Microscopic Visualization of Metabotropic Glutamate Receptors on the Surface of Living Cells Using Bifunctional Magnetic Resonance Imaging Probes

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Miniarthrotomy assisted percutaneous screw fixation for displaced medial malleolus fractures – A novel technique

Aim

To describe here a technique of miniarthrotomy assisted percutaneous screw insertion for displaced Herscovici type B and C medial malleolar fractures.

Method

Incision was made centred over the superomedial angle of the ankle mortise, about half a cm medial to tibialis anterior. Arthrotomy was done and reduction obtained. Percuntaneously, two 4 mm cancellous cannulated screws were inserted through medial malleolus.

Results and conclusion

This approach allows direct visualization of reduction, removal of entrapped soft tissue and preservation of saphenous vein and nerve.     

Treatment of non-union of humerus diaphyseal fractures: a prospective study comparing interlocking nail and locking compression plate

Background

The aim of this prospective comparative study was to compare outcomes and complications of humeral diaphyseal fracture non-unions managed with humerus interlocking nail (HIL) and locking compression plate (LCP).

Materials and methods

40 patients with non-union of humeral diaphyseal fractures were included in this study and were randomly allocated in two groups; group A had 20 cases treated with HIL and group B had 20 cases treated with LCP. Clinico-radiological assessments were done for each case up to 2-year follow-up period. Primary outcome measures (time to fracture union, union rate) and secondary outcome measures (functional outcome and complication such as infection, malunion, delayed union, implant failure, joint stiffness and iatrogenic radial nerve palsy) were compared between both the groups. Disabilities of the arm, shoulder and hand (DASH) scoring and Steward and Hundley’s scoring system were used to assess functional outcome of the fracture fixation.

Results

There was no significant difference (p = 0.12) in terms of mean fracture union time between group A (15.8 ± 4.2 weeks) and group B (17.2 ± 3.8 weeks). Group A had 95 % union rate and group B had 100 % union rate (p = 0.14). At the 2-year follow-up visit, there was no significant difference found between both the groups regarding range of motion of shoulder and elbow joint. There was no significant difference found in final functional outcomes between both the groups on comparing DASH score (p = 0.14) and Steward and Hundley’s score (p = 0.08). In terms of complications, there was insignificant difference found between both the groups.

Conclusions

This study concludes that both the implants can be used in non-union of humeral shaft fractures with good functional outcomes and acceptable rate of complications.     

Phagocytic cells internalize ZnO particles by FcγII/III-receptor pathway

The present study investigates the process of internalization for bulk ZnO particles in macrophages, and further elucidates the underlying mechanism. Since macrophages are active phagocytes and phagocytosis is a size dependent phenomenon, therefore we hypothesized that bulk ZnO may internalize into macrophages by phagocytic pathways. Interestingly, the phagocytic activity got enhanced in bulk ZnO treated macrophages. Moreover, the bulk ZnO treated macrophages internalized via FcγR-II/III, complement and scavenger–receptor pathways. To confirm the specificity of phagocytic pathway, the uptake was also analyzed in splenocytes where phagocytic (monocytes) and non-phagocytic cells (lymphocytes) are present. It was observed that no significant uptake of bulk ZnO in case of lymphocytes whereas significant uptake in monocytes. Henceforth, our quest for uptake mechanisms also revealed that severe plasma membrane extensions (pseudopodia), FcγR clustering over the surface of macrophages and activation of FcγR signaling were the key players for bulk ZnO uptake; whereas clathrin or caveolae mediated endocytic pathways contributed less. Uptake of these particles was further strengthened by the ZnO-induced activation of the Src-kinase p-Lyn, phospho-tyrosine kinases Syk (spleen tyrosine kinase), p-PLC-γ and PI3K (phosphatidylinositol 3-kinase). Our findings illustrate that the phagocytic nature of macrophages could have led to higher uptake of bulk ZnO.     

Was RA Fisher Right?

Randomized controlled trials have become the most respected scientific tool to measure the effectiveness of a medical therapy. The design, conduct and analysis of randomized controlled trials were developed by Sir Ronald A. Fisher, a mathematician in Great Britain. Fisher propounded that the process of randomization would equally distribute all the known and even unknown covariates in the two or more comparison groups, so that any difference observed could be ascribed to treatment effect. Today, we observe that in many situations, this prediction of Fisher does not stand true; hence, adaptive randomization schedules have been designed to adjust for major imbalance in important covariates. Present essay unravels some weaknesses inherent in Fisherian concept of randomized controlled trial.     

Systematic survey of discrepancy rates in an international teleradiology service

International teleradiology services (ITS) to the United States are based on the principle of deploying American board-certified radiologists across global time zones to optimally distribute the workload. While errors may be reduced by circumventing the traditional night call, there is limited evidence on the actual error rates of teleradiology groups. We have a comprehensive quality assurance (QA) process in our practice, which includes a review of discrepancies between preliminary reports and the final reports by the on-site radiologists. We analyzed the discrepancy QA data to determine the error rates. Archived QA data for 126,449 cases over a period of 1?year (2008) were analyzed for the discrepancy rate, nature of errors, and possible contributory factors. The scores ranged from 0 (no error) to 5 (clinically significant in the acute setting) based on the level of clinical significance. A novel modified Lorenz plot was used to estimate the degree of underreporting and to estimate the true error rate. An internal review of 200 cases was performed to validate the findings. Of the total, there was a total of 227 confirmed errors (0.18%, 95% CI, 0.16 to 0.20). Of these, the majority were levels 2 and 3 (minor error and error of long-term significance but not in the acute setting). Even after correction for underreporting, error rates were less than 1% for clinically significant errors. ITS is associated with very low rates of clinically significant errors. Due to limited feedback, particularly for minor errors, an internal review is important.     

Increased enzyme binding to substrate is not necessary for more efficient cellulose hydrolysis

Substrate binding is typically one of the rate-limiting steps preceding enzyme catalytic action during homogeneous reactions. However, interfacial-based enzyme catalysis on insoluble crystalline substrates, like cellulose, has additional bottlenecks of individual biopolymer chain decrystallization from the substrate interface followed by its processive depolymerization to soluble sugars. This additional decrystallization step has ramifications on the role of enzyme–substrate binding and its relationship to overall catalytic efficiency. We found that altering the crystalline structure of cellulose from its native allomorph I_β to III_I results in 40–50% lower binding partition coefficient for fungal cellulases, but surprisingly, it enhanced hydrolytic activity on the latter allomorph. We developed a comprehensive kinetic model for processive cellulases acting on insoluble substrates to explain this anomalous finding. Our model predicts that a reduction in the effective binding affinity to the substrate coupled with an increase in the decrystallization procession rate of individual cellulose chains from the substrate surface into the enzyme active site can reproduce our anomalous experimental findings.     

Intratumoral coinjection of two adenoviral vectors expressing functional interleukin-18 and inducible protein-10, respectively,synergizes to facilitate regression of established tumors

We have constructed two recombinant adenoviral vectors AdVIP-10 and AdVIL-18 expressing the functional chemokine IFN-gamma inducible protein (IP)-10 and cytokine interleukin (IL)-18, respectively. Injection of either AdVIP-10 or AdVIL-18 subcutaneously into tumor nodules derived from the J558 murine myeloma cell line delayed some tumor growth but it was not curative in all cases. Coinjection of these two vectors at the same tumor nodule not only significantly suppressed the tumor growth, but also cured established tumors in 8 of 10 (80% tumor free) mice. The latter treatment stimulated T-cell infiltration into tumors in association with tumor necrosis formation, induced a type 1 immune response and induced the activation of J558 tumor-specific cytotoxic T lymphocytes. Moreover, the antitumor activity of IP-10 and IL-18 combined gene therapy was significantly diminished in mice with depletion of either CD4(+) (50% tumor free) or CD8(+) (40% tumor free) T cells, and completely lost (0% tumor free) in T cell-deficient nude and IFN-gamma knockout mice, indicating the critical roles of T cells and IFN-gamma in this therapeutical model. Taken together, the findings of this study demonstrate that the combined use of two adenoviral vectors expressing IP-10 and IL-18, respectively, synergize to facilitate regression of established tumors. These observations also suggest the potential use of double-recombinant adenoviral vectors expressing chemokines and immunomodulatory cytokines in cancer gene therapy.     

Enhanced HER-2/neu-specific antitumor immunity by cotransduction of mouse dendritic cells with two genes encoding HER-2/neu and alpha tumor necrosis factor

The present study uses an in vivo murine tumor model expressing the human HER-2/neu antigen to evaluate the potential vaccine using dendritic cells (DCs) infected with adenovirus AdVHER-2. We first investigated whether infected DCs (DC(HER-2)) engineered to express HER-2/neu could induce HER-2/neu-specific immune responses. Our data showed that (i) AdVHER2-infected DC(HER-2) expressed HER-2/neu by Western blot and flow cytometric analysis, and (ii) vaccination of mice with DC(HER-2) induced HER-2/neu-specific cytotoxic T-lymphocyte (CTL) responses, but protected only 25% of vaccinated mice from challenge of 3 x 10(5) MCA26/HER-2 tumor cells. Further, to enhance the efficacy of DC(HER-2) vaccine, we coinfected DCs with both AdVHER-2 and AdVTNF-alpha. The infected DCs (DC(HER-2/TNF-alpha)) displayed the expression of both HER-2/neu and TNF-alpha by flow cytometric and ELISA analysis. We next investigated whether DC(HER-2/TNF-alpha) could induce stronger HER-2/neu-specific immune responses. We found that DC(HER-2/TNF-alpha) displayed up-regulation of immunologically important CD40, CD86, and ICAM-I molecules compared with DC(HER-2), indicating that the former ones are more mature forms of DCs. Vaccination of DC(HER-2/TNF-alpha) induced stronger allogeneic T-cell proliferation and 36% enhanced HER-2/neu-specific T-cell responses in vitro than DC(HER-2) cells. More importantly, it stimulated the significant anti-HER-2/neu immunity in vivo, which protected 8/8 mice from challenge of 3 x 10(5) MCA26/HER-2 tumor cells. Therefore, DCs genetically engineered to express both the tumor antigen and cytokines such as TNF-alpha as an immunoadjuvant are likely to represent a new direction in DC vaccine of cancer.