Background: The discovery and development of novel biomarkers that could facilitate early diagnosis and thus prevent the progression of atherosclerosis-related diabetes mellitus (DM), cerebral infarction (CI), and cardiovascular disease (CVD) has garnered much research interest. Notably, recent reports have described a number of highly sensitive antibody markers. In this study, we aimed to identify additional antibody markers that would facilitate screening. Methods:The amplified luminescent proximity homogeneous assay (AlphaLISA) method, which incorporates glutathione-or streptavidin-donor beads and anti-human-IgG-acceptor beads, was used to evaluate serum antibody levels in serum samples. The protein array method was used for the initial screening, and peptide arrays were used to identify epitope sites. Results:The protein array identified SH3 domain-binding protein 5 (SH3BP5) as a target antigen of serum IgG antibodies in the sera of patients with atherosclerosis. We prepared recombinant glutathione S-transferase (GST)-fused SH3BP5 protein. Peptide arrays revealed that the epitope site recognized by serum antibodies is located within amino acids 161-174 of SH3BP5. AlphaLISA revealed significantly higher serum antibody levels against both the SH3BP5 protein and peptide in patients with DM, acute-phase CI, transient ischemic attack, CVD or chronic kidney disease (CKD), than in healthy donors. Furthermore, areas under the receiver operating characteristic curves of these antibodies were higher in patients with CKD and DM than in other patients. Spearman correlation analysis revealed associations between the serum antibody levels against SH3BP5 peptide and artery stenosis, hypertension, and smoking. Conclusions:The serum anti-SH3BP5 antibody marker appears to be useful for estimating the progress of atherosclerosis and may discriminate atherosclerosis associated with hypertension and/or habitual smoking.

Transient ischemic attack (TIA) is a predictor for cerebral infarction (CI), and early diagnosis of TIA is extremely important for the prevention of CI. We set out to identify novel antibody biomarkers for TIA and CI, and detected matrix metalloproteinase 1 (MMP1), chromobox homolog 1 (CBX1), and chromobox homolog 5 (CBX5) as candidate antigens using serological identification of antigens by recombinant cDNA expression cloning (SEREX) and Western blotting to confirm the presence of serum antibodies against the antigens. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) revealed that serum antibody levels were significantly higher in patients with TIA or acute-phase CI (aCI) compared with healthy donors (P < 0.01). Spearman’s correlation analysis and multivariate logistic regression analysis demonstrated that levels of anti-MMP1, anti-CBX1, and anti-CBX5 antibodies were associated with age, cigarette-smoking habits, and blood pressure. Thus, serum levels of antibodies against MMP1, CBX1, and CBX5 could potentially serve as useful tools for diagnosing TIA and predicting the onset of aCI.

Twenty-eight symptomatic dural fistulas involving the transverse and sigmoid sinuses were treated between 1978 and 1986 with a variety of treatment modalities. Occipital artery compression therapy resulted in a complete cure in two of nine patients (22%) and improvement in three of nine (33%). There were no complications from this treatment. Patients who were excluded or in whom compression therapy failed were treated with embolization alone or in conjunction with surgery. Of the 17 patients who underwent embolization alone, ten were cured and six were improved. Six patients had a combination of embolization and surgery; four patients were cured and two improved. There were three complications in this series, one related to surgery and two related to embolization.

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The development of abnormal communications between dural arteries and dural veins (crack-like vessels) is regarded as the essential part of the pathogenesis of DAVFs, and sinus thrombus is not thought to be an essential lesion of DAVFs. It might be postulated that sinus hypertension caused by stenocclusive disease of the venous sinuses triggers the development of fistulous connections between arteries and veins in the dural wall, which may result in increasingly dilated venules and the formation of DAVFs.

Cerebral infarction (CI), cardiovascular disease (CVD), diabetes mellitus (DM) and chronic kidney disease (CKD) are atherosclerosis-related diseases, which are major causes of health damage. For early and sensitive diagnosis, development of novel biomarkers is expected and of significant practical importance. First screening was carried out by phage expression cloning to identify antigen proteins recognized by serum IgG antibodies in patients with atherosclerosis. RPA2, LRPAP1, EEF1A1, SPOCK1, LOC729260, tubulin beta 2C (TUBB2C) and KIAA0020 markers were identified. We then compared the serum antibody levels against the candidate proteins between healthy donors (HD) and patients with CI, CVD, DM, or CKD by Alpha (amplified luminescent proximity homogeneous assay)-LISA method. The results showed that the serum TUBB2C antibody levels were significantly higher in patients with CI, DM, or CKD than those in HD. Using the average + 2SD of HD as the cut-off value, the positive thresholds of TUBB2C antibody markers were 14.8% in CI, 25.8% in DM, and 18.3% in CKD. TUBB2C antibody levels were well correlated with artery stenosis degrees such as plaque score, maximum intima-media thickness and cardio ankle vascular index. Consequently, TUBB2C antibody markers are useful to diagnose atherosclerosis, DM, and CKD, and can be applied to the prediction of the onset of CI. The serum anti-TUBB2C antibody markers are useful for the diagnosis of DM and CKD.

Chondrogenesis is an essential component of endochondral fracture healing, though the molecular and cellular events by which it is regulated have not been fully elucidated. In this study, we used a rat model of closed fracture healing to determine the spatial and temporal expression of genes for cartilage-specific collagens. Furthermore, to determine the effects of basic fibroblast growth factor (bFGF) on chondrogenesis in fracture healing, we injected 100 microg recombinant human bFGF into the fracture site immediately after fracture. In normal calluses, pro-alpha1(II) collagen mRNA (COL2A1) was detected in proliferative chondrocytes beginning on day 4 after the fracture, and pro-alpha1(X) collagen mRNA (COL10A1) in hypertrophic chondrocytes beginning on day 7. In FGF-injected calluses, the cartilage enlarged in size significantly. On day 14, both COL2A1- and COL10A1-expressing cells were more widely distributed, and the amounts of COL2A1 and COL10A1 mRNAs were both approximately 2-fold increased when compared with uninjected fractures. Temporal patterns of expression for these genes were, however, identical to those found in normal calluses. The number of proliferating cell nuclear antigen-positive cells was increased in the non-cartilaginous area in the bFGF-injected calluses by day 4. The present molecular analyses demonstrate that a single injection of bFGF enhances the proliferation of chondroprogenitor cells in fracture callus, and thus contributes to the formation of a larger cartilage. However, maturation of chondrocytes and replacement of the cartilage by osseous tissue are not enhanced by exogenous bFGF, and this results in the prolonged cartilaginous callus phase. We conclude that, in the healing of closed fractures of long bones, exogenous bFGF has a capacity to enlarge the cartilaginous calluses, but not to induce more rapid healing.

CT findings in 6 autopsy cases of subcortical arteriosclerotic encephalopathy (SAE) are reported. A diffuse area of nonhomogeneous decreased density was observed in the deep white matter of both cerebral hemispheres, together with moderate dilatation of the lateral ventricles and ragged margins. The most characteristic pathological findings at autopsy were a diffuse area of incomplete infarction containing multiple small infarcts as well as cyst formation and marked stenotic atherosclerotic changes in the medullary arteries. Clinical features included patchy mental lapses, frontal-lobe syndromes, minor motor signs, and hypertension. The authors feel that SAE or a similar disease might occur in most cases of multi-infarct dementia.