First norovirus outbreaks associated with consumption of green seaweed (Enteromorpha spp.) in South Korea.

In February 2012, an outbreak of gastroenteritis was reported in school A; a successive outbreak was reported at school B. A retrospective cohort study conducted in school A showed that seasoned green seaweed with radishes (relative risk 7·9, 95% confidence interval 1·1-56·2) was significantly associated with illness. Similarly, a case-control study of students at school B showed that cases were 5·1 (95% confidence interval 1·1-24·8) times more likely to have eaten seasoned green seaweed with pears. Multiple norovirus genotypes were detected in samples from students in schools A and B. Norovirus GII.6 isolated from schools A and B were phylogenetically indistinguishable. Green seaweed was supplied by company X, and norovirus GII.4 was isolated from samples of green seaweed. Green seaweed was assumed to be linked to these outbreaks. To our knowledge, this is the first reported norovirus outbreak associated with green seaweed.

Identification of oxidized serum albumin in the cerebrospinal fluid of ischaemic stroke patients.

BACKGROUND AND PURPOSE: Extensive evidence has shown that oxidative stress mediates neuronal death in animal models of hypoxic-ischaemia. Brain biomarkers of oxidative stress need to be identified in order to better understand and treat brain damage in human stroke patients. The present study was conducted to identify potential target proteins of oxidative stress in the cerebrospinal fluid (CSF) of stroke patients with acute ischaemic brain injury. METHODS: We performed two-dimensional polyacrylamide gel electrophoresis to separate protein samples obtained from the CSF of control and stroke patients. To determine protein oxidation levels, oxyblot was then used to detect protein carbonyls that were determined by formation of a stable 2,4-dinitrophenylhydrazine (DNP) product using an anti-DNP antibody. RESULTS: We found that oxidation of serum albumin was increased in the CSF from stroke patients as well as rats who underwent permanent middle cerebral artery occlusion (6.5%, 23%, respectively). In stroke patients, oxidized albumin levels correlated to neurologic indications. CONCLUSIONS: The present study suggests that oxidized albumin in CSF can be utilized as an oxidative stress marker in human stroke patients.

Intrathecal transplantation of human neural stem cells overexpressing VEGF provide behavioral improvement, disease onset delay and survival extension in transgenic ALS mice.

Amyotrophic lateral sclerosis (ALS) is the most common adult onset motoneuron disease. The etiology and precise pathogenic mechanisms of the disease remain unknown, and there is no effective treatment. Vascular endothelial growth factor (VEGF) has recently been shown to exert direct neurotrophic and neuroprotective effects in animal models of ALS. Here we show that intrathecal transplantation of immortalized human neural stem cells (NSCs) overexpressing human VEGF gene (HB1.F3.VEGF) significantly delayed disease onset and prolonged the survival of the SOD1G93A mouse model of ALS. At 4 weeks, post-transplantation grafted cells were found within the gray matter of the spinal cord. Furthermore, transplanted F3.VEGF cells that express neuronal phenotype (MAP2+) were found in the anterior horn of the spinal cord gray matter indicating that the transplanted human NSCs migrated into the gray matter, took the correct structural position, integrated into the spinal cord anterior horn and differentiated into motoneurons. Intrathecal transplantation of F3.VEGF cells provides a neuroprotective effect in the diseased spinal cord by concomitant downregulation of proapoptotic proteins and upregulation of antiapoptotic proteins. Our results suggest that this treatment modality of intrathecal transplantation of human NSCs genetically modified to overexpress neurotrophic factor(s) might be of value in the treatment of ALS patients without significant adverse effects.

Vertebral artery dominance contributes to basilar artery curvature and peri-vertebrobasilar junctional infarcts.

OBJECTIVES: The diameters of the vertebral arteries (VAs) are very often unequal. Therefore, this study investigated if unequal VA flow contributes to the development of basilar artery (BA) curvature and if it is a link to the laterality of pontine or cerebellar infarcts occurring around the vertebrobasilar junction. METHODS: Radiological factors were analysed (infarct laterality, VA dominance, BA curvature and their directional relationships) in 91 patients with acute unilateral pontine or posterior inferior cerebellar artery (PICA) territory infarcts. The "dominant" VA side was defined as either that the VA was larger in diameter or the VA was connected with the BA in more of a straight line, if both VAs looked similar in diameter on CT angiography. Multiple regression analysis was performed to predict moderate to severe BA curvature. RESULTS: The dominant VA was more frequent on the left side (p<0.01). Most patients had an opposite directional relationship between the dominant VA and BA curvature (p<0.01). Pontine infarcts were opposite to the side of BA curvature (p<0.01) and PICA infarcts were on the same side as the non-dominant VA side (p<0.01). The difference in VA diameters was the single independent predictor for moderate to severe BA curvature (OR per 1 mm, 2.70; 95% CI 1.22 to 5.98). CONCLUSIONS: Unequal VA flow is an important haemodynamic contributor of BA curvature and development of peri-vertebrobasilar junctional infarcts.

Impact of posterior communicating artery on basilar artery steno-occlusive disease.

BACKGROUND: Acute brainstem infarction with basilar artery (BA) occlusive disease is the most fatal type of all ischaemic strokes. This report investigates the prognostic impact of the posterior communicating artery (PcoA) and whether its anatomy is a safeguard or not. METHODS: Consecutive patients who had acute brainstem infarction with at least 50% stenosis of BA upon CT angiography (CTA) were studied. The configuration of PcoA was divided into two groups upon CTA: "textbook" group (invisible PcoA with good P1 and P2 segment) and "fetal-variant of PcoA" group (only visible PcoA with absent P1 segment). Baseline demographics, radiological findings and stroke mechanisms were analysed. A multiple regression analysis was performed to predict clinical outcome at 30 days (modified Rankin disability Scale (mRS

Comparison of the Incidence of parenchymal hematoma and poor outcome in patients with carotid terminus occlusion treated with intra-arterial urokinase alone or with combined IV rtPA and intra-arterial urokinase.

BACKGROUND AND PURPOSE: Patients with acute CTO generally have a poor prognosis, despite IV or IA thrombolytic treatment. The goal of this study was to analyze the results of patients with CTO who had IA urokinase treatment with or without initial IV rtPA based on a bridging protocol. MATERIALS AND METHODS: Sixteen consecutive patients with acute ischemic stroke due to CTO who had combined IV and IA or a single IA thrombolytic treatment were enrolled. The baseline characteristics and prognosis were described. The patients who did and did not develop a PH shortly after treatment were compared. RESULTS: The mean age was 66.4 years, and the median initial NIHSS score was 17. The median dose of IA urokinase was 320,000 U, and recanalization (TICI grade II-III) was achieved in 12 patients (75%). However, 5 patients died and 10 patients had poor prognosis with mRS 5-6 at discharge. Six patients (37.5%) with a PH had a higher NIHSS score 1 day after treatment (26.7 versus 13.6, P = .002), and they had more frequent mortality (66.7% versus 10.0%, P = .018) and worse prognosis (mRS 5-6; 100% versus 40%, P = .016) at discharge than patients without PH. CONCLUSIONS: Patients with CTO who received IA urokinase treatment based on a bridging protocol had a poor prognosis. The development of PH might affect this outcome.

Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy.

We evaluated the feasibility and safety of therapy with mesenchymal stem cells (MSCs) through consecutively intra-arterial and three repeated intravenous injections and compared the long-term prognosis between MSC-treated (n=11) and control multiple system atrophy (MSA) patients (n=18). The MSC-treated patients showed significantly greater improvement on the unified MSA rating scale (UMSARS) than the control patients at all visits throughout the 12-month study period. Orthostasis in UMSARS I items and cerebellar dysfunction-related items of UMSARS II items were significantly different in favor of MSC treatment compared to controls. Serial positron emission tomography scan in the MSC-treated group showed that increased fluorodeoxyglucose uptake from baseline was noted in cerebellum and frontal white matters. No serious adverse effects related to MSC therapy occurred. This study demonstrated that MSC therapy in patients with MSA was safe and delayed the progression of neurological deficits with achievement of functional improvement in the follow-up period.

The plasma alpha-synuclein levels in patients with Parkinson's disease and multiple system atrophy.

alpha-Synuclein, a synaptic protein of unknown function, is a major component of Lewy bodies and may play a role in the pathophysiological process of Parkinson's disease (PD). In this study, we measured the plasma alpha-synuclein levels in 105 patients with PD, 38 patients with multiple system atrophy (MSA), and 51 age-matched controls. The alpha-synuclein level was significantly elevated in patients with PD (79.9 +/- 4.0 pg/ml, p < 0.001) and in those with MSA (78.1 +/- 3.5 pg/ml, p = 0.019) compared with the level in controls (76.1 +/- 3.9 pg/ml). The alpha-synuclein level was higher in patients with PD than in those with MSA (79.9 +/- 4.0 vs 78.1 +/- 3.5, p = 0.016). Our study demonstrated that the alpha-synuclein level in plasma is elevated in patients with PD and MSA.

Pathogenesis of deep white matter medullary infarcts: a diffusion weighted magnetic resonance imaging study.

BACKGROUND AND PURPOSE: The pathogenesis of deep white matter medullary (WMM) artery infarcts remains controversial. To address this question, we analysed the stroke patterns of WMM infarcts using diffusion weighted magnetic resonance imaging (DWI) to detect embolic signals and investigate stroke subtypes according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classifications. METHODS: We identified WMM infarcts on DWI using templates to determine the subcortical vascular territories. We classified WMM infarcts into those with small artery disease (SAD), large artery disease (LAD), cardioembolism (CE), two or more aetiologies, or undetermined aetiology. Clinical course, risk factors, and cortical spotty lesions were compared. RESULTS: Of the 1420 consecutive patients, 103 (7.3%) met the criteria for WMM infarcts. The stroke subtypes were as follows: 65 (63.1%) patients with LAD, 18 (17.5%) with SAD, 12 (11.7%) with CE, four (3.9%) with two or more aetiologies, three (2.1%) with undetermined aetiology, and one (1.0%) with other determined aetiology. LAD (87.7%) or CE (83.3%) was significantly accompanied by cortical embolic signals as compared to SAD (0%, p<0.001). The LAD infarcts were larger and tended to be chain-like in shape. Ischaemic stroke recurrence was more common in strokes with cortical embolic signals than in those without embolic signals (18.9% v 0%, p = 0.009). CONCLUSIONS: In present study, the most common pathogenesis of WMM infarcts was LAD. Our study indicates that WMM infarcts accompanying cortical embolic signals warrant evaluation of the underlying embolic sources in the large artery or the heart.

Inflammatory markers, rather than conventional risk factors, are different between carotid and MCA atherosclerosis.

BACKGROUND: The apparent differences in risk factors for intra- and extracranial atherosclerosis are unclear and the mechanisms that underlie strokes in patients with intracranial atherosclerosis are not well known. We investigated the conventional vascular risk factors as well as other factors in stroke patients with large artery atherosclerosis. METHODS: Using diffusion weighted imaging (DWI) and vascular and cardiologic studies, we selected patients with acute non-cardioembolic cerebral infarcts within the middle cerebral artery (MCA) territory. Patients were divided into two groups: those with atherosclerotic lesions on the carotid sinus (n = 112) and those with isolated lesions on the proximal MCA (n = 160). Clinical features, risk factors, and DWI patterns were compared between groups. RESULTS: There were no differences in conventional risk factors, but markers for inflammation were significantly higher in patients with carotid atherosclerosis than in those with isolated MCA atherosclerosis (p < 0.01 for both). After adjustments for age/sex and the severity of stroke, an inverse correlation was observed between C-reactive protein levels and MCA atherosclerosis (odds ratio 0.57 per 1 mg/dl increase; 95% confidence interval 0.35 to 0.92; p = 0.02). Internal borderzone infarcts suggestive of haemodynamic causes were the most frequent DWI pattern in patients with MCA occlusion, whereas territorial infarcts suggesting plaque ruptures were most common in those with carotid occlusion. CONCLUSIONS: Our results indicate that inflammatory markers, rather than conventional risk factors, reveal clinical and radiological differences between patients with carotid and MCA atherosclerosis. Plaques associated with MCA atherosclerosis may be more stable than those associated with carotid atherosclerosis.

Association of the metabolic syndrome with intracranial atherosclerotic stroke.

To investigate the impact of metabolic syndrome (MetSD) on the development of intracranial atherosclerotic stroke, the authors evaluated the components of the MetSD in 512 patients with stroke. The MetSD was observed most frequently in patients with intracranial atherosclerosis (p = 0.007). In multiple regression analysis, the MetSD, but not conventional risk factors, was independently associated with intracranial atherosclerosis (p = 0.005). The results suggest that treatment of metabolic abnormalities may be an important prevention strategy for intracranial atherosclerosis.

Isolated middle cerebral artery disease: clinical and neuroradiological features depending on the pathogenesis.

BACKGROUND: Isolated atherosclerotic middle cerebral artery (MCA) disease is often difficult to differentiate from cardioembolic disease if intracranial atherosclerosis coexists with cardiac disease. OBJECTIVES: To evaluate whether clinical and neuroradiological features of isolated MCA disease differ according to the underlying aetiology. METHODS: Isolated MCA disease was defined as a unilateral angiographically occlusive lesion of the MCA on the symptomatic side without lesions of other intracranial or extracranial vessels. Patients with isolated MCA disease were divided into atherosclerotic and potentially cardioembolic, and the clinical, laboratory, and neuroradiological data analysed. RESULTS: Among the 850 consecutive patients with acute ischaemic stroke or transient ischaemic attack, 107 (12.6%) met the criteria for isolated MCA disease (76 with atherosclerotic disease and 31 with a potential source of cardiac embolism). Total anterior circulation infarcts were more common and baseline NIHSS score was higher in potentially embolic occlusions than in atherosclerotic disease (each p<0.001). While cortical infarcts and territorial infarcts were more common in the potential embolism group (p = 0.028 and p<0.001, respectively), subcortical border zone infarcts were more common in the atherosclerotic group (p<0.001). Multiple regression analysis showed that border zone infarcts and mild stroke were independently associated with atherosclerotic MCA disease, while territorial and cortical infarcts were associated with potential cardiac embolic disease. CONCLUSIONS: Clinical and neuroradiological characteristics can differentiate isolated atherosclerotic MCA disease from MCA disease associated with potential sources of cardiac embolism, and may reflect the differences in underlying pathogenesis.

Infarct patterns in atherosclerotic middle cerebral artery versus internal carotid artery disease.

OBJECTIVE: To compare clinical and radiologic characteristics of atherosclerotic middle cerebral artery (MCA) vs internal carotid artery (ICA) disease. METHODS: The authors defined atherosclerotic MCA and ICA disease as >50% symptomatic stenosis or occlusion without significant ICA and MCA stenosis on MR angiography. Patients with potential cardiac sources of embolism were excluded. The authors analyzed clinical, laboratory, and neuroradiologic data of the two groups. RESULTS: Among the 920 consecutive patients with acute ischemic strokes, 112 met the criteria for atherosclerotic MCA and 71 met the criteria for ICA disease. Clinically, the MCA group more frequently presented with lacunar syndrome (p = 0.001), whereas the ICA group more often presented with total anterior circulation infarct and had higher initial NIH Stroke Scale scores than the MCA group (all p < 0.001). Whereas deep perforator and internal border-zone infarcts were associated with MCA disease (p < 0.001 and 0.012), territorial infarcts and superficial perforator infarcts were associated with ICA disease (p < 0.001 and p = 0.009). The topographic patterns with respect to the degree of stenosis were also significantly different between the two groups. CONCLUSIONS: The clinical and radiologic stroke patterns were distinctively different between atherosclerotic MCA and ICA disease, suggesting different underlying pathogeneses.

An immunohistochemical analysis of heat shock protein 70, p53, and estrogen receptor status in carcinoma of the uterine cervix.

OBJECTIVES: It has been shown that heat shock proteins (HSPs) protect cells from death caused by various noxious stimuli. Overexpression of HSP70 seems to be related to hormonal regulation of cell proliferation and/or down-regulation of sex steroid receptors. Wild-type p53 has been reported to repress HSP70 gene expression. It has been shown that mutant p53-HSP70 complex is highly expressed in cancer. However, the relationship between HSPs and steroid receptors or tumor suppressor gene products has not been well understood in uterine cervical carcinoma. This study was undertaken to examine the expression of HSP70, estrogen receptor (ER), and p53 in carcinoma of the uterine cervix. In addition, we analyzed HPV infection status and compared it to such immunohistochemical parameters. We also analyzed the relationship between these biological products and their clinicopathologic characteristics. METHODS: Paraffin-embedded tissue sections were obtained from 84 patients with carcinoma of the uterine cervix. Expression of HSP70, p53, and ER was evaluated by immunohistochemical staining using anti-HSP70 monoclonal antibody (SPA810), anti-p53 (BP53.12), and ER1D5 antibody, respectively. PCR HPV detection was done by dot hybridization method. RESULTS: Positive staining of HSP70 was detected in 73% of the cases. HSP70 positivity was significantly higher in stage I cervical cancer than in stages II-IV (P = 0.02). This was associated with neither tumor size, lymph node status, parametrial involvement status, nor tumor markers (TA-4). Furthermore, there was no significant correlation between HSP70 positivity and the expression of p53 or ER or HPV infection status. CONCLUSION: These data suggested that HSP70 positivity was frequent in uterine cervical cancer, especially in the early stages. However, this was not significantly correlated with clinicopathologic characteristics nor with the expression of p53 or ER nor with HPV infection in carcinoma of the uterine cervix.