Hyposalivation in autoimmune diseases

We have investigated the prevalence of dry mouth among patients with autoimmune diseases other than Sjögren’s syndrome. One hundred and forty-four patients, excluding patients with primary Sjögren’s syndrome, were enrolled in this study. The volume of saliva secreted was measured with the screening technique for estimation of salivary flow, which uses a filter paper for diagnosing dry mouth. Disturbed salivary secretion was observed in 84 (58.3 %) of the 144 patients. In the case of patients free of Sjögren’s syndrome, the prevalence of disturbed salivary secretion differed significantly among the disease groups (P < 0.05), with the prevalence being over 50 % in all disease groups other than the rheumatoid arthritis group and the highest in the systemic sclerosis group. There was significant positive correlation between the number of colored spots and oral visual analog scale score (r = 0.45, P < 0.0001). Autoimmune diseases can be accompanied by salivary gland dysfunction, regardless of the presence/absence of complication by Sjögren’s syndrome. In the present study, the screening technique for estimation of salivary flow, which uses a filter paper for diagnosing dry mouth, was shown to be a useful means of detecting salivary gland dysfunction.     

Long-term changes in neointimal hyperplasia following implantation of bare metal stents assessed by integrated backscatter intravascular ultrasound

In-stent restenosis (ISR) is a common phenomenon with bare metal stents (BMSs) in the early stage after implantation. However, ISR occurs at a lower rate with long time after BMS implantation. We assessed changes over time in neointimal hyperplasia following BMS implantation using integrated backscatter intravascular ultrasound (IB-IUVS). Thirty-six patients who received target lesion revascularization (TLR) to treat ISR were classified according to the duration of the interval between stent implantation and TLR: the early group (within first year n = 25) and the VL group (very late ISR ≥5 years, n = 11). IB-IUVS was used to evaluate within-stent sites from the proximal to the distal edge of the stent. IB-IVUS color maps were then constructed by tracing the stent struts and vessel lumen. Neointimal tissue was classified as high-IB (IB <?29 dB; a representative cord of calcification), middle-IB (?49 dB ≤ IB < ?29 dB; fibrosis), or low-IB (?49 dB ≤ IB; lipid pool). We compared percent (%) volume, average %area of cross-sectional area (CSA), and %area of minimum CSA of each component between the groups. There were no significant differences in %volume, average %area of CSA, or %area of minimum CSA for the high-IB component between groups. The %low-IB components were 20.0 ± 8.8 % for volume, 20.1 ± 8.9 % for mean CSA, and 17.6 ± 8.5 % for minimum CSA in the early group. On the other hand, in the VL group, the %low-IB components were significantly increased to 31.8 ± 7.9 % for volume (p < 0.01 vs. the early group), 31.2 ± 7.6 % for mean CSA (p < 0.01 vs. the early group), and 33.1 ± 12.3 % for minimum CSA (p < 0.01 vs. the early group). By contrast, the %middle-IB component showed a reduction in extended time, with %volume of the middle-IB decreasing from 78.3 ± 8.1 to 66.4 ± 7.1 %, average mean %area of CSA from 78.2 ± 8.2 to 66.9 ± 6.9 %, and % area of minimum CSA from 80.7 ± 7.9 to 65.5 ± 11.4 % (p < 0.01;. the early vs. the VL group). Our results suggest that in-stent neointimal tissues developing over time consist of an increased low-IB component and a decreased middle-IB component and may contribute an increased of lipidemic component and a decreased of fibrotic component.     

Validation of NIH consensus criteria for diagnosis and severity-grading of chronic graft-versus-host disease

To validate the National Institutes of Health (NIH) consensus criteria for chronic GVHD, we retrospectively reviewed 143 patients who developed GVHD later than 100 days after allogeneic hematopoietic stem cell transplantation. Their GVHD was reclassified and the severity was graded according to the criteria. Only four patients (2.8 %) could not be reclassified into any type of GVHD. In the remaining 139 patients, reclassified subtypes were late acute GVHD in 52 patients (37.4 %), classic chronic GVHD in 33 (23.7 %), and overlap syndrome in 54 (38.8 %). Of 87 patients with classic chronic GVHD or overlap syndrome, the severity was graded as mild in 21 patients (24 %), moderate in 53 (61 %), and severe in 13 (15 %). The proportions of moderate (70 %) and severe (20 %) disease were significantly higher in patients with overlap syndrome than those with classic chronic GVHD (46 and 6 %, respectively; P < 0.001). Univariate and multivariate analyses of subtypes and severity did not identify any significant prognostic values in any of the transplant outcomes, such as transplant-related mortality, overall survival, GVHD-specific survival, or discontinuation of systemic immunosuppressants. These findings suggest that the NIH consensus criteria are useful for classification of chronic GVHD, but have limited significance in predicting clinical outcomes. The validity of these criteria remains inconclusive, and future prospective studies will be required to refine them.     

Correlation between Depth Perception by Three-Rods Test and Stereoacuity by Distance Randot Stereotest

Background: The examination of depth perception with three-rods test, in addition to visual acuity testing, is required to obtain motor vehicle license to drive taxies and trucks, according to the Road Traffic Act in Japan. The aim of this study was to examine whether the results of the three-rods test would correlate with the results of static stereopsis tests, used in ophthalmic practice.

Methods: This study involved 54 normal subjects, 9 women and 45 men, with ages ranging from 18 to 25 (mean, 20.8) years. All had visual acuity of 0.8 or better with or without glasses or contact lenses correction and had no strabismus at the distant (5?m) or near (0.3?m) fixation. TNO Stereotest and Titmus Stereotest were examined at 40?cm while Distance Randot Stereotest was at 3?m. At three-rods test, a central rod was moved at the speed of 50?mm/sec forward and backward automatically against two laterally located fixed rods, placed inside the illuminated box. An examinee at the distance of 2.5?m observed the rods inside the box from a small viewing window and pushed a button to stop the central rod in alignment with the fixed rods. Erred distance (mm) of the central rod from the fixed rods as a mean of 4 measurements was correlated with stereoacuity in second of arc, measured by three kinds of the stereopsis tests.

Results: The erred distance of three-rods test was positively correlated with static stereoacuity at distance measured with Distance Randot Stereotest (ρ?=?0.418, p?=?0.0023, Spearman rank correlation test) and also with the other stereopsis tests at near fixation. The stereoacuity at near fixation, measured by TNO Stereotest and Titmus Stereotest, was positively correlated with each other (ρ?=?0.431, p?=?0.0017).

Conclusion: Three-rods test, examining depth perception, together with the response by eye-hand coordination, gave consistent results with distant static stereoacuity when measured with Distance Randot Stereotest.     

Crocetin,a Carotenoid from Gardenia jasminoides Ellis,Protects against Hypertension and Cerebral Thrombogenesis in Stroke‐prone Spontaneously Hypertensive Rats

Crocetin is a natural carotenoid dicarboxylic acid that is found in the fruit of Gardenia jasminoides Ellis (Cape Jasmine) and in the stamen and pistil of Crocus sativus L. (saffron). It is used worldwide as an important spice, food colorant, and herbal medicine. In the current investigation, we have examined the cardiovascular effects of crocetin using stroke‐prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs (6 weeks old) were classified into three groups: a control group and two crocetin groups (25 and 50 mg/kg/day). The animals were given crocetin for 3 weeks. Body weights in each group were not significantly different during the treatment period, but the increase in systolic blood pressures observed with age was significantly moderated by crocetin. Thrombogenesis, assessed using a He‐Ne laser technique in pial vessels, was significantly decreased. Antioxidant activity, assessed by measuring urinary 8‐hydroxy‐2′‐deoxyguanosine levels, together with urinary nitric oxide (NO) metabolite levels, was increased significantly after treatment. Acetylcholine‐induced vasodilation was measured using the aorta and indicated that endothelial function was significantly improved by crocetin. These results strongly suggest that the antihypertensive and antithrombotic effects of crocetin were related to an increase in bioavailable NO, possibly mediated by decreased inactivation of NO by reactive oxygen species. Copyright © 2014 John Wiley & Sons, Ltd.     

Molecular and clinical findings and their correlations in Silver-Russell syndrome: implications for a positive role of IGF2 in growth determination and differential imprinting regulation of the IGF2–H19 domain in bodies and placentas

Silver-Russell syndrome (SRS) is characterized by growth failure and dysmorphic features and is frequently caused by hypomethylation (epimutation) of the H19-DMR. Although molecular and clinical studies have extensively been performed for SRS patients themselves, such studies have not been carried out for placentas. We identified 20 epimutation-positive and 40 epimutation-negative Japanese SRS patients and obtained placental weight data from 12 epimutation-positive and ten epimutation-negative patients and paraffin-embedded placental tissues for molecular and histological examinations from three epimutation-positive and two epimutation-negative patients. Methylation patterns were comparable between leukocytes and placentas in both epimutation-positive and epimutation-negative patients. Epimutations resulted in virtually no IGF2 expression and biallelic slight H19 expression in the leukocytes and obviously reduced IGF2 expression of paternal origin and nearly normal H19 expression of maternal origin in the placentas. Epimutation-positive patients had characteristic body phenotype and small placentas with hypoplastic chorionic villi, and epimutation-negative patients had somewhat small placentas with hypoplastic chorionic villi or massive infarction. Furthermore, significant correlations were identified between the H19-DMR methylation index and the body and placental sizes and between the placental weight and the body size in the epimutation-positive patients, whereas such correlations were not detected for the head circumference. These results suggest (1) characteristic phenotype and reduced IGF2 expression in the epimutation-positive placentas; (2) similarities and differences in the epigenetic control of the IGF2–H19 domain between leukocytes and placentas; (3) a positive role of the IGF2 expression level, as reflected by the methylation index, in the determination of body and placental growth in epimutation-positive patients, except for the brain where IGF2 is expressed biallelically; (4) involvement of placental dysfunction in prenatal growth failure; and (5) relevance of both (epi)genetic factor(s) and environmental factor(s) to SRS in epimutation-negative patients. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.