Role of the N-linked glycans of the prM and E envelope proteins in tick-borne encephalitis virus particle secretion

The tick-borne encephalitis (TBE) virus has two membrane glycoproteins (prM and E), which each has one N-linked glycan. Constructs that express prM and E proteins of TBE virus have been shown to produce virus-like particles (VLPs), which have surface properties that are similar to those of infectious viruses. To reveal the function of glycosylation of the TBE virus prM and E proteins in the secretion of VLPs, we expressed glycosylation-mutated prM and E proteins and compared the secretion levels and biological properties of the VLPs. In the prM protein glycosylation-deficient mutant, the level of secreted E protein was reduced to 60% of the wild-type level. On the other hand, in the E or prM-E protein glycosylation-deficient mutant, the level of secreted E protein was reduced to 10% of the wild-type level. Furthermore, the mutant which was glycosylated at positions 66 and 154 in protein E, the level of secreted E protein was four-fold higher than that of the wild-type. However, in the mutant which was glycosylated at position 66 only, E protein secretion was reduced to only 10% of the wild-type level. These data suggest that the glycan associated with the N-linked glycosylation site at position 154 in protein E plays an important role in VLP secretion.     

Interferon-alpha as a mediator of polyinosinic:polycytidylic acid-induced type 1 diabetes

A number of studies and clinical case reports have implicated interferon (IFN)-alpha as a potential mediator of type 1 diabetes pathogenesis. Administration of polyinosinic:polycytidylic acid (poly I:C), a mimic of viral double-stranded RNA, induces diabetes in C57BL/6 mice expressing the B7.1 costimulatory molecule in islets. We investigated the potential role of IFN-alpha in this disease model. The quantitative correlation between IFN-alpha levels and time to diabetes, diabetes prevention with anti-IFN-alpha antibody, and ability of IFN-alpha itself to induce diabetes are consistent with the hypothesis that poly I:C in this model acts by induction of IFN-alpha in a genetically susceptible host. Numerous recent studies highlight the importance of the innate immune system and toll receptors in determining adaptive immune responses, and we speculate that for type 1 diabetes, viral and other environmental factors may act through induction of IFNs.     

Usefulness of L-[methyl-11C] methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma

OBJECT: The authors retrospectively analyzed the data obtained in patients who had undergone L-[methyl-11C] methionine (MET)-positron emission tomography (PET) studies to clarify the relationship between MET uptake and tumor biological features and to discuss the clinical usefulness of MET-PET studies. METHODS: One hundred ninety-four patients with cerebral glioma or suspected glioma underwent PET scanning 20 minutes after injection of MET, whose uptake into the tumor was expressed as a ratio to contralateral healthy brain tissue (T/N ratio). Analyses were performed to determine how MET uptake correlated with tumor pathological features and prognosis. The T/N ratios before and after various treatments were also examined. There were significant differences in the T/N ratio among the nonneoplastic lesions, low-grade gliomas, and malignant gliomas. Furthermore, there were significant correlations between patient survival and pretreatment T/N ratios. Among patients with malignant gliomas, a significant difference in survival was observed between cases with and without postoperative tumor remnant based on elevated MET uptake. The MET uptake was heterogeneous even among the homogeneous tumor areas demonstrated on MR imaging. Malignant pathological features were detected in the areas with the highest MET uptake. The effectiveness of radiotherapy or chemotherapy was expressed as a significantly decreased T/N ratio in some of the tumor types. CONCLUSIONS: The ability of MET-PET to reflect the biological nature of gliomas makes it an excellent method for monitoring active tumor tissue, and treatments based on its findings should provide a powerful clinical protocol in the course of glioma therapy.     

Use of a modified Dumon stent for postoperative bronchopleural fistula

This report describes a case of a postoperative bronchopleural fistula successfully managed with a modified Dumon stent. Surgical interventions for the bronchopleural fistula with empyema were subsequently avoided. Dumon stent is an acceptable option for the treatment of postoperative bronchopleural fistulas.     

Paraparesis associated with ruptured anterior cerebral artery territory aneurysms

BACKGROUND: Paraparesis is a rare but characteristic manifestation of ruptured anterior communicating artery or anterior cerebral artery (ACA) aneurysms, but the pathogenesis remains unclear. This study investigated the neuroimaging and clinical features of patients with such paraparesis to evaluate possible causes. METHODS: Nine of 178 patients with ruptured anterior communicating artery or ACA aneurysms presented with paraparesis among 462 patients with subarachnoid hemorrhage (SAH) admitted between May 1996 and November 2001. Diffusion-weighted magnetic resonance (MR) imaging was performed within 48 hours of the onset of SAH in 4 of these 9 patients. The clinical course and neuroimaging studies of these 4 patients were retrospectively reviewed. RESULTS: Diffusion-weighted MR imaging revealed -intensity areas in the medial aspects of the bilateral frontal lobes, which were supplied by the ACAs and distal to the aneurysms, in all 4 patients. These high-intensity lesions had normal to subnormal values of apparent diffusion coefficient (ADC). Most of the high-intensity lesions recovered and did not result in the final lesions regardless of the ADC values, but some lesions with subnormal ADC values resulted in cerebral infarction. Paraparesis was transient and almost completely resolved in 3 patients. CONCLUSIONS: Diffusion-weighted MR imaging detected primary brain damage in the ACA territories caused by acute SAH, which was compatible with the clinical paraparesis. Primary brain damage caused by SAH may include 3 types of lesions: reversible with normal ADC value, reversible with subnormal ADC value, and irreversible with subnormal ADC value.     

Evaluation of Blood Flow by Color Doppler Sonography in Free Jejunal Interposition Grafts for Cervical Esophageal Reconstruction

The failure of the vascular anastmoses is a devastating complication in free jejunum transplantation. We used color Doppler sonography to estimate blood flow in free jejunal grafts in 21 patients who underwent radical pharyngoesophagectomy. Fast Fourier transform (FFT) analysis of blood flow, the pulsatility index (PI) as a measure of peripheral vascular resistance, and thickening of the graft wall were evaluated for predictive value. The arterial wave patterns were classified into three types based on systolic–diastolic differences and magnitude of flow. Type I was physiologic flow, type III overtly pathologic, and type II intermediate. The three patients who required vascular reanastomoses intraoperatively had a type II pattern that degenerated to type III within 15 minutes. The PI increased to 3.5 to 4.5 over 1 hour. In the one patient who required retransplantation, the wave pattern became type III by 18 hours and had disappeared by 24 hours, at which point the PI could not be measured. Jejunal thickening increased from 1.0 mm to 5.0 mm after 24 hours, even in healthy grafts. Monitoring blood flow during the 24 hours after surgery is critical. A type III wave pattern or a PI >2.5 is an indication for reexploration. Doppler sonography offers a noninvasive way to measure blood flow in jejunal grafts semiquantitatively and can predict free jejunal graft failure.     

Discrete subaortic stenosis with pressure recovery: a case report

A 54-year-old woman with subvalvular aortic stenosis was admitted to our hospital. The pressure gradient across the left ventricular outflow tract was estimated as 88 mmHg (peak) and 45 mmHg (mean) by Doppler echocardiography, but only 14 mmHg (peak to peak) and 31 mmHg (mean) by cardiac catheterization. We considered this discrepancy attributable to the presence of moderate aortic regurgitation and the pressure recovery phenomenon. Pressure recovery has clinical relevance particularly in a patient with tunnel-like stenosis, with gradual lumen re-expansion beyond the limiting orifice. Therefore, if Doppler echocardiography shows significant left ventricular outflow tract gradient, precise evaluation of the stenosis geometry is required to investigate the effect of pressure recovery.