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Background Among human oral bacteria, particular kinds of Streptococcus mutans (SM) known as dental caries pathogens contain a collagen-binding protein, Cnm, and show platelet aggregation inhibition and matrix metalloproteinase-9 activation. We have previously reported that these strains may be a risk factor for intracerebral hemorrhage. As a major sample-providing hospital, we report the clinical details, including intracranial aneurysms and ischemic stroke. Methods After the study received approval from the Ethical Committee, 429 samples of whole saliva were obtained from patients who were admitted to or visited our hospital between February 16, 2010, and February 28, 2011. The study cohort comprised 48 patients with cardioembolic stroke (CES), 151 with non-CES infarct, 54 with intracerebral hemorrhage (ICH), 43 with ruptured intracranial aneurysm (RIA), and 97 with unruptured intracranial aneurysm (UIA). Cultured SM was identified as Cnm-positive when the corresponding gene was positive. The results were compared with those from 79 healthy volunteers. Relationships between Cnm-positive SM and known risk factors, including hypertension, diabetes, hyperlipidemia, smoking, and alcohol consumption, were analyzed. Results A statistically significant high Cnm-positive rate was observed in patients with CES, non-CES infarct, ICH, and RIA (P = 0.002, 0.039, 0.013, and 0.009, respectively). There were no relationships between Cnm-positive SM and known risk factors. Conclusions Specific types of oral SM can be a risk factor for cardioembolic infarct, intracerebral hemorrhage, and intracranial aneurysm rupture. Further study is needed.

Background Sleep has been reported to be an important factor in bone metabolism, and sympathetic nervous system activity has been reported to regulate bone metabolism. In this study, we evaluated the association between sleep, sympathetic nervous system activity, and bone mass. Methods The study subjects were 221 individuals (108 males; 113 females; mean age: 55.1 ± 7.0 years) divided into two groups: those who slept for less than 6 h a day (short sleep [SS] group), and those who slept 6 h or longer (normal sleep [NS] group). The groups were compared with regard to lifestyle, cortical bone thickness, cancellous bone density, bone metabolism markers, blood leptin levels, and sympathetic nervous system activity as evaluated by heart rate variability analysis. Results Significant differences were observed between the two groups in cortical bone thickness, blood TRACP-5b, and leptin levels. The L/H ratio (an index of sympathetic nervous system activity) was higher in the SS group than in the NS group. Significant negative correlations were observed between cortical bone thickness and both the L/H ratio and leptin levels, and a significant positive correlation was observed between the L/H ratio and leptin levels. Conclusions Short sleep was associated with a decline in cortical bone thickness due to the promotion of bone resorption and sympathetic nervous system hyperactivity in the middle-aged group. Leptin levels and cortical bone thickness were found to be closely related, suggesting that cortical bone mass may be regulated via interaction with the leptin-sympathetic nervous system.

Background Vascular dementia is related to intracranial arteriosclerosis associated with deep white matter lesions (DWMLs). DWMLs have been linked to thrombogenesis due to sustained platelet activation; therefore, an accurate hematological marker is needed. This study was done to evaluate the usefulness of a new method to examine the function of activated platelets in order to assess DWMLs associated with cognitive decline. Methods A total of 143 individuals (70.4 ± 6.1 years old) who underwent hospital-based health screening using head MRI were evaluated. DWLs were evaluated on T2-weighted and FLAIR images by semi-quantitatively grading them from Grade 0 (none) to Grade 3 (severe) using the Fazekas classification. Cognitive function was evaluated using the MMSE and the word fluency test. Platelet activation was assessed using fluorescence-labeled anti-human platelet monoclonal antibodies and semi-quantitatively determining PAC-1- and CD62P-positive rates by flow cytometry. Results Significant increases in hypertension and CD62P levels were observed with increasing DWML grade (2.6% in Group 0, 3.1% in Group 1, 4.1% in Group 2, and 5.0% in Group 3). CD62P levels were defined as elevated when they were above the mean + 2SD of the Grade 0 group, and the odds ratio of the Grade 2 + 3 group was 3.03. A significant negative correlation was observed between CD62P levels and word fluency tests or the MMSE score. Conclusion Elevations in CD62P levels, which reflect platelet function activation, were associated with white matter lesions accompanied by a decline in cognitive function. CD62P levels may be useful as a sensitive clinical marker for the early detection of DWMLs with cognitive decline.

A B S T R A C T Stroke incidence and cognitive decline are related to progression of arteriosclerosis in intracranial DWLs. However, the relationships between DWLs and factors associated with their progression, including CKD, have not been fully elucidated using longitudinal MRI. Of 291 individuals (184 males, 107 females; age 66.9 6.1 years) who had voluntarily participated in a hospital-based health check-up and underwent repeated brain MRI scans in 2003 and 2008, 273 were evaluated in this study. The DWL group included those having DWL without progression, and the DWL progression (DWLP) group included those having an increase in grade number according to the Fazekas classification. Unimpaired age-matched subjects with no brain MRI abnormalities constituted Group C. The Mini-Mental State Examination (MMSE) and verbal fluency tasks were used for objective cognitive evaluations according to the MR evaluation schedule in 2008. Associations between DWLs and vascular risk factors were examined. DWLP occurred in 9.2% of subjects. Compared to Group C subjects, DWL and DWLP group subjects had high odds ratios (ORs) for hypertension (HT) (2.23 and 2.92, respectively) and CKD (1.40 and 2.41, respectively). After adjustment for potential confounders, the ORs of CKD for DWLs remained significant (1.13 and 1.43, p < 0.05). DWLs and DWLP were associated with low cognitive scale scores and increased CKD. In conclusion, CKD was associated with DWLs and DWLP as an independent risk factor and a lower level of cognitive function 5 years after CKD was identified. Successful CKD therapy may be expected to prevent DWLP.

In our previous proteomic study in rat liver damaged by carbon tetrachloride, soluble catechol-O-methyltransferase (COMT) increased as a phosphorylated form and decreased as a dephosphorylated form. This finding raised the possibility that the COMT protein is associated with liver function. Thus, we hypothesized that (1) the COMT gene contributes to liver homeostasis and (2) a COMT polymorphism (rs4680: Val158Met) causing thermolability of enzymatic activity affects liver enzymes (e.g., aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (γ-GT)) in serum. To investigate (2), we statistically analyzed the association between COMT genotypes and serum ALT activity in a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We conducted a multiple logistic regression analysis for males (n=838) and females (n=970). Those participants having missing values or a past history of liver cirrhosis or liver cancer were excluded. ALT values were divided into two; elevated (30IU/L ≤; males n=239, females n=90) and normal (30IU/L; males n=599, females n=880). In females, non-adjusted and adjusted odds ratios for ALT values in the rs4680 A/A homozygote (n=126) compared with the wild-type G/G homozygote (n=397) were 0.37 (95% CI 0.14-0.96) and 0.34 (95% CI 0.13-0.93), respectively. In males, an analysis of the population aged 35-69 did not reveal any significant difference, but the population aged 45-54 had a significant difference in the non-adjusted and adjusted odds ratio in the G/A heterozygote (n=89) (0.50 (95% CI 0.27-0.92) and 0.35 (95% CI 0.18-0.71)) and in the A/A homozygote (n=22) (0.34 (95% CI 0.11-0.99) and 0.22 (95% CI 0.07-0.72)), compared with the G/G homozygote (n=88). These data suggest that the COMT polymorphism affects serum ALT activity to maintain liver function.

HTLV-1 associated myelopathy (HAM) has been known to reveal various clinical manifestations of autonomic dysfunction; thus the focus of the present study was to investigate whether or not thoracic spinal cord injury frequently observed in HAM patients leads to cardiovascular autonomic dysfunction. The subjects consist of 18 patients in the chronic phase of HAM (group HAM) and 29 normal subjects (group C). They were examined for CVR–R and total heart rate. A power spectral analysis of R–R interval variability of their 24-hour Holter ECGs was also done. High frequency (HF) was an indicator of parasympathetic activity, while the low to high frequency ratio (L/H) was used as an indicator of sympathetic activity. Nominated HAM patients were evaluated by neurological examination using clinical indicators of HAM (EDSS, OMDS and FIM). To examine the degree of atrophy of the upper thoracic spinal cord, we performed individual MR (magnetic resonance) imaging of HAM spinal cords. Correlations between the above indicators and clinical indicators of HAM were examined. The L/H ratio was significantly lower in group HAM (1.67 ± 0.79) than in group C. Significant reduction in the L/H ratio was observed in 8 (88.9%) of 9 patients in group HAM with orthostatic hypotension. The L/H ratio was significantly low in HAM patients with thoracic cord atrophy, strongly suggesting that the coexistence of a thoracic cord lesion is associated with a reduction of cardiovascular sympathetic activity. In conclusion, cardiovascular autonomic dysfunction in HAM patients is mainly associated with cardiac sympathetic efferent abnormalities in the upper thoracic segments.

The use of stereotaxic neurosurgery in rodent models of human disease requires the alignment of central nervous system (CNS) structures that can be identified and surgically approached with great accuracy. Current technologies make possible development of mouse lines with enhanced predispositions for the development of various diseases including tumors. When such tumors arise in the brain their location is unpredictable. Obtaining a biopsy or stereotaxically delivering local therapy requires that the site of such tumors be known with great precision. We devised a method to correlate images of mouse brain tumors acquired by magnetic resonance imaging (MRI) with stereotaxic coordinates that can be used for obtaining biopsies or administering local therapy. We constructed a head holder containing a pair of tubes filled with a substance that could be imaged by MR and which were separated by varying distances. This allowed the precise localization of the tumor in all three dimensions. The strategy we employed is adaptable to other imaging modalities and to other body sites.

light reflex was measured by means of video-pupillography. Evaluated items included initial pupil diameter (D1), contraction ratio of pupils (CR), maximum velocity of miosis (VC), maximum velocity of mydriasis (VD) and recovery time, defined as re-dilatation to 63% frommaximum constriction (T5). The results were compared with control data measured when nothing had been inserted between the teeth. A statistically significant increase in VAS was observed starting from the 3-hour point, with themaximumvalue observed at 9 h. Significant increaseswere also seen in D1, CR, VC, VD and T5. There were positive correlations between VAS andCR andVC and evenVD. Our results show that diurnal variations in the autonomic nervous system affected the pain caused by tooth movement, and we found that such pain had an inhibitory effect on parasympathetic nerves while it activated sympathetic nerves. (The Autonomic Nervous System, 50: 306-312, 2013).

Currently, there are intensive efforts to identify and develop imaging methods to characterize and grade tumors with respect to angiogenesis. Angiogenesis is essential for tumor growth and metastases and is mediated by signaling molecules elaborated by tumors and tumor-associated inflammatory cells. Vascular endothelial growth factor (VEGF) is one of those angiogenic factors considered to play a key role in the vascularization of both normal and neoplastic tissue. VEGF is a potent and specific mitogen for endothelial cells and stimulates the full cascade of events required for angiogenesis. The VEGF polypeptide is simultaneously a vascular permeability factor (VPF) having been shown to increase the permeability of microvessels to macromolecular solutes, including serum proteins, with a potency approximating 50,000 times that of histamine. Reported studies have demonstrated that systemic administration of anti-VEGF monoclonal antibody can inhibit the growth of tumor xenografts, reduce the rate of tumor metastases, reduce overall tumor vascularity, and reduce the permeability to macromolecular solutes of tumor microvessels. However, the macromolecular permeability response to anti-VEGF antibody has been demonstrated in xenografts from tumor types arising outside the central nervous system (CNS). Similar observations may or may not extend to CNS tumors. Furthermore, the CNS has unique vascular characteristics resulting in a relatively impermeable brain/blood barrier, at least for normal neural tissue. Accordingly, macromolecular contrast media that might be well suited for estimating tumor hyperpermeability in non-neural tissues may not be necessary or well suited for CNS evaluations, and vice versa. If shown feasible in an orthotopic glial brain tumor model, the use of quantitative dynamic MRI enhanced using a small molecular gadolinium contrast agent could be applied immediately to clinical testing of antiangiogenesis drugs and to the routine evaluation of patients.