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Complications of intramedullary rods in osteogenesis imperfecta: Bailey-Dubow rods versus nonelongating rods.

Twenty-nine patients with osteogenesis imperfecta underwent 108 intramedullary roddings with 42 Bailey-Dubow rods and 66 nonelongating rods. The average age at insertion of the first rod was 5 years; average follow-up was 3.1 years (range 1-9 years). The overall complication rate was 60%-69% for Bailey-Dubow rods and 55% for nonelongating rods. Forty-seven percent of bones receiving rods required reoperation. Nonelongating rods had a 29% reoperation rate and a 24% replacement rate; Bailey-Dubow rods had a 19% reoperation rate and a 12% replacement rate.

Adolescent

Transport properties of rigid bent-rod macromolecules and of semiflexible broken rods in the rigid-body treatment. Analysis of the flexibility of myosin rod.

The translational diffusion coefficients, rotational relaxation times and intrinsic viscosities of rigid bent rods, composed by two rodlike arms joined rigidly at an angle alpha, have been evaluated for varying conformation using the latest advances in hydrodynamic theory. We have considered semiflexible rods in which the joint is an elastic hinge or swivel, with a potential V(alpha) = 1/2Q alpha 2 with constant Q. Accepting the rigid-body treatment, we calculate properties of broken rods by averaging alpha-dependent values for rigid rods. The results are finally used to interpret literature values of the properties of myosin rod. Q is regarded as an adjustable parameter, and the value fitted is such that the average bending angle of myosin rod is approximately 60 degrees.

Mathematics

Rod-signal interneurons in the rabbit retina: 1. Rod bipolar cells.

The cellular morphology and topographic distribution of the rod bipolar cells in the rabbit retina have been investigated by selective labelling with protein kinase C-immunohistochemistry (Negishi et al., Neurosci, Lett. 94:247-252, 1988) and by Lucifer Yellow injection of microscopically identified cells in a superfused retinal preparation. The distribution of the rod bipolar cells parallels that of their input neurons, the rod photoreceptors, in that the rod bipolars reach maximum densities of 5,000-7,000 cells/mm2 on the inferior and superior flanks of the visual streak, dropping to slightly lower densities at the peak visual streak. The centre-to-periphery density gradient of the rod bipolars is about 2.5:1, and the density ratio of rods to rod bipolars shows little variation across the retina, ranging from 43:1 in superior retina to 58:1 in inferior retina. The dendritic field area of the rod bipolar cells increases from 600 microns2 on the visual streak to 1,200 microns2 in the far-superior retina, with each point on the retina overlapped by 2.5-3.5 dendritic fields. The axonal field area of the rod bipolar cells increases from about 100 microns2 at the peak visual streak to about 250 microns2 at the retina edge, and the axonal field coverage ranges from 0.55 in the visual streak to about 0.8 in peripheral retina. Although there appear to be gaps in the local array of rod bipolar somata, these areas are covered by the axonal arbours of neighbouring rod bipolar cells.

Animals

Abundant nuclear rods in adult-onset rod disease.

Abundant, highly organized, rod-shaped particles have been found in skeletal-muscle nuclei of two patients with adult-onset rod disease. They were usually single in affected nuclei. Like myofibrillar rods, the nuclear rods consisted of bundles of long, parallel, apparently cross-linked filaments. On longitudinal section the rods had an axial periodicity and in transverse section a wire-mesh appearance. Average periodicities were 189A (nuclear) and 178A (myofibrillar) axially, 180A (both) transversely between the longitudinal rod-filaments on longitudinal-section and cross-section of the rods. Minor differences were that the nuclear rods were slightly lighter stained after osmium-uranyl acetate-lead citrate, lacked thin filaments protruding from their ends, and often were broader. It is proposed that nuclear rods may have a contractile-protein composition and pathokinesis similar to that of myofibrillar rods. Their formation may reflect an epitomization of a newly recognized general biological capability of exogenous, or perhaps endogeneous, nuclear protein alteration.

Adult

Cancellation of rod signals by cones, and cone signals by rods in the cat retina.

1. The interaction of rod and cone signals at the level of cat retinal ganglion cells was studied by a method of light exchange. Two spectrally distinct lights were exchanged in such a manner that the rate of photon catch by rods increased in a stepwise manner at the same moment that the cone rate decreased in the same manner, and vice versa. 2. Under any conditions of adaptation, where both rods and cones contributed to the ganglion-cell discharge, it was always possible to adjust the ratio of the magnitudes of the rod and cone stimuli so that no change in ganglion-cell discharge could be detected by listening to the recorded activity via a loudspeaker. We term this condition a silent exchange. 3. On the face of it, the condition of silent exchange arises when rod and cone signals are able to cancel one another, when made opposite in phase by the exchange situation. But was this silence due to a true cancellation of the signals from one photoreceptor type by those of the other type, or was it due to our failure to stimulate the photoreceptors adequately? In order to test whether rod signals can cancel those of cones we bleached both visual pigments and set our exchange apparatus to stimulate the two photoreceptors in the antagonistic manner described above. At first no response could be heard on exchange, for the thresholds of both rods and cones lay above that of our apparatus. But the cones soon recovered and a strong response was heard on exchange. With no change in our stimulating situation, this response diminished with time and silence was again restored. This restoration of silence could not be due to the cones alone, for with time their sensitivity could only further increase. It could only be the increasing sensitivity of the rods that quietened the cone signals. In agreement with this conculsion, the dark-adaptation curve of the rods showed that they became sensitive to our stimulus at the time that the cones began to be silenced. 4. By means of coloured backgrounds we have also shown the converse, namely that rods signals can be cancelled by those of cones.

Animals

Receptive field organization of ganglion cells in the frog retina: contributions from cones, green rods and red rods.

1. The impulse discharge of ganglion cells was recorded with extracellular micro-electrodes in the excised and opened eye of the common frog, Rana temporaria. 2. When a single unit was isolated, the cell type was first determined according to the Maturana, Lettvin, McCulloch & Pitts (1960) classification with the aid of varying moving and stationary stimuli. 3. Class 4 cells respond only to a decrease of light when cones are stimulated but respond to an increase of light when green rods are stimulated. A distinct class of deviating class 4 cells was found that give a brief high frequency burst at 'off' from their small excitatory receptive fields (ERF); unlike typical class 4 cells they possess a purely inhibitory surrounding field (IRF).4. The contributions from the cones and the green and red rods were isolated by measuring the thresholds of the discharges with on-off stimuli of varying wave-lengths against strong yellow backgrounds, or against a very weak background or no background at all. The spatial distribution of the contributions to the ERF was determined by mapping threshold profiles, and additional information about ERF and IRF was obtained from area-threshold curves. 5. The cone-mediated ERFs were found to be 0-06-0-50 mm wide (1-5-12 degrees of visual field), which agrees well with the sizes of the dendritic trees of the ganglion cells. The green rod-mediated ERFs can be 0-5-1-5 mm wide and have less distinct boundaries than the cone-mediated. The green rod-mediated ERF of an individual ganglion cell is always larger than the cone-mediated ERF of the same cell. The red rod-mediated ERFs seem to be somewhat larger than the cone-mediated but smaller than the green rod-mediated. 6. The green rods contribute only to the on thresholds of class 1, 2 and 4 cells, but both to on and off in typical class 3 cells, while the cones contribute to on and off in classes 1-3 and only to off in class 4.7. When the red rods begin to contribute during dark adaptation they seem to enter the cone but not the green rod channels. 8. All three receptor types contribute to the IRF surrounding the ERF of classes 1, 2, 3 and deviating class 4 cells. Normal class 4 cells have no IRF. 9. The organization of the receptive fields is discussed in relation to the anatomy and electrophysiology of the cell types transmitting the signals from the receptors to the ganglion cells.

Action Potentials

Oscillations in rod and horizontal cell membrane potential: evidence for feed-back to rods in the vertebrate retina.

1. Rods and horizontal cells were studied with intracellular recordings in the retina of the toad, Bufo marinus; 161 cells were from the eyecup preparation and thirty were from the isolated perfused retina. 2. Of these cells, 39% exhibited either transient or sustained oscillations of membrane potential. Light flashes either evoked transient oscillations or temporarily abolished sustained oscillations. The amplitudes of the oscillations could be as large as 27 mV. The frequency of the oscillations at 25 degrees C was between 1-5 and 3-5 Hz and was strongly dependent on temperature and background illumination. 3. The rod oscillation amplitude and the peak of the horizontal cell light response increased similarly with increasing test flash diameters. They continued to grow for diameters much larger than those which increased the peak of the rod light response. 4. Perfusion of the isolated retina with 2 mM aspartate had only a small effect on the rod light response but it completely eliminated the horizontal cell light response as well as the oscillations recorded in both rods and horizontal cells. 5. It is believed that the oscillations result from a reverberating interaction between rods and neurones post-synaptic to rods. Thus, rods can be both post- as well as presynaptic retinal elements.

Adaptation, Ocular

Adult-onset rod disease with abundant intranuclear rods.

The third case of adult-onset rod disease (nemaline myopathy) with abundant myofibrillar as well as intranuclear rods is described. The 61-year-old woman suffered from progressive weakness of proximal extremities and of the neck, mimicking polymyositis. Muscle biopsy revealed a striking myopathic pattern, with intranuclear rods occurring in 31% of the fibres. On light and electron microscopy and by immunohistochemical study, the rods differed from myofibrillar rods. The absence of alpha-actinin in intranuclear rods suggests an enhanced readiness of actin filaments to bind to diverse proteins, instead of overproduction of alpha-actinin as the pathogenetic basis of the rod formation.

Actinin

Influence of rod adaptation upon cone responses to light offset in humans: II. Results in an observer with exaggerated suppressive rod-cone interaction.

In normal observers, sensitivity of cones to rapid sinusoidal flicker decreases by about 0.7 log units as rods progressively dark adapt. However, Arden and Hogg (1985) described a night-vision disorder characterized by normal rod sensitivity but exaggerated suppressive rod-cone interaction (SRCI). We refer to this condition as the exaggerated SRCI syndrome (ESS). The present paper examines the influence of rod-adaptation upon cone-mediated responses to light onset and offset in an observer with ESS. Under all conditions of adaptation examined, sensitivity of cones to rapid-on waveforms is indistinguishable to that of a normal observer tested under identical circumstances; rod sensitivity is also normal. However, the sensitivity of cones to transient decreases in illumination is clearly subnormal under light-adapted conditions. This deficit in cone responsiveness to light offset becomes increasingly subnormal as rods dark adapt and, when completely dark adapted, the ESS observer is nearly blind to 1 Hz rapid-off sawtooth waveforms. These results strongly bolster previous results that suggest that suppressive rod-cone interaction is restricted to the response to transient decreases in illumination.

Adaptation, Ocular

Rod visual fields in cone-rod degeneration. Comparisons to retinitis pigmentosa.

Dark-adapted visual fields to short- and long-wavelength stimuli were obtained from 20 patients with cone-rod degeneration, 20 patients with retinitis pigmentosa, and ten normal subjects. Patients were selected because they retained rod electroretinographic (ERG) function over a sufficient range for the Naka-Rushton analysis of retinal illuminance versus amplitude functions. Patients with cone-rod degeneration retained a relatively normal field topography although overall sensitivity was reduced. The mean sensitivity loss was consistent with a small elevation in ERG semisaturation constant and minimally delayed rod b-wave implicit times. Rod visual fields from patients with retinitis pigmentosa retaining rod ERG function were consistent with log sensitivity profiles reported previously for type 2 patients. Sensitivity loss was greatest in midperipheral regions, with most patients showing least loss in the far periphery. Disproportionate loss in the midperiphery is consistent with a large elevation in the ERG semisaturation constant and prolonged rod b-wave implicit times.

Adolescent

Rod-rod interaction in the retina of the turtle.

Intracellular responses were recorded from rods in isolated eye-cups of the snapping turtle, Chelydra serpentina. Responses to small and large diameter spots of 500 nm light were studied. 1. The peak amplitudes of responses smaller than approximately 2 mV were directly proportional to irradiance. Small spots (less than 100 mum diameter) produced approximately 30 muV/rhodopsin molecule bleached. Increasing stimulus diameter to 400-500 mum increased this five to seven times to about 200 muV/rhodopsin molecule bleached in the impaled receptor. The difference is attributed to a neural "enhancement" produced by stimulating neighbouring rods. 2. Enlarging the diameter of a spot altered the shape of responses produced by very dim lights. 3. The variance of responses to a small spot was only slightly less than the mean. The variance of responses to a large spot was much less than the mean. 4. Responses evoked by a small spot of dim light obeyed the superposition principle in that the response to a very dim step of light was the integral of the response of a very dim flash. Responses evoked by a large spot did not obey the superposition principle. The response to a step of dim light covering a spot of large diameter was less than predicted from the integral of the response to a flash. The difference is attributed to a neural "disenhancement" produced by stimulating neighbouring rods. 5. The time course of this disenhancement could be observed by presenting two large diameter, dim flashes within a short interval. The time course of disenhancement did not coincide with that of the voltage response but was delayed such that its maximum occurred after the peak amplitude. 6. Dim background lights of different diameter, which delivered the same quantity of light to the impaled cell but very different quantities of light to neighbouring cells, left the response produced by a small diameter test spot unaltered. It is concluded that rod-rod interaction can modify the intracellular responses of rods in two ways; it produces an early enhancement which increases response amplitude nearly tenfold and also a delayed disenhancement which replaces the wave of enhancement that follows a flash.

Animals

The trajectory of a stiff rod in a curved potential energy trough. An initial result for short nucleosomal rods.

The equilibrium trajectory of the axis of a rod subject to an externally imposed curved potential energy trough tends to conform to the shape of the curved trough, but also tends to be straight because of elastic resistance to bending. The actual path of the axis is a balance between the two extremes. We consider a potential energy trough centered along a circular arc of radius R. For a rod of small length compared to R, we show that the axis at equilibrium forms an arc of a circle of radius greater than R. The value of the radius of the axial path depends on the relative values of the Hooke's Law bending constant for the rod and the depth and width of the trough. Motivation for the calculation is provided by nucleosomal DNA, which conforms to the surface of a roughly cylindrical histone core at physiological ionic strength, but is observed to unwind into a partially extended conformation at very low ionic strength. We suggest that the rigidity to bending of short DNA segments becomes sufficiently great at low ionic strength to overcome attractive interactions with the histone surface. Alternately, of course, if during the cell cycle mutually attractive forces between DNA and histone core are weakened at constant ionic strength, the same type of unfolding would be expected to occur as the strength of the DNA-histone contacts drops below the level required to overcome elastic resistance to bending of the DNA rod.

Animals

Metabolic labeling of rod outer segment phospholipids in miniature poodles with progressive rod-cone degeneration (prcd).

The recessive genetic defect in miniature poodles which results in progressive rod-cone degeneration (prcd) has been investigated in an attempt to determine the biochemical abnormality involved. In the present study, the rod outer segments of young prcd affected miniature poodles and normal dogs have been compared with respect to the incorporation of intravitreally injected [3H]palmitic acid. [14C]linolenic acid, and [14C]docosahexaenoic acid into neutral lipids and phospholipids as well as [3H]palmitate and [14C]leucine into rhodopsin. In addition, 3 mm trephined punches of retinas were incubated with [3H]palmitic acid, [3H]arachidonic acid, [14C]linolenic acid, [3H]serine, [14C]glycerol and [14C]leucine. No difference in incorporation of labeled precursors into lipids or rhodospin was noted between prcd affected and normal retinas. Phosphatidyl choline appeared to function as a carrier of fatty acids to the rod outer segment where they were redistributed to other phospholipids. An interesting lack of conversion of the essential fatty acid linolenic acid to docosahexaenoic acid was noted in both normal and affected retinas. This conversion involves elongation and desaturation of linolenic acid and may take place primarily in extraretinal tissues such as the liver. This finding, in conjunction with a parallel study of plasma fatty acids which has shown significantly lower levels of docosahexaenoic acid in prcd affected poodles, points to a possible systemic defect in the metabolism or transport of docosahexaenoic acid, a fatty acid uniquely enriched in the photoreceptor outer segments.

Animals

Transmission measurements in multi-rod arrays: a design study for a multi-rod collimator.

The results of transmission measurements for neutrons, cobalt-60 gamma-rays, and 10 and 15 MV photons made with close-packed arrays of tungsten rods are presented. These results indicate that tungsten rod arrays of reasonable thickness can provide for primary or secondary collimation of all these radiation beams. Development work on a collimation system utilizing the multi-rod concept which is capable of producing irregularly shaped fields and suitable for use in photon or neutron radiation therapy is described.

Humans

Beta-lactamase in gram-negative rods: the relationship between penicillinase and R plasmids in gram-negative rods.

Concomitant with the extensive use of antibiotics, the number of multiple antibiotic-resistant strains has been increasing. Since resistance is mainly mediated by R plasmids, we undertook to investigate the characteristics of R plasmid-determined beta-lactamase in 6 Gram-negative rods. The beta-lactamase produced by each organism was classified by its substrate: type P which attacks penicillins, type C which attacks cephalosporins, and type C/P which attacks both penicillins and cephalosporins. Though the chromosomally mediated beta-lactamase of almost all Gram-negative rods is classified as type C, R plasmid-mediated beta-lactamase is almost equally active against both penicillins and cephalosporins. Therefore, we suggest that type C/P beta-lactamase was mediated by R plasmids in Gram-negative rods which already produced chromosomally mediated type C beta-lactamase. The strains which produced type C/P beta-lactamase tended to be more resistant to antibiotics than the other beta-lactamase producing strains. Among type C/P strains, the sensitivity to cephalosporins varied with the bacterial species, whereas all these strains were highly resistant to penicillins. Even for piperacillin, which is stable to cephalosporinase, the MIC at which the cumulative percentage of strains inhibited was 50% (MIC50) was over 50 micrograms/ml in all strains tested.

Cefazolin

Noncatalytic cGMP-binding sites of amphibian rod cGMP phosphodiesterase control interaction with its inhibitory gamma-subunits. A putative regulatory mechanism of the rod photoresponse.

The cGMP phosphodiesterase (PDE) of retinal rods plays a central role in phototransduction. Illumination leads to its activation by a rod G-protein (Gt, transducin), thus causing a decrease in intracellular cGMP concentration, closure of plasma membrane cationic channels gated by cGMP, and development of the photoresponse. The PDE holoenzyme is an alpha beta gamma 2 tetramer. The alpha- and beta-subunits each contain one catalytic and one, or possibly two, noncatalytic cGMP-binding sites. Two identical gamma-subunits serve as protein inhibitors of the enzyme. Their inhibition is removed when they bind to Gt-GTP during PDE activation. Here we report that the noncatalytic cGMP-binding sites regulate the binding of PDE alpha beta with PDE gamma and as a result determine the mechanism of PDE activation by Gt. If the noncatalytic sites are empty, Gt-GTP physically removes PDE gamma from PDE alpha beta upon activation. Alternatively, if the noncatalytic sites are occupied by cGMP, Gt-GTP releases PDE gamma inhibitory action but remains bound in a complex with the PDE heterotetramer. The kinetic parameters of activated PDE in these two cases are indistinguishable. This mechanism appears to have two implications for the physiology of photoreceptor cells. First, the tight binding of PDE gamma with PDE alpha beta when the noncatalytic sites are occupied by cGMP may be responsible for the low level of basal PDE activity observed in dark-adapted cells. Second, occupancy of the noncatalytic sites ultimately controls the rate of PDE inactivation (cf. Arshavsky, V. Yu., and Bownds, M. D. (1992) Nature 357, 416-417), for the GTPase activity that terminates PDE activity is slower when these sites are occupied and Gt stays in a complex with PDE holoenzyme. In contrast GTPase acceleration is maximal when the noncatalytic sites are empty and Gt-PDE gamma dissociates from PDE alpha beta. Because cGMP levels are known to decrease upon illumination over a concentration range corresponding to the binding constants of the noncatalytic sites, the binding might be involved in determining the lifetime of activated PDE, after a single flash and/or during dark adaptation.

3',5'-Cyclic-GMP Phosphodiesterases

Rod-cone dystrophy associated with a rod system electroretinogram obtained under photopic conditions.

A 14-year-old girl with a history of night blindness and poor visual acuity was examined. Cystic-appearing lesions were apparent in the fovea, and pigmentary changes were observed in the midperipheral retina. Electroretinograms (ERGs) recorded from the dark- and light-adapted eye were similar in waveform, implicit time, and approximate amplitude. Results of examination of the spectral characteristics of the light-adapted ERG demonstrated that the recordings represented activity of the rod system, despite the presence of a background field, which eliminates the response of the rod system in normal subjects.

Adaptation, Ocular

Electron microscope study of the rod-to-coccus shape change in a temperature-sensitive rod- mutant of Bacillus subtilis.

The changes in cell morphology of Bacillus subtilis rodB during a temperature shift from 20 to 42 degrees C, in the absence of added anions, are described. At 20 degrees C the organisms grow as rods but gradually become spherical in shape when placed at 42 degrees C. The shape change is initiated by an increase in diameter at the cell equator, resulting in a bulged morphology, which is further modified to the morphology of a coccus. This change may involve a modification of the pattern of normal cylindrical extension such that incorporation of newly synthesized wall leads only to increase in diameter, perhaps from a growth zone of limited extent. The pattern of surface growth was followed by reconstructing the sequence of cross wall formation and pole construction in rods grown at 20 degrees C and in organisms incubated at 42 degrees C for 75 and 150 min. In thin section, wall forming the septum and nascent poles can be distinguished from the surface distal to the division site by the presence of raised tears, perhaps analogous to the wall bands of streptococci. By using an analog rotation technique involving the three-dimensional reconstruction of cells by mathematical rotation of axial thin sections about their longitudinal axis, it is shown that the proportion of septal wall increases during the shape change. In the coccal forms, all surface growth may arise from septal growth sites.

Bacillus subtilis