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T Hubbard

Publications and source records attributed to T Hubbard.

33 records · Page 2Linked to original sources
PubMed1996

Update on protein structure prediction: results of the 1995 IRBM workshop.

Computational tools for protein structure prediction are of great interest to molecular, structural and theoretical biologists due to a rapidly increasing number of protein sequences with no known structure. In October 1995, a workshop was held at IRBM to predict as much as possible about a number of proteins of biological interest using ab initio prediction of fold recognition methods. 112 protein sequences were collected via an open invitation for target submissions. 17 were selected for prediction during the workshop and for 11 of these a prediction of some reliability could be made. We believe that this was a worthwhile experiment showing that the use of a range of independent prediction methods and thorough use of existing databases can lead to credible and useful ab initio structure predictions.

Animals↗
PubMed1995

Discovery of an orally bioavailable NK1 receptor antagonist, (2S,3S)-(2-methoxy-5-tetrazol-1-ylbenzyl)(2-phenylpiperidin-3-yl)amine (GR203040), with potent antiemetic activity.

The antiemetic, pharmacokinetic, and metabolic profile of CP-99,994, a potent NK1 receptor antagonist, has been carefully evaluated. As a result we began a medicinal chemistry program which initially identified a 3-furanyl analogue (6) with improved antiemetic potency and a methyl sulfone (5) with enhanced metabolic stability and oral bioavailability. The improved pharmacokinetic profile of methyl sulfone (5) was associated with its low lipophilicity, and a therefore a number of heterocyclic analogues with reduced log D were synthesized. Out of this program emerged 19 (GR203040), a tetrazolyl-substituted analogue. Tetrazole 19 inhibits radiation-induced emesis in the ferret with high potency when administered both subcutaneously and orally, has a long duration of action, and has high oral bioavailability in the dog. Tetrazole 19 is currently undergoing evaluation as a novel approach for the control of emesis associated with, for example, cancer chemotherapy.

Animals↗
PubMed1995

SCOP: a structural classification of proteins database for the investigation of sequences and structures.

To facilitate understanding of, and access to, the information available for protein structures, we have constructed the Structural Classification of Proteins (scop) database. This database provides a detailed and comprehensive description of the structural and evolutionary relationships of the proteins of known structure. It also provides for each entry links to co-ordinates, images of the structure, interactive viewers, sequence data and literature references. Two search facilities are available. The homology search permits users to enter a sequence and obtain a list of any structures to which it has significant levels of sequence similarity. The key word search finds, for a word entered by the user, matches from both the text of the scop database and the headers of Brookhaven Protein Databank structure files. The database is freely accessible on World Wide Web (WWW) with an entry point to URL http: parallel scop.mrc-lmb.cam.ac.uk magnitude of scop.

Amino Acid Sequence↗
PubMed1995

Modified crush-avulsion anastomosis model on the rat femoral vein.

A crush-avulsion anastomosis model was established on the rat femoral vein. Saline or heparin was used as a luminal topical agent and was allowed to contact the damaged endothelium for 10 min. Patency and coagulation parameters were investigated for 1 week. The heparin treated group had a patency rate of 93% at 1 hr vs. 13% for the saline treated group (P < 0.001). At 7 days, the heparin treated group had an 87% patency vs. 7% for the saline-treated group (P < 0.001). Scanning electron micrography (SEM) provided evidence of the deposition of the components of early thrombosis in the crushed venous wall. In contrast, the SEM of the heparin treated group shows a paucity of any evidence of thrombus. These results indicate that the rat vein crush-avulsion model is a reliable and reproducible thrombosis model with low patency. The methods used with the topical agent may improve the patency rate in crush avulsion injuries.

Anastomosis, Surgical↗
PubMed1992

Complex cranial base trauma resulting from recreational fireworks injury: case reports and review of the literature.

Two patients who sustained complex skull base trauma secondary to recreational fireworks injuries are reported. Initial assessment and management included axial and coronal computerized tomography, control of hemorrhage, debridement of wound and brain, isolation of brain from external environment, and reconstruction of the cranial base floor. Secondary orbital and facial reconstruction used available bone fragments and iliac bone graft in one patient and vascularized free tissue transfer in the other. In both patients, reconstruction of both the intracranial and extracranial compartments was successful with acceptable cosmetic result. Modification of multiple conventional approaches, along with a multispecialty surgical team, was used to deal effectively with these unique cases.

Adult↗
PubMed1991

Use of recombinant hirudin to increase the patency rate of microanastomosis in a rabbit model.

Microvascular surgical techniques now play an extremely important role in reconstructive surgery. Failures still persist and are most commonly due to thrombotic occlusion of the microvascular anastomosis. Five to 20% of all free tissue transfers and replants are affected. A logical step in the effort to resolve this problem would be the infusion of the newly available recombinant hirudin (r-hirudin). The value of r-hirudin in microvascular surgery has not been investigated. An animal model mimicking the thrombotic mechanisms similar to those in the clinical situation has been described in which a length of rabbit femoral artery is excised, turned inside out and reinserted into the vessel with two standard microvascular anastomoses. The major factors in clinical anastomosis failure are represented in this animal model by medial disruption, imperfect vessel wall alignment, needle holes, trauma, foreign suture material and changes in flow. The type III adventitial collagen turned inward reproduces the clinical problem of adventitial strands becoming caught in the anastomosis. A predictable rate of thrombosis results depending on inversion graft length: a 2 mm segment has an occlusion rate at one week of about 30%. Using this model heparin infusions significantly decrease thrombosis rates compared to saline. Using an almost identical model we have begun a study the effect of r-hirudin on microvascular patency. New Zealand White male rabbits were anaesthetized with ketamine and xylazine. Through a groin incision the femoral vein was catheterized and tubing connected to an infusion pump. The femoral artery was exposed, and the adventitia aggressively removed since it is difficult to minimally debride adventitia in a reproducible fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1989

Protein engineering and design.

Rapid advances in site-directed mutagenesis and total gene synthesis combined with new expression systems in prokaryotic and eukaryotic cells have provided the molecular biologist with tools for modification of existing proteins to improve catalytic activity, stability and selectivity, for construction of chimeric molecules and for synthesis of completely novel molecules that may be endowed with some useful activity. Such protein engineering can be seen as a cycle in which the structures of engineered molecules are studied by X-ray analysis and two-dimensional nuclear magnetic resonance. The results are used in the improvement of the design by using knowledge-based procedures that exploit facts, rules and observations about proteins of known three-dimensional structure.

Amino Acid Sequence↗
PubMed1988

18th Sir Hans Krebs lecture. Knowledge-based protein modelling and design.

A systematic technique for protein modelling that is applicable to the design of drugs, peptide vaccines and novel proteins is described. Our approach is knowledge-based, depending on the structures of homologous or analogous proteins and more generally on a relational data base of protein three-dimensional structures. The procedure simultaneously aligns the known tertiary structures, selects fragments from the structurally conserved regions on the basis of sequence homology, aligns these with the 'average structure' or 'framework', builds on the loops selected from homologous proteins or a wider database, substitutes sidechains and energy minimises the resultant model. Applications to modelling an homologous structure, tissue plasminogen activator on the basis of another serine proteinase, and to modelling an analogous protein, HIV viral proteinase on the basis of aspartic proteinases, are described. The converse problem of ab initio design is also addressed: this involves the selection of an amino acid sequence to give a particular tertiary structure, in this case a symmetrical domain of two Greek-key motifs.

Base Sequence↗
PubMed1981

Cellular immune response during uncomplicated genital infection with Chlamydia trachomatis in humans.

A lymphocyte transformation (LT) assay for the study of the cellular immune response to Chlamydia trachomatis in humans is described. Subjects studied included 9 newborns whose mothers were C. trachomatis culture negative, 16 seronegative, sexually inexperienced adults, and 107 patients seen at a sexually transmitted disease clinic, including 31 men presenting with acute nongonococcal urethritis and 76 women with known or suspected uncomplicated gonorrhea or with uncomplicated C. trachomatis genital infection. LT stimulation indices (SI) were less than 3.5 in newborns and normal adults, as well as 11 of 12 seronegative, isolation-negative sexually transmitted disease clinic subjects. LTSI greater than 3.5 was found only with subjects who were sero- or culture positive for C. trachomatis. Among men with nongonococcal urethritis, the LTSI correlated better with culture than with antibody. Among women, the LTSI correlated better with antibody than with culture. LTSI decline significantly 3 to 4 weeks after curative therapy in men with nongonococcal urethritis, suggesting that LT response is short-lived and that the LTSI may be an indicator of acute C. trachomatis infection. The sensitivity, specificity, and predictive value of a positive LT assay and of serum and local antibody tests, in terms of C. trachomatis infection defined as positive isolation, were also compared. The predictive value of a positive LTSI for C. trachomatis infection was generally low in the sexually transmitted disease clinic patients: 62% in men with nongonococcal urethritis and 37% in women. However, this study did show the LT assay to be a useful specific test for monitoring the cellular immune response to C. trachomatis infection.

Antibodies, Bacterial↗
PubMedDate not supplied

Out of the shadows.

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Burnout, Professional↗