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Comparison of the clinical and radiographic diagnosis of paediatric pneumonia.

Pneumonia causes 3.2 million deaths per year in children under 5 years old according to the World Health Organization. In spite of the number of deaths, no single clinical or radiological definition for the diagnosis of pneumonia is widely accepted. To determine the extent of agreement between clinical and radiographic diagnoses of pneumonia, we compared the clinical diagnoses made by an experienced paediatrician with diagnoses based on a paediatric radiologist's interpretation of chest radiographs. In 226 children with respiratory illness brought to a hospital outpatient department in Lesotho, pneumonia was the clinical diagnosis for 39 and the radiographic diagnosis for 40; however, for only 19 children did the 2 diagnoses concur. Children with a radiographic diagnosis of pneumonia tended to have been ill longer, to be older, and to be more likely to have a technically adequate radiograph than children with negative radiographs, independent of the clinical diagnosis. In this comparison, radiographic and clinical diagnoses for pneumonia differed substantially. Some of this discrepancy may be explained by misinterpretation of suboptimal films and different rates of evolution of radiographic and clinical manifestations of pneumonia. Radiographic studies and clinical evaluations produced complementary data in this evaluation: of the 60 children with clinical or radiographic evidence of pneumonia, 14 would not have been treated with an antimicrobial drug without radiography. Wider availability of radiography is needed to supplement clinical examination for the diagnosis of pneumonia, and may be particularly valuable in children more than 18 months old, those who have been ill for more than 6 d, and those with fever.

Female↗

Yeast histone H2A and H2B amino termini have interchangeable functions.

The N-terminal ends of histones H2B and H2A have very different sequences and rates of evolution. However, they both extend from the nucleosome core and are positively charged. Short sequences at the C termini of both proteins also differ from each other and appear to be hydrophilic. Deletions at the N and C termini of yeast histones H2B2 and H2A1 do not obviously affect the cell's viability under normal growth conditions. However, deletions at the N termini of both H2B and H2A in the same cell are lethal or result in greatly reduced viability. Even switching portions of the N termini between H2B and H2A to create two chimeric histone proteins within the same cell has no obvious effect on viability. This supports the argument that the N-terminal end of one protein complements the function of the other.

Amino Acid Sequence↗

Conservative system for dosage-dependent modulation of translational fidelity in eukaryotes.

Variations in dosage of some genes can alter the level of translational fidelity. The Saccharomyces cerevisiae genes that act as dosage-dependent suppressors and/or modulators of suppression, are the following: some tRNA genes (for example, tRNA(Gln)) inducing readthrough by mispairing; genes coding for either translational elongation factor or other proteins taking part in translation; and some genes of unknown function. We suggest that the SUP35 protein is a factor which may play a major role in balance-dependent regulation of translational fidelity. Homologues of this genes have been identified in other yeast genera (Pichia), green algae (Chlamydomonas) and various animals including man. No homologies have been found in the polychaeta (Nereis) or in insects (Drosophila). Rates of evolution differ for two separate parts of the genes; the N-terminal part, which is important for ambiguous translation in Saccharomyces, is markedly variable in the organisms tested. However, the C-terminal part which is required for yeast viability has a common origin but a separate evolution from that of the EF-Tu protein family.

Animals↗

Evidence that natural selection acts on silent mutation.

Analysis of nucleic acid sequence data of mammalian hemoglobin, yeast cytochrome c, and human interferon reveals strong biases in favor of specific codons. These biases do not appear to dissipate over time, suggesting that an indirect form of selection acts on silent mutations. The data are compatible with the "bootstrapping" hypothesis that silent mutations which alter the rate of evolution can hitchhike with traits whose appearance they facilitate. Selection involving modulating effects of codon usage on gene expression may also be involved, but the data appear to exclude simple maximization of gene expression.

Animals↗

Cloning and sequence analysis of the cDNA for the pituitary glycoprotein hormone alpha-subunit of the European eel.

A cDNA library constructed using mRNAs isolated from pituitary glands of estradiol-treated eels was screened with a cDNA fragment for the rat glycoprotein hormone alpha-subunit. Three out of 10,000 cDNA clones were revealed and subcloned in pUC13 for characterization and sequencing. All three had the same nucleotide sequence except for a single, silent change in the coding sequence for one of them, and for the location of the poly(A) tail. Analysis of the deduced amino acid sequence strongly suggests that these cDNA clones encode the precursor for the eel common glycoprotein hormone alpha-subunit. This precursor would therefore consist of a 93 amino acid apoprotein preceded by a 24 amino acid long signal peptide. Alignment with glycoprotein hormone alpha-subunits from fish and mammals reveals high homology, ranging from 60 to 90%. Particularly, the ten cysteines and the two putative N-linked glycosylation sites were at the same position. Comparison between fish and mammals shows also that two regions are highly conserved, comprising about half of the protein length. This high conservation rate through evolution argues for the importance of these regions in the conservation of biological properties of the alpha-subunits. In contrast, other regions are highly variable and could be responsible for the immunological specificity. Northern blot analysis of pituitary RNA from control and estradiol-treated eels showed that estradiol treatment strongly increases the pituitary content of mRNA encoding the glycoprotein hormone alpha-subunit.

Amino Acid Sequence↗

Cloning and characterisation of the rabbit growth hormone-encoding gene.

The gene encoding growth hormone (GH) has been cloned from a rabbit genomic library, and its sequence has been determined. The rabbit GH gene is similar to other mammalian GH, being comprised of five exons and four introns. As in rodents and artiodactyls, the rabbit GH occurs as a single gene, with no evidence for a cluster of GH-like genes, as is found in primates. The amino acid sequence of rabbit GH is similar to that of pig GH and other conserved mammalian GH, and, like these, differs markedly from the available sequences of ruminant and primate GH. This provides further support for the idea that, in mammals, GH show a slow underlying rate of evolution which has increased markedly on at least two occasions.

Amino Acid Sequence↗

Early spontaneous intermittent myocardial reperfusion during acute myocardial infarction is associated with augmented thrombogenic activity and less myocardial damage.

OBJECTIVES: This study investigated the influence of early spontaneous intermittent reperfusion on the extent of myocardial damage and its relation to endogenous hemostatic activity. BACKGROUND: In the early phase of acute myocardial infarction coronary occlusion is often intermittent, even before thrombolytic therapy is administered. The relation between this phenomenon, myocardial damage and hemostatic activity is unknown. METHODS: Holter ST segment recording and pretreatment plasma tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, prothrombin fragment F1 + 2 and soluble fibrin levels were measured in 57 patients with acute evolving myocardial infarction. Spontaneous intermittent myocardial reperfusion, defined as two or more episodes of transient resolution of ST segment elevation to within 0.05 mV of baseline, lasting > or = 1 min, before the start of recombinant t-PA (rt-PA) treatment was present in 28 patients (group 1) and absent in 29 (group 2). Left ventriculography and coronary angiography were performed 90 min after intravenous rt-PA administration. Plasma creatine kinase-MB fraction (CK-MB) levels were measured every 6 h for 24 h, and C-reactive protein levels were measured daily for 3 days. RESULTS: Group 1 had lower peak plasma CK-MB (141.9 +/- 28.3 vs. 203.8 +/- 23.3 IU/liter [mean +/- SEM], p < 0.014) and C-reactive protein levels (16 +/- 4 vs. 28 +/- 4 mg/liter on day 1; 26.6 +/- 5.5 vs. 61.8 +/- 14.4 mg/liter on day 2; 19.6 +/- 4.2 vs. 40.6 +/- 6.5 mg/liter on day 3, p < 0.012) and a higher left ventricular ejection fraction (62.9 +/- 4% vs. 51.1 +/- 5%, p < 0.04) than group 2. Group 1 had lower plasma t-PA antigen levels (15.6 vs. 27 micrograms/liter, p < 0.006) but higher prothrombin fragment F1 + 2 (1.8 vs. 1.1 nmol/liter, p < 0.003) and soluble fibrin levels (66.8 vs. 31 nmol/liter, p < 0.01). Coronary patency at 90 min was similar. CONCLUSIONS: Early spontaneous intermittent reperfusion during acute myocardial infarction is associated with augmented thrombogenic activity and less subsequent myocardial damage. This finding is consistent with a protective effect of intermittency on the myocardium and a procoagulant effect of spontaneous lysis on blood. It may also reflect a different rate of evolution of coronary thrombosis and myocardial infarction in patients with and those without spontaneous intermittent myocardial reperfusion.

Analysis of Variance↗

Direct sequencing of the activation peptide and the catalytic domain of the factor IX gene in six species.

By means of RNA amplification with transcript sequencing (RAWTS) under low stringency conditions, sequence was obtained directly without cloning for the activation peptide and the catalytic domain of factor IX from six species--sheep, pig, rabbit, guinea pig, rat, and mouse. The data presented demonstrate that, by the appropriate design of oligonucleotides and by performance of a nested PCR under appropriate conditions, it is possible to obtain sequence on a battery of species with a minimum of oligonucleotide primers. A total of 5.2 kb of cross-species sequence was generated with RAWTS. The results indicate that (1) 69% of the amino acids in the catalytic domain, but only 23% of the amino acids in the activation peptide, are identical in humans and the six species; (2) the catalytic domain evolves at a slower rate, but the extent and pattern of conservation of amino acids in the activation peptide suggest that the peptide functions as more than a cleavage spacer that separates the heavy and light chains in the catalytically inactive zymogen; (3) 37% of the amino acids in the activation peptide and 34% of the amino acids in the catalytic domain are factor IX-specific; i.e., they are either identical or changed in a highly conservative fashion in factor IX, but not in other related coagulation proteases; (4) these conserved factor IX-specific amino acids fall into three clusters, which are candidates for involvement in the protein interactions specific to factor IX; (5) there is a human-specific deletion after lysine 142 and a rodent-specific insertion after alanine 161; (6) in guinea pig, the insertion is associated with a seven-amino-acid repeat that corresponds to a perfect repeat of a 21-bp sequence; (7) humans have lost a potential N-glycosylation site that is conserved in the other species; (8) in each species, a few nonconservative changes occur in amino acids that are otherwise completely conserved, suggesting that compensatory mutations may have occurred; and (9) when compared to that of mouse, the amino acid identity with guinea pig factor IX is no greater than that found for the non-rodent species, a result compatible with the postulated increased rate of evolution in rodents.

Amino Acid Sequence↗

Nucleotide sequence of a cDNA coding for bovine mitochondrial aspartate aminotransferase.

Aspartate aminotransferase is a pyridoxal-phosphate dependent enzyme which plays a key role in cell metabolism. We describe the cloning and sequence analysis of the cDNA encoding bovine mitochondrial aspartate aminotransferase and compare the sequence with those of isoenzymes from other mammalian species. An adult bovine heart cDNA library constructed in lambda lambda gt11 was screened using two 32P-end labeled synthetic oligonucleotides. From the screening of the cDNA library two positive clones were isolated. A subclone in pEMBL18, 6B2, generated from the longest recombinant phage was further analyzed. This clone contains an insert of 2500 bp with an Open Reading Frame of 1287 bp that encodes a protein of 430 amino acids. The deduced amino acid sequence confirms previous results obtained by mass spectrometric sequencing. We calculated the percentage of amino acid identity for each protein pair and for each comparison the average number of amino acid substitution per site (Kaa); the lowest Kaa values were obtained from the comparison between the bovine and pig enzymes. This study shows that the rate of evolution of mammalian mitochondrial AspAT is lower and more constant than the equivalent cytosolic enzyme and adds to the growing body of knowledge on the evolution of the aspartate aminotransferase.

Amino Acid Sequence↗

[Post-traumatic necrotizing fasciitis].

We are reporting the case of a 39-year-old male, without notable previous history except for an important alcoholic and tobacco consumption, who suffered a bicycle accident resulting in a minor wound on the left elbow. The neglected wound evolved extremely rapidly towards a necrotizing fasciitis, which underwent further complications consisting of a heat shock and multivisceral failure that necessitated reanimation procedures. The patient benefited a triple antibiotic therapy (amoxicillin-clavulanic acid, ornidazole and levofloxacin) and an extensive surgical debridement. The progression was then slow but favourable. The patient is now in functional reeducation. This observation illustrates the rate of evolution of the lesions caused by necrotizing fasciitis and reminds on the importance of prompt therapy.

Adult↗

The pseudoautosomal regions, SHOX and disease.

The pseudoautosomal regions represent blocks of sequence identity between the mammalian sex chromosomes. In humans, they reside at the ends of the X and Y chromosomes and encompass roughly 2.7 Mb (PAR1) and 0.33 Mb (PAR2). As a major asset of recently available sequence data, our view of their structural characteristics could be refined considerably. While PAR2 resembles the overall sequence composition of the X chromosome and exhibits only slightly elevated recombination rates, PAR1 is characterized by a significantly higher GC content and a completely different repeat structure. In addition, it exhibits one of the highest recombination frequencies throughout the entire human genome and, probably as a consequence of its structural features, displays a significantly faster rate of evolution. It therefore represents an exceptional model to explore the correlation between meiotic recombination and evolutionary forces such as gene mutation and conversion. At least twenty-nine genes lie within the human pseudoautosomal regions, and these genes exhibit 'autosomal' rather than sex-specific inheritance. All genes within PAR1 escape X inactivation and are therefore candidates for the etiology of haploinsufficiency disorders including Turner syndrome (45,X). However, the only known disease gene within the pseudoautosomal regions is the SHORT STATURE HOMEBOX (SHOX) gene, functional loss of which is causally related to various short stature conditions and disturbed bone development. Recent analyses have furthermore revealed that the phosphorylation-sensitive function of SHOX is directly involved in chondrocyte differentiation and maturation.

Animals↗

Bovine seminal plasma proteins and their relatives: A new expanding superfamily in mammals.

BSP proteins represent three major proteins of bovine seminal plasma: BSP-A1/-A2, -A3 and -30 kDa. The BSP protein signature is characterized by two tandemly repeated fibronectin type 2 (Fn2) domains. Although classical affinity chromatography and protein sequencing have proven that the BSP protein homologs may be ubiquitous in mammals and functionally related to sperm capacitation, only the three bovine genes have been reported thus far. In this study, we report three new BSP protein-related genes from bovine, as well as other BSP protein-related DNA sequences from human, chimpanzee, mouse, rat, dog, horse and rabbit. Analysis of the relationships between all Fn2 domain-containing proteins revealed that the Fn2 domains found in BSP-related proteins have special features that distinguish them from non-BSP-related proteins. These features can be used to identify new BSP protein-related sequences. Further molecular evolutionary analysis of the BSP protein lineage revealed that all BSP proteins and their related sequences can be grouped into three subfamilies: BSPH4, BSPH5 and BSPH6, which indicates that the BSP protein family is much bigger than previously envisioned. More interestingly, the three BSP proteins in bovine within the BSPH4-subfamily were shown to evolve rapidly. The ratio of nonsynonymous to synonymous substitutions was higher than 1. The analysis also indicated that the rate of evolution was heterogeneous between the first and second Fn2 domains of the genes. These data may reflect that some amino acids in BSP proteins are under a strong positive selection after gene duplication and that each BSP protein evolves rapidly, possibly to acquire new functions.

Amino Acid Sequence↗

Snakes as agents of evolutionary change in primate brains.

Current hypotheses that use visually guided reaching and grasping to explain orbital convergence, visual specialization, and brain expansion in primates are open to question now that neurological evidence reveals no correlation between orbital convergence and the visual pathway in the brain that is associated with reaching and grasping. An alternative hypothesis proposed here posits that snakes were ultimately responsible for these defining primate characteristics. Snakes have a long, shared evolutionary existence with crown-group placental mammals and were likely to have been their first predators. Mammals are conservative in the structures of the brain that are involved in vigilance, fear, and learning and memory associated with fearful stimuli, e.g., predators. Some of these areas have expanded in primates and are more strongly connected to visual systems. However, primates vary in the extent of brain expansion. This variation is coincident with variation in evolutionary co-existence with the more recently evolved venomous snakes. Malagasy prosimians have never co-existed with venomous snakes, New World monkeys (platyrrhines) have had interrupted co-existence with venomous snakes, and Old World monkeys and apes (catarrhines) have had continuous co-existence with venomous snakes. The koniocellular visual pathway, arising from the retina and connecting to the lateral geniculate nucleus, the superior colliculus, and the pulvinar, has expanded along with the parvocellular pathway, a visual pathway that is involved with color and object recognition. I suggest that expansion of these pathways co-occurred, with the koniocellular pathway being crucially involved (among other tasks) in pre-attentional visual detection of fearful stimuli, including snakes, and the parvocellular pathway being involved (among other tasks) in protecting the brain from increasingly greater metabolic demands to evolve the neural capacity to detect such stimuli quickly. A diet that included fruits or nectar (though not to the exclusion of arthropods), which provided sugars as a neuroprotectant, may have been a required preadaptation for the expansion of such metabolically active brains. Taxonomic differences in evolutionary exposure to venomous snakes are associated with similar taxonomic differences in rates of evolution in cytochrome oxidase genes and in the metabolic activity of cytochrome oxidase proteins in at least some visual areas in the brains of primates. Raptors that specialize in eating snakes have larger eyes and greater binocularity than more generalized raptors, and provide non-mammalian models for snakes as a selective pressure on primate visual systems. These models, along with evidence from paleobiogeography, neuroscience, ecology, behavior, and immunology, suggest that the evolutionary arms race begun by constrictors early in mammalian evolution continued with venomous snakes. Whereas other mammals responded by evolving physiological resistance to snake venoms, anthropoids responded by enhancing their ability to detect snakes visually before the strike.

Animals↗

The effect of genetic drift on the variance/covariance components generated by multilocus additive x additive epistatic systems.

The effect of population bottlenecks on the components of the genetic variance/covariance generated by n neutral independent additive x additive loci has been studied theoretically. In its simplest version, this situation can be modelled by specifying the allele frequencies and homozygous effects at each locus, and an additional factor measuring the strength of the n-th order epistatic interaction. The variance/covariance components in an infinitely large panmictic population (ancestral components) were compared with their expected values at equilibrium over replicates randomly derived from the base population, after t bottlenecks of size N (derived components). Formulae were obtained giving the derived components (and the between-line variance) as functions of the ancestral ones (alternatively, in terms of allele frequencies and effects) and the corresponding inbreeding coefficient F(t). The n-th order derived component of the genetic variance/covariance is continuously eroded by inbreeding, but the remaining components may increase initially until a critical F(t) value is attained, which is inversely related to the order of the pertinent component, and subsequently decline to zero. These changes can be assigned to the between-line variances/covariances of gene substitution and epistatic effects induced by drift. Numerical examples indicate that: (1) the derived additive variance/covariance component will generally exceed its ancestral value unless epistasis is weak; (2) the derived epistatic variance/covariance components will generally exceed their ancestral values unless allele frequencies are extreme; (3) for systems showing equal ancestral additive and total non-additive variance/covariance components, those including a smaller number of epistatic loci may generate a larger excess in additive variance/covariance after bottlenecks than others involving a larger number of loci, provided that F(t) is low. Our results indicate that it is unlikely that the rate of evolution may be significantly accelerated after population bottlenecks, in spite of occasional increments of the derived additive variance over its ancestral value.

Animals↗

[Evolution of strategy and coverage rates for hepatitis B vaccination in France, a country with low endemicity].

Both HBV plasma derived vaccines and HBV recombinant vaccines have proved safe and highly immunogenic. In France, exhaustive population surveys have revealed a vaccine coverage rate of over 21.7% and very low three-dose vaccine coverage among infants (19.8%), children (23.3%), and adolescents. Among hospital staff, around 80 to 90% of physicians and health care personnel in public or private hospitals were vaccinated against hepatitis B and the level of coverage was higher among personnel accidentally exposed to blood (90 to 100%). Among risk groups, the specific prevention program against mother-infant transmission was unevenly applied, and between 25 to 45% of intravenous drug abusers, prisoners, or STD patients were vaccinated. These coverage rates are inadequate to obtain a significant reduction and control of hepatitis B infections in France. The complete eradication of HBV transmission might take another 20 years to achieve unless great efforts are made to vaccinate the general population (infants especially) and high-risk groups.

Adolescent↗

MR imaging evaluation of cancer extent: is there clinical relevance?

The traditional methods for selecting women for breast conservation therapy (BCT), coupled with adjuvant radiation therapy, have reduced recurrence rates of BCT to acceptable levels. These recurrence rates are still significant, however. They may be further affected by the application of more anatomically targeted radiation therapy. Preoperative MR imaging should theoretically reduce the local failure rate of BCT by at least 5%, with only a modest increase in the mastectomy rate. The evolution of BCT to include more targeted radiation therapy and ablation should place an even larger emphasis on accurate tumor localization and has the potential to allow BCT to become more prevalent and effective.

Breast Neoplasms↗

Kidney preservation with IGL-1 solution: a preliminary report.

The University of Wisconsin (UW) solution is the most commonly used preservation solution. However, a new preservation solution-IGL-1-contains an inversion of K and Na concentrations and substitution of polyethylene glycol for hydroxyethyl starch in the UW solution. The present study is the first clinical experience on the outcome of kidneys preserved in IGL-1 solution. From June 2003 to June 2004, 119 cadaveric kidneys were retrieved and stored in IGL-1 solutions; among the 119 organs, this study includes 37 IGL-1-preserved kidneys that were locally transplanted versus 33 kidneys stored in University of Wisconsin (UW) solution that were also locally transplanted. The groups were comparable with regard to donor and recipient characteristics. Renal function outcome was evaluated by comparing delayed graft function (DGF) rates, the evolution of serum creatinine, daily urine output, and creatinine clearance. Biopsies were performed after reperfusion to evaluate apoptosis. The incidence of DGF was 5.71% among IGL-1 kidneys and 13.79% among UW kidneys. Creatinine values were significantly lower among the IGL-1 group from 2 to 14 days postoperative and at 1 month. Daily urinary output did not show any significant differences between the two groups. IGL-1 kidneys had a superior creatinine clearance during the first 15 postoperative days compared to UW kidneys. Kidneys preserved in IGL-1 solution showed fewer apoptotic cells compared to kidneys preserved in UW solution. This preliminary report suggests a superiority of IGL-1 for the immediate outcome of transplanted kidneys.

Adenosine↗

Gene duplication and inactivation in the HPRT gene family.

Hypoxanthine phosphoribosyltransferase (HPRT1) is a key enzyme in the purine salvage pathway, and mutations in HPRT1 cause Lesch-Nyhan disease. The studies described here utilized targeted comparative mapping and sequencing, in conjunction with database searches, to assemble a collection of 53 HPRT1 homologs from 28 vertebrates. Phylogenetic analysis of these homologs revealed that the HPRT gene family expanded as the result of ancient vertebrate-specific duplications and is composed of three groups consisting of HPRT1, phosphoribosyl transferase domain containing protein 1 (PRTFDC1), and HPRT1L genes. All members of the vertebrate HPRT gene family share a common intron-exon structure; however, we have found that the three gene groups have distinct rates of evolution and potentially divergent functions. Finally, we report our finding that PRTFDC1 was recently inactivated in the mouse lineage and propose the loss of function of this gene as a candidate genetic basis for the phenotypic disparity between HPRT-deficient humans and mice.

Animals↗