c Shiga toxin (Stx), a major virulence factor of enterohemorrhagic Escherichia coli (EHEC), can be classified into two subgroups, Stx1 and Stx2, each consisting of various closely related subtypes. Stx2 subtypes Stx2a and Stx2d are highly virulent and linked with serious human disorders, such as acute encephalopathy and hemolytic-uremic syndrome. Through affinity-based screening of a tetravalent peptide library, we previously developed peptide neutralizers of Stx2a in which the structure was optimized to bind to the B-subunit pentamer. In this study, we identified Stx2d-selective neutralizers by targeting Asn16 of the B subunit, an amino acid unique to Stx2d that plays an essential role in receptor binding. We synthesized a series of tetravalent peptides on a cellulose membrane in which the core structure was exactly the same as that of peptides in the tetravalent library. A total of nine candidate motifs were selected to synthesize tetravalent forms of the peptides by screening two series of the tetravalent peptides. Five of the tetravalent peptides effectively inhibited the cytotoxicity of Stx2a and Stx2d, and notably, two of the peptides selectively inhibited Stx2d. These two tetravalent peptides bound to the Stx2d B subunit with high affinity dependent on Asn16. The mechanism of binding to the Stx2d B subunit differed from that of binding to Stx2a in that the peptides covered a relatively wide region of the receptor-binding surface. Thus, this highly optimized screening technique enables the development of subtypeselective neutralizers, which may lead to more sophisticated treatments of infections by Stx-producing EHEC. Shiga toxin (Stx) is a major virulence factor of enterohemorrhagic Escherichia coli (EHEC), which causes bloody diarrhea, hemorrhagic colitis, and sometimes life-threatening systemic complications such as acute encephalopathy and hemolytic-uremic syndrome (HUS) (1-6). To date, numerous EHEC strains that produce various Stx subtypes have been reported (7,8). These Stxs can be classified into two subgroups, Stx1 and Stx2, each consisting of various closely related subtypes, such as Stx1a,. Stx2a (10, 11) and Stx2d, which is activated by elastase derived from the intestinal mucosa (12-14), are highly virulent and have been linked with HUS, the most serious sequela of EHEC infection. The pathophysiologic importance of these subtypes was also confirmed by the finding that Stx2a and Stx2d are highly toxic when injected into mice (15, 16) or primates (17-19). Therefore, Stx neutralizers, particularly those customized to specifically neutralize Stx2a and Stx2d, would be highly valuable therapeutic agents for treating infections caused by various EHEC strains.Stx molecules consist of a catalytic A subunit, which has RNA N-glycosidase activity and inhibits eukaryotic protein synthesis (20,21), and a B-subunit pentamer. The B-subunit pentamer is responsible for high-affinity binding to the functional cell surface receptor Gb3 (Gal␣[1-4]-Gal[1-4]-Glc-ceramide) (4,22,23) or Gb4 (GalNAc[1-3]-Gal␣[1-4]-G...
Background: Large and giant aneurysms are known to involve intra-aneurysmal thrombosis and present a poor prognosis because of compression of the surrounding brain tissue with enlargement of the aneurysm. These aneurysms are difficult to cure by endovascular treatment due to involvement of the vasa vasorum in their pathology. We report this technical note to describe stent-assisted jam-packed coil embolization for the treatment of a giant thrombosed aneurysm. Case Description: A 62-year-old man presented with right homonymous hemianopsia, and magnetic resonance imaging (MRI) showed a giant thrombosed aneurysm with poor wall contrast enhancement, which indicates little involvement of the vasa vasorum, at the terminal part of the left internal carotid artery. To block blood flow into the aneurysmal dome, stent-assisted “jam-packed” coil embolization was performed. For this, a braided stent was shortened to enhance metal coverage ratio and tight aneurysmal coil packing was performed using a hydrogel coil. Our technique resulted in complete obliteration of the aneurysm, and MRI performed 1 year later showed remarkable shrinkage of the aneurysm dome. Conclusion: Stent-assisted jam-packed coil embolization technique might be effective in shrinking the dome of giant thrombosed aneurysms with poor wall contrast enhancement.
Background: this study aimed to evaluate the prognostic factors associated with long-term survival after linear accelerator (linac)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for brain metastasis (BM). Methods: This single-center retrospective study included 226 consecutive patients with BM who were treated with linac-based SRS or fSRT with a micro-multileaf collimator between January 2011 and December 2018. Long-term survival (LTS) was defined as survival for more than 2 years after SRS/fSRT. Results: The tumors originated from the lung (n = 189, 83.6%), breast (n = 11, 4.9%), colon (n = 9, 4.0%), stomach (n = 4, 1.8%), kidney (n = 3, 1.3%), esophagus (n = 3, 1.3%), and other regions (n = 7, 3.1%). The median pretreatment Karnofsky performance scale (KPS) score was 90 (range: 40–100). The median follow-up time was 13 (range: 0–120) months. Out of the 226 patients, 72 (31.8%) were categorized in the LTS group. The median survival time was 43 months and 13 months in the LTS group and in the entire cohort, respectively. The 3-year, 4-year, and 5-year survival rate in the LTS group was 59.1%, 49.6%, and 40.7%, respectively. Multivariate regression logistic analysis showed that female sex, a pre-treatment KPS score ≥ 80, and the absence of extracranial metastasis were associated with long-term survival. Conclusions: female sex, a favorable pre-treatment KPS score, and the absence of extracranial metastasis were associated with long-term survival in the current cohort of patients with BM.
Purpose: To evaluate the prognostic factors associated with long-term survival after linear accelerator (linac)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for brain metastasis (BM). Methods: This single-center retrospective study included 226 consecutive patients with BM who were treated with linac-based SRS or fSRT with a micro-multileaf collimator between January 2011 and December 2018. Long-term survival (LTS) was defined as survival for more than 2 years after SRS/fSRT. The tumors originated from the lung (n =189, 83.6%), breast (n = 11, 4.9%), colon (n = 9, 4.0%), stomach (n = 4, 1.8%), kidney (n = 3, 1.3%), esophagus (n = 3, 1.3%), and other regions (n = 7, 3.1%). Results: The median pretreatment Karnofsky performance scale (KPS) score was 90 (range: 40–100). The median follow-up time was 13 (range: 0–120) months. Out of the 226 patients, 72 (31.8%) were categorized in the LTS group. The median survival time was 43 months and 13 months in the LTS group and in the entire cohort, respectively. The 3-year, 4-year, and 5-year survival rate in the LTS group was 59.1%, 49.6%, and 40.7%, respectively. Multivariate regression logistic analysis showed that female sex, a pre-treatment KPS score ≥80, and the absence of extracranial metastasis were associated with long-term survival. Conclusions: Female sex, a favorable pre-treatment KPS score, and the absence of extracranial metastasis were associated with long-term survival in the current cohort of patients with BM.
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