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Apposition
Kinds of Apposition Terms modified by Apposition Selected AbstractsMesothelioma Symposium 11.30,12.30 Tuesday 16 September 2003CYTOPATHOLOGY, Issue 2003Darrel Whitaker Dr The diagnosis of malignant mesothelioma on the cytology of serous effusions is a two-phase process. First is to determine that the effusion is malignant based on morphological features such as a highly cellular fluid with many large three dimensional cell aggregates, and/or the recognition of minor malignant criteria including prominent cell engulfment, uniformly present very prominent nucleoli, or the finding of very large (giant) cells. In cell block sections, strong positive staining with EMA often with cell membrane accentuation provides compelling support for a cytological diagnosis of malignancy. Second is to recognize that the malignant cells have a mesothelial phenotype and do not represent metastatic malignancy (usually adenocarcinoma). Criteria in support of mesothelioma include the lack of a ,two cell' population, that is one native (mesothelial) and one foreign (metastatic), cells with abundant dense staining cytoplasm, the presence of ,windows' where mesothelioma cells lie in close apposition and intracytoplasmic glycogen presenting either as small peripheral vacuoles on MGG stained smears or large yellow refractile crescents on Papanicolaou stained smears. In addition, mesothliomas often possess connective tissue stromal cores occurring as either well-formed collagen within papillary aggregates or lying free as pink (MGG) or light green (Pap) amorphous material in the background of the smear or in loose association with mesothelioma cells. Finally small orange staining squamous-like cells can occasionally be identified and sometimes this may be a very prominent finding and has resulted in the false impression of a squamous cell carcinoma. Almost certainly these cells represent apoptotic tumour cells. The connective tissue mucin hyaluronic acid may be found as a net-like pattern in the smear background or as large hard-edged magenta-stained vacuoles on MGG-stained smears. Cell block sections provide architectural information and it is usually possible to separate mesothelioma aggregates with their cuboidal cells, central nuclei and abundant dense cytoplasm arranged in solid, papillary or hollow clusters from those of adenocarcinoma with less dense, often foamy cytoplasm, often composed of columnar cells with elongated nuclei. Aggregate form in adenocarcinoma can be variable but true acini are a rare finding. These cell block sections provide an ideal medium for histochemistry (PAS with and without diastase digestion) and immunocytochemistry. By using a panel of antibodies (Calretinin and CK 5/6, BerEp4, CEA, B72.3) it is almost always possible to distinguish mesothelioma from metastatic adenocarcinoma. Calretinin and CK 5/6 positive staining and absent staining with BerEp4, CEA and B72.3 is considered diagnostic of mesothelioma. [source] Use of Intraoperative Botulinum Toxin in Facial ReconstructionDERMATOLOGIC SURGERY, Issue 2 2009TIMOTHY CORCORAN FLYNN MD BACKGROUND Botulinum toxin is a potent neuromodulator that temporarily relaxes muscles and can improve wound healing. OBJECTIVE This retrospective analysis assessed the use of intraoperative botulinum toxin type A or B in patients undergoing surgical reconstruction after Mohs micrographic surgery for treatment of skin cancer. The primary effect of intradermal botulinum toxin on wound healing was also studied. METHODS & MATERIALS Charts of patients who received intraoperative botulinum toxin type A (n=9) or B (n=9) in conjunction with reconstructive surgery after Mohs micrographic surgery were reviewed. Three volunteers also underwent dermal injections of botulinum toxin type A followed by erbium laser resurfacing. RESULTS Outcomes did not differ in patients treated with botulinum toxin type A and type B. Patients had excellent apposition of wound edges and smooth skin overlying soft tissue; no significant complications were noted. Healing of erbium laser ablation did not differ between botulinum toxin type A,treated skin and control skin. CONCLUSIONS Administration of botulinum toxin type A or B after reconstruction after Mohs micrographic surgery aided wound healing; botulinum toxin type A and botulinum toxin type B were equally effective. Intradermal botulinum toxin type A demonstrated no primary effect on healing of erbium laser,resurfaced skin. [source] Microscopic structure of the sperm storage tubules in the polygynandrous alpine accentor, Prunella collaris (Aves)ACTA ZOOLOGICA, Issue 4 2001Akira Chiba Abstract We describe the microscopic structure of the sperm storage tubules (SSTs) of the polygynandrous alpine accentor, Prunella collaris. The SSTs were found at the utero-vaginal junction of the oviduct and were composed of a single layer of columnar epithelium. The cells of the tubule proper were non-ciliated and had a round or oval nucleus in their basal portion. Their cytoplasm was finely or coarsely vacuolated due to lipid inclusions. Under the electron microscope, the epithelial cells exhibited a number of mitochondria, Golgi bodies, occasional lysosome-like dense bodies, granular endoplasmic reticula, junctional complex, and tonofilaments. The apical margin of the cells was fringed with numerous microvilli. The epithelial lining of the SSTs was devoid of mucous cells, but showed occasional infiltration of lymphoid cells. No contractile elements were found in association with the SSTs, but a close apposition of unmyelinated nerve fibres to the basal part of the SST cells was recognized. Intraluminal sperm were arranged in bundles, and their heads were orientated towards the distal portion of the SSTs. Evidence for engulfment of sperm by the SST cells was obtained for the first time. A sign of atrophy or regression of the SSTs was found in one specimen. [source] Reference Values Describing the Normal Mitral Valve and the Position of the Papillary MusclesECHOCARDIOGRAPHY, Issue 7 2007Petrus Nordblom M.Sc. In patients with functional mitral regurgitation (MR), the principal mechanisms are insufficient coaptation due to dilatation of the mitral annulus (MA), global ventricular dysfunction with tethering of leaflets, or restricted leaflet motion with incorrect apposition due to regional ventricular dysfunction and displacement of the papillary muscles (PMs). These different entities often coexist and for this reason, knowledge of the normal reference values describing the shape and size of the MA and the position of the PMs is essential. In the present study, we describe the MA dimensions and the position of the PMs in a group of normal individuals (n = 38, 60% women, age [mean ± SD] 51 ± 9 years and BSA 1.83 ± 0.16 m2) investigated with transthoracic echocardiography. The anteroposterior dimension (AP) of the ellipse-shaped MA was measured in a parasternal long axis, while the distance from the posteromedial (PoM) to the anterolateral (AL) commissure was measured in a parasternal short axis (CC). The annular area was calculated assuming elliptic geometry. The MA shape was described by the ratios AP/CC and AP/length of the anterior leaflet. The PMs' position was described by the following distances: (a) from the MA to the tip of the PoM and AL, PMs measured in a modified two-chamber view where both PMs could be identified, (b) the interpapillary distance, and (c) the tethering distance from the tip of the PM to the contralateral MA. These data on the normal mitral valve morphology should provide useful information when assessing the underlying mechanism of functional MR. [source] Multifocal structure of the T cell , dendritic cell synapseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2005Cédric Brossard Abstract The structure of immunological synapses formed between murine naive T cells and mature dendritic cells has been subjected to a quantitative analysis. Immunofluorescence images of synapses formed in the absence of antigen show a diffuse synaptic accumulation of CD3 and LFA-1. In electron microscopy, these antigen-free synapses present a number of tight appositions (cleft size ,15,nm), all along the synapse. These tight appositions cover a significantly larger surface fraction of antigen-dependent synapses. In immunofluorescence, antigen-dependent synapses show multiple patches of CD3 and LFA-1 with a variable overlap. A similar distribution is observed for PKC, and talin. A concentric organization characteristic of prototypical synapses is rarely observed, even when dendritic cells are paralyzed by cytoskeletal poisons. In T,DC synapses, the interaction surface is composed of several tens of submicronic contact spots, with no large-scale segregation of CD3 and LFA-1. As a comparison, in T,B synapses, a central cluster of CD3 is frequently observed by immunofluorescence, and electron microscopy reveals a central tight apposition. Our data show that it is inappropriate to consider the concentric structure as a "mature synapse" and multifocal structures as immature. [source] The actin-binding protein profilin I is localized at synaptic sites in an activity-regulated mannerEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005Henrike Neuhoff Abstract Morphological changes at synaptic specializations have been implicated in regulating synaptic strength. Actin turnover at dendritic spines is regulated by neuronal activity and contributes to spine size, shape and motility. The reorganization of actin filaments requires profilins, which stimulate actin polymerization. Neurons express two independent gene products , profilin I and profilin II. A role for profilin II in activity-dependent mechanisms at spine synapses has recently been described. Although profilin I interacts with synaptic proteins, little is known about its cellular and subcellular localization in neurons. Here, we investigated the subcellular distribution of this protein in brain neurons as well as in hippocampal cultures. Our results indicate that the expression of profilin I varies in different brain regions. Thus, in cerebral cortex and hippocampus profilin I immunostaining was associated predominantly with dendrites and was present in a subset of dendritic spines. In contrast, profilin I in cerebellum was associated primarily with presynaptic structures. Profilin I immunoreactivity was partially colocalized with the synaptic molecules synaptophysin, PSD-95 and gephyrin in cultured hippocampal neurons, indicating that profilin I is present in only a subset of synapses. At dendritic spine structures, profilin I was found primarily in protrusions, which were in apposition to presynaptic terminal boutons. Remarkably, depolarization with KCl caused a moderate but significant increase in the number of synapses containing profilin I. These results show that profilin I can be present at both pre- and postsynaptic sites and suggest a role for this actin-binding protein in activity-dependent remodelling of synaptic structure. [source] A Computational Approach on the Osseointegration of Bone Implants Based on a Bio-Active Interface TheoryGAMM - MITTEILUNGEN, Issue 2 2009André Lutz Abstract In this presentation an integrated approach on the simulation of osseointegration in the boneimplant interface is outlined. Besides the consistent combination of computational bone remodelling simulation and established medical imaging techniques, a new model refinement in terms of a bioactive interface theory is introduced, which enables the simulation of bone ingrowth in rough coated uncemented implants. Under consideration of seven physiological loads of daily motion the bone-implant relative micromotion in a soft tissue region around the endoprosthesis is investigated. As the micromotions are an important factor for osseointegration, because excessive micromotion leads to apposition of fibrous tissue, they are considered for the simulation of osseointegration. Results for different parameter constellations, regarding thickness and stiffness of bone-implant interface layer, are compared and the ingrowth for different configurations is predicted. With these results conclusions can be made about the stability of prosthesis in the host bone, which is an important factor for the clinical success of the treatment (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] "Tongue sandwich" bolster for skin graft immobilization,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2002Charles E. Butler MD Abstract Background Because of surface irregularities and continuous movement of the tongue, predictable immobilization of split-thickness skin grafts (STSGs) for tongue defects is difficult to achieve. Methods A novel composite, bilayer foam bolster was used to immobilize a STSG after reconstruction of more than 80% of the tongue mucosa after resection of a squamous cell carcinoma and extensive leukoplakia. Dorsal and ventral bolster components were placed over the STSG and affixed using transglossal, through-and-through sutures. Results The composite foam bolster provided uniform compression along the highly irregular and mobile skin-grafted surface. Graft survival was excellent, and there were no complications. Conclusions The "tongue sandwich" bolster is quickly and easily fabricated, immobilizes the tongue in a fully expanded position, and provides excellent apposition of STSGs to highly irregular and vascular surfaces. © 2002 Wiley Periodicals, Inc. Head Neck 24: 705,709, 2002 [source] Distribution and morphology of serotonin-immunoreactive axons in the hippocampal region of the New Zealand white rabbit.HIPPOCAMPUS, Issue 1 2003Abstract This study provides a detailed light microscopic description of the morphology and distribution of immunohistochemically stained serotonergic axons in the hippocampal region of the New Zealand white rabbit. The serotonergic axons were segregated morphologically into three types: beaded fibers, fine fibers, and stem-axons, respectively. Beaded fibers were thin serotonergic axons with large varicosities, whereas thin axons with small fusiform or granular varicosities were called fine fibers. Finally, thick straight non-varicose axons were called stem-axons. Beaded fibers often formed large conglomerates with numerous boutons (pericellular arrays) in close apposition to the cell-rich layers in the hippocampal region, e.g., the granular and hilar cell layers of the dentate area and the pyramidal cell layer ventrally in CA3. The pericellular arrays in these layers were often encountered in relation to small calbindin-D28K -positive cells, as shown by immunohistochemical double staining for serotonin and calbindin-D28K. The beaded and fine serotonergic fibers displayed a specific innervation pattern in the hippocampal region and were encountered predominantly within the terminal field of the perforant path, e.g., the stratum moleculare hippocampi and the outer two-thirds of the dentate molecular layer. These fibers were also frequently seen in the deep part of the stratum oriens and the alveus, forming a dense plexus in relation to large multipolar calbindin-D28K -positive cells and their basal extensions. Stem-axons were primarily seen in the fimbria and alveus. This innervation pattern was present throughout the entire hippocampal formation, but there were considerable septotemporal differences in the density of the serotonergic innervation. A high density of innervation prevailed in the ventral/temporal part of the hippocampal formation, whereas the dorsal/septal part received only a moderate to weak serotonergic innervation. These results suggest that the serotonergic system could modulate the internal hippocampal circuitry by way of its innervation in the terminal field of the perforant path, the hilus fasciae dentatae, and ventrally in the zone closely apposed to the mossy fiber layer and the pyramidal cells of CA3. This modulation could be of a dual nature, mediated directly by single serotonergic fibers traversing the hippocampal layers or indirectly by the pericellular arrays and their close relation to the calbindin-D28K -positive cells. The marked septotemporal differences in innervation density point toward a difference between the ventral and dorsal parts of the hippocampal formation with respect to serotonergic function and need for serotonergic modulation. Hippocampus 2003;13:21,37. © 2003 Wiley-Liss, Inc. [source] Construction of the Femoral Neck During Growth Determines Its Strength in Old Age,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2007Roger M D Zebaze Abstract Study of the design of the FN in vivo in 697 women and in vitro in 200 cross-sections of different sizes and shapes along each of 13 FN specimens revealed that strength in old age was largely achieved during growth by differences in the distribution rather than the amount of bone material in a given FN cross-section from individual to individual. Introduction: We studied the design of the femoral neck (FN) to gain insight into the structural basis of FN strength in adulthood and FN fragility in old age. Materials and Methods: Studies in vivo were performed using densitometry in 697 women and in vitro using high-resolution ,CT and direct measurements in 13 pairs of postmortem specimens. Results: The contradictory needs of strength for loading yet lightness for mobility were met by varying FN size, shape, spatial distribution, and proportions of its trabecular and cortical bone in a cross-section, not its mass. Wider and narrower FNs were constructed with similar amounts of bone material. Wider FNs were relatively lighter: a 1 SD higher FN volume had a 0.67 (95% CI, 0.61,0.72) SD lower volumetric BMD (vBMD). A 1 SD increment in height was achieved by increasing FN volume by 0.32 (95% CI, 0.25,0.39) SD with only 0.15 (95% CI, 0.08,0.22) SD more bone, so taller individuals had a relatively lighter FN (vBMD was 0.13 [95% CI, 0.05,0.20 SD] SD lower). Greater periosteal apposition constructing a wider FN was offset by even greater endocortical resorption so that the same net amount of bone was distributed as a thinner cortex further from the neutral axis, increasing resistance to bending and lowering vBMD. This was recapitulated at each point along the FN; varying absolute and relative degrees of periosteal apposition and endocortical resorption focally used the same amount of material to fashion an elliptical FN of mainly cortical bone near the femoral shaft to offset bending but a more circular FN of proportionally more trabecular and less cortical bone to accommodate compressive loads adjacent to the pelvis. This structural heterogeneity was largely achieved by adaptive modeling and remodeling during growth,most of the variance in FN volume, BMC, and vBMD was growth related. Conclusions: Altering structural design while minimizing mass achieves FN strength and lightness. Bone fragility may be the result of failure to adapt bone's architecture to loading, not just low bone mass. [source] Thyroid-Stimulating Hormone Restores Bone Volume, Microarchitecture, and Strength in Aged Ovariectomized Rats*,,§JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007T Kuber Sampath PhD Abstract We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. Introduction: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. Materials and Methods: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8,16 wk. Long bones were subjected to ,CT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. Results: In the prevention mode, low doses (0.1 and 0.3 ,g) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 ,g TSH had increased BMD (10,11%), trabecular bone volume (100,130%), trabecular number (25,40%), trabecular thickness (45,60%), cortical thickness (5,16%), mineral apposition and bone formation rate (200,300%), and enhanced mechanical strength of the femur (51,60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. Conclusions: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling. [source] A Novel Tetracycline Labeling Schedule for Longitudinal Evaluation of the Short-Term Effects of Anabolic Therapy With a Single Iliac Crest Bone Biopsy: Early Actions of Teriparatide,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2006Robert Lindsay MD Abstract We describe a quadruple tetracycline labeling method that allows longitudinal assessment of short-term changes in bone formation in a single biopsy. We show that 1 month of hPTH(1-34) treatment extends the bone-forming surface, increases mineral apposition rate, and initiates modeling-based formation. Introduction: Iliac crest biopsy, with histomorphometric evaluation, provides important information about cellular activity in bone. However, to obtain longitudinal information, repeat biopsies must be performed. In this study, we show the capability to obtain short-term longitudinal information on bone formation in a single biopsy using a novel, quadruple labeling technique. Materials and Methods: Two tetracycline labels were administered using a standard 3 days on, 12 days off, 3 days on format. Four weeks later, the tetracycline labeling was repeated using the same schedule but with a different tetracycline that can be distinguished from the first by its color under fluorescent light. Iliac crest biopsies were performed 1 week later and prepared undecalcified for histomorphometry. Indices of bone formation 1 month apart were measured and calculated using the two sets of labels. We used this method to investigate the early effects of teriparatide [hPTH(1-34)] treatment on bone formation. The results were compared with those from a group of control subjects who were quadruple-labeled, but did not receive hPTH(1-34). Results: Treatment with hPTH(1-34) dramatically stimulated bone formation on cancellous and endocortical surfaces. This was achieved by both an increase in the linear rate of matrix apposition and extension of the bone-forming surface. New bone was deposited on previously quiescent surfaces (i.e., modeling-based formation), but a proportion of this could occur by encroachment from adjacent resorption cavities. Conclusions: A single transiliac crest bone biopsy, after sequential administration of two sets of tetracycline labels is a useful approach to study the short-term effects of anabolic agents on human bone. One month of hPTH(1-34) treatment extends the bone-forming surface, increases mineral apposition rate, and initiates modeling-based formation. [source] Low Skeletal Muscle Mass Is Associated With Poor Structural Parameters of Bone and Impaired Balance in Elderly Men,The MINOS Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2005Pawel Szulc MD Abstract In 796 men, 50-85 years of age, decreased relative skeletal muscle mass index was associated with narrower bones, thinner cortices, and a consequent decreased bending strength (lower section modulus), as well as with impaired balance and an increased risk of falls. Introduction: In men, appendicular skeletal muscle mass (ASM) is correlated positively with BMC and areal BMD (aBMD). In elderly men, low muscle mass and strength (sarcopenia) is associated with difficulties in daily living activities. The aim of this study was to evaluate if ASM is correlated with bone size, mechanical properties of bones, balance, and risk of falls in elderly men. Materials and Methods: This study used 796 men, 50-85 years of age, belonging to the MINOS cohort. Lifestyle factors were evaluated by standardized questionnaires. Estimates of mechanical bone properties were derived from aBMD measured by DXA. ASM was estimated by DXA. The relative skeletal muscle mass index (RASM) was calculated as ASM/(body height)2.3. Results: After adjustment for age, body size, tobacco smoking, professional physical activity, and 17,-estradiol concentration, RASM was correlated positively with BMC, aBMD, external diameter, and cortical thickness (r = 0.17-0.34, p < 0.0001) but not with volumetric BMD. Consequently, RASM was correlated with section modulus (r = 0.29-0.39, p < 0.0001). Men in the lowest quartile of RASM had section modulus of femoral neck and distal radius lower by 12-18% in comparison with men in the highest quartile of RASM. In contrast, bone width was not correlated with fat mass, reflecting the load of body weight (except for L3), which suggests that the muscular strain may exert a direct stimulatory effect on periosteal apposition. After adjustment for confounding variables, a decrease in RASM was associated with increased risk of falls and of inability to accomplish clinical tests of muscle strength, static balance, and dynamic balance (odds ratio per 1 SD decrease in RASM, 1.31-2.23; p < 0.05-0.001). Conclusions: In elderly men, decreased RASM is associated with narrower bones and thinner cortices, which results in a lower bending strength. Low RASM is associated with impaired balance and with an increased risk of falls in elderly men. It remains to be studied whether low RASM is associated with decreased periosteal apposition and with increased fracture risk in elderly men, and whether the difference in skeletal muscle mass between men and women contributes to the between-sex difference in fracture incidence. [source] ,-Arrestin2 Regulates the Differential Response of Cortical and Trabecular Bone to Intermittent PTH in Female Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2005Mary L Bouxsein PhD Abstract Cytoplasmic arrestins regulate PTH signaling in vitro. We show that female ,-arrestin2,/, mice have decreased bone mass and altered bone architecture. The effects of intermittent PTH administration on bone microarchitecture differed in ,-arrestin2,/, and wildtype mice. These data indicate that arrestin-mediated regulation of intracellular signaling contributes to the differential effects of PTH at endosteal and periosteal bone surfaces. Introduction: The effects of PTH differ at endosteal and periosteal surfaces, suggesting that PTH activity in these compartments may depend on some yet unidentified mechanism(s) of regulation. The action of PTH in bone is mediated primarily by intracellular cAMP, and the cytoplasmic molecule ,-arrestin2 plays a central role in this signaling regulation. Thus, we hypothesized that arrestins would modulate the effects of PTH on bone in vivo. Materials and Methods: We used pDXA, ,CT, histomorphometry, and serum markers of bone turnover to assess the skeletal response to intermittent PTH (0, 20, 40, or 80 ,g/kg/day) in adult female mice null for ,-arrestin2 (,-arr2,/,) and wildtype (WT) littermates (7-11/group). Results and Conclusions: ,-arr2,/, mice had significantly lower total body BMD, trabecular bone volume fraction (BV/TV), and femoral cross-sectional area compared with WT. In WT females, PTH increased total body BMD, trabecular bone parameters, and cortical thickness, with a trend toward decreased midfemoral medullary area. In ,-arr2,/, mice, PTH not only improved total body BMD, trabecular bone architecture, and cortical thickness, but also dose-dependently increased femoral cross-sectional area and medullary area. Histomorphometry showed that PTH-stimulated periosteal bone formation was 2-fold higher in ,-arr2,/, compared with WT. Osteocalcin levels were significantly lower in ,-arr2,/, mice, but increased dose-dependently with PTH in both ,-arr2,/, and WT. In contrast, whereas the resorption marker TRACP5B increased dose-dependently in WT, 20-80 ,g/kg/day of PTH was equipotent with regard to stimulation of TRACP5B in ,-arr2,/,. In summary, ,-arrestin2 plays an important role in bone mass acquisition and remodeling. In estrogen-replete female mice, the ability of intermittent PTH to stimulate periosteal bone apposition and endosteal resorption is inhibited by arrestins. We therefore infer that arrestin-mediated regulation of intracellular signaling contributes to the differential effects of PTH on cancellous and cortical bone. [source] Drugs Used to Treat Osteoporosis: The Critical Need for a Uniform Nomenclature Based on Their Action on Bone Remodeling,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2005B Lawrence Riggs MD Abstract There continues to be uncertainty about the classification of available drugs for treating osteoporosis. We find that grouping them into anti-catabolic and anabolic classes based on the mechanisms of their action on bone remodeling and fracture reduction removes ambiguities and provides a relatively straightforward classification. The recent introduction of teriparatide into clinical practice initiated the era of anabolic therapy for osteoporosis, but it is still unclear how to define an anabolic drug. All drugs that increase bone mass do so by affecting bone remodeling. When their mechanisms of action on bone remodeling and on fracture reduction are considered, we find that anti-osteoporotic drugs fall naturally into either anti-catabolic or anabolic classes. Anti-catabolic drugs increase bone strength and reduce fractures mainly by decreasing the number of bone multicellular units (BMUs). This reduces perforative resorption and preserves skeletal microarchitecture (by preventing further structural damage to trabecular bone and increased porosity in cortical bone induced by high bone remodeling). Reduction in bone remodeling by anti-catabolic drugs may increase bone mass moderately during the interval in which previously initiated BMUs are completing mineralization. Some anti-catabolic drugs may also enhance the formation phase of the remodeling cycle, but their major action is to reduce overall bone turnover (i.e., the number of BMUs in bone). In contrast, anabolic drugs increase bone strength and reduce fractures by substantially increasing bone mass as a result of an overall increase in the number of BMUs combined with a positive BMU balance (the magnitude of the formation phase is greater than that of the resorption phase). Some anabolic drugs also induce renewed modeling, increase periosteal apposition and repair of trabecular microstructure. We hope that this classification will serve as a starting point for continued discussion on the important issue of nomenclature. [source] Localization of the membrane-anchored MMP-regulator RECK at the neuromuscular junctionsJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Satoshi Kawashima Abstract Nerve apposition on nicotinic acetylcholine receptor clusters and invagination of the post-synaptic membrane (i.e. secondary fold formation) occur by embryonic day 18.5 at the neuromuscular junctions (NMJs) in mouse skeletal muscles. Finding the molecules expressed at the NMJ at this stage of development may help elucidating how the strong linkage between a nerve terminal and a muscle fiber is established. Immunohistochemical analyses indicated that the membrane-anchored matrix metalloproteinase regulator RECK was enriched at the NMJ in adult skeletal muscles. Confocal and electron microscopy revealed the localization of RECK immunoreactivity in secondary folds and subsynaptic intracellular compartments in muscles. Time course studies indicated that RECK immunoreactivity becomes associated with the NMJ in the diaphragm at around embryonic day 18.5 and thereafter. These findings, together with known properties of RECK, support the hypothesis that RECK participates in NMJ formation and/or maintenance, possibly by protecting extracellular components, such as synaptic basal laminae, from proteolytic degradation. [source] Seeking long-term relationship: axon and target communicate to organize synaptic differentiationJOURNAL OF NEUROCHEMISTRY, Issue 5 2006Michael A. Fox Abstract Synapses form after growing axons recognize their appropriate targets. The subsequent assembly of aligned pre and postsynaptic specializations is critical for synaptic function. This highly precise apposition of presynaptic elements (i.e. active zones) to postsynaptic specializations (i.e. neurotransmitter receptor clusters) strongly suggests that communication between the axon and target is required for synaptic differentiation. What trans-synaptic factors drive such differentiation at vertebrate synapses? First insights into the answers to this question came from studies at the neuromuscular junction (NMJ), where axon-derived agrin and muscle-derived laminin ,2 induce post and presynaptic differentiation, respectively. Recent work has suggested that axon- and target-derived factors similarly drive synaptic differentiation at central synapses. Specifically, WNT-7a, neuroligin, synaptic cell adhesion molecule (SynCAM) and fibroblast growth factor-22 (FGF-22) have all been identified as target-derived presynaptic organizers, whereas axon-derived neuronal activity regulated pentraxin (Narp), ephrinB and neurexin reciprocally co-ordinate postsynaptic differentiation. In addition to these axon- and target-derived inducers of synaptic differentiation, factors released from glial cells have also been implicated in regulating synapse assembly. Together, these recent findings have profoundly advanced our understanding of how precise appositions are established during vertebrate nervous system development. [source] Serotonergic and Catecholaminergic Interactions with Co-Localised Dopamine-Melatonin Neurones in the Hypothalamus of the Female TurkeyJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2009S. W. Kang Serotonin and catecholamines (dopamine, norepinephrine, epinephrine) have important roles as neurotransmitters in avian reproduction, but their anatomical relationship to the neuroendocrine circuitry that regulates reproduction is poorly understood. Our previous studies have shown that co-localised dopamine-melatonin (DA-MEL) neurones in the avian premammillary nucleus (PMM) are active during periods of photoresponsiveness and, therefore, are potentially photosensitive neurones. Because serotonergic and catecholaminergic neurotransmitters are important regulators of reproductive function in the female turkey, we hypothesised that the serotonergic/catecholaminergic neurones within the brainstem might interact with PMM DA-MEL neurones and constitute an important circuit for reproductive function. To examine this possible interaction, the retrograde fluorescent tract tracer, 1,1,dioctadecyl-3,3,3,3,-tetramethyleindocarbocyanine perchlorate (DiI) was injected into the PMM, and combined with serotonin, tyrosine hydroxylase (TH), dopamine ,-hydroxylase (DBH) and phenyl N -methyltransferse (PNMT) immunocytochemistry to reveal neuroanatomical connections. Changes in the activities of serotonergic, dopaminergic, adrenergic and noradrenergic neuronal systems projecting to the PMM were measured at different reproductive states with in situ hybridisation (ISH) techniques, using tryptophan hydroxylase 2 (TPH2) and TH mRNA expression, respectively. Cells labelled with DiI were found in anatomically discrete areas in or near the hypothalamus and the brainstem. Double immunocytochemistry confirmed that there were serotonin, DBH and PNMT fibres in close apposition to DA-MEL neurones. TPH2 mRNA expression in serotonin neurones was found in several nuclei, and its most abundant mRNA expression was seen in the nucleus Locus ceruleus of laying and incubating hens. TH mRNA expression levels in the six catecholaminegic areas labelled with DiI was measured across the different reproductive states. In the nucleus tractus solitarius (adrenergic), the highest level of TH mRNA expression was found in photorefractory hens and the lowest level in incubating hens. These observed patterns of serotonin/catecholamine neuronal distribution and their variable interactions with PMM DA-MEL neurones during different reproductive states may offer a significant neuroanatomical basis for understanding the control of avian reproductive seasonality. [source] Morphological Evidence for Direct Interaction Between Gonadotrophin-Releasing Hormone Neurones and Astroglial Cells in the Human HypothalamusJOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2007M. Baroncini In rodents, there is compelling evidence indicating that dynamic cell-to-cell communications involving cross talk between astroglial cells (such as astrocytes and specialised ependymoglial cells known as tanycytes) and neurones are important in regulating the secretion of gonadotrophin-releasing hormone (GnRH), the neurohormone that controls both sexual maturation and adult reproductive function. However, whether such astroglial cell,GnRH neurone interactions occur in the human brain is not known. In the present study, we used immunofluorescence to examine the anatomical relationship between GnRH neurones and glial cells within the hypothalamus of five women. Double-staining experiments demonstrated the ensheathment of GnRH neurone perikarya by glial fibrillary acidic protein (GFAP)-immunoreactive astrocyte processes in the periventricular zone of the tuberal region of the hypothalamus. GFAP immunoreactivity did not overlap that of GnRH at the GnRH neurone's projection site (i.e. the median eminence of the hypothalamus). Rather, human GnRH neuroendocrine fibres were found to be closely associated with vimentin or nestin-immunopositive radial gial processes likely belonging to tanycytes. In line with these light microscopy data, ultrastructural examination of GnRH-immunoreactive neurones showed numerous glial cells in direct apposition to pre-embedding-labelled GnRH cell bodies and/or dendrites in the infundibular nucleus, whereas postembedding immunogold-labelled GnRH nerve terminals were often seen to be enwrapped by glial cell processes in the median eminence. GnRH nerve button were sometimes visualised in close proximity to fenestrated pituitary portal blood capillaries and/or evaginations of the basal lamina that delineate the pericapillary space. In summary, these data demonstrate that GnRH neurones morphologically interact with astrocytes and tanycytes in the human brain and provide evidence that glial cells may contribute physiologically to the process by which the neuroendocrine brain controls the function of GnRH neurones in humans. [source] Early healing of flexor tendon insertion site injuries: Tunnel repair is mechanically and histologically inferior to surface repair in a canine modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2006Matthew J. Silva Abstract Orthopedic injuries often require surgical reattachment of tendon to bone. Tendon ends can be sutured to bone by direct apposition to the bone surface or by placement within a bone tunnel. Our objective was to compare early healing of a traditional surface versus a novel tunnel method for repair of the flexor digitorum profundus (FDP) tendon insertion site in a canine model. A total of 70 tendon,bone specimens were analyzed 0, 5, 10 or 21 days after injury and repair, using tensile and range of motion mechanical testing, histology and densitometry. Ultimate force (a measure of repair strength) did not differ between surface and tunnel repairs at day 0. Both repair types had reduced strength at 10 and 21 days compared to 0 days, indicative of deterioration of suture grasping strength (tendon softening). At 21 days, tendons repaired in a bone tunnel had 38% lower ultimate force compared to surface repairs (p,=,0.017). Histological findings were comparable between repair groups at 5 and 10 days but differed at 21 days, when we saw evidence of maturation of the tendon,bone interface in the surface repairs compared to an immature fibrous interface with no evidence of tendon,bone integration in the tunnel repairs. After accounting for bone removed by the tunnel, no difference in bone mineral density or trabecular bone volume existed between surface and tunnel repairs. If the results of our animal study extend to healing of the human FDP insertion, they indicate that FDP tendons should be reattached to the distal phalanx by suture to the cortical surface rather than suture in a bone tunnel. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Bone tissue engineering in a critical size defect compared to ectopic implantations in the goatJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2004Moyo C. Kruyt Abstract Since the application of the autologous bone graft, the need for an alternative has been recognized. Tissue engineering (TE) of bone by combining bone marrow stromal cells (BMSCs) with a porous scaffold, is considered a promising technique. In this study we investigated the potential of tissue engineered bone to heal a critical sized defect in the goat. Orthotopic bone formation was compared to ectopic bone formation in comparable constructs. TE constructs were prepared from goat BMSCs and porous biphasic calcium phosphate ceramic scaffolds. These constructs and scaffolds without cells were implanted paired in critical sized iliac wing defects. Comparable samples were implanted intramuscularly. After 9 (n = 7) and 12 (n = 8) weeks implantation, the samples were analyzed histomorphometrically. After 9-weeks implantation in the iliac wing defect, significantly more bone apposition was found in the TE condition. After 12 weeks, the defects were almost completely filled with bone, but no significant advantage of TE was determined anymore. This contrasted with the intramuscular samples where TE implants showed significantly more bone at both time points. In conclusion, bone TE is feasible in critical sized defects. However, when appropriate osteoconductive/inductive materials are applied the effect of cell seeding may be temporary. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Macrophage-Related Demyelination In Peripheral Nerves Of Mice Deficient In The Gap Junction Protein Connexin 32JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2002I Kobsar Mice deficient in the gap junction protein connexin 32 (Cx32) develop a slowly progressing demyelinating neuropathy, with enlarged periaxonal collars, abnormal non-compacted myelin domains and axonal sprouts. These mice serve as a model for the X-linked form of inherited demyelin- ating neuropathies in humans. Based on our previous findings that macrophages are involved in demyelination in other myelin mutants (i.e. mice heterozygously deficient in P0), we considered the possibility that macrophages might be also mediators of demyelination in Cx32-deficient mice. Indeed, we detected an age-related increase in the number of macrophages in demyelinating nerves of Cx32-deficient mice. In addition, immunoelectron microscopy revealed macrophages in an apposition to degenerating myelin reminiscent of a macrophage-mediated demyelinating neuropathy. We conclude that involvement of macrophages might be a widespread phenomenon in genetically-determined demyelination. [source] Early ontogeny and placentation of the grey short-tailed opossum, Monodelphis domestica (Didelphidae: Marsupialia): contribution to the reconstruction of the marsupial morphotypeJOURNAL OF ZOOLOGICAL SYSTEMATICS AND EVOLUTIONARY RESEARCH, Issue 3 2001Zeller This study provides new findings on the placenta of Monodelphis domestica and a reconstruction of the marsupial morphotype. To achieve this, early ontogeny and placentation of the grey short-tailed opossum, M. domestica, from 3 h after copulation until birth (day 15), were studied and compared with other mammals. Both the ultrastructure and histochemistry of egg membranes, foetal membranes, oviduct and uterus were examined. The results of this study provide the first detailed ultrastructural description of a trophoblastic syncytium in a marsupial. In addition, this is the first original documentation of an invasive trophectoderm and an inflammatory reaction at parturition in M. domestica. These findings were compared with literature data and included into the reconstruction of the marsupial morphotype. Based on marsupial phylogeny as proposed by Luckett (J. Mammal. Evol. 2, 255,283, 1994), characters that are consistent at least within didelphids and dasyurids were determined to be characters of the marsupial morphotype. These characters are a central yolk separated from the peripheral yolk-poor cytoplasm in the unfertilized oocyte, the presence of a zona pellucida, a mucoid coat and a shell coat, the absence of a corona radiata, oviductal mucoid secretion, no shell secretion distal to the isthmus of the oviduct, uterine shell secretion, a short tubal passage (1 day at maximum), the apposition of blastomeres to the zona pellucida prior to intercellular association, the absence of a morula stage, the polarity of the zygotic yolk, the localized segmentation of deutoplasm (yolk) during the first cleavage and subsequent extrusion of yolk vesicles during the first two cleavage stages. With regard to the marsupial morphotype, the non-polarized yolk distribution in the zygote [Hartman (J. Morphol. 27, 1,84, 1916); McCrady (Am. Anat. Mem. 16, 1,233, 1938)] is a derived character of Didelphis virginiana. Didelphis virginiana [Hartman (J. Morphol. 27, 1,84, 1916); Hartman (J. Morphol. 32, 1,139, 1919); McCrady (Am. Anat. Mem. 16, 1,233, 1938)] and Didelphis marsupialis (Hill, Q. J. Micr. Sci. 63, 91,139, 1918) share the synapomorphous reduction of deutoplasmolysis to a generalized extrusion of vesicles. The absence of separated yolk and consequently a cleavage without yolk extrusion (Renfree and Lewis, Reprod. Fert. Dev. 8, 725,742, 1996) are apomorphies of macropodids. This is possibly correlated with the association of blastomeres in early cleavage stages (Renfree and Lewis, Reprod. Fert. Dev. 8, 725,742, 1996). A yolk sac placenta and a vascularized allantochorion can be assumed for part of the ontogeny in the marsupial morphotype, irrespective of the formation of an allantoic placenta at near term stages. The character polarization of the mode of placentation and parturition needs further investigation. Frühe Ontogenie und Plazentation der grauen Hausspitzmausbeutelratte, Monodelphis domestica (Didelphidae: Marsupialia): Ein Beitrag zur Rekonstruktion des Grundplans der Marsupialia Die vorliegende Arbeit beschreibt die frühe Ontogenese und Plazentation von 3 Stunden nach der Kopulation bis zur Geburt der Beutelratte Monodelphis domestica. Es wird die Ultrastruktur und Histochemie der Eihäute, der Fetalmembranen, des Oviductes und des Uterus beschrieben. Erstmalig wird die Ultrastruktur eines trophoblastischen Syncytiums bei einem Beuteltier beschrieben. Weiterhin wird ein invasives Trophektoderm und eine Entzündungsreaktion zum Zeitpunkt der Geburt bei M. domestica festgestellt. Die Befunde dieser Studie und Literaturdaten werden verglichen und in eine Grundplanrekonstruktion integriert. Merkmale, die mindestens zwischen Vertretern der Didelphidae und Dasyuridae übereinstimmen, werden basierend auf dem phylogenetischen System der Marsupialia nach Luckett, J. Mammal. Evol. 2, 255,283, 1994, für den Grundplan der Marsupialia angenommen. Diese Merkmale sind zentral separierter Dotter und peripheres dotterarmes Zytoplasma in der unbefruchteten Eizelle, das Vorhandensein von Zona pellucida, Mucoidschicht und Schalenhaut, das Fehlen einer Corona radiata, die Mucoidsekretion durch den Oviduct, die Schalensekretion durch den Uterus und nicht distal der Isthmusregion des Oviductes, eine kurze Tubenwanderung (maximal einen Tag), die Anlagerung der Blastomeren an die Zona pellucida vor der interzellulären Verbindung, das Fehlen eines Morulastadiums, die Dotterpolarität in der Zygote, die lokale Dotterabtrennung bei der ersten Teilung und die anschließende Dotterextrusion während der ersten beiden Teilungen. In Bezug auf den Grundplan der Marsupialia ist die unpolare Dotterverteilung in der Zygote ein abgeleitetes Merkmal von Didelphis virginiana. Didelphis virginiana und Didelphis marsupialis teilen als Synapomorphie die Reduktion der Deutoplasmolyse auf eine generelle Vesikelextrusion. Das Fehlen separierten Dotters in der Oocyte und die resultierende Furchung ohne Dotterextrusion [Renfree and Lewis, Reprod. Fert. Dev. 8, 725,742, 1996] ist eine Apomorphie der Macropodidae. Hiermit hängt möglicherweise die frühe Zusammenlagerung der Blastomeren zusammen [Renfree and Lewis, Reprod. Fert. Dev. 8, 725,742, 1996]. Ein vaskularisiertes Allantochorion und eine Dottersackplazenta können für einen Teil der Ontogenese im Grundplan der Marsupialia angenommen werden. Ob das Allantochorion neben der Respiration auch dem Stoffaustausch diente ist unklar. Die Lesrichtung für den Modus der Plazentation und der Geburt bedarf weiterer Untersuchungen. [source] Ultrastructural evidence for communication between intramuscular vagal mechanoreceptors and interstitial cells of Cajal in the rat fundusNEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2008T. L. Powley Abstract, To assess whether afferent vagal intramuscular arrays (IMAs), putative gastrointestinal mechanoreceptors, form contacts with interstitial cells of Cajal of the intramuscular type (ICC-IM) and to describe any such contacts, electron microscopic analyses were performed on the external muscle layers of the fundus containing dextran-labelled diaminobenzidin (DAB)-stained IMAs. Special staining and embedding techniques were developed to preserve ultrastructural features. Within the muscle layers, IMA varicosities were observed in nerve bundles traversing major septa without contact with ICC-IM, contacting unlabelled neurites and glial cells. IMA varicosities were encountered in minor septa in contact with ICC-IM which were not necessarily in close contact with muscle cells. In addition, IMA varicosities were observed within muscle bundles in close contact with ICC-IM which were in gap junction contact with muscle cells. IMAs formed varicosities containing predominantly small agranular vesicles, occasionally large granular vesicles and prejunctional thickenings in apposition to ICC-IM processes, indicating communication between ICC and IMA via synapse-like contacts. Taken together, these different morphological features are consistent with a hypothesized mechanoreceptor role for IMA-ICC complexes. Intraganglionic laminar ending varicosities contacted neuronal somata and dendrites in the myenteric plexus of the fundus, but no contacts with ICC associated with Auerbach's plexus were encountered. [source] Affinity of corpora amylacea for oligonucleotides: Sequence dependency and proteinaceous binding motifNEUROPATHOLOGY, Issue 4 2006Ioan A. Balea Corpora amylacea (CA) have an affinity to nucleic acids as shown by in situ hybridization experiments. However, little is known about the specificity of this interaction, as well as the mechanism involved. We investigated the ability of different probes of digoxigenin-labeled oligonucleotides corresponding to some specific neuronal receptors, both sense and antisense, to bind to CA from human autopsy brain tissue. The bound nucleotides were detected with antidigoxigenin antibody and the signal was further amplified using the tyramide signal amplification system. The affinity of binding varies with the sequence of nucleotides. The most intense signal is produced by the adenosine-2A receptor antisense probe and the least intense signal is produced by the N-methyl-D-aspartate receptor sense probe. The affinity of binding for the same probe does not depend on the localization of CA in the central nervous system. Complete staining loss by proteinase K pretreatment in higher concentrations shows that the binding motif is partially proteinaceous. The circumferential but not the punctate internal staining is diminished by mild amylglucosidase pretreatment, suggesting a process of progressive apposition and condensation. [source] Tails of the unexpected: palatal medial edge epithelium is no more specialized than other embryonic epitheliumORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 1 2007NL Brown Structured Abstract Authors ,, Brown NL, Sandy JR Objective ,, To determine whether palatal medial edge epithelium (MEE) is specialized in its ability to disappear compared with other embryonic, non-palatal, epithelium. Subjects ,, Embryonic tissues harvested from CD1 mice. Methods ,, Organs were cultured in 2 ml of DMEM/F12 supplemented with 300 ,g/ml l-glutamine and 1% penicillin/streptomycin. Organs were cultured under various conditions including opposing other organs and opposing an inert material for a period of 6 days. Tissues were then processed for histological examination. Results ,, MEE of shelves opposing nothing persisted, whereas MEE of shelves contacting another shelf disappeared. When a tail was placed against a palatal shelf the MEE disappeared, as did the epithelium from the tail, resulting in fusion between the shelf and tail. Furthermore, when palatal shelves were placed against an inert material the MEE disappeared, suggesting pressure alone is a sufficient stimulus to initiate disappearance of the MEE, and that the interaction between the two palatal shelves is not a prerequisite for the disappearance of MEE. Moreover, when two embryonic tails were cultured in close apposition they fused, as did paired limbs. Non-palatal epithelia also disappeared after contact with inert materials. Epithelial disappearance began within 24 h of contact, but there was an age limit. Conclusion ,, These findings suggest that embryonic epithelium from non-specific sites around the body has the ability to disappear with mechanical contact resulting in fusion of tissues. MEE may not be as specialized as once thought. [source] The effects of total hip arthroplasty on the structural and biomechanical properties of adult boneAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 2 2009Joshua J. Peck Abstract The responsiveness of bone to mechanical stimuli changes throughout life, with adaptive potential generally declining after skeletal maturity is reached. This has led some to question the importance of bone functional adaptation in the determination of the structural and material properties of the adult skeleton. A better understanding of age-specific differences in bone response to mechanical loads is essential to interpretations of long bone adaptation. The purpose of this study is to examine how the altered mechanical loading environment and cortical bone loss associated with total hip arthroplasty affects the structural and biomechanical properties of adult bone at the mid-shaft femur. Femoral cross sections from seven individuals who had undergone unilateral total hip arthroplasty were analyzed, with intact, contralateral femora serving as an approximate internal control. A comparative sample of individuals without hip prostheses was also included in the analysis. Results showed a decrease in cortical area in femora with prostheses, primarily through bone loss at the endosteal envelope; however, an increase in total cross-sectional area and maintenance of the parameters of bone strength, Ix, Iy, and J, were observed. No detectable differences were found between femora of individuals without prostheses. We interpret these findings as an adaptive response to increased strains caused by loading a bone previously diminished in mass due to insertion of femoral prosthesis. These results suggest that bone accrued through periosteal apposition may serve as an important means by which adult bone can functional adapt to changes in mechanical loading despite limitations associated with senescence. Am J Phys Anthropol 2009. © 2008 Wiley-Liss, Inc. [source] Vasculogenesis of the embryonic heart: Origin of blood island-like structuresTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 3 2006Anna Ratajska Abstract The earliest vascular structures (blood island-like) in the embryonic heart are clusters of angioblasts and nucleated red blood cells (NRBCs), which differentiate into endothelial cells and erythrocytes, respectively. Our purpose was to define the area and chronology of NRBC appearance in the mouse embryonic heart at the stages before a patency between coronary vessels and peripheral circulation is established (10.5,13.5 dpc). Before and at the onset of vascularization, NBCs were not present within the proepicardium; however, Ter/119+ differentiating erythroblasts and single scattered CD45+ were found in the heart beginning from 10.5 dpc. The Ter/119+ cells were in close apposition to angioblasts (PECAM1+) and were recognized as components of blood island-like structures or vascular vesicles in transmission electron microscope and were located mostly in the subepicardium. Some of the NRBCs were not accompanied by angioblasts and located close to the endocardial endothelium or at the border of the endocardial endothelium or in the subepicardium. These erythroblasts were beginning to assemble with angioblasts. CD34+ NBCs as well as progenitor cells of erythroid lineage were not detected in the heart at these stages of development. The state of differentiation of NRBCs of blood islands was similar/the same as the morphology of circulating blood cells at the respective stages of embryo development. The presence of mature NRBCs in the subendocardial area and lack of progenitor cells of erythroid lineage within the heart indicate that erythroid commitment occurs outside the heart. We suggest that NRBCs enter the heart from the blood stream at 10.5,12 dpc independently from angioblasts. © 2006 Wiley-Liss, Inc. [source] Synaptic specializations exist between enteric motor nerves and interstitial cells of Cajal in the murine stomachTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2005Elizabeth A.H. Beckett Abstract Autonomic neurotransmission is thought to occur via a loose association between nerve varicosities and smooth muscle cells. In the gastrointestinal tract ultrastructural studies have demonstrated close apposition between enteric nerves and intramuscular interstitial cells of Cajal (ICC-IM) in the stomach and colon and ICC in the deep muscular plexus (ICC-DMP) of the small intestine. In the absence of ICC-IM, postjunctional neural responses are compromised. Although membrane specializations between nerves and ICC-IM have been reported, the molecular identity of these specializations has not been studied. Here we have characterized the expression and distribution of synapse-associated proteins between nerve terminals and ICC-IM in the murine stomach. Transcripts for the presynaptic proteins synaptotagmin, syntaxin, and SNAP-25 were detected. Synaptotagmin and SNAP-25-immunopositive nerve varicosities were concentrated in varicose regions of motor nerves and were closely apposed to ICC-IM but not smooth muscle. W/WV mice were used to examine the expression and distribution of synaptic proteins in the absence of ICC-IM. Transcripts encoding synaptotagmin, syntaxin, and SNAP-25 were detected in W/WV tissues. In the absence of ICC-IM, synaptotagmin and SNAP-25 were localized to nerve varicosities. Reverse transcriptase polymer chain reaction (RT-PCR) and immunohistochemistry demonstrated the expression of postsynaptic density proteins PSD-93 and PSD-95 in the stomach and expression levels of PSD-93 and PSD-95 were reduced in W/WV mutants. These data support the existence of synaptic specializations between enteric nerves and ICC-IM in gastric tissues. In the absence of ICC-IM, components of the synaptic vesicle docking and fusion machinery is trafficked and concentrated in enteric nerve terminals. J. Comp. Neurol. 493:193,206, 2005. © 2005 Wiley-Liss, Inc. [source] NPP1, a Phytophthora -associated trigger of plant defense in parsley and ArabidopsisTHE PLANT JOURNAL, Issue 3 2002Guido Fellbrich Summary Activation of non-cultivar-specific plant defense against attempted microbial infection is mediated through the recognition of pathogen-derived elicitors. Previously, we have identified a peptide fragment (Pep-13) within a 42-kDa cell wall transglutaminase from various Phytophthora species that triggers a multifacetted defense response in parsley cells. Many of these oomycete species have now been shown to possess another cell wall protein (24 kDa), that evoked the same pattern of responses in parsley as Pep-13. Unlike Pep-13, necrosis-inducing Phytophthora protein 1 (NPP1) purified from P. parasitica also induced hypersensitive cell death-like lesions in parsley. NPP1 structural homologs were found in oomycetes, fungi, and bacteria, but not in plants. Structure,activity relationship studies revealed the intact protein as well as two cysteine residues to be essential for elicitor activity. NPP1-mediated activation of pathogen defense in parsley does not employ the Pep-13 receptor. However, early induced cellular responses implicated in elicitor signal transmission (increased levels of cytoplasmic calcium, production of reactive oxygen species, MAP kinase activation) were stimulated by either elicitor, suggesting the existence of converging signaling pathways in parsley. Infiltration of NPP1 into leaves of Arabidopsis thaliana Col-0 plants resulted in transcript accumulation of pathogenesis-related (PR) genes, production of ROS and ethylene, callose apposition, and HR-like cell death. NPP1-mediated induction of the PR1 gene is salicylic acid-dependent, and, unlike the P. syringae pv. tomato DC3000(avrRpm1)-induced PR1 gene expression, requires both functional NDR1 and PAD4. In summary, Arabidopsis plants infiltrated with NPP1 constitute an experimental system that is amenable to forward genetic approaches aiming at the dissection of signaling pathways implicated in the activation of non-cultivar-specific plant defense. [source] | ||||||||||||||||||||||||||||