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Effects of indomethacin on spacing of conceptuses within the uterine horn and on fetal and placental growth in the rat.

In the rat, as in most other polytocous species, fetuses tend to be relatively evenly spaced along the uterine horn, perhaps to minimize possible effects of local overcrowding on placental function and fetal growth. Here we administered 2 mg of indomethacin, in split doses on day 5 of gestation, in an attempt to disturb evenness of spacing and so reveal local overcrowding effects, if any. The effects on spacing, expressed as the coefficient of deviation of distances between neighboring implants (CVd%) and correlations between fetal and placental weights and distance to neighbors, was examined on day 16 and day 22 of gestation to cover the period of rapid fetal growth. Indomethacin markedly affected evenness of spacing; at day 16, CVd% increased from a control value of 19.2 to 50.8% and at day 22 from 27.5 to 41.2%. Despite the increased variability of spacing and consequent local crowding, including examples of conjoined placentas in the treated rats, there was no evidence that these local factors affected placental growth or weight of individual fetuses. Indomethacin, however, had a general effect on placental and fetal growth. At day 16, mean fetal weights were retarded but by day 22 had caught up to those of control litters, and this was accompanied by significant placental hypertrophy. Collectively, these results show that the uterus has sufficient reserve to cope with relatively uneven spacing of fetuses and have provided a model for examining catch-up growth of fetuses and accompanying placental changes.

Animals↗

The lateral view radiograph for assessment of the tibiofemoral joint space in knee osteoarthritis: its reliability, sensitivity to change, and longitudinal validity.

OBJECTIVE: To evaluate the reliability, validity, and sensitivity to change of tibiofemoral (TF) narrowing on lateral radiographic views. METHODS: In a natural history study of symptomatic knee osteoarthritis (OA), both lateral view and fluoroscopically positioned posteroanterior (PA) semiflexed view radiographs of the knee in 30 degrees of flexion and with weight bearing were obtained at baseline and at 30 months. Test-retest reliability was evaluated using repeat radiographs, with joint space width measured using electronic calipers. All radiographs were scored on a 0-3 scale, and progression of joint space loss was defined as narrowing of the joint space by 1 grade. We evaluated sensitivity to change compared with the PA view. We evaluated validity by examining whether knees with progression showed expected malalignment on full-limb films. RESULTS: Test-retest reliability of the TF joint space using the lateral view had a root mean square error of 0.303 mm, with 92.5% of repeats within 1 mm. More knees showed progression on the lateral view alone (n = 41) than on the PA view alone (n = 27). Compared with knees without joint space loss, knees with medial compartment loss on the lateral view only were more varus malaligned (P < 0.001), while those with lateral compartment loss were more valgus malaligned (P = 0.008). CONCLUSION: In the assessment of TF joint space loss, lateral view radiographs are reliable, valid, and more sensitive to change than fluoroscopically positioned PA radiographs.

Cartilage, Articular↗

Space-time clustering of childhood cancer in great Britain: a national study, 1969-1993.

Previous studies have provided evidence that infections may play a part in the aetiology of certain childhood cancers. The finding of space-time clustering indicates the presence of an environmental component to aetiology and is especially supportive of a role for infections. Space-time clustering occurs when excess numbers of cases of a disease are observed within small geographical locations at limited periods of time and this cannot be explained in terms of general excesses in those locations or at those times. To investigate whether infections may be involved in the aetiology of childhood cancer, we have analysed for space-time clustering using a large set of national population-based data from Great Britain for the period 1969-1993. Data were examined by a second-order procedure based on K-functions, with fixed thresholds of closeness in space (0.5-7.5 km) and closeness in time (0.1-1.5 years). Locations were addresses at diagnosis. Tests were repeated, replacing geographical distances with distances to the 19th-33rd nearest neighbours and this provided the primary result for each analysis. There were a total of 32,295 cases of childhood cancer. The analyses showed statistically significant evidence of space-time clustering for acute lymphoblastic leukaemia over the whole age range (p = 0.04), but especially for ages 1-4 years (p = 0.03). There was less statistically significant evidence for total leukaemia (p = 0.048). Significant space-time clustering was also evident for soft tissue sarcomas (p = 0.03) and osteosarcomas (p = 0.02). Results support other evidence suggesting a role for infections in the aetiology of these particular diagnostic groups.

Adolescent↗

Accurate d-spacings from zero-order Laue zone patterns.

Experimental d-spacing values are criteria towards the identification of crystallites by electron diffraction. Conclusive identifications often rely on accurate d-spacings. It is shown here that accurate orthogonal components (in mm) for the primitive unit vectors of a zero-level diffraction pattern can be obtained through least-squares processing of (x,y) coordinates for all spots on the film. Valid vectors from the origin spot to any spot in the plane of the film are integer linear combinations of the two selected unit vectors. Accurate lengths and standard deviations for such vectors therefore can be calculated from the least-squares results. Corresponding d-spacings can then be calculated from the vector lengths on the film and the camera constant. In order to obtain d-spacing values that are not only precise, but also accurate, an accurate value of the camera constant should be used. This requires calibration of the experimental setup with reference materials in the same experimental conditions, with careful control of the sample height. For the same quality of measurements, the improvement in the accuracy of the d-spacings obtained with the proposed method is approximately proportional to the square root of the number of measurements taken. Practically, typical improvement in accuracy is about threefold, and accuracies of a fraction of a percent in d-spacings are achievable in this way. The above approach has been programmed as an option in the NRCBED program.

Crystallization↗

K-space in the clinic.

Magnetic resonance imaging (MRI) sequences are characterized by both radio frequency (RF) pulses and time-varying gradient magnetic fields. The RF pulses manipulate the alignment of the resonant nuclei and thereby generate a measurable signal. The gradient fields spatially encode the signals so that those arising from one location in an excited slice of tissue may be distinguished from those arising in another location. These signals are collected and mapped into an array called k-space that represents the spatial frequency content of the imaged object. Spatial frequencies indicate how rapidly an image feature changes over a given distance. It is the action of the gradient fields that determines where in the k-space array each data point is located, with the order in which k-space points are acquired being described by the k-space trajectory. How signals are mapped into k-space determines much of the spatial, temporal, and contrast resolution of the resulting images and scan duration. The objective of this article is to provide an understanding of k-space as is needed to better understand basic research in MRI and to make well-informed decisions about clinical protocols. Four major classes of trajectories-echo planar imaging (EPI), standard (non-EPI) rectilinear, radial, and spiral-are explained. Parallel imaging techniques SMASH (simultaneous acquisition of spatial harmonics) and SENSE (sensitivity encoding) are also described.

Artifacts↗

Single-shot half-Fourier RARE sequence with ultra-short inter-echo spacing for lung imaging.

PURPOSE: To improve the image quality of pulmonary magnetic resonance (MR) imaging using an ultra-short inter-echo spacing half-Fourier single shot rapid acquisition with relaxation enhancement (USHA-RARE) sequence. MATERIALS AND METHODS: Pulmonary MR images were acquired by USHA-RARE sequence with various inter-echo spacings. The sequence parameters were as follows: repetition time (TR)/effective TE: infinite/39-41 msec; section thickness: 10 mm; acquisition matrix: 128 x 128; field of view: 450 x 450 mm. Inter-echo spacing varied (2.5 msec, 3.0 msec, 3.5 msec, 4.0 msec, 4.5 msec, 5.0 msec), and the respective phase-encoding steps were 80, 77, 75, 74, 73, and 72. Signal-to-noise ratios (SNRs), the signal ratios between lung and fat (lung-to-fat ratio: LFRs), and the signal ratios between the lung and the serratus anterior muscle (lung-to-muscle ratio: LMRs) of each inter-echo spacing were calculated, and statistically evaluated. RESULTS: The SNRs at inter-echo spacings of < or = 3.0 msec were significantly higher than those > or = 4.0 msec (P < 0.05). The LFRs and LMRs at inter-echo spacing < or = 3.0 msec were significantly higher than those > or = 4.0 msec (P < 0.05). CONCLUSION: USHA-RARE sequence does improve signal intensity from the lung.

Adult↗

Feature space analysis of MRI.

This paper presents an MRI feature-space image-analysis method and its application to brain tumor studies. The proposed method generates a transformed feature space in which the normal tissues (white matter, gray matter, and CSF) become orthonormal. As such, the method is expected to have site-to-site and patient-to-patient consistency, and is useful for identification of tissue types, segmentation of tissues, and quantitative measurements on tissues. The steps of the work accomplished are as follows: (1) Four T2-weighted and two T1-weighted images (before and after injection of gadolinium) were acquired for 10 tumor patients. (2) Images were analyzed by an image analyst according to the proposed algorithm. (3) Biopsy samples were extracted from each patient and were subsequently analyzed by the pathology laboratory. (4) Image-analysis results were compared with the biopsy results. Pre- and postsurgery feature spaces were also compared. The proposed method made it possible to visualize the MRI feature space and to segment the image. In all cases, the operators were able to find clusters for normal and abnormal tissues. Also, clusters for different zones of the tumor were found. The method successfully segmented the image into normal tissues (white matter, gray matter, and CSF) and different zones of the lesion (tumor, cyst, edema, radiation necrosis, necrotic core, and infiltrated tumor). The results agreed with those obtained from the biopsy samples. Comparison of pre- with postsurgery and radiation feature spaces illustrated that the original solid tumor was not present in the second study, but a new tissue component appeared in a different location of the feature space. This tissue could be radiation necrosis generated as a result of radiation.

Artifacts↗

Assessment of axonal fiber tract architecture in excised rat spinal cord by localized NMR q-space imaging: simulations and experimental studies.

NMR q-space imaging is a method designed to obtain information from porous materials where diffusion-diffraction phenomena were observed from which pore size was derived. Recently, the technique has been applied to the study of biological structures as well. Although diffusive diffraction has so far not been observed in multicellular systems, displacement profiles have been used with some success as a means to estimate structure size. However, there have been no quantitative correlations of the retrieved structure sizes with histology. Clearly, the complexity of tissue architecture poses significant challenges to the interpretation of q-space data. In this work, simulations were first performed on a two-compartment model to demonstrate the effects of interference of the diffraction patterns arising from intra and extra-axonal compartments and finite boundary permeability on q-space data. Second, q-space echo attenuation was simulated on the basis of histologic images of various rat spinal cord fiber tracts and the information obtained from the displacement profiles were compared with structural parameters computed from the histologic images. The results show that calculated mean displacements and kurtosis parallel mean axon size and axonal density. Finally, spatially localized q-space measurements were carried out at the locations where simulations had previously been performed, resulting in displacement data that support those obtained by simulation. The data suggest the NMR q-space approach has potential for nondestructive analysis of the axonal architecture in the mammalian spinal cord.

Animals↗

Undersampling k-space using fast progressive 3D trajectories.

In 3D MRI, sampling k-space with traditional trajectories can be excessively time-consuming. Fast imaging trajectories are used in an attempt to efficiently cover the k-space and reduce the scan time without significantly affecting the image quality. In many applications, further reductions in scan time can be achieved via undersampling of the k-space; however, no clearly optimal method exists. In most 3D trajectories the k-space is divided into regions that are sampled with shots that share a common geometry (e.g., spirals). A different approach is to design trajectories that gradually but uniformly cover the k-space. In the current work, successive shots progressively add sampled regions to the 3D frequency space. By cutting the sequence short, a natural undersampled method is obtained. This can be particularly efficient because in these types of trajectories the contribution of new information by later shots is less significant. In this work the performance of progressive trajectories for different degrees of undersampling is assessed with trajectories based on missile guidance (MG) ideas. The results show that the approach can be efficient in terms of reducing the scan time, and performs better than the stack of spirals (SOS) technique, particularly under nonideal conditions.

Algorithms↗

Partial-k-space acquisition method for improved SNR efficiency and temporal resolution in 3D fMRI.

Previous studies have shown the relative importance of physiological noise and thermal noise in 2D MR images. Since physiological noise is proportional to the signal, it can be the dominant component at the center of k-space. In this study we demonstrate that the signal-to-noise ratio (SNR) efficiency and temporal resolution for 3D functional MRI (fMRI) are increased by the use of a partial-k-space acquisition method. In partial-k-space methods, the high-spatial-frequency components are doubled in amplitude during reconstruction, resulting in twice as much noise from those components. However, in sum these contributions are relatively small compared to those at the low spatial frequencies, where physiological noise is dominant. Therefore, the effect on the final MR images is almost negligible due to the square summation rule. Thus, the partial-k-space 3D method sacrifices much less SNR than is expected from the thermal noise model, and the SNR efficiency is increased compared to a full-k-space acquisition since more time frames can be collected for the same scan time. Accordingly, the temporal resolution can be increased in 3D acquisitions because only partial coverage of k-space is necessary. Experimental results confirm that more activation with a higher average t-score is detected by this method.

Algorithms↗

Cyclosporine treatment promotes survival of human fetal neural retina transplanted to the subretinal space of the light-damaged Fischer 344 rat.

We have reported that xenografts of human fetal neural retina survive in the subretinal space of cyclosporine-immunosuppressed rats. In view of the current controversy regarding the role of cyclosporine, we wished to determine if cyclosporine immunosuppression was an absolute requirement for retinal xenograft survival. Neural retinas from human fetal eyes obtained within 1 h of termination of pregnancy were stored in Optisol medium (Chiron Vision, Irvine, CA) at 4 degrees C for 2 and 7 days. Retinas were then transplanted to the subretinal space of either cyclosporine-treated (10 mg/kg/day) light-damaged Fischer 344 rat eyes (17 animals, 28 eyes) or to the subretinal space of light-damaged Fischer 344 rat eyes (9 animals, 15 eyes) receiving no cyclosporine treatment. Grafted eyes were observed clinically at 10, 20, and 30 days posttransplantation. At 30 days, the animals were sacrificed and the grafts observed histologically. Human fetal retina xenografted to the subretinal space of immunosuppressed rats survived (9/17 animals, 12/28 eyes), showed good integration with the host retina and initial photoreceptor differentiation. Tissue xenografted to the subretinal space of non-cyclosporine-treated rats was not observed to survive (0/9 animals, 0/15 eyes). A low level cellular reaction was seen around three of the injection sites within the nonimmunosuppressed rats. We conclude that immunosuppression is necessary for the survival of human fetal neural retina xenografted to the subretinal space.

Animals↗

Cooperative DNA-protein interactions. Effects of changing the spacing between adjacent binding sites.

Cooperative binding of specific DNA-binding proteins plays crucial roles in gene regulatory circuitry, and is a model system for interactions between proteins bound to DNA. We have studied coliphage HK022 repressor, which binds to two adjacent operators with a cooperativity parameter of approximately 2000. We examined the effect of changing the spacing between these two operators on cooperativity and on the conformation of the complex. Maximum cooperativity was seen with the wild-type spacing; considerable cooperativity was retained for most spacing variants, but was abolished when the operators lay on opposite faces of the DNA helix. Most spacing variants conferred changes in the conformation of the DNA-protein complex. Our data indicate that the pairwise cooperativity observed with the wild-type spacing results from a conformation that prevents protein-protein contacts with flanking bound dimers. We conclude that protein-DNA complexes involving the same specific binding sites and the same protein molecules can adopt many different conformations, depending on the spacing between the binding sites. This conclusion may be broadly applicable to protein-DNA interactions in other systems.

Allosteric Regulation↗

The effect of nucleosome phasing sequences and DNA topology on nucleosome spacing.

The distances between the nucleosomes in eukaryotic chromatin that define the nucleosome repeat length are not universally constant, but vary between different cell types and activity states. We have previously established in a cell-free system that nucleosome spacing is essentially governed by electrostatic principles, most likely through charge neutralisation of linker DNA by cations either free in solution or on flexible histone domains. On the basis of the tight correlation between the parameters that affect nucleosome spacing and those that influence the folding of the nucleosomal fiber into higher order structures, we suggested that there is an intimate relationship between nucleosome spacing and chromatin folding. Here we describe DNA topology as a new parameter that influences nucleosome spacing in a predictable way. The effects of topology and cation concentrations integrate to define the final repeat length. The phenomenon of "nucleosome phasing" describes nucleosomal arrays that are generated through positioning of nucleosomes by the underlying DNA sequence. To determine the relative contribution of DNA sequence and the parameters intrinsic to physiological chromatin for nucleosomal positions, we created situations where these two principles were in conflict. We found that nucleosome repeats directed by a strong positioning sequence are dominated by the cation-induced spacing as well as by the effects of topology. We conclude that the DNA sequence effects nucleosome spacing only by "fine tuning" of nucleosome positions within the framework of a repeat pattern that is established by other principles.

Animals↗

Navigating a set of discrete regions in body position space.

This paper defines a mathematical object that expresses physiological aspects of motor control, besides physical aspects. Based on observations in human development and rehabilitation, this paper lays a foundation for unifying discrete with continuous aspects of motor control. Discreteness in motor control arises from the fact that movements are planned by the organism, based on movement limits set by the organism, the task, and the environment, rather than following simply from physical laws. This paper defines two relations, an ordering and a contiguity relation, between discrete regions of joint space crossed with physical space, to make a d-space. Within the d-space, a particular body and physical position is represented by a completely ordered set, a coincidence. A trajectory through a continuous space is represented by a coincidence sequence. Examples are drawn mostly from human locomotion, with particular interest in balance. Only in certain regions of body and physical position space can a body maintain balance, for example, a standing human. Slow steps proceed from one balanced region to another. A poset (partially ordered set) of sets of steps and its relationship to a person's balance regions can be used in the study of development or rehabilitation.

Humans↗

Long-lasting and context-specific freezing preference is acquired after spaced repeated presentations of a danger stimulus in the crab Chasmagnathus.

A visual danger stimulus elicits an escape response in the crab Chasmagnathus that declines after repeated presentations. Previous results report that such waning may be retained as context-signal memory (CSM) or signal memory (SM): CSM is long lasting, associative, and produced by spaced training, while SM is an intermediate memory, nonassociative, and produced by massed training. The performances of both spaced and massed trained crabs are here examined, using video analysis to determine topographic changes in the behavioral response during and after training. During spaced training, escape vanishes and is mainly replaced by freezing, while during massed training, escape decreases over trials without being replaced by any defensive response. After 24 h, the marked proclivity to freezing persists in spaced trained crabs, while a high level of escaping is shown by massed trained crabs. The long-lasting freezing preference of spaced trained crabs proves to be context-specific and apparent from the very first presentation of the danger stimulus at testing, though freezing is not triggered by the sole exposure to the context. We conclude (a) that freezing preference is the acquired response of the CSM process; (b) that CSM can be properly categorized as an instance of contextual conditioning and SM of classical habituation; (c) that CSM and SM are not two phases of a memory processing but two distinctly types of memory; and (d) that therefore, the temporal distribution of training trials has a drastic effect on crab's memory, more dramatic than that previously described. The possibility that massed and spaced presentations of the same stimulus may represent two different stimulus types is discussed.

Animals↗

Diminished space in the acromioclavicular joint in forced arm adduction as a radiographic sign of degeneration and osteoarthrosis.

The purpose of this study was to examine the acromioclavicular joint by radiography under forced arm adduction to demonstrate diminished joint space as a sign of cartilage degeneration and osteoarthrosis. A total of 192 right and left joints were investigated in 96 healthy working men. There were three main results from the manoeuvre: in 135 of the 192 joints the space was reduced, in 33 joints it was unchanged, and in 24 joints the joint space was increased. In 43 joints (22% of the total) a marked reduction of the joint space to 1 mm or less occurred during the manoeuvre; in the remaining 92 joints with space reduction the reduction was less pronounced. A narrow acromioclavicular joint space during forced adduction of the arm indicates cartilage thinning and may be interpreted as a sign of osteoarthrosis.

Acromioclavicular Joint↗

Removal of cellular debris formed in the Disse space in patients with cholestasis.

Using electron microscopy, we investigated how cellular debris, formed in the Disse space during cholestasis, was cleared. Ten patients with cholestasis of varied origin and severity were studied and compared with 10 controls without liver disease. In cholestatic patients, sinusoidal cells contained variable amounts of amylase PAS-positive material. In clean perfusion-fixed sinusoids the endothelial cells often appeared swollen and active, with few fenestrations. Hepatocyte blebs and cellular debris were sometimes seen in the Disse space. Two mechanisms were apparently involved in the clearing process: phagocytosis by macrophages either infiltrated into the Disse space, or forming the barrier; and the passage of debris from the Disse space into the sinusoidal lumen through the endothelial wall. Debris was either forced through enlarged pores or through the wall, with a progressive invagination followed by an outpouching in the lumen. The force, possibly provided by endothelial massage, may not be sufficient to push out cellular debris from the Disse space; morphological data seemed to indicate that endothelial damage may be a necessary factor. Debris present in the lumen was phagocytized by numerous active macrophages. Cellular debris was not observed in the Disse space of control patients.

Adult↗

Assessment of the space for the lower wisdom teeth. Panoramic radiography in comparison with computed tomography.

From 13 patients a computed tomograph (CT-scan) and a panoramic radiograph (Orthophos, program 1, P1) were examined with respect to the spatial conditions of the lower wisdom teeth. In the panoramic radiograph the available space for the third molars of the lower jaw was determined by calculating the ratio (Q) of 2 distances: the mesiodistal crown diameter and the retromolar space. In the axial CT 3 different positions of the third molar were distinguished: third molar located anterior to the ramus mandibulae = sufficient space, partially within the ramus = restricted space, totally within the ramus = deficient space. These positions were compared with the findings in the panoramic radiograph, firstly in relation to the ramus and secondly in relation to a line (L) perpendicular to the occlusal plane at the intersection of the anterior border of the ramus and the crista temporalis. Furthermore, the mesial rotation of the third molar was measured and the relation of the bony structures surrounding the teeth were described. Comparison of the CT results with the quotients of the P1 showed that, for those wisdom teeth molars with an available space above 50% to under 100%, any of the 3 CT gradings was found. Assessing the projection of the ramus over the third molar as seen in the P1, 60% of the P1- and CT-results corresponded. The relation between the line L and the third molar showed coincidence in 76% of all cases. These results and the mesial rotation of the wisdom teeth as well as their different relation to the bony environment are possibly important factors concerning their eruption prognosis. The three-dimensional CT-scan gives new possibilities for further investigations of third-molar problems.

Adolescent↗