The foveas of subjects with a history of mild ROP have significant structural abnormalities that are probably a consequence of perturbations of neurovascular development.
Controlling metastases remains a critical problem in cancer biology. Within the peritoneal cavity, omental tissue is a common site for metastatic disease arising from intraperitoneal tumors; however, it is unknown why this tissue is so favorable for metastatic tumor growth. Using five different tumor cell lines in three different strains of mice, we found that the omentum was a major site of metastases growth for intraperitoneal tumors. Furthermore, initial attachment and subsequent growth were limited to specific sites within the omentum, consisting of organized aggregates of immune cells. These immune aggregates contained a complex network of capillaries exhibiting a high vascular density, which appear to contribute to the survival of metastatic cells. We found that the vasculature within these aggregates contained CD105؉ vessels and vascular sprouts, both indicators of active angiogenesis. A subset of mesothelial cells situated atop the immune aggregates was found to be hypoxic, and a similar proportion was observed to secrete vascular endothelial growth factor-A. These data provide a physiological mechanism by which metastatic tumor cells preferentially grow at sites rich in proangiogenic vessels, apparently stimulated by angiogenic factors produced by mesothelial cells. These sites provide metastatic cells with a microenvironment highly conducive to survival and subsequent growth.
The in vitro susceptibility of pathogenic Candida species to the photodynamic effects of the clinically approved photosensitizing agent Photofrin was examined. Internalization of Photofrin by Candida was confirmed by confocal fluorescence microscopy, and the degree of uptake was dependent on incubation concentration. Uptake of Photofrin by Candida and subsequent sensitivity to irradiation was influenced by culture conditions. Photofrin uptake was poor in C. albicans blastoconidia grown in nutrient broth. However, conversion of blastoconidia to filamentous forms by incubation in defined tissue culture medium resulted in substantial Photofrin uptake. Under conditions where Photofrin was effectively taken up by Candida, irradiated organisms were damaged in a drug dose-and light-dependent manner. Uptake of Photofrin was not inhibited by azide, indicating that the mechanism of uptake was not dependent on energy provided via electron transport. Fungal damage induced by Photofrin-mediated photodynamic therapy (PDT) was determined by evaluation of metabolic activity after irradiation. A strain of C. glabrata took up Photofrin poorly and was resistant to killing after irradiation. In contrast, two different strains of C. albicans displayed comparable levels of sensitivity to PDT. Furthermore, a reference strain of C. krusei that is relatively resistant to fluconazole compared to C. albicans was equally sensitive to C. albicans at Photofrin concentrations of >3 g/ml. The results indicate that photodynamic therapy may be a useful adjunct or alternative to current anti-Candida therapeutic modalities, particularly for superficial infections on surfaces amenable to illumination.Photodynamic therapy (PDT) is a process in which cells are treated with an agent that makes them susceptible to killing by exposure to light. These agents, called photosensitizers, are generally macrocyclic compounds that exhibit no or minimal inherent toxicity but result in the generation of cytotoxic reactive oxygen species when excitation occurs with light of the appropriate wavelength. PDT has been applied most extensively in the treatment of neoplasms and shows promise as a novel therapy for some non-neoplastic disorders (4, 11). Photofrin is a photosensitizer that has been the subject of intensive investigation (4). Derived from acid treatment of hematoporphyrin, this compound has been approved by the U.S. Food and Drug Administration for the treatment of endobronchial and esophageal tumors (11) and is currently in clinical trials for several other indications.Although PDT is becoming established as a treatment modality to augment conventional chemotherapy and radiation in the oncologic literature, much less is known about the effects of photosensitizers on fungi of medical importance. Candida species have become increasingly prevalent as causes of both mucocutaneous and systemic infection in immunocompromised patients (3). Moreover, resistance of Candida to traditional antifungals such as fluconazole is increasing, with some species such as Cand...
Angularly resolved light scattering measurements were performed on suspensions of EMT6 cells and on mitochondria isolated from rabbit liver. Mie theory analysis of the scattering from intact cells indicated that mitochondrial-sized organelles dominated scattering in the range 5-90 degrees . This interpretation was supported by the analysis of scattering from isolated mitochondria. Intact cells were subjected to oxidative stress by photodynamic insult. After 3 h of incubation in the heme precursor aminolevulinic acid hexylester, EMT6 cells accumulated abundant protoporphyrin IX, an endogenous photosensitizer formed in mitochondria. Irradiation of aminolevulinic acid/protoporphyrin IX-sensitized cells with 10 J cm(-2) of 514 nm light led to pronounced changes in angularly resolved light scattering consistent with mitochondrial swelling. Electron microscopy of similarly treated EMT6 cell monolayers showed significant changes in mitochondrial morphology, which included distension of the outer unit membrane and bloating of the internal mitochondrial compartment. Informed by these electron microscopy results, we implemented a coated sphere model to interpret the scattering from intact cells subjected to oxidative stress. The coated sphere interpretation was compatible with the scattering measurements from these cells, whereas simpler Mie theory models based on homogenous swelling were dramatically unsuccessful. Thus, in this system, angularly resolved light scattering reports oxidative-stress-induced changes in mitochondrial morphology.
A retinal imaging instrument that integrates adaptive optics (AO), scanning laser ophthalmoscopy (SLO), and retinal tracking components was built and tested. The system uses a Hartmann-Shack wave-front sensor (HS-WS) and MEMS-based deformable mirror (DM) for AO-correction of high-resolution, confocal SLO images. The system includes a wide-field line-scanning laser ophthalmoscope for easy orientation of the high-magnification SLO raster. The AO system corrected ocular aberrations to <0.1 μm RMS wave-front error. An active retinal tracking with custom processing board sensed and corrected eye motion with a bandwidth exceeding 1 kHz. We demonstrate tracking accuracy down to 6 μm RMS for some subjects (typically performance: 10-15 μm RMS). The system has the potential to become an important tool to clinicians and researchers for vision studies and the early detection and treatment of retinal diseases.
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