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Biomedical subjects

B I Lee

Publications and source records attributed to B I Lee.

At least 37 records · Page 2Linked to original sources
PubMed2000

The effects of the number and ratio of repaired arteries and veins on the survival rate in digital replantation.

From January 1990 to December 1998, 631 consecutive single-digit replantations were reviewed retrospectively to determine the essential number of vascular anastomoses and the artery-to-vein ratio for successful finger replantation. The correlations between the number and the ratio of anastomosed vessels and the survival rate were examined according to the amputated digital levels, and all of the correlated results were compared with each other statistically. In zone I, the survival rate of the digits with a vein repaired was higher than that of digits treated with the external bleeding method. In zone II, repairing more arteries than veins led to venous congestion and resulted in a failure of replantation. Thus, the ratio of an equal or greater number of veins repaired to the arteries repaired was an important factor in successful replantation in zone II, which may be due to the large amount of arterial input relative to the small volume of venous drainage via small veins in the replanted digit. In zone III, the equal number of arteries and veins repaired was also an important factor in successful replantation. However, unlike zone II, even when more arteries were repaired than veins, venous congestion occurred rarely because the vein in this area was larger, providing sufficient venous drainage. In zone IV, repair of two veins was needed to yield good results. Because the volume of the amputated part in zone IV was larger than in other zones, it was desirable to repair both arteries, even though repairing one artery yielded good results. In conclusion, it is desirable to repair as many vessels as possible to increase the possibility of a good result. However, digital amputations and their conditions for replantation differ. Therefore, the number and ratio of vessels that need to be repaired should be modified and adjusted in each case.

Amputation, Traumatic↗
PubMed2000

Correlation of electrodiagnostic findings with subjective symptoms in carpal tunnel syndrome.

The records of 138 patients (222 hands) who had been evaluated by preoperative nerve conduction study (NCS) and consecutive self-administered questionnaires were analyzed to determine diagnostic relations in carpal tunnel syndrome. Hands were categorized into six grades (extreme, severe, moderate, mild, minimal, and negative) according to the three modalities: the NCS data of the median sensory nerve, Symptom Severity Scale score, and Functional Status Scale score. The authors evaluated the correlation, independence, homogeneity, and association among parameters, and found the following: (1) the NCS data correlated more significantly (p < 0.05) and was associated more linearly with Symptom Severity Scale score than the Functional Status Scale score; (2) the choice of modality exerted an influence on grading severities, thus grades varied according to the modalities; and (3) the distribution of patients was not homogenous; there were more extremes in NCS, and more severe scores on the Symptom Severity Scale. Patients rated as one homogeneous severity by NCS data may be interpreted into different severities (from negative to extreme) by self-administered questionnaires and vice versa.

Adult↗
PubMed2000

Lactate dehydrogenase from the hyperthermophilic archaeon Methanococcus jannaschii: overexpression, crystallization and preliminary X-ray analysis.

L(+)-Lactate dehydrogenase (LDH) is a key enzyme in anaerobic metabolism which converts pyruvate to lactate. LDH from the hyperthermophilic archaebacterium Methanococcus jannaschii has been overexpressed in Escherichia coli and crystallized in two crystal forms at 297 K using 2-methyl-2,4-pentanediol as precipitant. Type I crystals grew rapidly and diffracted to at least 2.8 A Bragg spacing upon exposure to Cu Kalpha X-rays. X-ray diffraction data to 2.9 A have been collected from a native crystal. The type I crystal is tetragonal, belonging to the space group P4(2)2(1)2, with unit-cell parameters a = b = 99.74, c = 170.00 A. The asymmetric unit contains two LDH subunits, with a corresponding crystal volume per protein mass (V(m)) of 3.05 A(3) Da(-1) and a solvent content of 59.7%. Type II crystals, which grew more slowly, diffracted to at least 1.8 A Bragg spacing upon exposure to Cu Kalpha X-rays. X-ray diffraction data to 1.9 A have been collected from a native crystal. The type II crystal is orthorhombic, belonging to the space group P2(1)2(1)2, with unit-cell parameters a = 47.65, b = 125.10, c = 58.08 A. The asymmetric unit contains a single LDH subunit, with a corresponding crystal volume per protein mass (V(m)) of 2.50 A(3) Da(-1) and a solvent content of 50.8%. Therefore, the type II crystal is more suitable for high-resolution structure determination than the type I crystal.

Cloning, Molecular↗
PubMed2000

MRI features of infarcts with potential cardiac source of embolism in the Yonsei Stroke Registry (YSR), Korea.

The determination of the embolic source is crucial to understanding the pathogenesis of ischemic stroke, the initiation of appropriate therapy, and the prevention of recurrent infarctions. In this study we undertook to identify the characteristic features on magnetic resonance images of patients who had suffered from stroke due to cardiac embolism (CE), as classified by TOAST (possible and probable). We retrospectively studied magnetic resonance imaging (MRI) findings of patients with ischemic stroke from the Yonsei Stroke Registry (YSR). On the basis of the TOAST classification, 92 patients were identified to have a potential cardiac source of embolism (PCSE), in which 69 patients were found to have high-risk PCSE and 23 patients medium-risk PCSE. To compare their imaging characteristics, another group of 49 patients who were found to have had a stroke due to large artery-to-artery (ATA) embolism-common or internal carotid artery (CCA, ICA)-were identified. Involvement of the simultaneous superficial and deep territories (58.7%; 6.1%, p < 0.001), and combined new anterior and old posterior circulation (15.2%; 2.0%, p = 0.016) were more frequent in PCSE than ATA embolism. Bilateral anterior hemispheric involvement was also more frequent in the PCSE group, but it did not reach statistical significance (13.0%; 4.1%, p = 0.090). ATA embolism tended to involve only superficial territories compared to PCSE (71.4%; 28.3%, p < 0.001). There were no topographic differences between the high-risk and medium-risk groups. With respect to the etiology of PCSE in our population, atrial fibrillation was the most common. Characteristic MRI features of patients with PCSE, which were not documented previously by computed tomography (CT) included: old and new, involvement of multiple different vascular territories, bilateral anterior hemisphere, as well as anterior and posterior circulation. These MRI features, together with simultaneous superficial and deep territorial involvement, help to differentiate the underlying embolic sources, whether they are cardiac or ATA in origin.

Cerebral Infarction↗
PubMed1999

The RAD2 domain of human exonuclease 1 exhibits 5' to 3' exonuclease and flap structure-specific endonuclease activities.

The RAD2 family of nucleases includes human XPG (Class I), FEN1 (Class II), and HEX1/hEXO1 (Class III) products gene. These proteins exhibit a blend of substrate specific exo- and endonuclease activities and contribute to repair, recombination, and/or replication. To date, the substrate preferences of the EXO1-like Class III proteins have not been thoroughly defined. We report here that the RAD2 domain of human exonuclease 1 (HEX1-N2) exhibits both a robust 5' to 3' exonuclease activity on single- and double-stranded DNA substrates as well as a flap structure-specific endonuclease activity but does not show specific endonuclease activity at 10-base pair bubble-like structures, G:T mismatches, or uracil residues. Both the 5' to 3' exonuclease and flap endonuclease activities require a divalent metal cofactor, with Mg(2+) being the preferred metal ion. HEX1-N2 is approximately 3-fold less active in Mn(2+)-containing buffers and exhibits <5% activity in the presence of Co(2+), Zn(2+), or Ca(2+). The optimal pH range for the nuclease activities of HEX1-N2 is 7.2-8.2. The specific activity of its 5' to 3' exonuclease function is 2.5-7-fold higher on blunt end and 5'-recessed double-stranded DNA substrates compared with duplex 5'-overhang or single-stranded DNAs. The flap endonuclease activity of HEX1-N2 is similar to that of human flap endonuclease-1, both in terms of turnover efficiency (k(cat)) and site of incision, and is as efficient (k(cat)/K(m)) as its exonuclease function. The nuclease activities of HEX1-N2 described here indicate functions for the EXO1-like proteins in replication, repair, and/or recombination that may overlap with human flap endonuclease-1.

Amino Acid Sequence↗
PubMed1999

Expression specificity of the mouse exonuclease 1 (mExo1) gene.

Genetic recombination involves either the homo-logous exchange of nearly identical chromosome regions or the direct alignment, annealing and ligation of processed DNA ends. These mechanisms are involved in repairing potentially lethal or mutagenic DNA damage and generating genetic diversity within the meiotic cell population and antibody repertoire. We report here the identification of a mouse gene, termed mExo1 for mouse exonuclease 1, which encodes a approximately 92 kDa protein that shares homology to proteins of the RAD2 nuclease family, most notably human 5' to 3' exonuclease Hex1/hExo1, yeast exonuclease 1 (Exo1) proteins and Drosophila melanogaster Tosca. The mExo1 gene maps to distal chromosome 1, consistent with the recent mapping of the orthologous HEX1 / hEXO1 gene to chromosome 1q42-q43. mExo1 is expressed prominently in testis, an area of active homologous recombination, and spleen, a prominent lymphoid tissue. An increased level of mExo1 mRNA was observed during a stage of testis development where cells that are actively involved in meiotic recombination arise first and represent a significant proportion of the germ cell population. Comparative evaluation of the expression patterns of the human and mouse genes, combined with previous biochemical and yeast genetic studies, indicate that the Exo1-like proteins are important contributors to chromosome processing during mammalian DNA repair and recombination.

Amino Acid Sequence↗
PubMed1999

Differential interfacial and substrate binding modes of mammalian pancreatic phospholipases A2: a comparison among human, bovine, and porcine enzymes.

To identify the residues essential for interfacial binding and substrate binding of human pancreatic phospholipase A2 (hpPLA2), several ionic residues in the putative interfacial binding surface (R6E, K7E, K10E, and K116E) and substrate binding site (D53K and K56E) were mutated. Interfacial affinity of these mutants was measured using anionic polymerized liposomes, and their enzymatic activity was measured using various substrates including phospholipid monomers, zwitterionic and anionic micelles, and anionic polymerized mixed liposomes. Similar mutations (R6E, K10E, K56E, and K116E) were made to porcine pancreatic phospholipase A2 (ppPLA2), and the properties of mutants were measured by the same methods. Results indicate that hpPLA2 and ppPLA2 have similar interfacial binding mechanisms in which cationic residues in the amino terminus and Lys-116 in the carboxy terminus are involved in binding to anionic lipid surfaces. Small but definite differences between the two enzymes were observed in overall interfacial affinity and activity and the effects of the mutations on interfacial enzyme activity. The interfacial binding of hpPLA2 and ppPLA2 is distinct from that of bovine pancreatic phospholipase A2 in that Lys-56 is involved in the interfacial binding of the latter enzyme. The unique phospholipid headgroup specificity of hpPLA2 derives from the presence of Asp-53 in the substrate binding site. This residue appears to participate in stabilizing electrostatic interactions with the cationic ethanolamine headgroup, hence the phosphatidylethanolamine preference of hpPLA2. Taken together, these studies reveal the similarities and the differences in the mechanisms by which mammalian pancreatic phospholipases A2 interact with lipid aggregates and perform interfacial catalysis.

Animals↗
PubMed1999

A structural determinant of the unique interfacial binding mode of bovine pancreatic phospholipase A2.

The catalytic steps of the phospholipase A2 (PLA2)-catalyzed hydrolysis of phospholipids are preceded by interfacial binding. Among various pancreatic PLA2s, bovine pancreatic PLA2 (bpPLA2) has a unique interfacial binding mode in which Lys-56 plays an important role in its binding to anionic lipid surfaces. To identify the structural determinant of this unique interfacial binding mode of bpPLA2, we systematically mutated bpPLA2 and measured the effects of mutations on its interfacial binding and activity. First, different cationic clusters were generated in the amino-terminal alpha-helix by the N6R, G7K, and N6R/G7K mutations. These mutations enhanced the binding of bpPLA2 to anionic liposomes up to 15-fold. For these mutants, however, the K56E mutation still caused a large drop in interfacial affinity for and activity toward anionic liposomes, indicating that the generation of a cationic patch in the amino-terminal alpha-helix of bpPLA2 did not change its interfacial binding mode. Second, residues 62-66 that form a part of the pancreatic loop were deleted. For this deletion mutant (Delta62-66), which was as active as wild-type toward anionic liposomes, the K56E and K116E mutations (Delta62-66/K56E and Delta62-66/K116E) did not have significant effects on interfacial affinity. In contrast, the K10E mutation showed a much larger decrease in interfacial affinity (10-fold), indicating the deletion of residues 62-66 caused a major change in the interfacial binding mode. Finally, hydrophobic residues in positions 63 and 65 were replaced by bulkier ones (V63F and V63F/V65L) to pinpoint the structural determinant of the interfacial binding mode of bpPLA2. The effects of K10E and K56E mutations on the interfacial affinity and activity of these mutants showed that Val-63 and Val-65 of bpPLA2 are the structural determinant of its unique interfacial binding mode and that relatively conservative substitutions at these positions result in large changes in the interfacial binding mode among mammalian pancreatic PLA2s. Taken together, this study reveals how minor structural differences among homologous PLA2s can lead to distinct interfacial binding behaviors.

Amino Acid Sequence↗
PubMed1999

Serial brain SPECT images in a case of Sydenham chorea.

BACKGROUND: The pathophysiological nature of Sydenham chorea (SC) has been presumed to be an autoimmune-mediated inflammatory process. Positron emission tomography in SC has revealed a striatal hypermetabolism that might explain the transient neuronal dysfunction. However, any focal hyperperfusion in the striatum or its related structures has not been demonstrated in previous single photon emission computed tomographic (SPECT) imaging studies, which raised a concern about the pathogenesis of the striatal hypermetabolism. OBJECTIVE: To investigate the cerebral perfusion patterns of the subcortical structures by using serial technetium Tc 99m-ethyl cysteinate dimer SPECT in a case of SC, which may provide a clue for the pathophysiological mechanisms. DESIGN: A case report and serial SPECT studies. CASE PRESENTATION: A girl aged 4 years 3 months showed severe generalized choreic movements with concomitant signs of acute pharyngitis. Results of a laboratory study taken 7 days after the onset of chorea showed elevated antistreptolysin O titer, C-reactive protein levels, and erythrocyte sedimentation rate. Other laboratory data, throat culture, echocardiography, brain magnetic resonance imaging, and electroencephalography did not reveal any abnormalities. Five days after treatment with haloperidol and penicillin, the chorea began to improve slowly, and completely resolved in 2 months. RESULTS: Three serial SPECT images and semiquantitative analysis of cerebral perfusion were obtained. Cerebral perfusion in the striatum and thalamus was markedly increased bilaterally during the stage of active chorea and then returned nearly to its baseline level during the convalescent phase. These cerebral perfusion patterns were concordant with semiquantitative analysis. CONCLUSIONS: Hyperperfusion in both the striatum and thalamus in our patient may reflect the subcortical inflammatory processes in SC. The unequivocal SPECT findings in our patient are difficult to reconcile with the negative findings of previous SPECT studies but may suggest the heterogeneity of the perfusion patterns in SC.

Autoimmune Diseases↗
PubMed1999

Evaluation of reperfusion and recovery of brain function before and after intracarotid arterial urokinase therapy in acute cerebral infarction with brain SPECT.

PURPOSE: Perfusion defects can be demonstrated reliably at an early stage with regional cerebral blood flow studies using SPECT. The administration of thrombolytic therapy in ischemic stroke is targeted at restoring cerebral perfusion immediately, leading to salvage of ischemic penumbra, smaller infarct size, and improved clinical outcome. This study considered the role of brain perfusion SPECT in the evaluation of reperfusion and brain function recovery of the infarcted area after early recanalization (less than 6 hours) of the occluded artery using intracarotid arterial urokinase therapy (ICAU). METHODS: Intracranial artery occlusion was confirmed in seven patients using emergency carotid angiography performed within the initial 6-hour period. Intracarotid arterial urokinase (500,000 to 800,000 units) was administered into the occluded arterial system (the left middle cerebral artery in four and the right middle cerebral artery in three patients). CT scanning was performed when the patients arrived in the emergency department and was repeated 24 to 48 hours after ICAU and at 7 days or earlier if clinically indicated. All patients had two SPECT studies, the first before urokinase administration and the second 24 or 48 hours later. RESULTS: Complete recanalization of the occluded vessels was seen in one patient after ICAU, effective partial recanalization was achieved in four patients, and minimal recanalization occurred in the other two. Before ICAU, Tc-99m HMPAO brain SPECT showed decreased uptake of the infarcted area in all patients, whereas the follow-up brain SPECT performed 24 or 48 hours after ICAU revealed improvement in the uptake of the recanalized area on qualitative and semiquantitative assessments using an asymmetry index, suggestive of brain function recovery and clinical improvement. Hemorrhagic transformation adjacent to the reperfused regions occurred in two patients with partial recanalization of the left middle cerebral artery. CONCLUSIONS: Reperfusion of the recanalized area and brain function recovery could be achieved if the occluded artery is recanalized within the initial 6-hour period using ICAU, and this was documented using brain perfusion SPECT without a delay in the therapeutic time window. Because the number of patients we studied was limited, further study is necessary to evaluate the effect of ICAU and to determine its prognostic significance.

Acute Disease↗
PubMed1999

The prognosis for control of seizures with medications in patients with MRI evidence for mesial temporal sclerosis.

PURPOSE: Mesial temporal sclerosis (MTS) is the most common and important pathology in temporal lobe epilepsy (TLE), and its presence in magnetic resonance imaging (MRI) scans is strongly correlated with a successful surgical outcome. Despite the general assumption that patients with MTS respond poorly to medication, the long-term prognosis for such patients has not yet been investigated. We studied the overall clinical prognosis of patients with MTS and analyzed the factors related to the degree of medical responsiveness. METHODS: Case patients were actively followed up at the Yonsei Epilepsy Clinic in Seoul, Korea, for >2 years. A structured interview and a thorough clinical evaluation were conducted. MRI scans, at the field strength of 1.0 or 1.5 Tesla, were performed with T1- and T2-weighted coronal and axial spin-echo images. All coronal slices were < or = 5-mm thick with no gap. Two neurologists and one radiologist determined the presence of MTS in MRIs by visual analysis. RESULTS: The MTS group consisted of 104 patients. Of these, 26 (25%) were completely controlled with adequate therapy, and 40 (38%) were intractable, despite aggressive anticonvulsant polytherapy. The remaining 37% had their seizure frequencies reduced by > or = 50%, but were not seizure free. The age of seizure onset was significantly younger in the intractable group than in the well-controlled group. Patients with a history of febrile convulsions or with epileptiform discharges in their electroencephalogram (EEG) had poorer seizure control (p < 0.05) than those who did not. Among the 16 patients who had no previous treatment, five (31%) became seizure free, and two were intractable. CONCLUSIONS: Not all patients with MTS are medically intractable; 25% of the patients in our study achieved complete control while receiving medication. Poor seizure control was related to an early age of seizure onset, a history of febrile convulsions, and epileptiform discharges on the EEG.

Adolescent↗
PubMed1998

Bent stents: a method to facilitate delivery of the Palmaz-Schatz stent in tortuous and rigid coronary arteries.

The Palmaz-Schatz stent delivery system (PS 153) and "bare" PS 204 stents are relatively high-profile, rigid devices that can be difficult to deliver to lesions beyond tortuous, irregular, or rigid proximal segments. Described herein is a method of mounting and shaping a Palmaz-Schatz stent on a low-profile balloon that provides a steerable, low-profile, and secure stent delivery system. Also described is the successful use of this method in four consecutive cases where Palmaz-Schatz stents could not be delivered to the lesion site due to severely angulated, irregular, or rigid proximal vessel segments.

Aged↗
PubMed1998

Localized pigmented villonodular synovitis of the knee: arthroscopic treatment.

Pigmented villonodular synovitis (PVNS) is a relatively rare condition. It occurs in two forms: a diffuse form involves the entire synovium and occurs in the majority of cases, and a localized form involves a discrete section of the synovium. The disorder almost always involves a single joint and the knee is most commonly affected. We report on three cases of localized PVNS that involved the patellar fat pad and synovium. Diagnostic and therapeutic arthroscopies were performed, and typical localized PVNS was found. Complete resection of the lesions was performed arthroscopically. Arthroscopy can be used as an effective diagnostic and therapeutic tool for identification and treatment of intra-articular localized PVNS of the knee.

Adult↗
PubMed1998

Clinical courses of pure sleep epilepsies.

This study aims to understand seizure control outcomes and the risk of developing new wake seizures (WS) related to the different types of pure sleep epilepsies (SE), which is important in making rational management plans. A retrospective review of the Yonsei Epilepsy Clinic Registry identified 63 patients with pure SE not belonging to any specific epileptic syndromes. They were divided into the group of generalized tonic-clonic seizures during sleep (S-GTCS : n = 21) and the group of partial epilepsies during sleep (S-PE: n = 42) on the basis of seizure phenomenology, EEG, and neuroimaging data. These patients were followed for 2 years and their clinical variables were analysed for seizure control outcomes and development of new WS. Of 21 patients with S-GTCS, 17 achieved a seizure-free outcome and only one patient developed a new WS, which was consistent with a partial-onset secondary GTCS in phenomenology. Of 42 patients with S-PE only 15 patients achieved a seizure-free outcome and 11 patients developed WS during the 2-year follow-up period. Higher baseline seizure frequency and longer duration of epilepsy were associated with a higher incidence of new WS. The results suggest that the patients with S-GTCS carry a favorable clinical course, thus driving privileges or freedom of daily activities can be conferred without delay once their seizures are well controlled. However, the seizure control outcome was poor and the development of WS was frequent in patients with recurrent S-PE.

Adolescent↗
PubMed1998

The reverse digital artery island flap: clinical experience in 120 fingers.

Fingertip injuries represent the most common type of injuries seen in the upper extremity. Their management is functionally and aesthetically important but at the same time very controversial. The aim of this study is to report usefulness and postoperative results of reverse digital artery island flaps for fingertip reconstruction. From July of 1984 to December of 1995, 120 fingers in 110 patients with defects of the distal phalanx were reconstructed by reverse digital artery island flaps at Korea University Guro Hospital. We reviewed the medical records of our cases and analyzed them in several aspects. In 21 cases, neurorrhaphy was performed to improve sensibility. In the majority of the cases, the defect was covered primarily, whereas in 27 cases it was covered secondarily after composite graft, replantation, and so on. All the flaps survived except for one. Long-term follow-up for more than 6 months was possible in 44 fingers in 41 patients. Light touch and temperature sensation could be detected in all the evaluated flaps. The mean values of the static two-point discrimination test in sensate and insensate flaps were 6.2 and 10.2 mm, respectively. The reverse digital artery island flap is a safe and reliable procedure with a high survival rate and therefore is an excellent choice for coverage of fingertip defects.

Adolescent↗
PubMed1998

Ipsilateral thalamic hypoperfusion on interictal SPECT in temporal lobe epilepsy.

UNLABELLED: Interictal brain SPECT is useful for the localization of a seizure focus. Concomitant hypoperfusion of the ipsilateral thalamus on interictal SPECT has been noted for temporal lobe epilepsy. In this study, we aimed to evaluate the prevalence of thalamic hypoperfusion ipsilateral to temporal hypoperfusion (ipsilateral thalamic hypoperfusion) and to assess the usefulness of this finding for the lateralization of epileptic foci on interictal SPECT for temporal lobe epilepsy patients. METHODS: Forty-six patients with refractory temporal lobe epilepsy underwent interictal brain SPECT after intravenous injection of 555-740 MBq of 99mTc-ECD. Perfusion impairments in the brain, especially the temporal lobe and thalamus, were evaluated. The localization of seizure foci was determined in conjunction with scalp, ictal and cortical electroencephalography, MRI and clinical outcomes. Ictal SPECT was performed for 5 of the 12 patients. RESULTS: Concomitant decreased perfusion in both the temporal lobe and the ipsilateral thalamus was observed for 12 (26%) of 46 temporal lobe epilepsy patients on interictal brain SPECT. Seven patients showed hypoperfusion in the left temporal lobe and ipsilateral thalamus. Five patients showed hypoperfusion in the right temporal lobe and ipsilateral thalamus. In addition, hypoperfusion in the ipsilateral basal ganglia (ten patients) or contralateral cerebellum (four patients) was observed. CONCLUSION: Ipsilateral thalamic hypoperfusion is not uncommon in temporal lobe epilepsy. The exact mechanism causing ipsilateral thalamic hypoperfusion is uncertain; however, corticothalamic diaschisis may be an important factor. This finding may aid in the lateralization of seizure foci on interictal brain SPECT.

Adolescent↗
PubMed1997

Potential roles of osteopontin and alphaVbeta3 integrin in the development of coronary artery restenosis after angioplasty.

Angioplasty procedures are increasingly used to reestablish blood flow in blocked atherosclerotic coronary arteries. A serious complication of these procedures is reocclusion (restenosis), which occurs in 30-50% of patients. Migration of coronary artery smooth muscle cells (CASMCs) to the site of injury caused by angioplasty and subsequent proliferation are suggested mechanisms of reocclusion. Using both cultured human CASMCs and coronary atherectomy tissues, we studied the roles of osteopontin (OPN) and one of its receptors, alphavbeta3 integrin, in the pathogenesis of coronary restenosis. We also measured the plasma levels of OPN before and after angioplasty and determined the effect of exogenous OPN on CASMC migration, extracellular matrix invasion, and proliferation. We found that cultured CASMCs during log phase of growth and smooth muscle cell layer of the coronary atherosclerotic tissues of patients express both OPN mRNA and protein at a significantly elevated level compared with controls. Interestingly, whereas the baseline plasma OPN levels in control samples were virtually undetectable, those in patient plasma were remarkably high. We also found that interaction of OPN with alphavbeta3 integrin, expressed on CASMCs, causes migration, extracellular matrix invasion, and proliferation. These effects were abolished when OPN or alphavbeta3 integrin gene expression in CASMCs was inhibited by specific antisense S-oligonucleotide treatment or OPN-alphavbeta3 interaction was blocked by treatment of CASMCs with antibodies against OPN or alphavbeta3 integrin. Our results demonstrate that OPN and alphavbeta3 integrin play critical roles in regulating cellular functions deemed essential for restenosis. In addition, these results raise the possibility that transient inhibition of OPN gene expression or blocking of OPN-alphavbeta3 interaction may provide a therapeutic approach to preventing restenosis.

Adolescent↗