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.

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.

Comparative study of carbohydrate-protein complexes. III. Peptide structures of the linkage region in proteoglycans of human, porcine and shark cartilages.

Chondroitin sulfite peptidoglycans were prepared by the pronase digestion of cartilages from human knee joints, porcine tracheae, and shark crania. The beta-elimination and sulfite addition reaction of these peptidoglycans yielded cysteic acid-containing peptides, and the amino acid sequences of some of them were determined. The finding that human and porcine peptidoglycans have the same sequence in the linkage region as that of the bovine peptidoglycan reported previously suggested that there is a common structural feature in the core proteins of these mammalian cartilage proteoglycans. The results also support the view that -Ser-Gly- is the minimum requisite for the formation of the xylosylserine linkage of proteochondroitin sulfates.

Prolidase deficiency with imidodipeptiduria. A familial case with and without clinical symptoms.

A 23-year-old female with chronic leg ulcer was found to excrete the massive imidopeptides, among which Asp-Pro, Glu-Pro and Gly-Pro were identified. Essentially no prolidase activity was measured in her erythrocytes, while prolinase activity was within a normal range. Her 26-year-old brother also showed imidopeptiduria and erythrocyte prolidase deficiency, but no clinical symptoms were observed. Erythrocytes from her father and 30-year-old brother, who excreted no significant amounts of imidodipeptides, showed intermediate values for the prolidase activity between those for the patient and for normal adults, suggesting that they are heterozygous for this autosomal recessive disorder.

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.

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.

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.

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.

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.

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.

[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.

[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.

A twenty-year period in mass screening for uterine cervical cancer in Fukushima Prefecture.

To explore the change in age distribution of patients with uterine cervical cancer and its precursors, we analyzed 2,168,923 women in a series of mass screening for uterine cervical cancer in Fukushima Prefecture. The first examination rate was not increased over a 20-year period. During the screening period, severe dysplasia was found in 693 women, carcinoma in situ in 672 women, microinvasive carcinoma in 517 women, and frank invasive carcinoma in 421 women. The numbers of patients with frank invasive carcinoma was decreased gradually in every age group, which might reflect the effectiveness of our mass screening project. Although the detection rates of severe dysplasia, carcinoma in situ and microinvasive carcinoma have not changed in patients groups over 40 years old, the detection rates were increased in patients under the age of 39. These results may reflect a recent tendency for cervical cancer to increase in young women. It is important, therefore, to increase the screening rate for young women to prevent the progression with advanced cervical cancer.

[Spontaneous speech disturbances in so called transcortical motor aphasia--comparison of 3 cases with the different lesion sites].

So called transcortical motor aphasia (TCMA) is frequently subdivided, because the clinical features and the localization of the lesions are variable. The authors have been attempting to classify TCMA into three types according to the distribution of the lesions, such as Type F 1, Type F 2 and Type F 3. Case 1 N.S. belongs to Type F 1 showing the clinical features of TCMA with bleeding in the territory of the left anterior cerebral artery. Case 2 M.E. belongs to Type F 2 (published case). This case is similar to Luria's dynamic aphasia in its clinical features and results from the lesions including the posterior parts of left middle frontal gyrus. Case 3 N.T. belongs to Type F 3 who recovered from typical Broca aphasia after language training for four years. The case is similar to Goldstein's Type 1 of TCMA in its clinical features. These three cases are compared with regard to the fundamental bases of spontaneous speech disturbance. The items of comparison are as follows; the volume of speech production and the the time taken to start speech, word fluency test, cue effects necessary for the success of sentence constructions grammatical ability. The results are summerized in Table 2. Type F1 shows the most conspicuous defect of spontaneous speech, but no disturbance in grammatical ability. And when the top word of a sentence (a subject word) is given by the examiner, the patient can construct a structurally correct sentence. These findings imply that the spontaneous speech disturbance of Type F 1 is due to a defect of the starting mechanism of speech.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitochondrial glutamic oxaloacetic transaminase and its clinical significance.

The m-GOT were studied in 57 patients with liver diseases, diagnosed by peritoneoscopy and biopsy. In acute hepatitis, the m-GOT rose to 100 units or there-about. But in chronic hepatitis, even in hepatitis B with sublobular necrosis, the m-GOT were low and 20--30 units. On the other hand, in alcoholic hepatitis, the m-GOT were 50--60 units which may be considered to be higher than expected for comparable their histological necrotic findings. These values were higher than OCT, which were measured at the same time. This results showed that there might be m-GOT induction by alcohol. In liver cirrhosis lower values were obtained. Generally m-GOT was liable to be lower as the lobular distortion was getting severer.

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.