Science funding. The National Advisory Environmental Health Sciences Council.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Henderson.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Rounded toothbrush bristle tips are desirable because they are less likely to abrade hard and soft tissue and restorative materials than sharp-pointed bristles. Studies evaluating different types of toothbrushes have compared the degree of the end-roundness of different brands of toothbrushes, but have yielded conflicting results. Nine studies and three methods of evaluating end-rounding are reviewed in this article. Within the limits of the review, it appears that visual inspection of a bristle tip by scanning electron microscopy or a stereomicroscope at a 45-degree angle is the technique of choice for evaluating end-roundness. Of the 9 studies reviewed, 3 studies that used the 45-degree microscopic techniques provide the most useful information of toothbrush bristle end-roundness to date. Of the brushes compared in these three studies, Crest Complete and Improved Crest Complete toothbrushes were shown to have the highest degree of end-roundness. Future research should include longitudinal studies to clarify the relationship of the degree of end-rounding of toothbrush bristles and soft-and hard-tissue abrasion.
Images and diffraction patterns of frozen-hydrated thin crystals of phi 29 connectors were recorded using low dose microscopy and diffraction. The resolution obtained in two cases was 7 and 4 A, thus showing the suitability of this specimen for high-resolution studies. Seven of the best images and three of the best electron diffraction patterns were analysed semiquantitatively. The best image showed the presence of two connectors per unit cell (165 A x 165 A), each having an internal 4-fold axis and being related to one-another by 2-fold and 2-fold screw axes in the space group p42(1)2. Internal phase comparison within the best image showed good phase residuals for p42(1)2 and all its sub-groups. The other images were consistent with this interpretation taking into consideration the possible crystal tilt and specimen drift. We conclude that the most likely crystal space group is p42(1)2. Electron diffraction patterns were consistent with this assignment, but none of the patterns showed the precise 422 symmetry expected, almost certainly because the crystals were slightly tilted (2 to 5 degrees).
Explore the source record for details and available documents.
OBJECTIVE: To assess retrospectively the outcome and morbidity of Iridium-192 brachytherapy in the treatment of oral cancers. DESIGN: Retrospective audit of cases treated between 1981 and 1991. SETTING: Newcastle upon Tyne, England. SUBJECTS: 73 patients with oral cancer treated with Iridium-192. MAIN OUTCOME MEASURES: Local control, crude and cause specific survival, and local morbidity. RESULTS: Seventy four cases of squamous cell carcinoma of the oral cavity were treated using interstitial Iridium-192. The disease specific 5-year survival rates were 69% for T1, 67% for T2, and 0% for T3 tumours. Mortality from recurrent cancer was 20%, and from intercurrent disease was 28%. The incidence of major radiation induced morbidity was 11%, and the local control rate was 81% for T1, 69% for T2, and 50% for T3 tumours. CONCLUSION: Interstitial radiotherapy remains a viable and valuable mode of treatment for a small proportion of patients presenting with early (T1 and T2) oral cancers.
Explore the source record for details and available documents.
The incidence of non-Hodgkin's lymphoma was analysed in over 70,000 kidney transplant recipients and over 10,000 heart, heart-lung or lung transplant recipients. An increased incidence of lymphomas during the first posttransplant year was observed in cadaver kidney recipients as compared to related kidney recipients, in thoracic organ recipients as compared to kidney recipients, in heart-lung recipients as compared to heart or lung recipients, in patients transplanted in North America as compared to patients transplanted in Europe, in patients receiving cyclosporine in combination with azathioprine as compared to patients with other immunosuppressive regimens, and in patients receiving ATG/ALG or monoclonal OKT3 for rejection prophylaxis.
Between 1984 and 1990, 257 cases of Haemophilus influenzae type b (Hib) meningitis occurred in children under five years of age in Western Australia. We obtained information on possible sequelae in 131 cases (all non-Aboriginal) by medical record review and parental interview, and in a further 116 cases (60 non-Aboriginal, 56 Aboriginal) by medical record review only; no follow-up information was available for ten children (nine non-Aboriginal, 1 Aboriginal). The incidence of Hib meningitis in children under five years of age was 26.3 per 100,000 for non-Aboriginal and 152.2 per 100,000 for Aboriginal children. The case fatality rate was 3.5% for non-Aboriginal children and 14.0% for Aboriginal children. Sequelae were recorded for 17.1% of non-Aboriginal and 22.4% of Aboriginal children who survived Hib meningitis. Surviving Aboriginal children experienced severe sequelae following Hib meningitis almost three times more frequently than surviving non-Aboriginal children (10.5% vs 3.6%), although mild and moderate sequelae were not more common in Aboriginal children. The information on incidence and severity of sequelae in this study was obtained by chart review and parental interview, and hence may be subject to error or bias, particularly for mild and moderate disabilities. Outcomes like death and severe sequelae, such as cerebral palsy and profound intellectual and physical disability, are less subject to bias. Of Aboriginal children who contracted Hib meningitis in Western Australia over the study period, 22.8% either died or had severe sequelae, while only 7.0% of non-Aboriginal children experienced these severe outcomes.
Two-dimensional crystals of halorhodopsin (HR), in space group p42(1)2 (a = 102 A) have been obtained using the overexpressing Halobacterium halobium strain D2. An HR membrane fraction with the same buoyant density as purple membrane (HR-PM) was obtained by homogenization and sucrose gradient purification and used for electron cryomicroscopic analysis. Electron micrographs and electron diffraction patterns of HR-PM were recorded at liquid nitrogen temperatures. The micrographs showed significant diffraction out to 9 A resolution optically and to 6 A after computer processing. By combining data from electron micrographs and electron diffraction patterns, a projection map of HR was calculated. The crystal form of the isolated HR consists of one membrane in which alternating halorhodopsin tetramers are oriented in opposite directions across the membrane. It is not known whether this occurs by misinsertion of some of the molecules in vivo, or by adventitious fusion at some point during isolation. The projected structure of the HR molecule to a resolution of 6A is almost identical to that found for bacteriorhodopsin (BR). This physical structural similarity thus complements the known sequence relatedness to BR.
With the goal of obtaining sufficient quantities of seven-helix G-protein-coupled receptors for structural analysis, we have studied the functional expression of a rat neurotensin receptor cDNA in Escherichia coli with and without a signal sequence and as a fusion with the gene coding for maltose-binding protein. The addition of an N-terminal signal peptide resulted in increased expression levels. In vitro translation at a high level revealed that the codon usage of the rat neurotensin receptor cDNA was not critical for overproduction. Expression of neurotensin receptor cDNA fused to the 3' end of the gene encoding maltose-binding protein resulted in a 40-fold increase in neurotensin-binding sites. Binding of [3H]neurotensin to intact bacteria or E. coli membranes was saturable, with a dissociation constant, KD, of 0.23 nM (Bmax. = 450 sites/bacterium or 15 pmol/mg of crude membrane protein). The binding properties of all recombinant receptors presented in this study were similar and corresponded to those of the high-affinity binding sites in rat brain. For immunological detection and future purification of neurotensin receptor, a C-terminal pentahistidine/c-myc tail was introduced. Western-blot analysis revealed the association of neurotensin receptor with E. coli membranes.
Light absorption by the visual pigment rhodopsin triggers, through G-protein coupling, a cascade of events in the outer segment of the rod cell of the vertebrate retina that results in membrane hyperpolarization and nerve excitation. Rhodopsin, which contains 348 amino acids, has seven helices that cross the disk membrane and its amino terminus is extracellular. A wealth of biochemical data is available for rhodopsin: 11-cis retinal is bound to lysine 296 in helix VII; glutamic acid 113 on helix III is the counterion to the protonated Schiff's base; a disulphide bridge, cystine 110-187, connects helix III to the second extracellular loop e2 (refs 13, 14); the carboxy terminus has two palmitoylated cysteines forming a cytoplasmic loop i4 (ref. 15); three intracellular loops i2, i3 and i4 mediate activation of the heterotrimeric G protein transducin; glutamic acid 135 and arginine 136 at the cytoplasmic end of helix III affect binding of transducin. But to provide a framework to interpret these data, not only for rhodopsin but for other G-protein-coupled receptors, requires the structure to be determined. Here we present a projection map of rhodopsin showing the configuration of the helices.
Explore the source record for details and available documents.
Structural changes are central to the mechanism of light-driven proton transport by bacteriorhodopsin, a seven-helix membrane protein. The main intermediate formed upon light absorption is M, which occurs between the proton release and uptake steps of the photocycle. To investigate the structure of the M intermediate, we have carried out electron diffraction studies with two-dimensional crystals of wild-type bacteriorhodopsin and the Asp96-->Gly mutant. The M intermediate was trapped by rapidly freezing the crystals in liquid ethane following illumination with a xenon flash lamp at 5 and 25 degrees C. Here, we present 3.5 A resolution Fourier projection maps of the differences between the M intermediate and the ground state of bacteriorhodopsin. The most prominent structural changes are observed in the vicinity of helices F and G and are localized to the cytoplasmic half of the membrane.
The ring-like complement 'lesions' found on membranes of complement lysed cells comprise a complex of components C5b through C9 that coalesce to form hollow cylinders which penetrate the membrane bilayer and create lytic pores. Walls of these C5b-9 membrane attack complex cylinders may consist primarily of the C9 component, since samples of purified, isolated C9 can polymerize into cylindrical structures which appear identical with the fully assembled C5b-9 complex. The structure of these poly-C9 molecules has been investigated using the techniques of cryo-electron microscopy and single particle analysis. Sets of single poly-C9 particles viewed as rings were selected from cryo-EM images, then particles were aligned and treated by correspondence analysis to identify the principle interparticle similarities and variations. The highest ranking variation found was the presence or absence of a dense inner ring of protein density. Other important variations were interpreted as different types of particle tilt. These results were used in selecting a subgroup of untilted particles for averaging and symmetry analysis. The rotational power spectrum of the initial average suggested 13-fold symmetry. The 13-fold symmetry was used to select and group particles for further analysis. Individual particles were 13-fold rotational averaged and those with enhanced peripheral features were placed into either a right-handed subgroup or into a left-handed subgroup based on orientation of the peripheral features. Particles within each group were aligned and averaged, and a poly-C9 structure was produced which shows important structural details and from which the C9 monomer structure can be deduced. The poly-C9 structure contains a dense inner ring of diameter between 113-181 A and which is modulated into 13 discrete peaks with peak-to-peak separation of approx. 35 A. The dense inner ring is surrounded by a less dense, concentric outer rim extending to 254 A diameter. The outer rim contains projections that are contiguous with the inner peaks but are skewed relative to the ring radius to produce the appearance of a pin-wheel. These projections correspond with the peripheral features picked up in the rotationally averaged individual particles; the left- or right-handed orientation of projections may result from the up/down orientation of individual particles in ice. The C9 monomer structure within the cylinder is suggested by the density distribution. The monomer would be a rod with diameter of 35 A, oriented parallel to the cylinder axis and would be roughly perpendicular to a membrane.(ABSTRACT TRUNCATED AT 400 WORDS)
Patch averaging, a method of data analysis combining correlation averaging with multivariate statistical analysis, was applied to a high-resolution image of a purple membrane thin crystal. The observed variational patterns fall in two categories: non-crystallographic, related to small electron-optical distortions of the microscope, and crystallographic, conceivably related to variations in the locations of flexible segments of the polypeptide chain on the surface of the membrane.
Immunohistochemical staining of fresh frozen tissue to identify estrogen and progesterone receptors was tested as a means to supplant the dextran-coated charcoal assay in a small community hospital. Forty-three tumors were compared, yielding an overall concordance of 88% between immunohistochemical staining and the dextran-coated charcoal assay for determination of combined estrogen/progesterone receptor status. In addition, there was greater than 70% concordance for semiquantitative grades. Staining also revealed many other advantages, such as a 65% reduction in costs. For these reasons, the authors have abandoned the dextran-coated charcoal assay in favor of staining for estrogen/progesterone receptor status.