Reduced Leukoaraiosis, Noncardiac Embolic Stroke Etiology, and Shorter Thrombus Length Indicate Good Leptomeningeal Collateral Flow in Embolic Large-Vessel Occlusion.

BACKGROUND AND PURPOSE: Acute leptomeningeal collateral flow is vital for maintaining perfusion to penumbral tissue in acute ischemic stroke caused by large-vessel occlusion. In this study, we aimed to investigate the clinically available indicators of leptomeningeal collateral variability in embolic large-vessel occlusion. MATERIALS AND METHODS: Among prospectively registered consecutive patients with acute embolic anterior circulation large-vessel occlusion treated with thrombectomy, we analyzed 108 patients admitted from January 2015 to December 2019 who underwent evaluation of leptomeningeal collateral status on pretreatment CTA. Clinical characteristics, extent of leukoaraiosis on MR imaging, embolic stroke subtype, time of imaging, occlusive thrombus characteristics, presenting stroke severity, and clinical outcome were collected. The clinical indicators of good collateral status (>50% collateral filling of the occluded territory) were analyzed using multivariate logistic regression analysis. RESULTS: Good collateral status was present in 67 patients (62%) and associated with independent functional outcomes at 3 months. Reduced leukoaraiosis (total Fazekas score, 0-2) was positively related to good collateral status (OR, 9.57; 95% CI, 2.49-47.75), while the cardioembolic stroke mechanism was inversely related to good collateral status (OR, 0.17; 95% CI, 0.02-0.87). In 82 patients with cardioembolic stroke, shorter thrombus length (OR, 0.91 per millimeter increase; 95% CI, 0.82-0.99) and reduced leukoaraiosis (OR, 5.79; 95% CI, 1.40-29.61) were independently related to good collateral status. CONCLUSIONS: Among patients with embolic large-vessel occlusion, reduced leukoaraiosis, noncardiac embolism mechanisms including embolisms of arterial or undetermined origin, and shorter thrombus length in cardioembolism are indicators of good collateral flow.

Loss of Function of Evc2 in Dental Mesenchyme Leads to Hypomorphic Enamel.

Ellis-van Creveld (EvC) syndrome is an autosomal-recessive skeletal dysplasia, characterized by short stature and postaxial polydactyly. A series of dental abnormalities, including hypomorphic enamel formation, has been reported in patients with EvC. Despite previous studies that attempted to uncover the mechanism leading to abnormal tooth development, little is known regarding how hypomorphic enamel is formed in patients with EvC. In the current study, using Evc2/ Limbin mutant mice we recently generated, we analyzed enamel formation in the mouse incisor. Consistent with symptoms in human patients, we observed that Evc2 mutant mice had smaller incisors with enamel hypoplasia. Histologic observations coupled with ameloblast marker analyses suggested that Evc2 mutant preameloblasts were capable of differentiating to secretory ameloblasts; this process, however, was apparently delayed, due to delayed odontoblast differentiation, mediated by a limited number of dental mesenchymal stem cells in Evc2 mutant mice. This concept was further supported by the observation that dental mesenchymal-specific deletion of Evc2 phenocopied the tooth abnormalities in Evc2 mutants. Overall, our findings suggest that mutations in Evc2 affect dental mesenchymal stem cell homeostasis, which further leads to hypomorphic enamel formation.

The 'when' and 'where' of semantic coding in the anterior temporal lobe: Temporal representational similarity analysis of electrocorticogram data.

Electrocorticograms (ECoG) provide a unique opportunity to monitor neural activity directly at the cortical surface. Ten patients with subdural electrodes covering ventral and lateral anterior temporal regions (ATL) performed a picture naming task. Temporal representational similarity analysis (RSA) was used, for the first time, to compare spatio-temporal neural patterns from the ATL surface with pre-defined theoretical models. The results indicate that the neural activity in the ventral subregion of the ATL codes semantic representations from 250 msec after picture onset. The observed activation similarity was not related to the visual similarity of the pictures or the phonological similarity of their names. In keeping with convergent evidence for the importance of the ATL in semantic processing, these results provide the first direct evidence of semantic coding from the surface of the ventral ATL and its time-course.

MR imaging-based localized intra-arterial thrombolysis assisted by mechanical clot disruption for acute ischemic stroke due to middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: LIT-MCD is used in our institution for acute stroke due to MCA occlusion, with the goal of reducing symptomatic intracranial hemorrhage by maintaining recanalization of the occluded vessels. The purpose of the study was to investigate the safety and efficacy of LIT-MCD and to identify factors associated with a poor outcome in patients undergoing this procedure. MATERIALS AND METHODS: LIT-MCD for MCA occlusion was performed in 90 of 1907 consecutive patients with acute stroke admitted to our institution. Radiographic data and clinical outcome were evaluated in the 90 patients, and factors predictive of a poor outcome (3-month mRS score, 3-6) were investigated by multivariate analysis. RESULTS: Recanalization was achieved in 73 of the 90 patients (81%); symptomatic intracranial hemorrhage occurred in 7 (8%); procedure-related complications, in 9 (10%); and a favorable clinical outcome (3-month mRS score, 0-2), in 48 (53%). A high baseline NIHSS score (≥20), a low preprocedural ASPECTS on MR imaging (≤7), proximal M1 occlusion (in the horizontal segment of the MCA at or proximal to the lenticulostriate arteries), and no recanalization were significant predictors of a poor clinical outcome. CONCLUSIONS: LIT-MCD is a safe and effective treatment for acute stroke due to MCA occlusion. However, further intervention is needed to improve the outcome of patients with proximal M1 occlusion.

A missense mutation (p.Leu2153His) of the factor VIII gene causes cattle haemophilia A.

Two cases of hereditary bleeding disorder diagnosed as haemophilia A were recently observed in Japanese Brown cattle. We sequenced the entire coding region of the factor VIII gene of the affected animals to find a causative mutation. A nucleotide substitution of T to A resulting in an amino acid substitution of leucine to histidine (p.Leu2153His) was identified in a highly conserved residue in the C1 domain of factor VIII. Genotyping of 254 normal animals including the pedigree of the affected animals and randomly sampled animals of different breeds confirmed that the substitution is the causative mutation of cattle haemophilia A.

Linkage mapping of the locus responsible for forelimb-girdle muscular anomaly of Japanese black cattle on bovine chromosome 26.

Forelimb-girdle muscular anomaly is an autosomal recessive disorder of Japanese black cattle characterized by tremor, astasia and abnormal shape of the shoulders. Pathological examination of affected animals reveals hypoplasia of forelimb-girdle muscles with reduced diameter of muscle fibres. To identify the gene responsible for this disorder, we performed linkage mapping of the disorder locus using an inbred pedigree including a great-grand sire, a grand sire, a sire and 26 affected calves obtained from a herd of Japanese black cattle. Two hundred and fifty-eight microsatellite markers distributed across the genome were genotyped across the pedigree. Four markers on the middle region of bovine chromosome 26 showed significant linkage with the disorder locus. Haplotype analysis using additional markers in this region refined the critical region of the disorder locus to a 3.5-Mb interval on BTA26 between BM4505 and MOK2602. Comparative mapping data revealed several potential candidate genes for the disorder, including NRAP, PDZD8 and HSPA12A, which are associated with muscular function.

Transluminal angioplasty and stenting for intracranial vertebrobasilar occlusive lesions in acute stroke patients.

BACKGROUND AND PURPOSE: The clinical outcome is often poor in acute stroke patients with a serious neurological status due to occlusive lesions of the intracranial vertebral and/or basilar artery (IVBA). The purpose of this study was to investigate retrospectively the clinical features and outcome of acute stroke patients who underwent transluminal angioplasty and/or stenting (TAS) for occlusive lesions of the IVBA and to clarify the prerequisites for improvement of outcome. MATERIALS AND METHODS: Of 1690 consecutive acute ischemic stroke patients admitted to our institution, TAS for occlusive lesions of the IVBA was performed within 7 days after stroke onset in 28 patients. We classified these patients into 2 groups, those with total occlusion (occlusion group) and those with a high-grade stenosis (stenosis group), and compared the preprocedural neurologic status (severe: National Institutes of Health Stroke Scale >20), the rate of technical success, major procedure-related complications, subacute occlusion of the treated vessel, and favorable clinical outcome (0-2 points on a 3-month modified Rankin Scale) between the 2 groups. RESULTS: In the occlusion group (n = 16) and stenosis group (n = 12), a severe preprocedural neurologic status was seen in 13 and 1 patients, respectively (81% versus 8%; P = .0001); technical success was achieved in 13 and 11 patients, respectively (81% versus 92%; P value not significant [NS]); complications occurred in 6 and 0 patients, respectively (38% versus 0%; P < .05); subacute occlusion was seen in 4 and 1 patients, respectively (25% versus 8%; P = NS); and a favorable clinical outcome was obtained in 3 and 9 patients, respectively (19% versus 75%; P < .01). CONCLUSION: The clinical outcome of patients who underwent TAS for total occlusion of the IVBA was poor. Improvement of outcome requires reduction of procedure-related complications and subacute occlusion.

Revascularization procedure mainly by suction thrombectomy for acute cervical carotid occlusion.

SUMMARY: In many cases, the prognosis for acute cervical carotid artery occlusion is poor. However, a standard treatment for the acute stage is not yet established. We report here the results of eight consecutive patients (mean age 71.5 years old) in which revascularization mainly by suction thrombectomy was performed under proximal protection during the acute phase. The occlusion sites were the intracranial internal carotid artery in five patients, tandem lesions of the internal carotid origin and intracranial vessel in two patients, and the common carotid artery in one patient. In addition, the subjects who received the treatment had an extent of infarction in MRI/DWI that was 1/3 or less of the internal carotid artery territory. The mean time from the onset to treatment commencement was 7.25 hours (2-28 hours). For the endovascular treatment, a guiding catheter with a balloon was used for proximal protection of the carotid artery. Revascularization was performed mainly by suction thrombectomy, and if a stenosed lesion was observed, PTA/stenting was added. Local fibrinolysis was not performed in combination with the above procedure. The treatment results were complete recanalization in three patients and partial recanalization in three patients. However, recanalization was not achieved in two patients. No hyperfusion syndrome or hemorrhagic infarction was observed postoperatively. All four patients in whom thrombi were successfully aspirated had occlusions proximal to the ophthalmic artery branch. In three of these four patients, complete recanalization was achieved. The revascularization procedure using suction thrombectomy under proximal protection was considered effective against the acute cervical carotid occlusions, in particular, those proximal to the ophthalmic artery branch.

Congenital multiple ocular defects with falciform retinal folds among Japanese black cattle.

To clarify the morphologic features of the ocular disease recently occurring among Japanese Black cattle in southern Kyushu, 6 globes from 3 Japanese Black cattle, between 11 and 20 months old (cow Nos. 1 to 3), were pathologically examined. Cow Nos. 1 and 2 were sired by the same Japanese Black bull, and cow No. 3 was sired by the ancestor (sire) of the former bull. The ocular lesions were pathologically similar to each other, except for the left eye of cow No. 1. The ocular lesions of 5 globes were characterized by microphthalmia, hypoplasia, and/or dysplasia of the lenses; persistence of the primary vitreous; and retinal dysplasia with total nonattachment. The left globe from cow No. 1 had no lens and severe hypoplasia and nonattachment of the retina. Because dysplastic retinal lesions that formed crescentic folds and a central column were the most characteristic features of the eyes, the falciform retinal fold with congenital nonattachment was the most likely disease entity. Although the cause of the ocular disease could not be clarified with the present study, an inherited ocular defect of the bull and its ancestor was suspected.

Carbohydrate metabolism genes and pathways in insects: insights from the honey bee genome.

Carbohydrate-metabolizing enzymes may have particularly interesting roles in the honey bee, Apis mellifera, because this social insect has an extremely carbohydrate-rich diet, and nutrition plays important roles in caste determination and socially mediated behavioural plasticity. We annotated a total of 174 genes encoding carbohydrate-metabolizing enzymes and 28 genes encoding lipid-metabolizing enzymes, based on orthology to their counterparts in the fly, Drosophila melanogaster, and the mosquito, Anopheles gambiae. We found that the number of genes for carbohydrate metabolism appears to be more evolutionarily labile than for lipid metabolism. In particular, we identified striking changes in gene number or genomic organization for genes encoding glycolytic enzymes, cellulase, glucose oxidase and glucose dehydrogenases, glucose-methanol-choline (GMC) oxidoreductases, fucosyltransferases, and lysozymes.

Clot removal therapy by aspiration and extraction for acute embolic carotid occlusion.

BACKGROUND AND PURPOSE: The purpose of our retrospective study was to investigate the feasibility, safety, and efficacy of clot removal therapy by aspiration and extraction for patients with acute stroke with embolic internal carotid artery (ICA) occlusion. METHODS: Of 814 consecutive patients with acute ischemic stroke admitted to our institution from March 2003 to April 2005, clot removal therapy was performed for 14. Inclusion criteria were patients (1) presenting within 6 hours of onset of cardioembolic stroke, (2) with serious neurologic symptoms defined by a National Institutes of Health Stroke Scale (NIHSS) score of at least 11, (3) without extensive high signal intensity on diffusion-weighted MR images but with decreased ipsilateral hemispheric cerebral blood flow on perfusion-weighted images (perfusion/diffusion mismatch), and (4) with total ICA occlusion on angiograms. We removed clots by aspiration and extraction with a microsnare through either a guiding or balloon guide catheter. Radiographic results, 7-day NIHSS, 3-month modified Rankin Scale, and procedure-related complications were evaluated. RESULTS: Of 10 patients treated with the balloon guide catheter to temporarily interrupt proximal flow, 7 obtained complete or partial recanalization. The 4 patients treated with the guiding catheter had no recanalization. Of the 7 patients with recanalization, 6 had favorable 7-day neurologic and 3-month functional outcome; all showed anatomic crossflow via the anterior communicating artery. A procedure-related complication, distal embolization into the ipsilateral anterior cerebral artery, occurred in 1 patient. CONCLUSION: Balloon guide catheter-assisted clot removal therapy for embolic ICA occlusion may provide a high recanalization rate and good clinical outcome in patients with anatomic crossflow.

An integrated radiation hybrid map of bovine chromosome 18 that refines a critical region associated with multiple ocular defects in cattle.

Congenital multiple ocular defects (MOD) of Japanese black cattle is a hereditary ocular disorder with an autosomal recessive mode of inheritance showing developmental defects of the lens, retina and iris, persistent embryonic eye vascularization and microphthalmia. The MOD locus has been mapped by linkage analysis to a 6.6-cM interval on the proximal end of bovine chromosome 18, which corresponds to human chromosome 16q and mouse chromosome 8. To refine the MOD region in cattle, we constructed an integrated radiation hybrid (RH) map of the proximal region of bovine chromosome 18, which consisted of 17 genes and 10 microsatellite markers, using the SUNbRH7000 panel. Strong conservation of gene order was found among the corresponding chromosomal regions in cattle, human and mouse. The MOD-critical region was fine mapped to a 59.5-cR region that corresponds to a 6.3-Mb segment of human chromosome 16 and a 4.8-Mb segment of mouse chromosome 8. Several positional candidate genes, including FOXC2 and USP10, were identified in this region.

A nucleotide substitution responsible for the tawny coat color mutation carried by the MSKR inbred strain of mice.

"Tawny" is an autosomal recessive coat color mutation found in a wild population of Mus musculus molossinus. The inbred strain MSKR carries the mutation. The causative gene Mc1r(taw) of the tawny phenotype is the second recessive allele at the melanocortin 1 receptor locus and is dominant to the first recessive allele, "recessive yellow" (Mc1r(e)). The Mc1r(taw) gene has six nucleotide substitutions, and its forecasted transcript has three amino acid substitutions (i.e., V101A, V216A, W252C). Though the nucleotide substitutions leading to V101A and V216A exist in various mouse strains, the nucleotide substitution leading to W252C exists in only tawny-colored mice. Thus this substitution is considered to be responsible for the expression of the tawny coat color. The frequency of the allele having this nucleotide substitution was 9.21% in the wild M. m. molossinus population inhabiting Sakai City, Osaka Prefecture, Japan, where the ancestral mice of the MSKR strain were captured.

The Dentin matrix protein 1 (Dmp1) is specifically expressed in mineralized, but not soft, tissues during development.

Dentin Matrix Protein 1 (Dmp1) was originally identified from dentin. However, its expression and function in vivo are not clear. To clarify these two issues, we have generated mice carrying a truncated Dmp1 gene by using gene targeting to replace exon 6 with a lacZ gene. Northern blot analysis shows the expected 5.8-kb Dmp1-lacZ fusion transcript and loss of the wild-type 2.8-kb Dmp1 transcript, confirmed by a lack of immunostaining for the protein. Using heterozygous animals, we demonstrate that Dmp1 is specific for mineralized tissues. Not previously shown, Dmp1 is also expressed in pulp cells. Dmp1-deficient embryos and newborns display no apparent gross abnormal phenotype, although there are a modest expansion of the hypertrophic chondrocyte zone and a modest increase in the long bone diameter. This suggests that DMP1 is not essential for early mouse skeletal or dental development.

Renal reabsorption of magnesium and calcium by cattle with renal tubular dysplasia.

The concentrations of magnesium and calcium in the serum and urine and their rates of clearance were determined in cattle with renal tubular dysplasia, an autosomal recessive hereditary disease associated with a deletion of the paracellin-1 gene in Japanese Black cattle. There were no significant differences in the serum or urine magnesium concentrations between normal cattle and cattle which were heterozygous or homozygous for the condition. Serum calcium concentrations tended to be lower in the homozygous cattle, and the serum creatinine and urea nitrogen concentrations were significantly higher in the homozygous cattle. The ratio of magnesium:creatinine and the fractional excretion of magnesium were higher in cattle with the disease than in normal cattle. There were no significant differences in urine calcium concentration, the calcium:creatinine ratio, and fractional excretion of calcium between normal cattle and cattle which were homozygous or heterozygous for the condition. The creatinine clearance was significantly lower in the homozygous cattle than in normal cattle. The clearance, excretion rate, reabsorption rate and reabsorption rate:clearance ratio of magnesium in cattle with renal tubular dysplasia were significantly lower than in normal cattle. The clearance rate and reabsorption rate of calcium were also significantly lower in the affected cattle, but the excretion rate and reabsorption rate:clearance of calcium were not different between the normal cattle and the cattle homozygous for the condition. In cattle with the condition the rate of reabsorption of magnesium by the kidneys was low, but the rate of reabsorption of calcium was normal.

The bovine fibroblast growth factor receptor 3 (FGFR3) gene is not the locus responsible for bovine chondrodysplastic dwarfism in Japanese brown cattle.

Fibroblast growth factor receptor 3 (FGFR3) is one of the four distinct membrane-spanning tyrosine kinase receptors for fibroblast growth factors. The FGFR3 is a negative regulator of endochondral ossification and mutations in the FGFR3 gene have been found in patients of human hereditary diseases with chondrodysplastic phenotypes. Recently, we mapped the locus responsible for hereditary chondrodysplastic dwarfism in Japanese brown cattle to the distal region of bovine chromosome 6 close to the FGFR3 gene, suggesting that FGFR3 was a positional candidate gene for this disorder. In the present study, we isolated complementary DNA (cDNA) clones containing the entire coding region of the bovine FGFR3 gene. Comparison of the nucleotide sequence between affected and normal animals revealed no disease-specific differences in the deduced amino acid sequences. We further refined the localization of FGFR3 by radiation hybrid mapping, which is distinct from that of the disease locus. Therefore we conclude that bovine chondrodysplastic dwarfism in Japanese brown cattle is not caused by mutation in the FGFR3 gene.

Hemosuccus pancreaticus: diagnosis with CT and MRI and treatment with transcatheter embolization.

We report the case of a 56-year-old woman with a presyncopal episode followed by melena. A sentinel clot sign in the pancreatic duct on precontrast computed tomography and the presence of a splenic artery aneurysm on postcontrast computed tomography strongly suggested a fistula between the aneurysm and the duct, as visualized by magnetic resonance imaging. The patient was treated successfully by complete embolization of the splenic artery aneurysm.