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Biomedical subjects

D T Jones

Publications and source records attributed to D T Jones.

At least 55 records · Page 3Linked to original sources
PubMed1999

Status report of the NAC particle therapy programme.

The 200 MeV cyclotron facility at the National Accelerator Centre has been operational since 1987. Between September 1988 and December 1997 a total of 973 patients (26,916 fields) had been treated on the 66 MeV p+Be isocentric neutron therapy system. Patients are currently being treated according to several protocols, including tumors of the head and neck, salivary gland and breast and soft tissue sarcomas, uterine sarcomas and paranasal sinuses. A multiblade post-collimator trimmer has recently being installed. This device provides improved neutron beam shaping capability. Between September 1993 and December 1997 a total of 243 patients (4008 fields) had been treated (mainly intracranial stereotactic irradiations) on the fixed horizontal 200 MeV proton therapy facility. The facility incorporates an innovative automatic patient positioning system. Two new fixed beam lines for proton therapy are presently being designed (horizontal and 30 degrees to the vertical) for an existing unused treatment vault. Spot scanning systems will be developed for both beam lines.

Head and Neck Neoplasms↗
PubMed1999

A challenge for high-precision radiation therapy: the case for hadrons.

Developments in Hadron therapy, i.e., fast neutrons, protons, pions, heavy ions and boron neutron capture therapy are reviewed. For each type of particle, operational and closed facilities are listed as well as planned new facilities. Improvements in clinical results have always been linked to technological developments and better physical selectivity of the irradiation. Exploring the benefit of further improvement in dose localization expected from protons and conformal therapy is the challenge for the coming years. The radiobiological rationale for high-LET radiation in cancer treatment, proposed in the fifties, is still valid and has not been contradicted by recent radiobiological findings. This justifies the planning of a therapy facility where protons and heavy ions (carbon ions) could be applied, under optimal physical and technical conditions. Appropriate selection between low- and high-LET radiation for a particular tumor is indeed a radiobiological problem, independent of technical development.

Boron Neutron Capture Therapy↗
PubMed1999

Beta propellers: structural rigidity and functional diversity.

Recently solved structures and proposed models have helped to reveal the structural characteristics of the beta-propeller fold, as well as the features that contribute to its high rigidity and stability. Possible strategies for identifying beta-propeller proteins in newly characterised sequences are helping to overcome the problems of predicting the beta-propeller fold from amino acid sequences.

Amino Acid Sequence↗
PubMed1999

Monte Carlo calculations to characterize the source for neutron therapy facilities.

Modern radiation treatment planning for photons includes full 3D modeling of the adsorbed dose distribution, accurate inclusion of the patient anatomy, and consideration of significant changes in material density and composition. Such efforts are founded in an accurate description of the radiation source and the beam delivery system. Modern fast neutron therapy facilities employ highly penetrating beams and isocentric beam delivery. Treatment planning is largely based on analytic models adapted from photon codes and interaction cross sections normalized to macroscopic attenuation. However, the recent PEREGRINE initiative at Lawrence Livermore Laboratory offers the possibility of fully stochastic modeling if the neutron source can be adequately described. In this article we report neutron source modeling of three high energy facilities. Neutron production is based on the intra-nuclear cascade model of the LAHET code while neutron transport through the beam delivery system is managed by MCNP using cross section libraries extended to 100 MeV neutron energy. PEREGRINE is then used to transport the neutron beam through typical phantoms. The resulting neutron sources are in excellent agreement with the limited experimental information and the measured phantom data are well described by the PEREGRINE transport using the LAHET/MCNP determined neutron sources.

Dose-Response Relationship, Radiation↗
PubMed1999

A consistent set of neutron kerma coefficients from thermal to 150 MeV for biologically important materials.

Neutron cross sections for nonelastic and elastic reactions on a range of elements have been evaluated for incident energies up to 150 MeV. These cross sections agree well with experimental cross section data for charged-particle production as well as neutron and photon production. Therefore they can be used to determine kerma coefficients for calculations of energy deposition by neutrons in matter. Methods used to evaluate the neutron cross sections above 20 MeV, using nuclear model calculations and experimental data, are described. Below 20 MeV, the evaluated cross sections from the ENDF/B-VI library are adopted. Comparisons are shown between the evaluated charged-particle production cross sections and measured data. Kerma coefficients are derived from the neutron cross sections, for major isotopes of H, C, N, O, Al, Si, P, Ca, Fe, Cu, W, Pb, and for ICRU-muscle, A-150 tissue-equivalent plastic, and other compounds important for treatment planning and dosimetry. Numerous comparisons are made between our kerma coefficients and experimental kerma coefficient data, to validate our results, and agreement is found to be good. An important quantity in neutron dosimetry is the kerma coefficient ratio of ICRU-muscle to A-150 plastic. When this ratio is calculated from our kerma coefficient data, and averaged over the neutron energy spectra for higher-energy clinical therapy beams [three p (68) + Be beams, and a d (48.5) + Be beam], a value of 0.94 +/- 0.03 is obtained. Kerma ratios for water to A-150 plastic, and carbon to oxygen, are also compared with measurements where available.

Biophysical Phenomena↗
PubMed1999

Risk of early closed reduction in cervical spine subluxation injuries.

OBJECT: The authors retrospectively reviewed 121 patients with traumatic cervical spine injuries to determine the risk of neurological deterioration following early closed reduction. METHODS: After excluding minor fractures and injuries without subluxation, the medical records and imaging studies (computerized tomography and magnetic resonance [MR] images) of 82 patients with bilateral and unilateral locked facet dislocations, burst fractures, extension injuries, or miscellaneous cervical fractures with subluxation were reviewed. Disc injury was defined on MR imaging as the presence of herniation or disruption: a herniation was described as deforming the thecal sac or nerve roots, and a disruption was defined as a disc with high T2-weighted signal characteristics in a widened disc space. Fifty-eight percent of patients presented with complete or incomplete spinal cord injuries. Thirteen percent of patients presented with a cervical radiculopathy, 22% were intact, and 9% had only transient neurological deficits in the field. Early, rapid closed reduction, using serial plain radiographs or fluoroscopy and Gardner-Wells craniocervical traction, was achieved in 97.6% of patients. In two patients (2.4%) closed reduction failed and they underwent emergency open surgical reduction. The average time to achieve closed reduction was 2.1+/-0.24 hours (standard error of the mean). The incidence of disc herniation and disruption in the 80 patients who underwent postreduction MR imaging was 22% and 24%, respectively. However, the presence of disc herniation or disruption did not affect the degree of neurological recovery, as measured by American Spinal Injury Association motor score and the Frankel scale following early closed reduction. Only one (1.3%) of 80 patients deteriorated, but that occurred more than 6 hours following closed reduction. CONCLUSIONS: Although disc herniation and disruption can occur following all types of traumatic cervical fracture subluxations, the incidence of neurological deterioration following closed reduction in these patients is rare. The authors recommend early closed reduction in patients presenting with significant motor deficits without prior MR imaging.

Cervical Vertebrae↗
PubMed1999

A novel governance system for enterprise information services.

The authors created a novel system for governing the enterprise information services (IS) of a large health care system. The governance organization is comprised of key members of the attending medical staff, hospital and health system administration, and the IS department. A method for defining the requirements and business case for proposed new systems was developed for use by departments requesting new or expanded information services. A Technology Architecture Guideline document was developed and approved to provide a framework for supported hardware and software technologies. IS policies are approved by the main governance council. All project proposals are reviewed by specialized governance committees and, if approved, are launched for further development. Fully developed proposals are reviewed, approved and prioritized for funding by the governance council. This novel organization provides the methodology and structure for enlightened peer review and funding for well developed IS project proposals.

Academic Medical Centers↗
PubMed1998

Classifying a protein in the CATH database of domain structures.

The CATH database of protein domain structures classifies structures according to their (C)lass, (A)rchitecture, (T)opology or fold and (H)omologous family (http://www.biochem.ucl.ac.uk/bsm/cath). Although the protocol used is mostly automatic, manual inspection is used to check assignments at some critical stages, such as the detection of very distantly related homologues and anologues and the assignment of novel architectures. Described in this article is a recently established facility to search the database with the coordinates of a newly determined structure. The CATH server first locates domain boundaries and then uses automatic sequence and structure comparison methods to assign this new structure to one or more of the domain families within CATH. Diagnostic reports are generated, together with multiple structural alignments for close relatives. The Server can be accessed over the World Wide Web (WWW) and mirror sites are planned to improve access.

Amino Acid Sequence↗
PubMed1998

Otologic management in children with the CHARGE association.

OBJECTIVES: To characterize otologic management of two patient groups, those with the CHARGE association and those not strictly labeled as CHARGE but with several features of the disorder (CHARGE-like), in order to determine: (1) the clinical validity and utility of managing CHARGE-like children in a similar manner to patients with the strictly defined CHARGE association, (2) the progression and prognosis of hearing loss and (3) the identification of factors that may predict the degree of hearing loss. DESIGN: Case series. SETTING: Tertiary care urban children's hospital. PATIENTS: 37 children, 22 in the CHARGE group and 15 in the CHARGE-like group. INTERVENTIONS: Otorhinolaryngologic and audiologic management. MAIN OUTCOME MEASURES: Otorhinolaryngologic and audiologic evaluation. RESULTS: All patients required otologic and/or audiologic care. Bilateral hearing loss was found in 32 patients (86%) and unilateral hearing loss in five patients (14%) when hearing was assessed in the absence of otitis media. Among the 32 patients with bilateral hearing loss, 31 (97%) were able to be fit with useful hearing aids. External ear anomalies were present in 25/37 (68%) patients, and middle ear and ossicular anomalies were identified in four cases (4/37, 11%), 36/37 (97%) patients required surgical management of otitis media. Three patients (3/37, 8%) exhibited radiographic evidence of inner ear deformity. Facial nerve dysfunction was noted in the records of 14/37 (38%) patients. No statistically significant difference was found when CHARGE and CHARGE-like patients were compared for degree of hearing loss (P = 0.5964), type of hearing loss (P = 0.2657), worsening of hearing level (P = 0.7908), or anomalies of the external ear (P = 0.6921), ossicles (P = 0.7908), inner ear (P = 0.7908) or facial nerve (P = 0.6409). Patients with external ear anomalies did not exhibit statistically different degrees (P = 0.3125) or types (P = 0.1515) of hearing loss from patients without auricular anomalies. The presence of facial nerve anomaly correlated significantly (P = 0.0021) with profound hearing loss. CONCLUSIONS: Children who are CHARGE-like may be may be considered equivalent in terms of otologic and audiologic management to children strictly defined as CHARGE patients. These children all require otologic care due to the high prevalence of middle ear disease and the underlying permanent hearing loss that is both stable and aidable. The degree of hearing loss cannot be predicted by external ear morphology, but may be predicted by facial nerve palsy.

Abnormalities, Multiple↗
PubMed1998

Do transmembrane protein superfolds exist?

A reliable and widely used transmembrane protein structure prediction algorithm was applied to five representative genomic sequence data sets in order to re-examine the hypothesis that in contrast to globular proteins there are no favored transmembrane protein fold families. When the number of predicted membrane spanning segments and the topology of these segments is taken into account then definite biases are observed which suggest that certain transmembrane topologies are significantly more common than others.

Algorithms↗
PubMed1998

Contemporary approaches to protein structure classification.

In a similar manner to sequence database searching, it is also possible to compare three-dimensional protein structure. Such methods can be extremely useful because a structural similarity may represent a distant evolutionary relationship that is undetectable by sequence analysis. In this review, we summarise the most popular structure comparison methods, show how they can be used for database searching, and then describe some of the most advanced attempts to develop comprehensive protein structure classifications. With such data, it is possible to identify distant evolutionary relationships, provide libraries of unique folds for structure prediction, estimate the total number of folds that exist, and investigate the preference for certain types of structures over others.

Databases, Factual↗
PubMed1998

Alterations of ocular surface gene expression in Sjögren's syndrome.

We have demonstrated that conjunctival epithelium of SS patients displays increased numbers of S-phase cells compared with non-dry eye controls. Moreover, in SS patients, these S-phase cells are distributed throughout all strata of the epithelium. The expression of MUC-1, a cell surface marker indicative of terminally differentiated epithelium, is localized to the conjunctival epithelial surface in SS and control patients. However, MUC-1 surface immunoreactivity appears to be reduced in SS epithelium, suggesting disruption of normal epithelial differentiation. A MUC-1 epitope exposed by pretreatment with neuraminidase is expressed in the basal and suprabasal layers of both patient populations. This antigen likely represents nascent, partially processed MUC-1(6) and may serve as a marker of the preterminally differentiated epithelial phenotype. Messenger RNA encoding several different inflammatory cytokines, including TNF-alpha, IL-1 alpha and beta, IL-6, IL-8, IL-10, and TGF-beta 1, is expressed at elevated levels within the conjunctival epithelium of SS patients compared with non-dry eye controls. Based on these observations, we have formulated a model to explain the ocular surface pathology of Sjögren's syndrome. We hypothesize that mechanical abrasion secondary to aqueous tear deficiency creates an inflammatory environment where conjunctival epithelial cells and lymphocytes are stimulated to produce and secrete various cytokines (i.e., IL-1, TNF-alpha, IL-6, IL-8, etc.) into the tear film. Elevated cytokine levels within the tear film, perhaps combined with reduced concentrations of essential lacrimal gland-derived factors (i.e., EGF, retinol), create an environment in which terminal differentiation of the ocular surface epithelium is impaired. As a consequence, the epithelium becomes hyperplastic, displaying increased mitotic activity, and loses the ability to express mature protective surface molecules including the membrane-bound mucin, MUC-1. This would imply that anti-inflammatory medications (i.e., corticosteroids or cyclosporine) that suppress the inflammatory component of this cascade may ameliorate the ocular surface disease and discomfort experienced by SS patients.

Cell Cycle↗
PubMed1998

Reduced survival and body size in the terrestrial isopod Porcellio scaber from a metal-polluted environment.

Terrestrial isopods (woodlice) may show trade-offs in life history parameters when exposed to toxins. We have shown previously [Jones and Hopkin (1996) Functional Ecology 10, 741-750] that woodlice which survive to reproduce in sites heavily polluted with metals from an industrial smelting works do not alter their reproductive allocation. This study investigates whether there are differences in the survival and body size of Porcellio scaber from these same populations. Specimens were collected from eight sites at different distances from the Avonmouth smelter, UK. The sites represented a gradient of concentrations of Zn, Cd, Pb and Cu in the woodlice, from background levels to a grossly contaminated sites close to the smelter. In laboratory trials, the number of days survived by starved males showed a significant decline with increased concentrations of Zn in those animals. The maximum size of both sexes declined significantly from the least to the most polluted sites. The most polluted sites had significantly fewer large animals. The cost of detoxifying assimilated metals appears to be reduced energy reserves and smaller body size.

Journal Article↗
PubMed1998

Assessing the impact of secondary structure and solvent accessibility on protein evolution.

Empirically derived models of amino acid replacement are employed to study the association between various physical features of proteins and evolution. The strengths of these associations are statistically evaluated by applying the models of protein evolution to 11 diverse sets of protein sequences. Parametric bootstrap tests indicate that the solvent accessibility status of a site has a particularly strong association with the process of amino acid replacement that it experiences. Significant association between secondary structure environment and the amino acid replacement process is also observed. Careful description of the length distribution of secondary structure elements and of the organization of secondary structure and solvent accessibility along a protein did not always significantly improve the fit of the evolutionary models to the data sets that were analyzed. As indicated by the strength of the association of both solvent accessibility and secondary structure with amino acid replacement, the process of protein evolution-both above and below the species level-will not be well understood until the physical constraints that affect protein evolution are identified and characterized.

Databases, Factual↗
PubMed1997

CATH--a hierarchic classification of protein domain structures.

BACKGROUND: Protein evolution gives rise to families of structurally related proteins, within which sequence identities can be extremely low. As a result, structure-based classifications can be effective at identifying unanticipated relationships in known structures and in optimal cases function can also be assigned. The ever increasing number of known protein structures is too large to classify all proteins manually, therefore, automatic methods are needed for fast evaluation of protein structures. RESULTS: We present a semi-automatic procedure for deriving a novel hierarchical classification of protein domain structures (CATH). The four main levels of our classification are protein class (C), architecture (A), topology (T) and homologous superfamily (H). Class is the simplest level, and it essentially describes the secondary structure composition of each domain. In contrast, architecture summarises the shape revealed by the orientations of the secondary structure units, such as barrels and sandwiches. At the topology level, sequential connectivity is considered, such that members of the same architecture might have quite different topologies. When structures belonging to the same T-level have suitably high similarities combined with similar functions, the proteins are assumed to be evolutionarily related and put into the same homologous superfamily. CONCLUSIONS: Analysis of the structural families generated by CATH reveals the prominent features of protein structure space. We find that nearly a third of the homologous superfamilies (H-levels) belong to ten major T-levels, which we call superfolds, and furthermore that nearly two-thirds of these H-levels cluster into nine simple architectures. A database of well-characterised protein structure families, such as CATH, will facilitate the assignment of structure-function/evolution relationships to both known and newly determined protein structures.

Databases, Factual↗
PubMed1997

Successful ab initio prediction of the tertiary structure of NK-lysin using multiple sequences and recognized supersecondary structural motifs.

A simple approach to protein tertiary structure prediction is described, based on the assembly of recognized supersecondary structural fragments taken from highly resolved protein structures by using a simulated annealing algorithm. The results of blind-testing this method on CASP2 target T0042 (pig NK-lysin) are presented. The predicted structure had a C alpha root-mean-square deviation of only 6.2 A from the experimental structure (and less than 5.0 A over the first 66 residues), and clearly had the correct fold when judged by using a number of objective measures. Despite the significant degree of success in this case, there is clearly much more development required before predictions with the accuracy of a good homology model can be made with this kind of approach.

Anti-Infective Agents↗
PubMed1997

Closure of a bronchopleural fistula using decalcified human spongiosa and a fibrin sealant.

Bronchopleural fistulas associated with empyema can occur as a life-threatening sequelae after pulmonary resection, most frequently occurring after pneumonectomy. With the use of the flexible bronchoscope, the bronchopleural fistula of a 62-year-old critically ill woman was permanently sealed with a fibrin sealant and a small section of demineralized human spongiosa. Closure of bronchopleural fistulas with the application of fibrin sealant plus human spongiosa may offer a valuable addition to the armament of therapeutic alternatives.

Adenocarcinoma↗