Controlling joint instability after anterior cruciate ligament transection inhibits transforming growth factor-beta-mediated osteophyte formation.

OBJECTIVE: Abnormal joint instability contributes to cartilage damage and osteophyte formation. We investigated whether controlling joint instability inhibited chronic synovial membrane inflammation and delayed osteophyte formation and examined the role of transforming growth factor-beta (TGF-ß) signaling in the associated mechanism. DESIGN: Rats (n = 94) underwent anterior cruciate ligament (ACL) transection. Anterior tibial instability was either controlled (CAM group) or allowed to continue (SHAM group). At 2, 4, and 8 weeks after surgery, radiologic, histopathologic, immunohistochemical, immunofluorescent, and enzyme-linked immunosorbent assay examinations were performed to evaluate osteophyte formation and TGF-ß signaling. RESULTS: Joint instability increased cartilage degeneration score and osteophyte formation, and cell hyperplasia and proliferation and synovial thickening were observed in the synovial membrane. Major findings were increased TGF-ß expression and Smad2/3 following TGF-ß phosphorylation in synovial membarene, articular cartilage, and the posterior tibial growth plate (TGF-ß expression using ELISA: 4 weeks; P = 0.009, 95% CI [260.1-1340.0]) (p-Smad2/3 expression density: 4 weeks; P = 0.024, 95% CI [1.67-18.27], 8 weeks; P = 0.034, 95% CI [1.25-25.34]). However, bone morphogenetic protein (BMP)-2 and Smad1/5/8 levels were not difference between the SHAM model and the CAM model. CONCLUSIONS: This study showed that the difference between anterior tibial instability caused a change in the expression level of TGF in the posterior tibia and synovial membrane, and the reaction might be consequently involved in osteophyte formation.

Controlling joint instability delays the degeneration of articular cartilage in a rat model.

OBJECTIVE: Joint instability induced by anterior cruciate ligament (ACL) transection is commonly considered as a predisposing factor for osteoarthritis (OA) of the knee; however, the influence of re-stabilization on the protection of articular cartilage is unclear. The aim of this study was to evaluate the effect of joint re-stabilization on articular cartilage using an instability and re-stabilization ACL transection model. DESIGN: To induce different models of joint instability, our laboratory created a controlled abnormal joint movement (CAJM) group and an anterior cruciate ligament transection group (ACL-T). Seventy-five Wistar male rats were randomly assigned to the CAJM (n = 30), ACL-T (n = 30), or no treatment (INTACT) group (n = 15). Cartilage changes were assessed with soft X-ray analysis, histological and immunohistochemistry analysis, and real-time polymerase chain reaction (PCR) analysis at 2, 4, and 12 weeks. RESULTS: Joint instability, as indicated by the difference in anterior displacement between the CAJM and ACL-T groups (P < 0.001), and cartilage degeneration, as evaluated according to the Osteoarthritis Research Society International (OARSI) score, were significantly higher in the ACL-T group than the CAJM group at 12 weeks (P < 0.001). Moreover, joint re-stabilization maintained cartilage structure (thickness [P < 0.001], surface roughness [P < 0.001], and glycosaminoglycan stainability [P < 0.001]) and suppressed tumor necrosis factor-alpha (TNF-α) and caspase-3 at 4 weeks after surgery. CONCLUSION: Re-stabilization of joint instability may suppress inflammatory cytokines, thereby delaying the progression of OA. Joint instability is a substantial contributor to cartilage degeneration.

Chiral magnetic soliton lattice on a chiral helimagnet.

Using Lorenz microscopy and small-angle electron diffraction, we directly present that the chiral magnetic soliton lattice (CSL) continuously evolves from a chiral helimagnetic structure in small magnetic fields in Cr(1/3)NbS2. An incommensurate CSL undergoes a phase transition to a commensurate ferromagnetic state at the critical field strength. The period of a CSL, which exerts an effective potential for itinerant spins, is tuned by simply changing the field strength. Chiral magnetic orders observed do not exhibit any structural dislocation, indicating their high stability and robustness in Cr(1/3)NbS2.

Electron microscopy at a sub-50 pm resolution.

An aberration-corrected electron microscope developed in CREST project has been applied for imaging atoms and clusters buried inside crystals. The resolution of the microscope in scanning transmission electron microscopy (STEM) has experimentally proved to be better than 47 pm by use of a cold-field emission gun at 300 kV. The high resolution has given an advantage for imaging light elements such as lithium atoms discriminating one by one. Moreover, a three-dimensional structure imaging has been demonstrated for dopant clusters by a sub-50 pm STEM, using its high depth resolution.

Effect of position of electrodes relative to the innervation zone onsurface EMG.

We investigated the effect of the position of electrodes relative to the innervation zone (IZ) of the biceps brachii muscle during isometric elbow flexion using eight-channel surface array electrodes. We estimated the location of the IZ near the centre of the muscle in 20 male subjects. The pulse peaks from electromyogram (EMG) waveforms were detected for each channel and averaged, the triphasic pulse was determined, and the peak values of the first and third phases were compared. The results showed significantly greater pulse values for the first phase when the electrode placement was proximal to the estimated IZ, and for the third phase when the electrode placement was distal to the estimated IZ. Using this method, the positional relationship between electrodes and IZ can be determined using a surface EMG waveform recorded with a pair of bipolar electrodes. This method may be clinically useful in confirming the reliability of a recorded surface EMG.

Contrasting alteration patterns of different cartilage plates in knee articular cartilage after spinal cord injury in rats.

STUDY DESIGN: Experimental, controlled trial, animal study. OBJECTIVE: To assess morphologic changes in different cartilage plates after spinal cord injury and identify the localization of these alterations. SETTING: Saitama, Japan. METHODS: A total of 16 Wistar rats were used. Eight rats underwent a spinal cord injury and eight rats had no intervention as control. The cartilage alterations of the knee joint were evaluated with radiography and histomorphometric analysis. To quantify cartilage alterations, we selected the histologic characteristics: thickness of the articular cartilage, number of chondrocytes, matrix staining to toluidine blue as a reflection of proteoglycan content and surface irregularity. RESULTS: No differences in knee joints were found between the groups by radiography. In the medial knee joint, cartilage thickness of spinal-cord-injured knees increased at the anterior femoral region and decreased at the tibial and posterior femoral regions; however, in the lateral knee, that of spinal cord injuries did not change compared with control knees. Spinal cord injuries decreased the number of chondrocytes, especially at the anterior femoral regions. Matrix staining increased partially at the tibial regions. Surface irregularity of spinal-cord-injured knees was comparable to that of control knees in all cartilage plates. CONCLUSION: The present findings exhibit characteristics of the cartilage after spinal cord injury. These alterations were different in nature between the medial and lateral regions. Future studies should assess separately different cartilage plates, to overestimate these severities when the changes at the medial knee were examined and to underestimate when the changes at the lateral knee were examined.

Measurement method of aberration from Ronchigram by autocorrelation function.

Aberrations up to the fifth-order were successfully measured using an autocorrelation function of the segmental areas of a Ronchigram. The method applied to aberration measurement in a newly developed 300kV microscope that is equipped with a spherical aberration corrector for probe-forming systems. The experimental Ronchigram agreed well with the simulated Ronchigram that was calculated by using the measured aberrations. The Ronchigram had an infinite magnification area with a half-angle of 50mrad, corresponding to the convergence angle of a uniform phase.

Alteration in articular cartilage of rat knee joints after spinal cord injury.

OBJECTIVE: Mechanical forces are crucial for the maintenance of the morphologic and functional integrity of articular cartilage. The alteration of the articular cartilage after spinal cord injury (SCI) has been described in relation to a suppression of mechanical forces, since the joint is unloaded and restricted in movement. However, the morphological and biochemical characteristics of the cartilage after SCI are still poorly understood. We identified the localization of cartilage alterations after SCI and verified the influence of mechanical forces on the articular cartilage. METHOD: A total of 32 Wistar rats were used. Sixteen animals underwent an SCI and 16 animals served as control. The articular cartilage of the knee joint was assessed, respectively, at 4, 8, 10, and 12 weeks after intervention by histochemical, histomorphometric, immunohistochemical, and biochemical analyses. RESULTS: Cartilage thickness of spinal cord-injured knees decreased at the tibial and posterior femoral (FP) regions and increased at the anterior femoral (FA) region. Spinal cord injuries decreased the number of chondrocytes at the anterior regions and decreased the cartilage matrix staining only at the tibial regions. Immunolabeling to collagen type II was noted comparably in the superficial layer but noted weakly from the middle to deep layer. Collagen type I existed excessively at the cartilage surface and the pericellular regions. CONCLUSION: Cartilage alterations after SCI would not be explained by only a suppression of mechanical forces by unloading and immobilization, but there may be influences on the cartilage in addition to the change in mechanical forces.

Allele frequencies of the six miniSTR loci in a population from Japan.

Allele frequencies and forensic parameters for the six miniSTR loci D1S1677, D2S441, D4S2364, D10S1248, D14S1434, and D22S1045 were investigated in a sample of 142 unrelated healthy Japanese individuals. The polymerase chain reaction (PCR) products contained within the six loci were less than 119 bp in size. The frequency distributions in the six short tandem repeat (STR) loci showed no deviations from Hardy-Weinberg equilibrium expectations. The accumulated powers of discrimination and power of exclusion for the six loci were 0.999998 and 0.98, respectively. It was thus considered that due to the small PCR products and the moderate degree of polymorphism, analysis with use of the six miniSTR loci was highly beneficial for the forensic analysis of degraded DNA.

Remnant-like lipoprotein particles as risk factors for coronary artery disease in elderly patients.

Although remnant-like lipoprotein particles (RLPs) are known to be atherogenic, the relationship between serum RLP-cholesterol (RLP-C) level and coronary artery disease (CAD) has not as yet been evaluated. This clinical study was aimed at investigating the pathological significance of serum RLP-C among several coronary risk factors with a clear focus on elderly patients. We took fasting venous blood samples to determine lipid profiles including RLP-C from 188 patients with angiographically identified CAD and 68 control patients. Overall analysis showed that the RLP-C/HDL-C ratio was higher in both single-vessel CAD group (n = 67; p < 0.01) and multi-vessel CAD group (n = 121; p < 0.001) compared to controls. Further, multiple logistic regression analysis indicated that the diabetes, HDL-C and the RLP-C/HDL-C ratio could discriminate CAD patients from controls. In patients younger than 65 years, diabetes, HDL-C, LDL-C and the LDL-C/HDL-C ratio as well as the RLP-C/HDL-C ratio could discriminate CAD. In patients 65 aged years or older, however, diabetes, triglyceride and RLP-C as well as the RLP-C/HDL-C ratio could discriminate CAD, whereas LDL-C and the LDL-C/HDL-C ratio could not. These results led us to believe that the contribution of a given risk factor to the development of CAD in elderly patients may be different from that in younger patients. In elderly patients, RLP-C rather than LDL-C was strongly associated with the development of CAD. Accordingly, serum RLP-C levels may serve as a convenient and reliable index for assessing CAD.

Acute myocardial infarction associated with myocardial bridge and coronary artery vasospasm.

A 65-year-old man was admitted to our hospital with acute myocardial infarction (MI). Emergency coronary angiography showed no significant organic lesions, but a myocardial bridge was found at the mid-left anterior descending artery An acetylcholine provocation test revealed 90% spastic stenosis just proximal to the myocardial bridge. His acute MI could have been caused by both a coronary spasm and the myocardial bridge.

Molecular genetic analysis of the Am phenotype of the ABO blood group system.

BACKGROUND AND OBJECTIVES: Many sequences of variants in the ABO blood group system have been analysed, but genetic information is not available on the rare Am phenotype blood group. We isolated the Am phenotype in one family and performed molecular analysis on this allele. MATERIALS AND METHODS: Exons 6 and 7 of the ABO gene were analysed using genomic DNAs from members of one family containing Am phenotype individuals via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. RESULTS: In the Am allele, two single base substitutions were detected compared with the A101 allele. Both were C --> T mutations at nucleotide positions 467 and 761. PCR-RFLP using the AccI restriction enzyme was performed to detect the Am allele in 214 samples that had already been determined as type A or O by serological tests, but no sample was found to contain an Am allele. CONCLUSIONS: In this study a new allele with a single-base substitution at nucleotide position 761 was identified in the Am phenotype. We designated this new allele as A112 (according to the guidelines for human gene nomenclature) and determined that PCR-RFLP analysis using the AccI restriction enzyme will be useful for detecting this allele.

Population pharmacokinetics of tacrolimus in adult recipients receiving living-donor liver transplantation.

OBJECTIVE: To characterize the pharmacokinetics of tacrolimus in adult recipients receiving living-donor liver transplantation (LDLT). METHODS: Thirty-five patients were given tacrolimus as 18- to 60-h intravenous infusions after surgery, followed by a 4-week course of oral dose therapy (at 0900 hours and 2100 hours). Blood samples were collected daily in the morning (0800 hours) beginning the day after surgery. Whole blood concentration data were evaluated by nonlinear mixed-effect modeling using the program NONMEM and were characterized using a one-compartment model. RESULTS: The clearance (CL, l h(-1)) was related to the grafted hepatic weight, postoperative days (POD), and hepatic and renal dysfunction. Interindividual variabilities in CL, volume of distribution (V), and bioavailability (F) were 57.4%. 39.7%, and 63.0%, respectively, and the correlation between individual CL and F was 0.776. Residual intraindividual variability was 2.9 ng ml(-1). Based on the estimated final parameters, a typical recipient of LDLT with grafted hepatic weight of 600 g and normal hepatic and renal function would have a CL of 0.737 l h(-1) on POD 0 and 1.14 l h(-1) on POD 30, V of 1.52 l kg(-1) and F of 6.8%. CONCLUSIONS: Nonlinear mixed-effect modeling was useful for analysis of pharmacokinetic characteristics of tacrolimus in LDLT patients. Immediately after surgery, patients receiving LDLT showed a smaller CL value than other transplant patients, and CL value increased with POD within 30 days after surgery. The estimated population pharmacokinetic parameters can be applied for a priori dosage calculations in adult patients with LDLT.

Clinical significance of antibody against oxidized low density lipoprotein in patients with atherosclerotic coronary artery disease.

OBJECTIVES: This study was designed to establish the clinical significance of antibodies against oxidized low density lipoprotein (anti-Ox-LDL) titer in atherosclerotic coronary artery disease (CAD). BACKGROUND: Oxidative modification of LDL, which plays a key role in the development of atherosclerosis, induces immunogenic epitopes in the LDL molecule, and the presence of anti-Ox-LDL has been demonstrated in human sera. METHODS: Anti-Ox-LDL titer was measured by enzyme-linked immunosorbent assay in 108 patients who had angiographically verified CAD, and 31 patients who had chest pain but no significant CAD, as controls. RESULTS: The anti-Ox-LDL titer was higher (p < 0.01) in patients with multivessel CAD (19.4 +/- 10.1 AcU/ml, n = 68) than in the controls (9.8 +/- 4.1). However, no significant difference was shown between the single-vessel CAD group (15.1 +/- 6.4, n = 40) and the controls, or between the multivessel CAD group and the single-vessel CAD group. The titer was higher in patients with unstable angina (21.5 +/- 11.8 AcU/ml, n = 20, p < 0.01), or in patients with acute myocardial infarction (23.1 +/- 12.0, n = 20, p < 0.01) than in patients with stable-effort angina or old myocardial infarction (12.2 +/- 8.6, n = 68). Multiple logistic regression analysis indicated that the anti-Ox-LDL titer most powerfully discriminated CAD patients from controls (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.07-1.33, p = 0.0006) and acute coronary syndrome from chronic CAD (OR: 1.09, 95% CI: 1.04-1.14, p = 0.0008). CONCLUSIONS: Serum anti-Ox-LDL titer not only can predict a presence of atherosclerotic CAD but also may be a marker of plaque instability. Low density lipoprotein oxidation may play an important role in the development of plaque instability.

Significance of platelet aggregability immediately after blood sampling and effect of cigarette smoking.

A novel type platelet aggregometer, a WBA Analyzer, has enabled us to obtain the platelet aggregability data immediately after blood sampling, which is considered to closely reflect in vivo platelet function. Using this analyzer, we measured the platelet aggregatory threshold index (PATI) 5 min after blood sampling and compared it with that 60 min after blood sampling in 20 healthy male volunteers (10 smokers and 10 non-smokers). In the non-smokers, PATI was 10.3+/-2.3 microM 5 min after blood sampling, and it decreased to 4.7+/-1.5 (P<0.001) 60 min after blood sampling. In the smokers, the PATI was 7.7+/-2.9 microM 5 min after blood sampling, and it decreased to 3.8+/-1.5 (P<0.001) at 60 min after blood sampling. In the smokers, the PATI 5 min after blood sampling increased after a 4-week cessation of smoking (10.4+/-2.9, P<0.01), although the PATI 60 min after blood sampling did not change (4.2+/-1.6 microM). The measurement of platelet aggregability immediately after blood sampling using a WBA Analyser may be useful to evaluate not only platelet function in various thrombotic disorders, but also the effects of various anti-platelet drugs. Cessation of smoking should also be encouraged in the light of the adverse effects on platelet function.

Unusual coronary artery aneurysm and acute myocardial infarction in a middle-aged man with systemic lupus erythematosus.

A 55-year-old man developed acute myocardial infarction (AMI) related to a large coronary artery aneurysm and a distal coronary stenotic lesion after steroid therapy for systemic lupus erythematosus (SLE). Only 13 SLE patients with AMI caused by coronary artery aneurysms have been reported, 11 of whom were young or middle-aged women and the 2 remaining were young men. This is the first report of a middle-aged man with multiple coronary lesions.

Using cineradiography for continuous dynamic-motion analysis of the lumbar spine.

STUDY DESIGN: Cineradiography was used to analyze continuous dynamic motion in the lumbar spine. OBJECTIVES: To identify motion patterns of the lumbar spine in asymptomatic volunteers and symptomatic patients with L4 degenerative spondylolisthesis, and to use the findings to discuss segmental instability in this disorder. SUMMARY OF BACKGROUND DATA: The use of radiographic findings to assess lumbar spine instability remains controversial. Although some studies have reported on lumbar kinematics during actual movement, the motion patterns in asymptomatic volunteers and symptomatic patients with L4 degenerative spondylolisthesis have not been fully clarified. METHODS: While asymptomatic volunteers (n=20; mean age, 27; control group) and symptomatic patients with L4 degenerative spondylolisthesis (n=41; mean age, 63; degenerative spondylolisthesis [DS] group) flexed from a sitting neutral position and back to the neutral position (flexion course), cineradiography was used to record lateral segmental lumbar motions. Twelve frames were selected during the flexion course, and flexion-extension angle (f-e angle) and translation in the sagittal plane were measured at each motion segment (L2-L3, L3-L4, L4-L5, and L5-S1). The DS group was classified into 2 subgroups according to percentage of slip: DS group I, with a slip equal to or less than 15%; and DS group II, with a slip of more than 15%. The motion pattern was compared between the groups. RESULTS: In the control group, f-e angle and translation at the L2-L3, L3-L4, and L4-L5 segments moved simultaneously, although the L5-S1 segment showed an initial delay. The amount of f-e angle and translation changed almost symmetrically. In both f-e angle and translation, the L4-L5 segment showed a large motion pattern. In DS group I (n=21), the L4-L5 segment showed a large motion pattern in f-e angle and an intermediate motion pattern in translation. In DS group II (n=20), the L4-L5 segment showed an intermediate motion pattern in f-e angle, and a small motion pattern in translation. The relative range of f-e angle at the L4-L5 segment had the largest range in DS group I, and the relative translation showed a serial decrease from the control group through DS group II. A significant correlation between f-e angle and translation (harmonious motion pattern) was noted at the L2-L3, L3-L4, and L4-L5 segments in the control group. The harmonious motion pattern at the L4-L5 segment was significantly less in the DS group than in the control group. The loss of harmonious motion pattern (disordered motion pattern) at L4-L5 was well-revealed in the DS group II. CONCLUSIONS: Motion analyses using cineradiography helped to explain the phenomena of lumbar spine kinematics. Based on continuous dynamic-motion analysis with cineradiography, large f-e angle and disordered motion pattern during the flexion-backward course in the DS group I was considered to be caused by segmental instability. The decreased translation and disordered motion pattern throughout the flexion course in the DS group II was considered to be caused by restabilization.

Skew deviation as a complication of cardiac catheterization.

PURPOSE: To report three patients who developed diplopia and skew deviation after cardiac catheterization. DESIGN: Interventional case series. METHODS: Three patients complained of diplopia after cardiac catheterization for myocardial infarction (two male patients) or aortic dissection (one female patient). Examination demonstrated skew deviation in each patient. RESULTS: Diplopia and skew deviation were mild and resolved completely in 4 months (case 1), 16 months (case 2), and 1.5 months (case 3). Sensitive signs of minor ischemic damage to the brain stem that cause such disorders are not detectable by neuroimaging. CONCLUSION: Rarely, cardiac catheterization may be complicated by diplopia and skew deviation.

Quantitative high-resolution microscopy on a suspended chain of gold atoms.

High-resolution electron microscope images of a suspended gold chain were analyzed quantitatively. The images of the suspended gold chain were recorded on videotapes, during in situ observation in an ultra-high-vacuum electron microscope. The chain consisted of four gold atoms free from any substrate. Image simulation verified that the gold chain has a center-top geometry. The simulation also showed that the chain has no glue atoms spinning around the axis of the chain. A spinning gold atom was shown to give 50% of the stationary atom in gray scale. By comparing the noise level of the observed image and the gray scale of single atoms such as C, Si, S, Cu, and Au, we verified that the Si and S atoms have almost twice as large contrast as the noise (peak-to-peak), and C atoms have almost the same contrast as the noise level. The analysis showed it critical to detect a single Si and S atoms.

Antibody against oxidized low density lipoprotein may predict progression or regression of atherosclerotic coronary artery disease.

OBJECTIVES: This study aimed to elucidate whether an antibody against oxidized low density lipoprotein (anti-Ox-LDL) could predict short-term coronary artery atherosclerotic lesion progression. BACKGROUND: It is still controversial whether higher levels of the anti-Ox-LDL titer are associated with atherosclerotic coronary artery disease. METHODS: In 52 patients undergoing coronary angioplasty and six-month follow-up angiography, we performed quantitative coronary angiographic analysis of a lesion on a branch away from the intervention site vessel and assessed lesion progression or regression using the Progression-Regression score calculated as the baseline minimal lumen diameter minus the follow-up minimal lumen diameter. The serum anti-Ox-LDL titer was measured using an enzyme-linked immunosorbent assay method just before the initial angiography in all patients. RESULTS: The anti-Ox-LDL titer was 16.6+/-1.5 AcU/ml in the progression group (Progression-Regression score >0.15 mm; n = 20), which was significantly higher (p < 0.001) than the value of 9.5+/-1.2 in the regression group (< or =-0.15 mm; n = 14) and also higher (p < 0.01) than the value of 11.4+/-1.3 in the no-change group (-0.15 to 0.15 mm; n = 18). The Progression-Regression score was correlated with the antibody titer in all patients (r = 0.56, p < 0.001). Multiple regression analysis showed that the Progression-Regression score was independently correlated with the antibody titer (r = 0.44, p < 0.01) as well as lipoprotein (a) (r = 0.33, p < 0.05). CONCLUSIONS: Anti-Ox-LDL may be an independent predictor of coronary atherosclerotic lesion progression in the short term.