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PubMed2001

Experimental transplantation of autologous iris pigment epithelial cells to the subretinal space.

PURPOSE: To investigate the cellular morphology in the subretinal space following transplantation of iris pigment epithelial (IPE) cells from the same eye. METHODS: Following an iridectomy, fresh IPE cells were prepared and no culturing performed. After pars plana vitrectomy, a suspension of autologous IPE cells was injected into the subretinal space in 37 rabbits. The grafts were monitored by ophthalmoscopy and colour fundus photography. Rabbits were sacrificed at 1, 2, 3 and 6 months, respectively, and the eyes examined with light and electron microscopy. RESULTS: The grafted area retained the same configuration over 6 months but then appeared less pigmented. At 1-3 months, the IPE formed one or more contiguous layers on top of native RPE. At 6 months, cells compatible with grafted IPE were present in the subretinal space, often forming monolayer-like chains integrating with the native RPE. Depigmented cells of presumed IPE origin were seen and frequently in association with abundant melanin granules located in the apical portion of adjacent RPE cells. In such areas, large macrophage-like cells were observed. CONCLUSION: Transplanted IPE cells survived for up to 6 months in the subretinal space. Our observations suggest a scenario of remodelling of the cellular layers in the subretinal space over time where grafted IPE cells formed a compound layer with the native RPE. Transplantation of autologous IPE cells may have a potential as a treatment modality in selected cases of age-related macular degeneration.

Animals↗
PubMed2002

Coding of far and near space during walking in neglect patients.

Previous studies have shown that far space can be remapped as near when reached by a stick that artificially prolongs the participants' personal space. In the present study, the authors asked whether a similar remapping occurs when far space is reached not by using a tool but by locomotion. Neglect patients showed more severe neglect in far than in near space in bisection tasks executed from different distances either by pointing to a target line with a projection light pen or by walking across the line. A kinematic study of the walking performance of one of those neglect patients showed that, contrary to the prediction of remapping during locomotion, the walking trajectories were rectilinear. The authors interpreted these results as evidence that in their patients-at least for short, linear trajectories-no remapping of space took place during locomotion. The location of far objects was coded at the beginning of the movement, and the error in the bisection computation was generated within the 1st representation that was activated.

Adolescent↗
PubMed2000

Explanation for fracture spacing in layered materials

The spacing of opening-mode fractures in layered materials--such as certain sedimentary rocks and laminated engineering materials--is often proportional to the thickness of the fractured layer. Experimental studies of this phenomenon show that the spacing initially decreases as extensional strain increases in the direction perpendicular to the fractures. But at a certain ratio of spacing to layer thickness, no new fractures form and the additional strain is accommodated by further opening of existing fractures: the spacing then simply scales with layer thickness, which is called fracture saturation. This is in marked contrast to existing theories of fracture, such as the stress-transfer theory, which predict that spacing should decrease with increasing strain ad infinitum. Recently, two of us (T.B. and D.D.P.) have used a combination of numerical simulations and laboratory experiments to show that, with increasing applied stress, the normal stress acting between such fractures undergoes a transition from tensile to compressive, suggesting a cause for fracture saturation. Here we investigate the full stress distribution between such fractures, from which we derive an intuitive physical model of the process of fracture saturation. Such a model should find wide applicability, from geosciences to engineering.

Journal Article↗
PubMed1996

Space-time clustering of childhood leukaemia in Greece: evidence supporting a viral aetiology.

The method introduced by Knox for evaluation of space-time clustering has been applied to 872 cases of childhood (0-14 year old) leukaemia diagnosed in Greece over the 10 year period 1980-89. Greek towns are characterised by substantial population mixing due to internal migration, whereas there is relative isolation in mountainous rural areas. Predetermined space (5 km) and time (1 year) limits were used on the basis of previous reports in order to define the clustering cell. There is highly significant evidence for clustering of childhood leukaemia in Greece as a whole, the observed number of pairs that are close in both spaces and time exceeding the expected number by 5.2% (P = 0.004). The excess is particularly evident for leukaemia cases in 0 to 4-year-old children, among whom the observed number of pairs that are close in both space and time exceeded the expected number by 9.4% (P = 0.004). There is no evidence of space-time clustering for leukaemia cases older than 5 years. The overall pattern is descriptively similar in urban and semiurban areas and is especially marked for acute lymphoblastic leukaemia at the childhood peak ages (2-4 years) with an excess of 19% (P = 0.0006). In the rural population there is evidence for clustering of cases belonging to older and broader age groups, a phenomenon compatible with a delay in the development of herd immunity against putative infectious aetiological agents. The findings of the present study provide support for the hypothesis that a substantial proportion of cases of childhood leukaemia may arise as a rare sequel to exposure to an agent or agents, most probably viral in nature.

Adolescent↗
PubMed2003

Dodecahedral space topology as an explanation for weak wide-angle temperature correlations in the cosmic microwave background.

The current 'standard model' of cosmology posits an infinite flat universe forever expanding under the pressure of dark energy. First-year data from the Wilkinson Microwave Anisotropy Probe (WMAP) confirm this model to spectacular precision on all but the largest scales. Temperature correlations across the microwave sky match expectations on angular scales narrower than 60 degrees but, contrary to predictions, vanish on scales wider than 60 degrees. Several explanations have been proposed. One natural approach questions the underlying geometry of space--namely, its curvature and topology. In an infinite flat space, waves from the Big Bang would fill the universe on all length scales. The observed lack of temperature correlations on scales beyond 60 degrees means that the broadest waves are missing, perhaps because space itself is not big enough to support them. Here we present a simple geometrical model of a finite space--the Poincaré dodecahedral space--which accounts for WMAP's observations with no fine-tuning required. The predicted density is Omega(0) approximately 1.013 > 1, and the model also predicts temperature correlations in matching circles on the sky.

Journal Article↗
PubMed1997

Computed tomography in the diagnosis of buccal space masses.

OBJECTIVE: To evaluate the CT features of buccal space masses. PATIENTS AND METHODS: Fifty-three cases of buccal space masses were reviewed retrospectively. The diagnosis was confirmed histopathologically in all except two. CT images were assessed for the number, location, internal architecture and margin of the lesions and their relation to the surrounding structures. RESULTS: The series comprised 44 tumors (33 benign and 11 malignant) and nine non-tumorous lesions. Buccal gland tumors were all found adjacent to the outer surface of the buccinator, in contrast to epidermoid cysts and accessory parotid tumors which were completely separate from it. Hemangiomas were characterized by multiple masses or the presence of phleboliths. When ill-defined margins, violation of fascial planes and aggressive bone destruction were used as the criteria for the malignancy, only seven out of 11 malignant tumors were correctly diagnosed (sensitivity 64%). CONCLUSION: CT was useful in demonstrating the presence and location of the masses in the buccal space and sometimes in the differential diagnosis. For a mass of uncertain cause in the buccal space, a buccal gland tumor is the most likely diagnosis. The value of CT in differentiating malignant from benign buccal space lesions is limited.

Adolescent↗
PubMed1968

Changes of total water and sucrose space accompanying induced ion uptake or phosphate swelling of rat liver mitochondria.

1. Total water exchangeable with tritiated water and sucrose space were measured in rat liver mitochondria during the uptake of K(+) induced by valinomycin and the release caused by nigericin. The K(+) content and the sucrose-inaccessible water rose and fell together. 2. Swelling resulting from phosphate addition in a medium of high K(+) concentration was associated mainly with increased sucrose-accessible water, which carried dissolved K(+). This change was reversed by addition of ATP. 3. The response of the sucrose-inaccessible space to changed osmolarity was qualitatively that expected if the mitochondrial K(+) is assumed to be present in this space with a univalent anion. 4. It is brought out that the light-scattering method fails to distinguish between changes in sucrose space and in sucrose-inaccessible space, which in the present experiments could be altered respectively by phosphate (in high K(+) solution) and by cation uptake induced by antibiotic.

Acetates↗
PubMed2005

Redox activation of mitochondrial intermembrane space Cu,Zn-superoxide dismutase.

The localization of Cu,Zn-superoxide dismutase in the mitochondrial intermembrane space suggests a functional relationship with superoxide anion (O2*-) released into this compartment. The present study was aimed at examining the functionality of Cu,Zn-superoxide dismutase and elucidating the molecular basis for its activation in the intermembrane space. Intact rat liver mitochondria neither scavenged nor dismutated externally generated O2*-, unless the mitochondrial outer membrane was disrupted selectively by digitonin. The activation of the intermembrane space Cu,Zn-superoxide dismutase following the disruption of mitochondrial outer membrane was largely inhibited by bacitracin, an inhibitor of protein disulphide-isomerase. Thiol alkylating agents, such as N-methylmaleimide or iodoacetamide, decreased intermembrane space Cu,Zn-superoxide dismutase activation during, but not after, disruption of the outer membrane. This inhibitory effect was overcome by exposing mitochondria to low micromolar concentrations of H2O2 before disruption of the outer membrane in the presence of the alkylating agents. Moreover, H2O2 treatment alone enabled intact mitochondria to scavenge externally generated O2*-. These findings suggest that intermembrane space Cu,Zn-superoxide dismutase is inactive in intact mitochondria and that an oxidative modification of its critical thiol groups is necessary for its activation.

Animals↗
PubMed1985

Space anomalies, missing permanent teeth and orthodontic treatment.

Statistical association of crowding and spacing with age, sex, orthodontic treatment and extractions finds a tendency for more maxillary posterior spacing in males and more lower anterior spacing in females. Extractions were also associated with spacing. No association was found between spacing and orthodontic treatment.

Adult↗
PubMed2001

Immune surveillance of mouse brain perivascular spaces by blood-borne macrophages.

Virchow-Robin's perivascular spaces lie between the basement membrane around pericytes and the basement membrane at the surface of the glia limitans of the brain vessels. They are directly connected to the subpial space and harbour a population of cells distinct from pericytes, perivascular microglia and other cells within perivascular spaces (e.g. T cells and mast cells) in their ability to quickly phagocytose particles from the cerebrospinal fluid (CSF). Morphology, function, and cell surface proteins of these perivascular cells suggest an origin from the monocyte/macrophage lineage. It is currently unclear to what extent these brain perivascular cells represent a resident population of histiocytes or undergo continuous supplementation from blood monocytes. Using transplants of green-fluorescent-protein (GFP)-transfected bone marrow cells, we therefore investigated the replacement of perivascular cells by blood-borne macrophages in adult mice. GFP-positive cells in the perivascular spaces were found as early as 2 weeks post transplantation. The substitution of host perivascular cells by donor-derived macrophages was then evaluated using immunocytochemistry and intraventricular injection of hydrophilic rhodamine-fluorescent tracers. Such tracers diffuse along perivascular spaces and are subsequently phagocytosed by perivascular cells leading to stable phagocytosis-dependent labelling. Thus, the population of newly immigrated macrophages could be related to the total number of perivascular macrophages. This approach revealed a continuous increase of donor-derived perivascular cells. At 14 weeks post transplantation, all perivascular cells were donor-derived. These data show that brain perivascular cells are a population of migratory macrophages and not resident histiocytes.

Animals↗
PubMed2000

Comparative study of the temporomandibular joint space in maximum intercuspation and canine edge-to-edge positions in deep bite and non-deep bite subjects.

In order to study the relationship between morphological properties of the TMJ and the mathematically predicted force distribution in the TMJ, the geometric distribution of the joint space on top of the condylar surfaces was evaluated. Seven deep bite subjects and seven non-deep bite subjects were used, and the joint space in the maximum intercuspation and canine edge-to-edge positions was analysed in each group. Standardized images of the TMJ were taken with computed tomography (CT) using a mandible positioner. The comparative ratio of joint space (CRJS) between the maximum intercuspation and the canine edge-to-edge positions was calculated and summarized on the map of the mean morphological outline of the condyle. On the balancing-side condyle, the CRJS of small value was distributed mainly on the anterior edge of the condyle in the non-deep bite group, whereas, in the deep bite group, it was distributed on the centre of the condyle. On the working-side condyle, the small CRJS was distributed around the lateral pole of the condyle in the non-deep bite group, whereas, in the deep bite group, it was found around the posterior part of the condyle. The distribution pattern of CRJS on the upper surface of the condyle in the non-deep bite group was consistent with the results of previous studies on mathematical simulation of TMJ loading. From the results of this study, it was suggested that the distribution of mechanical loading on the TMJ in the eccentric mandibular position would be highly affected by the comparative ratio of joint space. As the comparative ratio of joint space would be highly affected by the condylar position, the analysis of the morphology of the TMJ in relation to mechanical joint loading, in a future investigation, should be carried out on specific mandibular positions in relation to the function of the TMJ to be studied.

Adult↗
PubMed1998

Optimization of genome search strategies for homozygosity mapping: influence of marker spacing on power and threshold criteria for identification of candidate regions.

Mapping of genes involved in rare recessive diseases is usually difficult because of the lack of families with more than one affected progeny. The problem may be avoided by using inbred affected individuals and the strategy of homozygosity mapping. In practice, the use of homozygosity mapping in a genome-wide scan requires that a set of markers regularly spaced and spanning the whole genome are tested. Investigators are then faced to the problem of choosing the spacing of markers. To help solve this problem, we give some useful clues by computing (1) the expected length of the region of identity by descent around the disease locus, (2) the distribution, given the spacing of markers, of the number of affected individuals expected not to be homozygous at the marker closest to the disease locus and, (3) the expected type-one error. We show that even if the markers are very closely spaced, it is not unlikely that some affected individuals in the sample will not be homozygous at the marker closest to the disease locus. Excluding a region by the criterion that all affected individuals in the sample are not homozygous may then dramatically increase the rate of false negatives. We thus propose to relax the criterion to declare a region candidate, based on the sample size and the spacing of markers.

Chromosome Mapping↗
PubMed1998

Analysis of interdigital spaces during mouse limb development at intervals following amniotic sac puncture.

A spectrum of limb abnormalities ranging from adactyly, syndactyly, acrosyndactyly to nail hypoplasia was encountered in mouse embryos subjected to amniotic sac puncture at the corresponding gestational stage when human chorionic villus sampling (cvs) would normally be performed clinically. Previous skeletal studies revealed that, apart from the occasional incidence of fusion of 2 distal phalanges, syndactyly usually only affected the soft tissues within the interdigital spaces. A similar situation was also observed in cases of adactyly; while the skeletal elements of the digits were present, the soft tissues in the interdigital spaces failed to separate. A transient period of bradycardia is induced, possibly secondary to compression of the embryo by the extraembryonic membranes and uterine muscles following amniotic sac puncture. These factors, we believe, produce temporary hypoxia/ischaemia of the distal extremities, and may lead to the modification of the interdigital mesenchymal tissues within the autopods. In order to investigate the mechanism(s) underlying soft tissue syndactyly, limbs recovered at 0.5, 4, 8, 12, 24, or 36 h following amniotic sac puncture (ASP) were examined histologically. Vascular disruption in the form of localised areas of haemorrhage, vascular dilatation and congestion and the presence of fluid-filled cavities occurred in relation to the marginal vein and vascular plexus in the interdigital spaces. It is hypothesised that this interfered with the normal equilibrium of the preset programs of mitosis/cell death and apoptosis within the mesenchymal cells of the interdigital spaces. Apoptosis in these areas was inhibited in the majority of the experimental limbs analysed 4 h after ASP. Instead of undergoing necrosis/apoptosis, increased mitotic activity was usually observed from 8 h following ASP at the sites where apoptosis would normally be expected to be seen. The aberrant fate of the interdigital mesenchyme following ASP and the underlying mechanism(s) involved are discussed, as is the critical importance of an adequate vascular supply to the interdigital spaces during the morphogenesis of the autopod. We believe that this report contributes to understanding the mechanism(s) which lead to syndactyly following ASP, and the limb defects occasionally seen following cvs when this is undertaken during early gestation.

Animals↗
PubMed1996

Dilated intercellular spaces: a morphological feature of acid reflux--damaged human esophageal epithelium.

BACKGROUND & AIMS: Dilated intercellular spaces are a sign of epithelial damage in acid-perfused rabbit esophagus, a change best identified by transmission electron microscopy. The aim of this study was to determine if this change is also a feature of acid damage to human esophageal epithelium. METHODS: Endoscopic esophageal biopsy specimens from patients with (n = 11) and without (n = 13) recurrent heartburn were examined using transmission electron microscopy. Of 11 patients with heartburn, 6 had erosive esophagitis and 5 had normal-appearing mucosa on endoscopy; 13 controls had no symptoms or signs of esophageal disease. Using a computer, intercellular space diameter was measured from transmission electron microscopy photomicrographs of the specimen from each patient. RESULTS: Intercellular space diameter was significantly greater in specimens from patients with heartburn than those from controls; this was true irrespective of whether the patient had erosive or nonerosive disease. Space diameters of > or = 2.4 microns were present in 8 of 11 patients with heartburn and in no controls. CONCLUSIONS: Dilated intercellular spaces are a feature of reflux damage to human esophageal epithelium. As a morphological marker of increased paracellular permeability, its presence in patients without endoscopic abnormalities may help explain their development of heartburn.

Adult↗
PubMedDate not supplied

Effect of disk fenestration on sagittal kinematics of the canine C5-C6 intervertebral space.

OBJECTIVE: To determine the effect that ventral intervertebral disk fenestration has on the sagittal range of motion about the C5-C6 intervertebral space. STUDY DESIGN: A repeated measures in vitro mechanical study of spinal range of motion under controlled loading conditions before and after fenestration. SAMPLE POPULATION: A total of 10 canine cervical vertebral specimens (C4-C7) collected from clinically normal animals within 12 hours of euthanasia. METHODS: Specimens were loaded as cantilever beams fixed at C7. Weights (1 to 5 kg) were progressively applied to C4 to produce flexion or extension in the sagittal plane. Radiographs were taken at each load, 3 times before and 3 times after fenestration of the C5-C6 disk. The positions of radiodense markers embedded in the vertebrae were used to calculate flexion and extension angles and range of motion. RESULTS: Range of motion (difference between flexion and extension) and flexion and extension angles (individually) significantly increased after fenestration (P < .0001). CONCLUSION: Ventral fenestration produces sagittal instability of the C5-C6 disk space. CLINICAL RELEVANCE: In surgical fusion of caudal cervical intervertebral spaces in dogs, radiographically normal disks adjacent to the affected space are often fenestrated to facilitate distraction before surgical stabilization. This study shows that ventral fenestration produces instability of a caudal cervical intervertebral space in the model used. Such instability may contribute to the development of the secondary instability ("domino lesions") seen in some surgically treated dogs.

Animals↗
PubMed2003

[Oropharyngeal vocal tract space during singing--comparison of tactile-kinesthetic and auditory perception with objective endoscopic findings].

BACKGROUND: In this study we compared the perceived diameter of the vocal tract's oropharyngeal part with the diameter that was determined endoscopically. METHODS: 28 singers (13 male, 15 female) were examined with transnasal fiberscopic pharyngoscopy while singing the vowels /a/, /i/ and /u/ in 4 different timbres (normal, opened, covered, dumpled) and 3 different pitches (chest/modal register, subjective comfortable pitch for singing, head/falsetto register). The tactile-kinesthetic and auditive rating of the singers, the auditive rating of a singing teacher and the visual-endoscopic analysis of three laryngologists were compared. RESULTS: The tactile-kinesthetic and auditory self-perception of the singers was quite different from the auditive perception of a singing teacher and visual endoscopic findings of the laryngologists. The singers had the impression that the different singing timbres (normal, opened, covered, dumpled) influence oropharyngeal vocal tract space during singing. They judged the vowel itself and the pitch as having very little influence. Based on his auditory perception, the singing teacher also rated that the timbre plays an important role for the oropharyngeal vocal tract space but he found vowels to be the parameter with the greatest impact. Via visual endoscopic examination we found that, among the three parameters (vowel, timbre, pitch), the different vowels are most influential on the oropharyngeal vocal tract space. Analysis of video sequences revealed that pitch and timbre are less important. CONCLUSION: Subjective tactile-kinesthetic and auditory perception of the singers differs from auditory perception of the singing teacher as well as from endoscopic findings. The endoscopically determined oropharyngeal vocal tract space during singing the vowels /i/ or /u/ tends to be larger compared to the oropharyngeal vocal tract space while singing the vowel /a/.

Adult↗
PubMed1985

Changes in the respiratory gas tensions of a pneumonectomy space and their application to the diagnosis of bronchopleural fistula.

The oxygen (pO2) and carbon dioxide (pCO2) gas tensions of a pneumonectomy space were studied in an animal model. The 2 gases were measured in a standard blood gas analyser. The space gas pO2 and pCO2 equilibrated to a steady state within 48 hours of thoracotomy (pO2 mean 53.9 +/- 9.3 SD torr; pCO2 mean 44.8 +/- 9.9 SD torr). In the presence of a bronchopleural fistula (BPF), the pO2 rose significantly (mean pO2 118.4 +/- 13.2 SD torr; p less than 0.001). The space pCO2 usually fell, but the response was inconsistent (mean pCO2 33.6 +/- 16.4 SD; p = NS). A further rise in space pO2 could sometimes be induced by allowing the animals to breathe 100% oxygen by face mask. Data from 4 clinical cases of BPF support the concept that measurement f the space gas pO2 could be used as a bedside test for BPF.

Animals↗
PubMed2003

Space-time complexity in Hamiltonian dynamics.

New notions of the complexity function C(epsilon;t,s) and entropy function S(epsilon;t,s) are introduced to describe systems with nonzero or zero Lyapunov exponents or systems that exhibit strong intermittent behavior with "flights," trappings, weak mixing, etc. The important part of the new notions is the first appearance of epsilon-separation of initially close trajectories. The complexity function is similar to the propagator p(t(0),x(0);t,x) with a replacement of x by the natural lengths s of trajectories, and its introduction does not assume of the space-time independence in the process of evolution of the system. A special stress is done on the choice of variables and the replacement t-->eta=ln t, s-->xi=ln s makes it possible to consider time-algebraic and space-algebraic complexity and some mixed cases. It is shown that for typical cases the entropy function S(epsilon;xi,eta) possesses invariants (alpha,beta) that describe the fractal dimensions of the space-time structures of trajectories. The invariants (alpha,beta) can be linked to the transport properties of the system, from one side, and to the Riemann invariants for simple waves, from the other side. This analog provides a new meaning for the transport exponent mu that can be considered as the speed of a Riemann wave in the log-phase space of the log-space-time variables. Some other applications of new notions are considered and numerical examples are presented.

Journal Article↗