Biomedical subjects

R K Bryan

Publications and source records attributed to R K Bryan.

7 recordsLinked to original sources

PubMed1988

Estimation of missing cone data in three-dimensional electron microscopy.

The range of tilt angles for which projected images of two-dimensionally periodic specimens can be obtained in electron microscopy is limited both by technical aspects, such as goniometer design, and by the more fundamental limitation of object thickness. The lack of a full set of projections causes a missing cone in the reciprocal space data for the object, which will give an anisotropic resolution in a three-dimensional reconstruction and may cause the quality to be impaired by spurious features. The problem is governed by a linear operator which maps the three-dimensional object onto the set of projections. The eigenvalue spectrum of this operator is determined by the range of tilt angles and the spatial extent of the object. If the object is spatially restricted, the eigenvalues are all positive, and it is in principle possible to retrieve experimentally unavailable structure data from those that are measured. However, with restricted angle data, some of the eigenvalues are extremely small, so the problem is 'ill-conditioned' or sensitive to small perturbations in the data, such as noise, and it is necessary to regularize the solution. We applied two methods of band-limited extrapolation and inference on electron microscope data. Alternating projections onto convex sets regularized by a regularization parameter and a least squares estimation regularized by the Shannon entropy functional yield similar results if a close object extent constraint is available. The criterion of maximum entropy, however, allows a relaxation of this constraint.

Bacteria↗

PubMed1987

Pf1 Inovirus. Electron density distribution calculated by a maximum entropy algorithm from native fibre diffraction data to 3 A resolution and single isomorphous replacement data to 5 A resolution.

We have calculated the electron density distribution of the Pf1 strain of filamentous bacteriophage by a maximum entropy method. In the calculation we included native X-ray fibre diffraction data extending to 3 A resolution in the meridional direction on 60 layerlines that are resolved to 4 A in the equatorial direction, and lower resolution data from a single isomorphous derivative iodinated on the Tyr25 residue. The electron density map indicates that the 46-residue protein subunit is a single, gently curved stretch of alpha-helix with its axis at an angle of about 20 degrees to the axis of the virion. The alpha-helix subunit curves around the virion axis by about 1/6 turn, and decreases from about 27 A radius to about 13 A radius in the virion as the amino acid sequence of the subunit runs from the N terminus to the C terminus. Nearest-neighbour alpha-helical subunits are about 10 A apart along their length, and the axis of each subunit makes an unexpected negative angle with its nearest neighbours in the virion. To confirm the validity of the maximum entropy calculation, we have varied the constraints on the calculation. All variations result in either a map that is close to the original map or a map that cannot be interpreted in terms of secondary structure: we find only one map that makes structural sense.

Algorithms↗

PubMed1985

Long-term low-dose glucocorticoid therapy associated with remission of overt renal tubular acidosis in Sjögren's syndrome.

Renal tubular acidosis and focal interstitial inflammatory cell infiltrate secondary to Sjögren's syndrome remitted with low-dose glucocorticoid therapy over five and one half years in a patient with associated mild systemic lupus erythematosus. Such response has not been previously documented. This observation may have therapeutic applications for renal tubular acidosis associated with Sjögren's syndrome that deserve further investigation.

Acidosis, Renal Tubular↗

PubMed1985

Hypomorphic variant of the slow allele of C3 associated with hypocomplementemia and hematuria.

This report describes the first instance of a hypomorphic variant (C3*s) of the most common C3 allele, C3 Slow, which was detected in a four-year-old Caucasian boy with hematuria. Analysis of C3 phenotypes, as determined by agarose electrophoresis, showed a hypomorphic C3 Slow in the patient and a maternal aunt. Serum C3 concentration was significantly reduced in the patient and his mother (610 and 750 micrograms/ml; normal +/- 1 SD = 1,240 +/- 240 micrograms/ml) and was at the lower limits of normal in the affected aunt (770 micrograms/ml). The mother's phenotype was C3 S (? Ss) and she was the presumed carrier, since the father (C3 FS) had neither an abnormal C3 S band nor a low C3 concentration (980 micrograms/ml). Total hemolytic complement was significantly reduced only in the patient (19 units/ml; normal = 38 +/- 16). Hypomorphic C3 variants should be considered in the evaluation of decreased serum C3 levels.

Alleles↗

PubMed1984

Methods for specimen thickness determination in electron microscopy.

A new method is described for specimen thickness determination in transmission electron microscopy. This is carried out by marking specimens with gold particles and analysing the images of a tilt series by computer. The method makes it possible to distinguish populations of particles on different planes and calculate the distance between the planes with statistical variation. We have applied it to carbon films as test objects and compared the results with those obtained by transverse sectioning, STEM mass measurement, optical density and frequency change of a quartz crystal oscillator. We have then used the method for thickness measurement of multilayered protein crystals and thin sectioned cells.

Animals↗

PubMed1983

Maximum-entropy calculation of the electron density at 4 A resolution of Pf1 filamentous bacteriophage.

A 4 A electron-density map of Pf1 filamentous bacterial virus has been calculated from x-ray fiber diffraction data by using the maximum-entropy method. This method produces a map that is free of features due to noise in the data and enables incomplete isomorphous-derivative phase information to be supplemented by information about the nature of the solution. The map shows gently curved (banana-shaped) rods of density about 70 A long, oriented roughly parallel to the virion axis but slewing by about 1/6th turn while running from a radius of 28 A to one of 13 A. Within these rods, there is a helical periodicity with a pitch of 5 to 6 A. We interpret these rods to be the helical subunits of the virion. The position of strongly diffracted intensity on the x-ray fiber pattern shows that the basic helix of the virion is right handed and that neighboring nearly parallel protein helices cross one another in an unusual negative sense.

Bacteriophages↗

PubMed1977

Effect of minoxidil on blood pressure and hemodynamics in severe hypertension.

Eighteen patients with diastolic hypertension (100 to 120 mm Hg), in addition to propranolol, 160 mg daily, and hydrochlorothiazide, 100 mg daily, received progressively increased doses of either minoxidil or placebo in a double-blind crossover study. With minoxidil (average dose 19.7 mg) blood pressure decreased from 165/109 to 138/89 mm Hg without the appearance of orthostatic hypotension. Hypertrichosis and fluid retention did occur, with an average weight gain of 1.8 kg, concomitant with an increased plasma volume. Pulse rate and cardiac output increased; no significant changes were observed in plasma renin activity, renal plasma flow, glomerular filtration rate or excretion of catecholamines or aldosterone. Minoxidil appears to be a useful antihypertensive drug for treating patients who do not respond adequately to therapy with diuretic and beta adrenergic blocking agents.

Adult↗