Real-time detection and discrimination of visual perception using electrocorticographic signals.

OBJECTIVE: Several neuroimaging studies have demonstrated that the ventral temporal cortex contains specialized regions that process visual stimuli. This study investigated the spatial and temporal dynamics of electrocorticographic (ECoG) responses to different types and colors of visual stimulation that were presented to four human participants, and demonstrated a real-time decoder that detects and discriminates responses to untrained natural images. APPROACH: ECoG signals from the participants were recorded while they were shown colored and greyscale versions of seven types of visual stimuli (images of faces, objects, bodies, line drawings, digits, and kanji and hiragana characters), resulting in 14 classes for discrimination (experiment I). Additionally, a real-time system asynchronously classified ECoG responses to faces, kanji and black screens presented via a monitor (experiment II), or to natural scenes (i.e. the face of an experimenter, natural images of faces and kanji, and a mirror) (experiment III). Outcome measures in all experiments included the discrimination performance across types based on broadband γ activity. MAIN RESULTS: Experiment I demonstrated an offline classification accuracy of 72.9% when discriminating among the seven types (without color separation). Further discrimination of grey versus colored images reached an accuracy of 67.1%. Discriminating all colors and types (14 classes) yielded an accuracy of 52.1%. In experiment II and III, the real-time decoder correctly detected 73.7% responses to face, kanji and black computer stimuli and 74.8% responses to presented natural scenes. SIGNIFICANCE: Seven different types and their color information (either grey or color) could be detected and discriminated using broadband γ activity. Discrimination performance maximized for combined spatial-temporal information. The discrimination of stimulus color information provided the first ECoG-based evidence for color-related population-level cortical broadband γ responses in humans. Stimulus categories can be detected by their ECoG responses in real time within 500 ms with respect to stimulus onset.

Single trial detection of hand poses in human ECoG using CSP based feature extraction.

Decoding brain activity of corresponding highlevel tasks may lead to an independent and intuitively controlled Brain-Computer Interface (BCI). Most of today's BCI research focuses on analyzing the electroencephalogram (EEG) which provides only limited spatial and temporal resolution. Derived electrocorticographic (ECoG) signals allow the investigation of spatially highly focused task-related activation within the high-gamma frequency band, making the discrimination of individual finger movements or complex grasping tasks possible. Common spatial patterns (CSP) are commonly used for BCI systems and provide a powerful tool for feature optimization and dimensionality reduction. This work focused on the discrimination of (i) three complex hand movements, as well as (ii) hand movement and idle state. Two subjects S1 and S2 performed single `open', `peace' and `fist' hand poses in multiple trials. Signals in the high-gamma frequency range between 100 and 500 Hz were spatially filtered based on a CSP algorithm for (i) and (ii). Additionally, a manual feature selection approach was tested for (i). A multi-class linear discriminant analysis (LDA) showed for (i) an error rate of 13.89 % / 7.22 % and 18.42 % / 1.17 % for S1 and S2 using manually / CSP selected features, where for (ii) a two class LDA lead to a classification error of 13.39 % and 2.33 % for S1 and S2, respectively.

The apelin/APJ system induces maturation of the tumor vasculature and improves the efficiency of immune therapy.

Immature and unstable tumor vasculature provides an aberrant tumor microenvironment and leads to resistance of tumors to conventional therapy. Hence, normalization of tumor vessels has been reported to improve the effect of immuno-, chemo- and radiation therapy. However, the humoral factors, which can effectively induce maturation of tumor vasculature, have not been elucidated. In this study, we found that the novel peptide apelin and its receptor APJ can induce the morphological and functional maturation of blood vessels in tumors. This apelin-induced tumor vascular maturation enhances the efficacy of cancer dendritic cell-based immunotherapy and significantly suppresses tumor growth by promoting the infiltration of invariant natural killer T cells into the central region of the tumor and thereby robustly inducing apoptosis of tumor cells. Additionally, we showed APJ expression to be enhanced in the tumor endothelium in comparison with normal-state endothelial cells. These findings provide a new target for tumor vascular-specific maturation, which is expected to improve the efficacy of conventional cancer therapies.

Cytochrome P450 genetic polymorphisms influence the serum concentration of calcineurin inhibitors in allogeneic hematopoietic SCT recipients.

Calcineurin inhibitors are necessary as immunosuppressants during hematopoietic SCT (HSCT) to prevent alloreactivity, but have unfortunate toxicities. So, we investigated the association of gene polymorphisms with the initial calcineurin inhibitor concentration and the subsequent drug dose from day 1 to day 28 among patients who underwent HSCT at a single institution. We analyzed 58 serial cases of Japanese patients receiving GVHD prophylaxis with CsA (21 cases) or tacrolimus (37 cases). We investigated eight single-nucleotide polymorphisms: rs4244285 (CYP2C19), rs15524, rs4646450, rs3800959, rs776746 (CYP3A5), rs1128503, rs2032582 and rs1045642 (MDR1). The CsA concentration was significantly higher when the genotype of CYP3A5 rs15524 was T/T (P=0.044) or rs776746 was G/G (P=0.027). The CYP3A5 rs776746 and rs4646450 genotypes were also associated with tacrolimus concentration (P=0.013 and P=0.0058, respectively). The dosage of tacrolimus was remarkably reduced from day -1 to day 28 when the patient had the CYP3A5 rs4646450 C/C and/or rs776746 G/G genotype (P=0.0010 and P=0.0021, respectively). In this study, we show that genetic variation has a predictable effect on the pharmacological responses to calcineurin inhibitors in HSCT patients.

Detection of natural killer T cells in the sinus mucosa from asthmatics with chronic sinusitis.

BACKGROUND: Chronic sinusitis (CS) with asthma generally exhibits a high degree of sinus tissue eosinophilia and recurrence often occurs even after surgical therapy. However, the cause has not yet been fully clarified. AIMS OF THE STUDY: To elucidate the pathogenesis of this refractory disease, we examined the infiltration of natural killer T (NKT) and type 1 helper T (Th1)/type 2 helper T (Th2) cells, and the cytokine expression in the sinus mucosa. METHODS: Sinus mucosal specimens were obtained surgically from 16 CS patients with nasal polyps. The NKT cells, Th1/Th2 cells and the expression of IL-4, IL-5, IL-13 and IFN-gamma were examined by a polymerase chain reaction or flow cytometry. Nasal mucosal specimens from six other patients with allergic rhinitis (AR) were examined in a similar manner. RESULTS: The NKT cells were detected to varying degrees in the sinus mucosa from asthmatic CS patients, but neither in the nonasthmatics nor in the nasal mucosa from the patients with AR. The Th2 cells and Th2 cytokines were expressed at significantly higher levels in the sinus mucosa from the CS patients with asthma in comparison to those without asthma. However, the Th1 cell infiltration and IFN-gamma expression were not different between these groups. CONCLUSION: Natural killer T cells may, therefore, play important roles in the enhanced Th2 cytokine expression and increased infiltration of Th2 cells and eosinophils observed in the sinus mucosa from asthmatic CS patients through MHC-independent mechanisms.

Rathke's cleft cysts: differentiation from other cystic lesions in the pituitary fossa by use of single-shot fast spin-echo diffusion-weighted MR imaging.

OBJECTIVE: Rathke's cleft cysts are often difficult to differentiate from other sellar cystic lesions using conventional MR imaging. The purpose of this study was to investigate the usefulness of single-shot fast spin-echo (SSFSE) diffusion-weighted MR imaging (DWI) in the diagnosis of a Rathke's cleft cyst. PATIENTS AND METHODS: We examined retrospectively 29 patients with a histologically verified sellar or suprasellar lesion containing a fluid component; 12 patients had a Rathke's cleft cyst, 6 patients a craniopharyngioma, 5 patients a haemorrhagic pituitary adenoma, and 6 patients a cystic pituitary adenoma). Several regions of interest (ROIs) for apparent diffusion coefficient (ADC) measurements were identified in the fluid components of the lesions. For comparison, ADC values were normalized using a relative ADC (rADC), which was determined by dividing the ADC values of lesions by those of normal white matter and expressing the quotient as a ratio. RESULTS: SSFSE provides diffusion-weighted images without significant susceptibility artifacts. DWI-SSFSE revealed Rathke's cleft cysts as hypointense relative to the normal brain parenchyma in all cases. The mean value of ADC for Rathke's cleft cysts was 2.12 x 10(-3) mm(2)/sec. Both the ADC and relative ADC of the Rathke's cleft cysts were significantly increased compared to those of the cystic components of craniopharyngiomas and haemorrhagic components of pituitary adenomas in the subacute phase (P < 0.05). There was not a statistically significant difference between Rathke's cleft cysts and cystic components of pituitary adenomas (P < 0.05). CONCLUSIONS: DWI-SSFSE with ADC values provides objective information in the differential diagnosis of Rathke's cleft cysts from other sellar cystic lesions. In addition, DWI-SSFSE with ADC values is useful for differentiating Rathke's cleft cysts from craniopharyngiomas and haemorrhagic pituitary adenomas.

Usefulness of bone window CT images parallel to the transnasal surgical route for pituitary disorders.

OBJECTIVE: Before operating on 130 patients with pituitary disorders, we evaluated their bone window CT images sliced parallel to the transnasal surgical route to assess the surgical anatomy of the nasal cavity for transnasal surgery. METHODS: High resolution bone window CT was performed in 3- to 5-mm slices parallel to the imaginary line connecting the inferior margin of the piriform aperture and the top of the sellar floor, parallel to the transnasal surgical route. RESULTS: This CT angle was useful in evaluating the width and depth of the operative field, the bony components of the nasal conchas, deviation of the nasal septum, the bony structure and mucosa in the sphenoid sinus, and the condition of the sellar floor. In patients requiring repeat surgery, the location of thin or thick nasal mucosa, residual bony septum, and inadequate sellar floor opening were easily detected. CONCLUSIONS: Bone window CT images sliced parallel to the transnasal surgical route provide direct visualization of the nasal anatomy for the transnasal approach. This method is helpful in determining how far to remove the sellar floor laterally, especially in cases requiring repeat surgery.

Persistent primitive trigeminal artery imaged by three-dimensional computed tomography angiography--two case reports.

Three-dimensional computed tomography (3D CT) angiography was used to investigate two cases of persistent primitive arteries. 3D CT angiography and 3D CT demonstrated a persistent primitive trigeminal artery variant penetrating the lateral edge of the posterior clinoid process and running to the posterior medial side, and a persistent primitive trigeminal artery perforating the canal of the posterior clinoid process and the petrosal bone junction. 3D CT angiography can delineate these persistent primitive arteries and the anatomy relative to the bone structure simultaneously, so is very useful to identify the arterial line where the canal is penetrated.

Morphometric comparison of the human optic nerve fiber with various other human nerve fibers.

The morphometric characteristics of nerve fibers of the human optic nerve in the chiasmatic region were measured with the combination of an image analyzer and a computer, using the Luxol fast blue-periodic acid-Schiff-hematoxylin discriminative staining method. The mean axonal transverse area of the human optic nerve fibers was 0.644 +/- 0.361 micron 2. Comparison of the size of the axon of the human optic nerve fiber with that of various other human nerves showed optic nerve fibers were definitely thinner than the other nerve fibers, and were surrounded by a thinner myelin sheath. Optic nerves may be more liable to mechanical damage at surgery that previously believed.

[A resolving sign of acute subdural hematoma: from report of two cases].

A 7-year-old-boy (Case 1) and a 60-year-old-man (Case 2) presented with rare spontaneous resolution of acute subdural hematoma (ASDH). They were admitted with consciousness disturbance, drowsy in Case 1 and sleepy in Case 2. Initial CT showed ASDH associated with a low density band between the hematoma and the inner wall of the skull base, combined with right parietal contusion in Case 2. Repeat CT showed that the hematoma had resolved spontaneously after a few hours, and the patients regained clear consciousness next day in Case 1 within a few days in Case 2 without surgical treatment. The mechanism of spontaneous resolution of ASDH was thought to involve pulsatile flow of cerebrospinal fluid (CSF) through the tear in the arachnoid membrane, resulting in redistribution and dispersal of the hematoma, and retrograde flow into the subarachnoid space. The characteristic feature of the CT findings, the low density band between the hematoma and the inner wall of the skull bone, probably shows this process. Spontaneous resolution of ASDH requires that the brain compensatory function maintains the normal outflow of CSF, and controls the intracranial pressure by CSF buffering, blood outflow via the venous system, and brain elasticity. The low density band may be a useful finding to distinguish cases with good and bad prognosis.

[Large distal anterior cerebral artery aneurysm associated with azygos anterior cerebral artery: case report].

A 51-year-old woman presented with a distal anterior cerebral artery aneurysm (DACAA) manifesting as severe headache and monoparesis of the left lower limb. Computed tomography revealed subarachnoid hemorrhage in the interhemispheric fissure, bilateral sylvian fissures, and basal cistern, and a hematoma in the supracallosal region. Angiography showed a large aneurysm (23 x 18 mm) located on the distal end of the azygos anterior cerebral artery (azygos ACA) at the supracallosal portion. T2-weighted magnetic resonance imaging demonstrated the hematoma as a mixed intensity mass, compressing the corpus callosum downward, and the aneurysm as a flow void anterior to the hematoma. Unilateral frontoparietal parasagittal craniotomy was performed with a horse-shoe shaped incision. The aneurysm was clipped via the interhemispheric approach, and the hematoma was aspirated. Postoperative angiography showed disappearance of the aneurysm and intact azygos ACA. The patient was discharged with mild monoparesis, paresthesia of the left lower limb and diagnostic dyspraxia. DACAA almost always arises at or near the genu of the corpus callosum and is often associated with vascular anomaly. In the literature, 22 of 26 cases of large and giant DACAA were located at or near the genu, but only 3 cases, including ours, in the supracallosal area. 11 cases were associated with azygos ACA. Therefore, hemodynamic stress caused by vascular anomaly may be involved in the formation of large or giant DACAA in contrast with cases of normal DACAA.

Central nervous system metastases from Ewing's sarcoma--case report.

A 12-year-old boy presented with a rare case of intracranial metastasis 33 months after surgical treatment for Ewing's sarcoma of the rib. His chief complaints were headache, right hemiparesis, and disturbance of speech. Computed tomography revealed a large metastatic lesion in the left occipitoparietal region. The tumor was totally removed through an emergency operation. Seven months later the intracranial tumor recurred. Another operation was performed, but he showed spinal cord involvement at the T-10 level and died. The possibility of central nervous system metastasis should be considered in long-term follow-up survivors with Ewing's sarcoma.

[A case of chronic inflammatory demyelinating polyneuropathy with recurrent ophthalmoplegia, persistent conduction block, antibody activity against gangliosides GM1].

We report a 19-year-old female with chronic inflammatory demyelinating polyneuropathy (CIDP) with recurrent ophthalmoplegia. The patient had chronic, recurrent, asymmetrical, predominantly, distal limb weakness, and numbness of extremities with recurrent external ophthalmoplegia. Ophthalmoplegia developed in each attack of distal limb weakness, and also rapidly subsided with recovery of limb weakness. Motor nerve conduction studies revealed conduction block in more than one nerve and conduction velocities were generally normal in those segments of the nerve where conduction block was not detected. Serum anti-gangliosides GM1 IgM antibody investigated by ELISA was elevated. Thin-layer chromatography immunostaining also confirmed this result. Sural nerve biopsy showed normal findings. In spite of improvement of her signs and symptoms after prednisolone therapy, multifocal conduction block was persistent. Muscle power improved in association with decreased in anti-GM1 antibody activity. There were many reports of CIDP with cranial nerve involvements, but recurrent ophthalmoplegia in CIDP is rare. It is widely accepted that serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome. However, serum anti-GQ1b IgG antibody was not detected in this case. It is unclear whether anti-GM1 antibody may play a role to pathogenesis of ophthalmoplegia or not in this case.

Dissecting aneurysm in the proximal region of the posterior inferior cerebellar artery presenting as Wallenberg's syndrome--case report.

A 29-year-old female presented with an unusual case of Wallenberg's syndrome due to a dissecting aneurysm of the posterior inferior cerebellar artery (PICA) manifesting as a sensation of heaviness in the occipital region and vertigo. Magnetic resonance imaging revealed infarction of the lateral aspect of the medulla oblongata. Digital subtraction angiography (DSA) revealed a spindle-shaped dilatation of irregular contour in the proximal portion of the left PICA. Pooling of contrast medium was noted in the venous phase but not double lumen sign. A suboccipital craniectomy confirmed these findings macroscopically. Blood flow meter monitoring before and after proximal clipping of the diseased vessel ensured the safety of the procedure. Follow-up DSA 3 years after surgery revealed no evidence of aneurysm recurrence.

[Studies on kallikrein activity in diabetic patient with hypertension caused by nephropathy].

A radioimmunoassay was performed for direct measurement of urinary active and trypsin-activatable inactive kallikreins excretion in 34 patients with Type II diabetes mellitus. (1) Diabetics showed slightly low total (inactive plus active) kallikrein excretion, normal inactive kallikrein excretion and significantly low active kallikrein excretion and active-to-total kallikrein ratio. (2) Total kallikrein excretion was normal in normotensive diabetics and hypertensive diabetics without nephropathy, low in hypertensive diabetics with nephropathy. Active kallikrein excretion and active-to-total kallikrein ratio in hypertensive diabetics were remarkably low regardless of nephropathy. (3) Para amino hippurate clearance correlated with total kallikrein excretion in normal subjects and, with active kallikrein excretion and active-to-total kallikrein ratio in both normal subjects and diabetics, but not with total kallikrein excretion in diabetics. Creatinine clearance did not correlate with total, inactive kallikrein excretions and active-to-total kallikrein ratio. (4) A positive correlation was found between fractional sodium excretion and active kallikrein excretion in normal subjects, but not in diabetics. The results suggest that reduction in ratio of active-to-total kallikrein by renal dysfunction might decrease sodium excretion in diabetics with nephropathy.

Multiple forms of immunoreactive renin in human adrenocortical tumour tissue from patients with primary aldosteronism.

There is increasing evidence which suggests that the adrenal gland contains the renin-angiotensin cycle. The localization of renin has been reported to be mainly in the zona glomerulosa rather than the fasciculata medullary portion. In the present study we have investigated extracts from aldosteronomas (n = 3), which are believed to derive from the zona glomerulosa cells. In addition, we have attempted to characterize the biochemical properties of the adrenal renin. Sizable quantities of renin-like activity (32.0 +/- 7.7 ng of angiotensin I generated h-1 mg-1 of protein, mean +/- SEM) were detected in the extracts. This renin-like activity was inhibited by anti-renin antibody raised against pure renin (mean, 95% of the total renin-like activity), indicating that it was not due to the non-specific action of proteases such as cathepsin D. The optimum pH of the tissue renin-like enzyme was 6.0 for rat plasma substrate. Differences were found, however, in the molecular mass (36,000, 37,000, 44,000 and 48,000), binding to concanavalin A and isoelectric points (4.40, 4.68 and 5.00). These results confirm the existence of specific renin in aldosteronoma. Renin microheterogeneity could be evidence for local production of the enzyme.

Biochemical characterization of angiotensin-converting enzyme in human neuroblastoma tissue.

High activity of angiotensin-converting enzyme was demonstrated in human neuroblastoma tissue. This activity required the presence of chloride ion and was almost completely inhibited by a specific converting enzyme inhibitor captopril (10 nM), indicating that the activity measured is indeed angiotensin-converting enzyme. Furthermore, the biochemical features of the enzyme were closely similar to the well-known properties of human lung converting enzyme, such as molecular weight (290,000), optimum pH (8.0-8.5), the presence of glycoprotein residues, and dependence on chloride ion concentration. These results provide definitive evidence for the presence of true angiotensin-converting enzyme in human neuroblastoma tissue.

A hitherto unreported case of 21-hydroxylase deficiency associated with Bartter's syndrome and a balanced 6-9 translocation.

A description is given of a girl with the non-salt-losing type of congenital adrenal hyperplasia (CAH) and with Bartter's syndrome. In addition, the patient had a balanced translocation between 6q and 9p. Although the possibility cannot be ruled out fully that an excess of progesterone might modify the renin-aldosterone axis to some extent, the finding that dexamethasone therapy improved the clinical features of CAH but failed to correct metabolic disorders in electrolyte balance strongly suggests the coexistence of the two clinical entities. Chloride transport at the distal tubule was impaired moderately in the patient, which suggests that her defective reabsorption of chloride was responsible for the impaired renal handling of sodium that is often observed in patients with Bartter's syndrome. It appears that the reciprocal translocation is unrelated to both CAH and Bartter's syndrome since the same translocation was found in her healthy mother and siblings.