Research collaboration in Tehran University of Medical Sciences: two decades after integration

Background  

In 1985 medical schools were integrated into the Ministry of Health, and the Ministry of Health and Medical Education was created in Iran. Under this infrastructure education, research and service provision are unified, and it is expected that collaboration between researchers and decision makers become easier in such an integrated context.     

A unified framework for clustering and quantitative analysis of white matter fiber tracts

We present a novel approach for joint clustering and point-by-point mapping of white matter fiber pathways. Knowledge of the point correspondence along the fiber pathways is not only necessary for accurate clustering of the trajectories into fiber bundles, but also crucial for any tract-oriented quantitative analysis. We employ an expectation-maximization (EM) algorithm to cluster the trajectories in a gamma mixture model context. The result of clustering is the probabilistic assignment of the fiber trajectories to each cluster, an estimate of the cluster parameters, i.e. spatial mean and variance, and point correspondences. The fiber bundles are modeled by the mean trajectory and its spatial variation. Point-by-point correspondence of the trajectories within a bundle is obtained by constructing a distance map and a label map from each cluster center at every iteration of the EM algorithm. This offers a time-efficient alternative to pairwise curve matching of all trajectories with respect to each cluster center. The proposed method has the potential to benefit from an anatomical atlas of fiber tracts by incorporating it as prior information in the EM algorithm. The algorithm is also capable of handling outliers in a principled way. The presented results confirm the efficiency and effectiveness of the proposed framework for quantitative analysis of diffusion tensor MRI.     

Therapeutic strategies against inflammation and bone loss associated with osteomyelitis

Despite current treatment strategies, osteomyelitis is often refractory and recurrent. The bacteria responsible for osteomyelitis can invade bone-forming osteoblasts, which are active participants in the generation of damaging inflammation and bone loss at sites of infection. Therefore, strategies promoting cell-mediated immune responses while limiting inflammation are required for the treatment of chronic bone infections. This review describes the mechanisms utilized by resident bone cells to perceive bacteria, recruit leukocytes to sites of infection and promote osteoclast-mediated bone destruction, as well as novel targets for the therapeutic intervention of these processes.     

A good manufacturing practice method to ex vivo expand natural killer cells for clinical use

BackgroundGreat interest has been raised recently by the design of new adoptive immunotherapeutic strategies based on the in vivo infusion of ex vivo-expanded and activated natural killer (NK) cells. The development of good manufacturing practice (GMP) methods for the efficient production of fully functional NK cells is mandatory for clinical application.ResultsNK-cell populations expanded on average 15.7±4.7 fold by day 14, with a viability of 96% ±0.5. At the end of the incubation period, 97% ±1.1 of the expanded population was CD56⁺ NK cells; these effector cells showed significant up-regulation of the activating receptors NKG2D and DNAM-1. Functional tests demonstrated that expanded NK cells are fully functional with no difference whether tested before cryopreservation or after thawing.DiscussionThese data provide the basis for developing new NK-cell-based immunotherapeutic strategies for the treatment of patients with cancer.     

Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms

Podoplanin (PDPN) is a unique transmembrane receptor that promotes tumor cell motility. Indeed, PDPN may serve as a chemotherapeutic target for primary and metastatic cancer cells, particularly oral squamous cell carcinoma (OSCC) cells that cause most oral cancers. Here, we studied how a monoclonal antibody (NZ-1) and lectin (MASL) that target PDPN affect human OSCC cell motility and viability. Both reagents inhibited the migration of PDPN expressing OSCC cells at nanomolar concentrations before inhibiting cell viability at micromolar concentrations. In addition, both reagents induced mitochondrial membrane permeability transition to kill OSCC cells that express PDPN by caspase independent nonapoptotic necrosis. Furthermore, MASL displayed a surprisingly robust ability to target PDPN on OSCC cells within minutes of exposure, and significantly inhibited human OSCC dissemination in zebrafish embryos. Moreover, we report that human OSCC cells formed tumors that expressed PDPN in mice, and induced PDPN expression in infiltrating host murine cancer associated fibroblasts. Taken together, these data suggest that antibodies and lectins may be utilized to combat OSCC and other cancers that express PDPN.     

Oxygen tension and gradient measurements in the retinal microvasculature of rats

Background  

Oxygen delivery from the retinal vasculature plays a crucial role in maintaining normal retinal metabolic function. Therefore, measurements of retinal vascular oxygen tension (PO₂) and PO₂ longitudinal gradients (gPO₂) along retinal blood vessels may help gain fundamental knowledge of retinal physiology and pathological processes.