Tumefactive eosinophil-rich non-granulomatous small vessel vasculitis in the cerebrum in a patient with idiopathic hypereosinophilic syndrome.

The definite diagnosis of central nervous system vasculitis requires pathological verification by biopsy or surgical resection of the lesion, which may not always be feasible. A 74-year-old woman with a history of allergic rhinitis, but not asthma, presented with slowly progressive left hemiparesis. Magnetic resonance imaging of the head revealed a heterogeneously enhancing mass involving the right internal capsule and corona radiata. Histological examination of the resected specimen revealed eosinophil-rich non-granulomatous small vessel vasculitis with no neutrophil infiltration or foci of microbial infection. Epstein-Barr virus in situ hybridization was negative, and polymerase chain reaction tests for both T-cell receptor gamma and immunoglobulin heavy-chain variable region genes did not show rearrangements, excluding the possibility of lymphoma and lymphoproliferative disorders. Blood hypereosinophilia and elevated erythrocyte sedimentation rate were observed; however, anti-neutrophil cytoplasmic antibodies were not detected. A biopsy of the erythema in the hips and thighs revealed perivasculitis with eosinophilic infiltration within the dermis. Chest computed tomography revealed multiple small nodules in the lungs. Her symptoms, aside from hemiparesis, disappeared after corticosteroid administration. The clinicopathological features were similar to eosinophilic granulomatosis with polyangiitis but did not meet its current classification criteria and definition. This patient is the first reported case of idiopathic eosinophilic vasculitis or idiopathic hypereosinophilic syndrome-associated vasculitis affecting the small vessels in the brain. Further clinicopathological studies enrolling similar cases are necessary to establish the disease concept and unravel the underlying pathogenesis.

A dedifferentiated intracranial solitary fibrous tumor with osteosarcoma components: rapid tumor progression and lethal clinical course.

Solitary fibrous tumor/hemangiopericytoma is a mesenchymal tumor that originates from a common NAB2-STAT6 fusion gene and is known to very rarely demonstrate dedifferentiation in the pattern of local recurrence or distant metastasis. Here we describe for the first time a rare case of intracranial dedifferentiated solitary fibrous tumor/hemangiopericytoma with osteosarcoma components that developed in an 84-year-old man after frequent gamma knife radiosurgery over a 14-year period. We performed tumor-debulking and gamma knife radiosurgery, but unfortunately the patient died shortly after the development of dedifferentiation. There is no established treatment for dedifferentiated cases due to the rare histology and limited published data, and therefore further accumulation of histological and genetic profiles is necessary to develop novel target gene therapies.

A mutation interfering with 5-lipoxygenase domain interaction leads to increased enzyme activity.

5-Lipoxygenase (5-LOX) catalyzes two steps in conversion of arachidonic acid to proinflammatory leukotrienes. Lipoxygenases, including human 5-LOX, consist of an N-terminal C2-like ß-sandwich and a catalytic domain. We expressed the 5-LOX domains separately, these were found to interact in the yeast two-hybrid system. The 5-LOX structure suggested association between Arg(101) in the ß-sandwich and Asp(166) in the catalytic domain, due to electrostatic interaction as well as hydrogen bonds. Indeed, mutagenic replacements of these residues led to loss of two-hybrid interaction. Interestingly, when Arg(101) was mutated to Asp in intact 5-LOX, enzyme activity was increased. Thus, higher initial velocity of the reaction (vinit) and increased final amount of products were monitored for 5-LOX-R101D, at several different assay conditions. In the 5-LOX crystal structure, helix α2 and adjacent loops (including Asp(166)) of the 5-LOX catalytic domain has been proposed to form a flexible lid controlling access to the active site, and lid movement would be determined by bonding of lid residues to the C2-like ß-sandwich. The more efficient catalysis following disruption of the R101-D166 ionic association supports the concept of such a flexible lid in human 5-LOX.

Metastasis of carcinoid to the arch of the axis in a multiple endocrine neoplasia patient: a case report.

BACKGROUND CONTEXT: Carcinoid tumors eventually metastasize to the spine, and epidural spinal cord compression is a relatively frequent neurologic complication of carcinoid. However, a case of multiple endocrine neoplasia type 1 (MEN1) presenting with spinal cord compression as a result of a metastatic carcinoid tumor has not been reported previously. PURPOSE: To report an extremely rare case of MEN1 presenting with spinal cord compression by metastatic carcinoid tumor. STUDY DESIGN: Case report. METHODS: A 51-year-old man, with a past history of thymoma, insulinoma, and gastric carcinoid presented with neck pain. Neuroradiological examination revealed that a tumor around the arch of the axis compressed the spinal cord with osteoblastic changes. RESULTS: After hemilaminectomy of the axis and removal of the tumor followed by irradiation, the patient returned to his previous job. Histological examination confirmed metastatic carcinoid tumor. CONCLUSIONS: Spinal metastasis of carcinoid tumor occurred in a multiple endocrine neoplasia patient, and it is significant to note that carcinoid metastasis is one of differential diagnoses for osteoblastic lesions.

Relationship of hypotension and cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVES: Changes in systemic arterial blood pressure and the degree of cerebral vasospasm were investigated in 125 patients with aneurysmal subarachnoid hemorrhage. METHODS: Systemic arterial blood pressure was measured every 2 hours in each patient for a period of more than 2 weeks, and a fall in systemic blood pressure (FBP) was defined as a decrease of >40 mmHg of systolic blood pressure between two consecutive measurements. RESULTS: A total of 91 FBPs occurred in 52 (41.6%) of 125 patients despite specific post-operative management to prevent hypovolemia. Five (5.5%) of the 91 FBPs occurred just before the onset of symptomatic vasospasm. Symptomatic vasospasm was observed in 36 (69.2%) of 52 patients with FBP and in 32 (43.8%) of 73 patients without FBP (p<0.01, chi-squared test). A hypodense area on computed tomographic scans in association with cerebral vasospasm was observed in 25 (48.1%) of 52 patients with FBP and in 21 (28.8%) of 73 patients without FBP (p<0.05). DISCUSSION: We conclude that FBP might result from delayed cerebral vasospasm and/or brain dysfunction owing to subarachnoid hemorrhage itself.

Novel approach to calvarial bone transport using a rabbit model.

Calvarial defects sometimes require cranioplasty to protect the brain. Alloplastic materials, such as acrylic resin, hydroxyapatite ceramics, and titanium, involve various problems, such as vulnerability, infection, deformity resulting from growth, and high cost. We devised a new bone transport model in the rabbit based on the distraction osteogenesis theory of Ilizarov. Twelve Japan white rabbits with a mean body weight of 2.5 kg aged 12 weeks were used. Craniectomy (7 x 14 mm) was performed in 12 rabbits. Trapezoid bone osteotomy was performed anterior to the calvarial defect in 10 rabbits. The distraction device (Extension-plates) was fixed between the trapezoid bone island and the skull. Distraction was initiated 5 days postoperatively. The device was activated once every other day, with approximately 0.75 mm or 0.5 mm per activation. Bone distraction was continued until the rod could not be moved. The lengths of distraction were 4 mm in two cases, 5 mm in one case, 6 mm in one case, and 7 mm in two cases, with a mean of 5.5 +/- 0.56 mm. Both radiographic and histological findings showed osteogenesis by intramembranous ossification and trans-chondroid bone formation. Distraction osteogenesis has potential clinical applications in cranioplasty, especially in children because usage of autogenous bone is difficult if not impossible in most cases.

Cloning of rat p47phox and comparison with human p47phox.

A cDNA encoding rat p47phox was cloned from rat spleen cDNA library, utilizing rapid amplification of cDNA ends. The open reading frame corresponded to 389 amino acids: It contained the phagocyte oxidase homology domain, two Src homology 3 domains and a proline rich region, all of which are conserved in mammalian p47phox sequences. Rat p47phox displayed the highest degree of identity to mouse p47phox (94%). We expressed and purified rat p47phox as a glutathione S-transferase fusion protein, and found that the rat protein could replace human p47phox in a cell-free activation system for human NADPH oxidase, giving about half activity. Although rat 12-lipoxygenase interacted with human p47phox in a yeast two-hybrid system, this was not the case for rat p47phox.

C-terminus of p47(phox) is required for interaction with leukocyte type rat 12-lipoxygenase.

In yeast two-hybrid system, rat 12-lipoxygenase (12-LO) bound to complete (390 amino acids) or the N-terminus truncated form of human p47 (phox), but not to the C-terminus truncated form (residues 1-286). When glutathione S-transferase fused human p47(phox) was added to an in vitro 12-LO enzyme activity assay, formation of 12-hydroperoxyeicosatetraenoic acid was reduced significantly compared to the C-terminus truncated form. These results indicate that C-terminus of p47(phox) is important for its interaction to rat 12-LO.

Incorporation of arachidonic and linoleic acid hydroperoxides into cultured human umbilical vein endothelial cells.

The current study assessed the differential incorporation of 12-hydroperoxyeicosatetraenoic acid (12-HPETE), arachidonic acid (AA), 12-hydroxyeicosatetraenoic acid (12-HETE) and the linoleic acid (LA) oxidation products, 13-hydroxyoctadecadienoic acid (13-HODE) and 13-hydroperoxyoctadecadienoic acid (13-HPODE), into human umbilical vein endothelial cells (HUVEC). Approximately 80-90% of AA (10(-8)-10(-5)M) and 80% of LA (10(-8)-10(-5)M) were incorporated into HUVEC within 12h, while less than 50% of the hydroxy metabolites (12-HETE, 12-HPETE, 13-HODE, 13-HPODE) were incorporated into HUVEC over 48h. Further, treatment of HUVEC with either 12-HPETE or 13-HPODE (concentrations of 10(-5)M) had no effect on cell number at a 48h time point when compared with control. These results demonstrate that exogeneous hydroxy metabolites are incorporated into HUVEC to a lesser degree than were endogenous fatty acids. Further, we speculate that 12-HPETE and 13-HPODE are rapidly metabolized to substances without significant cytotoxic effects.