Glycosylation of CM2 is important for efficient replication of influenza C virus

CM2 is the second membrane protein of influenza C virus and possesses a conserved motif for N-glycosylation. To investigate the role(s) of CM2 glycosylation in the virus replication, we generated rN11A, a recombinant influenza C virus lacking the glycosylation site. The rN11A virus grew less efficiently than the wild-type (WT) virus, although the biochemical characteristics of the mutant CM2 were similar to those of authentic CM2. The amount of the genome (GFP-vRNA) in the CM2-N11A-virus-like particles (VLPs) was 13% of that found in WT-VLPs. The incoming GFP-vRNA was less efficiently transported to the nucleus in CM2-N11A-VLP-infected cells than WT-VLP-infected cells, leading to the reduced reporter gene expression in CM2-N11A-VLP-infected cells. Thus the glycosylation of CM2 is required for efficient replication of influenza C virus, and the obtained findings confirmed and extended the previous observation that CM2 is involved in the genome packaging and uncoating processes.     

IL-15 exacerbates collagen-induced arthritis with an enhanced CD4+ T cell response to produce IL-17

IL-15 is thought to be involved in the pathogenesis of rheumatoid arthritis (RA). We found that IL-15 plays an important role in the development of murine collagen-induced arthritis (CIA). The incidence and severity of CIA were slightly decreased in IL-15 KO mice but were increased in IL-15 Tg mice compared with wild-type (WT) mice. The levels of type II collagen (CII)-specific IL-17 production were significantly increased in IL-15 Tg mice compared with WT mice with CIA. Expression of IL-23R was up-regulated in CD4(+) T cells in IL-15 Tg mice but down-regulated in IL-15 KO mice compared with WT mice. In correlation with the expression levels of IL-23R, IL-17 production by CD4(+) T cells in response to exogenous IL-23 was increased in IL-15 Tg mice compared with WT mice. Furthermore, exogenous IL-15 synergized with IL-23 to induce CII-specific IL-17 production by CD4(+) T cells in vitro. Taken together, these results indicate that IL-15 plays an important role in the progression of CIA through increasing antigen-specific IL-17 production by CD4(+) T cells.     

Hodgkin's reed-sternberg cell line (KM-H2) promotes a bidirectional differentiation of CD4+CD25+Foxp3+ T cells and CD4+ cytotoxic T lymphocytes from CD4+ naive T cells

A recent report revealed that a large population of Hodgkin's lymphoma-infiltrating lymphocytes (HLILs) consisted of regulatory T cells. In this study, we cocultured CD4+ naive T cells with KM-H2, which was established as a Hodgkin's Reed-Sternberg cell line, to clarify their ability to induce CD25+ Forkhead box P3+ (Foxp3+) T cells. The characteristic analyses of T cells cocultured with KM-H2 revealed the presence of CD4+CD25+ T cells. They expressed CTLA-4, glucocorticoid-induced TNFR family-related gene, and Foxp3 and could produce large amounts of IL-10. Conversely, KM-H2 also generated CD4+ CTLs, which expressed Granzyme B and T cell intracellular antigen-1 in addition to Foxp3+ T cells. They exhibit a strong cytotoxic effect against the parental KM-H2. In conclusion, KM-H2 promotes a bidirectional differentiation of CD4+ naive T cells toward Foxp3+ T cells and CD4+ CTLs. In addition to KM-H2, several cell lines that exhibit the APC function were able to generate Foxp3+ T cells and CD4+ CTLs. Conversely, the APC nonfunctioning cell lines examined did not induce both types of cells. Our findings suggest that the APC function of tumor cells is essential for the differentiation of CD4+ naive T cells into CD25+Foxp3+ T cells and CD4+ CTLs and at least partly explains the predominance of CD25+Foxp3+ T cells in HLILs and their contribution to a better prognosis. Therefore, in APC-functioning tumors, including classical Hodgkin lymphomas, which generate Foxp3+ T cells and CD4+ CTLs, these T cell repertories play a beneficial role synergistically in disease stability.     

Dysembryoplastic neuroepithelial tumor in the insular cortex. Three dimensional magnetoencephalographic localization of epileptic discharges

Abstract

A case of dysembryoplastic neuroepithelial tumor in the left insular cortex manifesting with intractable seizures is presented. The multichannel magnetoencephalography (MEG) localized equivalent current dipoles of epileptic discharges at the cerebral cortex adjacent to the tumor. The total removal of the tumor resulted in complete disappearance of seizures. This case demonstrated that multichannel MEG was useful in the three-dimensional localization of irritative zone in the concealed cortices such as inside the sylvian fissure. [Neural Res 1998; 20: 433–438]     

A peritoneal marker for optimal timing of ventriculo-peritoneal shunt revision in early childhood

Abstract

The ventriculo-peritoneal shunt placed in a neonate or infant needs revision to lengthen the peritoneal tube at certain times during childhood. The critical time for this revision is not exactly the same between individuals. Furthermore, the level of peritoneal insertion of the shunt tube is often unclear on x-ray films. To plan for and determine the optimal timing of revision, we applied a titanium clip on the peritoneal suture line in three infants as a marker of peritoneal insertion level. During the 31- to 37-month follow-up period, abdominal x-ray clearly demonstrated the peritoneal insertion level in all three patients, allowing accurate determination of the length of the intraperitoneal portion OP) of the shunt tube. The rate of shortening of the length of IP was 20 to 27% of the increase in body height (BH). This technique allows accurate determination of the length of IP and also optimal timing for revision. [Neural Res 1998; 20: 526-528]     

Comparative in vivo kinematic analysis of normal and osteoarthritic trapeziometacarpal joints

PURPOSE: Although extensive studies have been conducted on the trapeziometacarpal (TM) joint, there have been few quantitative studies on its in vivo kinematics. The purposes of this study are to quantitatively evaluate the in vivo kinematics of the TM joint with a fluoroscope and to determine the difference between normal and arthritic joints. METHODS: Fourteen healthy hands and 8 symptomatic hands with idiopathic osteoarthritis were included in this study. The healthy subjects were divided into 2 groups: a younger control group aged under 50 years (n = 7) and an older control group aged 51 years or older (n = 7). Radial and dorsal translations of the center of rotation (COR) were quantified in active abduction-adduction and active flexion-extension. In addition, volar tilt of the metacarpal facet of the TM joint was measured on the lateral view. RESULTS: The CORs in flexion-extension translated more dorsally in the patient group than those in the 2 control groups whereas the CORs in abduction-adduction did not differ significantly between the patient group and the control groups. There was no significant difference in the translation of COR between the 2 control groups in either abduction-adduction or flexion-extension. The average volar tilt in the patients with osteoarthritis increased significantly compared with those in the control groups. CONCLUSIONS: Dorsal translation of the COR in flexion-extension but not radial translation in abduction-adduction is the kinematic characteristic of the arthritic TM joint. We suggest that increased volar tilt is a predisposition to the dorsal translation of COR in the patient group.     

Iron,coronary artery calcification,and mortality in patients undergoing hemodialysis

ObjectiveA high coronary artery calcification score (CACS) may be associated with high mortality in patients undergoing hemodialysis (HD). Recently, effects of iron on vascular smooth muscle cell calcification have been described. We aimed to investigate the relationships between iron, CACS, and mortality in HD patients.MethodsWe studied 173 consecutive patients who were undergoing maintenance HD. Laboratory data and Agatston’s CACS were obtained at baseline for two groups of patients: those with CACS ≥400 (n = 109) and those with CACS <400 (n = 64). Logistic regression analyses for CACS ≥400 and Cox proportional hazard analyses for mortality were conducted.ResultsThe median (interquartile range) age and duration of dialysis of the participants were 67 (60–75) years and 73 (37–138) months, respectively. Serum iron (Fe) and transferrin saturation (TSAT) levels were significantly lower in participants with CACS ≥400 than in those with CACS <400, although the serum ferritin concentration did not differ between the groups. TSAT ≥21% was significantly associated with CACS ≥400 (odds ratio 0.46, p<0.05). TSAT ≥17%, Fe ≥63 µg/dL, and ferritin ≥200 ng/mL appear to protect against 5-year all-cause mortality in HD patients, independent of conventional risk factors of all-cause mortality (p < 0.05).ConclusionWe have identified associations between iron, CACS, and mortality in HD patients. Lower TSAT was found to be an independent predictor of CACS ≥400, and iron deficiency (low TSAT, iron, or ferritin) was a significant predictor of 5-year all-cause mortality in HD patients.     

Does lemon candy decrease salivary gland damage after radioiodine therapy for thyroid cancer?

Salivary gland dysfunction is one of the common side effects of high-dose radioiodine therapy for thyroid cancer. The purpose of this study was to determine whether an early start of sucking lemon candy decreases salivary gland injury after radioiodine therapy. METHODS: The incidence of the side effects of radioiodine therapy on the salivary glands was prospectively and longitudinally investigated in 2 groups of patients with postsurgical differentiated thyroid cancer with varying regimens for sucking lemon candy. From August 1999 to October 2000, 116 consecutive patients were asked to suck 1 or 2 lemon candies every 2-3 h in the daytime of the first 5 d after radioiodine therapy (group A). Lemon candy sucking was started within 1 h after radioiodine ingestion. From November 2000 to June 2002, 139 consecutive patients (group B) were asked to suck lemon candies in a manner similar to that of group A. In the group B, lemon candies were withheld until 24 h after the ingestion of radioiodine. Patients with salivary gland disorders, diabetes, collagen tissue diseases, or a previous history of radioiodine therapy or external irradiation to the neck were excluded. Thus, 105 patients in group A and 125 patients in group B were available for analysis. There were no statistical differences in the mean age (55.2 y vs. 58.5 y), average levels of serum free thyroxine (l-3,5,3',5'-tetraiodothyronine) (0.40 ng/dL vs. 0.47 ng/dL), and the mean dose of (131)I administered (3.96 GBq vs. 3.87 GBq) between the 2 groups. The onset of salivary side effects was monitored during hospital admission and regular follow-up on the basis of interviews with patients, a visual analog scale, and salivary gland scintigraphy using (99m)Tc-pertechnetate. When a patient showed a persistent (>4 mo) dry mouth associated with a nonfunctioning pattern on salivary gland scintigraphy, a diagnosis of xerostomia was established. RESULTS: The incidences of sialoadenitis, hypogeusia or taste loss, and dry mouth with or without repeated sialadenitis in group A versus group B were 63.8% versus 36.8% (P < 0.001), 39.0% versus 25.6% (P < 0.01), and 23.8% versus 11.2% (P < 0.005), respectively. Permanent xerostomia occurred in 15 patients in group A (14.3%) and 7 patients in group B (5.6%) (P < 0.05). In both groups, bilateral involvement of the parotid gland was the most frequently seen and was followed by bilateral involvement of the submandibular gland. CONCLUSION: An early start of sucking lemon candy may induce a significant increase in salivary gland damage. Lemon candy should not be given until 24 h after radioiodine therapy.     

Effect of resuscitative endovascular balloon occlusion of the aorta in hemodynamically unstable patients with multiple severe torso trauma: a retrospective study

Background

Although resuscitative endovascular balloon occlusion of the aorta (REBOA) may be effective in trauma management, its effect in patients with severe multiple torso trauma remains unclear.

Methods

We performed a retrospective study to evaluate trauma management with REBOA in hemodynamically unstable patients with severe multiple trauma. Of 5899 severe trauma patients admitted to our hospital between January 2011 and January 2018, we selected 107 patients with severe torso trauma (Injury Severity Score >?16) who displayed persistent hypotension [≥?2 systolic blood pressure (SBP) values ≤?90 mmHg] regardless of primary resuscitation. Patients were divided into two groups: trauma management with REBOA (n?=?15) and without REBOA (n?=?92). The primary endpoint was the effectiveness of trauma management with REBOA with respect to in-hospital mortality. Secondary endpoints included time from arrival to the start of hemostasis. Multivariable logistic regression analysis, adjusted for clinically important variables, was performed to evaluate clinical outcomes.

Results

Trauma management with REBOA was significantly associated with decreased mortality (adjusted odds ratio of survival, 7.430; 95% confidence interval, 1.081–51.062; p?=?0.041). The median time (interquartile range) from admission to initiation of hemostasis was not significantly different between the two groups [with REBOA 53.0 (40.0–80.3) min vs. without REBOA 57.0 (35.0–100.0) min ]. The time from arrival to the start of balloon occlusion was 55.7?±?34.2 min. SBP before insertion of REBOA was 48.2?±?10.5 mmHg. Total balloon occlusion time was 32.5?±?18.2 min.

Conclusions

The use of REBOA without a delay in initiating resuscitative hemostasis may improve the outcomes in patients with multiple severe torso trauma. However, optimal use may be essential for success.