The molecular basis of pathogen clone emergence is relatively poorly understood. Acquisition of a bacteriophage encoding a previously unknown secreted phospholipase A 2 (designated SlaA) has been implicated in the rapid emergence in the mid-1980s of a new hypervirulent clone of serotype M3 group A Streptococcus. Although several lines of circumstantial evidence suggest that SlaA is a virulence factor, this issue has not been addressed experimentally. We found that an isogenic ⌬slaA mutant strain was significantly impaired in ability to adhere to and kill human epithelial cells compared with the wild-type parental strain. The mutant strain was less virulent for mice than the wild-type strain, and immunization with purified SlaA significantly protected mice from invasive disease. Importantly, the mutant strain was significantly attenuated for colonization in a monkey model of pharyngitis. We conclude that transductional acquisition of the ability of a GAS strain to produce SlaA enhanced the spread and virulence of the serotype M3 precursor strain. Hence, these studies identified a crucial molecular event underlying the evolution, rapid emergence, and widespread dissemination of unusually severe human infections caused by a distinct bacterial clone.bacteria ͉ Group A Streptococcus ͉ Streptococcus pyogenes

The organ systems affected in descending order of number of neoplasms were hematopoietic organs (n = 101, 28%), urogenital tract (n = 78, 21%), integument (n = 43, 12%), alimentary tract (n = 43, 12%), endocrine organs (n = 40, 11%), nervous system (n = 33, 9%), musculoskeletal system (n = 5, 1%), and respiratory system (n = 4, 1%). Malignant cases numbered 171 (47%); 192 (53%) cases were benign.

To evaluate the ability of cultured mesenchymal stem cells (MSC) to repair physeal defects, MSC-matrix constructs with 5% gelatin (group A), 10% gelatinlGelfoam (Pharmacia, Peapack, NJ) (group B), and MSC grown in the presence of TGF+ with Gelfoam (group C) were implanted in proximal tibia1 physeal defects created in 20 immature rabbits. Control groups (untreated partial defect and partial defect treated with Gelfoam) showed bony bar formation with varus deformities of 30" and 28", respectively. Group A had an average 23" varus deformity with bony bridge formation, and group B had mild varus angulation (average 14") of the proximal tibia. In group C, there was no significant varus deformity (average 9"), and histologic examination showed that some of the columnation areas interspersed with chondrocytes were irregularly arranged in the matrix. These findings suggest that repair of physeal defects can be enhanced by the implantation of MSC cultured with TGF-p3.

The objective of tissue engineering (TE) is to create functional replacements for various tissues; the mechanical properties of these engineered constructs are critical to their function. Several techniques have been developed for the measurement of the mechanical properties of tissues and organs; however, current methods are destructive. The field of TE will benefit immensely if biomechanical models developed by these techniques could be combined with existing imaging modalities to enable noninvasive, dynamic assessment of mechanical properties during tissue growth. Specifically, MR elastography (MRE), which is based on the synchronization of a mechanical actuator with a phase contrast imaging pulse sequence, has the capacity to measure tissue strain generated by sonic cyclic displacement. The captured displacement is presented in shear wave images from which the complex shear moduli can be extracted or simplified by a direct measure, termed the shear stiffness. MRE has been extended to the microscopic scale, combining clinical MRE with high-field magnets, stronger magnetic field gradients and smaller, more sensitive, radiofrequency coils, enabling the interrogation of smaller samples, such as tissue-engineered constructs. The following topics are presented in this article: (i) current mechanical measurement techniques and their limitations in TE; (ii) a description of the MRE system, MRE theory and how it can be applied for the measurement of mechanical properties of tissue-engineered constructs; (iii) a summary of in vitro MRE work for the monitoring of osteogenic and adipogenic tissues originating from human adult mesenchymal stem cells (MSCs); (iv) preliminary in vivo studies of MRE of tissues originating from mouse MSCs implanted subcutaneously in immunodeficient mice with an emphasis on in vivo MRE challenges; (v) future directions to resolve current issues with in vivo MRE in the context of how to improve the future role of MRE in TE.