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PubMed2001

Enhanced intestinal motility influences absorption in anaesthetized rat.

The subject of this investigation was to study influence of the intestinal motility on absorption of 3-o-methyl-D-glucose (3-OMG), mannitol and polyethylene glycol (PEG 4000), used as absorption route markers, while monitoring cardiovascular parameters in an intestinal in situ model in rats. Rats were anaesthetized with Inactin(R) and Rapinovet(R). A segment of duodenum, approximately 10 cm, was perfused single-pass with saline containing unlabelled and radioactive 3-OMG, PEG 4000 or mannitol. The PEG 4000 was recovered almost completely in the intestinal perfusate suggesting an intact mucosal integrity. Most animals exhibited an intestinal contractile activity resembling fed motility except seven out of 19 given Rapinovet, which showed a 'burst-type' pattern resembling migrating motor complex (MMC). Absorption of 3-OMG in rats with MMC-like motility appears to be lower than in rats with fed-like motility, while no such difference was seen for mannitol. Moreover, there was a positive correlation (r 2=0.75) between intestinal activity (fed) and absorption of 3-OMG, but not with absorption of mannitol. The carrier-mediated absorption of 3-OMG was not only influenced by intestinal motility, but also by its pattern. This was not observed with mannitol, which is passively absorbed.

3-O-Methylglucose↗
PubMed2003

Exploring heart lymphatics in local drug delivery.

BACKGROUND: Local intramyocardial delivery (IMD) is under active clinical investigation for cell therapies to treat congestive heart failure, and gene therapies to induce revascularization of ischemic myocardium in coronary artery disease. Locally delivered agents can migrate away from the site of delivery through pathways that include lymphatics. Postdelivery redistribution can be observed using fluorescent tracers of different physical geometries. This approach provides a means to characterize these pathways and to delineate their importance in local cardiovascular drug delivery. METHODS AND RESULTS: The left ventricular wall of rats (N = 83) received injections of fluorescent microspheres with mean diameters ranging from 20 nm to 15,000 nm. Fluorescent microscopy was used to observe and image the patterns of migration from the epicardial surface. The animals were sacrificed after delivery. The microspheres with diameters smaller than 200 nm were widely distributed within the lymphatic network on the epicardial surface of the rat heart and through the ventricular wall at the injection site. Cardiac lymph nodes were identified with 20 nm and 100 nm deliveries, but could not be identified in any deliveries 200 nm or larger. The 15000 nm microspheres did not migrate. CONCLUSIONS: Tortuous lymphatic pathways are apparent in the images of fluorescent sphere migration from the intramyocardial site of delivery. These images suggest a lymphatic role in the formation of native collaterals that may implicate potential advantages to IMD in therapeutic angiogenesis. Distribution postdelivery also suggests that IMD may provide a means to administer hydrophilic agents to the periadventitial zone of the arterial wall to limit restenosis. The lack of redistribution of the 15,000 nm microspheres supports the potential for cell therapies to remain localized over an extended time frame.

Animals↗
PubMed2005

EBRA-FCA for measurement of migration of the femoral component in surface arthroplasty of the hip.

Studies on the migration of an implant may be the only way of monitoring the early performance of metal-on-metal prostheses. The Ein Bild Roentgen Analyse--femoral component analysis (EBRA-FCA) method was adapted to measure migration of the femoral component in a metal-on-metal surface arthroplasty of the hip using standard antero-posterior radiographs. In order to determine the accuracy and precision of this method a prosthesis was implanted into cadaver bones. Eleven series of radiographs were used to perform a zero-migration study. After adjustment of the femoral component to simulate migration of 3 mm the radiographs were repeated. All were measured independently by three different observers. The accuracy of the method was found to be +/- 1.6 mm for the x-direction and +/- 2 mm for the y-direction (95% percentile). The method was validated using 28 hips with a minimum follow-up of 3.5 years after arthroplasty. Seventeen were sound, but 11 had failed because of loosening of the femoral component. The normal (control) group had a different pattern of migration compared with that of the loose group. At 29.2 months, the control group showed a mean migration of 1.62 mm and 1.05 mm compared with 4.39 mm and 4.05 mm in the failed group, for the centre of the head and the tip of the stem, respectively (p = 0.001). In the failed group, the mean time to migration greater than 2 mm was earlier than the onset of clinical symptoms or radiological evidence of failure, 19.1 versus 32.2 months (p = 0.001) and 24.8 months (p = 0.012), respectively. EBRA-FCA is a reliable and valid tool for measuring migration of the femoral component after surface arthroplasty and can be used to predict early failure of the implant. It may be of value in determining the long-term performance of surface arthroplasty.

Adult↗
PubMed1979

Required neural involvement in control of canine migrating motor complex.

This study evaluated the effects of muscarinic, nicotinic, and adrenergic neuronal blockade on the migrating motor complex (MMC) in four unanesthetized dogs. Circular muscle contractile activity was recorded from eight strain gauge force transducers implanted on the stomach and small intestine of each dog. Both atropine sulfate and hexamethonium bromide significantly increased the period of the MMC. When the complex returned after hexamethonium administration, the period of the succeeding complexes was significantly decreased when compared to control. Guanethidine sulfate significantly increased contractile activity on the pylorus, duodenum, and jejunum with a corresponding disruption of the MMC pattern. The migrating motor complex requires the preganglionic release of acteylcholine and possibly an inhibitory input from the sympathetic nervous system for its normal appearance.

Animals↗
PubMed2003

Long-term results with the BiCONTACT system--aspects to investigate and to learn from.

The BiCONTACT femoral stem for cementless fixation is being used without any technical modification after 15 years. The long-term results should be evaluated in this study. A consecutive series was continuously monitored in a prospective follow-up study. A survival analysis was performed, clinical results were rated according to the Harris score. There were 236 patients with 250 total hip replacements (THR); mean age at time of implantation was 58.2 years. Indications for THR included osteoarthritis (62.4%), dysplasia (16.8%), trauma (8.4%) and femoral-head necrosis (16.8%). Average time of follow-up evaluation was 8.9 years (range 7.4-10.7 years). At follow-up, 27 patients had died and two could not be located. Seven patients were revised--two for infection, one for recurrent dislocation, two for component undersizing with rapid subsidence, and one for aseptic loosening of a varus-malaligned stem; one radiologically well-fixed stem had been revised during acetabular revision. Survival estimate showed an overall survival rate of 97.1% after 11 years (confidence limits: 98.7% upper and 93.6% lower). Radiologically, tiny reactive lines (< 2 mm) were present in the distal zones of the femoral shaft, but no radiolucencies could be found in the proximal anchoring zone. Migration analysis with Ein-Bild-Röntgen-analyse/femoral component analysis (EBRA/FCA) demonstrated a very small amount of migration: in 31.0%, the overall migration was between 0.5 and 1 mm after 120 months; 8.5% had an absolute amount of subsidence exceeding 2 mm after 120 months (one case more than 3 mm). Mean subsidence was 0.2 mm after 3 months and 6 months, 0.3 mm after 12 months, and reached 0.5 mm after 10 years. An initial small amount of subsidence could be detected in 45.1%, and 15.5% had a late onset of subsidence. Continuous sinking could be found in 12.7%, while 26.8% had irregular patterns of migration. Clinical results were somewhat compromised by a higher-than-average rate of cup loosening (uncoated threaded cup). The average Harris hip score at follow-up was 84.3 points. Interestingly, no femoral osteolysis could be detected, even in cases with severe acetabular osteolyses, indicating sealing of the stem interface by tight osseointegration of the proximally-coated stem.

Arthroplasty, Replacement, Hip↗
PubMed1999

Colonisation of the developing human brain and spinal cord by microglia: a review.

Microglia are the immune effector cells of the nervous system. The prevailing view is that microglia are derived from circulating precursors in the blood, which originate from the bone-marrow. Colonisation of the central nervous system (CNS) by microglia is an orchestrated response during human fetal development related to the maturation of the nervous system. It coincides with vascularisation, formation of radial glia, neuronal migration and myelination primarily in the 4th-5th months and beyond. Microglial influx generally conforms to a route following white matter tracts to gray areas. We have observed that colonisation of the spinal cord begins around 9 weeks, with the major influx and distribution of microglia commencing around 16 weeks. In the cerebrum, colonisation is in progress during the second trimester, and ramified microglial forms are widely distributed within the intermediate zone by the first half of intra-uterine life (20-22 weeks). A distinct pattern of migration occurs along radial glia, white matter tracts and vasculature. The distribution of these cells is likely to be co-ordinated by spatially and temporally regulated, anatomical expression of chemokines including RANTES and MCP-1 in the cortex; by ICAM-2 and PECAM on radiating cerebral vessels and on capillaries within the germinal layer, and apoptotic cell death overlying this region. The phenotype and functional characteristics of fetal microglia are also outlined in this review. The need for specific cellular interactions and targeting is greater within the central nervous system than in other tissues. In this respect, microglia may additionally contribute towards CNS histogenesis.

Brain↗
PubMed1986

Loosening of the cemented hip prosthesis. The importance of heat injury.

The cemented hip arthroplasty is one of the most successful orthopedic operations. However, the results do deteriorate with time because of mechanical loosening. Some hips with obviously loose prosthetic components are not painful. This discrepancy between symptoms and radiographic evidence of loosening has caused uncertainty about the diagnostic criteria that should be applied. This uncertainty has in turn led to confusion about the basic cause of loosening. The aims of this presentation were to find a favorable definition of loosening and to investigate the etiology of mechanical loosening of the cemented hip prosthesis. The diagnostic criteria of contrast and radionuclide arthrography, bone scintigraphy, and roentgen stereophotogrammetric analysis (RSA) were evaluated in 14 symptomatic hip arthroplasties examined by these methods. Loosening was found to be best defined as migration; regardless of diagnostic criterion, all loose prosthetic components were migrating, but no nonmigrating component was loose. The development of the radiolucent zone was analyzed in a simple model consisting of 6 cases of giant-cell tumor of bone successfully treated by curettage and cementing. In locations where the cement filling adjacent to cancellous bone was concave, a considerably wider zone developed. There was a positive correlation between the width of the zone and the volume of cement. The radiolucent zone in this model could be explained by heat injury during the polymerization of bone cement. The pattern of migration of the components in 20 cemented hip prostheses was studied with RSA and with conventional radiography over a period of 2 years postoperatively. Eleven acetabular and three femoral components migrated. After an initial 4-month period of rapid migration, most components migrated slowly. The initial rapid migration could be accounted for by the resorption of a layer of necrotic bone following heat injury during the polymerization. The less frequent migration of the metallic femoral component as compared with the polyethylene acetabular component could be explained by the metal acting as a heat sink. Radiographic examination was found to be unsatisfactory as a means of detecting mechanical loosening during the first 2 postoperative years. RSA, on the other hand, was capable of revealing migration as early as 4 months postoperatively. Migration of the components in 16 hip prostheses was studied with RSA for 1 year postoperatively following randomized use of low- and high-viscosity cement. As regards prosthetic migration, no difference was detected between the two types of cement; low-viscosity cement did not improve prosthetic fixation.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetabulum↗
PubMed1982

The purification and characterization of multiple forms of mouse submaxillary gland renin.

Five forms of renin, A0, A, C, D and E, from mouse submaxillary gland were purified by a two-step procedure including chromatography on the immunoaffinity column and CM-cellulose column. Four renin fractions, A0, A, C and E were purified to homogeneity by the criteria of polyacrylamide gel electrophoresis, analytical isoelectric focusing and Ouchterlony double immunodiffusion. All these forms of renin have molecular weights of 40 000 as determined by gel filtration on Sephadex G-100 column. No high molecular weight renin could be demonstrated. Individual renin fractions showed similar angiotensin I formation activity, 52-158 ng angiotensin I/ng protein per h. No other protease activity could be detected with hemoglobin or casein as substrate. These purified proteins showed a discrete pattern of migration under polyacrylamide gel electrophoresis. Under denaturing condition in SDS-gel electrophoresis, all but fraction D showed a protein band with a molecular weight of 30 000. Fraction D showed a major component with molecular weight of 33 000. The isoelectric points of these renin forms varied from 5.46 to 5.76. They all reacted with antibody raised against renin A and showed similar pressor response activity with 20 ng quantities of the purified proteins. The closely related characteristics of these five forms of renin were further demonstrated by their similarity in peptide mapping patterns after limited digestion with Staphylococcus aureus V8 protease. The data suggest that these proteins are homologous proteins.

Animals↗
PubMed2005

Population genetic structure of a nonmigratory estuarine fish (Fundulus heteroclitus) across a strong gradient of polychlorinated biphenyl contamination.

Populations of the estuarine fish Fundulus heteroclitus indigenous to contaminated sites exhibit heritable resistance to some of the toxic effects of early life-stage exposure to polychlorinated biphenyls (PCBs). This evolved tolerance provides evidence of strong selection by PCBs, and it suggests other potential genetic effects of these stressors on resident populations. Environmental contaminants have the potential to affect the genetic structure of populations and to reduce genetic diversity, but species life-history traits, particularly patterns of migration and dispersal, also influence the distribution of genetic variation among populations. Therefore, the present was conducted to determine whether genetic diversity or genetic structure is altered in populations of F. heteroclitus indigenous to 18 sites in Massachusetts (USA) and Rhode Island (USA), representing a steep gradient of sediment PCB contamination and culminating in a Superfund site at New Bedford Harbor (NBH; MA, USA). Allele frequencies at enzymatic loci were used to assess genetic structure and diversity. Selection experiments using a highly toxic PCB congener (3,3',4,4',5-pentachlorobiphenyl) were conducted to determine if genetic patterns at field sites could be associated with contaminant exposures. Although allele frequencies clearly reflected a pattern of isolation by distance, the results indicated neither significant loss of genetic diversity nor alteration of allele frequencies for populations of F. heteroclitus in NBH.

Adaptation, Physiological↗
PubMed1989

A circadian rhythm of population behavior in Gonyaulax polyedra.

Like other flagellates, Gonyaulax polyedra exhibits diurnal vertical migration and pattern formation. Shape and size of the aggregations depend on container type, light intensity, and cell density. In Petri dishes, cells form oval "swarms"; within these, cells move downward in the highly dense center and rise up at the periphery. We have investigated the daily rhythm of this swarming activity in Petri dishes illuminated from the side, using time-lapse video recordings. At night, a "lawn" of cells forms at the bottom of the dish toward the light source (independent of light intensity). Before dawn, cells rise toward the surface and aggregate in swarms. The daily vertical migration occurs independent of light direction and intensity. The diurnal swarms, however, form every day at the same location within the dish, at a distance from the light that depends on light intensity, indicating a self-selection of light intensity. In constant light and temperature and with negligible vertical nutrient differences, all aspects of the rhythm continue to oscillate for up to 3 weeks, when the rhythm of the population becomes desynchronized. Under cycles of bright white-dim red light (WR), cell entrain to WR 10:10 but free run in WR 8:8 and shorter cycles, showing relative coordination (von Holst, 1939) to the driving light cycle. They also entrain to the 24-hr multiple of WR 6:6. Under nonentrained conditions, swarming activity is still influenced by light changes, and in spite of the apparent free run, the phasing of the averaged activity varies systematically with different T-cycle frequencies.

Animals↗
PubMed1994

Correlation between esterase electrophoretic polymorphism and virulence-associated traits in extra-intestinal invasive strains of Escherichia coli.

The electrophoretic variations of carboxylesterase B and of esterases A, C and I, the presence of mannose resistant haemagglutinin, alpha-haemolysin, cytotoxic necrotizing factor type 1 (CNF1) and certain O antigens were compared in 150 strains of Escherichia coli responsible for extra-intestinal infections. Electrophoretic mobilities of outer membrane proteins (OMP) were also studied for strains belonging to O4, O6, O7, O8 and O75 serogroups. Fast migrating allozymes of carboxylesterase B (pattern B1) were correlated with slow migrating allozymes of esterase C, serogroups O7 and O8, lack of virulence factor, and particular OMP patterns, whereas slow migrating allozymes of carboxylesterase B (pattern B2) were correlated with fast migrating allozymes of esterase C, serogroups O2, O4, O6, O18 and O75, virulence factor production, and distinct OMP patterns. Allozymes of esterases A and I were not clearly correlated with the distribution of virulence factors. The pattern B2 was more strongly associated with CNF1 than with alpha-haemolysin and mannose resistant haemagglutinin. These results substantiate the view that the electrophoretic pattern B2 of carboxylesterase B identified most of the highly pathogenic strains implicated in extra-intestinal infection of humans.

Bacteremia↗
PubMed1996

Migration of press-fit cups fixed with poly-L-lactic acid or titanium screws: a randomized study using radiostereometry.

The early migration of porous acetabular cups was studied in 43 patients with osteoarthrosis. The patients were randomly allocated to additional fixation of the cup with either biodegradable poly-L-lactic acid screws or titanium screws. Radiostereometric evaluation was done during the first 2 years after the procedure in 43 hips (23 with poly-L-lactic acid screws and 20 with titanium screws). At the 2-year follow-up, cups fixed with poly-L-lactic acid screws had migrated significantly more in the proximal-distal (p < 0.05) and medial-lateral (p < 0.05) directions. Cups with titanium screws displayed more pronounced rotations around the longitudinal axis (p < 0.05). Postoperatively, on the lateral view, there was an increased occurrence of radiolucencies at the dome of the cups fixed with poly-L-lactic acid screws (p < 0.05). The clinical result did not differ between the two groups. Inferior implant-bone contact in the poly-L-lactic acid group, local changes of the bone quality, and diminishing support of the poly-L-lactic acid screws caused by their degradation with time could be reasons for the different pattern of migration observed.

Acetabulum↗
PubMed1991

The role of NK cells in the regulation of experimental metastasis in a murine lymphoma system.

This report describes the role of natural killer (NK) cells in regulating the localization of two closely related murine lymphomas (ASL1 and ASL1w) to various organ sites. These tumors are phenotypically similar yet differ in their overall malignancy and experimental metastatic pattern. Both tumors show similar patterns of migration in kinetic studies, however, they vary in their NK susceptibility. Cold target inhibition analysis and assessment of susceptibility to cytotoxic T lymphocytes (CTL) suggested that the NK resistance of ASL1 was due to the lack of expression of a relevant target structure(s) required for NK recognition. The role of NK cells in regulating the growth of the tumors in vivo was studied by altering NK cell levels in recipient mice prior to tumor injection. Neither NK cell depletion nor augmentation affected the growth of the NK resistant ASL1 tumor but NK depletion significantly shortened the mean survival time (MST) of recipients of the NK sensitive ASL1w tumor as well as changed its metastatic pattern; conversely, NK augmentation significantly increased the MST of ASL1w recipients. These data suggest that NK cells play a critical role in determining the metastatic characteristics of the ASL1w lymphoma.

Animals↗
PubMed1989

Proximal trajectory of the brachium conjunctivum in rat fetuses and its early association with the parabrachial nucleus. A study combining in vitro HRP anterograde axonal tracing and immunocytochemistry.

The proximal course of the developing brachium conjunctivum (BC) in the rat described from embryonic day 16 (E16) to one day postnatal (P1). Axons of the cerebellar deep nuclear neurons entering this bundle were identified by anterograde axonal tracing after in vitro horseradish peroxidase (HRP) injections in the cerebellar plate. At all ages, the main ascending limb of the BC can be followed from its emergence, dorsal to the cerebellar plate where it assumes an almost vertical course, up to its decussation. Close to the ventricle at E16, the decussating fibers are progressively displaced ventrally probably because of the fusion, on the midline, of bilaterally produced raphe neurons. In E16 and E17 embryos, labeled BC fibers extend beyond the decussation in the caudal part of the red nucleus. Decussating BC axons, in some E16 early embryos, end with large and complicated growth cones, as described previously in 'decision regions' for chick embryo motoneurons. Growth cones were never observed in this region in older embryos. In addition to the main ascending limb of the BC, we also traced its ipsilateral descending limb and the cerebello-olivary projections. In parallel, the development of a nucleus immunoreactive for the vitamin D-dependent calcium-binding protein (CaBP) is reported. By E16, its neurons migrate rostrally and settle in the region where the BC is demonstrated by tracing experiments. At E17 and thereafter this isthmic nucleus is composed of a shell of CaBP-immunoreactive neurons ensheathing an immunonegative cylinder. Between E17 and birth, in spite of the profound modifications of the isthmic region, this CaBP-immunoreactive nucleus remains in close proximity to the BC. This nucleus is identified as the marginal nucleus of the BC or parabrachial nucleus, by double-labeling experiments combining the visualization of the retrogradely labeled axons and neurons of the deep cerebellar nuclei inside the CaBP immunofluorescently labeled parabrachial nucleus. Subsequently the deep cerebellar neurons translocate caudoventrally moving away from the parabrachial nucleus inside which their axons become visible. This pattern of migration could indicate that a few neurons of the deep nuclei remain ectopic, wedged between the restiform body and the BC while receiving an appropriate Purkinje cell (PC) projection.

Animals↗
PubMed1996

Zebrafish pigmentation mutations and the processes of neural crest development.

Neural crest development involves cell-fate specification, proliferation, patterned cell migration, survival and differentiation. Zebrafish neural crest derivatives include three distinct chromatophores, which are well-suited to genetic analysis of their development. As part of a large-scale mutagenesis screen for embryonic/early larval mutations, we have isolated 285 mutations affecting all aspects of zebrafish larval pigmentation. By complementation analysis, we define 94 genes. We show here that comparison of their phenotypes permits classification of these mutations according to the types of defects they cause, and these suggest which process of neural crest development is probably affected. Mutations in eight genes affect the number of chromatophores: these include strong candidates for genes necessary for the processes of pigment cell specification and proliferation. Mutations in five genes remove part of the wild-type pigment pattern, and suggest a role in larval pigment pattern formation. Mutations in five genes show ectopic chromatophores in distinct sites, and may have implications for chromatophore patterning and proliferation. 76 genes affect pigment or morphology of one or more chromatophore types: these mutations include strong candidates for genes important in various aspects of chromatophore differentiation and survival. In combination with the embryological advantages of zebrafish, these mutations should permit cellular and molecular dissection of many aspects of neural crest development.

Adaptation, Physiological↗
PubMed2006

Visualization and characterization of inflammatory cell recruitment and migration through the corneal stroma in endotoxin-induced keratitis.

PURPOSE: The infiltration of inflammatory cells into the cornea is a major determinant in the outcome of keratitis. The purpose of this study was to use enhanced green fluorescence protein (EGFP) bone marrow chimeric mice to visualize and characterize the inflammatory cells that migrate to the corneal stroma during endotoxin-induced keratitis and to explore the mechanisms underlying this process. METHODS: Keratitis was induced by injecting endotoxin into the corneas of EGFP chimeric mice. In vivo fluorescence stereomicroscopy was used to visualize in real time the recruitment of EGFP-positive cells at different time points. Immunohistochemistry and three-dimensional (3D) confocal analysis of whole-mount corneas was used for histologic characterization. Macrophage inflammatory protein-2 (MIP-2) chemokine was neutralized in vivo to determine its contribution to this process. RESULTS: Recruitment of EGFP-positive inflammatory cells in the corneal stroma can be detected in vivo by 6 hours after the injection of endotoxin, and these were mainly neutrophils. Full-thickness whole corneal mount confocal image analysis showed a distinct pattern of migration of EGFP inflammatory cells through the anterior corneal stroma. Moreover, inflammatory cells did not colocalize with the injected lipopolysaccharide (LPS) deposits in the stroma but moved from all directions toward LPS, partially in response to the production of the chemokine MIP-2. CONCLUSIONS: EGFP chimeric mice and ex vivo 3D analysis of whole-mount corneas provides unique information on the interaction of infiltrating inflammatory cells in the cornea. These findings demonstrate that a chemotactic gradient triggered in part by MIP-2 is responsible for directing inflammatory cell migration through the corneal stroma.

Animals↗