'The elusive concept of "Internal Objects" (1934-1943)' by R. D. Hinshelwood.
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Computer Communication Networks↗
Biomedical subjects
P Williams
Publications and source records attributed to P Williams.
'Thick- and thin-skinned organisations and enactment in borderline and narcissistic disorders' by Anthony W. Bateman.
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Acting Out↗
Interleukin 6 and interferon-gamma gene expression in lung transplant recipients with refractory acute cellular rejection: implications for monitoring and inhibition by treatment with aerosolized cyclosporine.
BACKGROUND: The purpose of this study was to correlate cytokine gene expression from bronchoalveolar lavage (BAL) cells and peripheral blood lymphocytes (PBL) with graft histology in recipients with persistent acute rejection treated with aerosolized cyclosporine (ACsA). METHODS: We measured mRNA for interleukin (IL) 6, interferon (IFN)-gamma, and IL-10 in recipients (1) without rejection (n=13), (2) with acute rejection that responded to pulsed methylprednisolone (n=7), and (3) with "refractory" acute rejection that failed to respond to conventional immunosuppression (n=17). In the latter group, ACsA was initiated. RESULTS: BAL cell IL-6 and IFN-gamma were highest in recipients with refractory rejection compared with recipients with steroid-responsive rejection and recipients with no rejection. Improvement in rejection histology occurred in 15 of 17 recipients who were treated with ACsA. IL-6 and IFN-gamma mRNA levels from BAL cells decreased during treatment with ACsA (median IL-6:actin ratio: before treatment, 0.40 vs. after treatment, 0.003, P=0.001; IFN-gamma:actin ratio: before treatment, 0.32 vs. after treatment, 0.04, P=0.001). PBL IL-6 and IFN-gamma mRNA expression also decreased during ACsA treatment after 180 days. Expression of IL-10 mRNA from BAL and PBL did not change during ACsA treatment (0.0 vs. 0.03 and 0.0 vs. 0.02, respectively). CONCLUSIONS: IL-6 and IFN-gamma mRNA expression from BAL cells was highest in those recipients with refractory histologic acute rejection. ACsA was associated with decreased IFN-gamma and IL-6 gene expression in BAL cells and PBL.
Acute Disease↗
Mice with genetic gamma-glutamyl transpeptidase deficiency exhibit glutathionuria, severe growth failure, reduced life spans, and infertility.
A mouse mutant with glutathionuria was discovered by screening for amino acidurias in the progeny of ethylnitrosourea-mutagenized mice. Total glutathione concentration was increased in both blood and urine but decreased in liver homogenates from affected mice. Glutathionuric mice exhibited lethargy, severe growth failure, shortened life spans and infertility. gamma-Glutamyl transpeptidase activity was deficient in kidney homogenates of glutathionuric mice. The glutathionuric phenotype in these mice is inherited as an autosomal recessive trait. This mouse mutant will be a useful animal model for the study of gamma-glutamyl transpeptidase physiology and glutathione metabolism.
Animals↗
Elemental iron does repress transferrin, haemopexin and haemoglobin receptor expression in Haemophilus influenzae.
The iron repressible nature of Haemophilus influenzae transferrin binding proteins suggests a regulatory role for elemental iron in their expression. The existence of a Haemophilus ferric uptake repressor (Fur) binding motif identified in the promoter region of both tbpA and tbpB further supports this hypothesis. However, a recent study using brain heart infusion growth medium suggested that transferrin binding protein synthesis in H. influenzae was haem-rather than iron-regulated. The present study re-investigates this observation and using a chemically defined medium, we demonstrate that elemental iron haem or protoporphyrin IX can each regulate Haemophilus influenzae transferrin, haemopexin and haemoglobin receptor expression.
Carrier Proteins↗
Dissection of the promoter/operator region and evaluation of N-acylhomoserine lactone mediated transcriptional regulation of elastase expression in Pseudomonas aeruginosa.
In Pseudomonas aeruginosa, expression of the lasB gene which codes for the metalloprotease, elastase, depends on small diffusible N-acylhomoserine lactones. lasB expression is regulated through the interactions of N-3-oxododecanoyl-L-homoserine lactone and N-butanoyl-L-homoserine lactone with the transcriptional activators LasR and VsmR(RhlR), respectively. To investigate lasB expression further, we first located the transcriptional start site to a position 141 bp upstream from the translational start site. Using this information, we constructed a series of plasmids containing consecutive 5' deletions of the upstream region of lasB fused to a promoterless chloramphenicol acetyltransferase reporter gene. The results obtained indicate that three regions are required for efficient transcription of lasB; a 35 bp palindromic sequence located at +26 to +60 bp upstream from the translation start site, and two regions located upstream of the transcription start site, at -135 to -85 bp and -63 to -26 bp, respectively. Deletion of the latter region results in the loss of both N-butanoyl-L-homoserine lactone- and N-3-oxododecanoyl-L-homoserine lactone-mediated stimulation of lasB expression and provides further support for the role of this operator site as a target for either or both LasR and VsmR.
Bacterial Proteins↗
Rhamnogalacturonan II, a dominant polysaccharide in juices produced by enzymic liquefaction of fruits and vegetables.
Rhamnogalacturonan II (RG-II), a small complex pectic polysaccharide, is released from apple (Malus domestica), carrot (Daucus carota), and tomato (Solanum lycopersicum) by treatment with two commercial liquefying enzyme preparations. RG-II was isolated by size-exclusion chromatography from apple, tomato, and carrot juices obtained by enzymic liquefaction. All the RG-IIs contained the diagnostic sugars, apiose, 2-O-methyl-L-fucose, 2-O-methyl-D-xylose, aceric acid, Kdo and Dha. Glycosyl-linkage compositions of the neutral and acidic sugars, including aceric acid, were consistent with the hypothetical model described for sycamore RG-II confirming the conservation of RG-II in plants. Thus, when pectinolytic enzyme preparations are used to process fruits and vegetables, RG-II is released as a main soluble polysaccharide fraction while other pectic polysaccharides are heavily degraded.
Carbohydrate Conformation↗
BIA/MS: interfacing biomolecular interaction analysis with mass spectrometry.
Biomolecular interaction analysis (BIA) which utilizes surface plasmon resonance (SPR) detection of affinity-captured analytes has been interfaced with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI). Femtomole quantities of a peptide, myotoxin a, were detected by direct MALDI analysis of sensor chips used during BIA of a polyclonal anti-myotoxin a IgG/myotoxin a system. Further, different interactive surfaces (flow cells) present on a single biosensor were targeted individually for mass spectrometric analysis. System compatibility of the combined approach was demonstrated with sensitivities, detection limits, and analytical performances comparable to those intrinsic to the individual analyses. The combined approach unites the real-time capabilities of SPR-based BIA with the qualitative specificity of mass spectrometry.
Biosensing Techniques↗
Therapeutic ERCP: a cost-prohibitive procedure?
BACKGROUND: ERCP is increasingly being performed for therapeutic purposes and engenders a proliferation of disposable equipment without a clear indication of cost-effectiveness. METHODS: We analyzed the financial impact of ERCP by prospectively analyzing ERCPs performed in our institution from June 1, 1994, to September 30, 1994, by calculating charges related to indirect costs, disposable equipment costs, and overall reimbursement. The data were analyzed according to insurance payor as well. RESULTS: Disposable equipment costs a mean of $149 per diagnostic ERCP and $532 per therapeutic ERCP. For diagnostic ERCP, disposable equipment accounted for 27% of reimbursement; for therapeutic ERCP, disposable equipment accounted for 68% of reimbursement. Although overall reimbursement was higher for therapeutic ERCP, the very high direct costs related to disposable equipment limited the ability of reimbursement to cover indirect costs. CONCLUSIONS: Depending on the complexity of cases, quantity of disposable equipment used, and patient-insurance mix, therapeutic ERCP may be cost prohibitive for a given endoscopy unit. Indirect costs should be more carefully and quantitatively analyzed. Disposable equipment should be evaluated in terms of cost, safety, and patient outcome.
Cholangiopancreatography, Endoscopic Retrograde↗
Control of Legionella in a hospital potable water supply.
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Chlorine↗
Characterization of renal ischemia-reperfusion injury in rats.
The purpose of this study was to characterize the time course of renal ischemia-reperfusion injury in the rat. Male Sprague-Dawley rats were subjected to bilateral renal clamping for 45 min. At reestablishment of blood flow, the rats were divided into nine groups (representing 0, 0.5, 1, 2, 4, 6, 9, and 24 h, and 1 week post-ischemia). At each time point, blood samples were taken for analysis of blood urea nitrogen (BUN) and creatinine, and both kidneys were harvested for histopathology and myeloperoxidase activity (MPO) assays. An intracellular adhesion molecular (ICAM-1) monoclonal antibody (IMAb) was tested in a separate group of animals (1 mg/rat) to confirm that it may provide renal protection previously reported by Kelly et al. (1994). Following renal ischemia, significant increases in serum BUN and creatinine were observed compared to levels in normal animals. Serum BUN and creatinine increased 2, 4, and 6 h post-ischemia leading to peak elevations 24 h post-ischemia. Values returned to normal at the 1 week time point. MPO activity was slightly increased 2 and 4 h following ischemia, with peak elevations occurring at the 6-h and 9-h time points. Histopathologic examination of kidneys revealed that the most severe damage occurred at the 24-h time point, which correlated with the peak elevations in serum BUN and creatinine. Evidence of renal injury was still evident histologically 1 week following ischemia, although renal function tests (BUN and creatinine) had returned to normal. In summary, renal injury following ischemia may be demonstrated as early as 4 h post-ischemia as judged by changes in renal function, MPO levels, and renal histopathology. However, based upon renal function tests and histology, peak injury is observed approximately 24 h following ischemia. The ICAM-1 monoclonal antibody, ICAM-Ab, provided some renal protection against ischemia-reperfusion injury in this study as measured by serum creatinine, BUN and renal histopathology. However, in contrast to the results reported by Kelly et al., the magnitude of the protective effects was not as dramatic in the present study, and furthermore, no reductions in renal MPO activity were observed.
Animals↗
Season of birth: aetiological implications for epilepsy.
In most cases of epilepsy it is not possible to reach an aetiological diagnosis. Recent research points to a pre-perinatal disruption of the neurodevelopment as being the cause of at least some of these epilepsies of unknown aetiology. The object of this study was to corroborate this hypothesis from an epidemiological perspective and identify the most likely candidates for causes of this damage. The approach used was an analysis of the seasonal pattern of births in a large sample of epileptic patients discharged from NHS hospitals in England and Wales. The results illustrated that the seasonality of the births in the epileptic sample was significantly different from that of the general population, with an excess of patients born in December and January and a deficit of those born in September. This "seasonality' was present only in the patients born before the late 1950s. These results are suggestive of the existence of an aetiological factor for epilepsy with a seasonal presence in the environment and which is epileptogenic when acting in the pre-perinatal period. Prenatal infections, obstetric complications and nutrititional deficiencies are amongst the hypotheses developed on the nature of this agent(s).
Adolescent↗
Comparison of carprofen and flunixin meglumine as adjunctive therapy in bovine respiratory disease.
In an open, controlled, multi-centre clinical field trial, seven 'naturally occurring' outbreaks of acute febrile (rectal temperature > or = 39.5 degrees C) respiratory disease in housed calves were treated with a single antimicrobial agent, and either the non-steroidal anti-inflammatory drug (NSAID) carprofen (n = 95) or flunixin meglumine (n = 92) on an alternate basis. Carprofen was administered as a single subcutaneous injection at a mean dosage of 1.4 mg kg-1 (range 1.2 to 1.9 mg kg-1) body weight on the first day and flunixin meglumine by intravenous injection at a mean dosage of 2.0 mg kg-1 (range 1.2 to 2.6 mg kg-1) body weight on the first 3 consecutive days. All calves were examined clinically immediately prior to initial treatment and on three occasions up to 1 week after the end of treatment. There were no statically significant differences between NSAID groups in reduction of clinical parameters between examinations, or in overall efficacy. This trial demonstrated that a single dose of carprofen was equally effective as three daily doses of flunixin meglumine as adjunctive therapy to antimicrobial treatment in acute respiratory disease in calves.
Animals↗
Structural processing and implicit memory for possible and impossible figures.
Previous investigations have shown that participants are biased to respond "possible" to studied items when asked to decide whether objects could or could not exist in an object possibility test. The present study clarified and extended the concept of bias in implicit memory research in two ways. First, the authors showed that participants were biased to respond "possible" (rather than "impossible") on the object possibility test because structural processing was facilitated by prior study of possible, but not impossible, portions of objects. Second, the authors demonstrated that bias in this context was a form of, not an alternative to, implicit memory, by showing priming effects in response times when accuracy scores for studied and unstudied items were equated. The authors concluded by comparing proceduralist and memory-systems accounts of implicit memory effects and suggested that the two approaches could be seen as complementary rather than conflicting.
Humans↗
Strength in the lower limbs, visual contrast sensitivity, and simple reaction time predict cognition in older women.
The authors investigated the association between sensorimotor variables indicative of biological aging and cognition. A community sample of 202 women ages 60-86 was assessed on 5 measures of lower limb strength, visual contrast sensitivity (VisCS), and reaction time (RT). Hierarchical multiple regression revealed that the sensorimotor variables explained age-related variance in measures of reasoning and total variance in measures of reasoning after education, health, mood, and physical activity were controlled for. It is concluded that in addition to better known predictors of cognitive aging, such as RT and VisCS, lower limb strength is an important predictor of performance on cognitive tests.
Aged↗
A novel regulatory system required for pathogenicity of Xanthomonas campestris is mediated by a small diffusible signal molecule.
Mutations in the seven clustered rpf genes cause downregulated synthesis of extracellular enzymes and reduced virulence of Xanthomonas campestris pathovar campestris (Xcc). The phenotype of mutants in one of the genes, rpfF, can be restored by a diffusible extracellular factor (DSF) produced by all Xcc strains tested, apart from rpfF and rpfB mutants. DSF accumulates in early stationary phase (when synthesis of enzymes is maximal), but levels decline subsequently. Addition of DSF to exponentially-growing wild-type bacteria does not cause precocious enzyme synthesis. rpfB and rpfF are expressed throughout growth, but the rate increases in early stationary phase. RpfB is predicted to be a long-chain fatty acyl CoA ligase, and RpfF shows some relatedness to enoyl CoA hydratases. The properties of DSF suggest that it may be a fatty-acid derivative, and certain lipid preparations possess DSF activity at higher concentrations. These include lipid extracts and acid-hydrolysed lipoplysaccharide and lipid A from Xcc, and purified dodecanoic and hydroxydodecanoic acid. DSF production is confined to certain xanthomonads. We propose a model for the DSF system, which represents a novel mechanism for regulating virulence factor synthesis in response to physiological or environmental changes.
Diffusion↗
Regulation of the xcp secretion pathway by multiple quorum-sensing modulons in Pseudomonas aeruginosa.
The virulence of the opportunistic pathogen Pseudomonas aeruginosa is largely dependent upon the extracellular production of a number of secreted proteins with toxic or degradative activities. The synthesis of several exoenzymes is controlled in a cell-density-dependent manner by two interlinked quorum-sensing systems. Their secretion across the outer membrane occurs through the Xcp translocation machinery. The xcp locus located at 40 min on the chromosome consists of two divergently transcribed operons, namely xcpPQ and xcpR to xcpZ. In this study, transcriptional fusions were constructed between the xcpP and xcpR genes and the lacZ reporter. Transcriptional activation of the xcpP and xcpR genes in P. aeruginosa is growth-phase dependent and the lasR-lasI autoinduction system is required for this control. In the heterologous host Escherichia coli, the lasR gene product, together with its cognate autoinducer N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), activates both the xcpP-lacZ and the xcpR-lacZ gene fusion. The second P. aeruginosa quorum-sensing modulon rhIR-rhII (vsmR-vsmI) is also involved in the control of the xcp genes. Expression of the lacZ fusions is strongly reduced in PANO67, a pleiotropic mutant defective in the production of N-acyl-homoserine lactones responsible for the activation of RhIR. Furthermore, introduction of the lasR mutation in PANO67 results in additional diminution of xcpR transcription, indicating that the two systems can regulate their target genes independently. These data demonstrate that expression of the xcp secretion system depends on a complex regulatory network involving cell-cell signalling which controls production and secretion of virulence-associated factors.
Bacterial Proteins↗
The rap and hor proteins of Erwinia, Serratia and Yersinia: a novel subgroup in a growing superfamily of proteins regulating diverse physiological processes in bacterial pathogens.
The enteric bacterium Serratia marcescens is an opportunistic human pathogen. The strain ATCC39006 makes the red pigment, prodigiosin (Pig), and the beta-lactam antibiotic carbapenem (Car). Mutants were isolated that were concomitantly defective for Pig and Car production. These mutants were found to have a mutation in the rap gene (Regulation of Antibiotic and Pigment). Sequence analysis of the rap gene revealed a predicted protein product showing strong homology to SlyA, originally thought to be a haemolytic virulence determinant in Salmonella typhimurium. Homologues of rap were detected in several bacterial genera, including Salmonella, Yersinia, Enterobacter, and species of the plant pathogen, Erwinia. The Erwinia hoeEr (homologue of rap) and the Yersinia horYe genes were also found to be very similar to rap and slyA. Marker exchange mutagenesis of horEr revealed that it encoded a regulatory protein controlling the production of antibiotic and exoenzyme virulence determinants in the phytopathogen, Erwinia carotovora subspecies carotovora. We have shown that these new homologues of SlyA form a highly conserved subgroup of a growing superfamily of bacterial regulatory proteins controlling diverse physiological processes in human, animal and plant pathogens.
Amino Acid Sequence↗