Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA microarray combined with laser microdissection: up-regulation of inflammation-associated STAT1, IRF1, CXCL9, CXCL10, and CCL5.

OBJECTIVES: The main histological change in rheumatoid arthritis (RA) is the villous proliferation of synovial lining cells, an important source of cytokines and chemokines, which are associated with inflammation. The aim of this study was to evaluate gene expression in the microdissected synovial lining cells of RA patients, using those of osteoarthritis (OA) patients as the control. METHODS: Samples were obtained during total joint replacement from 11 RA and five OA patients. Total RNA from the synovial lining cells was derived from selected specimens by laser microdissection (LMD) for subsequent cDNA microarray analysis. In addition, the expression of significant genes was confirmed immunohistochemically. RESULTS: The 14 519 genes detected by cDNA microarray were used to compare gene expression levels in synovial lining cells from RA with those from OA patients. Cluster analysis indicated that RA cells, including low- and high-expression subgroups, and OA cells were stored in two main clusters. The molecular activity of RA was statistically consistent with its clinical and histological activity. Expression levels of signal transducer and activator of transcription 1 (STAT1), interferon regulatory factor 1 (IRF1), and the chemokines CXCL9, CXCL10, and CCL5 were statistically significantly higher in the synovium of RA than in that of OA. Immunohistochemically, the lining synovium of RA, but not that of OA, clearly expressed STAT1, IRF1, and chemokines, as was seen in microarray analysis combined with LMD. CONCLUSIONS: Our findings indicate an important role for lining synovial cells in the inflammatory and proliferative processes of RA. Further understanding of the local signalling in structural components is important in rheumatology.

Interleukin-6-induced activation of signal transducer and activator of transcription-3 in ruptured rotator cuff tendon.

The aim of this study was to examine interleukin-6 production and the activation of signal transducer and activator of transcription-3 (STAT3) in ruptured rotator cuff tendon. Specimens of ruptured rotator cuff tendons were analysed using real-time reverse transcriptase polymerase chain reaction, Western blotting and immunohistochemistry. Specimens of co-existing inflammatory subacromial synovia were examined for comparison. The level of interleukin-6 messenger RNA was increased in ruptured rotator cuff tendon as well as in subacromial synovium. Western blot analysis showed constitutive production of activated, phosphorylated STAT3 in ruptured rotator cuff tendon and co-existing subacromial synovium. Immunohistochemical examination detected cells producing interleukin-6, interleukin-6 receptor and phosphorylated STAT3 in ruptured rotator cuff tendon, mainly in proliferative vessels and, to a lesser extent, in tendon fibroblasts around the vessels. This study demonstrates that activation of STAT3 induced by interleukin-6 is promoted mainly by proliferative vessels in ruptured rotator cuff tendon.

RETRACTED: Changes in the supporting muscles of the fractured hip in elderly women.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. The Journal has been made aware of concerns regarding the ethical approval for this study, and the study protocol and data were disputed. Since Dr Sato passed away, the co-authors were contacted about the complaint. Dr Izumi Kondo confirmed that the T score for sufficient 25OHD group in Table 2 was out of range and this was overlooked at the time of writing. He was unable to confirm whether the proper ethical approval was obtained or comment on the study protocol as his role was to advise on the statistical methodology of the revised paper. The other two co-authors did not respond, and one could not be located. This constitutes a violation of our publishing policies and publishing ethics standards.

Changes in bone and calcium metabolism following hip fracture in elderly patients.

Although hip fracture is one of the most common causes of acute immobilization in elderly patients, little is known about the influence of immobilization on changes in bone and calcium metabolism following this event. We therefore compared serum biochemical indices of bone and calcium metabolism in 20 elderly subjects with hip fracture with those measured in 20 healthy age-matched controls. Rankin scores, a measure of functional dependence with 0 representing independence and 5 representing total dependence, were assigned. We also examined serial changes in these biochemical indices from shortly following the fracture to the early recovery period. Ionized calcium, intact parathyroid hormone (PTH), intact bone Gla protein (BGP), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D (1,25-[OH]2D) were measured. One week after the fracture, mean serum concentrations of calcium and ICTP were elevated in correspondence to degree of immobilization (mean Rankin score; 4.4), while serum concentrations of BGP, PTH, 25-OHD, and 1,25-[OH]2D were depressed. Rankin score (mean: 4.4) correlated positively with ICTP and negatively with BGP at this time. At 2 months, calcium and ICTP elevation decreased and BGP, PTH and 1,25-[OH]2D were less depressed, coinciding with a decline in Rankin score from 4.2 to 2.2. Indices were further improved at 3 months (mean Rankin score, 1.3), with calcium and BGP returning to normal. We concluded that increased bone resorption, and decreased bone formation, and hypercalcemia are present by 1 week following the hip fracture, and some resorption increase persists for at least 3 months. These changes could explain in part the high risk of another hip fracture.

Reattachment of the greater trochanter using the Dall-Miles cable grip system in revision hip arthroplasty.

Clinical and radiographic results of trochanteric osteotomy after revision hip arthroplasty in 62 hips were reviewed. The osteotomized fragment had been reattached using the Dall-Miles cable grip system in each hip. The patients' average age at operation was 64.4 years (range, 40-86 years). The average duration of follow-up was 30.0 months (range. 12-60 months). Trochanteric nonunion was found in 19 hips (30.6%). Trochanteric nonunion developed in 14 (38.9%) of 36 hips with each cable attached around the medial cortex bone, in 2 (16.7%) of 12 hips with each cable passed in a drill hole, and in 3 (21.4%) of 14 hips with one cable passed through a hole and the other attached around the medial cortex. Fragmentation developed in 18 hips (29.0%). In 3 of these 18, the fragments had migrated close to the acetabular component. Cable breakage was seen in 4 hips (6.5%), and bone absorption around the cable in the medial cortex was seen in 17 hips (27.4%). There were 16 hips (25.8%) that presented symptoms at the greater trochanter, including spontaneous pain and tenderness. When the Dall Miles cable grip device is used for reattachment of the greater trochanter, attention should be paid to the condition of the trochanteric bed, the tension of the abductor muscles, and to the placement of the cables and the H-shaped grip.

Biomechanical study of the resurfacing hip arthroplasty: finite element analysis of the femoral component.

Finite element analysis was performed using 3-dimensional models to examine the biomechanical characteristics of the femoral component in resurfacing hip arthroplasty. Stress concentration was observed in the cortical bone adjacent to the rim of the prosthesis. Stress shielding was observed in the anterosuperior regions on the cancellous bone cross-sections near the cup rim. These biomechanical characteristics may lead to complications such as femoral neck fractures in patients with osteopenic bone and long-term loosening.

Joint-preserving operation for osteoarthrosis of the hip in adult cerebral palsy.

BACKGROUND: A joint-preserving operation was performed on 15 hips with osteoarthrosis, involving 12 patients who had adult cerebral palsy. METHODS: Eleven hips underwent Chiari pelvic osteotomy only; three hips underwent Chiari pelvic osteotomy with femoral osteotomy and the other one hip underwent femoral varus osteotomy only. The mean follow-up period after surgery was 6 years and 2 months (with follow-up range of 2 years and 3 months to 10 years and 6 months). RESULTS: Good results were achieved in 13 of the 15 hips (86.6%). Two patients with athetotic tetraplegia treated with Chiari pelvic osteotomy had pelvic obliquity. Progressive osteoarthrotic change continued in bilateral hips in one case treated with Chiari pelvic osteotomy. CONCLUSION: We confirm that usual treatment for osteoarthrosis of the hip was also applicable for osteoarthrosis of the hip in cases of adult cerebral palsy, provided sufficient attention is given to the complications accompanying spastic paralysis.

Biomechanical effect and clinical application of the hip joint moment reduction brace.

A new brace, the hip joint moment reduction brace, has been designed and constructed. The basic construct of the brace incorporates only the thigh, and it minimally restricts one's activities of daily living. The concept of the brace is to reduce the frontal plane moment of the applied force against which the abductor muscle must contract to balance, and this reduction of the frontal plane moment results in reduction of the abductor muscle force. The brace uses the mechanism of the ischial weightbearing and lessens the abductor moment by transmitting load from the ischium through the condyle of the femur. In gait testing, the maximum ischial load taken up by the brace was 36.9% of the ground reaction force in the late stance phase, and the integrated electromyogram of the abductor muscle was reduced by 32.6% during the whole stance phase using this brace. These findings confirmed a reduction in the frontal plane moment of the hip joint and the potential for reduction in the load on the hip joint. The hip joint moment reduction brace is recommended as effective conservative management of hip disorders, such as coxarthrosis, that are caused or worsened by biomechanical insufficiency.

Modified Chiari osteotomy for arthrosis after Perthes' disease. 14 hips followed for 2-12 years.

Between 1983 and 1995, a modified Chiari pelvic osteotomy was performed for coxarthrosis after Perthes' disease in 13 patients (14 hips). The median age at operation was 33 (16-56) years. The median duration of follow-up was 6 (2-12) years. The center-edge angle, Sharp's angle, acetabulum head index and acetabular edge angle improved substantially. The median hip score substantially improved from 76 (46-90) points to 91 (71-100) points at the most recent follow-up examination. We recommend this procedure for patients who have early arthrosis, acetabular dysplasia, pain and good range of motion.

Metal-on-metal CoCrMo McKee-Farrar total hip arthroplasty: characteristics from a long-term follow-up study.

A total of 38 cemented metal-on-metal CoCrMo McKee-Farrar total hip arthroplasties (THAs) were clinically and radiographically evaluated over a long-term follow-up. No osteolysis and no granuloma were found more than 20 years after the operation. The main radiological findings were bone erosion and migration of the acetabular component, seen in 17 hips (44.7%). The direction of the migration correlated with the setting position of the acetabular component at operation. At revision surgery, metallosis was observed in unstable THA, and no metallosis was observed in stable THA. Using a micrometer, no wear of the sockets was found. Therefore, the loosening was thought to be due to the equatorial bearing rather than to metallosis. The mean survival of the THA to data was 14.6 years in those patients 60 years old or younger at operation and was significantly less (11.9 years) in those 61 years old or older at operation (P < 0.03). The mean survival time was 13.8 years.

Application of Dall-Miles cable grip system for transtrochanteric osteotomy.

We have applied the Dall-Miles cable grip system for fixation in 15 cases of a transtrochanteric valgus osteotomy for osteoarthritis. After three phases of modification, we could achieve stable fixation for the three fragments of the greater trochanter, proximal and distal femur using only one set of this system and could prevent migration and over-traction of the abductor muscles by this way.

Functional evaluation of hip abductor muscles with use of magnetic resonance imaging.

The hip abductor muscles are considered important for gait and biomechanics of the hip joint; however, their specific function has not been defined precisely. The intensity of magnetic resonance imaging signals in skeletal muscle has been reported to increase immediately after exercise. Making use of this phenomenon, we evaluated the hip abductor muscles. Magnetic resonance imaging was performed after isometric exercise of the hip abductor in three positions (20 degrees of abduction, neutral, and 20 degrees of adduction). The abduction force of the hip was measured with a dynamometer, and electromyographic measurements were made simultaneously for the same hip positions. Additionally, magnetic resonance imaging was performed after one-legged stance. As the hip was more adducted, the signal intensity increased on the scans. The values for muscle force, as evaluated with the dynamometer and integrated electromyography, also supported the results. The increase in signal intensity of the gluteus minimus at 20 degrees of abduction and after one-legged stance was significantly greater than that of the gluteus medius (p < 0.0001 and p < 0.0001, respectively). The results of this study indicate that the gluteus minimus muscle, along with the gluteus medius, plays an important role in hip abduction, gait, and stabilization of the pelvis.

Flushing pattern and idiopathic avascular necrosis of the femoral head.

A cooperative hospital-based case-control study of idiopathic avascular necrosis of the femoral head (IANF) was carried out to clarify the involvement of smoking, drinking, flushing pattern, and other factors in the development of IANF comparing 90 cases (64 males and 26 females) without history of systemic corticosteroid use with 180 matched controls (128 males and 52 females). The results of analyses were represented only for male subjects because of small number of female cases. There was no significant difference in smoking habits, daily and cumulative number of cigarettes smoked between case and control groups. Current drinkers had obviously higher risk (OR = 11.47) of IANF compared to nondrinkers or exdrinkers. In addition, there was a consistent risk increase with increasing alcohol consumption and the highly significant dose-response relationship remained unchanged after adjustment for all other factors (chi 2 = 14.33, p < 0.001 and chi 2 = 13.24, p < 0.001 for daily and cumulative alcohol consumption, respectively). For flushing pattern, although nonflushers had a significantly elevated risk (OR = 2.08) in the univariate analysis, the association disappeared (OR = 0.73) after adjustment for alcohol and other factors. Since nonflushers tend to be heavy drinkers, perhaps, an apparent risk increase among nonflushers may be due to alcohol drinking. Body mass index (BMI) was inversely related to the development of IANF. The risk reduction was found among subjects with higher BMI and an adjusted linear trend of OR was significant (chi 2 = 6.65, p < 0.05). However, further studies were required regarding the association between flushing pattern or BMI and IANF because of a few reports. History of liver diseases and occupational history were not significantly associated with the development of IANF after adjustment for other factors.

Fracture of an alumina ceramic head in total hip arthroplasty.

The authors have experienced a fracture in the ceramic head in a total hip arthroplasty in three cases. Two of these were comminuted and the other was a hair-line fissure. A foreign body, perhaps from the operation, existed between the neck of the stem and the head in two cases (one in a comminuted fracture and the other in the fissure fracture). The other case had no foreign body, and, judging from the serial radiographs, the fracture was probably caused by weight-bearing stress. Care must be taken during operation to avoid interposing any foreign body in the modular ceramic head total hip arthroplasty, and the weight-bearing stress factor must be considered as an indication for a ceramic head fracture in young active patients.

Release of lidocaine from polymer film dosage forms.

We investigated the in vitro drug release from mixed polymer films using lidocaine (LC), which is poorly water-soluble. The mixed polymer films consisted of various ratios of hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose phthalate (HPMCP). The effects of the presence glycyrrhizic acid (GL) or polyethylene glycol (PEG) in the films upon LC release were also studied. LC crystallinity decreased in the polymer film and this decrease was remarkable in the presence of GL, resulting in an amorphous state. During the initial stage, drug release was regarded as a zero-order dissolution. The apparent release rate constant, ka, varied with the ratios of the two polymers and the amount of additives as well as with the pH of the test solution. The results indicated that GL enhanced the dissolution rate of LC from mixed polymer films, which may be due to the formation of an amorphous state. On the other hand, since PEG is a surfactant, the enhanced wettability of the polymer by the buffered solutions may have caused the increased dissolution rate.

Adult idiopathic chondrolysis of the hip--report of two cases.

Idiopathic chondrolysis of the hip is characterized by pain, limping and a progressive restriction in the range of motion of the hip. The paper describes the case of two female patients, age 28 and 37, who were referred to our hospital in October 1985 and May 1991 for pain and limitation of movement in the right hip. Neither patient had a previous history of systemic illness or trauma or medication such as steroids. On admission they underwent clinical and X-ray examinations. Both required an open biopsy to confirm the diagnosis. They have been followed for 4 years and 8 years, respectively.

Ellagic acid/phospholipid-induced coagulation and dextran sulfate-induced fibrinolytic activities in beta 2-glycoprotein I-depleted plasma.

Beta 2-glycoprotein I (beta 2-GPI) binds negatively charged substances and inhibits intrinsic blood coagulation in the presence of ellagic acid-phospholipid suspension. Beta 2-GPI is thought to be an important protein in the reaction between negatively charged phospholipids and anti-phospholipid antibodies which appear in patients with lupus anticoagulant/antiphospholipid antibody syndrome. We prepared a monoclonal antibody against beta 2-GPI purified from human plasma and obtained beta 2-GPI-depleted plasma using a monoclonal antibody-coupled column. Either partial thromboplastin time or the activation of prekallikrein induced by diluted ellagic acid-phospholipid suspension in beta 2-GPI-depleted plasma was not different from that in control plasma. Beta 2-GPI inhibited the intrinsic blood coagulation only when added to control or beta 2-GPI-depleted plasma in excess (more than physiological concentrations). The intrinsic fibrinolysis in beta 2-GPI-depleted plasma induced by dextran sulfate was not impaired and, again, beta 2-GPI inhibited the intrinsic fibrinolysis only when added to control or beta 2-GPI-depleted plasma in excess. These results indicate that both in vitro Actin-induced intrinsic coagulation and dextran sulfate-induced fibrinolytic activities are significantly inhibited by more than physiological concentrations of beta 2-GPI.

Changes in the interposed capsule after Chiari osteotomy. An experimental study on rabbits with acetabular dysplasia.

We have investigated the changes in the interposed capsule after a Chiari pelvic osteotomy, in an experimental study on dysplastic hips in 20 adolescent rabbits. Radiographic, macroscopic and microscopic observations were made up to 12 months after operation. The new acetabular roof had incorporated the interposed capsule and remodelled completely by six months. By 12 months there was a new, stable hip with continuity between the capsule and the original acetabular cartilage. Histologically, the capsule underwent metaplastic change to fibrocartilaginous tissue after six months, with some hyaline-like cartilage near the joint surface. These changes in the interposed capsule play an important role in the formation of a new joint after a Chiari pelvic osteotomy.

Characterization of flat revertants isolated from cells transformed by Abelson murine leukemia virus (Ab-MuLV).

Transformed Fisher rat fibroblast cell lines by Abelson murine leukemia virus frequently revert to the normal phenotype in usual culture conditions. Molecular biological analysis of three revertant clones isolated from the transformants showed that their morphological reversions were due to inactivation of the v-abl oncogene at multiple steps including transcription, translation or v-abl protein kinase activity itself without any change in structural gene expression of helper virus. These findings suggest the existence of a specific mechanism(s) for elimination of the v-abl oncogene by segregation, mutation, or gene rearrangement in these cells.

An improved method for the detection of HIV antigen in the blood of carriers.

The measurement of HIV antigen levels in sera or plasma of HIV-infected individuals is critical for determining the existence of antigen or infectious virus before seroconversion and for prognosis. Pretreatment of sera or plasma of HIV carriers by heating at 70 degrees C for 10 min at an acidic pH enabled us to estimate antigens efficiently in immune complexes. This procedure will also be useful in determining antigen levels in HIV carriers more precisely.