Acute Magnetic Resonance Imaging Findings in Young Children With Moyamoya Disease.

BACKGROUND: To describe the diffusion-weighted imaging (DWI) findings in young children with moyamoya disease (MMD) during the acute period of the condition. METHODS: Clinical data were collected from 12 children with MMD aged less than six years, in whom abnormalities were observed on DWI scans obtained within one week after the appearance of symptoms related to MMD. The DWI abnormalities were classified into gyral, atypical territorial, honeycomb, classical territorial, multiple-dot, border zone, and deep lacunar patterns. The severity of arterial stenosis was graded by angiographic stages that have been previously described. RESULTS: In all but one child, the DWI abnormalities were restricted to the cerebral cortex. The lesions were gyral in nature in seven children and atypical territorial in five; all differed from those of typical arterial strokes. Internal carotid artery stenosis was observed in all 12 children, although the stenosis was mild in 11. The severity of arterial stenosis did not match the regions of ischemic lesions in some children. There was no statistically significant difference in the severity of arterial stenosis according to the presence or absence of ischemic lesions or the pattern of the lesions. CONCLUSIONS: Lesions located mainly in the cerebral cortex, i.e., not in arterial territories, are characteristic of young children with MMD.

Development and validation of machine learning models to predict postoperative infarction in moyamoya disease.

OBJECTIVE: Cerebral infarction is a common complication in patients undergoing revascularization surgery for moyamoya disease (MMD). Although previous statistical evaluations have identified several risk factors for postoperative brain ischemia, the ability to predict its occurrence based on these limited predictors remains inadequately explored. This study aimed to assess the feasibility of machine learning algorithms for predicting cerebral infarction after revascularization surgery in patients with MMD. METHODS: This retrospective study was conducted across two centers and harnessed data from 512 patients with MMD who had undergone revascularization surgery. The patient cohort was partitioned into internal and external datasets. Using perioperative clinical data from the internal cohort, three distinct machine learning algorithms-namely the support vector machine, random forest, and light gradient-boosting machine models-were trained and cross-validated to predict the occurrence of postoperative cerebral infarction. Predictive performance validity was subsequently assessed using an external dataset. Shapley additive explanations (SHAP) analysis was conducted to augment the prediction model's transparency and to quantify the impact of each input variable on shaping both the aggregate and individual patient predictions. RESULTS: In the cohort of 512 patients, 33 (6.4%) experienced postrevascularization cerebral infarction. The cross-validation outcomes revealed that, among the three models, the support vector machine model achieved the largest area under the receiver operating characteristic curve (ROC-AUC) at mean ± SD 0.785 ± 0.052. Notably, during external validation, the light gradient-boosting machine model exhibited the highest accuracy at 0.903 and the largest ROC-AUC at 0.710. The top-performing prediction model utilized five input variables: postoperative serum gamma-glutamyl transpeptidase value, positive posterior cerebral artery (PCA) involvement on preoperative MRA, infarction as the rationale for surgery, presence of an infarction scar on preoperative MRI, and preoperative modified Rankin Scale score. Furthermore, the SHAP analysis identified presence of PCA involvement, infarction as the rationale for surgery, and presence of an infarction scar on preoperative MRI as positive influences on postoperative cerebral infarction. CONCLUSIONS: This study indicates the usefulness of employing machine learning techniques with routine perioperative data to predict the occurrence of cerebral infarction after revascularization procedures in patients with MMD.

Safety of antiplatelet therapy during the perioperative period of revascularization surgery for moyamoya disease patients with ischemic onset.

For patients with moyamoya disease, antiplatelet agents are often used during the perioperative periods of revascularization surgeries to prevent ischemic events. However, antiplatelet therapy is associated with the risk of hemorrhagic complications. Further, the influence of antiplatelet therapy on perioperative ischemic or hemorrhagic complications has not been investigated. This study aimed to determine the impact of antiplatelet agents on adult moyamoya disease patients with ischemic onset during the perioperative period. From January 2016 to December 2020, 183 consecutive combined (direct and indirect) revascularization surgeries for moyamoya disease patients were performed. Among these surgeries, 96 consecutive combined revascularization surgeries for adult moyamoya disease patients with ischemic onset were analyzed and perioperative ischemic and hemorrhagic complications were reviewed. Antiplatelet agents were continued during the perioperative period including on the day of surgery and the day after the surgery. Among 96 surgeries, no hemorrhagic complications occurred postoperatively. Infarction occurred in five cases (5.2%). Among the five cases, neurological deficits persisted in two cases and improved in three. The median value of bleeding volume was 112.5 mL (interquartile range, 80.0 - 200.0). Twenty-five cases (26.0%) needed blood transfusion. The modified Rankin Scale score deteriorated in two cases due to cerebral infarction. The incidence of hemorrhagic and ischemic complications after combined revascularization surgery in patients with ischemic moyamoya disease under antiplatelet therapy was low, indicating the safety of continued antiplatelet therapy.

Higher abundance of Campylobacter in the oral microbiome of Japanese patients with moyamoya disease.

Genetic factors alone cannot explain the pathophysiology of moyamoya disease (MMD), and environmental factors such as an immune response are thought to be involved. Oral and gut microbiomes have attracted attention as environmental factors in the pathophysiology of some vascular and autoimmune diseases. However, the relationship between MMD and these microbiomes is yet to be thoroughly investigated. This prospective case-control study aimed to compare the microbiomes of Japanese patients with MMD with those of healthy individuals to identify the specific bacteria involved in MMD. Saliva and fecal samples were collected from 16 patients with MMD who had not undergone revascularization surgery. Fifteen healthy individuals were matched for age, sex, and body mass index. The microbiomes were determined using 16S rRNA sequencing and analyzed using QIIME2. Differentially abundant microbes were identified using LEfSE and ANCOM-BC. In the oral microbiome, the two analytical methods showed that Campylobacter was more abundant in patients with MMD than in healthy individuals. Differences in the gut microbiome were smaller than those in the oral microbiome. In conclusion, the oral microbiome profiles of patients with MMD significantly differ from those of healthy individuals. Campylobacter spp. could be a substantial environmental factor in the pathophysiology of MMD.

Ruptured proximal middle cerebral artery traumatic pseudoaneurysm treated with bypass-assisted trapping surgery: A case report.

Background: Traumatic pseudoaneurysms are rare but have a high mortality rate; therefore, immediate diagnosis is vital. Most pseudoaneurysms are in the internal carotid artery or peripheral arteries, while proximal middle cerebral artery pseudoaneurysms have rarely been reported. We present a case of ruptured traumatic pseudoaneurysm located at the M1-M2 bifurcation. Case Description: A 42-year-old man was injured in a motorcycle accident and his Glasgow coma scale score on admission was 7 (Eye opening1, Verbal response2, Motor response4 [E1V2M4]). Head computed tomography (CT) showed thick subarachnoid hemorrhage (SAH). We suspected a ruptured aneurysm, but three-dimensional CT angiography (3D-CTA) did not detect any vascular defects. Head magnetic resonance angiography showed progressive right M1 stenosis suggesting arterial dissection. 3D-CTA on day 20 showed a small aneurysm in the proximal portion of the M2. Although surgery was scheduled for day 26, suddenly left hemiparesis appeared on day 24. Head CT detected fresh SAH and emergency surgery was performed on day 25. We dissected around the ruptured point under M1 temporary occlusion with superficial temporal artery-M2 assist bypass. Contrary to our expectations, there was only a small laceration in the right M2 superior trunk. We trapped the laceration and the proximal portion of the M2 superior trunk while preserving antegrade blood flow from the M1 to the M2 inferior trunk. On the 5-month follow-up, the patient was able to walk independently. Conclusion: Unreasonably thick traumatic SAH or spastic stenosis after head injury may indicate a traumatic pseudoaneurysm and require repeated neurovascular evaluation. If a pseudoaneurysm is detected, immediate surgical intervention is mandatory.

Complex aneurysm formation in the proximal segment of the posterior cerebral artery: a report of two cases.

Posterior cerebral artery (PCA) aneurysms are rare and often fusiform. We describe two cases of complex proximal PCA aneurysm in two women in their 60's, which probably resulted from segmental arterial degeneration. Both presented with subarachnoid hemorrhage and had common angiographic and intraoperative findings: tortuous configuration of the affected P1 segment, whitish or yellowish appearance of a portion of the lesion, lesion calcification, and multiple aneurysms in the segment. Interestingly, no significant atherosclerotic changes were noted in other cerebral arteries. The ruptured aneurysm could be successfully trapped, with superficial temporal artery (STA)-PCA bypass in one and without bypass in the other, and both patients recovered well. As complex aneurysm formation in the cases described here are probably related to proximal PCA segmental degeneration, we recommend trapping the lesion, with or without STA-PCA bypass, depending on the size and patency of the posterior communicating artery.

Effects of superficial temporal artery to middle cerebral artery bypass on postoperative infarction rates among young children (≤ 5 years old) with moyamoya disease.

Revascularization surgery for young children with moyamoya disease (MMD) is challenging. Although indirect revascularization is preferred because of the technical difficulty in direct anastomosis, higher risks of postoperative infarction remain a problem. We aimed to investigate the effect of superficial temporal artery to middle cerebral artery (STA-MCA) bypass on postoperative outcomes during the acute postoperative period in young children ≤ 5 years old with MMD. This retrospective study included consecutive young children with MMD who underwent surgical revascularization of the anterior cerebral circulation. Groups were determined according to the procedures performed, namely, the combined (STA-MCA bypass with indirect revascularization) and the indirect revascularization groups. The incidences of radiological or symptomatic infarction, transient neurological events, and new neurological deficits that remained at discharge were compared between groups. Of 38 surgical procedures, there were 23 combined and 15 indirect revascularizations. The median age of the patients was 3.0 years, which was significantly different between groups (P < .01). When comparing the postoperative outcomes between groups, the incidences of radiological and symptomatic infarction and new neurological deficits that remained at discharge were significantly lower in the combined revascularization group (P < .05). Logistic regression analysis adjusted for potential confounders found that surgical modality was a statistically significant independent risk factor associated with radiological and symptomatic infarctions (indirect/combined, odds ratio: 10.2; 95% confidence interval: 1.30-79.7; P < .05). STA-MCA bypass combined with indirect revascularization can reduce the incidence of postoperative infarction in young children with MMD and might lead to better neurological outcomes.

Rare Dilated Collateral Circulation from Accessory Meningeal Artery to Inferolateral Trunk: A Case Report.

The accessory meningeal artery (AMA) demonstrates various potential anastomoses with the external (ECA) and internal (ICA) carotid arteries. However, rarely does the AMA markedly dilate and compensate for ICA blood flow. A 52-year-old woman with nonspecific symptoms was diagnosed with multiple cerebral aneurysms and abnormal blood vessels observed on magnetic resonance angiography. Digital subtraction angiography revealed four aneurysms and anastomoses between the left AMA and inferolateral trunk (ILT). In addition, two sequential severe flexions were observed in the cervical portion of the left ICA. No ischemic lesions were detected on magnetic resonance imaging. In conclusion, we experienced a rare case in which the AMA-ILT anastomosis was highly developed. This case also presented with the unusual characteristics of an anomaly in the extracranial ICA and multiple aneurysms.

CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in primary central nervous system lymphoma.

BACKGROUND: Rituximab, high-dose methotrexate (HD-MTX), procarbazine and vincristine (R-MPV), has significantly prolonged the survival of patients with primary central nervous system lymphoma (PCNSL), but predictive factors for response to R-MPV have not yet been investigated. Herein, we investigated the correlation of MYD88 L265P and CD79B Y196 mutations, which are the most frequently found molecular alterations in PCNSL, with prognosis of patients with PCNSL treated with R-MPV. METHODS: We investigated the long-term clinical course and status of MYD88 and CD79B genes in 85 patients with PCNSL treated with R-MPV or HD-MTX treatment, and the correlation of these genetic mutations with prognosis. RESULTS: R-MPV achieved an excellent tumor control rate (61.6% and 69.9% of 5-year progression-free and overall survival rates, respectively). While MYD88 L265P mutation had no significant effect on survival, patients with CD79B Y196 mutations exhibited prolonged survival (p < 0.05). However, the association of CD79B Y196 mutation with a better prognosis was not observed in the HD-MTX cohort, which indicated that CD79B Y196 mutation was a predictive marker for a favorable response to R-MPV. Furthermore, we established an all-in-one rapid genotyping system for these genetic mutations. CONCLUSIONS: In conclusion, CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in PCNSL. The rapid identification of MYD88 L265P and CD79B Y196 mutations can be helpful not only for the accurate molecular diagnosis of PCNSL but also for the prediction of response to R-MPV.

Surgical disconnection of a hypoglossal canal dural arteriovenous fistula demonstrating rapid progression of medulla oblongata disturbance: illustrative case.

BACKGROUND: Dural arteriovenous fistulas of the hypoglossal canal (HCDAVFs) with dominant drainage to perimedullary veins are extremely rare. These patients are prone to develop slow and progressive myelopathy, however, their clinical course has not been fully elucidated. We report an unusual case of HCDAVF in which the patient demonstrated rapid progression of hemiplegia and respiratory insufficiency. OBSERVATIONS: An 82-year-old woman demonstrated motor weakness of the left extremities. T2-weighted magnetic resonance imaging showed a high intensity area in the right medulla oblongata and angiography revealed HCDAVF with dominant drainage to the anterior medullary vein through the anterior condylar vein. Within 3 days, her hemiparesis and respiratory function worsened, and she needed mechanical ventilation. Considering that venous congestion in the medulla oblongata could cause the symptoms, we immediately performed surgical obliteration of the anterior condylar vein. The disappearance of HCDAVF was confirmed by angiography and the patient was weaned from mechanical ventilation 3 days postoperatively. Her left hemiplegia gradually resolved and she was independent in daily life 8 months after the operation. LESSONS: HCDAVFs with dominant drainage to the perimedullary veins can demonstrate rapid progression of medulla oblongata disturbance. Early disconnection should be considered to provide an opportunity for substantial recovery.

Preventive Effect of Bypass Surgery on Rebleeding in Patients with Hemorrhagic Twiglike Middle Cerebral Artery.

BACKGROUND: Aplastic or twiglike middle cerebral artery (Ap/T-MCA) is a rare cerebrovascular anomaly correlated to stroke. The most common characteristic of the disease is intracerebral hemorrhage. However, treatment measures that can prevent rebleeding have not yet been established. OBJECTIVE: We sought to validate whether extracranial-intracranial (EC-IC) bypass is effective in preventing recurrent intracerebral hemorrhage in patients with Ap/T-MCA. METHODS: Ap/T-MCA was defined on the basis of the following criteria: 1) M1 occlusion with plexiform vessels, 2) unilateral MCA involvement without progression to the contralateral side, 3) no significant stenosis in the M2 segment, and 4) no stenoocclusive lesions in other intracranial major arteries. The clinical features, surgical procedures, radiologic changes, and treatment outcomes of patients with Ap/T-MCA who presented with ipsilateral intracerebral hemorrhage at our institution from April 2004 to December 2019 were retrospectively reviewed. RESULTS: Seven patients fulfilled the criteria for hemorrhagic Ap/T-MCA. Female preponderance was observed, and the mean age at the time of onset was 38 (range: 28-47) years. Three patients presented with pure intraventricular hemorrhage and 4 with intraparenchymal hemorrhage. Of the 4 patients, 2 had intraventricular extension. All patients underwent EC-IC bypass and did not present with stroke during the follow-up period (median: 36 [range: 5-140] months). Follow-up magnetic resonance imaging revealed regression of the twiglike vessels or periventricular choroidal anastomosis within 1 year after surgery in all patients. CONCLUSIONS: EC-IC bypass may be a treatment option that can prevent rebleeding in patients with hemorrhagic Ap/T-MCA.

Usefulness of Neuromelanin Sensitive MRI for En Plaque Meningeal Melanocytoma Involving the Cavernous Sinus: A Case Report.

Intracranial meningeal melanocytoma is a rare tumor. Here, we report a case of pathologically diagnosed en plaque meningeal melanocytoma involving the cavernous sinus along with a review of the pertinent literature. A 35-year-old female presented with progressing left oculomotor nerve palsy and melanosis oculi. Radiological examinations revealed a lesion spreading in an en plaque fashion and involving the left cavernous sinus, which was hyperintense on T1-weighted magnetic resonance imaging (MRI), and hypointense on T2-weighted MRI. The lesion was partially excised following a histopathological diagnosis of meningeal melanocytoma. For follow-up of the residual lesion, neuromelanin sensitive MRI was introduced, and it provided better contrast between the lesion and surrounding intracranial normal tissue than conventional T1-weighted MRI with or without gadolinium. The lesion remained stable without any growth for 3 years post-surgery. Neuromelanin sensitive MRI may be the method of choice for the follow-up of meningeal melanocytoma.

Progressive stenosis and radiological findings of vasculitis over the entire internal carotid artery in moyamoya vasculopathy associated with graves' disease: a case report and review of the literature.

BACKGROUND: Moyamoya vasculopathy (MMV) associated with Graves' disease (GD) is a rare condition resulting in ischemic stroke accompanied by thyrotoxicity. Radiological findings of vasculitis have been reported in the walls of distal internal carotid arteries (ICAs) in these patients; however, no reports have described in detail the processes of progression of the lesions in the proximal ICA. Moreover, treatments to prevent recurrence of ischemic stroke and progression of MMV have not yet been sufficiently elucidated. CASE PRESENTATION: We report a progressive case of MMV associated with GD and review the literature to clarify relationships among recurrence, progression, thyrotoxicity and treatment. Our patient developed cerebral infarction during thyrotoxicity with no obvious stenosis of ICAs. Five months later, transient ischemic attacks recurred with thyrotoxicity. Antiplatelet therapy and intravenous methylprednisolone stopped the attacks. Stenosis of the left ICA from the proximal to distal portion and champagne bottle neck sign (CBN) were found. She declined any surgery. Afterward, gradual progression with mild thyrotoxicity was observed. Eventually, we found smooth, circumferential, concentric wall thickening with diffuse gadolinium enhancement of the left ICA from the proximal to the distal portion on T1-weighted imaging, suggesting vasculitis radiologically. The clinical and radiological similarities to Takayasu arteritis encouraged us to provide treatment as for vasculitis of medium-to-large vessels. In a euthyroid state and after administration of prednisolone and methotrexate, improved flow in the cerebrovascular arteries on magnetic resonance angiography was observed. Based on our review of the literature, all cases with recurrence or progression were treated with anti-thyroid medication (ATM) alone and accompanied by thyrotoxicity. CBN was observed in all previous cases for which images of the proximal ICA were available. CONCLUSIONS: We report the details of progressive stenosis from a very early stage and radiological findings of vasculitis over the entire ICA in MMV associated with GD. Cerebral infarction can occur with no obvious stenosis of the ICA. We treated the patient as per vasculitis of a medium-to-large vessel. Management of GD by ATM alone seems risky in terms of recurrence. Adequate management of GD and possible vasculitis may be important for preventing recurrence and progression.

Long-Term Effects on Preventing Stroke after Endovascular Treatment or Bypass Surgery for Intracranial Arterial Stenosis.

BACKGROUND: Intracranial arterial stenosis (ICAS) is an important cause of ischemic stroke worldwide due to its higher risk of recurrence with medical therapy. Although some large randomized studies failed to show the superiority of surgical treatment compared with medical therapy, the results of medical therapy are not sufficient. There are patients who still benefit from surgical treatment. This retrospective analysis aimed to evaluate the long-term efficacy of surgical therapy with percutaneous transluminal angioplasty and/or stenting (PTA/PTAS) or extracranial-intracranial (EC/IC) bypass surgery for patients with ICAS. METHODS: Between October 2005 and December 2016, 55 ICAS patients were treated with PTA/PTAS or EC-IC bypass surgery. Their electronic medical records were retrospectively reviewed and analyzed. The primary outcome was all adverse events beyond 30 days after a revascularization procedure. RESULTS: We performed 21 cases (35%) of PTA, 4 cases (7%) of PTAS, and 34 cases (58%) of EC-IC bypass surgery and the median follow-up duration was 66 months (range 1-144 months). The occurrence rate of the primary outcome was 10.2% and only 1 patient (1.8%) experienced ipsilateral disabling ischemic stroke beyond 30 days. The long-term functional independent survival rate was 83.6%. CONCLUSIONS: We demonstrated a long-term favorable outcome of combined surgical intervention for ICAS patients with PTA/PTAS and EC-IC bypass surgery, and the result was better than previously reported outcomes of medical therapy. Additional multicenter studies are required to draw firm conclusions on the efficacy of reduction of recurrent stroke in patients with ICAS.

Tumor Volume Decrease via Feeder Occlusion for Treating a Large, Firm Trigone Meningioma.

Trigone meningiomas are considered a surgical challenge, as they tend to be considerably large and hypervascularized at the time of presentation. We experienced a case of a large and very hard trigone meningioma that was effectively treated using initial microsurgical feeder occlusion followed by surgery in stages. A 19-year-old woman who presented with loss of consciousness was referred to our hospital for surgical treatment of a brain tumor. Radiological findings were compatible with a left ventricular trigone meningioma extending laterally in proximity to the Sylvian fissure. At initial surgery using the transsylvian approach, main feeders originating from the anterior and lateral posterior choroidal arteries were occluded at the inferior horn; however, only a small section of the tumor could initially be removed because of its firmness. Over time, feeder occlusion resulted in tumor necrosis and a 20% decrease in its diameter; the mass effect was alleviated within 1 year. The residual meningioma was then totally excised in staged surgical procedures after resection became more feasible owing to ischemia-induced partial softening of the tumor. When a trigone meningioma is large and very hard, initial microsurgical feeder occlusion in the inferior horn can be a safe and effective option, and can lead to necrosis, volume decrease, and partial softening of the residual tumor to allow for its staged surgical excision.

Prevention of the Rerupture of Collateral Artery Aneurysms on the Ventricular Wall by Early Surgical Revascularization in Moyamoya Disease: Report of Two Cases and Review of the Literature.

BACKGROUND: Collateral artery aneurysms are a source of intracranial hemorrhage in moyamoya disease. Several reports have shown that surgical revascularization leads to the obliteration of collateral artery aneurysms. However, its effect on the prevention of rebleeding has not been established, and the optimal timing of the operation remains unclear. The purpose of the present study is to evaluate the effects of surgical revascularization and to investigate the optimal operation timing in patients with moyamoya disease who have ruptured collateral artery aneurysms on the ventricular wall. CASE DESCRIPTION: Two patients with moyamoya disease who presented with intraventricular hemorrhage caused by rupture of collateral artery aneurysms on the wall of the lateral ventricle are presented here. In both cases, the aneurysms reruptured approximately 1 month after the initial hemorrhage. Both patients successfully underwent superficial temporal artery-middle cerebral artery anastomosis combined with indirect bypass in the subacute stage. The aneurysms decreased with the development of collateral circulation through the direct bypasses, and rebleeding did not occur after the surgery. CONCLUSIONS: Because ruptured collateral artery aneurysms on the wall of the lateral ventricle in moyamoya disease are prone to rerupture within 1 month, surgical revascularization may be recommended as soon as the patients are stable and able to withstand the operation.

Sinus Pericranii with Dominant Venous Outflow in the Superior Eyelid.

Sinus pericranii (SP) located in the superior eyelid is an unusual clinical presentation. Here, we report a case of 72-year-old woman with an unruptured cerebral aneurysm presented with an SP located in the left superior eyelid. The SP was found to have a dominant venous outflow from the bilateral frontal region with an arterialized blood flow pattern on color Doppler ultrasonography (CDUS). During the aneurysmal surgery, intraoperative monitoring of the dominant venous outflow with CDUS was useful for the prevention of venous outflow obstruction. Physicians should carefully consider intracranial vascular anomalies in the differential diagnosis of vascular lesions of the superior eyelid.

Contribution of anterior cingulate cortex and descending pain inhibitory system to analgesic effect of lemon odor in mice.

BACKGROUND: Affections are thought to regulate pain perception through the descending pain inhibitory system in the central nervous system. In this study, we examined in mice the affective change by inhalation of the lemon oil, which is well used for aromatherapy, and the effect of lemon odor on pain sensation. We also examined the anterior cingulate cortex (ACC) and descending pain inhibitory system to such regulation of pain. RESULTS: In the elevated plus maze, the time spent in the open arms was increased by inhalation of lemon oil. The pain behavior induced by injection of formalin into the hind paw was decreased. By inhalation of lemon oil, the number of c-Fos expression by formalin injection was significantly increased in the ACC, periaqueductal grey (PAG), nucleu raphe magnus (NRM) and locus ceruleus, and decreased in the spinal dorsal horn (SDH). The destruction of the ACC with ibotenic acid led to prevent the decrease of formalin-evoked nocifensive behavior in mice exposed to lemon oil. In these mice, the change of formalin-induced c-Fos expression in the ACC, lateral PAG, NRM and SDH by lemon odor was also prevented. Antagonize of dopamine D1 receptor in the ACC prevented to the analgesic effect of lemon oil. CONCLUSIONS: These results suggest that the analgesic effect of lemon oil is induced by dopamine-related activation of ACC and the descending pain inhibitory system.

Production and characterization of an active single-chain variable fragment antibody recognizing CD25.

The alpha subunit of the interleukin-2 receptor (IL-2Ralpha, CD25) is a potential target in therapeutic approaches for hematolopoietic malignancies expressing CD25 on their cell surface, such as adult T cell leukemia/lymphomas. Recent reports have demonstrated that depletion of CD4+CD25+ regulatory T cells with anti-CD25 antibodies may enhance host tumor immunity. We previously raised a mouse monoclonal antibody (mAb), Ta60b mAb (IgG1kappa), specifically recognizing CD25, and an attempt was made here to produce a single chain Fv fragment (scFv) from this mAb as an initial step to development of scFv-based therapeutics. cDNA fragments encoding for the variable regions of the light and heavy chains of the Ta60b mAb were thus isolated by polymerase chain reaction-mediated cloning, and, an expression vector constructed to express Ta60b scFv fused with the maltose binding protein (MBP) in the periplasm of Escherichia coli. The soluble form of MBP-Ta60b fused scFv could be extracted and affinity-purified with an amylose/agarose column, allowing its immunoreactivity to be analyzed by enzyme-linked immunosorbent assay (ELISA), mixed hemadsorption assay, and fluorescence activated cell sorting. In addition, binding activity was studied by competitive ELISA and surface plasmon resonance. The results showed that Ta60b scFv obtained from periplasm retains good reactivity, although its KD value was 4-fold lower than that of the whole Ta60b antibody, suggesting possible clinical use for treatment of patients with CD25-expressing tumors and also for enhancing anti-tumor immunity.