Accepted............................................................................................................. With the Wide Field Planetary Camera 2 (WFPC2) on the Hubble Space Telescope, we have discovered in M4 (NGC 6121, C... more
Accepted............................................................................................................. With the Wide Field Planetary Camera 2 (WFPC2) on the Hubble Space Telescope, we have discovered in M4 (NGC 6121, C 1620-264) the first extensive sequence of cooling white dwarfs seen in a globular cluster. Adopting a distance modulus of (m 0 M)V = 12.65 and a reddening of E(B 0 V) = 0.37, we show that the sequence, which extends over 9 < MU < 13, is comprised of white dwarfs of mass 0:5M. The total mass loss from the present turnoff to the white dwarf sequence is 0:31M and the intrinsic dispersion in the mean mass appears to be < 0.05 M. Both the location of the white dwarf cooling sequence in the cluster color-magnitude diagram and the cumulative luminosity function attest to
The reaggregation of dissociated cells to form organotypic structures provides an in vitro system for the analysis of the cellular interactions and molecular mechanisms involved in the formation of tissue architecture. The retina, an... more
The reaggregation of dissociated cells to form organotypic structures provides an in vitro system for the analysis of the cellular interactions and molecular mechanisms involved in the formation of tissue architecture. The retina, an outgrowth of the forebrain, is a precisely layered neural tissue, yet the mechanisms underlying layer formation are largely unexplored. Here we describe the protocol to dissociate, re-aggregate, and culture zebrafish retinal cells from a transgenic, Spectrum of Fates, line where all main cell types are labelled with a combination of fluorescent proteins driven by fate-specific promoters. These cells re-aggregate and self-organize in just 48 h in minimal culture conditions. We also describe how the patterning in these aggregates can be analyzed using isocontour profiling to compare whether different conditions affect their self-organization.
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To investigate the cell-cell interactions necessary for the formation of retinal layers, we cultured dissociated zebrafish retinal progenitors in agarose microwells. Within these wells, the cells re-aggregated within hours, forming tight... more
To investigate the cell-cell interactions necessary for the formation of retinal layers, we cultured dissociated zebrafish retinal progenitors in agarose microwells. Within these wells, the cells re-aggregated within hours, forming tight retinal organoids. Using a Spectrum of Fates zebrafish line, in which all different types of retinal neurons show distinct fluorescent spectra, we found that by 48 hours in culture, the retinal organoids acquire a distinct spatial organization, i.e. they became coarsely but clearly laminated. Retinal pigment epithelium cells were in the centre, photoreceptors and bipolar cells were next most central and amacrine cells and retinal ganglion cells were on the outside. Image analysis allowed us to derive quantitative measures of lamination, which we then used to find that Müller glia, but not RPE cells, are essential for this process.
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The Nuclear receptor subfamily 4 group A member 2 (Nr4a2) is crucial for the formation or maintenance of dopaminergic neurons in the central nervous system including the retina, where dopaminergic amacrine cells contribute to visual... more
The Nuclear receptor subfamily 4 group A member 2 (Nr4a2) is crucial for the formation or maintenance of dopaminergic neurons in the central nervous system including the retina, where dopaminergic amacrine cells contribute to visual function. Little is known about which cells express Nr4a2 at which developmental stage. Furthermore, whether Nr4a2 functions in combination with other genes is poorly understood. Thus, we generated a novel transgenic to visualise Nr4a2 expression in vivo during zebrafish retinogenesis. A 4.1 kb fragment of the nr4a2a promoter was used to drive green fluorescent protein expression in this Tg(nr4a2a:eGFP) line. In situ hybridisation showed that transgene expression follows endogenous RNA expression at a cellular level. Temporal expression and lineages were quantified using in vivo time-lapse imaging in embryos. Nr4a2 expressing retinal subtypes were characterised immunohistochemically. Nr4a2a:eGFP labelled multiple neuron subtypes including 24.5% of all am...
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Cell adhesion molecules play a central role in mediating axonal tract development within the nascent nervous system. NF-protocadherin (NFPC), a member of the non-clustered protocadherin family, has been shown to regulate retinal ganglion... more
Cell adhesion molecules play a central role in mediating axonal tract development within the nascent nervous system. NF-protocadherin (NFPC), a member of the non-clustered protocadherin family, has been shown to regulate retinal ganglion cell (RGC) axon and dendrite initiation, as well as influencing axonal navigation within the mid-optic tract. However, whether NFPC mediates RGC axonal behaviour at other positions within the optic pathway remains unclear. Here we report that NFPC plays an important role in RGC axonogenesis, but not in intraretinal guidance. Moreover, axons with reduced NFPC levels exhibit insensitivity to Netrin-1, an attractive guidance cue expressed at the optic nerve head. Netrin-1 induces rapid turnover of NFPC localized to RGC growth cones, suggesting that the regulation of NFPC protein levels may underlie Netrin-1-mediated entry of RGC axons into the optic nerve head. At the tectum, we further reveal a function for NFPC in controlling RGC axonal entry into th...
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The globular cluster system in M31 is an ideal laboratory for studying the formation and evolution of M31 as well as the globular clusters themselves. There have been numerous surveys and studies of the globular clusters in M31. However,... more
The globular cluster system in M31 is an ideal laboratory for studying the formation and evolution of M31 as well as the globular clusters themselves. There have been numerous surveys and studies of the globular clusters in M31. However, only recently has the entire body of M31 been searched for globular clusters using wide-field CCD images by our group. A new era for the M31 globular cluster system has begun with the advent of wide-field CCD surveys of M31. We have discovered more than 100 new globular clusters in M31. Our catalog currently includes more than 500 globular clusters confirmed either based on spectra or HST images, many more than in the Milky Way. We present the structure, kinematics and chemical abundance of the M31 globular cluster system based on this large sample, and the implications for the formation and evolution of M31.
We examined optokinetic and optomotor responses of 450 zebrafish mutants, which were isolated previously based on defects in organ formation, tissue patterning, pigmentation, axon guidance, or other visible phenotypes. These strains carry... more
We examined optokinetic and optomotor responses of 450 zebrafish mutants, which were isolated previously based on defects in organ formation, tissue patterning, pigmentation, axon guidance, or other visible phenotypes. These strains carry single point mutations in >400 essential loci. We asked which fraction of the mutants develop blindness or other types of impairments specific to the visual system. Twelve mutants failed to respond in either one or both of our assays. Subsequent histological and electroretinographic analysis revealed unique deficits at various stages of the visual pathway, including lens degeneration (bumper), melanin deficiency (sandy), lack of ganglion cells (lakritz), ipsilateral misrouting of axons (belladonna), optic-nerve disorganization (grumpy and sleepy), inner nuclear layer or outer plexiform layer malfunction (noir, dropje, and possibly steifftier), and disruption of retinotectal impulse activity (macho and blumenkohl). Surprisingly, mutants with abno...
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UK PubMed Central (UKPMC) is an archive of life sciences journal literature.
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MR. WILLIAM HARRIS (Luling, Louisiana): I think it is very appropriate to introduce a compliance chamber, in this case the Better BladderTM. With kinetic-assisted venous drainage using a centrifugal pump, there are two trains of thought.... more
MR. WILLIAM HARRIS (Luling, Louisiana): I think it is very appropriate to introduce a compliance chamber, in this case the Better BladderTM. With kinetic-assisted venous drainage using a centrifugal pump, there are two trains of thought. One is that we can use a centrifugal pump without any kind of compliance chamber, no matter what model of centrifugal pump is being used. The other train of thought, and I agree with this one, is a compliance chamber in a closed system with a centrifugal pump is probably a necessary addition. You have demonstrated really well in your study that you probably do dampen the high peak pressures and you also minimize gaseous microemboli (GME) by incorporating a compliance chamber. I think more studies have to be done before we can go ahead and just agree to that statement. Also, you had an arterial filter in your mini-system. The bubble counts were done distal to the arterial filter. Was air allowed to escape through a purge line attached to the filter before you did the measurements of GME?
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The oxidation of nickel powder under a controlled gas and temperature environment was studied using synchrotron-based full-field transmission X-ray microscopy. The use of this technique allowed for the reaction to be imaged in situ at 55... more
The oxidation of nickel powder under a controlled gas and temperature environment was studied using synchrotron-based full-field transmission X-ray microscopy. The use of this technique allowed for the reaction to be imaged in situ at 55 nm resolution. The setup was designed to fit in the limited working distance of the microscope and to provide the gas and temperature environments analogous to solid oxide fuel cell operating conditions. Chemical conversion from nickel to nickel oxide was confirmed using X-ray absorption near-edge structure. Using an unreacted core model, the reaction rate as a function of temperature and activation energy were calculated. This method can be applied to study many other chemical reactions requiring similar environmental conditions.
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Research Interests: Electrophysiology, Biology, Membrane Proteins, Immunohistochemistry, Medicine, and 15 moreBiological Sciences, Protein Structure and Function, Cercopithecus aethiops, Mice, Endocytosis, Animals, Immunoprecipitation, Rats, Membrane Protein, Axons, Rhodopsin, Protein Transport, Functional Properties, Cortical neurons, and Medical and Health Sciences
Symmetrically dividing neuroepithelial cells may produce two daughters that are both proliferating or both postmitotic, as highlighted by Zigman et al. in this issue of Neuron and Sanada and Tsai in a recent issue of Cell. Here, I will... more
Symmetrically dividing neuroepithelial cells may produce two daughters that are both proliferating or both postmitotic, as highlighted by Zigman et al. in this issue of Neuron and Sanada and Tsai in a recent issue of Cell. Here, I will attempt to offer a simple explanation why these results may be so different.
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Recent results are changing the way we think about cell-fate decision mechanisms in the retina. For a long time it was accepted that lineage was not important in retinal cellular determination but, as we review here, new data show that... more
Recent results are changing the way we think about cell-fate decision mechanisms in the retina. For a long time it was accepted that lineage was not important in retinal cellular determination but, as we review here, new data show that lineage programmes might be at the heart of this process. These programmes are intrinsic, but they are also plastic and are influenced by extrinsic signals.
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Cell determination in the retina has been under intense investigation since the discovery that retinal progenitors generate clones of apparently random composition (Price, J., D. Turner, and C. Cepko. 1987. Proc. Natl. Acad. Sci. USA.... more
Cell determination in the retina has been under intense investigation since the discovery that retinal progenitors generate clones of apparently random composition (Price, J., D. Turner, and C. Cepko. 1987. Proc. Natl. Acad. Sci. USA. 84:156–160; Holt, C.E., T.W. Bertsch, H.M. Ellis, and W.A. Harris. 1988. Neuron. 1:15–26; Wetts, R., and S.E. Fraser. 1988. Science. 239:1142–1145). Examination of fixed tissue, however, sheds little light on lineage patterns or on the relationship between the orientation of division and cell fate. In this study, three-dimensional time-lapse analyses were used to trace lineages of retinal progenitors expressing green fluorescent protein under the control of the ath5 promoter. Surprisingly, these cells divide just once along the circumferential axis to produce two postmitotic daughters, one of which becomes a retinal ganglion cell (RGC). Interestingly, when these same progenitors are transplanted into a mutant environment lacking RGCs, they often divide...
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Research Interests: Multidisciplinary, Macromolecular X-Ray Crystallography, HIV, Crystal structure, Ligand Binding, and 11 moreEnzyme, Human immunodeficiency virus, Active site, Pyridines, Protein Conformation, Reverse Transcriptase, Complex Structure, DNA binding proteins, Nevirapine, binding sites, and reverse transcriptase inhibitors
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Familial hyperalphalipoproteinemia (FHA) is a heritable trait associated with elevated plasma concentrations of high-density lipoprotein (HDL) cholesterol and possibly with longevity and protection against coronary heart disease (CHD).... more
Familial hyperalphalipoproteinemia (FHA) is a heritable trait associated with elevated plasma concentrations of high-density lipoprotein (HDL) cholesterol and possibly with longevity and protection against coronary heart disease (CHD). The metabolic basis and molecular etiology of FHA have not been established in most kindreds. The proband of a kindred with FHA and possible longevity was found to have elevated plasma levels of HDL cholesterol, apolipoprotein (apo) A-I, and lipoproteins containing apo A-I without apo A-II (Lp A-I), but normal levels of apo A-II and lipoproteins containing apo A-I with apo A-II (Lp A-I:A-II). The in vivo kinetics of apo A-I and apo A-II were studied in the FHA proband and in control subjects using both exogenous radiotracer (125I-apo A-I and 131I-apo A-II) and endogenous stable isotope (primed constant infusion of 13C6-phenylalanine) labeling techniques. The production rate (PR) of apo A-I was markedly increased in the FHA subject (28.9 mg/kg.d) compared with the control subjects (12.0 +/- 2.1 mg/kg.d), whereas the apo A-II PR was not substantially increased. The primary sequence of the proband&#39;s apo A-I gene, including 1.2 kb of the 5&#39;-flanking sequence, was normal. We conclude that a selective upregulation of apo A-I production is one metabolic cause of FHA, and results in high plasma concentrations of HDL cholesterol, apo A-I, and Lp A-I and possibly in protection from atherosclerotic CHD.
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Research Interests: Life Style, Medicine, CAD, Insulin Resistance, Humans, and 14 moreHypertension, Care, Mayo Clinic, Myocardial Revascularization, Myocardial Infarction, Oral Hypoglycemic Agents, Prognosis, Cardiovascular Diseases, Type 2 Diabetes Mellitus, HDL, Mayo Clinic Proceedings, Antihypertensive agents, Medical and Health Sciences, and Hyperlipidemias
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Debonding of the cement-metal interface of a cemented femoral component is one mechanism associated with loosening of total hip replacement. An ultrasonic pulse-echo technique was developed to determine, nondestructively, the integrity of... more
Debonding of the cement-metal interface of a cemented femoral component is one mechanism associated with loosening of total hip replacement. An ultrasonic pulse-echo technique was developed to determine, nondestructively, the integrity of the cement-metal interface in vitro. The characteristics of the ultrasonic reflections of bonded and debonded interfaces were obtained by using a physical model that consisted of a flat slab of cement and a flat cobalt alloy plate with known conditions of bonded and debonded interfaces. The same model was used to establish that the ultrasonic technique could distinguish between two surfaces that were in direct opposition but not bonded and those that were actually bonded. This technique then was shown to be useful in nondestructively detecting bonded and debonded cement-metal interfaces of femoral prostheses cemented into fiberglass femurs and femurs from human cadavera.
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The clinical presentation of a monoarticular, red, hot, and swollen joint has many possible diagnoses, including septic arthritis, which is 1 of the most devastating. The morbidity associated with this pathologic process involves... more
The clinical presentation of a monoarticular, red, hot, and swollen joint has many possible diagnoses, including septic arthritis, which is 1 of the most devastating. The morbidity associated with this pathologic process involves permanent joint damage and the potential for progression to systemic illness and, even, mortality. The common risk factors for joint sepsis include a history of rheumatoid arthritis, previous joint surgery, joint prosthesis, intravenous drug abuse, alcoholism, diabetes, previous intra-articular steroid use, and cutaneous ulceration. The diagnosis is primarily determined from the culture results after arthrocentesis and correlation with direct visualization, imaging, and various serologies, including synovial analysis. In the present report, a case of an insidious presentation of subtalar joint septic arthritis and its association with a unique patient presentation concomitant with primary immunodeficiency and culture-proven Myocplasma hominis infection is discussed. Septic arthritis has a predilection for the lower extremities and typically is isolated to the hip or knee, with less common involvement of the ankle or metatarsophalangeal joints. Owing to the uncommon nature of primary immunodeficiency disorders and the paucity of studies discussing their association with septic arthridites, we aimed to raise awareness of subtalar joint septic arthritis and to provide a brief overview of the pathogenesis as it presented in a 33-year-old male with X-linked hypogammaglobulinemia/agammaglobulinema.
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A diet low in saturated fat and cholesterol is the standard initial treatment for hypercholesterolemia. However, little quantitative information is available about the efficacy of dietary therapy in clinical practice or about the combined... more
A diet low in saturated fat and cholesterol is the standard initial treatment for hypercholesterolemia. However, little quantitative information is available about the efficacy of dietary therapy in clinical practice or about the combined effects of diet and drug therapy. One hundred eleven outpatients with moderate hypercholesterolemia were treated at five lipid clinics with the National Cholesterol Education Program Step 2 diet (which is low in fat and cholesterol) and lovastatin (20 mg once daily), both alone and together. A diet high in fat and cholesterol and a placebo identical in appearance to the lovastatin were used as the respective controls. Each of the 97 patients completing the study (58 men and 39 women) underwent four consecutive nine-week periods of treatment according to a randomized, balanced design: a high-fat diet-placebo period, a low-fat diet-placebo period, a high-fat diet-lovastatin period, and a low-fat diet-lovastatin period. The level of low-density lipoprotein (LDL) cholesterol was a mean of 5 percent (95 percent confidence interval, 3 to 7 percent) lower during the low-fat diet than during the high-fat diet (P &lt; 0.001). With lovastatin therapy as compared with placebo, the reduction was 27 percent. Together, the low-fat diet and lovastatin led to a mean reduction of 32 percent in the level of LDL cholesterol. The level of high-density lipoprotein (HDL) cholesterol fell by 6 percent (95 percent confidence interval, 4 to 8 percent) during the low-fat diet (P &lt; 0.001) and rose by 4 percent during treatment with lovastatin (P &lt; 0.001). The ratio of LDL to HDL cholesterol and the level of total triglycerides were reduced by lovastatin (P &lt; 0.001), but not by the low-fat diet. The effects of the low-fat-low-cholesterol diet and lovastatin on lipoprotein levels were independent and additive. However, the reduction in LDL cholesterol produced by the diet was small, and its benefit was possibly offset by the accompanying reduction in the level of HDL cholesterol.
Research Interests: England, Apolipoproteins, Humans, Cholesterol, Female, and 11 moreMale, Hypercholesterolemia, Triglycerides, Middle Aged, Cardiopulmonary Rehabilitation, Lovastatin, New England Journalof Medicine, Dietary fats, Combined Modality Therapy, Medical and Health Sciences, and Cardiovascular medicine and haematology
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The fatigue properties of Simplex P and Palacos R bone cements were compared to their antibiotic impregnated counterparts AKZ* and Palacos R with gentamycin. The effect of porosity reduction by centrifugation of all four cement types was... more
The fatigue properties of Simplex P and Palacos R bone cements were compared to their antibiotic impregnated counterparts AKZ* and Palacos R with gentamycin. The effect of porosity reduction by centrifugation of all four cement types was also assessed. Fifteen specimens of each cement type were prepared according to manufacturer&#39;s instructions and 15 additional specimens of each cement type were prepared by mixing the powder with chilled monomer (0 degrees C) and then centrifuging the cement immediately after mixing. Fifteen fully reversed tension-compression fatigue tests were performed at 15 MPa in stress control for each cement preparation in vitro while simulating the in vivo state (37 degrees C and 100% humidity). The number of cycles to failure were recorded. There was no significant difference in the fatigue life of Palacos R and Simplex P when both cements were prepared in the standard fashion. The addition of 1/2 g of gentamycin to Palacos R did not significantly alter its fatigue properties. The addition of 0.5 g of erythromycin and 0.24 g of colistin did not decrease the fatigue life of Simplex P. Centrifugation significantly improved the fatigue properties of Simplex P and AKZ. The fatigue lives of Palacos R and Palacos R with gentamycin were not improved by centrifugation. The fatigue life of centrifuged Simplex P was significantly greater than the fatigue life of Palacos R and of Palacos R with gentamycin, whether the Palacos R based cements were centrifuged or not.
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... Authors: Bragdon CR; O&#x27;Connor DO; Muratoglu OK; Ramamurti B.; Jasty M.; Lowenstein JD; Harris WH. ... The wear behavior of these three materials was compared to conventional UHMWPE using the AMTI Boston hip... more
... Authors: Bragdon CR; O&#x27;Connor DO; Muratoglu OK; Ramamurti B.; Jasty M.; Lowenstein JD; Harris WH. ... The wear behavior of these three materials was compared to conventional UHMWPE using the AMTI Boston hip simulator.METHODS:UHMWPE ram extruded bar stock (GUR ...
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Increasing cross-linking has been shown in vitro and in vivo to improve markedly the wear resistance of ultra-high-molecular-weight polyethylene (UHMWPE). The reduction in the mechanical properties of polyethylene under certain methods... more
Increasing cross-linking has been shown in vitro and in vivo to improve markedly the wear resistance of ultra-high-molecular-weight polyethylene (UHMWPE). The reduction in the mechanical properties of polyethylene under certain methods used to produce cross-linking has been a concern, however. These reductions are known to result from the processes used to increase the cross-link density and could affect the device performance in vivo. We present a novel method of increasing the cross-link density of UHMWPE in which UHMWPE is irradiated in air at an elevated temperature with a high-dose-rate electron beam and subsequently is melt-annealed. This treatment improves markedly the wear resistance of the polymer as tested in a hip simulator, while maintaining the mechanical properties of the material within national and international standards. This method leads to the absence of detectable free radicals in the polymer and, as a result, excellent resistance to oxidation of the polymer.
Research Interests: Biomedical Engineering, Free Radicals, Wear, Medicine, Free Radical, and 15 moreHumans, Computer Simulation, The, Polyethylene, Arthroplasty, Clinical Sciences, Surface Properties, prosthesis Design, Materials Testing, Polyethylenes, Electron Beam, Biocompatible Materials, Elevated Temperature, Mechanical Property, and High Molecular Weight
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In this study, we compare the in vivo wear performance of electron beam-irradiated, postirradiation-melted, highly cross-linked polyethylene (HXLPE) and traditional UHMWPE via the Martell method. Seventy hips with HXLPE performed at the... more
In this study, we compare the in vivo wear performance of electron beam-irradiated, postirradiation-melted, highly cross-linked polyethylene (HXLPE) and traditional UHMWPE via the Martell method. Seventy hips with HXLPE performed at the Massachusetts General Hospital had 138 radiograph pairs for wear analysis and a 31.2-month average follow-up (range, 24-44 months). An age-matched, sex-matched, and body mass index-matched subgroup of 111 hips with 214 acceptable radiograph pairs and a 4-year follow-up from our previously published study on traditional polyethylene performed at Rush-Presbyterian-St. Luke&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Medical Center served as a control group. Martell wear analysis was performed for each group. Overall and steady-state wear rates were compared via a specialized t test. The steady-state wear in the HXLPE arm was observed after 2.0 years, was 0.007 mm/y, and was significantly less than the steady-state wear in the traditional arm (0.174 mm/y) (P = .003). Highly cross-linked polyethylene penetration rate was not affected by sex, age, activity, or body mass index by Mann-Whitney analysis.
Research Interests: Biomedical Engineering, Medicine, Humans, Female, Male, and 15 moreThe, Polyethylene, Body Mass Index, Arthroplasty, Steady state, Clinical Sciences, Middle Aged, Body Mass, prosthesis Design, Materials Testing, Electron Beam, Massachusetts General Hospital, Electron beam irradiation, Control Group, and Total hip arthroplasty
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Progressive muscle relaxation (PMR) is a broadly useful anxiety reduction technique that has been found to lower blood pressure (BP) in essential hypertension. The present investigation is the first to evaluate the feasibility and... more
Progressive muscle relaxation (PMR) is a broadly useful anxiety reduction technique that has been found to lower blood pressure (BP) in essential hypertension. The present investigation is the first to evaluate the feasibility and efficacy of wide-scale PMR instruction as a public health promotion strategy aimed at adolescents. Students (N = 1,400) in Grades 9 and 10 at two large Baltimore City public high schools underwent BP screening; those with BP persistently above the 85th percentile were randomly assigned to (a) 12 weeks daily PMR instruction provided in class for academic credit or (b) a control condition. The latter students had their BP measured at the same frequency as the PMR students and completed the PMR course during the following year. Approximately two thirds of eligible students entered and completed the study. Results demonstrated that treatment students (n = 51) enjoyed daily PMR, mastered the technique, and achieved reduced systolic BP at posttest relative to the untrained controls (n = 59). At follow-up 4 months later, group BP differences were not significant. Implications for use of PMR to promote cardiovascular health are discussed.
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Hedgehog signaling has been linked to cell proliferation in a variety of systems; however, its effects on the cell cycle have not been closely studied. In the vertebrate retina, Hedgehog's effects are controversial, with some reports... more
Hedgehog signaling has been linked to cell proliferation in a variety of systems; however, its effects on the cell cycle have not been closely studied. In the vertebrate retina, Hedgehog's effects are controversial, with some reports emphasizing increased proliferation and others pointing to a role in cell cycle exit. Here we demonstrate a novel role for Hedgehog signaling in speeding up the cell cycle in the developing retina by reducing the length of G1 and G2 phases. These fast cycling cells tend to exit the cell cycle early. Conversely, retinal progenitors with blocked Hedgehog signaling cycle more slowly, with longer G1 and G2 phases, and remain in the cell cycle longer. Hedgehog may modulate cell cycle kinetics through activation of the key cell cycle activators cyclin D1, cyclin A2, cyclin B1, and cdc25C. These findings support a role for Hedgehog in regulating the conversion from slow cycling stem cells to fast cycling transient amplifying progenitors that are closer to ...
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From a group of 43 hips in 41 patients, previously reported at an average of six years of follow-up evaluation, in whom second-generation cementing techniques were used during femoral revision hip surgery, 38 hips in 36 patients were... more
From a group of 43 hips in 41 patients, previously reported at an average of six years of follow-up evaluation, in whom second-generation cementing techniques were used during femoral revision hip surgery, 38 hips in 36 patients were rereviewed at an average follow-up period of 11.7 years (range, 118-172 months). The average age of the patients at the time of revision surgery was 52.8 years. Only four femoral components (10.5%) required rerevision for aseptic loosening. Of those not rerevised, the average Harris hip score at the time of follow-up evaluation was 81. Four additional hips (10.5%) had radiographic evidence of definite femoral component loosening. The survival of 90% of the implants of cemented femoral revision surgery and the 79% incidence of well-fixed femoral components for more than 11.7 years is attributed to the improved cementing techniques and modern stem design.
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Loosening of total joint prostheses is in part related to the fragmentation of the acrylic cement mantle surrounding the prosthesis and the biologic consequences to the particulate acrylic. Fractographic studies of femoral cement mantles... more
Loosening of total joint prostheses is in part related to the fragmentation of the acrylic cement mantle surrounding the prosthesis and the biologic consequences to the particulate acrylic. Fractographic studies of femoral cement mantles retrieved at revision surgery and autopsy showed frequent fractures in varying stages of development in the cement and wear at the fracture surfaces. Defects in the cement mantle, thin mantles, sharp corners on the prosthesis, separation at the cement mantle interface, and pores in the cement were frequently associated with cement fractures. The progressive fractures and wear led to the liberation of particulate acrylic debris into the surrounding tissues. The tissues at the bone-cement interface removed at revision surgery showed that a macrophage, giant-cell foreign-body granulomatous reaction occurs in response to the particulate, but not bulk cement. This tissue can produce a variety of chemical mediators of inflammation and bone resorption, and can resorb bone in organ cultures. A granulomatous tissue reaction with a very similar appearance can be produced in experimental animals using particulate-form polymethylmethacrylate (PMMA), but not the bulk form of PMMA. The tissue reaction is not mediated by the classic cell or humeral immune mechanisms. Subcutaneous injection of particulate PMMA powder into fully immunocompetent C3Hf/SED mice as well as three strains of mice with progressive immunologic deficiencies (nude/nude, SCID, and triple deficient Nu-bg-XID/SED mice) led to a foreign-body reaction in all strains at five weeks as shown by histologic and immunohistochemical examination despite the differences in immune deficiency. This, along with the scarcity of lymphocytes in the human tissues, suggests that the biologic reactions to fragmented cement can be produced and sustained by nonimmune phagocytosis and activation by macrophages and giant cells without significant contribution by the immune system.
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Aseptic loosening is the most common long-term complication of cemented total hip arthroplasties (THA). The functional longevity of these implants depends on the bone-cement interface. The influence of cement injection pressure, type of... more
Aseptic loosening is the most common long-term complication of cemented total hip arthroplasties (THA). The functional longevity of these implants depends on the bone-cement interface. The influence of cement injection pressure, type of cement, ambient temperature, chilling of the monomer, and centrifugation of cement-on-cement intrusion depth was investigated in specimens of bovine cancellous bone. In order to validate the bovine model for comparative purposes relative to use in man, a linear relationship between human and bovine cancellous bone was first demonstrated for various porosities and cement intrusion depth. Three cements (Low Viscosity Cement [LVC], Simplex-P, and Palacos) were intruded at three different pressures (20, 40, and 60 PSI) at the same ambient temperature and relative humidity into commercially prepared plugs of bovine cancellous bone. Cement intrusion depth was proportional to injection pressure for all three cements, but was significantly different for each cement at a given pressure. At 20, 40, and 60 PSI, Palacos had a cement intrusion depth of 1.4, 2.4, and 2.8 mm respectively, while the figures for Simplex-P were 2.2, 4.2, and 5.0 mm, and for LVC were 8.0, 12.0, and 14.6 mm. Ambient temperature had an inverse relationship with cement intrusion depth for all three cements given the same experimental conditions. Chilling the monomer increased the intrusion of Simplex-P to 5.8, 8.2, and 12.7 mm at 20, 40, and 60 PSI injection pressure respectively. Simplex-P intrusion depth was not modified by cement centrifugation at any of the three injection pressures tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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A detailed biomechanical, histologic, and histomorphometric analysis of autopsy specimens from patients who previously had cemented total hip arthroplasty has helped to elucidate the skeletal response to cemented components. Bone cement... more
A detailed biomechanical, histologic, and histomorphometric analysis of autopsy specimens from patients who previously had cemented total hip arthroplasty has helped to elucidate the skeletal response to cemented components. Bone cement has the capacity to provide long-term implant stability. The biologic response to polyethylene wear debris has a more critical effect on destabilization of cemented sockets compared with the femoral side. In contrast, mechanical events tended to predominate the early mode of destabilization of cemented femoral components with debonding at the metal-cement interface and fracture in the cement. Fractures predominate in cement mantles less than 1 mm thick and are associated with mantle defects, debonded interfaces, and sharp corners of the implants. Correlation of the histologic findings at the cement-bone interface with radiolucencies seen on clinical radiographs show that on the acetabular side radiolucencies represent a soft tissue membrane that is the biologic response to polyethylene debris. In contrast, on the femoral side, most radiolucencies were as a result of skeletal remodeling. Femoral adaptive bone remodeling is a diffuse process that occurs over the entire fixation surface. The most profound disuse osteoporosis occurred proximally in the proximal medial quadrant; however, when one takes into account all four quadrants, anterior, posterior, medial, and lateral, the most severe osteoporosis occurred at the midpoint of the stem.