Blood-brain barrier dysfunction in Binswanger’s disease; an immunohistochemical study

Binswanger’s disease is pathologically characterized by a combination of diffuse cerebrovascular white matter lesions and lacunar infarcts in the basal ganglia and white matter. Although a blood-brain barrier (BBB) dysfunction has been implicated in the pathogenesis of these white matter (WM) lesions, few authors have addressed this problem. In the present study, we describe BBB dysfunction and its regional differences in the brains of Binswanger’s disease patients. Twelve brains from Binswanger’s disease patients (group III) were examined and compared with those from five patients with non-neurological disease (group I) and five cortical infarct patients without significant WM lesions (group II). Immunohistochemistry was performed for glial fibrillary acidic protein and vimentin as astroglial cell markers, and for immunoglobulins, complements and fibrinogen as extravasated serum protein markers. The grading scores for IgG extravasation were significantly higher in group III as compared to group I, in both the periventricular WM and the subcortical WM (P < 0.01). In group III, the scores in the periventricular WM and subcortical WM were significantly higher than in the subcortical U fibers and cerebral cortex (P < 0.01 for the periventricular WM; P < 0.001 for the subcortical WM), respectively. Clasmatodendritic astroglia, which had swollen cell bodies and large cytoplasmic vacuoles with disintegrated processes, incorporated the serum components IgG, IgM, C3d, C1q and fibrinogen, both in the periventricular WM and subcortical WM in 5 out of 12 (42%) Binswanger’s disease brains. These results indicate that WM lesions in Binswanger’s disease are accompanied by BBB dysfunction, although it remains uncertain whether BBB dysfunction is secondary to either chronic cerebral ischemia or arterial hypertension. Received: 25 April 1997 / Revised, accepted: 21 July 1997     

Scoliosis in cat cry syndrome

Background Cat cry syndrome is an autosomal disease accompanying abnormal deletion of chromosome 5 and occurs in only 1 of 50,000 neonates. Scoliosis has been reported as a skeletal complication in cat cry syndrome. The characteristics and causes of scoliosis in this rare syndrome are unknown. The purpose of this study was to present the characteristics of scoliosis in cat cry syndrome and to speculate on its causative mechanisms. Methods We report on 11 cases (5 boys and 6 girls) of cat cry syndrome. Detailed investigations of scoliosis, as well as physical and imaging examinations, were performed to characterize scoliosis and its causes. Average age at initial diagnosis of scoliosis was 4.3 years, and average age at final examination was 11.8 years. Results The incidence of scoliosis was as high as 73% (8/11). Most cases show a single right thoracic curve. Of the 8 patients with scoliosis, 3 patients who had increased muscular tone showed marked progression of scoliosis with growth. Conclusions Muscular hypertonia may play a key role in the progression of scoliosis in cat cry syndrome.     

Prediction of morbidity after lung resection with risk factors using treadmill exercise test.

OBJECTIVE: To predict accurate morbidity after lung resection using treadmill exercise test. METHODS: A total of 130 patients (108 men and 22 women, with mean age 67.1+/-11.4 years (range, 34-78 years)) of 1129 patients underwent standard lobectomy were performed both treadmill exercise test and spirometry preoperatively. We measured maximum oxygen uptake/body weight (VO2max/BW) and change in arterial blood oxygen pressure from rest to symptom-limited maximum loading (delta aPaO2) and calculated exercise-induced hypoxemia (delta PaO2/delta VO2/BW), and retrospectively compared these parameters for patients with and without complications. RESULTS: There were five patients with severe postoperative complications, including three requiring use of a respirator, two with home oxygen therapy. %Vital capacity, VC (%, 80.2+/-13.2 vs. 92.5+/-20.9, P=0.026), delta PaO2 (Torr, -29.3+/-4.3 vs. -13.2+/-10.8, P=0.0004), VO2max/BW (ml/min/kg, 16.5+/-2.9 vs. 20.6+/-5.1, P=0.018) and delta PaO2/delta VO2/BW (Torr/ml/min/kg, -1.98+/-0.26 vs. -0.57+/-0.47) were significantly associated with worse outcome. All the five patients with complications had delta PaO2/delta VO2/BW<-1.7. CONCLUSIONS: Treadmill exercise testing is a good method for assessment of cardiopulmonary reserve. Limited resection must be performed if delta PaO2/delta VO2/BW is under -1.7.     

Visual evoked potentials relating to imagery: Words for concrete objects versus absolute concepts

Summary We recorded visual evoked potentials (VEPs) elicited with high or low imaginable Chinese characters (HIC or LIC), representing concrete objects or absolute concepts, respectively. A closed circle (CC) acts as control stimulus. These were displayed (at 1.6° visual angle) for 35 ms on a TV monitor. Twenty-one channel VEPs (band-pas filter: 0.05–60 Hz), using balanced non-cephalic electrodes, were recorded from –100 to 924 ms for 11 right-handed male volunteers. The VEPs were analyzed by multivariate analysis of variance (MANOVA) and comparison of topographies at four remarkable peaks (P110, N160, P230 and N320). MANOVA showed significant differences (p< 0.001) for both conditions of channel and stimuli (HIC, LIC or CC). P100 for the CC-VEPs, N160 for the HIC-and LIC-VEPs, P230 for the CC-VEPs, and N320 for the HIC-VEPs were remarkable in the posterior scalp regions. Topographies at P100 and N160 showed no difference between the HIC-and LIC-stimuli. However, those at N320 showed difference between the HIC-and LIC-stimuli over the occipital and posterior temporal areas. Those results suggest that the responses at P100 and N160 might segregate Chinese characters from non Chinese characters. N320 suggested certain processes in imagery on recognizing Chinese characters over the occipital and posterior temporal areas.We are grateful to Dr. Yoshiji Kojima of Hamamatsu University for helpful comments.     

Papillo-Choledochectomy in the Operative Management of Mucosal Neoplasms of the Periampullary Region

Two patients with mucosal cancer of the periampullary region were treated with papillocholedochectomy, which entails removal of the papilla of Vater and the whole length of the common bile duct. The neoplasm is dissected out through the plane between the duodenal circular and longitudinal muscles, deep to the sphincter of Oddi and the fibromuscular layer of the bile duct. Pathological examination showed that cancer was confined to the mucosal layer without stromal invasion, and that the operation achieved radical cure. For mucosal cancer, papillo-choledochectomy is an alternative to pancreatoduodenectomy, provided that repeated frozen-section studies confirm the completeness of excision.     

FARP2 triggers signals for Sema3A-mediated axonal repulsion

Sema3A, a prototypical semaphorin, acts as a chemorepellent or a chemoattractant for axons by activating a receptor complex comprising neuropilin-1 as the ligand-binding subunit and plexin-A1 as the signal-transducing subunit. How the signals downstream of plexin-A1 are triggered upon Sema3A stimulation, however, is unknown. Here we show that, in the presence of neuropilin-1, the FERM domain-containing guanine nucleotide exchange factor (GEF) FARP2 associates directly with plexin-A1. Sema3A binding to neuropilin-1 induces the dissociation of FARP2 from plexin-A1, resulting in activation of FARP2's Rac GEF activity, Rnd1 recruitment to plexin-A1, and downregulation of R-Ras. Simultaneously, the FERM domain of FARP2 sequesters phosphatidylinositol phosphate kinase type I isoform PIPKIgamma661 from talin, thereby inhibiting its kinase activity. These activities are required for Sema3A-mediated repulsion of outgrowing axons and suppression of neuronal adhesion. We therefore conclude that FARP2 is a key molecule involved in the response of neuronal growth cones to class-3 semaphorins.     

Contribution of Asian mouse subspecies Mus musculus molossinus to genomic constitution of strain C57BL/6J, as defined by BAC-end sequence-SNP analysis

MSM/Ms is an inbred strain derived from the Japanese wild mouse, Mus musculus molossinus. It is believed that subspecies molossinus has contributed substantially to the genome constitution of common laboratory strains of mice, although the majority of their genome is derived from the west European M. m. domesticus. Information on the molossinus genome is thus essential not only for genetic studies involving molossinus but also for characterization of common laboratory strains. Here, we report the construction of an arrayed bacterial artificial chromosome (BAC) library from male MSM/Ms genomic DNA, covering approximately 1x genome equivalent. Both ends of 176,256 BAC clone inserts were sequenced, and 62,988 BAC-end sequence (BES) pairs were mapped onto the C57BL/6J genome (NCBI mouse Build 30), covering 2,228,164 kbp or 89% of the total genome. Taking advantage of the BES map data, we established a computer-based clone screening system. Comparison of the MSM/Ms and C57BL/6J sequences revealed 489,200 candidate single nucleotide polymorphisms (SNPs) in 51,137,941 bp sequenced. The overall nucleotide substitution rate was as high as 0.0096. The distribution of SNPs along the C57BL/6J genome was not uniform: The majority of the genome showed a high SNP rate, and only 5.2% of the genome showed an extremely low SNP rate (percentage identity = 0.9997); these sequences are likely derived from the molossinus genome.     

TRANSSYNAPTIC DEGENERATION IN THE INFERIOR OLIVARY NUCLEUS ASSOCIATED WITH PONTINE GLIOBLASTOMA

A case of glioblastoma arising in the pons of a 14-year-old boy in whom transsynaptic degeneration was found in the inferior olivary nucleus is reported. The tumor occupied most of the pons including the tegmental tract and invaded into the midbrain, medulla oblongata, cerebellar peduncles, thalamus, basal ganglia, and meninges. The right inferior olivary nucleus was devoid of the tumorous lesion, but many neurons were severely vacuolated. An im-munohistochemical study using glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and S-100 protein was performed. GFAP and S-100 protein were positive in the reactive glia of the nucleus and NSE gave a faint reaction in some degenerated neurons. These degenerative changes found in neurons of the inferior olivary nucleus were considered to be transsynaptic degeneration due to the destruction of the tegmental tract at the pons and of cerebellar peduncles by invasive pontine glioblastoma. ACTA PATHOL. JPN. 35: 1495–1500, 1985.     

Cytotoxicity evaluation of ceramic particles of different sizes and shapes

When artificial hip or knee joints are implanted in the human body, they release metallic, ceramic, and polymeric debris into the surrounding tissues. The toxicity of the released particles is of two types: chemical, caused by the released soluble ions and monomers, and mechanical, a result of mechanical stimulation produced by the insoluble particles. In this study, the cytotoxicity of particles of TiO2, Al2O3, ZrO2, Si3N4, and SiC for murine fibroblasts and macrophages were examined to evaluate just their mechanical toxicity because these particles are not expected to release soluble metal ions. Different sizes and shapes of TiO2 particles were used to evaluate the effect of size and shape on particle cytotoxicity. The results suggest that the cytotoxicity of ceramic particles does not depend on their chemical species. Cytotoxicity levels were lower than those of corresponding metal ions, indicating that the mechanical toxicity of particles is lower than the chemical toxicity of released soluble ions and monomers. The differences in size did not affect the mechanical toxicity of these particles. The dendritic particles had a higher cytotoxicity level for macrophages than did spindle and spheric particles.