The evolution of haematopoietic cytokine/receptor complexes.

The evolutionary expansion of the haematopoietic cytokines and their receptors is characterized by the duplication of both cytokines and receptors. A systematic analysis of primary sequence homology indicates that receptors for gp130-associated cytokines group into signal transducing and non-signal transducing receptors. This observation is consistent with the evolution of the interleukins 6, 11 and 12, granulocyte colony stimulating factor (G-CSF), leukemia inhibitory factor (LIF), oncostatin M, and the ciliary neurotrophic factor complexes from a common ancestral complex which included a homodimer of gp130-like signalling receptors and an interleukin 6 receptor-like non-signalling receptor.

Estimating the magnitude of carcinogenic effects in long-term animal studies.

Carcinogenicity studies seek to compare the incidence of tumours in animals exposed to the substance under investigation and animals used as controls. The conventional method of analysis is the Peto test, which assumes that tumours are either instantly fatal or have no effect on mortality and requires a judgement to be made regarding the lethality of each tumour. Such an assumption seems unrealistic and the judgement is often difficult to make and unreliable.

Design of a placebo-controlled clinical trial of long-acting diltiazem and aspirin versus aspirin alone in patients receiving thrombolysis with a first acute myocardial infarction. Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis Post-Thrombolysis (diltiazem) (INTERCEPT) Research Group.

Several pharmacologic forms of adjunctive therapy, designed to enhance the efficacy of thrombolysis following acute myocardial infarction (AMI), are being explored. However, few studies have assessed the use of standard secondary prevention therapies (beta-blockers, angiotensin-converting enzyme inhibitors, magnesium, calcium antagonists, etc.) for antecedent thrombolysis.

Reducing animal numbers in the fixed-dose procedure.

The fixed-dose procedure (FDP) was proposed by the British Toxicology Society (1984) as an alternative to assessment of acute oral toxicity via estimation of the LD50. The procedure is incorporated in OECD guidelines on acute oral toxicity testing. Whitehead and Curnow (1992) used a mathematical model to describe the statistical properties of the FDP.

S-adenosyl-L-homocysteine hydrolase from Xenopus laevis--identification, developmental expression and evolution.

S-Adenosyl-L-homocysteine hydrolase (EC 3.3.1.

Identification and characterization of a cDNA encoding ribosomal protein S12 from Xenopus laevis.

The complete nucleotide (nt) sequence of the cDNA clone XL-S12, encoding a Xenopus laevis (Xl) homologue of the mammalian ribosomal protein S12, has been determined. The sequence predicts a Xl S12 protein of 132 amino acids (aa) with a molecular mass of 14.7 kDa.

A meta-analysis of clinical trials involving different classifications of response into ordered categories.

Statistical methods are available for performing a meta-analysis when the response variable of interest is the same in each study. Problems arise when studies exploring a common therapeutic question use different patient response types. This article presents statistical methods for combining studies which involve different classifications of response into ordered categories.

Contamination of hands and work surfaces with Salmonella enteritidis PT4 during the preparation of egg dishes.

Salmonella enteritidis PT4 was recovered from fingers following the breaking of intact shell eggs artificially contaminated in the contents with the bacterium. Kitchen utensils used to mix egg dishes were salmonella-positive, sometimes after washing. Following the preparation of batter or the mixing of eggs, S.

Organization of the region encompassing the human serum amyloid A (SAA) gene family on chromosome 11p15.1.

The four members of the human serum amyloid A protein (SAA) gene family are clustered on human chromosome 11p15.1. Three genes are differentially expressed and encode small apolipoproteins of M(r) 12-19 kDa: SAA1 and SAA2 encode the acute phase SAAs (A-SAAs), and SAA4 encodes the constitutively expressed SAA (C-SAA).

Resistance to secondary amyloidosis in A/J mice is not significantly associated with allelic variants linked to the serum amyloid A gene cluster.

We have tested the hypothesis that structural allelic variants of serum amyloid A confer relative resistance to secondary amyloidosis in the A/J mouse. F2 mice, previously generated from amyloid-resistant (A/J) and amyloid-susceptible (C57BL/6J) strains and categorized with respect to amyloid susceptibility, were genotyped by polymerase chain reaction (PCR) amplification of the polymorphic D7Nds5 microsatellite. This microsatellite is closely linked to the SAA gene cluster and can discriminate between D7Nds5 alleles of A/J and C57BL/6J origin.

Characterization, expression and evolution of mouse beta 2-glycoprotein I (apolipoprotein H).

beta 2-glycoprotein I (beta 2I) is a 50kDa serum glycoprotein of ill defined function. Based upon its capacity to bind negatively charged phospholipids a number of possible inhibitory roles for beta 2I have been proposed. We have cloned and sequenced a full length mouse beta 2I cDNA clone and demonstrated that mouse beta 2I does not behave as an acute phase reactant following an experimentally induced inflammation.

The putative fifth human serum amyloid A protein (SAA)-related gene "SAA5" is defined by SAA3.

The four well characterised members of the human serum amyloid A protein (SAA) gene family are clustered on chromosome 11p15.1. The acute phase SAA genes, SAA1 and SAA2, are hyperinducible in response to inflammatory stimuli, whereas SAA4 is only minimally induced, and SAA3 is a pseudogene.

The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein.

Following an acute phase stimulus, such as infection or physical injury, many liver-derived plasma proteins are increased in concentration. These provide enhanced protection against invading micro-organisms, limit tissue damage and promote a rapid return to homeostasis. Diana Steel and Alexander Whitehead discuss the gene structure, regulation and possible clinical significance of the most dramatically induced acute phase reactants.

Evolution of the serum amyloid A (SAA) protein superfamily.

The serum amyloid A (SAA) superfamily comprises a number of genes and proteins characterized from a range of mammalian species. The majority of members described to date are dramatically induced during the acute-phase response, suggesting an important short-term beneficial role in the response to tissue injury and inflammation. However, important disease associations have also been proposed for certain SAAs during chronic inflammation.

The human serum amyloid A protein (SAA) superfamily gene cluster: mapping to chromosome 11p15.1 by physical and genetic linkage analysis.

The human serum amyloid A protein (SAA) family comprises a number of small, hepatically produced, differentially expressed apolipoproteins encoded by genes localized on the short arm of chromosome 11.SAA1 and SAA2 are highly related genes that together encode the acute-phase SAAs; SAA3 is a pseudogene; and SAA4 is a low-level constitutively expressed gene encoding constitutive SAA. We have used a combination of physical and genetic mapping techniques to provide evidence that the SAA gene superfamily comprises a cluster of closely linked genes localized to 11p15.

The mouse interleukin 1 receptor antagonist protein: gene structure and regulation in vitro.

The interleukin 1 receptor antagonist (IL-1ra) protein is an inhibitor of the pro-inflammatory cytokine interleukin 1. We have sequenced the mouse gene encoding the monocyte form of IL-1ra (IL-1rn) and compared it with the sequence of the human homologue. In addition to high levels of similarity between the coding regions of the two genes, portions of the introns show surprisingly high levels of identity.

Chemical emergencies and the Health Advisory Group on Chemical Contamination Incidents (HAGCCI).

The Health Advisory Group on Chemical Contamination Incidents (HAGCCI) (pronounced 'Hag-C'), is an independent advisory group which was established to advise Directors of Public Health throughout the United Kingdom (UK) and the Chief Medical Officers of the UK Health Departments on the medical aspects of major chemical contamination incidents involving air, soil or water. Separate arrangements exist for the provision of advice on chemical contamination of food. HAGCCI comprises a core group of three individuals, supported by a multidisciplinary panel of experts, and a secretariat provided by the Department of Health.

Egg age and the growth of Salmonella enteritidis PT4 in egg contents.

The growth of Salmonella enteritidis PT4 in albumen around an intact yolk was governed by the age of the egg on inoculation. In the majority of eggs, held at 20 degrees C, the bacterium was unable to grow rapidly until eggs had been stored for approximately 3 weeks. The multiplication of S.

Identification of a novel member of the pentraxin family in Xenopus laevis.

Pentraxins are a family of acute phase reactants. Two family members, C-reactive protein (CRP) and serum amyloid P component (SAP), are known in a range of mammalian species. CRP and SAP are both about 200 residues long, and arose from a gene duplication event, apparently before the divergence of the mammalian orders.

Development of a blood urea monitoring system for the closed loop control of dialysis.

Optimal hemodialysis prescription through real-time blood urea (BU) monitoring and closed loop control of urea removal would be of significant clinical value. Progress toward a bedside BU analyzer and a control system is described here. An Amicon Minifilter inserted into the arterial bloodline provides a 1 ml/min stream of protein free ultrafiltrate for analysis.

Localization of four human serum amyloid A (SAA) protein superfamily genes to chromosome 11p: characterization of a fifth SAA-related gene sequence.

The serum amyloid A proteins (SAAs) are heterogeneous differentially expressed apolipoproteins of M(r) 12-19 kDa. Four SAA loci have been described. Two of the loci (SAA1 and SAA2) encode acute-phase SAAs (A-SAAs), which exhibit a dramatic transient increase in serum concentration in response to inflammatory stimuli; a third locus (SAA3) defines a pseudogene; and a fourth locus (SAA4) encodes a constitutively expressed SAA (C-SAA).