New evidence for the Ontong Java Nui hypothesis.

The formation of the Ontong Java Nui super oceanic plateau (OJN), which is based on the model that the submarine Ontong Java Plateau (OJP), Manihiki Plateau (MP), and Hikurangi Plateau (HP) were once its contiguous fragments, could have been the largest globally consequential volcanic event in Earth's history. This OJN hypothesis has been debated given the paucity of evidence, for example, the differences in crustal thickness, the compositional gap between MP and OJP basalts and the apparent older age of both plateaus relative to HP remain unresolved. Here we investigate the geochemical and 40Ar-39Ar ages of dredged rocks recovered from the OJP's eastern margin. Volcanic rocks having compositions that match the low-Ti MP basalts are reported for the first time on the OJP and new ~ 96-116 Ma and 67-68 Ma 40Ar-39Ar age data bridge the temporal gap between OJP and HP. These results provide new evidence for the Ontong Java Nui hypothesis and a framework for an integrated tectonomagmatic evolution of the OJP, MP, and HP. The isotopic data imply four mantle components in the source of OJN that are also expressed in present-day Pacific hotspots sources, indicating origin from (and longevity of) the Pacific Large Low Shear-wave Velocity Province.

Design and fabrication of a perpendicular magnetic tunnel junction based nonvolatile programmable switch achieving 40% less area using shared-control transistor structure.

A compact nonvolatile programmable switch (NVPS) using 90 nm CMOS technology together with perpendicular magnetic tunnel junction (p-MTJ) devices is fabricated for zero-standby-power field-programmable gate array. Because routing information does not change once it is programmed into an NVPS, high-speed read and write accesses are not required and a write-control transistor can be shared among all the NVPSs, which greatly simplifies structure of the NVPS. In fact, the effective area of the proposed NVPS is reduced by 40% compared to that of a conventional MTJ-based NVPS. The instant on/off behavior without external nonvolatile memory access is also demonstrated using the fabricated test chip.

Mode of inheritance of HLA-DRB1 shared epitope in Japanese familial rheumatoid arthritis.

OBJECTIVE: To clarify the mode of genetic contribution of the HLA-DR shared epitope (SE) to the pathogenesis of familial cases of Japanese rheumatoid arthritis (RA). METHODS: Fifty-three unrelated Japanese RA families that had more than 2 affected sibs were selected. The HLA-DR shared epitope typing was carried out by the PCR method and PCR-SSCP (single stranded DNA conformation polymorphism) method. Affected sib pair analysis was carried out using the MAPMAKER/SIB 2.0 program. The mode of inheritance was also calculated based on the sharing of genes identical by descent (IBD) between siblings in each of the 53 affected sib-pairs (propositus and the 2nd affected sib). RESULTS: The maximum LOD score of HLA-DR was 0.437, and the sharing of 2 IBDs, 1 IBD, and no IBDs between affected sibs were 0.330, 0.500, and 0.170, respectively. The sharing distribution of IBD was confirmed to be compatible with the dominant or additive mode since the observed gene frequency of SE was 0.255. CONCLUSION: The HLA-DR shared epitope participated in the pathogenesis of familial cases of Japanese RA. The SE contributes to this pathogenesis in either the dominant or additive mode of inheritance.

The effect of activity and type of rheumatoid arthritis on the flexible implant arthroplasty of the metacarpophalangeal joint.

A retrospective study was performed on 184 Swanson flexible implant arthroplasties of the metacarpophalangeal joint in 75 hands of 64 patients with rheumatoid arthritis, to investigate the influence of systemic factors on the clinical and radiological results. The mean follow-up period was 6 years. The postoperative serum C-reactive protein level was found to affect postoperative pain, and there was a larger extension lag and more subsidence of the implant in those with the mutilating type of the disease.

Intra-articular injection of hyaluronate (SI-6601D) improves joint pain and synovial fluid prostaglandin E2 levels in rheumatoid arthritis: a multicenter clinical trial.

OBJECTIVE: The relationship between clinicalfeatures and biochemical parameters of synovialfluid after serial intra-articular injections of sodium hyaluronate (SI-6601D) was investigated. METHODS: SI-6601D (sodium hyaluronate with an average molecular weight of 8.4 x 10(5); 25mg/2.5ml/syringe) was injected intra-articularly into the knees of 25 patients with rheumatoid arthritis (RA) every week for 5 consecutive weeks. Clinical and biochemical parameters were monitored before and after injection. Clinicalfindings included pain, as a summation of 3 categories (pain at rest, pain in motion and pain in passive motion, each assessed on a 4-step rating scale), and inflammation, also as a summation of 3 categories (swelling, patellar ballotement and local warmth, each assessed on a 4-step rating scale). Pain on walking of patient was qualitatively assessed by visual analogue scale (VAS). The aspirated volume of synovialfluid (SFV) was recorded and levels of prostaglandin (PG) E2, transforming growth factor beta-1, tumor necrosis factor alpha, interleukin I receptor antagonist, chondroitin 4-sulfate (C4S) and chondroitin 6-sulfate were measured. RESULTS: Significant improvement in pain symptoms (p < 0.0001), inflammation (p < 0.0001), VAS pain (p < 0.001) and SFV (p < 0.05) were observed after the 5 injections. Levels of PGE2 (p < 0.05) and C4S (p < 0.05) in the synovialfluid were significantly decreased. DISCUSSION: SI-6601D improved local clinical symptoms in RA patients by suppressing PGE2 and, therefore, may be a useful treatment for local inflammation in RA.

Flexible hinge toe implant arthroplasty for rheumatoid arthritis of the first metatarsophalangeal joint: long-term results.

We report the long-term clinical results and survival rate of the implant in flexible hinge toe implant arthroplasty of the first metatarsophalangeal joint, combined with a shortening oblique osteotomy of the metatarsal neck in the lateral toes, in patients with rheumatoid arthritis. Between 1983 and 1990, arthroplasty was performed on 97 feet in 66 patients. Twenty-seven patients died; follow-up information was available for 60 feet in the remaining 39 patients, who were followed for an average of 12 years. Twenty-nine patients (74%) were satisfied with the outcome after surgery, 7 were satisfied but had some pain or recurrent deformities, and 3 were unsatisfied. Radiologically, visible fracture was identified in nine implants. Four implants were removed because of infection (n = 2) or recurrent deformity (n = 2); no implant was removed because silicone synovitis developed. With revision as the endpoint, the implant survival rate was 93% at 10 years, and with radiographic implant fracture as the endpoint, the implant survival rate was 87% at 10 years. Shortening oblique osteotomy of the lateral toes appeared to decrease the rate of implant fracture and should be performed concomitantly with implantation when rheumatoid forefoot deformities are being reconstructed.

Mineral density and histomorphometric assessment of bone changes in the proximal tibia early after induction of type II collagen-induced arthritis in growing and mature rats.

Bone changes in both actively growing (6-week-old) and mature (6-month-old) rats with collagen-induced arthritis (CIA) were investigated in order to clarify the mechanisms of osteoporosis near inflamed joints in patients with early rheumatoid arthritis (RA) and juvenile RA. In female Sprague-Dawley rats, the proximal tibiae from the CIA and control groups early after immunization, when any influence of immobilization due to joint pain and swelling is minimal, were studied using dual X-ray absorptiometry and histomorphometry after double-labeling with tetracycline. Arthritis developed within 10-14 days after immunization in both growing and mature rats. Physical activity, growth, and body weight continued to resemble that of the control group for at least 10 days. The bone mineral density in the proximal tibia did not differ significantly between the CIA and control groups. In growing rats, a highly significant increase in bone resorption, and decreases in bone formation and trabecular bone volume became evident histomorphometrically before visible signs of arthritis had developed. In mature rats, bone formation was markedly decreased without an increase in bone resorption. The differences in the reaction between growing and mature rats reflected a difference in the number of remodeling sites (units) and an uncoupling between osteoblasts and osteoclasts. We conclude that osteoporosis near inflamed joints results from an imbalance between bone resorption and formation caused by immune reactions in the CIA rats. Moreover, a decrease in bone formation may, in part, precede the clinical onset of arthritis.

Distribution and expression of transforming growth factor-beta and platelet-derived growth factor in the normal and glaucomatous monkey optic nerve heads.

PURPOSE: Remodeling of the extracellular matrix occurs in the lamina cribrosa in progressed glaucomatous optic nerve damage including disc cupping. We examined immunohistochemical changes in the transforming growth factor (TGF)-beta and platelet-derived growth factor (PDGF) in the optic nerve head in an experimentally induced glaucoma model. METHODS: We used 3 cynomolgus and 2 Japanese monkey eyes. Glaucoma was induced by repeated argon laser photocoagulation of the chamber angle. Eyes were enucleated after disc cupping had formed 3 to 5 months after photocoagulation. The optic nerve head was examined for expression of TGF-beta1, -beta2 and -beta3 and PDGF-A and -B in frozen sections and by the biotin ExtraAvidin-alkali phosphatase method. RESULTS: Normal monkey eyes showed TGF-beta1, -beta2 and -beta3, and PDGF-A and -B in the optic nerve head including the nerve fibers, glial cells, and vascular cells. Glaucomatous eyes showed stronger expression of TGF-beta1 and -beta2 in the glial cells around the lamina cribrosa. The staining intensities for TGF-beta3, PDGF-A and -B were the same as in normal eyes. CONCLUSIONS: Eyes with experimental glaucoma showed higher expression of TGF-beta1 and -beta2 around the lamina cribrosa. These findings may show upregulation of extracellular matrix production as related to remodeling of the lamina cribrosa in glaucoma.

Total knee arthroplasty in a patient with rheumatoid arthritis and spontaneous fusion of the right hip.

Abstract Bilateral total knee arthroplasty for a painful stiff knee was performed in a 50-year-old woman with rheumatoid arthritis who had spontaneous fusion of the right hip. Despite several manipulations, the range of motion of the right knee worsened. After total hip arthroplasty and ipsilateral knee revision, the right knee had a stable range motion of -15° to 75°. This case suggests that even if the ankylosed hip is in a good position, ipsilateral knee arthroplasty with a fused hip may result in a poorer range of motion than that after total hip arthroplasty.

Urinary thrombomodulin in patients with rheumatoid arthritis: relationship to disease subset.

In 110 patients with rheumatoid arthritis (RA), the mean (+/- SD) urinary thrombomodulin (TM) concentration was 74.4+/-19.5 ng/mg creatinine (Cre), which was significantly higher than the mean in age-matched healthy controls (49.9+/-10.8 ng/mg Cre; p<0.0001). The mean urinary TM concentration in the RA subset with least erosive disease (LES) was 65.2+/-12.4 ng/mg Cre (n = 41), with more erosive disease (MES) was 77.4+/-20.4 ng/mg Cre (n = 58) and with mutilating disease (MUD) was 92.6+/-20.2 ng/mg Cre (n = 11). TM in the MUD group was the highest of the three subsets (ANOVA, p<0.0001). By contrast, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the MES and MUD groups were not significantly different. Urinary TM levels may allow differentiation of RA subsets, unlike markers of inflammation such as ESR and CRP.

Structural mechanisms of bone loss in iliac biopsies: comparison between rheumatoid arthritis and postmenopausal osteoporosis.

To assess the mechanisms that cause generalized osteoporosis in rheumatoid arthritis (RA), 40 postmenopausal women with RA (46-74 years) and 40 age-matched controls with osteopenia underwent iliac bone biopsies. A structural analysis of histomorphometry and two-dimensional strut analysis were performed. As compared to those with primary osteoporosis, there were a few unique characteristics in those with RA. Trabecular thickness and wall thickness declined with age, and this decline was especially accelerated by glucocorticoids. Decreased connectivity of the trabecular (Nd.Nd) was more prominent than the disappearance of the nodes. The connectivity of cortical bone to the nodes (Ct.Nd) and cortical thickness significantly decreased with age. With glucocorticoid therapy, the disappearance of the nodes was accelerated. In the case of vertebral compression fractures, the parameters of Nd.Nd and Ct.Nd significantly decreased. Although a bone biopsy is needed to analyze strut, this method is useful to evaluate the quality or intensity of the bone.

Histomorphometric assessment of bone changes in rats with type II collagen-induced arthritis.

Numerous studies have demonstrated bone loss in rats following immobilization by tenotomy or nerve sectioning and following ovariectomy. However, few experiments have focused on bone change in rats with arthritis. We investigated bone loss in the proximal tibia and lumbar vertebra in rats with type II collagen-induced arthritis, an experimental model of rheumatoid arthritis, using histomorphometry. Bone loss in the early phase after immunization reflected a significant increase in numbers of osteoclasts and temporarily decreased bone formation. In the proximal tibia, near an arthritic joint, osteoclast numbers associated with bone trabeculae were increased four times over control numbers 4 weeks after immunization. In the lumbar vertebra, where arthritis was not shown, recruitment of osteoclasts occurred later than in the proximal tibia. With time, in both the proximal tibia and lumbar vertebra bone resorption normalized, but bone formation rate and double-label surface by tetracycline, a parameter reflecting bone formation, were increased above control values. We conclude that differences between the proximal tibia and lumbar vertebra probably reflected resumption of function as well as distance from areas of inflammation. These findings indicate that collagen-induced arthritis in rats is a useful model not only of autoimmunity, but also of juxta-articular and generalized osteoporosis in rheumatoid arthritis.

[The effects of single mitomycin C application on the expression of matrix metalloproteinase in the sclera and aqueous of albino rabbits].

BACKGROUND: Topically applied mitomycin C, which is used to prevent scar formation after filtering surgery for glaucoma, is known to cause reduction in scleral cells and abnormal remodelling of scleral extracellular matrices. I examined in this study the effects of mitomycin C on the expression of matrix metalloproteinase in the sclera and aqueous humor. METHOD: Mytomycin C was applied for 5 minutes to the bared sclera of 14 albino rabbit eyes. The sclera was organ cultured after 1 week, 2 weeks, and 1 month. The culture medium was subjected to zymography to quantitate the gelatinase activity. In situ zymography was performed on the sclera obtained 1 month after mitomycin C application. The aqueous was also subjected to zymography. FINDINGS: The scleral tissue and its cultured media showed enhanced gelatinase activity. The aqueous showed no changes in gelatinase activity. CONCLUSION: Increased activity in matrix metalloproteinase may be involved in the abnormal remodelling of scleral extracellular matrices after application of mitomycin C.

[Changes in transforming growth factor-beta and platelet-derived growth factor in the optic nerve head in monkey experimental glaucoma].

PURPOSE: Remodeling of the extracellular matrix occurs in the lamina cribrosa in progressed glaucomatous optic nerve damage including disc cupping. We examined immunohistochemical changes in the transforming growth factor (TGF)-beta and platelet derived growth factor (PDGF) in the optic nerve heads in experimentally induced glaucoma. METHODS: We used 3 cynomolgus and 2 Japanese monkey eyes. Glaucoma was induced by repeated argon laser photocoagulation of the chamber angle. Eyes were enucleated after disc cupping had formed 3 to 5 months after treatment. The optic nerve head was examined for expression of TGF beta 1, beta 2, and beta 3, and PDGF A and B in frozen sections and by the biotin-ExtrAvidin-Alkali Phosphatase method. FINDINGS: Normal monkey eyes showed TGF beta 1, beta 2, and beta 3, and PDGF A, and B in the optic nerve head including the nerve fibers, glial cells, and vascular cells. Glaucomatous eyes showed stronger expression of TGF beta 1 and beta 2 in the glial cells around the lamina cribrosa. The staining intensities for TGF beta 3, PDGF A, and PDGF B were the same as in normal eyes. CONCLUSION: Eyes with experimental glaucoma showed higher expressions of TGF beta 1 and beta 2 around the lamina cribrosa. This finding may show upregulation of extracellular matrix production as related to remodeling of the lamina cribrosa in glaucoma.

Progression of rheumatoid arthritis of the cervical spine: radiographic and clinical evaluation.

Cross-sectional and longitudinal studies were conducted to observe progression of rheumatoid arthritis in the cervical spine. Two hundred and ninety-seven patients were enrolled in the cross-sectional study. Both upper and lower cervical spine involvement increased with disease duration. The relationship between atlanto-axial motion and the development of subaxial subluxation was inconclusive. Eighty-seven patients were enrolled in the longitudinal study and were followed for at least 5 years. In about half of these patients, rheumatoid changes started from the upper cervical spine, with rheumatoid changes beginning from the lower cervical spine in about 8% of patients. Neurological deficits were correlated with radiographic changes but neck pain did not correlate with radiographic changes. As to the upper cervical spine, the parameter most influencing neurological deficits was found to be the minimum value of the atlanto-axial angle in flexion, by multivariate analysis using a multiple logistic model. Neurological deficits were seen in more than half the patients when the atlanto-axial angle in flexion was 5 degrees or less.

Experimental glaucoma model in the rat induced by laser trabecular photocoagulation after an intracameral injection of India ink.

A simple and reproducible rodent glaucoma model is required to elucidate the pathophysiology of damage to the optic nerve. We developed chronically elevated intraocular pressure (IOP) unilaterally in rats by injecting india ink into the anterior chamber of one eye using a 30-gauge needle. One week later, trapped carbon particles in the chamber angle formed a black band along the corneal limbus in the injected eyes. We performed direct laser photocoagulation without a gonio lens, and selectively burned the trabecular meshwork. Intraocular pressure was measured every week and laser photocoagulation was repeated until mean IOP in the experimental eyes rose above 25 mmHg. Unilateral IOP elevation was attained in all rats within 4 weeks. Twelve weeks after ink injection, we sacrificed the rats and excised the eyes for histologic analysis. The anterior chamber angle showed peripheral anterior synechia caused by laser photocoagulation, and carbon particles were engulfed by macrophages that infiltrated the ciliary cleft. In the optic nerve head, a remarkable decrease in the nerve fiber layer and cavernous degeneration were observed, suggesting glaucomatous optic nerve damage. This experimental rodent model should facilitate the study of the complex mechanisms involved in glaucoma.

[Experimental glaucoma model in the rat with laser trabecular photocoagulation after intracameral injection of India ink].

We tried to create an experimental glaucoma which is simple and highly reproducible in rodents. India ink was injected into the anterior chamber with a 30-gauge needle. The carbon particles were trapped in the chamber angle and formed a black band along the corneal limbus one week later. This area was then photocoagulated anteroposteriorly with an argon laser. Photocoagulation was repeated until the intraocular pressure was elevated to 25 mmHg or more by pneumotonometry performed at a one-week interval. The above procedure was applied to one eye of 7 rats with the fellow eye serving as control. Chronic elevation of intraocular pressure was obtained in all the 7 treated eyes. The eyes were then enucleated and examined by light microscopy. Carbon particles were phagocytosed by macrophages in the intertrabecular spaces. Peripheral anterior synechias were also present. The optic nerve-head showed remarkable decrease in nerve fibers and cavernous degeneration suggestive of glaucomatous optic nerve damage. This experimental model promises to be of value in further studies of glaucomatous optic nerve damage.