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At least 181 records · Page 10Linked to original sources

High-turnover periprosthetic bone remodeling and immature bone formation around loose cemented total hip joints.

Aseptic loosening and periprosthetic osteolysis are the major problems awaiting solution in total hip surgery. The clinical investigation focused on the analysis of periprosthetic bone remodeling to clarify one important key event in the cascade of periprosthetic connective tissue weakening and osteolysis around loose artificial hip joints. Twelve acetabular bone samples adjacent to granulomatous synovial-like membrane of loose hip prosthesis were retrieved at revision surgery and processed for Villanueva bone staining for morphological observation and bone histomorphometric analysis. Eight well-fixed bony samples were used as control. Although osteoclastic surface and eroded surface by osteoclasts were evident in the periprosthetic bone from loose hip joints (p = 0.003 and p = 0.027), increased osteoid/low-mineralized bone matrix (p < 0.001) and osteoid width (p < 0.001) also were significant findings in structural analysis. In addition, not only elevated mineral apposition rate (MAR; p = 0.044) but also increased mineralizing surface (p = 0.044) and bone formation rate (BFR; p = 0.002) in loose periprosthetic bones were shown in dynamic data analysis. These results were confirmed by precise morphological observation by confocal laser scanning microscopy. Active coupling of bone formation and resorption and increased osteocytes with abundant bone canalicular projections were found in combined with the presence of immature bone matrices (osteoid and low-mineralized bone areas) in periprosthetic bones from loose hip joints. These results indicated that active osteoclastic bone resorption and/or defective bone formation are coupled with monocyte/macrophage-mediated foreign body-type granuloma in the synovial-like interface membrane of loose hip joints. Thus, this unique high-turnover periprosthetic bone remodeling with bad bone quality probably is caused by the result of cellular host response combined with inappropriate cyclic mechanical loading. The fragile periprosthetic bone may contribute to hip prosthesis loosening.

Aged↗

Histologic evaluation of a 9-year-old hydroxyapatite-coated cylindric implant placed in conjunction with a subantral augmentation procedure: a case report.

The histologic examination of dental implants retrieved from humans provides a unique opportunity to evaluate the bone-implant interface. This case report presents a clinical, radiographic, and histologic evaluation of a cylindrical hydroxyapatite- (HA) coated implant retrieved from the posterior maxillary area of a patient after 9 years after placement. The implant had been placed in conjunction with a subantral augmentation procedure with HA as the graft material. Clinical examination revealed an immobile implant with no sign of pathosis. Radiographic examination indicated close proximity of the bone to the implant surface without evidence of radiolucency. Histologically, because of tissue destruction during implant retrieval, only the apical portion of the implant was available for examination under light microscopy, and it appeared to be integrated with the surrounding bone; 45.9% of the surface of the implant had close bone apposition at the interface. There was no evidence of dissolution of the HA coating and the bone appeared to be in immediate contact with the coating. Residual graft particles were present and in close proximity with the implant surface. These observations suggest that the subantral augmentation procedure performed simultaneously with the placement of an HA-coated implant with HA as the graft material apparently resulted in osseointegration between the implant and the surrounding bone. The implant was maintained without complication for 9 years.

Alveolar Ridge Augmentation↗

Ultrasonic diagnosis of renal and retroperitoneal lesions.

The unique ability of ultrasound to detect soft tissue interfaces makes it a prime tool for at least one major diagnostic approach to soft tissue lesions. Systematic ultrasonic examination of suspected masses in the abdomen should be performed early in the course of investigation. It will help direct additional studies and often result in cost savings by making the diagnostic process more efficient. The method is painless, to the best of our knowledge harmless and can be repeated at will for early study or late follow-up. The ultrasonic look into the body has provided us with a major tool for obtaining far more information on internal structures than was possible even a few years ago. Ultrasonic scans, radioisotope examinations and computerized x-ray tomography are leading us into an era of much increased anatomic knowledge about lesions which heretofore were obscure and difficult to evaluate.

Abdominal Neoplasms↗

Digital approaches to myoelectric state control of prostheses.

The design of a new three-state myoelectric control system is presented. This controller determines its operating state from the initial rate of increase of the myoelectric signal, and the concept is realized in great measure through digital logic techniques. Proportional control of both active states (same dynamic range) is a unique feature of the controller. A microcomputer was interfaced in a simple way with myoelectric potentials to simulate the three-state controller described and to simulate various other state-determined control methods (some multifunctional). This was found to be a valuable method of evaluating control schemes without building the actual devices.

Adult↗

Localization of agonist and competitive antagonist binding sites on nicotinic acetylcholine receptors.

Identification of all residues involved in the recognition and binding of cholinergic ligands (e.g. agonists, competitive antagonists, and noncompetitive agonists) is a primary objective to understand which structural components are related to the physiological function of the nicotinic acetylcholine receptor (AChR). The picture for the localization of the agonist/competitive antagonist binding sites is now clearer in the light of newer and better experimental evidence. These sites are located mainly on both alpha subunits in a pocket approximately 30-35 A above the surface membrane. Since both alpha subunits are identical, the observed high and low affinity for different ligands on the receptor is conditioned by the interaction of the alpha subunit with other non-alpha subunits. This molecular interaction takes place at the interface formed by the different subunits. For example, the high-affinity acetylcholine (ACh) binding site of the muscle-type AChR is located on the alphadelta subunit interface, whereas the low-affinity ACh binding site is located on the alphagamma subunit interface. Regarding homomeric AChRs (e.g. alpha7, alpha8, and alpha9), up to five binding sites may be located on the alphaalpha subunit interfaces. From the point of view of subunit arrangement, the gamma subunit is in between both alpha subunits and the delta subunit follows the alpha aligned in a clockwise manner from the gamma. Although some competitive antagonists such as lophotoxin and alpha-bungarotoxin bind to the same high- and low-affinity sites as ACh, other cholinergic drugs may bind with opposite specificity. For instance, the location of the high- and the low-affinity binding site for curare-related drugs as well as for agonists such as the alkaloid nicotine and the potent analgesic epibatidine (only when the AChR is in the desensitized state) is determined by the alphagamma and the alphadelta subunit interface, respectively. The case of alpha-conotoxins (alpha-CoTxs) is unique since each alpha-CoTx from different species is recognized by a specific AChR type. In addition, the specificity of alpha-CoTxs for each subunit interface is species-dependent. In general terms we may state that both alpha subunits carry the principal component for the agonist/competitive antagonist binding sites, whereas the non-alpha subunits bear the complementary component. Concerning homomeric AChRs, both the principal and the complementary component exist on the alpha subunit. The principal component on the muscle-type AChR involves three loops-forming binding domains (loops A-C). Loop A (from mouse sequence) is mainly formed by residue Y(93), loop B is molded by amino acids W(149), Y(152), and probably G(153), while loop C is shaped by residues Y(190), C(192), C(193), and Y(198). The complementary component corresponding to each non-alpha subunit probably contributes with at least four loops. More specifically, the loops at the gamma subunit are: loop D which is formed by residue K(34), loop E that is designed by W(55) and E(57), loop F which is built by a stretch of amino acids comprising L(109), S(111), C(115), I(116), and Y(117), and finally loop G that is shaped by F(172) and by the negatively-charged amino acids D(174) and E(183). The complementary component on the delta subunit, which corresponds to the high-affinity ACh binding site, is formed by homologous loops. Regarding alpha-neurotoxins, several snake and alpha-CoTxs bear specific residues that are energetically coupled with their corresponding pairs on the AChR binding site. The principal component for snake alpha-neurotoxins is located on the residue sequence alpha1W(184)-D(200), which includes loop C. In addition, amino acid sequence 55-74 from the alpha1 subunit (which includes loop E), and residues gammaL(119) (close to loop F) and gammaE(176) (close to loop G) at the low-affinity binding site, or deltaL(121) (close to the homologous region of loop G) at the high-affinity binding site, are i

Animals↗

Cellular electrophysiology of coronary artery ligation in chronic pressure overload.

We evaluated ischemia-induced cellular electrophysiologic abnormalities in chronic pressure overload ventricular myocardium in vitro. Left ventricular systolic hypertension was induced in cats via partial supracoronary aortic constriction (overload); at 1 1/2-3 months, resulting pressure overload was accompanied by ventricular hypertrophy (25-35% by weight) and patchy endocardial fibrosis. Two hours of subsequent acute myocardial ischemia (ischemia) was imposed on overload (ischemia/overload) via total occlusion of distal branches of the left coronary artery system. Spontaneous premature depolarizations in vitro were increased in ischemia/overload compared to control, ischemia or overload alone; bursts of spontaneous, repetitive depolarizations were also unique to these preparations. Multiple site recordings of endocardial transmembrane action potentials overlying the borders (interface) of fibrotic areas in ischemia/overload demonstrated numerous electrophysiologic abnormalities, including several not observed in control, ischemia or overload. Unique to the border areas of ischemia/overload preparations was the presence of maintained but depressed resting potential without action potentials; also, the incidence of depolarizations at the onset of the plateau phase was highest in these preparations. In non-fibrotic areas, electrophysiologic properties including resting potential and action potential amplitude and rate of rise were diminished in ischemia/overload compared to ischemia or overload preparations. These data demonstrate that acute myocardial ischemia in the setting of chronic pressure overload leads to additional cellular electrophysiologic abnormalities compared to ischemia or overload alone.

Action Potentials↗

A new adhesive bonding material for the cementation of implantable devices in otologic surgery.

BACKGROUND: Presently, there are no U.S. Food and Drug Administration (FDA)-approved adhesive bone cements for the surgical fixation of prosthetic materials in the middle ear. A promising new cement, 4-META/MMA-TBB opaque resin, has shown remarkable adhesive properties as a bone cement in vivo. The cement is composed of 4-methacryloyloxyethyl trimellitate anhydride (4-META) and methyl methacrylate (MMA) as monomers and tri-n-butyl borane (TBB) as an initiator. METHODS: An electromagnetic semiimplantable hearing device presently under development was implanted into the middle ear of six cats using 4-META/MMA-TBB resin to cement a titanium-encased magnet to the incus. The animals were subsequently killed (at a mean of 9.6 months) to assess the (temporal bones and specifically the magnet-incus complex in each animal. RESULTS: The titanium-encapsulated magnet was firmly adherent to all incuses without any failure of the cement-bone interface. Histopathologic examination of the implanted temporal bones demonstrated lack of middle ear inflammation. Transmission electron microscopy of the incuses demonstrated a unique "hybrid layer" in the bone-side subsurface of the bone-cement interface that elucidates the mechanism of interfacial adhesion. CONCLUSIONS: Our investigation highlights the special biomechanical properties as well as the biocompatibility of 4-META/ MMA-TBB resin that make it an attractive bone-bonding agent for use in otologic surgery, including its potential usefulness during ossicular reconstruction.

Animals↗

A protocol for maintaining multidatabase referential integrity.

The bioinformatics community is becoming increasingly reliant on the creation of links among biological databases (DBs) as a foundation for DB interoperability. For example, a link might be created from a protein in one DB (such as PIR), to a gene in another DB (such as GDB), by storing the unique identifier (id) of the gene object within an attribute of the protein object. User interfaces can then support navigation from the protein to the gene, and multiDB queries can join the protein with the gene. The unique id of the gene is serving as a foreign key. However, a variety of factors, such as changes in the underlying biology, can cause object ids to become invalid, thus producing invalid links among DBs. Invalid links are a violation of multidatabase referential integrity. We propose a network protocol whereby a database administrator can provide information about changes to the identifiers of objects in their database via Internet, to allow other databases to maintain referential integrity. We request comments from the bioinformatics community for the purpose of building a consensus on the proposed protocol.

Computational Biology↗

Tumor-associated antigens recognized by human monoclonal antibodies.

BACKGROUND: Nonhuman monoclonal antibodies (MoAbs) of desired specificities have been studied in cancer treatment and tumor targeting with minimal success. Attempts of using humanized chimeric antibodies have not improved significantly their clinical applications. We have engaged in the development of human MoAbs by incorporating the in vitro immunization protocols to the nodal lymphocytes of cancer patients. Three human MoAbs thus generated were found to be strongly reactive with various human malignancies. The antigens recognized by the three antibodies were selected for immunochemical and biochemical characterizations. METHODS: The antigens investigated were AgSK1, PA 1-2 and PA 3-1. The patterns of each antigen expression in various human cancer cell lines were studied by the immunocytochemical staining technique. The expression of AgSK1 in association with cellular proliferation was examined by the flow cytometry analysis. In studying the biochemical natures of these antigens, their sensitivities toward various chemical and physical treatments were determined. The antigens that were shown to be proteins were subjected to SDS-PAGE and Western blot for estimations of molecular weights. RESULTS: The AgSK1 was detected in 10 human carcinoma cell lines but in none of the melanoma cell lines. This suggests that SK1 may be an epithelial or carcinoma marker. The phenotypic expressions of AgSK1 were shown to be associated with proliferation of carcinoma cells. Biochemically AgSK1 was a sialophycoprotein with an estimated molecular weight of 42-44 kilodaltons (kDa). HuMAb PA1-2 demonstrated a unique staining pattern at both the cytoplasmic and intercellular interface. The stained filamentlike structures extending from cell to cell indicated that Ag PA1-2 might play a role in cellular interactions. Biochemically, Ag PA1-2 appeared to be an asialocarbohydrate. The Ag PA3-1 was a cytoplasmic glycoprotein expressed by all 13 cell lines. The estimated molecular weights of PA3-1 were 164, 104, and 40 kDa. CONCLUSIONS: Tumor-associated antigens recognized by the human MoAbs may be more relevant clinically than those recognized by the mouse immune system. Carcinoma-specific human MoAbs are desirable for cancer treatment and tumor localization.

Antibodies, Monoclonal↗

An improved accuracy six-load component pedal dynamometer for cycling.

This paper describes a new six-load component pedal dynamometer designed for study of knee overuse injury in cycling. A unique capability of the dynamometer is the ability to interface with multiple pedal platforms of varying height while maintaining a desired elevation of the foot above the pedal spindle axis. The dynamometer was designed using a concept described in an earlier article by Quinn and Mote (1991, Exp. Mech. 30, 40-48) which measures shear strain across multiple, thin cross-sections. An optimal design technique was used for choosing dimensions of the load measuring cross-sections. A dynamometer was designed and built using the optimal results. Calibration, accuracy results, and sample data are presented. A comparison of accuracy reveals that the new dynamometer is more accurate than previously reported instruments.

Bicycling↗

The skin immune system: progress in cutaneous biology.

The skin is an active, and in many ways unique, immunological microenvironment quite different from the other primary interfaces between the body and the environment (namely the mucosae). Here Jan D. Bos and Martien L. Kapsenberg identify the components of the skin immune system and describe the inflammatory and immunological responses that they can mount. New findings with regard to the immunophysiology and physiopathology of the human integument are emphasized.

Autoimmune Diseases↗

Nonradioactive in situ hybridization for detection of hydrophobin mRNA in the phytopathogenic fungus Claviceps purpurea during infection of rye.

Hydrophobins are unique fungal extracellular proteins that produce amphipathic films at interfaces, mediate contact to hydrophobic surfaces and are known to be important in phytopathogenicity. In the pathogenic ascomycete Claviceps purpurea, causing ergot disease in grasses and cereals and ergotism in livestock, a gene encoding an extraordinary type of hydrophobin has been detected, which appeared to be induced during alkaloid synthesis in axenic culture of an ergot-alkaloid producing strain of Claviceps (V. Garre and P. Tudzynski, pers. communication; Arntz and Tudzynski, 1997, Curr. Genet. 31, 357-360). To elucidate presence and function of this hydrophobin during infection of rye, the nonradioactive in situ hybridization technique was successfully adapted to the fungal organism and optimized in the pathogenic interaction system. Semithin cryosections proved to be suitable for microscopical gene expression analysis using immune-mediated alkaline-phosphatase staining for detection of digoxigenin-labeled cRNA probes. Specific hybridization of the prepared antisense riboprobe to hydrophobin mRNA was confirmed in nonradioactive Northern blots. While permeabilization by proteinase K had only a minor effect, the inclusion of detergent into the hybridization solutions enhanced specific RNA-RNA hybridization under maximum stringency. Hydrophobin mRNA was found in fungal cells, growing in axenic culture. In the disease cycle, hydrophobin transcripts were localized in abundance during vegetative fructification in conidiophores that actively produced conidia. No signals were observed in sclerotial hyphae during formation of the alkaloid-containing ergots, although they fluoresced intensely during total RNA detection using acridine orange. Notably, in situ hybridization experiments resulted in specific signals during early infection and colonization phases in the external mycelia and in hyphae penetrating the host epidermal layer. The presumed role of the hydrophobin gene product in ergot pathogenicity is discussed with respect to the described spatio-temporal distribution of the hydrophobin transcripts.

Claviceps↗

Construction of a synthetic gene for the metalloregulatory protein MerR and analysis of regionally mutated proteins for transcriptional regulation.

The transcriptional control protein MerR is a metalloregulatory switch, activating transcription of a mercury resistance operon in the presence of mercuric ions and repressing transcription in their absence. We report here the construction and utilization of a synthetic merR gene and a single-copy merT'-lacZ fusion reporter for mutagenic analysis of the MerR protein's function. Site-directed mutagenesis of clustered acidic residues within the central region of the MerR protein indicated that these residues are important to the protein's ability to repress transcription. Quadruple or sextuple mutations involving residues E83 and E84 and other nearby acidic residues result in a repression-deficient (RD) phenotype. One of the mutant proteins was purified and shown by gel shift assay to retain binding to its operator DNA with an affinity similar to wild-type protein, suggesting that transcriptional repression does not correlate with MerR binding affinity. A small region of merR corresponding to residues 81-92 also was mutagenized in a search for other RD mutants and for mutants displaying sufficient transcriptional activation in the absence of mercuric ion to be classified as constitutive activation (CA) mutants. In this case, oligonucleotide-directed randomization of the target region and a screening/selection protocol were employed. Sixteen different mutants with an RD phenotype were identified, as well as eight different mutants with a CA phenotype. A high frequency of S87C mutations is evident in the RD set of mutants. The CA mutants have a high incidence of S86C and A89V mutations. The CA double mutant S86C/A89V was purified and found to bind to its DNA site with an affinity similar to that of the wild-type protein. Chemical nuclease activity assays indicate that the nonmercurated S86C/A89V CA mutant has a DNA distortion activity identical to that of mercurated wild-type MerR. A unique disulfide bond bridging this CA mutant's dimer interface was found and is proposed to constrain protein conformation in a manner analogous to mercuric ion binding in the wild-type protein.

Amino Acid Sequence↗

Free-thiol Cys331 exposed during activation process is critical for native tetramer structure of cathepsin C (dipeptidyl peptidase I).

The mature bovine cathepsin C (CC) molecule is composed of four identical monomers, each proteolytically processed into three chains. Five intrachain disulfides and three nonpaired cysteine residues per monomer were identified. Beside catalytic Cys234 in the active site, free-thiol Cys331 and Cys424 were characterized. Cys424 can be classified as inaccessible buried residue. Selective modification of Cys331 results in dissociation of native CC tetramer into dimers. The 3D homology-based model of the CC catalytic core suggests that Cys331 becomes exposed as the activation peptide is removed during procathepsin C activation. The model further shows that exposed Cys331 is surrounded by a surface hydrophobic cluster, unique to CC, forming a dimer-dimer interaction interface. Substrate/inhibitor recognition of the active site in the CC dimer differs significantly from that in the native tetramer. Taken together, a mechanism is proposed that assumes that the CC tetramer formation results in a site-specific occlusion of endopeptidase-like active site cleft of each CC monomeric unit. Thus, tetramerization provides for the structural basis of the dipeptidyl peptidase activity of CC through a substrate access-limiting mechanism different from those found in homologous monomeric exopeptidases cathepsin H and B. In conclusion, the mechanism of tetramer formation as well as specific posttranslational processing segregates CC in the family of papain proteases.

Amino Acid Sequence↗

Melatonin synthesis enzymes in Macaca mulatta: focus on arylalkylamine N-acetyltransferase (EC 2.3.1.87).

Arylalkylamine N-acetyltransferase (AANAT; serotonin N-acetyltransferase, EC 2.3.1.87) plays a unique transduction role in vertebrate physiology as the key interface between melatonin production and regulatory mechanisms. Circulating melatonin is elevated at night in all vertebrates, because AANAT activity increases in the pineal gland in response to signals from the circadian clock. Circadian regulation of melatonin synthesis is implicated in a variety of human problems, including jet lag, shift work, insomnia, and abnormal activity rhythms in blind persons. In this report AANAT was studied in the rhesus macaque to better understand human melatonin regulation. AANAT mRNA is abundant in the pineal gland and retina, but not elsewhere; AANAT mRNA is uniformly distributed in the pineal gland, but is limited primarily to the photoreceptor outer segments in the retina. Day and night levels of pineal and retinal AANAT mRNA are similar. In contrast, AANAT activity and protein increase more than 4-fold at night in both tissues. The activity of hydroxyindole-O-methyltransferase, the last enzyme in melatonin synthesis, is tonically high in the pineal gland, but is nearly undetectable in the retina; hydroxyindole O-methyltransferase mRNA levels exhibited a similar pattern. This supports the view that the source of circulating melatonin in primates is the pineal gland. The discovery in this study that rhesus pineal AANAT mRNA is high at all times is of special importance because it shows that posttranscriptional control of this enzyme plays a dominant role in regulating melatonin synthesis.

Acetylserotonin O-Methyltransferase↗

Osteopontin: an interfacial extracellular matrix protein in mineralized tissues.

Among the noncollagenous matrix proteins found in mineralized tissues (MTs), colloidal-gold immunocytochemistry has demonstrated that the ultrastructural distribution of osteopontin (OPN) is unique in that this protein preferentially accumulates at MT interfaces. In bone, OPN is present as a major component of cell- and matrix-matrix interfacial structures termed laminae limitantes and cement lines, respectively. Here, we review the implications of this distinct, interfacial tissue distribution as it relates to the properties and functional motifs of OPN (e.g. RGD, polyAsp, phosphorylation) in different MTs, and more specifically, how it pertains to current theory on the cellular and extracellular matrix (ECM) events associated with bone remodeling. The production of OPN as one of the earliest, and latest, secretory activities of the osteoblast lineage is discussed, together with a consideration of the role of OPN in cement lines and laminae limitantes in bone and in other normal, pathological and healing MTs such as teeth, kidney stones, bone wound healing and implant osseointegration. Further to its ability to influence cell dynamics, calcification and possibly tissue cohesion in MTs, it is proposed that OPN in cement lines may also promote adhesion between apposing substrata. With regard to this latter function, it is suggested that the molecular interactions within, and biomechanical properties of, such an OPN-rich interfacial zone may be important in minimizing strain-induced fatigue damage and microcrack propagation in bone and across other MT interfaces.

Animals↗

DICOM versus HL7 for modality interfacing.

Digital modalities such as CT, MRI, Ultrasound and Computerized Radiography systems, generating softcopy images to be used by a Picture Archiving and Communication System (PACS), need to identify the images properly in order to retrieve and manage them. In many cases, a technologist re-enters patient demographic and study related information at the modality, even although it is usually already present somewhere in the hospital information system (IS). In order to achieve a higher level of efficiency and uniquely identify the created image objects, it is obvious that an interface between the IS and modality to exchange this information is highly desired. There are two options for a modality vendor to implement an IS interface, either using the Health Level (HL7) or Digital Imaging Communication in Medicine (DICOM) communication standard. This paper will explain characteristics of both protocols, and demonstrate that it is preferred to use DICOM versus HL7. In addition, it will show that DICOM is supported by most modality vendors, based on the result of a poll of their Modality Worklist versus HL7 support.

Diagnostic Imaging↗

Stabilizing the open conformation of the integrin headpiece with a glycan wedge increases affinity for ligand.

The affinity of the extracellular domain of integrins for ligand is regulated by conformational changes signaled from the cytoplasm. Alternative types of conformational movement in the ligand-binding headpiece have been proposed. In one study, electron micrograph image averages of the headpiece of integrin aV beta 3 show two different conformations. The open conformation of the headpiece is present when a ligand mimetic peptide is bound and differs from the closed conformation in the presence of an obtuse angle between the beta 3 subunit hybrid and I-like domains. We tested the hypothesis that opening of the hybrid-I-like domain interface increases ligand-binding affinity by mutationally introducing an N-glycosylation site into it. Both beta 3 and beta1 integrin glycan wedge mutants exhibit constitutively high affinity for physiological ligands. The data uniquely support one model of integrin activation and suggest that movement at the interface with the hybrid domain pulls down the C-terminal helix of the I-like domain and activates its metal ion-dependent adhesion site, analogously to activation of the integrin I domain.

Animals↗