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Background: Antiphospholipid antibodies (aPLs) are associated with vascular occlusive events. Lupus anticoagulant (LA) and anticardiolipin antibody (aCL) are two aPLs commonly used for screening test. However, other aPLs are reported to play a role in the thrombotic events in other disorders, especially autoimmune disease. We investigated the clinical significance of the anti-annexin V antibody (aAV) in patients with acute cerebral ischemia; annexin V promotes anticoagulant activity via inhibition of prothrombin activation., Methods: A total of 187 patients with acute cerebral infarction or transient ischemic attack, and 66 control subjects were included in this prospective study. IgG type aAV was determined by enzyme-linked immunosorbent sandwich assay in the patient and control groups. The presence of LA and aCL were determined in the patient group using the usual screening method., Results: IgG aAV was detected in 26 of the 187 patients (13.9%), but only in three of the 66 control subjects (4.5%; P=0.043). Among the 26 aAV positive patients, only five patients were positive for LA or aCL. The presence of IgG aAV was significantly associated with acute cerebral ischemia: one stroke event (OR, 4.39; 95% CI, 1.21-16.01), and two or more stroke events (OR, 3.91; 95% CI, 1.09-14.07)., Conclusion: IgG aAV was detected in a significant percentage of the patients with acute cerebral ischemia compared with the control group. The presence of IgG aAV did not usually coincide with LA or aCL. Thus aAV should be considered as a possible associated factor for acute cerebral ischemia., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Purpose: We assessed the prognostic value of metabolic tumor volume (MTV) measured using(18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) inpatients with locally advanced head and neck squamous cell carcinoma (HNSCC)., Methods: We retrospectively reviewed 56 patients (51 men, five women; mean age 56.0 ± 8.8years) who had locally advanced HNSCC and underwent FDG PET/CT for initial evaluation. All patients had surgical resection and radiotherapy with or without concurrent chemotherapy. The peak standardized uptake value (SUVpeak) and MTV of the target lesion, including primary HNSCC andmetastatic cervical lymph nodes, were measured from FDG PET/CT images. We compared SUVpeak, MTV, and clinicopathologic variables such as age, Eastern Cooperative Oncology Group (ECOG) performance status, pN stage, pT stage, TNM stage, histologic grade and treatment modality to disease-free survival (DFS) and overall survival (OS)., Results: On the initial FDG PET/CT scans, the median SUVpeak was 7.8 (range, 1.8-19.0) and MTV was17.0 cm(3) (range, 0.1-131.0 cm(3)). The estimated 2-year DFS and OS rates were 67.2% and 81.8%. The cutoff points of SUVpeak 6.2 and MTV 20.7 cm(3) were the best discriminative values for predicting clinical outcome. MTV and ECOG performance status were significantly related to DFS and OS on univariate and multivariate analyses (p < 0.05)., Conclusion: The MTV obtained from initial FDG PET/CT scan is a significant prognostic factor for disease recurrence and mortality in locally advanced HNSCC treated with surgery and radiotherapy with or without chemotherapy.

Eosinophilic vasculitis has been described as part of Churg-Strauss syndrome (CSS), but it also affects the central nervous system in <10% of cases. However, spinal cord involvement in CSS has not been reported. We report a patient with myelopathic symptoms, with a two-year history of asthma. Laboratory tests revealed leukocytosis, with 31.7% eosinophils. A chest computed tomographic scan and radiography showed patchy bilateral areas of consolidation, predominantly involving the peripheral regions of the lower lobes. Spinal cord magnetic resonance imaging (MRI) revealed high-signal-intensity lesions at the C3-C5 and T1-T4 spinal levels on T2-weighted images. A microscopic evaluation revealed an eosinophil-rich inflammatory infiltrate with fibroid necrosis of a vessel wall, and granuloma formation in the small veins was not clearly visible. To the best of our knowledge, this is the first case of eosinophilic vasculitis of the spinal cord associated with CSS, and the patient responded well to steroids., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Convection enhanced delivery of 6-hydroxydopamine (6-OHDA) to the rat striatum results in a model of Parkinson's disease. An important feature of this unilateral model is the progressive loss of dopaminergic (DA) neurons over the course of several weeks. To improve the understanding of this model, gene expression changes in the substantia nigra, which contains the DA neuron cell bodies, and the striatum, which contains the DA neuron synaptic terminals, were examined using DNA microarrays. Samples were collected and behavior was analyzed from vehicle and toxin treated animals at 3 days, 1 week, 2 weeks and 4 weeks following 6-OHDA treatment. Tissue DA content was determined and samples from animals which exhibited a substantial depletion of striatal DA were included in the subsequent gene expression analysis. The results of the gene expression analysis indicated that 6-OHDA elicits a vigorous inflammatory response, comprised of several distinct pathways, in the striatum at the earliest time point tested. In contrast, relatively few gene expression changes were observed in the SN at the 3-day time point. In both tissues examined there was evidence for a vigorous inflammatory response at the 1- and 2-week time points, which was substantially diminished by the 4-week time point. Inflammation plays a prominent role in the 6-OHDA model of Parkinson's disease.

All-trans retinoic acid (ATRA) affects on the function of antigen presenting cells with somewhat controversies. We investigated the effects of ATRA on differentiation, maturation and function of human monocyte-derived dendritic cells (DCs). Low dose (10(-14)M) or high dose (10(-6)M) of ATRA was added either when monocytes were differentiated into immature DCs (imDCs) or mature DCs (mDCs) were induced. Apoptotic cell populations were dramatically increased in imDCs or mDCs with increasing concentration of ATRA. The productions of IL-12p40 and IL-12p70 were significantly suppressed in imDCs or mDCs induced by the addition of ATRA in the dose-dependent manner, whereas IL-10 was increased. DCs cultured with ATRA induced the differentiation of naïve T cells towards a helper T cell type 2 (Th2) response and expansion of CD4(+)CD25(+)Foxp3(+) regulatory T cells. Allostimulatory capacity of DCs was suppressed with increasing concentration of ATRA. These findings suggest that ATRA inhibits the effects on the differentiation, maturation and function of human monocyte-derived DCs in vitro and also enhance the differentiation of naïve T cell toward the Th2 type., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Anion exchange of BF(4)(-) occurs by stirring a cobalt(III) complex of salen-type ligand tethered by four quaternary ammonium BF(4)(-) salts over a slurry of NaX in CH(2)Cl(2), affording a complex containing four X's per cobalt (X = 2,4,5-trichlorophenolate, 6; X = 4-nitrophenolate, 10; X = 2,4-dichlorophenolate, 12). The (1)H and (13)C NMR spectra are in agreement with an unusual imine uncoordinated structure. The two salen-phenoxys and the two X's persistently coordinate with cobalt(III) to form a square planar cobaltate complex while the other two X's scramble through coordination and decoordination to the axial sites of the square plane. Another form of the complex (X = 2,4,5-trichlorophenolate, 14; X = 4-nitrophenolate, 15; X = 2,4-dichlorophenolate, 16) is also prepared, in which the scrambling two X's in 6, 10, or 12 are replaced with the corresponding [X...H...X](-) homoconjugate. These complexes, which adopt an unusual imine uncoordinated structure, are excellent catalysts for CO(2)/propylene oxide copolymerization (turnover frequency (TOF), 8300-16,000 h(-1)). In all cases, the complex containing the homoconjugate [X...H...X](-) shows higher activity than the corresponding phenol-free complex. Among the prepared complexes, 4-nitrophenol-4-nitrophenolate homoconjugate complex 15 showed the best performance (TOF, 16,000 h(-1); selectivity, 98%; M(n), 273,000), allowing for replacement of the explosive 2,4-dinitrophenolate complex.

Salen-type ligands comprised of ethylenediamine or 1,2-cyclohexenediamine, along with an salicylaldehyde bearing a methyl substituent on its 3-position and a -[CR(CH(2)CH(2)CH(2)N(+)Bu(3))(2)] (R = H or Me) on its 5-position, unexpectedly afford cobalt(III) complexes with uncoordinated imines. In these complexes, two salen-phenoxys and two 2,4-dinitrophenolates (DNPs), which counter the quaternary ammonium cations, coordinate persistently with cobalt, while two other DNPs are fluxional between a coordinated and an uncoordinated state in THF at room temperature. The complexes of this binding mode show excellent activities in carbon dioxide/propylene oxide copolymerization (TOF, 8300-13,000 h(-1)) but with some fluctuation in induction times (1-10 h), depending on how dry the system is. The induction time is shortened (<1.0 h) and activity is increased approximately 1.5 times upon the replacement of the two fluxional DNPs with 2,4-dinitrophenol-2,4-dinitrophenolate homoconjugation ([DNP...H...DNP](-)). Imposing steric congestion either by replacing the methyl substituent on the salicylaldehyde with tert-butyl or by employing H(2)NCMe(2)CMe(2)NH(2) instead of ethylenediamine or 1,2-cyclohexenediamine results in conventional imine-coordinating complexes, which show lower activities than uncoordinated imine complexes.

We investigated to establish CD40-activated B cells (CD40-B cells) as alternative antigen-presenting cells (APCs) for the induction of myeloma-specific cytotoxic T lymphocytes (CTLs). To generate CD40-B cells, peripheral blood mononuclear cells were co-cultured with CD40L-transfected J558 cells in the presence of IL-4, insulin, transferrin, and cyclosporine for 14 days, and pulsed with myeloma lysates. The CD40-B cells consistently expressed high levels of CD80, CD86, CD54, CCR7, and HLA-DR. The CD40-B cells produced IL-12, IFN-gamma, and IL-6 during the culture period, but not IL-10. In addition, the CD40-B cells showed potent allogeneic T-cell stimulatory capacities that depended on the dose ratio and had the potential to polarize naïve T cells into Th1 subsets. The CD40-B cells loaded with tumor lysates induced strong target-specific CTLs, based on large numbers of IFN-gamma secreting cells and higher cytotoxic activity against target cells compared to the CD40-B cells without the tumor lysates. These results suggest that CD40-B cells loaded with myeloma lysates might provide alternative APCs for cellular immunotherapy in patients with myeloma.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy with bimodal onset age distribution. The age of onset is between 5-18 yr in juvenile DM and 45-64 yr in adult DM. DM has a distinct clinical manifestation characterized by proximal muscle weakness, skin rash, extramuscular manifestations (joint contracture, dysphagia, cardiac disturbances, pulmonary symptoms, subcutaneous calcifications), and associated disorders (connective tissue disease, systemic autoimmune diseases, malignancy). The pathogenesis of juvenile and adult DM is presumably similar but there are important differences in some of the clinical manifestations, associated disorders, and outcomes. In this study, we investigated the clinical characteristics and outcomes of 16 patients with juvenile DM and 48 with adult DM. This study recognizes distinctive characteristics of juvenile DM such as higher frequency of neck muscle involvement, subcutaneous calcifications, and better outcomes.

Intestinal obstruction is a common surgical emergency. Transmesenteric hernia is an unusual cause of bowel obstruction that may result in irreversible damage of the bowel and a fatal outcome. Once incarceration of the bowel occurs, strangulation and gangrene follow immediately. The mortality rate associated with this condition is about 15%, but in the presence of gangrene of the bowel, the mortality rate is more than 50%. An accurate preoperative diagnosis of a transmesenteric hernia is very difficult and rarely made. Therefore, in patients with small bowel obstruction, in the absence of a history of previous surgery to suggest adhesions or an external hernia, the possibility of a transmesenteric hernia must be considered. We describe a case with gangrene of a long segment of the small bowel caused by a transmesenteric hernia through a large defect of small bowel mesentery in a child.

We investigated whether dendritic cells (DCs) from multiple myeloma (MM) patients were affected by loading tumor antigens and whether the defective DC function associated with MM could be overcome by the neutralization of VEGF. MM-specific DCs were generated by loading tumor lysates from myeloma cells at diagnosis or relapsed/progressive state, respectively. DCs loaded with tumor lysates showed lower phenotypic maturation, less T cell stimulatory capacity, less cytotoxic T lymphocyte activities, and highly abnormal cytokine secretions of IL-6 and IL-12, compared to myeloma lysate-unloaded DCs. The levels of VEGF, phospho-STAT3 and phospho-ERK1/2 in DCs were significantly higher with loading myeloma lysates. After the neutralization of VEGF activity, the DC function, signal transduction and cytokine production returned to normal. The defective function of DC in patients with MM is significantly affected by loading tumor antigens, correlating with abnormal STAT3 and the NF-kappaB signaling pathway, and neutralization of VEGF can overcome this DC dysfunction through the elimination of abnormal signal transduction.

Pulmonary arteriovenous malformations (PAVMs) are thin-walled aneurysms caused by abnormal communication between the pulmonary arteries and veins. Migraine headaches are sometimes the presenting clinical manifestation of PAVMs. Although embolotherapy, using detachable balloons or stainless steel coils, is generally accepted as the best choice for the treatment of multiple PAVMs, the mode of intervention for solitary PAVMs remains a subject of debate. We present a 43-yr-old woman with a 10-yr history of chronic migraines and dyspnea on exertion. She was discovered to have a large solitary centrally located PAVM, placing her at high risk of complications if she were to undergo percutaneous transcatheter embolization. She underwent successful surgical resection of her right middle lobe without complications, resulting in subsequent symptomatic improvement.

The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has gained much attention due to its potent therapeutic effect for cancer and rheumatoid arthritis. In this study, we attempted to develop the injectable formulations which can stabilize TRAIL and thus show prolonged blood circulation in vivo. The positively charged TRAIL was mixed with hyaluronic acid (HA), resulting in the formation of nanocomplexes. The zeta-potentials of nanocomplexes and their mean diameters were significantly dependent on the feed ratio of HA to TRAIL. The increase in the feed ratio of HA reduced the particle size and decreased the value of the zeta-potential. The bioactivity of TRAIL in the complexes was comparable to that of native TRAIL, indicating that the complex formation did not affect the activity of TRAIL. Furthermore, the stability of TRAIL in the complexes was retained for 6 days, during which the bioactivity of native TRAIL disappeared. When native TRAIL was subcutaneously injected into the rats, its plasma concentration was not detectable after 12h. In contrast, for HA/TRAIL nanocomplexes in 1% HA solution, substantial amount of TRAIL was circulated in blood for up to 5 days. These results imply that HA-based formulations of TRAIL hold the potential as the therapeutics.

New basal insulin formulation was designed and their structural characteristics were investigated in vitro and biological activities in type 1 diabetic rats. Zinc-crystallized insulin was physically loaded into hydrophobically modified glycol chitosan (HGC) nanoparticles by a dialysis method. The series of insulin-HGC formulations were prepared with different feed weight ratio of insulin to HGC from 0.5:1 to 4:1. The loading contents of insulin and size distribution of insulin-HGCs were characterized, and blood glucose responses were investigated in streptozotocin-induced diabetic rats after single subcutaneous injection of regular insulin and insulin-HGCs. The highest loading efficiency and content were obtained in insulin-HGC when a 1:1 feed weight ratio of insulin to HGC was employed. The hydrodynamic diameter of insulin-HGC nanoparticles were in the range of 200 to 500 nm with narrow size distribution. Insulin-HGC effectively sustained insulin release up to 40% within 12 hours followed by a slower controlled release. Insulin-HGC showed an extended blood glucose lowering effect up to 24 h and provided normal blood glucose levels after oral glucose (1.5 g/kg) load at 24 hours post-injection while regular insulin showed severe hypoglycemia. The prolonged time action profiles and low variability of insulin-HGC formulation resulted in improved blood glucose control in diabetic rats and fulfilled a pattern desirable of a basal insulin.

Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis. Cerebellar involvement is rare in this syndrome. We report a 37-year-old woman with slowly progressive cerebellar ataxia, dysmetria of limbs, nystagmus, and dysarthria, bilateral painful axillary masses, and generalized arthralgia. Brain MRI revealed cerebellar atrophy with focal lesions in the pons, middle cerebellar peduncle, and the cerebellum. She underwent incisional biopsy of her axillary masses which showed findings consistent with ECD. An MRI of her lower extremities revealed lesions in the diaphyses, metaphyses, and epiphyses of the proximal tibia and distal femur bilaterally. This is a rare case of cerebral ECD with progressive cerebellar syndrome associated with cerebellar atrophy.

Congenital myopathies are clinical and genetic heterogeneous disorders characterized by skeletal muscle weakness and specific structural changes in muscle fiber. Congenital myopathy with fiber type disproportion (CFTD) is an established disorder of congenital myopathy. CFTD is characterized by non-progressive childhood neuromuscular disorders with a relatively good prognosis and type 1 fiber predominance and smallness. Congenital myopathy with type 1 fiber predominance (CMT1P) is also a distinct entity of congenital myopathy characterized by non-progressive childhood neuromuscular disorders and type 1 fiber predominance without smallness. Little is known about CMT1P. Clinical characteristics, including dysmorphic features such as hip dislocation, kyphoscoliosis, contracture, and high arch palate, were analyzed along with laboratory and muscle pathologies in six patients with CMT1P and three patients with CFTD. The clinical manifestations of CFTD and CMT1P were similar. However, the frequency of dysmorphic features is less in CMT1P than in CFTD. Long term observational studies of CMT1P are needed to determine if it will change to another form of congenital myopathy or if CMT1P is a distinct clinical entity.

Pneumomediastinum and subcutaneous emphysema generally occurs following trauma to the esophagus or lung. It also occurs spontaneously in such situations of elevating intra-thoracic pressure as asthma, excessive coughing or forceful straining. We report here on the rare case of a man who experienced the signs of pneumomediastinum and subcutaneous emphysema after a prolonged bout of intractable hiccup as the initial presenting symptoms of multiple sclerosis.

Acyclic o-phenylene-bridged bis(anilido-aldimine) compounds, o-C(6)H(4){C(6)H(2)R(2)N=CH-C(6)H(4)-(H)N(C(6)H(3)R'(2))}(2) and related 30-membered macrocyclic compounds, o-C(6)H(4){C(6)H(2)R'(2)N=CH-C(6)H(4)-(H)N-C(6)H(2)R(2)}(2) (o-C(6)H(4)) are prepared. Successive additions of Me(2)Zn and SO(2) gas to the bis(anilido-aldimine) compounds afford quantitatively dinuclear mu-methylsulfinato zinc complexes, o-C(6)H(4){(C(6)H(2)R(2)N=CH-C(6)H(4)-N(C(6)H(3)R'(2))-kappa(2)-N,N)Zn(mu-OS(O)Me)}(2) (R = iPr and R' = iPr, 29; R = Et and R' = Et, 30; R = Me and R'= Me, 31; R = Me and R' = iPr, 32; R = Et and R' = Me, 33; R = Et and R' = iPr, 34; R = iPr and R' = Et, 35) and o-C(6)H(4){C(6)H(2)R'(2)N=CH-C(6)H(4)-N-C(6)H(2)R(2)-kappa(2)-N,N)Zn(mu-OS(O)Me)}(2) (o-C(6)H(4)) (R = Et and R'= Et, 36; R = Me and R' = Me, 37; R = iPr and R' = Me, 38; R = Et and R' = Me, 39; R = Me and R'= iPr, 40). Molecular structures of 34 and 40 are confirmed by X-ray crystallography. Complexes 30-35 show high activity for cyclohexene oxide/CO(2) copolymerization at low [Zn]/[monomer] ratio (1:5600), whereas the complex of mononucleating beta-diketiminate {[(C(6)H(3)Et(2))N=C(Me)CH=C(Me)N(C(6)H(3)Et(2))]Zn(mu-OS(O)Et)}(2) shows negligible activity in the same condition. Activity is sensitive to the N-aryl ortho substituents and the highest activity is observed with 32. Turnover number up to 2980 and molecular weight (M(n)) up to 284 000 are attained with 32 at such a highly diluted condition as [Zn]/[monomer] = 1:17 400. Macrocyclic complexes 36-40 show negligible activity for copolymerization.

We report on a 32-year-old woman who developed reversible cortical blindness and right-sided weakness after cesarean section at 36 weeks of gestation, due to preeclampsia. An initial brain MRI demonstrated high signal intensity lesions in the bilateral occipito-parietal and left frontal lobes on T2-weighted and diffusion-weighted imaging. All of the lesions showed low signal intensity on apparent diffusion coefficient (ADC) map, which were compatible with cytotoxic edema, and MR angiography (MRA) showed diffuse vasospasm of the intracranial vessels. A follow-up brain MRI showed that most of the lesions disappeared and the vasospasm also resolved. This case suggests that the cytotoxic edema in preeclampsia may evolve differently from the pattern in cerebral infarction and explains the relatively benign course of the neurological signs in preeclampsia.

Limb-girdle muscular dystrophy type 2B (LGMD2B), a subtype of autosomal recessive limb-girdle muscular dystrophy (ARLGMD), is characterized by a relatively late onset and slow progressive course. LGMD2B is known to be caused by the loss of the dysferlin protein at sarcolemma in muscle fibers. In this study, the clinical and pathological characteristics of Korean LGMD2B patients were investigated. Seventeen patients with ARLGMD underwent muscle biopsy and the histochemical examination was performed. For the immunocytochemistry, a set of antibodies against dystrophin, alpha, beta, gamma, delta-sarcoglycans, dysferlin, caveolin-3, and beta-dystroglycan was used. Four patients (24%) showed selective loss of immunoreactivity against dysferlin at the sarcolemma on the muscle specimens. Therefore, they were classified into the LGMD2B category. The age at the onset of disease ranged from 9 yr to 33 yr, and none of the patients was wheelchair bound at the neurological examination. The serum creatine kinase (CK) was high in all the patients (4010-5310 IU/L). The pathologic examination showed mild to moderate dystrophic features. These are the first Korean LGMD2B cases with a dysferlin deficiency confirmed by immunocytochemistry. The clinical, pathological, and immunocytochemical findings of the patients with LGMD2B in this study were in accordance with those of other previous reports.

Centronuclear myopathy (CNM) is a rare congenital myopathy that is characterized by centrally placed nuclei in the muscle fibers. Based on the time of onset and the mode of inheritance, CNM can be divided into three distinct forms: the severe neonatal form, the childhood onset form, and the adult onset form. This paper describes the case of a female patient with CNM, in whom the disease manifested itself in the fifth decade of life, without any prior family history of such disorders. To the best of our knowledge, this is a rare case of late adult-onset CNM.

Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) is a rare but distinct form of nonprogressive, congenital myopathy. CMNDU1 is characterized by a type 1 muscle fiber content of more than 99%. This condition has only been previously described in a few reports. The authors report an 11-year-old girl who exhibited delayed developmental milestones, proximal muscle weakness, and bilateral ptosis. Her serum creatine kinase level was normal but an electromyographic study showed myopathic changes. A biopsy specimen from the left deltoid muscle revealed a uniformity of type 1 fibers (greater than 99%) with a moderate variation in fiber size. This is the first case of CNMDU1 reported in Korea.

Context: Prompt and precise measurement of neuronal damage in acute cerebral infarction is important to determine the prognosis of functional outcome. A feasible biochemical marker such as the neuron-specific enolase (NSE) level has been used to detect various diseases involving the central nervous system., Objective: To determine whether the initial serum NSE level is a useful marker for predicting the severity of clinical neurological deficits and the extent of neuronal damage in acute anterior-circulation infarction., Design: Case-control study with biochemical-clinicoradiological correlation., Setting: Tertiary care center., Participants: Eighty-one patients and 77 age- and sex-matched control subjects., Main Outcome Measures: Patients with anterior-circulation infarction underwent intravenous serum NSE sampling within 24 hours after symptom onset. Recent infarction was confirmed by T2-weighted and diffusion-weighted magnetic resonance imaging of the brain about 1 week after the onset of stroke. Volumetric analysis of infarction was also performed. The National Institutes of Health Stroke Scale score was measured on admission to the hospital and 1 week after symptom onset., Results: The patients' initial serum NSE levels were statistically significantly higher than the controls (P<.05). The initial serum NSE level highly correlated with the volume of infarction seen on T2-weighted magnetic resonance imaging of the brain (r = 0.62, P<.001) and with the National Institutes of Health Stroke Scale score obtained on hospital admission (r = 0.42, P =.002) and on the seventh day after the onset of stroke (r = 0.44, P<.001)., Conclusion: The initial serum NSE level is a reliable predictor for the extent of neuronal damage and the severity of clinical neurological deficits in acute anterior-circulation infarction.

The prediction of functional outcome in patients with acute cerebral infarction depends on many factors. Various techniques have been applied to predict severity and outcome after cerebral infarction. Neuron-specific enolase (NSE) is a component of a specific brain enzyme and a useful marker of brain injury. We evaluated the relation between initial serum NSE level and short- and long-term clinical outcome in 59 patients with acute cerebral infarction and in 38 age-matched healthy controls. Serum NSE levels were determined in patients with carotid artery (CA) territory cerebral infarction within 24 hours of onset. Brain MRI was performed four to seven days after stroke. Patients were divided into two groups: large CA territory infarction with a lesion extending cortex (cortex group), and small subcortical CA territory infarction (subcortical group) with a lesion confined to the subcortical white matter. We compared the initial serum NSE levels of the two groups. National Institute of Health Stroke Scale (NIHSS) was determined at admission and seven days after onset and the modified Rankin's scale was used at the 3 months follow-up after onset. Serum NSE levels were significantly elevated in patients with acute cerebral infarction compared with the normal controls (13.88 +/- 5.47 ng/dl vs. 8.15 +/- 1.53 ng/dl, p < 0.05). The initial (< 24 h) serum NSE level was higher in the cortical group than in the subcortical group (16.68 +/- 5.70 ng/dl vs. 10.98 +/- 3.34 ng/dl, p < 0.05). NIHSS on admission and on the 7th day correlated with the initial serum NSE level (p < 0.05), as were more severe functional outcomes, as determined 3 months after onset (p < 0.05). This study shows that initial serum NSE level may be a useful marker for severity in acute ischemic stroke, and that it may be well correlated with short-term and long-term functional outcomes.

Familial Alzheimer's disease (FAD) mutant forms of presenilin 1 (PS1) and 2 have been shown to sensitize cells to apoptotic cell death. Here we explore the effects of FAD mutant forms of PS1 on caspase activation during apoptosis. We show that caspase activation leads to increased generation of alternative C-terminal fragments (CTFs) from mutant as compared to wild-type (wt) PS1. For this purpose, very low expression levels of wt, A246E, L286V, and deltaE10 FAD mutant PS1 proteins in stably transfected human H4 neuroglioma cells were used to avoid artifactual induction of spontaneous apoptosis due to overexpression of PS1. Staurosporine treatment of these cells resulted in increased cell death and up to a 10-fold increase in caspase-3 activation in mutant versus wt PS1-expressing cell lines. Correspondingly, relative levels of caspase-cleaved PS1 CTFs were increased by five- to sixfold in the FAD mutant versus wt PS1 cells. Elevated caspase activation and caspase cleavage of FAD mutant PS1 suggest the possibility of either a direct proapoptotic effect of mutant PS1 or interference of mutant PS1 with antiapoptotic effects of wt PS1.