Ultrasonography monitoring with Superb Microvascular Imaging during cerebrovascular surgery.

INTRODUCTION: Ultrasonography (US) is used as a real-time dynamic imaging modality during neurosurgery. A novel Doppler US technique, Superb Microvascular Imaging (SMI), can be used to visualize low-velocity flow of small vessels at high resolution with high frame rates. We visualized vessel flow using this US SMI technique and contrast agent during cerebrovascular surgery. METHODS: Forty-three patients with an unruptured cerebral aneurysm (control), ischemic and hemorrhagic moyamoya disease, carotid artery stenosis, hemangioblastoma, severe stenosis of the middle cerebral artery, venous angioma, and intracerebral hemorrhage (ICH) underwent neurosurgery with US SMI monitoring using a contrast agent. The diameter, length, and number of penetrating vessels were analyzed in patients with an unruptured cerebral aneurysm (control), moyamoya disease, and ICH. RESULTS: Diameter and length of cerebral penetrating vessels were significantly increased in patients with moyamoya disease and ICH compared to control patients. The number of penetrating vessels was increased in moyamoya disease patients compared to control and ICH patients. In hemorrhagic moyamoya disease, flow in the penetrating vessels originated from a deep periventricular point and extended to the cerebral surface. Pulsatile cerebral aneurysms during clipping surgery and carotid artery stenosis during carotid endarterectomy were easily identified by SMI. Drastically increased vessel flow in patients with a hemangioblastoma or a venous angioma was observed. CONCLUSION: Using the US SMI technique and contrast agent, we obtained useful flow information of the vascular disease structure and intracerebral deep small vessels during cerebrovascular surgery. Further quantitative analysis will be informative and helpful for cerebrovascular surgery.

The Early Postoperative Course of Cognitive Function and Preoperative Cerebrovascular Reserve.

BACKGROUND: Patients with severe steno-occlusive disease of a main cerebral artery without causative lesions on magnetic resonance imaging (MRI) often develop cognitive impairment. However, the effects of revascularization surgery and the source of the cognitive impairment remain unclear. Therefore, we investigated the early postoperative course of cognitive function and its association with cerebral blood flow (CBF), cerebrovascular reserve (CVR), white matter disease (WMD), lacunar infarction, and cerebrovascular risk factors. METHODS: Cognitive function was examined using neurobehavioral cognitive status examination (COGNISTAT) in 52 patients with steno-occlusive disease of a main cerebral artery before and at 6 months after superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. We examined how cognition changed before and at 1, 3, and 6 months after STA-MCA anastomosis in 27 of 52 patients. CVR and CBF were calculated from 123I-N-isopropyl-p-iodoamphetamine single photon emission computed tomography, in addition to other cerebrovascular risk factors in 34 of 52 patients. Cerebral infarction and WMD (periventricular hyperintensity [PVH] and deep subcortical white matter hyperintensity) were also evaluated preoperatively by MRI. RESULTS: COGNISTAT scores improved at 1 month after STA-MCA anastomosis in patients with severe steno-occlusive disease of a main cerebral artery. Multiple stepwise regression analysis revealed that CVR (regression coefficient = -2.237, p = 0.0020) and PVH (regression coefficient = 2.364, p = 0.0029) were the best predictors of postoperative improvement in COGNISTAT scores (R 2 = 0.415; p = 0.0017). CONCLUSION: Cognitive function improves in relation to preoperative CVR and PVH early after STA-MCA anastomosis in patients with steno-occlusive disease of a main cerebral artery.

Neurosurgical intraoperative ultrasonography using contrast enhanced superb microvascular imaging -vessel density and appearance time of the contrast agent.

BACKGROUND: Ultrasonography (US) provides real-time information on structures within the skull during neurosurgical operations. Superb microvascular imaging (SMI) is the latest imaging technique for detecting very low-velocity flow with minimal motion artifacts, and we have reported on this technique for intraoperative US monitoring. We combined SMI with administration of contrast agent to obtain detailed information during neurosurgical operations. MATERIALS AND METHODS: Twenty patients diagnosed with brain tumor (10 meningiomas, 5 glioblastomas, 2 hemangioblastomas, 1 schwannoma, 1 malignant lymphoma, 1 brain abscess) underwent neurosurgery under US with SMI and contrast agent techniques. Vessel density and appearance time following contrast administration were analyzed. RESULTS: Flow in numerous vessels was not visualized by SMI alone, but appeared following injection of contrast agent in all cases. Flow in tumors was drastically enhanced by contrast agent in schwannoma, hemangioblastoma and meningioma, compared to normal brain tissue. Flows in the dilated and bent vessels of glioblastoma were also enhanced, although flow in hypoechoic lymphoma remained inconspicuous. The characteristics of tumor vessels were clearly visualized and tumor borders were demonstrated by the difference between tumor flow and brain flow, by the increased tumor vessel density and decreased appearance time of contrast agent compared to normal brain vessels. CONCLUSIONS: The combination of SMI and contrast agent techniques for intraoperative US monitoring could provide innovative flow images of tumor and normal brain. The neurosurgeon obtains information about tumor flow and tumor borderline before tumor resection.

Initial Progressions of Carotid Artery Plaque Are Associated with Risk Factors of Cardiovascular Disease.

BACKGROUND: Carotid artery plaque, white matter disease (WMD), and silent lacunae infarcts (initial indicators) are associated with symptomatic cerebral infarction (CI) caused by atherosclerosis. We retrospectively examined the association between the initial indicators and risk factors for cerebrovascular disease, considering the primary prevention of symptomatic CI. METHODS: We divided 1503 individuals who were neurologically healthy and enrolled in a brain screening program (brain dock) at our institution, into three initial plaque grades (grade 0, 1, and 2) based on having no plaques, having plaques on the right or left carotid artery, or having plaques on both carotid arteries, respectively. We analyzed the risk factors according to the presence/absence of the initial indicators. RESULTS: WMD and the risk factors (low-density lipoprotein [LDL], hemoglobin A1c, systolic blood pressure [BP], and smoking cigarettes) were positively correlated with the initial plaque grades, even when their laboratory values were within normal ranges. Systolic BP (116.5 ± 14.0 mmHg) was significantly lower in group 00 (without carotid plaque and WMD) than that in age-adjusted others (with carotid plaque or WMD). In young participants aged between 40 and 52 years, LDL (132.8 ± 24.5 mg/dl) was significantly higher in subgroup ++ (with carotid plaque and WMD) compared to others (without carotid plaque or WMD). CONCLUSION: Initial plaque grade and WMD grade as clinical initial indicators of symptomatic CI are associated with risk factors. To avoid deterioration of the initial indicators, it was suggested that the risk factors should be maintained at the lower ends of normal ranges and smoking cessation should be recommended.

Endoscopic ultrasound imaging with high flow mode for endonasal transsphenoidal pituitary surgery.

Intraoperative ultrasound during transsphenoidal surgery (TSS) for pituitary tumors has been reported. In reports of endonasal ultrasound (US), Doppler US vessel images were informative and effective in endoscopic TSS. We performed endoscopic US imaging with high flow mode, which is a novel technology, to visualize small vessels during endonasal endoscopic TSS. Six patients (five with pituitary adenomas and one with Rathoke's cleft cyst) underwent endoscopic US-assisted TSS. A small endoscopic US probe (Olympus, BF-UC260FW; diameter, 6.9 mm) was inserted transsphenoidally to the sellar floor and into the sella turcica, and endoscopic US monitoring was performed. By rotating the endoscopic US probe, the internal carotid artery, anterior cerebral artery, middle cerebral artery, various small vessels, optic nerve, and residual tumor were clearly visualized on the endoscopic US images. Real-time animated vessel images around the tumor could be generated when needed during TSS. The tumors were removed without leakage of cerebrospinal fluid in the six patients, and their visual acuity was restored. Endoscopic US with high flow mode can visualize not only main cerebral arteries but also intracranial small vessels on B-mode US images. Pituitary tumors were clearly recognized and removed safely and precisely by monitoring the cerebral artery and its small branches as landmarks.

Characterization of stable hypoxia-preconditioned dental pulp stem cells compared with mobilized dental pulp stem cells for application for pulp regenerative therapy.

BACKGROUND: Dental pulp stem cells (DPSCs) have been developed as a potential source of mesenchymal stem cells (MSCs) for regeneration of dental pulp and other tissues. However, further strategies to isolate highly functional DPSCs beyond the colony-forming methods are required. We have demonstrated the safety and efficacy of DPSCs isolated by G-CSF-induced mobilization and cultured under normoxia (mobilized DPSCs, MDPSCs) for pulp regeneration. The device for isolation of MDPSCs, however, is not cost-effective and requires a prolonged cell culture period. It is well known that MSCs cultured under hypoxic-preconditions improved MSC proliferation activity and stemness. Therefore, in this investigation, we attempted to improve the clinical utility of DPSCs by hypoxia-preconditioned DPSCs (hpDPSCs) compared with MDPSCs to improve the potential clinical utility for pulp regeneration in endodontic dentistry. METHODS: Colony-forming DPSCs were isolated and preconditioned with hypoxia in a stable closed cultured system and compared with MDPSCs isolated from the individual dog teeth. We examined the proliferation rate, migration potential, anti-apoptotic activity, and gene expression of the stem cell markers and angiogenic/neurotrophic factors. Trophic effects of the conditioned medium (CM) were also evaluated. In addition, the expression of immunomodulatory molecules upon stimulation with IFN-γ was investigated. The pulp regenerative potential and transplantation safety of hpDPSCs were further assessed in pulpectomized teeth in dogs by histological and immunohistochemical analyses and by chemistry of the blood and urine tests. RESULTS: hpDPSCs demonstrated higher proliferation rate and expression of a major regulator of oxygen homeostasis, HIF-1α, and a stem cell marker, CXCR-4. The direct migratory activity of hpDPSCs in response to G-CSF was significantly higher than MDPSCs. The CM of hpDPSCs stimulated neurite extension. However, there were no changes in angiogenic, migration, and anti-apoptotic activities compared with the CM of MDPSCs. The expression of immunomodulatory gene, PTGE was significantly upregulated by IFN gamma in hpDPSCs compared with MDPSCs. However, no difference in nitric oxide was observed. The regenerated pulp tissue was quantitatively and qualitatively similar in hpDPSC transplants compared with MDPSC transplants in dog teeth. There was no evidence of toxicity or adverse events of the hpDPSC transplantation. CONCLUSIONS: These results demonstrated that the efficacy of hpDPSCs for pulp regeneration was identical, although hpDPSCs improved stem cell properties compared to MDPSCs, suggesting their potential clinical utility for pulp regeneration.

Dermal Fibroblasts Internalize Phosphatidylserine-Exposed Secretory Melanosome Clusters and Apoptotic Melanocytes.

Pigmentation in the dermis is known to be caused by melanophages, defined as melanosome-laden macrophages. In this study, we show that dermal fibroblasts also have an ability to uptake melanosomes and apoptotic melanocytes. We have previously demonstrated that normal human melanocytes constantly secrete melanosome clusters from various sites of their dendrites. After adding secreted melanosome clusters collected from the culture medium of melanocytes, time-lapse imaging showed that fibroblasts actively attached to the secreted melanosome clusters and incorporated them. Annexin V staining revealed that phosphatidylserine (PtdSer), which is known as an 'eat-me' signal that triggers the internalization of apoptotic cells by macrophages, is exposed on the surface of secreted melanosome clusters. Dermal fibroblasts were able to uptake secreted melanosome clusters as did macrophages, and those fibroblasts express TIM4, a receptor for PtdSer-mediated endocytosis. Further, co-cultures of fibroblasts and melanocytes demonstrated that dermal fibroblasts internalize PtdSer-exposed apoptotic melanocytes. These results suggest that not only macrophages, but also dermal fibroblasts contribute to the collection of potentially toxic substances in the dermis, such as secreted melanosome clusters and apoptotic melanocytes, that have been occasionally observed to drop down into the dermis from the epidermis.

Comparison of Macrophage Activation Using γ-Globulin and Serum-derived Macrophage Activating Factor.

BACKGROUND/AIM: Serum-derived macrophage activating factor (serum-MAF) can rapidly activate macrophage phagocytic activity by inducing characteristic membrane ruffles designated as Frill-like structures. Serum-MAF contains γ-globulin, an activator of phagocytosis. This study examined whether serum-MAF and γ-globulin activate macrophages similarly. MATERIALS AND METHODS: Morphological changes in macrophages were observed by time-lapse imaging and the efficiency of engulfment was analysed quantitatively. Immunological staining of talin-1 and a calpain inhibitor were performed. RESULTS: The engulfment efficiency of serum-MAF- and γ-globulin-activated macrophages was significantly different. Talin-1 showed weak co-localisation with the Frill-like structures. Treatment with a calpain inhibitor similarly down-regulated phagocytosis irrespective of the activation factor. CONCLUSION: There was a difference between macrophage activation mechanisms by γ-globulin and serum-MAF. Talin may slightly contribute to serum-MAF activation. It is possible to distinguish between the calpain-dependent fundamental 'mechanism of phagocytosis' and the activating factor-dependent rapid 'activation mechanism'.

Ultrasonographic superb microvascular imaging for emergency surgery of intracerebral hemorrhage.

Ultrasonography (US) has been used as a reliable imaging modality, providing real-time information during neurosurgical operations. One recent innovative US technique, superb microvascular imaging (SMI), visualizes small vessels and flow, which are not detected with standard US with doppler. We apply SMI to intraoperative US monitoring in emergency surgery for intracerebral hemorrhage (ICH). Eleven consecutive patients with ICH underwent endoscopic emergency surgery under US monitoring with SMI. After performing a small craniotomy, US images were obtained using SMI, a fusion technique, and a contrast agent technique, with the probe on the brain surface during surgery. Fusion images were obtained with the probe on the head before craniotomy in some patients. Animated US images with SMI could differentiate hematoma containing no vessels from brain tissue, and flow images using SMI and contrast agent techniques clarified the borderlines. Animated fusion images of intraoperative US and preoperative CT provided information on the extent of hematoma and residual hematoma during emergency surgery. We made various fusion CT images showing intracranial hematoma with US probes and decided on the skin incision line before beginning surgery, as if we were using a neuronavigation system. US with SMI, contrast agent, and fusion techniques provide information on the extent of intracranial hematoma and residual hematoma with no vessels and no flow. Monitoring by US and fusion CT images is useful for ICH surgery as a next-generation neuronavigator.

Characteristic Morphological Changes and Rapid Actin Accumulation in Serum-MAF-treated Macrophages.

BACKGROUND/AIM: Serum-derived macrophage activating factor, serum-MAF, is known to increase the phagocytic activity of macrophages by enhancing the engulfment efficiency. To elucidate the mechanisms underlying phagocytic activation, morphological changes were observed and analyzed. MATERIALS AND METHODS: Morphological changes in macrophages were observed and quantitatively analyzed using scanning electron microscope (SEM) and confocal microscope. RESULTS: SEM and confocal microscopy images revealed frill-like structures and active actin accumulations, respectively, in serum-MAF treated macrophages. Actin accumulation was induced within 5 min following serum-MAF treatment. CONCLUSION: Serum-MAF induced a rapid rearrangement of cytoskeletal actin and enhanced phagocytic activity. Findings of the current study may contribute to the development of techniques that facilitate activation of the human immune system, which in turn may be beneficial for cancer immunotherapy.

Phagocytic Activation of Macrophages with Serum MAF Depends on Engulfment Efficiency and Not Migratory Activity.

BACKGROUND/AIM: Serum-derived macrophage activating factor (serum MAF) is known to increase the phagocytic activity of macrophages and potentially plays a role in activating cancer immunity. In order to reveal the contributing factors for phagocytic activation, the migratory activity and the efficiency of engulfment was analyzed. MATERIALS AND METHODS: THP-1 macrophages were induced by 12-O-tetradecanoyl-13-acetate (TPA). The migratory activity and efficiency of engulfment were analyzed by time-lapse imaging and suspension assay, respectively. RESULTS: While the distance of migration did not change before and after activation with serum MAF, the efficiency of beads internalisation was significantly increased. CONCLUSION: Phagocytic activation of serum-MAF-treated macrophages was caused by increasing the efficiency of engulfment. This study contributes to the knowledge about the activation of the immune system through phagocytic activation of macrophages.

Intraoperative Hypoglossal Nerve Mapping During Carotid Endarterectomy: Technical Note.

BACKGROUND: Hypoglossal nerve deficit is a possible complication caused by carotid endarterectomy (CEA). The accidental injury of the hypoglossal nerve during surgery is one of the major reasons for permanent hypoglossal nerve palsy. In this study, we investigated the usefulness of intraoperative mapping of the hypoglossal nerve to identify this nerve during CEA. METHODS: Five consecutive patients who underwent CEA for the treatment of symptomatic or asymptomatic carotid artery stenosis were studied. A hand-held probe was used to detect the hypoglossal nerve in the operative field, and the tongue motor evoked potentials (MEPs) were recorded. RESULTS: The tongue MEPs were obtained in all the patients. The invisible hypoglossal nerve was successfully identified without any difficulty when the internal carotid artery was exposed. Intraoperative mapping was particularly useful for identifying the hypoglossal nerve when the hypoglossal nerve passed beneath the posterior belly of the digastric muscle. In 1 of 2 cases, MEP was also elicited when the ansa cervicalis was stimulated, although the resulting amplitude was much smaller than that obtained by direct stimulation of the hypoglossal nerve. Postoperatively, none of the patients presented with hypoglossal nerve palsy. CONCLUSIONS: Intraoperative hypoglossal nerve mapping enabled us to locate the invisible hypoglossal nerve during the exposure of the internal carotid artery accurately without retracting the posterior belly of the digastric muscle and other tissues in the vicinity of the internal carotid artery.

Cochlear Nerve Action Potential Monitoring for Preserving Function of an Unseen Cochlear Nerve in Vestibular Schwannoma Surgery.

BACKGROUND: Intraoperative monitoring of cochlear nerve action potential (CNAP) has been used in patients with small vestibular schwannoma (<15 mm) to preserve cochlear nerve function. We performed surgery for a larger vestibular schwannoma under CNAP monitoring with the aim of preserving cochlear nerve function, and compared the data with findings from 10 patients with hemifacial spasm who underwent microvascular decompression surgery. CASE DESCRIPTION: We report the case of a patient with a 26-mm vestibular schwannoma and normal hearing function who underwent neurosurgery under electrophysiological monitoring of the facial and cochlear nerves. Amplitudes of evoked facial muscle responses were maintained at approximately 70% during the operation. The latency of wave V on brainstem auditory evoked potential (BAEP) increased by 0.5 ms, and amplitude was maintained at approximately 70% of the value at the beginning of the operation. Latencies of P1, N1, and P2 on CNAP did not change intraoperatively. These latencies were comparable to those of 10 normal patients with hemifacial spasm. CNAP monitoring proved very useful in confirming the location of the cochlear nerve in the operative field and preserving cochlear nerve function. Both facial nerve function and hearing acuity were completely preserved after tumor removal, and wave V latency on BAEP returned to normal and was maintained in the normal range for at least 2 years. CONCLUSIONS: CNAP monitoring is extremely useful for preserving the function of the unseen cochlear nerve during vestibular schwannoma surgery.

Exploration of the Most Effective Dural Incision Design in a Decompressive Craniectomy.

OBJECTIVE: During a decompressive craniectomy performed for a severe cerebral infarction, sufficient coverage of the underlying bulging brain by converting the flat dura mater to a more domelike shape is essential. In this procedure, suturing to patch dural substitutes on the dural rifts occupies most of the operative time and is cumbersome. We present a new dural incision design that provides an appropriate volume of subdural space with minimal incisions. METHODS: The ideal incision design was geometrically analyzed and verified by simulations using a physics engine. RESULTS: Assuming a quadrilateral area on the dura mater surface termed S, expanding the entire area of S requires 2d (where d is the skull thickness) + a 30-mm extension of the shortest set of line segments connecting each vertex (LSCV) of S to cover the necessary volume of bulging brain. The shortest LSCV comprises 5 line segments connected with two 3-pronged intersections. The ideal incision design consists of a pair of curved line segments that maintain plane continuity along the LSCV, which automatically limits the maximum expansion. The ideal incision design of S consists of 5 uncinate line segments. Four of the line segments originate from each vertex of S and end by crossing over the LSCV, and one of the line segments crosses over 2 separate LSCV. A representative case is shown. CONCLUSIONS: This technique minimizes the complexity of the operation and shortens the operation time.

Ultrasonography Monitoring with Superb Microvascular Imaging Technique in Brain Tumor Surgery.

BACKGROUND: Neuronavigation based on preoperative magnetic resonance imaging has been developed as a useful tool to improve visibility of the surgical site in the operative field. Ultrasonography (US) monitoring has also been used as a reliable imaging technique, providing real-time information during neurosurgical operations. We combined the latest innovative imaging technique for detecting very low-flow components, Superb Microvascular Imaging (SMI), with US monitoring during brain tumor surgery. CASE DESCRIPTION: Fifteen patients diagnosed with brain tumor (8 malignant and 7 benign) underwent neurosurgery with US monitoring using an Aplio 400/500 US system with the new SMI technique (imaging frequency, 10-12 MHz; frame rate, 28-31 Hz). Features of the SMI images in the gray scale mode include 1) visualization of low-velocity flow with minimal motion artifact, 2) high resolution of images, and 3) high frame rates. The tumors, tumor vessels, compressed and shifted healthy vessels, and cistern were clearly visualized on the SMI images in the gray scale mode, detailing the characteristics of healthy brain tissue (vertically penetrating, fine, straight vessels), glioblastoma (rounding, dilating, and bending vessels), low-grade glioma (fine and straight vessels), meningioma (many large and branching vessels), and lymphoma (less vascular, low echoic tumor) and demonstrating the tumor-defined border. We also performed biopsies under US monitoring with SMI. CONCLUSIONS: We combined SMI technique with US monitoring during brain tumor surgery and observed healthy and tumor vessels. Further research is important for the development of a more precise and reliable neurosurgery.

Macrophages Exhibit a Large Repertoire of Activation States via Multiple Mechanisms of Macrophage-activating Factors.

BACKGROUND/AIM: Macrophages are important components of human defense systems and consequently key to antitumor immunity. Human-serum macrophage activation factor (serum MAF) can activate macrophages, making it a promising reagent for anticancer therapy. MATERIALS AND METHODS: We established four different macrophage subtypes through introduction of different culture conditions to THP-1- and U937-derived macrophages. We assessed phagocytic activity to understand subtype responses to typical macrophage activation factors (MAFs) and the activation mechanisms of serum MAF. RESULTS: All four macrophage subtypes differed in their response to all MAFs. Moreover, serum MAF had two different activation mechanisms: N-acetylgalactosamine (GalNAc)-dependent and GalNAc-independent. CONCLUSION: Macrophage activation states and mechanisms are heterogeneous.

Leukocyte plugging and cortical capillary flow after subarachnoid hemorrhage.

BACKGROUND: It is believed that increased intracranial pressure immediately after subarachnoid hemorrhage (SAH) causes extensive brain ischemia and results in worsening clinical status. Arterial flow to the cerebral surfaces is clinically well maintained during clipping surgery regardless of the severity of the World Federation of Neurological Societies grade after SAH. To explore what kinds of changes occur in the cortical microcirculation, not at the cerebral surface, we examined cortical microcirculation after SAH using two-photon laser scanning microscopy (TPLSM). METHODS: SAH was induced in mice with an endovascular perforation model. Following continuous injection of rhodamine 6G, velocities of labeled platelets and leukocytes and unlabeled red blood cells (RBCs) were measured in the cortical capillaries 60 min after SAH with a line-scan method using TPLSM, and the data were compared to a sham group and P-selectin monoclonal antibody-treated group. RESULTS: Velocities of leukocytes, platelets, and RBCs in capillaries decreased significantly 60 min after SAH. Rolling and adherent leukocytes suddenly prevented other blood cells from flowing in the capillaries. Flowing blood cells also decreased significantly in each capillary after SAH. This no-reflow phenomenon induced by plugging leukocytes was often observed in the SAH group but not in the sham group. The decreased velocities of blood cells were reversed by pretreatment with the monoclonal antibody of P-selection, an adhesion molecule expressed on the surfaces of both endothelial cells and platelets. CONCLUSIONS: SAH caused sudden worsening of cortical microcirculation at the onset. Leukocyte plugging in capillaries is one of the reasons why cortical microcirculation is aggravated after SAH.

Macrophage Activation Mechanisms in Human Monocytic Cell Line-derived Macrophages.

BACKGROUND: Although the mechanisms of macrophage activation are important for cancer immunotherapy, they are poorly understood. Recently, easy and robust assay systems for assessing the macrophage-activating factor (MAF) using monocytic cell line-derived macrophages were established. MATERIALS AND METHODS: Gene-expression profiles of U937- and THP-1-derived macrophages were compared using gene expression microarray analysis and their responses against several MAFs were examined by in vitro experiments. RESULTS: Activated states of these macrophages could not be assigned to a specific sub-type but showed, however, different unique characteristics. CONCLUSION: The unique of monocytic cell line-derived macrophages could provide clues to understand the activation mechanism of macrophages and, therefore, help to develop effective cancer immunotherapy with MAFs.

Establishment of a Macrophage-activating Factor Assay System Using the Human Monocytic Cell Line THP-1.

BACKGROUND: As the mechanism of macrophage activation is not well-understood, standardization of an assay system for measuring phagocytic activities of macrophages will be useful for research on macrophages. Previously, we established a novel standardized macrophage-activating factor (MAF) assay system using U937. MATERIALS AND METHODS: Using the human monocytic cell line THP-1, another standardized MAF assay system was established. Characteristic gene expression of U937- and THP-1-derived macrophages was compared by gene expression microarray analysis. RESULTS: Both U937- and THP-1-derived macrophages showed obvious phagocytic activities with unique characteristics and, therefore, could not be assigned to a single sub-type. CONCLUSION: Activation of macrophages is an intricate cellular process. Comparison of our two novel assay systems provides new insights into macrophage activation mechanisms.

Endonasal ultrasonography-assisted neuroendoscopic transsphenoidal surgery.

We report endonasal ultrasonography (US)-assisted neuroendoscopic transsphenoidal surgery (TSS) in seven patients. With sagittal and coronal US images, internal carotid arteries, anterior cerebral arteries, residual tumor, and lateral ventricles were recognized, and the tumors were removed without leakage of cerebrospinal fluid in patients with pituitary adenoma. US images clearly depicted the carotid arteries, anterior cerebral arteries, middle cerebral arteries, chiasmatic cistern, and residual tumor. Endonasal US images can provide real-time animated information and may help neuroendoscopic TSS, whenever needed during TSS.