Suspected Metallic Embolism following Endovascular Treatment of Intracranial Aneurysms.

We describe a case series of suspected metallic embolism after coil embolization for intracranial aneurysms. Between January 2012 and December 2014, 110 intracranial aneurysms had been treated by coil embolization in our institution. In 6 cases, the postprocedural MR imaging revealed abnormal spotty lesions not detected on the preprocedural MR imaging. The lesions were also undetectable on the postprocedural CT scan. They were demonstrated as low-intensity spots on T1WI, T2WI, DWI, and T2*-weighted imaging. On DWI, they were accompanied by bright "halo," and on T2*-weighted imaging, they showed a "blooming" effect. In 3 of the 6 cases, follow-up MR imaging was available and all the lesions remained and demonstrated no signal changes. Although histologic examination had not been performed, these neuroradiologic findings strongly supported the lesions being from metallic fragments. No specific responsible device was detected after reviewing all the devices used for the neuroendovascular treatment in the 6 cases.

Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study.

BACKGROUND: Chronic rhinosinusitis (CRS) can be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more intense eosinophilic infiltration and the presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS (ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS. METHODS: This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated patients with CRS treated with endoscopic sinus surgery (ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS. RESULTS: We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti-inflammatory drugs intolerance were associated significantly with recurrence. CONCLUSION: We subdivided CRSwNP in non-ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy.

Diffusion-weighted MR imaging in carotid angioplasty and stenting with protection by the reversed carotid arterial flow.

BACKGROUND AND PURPOSE: Distal embolism during carotid angioplasty with stent (CAS) can be protected by a flow-reversal device. Diffusion-weighted MR imaging was used to evaluate this protective procedure and perform a comparison with the control. METHODS: Cases of CAS with protection procedures were included in this study. Sixty-five men (68 procedures) and 5 women (5 procedures), with an average age of 68.8 years, having severe carotid stenosis were treated in our department between 2002 and 2004. Eleven cases were treated with the Parodi Anti-Emboli System, with which the internal carotid blood flow is reversed by simultaneous occlusion of the proximal common carotid artery and external carotid artery. Diffusion-weighted MR imaging was performed within 1-3 days after CAS. As controls, data from diffusion-weighted MR imaging in 26 patients who had diagnostic angiography were included. RESULTS: Diffusion-weighted MR imaging in diagnostic angiography showed 11.5% appearance of ischemic spots after procedures. In the Parodi Anti-Emboli System, this value was 18.2%. In the CAS group, ischemic lesions appeared only in the hemisphere ipsilateral to carotid stenosis. There were no ischemic lesions in the opposite carotid or vertebrobasilar territory. The appearance rate of new ischemic spots was not significantly different between the control group and the group of CAS with Parodi Anti-Emboli System (chi2 test, P = .6227, Fisher exact method). CONCLUSIONS: Protection results obtained with the Parodi system were excellent and comparable with conventional angiography.

[Stenting for proximal subclavian and brachiocephalic artery occlusion--preliminary results].

The authors report the initial results, between January 1998 and February 2001, of stenting utilizing the brachial approach in seven patients for total occlusions at the following locations: two right subclavian, one brachiocephalic, and five left subclavian arteries. All lesions were associated with subclavian steal syndrome. Indications for the treatment included ischemic symptoms in the affected arm (seven patients), and vertebrobasilar insufficiency (five patients). A total of eight stents were implanted in six occluded arteries, resulting in a 75% procedural success rate. Procedural complications encountered were two subintimal dissections by a 0.035-inch guide wire during recanalization, and one stent dislodgement with migration. There was no stroke, presumably because of the previously reported preventive effect of delayed reversal of a stealing vertebral artery. Follow-up over a mean duration of 11 months revealed no sign or symptom of recurrence in cases with initial technical success. The results of the current study, with a literature survey, indicated that percutaneous transluminal angioplasty with primary stent deployment in an occluded prevertebral segment of the subclavian or the brachiocephalic artery should be considered as an available choice for treatment. Further points, such as some remaining technical and clinical problems, will require more experience and consideration.

Os odontoideum associated with hypertrophic ossiculum terminale. Case report.

The authors report on the case of a 20-year-old man who presented with a transient tetraparesis. Neuroimaging studies demonstrated atlantoaxial dislocation and ventral compression of the rostral spinal cord caused by a quite rare association of os odontoideum and hypertrophic ossiculum terminale. The patient underwent removal of two free ossicula via a transoral approach and posterior fusion in which an autogenous bone graft was placed. The majority of cases of os odontoideum are believed to be an acquired form; however, controversy with regard to the congenital causes of os odontoideum remains. One hypothesis is that os odontoideum results from the failure of fusion and the hypertrophy of the proatlas, although considerable confusion surrounds this hypothesis because definitive classification of os odontoideum-to differentiate between similar anomalies-has not been established. This rare coincidence in the current case supports the belief that os odontoideum has a different embryological origin from ossiculum terminale, which is thought to be a proatlantal remnant.

Vascular reconstruction of a vertebral artery loop causing cervical radiculopathy and vertebrobasilar insufficiency. Case report.

The authors present the case of a 62-year-old man with a 4-month history of progressive left-sided C-5 radiculopathy and dizziness. Neuroimaging studies revealed a looped vertebral artery (VA) that had migrated into the widened left C4-5 intervertebral foramen. The patient underwent vascular reconstruction of the VA loop, in which there was minimal manipulation of the C-5 nerve root, via a left-sided anterolateral approach after a balloon occlusion test. Postoperatively the patient's symptoms improved immediately, and there were no signs of recurrence within the 2-year follow-up period. This excellent outcome supports the belief that a proper surgical reconstruction of the compressive, tortuous VA should be the therapeutic option of choice, which carries a lower risk of the nerve root injury and improves the hemodynamics in the posterior circulation.

[Stenting for the occlusive carotid and subclavian arteries in Takayasu arteritis].

The authors report the initial results of stenting in four patients of Takayasu arteritis for 11 occlusive carotid and subclavian arteries between January 1999 and December 2000. The lesions included stenoses of two right subclavian, three right common carotid, two left common carotid, and two left subclavian arteries, and total occlusion of two subclavian arteries. A total of 14 stents were implanted in 10 arterial lesions, resulting in a 91% procedural success rate. One failure was due to inability to cross the total occlusion of the subclavian artery. Procedural complications and problems were pain during balloon angioplasty in three patients, vaso-vagal reflex in two, carotid artery perforation associated with transient horseness in one, and stent migration in one. There was no permanent morbidity. Follow-up over a mean duration of 12 months revealed one symptomatic recurrence of left subclavian stenosis, followed by a successful re-dilatation. The results of the current study indicated that primary stenting is an excellent therapeutic option for the occlusive carotid and subclavian arteries in Takayasu arteritis. A long-term follow-up is required to determine the response or behavior of stented segments of the affected arteries.

Restenosis after stent placement for ostial stenosis of vertebral artery.

SUMMARY: The purpose of this study was to evaluate our initial procedural success rate and angiographical outcome of stent placement for vertebral artery (VA) stenosis at the intermediate followup period (11.3 +/- 7.3 months). Stent placement was successfully performed in 20 procedures (19 patients), resulting in a marked reduction of stenosis from 78.7 +/- 12.6 % before to 8.7% +/- 10.6 after stenting. Follow-up angiography, performed after an interval of 11.3 +/- 7.3 months, revealed restenosis greater than 50% in a total of 6 procedures (40%) out of 15. Although PTA with stent placement for stenosis affecting VA origin provided excellent initial success, restenosis occurred at a significant rate even during the intermediate follow-up period.

SDF-1 has costimulatory effects on human T cells: possible involvement of MAPK (ERK2) activation.

Stromal cell-derived factor-1 (SDF-1) is an efficacious chemoattractant for lymphocytes, monocytes and hematopoietic progenitor cells. In the present study, we examined whether SDF-1 has growth promoting activity on human peripheral T cells and analyzed the possible underlying signal transduction pathways. SDF-1 augmented the proliferation of anti-CD3- or PHA-stimulated normal human PBMC in a dose-dependent manner but not that of resting PBMC. It was noted that SDF-1 alone could induce a significant proliferation of PHA-preactivated T cells. Anti-SDF-1 sera could inhibit the augmentation of T-cell proliferation in each experiment. Furthermore, Western blot analysis revealed that mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 2 (ERK2), but not c-Jun N-terminal kinase (JNK) was activated by SDF-1. Considering that costimulatory signals have been reported to involve ERK2 activation, these results indicate that SDF-1 has costimulatory effects on T cells that are possibly mediated by ERK2 activation and may play a role in not only migration but also the potentiation or maintenance of T cells.

Targeted disruption of the plasmodium berghei CTRP gene reveals its essential role in malaria infection of the vector mosquito.

CTRP (circumsporozoite protein and thrombospondin-related adhesive protein [TRAP]-related protein) of the rodent malaria parasite Plasmodium berghei (PbCTRP) makes up a protein family together with other apicomplexan proteins that are specifically expressed in the host-invasive stage 1. PbCTRP is produced in the mosquito-invasive, or ookinete, stage and is a protein candidate for a role in ookinete adhesion and invasion of the mosquito midgut epithelium. To demonstrate involvement of PbCTRP in the infection of the vector, we performed targeting disruption experiments with this gene. PbCTRP disruptants showed normal exflagellation rates and development into ookinetes. However, no oocyst formation was observed in the midgut after ingestion of these parasites, suggesting complete loss of their invasion ability. On the other hand, when ingested together with wild-type parasites, disruptants were able to infect mosquitoes, indicating that the PbCTRP gene of the wild-type parasite rescued infectivity of disruptants when they heterologously mated in the mosquito midgut lumen. Our results show that PbCTRP plays a crucial role in malaria infection of the mosquito midgut and suggest that similar molecular mechanisms are used by malaria parasites to invade cells in the insect vector and the mammalian host.

Small amino acid changes in the V3 loop of human immunodeficiency virus type 2 determines the coreceptor usage for CXCR4 and CCR5.

HIV-2 GH-1 is a molecular clone derived from an AIDS patient from Ghana. In contrast to the prototypic molecular clone ROD, GH-1 exhibits a narrow range of target cell specificity. By an infectious assay using HeLa-CD4 cells stably transfected with an HIV-1 LTR-beta-galactosidase reporter gene and transiently expressing various cloned chemokine receptors, we have examined the coreceptor usage of GH-1. In contrast to ROD, which uses principally CXCR4, GH-1 was found to use mainly if not exclusively CCR5 but not CXCR4. The distinct coreceptor usage of these two molecular clones allowed us to further map the region of gp120 that is important for the coreceptor specificity. By constructing a series of chimeric viruses between GH-1 and ROD, we have demonstrated that the C-terminal half of the V3 loop region of gp120 determines the differential coreceptor usage between GH-1 and ROD, and only a few amino acid differences in this region appear to be able to shift the specificity between CCR5 and CXCR4. Notably, the shift in the coreceptor usage from CCR5 to CXCR4 is associated with an increase in the net positive charge in the V3 region.

Relapsing polychondritis diagnosed by Tc-99m MDP bone scintigraphy.

PURPOSE: Relapsing polychondritis is a generalized recurring disease of cartilage that involves joints, trachea, bronchi, laryngeal cartilages, costal cartilages, and cartilages of the ear and nose. It is associated with autoimmune diseases, including Hashimoto disease in some cases. METHODS: The authors evaluated a 29-year-old man with relapsing polychondritis who had symptoms and signs of a common cold for 2 months and anterior chest pain near the sternum for 1 month. RESULTS: After the diagnosis, the authors found that the patient had a history of thyroid therapy for hyperthyroidism 15 years before. Tc-99m MDP bone scintigraphy performed to evaluate anterior chest pain showed diffusely increased accumulation of radioactivity in all costocartilages and sternoclavicular joints. Based on that information, relapsing polychondritis was diagnosed. Ga-67 citrate scintigraphy was preformed to determine the optimum biopsy site of the cartilage. The diagnosis was histologically supported by the results of the open biopsy. CONCLUSIONS: In this case, Tc-99m MDP bone scintigraphy was useful for diagnosing relapsing polychondritis, and Ga-67 citrate scintigraphy was helpful in determining the biopsy site.

T-tropic human immunodeficiency virus type 1 (HIV-1)-derived V3 loop peptides directly bind to CXCR-4 and inhibit T-tropic HIV-1 infection.

Certain types of chemokine receptors have been identified as coreceptors for HIV-1 infection. The process of viral entry is initiated by the interaction between an envelope protein gp120 of HIV-1, CD4, and one of the relevant coreceptors. To understand the precise mechanism of the Env-mediated fusion and entry of HIV-1, we examined whether the V3 region of gp120 of T-cell line tropic (T-tropic) virus directly interacts with the coreceptor, CXCR-4, by using five synthetic V3 peptides: two cyclized V3 peptides (V3-BH10 and V3-ELI) which correspond to the V3 regions of the T-tropic HIV-1 IIIB and HIV-1 ELI strains, respectively, a linear V3 peptide (CTR36) corresponding to that of HIV-1 IIIB strain; and cyclized V3 peptides corresponding to that of the macrophage-tropic (M-tropic) HIV-1 ADA strain (V3-ADA) or the dualtropic HIV-1 89.6 strain (V3-89. 6). FACScan analysis with a CXCR-4(+) human B-cell line, JY, showed that V3-BH10, V3-ELI, and V3-89.6 but not CTR36 or V3-ADA blocked the binding of IVR7, an anti-CXCR-4 monoclonal antibody (MAb), to CXCR-4 with different magnitudes in a dose-dependent manner, while none of the V3 peptides influenced binding of an anti-CD19 MAb at all. Next, the effects of the V3 peptides on SDF-1beta-induced transient increases in intracellular Ca2+ were investigated. Three V3 peptides (V3-BH10, V3-ELI, and V3-89.6) prevented Ca2+ mobilization. Furthermore, the three peptides inhibited infection by T-tropic HIV-1 in a dose-dependent manner as revealed by an MTT assay and a reverse transcriptase assay, while the other peptides had no effects. These results present direct evidence that the V3 loop of gp120 of T-tropic HIV-1 can interact with its coreceptor CXCR-4 independently of the V1/V2 regions of gp120 or cellular CD4.

Substrate specificity of human monoamine (M)-form phenol sulfotransferase: preparation and analysis of Dopa 3-O-sulfate and Dopa 4-O-sulfate.

Upon two-dimensional thin-layer separation, the sulfated L-3, 4-dihydroxyphenylalanine (L-DopaS) generated enzymatically was found to co-migrate with only one of the two ninhydrin-stained spots corresponding to the two sulfated forms (3-O-sulfate and 4-O-sulfate) of synthetic L-DopaS. To clarify precisely the identity of the enzymatically generated L-DopaS, the two sulfated forms of synthetic L-DopaS were separated and purified using high performance liquid chromatography. Purified L-Dopa 3-O-sulfate and L-Dopa 4-O-sulfate were identified by 1H-nuclear magnetic resonance (NMR) spectrometry and used as standards in the analysis of the L-DopaS generated during metabolic labeling of HepG2 human hepatoma cells or enzymatic assay using recombinant human monoamine (M)-form phenol sulfotransferase. The results obtained demonstrated unequivocally the generation of L-Dopa 3-O-sulfate, indicating the specificity of the M-form phenol sulfotransferase being for the meta-hydroxyl group of L-Dopa.

Detection and delineation of CXCR-4 (fusin) as an entry and fusion cofactor for T-tropic [correction of T cell-tropic] HIV-1 by three different monoclonal antibodies.

A chemokine receptor, CXCR-4, has been identified as an entry cofactor for T cell line-tropic (T-tropic) HIV-1. To detect expression of CXCR-4 at the single cell level and dissect postbinding events of HIV-1 infection, we generated three mAbs against human CXCR-4. These mAbs inhibited SDF-1-induced intracellular Ca2+ mobilization, and one of the mAbs immunoprecipitated a specific 47-kDa component from CXCR-4+ cells. Flow cytometric analysis showed that most human cell lines examined expressed CXCR-4. A fraction of normal PBMC expressed CXCR-4, but neutrophils were negative. Two-color analysis revealed that the majority of T cells, virtually all B cells, and all monocytes expressed CXCR-4, while it was only weakly present on NK cells. Thus, expression of CXCR-4 is not ubiquitous but cell type specific in hemopoietic cells. The three mAbs were shown to suppress cell fusion mediated by envelope proteins of a T-tropic NL432 virus but not by those of an M-tropic JRCSF virus Likewise, they suppressed infection of NL432 but not that of an M-tropic NL162 virus. In both cases it was noted that the suppressive activity varied considerably among the mAbs. These data confirmed that CXCR-4 is directly involved in env-mediated entry and fusion of T-tropic HIV-1 and suggest that the epitopes on CXCR-4 recognized by the three mAbs may have different roles in interaction with the envelope proteins of T-tropic HIV-1.

Thoracic spinal angiomyolipoma with extracanal extension to the thoracic cavity. A case report.

STUDY DESIGN: Case report and review of the literature. OBJECTIVE: To describe a 72-year-old man with thoracic spinal angiomyolipoma in the ventral aspect of the epidural space and extracanal extension to the posterior mediastinum, to discuss the clinical and radiologic features and unique biologic behavior of this entity, and to review of the literature on angiolipoma and angiomyolipoma. SUMMARY OF BACKGROUND DATA: Spinal angiolipoma and angiomyolipoma are rare tumors, which are localized almost exclusively in the dorsal epidural space of the thoracic spine. Most reported cases have no tendency to involve the surrounding tissue. METHODS: The authors describe the radiologic, surgical, and pathologic findings of this patient and review the findings from other reported cases. RESULTS: Anterior decompression was performed using a right transthoracic incision, and the neurologic symptoms improved immediately. There were no signs of recurrence of the tumor or neurologic deficit within a 2-year follow-up period. CONCLUSION: Results of a literature survey of these tumors support management by prompt and radical surgical intervention for long-term cure, even in cases in which the infiltrating nature is recognized.

V3 loop of human immunodeficiency virus type 1 reduces cyclin E expression and induces G1 arrest in interleukin 2-dependent T cells.

We previously described that V3 loop derived from the HTLV-III BH10 clone V3-BH10 markedly suppressed IL-2-driven T cell proliferation and produced G1 arrest of the cells. Here, we tested the effect of V3-BH10 on the molecules that are involved in transition from the G1 to S phase of the cell cycle. The effect of V3-BH10 on the IL-2-induced expression of G1 cyclins, Cdk inhibitors, and phosphorylation of retinoblastoma protein (pRb) was tested by immunoblotting, using the IL-2-dependent CD4-positive cell line Kit 225. Furthermore, IL-2-dependent kinase activity of the cyclin E-Cdk2 complex was investigated with histone H1 as a substrate. V3-BH10 reduced the IL-2-dependent expression of cyclin E, but not that of cyclin D and Cdk inhibitors such as p21 and p27. As the result of reduction of cyclin E, histone H1 kinase activity of the cyclin E-Cdk2 complex was markedly reduced even in the presence of rIL-2, followed by incomplete phosphorylation of pRb. The reduction in hyperphosphorylation of pRb by V3-BH10 led to G1 arrest of the cell cycle. Thus, V3-BH10 induced G1 arrest in IL-2-dependent cell cycle progression by reducing cyclin E expression, which may be one of the mechanisms underlying the dysfunction of T cells in HIV-1-infected people.

The upregulation of p27Kip1 by rapamycin results in G1 arrest in exponentially growing T-cell lines.

An immunosuppressant Rapamycin (Rap) has been reported to cause G1 arrest by inhibiting p70 S6 kinase and G1 cyclin/cdks kinase activities when added to quiescent cells with mitogens. However, antiproliferative effects of Rap on exponentially growing cells have been poorly investigated. We examined the intracellular events after the treatment of Rap in exponentially growing T cells and found that Rap upregulated a cdks inhibitor, p27Kip1 at both mRNA and protein levels in Rap-sensitive cells. Antiproliferative effect of Rap was mainly ascribed to the inhibition of cyclin E/cdk2 kinase activity through the formation of cyclin E/cdk2-p27Kip1 complex rather than inhibition of p70 S6 kinase activity. Furthermore, we showed that Rap-sensitive cells with elevated p27Kip1 expression lost sensitivity to Rap when antisense p27Kip1 was introduced, which indicates that the basal level of p27Kip1 is one of the limiting factors that determine the sensitivity to Rap in already cycling cells. These data suggest the presence of a putative threshold level of p27Kip1 at late G1 phase in already cycling cells. Rap may cause G1 arrest by upregulating the amount of p27Kip1 beyond the threshold in some Rap-sensitive cells that are exponentially growing.

An unusual clinical course after mole evacuation: a case report.

A 27-year-old woman evacuated a hydatidiform mole at 11 weeks of gestation. Her serum human chorionic gonadotropin (hCG) levels declined progressively but reached a plateau of 2-3 mIU/ml thereafter. The patient was treated with two courses of methotrexate, which did not affect her hCG levels. She refused further chemotherapy and, for more than one year, she was managed expectantly until a significant rise in her hCG titer. Fortunately, an unexpected pregnancy and subsequent missed abortion led to a spontaneous regression of her hCG levels.

V3 loop of human immunodeficiency virus type 1 suppresses interleukin 2-induced T cell growth.

We tested the effect of three linear or two loop peptides derived from the V3 region of the HTLV-III BH10 clone or the SF2 strain of human immunodeficiency virus type 1 on IL-2-driven T cell proliferation. V3-BH10, which consists of 42 amino acids and has a loop structure, suppressed IL-2-driven proliferation of all IL-2-dependent cells [Kit225, ED-40515(+), KT-3, 7-day PHA-blasts, and fresh peripheral blood mononuclear cells] tested, whereas it did not suppress the cell growth of IL-2-independent cell lines (Hut102, Molt-4, and Jurkat). This suppressive effect was also seen in IL-2-driven cell growth of CD8-positive lymphocytes purified from 7-day PHA-blasts, indicating that CD4 molecules were not required for the suppression. The treatment with anti-V3 loop monoclonal antibody (902 antibody) completely abolished the suppressive effect of V3-BH10. In addition, V3-BH10 generated the arrest of Kit225 cells and also purified CD8-positive lymphocytes in G1 phase in the presence of IL-2. Neither chromatin condensation nor DNA fragmentation was detected in Kit225 cells cultured with V3-BH10 and IL-2. V3-BH10 neither blocked radiolabeled IL-2 binding to IL-2 receptors nor affected tyrosyl phosphorylation of several cellular proteins (p120, p98, p96, p54, and p38), which is immediately induced by IL-2 stimulation. However, V3-BH10 enhanced IL-2-induced mRNA expression of c-fos but not c-myc or junB. Thus, the binding of V3 loop of gp120 to the cell surface molecule(s) appears to affect intracellular IL-2 signaling, which leads to the suppression of IL-2-induced T cell growth.