Predictors of Cerebral Aneurysm Rupture after Coil Embolization: Single-Center Experience with Recanalized Aneurysms.

BACKGROUND AND PURPOSE: Recanalization after coil embolization is widely studied. However, there are limited data on how recanalized aneurysms rupture. Herein, we describe our experience with the rupture of recanalized aneurysms and discuss the type of recanalized aneurysms at greatest rupture risk. MATERIALS AND METHODS: A total of 426 unruptured aneurysms and 169 ruptured aneurysms underwent coil embolization in our institution between January 2009 and December 2017. Recanalization occurred in 38 (8.9%) of 426 unruptured aneurysms (unruptured group) and 37 (21.9%) of 169 ruptured aneurysms (ruptured group). The Modified Raymond-Roy classification on DSA was used to categorize the recanalization type. Follow-up DSA was scheduled until 6 months after treatment, and follow-up MRA was scheduled yearly. If recanalization was suspected on MRA, DSA was performed. RESULTS: In the unruptured group, the median follow-up term was 74.0 months. Retreatment for recanalization was performed in 18 aneurysms. Four of 20 untreated recanalized aneurysms (0.94% of total coiled aneurysms) ruptured. In untreated recanalized aneurysms, class IIIb aneurysms ruptured significantly more frequently than class II and IIIa (P = .025). In the ruptured group, the median follow-up term was 28.0 months. Retreatment for recanalization was performed in 16 aneurysms. Four of 21 untreated recanalized aneurysms (2.37% of total coiled aneurysms) ruptured. Class IIIb aneurysms ruptured significantly more frequently than class II and IIIa (P = .02). CONCLUSIONS: The types of recanalization after coil embolization may be predictors of rupture. Coiled aneurysms with class IIIb recanalization should undergo early retreatment because of an increased rupture risk.

Consistent increase in the prevalence and female ratio of multiple sclerosis over 15 years in northern Japan.

BACKGROUND AND PURPOSE: The prevalence of multiple sclerosis (MS) is considered to be lower in East Asia than in Western countries. An increasing trend has been reported globally for the prevalence of MS. We investigated the changes in the prevalence and clinical characteristics of MS in the Tokachi province of Hokkaido, northern Japan from 2001 to 2016. METHODS: Prevalence was determined on 31 March 2016. Data-processing sheets were collected from all MS-related institutions in Tokachi province. We applied Poser's diagnostic criteria for MS as used in our previous three studies. Cases of neuromyelitis optica spectrum disorders were excluded. RESULTS: In 2016, the crude MS prevalence was 18.6/100 000 (95% confidence interval, 14.3-23.8) in northern Japan. Over the last 15 years, the prevalence of MS in the same area was 8.1, 12.6 and 16.2 in 2001, 2006 and 2011, respectively. The female:male ratio was 3.57, which increased from 2.63 in 2001. The ratios of primary progressive, relapsing-remitting and secondary progressive MS types were 2%, 84% and 14%, respectively. CONCLUSION: Our results demonstrated a consistent increase in MS prevalence among the northern Japanese population, particularly in females, and relatively lower rates of progressive MS in northern Japan than in Western countries.

Immunohistochemical detection of meconium in the fetal membrane, placenta and umbilical cord.

OBJECTIVE: To develop the immunohistochemistry specific for meconium in the placenta, fetal membrane and umbilical cord. STUDY DESIGN: We previously reported the specific presence of zinc coproporphyrin I (ZnCP-I) in human meconium and demonstrated the possible diagnostic use of an elevation in maternal plasma ZnCP-I levels in cases of amniotic fluid embolism. In this study, we developed a new specific monoclonal antibody for ZnCP-I and applied it to the immunostaining of meconium in the placenta, fetal membrane, and umbilical cord. RESULTS: Immunoreactivity of ZnCP-I clearly and specifically identified meconium in the placenta, fetal membrane, and umbilical cord. It was especially useful in cases of severe chorioamnionitis to detect meconium in the macrophages surrounded by numerous neutrophils. In more than half of the cases, meconium was detected in clear amniotic fluid at delivery, suggesting previous exposure. CONCLUSIONS: Immunohistochemical detection of ZnCP-I is a highly sensitive histological diagnosis of meconium.

The effect of Assertive Community Treatment in Japan.

OBJECTIVE: The aim of this study was to evaluate the effects of the Assertive Community Treatment (ACT) program in a Japanese mental health service setting. METHOD: This study was a randomized controlled trial. ACT was the intervention condition (n = 59), and the usual hospital-based rehabilitation program was the control condition (n = 59). Outcome indicators include in-patient days, psychiatric symptoms, social functioning, quality of life, and client satisfaction. The follow-up period was 12 months after the intervention. RESULTS: We found a significant reduction of in-patient days for the ACT group demonstrated by t-test (t = 2.33, P = 0.02). However, the results of ancova did not show significant differences for in-patient days between the two groups (F = 1.85, P = 0.18). The depression score for Brief Psychiatric Rating Scale for the ACT group was significantly lower than the control group at the 12-month follow-up assessment (F = 5.57, P = 0.03). According to the t-test, the ACT group had a higher client satisfaction than the control group (t = 2.08, P = 0.05). CONCLUSION: We concluded that ACT had a positive influence, as evidenced by a reduction of in-patient days, lower depressive symptoms, and higher client satisfaction.

The waved with open eyelids (woe) locus is a hypomorphic mouse mutation in Adam17.

The waved with open eyes (woe) locus is a spontaneous recessive mouse mutation that exhibits wavy fur, eyelids open at birth, and enlarged heart and esophagus. In this study, we confirmed the previously identified woe phenotypes and additionally identified anterior eye segment defects, absence of the meibomian glands, and defects in the semilunar cardiac valves. Positional cloning identified a C794T substitution in the Adam17 gene that ablates a putative exonic splicing enhancer (ESE) sequence in exon 7 resulting in aberrant Adam17 splicing. The predominant woe transcript, Adam17(Delta)(exon7), lacks exon 7 resulting in an in-frame deletion of 90 bp and a putative Adam17(Delta252-281) protein lacking residues 252-281 from the metalloprotease domain. Western blot analysis in woe identified only the precursor form of Adam17(Delta252-281) protein. Absence of cleavage of the prodomain renders Adam17(Delta252-281) functionally inactive; however, constitutive and stimulated shedding of Adam17 substrates was detected in woe at significantly reduced levels. This residual Adam17 shedding activity in woe most likely originates from full-length Adam17(T265M) encoded by the Adam17(C794T) transcript identified expressed at severely reduced levels. These results show that even small amounts of functional Adam17 allow woe mice to survive into adulthood. In contrast to Adam17(-/-) mice that die at birth, the viability of woe mice provides an excellent opportunity for studying the role of Adam17 throughout postnatal development and homeostasis.

GRIP1 enhances estrogen receptor alpha-dependent extracellular matrix gene expression in chondrogenic cells.

OBJECTIVE: The role of postmenopause on the pathogenesis of cartilage degeneration has been an open question. We assessed cartilage degeneration in estrogen receptor (ER)alpha null mice and examined the role of glucocorticoid receptor-interacting protein 1 (GRIP1) in the ERalpha-dependent transcription of a type II collagen gene (col2a1) with special reference to a crosstalk with the transforming growth factor (TGF)-beta signaling pathway. METHODS: The vertebral cartilaginous endplate from female ERalpha null mice was subjected to histological analyses. Col2a1 expression of primary chondrocytes (PCs) obtained from ERalpha null mice after 17beta-estradiol (E(2)) and TGF-beta1 stimulation was examined by reverse transcription polymerase chain reaction (RT-PCR). Estrogen response element (ERE) or col2a1 promoter-enhancer luciferase reporter system was used to investigate the crosstalk among ERalpha, GRIP1, and MKK6. Col2a1 expression and glycosaminoglycan (GAG) content were measured in ATDC5 cells treated with GRIP1 small interfering RNA (siRNA). RESULTS: ERalpha deficiency clearly accelerated impairment of the vertebral cartilaginous endplate. E(2) and TGF-beta1 stimulation increased col2a1 expression in PC from wild-type mice, but not that from ERalpha null mice. The same stimulation increased the col2a1 promoter-enhancer reporter activity, and the elevated activity was decreased by dominant-negative ERalpha and p38 mitogen-activated protein kinase (MAPK) inhibitor. GRIP1 increased the E(2)-dependent ERE activation in the presence of ERalpha and constitutive-active MKK6. GRIP1 siRNA repressed col2a1 expression and GAG production in ATDC5 cells. CONCLUSIONS: Crosstalks between ERalpha/GRIP1 and TGF-beta/MKK6/p38 MAPK pathway have protective roles on cartilage metabolism via regulating the extracellular matrices expression. The finding may lead to the development of a novel therapeutic approach for cartilage degeneration.

Molecular analysis of non-syndromic preaxial polydactyly: preaxial polydactyly type-IV and preaxial polydactyly type-I.

Human GLI3 gene mutations have been identified in several phenotypes of digital abnormality such as Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type-IV (PPD-IV) and postaxial polydactyly. However, the different phenotypes resulting from GLI3 mutations have not yet been properly defined. We have experienced two types of digital abnormality without other complicating developmental defects; a family with foot PPD-IV with syndactyly of the third and fourth fingers, and four sporadic cases with biphalangeal thumb polydactyly (PPD-I). The genes responsible for syndactyly of the third and fourth fingers (syndactyly type-I) and PPD-I have not yet been identified; we therefore examined the involvement of the GLI3 gene in these subtypes of digital abnormality. We found a non-sense mutation in the GLI3 gene in the family with foot PPD-IV accompanied with hand syndactyly of the third and fourth fingers, but no mutations were detected in the GLI3 gene in the four other cases with PPD-I alone. Thus, the phenotype of foot PPD-IV accompanied with hand syndactyly of the third and fourth fingers may result from a GLI3 mutation, whereas the PPD-I phenotype alone is not caused by GLI3 gene defect. These results will help to define the phenotypic spectrum of GLI3 morphopathies, which have been recently proposed.

Short-term complications of retrograde transvenous obliteration of gastric varices in patients with portal hypertension: effects of obliteration of major portosystemic shunts.

The type, incidence, and severity of complications of balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices should be precisely estimated. Complications were evaluated in 38 patients who had fundic gastric varices and 43 B-RTO procedures during injection of ethanolamine oleate (phase 1), within 4 h after injection (phase 2), 24 h after injection (phase 3), and from 24 h to 10 days after injection (phase 4). Endoscopic evaluation at 8 weeks showed resolution of gastric varices in 35 of 38 patients (92%) and smaller varices in the remaining three (8%). B-RTO caused transient hypertension in 35% of patients, hemoglobinuria in 49%, and fever in 33% during phases 1, 2, and 3, respectively. Pleural effusion, pulmonary infarction, ascites, gastric ulcers with unique appearance, localized mosaic-like change of gastric mucosa, and hemorrhagic portal hypertensive gastropathy were noted in phase 4. There were no fatalities. Lactate dehydrogenase, aspartate aminotransferase, and bilirubin increased on day 1. Each datum was retrieved within 7 days. The severity of lactate dehydrogenase elevation correlated significantly with the volume of infused ethanolamine oleate. Thus, B-RTO is a safe and effective management of fundic varices. However, short-term hemodynamic change after B-RTO may cause gastric mucosal damage. Pulmonary infarction and pleural effusion are potential complications.

Production of L-lactic acid from a mixture of xylose and glucose by co-cultivation of lactic acid bacteria.

The production of optically pure lactic acid in a high yield from xylose or a mixture of xylose and glucose, which is a model hydrolysate of lignocellulose, is described. In a single cultivation, Enterococcus casseliflavus produced 38 g/l of lactic acid with an optical purity of 96% enantiomeric excess (ee) and 6.4 g/l of acetic acid from 50 g/l of xylose when MRS medium was used. When a mixture of 50 g/l of xylose and 100 g/l of glucose was used as the carbon source in a cultivation of E. casseliflavus alone, glucose was converted to lactic acid in the early phase of the cultivation but xylose was hardly consumed. In a co-cultivation where E. casseliflavus and Lactobacillus casei specific for glucose were simultaneously inoculated, little or no lactic acid was produced after the glucose was almost consumed. A co-cultivation with two-stage inoculation (in which E. casseliflavus was added at a cultivation time of 40 h after L. casei cells were inoculated) resulted in complete consumption of 50 g/l of xylose and 100 g/l of glucose. In the co-cultivation, 95 g/l of lactic acid with a high optical purity of 96% ee was obtained at 192 h. Such a co-cultivation using two microorganisms specific for each sugar is considered to be one promising cultivation technique for the efficient production of lactic acid from a sugar mixture derived from lignocellulose.

Mandibular reconstruction using a vascularised fibula osteocutaneous flap in a patient with pyknodysostosis.

We present the first successful report of mandibular reconstruction using a free fibula osteocutaneous flap in a patient with pyknodysostosis. The patient had recurrent refractory osteomyelitis of the mandible, which was initially treated with resection and reconstruction using an AO plate. Recurrent fistula formation with loosening of the plate was treated by radical re-excision and reconstruction with a free fibula flap. The postoperative course was uneventful; at 14 months the bony union was almost complete, without resorption or atrophy of the grafted fibula on radiography.

Two innovations of the star-flap technique for nipple reconstruction.

Two innovations of the star-flap technique for nipple reconstruction are described. A combination of the star-flap technique and a contralateral nipple graft is indicated in patients with a large nipple and small areola on the contralateral side. It provides sufficient volume for the new nipple and improves the shape of the donor nipple. A combination of the star-flap technique and a banked costal-cartilage graft offers better nipple contour and projection than the conventional star-flap technique. Preparation of the cartilage graft is easy and does not result in additional scarring; the nipple projection can be expected to be maintained over a long period.

Flexibility and nucleation in sickle hemoglobin.

We have studied the self-assembly of Hemoglobin C-Harlem (HbC-Harlem), a double mutant of hemoglobin that possesses the beta6 Glu-->Val mutation of sickle hemoglobin (HbS) plus beta73 Asp-->Asn. By electron microscopy we find it forms crystals, rather than the wrapped multistranded fibers seen in HbS. Fourier transforms of the crystals yield unit cell parameters indistinguishable from crystals of HbS. Differential interference contrast (DIC) microscopy and birefringence also show crystal formation rather than the polymers or domains seen for HbS, while the growth patterns showed radiating crystal structures rather than simple linear crystalline forms. The solubility of the assembly was measured using a photolytic micromethod over a temperature range of 17-31 degrees C in 0.15 M phosphate buffer and found to be essentially the same as that of fibers of HbS. The assembly kinetics were observed by photolysis of the carbon monoxide derivative, and the mass of assembled hemoglobin was found to grow exponentially, with onset times that were stochastically distributed for small volumes. The stochastic onset of assembly showed strong concentration dependence, similar to but slightly greater than that seen in sickle hemoglobin nucleation. These observations suggest that like HbS, HbC-Harlem assembly proceeds by a homogeneous nucleation process, followed by heterogeneous nucleation. However, relative to HbS, both homogeneous and heterogeneous nucleation are suppressed by almost 11 orders of magnitude. The slowness of nucleation can be reconciled with the similarity of the solubility to HbS by an increase in contact energy coupled with a decrease in vibrational entropy recovered on assembly. This also explains the linearity of the double-strands, and agrees with the chemical nature of the structural replacement.

Repulsive charge mechanism serve to maintain lumens and cavities. An histochemical study of rat serosa and kidney.

The free surface of the rat peritoneum was covered with a rich negative-charged substance which is distinctly stained with cationic colloidal iron (pH 1.5). Neuraminidase digestion erased this iron stain. Treatment with Limax flavus agglutinin (LFA), which has specific affinity to sialic acid, interferred with iron staining on the serosal surface. Transmission electron microscopy of the peritoneal samples stained with colloidal iron showed that colloidal particles were deposited on the free surface of the mesothelial cells. At pH 1.5, the colloidal particles aggregated in a dotted fashion; in those stained at pH 7.0, the particles arranged in fine strands (100-300 nm in length). This difference may occur as a structural transformation due to pH level changes. The string like structure seemed to correspond well to membrane associated sialomucin. The urinary surface of the rat glomerular podocytes possessed negatively charged sites detectable with cationic colloidal iron even at pH 1.5. Neuraminidase and LFA treatments erased iron staining. Substance containing sialic acid such as podocalyxin on the podocyte surface may be stained. This study shows that negatively charged sites of the substance covering the free surface of these regions repulse each other to maintain the serosal cavities or the podocyte end-feet slits.

Glutamyl-gamma-boronate inhibitors of bacterial Glu-tRNA(Gln) amidotransferase.

Analogues of glutamyl-gamma-boronate (1) were synthesized as mechanism-based inhibitors of bacterial Glu-tRNA(Gln) amidotransferase (Glu-AdT) and were designed to engage a putative catalytic serine nucleophile required for the glutaminase activity of the enzyme. Although 1 provides potent enzyme inhibition, structure-activity studies revealed a narrow range of tolerated chemical changes that maintained activity. Nonetheless, growth inhibition of organisms that require Glu-AdT by the most potent enzyme inhibitors appears to validate mechanism-based inhibitor design of Glu-AdT as an approach to antimicrobial development.

The relationship of oxidative DNA damage marker 8-hydroxydeoxyguanosine and glycoxidative damage marker pentosidine.

OBJECTIVES: 8-hydroxydeoxyguanosine (8-OHdG) is a biomarker of oxidative DNA damage. Pentosidine is a biomarker of glycoxidation reaction. In this study, we investigated relationships among 8-OHdG, pentosidine and age. DESIGN AND METHODS: We determined the urinary concentrations of 8-OHdG and pentosidine in adults with mild hypercholesterolemia or/and mild hypertension (hypercholesterolemia group, n = 31; hypertension group, n = 25; hypercholesterolemia and hypertension group, n = 7). RESULTS: The strength of the relationship between 8-OHdG and age was the same as that between pentosidine and age (the correlation coefficient between 8-OHdG and age was 0.33, pentosidine and age was 0.37). In addition, there was a positive and significant correlation between 8-OHdG and pentosidine. On the other hand, mean values of 8-OHdG and pentosidine showed no significant difference among the three groups. CONCLUSION: The results of the present study indicate that both 8-OHdG and pentosidine levels increase similarly in degenerative pathologic conditions.

Pharmacological properties of R-755, a novel acyl-CoA:cholesterol acyltransferase inhibitor, in cholesterol-fed rats, hamsters and rabbits.

R-755 (N-(2,6-diethylphenyl)-N'-[3-(2-methylphenyl)-6,7-dihydro-5H-cyclopenta[f[l]benzothiophen-2-yl]urea), a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, has been characterized in vitro, ex vivo and in vivo. R-755 potently inhibited ACAT activities, with IC50 values from 2.5 to 64 nM, in rabbit intestinal microsomes and several cell lines (CaCo-2, THP-1 and J774A.1 cells). R-755 reduced serum cholesterol and triglyceride levels and liver cholesterol contents in cholesterol-fed rats, hamsters and rabbits. Rabbits were fed a high cholesterol diet for 2 weeks and further fed the same diet containing R-755 for 2 weeks. R-755 dose-dependently reduced cholesterol content and ACAT activity in the aorta. When phorbol 12-myristate 13-acetate-treated THP-1 and J774A.1 cells were incubated in the medium containing 20% of serum from rats administered R-755, the ACAT activities of the cells were inhibited. Rabbits were fed a high cholesterol diet for 8 weeks to establish aortic atherosclerosis and then fed a normal diet with or without R-755 for 8 weeks. R-755 dose-dependently reduced the surface area with atherosclerotic involvement and cholesterol contents in the aorta, although plasma cholesterol level did not differ from that in the control group. These results suggest that R-755 is a potent hypolipidemic agent and has a direct antiatherosclerotic activity at the arterial wall.