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Toru Shimizu

Publications and source records attributed to Toru Shimizu.

At least 37 records · Page 2Linked to original sources
PubMed2004

Revised nomenclature for avian telencephalon and some related brainstem nuclei.

The standard nomenclature that has been used for many telencephalic and related brainstem structures in birds is based on flawed assumptions of homology to mammals. In particular, the outdated terminology implies that most of the avian telencephalon is a hypertrophied basal ganglia, when it is now clear that most of the avian telencephalon is neurochemically, hodologically, and functionally comparable to the mammalian neocortex, claustrum, and pallial amygdala (all of which derive from the pallial sector of the developing telencephalon). Recognizing that this promotes misunderstanding of the functional organization of avian brains and their evolutionary relationship to mammalian brains, avian brain specialists began discussions to rectify this problem, culminating in the Avian Brain Nomenclature Forum held at Duke University in July 2002, which approved a new terminology for avian telencephalon and some allied brainstem cell groups. Details of this new terminology are presented here, as is a rationale for each name change and evidence for any homologies implied by the new names. Revisions for the brainstem focused on vocal control, catecholaminergic, cholinergic, and basal ganglia-related nuclei. For example, the Forum recognized that the hypoglossal nucleus had been incorrectly identified as the nucleus intermedius in the Karten and Hodos (1967) pigeon brain atlas, and what was identified as the hypoglossal nucleus in that atlas should instead be called the supraspinal nucleus. The locus ceruleus of this and other avian atlases was noted to consist of a caudal noradrenergic part homologous to the mammalian locus coeruleus and a rostral region corresponding to the mammalian A8 dopaminergic cell group. The midbrain dopaminergic cell group in birds known as the nucleus tegmenti pedunculopontinus pars compacta was recognized as homologous to the mammalian substantia nigra pars compacta and was renamed accordingly; a group of gamma-aminobutyric acid (GABA)ergic neurons at the lateral edge of this region was identified as homologous to the mammalian substantia nigra pars reticulata and was also renamed accordingly. A field of cholinergic neurons in the rostral avian hindbrain was named the nucleus pedunculopontinus tegmenti, whereas the anterior nucleus of the ansa lenticularis in the avian diencephalon was renamed the subthalamic nucleus, both for their evident mammalian homologues. For the basal (i.e., subpallial) telencephalon, the actual parts of the basal ganglia were given names reflecting their now evident homologues. For example, the lobus parolfactorius and paleostriatum augmentatum were acknowledged to make up the dorsal subdivision of the striatal part of the basal ganglia and were renamed as the medial and lateral striatum. The paleostriatum primitivum was recognized as homologous to the mammalian globus pallidus and renamed as such. Additionally, the rostroventral part of what was called the lobus parolfactorius was acknowledged as comparable to the mammalian nucleus accumbens, which, together with the olfactory tubercle, was noted to be part of the ventral striatum in birds. A ventral pallidum, a basal cholinergic cell group, and medial and lateral bed nuclei of the stria terminalis were also recognized. The dorsal (i.e., pallial) telencephalic regions that had been erroneously named to reflect presumed homology to striatal parts of mammalian basal ganglia were renamed as part of the pallium, using prefixes that retain most established abbreviations, to maintain continuity with the outdated nomenclature. We concluded, however, that one-to-one (i.e., discrete) homologies with mammals are still uncertain for most of the telencephalic pallium in birds and thus the new pallial terminology is largely devoid of assumptions of one-to-one homologies with mammals. The sectors of the hyperstriatum composing the Wulst (i.e., the hyperstriatum accessorium intermedium, and dorsale), the hyperstriatum ventrale, the neostriatum, and the archistriatum have been renamed (respectively) the hyperpallium (hypertrophied pallium), the mesopallium (middle pallium), the nidopallium (nest pallium), and the arcopallium (arched pallium). The posterior part of the archistriatum has been renamed the posterior pallial amygdala, the nucleus taeniae recognized as part of the avian amygdala, and a region inferior to the posterior paleostriatum primitivum included as a subpallial part of the avian amygdala. The names of some of the laminae and fiber tracts were also changed to reflect current understanding of the location of pallial and subpallial sectors of the avian telencephalon. Notably, the lamina medularis dorsalis has been renamed the pallial-subpallial lamina. We urge all to use this new terminology, because we believe it will promote better communication among neuroscientists. Further information is available at http://avianbrain.org

Animals↗
PubMed2004

A redox-controlled molecular switch revealed by the crystal structure of a bacterial heme PAS sensor.

PAS domains, which have been identified in over 1100 proteins from all three kingdoms of life, convert various input stimuli into signals that propagate to downstream components by modifying protein-protein interactions. One such protein is the Escherichia coli redox sensor, Ec DOS, a phosphodiesterase that degrades cyclic adenosine monophosphate in a redox-dependent manner. Here we report the crystal structures of the heme PAS domain of Ec DOS in both inactive Fe(3+) and active Fe(2+) forms at 1.32 and 1.9 A resolution, respectively. The protein folds into a characteristic PAS domain structure and forms a homodimer. In the Fe(3+) form, the heme iron is ligated to a His-77 side chain and a water molecule. Heme iron reduction is accompanied by heme-ligand switching from the water molecule to a side chain of Met-95 from the FG loop. Concomitantly, the flexible FG loop is significantly rigidified, along with a change in the hydrogen bonding pattern and rotation of subunits relative to each other. The present data led us to propose a novel redox-regulated molecular switch in which local heme-ligand switching may trigger a global "scissor-type" subunit movement that facilitates catalytic control.

Amino Acid Sequence↗
PubMed2004

Activation of heme-regulated eukaryotic initiation factor 2alpha kinase by nitric oxide is induced by the formation of a five-coordinate NO-heme complex: optical absorption, electron spin resonance, and resonance raman spectral studies.

Heme-regulated eukaryotic initiation factor 2alpha kinase (HRI) regulates the synthesis of hemoglobin in reticulocytes in response to heme availability. HRI contains a tightly bound heme at the N-terminal domain. Earlier reports show that nitric oxide (NO) regulates HRI catalysis. However, the mechanism of this process remains unclear. In the present study, we utilize in vitro kinase assays, optical absorption, electron spin resonance (ESR), and resonance Raman spectra of purified full-length HRI for the first time to elucidate the regulation mechanism of NO. HRI was activated via heme upon NO binding, and the Fe(II)-HRI(NO) complex displayed 5-fold greater eukaryotic initiation factor 2alpha kinase activity than the Fe(III)-HRI complex. The Fe(III)-HRI complex exhibited a Soret peak at 418 nm and a rhombic ESR signal with g values of 2.49, 2.28, and 1.87, suggesting coordination with Cys as an axial ligand. Interestingly, optical absorption, ESR, and resonance Raman spectra of the Fe(II)-NO complex were characteristic of five-coordinate NO-heme. Spectral findings on the coordination structure of full-length HRI were distinct from those obtained for the isolated N-terminal heme-binding domain. Specifically, six-coordinate NO-Fe(II)-His was observed but not Cys-Fe(III) coordination. It is suggested that significant conformational change(s) in the protein induced by NO binding to the heme lead to HRI activation. We discuss the role of NO and heme in catalysis by HRI, focusing on heme-based sensor proteins.

Animals↗
PubMed2004

Importance of valine 567 in substrate recognition and oxidation by neuronal nitric oxide synthase.

Nitric oxide (NO) is synthesised by a two-step oxidation of -arginine (L-Arg) in the active site of nitric oxide synthase (NOS) with formation of an intermediate, N omega-hydroxy-L-Arg (NOHA). Crystal structures of NOSs have shown the importance of an active-site Val567 residue (numbered for rat neuronal NOS, nNOS) interacting with non-amino acid substrates. To investigate the role of this Val residue in substrate recognition and NO-formation activity by nNOS, we generated and purified four Val567 mutants of nNOS, Val567Leu, Val567Phe, Val567Arg and Val567Glu. We characterized these proteins and tested their ability to generate NO from the oxidation of natural substrates L-Arg and NOHA, and from N-hydroxyguanidines previously identified as alternative substrates for nNOS. The Val567Leu mutant displayed lower NO formation activities than the wild type (WT) in the presence of all tested compounds. Surprisingly, the Val567Phe mutant formed low amounts of NO only from NOHA. These two mutants displayed lower affinity for L-Arg and NOHA than the WT protein. Val576Glu and Val567Arg mutants were much less stable and did not lead to any formation of NO. These results suggest that Val567 is an important residue for preserving the integrity of the active site, for substrate binding, and subsequently for NO-formation in nNOS.

Amino Acid Substitution↗
PubMed2004

Analysis of the kinetics of CO binding to neuronal nitric oxide synthase by flash photolysis: dual effects of substrates, inhibitors, and tetrahydrobiopterin.

The effects of substrates, inhibitors and tetrahydrobiopterin (H4B) on CO rebinding to the isolated heme-bound oxygenase domain (nNOSox) of neuronal nitric oxide synthase were examined by laser flash photolysis. The rate constant of CO recombination with substrate and inhibitor-free nNOSox in the absence of H4B was 1.0 x 10(6) M(-1) s(-1). The addition of H4B led to a marked decrease in the rate to 0.59 x 10(6) M(-1) s(-1). Interestingly, the substrates, L-Arg and N-hydroxy-L-Arg (NHA), altered CO binding behavior in that the binding rate was modified to CO concentration-independent, both with and without H4B. In the absence of H4B, agmatine, NG-monomethyl-L-Arg (NMMA) and NG-nitro-L-Arg methyl ester (NAME) decreased the CO concentration-dependent rate constants of rebinding by half (0.43 x 10(6) M(-1) s(-1) for the NMMA-bound complex), whereas N6-(l-iminoethyl)-L-Lys (NIL) and 7-nitro-1H-indazole (7-NI) increased the rate constants by more than 70% (up to 2.1 x 10(6) M(-1) s(-1) for the NIL-bound complex). In the presence of H4B, the binding rate was independent of CO concentration for the agmatine-bound complex. The differential effects of the inhibitors on the CO concentration-dependent rate constants were significantly diminished for the H4B-bound system. Interestingly, these variable effects of inhibitors on the CO binding rate were more pronounced in the absence of H4B. Accordingly, we suggest that H4B significantly influences CO binding by altering the CO access channel, and further reduces the divergent effects of different inhibitors.

Animals↗
PubMed2004

What does a pigeon (Columba livia) brain look like during homing? selective examination of ZENK expression.

Lesion studies have shown that the avian hippocampus plays a crucial role in homing pigeon (Columba livia) navigation. Using the expression of the immediate early gene protein ZENK in intact pigeons, the authors found regional variation in hippocampal activation as a consequence of homing and, necessarily, the behavior and internal states that accompany it. Specifically, pigeons that homed displayed a significant increase in the number of ZENK-labeled cells in the lateral hippocampal formation compared with pigeons that did not home, whereas no difference was seen in the medial hippocampus. Significant changes in ZENK expression were also found in the medial striatum, which resembles the mammalian ventral striatum. The results identify portions of the hippocampal formation and the medial striatum as sites of plasticity associated with homing.

Animals↗
PubMed2004

Critical roles of Asp40 at the haem proximal side of haem-regulated phosphodiesterase from Escherichia coli in redox potential, auto-oxidation and catalytic control.

In haem-regulated phosphodiesterase (PDE) from Escherichia coli (Ec DOS), haem is bound to the PAS domain, and the redox state of the haem iron regulates catalysis by the PDE domain. We generated mutants of Asp40, which forms a hydrogen bond with His77 (a proximal haem axial ligand) via two water molecules, and a salt bridge with Arg85 at the protein surface. The redox potential of haem was markedly increased from 67 mV vs. the standard hydrogen electrode in the wild-type enzyme to 95 mV and 114 mV in the Ala and Asn mutants, respectively. Additionally, the auto-oxidation rate of Ec DOS PAS was significantly increased from 0.0053 to 0.051 and 0.033 min(-1), respectively. Interestingly, the catalytic activities of the Asp40 mutants were abolished completely. Thus, Asp40 appears to play a critical role in the electronic structure of the haem iron and redox-dependent catalytic control of the PDE domain. In this report, we discuss the mechanism of catalytic control of Ec DOS, based on the physico-chemical characteristics of the Asp40 mutants.

Aspartic Acid↗
PubMed2003

Identification of caveolin-1-interacting sites in neuronal nitric-oxide synthase. Molecular mechanism for inhibition of NO formation.

Caveolin is known to down-regulate both neuronal (nNOS) and endothelial nitric-oxide synthase (eNOS). In the present study, direct interactions of recombinant caveolin-1 with both the oxygenase and reductase domains of nNOS were demonstrated using in vitro binding assays. To elucidate the mechanism of nNOS regulation by caveolin, we examined the effects of a caveolin-1 scaffolding domain peptide (CaV1p1; residues (82-101)) on the catalytic activities of wild-type and mutant nNOSs. CaV1p1 inhibited NO formation activity and NADPH oxidation of wild-type nNOS in a dose-dependent manner with an IC(50) value of 1.8 microM. Mutations of Phe(584) and Trp(587) within a caveolin binding consensus motif of the oxygenase domain did not result in the loss of CaV1p1 inhibition, indicating that an alternate region of nNOS mediates inhibition by caveolin. The addition of CaV1p1 also inhibited more than 90% of the cytochrome c reductase activity in the isolated reductase domain with or without the calmodulin (CaM) binding site, whereas CaV1p1 inhibited ferricyanide reductase activity by only 50%. These results suggest that there are significant differences in the mechanism of inhibition by caveolin for nNOS as compared with those previously reported for eNOS. Further analysis of the interaction through the use of several reductase domain deletion mutants revealed that the FMN domain was essential for successful interaction between caveolin-1 and nNOS reductase. We also examined the effects of CaV1p1 on an autoinhibitory domain deletion mutant (Delta40) and a C-terminal truncation mutant (DeltaC33), both of which are able to form NO in the absence of CaM, unlike the wild-type enzyme. Interestingly, CaV1p1 inhibited CaM-dependent, but not CaM-independent, NO formation activities of both Delta40 and DeltaC33, suggesting that CaV1p1 inhibits interdomain electron transfer induced by CaM from the reductase domain to the oxygenase domain.

Animals↗
PubMed2003

Binding of oxygen and carbon monoxide to a heme-regulated phosphodiesterase from Escherichia coli. Kinetics and infrared spectra of the full-length wild-type enzyme, isolated PAS domain, and Met-95 mutants.

The heme-regulated phosphodiesterase, Ec DOS, is a redox sensor that uses the heme in its PAS domain to regulate catalysis. The rate of O(2) association (k(on)) with full-length Ec DOS is extremely slow at 0.0019 microM(-1) s(-1), compared with >9.5 microM(-1) s(-1) for 6-coordinated globin-type hemoproteins, as determined by the stopped-flow method. This rate is dramatically increased (up to 16-fold) in the isolated heme-bound PAS domain. Dissociation constants (K(d)) calculated from the kinetic parameters are 340 and 20 microm for the full-length wild-type enzyme and its isolated PAS domain, respectively. Mutations at Met-95 in the isolated PAS domain, which may be a heme axial ligand in the Fe(II) complex, lead to a further increase in the k(on) value by more than 30-fold, and consequently, a decrease in the K(d) value to less than 1 microM. The k(on) value for CO binding to the full-length wild-type enzyme is also very low (0.00081 microM(-1) s(-1)). The kinetics of CO binding to the isolated PAS domain and its mutants are similar to those observed for O(2). However, the K(d) values for CO are considerably lower than those for O(2).

Carbon Monoxide↗
PubMed2003

Relationships between heme incorporation, tetramer formation, and catalysis of a heme-regulated phosphodiesterase from Escherichia coli: a study of deletion and site-directed mutants.

The heme-regulated phosphodiesterase (PDE) from Escherichia coli (Ec DOS) is a tetrameric protein composed of an N-terminal sensor domain (amino acids 1-201) containing two PAS domains (PAS-A, amino acids 21-84, and PAS-B, amino acids 144-201) and a C-terminal catalytic domain (amino acids 336-799). Heme is bound to the PAS-A domain, and the redox state of the heme iron regulates PDE activity. In our experiments, a H77A mutation and deletion of the PAS-B domain resulted in the loss of heme binding affinity to PAS-A. However, both mutant proteins were still tetrameric and more active than the full-length wild-type enzyme (140% activity compared with full-length wild type), suggesting that heme binding is not essential for catalysis. An N-terminal truncated mutant (DeltaN147, amino acids 148-807) containing no PAS-A domain or heme displayed 160% activity compared with full-length wild-type protein, confirming that the heme-bound PAS-A domain is not required for catalytic activity. An analysis of C-terminal truncated mutants led to mapping of the regions responsible for tetramer formation and revealed PDE activity in tetrameric proteins only. Mutations at a putative metal-ion binding site (His-590, His-594) totally abolished PDE activity, suggesting that binding of Mg2+ to the site is essential for catalysis. Interestingly, the addition of the isolated PAS-A domain in the Fe2+ form to the full-length wild-type protein markedly enhanced PDE activity (>5-fold). This activation is probably because of structural changes in the catalytic site as a result of interactions between the isolated PAS-A domain and that of the holoenzyme.

Binding Sites↗
PubMed2003

Single-turnover of nitric-oxide synthase in the presence of 4-amino-tetrahydrobiopterin: proposed role for tetrahydrobiopterin as a proton donor.

Tetrahydrobiopterin (BH4) is an essential cofactor of nitric-oxide synthase (NOS) that serves as a one-electron donor to the oxyferrous.heme complex. 4-Aminotetrahydrobiopterin (4-amino-BH4) is a potent inhibitor of NO synthesis, although it mimics all allosteric and structural effects of BH4 and exhibits comparable redox properties. We studied the reaction of reduced endothelial NOS oxygenase domain with O2 in the presence of 4-amino-BH4 at -30 degrees C by optical and electron paramagnetic resonance (EPR) spectroscopy. With Arg as the substrate, we observed a trihydropteridine radical with a corresponding heme species that was oxyferrous, with a Soret maximum at 428 nm and no EPR signal. With NG-hydroxy-l-arginine (NHA) no pterin radical appeared, whereas an axial ferrous heme.NO complex was formed. The corresponding optical spectra, with Soret bands at 417/423 nm, suggest that the proximal sulfur ligand is protonated. Accordingly, 4-amino-BH4 serves as a one-electron donor to Fe(II).O2 with both Arg and NHA, but the reaction cycle cannot be completed with either substrate. We propose that protonation of Fe(II)O2- is inhibited in the presence of 4-amino-BH4. With Arg, dissociation of O2- and binding of O2 yields Fe(II).O2 and a pteridine radical; with NHA, reaction of the substrate with heme-bound O2- eventually yields Fe(II).NO and reduced 4-amino-BH4. These results suggest that BH4 donates a proton to Fe(II).O2- during catalysis and that inhibition by 4-amino-BH4 may be due to its inability to support this essential protonation step.

Biopterins↗
PubMed2003

CO binding study of mouse heme-regulated eIF-2alpha kinase: kinetics and resonance Raman spectra.

Heme-regulated eukaryotic initiation factor (eIF)-2alpha kinase (HRI) regulates the synthesis of globin chains in reticulocytes with heme availability. In the present study, CO binding kinetics to the 6-coordinated Fe(II) heme of the amino-terminal domain of mouse HRI and resonance Raman spectra of the Fe(II)-CO complex are examined to probe the character of the heme environment. The CO association rate constant, k(on)', and CO dissociation rate constant, k(off), were 0.0029 microM(-1)s(-1) and 0.003 s(-1), respectively. These values are very slow compared with those of mouse neuroglobin and sperm whale myoglobin, while the k(off) value of HRI was close to those of the 6-coordinated hemoglobins from Chlamydomonas and barley (0.0022 and 0.0011 s(-1)). The dissociation rate constant of an endogenous ligand, which occurs prior to CO association, was 18.3 s(-1), which was lower than those (197 and 47 s(-1)) of the same 6-coordinated hemoglobins. Resonance Raman spectra suggest that the Fe-C-O adopts an almost linear and upright structure and that the bound CO interacts only weakly with nearby amino acid residues.

Animals↗
PubMed2003

Cyanide binding study of neuronal nitric oxide synthase: effects of inhibitors and mutations at the substrate binding site.

In order to understand the heme distal structure of neuronal nitric oxide synthase (nNOS), we studied cyanide binding to the ferric wild-type and substrate binding site mutants, Glu592Ala and Tyr588His, of the isolated oxygenase domain in the absence and presence of substrates and inhibitors. Cyanide bound to isolated heme-bound oxygenase domains (nNOSox) in the absence of the substrates with the dissociation constant (K(d)) of 3.1 mM. The presence of the substrates, L-Arg and NHA, did not change the K(d) value. However, cyanide binding was almost abolished in the presence of inhibitors such as NAME, thiocitrulline and 7-NI. The effect of the inhibitors were not observed for the Glu592Ala mutant, while similar strong inhibiting effects were observed for the Tyr588His mutant. We discuss the binding fashion of those inhibitors to the heme substrate binding site of nNOS.

Arginine↗
PubMed2003

CO binding to the isolated oxygenase domain of neuronal nitric oxide synthase: effects of inhibitors and mutations at the substrate-binding site.

In order to understand the heme distal structure of neuronal nitric oxide synthase (nNOS), we studied the binding affinity of CO for the ferrous wild type enzyme and the Glu592Ala and Tyr588His substrate binding-site mutants (generated in the oxygenase domain, nNOSox) in the presence of substrates and inhibitors. The CO binding affinities (K(d) = 10-21 mM) of nNOSox in the presence of the substrates, L-Arg and NHA, or inhibitors such as NAME and agmatine were more than two-fold lower than in their absence (K(d) = 5 mM). The presence of NIL strongly inhibited CO binding and gave a K(d) of more than 100 mM. These effects were not observed for the Glu592Ala mutant. The trend in CO binding affinities observed for the Tyr588His mutant was similar to that of the wild type enzyme. The presence of the isolated reductase domain did not affect CO binding. We discuss the role of substrate and inhibitor binding in CO complexation as well as in catalysis.

Amino Acid Sequence↗
PubMed2003

Organization of the ectostriatum based on afferent connections in the zebra finch (Taeniopygia guttata).

In birds with laterally-located eyes, such as zebra finches and pigeons, the tectofugal visual pathway is the most prominent route from the retina to the telencephalon. However, little is known about exactly how the visual information is processed in this pathway, especially at the core region of the ectostriatum (Ec) in the telencephalon. In order to reveal a detailed organization of Ec, we decided to systematically analyze the afferent connections of Ec by injecting small amounts of sensitive tracers (biotinylated dextran amine and cholera toxin subunit B) selectively into different regions of Ec and the thalamic center of the tectofugal pathway (the nucleus rotundus, Rt). The present study revealed a clearer picture of the organization of Ec subdivisions than previously known. The present results showed that the anterior portion of Rt sent a heavy projection to the ventral region of the anterior Ec, whereas the more caudal subdivisions of Rt sent projections to more caudal and dorsal portions in Ec. The results suggest that Ec subdivisions appear to be arranged along an axis 'rotated' in the anterior direction, almost parallel to other major telencephalic laminae. These results may clarify the physiological and chemical heterogeneity of Ec found in the previous studies. The present findings also provide an insight into the possible organization of a visual processing center in a non-mammal.

Afferent Pathways↗
PubMed2003

Characterization of Met95 mutants of a heme-regulated phosphodiesterase from Escherichia coli. Optical absorption, magnetic circular dichroism, circular dichroism, and redox potentials.

On the basis of amino acid sequences and crystal structures of similar enzymes, it is proposed that Met95 of the heme-regulated phosphodiesterase from Escherichia coli (Ec DOS) acts as a heme axial ligand. In accordance with this proposal, the Soret and visible optical absorption and magnetic circular dichroism spectra of the Fe(II) complexes of the Met95Ala and Met95Leu mutant proteins indicate that these complexes are five-coordinated high-spin, suggesting that Met95 is an axial ligand for the Fe(II) complex. However, the Fe(III) complexes of these mutants are six-coordinated low-spin, like the wild-type enzyme. The latter spectral findings are inconsistent with the proposal that the axial ligand to the Fe(III) heme is Met95. To determine the possibility of a redox-dependent ligand switch in Ec DOS, we further analyzed Soret CD spectra and redox potentials, which provide direct evidence on the environmental structure of the heme protein. CD spectra of Fe(III) Met95 mutants were all different from those of the wild-type protein, suggesting indirect coordination of Met95 to the Fe(III) wild-type heme. The redox potentials of the Met95Leu, Met95Ala and Met95His mutants were considerably lower than that of the wild-type enzyme (+70 mV) at -1, -26, and -122 mV vs. SHE, respectively. Thus, it is reasonable to speculate that water (or hydroxy anion) interacting with Met95, rather than Met95 itself, is the axial ligand to the Fe(III) heme.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2003

Human leukocyte antigen and aseptic loosening in Charnley total hip arthroplasty.

Human leukocyte antigen phenotypes and radiographic course were studied in 70 Japanese patients (90 hips) who had Charnley low friction arthroplasty. Of the 28 hips diagnosed as radiographically loose less than 15 years after surgery, seven hips (25.0%) were in patients who had a positive human leukocyte antigen A31(19). Of the 62 hips that were radiographically stable more than 15 years, two hips (3.2%) were in patients who had a positive human leukocyte antigen A31(19). Of the nine hips in patients who were positive to human leukocyte antigen A31(19), seven hips were diagnosed as radiographically loose (loosening rate was 77.8%) 15 years after surgery. On the other hand, of the 81 hips in the patients who were negative to human leukocyte antigen A31(19), only 21 hips were diagnosed as radiographically loose (loosening rate was 25.9%) 15 years after surgery. These data suggest that individual immune response to implant materials, linked to human leukocyte antigen, may participate in the process of aseptic loosening in Charnley low friction arthroplasty.

Adult↗