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Biomedical subjects

D J Stevens

Publications and source records attributed to D J Stevens.

At least 19 recordsLinked to original sources
PubMed2006

Avian and human receptor binding by hemagglutinins of influenza A viruses.

An understanding of the structural determinants and molecular mechanisms involved in influenza A virus binding to human cell receptors is central to the identification of viruses that pose a pandemic threat. To date, only a limited number of viruses are known to have infected humans even sporadically, and this has recently included the virulent H5 and H7 avian viruses. We compare here the 3-dimensional structures of H5 and H7 hemagglutinins (HA) complexed with avian and human receptor analogues, to highlight regions within the receptor binding domains of these HAs that might prevent strong binding to the human receptor.

Carbohydrate Sequence↗
PubMed2005

A simple method for assessing muscle function in common marmosets.

A novel method of assessing muscle function in the common marmoset was developed as part of a multidisciplinary long-term study. The method involved home cage presentation of a weight-pulling task. Over a 4-5 month period, 38 of 42 animals were successfully trained to displace weights of up to 920 g (mean 612+/-20 g). Performance, following initial training, was stable and independent of gender or body weight.

Animals↗
PubMed2005

Studies into using manure in a biorefinery concept.

Animal manure is an underutilized biomass resource containing a large amount of organic carbon that is often wasted with the existing manure disposal practices. A research project funded by the US Department of Energy explored the feasibility of using manure via the sugar platform in a biorefinery, converting the carbon from fiber to biochemicals. The results showed that (1) fiber was the major component of manure dry material making up approx 50%, 40%, and 36% of the dry dairy, swine, and poultry manure material, respectively; within dairy manure, more than 56% of the dry matter was in particles larger than 1.680 mm; (2) in addition to being a carbon source, manure could provide a variety of nutrient for fungi T. reesei and A. phoenicis to produce cellulase; (3) the hemicellulose component in the manure fiber could be readily converted to sugar through acid hydrolysis; while concentrated acid decrystallization treatment was most effective in manure cellulose hydrolysis; (4) purification and separation was necessary for further chemical conversion of the manure hydrolysate to polyols through hydrogenation; and (5) the manure utilization strategy studied in this work is currently not profitable.

Agriculture↗
PubMed2004

H1 and H7 influenza haemagglutinin structures extend a structural classification of haemagglutinin subtypes.

Comparing the structures of H3, H5 and H9 subtype haemagglutinins, we deduced a structural basis for including all 15 influenza subtypes in four clades. H3, H5 and H9 represent three of these clades; we now report the structure of an H7 HA as a representative of the fourth clade. We confirm the structure of the turn at the N-terminus of the conserved central alpha-helix of HA2, and the combination of ionisable residues near the "fusion peptide" as clade-specific features. We compare the structures of three H1 HAs with H5 HA in the same clade, to refine our previous classification and we confirm the division of the clades into two groups of two. We also show the roles of carbohydrate side chains in the esterase-fusion domain boundaries in the formation of clade-specific structural markers.

Amino Acid Sequence↗
PubMed2004

The structure and receptor binding properties of the 1918 influenza hemagglutinin.

The 1918 influenza pandemic resulted in about 20 million deaths. This enormous impact, coupled with renewed interest in emerging infections, makes characterization of the virus involved a priority. Receptor binding, the initial event in virus infection, is a major determinant of virus transmissibility that, for influenza viruses, is mediated by the hemagglutinin (HA) membrane glycoprotein. We have determined the crystal structures of the HA from the 1918 virus and two closely related HAs in complex with receptor analogs. They explain how the 1918 HA, while retaining receptor binding site amino acids characteristic of an avian precursor HA, is able to bind human receptors and how, as a consequence, the virus was able to spread in the human population.

Amino Acid Sequence↗
PubMed2001

X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs.

The three-dimensional structures of avian H5 and swine H9 influenza hemagglutinins (HAs) from viruses closely related to those that caused outbreaks of human disease in Hong Kong in 1997 and 1999 were determined bound to avian and human cell receptor analogs. Emerging influenza pandemics have been accompanied by the evolution of receptor-binding specificity from the preference of avian viruses for sialic acid receptors in alpha2,3 linkage to the preference of human viruses for alpha2,6 linkages. The four new structures show that HA binding sites specific for human receptors appear to be wider than those preferring avian receptors and how avian and human receptors are distinguished by atomic contacts at the glycosidic linkage. alpha2,3-Linked sialosides bind the avian HA in a trans conformation to form an alpha2,3 linkage-specific motif, made by the glycosidic oxygen and 4-OH of the penultimate galactose, that is complementary to the hydrogen-bonding capacity of Gln-226, an avian-specific residue. alpha2,6-Linked sialosides bind in a cis conformation, exposing the glycosidic oxygen to solution and nonpolar atoms of the receptor to Leu-226, a human-specific residue. The new structures are compared with previously reported crystal structures of HA/sialoside complexes of the H3 subtype that caused the 1968 Hong Kong Influenza virus pandemic and analyzed in relation to HA sequences of all 15 subtypes and to receptor affinity data to make clearer how receptor-binding sites of HAs from avian viruses evolve as the virus adapts to humans.

Amino Acid Sequence↗
PubMed2000

Developmental trade-offs and life histories: strategic allocation of resources in caddis flies.

Resource allocation trade-offs during development are potentially very important in the evolution of organism morphology and life-history strategy However, they have rarely been demonstrated empirically. To what extent the division of limited resources between growing organs is a consequence of particular developmental pathways or varies strategically in line with life-history predictions is unknown. It has been demonstrated in a number of holometabolous insects that altering the resources available at pupation changes the pattern of allocation to adult tissues, but this has not been examined in a life-history context. Using caddis flies (Trichoptera), we show here that the effect of depleted larval resources on the pattern of somatic and reproductive investment is not fixed but varies between species with different life-history patterns. In particular, we demonstrate that, in a long-lived species, thorax size is preserved, which contrasts with the pattern previously observed in a short-lived species. That the adult body can be differentially altered by the same resource depletion in the larvae demonstrates that the allocation of resources amongst body parts is not a consequence of fixed pathways during development. Rather, the allocation of resources during development can occur in a manner consistent with the minimization of the effects on adult fitness.

Animals↗
PubMed1998

Structure of the hemagglutinin precursor cleavage site, a determinant of influenza pathogenicity and the origin of the labile conformation.

The membrane fusion potential of influenza HA, like many viral membrane-fusion glycoproteins, is generated by proteolytic cleavage of a biosynthetic precursor. The three-dimensional structure of ectodomain of the precursor HA0 has been determined and compared with that of cleaved HA. The cleavage site is a prominent surface loop adjacent to a novel cavity; cleavage results in structural rearrangements in which the nonpolar amino acids near the new amino terminus bury ionizable residues in the cavity that are implicated in the low-pH-induced conformational change. Amino acid insertions at the cleavage site in HAs of virulent avian viruses and those of viruses isolated from the recent severe outbreak of influenza in humans in Hong Kong would extend this surface loop, facilitating intracellular cleavage.

Bromelains↗
PubMed1995

Genomic structure and sequence of the Fugu rubripes glucose-6-phosphate dehydrogenase gene (G6PD).

To investigate the organization of the compact genome of the puffer fish Fugu rubripes at the level of an individual housekeeping gene, we have cloned and sequenced the glucose-6-phosphate dehydrogenase (G6PD) gene from this fish and compared it to the corresponding human gene. The intron/exon structure of the two genes is identical throughout the protein coding regions. The puffer fish gene is four times smaller than the human gene--the difference is accounted for by the fact that the puffer fish gene has smaller introns. Intron 2 is the largest intron in both species. We have constructed a molecular phylogeny for 10 G6PD protein sequences. The sequences fall in the expected arrangement based on established phylogenetic relationships, with the Plasmodium falciparum sequence the most widely diverged.

Amino Acid Sequence↗
PubMed1995

New glucose-6-phosphate dehydrogenase mutations associated with chronic anemia.

We have identified the glucose-6-phosphate dehydrogenase mutations responsible for enzyme deficiency in nine individuals with chronic nonspherocytic hemolytic anemia. We found the variants Tokyo, Iowa, Shinshu, and Guadalajara in British subjects and Kobe in an Italian. In addition we have determined the variant Corum has the mutation 820 G-->A and have found in British subjects the mis-sense mutations 224 T-->C, 488 G-->A and 833 C-->T which have not been described before. Some, but not all, of the mutations involve amino acids located near putative substrate binding sites.

Anemia, Hemolytic↗
PubMed1989

Acinous cell carcinoma of the larynx.

Acinous cell tumours of the larynx and trachea are extremely rare. A recent review of the literature has only found four reported cases. This short report describes such a patient and discusses her management in the light of previous articles. In view of its rarity in the laryngotracheal area and the uncertainty in the way in which the tumour should be managed, we thought the following case report and review of the literature would be of interest.

Carcinoma↗
PubMed1989

Carcinoma of the pharyngeal pouch.

The condition of carcinoma arising in a pharyngeal pouch is rare. It has been described in relation to long standing pouches and in pouches previously treated by the Dohlman's operation. Three additional cases of carcinoma of the pharyngeal pouch are described.

Aged↗
PubMed1988

Neurofibromas of the paranasal sinuses.

Two cases of neurofibroma of the paranasal sinuses are presented. The tumours presented as space-occupying lesions and were treated by local excision. Histologically one was a typical neurofibroma, whilst the other showed some features of a schwannoma. The patients show no evidence of tumour recurrence at 18 and 6 months respectively.

Adult↗
PubMed1988

Papillary endothelial hyperplasia in the nose.

Benign papillary endothelial hyperplasia is a very rare lesion of the nasal cavity; histologically, it may be mistaken for an angiosarcoma. An awareness of this and the ways in which it differs from angiosarcoma will prevent incorrect diagnosis and inappropriate treatment by surgery or radiotherapy. A case report of each condition involving the nasal cavity is presented.

Adult↗