastric catheters consumed a liquid diet ad libitum. Their consumption during short-term (30 min) feeding bout was measured after gastric infusions on cuff-open and cuff-closed trials. Animals taking meals (approximately 5 ml) with cuffs closed immediately after receiving intragastric infusions of 2.5, 5, 7.5, or 10 ml of normal saline exhibited both suppression at the smallest infusion and a dose-dependent reduction across the other volumes (experiment 1). Additionally, when the test diet concentration was varied, animals with their cuffs closed consumed a constant volume, not a constant number of calories (experiment 2). Furthermore, cuff-closed animals exhibited no more suppression to 5-ml intragastric infusions of nutrients (including, on different trials, 50 and 100% Isocal diet; 10, 20, and 40% glucose; and 40% sucrose and 40% fructose) than to the same volume of saline (experiments 3 and 4). In contrast, on cuff-open trials in which gastric contents could empty into the duodenum, these same nutrient loads were more effective (except fructose) than saline in producing suppression of food intake. In summary, although both limited gastric distension with the pylorus occluded and intestinal nutrient stimulation with the cuff open effectively reduced intake, cuff-closed gastric loads of mixed macronutrients or carbohydrate solutions of 2-8 kcal, pH from 5.8 to 6.7, and osmolarities between 117 and 2,294 mosM/kg produced only the distension-based suppression generated by the same volume of saline.
Animal Nutritional Physiological Phenomena↗
QARNNS recollections: nor the years condemn.
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History, 20th Century↗
I kappa B-beta regulates the persistent response in a biphasic activation of NF-kappa B.
We have cloned the cDNA encoding I kappa B-beta, one of the two major I kappa B isoforms in mammalian cells. The recombinant I kappa B- beta protein interacts with equal affinity to p65 and c-Rel and does not exhibit a preference between these Rel proteins. Instead the primary difference between I kapp B-alpha and I kappa B-beta is in their response to different inducers of NF-kappa B activity. One class of inducers causes rapid but transient activation of NF-kappa B by primarily affecting I kappa B-alpha complexes, whereas another class of inducers causes persistent activation of NF-kapa B by affecting both I kappa B-alpha and I kappa B-beta complexes. Therefore, the overall activation of NF-kappa B consists of two overlapping phases, a transient phase mediated through I kappa B-alpha and a persistent phase mediated through I kappa B-beta.
Amino Acid Sequence↗
Junctional epidermolysis bullosa and pyloric atresia: a distinct entity. Clinical and pathological studies in five patients.
Junctional epidermolysis bullosa (JEB) associated with pyloric atresia (PA) is a distinct entity which is inherited as an autosomal recessive disorder. We describe five patients with this association; four died in the neonatal period and one is still alive at 4 years of age. The cutaneous lesions in these patients are identical or similar to those in other JEB subtypes. Urinary tract involvement is part of the syndrome and presents a problem for long-term survival. Using the monoclonal antibody GB3 we investigated skin biopsies from three of our patients and showed normal expression in all of them, unrelated to the outcome of their disease. This indicates that the GB3 monoclonal antibody is without prognostic significance in this syndrome. It is clear that JEB with PA is a distinct entity. The molecular basis as yet is unknown.
Antigens, Surface↗
Selective vagal rhizotomies: a new dorsal surgical approach used for intestinal deafferentations.
We have developed a dorsal intracranial surgery that is minimally invasive and gives excellent access to either afferent or efferent vagal rootlets to produce selective deafferentations or deefferentations in the rat. We have combined this new unilateral afferent rhizotomy with a contralateral celiac branch cut (to completely deafferent the intestines) and a duodenal catheter placement 4 cm distal to the pylorus. Animals were maintained with 17 h/day access to a nutritionally complete liquid diet. Measures of first meal size, daily intake, and body weight before and after both surgeries indicated that animals with unilateral vagal deafferentiations recovered as fast and completely as sham-operated controls. Intraduodenal oleate (1.2 kcal) infusions reduced the size of the first meal in surgical controls (by 64%; P < 0.01) but not in the deafferented rats. A dual wheat germ agglutinin-horseradish peroxidase/Fluorogold protocol provides verification of sensory and motor lesions. The selective vagal deafferentation provided by the new surgery offers a useful model for determining gastrointestinal sites of nutrient detection and separating pre- and postabsorptive consequences of a meal.
Afferent Pathways↗